FN Thomson Reuters Web of Science™ VR 1.0 PT J AU FARSHID, M NEDJAR, S MITCHELL, F BISWAS, R AF FARSHID, M NEDJAR, S MITCHELL, F BISWAS, R TI ALTERED EXPRESSION OF RB PROTEIN IN HEP G2 CELLS TRANSFECTED WITH CLONED HEPATITIS-B VIRUS-X GENE SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,HEPATITIS LAB,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1993 VL 18 IS 4 BP A199 EP A199 DI 10.1016/0270-9139(93)92324-S PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LY995 UT WOS:A1993LY99500570 ER PT J AU MAHANEY, K DIBISCEGLIE, AM HOOFNAGLE, JH SALLIE, R AF MAHANEY, K DIBISCEGLIE, AM HOOFNAGLE, JH SALLIE, R TI GENOMIC VARIABILITY OF THE HEPATITIS-C VIRUS (HCV) - DEVELOPMENT OF MUTATIONS DURING ANTIVIRAL THERAPY SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. US FDA,HEPATITIS RES LAB,BETHESDA,MD 20014. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1993 VL 18 IS 4 BP A92 EP A92 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LY995 UT WOS:A1993LY99500144 ER PT J AU NEDJAR, S MITCHELL, F ZHAI, M BISWAS, R AF NEDJAR, S MITCHELL, F ZHAI, M BISWAS, R TI SEQUENTIAL DETECTION OF HCV-RNA, ALT AND ANTIBODIES IN SERUM SAMPLES OF HEPATITIS-C VIRUS-INFECTED CHIMPANZEES SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,HEPATITIS LAB,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1993 VL 18 IS 4 BP A246 EP A246 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LY995 UT WOS:A1993LY99500753 ER PT J AU RIEPENHOFFTALTY, M ROSSI, T GOUVEA V EVANS, MJ AF RIEPENHOFFTALTY, M ROSSI, T GOUVEA, V EVANS, MJ TI EXTRAHEPATIC BILIARY ATRESIA (EHBA) IN HUMAN INFANTS ASSOCIATED WITH GROUP C ROTAVIRUS SO HEPATOLOGY LA English DT Meeting Abstract C1 SUNY Buffalo, CHILDRENS HOSP BUFFALO, DEPT PEDIAT, BUFFALO, NY 14260 USA. US FDA, DIV MICROBIOL, WASHINGTON, DC 20204 USA. NEW YORK STATE DEPT HLTH, ROSWELL PK MEM INST, DEPT NEUROL, BUFFALO, NY 14263 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1993 VL 18 IS 4 BP A98 EP A98 DI 10.1016/0270-9139(93)91922-F PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LY995 UT WOS:A1993LY99500168 ER PT J AU SALLIE, R CHIA, SC HOOFNAGLE, J DIBISCEGLIE, AM FEINSTONE, SM AF SALLIE, R CHIA, SC HOOFNAGLE, J DIBISCEGLIE, AM FEINSTONE, SM TI THE 5' END OF HCV - CHARACTERIZATION BY END-TO-END RNA LIGATION-MEDIATED POLYMERASE CHAIN-REACTION SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD 20892. US FDA,CBER,HEPATITIS LAB,BETHESDA,MD 20205. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1993 VL 18 IS 4 BP A78 EP A78 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LY995 UT WOS:A1993LY99500085 ER PT J AU GUNTER, KC KHAN, AS NOGUCHI, PD AF GUNTER, KC KHAN, AS NOGUCHI, PD TI THE SAFETY OF RETROVIRAL VECTORS SO HUMAN GENE THERAPY LA English DT Article ID PRIMATES; VIRUS C1 US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,OFF THERAPEUT RES & REV,ROCKVILLE,MD 20852. US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,OFF VACCINES RES & REVIEW,ROCKVILLE,MD 20852. NR 6 TC 35 Z9 36 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 OCT PY 1993 VL 4 IS 5 BP 643 EP 645 DI 10.1089/hum.1993.4.5-643 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA MD263 UT WOS:A1993MD26300011 PM 8280802 ER PT J AU ANSHER, S THOMPSON, W BRIDGEWATER, J SNOY, P AF ANSHER, S THOMPSON, W BRIDGEWATER, J SNOY, P TI PERTUSSIS TOXIN-INDUCED ALTERATIONS OF MURINE HEPATIC DRUG-METABOLISM FOLLOWING ADMINISTRATION OF DIPHTHERIA AND TETANUS TOXOIDS AND PERTUSSIS-VACCINE ADSORBED SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INFLUENZA VACCINATION; BORDETELLA-PERTUSSIS; WHOOPING-COUGH; CYTOCHROME-P-450; ENDOTOXIN; CHILDREN; MICE; DEPRESSION; TOXICITY AB Administration of pertussis toxin (PT) in combination with diphtheria and tetanus toxoids adsorbed (DT vaccine) or with acellular pertussis vaccine adsorbed and diphtheria and tetanus toxoids (APDT) elicits dose- and time-dependent alterations in hepatic drug metabolism in mice. Cytochrome P-450 (P-450) levels were inhibited more than 50% at 7 days following a single injection of PT mixed with either vaccine. When combined with DT vaccine, 125 ng of PT was required to produce this effect, while as little as 16 ng of PT combined with APDT vaccine inhibited P-450 levels. The inhibition of P450 levels is similar to that observed after a single injection of diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP). Alterations of P-450 levels were accompanied by increased activities of quinone reductase but not with changes in plasma interleukin-6 or tumor necrosis factor levels. Other Bordetella pertussis virulence factors, such as filamentous hemagglutinin, fimbriae and pertactin, were also tested but had no significant effect on hepatic drug metabolism. Endotoxin or preparations containing endotoxin caused alterations in hepatic drug metabolism within 24 h, concomitant with increased interleukin-6 and tumor necrosis factor levels, but these effects had resolved by 1 week. DTP vaccine and preparations containing PT caused a marked induction of gamma interferon coincident with the maximal inhibition of P-450 levels. This effect was not present with DT or APDT vaccine alone, nor with endotoxin or any combination of factors that did not contain PT. These results demonstrate that PT is a necessary component for the sustained effects of DTP vaccine on hepatic drug metabolism and suggest a role for gamma interferon in this process. C1 US FDA,CTR BIOLOG EVALUAT & RES,DIV PROD QUAL CONTROL,BETHESDA,MD 20205. RP ANSHER, S (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20205, USA. NR 32 TC 7 Z9 8 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 OCT PY 1993 VL 61 IS 10 BP 4240 EP 4247 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LZ264 UT WOS:A1993LZ26400032 PM 8406812 ER PT J AU HUNTLEY, JS HALL, AC SATHYAMOORTHY, V HALL, RH AF HUNTLEY, JS HALL, AC SATHYAMOORTHY, V HALL, RH TI CATION FLUX STUDIES OF THE LESION-INDUCED IN HUMAN ERYTHROCYTE-MEMBRANES BY THE THERMOSTABLE DIRECT HEMOLYSIN OF VIBRIO-PARAHAEMOLYTICUS SO INFECTION AND IMMUNITY LA English DT Article ID PSEUDOMONAS-AERUGINOSA; NUCLEOTIDE-SEQUENCE; RED-CELLS; GENE; PURIFICATION; PERMEABILITY; TRANSPORT; AGENTS AB Vibrio parahaemolyticus, an important agent of seafood-borne gastroenteritis, expresses several putative virulence factors that could account for the disease symptoms of infected humans, namely, diarrhea, nausea, and abdominal cramps. The pathogenicity of V. parahaemolyticus correlates well with the Kanagawa phenomenon (the hemolytic ability of strains grown on Wagatsuma blood agar), implicating the thermostable direct hemolysin (TDH) as the predominant toxin responsible for pathogenicity. TDH-induced hemolysis could be inhibited by the addition of the osmolyte sorbitol to the extracellular solution, supporting the hypothesis that hemolysis occurs through colloid osmosis secondary to an increase in the cation permeability of the membrane. The effect of TDH on cation permeability was investigated by measuring K+ (congener, Rb-86+) influx into human erythrocytes in which the endogenous cation transporters had been blocked (by use of ouabain, bumetanide, and nitrendipine). TDH increased K+ influx into these cells; this increase was rapid in onset and constant in magnitude, suggesting a direct action by TDH on the membrane. The kinetics of leak generation were examined; the relationship between counts accumulated and hematocrit indicated that the TDH-induced lesion is multihit in nature. TDH-induced K+ influx was sensitive to Zn2+. Time courses of hemolysis in isosmotic solutions of monovalent cation chlorides were used to obtain the selectivity series for the TDH-induced leak: Cs+ > Li+ > K+ > Rb+ > Na+. Both the Zn2+ sensitivity and this selectivity series were obtained for crude culture supernatants, suggesting that TDH is the predominant leak-inducing agent. Thus, we have identified several features of the TDH-induced leak likely to be important in the diarrhetic action of V. parahaemolyticus in the human intestine. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV VIRULENCE ASSESSMENT,WASHINGTON,DC 20204. RP HUNTLEY, JS (reprint author), UNIV OXFORD,PHYSIOL LAB,PARKS RD,OXFORD OX1 3PT,ENGLAND. OI Huntley, James/0000-0003-1826-4007 FU Wellcome Trust NR 47 TC 14 Z9 14 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1993 VL 61 IS 10 BP 4326 EP 4332 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LZ264 UT WOS:A1993LZ26400043 PM 8406820 ER PT J AU JESSOP, JJ HENRY, SL HOFFMAN, T AF JESSOP, JJ HENRY, SL HOFFMAN, T TI EFFECTS OF SERINE-PROTEASE INHIBITOR, TAME, ON IL-1-BETA IN LPS-STIMULATED HUMAN MONOCYTES - RELATIONSHIP BETWEEN SYNTHESIS AND RELEASE OF A 33-KDA PRECURSOR AND THE 17-KDA BIOLOGICALLY-ACTIVE SPECIES SO INFLAMMATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; CULTURED HUMAN-MONOCYTES; HUMAN MONONUCLEAR-CELLS; FC-GAMMA-RII; KINASE-C; IL-1 RECEPTOR; FACTOR-ALPHA; SECRETION; EXPRESSION AB LPS stimulation of human monocytes in vitro induced release of the 17-kDa mature IL-1beta (mIL-1beta) but did not result in release of precursor IL-1beta (pIL-1beta). In contrast, the presence of a serine protease inhibitor, Nalpha-(p-toluene sulfonyl)-L-arginine methyl ester (TAME; 10 mM) for 6 or 18 h was associated with the LPS-stimulated release of the 33-kDa pIL-1beta as well. These effects were initially discerned from observations that the fraction of the total IL-1beta produced (as detected by ELISA) that was released from monocytes increased in the presence of TAME, and immunoblot assays confirmed that this fraction was predominantly 33-kDa IL-1beta. A global decrease in monocyte protein synthesis was also observed after prolonged (18-h) exposure to TAME and was associated with a decrease in IL-1beta synthesis, predominantly affecting 31-kDa pIL-1beta, and a dose-dependent inhibition of TNF-alpha production. Parallel examination of lactate dehydrogenase (LDH) release indicated that pIL-1beta release was unrelated to cell lysis. These results demonstrate that TAME-inhibitable serine proteases are probably involved in the production and eventual proteolysis of the 33-kDa pIL-1beta in situ but are probably not mechanistically related to either maturation of the IL-1beta molecule or signaling of IL-1beta release. IL-1beta release appears to be dependent on the amount of total IL-1beta synthesized. Serine proteolysis may constitute a degradative pathway for excess precursor, which, if interfered with, could result in release of the higher-molecular-weight forms of IL-1beta. RP JESSOP, JJ (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV MONOCLONAL ANTIBODIES,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 1 Z9 1 U1 0 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0360-3997 J9 INFLAMMATION JI Inflammation PD OCT PY 1993 VL 17 IS 5 BP 613 EP 631 DI 10.1007/BF00914198 PG 19 WC Cell Biology; Immunology SC Cell Biology; Immunology GA LU842 UT WOS:A1993LU84200008 PM 8225567 ER PT J AU HARASAWA, R IMADA, Y KOTANI, H KOSHIMIZU, K BARILE, MF AF HARASAWA, R IMADA, Y KOTANI, H KOSHIMIZU, K BARILE, MF TI UREAPLASMA-CANIGENITALIUM SP-NOV, ISOLATED FROM DOGS SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID T-MYCOPLASMAS AB Ureaplasma strains isolated from dogs (Canis familiaris) were characterized and compared with the type strains of five previously described species of the genus Ureaplasma, Ureaplasma urealyticum (isolated from humans), Ureaplasma diversum (isolated from cattle), Ureaplasma gallorale (isolated from chickens), Ureaplasma cati (isolated from cats), and Ureaplasma felinum (isolated from cats). The canine strains hydrolyzed urea but not arginine or glucose, were membrane bound, lacked a cell wall, passed through 450-nm-pore-size membrane filters, required cholesterol for growth, and formed minute colonies (diameter, 20 to 140 mum) on agar medium. These canine ureaplasma strains have been reported to be members of four serovars. The four serovars of canine strains fell into a single group on the basis of their genomic properties, as determined by DNA-DNA hybridization. On the basis of these findings, we propose that ureaplasmas with these characteristics belong to a new species, Ureaplasma canigenitalium, with strain D6P-C (= ATCC 51252) as the type strain. C1 NATL INST ANIM HLTH,TSUKUBA,IBARAKI 305,JAPAN. KAGOSHIMA UNIV,FAC AGR,DEPT VET MICROBIOL,KAGOSHIMA 890,JAPAN. GENET THERAPY INC,DEPT SCALE UP,GAITHERSBURG,MD 20878. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP HARASAWA, R (reprint author), UNIV TOKYO,FAC MED,ANIM CTR BIOMED RES,BUNKYO KU,TOKYO 113,JAPAN. NR 29 TC 8 Z9 8 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1993 VL 43 IS 4 BP 640 EP 644 PG 5 WC Microbiology SC Microbiology GA MC210 UT WOS:A1993MC21000002 PM 8240947 ER PT J AU REICHMAN, BS SEIDMAN, AD CROWN, JPA HEELAN, R HAKES, TB LEBWOHL, DE GILEWSKI, TA SURBONE, A CURRIE, V HUDIS, CA YAO, TJ KLECKER, R JAMISDOW, C COLLINS, J QUINLIVAN, S BERKERY, R TOOMASI, F CANETTA, R FISHERMAN, J ARBUCK, S NORTON, L AF REICHMAN, BS SEIDMAN, AD CROWN, JPA HEELAN, R HAKES, TB LEBWOHL, DE GILEWSKI, TA SURBONE, A CURRIE, V HUDIS, CA YAO, TJ KLECKER, R JAMISDOW, C COLLINS, J QUINLIVAN, S BERKERY, R TOOMASI, F CANETTA, R FISHERMAN, J ARBUCK, S NORTON, L TI PACLITAXEL AND RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR AS INITIAL CHEMOTHERAPY FOR METASTATIC BREAST-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-II TRIAL; TAXOL; AGENT; CELLS; RESISTANCE; TUBULIN; THERAPY; REINDUCTION; MECHANISM; CISPLATIN C1 MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,BREAST & GYNECOL CANC MED SERV,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT MED IMAGING,NEW YORK,NY 10021. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,WALLINGFORD,CT. NCI,DIV CANC THERAPY,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. US FDA,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. MEM SLOAN KETTERING CANC CTR,DEPT EPIDEMIOL & BIOSTAT,NEW YORK,NY 10021. FU NCI NIH HHS [1-CM07311, CA-09207-14] NR 32 TC 260 Z9 261 U1 0 U2 7 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 OCT PY 1993 VL 11 IS 10 BP 1943 EP 1951 PG 9 WC Oncology SC Oncology GA MC299 UT WOS:A1993MC29900017 PM 7691998 ER PT J AU JOHNSON, J TANNER, LA AF JOHNSON, J TANNER, LA TI POSTMARKETING SURVEILLANCE - CURRICULUM FOR THE CLINICAL PHARMACOLOGIST .1. POSTMARKETING SURVEILLANCE WITHIN THE CONTINUUM OF THE DRUG APPROVAL PROCESS SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID INVESTIGATIONAL DRUGS AB This series of two articles on postmarketing safety surveillance has been developed for use in training clinical pharmacologists. It provides a basic overview useful to clinical pharmacologists in a range of occupational functions. These reports can be used as the basis for a lecture or as background reading material for establishing a unit on postmarketing surveillance. For teaching rounds, multiple illustrations and summary tables have been included. These can readily be made into 35-mm slides or transparencies. Table I outlines the curriculum on postmarketing surveillance for the clinical pharmacologist. The first article describes postmarketing surveillance within the continuum of the drug approval process. The relationship of clinical trials to safety surveillance after drug approval are reviewed. The importance of spontaneous adverse drug experience reporting also is discussed. The second article focuses on the regulatory aspects of postmarketing surveillance and discusses the FDA's (Food and Drug Administration) Spontaneous Reporting System. The two types of adverse experience reports in the Spontaneous Reporting System are described: reports voluntarily submitted by health care providers and others, and reports manufacturers are required by regulation to submit. The clinical pharmacologist's role in postmarketing surveillance is defined. RP JOHNSON, J (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV EPIDEMIOL,HFD-730,ROOM 15B-31,ROCKVILLE,MD 20857, USA. NR 11 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD OCT PY 1993 VL 33 IS 10 BP 904 EP 911 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MA786 UT WOS:A1993MA78600002 PM 8227459 ER PT J AU CHU, CC MAX, EE PAUL, WE AF CHU, CC MAX, EE PAUL, WE TI DNA REARRANGEMENT CAN ACCOUNT FOR IN-VITRO SWITCHING TO IGG1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID POLYMERASE CHAIN-REACTION; B-LYMPHOBLASTOID CELLS; TRANS-MESSENGER RNA; MONOCLONAL-ANTIBODIES; CIRCULAR DNA; HEAVY-CHAINS; IGH LOCI; RECOMBINATION; ISOTYPE; EXPRESSION AB During immune responses, B lymphocytes may switch from the expression of immunoglobulin M (IgM) to the expression of another isotype (e.g., IgG, IgE, IgA). In stable hybridomas and myelomas expressing a ''switched'' (S) isotype, DNA deletions between Smu and a ''downstream' S region (S region recombination) have been found. In primary B cells, studies of the molecular basis of switching have been limited by the ability to sensitively quantitate the amount of DNA deletion; such studies would be of interest because other nondeletional mechanisms (trans-splicing, alternative processing of a long transcript) have been proposed to account for isotype switching in certain circumstances. We have applied the digestion-circularization polymerase chain reaction (DC-PCR) technique to measure the amount of S region recombination that occurs in the course of class switching in primary B lymphocytes. Resting B cells were cultured in lipopolysaccharide (LPS) and interleukin 4 (IL-4) to stimulate switching to IgG1. These cells begin to express membrane IgG1 at day 2.5 of culture and reach maximum expression by day 4.5. DNA was prepared from cultured cells and analyzed for Smu-Sgamma1 rearrangement by DC-PCR. Chimeric switch regions, indicating Smu-Sgamma1 recombination, were detected in amounts that, in most cases, correlated with surface expression. Furthermore, when cells were sorted on the basis of surface IgG1 expression, a mean of at least one Smu-Sgamma1 rearrangement per cell was seen in five out of seven experiments. In general, the IgG1+ cells obtained at 4.5 and 5.5 d of culture had close to 2 Smu-Sgamma1 rearrangements per cell. In IgG1- cells, Smu-Sgamma1 rearrangements were detectable, but at frequencies substantially lower that in IgG1+ cells. Thus, these results indicate that DNA deletion accompanies class switching in normal B cells stimulated with LPS and IL-4. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 31 TC 24 Z9 26 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 OCT 1 PY 1993 VL 178 IS 4 BP 1381 EP 1390 DI 10.1084/jem.178.4.1381 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LY323 UT WOS:A1993LY32300022 PM 8376941 ER PT J AU ZHANG, PF MARCUSSEKURA, CJ AF ZHANG, PF MARCUSSEKURA, CJ TI CONFORMATION-DEPENDENT RECOGNITION OF BACULOVIRUS-EXPRESSED EPSTEIN-BARR VIRUS-GP350 BY A PANEL OF MONOCLONAL-ANTIBODIES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID MAJOR ENVELOPE GLYCOPROTEINS; VIRUS MEMBRANE-ANTIGENS; HUMAN LYMPHOCYTES-B; T-CELL CLONES; NEUTRALIZING ANTIBODIES; RECEPTOR CR-2; LINKED OLIGOSACCHARIDES; COTTONTOP TAMARINS; STRAIN DIFFERENCES; ESCHERICHIA-COLI AB The Epstein-Barr virus (EBV) major membrane protein, gp350, induces antibodies that neutralize virus infectivity in vitro and is a potential candidate for an EBV vaccine. Full-length EBV gp350 and five protein fragments, encompassing the entire protein sequence, were generated in a baculovirus expression system. The recombinant proteins were analysed using a panel of 14 monoclonal antibodies (MAbs) (13 prepared against native gp350 derived from virus-producing cells and one prepared against an Escherichia coli recombinant protein). All 14 MAbs, including a virus-neutralizing antibody, reacted with the full-length recombinant gp350 in a dot blot immunoassay, but only four of the 14 MAbs reacted with polypeptides expressed by the five subclones. indicating that the full-length protein, but not the protein fragments. was antigenically similar to native gp350. Treatment of the six recombinant proteins with peptide-N-glycosidase F (PNGase F) indicated that the full-length gp350 protein and the N-terminal fragment were glycosylated and that the four internally initiated polypeptides were not glycosylated. PNGase F treatment of the full-length glycosylated gp350 did not eliminate its reactivity with all of the 10 MAbs examined (including the neutralizing MAb) in a dot blot immunoassay; however, denatured glycosylated gp350 lost reactivity with all but four of the 14 MAbs when analysed by either dot blot or Western blot immunoassay. The data suggest that conformational epitopes are more important in recognition of gp350 by this panel of MAbs than glycosylation sites, and that the epitope on gp350 recognized by the neutralizing MAb is conformation- and not glycosylation-dependent. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,8800 ROCKVILLE PIKE,29A,3B-05 HFM457,ROCKVILLE,MD 20892. NR 49 TC 5 Z9 7 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD OCT PY 1993 VL 74 BP 2171 EP 2179 DI 10.1099/0022-1317-74-10-2171 PN 10 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA MA912 UT WOS:A1993MA91200016 PM 7691988 ER PT J AU VINCENT, PG AF VINCENT, PG TI ENVIRONMENTAL ASSESSMENT - US REQUIREMENTS IN NEW DRUG APPLICATIONS SO JOURNAL OF HAZARDOUS MATERIALS LA English DT Article; Proceedings Paper CT SYMP ON THE ROLE OF ENVIRONMENTAL ( ECOLOGICAL ) ASSESSMENT IN THE MANAGEMENT OF CHEMICAL POLLUTION, AT THE 204TH NATIONAL MEETING OF AMERICAN-CHEMICAL-SOC CY AUG 26-28, 1992 CL WASHINGTON, DC SP AMER CHEM SOC AB The Food and Drug Administration (FDA), under the Federal Food, Drug and Cosmetic (FD&C) Act and other public health statutes, is responsible for ensuring that human drugs are safe and effective. FDA is able to carry out its responsibilities by approving products before they are marketed, enforcing regulations, and taking necessary compliance actions when problems are identified. The National Environmental Policy Act (NEPA) provides FDA with supplementary authority to consider environmental factors in its decisionmaking. The role of the FDA Center for Drug Evaluation and Research in implementing NEPA is discussed. RP VINCENT, PG (reprint author), US FDA,CTR DRUG EVALUAT & RES,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3894 J9 J HAZARD MATER JI J. Hazard. Mater. PD OCT PY 1993 VL 35 IS 2 BP 211 EP 216 DI 10.1016/0304-3894(93)80006-2 PG 6 WC Engineering, Environmental; Engineering, Civil; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA ME951 UT WOS:A1993ME95100006 ER PT J AU HALEY, CJ MATHESON, JC EIRKSON, CE AF HALEY, CJ MATHESON, JC EIRKSON, CE TI REQUIREMENTS OF THE FDA FOR THE ENVIRONMENTAL ASSESSMENT OF ANIMAL HEALTH PRODUCTS SO JOURNAL OF HAZARDOUS MATERIALS LA English DT Article; Proceedings Paper CT SYMP ON THE ROLE OF ENVIRONMENTAL ( ECOLOGICAL ) ASSESSMENT IN THE MANAGEMENT OF CHEMICAL POLLUTION, AT THE 204TH NATIONAL MEETING OF AMERICAN-CHEMICAL-SOC CY AUG 26-28, 1992 CL WASHINGTON, DC SP AMER CHEM SOC ID CASE-HISTORIES; FAMPHUR AB Under the National Environmental Policy Act, the Center for Veterinary Medicine (the Center) at the Food and Drug Administration (FDA) assesses the potential environmental impact of a wide variety of animal health products. The FDA considers the manufacture, use, and disposal of these products. Environmental assessments of some products, for example, products that may cause indirect or secondary effects or products used in aquaculture, are particularly challenging. For actions not categorically excluded, sponsors of animal drug products must prepare either complete or abbreviated environmental assessments (EAs), depending upon the nature of the requested action. Complete EAs must address potential impacts caused by manufacture, use, and disposal of the product. Data from environmental testing are used in the development of complete EAs. Good Laboratory Practice (GLP) regulations and inspections are used to ensure the accuracy and data integrity of environmental information submitted for EAs. Potential impacts from manufacture of the product must be considered in both complete and abbreviated EAs. Good Manufacturing Practice (GMP) inspections are used to verify manufacturing information provided in environmental assessments. Efficient development of complete EAs requires making use of the tiered testing system, starting the environmental assessment early in the drug approval pro. cess, and communicating with the FDA Center for Veterinary Medicine when questions arise. RP HALEY, CJ (reprint author), US FDA,CTR VET MED,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3894 J9 J HAZARD MATER JI J. Hazard. Mater. PD OCT PY 1993 VL 35 IS 2 BP 217 EP 228 DI 10.1016/0304-3894(93)80007-3 PG 12 WC Engineering, Environmental; Engineering, Civil; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA ME951 UT WOS:A1993ME95100007 ER PT J AU ABDELHAMEED, MH CHEN, TM CHIOU, WL AF ABDELHAMEED, MH CHEN, TM CHIOU, WL TI INTRAHEPATIC DISTRIBUTION OF HYDROCHLOROTHIAZIDE AND QUINIDINE IN RATS - IMPLICATIONS IN PHARMACOKINETICS SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID ORGAN CLEARANCE APPROACH; HEPATIC DRUG CLEARANCE; PARTITION-COEFFICIENTS; PHYSIOLOGICAL APPROACH; BLOOD-FLOW; LIVER; TISSUE; ELIMINATION; MODEL; KINETICS AB The intrahepatic distributions of a nonmetabolized drug, hydrochlorothiazide (HCTZ) and a highly metabolized drug, quinidine (QD), were studied separately in five anesthetized rats during steady-state intravenous infusion. Liver samples (20-24) from various parts (0.1-0.2 g each) at the end of infusion were collected from each rat and analyzed for drug concentration by HPLC. The distribution of HCTZ in various macro regions appears quite ''homogeneous,'' with a CV of drug concentration for each rat ranging from 2.6 to 4.7% (grand mean, 3.7 +/- 0.8%), whereas that of QD seems less ''homogeneous,'' with a CV ranging from 8.5 to 28.3% (grand mean, 15.6 +/- 7.7%). The above results indicate that drugs that are not complicated by hepatic metabolism may tend to show more ''homogeneous'' distribution and those that are highly metabolized and/or known to strongly bind to hepatic tissue component(s) may show less ''homogeneous'' distribution. The results from the present QD study are in contrast with the general, much more heterogeneous distribution found in an isolated in situ perfusion study reported earlier. The implication of the present study in physiological pharmacokinetic and hepatic modeling is discussed. C1 UNIV ILLINOIS,COLL PHARM,DEPT PHARMACODYNAM,833 S WOOD ST,CHICAGO,IL 60612. US FDA,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857. NR 34 TC 1 Z9 1 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 OCT PY 1993 VL 82 IS 10 BP 992 EP 996 DI 10.1002/jps.2600821004 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA MA547 UT WOS:A1993MA54700003 PM 8254499 ER PT J AU WANG, JT SHIU, GK TING, OC VISWANATHAN, CT SKELLY, JP AF WANG, JT SHIU, GK TING, OC VISWANATHAN, CT SKELLY, JP TI EFFECTS OF HUMIDITY AND TEMPERATURE ON IN-VITRO DISSOLUTION OF CARBAMAZEPINE TABLETS SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID PHARMACOKINETICS; DIHYDRATE; FORMS AB The rate and extent of dissolution of various approved marketed carbamazepine (CBZ) tablets exposed to 33, 52, 75, and 97% relative humidities at both room temperature and 40-degrees-C, and saturated water vapor at room temperature were compared to fresh unstressed tablets. The dissolution data indicate that exposure of CBZ tablets to high humidity and temperature can have a profound effect on tablet disintegration and dissolution. The dissolution rates of some batches of CBZ products exposed to 97% humidity at 40-degrees-C or saturated water vapor at room temperature were drastically reduced in only 6-7 days. C1 US FDA,OFF GENER DRUGS,200 C ST,SOUTH WEST,WASHINGTON,DC 20204. US FDA,BIOPHARMACEUT RES BRANCH,WASHINGTON,DC 20204. US FDA,OFF RES RESOURCES,ROCKVILLE,MD 20857. NR 14 TC 11 Z9 11 U1 0 U2 9 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD OCT PY 1993 VL 82 IS 10 BP 1002 EP 1005 DI 10.1002/jps.2600821006 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA MA547 UT WOS:A1993MA54700005 PM 8254483 ER PT J AU LIPICKY, RJ PACKER, M AF LIPICKY, RJ PACKER, M TI ROLE OF SURROGATE END-POINTS IN THE EVALUATION OF DRUGS FOR HEART-FAILURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID EFFICACY; THERAPY; BLIND; TRIAL AB To be of clinical value in the treatment of heart failure, a drug must permit patients either to feel better or to live longer, or both. Yet, because the assessment of both quality and quantity of life is difficult, many investigators have proposed using alternate measures (namely, surrogate end points) that may indicate the probable effect of a drug on symptoms or survival but are not direct measures of clinical benefit. Surrogate end points are usually physiologic variables that are known to be statistically associated and are believed to be pathophysiologically related to the clinical outcome. Although the adoption of such surrogate end points would dramatically facilitate the evaluation of new drugs, experience to date has shown that the effect of a drug on a surrogate end point is not a reliable predictor of the clinical utility of the drug, usually because the assumption that the end point is pathophysiologically related to the outcome proves to be invalid. Consequently, the evaluation of the effect of a drug on a surrogate end point provides us with a hypothesis rather than data about the possible effect of a drug on clinical events; such a hypothesis can be tested in controlled clinical trials that directly measure the clinical benefit of the therapeutic intervention. In the area of heart failure, no surrogate end point currently exists that can be used in lieu of the direct assessment of a drug on symptoms or survival, ideally in the context of a placebo-controlled trial. C1 COLUMBIA UNIV COLL PHYS & SURG, DIV CIRCULATORY PHYSIOL, NEW YORK, NY USA. RP LIPICKY, RJ (reprint author), US FDA, CTR DRUG EVALUAT & RES, OFF DRUG EVALUAT 1, DIV CARDIORENAL DRUG PROD, ROCKVILLE, MD 20857 USA. NR 10 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1993 VL 22 IS 4 SU A BP A179 EP A184 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MR869 UT WOS:A1993MR86900034 PM 8376690 ER PT J AU PITT, B ELKAYAM, U GUYATT, GH LIPICKY, RJ PACKER, M YUSUF, S AF PITT, B ELKAYAM, U GUYATT, GH LIPICKY, RJ PACKER, M YUSUF, S TI MECHANISMS AND MANAGEMENT OF HEART-FAILURE - IMPLICATIONS OF CLINICAL-TRIALS FOR CLINICAL-PRACTICE - PROCEEDINGS OF A SYMPOSIUM SPONSORED BY THE NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE .4. ASSESSMENT OF CLINICAL OUTCOME IN HEART-FAILURE - DISCUSSION-IX SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Discussion C1 UNIV SO CALIF,SCH MED,LOS ANGELES,CA. MCMASTER UNIV,HLTH SCI CTR,HAMILTON,ON,CANADA. US FDA,CTR DRUG EVALUAT & RES,OFF DRUG EVALUAT 1,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. COLUMBIA UNIV COLL PHYS & SURG,DIV CIRCULATORY PHYSIOL,NEW YORK,NY. COLUMBIA UNIV COLL PHYS & SURG,CTR HEART FAILURE RES,NEW YORK,NY. HAMILTON GEN HOSP,HAMILTON,ON,CANADA. RP PITT, B (reprint author), UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,DIV CARDIOL,ANN ARBOR,MI 48109, USA. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1993 VL 22 IS 4 SU A BP A192 EP A193 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MR869 UT WOS:A1993MR86900036 ER PT J AU SUZICH, JA TAMURA, JK PALMERHILL, F WARRENER, P GRAKOUI, A RICE, CM FEINSTONE, SM COLLETT, MS AF SUZICH, JA TAMURA, JK PALMERHILL, F WARRENER, P GRAKOUI, A RICE, CM FEINSTONE, SM COLLETT, MS TI HEPATITIS-C VIRUS NS3 PROTEIN POLYNUCLEOTIDE-STIMULATED NUCLEOSIDE TRIPHOSPHATASE AND COMPARISON WITH THE RELATED PESTIVIRUS AND FLAVIVIRUS ENZYMES SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL DIARRHEA VIRUS; PUTATIVE HELICASES; NON-A; EXPRESSION; REPLICATION; SUPERFAMILY; SEQUENCES; POTYVIRUS; MEMBERS; DISEASE AB Sequence motifs within the nonstructural protein NS3 of members of the Flaviviridae family suggest that this protein possesses nucleoside triphosphatase (NTPase) and RNA helicase activity. The RNA-stimulated NTPase activity of this protein from prototypic members of the Pestivirus and Flavivirus genera has recently been established and enzymologically characterized. Here, we experimentally demonstrate that the NS3 protein from a member of the third genus of Flaviviridae, human hepatitis C virus (HCV), also possesses a polynucleotide-stimulated NTPase activity. Characterization of the purified HCV NTPase activity showed that it exhibited reaction condition optima with respect to pH, MgCl2, and salt identical to those of the representative pestivirus and flavivirus enzymes. However, each NTPase also possessed several unique properties when compared with one another. Notably, the profile of polynucleotide stimulation of the NTPase activity was distinct for the three enzymes. The HCV NTPase was the only one whose activity was significantly enhanced by a deoxyribopolynucleotide. Additional distinguishing features among the three enzymes relating to the kinetic properties of their NTPase activities are discussed. These studies provide a foundation for investigation of the putative RNA helicase activity of these proteins and for further study of the role of the NS3 proteins of members of the Flaviviridae in the replication cycle of these viruses. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BETHESDA,MD 20892. MEDIMMUNE INC,GAITHERSBURG,MD 20878. WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO 63110. FU NCI NIH HHS [CA57973] NR 38 TC 261 Z9 264 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1993 VL 67 IS 10 BP 6152 EP 6158 PG 7 WC Virology SC Virology GA LX120 UT WOS:A1993LX12000051 PM 8396675 ER PT J AU NAKAMURA, GR BYRN, R WILKES, DM FOX, JA HOBBS, MR HASTINGS, R WESSLING, HC NORCROSS, MA FENDLY, BM BERMAN, PW AF NAKAMURA, GR BYRN, R WILKES, DM FOX, JA HOBBS, MR HASTINGS, R WESSLING, HC NORCROSS, MA FENDLY, BM BERMAN, PW TI STRAIN SPECIFICITY AND BINDING-AFFINITY REQUIREMENTS OF NEUTRALIZING MONOCLONAL-ANTIBODIES TO THE C4 DOMAIN OF GP120 FROM HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID AIDS VIRUS; ENVELOPE GLYCOPROTEIN; EXTRACELLULAR DOMAIN; NUCLEOTIDE-SEQUENCE; RECEPTOR-BINDING; CD4 RECEPTOR; HTLV-III; HIV-1; EPITOPE; VARIANTS AB The binding properties of seven CD4-blocking monoclonal antibodies raised against recombinant gp120 of human immunodeficiency virus type 1 strain MN (HIV-1MN) and two CD4-blocking monoclonal antibodies to recombinant envelope glycoproteins gp120 and gp160 of substrain IIIB of HIV(LAI) were analyzed. With a panel of recombinant gp120s from seven diverse HIV-1 isolates, eight of the nine antibodies were found to be strain specific and one was broadly cross-reactive. Epitope mapping revealed that all nine antibodies bound to epitopes located in the fourth conserved domain (C4) of gp120. Within this region, three distinct epitopes could be identified: two were polymorphic between HIV-1 strains, and one was highly conserved. Studies with synthetic peptides demonstrated that the conserved epitope, recognized by antibody 13H8, was located between residues 431 and 439. Site-directed mutagenesis of gp120 demonstrated that residue 429 and/or 432 was critical for the binding of the seven antibodies to gp120 from HIV-1MN. Similarly, residues 423 and 429 were essential for the binding of monoclonal antibody 5C2 raised against gp120 from HIV-1IIIB. The amino acids located at positions 423 and 429 were found to vary between strains of HIV-1 as well as between molecular clones derived from the MN and LAI isolates of HIV-1. Polymorphism at these positions prevented the binding of virus-neutralizing monoclonal antibodies and raised the possibility that HIV-1 neutralization serotypes may be defined on the basis of C4 domain sequences. Analysis of the binding characteristics of the CD4-blocking antibodies demonstrated that their virus-neutralizing activity was directly proportional to their gp120-binding affinity. These studies account for the strain specificity of antibodies to the C4 domain of gp120 and demonstrate for the first time that antibodies to this region can be as effective as those directed to the principal neutralizing determinant (V3 domain) in neutralizing HIV-1 infectivity. C1 GENENTECH INC,DEPT IMMUNOL,S SAN FRANCISCO,CA 94080. GENENTECH INC,DEPT PHARMACOL,S SAN FRANCISCO,CA 94080. US FDA,DIV VIROL,BETHESDA,MD 20892. GENENTECH INC,DEPT HYBRIDOMA DEV,S SAN FRANCISCO,CA 94080. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NEW ENGLAND DEACONESS HOSP,DIV HEMATOL & ONCOL,BOSTON,MA 02215. NR 52 TC 45 Z9 45 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1993 VL 67 IS 10 BP 6179 EP 6191 PG 13 WC Virology SC Virology GA LX120 UT WOS:A1993LX12000054 PM 7690420 ER PT J AU EVANS, FE DECK, J HERRENOSAENZ, D FU, PP AF EVANS, FE DECK, J HERRENOSAENZ, D FU, PP TI NMR-INVISIBLE NUCLEOSIDES IN ADDUCTS FORMED FROM CARCINOGENIC NITROBENZO[A]PYRENES SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE CHEMICAL EXCHANGE; RING-CURRENT FIELD; 2'-DEOXYGUANOSINE; NITROBENZO[A]PYRENE; CARCINOGEN NUCLEOSIDE ADDUCTS; POLYCYCLIC AROMATIC HYDROCARBONS; EXCHANGE SPECTROSCOPY ID NUCLEAR MAGNETIC-RESONANCE; DNA ADDUCTS; PURINE NUCLEOSIDES; CONFORMATION; SPECTROSCOPY; NUCLEOTIDES; C-13; SYN; DEOXYGUANOSINE; MODEL AB Anomalous H-1 NMR spectra have been obtained for two related carcinogen-nucleoside adducts in which a 1- or 3-aminobenzo [a] pyrene ring is bound from its C-6 position to the N-2 position of 2'-deoxyguanosine. NOESY and COSY measurements at low temperature in methanol-d4 revealed chemical exchange between at least two forms. Large chemical shift differences exist between subspectra for all corresponding protons of the nucleoside moiety, whereas all such chemical shift differences are small for the protons of the benzo[a]pyrene moiety. Thus, at intermediate rates of exchange, the nucleoside resonances are broadened beyond recognition, whereas the aminobenzo[a]pyrene resonances appear normal. This is linked with the large anisotropic ring-current field from the carcinogen ring system, and restricted internal rotation at the site of attachment of the carcinogen to the nucleic acid base. The possibility of an absence of resonances from a nucleoside moiety can complicate structure elucidation of unknown carcinogen-nucleoside adducts and related compounds, especially in trace analysis. RP EVANS, FE (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 39 TC 3 Z9 3 U1 0 U2 0 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 OCT PY 1993 VL 31 IS 10 BP 931 EP 936 DI 10.1002/mrc.1260311011 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA MB689 UT WOS:A1993MB68900010 ER PT J AU BARILE, MF GRABOWSKI, MW KAPATAISZOUMBOS, K BROWN, B HU, PC CHANDLER, DKF AF BARILE, MF GRABOWSKI, MW KAPATAISZOUMBOS, K BROWN, B HU, PC CHANDLER, DKF TI EXPERIMENTALLY-INDUCED MYCOPLASMA-PNEUMONIAE PNEUMONIA IN CHIMPANZEES SO MICROBIAL PATHOGENESIS LA English DT Article DE MYCOPLASMA-PNEUMONIAE; CHIMPANZEE; PRIMARY ATYPICAL PNEUMONIA; PATHOGENESIS; IMMUNOLOGICAL RESPONSE ID INFECTION; GENITALIUM; ANTIBODIES; HAMSTERS; PROTEIN C1 PRIMATE RES INST,HOLLOMAN AFB,NM 88330. UNIV N CAROLINA,SCH MED,DEPT PEDIAT,CHAPEL HILL,NC 27514. RP BARILE, MF (reprint author), US FDA,CTR BIOL EVALUAT & RES,MYCOPLASMA LAB,BETHESDA,MD 20892, USA. NR 42 TC 9 Z9 9 U1 0 U2 0 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 OCT PY 1993 VL 15 IS 4 BP 243 EP 253 DI 10.1006/mpat.1993.1075 PG 11 WC Immunology; Microbiology SC Immunology; Microbiology GA MM625 UT WOS:A1993MM62500001 PM 8309353 ER PT J AU HANES, DE CHANDLER, DKF AF HANES, DE CHANDLER, DKF TI THE ROLE OF A 40-MEGADALTON PLASMID IN THE ADHERENCE AND HEMOLYTIC PROPERTIES OF AEROMONAS-HYDROPHILA SO MICROBIAL PATHOGENESIS LA English DT Note DE AEROMONAS-HYDROPHILA; PLASMID; PHENOTYPIC CHANGES; HEMOLYSIS; ANTIBIOTIC RESISTANCE ID DNA C1 US FDA,DIV BIOL INVEST NEW DRUGS,ROCKVILLE,MD 20852. RP HANES, DE (reprint author), US FDA,DIV VIRULENCE ASSESSMENT,HFS-236,200 C ST SW,WASHINGTON,DC 20204, USA. NR 14 TC 10 Z9 11 U1 0 U2 0 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 OCT PY 1993 VL 15 IS 4 BP 313 EP 317 DI 10.1006/mpat.1993.1081 PG 5 WC Immunology; Microbiology SC Immunology; Microbiology GA MM625 UT WOS:A1993MM62500007 PM 8309357 ER PT J AU DEPAOLA, A HILL, WE HARRELL, FM AF DEPAOLA, A HILL, WE HARRELL, FM TI OLIGONUCLEOTIDE PROBE DETERMINATION OF TETRACYCLINE-RESISTANT BACTERIA ISOLATED FROM CATFISH PONDS SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE OLIGONUCLEOTIDE PROBES; TETRACYCLINE-RESISTANT BACTERIA; CATFISH PONDS ID NUCLEOTIDE-SEQUENCE; GENE C1 US FDA,SEAFOOD PROD RES CTR,BOTHELL,WA 98041. US FDA,MIDWEST LAB MICROBIAL INVEST,MINNEAPOLIS,MN 55401. RP DEPAOLA, A (reprint author), US FDA,DIV SEAFOOD RES,DAUPHIN ISL,AL 36528, USA. NR 10 TC 14 Z9 15 U1 1 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD OCT PY 1993 VL 7 IS 5 BP 345 EP 348 DI 10.1006/mcpr.1993.1051 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA MG334 UT WOS:A1993MG33400002 PM 8264667 ER PT J AU GARCIA, PA BREDESEN, DE VINTERS, HV VONEINSIEDEL, RG WILLIAMS, RL KAHN, JO BYERS, VS LEVIN, AS WAITES, LA MESSING, RO AF GARCIA, PA BREDESEN, DE VINTERS, HV VONEINSIEDEL, RG WILLIAMS, RL KAHN, JO BYERS, VS LEVIN, AS WAITES, LA MESSING, RO TI NEUROLOGICAL REACTIONS IN HIV-INFECTED PATIENTS TREATED WITH TRICHOSANTHIN SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE TRICHOSANTHIN; GLQ223(R); RIBOSOME-INACTIVATING PROTEINS; PROGRESSIVE DIFFUSE LEUKOENCEPHALOPATHY; ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS); HUMAN IMMUNODEFICIENCY VIRUS (HIV) ID AIDS; BRAINS; GLQ223 AB Trichosanthin is a ribosome-inactivating protein that is being studied as a possible treatment for patients infected with human immunodeficiency virus (HIV). We report the clinical and pathological features in two patients who experienced neurological reactions to trichosanthin. Both patients were neurologically asymptomatic prior to treatment but developed coma and multifocal neurological deficits after treatment. Neuropathological examination revealed regions of severe, multifocal necrosis with histio-cytic infiltrates. These reactions to trichosanthin may be mediated by soluble factors released by HIV-infected macrophages. C1 UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PATHOL,LOS ANGELES,CA 90024. GENELABS INC,REDWOOD CITY,CA. US FDA,OFF GENER DRUGS,ROCKVILLE,MD 20857. SAN FRANCISCO GEN HOSP,DEPT MED,SAN FRANCISCO,CA 94110. IMMUNOL INC,SAN FRANCISCO,CA. UNIV NOTTINGHAM,NOTTINGHAM NG7 2RD,ENGLAND. RP GARCIA, PA (reprint author), UNIV CALIF SAN FRANCISCO,DEPT NEUROL M-794,SAN FRANCISCO,CA 94143, USA. RI Messing, Robert/D-3642-2015 OI Messing, Robert/0000-0002-5345-4431 NR 9 TC 18 Z9 19 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD OCT PY 1993 VL 19 IS 5 BP 402 EP 405 DI 10.1111/j.1365-2990.1993.tb00461.x PG 4 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA MB063 UT WOS:A1993MB06300005 PM 8278023 ER PT J AU HILL, JC FLANNERY, GM FRASER, BA AF HILL, JC FLANNERY, GM FRASER, BA TI IDENTIFICATION OF ALPHA-CARBOXAMIDATED AND CARBOXY-TERMINAL GLYCINE FORMS OF PEPTIDES IN BOVINE HYPOTHALAMUS, BOVINE PITUITARY AND PORCINE HEART EXTRACTS SO NEUROPEPTIDES LA English DT Article ID AMIDATING MONOOXYGENASE ACTIVITY; CONVERSION; PROTEINS; AMIDE; POLYPEPTIDE; MECHANISM; HORMONES; AMINES; BRAIN AB Two chemical assays have been developed for identifying and quantifying peptides which either could be biologically active by virtue of their alpha-carboxamidation or could be substrates for peptidylglycine alpha-amidating mono-oxygenase. The first assay is specific for the alpha-carboxamide of peptides. Using bis[trifluoroacetoxy]iodobenzene, the alpha-carboxamide was converted via a Hoffman reaction into a primary amine, which was then quantified by ninhydrin. The second assay is specific for glycine at the carboxy-terminus of a peptide. Glycine at the carboxy-terminus was derivatized to form 2-thiohydantoin, which was then separated and quantified by reverse phase HPLC. These assays were used to detect peptides in HPLC-separated extracts of bovine hypothalamus, bovine anterior lobe pituitary and porcine heart which may be of biological interest. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 26 TC 3 Z9 3 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD OCT PY 1993 VL 25 IS 4 BP 255 EP 264 DI 10.1016/0143-4179(93)90110-V PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA MB069 UT WOS:A1993MB06900005 PM 8255401 ER PT J AU JACKSON, GJ AF JACKSON, GJ TI THOUGHTS ON THE ENTRAPMENT OF NEMATODES BY FUNGI SO PARASITOLOGY TODAY LA English DT Letter RP JACKSON, GJ (reprint author), US FDA,WASHINGTON,DC 20204, USA. NR 5 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD OCT PY 1993 VL 9 IS 10 BP 352 EP 352 DI 10.1016/0169-4758(93)90081-P PG 1 WC Parasitology SC Parasitology GA LX693 UT WOS:A1993LX69300006 PM 15463666 ER PT J AU ROBBINS, JB PITTMAN, M TROLLFORS, B LAGERGARD, TA TARANGER, J SCHNEERSON, R AF ROBBINS, JB PITTMAN, M TROLLFORS, B LAGERGARD, TA TARANGER, J SCHNEERSON, R TI PRIMUM-NON-NOCERE - A PHARMACOLOGICALLY INERT PERTUSSIS TOXOID ALONE SHOULD BE THE NEXT PERTUSSIS-VACCINE SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Review DE PERTUSSIS; PERTUSSIS TOXOID; VACCINE ID LYMPHOCYTOSIS-PROMOTING FACTOR; ISLET-ACTIVATING PROTEIN; OUTER-MEMBRANE PROTEIN; BORDETELLA ADENYLATE-CYCLASE; COMPONENT DTP VACCINE; HAMSTER OVARY CELLS; INFLUENZAE TYPE-B; WHOLE-CELL; WHOOPING-COUGH; FILAMENTOUS HEMAGGLUTININ C1 GOTHENBURG UNIV,DEPT PEDIAT,S-41124 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT MICROBIOL & IMMUNOL,S-41124 GOTHENBURG,SWEDEN. US FDA,CTR BIOL RES & REVIEW,BETHESDA,MD 20014. RP ROBBINS, JB (reprint author), NICHHD,LAB & DEV & MOLEC IMMUN,BLDG 6,ROOM 145,BETHESDA,MD 20892, USA. NR 239 TC 39 Z9 39 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 OCT PY 1993 VL 12 IS 10 BP 795 EP 807 DI 10.1097/00006454-199310000-00001 PG 13 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA MB703 UT WOS:A1993MB70300001 PM 8284114 ER PT J AU REEPMEYER, JC ZIELINSKI, WL LEAKEY, JEA SI, Y AF REEPMEYER, JC ZIELINSKI, WL LEAKEY, JEA SI, Y TI SYNTHESIS AND STABILITY OF ISOTOPICALLY LABELED P-CHLORO-M-XYLENOL (PCMX) SO PHARMACEUTICAL RESEARCH LA English DT Article DE P-CHLORO-M-XYLENOL; 4-CHLORO-3,5-DIMETHYLPHENOL (PCMX); RADIOLABEL SYNTHESIS; ISOTOPES; STABILITY; REACTION KINETICS; IN-VITRO STUDIES ID META-XYLENOL; CHLOROXYLENOL AB The synthesis, reaction kinetics, and pH stability of isotopically labeled p-chloro-m-xylenol (PCMX) were evaluated. While base catalysis was more rapid than acid catalysis, the latter allowed the use of a cosolvent for deuterium and tritium labeling using as little as 250 muL labeled water. Both acid and base catalysis were markedly more rapid than that reported previously for the deuteration of PCMX and related phenols. Isotopic labeling occurred only at the 2 and 6 ring positions, ortho to the phenolic group of PCMX. No deuterium loss was observed after storage for 21 days at 37-degrees-C over a pH range of 2-14. Isotopic loss was observed only below pH 2. The prepared H-3-labeled PCMX had a specific activity of 1.18 mCi/mmol, a radiochemical purity of 99.0%, and a chemical purity exceeding 99.0%, with a high stability during prolonged cold storage. C1 US FDA,CTR DRUG EVALUAT & RES,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 12 TC 0 Z9 0 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 OCT PY 1993 VL 10 IS 10 BP 1466 EP 1470 DI 10.1023/A:1018975309429 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA MA421 UT WOS:A1993MA42100012 PM 8272409 ER PT J AU WEIR, JP ELKINS, KL AF WEIR, JP ELKINS, KL TI REPLICATION-INCOMPETENT HERPESVIRUS VECTOR DELIVERY OF AN INTERFERON-ALPHA GENE INHIBITS HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION IN HUMAN MONOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLYCOPROTEIN-C GENE; SIMPLEX VIRUS; TYPE-1; INFECTION; IDENTIFICATION; LYMPHOCYTES; EXPRESSION; SEQUENCES; THERAPY; REGION AB Human monocytes and macrophages are nondividing cells that serve as a major reservoir for human immunodeficiency virus (HIV) at all stages of infection. To investigate viral-mediated gene delivery as a means of inhibiting HIV replication in human monocytes, a replication-incompetent herpes simplex virus vector was developed that expressed human interferon alpha. Monocytes infected with this herpes simplex virus vector and then challenged with HIV showed dramatically reduced cytopathic effects and HIV replication compared to control treated monocytes. Similar effects on HIV replication were observed if monocytes were first infected with HIV and then treated with the recombinant vectors. These results demonstrate that replication-incompetent herpes simplex virus gene delivery of interferon alpha directly to human monocytes can greatly decrease HIV replication and suggest that such a vector might deliver therapeutically important genes directly to sites of HIV infection. C1 WALTER REED ARMY INST RES,DEPT CELLULAR IMMUNOL,WASHINGTON,DC 20307. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 25 TC 16 Z9 16 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 1 PY 1993 VL 90 IS 19 BP 9140 EP 9144 DI 10.1073/pnas.90.19.9140 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MA595 UT WOS:A1993MA59500080 PM 8415668 ER PT J AU CHEN, J AF CHEN, J TI A MALFORMATION INCIDENCE DOSE-RESPONSE MODEL INCORPORATING FETAL WEIGHT AND OR LITTER SIZE AS COVARIATES SO RISK ANALYSIS LA English DT Article DE CONDITIONAL GAUSSIAN REGRESSION CHAIN MODEL; GENERALIZED ESTIMATING EQUATIONS; MIXED EFFECT MODEL ID LONGITUDINAL DATA AB A dose-response model is often fit to bioassay data to provide a mathematical relationship between the incidence of a developmental malformation and dose of a toxicant. To utilize the interrelations among the fetal weight, incidence of malformation and number of the live fetuses, a conditional Gaussian regression chain model is proposed to model the dose-response function for developmental malformation incidence using the litter size and/or the fetal weight as covariates. The litter size is modeled as a function of dose, the fetal weight is modeled as a function of dose conditional on the litter size, and the malformation incidence is modeled as a function of dose conditional on both the litter size and the fetal weight, which itself is also conditional on the litter size. Data from a developmental experiment conducted at the National Center for Toxicological Research to investigate the growth stunting and increased incidence of cleft palate induced by Dexamethasone (DEX) exposure in rats was used as an illustration. RP CHEN, J (reprint author), NATL CTR TOXICOL RES,DIV BIOMETRY & RISK ASSESSMENT,HFT-20,JEFFERSON,AR 72079, USA. FU FDA HHS [FDA 224-89-0008] NR 12 TC 20 Z9 20 U1 0 U2 1 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 OCT PY 1993 VL 13 IS 5 BP 559 EP 564 DI 10.1111/j.1539-6924.1993.tb00015.x PG 6 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA MH191 UT WOS:A1993MH19100014 PM 8259446 ER PT J AU JIN, Y GIRI, C KLUTCH, MJ SHEPP, D WRIGHT, SE AF JIN, Y GIRI, C KLUTCH, MJ SHEPP, D WRIGHT, SE TI IMPROVED IMMUNOGENICITY OF RECOMBINANT VACCINIA VIRUS-ANCHORED GP120 LACKING GP41 SO VACCINE LA English DT Note DE IMMUNOGENICITY; FUSION PROTEIN ID ENVELOPE GLYCOPROTEIN; CELL-SURFACE; IMMUNODEFICIENCY; TRANSPORT; CLEAVAGE AB To produce a vaccine against human immunodeficiency virus-1 with improved immunogenicity, the transmembrane and cytoplasmic tail regions of human immunodeficiency virus-1 were replaced with those of the Vesicular Stomatitis Virus glycoprotein, and cloned into vaccinia virus. This recombinant vaccinia virus, vvE13, was compared to one expressing full length envelope gp160, vvE1. Env products of both were located on the cell surface. Antibody response, lymphocyte proliferation and cytotoxicity were better with vvE13 than with vvE1 inoculated mice. C1 VAMC 111,6010 AMARILLO BLVD W,AMARILLO,TX 79106. TEXAS TECH UNIV,HLTH SCI CTR,DEPT INTERNAL MED,LUBBOCK,TX 79430. DHHS,FDA,CBD,OBRR,DIV VIROL,BETHESDA,MD. TEXAS TECH UNIV,HLTH SCI CTR,DEPT BIOCHEM & MOLEC BIOL,LUBBOCK,TX 79430. NR 18 TC 7 Z9 7 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD OCT PY 1993 VL 11 IS 13 BP 1280 EP 1282 DI 10.1016/0264-410X(93)90095-F PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MC984 UT WOS:A1993MC98400002 PM 8296479 ER PT J AU LI, BG CLARK, HF GOUVEA, V AF LI, BG CLARK, HF GOUVEA, V TI NUCLEOTIDE-SEQUENCE OF THE VP4-ENCODING GENE OF AN UNUSUAL HUMAN ROTAVIRUS (HCR3) SO VIROLOGY LA English DT Note ID AMINO-ACID-SEQUENCE; POLYMERASE CHAIN-REACTION; NEUTRALIZATION EPITOPES; UNIQUE VP4; IDENTIFICATION; STRAINS; SPECIFICITIES; UK C1 CHILDRENS HOSP PHILADELPHIA,DIV INFECT DIS,PHILADELPHIA,PA 19104. RP LI, BG (reprint author), US FDA,DIV MOLEC BIOL RES & EVALUAT,MOLEC BIOL BRANCH,WASHINGTON,DC 20204, USA. NR 28 TC 51 Z9 51 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 0042-6822 J9 VIROLOGY JI Virology PD OCT PY 1993 VL 196 IS 2 BP 825 EP 830 DI 10.1006/viro.1993.1540 PG 6 WC Virology SC Virology GA LY071 UT WOS:A1993LY07100047 PM 8396809 ER PT J AU BROWN, RL BERT, RJ EVANS, FE KARPEN, JW AF BROWN, RL BERT, RJ EVANS, FE KARPEN, JW TI ACTIVATION OF RETINAL ROD CGMP-GATED CHANNELS - WHAT MAKES FOR AN EFFECTIVE 8-SUBSTITUTED DERIVATIVE OF CGMP SO BIOCHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; CYCLIC-GMP; SENSITIVE CONDUCTANCE; OUTER SEGMENTS; ION CHANNEL; CELLS; MEMBRANES; ANALOGS AB Analogs of cGMP bearing diverse substituents at the C-8 position of the guanine ring system have been shown to activate the cGMP-activated channel of retinal rods at concentrations lower than cGMP itself. In an effort to understand this behavior, we synthesized eight novel C-8-substituted derivatives and tested their ability to activate channels in excised patches from salamander rod outer segments. We express the effectiveness of each analog as a ratio (in brackets) of the concentration required to open half of the channels in a patch to that required of 8-Br-cGMP, previously shown to be about 10 times more effective than cGMP. Five of the derivatives contained a thio substitution at C-8: n-propylthio-cGMP [0.61], sulfoethylthio-cGMP [0.90], carboxyethylthio-cGMP [0.97], aminoethylthio-cGMP [2.8], and (trimethylamino)ethylthio-cGMP [8.5]. Three of the derivatives contained an amino substitution at C-8: carboxyethylamino-cGMP [22], n-propylamino-cGMP [25], and aminoethylamino-cGMP [230]. The results indicate that thio-substitution at C-8 produces more effective analogs than does amino-substitution, regardless of the chemical nature of the terminal functional group. Derivatives containing neutral and apolar tails opened channels at much lower concentrations than their positively-charged counterparts with the same C-8 substituent. Analogs having negatively-charged tails were also more effective than those with positive charge but not quite as effective as those with neutral tails. H-1 NMR measurements of the H2' chemical shift, previously shown to be sensitive to conformation about the N-glycosidic bond, revealed no significant differences in the syn-anti equilibrium between pairs of amino- or thio-substituted derivatives that opened channels at widely differing concentrations. The disparities in analog effectiveness most likely reflect differences in the chemical interactions between the C-8-substitutions or neighboring atoms affected by the substitutions and the channel's binding sites. C1 UNIV COLORADO,SCH MED,DEPT PHYSIOL,DENVER,CO 80262. US FDA,NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. FU NEI NIH HHS [EY06425, EY09275]; NINDS NIH HHS [T32NS07083] NR 31 TC 26 Z9 26 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 28 PY 1993 VL 32 IS 38 BP 10089 EP 10095 DI 10.1021/bi00089a026 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LZ638 UT WOS:A1993LZ63800026 PM 7691169 ER PT J AU STROM, BL CARSON, JL SCHINNAR, R SNYDER, ES SHAW, M LUNDIN, FE AF STROM, BL CARSON, JL SCHINNAR, R SNYDER, ES SHAW, M LUNDIN, FE TI NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND NEUTROPENIA SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INDUCED BLOOD DYSCRASIAS; INDUCED AGRANULOCYTOSIS; PHENYLBUTAZONE AB Background: The association between nonsteroidal anti-inflammatory drugs (NSAIDs) and neutropenia is based primarily on case reports only. Methods: A population-based, case control study was performed with Medicaid claims data from six states. Cases were defined as patients hospitalized with neutropenia. Four controls per case were randomly chosen, matched for age, sex, state, and year. The frequency of exposure to NSAIDs in the 30 days before hospital admission in the cases was compared with the frequency in the identical period in the controls. The diagnosis of neutropenia was validated by review of medical records. Results: The crude odds ratio for NSAIDs as a class was 3.3 (90% confidence interval, 1.6 to 6.6). The multivariate adjusted odds ratio was 4.2 (90% confidence interval, 2.0 to 8.7). No single class of NSAIDs, nor any individual NSAID, was associated with a unique risk, although the data on individual NSAIDs were sparse. Even excluding phenylbutazone and indomethacin, an increased risk was observed (3.5 [1.6 to 7.6]). Conclusions: Neutropenia is associated with the use of NSAIDs. However, given the low incidence of this disease, the additional number of cases of neutropenia caused by the use of NSAIDs is small. These data do not support the existence of a risk restricted to selected NSAIDs only. C1 UNIV PENN,SCH MED,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104. UMDNJ,ROBERT WOOD JOHNSON MED SCH,DEPT MED,DIV GEN INTERNAL MED,NEW BRUNSWICK,NJ. HLTH INFORMAT DESIGNS INC,DEPT POSTMARKETING SURVEILLANCE,ARLINGTON,VA. US FDA,CTR DRUG EVALUAT & RES,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857. RP STROM, BL (reprint author), UNIV PENN,SCH MED,CTR CLIN EPIDEMIOL & BIOSTAT,PHILADELPHIA,PA 19104, USA. FU FDA HHS [FD-U-000079] NR 29 TC 26 Z9 28 U1 0 U2 0 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 SEP 27 PY 1993 VL 153 IS 18 BP 2119 EP 2124 DI 10.1001/archinte.153.18.2119 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA LY471 UT WOS:A1993LY47100005 PM 8379803 ER PT J AU NICHOLLS, PJ JOHNSON, VG BLANFORD, MD ANDREW, SM AF NICHOLLS, PJ JOHNSON, VG BLANFORD, MD ANDREW, SM TI AN IMPROVED METHOD FOR GENERATING SINGLE-CHAIN ANTIBODIES FROM HYBRIDOMAS SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE SINGLE-CHAIN ANTIBODY; VARIABLE REGION; ANTIBODY FRAGMENT; CLONING; HYBRIDOMA; IN-VITRO EXPRESSION ID IMMUNOGLOBULIN VARIABLE DOMAINS; ESCHERICHIA-COLI; ANTIGEN-BINDING; PSEUDOMONAS EXOTOXIN; DIPHTHERIA-TOXIN; REGION GENES; CLONING; FV; RECEPTOR; CONSTRUCTION AB Cloning the correct V(L) kappa gene from hybridomas derived from MOPC-21 can be problematic because such cell lines variably express a transcript which is aberrantly rearranged at the VJ recombination site. Cellular levels of the aberrant transcript can exceed that of productive light chain RNA, so a large proportion of the V(L) gene-derived products obtained on PCR amplification of hybridoma cDNA may not encode a functional protein. We have developed a method in which antibody variable region genes are recovered from hybridoma cDNA using a unique set of V gene family-specific primers; the V region genes are then spliced by PCR, in the form 5'-V(L)-LINKER-V(H)-3' (where the linker encodes [GlyGlyGlyGlySer]3), and cloned into an expression vector under control of T7 RNA polymerase. Plasmid DNA is isolated from colonies, and the insert is expressed in an in vitro rabbit reticulocyte lysate-based coupled transcription/translation system, in a microtiter plate format. Since aberrantly rearranged V(L) kappa genes contain a translation termination codon at amino acid position 105, only constructs containing the correctly rearranged gene produce a protein of the predicted size. We demonstrate the method by producing the single-chain form of OKT9, a murine IgG1 which binds to the human transferrin receptor, and extend the results to show thal the protein generated by the in vitro expression system retains the antigen binding properties of the parent antibody. Our method will be generally useful for screening single-chain antibodies for function prior to large scale production in vivo. C1 NINCDS, SURG NEUROL BRANCH, BIOCHEM SECT, BETHESDA, MD 20892 USA. FDA, CBER, DIV BACTERIAL PROD, BACTERIAL TOXINS LAB, BETHESDA, MD 20892 USA. NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. NR 28 TC 41 Z9 42 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 EI 1872-7905 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP 27 PY 1993 VL 165 IS 1 BP 81 EP 91 DI 10.1016/0022-1759(93)90109-K PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA MB511 UT WOS:A1993MB51100010 PM 8409471 ER PT J AU LARNER, AC DAVID, M FELDMAN, GM IGARASHI, K HACKETT, RH WEBB, DSA SWEITZER, SM PETRICOIN, EF FINBLOOM, DS AF LARNER, AC DAVID, M FELDMAN, GM IGARASHI, K HACKETT, RH WEBB, DSA SWEITZER, SM PETRICOIN, EF FINBLOOM, DS TI TYROSINE PHOSPHORYLATION OF DNA-BINDING PROTEINS BY MULTIPLE CYTOKINES SO SCIENCE LA English DT Article ID INTERFERON-ALPHA; TRANSCRIPTION FACTOR; SIGNAL TRANSDUCTION; GENE; ACTIVATOR; ISGF-3; GAMMA AB Interferon-alpha (IFN-alpha) and IFN-gamma regulate gene expression by tyrosine phosphorylation of several transcription factors that have the 91-kilodalton (p91) protein of interferon-stimulated gene factor-3 (ISGF-3) as a common component. Interferon-activated protein complexes bind enhancers present in the promoters of early response genes such as the high-affinity Fcgamma receptor gene (FcgammaRI). Treatment of human peripheral blood monocytes or basophils with interleukin-3 (IL-3), IL-5, IL-10, or granulocyte-macrophage colony-stimulating factor (GM-CSF) activated DNA binding proteins that recognized the IFN-gamma response region (GRR) located in the promoter of the FcgammaRI gene. Although tyrosine phosphorylation was required for the assembly of each of these GRR binding complexes, only those formed as a result of treatment with IFN-gamma or IL-10 contained p91. Instead, complexes activated by IL-3 or GM-CSF contained a tyrosine-phosphorylated protein of 80 kilodaltons. Induction of FcgammaRI RNA occurred only with IFN-gamma and IL-10, whereas pretreatment of cells with GM-CSF or IL-3 inhibited IFN-gamma induction of FcgammaRI RNA. Thus, several cytokines other than interferons can activate putative transcription factors by tyrosine phosphorylation. RP LARNER, AC (reprint author), CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892, USA. NR 14 TC 350 Z9 351 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 24 PY 1993 VL 261 IS 5129 BP 1730 EP 1733 DI 10.1126/science.8378773 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LY584 UT WOS:A1993LY58400025 PM 8378773 ER PT J AU RHEINSTEIN, PH AF RHEINSTEIN, PH TI MEDWATCH - THE FDA MEDICAL PRODUCTS REPORTING PROGRAM SO AMERICAN FAMILY PHYSICIAN LA English DT Article RP RHEINSTEIN, PH (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD SEP 15 PY 1993 VL 48 IS 4 BP 636 EP 638 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA LZ655 UT WOS:A1993LZ65500014 PM 8379493 ER PT J AU VOSTAL, JG SHULMAN, NR AF VOSTAL, JG SHULMAN, NR TI VINCULIN IS A MAJOR PLATELET PROTEIN THAT UNDERGOES CA2+-DEPENDENT TYROSINE PHOSPHORYLATION SO BIOCHEMICAL JOURNAL LA English DT Article ID GLYCOPROTEIN-IIB; RABBIT PLATELETS; KINASE; THROMBIN; TALIN; CELLS; IIIA AB When intracellular Ca2+ pools are released during platelet stimulation by thrombin, elevation of platelet cytosolic Ca2+ concentration induces tyrosine phosphorylation of a 130 kDa protein, and refilling the pools mediates dephosphorylation of this protein [Vostal, Jackson and Shulman (1991) J. Biol. Chem. 266, 16911-16916]. In the present work the 130 kDa protein was identified as vinculin by the following criteria. (1) It is detected on protein immunoblots of thrombin-activated platelets by both monoclonal anti-phosphotyrosine and anti-vinculin antibodies. (2) Removal of N-linked sugars with peptide-N-glycosidase or reduction did not change the molecular mass of vinculin or of the 130 kDa protein on SDS/PAGE. (3) The 130 kDa tyrosine-phosphorylated protein associates with Triton-soluble fraction of platelets as does vinculin. (4) The 130 kDa protein immunoprecipitated by anti-vinculin monoclonal antibody reacts with anti-phosphotyrosine antibody; when immunoprecipitated by anti-phosphotyrosine antibody it reacts with anti-vinculin antibody. (5) The 130 kDa tyrosine-phosphorylated protein and vinculin focus isoelectrically at pI 5.4-5.8. Our finding that vinculin is a major platelet protein that undergoes Ca2+-dependent tyrosine phosphorylation during platelet activation may provide clues to the function of this protein. C1 NIDDKD,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. RP VOSTAL, JG (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20892, USA. NR 28 TC 37 Z9 37 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 SEP 15 PY 1993 VL 294 BP 675 EP 680 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LY645 UT WOS:A1993LY64500010 PM 7691054 ER PT J AU HOUGHTON, JA MORTON, CL ADKINS, DA RAHMAN, A AF HOUGHTON, JA MORTON, CL ADKINS, DA RAHMAN, A TI LOCUS OF THE INTERACTION AMONG 5-FLUOROURACIL, LEUCOVORIN, AND INTERFERON-ALPHA-2A IN COLON-CARCINOMA CELLS SO CANCER RESEARCH LA English DT Article ID ADVANCED COLORECTAL-CARCINOMA; ACID STRAND BREAKS; THYMIDYLATE SYNTHASE; THYMINELESS DEATH; GAMMA-INTERFERON; DNA-POLYMERASES; CYTO-TOXICITY; FOLINIC ACID; FLUOROURACIL; INHIBITION AB Prior studies from these laboratories demonstrated 3.2-fold potentiation of 5-fluorouracil (FUra) cytotoxicity by recombinant human interferon-alpha2a (rIFN-alpha2a) in GC3/cl colon adenocarcinoma cells that was significantly enhanced to 14-fold when FUra was combined with rIFN-alpha2a + a mixture of the diasteroisomers of the biologically active (6S) and inactive (6R) leucovorin or 5-formyl-H4PteGlu (LV), events that were reversible by thymidine (dThd). In GC3/clTS-c3/c3 cells, deficient in thymidylate synthase, rIFN-alpha2a cytotoxicity was not influenced by the concentration of dThd, indicating no direct effect at the level of dThd-less stress. Direct assays of thymidylate synthase indicated no significant difference between FUra-induced accumulation of total thymidylate synthase or free or unbound thymidylate synthase in cells receiving FUra + modulators. In addition, the cytotoxic activity of CB3717, a specific quinazoline-based inhibitor of thymidylate synthase, was not potentiated by rIFN-alpha2a. These studies suggested that thymidylate synthase was not the primary target site for rIFN-alpha2a activity. Since data indicated that a 5-fluoropyrimidine was required in the interaction among FUra, LV, and rIFN-alpha2a, attention was focused at the level of DNA. Both DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) induced by FUra were significantly elevated by rIFN-alpha2a and LV administered as single modulators and were influenced by the concentrations of both FUra and rIFN-alpha2a. However, when FUra was combined with LV, rIFN-alpha2a further potentiated the frequency of DNA SSBs, and data correlated with the relative cytotoxic activity of FUra-LV-rIFN-alpha2a combinations. No effect on CB3717-induced DNA SSBs or DSBs by rIFN-alpha2a was demonstrated. Drug exposure for 48 h was required to detect measurable differences in DNA SSB frequency among FUra-LV-rIFN-alpha2a treatment groups and correlated with decreased clonogenic survival under these conditions. Continuous exposure to FUra (72 h) allowed shorter exposures to LV and/or rIFN-alpha2a (48 h) to maintain maximal cytotoxicity. Shorter exposure times for FUra during continuous exposure to the modulators were less cytotoxic. Data suggest that the primary locus of the interaction among FUra, LV, and rIFN-alpha2a lies at the level of DNA. rIFN-alpha2a may exert its effects via enhancement of FUra base excision or incorporation into DNA, events that subsequently become influenced by thymidylate synthase inhibition and dThd-less stress and are further potentiated by LV. Further studies will define the exact target of rIFN-alpha2a action. C1 US FDA, DIV BIOPHARMACEUT, ROCKVILLE, MD 20857 USA. RP HOUGHTON, JA (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT MOLEC PHARMACOL, 332 N LAUDERDALE, MEMPHIS, TN 38101 USA. FU NCI NIH HHS [CA23099, CA32613, CA21765] NR 46 TC 70 Z9 70 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1993 VL 53 IS 18 BP 4243 EP 4250 PG 8 WC Oncology SC Oncology GA LW553 UT WOS:A1993LW55300022 PM 8364921 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI FDA GUIDELINE ON WOMEN IN CLINICAL-TRIALS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 1 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 15 PY 1993 VL 270 IS 11 BP 1290 EP 1290 DI 10.1001/jama.270.11.1290 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LW345 UT WOS:A1993LW34500006 PM 8360956 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI LEVOMETHADYL APPROVED FOR THE TREATMENT OF OPIATE DEPENDENCE 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 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 15 PY 1993 VL 270 IS 11 BP 1290 EP 1290 DI 10.1001/jama.270.11.1290 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LW345 UT WOS:A1993LW34500007 PM 8360956 ER PT J AU HOROWITZ, RS DART, RC GOMEZ, H MOORE, LL FULTON, B FELDHAUS, K BRENT, J STERMITZ, FR BECK, JJ ALESSI, JR WALSENBURG, DO DESMET, PAGM AF HOROWITZ, RS DART, RC GOMEZ, H MOORE, LL FULTON, B FELDHAUS, K BRENT, J STERMITZ, FR BECK, JJ ALESSI, JR WALSENBURG, DO DESMET, PAGM TI JIN BU HUAN TOXICITY IN CHILDREN - COLORADO, 1993 (REPRINTED FROM MMWR, VOL 42, PG 633-636, 1993) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 CTR DIS CONTROL,NATL CTR ENVIRONM HLTH,DIV ENVIRONM HAZARDS & HLTH EFFECTS,ATLANTA,GA 30333. US FDA,CTR FOOD SAFETY & APPL NUTR,BETHESDA,MD 20014. DENVER GEN HOSP,DEPT EMERGENCY,DENVER,CO 80204. COLORADO STATE UNIV,DEPT CHEM,FT COLLINS,CO 80523. COLORADO STATE UNIV,AGR EXPT STN,FT COLLINS,CO 80523. RP HOROWITZ, RS (reprint author), ROCKY MT POISON CTR,DENVER,CO, USA. NR 11 TC 3 Z9 3 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 15 PY 1993 VL 270 IS 11 BP 1298 EP & PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA LW345 UT WOS:A1993LW34500010 ER PT J AU PECK, CC TEMPLE, RJ COLLINS, JM AF PECK, CC TEMPLE, RJ COLLINS, JM TI DRUG-INTERACTIONS - THE DEATH PEN - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP PECK, CC (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 15 PY 1993 VL 270 IS 11 BP 1317 EP 1317 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LW345 UT WOS:A1993LW34500018 ER PT J AU HUMMELL, DS DOOLEY, JS KHAN, AS LAWTON, AR AF HUMMELL, DS DOOLEY, JS KHAN, AS LAWTON, AR TI COORDINATE TRANSCRIPTIONAL CONTROL OF MURINE ENDOGENOUS RETROVIRUS AND IG GENES DURING B-CELL DIFFERENTIATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAVY-CHAIN ENHANCER; LONG TERMINAL REPEATS; IMMUNOGLOBULIN HEAVY; ANTI-MU; PROTEIN-BINDING; MESSENGER-RNA; LIPOPOLYSACCHARIDE; SUPPRESSION; PROMOTER; VIRUS AB Proliferation and differentiation of B lymphocytes are usually concurrent but independently regulated events. Anti-mu treatment of murine B lymphocytes stimulated with LPS provides a model system in which proliferation and differentiation may be independently studied. This treatment causes enhanced proliferation but with coordinate suppression of transcription of a family of unrelated genes including those for Ig heavy and light chains, J chain, and endogenous murine leukemia virus (MuLV) sequences. We show that in comparison to B lymphocytes stimulated with LPS alone cells stimulated with a combination of anti-mu and LPS exhibit relatively increased amounts of a nuclear binding factor(s), NFmuE1, which interacts with the B (muE1) site of the IgH enhancer; binding is strongly inhibited by a synthetic probe of the B sequence. A negative regulatory sequence contained within the upstream conserved region (UCR) of the MuLV long terminal repeat (LTR) is identical to the complement of muE1 in eight of nine bases and inhibits binding of NFmuE1 to the IgH enhancer probe. The muE1 site is also present 3' to the kappa-light chain gene; binding of this sequence to a repressor protein may coordinately suppress the transcription of mu, kappa, and MuLV genes. Others have reported that the cDNA encoding NFmuE1, also known as muEBP-B, CF-1, and YY-1, predicts a protein with structural features consistent with variable function as either a transcriptional activator or repressor. C1 VANDERBILT UNIV,DEPT MICROBIOL & IMMUNOL,NASHVILLE,TN 37232. US FDA,DIV VIROL,RETROVIRAL RES LAB,BETHESDA,MD 20892. RP HUMMELL, DS (reprint author), VANDERBILT UNIV,DEPT PEDIAT,DIV PEDIAT IMMUNOL,MCN D-3237,NASHVILLE,TN 37232, USA. FU NIAID NIH HHS [AI-23766] NR 39 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1993 VL 151 IS 6 BP 3131 EP 3139 PG 9 WC Immunology SC Immunology GA LY492 UT WOS:A1993LY49200022 PM 8397253 ER PT J AU MADDEN, JM AF MADDEN, JM TI FISH AS A THREAT TO HUMAN HEALTH DUE TO THE PRESENCE OF AEROMONAS-HYDROPHILA SO MEDICAL MICROBIOLOGY LETTERS LA English DT Article; Proceedings Paper CT 4TH INTERNATIONAL SYMP ON AEROMONAS AND PLESIOMONAS CY MAY 00-16, 1993 CL ATLANTA, GA RP MADDEN, JM (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 1018-4627 J9 MED MICROBIOL LETT JI Med. Microbiol. Lett. PD SEP 15 PY 1993 VL 2 IS 6 BP 335 EP 338 PG 4 WC Microbiology SC Microbiology GA LY068 UT WOS:A1993LY06800007 ER PT J AU JOHNSON, GR PRIGENT, SA GULLICK, WJ STROMBERG, K AF JOHNSON, GR PRIGENT, SA GULLICK, WJ STROMBERG, K TI CHARACTERIZATION OF HIGH AND LOW-MOLECULAR-WEIGHT FORMS OF AMPHIREGULIN THAT DIFFER IN GLYCOSYLATION AND PEPTIDE CORE LENGTH - EVIDENCE THAT THE NH2-TERMINAL REGION IS NOT CRITICAL FOR BIOACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ASPARAGINE-LINKED OLIGOSACCHARIDES; N-GLYCOSIDASE-F; FIBROBLAST GROWTH; CELL-SURFACE; FACTOR-ALPHA; EXTRACELLULAR-MATRIX; COLORECTAL TUMORS; OVARIAN-CARCINOMA; EPITHELIAL-CELLS AB Human amphiregulin (AR) is a polypeptide growth regulator which acts by binding to and activating the epidermal growth factor (EGF) receptor tyrosine kinase. AR consists of an EGF-like domain and an NH2-terminal extension which contains potential glycosylation sites and nuclear localization signals. Two high molecular weight species which had molecular masses of approximately 16.5 kDa (HMW-AR1 and HMW-AR2) and a approximately 9.5-kDa low molecular weight form (LMW-AR) were isolated from the conditioned medium of phorbol 12-myristate 13-acetate-treated MCF-7 human breast carcinoma cells by sequential heparin affinity, immunoaffinity, and reverse phase-high performance liquid chromatography. HMW-AR1 and HMW-AR2 were found to possess complex or hybrid type N-linked oligosaccharide structures that contained sialic acid. Additionally, HMW-AR1 and HMW-AR2 contained the disaccharide, Galbeta(1-->3)GalNAc, linked to Ser/Thr residues. No carbohydrate moieties were detected in LMW-AR. Mapping of the peptide cores of these molecules using antipeptide antibodies revealed that HMW-AR1 and HMW-AR2 were intact molecules, whereas LMW-AR contained the EGF-like domain, but possessed a truncated NH2-terminal extension. LMW-AR, HMW-AR1, and HMW-AR2 were all found to be potent stimulators of DNA synthesis in MCF-10A human mammary epithelial cells. These results suggest that the NH2-terminal region of the AR molecule is not critical to the ability of AR to activate the EGF receptor tyrosine kinase. C1 HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,ONCOL GRP,LONDON W12 0HS,ENGLAND. RP JOHNSON, GR (reprint author), US FDA,DIV CYTOKINE BIOL,CELL BIOL LAB,HFM 511,BLDG 29A,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 49 TC 33 Z9 33 U1 2 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 5 PY 1993 VL 268 IS 25 BP 18835 EP 18843 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV659 UT WOS:A1993LV65900070 PM 8360173 ER PT J AU GRASELA, TH WALAWANDER, CA KENNEDY, DL JOLSON, HM AF GRASELA, TH WALAWANDER, CA KENNEDY, DL JOLSON, HM TI CAPABILITY OF HOSPITAL COMPUTER-SYSTEMS IN PERFORMING DRUG-USE EVALUATIONS AND ADVERSE DRUG EVENT MONITORING SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article DE COMPUTERS; DATA COLLECTION; DRUG SURVEILLANCE NETWORK; DRUG USE; DRUGS, ADVERSE REACTIONS; HOSPITALS; PHARMACY, INSTITUTIONAL, HOSPITAL AB A survey to determine the extent of computerization in key areas of hospitals, the information being collected in the databases, and the capabilities of the computer systems for performing adverse drug event monitoring and drug-use evaluations was conducted. The questionnaire was distributed to clinical pharmacists in the 500 hospitals composing the Drug Surveillance Network. In the majority of the 166 responding hospitals (>85%), the pharmacy department, clinical chemistry and hematology laboratories, patient admissions, and microbiology laboratory were computerized for data acquisition and management. The medical records and purchasing departments were computerized in a smaller proportion of hospitals (75% and 74%, respectively). In the majority of hospitals with a computerized pharmacy department (>78%), there was ready access to computer databases in other departments, but simultaneous querying of multiple databases was possible in only 30%. Patients could be identified according to diagnosis in 82% of the hospitals and according to medication received in 83%. More than 85% of responding hospitals had implemented spontaneous reporting systems for the identification of adverse drug events. Computers are widely used in hospitals participating in the Drug Surveillance Network, but a substantial effort is necessary to make these resources more useful and to standardize processes so that data may be pooled across institutions to deal with important public health concerns. C1 SUNY Buffalo, CTR PHARMACOEPIDEMIOL RES, BUFFALO, NY 14260 USA. US FDA, CTR DRUG EVALUAT & RES, OFF EPIDEMIOL & BIOSTAT, ROCKVILLE, MD 20857 USA. RP GRASELA, TH (reprint author), SUNY Buffalo, DEPT PHARM, 319 COOKE HALL, BUFFALO, NY 14260 USA. FU FDA HHS [FD-U-000741-01] NR 13 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD SEP PY 1993 VL 50 IS 9 BP 1889 EP 1895 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LV305 UT WOS:A1993LV30500015 PM 8135235 ER PT J AU KENNEDY, DL TANNER, LA BARASH, D GOETSCH, RA AF KENNEDY, DL TANNER, LA BARASH, D GOETSCH, RA TI NATIONAL ADVERSE DRUG EVENT REPORTING SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Note ID LABETALOL C1 US FDA,CTR DRUG EVALUAT & RES,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857. RP KENNEDY, DL (reprint author), US FDA,OFF COMMISSIONER,ROOM 14-62,HF-2,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD SEP PY 1993 VL 50 IS 9 BP 1913 EP 1914 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LV305 UT WOS:A1993LV30500020 PM 8135239 ER PT J AU GOSWAMI, BB KOCH, WH CEBULA, TA AF GOSWAMI, BB KOCH, WH CEBULA, TA TI DETECTION OF HEPATITIS-A VIRUS IN MERCENARIA-MERCENARIA BY COUPLED REVERSE TRANSCRIPTION AND POLYMERASE CHAIN-REACTION SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MESSENGER-RNA; QUANTITATION; AMPLIFICATION; SHELLFISH; STRAINS; CELLS AB Hepatitis A virus (HAV) is a major cause of infectious hepatitis in humans. In this respect, bivalve mollusks pose a major health concern because they are filter feeders and can concentrate the virus up to 900-fold from contaminated water. Detection of HAV has been hampered because wild-type HAV grows poorly if at all in cell culture. Here we describe a technique for the detection of HAV in shellfish based on reverse transcription coupled with the polymerase chain reaction. RNA is isolated from hard-shell clam tissue and reverse transcribed with avian myeloblastosis virus reverse transcriptase. A portion of the cDNA pool is then amplified with primers specific for HAV. In experiments with an in vitro-synthesized HAV transcript, we were able to detect HAV sequence in the presence of a 200-million-fold excess of shellfish RNA. When intact virus was added to shellfish tissue before the isolation of RNA, the method was capable of detecting 10 viral RNA molecules in a reaction mixture. RP GOSWAMI, BB (reprint author), US FDA,DIV MOLEC BIOL RES & EVALUAT,200 C ST SW,WASHINGTON,DC 20204, USA. NR 22 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 1993 VL 59 IS 9 BP 2765 EP 2770 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA LW040 UT WOS:A1993LW04000001 PM 8215351 ER PT J AU DAWISHA, SM GMELIGMEYLING, F STEINBERG, AD AF DAWISHA, SM GMELIGMEYLING, F STEINBERG, AD TI ASSESSMENT OF CLINICAL-PARAMETERS ASSOCIATED WITH INCREASED FREQUENCY OF MUTANT T-CELLS IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV UTRECHT HOSP,3511 GV UTRECHT,NETHERLANDS. US FDA,CDRH,ROCKVILLE,MD 20850. MITRE CORP,MCLEAN,VA 22101. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S183 EP S183 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600855 ER PT J AU LIEU, TS CAPRA, JD SONTHEIMER, RD NAKHASI, HL AF LIEU, TS CAPRA, JD SONTHEIMER, RD NAKHASI, HL TI AN AUTOANTIGENIC FORM OF HUMAN CALRETICULIN IS AN HY RNA AND RUBELLA RNA-BINDING PROTEIN SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UT,SW MED CTR,DALLAS,TX 75235. US FDA LABS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S241 EP S241 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601195 ER PT J AU MBAUYA, ALL PLOTZ, PH WILDER, RL MILLER, FW AF MBAUYA, ALL PLOTZ, PH WILDER, RL MILLER, FW TI INCREASED PREVALENCE OF AUTOIMMUNE-DISEASE IN 1ST DEGREE RELATIVES OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY (IIM) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD. US FDA,CBER,BETHESDA,MD 20014. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S255 EP S255 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601276 ER PT J AU RIDER, LG MILLER, FW TARGOFF, IN SAMAYOA, E LINDAHL, M SHERRY, DD WENER, MH PLOTZ, PH AF RIDER, LG MILLER, FW TARGOFF, IN SAMAYOA, E LINDAHL, M SHERRY, DD WENER, MH PLOTZ, PH TI MYOSITIS-SPECIFIC AUTOANTIBODIES (MSA) IN CHILDREN - A BROADENED SPECTRUM OF JUVENILE MYOSITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD. US FDA,CBER,WASHINGTON,DC 20204. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S258 EP S258 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81601295 ER PT J AU SCHWIETERMAN, WD ZAND, MS PLOTZ, PH MILLER, FW AF SCHWIETERMAN, WD ZAND, MS PLOTZ, PH MILLER, FW TI MISDIAGNOSIS OF IDIOPATHIC INFLAMMATORY MYOPATHY (IIM) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20014. RI Zand, Martin/A-8612-2015 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1993 VL 36 IS 9 SU S BP S118 EP S118 PG 1 WC Rheumatology SC Rheumatology GA MB816 UT WOS:A1993MB81600474 ER PT J AU MILLER, HI AF MILLER, HI TI PERCEPTION OF BIOTECHNOLOGY RISKS - THE EMOTIONAL DIMENSION SO BIO-TECHNOLOGY LA English DT Editorial Material RP MILLER, HI (reprint author), US FDA,OFF BIOTECHNOL,BETHESDA,MD 20014, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD SEP PY 1993 VL 11 IS 9 BP 1075 EP 1076 DI 10.1038/nbt0993-1075 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA LU957 UT WOS:A1993LU95700029 ER PT J AU DRAGUNSKY, E GARDNER, D TAFFS, R LEVENBOOK, I AF DRAGUNSKY, E GARDNER, D TAFFS, R LEVENBOOK, I TI TRANSGENIC PVR TG-1 MICE FOR TESTING OF POLIOVIRUS TYPE-3 NEUROVIRULENCE - COMPARISON WITH MONKEY TEST SO BIOLOGICALS LA English DT Article ID VACCINE; RECEPTOR; SEQUENCE RP DRAGUNSKY, E (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892, USA. NR 13 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD SEP PY 1993 VL 21 IS 3 BP 233 EP 237 DI 10.1006/biol.1993.1080 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA MM151 UT WOS:A1993MM15100007 PM 8117436 ER PT J AU HERMAN, EH FERRANS, VJ AF HERMAN, EH FERRANS, VJ TI TIMING OF TREATMENT WITH ICRF-187 AND ITS EFFECT ON CHRONIC DOXORUBICIN CARDIOTOXICITY SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article ID SYRIAN GOLDEN-HAMSTERS; (+/-)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE ICRF-187; ADRIAMYCIN CARDIOTOXICITY; DAUNORUBICIN; REDUCTION; PHARMACOKINETICS; PRETREATMENT; DAUNOMYCIN; TOXICITY; RATS AB Studies were conducted to evaluate whether the timing of administration of ICRF-187 [(+)-1,2-bis(3,5 dioxopiperazinyl-1-yl)propane] would influence the degree of cardioprotection provided by this agent against the development of doxorubicin-induced chronic cardiomyopathy. Beagle dogs (8.5-14 kg) received either doxorubicin alone (1.75 mg/kg, i. v., n = 8), doxorubicin (1.75 mg/kg) simultaneously with ICRF-187 (35 mg/kg, i. v., n = 8), or doxorubicin (1.75 mg/kg) followed 2 h later by ICRF-187 (35 mg/kg, n = 8). Control animals received ICRF-187 (35 mg/kg, n = 4) or saline (n = 4). All animals received a course of seven treatments, each given 3 weeks apart, and were killed 3 weeks after the last treatment. Semiquantitative grading of histologic sections of myocardium showed that as compared with animals treated with doxorubicin alone, the incidence and the severity of the doxorubicin-induced myocardial lesions were reduced in the two groups of animals given doxorubicin plus ICRF-187. However, protection was significantly better in dogs receiving ICRF-187 and doxorubicin simultaneously than in those given ICRF-187 2 h after doxorubicin. These observations were interpreted as indicating that the timing of administration of ICRF-187 with respect to that of doxorubicin is an important factor in determining the degree of cardioprotection and that there is a ''time window'' in which ICRF-187 exerts optimal effects. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP HERMAN, EH (reprint author), US FDA,DIV RES & TESTING,MOD 1 FACIL,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 29 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1993 VL 32 IS 6 BP 445 EP 449 DI 10.1007/BF00685888 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA LR870 UT WOS:A1993LR87000006 PM 8258192 ER PT J AU MANJANATHA, MG NEWTON, RK MITTELSTAEDT, RA VILLANI, GRD DECLOS, KB HEFLICH, RH AF MANJANATHA, MG NEWTON, RK MITTELSTAEDT, RA VILLANI, GRD DECLOS, KB HEFLICH, RH TI MOLECULAR ANALYSIS OF DNA-ADDUCTS AND HPRT MUTATIONS PRODUCED BY 6-NITROSOCHRYSENE IN CHINESE-HAMSTER OVARY CELLS SO CARCINOGENESIS LA English DT Article ID POLYMERASE CHAIN-REACTION; DIPLOID HUMAN FIBROBLASTS; EXCISION REPAIR; STRAND SPECIFICITY; ARISTOLOCHIC ACID; SEQUENCE-ANALYSIS; MAMMALIAN-CELLS; GENE; GUANINE; REPLICATION AB We have characterized the mutational spectrum of 6-nitrosochrysene in the hprt gene of Chinese hamster ovary (CHO-K1) cells and also examined the adducts formed by this compound in CHO-K1 cells by quantitative P-32-postlabeling analysis. Seventy percent of the identified mutations were simple basepair substitutions, and they occurred more often at A:T (14/17) than at G:C. Furthermore, 13 of the basepair substitutions at A:T had the mutated dA, the probable adducted residue, on the non-transcribed DNA strand. The preference for mutation at A:T contrasted sharply with the distribution of adducts formed by 6-nitrosochrysene: 80% of the identified adducts were with dG, while only 20% were probably formed through binding with dA. Analyses conducted with excision-repair-defective CHO-UV5 cells revealed both a preference for basepair substitution at A:T and an adduct profile that were similar to those found for repair-proficient CHO-K1 cells. However, basepair substitutions from CHO-UV5 cell mutants had the mutated dAs distributed randomly between the non-transcribed and transcribed DNA strands. The mutational spectra found for solvent control CHO-K1 and CHO-UV5 cells differed from those of the 6-nitrosochrysene-treated cultures. These findings suggest that 6-nitrosochrysene-induced mutations are targeted to DNA damage, but that 6-nitrosochrysene-derived dA adducts are much more effective at producing mutations than 6-nitrosochrysene-derived dG adducts. The extreme strand bias for mutated dAs in the CHO-K1 mutational spectrum appears to result from preferential removal of 6-nitrosochrysene-induced DNA lesions from the transcribed DNA strand. C1 NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. UNIV NAPLES,DIPARTIMENTO BIOCHIM & BIOTECNOL MED,I-80138 NAPLES,ITALY. RP MANJANATHA, MG (reprint author), NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079, USA. NR 44 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1993 VL 14 IS 9 BP 1863 EP 1870 DI 10.1093/carcin/14.9.1863 PG 8 WC Oncology SC Oncology GA LY804 UT WOS:A1993LY80400022 PM 8403211 ER PT J AU FU, PP WU, YS VONTUNGELN, LS LAI, JS CHIARELLI, MP EVANS, FE AF FU, PP WU, YS VONTUNGELN, LS LAI, JS CHIARELLI, MP EVANS, FE TI SYNTHESIS OF 3-NITROBENZO[A]PYRENE BAY-REGION TRANS-7,8-DIOL ANTI-9,10-EPOXIDE AND THE CORRESPONDING N(2)-DEOXYGUANOSINE ADDUCT SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Note ID POLYCYCLIC AROMATIC-HYDROCARBONS; HAMSTER OVARY CELLS; SALMONELLA-TYPHIMURIUM; MUTAGENICITY; MONONITROBENZOPYRENES; 1-NITROBENZOPYRENE; METABOLISM; ACTIVATION AB 3-Nitrobenzo[a]pyrene (3-nitro-BaP) is a potent mutagenic environmental contaminant, and its biological activities have been intensively studied. It is significant to prepare its reactive metabolites and the corresponding modified DNA adducts for biological studies. The synthesis of its oxidized proximate metabolite trans-7,8-dihydroxy-7,8-dihydro-3-nitrobenzo[a]pyrene (3-nitro-BaP-trans-7,8-dihydrodiol, 1), its oxidized ultimate metabolite trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-3-nitrobenzo[a]pyrene (3-nitro-BaP-DE, 2), and the corresponding DNA adduct 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-3-nitrobenzo[a]pyrene is described. C1 PROVIDENCE UNIV, INST APPL CHEM, TAICHUNG, TAIWAN. RP FU, PP (reprint author), NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. NR 18 TC 11 Z9 11 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP-OCT PY 1993 VL 6 IS 5 BP 603 EP 608 DI 10.1021/tx00035a003 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA LY693 UT WOS:A1993LY69300003 PM 8292736 ER PT J AU ILETT, KF CASTLEDEN, WM VANDONGEN, YK STACEY, MC BUTLER, MA KADLUBAR, FF AF ILETT, KF CASTLEDEN, WM VANDONGEN, YK STACEY, MC BUTLER, MA KADLUBAR, FF TI ACETYLATION PHENOTYPE AND CYTOCHROME-P450IA2 PHENOTYPE ARE UNLIKELY TO BE ASSOCIATED WITH PERIPHERAL ARTERIAL-DISEASE SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID METABOLISM; SMOKING; CANCER AB The hypothesis that cytochrome P450IA2 (CYPIA2) and/or N-acetyltransferase 2 (NAT2) may be involved in the pathogenesis of peripheral arterial disease was investigated in 90 Australian patients with significant disease and 81 matched control subjects. CYPLA2 and NAT2 phenotypes were determined from urinary metabolite patterns after an oral dose of caffeine. NAT2 phenotype was similar (chi2 = 0.01; p = 0.98) in both atherosclerotic patients (43.3% rapid) and control subjects (42.0% rapid). CYPIA2 metabolism as measured by the median ratio of (1,7-dimethylxanthine + 1,7-dimethyluric acid)/caffeine was significantly induced by smoking in both patients with atherosclerosis (ratio of 6.5 in nonsmokers and 12.4 in smokers; p < 0.05) and control subjects (ratio of 8.2 in nonsmokers and 14.8 in smokers; p < 0.05), but values in atherosclerotic and control nonsmokers and smokers were similar. Probit transformation of the data revealed a trimodal distribution of ratios in control subjects who were nonsmokers, with 5% classified as poor metabolizers (homozygous rapid) and 95% as extensive metabolizers. The distribution of ratios in control subjects who were smokers was unimodal, whereas among the patients with arterial disease, both smokers and nonsmokers exhibited a bimodal pattern with 8.2% to 16% poor metabolizer and 84% to 91.8% extensive metabolizer phenotypes. When data from both nonsmokers and smokers were combined, the overall proportion of subjects who were poor metabolizers was not significantly different (chi2 = 1.82; p = 0.18) between control subjects (3.8%) and patients with atherosclerosis (10.6%). Thus biotransformation of environmental or dietary aromatic or heterocyclic amines by NAT2 or CYPIA2 is unlikely to have a significant role in the cause or pathogenesis of peripheral arterial disease. C1 UNIV WESTERN AUSTRALIA,DEPT SURG,NEDLANDS,WA 6009,AUSTRALIA. NATL CTR TOXICOL RES,OFF RES,JEFFERSON,AR 72079. RP ILETT, KF (reprint author), UNIV WESTERN AUSTRALIA,DEPT PHARMACOL,NEDLANDS,WA 6009,AUSTRALIA. NR 13 TC 21 Z9 22 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 SEP PY 1993 VL 54 IS 3 BP 317 EP 322 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MA072 UT WOS:A1993MA07200012 PM 8375127 ER PT J AU RAFII, F CERNIGLIA, CE AF RAFII, F CERNIGLIA, CE TI LOCALIZATION OF THE AZOREDUCTASE OF CLOSTRIDIUM-PERFRINGENS BY IMMUNOELECTRON MICROSCOPY SO CURRENT MICROBIOLOGY LA English DT Note ID HUMAN INTESTINAL MICROFLORA; AZO DYES; BACTERIA; REDUCTION AB An antibody against Clostridium perfringens azoreductase was used with protein A (gold-labeled) to locate the site of synthesis of extracellular azoreductase in this bacterium. Electron microscopy of immunogold-stained thin sections of C. perfringens cells showed an average of 134 gold particles per cell, distributed throughout the cytoplasm and not associated with any organized structures. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 9 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD SEP PY 1993 VL 27 IS 3 BP 143 EP 145 DI 10.1007/BF01576011 PG 3 WC Microbiology SC Microbiology GA LQ024 UT WOS:A1993LQ02400004 PM 23835747 ER PT J AU NYMAN, PJ PERFETTI, GA JOE, FL DIACHENKO, GW AF NYMAN, PJ PERFETTI, GA JOE, FL DIACHENKO, GW TI COMPARISON OF 2 CLEANUP METHODOLOGIES FOR THE GAS-CHROMATOGRAPHIC MASS-SPECTROMETRIC DETERMINATION OF LOW NANOGRAM GRAM LEVELS OF POLYNUCLEAR AROMATIC-HYDROCARBONS IN SEAFOOD SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE SEAFOOD; POLYNUCLEAR AROMATIC HYDROCARBONS; GAS CHROMATOGRAPHY; MASS SPECTROMETRY; PERCENT RECOVERY AB The March 1989 oil spill in Alaska prompted the Food and Drug Administration (FDA) to conduct a thorough investigation of clean-up methodologies aimed at determining low ng/g (ppb) levels of polynuclear aromatic hydrocarbons (PAHs) in seafood. The clean-ups from a modified FDA method and a National Marine Fisheries Service (NMFS) method were evaluated on the basis of the determination of 18 PAHs at levels ranging from 1 to 5 ppb by gas chromatography/mass spectrometry. In the modified FDA method, seafood extracts were purified by a liquid-liquid partition followed by a three-step elution through silica, alumina, and C18 solid-phase extraction cartridges. In the NMFS method, seafood extracts were purified by column chromatography through a deactivated silica gel/alumina column and a gel permeation high performance liquid chromatography column. Both methods quantitated 18 PAHs at levels ranging from 1 to 5 ppb. With the exception of naphthalene, average recoveries based on internal deuterated standards ranged from 73 to 144% for the modified FDA method and 63 to 106% for the NMFS method. RP NYMAN, PJ (reprint author), US FDA,DIV PROD MANUFACTURE & USE,WASHINGTON,DC 20204, USA. NR 0 TC 17 Z9 17 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD SEP-OCT PY 1993 VL 10 IS 5 BP 489 EP 501 PG 13 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA LW730 UT WOS:A1993LW73000002 PM 8224318 ER PT J AU JACOBS, RM YESS, NJ AF JACOBS, RM YESS, NJ TI SURVEY OF IMPORTED GREEN COFFEE BEANS FOR PESTICIDE-RESIDUES SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE PESTICIDE RESIDUES; COFFEE BEANS; CONTAMINANT MONITORING AB The US Food and Drug Administration carries out incidence/level monitoring in order to acquire data on the presence and amounts of pesticide residues in particular commodity/chemical combinations. In the survey reported here, imported green coffee beans were analysed for a variety of pesticide chemicals. A total of 60 green coffee samples were collected from 21 countries that are major exporters of coffee to the United States. The samples were analysed for organochlorine/organophosphorus, N-methyl carbamate, benomyl group and EBDC residues. Four samples had detectable residues: chlorpyrifos, 0.01, 0.02 and 0.04 ppm and pirimiphos-methyl, 0.01 ppm. The majority (93%) of the green coffee samples analysed in this survey had no detectable pesticide residues. RP JACOBS, RM (reprint author), US FDA,50 UN PLAZA FED OFF BLDG,SAN FRANCISCO,CA 94102, USA. NR 0 TC 3 Z9 3 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD SEP-OCT PY 1993 VL 10 IS 5 BP 575 EP 577 PG 3 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA LW730 UT WOS:A1993LW73000009 PM 8224325 ER PT J AU AKATSUKA, T DONETS, M SCAGLIONE, L CHING, WM SHIH, JWK DIBISCEGLIE, AM FEINSTONE, SM AF AKATSUKA, T DONETS, M SCAGLIONE, L CHING, WM SHIH, JWK DIBISCEGLIE, AM FEINSTONE, SM TI B-CELL EPITOPES ON THE HEPATITIS-C VIRUS NUCLEOCAPSID PROTEIN DETERMINED BY HUMAN MONOSPECIFIC ANTIBODIES SO HEPATOLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; EPSTEIN-BARR VIRUS; CHRONIC NON-A; AMINO-ACID; ANTIGENIC DETERMINANTS; PEPTIDE-SYNTHESIS; GENOME; IDENTIFICATION; ORGANIZATION; ENVELOPE AB Four monospecific antibodies against the hepatitis C virus nucleocapsid protein, which was expressed by recombinant baculovirus, were obtained by Epstein-Barr virus transformation of B cells from three patients with chronic hepatitis C virus infection. One of these antibodies was IgG and the other three were IgM. Their specificities were characterized initially by enzyme-linked immunosorbent assay and immunoblotting against hepatitis C virus proteins expressed by six recombinant baculoviruses with different hepatitis C virus sequence insertions. These specificities were confirmed, and their epitopes were more precisely determined with a series of overlapping decapeptides made by solid-phase pin technology. Two antibodies (1F4 and 2G6) reacted with the same peptides located near the amino(N)-terminus of nucleocapsid protein (amino acids 33-50). The third antibody (3B5) recognized the peptide consisting of amino acids 133-142, and the fourth antibody (3B9) was mapped to the carboxy(C)-terminus and reacted with a peptide consisting of amino acids 165-174. This epitope has not previously been reported. Two antibodies, 1F4 and 3B9, which are specific to the N-terminus and C-terminus of nucleocapsid protein, respectively, have been stably produced for more than 6 mo and are being subcloned to establish monoclonality. These antibodies should be useful reagents for the study of hepatitis C virus. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,HEPATITIS RES LAB,BLDG 29A,ROOM 1D14,BETHESDA,MD 20892. NIDDKD,DEPT TRANSFUS MED CLIN MED,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. USN,MED RES INST,BETHESDA,MD 20814. NR 33 TC 23 Z9 23 U1 0 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 SEP PY 1993 VL 18 IS 3 BP 503 EP 510 DI 10.1016/0270-9139(93)90348-Q PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LV018 UT WOS:A1993LV01800005 PM 7689529 ER PT J AU GOLDBERG, AM FRAZIER, JM BRUSICK, D DICKENS, MS FLINT, O GETTINGS, SD HILL, RN LIPNICK, RL RENSKERS, KJ BRADLAW, JA SCALA, RA VERONESI, B GREEN, S WILCOX, NL CURREN, RD AF GOLDBERG, AM FRAZIER, JM BRUSICK, D DICKENS, MS FLINT, O GETTINGS, SD HILL, RN LIPNICK, RL RENSKERS, KJ BRADLAW, JA SCALA, RA VERONESI, B GREEN, S WILCOX, NL CURREN, RD TI FRAMEWORK FOR VALIDATION AND IMPLEMENTATION OF IN-VITRO TOXICITY TESTS SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE ALTERNATIVES; IN-VITRO TOXICOLOGY; VALIDATION; TOXICITY TESTING; RISK ASSESSMENT ID EYE IRRITATION TEST; REGULATORY ACCEPTANCE; TOXICOLOGY; PROJECT AB The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering the validation of new methods is essential for the effective transfer of new technologic developments from the research laboratory into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks, a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects and endpoints of toxicity testing, and representing the academic, industrial, and regulatory communities, is recommended. Test validation acceptance is contingent on broad buy-in by disparate groups in the scientific community-academics, industry, and government. This is best achieved by early and frequent communication among parties and agreement on common goals. It is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction, and refinement alternatives in toxicity testing. C1 HAZLETON LABS,VIENNA,VA 22182. AVON PROD INC,SUFFERN,NY 10901. BRISTOL MYERS SQUIBB CO,SYRACUSE,NY 13221. COSMET TOILETRY & FRAGRANCE ASSOC INC,WASHINGTON,DC 20036. US EPA,WASHINGTON,DC 20460. EXXON BIOMED SCI INC,REHOBOTH BEACH,DE 19971. US FDA,LAUREL,MD 20708. US EPA,HLTH EFFECTS RES LAB,RES TRIANGLE PK,NC 27709. MICROBIOL ASSOCIATES INC,ROCKVILLE,MD 20850. RP GOLDBERG, AM (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR ALTERNAT ANIM TESTING,615 N WOLFE ST,BALTIMORE,MD 21218, USA. NR 34 TC 10 Z9 10 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI UPPER MARLBORO PA 9315 LARGO DR W #255, UPPER MARLBORO, MD 20774-4755 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SEP PY 1993 VL 29 IS 9 BP 688 EP 692 PG 5 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA MD189 UT WOS:A1993MD18900005 PM 8407711 ER PT J AU TAYLOR, DN TROFA, AC SADOFF, J CHU, CY BRYLA, D SHILOACH, J COHEN, D ASHKENAZI, S LERMAN, Y EGAN, W SCHNEERSON, R ROBBINS, JB AF TAYLOR, DN TROFA, AC SADOFF, J CHU, CY BRYLA, D SHILOACH, J COHEN, D ASHKENAZI, S LERMAN, Y EGAN, W SCHNEERSON, R ROBBINS, JB TI SYNTHESIS, CHARACTERIZATION, AND CLINICAL-EVALUATION OF CONJUGATE VACCINES COMPOSED OF THE O-SPECIFIC POLYSACCHARIDES OF SHIGELLA-DYSENTERIAE TYPE-1, SHIGELLA-FLEXNERI TYPE-2A, AND SHIGELLA-SONNEI (PLESIOMONAS-SHIGELLOIDES) BOUND TO BACTERIAL TOXOIDS SO INFECTION AND IMMUNITY LA English DT Article ID SERUM ANTIBODIES; ESCHERICHIA-COLI; NATURAL IMMUNITY; LIPOPOLYSACCHARIDE; PROTECTION; IMMUNIZATION; ANTIGEN; INFECTIONS; VIRULENCE; CHILDREN AB The theoretic basis for developing conjugate vaccines, to induce immunoglobulin G (IgG) lipopolysaccharide (LPS) antibodies for the prevention of shigellosis, has been described (J. B. Robbins, C.-Y. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992). The O-specific polysaccharides (O-SPs) of Shigella dysenteriae type 1, S. flexneri type 2a, and S. sonnei were covalently bound to carrier proteins. Alone, the O-SPs were not immunogenic in mice. Conjugates of these O-SPs, injected into young outbred mice subcutaneously as saline solutions containing 2.5 mug of saccharide, elicited serum IgG and IgM antibodies with booster responses; adsorption onto alum enhanced their immunogenicity. Injection of 25 mug of these conjugates into adult volunteers elicited mild local reactions only. Each conjugate induced a significant rise of the geometric mean serum IgG, IgM, and IgA LPS antibody levels. A second injection 6 weeks later did not elicit booster responses, and adsorption of the conjugates onto alum did not enhance their immunogenicity. Conjugate-induced levels of IgA, but not IgG or IgM, declined to preimmunization levels at day 56. The levels of postimmunization antibodies of the three immunoglobulin classes were similar to or higher than those of recruits in the Israel Defense Force following shigellosis caused by S. flexneri type 2a or S. sonnei. These data provide the basis for evaluating these conjugates to prevent shigellosis. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20852. ISRAEL DEF FORCES,MED CORPS,TEL AVIV,ISRAEL. NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NIDDKD,CELLULAR & MOLEC BIOL LAB,BIOTECHNOL UNIT,BETHESDA,MD 20892. RP TAYLOR, DN (reprint author), WALTER REED ARMY INST RES,DIV COMMUNICABLE DIS & IMMUNOL,WASHINGTON,DC 20307, USA. NR 52 TC 109 Z9 115 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1993 VL 61 IS 9 BP 3678 EP 3687 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LU858 UT WOS:A1993LU85800014 PM 8359890 ER PT J AU PRICE, WD LOVELL, RA MCCHESNEY, DG AF PRICE, WD LOVELL, RA MCCHESNEY, DG TI NATURALLY-OCCURRING TOXINS IN FEEDSTUFFS - CENTER FOR VETERINARY-MEDICINE PERSPECTIVE SO JOURNAL OF ANIMAL SCIENCE LA English DT Article DE AFLATOXINS; VOMITOXIN; FUMONISIN; GOSSYPOL; GLUCOSINOLATES ID FUSARIUM-MONILIFORME; RISK ASSESSMENT; MYCOTOXINS; FUMONISINS; PRODUCTS; RESIDUES; REPRODUCTION; OCHRATOXIN; TOXICITY; GOSSYPOL AB The objectives of this review are to provide 1) information on the FDA Feed Contaminants Program, 2) the legal history of aflatoxins and their current action levels, 3) a report on the levels of aflatoxins, fumonisins, vomitoxin, ochratoxin A, and zearalenone in domestic and import surveillance samples of feed during fiscal years 1989 through 1992, and 4) information on naturally occurring toxins encountered recently by the Center for Veterinary Medicine. Ten of 644 (1.6%) domestic corn samples and 7 of 106 (6.6%) domestic cottonseed samples contained aflatoxins at levels > 300 ppb. The mean fumonisin level in the 1990 survey of 85 corn screening samples was 12.1 ppm, and the values ranged from 2.6 to 32 ppm. The mean vomitoxin levels in the 1991 survey of 207 winter wheat samples and 206 spring wheat samples was 2.4 and .9 ppm, respectively. Ochratoxin A was not detected in 168 samples. Zearalenone was detected at levels > .1 5 ppm in only 1 of 161 samples. Cottonseed containing 13,000 ppm gossypol was recently implicated in the deaths of dairy cows. Crambe meal and canola meal are sanctioned for use in feed with certain restrictions, including the levels of glucosinolates. The FDA is continuing its surveillance and will strive to provide guidance on the increasing number of naturally occurring toxins. RP PRICE, WD (reprint author), FDA,CTR VET MED,DIV ANIM FEEDS,ROCKVILLE,MD 20855, USA. NR 35 TC 53 Z9 58 U1 0 U2 9 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PD SEP PY 1993 VL 71 IS 9 BP 2556 EP 2562 PG 7 WC Agriculture, Dairy & Animal Science SC Agriculture GA LV193 UT WOS:A1993LV19300034 PM 8407668 ER PT J AU TANNER, JT BARNETT, SA MOUNTFORD, MK AF TANNER, JT BARNETT, SA MOUNTFORD, MK TI ANALYSIS OF MILK-BASED INFANT FORMULA - PHASE-IV - IODIDE, LINOLEIC-ACID, AND VITAMIN-D AND VITAMIN-K - UNITED-STATES-FOOD-AND-DRUG-ADMINISTRATION-INFANT FORMULA COUNCIL - COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION AB In 1982, the U.S. Food and Drug Administration, the Infant Formula Council and its member companies, contract laboratories, and other government laboratories began a study of analytical methods for the nutrients listed in the Infant Formula Act of 1980. Phases I, II, III, and V have been completed. The present report provides data on Phase IV, in which 13 laboratories collaboratively studied an ion-selective electrode method for analyzing iodide, a gas chromatographic method for linoleic acid, and 2 liquid chromatographic (LC) methods each for vitamins D and K. Data were insufficient to evaluate one each of the LC methods studied for vitamins K and D. The relative standard deviations (RSD) are sufficient for the nutrient levels found in infant formula. RSDs (%) for repeatability (RSD(r)) and reproducibility (RSD(R)), respectively, were as follows: iodide, 4.0-11.4 and 13.5-18.2; linoleic acid, 1.0-1.6 and 3.5-5.1; vitamin K1, 3.2-16.0 and 6.2-19.4; and vitamin D3, 4.2 and 35.0. The recommendation to adopt the method for vitamin D was supported by the results of a ministudy. All laboratories were capable of using these methods with little training. The methods for determination of iodide, linoleic acid, and vitamins D and K in ready-to-feed milk-based infant formula have been adopted first action by AOAC International. C1 TMS ANALYT SERV,INDIANAPOLIS,IN 46268. INFANT FORMULA COUNCIL,ATLANTA,GA 30342. RP TANNER, JT (reprint author), US FDA,DIV NUTR,WASHINGTON,DC 20204, USA. NR 9 TC 12 Z9 12 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1993 VL 76 IS 5 BP 1042 EP 1056 PG 15 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA MB199 UT WOS:A1993MB19900017 PM 8241809 ER PT J AU DAFT, JL AF DAFT, JL TI METHYL-BROMIDE DETERMINATION IN SELECTED FOODS BY HEADSPACE TECHNIQUE SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TABLE-READY FOODS; ETHYLENE DIBROMIDE; TRAP METHOD; RAPID-DETERMINATION; GRAIN PRODUCTS; WHOLE GRAINS; FRUIT-FLY; RESIDUES; PURGE; PESTICIDES AB A headspace method used earlier for determining methyl bromide (MB) in assorted nuts and peanut butters has been successfully applied to other foods that could potentially contain traces of this toxic fumigant. The foods tested include 63 off-the-shelf spices and seasonings, 83 table-ready items (grain-based, dried, or highly seasoned), 30 dried fruits and trail mixes, and 38 oil-based items (oil-seeds, cooking oils, or spicy oil-based dressings). Sample headspace gas is produced by blending less-than-or-equal-to 50 g sample in 250+/-50 mL aqueous solution in a sealed 1000 mL blender cup. After equilibration at 25-degrees-C, the headspace is sampled with a gas-tight syringe and injected into a dual column-dual detector gas chromatograph. One determination is made with a 20% OV-101 packed column and a Ni-63 electron capture detector (ECD), the other with a GS-Q wide-bore capillary column and a Hall electrolytic conductivity detector (HECD). Of the approximately 200 samples tested, none contained detectable MB residue at a quantitation limit <100 ng/g sample. All fortified samples yielded MB recovery. Samples were fortified at levels ranging from 78 to 3250 ng MB/g. Recoveries ranged from a mean high of 56% for spices and seasonings to a mean low of 30% for oil-based foods. The overall recovery and CV, including the results from assorted nuts and peanut butters, were 46 and 33%, respectively. RP DAFT, JL (reprint author), US FDA,DEPT HLTH & HUMAN SERV,KANSAS CITY DIST OFF,1009 CHERRY ST,KANSAS CITY,MO 64106, USA. NR 26 TC 4 Z9 4 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1993 VL 76 IS 5 BP 1083 EP 1091 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA MB199 UT WOS:A1993MB19900020 PM 8241812 ER PT J AU SNELL, RP AF SNELL, RP TI GAS-CHROMATOGRAPHIC DETERMINATION OF CYCLOHEXANONE LEACHED FROM HEMODIALYSIS TUBING SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PVC BAGS; TOXICITY AB A capillary gas chromatographic procedure is described for the determination of cyclohexanone leached from hemodialysis tubing by water. Recoveries were 100% at 2.0 mg/100 mL (20 ppm), 99.0% at 500 mug/100 m L (5 ppm), and 106% at 1.0 mug/100 mL (10 ppb). Reproducibility of the system was 0.152% for 3.0 muL injections of a solution containing cyclohexanone at 5.58 mug/mL. Correlation coefficients were 0.9983 for 0.3672-3.672 ng and 1.0000 for 3.672-367.2 ng. Twenty hemodialysis tubing sets from 4 manufacturers were examined. The leachable cyclohexanone ranged from 1.02 to 43.7 ppm per set. Rinsing the tubing with 1 L 0.9% sodium chloride solution did not remove significant amounts (P = 0.05) of leachable cyclohexanone. RP SNELL, RP (reprint author), US FDA,MINNEAPOLIS LAB MICROBIOL INVEST,240 HENNEPIN,MINNEAPOLIS,MN 55401, USA. NR 11 TC 10 Z9 10 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1993 VL 76 IS 5 BP 1127 EP 1132 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA MB199 UT WOS:A1993MB19900025 PM 8241816 ER PT J AU SACK, CA KENDALL, DC KRAUSE, RT AF SACK, CA KENDALL, DC KRAUSE, RT TI DETERMINATION OF METHYLENE-CHLORIDE ACCEPTABILITY AND ITS PURIFICATION FOR ETHYLENETHIOUREA METHODOLOGY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Note AB A liquid chromatographic-electrochemical method for the determination of ethylenethiourea (ETU) residues uses methylene chloride in the cleanup. Distilled-in-glass grade methylene chloride produced erratic ETU recoveries ranging from 0 to 106% for vacuum rotary evaporation of the solvent. ETU recoveries were found to be dependent on the bottle of methylene chloride used, not on supplier or lot. When GC2 grade methylene chloride from Burdick & Jackson Laboratories was used, ETU recoveries ranged from 92 to 110%. ''Acceptable'' ETU recoveries were defined as those values between 90 and 110%. Passing ''unacceptable'' methylene chloride through a column containing anhydrous sodium sulfate, sodium carbonate, and alumina was found to adequately purify methylene chloride. Treated methylene chloride provided acceptable ETU recoveries for up to 1 month after ''purification.'' C1 US FDA,DIV CONTAMINANTS CHEM,WASHINGTON,DC 20204. RP SACK, CA (reprint author), US FDA,TOTAL DIET RES CTR,KANSAS CITY,MO 64106, USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 1993 VL 76 IS 5 BP 1146 EP 1148 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA MB199 UT WOS:A1993MB19900029 PM 8241818 ER PT J AU GOGOLEWSKI, S JOVANOVIC, M PERREN, SM DILLON, JG HUGHES, MK AF GOGOLEWSKI, S JOVANOVIC, M PERREN, SM DILLON, JG HUGHES, MK TI TISSUE-RESPONSE AND IN-VIVO DEGRADATION OF SELECTED POLYHYDROXYACIDS - POLYLACTIDES (PLA), POLY(3-HYDROXYBUTYRATE) (PHB), AND POLY(3-HYDROXYBUTYRATE-CO-3-HYDROXYVALERATE) (PHB/VA) SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID HYDROXYBUTYRATE-HYDROXYVALERATE COPOLYMERS; BIODEGRADABLE MEDICAL DEVICES; MASSIVE POLY(ALPHA-HYDROXY ACIDS); STRUCTURE-PROPERTY RELATIONSHIPS; INVITRO DEGRADATION; HYDROLYTIC DEGRADATION; ALIPHATIC POLYESTERS; INTERNAL-FIXATION; RESORBABLE MATERIALS; PHYSICAL-PROPERTIES AB The tissue response and in vivo molecular stability of injection-molded polyhydroxyacids-polylactides (PLA), poly(3-hydroxybutyrate) (PHB), and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/VA, 5-22% VA content)-were studied. Polymers were implanted subcutaneously in mice and extirpated at 1, 3, and 6 months in order to study tissue response and polymer degradation. All polymers were well tolerated by the tissue. No acute inflammation, abscess formation, or tissue necrosis was observed in tissues adjacent to the implanted materials. Furthermore, no tissue reactivity or cellular mobilization was evident remote from the implant site. Mononuclear macrophages, proliferating fibroblasts, and mature vascularized fibrous capsules were typical of the tissue response. Degradation of the polymers was accompanied by an increase in collagen deposition. For the polylactide series, the inflammatory response after 1 month of implantation was less for materials containing the D-unit in the polymer chain, whereas in the case of the polyhydroxybutyrate/valerates, the number of inflammatory cells increased with increasing content of the valerate unit in the polymer chain. Between 1-3 months, there was slightly more tissue response to the PHB and PHB/VA polymers than to PLA. This response is attributed to the presence of leachable impurities and a low molecular weight soluble component in the polyhydroxybutyrate/valerates. At 6 months, the extent of tissue reaction was similar for both types of polymers. All polylactides degraded significantly (56-99%) by 6 months. For a poly(L-lactide) series, degradation rate in vivo decreased with increasing initial molecular weight of the injection-molded polymer. Several samples showed pronounced bimodal molecular weight distributions (MWD), which may be due to differences in degradation rate, resulting from variability in distribution of crystalline and amorphous regions within the samples. This may also be the result of two different mechanisms, i.e., nonenzymatic and enzymatic, which are involved in the degradation process, the latter being more extensive at the later stage of partially hydrolyzed polymer. The PHB and PHB/VA polymers degraded less (15-43%) than the polylactides following 6 months of implantation. Generally, the polymer with higher valerate content (19%, 22%) degraded most. The decrease in molecular weight was accompanied by a narrowing of the MWD for PHB and copolymers; there was no evidence of a bimodal MWD, possibly indicating that the critical molecular weight that would permit enzyme/polymer interaction had not been reached. Weight loss during implantation ranged from 0-50% for the polylactides, whereas for the PHB polymers weight loss ranged from 0-1.6%. (C) 1993 John Wiley & Sons, Inc. C1 US FDA,DIV MECH & MAT SCI,ROCKVILLE,MD 20552. RP GOGOLEWSKI, S (reprint author), AO ASIF RES INST,DEPT POLYMERS,CLAVADELERSTR,CH-7270 DAVOS,SWITZERLAND. NR 64 TC 347 Z9 354 U1 10 U2 63 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD SEP PY 1993 VL 27 IS 9 BP 1135 EP 1148 DI 10.1002/jbm.820270904 PG 14 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA LR717 UT WOS:A1993LR71700003 PM 8126012 ER PT J AU WOLFF, GL AF WOLFF, GL TI MULTIPLE LEVELS OF RESPONSE IN CARCINOGENICITY BIOASSAYS - REGULATIONAL VARIATION AMONG VIABLE YELLOW (A(VY)/-) MICE SO JOURNAL OF EXPERIMENTAL ANIMAL SCIENCE LA English DT Article ID COAT COLOR PATTERN; VY F1-HYBRID MICE; PHENOBARBITAL PROMOTION; MOUSE; EXPRESSION; GENE; HEPATOTUMORIGENESIS; SUSCEPTIBILITY; VARIABILITY; GENOTYPE AB Within genetically identical inbred and F1 hybrid test animal populations there exist subpopulations with different levels of sensitivity to induction of toxic endpoints, e.g., neoplasms, in response to toxicant exposure. These subpopulations differ from each other by other phenotypic characteristics as well. Presumably, these differences reflect alterations in the quantitative expression of some genes. These alterations are most probably directly or indirectly induced by subtle prenatal, neonatal or postnatal changes in endogenous microenvironmental conditions or factors. Such subpopulations have been identified within a population of agouti A/aunderbar and mottled yellow A(vy)underbar/Aunderbar (C3H x VY)F1 hybrid male mice. In these subpopulations differential body weight gain and formation of multiple liver adenomas in response to phenobarbital treatment were correlated with altered constitutive and inducible hepatic drug-metabolizing isozyme activities. These subpopulations could be identified by body weight as early as weaning age. In a different population of (YS x VY)F1 hybrid female mice. three phenotypes with different patterns of sensitivity to liver and lung tumor formation form visually separable phenotypic subpopulations by postnatal day 7. Two of these phenotYPes, obese mottled yellow and lean pseudoagouti, are genetically identical (genotype: A(vy)underbar/aunderbar). while the third phenotype, lean black a/aunderbar, differs from the others by just the A(vy)underbar allele. The yellow and pseudoagouti mice, fed lindane (gamma-hexachlorocyclohexane) for 24 months, differed with respect to liver tumor incidence but had similar incidences of lung tumors. In contrast, the black mice, fed lindane, were totally resistant to both types of tumors. Analyses of phenOtYPic variation within Other inbred or F1 hybrid populations have identified analogous subpopulations. In carcinogenicity assays this phenotypic variability can be used to mimic differential sensitivity to toxicant exposure among individuals in human populations. Data obtained from such phenotypic subpopulations should assist in improving risk assessment efforts. C1 UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT MOLEC BIOL & PHARMACOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT TOXICOL,LITTLE ROCK,AR 72205. RP WOLFF, GL (reprint author), NATL CTR TOXICOL RES,DIV NUTR TOXICOL,3900 NCTR RD,JEFFERSON,AR 72079, USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0939-8600 J9 J EXP ANIM SCI JI J. Exp. Anim. Sci. PD SEP PY 1993 VL 35 IS 5-6 BP 221 EP 231 PG 11 WC Zoology SC Zoology GA MB121 UT WOS:A1993MB12100005 PM 8218437 ER PT J AU MEHROTRA, PT WU, D CRIM, JA MOSTOWSKI, HS SIEGEL, JP AF MEHROTRA, PT WU, D CRIM, JA MOSTOWSKI, HS SIEGEL, JP TI EFFECTS OF IL-12 ON THE GENERATION OF CYTOTOXIC ACTIVITY IN HUMAN CD8+ T-LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-STIMULATORY FACTOR; NK CELLS; HETERODIMERIC CYTOKINE; MATURATION FACTOR; INTERFERON-GAMMA; PROLIFERATION; INDUCTION; PURIFICATION; RESPONSES AB We have studied the effects of human rIL-12 on the proliferation and generation of cytotoxic activity in human CTL precursors. Purified human blood CD8+ T lymphocytes were stimulated overnight with immobilized alpha-CD3 and cultured 3 to 4 additional days under various conditions. The addition of IL-1 2 resulted in a marked (10- to 20-fold), dose-dependent, augmentation of cytotoxicity per cell with a smaller (2-fold) increase in cell number. IL-12 augmentation of proliferation and cytotoxicity of CD8+ T cells was not inhibited by a mAb to the p55 subunit of the IL-2 receptor (alpha-Tac) at a concentration sufficient to block the activity of exogenously added IL-2, indicating that the activity of IL-12 did not require IL-2. Addition of IL-12 at the time of alpha-CD3 activation or 1 day later was highly effective at augmenting cytotoxicity, whereas delayed addition of IL-12 (day 2 or 3) resulted in a smaller increase in CTL activity with no increase in cell number. IL-12 at all doses tested synergized with low dose IL-2 in inducing the proliferation and differentiation of CD8+ T cells. The synergistic effect was not blocked by adding neutralizing serum to IFN-gamma. In contrast to this synergistic effect, IL-1 2 significantly inhibited the proliferation observed in the presence of higher concentrations of IL-2 (4,500 and 13,500 pg/ml). An inhibitory effect of IL-12 was also observed when IL-12 was added to CD8+ T lymphocytes 3 days subsequent to activation with alpha-CD3 and IL-2. This broad set of potent effects of IL-12 on CD8+ T cell responses suggests that IL-12 may play an important immunoregulatory role on CTL development in vivo and may be a useful tool for manipulating this process in vivo for investigational and immunotherapeutic purposes. RP MEHROTRA, PT (reprint author), US FDA,CTR BIOL & EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,CELLULAR IMMUNOL LAB HFM518,BETHESDA,MD 20892, USA. NR 28 TC 201 Z9 205 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1993 VL 151 IS 5 BP 2444 EP 2452 PG 9 WC Immunology SC Immunology GA LV434 UT WOS:A1993LV43400011 PM 8103066 ER PT J AU ELLNER, JJ HINMAN, AR DOOLEY, SW FISCHL, MA SEPKOWITZ, KA GOLDBERGER, MJ SHINNICK, TM ISEMAN, MD JACOBS, WR AF ELLNER, JJ HINMAN, AR DOOLEY, SW FISCHL, MA SEPKOWITZ, KA GOLDBERGER, MJ SHINNICK, TM ISEMAN, MD JACOBS, WR TI TUBERCULOSIS SYMPOSIUM - EMERGING PROBLEMS AND PROMISE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESISTANT MYCOBACTERIUM-TUBERCULOSIS; POLYMERASE CHAIN-REACTION; SHORT-COURSE CHEMOTHERAPY; AMPLIFICATION; DNA; IDENTIFICATION; INFECTION; OUTBREAK; INVITRO AB Between 1985 and 1991, 39,000 cases of tuberculosis occurred in excess of those expected based on previous trends. Immigration from high-prevalence countries, coinfection with human immunodeficiency virus (HIV), and outbreaks in congregative facilities are most responsible for the increase. Coincident with the increase in tuberculosis, outbreaks of multidrug resistant (MDR) tuberculosis have occurred. Clinical and epidemiologic data support nosocomial transmission. MDR tuberculosis occurred late in the course of HIV infection and was refractory to treatment. Compounding the problems of rising incidence and increasing resistance was the sudden recognition of shortages of antituberculous drugs. The problems currently posed by tuberculosis require new approaches to diagnosis and rapid sensitivity testing as well as assuring an adequate supply of licensed drugs and development of new drugs. A number of steps have been taken by governmental agencies to assure that the challenge is met. C1 CASE WESTERN RESERVE UNIV HOSP,CLEVELAND,OH 44106. CTR DIS CONTROL & PREVENT,ATLANTA,GA. UNIV MIAMI,SCH MED,MIAMI,FL 33152. JACKSON MEM HOSP,MIAMI,FL 33136. CORNELL UNIV,MED CTR,MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. US FDA,ROCKVILLE,MD 20857. NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO. RP ELLNER, JJ (reprint author), CASE WESTERN RESERVE UNIV,SCH MED,10900 EUCLID AVE,CLEVELAND,OH 44106, USA. NR 55 TC 101 Z9 105 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1993 VL 168 IS 3 BP 537 EP 551 PG 15 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LU337 UT WOS:A1993LU33700002 PM 8354898 ER PT J AU MCNEELY, MC LAWLEY, TJ HARVATH, L AF MCNEELY, MC LAWLEY, TJ HARVATH, L TI MONOCLONAL-ANTIBODY MODULATES HUMAN NEUTROPHIL CHEMOTAXIS TO N-FORMYL-METHIONYL-LEUCYL-PHENYLALANINE (FMLP) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; RESPIRATORY BURST; C5A RECEPTOR; ACTIVATION; ANTIGEN; MEMBRANE; PEPTIDES; ADHESION; PROTEINS AB Utilizing standard hybridoma techniques and a neutrophil chemotaxis assay for screening we produced a mouse monoclonal IgM antibody, 59/4, selected for specific inhibition of human neutrophil chemotaxis to the N-formyl-methionyl-leucyl-phenylalanine peptide (fMLP). Antibody 59/4 inhibited neutrophil chemotaxis to FMLP, but not human C5a or leukotriene B4. The antibody exhibited specific homogeneous binding to PMNs, heterogeneous binding to monocytes, and did not bind to lymphocytes in a pattern similar to the profile of N-formyl peptide binding in flow cytometric analysis. The antibody did not inhibit the binding of fluorescein-conjugated fMLPK or fML(H-3)P ligands to neutrophils in flow cytometric or competitive binding assays. Other neutrophil functions including myeloperoxidase release and rosette formation with immunoglobulin or immunoglobulin C3b-coated sheep erythrocytes were not affected in the presence of antibody 59/4. These results suggest that 59/4 specifically inhibits chemotaxis to fMLP. C1 EMORY UNIV,DEPT DERMATOL,ATLANTA,GA 30322. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,BETHESDA,MD 20014. RP MCNEELY, MC (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1993 VL 101 IS 3 BP 377 EP 382 DI 10.1111/1523-1747.ep12365592 PG 6 WC Dermatology SC Dermatology GA LX786 UT WOS:A1993LX78600025 PM 8396610 ER PT J AU CALVO, MS AF CALVO, MS TI DIETARY PHOSPHORUS, CALCIUM-METABOLISM AND BONE SO JOURNAL OF NUTRITION LA English DT Article DE HUMANS; PHOSPHORUS; CALCIUM; PARATHYROID HORMONE; BONE ID PARATHYROID-HORMONE SECRETION; SERUM CONCENTRATION; MINERAL CONTENT; PHOSPHATE; WOMEN; 1,25-DIHYDROXYVITAMIN-D; RATS; OSTEOPOROSIS; RESORPTION; BALANCE AB Many American women consume diets high in phosphorus and low in calcium. Concern about this dietary pattern stems from studies that show high phosphorus, low calcium intake causes secondary hyperparathyroidism and bone loss in several animal models. Recent studies in young adults have shown that a high phosphorus, moderately low calcium intake results in mild secondary hyperparathyroidism that persisted over 4 wk. However, plasma concentrations of the active form of vitamin D did not change in these subjects, despite stimulatory changes in parathyroid hormone and serum ionized calcium. Studies in normal adult men have shown that dietary phosphorus at levels within the observed normal range of intake can finely regulate the renal production and serum concentration of 1,25-dihydroxycholecalciferol. Thus, prolonged high phosphorus intake may impair the usual homeostatic mechanisms that are evoked when dietary calcium is limited. The current dietary patterns of high phosphorus, low calcium consumption result in persistent changes in the calcium regulating hormones that are not conducive to optimizing peak bone mass or slowing the rate of bone loss. RP CALVO, MS (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,HFS-226,WASHINGTON,DC 20204, USA. NR 59 TC 80 Z9 80 U1 1 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 1993 VL 123 IS 9 BP 1627 EP 1633 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LV455 UT WOS:A1993LV45500021 PM 8360792 ER PT J AU HANNA, GM LAUCAM, CA AF HANNA, GM LAUCAM, CA TI DETERMINATION OF CHLORPHENIRAMINE MALEATE IN TABLETS AND INJECTIONS BY H-1-NMR SPECTROSCOPY SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Note DE CHLORPHENIRAMINE MALEATE; DOSAGE FORMS; H-1-NMR SPECTROSCOPIC ASSAY ID LIQUID-CHROMATOGRAPHY; HYDROCHLORIDE; ION C1 ST JOHNS UNIV,COLL PHARM & ALLIED HLTH PROFESS,JAMAICA,NY 11439. US FDA,NEW YORK REG LAB,BROOKLYN,NY 11232. NR 23 TC 14 Z9 15 U1 0 U2 1 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 SEP PY 1993 VL 11 IS 9 BP 855 EP 859 DI 10.1016/0731-7085(93)80080-K PG 5 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA MA333 UT WOS:A1993MA33300012 PM 8218532 ER PT J AU SELVAM, MP MAYNER, RE BUCK, SM EPSTEIN, JS AF SELVAM, MP MAYNER, RE BUCK, SM EPSTEIN, JS TI A NOVEL, SENSITIVE RADIOIMMUNOPRECIPITATION ASSAY FOR THE DETECTION OF ANTIBODIES TO HUMAN IMMUNODEFICIENCY VIRUS-TYPE-2 SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-2; RIPA; WESTERN BLOT ID HTLV-III; AIDS PATIENTS; VIRUS; FEATURES; PROTEINS; HIV-2 AB A radioimmunoprecipitation assay that provides an alternative to the Western blot assay was developed for characterizing antibodies against human immunodeficiency virus type-2 (HIV-2). The assay is based on radioiodination of antigen using Bolton-Hunter reagent. The antigen consists of a soluble preparation of the NIH-Z (HIV-2) strain of 1000X purified virus spiked with purified recombinant HIV-2 gp105. Radiolabeled proteins were immunoprecipitated by immune human sera, even at the early stages of seroconversion. This new assay provides a simple method for characterizing and titrating antibodies against HIV-2. The method is more sensitive, and is more efficient than Western blotting. The labeled viral proteins are well suited for biochemical studies. RP SELVAM, MP (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,IMMUNOCHEM LAB,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 11 TC 1 Z9 1 U1 0 U2 2 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 SEP PY 1993 VL 44 IS 1 BP 1 EP 10 DI 10.1016/0166-0934(93)90002-9 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA LW368 UT WOS:A1993LW36800001 PM 8227273 ER PT J AU BERT, TM HESSELMAN, DM ARNOLD, WS MOORE, WS CRUZLOPEZ, H MARELLI, DC AF BERT, TM HESSELMAN, DM ARNOLD, WS MOORE, WS CRUZLOPEZ, H MARELLI, DC TI HIGH-FREQUENCY OF GONADAL NEOPLASIA IN A HARD CLAM (MERCENARIA SPP) HYBRID ZONE SO MARINE BIOLOGY LA English DT Article ID SOFT-SHELL CLAM; MYA-ARENARIA; HEMATOPOIETIC NEOPLASIA; AQUATIC ANIMALS; HYBRIDIZATION; GENETICS; CAMPECHIENSIS; SPECIATION; MORPHOLOGY; GROWTH AB The etiology of bivalve gonadal neoplasia has eluded invertebrate pathologists for over 20 yr. In a coastal Florida (USA) lagoon, where two species of hard clams (Mercenaria mercenaria and M. campechiensis) co-occur and hybridize, they exhibit a persistent, unusually high frequency of gonadal neoplasia. Hybridity, rather than environmental or other biological factors, appears to determine susceptibility, implicating a genetic mechanism in the etiology of the disease. However, the increase in frequency of occurrence of the disease in hybrids is not accompanied by an increase in severity beyond that experienced by pure-species genotypes, suggesting that only some components of the genetic mechanism are affected by hybridization. Differences between sexes in the overall and size-specific frequency of occurrence and in severity of the disease suggest that the genetic mechanism is associated with sex. The excessive susceptibility of hybrid genotypes to gonadal neoplasia results in reduced hybrid fitness and constitutes an unambiguous example of a cellular disease that acts as a barrier to gene flow between species. Moreover, because these species are of commercial importance, fishery practices that promote hybridization are common and, over time, may reduce the fitness of natural populations. C1 US FDA,ATLANTA,GA 30309. WAYNE STATE UNIV,DEPT BIOL,DETROIT,MI 48202. RP BERT, TM (reprint author), FLORIDA MARINE RES INST,DEPT NAT RESOURCES,100 8TH AVE SE,ST PETERSBURG,FL 33701, USA. NR 43 TC 46 Z9 46 U1 0 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0025-3162 J9 MAR BIOL JI Mar. Biol. PD SEP PY 1993 VL 117 IS 1 BP 97 EP 104 DI 10.1007/BF00346430 PG 8 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA LZ806 UT WOS:A1993LZ80600010 ER PT J AU HATHCOCK, JN AF HATHCOCK, JN TI SAFETY LIMITS FOR NUTRIENT INTAKES - CONCEPTS AND DATA REQUIREMENTS SO NUTRITION REVIEWS LA English DT Review ID TOXICITY; NIACIN RP HATHCOCK, JN (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV SCI & APPL TECHNOL,OFF SPECIAL NUTR,LAUREL,MD 20708, USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD SEP PY 1993 VL 51 IS 9 BP 278 EP 285 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LZ382 UT WOS:A1993LZ38200006 PM 8247422 ER PT J AU KAUFFMAN, RE BANNER, W BERLIN, CM BLUMER, JL GORMAN, RL LAMBERT, GH WILSON, GS BENNETT, DR CORDERO, JF KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ TEMPLE, AR REIGART, JR ETZEL, RA GOLDMAN, LR HENDRICK, JG MOFENSON, HD SIMON, PR FALK, H MILLER, RW ROGAN, W JACKSON, RJ AF KAUFFMAN, RE BANNER, W BERLIN, CM BLUMER, JL GORMAN, RL LAMBERT, GH WILSON, GS BENNETT, DR CORDERO, JF KAUFMAN, P LICATA, SA TOMICH, P TROENDLE, G YAFFE, SJ COTE, CJ TEMPLE, AR REIGART, JR ETZEL, RA GOLDMAN, LR HENDRICK, JG MOFENSON, HD SIMON, PR FALK, H MILLER, RW ROGAN, W JACKSON, RJ TI USE OF CHLORAL HYDRATE FOR SEDATION IN CHILDREN SO PEDIATRICS LA English DT Editorial Material ID STRAND BREAKS; LIVER INVIVO; TRICHLOROETHYLENE; MOUSE; ANEUPLOIDY; INDUCTION; COHORT; TOXICITY; EXPOSURE; CANCER C1 AMER MED ASSOC,CHICAGO,IL 60610. CTR DIS CONTROL & PREVENT,ATLANTA,GA. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NIEHS,RES TRIANGLE PK,NC 27709. RI Goldman, Lynn/D-5372-2012 NR 35 TC 62 Z9 63 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 SEP PY 1993 VL 92 IS 3 BP 471 EP 473 PG 3 WC Pediatrics SC Pediatrics GA LV815 UT WOS:A1993LV81500028 ER PT J AU HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G DAUM, RS LEDBETTER, EO AF HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G DAUM, RS LEDBETTER, EO TI HAEMOPHILUS-INFLUENZAE TYPE-B CONJUGATE VACCINES - RECOMMENDATIONS FOR IMMUNIZATION WITH RECENTLY AND PREVIOUSLY LICENSED VACCINES SO PEDIATRICS LA English DT Editorial Material ID INFANT RHESUS-MONKEYS; ANTIBODY-RESPONSES; CHILDREN; EFFICACY; IMMUNOGENICITY; POLYSACCHARIDE; DISEASE; INFECTION; TRIAL C1 CTR DIS CONTROL,ATLANTA,GA 30333. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. UNIV CHICAGO,CHICAGO,IL 60637. RI Steele, Russell/A-6075-2011 NR 33 TC 8 Z9 9 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 SEP PY 1993 VL 92 IS 3 BP 480 EP 488 PG 9 WC Pediatrics SC Pediatrics GA LV815 UT WOS:A1993LV81500031 ER PT J AU HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G AF HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G TI USE OF RIBAVIRIN IN THE TREATMENT OF RESPIRATORY SYNCYTIAL VIRUS-INFECTION SO PEDIATRICS LA English DT Editorial Material ID CHILDREN; INFANTS; AEROSOL C1 CTR DIS CONTROL,ATLANTA,GA 30333. US FDA,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. RI Steele, Russell/A-6075-2011 NR 17 TC 54 Z9 54 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 SEP PY 1993 VL 92 IS 3 BP 501 EP 504 PG 4 WC Pediatrics SC Pediatrics GA LV815 UT WOS:A1993LV81500037 ER PT J AU NASR, MM AF NASR, MM TI SINGLE-PUFF PARTICLE-SIZE ANALYSIS OF ALBUTEROL METERED-DOSE INHALERS (MDIS) BY HIGH-PRESSURE LIQUID-CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION (HPLC-EC) SO PHARMACEUTICAL RESEARCH LA English DT Article DE ALBUTEROL; METERED-DOSE INHALER; HPLC-EC; SINGLE PUFF; PARTICLE-SIZE ANALYSIS; ELECTROCHEMICAL DETECTION ID AEROSOLS RP NASR, MM (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ROOM 1002,ST LOUIS,MO 63101, USA. NR 15 TC 8 Z9 8 U1 0 U2 0 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 SEP PY 1993 VL 10 IS 9 BP 1381 EP 1384 DI 10.1023/A:1018994418999 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA LV524 UT WOS:A1993LV52400023 PM 8234180 ER PT J AU WYSOWSKI, DK SCHOBER, SE WISE, RP KOPSTEIN, A AF WYSOWSKI, DK SCHOBER, SE WISE, RP KOPSTEIN, A TI MORTALITY ATTRIBUTED TO MISUSE OF PSYCHOACTIVE-DRUGS, 1979-88 SO PUBLIC HEALTH REPORTS LA English DT Article ID UNITED-STATES AB To assess mortality attributed to misuse of psychoactive drugs in the United States from 1979 through 1988, the authors obtained from death certificates the annual number of, and age-, sex-, and race-specific data for, deaths in which psychoactive drugs were coded as the underlying or contributing cause. Deaths with psychoactive drugs specified as underlying cause (drug-induced) increased from 6,500 (2.9 per 100,000) in 1979 to more than 10,000 (3.8 per 100,000) in 1988. Deaths with psychoactive drugs specified as either underlying or contributing cause (drug-related) increased from 7,200 (3.2 per 100,000) in 1979 to more than 14,400 (5.5 per 100,000) in 1988. The drugs that primarily accounted for this increase were illicit, in particular, the opiates (heroin) and cocaine, with most of the remainder accounted for by misuse of various legal drugs. The largest increases between 1979 and 1988 occurred among black men ages 35-44 whose drug-induced death rates rose from 8 to 36 per 100,000 and whose drug-related death rates from 10 to 82 per 100,000. These data identify a high-risk group for targeting efforts to prevent deaths due to misuse of psychoactive drugs. C1 US FDA,CTR DRUG EVALUAT,DIV EPIDEMIOL & PREVENT RES,ROCKVILLE,MD 20857. NR 11 TC 20 Z9 20 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 1993 VL 108 IS 5 BP 565 EP 570 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MB699 UT WOS:A1993MB69900007 PM 8416115 ER PT J AU BACKINGER, CL BRUERD, B KINNEY, MB SZPUNAR, SM AF BACKINGER, CL BRUERD, B KINNEY, MB SZPUNAR, SM TI KNOWLEDGE, INTENT TO USE, AND USE OF SMOKELESS TOBACCO AMONG 6TH GRADE SCHOOLCHILDREN IN 6 SELECTED UNITED-STATES SITES SO PUBLIC HEALTH REPORTS LA English DT Article ID CIGARETTE-SMOKING; ADOLESCENTS; PATTERNS; CHILDREN; SNUFF; PREVALENCE; NICOTINE; POPULATION; UNIVERSITY; NORTHWEST AB Questionnaires on smokeless tobacco use were completed by 781 sixth grade students in 15 schools at six locations in the United States. The students were both American Indian-Alaska Native and non-American Indian-Alaska Native. The Indian and Alaska Native schoolchildren were experimenting with and regularly using smokeless tobacco at higher rates that non-Indian schoolchildren. At Indian Health Service sites, 28.1 percent of the children reported current use of smokeless tobacco, compared with 3.3 percent of the children elsewhere. For girls reporting smokeless tobacco experimentation, the comparison was 68.9 percent at Indian Health Service sites and 8.7 percent at non-Indian sites; for boys, it was 79.1 percent from the Indian sites and 35.4 percent from the non-Indian sites. For those students who had tried smokeless tobacco, more than half also reported having tried cigarettes. The majority of all sixth grade students surveyed were aware of the health risks of smokeless tobacco use in that it is an increased risk for cancer. Additional research is needed to determine appropriate interventions. C1 INDIAN HLTH SERV,SALEM,OR. UNIV MICHIGAN,SCH PUBL HLTH,PROGRAM DENT PUBL HLTH,ANN ARBOR,MI 48109. RP BACKINGER, CL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF TRAINING & ASSISTANCE,ROCKVILLE,MD 20857, USA. NR 42 TC 5 Z9 5 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 1993 VL 108 IS 5 BP 637 EP 642 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MB699 UT WOS:A1993MB69900015 PM 8210262 ER PT J AU DUHART, HM FOGLE, CM GILLAM, MP BAILEY, JR SLIKKER, W PAULE, MG AF DUHART, HM FOGLE, CM GILLAM, MP BAILEY, JR SLIKKER, W PAULE, MG TI PHARMACOKINETICS OF COCAINE IN PREGNANT AND NONPREGNANT RHESUS-MONKEYS SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE COCAINE; BENZOYLECGONINE; NORCOCAINE; PREGNANT; NONPREGNANT; MONKEY; PHARMACOKINETICS; INTRAMUSCULAR ID LIQUID-CHROMATOGRAPHY; HUMANS; INTRANASAL; KINETICS AB To determine pharmacokinetic parameters for cocaine in rhesus monkey plasma, samples were taken over several hours after i.m. administration of cocaine plus a tritiated cocaine tracer. Cocaine and its metabolites, benzoylecgonine and norcocaine, were isolated via HPLC and quantitated using liquid scintillation spectrometry. Pregnant subjects were dosed with cocaine at 0.3 (n = 3) or 1.0 (n = 3) mg/kg, whereas nonpregnant female subjects were dosed with 1.0 mg/kg (n = 3). For the pregnant subjects, pharmacokinetic studies were conducted on about gestational day 125 and areas under the concentration versus time curve (AUCs, ng/mL x h) were 64 +/- 26 (+/- SEM) and 143 +/- 12; half-lives (t1/2s, h) were 1.9 +/- 0.6 and 1.1 +/- 0.1 after 0.3 and 1.0 mg/kg i.m., respectively. For nonpregnant subjects dosed acutely with 1.0 mg/kg, the AUC was 262 +/- 63 and the t1/2 Was 1.4 +/- 0.3. There appear to be few differences in the pharmacokinetic parameters of cocaine and benzoylecgonine between pregnant and nonpregnant monkeys in this study. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,3900 NCTR RD,HFT-132,JEFFERSON,AR 72079. FU PHS HHS [224-89-0003] NR 21 TC 18 Z9 18 U1 1 U2 1 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 SEP-OCT PY 1993 VL 7 IS 5 BP 429 EP 437 DI 10.1016/0890-6238(93)90087-N PG 9 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA MC739 UT WOS:A1993MC73900004 PM 8274818 ER PT J AU BRODEUR, BR MARTIN, D HAMEL, J SHAHIN, RD LAFERRIERE, C AF BRODEUR, BR MARTIN, D HAMEL, J SHAHIN, RD LAFERRIERE, C TI ANTIGENIC ANALYSIS OF THE SACCHARIDE MOIETY OF THE LIPOOLIGOSACCHARIDE OF BORDETELLA-PERTUSSIS SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID VIRULENCE FACTORS; ANTIBODY-LEVELS; LIPOPOLYSACCHARIDES; IMMUNIZATION; ENDOTOXIN; CHILDREN; COLONIZATION; MODULATION; PROTEINS; VARIANTS C1 US FDA,CTR BIOL EVALUAT,BETHESDA,MD 20892. RP BRODEUR, BR (reprint author), NATL LAB IMMUNOL,CTR DIS CONTROL LAB,HPB BLDG 7,TUNNEYS PASTURE,OTTAWA K1A OL2,ON,CANADA. NR 52 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD SEP PY 1993 VL 15 IS 2-3 BP 205 EP 215 PG 11 WC Immunology; Pathology SC Immunology; Pathology GA LY080 UT WOS:A1993LY08000008 PM 8256198 ER PT J AU CUFF, JM KIMMEL, GL HEREDIA, DJ TUDOR, N CHEN, J KIMMEL, CA AF CUFF, JM KIMMEL, GL HEREDIA, DJ TUDOR, N CHEN, J KIMMEL, CA TI RELATIONSHIP BETWEEN ABNORMAL SOMITE DEVELOPMENT AND AXIAL SKELETAL DEFECTS IN RATS FOLLOWING HEAT EXPOSURE SO TERATOLOGY LA English DT Article ID CHICK-EMBRYO; SEGMENTAL ANOMALIES; DEVELOPMENT INVITRO; SHOCK; HYPERTHERMIA; CELLS AB The effects of in vivo heat exposure on gestation day (GD) 10 rat embryos were evaluated on GD 11 to determine the relationships between morphological sequelae following in vivo and in vitro exposures and between effects detected on GD 11 and those observed in postnatal day (PND) 3 pups. Anesthetized rats were exposed to 42-degrees-C in a warm air incubator until their rectal temperatures reached 41-degrees-C or until a rectal temperature of 42-42.5-degrees-C had been maintained for 5 minutes. Heat-exposed embryos exhibited a significant decrease in growth parameters including head length, somite number, and protein content/embryo versus controls. These changes correlated well with in vitro effects from an earlier study (G.L. Kimmel et al., '93). Among the morphological endpoints which were slightly delayed in development were the caudal neural tube, branchial bars, forelimb and hindlimb. The only effect on the embryos that could not be explained as a transient delay in development induced by heat was the induction of unsegmented somites. Additional embryos were exposed to 42-degrees-C for 15-20 min in vitro and examined specifically for unsegmented somites, which were observed in 47% of embryos exposed to 42-degrees-C in vivo or in vitro. This phenomenon was observed in somites 9-20, i.e., those that give rise to cervical and thoracic vertebrae and ribs. These results correlated well with the axial skeletal malformations observed in PND 3 pups exposed to the same heat treatment (C.A. Kimmel et al., '93). (C) 1993 Wiley-Liss, Inc. C1 US EPA,REPROD & DEV TOXICOL BRANCH RD689,401 M ST SW,WASHINGTON,DC 20460. THIEL COLL,DEPT BIOL,GREENVILLE,PA 16125. US FDA,CTR DEVICES & RADIOL HLTH,DIV BIOMETR SCI,STAT BRANCH,ROCKVILLE,MD 20857. US FDA,DIV LIFE SCI,HLTH SCI BRANCH,ROCKVILLE,MD 20857. BIOCON INC,ROCKVILLE,MD 20857. NR 22 TC 18 Z9 18 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 0040-3709 J9 TERATOLOGY JI Teratology PD SEP PY 1993 VL 48 IS 3 BP 259 EP 266 DI 10.1002/tera.1420480309 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA LV519 UT WOS:A1993LV51900008 PM 8248863 ER PT J AU GOERING, PL FISHER, BR KISH, CL AF GOERING, PL FISHER, BR KISH, CL TI STRESS PROTEIN-SYNTHESIS INDUCED IN RAT-LIVER BY CADMIUM PRECEDES HEPATOTOXICITY SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID HEAT-SHOCK PROTEIN; IMMUNOCYTOCHEMICAL DETECTION; PRIMARY CULTURES; GENE-EXPRESSION; SODIUM ARSENITE; CELLS; INDUCTION; INVITRO; EXPOSURE; DISEASE RP GOERING, PL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,DIV LIFE SCI,ROCKVILLE,MD 20857, USA. NR 71 TC 83 Z9 85 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD SEP PY 1993 VL 122 IS 1 BP 139 EP 148 DI 10.1006/taap.1993.1181 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LY074 UT WOS:A1993LY07400017 PM 8378928 ER PT J AU BRADSHAW, PA LO, J PERKINS, S FOUNG, SKH HADLOCK, KG GOH, CJ CHAN, L RUDA, M AF BRADSHAW, PA LO, J PERKINS, S FOUNG, SKH HADLOCK, KG GOH, CJ CHAN, L RUDA, M TI DETERMINATION OF IMMUNODOMINANT EPITOPE WITHIN HTLV-I GP21 SO TRANSFUSION LA English DT Meeting Abstract C1 STANFORD UNIV,CTR BLOOD,STANFORD,CA 94305. GENELABS TECHNOL INC,REDWOOD CITY,CA. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 1993 VL 33 IS 9 SU S BP S39 EP S39 PG 1 WC Hematology SC Hematology GA LZ447 UT WOS:A1993LZ44700147 ER PT J AU JARBOE, H TOTH, BR SHOEMAKER, KE GREENLEES, KJ KLEINOW, KM AF JARBOE, H TOTH, BR SHOEMAKER, KE GREENLEES, KJ KLEINOW, KM TI PHARMACOKINETICS, BIOAVAILABILITY, PLASMA-PROTEIN BINDING AND DISPOSITION OF NALIDIXIC-ACID IN RAINBOW-TROUT (ONCORHYNCHUS-MYKISS) SO XENOBIOTICA LA English DT Article ID OXOLINIC ACID; SALMO-GAIRDNERI; ANESTHESIA AB 1. The pharmacokinetics, disposition and bioavailability of nalidixic acid were examined in Rainbow Trout following i.v. and per os administration (5 mg/kg). 2. Nalidixic acid was biexponentially eliminated from plasma following i.v. dosing (t1/2alpha = 0.06 h, t1/2beta = 23.0 h). The volume of distribution (V(ss)) and total body clearance (Cl(b)) were 964.7 ml/kg and 31.5 ml/kg/h, respectively. 3. In vitro plasma protein binding was specific and saturable over a range of concentrations from 0.43 mum to 20.0 mM. Binding was approx. 26% at kinetically relevant plasma concentrations. 4. Apparent oral bioavailability was determined to be > 100%, suggesting that nalidixic acid was largely bioavailable and non-linear pharmacokinetics were evoked. 5. Oral studies demonstrated the highest C-14 nalidixic acid equivalent concentrations in bile, intestine and liver. Muscle contained intermediate concentrations but among all organs accounted for the greatest total amount of drug (12.2% of dose). Mass balance studies demonstrated composite values for per cent of dose administered of 23.7, 18.8, 8.5, 10.0, 7.4 and 2.3% for 1, 2, 3, 6, 9 and 15 days, respectively. 6. A glucuronic acid conjugate of nalidixic acid was identified by n.m.r. and mass spectral analysis as the single primary metabolite. C1 LOUISIANA STATE UNIV,SCH VET MED,DEPT VET PHYSIOL PHARMACOL & TOXICOL,BATON ROUGE,LA 70803. US FDA,COLL VET MED,ROCKVILLE,MD 20857. FU FDA HHS [U01 FD 01466] NR 27 TC 4 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD SEP PY 1993 VL 23 IS 9 BP 961 EP 972 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ME176 UT WOS:A1993ME17600001 PM 8291264 ER PT J AU BOTSTEIN, P AF BOTSTEIN, P TI IS QT INTERVAL PROLONGATION HARMFUL - A REGULATORY PERSPECTIVE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 1992 ANNUAL MEETING OF THE SYMP ON NEW DRUGS AND DEVICES - QT(C) INTERVAL PROLONGATION : IS IT BENEFICIAL OR HARMFUL CY OCT 29, 1992 CL PHILADELPHIA, PA SP MARION MERRELL DOW AB Drugs that prolong the QT interval may increase the risk of torsades de pointes, a potentially lethal ventricular arrhythmia. In recent years, spontaneous reports have highlighted these complications in patients receiving certain antihistamines (e.g., terfenadine or astemizole) or an agent for the treatment of incontinence (terodiline). Examination of these reports has revealed that hepatic disease or concomitant therapy with ketoconazole or macrolide antibiotics may increase the risk of QT prolongation or torsades in patients receiving terfenadine. In patients receiving astemizole, doses exceeding that recommended or concomitant therapy with ketoconazole or macrolide antibiotics have been implicated in the increased risk of these complications. With terodiline (which remains investigational in the United States), the risk of QT prolongation and torsades are of particular concern in the frail elderly, who are most likely to be treated with this agent. A possible explanation for the elevated risk may be marked increases in the elimination half-life and serum level of the drug in this group. The lessons learned from the experiences with these drugs hold implications for the future development of agents that prolong the QT interval and suggest the need for dose-response relation data and metabolic evaluations to define the subpopulations at particular risk. RP BOTSTEIN, P (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF DRUG EVALUAT 1,HFD 101,ROCKVILLE,MD 20857, USA. NR 0 TC 43 Z9 43 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B50 EP B52 DI 10.1016/0002-9149(93)90041-A PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800016 PM 8256756 ER PT J AU BOTSTEIN, P RODEN, D MOSS, A MOORE, EN AF BOTSTEIN, P RODEN, D MOSS, A MOORE, EN TI VARIABILITY IN QT INTERVAL SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 VANDERBILT UNIV,DIV CLIN PHARMACOL,NASHVILLE,TN 37232. UNIV PENN,PHILADELPHIA,PA 19104. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PREVENT & COMMUNITY MED,HEART RES FOLLOW UP PROGRAM,ROCHESTER,NY 14642. RP BOTSTEIN, P (reprint author), US FDA,CTR DRUG EVALUAT & RES,OFF DRUG EVALUAT 1,HFD 101,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B56 EP B56 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800020 ER PT J AU BUTROUS, G LIPICKY, RJ MOORE, EN AF BUTROUS, G LIPICKY, RJ MOORE, EN TI RELATION BETWEEN DOSE AND QT INTERVAL SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. UNIV PENN,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B59 EP B59 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800026 ER PT J AU ESCANDE, D LIPICKY, RJ MOSS, A RODEN, D MOORE, EN AF ESCANDE, D LIPICKY, RJ MOSS, A RODEN, D MOORE, EN TI CAN WE PROLONG REPOLARIZATION WITHOUT TORSADES SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. VANDERBILT UNIV,DIV CLIN PHARMACOL,NASHVILLE,TN 37232. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PREVENT & COMMUNITY MED,HEART RES FOLLOW UP PROGRAM,ROCHESTER,NY 14642. UNIV PENN,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B56 EP B57 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800021 ER PT J AU FRIDAY, K LIPICKY, RJ WOOSLEY, R AF FRIDAY, K LIPICKY, RJ WOOSLEY, R TI SCREENING FOR SAFETY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,DIV CLIN PHARMACOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT MED,DIV CLIN PHARMACOL,WASHINGTON,DC 20007. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B35 EP B35 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800013 ER PT J AU JAILLON, P LIPICKY, RJ BOTSTEIN, P MOSS, A AF JAILLON, P LIPICKY, RJ BOTSTEIN, P MOSS, A TI POSTMARKETING SURVEYS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. US FDA,CTR DRUG EVALUAT & RES,OFF DRUG EVALUAT 1,ROCKVILLE,MD 20857. UNIV ROCHESTER,MED CTR,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PREVENT & COMMUNITY MED,HEART RES FOLLOW UP PROGRAM,ROCHESTER,NY 14642. RP JAILLON, P (reprint author), HOP ST ANTOINE,UNITE PHARMACOL CLIN,184 RUE FBG ST ANTOINE,F-75571 PARIS 12,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B57 EP B58 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800023 ER PT J AU KARKOVSKY, A MORGANROTH, J CAMM, J SAMI, M RODEN LIPICKY, R AF KARKOVSKY, A MORGANROTH, J CAMM, J SAMI, M RODEN LIPICKY, R TI CONSIDERING RISKS AND BENEFITS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. PRESBYTERIAN MED CTR PHILADELPHIA,PHILADELPHIA,PA. VANDERBILT UNIV,DIV CLIN PHARMACOL,NASHVILLE,TN 37232. US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B32 EP B33 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800009 ER PT J AU LIPICKY, RJ AF LIPICKY, RJ TI A VIEWPOINT ON DRUGS THAT PROLONG THE QT(C) INTERVAL SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 1992 ANNUAL MEETING OF THE SYMP ON NEW DRUGS AND DEVICES - QT(C) INTERVAL PROLONGATION : IS IT BENEFICIAL OR HARMFUL CY OCT 29, 1992 CL PHILADELPHIA, PA SP MARION MERRELL DOW AB Insufficient evidence exists to suggest that prolongation of the QT interval corrected for heart rate (QT(c)) is necessarily beneficial. In all but life-threatening situations, QT(c) prolongation resulting from pharmacologic agents must be considered a risk. Because dose-response relations for torsades de pointes cannot be established and because prolongation of the QT(c) interval is thought to precede the development of torsades, it is reasonable to assume that the QT(c) prolongation itself constitutes the marker of risk. An assessment of the relation between the dose of a given drug and its effect on the QT(c) interval will aid in making the judgement that the potential benefit outweighs the risk. Ideally, a drug should demonstrate as wide a safety margin as possible, as reflected in a large separation between the ED50 value associated with therapeutic benefit and that associated with QT(c) prolongation. RP LIPICKY, RJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857, USA. NR 0 TC 20 Z9 21 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B53 EP B54 DI 10.1016/0002-9149(93)90042-B PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800017 PM 8256757 ER PT J AU LIPICKY, RJ MORGANROTH, J GOLDBERG, M AF LIPICKY, RJ MORGANROTH, J GOLDBERG, M TI QT INTERVAL AND TORSADES SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 UNIV PENN,PHILADELPHIA,PA 19104. PRESBYTERIAN MED CTR PHILADELPHIA,PHILADELPHIA,PA. RP LIPICKY, RJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B58 EP B58 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800025 ER PT J AU MOORE, EN LIPICKY, ENR BOTSTEIN, P RODEN, D AF MOORE, EN LIPICKY, ENR BOTSTEIN, P RODEN, D TI TESTING CLASS-III DRUGS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 US FDA,CTR DRUG EVALUAT & RES,OFF DRUG EVALUAT 1,ROCKVILLE,MD 20857. VANDERBILT UNIV,DIV CLIN PHARMACOL,NASHVILLE,TN 37232. US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. RP MOORE, EN (reprint author), UNIV PENN,SUITE 201,3800 SPRUCE ST,PHILADELPHIA,PA 19104, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B55 EP B55 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800019 ER PT J AU MORGANROTH, J RODEN, D LIPICKY, R AF MORGANROTH, J RODEN, D LIPICKY, R TI IS QT(C) INTERVAL PROLONGATION HARMFUL SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 PRESBYTERIAN MED CTR PHILADELPHIA,PHILADELPHIA,PA. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. VANDERBILT UNIV,DIV CLIN PHARMACOL,NASHVILLE,TN 37232. US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B32 EP B32 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800008 ER PT J AU SEDMAN, A MOORE, EN LIPICKY, RJ RODEN, D AF SEDMAN, A MOORE, EN LIPICKY, RJ RODEN, D TI CARDIOACTIVE EFFECTS OF NONCARDIAC DRUGS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 UNIV PENN,PHILADELPHIA,PA 19104. US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. VANDERBILT UNIV,DIV CLIN PHARMACOL,NASHVILLE,TN 37232. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B57 EP B57 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800022 ER PT J AU WENGER, T MOSS, A JAILLON, P WOOSLEY, R LIPICKY, RJ MORGANROTH, J AF WENGER, T MOSS, A JAILLON, P WOOSLEY, R LIPICKY, RJ MORGANROTH, J TI CORRECTING THE QT MEASUREMENT SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 PRESBYTERIAN MED CTR,PHILADELPHIA,PHILADELPHIA,PA. GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,DIV CLIN PHARMACOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT MED,DIV CLIN PHARMACOL,WASHINGTON,DC 20007. HOP ST ANTOINE,UNITE PHARMACOL CLIN,F-75571 PARIS 12,FRANCE. UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. US FDA,CTR DRUG EVALUAT & RES DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B34 EP B35 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800012 ER PT J AU WENGER, T CAMM, J MOSS, A LIPICKY, RJ AF WENGER, T CAMM, J MOSS, A LIPICKY, RJ TI MEASURING QT INTERVALS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Discussion C1 UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PREVENT & COMMUNITY MED,HEARTH RES FOLLOW UP PROGRAM,ROCHESTER,NY 14642. US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 26 PY 1993 VL 72 IS 6 BP B33 EP B34 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LU428 UT WOS:A1993LU42800010 ER PT J AU MALOZOWSKI, S TANNER, LA WYSOWSKI, D FLEMING, GA AF MALOZOWSKI, S TANNER, LA WYSOWSKI, D FLEMING, GA TI GROWTH-HORMONE, INSULIN-LIKE GROWTH FACTOR-I, AND BENIGN INTRACRANIAL HYPERTENSION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID PSEUDOTUMOR CEREBRI RP MALOZOWSKI, S (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 4 TC 99 Z9 100 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 26 PY 1993 VL 329 IS 9 BP 665 EP 666 DI 10.1056/NEJM199308263290917 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LU217 UT WOS:A1993LU21700030 PM 8341354 ER PT J AU TAKAO, M ABRAMIC, M MOOS, M OTRIN, VR WOOTTON, JC MCLENIGAN, M LEVINE, AS PROTIC, M AF TAKAO, M ABRAMIC, M MOOS, M OTRIN, VR WOOTTON, JC MCLENIGAN, M LEVINE, AS PROTIC, M TI A 127 KDA COMPONENT OF A UV-DAMAGED DNA-BINDING COMPLEX, WHICH IS DEFECTIVE IN SOME XERODERMA-PIGMENTOSUM GROUP-E PATIENTS, IS HOMOLOGOUS TO A SLIME-MOLD PROTEIN SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPLEMENTATION GROUP-E; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI; MAMMALIAN-CELLS; EXCISION REPAIR; PRIMATE CELLS; MUTATIONS; ACID; PHOTOPRODUCTS; CLONING AB A cDNA which encodes a approximately 127 kDa UV-damaged DNA-binding (UV-DDB) protein with high affinity for (6-4)pyrimidine dimers [Abramic', M., Levine, A.S. & Protic', M., J. Biol. Chem. 266:22493-22500, 1991] has been isolated from a monkey cell cDNA library. The presence of this protein in complexes bound to UV-damaged DNA was confirmed by immunoblotting. The human cognate of the UV-DDB gene was localized to chromosome 11. UV-DDB mRNA was expressed in all human tissues examined, including cells from two patients with xeroderma pigmentosum (group E) that are deficient in UV-DDB activity, which suggests that the binding defect in these cells may reside in a dysfunctional UV-DDB protein. Database searches have revealed significant homology of the UV-DDB protein sequence with partial sequences of yet uncharacterized proteins from Dictyostelium discoideum (44% identity over 529 amino acids) and Oryza sativa (54% identity over 74 residues). According to our results, the UV-DDB polypeptide belongs to a highly conserved, structurally novel family of proteins that may be involved in the early steps of the UV response, e.g., DNA damage recognition. C1 NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS SECT,BLDG 6,RM 1A-15,BETHESDA,MD 20892. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20209. US FDA,DIV CELLULAR & GENE THERAPY,DEV BIOL LAB,BETHESDA,MD 20892. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 55 TC 87 Z9 89 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 25 PY 1993 VL 21 IS 17 BP 4111 EP 4118 DI 10.1093/nar/21.17.4111 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV915 UT WOS:A1993LV91500027 PM 8371985 ER PT J AU TROXELL, TC AF TROXELL, TC TI IMPACT OF CHEMISTRY ON FOOD SAFETY - THE GOVERNMENT VIEWPOINT 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 AUG 22 PY 1993 VL 206 BP 2 EP CHAL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100987 ER PT J AU SHEININ, EB AF SHEININ, EB TI REVIEW OF RADIOPHARMACEUTICAL INDS AND NDAS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DIV MED IMAGING SURG & DENT DRUG PROD,ROCKVILLE,MD 20857. 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 AUG 22 PY 1993 VL 206 BP 19 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200019 ER PT J AU LEVCHUK, JW AF LEVCHUK, JW TI COMPLIANCE WITH GOOD MANUFACTURING PRACTICE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,STERILE DRUGS BRANCH,ROCKVILLE,MD 20855. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 20 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP322 UT WOS:A1993LP32200020 ER PT J AU WELSH, WJ LIN, W TERSIGNI, S CAREY, S BROWER, J ZIELINSKI, W LAYLOFF, T SPENCER, J PAGE, S AF WELSH, WJ LIN, W TERSIGNI, S CAREY, S BROWER, J ZIELINSKI, W LAYLOFF, T SPENCER, J PAGE, S TI APPLICATION OF NEURAL-NETWORK AND MULTIVARIATE DATA-ANALYSIS APPROACHES ON TRACE HPLC PROFILES FOR DISCRIMINATING AMONG COMMERCIAL MANUFACTURES OF L-TRYPTOPHAN SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV MISSOURI,DEPT CHEM,ST LOUIS,MO 63121. US FDA,DIV DRUG ANAL,ST LOUIS,MO 63101. US FDA,CTR FOOD SAFETY & NUTR,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 35 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32101289 ER PT J AU TAKENAKA, NE MILLER, DW LEE, ME BELAND, FA AF TAKENAKA, NE MILLER, DW LEE, ME BELAND, FA TI STYRENE AND 4-PHENYLCYCLOHEXENE IN LATEX-BACKED CARPET 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 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 AUG 22 PY 1993 VL 206 BP 39 EP ANYL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100377 ER PT J AU LAMPKIN, WT AF LAMPKIN, WT TI FDA CONSIDERATION ON ELECTRONIC IDENTIFICATION SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 42 EP CINF PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100964 ER PT J AU TRUCKSESS, MW STACK, ME AF TRUCKSESS, MW STACK, ME TI IMMUNOAFFINITY COLUMN COUPLED WITH LIQUID-CHROMATOGRAPHY PRECOLUMN DERIVATIZATION FOR DETERMINATION OF FUMONISIN B1 IN CANNED AND FROZEN CORN SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DIV NAT PROD,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 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 AUG 22 PY 1993 VL 206 BP 42 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100042 ER PT J AU BLOCK, E PUTMAN, D THIRUVAZHI, M CALVEY, EM ROACH, JAG AF BLOCK, E PUTMAN, D THIRUVAZHI, M CALVEY, EM ROACH, JAG TI NEW DIRECTIONS IN THE ANALYSIS OF ORGANOSULFUR FLAVORANTS FROM ONION, GARLIC AND OTHER ALLIUM SPECIES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SUNY Albany, DEPT CHEM, ALBANY, NY 12222 USA. US FDA, CTR FOOD SAFETY & APPL NUTR, WASHINGTON, DC 20204 USA. RI Block, Eric/D-3989-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 86 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100086 ER PT J AU ARMSTRONG, DJ RAINEY, NH AF ARMSTRONG, DJ RAINEY, NH TI REDUCED-FAT CHEESE - REGULATIONS AND DEFINITIONS 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. US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 22 PY 1993 VL 206 BP 92 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100092 ER PT J AU ITO, Y SHINOMIYA, K FALES, HM WEISZ, A SCHER, AL AF ITO, Y SHINOMIYA, K FALES, HM WEISZ, A SCHER, AL TI PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY - A NEW PREPARATIVE-SCALE PURIFICATION TECHNIQUE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. NR 0 TC 1 Z9 1 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 AUG 22 PY 1993 VL 206 BP 154 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100154 ER PT J AU SCHER, AL WEISZ, A ITO, Y AF SCHER, AL WEISZ, A ITO, Y TI EQUILIBRIUM-MODEL FOR PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 AUG 22 PY 1993 VL 206 BP 155 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA LP321 UT WOS:A1993LP32100155 ER PT J AU WAGNER, RM WOODS, CW HAYES, JA KOCHANSKY, JP HILL, JC FRASER, BA AF WAGNER, RM WOODS, CW HAYES, JA KOCHANSKY, JP HILL, JC FRASER, BA TI ISOLATION AND IDENTIFICATION OF A NOVEL PEPTIDE FROM THE ACCESSORY SEX GLAND OF THE FEMALE HOUSE-FLY, MUSCA-DOMESTICA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HINDGUT; ACID C1 USDA ARS, BELTSVILLE AGR RES CTR, INST PLANT SCI, INSECT NEUROBIOL & HORMONE LAB, BELTSVILLE, MD 20705 USA. UNIV MARYLAND, DEPT ANIM SCI, COLL PK, MD 20809 USA. US FDA, CTR BIOL EVALUAT & RES, BETHESDA, MD 20892 USA. RP WAGNER, RM (reprint author), USDA ARS, BELTSVILLE AGR RES CTR, INST LIVESTOCK & POULTRY SCI, LIVESTOCK INSECTS LAB, BELTSVILLE, MD 20705 USA. NR 15 TC 11 Z9 11 U1 3 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 16 PY 1993 VL 194 IS 3 BP 1336 EP 1343 DI 10.1006/bbrc.1993.1971 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LT517 UT WOS:A1993LT51700054 PM 8352792 ER PT J AU HALL, RH KHAMBATY, FM KOTHARY, M KEASLER, SP AF HALL, RH KHAMBATY, FM KOTHARY, M KEASLER, SP TI NON-01 VIBRIO-CHOLERAE SO LANCET LA English DT Letter RP HALL, RH (reprint author), US FDA,WASHINGTON,DC 20204, USA. NR 0 TC 42 Z9 44 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD AUG 14 PY 1993 VL 342 IS 8868 BP 430 EP 430 DI 10.1016/0140-6736(93)92839-L PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LR900 UT WOS:A1993LR90000034 PM 8101920 ER PT J AU CHUNG, JH WHITELEY, M FELSENFELD, G AF CHUNG, JH WHITELEY, M FELSENFELD, G TI A 5' ELEMENT OF THE CHICKEN BETA-GLOBIN DOMAIN SERVES AS AN INSULATOR IN HUMAN ERYTHROID-CELLS AND PROTECTS AGAINST POSITION EFFECT IN DROSOPHILA SO CELL LA English DT Article ID LOCUS-CONTROL REGION; DOMINANT CONTROL REGION; TOPOISOMERASE-II SITES; GENE-EXPRESSION; WHITE GENE; HYPERSENSITIVE SITES; ACTIVATION REGION; SENSITIVE DOMAIN; CHROMATIN DOMAIN; TRANSGENIC MICE AB We have characterized an element near the 5' boundary of the chicken beta-globin domain that insulates a reporter gene from the activating effects of a nearby beta-globin locus control region (5'HS2) when assayed in the human erythroid cell line K562. We show that the insulation mechanism is directional, that it operates at the level of transcription, and that it involves the alteration of chromatin structure over the promoter of the gene. The insulator has no significant stimulatory or inhibitory effects of its own. In transgenic Drosophila, the insulator protects the white minigene from position effects. The action of the insulator thus is not restricted to erythroid or mammalian cells, suggesting that such elements may serve an important and widely distributed function in the organization of chromatin structure. C1 US FDA,DIV CELLULAR & GENE THERAPY,BETHESDA,MD 20892. RP CHUNG, JH (reprint author), NIH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 51 TC 687 Z9 699 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 13 PY 1993 VL 74 IS 3 BP 505 EP 514 DI 10.1016/0092-8674(93)80052-G PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LT739 UT WOS:A1993LT73900012 PM 8348617 ER PT J AU POLUSHIN, NN CHEN, BC ANDERSON, LW COHEN, JS AF POLUSHIN, NN CHEN, BC ANDERSON, LW COHEN, JS TI SYNTHESIS AND CHARACTERIZATION OF IMIDAZOYL-LINKED SYNTHONS AND 3'-CONJUGATED THYMIDINE DERIVATIVES SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CLEAVAGE; RIBONUCLEASES; GENERATION; MECHANISM; PEPTIDES AB The synthesis of the phosphoramidites and H-phosphonates of imidazoyl derivatives, including histidine and imidazoleacetic acid, blocked at the imidazole and amino groups and connected by a hexane linker arm, are described. These synthons have been used to synthesize novel 3'-conjugated thymidine derivatives using 5'-(dimethoxytrityl)thymidine. These synthons are being used to prepare oligonucleotides with terminal imidazole groups on the automatic synthesizer. C1 GEORGETOWN UNIV,DEPT PHARMACOL,CANC PHARMACOL SECT,WASHINGTON,DC 20007. US FDA,DIV CLIN PHARMACOL,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20850. NR 18 TC 15 Z9 15 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD AUG 13 PY 1993 VL 58 IS 17 BP 4606 EP 4613 DI 10.1021/jo00069a022 PG 8 WC Chemistry, Organic SC Chemistry GA LW058 UT WOS:A1993LW05800022 ER PT J AU KANTOR, J ABRAMS, S IRVINE, K SNOY, P KAUFMAN, H SCHLOM, J AF KANTOR, J ABRAMS, S IRVINE, K SNOY, P KAUFMAN, H SCHLOM, J TI SPECIFIC IMMUNOTHERAPY USING A RECOMBINANT VACCINIA VIRUS EXPRESSING HUMAN CARCINOEMBRYONIC ANTIGEN SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID GENE C1 US FDA, BETHESDA, MD 20892 USA. RP KANTOR, J (reprint author), NCI, TUMOR IMMUNOL & BIOL LAB, BETHESDA, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 12 PY 1993 VL 690 BP 370 EP 373 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LX021 UT WOS:A1993LX02100047 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI FDA INFORMATION AVAILABLE ON CD-ROM 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 AUG 11 PY 1993 VL 270 IS 6 BP 693 EP 693 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LQ338 UT WOS:A1993LQ33800008 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI REGULATION OF DIETARY-SUPPLEMENTS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA, OFF HLTH AFFAIRS, PARKLAWN BLDG, 5600 FISHERS LN, ROCKVILLE, MD 20857 USA. NR 2 TC 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 AUG 11 PY 1993 VL 270 IS 6 BP 693 EP 693 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LQ338 UT WOS:A1993LQ33800007 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI DEVICE FAST-TRACK PLAN SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA, OFF HLTH AFFAIRS, PARKLAWN BLDG, 5600 FISHERS LN, ROCKVILLE, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 11 PY 1993 VL 270 IS 6 BP 693 EP 693 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LQ338 UT WOS:A1993LQ33800006 ER PT J AU HONGYO, T BUZARD, GS CALVERT, RJ WEGHORST, CM AF HONGYO, T BUZARD, GS CALVERT, RJ WEGHORST, CM TI COLD SSCP - A SIMPLE, RAPID AND NONRADIOACTIVE METHOD FOR OPTIMIZED SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; PCR-SSCP; NONISOTOPIC SSCP; MUTATIONS AB A rapid (< 2.5 hrs) method for single-strand conformation polymorphism (SSCP) analysis of PCR products that allows the use of ethidium bromide staining is described. PCR products ranging in size from 117 to 256 bp were evaluated for point mutations and polymorphisms by 'cold SSCP' in commercially available pre-cast polyacrylamide mini-gels. Several electrophoretic parameters (running temperature, buffers, denaturants, DNA concentration, and gel polyacrylamide concentration) were found to influence the degree of strand separation and appeared to be PCR fragment specific. Use of the 'cold' SSCP technique and the mini-gel format allowed us to readily optimize the electrophoretic conditions for each PCR fragment. This greatly increased our ability to detect polymorphisms compared to conventional, radioisotope-labeled 'hot' SSCP, typically run under two standard temperature conditions. Excellent results have been obtained in resolving mutant PCR fragments from human p53 exons 5 through 8, human HLA-DOA, human K-ras exons 1 and 2, and rat K-ras exon 3. Polymorphisms could be detected when mutant DNA comprised as little as 3% of the total gene copies in a PCR mixture. Compared to standard 'hot' SSCP, this novel non-isotopic method has additional advantages of dramatically increased speed, precise temperature control, reproducibility, and easily and inexpensively obtainable reagents and equipment. This new method also lacks the safety and hazardous waste management concerns associated with radioactive methods. C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. PRI DYN CORP,FCRDC,BCDP,FREDERICK,MD 21702. US FDA,OFF SPECIAL NUTR,LAUREL,MD. NR 21 TC 321 Z9 329 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 11 PY 1993 VL 21 IS 16 BP 3637 EP 3642 DI 10.1093/nar/21.16.3637 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT965 UT WOS:A1993LT96500005 PM 8367279 ER PT J AU UDAYKUMAR EPSTEIN, JS HEWLETT, IK AF UDAYKUMAR EPSTEIN, JS HEWLETT, IK TI A NOVEL METHOD EMPLOYING UNG TO AVOID CARRY-OVER CONTAMINATION IN RNA-PCR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID URACIL-DNA GLYCOSYLASE C1 US FDA,CBER,NLRC,MOLEC VIROL LAB,ROOM 263,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852. NR 5 TC 6 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 11 PY 1993 VL 21 IS 16 BP 3917 EP 3918 DI 10.1093/nar/21.16.3917 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT965 UT WOS:A1993LT96500058 PM 8367319 ER PT J AU SALONPAA, P HAKKOLA, J PASANEN, M PELKONEN, O VAHAKANGAS, K BATTULA, N NOUSO, K RAUNIO, H AF SALONPAA, P HAKKOLA, J PASANEN, M PELKONEN, O VAHAKANGAS, K BATTULA, N NOUSO, K RAUNIO, H TI RETROVIRUS-MEDIATED STABLE EXPRESSION OF HUMAN CYP2A6 IN MAMMALIAN-CELLS SO EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION LA English DT Article DE CYTOCHROME-P4502A6 (HUMAN); HETEROLOGOUS EXPRESSION; CYP2A6 RECOMBINANT EXPRESSION VECTOR; NIH 3T3 CELLS ID HUMAN-LIVER-MICROSOMES; COUMARIN 7-HYDROXYLASE ACTIVITY; METABOLIC-ACTIVATION; CHEMICAL CARCINOGENESIS; HUMAN CYTOCHROME-P450S; INSERTION SIGNAL; MOUSE; AFLATOXIN-B1; ADDUCTS; ENZYME AB To study the pharmacological and toxicological significance of the human cytochrome P450 isoform CYP2A6, we expressed it in mammalian cells by retrovirus-mediated gene transfer. The LXSN vector and PA317 packaging cells were used to create amphotropic recombinant retroviruses containing CYPZA6 cDNA. NIH 3T3 and HeLa cells were infected with these retroviruses and cell clones expressing CYP2A6 were selected. The integration of the CYP2A6 construct was verified by PCR analysis and northern blot analysis showed that a 5 kb mRNA containing the CYP2A6 was present in the cells. The integrated cDNA directed the expression of catalytically active CYP2A6 enzyme which has remained stable over numerous cell passages. No oxidation of several other P450 substrates was detected. The promutagen aflatoxin B1 was metabolized to intermediates binding to the host cell genomic DNA by the 3T3 2A6 cells. These cell lines are thus well suited for the study of the catalytic profile and the biological consequences of promutagen activation by the human CYP2A6 isoform. C1 UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND. UNIV KUOPIO,DEPT PHARMACOL & TOXICOL,SF-70211 KUOPIO,FINLAND. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. US FDA,KENSINGTON,MD 20895. NR 35 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6917 J9 EUR J PHARM-ENVIRON JI Eur. J. Pharmacol.