FN Thomson Reuters Web of Science™ VR 1.0 PT J AU MENENDEZARIAS, L YOUNG, M OROSZLAN, S AF MENENDEZARIAS, L YOUNG, M OROSZLAN, S TI PURIFICATION AND CHARACTERIZATION OF THE MOUSE MAMMARY-TUMOR VIRUS PROTEASE EXPRESSED IN ESCHERICHIA-COLI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GLUTATHIONE-S-TRANSFERASE; DEFICIENCY SYNDROME AIDS; CELL LEUKEMIA-VIRUS; HIV-1 PROTEASE; NUCLEOTIDE-SEQUENCE; ASPARTIC PROTEASE; CRYSTAL-STRUCTURE; PROTEINS; GAG AB The mouse mammary tumor virus (MMTV) protease gene was cloned into pGEX-2T, an Escherichia coli expression vector containing the glutathione S-transferase coding region of Schistosoma japonicum. The chimeric protein was formed by fusion of the glutathione S-transferase with a hexapeptide which contains a thrombin cleavage site, followed by the MMTV protease. Affinity chromatography on a glutathione-Sepharose 4B column was used to isolate the chimeric protein. After thrombin cleavage, the glutathione S-transferase and the protease were separated by gel filtration chromatography on a Sephadex G-75 column. The overall yield of the protease purification procedure was about 1 mg of protease/liter of culture, and the specific activity was 380 pmol/min.mug of enzyme. Like other retroviral proteases, the MMTV enzyme was active as a dimer, showed maximum activity at pH between 4 and 6, and could be inhibited by pepstatin A and a phosphinic acid derivative HIV-1 protease inhibitor. Enzymatic characterization of this protease reveals its broad specificity, showing a clear preference for the oligopeptide substrate mimicking the cleavage site at the amino-terminal end of the capsid protein (k(cat)/K(m) = 9725.5 M-1.s-1). The chimeric protein was also an active dimer and showed a similar K(m) (17 muM) for such an oligopeptide, although its k(cat) was about 10 times smaller. Autocatalytic processing of the MMTV protease was observed after expression of clones containing the natural cleavage site, as it occurs at the amino-terminal end of the viral protease, instead of the thrombin-sensitive sequence. RP MENENDEZARIAS, L (reprint author), NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOLEC VIROL & CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. RI Menendez Arias, Luis /G-2436-2016; Menendez Arias, Luis/N-7447-2016 OI Menendez Arias, Luis/0000-0002-1251-6640 FU NCI NIH HHS [N01-CO-74101] NR 40 TC 27 Z9 31 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 24134 EP 24139 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900105 PM 1331110 ER PT J AU DIXON, KH MULLIGAN, T CHUNG, KN ELWOOD, PC COWAN, KH AF DIXON, KH MULLIGAN, T CHUNG, KN ELWOOD, PC COWAN, KH TI EFFECTS OF FOLATE RECEPTOR EXPRESSION FOLLOWING STABLE TRANSFECTION INTO WILD-TYPE AND METHOTREXATE TRANSPORT-DEFICIENT ZR-75-1 HUMAN BREAST-CANCER CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN KB-CELLS; PROBENECID-SENSITIVE CARRIER; AMINO-ACID-SEQUENCE; CCRF-CEM CELLS; BINDING-PROTEIN; L1210 CELLS; GLYCOSYL-PHOSPHATIDYLINOSITOL; LEUKEMIA-CELLS; OVARIAN-CANCER; HUMAN-PLACENTA AB Two biochemically distinct systems, the high affinity folate receptor and the lower affinity reduced-folate carrier, have each been implicated in mediating the transport of folates and antifolates into cells. Previous studies from our laboratory have shown that methotrexate accumulation into wild type (WT) ZR-75-1 human breast cancer cells involves a system with characteristics of the reduced-folate carrier, that this system is deficient in methotrexate resistant (MTX(R)) ZR-75-1 cells in which methotrexate transport is undetectable and that neither breast cancer cell line expresses folate receptors. In this report we examined the possible interaction of the reduced-folate carrier with folate receptors by stably transfecting both WT ZR-75-1 and MTX(R) ZR-75-1 cells with an expression vector containing a folate receptor cDNA. Clones of stably transfected MTX(R) ZR-75-1 and WT ZR-75-1 cells expressing comparable levels of folate receptors were studied and compared to the nontransfected cell lines. Although nontransfected WT and MTX(R) ZR-751 cell lines require concentrations greater-than-or-equal-to 100 nM folic acid for growth, the expression of folate receptors in transfected WT and MTX(R) ZR-75-1 cells permitted the growth of both cell lines in low concentrations (1 nM) of folic acid. While the defect in the reduced-folate carrier system in MTX(R) ZR-75-1 cells inhibits their growth in medium containing low concentrations of folinic acid (less-than-or-equal-to 1 muM), MTX(R) ZR-75-1 cells expressing folate receptors display uninhibited growth in 1 nM folinic acid. The accumulation of folic acid, folinic acid, and methotrexate is enhanced in folate receptor-transfected WT ZR-75-1 cells and MTX(R) ZR-75-1 cells. Furthermore, the accumulation of folates and antifolate was similar in both transfected WT and MTX(R) ZR751 cell lines that expressed folate receptors. This suggests that alterations in the reduced-folate carrier do not affect folate receptor function. We also examined the effect of folate receptor expression on the sensitivity of WT and MTX(R) ZR-75-1 cells to methotrexate and to the lipophillic antifolate trimetrexate. Increased folate receptor expression decreased the sensitivity of WT ZR-75-1 cells toward the antifolate trimetrexate, presumably through increased uptake of reduced folates. Although the expression of the folate receptor enhanced the growth of both cell lines in low folate concentrations, it did not affect the sensitivity of either WT or MTX(R) ZR-75-1 cells to methotrexate. RP DIXON, KH (reprint author), NCI,MED BRANCH,BLDG 10,RM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 57 TC 50 Z9 50 U1 0 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 NOV 25 PY 1992 VL 267 IS 33 BP 24140 EP 24147 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900106 PM 1429743 ER PT J AU JUVONEN, RO IWASAKI, M NEGISHI, M AF JUVONEN, RO IWASAKI, M NEGISHI, M TI ROLES OF RESIDUE-129 AND RESIDUE-209 IN THE ALTERATION BY CYTOCHROME-B5 OF HYDROXYLASE-ACTIVITIES IN MOUSE-2A-P450S SO BIOCHEMISTRY LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; SITE-DIRECTED MUTAGENESIS; AFFINITY-CHROMATOGRAPHY; COUMARIN 7-HYDROXYLASE; PHOSPHORYLATION; SUBSTRATE; RAT; IDENTIFICATION; REDUCTASE; OXIDATION AB Cytochrome b5 stimulates the coumarin 7-hydroxylation activity of P450coh. A mutation of Arg-129 in P450coh, however, abolishes the stimulation. Moreover, this mutant P450coh binds loosely to cytochrome b5-conjugated Sepharose 4B, whereas wild-type P450coh binds tightly. Consistent with this, the mutation increases the K(a) value for b5 binding approximately 6-fold. The identity of residue 209 also alters the stimulation of the activity of P450coh depending on the type of the substrates used and products formed. Coumarin 7-hydroxylation activity is greatly stimulated by cytochrome b5 only when Phe is at position 209, while cytochrome b5 stimulates testosterone hydroxylation activity of P450coh in which Phe, Asn, Ser or Lys substitutes residue 209. P450coh changes its rate of hydrogen peroxide formation depending on the identity of residue 209 and substrate used. Cytochrome b5 decreases the hydrogen peroxide formation of some P450coh whose activities are stimulated by the cytochrome; however, the decrease does not always result in stimulating the activity. The results indicate, therefore, that residues 129 and 209 play different roles in stimulating P450coh activity by cytochrome b5; Arg-129 is a key residue in the cytochrome b5-binding domain and is essential for the stimulation. Residue 209, however, alters the efficiency of electron transport for substrate oxidation as a residue which resides near the sixth ligand of heme and in the substrate-binding site. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,RES TRIANGLE PK,NC 27709. NR 35 TC 29 Z9 30 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 NOV 24 PY 1992 VL 31 IS 46 BP 11519 EP 11523 DI 10.1021/bi00161a033 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ523 UT WOS:A1992JZ52300033 PM 1445886 ER PT J AU HAYES, JJ CLEMENS, KR AF HAYES, JJ CLEMENS, KR TI LOCATIONS OF CONTACTS BETWEEN INDIVIDUAL ZINC FINGERS OF XENOPUS-LAEVIS TRANSCRIPTION FACTOR-IIIA AND THE INTERNAL CONTROL REGION OF A 5S RNA GENE SO BIOCHEMISTRY LA English DT Article ID DNA RECOGNITION; 5S-RNA GENE; BINDING; PROTEIN; DOMAINS; COMPLEX; TFIIIA; MODEL AB A set of mutants of transcription factor IIIA (TFIIIA) have been prepared in which successive zinc-finger domains have been deleted from the carboxyl terminus of the protein. These have been analyzed by hydroxyl radical footprinting to map the location of contacts to DNA by individual zinc-finger domains of TFIIIA. The results suggest that the nine zinc fingers of TFIIIA are organized into three DNA-binding domains of three fingers each. The spatial relationship between zinc-finger contacts to 5S DNA suggests that the two domains which interact with either end of the DNA-binding site of TFIIIA (fingers 1-3 and 7-9) have a compact conformation, similar to that exemplified by the zif268 cocrystal structure [Pavletich, N. P., & Pabo, C. O. (1991) Science 252, 809-817]. However, the central domain (fingers 4-6) has a much more extended conformation, following a path nearly parallel to the helix axis and contacting over 20 base pairs of DNA in the center of the binding site of TFIIIA. These results strongly support two recently proposed and radically new models for the TFIIIA/5S DNA complex [Hayes, J. J., & Tullius, T. D. (1992) J. Mol. Biol. 227,407-417; Clemens, K. R., Liao, X., Wolf, V., Wright, P. E., & Gottesfeld, J. M. (1992) Proc. Natl. Acad. Sci. U.S.A. (in press)]. C1 SCRIPPS RES INST, DEPT MOLEC, LA JOLLA, CA 92037 USA. RP HAYES, JJ (reprint author), NICHHD, MOLEC EMBRYOL LAB, BETHESDA, MD 20892 USA. FU NCI NIH HHS [F32 CA09023] NR 25 TC 43 Z9 43 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 NOV 24 PY 1992 VL 31 IS 46 BP 11600 EP 11605 DI 10.1021/bi00161a045 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ523 UT WOS:A1992JZ52300045 PM 1332765 ER PT J AU LYON, MJ AGRANOFF, BW SOKOLOFF, L SMITH, CB AF LYON, MJ AGRANOFF, BW SOKOLOFF, L SMITH, CB TI RESIDUAL EFFECTS OF TRACER IN SEQUENTIAL DOUBLE LABEL DEOXYGLUCOSE STUDIES SO NEUROSCIENCE LETTERS LA English DT Article DE DEOXYGLUCOSE; DOUBLE LABEL AUTORADIOGRAPHY; ENERGY METABOLISM; BRAIN; CNS ID CEREBRAL GLUCOSE-UTILIZATION; 2-DEOXYGLUCOSE; RAT AB The validity of sequential double label deoxyglucose (DG) determinations of local metabolic rate for glucose (IMR(glc)) was examined by quantifying the degree of trapping of residual first DG tracer during the second experimental period. One sciatic nerve was repetitively stimulate for 25 min, beginning either at the time of the DG injection or 25 min later. IMR(glc) in the ipsilateral dorsal horn of the lumbar spinal cord was found to be 105% and 56%, respectively. greater than that of the contralateral unstimulated side. Attempts to lower the body burden of radioactive DG by exchange blood transfusion failed to reduce this delayed effect. These data indicate that residual effects of the first tracer could obscure possible differences in IMR(glc) between two sequential experimental states. C1 NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. SUNY HLTH SCI CTR,DEPT OTOLARYNGOL,SYRACUSE,NY. UNIV MICHIGAN,MENTAL HLTH RES INST,NEUROSCI LAB,ANN ARBOR,MI 48109. NR 16 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 23 PY 1992 VL 147 IS 1 BP 72 EP 76 DI 10.1016/0304-3940(92)90777-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA KB352 UT WOS:A1992KB35200018 PM 1480326 ER PT J AU SMITH, CD CARNEY, JM TATSUMO, T STADTMAN, ER FLOYD, RA MARKESBERY, WR AF SMITH, CD CARNEY, JM TATSUMO, T STADTMAN, ER FLOYD, RA MARKESBERY, WR TI PROTEIN OXIDATION IN AGING BRAIN SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID MIXED-FUNCTION OXIDATION; GLUTAMINE-SYNTHETASE; ESCHERICHIA-COLI; CYSTEINE PROTEINASE; ALZHEIMERS-DISEASE; OXYGEN RADICALS; DEGRADATION; INACTIVATION; TURNOVER; DAMAGE C1 UNIV KENTUCKY,MED CTR,DEPT PHARMACOL,LEXINGTON,KY 40536. UNIV KENTUCKY,MED CTR,DEPT PATHOL,LEXINGTON,KY 40536. UNIV KENTUCKY,MED CTR,SANDERS BROWN CTR AGING,LEXINGTON,KY 40536. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. OKLAHOMA MED RES FDN,MOLEC TOXICOL RES GRP,OKLAHOMA CITY,OK 73104. RP SMITH, CD (reprint author), UNIV KENTUCKY,MED CTR,DEPT NEUROL,800 ROSE ST,MS-129,LEXINGTON,KY 40536, USA. FU NIA NIH HHS [1P50-AG055144, 1PO1-AG05119]; NINDS NIH HHS [1KO8 NS01421-01] NR 57 TC 100 Z9 104 U1 1 U2 4 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 NOV 21 PY 1992 VL 663 BP 110 EP 119 DI 10.1111/j.1749-6632.1992.tb38654.x PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KJ581 UT WOS:A1992KJ58100013 PM 1362341 ER PT J AU FORNACE, AJ JACKMAN, J HOLLANDER, MC HOFFMANLIEBERMANN, B LIEBERMANN, DA AF FORNACE, AJ JACKMAN, J HOLLANDER, MC HOFFMANLIEBERMANN, B LIEBERMANN, DA TI GENOTOXIC-STRESS-RESPONSE GENES AND GROWTH-ARREST GENES - GADD, MYD, AND OTHER GENES INDUCED BY TREATMENTS ELICITING GROWTH ARREST SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID STIMULATORY FACTOR-II; DNA-DAMAGING AGENTS; CELL-CYCLE RESPONSE; SACCHAROMYCES-CEREVISIAE; MAMMALIAN-CELLS; UV-IRRADIATION; MYELOID CELLS; DIFFERENTIATION; INDUCTION; INTERLEUKIN-6 C1 UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. RP FORNACE, AJ (reprint author), NCI,DTP,MOLEC PHARMACOL LAB,ROOM 5C09,BLDG 37,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 42 TC 156 Z9 156 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 NOV 21 PY 1992 VL 663 BP 139 EP 153 DI 10.1111/j.1749-6632.1992.tb38657.x PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KJ581 UT WOS:A1992KJ58100016 PM 1482047 ER PT J AU ARAI, M ARAI, R KANI, K JACOBOWITZ, DM AF ARAI, M ARAI, R KANI, K JACOBOWITZ, DM TI IMMUNOHISTOCHEMICAL LOCALIZATION OF CALRETININ IN THE RAT LATERAL GENICULATE-NUCLEUS AND ITS RETINOGENICULATE PROJECTION SO BRAIN RESEARCH LA English DT Article DE CALRETININ; CALCIUM-BINDING PROTEIN; LATERAL GENICULATE NUCLEUS; RETINOGENICULATE PROJECTION; IMMUNOHISTOCHEMISTRY; EYE ENUCLEATION; RAT ID CALCIUM-BINDING PROTEIN; CENTRAL NERVOUS-SYSTEM; IMMUNOCYTOCHEMICAL LOCALIZATION; CONTAINING NEURONS; GANGLION-CELLS; ALBINO-RATS; ORGANIZATION; BRAIN; IMMUNOREACTIVITY; DORSAL AB In the present study, we examined the distribution of calretinin-immunoreactive neuronal cell bodies and fibers in the lateral geniculate nucleus of the rat. In normal rats, clusters of immunoreactive cell bodies were found in: (i) the rostral portion of the ventral lateral geniculate nucleus pars medialis (VLGM), (ii) the intergeniculate leaflet (IGL), (iii) the intermediate region between the VLGM and the ventral lateral geniculate nucleus pars lateralis (VLGL), (iv) the caudomedial portion of the VLGM, and (v) the caudolateral portion of the VLGM. In the dorsal lateral geniculate nucleus (DLG), immunoreactive cell bodies were rarely observed. After uni- or bilateral eye enucleation, no significant alteration in the morphological features or distribution of immunoreactive cell bodies was detected in the lateral geniculate nucleus. In normal rats, immunoreactive fibers formed dense plexuses in: (i) the DLG, (ii) the external layer of the VLGL, (iii) the internal layer of the VLGL, (iv) the IGL, (v) the caudomedial portion of the VLGM, and (vi) the optic tract. After unilateral eye enucleation, immunoreactive fibers in the external layer of the VLGL and in the optic tract almost totally disappeared on the contralateral side to the lesion. Unilateral eye enucleation caused a significant decrease of immunoreactive fibers in the DLG and in the internal layer of the VLGL, but a substantial number of immunoreactive fibers still remained there. In the IGL and the caudomedial portion of the VLGM, no observable alteration in the distribution of immunoreactive fibers was detected after uni- or bilateral eye enucleation. In conclusion, (i) subpopulations of neurons of the lateral geniculate nucleus are distinguished by the presence of calretinin immunoreactivity, and (ii) calretinin is a chemical component of subpopulations of the contralateral retino-geniculate pathway, which terminate in the DLG and in the external and internal layers of the VLGL. C1 FUJITA HLTH UNIV,SCH MED,DEPT ANAT,AICHI,JAPAN. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP ARAI, M (reprint author), SHIGA UNIV MED SCI,DEPT OPHTHALMOL,OTSU,SHIGA 52021,JAPAN. NR 42 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 20 PY 1992 VL 596 IS 1-2 BP 215 EP 222 DI 10.1016/0006-8993(92)91550-X PG 8 WC Neurosciences SC Neurosciences & Neurology GA JZ907 UT WOS:A1992JZ90700026 PM 1467985 ER PT J AU AANONSEN, LM KAJANDER, KC BENNETT, GJ SEYBOLD, VS AF AANONSEN, LM KAJANDER, KC BENNETT, GJ SEYBOLD, VS TI AUTORADIOGRAPHIC ANALYSIS OF I-125 SUBSTANCE-P BINDING IN RAT SPINAL-CORD FOLLOWING CHRONIC CONSTRICTION INJURY OF THE SCIATIC-NERVE SO BRAIN RESEARCH LA English DT Article DE CHRONIC CONSTRICTION INJURY; PAIN; HYPERALGESIA; RECEPTOR BINDING; AUTORADIOGRAPHY; SUBSTANCE-P; SPINAL CORD; NK1 RECEPTOR ID PRIMARY SENSORY NEURONS; SUBSTANCE-P BINDING; PRIMARY AFFERENT TERMINALS; SUPERFICIAL DORSAL HORN; A GENE-EXPRESSION; PERIPHERAL MONONEUROPATHY; ANTIBODY MICROPROBES; SPINOTHALAMIC TRACT; PAIN; RELEASE AB Using receptor binding and autoradiographic techniques, changes in Bolton-Hunter labeled I-125-substance P (I-125-BH-SP) binding were determined in laminae I/II, V and X of rat lumbar spinal cord after chronic constriction injury (CCI) of the sciatic nerve. When compared to the sham-operated side of the control group, SP binding significantly increased ipsilateral to the CCI in laminae I/II at 5, 10 and 20 days after injury and in lamina V at 5 days after injury. Scatchard analysis was performed on the I-125-BH-SP binding to the NK1 receptor in laminae I/II of rats 5 days after generation of the CCI. A significant decrease in the K(d) of I-125-BH-SP binding was observed in laminae I/II ipsilateral to CCI when compared with the control side (ipsilateral to sham surgery). There was no significant change in the B(max) in laminae I/II ipsilateral to CCI. The changes in I-125-BH-SP binding in the rat spinal cord that occurred after CCI were found in areas of the spinal cord that receive terminations of nociceptive primary afferent fibers. The increased affinity of the NK1 binding site that we report could result in an increase in SP receptor activation in laminae I/II. Such central changes in SP binding may contribute to the neuropathic pain syndrome observed in rats with the CCI. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455. FU NIDA NIH HHS [DA05309]; NINDS NIH HHS [NS17702] NR 63 TC 41 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 20 PY 1992 VL 596 IS 1-2 BP 259 EP 268 DI 10.1016/0006-8993(92)91556-T PG 10 WC Neurosciences SC Neurosciences & Neurology GA JZ907 UT WOS:A1992JZ90700032 PM 1281746 ER PT J AU ITO, Y SHIBUSAWA, Y FALES, HM CAHNMANN, HJ AF ITO, Y SHIBUSAWA, Y FALES, HM CAHNMANN, HJ TI STUDIES ON AN ABNORMALLY SHARPENED ELUTION PEAK OBSERVED IN COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY LA English DT Article AB Counter-current chromatography (CCC) of the bromoacetylation product of 3,3',5-triiodo-L-thyronine (T3) produced an unusually sharp peak for the desired product, N-bromoacetyl T3 (BrAcT3). A series of experiments revealed that bromoacetic acid, probably present as a side reaction product in the sample solution, was responsible. This compound repressed the ionization of the carboxyl group of BrAcT3 forcing it into the less polar stationary phase until the bromoacetic acid had eluted completely from the apparatus. At this point, the sudden increase of pH and consequent ionization of the BrAcT3 allowed the ammonium salt of the latter to enter the more polar moving phase where it eluted rapidly from the column as a sharp peak. The same phenomenon was observed in the CCC fractionation of a series of indole auxins where addition of trifluoroacetic acid to the sample caused peak sharpening by the same process. The phenomenon recalls pH gradient elution and isoelectric focussing except that the substance responsible for the pH range here is added along with the sample in one bolus forming a sharp pH gradient at its trailing edge. As with gradient elution, the technique is of practical interest since it permits collection of the eluting compounds with increased detectability in fewer fractions. The technique can also enhance separation of compounds whose partition coefficients differ with a change in pH. C1 NIDDKD,BETHESDA,MD 20892. RP ITO, Y (reprint author), NHLBI,BIOPHYS CHEM LAB,BLDG 10,ROOM 7N322,BETHESDA,MD 20892, USA. NR 9 TC 12 Z9 12 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD NOV 20 PY 1992 VL 625 IS 2 BP 177 EP 181 DI 10.1016/0021-9673(92)85200-D PG 5 WC Chemistry, Analytical SC Chemistry GA KA517 UT WOS:A1992KA51700012 PM 1474121 ER PT J AU CRIPPA, MP ALFONSO, PJ BUSTIN, M AF CRIPPA, MP ALFONSO, PJ BUSTIN, M TI NUCLEOSOME CORE BINDING REGION OF CHROMOSOMAL PROTEIN HMG-17 ACTS AS AN INDEPENDENT FUNCTIONAL DOMAIN SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIGH MOBILITY GROUP PROTEINS; FUNCTIONAL DOMAIN; CHROMATIN; NUCLEOSOME ID MOBILITY GROUP PROTEIN-14; DNA; CHROMATIN; PARTICLES; COMPLEX; HMG14 RP CRIPPA, MP (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. RI crippa, massimo/J-6514-2016; Bustin, Michael/G-6155-2015 OI crippa, massimo/0000-0003-3214-9670; NR 24 TC 58 Z9 58 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 20 PY 1992 VL 228 IS 2 BP 442 EP 449 DI 10.1016/0022-2836(92)90833-6 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA676 UT WOS:A1992KA67600015 PM 1453455 ER PT J AU SMITH, RH WLADKOWSKI, BD HERLING, JA PFALTZGRAFF, TD TAYLOR, JE THOMPSON, EJ PRUSKI, B KLOSE, JR MICHEJDA, CJ AF SMITH, RH WLADKOWSKI, BD HERLING, JA PFALTZGRAFF, TD TAYLOR, JE THOMPSON, EJ PRUSKI, B KLOSE, JR MICHEJDA, CJ TI NOVEL TRIAZENES AND TRIAZOLINES FROM THE BASE-CATALYZED-HYDROLYSIS OF 1,3-DIALKYL-3-ACYLTRIAZENES SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ALKYLATING-AGENTS; DECOMPOSITION; 1,3-DIALKYLTRIAZENES; ION AB The products and mechanism of hydrolytic decomposition of a series of 1,3-dialkyl-3-acyltriazenes were studied in alkaline buffers. In general the mechanism of decomposition involves deacylation leading to the formation of the parent 1,3-dialkyltriazene. The solvent deuterium isotope effect (k(H2O)/k(D2O)) is less than 1.0, indicating specific base catalysis. A plausible mechanistic explanation is rapid reversible attack by hydroxide ion, followed by rate-limiting heterolysis of the N(l)-acyl bond. The resultant, 1,3-dialkyltriazene is somewhat unstable under the reaction conditions and undergoes subsequent hydrolysis, a reaction previously shown to be specific acid-catalyzed. When the N(l) alkyl group is 2-chloroethyl, unusual products are obtained. For the 3-acetyl and 3-carbethoxy derivatives, the initial deacylation product, 1-(2-chloroethyl)-3-methyltriazene, efficiently cyclizes to form 1-methyltriazoline. The 3-(methylcarbamoyl) derivative does not deacylate, but instead undergoes dehydrohalogenation to 1-vinyl-3-methyl-3-(methylcarbamoyl)triazene. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYN CORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. RP SMITH, RH (reprint author), WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157, USA. NR 21 TC 9 Z9 9 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 20 PY 1992 VL 57 IS 24 BP 6448 EP 6454 DI 10.1021/jo00050a016 PG 7 WC Chemistry, Organic SC Chemistry GA JZ579 UT WOS:A1992JZ57900016 ER PT J AU POZSGAY, V GLAUDEMANS, CPJ ROBBINS, JB SCHNEERSON, R AF POZSGAY, V GLAUDEMANS, CPJ ROBBINS, JB SCHNEERSON, R TI SYNTHESIS OF A TETRASACCHARIDE BUILDING BLOCK OF THE O-SPECIFIC POLYSACCHARIDE OF SHIGELLA-DYSENTERIAE TYPE-1 SO TETRAHEDRON LA English DT Article ID ARTIFICIAL CARBOHYDRATE ANTIGENS; B STREPTOCOCCAL POLYSACCHARIDES; VARIANT-Y POLYSACCHARIDE; BINDING-SITE PROBES; BRUCELLA-A-ANTIGEN; REPEATING-UNIT; CHEMICAL SYNTHESIS; ANTITHROMBIN-III; STEREOSELECTIVE SYNTHESIS; CAPSULAR POLYSACCHARIDE AB A glycosyl trichloroacetimidate derivative (1) of the tetrasaccharide alpha-D-Galp-(1 --> 3)-alpha-D-GlcpNAc-(1 --> 3)-alpha-L-Rhap-(1 --> 3)-alpha-L-Rhap was synthesized in a highly stereoselective, stepwise manner, using methyl 1-thioglycosides of L-rhamnose, 2-azido-2-deoxy-D-glucose and D-galactose, as major intermediates. The protecting group scenario in compound 1 permits regioselective deblocking at its "non-reducing end" unit. Therefore 1 is a suitable intermediate for the preparation of extended fragments of the title polysaccharide. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP POZSGAY, V (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BLDG 8,RM B1A-25,BETHESDA,MD 20892, USA. NR 86 TC 29 Z9 30 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD NOV 20 PY 1992 VL 48 IS 47 BP 10249 EP 10264 DI 10.1016/S0040-4020(01)88331-9 PG 16 WC Chemistry, Organic SC Chemistry GA KA257 UT WOS:A1992KA25700005 ER PT J AU NARA, P TSAI, WP KUNG, HF MINASSIAN, A GARRITY, R GOUDSMIT, J RIMMELZWAAN, G AF NARA, P TSAI, WP KUNG, HF MINASSIAN, A GARRITY, R GOUDSMIT, J RIMMELZWAAN, G TI UNIVERSAL CELLULAR TROPISM SO NATURE LA English DT Letter ID HIV-1; REGIONS; GP120 C1 UNIV AMSTERDAM,ACAD MED CTR,DEPT VIROL,1105 AZ AMSTERDAM,NETHERLANDS. RP NARA, P (reprint author), NCI,FREDERICK,MD 21702, USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 19 PY 1992 VL 360 IS 6401 BP 215 EP 216 DI 10.1038/360215b0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY960 UT WOS:A1992JY96000033 PM 1359427 ER PT J AU VUISTER, GW DELAGLIO, F BAX, A AF VUISTER, GW DELAGLIO, F BAX, A TI AN EMPIRICAL CORRELATION BETWEEN 1J(C-ALPHA-H-ALPHA) AND PROTEIN BACKBONE CONFORMATION SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID PANCREATIC TRYPSIN-INHIBITOR; SPIN COUPLING-CONSTANTS; STAPHYLOCOCCAL NUCLEASE; NMR-SPECTROSCOPY; CALMODULIN; RESONANCE; C-13; H-1; ASSIGNMENTS; DEPENDENCE C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NR 18 TC 69 Z9 69 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 18 PY 1992 VL 114 IS 24 BP 9674 EP 9675 DI 10.1021/ja00050a066 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA JZ236 UT WOS:A1992JZ23600066 ER PT J AU HAWKINS, MJ FRIEDMAN, MA AF HAWKINS, MJ FRIEDMAN, MA TI NATIONAL-CANCER-INSTITUTES EVALUATION OF UNCONVENTIONAL CANCER TREATMENTS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,EXECUT PLAZA N,RM 742,BETHESDA,MD 20892. NR 10 TC 14 Z9 15 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 18 PY 1992 VL 84 IS 22 BP 1699 EP 1702 DI 10.1093/jnci/84.22.1699 PG 4 WC Oncology SC Oncology GA JY177 UT WOS:A1992JY17700009 PM 1433356 ER PT J AU BINASCHI, M GIACCONE, G GAZDAR, AF DEISABELLA, P RICOTTI, GCBA CAPRANICO, G ZUNINO, F AF BINASCHI, M GIACCONE, G GAZDAR, AF DEISABELLA, P RICOTTI, GCBA CAPRANICO, G ZUNINO, F TI CHARACTERIZATION OF A TOPOISOMERASE-II GENE REARRANGEMENT IN A HUMAN SMALL-CELL LUNG-CANCER CELL-LINE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-LEUKEMIA-CELLS; DNA CLEAVAGE; MULTIDRUG RESISTANCE; DRUG-RESISTANCE; ETOPOSIDE; INHIBITORS; EXPRESSION; ADRIAMYCIN; AMSACRINE; IDENTIFICATION AB Background: Small-cell lung cancer (SCLC) is a highly chemosensitive tumor, but the recurrent disease that is common after initial response is often unresponsive to further chemotherapy. Although the mechanisms of drug resistance in SCLC have not been established, studies suggest that alterations of the nuclear enzyme DNA topoisomerase II may reduce the sensitivity of the cell to drug action. This enzyme is recognized as a primary target for cytotoxic activity of important antitumor agents. Purpose: In this study, we attempted to determine if altered forms of DNA topoisomerase II are responsible for reduced drug sensitivity. Methods: We characterized a rearrangement of the topoisomerase II p170 gene (also known as TOP2) in a relatively chemoresistant SCLC cell line, NCI-H69, and compared topoisomerase II expression and activity in this line with those in the chemosensitive NCI-H187 cell line. Fragments of complementary DNA from the topoisomerase II gene were generated by polymerase chain reaction. Immunodetection was accomplished by using the monoclonal antibody 7E6 against the human topoisomerase II p170 isoform. Using DNA probes corresponding to different complementary DNA regions, we showed that the rearrangement was localized at the 3'-terminus of one allele of the topoisomerase II gene. Results: In addition to the normal 6.2-kilobase (kb) topoisomerase II messenger RNA (mRNA), the NCI-H69 line expressed a 7.4-kb topoisomerase II transcript, presumably encoded by the rearranged allele. Moreover, this transcript, although longer than the normal mRNA, lacked a substantial portion of the 3'-terminal p170 gene coding sequence. Topoisomerase II activity in nuclear extracts, as determined by the P4 phage DNA-unknotting assay, was more easily detected and measured at lower NaCl concentrations in NCI-H69 than in NCI-H187 cells. Conclusion: These results are consistent with the hypothesis that the chemoresistant NCI-H69 cell line may express. in addition to the normal enzyme, an altered topoisomerase II enzyme possibly encoded by the 7.4-kb mRNA, which in turn may be transcribed from the rearranged gene allele. Implication: These observations emphasize the role of topoisomerase II in determining drug sensitivity and suggest that such gene rearrangements may contribute to resistance of SCLC cells to topoisomerase II inhibitors. C1 IST NAZL STUDIO & CURA TUMORI,DIV EXPTL ONCOL B,I-20133 MILAN,ITALY. CNR,IST GENET BIOCHIM & EVOLUZ,I-27100 PAVIA,ITALY. NCI,DIV CANC TREATMENT,USN,MED ONCOL BRANCH,BETHESDA,MD 20892. RI Capranico, Giovanni/K-1678-2014; Giaccone, Giuseppe/E-8297-2017 OI Capranico, Giovanni/0000-0002-8708-6454; Giaccone, Giuseppe/0000-0002-5023-7562 NR 41 TC 22 Z9 22 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 18 PY 1992 VL 84 IS 22 BP 1710 EP 1716 DI 10.1093/jnci/84.22.1710 PG 7 WC Oncology SC Oncology GA JY177 UT WOS:A1992JY17700011 PM 1331483 ER PT J AU KAUR, G STETLERSTEVENSON, M SEBERS, S WORLAND, P SEDLACEK, H MYERS, C CZECH, J NAIK, R SAUSVILLE, E AF KAUR, G STETLERSTEVENSON, M SEBERS, S WORLAND, P SEDLACEK, H MYERS, C CZECH, J NAIK, R SAUSVILLE, E TI GROWTH-INHIBITION WITH REVERSIBLE CELL-CYCLE ARREST OF CARCINOMA-CELLS BY FLAVONE-L86-8275 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CANCER-CELLS; PROTEIN; QUERCETIN; KINASE; FLAVONOIDS AB Background: Previous studies have shown that polyhydroxylated flavonoids such as quercetin and genistein can inhibit tumor cell growth in vitro, and preliminary in vivo studies of the flavone L86-8275 have shown growth inhibition of LX529 and A549 lung carcinomas. L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8[4-(3-hydroxy-1-methyl)-piperidinyl]-4H-1-benzopyran-4-one] is a flavone of novel structure. Purpose: The purpose of this study was to determine in vitro whether L86-8275 is a more potent inhibitor of growth in breast carcinoma and lung carcinoma cells than quercetin or genistein. Methods: We studied the effects of L86-8275 on cell growth in seven breast carcinoma cell lines and five lung carcinoma cell lines. MDA468 breast carcinoma was then selected for further study. Cell proliferation was measured by a colorimetric dye reduction assay; synthesis of DNA, RNA, and protein by incorporation of the radioactive metabolic precursors thymidine, uridine, or leucine, respectively; adenosine triphosphate (ATP) content by a luciferase-mediated bioluminescence reaction; and cell cycle progression by the use of cell-synchronizing drugs (aphidicolin and nocodazole) and flow cytometry. Results: L86-8275 was not cytotoxic to stationary-phase cells but reversibly inhibited the growth of cells in exponential growth phase. At concentrations of 25-160 nM. L86-8275 inhibited growth of human breast and lung carcinoma cell lines by 50%. MDA468 breast carcinoma cells were 60-fold and 400-fold more sensitive to L86-8275 than to quercetin and genistein, respectively. By 24 hours after addition of L86-8275, DNA synthesis in MDA468 cells was inhibited by greater than 95%, protein synthesis by 80%, and RNA synthesis by 40%-60%, under conditions that preserved cellular ATP levels at approximately 80%-90% of control values. When MDA468 cells released from aphidicolin-induced cell cycle arrest were exposed to 200 nM L86-8275, they completed the S phase but arrested in G2. When cells released from nocodazole-induced cell cycle arrest were exposed to 200 nM L86-8275, they completed mitosis but arrested in G1. Conclusions: L86-8275 is a potent, yet reversible, growth-inhibitory flavone that can selectively block cell cycle progression in vitro at more than one point in the cell cycle. Implications: These findings suggest that L86-8275 is a candidate for further preclinical development, as well as a model for the synthesis of other flavonoids that might potently delay cell cycle progression to achieve inhibition of tumor growth. Future studies need to address optimal schedules for antiproliferative activity in vivo and inhibition of clonogenic activity. C1 NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BLDG 37,RM 5D02,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAGN & CTR,PATHOL LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. BEHRINGWERKE AG,W-3550 MARBURG,GERMANY. NR 20 TC 280 Z9 282 U1 1 U2 8 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 18 PY 1992 VL 84 IS 22 BP 1736 EP 1740 DI 10.1093/jnci/84.22.1736 PG 5 WC Oncology SC Oncology GA JY177 UT WOS:A1992JY17700015 PM 1279187 ER PT J AU LAKSHMAN, MK YEH, HJC YAGI, H JERINA, DM AF LAKSHMAN, MK YEH, HJC YAGI, H JERINA, DM TI SYNTHESIS OF DEOXYADENOSINE ADDUCTS FROM THE HIGHLY CARCINOGENIC FJORD REGION DIOL EPOXIDE OF BENZO[C]PHENANTHRENE SO TETRAHEDRON LETTERS LA English DT Article DE POLYCYCLIC HYDROCARBONS; BENZO[C]PHENANTHRENE 3,4-DIOL 1,2-EPOXIDE; DEOXYADENOSINE ADDUCTS ID LIVER MICROSOMES; DNA; CYTOCHROME-P-450; METABOLISM; SYSTEM; RAT AB Unlike bay-region diol epoxides, the fjord-region benzo[c]phenanthrene 3,4-diol 1,2-epoxide-2 (4-hydroxyl and epoxide oxygen trans) undergoes non-regioselective ring opening by both ammonia and azide anion. Adducts corresponding to a benzylic and non-benzylic S(N)2 ring opening by N6 of deoxyadenosine have been characterized. C1 NIDDK,BIOORGAN & ANALYT CHEM LAB,BETHESDA,MD 20892. NR 16 TC 13 Z9 13 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD NOV 17 PY 1992 VL 33 IS 47 BP 7121 EP 7124 DI 10.1016/S0040-4039(00)60852-3 PG 4 WC Chemistry, Organic SC Chemistry GA JY861 UT WOS:A1992JY86100013 ER PT J AU QUELLE, FW EGERTON, M SAMELSON, LE WOJCHOWSKI, DM AF QUELLE, FW EGERTON, M SAMELSON, LE WOJCHOWSKI, DM TI CYTOKINE-INDUCED PHOSPHORYLATION OF PP100 IN FDC-ER CELLS IS AT TYROSINE RESIDUES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID COLONY-STIMULATING FACTOR; RECEPTOR SUPERFAMILY; SIGNAL TRANSDUCTION; ERYTHROPOIETIN; INTERLEUKIN-3; PROTEIN; EXPRESSION; SERINE; GROWTH C1 PENN STATE UNIV,DEPT MOLEC & CELL BIOL,408 S FREAR LAB,UNIV PK,PA 16802. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL44491]; NIDDK NIH HHS [R29-DK40242] NR 26 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 NOV 16 PY 1992 VL 188 IS 3 BP 1040 EP 1046 DI 10.1016/0006-291X(92)91336-O PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JY446 UT WOS:A1992JY44600012 PM 1280128 ER PT J AU SHEIKH, MS SHAO, ZM CHEN, JC CLEMMONS, DR ROBERTS, CT LEROITH, D FONTANA, JA AF SHEIKH, MS SHAO, ZM CHEN, JC CLEMMONS, DR ROBERTS, CT LEROITH, D FONTANA, JA TI INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-5 GENE-EXPRESSION IS DIFFERENTIALLY REGULATED AT A POSTTRANSCRIPTIONAL LEVEL IN RETINOIC ACID-SENSITIVE AND RESISTANT MCF-7 HUMAN BREAST-CARCINOMA CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MESSENGER-RNA STABILITY; 3' UNTRANSLATED REGION; IGF-II RECEPTORS; MOLECULAR-CLONING; CANCER-CELLS; TRANSFERRIN RECEPTOR; C-FOS; IDENTIFICATION; DEGRADATION; INHIBITION C1 UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. VET ADM MED CTR,BALTIMORE,MD 21201. NIDDK,DIABET BRANCH,BETHESDA,MD 20892. UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC 27514. RP SHEIKH, MS (reprint author), UNIV MARYLAND,DEPT MED,BALTIMORE,MD 21201, USA. OI Fontana, Joseph/0000-0003-3829-3358; Roberts, Charles/0000-0003-1756-5772 NR 29 TC 11 Z9 11 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 NOV 16 PY 1992 VL 188 IS 3 BP 1122 EP 1130 DI 10.1016/0006-291X(92)91348-T PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JY446 UT WOS:A1992JY44600024 PM 1280130 ER PT J AU MAUTNER, SL LIN, F ROBERTS, WC AF MAUTNER, SL LIN, F ROBERTS, WC TI COMPOSITION OF ATHEROSCLEROTIC PLAQUES IN THE EPICARDIAL CORONARY-ARTERIES IN JUVENILE (TYPE-I) DIABETES-MELLITUS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MORPHOMETRIC ANALYSIS; AGE AB The composition of atherosclerotic plaques in 331 five-mm segments of the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries of 8 patients with juvenile (mean age at onset, 9 years; mean age at death, 29 years) diabetes mellitus was determined by computerized planimetric analysis. Analysis of all coronary segments disclosed that the plaques consisted primarily of dense (53%) and cellular (38%) fibrous tissue. Pultaceous debris (7%), foam cells (1.2%) and calcific deposits (0.7%) occupied a small percentage of the plaques. Thus, 91% of the coronary plaques in these young diabetic patients consisted of fibrous tissue and nearly all of the remaining 9% consisted of lipid deposits. Analysis of composition according to degrees of cross-sectional luminal narrowing revealed marked increases in dense fibrous tissue (from 31 to 74%), pultaceous debris (from 3 to 12%), and calcific deposits (from 0% to 3%) as the cross-sectional area narrowing increased from less-than-or-equal-to 25% to >75%. Compared with older patients with juvenile diabetes had more dense fibrous tissue and puitaceous debris and less calcific deposits. RP MAUTNER, SL (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 22 Z9 22 U1 1 U2 1 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 NOV 15 PY 1992 VL 70 IS 15 BP 1264 EP 1268 DI 10.1016/0002-9149(92)90759-R PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JY231 UT WOS:A1992JY23100006 PM 1442576 ER PT J AU KURIBAYASHI, T ROBERTS, WC AF KURIBAYASHI, T ROBERTS, WC TI MYOCARDIAL DISARRAY AT JUNCTION OF VENTRICULAR SEPTUM AND LEFT AND RIGHT VENTRICULAR FREE WALLS IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MUSCLE; HEART; STENOSIS; FEATURES; DISEASE AB The abnormality of the myocardium in hearts with hypertrophic cardiomyopathy (HC) was assessed regarding whether the muscle bundle in the midwall layer maintains its normal circular and continuous orientation surrounding the left ventricular (LV) cavity. Forty-seven autopsied hearts with HC were examined. The LV wall midway between the base and apex was divided into 6 segments in the transverse plane. Histologically, the circular orientation was destroyed largely or completely due to marked fascicle disarray in 77% of the anterior and posterior junctional segments. In 33% of the middle portion of the ventricular septum and in 34% of the anterior and posterior portions of the LV free wall, the midwall layer showed disarray of muscle fibers or small fascicles. In contrast, the lateral LV free wall was devoid of disarranged fibers in its midwall layer. Myocardial fibrosis usually was predominant in the portion where disarray was marked. There were deep tissue clefts often in the area of junction. In 11 hearts (7 from patients aged >65 years), the circular unit was intact in almost every segment, as it was in 9 of 10 control hearts. The destruction of the circular unit in the area of septal-free wall junctions in most patients with HC is a previously undescribed morphologic feature of HC. This discontinuity may result from retention of an abnormal fetal myocardial architecture in which the septal latitudinal muscle was continuous with the right ventricular free wall. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 31 TC 75 Z9 76 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 NOV 15 PY 1992 VL 70 IS 15 BP 1333 EP 1340 DI 10.1016/0002-9149(92)90771-P PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JY231 UT WOS:A1992JY23100018 PM 1442587 ER PT J AU GALDERISI, M BENJAMIN, EJ EVANS, JC DAGOSTINO, RB FULLER, DL LEHMAN, B WOLF, PA LEVY, D AF GALDERISI, M BENJAMIN, EJ EVANS, JC DAGOSTINO, RB FULLER, DL LEHMAN, B WOLF, PA LEVY, D TI INTRAOBSERVER AND INTEROBSERVER REPRODUCIBILITY OF DOPPLER-ASSESSED INDEXES OF LEFT-VENTRICULAR DIASTOLIC FUNCTION IN A POPULATION-BASED STUDY (THE FRAMINGHAM HEART-STUDY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FLOW VELOCITY PATTERNS; ECHOCARDIOGRAPHY AB The reproducibility of a variety of Doppler indexes of diastolic function in an epidemiologic setting and in atrial fibrillation have not been reported. This study examined the reproducibility of left ventricular inflow in subjects in sinus rhythm (n = 80) and atrial fibrillation (n = 12), randomly selected from the original cohort of the Framing-ham Heart Study. The following Doppler indexes were assessed for all subjects: peak and integral of early (E) diastolic inflow velocity, acceleration slope and time, deceleration slope and time, and pressure half-time. For subjects in sinus rhythm, the following parameters also were measured: the peak and integral of late (A) diastolic inflow velocity, ratios of peak velocities and integrals E/A, and atrial filling fraction. Intraobserver and interobserver variability were evaluated by statistical methods including Student's t test of the systematic differences (bias), percent bias, correlation coefficients, measurement precision, and percent precision. In subjects in sinus rhythm, although the interobserver blas was statistically significant for most of the parameters, it was <10% for all but 1 parameter (acceleration time). For the peak and integral measures, the intra- and interobserver correlations were greater-than-or-equal-to 0.89, with intra- and interobserver percent precision measures within 2.2 to 13.0% of the corresponding mean values. The acceleration, deceleration and pressure half-time measures had somewhat lower correlations (interobserver correlations ranging from 0.59 to 0.96), with percent precision measures further from the corresponding means (interobserver percent precision ranging from 10.1 to 19.5%). The analyses of subjects with atrial fibrillation showed similar trends, despite the biologic (cycle-to-cycle) variability intrinsic to this arrhythmia. In conclusion, in an epidemiologic setting, the majority of Doppler indexes of diastolic function demonstrate excellent measurement reproducibility, especially the peak and time velocity integral measurements. Measurement variability may limit the reproducibility of early diastolic acceleration and deceleration parameters. C1 BOSTON CITY HOSP, DEPT CARDIOL, FRAMINGHAM HEART STUDY, 5 THURBER ST, FRAMINGHAM, MA 01701 USA. BOSTON UNIV, DEPT MATH, BOSTON, MA 02215 USA. BOSTON UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02118 USA. BOSTON UNIV, SCH MED, DEPT PREVENT MED, BOSTON, MA 02118 USA. BETH ISRAEL HOSP, DIV CARDIOL & CLIN EPIDEMIOL, BOSTON, MA 02215 USA. NHLBI, BETHESDA, MD 20892 USA. NAPLES UNIV, SCH MED 2, I-80138 NAPLES, ITALY. OI Galderisi, Maurizio/0000-0003-0311-9069 FU NHLBI NIH HHS [1-HC-38038]; NINDS NIH HHS [2-RO1-NS-17950-09] NR 20 TC 56 Z9 56 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 1992 VL 70 IS 15 BP 1341 EP 1346 DI 10.1016/0002-9149(92)90772-Q PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JY231 UT WOS:A1992JY23100019 PM 1442588 ER PT J AU DOMANSKI, MJ CUNNION, RE ROBERTS, WC AF DOMANSKI, MJ CUNNION, RE ROBERTS, WC TI ANALYSIS OF FRACTIONAL AREA CHANGE AT VARIOUS LEVELS IN THE NORMAL LEFT-VENTRICLE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. RP DOMANSKI, MJ (reprint author), NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 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 NOV 15 PY 1992 VL 70 IS 15 BP 1367 EP 1368 DI 10.1016/0002-9149(92)90777-V PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JY231 UT WOS:A1992JY23100024 PM 1442593 ER PT J AU BEREZOWSKI, K MAUTNER, GC ROBERTS, WC AF BEREZOWSKI, K MAUTNER, GC ROBERTS, WC TI SCARRING OF THE LEFT-VENTRICULAR PAPILLARY-MUSCLES IN SICKLE-CELL DISEASE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID ANEMIA; HEART RP BEREZOWSKI, K (reprint author), NHLBI,PATHOL BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 7 Z9 8 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 NOV 15 PY 1992 VL 70 IS 15 BP 1368 EP 1370 DI 10.1016/0002-9149(92)90778-W PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JY231 UT WOS:A1992JY23100025 PM 1442594 ER PT J AU BOYER, TD KEMPNER, ES AF BOYER, TD KEMPNER, ES TI EFFECT OF SUBUNIT INTERACTIONS ON ENZYMATIC-ACTIVITY OF GLUTATHIONE S-TRANSFERASES - A RADIATION INACTIVATION STUDY SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID RAT-LIVER; BINDING; PROTEIN; PRODUCT; TARGET C1 NIAMSD, PHYS BIOL LAB, BETHESDA, MD 20892 USA. RP BOYER, TD (reprint author), EMORY UNIV, SCH MED, DIV DIGEST DIS, ATLANTA, GA 30322 USA. FU NIGMS NIH HHS [GM-31555] NR 31 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 15 PY 1992 VL 207 IS 1 BP 51 EP 57 DI 10.1016/0003-2697(92)90498-V PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JY580 UT WOS:A1992JY58000009 PM 1489099 ER PT J AU STERNBERG, EM CHROUSOS, GP WILDER, RL GOLD, PW AF STERNBERG, EM CHROUSOS, GP WILDER, RL GOLD, PW TI THE STRESS RESPONSE AND THE REGULATION OF INFLAMMATORY DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE STRESS; INFLAMMATION; ANTIDEPRESSIVE AGENTS; CYTOKINES; CORTICOTROPIN-RELEASING HORMONE ID CORTICOTROPIN-RELEASING HORMONE; EOSINOPHILIA-MYALGIA-SYNDROME; PITUITARY-ADRENAL AXIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; IMMUNODEFICIENCY-SYNDROME; CLINICAL IMPLICATIONS; CUSHINGS-DISEASE; NERVOUS-SYSTEM; TRYPTOPHAN USE AB The molecular and biochemical bases for interactions between the immune and central nervous systems are described. Immune cytokines not only activate immune function but also recruit central stress-responsive neurotransmitter systems in the modulation of the immune response and in the activation of behaviors that may be adaptive during injury or inflammation. Peripherally generated cytokines, such as interleukin-1, signal hypothalamic corticotropin-releasing hormone (CRH) neurons to activate pituitary-adrenal counter-regulation of inflammation through the potent anti-inflammatory effects of glucocorticoids. Corticotropin-releasing hormone not only activates the pituitary-adrenal axis but also sets in motion a coordinated series of behavioral and physiologic responses, suggesting that the central nervous system may coordinate both behavioral and immunologic adaptation during stressful situations. The pathophysiologic perturbation of this feedback loop, through various mechanisms, results in the development of inflammatory syndromes, such as rheumatoid arthritis, and behavioral syndromes, such as depression. Thus, diseases characterized by both inflammatory and emotional disturbances may derive from common alterations in specific central nervous system pathways (for example, the CRH system). In addition, disruptions of this communication by genetic, infectious, toxic, or pharmacologic means can influence the susceptibility to disorders associated with both behavioral and inflammatory components and potentially alter their natural history. These concepts suggest that neuropharmacologic agents that stimulate hypothalamic CRH might potentially be adjunctive therapy for illnesses traditionally viewed as inflammatory or autoimmune. C1 NIAMSD, BETHESDA, MD 20892 USA. RP NIMH, BLDG 10, ROOM 3S-231, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 87 TC 325 Z9 328 U1 1 U2 18 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 15 PY 1992 VL 117 IS 10 BP 854 EP 866 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA JX838 UT WOS:A1992JX83800010 PM 1416562 ER PT J AU SHARARA, FI CHROUSOS, GP PATRONAS, NJ AF SHARARA, FI CHROUSOS, GP PATRONAS, NJ TI WATCHFUL WAITING AND CRANIOPHARYNGIOMA SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP SHARARA, FI (reprint author), NIH,BETHESDA,MD 20892, USA. NR 5 TC 2 Z9 2 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 NOV 15 PY 1992 VL 117 IS 10 BP 876 EP 877 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JX838 UT WOS:A1992JX83800023 PM 1416569 ER PT J AU SHI, XL DALAL, NS KASPRZAK, KS AF SHI, XL DALAL, NS KASPRZAK, KS TI GENERATION OF FREE-RADICALS FROM LIPID HYDROPEROXIDES BY NI2+ IN THE PRESENCE OF OLIGOPEPTIDES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID SPIN TRAP 5,5-DIMETHYL-1-PYRROLINE-1-OXIDE; TERT-BUTYL HYDROPEROXIDE; DNA DAMAGE; PEROXIDATION PRODUCTS; NICKEL CARCINOGENESIS; CUMENE HYDROPEROXIDE; BIOLOGICAL-SYSTEMS; HYDROGEN-PEROXIDE; HYDROXYL RADICALS; HEMATIN SYSTEM C1 W VIRGINIA UNIV,DEPT CHEM,MORGANTOWN,WV 26506. RP SHI, XL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. RI Shi, Xianglin/B-8588-2012 NR 63 TC 45 Z9 46 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 1992 VL 299 IS 1 BP 154 EP 162 DI 10.1016/0003-9861(92)90257-W PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JV613 UT WOS:A1992JV61300022 PM 1332613 ER PT J AU PATTEN, CJ ISHIZAKI, H AOYAMA, T LEE, MJ NING, SM HUANG, W GONZALEZ, FJ YANG, CS AF PATTEN, CJ ISHIZAKI, H AOYAMA, T LEE, MJ NING, SM HUANG, W GONZALEZ, FJ YANG, CS TI CATALYTIC PROPERTIES OF THE HUMAN CYTOCHROME-P450 2E1 PRODUCED BY CDNA EXPRESSION IN MAMMALIAN-CELLS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID ETHANOL-INDUCIBLE CYTOCHROME-P-450; RAT-LIVER MICROSOMES; N-NITROSODIMETHYLAMINE; PARA-NITROPHENOL; METABOLISM; PURIFICATION; ACETONE; BINDING; B5; RECONSTITUTION C1 RUTGERS STATE UNIV,COLL PHARM,CANC RES LAB,PISCATAWAY,NJ 08855. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NIEHS NIH HHS [ES 03938, ES 05022] NR 45 TC 86 Z9 86 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 15 PY 1992 VL 299 IS 1 BP 163 EP 171 DI 10.1016/0003-9861(92)90258-X PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JV613 UT WOS:A1992JV61300023 PM 1444447 ER PT J AU BREIER, A DAVIS, O BUCHANAN, R LISTWAK, SJ HOLMES, C PICKAR, D GOLDSTEIN, DS AF BREIER, A DAVIS, O BUCHANAN, R LISTWAK, SJ HOLMES, C PICKAR, D GOLDSTEIN, DS TI EFFECTS OF ALPRAZOLAM ON PITUITARY-ADRENAL AND CATECHOLAMINERGIC RESPONSES TO METABOLIC STRESS IN HUMANS SO BIOLOGICAL PSYCHIATRY LA English DT Article ID SYMPATHETIC NERVOUS-SYSTEM; PLASMA-CATECHOLAMINE; BENZODIAZEPINE RECEPTOR; CORTICOSTERONE LEVELS; BRAIN CATECHOLAMINES; RATS; NOREPINEPHRINE; DIAZEPAM; ANXIETY; CHLORDIAZEPOXIDE AB Concrurrent effects of benzodiazepines on stress-induced activation of the three classical "stress" systems: pituitary-adrenal, adrenomedullary, and sympathoneural systems have not been extensively investigated in humans. In the present study, the effects of alprazolam (1.5 mg) on plasma levels of adrenocorticotropin hormone (ACTH), epinephrine, norepinephrine, dihydroxyphenylglycol (DHPG, the intraneuronal metabolite of norepinephrine), and mood states were examined in 10 healthy volunteers undergoing glucoprivic stress. Glucoprivic stress was induced by intravenous administration of the glucose analog, 2-deoxyglucose (2DG), at a dose (50 mg/kg) that impairs cellular glucose metabolism and produces a state comparable to hypoglycemia. Alprazolam and 2DG were administered in a double-blind, placebo-controlled manner. 2DG produced robust elevations in plasma ACTH and epinephrine levels, modest elevations in plasma norepinephrine levels, and decreases in plasma DHPG levels. Alprazolam significantly attenuated the 2DG-induced increases in plasma ACTH and epinephrine, but did not significantly effect plasma norepinephrine and DHPG. These data suggest that benzodiazepines attenuate metabolic stress-induced activation of the pituitary-adrenal and adrenomedullary systems but do not effect 2DG-related effects on peripheral sympathoneural function. The possible mechanisms involved are discussed. C1 NINCDS,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP BREIER, A (reprint author), UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,MARYLAND PSYCHIAT RES CTR,POB 21247,CATONSVILLE,MD 21228, USA. FU NIMH NIH HHS [MH40279] NR 41 TC 40 Z9 40 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1992 VL 32 IS 10 BP 880 EP 890 DI 10.1016/0006-3223(92)90177-2 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KC871 UT WOS:A1992KC87100004 PM 1334713 ER PT J AU MCCANN, UD RICAURTE, GA AF MCCANN, UD RICAURTE, GA TI MDMA (ECSTASY) AND PANIC DISORDER - INDUCTION BY A SINGLE DOSE SO BIOLOGICAL PSYCHIATRY LA English DT Article ID PSYCHOSIS C1 WALTER REED ARMY INST RES,DEPT BEHAV BIOL,WASHINGTON,DC 20307. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. RP MCCANN, UD (reprint author), NIMH,ANXIETY & AFFECT DISORDERS SECT,BLDG 10,ROOM 3S-239,BETHESDA,MD 20892, USA. FU NIDA NIH HHS [DA 05938] NR 14 TC 53 Z9 53 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1992 VL 32 IS 10 BP 950 EP 953 DI 10.1016/0006-3223(92)90185-3 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KC871 UT WOS:A1992KC87100012 PM 1361366 ER PT J AU KMIECIK, TE KELLER, JR ROSEN, E VANDEWOUDE, GF AF KMIECIK, TE KELLER, JR ROSEN, E VANDEWOUDE, GF TI HEPATOCYTE GROWTH-FACTOR IS A SYNERGISTIC FACTOR FOR THE GROWTH OF HEMATOPOIETIC PROGENITOR CELLS SO BLOOD LA English DT Note ID MET PROTO-ONCOGENE; SCATTER FACTOR; C-MET; MOLECULAR-CLONING; EPITHELIAL-CELLS; PROTOONCOGENE; PROLIFERATION; INTERLEUKIN-6; RECEPTOR; MITOGEN C1 NCI,FREDERICK CANC RES & DEV CTR,ABI BASIC RES PROGRAM,POB B,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP INC,PROGRAM RESOURCES INC,FREDERICK,MD 21701. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. FU NCI NIH HHS [N01-CO-74102]; PHS HHS [N01-C0-74101] NR 32 TC 111 Z9 111 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1992 VL 80 IS 10 BP 2454 EP 2457 PG 4 WC Hematology SC Hematology GA JY677 UT WOS:A1992JY67700002 PM 1421367 ER PT J AU HESTDAL, K JACOBSEN, SEW RUSCETTI, FW DUBOIS, CM LONGO, DL CHIZZONITE, R OPPENHEIM, JJ KELLER, JR AF HESTDAL, K JACOBSEN, SEW RUSCETTI, FW DUBOIS, CM LONGO, DL CHIZZONITE, R OPPENHEIM, JJ KELLER, JR TI INVIVO EFFECT OF INTERLEUKIN-1-ALPHA ON HEMATOPOIESIS - ROLE OF COLONY-STIMULATING FACTOR RECEPTOR MODULATION SO BLOOD LA English DT Article ID BONE-MARROW CELLS; GRANULOCYTE-MACROPHAGE; GROWTH-FACTORS; STEM-CELLS; MICE; HEMOPOIETIN-1; PURIFICATION; IL-1; FIBROBLASTS; MECHANISM C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP INC,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP INC,PROGRAM RESOURCES INC,FREDERICK,MD 21701. HOFFMANN LA ROCHE INC,DEPT IMMUNOPHARMACOL & MOLEC GENET,NUTLEY,NJ 07110. FU NCI NIH HHS [N01-CO-74102] NR 40 TC 32 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1992 VL 80 IS 10 BP 2486 EP 2494 PG 9 WC Hematology SC Hematology GA JY677 UT WOS:A1992JY67700007 PM 1384785 ER PT J AU MUSS, HB HUNTER, CP WESLEY, M CORREA, P CHEN, VW GREENBERG, RS ELEY, JW AUSTIN, DF KURMAN, R EDWARDS, BK AF MUSS, HB HUNTER, CP WESLEY, M CORREA, P CHEN, VW GREENBERG, RS ELEY, JW AUSTIN, DF KURMAN, R EDWARDS, BK TI TREATMENT PLANS FOR BLACK-AND-WHITE WOMEN WITH STAGE-II NODE-POSITIVE BREAST-CANCER - THE NATIONAL CANCER INSTITUTE BLACK-WHITE CANCER SURVIVAL STUDY EXPERIENCE SO CANCER LA English DT Article DE BREAST CANCER; RACE; ADJUVANT THERAPY; LUMPECTOMY; NODE POSITIVE; STAGE-II; SURGERY AB Background. The National Cancer Institute Black/White Cancer Survival Study began patient accrual in 1985 and was designed to investigate factors that might contribute to the observed racial differences in survival for cancer of the breast, uterine corpus, colon, and bladder. Methods. To determine whether there were racial differences in treatment in a clinically homogeneous set of patients, 305 (25%) of the 1222 women in this study with Stage II node-positive (N+) breast cancer were evaluated. Results. Patient characteristics for blacks and whites were similar for age, metropolitan area of residence, tumor size, extent of nodal involvement, and steroid receptors. Differences in histologic findings, tumor grade, and nuclear atypia were observed. Blacks had a higher frequency of comorbid conditions, especially hypertension (P < 0.00001). Fewer blacks underwent breast-conserving surgery (P = 0.004). In a multivariate analysis, race was no longer a significant factor in the selection of primary treatment, but education and metropolitan area of residence remained significant. Blacks and whites received similar postoperative systemic therapy, with combination chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and tamoxifen, the most common cytotoxic and endocrine therapies used. Conclusions. The National Cancer Institute consensus statement concerning adjuvant therapy for breast cancer was published in the middle of the 2-year period that study cases were accrued, and treatment plans in this study generally agreed with consensus guidelines. Should survival differences in black and white patients with Stage II N+ disease in this study be found, they are unlikely to be attributable to differences in initial or postoperative treatment. C1 CALIF DEPT HLTH SERV, EMERYVILLE, CA USA. NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. EMORY UNIV, SCH PUBL HLTH, DIV EPIDEMIOL, ATLANTA, GA 30322 USA. JOHNS HOPKINS UNIV HOSP, DEPT PATHOL, BALTIMORE, MD 21205 USA. RP MUSS, HB (reprint author), WAKE FOREST UNIV, CTR COMPREHENS CANC, WINSTON SALEM, NC 27157 USA. NR 16 TC 74 Z9 74 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 1992 VL 70 IS 10 BP 2460 EP 2467 DI 10.1002/1097-0142(19921115)70:10<2460::AID-CNCR2820701012>3.0.CO;2-A PG 8 WC Oncology SC Oncology GA JX894 UT WOS:A1992JX89400011 PM 1423176 ER PT J AU LANCILLOTTI, F DARWICHE, N CELLI, G DE LUCA, LM AF LANCILLOTTI, F DARWICHE, N CELLI, G DE LUCA, LM TI RETINOID STATUS AND THE CONTROL OF KERATIN EXPRESSION AND ADHESION DURING THE HISTOGENESIS OF SQUAMOUS METAPLASIA OF TRACHEAL EPITHELIUM SO CANCER RESEARCH LA English DT Article ID VITAMIN-A-DEFICIENCY; INTERMEDIATE-FILAMENT PROTEINS; LAMININ RECEPTOR; GENE-EXPRESSION; TERMINAL DIFFERENTIATION; CYTOKERATIN SUBFAMILY; MONOCLONAL-ANTIBODY; EPIDERMAL KERATIN; COMPLETE SEQUENCE; GOLDEN-HAMSTERS AB We induced vitamin A depletion to define early and late changes during the histogenesis of squamous metaplasia of hamster tracheal epithelium. An early change is the "minimal morphological change" (MMC), in which the mucociliary epithelium is separated from the basement membrane by a continuous layer of basal cells. Immunohistochemistry showed an exclusive localization of the keratins K5 and K14 in basal cells of normal and MMC epithelia. At the MMC stage no staining was observed above the basal layer with antibodies to K5, but upon progression of the lesion to a squamous focus all cells from basal to terminally differentiated were positive for K5 and K14. In contrast, when we used antibodies to the keratins K6 or K13 all cells were negative in the normal epithelium and in the MMC epithelium. Successive layers of suprabasal squamous cells found in squamous metaplasia failed to express normal epidermal differentiation marker keratins K1 and K10 but expressed the proliferation marker keratin K6 and the internal stratified epithelium keratin K13, not normally found in the epidermis or in the trachea. Hamster tracheal epithelial cells could be maintained in culture in serum-free medium for at least 4 weeks in the presence of retinoic acid (RA). In non-RA-containing medium, cells from vitamin A-deficient hamsters showed markedly reduced growth and an increase in the expression of keratins K5, K6, K13, and K14. Since our previous work had implicated retinoids in the control of cell adhesiveness, we were interested to rind out whether changes in cell adhesion occur in vitamin A-deficient hamster tracheal epithelial cells, compared to normal cells. Functional assays demonstrated that hamster tracheal epithelial cells, obtained from non-RA-treated tracheas or maintained in culture, displayed reduced attachment to laminin, compared to RA-treated cells. Immunofluorescence studies did not show a decrease either in the alpha6 integrin subunit, which was localized in the basal aspect of basal cells, or in basement membrane laminin. However, the expression of laminin-binding protein 37 decreased as the epithelium changed from pseudostratified to stratified. Therefore, a coordinated pattern of changes in keratin gene expression, as well as in the expression of laminin-binding protein 37, the precursor to the cell surface laminin receptor 67LR, and in adhesive properties takes place in tracheal epithelium when its phenotype changes from mucociliary to the preneoplastic stage of squamous metaplasia. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. OI Darwiche, Nadine/0000-0002-1862-5426 NR 73 TC 41 Z9 41 U1 0 U2 2 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 NOV 15 PY 1992 VL 52 IS 22 BP 6144 EP 6152 PG 9 WC Oncology SC Oncology GA JX754 UT WOS:A1992JX75400002 PM 1384955 ER PT J AU NAKAGAWA, M SCHNEIDER, E DIXON, KH HORTON, J KELLEY, K MORROW, C COWAN, KH AF NAKAGAWA, M SCHNEIDER, E DIXON, KH HORTON, J KELLEY, K MORROW, C COWAN, KH TI REDUCED INTRACELLULAR DRUG ACCUMULATION IN THE ABSENCE OF P-GLYCOPROTEIN (MDR1) OVEREXPRESSION IN MITOXANTRONE-RESISTANT HUMAN MCF-7 BREAST-CANCER CELLS SO CANCER RESEARCH LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; DNA TOPOISOMERASE-II; BACTERIAL TRANSPORT PROTEINS; HL-60 LEUKEMIA-CELLS; MULTIDRUG RESISTANCE; PHASE-II; PLASMA-MEMBRANE; HL60 CELLS; LINE; GENE AB A mitoxantrone-resistant human MCF-7 breast cancer subline (MCF/MX) which is approximately 4000-fold resistant to mitoxantrone was isolated by serial passage of the parental wild-type MCF-7 cells (MCF/WT) in stepwise increasing concentrations of drug. MCF/MX cells were also approximately 10-fold cross-resistant to doxorubicin and etoposide but were not cross-resistant to vinblastine. Intracellular accumulation of radiolabeled mitoxantrone was markedly reduced in MCF/MX cells relative to that in the drug-sensitive MCF/WT cells. This decrease in intracellular drug accumulation into MCF/MX cells was associated with enhanced drug efflux, which was reversed when cells were incubated in the presence of sodium azide and 2, 4-dinitrophenol, suggesting an energy-dependent process. Incubation of MCF/MX cells with verapamil did not affect either the accumulation of mitoxantrone or the level of resistance in these cells. Furthermore, RNase protection and Western blot analyses failed to detect the expression of the mdr1 RNA or P-glycoprotein, a drug efflux pump known to be associated with the development of multidrug resistance in vitro. However, a polyclonal antibody directed against a synthetic peptide corresponding to the putative ATP binding domain of P-glycoprotein reacted with two (M(r) 42,000 and 85,000) membrane proteins from MCF/MX cells which were not found in MCF/WT. Functional assays and Western biot analysis for topoisomerase II revealed no differences in topoisomerase II activity or protein levels in MCF/MX cells. Thus, resistance in this cell line is apparently associated with enhanced drug efflux involving a pathway distinct from the mdr1-encoded multidrug transporter P-glycoprotein. C1 NCI,MED BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892. NR 40 TC 120 Z9 123 U1 0 U2 2 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 NOV 15 PY 1992 VL 52 IS 22 BP 6175 EP 6181 PG 7 WC Oncology SC Oncology GA JX754 UT WOS:A1992JX75400007 PM 1358431 ER PT J AU SILVERS, KJ CHAZINSKI, T MCMANUS, ME BAUER, SL GONZALEZ, FJ GELBOIN, HV MAUREL, P HOWARD, PC AF SILVERS, KJ CHAZINSKI, T MCMANUS, ME BAUER, SL GONZALEZ, FJ GELBOIN, HV MAUREL, P HOWARD, PC TI CYTOCHROME-P-450 3A4 (NIFEDIPINE OXIDASE) IS RESPONSIBLE FOR THE C-OXIDATIVE METABOLISM OF 1-NITROPYRENE IN HUMAN LIVER MICROSOMAL SAMPLES SO CANCER RESEARCH LA English DT Article ID CYCLOSPORINE-A OXIDASE; HAMSTER OVARY CELLS; ADULT HUMAN-LIVER; PRIMARY CULTURES; SALMONELLA-TYPHIMURIUM; EPOXIDE HYDROLASE; HUMAN HEPATOCYTES; DNA ADDUCTS; RAT; ACTIVATION AB The nitrated polycyclic aromatic hydrocarbon 1-nitropyrene is a ubiquitous environmental pollutant. The role of cytochromes P-450 in the human metabolism of [H-3]-1-nitropyrene was investigated using human liver microsomes. The range of microsomal metabolism from 16 individual liver specimens was 0.13 to 0.99 nmol/min/mg protein. Using 3 microsomal samples exhibiting different maximal velocities, the Km of 1-nitropyrene metabolism was 3.3 +/- 0.5 muM, indicating that perhaps a single or similar cytochromes P-450 was involved in the metabolism of 1-nitropyrene in these samples. The P-450 3A inhibitor triacetyloleandomycin inhibited 86 +/- 8% of the microsomal metabolism of 1-nitropyrene. Further evidence for the role of P-450 3A in human microsomal metabolism of 1-nitropyrene was gained using inhibitory anti-P-450 3A antibodies. Using 3 separate microsomal samples, antibody conditions that inhibited approximately 90% of the metabolism of the P-450 3A4-specific substrate nifedipine inhibited approximately 60-70% of the metabolism of 1-nitropyrene. Human liver microsomes demonstrated a preference for 1-nitropyren-3-ol formation over 1-nitropyren-6-ol or 1-nitropyren-8-ol, which is in contrast to that noted in rodents where the 6-ol and 8-ol are preferentially formed over the 3-ol, yet in agreement with earlier studies on the metabolism of 1-nitropyrene using Vaccinia-expressed human cytochromes P-450. These results indicate that the human hepatic metabolism of 1-nitropyrene is carried out by at least two or more P-450s including those in the P-450 3A subfamily. These studies also suggest that the metabolism of this compound by humans may differ from that in rodents in both the cytochromes that are involved and the specific metabolites that are formed. C1 CASE WESTERN RESERVE UNIV, SCH MED, DEPT ENVIRONM HLTH SCI, CLEVELAND, OH 44106 USA. FLINDERS UNIV, MED CTR, DEPT CLIN PHARMACOL, BEDFORD PK, SA 5042, AUSTRALIA. NIH, MOLEC CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. CNRS, INSERM, U128, F-34033 MONTPELLIER, FRANCE. FU NIEHS NIH HHS [ES0648] NR 44 TC 30 Z9 30 U1 1 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 NOV 15 PY 1992 VL 52 IS 22 BP 6237 EP 6243 PG 7 WC Oncology SC Oncology GA JX754 UT WOS:A1992JX75400016 PM 1423267 ER PT J AU SCHOTT, ME MILENIC, DE YOKOTA, T WHITLOW, M WOOD, JF FORDYCE, WA CHENG, RC SCHLOM, J AF SCHOTT, ME MILENIC, DE YOKOTA, T WHITLOW, M WOOD, JF FORDYCE, WA CHENG, RC SCHLOM, J TI DIFFERENTIAL METABOLIC PATTERNS OF IODINATED VERSUS RADIOMETAL CHELATED ANTICARCINOMA SINGLE-CHAIN-FV MOLECULES SO CANCER RESEARCH LA English DT Note ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; CARCINOMA XENOGRAFTS; NUDE-MICE; THERAPY; BINDING; B72.3; GENERATION; FRAGMENTS; PROTEINS; ANTIGEN AB Genetically engineered single-chain Fvs (sFv) are defined as recombinant proteins composed of a variable light chain amino acid sequence of an immunoglobulin tethered to a variable heavy chain sequence by a designed peptide. Previous studies using iodine-labeled sFv, derived from the anticarcinoma monoclonal antibody CC49, showed that the I-125-sFv could efficiently target antigen-positive tumors in a human tumor xenograft model while demonstrating rapid plasma clearance and minimal uptake in normal organs. One of the issues we raised in the analysis of the iodinated sFv metabolic studies was whether similar metabolic patterns would be observed if the sFv were labeled with a radiometal. In the studies reported here, I-125-CC49 sFv and Lu-177-CC49 sFv were coinjected in mice bearing antigen-positive carcinoma xenografts. Both sFv forms showed similar tumor targeting and plasma clearance pharmacokinetics. The Lu-177-sFv, however, showed a greater uptake in liver and spleen and a much higher uptake in kidney. These studies thus demonstrate that despite their small size (M(r) 27,000), the metal-chelated sFv shows a metabolic pattern very different than that of the iodinated sFv, which is most likely due to retention of the metal by organs metabolizing the sFv. C1 NCI,TUMOR IMMUNOL & BIOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. ENZON INC,GAITHERSBURG,MD 20877. DOW CHEM CO USA,MIDLAND,MI 48674. NR 23 TC 74 Z9 76 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 NOV 15 PY 1992 VL 52 IS 22 BP 6413 EP 6417 PG 5 WC Oncology SC Oncology GA JX754 UT WOS:A1992JX75400048 PM 1423290 ER PT J AU ZAHAREVITZ, DW ANDERSON, LW MALINOWSKI, NM HYMAN, R STRONG, JM CYSYK, RL AF ZAHAREVITZ, DW ANDERSON, LW MALINOWSKI, NM HYMAN, R STRONG, JM CYSYK, RL TI CONTRIBUTION OF DENOVO AND SALVAGE SYNTHESIS TO THE URACIL NUCLEOTIDE POOL IN MOUSE-TISSUES AND TUMORS INVIVO SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID PYRIMIDINE BIOSYNTHESIS; ANTITUMOR ACTIVITY; URIDINE; ACID; N-(PHOSPHONACETYL)-L-ASPARTATE; 3-DEAZAURIDINE; DIPYRIDAMOLE; PYRAZOFURIN; NUCLEOSIDES; INHIBITION AB The relative contribution of de-novo and salvage synthesis to tissue pyrimidine nucleotide pools is an important parameter in the rational design of anti-pyrimidine therapies, but has not been measured in vivo. We have measured the contribution of de-novo synthesis to the total acid-soluble uracil nucleotide pool in mouse tissues by analysis of the incorporation of label after intra-peritoneal infusion of L-[N-15]alanine. The contribution of salvage synthesis was measured by the incorporation of radiolabel after intravenous infusion of [C-14]uridine. The results show that de-novo synthesis makes the larger contribution to the intestine uracil nucleotide pool, salvage synthesis makes the larger contribution to the kidney pool, and de-novo and salvage synthesis make roughly equal contributions to the liver pool. In tumors studied (L1210, P388, B16, Nettesheim), the contribution of de-novo synthesis was at least five times the contribution of salvage synthesis. The measurements were repeated 24 hours after a 400-mg/kg dose of N-phosphonacetyl-L-aspartic acid. De-novo synthesis was substantially inhibited in all tissues and tumors after this treatment, although significant residual activity was observed in the intestine and L1210 cells. Nettesheim carcinoma was the only tumor or tissue to show a significant increase in salvage synthesis after N-phosphonacetyl-L-aspartic acid treatment. C1 NCI,DEV THERAPEUT PROGRAM,MED CHEM LAB,DIV CANC TREATMENT,BLDG 37,ROOM 5D-02,BETHESDA,MD 20892. NR 22 TC 15 Z9 15 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD NOV 15 PY 1992 VL 210 IS 1 BP 293 EP 296 DI 10.1111/j.1432-1033.1992.tb17420.x PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KH317 UT WOS:A1992KH31700038 PM 1446677 ER PT J AU LEONARD, D HART, MJ PLATKO, JV EVA, A HENZEL, W EVANS, T CERIONE, RA AF LEONARD, D HART, MJ PLATKO, JV EVA, A HENZEL, W EVANS, T CERIONE, RA TI THE IDENTIFICATION AND CHARACTERIZATION OF A GDP-DISSOCIATION INHIBITOR (GDI) FOR THE CDC42HS PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEIN; BOVINE BRAIN CYTOSOL; SACCHAROMYCES-CEREVISIAE GENE; GUANINE-NUCLEOTIDE EXCHANGE; ACTIVATING PROTEIN; REGULATORY PROTEIN; MOLECULAR-CLONING; PLASMA-MEMBRANES; CELL POLARITY; RAS GTPASE AB The ras-related protein, CDC42Hs, is a 22-kDa GTP-binding protein which is the human homolog of a Saccharomyces cerevisiae yeast-cell-division cycle protein. In attempting to isolate and biochemically characterize mammalian proteins capable of regulating various activities of CDC42Hs, we have identified an activity in bovine brain cytosol which effectively inhibits the dissociation of [H-3]GDP from the platelet- or the Spodoptera frugiperda-expressed CDC42Hs protein. The purification of this activity was achieved by a series of steps which included ammonium sulfate fractionation, DEAE-Sephacel, Mono-Q, and Mono-S chromatographies. The purified CDC42Hs regulatory protein has an apparent molecular weight of 28,000, and cyanogen bromide-generated peptide sequences of this protein were identical to sequences from the carboxyl-terminal portion of rho-GDP-dissociation inhibitor (rho-GDI) (Fukumoto, Y., Kaibuchi, K., Hori, Y., Fujioka, H., Araki, S., Ueda, T., Kikuchi, A., and Takai, Y. (1990) Oncogene 5, 1321-1328). In addition, an Escherichia coli-expressed, glutathione S-transferase-rho-GDI fusion protein fully substitutes for the GDI which we have purified from bovine brain in its ability to inhibit GDP dissociation from CDC42Hs. These findings suggest either that a common regulatory protein (GDI) is capable of inhibiting GDP dissociation from the rho and CDC42Hs proteins or that these two GTP-binding proteins interact with GDI proteins of very similar structure. The purified brain GDI protein shows little ability to inhibit GDP dissociation from the E. coli-expressed CDC42Hs and is capable of only a very weak inhibition of the dissociation of [S-35]guanosine 5'-3-0-(thio)triphosphate (GTPgammaS) from the Spodoptera frugiperda-expressed CDC42. However, brain GDI very effectively inhibits the ability of the human dbl oncogene product to catalyze GDP dissociation from CDC42Hs. In addition to influencing guanine nucleotide association with CDC42Hs, the purified brain GDI protein also appears to catalyze the dissociation of CDC42Hs from the plasma membranes of human placenta and human epidermoid carcinoma (A431) cells. This effect by the GDI protein is observed whether the membrane-associated CDC42Hs is preincubated with GDP, GTPgammaS, or no guanine nucleotides, and occurs over a similar concentration range as that necessary for the inhibition of the intrinsic GDP dissociation. C1 GENENTECH INC,DEPT CELL BIOL & PROT CHEM,S SAN FRANCISCO,CA 94080. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. CORNELL UNIV,DEPT PHARMACOL,ITHACA,NY 14853. RP LEONARD, D (reprint author), CORNELL UNIV,DEPT BIOCHEM MOLEC & CELL BIOL,SCHURMAN HALL,ITHACA,NY 14853, USA. RI Eva, Alessandra/J-8268-2016 OI Eva, Alessandra/0000-0003-2949-078X FU NIGMS NIH HHS [GM47458] NR 46 TC 144 Z9 144 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 NOV 15 PY 1992 VL 267 IS 32 BP 22860 EP 22868 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JY163 UT WOS:A1992JY16300026 PM 1429634 ER PT J AU NATHANSON, MH MOYER, MS BURGSTAHLER, AD OCARROLL, AM BROWNSTEIN, MJ LOLAIT, SJ AF NATHANSON, MH MOYER, MS BURGSTAHLER, AD OCARROLL, AM BROWNSTEIN, MJ LOLAIT, SJ TI MECHANISMS OF SUBCELLULAR CYTOSOLIC CA2+ SIGNALING EVOKED BY STIMULATION OF THE VASOPRESSIN V(1A) RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADRENAL CHROMAFFIN CELLS; INDUCED CALCIUM RELEASE; INOSITOL 1,4,5-TRISPHOSPHATE; INTRACELLULAR CALCIUM; ACINAR-CELLS; OSCILLATIONS; CA-2+; HEPATOCYTES; TRISPHOSPHATE; CHANNELS AB Receptor activation may result in distinct subcellular patterns of Ca2+ release. To define the subcellular distribution of Ca2+i signals induced by stimulation of the vasopressin V1a receptor, we expressed the cloned receptor in Xenopus oocytes. Oocytes were then loaded with fluo-3 and observed using confocal microscopy. Vasopressin induced a single concentric wave of increased Ca2+ that radiated inward from the plasma membrane. With submaximal stimulation, however, regions of the Ca2+ wave spontaneously reorganized into repetitive (oscillatory) waves. Focal stimulation of a small part of the plasma membrane resulted in a Ca2+ wave which began at the point of stimulation, radiated toward the center of the cell, then reorganized into multiple foci of repetitive, colliding waves and spirals of increased Ca2+i. The pattern of Ca2+ signaling induced by foeal or global stimulation was not altered in Ca2+-free medium, although signals did not propagate as fast. Finally, subcellular Ca2+ signaling patterns induced by vasopressin were inhibited by caffeine, while neither vasopressin nor microinjection of inositol trisphosphate blocked caffeine-induced increases in cytosolic Ca2+. Thus, stimulation of the V1a receptor in this cell system induces a complex pattern of Ca2+ signaling which is influenced by (1) the magnitude of the stimulus, (2) the distribution of the surface receptors that are stimulated, and (3) mobilization of Ca2+ from the extracellular space as well as from two distinct endogenous Ca2+ pools. The manner in which a single type of receptor is activated may represent an important potential mechanism for subcellular Ca2+i signaling. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP NATHANSON, MH (reprint author), YALE UNIV,SCH MED,CTR LIVER,LIVER STUDY UNIT,1080 LMP,NEW HAVEN,CT 06510, USA. RI Brownstein, Michael/B-8609-2009 FU NIDDK NIH HHS [P30 DK34989] NR 42 TC 38 Z9 38 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 NOV 15 PY 1992 VL 267 IS 32 BP 23282 EP 23289 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JY163 UT WOS:A1992JY16300088 PM 1429675 ER PT J AU AHMED, SA MILES, EW AF AHMED, SA MILES, EW TI EVIDENCE FOR 2 CONFORMERS OF THE BETA-SUBUNIT OF TRYPTOPHAN SYNTHASE IN SOLUTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE O-SULFATE; ESCHERICHIA-COLI; PYRIDOXAL 5'-PHOSPHATE; SALMONELLA-TYPHIMURIUM; MONOCLONAL-ANTIBODIES; B-PROTEIN; SYNTHETASE; INACTIVATION; MECHANISM; BINDING AB To explain our finding that the dimeric beta subunit of tryptophan synthase is only 50% inactivated by beta-chloro-L-alanine (Ahmed, S. A., Ruvinov, S. B., Kayastha, A. M., and Miles, E. W. (1991) J. Biol. Chem. 266, 21548-21557), we have extended our investigation using spectroscopic, steady-state kinetic, and electrophoretic methods. The spectroscopic properties of the half-active beta2 dimer and the reactivation after alkali treatment show that the inactivation proceeds by an "enamine" mechanism. Although the fully active beta2 dimer associates with the tryptophan synthase alpha subunit to form alpha2beta2 complex, the inactive beta subunits in the half-active enzyme associate weakly or not at all with the alpha subunit. Our results provide evidence for two conformers of the beta subunit in solution: one is rapidly inactivated by beta-chloro-L-alanine and the other is not inactivated. Thermal inactivation studies and non-denaturing polyacrylamide gel electrophoresis of the half-active enzyme show that the beta2 dimer exists in both homologous and heterologous combinations of these two forms. After removal of the reaction products and unreacted beta-chloro-L-alanine from the half-active beta2 dimer by gel filtration, further incubation with beta-chloro-L-alanine results in the loss of 50% of the remaining activity. This result suggests that the subunits undergo rearrangement via an intermediate monomer form to regenerate the two conformers of the active beta subunit. This mechanism of rearrangement is supported by our finding that the extent of inactivation increases at lower concentrations of the beta2 dimer. RP AHMED, SA (reprint author), NIDDKD, BIOCHEM PHARMACOL LAB, BLDG 8, RM 2A-05, BETHESDA, MD 20892 USA. NR 49 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 15 PY 1992 VL 267 IS 32 BP 23309 EP 23317 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JY163 UT WOS:A1992JY16300092 PM 1429678 ER PT J AU SRINIVASAN, AN NAGINENI, CN BHAT, SP AF SRINIVASAN, AN NAGINENI, CN BHAT, SP TI ALPHA-A-CRYSTALLIN IS EXPRESSED IN NONOCULAR TISSUES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LENS CRYSTALLINS; B-CRYSTALLIN; GENE; RAT; PROTEINS; CHAIN; CELLS; DIFFERENTIATION; ASSIGNMENT; SEQUENCE AB Alpha-crystallin, the predominant structural protein of the ocular lens, has been and alphaB-crystallin. Of these two, alphaB-crystallin has been previously shown to be an extralenticular protein while alphaA-crystallin has been considered to be a lens-specific polypeptide. Using an antiserum directed against an N-terminal peptide of alpha-crystallin, we have detected a 20-kDa protein in various rat tissues including the brain, liver, lung, spleen, skin, and small intestine and in a number of established epithelial and fibroblast cell lines. PCR analysis of poly(A)-enriched RNA and Southern blot analysis indicated the presence of alphaA-crystallin mRNA sequences in different non-lenticular tissues. Among the non-ocular tissues examined, spleen showed the highest levels of alphaA-crystallin protein and mRNA. The identity of alphaA-crystallin sequences in the spleen was established by cloning and sequencing a polymerase chain reaction-amplified region of alphaA-crystallin mRNA. Sequences derived from spleen and eye revealed almost 100% identity at the nucleotide level. Interestingly, alphaA-crystallin and alphaB-crystallin seem to exist in an inverse quantitative relationship in the spleen and the heart, the two non-ocular tissues where they show highest concentrations, respectively. The known conserved evolution of alphaA-crystallin and the definitive demonstration of the non-ocular expression of this polypeptide suggest important non-crystallin functions for this protein. C1 UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,100 STEIN PLAZA,RM B118,LOS ANGELES,CA 90024. NIMH,IMMUNOL LAB,BETHESDA,MD 20892. NR 48 TC 211 Z9 214 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 NOV 15 PY 1992 VL 267 IS 32 BP 23337 EP 23341 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JY163 UT WOS:A1992JY16300096 PM 1429679 ER PT J AU CARTER, RS BHAT, NK BASU, A AVADHANI, NG AF CARTER, RS BHAT, NK BASU, A AVADHANI, NG TI THE BASAL PROMOTER ELEMENTS OF MURINE CYTOCHROME-C-OXIDASE SUBUNIT-IV GENE CONSIST OF TANDEMLY DUPLICATED ETS MOTIFS THAT BIND TO GABP-RELATED TRANSCRIPTION FACTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UPSTREAM ACTIVATION SITE; RNA POLYMERASE-II; STRUCTURAL ORGANIZATION; DNA-BINDING; NUCLEOTIDE-SEQUENCE; MITOCHONDRIAL-DNA; NUCLEAR FACTOR; EXPRESSION; PROTEIN; YEAST AB DNA sequences required for expression of the mouse cytochrome c oxidase subunit IV (COXIV) promoter were identified by transient expression of recombinant COXIV-chloramphenicol acetyltransferase constructs in COS and NIH-3T3 cells. Activity of the COXIV promoter is shown to depend upon upstream Sp1 binding sequences and two tandemly repeated 21-base pair sequence elements each mapping to sites of mRNA initiation. Each initiation region repeat contains a binding site for an ets-related transcription factor which demonstrates specificity for the characteristic GGAA ets sequence motif and reactivity with an ets domain-directed monoclonal pan ets antibody. The two 21-base pair repeats are sufficient for transcriptional activity suggesting that the ets-related factor may be involved in both transcriptional activation and start site positioning. The ets-related protein found in COS nuclear extracts is shown to be identical or closely related to the GA-binding protein (GABP) by comparison of electrophoretic mobilities and immunological reactivities of DNA-protein complexes formed with purified recombinant expressed GABP alpha and beta subunits. Sp1 and the GABP-related factors also bind to another mouse cytochrome oxidase subunit gene COXVb. The similar promoter features of these two genes suggests a possible means of coordinate transcriptional regulation among such respiratory proteins. C1 UNIV PENN,SCH VET MED,DEPT ANIM BIOL,BIOCHEM LABS,PHILADELPHIA,PA 19104. NCI,PROGRAM RESOURCES INC,DYNCORP,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,FREDERICK,MD 21702. FU NIGMS NIH HHS [GM-29037] NR 51 TC 73 Z9 73 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 NOV 15 PY 1992 VL 267 IS 32 BP 23418 EP 23426 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JY163 UT WOS:A1992JY16300107 PM 1331086 ER PT J AU KASTURI, S KIHARA, A FITZGERALD, D PASTAN, I AF KASTURI, S KIHARA, A FITZGERALD, D PASTAN, I TI ALANINE SCANNING MUTAGENESIS IDENTIFIES SURFACE AMINO-ACIDS ON DOMAIN-II OF PSEUDOMONAS EXOTOXIN REQUIRED FOR CYTOTOXICITY, PROPER FOLDING, AND SECRETION INTO PERIPLASM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; TOXIN; AERUGINOSA; SITE; DELETION; TOXICITY; PROTEINS; BINDING AB Pseudomonas exotoxin A (PE) is a single polypeptide chain that contains 613 amino acids and is arranged into three major structural domains. Domain la is responsible for cell recognition, domain II for translocation of PE across the membrane, and domain III for ADP-ribosylation of elongation factor 2. Recombinant PE can be produced in Escherichia coli and is efficiently secreted into the periplasm when an OmpA signal sequence is present. To investigate the role of the amino acids located on the surface of domain II in the action of the toxin against mammalian cells, we substituted alanine for each of the 27 surface amino acids present in domain II. Surprisingly, all 27 mutant proteins had some alteration in cytotoxicity when tested on human A431 or MCF7 cells or mouse L929 cells. Native PE has a compact structure and therefore is relatively protease resistant and very little ADP-ribosylation activity is detected in the absence of the denaturing agents like urea and dithiothreitol. Several of the mutations resulted in altered protease sensitivity of the toxin. Seven of the mutant molecules exhibited ADP-ribosylation activity without urea and dithiothreitol, indicating they are partially unfolded. Out of these seven mutants, six had increased cytotoxic activity on at least one of the target cell lines and the other retained its native cytotoxic potency. C1 NCI,DIV CANC BIOL DIAGN & CTR,MOLEC BIOL LAB,BLDG 37,RM 4E16,BETHESDA,MD 20891. NR 20 TC 16 Z9 16 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 NOV 15 PY 1992 VL 267 IS 32 BP 23427 EP 23433 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JY163 UT WOS:A1992JY16300108 PM 1429683 ER PT J AU MORSE, HC AF MORSE, HC TI GENETIC NOMENCLATURE FOR LOCI CONTROLLING SURFACE-ANTIGENS OF MOUSE HEMATOPOIETIC-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Editorial Material ID AFFINITY FC RECEPTOR; T-CELL; MOLECULAR-CLONING; MONOCLONAL-ANTIBODY; MURINE HOMOLOG; NUCLEOTIDE-SEQUENCE; DIFFERENTIATION ANTIGEN; MEMBRANE GLYCOPROTEIN; LYMPHOCYTE-ACTIVATION; TRANSFERRIN RECEPTOR RP MORSE, HC (reprint author), NIAID,IMMUNOPATHOL LAB,BLDG 7,ROOM 304,BETHESDA,MD 20892, USA. NR 85 TC 24 Z9 24 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 NOV 15 PY 1992 VL 149 IS 10 BP 3129 EP 3134 PG 6 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000001 PM 1431091 ER PT J AU NETT, MA CERRETTI, DP BERSON, DR SEAVITT, J GILBERT, DJ JENKINS, NA COPELAND, NG BLACK, RA CHAPLIN, DD AF NETT, MA CERRETTI, DP BERSON, DR SEAVITT, J GILBERT, DJ JENKINS, NA COPELAND, NG BLACK, RA CHAPLIN, DD TI MOLECULAR-CLONING OF THE MURINE IL-1-BETA CONVERTING ENZYME CDNA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENETIC-LINKAGE MAP; INTERLEUKIN-1; ACID; DNA; EXPRESSION; IL-1-ALPHA; SEQUENCE; PROTEASE; CLONES; IL-1 AB IL-1beta is a potent modulator of immune and inflammatory responses. Murine IL-1beta is initially synthesized as an inactive 33-kDa pro-molecule that is activated by proteolytic cleavage between Asp-117 and Val-118 to generate the 17-kDa mature IL-1beta protein. This cleavage is catalyzed by a specific protease that has been designated the IL-1beta converting enzyme (or IL-1beta convertase). We have used a human IL-1beta convertase cDNA to isolate murine convertase cDNA from a WEHI-3 library. These cDNA predicted that the murine convertase is a 402-residue protein. Overall, the murine convertase showed 71% nucleotide and 62% predicted amino acid sequence identity with the human convertase. Southern blot analysis of interspecific backcross mice indicated that the murine IL-1beta convertase is encoded by a single copy gene located on murine chromosome 9. The murine convertase showed broad constitutive expression, being detected in mononuclear phagocyte and T lymphocyte cell lines as well as in spleen, heart, brain, and adrenal glands. The expression of the murine convertase in mononuclear phagocytes was up-regulated by treatment with LPS or rIFN-gamma. These studies establish that the IL-1beta convertase is an evolutionarily conserved, widely expressed enzyme that can be regulated at a pretranslational level. C1 WASHINGTON UNIV,SCH MED,HOWARD HUGHES MED INST,4566 SCOTT AVE,BOX 8022,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,DIV ALLERGY & IMMUNOL,ST LOUIS,MO 63110. IMMUNEX CORP,DEPT MOLEC BIOL,SEATTLE,WA 98101. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. IMMUNEX CORP,DEPT PROT CHEM,SEATTLE,WA 98101. FU NCI NIH HHS [N01-CO-74101] NR 26 TC 73 Z9 74 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1992 VL 149 IS 10 BP 3254 EP 3259 PG 6 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000017 PM 1431103 ER PT J AU NEWMAN, MA MAINHART, CR MALLETT, CP LAVOIE, TB SMITHGILL, SJ AF NEWMAN, MA MAINHART, CR MALLETT, CP LAVOIE, TB SMITHGILL, SJ TI PATTERNS OF ANTIBODY SPECIFICITY DURING THE BALB/C IMMUNE-RESPONSE TO HEN EGG-WHITE LYSOZYME SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; TOPOGRAPHIC ANTIGENIC DETERMINANTS; B-CELL REPERTOIRE; MONOCLONAL-ANTIBODIES; 3-DIMENSIONAL STRUCTURE; SOMATIC HYPERMUTATION; AVIAN LYSOZYME; DIVERSITY; MATURATION; SITES AB We tested 49 BALB/c antilysozyme mAb from seven intervals during the immune response to lysozyme for patterns of specificity and avidity. We found that the antibody epitopes in composite covered at least 80% of the lysozyme surface, and their patterns of overlap suggest a continuum of potential antibody epitopes. Previously observed regional specificities, which emerged at different times in the immune response, were more discretely defined in late response antibodies, when the majority of mAb could be assigned to one of three functionally nonoverlapping complementation groups. The area covered by each antigenic region may be greater than an individual epitope, and may include multiple epitopes that overlap structurally and functionally to varying degrees. Connectivity between antigenic regions was seen in interactions among early and late stage antibodies, and among secondary stage mAb, but not among tertiary stage mAb from hyperimmunized mice. Patterns of overlap of early and late response antibodies suggest that the organization of antibody specificities change during the progression from primary to secondary to tertiary response. Over the same period in the response, the average relative avidity of IgG1kappa mAb did not increase, suggesting that "affinity maturation" of serum antibodies reflects an increase in the number and diversity of antibodies, rather than an overall increase in the avidity of individual antibodies. C1 NCI,GENET LAB,BLDG 37,ROOM 2B10,BETHESDA,MD 20892. UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20742. NR 80 TC 72 Z9 74 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 NOV 15 PY 1992 VL 149 IS 10 BP 3260 EP 3272 PG 13 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000018 PM 1431104 ER PT J AU CONLON, KC OCHOA, AC KOPP, WC ORTALDO, JR URBA, WJ LONGO, DL YOUNG, HA AF CONLON, KC OCHOA, AC KOPP, WC ORTALDO, JR URBA, WJ LONGO, DL YOUNG, HA TI ENHANCED LYMPHOKINE PRODUCTION AND LYMPHOKINE RECEPTOR EXPRESSION IN MULTIPLE ANTIBODY-STIMULATED HUMAN CD4+ PERIPHERAL-BLOOD LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; CROSS-LINKING; PROLIFERATIVE RESPONSE; MONOCLONAL-ANTIBODIES; MEDIATED ACTIVATION; ACCESSORY MOLECULE; FACTOR-ALPHA; INTERLEUKIN-2 AB Treatment of T lymphocytes with antibodies directed against the T cell receptor CD3 complex results in cellular activation that can be augmented by costimulation through other cell surface receptors. The activities of anti-CD3-stimulated human CD4+ PBL were compared to anti-CD3 plus anti-CD2-, anti-CD4-, or anti-CD11a (LFA-1)-stimulated cells. [H-3]thymidine incorporation, lymphokine receptor expression, expansion of cell numbers, and lymphokine mRNA and protein were measured. Forty-eight hours after activation, costimulated CD4+ cells demonstrated increased numbers of cells positive for surface IL-2R alpha-chain, IL-2R beta-chain, IFN-gamma receptors, and TNF-alpha receptors. By day 6, costimulated cells exhibited a sevenfold greater expansion in cell numbers compared to cells stimulated with anti-CD3 alone. Anti-CD3 plus anti-CD11a stimulation consistently induced the highest secretion of IL-2 and IFN-gamma, whereas variation in secretion of TNF-alpha and IL-4 between different donors was noted. Analysis of lymphokine receptor mRNA demonstrated increased levels of mRNA for IL-2R alpha-chain and IFN-gamma receptor that preceded the phenotypic changes on the cell surface. In contrast, levels of IL-2R beta-chain and the TNF-alpha receptor mRNA decreased after stimulation. Amounts of IL-2, IL-4, and TNF-alpha, but not IFN-gamma, secreted also correlated with the levels of mRNA measured in the cells. Although costimulation through CD2, CD4, or LFA-1 appeared equally effective for the induction of the lymphokine receptors, these additional stimuli had a different impact on lymphokine secretion. These results indicate that specific control of lymphokine secretion and receptor induction can be another function of the CD2, CD4, and CD11a cell surface receptors. This control is evident at both transcriptional and post-transcriptional levels. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CLIN SERV PROGRAM,FREDERICK,MD 21702. RP CONLON, KC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,BLDG 560,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 48 TC 15 Z9 15 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 NOV 15 PY 1992 VL 149 IS 10 BP 3278 EP 3289 PG 12 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000020 PM 1358968 ER PT J AU COX, GW MELILLO, G CHATTOPADHYAY, U MULLET, D FERTEL, RH VARESIO, L AF COX, GW MELILLO, G CHATTOPADHYAY, U MULLET, D FERTEL, RH VARESIO, L TI TUMOR NECROSIS FACTOR-ALPHA-DEPENDENT PRODUCTION OF REACTIVE NITROGEN INTERMEDIATES MEDIATES IFN-GAMMA PLUS IL-2-INDUCED MURINE MACROPHAGE TUMORICIDAL ACTIVITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IL-2 RECEPTOR EXPRESSION; HUMAN-MONOCYTES; NITRIC-OXIDE; INTERFERON-GAMMA; INTERLEUKIN-2 RECEPTOR; PERITONEAL-MACROPHAGES; KILLING MECHANISM; CYTO-TOXICITY; CELLS; INDUCTION AB We have previously established that IFN-gamma plus IL-2 induces murine macrophage tumoricidal activity. The purpose of this study was to identify the effector molecules that account for the IFN-gamma plus IL-2-induced macrophage cytotoxicity against P815 mastocytoma cells. ANA-1 macrophages and normal thioglycollate-elicited mouse peritoneal macrophages produced little or no detectable nitrite (NO2-) after incubation with IFN-gamma alone or IL-2 alone; however, IL-2 synergized with IFN-gamma for the production of NO2-. IFN-gamma plus IL-2 did not induce NO2- production or tumoricidal activity in ANA-1 macrophages that were cultured in medium devoid of L-arginine or in ANA-1 macrophages that were incubated with N(G)-monomethyl-L-arginine. As observed previously with ANA-1 macrophage tumoricidal activity, IL-4 inhibited IFN-gamma plus IL-2-induced, but not IFN-gamma plus LPS-induced, NO2- production. IL-4 also selectively decreased the ability of IFN-gamma and/or IL-2 to augment TNF-alpha mRNA expression in ANA-1 macrophages. Lastly, incubation of ANA-1 macrophages with anti-TNF mAb selectively inhibited the ability of IFN-gamma plus IL-2 to induce NO2- production and tumoricidal activity. These results indicate that IFN-gamma plus IL-2-induced tumoricidal activity is dependent upon the metabolism of L-arginine to reactive nitrogen intermediates, and they establish a role for TNF-alpha as a required intermediate for IL-2-dependent NO2- production and tumoricidal activity. C1 OHIO STATE UNIV,COLL MED,DEPT PHARMACOL,COLUMBUS,OH 43210. RP COX, GW (reprint author), NCI,FREDERICK CANC RES DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 43 TC 140 Z9 144 U1 1 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 NOV 15 PY 1992 VL 149 IS 10 BP 3290 EP 3296 PG 7 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000021 PM 1431106 ER PT J AU NATH, J OHNO, Y GALLIN, JI WRIGHT, DG AF NATH, J OHNO, Y GALLIN, JI WRIGHT, DG TI A NOVEL POSTTRANSLATIONAL INCORPORATION OF TYROSINE INTO MULTIPLE PROTEINS IN ACTIVATED HUMAN NEUTROPHILS - CORRELATION WITH PHAGOCYTOSIS AND ACTIVATION OF THE NADPH OXIDASE-MEDIATED RESPIRATORY BURST SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; PHORBOL-MYRISTATE ACETATE; CHRONIC GRANULOMATOUS-DISEASE; TUBULIN TYROSINOLATION; CYTOCHROME-B; SUPEROXIDE RELEASE; ALPHA-TUBULIN; CYTOPLASTS; FERTILIZATION; CELLS AB Activation of human neutrophils by PMA causes a post-translational incorporation of C-14-labeled tyrosine into multiple neutrophil (PMN) proteins, that is distinctly different from the enzymatic tyrosinolation of tubulin in FMLP-stimulated PMN. Post-translational incorporation of other radiolabeled amino acids, including the structurally similar amino acid phenylalanine, does not occur under identical conditions of neutrophil activation, suggesting an involvement of the phenolic hydroxyl group of tyrosine in the PMA-mediated reaction. Similar to the stimulation of PMN tubulin tyrosinolation by FMLP, the PMA-induced incorporation of tyrosine into multiple PMN proteins is closely associated with activation of the NADPH oxidase-mediated respiratory burst in stimulated PMN and can be inhibited by a variety of reducing agents, inhibitors of peroxidase-mediated reactions, and intracellular scavengers of oxygen radicals. Moreover, the PMA-induced post-translational incorporation of tyrosine does not occur in PMN from patients with chronic granulomatous disease and is significantly reduced (50%) in PMN of an individual with myeloperoxidase deficiency. A similar stimulus-induced incorporation of tyrosine into multiple PMN proteins is also observed in PMN exposed to various phagocytic stimuli, and the incorporated radioactivity in cells undergoing phagocytosis is substantially enriched (40- to 50-fold) in isolated PMN phagolysosomes. Consistent with this latter observation, HPLC fractionation of stimulated PMN proteins and analysis of the incorporated radioactivity reveal that the C-14 label is primarily associated with PMN membrane proteins. Furthermore, this post-translational incorporation of tyrosine, like that associated with PMA stimulation, is associated with production of oxygen radicals and the generation of protein carbonyl derivatives, which are indicative of oxidative protein modifications via mixed function oxidases. Our findings indicate that tyrosine incorporation into membrane proteins of stimulated PMN is functionally relevant to the physiologic host-defense responses of human neutrophils undergoing phagocytosis. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. RP NATH, J (reprint author), WALTER REED ARMY INST RES,DEPT HEMATOL,DIV MED,WASHINGTON,DC 20307, USA. NR 42 TC 6 Z9 6 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 NOV 15 PY 1992 VL 149 IS 10 BP 3360 EP 3371 PG 12 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000032 PM 1331234 ER PT J AU MAGE, MG LEE, L RIBAUDO, RK CORR, M KOZLOWSKI, S MCHUGH, L MARGULIES, DH AF MAGE, MG LEE, L RIBAUDO, RK CORR, M KOZLOWSKI, S MCHUGH, L MARGULIES, DH TI A RECOMBINANT, SOLUBLE, SINGLE-CHAIN CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE WITH BIOLOGICAL-ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE H-2D(D); BETA(2)2-MICROGLOBULIN; ANTIGEN PRESENTATION ID SURFACE EXPRESSION; MHC MOLECULES; LYMPHOCYTES-T; CELL-SURFACE; HEAVY-CHAIN; BETA-2-MICROGLOBULIN; PEPTIDES; ANTIGEN; BINDING; DOMAINS AB Heterodimeric class I major histocompatibility complex molecules, which consist of a 45-kDa heavy-chain and a 12-kDa beta2-microglobulin (beta2m) light chain, bind endogenously synthesized peptides for presentation to antigen-specific T cells. We have synthesized a gene encoding a single-chain, soluble class I molecule derived from mouse H-2D(d), in which the carboxyl terminus of beta2m is linked via a peptide spacer to the amino terminus of the heavy chain. The chimeric protein is secreted efficiently from transfected L cells, is thermostable, and when loaded with an appropriate antigenic peptide, stimulates an H-2D(d)-restricted antigen-specific T-cell hybridoma. Thus, functional binding of peptide does not require the complete dissociation of beta2m, implying that a heavy chain/peptide complex is not an obligate intermediate in the assembly of the heavy-chain/beta2m/peptide heterotrimer. Single-chain major histocompatibility complex molecules uniformly loaded with peptide have potential uses for structural studies, toxin or fluor conjugates, and vaccines. C1 NIAID,IMMUNOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. RP MAGE, MG (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 39 TC 39 Z9 40 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 10658 EP 10662 DI 10.1073/pnas.89.22.10658 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400020 PM 1438262 ER PT J AU PAOLINI, R NUMEROF, R KINET, JP AF PAOLINI, R NUMEROF, R KINET, JP TI PHOSPHORYLATION DEPHOSPHORYLATION OF HIGH-AFFINITY IGE RECEPTORS - A MECHANISM FOR COUPLING UNCOUPLING A LARGE SIGNALING COMPLEX SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL ANTIGEN RECEPTOR; PROTEIN-TYROSINE KINASE; BASOPHILIC LEUKEMIA-CELLS; T-CELL; IMMUNOGLOBULIN-E; FC-RECEPTORS; ACTIVATION; STIMULATION; TRANSDUCTION; ANTIBODY AB Engagement of high-affinity IgE receptors leads to activation of tyrosine and serine/threonine kinases and the immediate phosphorylation of receptor beta (serine and tyrosine) and gamma (threonine and tyrosine) chains. Receptor disengagement leads to dephosphorylation of beta and gamma chains via the action of undefined phosphatases. Here we have identified five distinct polypeptides associated with the high-affinity IgE-receptor tetrameric complex, which apparently become phosphorylated and dephosphorylated in sequence with the beta and gamma chains. Like beta chain, polypeptides pp180, pp48, pp42, and pp28 are phosphorylated on serine and tyrosine, whereas pp125 is only phosphorylated on serine. The phosphorylation of each of these receptor-associated polypeptides is antigen-dose dependent and is restricted to activated receptor complexes. Furthermore the physical association between pp125 and the receptor is quantitatively affected by receptor phosphorylation and dephosphorylation, indicating a coupling-uncoupling mechanism. Finally, in vitro kinase experiments show that activated receptor complexes are also physically associated with tyrosine and serine/threonine kinases as part of a larger complex containing the phosphorylated polypeptides. RP PAOLINI, R (reprint author), NIAID,TWINBROOK II BLDG,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 34 TC 56 Z9 56 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 10733 EP 10737 DI 10.1073/pnas.89.22.10733 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400036 PM 1438270 ER PT J AU TAKAHASHI, N BREITMAN, TR AF TAKAHASHI, N BREITMAN, TR TI COVALENT MODIFICATION OF PROTEINS BY LIGANDS OF STEROID-HORMONE RECEPTORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HL-60 CELLS; RETINOIC ACID ID CELL-LINE HL-60; ACUTE PROMYELOCYTIC LEUKEMIA; TRANS RETINOIC ACID; RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; THYROID-HORMONE; 1,25-DIHYDROXYVITAMIN D3; EMBRYONAL CARCINOMA; CANCER-CELLS; DIFFERENTIATION; BINDING AB Retinoylation, acylation with retinoic acid (RA), is a covalent modification of proteins occurring in a variety of eukaryotic cell lines. In this study, we found that proteins in HL-60 cells were labeled by 17beta-[H-3]estradiol (E2), [H-3]progesterone (Pg), 1alpha,25-dihydroxy[H-3]vitamin D3 11,25(OH)2D3], [I-125]triiodothyronine (T3), [I-125]thyroxine (T4), and [H-3]prostaglandin E2 (PGE2). All of these hormones, except PGE2, are ligands of the steroid hormone receptor family. Addition to the growth medium of 5 muM ketoconazole, an inhibitor of cytochrome P450-dependent enzymes, increased about 2-fold the labeling of proteins by T3, T4, 1,25(OH)2D3, and PGE2. In contrast, ketoconazole did not change markedly the extent of labeling by RA, E2, or Pg. Alkaline methanolysis, which cleaves ester bonds, released variable percentages of the radioactive ligands bound to protein. These values were about 80% for RA and PGE2; 50% for T3, T4, and Pg; and 20% for E2 and 1,25(OH)2D3. Treatment with thioether-cleavage reagents, iodomethane or Raney nickel catalyst, released <2% of the covalently bound ligands. Two-dimensional polyacrylamide gel electrophoresis patterns of labeled proteins were unique for each ligand. Proteins of M(r) 47,000 and 51,000 were labeled by RA, E2, T3, and T4. These proteins had the same mobilities as RI and RII, the cAMP-binding regulatory subunits of type I and type II cAMP-dependent protein kinases. 1,25(OH)2D3 also bound to proteins of M(r) 47,000 and 51,000. However, these proteins had pl values different from those of RI or RII. These results suggest that some activities of ligands of the steroid hormone receptor family and of PGE2 may be mediated by their covalent modification of proteins. RP TAKAHASHI, N (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892, USA. NR 69 TC 19 Z9 19 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 10807 EP 10811 DI 10.1073/pnas.89.22.10807 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400051 PM 1438281 ER PT J AU SUTTER, G MOSS, B AF SUTTER, G MOSS, B TI NONREPLICATING VACCINIA VECTOR EFFICIENTLY EXPRESSES RECOMBINANT GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE POXVIRUS; EXPRESSION VECTOR; ATTENUATION; HOST RESTRICTION ID HUMAN-CELLS; VIRUS MVA; VIRULENCE; PROTEIN; DELETION; SEQUENCE; MORPHOGENESIS; SELECTION; GENOME AB Modified vaccinia Ankara (MVA), a highly attenuated vaccinia virus strain that has been safety tested in humans, was evaluated for use as an expression vector. MVA has multiple genomic deletions and is severely host cell restricted: it grows well in avian cells but is unable to multiply in human and most other mammalian cells tested. Nevertheless, we found that replication of viral DNA appeared normal and that both early and late viral proteins were synthesized in human cells. Proteolytic processing of viral structural proteins was inhibited, however, and only immature virus particles were detected by electron microscopy. We constructed an insertion plasmid with the Escherichia coli lacZ gene under the control of the vaccinia virus late promoter P11, flanked by sequences of MVA DNA, to allow homologous recombination at the site of a naturally occurring 3500-base-pair deletion within the MVA genome. MVA recombinants were isolated and propagated in permissive avian cells and shown to express the enzyme beta-galactosidase upon infection of nonpermissive human cells. The amount of enzyme made was similar to that produced by a recombinant of vaccinia virus strain Western Reserve, which also had the lacZ gene under control of the P11 promoter, but multiplied to high titers. Since recombinant gene expression is unimpaired in nonpermissive human cells, MVA may serve as a highly efficient and exceptionally safe vector. RP SUTTER, G (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 39 TC 450 Z9 455 U1 3 U2 6 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 10847 EP 10851 DI 10.1073/pnas.89.22.10847 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400059 PM 1438287 ER PT J AU HELLMICH, MR PANT, HC WADA, E BATTEY, JF AF HELLMICH, MR PANT, HC WADA, E BATTEY, JF TI NEURONAL CDC2-LIKE KINASE - A CDC2-RELATED PROTEIN-KINASE WITH PREDOMINANTLY NEURONAL EXPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHOSPHORYLATION; INTERMEDIATE FILAMENT; NEUROFILAMENT; CELL CYCLE ID CDC2 KINASE; PHOSPHORYLATION; CYCLIN; YEAST; GENE AB Recent studies have shown that there exists a family of protein kinases structurally and functionally related to the yeast cell cycle regulatory kinase cdc2 [Meyerson, M., Faha, B., Su, L.-K., Harlow, E. & Tsai, L.-H. (1991) Cold Spring Harbor Symp. Quant. Biol. 56, 177-186 and Meyerson, M., Enders, G. H., Wu, C.-L., Su, L.-K., Gorka, C., Nelson, C., Harlow, E. & Tsai, L.-H. (1992) EMBO J. 11, 2909-2917]. Two members of cdc2 family, p34cdc2 (also named cdk1) and cdk2, have been identified in mammalian cells. cdk1 kinase regulates the progression from G2 to M phase, and cdk2 kinase has been proposed to regulate the progression from G1 to S phase. In this work, we have cloned and structurally characterized a third member of the cdc2 kinase family with 58% amino acid sequence identity to mouse cdk1 and 61% identity to human cdk2. We call this kinase neuronal cdc2-like kinase (nclk) because, in contrast to either cdk1 or cdk2, nclk is expressed at high levels in terminally differentiated neurons no longer in the cell cycle. Previous studies have shown [Hisanaga, S., Kusubata, M., Okumura, E. & Kishimoto, T. (1991) J. Biol. Chem. 266, 21798-21803 and Guan, R. J., Hall, F. L. & Cohlberg, J. A. (1992) J. Neurochem. 58, 1365-1371] that cdk1 kinase, but not other structurally defined protein kinases, could phosphorylate the repeated Lys-Ser-Pro (KSP) motifs found in mammalian high and middle molecular mass neurofilament subunits in vitro, but the precise molecular nature of the endogenous neuronal KSP kinase has remained undefined. The structural similarity of nclk to cdk1 kinase and its high level of expression in terminally differentiated neurons suggest that nclk may play a role in the phosphorylation of the neurofilament KSP repeats in vivo, a function distinct from cell cycle regulation. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BLDG 37,ROOM 5D02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NR 23 TC 238 Z9 244 U1 1 U2 5 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 10867 EP 10871 DI 10.1073/pnas.89.22.10867 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400063 PM 1279696 ER PT J AU DALY, JW CACERES, J MONI, RW GUSOVSKY, F MOOS, M SEAMON, KB MILTON, K MYERS, CW AF DALY, JW CACERES, J MONI, RW GUSOVSKY, F MOOS, M SEAMON, KB MILTON, K MYERS, CW TI FROG SECRETIONS AND HUNTING MAGIC IN THE UPPER AMAZON - IDENTIFICATION OF A PEPTIDE THAT INTERACTS WITH AN ADENOSINE RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article AB A frog used for "hunting magic" by several groups of Panoan-speaking Indians in the borderline between Brazil and Peru is identified as Phyllomedusa bicolor. This frog's skin secretion, which the Indians introduce into the body through fresh burns, is rich in peptides. These include vasoactive peptides, opioid peptides, and a peptide that we have named adenoregulin, with the sequence GLWSKIKEVGKEAAKAAAKAAGKAALGAVSEAV as determined from mass spectrometry and Edman degradation. The natural peptide may contain a D amino acid residue, since it is not identical in chromatographic properties to the synthetic peptide. Adenoregulin enhances binding of agonists to A1 adenosine receptors; it is accompanied in the skin secretion by peptides that inhibit binding. The vasoactive peptide sauvagine, the opioid peptides, and adenoregulin and related peptides affect behavior in mice and presumably contribute to the behavioral sequelae observed in humans. C1 US FDA,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. UNIV CALIF BERKELEY,DEPT ANTHROPOL,BERKELEY,CA 94720. AMER MUSEUM NAT HIST,DEPT HERPETOL & ICHTHYOL,NEW YORK,NY 10024. RP DALY, JW (reprint author), NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 14 TC 85 Z9 90 U1 0 U2 14 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 10960 EP 10963 DI 10.1073/pnas.89.22.10960 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400082 PM 1438301 ER PT J AU ERICKSON, JD EIDEN, LE HOFFMAN, BJ AF ERICKSON, JD EIDEN, LE HOFFMAN, BJ TI EXPRESSION CLONING OF A RESERPINE-SENSITIVE VESICULAR MONOAMINE TRANSPORTER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE VACCINIA VIRUS; TRANSFECTION; BIOGENIC AMINE UPTAKE; DIGITONIN PERMEABILIZATION; PHOTOAFFINITY LABELING ID BOVINE CHROMAFFIN GRANULES; SYNAPTIC VESICLES; DOPAMINE TRANSPORTER; CATECHOLAMINE TRANSPORTER; SEROTONIN TRANSPORTER; HUMAN-FIBROBLASTS; STORAGE-VESICLES; RAT-BRAIN; MEMBRANE; ACCUMULATION AB A cDNA for a rat vesicular monoamine transporter, designated MAT, was isolated by expression cloning in a mammalian cell line (CV-1). The cDNA sequence predicts a protein of 515 amino acids with 12 putative membrane-spanning domains. The characteristics of [H-3]serotonin accumulation by CV-1 cells expressing the cDNA clone suggested sequestration by an intracellular compartment. In cells permeabilized with digitonin, uptake was ATP dependent with an apparent K(m) of 1.3 muM. Uptake was abolished by the proton-translocating ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone and with tri-(n-butyl)tin, an inhibitor of the vacuolar H+-ATPase. The rank order of potency to inhibit uptake was reserpine > tetrabenazine > serotonin > dopamine > norepinephrine > epinephrine. Direct comparison of [H-3]monoamine uptake indicated that serotonin was the preferred substrate. Photolabeling of membranes prepared from CV-1 cells expressing MAT with 7-azido-8-[I-125]iodoketanserin revealed a predominant tetrabenazine-sensitive photolabeled glycoprotein with an apparent molecular mass of almost-equal-to 75 kDa. The mRNA that encodes MAT was present specifically in monoamine-containing cells of the locus coeruleus, substantia nigra, and raphe nucleus of rat brain, each of which expresses a unique plasma membrane reuptake transporter. The MAT cDNA clone defines a vesicular monoamine transporter representing a distinct class of neurotransmitter transport molecules. C1 NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892. OI Eiden, Lee/0000-0001-7524-944X NR 48 TC 389 Z9 394 U1 1 U2 5 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 10993 EP 10997 DI 10.1073/pnas.89.22.10993 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400089 PM 1438304 ER PT J AU MARVIN, KW GEORGE, MD FUJIMOTO, W SAUNDERS, NA BERNACKI, SH JETTEN, AM AF MARVIN, KW GEORGE, MD FUJIMOTO, W SAUNDERS, NA BERNACKI, SH JETTEN, AM TI CORNIFIN, A CROSS-LINKED ENVELOPE PRECURSOR IN KERATINOCYTES THAT IS DOWN-REGULATED BY RETINOIDS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; TRACHEAL EPITHELIAL-CELLS; TRANSGLUTAMINASE ACTIVITY; SQUAMOUS DIFFERENTIATION; MAMMALIAN EPIDERMIS; PROTEINS; EXPRESSION; ACID; GENE; INVOLUCRIN AB In this study, we have characterized the cDNA clone SQ37 that was isolated previously from a rabbit squamous cell library. The gene encodes a 14-kDa protein that appears to function as a component of the cross-linked envelope in squamous differentiating cells. The protein, which has been named cornifin, has a high content of proline (31%), glutamine (20%), and cysteine (11%) and contains 13 repeats of an octapeptide (consensus sequence, EPCQPKVP) at its C terminus. SQ37 mRNA and protein are induced during squamous differentiation of rabbit tracheal (RbTE) cells and human epidermal keratinocytes. This induction is repressed by retinoids. Immunohistochemical studies reveal SQ37 immunoreactivity in fragmented cross-linked envelopes from squamous-differentiated RbTE cells and in the suprabasal layers of the epidermis. In situ hybridization analysis showed that the presence of SQ37 mRNA is restricted to the suprabasal layers. Treatment of RbTE cells with a Ca2+ ionophore induces cross-linking of the SQ37 protein into higher molecular weight complexes. This cross-linking reaction appears to be mediated by transglutaminase type I. Our observations suggest that the protein encoded by SQ37 participates in the assembly of the cross-linked envelope. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. RI saunders, nicholas/E-1544-2014; McTaggart, Jill/G-4696-2010; OI saunders, nicholas/0000-0002-2478-3420; McTaggart, Jill/0000-0002-9000-8529; Jetten, Anton/0000-0003-0954-4445 NR 39 TC 146 Z9 148 U1 0 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 11026 EP 11030 DI 10.1073/pnas.89.22.11026 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400096 PM 1438308 ER PT J AU OLLER, AR FIJALKOWSKA, IJ DUNN, RL SCHAAPER, RM AF OLLER, AR FIJALKOWSKA, IJ DUNN, RL SCHAAPER, RM TI TRANSCRIPTION-REPAIR COUPLING DETERMINES THE STRANDEDNESS OF ULTRAVIOLET MUTAGENESIS IN ESCHERICHIA-COLI SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MUTATION FREQUENCY DECLINE; PREFERENTIAL DNA-REPAIR; HUMAN-DIPLOID FIBROBLASTS; UV-INDUCED MUTATION; EXCISION-REPAIR; PYRIMIDINE DIMERS; HUMAN-CELLS; LACI GENE; DIFFERENTIAL REPAIR; ACTIVE GENE AB We have analyzed the spectra of UV-induced mutations in the lacI gene of a wild-type and an mfd strain of Escherichia coli. mfd strains have been recently proposed to be deficient in a factor coupling DNA repair and transcription. Analysis of UV-induced mutations occurring at adjacent pyrimidines showed that mutations in the wild-type strain arose largely from the nontranscribed strand but arose predominantly from the transcribed strand in the mfd strain. The overall strand switch was 14-fold. One mutation, G.C --> A.T in the lacI initiation codon, showed a >300 -fold shift. No effect was observed for mutations at non-pyrimidine-pyrimidine sequences. These results provide in vivo evidence for a key role of the mfd gene in controlling the strandedness of mutagenesis and support the proposed role of the mfd gene product in directing DNA excision repair to the transcribed strand of a damaged gene. RP OLLER, AR (reprint author), NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Fijalkowska, Iwona/I-7796-2016 NR 47 TC 71 Z9 71 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 11036 EP 11040 DI 10.1073/pnas.89.22.11036 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400098 PM 1438310 ER PT J AU POLLI, JW KINCAID, RL AF POLLI, JW KINCAID, RL TI MOLECULAR-CLONING OF DNA ENCODING A CALMODULIN-DEPENDENT PHOSPHODIESTERASE ENRICHED IN STRIATUM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CYCLIC NUCLEOTIDES; BASAL GANGLIA; DOPAMINE ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; BOVINE BRAIN; RAT-BRAIN; CGMP PHOSPHODIESTERASE; EXPRESSION; ISOZYMES; IDENTIFICATION; INHIBITORS; SEQUENCE; HOMOLOGS AB A murine cDNA for the 63-kDa calmodulin-dependent phosphodiesterase (CaM-PDE), PDE1B-1, was isolated by using polymerase chain reaction with degenerate primers followed by the cloning of a full-length cDNA from a whole-brain phage library. The nucleotide sequence of 2986 base pairs contains an open reading frame encoding a protein of 535 amino acids (M(r) = 61,231) with a predicted isoelectric point of 5.54. The deduced protein sequence shows almost-equal-to 60% identity with that of the 61-kDa isoform (PDE1A2), consistent with the proposal that these proteins arise from two separate genes [Novack, J. P., Charbonneau, H., Bentley, J. K., Walsh, K. A. & Beavo, J. A. (1991) Biochemistry 30, 7940-7947]. Southern blot analysis suggests high nucleotide-sequence conservation of the PDE1B1 gene among mammalian and avian species. A single almost-equal-to 3600-nucleotide mRNA transcript was seen in all brain regions, with striatum containing 4- to 30-fold higher levels than other areas. In nonneural tissues, low amounts of PDE1B1 mRNA were detected in lung, spleen, thymus, and testis; hybridization to several larger mRNA species was also seen in thymus and testis. By using nucleic acid probes for PDE1B1, the mechanisms that control its highly selective gene expression can now be studied at the molecular level. RP POLLI, JW (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,IMMUNOL SECT,ROCKVILLE,MD 20852, USA. NR 32 TC 52 Z9 53 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 11079 EP 11083 DI 10.1073/pnas.89.22.11079 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400107 PM 1332068 ER PT J AU YUSUF, S PEPINE, CJ GARCES, C POULEUR, H SALEM, D KOSTIS, J BENEDICT, C ROUSSEAU, M BOURASSA, M PITT, B AF YUSUF, S PEPINE, CJ GARCES, C POULEUR, H SALEM, D KOSTIS, J BENEDICT, C ROUSSEAU, M BOURASSA, M PITT, B TI EFFECT OF ENALAPRIL ON MYOCARDIAL-INFARCTION AND UNSTABLE ANGINA IN PATIENTS WITH LOW EJECTION FRACTIONS SO LANCET LA English DT Article ID CORONARY HEART-DISEASE; CONVERTING ENZYME-INHIBITION; RANDOMIZED CLINICAL-TRIALS; BLOOD-PRESSURE; PRIMARY-PREVENTION; ANGIOTENSIN-II; FAILURE; STROKE; RISK; HYPERTENSION AB An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions less-than-or-equal-to 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% Cl 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% Cl 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions. C1 NHLBI,BETHESDA,MD 20892. UNIV FLORIDA,GAINESVILLE,FL 32611. UNIV N CAROLINA,CHAPEL HILL,NC 27514. NEW ENGLAND MED CTR,BOSTON,MA 02111. UNIV TEXAS,MED CTR,HOUSTON,TX 77025. UNIV MICHIGAN,ANN ARBOR,MI 48109. ROBERT WOOD JOHNSON MED CTR,NEW BRUNSWICK,NJ. UNIV CATHOLIQUE LOUVAIN,B-1348 LOUVAIN,BELGIUM. MONTREAL HEART INST,MONTREAL H1T 1C8,QUEBEC,CANADA. OI Bourassa, Martial G./0000-0002-4439-8650 NR 27 TC 584 Z9 590 U1 2 U2 8 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 14 PY 1992 VL 340 IS 8829 BP 1173 EP 1178 DI 10.1016/0140-6736(92)92889-N PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JY386 UT WOS:A1992JY38600001 PM 1359258 ER PT J AU CADET, JL ZHU, SM AF CADET, JL ZHU, SM TI THE INTRASTRIATAL 6-HYDROXYDOPAMINE MODEL OF HEMIPARKINSONISM - QUANTITATIVE RECEPTOR AUTORADIOGRAPHIC EVIDENCE OF CORRELATION BETWEEN CIRCLING BEHAVIOR AND PRESYNAPTIC AS WELL AS POSTSYNAPTIC NIGROSTRIATAL MARKERS IN THE RAT SO BRAIN RESEARCH LA English DT Article DE 6-HYDROXYDOPAMINE; STRIATUM; ROTATION; QUANTITATIVE AUTORADIOGRAPHY; DOPAMINE UPTAKE SITE; DOPAMINE RECEPTOR; APOMORPHINE; AMPHETAMINE ID ROTATIONAL BEHAVIOR; SUBSTANTIA-NIGRA; DENERVATED RATS; 6-OHDA LESIONS; MESSENGER-RNA; DOPAMINE; APOMORPHINE; STRIATUM; NEURONS; BINDING AB Unilateral injections of 6-hydroxydopamine into the striatum resulted in almost immediate ipsilateral amphetamine (AMPH)- and delayed contralateral apomorphine (APO)-induced circling behavior in rats. APO-induced rotation correlated positively with that caused by AMPH. In these animals, there was an almost complete disappearance of dopamine uptake sites as well as increases in DA D2 receptors in specific subdivisions of the ipsilateral caudate-putamen (CPu). Both the rate of AMPH- and of APO-induced rotation correlated with the percentage of DA terminal loss in the total aspect and in various quadrants of the striatum. In contrast, AMPH- and APO-induced rotation correlated with the percentage increase in striatal D2 receptors only in the dorsolateral (DL) aspect of the CPu. These results indicate that both AMPH- and APO-induced rotation can be used to determine the extent of DA terminal loss in the rat basal ganglia. The positive correlation of circling behavior to only changes in DA D2 receptors observed in the DL striatal subdivision provides further evidence for the heterogeneity of the basal ganglia. This model of hemiparkinsonism in the rat which uses a distant intrastriatal approach to the destruction of nigral DA cell bodies may be a more appropriate model to study the regenerative properties of the nigrostriatal DA system. This approach could also be used to more specifically localize peptidergic receptors on midbrain dopamine cell bodies. C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032. RP CADET, JL (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,CELLULAR & MOLEC NEUROTOXICOL UNIT,POB 5180,BALTIMORE,MD 21224, USA. NR 54 TC 56 Z9 57 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 13 PY 1992 VL 595 IS 2 BP 316 EP 326 DI 10.1016/0006-8993(92)91066-N PG 11 WC Neurosciences SC Neurosciences & Neurology GA JZ047 UT WOS:A1992JZ04700020 PM 1467973 ER PT J AU KASTAN, MB ZHAN, QM ELDEIRY, WS CARRIER, F JACKS, T WALSH, WV PLUNKETT, BS VOGELSTEIN, B FORNACE, AJ AF KASTAN, MB ZHAN, QM ELDEIRY, WS CARRIER, F JACKS, T WALSH, WV PLUNKETT, BS VOGELSTEIN, B FORNACE, AJ TI A MAMMALIAN-CELL CYCLE CHECKPOINT PATHWAY UTILIZING P53 AND GADD45 IS DEFECTIVE IN ATAXIA-TELANGIECTASIA SO CELL LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; DNA DAMAGE; SACCHAROMYCES-CEREVISIAE; IONIZING-RADIATION; PROTEIN; GENE; CANCER; INDUCTION; REPLICATION; DEGRADATION AB Cell cycle checkpoints can enhance cell survival and limit mutagenic events following DNA damage. Primary murine fibroblasts became deficient in a G1 checkpoint activated by ionizing radiation (IR) when both wild-type p53 alleles were disrupted. In addition, cells from patients with the radiosensitive, cancer-prone disease ataxia-telangiectasia (AT) lacked the IR-induced increase in p53 protein levels seen in normal cells. Finally, IR induction of the human GADD45 gene, an induction that is also defective in AT cells, was dependent on wild-type p53 function. Wild-type but not mutant p53 bound strongly to a conserved element in the GADD45 gene, and a p53-containing nuclear factor, which bound this element, was detected in extracts from irradiated cells. Thus, we identified three participants (AT gene(s), p53, and GADD45) in a signal transduction pathway that controls cell cycle arrest following DNA damage; abnormalities in this pathway probably contribute to tumor development. C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. RP KASTAN, MB (reprint author), JOHNS HOPKINS ONCOL CTR,600 N WOLFE ST,BALTIMORE,MD 21287, USA. RI Carrier, France/C-3063-2008; Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [CA 09071, CA 43460]; NIEHS NIH HHS [ES 05777] NR 56 TC 3021 Z9 3050 U1 7 U2 90 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 13 PY 1992 VL 71 IS 4 BP 587 EP 597 DI 10.1016/0092-8674(92)90593-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JY676 UT WOS:A1992JY67600007 PM 1423616 ER PT J AU RIVIER, J PORTER, J HOEGER, C THEOBALD, P CRAIG, AG DYKERT, J CORRIGAN, A PERRIN, M HOOK, WA SIRAGANIAN, RP VALE, W RIVIER, C AF RIVIER, J PORTER, J HOEGER, C THEOBALD, P CRAIG, AG DYKERT, J CORRIGAN, A PERRIN, M HOOK, WA SIRAGANIAN, RP VALE, W RIVIER, C TI GONADOTROPIN-RELEASING-HORMONE ANTAGONISTS WITH N-OMEGA-TRIAZOLYLORNITHINE, N-OMEGA-LYSINE, OR N-OMEGA-P-AMINOPHENYLALANINE RESIDUES AT POSITION-5 AND POSITION-6 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; LUTEINIZING-HORMONE; CYANOGUANIDINO MOIETIES; HISTAMINE-RELEASE; GNRH ANTAGONIST; LHRH; INHIBITION; SECRETION; PEPTIDES; BINDING AB In order to be used as fertility regulators in humans, gonadotropin releasing hormone (GnRH) antagonists must be extremely potent and long acting and exhibit negligible side effects such as stimulating histamine release. To this aim, we have recently synthesized a series of analogues with the standard Ac-DNal1-DCpa2-DPal3 substitutions, where the N(omega)-amino function of ornithine, lysine, or p-aminophenylalanine (Aph) was converted to the aminotriazolyl (atz) derivatives at positions 5 and 6 with further modifications at positions 7 and 10. The analogues were tested for their ability to bind to pituitary cell membranes, to release histamine in a mast cell assay, to inhibit luteinizing hormone (LH) secretion by castrated male rats or cultured pituitary cells, and to interfere with the ovulation in intact female rats. While the subcutaneous (sc) injection of 50 mug of Azaline A {7, [AC-DNal1,DCpa2,DPal3,Lys5(atz),DLys6(atz),ILys,DAla10]GnRH} dissolved in 0.2 mL of an aqueous media significantly inhibited LH release in the castrated male rat for 24 h, the same dose of Azaline B (11), [Ac-DNal1,DCpa2,DPal3,Aph5(atz),DAph6(atz),ILys8,DAla10]GnRH, inhibited LH release for 72 h. A similar long duration of action was observed for Antide{[AC-DNal1,DCpa2,DPal3,-Lys5(Nic),DLys6(Nic),ILys8,DAla10]GnRH} but not for Nal-Glu {[AC-DNal1,DCpa2,DPal3,Arg,4-(p-methoxybenzoyl)-D-2-Abu6,DAla10]GnRH}. In the same paradigm, a 5-fold dilution of the peptide (50 mug in 1 mL) and the use of three injection sites rather than one resulted in significantly shorter duration of action for most of the peptides tested. This suggested that long duration of action might be the result of slow release from the injection site(s). In order to investigate this possibility, Nal-Glu and Azaline B were injected intravenously (iv) at three doses (10, 50, 250 mug) to castrated male rats. At all doses, both peptides significantly lowered LH levels for 8 h. By 24 h, Nal-Glu (250 mug) and Azaline B (50 and 250 mug) still measurably inhibited LH secretion. Finally, only Azaline B (250 mug) was still active at 48 h. These findings demonstrate that subtle structural modifications will yield peptides with different half-lives after iv administration. These findings led us to investigate the effects of other structural modifications on duration of action. We observed that systematic substitutions at positions 7 (NMeLeu) and 10 (Pro9-NHEt, and Gly-NH2) were found to be deleterious. Of interest was the observation that only the DAla10-NH2 substitution led to long duration of action and enzymatic stability under the conditions tested. Most analogues {excluding [AC-DNal1,DCpa2,DPal3,DCit6,DAla10]GnRH (SB-75), [AC-DNal1,DCpa2,DPal3,DHar6-(N(g),N(g')-Et2),Har8(N(g),N(g)'-Et2),DAla10]GnRH (RS-26306) and ([AC-DNal1,DCpa2,DPal3,NMeTyr5,DLys6-(Nic),ILys8,DAla10]GnRH (A-75998) which were recently reported to be long acting} were tested for binding affinity to pituitary cell membranes. On the basis of the limited data obtained in that assay, a correlation may exist between nonparallelism {with the standard [DAla6,NMeLeU7,Pro9-NHEt]GnRH} in the dose-response curve and long duration of action. In an in vitro histamine release assay and the rat antiovulatory assay (AOA), Azaline B (ED50 = 224 +/- 23 mug/mL: AOA ED100 = 1.0 mug) compared favorably against Nal-Glu (ED50 = 1.8 +/- 0.66 mug/mL: AOA ED100 = 1.5 mug), SB-75 (ED50 = 2.1 +/- 0. 3 mug/mL: AOA ED100 = 2.0 mug), RS-26306 (ED50 = 11 +/- 1.1 mug/mL: AOA ED100 greater-than-or-equal-to 2.5 mug) or A-75998 (ED50 = 22 +/- 3.2 mug/mL: AOA ED100 much greater than 1.0 mug). Azaline B is readily soluble in water/3% mannitol/5% ethanol (greater-than-or-equal-to 20 mg/mL) and is readily produced synthetically. C1 NIDR,MICROBIOL & IMMUNOL LAB,CLIN IMMUNOL SECT,BETHESDA,MD 20892. RP RIVIER, J (reprint author), SALK INST BIOL STUDIES,10010 N TORREY PINES RD,LA JOLLA,CA 92037, USA. FU NICHD NIH HHS [HD 13527, N01-HD-9-2903, N01-HD-0-2906] NR 44 TC 52 Z9 52 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 13 PY 1992 VL 35 IS 23 BP 4270 EP 4278 DI 10.1021/jm00101a003 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JY974 UT WOS:A1992JY97400003 PM 1280300 ER PT J AU DECOSTA, BR DOMINGUEZ, C HE, XS WILLIAMS, W RADESCA, L BOWEN, W AF DECOSTA, BR DOMINGUEZ, C HE, XS WILLIAMS, W RADESCA, L BOWEN, W TI SYNTHESIS AND BIOLOGICAL EVALUATION OF CONFORMATIONALLY RESTRICTED 2-(1-PYRROLIDINYL)-N-[2-(3,4-DICHLOROPHENYL)ETHYL]-N-METHYLETHYLENEDIAMI NES AS SIGMA RECEPTOR LIGANDS .1. PYRROLIDINE, PIPERIDINE, HOMOPIPERIDINE, AND TETRAHYDROISOQUINOLINE CLASSES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HIGHLY POTENT; H-3 (+)-PENTAZOCINE; OPIOID RECEPTOR; BINDING-SITES; RAT; PHENCYCLIDINE; AFFINITY; INHIBITION; AGONIST; COCAINE AB The synthesis and sigma receptor affinity of a series of conformationally restricted derivatives of 2-(1-pyrrolidinyl)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methylethylenediamine(1) is described. The pyrrolidinyl (or NN-dialkyl), ethylenediamine, N-alkyl, and phenylethyl portions of this sigma receptor pharmacophore were restricted by its incorporation into 1,2-cyclohexanediamine-, pyrrolidine-, piperidine-, homopiperidine-, and tetrahydroisoquinoline-containing ligands. The sigma receptor binding affinities of these compounds were determined using [H-3](+)-pentazocine in guinea pig brain homogenates. The synthesis of all but one class was achieved by acylation and alane reduction of the appropriate diamine precursors whose synthesis is also reported. Sigma receptor affinities ranged from 1.34 nM for 6,7-dichloro-2-[2-(l-pyrrolidinyl)ethyl]tetrahydroisoquinoline (12) to 455 nM for (1R,2R)-trans-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine [(-)-4]. In this displacement assay, (+)-pentazocine exhibited a K(i) of 3.1 nM while DTG and haloperidol showed K(i) values of 27.7 and 3.7 nM, respectively. The conformationally free parent compound 1 exhibited a K(i) value of 2.1 nM. Comparison of both the sigma receptor affinities and nitrogen atom geometry of the compounds revealed that a gauche relation of the nitrogen atoms of cis-1,2-cyclohexanediamines is not imperative for high affinity as we had previously thought. It is highly likely that nitrogen lone pair orientations and steric factors on the aliphatic portions of these ligands play a major role in the a receptor binding of this pharmacophore. RP DECOSTA, BR (reprint author), NIDDKD,MED CHEM LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 47 TC 34 Z9 34 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 13 PY 1992 VL 35 IS 23 BP 4334 EP 4343 DI 10.1021/jm00101a011 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JY974 UT WOS:A1992JY97400011 PM 1447735 ER PT J AU MOSCHEL, RC MCDOUGALL, MG DOLAN, ME STINE, L PEGG, AE AF MOSCHEL, RC MCDOUGALL, MG DOLAN, ME STINE, L PEGG, AE TI STRUCTURAL FEATURES OF SUBSTITUTED PURINE DERIVATIVES COMPATIBLE WITH DEPLETION OF HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-TUMOR-CELLS; ALKYLATING-AGENTS; SENSITIVITY AB A series of O6- and S6-substituted purine derivatives were tested for their ability to deplete the human DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) in cell-free extracts from HT29 colon tumor cells and intact HT29 cells. The order of potency was O6-(p-Y-benzyl)-guanine (Y = H, F, Cl, and CH3) > O6-benzyl-2'-deoxyguanosine > O6-(p-Y-benzyl)guanosine (Y = H, Cl, and CH3) greater-than-or-equal-to a series of 9-substituted O6-benzylguanine derivatives greater-than-or-equal-to O6-allylguanine > O6-benzylhypoxanthine > O6-methylguanine. A series of 7-substituted O6-benzylguanine derivatives, 2-amino-6-(p-Y-benzylthio)purine (Y = H, CH3),2-amino-6-[(p-nitrobenzyl)thiol-9-beta-D-ribofuranosylpurine, and 7-benzylguanine were inactive. It is concluded that for efficient AGT depletion, an allyl or benzyl group attached through exocyclic oxygen at position 6 of a 2-aminopurine derivative is required. Activity is preserved with a variety of substituent groups attached to position 9 while substitution at position 7 leads to a complete loss of activity. C1 UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,CHICAGO,IL 60637. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PHARMACOL,HERSHEY,PA 17033. RP MOSCHEL, RC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [CA-18137, N01-CO-74101, CA-47228] NR 19 TC 109 Z9 110 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 13 PY 1992 VL 35 IS 23 BP 4486 EP 4491 DI 10.1021/jm00101a028 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JY974 UT WOS:A1992JY97400028 PM 1447749 ER PT J AU CLERICI, M SHEARER, GM AF CLERICI, M SHEARER, GM TI UV-LIGHT EXPOSURE AND HIV REPLICATION SO SCIENCE LA English DT Letter RP CLERICI, M (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 2 Z9 2 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 NOV 13 PY 1992 VL 258 IS 5085 BP 1070 EP 1071 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JX852 UT WOS:A1992JX85200005 PM 1439812 ER PT J AU CANNONALBRIGHT, LA GOLDGAR, DE MEYER, LJ LEWIS, CM ANDERSON, DE FOUNTAIN, JW HEGI, ME WISEMAN, RW PETTY, EM BALE, AE OLOPADE, OI DIAZ, MO KWIATKOWSKI, DJ PIEPKORN, MW ZONE, JJ SKOLNICK, MH AF CANNONALBRIGHT, LA GOLDGAR, DE MEYER, LJ LEWIS, CM ANDERSON, DE FOUNTAIN, JW HEGI, ME WISEMAN, RW PETTY, EM BALE, AE OLOPADE, OI DIAZ, MO KWIATKOWSKI, DJ PIEPKORN, MW ZONE, JJ SKOLNICK, MH TI ASSIGNMENT OF A LOCUS FOR FAMILIAL MELANOMA, MLM, TO CHROMOSOME-9P13-P22 SO SCIENCE LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; DYSPLASTIC NEVUS SYNDROME; CYTOGENETIC ANALYSIS; SYNDROME DNS; HIGH-RISK; INHERITANCE; LINKAGE; CANCER; UPDATE AB Linkage analysis of ten Utah kindreds and one Texas kindred with multiple cases of cutaneous malignant melanoma (CMM) provided evidence that a locus for familial melanoma susceptibility is in the chromosomal region 9p13-p22. The genetic markers analyzed reside in a candidate region on chromosome 9p21, previously implicated by the presence of homozygous deletions in melanoma tumors and by the presence of a germline deletion in an individual with eight independent melanomas. Multipoint linkage analysis was performed between the familial melanoma susceptibility locus (MLM) and two short tandem repeat markers, D9S126 and the interferon-alpha (IFNA) gene, which reside in the region of somatic loss in melanoma tumors. An analysis incorporating a partially penetrant dominant melanoma susceptibility locus places MLM near IFNA and D9S126 with a maximum location score of 12.71. Therefore, the region frequently deleted in melanoma tumors on 9p21 presumably contains a locus that plays a critical role in predisposition to familial melanoma. C1 UNIV UTAH,SCH MED,DEPT MED INFORMAT,SALT LAKE CITY,UT 84112. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOLEC GENET,HOUSTON,TX 77030. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. UNIV CHICAGO,MED CTR,DEPT MED,CHICAGO,IL 60637. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. UNIV WASHINGTON,SCH MED,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,DEPT PATHOL,SEATTLE,WA 98195. RP CANNONALBRIGHT, LA (reprint author), UNIV UTAH,SCH MED,DEPT INTERNAL MED,SALT LAKE CITY,UT 84112, USA. RI Lewis, Cathryn/A-5225-2010; Hegi, Monika/O-4796-2015; OI Lewis, Cathryn/0000-0002-8249-8476; Hegi, Monika/0000-0003-0855-6495; albright, lisa/0000-0003-2602-3668 FU NCI NIH HHS [CA 42014, CA 48711]; NCRR NIH HHS [RR 00064] NR 51 TC 448 Z9 453 U1 0 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 13 PY 1992 VL 258 IS 5085 BP 1148 EP 1152 DI 10.1126/science.1439824 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JX852 UT WOS:A1992JX85200032 PM 1439824 ER PT J AU FUCHS, EJ MATZINGER, P AF FUCHS, EJ MATZINGER, P TI B-CELLS TURN OFF VIRGIN BUT NOT MEMORY T-CELLS SO SCIENCE LA English DT Article ID ANTIGEN-PRESENTING CELLS; MIXED LEUKOCYTE REACTION; DENDRITIC CELLS; LYMPHOCYTES-B; BLOOD-TRANSFUSIONS; ACTIVE ENHANCEMENT; PRIMING INVIVO; SKIN-GRAFT; TOLERANCE; INDUCTION AB There are three possible outcomes when a T cell recognizes a cell bearing a self or foreign antigen. (i) The T cell is not sufficiently signaled and is unaffected. (ii) The T cell is activated. (iii) The T cell is turned off. The differentiation state of the T cell is critical to the outcome. Although both virgin and memory T cells can be activated by antigens presented by "professional" antigen-presenting cells such as dendritic cells, they differ in their responses to B cells. Experienced T cells respond to antigen presented by B cells, whereas virgin T cells are rendered tolerant. These findings may relate to the phenomena of low- and high-zone tolerance, neonatal tolerance, and the beneficial effect of blood transfusions on allograft survival. C1 NIH,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NR 56 TC 519 Z9 529 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 13 PY 1992 VL 258 IS 5085 BP 1156 EP 1159 DI 10.1126/science.1439825 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JX852 UT WOS:A1992JX85200034 PM 1439825 ER PT J AU PONS, TP AF PONS, TP TI PERCEPTUAL CORRELATES OF MASSIVE CORTICAL REORGANIZATION - RESPONSE SO SCIENCE LA English DT Article RP PONS, TP (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 13 PY 1992 VL 258 IS 5085 BP 1160 EP 1160 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JX852 UT WOS:A1992JX85200036 ER PT J AU DAOPIN, S COHEN, GH DAVIES, D AF DAOPIN, S COHEN, GH DAVIES, D TI STRUCTURAL SIMILARITY BETWEEN TRANSFORMING GROWTH-FACTOR-BETA-2 AND NERVE GROWTH-FACTOR - RESPONSE SO SCIENCE LA English DT Article ID FOLD RP DAOPIN, S (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 9 TC 8 Z9 8 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 NOV 13 PY 1992 VL 258 IS 5085 BP 1161 EP 1162 DI 10.1126/science.258.5085.1161 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JX852 UT WOS:A1992JX85200038 PM 17789087 ER PT J AU GUSTAFSON, KR BLUNT, JW MUNRO, MHG FULLER, RW MCKEE, TC CARDELLINA, JH MCMAHON, JB CRAGG, GM BOYD, MR AF GUSTAFSON, KR BLUNT, JW MUNRO, MHG FULLER, RW MCKEE, TC CARDELLINA, JH MCMAHON, JB CRAGG, GM BOYD, MR TI HIV INHIBITORY NATURAL-PRODUCTS .8. THE GUTTIFERONES, HIV-INHIBITORY BENZOPHENONES FROM SYMPHONIA-GLOBULIFERA, GARCINIA-LIVINGSTONEI GARCINIA-OVALIFOLIA AND CLUSIA-ROSEA SO TETRAHEDRON LA English DT Article ID POLYISOPRENYLATED BENZOPHENONE; STEM BARK; ISOGARCINOL; CAMBOGINOL; XANTHONES AB Extracts from species of the tropical plant genera Symphonia, Garcinia and Clusia (Guttiferae) have yielded a series of new polyisoprenylated benzophenone derivatives named guttiferones A-E (1-5). Structural assignments were based on detailed spectral analyses. These compounds inhibit the cytopathic effects of in vitro HIV infection. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,NAT PROD BRANCH,FREDERICK,MD 21702. OI Blunt, John/0000-0003-4053-4376 NR 30 TC 205 Z9 211 U1 0 U2 8 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 NOV 13 PY 1992 VL 48 IS 46 BP 10093 EP 10102 DI 10.1016/S0040-4020(01)89039-6 PG 10 WC Chemistry, Organic SC Chemistry GA JY864 UT WOS:A1992JY86400005 ER PT J AU RON, E LUBIN, J SCHNEIDER, AB AF RON, E LUBIN, J SCHNEIDER, AB TI THYROID-CANCER INCIDENCE SO NATURE LA English DT Letter C1 UNIV ILLINOIS,HUMANA HOSP,DIV ENDOCRINOL & METAB,CHICAGO,IL 60616. UNIV ILLINOIS,MICHAEL REESE HOSP,CHICAGO,IL 60616. RP RON, E (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 6 TC 65 Z9 73 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 12 PY 1992 VL 360 IS 6400 BP 113 EP 113 DI 10.1038/360113a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JX752 UT WOS:A1992JX75200036 PM 1436087 ER PT J AU IHDE, DC AF IHDE, DC TI DRUG-THERAPY - CHEMOTHERAPY OF LUNG-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SMALL-CELL-CARCINOMA; CROSS-RESISTANT CHEMOTHERAPY; COOPERATIVE-ONCOLOGY-GROUP; ALTERNATING COMBINATION CHEMOTHERAPY; LYMPH-NODE METASTASES; RANDOMIZED TRIAL; BRONCHOGENIC-CARCINOMA; STAGE-III; INDUCTION CHEMOTHERAPY; RADIATION-THERAPY RP IHDE, DC (reprint author), NCI,OFF DIRECTOR,BLDG 31,RM 11A48,BETHESDA,MD 20892, USA. NR 106 TC 385 Z9 388 U1 1 U2 11 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 NOV 12 PY 1992 VL 327 IS 20 BP 1434 EP 1441 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA JX479 UT WOS:A1992JX47900006 PM 1328881 ER PT J AU KIM, J KAYE, FJ HENSLEE, JG SHIVELY, JE PARK, JG LAI, SL LINNOILA, RI MULSHINE, JL GAZDAR, AF AF KIM, J KAYE, FJ HENSLEE, JG SHIVELY, JE PARK, JG LAI, SL LINNOILA, RI MULSHINE, JL GAZDAR, AF TI EXPRESSION OF CARCINOEMBRYONIC ANTIGEN AND RELATED GENES IN LUNG AND GASTROINTESTINAL CANCERS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CROSS-REACTING ANTIGEN; IMMUNOGLOBULIN SUPERGENE FAMILY; NEURON-SPECIFIC ENOLASE; BILIARY GLYCOPROTEIN-I; CELL-LINES; MONOCLONAL-ANTIBODY; ADHESION MOLECULE; CEA; LOCALIZATION; IDENTIFICATION AB Carcinoembryonic antigen (CEA), a tumor marker for lung cancers of small cell (SCLC) and non-small cell (NSCLC) types, belongs in a multigene family which includes non-specific cross-reacting antigen (NCA) and biliary glycoprotein I (BGP). We used specific cDNA probes and a CEA immunoassay to determine the pattern of expression in normal and malignant lung and gastrointestinal (GI) tissues. Normal lung contained high amounts of NCA and a low concentration of CEA. All 3 genes were expressed discordantly in lung tumors and cell lines. In contrast, all three genes were expressed in most GI tumor cell lines. In both lung and colorectal cell lines expression of NCA RNA was relatively high, while BGP RNA was relatively low, and the median concentrations of CEA were greater than in corresponding non-malignant tissues. While CEA protein concentrations in lung cell lines were similar to those present in GI cell lines, the ratio of NCA:CEA RNA was significantly higher in lung cancer lines than in colorectal lines. Thus, NCA constitutes most of the "CEA-like" immunoreactivity previously described in lung cancers. There was excellent concordance between expression of CEA RNA and CEA protein, as well as between concentrations of CEA protein in cell line pellets and supernatant fluids. Of interest, significantly higher rates of CEA expression were present in lung cancers expressing neuroendocrine (NE) markers. The association between CEA expression and NE cell properties is intriguing and may prove to be of clinical interest. C1 UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75235. NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20892. USN HOSP,BETHESDA,MD 20814. CITY HOPE NATL MED CTR,BECKMAN RES INT,BECKMAN RES INST,DIV IMMUNOL,DUARTE,CA 91010. SEOUL NATL UNIV & HOSP,COLL MED,DEPT SURG,SEOUL 110,SOUTH KOREA. RI kaye, frederic/E-2437-2011; Park, Jae-Gahb/J-5494-2012 NR 30 TC 40 Z9 41 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 11 PY 1992 VL 52 IS 5 BP 718 EP 725 DI 10.1002/ijc.2910520509 PG 8 WC Oncology SC Oncology GA JX961 UT WOS:A1992JX96100008 PM 1330929 ER PT J AU ENGLANDER, EW WILSON, SH AF ENGLANDER, EW WILSON, SH TI DNA DAMAGE RESPONSE OF CLONED DNA BETA-POLYMERASE PROMOTER IS BLOCKED IN MUTANT-CELL LINES DEFICIENT IN PROTEIN KINASE-A SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CYCLIC-AMP; BINDING-PROTEIN; EXCISION REPAIR; DEOXYRIBONUCLEIC-ACID; GENE-TRANSCRIPTION; REGULATORY SUBUNIT; HUMAN-FIBROBLASTS; MESSENGER-RNA; C-FOS; RESISTANT AB DNA beta-polymerase (beta-pol), one of the recognized DNA polymerizing enzymes in vertebrates, has a role in 'very short patch' gap-filling synthesis during nucleotide excision DNA repair. In human and mouse, the enzyme is encoded by a single-copy gene located on the short arm of chromosome 8 near the centromere. In a series of studies, we have found that the cloned human beta-pol promoter is regulated by signals acting through the single ATF/CRE palindrome in the core promoter. These signals include transactivation by: adenovirus E1a/E1b proteins; activated p21ras; and in CHO cells, treatment with the DNA damaging agent MNNG. Hence, several types of stimulatory signals are mediated through the single ATF/CRE site, including DNA damage induction. To understand the mechanism of beta-pol promoter activation by MNNG in CHO cells, we asked whether induction of the cAMP/protein kinase A pathway can increase transcription of the cloned promoter in this system. Agents that increase cellular cAMP levels (8-BrcAMP; forskolin and IBMx) activated the beta-pol promoter fusion gene in transient expression experiments, and a mutation in the ATF/CRE palindrome blocked this response. Thus, the ATF/CRE site appears to be cAMP responsive in the CHO cell system. We found that the activation of the cloned beta-pol promoter by MNNG does not occur with two mutant CHO cell lines that are deficient in protein kinase A activity. Further, simultaneous treatment of wild-type CHO cells, with MNNG and to elevate cAMP, failed to result in an additive effect for activation of the beta-pol promoter. Thus, these effectors may act through a common pathway. These results suggest that the activation of the cloned beta-pol promoter in CHO cells following MNNG treatment is mediated through the cAMP/protein kinase A signal transduction pathway. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 43 TC 19 Z9 19 U1 0 U2 0 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 NOV 11 PY 1992 VL 20 IS 21 BP 5527 EP 5531 DI 10.1093/nar/20.21.5527 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ634 UT WOS:A1992JZ63400002 PM 1454516 ER PT J AU HOWARD, FB MILES, HT LIU, KL FRAZIER, J RAGHUNATHAN, G SASISEKHARAN, V AF HOWARD, FB MILES, HT LIU, KL FRAZIER, J RAGHUNATHAN, G SASISEKHARAN, V TI STRUCTURE OF D(T)N.D(A)N.D(T)N - THE DNA TRIPLE HELIX HAS B-FORM GEOMETRY WITH C2'-ENDO SUGAR PUCKER SO BIOCHEMISTRY LA English DT Article ID NUCLEIC-ACID CONFORMATIONS; HOMOPURINE HOMOPYRIMIDINE; OPTIMIZED PARAMETERS; CIRCULAR-DICHROISM; RAMAN; POLYNUCLEOTIDES; PROTEINS; BINDING; DRUG; POLY(RA).POLY(DT) AB The polynucleotide helix d(T)n.d(A)n.d(T)n is the only deoxypolynucleotide triple helix for which a structure has been published, and it is generally assumed as the structural basis for studies of DNA triplexes. The helix has been assigned to an A-form conformation with C3'-endo sugar pucker by Arnott and Selsing [1974; cf. Arnott et al. (1976)]. We show here by infrared spectroscopy in D2O solution that the helix is instead B-form and that the sugar pucker is in the C2'-endo region. Distamycin A, which binds only to B-form and not to A-form helices, binds to the triple helix without displacement of the third strand, as demonstrated by CD spectroscopy and gel electrophoresis. Molecular modeling shows that a stereochemically satisfactory structure can be built using C2'-endo sugars and a displacement of the Watson-Crick base-pair center from the helix axis of 2.5 angstrom. Helical constraints of rise per residue (h = 3.26 angstrom) and residues per turn (n = 12) were taken from fiber diffraction experiments of Arnott and Selsing (1974). The conformational torsion angles are in the standard B-form range, and there are no short contacts. In contrast, we were unable to construct a stereochemically allowed model with A-form geometry and C3'-endo sugars. Arnott et al. (1976) observed that their model had short contacts (e.g., 2.3 angstrom between the phosphate-pendent oxygen on the A strand and O2 in the Hoogsteen-paired thymine strand) which are generally known to be outside the allowed range. We conclude that the triple helix d(T)n.d(A)n.d(T)n has a conformation of the B-form with sugar pucker near C2'-endo geometry. We note that since the two T strands are antiparallel, identical conformations of the two strands will result in a dyad relating the T strands. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP HOWARD, FB (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 59 TC 87 Z9 88 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 NOV 10 PY 1992 VL 31 IS 44 BP 10671 EP 10677 DI 10.1021/bi00159a005 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JX837 UT WOS:A1992JX83700005 PM 1420182 ER PT J AU JENSEN, RA BEELER, JF HEIDARAN, MA LAROCHELLE, WJ AF JENSEN, RA BEELER, JF HEIDARAN, MA LAROCHELLE, WJ TI CHARACTERIZATION OF BACULOVIRUS-EXPRESSED HUMAN-ALPHA AND BETA-PLATELET-DERIVED GROWTH-FACTOR RECEPTORS SO BIOCHEMISTRY LA English DT Article ID HUMAN INSULIN-RECEPTOR; SIMIAN SARCOMA-VIRUS; HIGH-LEVEL EXPRESSION; PDGF RECEPTOR; TYROSINE KINASE; INSECT CELLS; NUCLEOTIDE-SEQUENCE; LIGAND-BINDING; CDNA CLONING; VECTOR AB In an effort to biochemically characterize PDGF receptors and their mechanism of activation, recombinant baculovirus vectors containing the cDNAs of the human alpha PDGF receptor or beta PDGF receptor were engineered. Characterization of recombinant PDGF receptor expression in infected Sf9 insect cells by immunoblot analysis with specific PDGF receptor peptide antisera revealed that the alpha and beta PDGF receptor gene products were translated as 160- and 165-kDa transmembrane proteins, respectively. Ligand binding analysis demonstrated saturable, high-affinity binding of either I-125-labeled PDGF AA or I-125 labeled PDGF BB to Sf9 cells expressing the recombinant alpha PDGF receptor. In contrast, recombinant beta PDGF receptor expressing Sf9 cells showed high-affinity binding only for PDGF BB. Analysis of the kinetics of PDGF receptor expression demonstrated that receptor number increased dramatically from 24- to 48-h postinfection. Early in infection, the PDGF receptors were present in low numbers, lacked tyrosine phosphorylation, and exhibited ligand-dependent tyrosine phosphorylation. However, with increasing time postinfection and increasing receptor number, the PDGF receptors became constitutively tyrosine phosphorylated in serum free culture medium. Cross-linking studies revealed that receptor activation involved ligand-independent receptor dimer formation at high receptor number. Thus, these results strongly suggest that PDGF stabilizes and increases the frequency of PDGF receptor interaction, which ultimately results in PDGF receptor activation and intracellular signaling. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 29 TC 27 Z9 27 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 NOV 10 PY 1992 VL 31 IS 44 BP 10887 EP 10892 DI 10.1021/bi00159a032 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JX837 UT WOS:A1992JX83700032 PM 1384702 ER PT J AU HERMOUET, S DEMAZANCOURT, P SPIEGEL, AM FARQUHAR, MG WILSON, BS AF HERMOUET, S DEMAZANCOURT, P SPIEGEL, AM FARQUHAR, MG WILSON, BS TI HIGH-LEVEL EXPRESSION OF TRANSFECTED G-PROTEIN ALPHA-I3 SUBUNIT IS REQUIRED FOR PLASMA-MEMBRANE TARGETING AND ADENYLYL CYCLASE INHIBITION IN NIH 3T3 FIBROBLASTS SO FEBS LETTERS LA English DT Article DE FIBROBLASTS; G-ALPHA-I3 (G-PROTEINS); ADENYLYL CYCLASE; GOLGI ID SUBCELLULAR-LOCALIZATION; SIGNAL TRANSDUCTION; PERTUSSIS TOXIN; GOLGI MEMBRANES; CYCLIC-AMP; CELLS; BINDING; IDENTIFICATION; QUANTITATION; RETICULUM AB The alpha subunits of pertussis toxin-sensitive G proteins G(i1), G(i2) and G(i3) have been shown to inhibit adenylyl cyclase in transfected cells. However, G(i3) has recently been associated with protein transport and localized to the Golgi apparatus in a number of cell lines, rather than to the plasma membrane. We studied NIH 3T3 clones stably expressing different levels of a constitutively activated mutant of the alpha subunit of G(i3) (alpha(i3)-Q204L). Transfected alpha(i3) subunits were localized to the Golgi apparatus in all NIH 3T3 clones. In clones expressing alpha(i3)-Q204L at high levels, alpha(i3) subunits were also localized to the plasma membrane. Those clones which demonstrated expression of alpha(i3) at the plasma membrane showed a 40% to 60% inhibition of forskolin-induced cAMP accumulation. Transfected NIH 3T3 clones in which plasma membrane alpha(i3) was undetectable, did not show inhibition of forskolin-induced cAMP accumulation. These data suggest that, unless high expression is achieved in transfected cells, alpha(i3) is targeted predominantly to the Golgi, not to the plasma membrane, and does not control adenylyl cyclase activity in NIH 3T3 fibroblasts. C1 UNIV CALIF SAN DIEGO,DEPT CELLULAR & MOLEC MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR MOLEC DIS,LA JOLLA,CA 92093. RP HERMOUET, S (reprint author), NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,ROOM 8C101,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA 46128]; NIDDK NIH HHS [DK 17780] NR 34 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 9 PY 1992 VL 312 IS 2-3 BP 223 EP 228 DI 10.1016/0014-5793(92)80940-I PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JY759 UT WOS:A1992JY75900026 PM 1330693 ER PT J AU ICHIKAWA, H JACOBOWITZ, DM SUGIMOTO, T AF ICHIKAWA, H JACOBOWITZ, DM SUGIMOTO, T TI CALRETININ-IMMUNOREACTIVITY IN THE OROFACIAL AND PHARYNGEAL REGIONS OF THE RAT SO NEUROSCIENCE LETTERS LA English DT Article DE CALRETININ; OROFACIAL TISSUE; PHARYNX; TRIGEMINAL GANGLION; SUPERIOR CERVICAL GANGLION; OTIC GANGLION; SUBMANDIBULAR GANGLION; NERVE ENDING ID GENE-RELATED-PEPTIDE; CALCIUM-BINDING PROTEIN; CONTAINING NERVE-FIBERS; SUBSTANCE-P; LOCALIZATION; TONGUE; ORIGIN; INNERVATION; PAPILLAE; NEURONS AB Calretinin-immunoreactivity (CR-ir) was examined in the rat oro-facial and pharyngeal tissues using an immunofluorescence method. CR-ir was distributed in the entire size range of trigeminal ganglion neurons. CR-ir was also observed in nerve fibers surrounding neuronal cell bodies in autonomic ganglia, and in nerve endings in the lip, tongue, incisal papilla, soft palate, pharynx and epiglottis. CR-immunoreactive nerve endings were all in close proximity to the epithelium, and classified into 2 types; simple (free nerve ending) and taste-bud-related types. In the salivary gland, positive nerve fibers were seen around large excretory ducts. The present study indicates that viscerosensory (probably including gustatory) nerve fibers innervating the oral and pharyngeal tissues contain CR, while somotosensory nerve fibers innervating the facial skin are devoid of CR. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP ICHIKAWA, H (reprint author), OKAYAMA UNIV,SCH DENT,DEPT ORAL ANAT 2,2-5-1 SHIKATA CHO,OKAYAMA 700,JAPAN. NR 28 TC 32 Z9 32 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 NOV 9 PY 1992 VL 146 IS 2 BP 155 EP 158 DI 10.1016/0304-3940(92)90066-G PG 4 WC Neurosciences SC Neurosciences & Neurology GA KA781 UT WOS:A1992KA78100009 PM 1491782 ER PT J AU HENEINE, W WOODS, T GREEN, D FUKUDA, K GIUSTI, R CASTILLO, L ARMIEN, B GRACIA, F KAPLAN, JE AF HENEINE, W WOODS, T GREEN, D FUKUDA, K GIUSTI, R CASTILLO, L ARMIEN, B GRACIA, F KAPLAN, JE TI DETECTION OF HTLV-II IN BREAST-MILK OF HTLV-II INFECTED MOTHERS SO LANCET LA English DT Letter ID VIRUS TYPE-I; TRANSMISSION C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. GORGAS MEM LAB,PANAMA CITY,PANAMA. RP HENEINE, W (reprint author), CTR DIS CONTROL,RETROVIRUS DIS BRANCH,ATLANTA,GA 30333, USA. NR 10 TC 24 Z9 25 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 NOV 7 PY 1992 VL 340 IS 8828 BP 1157 EP 1158 DI 10.1016/0140-6736(92)93182-M PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JX134 UT WOS:A1992JX13400024 PM 1359225 ER PT J AU KORF, HW WHITE, BH SCHAAD, NC KLEIN, DC AF KORF, HW WHITE, BH SCHAAD, NC KLEIN, DC TI RECOVERIN IN PINEAL ORGANS AND RETINAE OF VARIOUS VERTEBRATE SPECIES INCLUDING MAN SO BRAIN RESEARCH LA English DT Article DE PINEAL; RECOVERIN; DEVELOPMENT; VISION; EVOLUTION ID S-ANTIGEN; GUANYLATE-CYCLASE; RHODOPSIN KINASE; GLAND; CALCIUM; PHOTORECEPTORS; TRANSDUCERS; PROTEINS; BINDING; SYSTEMS AB Recoverin is a recently discovered 26 kDa calcium-binding protein, which activates guanylate cyclase in retinal photoreceptors when the intracellular concentration of free calcium drops upon photoexcitation. In this study we examined the distribution of recoverin in retinae and pineal organs of Xenopus laevis larvae, 1-day-old chicken, adult pigeon, albino rat, sheep and man by means of immunocytochemistry. Recoverin immunoreaction was found in all species investigated except for the chicken. In the retina, recoverin immunoreaction was restricted to photoreceptors; all other cell types were immunonegative. In the pineal organ, the recoverin immunoreaction labeled 'pinealocytes of the sensory line', i.e. classical pineal photoreceptors of Xenopus laevis larvae, modified pineal photoreceptors of pigeon, and pinealocytes of mammals. The number of recoverin immunoreactive pinealocytes varied considerably among species of mammals: very few cells were stained in the rat pineal organ, whereas in rabbit, sheep and man, numerous pinealocytes were found to be recoverin-immunoreactive. No immunocytochemical staining was observed after preabsorption of the recoverin antibody with the recombinant protein. Immunoblotting experiments showed that the immunoreaction is due to a protein of 26 kDa in both retina and pineal tissue. Thus, recoverin appears to belong to the family of proteins which are expressed in both retina and pineal organ and are highly conserved in the course of phylogeny. Recoverin may be involved in phototransduction in the directly light-sensitive pineal organs of poikilothermic vertebrates and birds. However, the functional role of recoverin in the mammalian pineal organ, which is not photosensitive, remains unknown. C1 NIH,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BLDG 36,ROOM 4A07,BETHESDA,MD 20892. UNIV FRANKFURT,CTR MORPHOL,ENVIRONM SCI & FORESTRY SECT,W-6000 FRANKFURT,GERMANY. NR 32 TC 68 Z9 71 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 6 PY 1992 VL 595 IS 1 BP 57 EP 66 DI 10.1016/0006-8993(92)91452-K PG 10 WC Neurosciences SC Neurosciences & Neurology GA JY259 UT WOS:A1992JY25900008 PM 1467959 ER PT J AU SAAVEDRA, JE DUNAMS, TM FLIPPENANDERSON, JL KEEFER, LK AF SAAVEDRA, JE DUNAMS, TM FLIPPENANDERSON, JL KEEFER, LK TI SECONDARY AMINE NITRIC-OXIDE COMPLEX-IONS, R2N[N(O)NO]- - O-FUNCTIONALIZATION CHEMISTRY SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article AB Alkylation of the R2N[N(O)NO]- anion has been studied with the aim of extending the reaction's scope, probing its stereochemistry, and exploring the reactivity of its variously functionalized products. Using the sodium salt of the R = Et ion (1) as the standard starting material, numerous novel products having the structure Et2N[N2O2]R]' (2) were isolated from its reaction with alkyl halides, sulfate esters, and oxiranes. In addition to previously described examples in which R' is a simple straight-chain alkyl or benzyl group, new compound types in which R' is hydroxylated, halide-containing, alpha-methoxylated, and olefinic were prepared. The 2-bromoethyl derivative could be dehydrohalogenated to the O-vinyl compound or further reacted with other nucleophiles such as amines, water, or a second mole of 1 to produce additional new compound types. Ethylation of 1 appeared to occur exclusively at the terminal oxygen to give Et2NN(O)=NOEt as the only isomer detected; this conclusion regarding the regiochemistry of the reaction conflicts with that found in the previous literature, but its generality was supported by X-ray crystallographic analysis of the Et2NN(O)=NOCH2CH2(NC5H5)+Br- analogue. Hydrolytic decomposition of 2 was slow, even for the O-vinyl and -methoxymethyl derivatives, as reflected in the sluggish loss of the intense chromophore these compounds characteristically show at 225-245 nm (epsilon (6.5-9) x 10(3) M-1 cm-1); half-lives at 37-degrees-C for the latter two compounds were 12 h in 0.1 M HCl and 9 h in 1 M HCl respectively. N-Nitrosodiethylamine was a frequent byproduct of both the synthesis and hydrolysis of 2. The results should aid the effort to design prodrug derivatives of 1, a compound type which has recently been shown to exhibit useful pharmacological effects. C1 USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. RP SAAVEDRA, JE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 20 TC 83 Z9 84 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 6 PY 1992 VL 57 IS 23 BP 6134 EP 6138 DI 10.1021/jo00049a017 PG 5 WC Chemistry, Organic SC Chemistry GA JX822 UT WOS:A1992JX82200017 ER PT J AU LUNN, G AF LUNN, G TI PREPARATION OF PIPERIDINYLPYRIDINES VIA SELECTIVE REDUCTION OF BIPYRIDINES WITH NICKEL ALUMINUM-ALLOY SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID C-13 NMR; ALPHA-AMINONITRILES; TOBACCO ALKALOIDS; 1,10-PHENANTHROLINES; 2,2'-BIPYRIDYLS; PIPERIDINES; PYRIDINES; FACILE AB Bipyridines were reduced to piperidinylpyridines in modest yield using nickel-aluminum alloy in potassium hydroxide solution. The reduction was selective, and 3-substituted rings were reduced in preference to 4-substitution in preference to 2-substitution. Thus 2,3-bipyridine gave only 2-(3'-piperidinyl)pyridine, 2,4-bipyridine gave only 2-(4'-piperidinyl)pyridine, and 3,4-bipyridine gave only 4-(3'-piperidinyl)pyridine. The symmetrial 2,2'- and 4,4'-bipyridines also gave the corresponding piperidinylpyridines, but the reduction of 3,3'-bipyridine was too sluggish to be practical. The products were identified using C-13 NMR spectrospy, and the C-13 NMR spectra of the starting bipyridines were also recorded. RP LUNN, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,ENVIRONM CONTROL & RES PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 44 TC 16 Z9 17 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 6 PY 1992 VL 57 IS 23 BP 6317 EP 6320 DI 10.1021/jo00049a046 PG 4 WC Chemistry, Organic SC Chemistry GA JX822 UT WOS:A1992JX82200046 ER PT J AU WETTERAU, JR AGGERBECK, LP BOUMA, ME EISENBERG, C MUNCK, A HERMIER, M SCHMITZ, J GAY, G RADER, DJ GREGG, RE AF WETTERAU, JR AGGERBECK, LP BOUMA, ME EISENBERG, C MUNCK, A HERMIER, M SCHMITZ, J GAY, G RADER, DJ GREGG, RE TI ABSENCE OF MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN IN INDIVIDUALS WITH ABETALIPOPROTEINEMIA SO SCIENCE LA English DT Article ID APOLIPOPROTEIN-B GENE; CHOLESTERYL ESTER; DISULFIDE ISOMERASE; HYPOBETALIPOPROTEINEMIA; TRIACYLGLYCEROL; COMPLEX; DISEASE; CELLS AB Abetalipoproteinemia is a human genetic disease that is characterized by a defect in the assembly or secretion of plasma very low density lipoproteins and chylomicrons. The microsomal triglyceride transfer protein (MTP), which is located in the lumen of microsomes isolated from the liver and intestine, has been proposed to function in lipoprotein assembly. MTP activity and the 88-kilodalton component of MTP were present in intestinal biopsy samples from eight control individuals but were absent in four abetalipoproteinemic subjects. This finding suggests that a defect in MTP is the basis for abetalipoproteinemia and that MTP is indeed required for lipoprotein assembly. C1 CNRS,CTR GENET MOLEC,F-91198 GIF SUR YVETTE,FRANCE. UNIV PARIS 07,INSERM,U327,F-75018 PARIS,FRANCE. HOP ST NICOLAS,SERV MED INTERNE,F-55107 VERDUN,FRANCE. HOP EDOUARD HERRIOT,MED INFANTILE CLIN B,F-69437 LYON,FRANCE. HOP ROBERT DEBRE,SERV GASTROENTEROL NUTR PEDIAT,F-75019 PARIS,FRANCE. HOP NECKER ENFANTS MALAD,DEPT PEDIAT,F-75730 PARIS 15,FRANCE. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. RP WETTERAU, JR (reprint author), BRISTOL MYERS SQUIBB,DEPT METABOL DIS,PRINCETON,NJ 08543, USA. FU NHLBI NIH HHS [HL18577] NR 19 TC 525 Z9 535 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 6 PY 1992 VL 258 IS 5084 BP 999 EP 1001 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW796 UT WOS:A1992JW79600036 PM 1439810 ER PT J AU BONOW, RO DILSIZIAN, V AF BONOW, RO DILSIZIAN, V TI ASSESSING VIABLE MYOCARDIUM WITH TL-201 SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT SYMP ON CARDIAC IMAGING AND PATIENT MANAGEMENT, AT THE 1991 ANNUAL MEETING OF THE AMERICAN HEART ASSOC CY NOV 09, 1991 CL ANAHEIM, CA SP AMER HEART ASSOC, MALLINCKRODT MED ID POSITRON EMISSION TOMOGRAPHY; LEFT-VENTRICULAR DYSFUNCTION; WALL-MOTION ABNORMALITIES; STRESS-REDISTRIBUTION; TL-201 REINJECTION; METABOLIC-ACTIVITY; LATE REVERSIBILITY; CORONARY REVASCULARIZATION; HIBERNATING MYOCARDIUM; BYPASS SURGERY AB Patients with chronic coronary artery diseaese and potentially reversible left ventricular dysfunction can often be successfully identified by one or mom clinical indicators af myocardial viability, including regional wall motion, systolic wall thickening, regional myocardial perfusion as determined by perfusion tracers, and redistribution af thallium-201. In some patients, however, viable but "hibernating" myocardium will exist even when none of the above are evident. Myocardial viability in this situation can be detected with a high degree af accuracy by the demonstration of preserved metabolic activity by positron emission tomography (PET) scanning, Additionally, modifications af the standard exercise-redistribution thallium protocol may also produce accurate results. These modifications include late thallium-201 redistribution imaging, performed 8-72 hours following initial thallium injection, and thallium reinjection at rest after early (3-4 hours) or late (8=72 hours) redistribution imaging. These methods can identify viable myocardium in many thallium defects that appear to be irreversible on a standard 3-4 hour redistribution image. In addition, serial imaging after administration of thallium-201 at rest may also provide valuable insights into myocardial viability. These imaging modalities have important practical applications in the evaluation and management af patients with coronary artery disease and left ventricular dysfunction. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RP BONOW, RO (reprint author), NORTHWESTERN UNIV,SCH MED,DIV CARDIOL,250 E SUPER ST,524,CHICAGO,IL 60611, USA. NR 54 TC 26 Z9 26 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 NOV 5 PY 1992 VL 70 IS 14 BP E10 EP E17 DI 10.1016/0002-9149(92)90033-U PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JY039 UT WOS:A1992JY03900003 PM 1442566 ER PT J AU ABDULLAH, M HUGHES, PJ CRAXTON, A GIGG, R DESAI, T MARECEK, JF PRESTWICH, GD SHEARS, SB AF ABDULLAH, M HUGHES, PJ CRAXTON, A GIGG, R DESAI, T MARECEK, JF PRESTWICH, GD SHEARS, SB TI PURIFICATION AND CHARACTERIZATION OF INOSITOL-1,3,4-TRISPHOSPHATE 5 6-KINASE FROM RAT-LIVER USING AN INOSITOL HEXAKISPHOSPHATE AFFINITY COLUMN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADRENAL GLOMERULOSA CELLS; MYOINOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE; 1,3,4-TRISPHOSPHATE PHOSPHORYLATION; AVIAN ERYTHROCYTES; ACINAR-CELLS; 1,3,4,6-TETRAKISPHOSPHATE; TETRAKISPHOSPHATE; 1,3,4,5-TETRAKISPHOSPHATE; 1,4,5-TRISPHOSPHATE; PHOSPHATES AB The metabolism of inositol 1,3,4-trisphosphate is a pivotal branch point of inositol phosphate turnover; its dephosphorylation replenishes cellular inositol pools, its phosphorylation at the 6-position supports the synthesis of inositol pentakisphosphate, and its phosphorylation at the 5-position produces inositol 1,3,4,5-tetrakisphosphate Shears, S. B. (1989) J. Biol. Chem. 264, 19879-19886). In order to increase understanding of the control of inositol-1,3,4-trisphosphate kinase activity, the enzyme was highly purified from rat liver by precipitation with polyethylene glycol, MonoQ ion-exchange chromatography, heparin-agarose affinity chromatography, and a novel affinity chromatography procedure that utilized Affi-Gel resin to which InSP6 was coupled (Marecek, J. F., and Prestwich, G. D. (1991) Tetrahedron Lett. 32, 1863-1866). The final purification was about 26,000-fold, with a 6% yield. This final preparation performed both 5- and 6-kinase activities in the ratio of approximately 1:5. The affinity of the enzyme for inositol 1,3,4-trisphosphate was 0.04 muM, the highest yet determined for an inositol phosphate kinase. Both inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4,6-tetrakisphosphate were competitive inhibitors of the kinase (K(i) values of 2-4 muM). The enzyme was determined to have a molecular mass of 36 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Kinase activity was unaffected by Ca2+/calmodulin, protein kinase A, or protein kinase C. C1 NIEHS, INOSITOL LIPID SECT, CELLULAR & MOLEC PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. NATL INST MED RES, LONDON NW7 1AA, ENGLAND. SUNY STONY BROOK, DEPT CHEM, STONY BROOK, NY 11794 USA. FU NINDS NIH HHS [NS 29632] NR 34 TC 33 Z9 34 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 5 PY 1992 VL 267 IS 31 BP 22340 EP 22345 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW719 UT WOS:A1992JW71900056 PM 1331051 ER PT J AU GUERINI, D MONTELL, C KLEE, CB AF GUERINI, D MONTELL, C KLEE, CB TI MOLECULAR-CLONING AND CHARACTERIZATION OF THE GENES ENCODING THE 2 SUBUNITS OF DROSOPHILA-MELANOGASTER CALCINEURIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN PHOSPHATASE; SERINE-THREONINE PHOSPHATASES; CATALYTIC SUBUNIT; PHOSPHOPROTEIN PHOSPHATASE; SACCHAROMYCES-CEREVISIAE; CELLULAR-REGULATION; OKADAIC ACID; CDNA CLONING; KINASE-II; CALMODULIN AB Genomic clones containing the full coding sequences of the two subunits of the Ca2+/calmodulin-stimulated protein phosphatase, calcineurin, were isolated from a Drosophila melanogaster genomic library using highly conserved human cDNA probes. Three clones encoded a 19.3-kDa protein whose sequence is 88% identical to that of human calcineurin B, the Ca2+-binding regulatory subunit of calcineurin. The coding sequences of the Drosophila and human calcineurin B genes are 69% identical. Drosophila calcineurin B is the product of a single intron-less gene located at position 4F on the X chromosome. Drosophila genomic clones encoding a highly conserved region of calcineurin A, the catalytic subunit of calcineurin, were used to locate the calcineurin A gene at position 21 EF on the second chromosome of Drosophila and to isolate calcineurin A cDNA clones from a Drosophila embryonic cDNA library. The structure of the calcineurin A gene was determined by comparison of the genomic and cDNA sequences. Twelve exons, spread over a total of 6.6 kilobases, were found to encode a 64.6-kDa protein 73% identical to either human calcineurin Aalpha or beta. At the nucleotide level Drosophila calcineurin A cDNA is 67 and 65% identical to human calcineurin Aalpha and beta cDNAs, respectively. Major differences between human and Drosophila calcineurins A are restricted to the amino and carboxyl termini, including two stretches of repetitive sequences in the carboxyl-terminal third of the Drosophila molecule. Motifs characteristic of the putative catalytic centers of protein phosphatase-1 and -2A and calcineurin are almost perfectly conserved. The calmodulin-binding and auto-inhibitory domains, characteristic of all mammalian calcineurins A, are also conserved. A remarkable feature of the calcineurin A gene is the location of the intron/exon junctions at the boundaries of the functional domains and the apparent conservation of the intron/exon junctions from Drosophila to man. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM & NEUROSCI,BALTIMORE,MD 21205. OI Montell, Craig/0000-0001-5637-1482 FU NEI NIH HHS [EY08117] NR 50 TC 48 Z9 50 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 NOV 5 PY 1992 VL 267 IS 31 BP 22542 EP 22549 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW719 UT WOS:A1992JW71900086 PM 1331060 ER PT J AU POZSGAY, V AF POZSGAY, V TI A SIMPLE METHOD FOR AVOIDING ALKYLTHIO GROUP MIGRATION DURING THE SYNTHESIS OF THIOGLYCOSIDE 2,3-ORTHOESTERS - AN IMPROVED SYNTHESIS OF PARTIALLY ACYLATED 1-THIO-ALPHA-L-RHAMNOPYRANOSIDES SO CARBOHYDRATE RESEARCH LA English DT Note ID ARTIFICIAL CARBOHYDRATE ANTIGENS; COMMON POLYSACCHARIDE ANTIGEN; L-FUCOPYRANOSYL GROUPS; REPEATING-UNIT; CAPSULAR POLYSACCHARIDE; COMPLEX TYPE; OLIGOSACCHARIDES; GLYCOPROTEINS; SACCHARIDE; MOIETY C1 NIDDKD,MEDICINAL CHEM LAB,BETHESDA,MD 20892. RP POZSGAY, V (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BLDG 8-B1A-25,BETHESDA,MD 20892, USA. NR 18 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 4 PY 1992 VL 235 BP 295 EP 302 DI 10.1016/0008-6215(92)80098-L PG 8 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA KA067 UT WOS:A1992KA06700026 PM 1473109 ER PT J AU WATTERS, JK NEEDLE, R BROWN, BS WEATHERBY, N BOOTH, R WILLIAMS, M AF WATTERS, JK NEEDLE, R BROWN, BS WEATHERBY, N BOOTH, R WILLIAMS, M TI THE SELF-REPORTING OF COCAINE USE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIDA,ROCKVILLE,MD. UNIV MIAMI,SCH MED,MIAMI,FL 33152. UNIV COLORADO,DENVER,CO 80202. RP WATTERS, JK (reprint author), UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA 94143, USA. NR 3 TC 25 Z9 25 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 4 PY 1992 VL 268 IS 17 BP 2374 EP 2375 DI 10.1001/jama.268.17.2374 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JV694 UT WOS:A1992JV69400012 PM 1404789 ER PT J AU ROSENBERG, SA AF ROSENBERG, SA TI GENE-THERAPY FOR CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; CELLS; IMMUNOTHERAPY; INVIVO; INTERLEUKIN-2; EXPRESSION; HUMANS; POTENT RP ROSENBERG, SA (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 24 TC 98 Z9 101 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 NOV 4 PY 1992 VL 268 IS 17 BP 2416 EP 2419 DI 10.1001/jama.268.17.2416 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA JV694 UT WOS:A1992JV69400029 PM 1404800 ER PT J AU SMITH, MT WIEMELS, J ROTHMAN, N LINET, MS AF SMITH, MT WIEMELS, J ROTHMAN, N LINET, MS TI CHEMICAL-EXPOSURE, RAS ONCOGENE ACTIVATION, AND ACUTE MYELOID-LEUKEMIA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ACUTE NONLYMPHOCYTIC LEUKEMIA; GENE-MUTATIONS; OCCUPATION C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP SMITH, MT (reprint author), UNIV CALIF BERKELEY,SCH PUBL HLTH,CTR OCCUPAT & ENVIRONM HLTH,322 WARREN HALL,BERKELEY,CA 94720, USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 4 PY 1992 VL 84 IS 21 BP 1614 EP 1615 DI 10.1093/jnci/84.21.1614 PG 2 WC Oncology SC Oncology GA JW439 UT WOS:A1992JW43900001 PM 1433339 ER PT J AU TAYLOR, JA SANDLER, DP BLOOMFIELD, CD SHORE, DL BALL, ED NEUBAUER, A MCINTYRE, OR LIU, E AF TAYLOR, JA SANDLER, DP BLOOMFIELD, CD SHORE, DL BALL, ED NEUBAUER, A MCINTYRE, OR LIU, E TI RAS ONCOGENE ACTIVATION AND OCCUPATIONAL EXPOSURES IN ACUTE MYELOID-LEUKEMIA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GENE-MUTATIONS; CLINICAL-SIGNIFICANCE; MYELOGENOUS LEUKEMIA; PROTO-ONCOGENE; HUMAN-LUNG; ADENOCARCINOMA; PROTOONCOGENES; NEOPLASIA; TUMORS AB Background: Epidemiologic studies of acute myeloid leukemias (AMLs) show small increases in risk of disease associated with certain occupations and chemical exposures. Purpose: This study was designed to determine whether the presence of mutationally activated ras oncogenes in AML are associated with occupational and chemical exposures. Methods: We interviewed 62 patients with newly diagnosed AML (or their next-of-kin), all of whom were enrolled in a national multicenter clinical trial, and 630 healthy control subjects. DNA extracted from patients' pretreatment bone marrow samples was amplified by using the polymerase chain reaction and probed with allele-specific oligonucleotides for activating point mutations at the 12th, 13th, and 61st codons of three protooncogenes: H-ras (also known as HRAS), K-ras (also known as KRAS2), and N-ras (also known as NRAS). Results: Patients with ras mutation-positive AML had a higher frequency (six of 10 patients) of working 5 or more years in an a priori high-risk occupation than did patients with ras mutation-negative AML (eight of 52; odds ratio [OR] = 6.8; 95% confidence interval [CI] = 1.3-36). Patients with ras mutation-positive AML were more likely than patients with ras mutation-negative AML to have breathed chemical vapor on the job (OR = 9.1; 95% CI = 1.3-64) or to have had skin contact with chemicals OR = 6.9; 95% CI = 1.3-37). When ras-positive patients were compared with healthy control subjects, the ORs for occupation and occupational exposures remained elevated, while patients with ras mutation-negative AML showed no increased risk when compared with control subjects. Conclusion: Activation of ras proto-oncogenes may identify an etiologic subgroup of AML caused by occupation and chemical exposure. Implication: Disease etiology may be better understood if epidemiologic measures of exposure are integrated with molecular assays of the genetic defects responsible for cancer initiation and promotion. C1 ROSWELL PK CANC INST,DEPT MED,BUFFALO,NY. WESTAT CORP,DURHAM,NC. UNIV PITTSBURGH,MED CTR,HEMATOL BONE MARROW TRANSPLANT SECT,PITTSBURGH,PA 15260. UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC 27514. DARTMOUTH COLL,HITCHCOCK MED CTR,CANC & LEUKEMIA GRP B,HANOVER,NH 03756. RP TAYLOR, JA (reprint author), NIEHS,EPIDEMIOL BRANCH,ENVIRONM & MOLEC EPIDEMIOL SECT,MAIL DROP A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Liu, Edison/C-4141-2008; OI taylor, jack/0000-0001-5303-6398; Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [CA-31946, CA-37027, CA-49240] NR 30 TC 69 Z9 69 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 4 PY 1992 VL 84 IS 21 BP 1626 EP 1632 DI 10.1093/jnci/84.21.1626 PG 7 WC Oncology SC Oncology GA JW439 UT WOS:A1992JW43900009 PM 1433344 ER PT J AU KIBBEY, MC GRANT, DS KLEINMAN, HK AF KIBBEY, MC GRANT, DS KLEINMAN, HK TI ROLE OF THE SIKVAV SITE OF LAMININ IN PROMOTION OF ANGIOGENESIS AND TUMOR-GROWTH - AN INVIVO MATRIGEL MODEL SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; AMINO-ACID-SEQUENCE; BASEMENT-MEMBRANE; A-CHAIN; EXTRACELLULAR-MATRIX; SYNTHETIC PEPTIDE; BINDING PROTEIN; IDENTIFICATION; INVITRO AB Background: Angiogenesis (vascularization) has a critical role in tumor growth and metastasis, and peptides containing the SIKVAV amino acid sequence (Ser-Ile-Lys-Val-Ala-Val) have been shown to stimulate many angiogenic activities in vitro. The use of model systems to identify agents that stimulate or inhibit angiogenesis may lead to the development of new antitumor strategies. Purpose: Our purpose was to use an in vivo murine model system to study the angiogenic activity of a synthetic peptide derived from the laminin A protein chain and containing the SIKVAV amino acid sequence. We also examined the ability of the peptide to enhance tumor growth in vivo. Methods: The SIKVAV-containing peptide was mixed with Matrigel, a reconstituted basement membrane extract used to assay stimulation of angiogenesis. The mixture was subcutaneously injected into C57BL/6 mice. At various times after injection, the Matrigel plug was excised, and angiogenic activity was assessed by histologic examination and immunohistochemical staining with an antibody to the von Willebrand factor (vWF), an endothelium-specific antigen. In other experiments, the mixture of peptide and Matrigel was co-injected with B16F10 murine melanoma cells into C57BL/6 mice, and the resultant tumors were assessed for size and vascularization. Results: When co-injected with Matrigel at doses as low as 10 mug, the SIKVAV-containing peptide stimulated angiogenesis fourfold greater than that seen in controls, and maximum angiogenic activity was observed 2 weeks after injection. This peptide was angiogenic in a dose-dependent manner up to a 100-mug dose. When co-injected with Matrigel and B16F10 melanoma cells, the peptide enhanced tumor growth by approximately 2.5-fold, and tumor vascularization was significantly increased (P = .027) over that observed after injection with melanoma cells and Matrigel alone. Conclusions: These data demonstrate that the laminin-derived SIKVAV-containing peptide is angiogenic in a new in vivo model system and can enhance tumor vascularization and growth. RP KIBBEY, MC (reprint author), NIDR,DEV BIOL LAB,BLDG 30,RM 402,BETHESDA,MD 20892, USA. NR 32 TC 144 Z9 149 U1 0 U2 6 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 4 PY 1992 VL 84 IS 21 BP 1633 EP 1638 DI 10.1093/jnci/84.21.1633 PG 6 WC Oncology SC Oncology GA JW439 UT WOS:A1992JW43900010 PM 1279183 ER PT J AU HSIA, CC KLEINER, DE AXIOTIS, CA DIBISCEGLIE, A NOMURA, AMY STEMMERMANN, GN TABOR, E AF HSIA, CC KLEINER, DE AXIOTIS, CA DIBISCEGLIE, A NOMURA, AMY STEMMERMANN, GN TABOR, E TI MUTATIONS OF P53 GENE IN HEPATOCELLULAR-CARCINOMA - ROLES OF HEPATITIS-B VIRUS AND AFLATOXIN CONTAMINATION IN THE DIET SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID EXPRESSION; ONCOGENE AB Background: Mutations of the p53 tumor suppressor gene have been reported in 50% of patients with hepatocellular carcinoma (HCC) from China and South Africa. These reports suggested an association of p53 mutations with high levels of aflatoxin in the diet. Most studies of p53 and HCC, however, have not fully evaluated the possible role of the hepatitis B virus (HBV). Aflatoxin is a substance produced by food mold that is known to cause HCC in experimental animals. Purpose: The purpose of this study was to evaluate the relationship of p53 gene mutation to high or low levels of aflatoxin in the diet and to HBV infection. Methods: p53 protein and hepatitis B surface antigen (HBsAg) were evaluated by immunohistochemistry using the avidin-biotin-peroxidase system in paraffin-embedded specimens of HCC and of adjacent nontumorous liver tissue from 43 patients. Tissue specimens from three normal human livers were also evaluated. HCCs and adjacent nontumorous liver tissues were obtained from 23 patients from Qidong, China, where aflatoxin levels in the diet are high, and from 20 patients from two regions in the United States (patients from the National Institutes of Health, Bethesda, Md., and Kuakini Medical Center, Honolulu, Hawaii), where aflatoxin levels in the diet are low. Results: Mutant p53 protein was detected in the nuclei of HCCs from 14 (61%) of 23 patients from China and from three (30%) of 10 patients and six (60%) of 10 patients, respectively, from the two regions of the United States. A statistically significant association between detection of mutant p53 protein in HCC cells and the detection of HBsAg in hepatocytes of the adjacent nontumorous liver tissue was observed in patients from China and the United States considered together. Conclusion: Mutations of the tumor suppressor gene p53 in hepatocellular carcinomas are not limited to patients from geographic regions where the ingestion of aflatoxin is high. In many patients, these mutations may be associated with HBV infection. Implications: The possible interaction of chronic HBV infection and p53 gene mutation, suggested by these data, indicates a mechanism by which HBV infection beginning early in life could contribute to the subsequent development of HCC. C1 NCI,DIV CANC ETIOL,BIOL CARCINOGENESIS PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG,PATHOL LAB,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,HEPATITIS STUDIES SECT,BETHESDA,MD. UNION UNIV,ALBANY,NY 12208. KUAKINI MED CTR,HONOLULU,HI. OI Kleiner, David/0000-0003-3442-4453 NR 15 TC 53 Z9 57 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 4 PY 1992 VL 84 IS 21 BP 1638 EP 1641 DI 10.1093/jnci/84.21.1638 PG 4 WC Oncology SC Oncology GA JW439 UT WOS:A1992JW43900011 PM 1279184 ER PT J AU JOHNSON, ES PARSONS, W WEINBERG, CR SHORE, DL MATHEWS, J PATTERSON, DG NEEDHAM, LL AF JOHNSON, ES PARSONS, W WEINBERG, CR SHORE, DL MATHEWS, J PATTERSON, DG NEEDHAM, LL TI CURRENT SERUM LEVELS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN PHENOXY ACID HERBICIDE APPLICATORS AND CHARACTERIZATION OF HISTORICAL LEVELS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DIOXINS AB Background: Workers who sprayed phenoxy acid herbicides, especially those who sprayed before 1975, may have been exposed to significant amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent animal carcinogen present in herbicide preparations as a contaminant. Purpose: The aims of this study were (a) to determine serum levels of TCDD in a representative sample of workers occupationally exposed to the agent during the spraying of phenoxy acid herbicides; (b) to compare serum levels in workers exposed before 1965, when concentrations in herbicide products were unregulated and high, with levels in workers exposed after 1974, when concentrations were lower as a result of government regulations worldwide; and (c) to examine the correlation, if any, between serum levels and duration of employment in spraying. Methods: Thirty-seven subjects were randomly selected from a group of 654 men who had sprayed the herbicides 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid (2,4-D) in Australia for at least 12 months. The workers were classified as follows: eight who sprayed only before 1965, nine who sprayed only during the period after 1964 and before 1975, and 20 who sprayed during the period after 1974 and before 1991. Serum from the workers was analyzed for TCDD by high-resolution gas chromatography and high-resolution mass spectrometry at a detection limit of 0.6 parts per trillion (ppt) on a lipid-weight basis. In addition, rates of exposure to TCDD were estimated, as were TCDD serum concentrations at termination of employment and intensity of herbicide use. Results: Only one worker, with a serum TCDD level of 34 ppt, had a serum level higher than the maximum level of 26 ppt reported for the general population. Assuming a half-life of 7.1 years, we estimated the mean exposure rates to be 2.7, 2.3, and 0.06 ppt/mo for the three epochs, respectively. We found the highest serum level of TCDD at the time of cessation of employment to be 329 ppt. Calendar period and intensity of use of 2,4,5-T and 2,4-D were statistically significant determinants of rate of exposure to TCDD, but 2,4-D was associated with exposure rate only for the pre-1975 periods. Estimated rates prior to 1965 were more than an order of magnitude higher than those after 1974. Conclusion: The highest estimated exposure rate was 20.7 ppt/mo, which suggests that some sprayers may have been exposed to levels comparable with those that produce cancer in laboratory animals. C1 WESTAT CORP,RES TRIANGLE PK,NC. MENZIES SCH HLTH RES,DARWIN,NT,AUSTRALIA. CTR DIS CONTROL,NATL CTR ENVIRONM HLTH & INJURY CONTROL,DIV ENVIRONM HLTH LAB SCI,ATLANTA,GA 30333. RP JOHNSON, ES (reprint author), NIEHS,DIV BIOMETRY & RISK ASSESSMENT,EPIDEMIOL BRANCH,MD A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Needham, Larry/E-4930-2011; OI Mathews, John/0000-0001-9029-7140 NR 16 TC 19 Z9 19 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 4 PY 1992 VL 84 IS 21 BP 1648 EP 1653 DI 10.1093/jnci/84.21.1648 PG 6 WC Oncology SC Oncology GA JW439 UT WOS:A1992JW43900013 PM 1433346 ER PT J AU ACHARI, A HALE, SP HOWARD, AJ CLORE, GM GRONENBORN, AM HARDMAN, KD WHITLOW, M AF ACHARI, A HALE, SP HOWARD, AJ CLORE, GM GRONENBORN, AM HARDMAN, KD WHITLOW, M TI 1.67-ANGSTROM X-RAY STRUCTURE OF THE B2 IMMUNOGLOBULIN-BINDING DOMAIN OF STREPTOCOCCAL PROTEIN-G AND COMPARISON TO THE NMR STRUCTURE OF THE B1 DOMAIN SO BIOCHEMISTRY LA English DT Article ID LEAST-SQUARES REFINEMENT; CRYSTALLOGRAPHIC REFINEMENT; METHIONINE AMINOPEPTIDASE; MACROMOLECULAR STRUCTURES; 2.8-A RESOLUTION; CRYSTALLIZATION; SIMILARITY; UBIQUITIN AB The structure of the B2 immunoglobulin-binding domain of streptococcal protein G has been determined at 1.67-angstrom resolution using a combination of single isomorphous replacement (SIR) phasing and manual fitting of the coordinates of the NMR structure of B1 domain of streptococcal protein G [Gronenborn, A. M., et al. (1991) Science 253, 657-661]. The final R value was 0.191 for data between 8.0 and 1.67 angstrom. The structure described here has 13 residues preceding the 57-residue Ig-binding domain and 13 additional residues following it, for a total of 83 residues. The 57-residue binding domain is well-determined in the structure, having an average B factor of 18.0. Only residues 8-77 could be located in the electron density maps, with the ends of the structure fading into disorder. Like the B1 domain, the B2 domain consists of four beta-strands and a single helix lying diagonally across the beta-sheet, with a -1, +3x, -1 topology. This small structure is extensively hydrogen-bonded and has a relatively large hydrophobic core. These structural observations may account for the exceptional stability of protein G. A comparison of the B2 domain X-ray structure and the B1 domain NMR structure showed minor differences in the turn between strands and two and a slight displacement of the helix relative to the sheet. Hydrogen bonds between crystallographically related molecules account for most of these differences. C1 ENZON INC,DEPT PROT ENGN,16020 IND DR,GAITHERSBURG,MD 20877. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 33 TC 91 Z9 92 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 3 PY 1992 VL 31 IS 43 BP 10449 EP 10457 DI 10.1021/bi00158a006 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW440 UT WOS:A1992JW44000006 PM 1420164 ER PT J AU CHRAPUSTA, SJ KAROUM, F EGAN, MF WYATT, RJ AF CHRAPUSTA, SJ KAROUM, F EGAN, MF WYATT, RJ TI GAMMA-BUTYROLACTONE-SENSITIVE AND GAMMA-BUTYROLACTONE-INSENSITIVE DOPAMINE RELEASE, AND THEIR RELATIONSHIP TO DOPAMINE METABOLISM IN 3 RAT-BRAIN REGIONS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE DOPAMINE RELEASE; 3-METHOXYTYRAMINE; STRIATUM; NUCLEUS ACCUMBENS; FRONTAL CORTEX; (RAT) ID CENTRALLY ACTING DRUGS; SUBSTANTIA-NIGRA; TERMINAL AUTORECEPTORS; STRIATAL DOPAMINE; INVIVO RELEASE; IMPULSE FLOW; NEURONS; 3-METHOXYTYRAMINE; HYDROXYBUTYRATE; HALOPERIDOL AB Some data suggest dopamine (DA) release from neuronal terminals is partially independent of impulse flow. We examined the changes in tissue DA and its major metabolite levels 30 and 90 min after treatment with y-butyrolactone (750 mg/kg). Accumulation of 3-methoxytyramine within 10 min of pargyline injection (75 mg/kg) was used as an index of DA release. Thirty minutes after gamma-butyrolactone injection, DA content was increased maximally in the frontal cortex, nucleus accumbens and striatum (by 91%, 80% and 73%, respectively). 3-Methoxytyramine rates of accumulation were reduced by 77%, 77%, and 92%, respectively. Ninety minutes after the treatment, DA levels remained high in all three areas, while DA release was persistently low in the striatum and nucleus accumbens, but had returned to baseline in the frontal cortex. Changes in 3,4-dihydroxyphenylacetic acid and homovanillic acid levels were not synchronized with changes in DA release in the striatum and nucleus accumbens, and were absent in the frontal cortex. The data suggest that an impulse flow-independent mechanism contributes to approximately one tenth and one fourth of the basal DA release in the terminals of DA neurons originating in the substantia nigra and ventral tegmental area, respectively. The acidic DA metabolite levels become at best poorly associated with DA release during blockade of the DA neuronal firing, probably because of the increased in situ metabolism of newly synthesized DA. RP CHRAPUSTA, SJ (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,BLDG WAW,WASHINGTON,DC 20032, USA. NR 35 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 3 PY 1992 VL 222 IS 1 BP 129 EP 135 DI 10.1016/0014-2999(92)90472-G PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JY363 UT WOS:A1992JY36300019 PM 1468488 ER PT J AU MANJI, HK CHEN, G BITRAN, JA GUSOVSKY, F POTTER, WZ AF MANJI, HK CHEN, G BITRAN, JA GUSOVSKY, F POTTER, WZ TI IDAZOXAN DOWN-REGULATES BETA-ADRENOCEPTORS ON C6 GLIOMA-CELLS INVITRO SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE IDAZOXAN; ANTIDEPRESSANTS; BETA-ADRENOCEPTORS; ADENYLYL CYCLASE; C6 GLIOMA CELLS; PROTEIN KINASE-C ID ADRENERGIC-RECEPTOR BINDING; COUPLED ADENYLATE-CYCLASE; HIGH-AFFINITY; TRICYCLIC ANTIDEPRESSANT; CEREBRAL-CORTEX; G-PROTEINS; DESIPRAMINE; DESENSITIZATION; RATS; SYSTEM AB Incubation of the C6 cells with 10 muM idazoxan (an alpha2-adrenoceptor antagonist and putative antidepressant) for 5 days in vitro resulted in a 23% reduction of beta-adrenoceptor number and a 37% decrease in isoproterenol-induced cyclic AMP accumulation. In contrast, post-receptor stimulated cyclic AMP accumulation (by the use of forskolin or cholera toxin) was unaffected. The desensitization of the beta-adrenoceptor was accompanied by an increase in the K(L)/K(H) ratio for this receptor. Chronic in vitro treatment of C6 glioma cells with idazoxan did not significantly affect cholera or pertussis toxin catalyzed ribosylation of Gs and Gi/Go in these cells. Similarly, idazoxan did not alter either the basal levels of protein kinase C (PKC) alpha, or its cytoplasm to membrane translocation. These results suggest that idazoxan may have direct postsynaptic effects, the site of which may be at the level of receptor/G protein interaction. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP MANJI, HK (reprint author), NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,BLDG 10,ROOM 2D46,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Chen, Guang/A-2570-2017 NR 43 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD NOV 2 PY 1992 VL 227 IS 3 BP 275 EP 282 DI 10.1016/0922-4106(92)90005-G PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JV992 UT WOS:A1992JV99200005 PM 1361912 ER PT J AU KOONIN, EV AF KOONIN, EV TI THE 2ND CHOLERA-TOXIN, ZOT, AND ITS PLASMID-ENCODED AND PHAGE-ENCODED HOMOLOGS CONSTITUTE A GROUP OF PUTATIVE ATPASES WITH AN ALTERED PURINE NTP-BINDING MOTIF SO FEBS LETTERS LA English DT Article DE ZOT PROTEIN; SECOND CHOLERA TOXIN; NTP-BINDING MOTIF; ATPASE; FILAMENTOUS PHAGE GPI ID COMPLETE NUCLEOTIDE-SEQUENCE; PROTEINS; CITRI AB It is shown that the second cholera toxin, Zot, ORF3 product of Pseudomonas plasmid pKB740, and ORF424 product of bacteriophage Pfl are a group of closely related proteins containing a modified version of the purine NTP-binding motif, with a drastic substitution of tyrosine for a conserved glycine. They are distantly but reliably related to the product of gene I of filamentous bacteriophages which is a putative ATPase containing the classical NTP-binding motif and is involved in bacteriophage assembly and exit from the bacterial cell. Hydropathy analysis suggests that the Zot and gene I product may have a similar transmembrane topology. It is hypothesized that Zot may possess ATPase activity and modify the membrane structure of its target cells in an ATP-dependent fashion. Genes for Zot and the related protein of pKB740 are likely to have evolved from gene I of a Pfl-like bacteriophage. RP NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BLDG 38A, 8600 ROCKVILLE PIKE, BETHESDA, MD 20894 USA. NR 21 TC 31 Z9 32 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-5793 EI 1873-3468 J9 FEBS LETT JI FEBS Lett. PD NOV 2 PY 1992 VL 312 IS 1 BP 3 EP 6 DI 10.1016/0014-5793(92)81398-6 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JV998 UT WOS:A1992JV99800002 PM 1426234 ER PT J AU GOLDMAN, D DEAN, M BROWN, GL BOLOS, AM TOKOLA, R VIRKKUNEN, M LINNOILA, M AF GOLDMAN, D DEAN, M BROWN, GL BOLOS, AM TOKOLA, R VIRKKUNEN, M LINNOILA, M TI D2 DOPAMINE RECEPTOR GENOTYPE AND CEREBROSPINAL-FLUID HOMOVANILLIC-ACID, 5-HYDROXYINDOLEACETIC ACID AND 3-METHOXY-4-HYDROXYPHENYLGLYCOL IN ALCOHOLICS IN FINLAND AND THE UNITED-STATES SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE ALCOHOLISM; DOPAMINE; SEROTONIN; GENETIC ASSOCIATION; IMPULSIVITY ID IMPULSIVE FIRE SETTERS; ALLELIC ASSOCIATION; VIOLENT OFFENDERS; NUCLEUS ACCUMBENS; ETHANOL TREATMENT; GENE; METABOLITES; HISTORY; BRAIN AB If a genetic association between the D2 dopamine receptor genotype and alcoholism is mediated by altered dopamine function, then a stronger association might be found in alcoholics who are deviant in indices of dopamine function and by comparing alcoholics to nonalcoholics matched for ethnic origin. Therefore, we evaluated the D2/TaqI polymorphism in 29 impulsive violent alcoholic Finns, 17 nonimpulsive violent alcoholic Finns and 36 Finnish controls free of mental disorders, alcoholism and substance abuse. In 37 of the alcoholics, we measured cerebrospinal fluid (CSF) homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol. There was no relationship between D2/Taq 1 genotype and concentrations of these monoamine metabolites in this group, which exhibits lower CSF HVA and 5-HIAA as compared to controls. There was also no genotypic difference between Finnish alcoholics and nonalcoholic controls. The lack of relationship between D2/Taq1 genotype and HVA concentration was replicated in 24 Caucasian alcoholics in the United States. C1 NIAAA, CLIN STUDIES LAB, BETHESDA, MD 20892 USA. NCI, PROGRAM RESOURCES INC, BETHESDA, MD 20892 USA. UNIV HELSINKI, DEPT PSYCHIAT, SF-00100 HELSINKI 10, FINLAND. RP GOLDMAN, D (reprint author), NIAAA, NEUROGENET LAB,DICBR,9000 ROCKVILLE PIKE,BLDG 10, RM 3C-102, BETHESDA, MD 20892 USA. RI Dean, Michael/G-8172-2012; Goldman, David/F-9772-2010 OI Dean, Michael/0000-0003-2234-0631; Goldman, David/0000-0002-1724-5405 NR 39 TC 89 Z9 90 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD NOV PY 1992 VL 86 IS 5 BP 351 EP 357 DI 10.1111/j.1600-0447.1992.tb03279.x PG 7 WC Psychiatry SC Psychiatry GA KB408 UT WOS:A1992KB40800006 PM 1283042 ER PT J AU ALEXANDER, RC CABIRAC, G LOWENKOPF, T CASANOVA, MF KLEINMAN, J WYATT, RJ KIRCH, DG AF ALEXANDER, RC CABIRAC, G LOWENKOPF, T CASANOVA, MF KLEINMAN, J WYATT, RJ KIRCH, DG TI SEARCH FOR EVIDENCE OF HERPES-SIMPLEX VIRUS, TYPE-1, OR VARICELLA-ZOSTER VIRUS-INFECTION IN POSTMORTEM BRAIN-TISSUE FROM SCHIZOPHRENIC-PATIENTS SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Note DE HERPES SIMPLEX VIRUS; VARICELLA-ZOSTER VIRUS; SCHIZOPHRENIA; POLYMERASE CHAIN REACTION ID COMPLETE DNA-SEQUENCE; SHOPE FIBROMA; ANTIBODY; IMMUNITY; GENOME AB The highly sensitive polymerase chain reaction (PCR) was used to search for herpes simplex virus type 1 (HSV-I) or varicella-zoster virus (VZV) in the DNA extracted from postmortem temporal cortex samples of 8 schizophrenic subjects, 8 nonschizophrenic suicide victims and 8 normal controls. HSV-I or VZV-specific DNA amplification was not detected in any of the samples studied. C1 ROCKY MT MULTIPLE SCLEROSIS CTR, ENGLEWOOD, CO USA. UNIV COLORADO, HLTH SCI CTR, DEPT BIOCHEM BIOPHYS & GENET, DENVER, CO 80262 USA. NIMH, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. NIMH, NEUROPSYCHIAT BRANCH, WASHINGTON, DC 20032 USA. NIMH, DIV CLIN RES, ROCKVILLE, MD 20857 USA. RP ALEXANDER, RC (reprint author), THOMAS JEFFERSON UNIV, DEPT PSYCHIAT & HUMAN BEHAV, 1020 SANSOM ST, THOMPSON BLDG, ROOM 1651, PHILADELPHIA, PA 19107 USA. NR 17 TC 12 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD NOV PY 1992 VL 86 IS 5 BP 418 EP 420 DI 10.1111/j.1600-0447.1992.tb03290.x PG 3 WC Psychiatry SC Psychiatry GA KB408 UT WOS:A1992KB40800017 PM 1336636 ER PT J AU WILEY, CA ACHIM, CL SCHRIER, RD HEYES, MP MCCUTCHAN, JA GRANT, I AF WILEY, CA ACHIM, CL SCHRIER, RD HEYES, MP MCCUTCHAN, JA GRANT, I TI RELATIONSHIP OF CEREBROSPINAL-FLUID IMMUNE ACTIVATION ASSOCIATED FACTORS TO HIV ENCEPHALITIS SO AIDS LA English DT Article DE CYTOKINE; INTERLEUKIN; CEREBROSPINAL FLUID; AIDS; HIV; ENCEPHALITIS ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; TUMOR-NECROSIS-FACTOR; INFECTION; SERUM; CSF; CHILDREN; TYPE-1; BRAIN AB Objectives and design: Because macrophages are the predominant immune cell and the predominant infected cell in the brains of patients with HIV encephalitis, we studied macrophage and immune activation-associated factors in the cerebrospinal fluid (CSF) from 39 autopsied AIDS cases for whom complete neuropathologic evaluation of the brain was available. Results: CSF HIV p24 antigen was present in less than one-third of cases (11 out of 39). Less than half of the autopsies with moderate to severe parenchymal infection by HIV had high levels of CSF p24, although all autopsies with elevated levels of HIV p24 had moderate to severe HIV encephalitis. Elevated levels of cytokines, beta2-microglobulin, neopterin, and quinolinic acid were observed. Conclusions. Although many of the CSF findings showed a strong correlation with each other, none showed a strong correlation with the severity of HIV infection of the brain itself. The absence of a close association between CSF abnormalities and HIV encephalitis could reflect the abundance of complicating opportunistic infections in these terminally ill patients or the inadequacy of CSF as a marker of basal ganglia involvement in HIV encephalitis. These findings complicate interpretation of clinical studies of CSF in patients with AIDS where neuropathologic evaluation is unavailable. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,LA JOLLA,CA 92093. RP WILEY, CA (reprint author), UNIV CALIF SAN DIEGO,DEPT PATHOL,9500 GILMAN DR,BASIC SCI BLDG,ROOM 1055,LA JOLLA,CA 92093, USA. FU NIMH NIH HHS [MH43298, MH45294]; NINDS NIH HHS [NS-25178] NR 33 TC 31 Z9 32 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 NOV PY 1992 VL 6 IS 11 BP 1299 EP 1307 DI 10.1097/00002030-199211000-00010 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JY796 UT WOS:A1992JY79600010 PM 1472335 ER PT J AU ARANDAANZALDO, A ABLASHI, DV VIZA, D AF ARANDAANZALDO, A ABLASHI, DV VIZA, D TI INVITRO REDUCTION OF HIV INFECTIVITY BY DIMETHYLSULFOXIDE SO AIDS LA English DT Letter ID DIMETHYL-SULFOXIDE C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP ARANDAANZALDO, A (reprint author), FAC MED PARIS,IMMUNOBIOL LAB,CNRS,45 RUE ST PERES,F-75006 PARIS,FRANCE. RI Aranda-Anzaldo, Armando/A-6513-2014 OI Aranda-Anzaldo, Armando/0000-0002-5583-5465 NR 9 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD NOV PY 1992 VL 6 IS 11 BP 1402 EP 1403 DI 10.1097/00002030-199211000-00029 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JY796 UT WOS:A1992JY79600029 PM 1472347 ER PT J AU KELLEY, KF VERMUND, SH AF KELLEY, KF VERMUND, SH TI ON THE NATURAL-HISTORY OF HIV AND AIDS IN WOMEN SO AIDS LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; PAPILLOMAVIRUS; INFECTION; NEOPLASIA C1 NIAID,DAIDS,VACCINE TRIALS & EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP KELLEY, KF (reprint author), NEW YORK STATE DEPT HLTH,AIDS EPIDEMIOL PROGRAM,ESP,CORNING TOWER ROOM 722,ALBANY,NY 12237, USA. NR 12 TC 0 Z9 0 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 NOV PY 1992 VL 6 IS 11 BP 1406 EP 1407 DI 10.1097/00002030-199211000-00033 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JY796 UT WOS:A1992JY79600033 PM 1472349 ER PT J AU KORALNIK, IJ LEMP, JF GALLO, RC FRANCHINI, G AF KORALNIK, IJ LEMP, JF GALLO, RC FRANCHINI, G TI INVITRO INFECTION OF HUMAN MACROPHAGES BY HUMAN T-CELL LEUKEMIA LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; ACQUIRED IMMUNODEFICIENCY SYNDROME; LYMPHOMA VIRUS; HUMAN RETROVIRUS; LYMPHOCYTES-T; SYNDROME AIDS; ANTIBODIES; TRANSFORMATION; MYELOPATHY; EXPRESSION AB HTLV-I is associated with a neurological syndrome designated Tropical Spastic Paraparesis/HTLV-I associated myelopathy (TSP/HAM). To determine whether HTLV-I can replicate in human primary macrophages and thus contribute to HTLV-I dissemination in the nervous system, elutriated human macrophages were infected cell-free with the HTLV-I(CR) and HTLV-I(BOU) isolates from patients with adult T-cell leukemia and TSP/HAM, respectively. Viral production was monitored by measuring the viral p24 gag antigen in the cell culture supernatant, by electron microscopy (EM) and by polymerase chain reaction (PCR) on viral DNA and RNA. The HTLV-I p24 gag antigen was detected 21 days after infection with either isolate, and the presence of mature viral particles was demonstrated by electron microscopy one month after infection. Viral sequences were amplified by PCR analysis of the infected macrophages' DNA. Spliced mRNAs for the p40tax and p27rex proteins, as well as the p12I, and p30II proteins encoded by the pX region were readily identified by reverse transcriptase PCR. Altogether, these data indicate that HTLV-I replication occurs in vitro in primary human macrophages. Whether macrophage infection occurs also in vivo and is a crucial step in the induction of the neurological manifestations observed in TSP/HAM remains an open question. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOTECHNOL INC,COLUMBIA,MD 21046. RP FRANCHINI, G (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 34 TC 60 Z9 60 U1 0 U2 1 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 NOV PY 1992 VL 8 IS 11 BP 1845 EP 1849 DI 10.1089/aid.1992.8.1845 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA KC513 UT WOS:A1992KC51300001 PM 1489573 ER PT J AU WATSON, RR GOTTESFELD, Z AF WATSON, RR GOTTESFELD, Z TI 7 PAPERS FROM A SYMPOSIUM ON ALCOHOL AND IMMUNOMODULATION SPONSORED BY THE INTERNATIONAL-SOCIETY-FOR-BIOMEDICAL-RESEARCH-ON-ALCOHOLISM SO ALCOHOL LA English DT Editorial Material C1 UNIV TEXAS,SCH MED,DEPT NEUROBIOL & ANAT,HOUSTON,TX 77225. RP WATSON, RR (reprint author), UNIV ARIZONA,ARIZONA HLTH SCI CTR,NIAAA,ALCOHOL RES CTR,1501 N CAMPBELL AVE,TUCSON,AZ 85724, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV-DEC PY 1992 VL 9 IS 6 BP 453 EP 454 DI 10.1016/0741-8329(92)90079-P PG 2 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA JZ040 UT WOS:A1992JZ04000001 ER PT J AU PIROZHKOV, SV WATSON, RR CHEN, GJ AF PIROZHKOV, SV WATSON, RR CHEN, GJ TI ETHANOL ENHANCES IMMUNOSUPPRESSION INDUCED BY COCAINE SO ALCOHOL LA English DT Article; Proceedings Paper CT SYMP ON ALCOHOL AND IMMUNOMODULATION CY JUN 21, 1992 CL BRISTOL, ENGLAND SP INT SOC BIOMED RES ALCOHOLISM DE COCAINE; CONCANAVALIN-A; CYTOKINES; ETHANOL ID GAMMA-INTERFERON-PRODUCTION; BETA-ENDORPHIN; LYMPHOCYTE SUBSETS; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; HIV INFECTION; BALB/C MICE; PHARMACOKINETICS; CORTICOTROPIN; COCAETHYLENE AB Use of cocaine concurrently with alcohol is prevalent among cocaine addicts. Cocaine has been shown to inhibit phytohemagglutinin- and ConA-induced proliferation of T-lymphocytes, NK cell cytotoxicity, and phagocytic activity of peritoneal macrophages. In some studies no effects of cocaine on the immune response have been observed, although on the contrary, others show it increased the NK cell activity and serum antibody response to T-dependent antigen. Effects of cocaine on the immune system may be mediated by its neurostimulatory action on the hypothalamo-pituitary-adrenal axis. ACTH, beta-endorphine, and corticosterone released under the action of cocaine exert various inhibitory effects on the immune function. We studied the immunotoxic effect of cocaine, combination of cocaine with ethanol, and cocaethylene, a derivative formed from cocaine and ethanol in the body, on the mitogen-stimulated production of cytokines by splenocytes. C57BL mice were injected twice daily with 20 mg/kg cocaine or equivalent dose of cocaethylene and received a liquid Lieber-DeCarli diet containing ethanol (26% of total calories) or isocaloric amount of maltose-dextrin. After 3 weeks of treatment, cocaine and cocaethylene caused a significant decrease of the spleen weight and total number of splenocytes. In splenocytes isolated from the cocaine- or cocaethylene-treated mice, mitogen-stimulated production of gamma-interferon, tumor necrosis factor, and interleukin-2 was suppressed, in all cases more severely when cocaethylene was used. Thus, formation of cocaethylene during simultaneous consumption of cocaine and ethanol may enhance the immunotoxicity of cocaine. C1 UNIV ARIZONA,ARIZONA HLTH SCI CTR,NIAAA,ALCOHOL RES CTR,DEPT FAMILY & COMMUNITY MED,TUCSON,AZ 85724. MOSCOW MEDICO BIOL PROBLEMS ADDICT RES INST,MOSCOW,USSR. FU NIAAA NIH HHS [AA 08037]; NIDA NIH HHS [DA 04827] NR 48 TC 16 Z9 16 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV-DEC PY 1992 VL 9 IS 6 BP 489 EP 494 DI 10.1016/0741-8329(92)90085-O PG 6 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA JZ040 UT WOS:A1992JZ04000007 PM 1472304 ER PT J AU MAUTNER, GC BEREZOWSKI, K MAUTNER, SL ROBERTS, WC AF MAUTNER, GC BEREZOWSKI, K MAUTNER, SL ROBERTS, WC TI DEGREES OF CORONARY ARTERIAL NARROWING AT NECROPSY IN MEN WITH LARGE FUSIFORM ABDOMINAL AORTIC-ANEURYSM SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DISEASE; REPAIR; RISK; POPULATION; MANAGEMENT; DEATH AB In 27 patients (mean age at death 72 +/- 9 years) with abdominal aortic aneurysm (AAA) greater-than-or-equal-to 5.0 cm in its widest transverse diameter, the amounts of narrowing at necropsy in the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries were determined. During life, 12 of the 27 patients (44%) had symptoms of myocardial ischemia: angina pectoris alone in 2, acute myocardial infarction alone in 3, angina pectoris and acute myocardial infarction in 5, and sudden coronary death in 2. Ten of the 27 patients (37%) died from consequences of myocardial ischemia. Six (22%) died from rupture of the AAA. Grossly visible left ventricular necrosis or fibrosis, or both, was present in 15 patients (56%). Of the 27 patients, 23 (85%) had narrowing 76 to 100% in cress-sectional area of 1 or more major coronary arteries by atherosclerotic plaque. The mean number of coronary arteries per patient severely (>75%) narrowed was 2.0 +/- 1.3/4.0. Of the 108 major coronary arteries in the 27 patients, 55 (51%) were narrowed >75% in cross-sectional area by plaque. The 4 major coronary arteries in the 27 patients were divided into 5-mm segments and a histologic section, stained by the Movat method, was prepared from each segment. The mean percentages of the resulting 1,475 five-mm segments narrowed in cross-sectional area 0 to 25%, 26 to 50%, 51 to 75%, 76 to 95% and 96 to 100% were 17, 37, 28, 15 and 3%, respectively. The percentages of 5-mm coronary segments narrowed >75% in cross-sectional area were similar in the right, left anterior descending, and left circumflex coronary arteries. Thus, patients with AAA nearly always have diffuse and severe coronary atherosclerosis. RP MAUTNER, GC (reprint author), NHLBI,PATHOL PROGRAM,BLDG 10,ROOM 2N258,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 13 Z9 13 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 NOV 1 PY 1992 VL 70 IS 13 BP 1143 EP 1146 DI 10.1016/0002-9149(92)90045-Z PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW285 UT WOS:A1992JW28500009 PM 1414936 ER PT J AU MAUTNER, GC MAUTNER, SL ROBERTS, WC AF MAUTNER, GC MAUTNER, SL ROBERTS, WC TI AMOUNTS OF CORONARY ARTERIAL NARROWING BY ATHEROSCLEROTIC PLAQUE AT NECROPSY IN PATIENTS WITH LOWER-EXTREMITY AMPUTATION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PERIPHERAL VASCULAR-DISEASE; MANAGEMENT; DEATH; RISK AB In 26 patients (mean age at death 68 +/- 9 years) who had undergone amputation (at mean age 63 +/-12 years) of 1 or both lower extremities due to severe peripheral arterial atherosclerosis, the amounts of narrowing at necropsy in the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries were determined. During life, 15 of the 26 patients (58%) had symptoms of myocardial ischemia: angina pectoris alone in 1, acute myocardial infarction alone in 5, and angina and/or infarction plus congestive heart failure or sudden coronary death in 9. Twelve of the 26 patients (42%) died from consequences of myocardial ischemia: acute myocardial infarction in 5, sudden coronary death in 3, chronic congestive heart failure in 3, and shortly after coronary bypass surgery in 1. Grossly visible left ventricular necrosis or fibrosis, or both, was present in 21 patients (81%). Of the 26 patients, 24 (92%) had narrowing 76 to 100% in cross-sectional area of 1 or more major coronary arteries by atherosclerotic plaque. The mean number of coronary arteries per patient severely (>75%) narrowed was 2.3 +/- 1.0/4.0. Of the 104 major coronary arteries in the 26 patients, 60 (58%) were narrowed >75% in cross-sectional area by plaque. The 4 major coronary arteries in the 26 patients were divided into 5-mm segments and a histologic section, stained by the Movat method, was prepared from each segment. The mean percentages of the resulting 1,322 five-mm segments narrowed in cross-sectional area 0 to 25%, 26 to 50%, 51 to 75%, 76 to 95% and 96 to 100% were 17, 20, 35, 19 and 9%, respectively. The percentages of 5-mm coronary segments narrowed >75% in cross-sectional area were similar in the left anterior descending, left circumflex and right coronary arteries. Thus, patients with peripheral arterial atherosclerosis severe enough to warrant amputation nearly always have diffuse and severe coronary atherosclerosis at the time of necropsy. RP MAUTNER, GC (reprint author), NHLBI,PATHOL PROGRAM,BLDG 10,ROOM 2N-258,BETHESDA,MD 20892, USA. NR 17 TC 40 Z9 41 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 NOV 1 PY 1992 VL 70 IS 13 BP 1147 EP 1151 DI 10.1016/0002-9149(92)90046-2 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW285 UT WOS:A1992JW28500010 PM 1414937 ER PT J AU LAUER, MS EVANS, JC LEVY, D AF LAUER, MS EVANS, JC LEVY, D TI PROGNOSTIC IMPLICATIONS OF SUBCLINICAL LEFT-VENTRICULAR DILATATION AND SYSTOLIC DYSFUNCTION IN MEN FREE OF OVERT CARDIOVASCULAR-DISEASE (THE FRAMINGHAM HEART-STUDY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SIZE; MASS; ECHOCARDIOGRAPHY; SURVIVAL; RECOVERY; VOLUME AB To determine the prognostic significance of asymptomatic left ventricular (LV) dilatation and LV systolic dysfunction, 1,493 men who were free of symptomatic cardiovascular disease underwent M-mode echocardiography and were then followed for a mean of 4.15 years. At baseline examination, 170 men (11.4%) had an abnormally high end-diastolic LV internal dimension (greater-than-or-equal-to 56 mm) and 76 (5.1%) had an abnormally low fractional shortening (less-than-or-equal-to 30%). During the follow-up period, 68 men experienced 92 cardiovascular disease events. After adjusting for age and traditional cardiovascular disease risk factors in proportional-hazards analyses, fractional shortening was a significant independent predictor of cardiovascular risk (relative risk [RR] = 1.42, 95% confidence interval [CI] 1.12 to 1.81, for decrease of fractional shortening by 4%). Increased risk was also associated with combinations of low fractional shortening and high end-diastolic internal dimension (RR = 3.77, 95% CI 1.59 te 8.93) and with low percent fractional shortening with LV hypertrophy (RR = 5.93, 95% CI 1.97 to 17.85). In conclusion, subclinical LV dilatation and LV systolic dysfunction, although uncommon in men free of overt cardiovascular disease, are associated with increased risk for new cardiovascular disease events. C1 NHLBI,FRAMINGHAM HEART STUDY,5 THURBER ST,FRAMINGHAM,MA 01701. LAHEY CLIN MED CTR,CARDIOL SECT,BURLINGTON,VT. BETH ISRAEL HOSP,DIV CARDIOL & CLIN EPIDEMIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. CHARLES A DANA RES INST,DIV CARDIOVASC,BOSTON,MA. BETH ISRAEL HOSP,DEPT MED,HARVARD THORNIKE LAB,BOSTON,MA 02215. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 FU NHLBI NIH HHS [HL07374, N01-HC-38038] NR 23 TC 95 Z9 96 U1 0 U2 1 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 NOV 1 PY 1992 VL 70 IS 13 BP 1180 EP 1184 DI 10.1016/0002-9149(92)90052-Z PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW285 UT WOS:A1992JW28500016 PM 1414943 ER PT J AU GREINER, TC BURNS, CP DICK, FR HENRY, KM MAHMOOD, I AF GREINER, TC BURNS, CP DICK, FR HENRY, KM MAHMOOD, I TI CONGENITAL DYSERYTHROPOIETIC ANEMIA TYPE-II DIAGNOSED IN A 69-YEAR-OLD PATIENT WITH IRON OVERLOAD SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID ELECTRON; DEFECT AB Congenital dyserythropoietic anemia type II is a rare disorder that is often diagnosed in patients before age 20 years. Patients with this disorder, which is also called hereditary erythroblastic multinuclearity associated with a positive acidified serum lysis test, may have symptoms of iron overload. The purpose of this case report is to alert physicians to consider the diagnosis of congenital dyserythropoietic anemia type II in elderly patients who have anemia and iron overload. C1 UNIV IOWA,COLL MED,DEPT PATHOL,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT INTERNAL MED,IOWA CITY,IA 52242. RP GREINER, TC (reprint author), NCI,PATHOL LAB,BLDG 10,RM 2N113,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 1992 VL 98 IS 5 BP 522 EP 525 PG 4 WC Pathology SC Pathology GA JW894 UT WOS:A1992JW89400009 PM 1485605 ER PT J AU BURCHFIEL, CM SHETTERLY, SM BAXTER, J HAMMAN, RF AF BURCHFIEL, CM SHETTERLY, SM BAXTER, J HAMMAN, RF TI THE ROLES OF INSULIN, OBESITY, AND FAT DISTRIBUTION IN THE ELEVATION OF CARDIOVASCULAR RISK-FACTORS IN IMPAIRED GLUCOSE-TOLERANCE - THE SAN LUIS VALLEY DIABETES STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ADIPOSE TISSUE; CARDIOVASCULAR DISEASES; GLUCOSE TOLERANCE TEST; HISPANIC AMERICANS; INSULIN; OBESITY; RISK FACTORS ID SYMPATHETIC NERVOUS-SYSTEM; BLOOD-PRESSURE; BODY FATNESS; URIC-ACID; MELLITUS; DISEASE; HYPERINSULINEMIA; HYPERTENSION; POPULATION; RESISTANCE AB The objective of this study was to determine whether a less favorable risk factor pattern for cardiovascular disease among persons with impaired glucose tolerance could be explained by fasting insulin, obesity, and/or a central distribution of body fat. Between 1984 and 1988, cardiovascular risk factors were examined cross-sectionally in Hispanic and non-Hispanic white participants in the San Luis Valley Diabetes Study who had either impaired (n = 173) or normal (n = 1,107) glucose tolerance. Sex-specific analysis of covariance models were constructed to adjust risk factor levels for age, age and insulin, and age, insulin, body mass index, and centrality index. Both males and females with impaired glucose tolerance had higher age-adjusted mean diastolic blood pressures, heart rates, uric acid levels, and triglyceride levels and lower levels of high density lipoprotein (HDL) cholesterol and HDL3 cholesterol than normal subjects; differences were significant for all risk factors except HDL cholesterol and HDL3 cholesterol in males. Differences in diastolic blood pressure in males, and differences in heart rate and triglyceride in both sexes, remained significant after adjustment for all covariates. However, differences in uric acid in males and differences in diastolic blood pressure and HDL3 cholesterol in females were attenuated to borderline significance levels. Differences in uric acid and HDL cholesterol in females were diminished to nonsignificant levels, especially after adjustment tor obesity-related measures. With few exceptions, fasting insulin did not appear to play a major role in accounting for differences in these risk factors. With adjustment, ethnic differences (Hispanic vs. non-Hispanic white) were smaller and were statistically significant less often than differences observed between impaired and normal glucose tolerant groups. The authors concluded that hyperinsulinemia, obesity, and a central body fat distribution accounted for some, but usually not all, of the less favorable cardiovascular risk factor pattern found in subjects with impaired glucose tolerance. C1 UNIV COLORADO, SCH MED, DEPT PREVENT MED & BIOSTAT, DENVER, CO 80262 USA. RP HAMMAN, RF (reprint author), NHLBI, HONOLULU HEART PROGRAM, HONOLULU, HI USA. FU NCRR NIH HHS [CRC-RR00051]; NIDDK NIH HHS [DK-30747] NR 57 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1992 VL 136 IS 9 BP 1101 EP 1109 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KD183 UT WOS:A1992KD18300007 PM 1462970 ER PT J AU FREEDMAN, LS SCHATZKIN, A AF FREEDMAN, LS SCHATZKIN, A TI SAMPLE-SIZE FOR STUDYING INTERMEDIATE END-POINTS WITHIN INTERVENTION TRIALS OR OBSERVATIONAL STUDIES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ADENOMA; BIOLOGICAL MARKERS; COLONIC NEOPLASMS; COLONIC POLYPS; DIET THERAPY; RISK FACTORS ID COLON CANCER; END-POINTS; POLYPS; RECURRENCE; FIBER; RISK AB An intermediate endpoint is a biologic event or marker that is a precursor to a given health outcome. Examples of potential intermediate endpoints include serum cholesterol for coronary heart disease, endogenous steroid hormones for breast cancer, and CD4 count for acquired immunodeficiency syndrome. When one is studying a potential intermediate endpoint in the context of an intervention trial, five types of questions may be investigated: 1) Does the intervention affect the intermediate endpoint? 2) Is the intermediate endpoint associated with prognostic or risk factors? 3) Is the intermediate endpoint associated with the main outcome? 4) Is the intervention effect on the main outcome mediated by the intermediate endpoint? 5) Are the prognostic or risk factor effects mediated by the intermediate endpoint? In this paper, the authors show that each of these questions has different sample size requirements, and they illustrate their point with a discussion of an ancillary study of large bowel epithelial proliferation in the National Cancer Institute's Polyp Prevention Trial. The same methods may be used in an observational study, in which case questions 2, 3, and 5 are relevant. However, much larger numbers than those used in the Polyp Prevention Trial example will be required when the main outcome is rare. C1 NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. RP FREEDMAN, LS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 25 TC 141 Z9 146 U1 0 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1992 VL 136 IS 9 BP 1148 EP 1159 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KD183 UT WOS:A1992KD18300013 PM 1462974 ER PT J AU SILVERMAN, DT HOOVER, RN AF SILVERMAN, DT HOOVER, RN TI TESTS FOR TREND AND DOSE-RESPONSE - MISINTERPRETATIONS AND ALTERNATIVES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP SILVERMAN, DT (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 3 TC 2 Z9 2 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 1992 VL 136 IS 9 BP 1172 EP 1172 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KD183 UT WOS:A1992KD18300020 PM 1462979 ER PT J AU HECHT, JT BLANTON, SH WANG, YP DAIGER, SP HORTON, WA RHODES, C YAMADA, Y FRANCOMANO, CA AF HECHT, JT BLANTON, SH WANG, YP DAIGER, SP HORTON, WA RHODES, C YAMADA, Y FRANCOMANO, CA TI EXCLUSION OF HUMAN PROTEOGLYCAN LINK PROTEIN (CRTL1) AND TYPE-II COLLAGEN (COL2A1) GENES IN PSEUDOACHONDROPLASIA SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article ID DEFECT AB Patients with pseudoachondroplasia have a skeletal dysplasia with marked short stature. The most common cause of this condition is an autosomal dominant mutation, although autosomal recessive inheritance has been reported. Linkage to 2 cartilage-specific candidate genes, type Il collagen (COL2A1) and proteoglycan link protein genes (CRTL1), was tested in 9 autosomal dominant families with pseudoachondroplasia. Tight linkage to these candidate genes was excluded with LOD scores for COL2A1 of - 2A5 at theta = 0.05 and for CRTL1 of - 7.28 at theta = 0.001. Discordant inheritance of the disease phenotype with each of these genes was also observed. Thus, these 2 candidate genes can be excluded as the cause of disease in these families. C1 JOHNS HOPKINS UNIV,SCH MED,GRAD SCH BIOMED SCI,BALTIMORE,MD 21218. NATL INST DENTAL RES,BETHESDA,MD. RP HECHT, JT (reprint author), UNIV TEXAS,HLTH SCI CTR,SCH MED,DEPT PEDIAT,POB 20708,HOUSTON,TX 77225, USA. FU NEI NIH HHS [EY07142]; NIDCR NIH HHS [R03DE09189-01] NR 23 TC 10 Z9 10 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 1 PY 1992 VL 44 IS 4 BP 420 EP 424 DI 10.1002/ajmg.1320440406 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA JV049 UT WOS:A1992JV04900005 PM 1442879 ER PT J AU OERTER, KE FRIEDMAN, TC ANDERSON, HC CASSORLA, FG AF OERTER, KE FRIEDMAN, TC ANDERSON, HC CASSORLA, FG TI FAMILIAL SYNDROME OF ENDOCRINE AND NEUROECTODERMAL ABNORMALITIES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE ACANTHOSIS NIGRICANS; ALOPECIA, GONADOTROPINS; GROWTH HORMONE; ICHTHYOSIS-VULGARIS; MENTAL RETARDATION; PILI-TORTI; PUBERTY; SENSORI-NEURAL DEAFNESS; TYPE-II DIABETES-MELLITUS ID HYPOGONADISM; ALOPECIA; DEAFNESS AB We report on a previously undescribed combination of endocrine and neuroectodermal abnormalities in four sibs from Burma. These abnormalities include low growth hormone levels in response to provocative stimuli, delayed puberty associated with prepubertal levels of gonadotropins in the males and pubertal levels of gonadotropins in the females, type Il diabetes mellitus with elevated insulin levels, mild mental retardation, sensori-neural deafness, and alopecia without pili torti. They also had a characteristic facial appearance and fleshy hands and feet. This family appears to have a previously undescribed combination of endocrine and neuroectodermal abnormalities. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 12 TC 6 Z9 6 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 1 PY 1992 VL 44 IS 4 BP 487 EP 491 DI 10.1002/ajmg.1320440421 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA JV049 UT WOS:A1992JV04900020 PM 1442893 ER PT J AU BRINTON, LA BERMAN, ML MORTEL, R TWIGGS, LB BARRETT, RJ WILBANKS, GD LANNOM, L HOOVER, RN AF BRINTON, LA BERMAN, ML MORTEL, R TWIGGS, LB BARRETT, RJ WILBANKS, GD LANNOM, L HOOVER, RN TI REPRODUCTIVE, MENSTRUAL, AND MEDICAL RISK-FACTORS FOR ENDOMETRIAL CANCER - RESULTS FROM A CASE-CONTROL STUDY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ENDOMETRIAL CANCER; REPRODUCTION; MENSTRUATION; OBESITY; DIABETES ID BODY-FAT DISTRIBUTION; INFERTILE WOMEN; EPIDEMIOLOGY; ESTROGENS; CARCINOMA AB OBJECTIVE: Our objective was to evaluate the risk for endometrial cancer in relation to reproductive, menstrual, and medical factors. STUDY DESIGN: A case-control study of 405 endometrial cancer cases and 297 population controls in five areas of the United States enabled risk to be evaluated. RESULTS: A major risk factor was the absence of prior pregnancy (relative risk 2.8, 95% confidence interval 1.7 to 4.6). The protective effect of pregnancy appeared to reflect the influence of term births, because spontaneous and induced abortions were unrelated risk. Among nulliparous women infertility was a significant factor, with women having sought medical advice having nearly eight times the risk of those without difficulty conceiving. After adjustment for other reproductive characteristics, age at first birth and duration of breast-feeding were not related to risk. CONCLUSIONS: Elevated risks were found for subjects reporting early ages at menarche (relative risk 2.4 for ages < 12 vs greater-than-or-equal-to 15) and longer days of flow (relative risk 1.9 for greater-than-or-equal-to 7 vs < 4 days), but there was no relationship with late ages at natural menopause. Height was not associated with risk, but there was a significant relation to weight, with the risk for 200 versus < 125 pounds being 7.2 (95% confidence interval 3.9 to 13.3). After adjustment for weight and other factors, histories of hypertension and gallbladder disease were not significantly related to risk, but an effect of diabetes persisted (relative risk 2.0, 95% confidence interval 1.1 to 3.6). Hirsutism developing at older ages was also significantly related (relative risk 2.0, 95% confidence interval 1.2 to 3.4). C1 RUSH MED COLL,DEPT OBSTET & GYNECOL,CHICAGO,IL 60612. WESTAT CORP,ROCKVILLE,MD. UNIV CALIF IRVINE,MED CTR,DEPT OBSTET & GYNECOL,IRVINE,CA 92717. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT OBSTET & GYNECOL,HERSHEY,PA 17033. UNIV MINNESOTA,HLTH SCI CTR,DEPT OBSTET & GYNECOL,MINNEAPOLIS,MN 55455. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC 27103. RP BRINTON, LA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 25 TC 217 Z9 217 U1 0 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 1992 VL 167 IS 5 BP 1317 EP 1325 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JZ241 UT WOS:A1992JZ24100021 PM 1442985 ER PT J AU VILLAR, J COGSWELL, M KESTLER, E CASTILLO, P MENENDEZ, R REPKE, JT AF VILLAR, J COGSWELL, M KESTLER, E CASTILLO, P MENENDEZ, R REPKE, JT TI EFFECT OF FAT AND FAT-FREE MASS DEPOSITION DURING PREGNANCY ON BIRTH-WEIGHT SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE BIRTH WEIGHT; FAT DEPOSITION; BODY COMPOSITION CHANGES DURING PREGNANCY ID PERINATAL DATA; BODY-FAT; WOMEN; LACTATION AB OBJECTIVES: The purposes of our study were to describe the patterns and location of fat and fat-free mass deposition during pregnancy and to evaluate their effects on fetal growth. STUDY DESIGN: Our study is a prospective follow-up of 105 healthy pregnant women who were delivered of term infants. Body composition was evaluated eight times during gestation with anthropometric measures and bioimpedance techniques. Body fat and fat-free mass were calculated with equations specifically developed for this population. RESULTS: Total weight gain was 10.0 +/- 3.5 kg; net weight gain was 3.7 +/- 0.31 kg; birth weight was 3211 +/- 467 gm (values are mean +/- SEM). In these women fat was deposited mostly in the thigh and subscapular region for a total of 6.23 +/- 0.19 kg at term. The period of pregnancy of the largest maternal fat deposition per week is between the twentieth and thirtieth weeks. After adjusting by prepregnancy weight, birth weight is associated with maternal changes in thigh skin folds and fat gain before the thirtieth week of gestation. Infants born to mothers with low fat gain before the thirtieth week were 204 gm lighter than infants born to mothers with fat gain greater-than-or-equal-to 25th percentile of this population. CONCLUSION: Maternal nutritional status at the beginning of gestation and the rate of fat gain early in pregnancy are the two nutritional indicators most strongly associated with fetal growth in this population. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV HOSP,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21205. NICHHD,DIV PREVENT RES,BALTIMORE,MD 21224. GUATEMALAN SOCIAL SECUR OBSTET & GYNECOL HOSP,IGSS,GUATEMALA CITY,GUATEMALA. NR 29 TC 86 Z9 88 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 1992 VL 167 IS 5 BP 1344 EP 1352 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JZ241 UT WOS:A1992JZ24100026 PM 1442988 ER PT J AU SCHELLER, JM AF SCHELLER, JM TI PRETERM VERSUS TERM ASPHYXIA SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter ID CEREBRAL-PALSY; RISK RP SCHELLER, JM (reprint author), NIH,PUBL HLTH SERV,DEPT HLTH & HUMAN SERV,ROOM 714,FED BLDG,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 1992 VL 167 IS 5 BP 1481 EP 1481 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JZ241 UT WOS:A1992JZ24100055 PM 1443008 ER PT J AU CAMPO, E MONTEAGUDO, C CASTRONOVO, V CLAYSMITH, AP FERNANDEZ, PL SOBEL, ME AF CAMPO, E MONTEAGUDO, C CASTRONOVO, V CLAYSMITH, AP FERNANDEZ, PL SOBEL, ME TI DETECTION OF LAMININ RECEPTOR MESSENGER-RNA IN HUMAN CANCER CELL-LINES AND COLORECTAL TISSUES BY INSITU HYBRIDIZATION SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FIBRO-SARCOMA CELLS; TUMOR-CELLS; BASEMENT-MEMBRANE; CARCINOMA-CELLS; METASTASIS; EXPRESSION; SEQUENCE; PROTEIN; IDENTIFICATION; ESTABLISHMENT AB The 67-kd high-affinity laminin receptor (67 LR) is a gene product whose expression appears to be associated with the invasive and metastatic phenotype of a variety of human cancer cells. Northern blot hybridization bas been routinely used to quantify the level of 67 LR mRNA from total cellular RNA extracts homogenized tissue specimens or in vitro grown cell populations. This technique is useful to assess the average expression of the 67 LR mRNA of a particular sample but does not provide information about expression in specific cell types nor about heterogeneity of expression from cell to cell In this study, we analyzed the expression of 67 LR mRNA in four human cancer cell lines with varying degrees of expression 67 LR protein (renal cancer A-704, breast carcinoma MCF-7/4 and MCF-7/7, and pancreatic cancer Panc-1) using in situ hybridization performed with 67 LR riboprobes. Total cellular RNA was simultaneously extracted from the cell lines and hybridized on Northern blots with a 67 LR cDNA probe to assess the validity of the mRNA detection by in situ hybridization Sixty-seven LR mRNA expression was higher in Panc-1 and MCF-7/4 cells than in MCF-7/7 and renal carcinoma A-704. There was a direct correlation (R2 = 0.88) between the in situ hybridization analysis and the mRNA levels detected by Northern blot analysis. The in situ hybridization method showed a heterogeneous expression of the 67 LR mRNA in the four cell lines with different subpopulations of cells showing a range from negative to high levels of the message. Sixteen freshly frozen human colorectal tissues (seven adenocarcinomas, five matched normal mucosae, and four adenomas) were also analyzed by in situ hybridization The 67 LR mRNA was localized in normal and neoplastic epithelial cells. Adenocarcinoma cells showed a 1.6- to 5-fold higher expression (P < 0.02 according to the Wilcoxon-Mann-Whitney test) than did epithelial colonic cells from normal mucosae or adenomas. The signal tended to be stronger in poorly differentiated carcinomas and carcinomas with metastases than in moderately differentiated and nonmetastatic tumors. We conclude that the high expression of 67LR mRNA in colorectal tumors is due to an increased production by tumor cells. Furthermore, in situ hybridization is an effective method to detect the expression of LR mRNA in cultured cell lines as well as in frozen tissue sections. C1 NCI,PATHOL LAB,BLDG 10,RM 2A33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Monteagudo, Carlos/H-6555-2016; OI Campo, elias/0000-0001-9850-9793 NR 46 TC 28 Z9 29 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1992 VL 141 IS 5 BP 1073 EP 1083 PG 11 WC Pathology SC Pathology GA JX306 UT WOS:A1992JX30600009 PM 1443045 ER PT J AU CZUB, S DURAY, PH THOMAS, RE SCHWAN, TG AF CZUB, S DURAY, PH THOMAS, RE SCHWAN, TG TI CYSTITIS INDUCED BY INFECTION WITH THE LYME-DISEASE SPIROCHETE, BORRELIA-BURGDORFERI, IN MICE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID WHITE-FOOTED MICE; INTERSTITIAL CYSTITIS; PEROMYSCUS-LEUCOPUS; MONOCLONAL-ANTIBODY; TREPONEMA-PALLIDUM; URINARY-BLADDER; SYRIAN-HAMSTERS; LABORATORY MICE; ARTHRITIS; HISTOPATHOLOGY AB Previous studies have demonstrated that the urinary bladder is a consistent source for isolating the Lyme disease spirochete, Borrelia burgdorferi, from both experimentally infected and naturally exposed rodents. We examined histopathologic changes in the urinary bladder of different types of rodents experimentally infected with Lyme spirochetes, including BALB/c mice (Mus musculus), nude mice (M. musculus), white-footed mice (Peromyscus leucopus), and grasshopper mice (Onychomys leucogaster). Animals were inoculated intraperitoneally, subcutaneously, or intranasally with low-passaged spirochetes, high-passaged spirochetes, or phosphate-buffered saline. At various times after inoculation, animals were killed and approximately one-half of each urinary bladder and kidney were cultured separately in BSK-II medium while the other half of each organ was prepared for histologic examination. Spirochetes were cultured from the urinary bladder of all 35 mice inoculated with low-passaged spirochetes while we were unable to isolate spirochetes from any kidneys of the same mice. The pathologic changes observed most frequently in the urinary bladder of the infected mice were the presence of lymphoid aggregates, vascular changes, including an increase in the number of vessels and thickening of the vessel walls, and perivascular infiltrates. Our results demonstrate that nearly all individuals (93%) of the four types of mice examined had a cystitis associated with spirochetal infection. C1 NIAID,DEPT HLTH & HUMAN SERV,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. NR 45 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1992 VL 141 IS 5 BP 1173 EP 1179 PG 7 WC Pathology SC Pathology GA JX306 UT WOS:A1992JX30600017 PM 1443051 ER PT J AU ROPER, M SMITH, MA SONDEL, PM GILLESPIE, A REAMAN, GH HAMMOND, GD LEVITT, D ROSOLEN, A COLAMONICI, OR NECKERS, LM POPLACK, DG AF ROPER, M SMITH, MA SONDEL, PM GILLESPIE, A REAMAN, GH HAMMOND, GD LEVITT, D ROSOLEN, A COLAMONICI, OR NECKERS, LM POPLACK, DG TI A PHASE-I STUDY OF INTERLEUKIN-2 IN CHILDREN WITH CANCER SO AMERICAN JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE INTERLEUKIN-2; PEDIATRIC PHASE-I TRIAL; BIOLOGIC THERAPY; IMMUNOLOGICAL MODULATION ID ACTIVATED KILLER-CELLS; BONE-MARROW TRANSPLANTATION; HIGH-DOSE INTERLEUKIN-2; HUMAN RECOMBINANT INTERLEUKIN-21; ANTIGANGLIOSIDE GD2 ANTIBODY; TOXICITY GENERATED INVIVO; COLONY-STIMULATING FACTOR; MINIMAL RESIDUAL DISEASE; CELLULAR CYTO-TOXICITY; NEURO-BLASTOMA AB Recombinant interleukin-2 (IL-2) produces clinical responses in approximately 20% of adult patients with renal cell carcinoma and melanoma, with both high-dose bolus and continuous infusion regimens. Because of the lower toxicity of continuous infusion, we elected to investigate in a Phase I trial a 5-day continuous infusion repeated for three weeks in children with malignancies refractory to standard therapy. Nineteen children with solid tumors and eight children with hematologic malignancies were entered into the study. The maximum tolerated dose was 3 x 10(6) U/m2/day, with dose-limiting toxicities occurring in five of seven patients treated at the 5 x 10(6) U/m2/day dose level. Dose-limiting toxicities included hypotension, hyperbilirubinemia, thrombocytopenia, pulmonary/pleural effusion, and nephrotoxicity. Serum IL-2 levels were detectable at the higher dose levels and were comparable to those observed in adult patients. Hematologic changes at the higher dose levels included rebound lymphocytosis occurring within 48 h of discontinuation of IL-2, eosinophilia, and decreased platelet counts. No objective responses to therapy were seen. We have identified a dose and schedule of administration for IL-2 in pediatric patients that can be given without intensive care unit support. Pediatric Phase II trials examining the anti-tumor activity of IL-2 given by this schedule are in progress. C1 NCI,PEDIAT BRANCH,BLDG 10,RM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. CARTER PRESIDENTIAL CTR,ATLANTA,GA. CHILDRENS CANC STUDY GRP,ARCADIA,CA. NCI,CLIN INVEST BRANCH,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. UNIV WISCONSIN,MADISON,WI 53706. CHILDRENS HOSP,NATL MED CTR,NATL MED CTR,WASHINGTON,DC 20010. SANDOZ PHARMACEUT CORP,E HANOVER,NJ. UNIV CHICAGO,CHICAGO,IL 60637. UNIV PADUA,I-35100 PADUA,ITALY. NR 72 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-8562 J9 AM J PEDIAT HEMATOL PD NOV PY 1992 VL 14 IS 4 BP 305 EP 311 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA JW443 UT WOS:A1992JW44300005 PM 1456395 ER PT J AU ABASSI, ZA TATE, J HUNSBERGER, S KLEIN, H TRACHEWSKY, D KEISER, HR AF ABASSI, ZA TATE, J HUNSBERGER, S KLEIN, H TRACHEWSKY, D KEISER, HR TI PHARMACOKINETICS OF ANF AND URODILATIN DURING CANF RECEPTOR BLOCKADE AND NEUTRAL ENDOPEPTIDASE INHIBITION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE URODILATIN; ATRIAL NATRIURETIC FACTOR; NEUTRAL ENDOPEPTIDASE INHIBITOR; CLEARANCE ATRIAL NATRIURETIC FACTOR RECEPTOR LIGAND; METABOLIC CLEARANCE RATE; VOLUME OF DISTRIBUTION; HALF-TIME; HYDROLYSIS OF URODILATIN; HYDROLYSIS OF ATRIAL NATRIURETIC FACTOR ID ATRIAL-NATRIURETIC-FACTOR; BLOOD-PRESSURE; HEART-FAILURE; CYCLIC-GMP; PEPTIDE; RATS; KIDNEY; MEMBRANES; METALLOENDOPEPTIDASE; ENKEPHALINASE AB Urodilatin is a new member of the family of natriuretic peptides. It is of renal origin. Previous reports indicate that urodilatin is natriuretic in lower doses than atrial natriuretic factor (ANF)-(99-126) and that it might be more effective than ANF in the treatment of cardiovascular edema. The present study was designed to compare the pharmacokinetics of the hydrolysis and clearance of I-125-labeled urodilatin and I-125-ANF. In control rats, the volume of distribution (V(ss)), metabolic clearance rate (MCR), and distribution half-life (distribution t1/2) of urodilatin in plasma were not significantly different from those of ANF. Infusion of clearance (c)ANF-(4-23), a specific ligand for receptors that clear ANF in excess amounts (i.e., a bolus injection of 100 mug/kg followed by a continuous infusion of 10 mug.kg-1-min-1), increased the amount of intact peptide in the plasma to the same extent for both urodilatin and ANF. In addition, cANF-(4-23) decreased the V(ss) and the MCR and increased the distribution t1/2 of both peptides to about the same degree. Prior treatment of rats with SQ-28,603, a specific neutral endopeptidase (NEP; EN 3.4.24.11) inhibitor, was without significant effect on the metabolic clearance of urodilatin, whereas it decreased the clearance of ANF by 65%. Furthermore, an infusion of SQ-28, 603 suppressed the appearance of the hydrolytic products of ANF in blood but not of urodilatin. Moreover, the inhibitor increased the total amount of ANF recovered in the kidneys to five times the control values, whereas it did not alter the renal uptake of urodilatin. These data demonstrate that urodilatin is removed from the circulation mainly by cANF receptors, whereas circulating ANF-(99-126) is cleared by both cANF receptors and NEP. This may contribute to the differences in the natriuretic potency of these two peptides, despite similar distribution t1/2, MCR, and V(ss). C1 US FDA,CTR DRUG EVALUAT,ROCKVILLE,MD 20857. US FDA,COLL RES STAFF,ROCKVILLE,MD 20857. RP ABASSI, ZA (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BLDG 10,RM 8C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 29 Z9 29 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 NOV PY 1992 VL 263 IS 5 BP E870 EP E876 PN 1 PG 7 WC Physiology SC Physiology GA JZ778 UT WOS:A1992JZ77800033 PM 1443119 ER PT J AU PETEN, EP GARCIAPEREZ, A TERADA, Y WOODROW, D MARTIN, BM STRIKER, GE STRIKER, LJ AF PETEN, EP GARCIAPEREZ, A TERADA, Y WOODROW, D MARTIN, BM STRIKER, GE STRIKER, LJ TI AGE-RELATED-CHANGES IN ALPHA-1-CHAIN AND ALPHA-2-CHAIN TYPE-IV COLLAGEN MESSENGER-RNAS IN ADULT-MOUSE GLOMERULI - COMPETITIVE PCR SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE COMPETITIVE POLYMERASE CHAIN REACTION; GENE REGULATION; GLOMERULUS; MICRODISSECTION ID POLYMERASE CHAIN-REACTION; BASEMENT-MEMBRANE; GROWTH-HORMONE; EXTRACELLULAR-MATRIX; TRANSGENIC MICE; GLOMERULOSCLEROSIS; EXPRESSION; LAMININ; KIDNEY; CELLS AB Studies of age-related changes in glomerular extracellular matrix (ECM) synthesis in normal mice have been hampered by the difficulty of isolating sufficient numbers of intact glomeruli and by the inability to quantify different mRNA species. The purpose of this study was to identify and quantitate the individual mRNAs coding for alpha1- and alpha2-chains of type IV collagen in isolated, single glomeruli of normal mice at different ages. These data on normal ECM synthesis were necessary for the understanding of glomerulosclerosis, a condition characterized by excess deposition of collagen. Pools of freshly microdissected adult mouse glomeruli were reverse transcribed in situ, and alpha1-IV and alpha2-IV collagen mRNAs were individually amplified by means of specific primers and the polymerase chain reaction (PCR), according to a previously published method. A competitive PCR assay, based on utilization of mutated cDNAs, allowed the reproducible, quantitative, and separate determination of the absolute amounts of both alpha1-IV and alpha2-IV mRNAs measured, as their respective cDNAs, in one-tenth of one glomerulus. The levels of alpha1-IV and alpha2-IV collagen mRNA were 208 +/- 36.0 x 10(-4) and 161.2 +/- 18.6 x 10(-4) amol/glomerulus in 5-wk-old mice. There were no significant age-related differences at 8, 12, and 24 wk. The mean levels over this period were 60.2 +/- 4.9 x 10(-4) for alpha1-IV collagen mRNA and 63.9 +/- 5.8 x 10(-4) amol/glomerulus for alpha2-IV collagen mRNA. Two of three 24-wk-old mice had mild glomerulosclerosis. The glomerular levels of both mRNAs were elevated 1.8-fold in these mice, compared with normal 8- to 24-wk-old animals. C1 NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. UNIV LONDON,CHARING CROSS & WESTMINSTER MED SCH,DEPT HISTOPATHOL,LONDON W6 8RF,ENGLAND. NR 31 TC 74 Z9 74 U1 0 U2 3 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 NOV PY 1992 VL 263 IS 5 BP F951 EP F957 PN 2 PG 7 WC Physiology SC Physiology GA JZ779 UT WOS:A1992JZ77900095 PM 1443183 ER PT J AU SATO, S AF SATO, S TI RAT-KIDNEY ALDOSE REDUCTASE AND ALDEHYDE REDUCTASE AND POLYOL PRODUCTION IN RAT-KIDNEY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GALACTITOL; SORBITOL; ALDOSE REDUCTASE INHIBITORS ID ORAL SORBINIL; INHIBITORS; PREVENTION; COMPLICATIONS; DEHYDROGENASE; LOCALIZATION; PROTEINURIA; SORBITOL; BRAIN AB Mounting evidence indicates that aldose reductase catalyzed reduction of excess glucose to sorbitol initiates the onset of certain diabetic complications. However, the kidney contains a large amount of aldehyde reductase, another NADPH-dependent reductase. The study was designed to assess the importance of these reductases to sugar alcohol (polyol) production in the kidney. To study the ability to reduce aldoses to polyols, both aldose and aldehyde reductases were purified from rat kidneys. Incubation studies with purified enzymes clearly demonstrated the polyol formation by both enzymes. Galactose feeding induced polyol accumulation in both medulla and cortex of the rat kidney. Al 1576, a potent inhibitor of both enzymes, reduced this polyol accumulation in both cortex and medulla, while the selective inhibitors Ponalrestat or FK 366 resulted in greater inhibition in medulla than cortex. These results suggest that kidney polyols may be generated by both aldose and aldehyde reductases and that aldehyde reductase contributes to polyol production in the kidney cortex, the predominant site of diabetes-linked kidney lesions. RP SATO, S (reprint author), NEI,BLDG 10,RM 10B09,BETHESDA,MD 20892, USA. NR 34 TC 31 Z9 33 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 NOV PY 1992 VL 263 IS 5 BP F799 EP F805 PN 2 PG 7 WC Physiology SC Physiology GA JZ779 UT WOS:A1992JZ77900075 PM 1443170 ER PT J AU ANDREASON, PJ ALTEMUS, M ZAMETKIN, AJ KING, AC LUCINIO, J COHEN, RM AF ANDREASON, PJ ALTEMUS, M ZAMETKIN, AJ KING, AC LUCINIO, J COHEN, RM TI REGIONAL CEREBRAL GLUCOSE-METABOLISM IN BULIMIA-NERVOSA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 144TH ANNUAL MEETING OF THE AMERICAN PSYCHIATRIC ASSOC CY MAY 11-16, 1991 CL NEW ORLEANS, LA SP AMER PSYCHIAT ASSOC ID POSITRON EMISSION TOMOGRAPHY; OBSESSIVE-COMPULSIVE DISORDER; DEPRESSION; CORTEX; RATES AB Objective: The authors' purpose in this study was to further delineate the character of cerebral metabolism in bulimia nervosa and to determine if functional links could be made between regional cerebral metabolism and the symptoms of depression, obsessive-compulsive disorder, and bulimia nervosa. Method, Regional cerebral glucose metabolism was measured by using positron emission tomography in 11 inpatients with bulimia nervosa and 18 normal comparison subjects matched in sex (all were women), age, and educational level. The bulimic patients were also tested for symptoms of major depression and obsessive-compulsive disorder. Results: The patients with bulimia showed a correlation between lower left anterolateral prefrontal regional cerebral glucose metabolism and greater depressive symptoms. However, the orbitofrontal regional cerebral glucose metabolism of patients with bulimia was not greater than that of comparison subjects, nor was higher orbitofrontal metabolism correlated with greater obsessive-compulsive disorder symptoms. Conclusions: These findings lead to the conclusion that left anterior lateral prefrontal cortex hypometabolism varies with the depressive symptoms observed in bulimia but that temporal lobe hypermetabolism and asymmetries appear to be independent of the mood state. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 21 TC 42 Z9 42 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1992 VL 149 IS 11 BP 1506 EP 1513 PG 8 WC Psychiatry SC Psychiatry GA JV476 UT WOS:A1992JV47600007 PM 1415817 ER PT J AU BIGGAR, RJ MELBYE, M AF BIGGAR, RJ MELBYE, M TI RESPONSES TO ANONYMOUS QUESTIONNAIRES CONCERNING SEXUAL-BEHAVIOR - A METHOD TO EXAMINE POTENTIAL BIASES SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HIV-INFECTION; MEN; TRANSMISSION; POPULATION; PATTERNS; RISK; AIDS AB Objectives. Low response rates to voluntary surveys raise questions about how representative the responses are. We compared the behavior and attitudes of responders, willing and reluctant, and nonresponders to anonymous questionnaires about behaviors that might expose participants to the human immunodeficiency virus (HIV). Methods. Questionnaires were sent to 1080 Danish adults 18 through 59 years including explicit questions about sexual acts and illegal drug use. Identical questionnaires were sent to 3600 other Danes, similarly chosen; packets sent to these persons included cards to be returned separately informing us that they had responded. Questionnaires were sent twice more to nonresponders, who, if they then responded, were considered reluctant responders. One hundred nonresponders were telephoned and asked why they had refused to respond. Results. Enclosing return cards did not affect initial response rate, but prompting boosted replies from 52% to 73%. However, behaviors were generally similar among initial and reluctant responders. One third of nonresponders agreed to respond if we wished (total potential response: 82%). In general, the reasons for nonresponse did not suggest that the lifestyles of nonresponders placed them at risk for HIV infection. Conclusions. This method provides a simple, inexpensive approach to improving response rates and learning about the biases of reluctant responders and nonresponders. C1 DANISH CANC REGISTRY,AIDS RES,COPENHAGEN,DENMARK. NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892. STATE SERUM INST,DEPT EPIDEMIOL,COPENHAGEN,DENMARK. NR 22 TC 49 Z9 48 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 NOV PY 1992 VL 82 IS 11 BP 1506 EP 1512 DI 10.2105/AJPH.82.11.1506 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JW902 UT WOS:A1992JW90200012 PM 1443301 ER PT J AU BROWNSON, RC ALAVANJA, MCR HOCK, ET LOY, TS AF BROWNSON, RC ALAVANJA, MCR HOCK, ET LOY, TS TI PASSIVE SMOKING AND LUNG-CANCER IN NONSMOKING WOMEN SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CHINESE-WOMEN; TOBACCO-SMOKE; UNITED-STATES; RISK-FACTORS; EXPOSURE; MORTALITY; LIFETIME; TRENDS AB Objectives. The causes of lung cancer among nonsmokers are not clearly understood. To further evaluate the relation between passive smoke exposure and lung cancer in nonsmoking women, we conducted a population-based, case control study. Methods. Case patients (n = 618), identified through the Missouri Cancer Registry for the period 1986 through 1991, included 432 life-time nonsmokers and 186 ex-smokers who had stopped at least 15 years before diagnosis or who had smoked for less than 1 pack-year. Control subjects (n = 1402) were selected from driver's license and Medicare files. Results. No increased risk of lung cancer was associated with childhood passive smoke exposure. Adulthood analyses showed an increased lung cancer risk for lifetime nonsmokers with exposure of more than 40 pack-years from all house-hold members (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0, 1.8) or from spouses only (OR = 1.3; 95% CI = 1.0, 1.7). When the time-weighted product of pack-years and average hours exposed per day was considered, a 30% excess risk was shown at the highest quartile of exposure among lifetime nonsmokers. Conclusions. Ours and other recent studies suggest a small but consistent increased risk of lung cancer from passive smoker. Comprehensive actions to limit smoking in public places and worksites are well-advised. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. UNIV MISSOURI,MED CTR,SCH MED,DEPT PATHOL,COLUMBIA,MO 65201. RP BROWNSON, RC (reprint author), MISSOURI DEPT HLTH,DIV CHRON DIS PREVENT & HLTH PROMOT,201 BUSINESS LOOP 70 W,COLUMBIA,MO 65203, USA. FU NCI NIH HHS [N01-CP7-1096-01, N01-CP7-1096-02] NR 44 TC 125 Z9 125 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 NOV PY 1992 VL 82 IS 11 BP 1525 EP 1530 DI 10.2105/AJPH.82.11.1525 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JW902 UT WOS:A1992JW90200015 PM 1443304 ER PT J AU HOOVER, DR SAAH, A BACELLAR, H MURPHY, R VISSCHER, B METZ, S ANDERSON, R KASLOW, RA AF HOOVER, DR SAAH, A BACELLAR, H MURPHY, R VISSCHER, B METZ, S ANDERSON, R KASLOW, RA TI THE PROGRESSION OF UNTREATED HIV-1 INFECTION PRIOR TO AIDS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; COHORT; ZIDOVUDINE; AZT AB Using a case-control study of untreated men, we investigated the physical, mental, and economic effects of human immunodeficiency virus (HIV-1) infection prior to the diagnosis of acquired immunodeficiency syndrome (AIDS). Beginning 2 to 2.5 years prior to AIDS, case subjects reported more of 12 HIV-1 related symptoms and during the year prior to AIDS, at least 30.6 extra days of these symptoms than did control subjects. Within the 6 months preceding AIDS, case subjects' unemployment rose to 9% (P less-than-or-equal-to .05) and depression to 34.2% (P less-than-or-equal-to .001). At 6 to 12 months and within 6 months before AIDS, 17.1% and 31.5%, respectively, were anemic, while 37.7% and 64.7% and CD4+ counts less than 200 x 10(6)/L. Diagnosing AIDS at CD4+ counts less than 200 x 10(6)/L could significantly reduce pre-AIDs morbidity. Other implications of these findings are discussed. C1 UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15260. NIAID,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,DIV INFECT DIS,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. RP HOOVER, DR (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,624N BROADWAY,ROOM 784,BALTIMORE,MD 21205, USA. OI Murphy, Robert/0000-0003-3936-2052 FU NIAID NIH HHS [AI-72632, AI-72634, AI-72631] NR 14 TC 19 Z9 19 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 NOV PY 1992 VL 82 IS 11 BP 1538 EP 1541 DI 10.2105/AJPH.82.11.1538 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JW902 UT WOS:A1992JW90200019 PM 1359801 ER PT J AU AGUIAR, JC ALBRECHT, GR CEGIELSKI, P GREENWOOD, BM JENSEN, JB LALLINGER, G MARTINEZ, A MCGREGOR, IA MINJAS, JN NEEQUAYE, J PATARROYO, ME SHERWOOD, JA HOWARD, RJ AF AGUIAR, JC ALBRECHT, GR CEGIELSKI, P GREENWOOD, BM JENSEN, JB LALLINGER, G MARTINEZ, A MCGREGOR, IA MINJAS, JN NEEQUAYE, J PATARROYO, ME SHERWOOD, JA HOWARD, RJ TI AGGLUTINATION OF PLASMODIUM-FALCIPARUM-INFECTED ERYTHROCYTES FROM EAST AND WEST AFRICAN ISOLATES BY HUMAN SERA FROM DISTANT GEOGRAPHIC REGIONS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PAPUA-NEW-GUINEA; ANTIGENS; ANTIBODIES; PARASITES; ASSAYS AB Plasmodium falciparum-infected erythrocytes (PfE) were collected from acutely infected children in The Gambia and Tanzania and cultured for more than 30 hr until the parasites were mature trophozoites. Sera collected from these countries, other African countries, Asia, and South America were used in the PfE microagglutination test to determine whether PfE from East and West Africa share surface antigens. From the patterns of agglutination reactivity, we identified extensive antigenic diversity in surface antigens, but obtained no evidence for greater differences between isolates from East or West Africa and those within one region. The majority of sera from immune adults from The Gambia, Tanzania, Sudan, Nigeria, or Ghana were pan-agglutinating, and agglutinated all PfE isolates from The Gambia and Tanzania. Some sera from immune adults of Irian Jaya also agglutinated each of the seven African isolates, while others agglutinated many but not all of the isolates, similar to sera from immune adults of Flores, Indonesia. In contrast, sera from nonimmune adults from Colombia agglutinated few of the African isolates. It was remarkable, however, that sera from nonimmune Colombians agglutinated any African isolates. Our results are consistent with the following conclusions: some PfE surface antigen(s) are very diverse; this diversity is a feature of the parasite worldwide; the repertoire of isolate-specific surface antigens, although large, includes antigens that are either identical or antigenically cross-reactive in geographically very distant parasite populations; and African adults have pan-agglutinating antibodies that may contribute to protective immunity. Such pan-agglutinating antibodies could reflect the accumulation of a large repertoire of isolate-specific antibodies. The contribution of antibody against any shared PfE surface antigen to the pan-agglutinating reactivities is unknown and awaits development of the appropriate reagents. C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,INFECT DIS LAB,PALO ALTO,CA. MED RES LABS,FAJARA,SENEGAMBIA. BRIGHAM YOUNG UNIV,DEPT MICROBIOL,PROVO,UT 84602. HOSP SAN JUAN DIOS,INST INMUNOL,BOGOTA,COLOMBIA. UNIV LIVERPOOL,LIVERPOOL SCH TROP MED,DEPT TROP MED & INFECT DIS,LIVERPOOL L3 5QA,ENGLAND. UNIV GHANA,SCH MED,DEPT CHILD HLTH,ACCRA,GHANA. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. MUHIMBILI MED RES CTR,DAR ES SALAAM,TANZANIA. NR 8 TC 54 Z9 54 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 1992 VL 47 IS 5 BP 621 EP 632 PG 12 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA KA498 UT WOS:A1992KA49800012 PM 1449203 ER PT J AU WILLIAMSON, KC DUFFY, PE KASLOW, DC AF WILLIAMSON, KC DUFFY, PE KASLOW, DC TI IMMUNOAFFINITY CHROMATOGRAPHY USING ELECTROELUTION SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID TRANSMISSION-BLOCKING ANTIBODIES; PLASMODIUM-GALLINACEUM; MONOCLONAL-ANTIBODIES; SURFACE PROTEIN; MALARIA; TARGET; ANTIGENS; IMMUNITY C1 WALTER REED ARMY INST RES,DEPT MED,WASHINGTON,DC 20307. RP WILLIAMSON, KC (reprint author), NIAID,MALARIA RES LAB,BETHESDA,MD 20892, USA. NR 13 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV PY 1992 VL 206 IS 2 BP 359 EP 362 DI 10.1016/0003-2697(92)90378-K PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JW129 UT WOS:A1992JW12900023 PM 1443606 ER PT J AU HEEGAARD, NHH ROBEY, FA AF HEEGAARD, NHH ROBEY, FA TI USE OF CAPILLARY ZONE ELECTROPHORESIS TO EVALUATE THE BINDING OF ANIONIC CARBOHYDRATES TO SYNTHETIC PEPTIDES DERIVED FROM HUMAN SERUM AMYLOID-P COMPONENT SO ANALYTICAL CHEMISTRY LA English DT Article ID AFFINITY; PROTEINS AB Capillary zone electrophoresis was used to study interactions between anionic carbohydrates and synthetic peptides derived from the heparin-binding region of human serum amyloid P component. The method involves quantitation of unbound peptides after a charge-dependent electrophoretic separation of the peptide-carbohydrate mixture. The concentrations of free peptide were determined by extrapolating the obtained peak areas of the peptide in the presence of ligand to a standard curve. Dissociation constants in the 10(-5) M range were determined, and differences in binding affinity of various peptide modifications were illustrated. The assay requires minute amounts of material (sample volume is 7 - 15 nL), and as long as the reactants are soluble at the chosen conditions, no modifications or special characteristics of the interacting molecules are needed for their identification. It should be possible to use electrophoretic separation in capillaries to evaluate the binding of peptides to any ligand as long as the differences in charge/mass ratio between free and complexed peptide are of a sufficient magnitude as in the peptide-heparin binding demonstrated here RP HEEGAARD, NHH (reprint author), NIDR,PEPTIDE & IMMUNOCHEM UNIT,CELLULAR DEV & ONCOL LAB,BLDG 30,BETHESDA,MD 20892, USA. NR 18 TC 105 Z9 110 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 1992 VL 64 IS 21 BP 2479 EP 2482 DI 10.1021/ac00045a004 PG 4 WC Chemistry, Analytical SC Chemistry GA JV783 UT WOS:A1992JV78300005 PM 1443623 ER PT J AU DETERDING, LJ DIX, K BURKA, LT TOMER, KB AF DETERDING, LJ DIX, K BURKA, LT TOMER, KB TI ONLINE COUPLING OF INVIVO MICRODIALYSIS WITH TANDEM MASS-SPECTROMETRY SO ANALYTICAL CHEMISTRY LA English DT Article ID FAST ATOM BOMBARDMENT; TRIS(2-CHLOROETHYL) PHOSPHATE; LIQUID-CHROMATOGRAPHY; PROBES; RATS AB The capability of interfacing in vivo microdialysis with mass spectrometry has been demonstrated. The goal of this research was to demonstrate the feasibility of real-time analysis in biological systems using microdialysis in combination with tandem mass spectrometry (MS/MS). Microdialysis sampling was accomplished by surgically implanting a small microdialysis probe into a tissue or area of interest. Molecules diffuse through the membrane of the microdialysis probe due to concentration differences. These molecules are collected in a sample loop and analyzed by tandem mass spectrometry. Sequential injections can be made in as little as 2 min. This capability is advantageous in the study of molecules with very rapid elimination rates. Tris(2-chloroethyl) phosphate (TRCP) was used as a model compound in the development of this analytical technique. As an example of an application of the microdialysis/MS/MS technique, plasma concentration vs time curves were obtained and compared with the plasma concentration profiles obtained using conventional studies. For the microdialysis/MS/MS studies, the average slope from three animals was -0.086 min-1. In comparison, the average slope from four animals from the conventional studies was -0.035 min-1. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. NIEHS,EXPTL TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 23 TC 40 Z9 41 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 1992 VL 64 IS 21 BP 2636 EP 2641 DI 10.1021/ac00045a029 PG 6 WC Chemistry, Analytical SC Chemistry GA JV783 UT WOS:A1992JV78300030 PM 1443626 ER PT J AU OEHNINGER, S FRANKEN, D ALEXANDER, N HODGEN, GD AF OEHNINGER, S FRANKEN, D ALEXANDER, N HODGEN, GD TI HEMIZONA ASSAY AND ITS IMPACT ON THE IDENTIFICATION AND TREATMENT OF HUMAN SPERM DYSFUNCTIONS SO ANDROLOGIA LA English DT Review DE HEMIZONA ASSAY; ZONA-PELLUCIDA; GAMETE INTERACTION; SPERM DYSFUNCTION; HUMAN ID HUMAN ZONA-PELLUCIDA; HUMAN FOLLICULAR-FLUID; MALE-FACTOR INFERTILITY; STORED HUMAN OOCYTES; HUMAN-SPERMATOZOA; INVITRO FERTILIZATION; ACROSOME REACTION; IMMUNOLOGICAL INFERTILITY; HYPERACTIVATED MOTILITY; ANTISPERM ANTIBODIES AB The HZA, a functional test for human gamete interaction, has become a useful and valuable experimental tool for physiological and cellular analysis of the early events leading to fertilization. The analysis of the conventional semen parameters with emphasis on sperm morphology (as judged by strict criteria) and motion characteristics (evaluated by computer assisted analysis) constitutes the first obligatory step for a critical evaluation of male-factor patients. Patients in whom fertilization disorders are suspected should be evaluated through bioassays of sperm function of established accuracy. The HZA, a bioassay of sperm-zona binding capacity is here proven to be highly predictive of IVF outcome. Ultimately, our increasing knowledge of sperm biology and dysfunction will provide a basis for a better diagnosis (membrane receptor defects and metabolic/biochemical abnormalities?) as well as better therapeutic interventions in patients with sperm disorders. It seems likely that the HZA may be eventually replaced by a standardized test kit in which recombinant human DNA-derived zona receptors mimic the natural function of the hemizonae currently used. This ZP3 reagent may also be a useful antigen for contraceptive development. The HZA therefore constitutes a useful adjuvant in the armentarium for the diagnosis and therapy of male-factor patients. C1 UNIV STELLENBOSCH,TYGERBERG HOSP,DEPT OBSTET & GYNECOL,REPROD BIOL UNIT,TYGERBERG 7505,SOUTH AFRICA. NICHHD,CTR POPULAT RES,BETHESDA,MD 20892. RP OEHNINGER, S (reprint author), EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,DEPT OBSTET & GYNECOL,601 COLLEY AVE,NORFOLK,VA 23507, USA. NR 88 TC 38 Z9 38 U1 0 U2 1 PU BLACKWELL WISSENSCHAFTS-VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0303-4569 J9 ANDROLOGIA JI Andrologia PD NOV-DEC PY 1992 VL 24 IS 6 BP 307 EP 321 PG 15 WC Andrology SC Endocrinology & Metabolism GA JX621 UT WOS:A1992JX62100003 PM 1443672 ER PT J AU ANDERSON, DW ELLENBERG, JH LEVENTHAL, CM REINGOLD, SC RODRIGUEZ, M SILBERBERG, DH AF ANDERSON, DW ELLENBERG, JH LEVENTHAL, CM REINGOLD, SC RODRIGUEZ, M SILBERBERG, DH TI PREVALENCE OF MULTIPLE-SCLEROSIS - REPLY SO ANNALS OF NEUROLOGY LA English DT Letter ID EPIDEMIOLOGY C1 NATL MULTIPLE SCLEROSIS SOC,MED PROGRAM,NEW YORK,NY. NATL MULTIPLE SCLEROSIS SOC,RES PROGRAM,NEW YORK,NY. MAYO CLIN & MAYO FDN,DEPT NEUROL,ROCHESTER,MN 55905. UNIV PENN,MED CTR,DEPT NEUROL,PHILADELPHIA,PA 19104. NATL INST NEUROL DISORDERS & STROKE,DIV DEMYELINATING ATROP & DEMENTING DISORDERS,BETHESDA,MD. RP ANDERSON, DW (reprint author), NATL INST NEUROL DISORDERS & STROKE,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1992 VL 32 IS 5 BP 718 EP 719 DI 10.1002/ana.410320523 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JW891 UT WOS:A1992JW89100022 ER PT J AU HENDRIKS, HR PLOWMAN, J BERGER, DP PAULL, KD FIEBIG, HH FODSTAD, O DREEFVANDERMEULEN, HC HENRAR, REC PINEDO, HM SCHWARTSMANN, G AF HENDRIKS, HR PLOWMAN, J BERGER, DP PAULL, KD FIEBIG, HH FODSTAD, O DREEFVANDERMEULEN, HC HENRAR, REC PINEDO, HM SCHWARTSMANN, G TI PRECLINICAL ANTITUMOR-ACTIVITY AND ANIMAL TOXICOLOGY STUDIES OF RHIZOXIN, A NOVEL TUBULIN-INTERACTING AGENT SO ANNALS OF ONCOLOGY LA English DT Article DE RHIZOXIN; TUBULIN BINDER; ANTITUMOR ACTIVITY; NCI INVITRO SCREEN; VINCA ALKALOID SENSITIVES RESISTANTS; ANIMAL TOXICOLOGY ID MACROCYCLIC LACTONE ANTIBIOTICS; HUMAN-TUMOR XENOGRAFTS; PHASE-II; CROSS-RESISTANCE; CELL-LINES; MAYTANSINE; SARCOMAS; ASSAY; BINDING; INVIVO AB Rhizoxin is a 16-membered antifungal macrocyclic lactone isolated from the plant pathogenic fungus Rhizopus chinensis. The compound binds to tubulin, preventing microtubule formation, and inhibiting mitosis. It possesses antitumour activity in vivo against various preclinical murine models, both leukaemias and solid tumours model, as well as in vincristine- and doxorubicin-resistant leukaemia lines. In the present study, cytotoxic activity was observed in human tumour cell lines in vitro at very low concentrations (+/- 10(-10) M) particularly against melanoma, colon, renal, non-small cell and small cell lung cancer. In vivo antitumour activity was demonstrated in murine P388 and L1210 murine leukaemias, solid tumour models B16 melanoma and M5076 sarcoma, and in 5 out of 9 human solid tumour xenografts: LOX melanoma, MX-1 breast cancer. non-small cell lung cancer A549, and small cell lung cancers LXFS 605 and LXFS 650. The absence of cross-resistance to vinca alkaloids was confirmed in vivo against the vincristine-resistant P388 leukaemia subline and the vincristine-resistant human small cell lung cancer LXFS 650. In addition, the antitumour activity of rhizoxin was improved by prolonged or repeated drug administration indicating a schedule dependency. In animal toxicology studies, transient changes in erythrocyte and leukocyte numbers, local phlebitis, diarrhea, and spermatogenic arrest were observed. The LD10 value of rhizoxin after a single intravenous injection was 2.8 mg/kg (8.4 mg/m2). One-tenth ot the mouse equivalent LD10 (0.84 mg/m2), the starting dose for clinical phase I studies, was considered to be safe in rats. The antitumour activity of rhizoxin, its unique interactions with tubulin and the absence of non-manageable toxic effects in the animal toxicological studies have led to rhizoxin's selection for clinical trials. A phase I clinical trial has been completed showing leukopenia, mucositis and diarrhea to be the dose-limiting toxicities. In some cases phlebitis was observed. These toxicities were predicted from the animal toxicological studies. In addition, rhizoxin caused minor responses in three heavily pretreated patients with recurrent breast cancer. Phase II clinical trials will start soon within the framework of the EORTC and CRC. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. UNIV FREIBURG,DEPT INTERNAL MED,W-7800 FREIBURG,GERMANY. NORWEGIAN RADIUM HOSP,DEPT TUMOR BIOL,OSLO 3,NORWAY. TNO,CIVO INST,ZEIST,NETHERLANDS. RP HENDRIKS, HR (reprint author), FREE UNIV AMSTERDAM HOSP,EORTC NEW DRUG DEV OFF,DE BOELELAAN 1117,1081 HV AMSTERDAM,NETHERLANDS. RI Schwartsmann, Gilberto/G-4256-2016; OI Schwartsmann, Gilberto/0000-0002-7850-1644; Hendriks, Hans/0000-0003-1109-4615 NR 34 TC 29 Z9 30 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 1992 VL 3 IS 9 BP 755 EP 763 PG 9 WC Oncology SC Oncology GA JW882 UT WOS:A1992JW88200022 PM 1450065 ER PT J AU CALABRO, A HASCALL, VC CATERSON, B AF CALABRO, A HASCALL, VC CATERSON, B TI MONOCLONAL-ANTIBODIES DIRECTED AGAINST EPITOPES WITHIN THE CORE PROTEIN-STRUCTURE OF THE LARGE AGGREGATING PROTEOGLYCAN (AGGRECAN) FROM THE SWARM RAT CHONDROSARCOMA SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID CARTILAGE PROTEOGLYCAN; KERATAN SULFATE; LINK PROTEIN; HYALURONIC-ACID; G2 DOMAIN; SEQUENCE; PEPTIDES; REGION; IDENTIFICATION; DETERMINANTS C1 UNIV N CAROLINA,DIV ORTHOPED SURG,CHAPEL HILL,NC 27599. RP CALABRO, A (reprint author), NIDR,BONE RES BRANCH,BETHESDA,MD 20892, USA. RI Caterson, Bruce/A-8085-2010 FU NIAMS NIH HHS [AR 32666] NR 43 TC 35 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 1 PY 1992 VL 298 IS 2 BP 349 EP 360 DI 10.1016/0003-9861(92)90421-R PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JU070 UT WOS:A1992JU07000006 PM 1384430 ER PT J AU TAKEUCHI, Y YANAGISHITA, M HASCALL, VC AF TAKEUCHI, Y YANAGISHITA, M HASCALL, VC TI EFFECTS OF MGCL2 ON THE RELEASE AND RECYCLING OF HEPARAN-SULFATE PROTEOGLYCANS IN A RAT PARATHYROID CELL-LINE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID PROTEIN KINASE-C; EXTRACELLULAR CALCIUM; INOSITOL PHOSPHATES; SYNAPTIC VESICLES; CORE PROTEOGLYCAN; DIVALENT-CATIONS; SECRETION; CA-2+; ELECTROMOTONEURONES; TRANSPORT C1 NIDR,BONE RES PROGRAM,BETHESDA,MD 20892. NR 29 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD NOV 1 PY 1992 VL 298 IS 2 BP 371 EP 379 DI 10.1016/0003-9861(92)90424-U PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JU070 UT WOS:A1992JU07000009 PM 1416969 ER PT J AU ROSS, V ROMAN, L RUSHIN, JM COBB, MW FRIEDMAN, KJ AF ROSS, V ROMAN, L RUSHIN, JM COBB, MW FRIEDMAN, KJ TI XANTHOMATIZED ATYPICAL T-CELLS IN A PATIENT WITH MYCOSIS-FUNGOIDES AND HYPERLIPIDEMIA SO ARCHIVES OF DERMATOLOGY LA English DT Article ID HEMOPHAGOCYTIC SYNDROME; SUBCUTANEOUS TISSUE; LYMPHOCYTES-T; ATHEROGENESIS AB Background.-Lipoprotein-T-cell interactions are being reported with increasing frequency, and there is evidence that lipoproteins play a role in immunoregulation. We describe a patient with mycosis fungoides and hyperlipidemia who developed xanthomatization in one preexisting plaque. The case is unique in that some of the lipidized cells were atypical T cells. In previously reported cases of mycosis fungoides with dystrophic xanthomatosis, the lipid-containing cells have been identified only as histiocytes. Observations.-Immunopathologic feautures, electron microscopy, and lipid stains of the xanthomatized plaque demonstrated that some of the lipid-laden cells were atypical T cells. Conclusions.-In mycosis fungoides, malignant T cells may be intimately involved in processing of tissue lipids. We suggest that low-density lipoprotein receptors on activated T cells facilitated the cytoplasmic lipidization in this case. C1 USN, NATL MED CTR, DEPT LAB MED, BETHESDA, MD 20814 USA. NIH, HEMATOPATHOL SECT, PATHOL LAB, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT DERMATOL, BETHESDA, MD 20814 USA. RP ROSS, V (reprint author), USN, NATL MED CTR, DEPT DERMATOL, BETHESDA, MD 20814 USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-987X EI 1538-3652 J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 1992 VL 128 IS 11 BP 1499 EP 1502 PG 4 WC Dermatology SC Dermatology GA JX149 UT WOS:A1992JX14900009 ER PT J AU GOLDMAN, LR GOMEZ, M GREENFIELD, S HALL, L HULKA, BS KAYE, WE LYBARGER, JA MCKENZIE, DH MURPHY, RS WELLINGTON, DG WOODRUFF, T AF GOLDMAN, LR GOMEZ, M GREENFIELD, S HALL, L HULKA, BS KAYE, WE LYBARGER, JA MCKENZIE, DH MURPHY, RS WELLINGTON, DG WOODRUFF, T TI USE OF EXPOSURE DATABASES FOR STATUS AND TRENDS ANALYSIS SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID AIR-POLLUTION AB Exposure databases are useful for monitoring status and trends in environmental health. However, other supporting data are usually needed to infer human exposure or internal dose. Program planning and evaluation, environmental health surveillance, epidemiologic research, and contributions to international efforts are four major purposes for monitoring environmental exposure status and trends. Although databases play an important role in monitoring human exposure, certain methodological problems need to be overcome. The work group developed six criteria for meeting information needs for human exposure assessment. Areas that need attention are (1) specification of location, (2) specification of facility and chemical identifiers, (3) documentation of special populations at risk, (4) provision of early warning of new problems, (5) monitoring changes over time, and (6) enhancement of documentation. We tested these criteria by examining six available databases that might be used for monitoring exposure to contaminants in drinking water. Available data fell short of information needs. We drew four conclusions and offered several recommendations for each. First, available data systems lack adequate measures of human exposure. Second, data for monitoring exposures for many important population subgroups and environmental settings are inadequate. Third, an ''early warning'' system that monitors human exposures is needed. Fourth, designers of data-collection systems should consider the needs of users who monitor status and trends of human exposure. C1 NCI,OCCUPAT STUDIES SECT,ROCKVILLE,MD. SYST APPLICAT INC,SAN RAFAEL,CA 94903. US EPA,OFF POLLUT PREVENT & TOX,WASHINGTON,DC 20460. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. AGCY TOX SUBST & DIS REGISTRY,DIV HLTH STUDIES,EPIDEMIOL & SURVEILLANCE BRANCH,ATLANTA,GA. US EPA,CORVALLIS ENVIRONM RES LAB,CORVALLIS,OR 97330. NATL CTR HLTH STAT,CTR DIS CONTROL,DIV HLTH EXAMINAT STAT,HYATTSVILLE,MD 20782. US EPA,STAT POLICY BRANCH,WASHINGTON,DC 20460. UNIV CALIF SAN FRANCISCO,INST HLTH POLICY STUDIES,SAN FRANCISCO,CA 94143. RP GOLDMAN, LR (reprint author), CALIF DEPT HLTH SERV,DIV ENVIRONM & OCCUPAT DIS CONTROL,5900 HOLLIS ST,SUITE E,EMERYVILLE,CA 94608, USA. RI Goldman, Lynn/D-5372-2012 NR 13 TC 15 Z9 15 U1 0 U2 1 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD NOV-DEC PY 1992 VL 47 IS 6 BP 430 EP 438 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA KH566 UT WOS:A1992KH56600004 PM 1485806 ER PT J AU BREWERTON, TD MUELLER, EA LESEM, MD BRANDT, HA QUEARRY, B GEORGE, DT MURPHY, DL JIMERSON, DC AF BREWERTON, TD MUELLER, EA LESEM, MD BRANDT, HA QUEARRY, B GEORGE, DT MURPHY, DL JIMERSON, DC TI NEUROENDOCRINE RESPONSES TO M-CHLOROPHENYLPIPERAZINE AND L-TRYPTOPHAN IN BULIMIA SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID TRITIATED IMIPRAMINE BINDING; PLATELET IMIPRAMINE BINDING; NEURO-ENDOCRINE RESPONSES; ANTI-DEPRESSANT TREATMENT; PLASMA-CORTISOL LEVELS; DORSAL RAPHE NUCLEUS; DOUBLE-BLIND; META-CHLOROPHENYLPIPERAZINE; ANOREXIA-NERVOSA; PSYCHIATRIC-DISORDERS AB Preclinical and clinical evidence supports a theory of serotonin (5-hydroxytryptamine [5-HT]) dysregulation in bulimia. We therefore studied the prolactin (PRL) and cortisol responses following challenges with the postsynaptic 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg orally, the 5-HT precursor L-tryptophan, 100 mg/kg intravenously, and placebo in a group of 28 normal weight bulimic patients and 16 healthy controls. Patients with bulimia, regardless of the presence of major depression, had significantly blunted PRL responses following m-CPP administration compared with those in controls. In contrast, only bulimic patients with concurrent major depression had significantly blunted PRL responses following L-tryptophan administration compared with those in nondepressed bulimic patients and controls. Cortisol responses following m-CPP were not significantly different for bulimic patients vs controls, although there was a trend toward blunted cortisol responses following L-tryptophan administration in the depressed bulimic patients. These differences in neuroendocrine responses were not related to differences in age, percent of average body weight, medications, time of day, peak plasma drug levels, or baseline estradiol levels. Seasonal variations in PRL responses to both agents were identified, although covariation for season did not alter the group differences. The PRL responses following m-CPP administration were inversely correlated to baseline cortisol levels in the bulimic patients, but not in the controls, suggesting a dampening effect by hypothalamic-pituitary-adrenal axis dysfunction on postsynaptic 5-HT receptor sensitivity. The reasons for the differing hormonal responses to these two serotonergic agents may relate to differential involvement of presynaptic and postsynaptic mechanisms, 5-HT receptor subtypes, and anatomical loci of action. The blunted PRL responses to m-CPP administration suggest that postsynaptic 5-HT receptor sensitivity is altered in bulimia nervosa, and that similar alterations in 5-HT receptors at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms. C1 NIMH,CLIN SCI LAB,BIOMED PSYCHIAT SECT,BETHESDA,MD 20892. NR 126 TC 97 Z9 97 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 1992 VL 49 IS 11 BP 852 EP 861 PG 10 WC Psychiatry SC Psychiatry GA JX303 UT WOS:A1992JX30300002 PM 1444722 ER PT J AU LEMON, SJ SIENKO, DG ALGUIRE, PC AF LEMON, SJ SIENKO, DG ALGUIRE, PC TI PHYSICIANS ATTITUDES TOWARD MANDATORY WORKPLACE URINE DRUG-TESTING SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MEDICAL-STUDENTS; SUBSTANCE USE AB Background.-Workplace drug testing programs are being increasingly implemented in both the public and private sectors, and health care workers are unlikely to be excluded from such testing. Methods.-A survey of attending physicians' attitudes toward mandatory hospital-based urine drug testing was undertaken in a medium-sized, midwestern county. Results.-Seventy-four percent (272/368) of the sample responded. Seventy-two percent of the subjects believed physician drug use to be a minor or nonexistent problem, 38% lacked confidence in the testing procedure, and 60% believed that testing infringed on the physician's right to privacy; yet 87% would,submit to testing if required by a hospital. Forty-five percent of respondents agreed with the policy of mandatory testing for physicians with hospital privileges, 34% disagreed, and 21% were uncertain. Respondents were more supportive of mandatory testing of other health care and non-health care occupations than for themselves. Support for testing was greatest for illicit drugs. If implemented, physicians preferred mandatory testing to be performed by hospital medical staff independent of hospital administration. Conclusions.-Further education and discussion within the physician community appears to be necessary before widespread mandatory workplace urine drug testing of physicians is implemented. C1 MICHIGAN STATE UNIV, DEPT MED, E LANSING, MI 48824 USA. INGHAM CTY HLTH DEPT, LANSING, MI USA. RP LEMON, SJ (reprint author), NCI, DIV CANC PREVENT & CONTROL, CANC PREVENT FELLOWSHIP PROGRAM, BETHESDA, MD 20892 USA. NR 19 TC 6 Z9 6 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV PY 1992 VL 152 IS 11 BP 2238 EP 2242 DI 10.1001/archinte.152.11.2238 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JX151 UT WOS:A1992JX15100009 PM 1444683 ER PT J AU KOCH, MA VOLBERDING, PA LAGAKOS, SW BOOTH, DK PETTINELLI, C MYERS, MW AF KOCH, MA VOLBERDING, PA LAGAKOS, SW BOOTH, DK PETTINELLI, C MYERS, MW TI TOXIC EFFECTS OF ZIDOVUDINE IN ASYMPTOMATIC HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALS WITH CD4+ CELL COUNTS OF 0.50X109/L OR LESS - DETAILED AND UPDATED RESULTS FROM PROTOCOL-019 OF THE AIDS CLINICAL-TRIALS GROUP SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; SYNDROME-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; EXPERIENCE AB Background.-Protocol 019 of the AIDS Clinical Trials Group is a multicenter, double-blind, placebo-controlled trial of zidovudine (3'-azido-3'-deoxythymidine; formerly AZT) in human immunodeficiency virus-infected asymptomatic individuals. The initial results in the stratum of subjects entering with CD4+ cell counts of 0.50 x 10(9)/L or less have been reported, but without a detailed analysis of toxic effects. Methods.-This detailed and updated report analyzes the toxic effects that occurred in 1567 subjects (91% men; 89% white) in this stratum of protocol 019 who received placebo (494 subjects), a 500-mg daily dose of zidovudine (544 subjects), or a 1500-mg daily dose of zidovudine (529 subjects). Hematologic, hepatic, and renal effects and patient-reported symptoms and clinical signs were monitored. Results.-Severe anemia (hemoglobin level, <80 g/L) was associated with both the 500-mg zidovudine group and the 1500-mg group compared with placebo. The estimated 18-month risks of severe anemia were 0.4%, 2.0%, and 9.7% for the placebo, 500-mg zidovudine, and 1500-mg zidovudine groups, respectively. Predictive baseline measures were lower hemoglobin level in the 1500-mg group and the two zidovudine groups combined and lower platelet count in the 500-mg zidovudine group. The risk of a first severe anemia developing was greatest in months 3 through 8 of treatment. Of the 44 subjects with severe anemia in the zidovudine groups, 18 (41%) progressed from mild anemia (hemoglobin level, 95 to 10(9)g/L) to severe anemia on consecutive visits (usually 2 to 4 weeks apart). Severe neutropenia (absolute neutrophil count, <750 X 10(6)/L) did not occur significantly more often in the 500-mg zidovudine group but did in the 1500-mg zidovudine group. Moderate neutropenia (absolute neutrophil count, <1300 X 10(6)/L) did develop significantly more often in the 500-mg zidovudine group (165 subjects) than in the placebo group (71 subjects). Mild (or worse) elevations of bilirubin levels were uncommon but occurred more often with zidovudine. Severe nausea (and/or vomiting) was rare (2.8% of subjects) but was associated with zidovudine. Milder patient-reported events were common, and a number were associated with zidovudine. Conclusion.-Zidovudine at the 500-mg/d dosage appears to be tolerable in many patients with asymptpmatic human immunodeficiency virus infection and CD4+ cell counts of 0.50 X 10(9)/L or less. Increased clinical surveillance for anemia may be warranted in certain patients. C1 RES TRIANGLE INST, CTR EPIDEMIOL & MED STUDIES, RES TRIANGLE PK, NC 27709 USA. UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT BIOSTAT, BOSTON, MA 02115 USA. NIAID, DIV AIDS, BETHESDA, MD 20892 USA. RP KOCH, MA (reprint author), RES TRIANGLE INST, CTR MED ENVIRONM & ENERGY STAT, POB 12194, RES TRIANGLE PK, NC 27709 USA. NR 18 TC 27 Z9 27 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV PY 1992 VL 152 IS 11 BP 2286 EP 2292 DI 10.1001/archinte.152.11.2286 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA JX151 UT WOS:A1992JX15100016 PM 1359846 ER PT J AU SHERMAN, ME SCHIFFMAN, MH EROZAN, YS WACHOLDER, S KURMAN, RJ AF SHERMAN, ME SCHIFFMAN, MH EROZAN, YS WACHOLDER, S KURMAN, RJ TI THE BETHESDA SYSTEM - A PROPOSAL FOR REPORTING ABNORMAL CERVICAL SMEARS BASED ON THE REPRODUCIBILITY OF CYTOPATHOLOGIC DIAGNOSES SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ATYPICAL PAPANICOLAOU SMEARS; INTRAEPITHELIAL NEOPLASIA; GYNECOLOGIC CYTODIAGNOSIS; RETROSPECTIVE EVALUATION; SQUAMOUS ATYPIA; MILD ATYPIA; FOLLOW-UP; CYTOLOGY; COLPOSCOPY; CARCINOMA AB In the Bethesda System, noninvasive squamous abnormalities are classified as atypical squamous cells of undetermined significance (ASQUS), low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions. The Bethesda System eliminates two diagnostic distinctions that are made in the dysplasia/carcinoma in situ and cervical intraepithelial neoplasia (CIN) classifications, CIN1 vs koilocytotic atypia and CIN2 vs CIN3, and maintains three others, negative vs ASQUS, ASQUS vs koilocytotic atypia, and CIN1 vs CIN2. To determine whether the diagnostic distinctions preserved in the Bethesda System are made more consistently than those eliminated, we analyzed the interobserver reproducibility of two cytopathologists in classifying 257 smears. The findings indicate that the distinctions retained in the Bethesda System are more reproducible than those eliminated. Specifically, cases classified as koilocytotic atypia were distinguished from CIN1 no more reproducibly than predicted by chance, whereas CIN2 and CIN3 were distinguished as consistently as any other pair of diagnoses examined. In 13 cases in which there was interobserver discordance, one reviewer classified the smear as ASQUS and the other reviewer diagnosed CIN2 or CIN3. The findings in this study suggest that smears showing koilocytotic atypia and/or CIN1 may be reported as low-grade squamous intraepithelial lesions without further specification. In contrast, smears showing high-grade squamous intraepithelial lesions may be further classified as CIN2 or CIN3 in accordance with the Bethesda guidelines. Since the diagnosis of ASQUS is applied to smears showing a wide spectrum of changes, management of patients with the diagnosis of ASQUS will be facilitated by providing an explanatory note and/or recommendations when appropriate. C1 NEI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP SHERMAN, ME (reprint author), JOHNS HOPKINS UNIV HOSP,SCH MED,DEPT PATHOL,ROOM 406,600 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 33 TC 44 Z9 44 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 1992 VL 116 IS 11 BP 1155 EP 1158 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA JW636 UT WOS:A1992JW63600020 PM 1444745 ER PT J AU BLOCK, MI ALEXANDER, HR NORTON, JA AF BLOCK, MI ALEXANDER, HR NORTON, JA TI CHOLERA-TOXIN PRETREATMENT PROTECTS AGAINST TUMOR-NECROSIS-FACTOR LETHALITY WITHOUT COMPROMISING TUMOR RESPONSE TO THERAPY SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 45TH ANNUAL CANCER SYMP OF THE SOC OF SURGICAL ONCOLOGY CY MAR 16, 1992 CL NEW YORK, NY SP SOC SURG ONCOL ID INTRACELLULAR CAMP; ADENYLATE-CYCLASE; GENE-EXPRESSION; RESISTANT CELLS; FACTOR RECEPTOR; G-PROTEINS; LIPOPOLYSACCHARIDE; IDENTIFICATION; EFFICACY; TOXICITY AB Antitumor therapy with tumor necrosis factor is limited by systemic toxic effects. We studied whether cholera toxin, a bacterial exotoxin that adenosine diphosphate-ribosylates the alpha-subunit of G(s) proteins, could separate the lethal from the antitumor effects of tumor necrosis factor. A single dose of intravenous cholera toxin protected non-tumor-bearing mice from a lethal dose of Escherichia coli endotoxin administered 6 or 24 hours later. On the basis of these results, tumor-bearing mice were randomized to receive either cholera toxin or saline, followed 6 hours later by either human tumor necrosis factor (400 mug/kg) or saline. Tumor-bearing mice pretreated with cholera toxin had (1) reduced treatment-related mortality (0/11 vs 5/11 for saline controls) and (2) tumor regression similar to that of controls. In a separate experiment in tumor-bearing mice, intravenous human tumor necrosis factor treatment induced an increase in serum levels of murine tumor necrosis factor to a peak of 500 pg/mL at 1 hour in saline-pretreated controls, while a similar increase could not be detected in those mice pretreated with cholera toxin. These results suggest that pretreatment with cholera toxin can reduce the endogenous tumor necrosis factor response to administered tumor necrosis factor and separate the lethal from the antitumor effects. Cholera toxin may prove to be a useful tool for investigating the mechanisms underlying the varied effects of tumor necrosis factor. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NR 22 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD NOV PY 1992 VL 127 IS 11 BP 1330 EP 1334 PG 5 WC Surgery SC Surgery GA JW884 UT WOS:A1992JW88400015 PM 1444796 ER PT J AU MCNAMARA, JR JENNER, JL LI, ZL WILSON, PWF SCHAEFER, EJ AF MCNAMARA, JR JENNER, JL LI, ZL WILSON, PWF SCHAEFER, EJ TI CHANGE IN LDL PARTICLE-SIZE IS ASSOCIATED WITH CHANGE IN PLASMA TRIGLYCERIDE CONCENTRATION SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE LOW DENSITY LIPOPROTEINS; LOW DENSITY LIPOPROTEIN SUBSPECIES; TRIGLYCERIDES; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; GRADIENT GEL ELECTROPHORESIS ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; POSTMENOPAUSAL WOMEN; SUBCLASS PATTERNS; RISK-FACTORS; SUBFRACTIONS; APOLIPOPROTEINS; CHOLESTEROL; FRACTIONS; AGE AB Low density lipoprotein (LDL) particle size is inversely associated with plasma triglyceride concentration in cross-sectional analyses. In the present study, changes in the LDL particle size of 227 participants of the Framingham Offspring Study were analyzed longitudinally by nondenaturing gradient gel electrophoresis at two examinations that were separated by 3-4 years. All subjects had triglyceride concentration <400 mg/dl at both exams. Using laser scanning densitometry to assess mean LDL particle size, 56% of samples displayed a change in size: 41% had a one-band size change, 13% had a two-band change, an 2% had a three-band change. These changes in size corresponded to a 15% change in pattern type, based on pattern A and B terminology. There was a significant inverse association between change in LDL size and change in triglyceride (p<0.0001) and glucose (p<0.004) concentrations, body weight (p<0.02), and age (p<0.03). There was also a significant positive association with change in high density lipoprotein (HDL) cholesterol concentration (p<0.0001). Change in LDL cholesterol concentration, as calculated by use of the Friedewald formula, however, showed no significant association with change in LDL size (p<0.9). There was also no significant association with change in smoking or blood pressure, but there was a nonsignificant inverse trend associated with alcohol intake (p<0.08). Women had more significant changes than men, but the relation between change in LDL size and change in lipids was the same for women and men. In stepwise regression analyses of biochemical indices, change in triglyceride concentration produced the best single-variable model (r=0.460). When change in HDL cholesterol concentration was added to the model, the r value increased slightly to 0.481 for the two-variable model. No other variables entered the model. We conclude that the amount of circulating triglyceride appears to be the single most important factor affecting LDL particle size and that LDL size can be modulated by changes in plasma triglyceride concentration. C1 NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA. RP MCNAMARA, JR (reprint author), TUFTS UNIV,USDA,HUMAN NUTR RES CTR,LIPID METAB LAB,711 WASHINGTON ST,BOSTON,MA 02111, USA. FU NHLBI NIH HHS [HL-35243, HV 83-03] NR 34 TC 225 Z9 233 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD NOV PY 1992 VL 12 IS 11 BP 1284 EP 1290 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JX302 UT WOS:A1992JX30200007 PM 1420088 ER PT J AU KANG, AH KRANE, SM LEROY, EC RIGGS, BL GOLDBERG, VM AF KANG, AH KRANE, SM LEROY, EC RIGGS, BL GOLDBERG, VM TI SCIENTIFIC WORKSHOP ON THE BIOLOGY AND PATHOLOGY OF ACQUIRED CONNECTIVE-TISSUE DISEASES SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material RP KANG, AH (reprint author), NIAMS,INFORMAT CLEARINGHOUSE,BOX AMS,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1992 VL 35 IS 11 BP 1289 EP 1295 PG 7 WC Rheumatology SC Rheumatology GA JW730 UT WOS:A1992JW73000006 PM 1445444 ER PT J AU HOFFMAN, GS LEAVITT, RY KERR, GS FAUCI, AS AF HOFFMAN, GS LEAVITT, RY KERR, GS FAUCI, AS TI THE TREATMENT OF WEGENERS GRANULOMATOSIS WITH GLUCOCORTICOIDS AND METHOTREXATE SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LOW-DOSE METHOTREXATE; RHEUMATOID-ARTHRITIS; PULSE METHOTREXATE; THERAPY; AUTOANTIBODIES; EFFICACY; NEUTROPHILS; PNEUMONIA; DISEASES; SAFETY AB Objective. To identify alternatives to daily low-dose cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG). Methods. An open-label pilot study of weekly low-dose methotrexate (MTX) plus glucocorticoids (GC) for treatment of patients with WG was performed. Twenty-nine patients who did not have immediately life-threatening disease were included. Outcome was determined by clinical characteristics, pathologic findings, course of illness, laboratory and radiographic findings, and successful withdrawal of GC therapy. Results. Weekly administration of MTX (at a mean stable dosage of 20 mg) and GC resulted in marked improvement in 76% of the 29 patients. Remission was achieved in 69% of the patients, 7% improved but had intermittent smoldering disease that precluded total withdrawal of GC, and 17% had progressive disease within 2-6 months of starting the study treatment. Two patients who initially achieved remission later had relapses after GC was discontinued. Of those who remain in remission (mean followup time 14.5 months), 72% have not required GC for a mean period of 10 months. Conclusion. Although standard therapy for WG (daily CYC and GC) has dramatically improved outcome in this often-fatal disease, treatment morbidity has led to attempts to identify effective interventions that have less toxicity. Weekly low-dose MTX was shown in this study to be a feasible alternative to CYC in patients whose illness was not immediately life-threatening or in whom prior CYC treatment was ineffective or produced serious toxicity. Although these results are preliminary, they are encouraging and justify further studies in which MTX, CYC, and other alternative therapeutic approaches are compared concurrently. RP HOFFMAN, GS (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 170 Z9 175 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1992 VL 35 IS 11 BP 1322 EP 1329 PG 8 WC Rheumatology SC Rheumatology GA JW730 UT WOS:A1992JW73000011 PM 1445449 ER PT J AU ATKINSON, JC TRAVIS, WD SLOCUM, L EBBS, WL FOX, PC AF ATKINSON, JC TRAVIS, WD SLOCUM, L EBBS, WL FOX, PC TI SERUM ANTI-SS-B/LA AND IGA RHEUMATOID-FACTOR ARE MARKERS OF SALIVARY-GLAND DISEASE-ACTIVITY IN PRIMARY SJOGRENS-SYNDROME SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC SICCA SYNDROME AB Objective. To identify serologic markers of salivary gland disease activity in 43 patients with primary Sjogren's syndrome. Methods. Comparison of salivary gland biopsies (focus scores) and flow rates with serum concentrations of IgA and IgM rheumatoid factor (RF), total serum IgG, serum anti-SS-B/La antibodies, and the erythrocyte sedimentation rate. Results. Serum anti-SS-B/La antibody levels correlated with focus scores (r(s) = 0.477, P < 0.0025). Serum IgA-RF concentrations correlated inversely with stimulated parotid gland salivary flow rates (r(s) = -0.394, P < 0.01). Conclusion. Measuring serum levels of anti-SS-B/La and IgA-RF would be useful when monitoring salivary responses in therapeutic trials, especially in patients with minimal salivary function. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP ATKINSON, JC (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. NR 15 TC 42 Z9 43 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1992 VL 35 IS 11 BP 1368 EP 1372 PG 5 WC Rheumatology SC Rheumatology GA JW730 UT WOS:A1992JW73000017 PM 1445455 ER PT J AU EVANS, GA FARRAR, WL AF EVANS, GA FARRAR, WL TI RETINOBLASTOMA PROTEIN-PHOSPHORYLATION DOES NOT REQUIRE ACTIVATION OF P34CDC2 PROTEIN-KINASE SO BIOCHEMICAL JOURNAL LA English DT Article ID CONTROL GENE CDC2+; CELL-CYCLE; SUSCEPTIBILITY GENE; HISTONE-H1 KINASE; E1A PROTEINS; M-PHASE; PRODUCT; MITOSIS; HOMOLOG; EXPRESSION AB Of the many intracellular events that occur after mitogenic stimulation of cells, the phosphorylation of the retinoblastoma protein (RB) in early G1-phase appears to play a pivotal role in controlling cell-cycle progression. RB phosphorylation results in release from a proliferative block imposed by hypophosphorylated RB. Several investigators have presented evidence, using models produced in vitro, that the serine kinase p34CDC2 phosphorylates RB and is responsible for regulating RB phosphorylation. Using human T-cells as a model, we show that lectin treatment of resting T-cells results in detectable RB phosphorylation by 24 h after treatment. Further, using immunoprecipitation and immunoblotting, no detectable p34CDC2 could be seen until 48 h after lectin stimulation. Analysis of the relative histone H1 activity of p34CDC2, purified by immunoprecipitation, revealed that RB phosphorylation does not parallel increases in p34CDC2 activity as T-cells progress into S-phase, supporting the contention that p34CDC2 activation as a histone H1 kinase is not a critical regulator of RB phosphorylation. Further treatment of activated T-cells, arrested in G1-phase, with interleukin 2 results in a 95% increase in RB phosphorylation within 4 h with no detectable increase in the histone H1 kinase activity of p34CDC2. Together, these data suggest that p34CDC2 activation is not required for early cell-cycle phosphorylation of RB. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. RP EVANS, GA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 32 TC 2 Z9 2 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 NOV 1 PY 1992 VL 287 BP 965 EP 969 PN 3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW485 UT WOS:A1992JW48500042 PM 1332690 ER PT J AU FITZGERALD, DJ PASTAN, I AF FITZGERALD, DJ PASTAN, I TI PSEUDOMONAS EXOTOXIN - RECOMBINANT CONJUGATES AS THERAPEUTIC AGENTS SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article ID GROWTH-FACTOR; FUSION PROTEIN; ANTITUMOR-ACTIVITY; TUMOR-CELLS; RECEPTOR; MICE; IMMUNOTOXIN; TOXIN; IL-2-PE40; ALPHA RP FITZGERALD, DJ (reprint author), NCI,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 31 TC 5 Z9 5 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 1992 VL 20 IS 4 BP 731 EP 734 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA088 UT WOS:A1992KA08800005 PM 1487051 ER PT J AU DETERDING, LJ CURTIS, JF TOMER, KB AF DETERDING, LJ CURTIS, JF TOMER, KB TI TANDEM MASS-SPECTROMETRIC IDENTIFICATION OF EICOSANOIDS - LEUKOTRIENES AND HYDROXYEICOSATETRAENOIC ACIDS SO BIOLOGICAL MASS SPECTROMETRY LA English DT Article ID FAST ATOM BOMBARDMENT; CHARGE-REMOTE FRAGMENTATIONS; PROSTAGLANDIN-H SYNTHASE; IONS; DECOMPOSITION; DISSOCIATION; METABOLITES; CYSTEINE; FAB AB The product ion spectra of the fast atom bombardment (FAB) desorbed [M - H]- ions of leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) have been obtained on a tandem magnetic sector mass spectrometer with introduction by coaxial continuous flow FAB. Upon collisional activation, the product ion spectra of the [M - H]- ions of these derivatives of arachidonic acid reveal structurally informative product ions. The location of the hydroxy groups on the fatty acid chain, and the position and type of the cysteine-containing moiety of the LTs, can be readily determined from the product ion spectra. Tandem mass spectrometry was used to identify 11- and 15-HETE produced in a low-temperature microsomal enzymatic oxidation of arachidonic acid. RP DETERDING, LJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Tomer, Kenneth/E-8018-2013 NR 32 TC 19 Z9 19 U1 0 U2 0 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 NOV PY 1992 VL 21 IS 11 BP 597 EP 609 DI 10.1002/bms.1200211112 PG 13 WC Biophysics; Spectroscopy SC Biophysics; Spectroscopy GA JU830 UT WOS:A1992JU83000011 ER PT J AU ALEXANDER, RC BRESLIN, N MOLNAR, C RICHTER, J MUKHERJEE, S AF ALEXANDER, RC BRESLIN, N MOLNAR, C RICHTER, J MUKHERJEE, S TI COUNTER CLOCKWISE SCALP HAIR WHORL IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Note ID MINOR PHYSICAL ANOMALIES; BRAIN-DEVELOPMENT C1 ST ELIZABETH HOSP,NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. GEORGE WASHINGTON UNIV,DEPT PSYCHIAT & BEHAV SCI,WASHINGTON,DC 20052. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY 10027. CREEDMOOR PSYCHIAT CTR,QUEENS VILLAGE,NY. RP ALEXANDER, RC (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT & HUMAN BEHAV,1020 SANSOM ST,ROOM 1651,PHILADELPHIA,PA 19107, USA. NR 21 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 1992 VL 32 IS 9 BP 842 EP 845 DI 10.1016/0006-3223(92)90089-I PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KA515 UT WOS:A1992KA51500012 PM 1450299 ER PT J AU HEINDEL, JJ POWELL, CJ PASCHALL, CS ARIMURA, A CULLER, MD AF HEINDEL, JJ POWELL, CJ PASCHALL, CS ARIMURA, A CULLER, MD TI A NOVEL HYPOTHALAMIC PEPTIDE, PITUITARY ADENYLATE-CYCLASE ACTIVATING PEPTIDE, MODULATES SERTOLI-CELL FUNCTION-INVITRO SO BIOLOGY OF REPRODUCTION LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; BINDING-SITES; MOLECULAR-IDENTIFICATION; POLYPEPTIDE PACAP; RECEPTORS; MEMBRANES; CULTURE; PROTEIN; VIP AB Pituitary adenylate cyclase-activating peptide (PACAP), a novel hypothalamic peptide that has been shown to exist in several tissues including the testis, was examined for its effects on cultured rat Sertoli cells. PACAP stimulates cAMP accumulation in Sertoli cells cultured from 15-day-old rats in the presence or absence of methylisobutylxanthine, a phosphodiesterase inhibitor, and in the presence of pertussis toxin, a blocker of the adenylate cyclase inhibitory pathway. Maximal stimulation, which is 20-40% of that attainable with FSH, occurs at PACAP concentrations of 10 nM: the ED50 is approximately 100 pM. The ability of PACAP to stimulate Sertoli cell cAMP declines with increasing age of donor animals (15-60 days of age) in a fashion similar to the FSH effect. PACAP stimulation of Sertoli cell cAMP accumulation is additive with submaximal, but not maximal, concentrations of FSH or forskolin. PACAP also stimulates the secretion of lactate, estradiol, and inhibin in a concentration-dependent manner. The stimulation of Sertoli cell cAMP accumulation by PACAP is not altered by a vasoactive intestinal peptide antagonist, and vasoactive intestinal peptide alone does not stimulate cAMP accumulation, indicating that PACAP is not acting via vasoactive intestinal peptide receptors. Further experiments are needed to determine whether PACAP is synthesized within the testis and if so, in which cell types; however, the present data clearly demonstrate that PACAP can modulate Sertoli cell function in vitro. C1 NIEHS,DEV & REPROD TOXICOL GRP,POB 12233,RES TRIANGLE PK,NC 27709. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. TULANE UNIV,US JAPAN BIOMED RES LAB,HEBERT CTR,BELLE CHASSE,LA 70037. NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. NR 25 TC 53 Z9 53 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 1992 VL 47 IS 5 BP 800 EP 806 DI 10.1095/biolreprod47.5.800 PG 7 WC Reproductive Biology SC Reproductive Biology GA JU827 UT WOS:A1992JU82700016 PM 1335766 ER PT J AU NEWBOLD, RR TENG, CT BECKMAN, WC JEFFERSON, WN HANSON, RB MILLER, JV MCLACHLAN, JA AF NEWBOLD, RR TENG, CT BECKMAN, WC JEFFERSON, WN HANSON, RB MILLER, JV MCLACHLAN, JA TI FLUCTUATIONS OF LACTOFERRIN PROTEIN AND MESSENGER-RIBONUCLEIC-ACID IN THE REPRODUCTIVE-TRACT OF THE MOUSE DURING THE ESTROUS-CYCLE SO BIOLOGY OF REPRODUCTION LA English DT Article ID UTERINE SECRETIONS; GENE-EXPRESSION; SEMINAL-VESICLE; UTERUS; LACTOTRANSFERRIN; ESTRADIOL; DIETHYLSTILBESTROL; IMPLANTATION; PURIFICATION; LOCALIZATION AB The physiological role of lactoferrin (LF), the major estrogen-inducible protein in the murine uterus, is unclear; however, LF may be a useful marker for the study of estrogen action in the uterus. Thus, the expression of LF mRNA and the localization of the protein in genital tract tissues and secretions of female mice (6-8 wk old) at different stages of the estrous cycle were investigated. Uterine luminal fluid (ULF) was analyzed for LF by means of gel electrophoresis and Western blot techniques; LF mRNA and protein were identified in reproductive tract tissues through in situ hybridization and immunocytochemistry. At diestrus, the level of LF mRNA was low, and staining for the protein was very light in uterine epithelial cells; LF was undetectable in ULF. At proestrus, LF mRNA and protein increased in the uterine epithelium and LF was readily detectable in ULF. LF mRNA and protein reached the highest levels at estrus. At early metestrus as compared to estrus, LF mRNA and protein were detected in decreasing amounts in uterine epithelial cells; the protein was undetected in ULF. By late metestrus and diestrus, LF mRNA and protein returned to a low level, and the protein was undetectable in ULF. LF protein was also demonstrated by immunocytochemistry in the epithelium of the oviduct, cervix, and vagina. LF protein fluctuation similar to that observed in the uterus was seen in these tissues; however, the uterus demonstrated the most dramatic changes in the number of epithelial cells involved in LF production during the estrous cycle. In summary, LF mRNA and its expression in uterine epithelial cells of the mouse varied with the stage of the estrous cycle. These results, combined with previously reported findings that LF is a major constituent of mouse ULF under the influence of estrogen, suggest that LF may play an important role in normal reproductive processes. RP NEWBOLD, RR (reprint author), NIEHS,DIV INTRAMURAL RES,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 42 TC 54 Z9 55 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 1992 VL 47 IS 5 BP 903 EP 915 DI 10.1095/biolreprod47.5.903 PG 13 WC Reproductive Biology SC Reproductive Biology GA JU827 UT WOS:A1992JU82700027 PM 1477216 ER PT J AU CLERICI, M ROILIDES, E BUTLER, KM DEPALMA, L VENZON, D SHEARER, GM PIZZO, PA AF CLERICI, M ROILIDES, E BUTLER, KM DEPALMA, L VENZON, D SHEARER, GM PIZZO, PA TI CHANGES IN T-HELPER CELL-FUNCTION IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN DURING DIDANOSINE THERAPY AS A MEASURE OF ANTIRETROVIRAL ACTIVITY SO BLOOD LA English DT Article ID AIDS-RELATED COMPLEX; MIXED LYMPHOCYTE-REACTION; PLACEBO-CONTROLLED TRIAL; HIV INFECTION; IMMUNE FUNCTION; CLINICAL COURSE; HOMOSEXUAL MEN; ZIDOVUDINE AZT; DOUBLE-BLIND; TYPE-1 C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NCI,CTR BIOL,DIV CANC,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,CTR DIAG,DIV CANC,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. CHILDRENS HOSP,NATL MED CTR,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. RI Venzon, David/B-3078-2008 NR 29 TC 45 Z9 45 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1992 VL 80 IS 9 BP 2196 EP 2202 PG 7 WC Hematology SC Hematology GA JW436 UT WOS:A1992JW43600006 PM 1421391 ER PT J AU KREITMAN, RJ CHAUDHARY, VK KOZAK, RW FITZGERALD, DJP WALDMANN, TA PASTAN, I AF KREITMAN, RJ CHAUDHARY, VK KOZAK, RW FITZGERALD, DJP WALDMANN, TA PASTAN, I TI RECOMBINANT TOXINS CONTAINING THE VARIABLE DOMAINS OF THE ANTI-TAC MONOCLONAL-ANTIBODY TO THE INTERLEUKIN-2 RECEPTOR KILL MALIGNANT-CELLS FROM PATIENTS WITH CHRONIC LYMPHOCYTIC-LEUKEMIA SO BLOOD LA English DT Article ID MULTIVARIATE SURVIVAL ANALYSIS; PSEUDOMONAS EXOTOXIN; DIPHTHERIA-TOXIN; FUSION PROTEIN; CYTO-TOXICITY; TARGET-CELLS; FRAGMENT-A; IMMUNOTOXIN; CYTOTOXICITY; EXPRESSION C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,METAB BRANCH,BETHESDA,MD 20892. US FDA,CBER,DIV CYTOKINE BIOL,BETHESDA,MD 20014. NR 32 TC 44 Z9 46 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1992 VL 80 IS 9 BP 2344 EP 2352 PG 9 WC Hematology SC Hematology GA JW436 UT WOS:A1992JW43600026 PM 1421405 ER PT J AU LIANG, CT BARNES, J SEEDOR, JG QUARTUCCIO, HA BOLANDER, M JEFFREY, JJ RODAN, GA AF LIANG, CT BARNES, J SEEDOR, JG QUARTUCCIO, HA BOLANDER, M JEFFREY, JJ RODAN, GA TI IMPAIRED BONE ACTIVITY IN AGED RATS - ALTERATIONS AT THE CELLULAR AND MOLECULAR-LEVELS SO BONE LA English DT Article DE BONE INDUCTION; MARROW ABLATION; OSTEOCALCIN; OSTEOPONTIN; COLLAGEN; ALKALINE PHOSPHATASE; AGING ID GROWTH-HORMONE; POSTMENOPAUSAL OSTEOPOROSIS; MESSENGER-RNA; CARTILAGE; CELLS; DEXAMETHASONE; COLLAGENASE; EXPRESSION; ESTROGEN; CLONING AB We have used a model of rapid bone induction and resorption in rats initiated by the removal of bone marrow to define age-associated deficits. Here we report the sequential expression of various genes implicated in the formation and removal of bone following marrow ablation. Significant increases in alkaline phosphatase and procollagen alpha1(I) mRNA were observed by day 5, and of osteocalcin and osteopontin by day 6. At their peak, these mRNA levels were elevated three- to eight-fold and correlated with histological evidence of bone formation. No change in collagen II mRNA was observed, indicating that there was no cartilage phase. Collagenase activity increased 10-fold at day 9 and coincided with the beginning of bone resorption. Actin mRNA, a reference gene marker, remained at constant levels. Comparison of the response between adult (6 mo.) and old (24 mo.) rats showed the same temporal pattern, but a lower expression of bone-related genes in older rats. Histological examination also showed that the bone volume and osteoblast number at day 6 were significantly lower in old rats. Furthermore, the percentage of mineralized bone was greatly reduced in the aged rat. This model system is currently being used to evaluate the effectiveness of interventions to up-regulate the bone activity in senescent rats. C1 MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. ALBANY MED CTR,ALBANY,NY 12208. MERCK SHARP & DOHME LTD,W POINT,PA 19486. RP LIANG, CT (reprint author), NIA,GERONTOL RES CTR,BALTIMORE,MD 21224, USA. NR 29 TC 91 Z9 95 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD NOV-DEC PY 1992 VL 13 IS 6 BP 435 EP 441 DI 10.1016/8756-3282(92)90087-D PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KA287 UT WOS:A1992KA28700006 PM 1476822 ER PT J AU HANNA, E DUFOUR, MC ELLIOTT, S STINSON, F HARFORD, TC AF HANNA, E DUFOUR, MC ELLIOTT, S STINSON, F HARFORD, TC TI DYING TO BE EQUAL - WOMEN, ALCOHOL, AND CARDIOVASCULAR-DISEASE SO BRITISH JOURNAL OF ADDICTION LA English DT Note ID CONSUMPTION; MORTALITY; HEART; STROKE; RISK; MEN AB This data note explores the relationship of gender, alcohol consumption and premature cardiovascular disease (MCVD). Data on the 8164 deaths attributed to MCVD from the National Mortality Followback Study (NMFS) were analyzed controlling for gender and consumption. Women who are heavy drinkers die young at a rate equal to that of men who drink heavily. In light of this, we recommend that future research and preventive efforts in this area include females as subjects and alcohol as a major risk factor. C1 CSR INC,WASHINGTON,DC 20005. NIAAA,WASHINGTON,DC 20005. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP HANNA, E (reprint author), NIAAA,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20857, USA. NR 18 TC 16 Z9 16 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD NOV PY 1992 VL 87 IS 11 BP 1593 EP 1597 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA JX830 UT WOS:A1992JX83000010 PM 1458038 ER PT J AU HAKKOLA, J MAENPAA, J MAYER, RT PARK, SS GELBOIN, HV PELKONEN, O AF HAKKOLA, J MAENPAA, J MAYER, RT PARK, SS GELBOIN, HV PELKONEN, O TI 7-ALKOXYQUINOLINE O-DEALKYLATION BY MICROSOMES FROM HUMAN LIVER AND PLACENTA SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE 7-ALKOXYQUINOLINE; CYTOCHROME P450; HUMAN LIVER; HUMAN PLACENTA; CIGARETTE SMOKING ID MONOCLONAL-ANTIBODIES; RECOMMENDED NOMENCLATURE; MONOOXYGENASE ACTIVITIES; P450 SUPERFAMILY; HUMAN-TISSUES; CYTOCHROME-P-450; RAT; METABOLISM; ASSAY; MOUSE AB 1 The O-dealkylation of seven 7-alkoxyquinoline derivatives by human hepatic and placental microsomes and the effect of maternal cigarette smoking on placental 7-alkoxyquinoline metabolism was studied. 2 None of several monoclonal antibodies to isoenzymes of cytochrome P450 had a clear effect on metabolism of the compounds by liver microsomes. 3 Maternal cigarette smoking induced the O-dealkylation of all of the 7-alkoxyquinoline derivatives, being greatest for 7-butoxy- and 7-benzyloxyquinoline. 4 Placental 7-alkoxyquinoline metabolism induced by smoking was partially inhibited by the monoclonal antibody 1-7-1 raised against 3-methylcholanthrene-induced rat liver P450. 5 None of the 7-alkoxyquinoline O-dealkylations could be assigned specifically to any known P450 isoenzyme in human liver or placenta. C1 UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. USDA ARS,US HORT RES LAB,ORLANDO,FL 32803. NR 22 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD NOV PY 1992 VL 34 IS 5 BP 415 EP 420 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JX835 UT WOS:A1992JX83500006 PM 1467136 ER PT J AU BERNSTEIN, EF SPIELVOGEL, RL TOPOLSKY, DL AF BERNSTEIN, EF SPIELVOGEL, RL TOPOLSKY, DL TI RECURRENT NEUTROPHILIC ECCRINE HIDRADENITIS SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID MYELOGENOUS LEUKEMIA; PYODERMA GANGRENOSUM; CHEMOTHERAPY; DERMATOSIS AB Neutrophilic eccrine hidradenitis (NEH) is a neutrophilic dermatosis primarily affecting the eccrine glands, and most commonly seen in patients undergoing chemotherapy for treatment of a malignancy. Rapid diagnosis may avert unnecessary changes in therapy to treat conditions which clinically mimic NEH. We describe a patient who developed NEH on three separate occasions provoked by two different chemotherapeutic agents-cytarabine and mitoxantrone. The lesions were morphologically distinct and differed in their anatomical distribution during each episode. The response to intravenous corticosteroids was dramatic, but lesions recurred after their withdrawal. This case illustrates the potential diversity of clinical lesions in a single patient with NEH, and its response to systemically administered corticosteroids. C1 HAHNEMANN UNIV,SCH MED,DIV DERMATOL,PHILADELPHIA,PA 19102. HAHNEMANN UNIV,SCH MED,DEPT NEOPLAST DIS,PHILADELPHIA,PA 19102. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. RP BERNSTEIN, EF (reprint author), THOMAS JEFFERSON UNIV,DEPT DERMATOL,233 S 10TH ST,SUITE 450,PHILADELPHIA,PA 19107, USA. NR 25 TC 23 Z9 23 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 1992 VL 127 IS 5 BP 529 EP 533 DI 10.1111/j.1365-2133.1992.tb14854.x PG 5 WC Dermatology SC Dermatology GA JX318 UT WOS:A1992JX31800016 PM 1467295 ER PT J AU ZAHM, SH BLAIR, A WEISENBURGER, DD AF ZAHM, SH BLAIR, A WEISENBURGER, DD TI SEX-DIFFERENCES IN THE RISK OF MULTIPLE-MYELOMA ASSOCIATED WITH AGRICULTURE SO BRITISH JOURNAL OF INDUSTRIAL MEDICINE LA English DT Letter C1 UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68105. RP ZAHM, SH (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,ROCKVILLE,MD, USA. NR 7 TC 13 Z9 13 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1072 J9 BRIT J IND MED PD NOV PY 1992 VL 49 IS 11 BP 815 EP 816 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JX072 UT WOS:A1992JX07200014 PM 1463686 ER PT J AU CAPLAN, LJ BARR, RA AF CAPLAN, LJ BARR, RA TI CONTEXT EFFECTS ON CATEGORY MEMBERSHIP AND TYPICALITY JUDGMENTS SO BULLETIN OF THE PSYCHONOMIC SOCIETY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0090-5054 J9 B PSYCHONOMIC SOC PD NOV PY 1992 VL 30 IS 6 BP 467 EP 467 PG 1 WC Psychology, Mathematical SC Psychology GA JV167 UT WOS:A1992JV16700321 ER PT J AU GREENWALD, S GERBER, L AF GREENWALD, S GERBER, L TI THE AMERICANS WITH DISABILITIES ACT SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Article RP GREENWALD, S (reprint author), NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PD NOV PY 1992 VL 41 IS 7 BP 5 EP 7 PG 3 WC Rheumatology SC Rheumatology GA KA095 UT WOS:A1992KA09500003 PM 1472957 ER PT J AU FIELDING, LP FENOGLIOPREISER, CM FREEDMAN, LS AF FIELDING, LP FENOGLIOPREISER, CM FREEDMAN, LS TI THE FUTURE OF PROGNOSTIC FACTORS IN OUTCOME PREDICTION FOR PATIENTS WITH CANCER SO CANCER LA English DT Article DE CANCER; PROGNOSTIC FACTORS; STAGING; OUTCOME; TUMOR IMMUNITY; FLOW CYTOMETRY; MOLECULAR MARKERS; PROGNOSTIC INDEXES ID LARGE BOWEL-CANCER; HUMAN-BREAST CANCER; NUCLEOLAR ORGANIZER REGIONS; MINIMAL RESIDUAL DISEASE; BONE-MARROW; MONOCLONAL-ANTIBODIES; CELL-PROLIFERATION; COLORECTAL-CANCER; INVITRO AMPLIFICATION; C-ERBB-2 ONCOPROTEIN AB The anatomic description of the extent of tumor spread (tumor staging) assists clinical management, facilitates communication among physicians, is an essential part of randomized controlled trials, and may help in the counseling patients and their families. However, in recent years, additional "prognostic factors" have been defined, many of which assess or reflect the biologic behavior of malignant neoplasms. Other measures of tumor biochemistry address the natural history of neoplastic development and often are included in a discussion of new prognostic factors. This review article summarizes current knowledge and thinking related to tumor prognostic factors in four areas by providing: (1) a definition and principles of anatomic spread of tumor (staging) and some suggestions for improvement, (2) a description of some examples of additional factors of prognostic significance, (3) some statistical methods to evaluate prognostic factors, and (4) an examination of the possible future of summary statements of outcome (i.e., prognostic indexes). C1 YALE UNIV,SCH MED,NEW HAVEN,CT 06510. UNIV CINCINNATI,COLL MED,DEPT PATHOL & LAB MED,CINCINNATI,OH 45221. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. RP FIELDING, LP (reprint author), ST MARYS HOSP,DEPT SURG,WATERBURY,CT 06706, USA. NR 98 TC 142 Z9 145 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1992 VL 70 IS 9 BP 2367 EP 2377 DI 10.1002/1097-0142(19921101)70:9<2367::AID-CNCR2820700927>3.0.CO;2-B PG 11 WC Oncology SC Oncology GA JU762 UT WOS:A1992JU76200026 PM 1394064 ER PT J AU HEINEMAN, EF OLSEN, JH POTTERN, LM GOMEZ, M RAFFN, E BLAIR, A AF HEINEMAN, EF OLSEN, JH POTTERN, LM GOMEZ, M RAFFN, E BLAIR, A TI OCCUPATIONAL RISK-FACTORS FOR MULTIPLE-MYELOMA AMONG DANISH MEN SO CANCER CAUSES & CONTROL LA English DT Article DE DENMARK; INDUSTRY; METALWORKING; MULTIPLE MYELOMA; OCCUPATION; PHTHALATES; RISK FACTORS; VINYL CHLORIDE AB A large population-based case-control study evaluated occupational exposures in 1,098 Danish males diagnosed with multiple myeloma from 1970 to 1984 and in 4,169 age- and gender-matched controls alive at the time of case-diagnosis. Industrial histories were obtained from the Supplementary Pension Fund which, since 1964, has recorded employments of adult Danes; occupation came from subjects' most recent tax records. Four industrial hygienists created a job-exposure matrix for 47 substances based on 15,000 unique industry/occupation combinations in subjects' histories. Risk of myeloma was significantly elevated among road and railroad workers, precision metalworkers, and workers in the transportation and communication industries. Risk increased significantly with duration of employment in: production of synthetic yarns, plastic packaging, and miscellaneous chemical compounds; fabricating structural metal and stationary tanks; body factories; electrical plants; and retail sale of paint and wallpaper. Risks of myeloma were elevated, though statistically nonsignificantly, in all categories of exposure to gasoline and engine exhausts. Risks rose with likelihood and duration of exposure to phthalates, and were statistically significant and nearly fivefold with probable exposure to vinyl chloride for five or more years. After adjusting for multiple exposures and disregarding exposures within 10 years of diagnosis (or selection as a control), probable exposure to vinyl chloride was associated with increased risk of myeloma, which rose to fivefold with longer exposure. Associations with gasoline, engine exhausts, and phthalates persisted, but were inconsistent with duration and probability of exposure. Previously reported associations with agriculture were not confirmed by these data. RP HEINEMAN, EF (reprint author), NCI,OCCUPAT STUDIES SECT,6130 EXECUT BLVD,ROOM 418,ROCKVILLE,MD 20852, USA. NR 0 TC 51 Z9 51 U1 0 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 1992 VL 3 IS 6 BP 555 EP 568 DI 10.1007/BF00052753 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JW246 UT WOS:A1992JW24600008 PM 1420859 ER PT J AU MILLER, RW AF MILLER, RW TI CHILDHOOD LEUKEMIA AND NEONATAL EXPOSURE TO LIGHTING IN NURSERIES SO CANCER CAUSES & CONTROL LA English DT Note RP MILLER, RW (reprint author), NCI,CLIN EPIDEMIOL BRANCH,EPN 400,BETHESDA,MD 20892, USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 1992 VL 3 IS 6 BP 581 EP 582 DI 10.1007/BF00052755 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JW246 UT WOS:A1992JW24600010 PM 1420860 ER PT J AU BERG, SL BALIS, FM MCCULLY, CL PARKER, GA MURPHY, RF POPLACK, DG AF BERG, SL BALIS, FM MCCULLY, CL PARKER, GA MURPHY, RF POPLACK, DG TI INTRATHECAL 5-FLUOROURACIL IN THE RHESUS-MONKEY SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article ID NEUROTOXICITY; METHOTREXATE; CHEMOTHERAPY AB Because meningeal spread of both leukemia and solid tumors remains a difficult therapeutic problem, there is a compelling need to develop new agents for intrathecal administration. 5-Fluorouracil (5FU), an active anticancer agent, penetrates into the central nervous system to some degree following intravenous dosing. Significant systemic toxicity, however, is associated with this route of administration. Therefore, the pharmacokinetic behavior of 5FU following its intrathecal administration was studied in a rhesus monkey model. After a 10-mg intraventricular dose, the disappearance of the drug from ventricular cerebrospinal fluid was monoexponential, the half-life being 51 min; the area under the concentration-time curve (AUC) being greater than 18 mM h-1; and the peak ventricular 5FU concentrations ranging between 10 and 15 mM. After a 1-mg intralumbar dose, the AUC was 1235 muM h-1. No toxicity was observed following intraventricular administration of 5FU. After intralumbar administration of either a 10-mg or a 1-mg dose, however, local toxicity was observed in the lumbar spinal cord. These findings suggest that intrathecal administration of 5FU is not presently a feasible means of achieving cytotoxic cerebrospinal fluid concentrations. RP BERG, SL (reprint author), NCI,PEDIAT BRANCH,BLDG 10,RM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 3 Z9 3 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 NOV PY 1992 VL 31 IS 2 BP 127 EP 130 DI 10.1007/BF00685099 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA JX518 UT WOS:A1992JX51800009 PM 1451233 ER PT J AU WINN, DM LI, FP ROBISON, LL MULVIHILL, JJ DAIGLE, AE FRAUMENI, JF AF WINN, DM LI, FP ROBISON, LL MULVIHILL, JJ DAIGLE, AE FRAUMENI, JF TI A CASE-CONTROL STUDY OF THE ETIOLOGY OF EWING SARCOMA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHILDHOOD-CANCER IRESCC; MULTIMODAL THERAPY; CONTROL SELECTION; MATERNAL SMOKING; NEURO-BLASTOMA; BIRTH-DEFECTS; BRAIN-TUMORS; BONE CANCER; CHILDREN; RISK AB An interview case-control study was undertaken to search for risk factors for Ewing's sarcoma. The 208 cases, aged 5 months to 22 years at diagnosis and all white but one, were identified from hospitals participating in the intergroup Ewing's Sarcoma Study therapeutic trials. Two controls were sought for each case: a sibling control and an age-matched regional population control identified through random-digit dialing telephone procedures. A questionnaire was administered to the parents of cases and controls. Parents were more likely to have smoked during the pregnancy with the case than during the pregnancy with the unaffected sibling. Risks rose with the number of cigarettes the mother smoked per day during the pregnancy. Concepti exposed to less than 1 pack/day were at 3.2 times the risk, and those exposed to 1 pack or more were at 6.7 times the risk of the nonexposed. However, risks associated with smoking were lower and not statistically significant in analyses using the region-matched controls. Hernias, mostly umbilical and inguinal, were diagnosed six times more frequently among the cases compared to region-matched controls. However, hernias occurred in just 10% of cases, and the matched siblings had hernias diagnosed with the same frequency as the cases. An apparent excess of heart disorders among cases versus siblings seems likely to be an artifact of increased medical surveillance of cases. Fathers of Ewing's sarcoma cases were 2 times more likely to work as farmers at the time of conception than fathers of region-matched controls and 3 times more likely to have farming as their usual occupation, but the findings did not reach statistical significance. Ewing's sarcoma was not linked to other factors which were examined: antecedent bone trauma-cancer among relatives; demographic characteristics including religion, education, and income; and anthropomorphic measures (child's birth height or weight or parents' height or weight). Although a wide range of demographic, maternal reproductive, child health, occupational, and family history data were obtained, Ewing's sarcoma remains a cancer of unknown cause. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV PITTSBURGH,PITTSBURGH,PA 15260. IMMUNE RESPONSE CORP,CARLSBAD,CA. NCI,BETHESDA,MD 20892. RP WINN, DM (reprint author), CTR DIS CONTROL,NATL CTR HLTH STAT,DIV HLTH INTERVIEW STAT,6525 BELCREST RD,ROOM 850,HYATTSVILLE,MD 20782, USA. NR 55 TC 33 Z9 35 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV-DEC PY 1992 VL 1 IS 7 BP 525 EP 532 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JY264 UT WOS:A1992JY26400001 PM 1302564 ER PT J AU POTISCHMAN, N BYERS, T HOUGHTON, L ROOT, M NEMOTO, T CAMPBELL, TC AF POTISCHMAN, N BYERS, T HOUGHTON, L ROOT, M NEMOTO, T CAMPBELL, TC TI EFFECTS OF BREAST-CANCER TREATMENTS ON PLASMA NUTRIENT LEVELS - IMPLICATIONS FOR EPIDEMIOLOGIC STUDIES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERUM VITAMIN-A; BETA-CAROTENE; ESTROGEN BINDING; ALPHA-TOCOPHEROL; TAMOXIFEN; DIET; LIPIDS; HYPOCHOLESTEROLEMIA; RETINOL; HISTORY AB The interpretation of case-control studies in which blood nutrient levels are examined as etiological factors in cancer is complicated by the possibility that either the disease or its treatment may alter these levels. Circulating levels of selected nutrients were examined prior to diagnostic biopsy and compared with levels 3 to 4 months after diagnosis among 71 women with breast cancer and 95 women with benign breast disease. Among women with benign breast disease or women with breast cancer who were not given postsurgical adjuvant drug therapy, levels of alpha-carotene, lycopene, alpha-tocopherol, cholesterol, and triglycerides did not change over time. In contrast, women who received chemotherapy had increased levels of cholesterol, retinol, and alpha- and gamma-tocopherol, and women on antiestrogen therapy showed increased levels of triglycerides and alpha-tocopherol. Overall, the concentrations of carotenoids (lycopene, alpha-carotene, and beta-carotene) did not change in breast cancer cases, although subgroup analyses showed increased levels of beta-carotene among cases not receiving drug treatment and decreased levels among those receiving antiestrogens. In summary, blood levels of some nutrients did not appear to be affected by breast cancer or its treatments, but changes were noted for levels of plasma lipids, tocopherols, retinol, and beta-carotene. Those investigating the etiological relationship between breast cancer and circulating nutrients need to consider these effects in designing and interpreting epidemiological studies. C1 CTR DIS CONTROL,CTR CHRON DIS PREVENT & HLTH PROMOT,DIV NUTR,EPIDEMIOL BRANCH,ATLANTA,GA 30333. CORNELL UNIV,DIV NUTR,ITHACA,NY 14853. SISTERS HOSP,CTR BREAST CARE,BUFFALO,NY 14214. RP POTISCHMAN, N (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,ENVIRONM STUDIES SECT,BETHESDA,MD 20892, USA. NR 30 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV-DEC PY 1992 VL 1 IS 7 BP 555 EP 559 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JY264 UT WOS:A1992JY26400007 PM 1302568 ER PT J AU ELLWEIN, LB PURTILO, DT AF ELLWEIN, LB PURTILO, DT TI CELLULAR PROLIFERATION AND GENETIC EVENTS INVOLVED IN THE GENESIS OF BURKITT-LYMPHOMA (BL) IN IMMUNE COMPROMISED PATIENTS SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID EPSTEIN-BARR-VIRUS; LYMPHOPROLIFERATIVE DISEASES; BLADDER CARCINOGENESIS; IMMUNODEFICIENCY; CELLS; MODEL; MICE; LEUKEMIA; TRANSFORMATION; LEUKEMOGENESIS AB A mathematical model simulating lymphomagenesis based on the two-hit theory of carcinogenesis is presented by contrasting the biologic variables responsible for a high risk of developing Burkitt lymphoma [BL] in three immunosuppressed groups with that of nonendemic BL. In this model, the pro-B lymphocyte is considered to be the target for BL-specific translocations such as t[8;14]. With repeated mitosis, the target cell pool expands in the high-risk individual, and, thereby, the opportunities for a spontaneous translocation to arise are increased. The chromosomal translocation endows the target cell with survival advantages, and, hence, lymphoma develops. Modeling results demonstrate that this increased cell proliferation is sufficient in accounting entirely for the increase in tumor prevalence. Preventing enhanced cellular proliferation by obviating immune deficiency and treating patients with agents that restore immunity or have antiviral and antiproliferative properties prior to conversion from polyclonal B-cell proliferation to monoclonal malignancy could obviate the development of BL. C1 UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68105. UNIV NEBRASKA,MED CTR,DEPT PEDIAT,OMAHA,NE 68105. UNIV NEBRASKA,MED CTR,EPPLEY INST RES CANC & ALLIED DIS,OMAHA,NE 68105. RP ELLWEIN, LB (reprint author), NIH,BLDG 31,RM 6A08,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA30196] NR 47 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD NOV PY 1992 VL 64 IS 1 BP 42 EP 48 DI 10.1016/0165-4608(92)90321-X PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA KD817 UT WOS:A1992KD81700008 PM 1458449 ER PT J AU BOWDEN, PE WOODWORTH, CD DONIGER, J DIPAOLO, JA AF BOWDEN, PE WOODWORTH, CD DONIGER, J DIPAOLO, JA TI DOWN-REGULATION OF KERATIN-14 GENE-EXPRESSION AFTER V-HA-RAS TRANSFECTION OF HUMAN PAPILLOMAVIRUS-IMMORTALIZED HUMAN CERVICAL EPITHELIAL-CELLS SO CANCER RESEARCH LA English DT Article ID INTERMEDIATE-SIZED FILAMENTS; UTERINE CERVIX; TYPE-16 DNA; TERMINAL DIFFERENTIATION; HUMAN KERATINOCYTES; MESSENGER-RNAS; GENITAL CANCER; LINES; CYTOKERATINS; CARCINOMA AB Keratin expression in human cervical squamous cell carcinoma (SCC) lines differed significantly from both normal and human papillomavirus (HPV) immortalized exocervical cells. Keratin 14 (K14) expression, determined by protein synthesis and mRNA levels, was dramatically down-regulated in the cervical SCC lines while keratin 5 (K5) expression was not. K14 expression was similarly down-regulated in an HPV-16 immortalized cervical cell line after tumorigenic transformation with recombinant v-Ha-ras DNA. Cultures derived from nude mouse tumor explants also exhibited an altered keratin profile and the levels of K14 protein synthesis, as well as K14 mRNA, were not detectable. In both cases K5 protein synthesis was not significantly down-regulated. In addition, neoplastic cervical SCC lines exhibited up-regulation of keratins 7, 8, 13, and 19, combined with slight down-regulation of keratins 6 and 16. Epidermal keratinocytes responded in a different manner to exocervical cells. Transfection of human papillomavirus-immortalized epidermal keratinocytes with the BglII N fragment of herpes simplex virus 2 produced a neoplastic cell line, but K5 and K14 expression remained unchanged. Thus, neoplastic transformation of human exocervical cells, both in vivo (spontaneous cervical SCC) and in vitro (HPV-16- and v-Ha-ras-induced cervical SCC), is accompanied by characteristic changes in keratin expression. The specific down-regulation of K14 in these tumorigenic cervical cells, in the absence of significant changes in the expression of K5, implies that the normal coordinate regulation of K5 and K14 gene expression has been uncoupled. C1 NCI,DIV CANC ETIOL,BIOL LAB,BETHESDA,MD 20892. NR 54 TC 15 Z9 15 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 NOV 1 PY 1992 VL 52 IS 21 BP 5865 EP 5871 PG 7 WC Oncology SC Oncology GA JV496 UT WOS:A1992JV49600002 PM 1382846 ER PT J AU EVANS, CH BAKER, PD AF EVANS, CH BAKER, PD TI DECREASED P-GLYCOPROTEIN EXPRESSION IN MULTIDRUG-SENSITIVE AND MULTIDRUG-RESISTANT HUMAN MYELOMA CELLS INDUCED BY THE CYTOKINE LEUKOREGULIN SO CANCER RESEARCH LA English DT Article ID MULTIPLE-DRUG RESISTANCE; PLASMA-MEMBRANE; BIOCHEMICAL-CHARACTERIZATION; MONOCLONAL-ANTIBODIES; TUMOR-CELLS; VERAPAMIL; REVERSAL; PERMEABILITY; BINDING; LINES AB Modulation of the expression of P-glycoprotein, a plasma membrane protein associated with multidrug resistance, was examined in drug-sensitive and drug-resistant tumor cells treated with leukoregulin, a M(r) 50,000 cytokine from human lymphocytes that rapidly permeabilizes the plasma membrane of many tumor cells facilitating the uptake of doxorubicin and other tumor-inhibitory antibiotics. P-glycoprotein expression was measured flow cytometrically by the binding of C219 or MRK16 monoclonal antibody to multidrug-sensitive human K562 erythroleukemia and 8226/S myeloma cells, compared to multidrug-resistant 8226/DOX40 Myeloma cells. Cells were treated for up to 2 h with up to 80 units of leukoregulin/ml or one of a variety of unrelated cytokines including interleukin 1alpha (IL-1alpha), IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, colony-stimulating factor, macrophage colony-stimulating factor, granulocyte macrophage colony-stimulating factor, tumor necrosis factor alpha, gamma-interferon, alpha-interferon, epidermal growth factor, platelet-derived growth factor AA, platelet-derived growth factor BB, insulin-like growth factor I, insulin-like growth factor II, fibroblast growth factor, or transforming growth factor beta. Leukoregulin caused a concentration-dependent decrease in P-glycoprotein expression; however, P-glycoprotein expression was unaffected by the other cytokines (<12% decrease in expression). Leukoregulin-induced membrane permeabilization, determined flow cytometrically by intracellular fluorescein efflux, and decreased P-glycoprotein expression occurred simultaneously within 15 min in drug-sensitive and -resistant cells. Enhanced doxorubicin uptake, measured flow cytometrically by doxorubicin influx, was also present within 15 min. Leukoregulin enhancement of doxorubicin uptake and increased membrane permeability varied directly with the decrease in P-glycoprotein expression. Leukoregulin in combination with doxorubicin enhanced the inhibition of cell proliferation in 8226/DOX40 multidrug-resistant cells over expressing P-glycoprotein. In contrast, combined treatment of HL-60/MX2 multidrug-resistant human promyelocytic leukemia cells that do not overexpress P-glycoprotein in association with their multidrug resistance resulted in no greater growth inhibition than observed with HL-60/MX2 cells treated with doxorubicin alone. This is the first demonstration that a naturally occurring macromolecule with anticancer activities can modulate the expression of P-glycoprotein concomitant with enhanced drug uptake and inhibition of cell proliferation. RP EVANS, CH (reprint author), NCI,DIV CANC ETIOL,BIOL LAB,TUMOR BIOL SECT,BLDG 37,ROOM 2A01,BETHESDA,MD 20892, USA. NR 56 TC 21 Z9 22 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1992 VL 52 IS 21 BP 5893 EP 5899 PG 7 WC Oncology SC Oncology GA JV496 UT WOS:A1992JV49600006 PM 1356622 ER PT J AU MULLEN, CA COALE, MM LEVY, AT STETLERSTEVENSON, WG LIOTTA, LA BRANDT, S BLAESE, RM AF MULLEN, CA COALE, MM LEVY, AT STETLERSTEVENSON, WG LIOTTA, LA BRANDT, S BLAESE, RM TI FIBROSARCOMA CELLS TRANSDUCED WITH THE IL-6 GENE EXHIBIT REDUCED TUMORIGENICITY, INCREASED IMMUNOGENICITY, AND DECREASED METASTATIC POTENTIAL SO CANCER RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; TISSUE INHIBITOR; FACTOR-ALPHA; INTERLEUKIN-6; CANCER; EXPRESSION; ANTIGENS; IMMUNITY; MICE AB Murine fibrosarcoma cell lines transduced with retroviral vectors containing the murine interleukin 6 (IL-6) gene constitutively secreted IL-6. When injected s.c. into normal mice these IL-6-secreting tumors exhibited reduced tumorigenicity. This reduced tumorigenicity was not seen in nude or irradiated mice, implicating a T-cell-dependent, radio-sensitive host response activated by the cytokine. Subcutaneous IL-6-secreting tumor did not retard the growth of distant deposits of wild-type tumor in the same host. However, animals rejecting IL-6-secreting tumors exhibited resistance to later challenge with wild-type tumor. When injected i.v. in an experimental metastasis model the IL-6-secreting tumors failed to or were extremely inefficient in giving rise to pulmonary nodules; this was observed in both normal and immunoincompetent mice, implicating a second, nonimmune mechanism affecting the growth of the tumor modified to secrete IL-6. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20892. VANDERBILT UNIV,MED CTR,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,DEPT CELL BIOL,NASHVILLE,TN 37232. RP MULLEN, CA (reprint author), NCI,METAB BRANCH,BLDG 10,ROOM 4N115,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 27 TC 120 Z9 120 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 NOV 1 PY 1992 VL 52 IS 21 BP 6020 EP 6024 PG 5 WC Oncology SC Oncology GA JV496 UT WOS:A1992JV49600024 PM 1394227 ER PT J AU BENNETT, WP HOLLSTEIN, MC METCALF, RA WELSH, JA HE, A ZHU, SM KUSTERS, I RESAU, JH TRUMP, BF LANE, DP HARRIS, CC AF BENNETT, WP HOLLSTEIN, MC METCALF, RA WELSH, JA HE, A ZHU, SM KUSTERS, I RESAU, JH TRUMP, BF LANE, DP HARRIS, CC TI P53 MUTATION AND PROTEIN ACCUMULATION DURING MULTISTAGE HUMAN ESOPHAGEAL CARCINOGENESIS SO CANCER RESEARCH LA English DT Note ID SQUAMOUS-CELL CARCINOMA; BREAST-CANCER; COLORECTAL TUMORIGENESIS; SV40-TRANSFORMED CELLS; AERODIGESTIVE TRACT; TRANSFORMED-CELLS; GENE-MUTATIONS; TUMORS; ANTIGEN; EXPRESSION AB Preinvasive lesions of squamous cell carcinoma are well defined morphologically and provide a model for multistage carcinogenesis. Since alterations in the p53 tumor suppressor gene occur frequently in invasive esophageal squamous cell carcinoma, we examined a set of preinvasive lesions to investigate the timing of p53 mutation. Surgically resected tissues from nine patients with esophageal squamous cell carcinoma contained precursor lesions which had not yet invaded normal tissues. Immunohistochemistry showed high levels of p53 protein in both preinvasive lesions and invasive carcinomas in six cases; sequence analysis of all invasive tumors identified p53 missense mutations in two cases. Preinvasive lesions from both tumors with mutations plus one wild-type tumor were microdissected and sequenced. In one patient there were different mutations in the invasive carcinoma (codon 282, CGG(arg) > TGG(trp)) and a preinvasive lesion (codon 272, GTG(val) > T/GTG(leu/val)). In a second case, an invasive carcinoma had a mutation in codon 175 (CGC(arg) > CAC(his)), and adjacent preinvasive lesions contained a wild-type sequence. A carcinoma and preinvasive lesion from the third case contained high levels of protein and a wild-type DNA sequence. Therefore, p53 mutation may precede invasion in esophageal carcinogenesis, and multifocal esophageal neoplasms may arise from independent clones of transformed cells. The timing of p53 protein accumulation is favorable for an intermediate biomarker in multistage esophageal carcinogenesis. C1 NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C01,BETHESDA,MD 20892. INT AGCY RES CANC,LYON 2,FRANCE. CHINA MED UNIV,CANC RES INST,SHENYANG,PEOPLES R CHINA. SUN YAT SEN UNIV MED SCI,CANTON,PEOPLES R CHINA. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. UNIV DUNDEE,CANC RES CAMPAIGN LAB,DUNDEE DD1 4HN,SCOTLAND. RI Lane, David/C-4920-2008 NR 44 TC 205 Z9 214 U1 0 U2 2 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 NOV 1 PY 1992 VL 52 IS 21 BP 6092 EP 6097 PG 6 WC Oncology SC Oncology GA JV496 UT WOS:A1992JV49600036 PM 1394236 ER PT J AU FURMANSKI, P NEILSON, EG BHORJEE, JS PADARATHSINGH, M AF FURMANSKI, P NEILSON, EG BHORJEE, JS PADARATHSINGH, M TI THE ROLE OF CYTOKINES IN THE REGULATION OF CELL-FUNCTION AND IN THE PATHOGENESIS OF DISEASE - A PATHOLOGY-A PATHOLOGY-B STUDY SECTION WORKSHOP SO CANCER RESEARCH LA English DT Editorial Material C1 NIH,DIV RES GRANTS,BETHESDA,MD 20892. UNIV PENN,SCH MED,DIV RENAL ELECTROLYTE,PHILADELPHIA,PA 19104. NYU,DEPT BIOL,NEW YORK,NY 10003. NR 0 TC 3 Z9 3 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 NOV 1 PY 1992 VL 52 IS 21 BP 6129 EP 6133 PG 5 WC Oncology SC Oncology GA JV496 UT WOS:A1992JV49600045 PM 1394240 ER PT J AU LEDOUX, SP WILSON, GL BEECHAM, EJ STEVNSNER, T WASSERMANN, K BOHR, VA AF LEDOUX, SP WILSON, GL BEECHAM, EJ STEVNSNER, T WASSERMANN, K BOHR, VA TI REPAIR OF MITOCHONDRIAL-DNA AFTER VARIOUS TYPES OF DNA DAMAGE IN CHINESE-HAMSTER OVARY CELLS SO CARCINOGENESIS LA English DT Article ID INTERSTRAND CROSS-LINKS; ALKALI-LABILE SITES; PYRIMIDINE DIMERS; N-NITROSOUREA; NUCLEAR-DNA; RAT-LIVER; MUTATIONS; GENE; GLYCOSYLASE; DISEASE AB Using methodology recently developed to assess gene-specific DNA repair, we have demonstrated that it is possible not only to study mitochondrial DNA repair, but also directly to compare mitochondrial and nuclear DNA repair in the same biological sample. Complex enzymatic mechanisms recognize and repair nuclear DNA damage, but it has long been thought that there was no DNA repair in mitochondria. Therefore, in an attempt to delineate more clearly which DNA repair mechanisms, if any, are functioning in mitochondria, we have investigated the repair of several specific DNA lesions in mitochondrial DNA. They include cyclobutane dimers, cisplatin intrastrand adducts, cisplatin interstrand crosslinks and alkali-labile sites. We find that pyrimidine dimers and complex alkylation damage are not repaired in mitochondrial DNA, and that there is minimal repair of cisplatin intrastrand crosslinks. In contrast, there is efficient repair of cisplatin interstrand crosslinks as evidenced by approximately 70% of the lesions being removed by 24 h. Additionally, there is efficient repair of N-methylpurines following exposure to methylnitrosourea with approximately 70% of the lesions being removed by 24 h. The results of these studies reveal that repair capacity of mitochondrial DNA damage depends upon the type of lesion produced by the damaging agent. We speculate that a process similar to the base excision mechanism for nuclear DNA exists for mitochondrial DNA but that there is no nucleotide excision repair mechanism to remove more bulky lesions in this organelle. C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. UNIV SO ALABAMA,DEPT STRUCT & CELLULAR BIOL,MOBILE,AL 36688. FU NIEHS NIH HHS [ES03456] NR 46 TC 199 Z9 208 U1 0 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1992 VL 13 IS 11 BP 1967 EP 1973 DI 10.1093/carcin/13.11.1967 PG 7 WC Oncology SC Oncology GA JY125 UT WOS:A1992JY12500005 PM 1423864 ER PT J AU LINK, CJ MITCHELL, DL NAIRN, RS BOHR, VA AF LINK, CJ MITCHELL, DL NAIRN, RS BOHR, VA TI PREFERENTIAL AND STRAND-SPECIFIC DNA-REPAIR OF (6-4) PHOTOPRODUCTS DETECTED BY A PHOTOCHEMICAL METHOD IN THE HAMSTER DHFR GENE SO CARCINOGENESIS LA English DT Article ID CYCLOBUTANE PYRIMIDINE DIMERS; DIHYDROFOLATE-REDUCTASE GENE; MAMMALIAN-CELLS; OVARY CELLS; REMOVAL; DAMAGE AB A non-enzymatic method that was previously shown to create single-strand DNA breaks at the location of (6-4) photoproducts in the overall genome was adapted to measure (6-4) photoproducts at the level of the gene. This approach employs a photoisomerization step that converts the (6-4) photoproduct into the Dewar valence photoisomer, which is more alkaline labile and allows for the creation of a single-strand DNA break at this site. These strand breaks were quantified via Southern analysis and the DNA repair of (6-4) photoproducts was measured over 2, 4 and 8 h after a UV dose of 40 J/m2. A comparison of repair efficiency in the actively transcribed dihydrofolate reductase (DHFR) gene, a transcriptionally inactive genomic region and the overall genome (as measured by radioimmunoassay) showed preferential repair of the active gene. The active DHFR gene showed 59% repair by 8 h compared to 33% repair in the inactive downstream region. Analysis of (6-4) photoproduct repair in the transcribed and non-transcribed strands of the DHFR gene indicate some strand specificity with 62% repair in the transcribed strand at 8 h compared with 43% repair in the non-transcribed strand. However, this strand bias is much less distinct than has been reported for the major UV photoproduct, the cyclobutane pyrimidine dimer. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DIV RES,SMITHVILLE,TX 78957. RP LINK, CJ (reprint author), NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 27 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1992 VL 13 IS 11 BP 1975 EP 1980 DI 10.1093/carcin/13.11.1975 PG 6 WC Oncology SC Oncology GA JY125 UT WOS:A1992JY12500006 PM 1423865 ER PT J AU WALKER, MP JAHNKE, GD SNEDEKER, SM GLADEN, BC LUCIER, GW DIAUGUSTINE, RP AF WALKER, MP JAHNKE, GD SNEDEKER, SM GLADEN, BC LUCIER, GW DIAUGUSTINE, RP TI P-32 POSTLABELING ANALYSIS OF THE FORMATION AND PERSISTENCE OF DNA ADDUCTS IN MAMMARY-GLANDS OF PAROUS AND NULLIPAROUS MICE TREATED WITH BENZO[A]PYRENE SO CARCINOGENESIS LA English DT Article ID EPITHELIAL-CELLS; BENZO(A)PYRENE; BINDING; METABOLISM; RAT; CARCINOGENESIS; 7,12-DIMETHYLBENZANTHRACENE; SUSCEPTIBILITY; LYMPHOCYTES; ACTIVATION AB The susceptibility of the rodent mammary gland to known chemical carcinogens can vary with the stage of gland development. Full-term pregnancy (parity) can confer permanent structural and functional changes in the gland that are associated with decreased breast cancer risk in humans and protection from mammary carcinogenesis in rodents. In this study, the formation and persistence of benzo[a]pyrene (B[a]P)-derived DNA adducts in vivo was determined in the abdominal mammary organs of adult nulliparous and parous BALB/c mice treated orally with the carcinogen. Mammary DNA isolated from animals in both groups revealed only one major adduct on TLC maps by P1-nuclease P-32-postlabeling analysis. The major adduct co-migrated with the (+)-enantiomer of anti-BPDE-dGp. Much lower levels of the (-)-enantiomer were detected. Most of the adduct quantitated was probably contributed by cells of the stromal compartment, since the gland-free organ (cleared fat pad) generated essentially equivalent profiles and level of adduct by P-32-postlabeling. Comparable levels of the B[a]P-derived adduct were observed in the intact mammary organ of both nulliparous and parous mice during a time course from 1 to 28 days after treatment. In both cases, adduct removal occurred exponentially with a half-life of approximately 16 days. The capacity for de novo formation of reactive metabolites by the mammary organ was demonstrated in vitro: digests of DNA from mammary mince exposed to B[a]P generated an adduct on TLC maps that also co-migrated with the (+)-anti-BPDE-dGp standard. Thus, our cumulative findings confirm the capacity of mammary cells to form potentially carcinogenic DNA adducts; however, the functional changes that occur in the mouse mammary gland as a result of parity did not influence the profile, level or persistence of adduct following exposure to a known carcinogen. Other factors, such as changes in mammary cell cycle kinetics or responsiveness to promotional stimuli may be more causally related to reduction in incidence of neoplasia observed in parous animals. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP WALKER, MP (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 13 Z9 13 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 NOV PY 1992 VL 13 IS 11 BP 2009 EP 2015 DI 10.1093/carcin/13.11.2009 PG 7 WC Oncology SC Oncology GA JY125 UT WOS:A1992JY12500011 PM 1423869 ER PT J AU ANDERSON, LM CARTER, JP LOGSDON, DL DRIVER, CL KOVATCH, RM AF ANDERSON, LM CARTER, JP LOGSDON, DL DRIVER, CL KOVATCH, RM TI CHARACTERIZATION OF ETHANOLS ENHANCEMENT OF TUMORIGENESIS BY N-NITROSODIMETHYLAMINE IN MICE SO CARCINOGENESIS LA English DT Article ID HUMAN CANCER; METABOLISM; DIMETHYLNITROSAMINE; RAT; DEMETHYLASE; ALCOHOL; LIVER; DISPOSITION; INHIBITION; PIG AB The concentration-, time- and route-dependent effects of ethanol co-administration on tumorigenesis by N-nitrosodimethylamine (NDMA) were characterized in strain A male mice. With drinking-water administration, 1% ethanol was as effective as 5 or 10% in effecting a 4-fold enhancement of lung tumorigenesis by 5 p.p.m. NDMA. In a study of cumulative effects over time, 10% ethanol given with 1 p.p.m. NDMA resulted in a progressive increase in lung tumors from 16 to 72 weeks. In addition, at 72 weeks, the ethanol co-treatment resulted in a significant increase in kidney adenomas and possibly in vascular tumors of liver. A single i.g. dose of 5 mg/kg NDMa was significantly tumorigenic for lung, and the effect was dose-dependently increased by inclusion of ethanol, for up to a 9-fold enhancement with 20% ethanol. When 10% ethanol was given in the drinking water while NDMA was administered as 20 1 mg/kg doses by other routes-i.g., i.p., s.c. or i.v.-the ethanol treatment was without effect on lung tumor numbers. Collectively, the results provide strong support for inhibition of hepatic first-pass clearance of NDMA by cytochrome P450 2E1 as the mechanism of ethanol's effect, and suggest that several other possible mechanisms are unlikely. They also illustrate that a moderate dose of ethanol cumulatively increases tumor risk from a low dose of NDMA given over most of the lifetime of the animal. C1 PATHOL ASSOCIATES INC,FREDERICK,MD 21701. RP ANDERSON, LM (reprint author), PRI-DYN CORP,NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 28 TC 27 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1992 VL 13 IS 11 BP 2107 EP 2111 DI 10.1093/carcin/13.11.2107 PG 5 WC Oncology SC Oncology GA JY125 UT WOS:A1992JY12500026 PM 1423883 ER PT J AU HENNINGS, H LOWRY, DT ROBINSON, VA MORGAN, DL FUJIKI, H YUSPA, SH AF HENNINGS, H LOWRY, DT ROBINSON, VA MORGAN, DL FUJIKI, H YUSPA, SH TI ACTIVITY OF DIVERSE TUMOR PROMOTERS IN A KERATINOCYTE COCULTURE MODEL OF INITIATED EPIDERMIS SO CARCINOGENESIS LA English DT Article ID MOUSE SKIN CARCINOGENESIS; JUNCTIONAL INTERCELLULAR COMMUNICATION; PROTEIN-KINASE; OKADAIC ACID; CELL COMMUNICATION; TRANSFORMED PHENOTYPE; PHORBOL ESTERS; DIFFERENTIATION; THAPSIGARGIN; INHIBITION AB The suppression of focal growth of initiated mouse keratinocytes by co-culture with normal keratinocytes can be overcome by treatment of co-cultures with the phorbol ester tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA). This keratinocyte co-culture model was developed as an analog of initiated mouse epidermis to facilitate the study of tumor promotion in cell culture. A number of promoters of TPA-type [those with protein kinase C (PKC) as receptor] were compared to non-TPA-type promoters for activity in the keratinocyte co-culture model. The TPA-type promoters teleocidin and aplysiatoxin show comparable activity to that of TPA. Exposure of co-cultures to oleoyl-2-acetylglycerol, a diacylglycerol activator of PKC, also induces focal outgrowth of initiated cells, suggesting that PKC is likely to be involved in the mechanism of action of these compounds. However, the involvement of alternative pathways (not involving PKC directly) for clonal selection are evident since the non-TPA-type promoters okadaic acid, staurosporine and thapsigargin are also active in the assay. Thus, the keratinocyte co-culture model differs from fibroblast models of normal and neoplastic co-cultures in which only TPA-type promoters are active. In further contrast to certain fibroblast co-cultures, TPA does not inhibit cell - cell communication under conditions that suppress focus formation. Taken together with previous data, we conclude that the keratinocyte co-culture model may have broad application for detecting skin tumor promoters, and may be useful for dissecting the mechanism by which normal epidermal cells suppress the growth of initiated cells. C1 NATL CANC CTR,RES INST,DIV CANC PREVENT,TOKYO 104,JAPAN. RP HENNINGS, H (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892, USA. NR 43 TC 24 Z9 25 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 NOV PY 1992 VL 13 IS 11 BP 2145 EP 2151 DI 10.1093/carcin/13.11.2145 PG 7 WC Oncology SC Oncology GA JY125 UT WOS:A1992JY12500033 PM 1423887 ER PT J AU SZALLASI, Z KRAUSZ, KW BLUMBERG, PM AF SZALLASI, Z KRAUSZ, KW BLUMBERG, PM TI NONPROMOTING 12-DEOXYPHORBOL 13-ESTERS AS POTENT INHIBITORS OF PHORBOL 12-MYRISTATE 13-ACETATE-INDUCED ACUTE AND CHRONIC BIOLOGICAL RESPONSES IN CD-1 MOUSE SKIN SO CARCINOGENESIS LA English DT Article ID PROTEIN-KINASE-C; ORNITHINE DECARBOXYLASE INDUCTION; CULTURED HUMAN KERATINOCYTES; TUMOR PROMOTION; BENZOYL PEROXIDE; POLYMORPHONUCLEAR LEUKOCYTES; CELL-PROLIFERATION; MYRISTATE ACETATE; GENE-EXPRESSION; ESTER AB In previous experiments, pretreatment of CD-1 mouse skin with prostratin (12-deoxyphorbol 13-acetate) inhibited hyperplasia, induction of ornithine decarboxylase and edema in response to acute treatment with phorbol 12-myristate 13-acetate (PMA). We report here that prostratin inhibits biological responses induced by multiple (chronic) PMA treatment. A typical chronic treatment schedule consisted of rive applications of 3.2 nmol (2 mug) PMA at 48 h intervals. Most effective inhibition could be achieved when the first PMA treatment was preceded 48 h before by a lower dose of prostratin (256 nmol = 100 mug) and each PMA treatment was preceded 15 min before by a higher dose (2.56 mumol = 1 mg) of prostratin. Under this schedule hyperplasia was completely blocked, as was keratin K6 expression (a marker of hyperproliferative epidermis), whereas myeloperoxidase activity (a marker of neutrophil granulocyte infiltration) was reduced to 36%. 12-Deoxyphorbol 13-phenylacetate (dPP), a non-promoting 12-deoxyphorbol derivative that binds to protein kinase C with two orders of magnitude higher potency than does prostratin, showed the same pattern of inhibition as did prostratin for a single PMA treatment but with a corresponding two orders of magnitude higher potency. In the case of chronic PMA treatment, however, dPP failed to inhibit hyperplasia fully, though it reduced keratin K6 expression and inflammation. Dissociation of K6 expression from hyperplasia was unexpected, since expression of these two responses was thought to be closely coupled. We conclude that 12-deoxyphorbol 13-monoesters are functional antagonists for a class of protein kinase C-mediated responses closely correlated to tumor promotion. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 51 TC 24 Z9 24 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 1992 VL 13 IS 11 BP 2161 EP 2167 DI 10.1093/carcin/13.11.2161 PG 7 WC Oncology SC Oncology GA JY125 UT WOS:A1992JY12500035 PM 1385002 ER PT J AU BATOVA, A DANIELPOUR, D PIRISI, L CREEK, KE AF BATOVA, A DANIELPOUR, D PIRISI, L CREEK, KE TI RETINOIC ACID INDUCES SECRETION OF LATENT TRANSFORMING GROWTH FACTOR-BETA-1 AND FACTOR-BETA-2 IN NORMAL AND HUMAN PAPILLOMAVIRUS TYPE 16-IMMORTALIZED HUMAN KERATINOCYTES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID BREAST-CANCER-CELLS; FACTOR-BETA; GENE-EXPRESSION; DIFFERENTIAL REGULATION; MOUSE KERATINOCYTES; EPITHELIAL-CELLS; MESSENGER-RNA; RECEPTOR; INHIBITION; PROMOTER AB Similar cellular responses are elicited by retinoic acid (RA) and transforming growth factor beta (TGF-beta). We investigated the ability of RA to modulate the production of TGF-beta in normal human keratinocytes (HKc) and HKc lines immortalized by transfection with human papillomavirus type 16 DNA (HKc/HPV16). RA treatment of both normal HKc and HKc/HPV16 resulted in a 2-3-fold induction in secreted levels of latent TGF-beta. The induction in TGF-beta secretion by RA was dose dependent, with significant increases observed with RA concentrations as low as 1-10 nm, and time dependent, with maximal induction occurring about 3 days after initiation of RA exposure. In addition, RA induced intracellular levels of TGF-beta almost 5-fold. Sandwich enzyme-linked immunosorbent assays were used to specifically quantify TGF-beta1, and TGF-beta2 secreted by normal HKc and HKc/HPV16 cultured in the absence or presence of RA. RA increased the secreted levels of latent TGF-beta1, and TGF-beta2 an average of 2- and 5-fold, respectively, with no major differences in the fold induction between normal HKc and HKc/HPV16. Northern blot analysis of mRNA isolated from HKc/HPV16 demonstrated that RA treatment induced specific transcripts for TGF-beta1 and TGF-beta2, about 3- and 50-fold, respectively. RA treatment of HKc had no significant effect on the binding affinity of TGF-beta for its receptors or receptor number. Normal HKc and HKc/HPV16 displayed similar dose-dependent inhibition of proliferation by TGF-beta1. These studies indicate that RA may regulate growth control in both normal HKc and HKc/HPV16 by enhancing TGF-beta1 and TGF-beta2 production, which, after activation at the cell surface, could inhibit cellular proliferation in an autocrine and/or paracrine manner. C1 UNIV S CAROLINA,DEPT CHEM & BIOCHEM,PHYS SCI BLDG,COLUMBIA,SC 29208. UNIV S CAROLINA,SCH MED,DEPT PATHOL,COLUMBIA,SC 29208. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [R29CA48990]; NCRR NIH HHS [S07 RR07160] NR 66 TC 37 Z9 38 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD NOV PY 1992 VL 3 IS 11 BP 763 EP 772 PG 10 WC Cell Biology SC Cell Biology GA JY281 UT WOS:A1992JY28100002 PM 1334692 ER PT J AU GRIESEMER, RA AF GRIESEMER, RA TI DOSE SELECTION FOR ANIMAL CARCINOGENICITY STUDIES - A PRACTITIONERS PERSPECTIVE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID N-NITROSODIMETHYLAMINE; CHRONIC INGESTION; NITROSODIETHYLAMINE; EXPOSURE; RATS RP GRIESEMER, RA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 13 TC 8 Z9 8 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 NOV-DEC PY 1992 VL 5 IS 6 BP 737 EP 741 DI 10.1021/tx00030a001 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KB009 UT WOS:A1992KB00900002 PM 1489921 ER PT J AU COHEN, SM ELLWEIN, LB AF COHEN, SM ELLWEIN, LB TI RISK ASSESSMENT BASED ON HIGH-DOSE ANIMAL EXPOSURE EXPERIMENTS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CHEMICAL CARCINOGENESIS; URINARY-BLADDER; MALE-RAT; CANCER; TOXICITY; SACCHARIN; MUTATION; MODEL C1 NEI,BETHESDA,MD 20892. UNIV NEBRASKA,MED CTR,EPPLEY INST CANC RES,OMAHA,NE 68198. RP COHEN, SM (reprint author), UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,600 S 42ND ST,OMAHA,NE 68198, USA. NR 50 TC 37 Z9 37 U1 0 U2 2 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 NOV-DEC PY 1992 VL 5 IS 6 BP 742 EP 748 DI 10.1021/tx00030a002 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KB009 UT WOS:A1992KB00900003 PM 1489922 ER PT J AU POIRIER, MC BELAND, FA AF POIRIER, MC BELAND, FA TI DNA ADDUCT MEASUREMENTS AND TUMOR-INCIDENCE DURING CHRONIC CARCINOGEN EXPOSURE IN ANIMAL-MODELS - IMPLICATIONS FOR DNA ADDUCT-BASED HUMAN CANCER RISK ASSESSMENT SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID DOSE-RESPONSE RELATIONSHIP; MOLECULAR DOSIMETRY; CHEMICAL CARCINOGENESIS; RAT-LIVER; BLADDER; 2-ACETYLAMINOFLUORENE; AFLATOXIN-B1; 4-(N-METHYL-N-NITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; DIETHYLNITROSAMINE; INDUCTION C1 NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. RP POIRIER, MC (reprint author), NCI,DIV CANC ETIOL,BLDG 37,ROOM 3B25,BETHESDA,MD 20892, USA. NR 38 TC 156 Z9 157 U1 2 U2 4 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 NOV-DEC PY 1992 VL 5 IS 6 BP 749 EP 755 DI 10.1021/tx00030a003 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KB009 UT WOS:A1992KB00900004 PM 1489923 ER PT J AU KASPRZAK, KS DIWAN, BA RICE, JM MISRA, M RIGGS, CW OLINSKI, R DIZDAROGLU, M AF KASPRZAK, KS DIWAN, BA RICE, JM MISRA, M RIGGS, CW OLINSKI, R DIZDAROGLU, M TI NICKEL(II)-MEDIATED OXIDATIVE DNA-BASE DAMAGE IN RENAL AND HEPATIC CHROMATIN OF PREGNANT RATS AND THEIR FETUSES - POSSIBLE RELEVANCE TO CARCINOGENESIS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SITE-SPECIFIC MUTAGENESIS; IONIZING-RADIATION; HYDROGEN-PEROXIDE; BARBITURIC-ACID; THYMINE GLYCOL; F344 RATS; NICKEL; SODIUM; RADICALS; KIDNEY AB DNA base damage was studied in renal and hepatic chromatin of nickel(II)-injected pregnant female F344/NCr rats and their fetuses under conditions leading to initiation of sodium barbital-promotable renal tumors, but not liver tumors, in the male offspring. Pregnant rats were given a total of 90 or 180 mumol of nickel(II) acetate/kg body wt in a single ip dose on day 17 or in 2 or 4 ip doses between days 12 and 18 of gestation. Control rats received 180 mumol of sodium acetate/kg body wt. The animals were killed 24 or 48 h after the last injection. Chromatin was isolated from livers and kidneys from both adults and fetuses and analyzed by gas chromatography/mass spectrometry with selected ion monitoring. Eleven products derived from the purine and pyrimidine bases in DNA bases were identified and quantified. These were the following: 5-hydroxy-5-methylhydantoin,5-hydroxyhydantoin,5-(hydroxymethyl)uracil,cytosine glycol, thymine glycol, 5,6-dihydroxycytosine, 4,6-diamino-5-formamidopyrimidine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine,8-hydroxyadenine, 2-hydroxyadenine, and 8-hydroxyguanine (8-OH-Gua). Nickel(II) exposure increased the content of these products, especially those derived from purines, in both renal and hepatic chromatin of pregnant rats. The major difference between these two organs was the content of 8-OH-Gua, which increased greatly in the kidney but remained unchanged in the liver. In the corresponding fetal organs, the relative increases in 8-OH-Gua were comparable to the findings in adults. Fetal kidney DNA was relatively higher in pyrimidine-derived products (especially thymine glycol and 5-hydroxyhydantoin) and lower in purine-derived products (except for 8-OH-Gua) than fetal hepatic DNA. No consistent dose effect of nickel(II) on the amounts of the DNA base products recovered from either organ was observed in either the dams or their fetuses. The products determined were typical hydroxyl radical-produced derivatives of DNA bases, suggesting a role for hydroxyl radical in the induction of their formation by nickel(II). Some of these base products have been shown previously to be promutagenic. Therefore, the present results indicate possible involvement of oxidative DNA base damage in the mechanism of nickel(II) carcinogenesis in the rat kidney. The prevalence of 8-OH-Gua in the kidney but not in the liver is consistent with the hypothesis that 8-OH-Gua is a tumor-initiating lesion in that organ. However, the complexity of the observed response to nickel(II) does not exclude possible roles for other DNA base products elevated by nickel(II) treatment, especially thymine glycol and 5-hydroxyhydantoin, in nickel(II)-induced carcinogenesis in the kidney. C1 NCI,DYNCORP,PROGRAM RESOURCES INC,FCRDC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. NCI,DATA MANAGEMENT SERV INC,FCRDC,FREDERICK,MD 21702. NATL INST STAND & TECHNOL,CHEM SCI & TECHNOL LAB,GAITHERSBURG,MD 20899. RP KASPRZAK, KS (reprint author), NCI,FCRDC,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. RI Olinski, Ryszard/E-9607-2014 FU NCI NIH HHS [N01-CO-74102] NR 46 TC 75 Z9 75 U1 0 U2 4 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 NOV-DEC PY 1992 VL 5 IS 6 BP 809 EP 815 DI 10.1021/tx00030a013 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KB009 UT WOS:A1992KB00900014 PM 1489933 ER PT J AU SNYDERWINE, EG WELTI, DH FAY, LB WURZNER, HP TURESKY, RJ AF SNYDERWINE, EG WELTI, DH FAY, LB WURZNER, HP TURESKY, RJ TI METABOLISM OF THE FOOD MUTAGEN 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE IN NONHUMAN-PRIMATES UNDERGOING CARCINOGEN BIOASSAY SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID NORMAL INTESTINAL BACTERIA; HUMAN-LIVER; SALMONELLA-TYPHIMURIUM; HETEROCYCLIC AMINES; RAT; ACTIVATION; DNA; IQ; IDENTIFICATION; ARYLAMINES AB 2-Amino-3-methylimidazo[4.5-f]quinoline (IQ) is a potent bacterial mutagen and rodent carcinogen which also produces hepatocellular carcinoma in monkeys. The metabolism and disposition of this procarcinogen were investigated in monkeys undergoing carcinogen bioassay and in monkeys given an acute dose of IQ. Analysis of urine, feces, and bile revealed that IQ was extensively metabolized. A number of metabolites in urine were purified by high-performance liquid chromatography and characterized by H-1 NMR and mass spectroscopy. Metabolites resulted from cytochrome P450-mediated ring oxidation at the C-5 position or N-demethylation. These metabolites could be further transformed by conjugation to sulfate or beta-glucuronic acid. Glucuronidation and sulfamate formation at the exocyclic amine group were other major routes of metabolism. Enteric bacteria also contributed to IQ biotransformation by forming the 7-oxo derivatives of IQ and N-demethyl-IQ. The metastable N2-glucuronide conjugate of the carcinogenic metabolite, 2-(hydroxyamino)-3-methylimidazo[4,5-f] quinoline, was found in urine. This indicates that metabolic activation through cytochrome P450-mediated N-oxidation occurs in vivo and that glucuronidation is a means of transport of the carcinogenic metabolite to extrahepatic tissues. C1 NESTEC LTD,NESTLE RES CTR,CH-1000 LAUSANNE 26,SWITZERLAND. RP SNYDERWINE, EG (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-51013] NR 45 TC 29 Z9 29 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 NOV-DEC PY 1992 VL 5 IS 6 BP 843 EP 851 DI 10.1021/tx00030a018 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA KB009 UT WOS:A1992KB00900019 PM 1489936 ER PT J AU MCINTOSH, CL MARON, BJ CANNON, RO KLUES, HG AF MCINTOSH, CL MARON, BJ CANNON, RO KLUES, HG TI INITIAL RESULTS OF COMBINED ANTERIOR MITRAL LEAFLET PLICATION AND VENTRICULAR SEPTAL MYOTOMY-MYECTOMY FOR RELIEF OF LEFT-VENTRICULAR OUTFLOW TRACT OBSTRUCTION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Article DE MITRAL VALVE; SURGERY; ECHOCARDIOGRAPHY ID SUB-AORTIC STENOSIS; TERM FOLLOW-UP; SUBAORTIC STENOSIS; VALVE REPLACEMENT; SURGICAL-TREATMENT; CLINICAL MANIFESTATIONS; OPERATIVE TREATMENT; SYMPTOMATIC STATUS; PATHO-PHYSIOLOGY; THERAPY AB Background. Several operations (most commonly ventricular septal myotomy-myectomy and also mitral valve replacement) have been performed to relieve symptoms and obstruction to left ventricular outflow in patients with hypertrophic cardiomyopathy (HCM). Methods and Results. In an effort to establish an alternative to mitral valve replacement, combined septal myotomy-myectomy and suture plication of the anterior mitral valve leaflet was performed in a subgroup of 36 severely symptomatic patients with obstructive HCM. These patients were selected primarily because the mitral leaflets were judged morphologically at the time of operation to be of sufficient size relative to that of the outflow tract to represent a risk for residual systolic septal contact and outflow obstruction. The effects of operation were assessed in 34 patients; of the 33 with preoperative symptoms, 28 (85%) reported substantial functional improvement after surgery over an average follow-up of 2.2 years. Of 29 patients with complete hemodynamic data, basal outflow gradient was obliterated or reduced substantially by surgery (to less-than-or-equal-to 35 mm Hg) in 26 patients (90%) and for the group from 81+/-2 to 16+/-24 mm Hg (p < 0.001); provocable gradient with isoproterenol infusion also decreased considerably (from 109+/-50 to 47+/-25 mm Hg; p < 0.001). Echocardiographic studies showed that plication limited the systolic anterior motion of anterior mitral leaflet. There was no hemodynamic evidence of mitral stenosis, and in only one patient did mitral regurgitation increase after surgery. Conclusions. Mitral valve plication combined with myotomy-myectomy in obstructive HCM 1) can be performed safely and does not adversely alter mitral valve function, 2) relieves symptoms and outflow obstruction under basal and provocable conditions, and 3) may represent an alternative to mitral valve replacement in selected patients with elongated and enlarged mitral leaflets. C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. NR 43 TC 64 Z9 64 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1992 VL 86 IS 5 SU S BP 60 EP 67 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JX589 UT WOS:A1992JX58900008 ER PT J AU LACROIX, AZ YANO, K REED, DM AF LACROIX, AZ YANO, K REED, DM TI DEHYDROEPIANDROSTERONE SULFATE, INCIDENCE OF MYOCARDIAL-INFARCTION, AND EXTENT OF ATHEROSCLEROSIS IN MEN SO CIRCULATION LA English DT Article DE CORONARY HEART DISEASE; ATHEROSCLEROSIS; AGING; CORONARY ARTERY DISEASE; DEHYDROEPIANDROSTERONE SULFATE; MYOCARDIAL INFARCTION ID CORONARY HEART-DISEASE; PLASMA DEHYDROEPIANDROSTERONE; LIFESTYLE CHARACTERISTICS; SEX-DIFFERENCES; HONOLULU; DIETARY; PROGRAM; HAWAII; RABBIT; JAPAN AB Background. Antiatherogenic effects of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) have been suspected for more than 30 years, yet the available evidence to support or refute such effects in humans is inconclusive. The hypothesis has not been adequately tested in large-scale epidemiological studies. Methods and Results. The present study used a cohort of men initially free of clinically detectable coronary heart disease, stroke, and cancer to compare DHEAS levels measured in sera obtained in 1968-1971 between 238 cases who had definite coronary heart disease during the subsequent 18 years and 476 age-matched controls who survived the follow-up period and remained free of clinically detectable coronary heart disease. In a separate study, the relation of DHEAS levels to extent of atherosclerosis was examined among 82 cohort men who died during the follow-up period and had protocol autopsies. Age-adjusted DHEAS levels were lower among fatal cases of coronary heart disease than among controls (94.7 versus 106.9 mug/dl, respectively; p<0.05). After adjustment for eight coronary risk factors, the odds ratio for fatal coronary heart disease comparing a 100-mug/dl difference in DHEAS level was 0.46 (95% confidence intervals, 0.19-1.07). In contrast, age-adjusted DHEAS levels did not significantly differ between nonfatal cases of myocardial infarction and controls (107.2 versus 106.9 mug/dl, respectively). Furthermore, DHEAS levels were not related to extent of atherosclerosis at autopsy. Conclusions. These findings do not support a role of DHEAS in the development of nonfatal myocardial infarction or the progression of atherosclerosis. The association of DHEAS with fatal coronary heart disease and possibly with death from all causes merits further investigation. These findings suggest continued skepticism that DHEAS has an important role in coronary disease etiology or prevention. C1 KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. NIH,HONOLULU,HI. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. RP LACROIX, AZ (reprint author), GRP HLTH COOP PUGET SOUND,CTR HLTH STUDIES,1730 MINOR AVE,SUITE 1600,SEATTLE,WA 98101, USA. FU NHLBI NIH HHS [N01-HV-02901] NR 32 TC 103 Z9 103 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 NOV PY 1992 VL 86 IS 5 BP 1529 EP 1535 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JW981 UT WOS:A1992JW98100023 PM 1423966 ER PT J AU GIMPLE, LW GERTZ, SD HABER, HL RAGOSTA, M POWERS, ER ROBERTS, WC SAREMBOCK, IJ AF GIMPLE, LW GERTZ, SD HABER, HL RAGOSTA, M POWERS, ER ROBERTS, WC SAREMBOCK, IJ TI EFFECT OF CHRONIC SUBCUTANEOUS OR INTRAMURAL ADMINISTRATION OF HEPARIN ON FEMORAL-ARTERY RESTENOSIS AFTER BALLOON ANGIOPLASTY IN HYPERCHOLESTEROLEMIC RABBITS - A QUANTITATIVE ANGIOGRAPHIC AND HISTOPATHOLOGICAL STUDY SO CIRCULATION LA English DT Article DE RESTENOSIS; ANGIOPLASTY; HEPARIN; BALLOONS ID LUMINAL CORONARY ANGIOPLASTY; MUSCLE CELL-PROLIFERATION; SMOOTH-MUSCLE; ATHEROSCLEROTIC RABBIT; INTIMAL HYPERPLASIA; THROMBIN; INHIBITION; INJURY; DETERMINANTS; PREVENTION AB Background. Heparin is known to have antithrombotic, anticoagulant, and antiproliferative effects. We hypothesized that chronic subcutaneous and/or direct intramural administration of heparin would reduce restenosis and inhibit plaque growth after balloon angioplasty. Methods and Results. Focal atherosclerosis was induced bilaterally in the femoral arteries of 59 rabbits by air desiccation intimal injury and a 2% cholesterol diet. After angioplasty, the rabbits were assigned to one of four treatment groups. Control arteries (n = 21) received no additional heparin. A second group of 20 arteries was treated with a porous balloon that delivered heparin (1,500 units) directly into the arterial wall. A third group (n = 29) received subcutaneous heparin (350 units . kg-1 . day-1) for 28 days, and a fourth group (n = 23) was treated with subcutaneous and intramural heparin. Quantitative angiography showed a modest reduction in restenosis (defined as the change in minimal luminal diameter from immediately after angioplasty to 28 days) with subcutaneous heparin compared with control arteries (0.32+/-0.18 versus 0.58+/-0.34 mm, p<0.01); however, luminal diameter was not improved at 28 days compared with before angioplasty. Intramural delivery of heparin by the porous balloon catheter was confirmed by use of fluoresceinated heparin in one animal. Angiographic restenosis was not reduced in arteries treated with intramural heparin versus controls (0.61+/-0.54 versus 0.58+/-0.34 mm, p = NS). Blinded planimetric analysis of histological sections showed no differences in luminal cross-sectional area narrowing by atherosclerotic plaque, in plaque area, or in plaque/media ratio at 28 days among the four treatment groups. Conclusions. Chronic subcutaneous heparin after balloon angioplasty results in a modest reduction in angiographic restenosis in this model; however, the absolute luminal diameter is not improved compared with before angioplasty, and plaque area and percent luminal narrowing by plaque were not different among the four treatment groups. Heparin can be delivered into an atherosclerotic plaque by a porous balloon, but this treatment does not reduce restenosis after angioplasty in this model. C1 UNIV VIRGINIA,HLTH SCI CTR,DIV CARDIOL,BOX 158,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT MED,CHARLOTTESVILLE,VA 22908. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,IL-91010 JERUSALEM,ISRAEL. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 31 TC 53 Z9 54 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 NOV PY 1992 VL 86 IS 5 BP 1536 EP 1546 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JW981 UT WOS:A1992JW98100024 PM 1423967 ER PT J AU KOZIOL, DE HENDERSON, DK AF KOZIOL, DE HENDERSON, DK TI OBSTACLES TO HIV PREVENTION SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Editorial Material RP KOZIOL, DE (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD NOV-DEC PY 1992 VL 59 IS 6 BP 647 EP 648 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JY066 UT WOS:A1992JY06600024 PM 1424078 ER PT J AU THOMPSON, HL MATSUSHIMA, K AF THOMPSON, HL MATSUSHIMA, K TI HUMAN POLYMORPHONUCLEAR LEUKOCYTES STIMULATED BY TUMOR-NECROSIS-FACTOR-ALPHA SHOW INCREASED ADHERENCE TO EXTRACELLULAR-MATRIX PROTEINS WHICH IS MEDIATED VIA THE CD11B 18 COMPLEX SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE POLYMORPHONUCLEAR LEUKOCYTES; ADHESION; TUMOR NECROSIS FACTOR; INTEGRINS ID HUMAN VASCULAR ENDOTHELIUM; HUMAN NEUTROPHIL ADHERENCE; LEUKOCYTE ADHESION; MONOCLONAL-ANTIBODIES; INTERLEUKIN-1; RECEPTOR; MECHANISMS; INVITRO; ANTIGEN; MAC-1 AB The present study demonstrates that tumour necrosis factor (TNF) and FMLP, but not IL-1 or IL-8, enhanced the adherence of polymorphonuclear neutrophil (PMN) to fibronectin, an extracellular matrix protein. The adherence induced by FMLP was very rapid, within 5 min while the induction of adherence by TNF was much slower, reaching maximum at 60 min. TNF also enhanced an adhesion of PMN to other extracellular matrix proteins, such as laminin, collagen IV and gelatin II, but not to human serum albumin. Anti-CD18 MoAb completely inhibited the binding of TNF-stimulated PMN to fibronectin and partially inhibited the binding to laminin. Further investigation showed that adhesion of TNF-stimulated PMN to fibronectin and laminin was inhibited by anti-CD11b MoAb and to a lesser extent by CD11a MoAb. In contrast to TNF-stimulated PMN the binding of unstimulated PMN to fibronectin and laminin was only inhibited by anti-CD11a MoAb. Anti-CD11c had no effect on PMN adherence. These results suggest that unstimulated PMN adhere to extracellular proteins through the CD11a/18, while TNF-stimulated PMN adhere through the CD11b/18. These results suggest that TN F secreted at the site of inflammation may enhance the interaction of PMN with the extravascular environment through the CD11b/18 complex. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21701. RP THOMPSON, HL (reprint author), STRANGEWAYS RES LAB,CYTOKINE BIOCHEM,WORTS CAUSEWAY,CAMBRIDGE CB1 4RN,ENGLAND. NR 47 TC 41 Z9 41 U1 2 U2 3 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 NOV PY 1992 VL 90 IS 2 BP 280 EP 285 PG 6 WC Immunology SC Immunology GA JV654 UT WOS:A1992JV65400022 PM 1358490 ER PT J AU EGWUAGU, CE BAHMANYAR, S MAHDI, RM NUSSENBLATT, RB GERY, I CASPI, RR AF EGWUAGU, CE BAHMANYAR, S MAHDI, RM NUSSENBLATT, RB GERY, I CASPI, RR TI PREDOMINANT USAGE OF V-BETA-8.3 T-CELL RECEPTOR IN A T-CELL LINE THAT INDUCES EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU) SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID RETINOID-BINDING-PROTEIN; MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; BETA-CHAIN USAGE; V-GENE USAGE; S-ANTIGEN; RAT; IDENTIFICATION; IRBP; IMMUNODOMINANT RP EGWUAGU, CE (reprint author), NEI,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 49 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD NOV PY 1992 VL 65 IS 2 BP 152 EP 160 DI 10.1016/0090-1229(92)90218-D PG 9 WC Immunology; Pathology SC Immunology; Pathology GA JU440 UT WOS:A1992JU44000009 PM 1382911 ER PT J AU GERBERDING, JL HENDERSON, DK AF GERBERDING, JL HENDERSON, DK TI USE OF ZIDOVUDINE FOLLOWING OCCUPATIONAL EXPOSURE TO HUMAN-IMMUNODEFICIENCY-VIRUS - REPLY SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NIH,WARREN G MAGNUSEN CLIN CTR,BETHESDA,MD 20892. RP GERBERDING, JL (reprint author), SAN FRANCISCO GEN HOSP,MED SERV 5H-22,1001 POTRERO AVE,SAN FRANCISCO,CA 94110, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1992 VL 15 IS 5 BP 885 EP 885 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JX339 UT WOS:A1992JX33900024 ER PT J AU HUGHES, WT PIZZO, PA WADE, JC ARMSTRONG, D WEBB, CD YOUNG, LS AF HUGHES, WT PIZZO, PA WADE, JC ARMSTRONG, D WEBB, CD YOUNG, LS TI EVALUATION OF NEW ANTIINFECTIVE DRUGS FOR THE TREATMENT OF FEBRILE EPISODES IN NEUTROPENIC PATIENTS SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB The use of empirical antimicrobial therapy has significantly reduced the morbidity and mortality associated with untreated infections in febrile neutropenic patients. This guideline describes clinical trials of the safety and efficacy of new antimicrobial drugs in this population of patients. Fever and neutropenia should be precisely defined in each protocol. Patients should be randomized to treatment with a new or active-control drug regimen, stratified on the basis of type of cancer and age, and treated until resolution-as defined in the protocol-is attained. Outcome should be assessed both for cases with a defined microbial etiology and for those without. Final microbiological outcome is important for cases with identified pathogens, but clinical outcome is paramount. C1 NCI, BETHESDA, MD 20892 USA. UNIV MARYLAND, CTR CANC, BALTIMORE, MD 21201 USA. MEM SLOAN KETTERING CANC HOSP, NEW YORK, NY USA. KUZELL INST, SAN FRANCISCO, CA USA. PFIZER PHARMACEUT INC, NEW YORK, NY USA. RP HUGHES, WT (reprint author), ST JUDE CHILDRENS RES HOSP, DIV INFECT DIS, 332 N LAUDERDALE, MEMPHIS, TN 38105 USA. FU AHRQ HHS [HHS 223-88-1301] NR 4 TC 48 Z9 49 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1992 VL 15 SU 1 BP S206 EP S215 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JX586 UT WOS:A1992JX58600027 PM 1477232 ER PT J AU GEORGE, DT LINDQUIST, T RAWLINGS, RR ECKARDT, MJ MOSS, H MATHIS, C MARTIN, PR LINNOILA, M AF GEORGE, DT LINDQUIST, T RAWLINGS, RR ECKARDT, MJ MOSS, H MATHIS, C MARTIN, PR LINNOILA, M TI PHARMACOLOGICAL MAINTENANCE OF ABSTINENCE IN PATIENTS WITH ALCOHOLISM - NO EFFICACY OF 5-HYDROXYTRYPTOPHAN OR LEVODOPA SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; ELECTROCHEMICAL DETECTION; CEREBROSPINAL-FLUID; WITHDRAWAL SYNDROME; LITHIUM-CARBONATE; ETHANOL INTAKE; DOUBLE-BLIND; SEROTONIN; DEPENDENCE; DOPAMINE AB Pharmacologic enhancement of central nervous system serotonin and dopamine functions has been postulated to improve maintenance of abstinence in patients with alcoholism. To test this hypothesis, patients with alcoholism who completed a 42-day inpatient treatment program were randomized to be administered, in a double-blind fashion, either 5-hydroxytryptophan and carbidopa, levodopa and carbidopa, or placebo for 1 year. Eight of 31 patients who entered the analysis remained abstinent from alcohol for 1 year; however, there was no significant effect of the treatment condition on maintenance of abstinence. Baseline psychologic measures showed that patients who abstained from alcohol had more education and higher scores on memory function tests. Measures of cerebrospinal fluid obtained before the start of the study indicated that all patients who had higher concentrations of the dopamine metabolite homovanillic acid relapsed, suggesting that further research is needed to elucidate the role of dopamine in alcoholism. C1 HAHNEMANN UNIV,SCH MED,PHILADELPHIA,PA 19102. UNIV PITTSBURGH,SCH MED,WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15261. VANDERBILT UNIV,MED CTR,SCH MED,DEPT PSYCHIAT,NASHVILLE,TN 37232. RP GEORGE, DT (reprint author), NIAAA,CLIN SCI SECT,9000 ROCKVILLE PIKE BLDG,10 ROOM 3B19,BETHESDA,MD 20892, USA. RI Martin, Peter/A-7738-2008 NR 53 TC 25 Z9 25 U1 2 U2 2 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 NOV PY 1992 VL 52 IS 5 BP 553 EP 560 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KA748 UT WOS:A1992KA74800015 PM 1424429 ER PT J AU SHINOHARA, T KIKUCHI, T TSUDA, M YAMAKI, K AF SHINOHARA, T KIKUCHI, T TSUDA, M YAMAKI, K TI A FAMILY OF RETINAL S-ANTIGENS (ARRESTINS) AND THEIR GENES - COMPARATIVE-ANALYSIS OF HUMAN, MOUSE, RAT, BOVINE AND DROSOPHILA SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Review ID BETA-ADRENERGIC-RECEPTOR; 48-KDA PROTEIN; PINEAL-GLAND; 5'-FLANKING SEQUENCES; RHODOPSIN-KINASE; EXPRESSION; CDNA; PHOTORECEPTOR; ORGANIZATION; MEMBRANES RP SHINOHARA, T (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892, USA. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 32 TC 9 Z9 9 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 NOV PY 1992 VL 103 IS 3 BP 505 EP 509 DI 10.1016/0305-0491(92)90361-T PG 5 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA JX537 UT WOS:A1992JX53700001 PM 1458825 ER PT J AU MUNOZ, MD OSHEAALVAREZ, MD PEREZGARCIA, J WEINBACH, EC MORENO, MA DELATORRE, M MAGOS, MA TOVAR, R AF MUNOZ, MD OSHEAALVAREZ, MD PEREZGARCIA, J WEINBACH, EC MORENO, MA DELATORRE, M MAGOS, MA TOVAR, R TI PURIFICATION AND BIOCHEMICAL-PROPERTIES OF CALMODULIN IN ENTAMOEBA-HISTOLYTICA AND ITS DISTRIBUTION DURING SECRETION OF ELECTRON-DENSE GRANULES SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article ID BINDING PROTEIN; CALCIUM; IDENTIFICATION; ACTIVATION; RECEPTOR; CELLS AB 1. Calmodulin (CaM) was detected during secretion of electron-dense granules by Entamoeba histolytica trophozoites with immunofluorescence. 2. It was purified to apparent homogeneity by chromatography with a yield of 2.26 mug of calmodulin/mg of protozoan protein. Purity was established by gel electrophoresis. 3. The parasite calmodulin has properties characteristic of calmodulin isolated from other eukaryotes: an apparent molecular weight of 19 or 17 kDa in presence of EGTA or CaCl2, respectively, activation in a calcium dependent manner of bovine heart cyclic nucleotide phosphodiesterase, and its UV spectrum. C1 HOSP ESPECIALIDADES CTR MED LA RAZA,INST MEXICANO SEGURO SOCIAL,MEXICO CITY 06760,DF,MEXICO. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP MUNOZ, MD (reprint author), INST POLITECN NACL,CTR INVEST & ESTUDIOS AVANZADOS,DEPT GENET & MOLEC BIOL,MEXICO CITY 07300,DF,MEXICO. NR 28 TC 24 Z9 24 U1 0 U2 1 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 NOV PY 1992 VL 103 IS 3 BP 517 EP 521 DI 10.1016/0305-0491(92)90363-V PG 5 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA JX537 UT WOS:A1992JX53700003 PM 1458827 ER PT J AU COGAN, DG KRUTH, HS DATILIS, MB MARTIN, N AF COGAN, DG KRUTH, HS DATILIS, MB MARTIN, N TI CORNEAL OPACITY IN LCAT DISEASE SO CORNEA LA English DT Article DE LECITHIN CHOLESTEROL ACYLTRANSFERASE DEFICIENCY; PROGRESSIVE CORNEAL OPACITY; DYSLIPOPROTEINEMIA; GLARE EFFECT; ANEMIA; RENAL DISEASE; UNESTERIFIED CHOLESTEROL IN TISSUE; FREE LECITHIN IN TISSUE AB Deficiency of lecithin:cholesterol acyltransferase, LCAT disease, is one of the dyslipoproteinemias with characteristic lipid deposits in the cornea. The present report documents the clinicopathologic abnormalities of one case in which a full-thickness corneal specimen was obtained at the time of corneal transplantation. The characteristic clinical abnormality was a progressive corneal opacification with a peripheral arcus that extended into the sclera. The pathologic abnormality consisted of vacuoles prevalent in the anterior corneal stroma by light microscopy and containing extracellular, membranous deposits by electron microscopy. These observations confirm and supplement the previous six pathologic reports of corneal changes in LCAT disease and demonstrate, for the first time, histopathologic evidence of unesterified cholesterol in the corneal stroma of LCAT disease. RP COGAN, DG (reprint author), NEI,CORNEA & CATARACT SECT,BLDG 10,ROOM 6C401,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 1992 VL 11 IS 6 BP 595 EP 599 DI 10.1097/00003226-199211000-00021 PG 5 WC Ophthalmology SC Ophthalmology GA JU431 UT WOS:A1992JU43100021 PM 1468226 ER PT J AU EINHORN, PT RIFKIND, BM AF EINHORN, PT RIFKIND, BM TI REGRESSION OF CORONARY ATHEROSCLEROSIS SO CORONARY ARTERY DISEASE LA English DT Editorial Material C1 NHLBI,DIV HEART & VASC DIS,LIPID METAB ATHEROGENESIS BRANCH,ROOM 401,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD NOV PY 1992 VL 3 IS 11 BP 1105 EP 1107 DI 10.1097/00019501-199211000-00014 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JV664 UT WOS:A1992JV66400014 ER PT J AU ZAHNWAXLER, C EMDE, RN ROBINSON, JL AF ZAHNWAXLER, C EMDE, RN ROBINSON, JL TI THE DEVELOPMENT OF EMPATHY IN TWINS SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID INDIVIDUAL-DIFFERENCES; DISTRESS; RESPONSES; HERITABILITY; PERSPECTIVE; ALTRUISM; OTHERS; FAMILY AB This study examined empathy in 94 monozygotic (MZ) and 90 dizygotic (DZ) twin pairs during the 2nd year of life. Children's reactions to simulations of distress in others were videotaped in home and laboratory settings. Some components of concern for others increased with age between 14 and 20 months for both MZ and DZ twins. Girls scored higher than boys on most of these observational measures. The different components (eg., emotional concern, prosocial acts, and cognitive exploration) showed substantial coherence and low but significant stability over time. There was modest evidence for heritability of empathy, particularly for the affective component. Maternal reports of prosocial orientations indicated both genetic and environmental influences. C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. UNIV COLORADO,INST BEHAV GENET,BOULDER,CO 80309. RP ZAHNWAXLER, C (reprint author), NIMH,DEPT HLTH & HUMAN SERV,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 192 Z9 193 U1 1 U2 37 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD NOV PY 1992 VL 28 IS 6 BP 1038 EP 1047 DI 10.1037//0012-1649.28.6.1038 PG 10 WC Psychology, Developmental SC Psychology GA JY321 UT WOS:A1992JY32100007 ER PT J AU HIGLEY, JD THOMPSON, WW HOPKINS, WD BYRNE, EA HIRSCH, RM SUOMI, SJ AF HIGLEY, JD THOMPSON, WW HOPKINS, WD BYRNE, EA HIRSCH, RM SUOMI, SJ TI PEERS AS PRIMARY ATTACHMENT SOURCES IN YEARLING RHESUS-MONKEYS (MACACA-MULATTA) SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID SOCIAL RECOVERY; YOUNG-CHILDREN; 1ST YEAR; REHABILITATION; BEHAVIOR; BLANKETS; OBJECTS; MOTHERS; AGENTS; LIFE AB Peer bonds were examined in 2 experiments using juvenile rhesus monkeys to determine (a) whether specific attachment bonds are formed between age-mates, (b) whether preferred age-mates can provide a secure base, and (c) whether a previous attachment bond affects the quality of subsequent attachment bonds. In Experiment 1, 8 peer-only reared (PO) monkeys demonstrated a specific preference for a predicted favorite peer when given a choice between a familiar and 2 unfamiliar peers. In Experiment 2, PO Ss were placed in a novel setting with either their most preferred peer, a familiar but not preferred peer, or an unfamiliar peer, and their responses were compared with those of a 2nd group of monkeys, reared for their first 6 months of life by their mother. Both mother-reared (MP) and PO monkeys displayed significantly more intimate contact and significantly less distress when with their most preferred peer; nevertheless, even when they were with their most preferred peer, PO Ss exhibited more distress than MP Ss. Findings are discussed with reference to current attachment theory. C1 NATL INST ALCOHOL ABUSE & ALCOHOLISM,CLIN STUDIES LAB,BETHESDA,MD. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. GEORGIA STATE UNIV,ATLANTA,GA 30303. UNIV MARYLAND,INST CHILD STUDY,COLL PK,MD 20742. NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. NR 36 TC 17 Z9 17 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD NOV PY 1992 VL 28 IS 6 BP 1163 EP 1171 DI 10.1037/0012-1649.28.6.1163 PG 9 WC Psychology, Developmental SC Psychology GA JY321 UT WOS:A1992JY32100019 ER PT J AU SIEVERS, ML NELSON, RG KNOWLER, WC BENNETT, PH AF SIEVERS, ML NELSON, RG KNOWLER, WC BENNETT, PH TI IMPACT OF NIDDM ON MORTALITY AND CAUSES OF DEATH IN PIMA-INDIANS SO DIABETES CARE LA English DT Article ID ISCHEMIC-HEART-DISEASE; DEPENDENT DIABETES-MELLITUS; NATIONAL SAMPLE; GLUCOSE LEVELS; UNITED-STATES; FOLLOW-UP; PREVALENCE; POPULATION; ACCURACY; CERTIFICATE AB OBJECTIVE - To compare overall and cause-specific death rates for diabetic and nondiabetic Pima Indians. RESEARCH DESIGN AND METHODS- This community-based study determined overall and cause-specific death rates in persons with and without NIDDM in the Pima population. Underlying causes of death for the 10-yr period from 1975 to 1984 were derived from review of death certificates and medical records. Diabetes diagnoses were based on an ongoing diabetes study initiated by die National Institutes of Health in 1965. RESULTS - Of the 512 deaths, 241 were in Pima Indians with NIDDM; 203 (84%) of the deaths in diabetic subjects were attributed to natural causes (46 diabetic nephropathy, 35 IHD, 29 infections, 20 malignant neoplasms, 20 alcoholic liver disease, 18 stroke, 35 other causes). For natural causes, the overall age-sex-adjusted death rate in diabetic subjects was 1.7 times (95% CI 1.4-2.2) that in nondiabetic subjects. Longer duration of diabetes was significantly related to mortality, an association that was stronger in women than in men. Rates of death from diabetic nephropathy, IHD, and infections (but not stroke) were each significantly related to longer diabetes duration. Together, diabetic nephropathy and IHD accounted for 90% of the excess death rate among diabetic, compared with nondiabetic, Pimas. CONCLUSIONS- In Pima Indians, NIDDM has a significant adverse effect on death rates that is directly related to diabetes duration, especially for deaths from diabetic nephropathy, IHD, or infections. Among the Pima, diabetic nephropathy is the leading cause of death, and IHD ranks second-a variation from other populations (in which IHD ranks first), probably partly attributable to a much younger age of onset of diabetes among the Pima than in the U.S. white population. C1 CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,PHOENIX,AZ. RP SIEVERS, ML (reprint author), NATL INST DIABETES & DIGEST & KIDNEY DIS,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ 85014, USA. RI Nelson, Robert/B-1470-2012 NR 49 TC 61 Z9 61 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1992 VL 15 IS 11 BP 1541 EP 1549 DI 10.2337/diacare.15.11.1541 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JW614 UT WOS:A1992JW61400018 PM 1468284 ER PT J AU THURM, U HARPER, PN AF THURM, U HARPER, PN TI IM RUNNING ON INSULIN - SUMMARY OF THE HISTORY OF THE INTERNATIONAL-DIABETIC-ATHLETES-ASSOCIATION SO DIABETES CARE LA English DT Article; Proceedings Paper CT 1990 SYMP ON DIABETES AND EXERCISE CY MAY 19-21, 1990 CL DUSSELDORF, GERMANY SP BAYER AB The changes that physical activity brings in the functioning of the human body have a special interest to active individuals with diabetes. Certain adjustments in dosing are necessary. Even today, with such an emphasis on healthy life-style, little information is available to assist an individual with diabetes to exercise safely Granted, no easy formula exists. Many different factors influence blood glucose. Most often, individuals with diabetes learn by trial and error how to best manage their favorite activity. In 1985, Paula Harper founded the International Diabetic Athletes Association (IDAA) in hopes of educating people with diabetes about the benefits of regular exercise. For most individuals with insulin-dependent (type I) diabetes mellitus, it is not encouragement, but safety that is the issue. The IDAA offers great opportunities for sharing ideas at its annual meetings. These meetings attract an exceptional faculty of speakers and offer a mix of workshops led by experienced diabetic athletes on various sports. A quarterly newsletter is published that presents new information and recognizes success stories. IDDA chapters exist in the U.S., Canada, U.K., Germany, France, Luxembourg, Switzerland, Belgium, the Netherlands, and Spain. C1 UNIV DUSSELDORF,DEPT NUTR & METAB,W-4000 DUSSELDORF 1,GERMANY. RP THURM, U (reprint author), NIH,MEDLANT RES FDN,BLDG 1,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. NR 0 TC 5 Z9 7 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1992 VL 15 IS 11 BP 1811 EP 1813 DI 10.2337/diacare.15.11.1811 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JW614 UT WOS:A1992JW61400055 PM 1468319 ER PT J AU LAZOWSKI, KW MERTZ, PM REDMAN, RS ANN, DK KOUSVELARI, E AF LAZOWSKI, KW MERTZ, PM REDMAN, RS ANN, DK KOUSVELARI, E TI RECIPROCAL EXPRESSION OF C-JUN, PROLINE-RICH PROTEIN AND AMYLASE GENES DURING RAT PAROTID SALIVARY-GLAND DEVELOPMENT SO DIFFERENTIATION LA English DT Article ID ALPHA-AMYLASE; GROWTH-FACTORS; ACINAR-CELLS; 2 PROMOTERS; MOUSE; FOS; DIFFERENTIATION; TRANSCRIPTION; STIMULATION; INDUCTION AB We have investigated the temporal expression and cellular localization of the c-jun proto-oncogene and two major rat parotid gland secretory protein genes, PRP (proline-rich protein) and amylase, during postnatal development. c-jun mRNA steady-state levels increased at days 1, 7 and 14 after birth and decreased to basal levels at 21 days and older. PRP mRNA was first detected at 14 days and abruptly increased to adult levels at day 21. Amylase transcripts were first seen at day 7 and progressively increased to adult levels by 28 days. In situ hybridization demonstrated c-jun mRNA accumulation in the differentiating acinar cells and the ducts. The c-jun mRNA accumulation with time corresponds with the proliferative activity reported to occur in these two cellular populations. PRP transcripts were present exclusively in the well differentiated acinar cells while the accumulation of amylase mRNA corresponded to the progressive commitment of parotid cells to acinar differentiation. Our data suggest that during the postnatal development of the rat parotid gland: (a) c-jun expression associates with parotid gland proliferation and precedes the expression of PRP and amylase genes, and (b) activation of PRP and amylase genes is not concomitant and apparently occurs only in differentiating acinar cells. C1 DEPT VET AFFAIRS MED CTR,ORAL PATHOL RES LAB,WASHINGTON,DC 20422. UNIV MINNESOTA,SCH MED,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. RP KOUSVELARI, E (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1A-19,BETHESDA,MD 20892, USA. NR 30 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD NOV PY 1992 VL 51 IS 3 BP 225 EP 232 DI 10.1111/j.1432-0436.1992.tb00700.x PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA JV636 UT WOS:A1992JV63600010 PM 1281129 ER PT J AU MILLER, MJ MAHER, VM MCCORMICK, JJ AF MILLER, MJ MAHER, VM MCCORMICK, JJ TI QUANTITATIVE 2-DIMENSIONAL GEL-ELECTROPHORESIS ANALYSIS OF HUMAN FIBROBLASTS TRANSFORMED BY RAS ONCOGENES SO ELECTROPHORESIS LA English DT Article ID LIVER EPITHELIAL-CELLS; MALIGNANT TRANSFORMATION; TUMOR PROGRESSION; N-RAS; V-RAF; EXPRESSION; PROTEINS; MODEL AB Quantitative two-dimensional gel electrophoresis was used to compare the cellular protein patterns of a normal foreskin-derived human fibroblast cell line (LG1) and three immortal derivatives of LG1. One derivative, designated MSU-1.1 VO, was selected for its ability to grow in the absence of serum and is non-tumorigenic in athymic mice. The other two strains were selected for focus-formation following transfection with either Ha-ras or N-ras oncogenes and form high grade malignant tumors. Correspondence and cluster analysis provided a nonbiased estimate of the relative similarity of the different two-dimensional patterns. These techniques separated the gel patterns into three distinct classes: LG1, MSU-1.1 VO, and the ras-transformed cell strains. The MSU-1.1 VO cells were more closely related to the parental LG1 than to the ras-transformed cells. The differences between the three classes were primarily quantitative in nature: 16 % of the spots demonstrated statistically significant changes (P < 0.01, T test, mean ratio of intensity > 2) in the rate of incorporation of radioactive amino acids. The patterns from the two ras-transformed cell strains were similar, and variations in the expression of proteins that occurred between the separate experiments obscured consistent differences between the Ha-ras and N-ras transformed cells. However, while only 9 out of 758 spots were classified as different (1 %), correspondence analysis could consistently separate the two ras transformants. One of these spots was five times more intense in the Ha-ras transformed cells than the N-ras. These results demonstrate the potential of automated two-dimensional gel analysis for classifying different gel patterns, even patterns whose differences are obscured by the minor changes in spot intensity that arise between separate cell cultures. C1 MICHIGAN STATE UNIV,DEPT MICROBIOL,CARCINOGENESIS LAB,E LANSING,MI 48824. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. RP MILLER, MJ (reprint author), NCI,DCE,LEC,BLDG 37,RM 3C-28,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA21289]; NIEHS NIH HHS [ES65152]; PHS HHS [A611026] NR 29 TC 3 Z9 3 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD NOV PY 1992 VL 13 IS 11 BP 862 EP 870 DI 10.1002/elps.11501301188 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA KD832 UT WOS:A1992KD83200009 PM 1483428 ER PT J AU DIFIORE, PP HELIN, K KRAUS, MH PIERCE, JH ARTRIP, J SEGATTO, O BOTTARO, DP AF DIFIORE, PP HELIN, K KRAUS, MH PIERCE, JH ARTRIP, J SEGATTO, O BOTTARO, DP TI A SINGLE AMINO-ACID SUBSTITUTION IS SUFFICIENT TO MODIFY THE MITOGENIC PROPERTIES OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR TO RESEMBLE THAT OF GP185(ERBB-2) SO EMBO JOURNAL LA English DT Article DE EGFR; ERBB-2; SUBSTRATES; SIGNAL TRANSDUCTION; TYROSINE KINASES ID TYROSINE KINASE-ACTIVITY; EGF-RECEPTOR; SIGNAL TRANSDUCTION; CELLS; PHOSPHORYLATION; PROTEIN; ERBB-2; THREONINE; GENE; SPECIFICITY AB The epidermal growth factor (EGF) receptor (EGFR) and the erbB-2 gene product, gp185erbB-2, exhibit distinct abilities to stimulate mitogenesis in different target cells. By using chimeric molecules between these two receptors, we have previously shown that their intracellular juxta-membrane regions are responsible for this specificity. Here we describe a genetically engineered EGFR mutant containing a threonine for arginine substitution at position 662 in the EGFR juxtamembrane domain, corresponding to threonine 694 in gp185erbB-2. This mutant, designated EGFR(Thr662), displayed affinity for EGF binding and catalytic properties that were indistinguishable from those of the wild type EGFR. However, EGFR(Thr662) behaved much as gp185erbB-2 in a number of bioassays which readily distinguish between the mitogenic effects of EGFR and gp185erbB-2. Moreover, significant differences were detected in the pattern of intracellular proteins phosphorylated on tyrosine in vivo by EGFR and EGFR(Thr662) in response to EGF. Thus, small differences in the primary sequence of two closely related receptors have dramatic effects on their ability to couple with mitogenic pathways. C1 REGINA ELENA INST CANC RES,I-00158 ROME,ITALY. RP DIFIORE, PP (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010; Di Fiore, Pier Paolo/K-2130-2012 OI Bottaro, Donald/0000-0002-5057-5334; Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 26 TC 31 Z9 31 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV PY 1992 VL 11 IS 11 BP 3927 EP 3933 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JT328 UT WOS:A1992JT32800015 PM 1356764 ER PT J AU CEN, H PAPAGEORGE, AG ZIPPEL, R LOWY, DR ZHANG, K AF CEN, H PAPAGEORGE, AG ZIPPEL, R LOWY, DR ZHANG, K TI ISOLATION OF MULTIPLE MOUSE CDNAS WITH CODING HOMOLOGY TO SACCHAROMYCES-CEREVISIAE CDC25 - IDENTIFICATION OF A REGION RELATED TO BCR, VAV, DBL AND CDC24 SO EMBO JOURNAL LA English DT Article DE CDC24; CDC25; CDC25(MM); RAS; SACCHAROMYCES-CEREVISIAE ID GUANINE-NUCLEOTIDE EXCHANGE; NEUROFIBROMATOSIS TYPE-1 GENE; ACUTE LYMPHOBLASTIC-LEUKEMIA; GTPASE-ACTIVATING PROTEIN; MYOSIN HEAVY-CHAIN; RAS PROTEINS; SEQUENCE; PRODUCT; P21RAS; REGULATORS AB In Saccharomyces cerevisiae, the product of the CDC25 gene is an essential Ras activator that appears to function by stimulating guanine nucleotide exchange on Ras. Using the ability of a mouse cDNA expression library to complement yeast cells lacking functional CDC25, Martegani et al. have identified a 1.7 kb partial cDNA from a gene, designated CDC25Mm, with homology to CDC25. We have now screened a mouse brain cDNA library to identify full-length clones of CDC25Mm. This cloning has led to the isolation of six distinct full-length cDNAs, each of which appear to be derived from the CDC25Mm gene, since their 3' 2 kb appear to be identical and to encode the same 661 C-terminal amino acids. Three cDNAs are predicted to encode protein products of 666 or 667 amino acids. The other three cDNAs encode products that are 836, 1120 and 1260 amino acids, respectively. A 241 amino acid region near the N-terminus of the two largest products was found to have homology to a domain shared by Bcr, Vav, Dbl and CDC24. Polyclonal antibodies raised to a peptide encoded by all the cDNAs have identified at least two protein products in NIH3T3 fibroblasts. Their apparent molecular weights are 75 and 95 kDa, which correspond closely to those predicted to be encoded, respectively, by the two shorter classes of cDNAs. In NIH3T3, the 95 kDa form is much more abundant than the 75 kDa form, while PC-12 pheochromocytoma cells contain relatively high levels of the 75 kDa form. We conclude that CDC25Mm is a complex gene whose protein products are regulated in a tissue-specific manner. C1 UNIV MILAN,DIPARTIMENTO FISIOL & BIOCHIM GEN,SEZ BIOCHIM COMPARATA,I-20122 MILAN,ITALY. RP CEN, H (reprint author), NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892, USA. NR 39 TC 119 Z9 121 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV PY 1992 VL 11 IS 11 BP 4007 EP 4015 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JT328 UT WOS:A1992JT32800023 PM 1396590 ER PT J AU APLAN, PD NAKAHARA, K ORKIN, SH KIRSCH, IR AF APLAN, PD NAKAHARA, K ORKIN, SH KIRSCH, IR TI THE SCL GENE-PRODUCT - A POSITIVE REGULATOR OF ERYTHROID-DIFFERENTIATION SO EMBO JOURNAL LA English DT Article DE BHLH PROTEIN; ERYTHROID DIFFERENTIATION; SCL; TRANSCRIPTION FACTOR ID TRANSCRIPTION FACTOR GATA-1; T-CELL LEUKEMIA; DNA-BINDING PROTEINS; MAMMALIAN-CELLS; MYC PROTEINS; EXPRESSION; ERYTHROLEUKEMIA; LINE; ACTIVATION; MYOD AB The SCL (tal-1, TCL5) gene is a member of the basic domain, helix-loop-helix (bHLH) class of putative transcription factors. We found that (i) the SCL promoter for exon la contains a potential recognition site for GATA-binding transcription factors, (ii) SCL mRNA is expressed in all erythroid tissues and cell lines examined, and (iii) SCL mRNA increases upon induced differentiation of murine erythroleukemia (MEL) cells, and inferred that SCL may play a physiologic role in erythroid differentiation. We used gel shift and transfection assays to demonstrate that the GATA motif in the SCL promoter binds GATA-1 (and GATA-2), and also mediates transcriptional transactivation. To identify a role for SCL in erythroid differentiation, we generated stable transfectants of MEL and K562 (a human chronic myelogenous leukemia cell line that can differentiate along the erythroid pathway) cells overexpressing wild-type, antisense or mutant SCL cDNA. Increasing the level of SCL expression in two independent MEL lines (F4-6 and C19, a 745 derivative) and K562 cells increased the rate of spontaneous (i.e. in the absence of inducer) erythroid differentiation. Conversely, induced differentiation was inhibited in MEL transfectants expressing either antisense SCL cDNA or a mutant SCL lacking the basic domain. Our experiments suggest that the SCL gene can be a target for the erythroid transcription factor GATA-1 and that the SCL gene product serves as a positive regulator of erythroid differentiation. C1 NATL NAVAL MED CTR, NCI NAVY MED ONCOL BRANCH, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NCI, PEDIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. HARVARD UNIV, CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST, DEPT PEDIAT,DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. RI Aplan, Peter/K-9064-2016 NR 40 TC 226 Z9 228 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV PY 1992 VL 11 IS 11 BP 4073 EP 4081 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JT328 UT WOS:A1992JT32800029 PM 1396592 ER PT J AU WINOKUR, PL MCBRIDE, AA AF WINOKUR, PL MCBRIDE, AA TI SEPARATION OF THE TRANSCRIPTIONAL ACTIVATION AND REPLICATION FUNCTIONS OF THE BOVINE PAPILLOMAVIRUS-1 E2-PROTEIN SO EMBO JOURNAL LA English DT Article DE DNA REPLICATION; PAPILLOMAVIRUS; TRANSCRIPTIONAL ACTIVATION ID CARBOXY-TERMINAL DOMAIN; HIGH-COPY-NUMBER; E2 GENE-PRODUCT; DNA-REPLICATION; TRANS-ACTIVATION; BINDING PHOSPHOPROTEIN; TRANSFORMED CELLS; MOUSE CELLS; T-ANTIGEN; TYPE-1 AB Replication of bovine papillomavirus-1 (BPV-1) DNA requires two viral gene products, the El protein and the full-length E2 protein. The 48 kDa E2 protein is a site-specific DNA-binding protein that binds to several sites which lie adjacent to the BPV-1 origin of replication. The 85 amino acid C-terminal domain contains the specific DNA binding and dimerization properties of the protein. The approximately 200 amino acid N-terminal domain is crucial for transcriptional activation. Both of these domains are highly conserved among different papillomaviruses. An internal hinge region separates the two functional domains. The region varies in amino acid sequence and length among the E2 proteins of different papillomaviruses. A series of mutations were constructed within the E2 open reading frame which delete various regions of the conserved DNA binding and transactivation domains as well as the internal hinge region. Two mutated E2 proteins that lack portions of the conserved DNA-binding domain but which support DNA replication were identified using transient replication assays. These mutated E2 proteins were unable to function as transcriptional activators. Conversely, two E2 proteins containing large deletions of the hinge region were able to activate transcription, but were defective for replication. Thus, the replication and transactivation functions of the E2 protein are separable. C1 NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. OI McBride, Alison/0000-0001-5607-5157 NR 49 TC 57 Z9 57 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV PY 1992 VL 11 IS 11 BP 4111 EP 4118 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JT328 UT WOS:A1992JT32800033 PM 1327758 ER PT J AU LEE, CS OKA, T AF LEE, CS OKA, T TI PROGESTERONE REGULATION OF A PREGNANCY-SPECIFIC TRANSCRIPTION REPRESSOR TO BETA-CASEIN GENE PROMOTER IN MOUSE MAMMARY-GLAND SO ENDOCRINOLOGY LA English DT Article ID STEROID-RECEPTOR SUPERFAMILY; CONSERVED SEQUENCE; EXPRESSION; MECHANISMS; PROLACTIN; PROTEIN; CELLS; INDUCTION AB Progesterone inhibits casein gene expression in the mammary gland during pregnancy. A pregnancy-specific mammary nuclear factor (PMF) is a transcriptional repressor that binds to the two separate sites of the beta-casein promoter region and mediates the inhibition of mouse beta-casein gene expression by progesterone. PMF has been detected in mouse mammary tissue during pregnancy, but not during the virginal or lactational periods. Southwestern hybridization showed that the PMF-binding sequence (TGAT/ATCA) bound a protein with a mol wt of 65 kilodaltons from mammary nuclear extract from pregnant mice, but not that from lactating animals. In this study the hormonal regulation of binding activity of PMF and its relationship to casein gene expression were also examined in vivo using ovariectomy of pregnant mice. Ovariectomy rapidly reduces the circulating progesterone and estrogen levels and induces lactogenesis in the mammary tissue of pregnant mice. After ovariectomy, the binding activity of PMF in the mammary gland was reduced to a very low level (<5% of the sham-operated level) at 24 h, whereas the binding activity of another nuclear protein, octamer-like binding factor, was not altered 24 h after the operation. Progesterone injection at the time of ovariectomy inhibited the loss of PMF-binding activity, and the level of its activity was maintained at about 66% the level of sham-operated pregnant animals 24 h after steroid administration. The ability of progesterone to prevent the ovariectomy-mediated decrease in PMF-binding activity was specific, since other steroid hormones, such as estrogen, hydrocortisone, or testosterone, were incapable of doing so. In contrast to PMF, ovariectomy increased the level of beta-casein mRNA in mammary tissue, and this increase was inhibited by concomitant administration of progesterone, suggesting that the extent of beta-casein gene expression was inversely related to PMF-binding activity in mammary tissue. These results are consistent with the view that PMF plays a role in the regulation of casein gene expression by mediating the inhibitory action of progesterone. C1 NATL INST DIABET & DIGEST & KIDNEY DIS,MOLEC & CELLULAR BIOL LAB,BLDG 8,ROOM 304,BETHESDA,MD 20892. NR 33 TC 24 Z9 24 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1992 VL 131 IS 5 BP 2257 EP 2262 DI 10.1210/en.131.5.2257 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JW338 UT WOS:A1992JW33800035 PM 1425425 ER PT J AU WALTHER, MM KRAGEL, PJ TRAHAN, E VENZON, D BLAIR, HC SCHLESINGER, PH JAMAIDOW, C EWING, MW MYERS, CE LINEHAN, WM AF WALTHER, MM KRAGEL, PJ TRAHAN, E VENZON, D BLAIR, HC SCHLESINGER, PH JAMAIDOW, C EWING, MW MYERS, CE LINEHAN, WM TI SURAMIN INHIBITS BONE-RESORPTION AND REDUCES OSTEOBLAST NUMBER IN A NEONATAL MOUSE CALVARIAL BONE-RESORPTION ASSAY SO ENDOCRINOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; PROSTATIC-CANCER CELLS; PARATHYROID-HORMONE; NUDE-MICE; RESORBING BONE; INVITRO; LINE; ADENOCARCINOMA; HYPERCALCEMIA; OSTEOCLASTS AB The antineoplastic properties of suramin, a polyanionic agent with demonstrated antigrowth factor activity, are under evaluation in vitro, in vivo, and in clinical trials. Suramin has been shown to have antitumor activity in patients with advanced, hormone refractory prostate cancer. During these trials, significant resolution of osseous pain was observed in nearly three quarters of the patients treated with suramin. To evaluate the effect of suramin on bone cells, we studied the effect of suramin on bone resorption in a neonatal mouse calvarial assay. Suramin inhibited bone-resorbing activity in a dose-related fashion and had an additive effect with calcitonin. Calvaria pretreated with suramin had less bone-resorbing activity, fewer attached osteoblasts, and less medium alkaline phosphatase activity than control calvaria. Suramin also inhibited osteoclastic release of tritiated proline from labeled bone in a dose-dependent fashion. The effect of metastatic prostate carcinoma on bone is incompletely understood, but may be moderated by tumor-produced factors and/or cytokines. The effects of several such agents, therefore, were examined in combination with suramin. Bone resorption induced by PTH, epidermal growth factor, tumor necrosis factor, and a tumor-produced factor, PTH related-protein, was blocked by suramin. The ability of suramin to inhibit the bone-resorbing effects of several cytokines suggests that its mechanism may involve direct action on bone metabolism. Autoradiography performed on calvaria treated with labeled suramin demonstrated heavy deposition of suramin on the outer surface of the matrix, adjacent to osteoblasts and osteoclasts lining the outer table, suggesting that bone cells may be subject to high local concentrations of the drug, in keeping with this hypothesis. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,BIOCHEM SECT,BETHESDA,MD 20892. NCI,DATA MANAGEMENT SECT,BETHESDA,MD 20892. UNIV MISSOURI,TRUMAN MED CTR,DEPT PATHOL,KANSAS CITY,MO 64108. UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35233. WASHINGTON UNIV,JEWISH HOSP ST LOUIS,SCH DENT MED,MED CTR,DEPT PATHOL,ST LOUIS,MO 63110. RP WALTHER, MM (reprint author), NCI,UROL ONCOL SECT,SURG BRANCH,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008; Schlesinger, Paul/C-6049-2012 NR 39 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1992 VL 131 IS 5 BP 2263 EP 2270 DI 10.1210/en.131.5.2263 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JW338 UT WOS:A1992JW33800036 PM 1425426 ER PT J AU JOHNSON, MC AGUILERA, G AF JOHNSON, MC AGUILERA, G TI STUDIES ON THE MECHANISM OF THE NOVEL STIMULATORY EFFECT OF ANGIOTENSIN-II ON ADENYLATE-CYCLASE IN RAT FETAL SKIN FIBROBLASTS SO ENDOCRINOLOGY LA English DT Article ID PROTEIN KINASE-C; NUCLEOTIDE REGULATORY PROTEIN; BETA-ADRENERGIC-RECEPTOR; ADP-RIBOSYLATION FACTORS; PHORBOL ESTER; CYCLIC-AMP; BINDING-PROTEINS; CHOLERA-TOXIN; CATALYTIC ACTIVITY; PERTUSSIS TOXIN AB In contrast to other systems in which angiotensin-II (AII) inhibits adenylyl cyclase, in fetal skin fibroblasts the peptide stimulates cAMP accumulation. The mechanism of this novel effect was studied by analysis of the actions of AII and other regulators on the adenylyl cyclase system in cultured cells. In the presence of phosphodiesterase inhibitors, AII, isoproterenol (ISO), choleratoxin (CTx), and forskolin (Fk) stimulated cAMP accumulation by 2.0 +/- 0.26-, 26 +/- 0.9-, 75 +/- 5.6-, and 88 +/- 3.3-fold, respectively. All potentiated the stimulatory effect of ISO and CTx by 1.5 +/- 0.1- and 1.25 +/- 0.03-fold, respectively, but had no effect on that of Fk. Preincubation of the cells with PTx did not prevent the stimulatory effect of AII on basal and ISO- and CTx-stimulated cAMP, indicating that the effect of AII was not due to interaction with G(i). Unexpectedly, pretreatment of the cells with PTx for 18 h inhibited cAMP production stimulated by ISO and Fk. Similar inhibition by PTx was observed in adult rat skin fibroblasts, but not in adult human fibroblasts, in which pretreatment with PTx resulted in potentiation of Fk-stimulated cAMP production. ADP ribosylation studies showed that the optical density of the band corresponding to G(s) was less than 20% that of G(i) and G(o) in rat fetal cells, suggesting that excess release of the beta-gamma-subunit is responsible for the inhibition of cAMP production by PTx. However, immunoblot analysis of G-proteins showed that the content of G(s)alpha was similar to that of G(i)alpha and G(o)alpha in rat and human, fetal and adult cells. In contrast to the effect in intact cells, AII had no effect on basal or stimulated adenylyl cyclase activity in cell homogenates, suggesting that the stimulatory effect observed in intact cells is indirect. The stimulatory action of AII on cAMP production was not blocked by indomethacin, indicating that the effect is not mediated by prostaglandin formation. The stimulation of cAMP by AII was mimicked by 10-min incubation with phorbol 12-myristate 13-acetate (PMA), and prevented after cellular protein kinase-C (PKC) depletion by 4- or 6-h preincubation with PMA. However, the stimulation was not prevented by the PKC inhibitors staurosporine and H7 or 24-h preincubation with PMA, suggesting that the effect is not mediated by a traditional PKC-dependent mechanism. This study shows that the synergistic effect of AII on cAMP production in fetal skin fibroblasts is due to indirect modulation of a component of adenylyl cyclase, rather than G-protein-mediated coupling of the receptor with the enzyme. The effect is not mediated by G(s) or G(i), but is probably mediated through the catalytic subunit of adenylyl cyclase. C1 NICHHD, DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT, BLDG 10,ROOM 10N262, BETHESDA, MD 20892 USA. NR 48 TC 14 Z9 14 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1992 VL 131 IS 5 BP 2404 EP 2412 DI 10.1210/en.131.5.2404 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JW338 UT WOS:A1992JW33800057 PM 1330500 ER PT J AU LOHR, M BRENNER, DA ROONEY, JF NELSON, JA AF LOHR, M BRENNER, DA ROONEY, JF NELSON, JA TI APPLICATION OF THE POLYMERASE CHAIN-REACTION IN GASTROENTEROLOGICAL ENDOSCOPY SO ENDOSCOPY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; HERPES-SIMPLEX VIRUS; RAS GENE-MUTATIONS; PEPTIC-ULCER; DNA; AMPLIFICATION; IDENTIFICATION; CARCINOMAS; SEQUENCES; PANCREAS C1 VET ADM MED CTR, DIV GASTROENTEROL, LA JOLLA, CA USA. Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA USA. NIH, BETHESDA, MD 20892 USA. RP LOHR, M (reprint author), UNIV ERLANGEN NURNBERG, DEPT MED 1, DIV GASTROENTEROL & MED RES, KRANKENHAUSSTR 12, W-8520 ERLANGEN, GERMANY. NR 38 TC 4 Z9 4 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD NOV PY 1992 VL 24 IS 9 BP 779 EP 781 DI 10.1055/s-2007-1010582 PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA KE535 UT WOS:A1992KE53500010 PM 1468396 ER PT J AU ANDERSON, MW REYNOLDS, SH YOU, M MARONPOT, RM AF ANDERSON, MW REYNOLDS, SH YOU, M MARONPOT, RM TI ROLE OF PROTOONCOGENE ACTIVATION IN CARCINOGENESIS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID RAS GENE-MUTATIONS; CELL LUNG-CANCER; C-MYC ONCOGENE; HUMAN HEPATOCELLULAR-CARCINOMA; POLYMERASE CHAIN-REACTION; MOUSE SKIN CARCINOGENESIS; BURKITT-LYMPHOMA CELLS; PRIMARY BREAST-CANCER; ANIMAL-MODEL SYSTEMS; EXPOSED BODY SITES AB The accumulation of genetic damage in the forms of activated proto-oncogenes and inactivated tumor-suppressor genes is the driving force in the evolution of a normal cell to a malignant cell. For example, both the activation of ras oncogenes and the inactivation of several suppressor genes. including p53, have been observed in the development of human colon and lung tumors. Point mutations in key codons can activate ras proto-oncogenes and inactivate the p53 suppressor gene. Thus, several critical genes for tumorigenesis are potential targets for carcinogens and radiation that can induce point mutations at low doses. The ras proto-oncogenes are targets for many genotoxic carcinogens. Activation of the ras gene is an early event-probably the ''initiating'' step - in the development of many chemical-induced rodent tumors. ras Oncogenes are observed in more human tumors and at a higher frequency than any other oncogene, and activation of the proto-oncogene may occur at various stages of the carcinogenic process. Numerous proto-oncogenes other than the ras genes have been shown to be activated in human tumors and to a lesser extent in rodent tumors. Mechanisms that induce aberrant expression of proto-oncogenes are gene amplification and chromosomal translocation or gene rearrangement. Amplification of proto-oncogenes and possibly gene overexpression during the absence of gene amplification occur in the development of many human tumors. For a specific tumor type, amplification of any one proto-oncogene may occur at a low frequency, but the frequency of tumors in which at least one proto-oncogene is amplified can be much higher. Proto-oncogene amplification is usually associated with late stages of tumor progression; however, amplified HER2/neu has been observed in early clinical stages of mammary neoplasia. Activation of proto-oncogenes by chromosomal translocation has been detected at a high frequency in several hematopoietic tumors. Non-ras genes have been detected by DNA transfection assays in both human and rodent tumors. For example, ret and trk genes were found to be activated by gene rearrangements in human papillary thyroid carcinomas. Several potentially new types of oncogenes have also been detected by DNA transfection assays. The etiology of the genetic alterations observed in most human tumors is unclear at present. Examples of ras gene activation and those documented for mutations in the p53 gene demonstrate that exogenous conditions can induce oncogenic mutants of normal genes. The genetic alterations observed in most human tumors are probably generated by both spontaneous events and exogenous conditions. RP ANDERSON, MW (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 170 TC 76 Z9 76 U1 0 U2 6 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 NOV PY 1992 VL 98 BP 13 EP 24 DI 10.2307/3431243 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700003 PM 1486840 ER PT J AU DABHOLKAR, M BRADSHAW, L PARKER, RJ GILL, I BOSTICKBRUTON, F MUGGIA, FM REED, E AF DABHOLKAR, M BRADSHAW, L PARKER, RJ GILL, I BOSTICKBRUTON, F MUGGIA, FM REED, E TI CISPLATIN-DNA DAMAGE AND REPAIR IN PERIPHERAL-BLOOD LEUKOCYTES INVIVO AND INVITRO SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID OVARIAN-CANCER PATIENTS; ADDUCT LEVELS; CHEMOTHERAPY; QUANTITATION AB We have extended our studies on the relationship between cisplatin/carboplatin-induced DNA damage in readily accessible tissue(s) and clinical response to therapy. Such an approach may assist in the study of cancer drug resistance and in establishing parameters for assessing human populations for sensitivity to DNA damaging agents in the environment. Platinum-DNA adduct levels were measured by atomic absorbance spectrometry. DNA repair capacity was assessed in human T-lymphocytes by the ability to repair cisplatin lesions in cellular DNA or in transfected plasmid DNA. In a ''blinded'' study of 21 patients receiving combination cisplatin/carboplatin drug therapy, there was a direct relationship between DNA damage in leukocytes and disease response (summary two-sided p = 0.00011). The cohort of patients had 15 different tumor types, suggesting that blood tissue and tumor tissue of an individual may process platinum-DNA damage similarly regardless of the tissue of origin of the tumor. In leukocytes in vivo, persistence and accumulation were prominent features of the cisplatin-DNA adduct profile. Functional DNA repair capacity has been studied in eight human leukocyte cell lines in vitro (three, T-cells; three, B-cells; one, monocytic; one, promyelocytic), using a host cell reactivation assay with cisplatin-damaged pRSVcat. In the three T cell lines studied, host cell reactivation efficiency was directly related to the cells' abilities to repair cisplatin-damaged cellular DNA (correlation coefficient = 0.993). These data suggest that blood tissue and tumor tissue may process platinum-DNA adducts similarly on a molecular level and that human T lymphocytes are a suitable target for a prospective study of the impact of DNA repair on clinical response to platinum compounds. C1 NCI,MED BRANCH,GENITOURINARY CANC SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892. UNIV SO CALIF,NORRIS CANC CTR,LOS ANGELES,CA 90089. NR 21 TC 11 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 NOV PY 1992 VL 98 BP 53 EP 59 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700007 PM 1486863 ER PT J AU WESTON, A CAPORASO, NE PERRIN, LS SUGIMURA, H TAMAI, S KRONTIRIS, TG TRUMP, BF HOOVER, RN HARRIS, CC AF WESTON, A CAPORASO, NE PERRIN, LS SUGIMURA, H TAMAI, S KRONTIRIS, TG TRUMP, BF HOOVER, RN HARRIS, CC TI RELATIONSHIP OF H-RAS-1, L-MYC, AND P53 POLYMORPHISMS WITH LUNG-CANCER RISK AND PROGNOSIS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID FRAGMENT-LENGTH-POLYMORPHISM; GASTRIC-CANCER; BREAST-CANCER; RARE ALLELES; GENE; METASTASIS; SUSCEPTIBILITY; LOCUS; ASSOCIATION; FREQUENCY AB Proto-oncogenes (H-ras-1 and L-myc) and tumor-suppressor gene (p53) loci have been implicated in lung carcinogenesis. DNA restriction fragment length polymorphisms at these gene loci are being evaluated in a case-control study as markers predictive of risk for cancer or of prognosis when cancer is present. The cases and controls had a cigarette-smoking history of 40 or more pack years or other abnormalities in pulmonary function tests, their ages were closely matched (64 years for cases and 61 years for controls) and the ratio of Caucasians to African Americans was close to unity (cases, 0.95:1.00, controls, 1.00:0.88). The H-ras-1 gene contains an insertion deletion polymorphism. Inheritance of rare H-ras-1 alleles, defined by MspI digestion, confers a relative risk for lung cancer of 2.0 (95% confidence interval, 0.5-7.3) for Caucasians and 3.2 (0.9-11.6) for African Americans (74 cases, 67 controls). The L-myc gene sequence has a restriction site (EcoR1) polymorphism between the second and third exons. Inheritance of restriction site-present alleles was reported to confer poor prognosis (presence of lymph node metastases) in Japanese lung cancer patients. This hypothesis was tested in both case-control study subjects (56 cases, 55 controls) and additional surgical cases (40), but no evidence was found to support the hypothesis in the U.S. population. The p53 gene is a tumor-suppressor gene that can encode either a proline or an arginine in the 72nd residue. No associations was found between the minor allele (proline) and diagnosis of lung cancer (76 cases, 68 controls). Importantly, the observed allelic distributions at each of these genetic loci (H-ras-1, L-myc, and p53) were found to be significantly different between African Americans and Caucasians in a U.S. population. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV HAMAMATSU,DEPT PATHOL 1,HAMAMATSU 43131,JAPAN. NATL DEF MED COLL,DEPT LAB MED,TOKOROZAWA,SAITAMA 359,JAPAN. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. TUFTS UNIV,NEW ENGLAND MED CTR HOSP,DEPT HEMATOL ONCOL,BOSTON,MA 02111. RP WESTON, A (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 30 TC 32 Z9 32 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 NOV PY 1992 VL 98 BP 61 EP 67 DI 10.2307/3431248 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700008 PM 1486864 ER PT J AU GONZALEZ, FJ GELBOIN, HV AF GONZALEZ, FJ GELBOIN, HV TI HUMAN CYTOCHROMES-P450 - EVOLUTION AND CDNA-DIRECTED EXPRESSION SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID HUMAN-LIVER; SACCHAROMYCES-CEREVISIAE; METABOLIC-ACTIVATION; CYTOCHROME-P-450; IDENTIFICATION; SEQUENCE; SUBFAMILY; CLONING; AFLATOXIN-B1; POLYMORPHISM AB As the first step in the process of carcinogenesis, most chemical carcinogens require metabolic activation by cytochromes P450 for conversion to highly reactive electrophiles that bind covalently to DNA. Studies in rodents suggest that low or high levels of expression of a single P450 can determine susceptibility or resistance to chemically induced cancer. Although rodent systems have been used to explore the molecular basis of chemical carcinogenesis and to identify chemicals capable of damaging genes and causing cancer, it has been understood that marked species differences exist in the expression, regulation, and catalytic activities of different P450s. Thus, large efforts are underway to study the catalytic activities of human P450s directly by expression of their cDNAs in cultured cells. Two systems are being used: a) transient high-level P450 production in HepG2 cells for analysis of catalytic activities, and b) stable expression in human B-lymphoblastoid cells to study promutagen and procarcinogen activation. These studies define the relative contributions of individual P450 forms to the activation of various chemical carcinogens. The B-lymphoblastoid cDNA expression system can also be used to determine whether a chemical will be hazardous or toxic to humans. The most intriguing aspects of P450s are the occurrence of human genetic polymorphisms in P450 expression, which could be a risk factor for chemical carcinogenesis. The best-studied P450 genetic polymorphism is the debrisoquine/sparteine polymorphism which is due to mutant CYP2D6 alleles. Four mutant alleles have been characterized that account for most of the defective CYP2D6 genes in Caucasians. These can be detected by polymerase chain reaction assays. The expression of other P450s is currently being studied in human tissue specimens to determine whether functional polymorphisms exist with other P450 forms. RP GONZALEZ, FJ (reprint author), NIH,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. NR 38 TC 39 Z9 40 U1 0 U2 2 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 NOV PY 1992 VL 98 BP 81 EP 85 DI 10.2307/3431251 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700011 PM 1486867 ER PT J AU CAPORASO, NE SHIELDS, PG LANDI, MT SHAW, GL TUCKER, MA HOOVER, R SUGIMURA, H WESTON, A HARRIS, CC AF CAPORASO, NE SHIELDS, PG LANDI, MT SHAW, GL TUCKER, MA HOOVER, R SUGIMURA, H WESTON, A HARRIS, CC TI THE DEBRISOQUINE METABOLIC PHENOTYPE AND DNA-BASED ASSAYS - IMPLICATIONS OF MISCLASSIFICATION FOR THE ASSOCIATION OF LUNG-CANCER AND THE DEBRISOQUINE METABOLIC PHENOTYPE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID GENETIC HOST FACTORS; ABO BLOOD-GROUPS; POLYMORPHIC HYDROXYLATION; EXTENSIVE METABOLIZERS; ACETYLATION PHENOTYPE; QUINIDINE TREATMENT; POOR METABOLIZERS; OXIDATION; RISK; DEFICIENT AB Debrisoquine is an antihypertensive drug that is metabolized by cytochrome P450(2D6). Deficient metabolism is inherited as an autosomal recessive condition. We previously reported in a case-control study that extensive metabolizers of debrisoquine were at greater risk of lung cancer compared to poor and intermediate metabolizers. Cloning of the gene that encodes P450(2D6) (CYP2D6) led to the identification of both wild-type and mutant forms of the gene. Subsequently, a DNA-restriction fragment length polymorphism (RFLP) was identified, and a Southern hybridization-based test was developed in an attempt to define the genotype. When the DNA-RFLP test was applied to stored DNA from our study subjects there was neither a significant association with the metabolic phenotype nor an association with lung cancer. Further work has demonstrated that the wild-type gene, which was characterized by a 29-kb allele, can also contain mutations that result in nonfunctional or absent proteins. When these mutations are present, individuals exhibit the poor or intermediate metabolizer phenotype in spite of the presence of the 29-kb putative wild-type allele. Sequence determination of the mutants led to the development of techniques to exploit the polymerase chain reaction, which, together with Southern analysis, have been reported to detect as many as 95% of poor metabolizers. This technique is being used to examine the association of the extensive metabolizer genotype with lung cancer in the subjects from the case-control study. Preliminary results indicate a weak association between the homozygous wild-type genotype and lung cancer; in contrast, the extensive metabolizer phenotype is strongly associated with lung cancer in this subset. Employing this polymerase chain reaction method only, misclassification in the genotype assignment continues to occur, and work is in progress to identify further mutations that may account for subjects who are phenotypically poor metabolizers but possess ''wild-type'' alleles. The phenotyping approach is currently more sensitive, while the genotyping method may be more specific with regard to detection of the deficient metabolizer state in the context of population studies. Increasing use of genotyping is anticipated in future studies. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP CAPORASO, NE (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN439,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Shields, Peter/I-1644-2012; Tucker, Margaret/B-4297-2015 NR 31 TC 23 Z9 23 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 NOV PY 1992 VL 98 BP 101 EP 105 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700014 PM 1362537 ER PT J AU BELL, DA THOMPSON, CL TAYLOR, J MILLER, CR PERERA, F HSIEH, LL LUCIER, GW AF BELL, DA THOMPSON, CL TAYLOR, J MILLER, CR PERERA, F HSIEH, LL LUCIER, GW TI GENETIC MONITORING OF HUMAN POLYMORPHIC CANCER SUSCEPTIBILITY GENES BY POLYMERASE CHAIN-REACTION - APPLICATION TO GLUTATHIONE TRANSFERASE MU SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID TRANS-STILBENE OXIDE; S-TRANSFERASE; DNA; CARCINOGENESIS; EXPRESSION; DELETION; CLONING AB Several genes involved in the metabolism of carcinogens have been found to be polymorphic in human populations and are associated with increased risk of cancer at some sites. This study focuses on the Polymorphic enzyme glutathione transferase mu (GT mu). Smokers with low lymphocyte GT mu activity are at an approximately 2-fold higher risk for lung cancer and an approximately 3-fold higher risk for stomach and colon adenocarcinomas. Recent cloning and sequencing of the GST1 gene has allowed the development of convenient genotyping methods based on restriction fragment length polymorphisms (RFLP) or the polymerase chain reaction (PCR). The GST1 polymorphism has been shown to be a deletion of the gene locus. To detect the presence or absence of the gene we amplified exons 1-5 and/or exons 6-7 of the GST1 gene by PCR. PCR amplification produced bands of 215-bp or 273-bp from individuals with one or two copies of the GST1 allele and no band if the individual was homozygously deleted (0/0). In the exon 6-7 PCR, we co-amplified a 268-bp portion of the beta-globin gene as an internal reference standard for quantitative analysis of product yield. This allowed homozygote individuals (+/+) to be distinguished from heterozygotes (+/0). We have compared the GST1 genotype to lymphocyte GT mu activity measured on trans-stilbene oxide (TSO) in the lymphocytes of 45 individuals. Low GT mu activity (< 67 pmole/min/10(7) cells) was strongly associated (24/24) with the GST1 0/0 genotype. With the exception of one individual, activities greater than 67 pmole/min/10(7) were associated with the presence of the GST1 allele (20/21). Individuals with the highest GT-TSO activity were found to be homozygous for GST1 (+/+), while heterozygotes (+/0) generally had lower activity, suggesting a gene dosage effect in lymphocytes. The allele distribution among four sampled populations varied considerably. In a North Carolina population, 51% (65/127) were GST1 0/0, and this finding is consistent with those of other studies based on phenotypic analysis. In three smaller cohorts, the GST1 0/0 genotype was observed to occur in: 30% (14/47) of Finnish foundry workers, 33% (18/54) of Georgia dye workers, and 62% (74/120) of Taiwanese placental samples. In the future, we shall investigate the mechanistic link between polymorphisms in carcinogen metabolism genes and interindividual variation in measures of DNA damage, such as DNA adducts and hprt mutation frequency. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. COLUMBIA UNIV,SCH PUBL HLTH,NEW YORK,NY 10027. CHANG GUNG MED COLL,DEPT PUBL HLTH,TAIPEI,TAIWAN. RP BELL, DA (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI taylor, jack/0000-0001-5303-6398 FU NIEHS NIH HHS [ES 05294-02] NR 16 TC 92 Z9 97 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 NOV PY 1992 VL 98 BP 113 EP 117 DI 10.2307/3431256 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700016 PM 1486839 ER PT J AU CLARK, G TRITSCHER, A BELL, D LUCIER, G AF CLARK, G TRITSCHER, A BELL, D LUCIER, G TI INTEGRATED APPROACH FOR EVALUATING SPECIES AND INTERINDIVIDUAL DIFFERENCES IN RESPONSIVENESS TO DIOXINS AND STRUCTURAL ANALOGS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID ARYL-HYDROCARBON HYDROXYLASE; O-DEETHYLASE ACTIVITY; AH RECEPTOR; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN TCDD; C57BL/6J MICE; LUNG-CANCER; TOXICITY; INDUCTION; LYMPHOCYTES; DNA AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that is produced inadvertently during the synthesis of some organochlorine compounds, such as the chlorinated phenoxy pesticides. It is biologically and ecologically persistent, with an estimated half-life of 7 years in humans. It possesses high acute toxicity in rodents and is a carcinogen, teratogen, and immunotoxin. In chronic bioassays for carcinogenicity, TCDD at a dose of 10 ng/kg/day increases the incidence of liver tumors in female rats, making it one of the most potent animal carcinogens ever tested. A recent study in humans has shown an increase in the incidence of respiratory tract tumors in workers in chlorinated phenoxy herbicide plants. Considerable controversy and uncertainty remain, however, concerning its carcinogenic potency in humans and the reliability of using animal data to predict human risks. It is generally accepted that most, if not all, of the effects of TCDD require its binding to the Ah receptor. In addition to its toxic effects, TCDD produces a number of biochemical effects, such as induction of CYP1A1, downregulation of binding activity of the estrogen and epidermal growth factor (EGF) receptors, and changes in cytokine pathways. These effects suggest that the Ah receptor plays an important role in regulating the cell cycle. A number of structural analogs of TCDD, such as the polychlorinated dibenzofurans, also interact with the Ah receptor, and they produce the same spectrum of responses as TCDD in animal and cell models. The potency of these compounds is strongly correlated with their binding affinity to the Ah receptor. Perhaps the most sensitive marker of exposure to TCDD in both rodents and humans is induction of a specific isozyme of cytochrome P450 (CYP1A1). Our data suggest that humans are at least as sensitive as rats to CYP1A1 enzyme induction (produced by transcriptional activation of the CYP1A1 gene) and to down-regulation of the EGF receptor. This conclusion is based on data obtained in vivo (accidentally exposed humans and rats subjected to a two-stage model of hepatocarcinogenesis) and in vitro (incubation of human and rodent lymphocytes with TCDD). There is considerable interindividual variation in human responses to TCDD. Our work on ''markers of susceptibility'' suggests that both variation in the amount of Ah receptor and a mutation in the CYP1A1 gene may be responsible for this variation. Since TCDD gives negative results in short-term tests for genotoxicity and does not bind covalently to DNA, it can be considered a prototypical chemical for the study of receptor-mediated carcinogenesis RP CLARK, G (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 49 TC 37 Z9 37 U1 0 U2 3 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 NOV PY 1992 VL 98 BP 125 EP 132 DI 10.2307/3431258 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700018 PM 1336723 ER PT J AU HAYES, RB AF HAYES, RB TI BIOMARKERS IN OCCUPATIONAL-CANCER EPIDEMIOLOGY - CONSIDERATIONS IN STUDY DESIGN SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID BLADDER-CANCER; ACETYLATOR PHENOTYPE; P53 MUTATIONS; CARCINOGENESIS; HUMANS AB Epidemiologic studies of occupational groups have been central to the identification of human carcinogens. The incorporation of a biochemical component into occupational studies of cancer can expand the possibilities for identifying human carcinogens and for understanding the disease process. Two epidemiologic studies of occupation and cancer which include evaluation of biomarkers are described. The association of acetylator phenotype with bladder cancer risk was studied in benzidine-exposed workers. The association of benzene-related leukopenia with leukemia is being studied in benzene-exposed workers. These investigations illustrate issues in the use of biomarkers in epidemiologic studies of cancer risk. Such studies require the identification and characterization of the population at risk. Disease susceptibility factors are amenable for inclusion in these studies and can be statistically modeled as exposure-effect modifiers. Biomarkers of exposure are mainly of importance in short-term longitudinal and cross-sectional studies of exposure and intermediate outcomes and for validation of other data sources. Several sources of error can affect the results of molecular epidemiologic studies. Aside from minimizing laboratory error, consideration must be given in the design and execution of these studies to potential problems in subject selection and field collection of biologic samples and other relevant data. RP HAYES, RB (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20895, USA. NR 34 TC 12 Z9 13 U1 0 U2 1 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 NOV PY 1992 VL 98 BP 149 EP 154 DI 10.2307/3431262 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700022 PM 1486844 ER PT J AU SHIELDS, PG SUGIMURA, H CAPORASO, NE PETRUZZELLI, SF BOWMAN, ED TRUMP, BF WESTON, A HARRIS, CC AF SHIELDS, PG SUGIMURA, H CAPORASO, NE PETRUZZELLI, SF BOWMAN, ED TRUMP, BF WESTON, A HARRIS, CC TI POLYCYCLIC AROMATIC HYDROCARBON DNA ADDUCTS AND THE CYP1A1 RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID LUNG-CANCER; BLOOD-CELLS; LYMPHOCYTES; IDENTIFICATION; CARCINOGEN; BINDING; GENE AB Human cancer risk assessment at a genetic level involves the investigation of carcinogen metabolism and DNA adduct formation. Wide interindividual differences in metabolism result in different DNA adduct levels. For this and other reasons, many laboratories have considered DNA adducts to be a measure of the biologically effective dose of a carcinogen. Techniques for studying DNA adducts using chemically specific assays are becoming available. A modification of the P-32-postlabeling assay for polycyclic aromatic hydrocarbon DNA adducts described here provides potential improvements in quantification. DNA adducts, however, reflect only recent exposure to carcinogens; in contrast, genetic testing for metabolic capacity indicates the extent to which carcinogens can be activated and exert genotoxic effects. Such studies may reflect both separate and integrated risk factors together with DNA adduct levels. A recently described restriction fragment length polymorphism for the CYP1A1, which codes for the cytochrome P450 enzyme primarily responsible for the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons, has been found to be associated with lung cancer risk in a Japanese population. In a subset of individuals enrolled in a U.S. lung cancer case-control study, no association with lung cancer was found. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. RP SHIELDS, PG (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C16,BETHESDA,MD 20892, USA. RI Shields, Peter/I-1644-2012 NR 17 TC 24 Z9 24 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 NOV PY 1992 VL 98 BP 191 EP 194 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700028 PM 1362539 ER PT J AU WATTS, RR LEMIEUX, PM GROTE, RA LOWANS, RW WILLIAMS, RW BROOKS, LR WARREN, SH DEMARINI, DM BELL, DA LEWTAS, J AF WATTS, RR LEMIEUX, PM GROTE, RA LOWANS, RW WILLIAMS, RW BROOKS, LR WARREN, SH DEMARINI, DM BELL, DA LEWTAS, J TI DEVELOPMENT OF SOURCE TESTING, ANALYTICAL, AND MUTAGENICITY BIOASSAY PROCEDURES FOR EVALUATING EMISSIONS FROM MUNICIPAL AND HOSPITAL WASTE COMBUSTORS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID SALMONELLA MUTAGENICITY; COMPLEX-MIXTURES; FLY-ASH; INCINERATORS; CARCINOGENS; EXTRACTS; DIOXINS; ASSAY AB Incineration is currently being used for disposal of about 10% of the solid waste generated in the United States, and this percentage will likely increase as land disposal declines. Siting new incinerators, however, is often controversial because of concerns related to the possibility of adverse health effects and environmental contamination from long-term exposure to stack emissions. Specific concerns relate to the adequacies of a) stack emission testing protocols, b) existing regulations, and c) compliance monitoring and enforcement of regulations. U.S. Environmental Protection Agency laboratories are cooperatively conducting research aimed at developing new testing equipment and procedures that will allow a more comprehensive assessment of the complex mixture of organics that is present in stick emissions. These efforts are directed specifically toward developing source testing equipment and procedures, analytical procedures, and bioassay procedures. The objectives of this study were to field test two types of high-volume source dilution samplers, collect stack samples for use in developing analytical and mutagenicity bioassay procedures, and determine mutagenicity of organics associated with emission particles from two municipal waste combustors and a hospital waste combustor. Data are presented for particle concentrations and emission rates. extractable organic concentrations and emission rates, and Salmonella (Ames) mutagenic potency and emission rates. The mutagenic emission rates and emission factors are compared to other incinerators and combustion sources. C1 US EPA,AIR & ENERGY ENGN RES LAB,RES TRIANGLE PK,NC 27711. NIEHS,RES TRIANGLE PK,NC 27709. ENVIRONM HLTH RES & TESTING INC,RES TRIANGLE PK,NC 27709. RP WATTS, RR (reprint author), US EPA,HLTH EFFECTS RES LAB,MD-68A,RES TRIANGLE PK,NC 27711, USA. NR 26 TC 15 Z9 16 U1 0 U2 5 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 NOV PY 1992 VL 98 BP 227 EP 234 DI 10.2307/3431276 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700036 PM 1486854 ER PT J AU KUROKAWA, Y DAMSTRA, T AF KUROKAWA, Y DAMSTRA, T TI THE 3RD UNITED-STATES JAPAN MEETING ON THE TOXICOLOGICAL CHARACTERIZATION OF ENVIRONMENTAL CHEMICALS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID MOUSE SKIN CARCINOGENESIS; BLADDER-TUMOR PROMOTERS; F344 RATS; TOXICITY CARCINOGENICITY; RENAL TUMORIGENESIS; RODENT CARCINOGENS; POTASSIUM BROMATE; ASCORBIC-ACID; TESTS; URINE AB This report summarizes the discussion of the Third U.S.-Japan Meeting on the Toxicological Characterization of Environmental Chemicals held under the auspices of the U.S.-Japan cooperative in research and development in science and technology. Recent data on the interrelationships between toxicity, cell proliferation, and carcinogenicity are presented. C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. NATL INST HYG SCI,TOKYO,JAPAN. NR 41 TC 1 Z9 1 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 NOV PY 1992 VL 98 BP 281 EP 286 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA KG637 UT WOS:A1992KG63700041 PM 1486859 ER PT J AU THEODORE, WH CARSON, RE ANDREASEN, P ZAMETKIN, A BLASBERG, R LEIDERMAN, DB RICE, K NEWMAN, A CHANNING, M DUNN, B SIMPSON, N HERSCOVITCH, P AF THEODORE, WH CARSON, RE ANDREASEN, P ZAMETKIN, A BLASBERG, R LEIDERMAN, DB RICE, K NEWMAN, A CHANNING, M DUNN, B SIMPSON, N HERSCOVITCH, P TI PET IMAGING OF OPIATE RECEPTOR-BINDING IN HUMAN EPILEPSY USING [F-18] CYCLOFOXY SO EPILEPSY RESEARCH LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; [F-18]CYCLOFOXY; COMPLEX PARTIAL SEIZURE ID POSITRON EMISSION TOMOGRAPHY; REPEATED ELECTROCONVULSIVE SHOCKS; TEMPORAL-LOBE EPILEPSY; RAT-BRAIN; MU-OPIATE; ENKEPHALIN CONTENT; KINETIC-ANALYSIS; MULTIPLE OPIATE; MORPHINE; CYCLOFOXY AB We used [F-18]cyclofoxy (CF), a potent opiate antagonist with affinity for mu and kappa receptors, and the Scanditronix PC1024-7B PET scanner to study 14 patients with complex partial seizures (CPS), and 14 normal controls. Epileptic foci were localized by prolonged EEG-video monitoring. EEG was recorded continuously during each scan. Immediately before CF administration, [O-15]labeled water was used to measure cerebral blood flow, and showed hypoperfusion ipsilateral to the EEG focus. Blood samples (corrected for radiolabeled metabolites) and tissue time-activity data were acquired over 90 min following bolus CF injection. Anatomic regions were outlined directly on the PET images. A kinetic model was used to derive the total volume of distribution (V(t)) in each brain region. Specific binding (V(s)) was determined by subtracting non-specific binding (Vt) measured in a receptor-poor brain region (occipital cortex). Regions with high V(s) included mesial temporal lobes, thalamus, basal ganglia, and frontal cortex. Individual patients appeared to have higher binding in temporal lobe ipsilateral to the EEG focus, but there was no asymmetry for the patients as a group in mean V(t) or V(s) in anterior mesial, posterior mesial, anterior lateral, posterior lateral temporal cortex, thalamus, basal ganglia, or, for V(t), in regions of low specific binding occipital lobe, parietal lobe, cerebellum. C1 NIMH,CTR CLIN,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NIMH,BRAIN IMAGING SECT,BETHESDA,MD 20892. RP THEODORE, WH (reprint author), NINCDS,CLIN EPILEPSY SECT,NIH 10-SN-248,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 39 TC 50 Z9 51 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD NOV PY 1992 VL 13 IS 2 BP 129 EP 139 DI 10.1016/0920-1211(92)90068-5 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA KA586 UT WOS:A1992KA58600005 PM 1334456 ER PT J AU VETTER, R DOSEMECI, M BLAIR, A WACHOLDER, S UNSAL, M ENGIN, K FRAUMENI, JF AF VETTER, R DOSEMECI, M BLAIR, A WACHOLDER, S UNSAL, M ENGIN, K FRAUMENI, JF TI OCCUPATIONAL PHYSICAL-ACTIVITY AND COLON CANCER RISK IN TURKEY SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE COLON CANCER; RISK FACTORS; OCCUPATIONAL ACTIVITY; TURKEY AB A case-control study of 107 colon cancer cases and 486 controls from an oncological clinic in Istanbul was conducted to examine the association between occupational physical activity and colon cancer in Turkey, where incidence of this disease is low. Only two of the four activity measures showed evidence of an increased colon cancer risk for sedentary jobs (time spent sitting OR = 1.5 and occupational energy expenditure OR = 1.6); neither was statistically significant. Subjects below age 55 showed higher risk associated with sedentary jobs than did the older age group, probably due to their adoption of a more western lifestyle, including dietary habits, less activity, and other factors that may interact to increase the risk of colon cancer. C1 SSK OKEMEYDANI HOSP,ONCOL CLIN,ISTANBUL,TURKEY. RP VETTER, R (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 22 Z9 22 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD NOV PY 1992 VL 8 IS 6 BP 845 EP 850 DI 10.1007/BF00145330 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KU826 UT WOS:A1992KU82600014 PM 1294390 ER PT J AU FOMSGAARD, A HIRSCH, VM JOHNSON, PR AF FOMSGAARD, A HIRSCH, VM JOHNSON, PR TI CLONING AND SEQUENCES OF PRIMATE CD4 MOLECULES - DIVERSITY OF THE CELLULAR RECEPTOR FOR SIMIAN IMMUNODEFICIENCY VIRUS HUMAN-IMMUNODEFICIENCY-VIRUS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; ENVELOPE GLYCOPROTEIN; BINDING-SITE; INFECTION; ANTIGEN; DOMAIN; CELLS; RETROVIRUS; PROTEIN; EPITOPE AB To study the interaction between the primate lentiviruses simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) and the CD4 receptor we have cloned and sequenced the CD4 molecule from six non-human primate species: African green monkeys (three subspecies: sabeus, pytherethrus, aethiops), sooty mangabeys, patas monkeys, chimpanzees, rhesus macaques, and pig-tail macaques. Molecular cDNA clones representing CD4 mRNA were generated from total RNA from peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR) amplification including reverse transcriptase in initial reactions followed by two rounds of nested amplifications. Primer sequences were selected from regions conserved among human and rodent CD4 genes. Alignments of deduced amino acid sequences revealed interesting findings. First, all of the primate CD4 molecules were about 90 % identical to the human CD4 sequence except the chimpanzee (98 %). Second, two macaques or two African green monkey subspecies were as distanly related as the human versus chimpanzee sequences. Third, relatedness of CD4 sequences could not be predicted on the basis of geographic origin (Asian vs. African). Finally, upon sequencing several clones from individual monkeys, a low degree of sequence variation (nucleotide substitutions, deletions, and insertions) was found within the same animal, and in case of sooty mangabeys two distict populations of CD4 molecules were present within three of four individuals. The distinguishing features involved eight amino acid changes, including a single lysine deletion relative to a primate consensus sequence in the first complementary-determing region of V1J1. These two CD4 populations were present also at the genomic DNA level and may arrive from the two chromosomal alleles, suggesting the existence of distinct sooty mangabey subspecies. Overall, the V1J1 and to a lesser extent V2J2 were the most variable regions among the sequences examined. By construction and expression in mammalian cell lines of CD4 chimeras in which these regions of the human CD4 were replaced by those of the African green monkey and pig-tail macaques, a higher molecular mass of the CD4 chimeras were obtained in sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggesting that the additional N-linked glycosylation sites present in these monkey CD4 are also used. C1 GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL,WASHINGTON,DC. NIAID,ROCKVILLE,MD. RI Johnson, Philip/A-6892-2009 FU NIAID NIH HHS [N01 AI-72623] NR 35 TC 35 Z9 42 U1 0 U2 2 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 NOV PY 1992 VL 22 IS 11 BP 2973 EP 2981 DI 10.1002/eji.1830221132 PG 9 WC Immunology SC Immunology GA JX918 UT WOS:A1992JX91800031 PM 1425921 ER PT J AU LAZARUS, LH SALVADORI, S GRIECO, P WILSON, WE TOMATIS, R AF LAZARUS, LH SALVADORI, S GRIECO, P WILSON, WE TOMATIS, R TI UNIQUE SEQUENCE IN DELTORPHIN-C CONFERS STRUCTURAL REQUIREMENT FOR DELTA OPIOID RECEPTOR SELECTIVITY SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE DELTORPHIN-C; PEPTIDE SYNTHESIS; OPIOID RECEPTORS ID HIGH-AFFINITY; CONFORMATIONAL PROPERTIES; AMPHIBIAN SKIN; BINDING-SITES; DERMORPHIN; ANALOGS; DERMENKEPHALIN; PEPTIDES; AGONIST; ADDRESS AB A series of deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues were synthesized to assess the consequences of changing anionic and hydrophobic residues on delta receptor selectivity. Analogues with altered C-terminal groups, inverted sequences, or esterified with tert-butyl, benzyl, or ethyl groups revealed that high delta selectivity required an unmodified amino acid sequence. Shifts of Asp and hydrophobic residues decreased delta selectivity due to loss in delta affinity (5- to almost-equal-to 700-fold); mu affinity was unchanged or increased 14-fold. Suppression of charge or deamidation diminished delta selectivity through reduced delta and modified mu affinities. Data provide evidence that a negative charge does not a priori guarantee high selectivity and specific alignment of anionic and hydrophobic residues might facilitate optimum spatial configuration which complements the 8 receptor binding site. C1 UNIV NAPLES,DEPT PHARMACEUT SCI,I-80138 NAPLES,ITALY. UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. RP LAZARUS, LH (reprint author), NATL INST ENVIRONM HLTH SCI,LMIN,POB 12233,MD 1401,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 14 Z9 14 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD NOV PY 1992 VL 27 IS 8 BP 791 EP 797 DI 10.1016/0223-5234(92)90113-F PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KG026 UT WOS:A1992KG02600005 ER PT J AU MIU, P KAROUM, F TOFFANO, G COMMISSIONG, JW AF MIU, P KAROUM, F TOFFANO, G COMMISSIONG, JW TI REGULATORY ASPECTS OF NIGROSTRIATAL DOPAMINERGIC-NEURONS SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE REGULATION; SYNTHESIS; RELEASE; DOPAMINE; RAT ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TRANS-STRIATAL DIALYSIS; ELECTRICAL-STIMULATION; RAT-BRAIN; INTRACEREBRAL DIALYSIS; TYROSINE-HYDROXYLASE; ENDOGENOUS DOPAMINE; INVIVO RELEASE; SPINAL-CORD; METABOLISM AB In the urethane-anesthetized rat, electrical stimulation (10 Hz, 30 s, 250 muA) of the medial forebrain bundle (MFB), at 20-min intervals over an 8-h period, combined with intracerebral microdialysis in the striatum caused: an undiminished increase in the release of dopamine (DA) with each stimulation episode; a decreased efflux of 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA) after the first stimulation only; a delayed increased efflux of DOPAC with no change in HVA; and a poststimulation depression of firing of dopaminergic neurons in the substantia nigra (before, 3.1 +/- 0.7 Hz; after, 1.9 +/- 1.0 Hz; P < 0.05). After the last stimulation episode, the release of DA declined to prestimulation values, while the increased efflux of DOPAC persisted for three more hours. After the infusion of tetrodotoxin (4.0 x 10(-7) M, 1.5 mul, 1.0 mul/min) into the MFB, the basal release of DA was reduced (P < 0.05), while the efflux of DOPAC and HVA was increased (P < 0.05). A model is proposed suggesting that: (1) during increased release of DA in the striatum, the metabolism of DA is decreased; (2) inhibition of nigrostriatal dopaminergic neurons is the usual cause of increased synthesis and metabolism of DA in the striatum; and (3) increased release of DA, and increased synthesis and metabolism of DA in the striatum are not causally linked and are noncoupled processes. C1 NIH,NINDS,LMCN,BLDG 10-5N214,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. MCGILL UNIV,DEPT PHYSIOL,MONTREAL H3G 1Y6,QUEBEC,CANADA. ST ELIZABETH HOSP,CTR NEUROSCI,NEUROPSYCHOPHARMACOL LAB,WASHINGTON,DC 20032. FIDIA RES LABS,I-35031 ABANO TERME,ITALY. NR 46 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD NOV PY 1992 VL 91 IS 3 BP 489 EP 495 PG 7 WC Neurosciences SC Neurosciences & Neurology GA JY907 UT WOS:A1992JY90700012 PM 1483521 ER PT J AU KIM, RY WISTOW, GJ AF KIM, RY WISTOW, GJ TI THE CDNA RPE1 AND MONOCLONAL ANTIBODY-HMB-50 DEFINE GENE-PRODUCTS PREFERENTIALLY EXPRESSED IN RETINAL-PIGMENT EPITHELIUM SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE RETINAL PIGMENT EPITHELIUM; MELANOMA; GENE REGULATION; MOLECULAR CLONING; MONOCLONAL ANTIBODY ID RAT EYE; TRANSTHYRETIN; MELANOCYTES; SEQUENCE; PROTEIN; LOCUS; CELLS; MAPS; DNA RP KIM, RY (reprint author), NEI, MOLEC & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 22 TC 16 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD NOV PY 1992 VL 55 IS 5 BP 657 EP 662 DI 10.1016/0014-4835(92)90170-W PG 6 WC Ophthalmology SC Ophthalmology GA JZ826 UT WOS:A1992JZ82600002 PM 1478275 ER PT J AU MCDONAGH, KT DOVER, GJ DONAHUE, RE NATHAN, DG AGRICOLA, B BYRNE, E NIENHUIS, AW AF MCDONAGH, KT DOVER, GJ DONAHUE, RE NATHAN, DG AGRICOLA, B BYRNE, E NIENHUIS, AW TI HYDROXYUREA-INDUCED HBF PRODUCTION IN ANEMIC PRIMATES - AUGMENTATION BY ERYTHROPOIETIN, HEMATOPOIETIC GROWTH-FACTORS, AND SODIUM-BUTYRATE SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE HBF; ERYTHROPOIETIN; IL-3; GM-CSF; BUTYRATE ID SICKLE-CELL-ANEMIA; FETAL-HEMOGLOBIN PRODUCTION; GAMMA-GLOBIN SYNTHESIS; ADULT ERYTHROID-CELLS; 5-AZACYTIDINE; GENE; STIMULATION; BABOONS; DISEASE; ACTIVATION AB Hydroxyurea, a cell-cycle-specific cytotoxic agent, has been shown to increase fetal hemoglobin (HbF) production. This property makes it an attractive drug for treatment of sickle cell disease and severe beta thalassemia. Its potential efficacy is limited because of a variable and often suboptimal response. Combinations of hydroxyurea and other drugs may induce more clinically significant increases in HbF. We have utilized chronically phlebotomized rhesus monkeys, treated with oral hydroxyurea, to investigate the capacity of several other agents to further augment HbF synthesis. Recombinant human erythropoietin, in super-pharmacologic doses, increased F-reticulocyte production when given on a weekly sequential schedule (3 of 7 days) with hydroxyurea (4 of 7 days), but it was less effective on an alternate day schedule when hydroxyurea was given daily. Neither recombinant human interleukin 3 (IL-3) nor recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), when infused individually, increased F-reticulocytes in animals receiving daily hydroxyurea. Sequential, overlapping infusions of IL-3 and GM-CSF produced a small but statistically significant increase in F-reticulocytes in one of two hydroxy-urea-treated animals. Infusions of sodium butyrate produced a substantial augmentation in F-reticulocyte production in animals chronically treated with hydroxyurea. Thus, our studies have identified several agents that may prove useful in combination with hydroxyurea to achieve clinically beneficial levels of HbF. C1 JOHNS HOPKINS UNIV HOSP,DIV PEDIAT HEMATOL,BALTIMORE,MD 21205. GENET INST CORP,BOSTON,MA. CHILDRENS HOSP MED CTR,DIV PEDIAT,BOSTON,MA 02115. RP MCDONAGH, KT (reprint author), NHLBI,CLIN HEMATOL BRANCH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [R01-HL28028] NR 33 TC 31 Z9 32 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 NOV PY 1992 VL 20 IS 10 BP 1156 EP 1164 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JW994 UT WOS:A1992JW99400003 PM 1385194 ER PT J AU RUHL, S SCHWABE, M PLUZNIK, DH AF RUHL, S SCHWABE, M PLUZNIK, DH TI INTERLEUKIN-1 AUGMENTS THE EXPRESSION OF THE INTERLEUKIN-2 RECEPTOR ALPHA-CHAIN IN INTERLEUKIN-6-STIMULATED MYELOID CELLS BY A TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL MECHANISM SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE INTERLEUKIN-2 RECEPTOR; INTERLEUKIN-6; INTERLEUKIN-1; TRANSCRIPTIONAL; POSTTRANSCRIPTIONAL REGULATION ID PERIPHERAL-BLOOD MONOCYTES; COLONY-STIMULATING FACTOR; GENE-EXPRESSION; IL-2 RECEPTORS; LEUKEMIA CELLS; GROWTH-FACTOR; BETA-CHAIN; GM-CSF; DIFFERENTIATION; SUBUNIT AB We have recently shown that interleukin 6 (IL-6) induces transient expression of the alpha-chain of the interleukin 2 receptor (IL-2Ralpha) in the murine leukemia myeloid M1 cell line. Others have reported that IL-6 and interleukin 1 (IL-1) synergistically enhance the expression of IL-2Ralpha in T cells. Thus, in the present study, we investigated whether IL-1 affects the kinetics of IL-6-induced IL-2Ralpha expression in M1 cells. By cytofluorometry, we find that surface expression of IL-2Ralpha at 24 h after induction by IL-6 is strongly enhanced by IL-1. However, IL-1 does not change the transient kinetics of expression of IL-2Ralpha. Binding data and Scatchard analysis support these results and show an increase from 3100 to 17,620 low-affinity IL-2 binding sites per cell without any change in affinity after induction of M1 cells by the combination of IL-6 and IL-1. By Northern analysis, we find that the increase in IL-2Ralpha surface expression after treatment with IL-6 and IL-1 occurs in parallel with an increase in IL-2Ralpha but not IL-2Rbeta mRNA expression. By nuclear run-on analysis and actinomycin-D chase experiments, we find that the increase in IL-2Ralpha mRNA expression is due to both an increase in IL-2Ralpha gene transcription and to an increase in IL-2Ralpha mRNA stability. These data suggest that the IL-6-induced expression of IL-2Ralpha can be specifically up-regulated by IL-1, however, without affecting the transient nature in expression of IL-2Ralpha. C1 US FDA,CTR BIOL EVALUT & RES,DIV CYTOKINE BIOL,HFB-800,BLDG 29A,ROOM 3B-19,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,FREDERICK CANC RES FACIL,BIOCHEM PHYSIOL LAB,BIOL RESPONSE MODIFIER PROGRAM,FREDERICK,MD 21701. NR 41 TC 4 Z9 4 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 NOV PY 1992 VL 20 IS 10 BP 1208 EP 1215 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JW994 UT WOS:A1992JW99400011 PM 1426100 ER PT J AU MUNGER, BL BENNETT, GJ KAJANDER, KC AF MUNGER, BL BENNETT, GJ KAJANDER, KC TI AN EXPERIMENTAL PAINFUL PERIPHERAL NEUROPATHY DUE TO NERVE CONSTRICTION .1. AXONAL PATHOLOGY IN THE SCIATIC-NERVE SO EXPERIMENTAL NEUROLOGY LA English DT Article ID DEGENERATION; MODEL; DEAFFERENTATION; MONONEUROPATHY; TRANSECTION; ANIMALS; RAT C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT NEUROSCI & ANAT,HERSHEY,PA 17033. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. FU NINDS NIH HHS [NS 19462] NR 33 TC 100 Z9 103 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1992 VL 118 IS 2 BP 204 EP 214 DI 10.1016/0014-4886(92)90037-Q PG 11 WC Neurosciences SC Neurosciences & Neurology GA JY642 UT WOS:A1992JY64200010 PM 1385206 ER PT J AU WARBURG, A TOURAY, M KRETTLI, AU MILLER, LH AF WARBURG, A TOURAY, M KRETTLI, AU MILLER, LH TI PLASMODIUM-GALLINACEUM - ANTIBODIES TO CIRCUMSPOROZOITE PROTEIN PREVENT SPOROZOITES FROM INVADING THE SALIVARY-GLANDS OF AEDES-AEGYPTI SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE PLASMODIUM-GALLINACEUM; MALARIA; SPOROZOITE INFECTIVITY; CIRCUMSPOROZOITE PROTEINS; MONOCLONAL ANTIBODIES TO CIRCUMSPOROZOITE PROTEINS; MOSQUITO SALIVARY GLANDS; AEDES-AEGYPTI ID ANOPHELES-STEPHENSI MOSQUITOS; FALCIPARUM; MALARIA; EXPRESSION; SPOROGONY C1 CTR PESQUISAS RENE RACHOU FIOCRUZ,BR-30190 BELO HORIZON,MG,BRAZIL. RP WARBURG, A (reprint author), NIAID,MALARIA RES LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 18 TC 31 Z9 32 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD NOV PY 1992 VL 75 IS 3 BP 303 EP 307 DI 10.1016/0014-4894(92)90215-V PG 5 WC Parasitology SC Parasitology GA JW787 UT WOS:A1992JW78700005 PM 1426132 ER PT J AU DEGRAFF, WG KRISHNA, MC KAUFMAN, D MITCHELL, JB AF DEGRAFF, WG KRISHNA, MC KAUFMAN, D MITCHELL, JB TI NITROXIDE-MEDIATED PROTECTION AGAINST X-RAY-INDUCED AND NEOCARZINOSTATIN-INDUCED DNA DAMAGE SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE NITROXIDE; RADIATION; NEOCARZINOSTATIN; ANTIMUTAGENICITY; PULSED FIELD GEL ELECTROPHORESIS; ELECTRON SPIN RESONANCE; FREE RADICALS ID DOUBLE-STRAND BREAKS; FIELD GEL-ELECTROPHORESIS; MAMMALIAN-CELLS; INDUCED MUTATION; CYTO-TOXICITY; CHO CELLS; RADIATION; CALIBRATION; LOCUS AB The stable free radical Tempol (4-hydroxy-2,2.6,6-tetramethyl-piperidinyloxy) has been shown to protect against X-ray-induced cytotoxicity and hydrogen peroxide- or xanthine oxidase-induced cytotoxicity and mutagenicity. The ability of Tempol to protect against X-ray- or neocarzinostatin (NCS)-induced mutagenicity or DNA double-strand breaks (dsb) was studied in Chinese hamster cells. Tempol (50 mM) provided a protection factor of 2.7 against X-ray-induced mutagenicity in Chinese hamster ovary (CHO) AS52 cells, with a protection factor against cytotoxicity of 3.5. Using the field inversion gel electrophoresis technique of measuring DNA dsb, 50 mM Tempol provides a threefold reduction in DNA damage at an X-ray dose of 40 Gy. For NCS-induced damage, Tempol increased survival from 9% to 80% at 60 ng/mL NCS and reduced mutation induction by a factor of approximately 3. DNA dsb were reduced by a factor of approximately 7 at 500 ng/mL NCS. Tempol is representative of a class of stable nitroxide free radical compounds that have superoxide dismutase-mimetic activity, can oxidize metal ions such as ferrous iron that are complexed to DNA, and may also detoxify radiation-induced organoperoxide radicals by competitive scavenging. The NCS chromophore is reduced by sulfhydryls to an active form. Electron spin resonance (ESR) spectroscopy shows that 2-mercaptoethanol-activated NCS reacts with Tempol 3.5 times faster than does unactivated NCS. Thus, Tempol appears to inactivate the NCS chromophore before a substantial amount of DNA damage occurs. RP DEGRAFF, WG (reprint author), NCI,RADIAT ONCOL BRANCH,RADIOBIOL SECT,BLDG 10,RM B3B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 33 Z9 35 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 NOV PY 1992 VL 13 IS 5 BP 479 EP 487 DI 10.1016/0891-5849(92)90142-4 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA JU876 UT WOS:A1992JU87600002 PM 1459474 ER PT J AU CHIUEH, CC KRISHNA, G TULSI, P OBATA, T LANG, K HUANG, SJ MURPHY, DL AF CHIUEH, CC KRISHNA, G TULSI, P OBATA, T LANG, K HUANG, SJ MURPHY, DL TI INTRACRANIAL MICRODIALYSIS OF SALICYLIC-ACID TO DETECT HYDROXYL RADICAL GENERATION THROUGH DOPAMINE AUTOOXIDATION IN THE CAUDATE-NUCLEUS - EFFECTS OF MPP SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Note DE HYDROXYL RADICAL; MPTP, MPP+; SALICYLIC ACID; DOPAMINE; PARKINSONS DISEASE; FREE RADICALS ID RAT STRIATUM; LIQUID-CHROMATOGRAPHY; PARKINSONS-DISEASE; INVIVO; AUTOXIDATION; SEROTONIN; INCREASES; DIALYSIS; TOXICITY; ASSAY AB Ringer's solution containing salicylic acid (5 nmol/mul/min) was infused directly through an intracranial microdialysis probe to detect the generation of hydroxyl radicals (.OH) reflected by the formation of dihydroxybenzoic acids (DHBA) in the caudate nucleus of anesthetized rats. Brain dialysate was assayed for dopamine, 2,3-, and 2.5-DHBA by a high-pressure liquid chromatography-electrochemical (HPLC-EC) procedure. 1-Methyl-4-phenylpyridinium ions (MPP+, 0 to 150 nmol) increased dose-dependently the release of dopamine and the formation of DHBA. A positive linear correlation between the release of dopamine and the formation of approximately 1.3- or 2.5-DHBA was observed (R2 = .98). The present results demonstrate the validity of the use of not only 2,3-DHBA but also 2,5-DHBA as an in vivo index of oxidative damage generated by, reactive .OH radicals. In conclusion, the present study demonstrates a novel use of intracranial microdialysis of salicylic acid to assess the oxidative damage elicited by .OH in living brain. C1 NHLBI,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. RP CHIUEH, CC (reprint author), NIMH,NIH BLDG 10,RM 30 41,BETHESDA,MD 20892, USA. NR 21 TC 231 Z9 234 U1 1 U2 5 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 NOV PY 1992 VL 13 IS 5 BP 581 EP 583 DI 10.1016/0891-5849(92)90151-6 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA JU876 UT WOS:A1992JU87600011 PM 1334031 ER PT J AU WAALKES, MP REHM, S AF WAALKES, MP REHM, S TI CARCINOGENICITY OF ORAL CADMIUM IN THE MALE WISTAR (WF/NCR) RAT - EFFECT OF CHRONIC DIETARY ZINC-DEFICIENCY SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID DOSE-RESPONSE ANALYSIS; PROSTATE-CANCER; CRL-(WI)BR RATS; TUMOR-INDUCTION; INJECTION SITE; TESTES; CHLORIDE; TOXICITY; SINGLE; MICE C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,PATHOGENESIS SECT,FREDERICK,MD 21702. RP WAALKES, MP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 44 TC 70 Z9 71 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1992 VL 19 IS 4 BP 512 EP 520 DI 10.1016/0272-0590(92)90089-Z PG 9 WC Toxicology SC Toxicology GA JY649 UT WOS:A1992JY64900006 PM 1426709 ER PT J AU DIETZ, DD ELWELL, MR DAVIS, WE MEIRHENRY, EF AF DIETZ, DD ELWELL, MR DAVIS, WE MEIRHENRY, EF TI SUBCHRONIC TOXICITY OF BARIUM-CHLORIDE DIHYDRATE ADMINISTERED TO RATS AND MICE IN THE DRINKING-WATER SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID LIFE-TERM; SULFATE; TESTS C1 SRI INT,TOXICOL LAB,MENLO PK,CA 94025. RP DIETZ, DD (reprint author), NIEHS,NATL TOXICOL PROGRAM,DIV TOXICOL RES & TESTING,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-28015-01] NR 54 TC 16 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1992 VL 19 IS 4 BP 527 EP 537 DI 10.1016/0272-0590(92)90091-U PG 11 WC Toxicology SC Toxicology GA JY649 UT WOS:A1992JY64900008 PM 1426711 ER PT J AU METZ, DC PISEGNA, JR FISHBEYN, VA BENYA, RV FEIGENBAUM, KM KOVIACK, PD JENSEN, RT AF METZ, DC PISEGNA, JR FISHBEYN, VA BENYA, RV FEIGENBAUM, KM KOVIACK, PD JENSEN, RT TI CURRENTLY USED DOSES OF OMEPRAZOLE IN ZOLLINGER-ELLISON SYNDROME ARE TOO HIGH SO GASTROENTEROLOGY LA English DT Article ID GASTRIC-ACID SECRETION; INTRAGASTRIC ACIDITY; PLASMA GASTRIN; DUODENAL-ULCER; LOCALIZATION; MANAGEMENT; RANITIDINE; SYMPTOMS; POTENT C1 NIDDKD,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892. NR 42 TC 67 Z9 67 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1992 VL 103 IS 5 BP 1498 EP 1508 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JV478 UT WOS:A1992JV47800010 PM 1426868 ER PT J AU EVERHART, JE HOOFNAGLE, JH AF EVERHART, JE HOOFNAGLE, JH TI HEPATITIS-B-RELATED END-STAGE LIVER-DISEASE SO GASTROENTEROLOGY LA English DT Editorial Material ID PROGNOSTIC FACTORS; NATURAL COURSE; CIRRHOSIS; SURVIVAL; ANTIGEN C1 NIDDKD,DIV DIGEST DIS & NUTR,BETHESDA,MD. NR 23 TC 8 Z9 11 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 NOV PY 1992 VL 103 IS 5 BP 1692 EP 1694 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JV478 UT WOS:A1992JV47800038 PM 1426889 ER PT J AU GAHL, WA GOODMAN, Z OLSON, J AF GAHL, WA GOODMAN, Z OLSON, J TI INDIAN CHILDHOOD CIRRHOSIS - NEED FOR UNIFORM CRITERIA - REPLY SO GASTROENTEROLOGY LA English DT Letter C1 ARMED FORCES INST PATHOL,DEPT HEPAT PATHOL,WASHINGTON,DC 20306. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. RP GAHL, WA (reprint author), NICHHD,HUMAN GENET BRANCH,ROOM 9S242,BLDG 10,BETHESDA,MD 20892, USA. NR 1 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1992 VL 103 IS 5 BP 1709 EP 1709 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JV478 UT WOS:A1992JV47800045 ER PT J AU STRAUS, E RAUFMAN, JP SAMUEL, S WAYE, JD METZ, DC PISEGNA, JR JENSEN, RT AF STRAUS, E RAUFMAN, JP SAMUEL, S WAYE, JD METZ, DC PISEGNA, JR JENSEN, RT TI ENDOSCOPIC CURE OF THE ZOLLINGER-ELLISON SYNDROME SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTRINOMAS C1 CUNY MT SINAI SCH MED,DIV GASTROENTEROL,NEW YORK,NY 10029. NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. RP STRAUS, E (reprint author), SUNY HLTH SCI CTR,DIV DIGEST DIS,BOX 1196,450 CLARKSON AVE,BROOKLYN,NY 11203, USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV-DEC PY 1992 VL 38 IS 6 BP 709 EP 711 DI 10.1016/S0016-5107(92)70572-0 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KE058 UT WOS:A1992KE05800015 PM 1473676 ER PT J AU HILL, DR KELLEHER, K SHUMAKER, SA AF HILL, DR KELLEHER, K SHUMAKER, SA TI PSYCHOSOCIAL INTERVENTIONS IN ADULT PATIENTS WITH CORONARY HEART-DISEASE AND CANCER - A LITERATURE-REVIEW SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; STRESS-MONITORING-PROGRAM; BYPASS GRAFT-SURGERY; PSYCHOLOGICAL INTERVENTION; PSYCHIATRIC INTERVENTION; RECOVERY; SUPPORT; THERAPY; TRIAL; PSYCHOTHERAPY AB A growing body of evidence suggests that chronic medical illness is associated with an increased prevalence and incidence of psychiatric and psychological disturbances. The present literature review is based on two theses: first, that chronic illness is viewed as a stressor and is associated with increased psychological distress, and secondly, that interventions can minimize the distress. A review of the studies conducted with adult patients diagnosed either with coronary heart disease or cancer suggests that psychosocial interventions are, in general, efficacious in relieving self-reported psychological distress. The review also recommends psychosocial interventions for high-risk patients rather than all patients, and that researchers need to identify other outcomes such as health care costs, disability, days in hospital, morbidity, and mortality in order to convince policy makers that these interventions are worthwhile. Recommendations for future research are also discussed. C1 ARKANSAS CHILDRENS HOSP,LITTLE ROCK,AR 72202. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. RP HILL, DR (reprint author), NHLBI,BEHAV MED BRANCH,FED BLDG,ROOM 216,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 55 TC 24 Z9 24 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV PY 1992 VL 14 IS 6 SU S BP S28 EP S42 PG 15 WC Psychiatry SC Psychiatry GA KE287 UT WOS:A1992KE28700004 PM 1340846 ER PT J AU WHANGPENG, J KNUTSEN, T THEIL, K HOROWITZ, ME TRICHE, T AF WHANGPENG, J KNUTSEN, T THEIL, K HOROWITZ, ME TRICHE, T TI CYTOGENETIC STUDIES IN SUBGROUPS OF RHABDOMYOSARCOMA SO GENES CHROMOSOMES & CANCER LA English DT Article ID ROUND CELL TUMORS; ALVEOLAR RHABDOMYOSARCOMA; CHROMOSOMAL TRANSLOCATION; CHILDHOOD RHABDOMYOSARCOMA; SOLID TUMORS; RETINOBLASTOMAS; (2-13)(Q37-Q14); BREAKPOINT; SARCOMAS; LINE AB Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and accounts for 10% of all solid tumors in children. There are three different histologic forms of this tumor: embryonal (RMS-E), alveolar (RMS-A), and primitive (RMS-P). Among these, the embryonal form has responded well to chemotherapy. Identification of the correct subtype is important for both the management and treatment of this malignancy. However, the histopathologic classification of RMS is sometimes difficult and distinguishing between the embryonic and primitive forms can present a diagnostic dilemma. Chromosomal abnormalities have been observed in all subtypes. We present the cytogenetic findings in six cases of RMS or related sarcoma. All four cases with RMS-A had both numerical and structural abnormalities in the tumor and involved bone marrow specimens. Three patients had a common marker, t(2;13)(q37;q14), and one patient had a variant marker involving 13q14, t(1;13) (p36;q14), and double minutes (dmin). The single embryonal RMS patient had modal chromosome numbers in the hypertriploid range and extensive structural abnormalities; the t(2;13) was not present, but translocation of 13q to both 1q and 2p was observed, der(1)t(1;13)(q21;q14) and der(2)t(2;13)(p25;q14). The patient with primitive type RMS had a hypodiploid line with several markers, including a complex translocation involving chromosomes 5 and 13 with a breakpoint at 13q14, and t(11;22)(q24;q12), a chromosome marker heretofore found only in Ewing's sarcoma and related tumors. This patient had atypical RMS with mixed neural and myogenic elements. The significance of these chromosomal markers and their importance in the characterization of childhood tumors are discussed, along with a review of the literature. C1 NIH,PEDIAT BRANCH,BETHESDA,MD 20892. OHIO STATE UNIV HOSP,DIV CYTOGENET,COLUMBUS,OH 43210. CHILDRENS HOSP LOS ANGELES,DEPT PATHOL & LAB MED,LOS ANGELES,CA. RP WHANGPENG, J (reprint author), NIH,DEPT MED,MED BRANCH,BETHESDA,MD 20892, USA. NR 50 TC 85 Z9 86 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD NOV PY 1992 VL 5 IS 4 BP 299 EP 310 DI 10.1002/gcc.2870050405 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA KA016 UT WOS:A1992KA01600004 PM 1283318 ER PT J AU NAJFELD, V MENNINGER, J BALLARD, SG DEGUCHI, Y WARD, DC KEHRL, JH AF NAJFELD, V MENNINGER, J BALLARD, SG DEGUCHI, Y WARD, DC KEHRL, JH TI 2 DIVERGED HUMAN HOMEOBOX GENES INVOLVED IN THE DIFFERENTIATION OF HUMAN HEMATOPOIETIC PROGENITORS MAP TO CHROMOSOME-1, BANDS-Q41-42.1 SO GENES CHROMOSOMES & CANCER LA English DT Article ID DNA-BINDING DOMAIN; TRANSCRIPTION FACTOR; INSITU HYBRIDIZATION; CELLS; DROSOPHILA; PROTEIN; ORGANIZATION; EXPRESSION; INTERPHASE; RESOLUTION AB Proteins encoded by homeobox containing genes are sequence-specific DNA binding proteins implicated in the control of gene expression in both developing and adult tissues. Two recently characterized human homeobox genes, HB9 and HB24, are highly expressed in CD34-positive marrow cells but not in CD34-depleted marrow cells, Their expression is readily down-regulated during the differentiation of hematopoietic progenitors to specific cell lineages. In this study, genomic DNA fragments isolated with HB9 (3 kb) and HB24 (6 kb) cDNAs were used to map their chromosomal location by fluorescence in situ hybridization. Both HB9 and HB24 DNA probes gave specific hybridization signals on chromosome 1. The hybridization loci were identified by combining fluorescence images of the probe signals with fluorescence banding patterns generated by cohybridization in situ with an Alu probe (R-like banding) and by DAPI staining (G-like). The results demonstrate that the loci of the HB24 and HB9 genes are within bands 1q41-q42. 1. A cohybridization experiment utilizing both probes with two-color fluorescence imaging could not resolve separate loci for the two genes. C1 YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP NAJFELD, V (reprint author), CUNY MT SINAI SCH MED,POLLY ANNENBERG LEVEE HEMATOL CTR,TUMOR CYTOGENET LAB,BOX 1079,NEW YORK,NY 10029, USA. FU NHGRI NIH HHS [HG-07272] NR 27 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD NOV PY 1992 VL 5 IS 4 BP 343 EP 347 DI 10.1002/gcc.2870050410 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA KA016 UT WOS:A1992KA01600009 PM 1283323 ER PT J AU BAKER, TA MIZUUCHI, K AF BAKER, TA MIZUUCHI, K TI DNA-PROMOTED ASSEMBLY OF THE ACTIVE TETRAMER OF THE MU-TRANSPOSASE SO GENES & DEVELOPMENT LA English DT Article DE PHAGE-MU; DNA TRANSPOSITION; HU; MUA TETRAMER; ENHANCER ID SITE-SPECIFIC RECOMBINATION; STRAND-TRANSFER-REACTION; INTEGRATION HOST FACTOR; BACTERIOPHAGE-MU; FLP RECOMBINASE; PHAGE-MU; PROTEIN; ENDS; MECHANISM; COMPLEXES AB A stable tetramer of the Mu transposase (MuA) bound to the ends of the Mu DNA promotes recombination. Assembly of this active protein-DNA complex from monomers of MuA requires an intricate array of MuA protein-binding sites on supercoiled DNA, divalent metal ions, and the Escherichia coli HU protein. Under altered reaction conditions, many of these factors stimulate assembly of the MuA tetramer but are not essential, allowing their role in formation of the complex to be analyzed. End-type MuA-binding sites and divalent metal ions are most critical and probably promote a conformational change in MuA that is necessary for multimerization. Multiple MuA-binding sites on the DNA contribute synergistically to tetramer formation. DNA superhelicity assists cooperativity between the sites on the two Mu DNA ends if they are properly oriented. HU specifically promotes assembly involving the left end of the Mu DNA. In addition to dissecting the assembly pathway, these data demonstrate that the tetrameric conformation is intrinsic to MuA and constitutes the form of the protein active in catalysis. RP BAKER, TA (reprint author), NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 31 TC 101 Z9 102 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV PY 1992 VL 6 IS 11 BP 2221 EP 2232 DI 10.1101/gad.6.11.2221 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA JX846 UT WOS:A1992JX84600018 PM 1330829 ER PT J AU HOOPES, CW TAKETO, M OZATO, K LIU, Q HOWARD, TA LINNEY, E SELDIN, MF AF HOOPES, CW TAKETO, M OZATO, K LIU, Q HOWARD, TA LINNEY, E SELDIN, MF TI MAPPING OF THE MOUSE RXR LOCI ENCODING NUCLEAR-RETINOID-X RECEPTORS RXR-ALPHA, RXR-BETA, AND RXR-GAMMA SO GENOMICS LA English DT Article ID ACID RECEPTOR; HEPATOCELLULAR-CARCINOMA; MESSENGER-RNA; TRANSCRIPTION FACTOR; GENE; IDENTIFICATION; PROTEIN; CELLS; INDUCTION; SEQUENCE C1 DUKE UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA39064]; NHGRI NIH HHS [HG00101]; NICHD NIH HHS [HD21430] NR 66 TC 34 Z9 34 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1992 VL 14 IS 3 BP 611 EP 617 DI 10.1016/S0888-7543(05)80159-4 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JW352 UT WOS:A1992JW35200009 PM 1358808 ER PT J AU REMMERS, EF GOLDMUNTZ, EA CASH, JM CROFFORD, LJ MISIEWICZPOLTORAK, B ZHA, HB WILDER, RL AF REMMERS, EF GOLDMUNTZ, EA CASH, JM CROFFORD, LJ MISIEWICZPOLTORAK, B ZHA, HB WILDER, RL TI GENETIC-MAP OF 9 POLYMORPHIC LOCI COMPRISING A SINGLE LINKAGE GROUP ON RAT CHROMOSOME-10 - EVIDENCE FOR LINKAGE CONSERVATION WITH HUMAN CHROMOSOME-17 AND MOUSE CHROMOSOME-11 SO GENOMICS LA English DT Article ID PROTEIN; IDENTIFICATION; HORMONE; PRIMERS; STRAINS; LINES; LEWIS RP REMMERS, EF (reprint author), NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892, USA. RI Crofford, Leslie/J-8010-2013 NR 24 TC 50 Z9 51 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1992 VL 14 IS 3 BP 618 EP 623 DI 10.1016/S0888-7543(05)80160-0 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JW352 UT WOS:A1992JW35200010 PM 1358809 ER PT J AU KEATS, BJB TODOROV, AA ATWOOD, LD PELIAS, MZ HEJTMANCIK, JF KIMBERLING, WJ LEPPERT, M LEWIS, RA SMITH, RJH AF KEATS, BJB TODOROV, AA ATWOOD, LD PELIAS, MZ HEJTMANCIK, JF KIMBERLING, WJ LEPPERT, M LEWIS, RA SMITH, RJH TI LINKAGE STUDIES OF USHER SYNDROME TYPE-1 - EXCLUSION RESULTS FROM THE USHER SYNDROME CONSORTIUM SO GENOMICS LA English DT Article ID SYNDROME TYPE-II; MAPPED GENES; COMMITTEE; CHROMOSOME-1Q; LOCALIZATION; ORDER C1 BOYS TOWN NATL RES HOSP,CTR HEREDITARY COMMUN DISORDERS,OMAHA,NE 68131. NEI,BETHESDA,MD 20892. UNIV UTAH,HLTH SCI CTR,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84132. UNIV UTAH,HLTH SCI CTR,DEPT HUMAN GENET,SALT LAKE CITY,UT 84132. BAYLOR COLL MED,CULLEN EYE INST,HOUSTON,TX 77030. UNIV IOWA HOSP & CLIN,DEPT OTOLARYNGOL,IOWA CITY,IA 52242. RP KEATS, BJB (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT BIOMETRY & GENET,NEW ORLEANS,LA 70112, USA. FU NCRR NIH HHS [1 P41 RR03655]; NHGRI NIH HHS [HG00343]; NIDCD NIH HHS [DC00677] NR 26 TC 3 Z9 3 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 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1992 VL 14 IS 3 BP 707 EP 714 DI 10.1016/S0888-7543(05)80172-7 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JW352 UT WOS:A1992JW35200022 PM 1427898 ER PT J AU YI, TL GILBERT, DJ JENKINS, NA COPELAND, NG IHLE, JN AF YI, TL GILBERT, DJ JENKINS, NA COPELAND, NG IHLE, JN TI ASSIGNMENT OF A NOVEL PROTEIN TYROSINE PHOSPHATASE GENE (HCPH) TO MOUSE CHROMOSOME-6 SO GENOMICS LA English DT Note ID EXPRESSION; LEUKEMIA C1 ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, 332 N LAUDERDALE, MEMPHIS, TN 38105 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NCI NIH HHS [P30 CA21765, N01-CO-74101]; NIDDK NIH HHS [R01 DK42932] NR 11 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1992 VL 14 IS 3 BP 793 EP 795 DI 10.1016/S0888-7543(05)80189-2 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JW352 UT WOS:A1992JW35200039 PM 1427910 ER PT J AU MOCK, BA CONTENTE, S KENYON, K FRIEDMAN, RM KOZAK, CA AF MOCK, BA CONTENTE, S KENYON, K FRIEDMAN, RM KOZAK, CA TI THE GENE FOR LYSYL OXIDASE MAPS TO MOUSE CHROMOSOME-18 SO GENOMICS LA English DT Note ID EXPERIMENTAL HEPATIC-FIBROSIS; MENKES SYNDROME; ASSIGNMENT; RRG C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. RP MOCK, BA (reprint author), NCI,GENET LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CB2-5584, R01 CA37351] NR 17 TC 16 Z9 17 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 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1992 VL 14 IS 3 BP 822 EP 823 DI 10.1016/S0888-7543(05)80201-0 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JW352 UT WOS:A1992JW35200051 PM 1358813 ER PT J AU STETLERSTEVENSON, WG LIOTTA, LA SELDIN, MF AF STETLERSTEVENSON, WG LIOTTA, LA SELDIN, MF TI LINKAGE ANALYSIS DEMONSTRATES THAT THE TIMP-2 LOCUS IS ON MOUSE CHROMOSOME-11 SO GENOMICS LA English DT Note ID TISSUE INHIBITOR; RECEPTOR C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MICROBIOL,DURHAM,NC 27710. RP STETLERSTEVENSON, WG (reprint author), NCI,DCBDC,PATHOL LAB,TUMOR INVAS & METASTASIS SECT,FREDERICK,MD 21701, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NHGRI NIH HHS [HG-00101] NR 17 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1992 VL 14 IS 3 BP 828 EP 829 DI 10.1016/S0888-7543(05)80205-8 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JW352 UT WOS:A1992JW35200055 PM 1427919 ER PT J AU CORPAS, E HARMAN, SM BLACKMAN, MR AF CORPAS, E HARMAN, SM BLACKMAN, MR TI SERUM IGF-BINDING PROTEIN-3 IS RELATED TO IGF-I, BUT NOT TO SPONTANEOUS GH RELEASE, IN HEALTHY OLD MEN SO HORMONE AND METABOLIC RESEARCH LA English DT Note ID GROWTH-HORMONE; AGE C1 FRANCIS SCOTT KEY MED CTR,DEPT MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. RP CORPAS, E (reprint author), NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,ENDOCRINOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NCRR NIH HHS [M01-RR02719] NR 10 TC 23 Z9 23 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV PY 1992 VL 24 IS 11 BP 543 EP 545 DI 10.1055/s-2007-1003385 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JX934 UT WOS:A1992JX93400012 PM 1280614 ER PT J AU XIAO, H MERRIL, CR POLYMEROPOULOS, MH AF XIAO, H MERRIL, CR POLYMEROPOULOS, MH TI DINUCLEOTIDE REPEAT POLYMORPHISMS AT THE D3S1246 AND D3S1247 LOCI SO HUMAN MOLECULAR GENETICS LA English DT Note C1 ST ELIZABETH HOSP, NATL INST MENTAL HLTH, CTR NEUROSCI, WASHINGTON, DC 20032 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1992 VL 1 IS 8 BP 652 EP 652 DI 10.1093/hmg/1.8.652 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JY377 UT WOS:A1992JY37700019 PM 1301177 ER PT J AU RISINGER, JI BOYD, J AF RISINGER, JI BOYD, J TI DINUCLEOTIDE REPEAT POLYMORPHISM IN THE HUMAN DCC GENE AT CHROMOSOME 18Q21 SO HUMAN MOLECULAR GENETICS LA English DT Note C1 NIEHS, MOLEC CARCINOGENESIS LAB, GENE EXPRESS SECT, RES TRIANGLE PK, NC 27709 USA. NR 1 TC 36 Z9 37 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1992 VL 1 IS 8 BP 657 EP 657 DI 10.1093/hmg/1.8.657-a PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JY377 UT WOS:A1992JY37700027 PM 1301182 ER PT J AU POLYMEROPOULOS, MH XIAO, H MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H MERRIL, CR TI TETRANUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN MYELIN BASIC-PROTEIN GENE (MBP) SO HUMAN MOLECULAR GENETICS LA English DT Note ID SEQUENCE C1 ST ELIZABETH HOSP, NATL INST MENTAL HLTH, CTR NEUROSCI, WASHINGTON, DC 20032 USA. NR 3 TC 49 Z9 50 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1992 VL 1 IS 8 BP 658 EP 658 DI 10.1093/hmg/1.8.658 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JY377 UT WOS:A1992JY37700028 PM 1284472 ER PT J AU BASSER, PJ WIJESINGHE, RS ROTH, BJ AF BASSER, PJ WIJESINGHE, RS ROTH, BJ TI THE ACTIVATING FUNCTION FOR MAGNETIC STIMULATION DERIVED FROM A 3-DIMENSIONAL VOLUME CONDUCTOR MODEL SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Note ID ELECTROMAGNETIC INDUCTION; NERVE-STIMULATION AB A three-dimensional volume conductor model of magnetic stimulation is proposed that relates transmembrane potential of an axon to the induced electric field in a uniform volume conductor. This model validates assumptions used to derive a one-dimensional cable model of magnetic stimulation (Roth & Basser, IEEE Trans. Biomed. Eng., vol. 37, pp. 588-597, 1990) of unmyelinated axons. The three-dimensional volume conductor model reduces to this one-dimensional cable equation forced by the activating function, -partial derivative (A)z/partial derivative z. C1 TULANE UNIV,DEPT BIOMED ENGN,NEW ORLEANS,LA 70118. RP BASSER, PJ (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Roth, Bradley/A-4920-2008; Basser, Peter/H-5477-2011 NR 19 TC 29 Z9 34 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD NOV PY 1992 VL 39 IS 11 BP 1207 EP 1210 DI 10.1109/10.168686 PG 4 WC Engineering, Biomedical SC Engineering GA JY684 UT WOS:A1992JY68400011 PM 1487283 ER PT J AU CHOPRA, RK CARROLL, MP MAY, WS BHATIA, SK MARGOLICK, JB NAGEL, JE ADLER, WH AF CHOPRA, RK CARROLL, MP MAY, WS BHATIA, SK MARGOLICK, JB NAGEL, JE ADLER, WH TI 4 INTERLEUKIN-2 SURFACE BINDING-PROTEINS DETECTED IN RAT SPLEEN-CELLS SO IMMUNOLOGY LA English DT Article ID BETA-CHAIN; MOLECULAR-CLONING; RECEPTOR COMPLEX; CROSS-LINKING; IL-2 RECEPTOR; ALPHA-CHAIN; EXPRESSION; SUBUNIT; LYMPHOCYTES; ACTIVATION AB Four specific interleukin-2 (IL-2) surface binding proteins can be detected by covalent cross-linking of[I-125]IL-2 to rat spleen cells that have been activated with various stimuli including concanavalin A (Con A), phytohaemagglutinin (PHA), calcium ionophore, and phorbol dibutyrate (PDB) with or without calcium ionophore. These four cross-linked proteins could not be demonstrated in either unstimulated T cells or in activated T cells when binding was performed in the presence of a 20-100-fold excess of unlabelled IL-2. The molecular weights of the four cross-linked proteins, after subtraction of the molecular weight contribution of IL-2 are: 53,000, 70,000, 90,000 and 118,000. The 53,000 MW protein was identified as the rat IL-2 receptor (IL-2R) alpha-chain by immune precipitation. Additionally, results suggest that the rat IL-2R alpha-chain is tightly complexed to both the 118,000 and 90,000 MW IL-2 binding proteins. Purification of surface labelled proteins from activated cells using IL-2 affinity chromatography yields four proteins with similar molecular weight to those identified by cross-linking plus an additional non-ligand cross-linked protein of 46,000 MW. The 46,000 MW band may be a non-binding associated protein since it was not seen following [I-125]IL-2 binding cross-linking. Tryptic digests and two-dimensional separation of the affinity-isolated proteins indicate that unique peptide maps are generated for the 46,000, 53,000 and 70,000 MW proteins and excludes the possibility that the bands identified by cross-linking represents cross-linking of multiple ligands to the 53,000 MW subunit. However, the 90,000 and 118,000 MW bands yield peptide maps that closely resemble each other suggesting that these binding proteins may be related. These results suggest that at least four IL-2 surface binding proteins may constitute the rat IL-2R system. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,CTR ONCOL,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,BALTIMORE,MD 21224. RP CHOPRA, RK (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [CA47993, CA44649] NR 24 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1992 VL 77 IS 3 BP 338 EP 344 PG 7 WC Immunology SC Immunology GA JW035 UT WOS:A1992JW03500004 PM 1478680 ER PT J AU WINKELSTEIN, A HESS, RA LEICHTLING, KD JACKSON, MO BLAESE, RM WEAVER, LD AF WINKELSTEIN, A HESS, RA LEICHTLING, KD JACKSON, MO BLAESE, RM WEAVER, LD TI INHIBITION OF HUMAN LYMPHOPROLIFERATIVE RESPONSES AND ALTERED LYMPHOCYTE MEMBRANE PHENOTYPE BY SUCCINYLACETONE SO IMMUNOPHARMACOLOGY LA English DT Article DE SUCCINYLACETONE; LYMPHOPROLIFERATIVE RESPONSE; IMMUNOSUPPRESSION; LYMPHOCYTE-T; LYMPHOCYTE PHENOTYPE; TRANSFERRIN RECEPTOR ID TRANSFERRIN RECEPTOR EXPRESSION; CYCLOSPORINE-A; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN-2 RECEPTOR; ORGAN-TRANSPLANTATION; CELL-PROLIFERATION; IRON-METABOLISM; T GROWTH; ACTIVATION; RETICULOCYTES AB Succinylacetone (SA) proved to be a potent inhibitor of in vitro lymphoproliferative responses. This compound (3.0 mM) reduced the incorporation of H-3Tdr by >90% in mononuclear cell cultures stimulated with PHA, anti-CD3, IL-2 or phorbol dibutyrate-Ca2+ ionomycin. Furthermore, SA caused profound reduction in isotope uptake even if added to 3-day PHA-stimulated cultures as late as 6 h prior to harvest. Cells exposed to SA prior to mitogenic challenge and washed were not impaired in their proliferative activities. The addition of hematin to SA-containing cultures did not reverse the proliferative block. Phenotypic studies of stimulated cells suggested that SA does not preferentially affect one functional group of lymphocytes. However, it appeared that SA may act selectively to inhibit expression of transferrin receptors (CD71), a T-cell activation antigen. These data suggest that SA acts as a noncytotoxic immune inhibitor; this activity may be mediated, in part, by blocking cell activation and subsequent progress through the mitotic cycle. C1 UNIV PITTSBURGH,SCH MED,DEPT MED,DIV HEMATOL BONE MARROW TRANSPLANT,PITTSBURGH,PA 15261. NCI,METAB BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-24429-17] NR 39 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD NOV-DEC PY 1992 VL 24 IS 3 BP 161 EP 170 DI 10.1016/0162-3109(92)90072-K PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA KE733 UT WOS:A1992KE73300001 PM 1478852 ER PT J AU WATSON, DC ROBBINS, JB SZU, SC AF WATSON, DC ROBBINS, JB SZU, SC TI PROTECTION OF MICE AGAINST SALMONELLA-TYPHIMURIUM WITH AN O-SPECIFIC POLYSACCHARIDE-PROTEIN CONJUGATE VACCINE SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; MONOCLONAL-ANTIBODIES; SEROGROUP-A; IMMUNOGENICITY; BACTEREMIA; OLIGOSACCHARIDE; CHILDREN; ANTIGEN; MOUSE; LIPOPOLYSACCHARIDES AB Serious infections with salmonellae remain a threat in many human populations. Despite extensive study of salmonella infections in animals and clinical experience with killed cellular vaccines, there are no vaccines against serotypes other than Salmonella typhi licensed for human use. Serum antibodies to the 0-specific polysaccharide (0-SP) of salmonellae protect mice against invasive infection. In order to render it immunogenic, we have conjugated the O-SP of Salmonella typhimurium to carrier proteins by various schemes. O-SP conjugated to tetanus toxoid (0-SP-TT) elicited antibodies in outbred mice after three subcutaneous injections without adjuvant. The O-SP alone elicited no detectable antibody. The antibody response to O-SP-TT was boosted by successive doses and consisted of immunoglobulin G (IgG) and IgM. Most mice only produced antibodies specific for the abequose (0:4 factor) region of the O-SP. Occasional animals also produced antibodies to the core oligosaccharide. Immunized mice were protected against intraperitoneal challenge with S. typhimurium, demonstrating a 160-fold increase in the 50% lethal dose. Passive immunization with conjugate-induced IgM or IgG also protected against challenge. These results indicate that an O-SP-TT conjugate, when given by a route and formulation acceptable for human use, protects mice against challenge with S. typhimurium. C1 NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 12557] NR 50 TC 59 Z9 59 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 NOV PY 1992 VL 60 IS 11 BP 4679 EP 4686 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JV763 UT WOS:A1992JV76300032 PM 1383154 ER PT J AU KONKEL, ME CIEPLAK, W AF KONKEL, ME CIEPLAK, W TI ALTERED SYNTHETIC RESPONSE OF CAMPYLOBACTER-JEJUNI TO COCULTIVATION WITH HUMAN EPITHELIAL-CELLS IS ASSOCIATED WITH ENHANCED INTERNALIZATION SO INFECTION AND IMMUNITY LA English DT Note ID NEISSERIA-GONORRHOEAE; HELA-CELLS; ENTERITIS; PROTEINS; INVASION; SALMONELLA; INFECTION; ADHESION; PENETRATION; ABILITY AB Campylobacter jejuni has been shown to bind to and enter epithelial cells in culture. The interaction of C. jejuni with INT 407 epithelial cells was examined to determine whether bacterial protein synthesis is required for either binding or internalization. Chloramphenicol, a selective inhibitor of bacterial protein synthesis, significantly reduced the internalization, but not binding, of C. jejuni compared with untreated controls as determined by protection from gentamicin. Electrophoretic analysis of metabolically labeled proteins revealed that C.jejuni cultured with INT 407 cells synthesized 14 proteins that were not detected in organisms cultured in medium alone. The inhibitory effect of chloramphenicol on internalization was reduced by preincubation of C. jejuni with INT 407 cells. The results indicate that C. jejuni, like some other enteric pathogens, engages in a directed response to cocultivation with epithelial cells by synthesizing one or more proteins that facilitate internalization and suggest that this phenomenon is relevant to the pathogenesis of enteritis caused by C. jejuni. RP KONKEL, ME (reprint author), NIAID,ROCKY MTN LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 33 TC 66 Z9 67 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 NOV PY 1992 VL 60 IS 11 BP 4945 EP 4949 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JV763 UT WOS:A1992JV76300066 PM 1399005 ER PT J AU GRABER, M JUNE, CH SAMELSON, LE WEISS, A AF GRABER, M JUNE, CH SAMELSON, LE WEISS, A TI THE PROTEIN TYROSINE KINASE INHIBITOR HERBIMYCIN-A, BUT NOT GENISTEIN, SPECIFICALLY INHIBITS SIGNAL TRANSDUCTION BY THE T-CELL ANTIGEN RECEPTOR SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE GENISTEIN; HERBIMYCIN-A; T-CELL ANTIGEN RECEPTOR ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; PHOSPHATIDYL-INOSITOL PATHWAY; PHOSPHOLIPASE-C; V-SRC; BIOCHEMICAL-CHARACTERIZATION; TOPOISOMERASE-II; RABBIT PLATELETS; IL-2 SECRETION; ALPHA-SUBUNITS; NIH-3T3 CELLS AB Several lines of evidence implicate a regulatory tyrosine phosphorylation in the activation of phospholipase C (PLC) by the T cell antigen receptor (TCR). These include studies using inhibitors of protein tyrosine kinases (PTKs). In Jurkat T cells expressing the heterologous human muscarinic receptor (HM1), PLC activity can be induced by either the TCR or HM1. HM1 activates PLC via a guanine nucleotide binding protein. We have studied the selectivity of the effects of the PTK inhibitors, herbimycin A and genistein, in this system. The results indicate that these inhibitors have different mechanisms of action, and suggest that herbimycin A, but not genistein, is a specific inhibitor of PTKs in T cells. Herbimycin A markedly inhibited both the resting and induced levels of phosphotyrosine-containing proteins, including the gamma1 isozyme of PLC and the zeta chain of the TCR, and prevented activation of PLC by anti-TCR mAb. Herbimycin A did not inhibit activation of PLC by HM1. Genistein had a much less pronounced effect than herbimycin A on the appearance of tyrosine phosphoproteins. Moreover, genistein inhibited activation of PLC by both the TCR and HM1, and inhibition was only partial. Genistein was cytotoxic and markedly inhibited protein synthesis in both Jurkat cells and human peripheral lymphocytes. Herbimycin A was not cytotoxic. These findings confirm the role of a regulatory tyrosine phosphorylation in activation of PLC by the TCR. Herbimycin A was a selective inhibitor of a subclass of PTKs in Jurkat cells. In contrast, inhibition of signal transduction and later events in T cells by genistein may be due to effects other than direct inhibition of PTK activity. C1 UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT IMMUNOL,SAN FRANCISCO,CA 94143. USN,MED RES CTR,BETHESDA,MD 20814. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP GRABER, M (reprint author), UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143, USA. FU NIDDK NIH HHS [K 11 DK01945-01] NR 64 TC 59 Z9 59 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 1992 VL 4 IS 11 BP 1201 EP 1210 DI 10.1093/intimm/4.11.1201 PG 10 WC Immunology SC Immunology GA JZ112 UT WOS:A1992JZ11200001 PM 1472473 ER PT J AU SAROSI, GA THOMAS, PM EGERTON, M PHILLIPS, AF KIM, KW BONVINI, E SAMELSON, LE AF SAROSI, GA THOMAS, PM EGERTON, M PHILLIPS, AF KIM, KW BONVINI, E SAMELSON, LE TI CHARACTERIZATION OF THE T-CELL ANTIGEN RECEPTOR-P60FYN PROTEIN TYROSINE KINASE ASSOCIATION BY CHEMICAL CROSS-LINKING SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE DIGITONIN; PHOSPHORYLATION; SIGNAL TRANSDUCTION ID PHOSPHOLIPASE C-GAMMA-1; SIGNAL TRANSDUCTION; CD4 RECEPTOR; MONOCLONAL-ANTIBODIES; ZETA-CHAIN; PHOSPHORYLATION; ACTIVATION; P56LCK; STIMULATION AB Engagement of the TCR by specific antigen results in activation of a tyrosine kinase pathway. A candidate for the kinase responsible for the rapid tyrosine phosphorylation detected with T cell activation is p60fyn, a member of the src kinase family. In an earlier study [Samelson et al. (1990) Proc. Natl Acad. Sci. USA 87:43581 this enzyme was co-immunoprecipitated with the TCR from T cells solubilized in digitonin. In that study a sensitive in vitro kinase assay was used to detect the associated p60fyn. It was subsequently found that the reproducibility of the interaction depended on lot-to-lot variations in digitonin. To eliminate the possibility that the association of antigen receptor and kinase is an artifact of solubilization with ill-defined digitonin preparations, a cross-linking protocol was developed to stabilize the interaction between the TCR and p60fyn. T cells were permeabilized with tetanolysin and proteins were cross-linked with the water soluble chemical cross-linker, 3,3' dithiobis(sulfosuccinimidylpropionate). These experiments allowed the confirmation of the interaction between the TCR, p60fyn, and several additional proteins. The cross-linking studies also enabled the mapping of the interaction of p60fyn and associated proteins to the TCR zeta-chain. This technique should have a general use in stabilizing interactions between other receptors and molecules required for intracellular signaling. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. FDA,CBER,CELL BIOL LAB,BETHESDA,MD 20892. NR 44 TC 42 Z9 42 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 1992 VL 4 IS 11 BP 1211 EP 1217 DI 10.1093/intimm/4.11.1211 PG 7 WC Immunology SC Immunology GA JZ112 UT WOS:A1992JZ11200002 PM 1472474 ER PT J AU GERACIOTI, TD GOLD, PW AF GERACIOTI, TD GOLD, PW TI OSCILLATORY INSTABILITY OF BODY-WEIGHT IN ALTERNATING ANOREXIA-NERVOSA AND BULIMIA-NERVOSA SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID TWINS AB The present study was undertaken to clarify the longitudinal course, from adolescence to the age of 40, of weight fluctuations in a woman with alternating anorexia nervosa and bulimia nervosa. Although it has long been appreciated that a single person may fluctuate between states of binge eating and obesity on the one hand, and starvation on the other, few data exist regarding the nature and mechanism of this interrelationship. As opposed to the gradual linear increase in weight normally observed in human beings from early adulthood through middle-age, our patient with alternating bulimia nervosa and anorexia nervosa showed chronic weight oscillation of great magnitude. However, her weight oscillations were periodic, as opposed to chaotic, and oscillated around her ideal body weight of 137 pounds. Moreover, the frequency of major weight changes increased with time. It is possible that a fundamental dysregulation of the hypothalamic feeding apparatus, wherein the normal homeostatic system loses its stability so that periodic oscillatory behavior results, unites the syndromes of anorexia and bulimia nervosa in the same individual. Finally, the pathological weight dynamics observed in this case show similarities to the phenomenology and course of bipolar affective disorders. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP GERACIOTI, TD (reprint author), VANDERBILT UNIV, MED CTR,SCH MED,DEPT PSYCHIAT,MED CTR N, RM A-2215, NASHVILLE, TN 37232 USA. NR 15 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 1992 VL 12 IS 3 BP 301 EP 306 DI 10.1002/1098-108X(199211)12:3<301::AID-EAT2260120310>3.0.CO;2-P PG 6 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA JV991 UT WOS:A1992JV99100009 ER PT J AU BLACK, PL HARTMANN, D PENNINGTON, R PHILLIPS, H SCHNEIDER, M TRIBBLE, HR TALMADGE, JE AF BLACK, PL HARTMANN, D PENNINGTON, R PHILLIPS, H SCHNEIDER, M TRIBBLE, HR TALMADGE, JE TI EFFECT OF TUMOR BURDEN AND ROUTE OF ADMINISTRATION ON THE IMMUNOTHERAPEUTIC PROPERTIES OF POLYINOSINIC POLYCYTIDYLIC ACID STABILIZED WITH POLY-L-LYSINE IN CARBOXYMETHYL CELLULOSE [POLY(I,C)-LC] SO INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY LA English DT Article ID MURINE OSTEOGENIC-SARCOMA; KILLER CELL ACTIVITY; I-C; INTERFERON INDUCERS; CANCER-PATIENTS; MICE; POLYRIBONUCLEOTIDES; AUGMENTATION; MACROPHAGES; METASTASIS AB We examined the immunomodulatory and therapeutic activities of poly(I,C) - LC. Mice received a subcutaneous (s.c.) injection of sufficient numbers of MBL-2 lymphoma cells to produce in 1 week either a high or low tumor burden. A week after tumor cell injection, poly(I,C) - LC treatment was initiated; the agent was administered intraperitoneally (i.p.) at 5 mg/kg twice a week or at 2.5 or 0.5 mg/kg every day or as an intravenous (i.v.) injection at 0.5, 0.05, or 0.005 mg/kg three times a week. Poly(I,C) - LC treatment significantly increased antitumor effector cell functions in a variety of organs (including spleen, lungs, and peritoneum), as shown by increased killing of MBL-2 cells in vitro and increased tumor cell killing by natural killer cells and macrophages. Furthermore, prolongation of survival correlated with peritoneal macrophage tumoricidal activity when poly(I,C) - LC was given i.p. and with pulmonary effector cell function (including natural killer, cytolytic T-lymphocyte and macrophage tumoricidal activity) when the agent was administered i.v. C1 NIPPON LAROCHE,KANAGAWA 247,JAPAN. NIH,FREDERICK CANC RES,PRECLIN SCREENING LAB,FREDERICK,MD 21702. SMITHKLINE BEECHAM PHARMACEUT,KING OF PRUSSIA,PA 19406. UNIV NEBRASKA,MED CTR,OMAHA,NE 68198. RP BLACK, PL (reprint author), US FDA,DIV ANTIVIRAL DRUG PROD,HFD 530,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. RI Talmadge, James/A-5916-2008 OI Talmadge, James/0000-0002-6328-6056 FU PHS HHS [N01-23910] NR 59 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0192-0561 J9 INT J IMMUNOPHARMACO JI Int. J. Immunopharmacol. PD NOV PY 1992 VL 14 IS 8 BP 1341 EP 1353 DI 10.1016/0192-0561(92)90005-6 PG 13 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA JZ257 UT WOS:A1992JZ25700005 PM 1464467 ER PT J AU PRICE, RA LUNETTA, K NESS, R CHARLES, MA SAAD, MF RAVUSSIN, E BENNETT, PH PETTITT, DJ KNOWLER, WC AF PRICE, RA LUNETTA, K NESS, R CHARLES, MA SAAD, MF RAVUSSIN, E BENNETT, PH PETTITT, DJ KNOWLER, WC TI OBESITY IN PIMA-INDIANS - DISTRIBUTION CHARACTERISTICS AND POSSIBLE THRESHOLDS FOR GENETIC-STUDIES SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE BODY MASS INDEX; COMMINGLING ANALYSIS; DISTRIBUTIONS; GENETICS; PIMA INDIANS ID EXTREME OVERWEIGHT; DIABETES INCIDENCE; WOMEN; INHERITANCE; PREVALENCE; FAMILIES; MEN AB We examined distribution characteristics of the body mass index (BMI; weight/height2; kg/m2) in a sample of 1128 male and 1372 female Pima Indians aged 15-65 years. We found that women had a higher mean and variance of BMI than men. From commingling analyses, we determined that the distribution of BMI could be accounted for either by a single skewed distribution or by a mixture of multiple normal components. These component distributions may be used to define provisional thresholds in selecting families for genetic studies. To ensure genetic segregation of obesity predisposing genes in Pima families will require that some members have BMIs greater-than-or-equal-to 40 kg/m2. C1 NIDDKD,PHOENIX,AZ. RP PRICE, RA (reprint author), UNIV PENN,SCH MED,DEPT PSYCHIAT,422 CURIE BLVD,CRB-145B,PHILADELPHIA,PA 19104, USA. FU NCI NIH HHS [CA09529]; NIDDK NIH HHS [DK44073]; NIMH NIH HHS [MH43409] NR 19 TC 9 Z9 9 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 1992 VL 16 IS 11 BP 851 EP 857 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA JW697 UT WOS:A1992JW69700002 PM 1337339 ER PT J AU ASCIONE, R THOMPSON, DM THOMAS, R PANAYIOTAKIS, A RAMSAY, R TYMMS, M KOLA, I SETH, A AF ASCIONE, R THOMPSON, DM THOMAS, R PANAYIOTAKIS, A RAMSAY, R TYMMS, M KOLA, I SETH, A TI INFLUENCE OF NUCLEOTIDES FLANKING THE GGAA CORE SEQUENCE ON ETS1 AND ETS2 DNA-BINDING ACTIVITY AND THE MECHANISM OF ETS1 AUTOREGULATION SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ETS FAMILY GENES; DNA BINDING; MECHANISM OF ETS1 AUTOREGULATION ID LONG TERMINAL REPEAT; T-CELL; C-ETS-1 PROTOONCOGENE; CHROMOSOMAL GENE; LEUKEMIA-VIRUS; B-CELL; PROTEIN; TRANSCRIPTION; ACTIVATION; EXPRESSION AB The Ets family of genes encode nuclear proteins that activate transcription by binding to a specific purine-rich (GGAA) ets binding sequence (EBS) present in promoters/enhancers of various genes. We have previously shown that over-expression of ets1 via transfection of ets1 expression vectors into NIH3T3 cells induced the expression of the endogenous Ets1 gene. Here we report that the autoregulation occurs as a result of the ets1 protein binding to the EBS-core located in its own promoter. In the present study, we have also identified Ets binding sites in the IL-4, G-CSF (granulocyte colony stimulating factor), and the 2'5' OAS (oligoadenylate synthetase) promoters by binding with Ets1 and Ets2 proteins using electrophoretic mobility shift assays. Interestingly, we have found that the EBS containing T nucleotides on either side of the GGAA core sequence, does not bind Ets1 or Ets2 proteins. Our findings demonstrate that the sequences surrounding the purine core - GGAA- have a profound influence on the binding of Ets proteins. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. LUDWIG INST CANC RES,MELBOURNE TUMOR BIOL BRANCH,MELBOURNE,VIC,AUSTRALIA. MONASH UNIV,CTR EARLY HUMAN DEV,MOLEC EMBRYOL & BIRTH DEFECT LAB,CLAYTON,VIC 3168,AUSTRALIA. RI Thomas, Ross/C-6434-2008; Kola, Ismail/C-5254-2013 NR 29 TC 25 Z9 25 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 1992 VL 1 IS 6 BP 631 EP 637 PG 7 WC Oncology SC Oncology GA JV123 UT WOS:A1992JV12300004 PM 21584592 ER PT J AU DIMITROV, NV BENNETT, JL MCMILLAN, J PERLOFF, M LEECE, CM MALONE, W AF DIMITROV, NV BENNETT, JL MCMILLAN, J PERLOFF, M LEECE, CM MALONE, W TI CLINICAL-PHARMACOLOGY STUDIES OF OLTIPRAZ - A POTENTIAL CHEMOPREVENTIVE AGENT SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE OLTIPRAZ; CHEMOPREVENTION; DITHIOLETHIONES; PHARMACOKINETICS; TOXICITY ID SCHISTOSOMA-MANSONI; 5-(2-PYRAZINYL)-4-METHYL-1,2-DITHIOL-3-THIONE OLTIPRAZ; CARCINOGENESIS; TRIALS; BLOOD; RATS AB Pharmacological studies on Oltipraz [4-methyl-5(pyrazinyl-2)-1-2-dithiole-3-thione)] were conducted with normal healthy subjects using various doses and schedules. Administration of single doses (1, 2 and 3 mg/kg) resulted in detectable drug levels in the serum (mean peak serum concentrations 16, 61 and 205 ng, respectively) and urine. The t1/2 was short (4.4, 4.1 and 5.3 hours respectively) and no steady state was achieved after multiple daily doses for 12 days. Introduction of a loading dose during the first day produced a steady state when 1.5 and 2.0 mg/kg/day were used. Daily administration of Oltipraz sustained the steady state with insignificant variations. Consumption of a high fat diet increased the serum and urine concentrations of Oltipraz (30-60%) compared to the low fat diet. Two subjects experienced flatulence during the administration of the drug. One subject developed numbness and pain in the thumbs with occurrence of small purplish-black spots resembling those observed in subacute endocarditis. These changes disappeared 10 days after discontinuation of the drug. No changes in peripheral blood counts, biochemical profile or thyroid function tests were observed after four weeks of Oltipraz. Further studies with a larger number of healthy subjects are needed for clarification of the safety and biological efficacy of small doses of Oltipraz during chronic administration. C1 MICHIGAN STATE UNIV,DEPT PHARMACOL & TOXICOL,E LANSING,MI 48824. NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. RP DIMITROV, NV (reprint author), MICHIGAN STATE UNIV,DEPT MED,B-220 LIFE SCI BLDG,E LANSING,MI 48824, USA. FU NCI NIH HHS [N01-CN-85104] NR 27 TC 32 Z9 32 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 1992 VL 10 IS 4 BP 289 EP 298 DI 10.1007/BF00944183 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA KF634 UT WOS:A1992KF63400007 PM 1487402 ER PT J AU YOU, WC BLOT, WJ CHANG, YS LI, JY JIN, ML ZHAO, YX KNELLER, RW XIE, YQ ZHANG, L XU, GW FRAUMENI, JF AF YOU, WC BLOT, WJ CHANG, YS LI, JY JIN, ML ZHAO, YX KNELLER, RW XIE, YQ ZHANG, L XU, GW FRAUMENI, JF TI COMPARISON OF THE ANATOMIC DISTRIBUTION OF STOMACH-CANCER AND PRECANCEROUS GASTRIC-LESIONS SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE STOMACH CANCER; PRECANCEROUS LESIONS; ANATOMIC DISTRIBUTION ID HIGH-RISK; POPULATION; CARCINOMA AB The anatomic distribution of precancerous gastric lesions among 3,400 residents in Linqu, Shandong Province of China, was compared with the anatomic distribution of stomach cancer (SC) among 959 patients in Tokyo, Japan. The incidence of SC is high in both areas, and locations within the stomach of the precancerous and malignant lesions were classified using similar criteria. Chronic atrophic gastritis (CAG) affected 98% of the population in Linqu, with intestinal metaplasia (IM) the most severe diagnosis in 33% and dysplasia (DYS) in 20%. Neither the SC nor precancerous lesions were uniformly distributed in the stomach. Among the DYS 3% were along the greater curvature of the body, 15% along the lesser curvature of the body, 25% in the angulus, 22% along the lesser curvature of the antrum, and 34% elsewhere in the antrum. Among the SC the corresponding percentages were 2, 16, 28, 25 and 29. The similarity to the SC distribution increased gradually from CAG to IM to DYS, providing further evidence for the multistage progression of precancerous gastric lesions. C1 NCI,BETHESDA,MD 20892. BEIJING INST CANC RES,BEIJING 100034,PEOPLES R CHINA. WEIFANG MED INST,WEIFANG 261041,PEOPLES R CHINA. LINQU CTY HOSP,LINQU 252600,PEOPLES R CHINA. FU NCI NIH HHS [N01-CP-05631, N01-CP-95660, N01-CP-15620] NR 22 TC 14 Z9 16 U1 0 U2 0 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 NOV PY 1992 VL 83 IS 11 BP 1150 EP 1153 PG 4 WC Oncology SC Oncology GA JZ834 UT WOS:A1992JZ83400010 PM 1483930 ER PT J AU OBATA, T YAMANAKA, Y CHIUEH, CC AF OBATA, T YAMANAKA, Y CHIUEH, CC TI INVIVO RELEASE OF DOPAMINE BY PERFUSION OF 1-METHYL-4-PHENYLPYRIDINIUM ION IN THE STRIATUM WITH A MICRODIALYSIS TECHNIQUE SO JAPANESE JOURNAL OF PHARMACOLOGY LA English DT Note DE 1-METHYL-4-PHENYLPYRIDINIUM ION (MPP+); MONOAMINE OXIDASE (B-FORM); PARKINSONISM ID BRAIN MONOAMINE-OXIDASE; RAT STRIATUM; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; METABOLISM; MPTP; MPP+; INHIBITION; SEROTONIN; DIALYSIS; NEUROTOXICITY AB We examined the effects of 1-methyl-4-phenylpyridinium ion (MPP+) on the release of DA in rat striatum by the in vivo microdialysis technique. For this study, we made a suitable microdialysis probe from a 22-G needle, microliter pipette tip, silica tube and polyethylene tube. Such a repairable microdialysis probe can be easily made from readily available and inexpensive materials. DA release, as determined by the 3-methoxytyramine level, was dose-dependently increased by MPP+ (1-10 mM). Only the presence of a 1 mM concentration of MPP+ in the dialysate significantly decreased the level of the DA metabolite DOPAC, while administration of higher MPP+ concentrations resulted in no significant change. C1 NIMH,BETHESDA,MD 20892. RP OBATA, T (reprint author), OITA MED UNIV,DEPT PHARMACOL,1-1 IDAIGAOKA,HAZAMA MACHI,OITA 87955,JAPAN. NR 13 TC 28 Z9 28 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO 604, JAPAN SN 0021-5198 J9 JPN J PHARMACOL JI Jpn. J. Pharmacol. PD NOV PY 1992 VL 60 IS 3 BP 311 EP 313 DI 10.1254/jjp.60.311 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KA727 UT WOS:A1992KA72700023 PM 1491520 ER PT J AU HULTON, MR LEVIN, DL FREEDMAN, LS AF HULTON, MR LEVIN, DL FREEDMAN, LS TI RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND-STUDY OF LOW-DOSE ORAL INTERFERON-ALPHA IN HIV-1 ANTIBODY POSITIVE PATIENTS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE RANDOMIZED CLINICAL TRIAL; HUMAN IMMUNODEFICIENCY VIRUS TYPE-1; ORAL ADMINISTRATION; THERAPY; INTERFERON-ALPHA; CD4 CELL COUNT; CANADA; TORONTO ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; KAPOSI-SARCOMA; AIDS; BETA-2-MICROGLOBULIN AB One hundred forty-nine patients of private physicians in Toronto, Canada, who were positive for human immunodeficiency virus (HIV), medically stable, and had CD4 cell counts of <700 cells/mm3 participated in a randomized, double-blind trial of placebo versus low-dose (50 U) versus high-dose (100 U) oral interferon-alpha. Treatment allocation was balanced according to baseline CD4 cell count and history of prior antiviral therapy. Patients were observed at 4 and 8 weeks for assessment of adverse events and several measures of disease status, including CD4 cell count, beta2-microglobulin, weight, and Karnofsky score. We detected neither short-term benefits nor adverse effects from oral interferon-alpha therapy. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892. COMMUNITY RES INITIAT TORONTO,TORONTO,ONTARIO,CANADA. NR 12 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD NOV PY 1992 VL 5 IS 11 BP 1084 EP 1090 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JV265 UT WOS:A1992JV26500004 PM 1357152 ER PT J AU PARK, LP MARGOLICK, JB GIORGI, JV FERBAS, J BAUER, K KASLOW, R MUNOZ, A AF PARK, LP MARGOLICK, JB GIORGI, JV FERBAS, J BAUER, K KASLOW, R MUNOZ, A TI INFLUENCE OF HIV-1 INFECTION AND CIGARETTE-SMOKING ON LEUKOCYTE PROFILES IN HOMOSEXUAL MEN SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; SEROCONVERSION; CIGARETTE SMOKING; WHITE BLOOD CELLS ID MULTICENTER AIDS COHORT; LYMPHOCYTE-T SUBSETS; ALLERGY; COUNT; CELLS AB The interaction between the effects of HIV-1 infection and cigarette smoking on leukocyte profiles was studied in 307 HIV-1 seroconverters in the Multicenter AIDS Cohort Study (MACS). Longitudinal data for white blood cell (WBC) counts, WBC differentials, T cell subsets, and smoking behavior were collected semiannually for up to 7 years. Prior to seroconversion, total WBC count increased in direct proportion to daily cigarette consumption, but this effect disappeared within 3 years of seroconversion. Analyses of WBC subsets (lymphocytes, monocytes, and granulocytes) and lymphocyte subsets (CD4+, CD8+ and non-T [CD3-]) showed that smoking had only minor effects on the proportions of these cells. In contrast, HIV-1 seroconversion was associated with a dramatic decrease in CD4+ lymphocyte percentage, a large increase in CD8+ lymphocyte percentage, a small increase in total lymphocyte percentage, and small decreases in the non-T lymphocyte and granulocyte percentages. These findings indicate that the effect of smoking on CD4 cell counts is (a) nonspecific, (b) maximal in seronegative individuals; and (c) lost by 3 years after seroconversion. Although the mechanism of the loss of smoking-induced leukocytosis after seroconversion remains to be determined, our results suggest that the effects of smoking are not likely to be important in the clinical use of leukocyte measurements, including measurements of CD4 lymphocytes, in individuals who have been HIV-1 seropositive for more than 3 years. C1 JOHNS HOPKINS SCH PUBL HLTH,DEPT EPIDEMIOL,624 N BROADWAY,BALTIMORE,MD 21205. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV PITTSBURGH,SCH PUBL HLTH,PITTSBURGH,PA 15260. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. NIAID,BETHESDA,MD 20892. OI Wolinsky, Steven/0000-0002-9625-6697 NR 19 TC 43 Z9 43 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 NOV PY 1992 VL 5 IS 11 BP 1124 EP 1130 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JV265 UT WOS:A1992JV26500011 PM 1403643 ER PT J AU KOHLER, H GOUDSMIT, J NARA, P AF KOHLER, H GOUDSMIT, J NARA, P TI CLONAL DOMINANCE - CAUSE FOR A LIMITED AND FAILING IMMUNE-RESPONSE TO HIV-1 INFECTION AND VACCINATION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE CLONAL DOMINANCE; ORIGINAL ANTIGENIC SIN; REPERTOIRE FREEZE; OLIGOCLONAL ANTIBODY POPULATION; CROSS-REACTIVE IMMUNODOMINANT EPITOPES; SHARED EPITOPES ID HUMAN-IMMUNODEFICIENCY-VIRUS; B-CELL ACTIVATION; HUMAN LYMPHOCYTES-B; NEUTRALIZING ANTIBODIES; CHIMPANZEES; BINDING; SERA; CD4; DETERMINANTS; IMMUNIZATION AB Oligoclonal and monoclonal antibody populations against different HIV-encoded proteins are common in sera from healthy HIV-1-infected individuals. This is especially important when it includes functional antibody repertoires directed at neutralizing cell free virus or inhibiting cell fusion of virus-infected cells. In the host, during the acute viral syndrome following HIV-1 infection, a rapidly replicating, cell-free and genotypically homogeneous viral population is known to arise from the transmitted viral inoculum. Dominant B and possibly T cell clones responsible for both functional and nonfunctional antibodies appear to arise early in response to this initially homogeneous cell-free viral population heralding seroconversion. During the viremic phase, deposition of cell-free virus as either complement coated or as immune complexes (iccosomes) within the germinal centers results in continued and long-term boosting of primed B cells. This saturation of antigen presenting germinal centers and the presence of limited, immunodominant cross-reactive epitopes on the envelope glycoprotein of the closely-related and immune selected viral quasispecies in the host appear to continue the boosting effect of the primed secondary response. This repertoire freeze appears to be responsible for limiting the recruitment of new uncommitted B cells to other functional epitopes or affinity maturation of B-cell clones to escape variants and the subsequent production and quality of functional antibody against the evolving/selected virus populations. This may include in addition to neutralizing and cell fusion inhibiting antibody, direct complement-fixing and/or NK-directed antibody-dependent cell-mediated antibody as well as various effector, helper, or T cell-mediated activity. In addition to antiviral antibody responses, antibody directed to other invading pathogens or opportunistic organisms may also be clonaly restricted. Antibody facilitating infectivity or blocking effective immunity may also be included in this phenomena and thus be over represented by such a mechanism. AIDS vaccines utilizing the envelope must identify these epitopes to avoid creating clonal dominance and therefore possibly limit the breadth and specificity of a humoral response following infection. Furthermore, immunotherapeutic approaches designed to recruit humoral immune effector function must be able to overcome the dominance of noneffective antibodies and restore a normal polyclonal immune response against HIV. Further research, therefore, into the humoral and cellular dysregulating properties of the HIV-1 envelope is warranted. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,TUMOR CELL BIOL LAB,FREDERICK,MD 21701. SAN DIEGO REG CANC CTR,SAN DIEGO,CA. UNIV AMSTERDAM,AMSTERDAM,NETHERLANDS. NR 80 TC 49 Z9 49 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 NOV PY 1992 VL 5 IS 11 BP 1158 EP 1168 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JV265 UT WOS:A1992JV26500016 PM 1403647 ER PT J AU LEIBENLUFT, E NOONAN, BM WEHR, TA AF LEIBENLUFT, E NOONAN, BM WEHR, TA TI DIURNAL-VARIATION - RELIABILITY OF MEASUREMENT AND RELATIONSHIP TO TYPICAL AND ATYPICAL SYMPTOMS OF DEPRESSION SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE DIURNAL VARIATION; ATYPICAL DEPRESSION; TYPICAL DEPRESSION ID PRIMARY AFFECTIVE-DISORDER; MOOD; RHYTHM AB We used three rating scales to study diurnal variation of mood in 37 patients with major depressive disorder (17 drug-free patients and 20 treatment refractory patients on stable regimens of antidepressant medication). The three rating scales included global self-ratings administered twice a day; an itemized, prospective, observer-rated scale administered twice a day; and the retrospective item on the Hamilton Depression Rating Scale. Z scores and Intraclass Correlation Coefficients demonstrated a poor level of agreement between the itemized, prospective scale and the self-ratings. In addition, stepwise multiple regression analysis and point bi-serial correlation showed no systematic relationship between atypical diurnal variation (i.e., mood worsening in the evening) and atypical depressive symptoms (weight gain, hypersomnia, etc.), or between typical diurnal variation (i.e., mood worsening in the morning) and typical depressive symptoms (weight loss, insomnia, etc.). This lack of relationship was observed in both drug-free and medicated patients using each of the three rating scales. We discuss possible explanations for these negative findings. RP LEIBENLUFT, E (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 4S239,BETHESDA,MD 20892, USA. NR 20 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 1992 VL 26 IS 3 BP 199 EP 204 DI 10.1016/0165-0327(92)90016-Y PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KB755 UT WOS:A1992KB75500008 PM 1460170 ER PT J AU IRWIN, PL SEVILLA, MD CHAMULITRAT, W HOFFMAN, AE KLEIN, J AF IRWIN, PL SEVILLA, MD CHAMULITRAT, W HOFFMAN, AE KLEIN, J TI LOCALIZED, INTERNAL, AND SUPRAMOLECULAR POLYURONIDE MOTIONS IN CELL-WALL MATRICES - A COMPARISON OF SOLID-STATE NMR AND EPR RELAXATION BEHAVIOR SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article ID HOMOPOLYGALACTURONAN NITROXYL AMIDES; FRUIT CORTICAL TISSUE; SPECTROSCOPIC EVIDENCE; PARAMAGNETIC ION; CARBOXYL GROUPS; APPLE; PERTURBATIONS; SIZE AB Previous work has revealed that spin-labeled cell wall homopolygalacturonans display internal motions predominantly about the polymer's main chain. In this work we show that the nitroxyl amide's relaxation behavior is modulated by these same motions. Polyuronide-bound Na-23+ spin-lattice relaxation times as well as C-13=O rotating frame T1s, which are tempered by the local carboxyl group environment, of non-spin-labeled, but otherwise identical, apple tissue manifested a 15-19% decrement as a function of differing levels of tissue ripeness. Similarly, a higher-order or supramolecularly averaged measure of cell wall polyuronide motion, C=O-associated T1H, declined 63% with tissue ripeness. In paramagnetically labeled treatments the nitroxyl amide's relaxation parameter diminished ca. 49%. The scope of these molecular level perturbations follows the order local < internal < supramolecular and argue that the changes in polygalacturonan flexibility associated with ripening result from processes other than the cleavage of the polyuronide backbone. C1 OAKLAND UNIV,DEPT CHEM,ROCHESTER,MI 48063. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. VOLCANI CTR,DEPT FIELD CROPS,BET DAGAN,ISRAEL. RP IRWIN, PL (reprint author), USDA ARS,EASTERN REG RES CTR,600 E MERMAID LANE,PHILADELPHIA,PA 19118, USA. NR 41 TC 8 Z9 8 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD NOV PY 1992 VL 40 IS 11 BP 2045 EP 2051 DI 10.1021/jf00023a003 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA JZ340 UT WOS:A1992JZ34000003 ER PT J AU EMERY, BE WHITE, MV IGARASHI, Y MULLOL, J BERKEBILE, C PEDEN, D LOTZE, MT KALINER, MA AF EMERY, BE WHITE, MV IGARASHI, Y MULLOL, J BERKEBILE, C PEDEN, D LOTZE, MT KALINER, MA TI THE EFFECT OF IL-4 ON HUMAN NASAL MUCOSAL RESPONSES SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE NASAL CONGESTION; IL-4; CANCER NASAL CHALLENGE ID PATHO-PHYSIOLOGY; HISTAMINE TACHYPHYLAXIS; INTERLEUKIN-4 PROMOTES; RHINITIS; SECRETIONS; LYMPHOCYTES; PROTEIN; GROWTH; DOGS AB Interleukin (IL)-4 causes the dose limiting sensation of nasal congestion when administered systemically at doses of 3 mug/kg or higher thrice daily to humans. This side effect was observed in a group of patients treated as part of an immunotherapy protocol for cancer management. To determine the source of this congestion, nasal secretions were collected prospectively in a group of patients at baseline and after provocation with normal saline, methacholine (which stimulates glandular secretion), and histamine (which causes increased vascular permeability). Nasal lavages obtained at baseline and after provocation were analyzed for the presence of these glandular and vascular proteins and inflammatory mediators. Washings and provocations were performed before IL-4 administration, after 24 hours of IL-4 treatment, and after 3 days of treatment, at a time when nasal congestion was maximal. Compared with histamine challenge before IL-4 treatment, the secretion of the plasma proteins albumin and IgG were significantly decreased after 3 days of IL-4 treatment. IL-4 treatment had no apparent effect on methacholine-induced responses. Thus systemically administered IL-4 causes the subjective sensation of nasal congestion, increased histamine in nasal lavages, and the development of vascular unresponsiveness to histamine, without affecting parasympathetic responses to histamine. The relationships among increases in nasal lavage histamine, vascular unresponsiveness to histamine, and the sensation of nasal congestion are unclear. C1 LOUISIANA STATE UNIV,DEPT OTOLARYNGOL HEAD & NECK SURG,SHREVEPORT,LA 71105. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,CTR CLIN,INTENS CARE UNIT,BETHESDA,MD 20892. UNIV PITTSBURGH,MED CTR,PITTSBURGH CANC INST,PITTSBURGH,PA 15260. NR 31 TC 15 Z9 15 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 1992 VL 90 IS 5 BP 772 EP 781 DI 10.1016/0091-6749(92)90101-7 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA JZ319 UT WOS:A1992JZ31900007 PM 1430703 ER PT J AU MICAN, JAM ARORA, N BURD, PR METCALFE, DD AF MICAN, JAM ARORA, N BURD, PR METCALFE, DD TI PASSIVE CUTANEOUS ANAPHYLAXIS IN MOUSE SKIN IS ASSOCIATED WITH LOCAL ACCUMULATION OF INTERLEUKIN-6 MESSENGER-RNA AND IMMUNOREACTIVE INTERLEUKIN-6 PROTEIN SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE MAST CELL; IGE; MURINE; SKIN; IL-6; ALLERGY; IMMEDIATE HYPERSENSITIVITY ID TUMOR-NECROSIS-FACTOR; MACROPHAGE INFLAMMATORY PROTEIN-1; FC-EPSILON-RI; MAST-CELLS; FACTOR-ALPHA; LATE PHASE; IGE; IL-6; EXPRESSION; CYTOKINES AB We used a BALB/c model of passive cutaneous anapkylaxis (PCA), an IgE-mediated, mast cell-dependent reaction, to demonstrate the early production of the proinflammatory cytokine interleukin-6 (IL-6) mRNA and protein product. Northern blot analysis detects IL-6 mRNA 1, and 2 hours after antigen challenge (dinitrophenyl30-40 human serum albumin [DNP30-40-HSA]) and in situ hybridization reveals that it is primarily cells with round-to-oval nuclei within the dermis (1 to 3 per high-power field) expressing IL-6 mRNA. Immunohistochemistry revealed perinuclear and cytoplasmic staining for immunoreactive IL-6 in mononuclear dermal cells and also cells within the basal keratinocyte layer. Injection of recombinant murine IL-6 (rmIL-6) either systemically or locally during antidinitrophenyl IgE skin sensitization resulted in increased vasopermeability at the PCA site after DNP30-40-HSA. However, this increased permeabiliiy was not associated with a change in the character of the cellular infiltrate at the PCA site 8 hours later. Although the specific role of IL-6 in the generation of the allergic response remains unknown, its detection during PCA unequivocally demonstrates that IL-6 be considered one of the mediators identified in inflammation that follows allergic reactions. RP MICAN, JAM (reprint author), NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BLDG 10 2C410,BETHESDA,MD 20892, USA. NR 44 TC 73 Z9 74 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 1992 VL 90 IS 5 BP 815 EP 824 DI 10.1016/0091-6749(92)90107-D PG 10 WC Allergy; Immunology SC Allergy; Immunology GA JZ319 UT WOS:A1992JZ31900013 PM 1430707 ER PT J AU YUAN, JH BUCHER, JR GOEHL, TJ DIETER, MP JAMESON, CW AF YUAN, JH BUCHER, JR GOEHL, TJ DIETER, MP JAMESON, CW TI QUANTITATION OF CINNAMALDEHYDE AND CINNAMIC ACID IN BLOOD BY HPLC SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID RAT RP YUAN, JH (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 9 TC 18 Z9 25 U1 0 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD NOV-DEC PY 1992 VL 16 IS 6 BP 359 EP 362 PG 4 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA JZ331 UT WOS:A1992JZ33100004 PM 1293401 ER PT J AU CONE, EJ AF CONE, EJ TI CONCERNING NORCOCAINE, ETHYLBENZOYLECGONINE, AND THE IDENTIFICATION OF COCAINE USE IN HUMAN HAIR - REPLY SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Letter RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD NOV-DEC PY 1992 VL 16 IS 6 BP 402 EP 402 PG 1 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA JZ331 UT WOS:A1992JZ33100014 ER PT J AU BARANIUK, JN SILVER, PB KALINER, MA BARNES, PJ AF BARANIUK, JN SILVER, PB KALINER, MA BARNES, PJ TI NEUROPEPTIDE-Y IS A VASOCONSTRICTOR IN HUMAN NASAL-MUCOSA SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE BRADYKININ; NASAL SECRETION; ALBUMIN; VASCULAR PERMEABILITY; MUCOSAL BLOOD FLOW; SYMPATHETIC NERVOUS SYSTEM; GLYCOCONJUGATES; NEUROGENIC INFLAMMATION ID GUINEA-PIG AIRWAYS; PATHO-PHYSIOLOGY; PLASMA EXUDATION; BRADYKININ; SECRETION; RHINITIS; INVIVO; CAPSAICIN; PROTEIN; KININS AB Neuropeptide Y (NPY) is a neurotransmitter in sympathetic nerve fibers in human nasal mucosa. Like norepinephrine, NPY acts as a vasoconstrictor. An established method of nasal provocation was used to determine the effects of topically applied NPY on nasal resistance to airflow measured by anterior rhinomanometry, the protein content of nasal secretions, and the protein content of bradykinin-induced secretions. NPY (2.3 nmol) reduced the resistance to inspiratory airflow by 57 +/- 18% (P < 0.001) in 10 normal subjects and by 50 +/- 17% (P < 0.05) in 12 subjects with perennial rhinitis. In nasal provocations, NPY in doses of 0.1-10 nmol had no effect on vascular (albumin), glandular (lysozyme, glycoconjugate), or total proteins present in lavaged nasal secretions. Because the vasoconstrictor properties of NPY may only be apparent in the presence of increased vascular permeability and albumin exudation, bradykinin (BK) nasal provocation was performed. BK (500 nmol) significantly increased total protein (10- to 20-fold), albumin (10- to 30-fold), and glycoconjugate (2- to 5-fold) in lavage fluid. NPY (2.3 nmol) reduced BK-induced total protein by 59 +/- 15% (P < 0.05) and albumin by 63 +/- 17% (P < 0.02) but had no significant effect on glandular secretion. Therefore exogenous administration of NPY to the human nasal mucosa reduced nasal airflow resistance and albumin exudation without affecting submucosal gland secretion. NPY agonists may be useful for the treatment of mucosal diseases characterized by vasodilation, vascular permeability, and plasma exudation. C1 NIAID,ALLERG DIS SECT,BETHESDA,MD 20892. NATL HEART & LUNG INST,LONDON SW3 6LY,ENGLAND. RP BARANIUK, JN (reprint author), GEORGETOWN UNIV,DEPT MED,GL-020 GORMAN BLDG,3800 RESERVOIR RD,WASHINGTON,DC 20007, USA. NR 37 TC 31 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1992 VL 73 IS 5 BP 1867 EP 1872 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA JZ596 UT WOS:A1992JZ59600027 PM 1282125 ER PT J AU MULLOL, J BARANIUK, JN LOGUN, C MERIDA, M HAUSFELD, J SHELHAMER, JH KALINER, MA AF MULLOL, J BARANIUK, JN LOGUN, C MERIDA, M HAUSFELD, J SHELHAMER, JH KALINER, MA TI M1 AND M3 MUSCARINIC ANTAGONISTS INHIBIT HUMAN NASAL GLANDULAR SECRETION INVITRO SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE PIRENZEPINE; GALLAMINE; AF-DX 116; 4-DIPHENYLACETOXY-N-METHYLPIPERIDINE METHIODIDE; MUCIN; MUCOSAL SECRETION; MUSCARINIC RECEPTOR SUBTYPES; HUMAN NASAL MUCOSA ID GUINEA-PIG LUNG; RECEPTOR SUBTYPES; PIRENZEPINE; AIRWAYS; MUCOSA; GALLAMINE; MEMBRANES; BINDING; PROFILE; BRAIN AB Mucus glycoproteins (MGP) are high-molecular-weight glycoconjugates that are released from submucosal glands and epithelial goblet cells in the respiratory tract. Muscarinic receptors have an important role in the regulation of human nasal glandular secretion and mucus production, but it is not known which of the five muscarinic receptor subtypes are involved. The effect of nonselective and M1-, M2-, and M3-selective muscarinic antagonists on methacholine (MCh)-induced MGP secretion from human nasal mucosal explants was tested in vitro. MGP was assayed by enzyme-linked immunosorbent assay using a specific anti-MGP monoclonal antibody (7F10). MCh (100 muM) induced MGP secretion up to 127% compared with controls. MCh-induced MGP release was significantly inhibited by atropine (100 muM), the M, receptor antagonist pirenzepine (10-100 AM), and the M3 receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; 1-100 muM). 4-DAMP significantly inhibited MCh-induced MGP release at a lower concentration (1 muM) than pirenzepine (10 muM). The M2 receptor antagonists AF-DX 116 and gallamine (both at 100 muM) had no effect. No antagonist alone had a significant effect on MGP release. These results indicate that the M1 and M2 muscarinic receptor subtypes regulate MGP secretion from human nasal mucosa and suggest that the M3 receptor has the predominant effect. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,RM 11-C-205,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. HOSP CLIN BARCELONA,SERV PNEUMOL & ALLERGIA RESP,E-08036 BARCELONA,SPAIN. GEORGETOWN UNIV,HOSP CTR,DEPT OTOLARYNGOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,HOSP CTR,DEPT PEDIAT,WASHINGTON,DC 20007. WASHINGTON HOSP CTR,DEPT FACIAL & RECONSTRUCT SURG,WASHINGTON,DC 20010. NR 30 TC 30 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1992 VL 73 IS 5 BP 2069 EP 2073 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA JZ596 UT WOS:A1992JZ59600053 PM 1474087 ER PT J AU HAUSER, J LEVINE, AS ENNIS, DG CHUMAKOV, KM WOODGATE, R AF HAUSER, J LEVINE, AS ENNIS, DG CHUMAKOV, KM WOODGATE, R TI THE ENHANCED MUTAGENIC POTENTIAL OF THE MUCAB PROTEINS CORRELATES WITH THE HIGHLY EFFICIENT PROCESSING OF THE MUCA PROTEIN SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ULTRAVIOLET-LIGHT MUTAGENESIS; ESCHERICHIA-COLI K-12; RECA PROTEIN; SALMONELLA-TYPHIMURIUM; DNA-REPAIR; SOS MUTAGENESIS; UV-MUTAGENESIS; HEMOPHILUS-INFLUENZAE; REPRESSOR CLEAVAGE; DEPENDENT CLEAVAGE AB Inducible mutagenesis in Escherichia coli requires the direct action of the chromosomally encoded UmuDC proteins or functional homologs found on certain naturally occurring plasmids. Although structurally similar, the five umu-like operons that have been characterized at the molecular level vary in their ability to enhance cellular and phage mutagenesis; of these operons, the mucAB genes from the N-group plasmid pKM101 are the most efficient at promoting mutagenesis. During the mutagenic process, UmuD is posttranslationally processed to an active form, UmuD'. To explain the more potent mutagenic efficiency of mucAB compared with that of umuDC it has been suggested that unlike UmuD, intact MucA is functional for mutagenesis. To examine this possibility, we have overproduced and purified the MucA protein. Although functionally similar to UmuD, MucA was cleaved much more rapidly both in vitro and in vivo than UmuD. In vivo, restoration of mutagenesis functions to normally nonmutable recA430, recA433, recA435, or recA730 DELTA(umuDC)595::cat strains by either MucA+ or mutant MucA protein correlated with the appearance of the cleavage product, MucA'. These results suggest that most of the differences in mutagenic phenotype exhibited by MucAB and UmuDC correlate with the efficiency of posttranslational processing of MucA and UmuD rather than an inherent activity of the unprocessed proteins. C1 NICHHD,VIRUSES & CELLULAR BIOL SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT RES,BETHESDA,MD 20892. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 62 TC 47 Z9 47 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 NOV PY 1992 VL 174 IS 21 BP 6844 EP 6851 PG 8 WC Microbiology SC Microbiology GA JW091 UT WOS:A1992JW09100016 PM 1400235 ER PT J AU GEBER, A WILLIAMSON, PR REX, JH SWEENEY, EC BENNETT, JE AF GEBER, A WILLIAMSON, PR REX, JH SWEENEY, EC BENNETT, JE TI CLONING AND CHARACTERIZATION OF A CANDIDA-ALBICANS MALTASE GENE INVOLVED IN SUCROSE UTILIZATION SO JOURNAL OF BACTERIOLOGY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; ALPHA-GLUCOSIDASE GENE; SCHWANNIOMYCES-CASTELLII; MAL6 LOCUS; SEQUENCE; STELLATOIDEA; EXPRESSION; IDENTIFICATION; CARLSBERGENSIS; GLUCOAMYLASE AB In order to isolate the structural gene involved in sucrose utilization, we screened a sucrose-induced Candida albicans cDNA library for clones expressing alpha-glucosidase activity. The C. albicans maltase structural gene (CAMAL2) was isolated. No other clones expressing alpha-glucosidase activity were detected. A genomic CAMAL2 clone was obtained by screening a size-selected genomic library with the cDNA clone. DNA sequence analysis reveals that CAMAL2 encodes a 570-amino-acid protein which shares 50% identity with the maltase structural gene (MAL62) of Saccharomyces carlsbergensis. The substrate specificity of the recombinant protein purified from Escherichia coli identifies the enzyme as a maltase. Northern (RNA) analysis reveals that transcription of CAMAL2 is induced by maltose and sucrose and repressed by glucose. These results suggest that assimilation of sucrose in C. albicans relies on an inducible maltase enzyme. The family of genes controlling sucrose utilization in C. albicans shares similarities with the MAL gene family of Saccharomyces cerevisiae and provides a model system for studying gene regulation in this pathogenic yeast. RP GEBER, A (reprint author), NIAID,CLIN INVEST LAB,BETHESDA,MD 20892, USA. NR 39 TC 58 Z9 61 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 NOV PY 1992 VL 174 IS 21 BP 6992 EP 6996 PG 5 WC Microbiology SC Microbiology GA JW091 UT WOS:A1992JW09100034 PM 1400249 ER PT J AU GARCIA, GE STADTMAN, TC AF GARCIA, GE STADTMAN, TC TI CLOSTRIDIUM-STICKLANDII GLYCINE REDUCTASE SELENOPROTEIN-A GENE - CLONING, SEQUENCING, AND EXPRESSION IN ESCHERICHIA-COLI SO JOURNAL OF BACTERIOLOGY LA English DT Article ID INDUCIBLE FORMATE DEHYDROGENASE; NUCLEOTIDE-SEQUENCE; SELENIUM METABOLISM; PROTEIN-COMPONENTS; MESSENGER-RNA; OPAL UGA; SELENOCYSTEINE; PURIFICATION; COMPLEX; IDENTIFICATION AB Gene grdA, which encodes selenoprotein A of the glycine reductase complex from Clostridium sticklandii, was identified and characterized. This gene encodes a protein of 158 amino acids with a calculated M(r) of 17,142. The known sequence of 15 amino acids around the selenocysteine residue and the known carboxy terminus of the protein are correctly predicted by the nucleotide sequence. An opal termination codon (TGA) corresponding to the location of the single selenocysteine residue in the polypeptide was found in frame at position 130. The C. sticklandii grdA gene was inserted behind the tac promotor of an Escherichia coli expression vector. An E. coli strain transformed with this vector produced an 18-kDa polypeptide that was not detected in extracts of nontransformed cells. Affinity-purified anti-C. sticklandii selenoprotein A immunoglobulin G reacted specifically with this polypeptide, which was indistinguishable from authentic C. sticklandii selenoprotein A by immunological analysis. Addition of the purified expressed protein to glycine reductase protein components B and C reconstituted the active glycine reductase complex. Although synthesis of enzymically active protein A depended on the presence of selenium in the growth medium, formation of immunologically reactive protein did not. Moreover, synthesis of enzymically active protein in a transformed E. coli selD mutant strain indicated that there is a nonspecific mechanism of selenocysteine incorporation. These findings imply that mRNA secondary structures of C. sticklandii grdA are not functional for UGA-directed selenocysteine insertion in the E. coli expression system. C1 NHLBI,BIOCHEM LAB,BLDG 3,ROOM 108,BETHESDA,MD 20892. NR 37 TC 22 Z9 24 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 NOV PY 1992 VL 174 IS 22 BP 7080 EP 7089 PG 10 WC Microbiology SC Microbiology GA JY560 UT WOS:A1992JY56000003 PM 1429431 ER PT J AU MANCHCITRON, JN ALLEN, J MOOS, M LONDON, J AF MANCHCITRON, JN ALLEN, J MOOS, M LONDON, J TI THE GENE ENCODING A PREVOTELLA-LOESCHEII LECTIN-LIKE ADHESIN CONTAINS AN INTERRUPTED SEQUENCE WHICH CAUSES A FRAMESHIFT SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ORAL BACTERIA; DNA; COAGGREGATIONS; HYBRIDIZATION; PURIFICATION; CLONING; VECTORS AB We cloned and sequenced the Prevotella loescheii gene plaA, which encodes a lectin-like adhesin that mediates the coaggregation of P. loescheii 1295 with Streptococcus oralis 34. A probe derived from the N-terminal amino acid sequence of the purified adhesin was used to identify the plaA gene from a P. loescheii genomic library constructed in lambda GEM-11. Sequence analysis of plaA indicates that the initial translation product contains a 22-amino-acid leader. The reading frame of the plaA gene is interrupted after amino acid 28 of the mature protein by a TAA termination codon. Amplification of the P. loescheii genomic DNA in the region surrounding this codon by the polymerase chain reaction followed by DNA sequencing of the cloned DNA fragment established that this stop codon was not an experimental artifact. A frameshift beginning 29 bp downstream of the ochre terminator was required to access the only large open reading frame in the gene. Amino acid sequences of six purified peptides derived by limited proteolysis of adhesin with endoproteinase Lys-C matched the downstream amino acid sequence derived by translation of the large open reading frame. The gene coding sequence of 2.4 kb contains sufficient information for the synthesis of an 89-kDa protein. A putative rho-independent terminator (DELTAG = -25.5 kcal/mol [ca. -107 kJ/mol]) was detected 38 bp downstream from the plaA stop codon. C1 US FDA,CTR BIOL EVALUAT & RES,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP MANCHCITRON, JN (reprint author), NATL INST DENTAL RES,MICROBIAL ECOL LAB,BETHESDA,MD 20892, USA. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 FU NIDCR NIH HHS [5F32DEO5554] NR 27 TC 16 Z9 17 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 NOV PY 1992 VL 174 IS 22 BP 7328 EP 7336 PG 9 WC Microbiology SC Microbiology GA JY560 UT WOS:A1992JY56000035 PM 1429455 ER PT J AU JUHNN, YS JONES, TLZ SPIEGEL, AM AF JUHNN, YS JONES, TLZ SPIEGEL, AM TI AMINO-TERMINAL AND CARBOXY-TERMINAL DELETION MUTANTS OF GS-ALPHA ARE LOCALIZED TO THE PARTICULATE FRACTION OF TRANSFECTED COS CELLS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GAMMA SUBUNITS CONTAIN; BETA-GAMMA; PLASMA-MEMBRANE; GTP-BINDING; BOVINE BRAIN; PROTEIN; ASSOCIATION; EXPRESSION; ANTIBODIES; TRANSDUCIN AB To elucidate the structural basis for membrane attachment of the alpha subunit of the stimulatory G protein (Gsalpha), mutant Gsalpha cDNAs with deletions of amino acid residues in the amino and/or carboxy termini were transiently expressed in COS-7 cells. The particulate and soluble fractions prepared from these cells were analyzed by immunoblot using peptide specific antibodies to monitor distribution of the expressed proteins. Transfection of mutant forms of Gsalpha with either 26 amino terminal residues deleted (DELTA3-28) or with 59 amino terminal residues deleted (DELTA1-59) resulted in immunoreactive proteins which localized primarily to the particulate fraction. Similarly, mutants with 10 (DELTA385-394), 32 (DELTA353-384), or 42 (DELTA353-394) amino acid residues deleted from the carboxy terminus also localized to the particulate fraction, as did a mutant form of Gsalpha lacking amino acid residues at both the amino and carboxy termini (DELTA3-28)/(DELTA353-384). Mutant and wild type forms of Gsalpha demonstrated a similar degree of tightness in their binding to membranes as demonstrated by treatment with 2.5 M NaCl or 6 M urea, but some mutant forms were relatively resistant compared with wild type Gsalpha to solubilization by 15 mM NaOH or 1% sodium cholate. We conclude that: (a) deletion of significant portions of the amino and/or carboxyl terminus of Gsalpha is still compatible with protein expression; (b) deletion of these regions is insufficient to cause cytosolic localization of the expressed protein. The basis of Gsalpha membrane targeting remains to be elucidated. C1 NIDDKD, MOLEC PATHOPHYSIOL BRANCH, BETHESDA, MD 20892 USA. RI Juhnn, Yong-Sung/J-2790-2012 NR 39 TC 21 Z9 21 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD NOV PY 1992 VL 119 IS 3 BP 523 EP 530 DI 10.1083/jcb.119.3.523 PG 8 WC Cell Biology SC Cell Biology GA JV269 UT WOS:A1992JV26900004 PM 1400589 ER PT J AU KIM, LT ISHIHARA, S LEE, CC AKIYAMA, SK YAMADA, KM GRINNELL, F AF KIM, LT ISHIHARA, S LEE, CC AKIYAMA, SK YAMADA, KM GRINNELL, F TI ALTERED GLYCOSYLATION AND CELL-SURFACE EXPRESSION OF BETA-1 INTEGRIN RECEPTORS DURING KERATINOCYTE ACTIVATION SO JOURNAL OF CELL SCIENCE LA English DT Article DE KERATINOCYTES; INTEGRINS; WOUND REPAIR ID HUMAN FIBRONECTIN RECEPTOR; GROWTH FACTOR-BETA; BULLOUS PEMPHIGOID ANTIGEN; ADHESION RECEPTORS; TERMINAL DIFFERENTIATION; EPIDERMAL-CELLS; VLA PROTEINS; MATRIX; FAMILY; SUBUNIT AB We studied the mechanism by which cell adhesiveness becomes activated when keratinocytes are removed from skin and placed into cell culture. Our results suggest that activation involves altered beta1 integrin subunit glycosylation accompanied by an increase in cell surface beta1 integrin receptors. Activated keratinocytes contained two forms of the beta1 integrin subunit, approximately 93 kDa and approximately 113 kDa. As shown by pulse-chase experiments, the smaller represented the cytoplasmic precursor of the larger, and only the 113 kDa mature form was detected in integrin receptors expressed at the cell surface. Preactivated keratinocytes contained beta1 integrin subunits ranging from approximately 97 to 110 kDa. These beta1 subunits had been processed through the Golgi, based on resistance to endoglycosidase-H treatment, and were not converted to 113 kDa subunits during subsequent cell culture. Experiments with endoglycosidase-F showed that differences in the apparent sizes of beta1 integrin subunits observed in pre-activated and activated keratinocytes could be attributed to differences in subunit glycosylation. Smaller beta1 subunits found in pre-activated keratinocytes, like the precursor beta1 subunits of activated cells, appeared to be less efficient in reaching the cell surface. Overall, a approximately 10-fold increase in the level of cell surface integrin receptors occurred concomitant with the increased proportion of 113 kDa beta1 subunits found in activated cells. Endoglycosidase-F experiments also indicated that there were changes in keratinocyte alpha subunits associated with beta1. In related experiments, keratinocytes cultured in low Ca2+, serum-free MCDB medium for 4 days proliferated but their adhesiveness did not become activated. Therefore, keratinocyte proliferation and activation of adhesion are regulated separately. Finally, substantial activation of keratinocytes was observed when serum was added to cells cultured in MCDB with serum, indicating a role for serum factors in the activation process. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. UT,SW MED CTR,DEPT CELL BIOL & NEUROSCI,DALLAS,TX 75235. FU NIAID NIH HHS [AI17363]; NIGMS NIH HHS [GM31321] NR 52 TC 39 Z9 39 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV PY 1992 VL 103 BP 743 EP 753 PN 3 PG 11 WC Cell Biology SC Cell Biology GA KC006 UT WOS:A1992KC00600014 PM 1336016 ER PT J AU KORNYSHEV, AA KOSSAKOWSKI, DA LEIKIN, S AF KORNYSHEV, AA KOSSAKOWSKI, DA LEIKIN, S TI SURFACE PHASE-TRANSITIONS AND HYDRATION FORCES SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MEMBRANES; BILAYERS; WATER AB The interplay between surface phase transitions and hydration forces (considered to be important in multilamellar lipid systems, DNA assemblies, and proteins) is studied using a mean-field Landau theory with two coupled order parameters. The latter represent water ordering at two surfaces separated by a thin water film. A complete analytical solution gives a phase diagram in the temperature/surface-separation plane, phase trajectories, and force-distance curves. The phase diagram shows nontrivial effects on surface phase transitions from hydration interaction between the surfaces. For example, these are second- and first-order transitions at finite separation, which are absent at isolated surfaces (infinite separation). The force-distance diagram displays correspondingly drastic effects of the phase transitions on hydration forces. This is a spike in the force at the second-order transition and a jump crossover from repulsion to attraction at the first-order transition. C1 NIH, DIV COMP RES & TECHNOL,PHYS SCI LAB,BLDG 12A, RM 2007, BETHESDA, MD 20892 USA. TECH UNIV MUNICH, MED BIOPHYS LAB, CLIN RDI, W-8000 MUNICH 80, GERMANY. AN FRUMKIN ELECTROCHEM INST, MOSCOW 117071, USSR. FORSCHUNGSZENTRUM JULICH, IEV, W-5170 JULICH 1, GERMANY. MOSCOW PHYS TECH INST, FAC PHYSICOCHEM BIOL, MOSCOW 141700, USSR. JOINT NUCL RES INST, THEORET PHYS, DUBNA 141980, USSR. RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 29 TC 18 Z9 18 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 1 PY 1992 VL 97 IS 9 BP 6809 EP 6820 DI 10.1063/1.463634 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA JX295 UT WOS:A1992JX29500093 ER PT J AU AVGERINOS, PC KIAMOURIS, CK PETRAKOS, IP KLEANTHOUS, IK ZORZOS, PA DIMITRIADIS, TN RAPTIS, SA CUTLER, GB AF AVGERINOS, PC KIAMOURIS, CK PETRAKOS, IP KLEANTHOUS, IK ZORZOS, PA DIMITRIADIS, TN RAPTIS, SA CUTLER, GB TI PULSATILE HUMAN CORTICOTROPIN-RELEASING HORMONE PREVENTS DEXAMETHASONE-INDUCED SUPPRESSION OF THE PLASMA-CORTISOL RESPONSE TO HYPOGLYCEMIA IN NORMAL MEN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-INDUCED HYPOGLYCEMIA; ARGININE VASOPRESSIN; CUSHINGS-DISEASE; ACTH-SECRETION; ADRENOCORTICOTROPIN; DEPRESSION; AVP AB Insulin-induced hypoglycemia causes a sequential stimulation of all three components of the hypothalamic-pituitary-adrenal axis. States of acute glucocorticoid excess, such as the overnight (1 mg) dexamethasone suppression test (DST), inhibit both the basal cortisol level and the response to an insulin tolerance test (ITT). However, whether this negative feedback effect is exerted primarily at the hypothalamic or the pituitary level is not clear. To explore this question further we have examined the cortisol response to insulin-induced hypoglycemia in three experimental settings, in the following order: 1) a control ITT performed at 0900 h after an overnight hospital stay (cITT); 2) an ITT at 0900 h after oral dexamethasone, 1 mg, at 2300 h on the previous evening (DST + ITT); and 3) an ITT at 0900 h after dexamethasone, 1 mg, at 2300 h and hCRH, 1 mug/kg iv, at 90 min intervals from 0100-0700 h (DST + hCRH + ITT). The response to ITT was defined as the peak cortisol increment (peak minus baseline). Since the study objective was to test whether overnight pulsatile hCRH could prevent dexamethasone-induced suppression of the response to a morning ITT, only subjects that demonstrated a greater than 25% decrease in the cortisol response to DST + ITT vs. cITT received the full protocol (five of nine normal men). Basal ACTH and cortisol secretion remained suppressed throughout the night during both the Dex + ITT and Dex + hCRH + ITT studies when compared to the control study (cITT, P < 0.05). However, the cortisol response to hypoglycemia during DST + hCRH + ITT was significantly greater than during DST + ITT (P < 0.05) and was similar to the cITT response. Thus, pulsatile hCRH, administered during the 10 h between dexamethasone and the subsequent hypoglycemic stimulus, prevented acute suppression by dexamethasone of the cortisol response to hypoglycemia. We conclude that the dexamethasone-induced inhibition of the cortisol response to hypoglycemia results primarily from suppression by dexamethasone of basal hypothalamic corticotropin-releasing factor and the consequent impairment of corticotroph responsiveness to exogenous and endogenous corticotropin-releasing factor. C1 NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. UNIV ATHENS, EVANGELISMOS HOSP, DEPT INTERNAL MED 2, GR-10676 ATHENS, GREECE. NR 25 TC 6 Z9 6 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1992 VL 75 IS 5 BP 1358 EP 1361 DI 10.1210/jc.75.5.1358 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JX176 UT WOS:A1992JX17600032 PM 1331166 ER PT J AU SIEGLER, IC PETERSON, BL BAREFOOT, JC HARVIN, SH DAHLSTROM, WG KAPLAN, BH COSTA, PT WILLIAMS, RB AF SIEGLER, IC PETERSON, BL BAREFOOT, JC HARVIN, SH DAHLSTROM, WG KAPLAN, BH COSTA, PT WILLIAMS, RB TI USING COLLEGE ALUMNI POPULATIONS IN EPIDEMIOLOGIC RESEARCH - THE UNC ALUMNI HEART-STUDY SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE HOSTILITY; METHODS; SELECTION BIAS ID FOLLOW-UP; TOTAL MORTALITY; HOSTILITY; DISEASE AB The UNC Alumni Heart Study (UNCAHS) is a prospective study of the role of psychosocial factors, in particular hostility, in the development of coronary heart disease. The target population is composed of persons who completed the Minnesota Multiphasic Personality Inventory while attending the University of North Carolina in the mid-1960s. Logistic regression analyses were used to determine whether hostility, demographic and other variables were significant determinants of the subjects' locatability and participation. It was found that MMPI hostility scores at initial testing were unrelated to either potential or actual locatability or participation. Thus there is no evidence that hostility is the source of selection bias in the UNCAHS. Selection into the study was predicted by age, sex, degree status and variables concerned with the conditions under which the MMPI was administered. It is concluded that follow-up studies of college cohorts may have study-specific sources of selection bias. C1 DUKE UNIV,BEHAV MED RES CTR,DURHAM,NC 27706. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. UNIV N CAROLINA,DEPT PSYCHOL,CHAPEL HILL,NC 27514. RP SIEGLER, IC (reprint author), DUKE UNIV,MED CTR,DEPT COMMUNITY & FAMILY MED,DURHAM,NC 27710, USA. OI Costa, Paul/0000-0003-4375-1712 FU NHLBI NIH HHS [1 P01 HL36587]; NIMH NIH HHS [K05 MH70482] NR 24 TC 30 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD NOV PY 1992 VL 45 IS 11 BP 1243 EP 1250 DI 10.1016/0895-4356(92)90165-J PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA JX506 UT WOS:A1992JX50600007 PM 1432005 ER PT J AU SMITH, PD SAINI, SS RAFFELD, M MANISCHEWITZ, JF WAHL, SM AF SMITH, PD SAINI, SS RAFFELD, M MANISCHEWITZ, JF WAHL, SM TI CYTOMEGALOVIRUS INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA BY HUMAN MONOCYTES AND MUCOSAL MACROPHAGES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CYTOMEGALOVIRUS; TUMOR NECROSIS FACTOR; AIDS; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD MONOCYTES; PLATELET-ACTIVATING FACTOR; AIDS-RELATED COMPLEX; GENE-EXPRESSION; MONONUCLEAR-CELLS; BOWEL NECROSIS; INTERLEUKIN-1; INFECTION; TYPE-1 AB Cytomegalovirus (CMV) is a major cause of inflammatory organ disease in immunosuppressed persons. To elucidate the mechanisms of CMV-induced inflammation, we investigated whether tumor necrosis factor-alpha (TNF-alpha) was involved in the pathogenesis of CMV colitis in patients with AIDS. In in situ hybridization experiments, TNF-alpha mRNA was shown to be abundantly present in colonic mucosa from AIDS patients with CMV colitis but not in colonic mucosa from control (AIDS and normal) subjects. The TNF-alpha transcripts, identified in macrophage-like cells containing cytomegalic inclusions, were positively associated with CMV, but not HIV-1, within the mucosa. In in vitro experiments, a patient-derived isolate of CMV, but not HIV-1Ba-L, induced human monocytes to express TNF-alpha mRNA and to release increased levels of TNF-alpha peptide following stimulation. CMV induction of TNF-alpha may play a critical role in CMV-induced inflammation and, since TNF-alpha upregulates expression of HIV-1, offers a mechanism by which CMV could serve as a co-factor for HIV-1 expression without both viruses infecting the same cell. C1 US FDA,CTR BIOL & RES,BETHESDA,MD 20892. NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. RP SMITH, PD (reprint author), NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BLDG 30,ROOM 322,BETHESDA,MD 20892, USA. NR 49 TC 122 Z9 123 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 NOV PY 1992 VL 90 IS 5 BP 1642 EP 1648 DI 10.1172/JCI116035 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JZ475 UT WOS:A1992JZ47500002 PM 1331170 ER PT J AU VISWANATHAN, M STROMBERG, C SELTZER, A SAAVEDRA, JM AF VISWANATHAN, M STROMBERG, C SELTZER, A SAAVEDRA, JM TI BALLOON ANGIOPLASTY ENHANCES THE EXPRESSION OF ANGIOTENSIN-II AT1 RECEPTORS IN NEOINTIMA OF RAT AORTA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ANGIOTENSIN-II; ANGIOTENSIN-CONVERTING ENZYME; ANGIOTENSIN RECEPTOR SUBTYPES; GROWTH; VASCULAR SMOOTH MUSCLE ID SMOOTH-MUSCLE CELLS; VASCULAR RENIN-ANGIOTENSIN; HUMAN ATHEROSCLEROTIC PLAQUES; FACTOR MESSENGER-RNA; FACTOR-A-CHAIN; GROWTH-FACTOR; CONVERTING ENZYME; GENE-EXPRESSION; CELLULAR PROLIFERATION; LESION FORMATION AB Angiotensin II is a vasoactive peptide and may act as a growth factor in vascular smooth muscle cells. Experimental injury of the rat aorta causes rapid migration of medial smooth muscle cells and their proliferation resulting in the formation of neointima. We have examined, using quantitative autoradiography, the expression of angiotensin II receptor subtypes AT1 and AT2, and angiotensin-converting enzyme, in the neointima formed in the rat thoracic aorta 15 d after balloon-catheter injury. In contrast to the normal aortic wall, which contained both AT1 and AT2 receptors (80% and 20%, respectively), neointimal cells expressed almost exclusively angiotensin II AT1 receptors. The apparent number of these receptors was fourfold higher in the neointima compared to that in the normal aortic wall. The affinities of the neointimal receptors to angiotensin II or to the AT1 receptor antagonist, losartan, were not different from those in the normal aortic wall. Angiotensin-converting enzyme binding in the neointima was not different from that in the media of the uninjured aorta. Our data suggest that angiotensin II AT1 receptors may have a significant role in injury-induced vascular smooth muscle proliferation and migration. RP VISWANATHAN, M (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 40 TC 131 Z9 132 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 NOV PY 1992 VL 90 IS 5 BP 1707 EP 1712 DI 10.1172/JCI116043 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JZ475 UT WOS:A1992JZ47500010 PM 1331171 ER PT J AU ROBERTS, AB ROCHE, NS WINOKUR, TS BURMESTER, JK SPORN, MB AF ROBERTS, AB ROCHE, NS WINOKUR, TS BURMESTER, JK SPORN, MB TI ROLE OF TRANSFORMING GROWTH-FACTOR-BETA IN MAINTENANCE OF FUNCTION OF CULTURED NEONATAL CARDIAC MYOCYTES - AUTOCRINE ACTION AND REVERSAL OF DAMAGING EFFECTS OF INTERLEUKIN-1 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE TRANSFORMING GROWTH FACTOR-BETA; INTERLEUKIN-1; HEART; MYOCARDIUM; EXTRACELLULAR MATRIX ID CELL-ADHESION RECEPTORS; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; FIBROBLAST GROWTH; GENE-EXPRESSION; TGF-BETA; INHIBITION; PROTEIN; FACTOR-BETA-1; PROTEOGLYCAN AB The three isoforms of transforming growth factor-beta (TGF-beta) have previously been implicated in embryonic development of the heart as well as in repair of myocardial damage after ischemia/reperfusion injury. TGF-beta1 has also been localized intracellularly to both mitochondria and contractile filaments of cardiac myocytes, although its role in these structures has not been defined. We now report that exogenous TGF-beta stabilizes the beating rate of neonatal rat cardiac myocytes cultured on fibroblast matrix, and sustains their spontaneous rhythmic beating in serum-free medium. Moreover, using blocking antibodies to TGF-beta, we show that endogenous TGF-beta secreted by these myocytes acts in an autocrine fashion to maintain their beating rate. In contrast, IL-1beta, an inflammatory mediator secreted by immune cells during myocardial injury, inhibits the beating of cardiac myoCytes, and TGF-beta can overcome this inhibition. The antagonistic effects of TGF-beta and IL-1 were not observed when the myocytes were cultured on gelatin, as compared to native fibroblast matrix. The data indicate that TGF-beta is an important regulator of contractile function of the heart and have significant implications for understanding cardiac physiology in health and disease. RP ROBERTS, AB (reprint author), NCI,CHEMOPREVENT LAB,BLDG 41,ROOM C-629,BETHESDA,MD 20892, USA. NR 45 TC 100 Z9 102 U1 0 U2 3 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 NOV PY 1992 VL 90 IS 5 BP 2056 EP 2062 DI 10.1172/JCI116087 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JZ475 UT WOS:A1992JZ47500054 PM 1430228 ER PT J AU SANFORD, KK PARSHAD, R PRICE, FM TARONE, RE KRAEMER, KH AF SANFORD, KK PARSHAD, R PRICE, FM TARONE, RE KRAEMER, KH TI RETINOID PROTECTION AGAINST X-RAY-INDUCED CHROMATID DAMAGE IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE XERODERMA-PIGMENTOSUM; ISOTRETINOIN; OXIDATIVE DNA DAMAGE; SKIN CANCER; CYTOGENETICS ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; PROSTAGLANDIN-H SYNTHASE; DEFICIENT DNA-REPAIR; PROTEIN KINASE-C; XERODERMA PIGMENTOSUM; 13-CIS-RETINOIC ACID; VITAMIN-A; G2 PHASE; LIPID-PEROXIDATION; FLUORESCENT LIGHT AB Oral administration of isotretinoin (13-cis retinoic acid) was shown previously (Kraemer, K. H., J. J. DiGiovanna, A. N. Moshell, R. E. Tarone, and G. L. Peck. 1988. N. Engl. J. Med. 318:1633-1637) to reduce the frequency of skin cancers in xeroderma pigmentosum (XP) patients. The mechanism of protection was unclear. In the present study, x-ray-induced chromatid damage in PHA-stimulated blood lymphocytes from five XP patients receiving isotretinoin was approximately half that in blood samples from the same patients before or subsequent to treatment. The x-ray-induced chromatid damage in blood lymphocytes from a normal control was reduced significantly by cocultivation with blood or plasma from an XP patient receiving isotretinoin or by addition of 10(-6) M isotretinoin to cultures 1 h before x-irradiation. A similar reduction in x-ray-induced chromatid damage was reported previously by adding to the culture medium, mannitol, a scavenger of the free hydroxyl radical, or catalase, which decomposes hydrogen peroxide; both of these products are generated during ionizing radiation. The present observations suggest that isotretinoin acts as a scavenger of such radiation products, thereby providing protection against x-ray-induced chromatid damage. C1 HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20059. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP SANFORD, KK (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 2D15,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 62 TC 13 Z9 13 U1 0 U2 1 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 NOV PY 1992 VL 90 IS 5 BP 2069 EP 2074 DI 10.1172/JCI116089 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JZ475 UT WOS:A1992JZ47500056 PM 1430230 ER PT J AU MARCONI, RT GARON, CF AF MARCONI, RT GARON, CF TI DEVELOPMENT OF POLYMERASE CHAIN-REACTION PRIMER SETS FOR DIAGNOSIS OF LYME-DISEASE AND FOR SPECIES-SPECIFIC IDENTIFICATION OF LYME-DISEASE ISOLATES BY 16S RIBOSOMAL-RNA SIGNATURE NUCLEOTIDE ANALYSIS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BORRELIA-BURGDORFERI DNA; ACRODERMATITIS CHRONICA ATROPHICANS AB We have determined and compared partial 16S rRNA sequences from 23 Lyme disease spirochete isolates and aligned these with 8 sequences previously presented. The 16S rRNA signature nucleotide compositions were defined for each isolate and compared with the genomic species signature nucleotide sets previously established. To identify positions truly indicative of species classification which could serve as targets for polymerase chain reaction species-specific identification primers, 16S rRNA-based phylogenetic analyses were conducted. On the basis of the identified signature nucleotides, we designed polymerase chain reaction primer sets which (i) amplify all spirochete species associated with Lyme disease and (ii) differentiate between these species. The primer sets were tested on 38 Borrelia isolates associated with Lyme disease and were found to be sensitive and specific. All Lyme disease isolates tested were amplification positive. These primers allow for the rapid species identification of Lyme disease isolates. RP MARCONI, RT (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 28 TC 165 Z9 174 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 NOV PY 1992 VL 30 IS 11 BP 2830 EP 2834 PG 5 WC Microbiology SC Microbiology GA JU856 UT WOS:A1992JU85600016 PM 1280643 ER PT J AU VARMA, A KWONCHUNG, KJ AF VARMA, A KWONCHUNG, KJ TI DNA PROBE FOR STRAIN TYPING OF CRYPTOCOCCUS-NEOFORMANS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; GEL-ELECTROPHORESIS AB A 7-kb linear plasmid, harbored by a URA5 transformant, hybridized to all the chromosomes of Cryptococcus neoformans separated by contour-clamped homogeneous electric field electrophoresis. Its linear maintenance was determined to have been facilitated by the presence of telomere-like sequences at its free ends. Hybridization of this plasmid to AccI-digested genomic DNAs of 26 C neoformans strains generated 21 unique DNA fingerprints. The DNA fingerprints of isolates within the same serotype were more similar to one another than to those from different serotypes. An acapsular clinical isolate, strain 602, widely used in immunological studies and previously thought to be in serotype D, showed DNA fingerprints typical of serotype A isolates. Isogenic strains of C. neoformans exhibited DNA fingerprints that were identical to one another. The DNA fingerprints were stable and reproducible in spite of repeated transfers in the laboratory on either complex (1% yeast extract, 2% Bacto Peptone, 2% glucose) or minimal (yeast nitrogen base) medium. The DNA fingerprints of isolates recovered from primary blood and cerebrospinal fluid cultures of patients for whom AIDS had been diagnosed showed that the original infection in each of these patients contained a homogeneous population of C. neoformans. The DNA fingerprints of isolates recovered from different tissues of infected mice and from patients undergoing different drug therapy regimens were also found to be very stable. RP VARMA, A (reprint author), NIAID, CLIN INVEST LAB, CLIN MYCOL SECT, BETHESDA, MD 20892 USA. NR 25 TC 61 Z9 61 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1992 VL 30 IS 11 BP 2960 EP 2967 PG 8 WC Microbiology SC Microbiology GA JU856 UT WOS:A1992JU85600039 PM 1452666 ER PT J AU SMITH, MA ADAMSON, PC BALIS, FM FEUSNER, J ARONSON, L MURPHY, RF HOROWITZ, ME REAMAN, G HAMMOND, GD FENTON, RM CONNAGHAN, GD HITTELMAN, WN POPLACK, DG AF SMITH, MA ADAMSON, PC BALIS, FM FEUSNER, J ARONSON, L MURPHY, RF HOROWITZ, ME REAMAN, G HAMMOND, GD FENTON, RM CONNAGHAN, GD HITTELMAN, WN POPLACK, DG TI PHASE-I AND PHARMACOKINETIC EVALUATION OF ALL-TRANS-RETINOIC ACID IN PEDIATRIC-PATIENTS WITH CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; PREMATURE CHROMOSOME CONDENSATION; CELL-LINES; DIFFERENTIATION THERAPY; CYTOGENETIC ANALYSIS; INDUCTION; INVITRO; INVIVO; GROWTH; ISOTRETINOIN C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. CHILDRENS CANC STUDY GRP,ARCADIA,CA. NR 59 TC 128 Z9 129 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1992 VL 10 IS 11 BP 1666 EP 1673 PG 8 WC Oncology SC Oncology GA JV900 UT WOS:A1992JV90000003 PM 1403049 ER PT J AU WILSON, WH JAIN, V BRYANT, G COWAN, KH CARTER, C COTTLERFOX, M GOLDSPIEL, B STEINBERG, SM LONGO, DL WITTES, RE AF WILSON, WH JAIN, V BRYANT, G COWAN, KH CARTER, C COTTLERFOX, M GOLDSPIEL, B STEINBERG, SM LONGO, DL WITTES, RE TI PHASE-I AND PHASE-II STUDY OF HIGH-DOSE IFOSFAMIDE, CARBOPLATIN, AND ETOPOSIDE WITH AUTOLOGOUS BONE-MARROW RESCUE IN LYMPHOMAS AND SOLID TUMORS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; COMBINATION ALKYLATING-AGENTS; CLINICAL-TRIAL; ADULT PATIENTS; CYTO-TOXICITY; BREAST-CANCER; TRANSPLANTATION; CHEMOTHERAPY; SUPPORT; CYCLOPHOSPHAMIDE C1 NCI,MED BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DIV TRANSFUS MED,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. RP WILSON, WH (reprint author), NCI,DIV CANC TREATMENT,OFF DIRECTOR,BLDG 31,ROOM 3A44,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 79 Z9 80 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 NOV PY 1992 VL 10 IS 11 BP 1712 EP 1722 PG 11 WC Oncology SC Oncology GA JV900 UT WOS:A1992JV90000008 PM 1403054 ER PT J AU ROTHENBERG, M OZOLS, RF YOUNG, RC GLATSTEIN, E STEINBERG, SM REED, E AF ROTHENBERG, M OZOLS, RF YOUNG, RC GLATSTEIN, E STEINBERG, SM REED, E TI CYCLOPHOSPHAMIDE, CISPLATIN, AND ABDOMINAL RADIATION IN ADVANCED OVARIAN-CANCER - REPLY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. UNIV TEXAS,SW MED CTR,DALLAS,TX 75230. NCI,BETHESDA,MD 20892. RP ROTHENBERG, M (reprint author), UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284, USA. NR 3 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1992 VL 10 IS 11 BP 1820 EP 1821 PG 2 WC Oncology SC Oncology GA JV900 UT WOS:A1992JV90000029 ER PT J AU PATRONAS, NJ ARGYROPOULOU, M AF PATRONAS, NJ ARGYROPOULOU, M TI INTRAVASCULAR THROMBOSIS AS A POSSIBLE CAUSE OF TRANSIENT CORTICAL BRAIN-LESIONS - CT AND MRI SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE BRAIN, NEOPLASMS; SEIZURE; MAGNETIC RESONANCE IMAGING; COMPUTED TOMOGRAPHY ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; L-ASPARAGINASE THERAPY; LUPUS ANTICOAGULANT; PLASMA COAGULATION; PLATELET-FUNCTION; CHILDREN; NEUROTOXICITY; CHEMOTHERAPY; CYCLOSPORINE AB Cortical brain lesions were identified on MRI and CT in 14 patients with a variety of diseases. Each of these patients developed neurologic symptoms, the most prominent of which were seizures, depressed mental status, and blurred vision or cortical blindness. Both the imaging and the neurologic abnormalities resolved spontaneously within a period ranging from 5 to 30 days. Due to location and evolution of the lesions over time we hypothesize that they are secondary to small cortical venous thromboses. C1 GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. RP PATRONAS, NJ (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,ROOM 1C660,BETHESDA,MD 20892, USA. NR 26 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 1992 VL 16 IS 6 BP 849 EP 855 DI 10.1097/00004728-199211000-00003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JY187 UT WOS:A1992JY18700003 PM 1430429 ER PT J AU APLAN, PD RAIMONDI, SC KIRSCH, IR AF APLAN, PD RAIMONDI, SC KIRSCH, IR TI DISRUPTION OF THE SCL GENE BY A T(1,3) TRANSLOCATION IN A PATIENT WITH T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SITE-SPECIFIC RECOMBINATION; LOOP-HELIX PROTEIN; CHROMOSOMAL TRANSLOCATIONS; LYMPHOID TUMORS; DNA-BINDING; TAL-1 GENE; SEQUENCES; FRAGMENTS; ENCODES; REGION AB SCL gene disruptions are the most common chromosomal abnormality associated with the development of T cell acute lymphoblastic leukemia (ALL). Such disruptions can be the result of t(1;14) and t(1;7) translocations, as well as a cytogenetically undetectable interstitial deletion of chromosome 1. We present here a case of T cell ALL with a t(1;3)(p34;p21) translocation that also disrupts the SCL locus and leads to dysregulated SCL gene expression. This translocation, similar to previously reported SCL gene disruptions, appears to have been mediated, at least in part, by the V(D)J recombinase complex, since cryptic heptamer recognition sequences, as well as nontemplated N region nucleotide addition, are present at the breakpoints. The t(1;3) also disrupts a region on chromosome 3 characterized by alternating purine and pyrimidine residues, which can form a Z-DNA structure, reported to be prone to recombination events. A previously undescribed, evolutionarily conserved transcript unit is detected within 8 kb of the breakpoint on chromosome 3. This report extends the spectrum of recognized SCL translocations associated with T cell ALL, and underscores the contention that dysregulated SCL expression may be a causal event in T cell ALL. C1 NCI, NAVY MED BRANCH, BETHESDA, MD 20889 USA. NCI, PEDIAT ONCOL BRANCH, BETHESDA, MD 20889 USA. ST JUDE CHILDRENS RES HOSP, DEPT PATHOL LAB MED, MEMPHIS, TN 38105 USA. RI Aplan, Peter/K-9064-2016 FU NCI NIH HHS [CA-20180, CA-21765] NR 30 TC 52 Z9 53 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1992 VL 176 IS 5 BP 1303 EP 1310 DI 10.1084/jem.176.5.1303 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JV012 UT WOS:A1992JV01200008 PM 1402676 ER PT J AU RAWLINGS, DJ KASLOW, DC AF RAWLINGS, DJ KASLOW, DC TI ADJUVANT-DEPENDENT IMMUNE-RESPONSE TO MALARIAL TRANSMISSION-BLOCKING VACCINE CANDIDATE ANTIGENS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID MONOPHOSPHORYL LIPID-A; T-CELL EPITOPES; MEROZOITE SURFACE PROTEIN; PLASMODIUM-FALCIPARUM; CIRCUMSPOROZOITE PROTEIN; ANTIBODY-RESPONSE; TREHALOSE DIMYCOLATE; WALL SKELETON; SEXUAL STAGES; SPOROZOITE AB Immune responses in major histocompatibility complex (MHC)-disparate congenic mouse strains immunized with sexual stage malaria parasites or purified recombinant protein were adjuvant dependent. Whereas mice exhibited a limited antibody response to immunization with newly emerged Plasmodium falciparum gametes in Freund's adjuvant, all five congenic mouse strains responded to several transmission-blocking vaccine candidate antigens, when parasites were emulsified in a monophosphoryl lipid A (MPL) and trehalose dimycolate (TDM) adjuvant. The humoral response in those animals immunized with the antigen in a MPL/TDM adjuvant was helper T cell dependent, as evident by boosting of the antibody response after a second immunization. If the immunogen consisted of purified recombinant protein, then the immune response was not MHC class II limited in mice immunized with either complete Freund's adjuvant or TDM/MPL. The potential role of adjuvants in overcoming apparent immune nonresponsiveness and the implications for development of a malaria transmission-blocking vaccine are discussed. C1 NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,BLDG 4,ROOM B1-37,BETHESDA,MD 20892. NR 34 TC 24 Z9 24 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 NOV 1 PY 1992 VL 176 IS 5 BP 1483 EP 1487 DI 10.1084/jem.176.5.1483 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JV012 UT WOS:A1992JV01200031 PM 1383389 ER PT J AU KIRK, KL NISHIDA, M FUJII, S KIMOTO, H AF KIRK, KL NISHIDA, M FUJII, S KIMOTO, H TI PHOTOCHEMICAL TRIFLUOROMETHYLATION OF TYRAMINE AND L-TYROSINE DERIVATIVES SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article ID IMIDAZOLES; REACTIVITY AB Ultraviolet irradiation (254 nm) of methanolic solutions of trifluoromethyl iodide (CF3I) in the presence of side-chain-protected tyramine and L-tyrosine results in trifluoromethylation of the aromatic ring. The presence of an amine base to neutralize HI formed during the reaction is essential. The electrophilic trifluoromethyl radical preferentially attacks the ring ortho to the phenolic group, and 3-trifluoromethyltyramine and 3-trifluoromethyl-L-tyrosine derivatives were obtained in yields of 27% and 33%, respectively. C1 GOVT IND RES INST,KITA KU,NAGOYA,AICHI 462,JAPAN. RP KIRK, KL (reprint author), NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. RI Nishida, Masakazu/I-7698-2016 OI Nishida, Masakazu/0000-0001-6588-9566 NR 18 TC 6 Z9 6 U1 2 U2 6 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD NOV PY 1992 VL 59 IS 2 BP 197 EP 202 DI 10.1016/S0022-1139(00)82410-0 PG 6 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA KA459 UT WOS:A1992KA45900005 ER PT J AU BERGASA, NV VERGALLA, J COLE, KE WAHL, LM JONES, EA AF BERGASA, NV VERGALLA, J COLE, KE WAHL, LM JONES, EA TI 16,16-DIMETHYL PROSTAGLANDIN-E2 MODULATES AFLATOXIN B1-INDUCED INJURY OF RAT HEPATOCYTES IN PRIMARY CULTURE - POSSIBLE ROLE OF CAMP SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE AFLATOXIN-B1; CYCLIC AMP; CYTOPROTECTION; DMPGE2; HEPATOTOXIN; LIVER INJURY; PGF2-ALPHA; PROSTAGLANDINS; RAT HEPATOCYTES ID HEPATIC-NECROSIS; CELL NECROSIS; CYCLIC-AMP; LIVER; PROTECTION; PGE2; DIFFERENTIATION; INDUCTION; DRUGS AB The hepatocellular cytoprotective effects of 16,16-dimethyl prostaglandin E2 (dmPGE2), ananalogue of PGE2, were investigated using primary cultures of rat hepatocytes and aflatoxin B1 as the hepatotoxin. Lactic dehydrogenase (LDH) release by hepatocytes was used as an index of hepatotoxicity. When aflatoxin-treated hepatocytes were co-cultured with 16,16-dmPGE2 (0.01-0.5 mug/mL) LDH release was significantly reduced and ultrastructural changes of hepatocellular injury were markedly diminished. The magnitude of the cytoprotective effect was not dependent on the concentration of the prostaglandin over the range tested. A significant cytoprotective effect was also induced when hepatocellular cyclic AMP (cAMP) levels were increased by the addition of dibutyl-cAMP. In contrast to 16,16-dmPGE2, PGF2alpha Tromethamine, an analogue of PGF2alpha, which does not stimulate cAMP, induced insignificant changes in cytoprotection. These findings indicate that only a low concentration of 16,16-dmPGE2 (greater-than-or-equal-to 0.01 mug/mL) is necessary to induce a maximal hepatocellular cytoprotective effect and suggest that this effect may be dependent on activation of cAMP. C1 NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. NCI,INVEST DRUG BRANCH,BETHESDA,MD 20892. NATL INST DIABET & DIGEST & KIDNEY DIS,LIVER DIS SECT,DIGEST DIS BRANCH,BETHESDA,MD. NR 36 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD NOV-DEC PY 1992 VL 7 IS 6 BP 608 EP 613 DI 10.1111/j.1440-1746.1992.tb01494.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KG482 UT WOS:A1992KG48200011 PM 1336677 ER PT J AU RIGBY, MA ROJKO, JL STEWART, MA KOCIBA, GJ CHENEY, CM REZANKA, LJ MATHES, LE HARTKE, JR JARRETT, O NEIL, JC AF RIGBY, MA ROJKO, JL STEWART, MA KOCIBA, GJ CHENEY, CM REZANKA, LJ MATHES, LE HARTKE, JR JARRETT, O NEIL, JC TI PARTIAL DISSOCIATION OF SUBGROUP-C PHENOTYPE AND INVIVO BEHAVIOR IN FELINE LEUKEMIA VIRUSES WITH CHIMERIC ENVELOPE GENES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID APLASTIC-ANEMIA RETROVIRUS; INDUCED ERYTHROID APLASIA; RED-CELL APLASIA; LEUKEMIA-VIRUS; MURINE LEUKEMIA; DETERMINANTS; CATS; PATHOGENESIS; SEQUENCE; ASSAY AB Feline leukaemia viruses (FeLVs) are classified into subgroups A, B and C by their use of different host cell receptors on feline cells, a phenotype which is determined by the viral envelope. FeLV-A is the ubiquitous, highly infectious form of FeLV, and FeLV-C isolates are rare variants which are invariably isolated along with FeLV-A. The FeLV-C isolates share the capacity to induce acute non-regenerative anaemia and the prototype, FeLV-C/Sarma, has strongly age-restricted infectivity for cats. The FeLV-C/Sarma env sequence is closely related to that of common, weakly pathogenic FeLV-A isolates. We now show by construction of chimeric viruses that the receptor specificity of FeLV-A/Glasgow-1 virus can be converted to that of FeLV-C by exchange of a single env variable domain, Vr1, which differs by a three codon deletion and nine adjacent substitutions. Attempts to dissect this region further by directed mutagenesis resulted in disabled proviruses. Sequence analysis of independent natural FeLV-C isolates showed that they have unique Vr1 sequences which are distinct from the conserved FeLV-A pattern. The chimeric viruses which acquired the host range and subgroup properties of FeLV-C retained certain FeLV-A-like properties in that they were non-cytopathogenic in 3201B feline T cells and readily induced viraemia in weanling animals. They also induced a profound anaemia in neonates which had a more prolonged course than that induced by FeLV-C/Sarma and which was macrocytic rather than non-regenerative in nature. Although receptor specificity and a major determinant of pathogenicity segregate with Vr1, it appears that sequences elsewhere in the genome influence infectivity and pathogenicity independently of the subgroup phenotype. C1 BEATSON INST CANC RES,CANC RES CAMPAIGN,BEATSON LABS,SWITCHBACK RD,GLASGOW G61 1BD,SCOTLAND. OHIO STATE UNIV,DEPT VET PATHOBIOL,COLUMBUS,OH 43210. NCI,BIOL LAB,BETHESDA,MD 20892. UNIV GLASGOW,DEPT VET PATHOL,GLASGOW G61 1QH,SCOTLAND. FU NCI NIH HHS [CA 40034]; NIAID NIH HHS [AI 25722]; NIDDK NIH HHS [DK 41939]; Wellcome Trust NR 41 TC 55 Z9 55 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 1992 VL 73 BP 2839 EP 2847 DI 10.1099/0022-1317-73-11-2839 PN 11 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA JX105 UT WOS:A1992JX10500009 PM 1331290 ER PT J AU RUBENSTEIN, R DENG, H RACE, RE JU, WN SCALICI, CL PAPINI, MC KASCSAK, RJ CARP, RI AF RUBENSTEIN, R DENG, H RACE, RE JU, WN SCALICI, CL PAPINI, MC KASCSAK, RJ CARP, RI TI DEMONSTRATION OF SCRAPIE STRAIN DIVERSITY IN INFECTED PC12 CELLS SO JOURNAL OF GENERAL VIROLOGY LA English DT Note ID NEURO-BLASTOMA CELLS; MOUSE SCRAPIE; REPLICATION; HAMSTERS; INFECTIVITY; MICE AB Scrapie strain replication in the nerve growth factor-induced, differentiated PC12 cell culture system was examined. Differences in replication between mouse-derived agents were demonstrated, with the 139A scrapie strain yielding 100- to 1000-fold higher levels of infectivity than the ME7 scrapie strain. Replication was not detected in PC12 cells infected with either the hamster-derived 263K or rat-derived 139R scrapie strains. Studies on the neurotransmitters in infected PC12 cells demonstrated that the adrenergic pathway was unchanged but the cholinergic pathway was altered. Furthermore, the degree of alteration correlated with the level of scrapie strain replication. Comparison of infectivity titres and enzymatic changes in ME7-infected PC12 cells with those in Chandler agent-infected mouse neuroblastoma cells suggests that the significant changes in neurotransmitter levels in cultures exhibiting low titres of infectivity involve factors in addition to strain replication. The variation in the range of scrapie strain replication in PC12 cells is discussed in relationship to species barrier, cell targeting, genetic susceptibility and species strain specificity. These studies further emphasize the value of the PC12 cell model system in examining the scrapie strain-host cell interaction and in addition support the concept of variation among scrapie strains. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. RP RUBENSTEIN, R (reprint author), NEW YORK STATE INST BASIC RES DEV DISABILITIES,NEW YORK STATE OFF MENTAL RETARDAT & DEV DISABIL,STATEN ISL,NY 10314, USA. FU NINDS NIH HHS [R29 NS25308] NR 22 TC 24 Z9 26 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD NOV PY 1992 VL 73 BP 3027 EP 3031 DI 10.1099/0022-1317-73-11-3027 PN 11 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA JX105 UT WOS:A1992JX10500034 PM 1359002 ER PT J AU SAAVEDRA, JM CORREA, FMA SELTZER, A PINTO, JEB VIGLIONE, P TSUTSUMI, K AF SAAVEDRA, JM CORREA, FMA SELTZER, A PINTO, JEB VIGLIONE, P TSUTSUMI, K TI ENHANCED ANGIOTENSIN CONVERTING ENZYME BINDING IN ARTERIES FROM SPONTANEOUSLY HYPERTENSIVE RATS SO JOURNAL OF HYPERTENSION LA English DT Article DE VASCULAR ANGIOTENSIN CONVERTING ENZYME; GENETIC HYPERTENSION; QUANTITATIVE AUTORADIOGRAPHY; HEART ANGIOTENSIN CONVERTING ENZYME; RENIN ANGIOTENSIN SYSTEM ID TISSUE ACE ACTIVITY; RENIN-ANGIOTENSIN; KININASE-II; QUANTITATIVE AUTORADIOGRAPHY; BLOOD-PRESSURE; BRAIN; HYPERTROPHY; INHIBITORS; LOCALIZATION; SYSTEM AB Aim: To localize and measure angiotensin converting enzyme (ACE) in different vascular beds of genetically hypertensive rats. Methods: Quantitative autoradiography using the angiotensin converting enzyme (E.C. 3.4.15.1) inhibitor [I-125]351A. Results: [I-125]351A binding was significantly increased in the ascending aorta (both adventitia and intima), descending (abdominal) aorta, carotid artery and coronary arteries of adult, 12-week-old spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats. Increased [I-125]351A binding was also present in the descending aorta of 1-week-old SHR compared with age-matched WKY rats, and both groups of young rats had much higher binding than adult rats. No difference in [I-125]351A binding was found in the caudal (tail) artery of adult SHR compared with WKY rats. In both the atria and the ventricles of adult SHR, [I-125]351A binding was very significantly reduced. Conclusions: Our results indicate that higher ACE concentrations occur in some arteries of genetically hypertensive rats, and support the hypothesis that local arterial concentrations of ACE affect the development and maintenance of genetic hypertension. RP SAAVEDRA, JM (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892, USA. RI Correa, Fernando /D-1614-2012 OI Correa, Fernando /0000-0003-4067-9524 NR 47 TC 19 Z9 20 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD NOV PY 1992 VL 10 IS 11 BP 1353 EP 1359 DI 10.1097/00004872-199211000-00007 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KA289 UT WOS:A1992KA28900007 PM 1336521 ER PT J AU RIBAUDO, RK MARGULIES, DH AF RIBAUDO, RK MARGULIES, DH TI INDEPENDENT AND SYNERGISTIC EFFECTS OF DISULFIDE BOND FORMATION, BETA-2-MICROGLOBULIN, AND PEPTIDES ON CLASS-I MHC FOLDING AND ASSEMBLY IN AN INVITRO TRANSLATION SYSTEM SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; HEAVY-CHAIN; SURFACE EXPRESSION; TRANSPLANTATION ANTIGENS; INTRACELLULAR-TRANSPORT; ENDOPLASMIC-RETICULUM; MICROSOMAL-MEMBRANES; CELL RECOGNITION; DENOVO SYNTHESIS AB We have examined the post-translational processing, intrachain disulfide bond formation, folding, and assembly of MHC class I H chains with beta2-microglobulin after coupled in vitro translation of homogeneous mRNA and transport of nascent chains into canine microsomal vessicles. The formation of native alpha3 domain conformation was dependent on conditions that optimized intrachain disulfide bond formation, and efficient folding of the alpha1alpha2 domain required exposure to antigenic peptide. Beta2-microglobulin and peptide acted synergistically in forming native alpha1alpha2 domain structure, and a small proportion of molecules with native alpha1alpha2, but non-native alpha3 structure were detected, indicating that alpha3 domain folding is not an absolute prerequisite for the formation of native alpha1alpha2 domain structure. RP RIBAUDO, RK (reprint author), NIAID,MOLEC BIOL SECT,IMMUNOL LAB,BLDG 10,ROOM 11N311,BETHESDA,MD 20892, USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 62 TC 68 Z9 68 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 NOV 1 PY 1992 VL 149 IS 9 BP 2935 EP 2944 PG 10 WC Immunology SC Immunology GA JU748 UT WOS:A1992JU74800013 PM 1401922 ER PT J AU ESPINOZADELGADO, I LONGO, DL GUSELLA, GL VARESIO, L AF ESPINOZADELGADO, I LONGO, DL GUSELLA, GL VARESIO, L TI REGULATION OF IL-2 RECEPTOR SUBUNIT GENES IN HUMAN MONOCYTES - DIFFERENTIAL-EFFECTS OF IL-2 AND IFN-GAMMA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERLEUKIN-2 RECEPTOR; PERIPHERAL-BLOOD MONOCYTES; MESSENGER-RNA EXPRESSION; INTERFERON-GAMMA; MICROBICIDAL ACTIVITY; NATURAL-KILLER; CYTO-TOXICITY; P75 SUBUNIT; LYMPHOCYTES; CELLS AB We investigated the effects of IFN-gamma and IL-2 on IL-2R alpha and beta mRNA expression in human monocytes. Low basal expression of IL-2Rbeta mRNA was detected in fresh monocytes. Stimulation of monocytes with IL-2 induced a significant increase of IL-2Rbeta mRNA, but did not induce IL-2Ralpha mRNA. In contrast, stimulation of monocytes with IFN-gamma-induced IL-2Ralpha mRNA, but did not modify IL-2Rbeta mRNA. Five U/ml of IFN-gamma induced IL-2Ralpha mRNA and 2.2 nM of IL-2 induced IL-2Rbeta mRNA, both within 3 h. Nuclear run-on experiments demonstrated that the induction of IL-2Ralpha mRNA by IFN-gamma is controlled, at least in part, at the transcriptional level. In contrast, the enhancement of IL-2Rbeta mRNA by IL-2 is controlled at a posttranscriptional level and is associated with an increase in the half-life of IL-2Rbeta mRNA. The results of studies on the cytotoxic activity and on the expression of c-fms mRNA of monocytes activated by the combination of IFN-gamma and IL-2 show that pretreatment with IFN-gamma renders monocytes more sensitive to activation by IL-2. These results demonstrate that the IL-2Ralpha and IL-2Rbeta subunits are induced by different lymphokines through distinct mechanisms and that both receptor subunits can influence the response of monocytes to IL-2. C1 NCI,FREDERICK CANC RES DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FEDERICK CANC RES DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 FU NCI NIH HHS [N01-CO-74102] NR 37 TC 40 Z9 40 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 NOV 1 PY 1992 VL 149 IS 9 BP 2961 EP 2968 PG 8 WC Immunology SC Immunology GA JU748 UT WOS:A1992JU74800016 PM 1383334 ER PT J AU MAUVIEL, A REITAMO, S REMITZ, A LAPIERE, JC CESKA, M BAGGIOLINI, M WALZ, A EVANS, CH UITTO, J AF MAUVIEL, A REITAMO, S REMITZ, A LAPIERE, JC CESKA, M BAGGIOLINI, M WALZ, A EVANS, CH UITTO, J TI LEUKOREGULIN, A T-CELL-DERIVED CYTOKINE, INDUCES IL-8 GENE-EXPRESSION AND SECRETION IN HUMAN SKIN FIBROBLASTS - DEMONSTRATION OF ENHANCED NF-KAPPA-B BINDING AND NF-KAPPA-B-DRIVEN PROMOTER ACTIVITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NEUTROPHIL CHEMOTACTIC FACTOR; HUMAN DERMAL FIBROBLASTS; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; GROWTH-FACTOR-BETA; MESSENGER-RNA; FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; TRANSCRIPTION FACTOR; EPITHELIAL-CELLS AB It was shown previously that leukoregulin (LR), a T cell-derived cytokine with unique antitumor properties, modulates fibroblast functions in vitro, including prostaglandin production, matrix synthesis, and protease gene expression. Here, we have focused on the ability of LR to modulate IL-8 gene expression in human dermal fibroblasts. Using a specific ELISA, we demonstrated a dose-dependent enhancement of IL-8 production by LR, accompanied by a parallel elevation of the corresponding mRNA levels, as measured by Northern hybridizations. Maximum accumulation of IL-8 mRNA was observed after 6 h of incubation with LR, and the elevation persisted over 24 h. Inhibition of protein synthesis by cycloheximide resulted in superinduction of IL-8 mRNAs by LR. Dexamethasone, all-trans-retinoic acid, and TGF-beta1 failed to counteract the effect of LR on IL-8 gene expression. Transient cell transfections with an IL-8 promoter/CAT reporter gene construct showed a dose-dependent enhancement of the promoter activity by LR, suggesting transcriptional regulation. Gel shift assays with oligonucleotides containing the consensus NF-kappaB binding sequences of the IL-8 and Ig kappa light chain genes showed enhanced binding activity in nuclear extracts from cells incubated with LR. Transient transfection experiments using a NF-kappaB/SV2 promoter-CAT reporter gene construct showed enhanced CAT activity by LR. Taken together, these data suggest that LR may up-regulate IL-8 gene expression by activation of the binding of NF-kappaB to the corresponding cis-acting element in the IL-8 promoter. Our results demonstrate that LR, together with IL-1 and TNF-alpha, could participate in the recruitment of neutrophils to the sites of inflammation by induction of IL-8 production in fibroblasts. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL,233 S 10TH ST,ROOM 450,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,MOLEC DERMATOL SECT,PHILADELPHIA,PA 19107. SANDOZ GMBH,A-1235 VIENNA,AUSTRIA. UNIV BERN,THEODOR KOCHER INST,CH-3001 BERN,SWITZERLAND. NCI,DIV CANC ETIOL,TUMOR BIOL SECT,BIOL LAB,BETHESDA,MD 20892. RI MAUVIEL, Alain/F-6251-2013 FU NIAMS NIH HHS [T32-AR07561, AR-41439] NR 70 TC 18 Z9 18 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 NOV 1 PY 1992 VL 149 IS 9 BP 2969 EP 2976 PG 8 WC Immunology SC Immunology GA JU748 UT WOS:A1992JU74800017 PM 1401924 ER PT J AU LOBOS, E ONDO, A OTTESEN, EA NUTMAN, TB AF LOBOS, E ONDO, A OTTESEN, EA NUTMAN, TB TI BIOCHEMICAL AND IMMUNOLOGICAL CHARACTERIZATION OF A MAJOR IGE-INDUCING FILARIAL ANTIGEN OF BRUGIA-MALAYI AND IMPLICATIONS FOR THE PATHOGENESIS OF TROPICAL PULMONARY EOSINOPHILIA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPIRATORY-TRACT INFLAMMATION; EXCRETORY-SECRETORY PRODUCTS; T-CELL CLONES; SCHISTOSOMA-MANSONI; TRICHINELLA-SPIRALIS; QUALITATIVE CHARACTERIZATION; BRONCHOALVEOLAR LAVAGE; HELMINTH INFECTIONS; RESPONSES; ANTIBODY AB A major allergen of the human filarial parasite Brugia malayi has been identified by two-dimensional immunoblot analysis using a serum pool from patients with tropical pulmonary eosinophilia. The allergen is composed of two Ag with Mr 23 and Mr 25 and acidic isoelectric point (Bm23-25). Immunoblots using affinity-purified IgE antibodies to BM23-25 indicated that Bm23-25 is expressed mainly in the microfilarial stage. Digestion of the allergen with endoglycosidases indicates that it has N-linked oligosaccharide chains. Analysis of the reactivity of T cells derived from patients with lymphatic filariasis revealed that the Bm23-25 allergen was capable of stimulating T cell proliferation; Bm23-25 was also shown to induce IgE production in vitro from PBMC derived from patients with either TPE or other filarial symptoms. Bronchoalveolar lavage fluid of patients with TPE contained IgE antibodies that recognized Bm23-25 strongly, an observation suggesting that the microfilarial allergen might be involved in the pathogenesis of the TPE syndrome. C1 NIAID,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892. NR 65 TC 25 Z9 25 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 NOV 1 PY 1992 VL 149 IS 9 BP 3029 EP 3034 PG 6 WC Immunology SC Immunology GA JU748 UT WOS:A1992JU74800026 PM 1401928 ER PT J AU GIESE, T DAVIDSON, WF AF GIESE, T DAVIDSON, WF TI EVIDENCE FOR EARLY ONSET, POLYCLONAL ACTIVATION OF T-CELL SUBSETS IN MICE HOMOZYGOUS FOR LPR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MRL-LPR/LPR MICE; NECROSIS-FACTOR-ALPHA; MUTANT-GENE LPR; MP-IPR IPR; MONOCLONAL-ANTIBODY; INTERFERON-GAMMA; IFN-GAMMA; B-CELLS; AUTOIMMUNE MICE; LYMPHOPROLIFERATIVE DISORDERS AB Mice homozygous for lpr and gld develop profound lymphadenopathy characterized by the accumulation of two functionally anergic T cell subsets, a predominant B220+CD4-CD8- double negative (DN) population and a minor, closely related CD4 dull+ B220+ population. Lymph nodes from diseased lpr and gld mice also contain abnormally high numbers of conventional T cells, and we reported recently that a high proportion of lpr and gld CD4+B220- T cells have the hallmarks of primed or memory T cells. In the present study, we further investigated the extent, ontogeny, and possible causes of T cell activation in lpr and gld mice. The criteria used to identify primed or memory T cells included activation-dependent increases in the expression of CD44, LFA-1, and the early activation Ag, CD69, and decreases in the expression of Mel-14 and CD45RB, as well as quantitative differences in the in vitro production of IFN-gamma and the TNF-alpha by stimulated cells. A comparison of TCR Vbeta gene utilization by lpr T cell subsets also was undertaken. The results showed that T cell activation was widespread and complex. CD8+ T cells exhibited a similar pattern of activation to CD4+B220- T cells. The activation of these two subsets occurred in parallel, was in evidence by 4 to 6 wk of age, and was both chronic and progressive. The proportions of CD44(hi)LFA-1hi, CD4+B220-, and CD8+ T cells increased steadily between 4 and 20 wk of age, but changes in T cell growth, Mel-14, and CD45RB expression and cytokine secretion were not observed until mice were older than 11 wk. A very different pattern of activation was observed for B220+ T cells. At all ages, B220+ DN and CD4+B220+ T cells were CD44(hi)Mel-14hi and 60 to 75% were CD69+. The expression of CD69 appeared to be stimulus dependent rather than constitutive, suggesting that these cells, too, may be chronically stimulated in vivo. In keeping with their anergic state, DN T cells responded poorly to cross-linking of CD69. The stimuli inducing chronic activation of CD4+B220- and CD8+ T cells are unlikely to include inappropriate reactions to autoantigens because there was no evidence for selective accumulation of CD4+ or CD8+ T cells bearing particular Vbeta genes or potentially self-reactive cells that normally are deleted in the thymus. By comparison, C3H-lpr DN cells displayed some potentially significant differences in Vbeta6 and Vbeta9 expression from CD4+B220- and CD8+ T cells. Potential mechanisms leading to the progressive accumulation of primed T and B lymphocytes and B220+ T cells are discussed. C1 NCI,GENET LAB,BLDG 37,ROOM 2B13,BETHESDA,MD 20892. NR 70 TC 89 Z9 89 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 NOV 1 PY 1992 VL 149 IS 9 BP 3097 EP 3106 PG 10 WC Immunology SC Immunology GA JU748 UT WOS:A1992JU74800037 PM 1383337 ER PT J AU ULLMANN, CD SCHLOM, J GREINER, JW AF ULLMANN, CD SCHLOM, J GREINER, JW TI INTERLEUKIN-6 INCREASES CARCINOEMBRYONIC ANTIGEN AND HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN EXPRESSION ON THE SURFACE OF HUMAN COLORECTAL-CARCINOMA CELLS SO JOURNAL OF IMMUNOTHERAPY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; HUMAN 26-KD PROTEIN; COLON-CARCINOMA; RECOMBINANT INTERLEUKIN-6; INTERFERON ENHANCEMENT; MONOCLONAL-ANTIBODIES; ANTITUMOR-ACTIVITY; NECROSIS-FACTOR; MESSENGER-RNA; MURINE TUMOR AB Human colorectal carcinoma cells that were treated in vitro with interleukin-6 (IL-6) expressed increased levels of carcinoembryonic antigen (CEA) and normal histocompatibility leukocyte antigen (HLA) class I on their cell surface. The IL-6 mediated increase of CEA expression on the surface of a moderately differentiated colon carcinoma cell line (WiDr) was time- and dose-dependent. A 5-day treatment of the WiDr cells with 100 U IL-6/ml increased the percentage of cells that expressed CEA from 29 to >80% and enhanced the level of HLA class I expression. The increase in CEA expression as a result of IL-6 treatment was also observed using SDS-PAGE/Western blot analyses, and subsequent Northern blot analyses revealed concomitant increases in CEA-related mRNA transcripts. A comparison of the increases in CEA expression after IL-6, interferon-beta, and interferon-gamma on a nanomolar basis revealed that IL-6 was more potent than either of the interferons. Of 11 different human colorectal tumor cell lines that were treated with IL-6, CEA and/or HLA class I expression were increased in five. Thus, IL-6 can act directly on human colon carcinoma cells and selectively increase the expression of CEA and HLA class I antigens, which may provide some insight into the mechanisms involved in the ability of IL-6 to suppress in vivo tumor growth. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. NR 47 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1992 VL 12 IS 4 BP 231 EP 241 DI 10.1097/00002371-199211000-00003 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA JU243 UT WOS:A1992JU24300003 PM 1477074 ER PT J AU FUTAMI, H EADER, LA BACK, TT GRUYS, E YOUNG, HA WILTROUT, RH BAGULEY, BC AF FUTAMI, H EADER, LA BACK, TT GRUYS, E YOUNG, HA WILTROUT, RH BAGULEY, BC TI CYTOKINE INDUCTION AND THERAPEUTIC SYNERGY WITH INTERLEUKIN-2 AGAINST MURINE RENAL AND COLON CANCERS BY XANTHENONE-4-ACETIC ACID-DERIVATIVES SO JOURNAL OF IMMUNOTHERAPY LA English DT Article ID FLAVONE ACETIC-ACID; NATURAL-KILLER ACTIVITY; ADVANCED MALIGNANT-MELANOMA; POTENTIAL ANTITUMOR AGENTS; STRICT DOSE DEPENDENCY; HUMAN PERIPHERAL-BLOOD; INTERFERON ALPHA-BETA; CELL-ACTIVITY; FLAVONE-8-ACETIC ACID; GENE-EXPRESSION AB Derivatives of xanthenone-4-acetic acid (XAA) have been found to have similar activity to flavone-8-acetic acid against transplantable solid tumors. Some of these compounds were compared to flavone acetic acid (FAA) in their ability to induce cytokines as well as to mediate antitumor effects against murine renal cancer (Renca) and a mouse colon cancer (MCA-38). 5-Methyl-XAA and 5-chloro-XAA proved to be more potent than FAA on a mg/kg basis for induction of the genes for IFNalpha, IFNgamma, and TNFalpha, and for IFN and TNF activities in the sera of treated mice. These effects were sharply dose dependent. On the other hand, 7-methyl-XAA, which has no antitumor activity, did not induce these genes. In addition, 5-methyl-XAA and 5-chloro-XAA but not 7-methyl-XAA synergized with recombinant human interleukin-2 (rhIL-2) for the treatment of Renca and MCA-38. Doses of the active derivatives that failed to induce cytokines also exhibited no therapeutic synergy with rhIL-2. These results suggest that at least some of the antitumor effects of these XAA derivatives are related to their ability to induce cytokines. C1 NCI,FREDERICK CANC RES & DEV CTR,DCT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP INC,FREDERICK,MD 21701. UNIV AUCKLAND,SCH MED,CANC RES LAB,AUCKLAND,NEW ZEALAND. FU NCI NIH HHS [N01-CO-74102] NR 32 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1992 VL 12 IS 4 BP 247 EP 255 DI 10.1097/00002371-199211000-00005 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA JU243 UT WOS:A1992JU24300005 PM 1477076 ER PT J AU LANGE, JR RAUBITSCHEK, AA POCKAJ, BA SPENCER, WF LOTZE, MT TOPALIAN, SL YANG, JC ROSENBERG, SA AF LANGE, JR RAUBITSCHEK, AA POCKAJ, BA SPENCER, WF LOTZE, MT TOPALIAN, SL YANG, JC ROSENBERG, SA TI A PILOT-STUDY OF THE COMBINATION OF INTERLEUKIN-2-BASED IMMUNOTHERAPY AND RADIATION-THERAPY SO JOURNAL OF IMMUNOTHERAPY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; HIGH-DOSE INTERLEUKIN-2; ADVANCED CANCER AB A clinical trial was undertaken to evaluate the feasibility of combining radiation therapy and immunotherapy. Twenty-eight patients with metastatic cancer were treated with rapid fractionation radiation up to 2,000 cGy, followed within 24 h by a course of interleukin 2 (IL-2) at 720,000 IU/kg or tumor-infiltrating lymphocytes (TILs) and IL-2 at 720,000 IU/kg. All patients tolerated treatment without any apparent increase in toxicity referable to the irradiation. Four patients had significant shrinkage of tumor at the irradiated site. Only two patients showed significant tumor shrinkage both inside and outside of the irradiated field. While rapid fractionation radiation can be safely administered in combination with immunotherapy, we observed no apparent synergy in antitumor effect in this small number of patients. C1 NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 7 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV PY 1992 VL 12 IS 4 BP 265 EP 271 DI 10.1097/00002371-199211000-00007 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA JU243 UT WOS:A1992JU24300007 PM 1477077 ER PT J AU LAM, KS TITUS, JA DABRAH, TT KIMBALL, DL VEITCH, JM GUSTAVSON, DR COMPTON, BJ MATSON, JA FORENZA, S ROSS, J MILLER, D ROACH, J BEUTLER, J AF LAM, KS TITUS, JA DABRAH, TT KIMBALL, DL VEITCH, JM GUSTAVSON, DR COMPTON, BJ MATSON, JA FORENZA, S ROSS, J MILLER, D ROACH, J BEUTLER, J TI IMPROVED PROCESSES FOR THE PRODUCTION AND ISOLATION OF DYNEMICIN-A AND LARGE-SCALE FERMENTATION IN A 10000-LITER FERMENTER SO JOURNAL OF INDUSTRIAL MICROBIOLOGY LA English DT Article DE ANTITUMOR ANTIBIOTIC; DYNEMICIN-A; MICROMONOSPORA-CHERSINA ID POTENT ANTITUMOR ANTIBIOTICS; DNA; ESPERAMICINS; CLEAVAGE; FAMILY AB Supplementing the culture of Micromonospora chersina sp. nov. No. M956-1 with NaI (0. 5 mg/l) enhanced the production of dynemicin A by 35-fold in shake flask culture. Homogeneous dynemicin A was obtained from the whole broth extract by Dicalite chromatography, Scphadex LH-20 chromatography and vacuum liquid chromatography. Gram quantities of dynemicin A were obtained from the fermentation of M. chersina sp. nov. No. M956-1 in a 10000-liter fermentor. C1 BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,WALLINGFORD,CT. BRISTOL MYERS SQUIBB CO,DIV IND,SYRACUSE,NY. FREDERICK CANC RES & DEV CTR,FREDERICK,MD. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 14 TC 3 Z9 3 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0169-4146 J9 J IND MICROBIOL JI J. Indust. Microbiol. PD NOV PY 1992 VL 11 IS 1 BP 7 EP 12 DI 10.1007/BF01583725 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA KD923 UT WOS:A1992KD92300002 PM 1369016 ER PT J AU CLEMENS, JD SACK, DA RAO, MR CHAKRABORTY, J KHAN, MR KAY, B AHMED, F BANIK, AK VANLOON, FPL YUNUS, M HARRIS, JR AF CLEMENS, JD SACK, DA RAO, MR CHAKRABORTY, J KHAN, MR KAY, B AHMED, F BANIK, AK VANLOON, FPL YUNUS, M HARRIS, JR TI EVIDENCE THAT INACTIVATED ORAL CHOLERA VACCINES BOTH PREVENT AND MITIGATE VIBRIO-CHOLERAE O1 INFECTIONS IN A CHOLERA-ENDEMIC AREA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FIELD TRIAL; FOLLOW-UP; BANGLADESH; EFFICACY AB In a randomized, placebo-controlled field trial of B subunit-killed whole cell (BS-WC) and killed whole cell only (WC) inactivated oral cholera vaccines in rural Bangladesh, active surveillance of selected neighborhoods during the first year after vaccination identified 127 Vibrio cholerae O1 infections among 3285 three-dose recipients. For each vaccine, protective efficacy was greater against symptomatic (57%, P < .05 for BS-WC; 58%, P < .05 for WC) than against asymptomatic infections (46%, P < .05 for BS-WC; 32%, P = .09 for WC), and protection against each grade of infection was demonstrable for both the classical and El Tor biotypes. Although vaccine protection against symptomatic infections was evident in both young children and older persons, only persons vaccinated at age > 5 years were protected against asymptomatic infections. These results suggest that the inactivated oral vaccines acted both to protect against intestinal colonization by V. cholerae O1 and to interrupt the pathogenic sequence of established infections. C1 INT CTR DIARRHOEAL DIS RES,DHAKA,BANGLADESH. JOHNS HOPKINS UNIV,SCH PHYS NUCL,DEPT INT HLTH,BALTIMORE,MD 21218. CTR DIS CONTROL,DIV IMMUNIZAT,ATLANTA,GA 30333. CTR DIS CONTROL,DIV BACTERIAL ENTER DIS,ATLANTA,GA 30333. RP CLEMENS, JD (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,RM 640,EXECUT PL N,BETHESDA,MD 20892, USA. OI Harris, Jeffrey/0000-0001-8728-7195 NR 18 TC 26 Z9 26 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1992 VL 166 IS 5 BP 1029 EP 1034 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JV015 UT WOS:A1992JV01500011 PM 1402014 ER PT J AU STEIN, DS KORVICK, JA VERMUND, SH AF STEIN, DS KORVICK, JA VERMUND, SH TI STORAGE AS A FACTOR IN ENUMERATION OF CD4+ LYMPHOCYTES - REPLY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID FLOW-CYTOMETRY C1 NIAID,DIV AIDS,CLIN RES PROGRAM,MED & EPIDEMIOL BRANCHES,BETHESDA,MD 20892. NR 9 TC 0 Z9 0 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 NOV PY 1992 VL 166 IS 5 BP 1198 EP 1199 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JV015 UT WOS:A1992JV01500049 ER PT J AU ENK, AH KATZ, SI AF ENK, AH KATZ, SI TI EARLY EVENTS IN THE INDUCTION-PHASE OF CONTACT SENSITIVITY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL WORKSHOP ON LANGERHANS CELLS CY DEC 05-06, 1991 CL DALLAS, TX ID REGIONAL LYMPH-NODES; LANGERHANS CELLS; SENSITIZATION; MATURATION; MIGRATION AB After allergen application to skin, there is enhanced class II major histocompatibility complex antigen expression, as well as enhanced T-cell - stimulatory function by epidermal Langerhans cells (LC). In this study, we investigated the early changes in the epidermal cytokine profile using a sensitive reverse transcriptase PCR technique to determine whether cytokines may be related to LC activation. We found that, on the mRNA and protein level, changes in the epidermal cytokine pattern caused by allergens in the induction phase of contact sensitivity are distinct from those caused by irritants or tolerogens. The earliest of the changes is the LC-derived interleukin (IL) 1beta mRNA signal strength that is increased within 15 min of allergen painting. C1 NCI,DERMATOL BRANCH,BLDG 10,ROOM 12-N-238,BETHESDA,MD 20892. NR 10 TC 40 Z9 41 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1992 VL 99 IS 5 BP S39 EP S41 DI 10.1111/1523-1747.ep12668608 PG 3 WC Dermatology SC Dermatology GA JW928 UT WOS:A1992JW92800043 PM 1385542 ER PT J AU RIEGER, A WANG, B KILGUS, O OCHIAI, K MAURER, D FODINGER, D KINET, JP STINGL, G AF RIEGER, A WANG, B KILGUS, O OCHIAI, K MAURER, D FODINGER, D KINET, JP STINGL, G TI FC-EPSILON-RI MEDIATES IGE BINDING TO HUMAN EPIDERMAL LANGERHANS CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL WORKSHOP ON LANGERHANS CELLS CY DEC 05-06, 1991 CL DALLAS, TX ID ATOPIC-DERMATITIS; IMMUNOGLOBULIN-E; MAST-CELLS; RECEPTOR; ANTIGEN AB In a recent series of experiments, we observed that epidermal Langerhans cells (LC) of healthy, non-atopic individuals have the capacity of specifically binding monomeric serum or myeloma IgE. IgE-binding to LC could neither be prevented by pre-incubation of the cryostat sections with monoclonal antibodies (MoAb) against either FcepsilonRII/CD23 or FcgammaRII/CD32 nor by the addition of excess amounts of lactose, but could be entirely abrogated by pre-incubation with the anti-FcepsilonRI MoAb 15-1. A direct testing of the anti-FcepsilonRI MoAb 15-1 and 19-1 on cryostat sections in an indirect immuno-double-labeling technique showed that, in contrast to eight different anti-FcepsilonRII/CD23 MoAb, these MoAb react with the majority of CD1a-bearing epidermal cells. At an ultra-structural level, 15-1 immunogold-labeling in the epidermis was confined to the surface of cells exhibiting Birbeck granules. In further experiments, we were able to amplify by polymerase chain reaction (PCR) technology transcripts for the alpha,beta, and gamma chains of FcepsilonRI from LC-enriched epidermal cells and dermal cells, but not from LC-depleted epidermal cells. Transcripts for the mast cell enzyme tryptase were exclusively found in dermal cell - derived RNA preparations, thus excluding a contamination of the LC-enriched epidermal cell preparations by dermal mast cells. Collectively, these data show that epidermal LC, but no other epidermal cells, express FcepsilonRI molecules. C1 UNIV VIENNA,SCH MED,DEPT DERMATOL 1,DIV CUTANEOUS IMMUNOL,ALSER STR 4,A-1090 VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD. NR 17 TC 14 Z9 15 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1992 VL 99 IS 5 BP S30 EP S32 DI 10.1111/1523-1747.ep12668293 PG 3 WC Dermatology SC Dermatology GA JW928 UT WOS:A1992JW92800041 PM 1431205 ER PT J AU TANG, A UDEY, MC AF TANG, A UDEY, MC TI DOSES OF ULTRAVIOLET-RADIATION THAT MODULATE ACCESSORY CELL-ACTIVITY AND ICAM-1 EXPRESSION ARE ULTIMATELY CYTOTOXIC FOR MURINE EPIDERMAL LANGERHANS CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL WORKSHOP ON LANGERHANS CELLS CY DEC 05-06, 1991 CL DALLAS, TX ID ANTIGEN-PRESENTING CELLS; PHOTOIMMUNOLOGY; LYMPHOCYTES; MECHANISMS; INVITRO AB Mechanisms that underlie immunomodulatory properties of ultraviolet (UV) radiation remain incompletely characterized. Recently, we have studied effects of UV on the functional activity of epidermal Langerhans cells (LC) and have attempted to relate inhibitory effects of UV on LC function to modulatory effects of UV on adhesion molecule expression by LC. Exposure of LC in vitro to amounts of UVB, UVC, or psoralen + UVA (PUVA) radiation that inhibited LC function also prevented increased expression of intercellular adhesion molecule-1 by LC in vitro. Subsequent studies revealed that amounts of UV radiation that inhibited LC function and modulated ICAM-1 expression also decreased LC survival in vitro, although UV-induced LC cytotoxicity did not become apparent until 48 - 72 h after UV exposure. Our results are consistent with those of previous studies that suggested that low doses of UV radiation were cytotoxic for LC in situ. The potential cytotoxicity of UV radiation for LC should be considered when studies of effects of UV radiation on immune responses in skin are interpreted. C1 NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N254,BETHESDA,MD 20892. NR 16 TC 17 Z9 19 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1992 VL 99 IS 5 BP S71 EP S73 PG 3 WC Dermatology SC Dermatology GA JW928 UT WOS:A1992JW92800054 PM 1358982 ER PT J AU PELEG, I LUDOWYKE, RI BEAVEN, MA ADELSTEIN, RS AF PELEG, I LUDOWYKE, RI BEAVEN, MA ADELSTEIN, RS TI THE ROLE OF MYOSIN PHOSPHORYLATION IN RBL-2H3 CELL SECRETION SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID PROTEIN-KINASE-C; HEAVY-CHAIN; MESSENGER-RNA; SERINE; IDENTIFICATION; EXPRESSION; SEQUENCE C1 NHLBI,MOLEC CARDIOL LAB,BLDG 10,ROOM 8N-202,BETHESDA,MD 20892. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. OI Adelstein, Robert/0000-0002-8683-2144 NR 17 TC 4 Z9 4 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 NOV PY 1992 VL 120 IS 5 BP 675 EP 680 PG 6 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA JX759 UT WOS:A1992JX75900003 PM 1385555 ER PT J AU ORTALDO, JR WINKLERPICKETT, RT NAGASHIMA, K YAGITA, H OKUMURA, K AF ORTALDO, JR WINKLERPICKETT, RT NAGASHIMA, K YAGITA, H OKUMURA, K TI DIRECT EVIDENCE FOR RELEASE OF PORE-FORMING PROTEIN DURING NK CELLULAR LYSIS SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE MECHANISM OF LYSIS; NATURAL KILLER CELLS; POREFORMING PROTEIN ID ACTIVATED KILLER CELLS; NATURAL-KILLER; TARGET-CELLS; GOLGI-APPARATUS; CYTO-TOXICITY; LYMPHOCYTES-T; POLARIZATION; MECHANISM; GRANULES AB In the present study, we have examined the exocytosis model for cellular lysis. Using monoclonal antibodies reactive with human pore-forming protein (PFP), we examined the localization of PFP at the interaction site of natural killer (NK) cells and the NK tumor targets K562 and Molt-4 as well as during antibody-dependent cellular cytotoxicity. Following the interaction of effector-target cell contact, an increased frequency of PFP was detected on the effector surface, in the microenvironment, and on the target surface of the interaction site. This temporal deposition of PFP was paralleled by loss of target cell integrity and release of chromium. In addition, selective deposition of PFP was seen at the interaction site of the target cell compared to other target cell regions. Collectively, these results are consistent with the exocytosis model and further support the hypothesis that PFP is one of the secreted moieties involved in NK cellular cytotoxicity. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21701. JUNTENDO UNIV,SCH MED,DEPT IMMUNOL,TOKYO 113,JAPAN. RP ORTALDO, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK CANC RES FACIL,DIV CANC TREATMENT,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 22 TC 23 Z9 25 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 1992 VL 52 IS 5 BP 483 EP 488 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA JY433 UT WOS:A1992JY43300002 PM 1431558 ER PT J AU LOHSE, P BREWER, HB MENG, MS SKARLATOS, SI LAROSA, JC BREWER, HB AF LOHSE, P BREWER, HB MENG, MS SKARLATOS, SI LAROSA, JC BREWER, HB TI FAMILIAL APOLIPOPROTEIN-E DEFICIENCY AND TYPE-III HYPERLIPOPROTEINEMIA DUE TO A PREMATURE STOP CODON IN THE APOLIPOPROTEIN-E GENE SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ATHEROSCLEROSIS; DYSBETALIPOPROTEINEMIA; NONSENSE MUTATION; LIPOPROTEIN METABOLISM ID LOW-DENSITY LIPOPROTEIN; RECEPTOR-BINDING; AQUEOUS-SOLUTION; APOE DEFICIENCY; MESSENGER-RNA; CHOLESTEROL; PROTEIN; ACID; SITE; ELECTROPHORESIS AB A kindred with apolipoprotein E deficiency and a truncated lower molecular weight apoE mutant, designated apoE-3Washington, has been identified. Gel electrophoresis demonstrated complete absence of the normal apoE isoproteins and the presence of a small quantity of a lower molecular weight apoE. Plasma apoE levels in the proband were approximately 4% of normal. This marked deficiency of apoE resulted in delayed uptake of chylomicron and very low density lipoprotein (VLDL) remnants by the liver, elevated plasma cholesterol levels, mild hypertriglyceridemia, and the development of type III hyperlipoproteinemia. Sequence analysis of the patient's apoE gene revealed a single nucleotide substitution of an A for a G, which converted amino acid 210 of the mature protein, tryptophan (TGG), to a premature chain termination codon (TAG), thus leading to the synthesis of a truncated E apolipoprotein of 209 amino acids with a molecular mass of 23.88 kDa. Northern blot analysis of differentiated monocyte-derived macrophages demonstrated a mutant mRNA indistinguishable in size from normal apoE mRNA. The nucleotide substitution also resulted in the formation of a new restriction site for Mae I. Using this enzyme we were able to establish that the proband is a homozygote and that her two offsprings are heterozygous for the epsilon-3Washington allele. These data demonstrate that the striking deficiency of apoE-3Washington results in a moderate form of type III hyperlipoproteinemia. The clinical presentation also suggests a dispensable role of apoE in the nervous system and in immunoregulation. C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. RP LOHSE, P (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 42 TC 32 Z9 32 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 1992 VL 33 IS 11 BP 1583 EP 1590 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW924 UT WOS:A1992JW92400002 PM 1361196 ER PT J AU PAWLOSKY, RJ SPRECHER, HW SALEM, N AF PAWLOSKY, RJ SPRECHER, HW SALEM, N TI HIGH-SENSITIVITY NEGATIVE-ION GC-MS METHOD FOR DETECTION OF DESATURATED AND CHAIN-ELONGATED PRODUCTS OF DEUTERATED LINOLEIC AND LINOLENIC ACIDS SO JOURNAL OF LIPID RESEARCH LA English DT Article DE PENTAFLUOROBENZYL ESTERS; DEUTERATED LINOLEIC AND LINOLENIC ACID; GC-MS; NCI; DESATURATION AB A sensitive negative chemical ionization (NCI) gas chromatography-mass spectrometry (GC-MS) method for the detection of pentafluorobenzyl (PFB) esters of deuterated fatty acids is described. Deuterated linoleic [18:2n-6 H-2(4)-9,10,12,13] and linolenic [18:3n-3 H-2(5)-17,17,18,18,18] acids were converted to chain-elongated and desaturated products during incubations with homogenates prepared from rat liver. The extracted fatty acids were derivatized with pentafluorobenzyl bromide and analyzed in the negative ion mode by GC-MS. The detection limit of the PFB esters in NCI using selected ion monitoring was below 10 femtograms. In general, detection of the PFB derivatives using the negative ion mode was more than three orders of magnitude more sensitive than using a positive chemical ionization (PCI) method with methyl ester derivatives. The PFB esters of the H-2(4)-18:2n-6 metabolites eluted with their unlabeled analogues, whereas the PFB esters of the H-2(5)-18:3n-3 metabolites were resolved from the unlabeled compounds on polar capillary FFAP columns. Isotope ratios of the H-2(4)-18:2n-6 metabolites were used to quantify the deuterated compounds from standard dilution curves generated from the ion abundances of the unlabeled fatty acids. The H-2(5)-18:3n-3 metabolites were quantified similarly using 18:3n-3. This method is feasible for the study of the in vivo metabolism of deuterated essential fatty acids in whole animals. C1 NIAAA,DICBR,CLIN SCI LAB,ANALYT CHEM SECT,BLDG 10,ROOM 3C-102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. OHIO STATE UNIV,DEPT PHYSIOL CHEM,COLUMBUS,OH 43210. NR 8 TC 60 Z9 61 U1 0 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 1992 VL 33 IS 11 BP 1711 EP 1717 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW924 UT WOS:A1992JW92400015 PM 1464754 ER PT J AU RUIZCABELLO, J VUISTER, GW MOONEN, CTW VANGELDEREN, P COHEN, JS VAN ZIJL, PCM AF RUIZCABELLO, J VUISTER, GW MOONEN, CTW VANGELDEREN, P COHEN, JS VAN ZIJL, PCM TI GRADIENT-ENHANCED HETERONUCLEAR CORRELATION SPECTROSCOPY - THEORY AND EXPERIMENTAL ASPECTS SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article C1 GEORGETOWN UNIV, SCH MED, DEPT PHARMACOL, ROCKVILLE, MD 20850 USA. NIDDKD, CHEM PHYS LAB, BETHESDA, MD 20892 USA. NCRR, BEIP, INVIVD NMR RES CTR, BETHESDA, MD 20892 USA. DELFT UNIV TECHNOL, DEPT PHYS, DELFT, NETHERLANDS. RI van Zijl, Peter/B-8680-2008; Moonen, Chrit/K-4434-2016; OI Moonen, Chrit/0000-0001-5593-3121; Ruiz-Cabello, Jesus/0000-0001-8681-5056 NR 47 TC 228 Z9 229 U1 1 U2 8 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 1992 VL 100 IS 2 BP 282 EP 302 DI 10.1016/0022-2364(92)90262-6 PG 21 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA JY558 UT WOS:A1992JY55800005 ER PT J AU SCHWAN, TG AF SCHWAN, TG TI XENOPSYLLA-BANTORUM IS AN EAST-AFRICAN SUBSPECIES OF X-CHEOPIS (SIPHONAPTERA, PULICIDAE) SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE XENOPSYLLA-BANTORUM; XENOPSYLLA-CHEOPIS; TAXONOMY ID FLEAS AB The geographic distribution, host association, and male genital morphology of Xenopsylla bantorum Jordan were examined and compared with the Nilotic and Oriental "strains" of Xenopsylla cheopis (Rothschild). The more acute shape of the ninth sternite separates X. bantorum from all types of X. cheopis; however, the length of the first process of the male's clasper and the number of setae on this process are significantly different among all three groups; the Nilotic strain of X. cheopis is intermediate to the others. Specimens collected from both wild and commensal rodents in Nakuru, Kenya, were all X. bantorum, suggesting that X. cheopis present early in the century that resulted from introductions on Rattus rattus had been absorbed by the native X. bantorum population. These factors and a review of opinions by others concerning the status of X. bantorum demonstrate that this flea is not specifically distinct from X. cheopis. The trinomial X. cheopis bantorum is erected. Furthermore, the Nilotic and Oriental "strains" of X. cheopis are distinguishable morphologically solely by the length of the male's first process. RP SCHWAN, TG (reprint author), NIAID,ARTHROPOD BORNE DIS SECT,VECTORS & PATHOGENS LAB,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 36 TC 6 Z9 7 U1 0 U2 1 PU ENTOMOL SOC AMER PI LANHAM PA 9301 ANNAPOLIS RD, LANHAM, MD 20706 SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD NOV PY 1992 VL 29 IS 6 BP 927 EP 933 PG 7 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA JW623 UT WOS:A1992JW62300005 PM 1460630 ER PT J AU ARISPE, N POLLARD, HB ROJAS, E AF ARISPE, N POLLARD, HB ROJAS, E TI CALCIUM-INDEPENDENT K+-SELECTIVE CHANNEL FROM CHROMAFFIN GRANULE MEMBRANES SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE CHROMAFFIN GRANULE; K+ CHANNEL; PLANAR BILAYERS CHANNEL RECONSTITUTION ID ADRENAL-MEDULLARY CELLS; SYNAPTIC VESICLES; CHARYBDOTOXIN BLOCK; TRANSMITTER RELEASE; SECRETORY VESICLES; BILAYER-MEMBRANES; EXOCYTOSIS; PROTEIN; ATP; PH AB Intact adrenal chromaffin granules and purified granule membrane ghosts were allowed to fuse with acidic phospholipid planar bilayer membranes in the presence of Ca2+ (1 mm). From both preparations, we were able to detect a large conductance potassium channel (ca. 160 pS in symmetrical 400 mm K+), which was highly selective for K+ over Na+ (P(K)/P(Na) = 11) as estimated from the reversal potential of the channel current. Channel activity was unaffected by charybdotoxin, a blocker of the [Ca2+]-activated K+ channel of large conductance. Furthermore, this channel proved quite different from the previously described channels from other types of secretory vesicle preparations, not only in its selectivity and conductance, but also in its insensitivity to both calcium and potential across the bilayer. We conclude that the chromaffin granule membrane contains a K+-selective channel with large conductance. We suggest that the role of this channel may include ion movement during granule assembly or recycling, and do not rule out events leading to exocytosis. RP ARISPE, N (reprint author), NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 55 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD NOV PY 1992 VL 130 IS 2 BP 191 EP 202 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA JZ745 UT WOS:A1992JZ74500008 PM 1283986 ER PT J AU RALL, JE AF RALL, JE TI RESEARCH FRAUD IN THE BEHAVIORAL AND BIOMEDICAL SCIENCES - MILLER,DJ, HERSEN,M SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP RALL, JE (reprint author), NIH,WASHINGTON,DC, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1992 VL 180 IS 11 BP 739 EP 739 DI 10.1097/00005053-199211000-00017 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JY190 UT WOS:A1992JY19000015 ER PT J AU MASSA, PT HIRSCHFELD, S LEVI, BZ QUIGLEY, LA OZATO, K MCFARLIN, DE AF MASSA, PT HIRSCHFELD, S LEVI, BZ QUIGLEY, LA OZATO, K MCFARLIN, DE TI EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-I GENES IN ASTROCYTES CORRELATES WITH THE PRESENCE OF NUCLEAR FACTORS THAT BIND TO CONSTITUTIVE AND INDUCIBLE ENHANCERS SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE ASTROCYTE; MAJOR HISTOCOMPATIBILITY COMPLEX; ENHANCER; REGULATION; CLASS-I; TRANSCRIPTION ID NF-KAPPA-B; INTERFERON-INDUCED TRANSCRIPTION; TISSUE-SPECIFIC EXPRESSION; REGULATORY ELEMENT; BRAIN-CELLS; GEL-ELECTROPHORESIS; POSITIVE REGULATOR; CONSENSUS SEQUENCE; RESPONSE SEQUENCE; VIRAL PERSISTENCE AB The molecular basis of constitutive and inducible major histocompatibility complex (MHC) class I gene expression was studied in murine astrocytes in primary culture. Astrocytes constitutively expressed MHC class I molecules and treatment of these cells with interferon-gamma (IFN-gamma) further induced expression. The conserved region containing the upstream MHC class I regulatory element (MHC-CRE) and juxtaposed interferon consensus sequence (ICS) enhanced constitutive MHC class I promoter activity. As seen with cell surface expression of MHC molecules, treatment of astrocytes with IFN-gamma increased MHC class I promoter activity. Inducible expression required the presence of the MHC-CRE/ICS enhancer region. Nuclear factors that bind to the MHC-CRE and ICS were constitutively expressed in cultured astrocytes and IFN-gamma treatment further induced binding activity both to the MHC-CRE and ICS and correlated with induction of MHC class I gene expression. This study identifies the MHC-CRE and ICS as the major cis elements in controlling MHC class I promoter activity and suggests that the expression of nuclear factor binding activities to these enhancer elements is a basic transactivating mechanism for the expression of MHC class I genes in astrocytes. C1 NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. RP MASSA, PT (reprint author), SUNY HLTH SCI CTR,DEPT NEUROL,750 E ADAMS ST,SYRACUSE,NY 13210, USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 57 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD NOV PY 1992 VL 41 IS 1 BP 35 EP 42 DI 10.1016/0165-5728(92)90193-O PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA KB861 UT WOS:A1992KB86100006 PM 1460091 ER PT J AU BODENTEICH, A MITCHELL, LG MERRIL, CR MILLER, BE GHANBARI, HA HEEGAARD, NHH AF BODENTEICH, A MITCHELL, LG MERRIL, CR MILLER, BE GHANBARI, HA HEEGAARD, NHH TI IMMUNOCHEMICAL CHARACTERIZATION OF A MONOCLONAL-ANTIBODY SPECIFIC FOR ALZHEIMERS-DISEASE ASSOCIATED PROTEIN SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE ALZHEIMERS DISEASE; MONOCLONAL ANTIBODY; DISSOCIATION CONSTANT; DEPHOSPHORYLATION; CROSSED AFFINITY ELECTROPHORESIS; TAU; ALZHEIMERS DISEASE ASSOCIATED PROTEIN ID HUMAN BRAIN-TISSUE; TAU-PROTEINS; ANTIGEN; TANGLES; ALZ-50 AB In this study, the monoclonal antibody PHF-1 which recognizes epitopes unique to Alzheimer's disease associated proteins (ADAP) has been characterized. Crossed affinity immunelectrophoresis was used to estimate the binding constant for the interaction of PHF-1 with ADAP and to estimate the fraction of PHF-1 reactive protein. The binding constant of PHF-1 was determined to be 1.3 X 10(-8) M. Furthermore, the effect of dephosphorylation on the electrophoretic pattern of the PHF-I reactive protein and the ensuing changes in its immunoreactivity were demonstrated. C1 NIMH,BIOCHEM GENET LAB,WASHINGTON,DC 20032. ABBOTT LABS,ABBOTT PK,IL. NIDR,CELLULAR DEV & ONCOL LAB,PEPTIDE & IMMUNOCHEM UNIT,BETHESDA,MD 20892. RP BODENTEICH, A (reprint author), UNIV OKLAHOMA,DEPT CHEM & BIOCHEM,620 PARRINGTON OVAL,ROOM 208,NORMAN,OK 73019, USA. NR 26 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD NOV PY 1992 VL 41 IS 1 BP 111 EP 115 DI 10.1016/0165-5728(92)90202-V PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA KB861 UT WOS:A1992KB86100015 PM 1460088 ER PT J AU HECKMAN, CJ WEYTJENS, JLF LOEB, GE AF HECKMAN, CJ WEYTJENS, JLF LOEB, GE TI EFFECT OF VELOCITY AND MECHANICAL HISTORY ON THE FORCES OF MOTOR UNITS IN THE CAT MEDIAL GASTROCNEMIUS-MUSCLE SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID THIXOTROPIC BEHAVIOR; TIBIALIS POSTERIOR; SKELETAL-MUSCLE; ISOMETRIC FORCE; FIBERS; HINDLIMB; TENSION; SOLEUS; LOCOMOTION; STIFFNESS AB 1. Two fundamental aspects of the dynamic behavior of motor units of the cat medial gastrocnemius (MG) muscle were measured. Force-velocity (FV) relationships were measured with the use of constant velocity shortening and lengthening movements. Effects of mechanical history were assessed via comparisons of forces immediately after or during slow movements with standard isometric forces. Isometric force-length (FL) relations were also measured, and the effect of different stimulation rates on both FV and FL data was assessed. 2. Prior or concurrent movement greatly potentiated motor-unit force, but this movement potentiation was highly dependent on the amplitude of the unit's force. The smallest twitch forces of type S units (< 10 mN) were potentiated more than threefold, but no potentiation occurred for unit forces > 200 mN. It was tentatively concluded that movement potentiation may play little role in normal movements because it does not occur at forces > 1 % of maximal isometric force of the MG. 3. During shortening, the normalized FV relations of type S units were relatively steeper than those of type FR or FF units. For lengthening, there was no evident relation between FV steepness and motor-unit type. 4. Stimulation rate affected both the FV and FL relationships of the motor units. The peak of the FL relationship (L(o)) clearly shifted to shorter muscle lengths as stimulation rate was increased. The steepness of the FV relationship for shortening was decreased by increasing stimulation rate, but this effect was modest. 5. The shift in motor-unit L(o) and the differences in motor-unit FV relationships were hypothesized to play significant roles during normal motor behavior. Realistic computer simulations of FL and FV functions for a population of motor units undergoing normal steady-state recruitment and rate modulation supported these hypotheses. As the level of simulated neural drive increased, the population L(o) shifted to considerably shorter lengths, and the normalized FV function became much less steep. The significance of these results for models of muscle are discussed. C1 NIH,NEURAL CONTROL LAB,BETHESDA,MD 20814. FU NINDS NIH HHS [NS-08210] NR 57 TC 20 Z9 20 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1992 VL 68 IS 5 BP 1503 EP 1515 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA JY685 UT WOS:A1992JY68500003 PM 1479427 ER PT J AU ZEE, DS FITZGIBBON, EJ OPTICAN, LM AF ZEE, DS FITZGIBBON, EJ OPTICAN, LM TI SACCADE-VERGENCE INTERACTIONS IN HUMANS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TERM NONCONJUGATE ADAPTATION; EYE-MOVEMENTS; ANISOMETROPIC SPECTACLES; OCULAR VERGENCE; BINOCULAR COORDINATION; NATURAL CONDITIONS; VERTICAL SACCADES; ADAPTIVE-CHANGES; NYSTAGMUS; VELOCITY AB 1. We recorded eye movements in four normal human subjects during refixations between targets calling for various combinations of saccades and vergence. We confirmed and extended prior observations of 1) transient changes in horizontal ocular alignment during both pure horizontal saccades (relative divergence followed by relative convergence) and pure vertical saccades (usually divergence for upward and convergence for downward saccades); 2) occasional, high-frequency (20-25 Hz), conjugate oscillations along the axis orthogonal to the main saccade; and 3) the speeding up of horizontal vergence by both horizontal and vertical saccades. 2. To interpret these findings, we developed a hypothesis for the generation of vergence to step changes in target depth, both with and without associated saccades. The essential features of this hypothesis are 1) the transient changes in horizontal ocular alignment during pure horizontal saccades reflect asymmetries in the mechanical properties of the lateral and medial rectus muscles causing adduction to lag abduction; 2) pure vergence movements in response to step changes in target depth are generated by a neural network that uses a desired change in vergence position as its input command and instantaneous vergence motor error (the difference between the desired change and the actual change in vergence) to drive vergence premoter neurons; and 3) the facilitation of horizontal vergence by saccades arises from nonlinear interactions in central premotor circuits. 3. The hypothetical network for generating pure vergence to step changes in target depth is analogous in structure to the local feedback model for the generation of saccades and has the same conceptual appeal. With the assumption of a single nonlinearity describing the relationship between a vergence motor error signal and the output of the neurons that generate promoter vergence velocity commands, this model generates pure vergence movements with peak velocity-amplitude relationships and trajectories that closely match those of experimental data. 4. Several types of models are proposed for the central, nonlinear interaction that occurs when saccades and vergence are combined. Common to all models is the idea that omnidirectional pause neurons (OPN), which are thought to gate activity for saccade burst neurons, also gate activity for saccade-related vergence. In one model we hypothesize the existence of a separate class of saccade-related vergence burst neurons, which generate premotor horizontal vergence commands but only during saccades. In a second model we hypothesize separate right eye and left eye saccadic burst neurons that receive not only conjugate, but also equal but oppositely directed vergence error signals. In this way the difference between the outputs of the right eye and left eye saccade burst neurons produces a saccade-related horizontal vergence command. In a third model we propose that facilitation of vergence during saccades is a result of a multiplication (an increase in the gain of premotor vergence velocity neurons selectively during saccades). 5. The results of simulations of these models and comparison with our experimental data favor the first and third models, which either incorporate a separate class of saccade-related vergence burst neurons, or assume a change in property of premotor vergence velocity neurons caused by the lifting of OPN inhibition during saccades. Simulations of these models lead to a number of predictions about the properties of neurons within the brain stem that generate vergence commands, both with and without associated saccades. Electrophysiological experiments are needed to confirm or refute these hypotheses. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. FU NEI NIH HHS [EY-01849] NR 47 TC 234 Z9 237 U1 3 U2 14 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1992 VL 68 IS 5 BP 1624 EP 1641 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA JY685 UT WOS:A1992JY68500012 PM 1479435 ER PT J AU GREEN, MV BACHARACH, SL BORER, JS BONOW, RO AF GREEN, MV BACHARACH, SL BORER, JS BONOW, RO TI 1ST-PASS VERSUS GATED EQUILIBRIUM RADIOANGIOGRAPHY - REPLY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter C1 NEW YORK HOSP,NEW YORK,NY 10021. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. RP GREEN, MV (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 1992 VL 33 IS 11 BP 2057 EP 2058 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JW929 UT WOS:A1992JW92900038 ER PT J AU MAX, MB ZEIGLER, D SHOAF, SE CRAIG, BE BENJAMIN, J LI, SH BUZZANELL, C PEREZ, M GHOSH, BC AF MAX, MB ZEIGLER, D SHOAF, SE CRAIG, BE BENJAMIN, J LI, SH BUZZANELL, C PEREZ, M GHOSH, BC TI EFFECTS OF A SINGLE ORAL DOSE OF DESIPRAMINE ON POSTOPERATIVE MORPHINE ANALGESIA SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE ANALGESICS; ANALGESIA; NARCOTICS; MORPHINE; PAIN; POSTOPERATIVE PAIN; DESIPRAMINE; ANTIDEPRESSIVE AGENTS; NOREPINEPHRINE; CLINICAL TRIALS AB Drugs that block norepinephrine reuptake offer promise as opioid potentiators, because norepinephrine mediates opioid analgesia but not side effects such as sedation or nausea. In a two-by-two factorial design, we randomized 62 inpatients with pain following major surgery to receive either desipramine, 50 mg by mouth, or placebo at 6 a.m. on the first day after surgery. At their first request of pain medication after 8 a.m., they were given intravenous morphine, either 0.033 mg/kg or 0.10 mg/kg. Pain relief and side effects were assessed for 4 hr; peak relief on the visual analog scale (VAS) was the primary outcome variable. Pain relief, side effect scores, and time to remedication were significantly greater with the higher dose than with the lower dose of morphine, verifying assay sensitivity, but desipramine pretreatment did not significantly enhance morphine analgesia. The mean increase in peak VAS relief score after desipramine pretreatment, relative to placebo, was 6%; the 95% confidence interval for this estimate ranged from a 21% reduction to a 34% increase in pain relief. These results differ from a previous report that 1 week of pretreatment with desipramine, 75 mg per day, potentiated postoperative morphine analgesia. We conclude that if desipramine potentiation of opioid analgesia occurs in humans, its demonstration may require higher doses or chronic treatment. RP MAX, MB (reprint author), NIDR,PAIN RES CLIN,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 10,ROOM 3C-405,BETHESDA,MD 20892, USA. NR 0 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 1992 VL 7 IS 8 BP 454 EP 462 DI 10.1016/0885-3924(92)90131-Z PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA KA811 UT WOS:A1992KA81100004 PM 1287107 ER PT J AU MCNAMARA, MJ ALEXANDER, HR NORTON, JA AF MCNAMARA, MJ ALEXANDER, HR NORTON, JA TI CYTOKINES AND THEIR ROLE IN THE PATHOPHYSIOLOGY OF CANCER CACHEXIA SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article; Proceedings Paper CT SYMP ON NUTRITION AND CANCER : CRITICAL ISSUES IN BASIC SCIENCE AND CLINICAL RESEARCH CY JAN, 1992 CL ORLANDO, FL SP AMER SOC PARENTAL & ENTERAL NUTR, NIH ID TUMOR-NECROSIS-FACTOR; LEUKEMIA-INHIBITORY FACTOR; TOTAL PARENTERAL-NUTRITION; FACTOR-ALPHA; PROTEIN-METABOLISM; COLORECTAL-CANCER; GAMMA-INTERFERON; BEARING RATS; LUNG-CANCER; CACHECTIN AB Cancer cachexia describes a syndrome that consists of weight loss, and abnormalities in carbohydrate, protein, and lipid metabolism, which result in a state of persistent net negative energy balance. Patients suffering from cancer cachexia have a significantly shortened survival after cancer treatment. Recent experimental studies have focused on the belief that the mechanisms of cancer cachexia involve the host's production of inflammatory cytokines, which through broad physiologic actions ultimately lead to a chronic state of wasting, malnourishment, and death. Cytokines that have been thought to play a role in the pathophysiology of cachexia include tumor necrosis factor, interleukin-1, interleukin-6, interferon-gamma and differentiation factor. It has become clear that these cytokines have overlapping physiologic activities, which makes it likely that no single substance is the sole cause of cachexia in most cancer patients. Only further investigation may make it possible to more clearly define the role of cytokines in the pathophysiology of cancer cachexia. Specific strategies to reverse the cachectic effects of these substances may then be developed to ultimately improve cancer treatment. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. NR 62 TC 59 Z9 60 U1 1 U2 3 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD NOV-DEC PY 1992 VL 16 IS 6 SU S BP S50 EP S55 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JY964 UT WOS:A1992JY96400003 PM 1287224 ER PT J AU LEWIS, LL BUTLER, KM HUSSON, RN MUELLER, BU FOWLER, CL STEINBERG, SM PIZZO, PA AF LEWIS, LL BUTLER, KM HUSSON, RN MUELLER, BU FOWLER, CL STEINBERG, SM PIZZO, PA TI DEFINING THE POPULATION OF HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN AT RISK FOR MYCOBACTERIUM-AVIUM-INTRACELLULARE INFECTION SO JOURNAL OF PEDIATRICS LA English DT Article ID IMMUNE-DEFICIENCY-SYNDROME; COMPLEX INFECTION; AIDS PATIENTS; BACTEREMIA; SURVIVAL; THERAPY AB We reviewed the 22 cases of Mycobacterium avium-intracellulare (MAI) infection that occurred among 196 human immunodeficiency virus-infected children seen at the National Cancer Institute Pediatric Branch from December 1986 through April 1991, and an additional 65 charts from children with cultures negative for MAI. All patients with proven MAI were receiving antiretroviral therapy with zidovudine, dideoxyinosine, or a combination of zidovudine and dideoxycytidine. All patients had disseminated MAI infection, except one adolescent who had only evidence of localized lymphadenitis. All cases of MAI but one were diagnosed before death. The overall incidence of MAI was 11% in our patients but increased to 24% in patients whose absolute CD4 cell counts were <100 cells/mm3. Symptoms most commonly associated with MAI infection included recurrent fever (86% of patients), weight loss or failure to thrive (64%), neutropenia (55%), night sweats (32%), and abdominal pain (27%). Children infected with MAI had a mean CD4 percentage of 2% (range, 0% to 7%) and a mean absolute CD4 count of 12 cells/mm3 (range, 0 to 48 cells/mm3), significantly lower than in the remainder of the clinic population or the group of children with cultures negative for MAI. Of 20 patients with MAI infection who were tested, 10 had measurable p24 antigen with a mean value 939 pg/ml (range, 77 to 3270 pg/ml) compared with 19 of 59 patients without MAI infection in whom the mean positive value was 413 pg/ml. There was no difference in survival time between those children with documented MAI infection (median survival time, 45.5 weeks) and those with similarly low CD4 counts and cultures negative for MAI (median survival time, 50.4 weeks). Future improvements in therapeutic options may make screening of pediatric human immunodeficiency virus-infected patients with low CD4 counts a reasonable plan. C1 NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. NCI, WARREN G MAGNUSON CLIN CTR, DIAGNOST MICROBIOL LAB, BETHESDA, MD 20892 USA. RP LEWIS, LL (reprint author), NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 27 TC 46 Z9 47 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 1992 VL 121 IS 5 BP 677 EP 683 DI 10.1016/S0022-3476(05)81892-X PN 1 PG 7 WC Pediatrics SC Pediatrics GA JY695 UT WOS:A1992JY69500002 PM 1432413 ER PT J AU MUELLER, BU JACOBSEN, F BUTLER, KM HUSSON, RN LEWIS, LL PIZZO, PA AF MUELLER, BU JACOBSEN, F BUTLER, KM HUSSON, RN LEWIS, LL PIZZO, PA TI COMBINATION TREATMENT WITH AZIDOTHYMIDINE AND GRANULOCYTE COLONY-STIMULATING FACTOR IN CHILDREN WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF PEDIATRICS LA English DT Article ID AIDS-RELATED COMPLEX; CONTROLLED TRIAL; NEUTROPENIA; ZIDOVUDINE; CHEMOTHERAPY; CANCER; AZT AB Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 X 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 X 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 mug/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT. C1 NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, BETHESDA, MD 20892 USA. NR 21 TC 33 Z9 33 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 1992 VL 121 IS 5 BP 797 EP 802 DI 10.1016/S0022-3476(05)81918-3 PN 1 PG 6 WC Pediatrics SC Pediatrics GA JY695 UT WOS:A1992JY69500027 PM 1279153 ER PT J AU SUH, HH HUDSON, P FANNIN, R BOULOM, K MCMILLIAN, MK POISNER, AM HONG, JS AF SUH, HH HUDSON, P FANNIN, R BOULOM, K MCMILLIAN, MK POISNER, AM HONG, JS TI PROLONGED STIMULATION OF BOVINE ADRENAL CHROMAFFIN CELLS WITH ARACHIDONIC-ACID AND PROSTAGLANDIN-E2 INCREASES EXPRESSION OF THE PROENKEPHALIN GENE AND THE SECRETION OF [MET5]-ENKEPHALIN SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID A MESSENGER-RNA; PHENYLETHANOLAMINE N-METHYLTRANSFERASE; PHOSPHOINOSITIDE METABOLISM; CATECHOLAMINE RELEASE; MEDULLARY CELLS; ENKEPHALIN; ACTIVATION; BINDING; PHOSPHOLIPASE-A2; BIOSYNTHESIS AB The effects of long-term exposure of bovine adrenal medullary chromaffin (BAMC) cells to arachidonic acid (AA) and prostaglandin E2 (PGE2) on [Met5]-enkephalin (ME) secretion and expression of the proenkephalin A (proENK) gene were studied. Treatment with various concentrations of AA or PGE2 for 24 hr increased the secretion of ME in a concentration- and time-dependent manner. At high concentrations (10-100 muM), but not low (1-3 muM), AA significantly increased ME secretion by 1 hr. In contrast, the onset time for increase of ME secretion by PGE2 was 3 hr after exposure. The magnitude of increase in ME secretion in the presence of AA or PGE2 continued to increase with time. However, intracellular ME levels in AA- or PGE2-treated cells were not significantly different from that of controls, indicating that elevated levels of ME secretion into the media may be a result of increased biosynthesis of ME. In addition, AA or PGE2 increased proENK mRNA level in a concentration- and time-dependent manner. The onset time for the increase in proENK mRNA in response to PGE2 was 6 hr after exposure. The treatment of BAMC cells with 20 muM cycloheximide (a protein synthesis inhibitor) inhibited both the increased secretion of ME and proENK mRNA level induced by AA and PGE2 in a time-dependent manner, indicating that the delayed secretion of ME and the increase in proENK mRNA level induced by AA and PGE2 require protein synthesis. Indomethacin (a cyclooxygenase inhibitor, 10 muM) effectively inhibited AA-induced responses, whereas 10 muM nordihydroguaiaretic acid (a lipoxygenase inhibitor) was inactive. Thus, the responses induced by AA appeared to be mediated by a cyclooxygenase but not a lipoxygenase pathway. Taken together, our results indicate that AA and PGE2 may play important roles in the long-term regulation of ME secretion and expression of proENK mRNA in BAMC cells. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,NEUROPHARMACOL SECT,POB 12233,RES TRIANGLE PK,NC 27709. UNIV KANSAS,MED CTR,DEPT PHARMACOL,KANSAS CITY,KS 66103. NR 33 TC 10 Z9 10 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 NOV PY 1992 VL 263 IS 2 BP 527 EP 532 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JX704 UT WOS:A1992JX70400017 PM 1432687 ER PT J AU AULAKH, CS HILL, JL MURPHY, DL AF AULAKH, CS HILL, JL MURPHY, DL TI EFFECTS OF VARIOUS SEROTONIN RECEPTOR SUBTYPE-SELECTIVE ANTAGONISTS ALONE AND ON M-CHLOROPHENYLPIPERAZINE-INDUCED NEUROENDOCRINE CHANGES IN RATS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RADIOLIGAND BINDING; PROLACTIN SECRETION; RECOGNITION SITES; 5-HT3 RECEPTORS; BRAIN MEMBRANES; CORTICOSTERONE; STIMULATION; ACTIVATION; RESPONSES; PLASMA AB Administration of m-chlorophenylpiperazine [m-CPP, a serotonin (5-HT) agonist] to rats increases plasma concentrations of prolactin and corticosterone. Pretreatment with various doses of ritanserin (5-HT1C/5-HT2 antagonist), ICS 205-930 and MDL-72222 (5-HT3 antagonists), iodocyanopindolol or CG361A (beta adrenoceptor antagonists) and spiperone (5-HT1A/5-HT2 antagonist) did not attenuate m-CPP-induced increases in plasma concentrations of prolactin. In contrast, pretreatment with various doses of metergoline (5-HT1/5-HT2 antagonist), propranolol (beta adrenoceptor antagonist that also has binding affinity for 5-HT1A, 5-HT1B and 5-HT1C sites), mesulergine and mianserin (5-HT1C/5-HT2 antagonists) attenuated m-CPP-induced increases in plasma prolactin. On the other hand, m-CPP-induced increases in corticosterone concentrations were attenuated only by pretreatment with a low dose of mianserin and a high dose of spiperone. When administered without m-CPP, metergoline, mesulergine, ritanserin, ICS 205-930 and high doses of mianserin, spiperone and propranolol increased plasma corticosterone secretion. On the other hand, none of the antagonists used in the present study, except spiperone, had any significant effect on plasma prolactin secretion. These findings suggest that m-CPP-induced prolactin secretion is mediated by stimulation of 5-HT1C receptors while corticosterone secretion may be mediated either by an antagonistic effect at 5-HT3 receptor subtype or by non-serotonergic mechanisms. Alternatively, enhancement of corticosterone secretion by the 5-HT antagonists when administered alone may be responsible for their failure to block m-CPP-induced corticosterone secretion. Furthermore, enhancement of corticosterone secretion by the 5-HT antagonists in the present study may be due to their partial agonistic activity at 5-HT2 or 5-HT1A receptors or their effects on other neurotransmitter systems. RP AULAKH, CS (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,CLIN NEUROPHARMACOL SECT,10-3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 68 Z9 68 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 NOV PY 1992 VL 263 IS 2 BP 588 EP 595 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JX704 UT WOS:A1992JX70400025 PM 1432690 ER PT J AU CASH, JM CROFFORD, LJ GALLUCCI, WT STERNBERG, EM GOLD, PW CHROUSOS, GP WILDER, RL AF CASH, JM CROFFORD, LJ GALLUCCI, WT STERNBERG, EM GOLD, PW CHROUSOS, GP WILDER, RL TI PITUITARY-ADRENAL AXIS RESPONSIVENESS TO OVINE CORTICOTROPIN RELEASING HORMONE IN PATIENTS WITH RHEUMATOID-ARTHRITIS TREATED WITH LOW-DOSE PREDNISONE SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE RHEUMATOID ARTHRITIS; CORTICOTROPIN RELEASING HORMONE; ADRENOCORTICOTROPIC HORMONE; CORTISOL; PREDNISONE ID LEWIS RATS AB Ovine corticotropin-releasing hormone (oCRH) stimulation tests were performed in 8 female patients with active rheumatoid arthritis treated chronically with daily low dose prednisone and 16 age matched female controls. Patients were tested on the day of treatment, 12 h after their last prednisone dose, and after withholding prednisone for 36 h. Basal levels of plasma ACTH and to a lesser extent plasma cortisol levels were elevated before each test, and significant increases in ACTH and cortisol were induced with oCRH. The dose response relationship between total ACTH and total cortisol was shifted to the right, suggesting that the patient group had mildly deficient adrenocortical responsiveness compensated for by elevated basal evening ACTH concentrations. It is not known whether the neuroendocrine abnormalities demonstrated are due to an intrinsic preexisting abnormality, active disease, drug therapy or all these factors. C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RI Crofford, Leslie/J-8010-2013 NR 15 TC 65 Z9 65 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1992 VL 19 IS 11 BP 1692 EP 1696 PG 5 WC Rheumatology SC Rheumatology GA JY690 UT WOS:A1992JY69000009 PM 1337108 ER PT J AU YEH, CK FOX, PC GOTO, Y AUSTIN, HA BRAHIM, JS FOX, CH AF YEH, CK FOX, PC GOTO, Y AUSTIN, HA BRAHIM, JS FOX, CH TI HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) AND HIV INFECTED-CELLS IN SALIVA AND SALIVARY-GLANDS OF A PATIENT WITH SYSTEMIC LUPUS-ERYTHEMATOSUS SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE HIV; SALIVA; SALIVARY GLAND; SLE; PAROTID; ORAL ID TYPE-1 AB A young woman with systemic lupus erythematosus (SLE) was infected with human immunodeficiency virus 1 (HIV-1) and about 6 years later developed persistent bilateral parotid gland enlargement. It was unclear whether this represented salivary gland involvement as a component of her SLE (secondary Sjogren's syndrome) or the initial clinical manifestation of her HIV-1 infection. HIV proviral DNA was found in individual salivary glandular secretions and in whole saliva. Additionally, cells positive for HIV RNA were isolated from whole saliva. A parotid gland biopsy revealed infiltrating lymphocytes containing large amounts of HIV RNA. C1 NIH,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1N113,BETHESDA,MD 20892. NIDR,ORAL MED LAB,BETHESDA,MD 20892. NIDDK,KIDNEY DIS SECT,BETHESDA,MD. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 14 TC 21 Z9 21 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 1992 VL 19 IS 11 BP 1810 EP 1812 PG 3 WC Rheumatology SC Rheumatology GA JY690 UT WOS:A1992JY69000033 PM 1491408 ER PT J AU TAKAHASHI, N BREITMAN, TR AF TAKAHASHI, N BREITMAN, TR TI THE COVALENT LABELING OF PROTEINS BY 17-BETA-ESTRADIOL, RETINOIC ACID, AND PROGESTERONE IN THE HUMAN BREAST-CANCER CELL-LINES MCF-7 AND MCF-7/ADRR SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID CYCLIC-AMP; CARCINOMA-CELLS; MAMMARY-CANCER; 13-CIS-RETINOIC ACID; EMBRYONAL CARCINOMA; REGULATORY SUBUNITS; GROWTH-INVIVO; BINDING; INHIBITION; ESTRADIOL AB In this study we analyzed the covalent binding to proteins of 17beta-estradiol (E2), retinoic acid (RA), and progesterone in MCF-7 and MCF-7/Adr(R) cells. MCF-7 cells have receptors for E2 and progesterone. MCF-7/Adr(R) cells do not have these receptors. After a 1-day incubation period with either [H-3]E2, [H-3]progesterone, or [H-3]RA the levels of covalently bound radioactivity was between 1.4- to 2-fold greater in MCF-7 cells than in MCF-7/Adr(R) cells. We analyzed the labeled proteins with two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and fluorography. About 40 proteins were labeled by E2 in MCF-7 cells and about 10 of these proteins were the only proteins labeled by E2 in MCF-7/Adr(R) cells. We saw that the same 8 proteins were labeled by RA in both cell lines. Progesterone labeled 2 proteins with M(r) values of 37,000 and 20,000 in MCF-7 cells. These 2 proteins had mobilities that were the same as proteins that were labeled by either E2 or RA in both MCF-7 and MCF-7/Adr(R) cells. Besides these 2 proteins, we saw proteins of M(r) 51,000 (p51) and 55,000 that were covalently labeled by E2 in MCF-7 cells and by RA in both MCF-7 and MCF-7/Adr(R) cells. The p51 had the same mobility on 2D-PAGE as an 8-azido[ P-32]cAMP-labeled protein. This protein is probably RII(alpha), the type II cAMP-binding regulatory subunit of type II cAMP-dependent protein kinase. These results suggest that the estrogen receptor, while not obligatory, might still modulate the covalent linkage of E2 to protein. In addition, our results raise the possibility that some effects of some ligands of the thyroid/sterioid hormone receptor family may involve the covalent linking of these hormones to proteins, including RII(alpha). RP TAKAHASHI, N (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892, USA. NR 48 TC 15 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD NOV PY 1992 VL 43 IS 6 BP 489 EP 497 DI 10.1016/0960-0760(92)90235-B PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA JX499 UT WOS:A1992JX49900002 PM 1329924 ER PT J AU HIGUCHI, S PARRISH, KM DUFOUR, MC TOWLE, LH HARFORD, TC AF HIGUCHI, S PARRISH, KM DUFOUR, MC TOWLE, LH HARFORD, TC TI THE RELATIONSHIP BETWEEN 3 SUBTYPES OF THE FLUSHING RESPONSE AND DSM-III ALCOHOL-ABUSE IN JAPANESE SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID ETHNIC-DIFFERENCES; SENSITIVITY; DEFICIENCY AB This study examined the relationship between the flushing response and drinking patterns and DSM-III alcohol abuse among Japanese using data collected in the joint U.S.-Japan collaborative study. The flushing response was classified into the following three subtypes: typical flushing (always flushed in the face after drinking), atypical flushing (sometimes) and nonflushing (never). This study of male current drinkers showed that typical flushers drank less alcohol than did atypical and nonflushers, but there was no observed difference between the drinking patterns of atypical flushers and nonflushers. Although the relationship was less pronounced, a similar association was found for female current drinkers. The 12-month prevalence of DSM-III alcohol abuse was estimated to be highest among atypical flushers and lowest among typical flushers, with nonflushers in between for both genders. When daily alcohol consumption and other pertinent sociodemographic variables were controlled, logistic regression analyses revealed that the risk for alcohol abuse by men was approximately 3.0 times higher among atypical flushers and 1.7 times higher among nonflushers than among typical flushers. The corresponding risks for abuse by women were 7.8 (atypical flushers) and 2.8 (nonflushers) times higher. Possible explanations for these differences in drinking patterns and the risk for alcohol abuse among the three flushing subtypes and between genders are discussed. RP HIGUCHI, S (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 26 TC 12 Z9 12 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD NOV PY 1992 VL 53 IS 6 BP 553 EP 560 PG 8 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA JW454 UT WOS:A1992JW45400004 PM 1434631 ER PT J AU RETTEW, DC SWEDO, SE LEONARD, HL LENANE, MC RAPOPORT, JL AF RETTEW, DC SWEDO, SE LEONARD, HL LENANE, MC RAPOPORT, JL TI OBSESSIONS AND COMPULSIONS ACROSS TIME IN 79 CHILDREN AND ADOLESCENTS WITH OBSESSIVE-COMPULSIVE DISORDER SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE SYMPTOMS; OBSESSIVE-COMPULSIVE DISORDER; OBSESSIONS; COMPULSIONS ID CHILDHOOD; SYMPTOMS; CLOMIPRAMINE AB Individual symptoms of 79 children and adolescents with severe obsessive-compulsive disorder were obtained from chart review of at least two in-person evaluations and recorded across an average of 7.9 years (range, 2 to 16). Symptoms were grouped according to the categories of the Yale-Brown Symptom Checklist. No significant age related trends were found with any one type of symptom, although patients with a very early onset of illness (less than 6 years old) were more likely to have compulsions than obsessions. Across the study period, patients reported symptoms from many different symptom categories, with 47% of the patients displaying both washing and checking compulsions at some time during their illness. No patient maintained the same constellation of symptoms from presentation to follow-up. These data support the concept of obsessive-compulsive disorder as an illness with varied clinical manifestations that individually change over time. RP RETTEW, DC (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. NR 20 TC 108 Z9 108 U1 0 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1992 VL 31 IS 6 BP 1050 EP 1056 DI 10.1097/00004583-199211000-00009 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA JX700 UT WOS:A1992JX70000009 PM 1429404 ER PT J AU HORNSTEIN, NL PUTNAM, FW AF HORNSTEIN, NL PUTNAM, FW TI CLINICAL PHENOMENOLOGY OF CHILD AND ADOLESCENT DISSOCIATIVE DISORDERS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE DISSOCIATIVE DISORDER; CHILD ABUSE; SEXUAL ABUSE; PHYSICAL ABUSE; MULTIPLE PERSONALITY DISORDER ID MULTIPLE PERSONALITY-DISORDER; SYMPTOMS; ETIOLOGY; ABUSE AB A comparison of two separately diagnosed samples of children and adolescents with dissociative disorders demonstrates good construct validity for these diagnoses in childhood. Descriptive analyses of the total sample reveal a clinical profile characterized by a plethora of affective, anxiety, conduct, posttraumatic, and dissociative symptoms. Children with multiple personality disorder (MPD) differ from those with dissociative disorder not otherwise specified (DDNOS) in having more amnesias, identity disturbances, and hallucinations. Adolescents were more symptomatic than children age 11 or younger and more likely to receive a diagnosis of multiple personality disorder C1 NIMH,DEV PSYCHOL LAB,BETHESDA,MD 20892. RP HORNSTEIN, NL (reprint author), UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BEHAV SCI,UNIT DIRECTOR CHILDRENS INPATIENT UNIT 5W,LOS ANGELES,CA 90024, USA. NR 48 TC 89 Z9 89 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1992 VL 31 IS 6 BP 1077 EP 1085 DI 10.1097/00004583-199211000-00013 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA JX700 UT WOS:A1992JX70000013 PM 1429408 ER PT J AU BLACK, B UHDE, TW AF BLACK, B UHDE, TW TI ELECTIVE MUTISM AS A VARIANT OF SOCIAL PHOBIA SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ELECTIVE MUTISM; SOCIAL PHOBIA; FLUOXETINE ID CHILDREN; QUESTIONNAIRE; PHENELZINE; DISORDERS AB To examine the relationship between the syndromes of elective mutism and social phobia, a case of elective mutism associated with social phobia in a 12-year-old girl is presented, and the clinical literature regarding the syndrome of elective mutism is reviewed. Elective mutism or reluctance to speak in unfamiliar social situations may be a symptom of social phobia. Social anxiety is a nearly universal characteristic of children manifesting the syndrome of elective mutism. Elective mutism may respond to treatment with medications that also are effective in the treatment of social phobia. Elective mutism may be a manifestation of social phobia rather than a separate diagnostic syndrome. Pharmacologic treatment may be effective. C1 NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BLDG 10,BETHESDA,MD 20892. NR 33 TC 108 Z9 108 U1 6 U2 15 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1992 VL 31 IS 6 BP 1090 EP 1094 DI 10.1097/00004583-199211000-00015 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA JX700 UT WOS:A1992JX70000015 PM 1342579 ER PT J AU CEREMUZYNSKI, L KLECZAR, E KRZEMINSKAPAKULA, M KUCH, J NARTOWICZ, E SMIELAKKOROMBEL, J DYDUSZYNSKI, A MACIEJEWICZ, J ZALESKA, T LAZARCZYKKEDZIA, E MOTYKA, J PACZKOWSKA, B SCZANIECKA, O YUSUF, S AF CEREMUZYNSKI, L KLECZAR, E KRZEMINSKAPAKULA, M KUCH, J NARTOWICZ, E SMIELAKKOROMBEL, J DYDUSZYNSKI, A MACIEJEWICZ, J ZALESKA, T LAZARCZYKKEDZIA, E MOTYKA, J PACZKOWSKA, B SCZANIECKA, O YUSUF, S TI EFFECT OF AMIODARONE ON MORTALITY AFTER MYOCARDIAL-INFARCTION - A DOUBLE-BLIND, PLACEBO-CONTROLLED, PILOT-STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID REFRACTORY CARDIAC-ARRHYTHMIAS; LOW-DOSE AMIODARONE; VENTRICULAR ARRHYTHMIAS; CONTROLLED TRIAL; THERAPY; EFFICACY; PERSPECTIVE; TACHYCARDIA; TOXICITY; FAILURE AB Objectives. The goal of this study was to evaluate the effect of amiodarone on mortality, ventricular arrhythmias and clinical complications in high risk postinfarction patients. Background. No therapy has been shown to reduce sudden death in patients ineligible to receive beta-adrenergic blocking agents after myocardial infarction. Methods. Patients who were not eligible to receive beta-blockers were randomized to receive amiodarone (n = 305) or placebo (n = 308) for 1 year. Results. There were 21 deaths in the amiodarone group compared with 33 in the placebo group (odds ratio 0.62, 95% confidence interval [CI] 0.35 to 1.08, p = 0.095). There were two noncardiac deaths in the amiodarone group and none in the placebo group; thus, the difference in cardiac mortality (19 vs. 33, respectively) was statistically significant (odds ratio 0.55, 95% CI 0.32 to 0.", p = 0.048). There was a significant decrease in Lown class 4 ventricular arrhythmias (7.5% vs. 19.7%, respectively, p < 0.001). Adverse effects developed in 30% of amiodarone-treated patients and 10% of placebo-treated patients. Pulmonary toxicity, which was mild and reversible, occurred in only one patient in the amiodarone group but in no patient in the placebo group. Conclusions. This trial demonstrated a significant reduction in cardiac mortality and ventricular arrhythmias with amiodarone treatment. However, given the wide confidence intervals and borderline statistical significance of our trial, larger trials are needed to confirm or refute this view. C1 UNIV LODZ, LODZ, POLAND. EMERGENCY HOSP, WARSAW, POLAND. MED ACAD WARSAW, PL-02032 WARSAW, POLAND. CENT RAILWAY HOSP, WARSAW, POLAND. NHLBI, BETHESDA, MD 20892 USA. MED SCH BYDGOSZCZ, BYDGOSZCZ, POLAND. DIST HOSP, KRAKOW, POLAND. RP CEREMUZYNSKI, L (reprint author), POSTGRAD MED SCH, DEPT CARDIOL, SZPITAL GROCHOWSKI 04-073, GRENADIEROW 51-59, WARSAW, POLAND. NR 38 TC 258 Z9 261 U1 1 U2 4 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 NOV 1 PY 1992 VL 20 IS 5 BP 1056 EP 1062 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW465 UT WOS:A1992JW46500002 PM 1401602 ER PT J AU PANZA, JA DIODATI, JG CALLAHAN, TS EPSTEIN, SE QUYYUMI, AA AF PANZA, JA DIODATI, JG CALLAHAN, TS EPSTEIN, SE QUYYUMI, AA TI ROLE OF INCREASES IN HEART-RATE IN DETERMINING THE OCCURRENCE AND FREQUENCY OF MYOCARDIAL-ISCHEMIA DURING DAILY LIFE IN PATIENTS WITH STABLE CORONARY-ARTERY DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ANGINA-PECTORIS; NOCTURNAL ANGINA; AMBULATORY PATIENTS; CIRCADIAN VARIATION; EXERCISE; VARIABILITY; ANGIOPLASTY; SYMPTOMS; BURDEN; TONE AB Objectives. The goal of this study was to investigate the role of increases in heart rate in the development of ischemic episodes recorded during ambulatory electrocardiographic (ECG) monitoring in patients with stable coronary artery disease and to establish the importance of such increases in determining the frequency of ambulatory myocardial ischemia. Background. The factors that determine the occurrence and frequency of episodes of myocardial ischemia that patients with stable coronary artery disease experience during daily life have not been clearly defined. In particular, the role of increases in heart rate in the development of myocardial ischemia is controversial. Methods. To address these issues, 54 patients (42 men and 12 women, mean age 60.5 +/- 8 years) with proved coronary artery disease who had greater-than-or-equal-to 1 mm ST segment depresssion during exercise testing underwent an exercise treadmill test with use of the National Institutes of Health combined protocol and a 48-h period of ambulatory ECG monitoring. The exercise ischemic threshold was determined as the heart rate at the onset of ST segment depression during exercise testing. Results. During monitoring, 48 (89%) of the 54 patients had at least one episode of ST segment depression (mean +/- SD 6.6 +/- 5 episodes,, range 0 to 22). The majority (320 of 359 or 89%) of ischemic episodes were preceded by an increase in heart rate -10 beats/min; the most significant increase (22.3 +/- 10 beats/min) occurred during the 5-min period before the onset of the episode. An ischemic episode occurred 80% of the times the heart rate reached the exercise ischemic threshold. A strong correlation was observed between the number of times the exercise ischemic threshold was reached during monitoring and both the number and the duration of ischemic episodes (r = 0.90 and 0.71, respectively, p < 0.0001). Conclusions. Increases in heart rate that exceed the exercise ischemic threshold are commonly observed before the onset of episodes of ambulatory myocardial ischemia in patients with stable coronary artery disease. Moreover, such increases constitute an important determinant of the frequency of myocardial ischemia during daily life. These findings may explain the variability observed in the number of ischemic episodes and may have important implications for the mechanisms that contribute to myocardial ischemia in daily life and for the clinical evaluation of patients with coronary artery disease. RP PANZA, JA (reprint author), NHLBI,DIV CARDIOL,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 27 TC 55 Z9 58 U1 1 U2 2 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 NOV 1 PY 1992 VL 20 IS 5 BP 1092 EP 1098 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW465 UT WOS:A1992JW46500008 PM 1401608 ER PT J AU NEGGERS, Y GOLDENBERG, RL CLIVER, SP HOFFMAN, HJ CUTTER, GR AF NEGGERS, Y GOLDENBERG, RL CLIVER, SP HOFFMAN, HJ CUTTER, GR TI USEFULNESS OF VARIOUS MATERNAL SKINFOLD MEASUREMENTS FOR PREDICTING NEWBORN BIRTH-WEIGHT SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Note ID PREGNANCY; GROWTH; POPULATION; WOMEN C1 UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL 35233. UNIV ALABAMA,DEPT HUMAN NUTR,TUSCALOOSA,AL 35401. NICHHD,PREVENT RES PROGRAM,BETHESDA,MD 20892. FU NICHD NIH HHS [N01-HD-4-2811] NR 18 TC 10 Z9 10 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 1992 VL 92 IS 11 BP 1393 EP 1394 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JW631 UT WOS:A1992JW63100021 PM 1430729 ER PT J AU ENGELMAN, A CRAIGIE, R AF ENGELMAN, A CRAIGIE, R TI IDENTIFICATION OF CONSERVED AMINO-ACID-RESIDUES CRITICAL FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE FUNCTION-INVITRO SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; MOLECULAR CLONE; VIRAL-DNA; POL GENES; RETROVIRUS INTEGRATION; REVERSE-TRANSCRIPTASE; HUMAN SPUMARETROVIRUS; GENOME ORGANIZATION AB We have probed the structural organization of the human immunodeficiency virus type 1 integrase protein by limited proteolysis and the functional organization by site-directed mutagenesis of selected amino acid residues. A central region of the protein was relatively resistant to proteolysis. Proteins with altered amino acids in this region, or in the N-terminal part of the protein that includes a putative zinc-binding motif, were purified and assayed for 3' processing, DNA strand transfer, and disintegration activities in vitro. In general, these mutations had parallel effects on 3' processing and DNA strand transfer, suggesting that integrase may utilize a single active site for both reactions. The only proteins that were completely inactive in all three assays contained mutations at conserved amino acids in the central region, suggesting that this part of the protein may be involved in catalysis. In contrast, none of the mutations in the N-terminal region resulted in a protein that was inactive in all three assays, suggesting that this part of integrase may not be essential for catalysis. The disintegration reaction was particularly insensitive to these amino acid substitutions, indicating that some function that is important for 3' processing and DNA strand transfer may be dispensable for disintegration. C1 NIDDK, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 61 TC 428 Z9 434 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 1992 VL 66 IS 11 BP 6361 EP 6369 PG 9 WC Virology SC Virology GA JT700 UT WOS:A1992JT70000014 PM 1404595 ER PT J AU ZHANG, YF KECK, JG MOSS, B AF ZHANG, YF KECK, JG MOSS, B TI TRANSCRIPTION OF VIRAL LATE GENES IS DEPENDENT ON EXPRESSION OF THE VIRAL INTERMEDIATE GENE G8R IN CELLS INFECTED WITH AN INDUCIBLE CONDITIONAL-LETHAL MUTANT VACCINIA VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; DNA-POLYMERASE GENE; RNA-POLYMERASE; MESSENGER-RNA; LAC REPRESSOR; PHENOTYPIC CHARACTERIZATION; 147-KILODALTON SUBUNITS; ESCHERICHIA-COLI; CAPPING ENZYME; SYSTEM AB There are three temporal classes of vaccinia virus genes: early, intermediate, and late. The object of this study was to determine the effects on virus replication of regulating the expression of G8R, an intermediate gene that encodes a late transcription factor. We inserted the lac operator adjacent to the RNA start site of the G8R gene in a recombinant vaccinia virus that constitutively expresses the Escherichia coli lac repressor to make expression of the G8R gene dependent on the inducer isopropyl-beta-D-thiogalactopyranoside (IPTG). In case repression would not be complete, we also weakened the promoter of the G8R gene by making a single-nucleotide substitution designed to reduce its basal level of transcription. The mutant virus replicated well in the presence of the inducer, although synthesis of the G8R-encoded 30,000-M(r) protein was only 10% of that of the wild-type virus. In the absence of IPTG, (i) synthesis of the G8R protein was inhibited by more than 99% relative to that of the wild-type virus, (ii) synthesis of early and intermediate mRNAs appeared to be unaffected, (iii) intermediate proteins accumulated to higher than normal levels, (iv) synthesis of late mRNA and protein was reduced by about 90%, (v) viral DNA was replicated but incompletely resolved concatemeric molecules accumulated, (vi) not even the earliest stages of virion assembly were detectable by transmission electron microscopy, and (vii) virus yield under one-step growth conditions and plaque formation were 10(-3) and 10(-4) times the wild-type values, respectively. The defect in late gene expression could be overcome by transfection of a G8R gene that was not under lac operator control, as well as by addition of IPTG, further demonstrating the specificity of the repression. The correlation between decreased expression of the G8R intermediate gene and inhibition of late mRNA synthesis is consistent with the notion that the G8R product serves as an essential late transcription factor and supports a cascade mechanism of vaccinia virus gene regulation. In addition, the inducer-dependent vaccinia virus mutant provided a tool for selective inhibition of late gene expression while allowing synthesis of early and intermediate mRNAs and proteins. C1 NIAID,VIRAL DIS LAB,BLDG 4,ROOM 229,BETHESDA,MD 20892. NR 62 TC 35 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1992 VL 66 IS 11 BP 6470 EP 6479 PG 10 WC Virology SC Virology GA JT700 UT WOS:A1992JT70000025 PM 1404599 ER PT J AU CHESEBRO, B WEHRLY, K NISHIO, J PERRYMAN, S AF CHESEBRO, B WEHRLY, K NISHIO, J PERRYMAN, S TI MACROPHAGE-TROPIC HUMAN-IMMUNODEFICIENCY-VIRUS ISOLATES FROM DIFFERENT PATIENTS EXHIBIT UNUSUAL V3 ENVELOPE SEQUENCE HOMOGENEITY IN COMPARISON WITH T-CELL-TROPIC ISOLATES - DEFINITION OF CRITICAL AMINO-ACIDS INVOLVED IN CELL TROPISM SO JOURNAL OF VIROLOGY LA English DT Article ID PRINCIPAL NEUTRALIZING DETERMINANT; CENTRAL NERVOUS-SYSTEM; MONONUCLEAR PHAGOCYTES; AIDS PATIENTS; HTLV-III; INFECTION; TYPE-1; HIV-1; IDENTIFICATION; GP120 AB Previous experiments indicate that the V3 hypervariable region of the human immunodeficiency virus (HIV) envelope protein influences cell tropism of infection; however, so far no consistent V3 sequence can account for macrophage or T-cell tropism. In these experiments, we studied infectious recombinant HIV clones constructed by using V3 region sequences of HIV isolates from 16 patients to search for sequences associated with cell tropism. Remarkable homology was seen among V3 sequences from macrophage-tropic clones from different patients, and a consensus V3 region sequence for patient-derived macrophage-tropic viruses was identified. In contrast, V3 sequences of T-cell-tropic clones from different patients were highly heterogeneous, and the results suggested that sequence diversity leading to T-cell tropism might be generated independently in each patient. Site-specific mutations identified amino acids at several positions on each side of the GPGR motif at the tip of the V3 loop as important determinants of tropism for T cells and macrophages. However, a wide variety of mutant V3 sequences induced macrophage tropism, as detected in vitro. Therefore, the homogeneity of macrophage-tropic patient isolates appeared to be the result of selection based on a biological advantage in vivo. RP CHESEBRO, B (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 34 TC 510 Z9 513 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1992 VL 66 IS 11 BP 6547 EP 6554 PG 8 WC Virology SC Virology GA JT700 UT WOS:A1992JT70000035 PM 1404602 ER PT J AU EMERSON, SU LEWIS, M GOVINDARAJAN, S SHAPIRO, M MOSKAL, T PURCELL, RH AF EMERSON, SU LEWIS, M GOVINDARAJAN, S SHAPIRO, M MOSKAL, T PURCELL, RH TI CDNA CLONE OF HEPATITIS-A VIRUS ENCODING A VIRULENT VIRUS - INDUCTION OF VIRAL-HEPATITIS BY DIRECT NUCLEIC-ACID TRANSFECTION OF MARMOSETS SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; CELL-CULTURE; WILD-TYPE; IDENTIFICATION; ATTENUATION; ADAPTATION; STRAINS; PASSAGE; GENOME AB Direct inoculation of marmoset livers with an in vitro transcription mixture containing cDNA and full-length genomic RNA transcripts of hepatitis A virus resulted in acute viral hepatitis. Elevations in serum levels of liver enzymes were correlated with appearance of antibody to hepatitis A virus. Genomes of infectious hepatitis A virus isolated from the feces of transfected marmosets contained the same mutation as the cDNA template used for transfection. Liver biopsies confirmed that the virus encoded by the cDNA clone induced histopathological changes equivalent to those caused by virulent wild-type virus. C1 RANCHO LOS AMIGOS MED CTR,PATHOL & CLIN LABS,DOWNEY,CA 90242. BIOQUAL INC,ROCKVILLE,MD 20853. RP EMERSON, SU (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 23 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1992 VL 66 IS 11 BP 6649 EP 6654 PG 6 WC Virology SC Virology GA JT700 UT WOS:A1992JT70000047 PM 1328684 ER PT J AU CHEUNG, SC DIETZSCHOLD, B KOPROWSKI, H NOTKINS, AL RANDO, RF AF CHEUNG, SC DIETZSCHOLD, B KOPROWSKI, H NOTKINS, AL RANDO, RF TI A RECOMBINANT HUMAN FAB EXPRESSED IN ESCHERICHIA-COLI NEUTRALIZES RABIES VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; TUMOR-LOCALIZATION; GLYCOPROTEIN; FRAGMENTS; LAMBDA; CELLS; DETERMINANT; INHIBITION; ATTACHMENT; GENERATION AB A recombinant human anti-rabies monoclonal antibody (MAb-57) Fab was prepared by cloning the heavy (Fd)- and light-chain domains into the same bacterial expression vector. To construct the recombinant Fab, mRNA was extracted from MAb-57-producing hybridoma cells, reverse transcribed, and then amplified by polymerase chain reaction (PCR) by using oligonucleotides specific for immunoglobulin heavy- and light-chain DNA sequences. PCR-amplified Fd-chain cDNA was fused, in frame, between a bacterial leader peptide (PelB) at the amino terminus and a 10-amino-acid peptide tag at the carboxy terminus. The PCR-amplified lambda-chain cDNA was also fused to the PelB leader peptide. The immunoglobulin Fab was then expressed as a dicistronic message in bacteria by using the isopropyl-beta-D-thiogalactopyranoside-inducible lactose promotor (lacZ). DNA sequencing was used to define the gamma-chain isotype (immunoglobulin G1) and V(H) (V(H)I) chain and V(L) (VlambdaII) chain gene usage. The recombinant Fab (rFab57) specifically bound the rabies virus cost glycoprotein, while the Fd and lambda chains, when expressed individually, did not. The binding specificity of rFab57 was indistinguishable from that of the intact MAb in direct enzyme-linked immunosorbent assays; however, the dissociation constant of rFab57 for rabies virus protein G was approximately 1 log10 U lower than that of complete MAb-57 in competition enzyme-linked immunosorbent assays. A fluorescent-focus inhibition assay showed that bacterially expressed rFab was capable of neutralizing rabies virus strain CVS-11. We conclude that a human Fab expressed in bacteria maintains its specificity and biologic activity. C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. NR 42 TC 31 Z9 34 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1992 VL 66 IS 11 BP 6714 EP 6720 PG 7 WC Virology SC Virology GA JT700 UT WOS:A1992JT70000053 PM 1404611 ER PT J AU CHENG, SM LEE, SG RONCHETTIBLUME, M VIRK, KP MIZUTANI, S EICHBERG, JW DAVIS, A HUNG, PP HIRSCH, VM CHANOCK, RM PURCELL, RH JOHNSON, PR AF CHENG, SM LEE, SG RONCHETTIBLUME, M VIRK, KP MIZUTANI, S EICHBERG, JW DAVIS, A HUNG, PP HIRSCH, VM CHANOCK, RM PURCELL, RH JOHNSON, PR TI COEXPRESSION OF THE SIMIAN IMMUNODEFICIENCY VIRUS ENV AND REV PROTEINS BY A RECOMBINANT HUMAN ADENOVIRUS HOST RANGE MUTANT SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL MESSENGER-RNA; SV40 T-ANTIGEN; PRODUCTIVE INFECTION; SURFACE-ANTIGEN; TRANS-ACTIVATOR; TARGET SEQUENCE; LATE PROMOTER; SIV REV; EXPRESSION; BINDING AB Recombinant human adenoviruses (Ads) that replicate in the intestinal tract offer a novel, yet practical, means of immunoprophylaxis against a wide variety of viral and bacterial pathogens. For some infectious agents such as human immunodeficiency vims (HIV), the potential for residual infectious material in vaccine preparations must be eliminated. Therefore, recombinant human Ads that express noninfectious HIV or other microbial proteins are attractive vaccine candidates. To test such an approach for HIV, we chose an experimental model of AIDS based on simian immunodeficiency virus (SIV) infection of macaques. Our data demonstrate that the SIV Env gene products are expressed in cultured cells after infection with a recombinant Ad containing both SIV env and rev genes. An E3 deletion vector derived from a mutant of human Ad serotype 5 that efficiently replicates in both human and monkey cells was used to bypass the usual host range restriction of Ad infection. In addition, we show that the SIV rev gene is properly spliced from a single SIV subgenomic DNA fragment and that the Rev protein is expressed in recombinant Ad-SIV-infected human as well as monkey cells. The expression of SIV gene products in suitable live Ad vectors provides an excellent system for studying the regulation of SIV gene expression in cultured cells and evaluating the immunogenicity and protective efficacy of SIV proteins in macaques. C1 GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,RETROVIRAL PATHOGENESIS SECT,ROCKVILLE,MD 20852. NIH,INFECT DIS LAB,BETHESDA,MD 20892. RP CHENG, SM (reprint author), WYETH AYERST RES,DIV BIOTECHNOL & MICROBIOL,POB 8299,PHILADELPHIA,PA 19101, USA. RI Johnson, Philip/A-6892-2009 FU NIAID NIH HHS [N01-AI-72623] NR 31 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1992 VL 66 IS 11 BP 6721 EP 6727 PG 7 WC Virology SC Virology GA JT700 UT WOS:A1992JT70000054 PM 1404612 ER PT J AU BARKER, CS BEAR, SE KELER, T COPELAND, NG GILBERT, DJ JENKINS, NA YEUNG, RS TSICHLIS, PN AF BARKER, CS BEAR, SE KELER, T COPELAND, NG GILBERT, DJ JENKINS, NA YEUNG, RS TSICHLIS, PN TI ACTIVATION OF THE PROLACTIN RECEPTOR GENE BY PROMOTER INSERTION IN A MOLONEY MURINE LEUKEMIA VIRUS-INDUCED RAT THYMOMA SO JOURNAL OF VIROLOGY LA English DT Article ID GROWTH-HORMONE; ERYTHROPOIETIN RECEPTOR; IL-2 RECEPTOR; LYMPHOCYTES-T; BETA-CHAIN; INTERLEUKIN-2; FAMILY; LYMPHOMAS; BINDING; CLONING AB The prolactin receptor (Prlr) and growth hormone receptor (Ghr) genes and the Moloney murine leukemia virus integration-2 (Mlvi-2) locus were mapped to mouse chromosome 15 and human chromosome 5 bands p12-p14. To examine the potential relationship between Mlvi-2 and the genes encoding the growth hormone receptor and the prolactin receptor, we determined the chromosomal location of all three loci in the rat, using a panel of rat-mouse somatic cell hybrids, and in the mouse, using a panel of (C57BL/6J x Mus spretus)F1 x C57BL/6J interspecific backcross mice. These analyses revealed that Ghr, Prlr, and Mlvi-2 map to chromosome 2 in the rat and to chromosome 15 in the mouse, in close proximity with each other. Pulsed-field gel electrophoresis of rat genomic DNA showed no overlaps between the gene encoding the prolactin receptor and the remaining loci. Moreover, expression of the prolactin receptor was not affected by provirus insertion in Mlvi-2. During these studies, however, we detected one T-cell lymphoma line (2779) in which the prolactin receptor gene was activated by provirus integration. Sequence analysis of polymerase chain reaction-derived cDNA clones showed that the prolactin receptor RNA message initiates at the 5' long terminal repeat and utilizes the splice donor site 5' of the gag gene to splice the viral sequences onto exon 1 of the prolactin receptor. This message is predicted to encode the intact prolactin receptor protein product. Exposure of the T-cell lymphoma line 2779 to prolactin promoted cellular proliferation. C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ABL,FREDERICK,MD 21702. FU NCI NIH HHS [CA-06927, CA-38047]; NCRR NIH HHS [RR-05539] NR 39 TC 25 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1992 VL 66 IS 11 BP 6763 EP 6768 PG 6 WC Virology SC Virology GA JT700 UT WOS:A1992JT70000059 PM 1404614 ER PT J AU KOTLER, M ARAD, G HUGHES, SH AF KOTLER, M ARAD, G HUGHES, SH TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GAG-PROTEASE FUSION PROTEINS ARE ENZYMATICALLY ACTIVE SO JOURNAL OF VIROLOGY LA English DT Note ID MURINE LEUKEMIA-VIRUS; ESCHERICHIA-COLI; RETROVIRAL PROTEASE; ASPARTIC PROTEASE; HTLV-III; EXPRESSION; SEQUENCE; PEPTIDE; HIV-1; FORM AB We have introduced mutations into the region of the genome of human immunodeficiency virus type 1 (HIV-1) that encodes the cleavage sites between the viral protease (PR) and the adjacent upstream region of the polyprotein precursor. Segments containing these mutations were introduced into plasmids, and the retroviral proteins were expressed in Escherichia coli. The mutations prevented cleavage between the PR and the adjacent polypeptide; however, other PR cleavage sites in the polyprotein were cleaved normally, showing that the release of free PR is not a prerequisite for the appropriate processing of HIV-1 precursors. C1 NCI, FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ABL, POB B, FREDERICK, MD 21702 USA. HEBREW UNIV JERUSALEM, HADASSAH MED SCH, DEPT MOLEC GENET, IL-91010 JERUSALEM, ISRAEL. FU NCI NIH HHS [N01-CO-74101] NR 24 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 1992 VL 66 IS 11 BP 6781 EP 6783 PG 3 WC Virology SC Virology GA JT700 UT WOS:A1992JT70000063 PM 1404618 ER PT J AU COSTANZA, ME ANNAS, GJ BROWN, ML CASSEL, CK CHAMPION, V COHEN, HJ FRAME, PS GLASSE, L MOR, V PAUKER, SG AF COSTANZA, ME ANNAS, GJ BROWN, ML CASSEL, CK CHAMPION, V COHEN, HJ FRAME, PS GLASSE, L MOR, V PAUKER, SG TI SUPPORTING STATEMENTS AND RATIONALE SO JOURNALS OF GERONTOLOGY LA English DT Article ID BREAST SELF-EXAMINATION; CANCER MORTALITY; SCREENING MAMMOGRAPHY; RISING INCIDENCE; LOW-COST; HEALTH; PROJECT; OLDER; RISK; AGE C1 BOSTON UNIV,SCH MED,BOSTON,MA 02118. NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,BETHESDA,MD 20892. UNIV CHICAGO,SCH MED,GEN INTERNAL MED SECT,CHICAGO,IL 60637. INDIANA UNIV,SCH NURSING,INDIANAPOLIS,IN 46204. DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. TRI CTY MED ASSOCIAT,COHOCTON,NY. OLDER WOMENS LEAGUE,POUGHKEEPSIE,NY. BROWN UNIV,CTR GERONTOL & HLTH CARE,PROVIDENCE,RI 02912. NEW ENGLAND MED CTR,DIV CLIN DECIS MAKING,BOSTON,MA 02111. RP COSTANZA, ME (reprint author), UNIV MASSACHUSETTS,SCH MED,WORCESTER,MA 01605, USA. NR 92 TC 12 Z9 12 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1992 VL 47 SI SI BP 7 EP 16 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA KA426 UT WOS:A1992KA42600004 PM 1430887 ER PT J AU BROWN, ML AF BROWN, ML TI ECONOMIC-CONSIDERATIONS IN BREAST-CANCER SCREENING OF OLDER WOMEN SO JOURNALS OF GERONTOLOGY LA English DT Article ID COST-EFFECTIVENESS; MAMMOGRAPHY; PROGRAM AB The incidence of breast cancer increases with age, tending to result in more favorable cost-effectiveness outcomes with more advanced age of the screened population. On the other hand, the decreased remaining life expectancy of older women can be expected to reduce the cost effectiveness of screening. To assess these competing factors, the cost effectiveness of a long-term breast cancer screening program was evaluating using a computerized simulation model. The cost per life year saved decreased when the 65-69 year age group was added to a program screening women aged 50-64. For older age groups, however, cost effectiveness became relatively less favorable. The cost per life year saved of screening the 80-84 year age group was 55% higher than for the 65-69 group. RP BROWN, ML (reprint author), NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,SURVEILLANCE PROGRAM,BETHESDA,MD 20892, USA. NR 38 TC 36 Z9 36 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1992 VL 47 SI SI BP 51 EP 58 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA KA426 UT WOS:A1992KA42600009 PM 1430883 ER PT J AU CAPLAN, LS WELLS, BL HAYNES, S AF CAPLAN, LS WELLS, BL HAYNES, S TI BREAST-CANCER SCREENING AMONG OLDER RACIAL ETHNIC-MINORITIES AND WHITES - BARRIERS TO EARLY DETECTION SO JOURNALS OF GERONTOLOGY LA English DT Article ID MEDICAL-CARE; BLACK-WOMEN; STAGE; AGE; MAMMOGRAPHY; DIAGNOSIS AB Screening mammography for early detection of breast cancer has been shown to be an effective method for reducing mortality in older women. Based on the results from the 1987-88 National Health Interview Survey, older minority women have low prevalence rates of screening mammography. Among women aged 75 and older, 83.5% of Black women, 93.2% of Hispanic women, and 75.0% of White women have never had a mammogram. On the average, about 12% of minority women over the age of 65 have had a screening mammogram within the preceding year, compared with about 15% of White women. Among women 75+ years of age, Black and Hispanic women had markedly lower rates of clinical breast examination in the last year (23.4% and 20.5% respectively) as compared to White women (35.2%). The most common reason for not having a mammogram among Black women 65 years of age and older was that the doctor did not recommend a mammogram. For Hispanic and White women in this age group, the most common reason was that a mammogram was not needed or not necessary. Aggressive and creative breast cancer screening activities for minority women aged 65 and older are clearly indicated. C1 NCI,DIV CANC PREVENT & CONTROL,CANC CONTROL SCI PROGRAM,EPN ROOM 218,BETHESDA,MD 20892. NR 30 TC 152 Z9 153 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1992 VL 47 SI SI BP 101 EP 110 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA KA426 UT WOS:A1992KA42600017 PM 1430871 ER PT J AU CARRARO, R LI, ZH JOHNSON, JE GREGERMAN, RI AF CARRARO, R LI, ZH JOHNSON, JE GREGERMAN, RI TI ADIPOCYTES OF OLD RATS PRODUCE A DECREASED AMOUNT OF DIFFERENTIATION FACTOR FOR PREADIPOCYTES DERIVED FROM ADIPOSE-TISSUE ISLETS SO JOURNALS OF GERONTOLOGY LA English DT Article ID FAT-CELLS; WOMEN; METABOLISM; CULTURES; ADIPSIN; OBESITY AB Adipose tissue of young rats (3.5 mo) contains cell formations ("islets") that, in culture, give rise to a variety of preadipocytes, or islet-derived cells (IDCs), that undergo rapid morphologic differentiation into adipocytes. Such adipose conversion depends on a differentiation-promoting factor produced by the mature adipocytes also present in the cultures. Here we report that cultured IDCs from epididymal fat of senescent rats (20 +/- 3 mo) show decreased adipose conversion compared to IDCs from 3.5 mo rats at 3 days of culture (14.2% vs 29.9%; p < .001). Both the number of co-cultured adipocytes and increased fragility with age were excluded as having a substantial role in explaining the decreased conversion. In order to determine whether the decreased differentiation of the IDCs of the old rats was intrinsic or due to reduced production of the differentiation factor by the old adipocytes, cross-over cultures of IDCs from young and old rats were grown in the presence of young or old adipocytes. When IDCs of old rats were cultured in the presence of young adipocytes, a significant twofold increase in differentiation was seen compared to old IDCs grown with old adipocytes (22.7% vs 10.3%; p < .001). This response was comparable to that of young IDCs grown with young adipocytes. Thus, old IDCs retain their ability to undergo extensive morphologic differentiation when appropriately stimulated. Reduced production of the differentiation-promoting factor by old adipocytes rather than the ability of IDCs to differentiate appears to be responsible for the decreased adipose conversion of IDCs seen in cultures of adipose tissue from senescent rats. C1 UNIV PADUA,DEPT INTERNAL MED,I-35100 PADUA,ITALY. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. SRI INT,DEPT NEUROSCI,MENLO PK,CA 94025. LOEB RES INST,OTTAWA,ONTARIO,CANADA. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NR 17 TC 4 Z9 4 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1992 VL 47 IS 6 BP B198 EP B201 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA JX157 UT WOS:A1992JX15700017 PM 1430848 ER PT J AU WARNER, HR CAMPISI, J CRISTOFALO, VJ MILLER, RA PAPACONSTANTINOU, J PEREIRASMITH, O SMITH, JR WANG, E AF WARNER, HR CAMPISI, J CRISTOFALO, VJ MILLER, RA PAPACONSTANTINOU, J PEREIRASMITH, O SMITH, JR WANG, E TI CONTROL OF CELL-PROLIFERATION IN SENESCENT CELLS SO JOURNALS OF GERONTOLOGY LA English DT Editorial Material C1 LAWRENCE BERKELEY LAB,BERKELEY,CA 94720. MED COLL PENN,PHILADELPHIA,PA 19129. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. BAYLOR COLL MED,HOUSTON,TX 77030. LADY DAVIS INST MED RES,MONTREAL,QUEBEC,CANADA. RP WARNER, HR (reprint author), NIA,BETHESDA,MD 20892, USA. RI Papaconstantinou, John/E-3312-2010 NR 0 TC 6 Z9 6 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1992 VL 47 IS 6 BP B185 EP B189 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA JX157 UT WOS:A1992JX15700015 PM 1430846 ER PT J AU HAYNES, SG ORY, MG AF HAYNES, SG ORY, MG TI SCREENING FOR BREAST-CANCER IN OLDER WOMEN - THE MISSED COHORT - PREFACE SO JOURNALS OF GERONTOLOGY LA English DT Editorial Material RP HAYNES, SG (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1992 VL 47 SI SI BP R7 EP R8 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA KA426 UT WOS:A1992KA42600001 ER PT J AU SANDLER, DP AF SANDLER, DP TI EPIDEMIOLOGY AND ETIOLOGY OF ACUTE-LEUKEMIA - AN UPDATE SO LEUKEMIA LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL COURSE - LEUKEMIA 1992 : RECENT PROGRESS IN BIOLOGY AND CLINICAL RESEARCH IN ADULT LEUKEMIA CY JUL 04-07, 1992 CL GENOA, ITALY ID UNITED-STATES; CIGARETTE-SMOKING; MORTALITY PATTERNS; CANCER MORTALITY; ADULT LEUKEMIA; WORKERS; RISK; HAMPSHIRE; BENZENE RP SANDLER, DP (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. OI Sandler, Dale/0000-0002-6776-0018 NR 35 TC 13 Z9 13 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 1992 VL 6 SU 4 BP 3 EP 5 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA KA432 UT WOS:A1992KA43200002 PM 1434828 ER PT J AU LEVINE, PH ABLASHI, DV SAXINGER, WC CONNELLY, RR AF LEVINE, PH ABLASHI, DV SAXINGER, WC CONNELLY, RR TI ANTIBODIES TO HUMAN HERPES VIRUS-6 IN PATIENTS WITH ACUTE LYMPHOCYTIC-LEUKEMIA SO LEUKEMIA LA English DT Note ID HUMAN HERPESVIRUS-6 HHV-6; EPSTEIN-BARR-VIRUS; LYMPHOMA; IDENTIFICATION; PREVALENCE; SEQUENCES; HBLV; AGE AB Human herpesvirus-6 (HHV-6), a ubiquitous virus that causes exanthem subitum and occasional cases of infectious mononucleosis, hepatitis and other viral syndromes, has also been associated with acute lymphocytic leukemia (ALL) in children. To further investigate this association, we obtained sera from 50 patients with ALL and 50 age-sex matched controls. Antibodies to HHV-6 were determined using ELISA and indirect immunofluorescent antibody (IFA) tests. No significant difference between antibody titers in the cases and controls was observed. Since seroepidemiologic studies have demonstrated higher HHV-6 antibody titers in young children than in adults, this serologic study suggests that the previous association reported for HHV-6 and ALL was a result of the age of the population rather than a relationship between the virus and the disease. RP LEVINE, PH (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 434,BETHESDA,MD 20892, USA. NR 24 TC 17 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 1992 VL 6 IS 11 BP 1229 EP 1231 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA JZ293 UT WOS:A1992JZ29300024 PM 1331626 ER PT J AU RIPAMONTI, U MA, S CUNNINGHAM, NS YEATES, L REDDI, AH AF RIPAMONTI, U MA, S CUNNINGHAM, NS YEATES, L REDDI, AH TI INITIATION OF BONE REGENERATION IN ADULT BABOONS BY OSTEOGENIN, A BONE MORPHOGENETIC PROTEIN SO MATRIX LA English DT Article DE BONE INDUCTION; BONE MORPHOGENETIC PROTEINS; COLLAGENOUS MATRIX; OSTEOGENIN; PRIMATES ID GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; EMBRYONIC-DEVELOPMENT; INDUCTIVE PROTEIN; DIFFERENTIATION; BOVINE; GENE; LOCALIZATION; PURIFICATION; SUPERFAMILY AB Osteogenin, and related bone morphogenetic proteins, induce endochondral bone differentiation through a cascade of events which include formation of cartilage, hypertrophy and calcification of the cartilage, vascular invasion, differentiation of osteoblasts, and formation of bone. These events have been studied in a postnatal model of bone development in rodents. Information concerning the morphogenetic potential of osteogenin in primates is a prerequisite for potential clinical application in man. The efficacy of allogeneic osteogenin in primates was investigated in both extraskeletal and skeletal sites in 19-Chacma baboons (Papio ursinus). Osteogenin was isolated from demineralized baboon bone matrix and purified by chromatography on heparin-Sepharose, hydroxyapatite, and Sephacryl S-200. Protein fractions with a molecular mass range of 26-42 kDa induced cartilage and bone differentiation in the subcutaneous space of rats. Final purification to homogeneity was obtained by electroendosmotic elution from a preparative sodium dodecyl sulphate (SDS) polyacrylamide gel, resulting in a single band on a SDS-polyacrylamide gel with an apparent molecular mass of 30-34 kDa, with biological activity in rats. The osteoinductive potential of osteogenin in primates was tested first in intramuscular sites in baboons and found to be active. The bone regeneration potential was investigated in nonhealing calvarial defects surgically prepared in adult male baboons. Baboon osteogenin induced complete regeneration of the cranial wound. These findings in adult primates establish a primary role for osteogenin in initiation and promotion of osteogenesis, and imply a potential therapeutic application based on cell biology of extracellular matrix-cell interactions. C1 UNIV WITWATERSRAND,DENT RES INST,MRC,JOHANNESBURG 2001,SOUTH AFRICA. NIH,BONE CELL BIOL SECT,BETHESDA,MD 20892. UNIV WITWATERSRAND,DEPT BIOCHEM,JOHANNESBURG 2001,SOUTH AFRICA. RI Roden, Laura/D-1364-2010 OI Roden, Laura/0000-0002-1941-898X NR 39 TC 81 Z9 82 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0934-8832 J9 MATRIX JI Matrix PD NOV PY 1992 VL 12 IS 5 BP 369 EP 380 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA068 UT WOS:A1992KA06800004 PM 1484504 ER PT J AU HARA, H ABBOTT, WGH PATTI, L RUOTOLO, G SWINBURN, BA FIELDS, RM KATAOKA, S HOWARD, BV AF HARA, H ABBOTT, WGH PATTI, L RUOTOLO, G SWINBURN, BA FIELDS, RM KATAOKA, S HOWARD, BV TI INCREASED RECEPTOR-BINDING OF LOW-DENSITY-LIPOPROTEIN FROM INDIVIDUALS CONSUMING A HIGH-CARBOHYDRATE, LOW SATURATED-FAT DIET SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID KINETIC HETEROGENEITY; MEDIATED ENDOCYTOSIS; CHEMICAL-COMPOSITION; HUMAN-FIBROBLASTS; LDL RECEPTOR; METABOLISM; CELLS; HYPERCHOLESTEROLEMIA; APOLIPOPROTEIN-B-100; INTERNALIZATION C1 MEDLANT RES INST,GEORGE HYMAN MEM RES BLDG,ROOM 242,108 IRVING ST NW,WASHINGTON,DC 20010. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ. NR 48 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 1992 VL 41 IS 11 BP 1154 EP 1160 DI 10.1016/0026-0495(92)90002-R PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JZ273 UT WOS:A1992JZ27300002 PM 1435284 ER PT J AU VANBEMMEL, JH MCCRAY, AT AF VANBEMMEL, JH MCCRAY, AT TI ADVANCES IN AN INTERDISCIPLINARY SCIENCE SO METHODS OF INFORMATION IN MEDICINE LA English DT Article ID PROBLEM DECOMPOSITION METHOD; RECORD LINKAGE STRATEGIES; MEDICAL DECISION-MAKING; NEURAL NETWORK; DIAGNOSTIC PERFORMANCE; EFFICIENT DIAGNOSIS; 3-D RECONSTRUCTION; MULTIPLE DISORDERS; EXPERT SYSTEMS; HEART-DISEASE C1 NATL LIB MED,BETHESDA,MD 20894. RP VANBEMMEL, JH (reprint author), ERASMUS UNIV,FAC MED & HLTH SCI,DEPT MED INFORMAT,POB 1738,3000 DR ROTTERDAM,NETHERLANDS. NR 75 TC 1 Z9 1 U1 1 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD NOV PY 1992 VL 31 IS 4 BP 235 EP 246 PG 12 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA KC346 UT WOS:A1992KC34600003 PM 1470034 ER PT J AU KONKEL, ME HAYES, SF JOENS, LA CIEPLAK, W AF KONKEL, ME HAYES, SF JOENS, LA CIEPLAK, W TI CHARACTERISTICS OF THE INTERNALIZATION AND INTRACELLULAR SURVIVAL OF CAMPYLOBACTER-JEJUNI IN HUMAN EPITHELIAL-CELL CULTURES SO MICROBIAL PATHOGENESIS LA English DT Article DE CAMPYLOBACTER-JEJUNI; BACTERIAL INTERNALIZATION; EPITHELIAL CELLS; CYTOTOXICITY ID ENTEROINVASIVE ESCHERICHIA-COLI; HEP-2 CELLS; HELA-CELLS; YERSINIA-ENTEROCOLITICA; SALMONELLA-TYPHIMURIUM; NEISSERIA-GONORRHOEAE; BORDETELLA-PERTUSSIS; SHIGELLA-FLEXNERI; INVASION; INFECTION C1 NIAID,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. UNIV ARIZONA,DEPT VET SCI,TUCSON,AZ 85721. NR 40 TC 65 Z9 66 U1 2 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD NOV PY 1992 VL 13 IS 5 BP 357 EP 370 DI 10.1016/0882-4010(92)90079-4 PG 14 WC Immunology; Microbiology SC Immunology; Microbiology GA KR742 UT WOS:A1992KR74200003 PM 1297914 ER PT J AU BHATTACHARYA, A PRASAD, R SACKS, DL AF BHATTACHARYA, A PRASAD, R SACKS, DL TI IDENTIFICATION AND PARTIAL CHARACTERIZATION OF A LIPOPHOSPHOGLYCAN FROM A PATHOGENIC STRAIN OF ENTAMOEBA-HISTOLYTICA SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE ENTAMOEBA-HISTOLYTICA; LIPOPHOSPHOGLYCAN; GLYCOCONJUGATE ID LEISHMANIA-DONOVANI LIPOPHOSPHOGLYCAN; SURFACE-ANTIGEN; LECTIN AB An acidic glycoconjugate could be extracted from a delipidated residue fraction of [H-3]galactose, [H-3]mannose or [P-32]orthophosphate metabolically labeled Entamoeba histolytica with water/ethanol/diethylether/pyridine/NH4OH (15:15:5:1:0.017). The radioactively labeled glycoconjugate comprised 50-55% of the total [H-3]galactose label incorporated into macromolecules. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of the radiolabeled glycoconjugate showed two diffuse smears centering around 110 kDa and 45 kDa. Similar profiles were observed for both [H-3]galactose- and [P-32]orthophosphate-labeled glycoconjugate. No such bands were visible in [S-35]methionine-labeled material. The hydrophobic nature of this glycoconjugate was inferred from its chromatographic behavior on phenyl-Sepharose. The molecule was rendered hydrophilic after digestion with phosphatidylinositol-specific phospholipase C. It was also sensitive to deamination by nitrous acid. Mild acid hydrolysis led to its fragmentation into smaller molecules as revealed by Sepharose 4B chromatography. Paper chromatographic analysis of the depolymerized [H-3]galactose- and [H-3]mannose-labeled fragments revealed that each was wa sensitive to alkaline phosphatase. The major dephosphorylated fragment migrated as an apparent galactose and mannose containing disaccharide which migrated identically to the Galbeta1-4Man disaccharide derived from the lipophosphoglycan of Leishmania donovani. The above data support the existence of a major acidic glycoconjugate in E. histolytica bearing striking structural similarities to the lipophosphoglycan of Leishmania. C1 NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892. JAWAHARLAL NEHRU UNIV,SCH LIFE SCI,NEW DELHI 110067,INDIA. NR 25 TC 37 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD NOV PY 1992 VL 56 IS 1 BP 161 EP 168 DI 10.1016/0166-6851(92)90163-E PG 8 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA KA726 UT WOS:A1992KA72600015 PM 1474994 ER PT J AU ADAMS, JH FANG, XD KASLOW, DC MILLER, LH AF ADAMS, JH FANG, XD KASLOW, DC MILLER, LH TI IDENTIFICATION OF A CRYPTIC INTRON IN THE PLASMODIUM-VIVAX DUFFY BINDING-PROTEIN GENE SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Note DE PLASMODIUM; MALARIA; INVASION; ADHESIN; DUFFY BLOOD GROUP ANTIGEN; MICRONEME; EXON ID FALCIPARUM; ANTIGEN C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RP ADAMS, JH (reprint author), UNIV NOTRE DAME,DEPT BIOL SCI,NOTRE DAME,IN 46556, USA. RI Adams, John/G-1800-2015 OI Adams, John/0000-0003-3707-7979 NR 7 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD NOV PY 1992 VL 56 IS 1 BP 181 EP 184 DI 10.1016/0166-6851(92)90166-H PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA KA726 UT WOS:A1992KA72600018 PM 1474997 ER PT J AU LEESMILLER, SP SAKAGUCHI, K ULLRICH, SJ APPELLA, E ANDERSON, CW AF LEESMILLER, SP SAKAGUCHI, K ULLRICH, SJ APPELLA, E ANDERSON, CW TI HUMAN DNA-ACTIVATED PROTEIN-KINASE PHOSPHORYLATES SERINE-15 AND SERINE-37 IN THE AMINO-TERMINAL TRANSACTIVATION DOMAIN OF HUMAN P53 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID WILD-TYPE P53-PROTEIN; CELL-CYCLE CONTROL; RNA POLYMERASE-II; LARGE-T-ANTIGEN; 3T3 CELLS; SEQUENCE; BINDING; GENE; SUPPRESSION; INVITRO AB Human DNA-PK is a nuclear, serine/threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding substrates, including the tumor suppressor protein p53. To identify which p53 residues are phosphorylated, we examined DNA-PK's ability to phosphorylate synthetic peptides corresponding to human p53 sequences. Serines 15 and 37 in the amino-terminal transactivation domain of human p53, and serines 7 and 18 of mouse p53, were phosphorylated by DNA-PK in the context of synthetic peptides. Other serines in these p53 peptides, and serines in other p53 peptides, including peptides containing the serine 315 p34cdc2 site and the serine 392 casein kinase II site, were not recognized by DNA-PK or were phosphorylated less efficiently. Phosphorylation of the conserved serine 15 in human p53 peptides depended on the presence of an adjacent glutamine, and phosphorylation was inhibited by the presence of a nearby lysine. Phosphorylation of recombinant wild-type mouse p53 was inhibited at high DNA concentrations, suggesting that DNA-PK may phosphorylate p53 only when both are bound to DNA at nearby sites. Our study suggests that DNA-PK may have a role in regulating cell growth and indicates how phosphorylation of serine 15 in DNA-bound p53 could alter p53 function. C1 BROOKHAVEN NATL LAB, DEPT BIOL, UPTON, NY 11973 USA. NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. NR 59 TC 455 Z9 458 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1992 VL 12 IS 11 BP 5041 EP 5049 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JT845 UT WOS:A1992JT84500025 PM 1406679 ER PT J AU PORCU, P FERBER, A PIETRZKOWSKI, Z ROBERTS, CT ADAMO, M LEROITH, D BASERGA, R AF PORCU, P FERBER, A PIETRZKOWSKI, Z ROBERTS, CT ADAMO, M LEROITH, D BASERGA, R TI THE GROWTH-STIMULATORY EFFECT OF SIMIAN VIRUS-40 T-ANTIGEN REQUIRES THE INTERACTION OF INSULIN-LIKE GROWTH FACTOR-I WITH ITS RECEPTOR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN-BREAST-CANCER; CULTURED HUMAN-FIBROBLASTS; FACTOR-I RECEPTORS; IGF-1 RECEPTOR; SOMATOMEDIN-C; LEADER EXONS; CELL-CYCLE; GENE; EXPRESSION; SV40 AB We have used a plasmid expressing a temperature-sensitive (ts) mutant of simian virus 40 (SV40) T antigen, stably transfected into 3T3 cells, to study the role of insulinlike growth factor 1 (IGF-1) and its receptor in T-antigen-mediated growth. While 3T3 cells do not grow in serum-free medium, in 1% serum, or with the sole addition of either platelet-derived growth factor (PDGF) or IGF-1, cells expressing the tsA T antigen (BALB 58 cells) grow at 34-degrees-C in either PDGF or 1% serum but not in IGF-1. At the restrictive temperature (39.6-degrees-C), these cells can only grow in 10% serum. We show that BALB 58 cells, at 34-degrees-C, have a markedly increased expression of IGF-1 and IGF-1 mRNA and that their growth in 1% serum (at 34-degrees-C) is inhibited by an antisense oligodeoxynucleotide to the IGF-1 receptor RNA. When this tsA plasmid is stably transfected into cells constitutively overexpressing the human IGF-1 receptor cDNA, the resulting cell lines show a constitutively phosphorylated IGF-1 receptor and grow in serum-free medium at 34-degrees-C (but not at 39.6-degrees-C). A functional SV40 T antigen also increases the expression of a plasmid in which the reporter luciferase gene is under the control of a rat IGF-1 promoter. We conclude (i) that the SV40 T antigen induces the expression of IGF-1 and IGF-1 mRNA, at least in part by a transcriptional mechanism, thus altering the growth factors requirements, and (ii) that, in BALB/c3T3 cells, the SV40 T antigen necessitates a functional IGF-1 receptor for its growth-stimulating effect in low serum (or PDGF). C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,BLUEMLE LIFE SCI BLDG,233 S 10TH ST,PHILADELPHIA,PA 19107. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-53484, P01-CA52069] NR 58 TC 108 Z9 109 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 NOV PY 1992 VL 12 IS 11 BP 5069 EP 5077 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JT845 UT WOS:A1992JT84500028 PM 1406682 ER PT J AU RONG, S BODESCOT, M BLAIR, D DUNN, J NAKAMURA, T MIZUNO, K PARK, M CHAN, A AARONSON, S VANDEWOUDE, GF AF RONG, S BODESCOT, M BLAIR, D DUNN, J NAKAMURA, T MIZUNO, K PARK, M CHAN, A AARONSON, S VANDEWOUDE, GF TI TUMORIGENICITY OF THE MET PROTOONCOGENE AND THE GENE FOR HEPATOCYTE GROWTH-FACTOR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TYROSINE KINASE-ACTIVITY; SCATTER FACTOR; EPITHELIAL-CELLS; C-MET; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; MOUSE FIBROBLASTS; FACTOR RECEPTORS; CSF-1 RECEPTOR; PROTOONCOGENE AB The met proto-oncogene is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). It was previously shown that, like the oncogenic tpr-met, the mouse met proto-oncogene transforms NIH 3T3 cells. We have established NIH 3T3 cells stably expressing both human (Met(hu)) and mouse (Met(mu)) met proto-oncogene products. The protein products are properly processed and appear on the cell surface. NIH 3T3 cells express endogenous mouse HGF/SF mRNA, suggesting an autocrine activation mechanism for transformation by Met(mu). However, the tumor-forming activity of Met(hu) in NIH 3T3 cells is very low compared with that of Met(mu), but efficient tumorigenesis occurs when Met(hu) and HGF/SF(hu) are coexpressed. These results are consistent with an autocrine transformation mechanism and suggest further that the endogenous murine factor inefficiently activates the tumorigenic potential of Met(hu). The tumorigenicity observed with reciprocal chimeric human and mouse receptors that exchange external ligand-binding domains supports this conclusion. We also show that HGF/SF(hu) expressed in NIH 3T3 cells produces tumors in nude mice. C1 ADV BIOSCI LABS INC,BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. LUDWIG INST CANC RES,MONTREAL H3A 1A1,QUEBEC,CANADA. NIH,DIV CANC ETIOL,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. KYUSHU UNIV,FAC SCI,DEPT BIOL,FUKUOKA 812,JAPAN. RI Mizuno, Kensaku/G-8631-2015 FU NCI NIH HHS [N01-CO-74101] NR 58 TC 297 Z9 300 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 NOV PY 1992 VL 12 IS 11 BP 5152 EP 5158 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JT845 UT WOS:A1992JT84500037 PM 1406687 ER PT J AU HURD, YL HERKENHAM, M AF HURD, YL HERKENHAM, M TI INFLUENCE OF A SINGLE INJECTION OF COCAINE, AMPHETAMINE OR GBR-12909 ON MESSENGER-RNA EXPRESSION OF STRIATAL NEUROPEPTIDES SO MOLECULAR BRAIN RESEARCH LA English DT Article DE DYNORPHIN; ENKEPHALIN; SUBSTANCE-P; PSYCHOMOTOR STIMULANT; NUCLEUS ACCUMBENS ID NIGRAL DYNORPHIN SYSTEM; NUCLEUS ACCUMBENS; SUBSTANCE-P; RAT-BRAIN; DOPAMINERGIC REGULATION; IMMUNOREACTIVE NEURONS; INTRACEREBRAL DIALYSIS; UPTAKE INHIBITION; VENTRAL STRIATUM; INVIVO RELEASE AB The acute and long-term effects of a single injection of psychomotor stimulants (amphetamine (1.5 mg/kg i.p.), cocaine (30 mg/kg i.p.) and GBR 12909 (10 mg/kg i.p.)) were studied with in situ hybridization histochemistry to assess alterations in the mRNA expression of enkephalin, dynorphin and substance P in the striatum. The greatest alterations on mRNA levels of enkephalin, dynorphin and substance P were observed 2 h following the first administration of each drug compared to that observed following a second challenge injection 14 days later. Of the drugs tested, the dopamine uptake inhibitory agents cocaine and GBR 12909 acutely elevated mRNA levels of all three neuropeptides, while amphetamine elevated mRNA levels of substance P only. A second challenge administration of the stimulants 14 days subsequent to the initial single injection re-elevated the mRNA level of substance P. An overall tolerance is speculated to account for diminution of the enkephalin and dynorphin responses to a challenge injection while a relative sensitization is suggested for the enkephalin response due to a reduction in the baseline level of expression produced by the first injection. The data also show that there are regional variation within the striatum following systemic administration of psychomotor stimulants, with greater elevations in the sensorimotor dorsolateral striatum than in the ventromedial 'limbic' nucleus accumbens region. C1 NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. NR 51 TC 142 Z9 142 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV PY 1992 VL 16 IS 1-2 BP 97 EP 104 DI 10.1016/0169-328X(92)90198-K PG 8 WC Neurosciences SC Neurosciences & Neurology GA JW774 UT WOS:A1992JW77400012 ER PT J AU THAI, L LEE, PHK HO, J SUH, H HONG, JS AF THAI, L LEE, PHK HO, J SUH, H HONG, JS TI REGULATION OF PRODYNORPHIN GENE-EXPRESSION IN THE HIPPOCAMPUS BY GLUCOCORTICOIDS SO MOLECULAR BRAIN RESEARCH LA English DT Article DE ADRENALECTOMY; DEXAMETHASONE; HIPPOCAMPUS; DYNORPHIN; ENKEPHALIN; GENE REGULATION; OPIOID PEPTIDE; STEROID HORMONE ID MESSENGER-RNA LEVELS; RAT HIPPOCAMPUS; ACID; DYNORPHIN; BRAIN; CELLS; ADRENALECTOMY; ALTERS; DEXAMETHASONE; SURVIVAL AB The regulation of prodynorphin gene expression by glucocorticoids in the hippocampus was examined in rats that were adrenalectomized (ADX) either 7, 30, 60 and 90 days prior to sacrifice. Peptide levels in the hippocampus of ADX rats were determined by radioimmunoassay and immunocytochemistry. Prodynorphin (PDYN) mRNA was measured by Northern blot analysis and in situ hybridization. A time-dependent decrease in dynorphin A(1-8) (DYN) levels in the hippocampus (18% at 7 days; 44% at 30 days; 58% at 60 days) of ADX rats was found, which was accompanied by a comparable decrease in the abundance of PDYN mRNA. An in situ hybridization analysis revealed that both the number of positively hybridized cells and the number of silver grains per cell were decreased in the dentate gyrus after ADX. The administration of dexamethasone after surgery reversed the peptide and mRNA attenuation induced by ADX. ADX had no effect on the expression of proenkephalin mRNA or [Met5]-enkephalin immunoreactivity in the hippocampus. Examination of thionin-counterstained tissue showed that the dentate granule cell layer was intact. The decrement of DYN expression in this system is proposed to have resulted from the removal of glucocorticoid input and not dentate granule cell loss. This study provides the strong evidence for a differential susceptibility of these two opioid peptides in the hippocampus to the removal of glucocorticoids. In addition, these data provide support for a potentially selective, glucocorticoid-permissive component in PDYN gene expression. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CHAPEL HILL,NC 27514. NR 29 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV PY 1992 VL 16 IS 1-2 BP 150 EP 157 DI 10.1016/0169-328X(92)90205-P PG 8 WC Neurosciences SC Neurosciences & Neurology GA JW774 UT WOS:A1992JW77400019 ER PT J AU FOYT, HL LANAU, F WOLOSCHAK, M LEROITH, D ROBERTS, CT AF FOYT, HL LANAU, F WOLOSCHAK, M LEROITH, D ROBERTS, CT TI EFFECT OF GROWTH-HORMONE ON LEVELS OF DIFFERENTIALLY PROCESSED INSULIN-LIKE GROWTH FACTOR-I MESSENGER-RNAS IN TOTAL AND POLYSOMAL MESSENGER-RNA POPULATIONS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID IGF-I; RIBONUCLEIC-ACID; GENE-EXPRESSION; 5'-UNTRANSLATED REGIONS; TISSUE CONCENTRATIONS; LEADER EXONS; RAT; SEQUENCE; SITES; IDENTIFICATION AB As a result of multiple transcription initiation sites and differential splicing involving the first exons and alternate exon use, many insulin-like growth factor I (IGF-I) mRNA species are produced. In the present study, we have assessed the effect of GH on transcription start site usage and splicing and have determined the apparent in vivo translatability of IGF-I mRNAs with different 5'-untranslated region (UTR) sequences by comparing their abundance in total and polysomal RNA fractions from control, hypophysectomized, and GH-treated hypophysectomized rats. Hypophysectomy decreased the level of all IGF-I mRNA species, but those initiated at start site 3 in exon 1 and the major start site in exon 2 were preferentially reduced. These same variants were preferentially increased by GH treatment. Under all conditions, exon 1 mRNAs with shorter 5'-UTR sequences were enriched in polysomal RNA at the expense of IGF-I mRNAs with long 5'-UTR sequences, in accordance with the scanning model of translation initiation. Exon 2-derived mRNAs, on the other hand, which have short 5'-UTR sequences, were not enriched on polysomes, suggesting that some aspect of the exon 2-derived 5'-UTR other than length influences translation in vivo. These results demonstrate that transcription within exon 1 and between exons 1 and 2 is differentially regulated by GH status and that the variant IGF-I mRNA species resulting from the complex patterns of transcription initiation and splicing in these leader exons are differentially translated in vivo. RP FOYT, HL (reprint author), NIDDKD,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BLDG 10,ROOM 85239,BETHESDA,MD 20892, USA. NR 35 TC 36 Z9 36 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1992 VL 6 IS 11 BP 1881 EP 1888 DI 10.1210/me.6.11.1881 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB015 UT WOS:A1992KB01500015 PM 1282673 ER PT J AU CLARK, AJL BALLA, T JONES, MR CATT, KJ AF CLARK, AJL BALLA, T JONES, MR CATT, KJ TI STIMULATION OF EARLY GENE-EXPRESSION BY ANGIOTENSIN-II IN BOVINE ADRENAL GLOMERULOSA CELLS - ROLES OF CALCIUM AND PROTEIN-KINASE-C SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; TYROSINE PHOSPHORYLATION; ALDOSTERONE SECRETION; INTRACELLULAR CALCIUM; ADRENOCORTICAL-CELLS; SODIUM RESTRICTION; RECEPTOR SUBTYPES; FOS GENE; ACTIVATION; INDUCTION AB The adrenal glomerulosa cell is a major site of action of angiotensin II (AII), which binds to AT1 receptors to stimulate phosphoinositide hydrolysis and Ca2+ mobilization, and the subsequent production of aldosterone. AII also influences adrenal growth and proliferation and promotes thymidine incorporation in adrenocortical cells. In primary cultures of bovine glomerulosa cells, AII was found to induce the expression of several early growth response genes (c-fos, c-jun, JunB, and Krox 24). This effect of AII was dose-dependent and was blocked by [Sar1,Ile8] AII and the nonpeptide antagonist DuP 753, indicating that it is mediated by the AT1 subtype of the AII receptor. ACTH, which elevates cAMP in glomerulosa cells, was a relatively weak inducer of c-fos expression but was as potent as AII in stimulating the expression of JunB. ACTH did not further enhance the maximal effect of AII on c-fos expression. The role of the AII-induced cytoplasmic Ca2+ increase in generating the c-fos response was suggested by the ability of the Ca2+ ionophore ionomycin to induce c-fos expression. However, mobilization of intracellular Ca2+ by the Ca2+ ATPase inhibitor thapsigargin, as well as the stimulation of Ca2+ influx by depolarization with potassium, were less potent stimuli of c-fos expression. Omission of Ca2+ from the extracellular medium, which abolishes the plateau phase of the AII-induced Ca2+ signal without affecting the early increase due to Ca2+ mobilization, enhanced the early phase of the AII-induced c-fos response, indicating that Ca2+ also has an inhibitory effect on the early gene response. Activation of protein kinase C by phorbol 12-myristate, 13-acetate (PMA) also stimulated c-fos expression, but the combination of PMA and ionomycin did not further increase the c-fos response. Inhibition of protein kinase C by staurosporine, or its depletion by prolonged exposure to PMA, prevented the c-fos response to PMA but only partially inhibited the response to AII, suggesting the involvement of other factors in stimulus-transcription coupling from the AT1 receptor. C1 NICHHD,ENDOCRINOL & METAB RES BRANCH,BLDG 10,B1 L400,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. OI Balla, Tamas/0000-0002-9077-3335 NR 53 TC 55 Z9 55 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1992 VL 6 IS 11 BP 1889 EP 1898 DI 10.1210/me.6.11.1889 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB015 UT WOS:A1992KB01500016 PM 1336125 ER PT J AU ROBERTS, AB VODOVOTZ, Y ROCHE, NS SPORN, MB NATHAN, CF AF ROBERTS, AB VODOVOTZ, Y ROCHE, NS SPORN, MB NATHAN, CF TI ROLE OF NITRIC-OXIDE IN ANTAGONISTIC EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA AND INTERLEUKIN-1-BETA ON THE BEATING RATE OF CULTURED CARDIAC MYOCYTES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ESCHERICHIA-COLI LIPOPOLYSACCHARIDE; ISCHEMIA REPERFUSION INJURY; AORTIC ENDOTHELIAL-CELLS; SMOOTH-MUSCLE CELLS; INTERFERON-GAMMA; MURINE MACROPHAGES; NITROGEN-OXIDES; FACTOR-ALPHA; SYNTHASE AB We have recently shown that transforming growth factor-beta (TGFbeta) acts in an autocrine manner to maintain the beating rate of neonatal rat cardiac myocytes cultured in serum-free medium on cardiac fibroblast matrix. Interleukin-1beta (IL-1beta) suppresses the myocyte-beating rate, and TGFbeta antagonizes this effect. We now show that TGFbeta and IL-1beta also have antagonistic effects on the secretion of nitric oxide (NO) by these myocytes, and that NO secretion, the activity of NO synthase (NOS), and expression of the inducible form of NOS correlate inversely with the effects of these two agents on the beating rate. Western blot analysis shows that treatment of myocytes with TGFbeta antagonizes the induction of NOS after treatment with IL-1beta. Release of NO, induced by IL-1beta is dependent upon the availability of the substrate, L-arginine, and is suppressed by a competitive inhibitor, N(G)-monomethyl-L-arginine. L-Arginine (>0.25 mM) also suppresses, and N(G)-monomethyl-L-arginine (>0.5 mM) enhances the myocyte-beating rate. Treatment with IL-1beta, but not TGFbeta, increases cellular cGMP, presumably by activation of guanylate cyclase by NO. Methylene blue, an inhibitor of guanylate cyclase, reverses the suppression of beating caused by IL-1beta. Bacterial lipopolysaccharide, present in the serum-free medium, is a coinducer of NO secretion. The suppressive effects of NO on the beating rate can be overcome by altering either the set of cytokines employed to induce NO or the matrix on which the myocytes are cultured, demonstrating that additional parameters are also involved in regulation of the beating rate. C1 CORNELL UNIV,MED CTR,COLL MED,DEPT MED,DIV HEMATOL ONCOL,BEATRICE & SAMUEL A SEAVER LAB,NEW YORK,NY 10021. RP ROBERTS, AB (reprint author), NCI,CHEMOPREVENT LAB,BLDG 4,ROOM C629,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-43610] NR 48 TC 161 Z9 162 U1 1 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1992 VL 6 IS 11 BP 1921 EP 1930 DI 10.1210/me.6.11.1921 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB015 UT WOS:A1992KB01500019 PM 1282674 ER PT J AU TENG, CT LIU, YH YANG, NY WALMER, D PANELLA, T AF TENG, CT LIU, YH YANG, NY WALMER, D PANELLA, T TI DIFFERENTIAL MOLECULAR MECHANISM OF THE ESTROGEN ACTION THAT REGULATES LACTOFERRIN GENE IN HUMAN AND MOUSE SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID LACTOTRANSFERRIN GENE; REPRODUCTIVE-TRACT; EXPRESSION; PROMOTER; RECEPTOR; CELLS; DNA; IDENTIFICATION; TRANSCRIPTION; LOCALIZATION AB The 5'-flanking region of the human lactoferrin gene was isolated from a human placental genomic library. This genomic clone contains a 16-kilobase pair (kbp) insert and produces seven fragments when digested with the SacI restriction enzyme. We sequenced one of the fragments that comprises 1294 bp of the 5'-flanking sequence, 79 bp of the first exon, and 690 bp of the first intron. A major transcription start site was mapped by primer extension. The region immediately upstream from the transcription initiation site following the first exon is abundant in G and C nucleotides. In the promoter and 5'-flanking region within a 300-bp stretch (-465 to -165) of the DNA, we found a noncanonical TATA box (ATAAA), CAAT-like sequence (CAAC) and sequences homologous to the consensus SP1 binding site, Pu.1/Sp.1 binding element (PU box), two half-palindromic estrogen response elements (EREs; GGTCA), an imperfect ERE (GGTCAAGGCGATC), and a sequence resembling the chicken ovalbumin upstream promoter transcription factor (COUP-TF) binding site (GTCTCACAGGTCA). The COUP-TF binding site and the imperfect ERE shared five nucleotides (GGTCA). With the exception of the two half-palindromic EREs, the elements with very well matched sequences were also found in the corresponding positions in the mouse lactoferrin gene. The synthetic oligonucleotide, including the 26 bp of COUP/ERE sequence, was cloned before the SV40 promoter in a chloramphenicol acetyltransferase reporter construct. These chimeric plasmids were transiently transfected into human endometrium carcinoma RL95-2 cells to assess hormone responsiveness. We found that the COUP/ERE element acted as an enhancer in response to estrogen stimulation. In vitro DNase I footprinting analysis showed binding of the estrogen receptor on the imperfect ERE. in contrast to the mouse lactoferrin COUP/ERE element, COUP-TF does not interact with this element, as demonstrated by band shift assay and site-directed mutagenesis. Therefore, the molecular mechanisms of the estrogen action that govern the lactoferrin gene expression differ between mouse and human. C1 DUKE UNIV,MED CTR,DEPT OBSTET GYNECOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DIV HEMATOL ONCOL,DURHAM,NC 27710. RP TENG, CT (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,BOX 12233,MD 1301,RES TRIANGLE PK,NC 27709, USA. NR 51 TC 68 Z9 70 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1992 VL 6 IS 11 BP 1969 EP 1981 DI 10.1210/me.6.11.1969 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB015 UT WOS:A1992KB01500024 PM 1480183 ER PT J AU FRANCIS, CL STARNBACH, MN FALKOW, S AF FRANCIS, CL STARNBACH, MN FALKOW, S TI MORPHOLOGICAL AND CYTOSKELETAL CHANGES IN EPITHELIAL-CELLS OCCUR IMMEDIATELY UPON INTERACTION WITH SALMONELLA-TYPHIMURIUM GROWN UNDER LOW-OXYGEN CONDITIONS SO MOLECULAR MICROBIOLOGY LA English DT Article ID TISSUE-CULTURE CELLS; ESCHERICHIA-COLI; HELA-CELLS; SHIGELLA-FLEXNERI; MAMMALIAN-CELLS; LINE CACO-2; INVASION; CLONING; ACCUMULATION; PENETRATION AB Salmonella typhimurium grown under oxygen-limiting conditions were found to enter into, elicit actin filament rearrangement in, and effect morphological changes upon HEp-2 cells within 15 min after infection. Video microscopy revealed that host cell morphological changes associated with entry began within 1 min of productive adherence. Polarized Caco-2 cell morphology was affected 40 s after infection with low-oxygen-grown S. typhimurium. Stationary-phase S. typhimurium did not elicit these phenomena within this time-period even when adherence was enhanced with the afimbrial adhesin, AFA-I. Thus, environmental cues regulate S. typhimurium invasion factors, allowing for immediate entry into host cells. Additionally, actin filament rearrangement and morphological changes in the eukaryotic host cell are essential for entry and occur within minutes of infection. C1 NIAID,ROCKY MT LAB,HAMILTON,MT 59840. RP FRANCIS, CL (reprint author), STANFORD UNIV,MED CTR,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305, USA. FU NIAID NIH HHS [AI26195]; NIDDK NIH HHS [DK38707] NR 32 TC 157 Z9 161 U1 1 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1992 VL 6 IS 21 BP 3077 EP 3087 DI 10.1111/j.1365-2958.1992.tb01765.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA JW888 UT WOS:A1992JW88800001 PM 1360615 ER PT J AU FELDER, CC VELUZ, JS WILLIAMS, HL BRILEY, EM MATSUDA, LA AF FELDER, CC VELUZ, JS WILLIAMS, HL BRILEY, EM MATSUDA, LA TI CANNABINOID AGONISTS STIMULATE BOTH RECEPTOR-MEDIATED AND NONRECEPTOR-MEDIATED SIGNAL TRANSDUCTION PATHWAYS IN CELLS TRANSFECTED WITH AND EXPRESSING CANNABINOID RECEPTOR CLONES SO MOLECULAR PHARMACOLOGY LA English DT Article ID INHIBIT ADENYLATE-CYCLASE; LIGAND-BINDING SYSTEMS; CEREBRAL-CORTEX SLICES; ARACHIDONIC-ACID; MAMMALIAN-CELLS; RAT-BRAIN; DELTA-9-TETRAHYDROCANNABINOL; LOCALIZATION; PROSTAGLANDINS; ACTIVATION AB The physiologic activity of (-)-DELTA9-tetrahydrocannabinol, the most active component of marijuana, and of many synthetic cannabimimetics may be mediated either through receptor binding and functional coupling to specific signal transduction pathways or through nonspecific interaction with cell membrane components. The cloning of the human and rat cannabinoid receptors has provided the opportunity to investigate the binding properties and signal transduction pathways directly associated with these receptors. Cannabinoid receptor cDNA was transfected into and stably expressed in fibroblast cell lines that do not contain native cannabinoid receptors, thus allowing comparison with untransfected cells. Binding constants measured using [H-3]CP55,940 indicated that the rat and human cloned cannabinoid receptors were similar to native cannabinoid receptors measured in brain and neural cell lines. The cloned receptors coupled to the inhibition of cAMP accumulation, as previously demonstrated. CP55,940 binding and inhibition of cAMP accumulation were absent in untransfected cells. Cannabinoid agonist-stimulated release of arachidonic acid and increase in intracellular calcium were observed in both transfected and untransfected cells. Stereoselectivity of cannabinoid agonists was demonstrated for binding and functional inhibition of cAMP accumulation, but not for the release of arachidonic acid and intracellular calcium. Therefore, cannabinoid agonists can stimulate signaling pathways through both receptor- and non-receptor-mediated pathways in the same cell. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. RP FELDER, CC (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 44 TC 226 Z9 230 U1 1 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1992 VL 42 IS 5 BP 838 EP 845 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JY342 UT WOS:A1992JY34200015 PM 1331766 ER PT J AU BASILE, AS PAUL, IA MIRCHEVICH, A KUIJPERS, G DECOSTA, B AF BASILE, AS PAUL, IA MIRCHEVICH, A KUIJPERS, G DECOSTA, B TI MODULATION OF (+)-[H-3]PENTAZOCINE BINDING TO GUINEA-PIG CEREBELLUM BY DIVALENT-CATIONS SO MOLECULAR PHARMACOLOGY LA English DT Article ID ETORPHINE-INACCESSIBLE SITES; CENTRAL NERVOUS-SYSTEM; SIGMA-RECEPTORS; RAT-BRAIN; AUTORADIOGRAPHIC LOCALIZATION; -LABELED SKF-10047; (+)-SKF 10,047; HIGH-AFFINITY; PHENCYCLIDINE; LIGANDS AB The ability of cations to modulate the binding of the sigma1 receptor-selective ligand (+)-[H-3]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[H-3]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ much-greater-than La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ much-greater-than Mg2+ > Ca2+. The inhibition of 1,3-[H-3]di(2-tolyl)guanidine binding to the sigma2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[H-3]pentazocine binding. Although monovalent cations decreased the K(d) for (+)-[H-3]pentazocine binding, divalent cations split (+)-[H-3]pentazocine binding into low and high affinity components. The B(max) of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[H-3]pentazocine with the sigma1 receptor without altering the dissociation rate. (+)-[H-3]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[H-3]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[H-3]pentazocine binding to the sigma1, receptor, to reveal multiple affinity states. These sites do not represent sigma1 to sigma2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. RP BASILE, AS (reprint author), NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892, USA. NR 47 TC 28 Z9 29 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1992 VL 42 IS 5 BP 882 EP 889 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JY342 UT WOS:A1992JY34200020 PM 1279378 ER PT J AU RUNGER, TM POOT, M KRAEMER, KH AF RUNGER, TM POOT, M KRAEMER, KH TI ABNORMAL PROCESSING OF TRANSFECTED PLASMID DNA IN CELLS FROM PATIENTS WITH ATAXIA TELANGIECTASIA SO MUTATION RESEARCH LA English DT Article DE CHROMOSOME BREAKAGE; DNA JOINING; XERODERMA-PIGMENTOSUM; CARCINOGENESIS; IMMUNE DEFICIENCY; RADIOSENSITIVITY ID BLOOMS SYNDROME CELLS; LIGASE-I; GENE; LINES; HETEROZYGOTES; BREAKAGE; LOCUS AB In order to assess spontaneous mutability and accuracy of DNA joining in ataxia telangiectasia, a disorder with spontaneous chromosome breakage, the replicating shuttle vector plasmid, pZ189, was transfected into SV40 virus-transformed fibroblasts from ataxia telangiectasia patients. The ataxia telangiectasia fibroblasts showed elevated frequency of micronuclei, a measure of chromosome breakage. The spontaneous mutation frequency was normal with circular plasmids passed through the ataxia telangiectasia line. These results were compared to those with transformed fibroblasts from a patient with xeroderma pigmentosum, and from a normal donor. Mutation analysis revealed spontaneous point mutations and deletions in the plasmids with all 3 cell lines, however, insertions or complex mutations were only detectable with the ataxia telangiectasia line. To assess DNA-joining ability, linear plasmids which require joining of the DNA ends by host cell enzymes for survival, were transfected into the cells. We found a 2.4-fold less efficient DNA joining in ataxia telangiectasia fibroblasts (p = 0.04) and a 2.0-fold higher mutation frequency (p < 0.01) in the recircularized plasmids than with the normal line. Plasmid DNA joining and mutation frequency were normal with the xeroderma pigmentosum fibroblasts. These findings with the ataxia telangiectasia fibroblasts of abnormal types of spontaneous mutations in the transfected plasmid and inefficient, error-prone DNA joining may be related to the increased chromosome breakage in these cells. In contrast, an EB virus-transformed ataxia telangiectasia lymphoblast line with normal frequency of micronuclei showed normal types of spontaneous mutations in the transfected plasmid and normal frequency of DNA joining which was error-prone. These data indicate that mechanisms that produce chromosome breakage in ataxia telangiectasia cells can be reflected in processing of plasmid vectors. C1 NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892. UNIV WURZBURG,DEPT HUMAN GENET,W-8700 WURZBURG,GERMANY. RI Poot, Martin/F-9427-2010 FU Intramural NIH HHS [Z01 BC004517-31] NR 33 TC 24 Z9 24 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 NOV PY 1992 VL 293 IS 1 BP 47 EP 54 DI 10.1016/0921-8777(92)90007-P PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA JT394 UT WOS:A1992JT39400006 PM 1383810 ER PT J AU KHAN, AS WILCOX, AS POLYMEROPOULOS, MH HOPKINS, JA STEVENS, TJ ROBINSON, M ORPANA, AK SIKELA, JM AF KHAN, AS WILCOX, AS POLYMEROPOULOS, MH HOPKINS, JA STEVENS, TJ ROBINSON, M ORPANA, AK SIKELA, JM TI SINGLE PASS SEQUENCING AND PHYSICAL AND GENETIC-MAPPING OF HUMAN BRAIN CDNAS SO NATURE GENETICS LA English DT Article ID HUMAN GENOME; DNA; REPEAT; AMPLIFICATION; POLYMORPHISMS; POLYMERASE AB We have performed single pass sequencing of 1,024 human brain cDNAs, over 900 of which seem to represent new human genes. Library prescreening with total brain cDNA significantly reduced repeated sequencing of highly represented cDNAs. A subset of sequenced cDNAs were physically mapped to their chromosomal locations using gene-specific STS primers derived from 3' untranslated regions. We have also determined that human brain cDNAs represent a rich source of gene-associated polymorphic markers. Microsatellite-containing cDNAs can be physically mapped and converted to highly informative genetic markers, thus facilitating integration of the human physical, expression and genetic maps. C1 VET ADM SCHIZOPHRENIA CTR,MOLEC BIOL LAB,DENVER,CO 80220. NIMH,BIOCHEM GENET LAB,WASHINGTON,DC 20032. RP KHAN, AS (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262, USA. NR 25 TC 156 Z9 160 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1992 VL 2 IS 3 BP 180 EP 185 DI 10.1038/ng1192-180 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA JW165 UT WOS:A1992JW16500005 PM 1345165 ER PT J AU DEMICHELI, E SONCRANT, TT AF DEMICHELI, E SONCRANT, TT TI AGE-DEPENDENT CEREBRAL METABOLIC EFFECTS OF UNILATERAL NUCLEUS BASALIS MAGNOCELLULARIS ABLATION IN RATS SO NEUROBIOLOGY OF AGING LA English DT Article DE AGING; ALZHEIMERS DISEASE; NUCLEUS BASALIS MAGNOCELLULARIS; FOREBRAIN CHOLINERGIC NEURONS; EXCITOTOXIC LESIONS; [C-14]2-DEOXY-D-GLUCOSE; CEREBRAL GLUCOSE UTILIZATION; RAT ID CHOLINE-ACETYLTRANSFERASE ACTIVITY; NEUROTRANSMITTER-RELATED ENZYMES; POSITRON EMISSION TOMOGRAPHY; IBOTENIC ACID INJECTIONS; GLUCOSE-UTILIZATION; ALZHEIMER-TYPE; SENILE DEMENTIA; COGNITIVE IMPAIRMENTS; MEMORY LOSS; LESIONS AB To investigate the age-dependent functional importance of cholinergic neocortical inputs, and to explore whether cortical cholinergic denervation in aged animals might better model the cerebral metabolic changes of Alzheimer's disease, the effects of unilateral ablation of the nucleus basalis magnocellularis (NBM) on cerebral glucose metabolism were studied in young and aged rats. Regional cerebral metabolic rates for glucose (rCMRglc) were determined, using the [C-14]deoxyglucose method, in 48 brain regions of 3- and 24-month old Fischer-344 rats at 3, 7, 14 and 28 days after stereotaxic injection of ibotenate into the right NBM, and in sham-operated animals at 3 and 14 days later. For both ages the peak effect of unilateral NBM ablation occurred 3 days later: in young rats, rCMRglc was significantly reduced (compared to the contralateral side) in all 24 anterior cortical areas examined (mean decline 20%), whereas in aged animals, only 9 of 24 areas showed a significant decline in glucose utilization, and the magnitude of rCMRglc reduction (9%) was smaller. Near complete recovery of rCMRglc occurred by 7 days in young and old rats. We conclude that the basalo-cortical cholinergic projection plays a smaller role in neocortical function of aged rats, possibly because its tonic activity is reduced. Both young and aged rats undergo cortical metabolic normalization after unilateral NBM ablation; hence the NBM-lesioned aged rat is not a better model of the progressive decline in rCMRglc that occurs in Alzheimer's disease. C1 NIA,NEUROSCI LAB,10-6C103,BETHESDA,MD 20892. RP SONCRANT, TT (reprint author), NIA,NEUROSCI LAB,10-6C103,BETHESDA,MD 20892, USA. NR 74 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1992 VL 13 IS 6 BP 687 EP 695 DI 10.1016/0197-4580(92)90091-B PG 9 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA KD085 UT WOS:A1992KD08500007 PM 1491734 ER PT J AU SCHAPIRO, MB HAXBY, JV GRADY, CL AF SCHAPIRO, MB HAXBY, JV GRADY, CL TI NATURE OF MENTAL-RETARDATION AND DEMENTIA IN DOWN-SYNDROME - STUDY WITH PET, CT, AND NEUROPSYCHOLOGY SO NEUROBIOLOGY OF AGING LA English DT Article DE DOWN SYNDROME; CHROMOSOME-21; MENTAL RETARDATION; DEMENTIA; ALZHEIMERS DISEASE; PET SCAN; 18FDG; BRAIN METABOLISM; CT SCAN; NEUROPSYCHOLOGY ID FAMILIAL ALZHEIMERS-DISEASE; CEREBRAL GLUCOSE-UTILIZATION; ADULT DOWNS-SYNDROME; PRESENILE-DEMENTIA; HEALTHY-MEN; NEUROFIBRILLARY TANGLES; PATHOLOGICAL-CHANGES; BRAIN MORPHOMETRICS; MOSAIC TRISOMY-21; NEURITIC PLAQUES AB Recent evidence suggests that Alzheimer's disease is an etiologically heterogeneous disorder. A human model of Alzheimer's disease exists that avoids such problems of etiologic heterogeneity. Down syndrome (DS), trisomy 2 1, is a genetic disorder in which an extra portion of chromosome 21 leads to mental retardation, short stature, and phenotypic abnormalities. Prior investigations by others have shown that DS subjects over 40 years of age demonstrate neuropathologic and neurochemical defects postmortem that are virtually indistinguishable from those found in brains of Alzheimer's disease patients and a universal cognitive deterioration more severe in demented than nondemented older DS subjects. In our study, these nondemented older DS subjects show a distinctive pattern of age-related deficits, while a more global pattern is seen in demented older DS subjects. Dementia occurs in 40% of older DS subjects. We find that in older demented DS subjects positron emission tomography (PET) shows identical patterns of abnormal glucose metabolism as those described previously in Alzheimer's disease patients, selectively involving the phylogenetically newer association areas of parietal and temporal neocortices but sparing primary sensory and motor regions. Further, we find in older demented DS patients quantitative computer-assisted tomography (CT) indicates accelerated neuronal loss and brain atrophy, similar to that previously shown in Alzheimer's disease patients. As a potential use of the DS model, we observed a case of DS with dementia but without mental retardation. This case suggests that expression of dementia in DS may involve genes on chromosome 21 other than in the "obligatory" distal segment of the q arm. Alternatively, differential expression of genes on the q arm of chromosome 21 might cause dementia without phenotypic features and mental retardation. RP SCHAPIRO, MB (reprint author), NIA,CTR CLIN,BRAIN AGING & DEMENTIA SECT,NEUROSCI LAB,BLDG 10,RM 6C414,BETHESDA,MD 20892, USA. NR 98 TC 71 Z9 71 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1992 VL 13 IS 6 BP 723 EP 734 DI 10.1016/0197-4580(92)90096-G PG 12 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA KD085 UT WOS:A1992KD08500012 PM 1491738 ER PT J AU TIZABI, Y AGUILERA, G AF TIZABI, Y AGUILERA, G TI DESENSITIZATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS FOLLOWING PROLONGED ADMINISTRATION OF CORTICOTROPIN-RELEASING HORMONE OR VASOPRESSIN SO NEUROENDOCRINOLOGY LA English DT Article DE STRESS; ADRENOCORTICOTROPIN; GLUCOCORTICOIDS; CORTICOTROPIN-RELEASING HORMONE RECEPTORS; MINIPUMP INFUSION; VASOPRESSIN ID RAT ANTERIOR-PITUITARY; PROOPIOMELANOCORTIN GENE-EXPRESSION; FACTOR-LIKE IMMUNOREACTIVITY; BETA-ENDORPHIN RELEASE; ADRENOCORTICAL RESPONSES; IMMOBILIZATION STRESS; ARGININE VASOPRESSIN; FACTOR STIMULATION; MEDIAN-EMINENCE; SECRETION AB The responses of the hypothalamic-pituitary-adrenal axis during chronic stress are characterized by normal or slightly elevated plasma ACTH, increased hypothalamic corticotropin-releasing hormone (CRH) and vasopressin secretion, decreased pituitary CRH receptors and hypersensitivity of the ACTH and glucocorticoid responses to a novel stress. To determine the role of CRH and vasopressin in the pituitary hyperresponsiveness to a superimposed stress, pituitary CRH receptors and plasma ACTH responses were measured in rats receiving minipump infusions of CRH or a combination of CRH and vasopressin (VP), 50 ng/min of each for 50 h. Rats were killed by decapitation with or without exposure to ether vapor for 5 min or immobilization for 15 or 30 min, and blood was collected for ACTH and corticosterone determinations. The pituitary CRH receptor concentration measured by binding I-125-Tyr-oCRH, was reduced by 45 and 80% in CRH- and CRH-plus-VP-infused rats, respectively, with no changes in receptor affinity. Acute stress by ether exposure or immobilization had no effect on pituitary CRH receptors. Adrenal weight was significantly increased, and thymus weight decreased in CRH-infused animals, indicating activation of the pituitary adrenal axis. However, in contrast to the responses following chronic stress, the increases in plasma ACTH in response to an injection of 10 mug/kg CRH or acute stress were significantly lower in CRH- and CRH-plus-VP-infused rats. Furthermore the content and release of ACTH from quartered pituitaries were also decreased in chronically treated rats. The data indicate that sustained pituitary stimulation by CRH either alone or in combination with VP does not account for the enhanced ACTH responses to a novel stimulus observed following chronic stress. C1 NICHHD, DEB, BLDG 10, RM 10N-262, BETHESDA, MD 20892 USA. HOWARD UNIV, COLL MED, DEPT PHARMACOL, WASHINGTON, DC 20001 USA. NR 43 TC 67 Z9 67 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD NOV PY 1992 VL 56 IS 5 BP 611 EP 618 DI 10.1159/000126283 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA KF098 UT WOS:A1992KF09800002 PM 1336816 ER PT J AU GLOWA, JR GEYER, MA GOLD, PW STERNBERG, EM AF GLOWA, JR GEYER, MA GOLD, PW STERNBERG, EM TI DIFFERENTIAL STARTLE AMPLITUDE AND CORTICOSTERONE RESPONSE IN RATS SO NEUROENDOCRINOLOGY LA English DT Article DE STARTLE; STRESS; STRAIN-DEPENDENT DIFFERENCES ID WALL-INDUCED ARTHRITIS; ACOUSTIC STARTLE; LEWIS RATS; HABITUATION; HORMONE; FEAR AB Different rat strains exhibit large differences in hypothalamic pituitary-adrenal activity that have been used to determine the role of the neuroendocrine system in susceptibility to autoimmune disease. To further characterize potential behavioral correlates of these differences, the amplitude of the acoustic (ASR) and tactile (TSR) startle response and the corticosterone response to acoustic startle stimuli were compared between two histocompatible strains, Lewis (LEW/N) and Fischer (F344/N) rats, as well as outbred Harlan Sprague-Dawley (SD) rats. Startle stimuli elicited larger ASR and TSR in LEW/N rats than in F344/N rats, with SD rats exhibiting an intermediate response. The ASR habituated at a similar rate in LEW/N and F344 rats, while the ASR did not habituate in SD rats. After handling and placement in the startle chambers, the three strains did not differ in control levels of corticosterone. In contrast, exposure to acoustic startle stimuli increased corticosterone 5-fold in F344/N rats and 2-fold in SD rats, but had no effect on corticosterone in LEW/N rats. These findings suggested an inverse relationship between the amplitude of the ASR and hypothalamic-pituitary-adrenal activation across strains. This relationship was further supported by a high negative correlation between corticosterone level and ASR amplitude within the F344/N group. C1 UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,LA JOLLA,CA 92093. RP GLOWA, JR (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BLDG 14D,ROOM 311,BETHESDA,MD 20892, USA. FU NIDA NIH HHS [DA02925]; NIMH NIH HHS [MH00188] NR 19 TC 79 Z9 79 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD NOV PY 1992 VL 56 IS 5 BP 719 EP 723 DI 10.1159/000126298 PG 5 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA KF098 UT WOS:A1992KF09800017 PM 1488104 ER PT J AU MINAGAWA, H YOSHIDA, T ITOYAMA, Y MORA, CA ALBERT, P MORI, R AF MINAGAWA, H YOSHIDA, T ITOYAMA, Y MORA, CA ALBERT, P MORI, R TI NEUTRALIZING ANTIBODIES AGAINST HTLV-I IN HTLV-I-ASSOCIATED MYELOPATHY TROPICAL SPASTIC PARAPARESIS (HAM TSP) PATIENTS AND ASYMPTOMATIC CARRIERS SO NEUROLOGY LA English DT Note ID T-CELL LEUKEMIA; VIRUS TYPE-I; INDUCTION; SYNCYTIA AB We tested serum specimens from patients with HAM/TSP and asymptomatic HTLV-I carriers from endemic areas of Japan, Jamaica, Colombia, and Chile for neutralizing antibodies against HTLV-I. The data suggest a trend for neutralizing activity to be found more frequently in the sera from HAM/TSP patients than in sera from asymptomatic carriers. The result of this study emphasizes the importance of determining biologic properties of the envelope glycoprotein of HTLV-I. C1 NATL INST NEUROL DISORDERS & STROKE,DIV INTRAMURAL RES,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD. NATL INST NEUROL DISORDERS & STROKE,DIV INTRAMURAL RES,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD. RP MINAGAWA, H (reprint author), KYUSHU UNIV,SCH MED,DEPT VIROL,MAIDASHI 3-1-1,HIGASHI KU,FUKUOKA 812,JAPAN. NR 10 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1992 VL 42 IS 11 BP 2210 EP 2212 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA JY627 UT WOS:A1992JY62700030 PM 1436540 ER PT J AU HEMPSTEAD, BL RABIN, SJ KAPLAN, L REID, S PARADA, LF KAPLAN, DR AF HEMPSTEAD, BL RABIN, SJ KAPLAN, L REID, S PARADA, LF KAPLAN, DR TI OVEREXPRESSION OF THE TRK TYROSINE KINASE RAPIDLY ACCELERATES NERVE GROWTH FACTOR-INDUCED DIFFERENTIATION SO NEURON LA English DT Article ID INTERMEDIATE FILAMENT PROTEIN; FOS-INDEPENDENT PATHWAYS; TRANSIN GENE-EXPRESSION; PHOSPHOLIPASE-C-GAMMA; HUMAN NGF RECEPTOR; PC12 CELLS; HIGH-AFFINITY; PHEOCHROMOCYTOMA CELLS; PROTOONCOGENE PRODUCT; NEURONAL DIFFERENTIATION AB To investigate the role of the gp140trk receptor tyrosine kinase in nerve growth factor (NGF)-induced differentiation, we have overexpressed gp140trk in the NGF-responsive PC12 cell line. Here we demonstrate that overexpression of gp140trk results in marked changes in NGF-induced differentiation. Whereas PC12 cells elaborated neurites after 2 days of continuous exposure to NGF, PC12 cells overexpressing gp140trk by 20-fold (trk-PC12) began this process within hours. Compared with wild-type PC12 cells, trk-PC12 exhibited an increase in both high and low affinity NGF-binding sites. Furthermore, trk-PC12 cells displayed an enhanced level of NGF-dependent gp140trk autophosphorylation, and this activity was sustained for many hours following ligand binding. The tyrosine phosphorylation or activity of several cellular proteins, such as PLC-gamma1, PI-3 kinase, and Erk1 and the expression of the mRNA for the late response gene transin were also sustained as a consequence of gp140trk overexpression. The data indicate that overexpression of gp140trk in PC12 cells markedly accelerates NGF-induced differentiation pathways, possibly through the elevation of gp140trk tyrosine kinase activity. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,MMCL,EUKARYOT SIGNAL TRANSDUCT GRP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,MGL,MOLEC EMBRYOL SECT,FREDERICK,MD 21701. RP HEMPSTEAD, BL (reprint author), CORNELL UNIV,SCH MED,DIV HEMATOL,NEW YORK,NY 10021, USA. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101] NR 73 TC 303 Z9 303 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1992 VL 9 IS 5 BP 883 EP 896 DI 10.1016/0896-6273(92)90241-5 PG 14 WC Neurosciences SC Neurosciences & Neurology GA JY552 UT WOS:A1992JY55200008 PM 1384575 ER PT J AU HULIHANGIBLIN, BA PARK, YD AULAKH, CS GOLDMAN, D AF HULIHANGIBLIN, BA PARK, YD AULAKH, CS GOLDMAN, D TI REGIONAL-ANALYSIS OF 5-HT1A-RECEPTORS AND 5-HT2-RECEPTORS IN THE FAWN-HOODED RAT SO NEUROPHARMACOLOGY LA English DT Article DE [H-3]8-OH-DPAT; [H-3]KETANSERIN, 5-HT1A-RECEPTORS; 5-HT2-RECEPTORS; RAT BRAIN ID SPRAGUE-DAWLEY RATS; BINDING-SITES; IMIPRAMINE BINDING; BRAIN; 5-HT; AUTORECEPTORS; DEFICIENCY; PLATELETS; RESPONSES; MEDIATION AB The Fawn-Hooded strain of rats exhibits a hemorrhagic disorder, known as platelet storage pool deficiency. In addition to the platelet dysfunction, there is an altered response to certain serotonin drugs. To assess the characteristics of the binding to 5-HT1A and 5-HT2 receptors in this strain, regions of the brain from Fawn-Hooded, Sprague-Dawley and Wistar male rats were examined. The drug [H-3]8-OH-DPAT was used to label 5-HT1A receptors and the K(d) values for frontal cortex, hippocampus, striatum, hypothalamus and brainstem were similar in all three strains of rat. As with the 5-HT1A receptors, no differences were observed in the K(d) values for 5-HT2 receptors, in any of the regions examined, among the three strains. However, the B(max) for the binding of [H-3]8-OH-DPAT in the striatum and brainstem of Fawn-Hooded rats was less than in the Sprague--Dawley and Wistar animals. Furthermore, 5-HT2 receptors displayed a greater B(max) value in the striatum and in the frontal cortex of Fawn-Hooded animals, compared to Sprague-Dawley and Wistar rats. These differences in receptors are consistent with previous studies in which Fawn-Hooded rats were found to have altered serotonergic function, relative to Wistar and Sprague-Dawley animals. C1 NIMH,CTR CLIN,CLIN SCI LAB,BETHESDA,MD 20892. RP HULIHANGIBLIN, BA (reprint author), NIAAA,NEUROGENET LAB,BETHESDA,MD 20892, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 23 TC 30 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 1992 VL 31 IS 11 BP 1095 EP 1099 DI 10.1016/0028-3908(92)90004-9 PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA JZ644 UT WOS:A1992JZ64400003 PM 1475019 ER PT J AU GOYER, PF SCHULZ, PM SEMPLE, WE GROSS, M NORDAHL, TE KING, AC WEHR, TA COHEN, RM AF GOYER, PF SCHULZ, PM SEMPLE, WE GROSS, M NORDAHL, TE KING, AC WEHR, TA COHEN, RM TI CEREBRAL GLUCOSE-METABOLISM IN PATIENTS WITH SUMMER SEASONAL AFFECTIVE-DISORDER SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE METABOLISM; SUMMER SEASONAL AFFECTIVE DISORDER; REGIONAL CEREBRAL METABOLIC RATE OF GLUCOSE; CONTINUOUS PERFORMANCE TASK ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY; PANIC DISORDER; PREFRONTAL SUBSTRATE; SUSTAINED ATTENTION; SCHIZOPHRENIA; RATES; DEPRESSION; DYSFUNCTION; ANXIETY AB Positron emission tomography scans of nine patients diagnosed with summer seasonal affective disorder (SSAD) were compared with scans of 45 normal control subjects to investigate differences in brain glucose metabolism. All subjects performed an auditory discrimination task beginning several minutes before injection of F-18-deoxyglucose and continuing for 30 minutes after injection. Regional glucose metabolic rates were extracted from 60 rectangular regions of interest measured in five planes selected as atlas matches from 28 total slices. Statistically significant differences between patients with SSAD and normal control subjects were found in cerebral glucose metabolic rate and also in normalized regional glucose metabolic rates in the orbital frontal cortex and in the left inferior parietal lobule. C1 NIMH,CLIN PSYCHOBIOL SECT,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,SCH MED,DIV NEUROPSYCHIAT IMAGING,CLEVELAND,OH 44106. NIMH,CLIN BRAIN IMAGING SECT,BETHESDA,MD 20892. RP GOYER, PF (reprint author), UNIV HOSP CLEVELAND,DEPT PSYCHIAT,2040 ABINGTON RD,CLEVELAND,OH 44106, USA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 34 TC 15 Z9 15 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 1992 VL 7 IS 3 BP 233 EP 240 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA JQ581 UT WOS:A1992JQ58100008 PM 1388646 ER PT J AU SCHEFFEL, U DANNALS, RF WONG, DF YOKOI, F CARROLL, FI KUHAR, MJ AF SCHEFFEL, U DANNALS, RF WONG, DF YOKOI, F CARROLL, FI KUHAR, MJ TI DOPAMINE TRANSPORTER IMAGING WITH NOVEL, SELECTIVE COCAINE ANALOGS SO NEUROREPORT LA English DT Article DE DOPAMINE TRANSPORTER; DOPAMINE UPTAKE; COCAINE; RTI-55; RTI-121; RTI-122; SPECT IMAGING ID H-3 WIN-35,428; BINDING-SITES; INVIVO; BRAIN AB RTI-121 AND RTI-122 are 3beta-substituted phenyltropane analogs of cocaine that have high, selective binding affinity for dopamine transporters. [I-123]RTI-121 and [I-123]RTI-122 bind to dopamine transporters in vivo after intravenous administration and permit imaging of the transporters. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DIV NUCL MED & RADIAT HLTH SCI,BALTIMORE,MD 21205. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA 32845]; NIDA NIH HHS [DA 05477]; NINDS NIH HHS [NS 15080] NR 13 TC 36 Z9 36 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV PY 1992 VL 3 IS 11 BP 969 EP 972 DI 10.1097/00001756-199211000-00005 PG 4 WC Neurosciences SC Neurosciences & Neurology GA KA083 UT WOS:A1992KA08300005 PM 1482766 ER PT J AU BOJA, JW MCNEILL, RM LEWIN, AH ABRAHAM, P CARROLL, FI KUHAR, MJ AF BOJA, JW MCNEILL, RM LEWIN, AH ABRAHAM, P CARROLL, FI KUHAR, MJ TI SELECTIVE DOPAMINE TRANSPORTER INHIBITION BY COCAINE ANALOGS SO NEUROREPORT LA English DT Article DE DOPAMINE TRANSPORTER; DOPAMINE UPTAKE; COCAINE; RTI-55 ID LIGAND-BINDING; RECEPTORS AB SEVERAL isopropyl and phenyl esters of 3beta-(4-substituted phenyl) tropan-2beta-carboxylic acid analogs of cocaine are relatively more potent and selective than cocaine and some other compounds in inhibiting dopamine uptake. These analogs can be used as binding ligands and as tools for elucidating the mechanisms of action of cocaine. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,MOLEC PHARMACOL LAB,POB 5180,BALTIMORE,MD 21224. RES TRIANGLE INST,DEPT ORGAN & MED CHEM,RES TRIANGLE PK,NC 27709. FU NIDA NIH HHS [DA05477] NR 19 TC 56 Z9 56 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV PY 1992 VL 3 IS 11 BP 984 EP 986 DI 10.1097/00001756-199211000-00009 PG 3 WC Neurosciences SC Neurosciences & Neurology GA KA083 UT WOS:A1992KA08300009 PM 1482769 ER PT J AU SAITO, K MARKEY, SP HEYES, MP AF SAITO, K MARKEY, SP HEYES, MP TI EFFECTS OF IMMUNE ACTIVATION ON QUINOLINIC ACID AND NEUROACTIVE KYNURENINES IN THE MOUSE SO NEUROSCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY; INFECTED RHESUS MACAQUES; TUMOR NECROSIS FACTOR; CEREBROSPINAL-FLUID; INTERFERON-GAMMA; RAT-BRAIN; 3-HYDROXYANTHRANILIC ACID; TRYPTOPHAN DEGRADATION; HIV-1 INFECTION AB Accumulation of quinolinic acid and neuroactive kynurenines derived from tryptophan are of potential significance in human neuropathologic diseases because of their neurotoxic and convulsant properties. Clinical studies have established that sustained elevations of quinolinic acid, L-kynurenine and kynurenic acid within the cerebrospinal fluid occur in patients with a broad spectrum of inflammatory diseases and correlate with markers of immune activation and interferon-gamma activity. The present study describes an animal model that replicates these clinical observations and investigates the role of interferon-gamma as a mediator between immune activation and increased kynurenine pathway metabolism. Marked elevations in quinolinic acid, L-kynurenine and 3-hydroxykynurenine as well as an increased ratio of quinolinic acid: kynurenic acid in brain occurred 24 h after systemic pokeweed mitogen administration to C57BL6 mice. In plasma, L-tryptophan and kynurenic acid levels were reduced by pokeweed mitogen, while the concentrations Of L-kynurenine, 3-hydroxykynurenine and quinolinic acid were increased. Interferon-gamma, pokeweed mitogen and lipopolysaccharide induced indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway, and increased both L-kynurenine and quinolinic acid concentrations of brain and systemic tissues, particularly in the lung, gastrointestinal tract and spleen. In contrast, hepatic tryptophan-2,3-dioxygenase activity was either reduced or unaffected. Increases in kynurenine pathway metabolism were sustained in mice given daily injections of interferon-gamma for seven days and subsequent responses to interferon-gamma were further enhanced. In contrast, daily administration of lipopolysaccharide was associated with subsequent attenuated responsiveness (tolerance) to lipopolysaccharide, pokeweed mitogen and interferon-gamma. Systemic administration of a monoclonal antibody to mouse interferon-gamma either attenuated or abolished the responses of kynurenine pathway metabolism to pokeweed mitogen and interferon-gamma. We conclude that acute and chronic increases in quinolinic acid and neuroactive kynurenines follow immune stimulation in mice, and result from indoleamine-2,3-dioxygenase induction. The results demonstrate that interferon-gamma is an important mediator between immune stimulation and indoleamine-2,3-dioxygenase induction. These increases in kynurenine pathway metabolism closely parallel the responses documented in patients with a broad spectrum of inflammatory diseases. Mice treated with immune stimuli are a useful model to investigate the relationships between immune activation and kynurenine pathway metabolism. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,ROOM 3D40,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 81 TC 136 Z9 137 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD NOV PY 1992 VL 51 IS 1 BP 25 EP 39 DI 10.1016/0306-4522(92)90467-G PG 15 WC Neurosciences SC Neurosciences & Neurology GA JY672 UT WOS:A1992JY67200005 PM 1465184 ER PT J AU DUTHU, A DEBUIRE, B ROMANO, J EHRHART, JC FISCELLA, M MAY, E APPELLA, E MAY, P AF DUTHU, A DEBUIRE, B ROMANO, J EHRHART, JC FISCELLA, M MAY, E APPELLA, E MAY, P TI P53 MUTATIONS IN RAJI CELLS - CHARACTERIZATION AND LOCALIZATION RELATIVE TO OTHER BURKITTS LYMPHOMAS SO ONCOGENE LA English DT Article ID CELLULAR TUMOR-ANTIGEN; CDNA CLONE; SUPPRESSOR GENE; ONCOGENE; TRANSFORMATION; EXPRESSION; PROTEIN; LINES; DNA; IMMORTALIZATION AB The nuclear phosphoprotein p53 is an important regulator of cell proliferation in normal cells. Interestingly, the gene encoding p53 has usually undergone mutations in a wide range of tumor types. Recent studies of the p53 gene in Burkitt's lymphomas have demonstrated that mutations are extremely common, and in fact it is rare that both alleles of the p53 gene in these tumors are not inactivated by mutation or deletion. We present here genetic data regarding the status of the p53 gene in the Burkitt lymphoma cell line, Raji. As is typical for this type of tumor, both alleles have undergone point mutations. Further, statistical analysis of available data from a large number of Burkitt's lymphomas indicates an apparent tumor-specific distribution of p53 mutations. The possibility that specific mutations of the p53 gene may be important for different tumor types is discussed. C1 CNRS,UPR 275,BP 8,F-94801 VILLEJUIF,FRANCE. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 43 TC 50 Z9 52 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1992 VL 7 IS 11 BP 2161 EP 2167 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA JW665 UT WOS:A1992JW66500008 PM 1437144 ER PT J AU HALABAN, R RUBIN, JS FUNASAKA, Y COBB, M BOULTON, T FALETTO, D ROSEN, E CHAN, A YOKO, K WHITE, W COOK, C MOELLMANN, G AF HALABAN, R RUBIN, JS FUNASAKA, Y COBB, M BOULTON, T FALETTO, D ROSEN, E CHAN, A YOKO, K WHITE, W COOK, C MOELLMANN, G TI MET AND HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR SIGNAL TRANSDUCTION IN NORMAL MELANOCYTES AND MELANOMA-CELLS SO ONCOGENE LA English DT Article ID AUTOCRINE MOTILITY FACTOR; TYROSINE KINASE RECEPTOR; HUMAN GASTRIC-CARCINOMA; C-MET; MOLECULAR-CLONING; MURINE MELANOCYTES; EPITHELIAL-CELLS; REGULATED KINASES; TRANSFORMING GENE; PROTEIN-KINASES AB The proto-oncogene c-MET encodes a transmembrane tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF stimulates the proliferation and motility of various cell types. Because HGF/SF is also a melanocyte mitogen, we investigated the biological role of HGF/SF, including c-Met expression, activation and signal transduction, in normal and malignant human melanocytes. We show that HGF/SF is mitogenic in the presence of synergistic factors, such as basic fibroblast growth factor (bFGF) and mast cell growth factor (MGF) and that, by itself, it stimulates the motility of normal human melanocytes. The ligand also maintained high levels of tyrosinase activity and melanin content in theses cells. Signal transduction by HGF/SF included phosphorylation of tyrosyl residues on c-Met, a cascade of tyrosine phosphorylations on several other proteins and activation of microtubule-associated protein kinase/extracellular signal-regulated kinase. Met expression and activity are normal in human melanomas, and constitutive activity of HGF/SF in retrovirally infected autonomously proliferative mouse melanocytes is insufficient to confer the malignant phenotype. Our findings suggest that activation of Met in response to HGF/SF may contribute to malignant progression synergistically with the aberrant expression of bFGF in malignant melanocytes and that, in addition, the peptide may promote dispersion of factor-dependent melanocytes from early stages of primary melanomas to ectopic sites. C1 NCI,FREDERICK CANC RES & DEV,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PATHOL,WINSTON SALEM,NC 27103. YALE UNIV,SCH MED,DEPT RADIAT THERAPY,NEW HAVEN,CT 06510. UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235. YALE UNIV,SCH MED,DEPT PLAST SURG,NEW HAVEN,CT 06510. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP HALABAN, R (reprint author), YALE UNIV,SCH MED,DEPT DERMATOL,333 CEDAR ST,POB 3333,NEW HAVEN,CT 06510, USA. OI Cobb, Melanie/0000-0003-0833-5473 FU NCI NIH HHS [5-R29-CA44542]; NIAMS NIH HHS [1RO1-AR39848]; NIDDK NIH HHS [DK 34128] NR 73 TC 162 Z9 163 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1992 VL 7 IS 11 BP 2195 EP 2206 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA JW665 UT WOS:A1992JW66500012 PM 1331934 ER PT J AU HALL, NG HERSHEY, JC KESSLER, LG STOTTS, RC AF HALL, NG HERSHEY, JC KESSLER, LG STOTTS, RC TI A MODEL FOR MAKING PROJECT FUNDING DECISIONS AT THE NATIONAL-CANCER-INSTITUTE SO OPERATIONS RESEARCH LA English DT Article AB This paper describes the development of a model for making project funding decisions at The National Cancer Institute (NCI). The American Stop Smoking Intervention Study (ASSIST) is a multiple-year, multiple-site demonstration project, aimed at reducing smoking prevalence. The initial request for ASSIST proposals was answered by about twice as many states as could be funded. Scientific peer review of the proposals was the primary criterion used for funding decisions. However, a modified Delphi process made explicit several criteria of secondary importance. A structured questionnaire identified the relative importance of these secondary criteria, some of which we incorporated into a composite preference function. We modeled the proposal funding decision as a zero-one program, and adjusted the preference function and available budget parametrically to generate many suitable outcomes. The actual funding decision, identified by our model, offers significant advantages over manually generated solutions found by experts at NCI. C1 UNIV PENN,WHARTON SCH,PHILADELPHIA,PA 19104. NCI,APPL RES BRANCH,BETHESDA,MD 20892. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. RP HALL, NG (reprint author), OHIO STATE UNIV,COLUMBUS,OH 43210, USA. OI Hall, Nicholas/0000-0003-4484-9252 NR 13 TC 21 Z9 22 U1 0 U2 10 PU OPERATIONS RESEARCH SOC AMER PI LINTHICUM HTS PA 901 ELKRIDGE LANDING RD, STE 400, LINTHICUM HTS, MD 21090-2920 SN 0030-364X J9 OPER RES JI Oper. Res. PD NOV-DEC PY 1992 VL 40 IS 6 BP 1040 EP 1052 DI 10.1287/opre.40.6.1040 PG 13 WC Management; Operations Research & Management Science SC Business & Economics; Operations Research & Management Science GA KD112 UT WOS:A1992KD11200002 PM 10123313 ER PT J AU KOVACIK, V HIRSCH, J KOVAC, P GRUTZMACHER, HF AF KOVACIK, V HIRSCH, J KOVAC, P GRUTZMACHER, HF TI MASS-ANALYZED ION KINETIC-ENERGY AND COLLISIONALLY INDUCED DISSOCIATION MASS-SPECTRA OF CLUSTERS OF ACETYLATED XYLO-OLIGOSACCHARIDES WITH PROTONATED AMMONIA AND METHYLAMINE SO ORGANIC MASS SPECTROMETRY LA English DT Article ID SPECTROMETRY; XYLANS AB Per-O-acetylated methyl glycosides of D-xylan-type di- and trisaccharides were studied by mass-analysed ion kinetic energy (MIKE) and collisionally induced dissociation (CID) mass spectrometry using protonated ammonia and methylamine, respectively, as reaction gases in chemical ionization (CI). The oligosaccharides form abundant cluster ions, [M + NH4]+ or [M + CH3NH3]+, and the main fragmentation of these ions in the MIKE and CID spectra is the cleavage of interglycosidic linkages. Thus, CI (NH3) or CI (CH3NH2) spectra in combination with the MIKE or CID spectra allow the molecular masses, the masses of monosaccharide units and the branching point in oligosaccharides to be established. In the case of disaccharides, it is possible to distinguish the (1 --> 2) linkage from the other types of linkages. C1 NIDDK,BETHESDA,MD 20892. UNIV BIELEFELD,FAC CHEM,W-4800 BIELEFELD,GERMANY. RP KOVACIK, V (reprint author), SLOVAK ACAD SCI,INST CHEM,CS-84238 BRATISLAVA,CZECHOSLOVAKIA. NR 12 TC 2 Z9 2 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0030-493X J9 ORG MASS SPECTROM JI Org. Mass Spectrom. PD NOV PY 1992 VL 27 IS 11 BP 1322 EP 1324 DI 10.1002/oms.1210271129 PG 3 WC Chemistry, Organic; Spectroscopy SC Chemistry; Spectroscopy GA JZ936 UT WOS:A1992JZ93600027 ER PT J AU KODA, J LUDLOW, CL AF KODA, J LUDLOW, CL TI AN EVALUATION OF LARYNGEAL MUSCLE ACTIVATION IN PATIENTS WITH VOICE TREMOR SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID ABDUCTOR SPASMODIC DYSPHONIA; DYSTONIA SPASTIC DYSPHONIA; BOTULINUM TOXIN INJECTION; ADDUCTOR; THERAPY AB Eight patients with voice tremor were studied to characterize laryngeal muscle involvement. Electromyographic (EMG) recordings were made from intrinsic laryngeal muscles, simultaneously with some extrinsic laryngeal muscles, respiratory movement, and voice recordings during respiration, whisper, and phonation. Spectral measures were used to determine the tremor frequency and the prominence of spectral peaks in the EMG, respiratory and acoustic signals, while correlation coefficients were computed between pairs of tremulous EMG signals to measure the synchrony of tremor between muscles. The intrinsic laryngeal muscles were tremulous during respiration and speech, with the thyroarytenoid most often involved. Tremor was also detected in some of the extrinsic muscle recordings and the percentage of muscles with tremor was higher during phonation than during whisper or respiration. Time delays were found between tremor oscillations in laryngeal muscles. Because the thyroarytenoid was affected in all the patients studied, botulinum toxin injections may be beneficial in treatment of this voice disorder. C1 NIDOCD,DIV INTRAMURAL RES,VOICE & SPEECH SECT,BETHESDA,MD. OI Ludlow, Christy/0000-0002-2015-6171 NR 30 TC 38 Z9 39 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 1992 VL 107 IS 5 BP 684 EP 696 PG 13 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA JZ476 UT WOS:A1992JZ47600010 PM 1437206 ER PT J AU MCAREAVEY, D FANANAPAZIR, L AF MCAREAVEY, D FANANAPAZIR, L TI SUPPRESSION OF INCESSANT VENTRICULAR-TACHYCARDIA IN HYPERTROPHIC CARDIOMYOPATHY ASSOCIATED WITH IMPROVEMENT OF SEVERE LEFT-VENTRICULAR DYSFUNCTION SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE INCESSANT VENTRICULAR TACHYCARDIA; HYPERTROPHIC CARDIOMYOPATHY; LEFT VENTRICULAR DYSFUNCTION AB A 32-year-old black man presented with a history of palpitations since childhood and two syncopal episodes. He was found to have incessant ventricular tachycardia, impaired left ventricular contraction (ejection fraction 9%), and nonobstructive hypertrophic cardiomyopathy. Procainamide abolished the arrhythmia and the ejection fraction rose to 22% in sinus rhythm. Later treatment was switched to amiodarone, which suppressed the ventricular tachycardia but necessitated pacemaker implantation. He has remained well during the subsequent 2 years. Left ventricular ejection fraction has increased to 47% measured in paced rhythm. The improvement in left ventricular function has been attributed to suppression of the incessant ventricular tachycardia. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 6 TC 2 Z9 2 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD NOV PY 1992 VL 15 IS 11 BP 1642 EP 1645 DI 10.1111/j.1540-8159.1992.tb02948.x PN 1 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA JW803 UT WOS:A1992JW80300006 PM 1279528 ER PT J AU NAHIN, RL HYLDEN, JLK HUMPHREY, E AF NAHIN, RL HYLDEN, JLK HUMPHREY, E TI DEMONSTRATION OF DYNORPHIN-A 1-8 IMMUNOREACTIVE AXONS CONTACTING SPINAL-CORD PROJECTION NEURONS IN A RAT MODEL OF PERIPHERAL INFLAMMATION AND HYPERALGESIA SO PAIN LA English DT Article DE PAIN; OPIATES; KAPPA RECEPTORS; IMMUNOCYTOCHEMISTRY; SPINOPARABRACHIAL TRACT ID SUPERFICIAL DORSAL HORN; SENSORY GANGLION NEURONS; OPIOID RECEPTOR AGONISTS; ROOT-GANGLIA; NOR-BINALTORPHIMINE; HIPPOCAMPUS INVITRO; INDUCED ANALGESIA; AFFERENT-FIBERS; PYRAMIDAL CELLS; TRACT NEURONS AB Using a double-labeling technique, we evaluated the input of afferents immunoreactive for dynorphin peptide onto a population of lumbar spinal neurons contributing to the spinoparabrachial tract in rats with 1 inflamed hind paw. We found that the frequency and distribution with which dynorphin immunoreactive varicosities were in apposition to projection neurons varied according to neuron location. In particular, neurons in the superficial dorsal horn and neck of the dorsal horn receive a high degree of dynorphin input. We also determined that unilateral peripheral inflammation is associated with both an increase in the number of projection neurons receiving detectable DYN input and in the frequency of this input onto a given neuron, with the largest increase seen in the superficial dorsal horn. Since almost all superficial dorsal horn neurons contributing to the spinoparabrachial tract respond either exclusively or maximally to noxious stimulation, our data supports dynorphin's involvement in nociception. RP NAHIN, RL (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 30,RM B-20,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 61 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 1992 VL 51 IS 2 BP 135 EP 143 DI 10.1016/0304-3959(92)90254-9 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA KA576 UT WOS:A1992KA57600002 PM 1362457 ER PT J AU GRACELY, RH LYNCH, SA BENNETT, GJ AF GRACELY, RH LYNCH, SA BENNETT, GJ TI PAINFUL NEUROPATHY - ALTERED CENTRAL PROCESSING MAINTAINED DYNAMICALLY BY PERIPHERAL INPUT SO PAIN LA English DT Article DE REFLEX SYMPATHETIC DYSTROPHY; ALLODYNIA; TOURNIQUET-CUFF BLOCK; LOCAL-ANESTHETIC BLOCK; SENSORY ASSESSMENT; NOCICEPTION; SYMPATHETICALLY MAINTAINED PAIN; SYMPATHETICALLY INDEPENDENT PAIN ID RAT SPINAL-CORD; DORSAL HORN NEURONS; NERVE INJURY; MECHANICAL HYPERALGESIA; NEUROGENIC HYPERALGESIA; POLYMODAL NOCICEPTORS; INTRADERMAL INJECTION; PROJECTION NEURONS; C-NOCICEPTORS; STIMULATION AB We performed sensory assessments before and during diagnostic tourniquet-cuff and local anesthetic blocks in 4 patients diagnosed with reflex sympathetic dystrophy (RSD). All patients complained of mechano-allodynia; lightly touching the skin evoked an intense pain sensation. At detection levels, electrical stimuli were perceived as painful, suggesting that the mechano-allodynia was mediated by Abeta low-threshold mechanoreceptor afferents. Abeta-mediated allodynia was further supported by reaction time latencies to painful electrical stimuli at threshold for A-fiber activation and, in 1 patient, by differential cuff blocks which abolished Abeta function and allodynia while thermal sensation (warm and cold) were preserved. Local anesthetic block of painful foci associated with previous trauma abolished mechano-allodynia, cold allodynia, and spontaneous pain in all patients and relieved the motor symptoms in 1 patient with tonic contractures of the toes. Tactile and thermal perception in the previously allodynic area was preserved. When the local anesthetic block waned, spontaneous pain, allodynia, and motor symptoms returned. We propose a model of neuropathic pain in which ongoing nociceptive afferent input from a peripheral focus dynamically maintains altered central processing that accounts for allodynia, spontaneous pain, and other sensory and motor abnormalities. Blocking the peripheral input causes the central processing to revert to normal, abolishing the symptoms for the duration of the block. The model accounts for sympathetically maintained (SMP) and sympathetically independent (SIP) pain. The peripheral input can be independent of sympathetic activity or driven completely or in part by activity in sympathetic efferents or by circulating catecholamines. The shared final common pathway may explain the common features of SMP and SIP. RP GRACELY, RH (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 10,ROOM 1N-103,BETHESDA,MD 20892, USA. NR 59 TC 553 Z9 557 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 1992 VL 51 IS 2 BP 175 EP 194 DI 10.1016/0304-3959(92)90259-E PG 20 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA KA576 UT WOS:A1992KA57600007 PM 1484715 ER PT J AU LEWIS, M RAMSAY, DS SUOMI, SJ AF LEWIS, M RAMSAY, DS SUOMI, SJ TI VALIDATING CURRENT IMMUNIZATION PRACTICE WITH YOUNG INFANTS SO PEDIATRICS LA English DT Article ID CORTISOL RESPONSE; CIRCUMCISION; ANESTHESIA C1 NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. RP LEWIS, M (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PEDIAT,INST STUDY CHILD DEV,NEW BRUNSWICK,NJ 08903, USA. NR 10 TC 10 Z9 10 U1 2 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1992 VL 90 IS 5 BP 771 EP 773 PG 3 WC Pediatrics SC Pediatrics GA KF503 UT WOS:A1992KF50300023 PM 1408553 ER PT J AU HALL, CB EASTON, JG GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G BAKER, CJ MERENSTEIN, GB CASSADY, G ERENBERG, A ESCOBEDO, M FELDMAN, BH FERNBACH, SA KIRKPATRICK, BV KLEINMAN, LI LIGHT, IJ ALLEN, A DOOLEY, SL KENNER, C WRIGHT, LL KRUMMEL, TM AF HALL, CB EASTON, JG GRANOFF, DM GROMISCH, DS HALSEY, NA KOHL, S MARCUSE, EK MARKS, MI NANKERVIS, GA PICKERING, LK SCOTT, GB STEELE, RW PETER, G BART, KJ BROOME, C HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, G BAKER, CJ MERENSTEIN, GB CASSADY, G ERENBERG, A ESCOBEDO, M FELDMAN, BH FERNBACH, SA KIRKPATRICK, BV KLEINMAN, LI LIGHT, IJ ALLEN, A DOOLEY, SL KENNER, C WRIGHT, LL KRUMMEL, TM TI GUIDELINES FOR PREVENTION OF GROUP-B STREPTOCOCCAL (GBS) INFECTION BY CHEMOPROPHYLAXIS SO PEDIATRICS LA English DT Article ID PRETERM LABOR; RISK-FACTORS; DISEASE; COLONIZATION; PENICILLIN; INFANTS; SEPSIS; URINE C1 NIH,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. NICHHD,BETHESDA,MD 20892. RP HALL, CB (reprint author), CTR DIS CONTROL,ATLANTA,GA 30333, USA. RI Steele, Russell/A-6075-2011 NR 26 TC 104 Z9 104 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 NOV PY 1992 VL 90 IS 5 BP 775 EP 778 PG 4 WC Pediatrics SC Pediatrics GA KF503 UT WOS:A1992KF50300025 ER PT J AU SCHEIDT, PC KESSEL, SS AF SCHEIDT, PC KESSEL, SS TI RESEARCH IN BEHAVIORAL PEDIATRICS - REPORT OF A CONFERENCE MAY 22-24, 1989 - INTRODUCTION SO PEDIATRICS LA English DT Editorial Material C1 MATERNAL & CHILD HLTH BUR,ROCKVILLE,MD. RP SCHEIDT, PC (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 NOV PY 1992 VL 90 IS 5 SU S BP 785 EP 786 PN 2 PG 2 WC Pediatrics SC Pediatrics GA KF833 UT WOS:A1992KF83300001 ER PT J AU ROTHMAN, RB MAHBOUBI, A BYKOV, V KIM, CH DECOSTA, BR JACOBSON, AE RICE, KC AF ROTHMAN, RB MAHBOUBI, A BYKOV, V KIM, CH DECOSTA, BR JACOBSON, AE RICE, KC TI PROBING THE OPIOID RECEPTOR COMPLEX WITH (+)-TRANSSUPERFIT .2. EVIDENCE THAT MU-LIGANDS ARE NONCOMPETITIVE INHIBITORS OF THE DELTA-CX OPIOID PEPTIDE BINDING-SITE SO PEPTIDES LA English DT Article DE OPIOID RECEPTORS; LIGAND BINDING; ENKEPHALIN; RECEPTOR SUBTYPES ID 2-SITE ALLOSTERIC MODEL; RAT-BRAIN MEMBRANES; DIFFERENTIAL ANTAGONISM; LEUCINE-H-3 ENKEPHALIN; OPIATE RECEPTOR; CROSS-TOLERANCE; SUBTYPES; AFFINITY; MORPHINE; AGONIST AB Previous studies delineated two classes of delta binding sites; a delta binding site not associated with the opioid receptor complex, termed the delta(ncx) site, and a delta site associated with the opioid receptor complex, termed the delta(cx) site. The delta(ncx), site has high affinity for [D-Pen2,D-Pen5]enkephalin, and is synonymous with what is now identified as the delta1 binding site. Pretreatment of membranes with the delta-selective acylating agents FIT. or (+)-trans-SUPERFIT, deplete membranes of the delta(ncx) binding site, which permits the selective labeling of the delta(cx) binding site with [H-3][D-Ala2,Leu5]lenkephalin. The present study compared the properties of the delta(cx) binding site present in brain membranes pretreated with (+)-trans-SUPERFIT with the properties of the delta(cx) site present in untreated membranes. The major findings are: 1) pretreatment of membranes with (+)-trans-SUPERFIT decreased the IC50 values of delta-preferring drugs, and increased the lC50 values of mu-preferring drugs, for the delta(cx) binding site; 2) the degree of delta selectivity was highly correlated with the magnitude of the (+)-trans-SUPERFIT-induced shift in the IC50 values; 3) the ligand-selectivity patterns of the mu and delta(cx) sites present in (+)-trans-SUPERFIT-pretreated membranes were poorly correlated; 4) whereas mu-preferring drugs were noncompetitive inhibitors of [H-3][D-Ala2,Leu5]enkephalin binding to the delta(cx) site, delta-preferring drugs were competitive inhibitors. Viewed collectively, these data support the hypothesis that the mu and delta(cx) binding sites are distinct, provide additional evidence for delta receptor heterogeneity, and suggest that (+)-trans-SUPERFIT-pretreated membranes will provide a useful preparation for studying the delta(cx) binding site. C1 NIDDK,MED CHEM LAB,BETHESDA,MD 21224. RP ROTHMAN, RB (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 38 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV-DEC PY 1992 VL 13 IS 6 BP 1137 EP 1143 DI 10.1016/0196-9781(92)90020-4 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA KF124 UT WOS:A1992KF12400019 PM 1337378 ER PT J AU XU, H PARTILLA, JS DECOSTA, BR RICE, KC ROTHMAN, RB AF XU, H PARTILLA, JS DECOSTA, BR RICE, KC ROTHMAN, RB TI INTERACTION OF OPIOID-PEPTIDES AND OTHER DRUGS WITH MULTIPLE DELTA-NCX BINDING-SITES IN RAT-BRAIN - FURTHER EVIDENCE FOR HETEROGENEITY SO PEPTIDES LA English DT Article DE OPIOID PEPTIDES; DELTA-NCX BINDING SITES; DRUG INTERACTION ID GUINEA-PIG BRAIN; RECEPTOR COMPLEX; OPIATE RECEPTORS; HIGH-AFFINITY; SELECTIVITY; ANTAGONIST; SUBTYPES; AGONIST; LIGAND; NUCLEOTIDES AB Recent pharmacological data strongly support the hypothesis of delta receptor subtypes as mediators of both supraspinal and spinal antinocieption (delta1 and delta2 receptors). In vitro ligand binding data, which are fully supportive of the in vivo data, are still lacking. A previous study indicated that [H-3][D-Ala2,D-Leu5]enkephalin labels two binding sites in membranes depleted of mu binding sites by pretreatment with the site-directed acylating agent, 2-(p-ethoxybenzyl)-i-diethylaminoethyl-5-isothiocyanatobenzimidazole-HCl (BIT). The main goal of the present study was to develop a ligand-selectivity profile of the two delta(ncx) binding sites. The data indicated that naltrindole and oxymorphindole were relatively selective for site 1 (20-fold). [D-Ser2,Thr6]Enkephalin and deltorphin-II were only 2.7-fold and 2.2-fold selective for site 1. [D-Pen2,D-Pen5]Enkephalin and deltorphin-I were 80-fold and 38-fold selective for site 2. 3-Iodo-Tyr-D-Ala-Gly-Phe-D-Leu was 52-fold selective for site 1. Morphine had moderate affinity for site 1 (K(i) = 16 nM), and was about 11-fold selective for site 1. Thus, of the 10 drugs studied, only DPDPE and DELT-I were selective for site 2. Viewed collectively with other data, it is likely that the delta1 receptor and the delta(ncx) binding site are synonymous. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 35 TC 21 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV-DEC PY 1992 VL 13 IS 6 BP 1207 EP 1213 DI 10.1016/0196-9781(92)90030-7 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA KF124 UT WOS:A1992KF12400029 PM 1337380 ER PT J AU WITT, DM WINSLOW, JT INSEL, TR AF WITT, DM WINSLOW, JT INSEL, TR TI ENHANCED SOCIAL INTERACTIONS IN RATS FOLLOWING CHRONIC, CENTRALLY INFUSED OXYTOCIN SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE CHRONIC OT; SOCIAL INTERACTIONS; PHYSICAL CONTACT; AUTOGROOMING; ANALGESIA; ANXIETY ID CORTICOTROPIN-RELEASING FACTOR; PENILE ERECTION; SEXUAL-BEHAVIOR; PRAIRIE VOLES; VASOPRESSIN; SECRETION; HAMSTERS; NOVELTY AB Most studies investigating the behavioral effects of centrally administered oxytocin (OT) have been confined to single acute injections followed by brief behavioral observations lasting up to 90 min. The present study examines the behavioral effects of chronic, centrally administered OT in male rats observed continuously for prolonged periods of time. Either artificial cerebrospinal fluid or OT was centrally infused (via osmotic minipump) to gonadally intact male rats. Behavioral observations were made on males paired with either ovariectomized or estrous females during a 6-h time period. Most striking was the observation that durations of physical contact were doubled in pairs containing OT-infused males, even in the absence of sexual interactions. Also, OT-infused males showed significantly higher levels of anogenital sniffing of females and autogrooming; however, sexual interactions were unaffected by chronic OT. Chronic OT had no effect on body temperature, analgesia, or exploratory behavior in an open field. These findings suggest that chronic OT in male rats has behavioral effects that may significantly enhance adult social (nonsexual) interactions, possibly through alterations in olfactory and somatosensory information processing. RP WITT, DM (reprint author), NIMH,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 29 TC 155 Z9 156 U1 2 U2 13 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 NOV PY 1992 VL 43 IS 3 BP 855 EP 861 DI 10.1016/0091-3057(92)90418-F PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JW334 UT WOS:A1992JW33400027 PM 1448480 ER PT J AU DUNN, BB CHANNING, MA KIESEWETTER, DO AF DUNN, BB CHANNING, MA KIESEWETTER, DO TI USP STANDARDS FOR C-11 LABELED CARBON-MONOXIDE SO PHARMACOPEIAL FORUM LA English DT Article ID CEREBRAL BLOOD-VOLUME RP DUNN, BB (reprint author), US PHS,NIH,BLDG 10,ROOM 1C-401,BETHESDA,MD 20205, USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU US PHARMACOPEIAL CONVENTION PI ROCKVILLE PA 12601 TWINBROOK PKWY, ROCKVILLE, MD 20852 SN 0363-4655 J9 PHARMACOPEIAL FORUM JI Pharmacop. Forum PD NOV-DEC PY 1992 VL 18 IS 6 BP 4414 EP 4415 PG 2 WC Medicine, Legal; Pharmacology & Pharmacy SC Legal Medicine; Pharmacology & Pharmacy GA JY909 UT WOS:A1992JY90900008 ER PT J AU MUSIAL, F CROWELL, MD FRENCH, AW GUIV, N AF MUSIAL, F CROWELL, MD FRENCH, AW GUIV, N TI EFFECT OF PROLONGED, CONTINUOUS RECTAL DISTENSION ON MOUTH-TO-CECUM AND COLONIC TRANSIT-TIME IN PIGS SO PHYSIOLOGY & BEHAVIOR LA English DT Note DE RECTAL DISTENSION; PIG MOUTH-TO-CECUM TRANSIT TIME; COLONIC TRANSIT TIME ID YUCATAN MINIATURE PIG; CONSTIPATION; DISTENSION; INTESTINE; MOTILITY AB The effect of prolonged (6 h), continuous rectal distention on mouth-to-cecum and colonic transit time was studied in four unrestrained pigs. Mouth-to-cecum transit time was determined from samples of cecal efflux using the phenol red dye technique. Colonic transit time was assessed with radiopaque markers that were injected into the cecum before each trial. Rectal distention was applied 2-1/2 h before feeding, during feeding, and 3-1/2 h after feeding. No distention was applied during control conditions. Stools were collected for 48 h after marker application. Rectal distention increased mouth-to-cecum transit time (p < 0.05). Colonic transit time was also prolonged by rectal distention as shown by a significant decrease in the number of markers excreted within 36 h (p < 0.05). Rectal distention for 6 h increased colonic transit time up to 30 h following distention and prolonged mouth-to-cecum transit of a high fat liquid meal. C1 FRANCIS SCOTT KEY MED CTR,DIV DIGEST DIS,4940 EASTERN AVE,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21218. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 16 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD NOV PY 1992 VL 52 IS 5 BP 1021 EP 1024 DI 10.1016/0031-9384(92)90385-F PG 4 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA JZ482 UT WOS:A1992JZ48200028 PM 1484833 ER PT J AU HEARING, VJ TSUKAMOTO, K URABE, K KAMEYAMA, K MONTAGUE, PM JACKSON, IJ AF HEARING, VJ TSUKAMOTO, K URABE, K KAMEYAMA, K MONTAGUE, PM JACKSON, IJ TI FUNCTIONAL-PROPERTIES OF CLONED MELANOGENIC PROTEINS SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT SYMP ON MOLECULAR BIOLOGY OF PIGMENT CELLS CY NOV 08-09, 1990 CL SENDAI, JAPAN SP TOHOKU UNIV, FAC SCI, POLA LABS DE DOPACHROME TAUTOMERASE; MELANOGENESIS; PIGMENTATION; TYROSINASE ID COAT COLOR LOCUS; MAMMALIAN TYROSINASE; OCULOCUTANEOUS ALBINISM; DOPACHROME CONVERSION; MOUSE TYROSINASE; GENE; CDNA; PIGMENTATION; BIOSYNTHESIS; EXPRESSION AB Several genes critical to the regulation of melanin production in mammals have recently been cloned and characterized. They map to the albino, brown, and slaty loci in mice, and encode proteins with similar structures and features, but with distinct catalytic capacities. The albino locus encodes tyrosinase, an enzyme with three distinct catalytic activities-tyrosine hydroxylase, 3,4-dihydroxyphenylalanine (DOPA) oxidase and DHI (5,6-dihydroxyindole) oxidase. The brown locus encodes TRP-1 (tyrosinase-related protein-1), which has the same, but greatly reduced, catalytic potential. The slaty locus encodes TRP-2, another tyrosinase related-protein, which has DOPAchrome tautomerase activity. In this study we have examined the enzymatic interactions of these proteins, and their regulation by a novel melanogenic inhibitor. We observed that tyrosinase activity is more stable in the presence of TRP-1 and/or TRP-2, but that the catalytic function of TRP-2 is not affected by the presence of TRP-1 or tyrosinase. Other factors also may influence melanogenesis and a unique melanogenic inhibitor suppresses tyrosinase and DOPAchrome tautomerase activities, but does not affect the spontaneous rate of DOPAchrome decarboxylation to DHI. The results demonstrate the catalytic functions of these proteins and how they stably interact within a melanogenic complex in the melanosome to regulate the quantity and quality of melanin synthesized by the melanocyte. C1 KITASATO UNIV,SCH MED,DEPT DERMATOL,KANAGAWA,JAPAN. YAMANASHI MED COLL,DEPT DERMATOL,YAMANASHI,JAPAN. KYUSHU UNIV,DEPT DERMATOL,FUKUOKA 812,JAPAN. WESTERN GEN HOSP,MRC,HUMAN GENET UNIT,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND. RP HEARING, VJ (reprint author), NCI,CELL BIOL LAB,BLDG 37,ROOM 1B22,BETHESDA,MD 20892, USA. NR 47 TC 42 Z9 43 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD NOV PY 1992 VL 5 IS 5 BP 264 EP 270 DI 10.1111/j.1600-0749.1992.tb00547.x PN 2 PG 7 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA KD242 UT WOS:A1992KD24200001 PM 1292007 ER PT J AU FREW, T WHITAKER, B SALTER, D PAYNE, W HUGHES, S YAMAMOTO, H TAKEUCHI, T BRUMBAUGH, J AF FREW, T WHITAKER, B SALTER, D PAYNE, W HUGHES, S YAMAMOTO, H TAKEUCHI, T BRUMBAUGH, J TI THE EXPRESSION OF MOUSE TYROSINASE IN CHICK-CELLS INVITRO AND INVIVO WHEN CONTROLLED BY A CONSTITUTIVE PROMOTER SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT SYMP ON MOLECULAR BIOLOGY OF PIGMENT CELLS CY NOV 08-09, 1990 CL SENDAI, JAPAN SP TOHOKU UNIV, FAC SCI, POLA LABS DE CHICKEN; RETROVIRUS; PIGMENTATION; HEPATOCYTES; FIBROBLASTS; LIVER; DOWN COLORATION ID GERM LINE; MICE; GENE; PHENOTYPE; INSERTION AB Virally introduced mouse tyrosinase expression was checked both in vitro and in vivo in chicken cells and tissues. The results indicate that a constitutive promoter is able to express mouse tyrosinase in a variety of cells and tissues both in vitro and in vivo. Tyrosinase expression is marked by pigment production in situ, which is visible at macroscopic as well as microscopic levels without the use of substrates. It is concluded that tyrosinase can be a valuable marker for tracking gene insertion since it is spontaneously expressed. The expression of tyrosinase in some celts and tissues has a detrimental effect, however, and should be controlled by tissue-specific promoters. C1 UNIV NEBRASKA,SCH BIOL SCI,348 MANTER HALL,LINCOLN,NE 68588. FREDERICK CANC RES FACIL,FREDERICK,MD 21701. MICHIGAN STATE UNIV,DEPT MICROBIOL,E LANSING,MI 48824. AVIAN DIS & ONCOL LAB,E LANSING,MI. TOHOKU UNIV,FAC SCI,INST BIOL,SENDAI,MIYAGI 980,JAPAN. RP BRUMBAUGH, J (reprint author), UNIV NEBRASKA,SCH BIOL SCI,348 MANTER HALL,LINCOLN,NE 68588, USA. FU NCI NIH HHS [N01-CO-74101] NR 21 TC 4 Z9 4 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD NOV PY 1992 VL 5 IS 5 BP 312 EP 321 DI 10.1111/j.1600-0749.1992.tb00555.x PN 2 PG 10 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA KD242 UT WOS:A1992KD24200009 PM 1292014 ER PT J AU CHIEN, DY CHOO, QL TABRIZI, A KUO, C MCFARLAND, J BERGER, K LEE, C SHUSTER, JR NGUYEN, T MOYER, DL TONG, M FURUTA, S OMATA, M TEGTMEIER, G ALTER, H SCHIFF, E JEFFERS, L HOUGHTON, M KUO, G AF CHIEN, DY CHOO, QL TABRIZI, A KUO, C MCFARLAND, J BERGER, K LEE, C SHUSTER, JR NGUYEN, T MOYER, DL TONG, M FURUTA, S OMATA, M TEGTMEIER, G ALTER, H SCHIFF, E JEFFERS, L HOUGHTON, M KUO, G TI DIAGNOSIS OF HEPATITIS-C VIRUS (HCV) INFECTION USING AN IMMUNODOMINANT CHIMERIC POLYPROTEIN TO CAPTURE CIRCULATING ANTIBODIES - REEVALUATION OF THE ROLE OF HCV IN LIVER-DISEASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NON-A, NON-B HEPATITIS; ENZYME IMMUNOASSAY; ENZYME-LINKED IMMUNOSORBENT ASSAY; BLOOD SCREENING ID NON-B-HEPATITIS; BACULOVIRUS EXPRESSION VECTOR; NON-A-HEPATITIS; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; AMERICAN PATIENTS; POST-TRANSFUSION; VIRAL-HEPATITIS; HUMAN CARRIERS; INSECT CELLS AB Structural and nonstructural regions of the HCV-encoded polyprotein have been expressed in recombinant yeast, bacteria, or insect cells and used to capture and measure reactive antibodies circulating in different individuals. The putative nucleocapsid protein (C) and nonstructural proteins 3-5 (NS3-NS5) were found to contain the most immunodominant epitopes. The NS3, NS4, and C regions were expressed in yeast in the form of a fused, chimeric polyprotein (C25) and a capture assay for reactive antibody was developed. This anti-C25 assay detects all previously identified HCV-seropositive cases and provides a substantially more sensitive diagnostic for both acute and chronic HCV infections than the current anti-C100-3 (NS4) assay. Anti-C25 was detected more frequently than anti-C100-3 in chronic, transfusion-associated non-A, non-B hepatitis patients from the United States (95% vs. 71%) and Japan (98% vs. 82%), in cryptogenic cirrhosis patients from the United States (62% vs. 28%), and in hepatitis B surface antigen-negative cases of hepatocellular carcinoma from Japan (83% vs. 63%). These data indicate that HCV has a greater role in these liver diseases than was previously thought. In volunteer United States blood donors sampled following the introduction of anti-C100-3 screening, the prevalence of anti-C25 and anti-C100-3 was 0.5% and 0.08%, respectively. C1 HUNTINGTON MEM HOSP,CTR LIVER,PASADENA,CA 91105. COMMUNITY BLOOD CTR,KANSAS CITY,MO 64111. SHINSHU UNIV,SCH MED,MATSUMOTO,NAGANO 390,JAPAN. CHIBA UNIV,SCH MED,CHIBA,JAPAN. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. UNIV MIAMI,SCH MED,CTR LIVER DIS,DIV HEPATOL,MIAMI,FL 33101. RP CHIEN, DY (reprint author), CHIRON CORP,4560 HORTON ST,EMERYVILLE,CA 94608, USA. NR 36 TC 116 Z9 130 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10011 EP 10015 DI 10.1073/pnas.89.21.10011 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800008 PM 1279666 ER PT J AU CHANCE, MR SAGI, I WIRT, MD FRISBIE, SM SCHEURING, E CHEN, E BESS, JW HENDERSON, LE ARTHUR, LO SOUTH, TL PEREZALVARADO, G SUMMERS, MF AF CHANCE, MR SAGI, I WIRT, MD FRISBIE, SM SCHEURING, E CHEN, E BESS, JW HENDERSON, LE ARTHUR, LO SOUTH, TL PEREZALVARADO, G SUMMERS, MF TI EXTENDED X-RAY ABSORPTION FINE-STRUCTURE STUDIES OF A RETROVIRUS - EQUINE INFECTIOUS-ANEMIA VIRUS CYSTEINE ARRAYS ARE COORDINATED TO ZINC SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MURINE LEUKEMIA-VIRUS; ACID BINDING-PROTEIN; NUCLEOCAPSID PROTEIN; METAL-IONS; SEQUENCE; PEPTIDE; MUTANTS; DOMAIN; EXAFS; SPECTROSCOPY AB Zinc finger arrays have been established as a critical structural feature of proteins involved in DNA recognition. Retroviral nucleocapsid proteins, which are involved in the binding of viral RNA, contain conserved cysteine-rich arrays that have been suggested to coordinate zinc. We provide metalloprotein structural data from an intact virus preparation that validate this hypothesis. Extended x-ray absorption fine structure (EXAFS) spectroscopy of well-characterized and active preparations of equine infectious anemia virus, compared with a peptide with known coordination and in combination with available biochemical and genetic data, defines a Cys3His1 coordination environment for zinc. The average of the Zn-S distances is 2.30(1) angstrom and that of the Zn-N distance (to histidine) is 2.01(3) angstrom. C1 GEORGETOWN UNIV, DEPT CHEM, WASHINGTON, DC 20057 USA. NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYN CORP, FREDERICK, MD 21701 USA. UNIV MARYLAND, DEPT CHEM & BIOCHEM, CATONSVILLE, MD 21228 USA. RP CHANCE, MR (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT PHYSIOL & BIOPHYS, 1300 MORRIS PK AVE, BRONX, NY 10461 USA. RI Bess, Jr., Julian/B-5343-2012 NR 31 TC 51 Z9 51 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10041 EP 10045 DI 10.1073/pnas.89.21.10041 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800014 PM 1332027 ER PT J AU DAVIS, MD RIBEIRO, P TIPPER, J KAUFMAN, S AF DAVIS, MD RIBEIRO, P TIPPER, J KAUFMAN, S TI 7-TETRAHYDROBIOPTERIN, A NATURALLY-OCCURRING ANALOG OF TETRAHYDROBIOPTERIN, IS A COFACTOR FOR AND A POTENTIAL INHIBITOR OF THE AROMATIC AMINO-ACID HYDROXYLASES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 2-AMINO-4-HYDROXY-7-[DIHYDROXYLPROPYL-(L-ERYTHRO)-5,6,7,8-TETRAHYDROPTER IN] ID LIVER PHENYLALANINE-HYDROXYLASE; TYROSINE-HYDROXYLASE; RAT-LIVER; PARTIAL PURIFICATION; PHENYLKETONURIA; STIMULATION; ACTIVATION; OXIDATION; PROTEIN; ENZYME AB The ability of 2-amino-4-hydroxy-7-[dihydroxylpropyl-(L-erythro)-5,6,7,8-tetrahydropterin] ("7-tetrahydrobiopterin" or 7-BH4) to substitute for the natural cofactor tetrahydrobiopterin (BH4) has been studied in vitro in the reactions of the three mammalian aromatic amino acid hydroxylases. With rat liver phenylalanine hydroxylase, the apparent K(m) for 7-BH4 is 160 muM, a value that is almost-equal-to 60-fold greater than that for the natural cofactor. In contrast, the hydroxylase reaction is severely inhibited by as little as 1 muM 7-BH4 when assayed in the presence of physiological concentrations of BH4. This inhibition can be overcome either by an increase in the concentration of BH4 or a decrease in the concentration of phenylalanine. With both rat brain tryptophan hydroxylase and rat pheochromocytoma tyrosine hydroxylase, the K(m) value for 7-BH4 is about one order of magnitude greater than the K(m) for BH4. Accordingly, 7-BH4 is a poor competitive inhibitor of both tryptophan and tyrosine hydroxylase. Thus, our results suggest that the observed hyperphenylalaninemia in patients who excrete 7-BH4 in their urine may arise directly from the inhibition of phenylalanine hydroxylase by low levels of this pterin. On the other hand, it is less likely that low levels of 7-BH4 would affect the activity of tyrosine or tryptophan hydroxylase in vivo. RP DAVIS, MD (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 34 TC 46 Z9 46 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10109 EP 10113 DI 10.1073/pnas.89.21.10109 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800028 PM 1359535 ER PT J AU LEVINE, A CANTONI, GL RAZIN, A AF LEVINE, A CANTONI, GL RAZIN, A TI METHYLATION IN THE PREINITIATION DOMAIN SUPPRESSES GENE-TRANSCRIPTION BY AN INDIRECT MECHANISM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSIENT TRANSFECTIONS; TRANSCRIPTION FACTOR TFIID AND TFIIA BINDING; INVITRO TRANSCRIPTION; TRANSCRIPTION REINITIATION ID DNA METHYLATION; CHROMATIN STRUCTURE; CPG METHYLATION; PROMOTER; EXPRESSION; BINDING; PROTEIN AB Although the first observations of the inhibitory effect of methylation on gene activity were made almost a decade ago, the mechanism by which methyl groups affect transcription is still obscure. Here we use engineered promoters methylated in vitro in transient transfections to study the mechanism by which methylation mediates promoter repression. The results clearly show that the location of the methyl groups within the promoter region determines the extent of promoter repression. The most effective suppression was observed when methylation was in the preinitiation domain. The results also support a previous suggestion that a mediator protein is involved in the mechanism of promoter inhibition. The suppressor effect of methylation at sequences flanking the TATA box can be partially overcome in the presence of the simian virus 40 enhancer. In addition, results obtained by transient thymidine labeling of Ltk- cells that were transfected with a methylated thymidine kinase gene from herpes simplex virus, at the level of approximately one template per cell, further support the conclusion that methylation affects primarily transcription preinitiation. C1 NIMH,GEN & COMPARAT BIOCHEM LAB,BETHESDA,MD 20892. RP LEVINE, A (reprint author), HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT CELLULAR BIOL,IL-91010 JERUSALEM,ISRAEL. FU NIGMS NIH HHS [GM 20483] NR 24 TC 52 Z9 52 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10119 EP 10123 DI 10.1073/pnas.89.21.10119 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800030 PM 1332030 ER PT J AU NAKASU, S TOMIZAWA, J AF NAKASU, S TOMIZAWA, J TI STRUCTURE OF THE COLE1 DNA MOLECULE BEFORE SEGREGATION TO DAUGHTER MOLECULES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE COLE1 PLASMID; DNA REPLICATION; CATENANE ID E1 PLASMID DNA; INTERTWINED CATENATED DIMERS; ESCHERICHIA-COLI; CELL-EXTRACTS; CHROMOSOME SEGREGATION; RIBONUCLEASE-H; REPLICATION; TOPOISOMERASES; TERMINATION; ORIGIN AB The segregation of daughter DNA molecules at the end stage of replication of plasmid ColE1 was examined. When circular ColE1 DNA replicates in a cell extract at a high KCl concentration (140 mM), a unique class of molecules accumulates. When the molecule is cleaved by a restriction enzyme that cuts the ColE1 DNA at a single site, an X-shaped molecule in which two linear components are held together around the origin of DNA replication is made. For a large fraction of these molecules, the 5' end of the leading strand remains at the origin and the 3' end of the strand is about 30 nucleotides upstream of the origin. The 3' end of the lagging strand is located at the terH site (17 nucleotides upstream of the origin) and the 5' end of the strand is a few hundred nucleotides upstream of the terH site. Thus the parental strands of the molecule intertwine with each other only once. When the KCl concentration is lowered to 70 mM, practically all of these molecules are converted to daughter circular monomers or to catenanes consisting of two singly interlocked circular units. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 27 TC 7 Z9 7 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10139 EP 10143 DI 10.1073/pnas.89.21.10139 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800034 PM 1438203 ER PT J AU BARBAS, CF CROWE, JE CABABA, D JONES, TM ZEBEDEE, SL MURPHY, BR CHANOCK, RM BURTON, DR AF BARBAS, CF CROWE, JE CABABA, D JONES, TM ZEBEDEE, SL MURPHY, BR CHANOCK, RM BURTON, DR TI HUMAN MONOCLONAL FAB FRAGMENTS DERIVED FROM A COMBINATORIAL LIBRARY BIND TO RESPIRATORY SYNCYTIAL VIRUS-F GLYCOPROTEIN AND NEUTRALIZE INFECTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIBODY REPERTOIRES; PASSIVE IMMUNIZATION; FILAMENTOUS PHAGE; PHAGE SURFACE EXPRESSION ID COTTON RATS; ANTIBODIES; IMMUNOTHERAPY AB Respiratory syncytial virus (RSV) is the most important cause, throughout the world, of severe viral lower respiratory tract illness in young children. Antibodies are known to mediate resistance to RSV infection and illness. We have isolated a number of human monoclonal Fab fragments to RSV F glycoprotein from a combinatorial antibody library expressed on the surface of phage. One of these neutralized a wide range of virus isolates, 10 subgroup A and 9 subgroup B isolates, with a titer (60 % neutralization) of almost-equal-to 0.1-1.0 mug/ml. Another Fab neutralized diverse isolates at a concentration somewhat higher. These human Fab fragments show great promise for use in the prophylaxis or therapy of serious RSV lower respiratory tract disease. For intramuscular or intravenous administration, whole antibodies will be required, whereas for aerosol application, F(ab')2 or Fab fragments may suffice. C1 RW JOHNSON PHARMACEUT RES INST, SAN DIEGO, CA 92121 USA. NIAID, INFECT DIS LAB, BETHESDA, MD 20892 USA. SCRIPPS RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. RP BARBAS, CF (reprint author), SCRIPPS RES INST, DEPT IMMUNOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 21 TC 161 Z9 165 U1 6 U2 8 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10164 EP 10168 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800039 PM 1279672 ER PT J AU CHANOCK, SJ FAUST, LP BARRETT, D BIZAL, C MALY, FE NEWBURGER, PE RUEDI, JM SMITH, RM BABIOR, BM AF CHANOCK, SJ FAUST, LP BARRETT, D BIZAL, C MALY, FE NEWBURGER, PE RUEDI, JM SMITH, RM BABIOR, BM TI O2(-) PRODUCTION BY LYMPHOCYTES-B LACKING THE RESPIRATORY BURST OXIDASE SUBUNIT P47PHOX AFTER TRANSFECTION WITH AN EXPRESSION VECTOR CONTAINING A P47PHOX CDNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; CELL-FREE SYSTEM; ADENINE-DINUCLEOTIDE PHOSPHATE; NEUTROPHIL CYTOCHROME-B; 2 CYTOSOLIC COMPONENTS; NADPH OXIDASE; POLYMORPHONUCLEAR LEUKOCYTES; SUPEROXIDE GENERATION; PLASMA-MEMBRANE; ACTIVATION AB The respiratory burst oxidase of phagocytes and B lymphocytes is a complicated enzyme that catalyzes the one-electron reduction of oxygen by NADPH. It is responsible for the O2- production that occurs when these cells are exposed to phorbol 12-myristate 13-acetate or other appropriate stimuli. The activity of this enzyme is greatly decreased or absent in patients with chronic granulomatous disease, an inherited disorder characterized by a severe defect in host defense against bacteria and fungi. In every chronic granulomatous disease patient studied to date, an abnormality has been found in a gene encoding one of four components of the respiratory burst oxidase: the membrane protein p22phox or gp91phox, or the cytosolic protein p47phox or p67phox. We report here that O2- production was partly restored to phorbol 12-myristate 13-acetate-stimulated Epstein-Barr virus-transformed B lymphocytes from a patient with p47phox-deficient chronic granulomatous disease by transfection with an expression plasmid containing a p47phox cDNA inserted in the sense direction. No detectable O2- was produced by untransfected p47phox-deficient lymphocytes or by p47phox-deficient lymphocytes transfected with an antisense plasmid. The finding that O2- can be produced by p47phox-deficient B lymphocytes after the transfer of a p47phox cDNA into the deficient cells suggests that this system could be useful for studying the function of mutant p47phox proteins in whole cells. C1 UNIV MASSACHUSETTS, SCH MED, DEPT PEDIAT, WORCESTER, MA 01655 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. UNIV CALIF SAN DIEGO, SCH MED, DEPT MED, LA JOLLA, CA 92093 USA. CHILDRENS HOSP MED CTR, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. NCI, PEDIAT BRANCH, FREDERICK, MD 21701 USA. RP CHANOCK, SJ (reprint author), SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. FU NIAID NIH HHS [AI-24838, AI-24227, AI-28479] NR 40 TC 46 Z9 46 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10174 EP 10177 DI 10.1073/pnas.89.21.10174 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800041 PM 1332032 ER PT J AU KLIMPEL, KR MOLLOY, SS THOMAS, G LEPPLA, SH AF KLIMPEL, KR MOLLOY, SS THOMAS, G LEPPLA, SH TI ANTHRAX TOXIN PROTECTIVE ANTIGEN IS ACTIVATED BY A CELL-SURFACE PROTEASE WITH THE SEQUENCE SPECIFICITY AND CATALYTIC PROPERTIES OF FURIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BACILLUS-ANTHRACIS; PROTEIN PROCESSING; PAIRED BASIC RESIDUES; MUTAGENESIS; CONSENSUS SEQUENCE ID BACILLUS-ANTHRACIS; LETHAL TOXIN; DIPHTHERIA-TOXIN; LOW-PH; CLEAVAGE; CYCLASE; INVIVO AB Proteolytic cleavage of the protective antigen (PA) protein of anthrax toxin at residues 164-167 is necessary for toxic activity. Cleavage by a cellular protease at this sequence, Arg-Lys-Lys-Arg, normally follows binding of PA to a cell surface receptor. We attempted to identify this protease by determining its sequence specificity and catalytic properties. Semi-random cassette mutagenesis was used to generate mutants with replacements of residues 164-167 by Arg, Lys, Ser, or Asn. Analysis of 19 mutant proteins suggested that lethal factor-dependent toxicity required the sequence Arg-Xaa-Xaa-Arg. Based on these data, three additional mutants were constructed with the sequences Ala-Lys-Lys-Arg, Arg-Lys-Lys-Ala, and Arg-Ala-Ala-Arg. Of these mutant proteins, Arg-Ala-Ala-Arg was toxic, confirming that the cellular protease can recognize the sequence Arg-Xaa-Xaa-Arg. The mutant containing the sequence Ala-Lys-Lys-Arg was also toxic but required >13 times more protein to produce equivalent toxicity. This sequence specificity is similar to that of the ubiquitous subtilisin-like protease furin, which is involved in processing of precursors of certain receptors and growth factors. Therefore we tested whether a recombinant soluble furin would cleave PA. This furin derivative efficiently cleaved native PA and the Arg-Ala-Ala-Arg mutant but not the non-toxic PA mutants. In addition, previously identified inhibitors of furin blocked cleavage of receptor-bound PA. These data imply that furin is the cellular protease that activates PA, and that nearly all cell types contain at least a small amount of furin exposed on their cell surface. C1 NIDR, MICROBIAL ECOL LAB, BLDG 30, RM 309, BETHESDA, MD 20892 USA. OREGON HLTH SCI UNIV, VOLLUM INST, PORTLAND, OR 97201 USA. FU NIDDK NIH HHS [DK08703, DK37274, DK44629] NR 29 TC 353 Z9 362 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10277 EP 10281 DI 10.1073/pnas.89.21.10277 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800062 PM 1438214 ER PT J AU O'SHEA, JJ MCVICAR, DW BAILEY, TL BURNS, C SMYTH, MJ AF O'SHEA, JJ MCVICAR, DW BAILEY, TL BURNS, C SMYTH, MJ TI ACTIVATION OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES-T BY PHARMACOLOGICAL INDUCTION OF PROTEIN-TYROSINE PHOSPHORYLATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CALCIUM; INTERLEUKIN-2; CD28 ID CELL ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; MEDIATED SIGNAL TRANSDUCTION; PHOSPHOLIPASE-C; INTERLEUKIN-2 PRODUCTION; COSTIMULATORY SIGNAL; PHOSPHATASE CD45; FC-RECEPTOR; KINASE; PROLIFERATION AB Protein-tyrosine kinase and protein-tyrosine phosphatase (PTPase) activities are essential for T-cell antigen receptor-mediated signaling. To assess the functional consequences of alteration of the levels of tyrosine phosphorylation in normal human T cells, the effects of vanadate and hydrogen peroxide were studied. In combination, these agents induced tyrosine phosphorylation of cellular substrates, elevated cytosolic free calcium, and induced interleukin 2 receptor (IL-2R) alpha chain expression but not IL-2 secretion. However, anti-CD28 antibody in combination with vanadate and hydrogen peroxide induced IL-2 secretion, consistent with the requirement for a costimulatory signal in the induction of this gene. The effects of vanadate and hydrogen peroxide were enhanced in the absence of the T-cell PTPase, CD45. Thus, acute pharmacologic manipulation of the level of tyrosine phosphorylation in normal T cells correlates with partial, but not full, activation of these cells; in concert with a costimulatory signal provided by perturbation of the CD28 molecule, the complete program of activation is initiated. These agents should prove useful in dissecting signaling pathways involved in the regulation of genes critical to the immune response. C1 NCI, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC, DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. RP O'SHEA, JJ (reprint author), NCI, EXPTL IMMUNOL LAB, LEUKOCYTE CELL BIOL SECT, FREDERICK, MD 21702 USA. RI McVicar, Daniel/G-1970-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU NCI NIH HHS [N01-CO-74102] NR 42 TC 161 Z9 161 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10306 EP 10310 DI 10.1073/pnas.89.21.10306 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800068 PM 1279675 ER PT J AU WICKNER, S SKOWYRA, D HOSKINS, J MCKENNEY, K AF WICKNER, S SKOWYRA, D HOSKINS, J MCKENNEY, K TI DNAJ, DNAK, AND GRPE HEAT-SHOCK PROTEINS ARE REQUIRED IN ORIP1 DNA-REPLICATION SOLELY AT THE REPA MONOMERIZATION STEP SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SPECIALIZED NUCLEOPROTEIN STRUCTURES; F PLASMID REPLICATION; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; ORIGIN; INITIATION; GENE; BINDING; P1; TEMPERATURES AB We have found that three Escherichia coli heat shock proteins, DnaK (the hsp70 homolog), Dnaj, and GrpE, function in oriP1 DNA replication in vitro solely to activate DNA binding by the replication initiator protein RepA. Activation results from the conversion of P1 or P7 RepA dimers to monomers that bind with high affinity to the origin of replication of plasmid P1. Thus, the essential role of these three heat shock proteins in this replication system is to change the quaternary structure of a single protein, RepA. C1 NATL INST STAND & TECHNOL,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. RP WICKNER, S (reprint author), NCI,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 30 TC 71 Z9 71 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10345 EP 10349 DI 10.1073/pnas.89.21.10345 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800076 PM 1438220 ER PT J AU GROSSMAN, Z PAUL, WE AF GROSSMAN, Z PAUL, WE TI ADAPTIVE CELLULAR INTERACTIONS IN THE IMMUNE-SYSTEM - THE TUNABLE ACTIVATION THRESHOLD AND THE SIGNIFICANCE OF SUBTHRESHOLD RESPONSES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CONTEXT DISCRIMINATION; AUTOREACTIVITY; ANERGY; MEMORY UNITS ID T-CELLS; TRANSGENIC MICE; SPECIFICITY; SELECTION; TOLERANCE; SELF; DEFICIENT; MOLECULES AB A major challenge for immunologists is to explain how the immune system adjusts its responses to the microenvironmental context in which antigens are recognized. We propose that lymphocytes achieve this by tuning and updating their responsiveness to recurrent signals. In particular, cellular anergy in vivo is a dynamic state in which the threshold for a stereotypic mode of activation has been elevated. Anergy is associated with other forms of cellular activity, not paralysis. Cells engaged in such subthreshold interactions mediate functions such as maintenance of immunological memory and control of infections. In such interactions, patterns of signals are recognized and classified and evoke selective responses. The robust mechanism proposed for segregation of suprathreshold and subthreshold immune responses allows lymphocytes to use recognition of self-antigens in executing physiological functions. Autoreactivity is allowed where it is dissociated from uncontrolled aggression. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP GROSSMAN, Z (reprint author), TEL AVIV UNIV,SACKLER FAC MED,DEPT PHYSIOL & PHARMACOL,IL-69978 TEL AVIV,ISRAEL. RI Grossman, Zvi/A-9643-2008 NR 30 TC 160 Z9 162 U1 0 U2 6 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10365 EP 10369 DI 10.1073/pnas.89.21.10365 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800080 PM 1438221 ER PT J AU LESNIK, P ROUIS, M SKARLATOS, S KRUTH, HS CHAPMAN, MJ AF LESNIK, P ROUIS, M SKARLATOS, S KRUTH, HS CHAPMAN, MJ TI UPTAKE OF EXOGENOUS FREE-CHOLESTEROL INDUCES UP-REGULATION OF TISSUE FACTOR EXPRESSION IN HUMAN MONOCYTE-DERIVED MACROPHAGES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE THROMBOSIS; ATHEROSCLEROSIS ID LOW-DENSITY-LIPOPROTEIN; PROCOAGULANT ACTIVITY INVITRO; HUMAN-PLASMA; CELLS; INDUCTION; SUPPRESSION; GENERATION; ACTIVATION AB Lipid-laden macrophages present as foam cells may contribute to the hyperthrombotic state of human atherosclerotic lesions by the production of tissue factor (TF). We investigated the effect of exogenous nonlipoprotein cholesterol on the expression of TF by human monocyte-derived macrophages in culture. Nonlipoprotein cholesterol at 50 mug/ml increased TF activity 4-fold; TF induction was dose- and time-dependent. Expression of TF activity was positively correlated with the free cholesterol content of monocyte-derived macrophages, was increased upon inhibition of cholesterol esterification, and reflected de novo synthesis of TF protein. TF expression in cholesterol-loaded macrophages remained sensitive to stimulation (almost-equal-to 12-fold) by bacterial lipopolysaccharide, indicating that intracellular free cholesterol and lipopolysaccharide act by distinct mechanisms in inducing TF procoagulant activity. Our results suggest that loading human monocyte-derived macrophages with free cholesterol induces upregulation of TF expression, thereby contributing to thrombus formation at sites of plaque rupture. C1 NHLBI,EXPTL ATHEROSCLEROSIS SECT,BETHESDA,MD 20892. RP LESNIK, P (reprint author), HOP PITIE,INSERM,U321,UNITE RECH LIPOPROT & ATHEROGENESE,F-75651 PARIS 13,FRANCE. RI Rouis, Mustapha/E-4993-2016; Lesnik, Philippe/F-7803-2011 NR 26 TC 76 Z9 80 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10370 EP 10374 DI 10.1073/pnas.89.21.10370 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800081 PM 1438222 ER PT J AU MINTON, AP COLCLASURE, GC PARKER, JC AF MINTON, AP COLCLASURE, GC PARKER, JC TI MODEL FOR THE ROLE OF MACROMOLECULAR CROWDING IN REGULATION OF CELLULAR-VOLUME SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SWELLING-ACTIVATED ION TRANSPORTERS; EXCLUDED VOLUME; SCALED PARTICLE THEORY ID DOG RED-CELLS; KCL COTRANSPORT; EXCLUDED VOLUME; OKADAIC ACID; ACTIVATION; DEPHOSPHORYLATION; INHIBITION; CYTOPLASM; TRANSPORT; PROTEINS AB A simple model is proposed to account for large increases in transporter-mediated ion flux across cell membranes that are elicited by small fractional changes of cell volume. The model is based upon the concept that, as a result of large excluded volume effects in cytoplasm (macromolecular crowding), the tendency of soluble macromolecules to associate with membrane proteins is much more sensitive to changes in cell water content than expected on the basis of simple considerations of mass action. The model postulates that an ion transporter may exist in either an active dephosphorylated state or an inactive phosphorylated state and that the steady-state activity of the transporter reflects a balance between the rates of phosphatase-catalyzed activation and kinase-catalyzed inactivation. Cell swelling results in the inhibition of kinase relative to phosphatase activity, thereby increasing the steady-state concentration of the active form of the transporter. Calculated volume-dependent stimulation of ion flux is comparable to that observed experimentally. C1 UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. RP MINTON, AP (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 20 TC 115 Z9 117 U1 1 U2 10 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10504 EP 10506 DI 10.1073/pnas.89.21.10504 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800108 PM 1332050 ER PT J AU PLETNEV, AG BRAY, M HUGGINS, J LAI, CJ AF PLETNEV, AG BRAY, M HUGGINS, J LAI, CJ TI CONSTRUCTION AND CHARACTERIZATION OF CHIMERIC TICK-BORNE ENCEPHALITIS DENGUE TYPE-4 VIRUSES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DENGUE VIRUS; TICK-BORNE ENCEPHALITIS VIRUS; VIRAL CHIMERA; NEUROVIRULENCE; PROTECTIVE IMMUNITY ID STRUCTURAL PROTEINS; NONSTRUCTURAL PROTEINS; NUCLEOTIDE-SEQUENCE; MICE; FLAVIVIRUS; GENES; NS1; RNA; IMMUNIZATION; POLYPROTEIN AB Dengue type 4 virus (DEN4) cDNA was used as a vector to express genes of the distantly related tick-borne encephalitis virus (TBEV). Full-length chimerk TBEV/DEN4 cDNAs were constructed by substituting TBEV genes coding for proteins such as capsid (C); pre-membrane, which is the precursor of membrane (M); envelope (E); or nonstructural protein NS1 for the corresponding DEN4 sequences. RNA transcripts prepared from cDNAs were used to transfect permissive simian cells. Two viable chimeric viruses that contained TBEV CME or ME genes were recovered. Compared with DEN4, chimeric TBE(ME)/DEN4 virus [designated vTBE(ME)/DEN4] produced larger plaques and grew to higher titer in simian cells. In contrast, vTBE(ME)/DEN4 produced smaller plaques on mosquito cells and grew to lower titer than DEN4. Analysis of viral RNA and proteins produced in vTBE(ME)/DEN4- and DEN4-infected mosquito or simian cells revealed that the chimera was restricted in its ability to enter and replicate in mosquito cells. In contrast, vTBE(ME)/DEN4 entered simian cells efficiently and its RNA was replicated more rapidly in these cells than was parental DEN4 RNA. Following intracerebral inoculation, vTBE(ME)/DEN4 caused fatal encephalitis in both suckling and adult mice, while nearly all mice inoculated by the same route with DEN4 did not develop disease. Unlike wild-type TBEV, vTBE(ME)/DEN4 did not cause encephalitis when adult mice were inoculated by a peripheral route. Adult mice previously inoculated with the chimera by a peripheral route were completely resistant to subsequent intraperitoneal challenge with 10(3) times the median lethal dose of TBEV, whereas mice previously inoculated with DEN4 were not protected. These findings indicate that (i) the TBEV M and E genes of the chimeric virus are major protective antigens and induce resistance to lethal TBEV challenge and (ii) other regions of the TBEV genome are essential for the ability of this virus to spread from a peripheral site to the brain. Success in constructing a viable TBEV/DEN4 chimera that retains the protective antigens of TBEV but lacks its peripheral invasiveness provides a strategy for the development of live attenuated TBEV vaccines. C1 RUSSIAN ACAD SCI,NOVOSIBIRSK INST BIOORGAN CHEM,NOVOSIBIRSK 630090,USSR. USA,MED RES INST INFECT DIS,FREDERICK,MD 21702. RP PLETNEV, AG (reprint author), NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892, USA. NR 30 TC 104 Z9 108 U1 0 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10532 EP 10536 DI 10.1073/pnas.89.21.10532 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800114 PM 1438242 ER PT J AU BERNEMAN, ZN ABLASHI, DV LI, G EGERFLETCHER, M REITZ, MS HUNG, CL BRUS, I KOMAROFF, AL GALLO, RC AF BERNEMAN, ZN ABLASHI, DV LI, G EGERFLETCHER, M REITZ, MS HUNG, CL BRUS, I KOMAROFF, AL GALLO, RC TI HUMAN HERPESVIRUS-7 IS A T-LYMPHOTROPIC VIRUS AND IS RELATED TO, BUT SIGNIFICANTLY DIFFERENT FROM, HUMAN HERPESVIRUS-6 AND HUMAN CYTOMEGALOVIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHRONIC FATIGUE SYNDROME; LYMPHOCYTES-T ID HHV-6; SEQUENCE; CELLS; DNA; IDENTIFICATION; STRAIN; HBLV; CD4+ AB An independent strain (JI) of human herpesvirus 7 (HHV-7) was isolated from a patient with chronic fatigue syndrome (CFS). No significant association could be established by seroepidemiology between HHV-7 and CFS. HHV-7 is a T-lymphotropic virus, infecting CD4+ and CD8+ primary lymphocytes. HHV-7 can also infect SUP-T1, an immature T-cell line, with variable success. Southern blot analysis with DNA probes scanning 58.8% of the human herpesvirus 6 (HHV-6) genome and hybridizing to all HHV-6 strains tested so far revealed homology to HHV-7 with only 37.4% of the total probe length. HHV-7 contains the GGGTTA repetitive sequence, as do HHV-6 and Marek's disease chicken herpesvirus. DNA sequencing of a 186-base-pair fragment of HHV-7(JI) revealed an identity with HHV-6 and human cytomegalovirus of 57.5% and 36%, respectively. Oligonucleotide primers derived from this sequence (HV7/HV8, HV10/HV11) amplified HHV-7 DNA only and did not amplify DNA from other human herpesviruses, including 12 different HHV-6 strains. Southern blot analysis with the p43L3 probe containing the 186-base-pair HHV-7 DNA fragment hybridized to HHV-7 DNA only. The molecular divergence between human cytomegalovirus, on the one hand, and HHV-6 and HHV-7, on the other, is greater than between HHV-6 and HHV-7, which, in turn, is greater than the difference between HHV-6 strains. This study supports the classification of HHV-7 as an additional member of the human beta-herpesviruses. C1 NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. PHARMACIA,COLUMBIA,MD 21045. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT INTERNAL MED,BOSTON,MA 02115. FU NIAID NIH HHS [R01AI26788, R01AI27314, U01AI32246] NR 30 TC 208 Z9 214 U1 1 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10552 EP 10556 DI 10.1073/pnas.89.21.10552 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800118 PM 1332051 ER PT J AU CALVO, JC CHERNICK, S RODBARD, D AF CALVO, JC CHERNICK, S RODBARD, D TI MOUSE MAMMARY EPITHELIUM PRODUCES A SOLUBLE HEAT-SENSITIVE MACROMOLECULE THAT INHIBITS DIFFERENTIATION OF 3T3-L1 PREADIPOCYTES SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID TUMOR NECROSIS FACTOR; ADIPOCYTE DIFFERENTIATION; CELL-LINE; PROTEOGLYCANS; INTERLEUKIN-1; CULTURE AB Coculture of normal mouse mammary gland (NMMG) epithelial cells with 3T3-L1 preadipocytes resulted in inhibition of triglyceride accumulation. This inhibition was also observed when the NMMG cells were grown in inserts and placed within a 100-mm dish containing confluent 3T3-L1 cells. As the number of NMMG-containing inserts was increased, there was a progressive decline in triglyceride content of the 3T3-L1 cells. Conditioned medium from NMMG cells also resulted in a dose-dependent inhibition of adipocyte formation, and when concentrated 10-fold by passage through a filter with a cutoff of 30 kDa, all of the inhibitory activity was recovered. Heating the concentrated conditioned medium at 98-degrees-C for 30 min resulted in complete loss of activity. Of several peptides tested, transforming growth factor-beta, platelet-derived growth factor, tumor necrosis factor, interleukin 6, and basic fibroblast growth factor showed inhibitory activity, whereas epidermal growth factor, insulin-like growth factor 1, and transforming growth factor-alpha did not. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NR 23 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD NOV PY 1992 VL 201 IS 2 BP 174 EP 179 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JU733 UT WOS:A1992JU73300007 PM 1384065 ER PT J AU COVELL, DG AF COVELL, DG TI FOLDING PROTEIN ALPHA-CARBON CHAINS INTO COMPACT FORMS BY MONTE-CARLO METHODS SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE LATTICE MODELS; FOLDED PROTEINS; COMPACT STATES ID COMPUTER-SIMULATION; GLOBULAR-PROTEIN; TERTIARY STRUCTURE; RANGE INTERACTIONS; PHASE-TRANSITION; LATTICE; MODEL; CONFORMATIONS; DYNAMICS; FLUCTUATIONS AB A method is presented for generating folded chains of specific amino acid sequences on a simple cubic lattice. Monte Carlo simulations are used to transform extended geometries of simplified alpha-carbon chains for eight small monomeric globular proteins into folded states. Permitted chain transitions are limited to a few types of moves, all restricted to occur on the lattice. Crude residue-residue potentials derived from statistical structure data are used to describe the energies for each conformer. The low resolution structures obtained by this procedure contain many of the correct gross features of the native folded architectures with respect to average residue energy per nonbonded contact, segment density, and location of surface loops and disulfide pairs. Rms deviations between these and the native X-ray structures and percentage of native long-range contacts found in these final folded structures are 7.6+/-0.7 angstrom and 48+/-3%, respectively. This procedure can be useful for predicting approximate tertiary interactions from amino acid sequence. RP COVELL, DG (reprint author), DYNCORP INC,NCI,FREDERICK CANC RES & DEV CTR,BLDG 430,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 57 TC 72 Z9 73 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 0887-3585 J9 PROTEINS JI Proteins PD NOV PY 1992 VL 14 IS 3 BP 409 EP 420 DI 10.1002/prot.340140310 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JT616 UT WOS:A1992JT61600009 PM 1438179 ER PT J AU HANS, SL MARCUS, J HENSON, L AUERBACH, JG MIRSKY, AF AF HANS, SL MARCUS, J HENSON, L AUERBACH, JG MIRSKY, AF TI INTERPERSONAL-BEHAVIOR OF CHILDREN AT RISK FOR SCHIZOPHRENIA SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article; Proceedings Paper CT MEETING OF THE SOC FOR LIFE HISTORY RESEARCH IN PSYCHOPATHOLOGY CY OCT, 1990 CL KEYSTONE, CO SP SOC LIFE HIST RES PSYCHOPATHOL ID JERUSALEM INFANT-DEVELOPMENT; ISRAELI HIGH-RISK; SOCIAL COMPETENCE; FOLLOW-UP; INTERVIEW; PSYCHOPATHOLOGY; ANTECEDENTS; CHECKLIST; DISORDERS; SPECTRUM AB INVESTIGATIONS of the childhood antecedents of adult schizophrenia may clarify our understanding of the etiology of the disease, provide guidelines for meaningful classification of subtypes of schizophrenic illness, point to strategies for identifying those individuals in need for early intervention, and suggest appropriate techniques for early intervention. Among the more salient characteristics of schizophrenic illness are disturbances in interpersonal relations, especially withdrawal from normal social interaction. C1 HEBREW UNIV JERUSALEM,DEPT PSYCHOL,JERUSALEM,ISRAEL. NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. RP HANS, SL (reprint author), UNIV CHICAGO,DEPT PSYCHIAT,MC3077,5841 S MARYLAND AVE,CHICAGO,IL 60637, USA. NR 98 TC 33 Z9 33 U1 17 U2 18 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD NOV PY 1992 VL 55 IS 4 BP 314 EP 335 PG 22 WC Psychiatry SC Psychiatry GA KD200 UT WOS:A1992KD20000002 PM 1470672 ER PT J AU ELMALLAKH, RS EGAN, M WYATT, RJ AF ELMALLAKH, RS EGAN, M WYATT, RJ TI CREATINE-KINASE AND ENOLASE - INTRACELLULAR ENZYMES SERVING AS MARKERS OF CENTRAL-NERVOUS-SYSTEM DAMAGE IN NEUROPSYCHIATRIC DISORDERS SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID NEURON-SPECIFIC ENOLASE; GLIA-SPECIFIC PROTEINS; OPEN-HEART SURGERY; CEREBROSPINAL-FLUID; BB-ISOENZYME; HUMAN-BRAIN; IMMUNOHISTOCHEMICAL LOCALIZATION; VENTRICULAR ENLARGEMENT; HUNTINGTONS-DISEASE; NEUROLOGICAL DISORDERS AB A FREQUENTLY used method to assess cellular dysfunction and damage in humans is to document the presence of uniquely intracellular proteins in extracellular spaces. Thus, increased plasma levels of transaminases generally reflect hepatocellular damage (Lieber 1978), increases in the cardiac fractions of creatine kinase (CK, or CPK for creatine phosphokinase) or lactate dehydrogenase (LDH) are diagnostic for myocardial infarction (Armstrong et al. 1979; 1982), and increases of skeletal muscle fractions of CK may indicate myopathy (Goto 1974; Ford 1984). Similarly, a number of enzymes and proteins serve as tumor markers in a variety of malignant cancer (e.g., Concannon et al. 1974; Foti et al. 1977). C1 NEUROPSYCHIAT RES HOSP,NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC. RP ELMALLAKH, RS (reprint author), UNIV LOUISVILLE,DEPT PSYCHIAT,LOUISVILLE,KY 40292, USA. NR 98 TC 10 Z9 10 U1 1 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD NOV PY 1992 VL 55 IS 4 BP 392 EP 402 PG 11 WC Psychiatry SC Psychiatry GA KD200 UT WOS:A1992KD20000007 PM 1470677 ER PT J AU DOUDET, DJ AIGNER, TG MCLELLAN, CA COHEN, RM AF DOUDET, DJ AIGNER, TG MCLELLAN, CA COHEN, RM TI POSITRON EMISSION TOMOGRAPHY WITH F-18 DOPA - INTERPRETATION AND BIOLOGICAL CORRELATES IN NONHUMAN-PRIMATES SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE PARKINSONISM; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP); DOPAMINE; RHESUS MONKEY; UPTAKE RATE CONSTANT; AGING ID BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; PARKINSONS-DISEASE; DOPAMINE-RECEPTORS; RHESUS-MONKEY; GRAPHICAL EVALUATION; PREFRONTAL CORTEX; RAT-BRAIN; MPTP; KINETICS AB Positron emission tomography (PET) was carried out, with F-18-DOPA as a ligand, in normal control monkeys and ''parkinsonian'' monkeys who had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The following approaches were used in data analysis: ratio of F-18 accumulation in specific to nonspecific brain areas and F-18-DOPA influx constant obtained using either the actual plasma F-18-DOPA or the F-18 activity in a nonspecific brain area as the input function. The results from these analyses were compared to one another and to biological parameters relevant to dopaminergic function. The striatum/cortex ratio and the rate constant calculated from plasma F-18-DOPA appeared to be the most sensitive analytic techniques. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP DOUDET, DJ (reprint author), NIMH,CLIN BRAIN IMAGING SECT,CEREBRAL METAB LAB,BLDG 10-4N317,BETHESDA,MD 20892, USA. NR 33 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV PY 1992 VL 45 IS 3 BP 153 EP 168 DI 10.1016/0925-4927(92)90023-W PG 16 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KG096 UT WOS:A1992KG09600002 PM 1283014 ER PT J AU COPPOLA, R MARENCO, S JONES, DW BERMAN, KF WEINBERGER, DR AF COPPOLA, R MARENCO, S JONES, DW BERMAN, KF WEINBERGER, DR TI A COMPARISON OF XE-133 AND XE-127 FOR THE DETERMINATION OF REGIONAL CEREBRAL BLOOD-FLOW MEASURED BY DYNAMIC SPECT SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY; PERFUSION; RADIOTRACER; ISOTOPES; PHANTOM STUDIES; INCREASED RESOLUTION ID EMISSION COMPUTED-TOMOGRAPHY; INERT-GAS CONCENTRATIONS; SINGLE-PHOTON; XE-133; INHALATION AB Phantom studies and cerebral blood flow (CBF) measurements in 11 normal subjects at rest were performed by single photon emission tomography (SPECT) with Xe-133 (16 mm full-width at half-maximum [FWHM] collimation) and Xe-127 (16 mm, 12 mm, and 9 mm FWHM collimation). The phantom results clearly illustrated the feasibility of Xe-127 studies and the advantage of Xe-127 over Xe-133 for equivalent patient dose exposures. CBF values obtained with Xe-127 were comparable to those of Xe-133 for the 16 mm collimator, although higher flow values were found with the better resolution, probably because of reduced partial volume effects. The correlations between the various groups of examinations were high, except for the Xe-133 and Xe-127 16 mm collimator groups. Xe-127 allows a considerable increase in the resolution of the images, while exposing the patient to a lower radiation dose. Potential limitations because of higher energy penetrating photons from Xe-127 were not observed in this specially shielded equipment. C1 NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 25 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV PY 1992 VL 45 IS 3 BP 187 EP 200 PG 14 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KG096 UT WOS:A1992KG09600005 PM 1484910 ER PT J AU RICHTERS, JE AF RICHTERS, JE TI DEPRESSED MOTHERS AS INFORMANTS ABOUT THEIR CHILDREN - A CRITICAL-REVIEW OF THE EVIDENCE FOR DISTORTION SO PSYCHOLOGICAL BULLETIN LA English DT Article ID CLINIC-REFERRED CHILDREN; PSYCHOPATHOLOGY RATING-SCALES; MATERNAL DEPRESSION; PSYCHIATRIC-DISORDERS; INTERRATER AGREEMENT; PARENTAL DEPRESSION; FATHERS PERCEPTIONS; CONDUCT DISORDER; BEHAVIOR; MALADJUSTMENT AB The claim that depressed mothers have distorted, inflated, perceptions of their children's problems has been made with increasing frequency in recent years. This review explicates the significance of the depression --> distortion controversy, introduces a set of standards for evaluating distortion claims, and uses these standards to evaluate the key characteristics of 22 studies that have published data directly relevant to the distortion question. None of the studies that claimed evidence fora depression --> distortion influence on mothers' ratings of their children met the necessary and sufficient criteria for establishing distortion. This review challenges the empirical foundation for the widely held assumption that depressed mothers have distorted perceptions of their children's problems. Issues that will require reckoning in future efforts to explore the depression --> distortion question are considered. RP RICHTERS, JE (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. OI Richters, John/0000-0002-6780-1828 NR 82 TC 429 Z9 432 U1 4 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0033-2909 J9 PSYCHOL BULL JI Psychol. Bull. PD NOV PY 1992 VL 112 IS 3 BP 485 EP 499 DI 10.1037/0033-2909.112.3.485 PG 15 WC Psychology; Psychology, Multidisciplinary SC Psychology GA JW963 UT WOS:A1992JW96300013 PM 1438639 ER PT J AU FRANCE, CP WINGER, G SEGGEL, MR RICE, KC WOODS, JH AF FRANCE, CP WINGER, G SEGGEL, MR RICE, KC WOODS, JH TI PHARMACOLOGICAL PROFILE OF A POTENT, EFFICACIOUS FENTANYL DERIVATIVE IN RHESUS-MONKEYS SO PSYCHOPHARMACOLOGY LA English DT Article DE OPIOID; DRUG DISCRIMINATION; ANALGESIA; FENTANYL; RHESUS MONKEY; COMPETITIVE ANTAGONISM; RESPIRATORY FUNCTION; SELF ADMINISTRATION ID APPARENT PA2 ANALYSIS; DIFFERENTIATION; OPIOIDS AB The recent synthesis of fentanyl derivatives, some of which appear to have novel profiles of pharmacological effects, has provided compelling evidence that mu opioid efficacy might be altered systematically by modifications in the parent compound fentanyl. In the present study a new 4-(heteroanilido)-piperidine, compound 28, was studied for its effects in rhesus monkeys. In self-administration studies compound 28 maintained rates of lever pressing similar to those maintained by alfentanil; the reinforcing effects of compound 28 were attenuated by the opioid antagonist quadazocine. In drug discrimination studies compound 28 did not substitute for the kappa agonist ethylketocyclazocine and did substitute for the mu agonist alfentanil. In morphine-treated subjects discriminating between saline and naltrexone, compound 28 did not substitute for naltrexone; however, in morphine-abstinent subjects compound 28 reversed naltrexone lever responding. Moreover, this discriminative stimulus effect in morphine-abstinent subjects was antagonized by naltrexone and by quadazocine in a manner consistent with mu receptor mediation. Compound 28 also was an effective analgesic in a warm-water, tail-withdrawal procedure and it decreased markedly respiratory function. The analgesic effects as well as the respiratory depressant effects of compound 28 were antagonized by quadazocine. Together, these results show compound 28 to be a potent, efficacious mu agonist of similar potency to alfentanil. Large differences in apparent efficacy at mu receptors between compound 28 and another compound in this series (mirfentanil), clearly demonstrate that, within this chemical family, small chemical changes can confer significant differences in pharmacologic effect. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD. UNIV MICHIGAN,DEPT PHARMACOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT PSYCHOL,ANN ARBOR,MI 48109. RP FRANCE, CP (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT PHARMACOL & EXPTL THERAPEUT,1100 FLORIDA AVE,NEW ORLEANS,LA 70119, USA. FU NIDA NIH HHS [DA 00254, DA 05018] NR 18 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1992 VL 109 IS 3 BP 291 EP 298 DI 10.1007/BF02245876 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA JY339 UT WOS:A1992JY33900006 PM 1365629 ER PT J AU BOURDON, KH RAE, DS LOCKE, BZ NARROW, WE REGIER, DA AF BOURDON, KH RAE, DS LOCKE, BZ NARROW, WE REGIER, DA TI ESTIMATING THE PREVALENCE OF MENTAL-DISORDERS IN UNITED-STATES ADULTS FROM THE EPIDEMIOLOGIC CATCHMENT-AREA SURVEY SO PUBLIC HEALTH REPORTS LA English DT Article ID DIAGNOSTIC INTERVIEW; DSM-III; HEALTH; SITES AB The National Institute of Mental Health Epidemiologic Catchment Area Survey is a comprehensive, community-based survey of mental disorders and use of services by adults, ages 18 and older. Diagnoses are based on the criteria in the "Diagnostic and Statistical Manual of Mental Disorders," third edition, and were obtained in five communities in the United States through lay-interviewer administration of the National Institute of Mental Health Diagnostic Interview Schedule. Results from the survey provide the public health field with data on the prevalence and incidence of specific mental disorders in the community, unbiased by the treatment status of the sample. The population with disorders is estimated, and the survey findings that respond to some of the most common requests for information about the epidemiology of mental disorders in the United States are highlighted briefly. Based on the survey, it is estimated that one of every five persons in the United States suffers from a mental disorder in any 6-month period, and that one of every three persons suffers a disorder in his or her lifetime. Fewer than 20 percent of those with a recent mental disorder seek help for their problem, according to the survey. High rates of comorbid substance abuse and mental disorders were found, particularly among those who had sought treatment for their disorders. C1 NIMH,DIV CLIN RES,PUBL HLTH SERV,ROCKVILLE,MD 20857. FU NIMH NIH HHS [UO1 MH 33870, UO1 MH 33883, UO1 MH 34224] NR 18 TC 94 Z9 94 U1 4 U2 5 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 NOV-DEC PY 1992 VL 107 IS 6 BP 663 EP 668 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KB799 UT WOS:A1992KB79900009 PM 1454978 ER PT J AU HARTMAN, DS HAYES, WS CHOYKE, PL TIBBETTS, GP AF HARTMAN, DS HAYES, WS CHOYKE, PL TIBBETTS, GP TI LEIOMYOSARCOMA OF THE RETROPERITONEUM AND INFERIOR VENA-CAVA - RADIOLOGIC-PATHOLOGICAL CORRELATION SO RADIOGRAPHICS LA English DT Article DE MYOMA; RETROPERITONEAL SPACE, NEOPLASMS; VENAE-CAVAE, NEOPLASMS ID BUDD-CHIARI SYNDROME; COMPUTED-TOMOGRAPHY; CLINICOPATHOLOGIC ANALYSIS; CT; SARCOMAS; DIAGNOSIS; TUMORS AB Leiomyosarcoma is the second most common primary retroperitoneal tumor in adults. Retroperitoneal leiomyosarcoma exhibits three major growth patterns: (a) completely extravascular (extraluminal) (62% of cases), (b) completely intravascular (intraluminal) (5% of cases), and (c) extra- and intraluminal (33% of cases). The usual clinical manifestation is a large abdominal mass. Intraluminal leiomyosarcoma may be accompanied by symptoms referable to venous thrombosis. The variable gross features and potential for intravascular extension result in various radiologic appearances, the most common being a large, partially necrotic soft-tissue mass in the retroperitoneum with or without extension into the inferior vena cava. Computed tomography and magnetic resonance imaging typically show a nonfatty, necrotic retroperitoneal mass and a vascular component when it is present. Ultrasound and angiography may also be useful, especially if vascular involvement is suspected from other imaging studies. Treatment of choice is complete surgical excision, which is frequently impossible due to the invasiveness of the tumor. Prognosis is related to extent of invasion and the adequacy of resection. Long-term prognosis is poor, and most patients die of local recurrence or distant metastasis. C1 ARMED FORCES INST PATHOL,DEPT RADIOL PATHOL,BLDG 54,RM M-121,ALASKA & FERN STS,WASHINGTON,DC 20306. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT RADIOL,HERSHEY,PA 17033. NIH,DEPT RADIOL,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT RADIOL & NUCL MED,BETHESDA,MD 20814. NR 33 TC 76 Z9 85 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV PY 1992 VL 12 IS 6 BP 1203 EP 1220 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JY365 UT WOS:A1992JY36500015 PM 1439022 ER PT J AU ORIJI, G GILL, JR YUN, JCH KEISER, H AF ORIJI, G GILL, JR YUN, JCH KEISER, H TI ROLE OF PROSTACYCLIN IN THE RENAL RESPONSE TO ACETYLCHOLINE SO RENAL PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article DE ACETYLCHOLINE; PROSTACYCLIN; RENAL PLASMA FLOW; SODIUM EXCRETION; INDOMETHACIN ID INDOMETHACIN-TREATED DOGS; SMOOTH-MUSCLE; ENDOTHELIAL-CELLS; RELAXING FACTOR; NITRIC-OXIDE; RELEASE; CALCIUM; RELAXATION AB Renal arterial infusion of acetylcholine (ACh; 40 mug/min) in control dogs produced a sustained rise in urinary sodium excretion (U(Na)V) and in renal plasma flow (RPF). When prostaglandin (PG) synthesis was inhibited with indomethacin (5 mg/kg), ACh produced only a transient rise in U(Na)V and RPF followed by a progressive decline in U(Na)V and RPF. Renal arterial infusion of PGI2 (0.2 mug/min) restored the response to ACh to normal in indomethacin-treated dogs. The RPF was 84+/-9 ml/min during control and increased to 132+/-19 ml/min with the infusion of PGI2 (p < 0.01). RPF increased further to 188+/-18 ml/min at 20-min infusion of ACh and was maintained at 189+/-14 ml/min at 100-min infusion of ACh (p < 0.01). Our data suggest that the initial rise in RPF by ACh is independent of the PG system, whereas maintenance of the rise in RPF by ACh requires an intact synthesis of PGs, presumably PGI2 synthesized in the vascular tissues. C1 HOWARD UNIV,COLL MED,DEPT PHYSIOL & BIOPHYS,520 W ST NW,WASHINGTON,DC 20059. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. FU NIGMS NIH HHS [SO6GM08016] NR 23 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6524 J9 RENAL PHYSIOL BIOCH JI Renal Physiol. Biochem. PD NOV-DEC PY 1992 VL 15 IS 6 BP 318 EP 324 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA KD604 UT WOS:A1992KD60400005 PM 1282725 ER PT J AU PUTNAM, FW AF PUTNAM, FW TI ALTERED STATES - PEELING AWAY THE LAYERS OF A MULTIPLE PERSONALITY SO SCIENCES-NEW YORK LA English DT Article RP PUTNAM, FW (reprint author), NIMH,DEV PSYCHOL LAB,DISSOCIAT DISORDERS UNIT,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0036-861X J9 SCIENCES JI Sci.-New York PD NOV-DEC PY 1992 VL 32 IS 6 BP 30 EP 37 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KB696 UT WOS:A1992KB69600018 ER PT J AU JAFFE, ES ZARATEOSORNO, A MEDEIROS, LJ AF JAFFE, ES ZARATEOSORNO, A MEDEIROS, LJ TI THE INTERRELATIONSHIP OF HODGKINS-DISEASE AND NON-HODGKINS-LYMPHOMAS - LESSONS LEARNED FROM COMPOSITE AND SEQUENTIAL MALIGNANCIES SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE COMPOSITE LYMPHOMA; HODGKINS DISEASE; RICHTERS SYNDROME; NON-HODGKINS LYMPHOMAS; SEQUENTIAL LYMPHOMAS RP JAFFE, ES (reprint author), NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N202,BETHESDA,MD 20892, USA. NR 0 TC 71 Z9 73 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 1992 VL 9 IS 4 BP 297 EP 303 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA JY633 UT WOS:A1992JY63300009 PM 1480852 ER PT J AU GAYDOS, CA BOBO, L WELSH, L HOOK, EW VISCIDI, R QUINN, TC AF GAYDOS, CA BOBO, L WELSH, L HOOK, EW VISCIDI, R QUINN, TC TI GENE TYPING OF CHLAMYDIA TRACHOMATIS BY POLYMERASE CHAIN-REACTION AND RESTRICTION ENDONUCLEASE DIGESTION SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID OUTER-MEMBRANE PROTEIN; NUCLEOTIDE-SEQUENCE; MONOCLONAL-ANTIBODIES; ENZYME-IMMUNOASSAY; SEROVARS AB A portion of the major outer membrane protein (MOMP) gene from 15 Chlamydia trachomatis serovars was amplified by polymerase chain reaction (PCR) and the product was analyzed by restriction fragment length polymorphism (RFLP). A set of primers was used to amplify an 871 base pair gene fragment encompassing the 4 hypervariable regions of MOMP. AluI digestion of the product gave distinctive patterns for the 15 serovars as demonstrated on silver-stained polyacrylamide gels. A triple digest with EcoRI, HinfI, and HpaII allowed improved discrimination between closely related serovars (C, H, I, J, L3). PCR and RFLP were used to type 50 wild-type clinical isolates and results were compared to results of the solid-phase enzyme immunoassay typing method. These isolates represented the most prevalent genital serovars (D, E, F, K, I and J) in the local sexually transmitted diseases clinic population. For specimens containing 1 serovar, the results of the two methods were similar for 42 samples and discordant for 1 sample. In addition, two samples showed evidence of mixed infection with two serovars as identified by both methods. Five additional specimens contained two serovars, as shown by one or both methods. In all five such specimens, the two typing methods agreed on at least one of the two serovars. For both single and multiple serovar specimens, there was concordance between the two typing methods for 16/17 E serovars, 8/9 D serovars, 8/8 F serovars, 7/7 I serovars, 7/7 J serovars, 5/8 K serovars, and 0/2 G serovars. This rapid and economic method can detect mixed infections, may circumvent the need to culture chlamydial organisms for typing, and should be a useful addition to chlamydia typing technology. C1 JOHNS HOPKINS UNIV,SCH MED,EUDOWOOD DIV PEDIAT,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP GAYDOS, CA (reprint author), JOHNS HOPKINS UNIV HOSP,DIV INFECT DIS,BLALOCK 1111,600 N WOLFE ST,BALTIMORE,MD 21205, USA. RI Gaydos, Charlotte/E-9937-2010 NR 19 TC 34 Z9 36 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD NOV-DEC PY 1992 VL 19 IS 6 BP 303 EP 308 DI 10.1097/00007435-199211000-00001 PG 6 WC Infectious Diseases SC Infectious Diseases GA JZ964 UT WOS:A1992JZ96400001 PM 1362824 ER PT J AU TAYLOR, MJ LUCIER, GW MAHLER, JF THOMPSON, M LOCKHART, AC CLARK, GC AF TAYLOR, MJ LUCIER, GW MAHLER, JF THOMPSON, M LOCKHART, AC CLARK, GC TI INHIBITION OF ACUTE TCDD TOXICITY BY TREATMENT WITH ANTITUMOR NECROSIS FACTOR ANTIBODY OR DEXAMETHASONE SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Note ID AH LOCUS; ENDOTOXIN HYPERSENSITIVITY; C57BL/6J MICE; FACTOR CACHECTIN; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; RESISTANCE; INFECTION; RECEPTOR; RAT; SUPPRESSION C1 NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,D4-04,RES TRIANGLE PK,NC 27709. SYNTEX RES,PALO ALTO,CA 94303. COMP SCI CORP,RES TRIANGLE PK,NC 27709. NR 41 TC 78 Z9 79 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1992 VL 117 IS 1 BP 126 EP 132 DI 10.1016/0041-008X(92)90227-J PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA JX895 UT WOS:A1992JX89500018 PM 1440607 ER PT J AU POSSANI, LD MARTIN, BM YATANI, A MOCHCAMORALES, J ZAMUDIO, FZ GURROLA, GB BROWN, AM AF POSSANI, LD MARTIN, BM YATANI, A MOCHCAMORALES, J ZAMUDIO, FZ GURROLA, GB BROWN, AM TI ISOLATION AND PHYSIOLOGICAL CHARACTERIZATION OF TAICATOXIN, A COMPLEX TOXIN WITH SPECIFIC EFFECTS ON CALCIUM CHANNELS SO TOXICON LA English DT Article ID OXYURANUS-S-SCUTELLATUS; PRE-SYNAPTIC NEUROTOXIN; AMINO-ACID-SEQUENCE; MEMBRANE PATCHES; SODIUM-CHANNELS; OMEGA-CONOTOXIN; K+ CHANNELS; GUINEA-PIG; VENOM; CELLS AB Taicatoxin is a new complex oligomeric toxin that was isolated from the venom of the Australian taipan snake Oxyuranus scutellatus scutellatus. It is composed of three different molecular entities: an alpha-neurotoxin-like peptide of mol. wt 8000, a neurotoxic phospholipase of mol. wt of 16,000 and a serine protease inhibitor of mol. wt 7000, linked by non-covalent bonds, at an approximate stoichiometry of 1:1:4. The most active form of the complex was isolated by ion exchange chromatography through DE-Cellulose followed by two steps of CM-Cellulose chromatography at pH 4.7 and pH 6.0, respectively. At this stage the complex migrates as a single component in beta-alanine-acetate-urea gel electrophoresis and is very toxic to mice (1 or 2 mug of the complex protein kills a mouse of 20 g within 2 hr). It blocks the high threshold calcium channel current of excitable membranes in heart and does not affect the low threshold calcium channel current. The block occurs at a site that is accessible extracellularly but not intracellularly. The block is selective for calcium channels, reversible, does not affect single channel conductance but only changes channel gating, and is voltage dependent with higher affinity for inactivated channels. The phospholipase activity of the complex toxin can be separated by affinity-chromatography using a phospholipid analog (PC-Sepharose). The resulting complex contains only alpha-neurotoxin and protease inhibitor and is still capable of blocking calcium channels, although with less potency than the native oligomeric form. Sephadex G-50 gel filtration chromatography in the presence of high salt (IM NaCl) at alkaline pH (8.2), separates the alpha-neurotoxin-like peptide from the protease inhibitor, but at this stage the resulting peptides lose physiological activity towards the calcium channels. The amino acid sequence of the protease inhibitor was determined by automatic Edman degradation. The alpha-neurotoxin-like peptide and two isosubunits displaying phospholipase activity were sequenced at the N-terminal part of the molecule. C1 BAYLOR COLL MED, DEPT PHYSIOL & MOLEC BIOPHYS, HOUSTON, TX 77030 USA. NIMH, CLIN NEUROSCI BRANCH, MOLEC NEUROGENET UNIT, BETHESDA, MD 20892 USA. RP UNIV NACL AUTONOMA MEXICO, INST BIOTECNOL, DEPT BIOQUIM, APARTADO POSTAL 510-3, CUERNAVACA 62271, MEXICO. RI Possani, Lourival/J-2397-2013 FU NHLBI NIH HHS [HL37044] NR 46 TC 47 Z9 50 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD NOV PY 1992 VL 30 IS 11 BP 1343 EP 1364 DI 10.1016/0041-0101(92)90511-3 PG 22 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA JY669 UT WOS:A1992JY66900003 PM 1485334 ER PT J AU KLEINMAN, S ALTER, H BUSCH, M HOLLAND, P TEGTMEIER, G NELLES, M LEE, S PAGE, E WILBER, J POLITO, A AF KLEINMAN, S ALTER, H BUSCH, M HOLLAND, P TEGTMEIER, G NELLES, M LEE, S PAGE, E WILBER, J POLITO, A TI INCREASED DETECTION OF HEPATITIS C VIRUS (HCV)-INFECTED BLOOD-DONORS BY A MULTIPLE-ANTIGEN HCV ENZYME-IMMUNOASSAY SO TRANSFUSION LA English DT Article ID NON-B-HEPATITIS; RECOMBINANT IMMUNOBLOT ASSAY; NON-A; TRANSFUSION; ANTIBODIES; INFECTION AB A new, multiple-antigen enzyme immunoassay (EIA-2) for hepatitis C virus (HCV) antibodies was evaluated in parallel with the previously available c100-3 HCV EIA (EIA-1) in 14,068 volunteer blood donors as well as in 25 cases of transfusion-associated hepatitis C for which recipient and donor samples were available. When compared to EIA-1, the EIA-2 was more sensitive in detecting HCV-infected blood donors. The EIA-2 detected an additional 1 in 1000 EIA-1-negative, surrogate marker-negative donors who were infected with HCV as demonstrated by polymerase chain reaction (PCR). The specificity of the EIA-2 was comparable to that of the EIA-1, but the two tests appear to detect different populations of false-positive donors. Recombinant immunoblot assay-indeterminate donors were detected five times more frequently by the EIA-2; PCR demonstrated that 21 percent of these donors were infected with HCV. The greater sensitivity of EIA-2 was also found in 25 transfusion recipients with non-A,non-B hepatitis; however, in 16 percent of these cases of posttransfusion HCV infection, the EIA-2 failed to detect an HCV-seropositive donor. These data indicate that EIA-2 testing will significantly reduce. but probably not eliminate, the risk of transfusion-associated HCV infection; we estimate this residual per-unit risk to be 1 in 2000 to 1 in 6000 units transfused. On a national level, it is projected that the replacement of the anti-HCV EIA-1 with the EIA-2 will initially prevent up to 40 additional cases of transfusion-associated hepatitis C per day. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,IMMUNOL SECT,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94110. IRWIN MEM BLOOD CTR,SAN FRANCISCO,CA. SACRAMENTO MED FDN CTR BLOOD RES,SACRAMENTO,CA. COMMUNITY BLOOD CTR GREATER KANSAS CITY,KANSAS CITY,MO. ORTHO DIAGNOST INC,RARITAN,NJ. CHIRON CORP,EMERYVILLE,CA. AMER RED CROSS BLOOD SERV,LOS ANGELES,CA. RP KLEINMAN, S (reprint author), UNIV CALIF LOS ANGELES,MED CTR BLOOD BANK,A4-239,10833 LE CONTE AVE,LOS ANGELES,CA 90024, USA. NR 17 TC 136 Z9 138 U1 0 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV-DEC PY 1992 VL 32 IS 9 BP 805 EP 813 DI 10.1046/j.1537-2995.1992.32993110750.x PG 9 WC Hematology SC Hematology GA KC094 UT WOS:A1992KC09400004 PM 1471243 ER PT J AU LENFANT, C AF LENFANT, C TI TRANSFUSION PRACTICE SHOULD BE AUDITED FOR BOTH UNDERTRANSFUSION AND OVERTRANSFUSION SO TRANSFUSION LA English DT Letter RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 5 TC 32 Z9 32 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 NOV-DEC PY 1992 VL 32 IS 9 BP 873 EP 874 DI 10.1046/j.1537-2995.1992.32993110764.x PG 2 WC Hematology SC Hematology GA KC094 UT WOS:A1992KC09400020 PM 1471253 ER PT J AU SUNDT, TM ARN, JS SACHS, DH AF SUNDT, TM ARN, JS SACHS, DH TI PATTERNS OF T-CELL ACCESSORY CELL-INTERACTION IN THE GENERATION OF PRIMARY ALLORESPONSES IN THE PIG SO TRANSPLANTATION LA English DT Article ID MONOCLONAL-ANTIBODIES; MINIATURE SWINE; CYCLOSPORINE-A; PATHWAYS; ALLOANTIGENS; ACTIVATION; REJECTION AB Partially inbred, MHC-homozygous miniature swine provide a unique model for the study of organ transplantation and the induction of tolerance in large animals. Models of both vascularized solid organ transplantation and bone marrow transplantation have previously been established. The availability of monoclonal antibodies reactive with porcine leukocyte subset antigens now makes possible studies of the cellular immunology in this species, affording the opportunity to examine mechanisms of transplant tolerance and graft rejection in increasing detail. Using such antibodies and peripheral blood leukocytes from pigs of recombinant MHC haplotypes, we have examined porcine T cell-accessory cell interactions in vitro with attention to T cell subsets and the class of MHC alloantigen stimulation. Primary allospecific MLR and CML cultures were studied after depletion of accessory cells from responder and/or stimulator populations. Although class II MHC antigens were expressed on the majority of porcine T cells before and after depletion, these cells were insufficient for antigen presentation, since there was an absolute requirement for ACs in the generation of primary alloresponses. Proliferative and CTL alloresponses could be generated provided that ACs of either stimulator or responder type were present. Selective depletion of CD4+ T cells from the responder population demonstrated: (a) that the interaction mediated by self ACs was CD4-dependent; (b) that two pathways exist for interaction involving allogeneic ACs; and (c) that the interaction involving allogeneic class II is CD4-dependent, while that with allogeneic class I is not. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,TRANSPLANTAT BIOL SECT,ROCKVILLE,MD 20892. FU NCI NIH HHS [1 R01 CA55553-01]; NIAID NIH HHS [1 R01 AI31046-01] NR 18 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV PY 1992 VL 54 IS 5 BP 911 EP 916 DI 10.1097/00007890-199211000-00027 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA JY228 UT WOS:A1992JY22800027 PM 1440858 ER PT J AU KASLOW, DC BATHURST, IC BARR, PJ AF KASLOW, DC BATHURST, IC BARR, PJ TI MALARIA TRANSMISSION-BLOCKING VACCINES SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID PAPUA-NEW-GUINEA; PLASMODIUM-FALCIPARUM; SEXUAL STAGE; HUMAN-POPULATIONS; ANTIGENS; ANTIBODIES; CANDIDATE; IMMUNITY; PROTEIN; TARGET AB Antibodies to surface proteins of the sexual stages of Plasmodium falciparum block completely the transmission of these malaria parasites, Transmission-blocking vaccines therefore represent a powerful and novel approach to controlling the spread of this lethal disease. C1 CHIRON CORP,EMERYVILLE,CA. LXR BIOTECHNOL INC,RICHMOND,CA 94806. RP KASLOW, DC (reprint author), NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,BETHESDA,MD 20892, USA. NR 27 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD NOV PY 1992 VL 10 IS 11 BP 388 EP 391 DI 10.1016/0167-7799(92)90280-9 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA JZ381 UT WOS:A1992JZ38100008 PM 1368880 ER PT J AU SEGEV, I AF SEGEV, I TI SINGLE NEURON MODELS - OVERSIMPLE, COMPLEX AND REDUCED SO TRENDS IN NEUROSCIENCES LA English DT Review ID DENDRITIC SPINES; ALPHA-MOTONEURONS; CALCIUM; POTENTIALS; DYNAMICS; INSIGHTS; CELLS AB The single neurone stands in the midst of a controversy among modelers. Some believe that its details are functionally superfluous when the neurone operates in a large network, and very simple models can be used to represent the input/output characteristics of neurones. Others claim that the unique morphology and electrical properties of neurones do play an important role. Complicated models of neurones are developed to reveal how the various kinds of 'neurone-ware' (dendrites, spines, axons, membrane channels and synapses) create a computationally powerful unit. Various models are discussed, including new carefully reduced models that retain essential features of more complex models. Such intermediate models will play a central role in our efforts to understand information processing in large neuronal networks. C1 NIDDK,MATH RES BRANCH,BETHESDA,MD 20892. RP SEGEV, I (reprint author), HEBREW UNIV JERUSALEM,INST LIFE SCI,DEPT NEUROBIOL,IL-91904 JERUSALEM,ISRAEL. NR 66 TC 83 Z9 85 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 1992 VL 15 IS 11 BP 414 EP 421 DI 10.1016/0166-2236(92)90003-Q PG 8 WC Neurosciences SC Neurosciences & Neurology GA JU747 UT WOS:A1992JU74700002 PM 1281347 ER PT J AU COHEN, AH ERMENTROUT, GB KIEMEL, T KOPELL, N SIGVARDT, KA WILLIAMS, TL AF COHEN, AH ERMENTROUT, GB KIEMEL, T KOPELL, N SIGVARDT, KA WILLIAMS, TL TI MODELING OF INTERSEGMENTAL COORDINATION IN THE LAMPREY CENTRAL PATTERN GENERATOR FOR LOCOMOTION SO TRENDS IN NEUROSCIENCES LA English DT Review ID COUPLED NEURAL OSCILLATORS; SPINAL-CORD; CHAINS; INTERNEURONS; SYSTEMS AB Rhythmic motor activity requires coordination of different muscles or muscle groups so that they are all active with the same cycle duration and appropriate phase relationships. The neural mechanisms for such phase coupling in vertebrate locomotion are not known. Swimming in the lamprey is accomplished by the generation of a travelling wave of body curvature in which the phase coupling between segments is so controlled as to give approximately one full wavelength on the body at any swimming speed This article reviews work that has combined mathematical analysis, biological experimentation and computer simulation to provide a conceptual framework within which intersegmental coordination can be investigated. Evidence is provided to suggest that in the lamprey, ascending coupling is dominant over descending coupling and controls the intersegmental phase lag during locomotion. The significance of long-range intersegmental coupling is also discussed. C1 UNIV PITTSBURGH,DEPT MATH,PITTSBURGH,PA 15260. NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. UNIV CALIF DAVIS,VET ADM MED CTR,DEPT NEUROL,MARTINEZ,CA 94553. UNIV LONDON ST GEORGES HOSP,SCH MED,DEPT PHYSIOL,LONDON SW17 0RE,ENGLAND. RP COHEN, AH (reprint author), UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20770, USA. NR 29 TC 134 Z9 137 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 1992 VL 15 IS 11 BP 434 EP 438 DI 10.1016/0166-2236(92)90006-T PG 5 WC Neurosciences SC Neurosciences & Neurology GA JU747 UT WOS:A1992JU74700005 PM 1281350 ER PT J AU LIU, BCS LIOTTA, LA AF LIU, BCS LIOTTA, LA TI BIOCHEMISTRY OF BLADDER-CANCER INVASION AND METASTASIS - CLINICAL IMPLICATIONS SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PLASMINOGEN ACTIVATORS; MELANOMA-CELLS; NUCLEAR MATRIX; BREAST-CANCER; CATHEPSIN-B; TUMOR-CELLS; MEMBRANE; LAMININ; KINASE; MOTILITY C1 CUNY MT SINAI SCH MED,DEPT UROL,NEW YORK,NY 10029. NCI,PATHOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [1R01CA-51968] NR 38 TC 19 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD NOV PY 1992 VL 19 IS 4 BP 621 EP 627 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA LA257 UT WOS:A1992LA25700002 PM 1441020 ER PT J AU GUPTA, S KAGEYAMA, S AF GUPTA, S KAGEYAMA, S TI VARIANCE-BALANCED DESIGNS WITH UNEQUAL BLOCK SIZES AND UNEQUAL REPLICATIONS SO UTILITAS MATHEMATICA LA English DT Article ID GROUP DIVISIBLE DESIGNS; PAIRWISE AB An approach is developed for obtaining variance balanced designs. The approach is based upon the idea of augmentation and is not restricted to equi-block sized and/or equi-replicate variance balanced designs. A table of such designs in which treatment replications arc at most 30 is also given. Plans of the tabulated designs can be readily obtained using available sources. C1 NO ILLINOIS UNIV,DE KALB,IL 60115. NIH,BETHESDA,MD 20892. HIROSHIMA UNIV,HIROSHIMA 730,JAPAN. NR 30 TC 9 Z9 9 U1 0 U2 0 PU UTIL MATH PUBL INC PI WINNIPEG PA UNIV MANITOBA PO BOX 7 UNIV CENT, WINNIPEG MB R3T 2N2, CANADA SN 0315-3681 J9 UTILITAS MATHEMATICA JI Util. Math. PD NOV PY 1992 VL 42 BP 15 EP 24 PG 10 WC Mathematics, Applied; Statistics & Probability SC Mathematics GA KJ401 UT WOS:A1992KJ40100002 ER PT J AU CREMER, KJ GRUBER, J AF CREMER, KJ GRUBER, J TI ANIMAL-MODELS OF RETROVIRUS-ASSOCIATED MALIGNANCIES SO VETERINARY PATHOLOGY LA English DT Editorial Material ID FELINE LEUKEMIA-VIRUS; SHEEP PULMONARY ADENOMATOSIS; ENZOOTIC BOVINE LEUKOSIS; IMMUNODEFICIENCY VIRUS; PERSISTENT LYMPHOCYTOSIS; SIMIAN AIDS; DISEASE; CATS; CARCINOMA; CATTLE RP CREMER, KJ (reprint author), NCI,BIOL CARCINOGENESIS BRANCH,EXECUT PLAZA N,ROOM 540,BETHESDA,MD 20892, USA. NR 50 TC 9 Z9 9 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD NOV PY 1992 VL 29 IS 6 BP 572 EP 578 PG 7 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA JY748 UT WOS:A1992JY74800022 PM 1360178 ER PT J AU ZOLLER, B OZATO, K KROEMER, G AUFFRAY, C JUNGWIRTH, C AF ZOLLER, B OZATO, K KROEMER, G AUFFRAY, C JUNGWIRTH, C TI INTERFERON INDUCTION OF CHICKEN MHC CLASS-I GENE-EXPRESSION - PHYLOGENETIC CONSERVATION OF THE INTERFERON-RESPONSIVE ELEMENT SO VIROLOGY LA English DT Article ID INDUCIBLE ENHANCER ELEMENT; REGULATORY ELEMENTS; INDUCED TRANSCRIPTION; STIMULATED TRANSCRIPTION; CONSENSUS SEQUENCE; SYNTHETASE GENE; MAMMALIAN-CELLS; NUCLEAR FACTORS; B-GENE; PROTEIN C1 UNIV WURZBURG,INST VIROL & IMMUNOBIOL,W-8700 WURZBURG,GERMANY. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. CSIC,CTR BIOL MOLEC,E-28049 MADRID,SPAIN. RI Kroemer, Guido/B-4263-2013 NR 46 TC 17 Z9 17 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 NOV PY 1992 VL 191 IS 1 BP 141 EP 149 DI 10.1016/0042-6822(92)90175-O PG 9 WC Virology SC Virology GA JT446 UT WOS:A1992JT44600016 PM 1384229 ER PT J AU HARDY, ME GORZIGLIA, M WOODE, GN AF HARDY, ME GORZIGLIA, M WOODE, GN TI AMINO-ACID-SEQUENCE ANALYSIS OF BOVINE ROTAVIRUS B223 REVEALS A UNIQUE OUTER CAPSID PROTEIN-VP4 AND CONFIRMS A 3RD-BOVINE VP4-TYPE SO VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; PORCINE ROTAVIRUS; RHESUS ROTAVIRUS; NEUTRALIZATION EPITOPES; MONOCLONAL-ANTIBODIES; GENOMIC CHARACTERIZATION; CRYOELECTRON MICROSCOPY; ANTIGENIC RELATIONSHIPS; 3-DIMENSIONAL STRUCTURE; GNOTOBIOTIC CALVES C1 TEXAS A&M UNIV SYST,COLL VET MED,DEPT VET PATHOBIOL,COLL STN,TX 77843. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 61 TC 50 Z9 51 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 NOV PY 1992 VL 191 IS 1 BP 291 EP 300 DI 10.1016/0042-6822(92)90191-Q PG 10 WC Virology SC Virology GA JT446 UT WOS:A1992JT44600032 PM 1329320 ER PT J AU CARTER, BJ ANTONI, BA KLESSIG, DF AF CARTER, BJ ANTONI, BA KLESSIG, DF TI ADENOVIRUS CONTAINING A DELETION OF THE EARLY REGION 2A-GENE ALLOWS GROWTH OF ADENOASSOCIATED VIRUS WITH DECREASED EFFICIENCY SO VIROLOGY LA English DT Note ID DNA-BINDING PROTEIN; HELPER ACTIVITY; REP PROTEIN; REPLICATION; GENE; TYPE-5; CELLS; EXPRESSION; MUTANTS; GENOME C1 RUTGERS STATE UNIV,WAKSMAN INST,PISCATAWAY,NJ 08855. RP CARTER, BJ (reprint author), NIDDKD,MOLEC & CELLULAR BIOL LAB,BLDG 8,ROOM 304,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI23591] NR 32 TC 26 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1992 VL 191 IS 1 BP 473 EP 476 DI 10.1016/0042-6822(92)90213-9 PG 4 WC Virology SC Virology GA JT446 UT WOS:A1992JT44600054 PM 1329332 ER PT J AU LAWSON, CM SUBBARAO, EK MURPHY, BR AF LAWSON, CM SUBBARAO, EK MURPHY, BR TI NUCLEOTIDE-SEQUENCE CHANGES IN THE POLYMERASE BASIC PROTEIN-2 GENE OF TEMPERATURE-SENSITIVE MUTANTS OF INFLUENZA-A VIRUS SO VIROLOGY LA English DT Note ID INFLUENZA-A/UDORN/72 H3N2 VIRUS; COMPLEMENTATION RP LAWSON, CM (reprint author), NIAID,INFECT DIS LAB,BLDG 7,ROOM 106,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 22 Z9 24 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1992 VL 191 IS 1 BP 506 EP 510 DI 10.1016/0042-6822(92)90221-A PG 5 WC Virology SC Virology GA JT446 UT WOS:A1992JT44600062 PM 1413525 ER PT J AU TASAKI, I BYRNE, PM AF TASAKI, I BYRNE, PM TI RAPID STRUCTURAL-CHANGES IN NERVE-FIBERS EVOKED BY ELECTRIC-CURRENT PULSES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACTION-POTENTIALS RP TASAKI, I (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 13 TC 59 Z9 59 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 30 PY 1992 VL 188 IS 2 BP 559 EP 564 DI 10.1016/0006-291X(92)91092-5 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JV618 UT WOS:A1992JV61800012 PM 1445300 ER PT J AU SCHALK, EM GOSIEWSKA, A PRATHER, W PETERKOFSKY, B AF SCHALK, EM GOSIEWSKA, A PRATHER, W PETERKOFSKY, B TI POSTTRANSCRIPTIONAL REGULATION OF THE PRO-ALPHA-1(I) COLLAGEN GENE IN PRO-ALPHA-1(I)-DEFICIENT, CHEMICALLY TRANSFORMED SYRIAN-HAMSTER EMBRYO FIBROBLASTS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MESSENGER-RNA; EXPRESSION; CELLS C1 NCI,BIOCHEM LAB,BLDG 37,ROOM 4C-18,BETHESDA,MD 20892. NR 23 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 30 PY 1992 VL 188 IS 2 BP 780 EP 785 DI 10.1016/0006-291X(92)91124-9 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JV618 UT WOS:A1992JV61800044 PM 1280122 ER PT J AU TOPOL, LZ TATOSYAN, AG ASCIONE, R THOMPSON, DM BLAIR, DG KOLA, I SETH, A AF TOPOL, LZ TATOSYAN, AG ASCIONE, R THOMPSON, DM BLAIR, DG KOLA, I SETH, A TI C-ETS-1 PROTOONCOGENE EXPRESSION ALTERS THE GROWTH-PROPERTIES OF IMMORTALIZED RAT FIBROBLASTS SO CANCER LETTERS LA English DT Article DE C-ETS-1 PROTOONCOGENE; RAT EMBRYO FIBROBLASTS; IMMORTALIZATION; TRANSFORMATION ID ONCOGENIC ACTIVITY; TRANSFORMATION; SEQUENCES; CELLS; DNA; RNA AB Ets family genes have been cloned and characterized from a variety of species ranging from human to Drosophila. The ets proteins encode transcription factors that activate transcription via specific binding to GGAA core sequence present in various promoter/enhancers. To investigate the role of ets protooncogene expression on the growth properties of rat embryo fibroblasts (REF), we constructed and introduced ets expression vectors into primary, as well as immortalized REF cells. The transfected cells contained multiple copies of the vector DNA, and the Northern blot analysis demonstrated overexpression of the c-ets-1-specific mRNA. Although the expression of the ets genes was unable to immortalize primary rat embryo fibroblasts, the expression of ets-1 in REF-1 cells enabled their growth in serum-free medium and effected tumorigenic activity in nude mice. C1 CANC RES CTR,MOSCOW,USSR. CTR EARLY HUMAN DEV,CLAYTON,VIC,AUSTRALIA. RP TOPOL, LZ (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. RI Kola, Ismail/C-5254-2013 NR 23 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 30 PY 1992 VL 67 IS 1 BP 71 EP 78 DI 10.1016/0304-3835(92)90010-S PG 8 WC Oncology SC Oncology GA JZ550 UT WOS:A1992JZ55000009 PM 1423247 ER PT J AU KINGSLEY, DM BLAND, AE GRUBBER, JM MARKER, PC RUSSELL, LB COPELAND, NG JENKINS, NA AF KINGSLEY, DM BLAND, AE GRUBBER, JM MARKER, PC RUSSELL, LB COPELAND, NG JENKINS, NA TI THE MOUSE SHORT-EAR SKELETAL MORPHOGENESIS LOCUS IS ASSOCIATED WITH DEFECTS IN A BONE MORPHOGENETIC MEMBER OF THE TGF-BETA SUPERFAMILY SO CELL LA English DT Article ID TRANSFORMING GROWTH-FACTOR; MESODERM-INDUCING FACTOR; GENETIC-LINKAGE MAP; MESSENGER-RNA; EMBRYONIC-DEVELOPMENT; OSTEOGENIC PROTEIN; PATTERN-FORMATION; RETINOIC ACID; GERM LAYERS; ACTIVIN-A AB The mouse short ear gene is required for normal growth and patterning of skeletal structures, and for repair of bone fractures in adults. We have carried out an extensive chromosome walk in the chromosome region that surrounds this locus. Here we show that the short ear region contains the gene for a TGFbeta-related protein called bone morphogenetic protein 5 (Bmp-5). This gene is deleted or rearranged in several independent mutations at the short ear locus. Mice homozygous for large deletions of the Bmp-5 coding region are viable and fertile. Mutations at the short ear locus provide an important new tool for defining the normal functions of BMPs in mammals. The specific skeletal defects seen in short-eared animals, which occur against a background of otherwise normal skeletal structures, suggest that particular aspects of skeletal morphology may be determined by individual members of a family of signaling factors that can induce the formation of cartilage and bone in vivo. C1 OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP KINGSLEY, DM (reprint author), STANFORD UNIV,MED CTR,SCH MED,DEPT DEV BIOL,BECKMAN CTR B300,STANFORD,CA 94305, USA. FU NCI NIH HHS [N01-CO-74101] NR 66 TC 387 Z9 395 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 30 PY 1992 VL 71 IS 3 BP 399 EP 410 DI 10.1016/0092-8674(92)90510-J PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JW435 UT WOS:A1992JW43500007 PM 1339316 ER PT J AU ALLEN, MS LALOGGIA, AJ DORN, LJ MARTIN, MJ COSTANTINO, G HAGEN, TJ KOEHLER, KF SKOLNICK, P COOK, JM AF ALLEN, MS LALOGGIA, AJ DORN, LJ MARTIN, MJ COSTANTINO, G HAGEN, TJ KOEHLER, KF SKOLNICK, P COOK, JM TI PREDICTIVE BINDING OF BETA-CARBOLINE INVERSE AGONISTS AND ANTAGONISTS VIA THE COMFA GOLPE APPROACH SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BENZODIAZEPINE RECEPTORS; MEMORY IMPAIRMENT; PHARMACOPHORE; PERFORMANCE AB The synthesis and affinities of six new 3-substituted beta-carbolines (6-10,12) for the benzodiazepine receptor (BzR) are described. These analogs were used both to probe the dimensions of the hydrophobic pocket in the benzodiazepine receptor and to test the predictive ability of a previously reported 3D-QSAR regression model. Of the new analogs synthesized, the gamma-branched derivatives (isobutoxy, 7, IC50 = 93 nM; isopentoxy, 9, IC50 = 104 nM) display significantly higher affinity for the BzR than either the beta-branched (sec-butoxy, 6, IC50 = 471 nM; tert-butyl ketone, 12, IC50 = 358 nM) or delta-branched (isopentoxy, 8, IC50 = 535 nM) analogs. An exception to this rule is the gamma-branched 3-benzyloxy derivative 10 (IC50 > 1000 nM) which appears to have a chain length that is too long to be accommodated by the BzR. The standard error of prediction for these six new beta-carbolines using the original regression model is significantly lower than the standard error estimate of the cross validation runs on the training set, hence the predictions made using this model are much better than expected. In order to obtain more credible predictions, a new procedure called GOLPE (generating optimal linear PLS estimates) was used to eliminate irrelevant electrostatic and steric descriptors from the regression equation. A substantial reduction in the standard error estimate resulted. The predictions from this new regression equation were somewhat less accurate than the ones obtained with the original regression equation; however the standard error of prediction and the standard error estimate are in much closer agreement. Finally, to probe the effect that the quality of the steric and electrostatic potentials has on 3D-QSAR analyses, the semiempirical MNDO//PRDDOE geometries and Mulliken charges used in the original analyses were replaced with ab initio 3-21G//6-31G* geometries and electrostatic potential fit charges. A modest decrease in the standard error estimate and increase in cross validated R2 resulted. C1 SEARLE RES & DEV, DRUG DESIGN SECT, SKOKIE, IL 60077 USA. UNIV WISCONSIN, DEPT CHEM, MILWAUKEE, WI 53201 USA. UNIV PERUGIA, DIPARTIMENTO CHEM, CHEMIOMETRIA LAB, I-06100 PERUGIA, ITALY. NIDDKD, NEUROSCI LAB, BETHESDA, MD 20892 USA. RI Hagen, Timothy/A-8971-2013 NR 31 TC 54 Z9 55 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 30 PY 1992 VL 35 IS 22 BP 4001 EP 4010 DI 10.1021/jm00100a004 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JW906 UT WOS:A1992JW90600004 PM 1331452 ER PT J AU MEGATI, S GOREN, Z SILVERTON, JV ORLINA, J NISHIMURA, H SHIRASAKI, T MITSUYA, H ZEMLICKA, J AF MEGATI, S GOREN, Z SILVERTON, JV ORLINA, J NISHIMURA, H SHIRASAKI, T MITSUYA, H ZEMLICKA, J TI (R)-(-)-ADENALLENE AND (S)-(+)-ADENALLENE - SYNTHESIS, ABSOLUTE-CONFIGURATION, ENANTIOSELECTIVITY OF ANTIRETROVIRAL EFFECT, AND ENZYMATIC DEAMINATION SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACYCLIC NUCLEOSIDE ANALOGS; ANTITUMOR-ACTIVITY; CONFORMATION; AGENTS; ACID; DDC AB Synthesis of optically pure (-)- and (+)-adenallene 2 and 3 is described. Racemic adenallene (1a) was subjected to deamination with adenosine deaminase monitored by HPLC using a Chiralcel CA-l column to give (-)-adenallene (2) and (+)-hypoxallene (4). The latter compound was converted to acetate 5. The reaction of 5 with trifluoromethanesulfonic anhydride and pyridine followed by ammonolysis furnished acetate 6 or (+)-adenallene (3) depending on the solvent used in the last step. Acetate 5 was smoothly transformed to the 6-chloro derivative 7, but an attempted ammonolysis led only to racemization and decomposition. Single crystal X-ray diffraction established the R-configuration of (-)-enantiomer 2. The latter forms a pseudosymmetric dimer in the lattice with the adenine moiety in an anti-like conformation. The torsional angles of the allenic bonds show departures from 90-degrees (91 and 97-degrees, respectively) and rotameric preference of the hydroxymethyl groups is different in both molecules of the dimer. The R-enantiomer 2 inhibited the replication and cytopathic effect of human immunodeficiency virus (HIV-1) in ATH8 cell culture with an IC50 of 5.8 muM, whereas the S-enantiomer 3 was less active (IC50 > 200 muM). The enantioselectivity of the anti-HIV effect is significantly lower than that of 2',3'-dideoxyadenosine. Kinetics of deamination of R- and S-enantiomers 2 and 3 catalyzed by adenosine deaminase gave the following parameters: K(m) values of R-form 3 and S-form 2 were 0.41 and 0.52 mM with V(max) being 530 and 18.5 mumol/min, respectively. Again, a much lower level of enantioselectivity of deamination was observed than that Of D- and L-adenosine. These results indicate (i) different enantioselectivity of enantiomers 2 and 3 as HIV inhibitors and adenosine deaminase substrates and (ii) both R- and S-enantiomers 2 and 3 can function as nucleoside analogues with varied enantioselectivity for different enzymes or receptors. C1 MICHIGAN CANC FDN,DEPT CHEM,DETROIT,MI 48201. NHLBI,BETHESDA,MD 20892. CHIRAL TECHNOL INC,EXTON,PA 19341. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. WAYNE STATE UNIV,SCH MED,DEPT INTERNAL MED,DETROIT,MI 48201. WAYNE STATE UNIV,SCH MED,DEPT BIOCHEM,DETROIT,MI 48201. FU NCI NIH HHS [CA32779] NR 49 TC 34 Z9 34 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 30 PY 1992 VL 35 IS 22 BP 4098 EP 4104 DI 10.1021/jm00100a016 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JW906 UT WOS:A1992JW90600016 PM 1304169 ER PT J AU MARTIN, MJ TRUDELL, ML ARAUZO, HD ALLEN, MS LALOGGIA, AJ LI, D SCHULTZ, CA TAN, YC BI, YZ NARAYANAN, K DORN, LJ KOEHLER, KF SKOLNICK, P COOK, JM AF MARTIN, MJ TRUDELL, ML ARAUZO, HD ALLEN, MS LALOGGIA, AJ LI, D SCHULTZ, CA TAN, YC BI, YZ NARAYANAN, K DORN, LJ KOEHLER, KF SKOLNICK, P COOK, JM TI MOLECULAR YARDSTICKS - RIGID PROBES TO DEFINE THE SPATIAL DIMENSIONS OF THE BENZODIAZEPINE RECEPTOR-BINDING SITE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID INVERSE AGONIST; BETA-CARBOLINES; GABAA RECEPTOR; INDOLE AREA; LIGANDS; PHARMACOPHORE; OXIDATIONS; COMPLEX; SUBUNIT; CELLS AB A series of rigid planar azadiindoles (8a, 8b, and 8d), benzannelated pyridodiindoles (11a, 11b, and 11d), and indolopyridoimidazoles (11c, 20, and 24) were synthesized from 4-oxo-1,2,3,4-tetrahydro-beta-carboline 5 via the Fischer indole cyclization with the appropriate arylhydrazines. These analogues were employed as probes ("molecular yardsticks") to define the spatial dimensions of the lipophilic regions of the benzodiazepine receptor (BzR) binding cleft. Benzannelated indoles 11a-d and indolopyridoimidazoles 20 and 24 were important in establishing an area of negative interaction (S1, see Figure 6, part b) in the binding cleft common to the interactions of both inverse agonists and agonists. Data from this chemical and computer-assisted analysis of the pharmacophore (see Figure 6) indicates that inverse agonists and agonists bind to the same binding region, but the pharmacophoric descriptors required for the two activities are different, in keeping with previous studies with these planar ligands. However, the hydrogen bond donating site H-1 and the lipophilic region L1 in the receptor binding site are common interactions experienced by both series of ligands. The low affinities of both indolo[3,2-c]carbazole (3a) and indolo[3,2-b]isoquinoline (3b) for the BzR are consonant with the requirements of a hydrogen bond acceptor interaction at donor site H-1 and a hydrogen bond donor interaction at acceptor site A2 for potent inverse agonist activity in the beta-carboline series. The hydrochloride salts of 1-aza- 8a (IC50 10.6 nM), 2-aza- 8b (IC50 51.5 nM), and 4-azadiindole 8d (IC50 11.2 nM) were found to be much more soluble in water than the corresponding salt of the parent diindole 2. Moreover, aza analogues 8a and 8b were shown to be partial inverse agonists with proconvulsant potencies comparable to that of the parent diindole 2. C1 UNIV WISCONSIN,DEPT CHEM,MILWAUKEE,WI 53201. SEARLE RES & DEV,DRUG DESIGN SECT,SKOKIE,IL 60077. NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. FU NIMH NIH HHS [MH 36644]; NINDS NIH HHS [NS 22287] NR 69 TC 54 Z9 54 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 30 PY 1992 VL 35 IS 22 BP 4105 EP 4117 DI 10.1021/jm00100a017 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JW906 UT WOS:A1992JW90600017 PM 1331457 ER PT J AU NEWMAN, AH BEVAN, K BOWERY, N TORTELLA, FC AF NEWMAN, AH BEVAN, K BOWERY, N TORTELLA, FC TI SYNTHESIS AND EVALUATION OF 3-SUBSTITUTED 17-METHYLMORPHINAN ANALOGS AS POTENTIAL ANTICONVULSANT AGENTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GUINEA-PIG BRAIN; DEXTROMETHORPHAN BINDING-SITES; METHYL-D-ASPARTATE; PHENCYCLIDINE-LIKE DRUGS; RECEPTOR COMPLEX; H-3 GLYCINE; RAT-BRAIN; DEXTRORPHAN; METABOLISM; ACID AB Dextromethorphan (1, (+)-3-methoxy-17-methylmorphinan) demonstrates anticonvulsant activity in a variety of in vitro and in vivo models of convulsive action. It is well known that 1 is metabolized to its phenolic derivative dextrorphan (2) and this metabolite is also a potent anticonvulsant. A series of (+)-3-substituted-17-methylmorphinans, which are structurally similar to 1 but are either not expected to be metabolized to 2 or might do so at a reduced rate, as compared to 1, were prepared. Three analogs, 5 ((+)-3-amino-17-methylmorphinan), 14 ((+)-3-ethoxy-17-methylmorphinan), and 15 ((+)-3-(2-propoxy)-17-methylmorphinan) were found to possess potent anticonvulsant activity with full efficacy (ED50 25, 5.6, and 3.9 mg/kg, sc, respectively) in the rat supramaximal electroshock (MES) test. Binding potencies of these compounds to receptor sites labeled with [H-3]dextromethorphan ([H-1]1), in rat brain and guinea pig brain subcellular fractions, and [H-3]thienylcyclohexylpiperidine (TCP) and [H-3]glycine in rat brain, were determined. Most of the analogs displaced [H-3]1 from its binding sites, with compounds 14 (IC50 0.42 muM) and 15 (IC50 0.88 muM) having equivalent potencies to 1 (IC50 0.59 muM), in rat brain, and no appreciable activity at the [H-3]TCP or [3H]glycine-labeled sites. Compound 5 did not bind with appreciable activity to the [H-3]1 site, in rat brain, but did bind to the [H-3]TCP site with lower potency than the parent 1 (IC50 7.8 and 2.0 muM, respectively). The mechanism of anticonvulsant action of these agents is not clear although it appears that interaction at the [H-3]1 sites may be involved. C1 WALTER REED ARMY INST RES,DEPT APPL BIOCHEM,WASHINGTON,DC 20307. UNIV LONDON,SCH PHARM,DEPT PHARMACOL,LONDON WC1N 1AX,ENGLAND. WALTER REED ARMY INST RES,NEUROPHARMACOL BRANCH,WASHINGTON,DC 20307. RP NEWMAN, AH (reprint author), NIDA,ADDICT RES CTR,PSYCHOBIOL LAB,DRUG DEV GRP,POB 5180,BALTIMORE,MD 21224, USA. NR 52 TC 21 Z9 21 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 30 PY 1992 VL 35 IS 22 BP 4135 EP 4142 DI 10.1021/jm00100a019 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JW906 UT WOS:A1992JW90600019 PM 1433216 ER PT J AU JACOBSON, KA NIKODIJEVIC, O JI, XD BERKICH, DA EVELETH, D DEAN, RL HIRAMATSU, K KASSELL, NF VANGALEN, PJM LEE, KS BARTUS, RT DALY, JW LANOUE, KF MAILLARD, M AF JACOBSON, KA NIKODIJEVIC, O JI, XD BERKICH, DA EVELETH, D DEAN, RL HIRAMATSU, K KASSELL, NF VANGALEN, PJM LEE, KS BARTUS, RT DALY, JW LANOUE, KF MAILLARD, M TI SYNTHESIS AND BIOLOGICAL-ACTIVITY OF N-6-(P-SULFOPHENYL)ALKYL AND N-6-SULFOALKYL DERIVATIVES OF ADENOSINE - WATER-SOLUBLE AND PERIPHERALLY SELECTIVE ADENOSINE AGONISTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RAT HIPPOCAMPUS; A1-ADENOSINE RECEPTOR; ADENYLATE-CYCLASE; ANALOGS; ANTAGONISTS; DEPRESSION; A2-RECEPTORS; INHIBITION; RESPONSES; BINDING AB A series of N6-(p-sulfophenyl)alkyl and N6-sulfoalkyl derivatives of adenosine was synthesized, revealing that N6-(p-sulfophenyl)adenosine (10b) is a moderately potent (K(i) vs [H-3]PIA in rat cortical membranes was 74 nM) and A1-selective (120-fold) adenosine agonist, of exceptional aqueous solubility of >1.5 g/mL (almost-equal-to 3 M). Compound 10b was very potent in inhibiting synaptic potentials in gerbil hippocampal slices with an IC50 of 63 nM. At a dose of 0.1 mg/kg ip in rats, 10b inhibited lipolysis (a peripheral A1 effect) by 85% after 1 h. This in vivo effect was reversed using the peripherally selective A1-antagonist 1,3-dipropyl-8-[p-(carboxyethynyl)phenyl]xanthine (BW1433). The same dose of 10b in NIH Swiss mice (ip) was nearly inactive in locomotor depression, an effect that has been shown to be centrally mediated when elicited by lower doses of other potent adenosine agonists, such as N6-cyclohexyladenosine (CHA) (Nikodijevic et al. FEBS Lett. 1990, 261, 67). HPLC studies of biodistribution of a closely related and less potent homologue, N6-[4-(p-sulfophenyl)butyl]adenosine indicated that a 25 mg/kg ip dose in mice resulted in a plasma concentration after 30 min of 0.46 mug/mL and no detectable drug in the brain (detection limit <0.1% of plasma level). Although 10b at doses >0.1 mg/kg in mice depressed locomotor activity, this depression was unlike the effects of CHA and was reversible by BW1433. These data suggest that 10b is a potent adenosine agonist in vivo and shows poor CNS penetration. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033. CORTEX PHARMACEUT INC,IRVINE,CA 92718. UNIV VIRGINIA,DEPT NEUROSURG,CHARLOTTESVILLE,VA 22908. RP JACOBSON, KA (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8A,RM B1A-17,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 33 TC 44 Z9 45 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 30 PY 1992 VL 35 IS 22 BP 4143 EP 4149 DI 10.1021/jm00100a020 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA JW906 UT WOS:A1992JW90600020 PM 1433217 ER PT J AU DUMBACHER, JP BEEHLER, BM SPANDE, TF GARRAFFO, HM AF DUMBACHER, JP BEEHLER, BM SPANDE, TF GARRAFFO, HM TI HOMOBATRACHOTOXIN IN THE GENUS PITOHUI - CHEMICAL DEFENSE IN BIRDS SO SCIENCE LA English DT Article ID COLORATION AB Three passerine species in the genus Pitohui, endemic to the New Guinea subregion, contain the steroidal alkaloid homobatrachotoxin, apparently as a chemical defense. Toxin concentrations varied among species but were always highest in the skin and feathers. Homobatrachotoxin is a member of a class of compounds collectively called batrachotoxins that were previously considered to be restricted to neotropical poison-dart frogs of the genus Phyllobates. The occurrence of homobatrachotoxin in pitohuis suggests that birds and frogs independently evolved this class of alkaloids. C1 SMITHSONIAN INST,WILDLIFE CONSERVAT INT CONSERVAT INT,DIV BIRDS,WASHINGTON,DC 20560. NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP DUMBACHER, JP (reprint author), UNIV CHICAGO,DEPT ECOL & EVOLUT,CHICAGO,IL 60637, USA. NR 10 TC 133 Z9 140 U1 4 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 30 PY 1992 VL 258 IS 5083 BP 799 EP 801 DI 10.1126/science.1439786 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JV692 UT WOS:A1992JV69200037 PM 1439786 ER PT J AU GOLDFARB, LG PETERSEN, RB TABATON, M BROWN, P LEBLANC, AC MONTAGNA, P CORTELLI, P JULIEN, J VITAL, C PENDELBURY, WW HALTIA, M WILLS, PR HAUW, JJ MCKEEVER, PE MONARI, L SCHRANK, B SWERGOLD, GD AUTILIOGAMBETTI, L GAJDUSEK, DC LUGARESI, E GAMBETTI, P AF GOLDFARB, LG PETERSEN, RB TABATON, M BROWN, P LEBLANC, AC MONTAGNA, P CORTELLI, P JULIEN, J VITAL, C PENDELBURY, WW HALTIA, M WILLS, PR HAUW, JJ MCKEEVER, PE MONARI, L SCHRANK, B SWERGOLD, GD AUTILIOGAMBETTI, L GAJDUSEK, DC LUGARESI, E GAMBETTI, P TI FATAL FAMILIAL INSOMNIA AND FAMILIAL CREUTZFELDT-JAKOB DISEASE - DISEASE PHENOTYPE DETERMINED BY A DNA POLYMORPHISM SO SCIENCE LA English DT Article ID PRECURSOR PROTEIN GENE; HUMAN PRION PROTEIN; ALZHEIMERS-DISEASE; SPONGIFORM ENCEPHALOPATHY; SICKLING HEMOGLOBIN; MUTATION; BIOLOGY; VARIANT AB Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD), two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asn178) of the prion protein gene. The possibility that a second genetic component modified the phenotypic expression of the Asn178 mutation was investigated. FFI and the familial CJD subtype segregated with different genotypes determined by the Asn178 mutation and the methionine-valine polymorphism at codon 129. The Met129, Asn178 allele segregated with FFI in all 15 affected members of five kindreds whereas the Val129, Asn178 allele segregated with the familial CJD subtype in all 15 affected members of six kindreds. Thus, two distinct disease phenotypes linked to a single pathogenic mutation can be determined by a common polymorphism. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,DIV NEUROPATHOL,CLEVELAND,OH 44106. NINCDS,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV BOLOGNA,INST NEUROL,I-40126 BOLOGNA,ITALY. UNIV BORDEAUX,SCH MED,DEPT NEUROL,BORDEAUX,FRANCE. UNIV BORDEAUX,SCH MED,DEPT PATHOL,BORDEAUX,FRANCE. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. UNIV HELSINKI,DEPT PATHOL,SF-00100 HELSINKI 10,FINLAND. UNIV AUCKLAND,DEPT PHYS,AUCKLAND,NEW ZEALAND. LAB NEUROPATHOL R ESCOUROLLE,PARIS,FRANCE. UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48104. WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110. RI Petersen, Robert/B-5075-2011; Wills, Peter/B-9611-2012; OI Petersen, Robert/0000-0002-3154-0072; Wills, Peter/0000-0002-2670-7624; Cortelli, Pietro/0000-0002-3633-8818 FU NIA NIH HHS [1 R01 AGNS08155-02, AG-08012-02]; NINDS NIH HHS [NS 14509-13] NR 40 TC 528 Z9 533 U1 6 U2 41 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 30 PY 1992 VL 258 IS 5083 BP 806 EP 808 DI 10.1126/science.1439789 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JV692 UT WOS:A1992JV69200040 PM 1439789 ER PT J AU PRABHU, VV CLAVERIE, JM AF PRABHU, VV CLAVERIE, JM TI CORRELATIONS IN INTRONLESS DNA SO NATURE LA English DT Letter RP PRABHU, VV (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 4 TC 72 Z9 75 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 29 PY 1992 VL 359 IS 6398 BP 782 EP 782 DI 10.1038/359782a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JV777 UT WOS:A1992JV77700040 PM 1436053 ER PT J AU MAHAFFEY, KR AF MAHAFFEY, KR TI EXPOSURE TO LEAD IN CHILDHOOD - THE IMPORTANCE OF PREVENTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP MAHAFFEY, KR (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 11 TC 16 Z9 16 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 29 PY 1992 VL 327 IS 18 BP 1308 EP 1309 DI 10.1056/NEJM199210293271811 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JV259 UT WOS:A1992JV25900011 PM 1406822 ER PT J AU AGRAWAL, S TANG, JY SUN, D SARIN, PS ZAMECNIK, PC AF AGRAWAL, S TANG, JY SUN, D SARIN, PS ZAMECNIK, PC TI SYNTHESIS AND ANTI-HIV ACTIVITY OF OLIGORIBONUCLEOTIDES AND THEIR PHOSPHOROTHIOATE ANALOGS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; CHRONICALLY INFECTED-CELLS; ANTISENSE OLIGODEOXYNUCLEOTIDES; VIRAL-RNA; INHIBITION; REPLICATION; OLIGONUCLEOTIDES; EXPRESSION C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT BIOCHEM,WASHINGTON,DC 20037. RP AGRAWAL, S (reprint author), WORCESTER FDN EXPTL BIOL INC,222 MAPLE AVE,SHREWSBURY,MA 01545, USA. NR 17 TC 9 Z9 9 U1 0 U2 1 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 OCT 28 PY 1992 VL 660 BP 2 EP 10 DI 10.1111/j.1749-6632.1992.tb21052.x PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KG174 UT WOS:A1992KG17400001 PM 1340121 ER PT J AU NECKERS, L ROSOLEN, A FAHMY, B WHITESELL, L AF NECKERS, L ROSOLEN, A FAHMY, B WHITESELL, L TI SPECIFIC-INHIBITION OF ONCOGENE EXPRESSION INVITRO AND INVIVO BY ANTISENSE OLIGONUCLEOTIDES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID HUMAN NEURO-BLASTOMA; MYC-FAMILY GENES; DIFFERENTIAL EXPRESSION; TRANSGENIC MICE; CELLS; INJECTION; PRODUCT RP NECKERS, L (reprint author), NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 6 Z9 6 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 OCT 28 PY 1992 VL 660 BP 37 EP 44 DI 10.1111/j.1749-6632.1992.tb21055.x PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KG174 UT WOS:A1992KG17400004 PM 1340154 ER PT J AU MERCER, WE ULLRICH, SJ SHIELDS, MT LIN, D ALDER, H AF MERCER, WE ULLRICH, SJ SHIELDS, MT LIN, D ALDER, H TI CELL-CYCLE EFFECTS OF MICROINJECTED ANTISENSE OLIGODEOXYNUCLEOTIDES TO P34CDC2 KINASE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID DNA-REPLICATION; PROTEIN-KINASE; EXPRESSION; CDC2; PHOSPHORYLATION; PROLIFERATION; INHIBITION; HOMOLOG; MITOSIS; LINE C1 THOMAS JEFFERSON UNIV,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP MERCER, WE (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,609A BLUEMLE LIFE SCI BLDG,233 S 10TH ST,PHILADELPHIA,PA 19107, USA. FU NCI NIH HHS [CA 09644] NR 24 TC 6 Z9 6 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 OCT 28 PY 1992 VL 660 BP 209 EP 218 DI 10.1111/j.1749-6632.1992.tb21073.x PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KG174 UT WOS:A1992KG17400022 PM 1340123 ER PT J AU CASASFINET, JR KUMAR, A KARPEL, RL WILSON, SH AF CASASFINET, JR KUMAR, A KARPEL, RL WILSON, SH TI MAMMALIAN DNA POLYMERASE-BETA - CHARACTERIZATION OF A 16-KDA TRANSDOMAIN FRAGMENT CONTAINING THE NUCLEIC ACID-BINDING ACTIVITIES OF THE NATIVE ENZYME SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; PRIMER BINDING; IDENTIFICATION; PROTEINS; EXPRESSION; DOMAIN; REGION AB The 39-kDa DNA polymerase beta (beta-Pol) molecule can be readily converted into two constituent domains by mild proteolysis; these domains are represented in an 8-kDa N-terminal fragment and a 31-kDa C-terminal fragment [Kumar et al. (1990a) J. Biol. Chem. 265, 2124-2131]. Intact beta-Pol is a sequence-nonspecific nucleic acid-interactive protein that binds both double-stranded (ds) and single-stranded (ss) polynucleotides. These two activities appear to be contributed by separate portions of the enzyme, since the 31-kDa domain binds ds DNA but not ss DNA, and conversely, the 8-kDa domain binds ss DNA but not ds DNA [Casas-Finet et al. (1991) J. Biol. Chem. 266, 19618-19625]. Truncation of the 31-kDa domain at the N-terminus with chymotrypsin, to produce a 27-kDa fragment (residues 140-334), eliminated all DNA-binding activity. This suggested that the ds DNA-binding capacity of the 31-kDa domain may be carried in the N-terminal segment of the 31-kDa domain. We used CNBr to prepare a 16-kDa fragment (residues 18-154) that spans the ss DNA-binding region of the 8-kDa domain along with the N-terminal portion of the 31-kDa domain. The purified 16-kDa fragment was found to have both ss and ds polynucleotide-binding capacity. Thermodynamic binding properties for these activities are similar to those of the intact enzyme. The results indicate that all of the nucleic acid-binding capacity of beta-Pol is carried in the first 154 residues and permit localization of the ss- and ds-binding capacities, respectively, to contiguous segments within this region of the protein. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,CATONSVILLE,MD 21228. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 20 TC 26 Z9 27 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 OCT 27 PY 1992 VL 31 IS 42 BP 10272 EP 10280 DI 10.1021/bi00157a014 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV258 UT WOS:A1992JV25800014 PM 1420147 ER PT J AU RAO, PV ZIGLER, JS AF RAO, PV ZIGLER, JS TI PURIFICATION AND CHARACTERIZATION OF ZETA-CRYSTALLIN QUINONE REDUCTASE FROM GUINEA-PIG LIVER SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE ZETA-CRYSTALLIN; ENZYME CRYSTALLIN; QUINONE REDUCTASE; LENS; (GUINEA PIG LIVER) ID PLANAR AROMATIC-COMPOUNDS; INDUCIBLE EXPRESSION; LENS PROTEIN; GENE; DEHYDROGENASES; IDENTIFICATION; FAMILY AB Zeta-Crystallin, a major lens protein of certain mammalian species, has recently been characterized as a novel and active NADPH: quinone oxidoreductase. Here we report the purification of this protein from guinea pig liver by utilizing sequentially: ammonium sulphate precipitation, Blue Sepharose affinity, cation exchange and hydrophobic chromatography steps. This four-step isolation procedure yielded 118-fold purification and a specific activity of 6 U/mg protein when assayed in the presence of 9,10-phenanthrenequinone. Kinetic, immunological and physical properties of this protein have been found to be identical with those of guinea pig lens zeta-crystallin. Western blot analysis using antibodies raised against zeta-crystallin peptides demonstrated the presence of substantial amounts of this protein in human liver homogenates. C1 NEI,MECHANISMS OCULAR DIS LAB,BLDG 6,ROOM 237,BETHESDA,MD 20892. NR 20 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD OCT 27 PY 1992 VL 1117 IS 3 BP 315 EP 320 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JV936 UT WOS:A1992JV93600012 PM 1420281 ER PT J AU SCHOCH, C BLUMENTHAL, R CLAGUE, MJ AF SCHOCH, C BLUMENTHAL, R CLAGUE, MJ TI A LONG-LIVED STATE FOR INFLUENZA-VIRUS ERYTHROCYTE COMPLEXES COMMITTED TO FUSION AT NEUTRAL PH SO FEBS LETTERS LA English DT Article DE INFLUENZA HEMAGGLUTININ; MEMBRANE FUSION; OCTADECYL RHODAMINE ID ACTIVATED MEMBRANE-FUSION; STOPPED-FLOW MEASUREMENTS; HEMAGGLUTININ; CELLS; FLUORESCENCE; KINETICS AB The low pH-induced fusion of influenza virus with intact erythrocyte plasma membranes is preceded by a delay time following pH reduction, that is itself pH- and temperature dependent. At 37-degrees-C/pH 4.8, lipid mixing between virus and target membranes begins < 2 s after pH reduction, whereas at 4-degrees-C/pH 4.8, fusion does not commence until > 10 min after pH reduction. We have found that within this time period at 4-degrees-C, a population of virus acquires the capacity to subsequently undergo fusion with high efficiency at elevated temperatures and pH 7.4. Both the kinetics and the extent of this pH 7.4 fusion depend upon the time of pre-incubation at pH 4.8/4-degrees-C. Incubation at pH 7.4/4-degrees-C, following this pre-incubation does not result in fusion, but the capacity to fuse at pH 7.4/37-degrees-C is retained for a time period exceeding 1 h. The longevity of this fusion committed state makes it amenable to biochemical and immunological analysis. We have shown that it is insensitive to dithiothreitol, neuraminidase and trypsin, but is incapacitated by thermolysin or protease K. We conclude that only the HA2 sub-unit of influenza haemagglutinin is a necessary protein component of later stages of the fusion pathway. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. OI Clague, Michael/0000-0003-3355-9479 NR 17 TC 44 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 26 PY 1992 VL 311 IS 3 BP 221 EP 225 DI 10.1016/0014-5793(92)81107-W PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JU879 UT WOS:A1992JU87900010 PM 1397318 ER PT J AU SEKIGUCHI, M WADA, K WENTHOLD, RJ AF SEKIGUCHI, M WADA, K WENTHOLD, RJ TI N-ACETYLASPARTYLGLUTAMATE ACTS AS AN AGONIST UPON HOMOMERIC NMDA RECEPTOR (NMDAR1) EXPRESSED IN XENOPUS OOCYTES SO FEBS LETTERS LA English DT Article DE N-ACETYLASPARTYLGLUTAMATE; NMDA RECEPTOR; AMPA-SELECTIVE GLUTAMATE RECEPTOR; KAINATE RECEPTOR; XENOPUS OOCYTE; AGONIST ID PIG CEREBELLAR SLICES; SPINAL-CORD NEURONS; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; EXCITATORY ACTION; PURKINJE-CELLS; GLUTAMATE; SUBUNIT; FAMILY; BRAIN AB The electrophysiological effects of N-acetylaspartylglutamate (NAAG), an endogenous peptide restrictively distributed in the central nervous system, were studied using Xenopus oocytes injected with RNAs transcribed from cloned glutamate receptor cDNAs. NAAG induced an inward current, dose dependently, in oocytes injected with RNA for an N-methyl-D-aspartate receptor subunit (NMDAR1). In contrast, the oocytes injected with RNAs for AMPA-selective glutamate receptors (GluR1, GluR3, GluR1+GluR2 and GluR2+GluR3) scarcely responded to NAAG, and the oocytes injected with RNA for kainate receptor (GluR6) did not respond to NAAG. The half-maximal response (ED50) value of NAAG on expressed NMDAR1 was 185 muM, which shows that NAAG is about 115-times less potent than L-glutamate (Glu), the ED50 of which value was 1.6 muM. The maximal current amplitude induced by NAAG was about 70% of that by Glu. NAAG-induced current in NMDAR1-injected oocytes was potentiated by glycine, dose-dependently antagonized by DL-2-amino-5-phosphonovaleric acid, and blocked by magnesium ions in a voltage-dependent fashion. These results suggest that NAAG is one of the endogenous agonists selective for NMDAR1. RP SEKIGUCHI, M (reprint author), NIDOCD,NEUROCHEM LAB,BLDG 36,ROOM 5D08,BETHESDA,MD 20892, USA. NR 28 TC 57 Z9 58 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 26 PY 1992 VL 311 IS 3 BP 285 EP 289 DI 10.1016/0014-5793(92)81121-2 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JU879 UT WOS:A1992JU87900024 PM 1356833 ER PT J AU WHITE, LR AF WHITE, LR TI TOWARDS A PROGRAM OF CROSS-CULTURAL RESEARCH ON THE EPIDEMIOLOGY OF ALZHEIMERS-DISEASE SO CURRENT SCIENCE LA English DT Article ID MINI-MENTAL STATE; AT-ONSET PATTERNS; CLINICAL-DIAGNOSIS; COGNITIVE DECLINE; DRINKING-WATER; GMS-AGECAT; DEMENTIA; PREVALENCE; POPULATION; COMMUNITY AB Cross-cultural and international comparisons may illuminate how Alzheimer's disease and other major dementing illnesses are influenced by environmental, cultural, societal, and genetic factors. The meaning and value of such comparisons depends upon the care with which the studies are conducted, the use of cross-nationally standardized methods and criteria, and a great sensitivity to how culture, language, and education determine illness recognition, diagnosis, migration, and survival. RP WHITE, LR (reprint author), NIA,ASIA PACIFIC OFF,EPIDEMIOL DEMOG & BIOMET PROGRAM,BETHESDA,MD 20892, USA. NR 86 TC 21 Z9 21 U1 2 U2 4 PU CURRENT SCIENCE ASSN PI BANGALORE PA C V RAMAN AVENUE, PO BOX 8005, BANGALORE 560 080, INDIA SN 0011-3891 J9 CURR SCI INDIA JI Curr. Sci. PD OCT 25 PY 1992 VL 63 IS 8 BP 456 EP 469 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY308 UT WOS:A1992JY30800009 ER PT J AU MIZUUCHI, K AF MIZUUCHI, K TI POLYNUCLEOTIDYL TRANSFER-REACTIONS IN TRANSPOSITIONAL DNA RECOMBINATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID PHAGE-MU TRANSPOSASE; STRAND TRANSFER; BACTERIOPHAGE-MU; RETROVIRAL DNA; B-PROTEIN; TETRAHYMENA RIBOZYME; TN10 TRANSPOSITION; TARGET SITE; VIRAL-DNA; INTEGRATION RP MIZUUCHI, K (reprint author), NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 56 TC 114 Z9 114 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1992 VL 267 IS 30 BP 21273 EP 21276 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV011 UT WOS:A1992JV01100001 PM 1383220 ER PT J AU REINHART, J MERTZ, LM CATT, KJ AF REINHART, J MERTZ, LM CATT, KJ TI MOLECULAR-CLONING AND EXPRESSION OF CDNA-ENCODING THE MURINE GONADOTROPIN-RELEASING-HORMONE RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID LUTEINIZING-HORMONE; PITUITARY GONADOTROPHS; CELL-LINES; PROTEIN; MEMBRANE; BINDING; SITES; LOCALIZATION; METABOLISM; RESPONSES AB The primary structure of the gonadotropin-releasing hormone (GnRH) receptor was determined by sequencing a functional receptor cDNA isolated by expression cloning from an immortalized murine gonadotroph (alphaT3) cell line. Positive clone pools from a cDNA library were detected by screening expressed RNA in aequorin-injected Xenopus laevis oocytes, in which receptor-mediated calcium responses were monitored as light emission during stimulation by GnRH. The isolated receptor cDNA encodes a 327-amino acid protein that has seven putative transmembrane regions and is unique among G protein-coupled receptors in that the predicted sequence lacks a carboxyl-terminal cytoplasmic domain. COS-7 cells transfected with the receptor cDNA expressed high affinity binding sites for GnRH and its agonist and antagonist analogs and exhibited calcium responses to GnRH stimulation. These, and the prominent calcium responses of Xenopus oocytes injected with receptor RNA, were inhibited by GnRH antagonists. Northern blot analysis revealed two mRNAs (1.6 and 3.5 kilobases) in alphaT3 cells and in the mouse pituitary gland, and both transcripts were shown to encode functional GnRH receptors when expressed in Xenopus oocytes. In contrast, a single 4.6-kilobase receptor mRNA was present in rat anterior pituitary gland, ovary, and Leydig cells. The absence of a carboxyl-terminal cytoplasmic domain indicates the importance of other regions of the GnRH receptor in agonist-induced signal transduction, and possibly in receptor desensitization and sequestration. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BLDG 10, RM B1-L400, BETHESDA, MD 20892 USA. NR 50 TC 223 Z9 224 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1992 VL 267 IS 30 BP 21281 EP 21284 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV011 UT WOS:A1992JV01100003 PM 1328228 ER PT J AU OLIVER, KG PUTNEY, JW OBIE, JF SHEARS, SB AF OLIVER, KG PUTNEY, JW OBIE, JF SHEARS, SB TI THE INTERCONVERSION OF INOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE AND INOSITOL TETRAKISPHOSPHATES IN AR4-2J CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADRENAL GLOMERULOSA CELLS; LARGE INTESTINAL CANCER; MYOINOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE; 1,4,5-TRISPHOSPHATE 3-KINASE; RECEPTOR ACTIVATION; PANCREATOMA CELLS; PAROTID-GLAND; F344 RATS; METABOLISM; PENTAKISPHOSPHATE AB Data from several cell types have indicated that activation of hormone receptors promotes the metabolism of inositol 1,3,4,5,6-pentakisphosphate (IP5) to inositol 3,4,5,6-tetrakisphosphate ((3,4,5,6)IP4). However, to date, metabolism of IP5 by cell-free preparations has resulted in the formation of only inositol 1,4,5,6-tetrakisphosphate ((1,4,5,6)IP4). Thus, the metabolic relationships of IP5 with various inositol tetrakisphosphate (IP4) isomers have been investigated in both intact cells and cell homogenates of the rat pancreatoma cell line, AR4-2J. The steady-state concentration of IP5 was estimated to be 65 muM, while the combined concentration of (3,4,5,6)IP4 and (1,4,5,6)IP4 was approximately 1.0 muM. AR4-2J cell homogenates converted (1,3,4,6)IP4, (3,4,5,6)IP4, and (1,4,5,6)IP4 to IP5. (1,4,5,6)IP4 previously has not been demonstrated to be a precursor of IP5. To alter steady-state levels of inositol phosphates that were maintained by phosphorylation-dephosphorylation cycles, intact cells were treated with 10 muM antimycin A which reduced ATP levels by >90% within 10 min. Following 2 h of treatment with antimycin A, there was a 6-fold increase in both (3,4,5,6)IP4 and (1,4,5,6)IP4, presumably derived from IP5. Experiments with cell-free systems determined that IP5 was dephosphorylated to (1,4,5,6)IP4 by a predominantly particulate Mg2+-independent, Li+-insensitive IP5 3-phosphatase. However, in the presence of 5 mM MgATP, IP5 also was metabolized to (3,4,5,6)IP4. Therefore, our data demonstrate novel and complex relationships between IP5, (3,4,5,6)IP4, and (1,4,5,6)IP4. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. RP OLIVER, KG (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1992 VL 267 IS 30 BP 21528 EP 21534 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV011 UT WOS:A1992JV01100043 PM 1328236 ER PT J AU PAULAIS, M TURNER, RJ AF PAULAIS, M TURNER, RJ TI ACTIVATION OF THE NA+-K+-2CL- COTRANSPORTER IN RAT PAROTID ACINAR-CELLS BY ALUMINUM FLUORIDE AND PHOSPHATASE INHIBITORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OKADAIC ACID; PROTEIN PHOSPHATASES; CELLULAR-REGULATION; NA+/H+ EXCHANGE; SECRETION; CALCIUM; BINDING; TISSUES; VOLUME; CL AB The bumetanide-sensitive component of pH(i) recovery from an NH4Cl-induced acute alkaline load was used as a measure of Na+-K+-2Cl- cotransport activity in rat parotid acini. Acinar treatment with NaF/AlCl3 (15 mM NaF plus 10 muM AlCl3) induced a 5-fold stimulation in the initial rate of bumetanide-sensitive pH(i) recovery. This effect was dependent on NaF concentration (K1/2 almost-equal-to 7 mM) and was blunted in the presence of the Al3+ chelator desferal mesylate suggesting that it might be due to the aluminofluoride ion, AlF4-. NaF/AlCl3 treatment did not increase acinar intracellular cAMP levels but did result in an increase in intracellular calcium concentration (from 87 +/- 5 to 181 +/- 2 nM) and in acinar cell shrinkage (12 +/- 1 %). But the stimulation of the Na+-K+-2Cl- cotransporter by NaF/AlCl3 persisted in acini which had been depleted of their intracellular Ca2+ stores. In these acini no effect of NaF/AlCl3 on intracellular calcium or cell volume was observed, indicating that stimulation of the cotransporter was not secondary to either of these phenomena. The effect of NaF/AlCl3 on the cotransporter was blocked by the protein kinase inhibitor K252a indicating the involvement of a protein phosphorylation event. This result is consistent with either NaF/AlCl3-dependent protein kinase activation or phosphatase inhibition. The stimulation of the cotransporter by NaF/AlCl3 was mimicked by the protein phosphatase inhibitor calyculin A; however, this effect was not blocked by K252a suggesting that a different protein kinase from that associated with NaF/AlCl3 may be involved. The data indicate that the Na+-K+-2Cl- cotransporter in this tissue is under tight regulatory control, in all likelihood via multiple protein kinase/phosphatase systems. The physiological roles of these regulatory events in modulating acinar fluid secretion driven by the Na+-K+-2Cl-cotransporter remain to be elucidated. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1A06,BETHESDA,MD 20892. RI Paulais, Marc/E-5623-2017 NR 36 TC 39 Z9 39 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1992 VL 267 IS 30 BP 21558 EP 21563 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV011 UT WOS:A1992JV01100047 PM 1383225 ER PT J AU WIEDERRECHT, G HUNG, S CHAN, HK MARCY, A MARTIN, M CALAYCAY, J BOULTON, D SIGAL, N KINCAID, RL SIEKIERKA, JJ AF WIEDERRECHT, G HUNG, S CHAN, HK MARCY, A MARTIN, M CALAYCAY, J BOULTON, D SIGAL, N KINCAID, RL SIEKIERKA, JJ TI CHARACTERIZATION OF HIGH-MOLECULAR-WEIGHT FK-506 BINDING ACTIVITIES REVEALS A NOVEL FK-506-BINDING PROTEIN AS WELL AS A PROTEIN COMPLEX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CIS-TRANS ISOMERASE; PEPTIDYL-PROLYL ISOMERASE; T-CELL ACTIVATION; CYCLOSPORINE-A; IMMUNOSUPPRESSANT FK506; CALMODULIN-BINDING; LIMITED PROTEOLYSIS; MACROLIDES FK-506; CYCLOPHILIN; DISTINCT AB The immunoregulant FK-506 potently inhibits particular calcium-associated signal transduction events that occur early during T-lymphocyte activation and during IgE receptor-mediated exocytosis in mast cells. FK-506 binds to a growing family of receptors termed FK-506-binding proteins (FKBPs), the most abundant being a 12-kDa cytosolic receptor, FKBP12. To date, there is no formal evidence proving that FKBP12 is the sole receptor mediating the immunosuppressive effects or toxic side effects of FK-506. Using gel filtration chromatography as an assay for novel FK-506-binding proteins, we identified FK-506 binding activities in extracts prepared from calf brain and from JURKAT cells. Both of these new activities comigrated with apparent molecular masses of 1 10 kDa. However, further characterization of both binding activities revealed that the two are not identical. The 110-kDa activity observed in brain extracts appears to be the FKBP12.FK-506.calcineurin (CaN) complex previously reported (Liu, J., Farmer, J., Lane, W., Friedman, J., Weissman, I., and Schreiber, S. (1991) Cell 66, 807-815) while the 110 kDa activity observed in JURKAT cells is a novel FK-506-binding protein. Our characterization of the FKBP12.FK-506.CaN complex reveals a dependence upon calmodulin (CaM) for formation of the complex and demonstrates that the peptidyl-prolyl cis-trans isomerase (PPIase) activity of FKBP12 is not required for binding of FKBP12.FK-506 to CaN or for inhibition of CaN phosphatase activity. The novel FK-506-binding protein in JURKAT cells has been purified to homogeneity, migrates with an apparent mass of 51 kDa on denaturing gels, and has been termed FKBP51. Like FKBP12, FKBP51 has PPIase activity, but, unlike FKBP12.FK-506, FKBP51.FK-506 does not complex with or inhibit the phosphatase activity of, CaN. These results indicate that complex formation with CaN may not be a general property of the FKBPs. Peptide sequencing reveals that FKBP51 may be similar, if not identical, to hsp56, a component of non-transformed steroid receptors. C1 MERCK SHARP & DOHME LTD,DEPT IMMUNOL RES,POB 2000,R80W-107,RAHWAY,NJ 07065. MERCK SHARP & DOHME LTD,DEPT BIOPHYS CHEM,RAHWAY,NJ 07065. MERCK SHARP & DOHME LTD,DEPT BIOCHEM & MOLEC PATHOL,RAHWAY,NJ 07065. NIAAA,MOLEC & CELLULAR NEUROBIOL,IMMUNOL SECT,ROCKVILLE,MD 20852