-Environ. Toxicol. Pharmacol. Sect. PD AUG 2 PY 1993 VL 248 IS 2 BP 95 EP 102 DI 10.1016/0926-6917(93)90030-T PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LU126 UT WOS:A1993LU12600001 PM 8223969 ER PT J AU FRICKE, WA LAMB, MA RASTOGI, SC AF FRICKE, WA LAMB, MA RASTOGI, SC TI STANDARDS FOR ASSAY OF VON-WILLEBRAND-FACTOR CONCENTRATES - A COLLABORATIVE STUDY SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID FACTOR-VIII CONCENTRATE; LABORATORY EVALUATION; BLEEDING-TIME; ONE-STAGE; DISEASE; PLASMA; 2-STAGE AB A multilaboratory collaborative study was undertaken to assess the feasibility of using a plasma standard for expressing the results of assays for the von Willebrand factor content of von Willebrand factor concentrates and of factor VIII concentrates. Thirteen laboratories tested six concentrates for von Willebrand factor antigen, ristocetin cofactor activity, and multimer content using the World Health Organization plasma standard for factor VIII/von Willebrand factor, 87/718, as a standard. Only a few assays were invalid because of nonparallelism or nonlinearity. Significant interlaboratory and interassay differences were found for both von Willebrand factor antigen and ristocetin cofactor activity. There was generally good agreement between the laboratories with respect to the multimer content in the preparations. With respect to assay validity, a plasma standard could be suitable for assaying concentrated preparations of von Willebrand factor. RP FRICKE, WA (reprint author), US FDA,CBER,HFM-340,BLDG 29,ROOM 311,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 6 Z9 6 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG 2 PY 1993 VL 70 IS 2 BP 351 EP 356 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LR747 UT WOS:A1993LR74700027 PM 8236147 ER PT J AU COUIG, MP MERKATZ, RB AF COUIG, MP MERKATZ, RB TI MEDWATCH - THE NEW MEDICAL PRODUCTS REPORTING PROGRAM SO AMERICAN JOURNAL OF NURSING LA English DT Article RP COUIG, MP (reprint author), US FDA,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 0002-936X J9 AM J NURS JI Am. J. Nurs. PD AUG PY 1993 VL 93 IS 8 BP 65 EP 68 PG 4 WC Nursing SC Nursing GA LP917 UT WOS:A1993LP91700023 PM 8256839 ER PT J AU NIELSEN, S MULLER, J KNEPPER, MA AF NIELSEN, S MULLER, J KNEPPER, MA TI VASOPRESSIN-INDUCED AND CAMP-INDUCED CHANGES IN ULTRASTRUCTURE OF ISOLATED-PERFUSED INNER MEDULLARY COLLECTING DUCTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ELECTRON MICROSCOPY; COLLECTING DUCT ULTRASTRUCTURE; OSMOTIC WATER PERMEABILITY; COATED PITS; ENDOCYTOSIS ID TOAD URINARY-BLADDER; PAPILLARY SURFACE EPITHELIUM; ADH-INDUCED VACUOLES; WATER PERMEABILITY; ANTIDIURETIC-HORMONE; APICAL MEMBRANE; COATED PITS; RAT-KIDNEY; UREA; ENDOCYTOSIS AB Studies were performed to correlate arginine vasopressin (AVP)-induced changes in epithelial ultrastructure with changes in osmotic water permeability in isolated perfused rat terminal inner medullary collecting ducts (tIMCD). The tubules were perfused in three time periods, i.e., a 40-min basal period, a 40-min period with 0.1 nM AVP in the bath, and a 60-min withdrawal period. In each phase, the osmotic water permeability (P(f)) was measured, and the perfused tubules were fixed for electron microscopy. AVP caused a four- to eightfold increase in P(f) and induced several ultrastructural changes as follows: increased cell height of IMCD cells, expansion of the intercellular spaces, formation of large vacuoles, and increased coated pit density in the apical plasma membrane [from 0.6 +/- 0.2 (n = 6) to 2.9 +/- 0.3 (n = 7) pits/100 mum membrane length]. During AVP withdrawal, P(f) decreased toward the basal value in association with partial reversal of the ultrastructural changes including a decrease in coated pit density to 1.0 +/- 0.2 (n = 4). Stimulation with 8-bromoadenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) (0.1 mM) produced similar changes in P(f). Coated pit density increased to 2.1 +/- 0.4 (n = 4) after CAMP stimulation and after cAMP withdrawal decreased to 1.2 +/- 0.2 (n = 6). In contrast to stimulation with AVP, cAMP stimulation did not result in dilated intercellular spaces or formation of large vacuoles. The only ultrastructural feature that directly correlated with the water permeability was the density of coated pits in the apical membrane. Organelles involved in the endocytic pathway were studied with cationized ferritin or albumin-gold in the luminal perfusate. At the end of 40 min basal perfusion or AVP stimulation, luminal tracer was found almost exclusively in large multivesicular bodies (MVB). Tubules perfused with tracer during AVP withdrawal demonstrated rapid tracer accumulation in small vesicles and small MVB within 3-5 min, a time point corresponding to the rapid phase of P(f) decrease. Later (30-60 min) the label was mainly confined to large MVB. Occasionally during AVP stimulation or withdrawal, small coated vesicles and smooth vesicles with coated extensions were noted to contain tracer. The data demonstrate AVP-mediated coated pit formation and cellular changes and show very rapid internalization of apical membrane after AVP withdrawal. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20892. RP NIELSEN, S (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 38 TC 41 Z9 41 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD AUG PY 1993 VL 265 IS 2 BP F225 EP F238 PN 2 PG 14 WC Physiology SC Physiology GA LW032 UT WOS:A1993LW03200086 PM 8396344 ER PT J AU KASPAR, CW TAMPLIN, ML AF KASPAR, CW TAMPLIN, ML TI EFFECTS OF TEMPERATURE AND SALINITY ON THE SURVIVAL OF VIBRIO-VULNIFICUS IN SEAWATER AND SHELLFISH SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID CRASSOSTREA-VIRGINICA; UNITED-STATES; GULF-COAST; INDICATOR BACTERIA; ESCHERICHIA-COLI; OYSTERS; SHELLSTOCK; SALMONELLA; INFECTIONS; WATERS AB Sterilized seawater was used to assess the effects of temperature and salinity on the survival of Vibrio vulnificus. In the temperature range of 13 to 22-degrees-C, numbers of V. vulnificus increased during the 6-day incubation. Temperatures outside this range reduced the time of V. vulnificus survival in sterile 10-ppt seawater. At these restrictive temperatures, V. vulnificus numbers were reduced by 90% after 6 days of incubation. Incubation between 0.5 and 10.5-degrees-C demonstrated that V. vulnificus survives poorly below 8.5-degrees-C. At salinities between 5 and 25 ppt and at 14-degrees-C, V. vulnificus numbers actually increased or remained unchanged after 6 days of incubation. At salinities of 30, 35, and 38 ppt, numbers of V. vulnificus decreased 58, 88, and 83%, respectively. V. vulnificus could not be recovered from deionized water, indicating lysis. When a rifampin-resistant strain of V. vulnificus was used to inoculate sterilized and unsterilized seawater (20 ppt, 20-degrees-C), numbers increased in sterile seawater but decreased to undetectable levels in 14 days in the unsterilized seawater, indicating that biological factors may play a role in the survival of V. vulnificus in the environment. Since our studies demonstrated sensitivity to low temperatures, the survival of V. vulnificus in naturally contaminated oysters at temperatures of 0, 2, and 4-degrees-C was also determined. Numbers of endogenous V. vulnificus in oyster shellstock increased by more than 100-fold in shellstock stored at 30-degrees-C but were reduced approximately 10- and 100-fold after 14 days at 2 to 4-degrees-C and 0-degrees-C, respectively. We conclude that both biological and physicochemical factors are important to the survival of V. vulnificus in the environment and that temperature is critical to controlling its growth in oyster shellstock. C1 US FDA,GULF COAST RES LAB,DAUPHIN ISL,AL 36528. NR 31 TC 202 Z9 207 U1 3 U2 23 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 1993 VL 59 IS 8 BP 2425 EP 2429 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA LP835 UT WOS:A1993LP83500013 PM 8368832 ER PT J AU STOCKBRIDGE, LL AF STOCKBRIDGE, LL TI ELECTROPORATION OF EXCISED MEMBRANE PATCHES FROM NEUROBLASTOMA-CELLS - DEMONSTRATION OF SINGLE PORES SO BIOELECTROCHEMISTRY AND BIOENERGETICS LA English DT Article ID ELECTRICAL BREAKDOWN; LIPID-MEMBRANES; CLAMP AB Excised membrane patches from mouse and human neuroblastoma cells were subjected to positive and negative voltage ramps, from 0.25 mV s-1 to 3.3 mV s-1, using standard patch-clamp techniques. At a critical voltage, Vm(r), the membrane ruptured. Vm(r) ranged from 54 mV to 426 mV with great variability, human cell membranes tending to be more resistant to rupture than mouse cell membranes. The presence or absence of voltage-gated ion channels did not affect the Vm(r). Vm(r) was time and voltage dependent, characteristically resembling electroporation as it is described in the literature. Furthermore, close examination of current traces revealed evidence of the pores themselves, appearing when rupture was imminent. This allowed direct measurement of pore conductances, as well as direct observation of their behavior. C1 US FDA,CTR DEVICES & RADIOL HLTH,ELECTROPHYS BRANCH,ROCKVILLE,MD 20852. NR 20 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0302-4598 J9 BIOELECTROCH BIOENER JI Bioelectrochem. Bioenerg. PD AUG PY 1993 VL 31 IS 3 BP 259 EP 269 DI 10.1016/0302-4598(93)86112-E PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LQ301 UT WOS:A1993LQ30100002 ER PT J AU RAGNI, MV NDIMBIE, OK RICE, EO BONTEMPO, FA NEDJAR, S AF RAGNI, MV NDIMBIE, OK RICE, EO BONTEMPO, FA NEDJAR, S TI THE PRESENCE OF HEPATITIS-C VIRUS (HCV) ANTIBODY IN HUMAN IMMUNODEFICIENCY VIRUS-POSITIVE HEMOPHILIC MEN UNDERGOING HCV SEROREVERSION SO BLOOD LA English DT Article ID NON-B-HEPATITIS; LIVER-DISEASE; NON-A; HIV; PREVALENCE; INFECTION; ASSAY; RISK; AIDS C1 US FDA,CTR BIOL EVALUAT & RES,HEPATITIS LAB,BETHESDA,MD 20205. RP RAGNI, MV (reprint author), UNIV PITTSBURGH,SCH MED,HEMOPHILIA CTR WESTERN PENNS,CENT BLOOD BANK,DEPT MED & PATHOL,PITTSBURGH,PA 15219, USA. NR 21 TC 62 Z9 61 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 AUG 1 PY 1993 VL 82 IS 3 BP 1010 EP 1015 PG 6 WC Hematology SC Hematology GA LQ741 UT WOS:A1993LQ74100046 PM 7687887 ER PT J AU BELL, DA TAYLOR, JA BUTLER, MA STEPHENS, EA WIEST, J BRUBAKER, LH KADLUBAR, FF LUCIER, GW AF BELL, DA TAYLOR, JA BUTLER, MA STEPHENS, EA WIEST, J BRUBAKER, LH KADLUBAR, FF LUCIER, GW TI GENOTYPE-PHENOTYPE DISCORDANCE FOR HUMAN ARYLAMINE N-ACETYLTRANSFERASE (NAT2) REVEALS A NEW SLOW-ACETYLATOR ALLELE COMMON IN AFRICAN-AMERICANS SO CARCINOGENESIS LA English DT Note ID BLADDER-CANCER; CATALYTIC MECHANISM; CARCINOGENESIS; INVOLVEMENT AB Carcinogenic arylamines are acetylated by the hepatic N-acetyltransferase. This enzyme is polymorphic in humans and in some epidemiological studies, the slow-acetylator phenotype has been associated with higher risk of bladder cancer and tower risk of colorectal cancer. The presence of two germline copies of any of several mutant alleles of the NAT2 gene produces a slow-acetylation phenotype. We used a PCR-RFLP technique to identify three known slow-acetylator alleles (M1, M2 and M3). Comparison of results from PCR-RFLP genotyping with caffeine metabolism phenotyping in 42 individuals suggested that an additional slow-acetylator allele was present in our sampled population. We sequenced the NAT2 gene for several discordant slow-acetylator individuals and found a G > A base-change in codon 64 that caused a Arg > Glu amino acid substitution. This sequence change, termed the 'M4' allele, was found in all of the discordant individuals in our population and apparently causes a slow-acetylation phenotype. In addition, we have determined that NAT2 allele frequencies in 372 Caucasian-Americans (WT = 0.25, M1 = 0.45, M2 = 0.28, M3 = 0.02, and M4 = 0.00) and in 128 African-Americans (WT = 0.36, M1 = 0.30, M2 = 0.22, M3 = 0.02 and M4 = 0.09) are significantly different (P < 0.0001). The M4 allele was not found in 372 unrelated Caucasians and appears to be of African origin. C1 NIEHS,BIOCHEM RISK ANAL LAB,C3-03,POB 12333,RES TRIANGLE PK,NC 27709. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. MED COLL GEORGIA,AUGUSTA,GA 30912. NATL CTR TOXICOL RES,JEFFERSON,AR. OI taylor, jack/0000-0001-5303-6398 NR 23 TC 312 Z9 316 U1 1 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1993 VL 14 IS 8 BP 1689 EP 1692 DI 10.1093/carcin/14.8.1689 PG 4 WC Oncology SC Oncology GA LT119 UT WOS:A1993LT11900033 PM 8102597 ER PT J AU THORSHEIM, HR ARMSTRONG, DJ AF THORSHEIM, HR ARMSTRONG, DJ TI RECYCLED PLASTICS FOR FOOD-PACKAGING SO CHEMTECH LA English DT Article RP THORSHEIM, HR (reprint author), US FDA,INDIRECT ADDIT BRANCH,HFS-216,200 C ST SW,WASHINGTON,DC 20204, USA. NR 3 TC 8 Z9 8 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0009-2703 J9 CHEMTECH JI Chemtech PD AUG PY 1993 VL 23 IS 8 BP 55 EP 58 PG 4 WC Chemistry, Applied SC Chemistry GA LU779 UT WOS:A1993LU77900015 ER PT J AU MACKALL, JC BAI, GH ROUSE, DA ARMOA, GRG CHUIDIAN, F NAIR, J MORRIS, SL AF MACKALL, JC BAI, GH ROUSE, DA ARMOA, GRG CHUIDIAN, F NAIR, J MORRIS, SL TI A COMPARISON OF THE T-CELL DELAYED-TYPE HYPERSENSITIVITY EPITOPES OF THE 19-KD ANTIGENS FROM MYCOBACTERIUM-TUBERCULOSIS AND MYCO-INTRACELLULARE USING OVERLAPPING SYNTHETIC PEPTIDES SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE MYCOBACTERIAL PEPTIDES; MYCOBACTERIUM-TUBERCULOSIS; MYCOBACTERIUM-INTRACELLULARE; DELAYED-TYPE HYPERSENSITIVITY ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MULTIDRUG-RESISTANT TUBERCULOSIS; SEQUENCE-ANALYSIS; VIRUS INFECTION; PROTEIN; LEPRAE; STIMULATION; RESPONSES; OUTBREAK AB Mycobacterial disease remains a serious international public health concern. Improved methods to rapidly and specifically detect mycobacterial infections would greatly enhance clinical management of these diseases. To define species-specific T cell epitopes that may be useful for the immunodiagnosis of mycobacterial infections, polymerized synthetic peptides from the 19-kD Mycobacterium tuberculosis and Myco. intracellulare protein homologues were tested in guinea pig DTH assays. Five Myco. tuberculosis and eight Myco. intracellulare peptides evoked skin test responses. Although all of the active Myco. tuberculosis and seven of the Myco. intracellulare peptides elicited non-specific DTH reactions, the peptide IN13 induced a Myco. intracellulare-specific skin test reaction, and thus represents a specific Myco. intracellulare T cell DTH epitope. This result suggests that the development of monospecific peptide-based immunodiagnostic reagents may be feasible for future clinical use. C1 US FDA,CTR BIOL EVALUAT & RES,MYCOBACTERIA LAB,BLDG 29,ROOM 420,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852. KOREAN NATL TB ASSOC,KOREAN INST TB,SEOUL,SOUTH KOREA. OSWALDO CRUZ FDN,NATL INST QUAL CONTROL HLTH,RIO JANEIRO,BRAZIL. NR 31 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD AUG PY 1993 VL 93 IS 2 BP 172 EP 177 PG 6 WC Immunology SC Immunology GA LP575 UT WOS:A1993LP57500007 PM 7688674 ER PT J AU DIMITROV, DS FRANZOSO, G SALMAN, M BLUMENTHAL, R TARSHIS, M BARILE, MF ROTTEM, S AF DIMITROV, DS FRANZOSO, G SALMAN, M BLUMENTHAL, R TARSHIS, M BARILE, MF ROTTEM, S TI MYCOPLASMA-FERMENTANS (INCOGNITUS STRAIN) CELLS ARE ABLE TO FUSE WITH T-LYMPHOCYTES SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON THE CHANGING ROLE OF MYCOPLASMAS IN RESPIRATORY DISEASE AND AIDS CY NOV 30-DEC 05, 1991 CL SCOTTSDALE, AZ ID INFECTIVITY; INHIBITION; VESICLES; BINDING; VIRUSES; FUSION; AIDS AB Characteristics of the fusion of Mycoplasma fermentans (incognitus strain) with cultured lymphocytes were investigated. The rate and extent of fusion were monitored continuously in an assay that measured lipid mixing on the basis of dequenching of a fluorescent probe, octadecylrhodamine (R18), incorporated into mycoplasmas. Fusion of M. fermentans was detected with CD4+ (Molt-3) cells, CD4- (12E1) cells, and primary peripheral-blood lymphocytes. The level of fusion was relatively low (8%-12%). Detection of a similarly low level of fusion by fluorescence microscopy suggested the involvement of a specific lymphocyte subpopulation. After a short lag period, fusion at 37-degrees-C proceeded exponentially for approximately 30 minutes and was virtually complete at 60 minutes. Throughout the process, lymphocytes remained intact. Fusion was stimulated by CaCl2 but not by MgCl2; its inhibition by antisera to M. fermentans and by pretreatment of M. fermentans with proteolytic enzymes implied that the mycoplasmas possessed a proteinase-sensitive receptor involved in fusion. Mycoplasmas were rendered nonfusogenic by treatment with the uncoupler CCCP (carbonyl cyanide m-chlorophenylhydrazone; 5 muM) but were unaffected by treatment with chlorpromazine (10 muM) or DCCD (dicyclohexylcarbodiimide; 50 muM); these findings suggested that a proton gradient across the cell membrane is required for fusion. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MEMBRANE & ULTRASTRUCT RES,POB 1172,IL-91010 JERUSALEM,ISRAEL. NCI,MATH BIOL LAB,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,MYCOPLASMA LAB,BETHESDA,MD 20014. NR 19 TC 11 Z9 11 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1993 VL 17 SU 1 BP S305 EP S308 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LQ130 UT WOS:A1993LQ13000051 PM 8399933 ER PT J AU BARRON, MG PLAKAS, SM WILGA, PC BALL, T AF BARRON, MG PLAKAS, SM WILGA, PC BALL, T TI ABSORPTION, TISSUE DISTRIBUTION AND METABOLISM OF CHLORPYRIFOS IN CHANNEL CATFISH FOLLOWING WATERBORNE EXPOSURE SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE KINETICS; PESTICIDE; BIOTRANSFORMATION; BIOACCUMULATION ID ICTALURUS-PUNCTATUS; PHARMACOKINETICS; BIOCONCENTRATION; DISPOSITION; EXCRETION; PARATHION AB The pharmacokinetics, tissue distribution, and metabolism of waterborne chlorpyrifos were investigated in channel catfish (Ictalurus punctatus) fitted with arterial and urinary catheters. Pharmacokinetic analysis indicated rapid absorption of parent chlorpyrifos from water into blood and slower distribution to peripheral tissues. Total C-14 residue concentrations were highest in fat and lowest in muscle. Parent chlorpyrifos comprised >90% of the total C-14 residues in the whole fish. C-14 residues were excreted by renal and biliary routes as metabolites of chlorpyrifos; excretion of the parent chemical was negligible. Trichloropyridinol (TCP) was the major metabolite in blood (approximately 40% of total residues), whereas the glucuronide conjugate of TCP was the major metabolite in urine (60-90%) and bile (>90%). The pharmacokinetics and metabolism of waterborne chlorpyrifos in the channel catfish were similar to the disposition of chlorpyrifos in other vertebrates. C1 US FDA, DIV SEAFOOD RES, DAUPHIN ISL, AL 36528 USA. DOW CHEM CO USA, MIDLAND, MI 48674 USA. RP BARRON, MG (reprint author), ENVIRONM SCI & ENGN INC, POB 1703, GAINESVILLE, FL 32602 USA. NR 26 TC 19 Z9 20 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-7268 EI 1552-8618 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD AUG PY 1993 VL 12 IS 8 BP 1469 EP 1476 DI 10.1897/1552-8618(1993)12[1469:ATDAMO]2.0.CO;2 PG 8 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA LP260 UT WOS:A1993LP26000014 ER PT J AU HONIG, PK WORTHAM, DC ZAMANI, K CONNER, DP MULLIN, JC CANTILENA, LR AF HONIG, PK WORTHAM, DC ZAMANI, K CONNER, DP MULLIN, JC CANTILENA, LR TI EFFECT OF CONCOMITANT ADMINISTRATION OF CIMETIDINE AND RANITIDINE ON THE PHARMACOKINETICS AND ELECTROCARDIOGRAPHIC EFFECTS OF TERFENADINE SO EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE TERFENADINE METABOLISM; CIMETIDINE; RANITIDINE; ANTIHISTAMINES; TORSADES-DE-POINTES; PHARMACOKINETICS; DRUG INTERACTION ID DRUG-INTERACTIONS; ERYTHROMYCIN AB Terfenadine is a widely prescribed non-sedating antihistamine which undergoes rapid and almost complete first pass biotransformation to an active carboxylic acid metabolite. It is unusual to find unmetabolised terfenadine in the plasma of patients taking the drug. Terfenadine in vitro is a potent blocker of the myocardial potassium channel. Overdose, hepatic compromise and the coadministration of ketoconazole and erythromycin result in the accumulation of terfenadine, which is thought to be responsible of QT prolongation and Torsades de Pointes ventricular arrhythmia in susceptible individuals. Cimetidine and ranitidine are two popular H-2 antagonists which are often taken with terfenadine. The effects of cimetidine and ranitidine on terfenadine metabolism were studied in two cohorts of 6 normal volunteers given the recommended dose of terfenadine (60 mg every 12 h) for 1 week prior to initiation of cimetidine 600 mg every 12 h or ranitidine 150 mg every 12 h. Pharmacokinetic profiles and morning pre-dose electrocardiograms were obtained whilst the patients were on terfenadine alone and after the addition of cimetidine or rantidine. One of the subjects in each cohort had a detectable plasma level of parent compound after 1 week of terfenadine therapy alone; it did not accumulate further after addition of the H-2 antagonist. The pharmacokinetics of the carboxylic acid metabolite of terfenadine (C(max), t(max), AUC) were not significantly changed after co-administration of either H-2 antagonist. None of the remaining 5 subjects in either cohort demonstrated accumulation of unmetabolised terfenadine after addition of the respective H-2 antagonist and electrocardiographic QT intervals and T-U morphology in them was not changed during the course of the study. We conclude that cimetidine and ranitidine in the dosages used in this study did not affect the metabolism of terfenadine, and that patients exposed to these drug combinations are not at increased risk of altered cardiac repolarisation. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,DIV CLIN PHARMACOL,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,DEPT CARDIOL,WASHINGTON,DC 20307. US FDA,ROCKVILLE,MD 20857. RI Zamani, Kaveh/A-9182-2011 NR 28 TC 24 Z9 25 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6970 J9 EUR J CLIN PHARMACOL JI Eur. J. Clin. Pharmacol. PD AUG PY 1993 VL 45 IS 1 BP 41 EP 46 DI 10.1007/BF00315348 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LR694 UT WOS:A1993LR69400007 PM 8405028 ER PT J AU KLINMAN, DM HOLMES, KL CONOVER, J CHIANG, BL GERSHWIN, ME AF KLINMAN, DM HOLMES, KL CONOVER, J CHIANG, BL GERSHWIN, ME TI B-1A AND CONVENTIONAL B-CELLS FROM AUTOIMMUNE NZB.H-2BM12 MICE EXHIBIT SIMILAR FUNCTIONAL-CHARACTERISTICS IN-VIVO SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE B-1 CELLS; LY-1 CELLS; IMMUNOGLOBULIN ISOTYPE; AUTOIMMUNITY; LUPUS ID SYSTEMIC LUPUS-ERYTHEMATOSUS; T-HELPER CELLS; LY-1 B; ANTIBODY-PRODUCTION; RHEUMATOID-FACTOR; VIABLE MOTHEATEN; CROSS-REACTIVITY; MURINE MODELS; CD5+; AUTOANTIBODIES AB NZB.H-2bm12 mice develop an autoimmune syndrome characterized by the overproduction of anti-DNA antibodies and the expansion of B-1B cells. Thus, these animals provide a useful model to examine the antigenic specificity, cross-reactivity and functional capability of B-1 versus conventional lymphocytes. Neither the repertoire expressed by in vivo activated Ly-1+ splenic lymphocytes, nor their cross-reactivity, differed significantly from that of conventional splenic B cells. When Ly-1+ cells were cultured in vitro in the presence of lipopolysaccharide plus interleukin-4 or interferon gamma, they underwent isotype switching at the same frequency as conventional B cells. Of interest, B-1 cells from the peritoneal cavity were significantly less likely to undergo isotype switching than those from the spleen. These findings indicate that in vivo activated B-1a and conventional B cells from mice with lupus manifest similar functional characteristics. C1 CBER,FDA,DIV VIROL,FLOW CYTOMETRY SECT,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. UNIV CALIF DAVIS,DIV RHEUMATOL ALLERGY,DAVIS,CA 95616. RP KLINMAN, DM (reprint author), CBER,FDA,RETROVIRAL IMMUNOL SECT,BLDG 29A,RM 3 D10,BETHESDA,MD 20892, USA. OI CHIANG, BOR-LUEN/0000-0002-6705-0286 FU NCI NIH HHS [CA 20816] NR 46 TC 7 Z9 7 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 AUG PY 1993 VL 23 IS 8 BP 1866 EP 1871 DI 10.1002/eji.1830230820 PG 6 WC Immunology SC Immunology GA LT241 UT WOS:A1993LT24100019 PM 7688308 ER PT J AU IWAI, Y PLUZNIK, DH COHEN, RB AF IWAI, Y PLUZNIK, DH COHEN, RB TI SIGNAL-TRANSDUCTION PATHWAYS INVOLVED IN THE INDUCTION OF GM-CSF MESSENGER-RNA IN MURINE T-CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 US FDA,CBER,DIV CYTOKINE BIOL,BETHESDA,MD 20014. KOKURA MEM HOSP,DEPT PEDIAT,KITAKYUSHU,FUKUOKA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1145 EP 1145 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300496 ER PT J AU TOYOKUNI, S SAGRIPANTI, JL AF TOYOKUNI, S SAGRIPANTI, JL TI INDUCTION OF OXIDATIVE SINGLE-STRAND AND DOUBLE-STRAND BREAKS IN DNA BY FERRIC CITRATE SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE HEMOCHROMATOSIS; IRON; DNA DAMAGE; DNA STRAND BREAKS; CITRATE; CARCINOGENS; HYDROGEN PEROXIDE; SUPEROXIDE; FREE RADICALS ID SUPEROXIDE-DEPENDENT FORMATION; RENAL-CELL CARCINOMA; BODY IRON STORES; HYDROXYL RADICALS; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; IDIOPATHIC HEMOCHROMATOSIS; SERUM TRANSFERRIN; OXYGEN RADICALS; ASCORBIC-ACID AB The relative risk of primary hepatocellular carcinoma in genetic hemochromatosis (GH) is estimated at over 200 times as that of control populations. Recently, ferric ion chelated to citrate (Fe-citrate) was identified as the major non-transferrin-bound iron in the serum of GH patients. We investigated whether low concentration of Fe-citrate plus reductant could damage supercoiled plasmid DNA under physiological pH and ionic strength. Incubation of Fe-citrate with either H2O2, L-ascorbate, or L-cysteine induced single- and double-strand breaks in supercoiled plasmid pZ189 in a concentration- and time-dependent fashion. DNA strand breaks produced by Fe-citrate plus H2O2 increased at reduced pH (less-than-or-equal-to 6.9). Catalase and free radical scavengers inhibited the DNA breakage produced by Fe-citrate in combination with each reductant, suggesting that H2O2 and finally .OH are responsible DNA damaging species. The catalytic ability of Fe-citrate to induce DNA strand breaks, particularly double-strand breaks (DSBs), may contribute to the carcinogenic processes observed in GH. C1 US FDA, CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL, DIV LIFE SCI,MOLEC BIOL BRANCH, ROCKVILLE, MD 20857 USA. RI Toyokuni, Shinya/C-1358-2010 OI Toyokuni, Shinya/0000-0002-5757-1109 NR 56 TC 37 Z9 37 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. PD AUG PY 1993 VL 15 IS 2 BP 117 EP 123 DI 10.1016/0891-5849(93)90050-5 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA LP109 UT WOS:A1993LP10900001 PM 8397139 ER PT J AU FEUERS, RJ PATTILLO, FM OSBORN, CK ADAMS, KL DELUCA, D SMITH, WG AF FEUERS, RJ PATTILLO, FM OSBORN, CK ADAMS, KL DELUCA, D SMITH, WG TI APPLICATION OF AN INTEGRATED RATE-EQUATION TO THE INACTIVATION OF CATALASE SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Note DE CATALASE; INTEGRATED RATE EQUATION; KINETICS; ENZYME INACTIVATION; FREE RADICALS ID 3-AMINO-1,2,4-TRIAZOLE; NADPH AB A feature of catalase that has received scant attention in recent years and that may have physiological significance is the peroxide-dependent inactivation of the enzyme. In this article we show how to obtain the second-order rate constant for the inactivation reaction by fitting the reaction progress curve to an integrated rate equation. This method will simplify quantitation of the inactivation and reactivation of catalase. These measurements in tissues with altered metabolic states may reveal new information about the role of catalase in nutrition, aging, and pathology. C1 UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,SLOT S16,4301 W MARKHAM,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. FU NIGMS NIH HHS [5R01 GM 40744] NR 15 TC 12 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG PY 1993 VL 15 IS 2 BP 223 EP 226 DI 10.1016/0891-5849(93)90063-Z PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA LP109 UT WOS:A1993LP10900014 PM 8375696 ER PT J AU TSAI, CM GU, XX BYRD, A AF TSAI, CM GU, XX BYRD, A TI QUANTITATION OF POLYSACCHARIDE IN HAEMOPHILUS TYPE-B CONJUGATE VACCINES BY HIGH-PERFORMANCE ANION-EXCHANGE CHROMATOGRAPHY WITH PULSED AMPEROMETRIC DETECTION SO GLYCOCONJUGATE JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,OFF VACCINES RES,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,OFF REVIEW,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD AUG PY 1993 VL 10 IS 4 BP 319 EP 320 DI 10.1007/BF01210112 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LY104 UT WOS:A1993LY10400311 ER PT J AU ERNEY, DR POOLE, CF AF ERNEY, DR POOLE, CF TI A STUDY OF SINGLE COMPOUND ADDITIVES TO MINIMIZE THE MATRIX INDUCED CHROMATOGRAPHIC RESPONSE ENHANCEMENT OBSERVED IN THE GAS-CHROMATOGRAPHY OF PESTICIDE-RESIDUES SO HRC-JOURNAL OF HIGH RESOLUTION CHROMATOGRAPHY LA English DT Note DE GAS CHROMATOGRAPHY; VAPORIZING INJECTORS; MATRIX EFFECTS; ORGANOPHOSPHORUS PESTICIDE RESIDUES ID SOLVATION MODELS; ENERGY C1 WAYNE STATE UNIV,DEPT CHEM,DETROIT,MI 48202. RP ERNEY, DR (reprint author), US FDA,PESTICIDE & IND CHEM RES CTR,1560 E JEFFERSON AVE,DETROIT,MI 48207, USA. NR 7 TC 51 Z9 53 U1 0 U2 4 PU DR ALFRED HUTHIG VERLAG GMBH PI HEIDELBERG 1 PA POSTFACH 102869, W-69018 HEIDELBERG 1, GERMANY SN 0935-6304 J9 HRC-J HIGH RES CHROM JI HRC-J. High Resolut. Chromatogr. PD AUG PY 1993 VL 16 IS 8 BP 501 EP 503 PG 3 WC Chemistry, Analytical SC Chemistry GA MK701 UT WOS:A1993MK70100011 ER PT J AU HAYES, MP ZOON, KC AF HAYES, MP ZOON, KC TI PRIMING OF HUMAN MONOCYTES FOR ENHANCED LIPOPOLYSACCHARIDE RESPONSES - EXPRESSION OF ALPHA-INTERFERON, INTERFERON REGULATORY FACTORS, AND TUMOR-NECROSIS-FACTOR SO INFECTION AND IMMUNITY LA English DT Article ID TRANSCRIPTION FACTOR; DIFFERENTIAL REGULATION; IFN-ALPHA; GENES; INDUCTION; CELLS; MACROPHAGES; ENDOTOXIN; IRF-1; SEQUENCE AB Culture of human monocytes with either granulocyte-macrophage colony-stimulating factor or gamma interferon (EFN-gamma) results in a primed state, during which these cells express heightened responses to bacterial lipopolysaccharide (LPS). The production of IFN-alpha in response to LPS by human monocytes has an absolute requirement for priming. Tumor necrosis factor (TNF) expression is also greatly enhanced in primed monocytes after LPS stimulation, but unlike IFN-alpha, TNF is readily expressed in unprimed monocytes as well. In an effort to determine the molecular events associated with IFN-alpha induction in this system, freshly isolated human monocytes were primed by culture with either IFN-gamma or granulocyte-macrophage colony-stimulating factor and then treated with LPS; expression of IFN-alpha subtype 2 (IFN-alpha2), IFN regulatory factors (IRFs), and TNF was assessed by Northern (RNA blot) analysis. IRF-1 mRNA is expressed at high levels in monocytes and is regulated by both LPS and priming cytokines, but its expression alone does not correlate with the induction of IFN-alpha2 expression. IRF-2 mRNA is expressed in a more gradual manner following LPS stimulation, implying a possible feedback mechanism for inhibiting IFN-alpha expression. However, nuclear run-on analysis indicates that EFN-alpha2 is not transcriptionally modulated in this system, in striking contrast to TNF, which is clearly regulated at the transcriptional level. In addition, IFN-alpha2 mRNA accumulation is superinduced when primed monocytes are treated with LPS plus cycloheximide, while TNF mRNA is relatively unaffected. The results demonstrate that priming can affect subsequent LPS-induced gene expression at different levels in human monocytes. RP HAYES, MP (reprint author), US FDA,DIV CYTOKINE BIOL,BLDG 29-A,ROOM 2D20,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 32 TC 52 Z9 52 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1993 VL 61 IS 8 BP 3222 EP 3227 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LP357 UT WOS:A1993LP35700017 PM 8335353 ER PT J AU PASCOPELLA, L COLLINS, FM MARTIN, JM JACOBS, WR BLOOM, BR AF PASCOPELLA, L COLLINS, FM MARTIN, JM JACOBS, WR BLOOM, BR TI IDENTIFICATION OF A GENOMIC FRAGMENT OF MYCOBACTERIUM-TUBERCULOSIS RESPONSIBLE FOR IN-VIVO GROWTH ADVANTAGE SO INFECTIOUS AGENTS AND DISEASE-REVIEWS ISSUES AND COMMENTARY LA English DT Article; Proceedings Paper CT 1st Bristol-Myers Squibb Symposium on Infectious Disease Research: The Cell and Molecular Biology of Bacterial-Host Cell Interactions CY FEB 22-23, 1993 CL MONTEREY, CA SP BRISTOL MYERS SQUIBB C1 ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,HOWARD HUGHES MED INST,RES LABS,BRONX,NY 10461. ROCKY MT LABS,HAMILTON,MT. US FDA,MYCOBACTERIA LAB,BETHESDA,MD. NR 10 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1056-2044 J9 INFECT AGENT DIS JI Infect. Agents Dis.-Rev. Issues Comment. PD AUG PY 1993 VL 2 IS 4 BP 282 EP 284 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MZ255 UT WOS:A1993MZ25500027 PM 8173811 ER PT J AU KITADAI, Y YASUI, W YOKOZAKI, H KUNIYASU, H AYHAN, A HARUMA, K KAJIYAMA, G JOHNSON, GR TAHARA, E AF KITADAI, Y YASUI, W YOKOZAKI, H KUNIYASU, H AYHAN, A HARUMA, K KAJIYAMA, G JOHNSON, GR TAHARA, E TI EXPRESSION OF AMPHIREGULIN, A NOVEL GENE OF THE EPIDERMAL GROWTH-FACTOR FAMILY, IN HUMAN GASTRIC CARCINOMAS SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE AMPHIREGULIN; GASTRIC CARCINOMA; GROWTH FACTOR ID HUMAN GASTROINTESTINAL CARCINOMAS; CELL-LINE TMK-1; FACTOR-RECEPTOR; NUCLEAR-LOCALIZATION; COLORECTAL TUMORS; AUTOCRINE GROWTH; FACTOR-ALPHA; EGF; AMPLIFICATION; ONCOGENES AB The expression of mRNA for amphiregulin (AR), a novel gene of the epidermal growth factor family, was examined in 8 human gastric carcinoma cell lines and 32 gastric carcinoma tissues as well as corresponding normal mucosa. Of the 8 gastric carcinoma cell lines, 7 expressed 1.4 kb AR mRNA at various levels. The expression of AR mRNA by TMK-1 and MKN-28 cells was increased by treatment with epidermal growth factor or transforming growth factor alpha. In surgical cases, all the gastric carcinoma tissues and their adjacent normal mucosa expressed AR mRNA. Interestingly, 20 (62.5%) out of 32 tumors expressed AR mRNA at higher levels than their corresponding normal mucosas (tumor/normal greater-than-or-equal-to 1.2). No obvious correlation was observed between the AR mRNA levels and the histological types or tumor staging of gastric carcinoma. Immunohistochemically, AR protein was localized to the cytoplasm and/or nucleus in tumor cells. These results suggest that AR produced by tumor cells may be involved in the pathogenesis and/or progression of human gastric carcinoma. C1 HIROSHIMA UNIV,SCH MED,DEPT PATHOL 1,1-2-3 KASUMI,MINAMI KU,HIROSHIMA 734,JAPAN. HIROSHIMA UNIV,DEPT INTERNAL MED 1,MINAMI KU,HIROSHIMA 734,JAPAN. US FDA,DIV CYTOKINE BIOL,CELL BIOL LAB,BETHESDA,MD 20892. RI AYHAN, Ayse/H-3331-2012; OI AYHAN, Ayse/0000-0003-0136-4271; Yokozaki, Hiroshi/0000-0001-5276-3331 NR 29 TC 41 Z9 41 U1 1 U2 3 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD AUG PY 1993 VL 84 IS 8 BP 879 EP 884 PG 6 WC Oncology SC Oncology GA LU656 UT WOS:A1993LU65600012 PM 8407551 ER PT J AU CALVO, MS GUNDBERG, CM AF CALVO, MS GUNDBERG, CM TI ACUTE CALCITONIN ADMINISTRATION LOWERS CIRCULATING OSTEOCALCIN LEVELS IN RATS THROUGH ENHANCED RENAL CLEARANCE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S204 EP S204 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500349 ER PT J AU KAUP, SM HIGHT, SC AHN, SM RADER, JI AF KAUP, SM HIGHT, SC AHN, SM RADER, JI TI GENDER DIFFERENCES IN BONE MINERALIZATION AMONG RATS FED FLAXSEED SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 US FDA,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S275 EP S275 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500632 ER PT J AU LOOKER, AC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP JOHNSTON, CC LINDSAY, RL AF LOOKER, AC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP JOHNSTON, CC LINDSAY, RL TI FEMORAL BONE-DENSITY OF UNITED-STATES ADULTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NCHS,HYATTSVILLE,MD 20782. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. US FDA,WASHINGTON,DC 20204. INDIANA UNIV,INDIANAPOLIS,IN 46223. NIA,BETHESDA,MD 20816. NIAMS,BETHESDA,MD 20892. HELEN HAYES HOSP,W HAVERSTRAW,NY 10993. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S336 EP S336 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500876 ER PT J AU CONNER, DP ZAMANI, K ALMIREZ, RG MILLORA, E NIX, D SHAH, VP AF CONNER, DP ZAMANI, K ALMIREZ, RG MILLORA, E NIX, D SHAH, VP TI USE OF REFLECTANCE SPECTROPHOTOMETRY IN THE HUMAN CORTICOSTEROID SKIN BLANCHING ASSAY SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID VASOCONSTRICTOR ASSAY; QUANTIFICATION; INFLAMMATION; EFFICACY AB A reflectance spectrophotometric method for evaluation of the skin blanching response to topical corticosteroids was evaluated. This blanching response is used, for drug development and regulatory purposes, to assess potency and bioequivalence of topical corticosteroid products. The common method involves the use of a human rater to measure blanching response in the skin. This study evaluated an instrumental alternative to the human rater and used this method to measure the differences between a number of brand name and generic topical corticosteroid products (six creams and six ointments). Products were applied to the forearms of normal volunteers and the blanching responses were assessed after 6 and 16 hours in both occluded and non-occluded skin sites. Only the fluocinolone acetonide generic and brand name preparations were different from each other. The spectrophotometric method proved to be equivalent but not superior to the standard human observer method. C1 US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP CONNER, DP (reprint author), UNIFORMED SERV UNIV HLTH SCI,DIV CLIN PHARMACOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. RI Zamani, Kaveh/A-9182-2011 FU PHS HHS [224-88-3006] NR 20 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD AUG PY 1993 VL 33 IS 8 BP 707 EP 711 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LU227 UT WOS:A1993LU22700006 PM 8408730 ER PT J AU MATHEW, M SCHROEDER, LW BROWN, WE AF MATHEW, M SCHROEDER, LW BROWN, WE TI CRYSTAL-STRUCTURE OF DICALCIUM POTASSIUM TRIHYDROGEN BIS(PYROPHOSPHATE) TRIHYDRATE SO JOURNAL OF CRYSTALLOGRAPHIC AND SPECTROSCOPIC RESEARCH LA English DT Article AB The crystal structure of Ca2KH3(P2O7)2 . 3H2O has been determined by single crystal X-ray diffraction. Crystals are monoclinic, space group P2(1)/n with a = 10.518(3), b = 19.253(9), c = 7.340(3)angstrom, beta = 90.07(2)-degrees, and Z = 4. The structure was refined to R = 0.048 and R(w) = 0.044 for 1839 reflections with I greater-than-or-equal-to 3sigma(I). The structure consists of a compact assembly of Ca, K, HP2O7, and H2P2O7 ions and three water molecules arranged in layers perpendicular to the b-axis. The two independent Ca ions and the HP2O7 ion comprise one layer; K and H2P2O7 ions and the three water molecules form an interstitial layer. Coordinations of the two independent Ca ions are quite similar, but the environments of HP2O7 and H2P2O7 ions are quite different, probably due to their locations in different layers. The general structural features are quite similar to those of Ca(NH4)HP2O7. C1 US FDA,BUR RADIOL HLTH,DIV BIOL EFFECTS,ROCKVILLE,MD 20857. RP MATHEW, M (reprint author), NATL INST STAND & TECHNOL,AMER DENT ASSOC HLTH FDN,PAFFENBARGER RES CTR,GAITHERSBURG,MD 20899, USA. NR 12 TC 8 Z9 8 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0277-8068 J9 J CRYST SPECTROSC PD AUG PY 1993 VL 23 IS 8 BP 657 EP 661 DI 10.1007/BF01325190 PG 5 WC Crystallography; Spectroscopy SC Crystallography; Spectroscopy GA LP626 UT WOS:A1993LP62600008 ER PT J AU TORTORELLO, ML GENDEL, SM AF TORTORELLO, ML GENDEL, SM TI FLUORESCENT-ANTIBODIES APPLIED TO DIRECT EPIFLUORESCENT FILTER TECHNIQUE FOR MICROSCOPIC ENUMERATION OF ESCHERICHIA-COLI O157-H7 IN MILK AND JUICE SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MICROCOLONY TECHNIQUE; RAPID ENUMERATION; RAW-MILK; BACTERIA; O157-H7; FOODS; MEAT; MICROORGANISMS; CULTURES; SAMPLES AB In a modification of the direct epifluorescent filter technique (DEFT), direct fluorescent antibody staining was used for the rapid (<1 h), specific enumeration of foodborne Escherichia coli O157:H7 by epifluorescence microscopy. Cell counts obtained by this method (Ab-DEFT) correlated well with DEFt counts obtained by acridine orange staining and with viable plate counts ranging from 10(8) to 10(1) cells per ml for pure cultures in buffer. Ab-DEFT also was effective for counting E. coli O157:H7 cells inoculated into milk and juice; the sensitivity limit was about 10(3) for milk. The highly specific nature of the technique was demonstrated by enumeration of E. coli O157:H7 cells in the presence of large numbers of indigenous spoilage microorganisms in milk. This is the first known demonstration of the combination of DEFT and antibody probe technology for the specific enumeration of a microbe directly in food without a growth or enrichment step. RP TORTORELLO, ML (reprint author), US FDA, NATL CTR FOOD SAFETY & TECHNOL, SUMMIT ARGO, IL 60501 USA. NR 26 TC 27 Z9 28 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 AUG PY 1993 VL 56 IS 8 BP 672 EP 677 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA LU067 UT WOS:A1993LU06700005 ER PT J AU BUCHANAN, RL DEROEVER, CM AF BUCHANAN, RL DEROEVER, CM TI LIMITS IN ASSESSING MICROBIOLOGICAL FOOD SAFETY SO JOURNAL OF FOOD PROTECTION LA English DT Article ID UNITED-STATES; LISTERIA-MONOCYTOGENES; FOODBORNE DISEASE; AEROMONAS-HYDROPHILA; GROWTH TEMPERATURE; RISK-FACTORS; CANADA; BROTH AB Scientific information pertaining to the incidence of foodborne disease and the sources of Pathogenic microorganisms is often limited in relation to the knowledge needed to make informed microbiological food safety decisions. Inherent limitations in the current epidemiological reporting system constrain its usefulness for ascertaining the true incidence of foodborne disease. Additionally, current detection methods are insufficient to make real-time decisions on the microbiological safety of products. An integrated approach that combines enhanced epidemiological data. improved detection methods, detailed knowledge of the behavior of pathogens in food systems, and development of techniques for making quantitative risk assessments is essential for the development of a comprehensive, cost-effective strategy for assuring microbiologically safe foods. C1 US FDA, CTR FOOD SAFETY & APPL NUTR, WASHINGTON, DC 20204 USA. RP BUCHANAN, RL (reprint author), USDA ARS, EASTERN REG RES CTR, MICROBIAL FOOD SAFETY UNIT, 600 E MERMAID LANE, PHILADELPHIA, PA 19118 USA. NR 39 TC 16 Z9 16 U1 1 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 1993 VL 56 IS 8 BP 725 EP 729 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA LU067 UT WOS:A1993LU06700017 ER PT J AU GECAN, JS CICHOWICZ, SM AF GECAN, JS CICHOWICZ, SM TI TOXIC MUSHROOM CONTAMINATION OF WILD MUSHROOMS IN COMMERCIAL DISTRIBUTION SO JOURNAL OF FOOD PROTECTION LA English DT Article AB Poisonings caused by ingestion of toxic, wild-picked morel mushrooms have been reported to the Food and Drug Administration (FDA). Problems occur when collectors of wild mushrooms inadvertently include toxic look-alike species with the edible wild species offered for sale. A 2-year survey conducted by the FDA showed 21% of the morel and 15% of the wild mixed mushrooms were contaminated with toxic look-alike species. These contaminants contain toxins that produce symptoms ranging from dizziness and gastrointestinal distress to liver and heart damage. Present regulatory controls include FDA Import Alerts for morels contaminated with Gyromitra esculenta and Verpa bohemica, a Michigan state regulation requiring licensing of harvesters of wild mushrooms, and an Illinois state regulation prohibiting the sale of wild-picked mushrooms through retail outlets. American consumers, unable to distinguish between edible and toxic look-alike wild mushrooms. may face illness and possibly death from products purchased on the normally well-regulated U.S. consumer market. RP GECAN, JS (reprint author), US FDA,DIV MICROANALYT EVALUAT,WASHINGTON,DC 20204, USA. NR 23 TC 4 Z9 5 U1 1 U2 5 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD AUG PY 1993 VL 56 IS 8 BP 730 EP 734 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA LU067 UT WOS:A1993LU06700018 ER PT J AU ZHANG, PF KLUTCH, M MULLER, J MARCUSSEKURA, CJ AF ZHANG, PF KLUTCH, M MULLER, J MARCUSSEKURA, CJ TI ST-LOUIS ENCEPHALITIS-VIRUS ESTABLISHES A PRODUCTIVE, CYTOPATHIC AND PERSISTENT INFECTION OF SF9 CELLS SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID AEDES; LINES AB The Sf9 cell line, commonly used for gene expression by recombinant baculovirus, has been productively infected by St Louis encephalitis (SLE) virus. a flavivirus. SLE viral infection produced a c.p.e. in the Sf9 cells characterized by giant cells and the presence of 10-fold fewer cells in the infected cultures after the first week of infection compared with uninoculated control cultures. Infected Sf9 cells expressed SLE viral antigens, and intracellular virus particles were observed by electron microscopy. Titres of cell-associated SLE virus rose slightly over an 8 week period, whereas titres of cell-free virus remained stable, suggesting that SLE virus establishes a productive and persistent infection of Sf9 cells. The SLE virus produced by the Sf9 cells could be neutralized by SLE virus-immune mouse ascitic fluid, and no evidence of escape mutants was detected. Sf9 cells persistently infected with SLE virus could be superinfected with a recombinant baculovirus and expressed recombinant antigen. The successful infection of Sf9 cells by SLE virus represents the first report of production of c.p.e. by SLE virus in insect cells under routine cell culture conditions and of the infection of Sf9 cells by a human pathogen. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BETHESDA,MD 20892. NR 29 TC 6 Z9 6 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD AUG PY 1993 VL 74 BP 1703 EP 1708 DI 10.1099/0022-1317-74-8-1703 PN 8 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA LQ264 UT WOS:A1993LQ26400032 PM 8345362 ER PT J AU HANNA, GM LAUCAM, CA AF HANNA, GM LAUCAM, CA TI DETERMINATION OF THE OPTICAL PURITY AND ABSOLUTE-CONFIGURATION OF THREO-METHYLPHENIDATE BY PROTON NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY WITH CHIRAL SOLVATING AGENT SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE THREO-METHYLPHENIDATE; H-1-NMR SPECTROSCOPY; CHIRAL SOLVATING AGENT; ENANTIOMERS; DIASTEREOMERIC SOLVATES; OPTICAL PURITY; ABSOLUTE CONFIGURATIONS ID ENANTIOMERS; RESOLUTION AB The direct determination of both the optical purity and absolute configuration of threo-methylphenidate has been accomplished in a simple, specific, and accurate manner by H-1-NMR spectroscopy. The enantiomeric resonances of threo-methylphenidate were effectively resolved in CDCl3 solution by the addition of the chiral solvating agents (R)-(-)-or (S)-(+)-2,2,2,-trifluoro-1-(9-anthryl)ethanol. Optical purities were determined on the basis of the intensities of the enantiomeric ester methyl proton resonances; the assignment of enantiomeric configurations was based on the relative field positions of these resonances and the examination of molecular models. The analysis of synthetic enantiomeric mixtures of threo-methylphenidate by the proposed NMR method resulted in assay values that agreed closely with the known quantities of each enantiomer in the mixtures tested. The mean +/-SD recovery value for the (2S,2'S)-(-)-threo-enantiomer, amounting to 99.9 +/- 0.6% of added (n = 10), correlated well with that previously found by H-1-NMR spectroscopy with a chiral Eu(III) shift reagent. However, the present approach is simpler, shows less reliance on reagents and solvents of a high purity, and does not require strict anaerobic working conditions. C1 ST JOHNS UNIV,COLL PHARM & ALLIED HLTH PROFESS,JAMAICA,NY 11439. RP HANNA, GM (reprint author), US FDA,DEPT HLTH & HUMAN SERV,NEW YORK REG LAB,850 3RD AVE,BROOKLYN,NY 11239, USA. NR 17 TC 8 Z9 8 U1 0 U2 2 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 AUG PY 1993 VL 11 IS 8 BP 665 EP 670 DI 10.1016/0731-7085(93)80172-W PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA LY055 UT WOS:A1993LY05500006 PM 8257731 ER PT J AU BRENNEMAN, DE PAGE, SW SCHULTZBERG, M THOMAS, FS ZELAZOWSKI, P BURNET, P AVIDOR, R STERNBERG, EM AF BRENNEMAN, DE PAGE, SW SCHULTZBERG, M THOMAS, FS ZELAZOWSKI, P BURNET, P AVIDOR, R STERNBERG, EM TI A DECOMPOSITION PRODUCT OF A CONTAMINANT IMPLICATED IN L-TRYPTOPHAN EOSINOPHILIA-MYALGIA-SYNDROME AFFECTS SPINAL-CORD NEURONAL CELL-DEATH AND SURVIVAL THROUGH STEREOSPECIFIC, MATURATION AND PARTLY INTERLEUKIN-1-DEPENDENT MECHANISMS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PEAK-E; EXPRESSION; INGESTION; CLONING; ACID; CDNA; IDENTIFICATION; NEUROTOXICITY; SUBSTANCE; TISSUES AB The L-tryptophan eosinophilia myalgia syndrome (L-TRP-EMS), an inflammatory syndrome characterized by eosinophilia, myalgias, perimyositis, fasciitis and neuropathies, occurred in epidemic proportions in the United States in the summer and fall of 1989. The neuropathic clinical features in L-TRP EMS are complex and mixed. In the present study, one of the impurities most highly associated with development Of L-TRP EMS, 1,1'-ethylidenebis[L-tryptophan] (EBT), and two of its diastereoisomeric breakdown products, were compared for evidence of neurotoxicity in vitro. In 1-month-old spinal cord cultures derived from fetal mice, synthetic (-)-(1S, 3S)-l-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (1S-beta-C) produced a 30 to 35% loss in numbers of neurons. Toxicity was not apparent after treatment with the R-isomer of the same compound or with the parent compound, EBT. Cotreatment of cultures with 1S-beta-C and neutralizing antiserum to interleukin-1 alpha (IL-1 a), or with 1 S-beta-C and neutralizing antiserum against the murine IL-1 receptor, prevented neuronal cell death associated with 1S-beta-C. Recombinant IL-1 a also produced neuronal killing that was not additive to that observed with the 1S-beta-C treatment. In contrast, in immature spinal cord neuronal cultures, the 1S-beta-C, but not the 1R-beta-C or EBT, prevented the 30% cell death which normally occurs in these cultures. Neither neutralizing anti-IL-1 antibody, nor anti-IL-1 receptor antibody blocked the neuronal survival effect, suggesting that 1 S-beta-C induces neuronal survival through a receptor-mediated mechanism independent of IL-1. The stereospecificity suggests that these effects may be receptor mediated. These studies indicate that the 1 S-beta-C effects on neuronal survival in immature neurons are maturation-dependent, and that although the neurotoxic effects of 1 S-beta-C are receptor-mediated and linked to IL-1 alpha, the neuronal survival-promoting effects are receptor-mediated and independent of IL-1. These data support the hypothesis that 1S-beta-C can cause neuronal cell death, and imply that this compound may play a role in the etiology of some of the neuropathic features Of L-TRP-EMS. C1 NIMH,BLDG 10,ROOM 35231,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. HUDDINGE HOSP,KAROLINSKA INST,CLIN RES CTR,DIV BASIC SCI DEMENTIA,S-14186 HUDDINGE,SWEDEN. NICHHD,DEV & MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RI Schultzberg, Marianne/E-7076-2014 OI Schultzberg, Marianne/0000-0002-8314-0927 NR 46 TC 48 Z9 48 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1993 VL 266 IS 2 BP 1029 EP 1035 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT482 UT WOS:A1993LT48200073 PM 8355179 ER PT J AU BOWYER, JF GOUGH, B BROENING, HW NEWPORT, GD SCHMUED, L AF BOWYER, JF GOUGH, B BROENING, HW NEWPORT, GD SCHMUED, L TI FLUOROGOLD AND PENTAMIDINE INHIBIT THE IN-VITRO AND IN-VIVO RELEASE OF DOPAMINE IN THE STRIATUM OF RAT SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ISOLATED BRAIN-TISSUE; EVOKED RELEASE; NITRIC-OXIDE; NEUROTRANSMITTER RELEASE; H-3 DOPAMINE; ENDOGENOUS DOPAMINE; OMEGA-CONOTOXIN; CAUDATE-NUCLEUS; RABBIT CAUDATE; L-GLUTAMATE AB Fluoro-Gold (FG), first developed as an antifungal/antiparasitic agent, is now also used extensively as a retrograde tracer in histological studies of nervous tissue. The fact that FG is taken up by dopamine (DA) terminals before its retrograde transport to DA cell bodies implies a presynaptic interaction, though the biochemical target(s) and mechanism(s) are unknown. To further elucidate, FG and another aromatic diamidine, pentamidine, were tested on [H-3]DA release and uptake in vitro from striatal slices and synaptosomes. Neither compound affected [H-3]DA uptake in synaptosomes and slices, and neither inhibited DA efflux mediated through reversal of DA uptake mechanisms. NMDA-mediated glutamate-evoked DA release was completely inhibited by either FG (IC50 almost-equal-to 3 muM) or pentamidine (IC50 almost-equal-to 1 muM), and 20 mM K+-evoked DA release was inhibited by similar concentrations but only to 60% of control. Arginine (up to 500 muM) and spermidine (200 muM) failed to reverse 33 muM FG inhibition of either the spontaneous or the glutamate-evoked DA release, indicating that FG inhibition of release was not necessarily via blockade of either nitric oxide generation or spermidine binding to NMDA receptors. Interestingly, FG (33 muM) and pentamidine (10 muM) inhibited 1 and 5 muM D-methamphetamine (METH)-evoked [H-3]DA release to approximately 50% of control, and in striatal synaptosomes, FG (33 muM) and pentamidine (10 muM) inhibited 5 muM METH- and 1.25 mM Ca++-evoked DA release. Additionally, in vivo brain microdialysis supported the in vitro results; 100 muM FG in the microdialysis buffer inhibited 70% of the increase in extracellular DA in the striatum produced by 2.5 mg/kg METH. Furthermore, both compounds blocked the release of [H-3]dihydroxyphenylacetic acid from striatal slices evoked by 50 nM reserpine. Together these data indicate that one mechanism by which FG and pentamidine block DA release, which does not involve depleting vesicular DA stores or the transporter involved in DA uptake and cytosolic release, is direct interaction with vesicles. Therefore, they are potentially useful tools in mechanistic studies on the regulation of vesicular DA release. C1 NATL CTR TOXICOL RES, DIV REPROD & DEV TOXICOL, JEFFERSON, AR 72079 USA. RP BOWYER, JF (reprint author), NATL CTR TOXICOL RES, DIV NEUROTOXICOL, HFT-132, JEFFERSON, AR 72079 USA. NR 48 TC 8 Z9 8 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1993 VL 266 IS 2 BP 1066 EP 1074 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT482 UT WOS:A1993LT48200077 PM 8355181 ER PT J AU JACKSON, CD SHELDON, W AF JACKSON, CD SHELDON, W TI 2-YEAR TOXICITY STUDY OF DOXYLAMINE SUCCINATE IN B6C3F1 MICE SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article ID MOUSE-LIVER TUMORS; RISK ASSESSMENT; THYROID-GLAND; BONE-MARROW; RATS; CARCINOGENESIS; MEGAKARYOCYTES; METHAPYRILENE AB Doxylamine succinate, a commonly used antihistamine, was administered as an admixture in the feed to groups of male and female B6C3F1 mice at dosage levels of 0, 190, 375, and 750 parts per million (ppm) (based on free amine) for 65 weeks (12 per group) or 2 years (48 per group). Survival to terminal sacrifice in the 2-year groups was 85-98% with no significant differences between groups of the same sex. Final body weights of the highest dose group were 3.4% and 8.7% less than controls in males and females, respectively. Doxylamine produced liver lesions in male mice including hepatocellular hypertrophy, atypical hepatocytes, clear cell and mixed cell foci, and necrosis. In females, doxylamine produced liver fatty change, hepatocellular hypertrophy, and necrosis. Doxylamine produced a significant increase in hepatocellular adenomas in the mid- and high-dosage groups of males and in the high-dosage group of females. Thyroid follicular cell hyperplasia and thyroid follicular cell adenomas also were increased in treated mice of both sexes. A treatment-related increase in cytoplasmic alteration of the parotid salivary gland in males and an increased incidence in hyperplasia of the pituitary gland in females were observed. C1 PATHOL ASSOCIATES INC,JEFFERSON,AR. RP JACKSON, CD (reprint author), NATL CTR TOXICOL RES,1 NCTR DR,JEFFERSON,AR 72079, USA. NR 25 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD AUG PY 1993 VL 12 IS 4 BP 311 EP 321 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LZ143 UT WOS:A1993LZ14300001 ER PT J AU DOOLEY, KL HANSEN, EB SHELDON, WG BELAND, FA AF DOOLEY, KL HANSEN, EB SHELDON, WG BELAND, FA TI 14-DAY, REPEAT-DOSE TOXICITY EVALUATION OF ACONIAZIDE ADMINISTERED ORALLY TO MALE AND FEMALE FISCHER 344 RATS SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article ID TUBERCULOSIS AB Aconiazide, a hydrazone derivative of isoniazid, has been proposed for the treatment of tuberculosis. As a first step toward assessing the safety of this drug, the effects of a daily oral 14-day treatment on weight gain, pathology, and several hematologic and clinical chemistry parameters were determined in Fischer 344 (F344) rats. Dosage-related changes in body weight were observed and these became significant at dosages of 500 mg aconiazide/kg body weight. Pathologic lesions involved the sciatic nerve, liver, and bone marrow, with the incidence typically becoming significantly elevated at dosages of 500 mg aconiazide/kg body weight. Aconiazide treatment caused statistically significant changes in certain clinical chemistry and hematologic parameters; however, the values of these were still within the normal range reported for rats of a comparable age. The plasma concentrations of aconiazide were dosage-related, tended to be higher in females, and did not increase with repeated dosing. C1 NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,HFT-110,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DEPT CHEM,JEFFERSON,AR 72079. PATHOL ASSOCIATES INC,JEFFERSON,AR. NR 13 TC 4 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD AUG PY 1993 VL 12 IS 4 BP 329 EP 336 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LZ143 UT WOS:A1993LZ14300003 ER PT J AU GREENMAN, DL MORRISSEY, R GAYLOR, DW ALLABEN, WT AF GREENMAN, DL MORRISSEY, R GAYLOR, DW ALLABEN, WT TI SUBCHRONIC STUDIES OF PYRILAMINE IN B6C3F(1) MICE SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; METHAPYRILENE HYDROCHLORIDE; RATS; ANTIHISTAMINES; TRIPELENNAMINE; THENYLDIAMINE; ASSAY AB The purpose of this study was to determine the effects of subchronic exposure to the antihistamine pyrilamine maleate and to establish dosage levels to use in a 2-year chronic study. A 14-day repeated-dose study in male and female B6C3F1 mice at dietary levels of pyrilamine (as the free base) of 0, 196, 392, 783, 1563, or 3122 ppm revealed no influence on body weight gain and resulted in no deaths, nor abnormal clinical or gross necropsy observations. Parotid gland cell necrosis was more apparent in high-dosage groups than in controls of either gender. Male and female B6C3F1 mice also were administered pyrilamine for 90 days at dietary concentrations of 0, 375, 750, 1500, 3000, or 6000 ppm. Weight gain was markedly suppressed in the 6000 ppm group, but less so at 1500 and 3000 ppm. Parotid gland cell necrosis was apparent in males receiving 750 ppm pyrilamine and above and in females at 1500 ppm and above. Cytomegaly was noted in the parotid glands of both sexes at midlevel dosages but not in control, low-dosage, or high-dosage animals. It was concluded that 1500 ppm pyrilamine would not be life-threatening to B6C3F1 mice in a chronic study. C1 PATHOL ASSOCIATES INC,JEFFERSON,AR. RP GREENMAN, DL (reprint author), NATL CTR TOXICOL RES,OFF SCI COORDINAT,JEFFERSON,AR 72079, USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD AUG PY 1993 VL 12 IS 4 BP 337 EP 345 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LZ143 UT WOS:A1993LZ14300004 ER PT J AU JACKSON, CD CRONIN, GM BROWN, RJ AF JACKSON, CD CRONIN, GM BROWN, RJ TI SUBCHRONIC STUDIES OF TRIPROLIDINE IN FISCHER 344 RATS SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article ID PSEUDOEPHEDRINE AB Triprolidine, used extensively as an antihistamine, was studied for subchronic toxicity by administration as an admixture in the diet to male and female Fischer 344 rats at dosage levels of 0, 156, 312, 625, 1250, and 2500 parts per million (ppm) for 14 days and in a second study at 0, 250, 500, 1000, 2000, and 4000 ppm for 90 days. In the 14-day study, the only sign of toxicity observed either clinically or histologically was a reduction of final body weights (less than 10%) of both male and female rats in the 2500 ppm dosage group associated with reduced food consumption. In the 90-day study, final body weights were reduced, compared to controls, at the higher dosage levels with 4000 ppm resulting in a 20% and 13.4% reduction in males and females, respectively. Target organs were identified as the liver with hepatic fatty change and the parotid salivary gland, which exhibited treatment-related cytoplasmic alterations of the acinar cells. Males were more susceptible than females to both of these effects. These results indicate that rats would tolerate 2000 ppm triprolidine in a 2-year chronic bioassay without significant shortening of life span. C1 PATHOL ASSOCIATES INC,JEFFERSON,AR. RP JACKSON, CD (reprint author), NATL CTR TOXICOL RES,DIV NUTR TOXICOL,1 NCTR DR,JEFFERSON,AR 72079, USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD AUG PY 1993 VL 12 IS 4 BP 359 EP 367 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LZ143 UT WOS:A1993LZ14300006 ER PT J AU CHOU, MW LU, MH PEGRAM, RA GAO, P CAO, SF KONG, J HART, RW AF CHOU, MW LU, MH PEGRAM, RA GAO, P CAO, SF KONG, J HART, RW TI EFFECT OF CALORIC RESTRICTION ON AFLATOXIN-B(1)-INDUCED DNA-SYNTHESIS, AFB(1)-DNA BINDING AND CELL-PROLIFERATION IN FISCHER-344 RATS SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE CALORIC RESTRICTION; AFLATOXIN-B(1)(AFB(1)); AFB(1)-INDUCED DNA SYNTHESIS; AFB(1)-DNA BINDING; CELL PROLIFERATION; FISCHER RATS ID MAMMARY TUMORIGENESIS; LIVER-REGENERATION; CARCINOGENESIS; TISSUES; NUCLEI AB Young adult male Fischer rats maintained on a reduced calorie diet (60% of ad libitum food consumption) for 6 weeks showed a decrease in the binding of aflatoxin B1 (AFB1) to hepatic or renal nuclear DNA and a reduction of AFB1-induced hepatocellular damage. Repeated dosing of rats with AFB1 resulted in the inhibition of hepatic and renal DNA synthesis measured by [H-3]thymidine incorporation. However, the rate of DNA synthesis was greater in ad libitum (AL) rats than in calorically restricted (CR) animals. Three days after AFB1 dosing, the rate of DNA synthesis had recovered to the control level. Cell cycle analyses measured by a flow cytometric method on kidney cells of both AL and CR rats showed that there were no significant changes in cell populations in the S phase between these two groups of rats. AFB1 inhibited the cell proliferation on an average of 33%. The restoration of the cell proliferation in kidney cells was found on the third day after AFB1 dosing. The rate of the regenerative cell proliferation was found to be slightly greater in AL rats than in CR animals. The AFB1-induced regenerative DNA synthesis in both liver and kidney was retarded by CR. RP CHOU, MW (reprint author), NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 28 TC 7 Z9 7 U1 0 U2 0 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 AUG 1 PY 1993 VL 70 IS 1-2 BP 23 EP 33 DI 10.1016/0047-6374(93)90056-W PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA LT099 UT WOS:A1993LT09900002 PM 8231286 ER PT J AU KOCSIS, E TRUS, BL STEVEN, AC SMITH, PR HANNAH, JH BRENNAN, MJ KESSEL, M AF KOCSIS, E TRUS, BL STEVEN, AC SMITH, PR HANNAH, JH BRENNAN, MJ KESSEL, M TI ORIENTATION OF PORIN CHANNELS IN THE OUTER-MEMBRANE OF BORDETELLA-PERTUSSIS SO MOLECULAR MICROBIOLOGY LA English DT Review ID ESCHERICHIA-COLI; 3-DIMENSIONAL RECONSTRUCTION; ELECTRON-MICROGRAPHS; PROTEIN PHOE; RESOLUTION; TOPOLOGY; MICROSCOPY; PARTICLES; GENE; OMPC AB We have examined the surface topography and channel connectivity, of a naturally crystalline porin that is known to be functional, and whose structure has not been perturbed by detergent extraction. A three-dimensional density map, calculated from two independent tilt series of negatively stained cell envelopes, reveals three separate channels per trimer on one side (the 'smooth' side), and a single common opening at the other ('rough') side. This arrangement is consistent with the molecular structures recently determined at high resolution by X-ray crystallography for three other porins after detergent solubilization, and implies that the Bordetella pertussis porin may have the same kind of folding. Surface relief maps calculated from electron micrographs of cell envelopes contrasted by unidirectional shadowing clearly show that the side with single opening (i.e. the rough side) represents the external surface. C1 NATL INST ARTHRIT MUSCULOSKELETAL & SKIN DIS,STRUCT BIOL LAB,BETHESDA,MD 20892. US FDA,DIV BACTERIAL PROD,BETHESDA,MD 20892. NYU,SCH MED,DEPT CELL BIOL,NEW YORK,NY 10016. UNIV MARYLAND,DEPT MICROBIOL,COLL PK,MD 20742. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MEMBRANE & ULTRASTRUCT RES,IL-91010 JERUSALEM,ISRAEL. NIH,DIV COMP RES & TECHNOL,COMP SYST LAB,BETHESDA,MD 20892. NR 41 TC 9 Z9 9 U1 2 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 1993 VL 9 IS 3 BP 469 EP 476 DI 10.1111/j.1365-2958.1993.tb01708.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA LQ843 UT WOS:A1993LQ84300008 PM 8412696 ER PT J AU ZMUDZKA, BZ STRICKLAND, AG MILLER, SA VALERIE, K DALLACQUA, F BEER, JZ AF ZMUDZKA, BZ STRICKLAND, AG MILLER, SA VALERIE, K DALLACQUA, F BEER, JZ TI ACTIVATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS PROMOTER BY UVA RADIATION IN COMBINATION WITH PSORALENS OR ANGELICINS SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID LONG TERMINAL REPEAT; ULTRAVIOLET-RADIATION; DNA DAMAGE; INVIVO ACTIVATION; CELL-LINE; PSORIASIS; TYPE-1; EXPRESSION; INDUCTION; 8-METHOXYPSORALEN AB The effects of mono- and bifunctional furocoumarins plus UVA radiation (PUVA and related treatments) on the human immunodeficiency virus-1 (HIV-1) promoter were studied using HeLa cells stably transfected with the chloramphenicol acetyl transferase gene under the control of the HIV-1 promoter. The experiments were performed with three psoralens (5-methoxypsoralen, 5-MOP; 8-methoxypsoralen, 8-MOP; and 4'-aminomethyl-4,8,5'-trimethyl-psoralen, AMT) and four angelicins (angelicin: 4,5'-dimethylangelicin, 4,5'-DMA; 6,4'-dimethylangelicin, 6,4'-DMA; and 4,6,4'-trimethylangelicin, TMA). The drugs alone and UVA radiation alone showed no effect on the HIV promoter. However, when the cells were incubated with the furocoumarins at 0.1-40 mug/mL and then irradiated, the HIV promoter was activated in distinct fluence ranges, i.e. (1) no promoter activity was discernible at low fluences (e.g. at 0.1 mug/mL of 8-MOP up to 100 kJ/m2), (2) as the fluence was increased, the promoter activity increased to reach a maximum (10-50-fold with respect to the unexposed samples), and (3) as the fluence was further increased, the promoter activity decreased. Similar (although shifted on the fluence scale) patterns were observed with either >340-nm UVA radiation or with UVA radiation contaminated with a small amount of UVB radiation (typical for PUVA lamps). The effective fluences were inversely related to the drug concentration. Experiments with 5-MOP and 8-MOP indicated reciprocity of the drug concentration and radiation fluence. The HIV promoter response patterns were similar for monofunctional angelicins and bifunctional psoralens. This indicated that the furocoumarin-DNA cross-links are not a prerequisite for the promoter activation and that the monoadducts suffice to elicit the HIV promoter response. The HIV promoter-activating effectiveness of different drugs correlated with their photosensitizing potential. Thus, among psoralens the effectiveness order was AMT > 5-MOP > 8-MOP, and among angelicins: TMA > 6,4'-DMA > 4,5'-DMA > angelicin. The effectiveness did not vary substantially for 5-MOP, 8-MOP, 4,5'-DMA, and 6,4'-DMA. The combined drug and UVA radiation doses were higher than those that elicit cellular responses or those that may be received by the human white blood cells during extracorporeal PUVA therapy (photopheresis). C1 UNIV PADUA,DIPARTIMENTO SCI FARMACEUT,I-35100 PADUA,ITALY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT RADIAT ONCOL,RICHMOND,VA 23298. RP ZMUDZKA, BZ (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857, USA. NR 33 TC 28 Z9 28 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 AUG PY 1993 VL 58 IS 2 BP 226 EP 232 DI 10.1111/j.1751-1097.1993.tb09553.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LT882 UT WOS:A1993LT88200013 PM 8415914 ER PT J AU TOLLEFSON, L AF TOLLEFSON, L TI MULTIPLE CHEMICAL-SENSITIVITY - CONTROLLED SCIENTIFIC STUDIES AS PROOF OF CAUSATION SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT SYMP ON MULTIPLE CHEMICAL SENSITIVITIES CY NOV 19-20, 1992 CL ARLINGTON, VA ID ASPARTAME RP TOLLEFSON, L (reprint author), US FDA,DIV MKT STUDIES HFS-725,200 C ST SW,WASHINGTON,DC 20204, USA. NR 18 TC 11 Z9 11 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 1993 VL 18 IS 1 BP 32 EP 43 DI 10.1006/rtph.1993.1042 PG 12 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA LR083 UT WOS:A1993LR08300004 PM 8234917 ER PT J AU KREWSKI, D GAYLOR, DW SOMS, AP SZYSZKOWICZ, M AF KREWSKI, D GAYLOR, DW SOMS, AP SZYSZKOWICZ, M TI AN OVERVIEW OF THE REPORT - CORRELATION BETWEEN CARCINOGENIC POTENCY AND THE MAXIMUM TOLERATED DOSE - IMPLICATIONS FOR RISK ASSESSMENT SO RISK ANALYSIS LA English DT Review DE CARCINOGENIC POTENCY; CARCINOGEN BIOASSAY; MAXIMUM TOLERATED DOSE; MUTAGENICITY; TOXICITY ID ANIMAL BIOASSAYS; RODENT CARCINOGENS; CHEMICAL CARCINOGENESIS; CHRONOLOGICAL SUPPLEMENT; SALMONELLA MUTAGENICITY; ACUTE TOXICITY; RANKING; HUMANS; DATABASE; PREDICTION AB Current practice in carcinogen bioassay calls for exposure of experimental animals at doses up to and including the maximum tolerated dose (MTD). Such studies have been used to compute measures of carcinogenic potency such as the TD50 as well as unit risk factors such as q1* for predicting low-dose risks. Recent studies have indicated that these measures of carcinogenic potency are highly correlated with the MTD. Carcinogenic potency has also been shown to be correlated with indicators of mutagenicity and toxicity. Correlation of the MTDs for rats and mice implies a corresponding correlation in TD50 values for these two species. The implications of these results for cancer risk assessment are examined in light of the large variation in potency among chemicals known to induce tumors in rodents. C1 CARLETON UNIV,DEPT MATH & STAT,OTTAWA K1A 0L2,ONTARIO,CANADA. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV WISCONSIN,CTR MATH SCI,MADISON,WI 53705. UNIV WISCONSIN,DEPT MATH SCI,MILWAUKEE,WI 53201. RP KREWSKI, D (reprint author), HLTH & WELF CANADA,HLTH PROTECT BRANCH,OTTAWA K1A 0L2,ONTARIO,CANADA. NR 119 TC 27 Z9 27 U1 0 U2 1 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 AUG PY 1993 VL 13 IS 4 BP 383 EP 398 DI 10.1111/j.1539-6924.1993.tb00738.x PG 16 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA LX892 UT WOS:A1993LX89200003 PM 8234946 ER PT J AU SEIDMAN, AD NORTON, L REICHMAN, BS CROWN, JPA YAO, TJ HEELAN, R HAKES, TB LEBWOHL, DE GILEWSKI, TA SURBONE, A CURRIE, V HUDIS, CA KLECKER, R JAMISDOW, C COLLINS, J QUINLIVAN, S BERKERY, R TOOMASI, F CANETTA, R FISHERMAN, J ARBUCK, S AF SEIDMAN, AD NORTON, L REICHMAN, BS CROWN, JPA YAO, TJ HEELAN, R HAKES, TB LEBWOHL, DE GILEWSKI, TA SURBONE, A CURRIE, V HUDIS, CA KLECKER, R JAMISDOW, C COLLINS, J QUINLIVAN, S BERKERY, R TOOMASI, F CANETTA, R FISHERMAN, J ARBUCK, S TI PRELIMINARY EXPERIENCE WITH PACLITAXEL (TAXOL(R)) PLUS RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR IN THE TREATMENT OF BREAST-CANCER SO SEMINARS IN ONCOLOGY LA English DT Article ID PHASE-I TRIAL; EVERY 21 DAYS; METASTATIC MELANOMA; RESISTANCE; AGENT; CELLS; DRUGS C1 US FDA,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,WALLINGFORD,CT. NCI,DIV CANC TREATMENT,INVESTIGAT DRUG BRANCH,BETHESDA,MD 20892. RP SEIDMAN, AD (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,HOWARD BLDG,ROOM 1009,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA-09207-14, 1-CM07311] NR 23 TC 64 Z9 64 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1993 VL 20 IS 4 SU 3 BP 40 EP 45 PG 6 WC Oncology SC Oncology GA LT571 UT WOS:A1993LT57100005 PM 7688145 ER PT J AU FLYNN, TJ GIBSON, RR JOHANNESSEN, JN AF FLYNN, TJ GIBSON, RR JOHANNESSEN, JN TI EVIDENCE THAT SPONTANEOUS SITUS-INVERSUS IN CULTURED NEURAL PLATE STAGED RAT EMBRYOS IS ADDITIVE WITH AND NOT MEDIATED THROUGH ADRENERGIC-MECHANISMS SO TERATOLOGY LA English DT Article ID SPRAGUE-DAWLEY RATS; NITROUS-OXIDE; BODY ASYMMETRY; HEART; ORGANOGENESIS; SIDEDNESS; PERIOD; CREST; TUBE AB Approximately 50% of untreated presomite rat embryos in culture have demonstrated inversions of cardiac looping (laeval instead of dextral) or tail flexure (left-sided instead of right-sided), or both. This spontaneous situs inversus (SI) was not accompanied by growth inhibition or any other observable defects. The incidence of SI was directly related to the stage at dissection, and all heart defects and most flexure defects were eliminated by delaying explantation to the early somite stage. The incidence of SI was not lowered significantly either by removal of endogenous catecholamines from the culture serum by dialysis or by inclusion of alpha- or beta-adrenergic antagonists in the medium. However, the alpha-adrenergic agonist L-phenylephrine (50 mug/ml) increased the incidence of SI to 73%. These findings appear to rule out adrenergic mechanisms as a cause of spontaneous SI in cultured, neural plate-staged rat embryos but suggest a mechanism, yet unknown, that is additive with SI induced by alpha-adrenergic agonists. The low incidence of non-SI-related defects suggests that the high incidence of SI is not an artifact of suboptimal culture conditions. The virtual absence of SI in embryos cultured in bovine serum, a medium in which overall embryonic growth and development were retarded, provides further evidence against nonspecific artifacts. (C) 1993 Wiley-Liss, Inc.* RP FLYNN, TJ (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL STUDIES,MOD-1,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. OI Flynn, Thomas/0000-0002-7248-0643 NR 27 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD AUG PY 1993 VL 48 IS 2 BP 161 EP 168 DI 10.1002/tera.1420480210 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA LQ401 UT WOS:A1993LQ40100009 PM 8105553 ER PT J AU DJURIC, Z POTTER, DW CULP, SJ LUONGO, DA BELAND, FA AF DJURIC, Z POTTER, DW CULP, SJ LUONGO, DA BELAND, FA TI FORMATION OF DNA-ADDUCTS AND OXIDATIVE DNA-DAMAGE IN RATS TREATED WITH 1,6-DINITROPYRENE SO CANCER LETTERS LA English DT Article DE P-32-POSTLABELING; MASS SPECTROMETRY; N-(DEOXYGUANOSIN-8-YL)-1-AMINO-6-NITROPYRENE; 5-HYDROXYMETHYL-2'-DEOXYURIDINE; 8-HYDROXY-2'-DEOXYGUANOSINE ID CARCINOGENICITY; DINITROPYRENES; REDUCTION; INDUCTION; 1-NITRO-6-NITROSOPYRENE; TUMORIGENICITY; BENZOPYRENE; 1-NITROPYRENE; CARCINOMA; BINDING AB In vitro metabolism studies have indicated that the tumorigenic environmental pollutant 1,6-dinitropyrene has the potential to bind covalently to DNA and to induce oxidative DNA damage. We have determined if 1,6-dinitropyrene treatment will cause both types of DNA damage in vivo. Female Sprague-Dawley rats were given a single intraperitoneal injection of 1,6-dinitropyrene, and covalent DNA adduct formation, as indicated by the presence of N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, and oxidative DNA damage, as indicated by increases in 5-hydroxymethyl-2'-deoxyuridine and 8-hydroxy-2'-deoxyguanosine, were assessed at 3, 12, 24 and 48 h after dosing. P-32-postlabeling analyses of DNA isolated from liver, mammary gland, bladder and nucleated blood cells indicated the formation of N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, with the levels being highest in the bladder. 5-hydroxymethyl-2'-deoxyuridine was detected in DNA from each of these tissues, and the levels of this oxidized nucleoside were higher in the mammary glands and livers of 1,6-dinitropyrene-treated rats. 1,6-Dinitropyrene dosing did not affect the levels of 8-hydroxy-2'-deoxyguanosine in these two tissues. These results indicate that exposure to 1,6-dinitropyrene can result in increased levels of 5-hydroxymethyl-2'-deoxyuridine in addition to covalent DNA adduct formation. C1 WAYNE STATE UNIV,DEPT INTERNAL MED,DETROIT,MI 48201. ROHM & HAAS CO,DIV TOXICOL,SPRING HOUSE,PA 19477. NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. RI Djuric, Zora/H-5147-2013 OI Djuric, Zora/0000-0002-8886-8853 NR 25 TC 9 Z9 10 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 30 PY 1993 VL 71 IS 1-3 BP 51 EP 56 DI 10.1016/0304-3835(93)90096-R PG 6 WC Oncology SC Oncology GA LU536 UT WOS:A1993LU53600009 PM 8364899 ER PT J AU LOUIE, KK PACCAGNELLA, AM OSEI, WD LIOR, H FRANCIS, BJ OSTERHOLM, MT AF LOUIE, KK PACCAGNELLA, AM OSEI, WD LIOR, H FRANCIS, BJ OSTERHOLM, MT TI SALMONELLA SEROTYPE TENNESSEE IN POWDERED MILK-PRODUCTS AND INFANT FORMULA - CANADA AND UNITED-STATES, 1993 (REPRINTED FROM MMWR, VOL 42, PG 516-517, 1993) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 BRITISH COLUMBIA CTR DIS CONTROL,VANCOUVER,BC,CANADA. LAB CTR DIS CONTROL,NATL LAB ENTER PATHOGENS,OTTAWA,ON,CANADA. ILLINOIS DEPT PUBL HLTH,SPRINGFIELD,IL. MINNESOTA DEPT HLTH,MINNEAPOLIS,MN. US FDA,CTR FOOD SAFETY & APPL NUTR,MINNEAPOLIS,MN. CTR DIS CONTROL,NATL CTR INFECT DIS,DIV BACTERIAL & MYCOT DIS,ATLANTA,GA 30333. RP LOUIE, KK (reprint author), BOUNDARY HLTH UNIT,SURREY,BC,CANADA. NR 3 TC 7 Z9 7 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 28 PY 1993 VL 270 IS 4 BP 432 EP 432 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LN426 UT WOS:A1993LN42600008 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI DIETARY-SUPPLEMENT USE - SIGNIFICANT INFORMATION IN THE MEDICAL HISTORY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP NIGHTINGALE, SL (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 2 TC 1 Z9 1 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 JUL 28 PY 1993 VL 270 IS 4 BP 454 EP 454 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LN426 UT WOS:A1993LN42600023 PM 8320781 ER PT J AU WOERNER, AM MARCUSSEKURA, CJ AF WOERNER, AM MARCUSSEKURA, CJ TI CHARACTERIZATION OF A DNA-BINDING DOMAIN IN THE C-TERMINUS OF HIV-1 INTEGRASE BY DELETION MUTAGENESIS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; ESCHERICHIA-COLI; RETROVIRAL INTEGRASE; VIRAL-DNA; PROTEIN INVITRO; TYPE-1; EXPRESSION; SEQUENCES; IDENTIFICATION AB The integrase (IN) protein of human immunodeficiency virus type 1 (HIV-1) catalyzes site-specific cleavage of 2 bases from the viral long terminal repeat (LTR) sequence yet it binds DNA with little DNA sequence specificity. We have previously demonstrated that the C-terminal half of IN (amino acids 154 - 288) possesses a DNA binding domain. In order to further characterize this region, a series of clones expressing truncated forms of IN as N-terminal fusion proteins in E. coli were constructed and analyzed by Southwestern blotting. Proteins containing amino acids 1 - 263, 1 - 248 and 170 - 288 retained the ability to bind DNA, whereas a protein containing amino acids 1 - 180 showed no detectable DNA binding. This defines a DNA binding domain contained within amino acids 180 - 248. This region contains an arrangement of 9 lysine and arginine residues each separated by 2 - 4 amino acids (KxxxKxxxKxxxxRxxxRxxRxxxxKxxxKxxxK), spanning amino acids 211 - 244, which is conserved in all HIV-1 isolates. A clone expressing full-length IN with a C-terminal fusion of 16 amino acids was able to bind DNA comparably to a cloned protein with a free C-terminus, and an IN-specific monoclonal antibody which recognizes an epitope contained within amino acids 264 - 279 was unable to block DNA binding, supporting the evidence that a region necessary for binding lies upstream of amino acid 264. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892. NR 40 TC 112 Z9 113 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 25 PY 1993 VL 21 IS 15 BP 3507 EP 3511 DI 10.1093/nar/21.15.3507 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ083 UT WOS:A1993LQ08300024 PM 8346030 ER PT J AU SHAIKH, B MOATS, WA AF SHAIKH, B MOATS, WA TI LIQUID-CHROMATOGRAPHIC ANALYSIS OF ANTIBACTERIAL DRUG RESIDUES IN FOOD-PRODUCTS OF ANIMAL ORIGIN SO JOURNAL OF CHROMATOGRAPHY LA English DT Review ID SOLID-PHASE EXTRACTION; FLUORESCENCE HPLC DETERMINATION; THERMOSPRAY MASS-SPECTROMETRY; ULTRAVIOLET-VISIBLE DETECTION; PENICILLIN-G; BOVINE-MILK; OXYTETRACYCLINE RESIDUES; CHEMICAL-ANALYSIS; THIN-LAYER; CHLORTETRACYCLINE RESIDUES AB This paper reviews recent developments in the liquid chromatographic (LC) methods of analysis for the residues of antibiotics (aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, macrolides, beta-lactams, etc.) in food products of animal origin. The review also covers clean-up procedures, such as, ultrafiltration, liquid-liquid partition. solid-phase extraction. immunoaffinity, and matrix solid-phase dispersion, for use as extraction, deproteination, and concentration steps. The LC methods offer considerable potential for rapid automated analysis, and some may be used as direct screening for residues in meat and milk. C1 USDA ARS,BELTSVILLE AGR RES CTR,MEAT SCI LAB,BELTSVILLE,MD 20705. RP SHAIKH, B (reprint author), US FDA,CTR VET MED,BARC E,BLDG 328A,BELTSVILLE,MD 20705, USA. NR 96 TC 57 Z9 58 U1 2 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD JUL 23 PY 1993 VL 643 IS 1-2 BP 369 EP 378 DI 10.1016/0021-9673(93)80573-Q PG 10 WC Chemistry, Analytical SC Chemistry GA LP651 UT WOS:A1993LP65100039 PM 8360305 ER PT J AU MERKATZ, RB TEMPLE, R SOBEL, S FEIDEN, K KESSLER, DA AF MERKATZ, RB TEMPLE, R SOBEL, S FEIDEN, K KESSLER, DA TI WOMEN IN CLINICAL-TRIALS OF NEW DRUGS - A CHANGE IN FOOD-AND-DRUG-ADMINISTRATION POLICY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ORAL-CONTRACEPTIVE STEROIDS; SEX-DIFFERENCES; PHARMACOKINETICS; METABOLISM; DISPOSITION; GENDER; ADENOCARCINOMA; VAGINA; AGE RP MERKATZ, RB (reprint author), US FDA,HS-1,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 46 TC 142 Z9 143 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 22 PY 1993 VL 329 IS 4 BP 292 EP 296 DI 10.1056/NEJM199307223290429 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA LM682 UT WOS:A1993LM68200036 PM 8305004 ER PT J AU FU, PP ZHANG, YM MAO, YL VONTUNGELN, LS KIM, YM JUNG, HW JUN, MJ AF FU, PP ZHANG, YM MAO, YL VONTUNGELN, LS KIM, YM JUNG, HW JUN, MJ TI RELATIONSHIPS OF STRUCTURES OF NITRO-POLYCYCLIC AROMATIC-HYDROCARBONS WITH HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY RETENTION ORDER SO JOURNAL OF CHROMATOGRAPHY LA English DT Article ID CHIRAL STATIONARY PHASE; K-REGION DIHYDRODIOL; BACTERIAL MUTAGENICITY; MONONITRO DERIVATIVES; MICROSOMAL METABOLISM; DIOL ENANTIOMERS; MONO-OL; SEPARATION; BENZANTHRACENE; BENZOPYRENE AB Forty six structurally related nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) and their corresponding parent PAHs were employed to study the relationships between structure and HPLC retention time. Using reversed-phase HPLC, larger molecules had longer retention times, while saturation of the aromatic rings shortened the retention time. Isomers with a perpendicular nitro group had shorter retention times than if the nitro substituent was parallel to the ring system. The addition of a nitro group caused a substantial decrease in retention time when compared to its parent PAH. When using normal-phase HPLC, an additional benzo ring increased the retention time. The presence of one or two nitro groups on the molecule also increased the retention time, while saturation of a benzo ring decreased the retention time. These results suggest that the polarity of the PAH or nitro-PAH is the principal factor for determining its HPLC retention time. C1 SHANGHAI AGR COLL,DEPT ANIM SCI,SHANGHAI,PEOPLES R CHINA. SOOCHOW UNIV,DEPT CHEM,TAIPEI,TAIWAN. YONSEI UNIV,DEPT CHEM,SEOUL,SOUTH KOREA. RP FU, PP (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 32 TC 13 Z9 13 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD JUL 16 PY 1993 VL 642 IS 1-2 BP 107 EP 116 DI 10.1016/0021-9673(93)80080-R PG 10 WC Chemistry, Analytical SC Chemistry GA LN765 UT WOS:A1993LN76500010 ER PT J AU MALOZOWSKI, S AF MALOZOWSKI, S TI GYNECOMASTIA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP MALOZOWSKI, S (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 15 PY 1993 VL 329 IS 3 BP 209 EP 209 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LL460 UT WOS:A1993LL46000022 PM 8390619 ER PT J AU BEAUCAGE, SL IYER, RP AF BEAUCAGE, SL IYER, RP TI THE SYNTHESIS OF MODIFIED OLIGONUCLEOTIDES BY THE PHOSPHORAMIDITE APPROACH AND THEIR APPLICATIONS SO TETRAHEDRON LA English DT Review ID SOLID-PHASE SYNTHESIS; HUMAN-IMMUNODEFICIENCY-VIRUS; PHOSPHATE-METHYLATED DNA; SUGAR-MODIFIED OLIGONUCLEOTIDES; ALPHA-ANOMERIC OLIGODEOXYRIBONUCLEOTIDES; EFFICIENT CHEMICAL SYNTHESIS; NUCLEAR-MAGNETIC-RESONANCE; ECORI RECOGNITION SEQUENCE; POTENTIAL ANTISENSE AGENTS; BASE-PAIRING PROPERTIES RP BEAUCAGE, SL (reprint author), US FDA, CTR BIOL EVALUAT & RES, DIV BIOCHEM & BIOPHYS, BETHESDA, MD 20892 USA. NR 597 TC 303 Z9 303 U1 1 U2 40 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JUL 9 PY 1993 VL 49 IS 28 BP 6123 EP 6194 DI 10.1016/S0040-4020(01)87958-8 PG 72 WC Chemistry, Organic SC Chemistry GA LL743 UT WOS:A1993LL74300001 ER PT J AU MANOJ, NR DE, PP DE, SK AF MANOJ, NR DE, PP DE, SK TI SELF-CROSS-LINKABLE PLASTIC-RUBBER BLEND SYSTEM BASED ON POLY(VINYL CHLORIDE) AND ACRYLONITRILE-CO-BUTADIENE RUBBER SO JOURNAL OF APPLIED POLYMER SCIENCE LA English DT Article AB That the melt-mixed blend of poly (vinyl chloride) and acrylonitrile-co-butadiene rubber becomes crosslinked during high-temperature molding is evident from Monsanto rheometric, solvent swelling, and infrared spectroscopic studies. Dynamic mechanical analysis shows that such a self-crosslinkable plastic-rubber blend is miscible in different blend ratios. The degree of crosslinking depends on the blend ratios and the molding conditions. The crosslinking reaction involves the allylic chlorine sites in poly (vinyl chloride) and the -C=N group in the nitrile rubber. C1 INDIAN INST TECHNOL,CTR RUBBER TECHNOL,KHARAGPUR 721302,W BENGAL,INDIA. US FDA,DIV MECH & MAT SCI,CTR DEVICES & RADIOL RES,ROCKVILLE,MD 20857. NR 18 TC 28 Z9 28 U1 0 U2 3 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 JUL 5 PY 1993 VL 49 IS 1 BP 133 EP 142 DI 10.1002/app.1993.070490116 PG 10 WC Polymer Science SC Polymer Science GA LG391 UT WOS:A1993LG39100016 ER PT J AU DEBINSKI, W PURI, RK KREITMAN, RJ PASTAN, I AF DEBINSKI, W PURI, RK KREITMAN, RJ PASTAN, I TI A WIDE-RANGE OF HUMAN CANCERS EXPRESS INTERLEUKIN-4 (IL4) RECEPTORS THAT CAN BE TARGETED WITH CHIMERIC TOXIN COMPOSED OF IL4 AND PSEUDOMONAS EXOTOXIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUSION PROTEIN; RECOMBINANT IMMUNOTOXIN; ESCHERICHIA-COLI; ANIMAL TOXICITY; TUMOR-CELLS; CYTOTOXICITY; AERUGINOSA; SEQUENCES; CARCINOMA; DOMAINS AB A chimeric toxin has been constructed by fusion of a gene encoding human interleukin 4 (hIL4) to a gene encoding a mutant form of Pseudomonas exotoxin A (PE) which cannot bind to its receptors (PE4E). The chimeric gene was expressed in Escherichia coli where large amounts of the chimeric toxin, hIL4-PE4E, was produced. Purified hIL4-PE4E was very cytotoxic to cancer cell lines of both hematopoietic and solid tumor origin. In the HUT 102 T cell leukemia and Daudi B cell lymphoma cell lines, protein synthesis was inhibited by 50% (ID50) at a hIL4-PE4E concentration of 2 and 7 ng/ml (25 and 86 pM, respectively). hIL4-PE4E was also very cytotoxic to cell lines derived from carcinomas of the colon, breast, stomach, liver, adrenals, and prostate, as well as melanoma and epidermoid carcinoma, indicating that hIL4 receptors are widely expressed on human malignancies. We also found that human phytohemagglutinin- activated peripheral blood lymphocytes were extremely sensitive to hIL4-PE4E with an ID50 of 0.2 ng/ml (2.5 pM). The cytotoxic action of hIL4-PE4E was specific because it was blocked by an excess of hIL4 and not of human interleukin 2. In addition, hIL4-PE4ED553, an enzymatically inactive form of the chimeric toxin, was not cytotoxic. These results suggest that the hIL4 receptor may be a target for therapy in malignant and immunologic disorders using hIL4 chimeric toxin. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20892. NR 32 TC 68 Z9 68 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1993 VL 268 IS 19 BP 14065 EP 14070 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500044 PM 8314773 ER PT J AU PIPKIN, JL HINSON, WG LYNCOOK, LE FEUERS, RJ BURNS, ER HART, R DUFFY, PF CASCIANO, DA AF PIPKIN, JL HINSON, WG LYNCOOK, LE FEUERS, RJ BURNS, ER HART, R DUFFY, PF CASCIANO, DA TI HISTONE VARIANTS, H(1) SUBTYPES AND OTHER CHROMATIN PROTEINS AS BIOMARKERS OF AGE AND CALORIC RESTRICTION IN RATS SO AGE LA English DT Article ID MOBILITY-GROUP PROTEINS; DRUG-METABOLIZING ENZYMES; CELL-CYCLE; DIETARY RESTRICTION; FISCHER-344 RAT; FREE UBIQUITIN; PHOSPHORYLATION; LIVER; MOUSE; SPERMATOGENESIS AB The synthesis and phosphorylation levels of basic chromatin proteins from cell cycle phases of dividing bone marrow cells in Fischer 344 rats were investigated by gel electrophoresis. Two groups of rats, young ad libitum (Y/A 3 mo.) and old ad libitum (O/AL 28 mo.), had free access to rat chow, and a third group of old rats was maintained on a calorie-restricted intake (O/CR 28 mo.). Histone H-1 subtypes a, b and c from combined S+G2 phase revealed highest amounts of [H-3] lysine incorporation in Y/AL, lowest in O/AL, and intermediate levels in O/CR animals, while subtypes e and I-degrees were highest in O/AL, lowest in Y/AL, and mid level in O/CR. The P-32-orthophosphate incorporation of these subtypes followed a parallel scenario as with lysine. Histone H-4 variants from S phase demonstrated the highest levels of lysine labeling in O/AL, lowest in Y/AL and intermediate levels in O/CR. The H-1 variants were similar in synthesis patterns to H-4 variants but less dramatic. Minor histone variants M2, M3 and M4 manifested most synthesis in O/AL, least in Y/AL and mid levels in O/CR. Conversely, M1 synthesis was high in Y/AL, low in O/AL and modest in O/CR. Ubiquitin followed a similar pattern in lysine labeling to M1 and A24 which was inversely proportional to ubiquitin. The metabolic activity of these basic proteins in O/CR exemplifies a condition characteristic of Y/AL animals modulated by age and diet dependent factors. C1 UNIV ARKANSAS MED SCI HOSP,DEPT ANAT,LITTLE ROCK,AR 72205. RP PIPKIN, JL (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV GENET TOXICOL,JEFFERSON,AR 72079, USA. NR 58 TC 3 Z9 3 U1 2 U2 5 PU AMER AGING ASSOC PI CHESTER PA 2129 PROVIDENCE AVENUE, CHESTER, PA 19013 SN 0161-9152 J9 AGE JI Age PD JUL PY 1993 VL 16 IS 3 BP 97 EP 103 DI 10.1007/BF02436141 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA MG022 UT WOS:A1993MG02200004 ER PT J AU SHADDOCK, JG FEUERS, RJ CASCIANO, DA AF SHADDOCK, JG FEUERS, RJ CASCIANO, DA TI AGING AND ENZYME-INDUCTION - EFFECT ON CHEMICALLY-INDUCED DNA-REPAIR IN NONPROLIFERATING FISCHER F344 RAT HEPATOCYTES SO AGE LA English DT Article ID DRUG-METABOLIZING ENZYMES; CALORIC RESTRICTION; ASSAY; ACTIVATION; CULTURES; CARCINOGENS; CYTOCHROME-P-450; AFLATOXIN-B1 AB Several studies indicate that cancer and other diseases increase as an animal ages. The reasons for these observations are unclear and some have suggested that accumulation of DNA damage and the ability to remove that damage may be responsible. The purpose of this study has been to measure the effect of aging and enzyme induction on the genotoxicity of four carcinogens, representing four different classes of chemicals, in the in vitro rat hepatocyte/DNA repair assay. Hepatocyte cultures were isolated from untreated young male Fischer (F344) rats and old male F344 rats which were either untreated or Aroclor-induced (ARO). Cultures from the untreated old rats, exposed to 2-acetylaminofluorene (2-AAF), aflatoxin B1 (AFB1), 7,12-dimethylbenz[a]anthracene (DMBA) and dimethylnitrosamine (DMN), exhibited age-dependent decreases in DNA excision repair of 75%,49%,40% and 48%, respectively, when compared to untreated young rats. In contrast, cultures from ARO-induced old rats exhibited significant increases in DNA repair of 78%, 43%, 54% and 44% with 2-AAF, AFB1, DMBA and DMN, respectively, when compared to results from untreated old F344 rats. These data indicate that the observed age-dependent decrease in DNA excision repair in the untreated old F344 rats may not be directly related to the DNA repair process, but to the levels of hepatic xenobiotic metabolizing enzymes responsible for the conversion of potentially toxic chemicals to DNA damaging species. C1 UNIV ARKANSAS MED SCI HOSP,DEPT ANAT,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT TOXIKOL,LITTLE ROCK,AR 72205. RP SHADDOCK, JG (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,DIV GENET TOXICOL,JEFFERSON,AR 72079, USA. NR 34 TC 1 Z9 1 U1 1 U2 1 PU AMER AGING ASSOC PI CHESTER PA 2129 PROVIDENCE AVENUE, CHESTER, PA 19013 SN 0161-9152 J9 AGE JI Age PD JUL PY 1993 VL 16 IS 3 BP 105 EP 111 DI 10.1007/BF02436142 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA MG022 UT WOS:A1993MG02200005 ER PT J AU BRIGHT, RA MOORE, RM JENG, LL SHARKNESS, CM HAMBURGER, SE HAMILTON, PM AF BRIGHT, RA MOORE, RM JENG, LL SHARKNESS, CM HAMBURGER, SE HAMILTON, PM TI THE PREVALENCE OF TYMPANOSTOMY TUBES IN CHILDREN IN THE UNITED-STATES, 1988 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID OTITIS-MEDIA; SURGERY; LIFE AB Information from the 1988 National Health Interview Survey Medical Device Implant Supplement was used to obtain the first population estimates of the prevalence of implanted tympanostomy tubes, a common treatment for otitis media. The prevalence rate was estimated to be 13 per 1000 children aged younger than 18 years. Statistically significant differences in prevalence were found for sex (boys, 15/1000; girls, 10/1000), race (Whites, 15/1000; others, 4/1000), and activity level (''limited,'' 44/1000; others, 11/1000). Thirty percent of the tubes were replacements; infection was the reason for 75% of the original implants. The morbidity and costs associated with tympanostomy tubes are of public health importance. RP BRIGHT, RA (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,5600 FISHERS LANE,HFZ-161,ROCKVILLE,MD 20857, USA. RI Bright, Roselie/D-2240-2016 NR 12 TC 25 Z9 25 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1993 VL 83 IS 7 BP 1026 EP 1028 DI 10.2105/AJPH.83.7.1026 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LN036 UT WOS:A1993LN03600021 PM 8328599 ER PT J AU MOORE, RM BRIGHT, RA JENG, LL SHARKNESS, CM HAMBURGER, SE HAMILTON, PM AF MOORE, RM BRIGHT, RA JENG, LL SHARKNESS, CM HAMBURGER, SE HAMILTON, PM TI THE PREVALENCE OF INTERNAL ORTHOPEDIC FIXATION DEVICES IN CHILDREN IN THE UNITED-STATES, 1988 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID INJURIES AB This study provides the first estimated prevalence of implanted orthopedic fixation devices (e.g., pins or wires) among children in the United States, based on the Medical Device Implant Supplement to the 1988 National Health Interview Survey. The overall prevalence was 27 per 10 000 children younger than 18 years; prevalence was highest (59/10 000) among those aged 12 to 17 years. The lower extremities were the most frequent body site (43%) and injury was the leading specific reason for implantation (37%). Some (10%) were replacement implants. C1 US FDA,CTR DEVICES & RADIOL HLTH,5600 FISHERS LANE,HFZ-161,ROCKVILLE,MD 20857. RI Bright, Roselie/D-2240-2016 NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1993 VL 83 IS 7 BP 1028 EP 1030 DI 10.2105/AJPH.83.7.1028 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LN036 UT WOS:A1993LN03600022 PM 8328600 ER PT J AU YAO, GQ GRILL, S EGAN, W CHENG, YC AF YAO, GQ GRILL, S EGAN, W CHENG, YC TI POTENT INHIBITION OF EPSTEIN-BARR-VIRUS BY PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES WITHOUT SEQUENCE SPECIFICATION SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; DNA-POLYMERASE; TYPE-2 GROWTH; REPLICATION; CELLS; ANALOGS AB We found that 28-mer phosphorothioate oligodeoxynucleotides (S-oligos) with and without sequence specificity complementary to Epstein-Barr virus (EBV) genes are potent inhibitors of EBV replication in cell culture. The decrease in the amount of EBV DNA, the activity of intracellular viral DNA polymerase, and virus production were dose dependent, with a 90% inhibitory dose of approximately 0.5 muM. No inhibition of cell growth was observed with the S-oligos at concentrations up to 20 muM. The mechanism of action appears to be the inhibition of EBV DNA synthesis. The reversibility of anti-EBV action is dependent on the dose and duration of drug exposure. S-oligos should be considered a new class of anti-EBV agents. C1 YALE UNIV,SCH MED,DEPT PHARMACOL,333 CEDAR ST,NEW HAVEN,CT 06510. US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-44358] NR 27 TC 24 Z9 24 U1 0 U2 1 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 JUL PY 1993 VL 37 IS 7 BP 1420 EP 1425 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LL214 UT WOS:A1993LL21400007 PM 8395789 ER PT J AU SUTHERLAND, JB FU, PP YANG, SK VONTUNGELN, LS CASILLAS, RP CROW, SA CERNIGLIA, CE AF SUTHERLAND, JB FU, PP YANG, SK VONTUNGELN, LS CASILLAS, RP CROW, SA CERNIGLIA, CE TI ENANTIOMERIC COMPOSITION OF THE TRANS-DIHYDRODIOLS PRODUCED FROM PHENANTHRENE BY FUNGI SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; STEREOSELECTIVE METABOLISM; PHANEROCHAETE-CHRYSOSPORIUM; ABSOLUTE-CONFIGURATION; CUNNINGHAMELLA-ELEGANS; LIQUID-CHROMATOGRAPHY; RESOLUTION AB The trans-dihydrodiols produced during the metabolism of phenanthrene by Cunninghamella elegans, Syncephalastrum racemosum, and Phanerochaete chrysosporium were purified by high-performance liquid chromatography (HPLC). The enantiomeric compositions and optical purities of the trans-dihydrodiols were determined to compare interspecific differences in the regio- and stereoselectivity of the fungal enzymes. Circular dichroism spectra of the trans-dihydrodiols were obtained, and the enantiomeric composition of each preparation was analyzed by HPLC with a chiral stationary-phase column. The phenanthrene trans-1,2-dihydrodiol produced by C. elegans was a mixture of the IR,2R and IS,2S enantiomers in variable proportions. The phenanthrene trans-3,4-dihydrodiol produced by P. chrysosporium was the optically pure 3R,4R enantiomer, but that produced by S. racemosum was a 68:32 mixture of the 3R,4R and 3S,4S enantiomers. The phenanthrene trans-9,10-dihydrodiol produced by P. chrysosporium was predominantly the 9S,10S enantiomer, but those produced by C. elegans and S. racemosum were predominantly the 9R,10R enantiomer. The results indicate that although different fungi may exhibit similar regioselectivity, there still may be differences in stereoselectivity that depend on the species and the cultural conditions. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,BETHESDA,MD 20814. GEORGIA STATE UNIV,DEPT BIOL,ATLANTA,GA 30303. NR 30 TC 20 Z9 21 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 1993 VL 59 IS 7 BP 2145 EP 2149 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA LL310 UT WOS:A1993LL31000023 PM 16348991 ER PT J AU GROSSMAN, LW FAALAND, RW AF GROSSMAN, LW FAALAND, RW TI MINIMUM RESOLUTION SPECIFICATION OF INTRAOCULAR-LENS IMPLANTS USING THE MODULATION TRANSFER-FUNCTION SO APPLIED OPTICS LA English DT Article DE INTRAOCULAR LENS; INTRAOCULAR LENS TESTING; OPTICAL QUALITY; IMAGE QUALITY; RESOLUTION; MODULATION TRANSFER FUNCTION ID OPTICAL-QUALITY; EYES AB We investigated the use of modulation transfer function (MTF) measurements to provide a standard test of minimum optical quality of intraocular lenses. We used a water cell with plane entrance and exit windows. This geometry is independent of lens material but relatively simple to implement. We investigated the choice of aperture stop, and 3.0 mm was deemed a suitable choice of stop diameter. Minimum acceptable performance must be specified if this technique is to be adopted as a standard method. The MTF of an ideal lens defocused 1/2 wave is suggested as a possible reference. Strehl ratios, although desirable because they can be measured directly without determining MTF's, were found to be unsuitable. These ratios tend to emphasize the high-frequency response, and the observed ratios are typically too low to provide assurance that the low-frequency response is as high as desired. MTF integrals or contrast at spatial frequencies of particular interest were found to be useful benchmarks of acceptable optical quality. RP US FDA, CTR DEVICES & RADIOL HLTH, HFZ-134, ROCKVILLE, MD 20857 USA. NR 17 TC 7 Z9 7 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD JUL 1 PY 1993 VL 32 IS 19 BP 3497 EP 3503 PG 7 WC Optics SC Optics GA LK405 UT WOS:A1993LK40500023 PM 20829973 ER PT J AU ISHIGATSUBO, Y IGARASHI, T OHNO, S UEDA, A OKUBO, T KLINMAN, DM AF ISHIGATSUBO, Y IGARASHI, T OHNO, S UEDA, A OKUBO, T KLINMAN, DM TI CROSS-REACTIVITY OF IGM-SECRETING AND IGG-SECRETING B-CELLS IN AUTOIMMUNE MICE SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; AUTOANTIBODIES; ANTIBODIES; ANTIGENS; QUANTITATION AB Objective. To determine the frequency with which in vivo-activated B cells secrete cross-reactive antibodies in lupus-prone mice. Methods. Analysis of freshly isolated splenic lymphocytes by chamber enzyme-linked immunospot assay. Results. Young New Zealand black, New Zealand black x New Zealand white, and MRL/lpr mice expressed repertoires in which 16-20% of IgM-secreting cells and 0-2% of IgG-secreting cells were cross-reactive. By comparison, 21-31% of IgM- and 4-14% of IgG-secreting cells in adult animals with active lupus were cross-reactive (P < 0.01). Conclusion. Cross-reactive B cells constitute an abnormally large proportion of the repertoire expressed in mice with active autoimmune disease. C1 US FDA,CTR BIOLOG EVALUAT & RES,DIV VIROL,BETHESDA,MD 20205. RP ISHIGATSUBO, Y (reprint author), YOKOHAMA CITY UNIV,SCH MED,DEPT INTERNAL MED,FUKUURA 3-9,KANAZAWA KU,YOKOHAMA 236,JAPAN. NR 15 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1993 VL 36 IS 7 BP 1003 EP 1006 DI 10.1002/art.1780360718 PG 4 WC Rheumatology SC Rheumatology GA LM080 UT WOS:A1993LM08000017 PM 8318027 ER PT J AU CHATFIELD, MR AF CHATFIELD, MR TI THE DIRECTORY OF FOOD AND NUTRITION INFORMATION, 2ND EDITION - FRANK,RC, IRVING,HB SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Book Review RP CHATFIELD, MR (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JUL PY 1993 VL 81 IS 3 BP 342 EP 343 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA LL859 UT WOS:A1993LL85900023 ER PT J AU CROSS, DR MILLER, BJ JAMES, SJ AF CROSS, DR MILLER, BJ JAMES, SJ TI A SIMPLIFIED HPLC METHOD FOR SIMULTANEOUSLY QUANTIFYING RIBONUCLEOTIDES AND DEOXYRIBONUCLEOTIDES IN CELL-EXTRACTS OR FROZEN TISSUES SO CELL PROLIFERATION LA English DT Article ID DNA STRAND BREAKS; LIQUID-CHROMATOGRAPHY; QUANTITATIVE-DETERMINATION; TRIPHOSPHATE POOLS; DEOXYADENOSINE; METHOTREXATE; LYMPHOCYTES; NUCLEOTIDES; MODULATION; INDUCTION AB Agents and conditions that induce alterations in deoxyribonucleotide pools can have important regulatory effects on the rate of DNA synthesis as well as cell cycle progression. A simplified procedure for the separation of both ribonucleoside triphosphates (NTP) and deoxyribonucleoside triphosphates (dNTP) is presented which utilizes reversed phase high-performance liquid chromatography coupled with diode array detection. The simultaneous resolution of NTP and dNTP peaks within the same cell extract effectively eliminates the need for post-extraction steps such as periodate oxidation and/or boronate affinity chromatography previously used to degrade or isolate co-eluting NTP from dNTP. The resolution of two nucleotides, dGTP and ADP, was found empirically to vary with the efficiency of the C18 column. High efficiency columns (>90 000 plates/m) provided good separation; however, less efficient columns resulted in co-elution of dGTP and ADP. These co-eluting nucleotides can be accurately quantified, if necessary, using diode array technology and a mathematical expression which incorporates molar peak coefficients and peak areas obtained by monitoring at dual wavelengths. Tissue samples or single cell suspensions were extracted with trichloroacetic acid and the neutralized extract was injected directly into the column without prior lyophilization. The per cent recovery of standards was greater-than-or-equal-to 99% and replicate extractions within or between samples were highly reproducible (SD<5%). The single step method described minimizes potential losses associated with post-extraction manipulation and provides the capability to examine alterations in nucleotide precursor-product metabolism under various physiological and pharmacological conditions. C1 US FDA,NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079. NR 21 TC 32 Z9 32 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7722 J9 CELL PROLIFERAT JI Cell Prolif. PD JUL PY 1993 VL 26 IS 4 BP 327 EP 336 DI 10.1111/j.1365-2184.1993.tb00328.x PG 10 WC Cell Biology SC Cell Biology GA LQ820 UT WOS:A1993LQ82000003 PM 8343561 ER PT J AU VANDERVEEN, JE AF VANDERVEEN, JE TI FATS AND OILS SO CEREAL FOODS WORLD LA English DT Editorial Material RP VANDERVEEN, JE (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, 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 JUL PY 1993 VL 38 IS 7 BP 523 EP 523 PG 1 WC Food Science & Technology SC Food Science & Technology GA LP063 UT WOS:A1993LP06300010 ER PT J AU SWENSON, DH ELBAYOUMY, K SHUIE, GH HECHT, SS FIALA, E KADLUBAR, FF FREEMAN, JP AF SWENSON, DH ELBAYOUMY, K SHUIE, GH HECHT, SS FIALA, E KADLUBAR, FF FREEMAN, JP TI SYNTHESIS OF N-(PURIN-8-YL)ARYLAMINES SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID DEOXYNUCLEOSIDE ADDUCTS; DNA; GUANINE; INVITRO; CARCINOGENESIS; ATOMS; C-8 AB Methods for direct synthesis of N-(purin-8-yl)arylamines were investigated. N-(Purin-8-yl)arylamines are adducts from reaction of electrophilic metabolites of arylamines with DNA and have not been readily available by direct synthesis. Ability to generate significant quantities of this class of DNA adduct by synthetic means would facilitate basic research in molecular toxicology. Two routes with common thiourea intermediates were developed for this purpose. In the first route, 6-hydroxy-2,4,5-triaminopyrimidine was caused to react in aqueous medium with dithiocarbamate derivatives of o-, m-, or p- toluidine to form corresponding 2,4-diamino-5-(tolylthioureido)aminopyrimidin-6-ones in 60-70% yields. The thiourea intermediates were converted to carbodiimides and isolated in 20-25% yields after treatment with HgO in dimethylformamide. The carbodiimides were cyclized at 125-degrees-C in dimethylformamide under N2 for 45 h to yield N-(guanin-8-yl)(o-, m-, or p-)toluidines in 65-75% yields. In the second route, direct reaction of p-tolyl isothiocyanate with 6-hydroxy-2,4,5-triaminopyrimidine or with 4,5,6-triaminopyrimidine in dimethylformamide and triethylamine led to the formation of 2,4-diamino-5-(p-tolylthioureido)aminopyrimidin-6-one and 4,6-diamino-5-(tolylthioureido)aminopyrimidine, respectively, in 77-79% yields. Methylation of the two thiourea derivatives by methyl iodide in dimethylformamide gave the corresponding methylisothiuronium derivatives, which were isolated in 71% and 84% yields (as HI salts), respectively. Conversion of the methylisothiuronium derivatives to N-(guanin-8-yl)-p-toluidine or N-(adenin-8-yl)-p-toluidine was accomplished by heating in dimethylformamide for 5-7 h at 80-90-degrees-C, in 70% and 62% yields, respectively. The most efficient synthesis of the thioureas would appear to proceed by coupling the triaminopyrimidine precursor with the easily prepared dithiocarbamate derivatives of the arylamine followed by conversion to a methylisothiuronium and thermal cyclization of the methylated intermediate. These routes should be directly applicable to polynuclear arylamines and suitably blocked diaminoarenes. C1 KARKINOS BIOCHEM INC,CHANDLER,AZ 85225. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. AMER HLTH FDN,VALHALLA,NY 10595. RP SWENSON, DH (reprint author), LOUISIANA STATE UNIV,SCH VET MED,BATON ROUGE,LA 70803, USA. OI Hecht, Stephen/0000-0001-7228-1356 FU NCI NIH HHS [1 R43CA34954-01]; NCPDCID CDC HHS [NCI 35519]; NIEHS NIH HHS [ES03257] NR 27 TC 4 Z9 4 U1 0 U2 0 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 JUL-AUG PY 1993 VL 6 IS 4 BP 480 EP 485 DI 10.1021/tx00034a014 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA LM738 UT WOS:A1993LM73800014 PM 8374045 ER PT J AU FURUHAMA, K BENSON, RW KNOWLES, BJ ROBERTS, DW AF FURUHAMA, K BENSON, RW KNOWLES, BJ ROBERTS, DW TI IMMUNOTOXICITY OF CEPHALOSPORINS IN MICE SO CHEMOTHERAPY LA English DT Article DE CEPHALOSPORINS; IMMUNE RESPONSE; SPLENOMEGALY; MICE ID IMMUNE-RESPONSE AB This study was performed in female B6C3F1 mice to confirm previously observed effects of selected cephalosporin antibiotics on nonspecific immunity, and to determine possible effects on specific acquired immunity and host resistance. Mice were treated intravenously with DQ-2556, ceftizoxime or ceftezole at 800 mg/kg/day for 3, 5, or 7 consecutive days. All three compounds increased total serum IgM levels from day 3, but had no effects on total serum IgG levels and the thymus weight. All three cephalosporin antibiotics caused a slight increase in spleen weight and splenic germinal centers were enlarged after 5- or 7-day treatments. Antibody responses to type III pneumococcal polysaccharide (S3), a T-cell-independent immunogen, and sheep red blood cells (SRBC), a T-cell-dependent immunogen, were slightly decreased after 5-day dosings with each compound, and reached significance in DQ-2556 (response to S3) and ceftizoxime (response to S3 and SRBC). None of the tested cephalosporin antibiotics altered delayed-type hypersensitivity to oxazolone or host resistance to Plasmodium yoelii, indicating that the antibiotic-treated mice retained the capacity to mount a multicomponent and sustained protective immune response. These data suggest that although cephalosporins may cause polyclonal expansion of B cells with associated increases in total serum IgM, they do not affect the tested measures of cell-mediated immunity or host resistance. The decreased IgM antibody responses to S3 and SRBC are associated with but not known to be causally related to the concurrent IgM hypergammaglobulinemia. C1 NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,DIV TOXICOL,LITTLE ROCK,AR 72205. NR 17 TC 4 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0009-3157 J9 CHEMOTHERAPY JI Chemotherapy PD JUL-AUG PY 1993 VL 39 IS 4 BP 278 EP 285 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA LK036 UT WOS:A1993LK03600008 PM 8325130 ER PT J AU MATTHEWS, EJ AF MATTHEWS, EJ TI TRANSFORMATION OF BALB/C-3T3 CELLS .1. INVESTIGATION OF EXPERIMENTAL PARAMETERS THAT INFLUENCE DETECTION OF SPONTANEOUS TRANSFORMATION SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID HAMSTER EMBRYO CELLS; CHEMICAL CARCINOGENS; MALIGNANT TRANSFORMATION; FOCUS FORMATION; 10T1/2 CELLS; 3T3 CELLS; ASSAY; INDUCTION; BALB/3T3; SYSTEM AB The frequency of spontaneous morphological transformation is an important variable in measuring chemical-induced transformation in BALB/c-3T3 clone A-31-1-13 cell cultures. Data from 110 experiments, which included benzo[a]pyrene control groups and other chemical treatment group were analyzed for factors that influenced spontaneous transformation. Spontaneous transformants demonstrated a continuum of morphological variants (type I, II, and III foci) that fit a normal distribution if converted to log10. The magnitude of transformation depended on the ampule of cryopreserved cells and the serum lot. Although the average frequency was approximately 0.71 x 10(-6) (type III foci/cell that survived and proliferated to confluence), the absolute number of foci/vessel increased in proportion to the surface area of the culture vessel. Thus, the frequency of spontaneous transformation was directly related to the cumulative number of mitoses that occurred in forming the contact-inhibited monolayer. These data are consistent with a hypothesis that spontaneous transformation in BALB/c-3T3 cells is a mutational event or some other single-step phenomenon. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. FU NIEHS NIH HHS [N01-ES-65150] NR 44 TC 10 Z9 11 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 277 EP 291 DI 10.2307/3431401 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400034 PM 8243398 ER PT J AU MATTHEWS, EJ AF MATTHEWS, EJ TI TRANSFORMATION OF BALB/C-3T3 CELLS .2. INVESTIGATION OF EXPERIMENTAL PARAMETERS THAT INFLUENCE DETECTION OF BENZO[A]PYRENE-INDUCED TRANSFORMATION SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID GENE-TOX PROGRAM; CHEMICAL CARCINOGENS; EMBRYO CELLS; MUTAGENICITY; BALB/3T3; RODENTS; SYSTEM; ASSAY AB Benzo[a]pyrene (BaP) induced significant morphological transformation of clone A31-1-13 BALB/c-3T3 cells without exogenous activation. Therefore, BaP was selected as a model to determine the internal consistency of detection of chemical-induced transformation. BaP induced a continuum of type I-III foci of different sizes, and the ratio of type I-III to type III foci/vessel was usually about 2-fold. The major finding was that BaP induced highly significant transformation responses, and the magnitude of these responses were inversely correlated with the cytotoxicity of the treatment doses. Thus, the induction of BaP-induced transformation behaved as though it was caused by a mutational event. Variability among responses were shown to depend on the serum lot and the cryopreserved ampule of cells. In addition, experiments with low spontaneous transformation responses had an impaired ability to detect BaP; however, experiments with high or normal spontaneous responses had a normal ability to detect BaP. Because the expression of BaP-induced transformation depended on both the cytotoxicity of the treatment and the cumulative number of mitoses, the frequency of BaP-induced transformation should be reported as the number of foci/vessel, but not expressed as the number of foci/viable cell surviving the chemical treatment. These conclusions are important because the same 110 experiments described in this report were also used to evaluate the transformation responses of many different carcinogenic and noncarcinogenic chemicals. These data are being reported separately. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. FU NIEHS NIH HHS [NIEHS NO1-ES-65150] NR 35 TC 11 Z9 12 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 293 EP 310 DI 10.2307/3431402 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400035 PM 8243399 ER PT J AU MATTHEWS, EJ AF MATTHEWS, EJ TI TRANSFORMATION OF BALB/C-3T3 CELLS .3. DEVELOPMENT OF A COCULTURE CLONAL SURVIVAL ASSAY FOR QUANTIFICATION OF CHEMICAL CYTOTOXICITY IN HIGH-DENSITY CELL-CULTURES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID INTERCELLULAR COMMUNICATION; EMBRYO CELLS; CARCINOGENS; BALB/3T3 AB A co-culture clonal survival assay was developed to measure the cytotoxicity of test chemical treatments to BALB/c-3T3 cells because the standard clonal survival assay using 200 wild type (WT) cells frequently overestimates chemical cytotoxicity when compared with identical treatment doses in high-density cultures. The assay used co-cultures of 3.2 x 10(4) WT cells, the same seeding density used in the transformation assay, and 200 ouabain resistant (OUA(r)) cells. After a 48-hr test chemical treatment, co-cultured cells were fed with culture medium containing 4 mM ouabain. The test chemical was cytotoxic to an equal percentage of WT and OUA(r) cells. Ouabain treatments killed the remaining WT cells. Thus, OUA(r) cells surviving the test chemical treatment measured the relative cloning efficiency (RCE) of all treated cells in the high-density cell co-culture. The co-culture assay succeeded because metabolic cooperation at the OUA(r) locus was not detected in BALB/c-3T3 cells. Five chemicals induced comparable cytotoxic responses in both assays, including actinomycin D, 5-bromo-2'-deoxyuridine, N'-methyl-N-nitro-N'-nitrosoguanidine, dimethyl sulfoxide and sodium chloride. In contrast, chemical cytotoxic responses detected in the standard and co-culture assays differed by greater-than-or-equal-to 10-fold for 11-aminoundecanoic acid, benzo[a]pyrene, cytosine arabinoside, and 3-methylcholanthrene and differed by >2-fold for 2-acetylaminofluorene and dimethylnitrosamine. Detection of 11-aminoundecanoic acid-induced transformation was shown to be dependent on selecting treatment doses from the co-culture assay data. Thus, this method permits more accurate assessment of both chemical-induced cytotoxicity and transformation. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. FU NIEHS NIH HHS [N01-ES-65150] NR 25 TC 9 Z9 9 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 311 EP 318 DI 10.2307/3431403 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400036 PM 8243400 ER PT J AU MATTHEWS, EJ SPALDING, JW TENNANT, RW AF MATTHEWS, EJ SPALDING, JW TENNANT, RW TI TRANSFORMATION OF BALB/C-3T3 CELLS .4. RANK-ORDERED POTENCY OF 24 CHEMICAL RESPONSES DETECTED IN A SENSITIVE NEW ASSAY PROCEDURE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID EMBRYO CELLS; CARCINOGENICITY; MUTAGENICITY; SALMONELLA; BALB/3T3; RODENTS; PROGRAM AB This report introduces an improved method of detecting chemical-induced morphological transformation of A-31-1-13 BALB/c-3T3 cells. The new procedure uses an increased target cell population to assess chemical-induced damage by increasing the initial seeding density and by delaying the initiation time of chemical treatment. Furthermore, a newly developed co-culture clonal survival assay was used to select chemical doses for the transformation assay. This assay measured the relative cloning efficiency (RCE) of chemical treatments in high-density cell cultures. In addition, transformation assay sensitivity was enhanced through the use of improved methods to solubilize many chemicals. From a group of 24 chemicals tested in at least two trials, clear evidence of chemical-induced transformation was detected for 12 chemicals (aphidicolin, barium chloride-2H2O, 5-bromo-2'-deoxyuridine, C.I. direct blue 15, trans-cinnamaldehyde, cytosine arabinoside, diphenylnitrosamine, manganese sulfate-H2O, 2-mereaptobenzimidazole, mezerein, riddelliine, and 2,6-xylidine); 2 chemicals had equivocal activity [C.I. direct blue 218 and mono(2-ethylhexyl)phthalatel, 9 chemicals were inactive [carisoprodol, chloramphenicol sodium succinate, 4-chloro-2-nitroaniline, C.I. acid red 114, isobutyraldehyde, mono(2-ethylhexyl)adipate, sodium fluoride, and 12-O-tetradecanoylphorbol-13-acetate), and 1 chemical had an indeterminate response (2,6-dinitrotoluene). All positive responses were detected in the absence of an exogenous activation system and exhibited significant activity at two or more consecutive doses. This report also presents a mathematical method that uses t-statistics for rank-ordering the potency of chemical-induced transformation responses. This model detects sensitivity differences in experiments used to evaluate chemical-induced transformation. Furthermore, it provides a method to estimate a chemical's transformation response in terms of the historical behavior of the assay, as well as its future activity. The most active of the 24 chemicals was mezerein, and the least active chemical was diphenylnitrosamine. C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. FU NIEHS NIH HHS [N01-ES-65150] NR 29 TC 22 Z9 22 U1 1 U2 4 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 319 EP 345 DI 10.2307/3431404 PG 27 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400037 PM 8243401 ER PT J AU MATTHEWS, EJ SPALDING, JW TENNANT, RW AF MATTHEWS, EJ SPALDING, JW TENNANT, RW TI TRANSFORMATION OF BALB/C-3T3 CELLS .5. TRANSFORMATION RESPONSES OF 168 CHEMICALS COMPARED WITH MUTAGENICITY IN SALMONELLA AND CARCINOGENICITY IN RODENT BIOASSAYS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID EMBRYO CELLS; TOXICITY; BALB/3T3; PROGRAM; SYSTEM; ASSAY AB This report describes the activities of 168 chemicals tested in a standard transformation assay using A-31-1-13 BALB/c-3T3 cells. The data set includes 84 carcinogens, 77 noncarcinogens, and 7 research chemicals. Carcinogens included 49 mutagens and 35 nonmutagens; noncarcinogens included 24 mutagens and 53 nonmutagens. The transformation assay did not use an exogenous activation system, thus, all chemical responses depended on the inherent target cell metabolic capacity where metabolic activation was required. The upper dose limit was 100 milli-osmolar because the assay could not discriminate active and inactive chemicals tested above this concentration. Certain physicochemical properties resulted in technical problems that affected chemical biological activity. For example, chemicals that reacted with plastic were usually nonmutagenic carcinogens. Similarly, chemicals that were insoluble in medium, or bound metals, were usually nonmutagenic and nontransforming. Multifactorial data analyses revealed that the transformation assay discriminated between nonmutagenic carcinogens and noncarcinogens; it detected 64% of the carcinogens and only 26% of the noncarcinogens. In contrast, the transformation assay detected most mutagenic chemicals, including 94% of the mutagenic carcinogens and 70% of the mutagenic noncarcinogens. Thus, transformation or Salmonella typuimurium mutagenicity assays could not discriminate mutagenic carcinogens from mutagenic noncarcinogens. Data analyses also revealed that mutagenic chemicals were more cytotoxic than nonmutagenic chemicals; 88% of the mutagens had an LD50 < 5 mM, whereas half of the nonmutagens had an LD50 > 5 mM. Binary data analyses of the same data set revealed that the transformation assay and rodent bioassay had a concordance of 71%, a sensitivity for carcinogens of 80.0%, and a specificity for detecting noncarcinogens of 60%. In contrast, Salmonella mutagenicity assays and rodent bioassays had a concordance of 63%, a sensitivity of 58%, and a specificity of 69%. The transformation assay complemented the Salmonella mutagenesis assay in the identification of nonmutagenic carcinogens; thus, the two assays had a combined 83% sensitivity for all carcinogens and a 75% specificity for nonmutagenic noncarcinogens. C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. FU NIEHS NIH HHS [N01-ES-65150] NR 26 TC 75 Z9 77 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 347 EP 482 DI 10.2307/3431405 PG 136 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400038 PM 8243403 ER PT J AU BLOCK, C RAZ, R FRASCH, CE EPHROS, M GREIF, Z TALMON, Y ROSIN, D BOGOKOWSKY, B AF BLOCK, C RAZ, R FRASCH, CE EPHROS, M GREIF, Z TALMON, Y ROSIN, D BOGOKOWSKY, B TI REEMERGENCE OF MENINGOCOCCAL CARRIAGE ON 3-YEAR FOLLOW-UP OF A KIBBUTZ POPULATION AFTER WHOLE-COMMUNITY CHEMOPROPHYLAXIS SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article AB A long-term study was conducted to determine the rate of re-emergence of throat carriage of meningococci in a semi-closed kibbutz community after the administration of chemoprophylaxis to all its members. Serotype B:4 was selected as marker organism since it was isolated from a fatal case and was the most frequently occurring strain (80 %) among serogroup B isolates, which themselves comprised 54 % of all meningococci. The carriage rate among Israeli residents (volunteer workers were analyzed separately) before treatment was 6.6 % (49/748) overall, with 4.3 % group B strains. Three weeks after treatment, in most cases with rifampicin (whereby three persistently positive persons were retreated with minocycline), no meningococci were recovered. Six months later, 1.9 % of a population sample aged less-than-or-equal-to 30 years were positive, while before treatment and one and three years later, 9.4 %, 8.6 % and 4.6 % respectively were positive in this age group. Serotype B:4 comprised 81.3 % of group B strains before prophylaxis, 5.3 % after one year, and 28.6 % after three years, thus possibly re-establishing itself as the single dominant serotype. The marked suppression of carriage after mass chemoprophylaxis appeared to last at least six months, with the meningococcal population being re-established within a year. C1 CHAIM SHEBA MED CTR,NATL CTR MENINGOCOCCI,IL-52621 TEL HASHOMER,ISRAEL. CENT HOSP EMEK,INFECT DIS UNIT,AFULA,ISRAEL. US FDA,BACTERIAL POLYSACCHARIDES LAB,BETHESDA,MD 20014. NAHARIYA HOSP,DEPT PEDIAT,NAHARIYYA,ISRAEL. CARMEL HOSP,DEPT PEDIAT,HAIFA,ISRAEL. NAHARIYA HOSP,DEPT OTOLARYNGOL,NAHARIYYA,ISRAEL. RP BLOCK, C (reprint author), CHAIM SHEBA MED CTR,DEPT CLIN MICROBIOL,IL-52621 TEL HASHOMER,ISRAEL. NR 11 TC 8 Z9 8 U1 0 U2 0 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD JUL PY 1993 VL 12 IS 7 BP 505 EP 511 DI 10.1007/BF01970955 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA LR092 UT WOS:A1993LR09200002 PM 8404910 ER PT J AU AKAHANE, K PLUZNIK, DH AF AKAHANE, K PLUZNIK, DH TI INTERFERON-GAMMA DESTABILIZES INTERLEUKIN-1-INDUCED GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR MESSENGER-RNA IN MURINE VASCULAR ENDOTHELIAL-CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE GM-CSF; INTERFERON-GAMMA; DOWN-REGULATION; MESSENGER-RNA; DESTABILIZATION; ENDOTHELIAL CELLS ID MESSENGER-RNA STABILIZATION; FACTOR GENE-EXPRESSION; GM-CSF; POSTTRANSCRIPTIONAL REGULATION; LYMPHOCYTES-T; RELEASE; REGION; LINE AB Vascular endothelial cells can affect hematopoiesis by releasing granulocyte-macrophage colony-stimulating factor (GM-CSF). In the present study, we show that GM-CSF production in murine aorta-derived vascular endothelial cells is regulated by two cytokines: interleukin-1 (IL-1), which induces the production of GM-CSF, and interferon gamma (IFN-gamma), which downregulates this production. The GM-CSF gene is constitutively transcribed in these cells and the transcription rate of the GM-CSF gene does not change with either IL-1 alone or IL-1 plus IFN-gamma. Whereas IL-1 treatment increases the GM-CSF mRNA half-life, simultaneous treatment with IL-1 plus IFN-gamma results in a decrease in the mRNA half-life. IL-1 also enhances IL-6 mRNA accumulation in these cells, although by increasing its transcription rate. In this case, IFN-gamma does not affect IL-6 mRNA expression. These data suggest that IL-1-induced GM-CSF expression in endothelial cells is regulated at the posttranscriptional level and that IFN-gamma specifically inhibits GM-CSF expression via destabilization of the mRNA. These suppressive effects of IFN-gamma provide evidence for an additional role of IFN-gamma in regulating GM-CSF production. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 33 TC 16 Z9 16 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1993 VL 21 IS 7 BP 878 EP 884 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW612 UT WOS:A1993MW61200010 PM 8319780 ER PT J AU REID, MJ LOCKEY, RF TURKELTAUB, PC PLATTSMILLS, TAE AF REID, MJ LOCKEY, RF TURKELTAUB, PC PLATTSMILLS, TAE TI SURVEY OF FATALITIES FROM SKIN TESTING AND IMMUNOTHERAPY 1985-1989 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE SKIN TESTING; IMMUNOTHERAPY; ASTHMA; ANAPHYLAXIS ID DERMATOPHAGOIDES-PTERONYSSINUS EXTRACT; SYSTEMIC REACTIONS; HYMENOPTERA VENOM; SAFETY AB Background: The Committee on Allergen Standardization of the American Academy of Allergy and Immunology (AAAI) began a study of fatalities associated with skin testing and immunotherapy in an effort to identify risk factors and to ascertain whether any additional precautions are required to prevent and treat serious reactions. Methods: Questionnaire data was obtained from members of the AAAI and the American College of Allergy and Immunology, regarding 17 fatalities associated with immunotherapy for the years 1985 to 1989. In this period, no fatalities were reported with skin testing. The mean age of patients who died was 36.0 years (range: 10 to 77 years), and 69% were female. Of the patients who died, 76% had asthma, and most were reported to have had factors associated with severity (i.e., lability, required steroids, and/or prior hospitalizations). The only patient who had rhinitis alone had cardiovascular disease and was receiving a beta-blocker High sensitivity by skin test or RAST was reported by 71%, and 36% reported prior systemic reactions. Sixty-five percent of the patients were undergoing build-up therapy. Fatalities involved use of allergen doses between 1:1 million to 1:10 wt/vol. Other factors associated with fatalities were: changing to a new vial of extract, 5; dosing error or inappropriate dose adjustment, 5; allergen season, 5; symptomatic before injection, 4; not waiting after injection, 2; and home injection, 1. Onset of anaphylaxis occurred within 20 minutes in eleven patients, within 20 to 30 minutes in one, and after more than 30 minutes in one. In eleven cases the cause of death was associated with respiratory compromise. These data reinforce the need for special precautions in treating high-risk patients with asthma. The annual fatality rate from administration of allergenic extracts in the United States remains very low: 1 fatality per 2 million doses, but additional educational efforts to further reduce the fatality rate are needed. C1 ALLERGY & IMMUNOL MED ASSOCIATES,SAN FRANCISCO,CA. JAMES A HALEY VET HOSP,TAMPA,FL. US FDA,CTR BIOL EVALUAT & RES,ALLERGY & IMMUNOCHEM LAB,BETHESDA,MD 20014. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. UNIV S FLORIDA,TAMPA,FL 33620. FU PHS HHS [A1-20565] NR 31 TC 217 Z9 228 U1 1 U2 8 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 JUL PY 1993 VL 92 IS 1 BP 6 EP 15 DI 10.1016/0091-6749(93)90030-J PN 1 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA LQ353 UT WOS:A1993LQ35300002 PM 8335856 ER PT J AU HOLLAND, DC MUNNS, RK ROYBAL, JE HURLBUT, JA LONG, AR AF HOLLAND, DC MUNNS, RK ROYBAL, JE HURLBUT, JA LONG, AR TI SIMULTANEOUS DETERMINATION OF XYLAZINE AND ITS MAJOR METABOLITE, 2,6-DIMETHYLANILINE, IN BOVINE AND SWINE KIDNEY BY LIQUID-CHROMATOGRAPHY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TRANQUILIZERS; CONFIRMATION; EXTRACTION; CARAZOLOL; RESIDUES; URINE AB A liquid chromatographic (LC) method is described for the simultaneous determination of xylazine (XY) and its major metabolite, 2,6-dimethylaniline (2,6-DMA), in bovine and swine kidney in the 25-100 ppb range. XY and 2,6-DMA are extracted from kidney with chloroform, followed by cleanup on an acidic Celite 545 column. A muBondapak phenyl column is used for LC separation with UV determination at 225 nm. The mobile phase is a mixture of acetonitrile, water, sodium acetate, and acetic acid. Mean recoveries from bovine kidney were 78.3% for XY, with a standard deviation (SD) of 7.45 and a coefficient of variation (CV) of 9.51%, and 87.2% for 2,6-DMA, with an SD of 8.38 and a CV of 9.61 %. Mean recoveries from swine kidney were 80.8% for XY, with an SD of 5.92 and a CV of 7.33%, and 86.7% for 2,6-DMA, with an SD of 6.16 and a CV of 7.10%. RP HOLLAND, DC (reprint author), US FDA,ANIM DRUGS RES CTR,DENVER FED CTR,POB 25087,DENVER,CO 80225, USA. NR 12 TC 12 Z9 12 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1993 VL 76 IS 4 BP 720 EP 724 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA LR821 UT WOS:A1993LR82100004 PM 8374321 ER PT J AU WEBER, JD SMEDLEY, MD AF WEBER, JD SMEDLEY, MD TI LIQUID-CHROMATOGRAPHIC METHOD FOR DETERMINATION OF SULFAMETHAZINE RESIDUES IN MILK - COLLABORATIVE STUDY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FOODS AB Seven laboratories participated in a collaborative study of a liquid chromatographic (LC) method for determination of sulfamethazine (SMZ) residues in raw milk that were previously frozen. The milk is extracted with chloroform, the chloroform is evaporated, and the residue is suspended in hexane and extracted with 0.1M KH2PO4 (PDP) solution. The PDP extract is analyzed by LC on a C18 column with methanol-0.1M PDP (30 + 70) as mobile phase. Individual laboratories were instructed to analyze 5 replicates each of control milk, fortified control milk at 2 levels, and 3 blind samples. Blind samples included raw milk fortified with SMZ at 10 and 20 ppb and 1 sample containing SMZ residue from a dosed cow. For blind fortified samples containing 10 ppb SMZ, average recovery and relative standard deviations for repeatability and reproducibility (RSD(r) and RSR(R)) based on the results from 6 of the 7 participating laboratories were 8.21 ppb, 7.16%, and 23.16%, respectively. Similar data, including results from a seventh participant who reported instrumental problems but was not eliminated by the Dixon outlier test, were 9.13 ppb, 8.38%, and 31.94%, respectively. These results demonstrate that the method is suitable for the determination of SMZ residues in milk at 10 ppb and above. The method was adopted first action by AOAC International. C1 US FDA,CTR VET MED,DIV VET MED RES,BELTSVILLE AGR RES CTR E,BLDG 328A,BELTSVILLE,MD 20705. NR 5 TC 7 Z9 7 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 1993 VL 76 IS 4 BP 725 EP 729 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA LR821 UT WOS:A1993LR82100005 PM 8374322 ER PT J AU LIEBERMAN, R AF LIEBERMAN, R TI FK506, ARTIFICIAL-INTELLIGENCE AND PHARMACOECONOMICS SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID IMMUNOSUPPRESSION; TRANSPLANTATION; CYCLOSPORINE; FK-506; TRIAL RP LIEBERMAN, R (reprint author), US FDA,CTR DRUG EVALUAT & RES,PARKLAWN BLDG ROOM 9B-04,ROCKVILLE,MD 20857, USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUL PY 1993 VL 33 IS 7 BP 596 EP 598 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LN457 UT WOS:A1993LN45700003 PM 7690045 ER PT J AU MCMICHAEL, J LIEBERMAN, R DOYLE, H MCCAULEY, J FUNG, J STARZL, TE AF MCMICHAEL, J LIEBERMAN, R DOYLE, H MCCAULEY, J FUNG, J STARZL, TE TI AN INTELLIGENT AND COST-EFFECTIVE COMPUTER DOSING SYSTEM FOR INDIVIDUALIZING FK506 THERAPY IN TRANSPLANTATION AND AUTOIMMUNE DISORDERS SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID LIVER-TRANSPLANTATION; FK-506 THERAPY; CYCLOSPORINE; OPTIMIZATION; STRATEGY; KIDNEY AB The accuracy and precision of an intelligent dosing system (IDS) for FK506 in predicting doses to achieve target drug levels has been prospectively evaluated in transplant and autoimmune patients. For dose individualization, the knowledge base is updated with patient-specific feedback including the current dose, drug level, and the new target level. The study population of 147 patients consisted of 97 transplant patients (liver and kidney) and a 50 patients with autoimmune disorders. Patients in the transplant study group were entered sequentially and followed as a cohort. Patients in the autoimmune study group were randomly assigned to one of three predefined FK506 concentration windows (low, -.1-.3; medium, 0.4-.7; and high, 0.8-1.3 ng/mL) as part of a concentration controlled clinical trial. Predictions of steady-state plasma drug levels were made throughout the clinical course of autoimmune patients and during the first 6 weeks post-transplant in liver and kidney recipients. FK506 concentration in plasma was measured by a monoclonal antibody based ELISA assay. Accuracy was computed as the mean prediction error (mpe). Precision was computed as the root mean squared prediction error (rmspe). The accuracy of the IDS in each study group was as follows: 0.016 ng/mL (liver), -0.034 ng/mL (kidney), and -0.022 ng/mL (autoimmune). Because the 95% confidence interval included zero in each case, the IDS showed no bias. The precision of the IDS in each study group was as follows: 0.133 ng mL (liver), 0.1903 ng/mL (kidney), and 0.1188 ng/mL (autoimmune). These results indicate that the FK506 IDS is both accurate and very precise (reproducible) in transplant and autoimmune patients. The performance of the FK506 compares favorably with previously reported pharmacokinetic dosing methods such as population nomograms and adaptive control feedback methods (least-squares and Bayesian). Based on our findings, this IDS should have a number of important uses relevant to the drug development process, the prescribing physician and the individual patient. It provides an efficient method for implementing concentration controlled clinical trials. It should accelerate the physician's learning curve while at the same time help to maximize therapeutic drug efficient and minimize toxicity with drugs exhibiting nonlinear kinetics and narrow therapeutic indices. Preliminary studies suggest that these assets result in a significant cost-benefit advantage by reducing the duration of hospitalization. Current studies are in progress to validate this and carefully measure its pharmacoeconomic impact. C1 US FDA,COLL STAFF,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857. RP MCMICHAEL, J (reprint author), UNIV PITTSBURGH,INST TRANSPLANTAT,3601 5TH AVE,5W FALK CLIN,PITTSBURGH,PA 15213, USA. RI Fung, John/A-2679-2012 FU NIDDK NIH HHS [R01 DK029961-19] NR 20 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUL PY 1993 VL 33 IS 7 BP 599 EP 605 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LN457 UT WOS:A1993LN45700004 PM 7690046 ER PT J AU JONES, RA MATHESON, JC AF JONES, RA MATHESON, JC TI RELATIONSHIP BETWEEN SAFETY DATA AND BIOCONTAINMENT DESIGN IN THE ENVIRONMENTAL ASSESSMENT OF FERMENTATION ORGANISMS - AN FDA PERSPECTIVE SO JOURNAL OF INDUSTRIAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; RECOMBINANT DNA; WASTE-WATER; SOIL; STRAINS; PBR322 AB The Center for Veterinary Medicine requires strain/construct-specific data for recombinant fermentation organisms used in the production of animal drugs and feed additives. Fermentation plant biocontainment schemes are chosen based, in part, upon the ability of the organism to survive and persist in the environment and to transfer genetic information to indigenous organisms. Survival and persistence study methods may include one of the following ecosystems: activated sludge, mammalian gut, soil or river water. Gene transfer protocols can be incorporated into a persistence study. These studies are designed to show that the recombinant construct behaves similarly to the host in a representative ecosystem where the organism could be introduced inadvertently. The studies need to provide repeatable results and reflect current state-of-art design and methods. Data verification is conducted by FDA investigators during Good Laboratory Practice inspections. Biocontainment guidelines, such as those developed by the NIH Recombinant DNA Advisory Committee, set general biocontainment goals for large groupings of recombinant organisms. The FDA, as required under the National Environmental Policy Act, must base its decision making on verifiable scientific data specific to each application. Therefore, in addition to using these guidelines as benchmarks, sponsors are required to submit strain/construct-specific data to support the selection of an appropriate biocontainment level. Once additional well-controlled studies for a variety of constructs are available, broader generalizations as to biocontainment may be drawn. RP JONES, RA (reprint author), US FDA,CVM HFV-150,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 23 TC 1 Z9 1 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0169-4146 J9 J IND MICROBIOL JI J. Indust. Microbiol. PD JUL PY 1993 VL 11 IS 4 BP 217 EP 222 DI 10.1007/BF01569594 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA LP274 UT WOS:A1993LP27400003 PM 7763893 ER PT J AU HERNANDEZ, JF KASPAR, CW HARTMAN, PA COLWELL, RR AF HERNANDEZ, JF KASPAR, CW HARTMAN, PA COLWELL, RR TI MICROTITRATION PLATE MOST-PROBABLE-NUMBER TESTS FOR THE ENUMERATION OF ESCHERICHIA-COLI IN ESTUARINE AND MARINE WATERS SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE ESCHERICHIA-COLI; MOST-PROBABLE-NUMBER; 4-METHYLUMBELLIFERYL-BETA-D-GLUCURONIDE (MUG) ID FLUOROGENIC METHOD; STANDARD METHODS; SEA-WATER; IDENTIFICATION; MUG; COLIFORMS; BACTERIA; SAMPLES; QUALITY; ASSAYS AB Microtitration plate most-probable-number tests were developed for the estimation of Escherichia coli numbers in estuarine and marine waters. A 32-well test was adequate for testing most waters, although the entire plate could be used for each dilution in waters containing low numbers of E. coli. The incorporation of 4-methylumbelliferyl-beta-D-glucuronide into modified A-1 broth facilitated the identification of E. coli. Values obtained by using microtitration plate most-probable-number tests correlated with those obtained by using standard 3- and 5-tube most-probable-number tests, but were more precise and reproducible. C1 INST PASTEUR,SERV EAUX & ENVIRONM,LILLE,FRANCE. USFDA,FISHERY RES BRANCH,DAUPHIN ISL,AL 36528. IOWA STATE UNIV SCI & TECHNOL,DEPT MICROBIOL IMMUNOL & PREVENT MED,AMES,IA 50011. UNIV MARYLAND,DEPT MICROBIOL,COLL PK,MD 20742. UNIV MARYLAND,CTR MARINE BIOTECHNOL,BALTIMORE,MD 21202. NR 29 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JUL PY 1993 VL 18 IS 1 BP 11 EP 19 DI 10.1016/0167-7012(93)90067-R PG 9 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA LP289 UT WOS:A1993LP28900002 ER PT J AU CEJKA, Z GOULDKOSTKA, J BURNS, D KESSEL, M AF CEJKA, Z GOULDKOSTKA, J BURNS, D KESSEL, M TI LOCALIZATION OF THE BINDING-SITE OF AN ANTIBODY AFFECTING ATPASE ACTIVITY OF CHAPERONIN CPN60 FROM BORDETELLA-PERTUSSIS SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID ELECTRON-MICROSCOPY; PROTEIN; GROEL C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MEMBRANE & ULTRASTRUCT RES,IL-91010 JERUSALEM,ISRAEL. MAX PLANCK INST BIOCHEM,W-8033 MARTINSRIED,GERMANY. US FDA,DIV BACTERIAL PROD,BETHESDA,MD 20892. UNIV MARYLAND,DEPT MICROBIOL,COLL PK,MD 20742. NR 20 TC 4 Z9 4 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JUL-AUG PY 1993 VL 111 IS 1 BP 34 EP 38 DI 10.1006/jsbi.1993.1033 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ME928 UT WOS:A1993ME92800005 PM 7902725 ER PT J AU IGARASHI, K DAVID, M LARNER, AC FINBLOOM, DS AF IGARASHI, K DAVID, M LARNER, AC FINBLOOM, DS TI IN-VITRO ACTIVATION OF A TRANSCRIPTION FACTOR BY GAMMA-INTERFERON REQUIRES A MEMBRANE-ASSOCIATED TYROSINE KINASE AND IS MIMICKED BY VANADATE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHATASE-ACTIVITY; FC-RECEPTORS; PROTEIN; PHOSPHORYLATION; CELLS; IGG AB Gamma interferon (IFN-gamma) activates the formation of a DNA-binding protein complex (FcRFgamma) that recognizes the gamma response region (GRR) of the promoter for the human high-affinity Fcgamma receptor. In a membrane-enriched fraction prepared from human peripheral blood monocytes, IFN-gamma activation of FcRFgamma occurred within 1 min and was ATP dependent. Activation of FcRFgamma required a tyrosine kinase activity, and recognition of the GRR sequence by FcRFgamma could be abrogated by treatment with a tyrosine-specific protein phosphatase. Treatment of cells with vanadate alone resulted in the formation of FcRFgamma without the need for IFN-gamma. UV cross-linking and antibody competition experiments demonstrated that the FcRFgamma complex was composed of at least two components: the 91-kDa protein of the IFN-alpha-induced transcription complex ISGF3 and a 43-kDa component that bound directly to the GRR. Therefore, specificity for IFN-induced transcriptional activation of early response genes requires at least two events: (i) ligand-induced activation of membrane-associated protein by tyrosine phosphorylation and (ii) formation of a complex composed of an activated membrane protein(s) and a sequence-specific DNA-binding component. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 29 TC 97 Z9 97 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1993 VL 13 IS 7 BP 3984 EP 3989 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200015 PM 8321205 ER PT J AU MORRIS, SM AF MORRIS, SM TI THE GENETIC TOXICOLOGY OF 5-FLUOROPYRIMIDINES AND 5-CHLOROURACIL SO MUTATION RESEARCH LA English DT Review DE 5-FLUOROPYRIMIDINES; 5-CHLOROURACIL; 5-FLUOROURACIL; 5-FLUORODEOXYURIDINE; 5-CHLORODEOXYURIDINE ID SISTER-CHROMATID EXCHANGE; HUMAN-COLON ADENOCARCINOMA; NOVIKOFF HEPATOMA-CELLS; HAMSTER OVARY CELLS; RESISTANT KB CELLS; DNA-STRAND BREAKS; MOUSE FM3A CELLS; DIHYDROFOLATE-REDUCTASE RNA; SYNTHASE-NEGATIVE MUTANTS; LYMPHOMA S-49 CELLS AB The halogenated pyrimidines were synthesized in the 1950s as potential anti-tumor agents after the discovery that certain tumors preferentially incorporated uracil rather than thymine into the DNA. The fluorinated derivatives are widely recognized today as effective treatment modalities, especially with tumors of the head, neck and breast. Mechanistically, efficacy of the fluorinated pyrimidines results from the ability of these compounds to incoporporate into RNA and inhibit its maturation to those forms necessary for cellular metabolism and from the inhibition of the enzyme, thymidylate synthetase, which controls the biosynthesis of thymine and DNA synthesis. The 5-fluoropyrimidines can incorporate into DNA, but the contribution of this phenomenon to the overall efficacy of this class of chemotherapeutic agents is not totally resolved. Evidence exists that this class of compounds possesses the properties to induce genotoxic effects, both in bacterial and eukaryotic cells. Most notably, these effects include the induction of cellular toxicity and the induction of chromosome aberrations. The biology and chemistry of the chlorinated pyrimidines were first explored as a possible means of sensitizing the DNA to ionizing radiation in a manner similar to the sensitization observed when DNA incorporates bromodeoxyuridine. This approach was not utilized clinically. The genetic toxicology of this compound became important with the discovery of the ribonucleoside in the effluents of sewage treatment plants. Evidence is now available that the chlorinated pyrimidines, upon conversion to deoxyribonucleosides, are effective mutagens, clastogens and toxicants, as well as extremely effective inducers of sister-chromatid exchanges. RP MORRIS, SM (reprint author), US PHS,US FDA,NATL CTR TOXICOL RES,DIV GENET TOXICOL,HFT 120,1 NCTR DR,JEFFERSON,AR 72079, USA. NR 132 TC 58 Z9 58 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL PY 1993 VL 297 IS 1 BP 39 EP 51 DI 10.1016/0165-1110(93)90006-9 PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LK294 UT WOS:A1993LK29400002 PM 7686272 ER PT J AU MEYER, MC STRAUGHN, AB JARVI, EJ WOOD, GC VASHI, VI HEPP, P HUNT, J AF MEYER, MC STRAUGHN, AB JARVI, EJ WOOD, GC VASHI, VI HEPP, P HUNT, J TI THE EFFECT OF GASTRIC PH ON THE ABSORPTION OF CONTROLLED-RELEASE THEOPHYLLINE DOSAGE FORMS IN HUMANS SO PHARMACEUTICAL RESEARCH LA English DT Article DE CONTROLLED-RELEASE THEOPHYLLINE; PH-DEPENDENT DISSOLUTION; ACHLORHYDRIC HUMANS; BIOAVAILABILITY ID TABLETS; INVIVO; DOGS AB The bioavailability of three marketed controlled-release dosage forms and a reference solution of theophylline was studied in eight subjects with normal gastric fluid acidity and seven subjects who were achlorhydric. Gastric pH was monitored with a Heidelberg capsule. One of the controlled-release dosage forms dissolved more rapidly in vitro when exposed to acid conditions, one dissolved more rapidly in pH 7.5 media, and the third dissolved at a rate independent of pH. Using a crossover design, each subject received each dosage form twice. Blood was sampled for up to 47 hr after each dose, and serum was assayed for theophylline by HPLC. The product which dissolved more rapidly under acid conditions in vitro exhibited a 3 hr longer T(max) in the achlorhydrics compared to the normal subjects. The product which dissolved more rapidly in the pH 7.5 media exhibited a relatively higher AUC(0-infinity) in the achlorhydric subjects than in normal subjects after the AUC data were normalized for clearance differences between the two subject groups. The in vivo bioavailability of these dosage forms could be related to the in vitro dissolution characteristics for some parameters. However, with the exception of the mean T(max) values, the mean bioavailability parameters differed by less than 20% between the two subject groups. C1 US FDA,DIV BIOPHARMACEUT,ROCKVILLE,MD 20857. RP MEYER, MC (reprint author), UNIV TENNESSEE CTR HLTH SCI,COLL PHARM,DEPT PHARMACEUT,MEMPHIS,TN 38163, USA. FU NCRR NIH HHS [RR00211] NR 19 TC 6 Z9 6 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUL PY 1993 VL 10 IS 7 BP 1037 EP 1045 DI 10.1023/A:1018923008579 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA LM886 UT WOS:A1993LM88600017 PM 8378245 ER PT J AU BRANHAM, WS ZEHR, DR SHEEHAN, DM AF BRANHAM, WS ZEHR, DR SHEEHAN, DM TI DIFFERENTIAL SENSITIVITY OF RAT UTERINE GROWTH AND EPITHELIUM HYPERTROPHY TO ESTROGENS AND ANTIESTROGENS SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID REPRODUCTIVE-TRACT ABNORMALITIES; BREAST-CANCER PATIENTS; CLOMIPHENE CITRATE; VAGINAL EPITHELIUM; TAMOXIFEN; UTERUS; CARCINOMA; ESTRADIOL; BINDING; OVULATION AB Triphenylethylene antiestrogens are considered weak estrogen agonists based on their limited ability to induce estrogen responses, in particular uterine growth. We compared the uterotrophic activity of naturally occurring and synthetic estrogens with that of antiestrogens by quantitating uterine wet weight and hypertrophy in the uterine luminal and glandular epithelium. Immature rats received five daily injections of either an estrogen (17beta-estradiol [E2], diethylstilbestrol [DES], or ethynyl estradiol [EE]) or an antiestrogen (tamoxifen [TAM], monohydroxytamoxifen [OH-TAM], or clomiphene citrate [CC]) (0.001-100 mug/rat/day) subcutaneously in sesame oil and were sacrificed approximately 2 hr after the last injection. Both DES and EE increased uterine weight at doses between 0.01-100 mug/rat/day; E2 was about 10-fold less potent. The antiestrogens increased uterine weight only slightly. DES, EE, and the three antiestrogens each increased luminal epithelium hypertrophy to over 3-fold above that in controls. While the potencies of these synthetic compounds differed (DES = EE > OH-TAM > TAM = CC), each hypertrophic response occurred over two log doses, and the response curves displayed identical slopes. E2, however, required a range of four log doses to achieve the same degree of luminal epithelium hypertrophy. The three antiestrogens elicited glandular epithelium hypertrophy up to 2-fold above controls at the same doses that induced luminal epithelium hypertrophy; the order of potency was OH-TAM > TAM = CC. However, the three estrogens increased glandular epithelium hypertrophy only marginally. Thus, under dosing conditions commonly used to assess uterotrophic activity, these ''antiestrogens'' are complete, albeit less potent, estrogen agonists in the luminal epithelium and, unlike estrogens, induce hypertrophy in the glandular epithelium. C1 UNIV CENT ARKANSAS,DEPT BIOL,CONWAY,AR 72032. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM,LITTLE ROCK,AR 72201. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL,LITTLE ROCK,AR 72201. RP BRANHAM, WS (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,JEFFERSON,AR 72079, USA. NR 37 TC 54 Z9 55 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUL PY 1993 VL 203 IS 3 BP 297 EP 303 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LJ223 UT WOS:A1993LJ22300005 PM 8516342 ER PT J AU MOREHOUSE, KM KU, Y AF MOREHOUSE, KM KU, Y TI IDENTIFICATION OF IRRADIATED FOODS BY MONITORING RADIOLYTICALLY PRODUCED HYDROCARBONS SO RADIATION PHYSICS AND CHEMISTRY LA English DT Article; Proceedings Paper CT 8TH INTERNATIONAL MEETING ON RADIATION PROCESSING CY SEP 13-18, 1992 CL BEIJING, PEOPLES R CHINA DE GAS CHROMATOGRAPHY; GAMMA-IRRADIATION; HYDROCARBONS; SEAFOOD; MEAT PRODUCTS ID RADIOLYSIS PRODUCTS; PARAMETERS AB Many countries allow the treatment of foods with low doses of ionizing radiation to reduce microbial and insect infestations, inhibit maturation, and extend shelf life. Therefore, a reliable method is needed to identify irradiated foods and to determine their compliance with respect to allowable absorbed radiation dose. several approaches for the identification of irradiated foods have been developed such as measurement of radiolytic products, chemiluminescence, and thermoluminescence, and the use of electron spin resonance spectroscopv to measure free radicals trapped in bone. A method for the determination of radiolytically produced hydrocarbons was developed in our laboratory to evaluate the utility of monitoring these compounds as indicators of food irradiation. The method involves the extraction of the radiolytic hydrocarbons from foods and their quantitation by gas chromatography. Concentrations of the radiolytically produced hydrocarbons increased linearly with radiation doses ranging from 0 to 6 kGy. The limit of detection appears to be approximately 1 kGy. The method was found to be useful for the identification of gamma-irradiated foods such as shrimp, frog legs, pork, beef, and poultry. Results of the method evaluation studies of these food matrices as well as factors affecting hydrocarbon production and determination will be presented. RP MOREHOUSE, KM (reprint author), US FDA,DIV FOOD CHEM & TECHNOL,200 C ST SW,WASHINGTON,DC 20204, USA. NR 18 TC 8 Z9 8 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0146-5724 J9 RADIAT PHYS CHEM JI Radiat. Phys. Chem. PD JUL-SEP PY 1993 VL 42 IS 1-3 BP 359 EP 362 DI 10.1016/0969-806X(93)90266-W PG 4 WC Chemistry, Physical; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical SC Chemistry; Nuclear Science & Technology; Physics GA LK323 UT WOS:A1993LK32300076 ER PT J AU JOHNSON, GC AF JOHNSON, GC TI NEED FOR CAUTION DURING MR-IMAGING OF PATIENTS WITH ANEURYSM CLIPS SO RADIOLOGY LA English DT Letter RP JOHNSON, GC (reprint author), US FDA, CTR DEVICES & RADIOL HLTH, OFF HLTH AFFAIRS, 1390 PICCARD DR, ROCKVILLE, MD 20850 USA. NR 2 TC 19 Z9 19 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1993 VL 188 IS 1 BP 287 EP 288 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LH284 UT WOS:A1993LH28400058 PM 8511314 ER PT J AU GALLETTI, GC REEVES, JB FRANCIS, BA REEVES, VB AF GALLETTI, GC REEVES, JB FRANCIS, BA REEVES, VB TI ION-TRAP AND QUADRUPOLE MASS-SPECTRA OF LIGNIN PYROLYSATES - HOW WELL DO THEY COMPARE SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article; Proceedings Paper CT 11TH INFORMAL MEETING ON MASS SPECTROMETRY CY 1993 CL BUDAPEST, HUNGARY ID WHEAT STRAW; SPECTROMETRY AB Lignin samples from wheat straw, orchard grass, red clover and a synthetic lignin were subjected to pyrolysis gas chromatography/mass spectrometry using both quadrupole (QMS) and ion-trap detector (ITD). ITD mass spectra were comparable with those presented in the National Bureau of Standards (NBS) library and with those obtained by QMS as evaluated by discrepancy factors. Computer-assisted library searches for ITD spectra were successful for 22 of 47 compounds. The other 25 compounds were not present in the library. A typical program and mass spectra are shown. Statistical data are discussed. C1 USDA,RUMINANT NUTR LAB,BELTSVILLE,MD 20705. US FDA,CTR VET MED,BELTSVILLE,MD 20705. NR 20 TC 9 Z9 9 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD JUL PY 1993 VL 7 IS 7 BP 641 EP 645 DI 10.1002/rcm.1290070717 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA LN526 UT WOS:A1993LN52600016 PM 8347868 ER PT J AU EDIGER, MN PETTIT, GH WEIBLINGER, RP AF EDIGER, MN PETTIT, GH WEIBLINGER, RP TI NONINVASIVE MONITORING OF EXCIMER-LASER ABLATION BY TIME-RESOLVED REFLECTOMETRY SO REFRACTIVE AND CORNEAL SURGERY LA English DT Article AB BACKGROUND: Current excimer laser photorefractive procedures use empiric etch rates to determine specific changes in corneal shape. A real-time analytic method for monitoring the tissue ablation process may be useful in tailoring energy delivery to a specific patient and in detecting detrimental phenomena such as corneal desiccation. METHODS: We monitored excimer laser ablation by studying the amplitude and temporal characteristics of ArF laser pulses reflected from the ablation site. Two target materials were used: polymethylmethacrylate (PMMA, a synthetic polymer that undergoes an incubation phase where no ablation occurs for an initial finite number of laser pulses), and bovine cornea. Observed reflectivity changes during irradiation of PMMA were compared to profilometric ablation depth measurements. Corneal ablation Was performed both with and without nitrogen gas flow at the ablation site to study the effect of tissue desiccation. RESULTS: For ablation of PMMA at 160 mJ/cm2, the incubation phase included the initial eight laser pulses. For corneal tissue ablation at a fluence of 125 mJ/cm2, flowing nitrogen gas caused significant shortening and amplitude reduction in the reflected laser signals. CONCLUSIONS: Noninvasive time-resolved reflectometry provided real-time information about target ablation. This technique may have diagnostic utility during laser corneal surgical procedures. RP EDIGER, MN (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,1901 CHAPMAN AVE,HF2-134,ROCKVILLE,MD 20857, USA. NR 0 TC 10 Z9 10 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0883-0444 J9 REFRACT CORNEAL SURG PD JUL-AUG PY 1993 VL 9 IS 4 BP 268 EP 275 PG 8 WC Ophthalmology SC Ophthalmology GA LZ327 UT WOS:A1993LZ32700006 PM 8398972 ER PT J AU ZIEGLER, MH GRAFTON, TF HANSEN, DK AF ZIEGLER, MH GRAFTON, TF HANSEN, DK TI THE EFFECT OF TOLBUTAMIDE ON RAT EMBRYONIC-DEVELOPMENT INVITRO SO TERATOLOGY LA English DT Article ID MOUSE EMBRYOS; CONGENITAL-MALFORMATIONS; GLUTATHIONE DEPLETION; HYPOGLYCEMIC DRUGS; EMBRYOTOXICITY; EXPOSURE; CULTURE; SYSTEM; ASSAY AB Tolbutamide (TOLB) is a sulfonylurea used to treat non-insulin-dependent diabetes mellitus and is a suspected teratogen. However, it is not possible to discriminate between potential teratogenic effects of TOLB and malformations produced by either drug-induced hypoglycemia or the diabetic state itself. We examined the direct effect of TOLB on rat embryos cultured in a rodent whole embryo culture system. CD strain rat embryos were cultured for 48 h beginning on day 9 of gestation (plug day = day 0). Tolbutamide was added at various concentrations (90-3,600 muM). At the end of culture, viable embryos were examined for morphological score, number of somite pairs, crown-rump and head lengths, and DNA and protein content. Tolbutamide produced dose-related decreases in all endpoints at concentrations (2,250-3,600 muM) which are two to four times the human therapeutic concentration. Sera from TOLB-treated rats were adjusted to contain equal concentrations of glucose and insulin and then used for embryo culture. Serum from TOLB-treated rats had no observable effect on embryonic development. The mechanism for the embryotoxic effect of TOLB is unknown; however, the drug was previously demonstrated to alter activity of purified yeast glutathione reductase (GR). Because GR may be important for normal embryonic development, the effect of TOLB on this enzyme activity in cultured rat embryos was evaluated. Tolbutamide (2,700 muM) reduced embryonic GR activity by 35-57%. These results indicate that TOLB has a direct embryotoxic effect at levels 2 to 4 times the usual therapeutic serum concentrations on developing rodent embryos which may be mediated by GR inhibition. C1 NATL CTR TOXICOL RES,FOOD & DRUG ADM,DEPT HLTH & HUMAN SERV,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. NR 44 TC 13 Z9 13 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 0040-3709 J9 TERATOLOGY JI Teratology PD JUL PY 1993 VL 48 IS 1 BP 45 EP 51 DI 10.1002/tera.1420480108 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA LH937 UT WOS:A1993LH93700007 PM 8351647 ER PT J AU COLLINS, TFX BLACK, TN RUGGLES, DI AF COLLINS, TFX BLACK, TN RUGGLES, DI TI TERATOGENIC POTENTIAL OF FD-AND-C RED NO-3 WHEN GIVEN BY GAVAGE SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE ERYTHROSINE; GAVAGE; RATS; TERATOGENIC POTENTIAL ID ERYTHROSINE; RATS AB FD&C Red No. 3 (erythrosine) is a commonly used food additive. As part of a series of studies on the potential fetal developmental effects of food colors, FD&C Red No. 3 was administered by gavage to pregnant Osborne-Mendel rats at daily dose levels of 15, 30, 100, 200, 400, or 800 mg/kg on days 0-19 of gestation. Control animals were given distilled water by gavage. On gestation day 20, the animals were euthanized and cesarean sections were performed. During the entire treatment period, feed consumption by the animals given 400 mg/kg doses was increased significantly; the increases in the animals given 30 or 800 mg/kg were of borderline significance. The only significant increase in maternal weight gain, on days 0-7 in the animals given 30 mg/kg, was considered a random occurrence. No dose-related changes were seen in maternal clinical findings, implantations, fetal viability, or fetal size (weight and length). No fetal terata were seen, and neither skeletal nor visceral development was affected. FD&C Red No. 3 was neither fetotoxic nor teratogenic at 800 mg/kg when given by gavage. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NR 14 TC 5 Z9 6 U1 0 U2 1 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-AUG PY 1993 VL 9 IS 4 BP 605 EP 616 PG 12 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA MD216 UT WOS:A1993MD21600003 PM 8296313 ER PT J AU RAZZAQUE, A WILLIAMS, O WANG, JH RHIM, JS AF RAZZAQUE, A WILLIAMS, O WANG, JH RHIM, JS TI NEOPLASTIC TRANSFORMATION OF IMMORTALIZED HUMAN EPIDERMAL-KERATINOCYTES BY 2 HHV-6 DNA CLONES SO VIROLOGY LA English DT Article ID VIRUS HUMAN HERPESVIRUS-6; TYPE-1 REPLICATION; IDENTIFICATION; INFECTION; HEPATITIS; SEQUENCES; LYMPHOMA; INVITRO; TROPISM; GENOME C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP RAZZAQUE, A (reprint author), US FDA,CBER,DNA VIRUS RES LAB,DIV VIRAL PROD,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 45 Z9 47 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 JUL PY 1993 VL 195 IS 1 BP 113 EP 120 DI 10.1006/viro.1993.1351 PG 8 WC Virology SC Virology GA LH710 UT WOS:A1993LH71000012 PM 8391179 ER PT J AU KEASLER, SP HALL, RH AF KEASLER, SP HALL, RH TI DETECTING AND BIOTYPING VIBRIO-CHOLERAE-O1 WITH MULTIPLEX POLYMERASE CHAIN-REACTION SO LANCET LA English DT Letter ID VIBRIO-CHOLERAE RP KEASLER, SP (reprint author), CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 3 TC 180 Z9 195 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUN 26 PY 1993 VL 341 IS 8861 BP 1661 EP 1661 DI 10.1016/0140-6736(93)90792-F PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LJ727 UT WOS:A1993LJ72700038 PM 8100020 ER PT J AU BLACK, PL MCKINNON, KM WOODEN, SL USSERY, MA AF BLACK, PL MCKINNON, KM WOODEN, SL USSERY, MA TI ANTIVIRAL ACTIVITY OF A SYNTHETIC DOUBLE-STRANDED POLYRIBONUCLEOTIDE INTERFERON INDUCER IN A MURINE AIDS RETROVIRUS MODEL - ROLE OF AUGMENTATION OF NATURAL-KILLER-CELL ACTIVITY AND SYNERGY WITH ORAL AZT SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; INFECTIONS; MICE C1 SO RES INST,FREDERICK RES CTR,FREDERICK,MD 21701. RP BLACK, PL (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857, USA. RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU NIAID NIH HHS [NIAID (1U01AI2567)] NR 6 TC 3 Z9 3 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD JUN 23 PY 1993 VL 685 BP 467 EP 470 DI 10.1111/j.1749-6632.1993.tb35908.x PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LL567 UT WOS:A1993LL56700061 PM 8363255 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI PROPOSED CALL FOR SCIENTIFIC-DATA ON INFLATABLE PENILE IMPLANTS 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 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 16 PY 1993 VL 269 IS 23 BP 2964 EP 2964 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LF941 UT WOS:A1993LF94100006 PM 8501827 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI FDA WARNS HEARING-AID MANUFACTURERS TO AVOID MISLEADING ADVERTISING CLAIMS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 16 PY 1993 VL 269 IS 23 BP 2964 EP 2964 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LF941 UT WOS:A1993LF94100005 PM 8501827 ER PT J AU WEINTRAUB, M AF WEINTRAUB, M TI CHANGING OVER-THE-COUNTER DRUGS WHILE RETAINING THE BRAND-NAME - RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP WEINTRAUB, M (reprint author), CTR DRUG EVALUAT & RES,OFF OTC DRUG EVALUAT,WASHINGTON,DC, USA. NR 0 TC 1 Z9 1 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 15 PY 1993 VL 118 IS 12 BP 988 EP 988 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LF937 UT WOS:A1993LF93700024 ER PT J AU SAHU, SC GRAY, GC AF SAHU, SC GRAY, GC TI INTERACTIONS OF FLAVONOIDS, TRACE-METALS, AND OXYGEN - NUCLEAR-DNA DAMAGE AND LIPID-PEROXIDATION INDUCED BY MYRICETIN SO CANCER LETTERS LA English DT Article DE MYRICETIN; ANTIOXIDANTS; FLAVONOIDS; DNA DAMAGE; LIPID PEROXIDATION; OXYGEN RADICALS ID SUPEROXIDE-DISMUTASE; HYDROGEN-PEROXIDE; CIGARETTE-SMOKE; QUERCETIN; RADICALS; ANTIOXIDANTS; ANTICARCINOGENS; CARCINOGENESIS; ANTIMUTAGENS; GENERATION AB The extent of DNA damage and lipid peroxidation induced by myricetin, a polyphenolic flavonoid, were studied in isolated rat liver nuclei under aerobic conditions. Myricetin induced significant (P < 0.05) concentration-dependent nuclear DNA degradation concurrent with lipid peroxidation; these effects were enhanced by iron (III) or copper (II). Catalase, superoxide dismutase (SOD), mannitol and sodium azide did not inhibit myricetin-induced nuclear DNA damage in the presence of iron (III) or copper (II). However, all of these antioxidants stimulated myricetin-induced DNA damage in the presence of copper (II). Lipid peroxidation induced by myricetin was significantly inhibited only by SOD in the presence of copper (II), whereas it was enhanced by catalase and sodium azide in the presence of iron (III). These results demonstrate the pro-oxidant properties of polyphenolic flavonoids, which are generally considered to be antioxidants and anticarcinogens, and suggest a dual role for these flavonoids in mutagenesis and carcinogenesis. RP SAHU, SC (reprint author), US FDA,DIV TOXICOL RES,MUIRKIRK RD,LAUREL,MD 20708, USA. NR 33 TC 62 Z9 64 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 15 PY 1993 VL 70 IS 1-2 BP 73 EP 79 DI 10.1016/0304-3835(93)90077-M PG 7 WC Oncology SC Oncology GA LM257 UT WOS:A1993LM25700011 PM 8330305 ER PT J AU HU, RQ GAN, YX LIU, JL MILLER, D ZOON, KC AF HU, RQ GAN, YX LIU, JL MILLER, D ZOON, KC TI EVIDENCE FOR MULTIPLE BINDING-SITES FOR SEVERAL COMPONENTS OF HUMAN LYMPHOBLASTOID INTERFERON-ALPHA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I-125-LABELED MOUSE INTERFERON; CELL-SURFACE RECEPTOR; HIGH-AFFINITY BINDING; COMMON RECEPTORS; GAMMA; EXPRESSION; BETA AB The antiproliferative and competitive binding activities of 20 purified components of human lymphoblastoid interferon (IFN)-alpha were compared with that of recombinant human IFN-alpha2b on Daudi and AU937 cells. We observed broad ranges of antiproliferative activities of the IFN-alpha components on these cell lines. Daudi cells were more sensitive to the IFN-alpha components than AU937 cells; the concentrations of the components that resulted in 50% inhibition of cell growth ranged from 0.003 ng/ml to >10 ng/ml on Daudi cells and 0.05 ng/ml to >200 ng/ml on AU937 cells. Component o was the most active human IFN-alpha on both cell lines. Scatchard analysis demonstrated that the number of IFN-alpha2b binding sites is greater on Daudi cells (12,700 binding sites/cell) than AU937 cells (3,300 binding sites/cell); however, their receptor affinities were similar. Component o, which exhibited high antiproliferative activity on both cell lines, had low affinity for the IFN-alpha2b binding site on AU937 and Daudi cells. Several human IFN-alphas (components b', b'', and e) appeared to have high affinity binding sites but low antiproliferative activity on both Daudi and AU937 cells. These data suggest that there may be more than one binding site or receptor for human IFN-alpha, and/or there may be a multicomponent receptor involved in the biological actions of these molecules. C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BLDG 29,RM 130,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. NR 33 TC 47 Z9 47 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 JUN 15 PY 1993 VL 268 IS 17 BP 12591 EP 12595 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LG658 UT WOS:A1993LG65800055 PM 8509399 ER PT J AU EPSTEIN, SL MISPLON, JA LAWSON, CM SUBBARAO, EK CONNORS, M MURPHY, BR AF EPSTEIN, SL MISPLON, JA LAWSON, CM SUBBARAO, EK CONNORS, M MURPHY, BR TI BETA-2-MICROGLOBULIN-DEFICIENT MICE CAN BE PROTECTED AGAINST INFLUENZA-A INFECTION BY VACCINATION WITH VACCINIA-INFLUENZA RECOMBINANTS EXPRESSING HEMAGGLUTININ AND NEURAMINIDASE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8+ T-CELLS; VIRUS-INFECTION; LYMPHOCYTIC CHORIOMENINGITIS; NUCLEOPROTEIN; IMMUNITY; PROTEINS; RECOVERY; ANTIGENS; INVIVO; IMMUNIZATION AB Immunity to viral infections includes both antibody and T cell components. The contributions of humoral and cell-mediated immune responses vary depending on virus and host factors. We have used an in vivo challenge system to examine protective immunity to influenza A(H1N1) virus infection in immunocompetent B6 (H-2b) mice, and in H-2b mice homozygous for disruption of the gene for beta2-microglobulin, termed beta2mu(-/-) mice. The latter mice do not express conventional MHC class I complexes on cell surfaces and lack CD8+ class I-restricted T cells. Ten vaccinia virus recombinants, each expressing 1 of the 10 proteins of influenza virus, were used to immunize the mice. Normal mice were protected against challenge with influenza virus by vaccination with HA-VAC and NA-VAC, but not by any of the vaccinia vectors expressing one of the eight other influenza virus proteins nor by a mixture of all eight of the latter vectors. Similar results were observed in mice of H-2d or H-2k MHC haplotypes. The beta2mu(-/-) mice were also protected by immunization with HA-VAC and NA-VAC, demonstrating that classical CD8+ CTL responses were not required for protection. Depletion of CD4+ T cells in either normal or beta2mu(-/-) mice at the time of challenge had little or no effect on protection induced by HA-VAC or NA-VAC, suggesting that preformed antibody is the dominant mediator of protective immunity induced by these recombinants. Antibody responses to vaccinia virus Ag and expressed influenza virus Ag were lower in titer in beta2mu(-/-) mice than in normal B6 mice, suggesting an influence of MHC class I complexes, CD8+ T cells, or their products on antibody production. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP EPSTEIN, SL (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,MOLEC IMMUNOL LAB,BLDG 29,RM 522,BETHESDA,MD 20892, USA. NR 49 TC 70 Z9 72 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 1993 VL 150 IS 12 BP 5484 EP 5493 PG 10 WC Immunology SC Immunology GA LH978 UT WOS:A1993LH97800029 PM 8390536 ER PT J AU ARCHER, DE KESSLER, DA AF ARCHER, DE KESSLER, DA TI FOODBORNE ILLNESS IN THE 1990S SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP ARCHER, DE (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 4 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 JUN 2 PY 1993 VL 269 IS 21 BP 2737 EP 2737 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LD671 UT WOS:A1993LD67100016 PM 8492396 ER PT J AU KESSLER, DA AF KESSLER, DA TI INTRODUCING MEDWATCH - A NEW APPROACH TO REPORTING MEDICATION AND DEVICE ADVERSE-EFFECTS AND PRODUCT PROBLEMS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article RP KESSLER, DA (reprint author), US FDA,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 19 TC 199 Z9 202 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 2 PY 1993 VL 269 IS 21 BP 2765 EP 2768 DI 10.1001/jama.269.21.2765 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LD671 UT WOS:A1993LD67100027 PM 8492403 ER PT J AU RHEINSTEIN, PH KLONTZ, KC AF RHEINSTEIN, PH KLONTZ, KC TI SHELLFISH-BORNE ILLNESSES SO AMERICAN FAMILY PHYSICIAN LA English DT Article RP RHEINSTEIN, PH (reprint author), US FDA,MED STAFF,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 2 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 1993 VL 47 IS 8 BP 1837 EP 1840 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA LF546 UT WOS:A1993LF54600019 PM 8498290 ER PT J AU ZHANG, J HERMAN, EH FERRANS, VJ AF ZHANG, J HERMAN, EH FERRANS, VJ TI DENDRITIC CELLS IN THE HEARTS OF SPONTANEOUSLY HYPERTENSIVE RATS TREATED WITH DOXORUBICIN WITH OR WITHOUT ICRF-187 SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MEDIATED CYTO-TOXICITY; ADRIAMYCIN-INDUCED AUGMENTATION; (+/-)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE ICRF-187; MONOCLONAL-ANTIBODIES; ANTIGEN EXPRESSION; CARDIOTOXICITY; MACROPHAGE; CANCER; HETEROGENEITY; PRETREATMENT AB Histological and immunohistochemical studies using specific monoclonal antibodies were made to evaluate the severity of the chronic cardiomyopathy and the quantitative changes in interstitial dendritic cells (antigen-presenting cells), T helper lymphocytes, T cytotoxic/suppressor lymphocytes, and macrophages in the hearts of spontaneously hypertensive rats (SHRs) treated with doxorubicin at 1 mg/kg per week for 3, 6, 9 or 12 weeks. In addition, an assessment was made of the modifications of the responses of these cell populations by pretreatment of the SHR with ICRF-187, which protects against doxorubicin cardiotoxicity. The number of interstitial dendritic cells/mm2 of section of left ventricle was similar in saline-treated control SHRs (76 +/- 6) and in those treated with ICRG-187 alone (75 +/- 2) but increased markedly (319 +/- 33) in animals receiving a total cumulative dose of 12 mg/kg doxorubicin. Treatment with ICRF-187 prior to each administration of doxorubicin attenuated in a dose-dependent manner the increase in numbers of dendritic cells induced by doxorubicin (231 +/- 47,174 +/- 11, and 100 +/- 16 cells/mm2) after treatment with 6.25, 12.5, and 25 mg of ICRF-187, respectively. Doxorubicin also induced increases in the numbers of T helper lymphocytes and macrophages but not of T cytotoxic/suppressor lymphocytes. These increases were also attenuated by pretreatment with ICRF-187. These data were interpreted as indicating that doxorubicin cardiotoxicity results in the release of substances that initiate immune reactions involving the antigen-presenting cells of the heart and that such reactions are attenuated by pretreatment with ICRF-187. C1 NHLBI,PATHOL BRANCH,ULTRASTRUCT SECT,BLDG 10,ROOM 2N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. US FDA,DIV RES & TRAINING,LAUREL,MD. NR 34 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 1993 VL 142 IS 6 BP 1916 EP 1926 PG 11 WC Pathology SC Pathology GA LF978 UT WOS:A1993LF97800027 PM 8506959 ER PT J AU WYSOWSKI, DK FREIMAN, JP TOURTELOT, JB HORTON, ML AF WYSOWSKI, DK FREIMAN, JP TOURTELOT, JB HORTON, ML TI FATAL AND NONFATAL HEPATOTOXICITY ASSOCIATED WITH FLUTAMIDE SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE FLUTAMIDE; HEPATITIS, TOXIC; JAUNDICE; PROSTATIC NEOPLASMS; PROSTATIC HYPERTROPHY ID CARCINOMA; HEPATITIS; PROSTATE; FAILURE; CANCER AB Objective: To identify and describe patients with hepatotoxicity possibly caused by flutamide, an antiandrogen drug. Design: Case series of reports, submitted to the Adverse Drug Event Reporting System of the Food and Drug Administration. Setting. Outpatient clinics and physicians' offices in the United States. Patients: Nineteen patients treated with flutamide for prostate cancer or benign prostatic hypertrophy (for Investigation of a New Drug or off-label use). Measurements: Evidence of increased liver enzyme levels, hyperbilirubinemia, associated clinical symptoms, and diagnoses of cholestatic hepatitis. Autopsy reports were used when available. Results: From the time of marketing of flutamide in February 1989 through March 1991, the Food and Drug Administration received reports of 19 patients in the United States who developed serious hepatotoxicity while using flutamide. Fourteen patients had resolution of abnormal liver function test results after discontinuing or decreasing the dose of flutamide, but five patients died of progressive liver disease. Autopsy reports from three patients and abnormal pathologic results from three other patients (reported to the Food and Drug Administration or in the medical literature) showed hepatocellular necrosis and possibly cholestasis. Thorough work-ups excluded other possible causes than flutamide. Conclusions: Flutamide appears to cause hepatotoxic effects in certain patients. Physicians should tell patients to immediately report to physicians nausea, vomiting, fatigue, jaundice, and other signs and symptoms of liver injury. C1 OAKLAND NAVAL HOSP,OAKLAND,CA. RP WYSOWSKI, DK (reprint author), US FDA,DIV EPIDEMIOL & SURVEILLANCE,HFD-733,5600 FISHERS LANE,ROOM 15B-18,ROCKVILLE,MD 20857, USA. NR 19 TC 143 Z9 146 U1 1 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 1 PY 1993 VL 118 IS 11 BP 860 EP 864 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA LD252 UT WOS:A1993LD25200006 PM 7683180 ER PT J AU CLEARY, JD HAYMAN, J SHERWOOD, J LASALA, GP PIAZZAHEPP, T AF CLEARY, JD HAYMAN, J SHERWOOD, J LASALA, GP PIAZZAHEPP, T TI AMPHOTERICIN-B OVERDOSE IN PEDIATRIC-PATIENTS WITH ASSOCIATED CARDIAC-ARREST SO ANNALS OF PHARMACOTHERAPY LA English DT Note ID PHARMACOKINETICS; INFUSION; NEPHROTOXICITY; TOXICITY; NEONATE; INFANTS; HUMANS AB OBJECTIVE: To report the first five cases of amphotericin B overdose with secondary cardiac complications in a pediatric population. Treatment is also presented. SETTING: Hospital. PATIENTS: Two infants and three children inpatients receiving amphotericin B. INTERVENTIONS AND RESULTS: Cardiac complications were observed in five pediatric patients who received between 4.6 and 40.8 mg/kg/d of amphotericin B. Cardiac arrest occurred in all patients, and four patients died. A detailed description of the cardiac event is provided for one patient who was on a cardiac monitor during the adverse reaction. Hydrocortisone prophylaxis and verapamil therapy were the primary therapies used in patient 1 (the only survivor). Evaluation of the literature provides substantial evidence for the use of hydrocortisone in prevention of cardiac arrhythmias. CONCLUSIONS: Amphotericin B overdose can be fatal in children and infants. The presentation in humans appears similar to that in dogs where cardiac arrhythmias occurred at doses of 5-15 mg/kg. Hydrocortisone may decrease the incidence of mortality associated with cardiac arrhythmias in children receiving amphotericin B overdoses. Animal studies are necessary to evaluate this observation and potential disadvantages of hydrocortisone usage. C1 CHILDRENS CLIN,JACKSON,MS. PARKLAND MEM HOSP & AFFILIATED INST,PHARM SERV,DALLAS,TX 75235. UNIV MISSISSIPPI,MED CTR,SCH MED,JACKSON,MS 39216. US FDA,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857. RP CLEARY, JD (reprint author), UNIV MISSISSIPPI,SCH PHARM,2500 N STATE ST,JACKSON,MS 39216, USA. NR 26 TC 20 Z9 20 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUN PY 1993 VL 27 IS 6 BP 715 EP 719 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LJ025 UT WOS:A1993LJ02500007 PM 8329789 ER PT J AU RAFII, F CERNIGLIA, CE AF RAFII, F CERNIGLIA, CE TI COMPARISON OF THE AZOREDUCTASE AND NITROREDUCTASE FROM CLOSTRIDIUM-PERFRINGENS SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID INTESTINAL BACTERIA; ANAEROBIC-BACTERIA; REDUCTION; AZO; PURIFICATION; DYES AB The purified azoreductase and nitroreductase of Clostridium perfringens, which have similar electrophoretic properties, both reacted in a Western blot (immunoblot) with a polyclonal antibody raised against the azoreductase. The activity of both enzymes was enhanced by flavin adenine dinucleotide and was inhibited by menadione, o-iodosobenzoic acid, and the antibody against azoreductase. Reduction of the azo dye Direct Blue 15 by the azoreductase was inhibited by nitroaromatic compounds. The apparent K(m) of the enzyme for reduction of Direct Blue 15 in the presence of 1-nitropyrene was higher than the K(m) with the azo dye alone, demonstrating competitive inhibition. The data show that the same protein is involved in the reduction of both azo dyes and nitroaromatic compounds. C1 US FDA,NATL CTR TOXICOL RES,DIV MICROBIOL,JEFFERSON,AR 72079. NR 24 TC 40 Z9 47 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUN PY 1993 VL 59 IS 6 BP 1731 EP 1734 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA LF171 UT WOS:A1993LF17100006 PM 8328797 ER PT J AU POTHULURI, JV FREEMAN, JP EVANS, FE CERNIGLIA, CE AF POTHULURI, JV FREEMAN, JP EVANS, FE CERNIGLIA, CE TI BIOTRANSFORMATION OF FLUORENE BY THE FUNGUS CUNNINGHAMELLA-ELEGANS SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Note ID POLYCYCLIC AROMATIC-HYDROCARBONS; PHANEROCHAETE-CHRYSOSPORIUM; FLUORANTHENE; DEGRADATION AB The metabolism of fluorene, a tricyclic aromatic hydrocarbon, by Cunninghamella elegans ATCC 36112 was investigated. Approximately 69% of the [9-C-14]fluorene added to cultures was metabolized within 120 h. The major ethyl acetate-soluble metabolites were 9-fluorenone (62%), 9-fluorenol, and 2-hydroxy-9-fluorenone (together, 7.0%). Similarly to bacteria, C. elegans oxidized fluorene at the C-9 position of the five-member ring to form an alcohol and the corresponding ketone. In addition, C. elegans produced the novel metabolite 2-hydroxy-9-fluorenone. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 26 TC 25 Z9 26 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 1993 VL 59 IS 6 BP 1977 EP 1980 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA LF171 UT WOS:A1993LF17100049 PM 8328814 ER PT J AU STEHLY, GR PLAKAS, SM AF STEHLY, GR PLAKAS, SM TI PHARMACOKINETICS, TISSUE DISTRIBUTION, AND METABOLISM OF NITROFURANTOIN IN THE CHANNEL CATFISH (ICTALURUS-PUNCTATUS) SO AQUACULTURE LA English DT Article ID RENAL EXCRETION; DISPOSITION AB The pharmacokinetics, tissue distribution, and metabolism of the drug nitrofurantoin were examined in the channel catfish (Ictalurus punctatus) after intravascular or oral dosing. Mean plasma concentrations of nitrofurantoin after intravascular administration at 1 and 10 mg kg-1 of body weight were best fit to two- and three-compartment pharmacokinetic models, respectively. Nitrofurantoin was rapidly eliminated from the plasma after intravascular dosing; at 1 and 10 mg kg-1, the terminal half-lives were 23 and 46 min, respectively. After oral dosing at 1 mg kg-1, peak plasma concentrations (0.06 mug ml-1) occurred at 2 h; the bioavailability was 17%. Residues of nitrofurantoin and its metabolites in the tissues were initially eliminated rapidly but persisted at the later sampling times. Residue concentrations were highest in the plasma and excretory tissues. Approximately 21% and 4% of the oral dose were eliminated in the urine and bile, respectively. Parent nitrofurantoin was the major radiolabelled compound found in the urine; however, the percentage of total residues composed of metabolites increased with time. Biliary residues consisted mostly of nitrofurantoin metabolites. High-performance liquid chromatography revealed the presence of at least five metabolites in the urine and bile. C1 US FDA,GULF SEAFORD LAB,DAUPHIN ISL,AL. NR 17 TC 13 Z9 16 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0044-8486 J9 AQUACULTURE JI Aquaculture PD JUN 1 PY 1993 VL 113 IS 1-2 BP 1 EP 10 DI 10.1016/0044-8486(93)90335-V PG 10 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA LJ316 UT WOS:A1993LJ31600001 ER PT J AU ALAYASH, AI FRATANTONI, JC BONAVENTURA, C BONAVENTURA, J CASHON, RE AF ALAYASH, AI FRATANTONI, JC BONAVENTURA, C BONAVENTURA, J CASHON, RE TI NITRIC-OXIDE BINDING TO HUMAN FERRIHEMOGLOBINS CROSS-LINKED BETWEEN EITHER ALPHA-SUBUNIT OR BETA-SUBUNIT SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HUMAN-HEMOGLOBIN; SUPEROXIDE; SUBSTITUTE; RELEASE; INJURY C1 DUKE UNIV,CTR MARINE BIOMED,BEAUFORT,NC 28516. RP ALAYASH, AI (reprint author), US FDA,CTR BIOL EVALUAT & RES,BLDG 29,ROOM B-10,8800 ROCKVILLE PIKE,BETHESDA,MD 20014, USA. NR 46 TC 69 Z9 69 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN PY 1993 VL 303 IS 2 BP 332 EP 338 DI 10.1006/abbi.1993.1292 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LG146 UT WOS:A1993LG14600022 PM 8512319 ER PT J AU FELSON, DT ANDERSON, JJ BOERS, M BOMBARDIER, C CHERNOFF, M FRIED, B FURST, D GOLDSMITH, C KIESZAK, S LIGHTFOOT, R PAULUS, H TUGWELL, P WEINBLATT, M WIDMARK, R WILLIAMS, HJ WOLFE, F AF FELSON, DT ANDERSON, JJ BOERS, M BOMBARDIER, C CHERNOFF, M FRIED, B FURST, D GOLDSMITH, C KIESZAK, S LIGHTFOOT, R PAULUS, H TUGWELL, P WEINBLATT, M WIDMARK, R WILLIAMS, HJ WOLFE, F TI THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY PRELIMINARY CORE SET OF DISEASE-ACTIVITY MEASURES FOR RHEUMATOID-ARTHRITIS CLINICAL-TRIALS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HEALTH-STATUS MEASURE; INCREASED MORTALITY; OUTCOME ASSESSMENT; QUESTIONNAIRE; SENSITIVITY; DISABILITY; QUALITY; PATIENT; DEATH; TIME AB Objective. To develop a set of disease activity measures for use in rheumatoid arthritis (RA) clinical trials, as well as to recommend specific methods for assessing each outcome measure. This is not intended to be a restrictive list, but rather, a core set of measures that should be included in all trials. Methods. We evaluated disease activity measures commonly used in RA trials, to determine which measures best met each of 5 types of validity: construct, face, content, criterion, and discriminant. The evaluation consisted of an initial structured review of the literature on the validity of measures, with an analysis of data obtained from clinical trials to fill in gaps in this literature. A committee of experts in clinical trials, health services research, and biostatistics reviewed the validity data. A nominal group process method was used to reach consensus on a core set of disease activity measures. This set was then reviewed and finalized at an international conference on outcome measures for RA clinical trials. The committee also selected specific ways to assess each outcome. Results. The core set of disease activity measures consists of a tender joint count, swollen joint count, patient's assessment of pain, patient's and physician's global assessments of disease activity, patient's assessment of physical function, and laboratory evaluation of 1 acute-phase reactant. Together, these measures sample the broad range of improvement in RA (have content validity), and all are at least moderately sensitive to change (have discriminant validity). Many of them predict other important long-term outcomes in RA, including physical disability, radiographic damage, and death. Other disease activity measures frequently used in clinical trials were not chosen for any one of several reasons, including insensitivity to change or duplication of information provided by one of the core measures (e.g., tender joint score and tender joint count). The committee also proposes specific ways of measuring each outcome. Conclusion. We propose a core set of outcome measures for RA clinical trials. We hope this will decrease the number of outcomes assessed and standardize outcomes assessments. Further, we hope that these measures will be found useful in long-term studies. C1 UNIV LIMBURG HOSP,MAASTRICHT,NETHERLANDS. UNIV TORONTO,WELLESLEY HOSP,TORONTO M4Y 1J3,ONTARIO,CANADA. UNIV N CAROLINA,CHAPEL HILL,NC 27514. VIRGINIA MASON MED CTR,SEATTLE,WA 98101. MCMASTER UNIV,HAMILTON L8S 4L8,ONTARIO,CANADA. AMER COLL RHEUMATOL,ATLANTA,GA. UNIV KENTUCKY,LEXINGTON,KY 40506. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. UNIV OTTAWA,OTTAWA K1N 6N5,ONTARIO,CANADA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. US FDA,CDER,ROCKVILLE,MD 20857. UNIV UTAH,SALT LAKE CITY,UT 84112. ARTHRITIS CTR,WICHITA,KS. RP FELSON, DT (reprint author), BOSTON UNIV,CTR ARTHRITIS,BOSTON,MA 02215, USA. OI Tugwell, Peter/0000-0001-5062-0556 NR 56 TC 1132 Z9 1155 U1 4 U2 25 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1993 VL 36 IS 6 BP 729 EP 740 DI 10.1002/art.1780360601 PG 12 WC Rheumatology SC Rheumatology GA LH465 UT WOS:A1993LH46500001 PM 8507213 ER PT J AU SEAMON, KB AF SEAMON, KB TI EVALUATION OF GENETIC STABILITY SO BIOLOGICALS LA English DT Article; Proceedings Paper CT WORKSHOP ON GENETIC STABILITY AND PRODUCT CONSISTENCY OF RDNA DERIVED BIOLOGICALS CY NOV 23, 1992 CL NATL INST BIOL STAND & CONTROL, LONDON, ENGLAND SP WHO, NATL INST BIOL STAND & CONTROL HO NATL INST BIOL STAND & CONTROL RP SEAMON, KB (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUN PY 1993 VL 21 IS 2 BP 153 EP 154 DI 10.1006/biol.1993.1066 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA MH533 UT WOS:A1993MH53300015 PM 8297597 ER PT J AU SAWYER, LA MCINNIS, J ALBRECHT, P AF SAWYER, LA MCINNIS, J ALBRECHT, P TI QUANTITATION OF D-ANTIGEN CONTENT IN INACTIVATED POLIOVIRUS VACCINE DERIVED FROM WILD-TYPE OR SABIN STRAINS SO BIOLOGICALS LA English DT Article ID MONOCLONAL-ANTIBODIES; NEUTRALIZATION EPITOPES; TESTS RP SAWYER, LA (reprint author), CTR BIOL EVALUAT & RES,DIV VIRAL PROD,PEDIAT DIS LAB,1401 ROCKVILLE PIKE,HFM-460,ROCKVILLE,MD 20852, USA. NR 20 TC 16 Z9 19 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUN PY 1993 VL 21 IS 2 BP 169 EP 177 DI 10.1006/biol.1993.1070 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA MH533 UT WOS:A1993MH53300019 PM 8297601 ER PT J AU GILKS, WR WANG, CC YVONNET, B COURSAGET, P AF GILKS, WR WANG, CC YVONNET, B COURSAGET, P TI RANDOM-EFFECTS MODELS FOR LONGITUDINAL DATA USING GIBBS SAMPLING SO BIOMETRICS LA English DT Article DE BAYESIAN INFERENCE; CENSORED DATA; CONVERGENCE; GIBBS SAMPLING; HEPATITIS-B IMMUNIZATION; HETEROGENEITY; LONGITUDINAL DATA; RANDOM EFFECTS; VARIANCE COMPONENTS ID HEPATITIS-B VACCINE; MAXIMUM-LIKELIHOOD; LINEAR-MODELS; BAYES FACTORS; ALGORITHM AB Analysis of longitudinal studies is often complicated through differences amongst individuals in the number and spacing of observations. Laird and Ware (1982, Biometrics 38, 963-974) proposed a linear random-effects model to deal with this problem. We propose a generalisation of this model to accommodate multiple random effects, and show how Gibbs sampling can be used to estimate it. We illustrate the methodology with an analysis of long-term response to hepatitis B vaccination, and demonstrate that the methodology can be easily and effectively extended to deal with censoring in the dependent variable. C1 FDA,CBER,DIV BIOSTAT & EPIDEMIOL,BETHESDA,MD. FAC PHARM TOURS,INST VIROL,TOURS,FRANCE. FAC PHARM TOURS,MICROBIOL LAB,TOURS,FRANCE. RP GILKS, WR (reprint author), INST PUBL HLTH,MED RES COUNCIL,BIOSTAT UNIT,ROBINSON WAY,CAMBRIDGE CB2 2BW,ENGLAND. NR 35 TC 60 Z9 60 U1 0 U2 7 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 1993 VL 49 IS 2 BP 441 EP 453 DI 10.2307/2532557 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LN254 UT WOS:A1993LN25400011 PM 8369380 ER PT J AU OGRETMEN, B RATAJCZAK, H KATS, A STARK, BC GENDEL, SM AF OGRETMEN, B RATAJCZAK, H KATS, A STARK, BC GENDEL, SM TI EFFECTS OF STAINING OF RNA WITH ETHIDIUM-BROMIDE BEFORE ELECTROPHORESIS ON PERFORMANCE OF NORTHERN BLOTS SO BIOTECHNIQUES LA English DT Note AB Staining of RNA with ethidium bromide (EtdBr) prior to running agarose gels has been reported to afford certain advantages over staining gels after electrophoresis We have examined prior staining of RNA with a wide range of EtdBr concentrations, particularly with respect to its effects on Northern blot hybridizations using antisense RNA probes. Prior staining with EtdBr at concentrations of 100-1000 mug/ml caused significant alterations in RNA mobilities and significantly decreased hybridization with antisense RIVA probes compared with unstained RNA. Prior staining with EtdBr at 10-50 mug/ml resulted in the best combination of staining sensitivity, absence of alterations in RNA mobility and efficiency of hybridization. Conventional staining of gels after electrophoresis also resulted in decreased hybridization efficiency with RNA probes compared with unstained RNA. C1 IIT,DEPT BIOL,CHICAGO,IL 60616. IIT CTR,RES INST,DEPT LIFE SCI,CHICAGO,IL 60616. US FDA,NATL CTR FOOD SAFETY & TECHNOL,SUMMIT ARGO,IL 60501. FU FDA HHS [FD-000431] NR 7 TC 23 Z9 23 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 1993 VL 14 IS 6 BP 932 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LF326 UT WOS:A1993LF32600016 PM 7687448 ER PT J AU TAGA, K MOSTOWSKI, H TOSATO, G AF TAGA, K MOSTOWSKI, H TOSATO, G TI HUMAN INTERLEUKIN-10 CAN DIRECTLY INHIBIT T-CELL GROWTH SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; CYTOKINE PRODUCTION; MONOCLONAL-ANTIBODIES; IL-10; PROLIFERATION; LYMPHOCYTES; ACTIVATION; MATURE; SIGNAL RP TAGA, K (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BLDG 29A,ROOM 2D06,BETHESDA,MD 20892, USA. NR 30 TC 237 Z9 243 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1993 VL 81 IS 11 BP 2964 EP 2971 PG 8 WC Hematology SC Hematology GA LF065 UT WOS:A1993LF06500017 PM 8499633 ER PT J AU ELESPURU, RK SAAVEDRA, JE KOVATCH, RM LIJINSKY, W AF ELESPURU, RK SAAVEDRA, JE KOVATCH, RM LIJINSKY, W TI EXAMINATION OF ALPHA-CARBONYL DERIVATIVES OF NITROSODIMETHYLAMINE AND ETHYLNITROSOMETHYLAMINE AS PUTATIVE PROXIMATE CARCINOGENS SO CARCINOGENESIS LA English DT Article ID N-NITROSO-COMPOUNDS; MUTAGENS; LIVER; RATS AB Metabolites produced by enzymic oxidation are believed to be responsible for the mutagenicity and carcinogenicity of N-nitrosamines. Although alpha-hydroxy compounds are often considered, a related and more stable oxidation product, the alpha-carbonyl compound, was studied here. The alpha-carbonyl derivatives of nitrosodimethylamine (NDMA) and ethylnitrosomethylamine (oxidized at either the methyl or the ethyl group) were synthesized. The derivatives were methylnitrosoformamide (MNFA), ethylnitrosoformamide (ENFA) and methylnitrosoacetamide (MNAA). These compounds were then studied as potential toxic, mutagenic and carcinogenic intermediates. All three compounds were very potent directly acting mutagens to Salmonella typhimurium TA1535. Mutational Fingerprints in Escherichia coli of MNFA and ENFA (but not MNAA) matched those produced by S(N)1-type methylating and ethylating compounds respectively. The latter results indicate that the two alkylnitrosoformamides could be intermediates in the mutagenicity of the parent nitrosamines. In animal studies the putative metabolite MNFA was more acutely toxic than NDMA in F344 rats. In chronic experiments with MNFA in F344 rats and Syrian golden hamsters, tumors of the forestomach were induced by oral administration in most animals (except female hamsters) within 8 months. The properties of these oxidized derivatives of N-nitrosamines are consistent with expectations for proximate carcinogenic intermediates. C1 US FDA,MOLEC BIOL BRANCH,HFZ-113,5600 FISHERS LANE,ROCKVILLE,MD 20857. FREDERICK CANC RES & DEV CTR,ABI,BASIC RES PROGRAM,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO-74101] NR 22 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1993 VL 14 IS 6 BP 1189 EP 1193 DI 10.1093/carcin/14.6.1189 PG 5 WC Oncology SC Oncology GA LG261 UT WOS:A1993LG26100019 PM 8508506 ER PT J AU FULLERTON, FR GREENMAN, DL BLAYDES, BS POIRIER, LA AF FULLERTON, FR GREENMAN, DL BLAYDES, BS POIRIER, LA TI ETHYNYLESTRADIOL PROTECTION AGAINST METHYL INSUFFICIENCY IN CASTRATED MALE WISTAR FURTH RATS FED A METHIONINE-CHOLINE-DEFICIENT DIET SO CARCINOGENESIS LA English DT Note ID ADENOSYL-L-METHIONINE; ORAL-CONTRACEPTIVE STEROIDS; SPRAGUE-DAWLEY RATS; ACID-DEFINED DIETS; ETHINYL ESTRADIOL; BILE SECRETION; DEVOID DIET; FEMALE RATS; WF RATS; LIVER AB The interactive effects of dietary methyl insufficiency and the estrogenic compound ethynylestradiol (EE) on the levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) were examined in the liver, lungs and pancreas of rats. In addition, such effects on the hepatic content of 5-methyldeoxycytidine (5-MC) in nuclear DNA were determined. Castrated male Wistar/Furth rats were fed various levels of EE in either: (i) a complete, amino acid-defined diet (diet 1); (ii) the same diet lacking in choline and methionine and supplemented with 0.9% of DL-homocystine (equimolar to methionine) (diet 2); or (iii) diet 2 but only with 0.3% DL-homocystine (diet 2M). Methyl deficiency and EE each independently produced decreased weight gains and increased relative liver weights (liver weight relative to total body weight) compared with control animals. Livers from rats fed diets 2 and 2M without EE had lower levels of SAM and lower SAM:SAH ratios than did the livers from diet 1-fed rats not treated with EE. Hepatic SAM:SAH ratios in diet 1-fed rats were not altered by EE treatment. However, EE treatment increased the hepatic contents of SAM and restored the SAM:SAH levels to normal in rats fed diet 2 or 2M. The levels of SAM + SAH in the livers of rats fed the low homocystine diet (diet 2M) were less than in those fed either diet 1 or diet 2. Thus, the addition of EE at 10 p.p.m. gave protection against reduced levels of SAM, and reduced SAM:SAH ratios in the liver, but had little effect when added to the methyl-adequate diet. No differences in hepatic 5-MC levels were observed in any of the groups as a result of either methyl deficiency or EE treatment. Methyl deprivation alone caused no discernible difference in pancreatic SAM levels but did result in a significant rise in SAH levels and thus in decreased SAM:SAH ratios. EE had no consistent effect on pancreatic SAM, SAH or SAM:SAH ratios in any of the diet groups examined. Similarly, the chronic feeding of diet 2, diet 2M or of EE had no significant effect on the SA.M contents of lungs, compared with the corresponding levels in control rats. The protection conferred by EE against SAM insufficiency in the livers of rats fed a methionine- and choline-deficient diet is consistent with the relative insensitivity of female rats to the hepatotoxicity of dietary methyl insufficiency. RP FULLERTON, FR (reprint author), NATL CTR TOXICOL RES,DIV NUTR TOXICOL,JEFFERSON,AR 72079, USA. NR 32 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1993 VL 14 IS 6 BP 1237 EP 1240 DI 10.1093/carcin/14.6.1237 PG 4 WC Oncology SC Oncology GA LG261 UT WOS:A1993LG26100028 PM 8508512 ER PT J AU HONIG, PK WORTHAM, DC ZAMANI, K MULLIN, JC CONNER, DP CANTILENA, LR AF HONIG, PK WORTHAM, DC ZAMANI, K MULLIN, JC CONNER, DP CANTILENA, LR TI THE EFFECT OF FLUCONAZOLE ON THE STEADY-STATE PHARMACOKINETICS AND ELECTROCARDIOGRAPHIC PHARMACODYNAMICS OF TERFENADINE IN HUMANS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CYCLOSPORINE AB Terfenadine is rapidly and nearly completely biotransformed during a first pass to an active acid metabolite. Accumulation of unmetabolized terfenadine has been associated with altered cardiac repolarization. Drug-drug interactions resulting in the accumulation of terfenadine have been reported for ketoconazole and erythromycin. Six subjects were given the recommended dose of terfenadine (60 mg every 12 hours) for 7 days before initiation of oral fluconazole (200 mg once daily). The mean metabolite area under the concentration-time curve increased by 34% and the time to maximum concentration of the metabolite was delayed from 2.3 to 4 hours by concurrent fluconazole. Unmetabolized terfenadine was not present in any subject, and cardiac repolarization was not significantly changed from baseline during any phase of the study. We conclude that a pharmacokinetic interaction between terfenadine and fluconazole exists; however, the absence of accumulation of parent terfenadine in plasma suggests that a clinically significant interaction is unlikely. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,DIV CLIN PHARMACOL,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,DIV CARDIOL,WASHINGTON,DC 20307. US FDA,ROCKVILLE,MD 20857. RI Zamani, Kaveh/A-9182-2011 FU FDA HHS [FDA 224-88-3006] NR 26 TC 78 Z9 78 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 1993 VL 53 IS 6 BP 630 EP 636 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LJ938 UT WOS:A1993LJ93800003 PM 8513654 ER PT J AU SAAVEDRADELGADO, AM METCALFE, DD AF SAAVEDRADELGADO, AM METCALFE, DD TI SEAFOOD TOXINS SO CLINICAL REVIEWS IN ALLERGY LA English DT Review ID FISH; CIGUATERA; DINOFLAGELLATE; SHELLFISH; OUTBREAKS C1 NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BLDG 10,RM 11C210,BETHESDA,MD 20892. CTR DRUG EVALUAT & RES,DIV ONCOL & PULM DRUG PROD,ROCKVILLE,MD. NR 51 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0731-8235 J9 CLIN REV ALLERG JI Clin. Rev. Allergy PD SUM PY 1993 VL 11 IS 2 BP 241 EP 260 PG 20 WC Allergy SC Allergy GA LU469 UT WOS:A1993LU46900006 PM 8221511 ER PT J AU ROSENKRANZ, HS MATTHEWS, EJ KLOPMAN, G AF ROSENKRANZ, HS MATTHEWS, EJ KLOPMAN, G TI COMMONALITIES IN THE STRUCTURAL DETERMINANTS OF TOXICITY IN FISH AND MAMMALS SO ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY LA English DT Article ID SISTER CHROMATID EXCHANGES; HAMSTER OVARY CELLS; CHROMOSOMAL-ABERRATIONS; MUTAGENICITY; INDUCTION C1 US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. CASE WESTERN RESERVE UNIV,DEPT CHEM,CLEVELAND,OH 44106. RP ROSENKRANZ, HS (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15261, USA. FU NIEHS NIH HHS [ES04659] NR 8 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0147-6513 J9 ECOTOX ENVIRON SAFE JI Ecotox. Environ. Safe. PD JUN PY 1993 VL 25 IS 3 BP 296 EP 299 DI 10.1006/eesa.1993.1027 PG 4 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA LH212 UT WOS:A1993LH21200004 PM 7691523 ER PT J AU FREAS, DL CORRELL, PH DOUGHERTY, SF KARLSSON, S PLUZNIK, DH AF FREAS, DL CORRELL, PH DOUGHERTY, SF KARLSSON, S PLUZNIK, DH TI EVALUATION OF EXPRESSION OF TRANSFERRED GENES IN DIFFERENTIATING MYELOID CELLS - EXPRESSION OF HUMAN GLUCOCEREBROSIDASE IN MURINE MACROPHAGES SO HUMAN GENE THERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; MOLECULAR-CLONING; LEUKEMIA CELLS; RETROVIRUS; CDNA; M1; INVIVO; MICE; SAFE AB The retroviral vector LGSN, in which the human glucocerebrosidase (GC) cDNA is driven by the Moloney murine leukemia virus (MoMLV) long terminal repeat (LTR), was tested for expression in the murine myelomonocytic leukemia cell line M1 before and after induction of differentiation with interleukin-6 (IL-6). Southern analysis of the seven transduced clones selected for neomycin resistance in Geneticin (G-418 sulfate) demonstrated one to eight copies of intact provirus with rearrangements in only two clones. Absolute levels of human GC RNA and protein increased with increased copy numbers of provirus in the clones. Upon induction with IL-6 of the seven transduced clones to the macrophage phenotype, there was no significant change, overall, in RNA levels but some increase in human GC protein levels could be detected. Although this was the average trend, considerable clonal variation in RNA and protein levels was observed upon induction. Transduction of the M1 cells did not interfere with the ability of the cells to differentiate from blasts to macrophages as seen by the appearance of membrane receptors for the constant region of immunoglobulins (FcgammaRI) and, lysozyme production in the differentiated M1 cells. Thus, the M1 cell line can be used for testing retroviral vector expression in myeloid lineages at early and late stages of differentiation. This rapid in vitro testing of potential retroviral vectors will be beneficial for gene therapy of disorders that affect differentiated macrophages such as Gaucher's disease. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. RP FREAS, DL (reprint author), NINCDS,DMNB,MMGS,BLDG 10,ROOM 3D04,BETHESDA,MD 20892, USA. NR 31 TC 7 Z9 7 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 JUN PY 1993 VL 4 IS 3 BP 283 EP 290 DI 10.1089/hum.1993.4.3-283 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA LH389 UT WOS:A1993LH38900006 PM 7687878 ER PT J AU UMLAUF, SW BEVERLY, B KANG, SM BRORSON, K TRAN, AC SCHWARTZ, RH AF UMLAUF, SW BEVERLY, B KANG, SM BRORSON, K TRAN, AC SCHWARTZ, RH TI MOLECULAR REGULATION OF THE IL-2 GENE - RHEOSTATIC CONTROL OF THE IMMUNE-SYSTEM SO IMMUNOLOGICAL REVIEWS LA English DT Review ID T-CELL CLONES; ANTIGEN-PRESENTING CELLS; LYMPHOKINE MESSENGER-RNA; HUMAN LYMPHOCYTES-T; INTERLEUKIN-2 GENE; COSTIMULATORY SIGNAL; MONOCLONAL-ANTIBODIES; RECEPTOR OCCUPANCY; ACTIVATION PATHWAY; C-JUN C1 NIH,CELLULAR & MOLEC IMMUNOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. ANERGEN INC,REDWOOD CITY,CA 94063. CELL GENESYS INC,FOSTER CITY,CA 94404. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT SURG,SAN FRANCISCO,CA 94143. US FDA,BETHESDA,MD 20892. NR 68 TC 62 Z9 63 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1993 VL 133 BP 177 EP 197 DI 10.1111/j.1600-065X.1993.tb01516.x PG 21 WC Immunology SC Immunology GA LR370 UT WOS:A1993LR37000010 PM 8225366 ER PT J AU NORMANNO, N QI, CF GULLICK, WJ PERSICO, G YARDEN, Y WEN, DZ PLOWMAN, G KENNEY, N JOHNSON, G KIM, N BRANDT, R MARTINEZLACACI, I DICKSON, RB SALOMON, DS AF NORMANNO, N QI, CF GULLICK, WJ PERSICO, G YARDEN, Y WEN, DZ PLOWMAN, G KENNEY, N JOHNSON, G KIM, N BRANDT, R MARTINEZLACACI, I DICKSON, RB SALOMON, DS TI EXPRESSION OF AMPHIREGULIN, CRIPTO-1, AND HEREGULIN-ALPHA IN HUMAN BREAST-CANCER CELLS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE BREAST CANCER; CRIPTO; EPIDERMAL GROWTH FACTOR; AMPHIREGULIN; HEREGULIN-ALPHA ID GROWTH-FACTOR-ALPHA; MESSENGER RIBONUCLEIC-ACID; EPITHELIAL-CELLS; TRANSGENIC MICE; MAMMARY-GLAND; LINE MCF-7; TGF-ALPHA; GENE; OVEREXPRESSION; TRANSFORMATION AB Cripto-1 (CR-1), amphiregulin (AR), and heregulin alpha (HRGalpha) are three recently discovered epidermal growth factor (EGF)-related peptides. The expression of these proteins was determined in MCF-7, ZR-75-1, T-47D, SK-BR-3, MDA-MB-231, MDA-MB-468, and Hs-578T human breast cancer cell lines using reverse transcriptase-polymerase chain reaction (RT-PCR), Northern blotting, and immunocytochemistry (ICC). The expression of CR-1 mRNA was detected by RT-PCR in all of the breast cancer cell lines. AR mRNA was detected by Northern blot analysis in MCF-7, ZR-75-1, T-47D, MDA-MB-231, and MDA-MB-468 cells while HRGalpha mRNA was expressed in only MDA-MB-231 and Hs-578T cells. All estrogen receptor-positive cell lines were found to express AR mRNA, and estrogen was able to induce AR mRNA expression in estrogen-depleted MCF-7 cells. CR-1 and AR proteins could be immunocytochemically detected in the breast cancer cell lines that were expressing CR-1 and AR mRNA using monospecific rabbit polyclonal antibodies. The anti-CR-1 antibody was also used to examine 26 human primary breast carcinomas by ICC for CR-1 expression. Seventy-five percent of the carcinomas were found to express the CR-1 protein while the adjacent non-involved breast epithelium was negative. These data demonstrate that CR-1, AR, and HRGalpha are coexpressed in human breast cancer cells and suggest that these three EGF-related peptides might perform a role in the autocrine growth regulation of human breast carcinoma cells. C1 NCI,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,BLDG 10,BETHESDA,MD 20892. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL LAB,LONDON W12 0HS,ENGLAND. INT INST GENET & BIOPHYS,I-80125 NAPLES,ITALY. WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. AMGEN INC,THOUSAND OAKS,CA 91320. BRISTOL MYERS SQUIBB CO,INST PHARMACEUT,SEATTLE,WA 98121. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. GEORGETOWN UNIV,LOMBARDI CANC RES CTR,WASHINGTON,DC. RI PLOWMAN, Greg/E-2012-2011; YARDEN, YOSEF/K-1467-2012; OI Normanno, Nicola/0000-0002-7158-2605 NR 54 TC 66 Z9 66 U1 1 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JUN PY 1993 VL 2 IS 6 BP 903 EP 911 PG 9 WC Oncology SC Oncology GA LC863 UT WOS:A1993LC86300007 PM 21573645 ER PT J AU HEWLETT, I JOSHI, B NORCROSS, M HOFFMANN, T RIORDAN, G EPSTEIN, J AF HEWLETT, I JOSHI, B NORCROSS, M HOFFMANN, T RIORDAN, G EPSTEIN, J TI MECHANISM OF HIV-1 INDUCTION FROM CHRONICALLY INFECTED PROMONOCYTIC CELLS BY CIGARETTE-SMOKE CONSTITUENTS, BENZO(A)PYRENE AND NNK SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 US FDA,CBER,DIV TRANSFUS SCI,BETHESDA,MD 20892. US FDA,CBER,DIV CYTOKINE BIOL,BETHESDA,MD 20892. US FDA,CBER,DIV HEMATOL,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 JUN PY 1993 VL 6 IS 6 BP 695 EP 695 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100128 ER PT J AU BLUMENTHAL, R GOLDING, H BRODER, CC BERGER, EA PURI, A DIMITROV, DS AF BLUMENTHAL, R GOLDING, H BRODER, CC BERGER, EA PURI, A DIMITROV, DS TI KINETICS OF HIV-1 ENV-MEDIATED CELL-FUSION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. CBER,BETHESDA,MD 20892. FDA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD JUN PY 1993 VL 6 IS 6 BP 704 EP 704 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100166 ER PT J AU POFFENBERGER, KL RIORDAN, G LEE, S EPSTEIN, J HEWLETT, I AF POFFENBERGER, KL RIORDAN, G LEE, S EPSTEIN, J HEWLETT, I TI LOW-LEVEL, PERSISTENT HIV-1 INFECTION OF MAMMARY EPITHELIAL-CELLS INVITRO SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS SCI,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 JUN PY 1993 VL 6 IS 6 BP 715 EP 715 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100209 ER PT J AU BETTS, M BLAY, R HOFFMAN, T GOLDING, B AF BETTS, M BLAY, R HOFFMAN, T GOLDING, B TI BRUCELLA-ABORTUS AND LIPOPOLYSACCHARIDE FROM BRUCELLA-ABORTUS INDUCE TH1-LIKE RESPONSES IN UNINFECTED AND HIV-1-INFECTED PERSONS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 US FDA,CBER,CELL BIOL LAB,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 JUN PY 1993 VL 6 IS 6 BP 716 EP 716 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100211 ER PT J AU GOLDING, H DIMITROV, D BLUMENTHAL, R GOLDING, B AF GOLDING, H DIMITROV, D BLUMENTHAL, R GOLDING, B TI FUSION OF HUMAN B-CELLS WITH HIV-1 ENVELOPE EXPRESSING T-CELLS IS ENHANCED BY ANTIGEN-SPECIFIC IMMUNOGLOBULIN (IG) RECEPTORS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 FDA,CBER,DIV VIROL,BETHESDA,MD. FDA,CBER,DIV HEMATOL,BETHESDA,MD. NCI,LMMB,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 JUN PY 1993 VL 6 IS 6 BP 722 EP 722 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LC751 UT WOS:A1993LC75100235 ER PT J AU ARAKERE, G KESSEL, M NGUYEN, N FRASCH, CE AF ARAKERE, G KESSEL, M NGUYEN, N FRASCH, CE TI CHARACTERIZATION OF A STRESS PROTEIN FROM GROUP-B NEISSERIA-MENINGITIDIS SO JOURNAL OF BACTERIOLOGY LA English DT Note ID OUTER-MEMBRANE PROTEINS; HEAT-SHOCK; GONORRHOEAE; PURIFICATION; EXPRESSION AB Increased levels of a 65-kDa stress protein (Msp65) were observed in group B Neisseria meningitidis grown under stationary-growth conditions. Electron microscopy showed two apposing rings of seven subunits, a structure typical of Escherichia coli GroEL. Msp65 was not found in either the periplasmic space or the outer membrane. Several important differences between the GroEL analogs of N. meningitidis and Neisseria gonorrhoeae are discussed. C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. UNIV MARYLAND,DEPT MICROBIOL,COLL PK,MD 20742. RP ARAKERE, G (reprint author), US FDA,DIV BACTERIAL PROD,BETHESDA,MD 20892, USA. NR 34 TC 7 Z9 11 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 JUN PY 1993 VL 175 IS 11 BP 3664 EP 3668 PG 5 WC Microbiology SC Microbiology GA LE431 UT WOS:A1993LE43100051 PM 8099073 ER PT J AU TARGOFF, IN TRIEU, EP MILLER, FW AF TARGOFF, IN TRIEU, EP MILLER, FW TI REACTION OF ANTI-OJ AUTOANTIBODIES WITH COMPONENTS OF THE MULTIENZYME COMPLEX OF AMINOACYL-TRANSFER RNA-SYNTHETASES IN ADDITION TO ISOLEUCYL-TRANSFER RNA-SYNTHETASE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE MYOSITIS; AMINO ACYL TRANSFER RNA SYNTHETASES; AUTOIMMUNITY; AUTOANTIBODIES; INTERSTITIAL LUNG DISEASE ID INTERSTITIAL LUNG-DISEASE; ANTI-JO-1 ANTIBODY; MYOSITIS; POLYMYOSITIS; DERMATOMYOSITIS; JO-1; AUTOIMMUNITY; PATIENT; MARKER; REGION AB Autoantibodies to five aminoacyl-tRNA synthetases have been reported, and all have been associated with a syndrome of myositis and interstitial lung disease. Four of these synthetases exist free in the cytoplasm, but the fifth, isoleucyl-tRNA synthetase (recognized by anti-OJ autoantibodies), is a component of the multi-enzyme complex containing at least seven synthetases. In an effort to better understand the origins of these antibodies, we examined sera from 11 patients with anti-OJ autoantibodies for evidence of reaction with other components of the complex. All sera showed a characteristic pattern of 10 protein bands by immunoprecipitation from HeLa cell extract. 10 of 11 sera significantly inhibited isoleucyl-tRNA synthetase enzyme activity. Serum and IgG from four patients also inhibited leucyl-tRNA synthetase activity, and serum and IgG from two inhibited lysyl-tRNA synthetase. Immunoblotting experiments supported reaction of the two sera with lysyl-tRNA synthetase, and revealed additional reactivity of three sera with a 160-kD component believed to be glutaminyl-tRNA synthetase. Despite reaction of some sera with additional synthetases, the immunoprecipitated tRNA appeared the same with all sera, and functioned as tRNA(ile). While reaction with more than one synthetase was seen with some anti-OJ sera, all synthetases targeted by anti-OJ sera were components of the complex, rather than unassociated synthetases. These findings suggest that an initial autoantibody response against isoleucyl-tRNA synthetase was followed by extension to involve other components of the synthetase complex. These observations may have implications for understanding the generation of antisynthetase autoantibodies. C1 UNIV OKLAHOMA HLTH SCI CTR,DEPT MED,OKLAHOMA CITY,OK 73190. VET AFFAIRS MED CTR,OKLAHOMA CITY,OK 73104. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP TARGOFF, IN (reprint author), OKLAHOMA MED RES FDN,ARTHRITIS IMMUNOL PROGRAM,825 NE 13TH ST,OKLAHOMA CITY,OK 73104, USA. OI Miller, Frederick/0000-0003-2831-9593 FU NIAID NIH HHS [AI-21568, AI-27181]; NIAMS NIH HHS [AR-32214] NR 30 TC 88 Z9 88 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1993 VL 91 IS 6 BP 2556 EP 2564 DI 10.1172/JCI116493 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LH121 UT WOS:A1993LH12100030 PM 8514867 ER PT J AU TOSATO, G JONES, K BREINIG, MK MCWILLIAMS, HP MCKNIGHT, JLC AF TOSATO, G JONES, K BREINIG, MK MCWILLIAMS, HP MCKNIGHT, JLC TI INTERLEUKIN-6 PRODUCTION IN POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE EBV; IMMUNODEFICIENCY; LYMPHOMAGENESIS; GROWTH FACTOR; TUMORIGENICITY ID EPSTEIN-BARR-VIRUS; STIMULATORY FACTOR-II; GROWTH-FACTOR; TRANSPLANT RECIPIENTS; RHEUMATOID-ARTHRITIS; B-CELLS; INFECTION; DISORDERS; SERUM; IL-6 AB IL-6, a multifunctional cytokine produced by monocytes, fibroblasts, and endothelial cells, promotes the growth of EBV-immortalized B cells in vitro and renders these cells tumorigenic in athymic mice. In the present study, serum/plasma IL-6 bioactivity was found to be abnormally elevated, albeit transiently, in 17 of 18 solid organ transplant recipients with posttransplant lymphoproliferative disease (PTLD), with a mean maximal level of 196.7 U/ml. This represents a 16.4 increase above the normal mean (11.3 U/ml). In contrast, only 3 of 10 solid organ transplant recipients with uncomplicated courses posttransplant had abnormally elevated serum/plasma IL-6 bioactivity (mean maximal level 41.4 U/ml, P = 0.0007). When transferred to single cell culture, the 11 PTLD tissues produced 640 to 1.25 x 10(6) IL-6 U/ml in the culture supernatant, with a mean maximal level of 35,025 IL-6 U/ml. Cell separation experiments demonstrated that the adherent cells, identified as non-B cells, were the principal source of IL-6 production in vitro by PTLD tissue. Control cultures of inflammatory lymphoid tissue negative for lymphoproliferative disease as well as of PBL from patients with acute EBV-induced infectious mononucleosis consistently produced < 10 IL-6 U/ml. Thus, IL-6 is produced at high levels by PTLD tissues and may play a critical role in the pathogenesis of PTLD. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT INFECT DIS & MICROBIOL,PITTSBURGH,PA 15261. RP TOSATO, G (reprint author), CTR BIOL EVALUAT & RES,IMMUNOL LAB,BLDG 29A,ROOM 2DO6,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [BRSG 2 SO7 RR05451-26, BRSD 2 SO7 RR05451-28, BRSG 2 SO7 RR05451-27] NR 38 TC 73 Z9 73 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1993 VL 91 IS 6 BP 2806 EP 2814 DI 10.1172/JCI116523 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LH121 UT WOS:A1993LH12100060 PM 8514888 ER PT J AU PLUDA, JM VENZON, DJ TOSATO, G LIETZAU, J WYVILL, K NELSON, DL JAFFE, ES KARP, JE BRODER, S YARCHOAN, R AF PLUDA, JM VENZON, DJ TOSATO, G LIETZAU, J WYVILL, K NELSON, DL JAFFE, ES KARP, JE BRODER, S YARCHOAN, R TI PARAMETERS AFFECTING THE DEVELOPMENT OF NON-HODGKINS-LYMPHOMA IN PATIENTS WITH SEVERE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION RECEIVING ANTIRETROVIRAL THERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AIDS-RELATED COMPLEX; IMMUNE-DEFICIENCY SYNDROME; HOMOSEXUAL MEN; HIV-INFECTION; MALIGNANT-LYMPHOMA; CANCER REGISTRY; B-CELLS; ZIDOVUDINE; INTERLEUKIN-6; 3'-AZIDO-3'-DEOXYTHYMIDINE C1 NCI,PATHOL LAB,MED BRANCH,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20205. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,OFF DIRECTOR,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 57 TC 139 Z9 139 U1 0 U2 1 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 JUN PY 1993 VL 11 IS 6 BP 1099 EP 1107 PG 9 WC Oncology SC Oncology GA LF310 UT WOS:A1993LF31000014 PM 8099121 ER PT J AU YAMADA, H JUNE, CH FINKELMAN, F BRUNSWICK, M RING, MS LEES, A MOND, JJ AF YAMADA, H JUNE, CH FINKELMAN, F BRUNSWICK, M RING, MS LEES, A MOND, JJ TI PERSISTENT CALCIUM ELEVATION CORRELATES WITH THE INDUCTION OF SURFACE IMMUNOGLOBULIN-MEDIATED B-CELL DNA-SYNTHESIS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PROTEIN-KINASE-C; INTRACELLULAR IONIZED CALCIUM; TYROSINE PHOSPHORYLATION; CROSS-LINKING; ANTI-IG; LYMPHOCYTES-B; MONOCLONAL-ANTIBODIES; PHOSPHOLIPASE-C; ACTIVATION; ABSENCE AB Surface immunoglobulin (sIg)-mediated stimulation of B lymphocytes induces a tyrosine kinase-dependent sequence of events leading to rapid and large elevations in intracellular ionized calcium ([Ca2+]i). These early biochemical events do not necessarily lead to proliferation of B cells, however, and conversely, the absence of or inhibition of these events does not necessarily prevent cellular proliferation. We now show by digital image analysis of single B cells that conditions which lead to B cell proliferation are associated with low-level but persistent sustained or cyclic elevations in [Ca2+]i. In marked contrast, early and nonsustained elevations in [Ca2+]i are induced in B cells by stimuli that lead to G1 transition but fail to progress to DNA synthesis. Thus, when B cells were stimulated with mitogenic and nonmitogenic anti-IgD antibodies, both of which induce entry of cells into G1 and early calcium transients of comparable magnitude, persistent low-level calcium elevations were only detected in cells stimulated with the mitogenic antibody. Furthermore, persistent calcium elevations were also seen when B cells were stimulated with a multivalent dextran-anti-Ig conjugate which induced very high levels of B cell proliferation in the absence of detectable phosphatidylinositol 4,5-biphosphate hydrolysis or elevations in [Ca2+]i as detected by flow cytometry. Finally, B cells from X-linked B cell-defective mice, which do not proliferate in response to anti-Ig antibody, show marked and early increases in [Ca2+]i, but do not show persistent calcium elevations. These data suggest that the rapid and large increases of [Ca2+]i seen in lymphocytes within seconds after antigen receptor ligation may be associated with entry in G1, whereas low-level but persistent elevations may be the hallmark of a cell destined to synthesize DNA. C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,MAIL STOP 44,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. US FDA,CELL BIOL LAB,BETHESDA,MD 20892. GEOCENTERS INC,FT WASHINGTON,MD 20744. FU NIAID NIH HHS [AI-21328, AI-27465] NR 33 TC 42 Z9 42 U1 0 U2 2 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 1 PY 1993 VL 177 IS 6 BP 1613 EP 1621 DI 10.1084/jem.177.6.1613 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LD660 UT WOS:A1993LD66000011 PM 8496680 ER PT J AU OFFIT, PA HOFFENBERG, EJ SANTOS, N GOUVEA, V AF OFFIT, PA HOFFENBERG, EJ SANTOS, N GOUVEA, V TI ROTAVIRUS-SPECIFIC HUMORAL AND CELLULAR IMMUNE-RESPONSE AFTER PRIMARY, SYMPTOMATIC INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SEROLOGIC RESPONSE; NEUTRALIZATION; INFANTS; VP7; ANTIBODY; SEROTYPE; STRAIN AB The humoral and cellular immune response after symptomatic, primary rotavirus infection was examined in 8 children <2 years old. Rotavirus-specific IgA, rotavirus-specific helper T (T(h)) cells, and neutralizing antibody responses were evaluated at the time of illness, 2-8 weeks later, and 3-5 months later. In addition, rotavirus strains associated with infection were tested by polymerase chain reaction analysis using oligonucleotide primers specific for genes 4 (P type) and 9 (G type). The absence of rotavirus-specific IgA or rotavirus-specific helper T cell activity at the time of illness was consistent with a primary infection in 7 of 8 children. Two children were infected with serotype 1 (P type 1, G type 1), 3 with serotype 3 (P type 1, G type 3), and 3 with serotype 4 (P type 1, G type 4) strains. Neutralizing antibodies were directed against the gene 4 (P type) protein product (vp4). Because all infecting strains were P type 1, convalescent antisera did not distinguish among different rotavirus G types. Rotavirus-specific IgA responses were detected in 6 of 8 and rotavirus-specific T(h) cell responses in 7 of 8 children during convalescence. C1 CHILDRENS HOSP,DIV GASTROENTEROL & NUTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. US FDA,DEPT HLTH & HUM SERV,WASHINGTON,DC 20204. RP OFFIT, PA (reprint author), CHILDRENS HOSP,DIV ALLERGY IMMUNOL & INFECT DIS,34TH ST & CIV CTR BLVD,PHILADELPHIA,PA 19104, USA. RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 FU NIAID NIH HHS [AI-00889, AI-26251]; NIDDK NIH HHS [DK-07066] NR 17 TC 33 Z9 36 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 1993 VL 167 IS 6 BP 1436 EP 1440 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LD694 UT WOS:A1993LD69400029 PM 8388906 ER PT J AU BALA, S FAILLA, ML AF BALA, S FAILLA, ML TI COPPER REPLETION RESTORES THE NUMBER AND FUNCTION OF CD4 CELLS IN COPPER-DEFICIENT RATS SO JOURNAL OF NUTRITION LA English DT Article DE INTERLEUKIN-2; MITOGENIC REACTIVITY; CD4 CELLS; COPPER DEFICIENCY; RATS ID ADULT MICE; RESPONSIVENESS; NEUTROPHILS; IMPAIRMENT AB Dietary copper deficiency decreases the number of splenic CD4 cells and mitogen-induced generation of interleukin-2 activity and DNA synthesis in cultures of splenic mononuclear cells. To determine the reversibility of these defects, Cu-deficient rats were fed a Cu-adequate diet for either 4, 7 or 11 d before preparation of cell cultures. Serum and hepatic concentrations of Cu attained 87 and 75%, respectively, of the control level after 4 d of dietary repletion. In contrast, interleukin-2 activity and [H-3]thymidine incorporation in splenic cell cultures treated with T-cell mitogens were significantly greater than in cultures from Cu-deficient rats after 7, but not 4, d of dietary Cu repletion. The number of splenic CD4 cells was also greater after 7 d of dietary supplementation with Cu. Changes in the relative percentage and function of T-helper cells were highly correlated with one another and with hepatic Cu concentration. These observations indicate that an inadequate supply of dietary Cu reversibly suppresses the maturation and function of splenic T-helper cells. C1 UNIV N CAROLINA,DEPT FOOD NUTR & FOOD SERV MANAGEMENT,AU PK BLDG,GREENSBORO,NC 27412. USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE HUMAN NUTR RES CTR,VITAMIN & MINERAL NUTR LAB,BELTSVILLE,MD 20705. US FDA,DIV EVALUAT ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. NR 30 TC 22 Z9 25 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 JUN PY 1993 VL 123 IS 6 BP 991 EP 996 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LF086 UT WOS:A1993LF08600002 PM 8099369 ER PT J AU ADAMS, AM AF ADAMS, AM TI ESTABLISHING JURISDICTION THROUGH FORENSIC PARASITOLOGY SO JOURNAL OF PARASITOLOGY LA English DT Editorial Material RP ADAMS, AM (reprint author), US FDA,SEAFOOD PROD RES CTR,POB 3012,22201 23RD DR SE,BOTHELL,WA 98041, USA. NR 8 TC 3 Z9 3 U1 1 U2 4 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD JUN PY 1993 VL 79 IS 3 BP 459 EP 460 DI 10.2307/3283590 PG 2 WC Parasitology SC Parasitology GA LG095 UT WOS:A1993LG09500028 PM 8501610 ER PT J AU BROWN, ND LEADER, H PHILLIPS, LR SMEJKAL, RM GORDON, RK CHIANG, PK AF BROWN, ND LEADER, H PHILLIPS, LR SMEJKAL, RM GORDON, RK CHIANG, PK TI SYNTHESIS AND ANTIMUSCARINIC ACTIVITY OF 2-[N-(ETHYL)-(N-BETA-HYDROXYETHYL)]AMINOETHYL 2,2-DIPHENYLPROPIONATE, A METABOLITE OF APROPHEN SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID RECEPTOR AB The preparation of 2-[N-(ethyl)-(N-beta-hydroxyethyl)]amino-ethyl 2,2-diphenylpropionate (1), a metabolite of aprophen [2-diethylamineothyl 2,2-diphenylpropionate], is described. Hydrolysis of [2-(2-chloroethyl)ethylamino]ethyl acetate hydrochloride (2) in a basic solution, followed by acidic pH adjustment, gave the ethylcholineaziridinium ion (3) that upon treatment with 2,2-diphenylpropionic acid produced 1 in a 56% yield. Synthetic 1 was found to possess antimuscarinic activities, but was approximately 10-fold less potent than the parent compound aprophen. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20014. ISRAEL INST BIOL RES,IL-70450 NESS ZIONA,ISRAEL. RP BROWN, ND (reprint author), WALTER REED ARMY INST RES,APPL BIOCHEM BRANCH,WASHINGTON,DC 20307, USA. NR 12 TC 0 Z9 0 U1 0 U2 1 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 1993 VL 82 IS 6 BP 563 EP 564 DI 10.1002/jps.2600820603 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA LE459 UT WOS:A1993LE45900002 PM 8331525 ER PT J AU REGAN, PM MARGOLIN, AB WATKINS, WD AF REGAN, PM MARGOLIN, AB WATKINS, WD TI EVALUATION OF MICROBIAL INDICATORS FOR THE DETERMINATION OF THE SANITARY QUALITY AND SAFETY OF SHELLFISH SO JOURNAL OF SHELLFISH RESEARCH LA English DT Article DE MALE-SPECIFIC BACTERIOPHAGE; POLIOVIRUS AND HYBRIDIZATION PROBE ID MOLLUSCAN SHELLFISH; ESCHERICHIA-COLI; NORWALK VIRUS; ENUMERATION; OUTBREAKS; GASTROENTERITIS; BACTERIOPHAGES; BACTERIA; WATER; CLAM AB Shellfish consumed either raw or partially cooked have been implicated in the transmission of viral gastroenteritis and hepatitis A. The effectiveness of bacterial indicators to signal the presence of human pathogenic viruses has been questioned. Earlier viral assays made it impractical to monitor shellfish for viral contaminants. There exists a need for rapid and sensitive assays for human enteric viruses to ensure the sanitary quality of shellfish. Sample collections of hard-shell clams (Mercenaria mercenaria) were taken from approved, conditionally approved and prohibited shellfishing areas in Narragansett Bay, Rhode Island between July 1989 and May 1990. Clams were assayed for poliovirus and other microbial indicators (total coliforms, fecal coliforms, Clostridium perfringens, enterococci and male-specific bacteriophage) to evaluate their usefulness as viral indicators. Of these indicators, bacteriophage were most consistently recovered from each of the collection areas, and enterococci were recovered with the least frequency. Polovirus was detected in clams from the conditionally approved and prohibited area primarily during the fall and winter months. On one occasion in the prohibited area, the coliform standards for water and shellfish were not exceeded, although poliovirus was detected by a hybridization probe assay. A viral indicator system based on bacteriophage levels would require further development and evaluation to determine the correlation of specific human enteric viruses and phage. New advances in nucleic acid technology may soon enable routine monitoring of shellfish for enteric viruses. C1 UNIV NEW HAMPSHIRE,DEPT MICROBIOL,DURHAM,NH 03824. US FDA,NE TECH SERV UNIT,N KINGSTOWN,RI 02852. RP REGAN, PM (reprint author), US FDA,WINCHESTER ENGN & ANALYT CTR,WINCHESTER,MA 01890, USA. NR 31 TC 5 Z9 6 U1 1 U2 4 PU NATL SHELLFISHERIES ASSOC PI SOUTHAMPTON PA C/O DR. SANDRA E. SHUMWAY, NATURAL SCIENCE DIVISION, SOUTHAMPTON COLLEGE, SOUTHAMPTON, NY 11968 SN 0730-8000 J9 J SHELLFISH RES JI J. Shellfish Res. PD JUN PY 1993 VL 12 IS 1 BP 95 EP 100 PG 6 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA LL853 UT WOS:A1993LL85300016 ER PT J AU WELLSTOOD, SA AF WELLSTOOD, SA TI DIAGNOSTIC MYCOBACTERIOLOGY - CURRENT CHALLENGES AND TECHNOLOGIES SO LABORATORY MEDICINE LA English DT Article AB Tuberculosis (TB) has reemerged as a major public health problem worldwide. Although traditional acid-fast smears and cultures remain important tools for laboratory diagnosis of TB, these methods are not adequate to meet the challenges of the current crisis. In response to urgent needs for more rapid and sensitive diagnostic methods in mycobacteriology, several innovative procedures have been developed. Radiometric, molecular, biochemical, and chromatographic techniques have been introduced successfully in clinical laboratories, and others continue to be investigated. I review the newer technologies that provide laboratories with the tools necessary to achieve rapid detection, identification, and susceptibility testing of Mycobacterium tuberculosis. RP WELLSTOOD, SA (reprint author), USFDA,HFM-310,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 SN 0007-5027 J9 LAB MED JI Lab. Med. PD JUN PY 1993 VL 24 IS 6 BP 357 EP 361 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA LD061 UT WOS:A1993LD06100009 ER PT J AU REEVES, JP EPSTEIN, SL AF REEVES, JP EPSTEIN, SL TI RECOMBINANT HUMAN CD4 ELICITS ANTIBODY-RESPONSES DIFFERENT IN EPITOPE SPECIFICITY FROM THOSE THAT CELLULAR CD4 ELICITS SO MOLECULAR IMMUNOLOGY LA English DT Article ID T-CELLS; SOLUBLE CD4; BINDING; VIRUS; HIV; AUTOANTIBODIES; IMMUNOGLOBULIN; INDIVIDUALS; MUTANTS; INVIVO AB Recombinant proteins have been proposed as subunit vaccines for many viral, bacterial and parasitic diseases, to reduce adverse side effects associated with inactivated or attenuated vaccines. Yet little is known about the comparative immunogenicity of recombinant proteins vs native forms present in cells or on organisms, and little is known about comparisons of the specificities of such immune responses. In another observation about differing forms of an antigen, about 10% of AIDS patients have anti-CD4 autoantibodies recognizing sites seen in recombinant CD4 (rCD4) but not present on cell surface CD4. We have analyzed antibody responses of mice to human CD4 when presented in recombinant or in cellular form. The response to the whole molecule was examined, as well as the responses to two sites within the molecule. In addition, any effect of immune response genes in the responding animal was sought, which might potentially restrict or modify any response to CD4. Mice immunized with rCD4 generated a large response to rCD4, but a lower response to the cell surface form, implying that additional sites are recognized on the recombinant form that are not recognized in the cellular form. Mice immunized with cells containing surface CD4 had high titers of antibody reactive with whole cells, of which only a small portion was reactive with rCD4. Titers on rCD4 are much lower for these mice than in rCD4-immunized mice. Both forms of CD4 induced antibodies to the gp120 binding site with comparable efficiency. For another site in domain 3 or 4 of CD4, cellular CD4 induced antibodies more frequently than the recombinant form. Immune response gene differences did not play a detectable role in the anti-CD4 response. RP REEVES, JP (reprint author), US FDA,CTR BIOLOG EVALUAT & RES,DIV BIOCHEM & BIOPHYS,MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUN PY 1993 VL 30 IS 8 BP 765 EP 773 DI 10.1016/0161-5890(93)90148-5 PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA LE171 UT WOS:A1993LE17100008 PM 7684821 ER PT J AU GOERING, PL AF GOERING, PL TI LEAD-PROTEIN INTERACTIONS AS A BASIS FOR LEAD TOXICITY SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 9TH INTERNATIONAL NEUROTOXICOLOGY CONF CY OCT 28-31, 1991 CL LITTLE ROCK, AR SP NIEHS, AGCY TOX SUBST & DIS, REGISTRY, US EPA, HLTH EFFECTS RES LAB, US FDA, NATL CTR TOXICOL RES DE LEAD-PROTEIN INTERACTIONS; LEAD-BINDING PROTEINS; METALLOTHIONEIN; CARBONIC ANHYDRASE; PROTEIN KINASE-C; CALMODULIN; NUCLEIC ACID BINDING PROTEINS ID DELTA-AMINOLEVULINIC-ACID; LOW-MOLECULAR WEIGHT; BOVINE CARBONIC-ANHYDRASE; TRANSCRIPTION FACTOR-IIIA; ZINC-BINDING DOMAINS; KINASE-C; RAT-LIVER; DEHYDRATASE INHIBITION; ACTIVE-SITE; METAL-IONS AB The interaction of lead (Pb) with proteins may represent a fundamental mechanism by which Pb exerts toxicity. In this overview, various factors which influence the interaction of Pb with proteins will be discussed. Pb interacts with enzyme functional groups, and high-affinity metal-binding proteins, such as Pb-binding proteins and metallothioneins, can mediate this Pb-enzyme interaction. Many other factors influence Pb-protein interactions including ligand competition and binding affinities; protein folding and the nature of the metal-binding site; rates of protein synthesis and degradation; and intracellular localization of the ligand and metal. The remainder of this overview will focus on specific examples of important proteins known to be influenced by Pb or which hypothetically may be influenced by Pb. Gaps in knowledge and important research needs are emphasized. Many of the factors discussed play a role in the relative sensitivity of various enzymes in heme biosynthesis to Pb. Disruption of this critical pathway by Pb may result in neuropathologies and accumulation of neurotoxic heme precursors. High-affinity metal-binding proteins have been shown to play a role in mediating Pb inhibition of the octameric Zn-containing enzyme, ALA dehydratase. Knowledge of regional localization in brain and the postnatal ontogeny of the high-affinity metal-binding proteins may be pivotal in understanding Pb neurotoxicity. Other specific examples related to or potentially related to Pb toxicity which are discussed include nucleic acid binding proteins, calmodulin, protein kinase C, and carbonic anhydrase. These proteins will serve as models to understand some basic principles and differences in Pb-protein interactions.. (C) 1993 Intox Press, Inc. RP GOERING, PL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH OFF SCI & TECHNOL,DIV LIFE SCI,HFZ 112,ROCKVILLE,MD 20857, USA. NR 79 TC 166 Z9 173 U1 2 U2 9 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SUM-FAL PY 1993 VL 14 IS 2-3 BP 45 EP 60 PG 16 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA LY949 UT WOS:A1993LY94900006 PM 8247411 ER PT J AU GODAR, DE THOMAS, DP MILLER, SA LEE, W AF GODAR, DE THOMAS, DP MILLER, SA LEE, W TI LONG-WAVELENGTH UVA RADIATION INDUCES OXIDATIVE STRESS, CYTOSKELETAL DAMAGE AND HEMOLYSIS SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ULTRAVIOLET-LIGHT; LIPID-PEROXIDATION; ESCHERICHIA-COLI; NEAR-ULTRAVIOLET; 365 NM; DNA; CELLS; INVOLVEMENT; INDUCTION; PROTEIN AB We investigated the ability of the different wavelength regions of UV radiation, UVA (320-400 nm), UVB (290-320 nm) and UVC (200-290 nm), to induce hemolysis. Sheep erythrocytes were exposed to radiation from either a UVA1 (>340 nm) sunlamp, a UVB sunlamp, or a UVC germicidal lamp. The doses used for the three wavelength regions were approximately equilethal to the survival of L5178Y murine lymphoma cells. Following exposure, negligible hemolysis was observed in the UVB- and UVC-irradiated erythrocytes, whereas a decrease in the relative cell number (RCN), indicative of hemolysis, was observed in the UVA1-exposed samples. The decrease in RCN was dependent on dose (0-1625 kJ/ml), time (0-78 h postirradiation) and cell density (10(6)-10(7) cells/mL). Hemolysis decreased with increasing concentration of glutathione, hemoglobin or cell number, while the presence of pyruvate drastically enhanced it. Because scanning spectroscopy (200-700 nm) showed that hemoproteins and nicotinamide adenine dinucleotides were oxidized, cytoplasmic oxidative stress was implicated in the lytic mechanism. Further evidence of oxidation was obtained from electron micrographs, which revealed the formation of Heinz bodies near the plasma membrane. The data demonstrate that exposure of erythrocytes to UVA1, but not UVB or UVC, radiation causes oxidation of cytoplasmic components, which results in cytoskeletal damage and hemolysis. RP GODAR, DE (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857, USA. FU FDA HHS [FDA 223-88-6076] NR 51 TC 46 Z9 47 U1 1 U2 6 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1993 VL 57 IS 6 BP 1018 EP 1026 DI 10.1111/j.1751-1097.1993.tb02965.x PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LL336 UT WOS:A1993LL33600016 PM 8367531 ER PT J AU DOERGE, DR BAJIC, S LOWES, S AF DOERGE, DR BAJIC, S LOWES, S TI ANALYSIS OF CLENBUTEROL IN HUMAN PLASMA USING LIQUID-CHROMATOGRAPHY ATMOSPHERIC-PRESSURE CHEMICAL-IONIZATION MASS-SPECTROMETRY SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID BETA-AGONIST; CIMATEROL; URINE AB Clenbuterol is a beta-agonist drug used illegally as a growth stimulant in meat-producing animals and human athletes. The analysis of clenbuterol in spiked human plasma was performed using on-line liquid chromatography/atmospheric-pressure chemical-ionization mass spectrometry (LC/APCI-MS) using a conventional bore LC column (flow rate = 1.0 mL/min). At low sampling cone voltages, the mass spectrum was predominantly the [M + H]+ ion but diagnostic fragment ions were formed upon incremental increases in sampling cone voltage. The detection limit (signal-to-noise ratio of 3) using selected-ion monitoring of the [M + H]+ ion was 0.1 ng on-column (10 ppb). This is a 50-fold better sensitivity of detection than that previously reported for an on-line thermospray LC/MS method. The extraction procedures were not optimized for maximum sensitivity and the lack of interferences suggests that much lower detection limits for clenbuterol in plasma are attainable. C1 VG BIOTECH LTD,FISONS INSTRUMENTS,ALTRINCHAM WA14 5RZ,CHESHIRE,ENGLAND. RP DOERGE, DR (reprint author), NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 12 TC 36 Z9 37 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD JUN PY 1993 VL 7 IS 6 BP 462 EP 464 DI 10.1002/rcm.1290070612 PG 3 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA LH494 UT WOS:A1993LH49400011 PM 8329767 ER PT J AU BLOOM, RA MATHESON, JC AF BLOOM, RA MATHESON, JC TI ENVIRONMENTAL ASSESSMENT OF AVERMECTINS BY THE UNITED-STATES-FOOD-AND-DRUG-ADMINISTRATION SO VETERINARY PARASITOLOGY LA English DT Article; Proceedings Paper CT INVITATIONAL WORKSHOP ON ENVIRONMENTAL IMPACT OF AVERMECTIN USAGE IN LIVESTOCK CY APR 06-10, 1992 CL COLUMBUS, OH SP OHIO STATE UNIV, COMMONWEALTH SCI & IND RES ORG, DIV ENTOMOL, AUSTR DEPT TECHNOL IND & COMMERCE ID IVERMECTIN; CATTLE AB The Center of Veterinary Medicine (CVM) of the Food and Drug Administration (FDA) is required under the National Environmental Policy Act (NEPA) to include in its decision making, an objective consideration of the potential environmental impacts associated with each contemplated action. As part of the application process for new animal drugs, detailed data must be submitted in order to develop a prediction of the environmental fate and effects of the drug and/or its active metabolites. Ivermectin (22,23-dihydroavermectin B] ) is a highly active antiparasitic animal drug utilized in a variety of injectable, oral and topical formulations. Residues of this drug may reach the environment through manufacturing and animal wastes and may potentially have effects on terrestrial and aquatic organisms. A comprehensive data base has been submitted to the FDA in support of the environmental assessments for ivermectin drug products. Detailed information has been submitted on the physical and chemical properties, introduction, fate and effects of the ivermectins in the environment. These data indicate that ivermectin binds tightly to soil and is subject to photodegradation and biotransformation to less active compounds. In contrast, ivermectin is highly toxic to certain aquatic organisms but would not be expected to partition into the aquatic environment. Much lower toxicity has been demonstrated toward bacteria, fungi, earthworms, plants and birds. CVM evaluated ivermectin products based on the use pattern of the product, the metabolism pattern in target animals, calculations of potential ivermectin residue concentrations in the environment and data on persistence, soil sorption and acute toxicity in aquatic and terrestrial environments. C1 US FDA,CTR VET MED,DIV TOXICOL & ENVIRONM SCI,WASHINGTON,DC 20204. NR 12 TC 40 Z9 49 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4017 J9 VET PARASITOL JI Vet. Parasitol. PD JUN PY 1993 VL 48 IS 1-4 BP 281 EP 294 DI 10.1016/0304-4017(93)90163-H PG 14 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA LJ713 UT WOS:A1993LJ71300025 PM 8346641 ER PT J AU JOHANNESSEN, JN VERITY, MA AF JOHANNESSEN, JN VERITY, MA TI MARKERS OF NEURONAL INJURY AND DEGENERAT - PREFACE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Editorial Material C1 US FDA, CFSAN, DIV TOXICOL RES, LAUREL, MD 20708 USA. UNIV CALIF LOS ANGELES, MED CTR, DIV NEUROPATHOL, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, MED CTR, BRAIN RES INST, LOS ANGELES, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD MAY 28 PY 1993 VL 679 BP R11 EP R12 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG188 UT WOS:A1993LG18800001 ER PT J AU WEAVER, JL SZABO, G PINE, PS GOTTESMAN, MM GOLDENBERG, S ASZALOS, A AF WEAVER, JL SZABO, G PINE, PS GOTTESMAN, MM GOLDENBERG, S ASZALOS, A TI THE EFFECT OF ION-CHANNEL BLOCKERS, IMMUNOSUPPRESSIVE AGENTS, AND OTHER DRUGS ON THE ACTIVITY OF THE MULTIDRUG TRANSPORTER SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID P-GLYCOPROTEIN; MEMBRANE-POTENTIALS; CYCLOSPORIN-A; RESISTANCE; VERAPAMIL; CELLS; REVERSAL; ANALOGS; LYMPHOCYTES; VINCRISTINE AB The MDRI protein is an energy-dependent transport protein responsible for the multi-drug resistance seen in many tumors. A variety of drugs have been shown to inhibit the function of this pump, including compounds known to block various ion channels. The mouse lymphoma cell line L5178Y has been transduced with the human mdrI gene. Using this cell line, we have tested a number of compounds to determine whether there is a correlation between the ability to block a specific type of ion channel, or shift membrane potential, and the ability to act as an MDR-reversing agent using the fluorescent substrates Rhodamine 123 and daunorubicin as test compounds. Our results show no apparent correlation between the ability to block a specific ion channel and reversal of MDR transport ability. We have found active MDR inhibitors in compounds that affect K+, Na+, Ca++, H+, but not Cl- channels. Our data suggest that Cl-channel activity may be distinct from MDR activity. Several immunosuppressive compounds and analogs were also tested and found to be active reversing agents. Measurements suggest a significant difference in resting membrane potential between the L5178YvMDR line and the L5178Y parental cell line used in these experiments. No correlation was found between the ability of drugs to alter membrane potential and to inhibit MDR transport activity. Our results suggest that MDR transport function may be independent of the physiological movement of ions and show that a wide variety of compounds can inhibit MDR transport. C1 US FDA,CDER,DIV RES & TESTING,HFD-471,200 C ST SW,WASHINGTON,DC 20204. DEBRECEN UNIV MED,SCH MED,DEPT BIOPHYS,H-4012 DEBRECEN,HUNGARY. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 31 TC 105 Z9 105 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 28 PY 1993 VL 54 IS 3 BP 456 EP 461 DI 10.1002/ijc.2910540317 PG 6 WC Oncology SC Oncology GA LE893 UT WOS:A1993LE89300016 PM 7685326 ER PT J AU HALPERN, JL LOFTUS, A AF HALPERN, JL LOFTUS, A TI CHARACTERIZATION OF THE RECEPTOR-BINDING DOMAIN OF TETANUS TOXIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGHT CHAIN; POLYPEPTIDE FRAGMENTS; INHIBITS EXOCYTOSIS; BOTULINUM TOXINS; BRAIN MEMBRANES; CELLS; GANGLIOSIDES; EXPRESSION; LOCALIZATION; NEUROTOXINS AB The carboxyl-terminal half of the heavy chain of tetanus toxin (H(C)) contains the domain required for binding to purified gangliosides and neuronal cells. The structural requirements for the interaction of H(C) with receptor were studied by generating mutants of H(C) with deletions at either the carboxyl or amino terminus and characterizing their binding. A deletion of 10 or more amino acids from the carboxyl terminus resulted in a major loss of H(C) binding to purified gangliosides and spinal cord neuronal cells, whereas a deletion of the carboxyl-terminal 5 amino acids did not affect binding. The removal of up to 263 amino acids from the amino terminus did not inhibit binding. Each of the truncated proteins was much more sensitive to trypsin than was full-length H(C), suggesting an alteration in conformation. The receptor binding activity of H(C) was not retained in a peptide corresponding to the carboxyl-terminal 20 amino acids. These data suggest that the carboxyl-terminal region of H(C) is important for maintaining a conformation necessary for binding to receptor. RP HALPERN, JL (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BLDG 29,RM 103,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 85 Z9 88 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1993 VL 268 IS 15 BP 11188 EP 11192 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD466 UT WOS:A1993LD46600070 PM 8388386 ER PT J AU ALI, SF HOLSON, RR NEWPORT, GD SLIKKER, W BOWYER, JF AF ALI, SF HOLSON, RR NEWPORT, GD SLIKKER, W BOWYER, JF TI DEVELOPMENT OF DOPAMINE AND N-METHYL-D-ASPARTATE SYSTEMS IN RAT-BRAIN - THE EFFECT OF PRENATAL PHENCYCLIDINE EXPOSURE SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE PHENCYCLIDINE; GESTATIONAL EXPOSURE; DOPAMINE; RELEASE; NMDA RECEPTOR COMPLEX; DEVELOPMENT ID STRIATAL SLICES; GESTATIONAL EXPOSURE; CAUDATE-PUTAMEN; EVOKED RELEASE; BINDING-SITES; FETAL BRAIN; L-GLUTAMATE; AMPHETAMINE; RECEPTORS; PCP AB Phencyclidine (PCP) inhibits the uptake of the neurotransmitter dopamine (DA), and blocks N-methyl-D-aspartate (NMDA) receptor-regulated ion channels. PCP also binds to sigma receptors in vivo and in vitro in rat brain. Prolonged exposure to PCP in adults has been observed to reduce the number of PCP binding sites in brain. We designed these experiments to evaluate whether prolonged prenatal exposure to PCP produces alterations in the development of DA and NMDA systems in brain. To do so, we characterized the normal course of development of basal and stimulated DA release in striatal slices, the ontogeny of striatal DA concentrations, and the development of NMDA receptor channels and associated glutamate binding sites in frontal cortex. We compared these developmental profiles to those in rats exposed to prenatal PCP, in an attempt to characterize the effect of prenatal PCP exposure on the pattern of brain development. Pregnant CD rats were injected s.c. with either 0, 10 or 20 mg/kg PCP daily on gestational days 8 through 20. On postnatal days (PND) 8, 21, 45, or 100, rats were sacrificed and brain tissues isolated for in vitro assessment. In vitro [H-3]E)A release from striatal slices evoked by either 40 muM glutamate or 15 mM K+ increased over 250% from PND 8 to PND 45, and glutamate-stimulated release was still significantly below adult levels at PND 45. In contrast, D-methamphetamine (D-METH)-evoked [H-3]DA release, frontal cortical glutamate binding sites and NMDA channels developed early, reaching adult levels on or before PND 21. At PND 8 but not thereafter prenatal PCP (10 or 20 mg/kg) appeared to increase glutamate-evoked [H-3]DA release but not K+- and METH-evoked release in striatal slices. There were no significant effects of prenatal PCP exposure on the in vivo levels of DA or serotonin or their metabolites in striatum at any PND. PCP exposure also had no effect on the NMDA receptor ion channel or the glutamate binding site in frontal cortex at any age. These data indicate that prenatal exposure to PCP may selectively but transiently and moderately change glutamate evoked DA release early in development without affecting the in vivo levels of DA and serotonin or NMDA receptor complex levels in developing brain. C1 UNIV ARKANSAS MED SCI HOSP, DEPT PHARMACOL & TOXICOL, LITTLE ROCK, AR 72205 USA. UNIV ARKANSAS MED SCI HOSP, DEPT BIOCHEM & MOLEC BIOL, LITTLE ROCK, AR 72205 USA. RP ALI, SF (reprint author), NATL CTR TOXICOL RES, DIV NEUROTOXICOL, NEUROCHEM LAB, HFT-132, NCTR DR, JEFFERSON, AR 72079 USA. NR 61 TC 18 Z9 18 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD MAY 21 PY 1993 VL 73 IS 1 BP 25 EP 33 DI 10.1016/0165-3806(93)90042-9 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA LC008 UT WOS:A1993LC00800004 ER PT J AU ERNEY, DR GILLESPIE, AM GILVYDIS, DM POOLE, CF AF ERNEY, DR GILLESPIE, AM GILVYDIS, DM POOLE, CF TI EXPLANATION OF THE MATRIX-INDUCED CHROMATOGRAPHIC RESPONSE ENHANCEMENT OF ORGANOPHOSPHORUS PESTICIDES DURING OPEN-TUBULAR COLUMN GAS-CHROMATOGRAPHY WITH SPLITLESS OR HOT ON-COLUMN INJECTION AND FLAME PHOTOMETRIC DETECTION SO JOURNAL OF CHROMATOGRAPHY LA English DT Article ID RESIDUE DETERMINATION; EXTRACTS; CLEANUP AB The observed chromatographic response for organophosphorus pesticides in extracts from milk and butterfat is shown to matrix dependent. The matrix protects the organophosphorus compounds from adsorption and/or decomposition in hot vaporizing injectors ensuring a more complete transfer from injector to column compared to the results observed when standards dissolved in matrix-free solvent are used. This results in recoveries in excess of 100% for residue-free extracts spiked with organophosphorus pesticides when standards prepared in residue-free solvents are used for calibration. The chromatographic response enhancement is minimized by using hot on-column injection at an optimized injection temperature, but not completely eliminated. The preferred method of calibration is to use matrix standard solutions prepared by adding known amounts of organophosphorus pesticides to residue-free sample matrix of the same character and in similar concentration to the samples to be analyzed. C1 US FDA,PESTICIDES & IND CHEM RES CTR,1560 E JEFFERSON AVE,DETROIT,MI 48207. WAYNE STATE UNIV,DEPT CHEM,DETROIT,MI 48202. NR 15 TC 240 Z9 262 U1 2 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD MAY 21 PY 1993 VL 638 IS 1 BP 57 EP 63 DI 10.1016/0021-9673(93)85007-T PG 7 WC Chemistry, Analytical SC Chemistry GA LE006 UT WOS:A1993LE00600007 ER PT J AU MIDLAND, SL KEEN, NT SIMS, JJ MIDLAND, MM STAYTON, MM BURTON, V SMITH, MJ MAZZOLA, EP GRAHAM, KJ CLARDY, J AF MIDLAND, SL KEEN, NT SIMS, JJ MIDLAND, MM STAYTON, MM BURTON, V SMITH, MJ MAZZOLA, EP GRAHAM, KJ CLARDY, J TI THE STRUCTURES OF SYRINGOLIDE-1 AND SYRINGOLIDE-2, NOVEL C-GLYCOSIDIC ELICITORS FROM PSEUDOMONAS-SYRINGAE PV TOMATO SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; AVIRULENCE GENE D; PRODUCE AB The isolation and structure determination of two bacterial signal molecules which elicit active plant defense responses are reported. The production of these molecules by Gram-negative bacteria requires the action of a virulence gene D (avrD), cloned from Pseudomonas syringae pv. tomato. The structures of syringolide 1 (1a) and syringolide 2 (1b) are determined by a combination of NMR experiments, biosynthetic arguments, molecular modeling, and X-ray crystallography. A proposed biosynthetic scheme based on the condensation of D-xylulose with a beta-ketoalkanoic acid is presented. Further cyclization of the biosynthetic intermediates leads to C-glycosides with a novel tricyclic ring system. These are the first nonproteinaceous specific elicitors of a plant hypersensitive response. C1 UNIV CALIF RIVERSIDE,DEPT PLANT PATHOL,RIVERSIDE,CA 92521. UNIV CALIF RIVERSIDE,DEPT CHEM,RIVERSIDE,CA 92521. UNIV WYOMING,DEPT MOLEC BIOL,LARAMIE,WY 82071. US FDA,NAT PROD INSTRUMENTAT BRANCH,WASHINGTON,DC 20204. CORNELL UNIV,BAKER LAB,DEPT CHEM,ITHACA,NY 14853. NR 31 TC 104 Z9 104 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAY 21 PY 1993 VL 58 IS 11 BP 2940 EP 2945 DI 10.1021/jo00063a007 PG 6 WC Chemistry, Organic SC Chemistry GA LD262 UT WOS:A1993LD26200007 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI HAEMOPHILUS-B CONJUGATE VACCINE (TETANUS TOXOID CONJUGATE) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 19 PY 1993 VL 269 IS 19 BP 2491 EP 2491 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LB450 UT WOS:A1993LB45000007 PM 8487398 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI DENTAL AMALGAM REPORT ISSUED SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 19 PY 1993 VL 269 IS 19 BP 2491 EP 2491 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LB450 UT WOS:A1993LB45000005 PM 8487398 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI 2 NEW CHILD VACCINES LICENSED - COMBINATION DTP AND HAEMOPHILUS-B CONJUGATE VACCINE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP NIGHTINGALE, SL (reprint author), US FDA,OFF HLTH AFFAIRS,PARKLAWN BLDG,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 19 PY 1993 VL 269 IS 19 BP 2491 EP 2491 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LB450 UT WOS:A1993LB45000006 PM 8487398 ER PT J AU DOERGE, DR AF DOERGE, DR TI ISOTOPE-DILUTION LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY USING A PARTICLE-BEAM INTERFACE SO ANALYTICAL CHEMISTRY LA English DT Letter RP DOERGE, DR (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 15 PY 1993 VL 65 IS 10 BP 1489 EP 1490 DI 10.1021/ac00058a031 PG 2 WC Chemistry, Analytical SC Chemistry GA LC098 UT WOS:A1993LC09800032 ER PT J AU IWAI, Y AKAHANE, K PLUZNIK, DH COHEN, RB AF IWAI, Y AKAHANE, K PLUZNIK, DH COHEN, RB TI CA2+ IONOPHORE A23187-DEPENDENT STABILIZATION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR MESSENGER-RNA IN MURINE THYMOMA EL-4 CELLS IS MEDIATED THROUGH 2 DISTINCT REGIONS IN THE 3'-UNTRANSLATED REGION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; 3' UNTRANSLATED REGION; PROTEIN KINASE-C; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; SIGNAL TRANSDUCTION; DNA; DEGRADATION; LYMPHOCYTES; IDENTIFICATION AB We analyze the role of the Ca2+ ionophore A23187 in the induction of GM-CSF mRNA expression in EL-4 thymoma cells. Northern analysis shows that A23187 increases the half-life of GM-CSF mRNA. To identify potential Ca2+ response elements in the GM-CSF mRNA, we produced stable transfectants containing pRSV-CAT (EL-4cat) or hybrid constructs in which most of the GM-CSF 3'-untranslated region (EL-4gm) or the adenosine-uridine boxes alone (EL-4au) were placed in a downstream position from the CAT coding region. A23187 induces a 4.4-fold increase in CAT activity in EL-4cat cells and a 210-fold and 48-fold increase in CAT activity in EL-4gm and EL-4au cells, respectively. Actinomycin D chase experiments in transfected cells demonstrate that A23187 increases the half-life of CAT mRNA from 15 min to 3 h in EL-4au cells and more than 3 h in EL-4gm cells, suggesting that the effect of Ca2+ is mediated predominantly by the adenosine-uridine boxes with a smaller contribution from upstream regions. To map these upstream regions, we transfected cells with constructs containing mutations of the 3'-untranslated region. With two of these mutations, corresponding to a region located about 160 bases upstream of the adenosine-uridine boxes, CAT activity was induced only 50-fold compared to 200-fold in EL-4gm cells. These data indicate that two regions within the GM-CSF 3'-untranslated region interact to modulate Ca2+ effects on GM-CSF mRNA half-life. C1 US FDA,CTR BIOLOG EVALUAT & RES,DIV HEMATOL PROD,BLDG 29A,ROOM 3B-19,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 35 TC 59 Z9 59 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1993 VL 150 IS 10 BP 4386 EP 4394 PG 9 WC Immunology SC Immunology GA LB650 UT WOS:A1993LB65000022 PM 8482841 ER PT J AU EHRENREICH, H RIECKMANN, P SINOWATZ, F WEIH, KA ARTHUR, LO GOEBEL, FD BURD, PR COLIGAN, JE CLOUSE, KA AF EHRENREICH, H RIECKMANN, P SINOWATZ, F WEIH, KA ARTHUR, LO GOEBEL, FD BURD, PR COLIGAN, JE CLOUSE, KA TI POTENT STIMULATION OF MONOCYTIC ENDOTHELIN-1 PRODUCTION BY HIV-1 GLYCOPROTEIN-120 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; IMMUNE-DEFICIENCY-SYNDROME; CEREBRAL-ARTERIES; ENVELOPE PROTEIN; GLIAL-CELLS; SOLUBLE CD4; MACROPHAGES; INFECTION AB Monocytes/macrophages play a critical role in the pathogenesis of HIV infection, both as targets for virus replication and as sources of production of multifunctional cytokines. Endothelins, peptides with potent vasoconstricting activities originally isolated from endothelial cells, are also produced and secreted by macrophages in a manner similar to that of other cytokines. In an attempt to explore the potential role of endothelins in HIV-infection, we investigated the effect of the HIV-1 envelope glycoprotein, glycoprotein 120, on monocytic endothelin-1 production. This glycoprotein has been identified as a potent stimulator of monokines such as TNF-alpha and IL-6, which have been implicated as potential mediators of HIV-encephalopathy. We found that glycoprotein 120, similar to LPS, stimulates the secretion of endothelin-1, as well as TNF-alpha, from macrophages in a concentration-dependent manner. Using reverse transcriptase polymerase chain reaction, we found that circulating monocytes in HIV-infected individuals show a distinct expression of the endothelin-1 gene that is not detectable in healthy controls, indicating chronic activation of this gene in HIV-infection. In addition, cerebral macrophages in patients with HIV-encephalopathy were strongly positive for endothelin. Thus, monocytic endothelins appear to be stimulated during HIV infection. Their potent vasoactive properties render them potential candidates for mediating alterations in the cerebral perfusion pattern associated with the AIDS dementia complex. C1 NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. NIAID, CLIN INVEST LAB, BETHESDA, MD 20892 USA. NIAID, BIOL RESOURCES BRANCH, BETHESDA, MD 20892 USA. UNIV GOTTINGEN, DEPT NEUROL, W-3400 GOTTINGEN, GERMANY. UNIV GOTTINGEN, DEPT PSYCHIAT, W-3400 GOTTINGEN, GERMANY. UNIV MUNICH, MED POLIKLIN, W-8000 MUNICH 2, GERMANY. US FDA, CTR BIOLOG EVALUAT & RES, BETHESDA, MD 20014 USA. NCI, PROGRAM RESOURCES INC DYN CORP, FREDERICK, MD 21701 USA. FU NCI NIH HHS [N01-CO-74102] NR 51 TC 109 Z9 112 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 MAY 15 PY 1993 VL 150 IS 10 BP 4601 EP 4609 PG 9 WC Immunology SC Immunology GA LB650 UT WOS:A1993LB65000044 PM 8482849 ER PT J AU GUEST, GB AF GUEST, GB TI USE OF FDA-APPROVED DRUGS IN VETERINARY-MEDICINE - PROHIBITIONS, PREROGATIVES, AND RESPONSIBILITIES SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material RP GUEST, GB (reprint author), FOOD & DRUG ADM CTR VET MED,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1993 VL 202 IS 10 BP 1606 EP 1607 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA LC102 UT WOS:A1993LC10200023 ER PT J AU BANVILLE, A ZELLER BARNES, C BRUMBAUGH, G CLELAND, J RIDDELL, G POWERS, T AF BANVILLE, A ZELLER BARNES, C BRUMBAUGH, G CLELAND, J RIDDELL, G POWERS, T TI USE OF FDA-APPROVED DRUGS IN VETERINARY-MEDICINE - PROHIBITIONS, PREROGATIVES, AND RESPONSIBILITIES - QUESTIONS AND ANSWERS SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Discussion C1 TEXAS A&M UNIV SYST,COLL STN,TX 77843. AUBURN UNIV,AUBURN,AL 36849. PURDUE UNIV,W LAFAYETTE,IN 47907. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1993 VL 202 IS 10 BP 1613 EP 1617 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA LC102 UT WOS:A1993LC10200026 ER PT J AU GUEST, GB AF GUEST, GB TI FDA EXTRALABEL USE POLICY - 1992 REVISIONS SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article RP GUEST, GB (reprint author), US FDA,CTR VET MED,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1993 VL 202 IS 10 BP 1620 EP 1623 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA LC102 UT WOS:A1993LC10200028 PM 8514568 ER PT J AU POWERS, TE SUNDLOF, S RITTER, L GUEST, G POWERS, T JENKINS, W BRUNTON, J ZELLER, M MACOMBER, LE CLARK, J LOEW, F REID, J MCCARTHY, J JOHNSON, G BRUMBAUGH, G JOHNSON, DE AF POWERS, TE SUNDLOF, S RITTER, L GUEST, G POWERS, T JENKINS, W BRUNTON, J ZELLER, M MACOMBER, LE CLARK, J LOEW, F REID, J MCCARTHY, J JOHNSON, G BRUMBAUGH, G JOHNSON, DE TI USE OF FDA-APPROVED DRUGS IN VETERINARY-MEDICINE - PROHIBITIONS, PREROGATIVES, AND RESPONSIBILITIES .1. SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Discussion C1 TEXAS A&M UNIV SYST,COLL STN,TX 77843. US FDA,CVM,BETHESDA,MD 20014. LOUISIANA STATE UNIV,BATON ROUGE,LA 70803. TUFTS UNIV,BOSTON,MA 02111. RP POWERS, TE (reprint author), UNIV FLORIDA,GAINESVILLE,FL 32611, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1993 VL 202 IS 10 BP 1626 EP 1631 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA LC102 UT WOS:A1993LC10200030 ER PT J AU TESKE, RH AF TESKE, RH TI CURRENT FDA POLICY ON USE OF HUMAN-LABELED DRUGS IN ANIMALS SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article RP TESKE, RH (reprint author), US FDA,CTR VET MED,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1993 VL 202 IS 10 BP 1632 EP 1633 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA LC102 UT WOS:A1993LC10200031 PM 8514570 ER PT J AU GLOYD, J KEELING MACOMBER LEIN, D BANVILLE, A CRAWFORD BRUMBAUGH, G STRIBLING HOLT WILSON, J HUBBARD, W BRUNTON, J GINGERICH, D JOHNSON, G LUTHER, L WEISSINGER, J COPPOC, G RITTER, L AF GLOYD, J KEELING MACOMBER LEIN, D BANVILLE, A CRAWFORD BRUMBAUGH, G STRIBLING HOLT WILSON, J HUBBARD, W BRUNTON, J GINGERICH, D JOHNSON, G LUTHER, L WEISSINGER, J COPPOC, G RITTER, L TI USE OF FDA-APPROVED DRUGS IN VETERINARY-MEDICINE - PROHIBITIONS, PREROGATIVES, AND RESPONSIBILITIES .3. SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article C1 UNIV PENN,PHILADELPHIA,PA 19104. USDA,FSIS,WASHINGTON,DC 20250. STOLLE RES & DEV CORP,CINCINNATI,OH 45242. US FDA,WASHINGTON,DC 20204. PURDUE UNIV,W LAFAYETTE,IN 47907. AMER FARM BUR FEDERAT,PK RIDGE,IL 60068. CORNELL UNIV,NEW YORK STATE VET MED SOC,ITHACA,NY 14853. AMER VEAL ASSOC,NAPERVILLE,IL 60563. NATL FOOD PROCESSORS ASSOC,WASHINGTON,DC 20005. TEXAS A&M UNIV SYST,COLL VET MED,DEPT VET PHYSIOL,COLL STN,TX 77843. KING & SPALDING,WASHINGTON,DC 20006. AMER KENNEL CLUB,NEW YORK,NY 10010. MCGUINESS & WILLIAMS,WASHINGTON,DC 20005. RP GLOYD, J (reprint author), AVMA,WASHINGTON,DC, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1993 VL 202 IS 10 BP 1684 EP 1692 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA LC102 UT WOS:A1993LC10200050 ER PT J AU GEYER, RE AF GEYER, RE TI IMPLICATIONS FOR THE FDA CENTER FOR VETERINARY-MEDICINE (CVM) SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article RP GEYER, RE (reprint author), US FDA,CVM,OFF SURVEILLANCE & COMPLIANCE,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1993 VL 202 IS 10 BP 1718 EP 1719 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA LC102 UT WOS:A1993LC10200058 PM 8514592 ER PT J AU POWERS, T GEYER, RE REID, J SUNDLOF, S WILKES, D BOOTHE, D TESKE, RH BRUMBAUGH, G BROWN, S ADAMS, JB LEIN, D SWANSON, R AF POWERS, T GEYER, RE REID, J SUNDLOF, S WILKES, D BOOTHE, D TESKE, RH BRUMBAUGH, G BROWN, S ADAMS, JB LEIN, D SWANSON, R TI IMPLICATIONS FOR THE FDA CENTER FOR VETERINARY-MEDICINE (CVM) - QUESTIONS AND ANSWERS SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article C1 US FDA,CVM,OFF SURVEILLANCE & COMPLIANCE,ROCKVILLE,MD 20855. UNIV FLORIDA,GAINESVILLE,FL 32611. NATL CATTLEMENS ASSOC,RES & IND INFORMAT,ENGLEWOOD,CO 80155. TEXAS A&M UNIV SYST,COLL STN,TX 77843. UPJOHN CO,KALAMAZOO,MI 49001. CORNELL UNIV,NEW YORK STATE VET MED SOC,ITHACA,NY 14853. NATL MILK PRODUCERS FEDERAT,DIV MILK SAFETY & ANIM HLTH,ARLINGTON,VA 22201. US FDA,CTR VET MED,ROCKVILLE,MD 20855. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1993 VL 202 IS 10 BP 1720 EP 1723 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA LC102 UT WOS:A1993LC10200059 ER PT J AU TESKE, RH JOCHLE, W MONTGOMERY, A MACOMBER, LE GLOYD, JS JOCHLE AF TESKE, RH JOCHLE, W MONTGOMERY, A MACOMBER, LE GLOYD, JS JOCHLE TI USE OF FDA-APPROVED DRUGS IN VETERINARY-MEDICINE - PROHIBITIONS, PREROGATIVES, AND RESPONSIBILITIES .5. SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Discussion C1 US FDA,WASHINGTON,DC 20204. RP TESKE, RH (reprint author), US FDA,CTR VET MED,7500 STANDISH PL,ROCKVILLE,MD 20855, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD MAY 15 PY 1993 VL 202 IS 10 BP 1740 EP 1741 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA LC102 UT WOS:A1993LC10200068 ER PT J AU DEVIDAS, M GEORGE, EO ZELTERMAN, D AF DEVIDAS, M GEORGE, EO ZELTERMAN, D TI GENERALIZED LOGISTIC-MODELS FOR LOW-DOSE RESPONSE DATA SO STATISTICS IN MEDICINE LA English DT Article ID CANCER; CURVES AB We discuss a generalization of the logistic response function of the form Pr(y = 1\x) = {1 + exp(- theta - beta'x)}-alpha, where alpha > 0. This function coincides with the usual logistic response when the shape parameter a is equal to one. We describe the use of this model for analysing cancer rates in mice for low-dose exposure to a known carcinogen. When estimating the low-dose responses, the errors associated with extrapolation are reduced when a priori knowledge about the rates among unexposed individuals is incorporated into the fitting procedures. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. MEMPHIS STATE UNIV,DEPT MATH SCI,MEMPHIS,TN 38152. UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,MINNEAPOLIS,MN 55455. RP DEVIDAS, M (reprint author), UNIV CALIF LOS ANGELES,DEPT MATH,LOS ANGELES,CA 90024, USA. FU NIA NIH HHS [P01-AG08761]; NIAID NIH HHS [NCI-AI05073]; NIDCD NIH HHS [P50-DC00133] NR 29 TC 2 Z9 2 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 15 PY 1993 VL 12 IS 9 BP 881 EP 892 DI 10.1002/sim.4780120907 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA LD776 UT WOS:A1993LD77600006 PM 8327804 ER PT J AU DAVIS, M OSAKI, C GORDON, D HINDS, MW MOTTRAM, K WINEGAR, C AVNER, ED TARR, PI JARDINE, D GOLDOFT, M BARTLESON, B LEWIS, J KOBAYASHI, JM BILLMAN, G BRADLEY, J HUNT, S TANNER, P GINSBERG, M BARRETT, L WERNER, SB RUTHERFORD, GW JUE, RW ROOT, H BROTHERS, D CHEHEY, RL HUDSON, RH DIXON, FR MAXSON, DJ EMPEY, L RAVENHOLT, O UECKART, VH DISALVO, A KWALICK, DS SALCIDO, R BRUS, D AF DAVIS, M OSAKI, C GORDON, D HINDS, MW MOTTRAM, K WINEGAR, C AVNER, ED TARR, PI JARDINE, D GOLDOFT, M BARTLESON, B LEWIS, J KOBAYASHI, JM BILLMAN, G BRADLEY, J HUNT, S TANNER, P GINSBERG, M BARRETT, L WERNER, SB RUTHERFORD, GW JUE, RW ROOT, H BROTHERS, D CHEHEY, RL HUDSON, RH DIXON, FR MAXSON, DJ EMPEY, L RAVENHOLT, O UECKART, VH DISALVO, A KWALICK, DS SALCIDO, R BRUS, D TI UPDATE - MULTISTATE OUTBREAK OF ESCHERICHIA-COLI O157-H7 INFECTIONS FROM HAMBURGERS - WESTERN UNITED-STATES, 1992-1993 (REPRINTED FROM, MMWR, VOL 42, PG 258, 1993) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 SNOHOMISH HLTH DIST, EVERETT, WA USA. TACOMA PIERCE CTY HLTH DEPT, TACOMA, WA USA. UNIV WASHINGTON, SCH MED, DEPT PEDIAT, SEATTLE, WA 98195 USA. UNIV WASHINGTON, SCH MED, DEPT ANESTHESIOL, SEATTLE, WA 98195 USA. UNIV WASHINGTON, SCH MED, DEPT PEDIAT, SEATTLE, WA 98195 USA. CHILDRENS HOSP & MED CTR, SEATTLE, WA USA. CHILDRENS HOSP, SAN DIEGO, CA USA. CALIF DEPT HLTH SERV, BERKELEY, CA 94704 USA. CENT DIST HLTH DEPT, BOISE, ID USA. SW DIST HLTH DEPT, CALDWELL, ID USA. IDAHO DEPT HLTH & WELFARE, DIV HLTH, BOISE, ID USA. CLARK CTY HLTH DIST, LAS VEGAS, NV USA. US FDA, CTR FOOD SAFETY & APPL NUTR, WASHINGTON, DC 20204 USA. USDA, FOOD SAFETY INSPECT SERV, ANIM & PLANT HLTH INSPECT SERV, WASHINGTON, DC 20250 USA. CTR DIS CONTROL, DIV FIELD EPIDEMIOL, EPIDEMIOL PROGRAM OFF, ATLANTA, GA 30333 USA. CTR DIS CONTROL, NATL CTR INFECT DIS, DIV BACTERIAL & MYCOT DIS, ENTER DIS BRANCH, ATLANTA, GA 30333 USA. RP DAVIS, M (reprint author), SEATTLE KING CTY DEPT PUBL HLTH, SEATTLE, WA USA. NR 1 TC 15 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 1993 VL 269 IS 17 BP 2194 EP + PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA KZ406 UT WOS:A1993KZ40600005 ER PT J AU CARLIN, AS SIMMONS, JE ELARINI, SK SHIU, GK AF CARLIN, AS SIMMONS, JE ELARINI, SK SHIU, GK TI DETERMINATION OF KHELLIN IN SERUM BY GAS-CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS LA English DT Note AB A rapid gas chromatographic assay has been developed for the separation and determination of khellin in human serum. Using a DB-17 capillary column and a simple chloroform extraction, khellin and an internal standard, trioxsalen, were separated from endogenous substances without further clean-up. Spiked serum samples in the range 0.11-1.1 mug/ml were assayed and a linear calibration curve obtained. C1 US FDA,OFF GENER DRUGS,ROCKVILLE,MD 20855. NATL RES CTR,CAIRO,EGYPT. RP CARLIN, AS (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOPHARMACEUT,BIOPHARMACEUT RES BRANCH,HFD-424,200 C ST SW,WASHINGTON,DC 20204, USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR-BIOMED JI J. Chromatogr.-Biomed. Appl. PD MAY 5 PY 1993 VL 614 IS 2 BP 324 EP 327 DI 10.1016/0378-4347(93)80325-X PG 4 WC Chemistry, Analytical SC Chemistry GA LC091 UT WOS:A1993LC09100017 PM 8314946 ER PT J AU NOMURA, Y OKUNO, T MIZUNO, M AF NOMURA, Y OKUNO, T MIZUNO, M TI TREATMENT OF VERTIGO USING LASER LABYRINTHECTOMY SO ACTA OTO-LARYNGOLOGICA LA English DT Article; Proceedings Paper CT 1992 SCIENTIFIC CONGRESS OF THE COLLEGIUM-OTO-RHINO-LARYNGOLOGICUM - AMICTAE-SACRUM ( CORLAS ) CY NOV 01-04, 1992 CL CAIRO, EGYPT SP COLLEGIUM OTO RHINO LARYNGOL DE LASER LABYRINTHECTOMY; PERILYMPH FISTULA; BENIGN PAROXYSMAL POSITIONAL VERTIGO AB Benign paroxysmal positional vertigo developed in a patient with perilymph fistula 3 years after closure of the fistula which was in the lower margin of the annular ligament. The patient's symptoms were long-lasting and intractable. The macula utriculi and utriculoampullary nerve were irradiated by argon laser beams through the stapedectomized oval window. Singular neurectomy was performed using Argon laser, although the nerve could not be identified. After surgery, the patient's symptoms disappeared. Pure tone average of the operated side was 50 dB which remained unchanged after surgery. The macula utriculi may have been completely destroyed. Ocular counter-rolling was indicative of hypofunction of the irradiated utricle. The singular nerve may or may not have been sectioned. The ampullary nerves to the lateral canal and probably the anterior canal were intact, judging from the normal caloric reaction. C1 US BUR RADIOL HLTH,DEPT OTOLARYNGOL,ROCKVILLE,MD 20852. RP NOMURA, Y (reprint author), SHOWA UNIV,DEPT OTOLARYNGOL,SHINAGAWA KU,TOKYO 142,JAPAN. NR 9 TC 5 Z9 5 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD MAY PY 1993 VL 113 IS 3 BP 261 EP 262 DI 10.3109/00016489309135805 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA LB217 UT WOS:A1993LB21700009 PM 8100107 ER PT J AU SELVAM, MP BLAY, RA GEYER, S BUCK, SM POLLOCK, L MAYNER, RE EPSTEIN, JS AF SELVAM, MP BLAY, RA GEYER, S BUCK, SM POLLOCK, L MAYNER, RE EPSTEIN, JS TI INHIBITION OF HIV-1 REPLICATION IN H9 CELLS BY NYSTATIN-A COMPARED WITH OTHER ANTIVIRAL AGENTS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; B METHYL-ESTER; HTLV-III; LIPID-COMPOSITION; INVITRO; INFECTIVITY; AL-721; AIDS AB Nystatin A was compared in vitro with amphotericin B, AZT, or foscarnet for their respective abilities to inhibit the replication of human immunodeficiency virus type 1 (HIV-1) in H9 cells. HIV-1-infected H9 cells were cultured for 7 days in the presence of each of these drugs, at various concentrations. Reverse transcriptase activity and p24 antigen production were quantitated. Untreated, HIV-1-infected H9 cells served as the control. Nystatin A inhibited viral replication most effectively at 10 mug/ml, a concentration that did not affect cell viability. Nystatin-A treatment inhibited RT activity by 85% and p24 production by 90%. These levels of inhibition were comparable to that mediated by amphotericin B, AZT, or foscarnet at 10, 25, and 50 mug/ml, respectively. Western blot analysis of the HIV-1-infected H9 cells treated with these drugs did not detect any expression of viral proteins. These findings were further corroborated by indirect immunofluorescence studies using monoclonal anti-gp120 FITC-conjugated antibodies and by polymerase chain reaction for proviral DNA analysis, using a P-32-labeled probe. These results suggest that Nystatin A merits attention as an antiviral drug for the treatment of HIV-1 infection. In vivo drug delivery by liposome encapsulation to overcome problems of bioavailability is currently under study. RP SELVAM, MP (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,IMMUNOCHEM LAB,HFM-321,ROCKVILLE,MD 20852, USA. NR 23 TC 16 Z9 16 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 MAY PY 1993 VL 9 IS 5 BP 475 EP 481 DI 10.1089/aid.1993.9.475 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LD673 UT WOS:A1993LD67300013 PM 7686387 ER PT J AU MURRAY, EW AF MURRAY, EW TI PROBING THE SAFETY OF CENTRAL VENOUS CATHETERS SO AMERICAN JOURNAL OF NURSING LA English DT Article RP MURRAY, EW (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF TRAINING & ASSISTANCE,ROCKVILLE,MD 20857, USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD MAY PY 1993 VL 93 IS 5 BP 72 EP & PG 0 WC Nursing SC Nursing GA LB496 UT WOS:A1993LB49600027 PM 8488905 ER PT J AU RAMIREZVICK, J VARGAS, FF AF RAMIREZVICK, J VARGAS, FF TI ALBUMIN MODULATION OF PARACELLULAR PERMEABILITY OF PIG VENA-CAVAL ENDOTHELIUM SHOWS SPECIFICITY FOR PIG ALBUMIN SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ALBUMIN SPECIFICITY; ENDOTHELIAL PERMEABILITY; PIG VENA CAVA ID FROG MESENTERIC CAPILLARIES; HYDRAULIC CONDUCTIVITY; ELECTRICAL-RESISTANCE; DOG ALBUMIN; BINDING; MUSCLE; CELLS; ABSENCE; SULFATE; SITES AB We measured endothelial hydraulic conductivity (L(p,e)) and endothelial electrical resistance (R(e)) of pig vena cava in pig serum albumin (PSA) and bovine serum albumin (BSA) to determine whether specificity for the autologous albumin found in dog vena cava is a general property of mammalian endothelium. Pigs were anesthetized with pentobarbital sodium for surgical removal of the thoracic inferior vena cava. A vessel segment was placed as a membrane separating two compartments in a chamber. Vessels kept in 30 mg/ml BSA had L(p,e) values of 1.30 +/- 0.81 x 10(-7), cm . s-1 . cmH2O-1 (n = 9) and R(e) values of 13.8 +/- 2.6 OMEGA . cm2 (n = 3). Vessels kept in PSA had L(p,e) values of 0.257 +/- 0.125 X 10(-7) cm . s-1 . cmH2O-1 (n = 5) and R(e) values of 21 +/- 6.3 OMEGA . cm2 (n = 4). The differences between L(p,e) and R(e) in BSA and PSA were statistically significant (P < 0.05). In vessels kept in PSA, switching to BSA caused a doubling of L(p,e). Lower L(p,e) and higher R(e) in PSA as compared with those in BSA suggest that specificity for the autologous albumin is a general phenomenon in mammalian endothelium and that albumin binding to specific sites is associated with its permeability effect. C1 NIDDKD,CELL BIOL & GENET LAB,BLDG 8,RM 403,BETHESDA,MD 20892. UNIV PUERTO RICO,DEPT CHEM ENGN,MAYAGUEZ,PR 00709. UNIV PUERTO RICO,DEPT PHYSIOL,SAN JUAN,PR 00936. US FDA,DIV CARDIORENAL DRUG PROD,BETHESDA,MD 20892. NR 35 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1993 VL 264 IS 5 BP H1382 EP H1387 PN 2 PG 6 WC Physiology SC Physiology GA LD347 UT WOS:A1993LD34700007 ER PT J AU ZARKIN, GA DEAN, N MAUSKOPF, JA WILLIAMS, R AF ZARKIN, GA DEAN, N MAUSKOPF, JA WILLIAMS, R TI POTENTIAL HEALTH BENEFITS OF NUTRITION LABEL CHANGES SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SERUM-CHOLESTEROL; CANCER; MORTALITY; COLON; DISEASE; DIET; RISK; FAT; BREAST; RECTUM AB Objectives. The Nutrition Labeling and Education Act of 1990 mandates the Food and Drug Administration to promulgate changes in nutrition labeling regulations. This study investigates the potential health benefits associated with expected changes in food consumption resulting from the act. Methods. This paper provides four estimates of the potential health benefits from the dietary changes expected to occur as result of the 1990 act. The upper bound estimates begin with the premise that all consumers will adopt the daily reference values of total fat, saturated fat, and cholesterol. The lower bound estimate is based on consumers' responses to a shelf-labeling program sponsored by the Food and Drug Administration in the 1980s. A computer model developed by Dr. Warren Browner and his associates was used to estimate the health benefits from reduced nutrient intakes. Results. Estimates of the number of discounted life-years gained nationwide for the first 20 years after the implementation of the act range from a high of 1.2 million to a low of 40 000. Conclusions. The results of the study highlight that relatively small changes in nutrient intakes may generate large public health benefits. C1 BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. US FDA,WASHINGTON,DC 20204. RP ZARKIN, GA (reprint author), RES TRIANGLE INST,CTR ECON RES,POB 12194,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 37 Z9 38 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 1993 VL 83 IS 5 BP 717 EP 724 DI 10.2105/AJPH.83.5.717 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LB825 UT WOS:A1993LB82500021 PM 8484455 ER PT J AU WYSOWSKI, DK BAUM, C AF WYSOWSKI, DK BAUM, C TI THE VALIDITY OF MEDICAID DIAGNOSES OF HIP FRACTURE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter RP WYSOWSKI, DK (reprint author), US FDA,DIV EPIDEMIOL & SURVEILLANCE,HFD-733,ROCKVILLE,MD 20857, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 1993 VL 83 IS 5 BP 770 EP 770 DI 10.2105/AJPH.83.5.770 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LB825 UT WOS:A1993LB82500037 PM 8484469 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI TAMOXIFEN FOR CARCINOMA OF THE MALE BREAST - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP NIGHTINGALE, SL (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 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 MAY 1 PY 1993 VL 118 IS 9 BP 749 EP 749 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KY502 UT WOS:A1993KY50200025 ER PT J AU OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW AF OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW TI PREDOMINANT T-CELL RECEPTOR (TCR) V-ALPHA, V-BETA, AND J-BETA GENE USAGE IN MUSCLE OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES (IIM) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R18 EP R18 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900072 ER PT J AU CHAE, YH YUN, CH GUENGERICH, FP KADLUBAR, FF ELBAYOUMY, K AF CHAE, YH YUN, CH GUENGERICH, FP KADLUBAR, FF ELBAYOUMY, K TI ROLES OF HUMAN HEPATIC AND PULMONARY CYTOCHROME-P450 ENZYMES IN THE METABOLISM OF THE ENVIRONMENTAL CARCINOGEN 6-NITROCHYRSENE SO CANCER RESEARCH LA English DT Article ID HUMAN-LIVER-MICROSOMES; POLYCYCLIC AROMATIC-HYDROCARBONS; DNA ADDUCT FORMATION; OXIDATIVE DRUG-METABOLISM; ISOLATED RAT HEPATOCYTES; NEWBORN MOUSE ASSAY; SACCHAROMYCES-CEREVISIAE; SALMONELLA-TYPHIMURIUM; GENETIC-POLYMORPHISM; REDUCTIVE METABOLISM AB 6-Nitrochrysene is remarkably tumorigenic in the lung and liver of newborn mice and approximates the activities of certain ultimate carcinogenic metabolites of polycyclic aromatic hydrocarbons. Previous studies have indicated that the major metabolic activation pathway of 6-nitrochrysene in newborn mice is initially through the formation of the proximate tumorigen trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene with subsequent formation of trans-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-aminochrysene. In order to provide information on the possible risk associated with human exposure to 6-nitrochrysene, the ability of human hepatic and pulmonary microsomes to metabolize 6-nitrochrysene was investigated. The major metabolites identified in 11 hepatic microsomes were trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene, trans-9,10-dihydro-9,10-dihydroxy-6-nitrochrysene, trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene, 6-aminochrysene, and chrysene-5,6-quinone. Following the incubations of 6-nitrochrysene with 11 different human pulmonary microsomes, qualitatively similar metabolic patterns were obtained, although quantitative differences were evident. These results demonstrated that human liver and lung are capable of metabolizing 6-nitrochrysene to known potent carcinogenic metabolites via ring oxidation and nitroreduction. In an attempt to define the roles of individual human hepatic P450 involved in the metabolism of 6-nitrochrysene, the catalytic activities known to be associated with a specific P450 were analyzed and compared with the levels of each metabolite of 6-nitrochrysene formed with the same microsomes. Rates of phenacetin O-deethylation (P450 1A2) and nifedipine oxidation (P450 3A4) were well correlated with the rates of formation of trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene and 6-aminochrysene, respectively. Inhibition studies with specific P450 inhibitors and antibodies further support the view that P450 1A2 and P450 3A4 are the major forms responsible for the formation of trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene and 6-aminochrysene, respectively, in human liver. Further metabolism of trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene appears to require P450 3A4. In the human lung, P450 1A1 appears to play a major role in the metabolism of 6-nitrochrysene to trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene. These results provide some requisite knowledge for evaluating human susceptibility to 6-nitrochrysene. C1 AMER HLTH FDN,DIV CHEM CARCINOGENESIS,VALHALLA,NY 10595. VANDERBILT UNIV,MED CTR,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. NATL CTR TOXICOL RES,OFF RES,JEFFERSON,AR 72079. FU NCI NIH HHS [CA 44353, CA 35519]; NIEHS NIH HHS [ES 00267] NR 47 TC 41 Z9 43 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1993 VL 53 IS 9 BP 2028 EP 2034 PG 7 WC Oncology SC Oncology GA LA561 UT WOS:A1993LA56100013 PM 8481905 ER PT J AU RINEHART, CA LAUNDON, CH MAYBEN, JP LYNCOOK, BD KAUFMAN, DG AF RINEHART, CA LAUNDON, CH MAYBEN, JP LYNCOOK, BD KAUFMAN, DG TI CONDITIONAL IMMORTALIZATION OF HUMAN ENDOMETRIAL STROMAL CELLS WITH A TEMPERATURE-SENSITIVE SIMIAN VIRUS-40 SO CARCINOGENESIS LA English DT Article ID HUMAN-DIPLOID FIBROBLASTS; SENESCENT HUMAN-FIBROBLASTS; MALIGNANT TRANSFORMATION; NEOPLASTIC TRANSFORMATION; CELLULAR SENESCENCE; GENE AMPLIFICATION; LIFE-SPAN; S-PHASE; KERATINOCYTES; ANTIGEN AB The study of immortalization and other alterations associated with neoplastic transformation of endometrial stromal cells is important to understanding the development of uterine sarcomas and mixed tumors. Because stromal cells are important regulators of associated epithelial cells, alterations in the regulation of stromal cell proliferation that influence epithelial cells may also contribute to the development of endometrial carcinomas. To study immortalization and associated phenotypic and genetic alterations of human endometrial stromal cells, cultures were transfected with a plasmid containing an ori-, temperature-sensitive mutant SV40, A209 (tsSV40). Morphologically transformed colonies were selected and propagated at the permissive temperature until they entered 'crisis'. In contrast to human fibroblasts, every clone tested was immortalization competent. The frequency of immortalization was approximately 1 X 10(-6). One uncloned and six cloned cell lines escaped from crisis and appear to be immortal. Two clones, M4 and B10T1, were selected for further study. Immortalization is conditional; proliferative arrest occurs at the restrictive temperature for large T antigen function. Furthermore, withdrawal of the large T antigen results in expression of the senescent phenotype of enlarged, flattened cells. Colony-forming efficiency at the restrictive temperature was undetectable. Immortalization is also associated with several genetic alterations. The DNA content of tsSV40 transfected cells was either diploid or tetraploid in the precrisis stage of proliferation, but became aneuploid upon immortalization. Several structural rearrangements of chromosomes were detected in the immortalized stromal cells which differ from those found in SV40 immortalized fibroblasts. Although their capacity for anchorage-independent proliferation (AIP) is variable, tsSV40-immortalized endometrial stromal cells have a higher capacity for AIP than their tsSV40-transfected progenitor cells in the period of proliferation prior to 'crisis'. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. GENECARE,CHAPEL HILL,NC 27514. RP RINEHART, CA (reprint author), UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,DEPT PATHOL,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [CA 31733]; NHLBI NIH HHS [HL41983]; NICHD NIH HHS [HD21546] NR 58 TC 20 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1993 VL 14 IS 5 BP 993 EP 999 DI 10.1093/carcin/14.5.993 PG 7 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800034 PM 8389257 ER PT J AU HERRENOSAENZ, D EVANS, FE ABIAN, J FU, PP AF HERRENOSAENZ, D EVANS, FE ABIAN, J FU, PP TI FORMATION OF THE ADDUCT 6-(DEOXYGUANOSIN-N-2-YL)-3-AMINO-BENZO[A]PYRENE FROM THE MUTAGENIC ENVIRONMENTAL CONTAMINANT 3-NITROBENZO[A]PYRENE SO CARCINOGENESIS LA English DT Note ID POLYCYCLIC AROMATIC-HYDROCARBONS; DNA; METABOLISM AB 3-Nitrobenzo[a]pyrene (3-nitro-B[a]P) is a potent bacterial mutagen as a result of nitroreduction. Reaction of N-hydroxy-3-amino-B[a]P, prepared in situ from reduction of 3-nitro-B[a]P with calf thymus DNA, was studied. After enzymatic digestion of the DNA, the resulting modified nucleosides were analyzed by thermospray HPLC - MS and high-resolution proton NMR spectroscopy. The major adduct was identified as 6-(deoxyguanosin-N2-yl)-3-amino-B[a]P. The same adduct was obtained from incubation of DNA with 3-nitro-B[a]P in the presence of the mammalian nitroreductase xanthine oxidase, and hypoxanthine. These data indicate that a mammalian nitroreductase can metabolize 3-nitro-B[a]P to an activated derivative that reacts with DNA to give a novel adduct distant from the site of N-hydroxylation. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RI Abian, Joaquin/M-1965-2014 OI Abian, Joaquin/0000-0003-2823-5429 NR 16 TC 23 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1993 VL 14 IS 5 BP 1065 EP 1067 DI 10.1093/carcin/14.5.1065 PG 3 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800046 PM 8166885 ER PT J AU VANDERVEEN, JE AF VANDERVEEN, JE TI GRAIN QUALITY SO CEREAL FOODS WORLD LA English DT Editorial Material RP VANDERVEEN, JE (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF PLANT & DAIRY FOODS & BEVERAGES,WASHINGTON,DC 20204, 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 MAY PY 1993 VL 38 IS 5 BP 370 EP 370 PG 1 WC Food Science & Technology SC Food Science & Technology GA LD484 UT WOS:A1993LD48400008 ER PT J AU HORWITZ, W AF HORWITZ, W TI NOMENCLATURE FOR INTERLABORATORY ANALYTICAL STUDIES (RECOMMENDATIONS 1992) SO CHEMICKE LISTY LA English DT Note RP HORWITZ, W (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,HFF-7,WASHINGTON,DC 20204, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHEMICKE LISTY PI PRAGUE 6 PA PELLEOVA 24, PRAGUE 6, CZECH REPUBLIC 160 00 SN 0009-2770 J9 CHEM LISTY JI Chem. Listy PD MAY PY 1993 VL 87 IS 5 BP 372 EP 372 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA LF722 UT WOS:A1993LF72200011 ER PT J AU MOJCIK, CF GOURLEY, MF KLINMAN, DM KRIEG, AM GMELIGMEYLING, F STEINBERG, AD AF MOJCIK, CF GOURLEY, MF KLINMAN, DM KRIEG, AM GMELIGMEYLING, F STEINBERG, AD TI ADMINISTRATION OF A PHOSPHOROTHIOATE OLIGONUCLEOTIDE ANTISENSE TO MURINE ENDOGENOUS RETROVIRAL MCF ENV CAUSES IMMUNE EFFECTS INVIVO IN A SEQUENCE-SPECIFIC MANNER SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; FELINE LEUKEMIA-VIRUS; GENE-EXPRESSION; T-CELLS; OLIGODEOXYNUCLEOTIDES; ANALOGS; OLIGODEOXYRIBONUCLEOTIDES; REPLICATION; INHIBITION; PROTEIN C1 US FDA,CBER,DIV VIROL,BETHESDA,MD 20892. MITRE CORP,MCLEAN,VA 22102. RP MOJCIK, CF (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 37 TC 29 Z9 30 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 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD MAY PY 1993 VL 67 IS 2 BP 130 EP 136 DI 10.1006/clin.1993.1055 PG 7 WC Immunology; Pathology SC Immunology; Pathology GA KY917 UT WOS:A1993KY91700006 PM 7686091 ER PT J AU FORTESDIAS, CL MINETTI, CASA LIN, Y LIU, TY AF FORTESDIAS, CL MINETTI, CASA LIN, Y LIU, TY TI AGGLUTINATION ACTIVITY OF LIMULUS-POLYPHEMUS COAGULOGEN FOLLOWING LIMITED PROTEOLYSIS SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; JAPANESE HORSESHOE-CRAB; AMEBOCYTE LYSATE; TACHYPLEUS-TRIDENTATUS; BINDING PROTEIN; PURIFICATION; FIBRINOGEN; ALPHA-2-MACROGLOBULIN; HEMOLYMPH AB 1. A 14 kDa protein with cell agglutination properties has been purified from endotoxin-activated L. polyphemus amebocyte lysate. Amino terminal sequence analysis indicates that this protein corresponds to a proteolytically cleaved product (coagulin) of coagulogen. 2. Similar cell agglutination activity can be generated, in vitro, by proteolytic cleavage of the coagulogen with either trypsin, endogenous protease or an alpha2M/enzyme complex isolated from amebocytes. 3. Studies with [I-125]-labeled coagulogen showed that only coagulin, not the intact coagulogen, binds to rabbit erythrocytes and formalin-fixed amebocytes. 4. The cell agglutination activity of coagulin towards erythrocytes was not inhibited by various sugars tested, and was not Ca2+-dependent. 5. These findings suggest that coagulogen and coagulin are reminiscent of their mammalian counterparts, fibrinogen and fibrin, in their clotting and relative adhesive properties. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20892. RI Fortes-Dias, Consuelo/I-4896-2012; Minetti, Conceicao/B-5077-2009 OI Fortes-Dias, Consuelo/0000-0002-4494-5108; Minetti, Conceicao/0000-0002-9682-2898 NR 28 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 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD MAY PY 1993 VL 105 IS 1 BP 79 EP 85 DI 10.1016/0305-0491(93)90171-Z PG 7 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA LB946 UT WOS:A1993LB94600010 PM 7684962 ER PT J AU CARRINGTON, CD SHEEHAN, DM BOLGER, PM AF CARRINGTON, CD SHEEHAN, DM BOLGER, PM TI HAZARD ASSESSMENT OF LEAD SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE LEAD; TOLERABLE INTAKE AB Exposure to lead (Pb) continues to be a source of concern for the US Food and Drug Administration and other United States federal regulatory agencies. Blood lead levels as low as 10 mug/dl have been associated with impaired neurobehavioural and cognitive development and electrophysiological deficits in children and reduced gestational age and birth weight in infants. Blood lead levels of 10 mug Pb/dl are also of concern in pregnant women because of exposure to the fetus. Blood lead levels of 30 mug Pb/dl have been associated with elevated blood pressure and other adverse effects in adults. Thus, the values of 10 and 30 mug Pb/dl represent lowest-observed-effects levels for developing and adult populations, respectively. The ingestion levels that result in these blood levels of concern were estimated to be 60 mug Pb/day for children ages 6 years or younger, 150 mug Pb/day for children aged 7 years or older, 250 mug Pb/day for pregnant women and 750 mug Pb/day for adults. Provisional total tolerable intake levels for lead were derived from these blood lead levels for each group by applying the Renwick approach to obtain a tolerable exposure level. RP CARRINGTON, CD (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL REVIEW & EVALUATION,WASHINGTON,DC 20204, USA. NR 0 TC 20 Z9 26 U1 2 U2 3 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD MAY-JUN PY 1993 VL 10 IS 3 BP 325 EP 335 PG 11 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA LL766 UT WOS:A1993LL76600005 PM 8359314 ER PT J AU HSU, HH DONETS, M GREENBERG, HB FEINSTONE, SM AF HSU, HH DONETS, M GREENBERG, HB FEINSTONE, SM TI CHARACTERIZATION OF HEPATITIS-C VIRUS STRUCTURAL PROTEINS WITH A RECOMBINANT BACULOVIRUS EXPRESSION SYSTEM SO HEPATOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; CAPSID PROTEIN; HUMAN CARRIERS; CORE PROTEIN; INFECTION; GENOME; SERODIAGNOSIS; ORGANIZATION; ENCEPHALITIS; ANTIBODIES AB We cloned and expressed the sequences encoding the structural proteins of the hepatitis C virus in a baculovirus eukaryotic expression system. Four recombinant constructs expressed sufficient hepatitis C virus-specific proteins in insect cell culture to allow analysis of protein cleavage, glycosylation and immunoreactivity. Using immunoblot analysis, we detected a 22-kD protein corresponding to the hepatitis C virus capsid protein cleaved from a larger precursor. Recombinant constructs encoding the presumptive envelope (E1) protein produced products ranging from 30 to 35 kD, whereas constructs encoding the presumptive E2/NS1 protein expressed products ranging in size from 68 to 73 kD. The recombinant envelope proteins were glycosylated, as shown by sensitivity to endoglycosidase F digestion, whereas the capsid was not. We examined the immunoreactivity of these recombinant proteins using sera from 50 patients chronically infected with HCV. Forty-seven of 50 of these sera contained antibodies against the capsid, 14 (28%) also had antibodies against E1 and at least 5 (10%) had antibody against E2/NS1. Forty-seven of 50 sera (94%) were viremic, as determined on hepatitis C virus polymerase chain reaction. The three sera that were hepatitis C virus polymerase chain reaction negative did not have envelope antibodies, whereas all sera that had envelope antibodies were also hepatitis C virus polymerase chain reaction positive. Thus antibodies to baculovirus-expressed hepatitis C virus structural proteins, including E1 and E2/NS1, are found in the presence of viremia. C1 STANFORD UNIV,MED CTR,DEPT MED,STANFORD,CA 94305. US FDA,DIV VIROL,BETHESDA,MD 20892. RP HSU, HH (reprint author), VET AFFAIRS PALO ALTO MED CTR,DEPT MED,154-C,3801 MIRANDA AVE,PALO ALTO,CA 94304, USA. NR 31 TC 49 Z9 53 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1993 VL 17 IS 5 BP 763 EP 771 DI 10.1016/0270-9139(93)90149-H PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LC825 UT WOS:A1993LC82500002 PM 8387945 ER PT J AU BRANHAM, WS LYNCOOK, BD ANDREWS, A SHEEHAN, DM AF BRANHAM, WS LYNCOOK, BD ANDREWS, A SHEEHAN, DM TI GROWTH OF SEPARATED AND RECOMBINED NEONATAL RAT UTERINE LUMINAL EPITHELIUM AND STROMA ON EXTRACELLULAR-MATRIX - EFFECTS OF INVIVO TAMOXIFEN EXPOSURE SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE UTERUS; EPITHELIUM; STROMA; EXTRACELLULAR MATRIX; DIFFERENTIATION; ANTIESTROGEN ID RECONSTITUTED BASEMENT-MEMBRANE; COLLAGEN GEL CULTURE; FUNCTIONAL-DIFFERENTIATION; CELLS; ESTROGEN; GLAND; DIETHYLSTILBESTROL; PROLIFERATION; COMPONENTS; EXPRESSION AB We have developed a system for serum-free culture of separated uterine epithelium and stroma from 11-day-old rats recombined on extracellular matrix extracted from Englebreth-Holm-Swarm tumors. Epithelium grew and, after 2 days in culture, developed into luminal epithelial spheres (LES) surrounding a fluid-filled lumen. Individual LES cells maintained epithelial cell characteristics such as basally located nuclei, apical microvilli (oriented toward the lumen), lateral membranes with interdigitations and desmosomes, secretory Golgi complexes, and abundant mitochondria and rough endoplasmic reticulum. Secretory vesicles were ubiquitous throughout the luminal fluid. Addition of 17beta-estradiol to the growth medium increased the number and longevity of the LES. Prior exposure of uteri to tamoxifen via s.c. injection in vivo on postnatal Days 1 to 5 reduced or completely inhibited formation of LES in vitro. These effects occurred regardless of whether the stromal or epithelial component of the recombinant tissue was exposed to tamoxifen. These data suggest a directive property of neonatal stroma in culture resulting in the formation of highly secretory spherical epithelial structures completely enclosing a lumen. LES formation is responsive to both estrogen (positive response) and antiestrogen (negative response). C1 US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. US FDA,NATL CTR TOXICOL RES DEPT HLTH & HUMAN SERV,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM,LITTLE ROCK,AR 72201. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL,LITTLE ROCK,AR 72201. RP BRANHAM, WS (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT HLTH & HUMAN SERV,JEFFERSON,AR 72079, USA. NR 32 TC 4 Z9 4 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI UPPER MARLBORO PA 9315 LARGO DR W #255, UPPER MARLBORO, MD 20774-4755 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD MAY PY 1993 VL 29A IS 5 BP 408 EP 414 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA LJ342 UT WOS:A1993LJ34200014 PM 8314735 ER PT J AU BETTS, M BEINING, P BRUNSWICK, M INMAN, J ANGUS, RD HOFFMAN, T GOLDING, B AF BETTS, M BEINING, P BRUNSWICK, M INMAN, J ANGUS, RD HOFFMAN, T GOLDING, B TI LIPOPOLYSACCHARIDE FROM BRUCELLA-ABORTUS BEHAVES AS A T-CELL-INDEPENDENT TYPE-1 CARRIER IN MURINE ANTIGEN-SPECIFIC ANTIBODY-RESPONSES SO INFECTION AND IMMUNITY LA English DT Article ID GAMMA-INTERFERON; NORMAL MICE; COVALENT; PROTEINS; INVITRO; IMMUNODEFICIENCY; LYMPHOCYTES; EXPRESSION; INDUCTION; SURFACES AB In order to determine the carrier nature of lipopolysaccharide from Brucella abortus (LPS-BA) in evoking humoral responses, normal and immunodeficient mice were immunized with trinitrophenyl (TNP)-conjugated LPS-BA (TNP-LPS-BA) and the responses were compared with those to known T-dependent and T-independent antigens. TNP-LPS-BA, like T-independent type 1 (TI-1) antigens such as TNP-BA and TNP-LPS from Escherichia coli (TNP-LPS-EC), generated anti-TNP responses in BALB/c, athymic BALB/c nu/nu, and CBA/N mice. In contrast, N-2,4-dinitrophenyl-beta-alanylglycylglycyl-substituted keyhole limpet hemocyanin, a typical T-dependent antigen, was not immunogenic in athymic mice, and TNP-Ficoll (T-independent type 2) was ineffective in eliciting humoral responses in CBA/N mice. These results indicate that LPS from B. abortus acts as a TI-1 carrier in generating antibody responses. In C3H/HeJ mice, TNP-LPS-BA generated higher-titer immunoglobulin G1 (IgG1), IgG2a, and IgG2b anti-TNP antibodies than TNP-LPS-EC. Compared with those from BALB/c mice, pure resting B cells isolated from C3H/Hej mice exhibited a 30-fold lower proliferative response to LPS-EC, whereas the LPS-BA response was reduced to a lesser extent (5-fold). This suggests that the disparity observed in antibody titers was due to different abilities of LPS from B. abortus and E. coli to stimulate C3H/HeJ B cells. The ability of LPS from B. abortus to act as a carrier in generating humoral immune responses indicates that LPS-BA can be substituted for whole B. abortus organisms in vaccine development. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,CELL BIOL LAB,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. USDA,NATL VET SERV LABS,SCI & TECHNOL ANIM & PLANT HLTH INSPECT SERV,AMES,IA 50010. NR 33 TC 22 Z9 22 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 1993 VL 61 IS 5 BP 1722 EP 1729 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KZ177 UT WOS:A1993KZ17700017 PM 8478060 ER PT J AU GU, XX TSAI, CM AF GU, XX TSAI, CM TI PREPARATION, CHARACTERIZATION, AND IMMUNOGENICITY OF MENINGOCOCCAL LIPOOLIGOSACCHARIDE-DERIVED OLIGOSACCHARIDE-PROTEIN CONJUGATES SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; A NEISSERIA-MENINGITIDIS; O-POLYSACCHARIDE TOXIN; OUTER-MEMBRANE PROTEIN; VACCINES; LIPOPOLYSACCHARIDE; DISEASE; ANTIBODIES; SEROTYPES; ANTIGENS AB A method was developed for coupling carboxylic acid-containing oligosaccharides (OS) to proteins. An OS was isolated from Neisseria meningitidis group A strain Al lipooligosaccharide (LOS). This LOS has no human glycolipid-like lacto-N-neotetraose structure and contains multiple immunotypes, including L8, found in group B and C strains. The carboxylic acid at 2-keto-3-deoxyoctulosonic acid of the OS was linked through adipic acid dihydrazide to tetanus toxoid. The molar ratio of the OS to tetanus toxoid in three conjugates ranged from 11:1 to 19:1. The antigenicity of the OS was conserved in these conjugates, as measured by an enzyme-linked immunosorbent assay (ELISA) and an inhibition ELISA with polyclonal and monoclonal antibodies to A1 LOS. These conjugates induced immunoglobulin G antibodies to A1 LOS in mice and rabbits. The immunogenicity of the conjugates in rabbits was enhanced by use of monophosphoryl lipid A plus trehalose dimycolate as an adjuvant. The resulting rabbit antisera cross-reacted with most of 12 prototype LOSs and with LOSs from two group B disease strains, 44/76 and BB431, in an ELISA and in Western blotting (immunoblotting), which revealed a 3.6-kDa reactive band in these LOSs. The rabbit antisera showed bactericidal activity against homologous strain A1 and heterologous strains 44/76 and BB431. These results indicate that conjugates derived from A1 LOS can induce antibodies against many LOS immunotypes from different organism serogroups, including group B. OS-protein conjugates derived from meningococcal LOSs may therefore be candidate vaccines to prevent meningitis caused by meningococci. C1 US FDA,CTR BIOL EVALUAT & RES,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 63 TC 32 Z9 34 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 1993 VL 61 IS 5 BP 1873 EP 1880 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KZ177 UT WOS:A1993KZ17700038 PM 8478076 ER PT J AU SETH, A MARIANO, J METCALF, R LI, H PANAYIOTAKIS, A PANOTOPOULOU, E PAPAEVANGELOU, ME KOTTARIDIS, SD PAPAS, TS AF SETH, A MARIANO, J METCALF, R LI, H PANAYIOTAKIS, A PANOTOPOULOU, E PAPAEVANGELOU, ME KOTTARIDIS, SD PAPAS, TS TI RELATIVE PAUCITY OF P53 GENE-MUTATIONS IN MALE BREAST CARCINOMAS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE P53 GENE MUTATIONS; PCR AMPLIFICATION; SSCP ANALYSIS ID TUMOR SUPPRESSOR; CANCER; NEOPLASMS AB Mutations of the p53 suppressor -ene are the most common genetic lesion noted in human cancers and appear to be relatively common (30%) as somatic cell mutations in female breast cancer. p53 mutations have also been frequently reported in familial breast cancers as in Li-Fraumeni syndrome (LFS). Males with breast cancer are far rarer than females. We investigated the mutational spectra of the p53 gene in male breast cancers. Of 10 samples analyzed for p53 mutations in exons 5, 6. 7 and 8, only two showed point mutations corresponding to amino acid residues 248 and 290. One of the point mutations turned out to be a silent change, thus representing only DNA polymorphism. Although the number of male breast cancer samples thus far examined is small, the p53 mutations in male breast cancer (10%), unlike females (30%), does not appear to be as frequent. C1 US FDA,CBER,MOLEC MED GENET LAB,BETHESDA,MD 20892. DYN CORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. PAPANIKOLAOU RES CTR ONCOL & EXPTL SURG,HELLEN ANTICANC INST,ATHENS,GREECE. RP SETH, A (reprint author), NCI,MOLEC ONCOL LAB,POB B,FREDERICK,MD 21702, USA. NR 25 TC 5 Z9 5 U1 0 U2 2 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1993 VL 2 IS 5 BP 739 EP 744 PG 6 WC Oncology SC Oncology GA KY165 UT WOS:A1993KY16500004 PM 21573618 ER PT J AU MOREHOUSE, KM KIESEL, M KU, Y AF MOREHOUSE, KM KIESEL, M KU, Y TI IDENTIFICATION OF MEAT TREATED WITH IONIZING-RADIATION BY CAPILLARY GAS-CHROMATOGRAPHIC DETERMINATION OF RADIOLYTICALLY PRODUCED HYDROCARBONS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article ID ELECTRON-SPIN-RESONANCE; IRRADIATED FOOD; RADIOLYSIS PRODUCTS AB When triglycerides or fatty acids are irradiated, some of the major stable products are hydrocarbons formed from the loss of CO2 and CH3COOH in various free-radical reactions. A capillary gas chromatographic procedure has been developed to monitor the presence of these radiolytically generated hydrocarbons in meats treated with ionizing radiation. Several lipid extraction procedures for isolating the radiolytically generated hydrocarbons from the irradiated meat were compared. The radiolytically generated hydrocarbons were separated from the extracted lipids on a Florisil column and determined by capillary gas chromatography. The yield of these radiolytically generated hydrocarbons was linear with absorbed dose. Data indicating the utility of this methodology to identify meat products (poultry, beef, and pork) treated with ionizing radiation are presented. RP MOREHOUSE, KM (reprint author), US FDA,DIV FOOD CHEM & TECHNOL,WASHINGTON,DC 20204, USA. NR 25 TC 21 Z9 23 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY PY 1993 VL 41 IS 5 BP 758 EP 763 DI 10.1021/jf00029a015 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA LC605 UT WOS:A1993LC60500015 ER PT J AU HOLCOMB, M THOMPSON, HC HANKINS, LJ AF HOLCOMB, M THOMPSON, HC HANKINS, LJ TI ANALYSIS OF FUMONISIN B1 IN RODENT FEED BY GRADIENT ELUTION HPLC USING PRECOLUMN DERIVATIZATION WITH FMOC AND FLUORESCENCE DETECTION SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; AMINO-ACID-ANALYSIS; FUSARIUM-MONILIFORME; CANCER; CORN AB A new, sensitive, and stable method has been developed for the analysis of fumonisin B1 in rodent feed. Fumonisin B1, which is the major fumonisin metabolite produced by the fungus Fusarium moniliforme, has been implicated in human and animal diseases. Fumonisin B1 was extracted from spiked rodent feed with acetonitrile/water (50/50) and then cleaned up with tandem C18 Sep-Pak Vac and strong anion-exchange (SAX) columns. Fumonisin B1 was eluted off the SAX column with 1% acetic acid in methanol and quantitated via gradient elution HPLC using precolumn derivatization with FMOC and fluorescence detection. The minimum detectable amount in the rodent feed was 0.2 ppm. Recovery values in spiked rodent feed averaged 83% over the range 2-20 ppm. RP HOLCOMB, M (reprint author), US FDA, US PHS, NATL CTR TOXICOL RES, OFF RES, DIV CHEM, JEFFERSON, AR 72079 USA. NR 17 TC 60 Z9 62 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY PY 1993 VL 41 IS 5 BP 764 EP 767 DI 10.1021/jf00029a016 PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA LC605 UT WOS:A1993LC60500016 ER PT J AU HORWITZ, W ALBERT, R NESHEIM, S AF HORWITZ, W ALBERT, R NESHEIM, S TI RELIABILITY OF MYCOTOXIN ASSAYS - AN UPDATE SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE-CHARACTERISTICS; VARIABILITY; FOODS AB The precision parameters of the method-performance (collaborative) studies for mycotoxins published in the literature through 1991 have been recalculated on a uniform basis by following the International Union of Pure and Applied Chemistry protocol. About 80% of the 793 accepted assays for mycotoxins, almost all of which have been conducted by thin-layer chromatography (TLC), liquid chromatography (LC), and enzyme-linked immunosorbent assays (ELISA), exhibit relative standard deviations among laboratories (RSD(R)) that are less than 2 times the values predicted from the Horwitz equation: RSD(R), % = 2(1-0.5log10C) where C is the concentration expressed as a decimal fraction. The precision of TLC and LC methods is about the same, but that of ELISA is somewhat poorer. For those commodities for which sufficient data exist to provide a meaningful comparison, the methods applied to cottonseed products have the best precision and com the worst, with peanuts intermediate. Overall, however, the primary factor affecting RSD(R) is concentration, more or less independent of analyte, method, matrix, and age of the study. If it is assumed that the test results are normally distributed and that an RSD(R) of 50% is the point where effective control of the results begins to be lost (a value equivalent to the production of 2% false-negative values), then relying on the Horwitz curve, the limit of quantitative measurement is the single digit, i.e., 5, mug/kg (10(-9); ppb) concentration for solid food commodities. Such a value must be considered as a limit applicable to a single analyte, aflatoxin B1, and not as a mean, and not applicable to the sum of the individual components, each of whose associated standard deviation would lie in the unacceptable region. Enforcement of a 5 mug aflatoxin B1/kg limit, under the assumptions made, requires that a responsible manufacturer and a prudent regulator operate at opposite extremes of tolerance limits: e.g., the producer at 2 mug/kg and the consumer at 10. A proposed Codex ''maximum level'' of 0.05 mug aflatoxin M1/kg milk cannot be supported by the available data applied in an interlaboratory enforcement environment. These conclusions are also supported by an examination of the reported data from the ongoing, large-scale proficiency studies routinely performed by the American Oil Chemists' Society and the International Agency for Research on Cancer. RP HORWITZ, W (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 30 TC 51 Z9 54 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1993 VL 76 IS 3 BP 461 EP 491 PG 31 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA LD679 UT WOS:A1993LD67900001 PM 8318839 ER PT J AU YESS, NJ GUNDERSON, EL ROY, RR AF YESS, NJ GUNDERSON, EL ROY, RR TI UNITED-STATES-FOOD-AND-DRUG-ADMINISTRATION MONITORING OF PESTICIDE-RESIDUES IN INFANT FOODS AND ADULT FOODS EATEN BY INFANTS CHILDREN SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TOTAL DIET AB The U.S. Food and Drug Administration uses 3 approaches to monitor pesticide residues in foods: regulatory monitoring, incidence/level monitoring, and the Total Diet Study. The results of monitoring infant foods and adult foods that may be eaten by infants/children under these 3 approaches are presented. Under regulatory monitoring, which is performed to enforce tolerances set by the U.S. Environmental Protection Agency (EPA), during fiscal years 1985-1991, over 10 000 such domestic and imported food samples were collected and analyzed, and under the Total Diet Study, in which pesticide residue intakes are estimated in foods prepared for consumption, the food items in 27 market baskets were analyzed. Under incidence/level monitoring, which is complementary to regulatory monitoring, over 4000 analyses were performed on infant foods and adult foods eaten by children. Fewer than 50 of the 10 000 regulatory samples had violative residues; nearly all of those were residues for which there was no tolerance for the particular commodity/pesticide combination. Under incidence/level monitoring and the Total Diet Study, the levels of pesticide residues found in infant foods and adult foods eaten by children were well below tolerances set by EPA. RP YESS, NJ (reprint author), US FDA,OFF PLANT & DAIRY FOODS & BEVERAGES,WASHINGTON,DC 20204, USA. NR 20 TC 28 Z9 28 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 MAY-JUN PY 1993 VL 76 IS 3 BP 492 EP 507 PG 16 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA LD679 UT WOS:A1993LD67900002 PM 8318840 ER PT J AU HANNA, GM LAUCAM, CA AF HANNA, GM LAUCAM, CA TI STABILITY-INDICATING PROTON NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPIC ASSAY-METHOD FOR FUROSEMIDE IN TABLETS AND INJECTIONS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID 4-CHLORO-5-SULFAMOYLANTHRANILIC ACID; LIQUID-CHROMATOGRAPHY; ABSORPTION; METABOLITE AB A simple, specific, and accurate proton nuclear magnetic resonance (H-1-NMR) spectroscopic method has been developed for the identification and assay of furosemide and its degradation product, 4-chloro-5-sulfamoylanthranilic acid (CSA), in tablets and injections. Dissolution of the sample in D2O-NaOD resulted in a solution yielding the required separation among the resonance signals of furosemide, CSA, and tert-butyl alcohol, the internal standard. The mean +/- SD recovery values of furosemide and CSA from 10 synthetic formulations were 99.6 +/- 0.8 and 98.9 +/- 1.7%, respectively. Commercial tablets (6 lots) and injections (5 lots) of furosemide were assayed by the proposed method and found to contain 53.1-99.8% furosemide and 0.3-45.2% CSA. C1 ST JOHNS UNIV,COLL PHARM & ALLIED HLTH PROFESS,JAMAICA,NY 11439. RP HANNA, GM (reprint author), US FDA,NEW YORK REG LAB,850 3RD AVE,BROOKLYN,NY 11232, USA. NR 28 TC 11 Z9 11 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 1993 VL 76 IS 3 BP 526 EP 530 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA LD679 UT WOS:A1993LD67900005 PM 8318842 ER PT J AU SNELL, RP AF SNELL, RP TI SOLID-PHASE EXTRACTION AND LIQUID-CHROMATOGRAPHIC DETERMINATION OF MONOPHTHALATES AND PHTHALIDE EXTRACTED FROM SOLUTION ADMINISTRATION SETS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID DI-(2-ETHYLHEXYL) PHTHALATE; DI(2-ETHYLHEXYL) PHTHALATE; ESTERS; HEMODIALYSIS; BAGS; ACID; RATS AB A liquid chromatographic procedure is described for the determination of phthalide, monobutyl phthalate, and mono-2-ethylhexyl phthalate leached by water from solution administration sets. Recoveries varied from 88.8% for phthalide at 1 mug/50 mL to 113% for monobutyl phthalate at 6 mug/50 mL. Relative standard deviations at 1 mug/50 mL were 2.59% for phthalide, 3.54% for monobutyl phthalate, and 11.6% for mono-2-ethylhexyl phthalate. At 6 mug/50 mL, the relative standard deviation for mono-2-ethylhexyl phthalate decreased to 3.88%. Reproducibilities for 5 standard injections were 1.40% for phthalide, 1.84% for monobutyl phthalate, and 1.95% for mono-2-ethylhexyl phthalate. Correlation coefficients were 1.00 for the 3 compounds. Five sets from 2 manufacturers were examined. No phthalide or monobutyl phthalate was found. One manufacturer's sets contained 37.6-44.4 mug/L mono-2-ethylhexyl phthalate. The sample matrix had some interference if phthalide or monobutyl phthalate was present. RP SNELL, RP (reprint author), US FDA,STERIL ANAL RES CTR,240 HENNEPIN,MINNEAPOLIS,MN 55401, USA. NR 18 TC 25 Z9 25 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 MAY-JUN PY 1993 VL 76 IS 3 BP 531 EP 534 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA LD679 UT WOS:A1993LD67900006 PM 8318843 ER PT J AU SHAIKH, B JACKSON, J AF SHAIKH, B JACKSON, J TI IMPROVED LIQUID-CHROMATOGRAPHIC DETERMINATION OF NEOMYCIN-B IN BOVINE KIDNEY SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An improved liquid chromatographic (LC) method was developed for the determination of neomycin B in bovine kidney tissue. The tissue is homogenized twice in phosphate buffer; homogenate is centrifuged, and the supernatant is deproteinated by heat. The extract is acidified and mixed with ion-pair concentrate, and neomycin B is determined by an LC system consisting of an ion-pairing mobile phase, a reversed-phase ODS column, postcolumn derivatization with o-phthalaldehyde reagent, and fluorometric detection. Average recoveries of neomycin B from kidney tissues spiked at 3, 6, and 12 ppm were 103, 99, and 104%, with 9.7, 7.9, and 3.7% intralaboratory coefficients of variation, respectively, using a standard curve prepared in buffer. The method was used to determine neomycin B in kidney tissue obtained from a calf killed 14 days after intramuscular dosing with neomycin (5 mg/lb). The tissue was found to contain about 3 ppm neomycin B. The LC conditions were also used to assay control samples of muscle, liver, milk, plasma, and urine. No interfering peaks were noted at the elution position of neomycin B. RP SHAIKH, B (reprint author), US FDA,CTR VET MED,DIV VET MED RES,VET PHARMACOL TOXICOL BRANCH,BARC EAST,BLDG 328A,BELTSVILLE,MD 20705, USA. NR 5 TC 11 Z9 13 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 1993 VL 76 IS 3 BP 543 EP 548 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA LD679 UT WOS:A1993LD67900009 PM 8318846 ER PT J AU OLSON, LD GILBERT, AA AF OLSON, LD GILBERT, AA TI CHARACTERISTICS OF MYCOPLASMA-HOMINIS ADHESION SO JOURNAL OF BACTERIOLOGY LA English DT Note ID ATTACHMENT; PNEUMONIAE; GLYCOLIPIDS; INFERTILITY; CULTURES AB Mycoplasma hominis, a human pathogen, has previously been observed to bind to sulfatide separated on thin-layer chromatograms. It has not been demonstrated, however, that the binding is not simply a nonspecific ionic interaction. The ability of a low-passage patient isolate of M. hominis to adhere to glycoconjugates other than sulfatide and the characteristics of its binding to sulfatide were studied. Mycoplasmas were found to bind strongly and specifically in a temperature- and dose-dependent manner to only sulfatide of all of the glycolipids and glycoproteins tested. The avidity and specificity of binding, as well as the ability to inhibit the interaction specifically, suggest that the receptors to which M. hominis binds, particularly in the human urogenital tract, from which it is frequently isolated, are primarily, if not solely, sulfated glycolipids. RP OLSON, LD (reprint author), US FDA,CTR BIOL EVALUAT & RES,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. NR 14 TC 18 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1993 VL 175 IS 10 BP 3224 EP 3227 PG 4 WC Microbiology SC Microbiology GA LB792 UT WOS:A1993LB79200057 PM 8491739 ER PT J AU TRAN, TT HITCHINS, AD AF TRAN, TT HITCHINS, AD TI RECOVERY LIMITS OF HEAT-INJURED LISTERIA-MONOCYTOGENES FROM ENRICHMENT BROTH AND ENRICHED CULTURES OF INOCULATED FOODS SO JOURNAL OF FOOD SAFETY LA English DT Article AB Recovery of heat-injured Listeria monocytogenes strain LM82 was evaluated quantitatively in Listeria enrichment broth (LEB) and in enriched cultures of cooked shrimp and Brie cheese. LM82 cells [10(8) colony forming units (CFU)/ml] were heated for 60 min at 52C in phosphate-buffered saline. After 24 and 48 h enrichment, injured LM82 (6 replicates at each of 5 inoculation levels) were isolated on 3 selective media: lithium chloride-phenylethanol-moxalactam agar (LPMA), modified McBride agar (MMA) and Oxford agar (OXA). The recovery limit was expressed as a 50% end point value (RL50), which is the calculated inoculation value necessary to recover LM82 on half of the replicates of each type of isolation agar plate after streaking from the enrichment of measured inoculum. The RL50 values for injured cells were comparable to those of uninjured cells after 48 h enrichment in LEB without food. The type of isolation agar did not affect the RL50 value, although with food, MMA gave consistently but not significantly higher values, i.e., recovery inferior to that of LPMA and OXA. RL50 values were higher in Brie and cooked shrimp, presumably because of the competitive microflora in those foods. Addition of lactose or pyruvate to LEB improved recovery but had little or no effect when foods were present. RP TRAN, TT (reprint author), US FDA,DIV MICROBIOL STUDIES,200 C ST SW,WASHINGTON,DC 20204, USA. NR 14 TC 2 Z9 2 U1 1 U2 1 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD MAY PY 1993 VL 13 IS 3 BP 185 EP 193 DI 10.1111/j.1745-4565.1993.tb00105.x PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA LR450 UT WOS:A1993LR45000003 ER PT J AU SCHMUED, LC SNAVELY, LF AF SCHMUED, LC SNAVELY, LF TI PHOTOCONVERSION AND ELECTRON-MICROSCOPIC LOCALIZATION OF THE FLUORESCENT AXON TRACER FLUORO-RUBY (RHODAMINE-DEXTRAN-AMINE) SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Note DE FLUORO-RUBY; TETRAMETHYLRHODAMINE DEXTRAN-AMINE; PHOTOCONVERSION; FLUORESCENT AXON TRACERS; ELECTRON MICROSCOPY; FLUOROGOLD ID ANTEROGRADE; NEURONS; GOLD AB Fluoro-Ruby, the fluorescent tetramethylrhodamine-dextranamine used to demonstrate anterograde axon transport, has been successfully photoconverted and subsequently localized by electron microscopy. The photoconversion was accomplished by irradiating the tissue with green light while bathing it in a solution containing DAB. The tissue could then be examined by brightfield microscopy or processed for conventional electron microscopy. Potential advantages of the technique include greater permanence and contrast at the light microscopic level and the ability to resolve synaptic connectivity at the electron microscopic level. C1 UNIV VIRGINIA,MED CTR,SCH MED,DEPT OTOLARYNGOL,CHARLOTTESVILLE,VA 22901. RP SCHMUED, LC (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079, USA. FU NICHD NIH HHS [HD07323] NR 13 TC 18 Z9 18 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 1993 VL 41 IS 5 BP 777 EP 782 PG 6 WC Cell Biology SC Cell Biology GA KY455 UT WOS:A1993KY45500019 PM 7682231 ER PT J AU JU, WD SCHILLER, JT KAZEMPOUR, MK LOWY, DR AF JU, WD SCHILLER, JT KAZEMPOUR, MK LOWY, DR TI TGF-ALPHA ENHANCES LOCOMOTION OF CULTURED HUMAN KERATINOCYTES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID GROWTH-FACTOR-ALPHA; PSORIATIC EPIDERMIS; CELL-SURFACE; PRECURSOR; DIFFERENTIATION; EXPRESSION; INDUCTION; MIGRATION; AUTOCRINE; RECEPTORS AB A cDNA sequence coding for the full-length human transforming growth factor alpha (TGFalpha) precursor protein was introduced into and transcribed in cultured human keratinocytes, using a high-titer, high-expression, murine amphotropic retrovirus. Keratinocytes were shown capable of post-translationally modifying the TGFalpha primary translation product, with the subsequent formation of several cell-associated and secreted forms of TGFalpha, at least five of which, including the 50 amino acid mature species, can potentially bind and activate the epidermal growth factor receptor. Cells overexpressing the TGFalpha gene assumed a spindled morphology with long, bipolar filamentous processes and displayed increased locomotion. The soluble, mature form of TGFalpha alone also could induce the observed changes in cell shape and motility when added to keratinocyte cultures exogenously. The effects were dose dependent, and up to fourfold increases in locomotion were caused by TGFalpha in the absence of bovine pituitary extract (BPE). The addition of BPE to high concentrations of TGFalpha further enhanced keratinocyte motility to eightfold over baseline, suggesting a synergistic interaction between the two factors. These experiments demonstrate that keratinocytes can synthesize several forms of TGFalpha and that TGFalpha, besides being mitogenic, may have other important regulatory functions in keratinocytes. C1 US FDA,DIV BIOMETR,ROCKVILLE,MD 20857. NCI,CELLULAR ONCOL LAB,ROCKVILLE,MD. NR 42 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1993 VL 100 IS 5 BP 628 EP 632 PG 5 WC Dermatology SC Dermatology GA LA730 UT WOS:A1993LA73000004 PM 8491985 ER PT J AU SCHWEMER, WL LYNCH, MA AF SCHWEMER, WL LYNCH, MA TI ISO-9000 - POLICY IMPLICATIONS FOR FDA TAKING THE PULSE OF INCREASING GLOBAL USE OF THE ISO SERIES OF UNIFORM QUALITY STANDARDS BY FDA REGULATED INDUSTRIES SO JOURNAL OF PARENTERAL SCIENCE AND TECHNOLOGY LA English DT Article RP SCHWEMER, WL (reprint author), US FDA,OFF POLICY,HF-23 ROOM 12A17,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 34 TC 1 Z9 1 U1 0 U2 0 PU PARENTERAL DRUG ASSOC, INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE, 620, BETHESDA, MD 20814 SN 0279-7976 J9 J PARENT SCI TECHN PD MAY-JUN PY 1993 VL 47 IS 3 BP 101 EP 118 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LX960 UT WOS:A1993LX96000002 PM 8360802 ER PT J AU GRAKOUI, A MCCOURT, DW WYCHOWSKI, C FEINSTONE, SM RICE, CM AF GRAKOUI, A MCCOURT, DW WYCHOWSKI, C FEINSTONE, SM RICE, CM TI CHARACTERIZATION OF THE HEPATITIS-C VIRUS-ENCODED SERINE PROTEINASE - DETERMINATION OF PROTEINASE-DEPENDENT POLYPROTEIN CLEAVAGE SITES SO JOURNAL OF VIROLOGY LA English DT Article ID NON-B-HEPATITIS; YELLOW-FEVER VIRUS; VIRAL DIARRHEA VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; RECOMBINANT INTERFERON-ALFA; PESTIVIRUS GENE-EXPRESSION; OPEN READING FRAME; HOG-CHOLERA VIRUS; NON-A-HEPATITIS; VACCINIA VIRUS AB Processing of the hepatitis C virus (HCV) H strain polyprotein yields at least nine distinct cleavage products: NH2-C-E1-E2-NS2-NS3-NS4A-NS4B-NS5A-NS5B-COOH. As described in this report, site-directed mutagenesis and transient expression analyses were used to study the role of a putative serine proteinase domain, located in the N-terminal one-third of the NS3 protein, in proteolytic processing of HCV polyproteins. All four cleavages which occur C terminal to the proteinase domain (3/4A, 4A/4B, 4B/5A, and 5A/5B) were abolished by substitution of alanine for either of two predicted residues (His-1083 and Ser-1165) in the proteinase catalytic triad. However, such substitutions have no observable effect on cleavages in the structural region or at the 2/3 site. Deletion analyses suggest that the structural and NS2 regions of the polyprotein are not required for the HCV NS3 proteinase activity. NS3 proteinase-dependent cleavage sites were localized by N-terminal sequence analysis of NS4A, NS4B, NS5A, and NS5B. Sequence comparison of the residues flanking these cleavage sites for all sequenced HCV strains reveals conserved residues which may play a role in determining HCV NS3 proteinase substrate specificity. These features include an acidic residue (Asp or Glu) at the P6 position, a Cys or Thr residue at the P1 position, and a Ser or Ala residue at the P1' position. C1 WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,660 S EUCLID AVE,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,ST LOUIS,MO 63110. US FDA,CTR EVALUAT & BIOLOG RES,DIV VIROL,BETHESDA,MD 20892. FU NCI NIH HHS [CA57973] NR 93 TC 511 Z9 522 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1993 VL 67 IS 5 BP 2832 EP 2843 PG 12 WC Virology SC Virology GA KX335 UT WOS:A1993KX33500049 PM 8386278 ER PT J AU LU, MH HINSON, WG TURTURRO, A SHELDON, WG HART, RW AF LU, MH HINSON, WG TURTURRO, A SHELDON, WG HART, RW TI CELL-PROLIFERATION BY CELL-CYCLE ANALYSIS IN YOUNG AND OLD DIETARY RESTRICTED MICE SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE CELL PROLIFERATION; CELL CYCLE ANALYSIS; DIETARY RESTRICTION; AGING; MOUSE ID CALORIC RESTRICTION; FOOD RESTRICTION; DNA-REPAIR; CARCINOGENESIS; RATS; LONGEVITY; RODENTS; TISSUES; CANCER AB The effect of dietary restriction (DR) on cell proliferation determined by cell cycle analysis in tissues of young and old mice was investigated. Using the percentage of S-phase cells as an index of cell proliferation, we found that DR inhibited cell proliferation in spleen and thymus in young mice. No significant changes were found in bone marrow and kidney in the ad libitum (AL) or DR mice regardless of age. In old mice, the DR effect was observed in spleen only. When age increased, a parallel decline in cell proliferation was evidenced by a reduced % of S-phase cells. DR produces a greater cell cycle effect in the young mice than in the old mice. The present data suggests that inhibition of cell proliferation by DR may be affected by type of tissue, age, length of DR, and capacity or rate of cell proliferation. RP LU, MH (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 55 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD MAY PY 1993 VL 68 IS 1-3 BP 151 EP 162 DI 10.1016/0047-6374(93)90147-J PG 12 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA LG147 UT WOS:A1993LG14700013 PM 8350655 ER PT J AU DIRKSEN, ML MATHERS, P JAMRICH, M AF DIRKSEN, ML MATHERS, P JAMRICH, M TI EXPRESSION OF A XENOPUS-DISTAL-LESS HOMEOBOX GENE INVOLVED IN FOREBRAIN AND CRANIOFACIAL DEVELOPMENT SO MECHANISMS OF DEVELOPMENT LA English DT Article DE CEMENT GLAND; DISTAL-LESS; FOREBRAIN; HOMEOBOX; NEURAL CREST; RETINA; VISCERAL ARCH; XENOPUS ID LAEVIS CEMENT GLAND; LIMB DEVELOPMENT; EMBRYONIC DIFFERENTIATION; TRANSCRIPTION FACTORS; SEGMENTATION GENES; EXPERIMENTAL MODEL; NERVOUS-SYSTEM; FLOOR PLATE; DROSOPHILA; HOMEODOMAIN AB Homeobox-containing genes are thought to perform essential functions in the process of pattern formation in vertebrates and invertebrates. They provide cells with positional information critical for normal embryonic development. Since most of the identified homeobox genes in Xenopus seem to provide positional information for the development of the trunk, we have concentrated on genes that may be specifically involved in the formation of the head region. Using a polymerase chain reaction strategy we have searched for Xenopus homeobox-containing genes that might provide positional cues for correct development of the brain. In this paper we report the identification and cloning of a novel gene that by homology appears to be a member of the Distal-less homeobox gene family. We show that its temporal expression patterns in the cement gland, neural crest derived visceral arches, retina and forebrain, while quite diverse, does suggest shared developmental features which may be required for correct craniofacial development and the regionalization of the Xenopus brain. Furthermore, expression of this gene at later stages is primarily restricted to the tadpole forebrain suggesting that the Distal-less gene product continues to play a role after the initial brain patterning is complete. C1 US FDA,CBER,DIV BIOCHEM & BIOPHYS,MOLEC PHARMACOL LAB,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 39 TC 60 Z9 60 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAY PY 1993 VL 41 IS 2-3 BP 121 EP 128 DI 10.1016/0925-4773(93)90042-V PG 8 WC Developmental Biology SC Developmental Biology GA LA067 UT WOS:A1993LA06700004 PM 8100141 ER PT J AU BOONE, JM PFEIFFER, DE STRAUSS, KJ ROSSI, RP LIN, PJP SHEPARD, JS CONWAY, BJ AF BOONE, JM PFEIFFER, DE STRAUSS, KJ ROSSI, RP LIN, PJP SHEPARD, JS CONWAY, BJ TI A SURVEY OF FLUOROSCOPIC EXPOSURE RATES - AAPM TASK GROUP NO 11 REPORT SO MEDICAL PHYSICS LA English DT Article AB Fluoroscopic procedures, in general, result in much higher exposures to patients than do most types of radiographic procedures [National Council on Radiation Protection, Report 100, p. 31 (1989)]. In spite of this, fluoroscopic exposure rates can vary widely between systems, and often for no apparent reason. The charge of AAPM Task Group No. 11 was to evaluate fluoroscopic exposure rates at the entrant surface of the x-ray image intensifier, and to disseminate this information so that medical physicists could compare their own exposure rate measurements with typical values. The measurement protocol was defined for various system configurations. Sheets of copper were used to attenuate the x-ray beam, and the input exposure rate at the image intensifier (at the input mode closest to 23-cm diameter) in the absence of a scattering medium was determined. With 2 mm of copper as x-ray beam filtration, the median fluoroscopic exposure rate at the image intensifier was found to be 16.5 nC/kg/s (64.0 muR/s), with an average kV of 77 and mA of 2.0 (n = 62). C1 UNIV PENN,DEPT RADIOL,PHILADELPHIA,PA 19104. CHILDRENS HOSP MED CTR,DEPT RADIOL,BOSTON,MA 02115. UNIV COLORADO,DEPT RADIOL,DENVER,CO 80202. NORTHWESTERN UNIV,MED CTR,DEPT RADIOL,CHICAGO,IL 60611. BAYLOR UNIV,MED CTR,DEPT RADIOL,DALLAS,TX. CTR DEVICES & RADIOL HLTH,BETHESDA,MD. RP BOONE, JM (reprint author), UNIV CALIF DAVIS,SACRAMENTO MED CTR,DEPT RADIOL,SACRAMENTO,CA 95817, USA. OI Lin, Pei-Jan/0000-0002-7126-3989 NR 5 TC 21 Z9 21 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY-JUN PY 1993 VL 20 IS 3 BP 789 EP 794 DI 10.1118/1.597033 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LK528 UT WOS:A1993LK52800029 PM 8350838 ER PT J AU MCMANAWAY, ME MARTI, GE TOSATO, G LIU, AK ALNASSER, AA KIWANUKA, J MAGRATH, IT AF MCMANAWAY, ME MARTI, GE TOSATO, G LIU, AK ALNASSER, AA KIWANUKA, J MAGRATH, IT TI HETEROTRANSPLANTATION OF HUMAN BURKITTS-LYMPHOMA CELL-LINES IN ATHYMIC NUDE-MICE - TUMOR-HOST RELATIONSHIPS SO PATHOBIOLOGY LA English DT Article DE BURKITTS LYMPHOMA; TUMORIGENICITY; C-MYC; NUDE MICE; LYMPHOMA; GROWTH FACTORS ID C-MYC; INVITRO; GROWTH; INVIVO AB We have explored the factors which influence tumorigenicity of Burkitt's lymphoma (BL) cell lines in athymic nude mice. Four cell lines, Namalwa, CA46, JD38, and ST486 revealed tumor incidence of 63.5, 69.0, 45.5 and 10.0%, respectively, in nude mice, but there was no correlation between tumor incidence and growth rate in vivo. Thus, growth rate and tumorigenicity are dependent upon different biochemical pathways. Evidence of tumor cell heterogeneity was demonstrated in the CA46 parent cell line. Five subclones derived from CA46 revealed varying degrees of tumor incidence (but very similar growth rates) that were consistently less than the parent CA46 line. Line 5, for example, produced 5.7-fold less tumors than the parent line. None of the BL cell lines or clones produced any metastatic lesions in liver, lung, brain, bone marrow or spleen in athymic nude mice. Northern blot analysis of c-myc mRNA levels in different BL cell lines revealed a possible relationship between percent tumor takes (but not growth rates) and the level of c-myc oncogene expression. However, no correlation was observed between c-myc mRNA levels and tumor incidence or growth rates among the CA46 clones. There was no correlation between the ability of the cell lines and the subclones to either secrete growth factors or to respond to growth factors secreted by Epstein-Barr virus-induced lymphoblastoid cells or lipopolysaccharide-activated monocytes, and their growth rates or percent tumor takes in mice. Comparison of tumor incidence and growth rates in irradiated and unirradiated mice showed that host factors influenced the growth of BL in nude mice. Tumor heterotransplantation after whole-body X-irradiation of the mice resulted in an increase in tumor incidence in 4 of 5 lines injected. At 2 weeks after cell inoculation, subclone 5 (CA46) had a 100% tumor take in irradiated mice, whereas in untreated mice the incidence was 0%. The appearance of large tumors at this early time point also indicated an increase in growth rate. However, the lack of an increase in tumor incidence after irradiation in one cell line (ST486) strongly suggests that the interaction of tumor cell characteristics, probably surface characteristics, with host factors is required for BL growth in nude mice. C1 US FDA,CBER,DIV CYTOKINE BIOL,BETHESDA,MD 20014. RAINBOW BABIES & CHILDRENS HOSP,CLEVELAND,OH 44106. RP MCMANAWAY, ME (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 18 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD MAY-AUG PY 1993 VL 61 IS 3-4 BP 164 EP 172 DI 10.1159/000163785 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA LZ085 UT WOS:A1993LZ08500006 PM 8216838 ER PT J AU HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G AF HALL, CB GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW YOGEV, R PETER, G BART, KJ BROOME, C JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G TI VITAMIN-A TREATMENT OF MEASLES SO PEDIATRICS LA English DT Article ID TRIAL; MORTALITY; CHILDREN C1 CTR DIS CONTROL,ATLANTA,GA 30333. US FDA,WASHINGTON,DC 20204. AMER THORAC SOC,NEW YORK,NY. NIH,BETHESDA,MD 20892. RI Steele, Russell/A-6075-2011 NR 18 TC 21 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 MAY PY 1993 VL 91 IS 5 BP 1014 EP 1015 PG 2 WC Pediatrics SC Pediatrics GA KZ792 UT WOS:A1993KZ79200032 ER PT J AU FERGUSON, SA PAULE, MG AF FERGUSON, SA PAULE, MG TI ACUTE EFFECTS OF PENTOBARBITAL IN A MONKEY OPERANT BEHAVIORAL-TEST BATTERY SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE PENTOBARBITAL; MONKEY; OPERANT BEHAVIOR; LEARNING; SHORT-TERM MEMORY; TIME PERCEPTION; MOTIVATION; COLOR AND POSITION DISCRIMINATION ID RHESUS-MONKEYS; DIAZEPAM; PERFORMANCE; MECHANISMS; BINDING; DRUGS AB The effects of acute pentobarbital treatment were assessed using a complex operant test battery containing five tasks in which correct performance is thought to depend upon processes associated with short-term memory and attention [delayed-matching-to-sample (DMTS)], color and position discrimination [conditioned position responding (CPR)], motivation [progressive ratio (PR)], time perception [temporal response differentiation (TRD)], and learning [incremental repeated acquisition (IRA)]. Adult, male rhesus monkeys were tested 15 min after IV injection of saline or pentobarbital (1, 3, 5.6, 10, or 15 mg/kg). Behavioral endpoints measured included percent task completed, response rate or latency, and response accuracy. The order of task sensitivity to disruption by PBT was TRD > IRA = DMTS = PR > CPR, in which sensitivity was defined as a significant disruption in any aspect of task performance. PBT slowed response rates at 10.0 and/or 15.0 mg/kg in all tasks. Accuracy was decreased in the TRD task at greater-than-or-equal-to 5.6 mg/kg but doses of greater-than-or-equal-to 10.0 mg/kg were required to decrease accuracy in the IRA, DMTS, and CPR tasks. Thus, behavior thought to model time perception (TRD) was more sensitive than behavior modeling learning (IRA), short-term memory and attention (DMTS), and motivation (PR). CPR was the least sensitive behavior. Because pentobarbital exerts its effects at least in part via GABA systems, the effects in the current study were compared with those of a previous study of the acute effects of diazepam. The two compounds exerted fundamentally different effects on operant test battery performance. RP FERGUSON, SA (reprint author), NATL CTR TOXICOL RES,DIV NEUROTOXICOL,HFT-132,NCTR DR,JEFFERSON,AR 72079, USA. NR 36 TC 24 Z9 24 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 1993 VL 45 IS 1 BP 107 EP 116 DI 10.1016/0091-3057(93)90093-9 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA KZ167 UT WOS:A1993KZ16700016 PM 8516351 ER PT J AU ZHANG, YH AF ZHANG, YH TI PATH-INTEGRAL FORMALISM FOR CLASSICAL BROWNIAN-MOTION IN A GENERAL ENVIRONMENT SO PHYSICAL REVIEW E LA English DT Note ID HIDDEN BRS INVARIANCE; MECHANICS; DYNAMICS AB The path-integral formalism for classical Brownian motion in a general environment is derived from the first principles of microdynamics by using the path-integral formulation of classical mechanics. The classical influence functional, which contains a nonlocal dissipation term and a colored noise term, is introduced. We show that there exists a classical fluctuation-dissipation relation. We also compare this classical influence functional theory with the well-known quantum influence-functional theory. RP ZHANG, YH (reprint author), US FDA, CTR BIOL EVALUAT & RES, BIOPHYS LAB, 8800 ROCKVILLE PIKE, BETHESDA, MD 20982 USA. NR 23 TC 6 Z9 6 U1 0 U2 3 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD MAY PY 1993 VL 47 IS 5 BP 3745 EP 3748 DI 10.1103/PhysRevE.47.3745 PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA LF067 UT WOS:A1993LF06700090 ER PT J AU PAULI, GH AF PAULI, GH TI FOOD-AND-DRUG-ADMINISTRATION RESPONDS SO PUBLIC HEALTH REPORTS LA English DT Letter RP PAULI, GH (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF PREMARKET APPROVAL,DIV PROD POLICY,WASHINGTON,DC 20204, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1993 VL 108 IS 3 BP 402 EP 402 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LF949 UT WOS:A1993LF94900020 ER PT J AU GREEN, S AF GREEN, S TI REGULATORY AGENCY CONSIDERATIONS AND REQUIREMENTS FOR VALIDATION OF TOXICITY TEST ALTERNATIVES SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT CONF ON APPLICATIONS OF ADVANCES IN TOXICOLOGY TO RISK ASSESSMENT CY MAY 19-21, 1992 CL WRIGHT PATTERSON AFB, OH SP ARMSTRONG LAB, OCCUPAT & ENVIRONM HLTH DIRECTORATE, TOXICOL DIV, USN, NAVAL MED RES INST DETACHMENT, USA, BIOMED RES & DEV LAB DE VALIDATION; INVITRO; ALTERNATIVES; TOXICITY AB When developing an alternative toxicity test, one must first determine whether the alternative assay is to be used as a screen or as a replacement for the traditional toxicity test. An assay used as a screen will require less stringent acceptance criteria, for it is designed to answer fewer and less complex questions (e.g., the assessment of only potential teratogenicity). An assay used as a replacement will be used to establish hazard or lack thereof (safety). In other words, a replacement assay must clearly establish whether or not a chemical is a teratogen. One should also have knowledge of and experience with the in vivo assay to be replaced. This knowledge should be of not only the procedural aspects of the test but also the regulatory information it provides (i.e., how the results are used for hazard determination). Thorough consideration of the regulatory information is critical for a test intended to be used as a replacement. Validation should include intralaboratory and interlaboratory reproducibility of results from a standard protocol, an assessment of the qualitative and quantitative aspects of the test responses, and the use of a sufficient number of chemicals representative of the defined category of interest. RP GREEN, S (reprint author), US FDA,DIV TOXICOL RES HFS505,CTR FOOD SAFETY & APPL NUTR,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 2 TC 25 Z9 25 U1 0 U2 2 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 MAY PY 1993 VL 68 IS 1-2 BP 119 EP 123 DI 10.1016/0378-4274(93)90124-G PG 5 WC Toxicology SC Toxicology GA LH577 UT WOS:A1993LH57700015 PM 8516758 ER PT J AU GOLDBERG, AM FRAZIER, JM BRUSICK, D DICKENS, MS FLINT, O GETTINGS, SD HILL, RN LIPNICK, RL RENSKERS, KJ BRADLAW, JA SCALA, RA VERONESI, B GREEN, S WILCOX, NL CURREN, RD AF GOLDBERG, AM FRAZIER, JM BRUSICK, D DICKENS, MS FLINT, O GETTINGS, SD HILL, RN LIPNICK, RL RENSKERS, KJ BRADLAW, JA SCALA, RA VERONESI, B GREEN, S WILCOX, NL CURREN, RD TI REPORT OF THE VALIDATION AND TECHNOLOGY-TRANSFER COMMITTEE OF THE JOHNS-HOPKINS-CENTER-FOR-ALTERNATIVES-TO-ANIMAL-TESTING - FRAMEWORK FOR VALIDATION AND IMPLEMENTATION OF INVITRO TOXICITY TESTS SO XENOBIOTICA LA English DT Article ID EYE IRRITATION TEST; REGULATORY ACCEPTANCE; TOXICOLOGY; PROJECT AB The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering the validation of new methods is essential for the effective transfer of new technological developments from the research laboratory into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks, a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects and endpoints of toxicity testing, and representing the academic, industrial and regulatory communities, is recommended. Test validation acceptance is contingent upon broad buy-in by disparate groups in the scientific community-academics, industry and government. This is best achieved by early and frequent communication among parties and agreement upon common goals. It is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction and refinement alternatives in toxicity testing. C1 HAZLETON LABS,VIENNA,VA 22182. AVON PROD INC,SUFFERN,NY 10901. BRISTOL MYERS SQUIBB CO,SYRACUSE,NY 13221. COSMET TOILETRY & FRAGRANCE ASSOC INC,WASHINGTON,DC 20036. US EPA,WASHINGTON,DC 20460. US FDA,LAUREL,MD 20708. EXXON BIOMED SCI INC,REHOBETH BEACH,DE 19971. US EPA,HLTH EFFECTS RES LAB,RES TRIANGLE PK,NC 27709. US FDA,OFF ANIM CARE & USE,CTR VET MED,ROCKVILLE,MD 20855. MICROBIOL ASSOCIATES INC,ROCKVILLE,MD 20850. RP GOLDBERG, AM (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR ALTERNAT ANIM TESTING,615 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 35 TC 11 Z9 13 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAY PY 1993 VL 23 IS 5 BP 563 EP 572 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LJ179 UT WOS:A1993LJ17900008 PM 8342302 ER PT J AU KINCAID, RL MARIETTA, CA MOOS, MC AF KINCAID, RL MARIETTA, CA MOOS, MC TI CHARACTERIZATION OF A 36 KDA PROTEIN FROM BOVINE BRAIN WITH STRUCTURAL HOMOLOGY TO THE TRYPANOSOMA-BRUCEI GLYCOSYL-PHOSPHATIDYL INOSITOL-PHOSPHOLIPASE-C SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,IMMUNOL SECT,ROCKVILLE,MD 20852. NIH,FDA,MOLEC PHARMACOL LAB,BETHESDA,MD 20814. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 1993 VL 7 IS 7 BP A1045 EP A1045 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84800037 ER PT J AU KOIZUMI, M LEE, C AF KOIZUMI, M LEE, C TI GLYCOSIDASE ACTIVITY OF AUTOLYSIN IN STREPTOCOCCUS-PNEUMONIAE SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 1993 VL 7 IS 7 BP A1235 EP A1235 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84801144 ER PT J AU PRADHAN, S AF PRADHAN, S TI EFFECT OF FLUPHENAZINE ON NEUROTRANSMITTER SYSTEMS IN RATS SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA,CDER,DIV BIOEQUIVALENCE,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 1993 VL 7 IS 7 BP A1087 EP A1087 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KY848 UT WOS:A1993KY84800280 ER PT J AU TAKASHIMA, A KENIMER, JG AF TAKASHIMA, A KENIMER, JG TI REGULATION OF MUSCARINIC STIMULATION OF NOREPINEPHRINE RELEASE AND PI HYDROLYSIS DURING CELL-GROWTH IN PC12 CELLS SO NEUROSCIENCE LETTERS LA English DT Article DE MUSCARINIC RECEPTOR; NOREPINEPHRINE SECRETION; PHOSPHOINOSITIDE HYDROLYSIS; PC12 CELL; CELL GROWTH ID RECEPTOR AB We have studied the relationships of cell growth to muscarinic stimulation of norepinephrine release and phosphoinositide hydrolysis in the rat pheochromocytoma PC12 cells. The ability of these cells to release norepinephrine in response to muscarinic agonists was maximal during the early phase of exponential growth, and then rapidly decreased to undetectable levels as the cells approached stationary phase. In contrast, muscarinic stimulation of phosphoinositide hydrolysis was low in the early exponential phase of growth, increased to a maximum during late exponential growth and then dramatically dropped in the stationary phase. The number of muscarinic receptors, as measured by antagonist-binding studies, also varied during cell growth with maximal levels at days 2 and 8, corresponding to the maxima in muscarinic-stimulated norepinephrine release and phosphoinositide hydrolysis, respectively. C1 US FDA,CTR BIOL RES & REVIEW,CELLULAR PHYSIOL LAB,BETHESDA,MD 20892. RP TAKASHIMA, A (reprint author), MITSUBISHI KASEI INST LIFE SCI,PROT RES LAB,11 MINAMIOOYA,MACHIDA,TOKYO 194,JAPAN. NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 16 PY 1993 VL 153 IS 1 BP 77 EP 79 DI 10.1016/0304-3940(93)90081-U PG 3 WC Neurosciences SC Neurosciences & Neurology GA KX377 UT WOS:A1993KX37700020 PM 8390033 ER PT J AU RIPPEY, JH WENER, MH HOROSZEWICZ, J STENMAN, UH KLEE, GG BELANGER, A MAXIM, PE GRAVES, H HOWANITZ, J NAKAMURA, RM AF RIPPEY, JH WENER, MH HOROSZEWICZ, J STENMAN, UH KLEE, GG BELANGER, A MAXIM, PE GRAVES, H HOWANITZ, J NAKAMURA, RM TI STANDARDIZATION OF PSA .1. SO CANCER LA English DT Article C1 HELSINKI UNIV HOSP,HELSINKI,FINLAND. VET ADM MED CTR,LOS ANGELES,CA. MILLARD FILLMORE HOSP,BUFFALO,NY 14209. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. UNIV LAVAL,MED CTR,QUEBEC CITY G1K 7P4,QUEBEC,CANADA. US FDA,ROCKVILLE,MD 20857. STANFORD UNIV,MED CTR,SCH MED,STANFORD,CA 94305. SCRIPPS CLIN & RES FDN,LA JOLLA,CA 92037. RP RIPPEY, JH (reprint author), ST LUKES HOSP LAB,WORNALL RD & 44TH ST,KANSAS CITY,MO 64111, USA. NR 1 TC 15 Z9 17 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 0008-543X J9 CANCER JI Cancer PD APR 15 PY 1993 VL 71 IS 8 BP 2678 EP 2678 DI 10.1002/1097-0142(19930415)71:8<2678::AID-CNCR2820710839>3.0.CO;2-4 PG 1 WC Oncology SC Oncology GA KW562 UT WOS:A1993KW56200037 PM 7680951 ER PT J AU BERKOWER, I MURPHY, D AF BERKOWER, I MURPHY, D TI ENZYMATIC LABELING OF BIOACTIVE GP120 OF HIV-1 WITH AFFINITY PURIFIED GALACTOSE-OXIDASE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL,DAPP,IMMUNE RES LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A325 EP A325 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601875 ER PT J AU BOSWELL, C SHAMIM, E STEIN, K AF BOSWELL, C SHAMIM, E STEIN, K TI STRAIN-DEPENDENT RESTRICTED VH AND VL GENE USAGE BY ANTIBACTERIAL LEVAN (BL) MONOCLONAL-ANTIBODIES (MAB) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,OFF BIOL RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A149 EP A149 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600853 ER PT J AU CHU, CC PAUL, WE MAX, EE AF CHU, CC PAUL, WE MAX, EE TI APHIDICOLIN, AN INHIBITOR OF DNA-SYNTHESIS, BLOCKS IMMUNOGLOBULIN CLASS SWITCHING SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,LI,BETHESDA,MD 20892. US FDA CBER,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A171 EP A171 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600984 ER PT J AU CONTI, A BRANDO, C DEBELL, KE ALAVA, MA HOFFMAN, T BONVINI, E AF CONTI, A BRANDO, C DEBELL, KE ALAVA, MA HOFFMAN, T BONVINI, E TI CD3-INDUCED PREFERENTIAL HYDROLYSIS OF POLYPHOSPHOINOSITIDES AND CALCIUM REGULATION OF INOSITOL PHOSPHATE-METABOLISM IN A PERMEABILIZED MURINE T-CELL CLONE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CBER,DIV HEMATOL,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A267 EP A267 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601536 ER PT J AU FELDMAN, GM IGARASHI, K FINBLOOM, DS AF FELDMAN, GM IGARASHI, K FINBLOOM, DS TI CHARACTERIZATION AND PARTIAL-PURIFICATION OF AN INTERFERON-GAMMA-ACTIVATED DNA-BINDING FACTOR THAT RECOGNIZES THE GAMMA-RESPONSE REGION OF THE PROMOTER FOR THE HIGH-AFFINITY FC-GAMMA RECEPTOR GENE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A88 EP A88 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600502 ER PT J AU HAYES, MP AF HAYES, MP TI ENHANCEMENT OF EARLY TYROSINE PHOSPHORYLATION EVENTS FOLLOWING LPS STIMULATION OF IFN-GAMMA-PRIMED HUMAN MONOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A55 EP A55 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600309 ER PT J AU HENRICSON, B ROSENBERG, A AF HENRICSON, B ROSENBERG, A TI INFLAMMATORY RESPONSE GENE-EXPRESSION IN REJECTING MHC CLASS-II DISPARATE GRAFTS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A55 EP A55 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600312 ER PT J AU IGARASHI, K DAVID, M FELDMAN, GM LARNER, AC FINBLOOM, DS AF IGARASHI, K DAVID, M FELDMAN, GM LARNER, AC FINBLOOM, DS TI INVITRO ACTIVATION BY INTERFERON-GAMMA OF A DNA-BINDING FACTOR THAT RECOGNIZES THE GAMMA RESPONSE REGION OF THE FC-GAMMA-RI PROMOTER REQUIRES A MEMBRANE-ASSOCIATED TYROSINE KINASE AND IS MIMICKED BY VANADATE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A205 EP A205 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601183 ER PT J AU MANDLER, R CHU, CC PAUL, WE MAX, EE SNAPPER, CM AF MANDLER, R CHU, CC PAUL, WE MAX, EE SNAPPER, CM TI IL-5 INDUCES S-MU-S-GAMMA-1 DNA REARRANGEMENT BY B-CELLS ACTIVATED WITH DEXTRAN-LINKED ANTI-IGD ANTIBODIES AND IL-4 - A 3 SIGNAL MODEL FOR IG CLASS SWITCHING SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 USUHS,BETHESDA,MD 20814. NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A171 EP A171 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600986 ER PT J AU MCINTYRE, TM KLINMAN, DR ROTHMAN, P LUGO, M DASCH, JR MOND, JJ SNAPPER, CM AF MCINTYRE, TM KLINMAN, DR ROTHMAN, P LUGO, M DASCH, JR MOND, JJ SNAPPER, CM TI TGF-BETA-1 SELECTIVELY STIMULATES IGG2B SECRETION BY LPS-ACTIVATED MURINE B-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 USUHS,BETHESDA,MD 20814. US FDA,BETHESDA,MD 20014. COLUMBIA UNIV,NEW YORK,NY 10027. CELTRIX PHARMACEUT,SANTA CLARA,CA 95054. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A184 EP A184 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601060 ER PT J AU MYERS, MJ FARRELL, DE HENDERSON, M AF MYERS, MJ FARRELL, DE HENDERSON, M TI OXYTETRACYCLINE (OTC) INDUCED SUPPRESSION OF BOVINE AND MURINE MONONUCLEAR CELL FUNCTIONS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,BELTSVILLE,MD 20705. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A132 EP A132 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600758 ER PT J AU NORCROSS, MA YANAGISHITA, M RODERIQUEZ, G BOUHABIB, D ORAVECZ, T HASCALL, V PATEL, M AF NORCROSS, MA YANAGISHITA, M RODERIQUEZ, G BOUHABIB, D ORAVECZ, T HASCALL, V PATEL, M TI CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCAN MEDIATES HIV-1 INFECTION OF CD4+ T-CELL LINES SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. US FDA,CBER,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A243 EP A243 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601404 ER PT J AU ORAVECZ, T NORCROSS, MA AF ORAVECZ, T NORCROSS, MA TI COSTIMULATORY PROPERTIES OF THE HUMAN CD4 MOLECULE - ENHANCEMENT OF CD3-INDUCED T-CELL ACTIVATION BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-I THROUGH VIRAL ENVELOPE GLYCOPROTEIN GP120 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,DIV HEMATOL PROD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A103 EP A103 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600589 ER PT J AU RAYBOURNE, R ROTH, G WILLIAMS, K FUKAZAWA, T YU, D AF RAYBOURNE, R ROTH, G WILLIAMS, K FUKAZAWA, T YU, D TI REACTIVITY OF AN ANTI-HLA-B27 MONOCLONAL-ANTIBODY IS INFLUENCED BY PEPTIDES BOUND TO THE CLASS-I MOLECULE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, LAUREL, MD 20708 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA 90024 USA. NR 1 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A39 EP A39 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600219 ER PT J AU TAGA, K CHERNEY, B TOSATO, G AF TAGA, K CHERNEY, B TOSATO, G TI HUMAN IL-10 AND VIRAL IL-10 PREVENT THE APOPTOSIS OF IL-2-DEPENDENT T-LYMPHOCYTES INDUCED BY IL-2 DEPRIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 15 PY 1993 VL 150 IS 8 BP A11 EP A11 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95600056 ER PT J AU TOSATO, G SGADARI, C TAGA, K LOVE, LA BATHIA, K AF TOSATO, G SGADARI, C TAGA, K LOVE, LA BATHIA, K TI REGRESSION OF EXPERIMENTAL BURKITTS-LYMPHOMA INDUCED BY EBV-IMMORTALIZED B-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20892. NCI,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 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 1993 VL 150 IS 8 BP A309 EP A309 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601779 ER PT J AU YAMAUCHI, A BLOOM, ET AF YAMAUCHI, A BLOOM, ET TI OXIDATION-REDUCTION CONDITIONS REGULATE IL-2-ACTIVATION OF HUMAN NK CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 1993 VL 150 IS 8 BP A301 EP A301 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601736 ER PT J AU ZAITSEVA, M GOLDING, H GOLDING, B AF ZAITSEVA, M GOLDING, H GOLDING, B TI BRUCELLA-ABORTUS, A POTENTIAL CARRIER FOR HUMAN VACCINES, INDUCES TH1-LIKE CYTOKINES IN HUMAN T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA,CBER,DIV UIROL,BETHESDA,MD 20892. US FDA,CBER,DIV HEMATOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 APR 15 PY 1993 VL 150 IS 8 BP A201 EP A201 PN 2 PG 1 WC Immunology SC Immunology GA KX956 UT WOS:A1993KX95601158 ER PT J AU HUNG, HMJ AF HUNG, HMJ TI 2-STAGE TESTS FOR STUDYING MONOTHERAPY AND COMBINATION THERAPY IN 2-BY-2 FACTORIAL TRIALS SO STATISTICS IN MEDICINE LA English DT Article ID CLINICAL-TRIALS; DESIGNS AB Two-stage testing involves a preliminary test of a nuisance parameter prior to testing a main hypothesis. In a two-by-two factorial trial, the treatment interaction is the nuisance to the inference about the efficacy of one of the treatments given alone. In comparing a combination therapy to both of its component therapies, the nuisance parameter is the difference in the component effects. When the preliminary test is an integral part of inference about the main parameter, the actual level of significance for the two-stage test procedure can be much higher than the desired nominal level. If one places no restriction on the value of the nuisance parameter, then any two-stage test with its significance level properly controlled has undesirable properties. This applies to comparative studies of combination agents relative to the component agents. When the interaction with an ineffective treatment is null, two-stage testing may have some power advantage for assessing monotherapy efficacy. RP HUNG, HMJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV BIOMETR,STAT EVALUAT & RES BRANCH,ROCKVILLE,MD 20857, USA. NR 11 TC 6 Z9 6 U1 0 U2 3 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 15 PY 1993 VL 12 IS 7 BP 645 EP 660 DI 10.1002/sim.4780120704 PG 16 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 KZ509 UT WOS:A1993KZ50900003 PM 8511441 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI CHOLESTEROL TEST KIT TO BE AVAILABLE OVER-THE-COUNTER FOR HOME USE 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 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 1993 VL 269 IS 14 BP 1776 EP 1776 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KW250 UT WOS:A1993KW25000007 PM 8384667 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI SUMATRIPTAN APPROVED FOR MIGRAINE HEADACHE PAIN 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 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 1993 VL 269 IS 14 BP 1776 EP 1776 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KW250 UT WOS:A1993KW25000008 PM 8384667 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI USER FRIENDLY REPORTING OF PROBLEMS WITH MEDICATIONS AND MEDICAL 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 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 14 PY 1993 VL 269 IS 14 BP 1776 EP 1776 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KW250 UT WOS:A1993KW25000006 PM 8384667 ER PT J AU DAVIS, VM BAILEY, JE AF DAVIS, VM BAILEY, JE TI CHEMICAL-REDUCTION OF FD-AND-C YELLOW NO 5 TO DETERMINE COMBINED BENZIDINE SO JOURNAL OF CHROMATOGRAPHY LA English DT Note ID UNSULFONATED AROMATIC-AMINES; DIAZOTIZATION AB Data are presented suggesting the presence of the aromatic amine benzidine as a combined impurity in the regulated color additive FD&C Yellow No. 5. The benzidine exists as an azo-dye constituent that forms from free benzidine impurities introduced during the manufacture of the color additive. The presence of combined benzidine is ascertained by sodium dithionite reduction of the azo bonds in the commercial color additive. The resulting reduction products are extracted with chloroform, and the liberated benzidine is determined by high-performance liquid chromatography (HPLC). Tle levels of benzidine determined by HPLC exceed those levels of benzidine accounted for by direct determination of free aromatic amines in the unreduced color. C1 US FDA,DIV COLORS & COSMET,WASHINGTON,DC 20204. RP DAVIS, VM (reprint author), US FDA,DIV TOXICOL STUDIES,WASHINGTON,DC 20204, USA. NR 7 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD APR 9 PY 1993 VL 635 IS 1 BP 160 EP 164 DI 10.1016/0021-9673(93)83128-F PG 5 WC Chemistry, Analytical SC Chemistry GA KY048 UT WOS:A1993KY04800019 PM 8491830 ER PT J AU HAZLET, TK TANKERSLEY, DL AF HAZLET, TK TANKERSLEY, DL TI POSSIBLE INCOMPATIBILITIES WITH IMMUNE GLOBULIN FOR IV USE SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter C1 US FDA,CTR BIOL LAB,PLASMA DERIVAT,BETHESDA,MD 20892. RP HAZLET, TK (reprint author), CALIF DEPT HLTH SERV,FOOD & DRUG BRANCH,601 N 7TH ST,SACRAMENTO,CA 95814, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD APR PY 1993 VL 50 IS 4 BP 654 EP & PG 0 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KV288 UT WOS:A1993KV28800005 PM 8470675 ER PT J AU HARRISYOUNG, L TAMPLIN, ML FISHER, WS MASON, JW AF HARRISYOUNG, L TAMPLIN, ML FISHER, WS MASON, JW TI EFFECTS OF PHYSICOCHEMICAL FACTORS AND BACTERIAL COLONY MORPHOTYPE ON ASSOCIATION OF VIBRIO-VULNIFICUS WITH HEMOCYTES OF CRASSOSTREA-VIRGINICA SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID PHAGOCYTOSIS; OYSTER; SERUM; AGGLUTINATION AB Vibrio vulnificus is a naturally occurring marine bacterium that causes invasive disease of immunocompromised humans following the consumption of raw oysters. It is a component of the natural microbiota of Gulf Coast estuaries and has been found to inhabit tissues of oysters, Crassostrea virginica (Gmelin 1791). The interaction of V. vulnificus with oyster host defenses has not been reported in detail. We examined the interaction of V. vulnificus with phagocytic oyster hemocytes as a function of time, temperature, bacterial concentration, pretreatment with hemolymph, and V. vulnificus translucent and opaque colony morphotypes. Within these experimental parameters, the results showed that the association of V. vulnificus with hemocytes increased with time, temperature, and initial V. vulnificus/hemocyte ratio. Pretreatment of V. vulnificus with serum or an increased serum concentration did not enhance V. vulnificus-hemocyte associations, a result suggesting the absence of opsonic activity. More than 50% of hemocytes bound the translucent, avirulent morphotype, whereas 10 to 20% were associated with the opaque, virulent form, a result indicating that the degree of encapsulation was related to resistance to phagocytosis, as previously described for mammalian phagocytes. Understanding these cellular interactions may, in part, explain the persistence of V. vulnificus in oyster tissues and the ecology of V. vulnificus in estuarine environments. C1 UNIV ALABAMA, SCH PUBL HLTH, BIRMINGHAM, AL 35294 USA. US FDA, FISHERY RES BRANCH, DAUPHIN ISL, AL 36528 USA. UNIV FLORIDA, DEPT HOME ECON, GAINESVILLE, FL 32611 USA. US EPA, GULF BREEZE ENVIRONM RES LAB, CTR MARINE & ESTUARINE DIS RES, GULF BREEZE, FL 32561 USA. NR 33 TC 29 Z9 31 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 1993 VL 59 IS 4 BP 1012 EP 1017 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA KV717 UT WOS:A1993KV71700010 PM 16348903 ER PT J AU KLINMAN, DM DELLACQUA, DK CONOVER, J HUPPI, K AF KLINMAN, DM DELLACQUA, DK CONOVER, J HUPPI, K TI VH FAMILY UTILIZATION BY IGG ANTI-DNA SECRETING LYMPHOCYTES DERIVED FROM AUTOIMMUNE MRL-LPR/LPR MICE SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; FILTER-PAPER DISKS; B-CELLS; MURINE LUPUS; NZB/NZW F1-MICE; RENAL-DISEASE; GENE SEGMENTS; AUTOANTIBODIES; ANTIBODIES; STRAINS AB Objective. To evaluate the heterogeneity of the IgG anti-DNA autoantibody response of MRL/lpr mice. Methods. B cell clones were grown on nitrocellulose membranes. Those producing IgG anti-DNA antibodies were identified by a modified enzyme-linked immunospot assay, and their utilization of IgVH genes was determined by hybridization. Results. Four hundred sixty-eight IgG anti-DNA-secreting colonies were derived from 9 autoimmune MRL/lpr mice. Individual VH families contributed to anti-DNA production at a frequency roughly proportional to their representation in the expressed repertoire (except for the more frequent use of VH 7183 and less frequent use of VH 36-60). In individual mice, anti-DNA antibodies were encoded by 2-5 different IgVH families, with no single family constituting more than 27-65% of any animal's anti-DNA response. Conclusion. The IgG anti-DNA response of individual MRL/lpr mice is oligoclonal. C1 NCI,GENET LAB,BETHESDA,MD 20892. RP KLINMAN, DM (reprint author), US FDA,CTR BIOLOG EVALUAT & RES,RETROVIRUS RES LAB,BLDG 29A,ROOM 3DIO,BETHESDA,MD 20892, USA. NR 57 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 1993 VL 36 IS 4 BP 561 EP 568 DI 10.1002/art.1780360418 PG 8 WC Rheumatology SC Rheumatology GA KW026 UT WOS:A1993KW02600017 PM 8457230 ER PT J AU FRUGONI, P PIKE, SE TOSATO, G AF FRUGONI, P PIKE, SE TOSATO, G TI A MECHANISM OF T-CELL REGULATION OF EPSTEIN-BARR-VIRUS LATENCY SO CELLULAR IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; GROWTH-FACTOR; B-CELLS; CYCLOSPORIN-A; VIRAL LATENCY; INVITRO; INTERLEUKIN-6; INFECTION; TRANSPLANTATION; DIFFERENTIATION RP FRUGONI, P (reprint author), NIH,CTR BIOL EVALUAT & RES,BLDG 29,ROOM 505,BETHESDA,MD 20892, USA. NR 36 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR 1 PY 1993 VL 147 IS 2 BP 256 EP 266 DI 10.1006/cimm.1993.1067 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA KU302 UT WOS:A1993KU30200003 PM 8095857 ER PT J AU JONESTIFFANY, LA MEHROTRA, PT HOROHOV, DW SIEGEL, J KOZAK, RW AF JONESTIFFANY, LA MEHROTRA, PT HOROHOV, DW SIEGEL, J KOZAK, RW TI LOW VERSUS HIGH-DENSITY OF IMMOBILIZED ANTI-CD3 INFLUENCES IL-4 REGULATION OF T-CELL IMMUNE-RESPONSES SO CELLULAR IMMUNOLOGY LA English DT Article ID STIMULATORY FACTOR-I; HUMAN INTERLEUKIN-2 RECEPTOR; HUMAN B-CELLS; GROWTH-FACTOR; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; UP-REGULATION; KILLER CELLS; PROLIFERATION; EXPRESSION RP JONESTIFFANY, LA (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892, USA. NR 41 TC 2 Z9 2 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 APR 1 PY 1993 VL 147 IS 2 BP 425 EP 437 DI 10.1006/cimm.1993.1081 PG 13 WC Cell Biology; Immunology SC Cell Biology; Immunology GA KU302 UT WOS:A1993KU30200017 PM 8453680 ER PT J AU ZHANG, J YU, ZX HILBERT, SL YAMAGUCHI, M CHADWICK, DP HERMAN, EH FERRANS, VJ AF ZHANG, J YU, ZX HILBERT, SL YAMAGUCHI, M CHADWICK, DP HERMAN, EH FERRANS, VJ TI CARDIOTOXICITY OF HUMAN RECOMBINANT INTERLEUKIN-2 IN RATS - A MORPHOLOGICAL-STUDY SO CIRCULATION LA English DT Article DE MYOCARDITIS; MYOCARDIAL NECROSIS; LYMPHOCYTES; CELLS, ENDOTHELIAL ID HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER CELLS; VASCULAR LEAK SYNDROME; TUMOR NECROSIS FACTOR; CYTO-TOXICITY; MONOCLONAL ANTIBODY; ENDOTHELIAL INJURY; LYMPHOCYTES; MYOCARDITIS; THERAPY AB Background. One of the side effects of interleukin 2 (IL-2) cancer immunotherapy in humans is the vascular leak syndrome, which is frequently associated with depression of myocardial function, myocarditis, and myocardial necrosis. Methods and Results. To investigate this cardiotoxicity, IL-2 (three doses of 5 x 10(5) Cetus units/day i.p.) was given to rats for 2, 3, or 5 days. Heart, lung, liver, spleen, and kidney tissues were studied by light and electron microscopy and with immunoperoxidase techniques. Cardiac changes consisted of focal lymphocytic and eosinophilic infiltration, myocyte vacuolization, myofibrillar loss, and necrosis. Ultrastructural alterations included swelling of endothelial cells, with dissociation of intercellular junctions, migration of lymphocytes into the interstitium, and interstitial hemorrhage and edema. Close contact between infiltrating lymphocytes, particularly large granular lymphocytes, and cardiac myocytes was often observed in areas of tissue damage. All lesions were more severe on day 5 than on days 2 and 3. Immunoperoxidase stains demonstrated asialo GM1 ganglioside antibody-positive, granular lymphocytes to be much more frequent in myocardium of IL-2-treated rats than in that of control rats. Conclusions. Although we cannot exclude the possibility of a direct toxic effect of IL-2 on myocytes, our observation's suggest that the myocardial damage produced by this agent is triggered by IL-2-activated lymphocytes that exert cytolytic effects, first on endothelial cells and then on cardiac myocytes, thus producing lesions that involve both the cardiac microcirculation and the muscle cells. C1 NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N240,BETHESDA,MD 20892. US FDA,DIV RES & TESTING,WASHINGTON,DC 20204. US FDA,CTR DEVICES & RADIOL HLTH,WASHINGTON,DC 20204. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 60 TC 27 Z9 28 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR PY 1993 VL 87 IS 4 BP 1340 EP 1353 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KW422 UT WOS:A1993KW42200029 PM 8462156 ER PT J AU HALE, VG BASHAW, ED AF HALE, VG BASHAW, ED TI PHARMACOKINETICS OF OXAPROZIN SO CLINICAL PHARMACY LA English DT Letter RP HALE, VG (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0278-2677 J9 CLIN PHARMACY PD APR PY 1993 VL 12 IS 4 BP 255 EP 256 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KV232 UT WOS:A1993KV23200001 PM 8458176 ER PT J AU DEBINSKI, W PURI, RK PASTAN, I AF DEBINSKI, W PURI, RK PASTAN, I TI CHIMERIC TOXIN COMPOSED OF HUMAN INTERLEUKIN-4 AND PSEUDOMONAS EXOTOXIN IS AN ACTIVE ANTITUMOR AGENT INVIVO SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NCI,DCBDC,LMB,BETHESDA,MD 20892. US FDA,CBER,DCB,BETHESDA,MD 20014. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1993 VL 41 IS 2 BP A276 EP A276 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KW761 UT WOS:A1993KW76100891 ER PT J AU HORN, TD MORISON, WL FARZADEGAN, H ZMUDZKA, BZ BEER, JZ AF HORN, TD MORISON, WL FARZADEGAN, H ZMUDZKA, BZ BEER, JZ TI THE EFFECTS OF ULTRAVIOLET-RADIATION ON HIV IN HUMANS - A PILOT-STUDY SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,DEPT DERMATOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD 21218. US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. US FDA,CTR DEVICES & RADIOL HLTH,BALTIMORE,MD. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1993 VL 41 IS 2 BP A502 EP A502 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KW761 UT WOS:A1993KW76102217 ER PT J AU JONES, K MCKNIGHT, JLC MCWILLIAMS, P TOSATO, G AF JONES, K MCKNIGHT, JLC MCWILLIAMS, P TOSATO, G TI HIGH-LEVEL IL-6 PRODUCTION BY POST TRANSPLANT LYMPHOPROLIFERATIVE DISEASE (PTLD) TISSUES SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20014. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15260. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1993 VL 41 IS 2 BP A242 EP A242 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KW761 UT WOS:A1993KW76100706 ER PT J AU MAJEWSKI, S MARCZAK, M SZMURLO, A RUDNICKA, L KORNHAUSER, A MALEJCZYK, M BOLLAG, W JABLONSKA, S AF MAJEWSKI, S MARCZAK, M SZMURLO, A RUDNICKA, L KORNHAUSER, A MALEJCZYK, M BOLLAG, W JABLONSKA, S TI INHIBITION OF TUMOR-INDUCED ANGIOGENESIS BY SYSTEMIC ADMINISTRATION OF RETINOIDS AND BETA-CAROTENE IN MICE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 WARSAW ACAD MED & HOSP,DEPT DERMATOL,WARSAW,POLAND. US FDA,DEPT SKIN TOXICOL,WASHINGTON,DC 20204. F HOFFMANN LA ROCHE & CO LTD,PHARMACEUT RES,CH-4002 BASEL,SWITZERLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1993 VL 41 IS 2 BP A509 EP A509 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KW761 UT WOS:A1993KW76102262 ER PT J AU PERSHING, LK BAKHTIAN, S PONCELET, C CORLETT, J SHAH, VP AF PERSHING, LK BAKHTIAN, S PONCELET, C CORLETT, J SHAH, VP TI DISPARITY BETWEEN THE PHARMACOKINETIC AND PHARMACODYNAMIC DOSE-RESPONSE OF TRIAMCINOLONE ACETONIDE CREAM FORMULATIONS IN HUMANS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV UTAH,DIV DERMATOL,SALT LAKE CITY,UT 84132. US FDA,OFF GENER DRUGS,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1993 VL 41 IS 2 BP A498 EP A498 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KW761 UT WOS:A1993KW76102195 ER PT J AU TAQA, K CHERNEY, B TOSATO, G AF TAQA, K CHERNEY, B TOSATO, G TI HUMAN IL-10 PREVENTS THE APOPTOSIS OF IL-2-DEPENDENT T-LYMPHOCYTES INDUCED BY IL-2 DEPRIVATION SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1993 VL 41 IS 2 BP A185 EP A185 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KW761 UT WOS:A1993KW76100408 ER PT J AU WILSON, KC FELDMAN, GM IGARASHI, K FINBLOOM, DS AF WILSON, KC FELDMAN, GM IGARASHI, K FINBLOOM, DS TI CHARACTERIZATION OF AN INTERFERON-GAMMA-ACTIVATED DNA-BINDING FACTOR THAT RECOGNIZES THE GAMMA-RESPONSE REGION OF THE PROMOTER FOR THE HIGH-AFFINITY FC-GAMMA RECEPTOR GENE SO CLINICAL RESEARCH 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 SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD APR PY 1993 VL 41 IS 2 BP A185 EP A185 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KW761 UT WOS:A1993KW76100407 ER PT J AU ARCINIEGA, JL HEWLETT, EL EDWARDS, KM BURNS, DL AF ARCINIEGA, JL HEWLETT, EL EDWARDS, KM BURNS, DL TI ANTIBODIES TO BORDETELLA-PERTUSSIS ADENYLATE-CYCLASE TOXIN IN NEONATAL AND MATERNAL SERA SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE BORDETELLA-PERTUSSIS ADENYLATE CYCLASE TOXIN; PERTUSSIS; WHOOPING COUGH; ANTIBODIES TO BORDETELLA-PERTUSSIS IN NEONATES; ANTIBODIES TO ESCHERICHIA-COLI ALPHA-HEMOLYSIN IN NEONATES ID VIRULENCE FACTORS; ESCHERICHIA-COLI; IDENTIFICATION; INFECTION; HEMOLYSIN; PROTEINS AB To investigate the high prevalence among infants of antibodies to Bordetella pertussis adenylate cyclase toxin (ACT), cord-blood sera were examined for antibodies to ACT, filamentous hemagglutinin (FHA) and pertussis toxin (PT) using immunoblot analysis. Antibodies reactive with ACT were the most prevalent in neonatal sera. Similar reactivity of IgG with ACT was found in each sample of a given neonatal-maternal pair, yet IgM reactive with ACT was virtually absent in neonatal sera, suggesting that antibodies to ACT are maternally derived. Antibodies to ACT might come from infection or childhood vaccination of the mothers since pertussis vaccines from all US manufacturers elicited antibodies to ACT in mice. Alternatively, these antibodies may have been elicited by a cross-reactive antigen such as Escherichia coli alpha-hemolysin, since all of the neonatal and maternal sera contained antibodies reactive with alpha-hemolysin. C1 UNIV VIRGINIA,MED CTR,SCH MED,CHARLOTTESVILLE,VA 22901. VANDERBILT UNIV,MED CTR,SCH MED,DEPT PEDIAT,DIV INFECT DIS,NASHVILLE,TN 37232. RP ARCINIEGA, JL (reprint author), US FDA,CTR BIOL EVALUAT & RES,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [R01-AI-18000, N01-AI-52594] NR 15 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD APR PY 1993 VL 6 IS 4 BP 325 EP 330 DI 10.1111/j.1574-695X.1993.tb00345.x PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA KZ758 UT WOS:A1993KZ75800009 PM 8499896 ER PT J AU SAPIENZA, PP IKEDA, GJ WARR, PI PLUMMER, SI DAILEY, RE LIN, CS AF SAPIENZA, PP IKEDA, GJ WARR, PI PLUMMER, SI DAILEY, RE LIN, CS TI TISSUE DISTRIBUTION AND EXCRETION OF C-14-LABELED CINNAMIC ALDEHYDE FOLLOWING SINGLE AND MULTIPLE ORAL-ADMINISTRATION IN MALE FISCHER-344 RATS SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID FEMALE RATS; ACIDS; URINE AB C-14-labelled cinnamic aldehyde (CNMA) was given as a single oral dose, or 24 hr after multiple oral administration of non-radioactive CNMA for 7 days at 24-hr intervals, to male Fischer 344 rats at dose levels of 5, 50 or 500 mg/kg body weight. Residues of radioactive CNMA were measured. After the single dose radioactivity was distributed primarily in the gastro-intestinal tract, the kidneys and the liver of the rats. The radiolabel was excreted mainly in the urine, and at 24 hr 85.1, 84.2 and 81.2% of the administered radiolabel was recovered in the urine at the 5, 50 and 500 mg/kg dose levels, respectively. Faecal excretion of radiolabel at 24 hr for the 5, 50 and 500 mg/kg doses was 5.1, 4.0 and 3.2% of the administered dose, respectively. At all dose levels, a small amount of the dose was distributed to the fat and was easily measured in animals killed 3 days after dosing at the 50 or 500 mg/kg dose levels. Following multiple oral administration, similar tissue distribution and excretion patterns of radiolabel were found at the three dose levels. After 24 hr the administered radiolabel was distributed mainly to the fat, liver and gastro-intestinal tract. At 24 hr, recoveries of the radiolabel in the urine were 80.4, 80.6 and 81.9% of the dose for the 5, 50 and 500 mg/kg dose levels, respectively. Faecal excretion of radiolabel after multiple dosing at 24 hr accounted for 6.3, 6.9 and 4.5% of the administered radioactivity at the 5, 50 and 500 mg/kg dose levels, respectively. The major metabolic pathway of CNMA for all single and the 5 and 50 mg/kg multiple dose levels in this species of rat was found to be degradation to benzoic acid through beta-oxidation and excretion in the urine mainly as hippuric acid, with much smaller amounts of benzoic and cinnamic acids. At the multiple dose level of 500 mg/kg, benzoic acid was the major urinary metabolite, indicating that in the Fischer 344 male rat at this relatively high oral dose level the detoxification of CNMA proceeds differently and an alternative metabolic pathway is proposed. RP SAPIENZA, PP (reprint author), US FDA,DIV TOXICOL STUDIES,WASHINGTON,DC 20204, USA. NR 17 TC 12 Z9 18 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 1993 VL 31 IS 4 BP 253 EP 261 DI 10.1016/0278-6915(93)90075-A PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA LC176 UT WOS:A1993LC17600003 PM 8477915 ER PT J AU JENKINS, MLY AF JENKINS, MLY TI RESEARCH ISSUES IN EVALUATING FUNCTIONAL FOODS SO FOOD TECHNOLOGY LA English DT Article ID VITAMIN-A; RATS RP JENKINS, MLY (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV SCI & APPL TECHNOL HFS-175,OFF FOOD LABELING,LAUREL,MD 20708, USA. NR 18 TC 8 Z9 9 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD APR PY 1993 VL 47 IS 4 BP 76 EP & PG 0 WC Food Science & Technology SC Food Science & Technology GA KX056 UT WOS:A1993KX05600015 ER PT J AU GREENMAN, DL ALLABEN, WT BURGER, GT KODELL, RL AF GREENMAN, DL ALLABEN, WT BURGER, GT KODELL, RL TI BIOASSAY FOR CARCINOGENICITY OF ROTENONE IN FEMALE WISTAR RATS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article RP GREENMAN, DL (reprint author), NATL CTR TOXICOL RES,OFF SCI COORDINAT,HFT-30,JEFFERSON,AR 72079, USA. NR 29 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD APR PY 1993 VL 20 IS 3 BP 383 EP 390 DI 10.1006/faat.1993.1049 PG 8 WC Toxicology SC Toxicology GA KZ304 UT WOS:A1993KZ30400015 PM 8504913 ER PT J AU CHOWDHURY, P DOI, R LYNNCOOK, BD MONTAGUE, DC CHANG, LW RAYFORD, PL AF CHOWDHURY, P DOI, R LYNNCOOK, BD MONTAGUE, DC CHANG, LW RAYFORD, PL TI INHALATION OF NICOTINE ENHANCES MUTANT P21 PROTEIN EXPRESSION OF RAT PANCREATIC ACINAR-CELLS IN CONJUNCTION WITH PATHOLOGICAL-CHANGES SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1993 VL 104 IS 4 SU S BP A392 EP A392 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KX957 UT WOS:A1993KX95701555 ER PT J AU FRANKEL, W SATCHITHANANDAM, S SINGH, A ZHANG, W BAIN, A KLURFELD, D ROMBEAU, J AF FRANKEL, W SATCHITHANANDAM, S SINGH, A ZHANG, W BAIN, A KLURFELD, D ROMBEAU, J TI OAT FIBER DECREASES BACTERIAL TRANSLOCATION TO MESENTERIC LYMPH-NODES WITHOUT INCREASING INTESTINAL MUCIN IN A RAT MODEL OF NUTRITIONAL SUPPORT SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 HOSP UNIV PENN,HARRISON DEPT SURG,PHILADELPHIA,PA 19104. WAYNE STATE UNIV,DETROIT,MI 48202. FDA,LAUREL,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1993 VL 104 IS 4 SU S BP A621 EP A621 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KX957 UT WOS:A1993KX95702468 ER PT J AU HOFFENBERG, EJ OFFIT, PA HILL, N SANTOS, N GOUVEA, V AF HOFFENBERG, EJ OFFIT, PA HILL, N SANTOS, N GOUVEA, V TI PRIMARY SYMPTOMATIC ROTAVIRUS INFECTION ELICITS NEUTRALIZING ANTIBODIES AGAINST OUTER CAPSID PROTEIN-VP4 AND CIRCULATING VIRUS-SPECIFIC T-HELPER CELLS SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV PENN,CHILDRENS HOSP,SCH MED,DIV GASTROENTEROL,PHILADELPHIA,PA 19104. UNIV PENN,CHILDRENS HOSP,SCH MED,DIV INFECT DIS,PHILADELPHIA,PA 19104. US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1993 VL 104 IS 4 SU S BP A713 EP A713 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KX957 UT WOS:A1993KX95702833 ER PT J AU BAO, JZ DAVIS, CC SCHMUKLER, RE AF BAO, JZ DAVIS, CC SCHMUKLER, RE TI IMPEDANCE SPECTROSCOPY OF HUMAN ERYTHROCYTES - SYSTEM CALIBRATION AND NONLINEAR MODELING SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID CONSTANT-PHASE-ANGLE; FREQUENCY-DOMAIN; CELLS; MEMBRANE; INTERFACE AB We present in detail our impedance measurement method, the cell embedding technique, for human erythrocytes, and an accurate calibration procedure for a true four-electrode impedance measurement system. This technique with the calibration procedure gives reliable impedance measurements over a wide frequency range-1 Hz to 10 MHz. To achieve high sensitivity in this frequency range, we embed the cells in the pores of a Nuclepore filter. The calibration procedure assumes that the measurement system is linear, and requires measurement of three reference impedances. The reliability of this procedure is demonstrated with various RC circuits, and application of it to the bio-impedancae measurement system eliminates a quasi-dispersion in the high-frequency range, and increases the bandwidth at both the low- and high-frequency ends of the range by about a decade. We model the impedance of the cells embedded within the filter with an equivalent circuit that is consistent with the geometry and interfaces present. The experimental data are fitted to this model by means of a complex nonlinear least squares (CNLS) fit, which simultaneously fits the real and imaginary parts of the impedance with the Levenberg-Marquardt algorithm. The impedance spectra of human erythrocytes are found to display constant-phase-angle (CPA) characteristics. A CPA element is an impedance of the form Z = A/(jomega)alpha, where A is a constant, j = square-root -1, omega is angular frequency, and 0 < alpha < 1. and has been used to describe the ac response of the interface between the cell surface and the external electrolyte solution. Such a CPA element may be related to fractal character of the interface. C1 UNIV MARYLAND,CHEM PHYS PROGRAM,COLL PK,MD 20742. US FDA,CTR DEVICE & RADIOL HLTH,ELECTROPHYS BRANCH,ROCKVILLE,MD 20852. RP BAO, JZ (reprint author), UNIV MARYLAND,DEPT ELECT ENGN,COLL PK,MD 20742, USA. FU PHS HHS [223-84-6038] NR 30 TC 66 Z9 66 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD APR PY 1993 VL 40 IS 4 BP 364 EP 378 DI 10.1109/10.222329 PG 15 WC Engineering, Biomedical SC Engineering GA LN578 UT WOS:A1993LN57800008 PM 8375873 ER PT J AU FRIES, LF WAAG, DM WILLIAMS, JC AF FRIES, LF WAAG, DM WILLIAMS, JC TI SAFETY AND IMMUNOGENICITY IN HUMAN VOLUNTEERS OF A CHLOROFORM-METHANOL RESIDUE VACCINE FOR Q-FEVER SO INFECTION AND IMMUNITY LA English DT Article ID I COXIELLA-BURNETII; PHASE-I; IMMUNITY; MICE; LIPOPOLYSACCHARIDES; SUSCEPTIBILITY; VIRULENCE; ABATTOIRS; CELLS AB Current Q fever vaccines, consisting of Formalin-inactivated phase I whole Coxiella burnetii, are highly efficacious, in preventing disease in high-risk settings but are associated with a risk of unacceptable local reactions in previously immune individuals and require cumbersome preliminary immunologic evaluation of potential vaccinees. A vaccine prepared from the residue of chloroform-methanol extraction of phase I Henzerling strain C. burnetii (CMR) has been shown to be less reactogenic but still immunogenic and protective in small animals and sheep. In a placebo-controlled trial, we immunized 35 healthy adults unscreened for markers of prior C. burnetii immunity with a single subcutaneous CMR dose of 30, 60, 120, or 240 mug. None of those receiving the 30- or 600 mug CMR dose and none of the placebo recipients experienced any adverse effects. Five of 15 120-mug dose CMR recipients complained of transient discomfort in the inoculated arm; erythema or induration of greater-than-or-equal-to 100 mm2 was noted in three and four, respectively, and two had malaise and low-grade fever (< 101-degrees-F, orally). No 240-mug dose vaccinee reported limb discomfort, but 7 of 10 had erythema and/or induration of greater-than-or-equal-to 100 mm2 (P < 0.001 versus placebo). Two reported malaise, and one had low-grade fever. All adverse effects were self-limited. Serum immunoglobulin M responses were optimally detected with CMR antigen and occurred in 50, 60, 73, and 90% of recipients of the 30-, 60-, 120-, and 240-mug doses, respectively; results with phase I whole-cell antigen were similar. Serum immunoglobulin G responses were best detected with phase II antigen and were seen in 20, 20, and 40% of those receiving the 60-, 120-, and 240-mug doses, respectively. Peripheral blood T-cell proliferative responses to (C. burnetii recall antigens were transient and of low magnitude but were seen with CMR antigen in 33% of 120-mug dose recipients and 40% of 240-mug dose recipients. Data from this study and those from comparative-efficacy trials in primates should provide the basis for field trials of the CMR vaccine. C1 USA,MED RES INST INFECT DIS,FREDERICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,DIV BIOL INVEST NEW DRUGS,BETHESDA,MD 20892. RP FRIES, LF (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,CTR IMMUNIZA RES,BALTIMORE,MD 21205, USA. NR 34 TC 28 Z9 31 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 APR PY 1993 VL 61 IS 4 BP 1251 EP 1258 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KU320 UT WOS:A1993KU32000012 PM 8454328 ER PT J AU AMSBAUGH, DF LI, ZM SHAHIN, RD AF AMSBAUGH, DF LI, ZM SHAHIN, RD TI LONG-LIVED RESPIRATORY IMMUNE-RESPONSE TO FILAMENTOUS HEMAGGLUTININ FOLLOWING BORDETELLA-PERTUSSIS INFECTION SO INFECTION AND IMMUNITY LA English DT Article ID CELLS; ANTIGEN; MICROCULTURE; MACROPHAGES; CLONING; PROTEIN; SYSTEM; GENE; MICE AB Systemic and mucosal B-cell-mediated immune responses to purified filamentous hemagglutinin (FHA) in mice were analyzed at different times following a single respiratory infection with Bordetella pertussis. Serum immunoglobulin G (IgG) anti-FHA and respiratory IgG and IgA anti-FHA antibodies were first detected at 3 weeks postinfection, reached high levels by 8 weeks postinfection, and remained at high levels 12 to 32 weeks postinfection. FHA-specific B lymphocytes isolated from the spleens or lungs of uninfected control mice or mice convalescing from B. pertussis respiratory infection were analyzed in limiting-dilution cultures. Analysis of culture supernatants for the production of antibodies to FHA revealed an increased frequency of FHA-specific B cells of both the IgG- and the IgA-secreting classes in the lungs and tracheas of aerosol-challenged mice; these levels remained high as late as 25 weeks postinfection, compared with those in uninfected controls. No corresponding increase in the frequency of FHA-specific B cells in the spleens of aerosol-infected mice was observed. This long-lasting response observed in cultured cells was radiation resistant, a result suggesting that this response was due to B cells already activated in vivo. Polymerase chain reaction analysis revealed low but detectable levels of B. pertussis chromosomal DNA in 75% of mice tested at 8 weeks postinfection and 37.5% of mice tested at 26 weeks postinfection, at which times high levels of anti-FHA antibody were detected. One explanation for these data may be that, in this animal model, a major adhesin of B. pertussis can persist and interact with components of the immune system to stimulate the production of specific antibody in the respiratory tract many weeks after a single B. pertussis infection. RP AMSBAUGH, DF (reprint author), US FPA,CTR BIOL EVALUAT & RES,PERTUSSIS LAB,BETHESDA,MD 20892, USA. NR 38 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 APR PY 1993 VL 61 IS 4 BP 1447 EP 1452 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KU320 UT WOS:A1993KU32000041 PM 8454349 ER PT J AU FRANZOSO, G HU, PC MELONI, GA BARILE, MF AF FRANZOSO, G HU, PC MELONI, GA BARILE, MF TI THE IMMUNODOMINANT 90-KILODALTON PROTEIN IS LOCALIZED ON THE TERMINAL TIP STRUCTURE OF MYCOPLASMA-PNEUMONIAE SO INFECTION AND IMMUNITY LA English DT Article ID RESPIRATORY EPITHELIUM; NUCLEOTIDE-SEQUENCE; ATTACHMENT PROTEIN; SURFACE PROTEIN; IDENTIFICATION; HEMADSORPTION; ANTIBODIES; VIRULENT; GENE; INHIBITION AB Immunoblot analysis of convalescent-phase sera of experimentally infected chimpanzees or monoclonal antibodies (MAbs) specific to the 90- and 40-kDa proteins of Mycoplasma pneumoniae indicated that both proteins were present in cytadsorbing, pathogenic strains PI-1428, M129, and FH but absent in noncytadsorbing, nonpathogenic strain M129-B176. Adsorption of convalescent-phase chimpanzee sera with virulent strain PI-1428 removed reactivity, whereas adsorption with avirulent strain M129-B176 did not remove reactivity to these two proteins. By using proteolysis and specific MAbs, we demonstrated that the 90- and 40-kDa proteins were surface exposed. Immunoelectron microscopy employing specific MAbs showed that the 90-kDa protein is localized on the terminal tip attachment apparatus. However, the MAb specific for the 40-kDa protein failed to indicate a similar localization. Nevertheless, these data, taken together, indicate that the immunodominant 90- and 40-kDa proteins are surface exposed, are localized on the terminal tip apparatus, and might be involved in the attachment mechanism. C1 US FDA,CTR BIOL EVALUAT & RES,MYCOPLASMA LAB,BETHESDA,MD 20892. UNIV N CAROLINA,SCH MED,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV PADUA,IST MICROBIOL,I-35100 PADUA,ITALY. NR 44 TC 38 Z9 38 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 APR PY 1993 VL 61 IS 4 BP 1523 EP 1530 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KU320 UT WOS:A1993KU32000052 PM 8454358 ER PT J AU CAPUTO, FA MATTES, RD AF CAPUTO, FA MATTES, RD TI HUMAN DIETARY RESPONSES TO PERCEIVED MANIPULATION OF FAT-CONTENT IN A MIDDAY MEAL SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE DIET; FAT; FOOD INTAKE; HUMAN; CALORIC COMPENSATION; ENERGY INTAKE; ENERGY BALANCE AB The influence of knowledge about the macronutrient content of foods on dietary habits is poorly understood. The present study examined dietary responses to manipulations of information about the fat content of a midday meal provided to 17 free-living individuals. Following a one week baseline period, subjects were told that the meal provided each day for three 12-day blocks supplied a greater, lesser or equal amount of fat than their customary midday meal. They recorded dally intake. During the low-fat information period, subjects increased their total dally intake of energy relative to the high-fat period, their energy derived from protein relative to baseline and their energy derived from fat relative to all other periods. Information about the fat content of foods can influence food selection and should be considered when developing dietary interventions aimed at moderating fat intake. C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,JEFFERSON,AR 72079. MONELL CHEM SENSES CTR,PHILADELPHIA,PA 19104. NR 14 TC 43 Z9 43 U1 3 U2 7 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 1993 VL 17 IS 4 BP 237 EP 240 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA KW212 UT WOS:A1993KW21200007 PM 8387972 ER PT J AU RUHL, S PLUZNIK, DH AF RUHL, S PLUZNIK, DH TI DISSOCIATION OF EARLY AND LATE MARKERS OF MURINE MYELOID DIFFERENTIATION BY INTERFERON-GAMMA AND INTERLEUKIN-6 SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID LEUKOCYTE-CONDITIONED MEDIUM; COLONY-STIMULATING FACTOR; IMMEDIATE EARLY RESPONSE; LEUKEMIA-CELL LINE; TERMINAL DIFFERENTIATION; IMMUNE INTERFERON; TRANSCRIPTIONAL REGULATION; MOLECULAR CONTROL; GENE-EXPRESSION; RIBOSOMAL-RNA AB Murine myeloid leukemia M1 cells undergo terminal differentiation to mature macrophages after stimulation with interleukin-6 (IL-6). This process can be monitored by measuring the expression of early markers such as the high affinity receptor for monomeric IgG2a (FcgammaRI) and la antigen followed by late markers such as lysozyme production and finally morphological changes from blast cells to mature macrophages. The same early markers that are expressed on Ml cells after induction with IL-6 are also expressed on monocytic cells after activation with interferon-gamma (IFNgamma). We used IL-6 and IFNgamma to investigate whether the early stages of M1 cell differentiation could be accomplished without commitment of the cells to terminal differentiation. Cytofluorometry shows that the expression of the same early differentiation markers (FcgammaRI and Ia antigen) that are inducible by IL-6 on Ml cells can be induced by IFNgamma as well. However, stimulation with IFNgamma, in contrast to IL-6, does not induce the late differentiation markers such as lysozyme production, phagocytic activity, and morphological changes. Northern analysis supports these findings in that expression of FcgammaRI mRNA is induced by either cytokine, whereas expression of mRNA for lysozyme is inducible by IL-6 only. Nuclear run-on analysis reveals that the changes in steady state mRNA levels of both FcgammaRI and lysozyme are regulated by a transcriptional mechanism. These data suggest that early stages in the process of myeloid differentiation can be separately induced by IFNgamma and thus are independent from the later events induced by IL-6. C1 US FDA,CBER,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 45 TC 18 Z9 18 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD APR PY 1993 VL 155 IS 1 BP 130 EP 138 DI 10.1002/jcp.1041550117 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA KV369 UT WOS:A1993KV36900016 PM 8468358 ER PT J AU GOUVEA, V RAMIREZ, C LI, BG SANTOS, N SAIF, L CLARK, HF HOSHINO, Y AF GOUVEA, V RAMIREZ, C LI, BG SANTOS, N SAIF, L CLARK, HF HOSHINO, Y TI RESTRICTION ENDONUCLEASE ANALYSIS OF THE VP7 GENES OF HUMAN AND ANIMAL ROTAVIRUSES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; SEQUENCE-ANALYSIS; G-SEROTYPE; NEUTRALIZATION; IDENTIFICATION; HYBRIDIZATION; STRAINS; FELINE; ACID AB The vp7 genes of 194 strains of group A rotaviruses representing all known G types were analyzed with three restriction enzymes by direct digestion of amplified cDNA copies or by deduction of the restriction patterns from known sequences. Mammalian rotavirus strains were classified into 28 restriction patterns consisting of combinations of the 6 profiles (s1 to s6) obtained by digestion with Sau96I endonuclease, 9 profiles (h1 to h9) obtained with HaeIII, and 15 profiles (b1 to b15) obtained with BstYI. Digestion with Sau96I and HaeIII identified restriction sites common to all, or almost all, rotavirus strains studied, whereas BstYI was the most discriminating among rotavirus strains. A clear correlation between some restriction patterns or individual profiles and G type and/or host species of origin was found. Several discriminatory restriction sites consisted of type-specific nucleic acid sequences that encoded conserved amino acid residues. Although not directly involved in antigenic diversity, these sites appear to indicate the G type of the isolate. The technique permits rapid comparison of a large number of virus isolates directly from fecal specimens and provides useful markers for investigating the evolution of rotavirus vp7 genes and tracing vaccine virus and interspecies transmission. C1 OHIO STATE UNIV,OHIO AGR RES & DEV CTR,WOOSTER,OH 44691. CHILDRENS HOSP PHILADELPHIA,DIV INFECT DIS,PHILADELPHIA,PA 19104. NIH,INFECT DIS LAB,BETHESDA,MD 20892. RP GOUVEA, V (reprint author), US FDA,DIV MICROBIOL,WASHINGTON,DC 20204, USA. RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 26 TC 44 Z9 44 U1 0 U2 2 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 APR PY 1993 VL 31 IS 4 BP 917 EP 923 PG 7 WC Microbiology SC Microbiology GA KT445 UT WOS:A1993KT44500028 PM 8385152 ER PT J AU MCINTYRE, TM KLINMAN, DR ROTHMAN, P LUGO, M DASCH, JR MOND, JJ SNAPPER, CM AF MCINTYRE, TM KLINMAN, DR ROTHMAN, P LUGO, M DASCH, JR MOND, JJ SNAPPER, CM TI TRANSFORMING GROWTH FACTOR-BETA(1) SELECTIVITY STIMULATES IMMUNOGLOBULIN-G2B SECRETION BY LIPOPOLYSACCHARIDE-ACTIVATED MURINE B-CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GERM-LINE TRANSCRIPTS; ANTI-IG ANTIBODIES; FACTOR TYPE-BETA; LYMPHOCYTES-B; INTERFERON-GAMMA; SYNOVIAL-FLUID; EXPRESSION; INVITRO; SWITCH; PURIFICATION AB Bacterial lipopolysaccharide (LPS) has been reported to induce immunoglobulin (Ig)G2b class switching, yet we observed strain differences in IgG2b secretion in response to this mitogen. Specifically, BALB/c B cells, unlike those from DBA/2, synthesized relatively low amounts of IgG2b relative to IgG3, IgG1, or IgM. This report demonstrates that transforming growth factor (TGF)beta1, previously shown to induce IgA class switching, selectively stimulates IgG2b secretion by BALB/c resting B cells activated with LPS. This activity was specifically reversed with a neutralizing anti-TGF-beta1 antibody. The ability of TGF-beta1 to act directly on highly purified membrane (m)IgM+mIgG2b- cells to stimulate IgG2b production, stimulate an increase in IgG2b-secreting cells, and selectively increase the steady-state levels of germline gamma2b RNA, suggests that it promotes IgG2b class switching. In this regard, addition of anti-TGF-beta antibody to cultures of DBA/2-derived resting B cells activated by LPS, alone, led to selective reduction in IgG2b secretion, indicating that endogenous TGF-beta1 accounts for the high IgG2b secretory response observed in that strain. Finally, TGF-beta1 failed to stimulate IgG2b secretion by B cells activated with dextran-conjugated anti-IgD antibody. We propose that TGF-beta1 is a switch factor for the murine IgG2b subclass for appropriately activated B cells. In combination with other data, this would show that all six non-IgM, non-IgD isotypes in the mouse can be selectively induced by specific cytokines. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. CELTRIX PHARMACEUT,SANTA CLARA,CA 94054. FU NIAID NIH HHS [AI-24273, AI-27465] NR 36 TC 143 Z9 143 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 APR 1 PY 1993 VL 177 IS 4 BP 1031 EP 1037 DI 10.1084/jem.177.4.1031 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KU080 UT WOS:A1993KU08000016 PM 8459202 ER PT J AU ABEYTA, C DEETER, FG KAYSNER, CA STOTT, RF WEKELL, MM AF ABEYTA, C DEETER, FG KAYSNER, CA STOTT, RF WEKELL, MM TI CAMPYLOBACTER-JEJUNI IN A WASHINGTON-STATE SHELLFISH GROWING BED ASSOCIATED WITH ILLNESS SO JOURNAL OF FOOD PROTECTION LA English DT Note ID FETUS SUBSP JEJUNI AB Consumption of raw Pacific oysters (Crassotea gigas) harvested from a Washington State recreational shellfish bed were associated with illness. Illness occurred within 2 d of ingestion of a half-dozen shellstock oysters. Each oyster consist of approximately 20 g of meat. The duration of illness lasted 2 d. Routinely, Campylobacter species have been found in several shellfish beds in the Puget Sound Bay. Its presence in the marine environment appears to be incidental and primarily, comes from wild birds, farm runoff, and sewage bypasses. This paper describes the first reported case of Campylobacter gastroenteritis associated with raw oyster consumption in the State-of Washington. C1 US DEPT HLTH,SHELLFISH PROGRAMS,OLYMPIA,WA 98504. RP ABEYTA, C (reprint author), US FDA,SEAFOOD PROD RES CTR,BOTHELL,WA 98041, USA. NR 15 TC 24 Z9 25 U1 1 U2 2 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2838 SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 1993 VL 56 IS 4 BP 323 EP 325 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA KZ104 UT WOS:A1993KZ10400009 ER PT J AU PERSHING, LK BAKHTIAN, S PONCELET, C CORLETT, J SHAH, VP AF PERSHING, LK BAKHTIAN, S PONCELET, C CORLETT, J SHAH, VP TI DISPARITY BETWEEN THE PHARMACOKINETIC AND PHARMACODYNAMIC DOSE-RESPONSE OF TRIAMCINOLONE ACETONIDE CREAM FORMULATIONS IN HUMANS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV UTAH,DIV DERMATOL,SALT LAKE CITY,UT 84132. US FDA,OFF GENER DRUGS,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1993 VL 100 IS 4 BP 591 EP 591 PG 1 WC Dermatology SC Dermatology GA KW395 UT WOS:A1993KW39500915 ER PT J AU HORN, TD MORISON, WL FARZADEGAN, H ZMUDZKA, BZ BEER, JZ AF HORN, TD MORISON, WL FARZADEGAN, H ZMUDZKA, BZ BEER, JZ TI THE EFFECTS OF ULTRAVIOLET-RADIATION ON HIV IN HUMANS - A PILOT-STUDY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,DEPT DERMATOL,BALTIMORE,MD 21218. US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1993 VL 100 IS 4 BP 595 EP 595 PG 1 WC Dermatology SC Dermatology GA KW395 UT WOS:A1993KW39500941 ER PT J AU MAJEWSKI, S MARCZAK, M SZMURLO, A RUDNICKA, L KORNHAUSER, A MALEJCZYK, M BOLLAG, W JABLONSKA, S AF MAJEWSKI, S MARCZAK, M SZMURLO, A RUDNICKA, L KORNHAUSER, A MALEJCZYK, M BOLLAG, W JABLONSKA, S TI INHIBITION OF TUMOR-INDUCED ANGIOGENESIS BY SYSTEMIC ADMINISTRATION OF RETINOIDS AND BETA-CAROTENE IN MICE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 WARSAW ACAD MED & HOSP,DEPT DERMATOL,WARSAW,POLAND. US FDA,DEPT SKIN TOXICOL,WASHINGTON,DC 20204. HOFFMAN LA ROCHE INC,PHARMACEUT RES,BASEL,SWITZERLAND. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1993 VL 100 IS 4 BP 602 EP 602 PG 1 WC Dermatology SC Dermatology GA KW395 UT WOS:A1993KW39500983 ER PT J AU PASTAKIA, KB TERLE, D PRODOUZ, KN AF PASTAKIA, KB TERLE, D PRODOUZ, KN TI PENICILLIN-INDUCED DYSFUNCTION OF PLATELET MEMBRANE-GLYCOPROTEINS SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID IIB-IIIA COMPLEX; IB; THROMBIN; ACTIVATION; PROTEINS; IX; INVITRO; SURFACE; INVIVO; BINDING AB We examined the effects of the beta-lactam antibiotic penicillin G on platelet function and on specific membrane glycoproteins in vitro. Platelet concentrates exposed to 3 to 10 mmol/L penicillin for 48 hours showed irreversible inhibition of aggregation by thrombin in washed platelets after removal of the antibiotic. Although a brief 15-minute exposure to similar doses of penicillin also inhibited thrombin aggregation, the inhibition was reversed on removal of the penicillin by washing. Aggregation activity was also restored to normal levels by stimulation with high thrombin concentrations (>0.4 U/ml). Results of the aggregation studies led us to examine how penicillin affects platelet membrane proteins. Membranes isolated after 48 hours of exposure of platelet concentrates to penicillin showed no differences from the control in total protein profiles on sodium dodecylsulfate-polyacrylamide gel electrophoresis or in the glycoprotein Ib or IIb content on immunoblotting. However, flow cytometric analysis with fluorescently labeled monoclonal antibodies revealed that exposure of platelets to penicillin for 15 minutes inhibited thrombin-induced modulations in the glycoproteins Ib, Ib-IX, IIb-IIIa, and P-selectin. These effects were observed with washed platelets and platelets in plasma. Penicillin also inhibited the regulation of expression of glycoproteins Ib-IX and IIb-IIIa in adenosine diphosphate-activated platelets. The inhibitory effects were partially reversed at high agonist concentrations. RP PASTAKIA, KB (reprint author), US FDA,CTR BIOL EVALUAT & RES,BLDG 29,RM 329,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 13 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD APR PY 1993 VL 121 IS 4 BP 546 EP 554 PG 9 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA KV503 UT WOS:A1993KV50300006 PM 8454936 ER PT J AU GREENMAN, DL MORRISSEY, R GAYLOR, DW ALLABEN, WT AF GREENMAN, DL MORRISSEY, R GAYLOR, DW ALLABEN, WT TI SUBCHRONIC STUDIES OF PYRILAMINE IN FISCHER 344 RATS SO JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; METHAPYRILENE HYDROCHLORIDE; ANTIHISTAMINES; THENYLDIAMINE; ASSAY AB This study was designed to determine the subchronic effects of the antihistamine, pyrilamine maleate, and to establish dose levels for a 2-year chronic study. Six male and six female F344 rats received dietary pyrilamine concentrations of 0, 392, 783, 1563, 3122, or 6276 ppm (as the free base) for 14 days. Only weight gain suppression was noted, at 3122 and 6276 ppm, especially in males. When 12 male and 12 female F344 rats were fed pyrilamine for 90 days at 0, 750, 1500, 3000, 6000, or 12,000 ppm, weight gain was suppressed and organ/body weight ratios often were higher than in controls at 3000 ppm and above. Heart/brain and thymus/brain ratios were decreased at 3000 ppm and above in males and at 6000 or 12,000 ppm in females. All rats receiving 6000 or 12,000 ppm pyrilamine exhibited severe diffuse parenchymal cell cytomegaly in the parotid salivary glands with a dose-related decrease in severity and prevalence at lower concentrations. Hepatocellular vacuolization, present only in males, increased in severity with dose, starting at 750 ppm. The severity of liver fatty metamorphosis increased with dose at the three low doses but was less apparent and/or disappeared at 6000 and 12,000 ppm. It was concluded that 3000 ppm pyrilamine would not be life threatening to F344 rats in a chronic study. C1 NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. RP GREENMAN, DL (reprint author), NATL CTR TOXICOL RES,OFF SCI COORDINAT,JEFFERSON,AR 72079, USA. NR 17 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0730-0913 J9 J AM COLL TOXICOL JI J. Am. Coll. Toxicol. PD APR PY 1993 VL 12 IS 2 BP 175 EP 183 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LC608 UT WOS:A1993LC60800008 ER PT J AU ZIMMER, JP LEWIS, SM MOYER, JL AF ZIMMER, JP LEWIS, SM MOYER, JL TI COMPARISON OF GAVAGE, WATER BOTTLE, AND A HIGH-MOISTURE DIET BOLUS AS DOSING METHODS FOR QUANTITATIVE D-XYLOSE ADMINISTRATION TO B6D2F1 (MUS-MUSCULUS) MICE SO LABORATORY ANIMALS LA English DT Article DE DOSING METHODS; HIGH-MOISTURE DIET; MEAL; GAVAGE; WATER BOTTLE; D-XYLOSE; XYLOSE TOLERANCE TEST ID ABSORPTION AB Gavage, water bottle, and diet incorporation are 3 dosing methods used orally to administer test compounds to rodents. These 3 methods were compared in mice to determine which represented the most quantitative delivery system. For dietary incorporation, a high-moisture bolus form of NIH-31 rodent meal was developed using hydroxypropyl methylcellulose as an autoclave-stable binding agent. A high-moisture bolus was selected to increase the acceptability of the dosed diet and to promote quantitative consumption through reduced wastage. The test compound used was D-xylose, a pentose sugar that may be quantitatively detected, colorimetrically, in urine following oral dosing. Six male and 6 female B6D2F1 mice were placed in metabolism cages and dosed with a known quantity of D-xylose by each of the 3 methods. Urine was collected before and after each method of administration and analysed for total D-xylose; the per cent recovery was based upon the amount of D-xylose consumed. Quantitative consumption was apparently greatest for water bottle dosing with an average recovery of 56.0% of the original D-xylose dose. High-moisture bolus incorporation ranked second with 50.0% D-xylose recovery, and gavage was third with 41.0% D-xylose recovery. C1 BIONET CORP,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. CORNELL UNIV,DIV NUTR SCI,ITHACA,NY 14850. BIONET CORP,NASA,KENNEDY SPACE CTR,FL 32899. NR 19 TC 5 Z9 5 U1 0 U2 0 PU ROYAL SOC MEDICINE SERVICES LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0023-6772 J9 LAB ANIM JI Lab. Anim. PD APR PY 1993 VL 27 IS 2 BP 164 EP 170 DI 10.1258/002367793780810423 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA KV919 UT WOS:A1993KV91900011 PM 8501899 ER PT J AU JOSHI, M DWYER, DM NAKHASI, HL AF JOSHI, M DWYER, DM NAKHASI, HL TI CLONING AND CHARACTERIZATION OF DIFFERENTIALLY EXPRESSED GENES FROM INVITRO-GROWN AMASTIGOTES OF LEISHMANIA-DONOVANI SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE LEISHMANIA-DONOVANI; INVITRO AMASTIGOTE; DIFFERENTIAL GENE REGULATION; RIBOSOMAL PROTEIN; STRESS-INDUCIBLE PROTEIN; IMMUNOREACTIVITY; VISCERAL LEISHMANIASIS ID RIBOSOMAL PROTEIN-S11; SURFACE GLYCOPROTEIN; NUCLEOTIDE-SEQUENCE; PROMASTIGOTES; STAGE; MACROPHAGES; MEXICANA; CULTURE AB Leishmanial parasites routinely undergo cyclic differentiation from promastigotes to amastigotes during their life cycle. This process involves both morphological and macromolecular changes. To study such changes, we used a axenic culture system which permits the continuous generation and cycling of Leishmania donovani from promastigotes to 'amastigotes' in vitro. cDNA libraries were constructed from poly(A)+ RNA isolated from both the pro- and amastigote forms. Using differential cDNA hybridization techniques, 3 unique cDNAs clones (P17, A41 and A45) were isolated from the amastigote library. To assess whether these clones were differentially expressed by the pro-or 'amastigotes' forms, they were hybridized to RNA isolated from each of these parasite forms in Northern and slot-blots. Results of these analyses showed that 'amastigotes' had approx. 2-fold higher levels of the A41 and A45 RNAs compared to the promastigotes. Conversely, promastigotes showed approx. 2-fold higher levels of the P17 RNA than 'amastigotes'. Nucleotide sequence analysis and comparison with those in Gene bank, revealed that the 3 cDNAs represent unique leishmanial genes. Comparison of the deduced amino acid sequences revealed that: P17 open reading frame (ORF) had significant similarity with a soybean ribosomal protein S11; A41 ORF with a Bacillus subtilis spore germination gene (gerC) and A45 ORF with yeast stress-inducible protein (STI1). It is of interest to note that. of the 3 cDNAs identified, the A45-encoded protein was recognized by sera from patients with clinically active visceral leishmaniasis and was encoded by a single copy gene. C1 CBER,FOOD & DRUG ADM,DIV BIOCHEM & BIOPHYS,BIOCHEM LAB,BLDG 29,RM 107,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 30 TC 90 Z9 92 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD APR PY 1993 VL 58 IS 2 BP 345 EP 354 DI 10.1016/0166-6851(93)90057-5 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA KU715 UT WOS:A1993KU71500017 PM 8479459 ER PT J AU SCHREIBERAGUS, N TORRES, R HORNER, J LAU, A JAMRICH, M DEPINHO, RA AF SCHREIBERAGUS, N TORRES, R HORNER, J LAU, A JAMRICH, M DEPINHO, RA TI COMPARATIVE-ANALYSIS OF THE EXPRESSION AND ONCOGENIC ACTIVITIES OF XENOPUS C-MYC, N-MYC, AND L-MYC HOMOLOGS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAJOR DEVELOPMENTAL TRANSITION; PROTO-ONCOGENE; MESSENGER-RNA; NEOPLASTIC TRANSFORMATION; DIFFERENTIAL EXPRESSION; EMBRYO FIBROBLASTS; SEQUENCE-ANALYSIS; CELL-DIVISION; MOUSE EMBRYOS; DNA-BINDING AB A polymerase chain reaction-based cloning strategy allowed for the isolation of two distinct Xenopus L-myc genes, as well as previously isolated xc- and xN-myc genes, thus demonstrating that these three well-defined members of the mammalian myc gene family are present in lower vertebrates as well. Comparison of the Xenopus and mammalian Myc families revealed a high degree of structural relatedness at the gene and protein levels; this homology was consistent with the ability of the xc-myc1 and xN-myc1 genes to function as oncogenes in primary mammalian cells. In contrast, the xL-myc1 gene was found to be incapable of transforming rat embryo fibroblast cells, and this inactivity may relate to localized but significant differences in its putative transactivation domain. Analysis of xc-, xN-, and xL-myc gene expression demonstrated that (i) all three genes were highly expressed during oogenesis and their transcripts accumulated as abundant maternal mRNAs, (ii) each gene exhibited a distinctive pattern of expression during embryogenesis and in adult tissues, and (iii) the xL-myc1 and xL-myc2 genes were coordinately expressed in the maternal and zygotic genomes. The markedly high expression of the Xenopus myc gene family in differentiated tissues, such as the central nervous system and kidney, contrasts sharply with the low levels observed in mammalian adult tissues. These differences may reflect unique functions of the Myc family proteins in processes specific to amphibians, such as tissue regeneration. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10461. US FDA,CTR BIOL EVALUAT & RES,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA09173-14]; NEI NIH HHS [R01 EY09300-01]; NIGMS NIH HHS [T32 GM07128] NR 57 TC 30 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1993 VL 13 IS 4 BP 2456 EP 2468 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KT913 UT WOS:A1993KT91300047 PM 8455622 ER PT J AU FENG, P AF FENG, P TI IDENTIFICATION OF ESCHERICHIA-COLI SEROTYPE O157-H7 BY DNA PROBE SPECIFIC FOR AN ALLELE OF UID A-GENE SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE DNA PROBE; ESCHERICHIA-COLI; UID A-GENE ID HEMORRHAGIC COLITIS RP FENG, P (reprint author), US FDA,DIV MICROBIOL STUDIES,HFS-516,WASHINGTON,DC 20204, USA. NR 22 TC 51 Z9 52 U1 1 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD APR PY 1993 VL 7 IS 2 BP 151 EP 154 DI 10.1006/mcpr.1993.1021 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA LB940 UT WOS:A1993LB94000010 PM 8321253 ER PT J AU MATTIA, CJ ALI, SF BONDY, SC AF MATTIA, CJ ALI, SF BONDY, SC TI TOLUENE-INDUCED OXIDATIVE STRESS IN SEVERAL BRAIN-REGIONS AND OTHER ORGANS SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE ORGANIC SOLVENT; NEUROTOXICITY; TOLUENE; REACTIVE OXYGEN SPECIES; CENTRAL NERVOUS SYSTEM ID MEMBRANE FLUIDITY; PHOSPHOLIPID METHYLATION; RAT; CEREBELLAR; EXPOSURE; SYNAPTOSOMES; TOXICITY; BENZENE; SUPEROXIDE; METABOLISM AB The in vivo dose-response relationship between toluene and reactive oxygen species (ROS) formation in rat brain, liver, kidney, and lung, and the time-course of these effects has been characterized. The rate of oxygen radical formation was measured using the probe 2',7'-dichlorofluorescin diacetate. In vivo exposure to various doses of toluene (0.5, 1.0, and 1.5 g/kg ip) elicited a dose-dependent elevation of ROS generation within crude mitochondrial fractions obtained from rat lung and kidney, and within crude synaptosomal fractions from cerebellum. ROS formation in crude mitochondrial fractions from liver, and crude synaptosomal fractions from striatum and hippocampus, reached a maximum value at relatively low doses of toluene. Of the brain regions, the hippocampus had the highest induced levels of ROS. In vivo exposure to a single dose of toluene (1.5 g/kg ip), revealed that toluene-induced ROS reached a peak within 2 h, which correlated directly with measured toluene blood levels. This elevated oxidative activity was maintained throughout the next 24 h, even though blood values of toluene decreased to negligible amounts. These results demonstrate that exposure to toluene results in broad systemic elevation in the normal rate of oxygen radical generation, with such effects persisting in the tissues despite a rapid decline in toluene blood levels. Acute exposure to toluene may lead to extended ROS-related changes, and this may account for some of the clinical observations made in chronic toluene abusers. C1 UNIV CALIF IRVINE,DEPT COMMUNITY & ENVIRONM MED,FRF BLDG,IRVINE,CA 92717. NATL CTR TOXICOL RES,DIV REPROD & DEV TOXICOL,JEFFERSON,AR 72079. FU NIAAA NIH HHS [AA8281]; NIEHS NIH HHS [ES04071] NR 50 TC 62 Z9 66 U1 2 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD APR PY 1993 VL 18 IS 3 BP 313 EP 328 PG 16 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA KZ118 UT WOS:A1993KZ11800009 PM 8507307 ER PT J AU LINDLER, LE TALL, BD AF LINDLER, LE TALL, BD TI YERSINIA-PESTIS PH-6 ANTIGEN FORMS FIMBRIAE AND IS INDUCED BY INTRACELLULAR ASSOCIATION WITH MACROPHAGES SO MOLECULAR MICROBIOLOGY LA English DT Article ID UROPATHOGENIC ESCHERICHIA-COLI; MOUSE PERITONEAL-MACROPHAGES; CHAPERONE PROTEIN-PAPD; NUCLEOTIDE-SEQUENCE; VIRULENCE DETERMINANTS; K99 FIMBRIAE; PLASMID; PILUS; BIOSYNTHESIS; BINDING AB Ability to express pH 6 antigen (Ag) is necessary for full virulence of Yersinia pestis; however, the function of the Ag in pathogenesis remains unclear. We determined the nucleotide sequence of a 4232 bp region of Y. pestis DNA which encoded the pH 6 Ag structural gene (psaA) and accessory loci necessary for Ag synthesis. Protein sequences encoded by the Y. pestis DNA were similar to accessory proteins which function in the biosynthesis of Escherichia coli fimbriae Pap, K88, K99 and CS3 as well as the molecular chaperone for the Y. pestis capsule protein. Electron microscopy and immunogold labelling studies revealed that pH 6 Ag expressing E. coli or Yersinia produced flexible 'fibrillar' organelles composed of individual linear strands, multiple strand bundles or wiry aggregates of PsaA. Y. pestis associated with the murine macrophage-like cell line, RAW264.7, expressed pH 6 Ag in an intracellular acidification-dependent manner. Together with an earlier study showing that a Y. pestis psaA mutant was reduced in virulence, these results demonstrate that the expression of fimbriae which are induced in host macrophages is involved in plague pathogenesis. C1 US FDA,DIV MICROBIOL,WASHINGTON,DC 20204. RP LINDLER, LE (reprint author), WALTER REED ARMY INST RES,DEPT IMMUNOL,DIV COMMUNICABLE DIS & IMMUNOL,WASHINGTON,DC 20307, USA. OI Tall, Ben/0000-0003-0399-3629 NR 55 TC 107 Z9 113 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 1993 VL 8 IS 2 BP 311 EP 324 DI 10.1111/j.1365-2958.1993.tb01575.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA KY689 UT WOS:A1993KY68900012 PM 8100346 ER PT J AU SHADDOCK, JG FEUERS, RJ CHOU, MW CASCIANO, DA AF SHADDOCK, JG FEUERS, RJ CHOU, MW CASCIANO, DA TI EVIDENCE THAT DNA-REPAIR MAY NOT BE MODIFIED BY AGE OR CHRONIC CALORIC RESTRICTION SO MUTATION RESEARCH LA English DT Article DE AROCLOR; ENZYME INDUCTION; DNA REPAIR; RAT HEPATOCYTES; METABOLISM; AGING; CALORIC RESTRICTION ID DRUG-METABOLIZING-ENZYMES; DEPENDENT MONOOXYGENASE SYSTEM; FISCHER-344 RAT; DIETARY RESTRICTION; FOOD RESTRICTION; CYTOCHROME-P-450; ACTIVATION; SEX AB Pretreatment of animals with mixed-function oxidase inducers has been shown to increase the metabolic activation capacity of isolated hepatocytes resulting in an apparent increase in DNA repair. We recently reported decreases in chemically-induced DNA repair, measured as unscheduled DNA synthesis (UDS), in hepatocyte cultures isolated from aging ad libitum (AL) and caloric restricted (CR) diet-fed animals. In the present study, we evaluated the effects of pretreatment with Aroclor 1254 (ARO) on the genotoxicity of 4 carcinogens, from different chemical classes, in primary hepatocytes isolated from male Fischer 344 rats. ARO-induced old AL- and CR-derived cultures, treated with 2-acetylaminofluorene (2-AAF), aflatoxin B1 (AFB1), 7,12-dimethylbenz[a]anthracene (DMBA), and dimethylnitrosamine (DMN), exhibited significant induction-related increases in DNA repair in comparison to uninduced old AL and CR animals. These data indicate that the constitutive levels of specific cytochrome P450 decline with age and chronic caloric restriction, while the ability to respond to exogenous inducers is retained, and suggest that DNA repair may not be modified with age or diet restriction. C1 NATL CTR TOXICOL RES,DIV COMPARAT TOXICOL,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT ANAT,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. RP SHADDOCK, JG (reprint author), NATL CTR TOXICOL RES,DIV GENET TOXICOL,HFT 120,NCTR DR,JEFFERSON,AR 72079, USA. NR 24 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD APR PY 1993 VL 301 IS 4 BP 261 EP 266 DI 10.1016/0165-7992(93)90067-6 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA KU561 UT WOS:A1993KU56100009 PM 7680761 ER PT J AU HWANG, JJ HSIA, MTS JIRTLE, RL AF HWANG, JJ HSIA, MTS JIRTLE, RL TI INDUCTION OF SISTER CHROMATID EXCHANGE AND MICRONUCLEI IN PRIMARY CULTURES OF RAT AND HUMAN HEPATOCYTES BY THE PEROXISOME PROLIFERATOR, WY-14,643 SO MUTATION RESEARCH LA English DT Article DE HEPATOCYTES; SISTER-CHROMATID EXCHANGE; MICRONUCLEI; PEROXISOME PROLIFERATOR; WY-14,643 ID UNSCHEDULED DNA-SYNTHESIS; LONG-TERM EXPOSURE; LIVER DNA; DI(2-ETHYLHEXYL)PHTHALATE DEHP; HEPATIC TUMORIGENESIS; GENOTOXIC ACTIVITY; BETA-OXIDATION; INVITRO; CLOFIBRATE; PHTHALATE AB The ability of peroxisome proliferators to induce hepatocellular carcinomas in rodents has been known since the mid 1970's, but the mechanism of tumor formation is still poorly understood. In this study, we have used primary cultures of both rat and human hepatocytes to address the question of whether the peroxisome proliferator, [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14,643), causes genotoxic damage in hepatocytes as measured by sister chromatid exchange (SCE), micronuclei formation, and chromosomal aberrations. We have found that in rat hepatocytes the number of SCEs per chromosome increased in a dose-dependent manner from a background level of 0.7 to a maximum of 1.1 in cells exposed for 48 h to 100 muM of Wy-14,643. In contrast, no increase in SCE frequency was observed in rat hepatocytes exposed to Wy-14,643 for 3 h. A dose-dependent increase in micronuclei formation was also seen in the 48 h but not in the 3 h cultures. The maximum frequency of micronuclei formation after a 48 h exposure occurred at 20 muM Wy-14,643 and was 2.3 times that for control cells. At this concentration of Wy-14,643, the frequency of chromosomal aberrations was increased by more than 10-fold. A 48 h exposure to Wy-14,643 also significantly increased micronuclei formation in human hepatocytes, but it was less effective than in rat hepatocytes. To investigate the potential role of peroxisome proliferation in these genotoxic responses, we measured the activities of palmitoyl-CoA beta-oxidase in hepatocytes exposed for 48 h to Wy-14,643. A dose-dependent increase in palmitoyl-CoA beta-oxidase activity was observed in rat hepatocytes, but not in human hepatocytes. The SCE frequency in rat hepatocytes correlated well with the degree of peroxisome proliferation, however, the increased formation of micronuclei in both rat and human hepatocytes occurred by a mechanism that appeared to be independent of peroxisome induction. In summary, these results demonstrate that the peroxisome proliferator, Wy-14,643, causes genotoxic damage in primary cultures of both rat and human hepatocytes. C1 DUKE UNIV,MED CTR,DEPT RADIAT ONCOL,POB 3433,DURHAM,NC 27710. US FDA,MOLEC TOXICOL BRANCH,LAUREL,MD 20708. NATL YANG MING MED COLL,SCH MED TECHNOL,TAIPEI,TAIWAN. FU NCI NIH HHS [CA40172, CA25951] NR 52 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD APR PY 1993 VL 286 IS 2 BP 123 EP 133 DI 10.1016/0027-5107(93)90176-G PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA KU021 UT WOS:A1993KU02100002 PM 7681523 ER PT J AU MATSON, DO BYINGTON, C CANFIELD, M ALBRECHT, P FEIGIN, RD AF MATSON, DO BYINGTON, C CANFIELD, M ALBRECHT, P FEIGIN, RD TI INVESTIGATION OF A MEASLES OUTBREAK IN A FULLY VACCINATED SCHOOL POPULATION INCLUDING SERUM STUDIES BEFORE AND AFTER REVACCINATION SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE MEASLES; ANTIBODY; PROTECTION; REVACCINATION ID RISK-FACTORS; TRANSMISSION; FAILURE AB A measles outbreak in early 1989 among approximately 4200 students at a high school and two intermediate schools in suburban Houston, TX, was investigated to evaluate reasons for vaccine failure and to predict the efficacy of a booster dose of measles vaccine. Seventy-seven cases occurred (71 at the high school, 6 at intermediate schools; attack rate, 3.2 and 0.3%, respectively). Vaccination in the first year of life an 13 to 14 years since last vaccination were independent risk factors for being a case. Forty-three (18%) of 239 sera collected from students just before revaccination during the outbreak were negative by enzyme immunoassay; a neutralization assay confirmed these 43 lacked antibody predicting protection against measles infection. Of 43 enzyme immunoassay-negative students 24 gave another blood sample 9 to 10 months after revaccination. Revaccination appeared to reduce the portion of all students with neutralization titers predicting susceptibility to measles illness with rash from 7.9% to 3.0% and left the portion predicted to be susceptible to illness without rash unchanged (45%). C1 BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. HARRIS CTY HLTH DEPT,EPIDEMIOL SECT,HOUSTON,TX. US FDA,CTR BIOL RES & EVALUAT,BETHESDA,MD 20014. RP MATSON, DO (reprint author), BAYLOR COLL MED,DEPT PEDIAT,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. NR 22 TC 23 Z9 24 U1 0 U2 4 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 APR PY 1993 VL 12 IS 4 BP 292 EP 299 DI 10.1097/00006454-199304000-00007 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA KW848 UT WOS:A1993KW84800007 PM 8483623 ER PT J AU WEISS, AA JOHNSON, FD BURNS, DL AF WEISS, AA JOHNSON, FD BURNS, DL TI MOLECULAR CHARACTERIZATION OF AN OPERON REQUIRED FOR PERTUSSIS TOXIN SECRETION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; ISLET-ACTIVATING PROTEIN; BORDETELLA-PERTUSSIS; AGROBACTERIUM-TUMEFACIENS; VIRB OPERON; GENE; CLONING; ORGANIZATION; ANTIBODIES; INFECTION AB Mutants of Bordetella pertussis which are defective in secretion of pertussis toxin were isolated and characterized. The region of the B. pertussis chromosome identified by mutagenesis as playing a role in transport of pertussis toxin was sequenced. Analysis of this region revealed eight open reading frames, seven of which predict a protein exhibiting homology with one of the VirB proteins of Agrobacterium tumefaciens, which are involved in the transport of the T-DNA molecule across bacterial and plant membranes. Thus a set of accessory proteins are most likely involved in the secretion of pertussis toxin, and these proteins appear to be members of a family of proteins involved in the secretion of macromolecules from bacteria. C1 CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,DEPT MICROBIOL & IMMUNOL,RICHMOND,VA 23298. FU NIAID NIH HHS [AI23695] NR 24 TC 223 Z9 240 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 1993 VL 90 IS 7 BP 2970 EP 2974 DI 10.1073/pnas.90.7.2970 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KV975 UT WOS:A1993KV97500086 PM 8464913 ER PT J AU ELLWOOD, KC CHATZIDAKIS, C FAILLA, ML AF ELLWOOD, KC CHATZIDAKIS, C FAILLA, ML TI FRUCTOSE UTILIZATION BY THE HUMAN INTESTINAL EPITHELIAL-CELL LINE, CACO-2 SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID BRUSH-BORDER; TRANSPORT; COLON; GLUCOSE; DIFFERENTIATION; CULTURE; SYSTEM; RAT; GUT AB The potential use of Caco-2 cells as a model for the study of fructose metabolism and transport in the intestine was evaluated, since this human cell line exhibits many of the anatomical and biochemical characteristics of mature enterocytes. Pre- and postconfluent cultures converted [C-14]fructose to CO2, lipid, and glycogen. Apparent utilization of [C-14]fructose was less than that of [C-14]glucose. This difference was due in part to the more rapid uptake of glucose from medium as compared with fructose. Addition of glucose, galactose, and mannose to medium markedly decreased the metabolism, while slightly inhibiting the uptake, of [C-14]fructose. These data demonstrate that fructose can serve as a carbon and energy source for Caco-2 cells, and that common dietary monosaccharides affect the efficiency of fructose metabolism. C1 UNIV N CAROLINA,DEPT FOOD NUTR & FOOD SERV MANAGEMENT,GREENSBORO,NC 27412. USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE,MD 20705. US FDA,DIV NUTR,LAUREL,MD 20708. NR 30 TC 18 Z9 18 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD APR PY 1993 VL 202 IS 4 BP 440 EP 446 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KU637 UT WOS:A1993KU63700008 PM 8456108 ER PT J AU VENABLE, RM BROOKS, BR CARSON, FW AF VENABLE, RM BROOKS, BR CARSON, FW TI THEORETICAL-STUDIES OF RELAXATION OF A MONOMERIC SUBUNIT OF HIV-1 PROTEASE IN WATER USING MOLECULAR-DYNAMICS SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE AIDS; ENERGY MINIMIZATION; ENZYME INHIBITION; MOLECULAR MODELING; PROTEIN CONFORMATION; CROSS-CORRELATION MAP ID IMMUNODEFICIENCY-VIRUS PROTEASE; 3-DIMENSIONAL STRUCTURE; RETROVIRAL PROTEASES; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; TYPE-1 PROTEASE; RESOLUTION; INHIBITOR; COMPLEX; AIDS AB The dynamic behavior of one 99-residue subunit of the dimeric aspartyl protease of HIV-1 was studied in a 160 psec molecular dynamics simulation at 300 K in water. The crystal structure of one of the identical subunits of the dimer was the starting point, with the aqueous phase modeled by 4,331 explicit waters in a restrained spherical droplet. Analysis of the simulations showed that the monomer displayed considerable flexibility in the interfacial portions of the flap (the region which folds over the substrate), the N- and C-termini, and, to a lesser extent, the active site. The flap undergoes significant motion as an independent rigid finger, but without the cantilever previously reported in a simulation of the dimer. The N-terminus displayed the greatest fluctuational disorder whereas the C-terminus exhibited the greatest root mean square movement from the crystal structure. The central core of the monomer had a heavy-atom root mean square deviation from the initial structure of about 3.0 angstrom during the latter half of the simulation. Although this is larger than the 1.6 A found for comparable simulations of typical globular proteins, the general features of the tertiary structure were preserved over the course of the simulation. Overall, these results indicate that the relaxed structure obtained in these simulations may provide a better model for the tertiary structure of the solvated HIV-1 protease monomer than the subunit conformation seen in the X-ray crystallographic structure of the dimer. Except in the flap region, the design of compounds intended to interfere with dimerization should take this relaxation and the flexibility of the solvated monomer, especially at the termini, into account. C1 NIH,DIV COMP RES & TECHNOL,MOLEC GRAPH & SIMULAT LAB,BETHESDA,MD 20892. AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. RP VENABLE, RM (reprint author), US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [BBCA 1 R15 AI26307-01] NR 46 TC 21 Z9 21 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 0887-3585 J9 PROTEINS JI Proteins PD APR PY 1993 VL 15 IS 4 BP 374 EP 384 DI 10.1002/prot.340150405 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KT967 UT WOS:A1993KT96700004 PM 8460108 ER PT J AU SCHEVING, LE SCHEVING, LA FEUERS, RJ TSAI, TH COPE, FO AF SCHEVING, LE SCHEVING, LA FEUERS, RJ TSAI, TH COPE, FO TI CHRONOBIOLOGY AS IT RELATES TO TOXICOLOGY, PHARMACOLOGY, AND CHEMOTHERAPY SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID LEUKEMIC MICE; CYCLOPHOSPHAMIDE; MEDICINE; BIOLOGY; CANCER; TIME C1 JOHN L MCCLELLAN MEM VET ADM MED CTR,LITTLE ROCK,AR 72205. VANDERBILT UNIV,MED CTR,SCH MED,DEPT PATHOL,NASHVILLE,TN 37232. US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. ROSS LABS,COLUMBUS,OH. RP SCHEVING, LE (reprint author), UNIV ARKANSAS MED SCI HOSP,DEPT ANAT,LITTLE ROCK,AR 72205, USA. NR 37 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 1993 VL 17 IS 2 BP 209 EP 218 DI 10.1006/rtph.1993.1018 PN 1 PG 10 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA KY664 UT WOS:A1993KY66400007 PM 8484028 ER PT J AU GAYLOR, DW CHEN, JJ SHEEHAN, DM AF GAYLOR, DW CHEN, JJ SHEEHAN, DM TI UNCERTAINTY IN CANCER RISK ESTIMATES SO RISK ANALYSIS LA English DT Article DE CANCER RISK ESTIMATION; UNCERTAINTY ID CARCINOGENIC POTENCY DATABASE; BIOASSAYS; CHEMICALS; EXPOSURES; MODEL AB Several existing databases compiled by Gold et al. (1-3) for carcinogenesis bioassays are examined to obtain estimates of the reproducibility of cancer rates across experiments, strains, and rodent species. A measure of carcinogenic potency is given by the TD50 (daily dose that causes a tumor type in 50% of the exposed animals that otherwise would not develop the tumor in a standard lifetime). The lognormal distribution can be used to model the uncertainty of the estimates of potency (TD50) and the ratio of TD50's between two species. For near-replicate bioassays, approximately 95% of the TD50's are estimated to be within a factor of 4 of the mean. Between strains, about 95% of the TD50's are estimated to be within a factor of 11 of their mean, and the pure genetic component of variability is accounted for by a factor of 6.8. Between rats and mice, about 95% of the TD50's are estimated to be within a factor of 32 of the mean, while between humans and experimental animals the factor is 1 10 for 20 chemicals reported by Allen et al.(4) The common practice of basing cancer risk estimates on the most sensitive rodent species-strain-sex and using interspecies dose scaling based on body surface area appears to overestimate cancer rates for these 20 human carcinogens by about one order of magnitude on the average. Hence, for chemicals where the dose-response is nearly linear below experimental doses, cancer risk estimates based on animal data are not necessarily conservative and may range from a factor of 10 too low for human carcinogens up to a factor of 1000 too high for approximately 95% of the chemicals tested to date. These limits may need to be modified for specific chemicals where additional mechanistic or pharmacokinetic information may suggest alterations or where particularly sensitive subpopulations may be exposed. Supralinearity could lead to anticonservative estimates of cancer risk. Underestimating cancer risk by a specific factor has a much larger impact on the actual number of cancer cases than overestimates of smaller risks by the same factor. This paper does not address the uncertainties in high to low dose extrapolation. If the dose-response is sufficiently nonlinear at low doses to produce cancer risks near zero, then low-dose risk estimates based on linear extrapolation are likely to overestimate risk and the limits of uncertainty cannot be established. RP GAYLOR, DW (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 17 TC 30 Z9 30 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD APR PY 1993 VL 13 IS 2 BP 149 EP 154 DI 10.1111/j.1539-6924.1993.tb01064.x PG 6 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA KY737 UT WOS:A1993KY73700008 PM 8502788 ER PT J AU KODELL, RL WEST, RW AF KODELL, RL WEST, RW TI UPPER CONFIDENCE-LIMITS ON EXCESS RISK FOR QUANTITATIVE RESPONSES SO RISK ANALYSIS LA English DT Article DE ADDITIONAL RISK; BENCHMARK DOSE; LIKELIHOOD RATIO; NONCENTRAL T AB The definition and observation of clear-cut adverse health effects for continuous (quantitative) responses, such as altered body weights or organ weights, are difficult propositions. Thus, methods of risk assessment commonly used for binary (quantal) toxic responses such as cancer are not directly applicable. In this paper, two methods for calculating upper confidence limits on excess risk for quantitative toxic effects are proposed, based on a particular definition of an adverse quantitative response. The methods are illustrated with data from a dose-response study, and their performance is evaluated with a Monte Carlo simulation study. RP KODELL, RL (reprint author), NATL CTR TOXICOL RES,HFT 20,NCTR DR,JEFFERSON,AR 72079, USA. NR 18 TC 74 Z9 74 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD APR PY 1993 VL 13 IS 2 BP 177 EP 182 DI 10.1111/j.1539-6924.1993.tb01067.x PG 6 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA KY737 UT WOS:A1993KY73700011 PM 8502790 ER PT J AU GAYLOR, DW CHEN, JJ AF GAYLOR, DW CHEN, JJ TI DOSE-RESPONSE MODELS FOR DEVELOPMENTAL MALFORMATIONS SO TERATOLOGY LA English DT Article ID INDUCED CLEFT-PALATE; PRENATAL DEVELOPMENT; MICE; TOXICITY; RATS; TERATOGENICITY; MOUSE; CYCLOPHOSPHAMIDE; CORTICOSTERONE; ACID AB An empirical dose-response model can generally be found for bioassay data, which provides a mathematical relationship between the incidence of a developmental malformation and dose of a toxicant in the experimental dose range. If biological principles and data can be used in the formulation of the dose-response model, the estimation of the incidence of malformations outside of the experimental dose range may be improved. In this paper, exponential growth of morphological structures in rodents during gestation is assumed. Further, it is assumed that some structural malformations are the result of reduced or delayed growth and the incidence of structurally normal fetuses is proportional to fetal weight raised to a power. When the exponential growth rate constant is reduced by dose raised to a power, a Weibull dose-response function is obtained. When the exponential growth rate constant is modeled by a polynomial function of dose, a polynomial-exponential dose-response model is obtained. The Weibull and the polynomial-exponential model, restricted to degrees from one up to the number of dosed groups, were fit to a database of bioassay data assembled from Teratology Vol. 1 (1968) to Vol. 42 (1990). In general the two models gave similar results and often gave exactly the same fit. The linear term appeared in the polynomial-exponential model in about one-fourth of the cases and was not related to the background incidence. RP GAYLOR, DW (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. NR 31 TC 10 Z9 10 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 APR PY 1993 VL 47 IS 4 BP 291 EP 297 DI 10.1002/tera.1420470406 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA KW876 UT WOS:A1993KW87600005 PM 8322223 ER PT J AU ROTTEM, S BARILE, MF AF ROTTEM, S BARILE, MF TI BEWARE OF MYCOPLASMAS SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID TUMOR NECROSIS FACTOR; CELL-CULTURE MYCOPLASMAS; TISSUE-CULTURES; MAMMALIAN-CELLS; RIBOSOMAL-RNA; FACTOR-ALPHA; CONTAMINATION; INFECTION; VIRUS; INDUCTION AB Mycoplasma infection of cell cultures is widespread and has major detrimental effects on cellular physiology and metabolism. Since cell culture is used extensively, both in research and in industrial production processes, questions of primary concern arise, such as: how can mycoplasma contamination be detected; what are the effects of such contamination on cellular functions; what methods are available for eliminating contamination? C1 US FDA,CTR BIOL EVALUAT & RES,MYCOPLASMA LAB,BETHESDA,MD 20892. RP ROTTEM, S (reprint author), HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MEMBRANE & ULTRASTRUCT RES,POB 1172,IL-91010 JERUSALEM,ISRAEL. NR 75 TC 77 Z9 81 U1 1 U2 8 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 APR PY 1993 VL 11 IS 4 BP 143 EP 151 DI 10.1016/0167-7799(93)90089-R PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA LC856 UT WOS:A1993LC85600007 PM 7763647 ER PT J AU BERKOWER, I MURPHY, D AF BERKOWER, I MURPHY, D TI ENZYMATIC LABELING OF BIOLOGICALLY-ACTIVE ENVELOPE GLYCOPROTEIN-GP120 OF HIV-1 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZING EPITOPE; GP120; TYPE-1; BINDING; REGION; INFECTION; CELLS RP BERKOWER, I (reprint author), US FDA,CTR BIOL,DIV ALLERGEN & PARASITOL,IMMUNE RESPONSE LAB,NIH CAMPUS,BETHESDA,MD 20892, USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 31 PY 1993 VL 191 IS 3 BP 1055 EP 1065 DI 10.1006/bbrc.1993.1324 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KV405 UT WOS:A1993KV40500042 PM 8466484 ER PT J AU HEREDIA, A SORIANO, V EPSTEIN, JS HEWLETT, IK AF HEREDIA, A SORIANO, V EPSTEIN, JS HEWLETT, IK TI ENHANCED DIAGNOSTIC EFFICIENCY OF THE POLYMERASE CHAIN-REACTION (PCR) BY COAMPLIFICATION OF MULTIPLE REGIONS OF HIV-1 AND HIV-2, UDAYKUMAR SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 CBER,FDA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 29 PY 1993 SU 17E BP 19 EP 19 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KX965 UT WOS:A1993KX96500060 ER PT J AU JOSHI, B EPSTEIN, J RIORDAN, G NORCROSS, M HEWLETT, IK AF JOSHI, B EPSTEIN, J RIORDAN, G NORCROSS, M HEWLETT, IK TI ENHANCEMENT OF HIV-1 REPLICATION BY CIGARETTE-SMOKE CONSTITUENTS - INVOLVEMENT OF NF-KB, PK-C AND TNF-ALPHA SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 29 PY 1993 SU 17E BP 31 EP 31 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KX965 UT WOS:A1993KX96500107 ER PT J AU POFFENBERGER, KL RIORDAN, G LEE, S EPSTEIN, J HEWLETT, I AF POFFENBERGER, KL RIORDAN, G LEE, S EPSTEIN, J HEWLETT, I TI PERSISTENT HIV-1 (MN) INFECTION OF MAMMARY EPITHELIAL-CELLS INVITRO SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 29 PY 1993 SU 17E BP 36 EP 36 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KX965 UT WOS:A1993KX96500126 ER PT J AU MCLAUGHLIN, MA DIACHENKO, GW AF MCLAUGHLIN, MA DIACHENKO, GW TI EFFECTS OF ELEVATED-TEMPERATURES ON THE MOLECULAR-WEIGHT OF FOOD-GRADE CARRAGEENAN SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 1993 VL 205 BP 12 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA KQ981 UT WOS:A1993KQ98100012 ER PT J AU HOLLINGWORTH, TA HUNGERFORD, JM BARNETT, JD TENGE, BJ WEKELL, MM AF HOLLINGWORTH, TA HUNGERFORD, JM BARNETT, JD TENGE, BJ WEKELL, MM TI TOTAL VOLATILE ACIDS - AN INDICATOR OF DECOMPOSITION IN HALIBUT AS DETERMINED BY FLOW-INJECTION ANALYSIS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,BOTHELL,WA 98041. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 1993 VL 205 BP 31 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA KQ981 UT WOS:A1993KQ98100031 ER PT J AU UENG, TH CHOU, MW AF UENG, TH CHOU, MW TI COMPARATIVE METABOLISM OF BENZO[A]PYRENE AND 7-CHLOROBENZO[A]PYRENE BY FISH AND RAT-LIVER MICROSOMES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL TAIWAN UNIV,TAIPEI,TAIWAN. NATL CTR TOXICOL RES,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 MAR 28 PY 1993 VL 205 BP 40 EP MEDI PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA KQ981 UT WOS:A1993KQ98103021 ER PT J AU TORTORELLO, ML GENDEL, SM AF TORTORELLO, ML GENDEL, SM TI MOLECULAR PROBE DETECTION OF BACTERIA IN 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 60501. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 1993 VL 205 BP 51 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA KQ981 UT WOS:A1993KQ98100051 ER PT J AU WITIAK, DT HERMAN, EH AF WITIAK, DT HERMAN, EH TI AMELIORATION OF ANTHRACYCLINE-INDUCED CARDIOTOXICITY BY ORGANIC-CHEMICALS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,DIV RES & TESTING,WASHINGTON,DC 20204. OHIO STATE UNIV,DIV MED CHEM,COLUMBUS,OH 43210. OHIO STATE UNIV,CTR COMPREHENS CANC,COLUMBUS,OH 43210. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 1993 VL 205 BP 51 EP CARB PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA KQ981 UT WOS:A1993KQ98100563 ER PT J AU HILL, WE AF HILL, WE TI GENE PROBES AND PCR - FOOD SAFETY APPLICATIONS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,SEAFOOD PROD RES CTR,BOTHELL,WA 98041. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 1993 VL 205 BP 53 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA KQ981 UT WOS:A1993KQ98100053 ER PT J AU CERNIGLIA, CE AF CERNIGLIA, CE TI OXIDATIVE BIODEGRADATION PATHWAYS OF PAHS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72070. NR 0 TC 0 Z9 0 U1 3 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 28 PY 1993 VL 205 BP 67 EP PETR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA KQ983 UT WOS:A1993KQ98300567 ER PT J AU PACKARD, BZ KOMORIYA, A AF PACKARD, BZ KOMORIYA, A TI A 36-KILODALTON TUMOR-DERIVED FACTOR WITH MYELOID IMMUNOMODULATORY ACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODIES; CANCER-THERAPY; IMMUNOLOGICAL SURVEILLANCE; CELLS; DEHYDROGENASE; CYTOKINES; DIFFERENTIATION; IMMUNOTHERAPY; CARCINOGENESIS; MACROPHAGES AB The conditioned medium from the epidermal carcinoma cell line A431 is shown to inhibit the growth of three human myeloid leukemic cell lines. We have purified to homogeneity from this conditioned medium a 36-kDa protein, as measured hy sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which inhibits [H-3]thymidine incorporation into the DNA and induces cell surface expression of CD11b, the alpha chain of the adhesion receptor MAC-1, on the human promyelocytic leukemic cell line HL-60. This factor was purified by sequential anion exchange, hydrophobic interaction, and gel permeation chromatography. Amino acid sequence analysis of two tryptic fragments of the purified material showed greater than 95% homology with sequences 179-194 and 319-328 of the M chain of human L-lactate dehydrogenase. Although the tetrameric L-lactate dehydrogenase alone exhibits no activities associated with the purified 36-kDa protein, brief acid treatment which has been shown to yield predominantly monomeric lactate dehydrogenase-M, results in about 50% of the maximal antiproliferative activity of that induced by this factor. The role of soluble factors of tumor origin in modulating myeloid function as part of an immunosurveillance network is discussed. RP PACKARD, BZ (reprint author), US FDA,CBER,DCB,BLDG 29A,ROOM 3B22,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 57 TC 7 Z9 7 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 MAR 25 PY 1993 VL 268 IS 9 BP 6356 EP 6363 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KT368 UT WOS:A1993KT36800043 PM 8454606 ER PT J AU DAVID, M ROMERO, G ZHANG, ZY DIXON, JE LARNER, AC AF DAVID, M ROMERO, G ZHANG, ZY DIXON, JE LARNER, AC TI INVITRO ACTIVATION OF THE TRANSCRIPTION FACTOR ISGF3 BY INTERFERON-ALPHA INVOLVES A MEMBRANE-ASSOCIATED TYROSINE PHOSPHATASE AND TYROSINE KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; SIGNAL TRANSDUCTION; RAPID ACTIVATION; BINDING; CELLS; ISOFORM; PP56LCK AB Interaction of interferon alpha (IFNalpha) with its cell surface receptor rapidly activates the formation of the transcription complex ISGF3, which subsequently translocates to the nucleus and stimulates the expression of a variety of early response genes. We have recently developed a cell-free system where IFNalpha can activate the formation of ISGF3 in vitro. This system has enabled us to demonstrate that the component of the ISGF3 transcription complex which is modified by IFNalpha treatment (ISGF3alpha) is membrane-associated and that its activation involves a protein kinase. Using a combination of specific tyrosine kinase and phosphatase inhibitors and monoclonal anti-phosphotyrosine antibodies we now are able to demonstrate that IFNalpha-activated transcription involves at least a two-step process where a membrane-associated tyrosine phosphatase and a tyrosine kinase lead to modification of ISGF3alpha and subsequent formation of the complete complex. Furthermore, formation of the ISGF3 complex is specifically disrupted by protein tyrosine phosphatase and can be reversibly dissociated by the phosphotyrosine analogue phenylphosphate. The latter observation suggested that SH2 and/or SH3 domains may be required for the stable formation of this transcription complex. C1 CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT BIOL CHEM,ANN ARBOR,MI 48109. UNIV PITTSBURGH,SCH MED,DEPT PHARMACOL,PITTSBURGH,PA 15261. FU PHS HHS [18824] NR 27 TC 92 Z9 92 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 MAR 25 PY 1993 VL 268 IS 9 BP 6593 EP 6599 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KT368 UT WOS:A1993KT36800075 PM 8454630 ER PT J AU LIN, LW LIU, TY AF LIN, LW LIU, TY TI ISOLATION AND CHARACTERIZATION OF C-REACTIVE PROTEIN (CRP) CDNA AND GENOMIC DNA FROM XENOPUS-LAEVIS - A SPECIES REPRESENTING AN INTERMEDIATE STAGE IN CRP EVOLUTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID-P-COMPONENT; BINDING-SITE; ACID; PURIFICATION; DETERMINANTS; SEQUENCE; SYSTEM AB C-reactive protein (CRP) is a prototypic acute phase protein in human and rabbit. Although it is structurally and functionally conserved from invertebrate to human, there are species-specific differences in patterns of expression and putative function. To further investigate the biological significance, regulation, and evolution of CRP, we isolated Xenopus CRP and subsequently derived and sequenced corresponding cDNA and the genomic clones. The structure and expression of Xenopus CRP were also compared to those of the other CRPs. Analyses of the amino acid sequence and the nucleotide sequence reveal that the mature Xenopus CRP is a 222-amino acid protein preceded by a 16-residue signal peptide. During development, Xenopus CRP is expressed, only when the liver appears, and therefore is not likely to play a role in early embryonic development. Compared to other species, Xenopus CRP is present at an intermediate low level of <1 mug/ml in the normal serum. Unlike human and rabbit CRP, Xenopus CRP is not induced by turpentine or heatshock treatment. The heatshock consensus sequence (Woo, P., Korenberg, J. R., and Whitehead, A. S. (1985) J. Biol. Chem. 265, 4136-4142) are not present in the Xenopus CRP gene. It is suggested that Xenopus CRP represents a transitional period in CRP evolution when host defenses switched from primitive innate immunity to a much more complex immune system. The constitutive functions of CRP gradually became less essential as the result of the development of a complex immune system. RP LIN, LW (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20892, USA. NR 51 TC 28 Z9 30 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 MAR 25 PY 1993 VL 268 IS 9 BP 6809 EP 6815 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KT368 UT WOS:A1993KT36800104 PM 8454653 ER PT J AU HONIG, PK WORTHAM, DC ZAMANI, K CONNER, DP MULLIN, JC CANTILENA, LR AF HONIG, PK WORTHAM, DC ZAMANI, K CONNER, DP MULLIN, JC CANTILENA, LR TI TERFENADINE-KETOCONAZOLE INTERACTION - PHARMACOKINETIC AND ELECTROCARDIOGRAPHIC CONSEQUENCES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ERYTHROMYCIN; METABOLITE AB Objective.-To examine prospectively the effects of ketoconazole on the pharmacokinetics and electrocardiographic repolarization pharmacodynamics (corrected QT intervals) of terfenadine in men and women. Design.-Prospective cohort study with each subject serving as his or her own control. Setting.-Outpatient cardiology clinic and inpatient telemetry unit for monitoring period. Participants.-Six healthy volunteers (four men and two women, aged 24 to 35 years) not taking any prescription or over-the-counter medications. Intervention.-After achieving a steady state while taking terfenadine (60 mg every 12 hours for 7 days), daily concomitant oral ketoconazole (200 mg every 12 hours) was added to the subjects' regimen. Pharmacokinetic profiles were obtained while subjects were taking terfenadine alone and after the addition of ketoconazole. Electrocardiograms were obtained at baseline, after 1 week of taking terfenadine alone, and at the time of the second pharmacokinetic profile after the addition of ketoconazole to the regimen. Main Outcome Measures.-Terfenadine and its acid metabolite serum concentrations and corrected QT intervals. Results.-All subjects had detectable levels of unmetabolized terfenadine after the addition of ketoconazole, which was associated with QT prolongation. Only two of the six subjects could complete the entire course of ketoconazole coadministration. Four subjects received a shortened duration of ketoconazole therapy because of significant electrocardiographic repolarization abnormalities. There was a significant change in the area under the curve of the acid metabolite of terfenadine after the addition of ketoconazole administration. Conclusions.-Ketoconazole alters the metabolism of terfenadine in normal men and women and results in the accumulation of unmetabolized parent drug, which is associated with significant prolongation of the corrected QT interval. This drug combination should be avoided. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,DIV CLIN PHARMACOL,4301 JONES BRIDGE RD,BETHESDA,MD 20814. WALTER REED ARMY MED CTR,DIV CARDIOL,WASHINGTON,DC 20307. US FDA,ROCKVILLE,MD 20857. RI Zamani, Kaveh/A-9182-2011 NR 28 TC 572 Z9 581 U1 1 U2 5 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 24 PY 1993 VL 269 IS 12 BP 1513 EP 1518 DI 10.1001/jama.269.12.1513 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA KR803 UT WOS:A1993KR80300023 PM 8445813 ER PT J AU WOOSLEY, RL CHEN, YW FREIMAN, JP GILLIS, RA AF WOOSLEY, RL CHEN, YW FREIMAN, JP GILLIS, RA TI MECHANISM OF THE CARDIOTOXIC ACTIONS OF TERFENADINE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TORSADES-DE-POINTES; FELINE VENTRICULAR MYOCYTES; EARLY AFTERDEPOLARIZATIONS; QT-INTERVAL; BLOCK AB Objectives and Methods.-To gain insight into possible mechanisms of and predisposing factors for torsades de pointes during terfenadine therapy, spontaneous reports in the US Food and Drug Administration's Spontaneous Reporting System database were examined. Based on the characteristics of the cases, in vitro cardiac electrophysiologic studies were conducted to test the hypothesis that terfenadine, and not its major metabolite, has actions similar to those of quinidine and is responsible for this form of cardiac toxicity. Design.-Spontaneous reports from the general medical community. Results.-As of April 1, 1992, 25 cases of torsades de pointes had been reported to the Food and Drug Administration's Spontaneous Reporting System. Predisposing factors in these cases indicated that the parent drug, but not its metabolite, may have actions similar to those of quinidine that are responsible for inducing arrhythmia. In vitro studies found that terfenadine is equipotent to quinidine as a blocker of the delayed rectifier potassium current in isolated feline myocytes. The metabolite, terfenadine carboxylate, did not inhibit this potassium current even at concentrations 30 times higher than the concentration of terfenadine producing a half-maximal effect. Conclusions.-Since blockade of the potassium channel did not occur with the major metabolite of terfenadine, episodes of torsades de pointes are most likely the result of a quinidinelike action of the parent drug and of factors that impair the normally rapid metabolism of terfenadine. Dosage restriction and awareness of the clinical conditions and drug interactions capable of inhibiting the metabolism of terfenadine are essential for prevention of this serious reaction. C1 US FDA,CTR DRUG EVALUAT & RES,DIV EPIDEMIOL & SURVEILLANCE,ROCKVILLE,MD 20857. RP WOOSLEY, RL (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,DIV CLIN PHARMACOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 28 TC 448 Z9 458 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 24 PY 1993 VL 269 IS 12 BP 1532 EP 1536 DI 10.1001/jama.269.12.1532 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA KR803 UT WOS:A1993KR80300026 PM 8445816 ER PT J AU PECK, CC TEMPLE, R COLLINS, JM AF PECK, CC TEMPLE, R COLLINS, JM TI UNDERSTANDING CONSEQUENCES OF CONCURRENT THERAPIES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID OXIDATION RP PECK, CC (reprint author), US FDA,CTR DRUG EVALUAT & RES,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. NR 13 TC 92 Z9 93 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 24 PY 1993 VL 269 IS 12 BP 1550 EP 1552 DI 10.1001/jama.269.12.1550 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA KR803 UT WOS:A1993KR80300031 PM 8445821 ER PT J AU PASTAKIA, KB TERLE, D PRODOUZ, KN AF PASTAKIA, KB TERLE, D PRODOUZ, KN TI PENICILLIN INHIBITS AGONIST-INDUCED EXPRESSION OF PLATELET SURFACE-MEMBRANE GLYCOPROTEINS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article RP PASTAKIA, KB (reprint author), US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAR 20 PY 1993 VL 677 BP 437 EP 439 DI 10.1111/j.1749-6632.1993.tb38810.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KX225 UT WOS:A1993KX22500054 PM 8494236 ER PT J AU MILLER, HI AF MILLER, HI TI BIOTECHNOLOGY IN JAPAN SO SCIENCE LA English DT Letter RP MILLER, HI (reprint author), US FDA,OFF BIOTECHNOL,ROCKVILLE,MD 20857, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 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 19 PY 1993 VL 259 IS 5102 BP 1678 EP 1678 DI 10.1126/science.8456289 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KT810 UT WOS:A1993KT81000005 PM 8456289 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI DRONABINOL APPROVED FOR USE IN ANOREXIA ASSOCIATED WITH WEIGHT-LOSS IN PATIENTS WITH AIDS 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 7 Z9 7 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 17 PY 1993 VL 269 IS 11 BP 1361 EP 1361 DI 10.1001/jama.269.11.1361 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KQ857 UT WOS:A1993KQ85700007 PM 8382752 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI WARNING ABOUT VIBRIO INFECTIONS AND RAW MOLLUSCAN SHELLFISH CONSUMPTION 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 7 Z9 7 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 17 PY 1993 VL 269 IS 11 BP 1361 EP 1361 DI 10.1001/jama.269.11.1361 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KQ857 UT WOS:A1993KQ85700005 PM 8382752 ER PT J AU NIGHTINGALE, SL AF NIGHTINGALE, SL TI INTERIM METHADONE-MAINTENANCE TREATMENT 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 7 Z9 7 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 17 PY 1993 VL 269 IS 11 BP 1361 EP 1361 DI 10.1001/jama.269.11.1361 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KQ857 UT WOS:A1993KQ85700006 PM 8382752 ER PT J AU LACOURCIERE, GM VAKHARIA, VN TAN, CP MORRIS, DI EDWARDS, GH MOOS, M ARMSTRONG, RN AF LACOURCIERE, GM VAKHARIA, VN TAN, CP MORRIS, DI EDWARDS, GH MOOS, M ARMSTRONG, RN TI INTERACTION OF HEPATIC-MICROSOMAL EPOXIDE HYDROLASE DERIVED FROM A RECOMBINANT BACULOVIRUS EXPRESSION SYSTEM WITH AN AZARENE OXIDE AND AN AZIRIDINE SUBSTRATE-ANALOG SO BIOCHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; GLUTATHIONE S-TRANSFERASE; ENZYMATIC HYDRATION; COVALENT STRUCTURE; COMPLEMENTARY-DNA; AZAARENE OXIDES; ALPHA-EPOXIDES; BETA-EPOXIDES; ARENE OXIDES; PROTEINS AB A recombinant baculovirus (vEHX) encoding rat hepatic microsomal epoxide hydrolase has been constructed. Infection of Spodoptera frugiperda (Sf9) cells with the recombinant virus results in the expression of the enzyme at a level estimated to be between 5% and 10% of the cellular protein. The enzyme, which can be purified in 15% yield by a simple three-step procedure involving detergent extraction, DEAE-cellulose chromatography, and removal of the detergent on hydroxylapatite, has physical and kinetic properties very close to those of the enzyme obtained from rat liver microsomes. The interaction of the enzyme with two nitrogen-containing analogues of the substrate phenanthrene 9,10-oxide (1) was investigated in order to delineate the contributions of the oxirane group and the hydrophobic surface of the substrate to substrate recognition. The enzyme exhibits altered kinetic properties toward 1,10-phenanthroline 5,6-oxide (2) in which the biphenyl group of 1 is replaced with a bipyridyl group, suggesting that hydrophobic interaction between the complementary surfaces of the substrate and active site has an influence on catalysis. The conjugate acid of the aziridine analogue of 1, phenanthrene 9,10-imine (3), in which the oxirane oxygen is replaced with NH, has a pK(a) of 6.1, which allows the characterization of both the neutral and protonated aziridine (3H+) as substrate analogues for the enzyme. The pH dependence of the solvolysis reveals that 3H+ rearranges to a 65/35 mixture of 9-aminophenanthrene and 9-amino-10-hydroxy-9,10-dihydrophenanthrene 10(3)-fold faster than does 3. The neutral aziridine is a competitive inhibitor (K(i) = 26 muM) of the enzyme at pH 8. The K(i) increases to 120 muM at pH 6.5, suggesting that 3H+ is not a transition-state analogue for the enzyme-catalyzed hydration of 1. Neither 3 nor 3H+ appears to be a substrate for the enzyme. The results are consistent with the notion that protonation of the oxirane oxygen is not an important aspect of transition state for the enzyme-catalyzed hydration of arene oxides. C1 MARYLAND BIOTECHNOL INST,CTR AGR BIOTECHNOL,DEPT CHEM & BIOCHEM,COLL PK,MD 20742. US FDA,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20892. UNIV MARYLAND,VIRGINIA MARYLAND REG COLL VET MED,COLL PK,MD 20742. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 FU NIGMS NIH HHS [GM30910] NR 38 TC 22 Z9 22 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 16 PY 1993 VL 32 IS 10 BP 2610 EP 2616 DI 10.1021/bi00061a019 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KR819 UT WOS:A1993KR81900019 PM 8383521 ER PT J AU OLSON, LD RENSHAW, CA ROTTEM, S BOAL, JH AF OLSON, LD RENSHAW, CA ROTTEM, S BOAL, JH TI ARGININE UTILIZATION BY MYCOPLASMA-FERMENTANS IS NOT REGULATED BY GLUCOSE-METABOLISM - A C-13-NMR STUDY SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE C-13-NMR; MYCOPLASMA-FERMENTANS; METABOLISM; ARGININE DEIMINASE; GLYCOLYSIS ID STREPTOCOCCUS-LACTIS; MONOPHOSPHATE; PATHWAY; AIDS AB C-13-NMR studies on the effect of glucose metabolism on arginine hydrolysis in Mycoplasma fermentans cells have been performed using a continuous perfusion technique. With this procedure we were able to show, in the presence of glucose, the rapid accumulation of lactic acid and, in the presence of arginine, the formation of citrulline that is apparently further metabolized. As the accumulation of lactate and the breakdown of arginine were observed in the simultaneous presence of both substrates, it is suggested that the glucose utilization has little or no effect on the deimination of arginine to citrulline. RP OLSON, LD (reprint author), US FDA,CTR BIOL EVALUAT & RES,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD MAR 15 PY 1993 VL 108 IS 1 BP 47 EP 51 PG 5 WC Microbiology SC Microbiology GA KU268 UT WOS:A1993KU26800010 PM 8472924 ER PT J AU FINBLOOM, DS LARNER, AC NAKAGAWA, Y HOOVER, DL AF FINBLOOM, DS LARNER, AC NAKAGAWA, Y HOOVER, DL TI CULTURE OF HUMAN MONOCYTES WITH GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR RESULTS IN ENHANCEMENT OF IFN-GAMMA RECEPTORS BUT SUPPRESSION OF IFN-GAMMA-INDUCED EXPRESSION OF THE GENE-IP-10 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC INFLAMMATORY ARTHRITIS; RECOMBINANT INTERFERON-GAMMA; GENE-EXPRESSION; CELL-LINES; ANTIBODIES; BINDING; IDENTIFICATION; ACTIVATION; INDUCTION; CYTOKINES AB The initiation and promulgation of chronic inflammation are controlled in part by the various proinflammatory and anti-inflammatory cytokines present at the site of injury. IFN-gamma and granulocyte-macrophage CSF (GM-CSF) are two cytokines that can contribute to the inflammatory state and possess both pro- and anti-inflammatory properties. However, the characterization of the interaction between GM-CSF-cultured monocytes and IFN-gamma is poorly documented. In this report we show that culture of human peripheral blood monocytes for up to 6 days in the presence of GM-CSF results in an eightfold increase in the level of IFN-gammaR expression, as determined by radioligand binding. The IFN-gammaR on these cells maintains a specificity typical of that observed in fresh monocytes. Only IFN-gamma, not IFN-alpha or -beta, blocks the binding of IFN-gamma to its receptor, and anti-IFN-gammaR antibodies block at least 80% of binding of IFN-gamma to these cultured cells. However, in spite of increased receptor expression, GM-CSF-cultured monocytes have a diminished response to IFN-gamma as measured by the induction of the gene for IP-10 (a member of the platelet factor-4/IL-8 family). On the other hand, IFN-gamma-induced activation of the DNA-binding protein FcRFgamma is maintained in GM-CSF-cultured monocytes. Therefore, suppression of IFN-gamma-mediated IP-10 induction is not the result of a global abrogation of signal transduction across the IFN-gammaR but a more selective inhibition that appears to occur downstream of the receptor. C1 WALTER REED ARMY INST RES,DEPT BACTERIAL DIS,WASHINGTON,DC 20307. RP FINBLOOM, DS (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 32 Z9 33 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 MAR 15 PY 1993 VL 150 IS 6 BP 2383 EP 2390 PG 8 WC Immunology SC Immunology GA KR934 UT WOS:A1993KR93400031 PM 8450219 ER PT J AU GOLDING, H DIMITROV, DS BLACKBURN, R MANISCHEWITZ, J BLUMENTHAL, R GOLDING, B AF GOLDING, H DIMITROV, DS BLACKBURN, R MANISCHEWITZ, J BLUMENTHAL, R GOLDING, B TI FUSION OF HUMAN B-CELL LINES WITH HIV-1 ENVELOPE-EXPRESSING T-CELLS IS ENHANCED BY ANTIGEN-SPECIFIC IG RECEPTORS - POSSIBLE MECHANISM FOR ELIMINATION OF GP120-SPECIFIC B-CELLS INVIVO SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING EPITOPE; LYMPHOTROPIC VIRUS; SYNCYTIA FORMATION; AIDS RETROVIRUS; HTLV-III/LAV; CD4 ANTIGEN; INFECTION; BINDING; GLYCOPROTEIN AB The possible contribution of Ag-specific Ig receptors on B cells to syncytium formation with HIV-1 envelope (env)-expressing cells was examined. A unique model system was designed that used anti-TNP/TNP interactions between a panel of TNP-specific human B cell lines and TNP-haptenated HIV-1 env-expressing T cells. The prototype B cell line 1:13 (CD4dull) produced few syncytia with vaccinia gp120/41-infected CD4- T cell effectors. However, TNP-haptenation of the HIV-1 env-expressing cells resulted in a five- to 10-fold increase in syncytium formation. The ''enhanced'' syncytia were blocked by OKT4A mAb, soluble CD4, anti-TNP serum, and TNP-BSA, suggesting a role for both CD4 and Ig receptors. In contrast, the number of syncytia formed between CD4+ CEM T cells and TNP-haptenated effectors was reduced by 30 to 40%, compared with the unhaptenated effectors, suggesting that a fraction of the TNP haptens bound close to the CD4 binding regions on the gp120 envelope, which was confirmed by other experiments. The possibility that B cells specific for the CD4 binding site on HIV-1 gp120 may be involved in syncytium formation with HIV-1 env-expressing cells was tested by screening a panel of five hybrid B cell lines from HIV-1-seropositive individuals. One of these lines produced anti-gp120 antibodies, which bound near the CD4 binding site, and also formed syncytia with HIV-1 env-expressing cells. This study suggests that, in addition to CD4 receptors, certain B cell Ig receptors that bind to gp120 may induce conformational changes leading to cell fusion and their elimination. C1 NCI,LMB,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. RP GOLDING, H (reprint author), US FDA,CBER,DIV VIROL,BLDG 29A,ROOM 2C15,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 2 Z9 2 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 MAR 15 PY 1993 VL 150 IS 6 BP 2506 EP 2516 PG 11 WC Immunology SC Immunology GA KR934 UT WOS:A1993KR93400044 PM 7680694 ER PT J AU HOWARD, OMZ CLOUSE, KA SMITH, C GOODWIN, RG FARRAR, WL AF HOWARD, OMZ CLOUSE, KA SMITH, C GOODWIN, RG FARRAR, WL TI SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR - INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS ID PROMONOCYTE CELL-LINE; LONG TERMINAL REPEAT; FACTOR-ALPHA; MOLECULAR-CLONING; INTERFERON-ALPHA; BINDING PROTEIN; SERUM LEVELS; KAPPA-B; EXPRESSION; HIV-1 AB The inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) has been shown to stimulate human immunodeficiency virus type 1 (HIV-1) replication in both chronically and acutely infected T lymphocytes and monocytes. Transcriptional activation of the HIV long terminal repeat and subsequent increase in virus production are linked to TNF activation of the cellular transcription factor NF-kappaB. Here we report the use of two forms of soluble recombinant type 1 (p80) TNF receptor to inhibit TNF-induced HIV activation in vitro. One receptor form is a monomer containing the entire 236 residues of the extracellular (ligand-binding) portion of p80. A second receptor form is a chimeric homodimer containing these residues fused to a truncated human IgG1 immunoglobulin heavy chain and, thus, resembles a bivalent antibody without light chains. These recombinant receptor proteins were tested for their ability to inhibit TNF-alpha-induced expression of HIV-1 in chronically infected human cell lines. We also examined the ability of the soluble receptors to limit the activation of the HIV-long terminal repeat transcription. The soluble TNF receptor dimer was most effective at blocking TNF-alpha-induced HIV-1 expression in both monocytoid and lymphoid cells. The molar ratio of TNF-receptor dimer to TNF-alpha found to be most effective was, at least, 5:1. We conclude that at specific TNF/soluble TNF-receptor dimer ratios, TNF-alpha-induced HIV-1 transcription and expression can be limited in vitro. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,POB B,FREDERICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20014. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-74102] NR 39 TC 61 Z9 61 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 15 PY 1993 VL 90 IS 6 BP 2335 EP 2339 DI 10.1073/pnas.90.6.2335 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KT370 UT WOS:A1993KT37000052 PM 7681592 ER PT J AU EPSTEIN, SL MISPLON, JA LAWSON, CM SUBBARAO, EK CONNORS, M MURPHY, BR AF EPSTEIN, SL MISPLON, JA LAWSON, CM SUBBARAO, EK CONNORS, M MURPHY, BR TI PROTECTION OF MHC CLASS-I-DEFICIENT MICE AGAINST INFLUENZA A INFECTION BY VACCINIA-INFLUENZA RECOMBINANTS EXPRESSING HEMAGGLUTININ AND NEURAMINIDASE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CBER,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 65 EP 65 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000215 ER PT J AU GOLDING, H DIMITROV, D BLUMENTHAL, R GOLDING, B AF GOLDING, H DIMITROV, D BLUMENTHAL, R GOLDING, B TI FUSION OF HUMAN B-CELLS WITH HIV-1 ENVELOPE EXPRESSING T-CELLS CAN BE INDUCED BY ANTIGEN SPECIFIC IMMUNOGLOBULIN (IG) RECEPTORS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,LMMB,BETHESDA,MD 20892. US FDA,CBER,DIV VIROL,WASHINGTON,DC 20204. US FDA,CBER,DIV HEMATOL,WASHINGTON,DC 20204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 73 EP 73 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000247 ER PT J AU ROSENBERG, AS SECHLER, JMG HARTLEY, JW MORSE, HC AF ROSENBERG, AS SECHLER, JMG HARTLEY, JW MORSE, HC TI INDUCTION OF INVIVO T-CELL DYSFUNCTION IN MAIDS DEPENDS ON INFECTION BY DISEASE INDUCING DEFECTIVE GENOME, NOT HELPER VIRUS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CBER,DIV HEMATOL PROD,BETHESDA,MD 20892. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 76 EP 76 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000259 ER PT J AU SECHLER, JMG CLOUSE, KA STREBEL, K WEIH, KA ROSENBERG, AS AF SECHLER, JMG CLOUSE, KA STREBEL, K WEIH, KA ROSENBERG, AS TI EFFECT OF RESTRICTION ENDONUCLEASES ON HIV-INFECTION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 76 EP 76 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000260 ER PT J AU GOLDING, B INMAN, J ZAITSEVA, M GOLDING, H AF GOLDING, B INMAN, J ZAITSEVA, M GOLDING, H TI BRUCELLA-ABORTUS, A POTENTIAL CARRIER FOR HIV-1 VACCINE STIMULATES HUMAN TH-1 CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CBER,DIV HEMATOL & VIROL,BETHESDA,MD 20014. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 80 EP 80 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000277 ER PT J AU PECK, CC AF PECK, CC TI CONCENTRATION DRIVEN EARLY CLINICAL-STUDIES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CDER,ROCKVILLE,MD 20857. NR 1 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 171 EP 171 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000593 ER PT J AU MELLERICKDRESSLER, DM KASSIS, JA ZHANG, SD ODENWALD, WF AF MELLERICKDRESSLER, DM KASSIS, JA ZHANG, SD ODENWALD, WF TI CASTOR ENCODES A NOVEL ZINC FINGER PROTEIN REQUIRED FOR THE DEVELOPMENT OF A SUBSET OF CNS AXONS IN DROSOPHILA SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 262 EP 262 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000906 ER PT J AU RIDGE, J TERLE, D DRAGUNSKY, E LEVENBOOK, I AF RIDGE, J TERLE, D DRAGUNSKY, E LEVENBOOK, I TI DIFFERENTIATING AND ANTIPROLIFERATIVE EFFECTS OF GAMMA-IFN AND NGF ON SUBPOPULATIONS IN A NEUROBLASTOMA CELL-LINE - FLOW CYTOMETRIC AND MORPHOLOGICAL ANALYSIS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 13 PY 1993 SU 17D BP 266 EP 266 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KV880 UT WOS:A1993KV88000919 ER PT J AU MERKATZ, RB AF MERKATZ, RB TI THE BREAST-IMPLANT CONTROVERSY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID MASTECTOMY RP MERKATZ, RB (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 1993 VL 328 IS 10 BP 733 EP 734 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA KQ861 UT WOS:A1993KQ86100018 PM 8433740 ER PT J AU KESSLER, DA AF KESSLER, DA TI THE BREAST-IMPLANT CONTROVERSY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP KESSLER, DA (reprint author), US FDA,ROCKVILLE,MD 20857, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 1993 VL 328 IS 10 BP 734 EP 734 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KQ861 UT WOS:A1993KQ86100020 ER PT J AU SUTKOWSKI, EM MAHER, F LAURENZA, A SIMPSON, IA SEAMON, KB AF SUTKOWSKI, EM MAHER, F LAURENZA, A SIMPSON, IA SEAMON, KB TI INTERACTION OF 7-BROMOACETYL-7-DESACETYLFORSKOLIN, AN ALKYLATING DERIVATIVE OF FORSKOLIN, WITH BOVINE BRAIN ADENYLYL CYCLASE AND HUMAN ERYTHROCYTE GLUCOSE TRANSPORTER SO BIOCHEMISTRY LA English DT Article ID H-3 FORSKOLIN; RAT-BRAIN; CATALYTIC UNIT; BINDING-SITES; F-ACTIN; PURIFICATION; MEMBRANES; PROTEIN; ALPHA; SEQUENCE AB 7-Bromoacetyl-7-desacetylforskolin (BrAcFsk), an alkylating derivative of forskolin, activated adenylyl cyclase and irreversibly blocked high affinity forskolin binding sites in human platelet membranes and rat brain membranes (Laurenza et al., 1990). Photoincorporation of an iodinated arylazido derivative of forskolin, I-125-6-AIPP-Fsk, into adenylyl cyclase in bovine brain membranes was irreversibly inhibited by BrAcFsk but not by 1,9-dideoxy-BrAcFsk, suggesting that BrAcFsk was reacting specifically with a nucleophilic group(s) at the forskolin binding site of adenylyl cyclase. Immunoblotting with antiforskolin antiserum demonstrated that partially purified bovine brain adenylyl cyclase had incorporated BrAcFsk. The interaction of BrAcFsk with the glucose transporter in human erythrocyte membranes was examined in a similar manner. Photoincorporation of I-125-7-AIPP-Fsk, an iodinated arylazido derivative of forskolin which is specific for the glucose transporter, into the glucose transporter was not irreversibly inhibited by BrAcFsk, suggesting that, in contrast to adenylyl cyclase, there is no reactive nucleophilic group at the forskolin binding site on the human erythrocyte glucose transporter. The immunoblotting procedure with antiforskolin antiserum confirmed that BrAcFsk was not covalently attached to human erythrocyte glucose transporter. C1 US FDA,DIV BIOCHEM & BIOPHYS,MOLEC PHARMACOL LAB,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NIDDKD,MCNEB,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD 20892. NR 44 TC 4 Z9 4 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 9 PY 1993 VL 32 IS 9 BP 2415 EP 2422 DI 10.1021/bi00060a037 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KQ860 UT WOS:A1993KQ86000037 PM 8443181 ER PT J AU CAVAILLECOLL, M MIELACH, FA AF CAVAILLECOLL, M MIELACH, FA TI CHOICE OF CYCLOPHOSPHAMIDE DOSE IN BABOON-TO-HUMAN LIVER-TRANSPLANTATION SO LANCET LA English DT Letter RP CAVAILLECOLL, M (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857, USA. NR 5 TC 0 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAR 6 PY 1993 VL 341 IS 8845 BP 639 EP 639 DI 10.1016/0140-6736(93)90408-9 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KQ234 UT WOS:A1993KQ23400058 PM 7679768 ER PT J AU RABEN, N SHERMAN, J MILLER, F MENA, H PLOTZ, P AF RABEN, N SHERMAN, J MILLER, F MENA, H PLOTZ, P TI A 5' SPLICE JUNCTION MUTATION LEADING TO EXON DELETION IN AN ASHKENAZIC JEWISH FAMILY WITH PHOSPHOFRUCTOKINASE DEFICIENCY (TARUI DISEASE) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; TAY-SACHS DISEASE; SOMATIC-CELL HYBRIDS; PRE-MESSENGER RNA; NONSENSE MUTATIONS; TERMINATION CODON; GENE; SITE; IDENTIFICATION; ISOZYMES AB A deficiency of the muscle isoform of the enzyme, phosphofructokinase (PFK, EC 2.7.1.11), leads to an illness (glycogenosis, Type VII) characterized by myopathy and hemolysis. A patient with this disease and an affected sister were found to have a G to A substitution at the 5' donor site of intron 5 of the PFK-M gene. This mutation led to a splicing defect: a complete deletion of the preceding exon in the patient's mRNA. The patient, an affected sister, and related and unrelated family members, who were of Ashkenazic Jewish background, were screened for the mutation by denaturing gradient gel electrophoresis and by allele specific hybridization of genomic DNA. The affected sisters are homozygous for the mutation, and their children, who are unaffected, are heterozygous. The only previously characterized genetic defect in this disease, found in a Japanese patient, was a G to T mutation at the beginning of intron 15 with splicing to a cryptic site within exon 15 (1). Both mutations lead to in-frame deletions, but of different parts of the protein. The differences between the two aberrant proteins may account for clinical differences between our patients and the Japanese patient. C1 US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT NEUROPATHOL,WASHINGTON,DC 20306. RP RABEN, N (reprint author), NIAMSD,ARTHRITIS & RHEUMAT BRANCH,BETHESDA,MD 20892, USA. OI Miller, Frederick/0000-0003-2831-9593 NR 48 TC 43 Z9 43 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 1993 VL 268 IS 7 BP 4963 EP 4967 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400061 PM 8444874 ER PT J AU NICHOLLS, PJ JOHNSON, VG ANDREW, SM HOOGENBOOM, HR RAUS, JCM YOULE, RJ AF NICHOLLS, PJ JOHNSON, VG ANDREW, SM HOOGENBOOM, HR RAUS, JCM YOULE, RJ TI CHARACTERIZATION OF SINGLE-CHAIN ANTIBODY (SFV)-TOXIN FUSION PROTEINS PRODUCED INVITRO IN RABBIT RETICULOCYTE LYSATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN TRANSFERRIN RECEPTOR; DIPHTHERIA-TOXIN RECEPTOR; FRAGMENT D-DIMER; PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; RECOMBINANT IMMUNOTOXIN; GENETIC CONSTRUCTION; OVERLAP EXTENSION; VARIABLE DOMAINS; PLASMA-MEMBRANE AB Chimeric proteins consisting of a fusion between binding-deficient mutants of diphtheria toxin (DT) or Pseudomonas exotoxin A (PE) and a single-chain antibody (E6 sFv) against the human transferrin receptor (TfnR) were expressed in a rabbit reticulocyte lysate system. Molecules utilizing PE40 (the carboxyl terminus 40 kDa of PE, lacking the binding domain) exhibited significant E6 sFv-mediated, cell type-specific cytotoxicity (IC50 1 x 10(-10) M) against a human erythroleukemia-derived cell line, K562. In contrast, a fusion protein between the same sFv and a DT mutant, DTM1 (containing two amino acid substitutions in the binding domain [S(508)F, S(525)F]) was not significantly cytotoxic, despite being enzymatically active. A tripartite protein in the form NH2-DTM1-E6 sFv-PE40-COOH exhibited cytotoxicity comparable to that of the PE40-sFv fusion (IC50 1 x 10(-10) M), suggesting that the deficit in activity of DTM1-sFv is not a function of misfolding of the sFv moiety or of a reduced ability to bind TfnR. In contrast to DTM1-E6 sFv, a fusion protein between a second DT mutant, CRM 107 [S(525)F], and the E6 sFv was specifically cytotoxic (IC50 1 X 10(-9) M), and toxicity could be blocked by addition of excess E6 antibody. The cell-free in vitro expression system we describe is rapid and may be used to express functional toxin-sFv fusion proteins. No protein refolding procedures are required, and the technique may be used to express proteins which, due to restrictions imposed on manipulation of toxin-encoding genes in Escherichia coli, could not be produced by more conventional methods. C1 US FDA,CBER,DIV BACTERIAL PROD,BACTERIAL TOXINS LAB,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. LIMBURGS UNIV CENTRUM,DR L WILLEMS INST,B-3610 DIEPENBEEK,BELGIUM. LIMBURGS UNIV CENTRUM,DEPT WNIF,B-3610 DIEPENBEEK,BELGIUM. RP NICHOLLS, PJ (reprint author), NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20892, USA. NR 55 TC 32 Z9 32 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 1993 VL 268 IS 7 BP 5302 EP 5308 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KP884 UT WOS:A1993KP88400105 PM 8444903 ER PT J AU BEAUCAGE, SL IYER, RP AF BEAUCAGE, SL IYER, RP TI THE FUNCTIONALIZATION OF OLIGONUCLEOTIDES VIA PHOSPHORAMIDITE DERIVATIVES SO TETRAHEDRON LA English DT Review ID SOLID-PHASE SYNTHESIS; SINGLE-STRANDED-DNA; POLYMERASE CHAIN-REACTION; TRIPLE-HELIX FORMATION; CHOLESTERYL-CONJUGATED OLIGONUCLEOTIDES; OPTICAL SPECTROSCOPIC MEASUREMENTS; SITE-SPECIFIC FUNCTIONALIZATION; CONVERTIBLE NUCLEOSIDE APPROACH; SEQUENCE-SPECIFIC RECOGNITION; RADIOACTIVE LABEL ATTACHMENT RP BEAUCAGE, SL (reprint author), US FDA,DIV BIOCHEM & BIOPHYS,CTR BIOLOG EVALUAT & RES,BETHESDA,MD 20892, USA. NR 258 TC 247 Z9 249 U1 2 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD MAR 5 PY 1993 VL 49 IS 10 BP 1925 EP 1963 DI 10.1016/S0040-4020(01)86295-5 PG 39 WC Chemistry, Organic SC Chemistry GA KQ538 UT WOS:A1993KQ53800001 ER PT J AU CONTRERA, JF AUB, D BARBEHENN, E BELAIR, E CHEN, C EVONIUK, G MAINIGI, K MIELACH, F SANCILIO, L AF CONTRERA, JF AUB, D BARBEHENN, E BELAIR, E CHEN, C EVONIUK, G MAINIGI, K MIELACH, F SANCILIO, L TI A RETROSPECTIVE COMPARISON OF THE RESULTS OF 6-MONTH AND 12-MONTH NON-RODENT TOXICITY STUDIES SO ADVERSE DRUG REACTIONS AND TOXICOLOGICAL REVIEWS LA English DT Review DE DOG CHRONIC TOXICITY STUDY; DURATION OF TOXICITY; 12 MONTHS AND 6 MONTHS RP CONTRERA, JF (reprint author), US FDA,CTR DRUG EVALUAT & RES,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 7 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0260-647X J9 ADVERSE DRUG REACT T JI Adverse Drug React. Toxicol. Rev. PD SPR PY 1993 VL 12 IS 1 BP 63 EP 76 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LD155 UT WOS:A1993LD15500006 PM 8513078 ER PT J AU FREIMAN, JP HELFERT, KE HAMRELL, MR STEIN, DS AF FREIMAN, JP HELFERT, KE HAMRELL, MR STEIN, DS TI HEPATOMEGALY WITH SEVERE STEATOSIS IN HIV-SEROPOSITIVE PATIENTS SO AIDS LA English DT Article DE HEPATOMEGALY; STEATOSIS; HIV; ZIDOVUDINE ID IMMUNE-DEFICIENCY SYNDROME; HUMAN-IMMUNODEFICIENCY-VIRUS; SYNDROME AIDS; REYES-SYNDROME; DRUG-ABUSE; LIVER; INFECTION; DISEASE AB Objective. To describe death attributed to severe hepatomegaly and macrovesicular steatosis without inflammation or necrosis in HIV-seropositive patients without AIDS. Patients: Patients from the AIDS Clinical Trials Group (ACTG) Adverse Reactions and the Food and Drug Administration's (FDA) Spontaneous Report databases. Results: Six fatal and two non-fatal cases in which no known cause of hepatic steatosis could be found were identified. With one possible exception, none of the six fatal cases had a diagnosis of AIDS and all were in reasonable nutritional status (as indicated by weight and/or serum albumin); the majority were mildly to moderately overweight. All had received at least 6 months of antiretroviral therapy, and all had gastrointestinal complaints without other non-hepatic abdominal pathology. At least three out of the six had no history of progressively abnormal liver function tests until a few weeks prior to the onset of symptoms and subsequent death. Further investigation of the FDA and ACTG databases identified two similar but non-fatal cases in which abnormalities resolved after cessation of antiretroviral therapy. Conclusions: The cases described represent a degree of hepatic abnormalities that has not been reported previously in HIV-seropositive patients, and are probably an underestimate of actual incidence, since patients with possible etiologies of liver disease were excluded from the clinical history, laboratory, microbiologic, or histologic examination. The etiology of hepatic disease may be associated with antiretroviral therapy, HIV, or an unidentifiable infection, and requires further investigation. C1 NIAID,DIV AIDS,MED BRANCH,6003 EXECUT BLVD,RM 2C25,ROCKVILLE,MD 20852. US FDA,CTR DRUG EVALUAT & RES,OFF EPIDEMIOL & BIOSTAT,ROCKVILLE,MD 20857. NIAID,PHARMACEUT & REGULATORY AFFAIRS BRANCH,ROCKVILLE,MD. NR 31 TC 123 Z9 124 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 MAR PY 1993 VL 7 IS 3 BP 379 EP 385 DI 10.1097/00002030-199303000-00012 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA KT079 UT WOS:A1993KT07900012 PM 8471200 ER PT J AU RHEINSTEIN, PH AF RHEINSTEIN, PH TI UPDATE ON FOOD LABELING SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material RP RHEINSTEIN, PH (reprint author), US FDA,MED STAFF,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD MAR PY 1993 VL 47 IS 4 BP 979 EP 982 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA KQ556 UT WOS:A1993KQ55600021 PM 8438688 ER PT J AU MOORE, RM DAVIS, YM KACZMAREK, RG AF MOORE, RM DAVIS, YM KACZMAREK, RG TI AN OVERVIEW OF OCCUPATIONAL HAZARDS AMONG VETERINARIANS, WITH PARTICULAR REFERENCE TO PREGNANT-WOMEN SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Review ID UNITED-STATES VETERINARIANS; HEALTH-CARE WORKERS; ETHYLENE-OXIDE; MORTALITY; PATTERNS; EXPOSURE; CANCER; COHORT AB Veterinarians are challenged by an imposing group of occupational hazards, including exposure to ionizing radiation, injury, infectious agents, and chemicals. In this paper, the health hazards in the typical veterinary practice are inventoried, and the risks of each are assessed. During the past few decades, there has been a significant increase in women entering the veterinary profession. Information is presented concerning the impact of various occupational hazards on the health of female practitioners and paraprofessionals, particularly in regard to the reproductive system. Many of the occupational hazards are exclusively, or more significantly, detrimental to females (particularly when pregnant) and to their unborn. Women must be aware of and avoid these hazards in their clinical environment. The purpose of this review is to assist practitioners in identifying and assessing the hazards in their practice and determining what steps must be taken to eliminate or reduce them. C1 US PHS,OFF SURG GEN,ROCKVILLE,MD 20857. US FDA,CDRH,DBS,OST,PUBL HLTH SERV,ROCKVILLE,MD 20857. US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20852. RP MOORE, RM (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,EPIDEMIOL BRANCH,ROCKVILLE,MD 20857, USA. NR 62 TC 36 Z9 37 U1 1 U2 4 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 SN 0002-8894 J9 AM IND HYG ASSOC J JI Am. Ind. Hyg. Assoc. J. PD MAR PY 1993 VL 54 IS 3 BP 113 EP 120 DI 10.1080/15298669391354423 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA KQ289 UT WOS:A1993KQ28900006 PM 8447254 ER PT J AU HIRSHFIELD, KM TOPTYGIN, D PACKARD, BS BRAND, L AF HIRSHFIELD, KM TOPTYGIN, D PACKARD, BS BRAND, L TI DYNAMIC FLUORESCENCE MEASUREMENTS OF 2-STATE SYSTEMS - APPLICATIONS TO CALCIUM-CHELATING PROBES SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID TIME-RESOLVED FLUORESCENCE; CYTOSOLIC FREE CA-2+; INDICATORS; QUIN2 C1 JOHNS HOPKINS UNIV, DEPT BIOL, MUDD HALL, 34TH & N CHARLES ST, BALTIMORE, MD 21218 USA. US FDA, CBER, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM07231, GM11632] NR 25 TC 22 Z9 22 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR PY 1993 VL 209 IS 2 BP 209 EP 218 DI 10.1006/abio.1993.1109 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA KR444 UT WOS:A1993KR44400001 PM 8470792 ER PT J AU KELLEY, I FREEMAN, JP EVANS, FE CERNIGLIA, CE AF KELLEY, I FREEMAN, JP EVANS, FE CERNIGLIA, CE TI IDENTIFICATION OF METABOLITES FROM THE DEGRADATION OF FLUORANTHENE BY MYCOBACTERIUM SP STRAIN PYR-1 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; RING FISSION-PRODUCTS; MUTAGENIC METABOLITES; MICROBIAL-METABOLISM; BACTERIUM; OXIDATION; CREOSOTE; SEDIMENT; INVITRO; SOOT AB Mycobacterium sp. strain PYR-1, previously shown to extensively mineralize high-molecular-weight polycyclic aromatic hydrocarbons in pure culture and in sediments, degrades fluoranthene to 9-fluorenone-1-carboxylic acid. In this study, 10 other fluoranthene metabolites were isolated from ethyl acetate extracts of the culture medium by thin-layer and high-performance liquid chromatographic methods. On the basis of comparisons with authentic compounds by UV spectrophotometry and thin-layer chromatography as well as gas chromatography-mass spectral and proton nuclear magnetic resonance spectral analyses, the metabolites were identified as 8-hydroxy-7-methoxyfluoranthene, 9-hydroxyfluorene, 9-fluorenone, 1-acenaphthenone, 9-hydroxy-1-fluorenecarboxylic acid, phthalic acid, 2-carboxybenzaldehyde, benzoic acid, phenylacetic acid, and adipic acid. Authentic 9-hydroxyfluorene and 9-fluorenone were metabolized by Mycobacterium sp. strain PYR-1. A pathway for the catabolism of fluoranthene by Mycobacterium sp. strain PYR-1 is proposed. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. NR 39 TC 104 Z9 110 U1 4 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 1993 VL 59 IS 3 BP 800 EP 806 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA KQ123 UT WOS:A1993KQ12300023 PM 8481006 ER PT J AU HELLER, DN SCHENCK, FJ AF HELLER, DN SCHENCK, FJ TI PARTICLE BEAM LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY WITH NEGATIVE-ION CHEMICAL IONIZATION FOR THE CONFIRMATION OF IVERMECTIN RESIDUE IN BOVINE-MILK AND LIVER SO BIOLOGICAL MASS SPECTROMETRY LA English DT Article ID FLUORESCENCE DETECTION; CATTLE AB Particle beam liquid chromatography/mass spectrometry (LC/MS) using negative ion chemical ionization was applied to the analysis of ivermectin residue in bovine milk and liver. Samples were prepared by liquid/liquid extraction followed by alumina B solid-phase extraction clean-up. On-line LC/MS of extracts was carried out on a C-18 bonded silica column. Signals were observed from on-column injections of 4 ng dihydro-avermectin B1a (H2B1a) in extracts equivalent to 2 ml milk or 0.3 g liver. The specificity required for a regulatory confirmation procedure was achieved by monitoring the H2B1a molecular ion and four fragment ions. Ion chromatogram peak areas were at least three times greater than control samples integrated over the same time window. Coeluting matrix compounds enhanced the response and altered the abundance pattern of H2B1a. To compensate for this matrix effect, control milk extracts were spiked with H2B1a standard and used for the abundance matching requirement of regulatory confirmation. C1 US FDA,BALTIMORE DIST OFF,BALTIMORE,MD 21201. RP HELLER, DN (reprint author), US FDA,CTR VET MED,OFF SCI,BELTSVILLE,MD 20705, USA. NR 24 TC 32 Z9 33 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9306 J9 BIOL MASS SPECTROM JI Biol. Mass Spectrom. PD MAR PY 1993 VL 22 IS 3 BP 184 EP 193 DI 10.1002/bms.1200220308 PG 10 WC Biophysics; Spectroscopy SC Biophysics; Spectroscopy GA KQ249 UT WOS:A1993KQ24900006 PM 8461342 ER PT J AU GERRARD, TL THORPE, R JEFFCOATE, S REYNOLDS, C AF GERRARD, TL THORPE, R JEFFCOATE, S REYNOLDS, C TI BIOLOGICAL POTENCY STANDARDS FOR CYTOKINES AND GROWTH-FACTORS SO BIOLOGICALS LA English DT Note C1 NATL INST BIOL STAND & CONTROLS,WHO,INT LAB BIOL STANDARDISAT,LONDON,ENGLAND. NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. RP GERRARD, TL (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. RI Thorpe, Robin/E-6853-2013 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 1993 VL 21 IS 1 BP 77 EP 79 DI 10.1006/biol.1993.1049 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA LV059 UT WOS:A1993LV05900007 PM 8217121 ER PT J AU HUNG, HMJ CHI, GYH LIPICKY, RJ AF HUNG, HMJ CHI, GYH LIPICKY, RJ TI TESTING FOR THE EXISTENCE OF A DESIRABLE DOSE COMBINATION SO BIOMETRICS LA English DT Article DE AVE TEST; MAX TEST; NUISANCE PARAMETER; POWER; SIGNIFICANCE LEVEL; TYPE-I ERROR PROBABILITY ID THERAPY AB We consider the problem of studying several dose combinations of two drugs for a therapeutic endpoint in a multilevel factorial clinical trial. Two test statistics are constructed to test whether there exists at least one dose combination that is more effective than its component doses. Their distributions involve nuisance parameters quantifying the mean differences among the doses of the two component drugs. It is shown that their power functions achieve maxima as all the nuisance parameters approach infinity in absolute value. The significance levels of the two tests are derived and two alpha-level tests are proposed. Tables are given to provide the alpha-level critical values for these tests and to gain insights into their power performances. C1 US FDA,CTR DRUG EVALUAT & RES,DIV CARDIORENAL DRUG PROD,ROCKVILLE,MD 20857. RP HUNG, HMJ (reprint author), US FDA,CTR DRUG EVALUAT & RES,STAT EVALUAT & RES BRANCH,DIV BIOMETR,ROCKVILLE,MD 20857, USA. NR 11 TC 31 Z9 31 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 MAR PY 1993 VL 49 IS 1 BP 85 EP 94 DI 10.2307/2532604 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LB230 UT WOS:A1993LB23000008 PM 8513112 ER PT J AU BARTON, CN BRAUNBERG, RC FRIEDMAN, L AF BARTON, CN BRAUNBERG, RC FRIEDMAN, L TI NONLINEAR STATISTICAL-MODELS FOR THE JOINT ACTION OF TOXINS SO BIOMETRICS LA English DT Article DE ADDITIVE MODELS; ANTAGONISM; INDEPENDENT ACTION; INTERACTION; MIXTURES; SIMILAR ACTION; SYNERGISM AB A general approach using nonlinear regression models is presented for evaluating additivity, synergism, and antagonism of mixtures of toxins for proportions and ratio-scale response measures. This approach provides several advantages over the analysis methods typically used, which involve linear regression with logits or probits. A single model fit is performed, rather than a multistep procedure. Nonadditive alternative models can be easily constructed and tested against the appropriate additive models. The approach avoids the use of data ''adjustments'' for nonzero background response rates. The analyses are performed in the natural response metric, making interpretation straightforward. Also, the nonlinear regression model can be reparameterized to provide more meaningful primary parameters. C1 US FDA,CTR FOOD SAFETY & APPL NUTR,DIV TOXICOL RES,WASHINGTON,DC 20204. RP BARTON, CN (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MATH,HFS-706,WASHINGTON,DC 20204, USA. NR 26 TC 12 Z9 12 U1 1 U2 1 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 1993 VL 49 IS 1 BP 95 EP 105 DI 10.2307/2532605 PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA LB230 UT WOS:A1993LB23000009 PM 8513113 ER PT J AU VANDERVEEN, JE AF VANDERVEEN, JE TI HEALTH AND NUTRITION SO CEREAL FOODS WORLD LA English DT Article RP VANDERVEEN, JE (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,OFF PLANT & DAIRY FOODS & BEVERAGES,WASHINGTON,DC 20204, 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 MAR PY 1993 VL 38 IS 3 BP 161 EP 162 PG 2 WC Food Science & Technology SC Food Science & Technology GA KT996 UT WOS:A1993KT99600009 ER PT J AU MACLEOD, MC QING, WG POWELL, KL DAYLONG, A EVANS, FE AF MACLEOD, MC QING, WG POWELL, KL DAYLONG, A EVANS, FE TI REACTION OF NONTOXIC, POTENTIALLY CHEMOPREVENTIVE PURINETHIOLS WITH A DIRECT-ACTING, ELECTROPHILIC CARCINOGEN, BENZO[A]PYRENE-7,8-DIOL-9,10-EPOXIDE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; BENZO(A)PYRENE DIOL-EPOXIDE; MAGNETIC-RESONANCE; DNA; INHIBITION; BINDING; 6-MERCAPTOPURINE; HYDROLYSIS; EPIDERMIS; ADDUCT AB Several nontoxic purinethiols have been shown to block the ability of the carcinogen 7-r,8-t-dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) to bind covalently to DNA in Chinese hamster ovary cells. Two of these compounds also block BPDE-induced tumorigenesis in a two-stage mouse skin carcinogenesis model. The suggested mode of action of the purinethiols is through scavenging the electrophilic carcinogen by way of covalent reaction with the purinethiol. In the present work, we demonstrate that a series of five purinethiols (2,6-dithiopurine, thiopurinol, 6-thioxanthine, 2-mercaptopurine, and 9-methyl-6-mercaptopurine) react covalently in vitro with BPDE. The adducts formed have been characterized by UV-visible spectroscopy, solvent partitioning, and NMR spectroscopy; they result from addition of the thiol moiety at the 10-carbon of BPDE. Studies of the effects of Tris buffer and temperature on product ratios at completion of reaction indicate that the two major reaction pathways, hydrolysis of the epoxide and adduct formation, do not share a common rate-determining step. This suggests that the reaction mechanism for adduct formation is through S(N)2 attack of the thiol moiety at the 10 position of BPDE. The activation energies for the reaction of 5-purinethiols with various combinations of substituents at the 2 and 6 positions are all very similar, implying closely similar transition states. For compounds with a low pK(a) (2,6-dithiopurine, 2-mercaptopurine, and 6-thioxanthine) the most important reactant at physiological pH is the thiolate anion. However, for compounds with pK(a)'s above 8, the physiologically important reactions appear to be more complicated. C1 NATL CTR TOXICOL RES,DEPT BIOCHEM TOXICOL,JEFFERSON,AR 72079. RP MACLEOD, MC (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CARCINOGENESIS,SCI PK RES DIV,BOX 389,SMITHVILLE,TX 78957, USA. NR 22 TC 17 Z9 18 U1 0 U2 1 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 MAR-APR PY 1993 VL 6 IS 2 BP 159 EP 167 DI 10.1021/tx00032a004 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KT721 UT WOS:A1993KT72100004 PM 8477006 ER PT J AU ZHANG, J YU, ZX FUJITA, S YAMAGUCHI, ML FERRANS, VJ AF ZHANG, J YU, ZX FUJITA, S YAMAGUCHI, ML FERRANS, VJ TI INTERSTITIAL DENDRITIC CELLS OF THE RAT-HEART - QUANTITATIVE AND ULTRASTRUCTURAL-CHANGES IN EXPERIMENTAL MYOCARDIAL-INFARCTION SO CIRCULATION LA English DT Article DE IMMUNOHISTOCHEMISTRY; MHC ANTIGENS; MONOCLONAL ANTIBODIES; T-HELPER LYMPHOCYTES ID HISTOCOMPATIBILITY COMPLEX ANTIGENS; CLASS-II; MONOCLONAL ANTIBODY; ALLOGRAFT-REJECTION; IMMUNE-RESPONSE; LYMPHOCYTES-T; EXPRESSION; INVIVO; HETEROGENEITY; INTERLEUKIN-2 AB Background. This study was undertaken to investigate the qualitative and quantitative changes that interstitial dendritic cells (IDC) of the heart undergo during the time course of experimental myocardial infarction. Methods and Results. Left coronary arterial ligations were performed in 43 rats that were killed 2, 4, 7, 14, and 21 days after surgery. Thirteen unoperated and 39 sham-operated rats were used as controls. Frozen sections were stained with monoclonal antibodies (OX 6 and W3/25) to identify and count IDC by light microscopy. Immunoelectron microscopy was also used to identify IDC. The number of IDC per mm2 of tissue section was calculated for all hearts. In hearts with myocardial infarction, IDC were counted in three areas: the center of the myocardial infarction, the border zone, and the noninfarcted left ventricle. In OX 6 antibody-stained preparations, the number of IDC per mm2 was 82+/-10 in the left ventricle of unoperated rats. Hearts with myocardial infarction showed marked increases in the numbers of IDC per mm2 in the border zone (796+/-79 at 7 days and 528+/-98 at 14 days). In the border zone, IDC often were associated with small clusters of T-helper lymphocytes, which reacted with W3/25 antibody (the rat homologue of human CD4). The center of the myocardial infarction showed an increase in IDC only on day 7 (120+/-18). By 21 days, IDC in the border zone were only slightly increase (159+/-15). Conclusions. These findings suggest that IDC migrate to the myocardial infarction border zone. They participate in the activation of lymphocytes and in the initiation of immune responses and decrease in number as inflammation subsides and scarring develops. C1 NHLBI,PATHOL BRANCH,ULTRASTRUCT SECT,BLDG 10,ROOM 2N240,BETHESDA,MD 20892. US FDA,DIV RES & TESTING,LAUREL,MD. NR 41 TC 39 Z9 44 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR PY 1993 VL 87 IS 3 BP 909 EP 920 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KQ923 UT WOS:A1993KQ92300023 PM 8443911 ER PT J AU PECK, CC AF PECK, CC TI CONCENTRATION-CONTROLLED VERSUS CONCENTRATION-DEFINED CLINICAL-TRIALS - REPLY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Letter ID PHENYTOIN RP PECK, CC (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 13 TC 17 Z9 17 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 1993 VL 53 IS 3 BP 385 EP 387 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KU553 UT WOS:A1993KU55300016 ER PT J AU DUARTE, CG PREUSS, HG AF DUARTE, CG PREUSS, HG TI ASSESSMENT OF RENAL-FUNCTION - GLOMERULAR AND TUBULAR SO CLINICS IN LABORATORY MEDICINE LA English DT Article RP DUARTE, CG (reprint author), US FDA,DIV CARDIORENAL DRUG PROD,5600 FISHERS LANE,ROOM 16B-45,ROCKVILLE,MD 20857, USA. NR 0 TC 39 Z9 42 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 1993 VL 13 IS 1 BP 33 EP 52 PG 20 WC Medical Laboratory Technology SC Medical Laboratory Technology GA KU022 UT WOS:A1993KU02200005 PM 8462268 ER PT J AU RUHL, S PLUZNIK, DH FELDMAN, GM AF RUHL, S PLUZNIK, DH FELDMAN, GM TI SOLUBLE INTERLEUKIN-4 RECEPTOR PRODUCTION BY MURINE MYELOID PROGENITOR CELLS - INDUCTION BY INTERLEUKIN-6 AND INTERFERON-GAMMA SO CYTOKINE LA English DT Article DE DIFFERENTIATION; INTERFERON-GAMMA; INTERLEUKIN-6; M1 CELLS; SOLUBLE INTERLEUKIN-4 RECEPTOR ID STIMULATORY FACTOR-I; MARROW-DERIVED MACROPHAGES; IL-4 RECEPTOR; ALLOREACTIVITY INVIVO; GENE-EXPRESSION; HUMAN-MONOCYTES; LYMPHOCYTES-T; HIGH-AFFINITY; IFN-GAMMA; GROWTH C1 US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. NR 40 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAR PY 1993 VL 5 IS 2 BP 144 EP 149 DI 10.1016/1043-4666(93)90053-8 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA LD406 UT WOS:A1993LD40600008 PM 8334228 ER PT J AU BINIENDA, Z BAILEY, JR DUHART, HM SLIKKER, W PAULE, MG AF BINIENDA, Z BAILEY, JR DUHART, HM SLIKKER, W PAULE, MG TI TRANSPLACENTAL PHARMACOKINETICS AND MATERNAL FETAL PLASMA-CONCENTRATIONS OF COCAINE IN PREGNANT MACAQUES NEAR TERM SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID UTERINE BLOOD-FLOW; ABUSE; DISPOSITION; EXPOSURE; SHEEP; MODEL AB The transplacental pharmacokinstics of cocaine were studied in three pregnant rhesus monkeys (Macaca mulatta) at 150-154 days of pregnancy (term approximately 165 days). Animals were dosed intramuscularly with cocaine hydrochloride at 1 mg/kg, supplemented with a tritiated cocaine tracer. Plasma cocaine and its metabolite benzoylecgonine levels were determined after separation by HPLC and subsequent quantification by liquid scintillation spectrometry. Cocaine levels peaked in maternal blood within 10-20 min after dosing, and cocaine was detected in fetal blood within 5 min, reaching peak concentrations within 30-120 min. Mean maternal elimination half-lives (t1/2) for cocaine and benzoylecgonine were 1.2 +/- 0.5 hr and 12.4 +/- 6.6 hr (+/- SEM), respectively; fetal half-lives were 0.5 +/- 0.2 and 7.7 +/- 3.0 hr. Mean maternal residence times were 1.9 +/- 0.5 and 17.0 +/- 9.1 hr for cocaine and benzoylecgonine, respectively; fetal values were 2.1 +/- 0.2 and 11.6 +/- 3.5 hr. Total areas under the concentration versus time curves (AUCs) for cocaine and benzoylecgonine in maternal plasma were 360 +/- 38 and 585 +/- 260 (ng/ml) hr, respectively; total values were 104 +/- 29 and 262 +/- 61 (ng/ml) hr. Based on AUC comparisons for cocaine, fetal exposures are thus approximately one-third of maternal exposures, demonstrating that substantial exposure to cocaine does occur in utero. RP BINIENDA, Z (reprint author), US FDA,NATL CTR TOXICOL RES,DEPT NEUROTOXICOL,NCTR DR,JEFFERSON,AR 72079, USA. FU PHS HHS [224-89-003] NR 22 TC 19 Z9 19 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 MAR-APR PY 1993 VL 21 IS 2 BP 364 EP 368 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KV611 UT WOS:A1993KV61100025 PM 8097710 ER PT J AU SANDBERG, JA MURPHEY, LJ OLSEN, GD AF SANDBERG, JA MURPHEY, LJ OLSEN, GD TI INVITRO HEPATIC BIOTRANSFORMATION OF COCAINE IN MATERNAL AND FETAL GUINEA-PIGS - INDUCTION OF COCAINE N-DEMETHYLATION WITH COCAINE PRETREATMENT SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID NORCOCAINE NITROXIDE; METABOLIZING-ENZYMES; CYTOCHROME-P-450; PREGNANCY; EXPOSURE; BINDING; STRAIN; LIVER; SEX AB In vitro N-demethylation of cocaine (COC) was examined in five saline (SAL) and five COC-treated pregnant guinea pigs and their fetuses (60 days, term 69 days). Microsomes from maternal and fetal guinea pigs produced norcocaine (NOR), benzoyinorecgonine (BN), and benzoylecgonine (BE) when incubated with COC. The initial rate of NOR formation was (mean +/- SE) 0.69 +/- 0.09 and 0.002 +/- 0.002 nmol/min/mg in microsomes from SAL-treated dams and their fetuses, respectively. The minimal fetal N-demethylation suggests BN seen previously in vivo after chronic maternal COC administration resulted from maternal formation of NOR and subsequent maternal or fetal hydrolysis to BN. COC pretreatment increased the initial rate of NOR formation to 1.38 +/- 0.28 nmol/min/mg (p < 0.05) and increased the extent of NOR formation by 12 min (p < 0.05). There was no change in total cytochrome P-450 concentrations in the dams. COC pretreatment had no effect on fetal hepatic N-demethylation of COC or total cytochrome P-450 content. The rate of NOR production plateaued in microsomes from both treatment groups by 20 min of incubation and could be restored when the microsomes were washed, repelleted, and reincubated. This suggests a soluble metabolite of COC inhibits COC N-demethylation. Microsomes from both SAL- and COC-treated animals produced this factor in the presence of COC, but the enzyme(s) responsible for COC N-demethylation in the SAL-treated pregnant guinea pig were more sensitive to inhibition than COC-pretreated animals. C1 OREGON HLTH SCI UNIV,SCH MED,DEPT PHARMACOL,L221,3181 SW SAM JACKSON PK RD,PORTLAND,OR 97201. US FDA,NATL CTR TOXICOL RES,DIV NEUROTOXICOL,PORTLAND,OR. FU NIDA NIH HHS [DA05489, DA05516, DA04905] NR 37 TC 11 Z9 11 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 MAR-APR PY 1993 VL 21 IS 2 BP 390 EP 395 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KV611 UT WOS:A1993KV61100029 PM 8097714 ER PT J AU BELAND, FA POIRIER, MC AF BELAND, FA POIRIER, MC TI SIGNIFICANCE OF DNA ADDUCT STUDIES IN ANIMAL-MODELS FOR CANCER MOLECULAR DOSIMETRY AND RISK ASSESSMENT SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID COKE-OVEN WORKERS; DOSE-RESPONSE RELATIONSHIP; WHITE BLOOD-CELLS; HEMOGLOBIN ADDUCTS; HUMAN-PLACENTA; CIGARETTE-SMOKING; HUMAN-TISSUES; HUMAN-LUNG; LIVER DNA; RAT-LIVER AB To elucidate the relationship between DNA adduct formation and tumorigenesis, a number of experiments have been conducted to measure DNA adducts in target tissues from experimental animals during continuous exposure to carcinogens. With aflatoxins, aromatic amines, and polycyclic aromatic hydrocarbons, tumor induction appears to be associated with the major DNA adduct detected, whereas with N-nitrosamines the response is normally correlated with minor forms of DNA damage. During continuous carcinogen administration, steady-state adduct concentrations are generally obtained in the target tissues, and there is often a linear correlation between the carcinogen concentration and the steady-state DNA adduct level. Exceptions exist when the mechanism of activation changes or with the onset of significant toxicity. Steady-state DNA adduct levels are often linearly related to the tumorigenic response. Carcinogen-induced cell proliferation occurs when significant deviations from linearity are observed. Because DNA adducts detected in humans are chemically identical to those found in experimental animals, DNA adduct data in animals may contribute to our understanding of human cancer risk. RP BELAND, FA (reprint author), NATL CTR TOXICOL RES, HFT-110, JEFFERSON, AR 72079 USA. NR 71 TC 37 Z9 38 U1 1 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1993 VL 99 BP 5 EP 10 DI 10.2307/3431450 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000002 PM 8319658 ER PT J AU FRIESEN, MD GARREN, L BEREZIAT, JC KADLUBAR, F LIN, DX AF FRIESEN, MD GARREN, L BEREZIAT, JC KADLUBAR, F LIN, DX TI GAS-CHROMATOGRAPHY MASS-SPECTROMETRY ANALYSIS OF 2-AMINO-1-METHYL-6-PHENYL-IMIDAZO[4,5-B]PYRIDINE IN URINE AND FECES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; MUTAGEN; FOOD; PHIP AB A method has been developed to measure levels of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) excreted in urine and feces. The method involves organic solvent extraction, derivatization to form electron-capturing bis-pentafluorobenzyl derivatives, and analysis by gas chromatography-negative ion chemical ionization mass spectrometry using a deuterium- labeled internal standard. The method can detect PhIP at levels of less than 1 ng/g in rat urine (5 ng/24 hr) and 5 ng/g (wet weight) in rat feces (50 ng/24 hr). Sprague-Dawley rats given a single 50 mug dose of PhIP by gavage excreted an average of 0.6% of the dose in the urine and 25% of the dose in the feces as unchanged PhIP, in the first 4 days after treatment. To make this method applicable for the analyses of biological fluids of PhIP-exposed human subjects, it is now being improved by using immunoaffinity chromatography. C1 NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP FRIESEN, MD (reprint author), INT AGCY RES CANC,150 COURS ALBERT THOMAS,F-69372 LYON,FRANCE. RI Friesen, Marlin/D-7328-2012 NR 5 TC 15 Z9 15 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1993 VL 99 BP 179 EP 181 DI 10.2307/3431476 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000028 PM 8319618 ER PT J AU CULP, SJ POIRIER, MC BELAND, FA AF CULP, SJ POIRIER, MC BELAND, FA TI BIPHASIC REMOVAL OF DNA ADDUCTS IN A REPETITIVE DNA-SEQUENCE AFTER DIETARY ADMINISTRATION OF 2-ACETYLAMINOFLUORENE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID RAT-LIVER; INVIVO AB Dietary administration of the hepatocarcinogen 2-acetylaminofluorene (2-AAF) to rats results in the formation of a major hepatic DNA adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF). In liver DNA, dG-C8-AF reaches steady-state conditions after approximately 2 weeks of feeding and is removed in a biphasic manner. In these experiments, we have quantified adduct concentrations in a 370 base-pair repetitive DNA fragment to determine if the adduct levels and kinetics of adduct removal were similar to those found in total genomic DNA. Male F344 rats were fed 0.02% 2-AAF for 28 days and were sacrificed at intermittent times up to 56 days after being returned to the control diet. Hepatic DNA adduct levels were measured by P-32-postlabeling or radioimmunoassay (RIA) in total genomic DNA and in a 370 base-pair fragment obtained by digesting genomic DNA with Hind III. Biphasic removal of dG-C8-AF, which composed about 90% of the total adducts measured, was observed in total genomic DNA, with comparable rate constants being detected by both P-32-postlabeling and RIA. P-32-Postlabeling also showed analogous biphasic removal of dG-C8-AF in the 370 base-pair fragment. A second adduct, 3-(deoxyguanosin-N2-yl)-2-AAF (dG-N2-AAF), which accounted for about 10% of the total adducts measured, showed similar biphasic removal kinetics in the total genomic DNA and the 370 base-pair fragment; however, as compared to dG-C8-AF, little removal of dG-N2-AAF was observed during the slow phase. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP CULP, SJ (reprint author), NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,HFT-110,JEFFERSON,AR 72079, USA. NR 9 TC 34 Z9 34 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1993 VL 99 BP 273 EP 275 DI 10.2307/3431499 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000051 PM 8319642 ER PT J AU SMITH, BA FULLERTON, NF AIDOO, A HEFLICH, RH BELAND, FA AF SMITH, BA FULLERTON, NF AIDOO, A HEFLICH, RH BELAND, FA TI DNA ADDUCT FORMATION IN RELATION TO LYMPHOCYTE MUTATIONS AND LUNG-TUMOR INDUCTION IN F344 RATS TREATED WITH THE ENVIRONMENTAL-POLLUTANT 1,6-DINITROPYRENE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID CARCINOGENICITY; BENZOPYRENE; CONDENSATE; EXHAUST; INVIVO AB Epidemiological studies suggest an association between exposure to diesel emissions and an increased incidence of lung and bladder cancer in humans. Of the compounds associated with diesel emissions, 1,6-dinitropyrene is a particularly potent mutagen and carcinogen. In these experiments we administered [4,5,9,10-H-3]1,6-dinitropyrene (30 or 100 mug) directly to the lungs of F344 rats according to a protocol known to induce lung tumors and characterized the DNA adducts present in the target tissue. In addition, we examined the adducts present in spleen lymphocytes and assayed for the induction of mutations at the hypoxanthine-guanine phosphoribosyltransferase locus in these cells as measured by the frequency of 6-thioguanine-resistant (TG(r)) T-lymphocytes. Adduct formation was detected in both lung and spleen lymphocyte DNA, with the extent of binding being dose-dependent in the lymphocytes but not the lung. P-32-Postlabeling analyses indicated the formation of a major DNA adduct, N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene, in both tissues. 1,6-Dinitropyrene treatment resulted in a dose-dependent increase in TG(r) T-lymphocytes, with the increase being detected for at least 21 weeks after treatment. These data indicate that 1,6-dinitropyrene is metabolically activated by nitroreduction to form DNA adducts in both the target tissue and spleen lymphocytes and that a tumorigenic dose results in a significant induction of TG(r) T-lymphocytes. C1 NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,HFT-110,JEFFERSON,AR 72079. NATL CTR TOXICOL RES,DIV GENET TOXICOL,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOLEC BIOL,LITTLE ROCK,AR 72205. NR 15 TC 7 Z9 7 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1993 VL 99 BP 277 EP 280 DI 10.2307/3431500 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000052 PM 8319643 ER PT J AU TALASKA, G SCHAMER, M SKIPPER, P TANNENBAUM, S CAPORASO, N KADLUBAR, F BARTSCH, H VINEIS, P AF TALASKA, G SCHAMER, M SKIPPER, P TANNENBAUM, S CAPORASO, N KADLUBAR, F BARTSCH, H VINEIS, P TI CARCINOGEN-DNA ADDUCTS IN EXFOLIATED UROTHELIAL CELLS - TECHNIQUES FOR NONINVASIVE HUMAN MONITORING SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT CONF ON BIOMONITORING AND SUSCEPTIBILITY MARKERS IN HUMAN CANCER : APPLICATIONS IN MOLECULAR EPIDEMIOLOGY AND RISK ASSESSMENT CY OCT 26-NOV 01, 1991 CL KAILUA KONA, HI SP INT AGCY RES CANC, NATL CTR TOXICOL RES, US EPA, COMMISS EUROPEAN COMMUNITIES, NATL CANC INST ID HEMOGLOBIN ADDUCTS; CIGARETTE-SMOKING; PHENOTYPE AB Detection of carcinogen-DNA adducts m DNA from exfoliated urothelial cells from animals and humans exposed to potential environmental carcinogens is described. In an animal model, 4-aminobiphenyl-DNA adducts were detected, and the shape of the dose-response curve was related to the levels of 4-aminobiphenyl-hemoglobin adducts. In a human study, five distinct adducts were two to nine times higher in smokers than in nonsmokers. The association of four adduct measures with smoking was corroborated by significant correlations with levels of 4-aminobiphenyl-hemoglobin adducts, type and number of cigarettes smoked, and/or urinary mutagenicity. One adduct seemed chromatographically similar to N-(deoxyguanosin-8-yl)-4-aminobiphenyl. This adduct showed the strongest correlation with 4-aminobiphenyl-hemoglobin adduct levels. These data suggest that noninvasive techniques can be applied to the study of carcinogen-DNA adducts in the target organ of humans at risk for urinary bladder cancer. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. MIT,DIV TOXICOL,CAMBRIDGE,MA 02139. NCI,FAMILY STUDIES SECT,BETHESDA,MD 20892. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. INT AGCY RES CANC,F-69372 LYON,FRANCE. RP TALASKA, G (reprint author), UNIV CINCINNATI,INST ENVIRONM HLTH ML056,CINCINNATI,OH 45267, USA. NR 12 TC 30 Z9 30 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1993 VL 99 BP 289 EP 291 DI 10.2307/3431503 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LC430 UT WOS:A1993LC43000055 PM 8319646 ER PT J AU COLLINS, TFX BLACK, TN ODONNELL, MW SHACKELFORD, ME BULHACK, P AF COLLINS, TFX BLACK, TN ODONNELL, MW SHACKELFORD, ME BULHACK, P TI TERATOGENIC POTENTIAL OF FD-AND-C RED NO-3 WHEN GIVEN IN DRINKING-WATER SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID LIFETIME TOXICITY CARCINOGENICITY; ERYTHROSINE; RATS AB FD & C Red No. 3 (erythrosine), a commonly used food additive, was administered to pregnant Osborne-Mendel rats to study its teratogenic potential. Dosing solutions of 0.05, 0.1, 0.2 or 0.4% in distilled water were available at all times and corresponded to daily doses of 64, 121, 248 and 472 mg FD & C Red No. 3/kg body weight. Distilled water served as the control. On gestation day 20, the animals were killed and caesarean sections were performed. The treated animals consumed less fluid than did the control animals, but only random decreases were statistically significant and no dose relationship was seen. Only the 0.2% group consumed significantly more feed than the controls during gestation. Maternal weight gain during days 0-20 was not significantly affected in any group. No dose-related changes were seen in maternal clinical findings, implantations, foetal viability, foetal size (weight and length) or visceral development. No dose-related teratogenesis was seen. Skeletal development was not affected; the few statistically significant increases in skeletal variations were not dose related and were considered to be random. FD & C Red No. 3 was neither foetotoxic nor teratogenic at the dose levels tested in drinking water. RP COLLINS, TFX (reprint author), US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204, USA. NR 18 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAR PY 1993 VL 31 IS 3 BP 161 EP 167 DI 10.1016/0278-6915(93)90089-H PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA KZ593 UT WOS:A1993KZ59300001 PM 8386132 ER PT J AU NAIR, J ROUSE, DA MORRIS, SL AF NAIR, J ROUSE, DA MORRIS, SL TI NUCLEOTIDE-SEQUENCE ANALYSIS AND SEROLOGIC CHARACTERIZATION OF A 27-KILODALTON MYCOBACTERIUM-INTRACELLULARE LIPOPROTEIN SO INFECTION AND IMMUNITY LA English DT Article ID AVIUM COMPLEX INFECTION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INTEGRAL MEMBRANE-PROTEINS; IMMUNE-DEFICIENCY SYNDROME; POLYMERASE CHAIN-REACTION; ESCHERICHIA-COLI; TUBERCULOSIS; ANTIGENS; ANTIBODY; IDENTIFICATION AB Disseminated mycobacteremia resulting from Mycobacterium avium-Mycobacterium intracellulare complex (MAC) infections frequently contribute to the morbidity and mortality seen in AIDS patients. To better understand the immunopathology of MAC disease and to identify molecules that may have potential diagnostic and vaccine utility, an immunoreactive M. intracellulare protein (MI43) and the gene encoding this antigen were characterized. Southern blot hybridizations demonstrated that MI43 gene probes reacted only with genomic DNA from M. intracellulare, M. avium, and Mycobacterium asiaticum and not with DNA isolated from 11 other mycobacterial species. Nucleotide sequence analysis showed that the MI43 gene encodes a 27-kDa protein which contains a consensus bacterial lipoprotein processing sequence. Detergent-phase separations and metabolic labeling with [H-3]palmitate also suggested that MI43 is a lipoprotein. Serological assays demonstrated that recombinant MI43 fusion proteins react with sera from M. avium-infected mice, sera from patients with NIAC disease, and sera from patients with active tuberculosis. These results further suggest that mycobacterial lipoproteins are important immunogens that should be considered in the development of improved mycobacterial vaccines and diagnostic reagents. C1 US FDA,CTR BIOL EVALUAT & RES,MYCOBACTERIA LAB,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 45 TC 12 Z9 13 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 MAR PY 1993 VL 61 IS 3 BP 1074 EP 1081 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KN097 UT WOS:A1993KN09700039 PM 8432589 ER PT J AU NATARO, JP DENG, YK GIRON, JA SAVARINO, SJ KOTHARY, MH HALL, R AF NATARO, JP DENG, YK GIRON, JA SAVARINO, SJ KOTHARY, MH HALL, R TI AGGREGATIVE ADHERENCE FIMBRIA-I EXPRESSION IN ENTEROAGGREGATIVE ESCHERICHIA-COLI REQUIRES 2 UNLINKED PLASMID REGIONS SO INFECTION AND IMMUNITY LA English DT Note ID PERSISTENT DIARRHEA; REGULATORY GENE; HEP-2 CELLS; PATTERNS; RNS; ASSOCIATION; STRAINS; CLONING; CFA/I AB Adherence to HEp-2 cells by many enteroaggregative Escherichia coli (EAggEC) strains is associated with the expression of flexible, bundle-forming fimbriae 2 to 3 nm in diameter, designated aggregative adherence fimbriae I (AAF/I). We have previously reported the molecular cloning and TnphoA mutagenesis of AAF/I genes from the large plasmid of prototype EAggEC strain 17-2 (J. P. Nataro, Y. Deng, D. R. Maneval, A. L. German, W. C. Martin, and M. M. Levine, Infect. Immun. 60:2297-2304, 1992). Here, we report that further mapping and subcloning of AAF/I regions suggest that expression of the fimbriae requires two separate plasmid regions (designated regions 1 and 2). Approximately 9 kb of DNA unnecessary for fimbrial expression separates the two regions; this intervening segment encodes the EAggEC heat-stable enterotoxin (EAST1). Neither region was capable of conferring aggregative HEp-2 adherence (AA) when cloned individually; when the two regions were cloned as a single fragment or when each was cloned into a different vector and introduced into the same E. coli HB101 cell, AA was restored. AA-positive constructs also expressed human erythrocyte hemagglutination, autoagglutination in broth cultures, and the production of AAF/I as detected by immunogold electron microscopy. C1 USN,MED RES INST,ENTER DIS PROGRAM,BETHESDA,MD 20889. US FDA,CTR FOOD SAFETY & APPL NUTR,DIV MICROBIOL,VIRULENCE ASSESSMENT BRANCH,WASHINGTON,DC 20204. RP NATARO, JP (reprint author), UNIV MARYLAND,SCH MED,DEPT PEDIAT & MED,CTR VACCINE DEV,BALTIMORE,MD 21201, USA. FU NIAID NIH HHS [1R29-AI-33096, N01-AI-15096] NR 26 TC 68 Z9 68 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 MAR PY 1993 VL 61 IS 3 BP 1126 EP 1131 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KN097 UT WOS:A1993KN09700047 PM 8094379 ER PT J AU HOLCOMB, M SUTHERLAND, JB CHIARELLI, MP KORFMACHER, WA THOMPSON, HC LAY, JO HANKINS, LJ CERNIGLIA, CE AF HOLCOMB, M SUTHERLAND, JB CHIARELLI, MP KORFMACHER, WA THOMPSON, HC LAY, JO HANKINS, LJ CERNIGLIA, CE TI HPLC AND FAB MASS-SPECTROMETRY ANALYSIS OF FUMONISINS B1 AND B2 PRODUCED BY FUSARIUM-MONILIFORME ON FOOD SUBSTRATES SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article ID LEUKOENCEPHALOMALACIA; TOXICITY; CANCER; HORSES; RATS AB Flasks containing moistened, autoclaved corn, unmilled rice, peanuts, soybeans, and laboratory rodent feed were inoculated with Fusarium moniliforme NRRL 13616 and incubated in the dark at 25-degrees-C. After 24 days, the cultures were extracted with acetonitrile and water. High-performance liquid chromatography (HPLC) of the extracts, after they had been derivatized with fluorescamine, showed high concentrations of fumonisins B1 and B2 (10 242 and 3068 mug/g, respectively) in the corn cultures and moderately high concentrations (206 and 100 mug/g, respectively) in the unmilled rice cultures. HPLC also detected fumonisins B1 and B2 (34 and 50 mug/g, respectively) in the rodent feed cultures. Only trace levels (5 mug/g or less) of fumonisin B1 were detected in the peanut and soybean cultures. Fast atom bombardment mass spectrometry (FAB MS) confirmed the presence of fumonisins B1 and B2 in the corn, unmilled rice, and rodent feed cultures. C1 UNIV ARKANSAS,LITTLE ROCK,AR 72204. RP HOLCOMB, M (reprint author), US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079, USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 18 TC 37 Z9 39 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR PY 1993 VL 41 IS 3 BP 357 EP 360 DI 10.1021/jf00027a004 PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA KT439 UT WOS:A1993KT43900004 ER PT J AU POTHULURI, JV FREEMAN, JP EVANS, FE MOORMAN, TB CERIGLIA, CE AF POTHULURI, JV FREEMAN, JP EVANS, FE MOORMAN, TB CERIGLIA, CE TI METABOLISM OF ALACHLOR BY THE FUNGUS CUNNINGHAMELLA-ELEGANS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article ID LIVER MICROSOMAL-ENZYMES; CHAETOMIUM-GLOBOSUM; INVITRO OXIDATION; ARYL ACYLAMIDASE; GROUND-WATER; SOIL FUNGUS; FORMALDEHYDE; DEGRADATION; HERBICIDES; 2,6-DIETHYLANILINE AB The fungus Cunninghamella elegans ATCC 36112 transformed 98.6% of [C-14]alachlor [2-chloro-N-methoxymethyl-N-(2,6-diethylphenyl)acetamide] added to Sabouraud's dextrose broth to four metabolites within 96 h. Metabolism occurred predominantly by benzylic hydroxylation of one of the arylethyl side chains. Metabolites were separated by reversed-phase high-performance liquid chromatography and identified by H-1 nuclear magnetic resonance, UV, and mass spectral techniques. Two major metabolites were isomers of 2-chloro-N-(methoxymethyl)-N-[2-ethyl-6-(l-hydroxyethyl)-phenyl]acetamide and another was 2-chloro-N-(2,6-diethylphenyl)acetamide; the minor metabolite was 2-chloro-N-(methoxymethyl)-N-(2-vinyl-6-ethylphenyl)acetamide. The fungal transformations appear to be similar to those of mammalian microsomal oxidation since C. elegans oxidized alachlor at the benzylic positions and N-dealkylation occurred. C1 US FDA,NATL CTR TOXICOL RES,JEFFERSON,AR 72079. USDA ARS,NATL SOIL TILTH LAB,AMES,IA 50011. NR 42 TC 19 Z9 20 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR PY 1993 VL 41 IS 3 BP 483 EP 488 DI 10.1021/jf00027a026 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA KT439 UT WOS:A1993KT43900026 ER PT J AU SCHER, AL ADAMO, NC AF SCHER, AL ADAMO, NC TI LIQUID-CHROMATOGRAPHIC DETERMINATION OF 2-CHLORO-4-NITROANILINE, 2-NAPHTHOL, AND 2,4-DINITROANILINE IN D-AND-C RED NO 36 SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A method is described for the determination of the intermediates and a related impurity in D&C Red No. 36 by reversed-phase liquid chromatography. This method may be used to ensure that limits set forth in the Code of Federal Regulations on the amounts of these 3 impurities in the color are not exceeded. The pigment is dissolved in boiling dioxane and then precipitated. The filtrate is chromatographed by isocratic elution, and then the column is washed and reequilibrated. Impurities were identified as 2-chloro-4-nitroaniline (2-Cl-4-NA), 2-naphthol, and 2,4-dinitroaniline (2,4-DNA) by comparison of their retention times and spectra with those of standards. Peak area calibrations were linear to at least 0.375% 2-Cl-4-NA, 1.25% 2-naphthol, and 0.025% 2,4-DNA, all with zero intercepts. At the specification levels, 99% confidence limits were 0.30 +/- 0.006% for 2-Cl-4-NA, 1.0 +/- 0.03% for 2-naphthol, and 0.020 +/- 0.0004% for 2,4-DNA. The limits of determination calculated from calibration data were 0.019% for 2-Cl-4-NA, 0.10% for 2-naphthol, and 0.001 4% for 2,4-DNA at the 99% confidence level. Recoveries were 100-1 04% for 2-Cl-4-NA added to purified D&C Red No. 36, 100% for 2-naphthol, and 100-110% for 2,4-DNA; relative standard deviations were 0.8-3.4%. A survey of certified D&C Red No. 36 samples showed that the batches contained higher levels of intermediates than were determined previously by a cellulose column method in which the pigment was not dissolved. RP SCHER, AL (reprint author), US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204, USA. NR 6 TC 3 Z9 3 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1993 VL 76 IS 2 BP 287 EP 291 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA KT990 UT WOS:A1993KT99000006 PM 8471855 ER EF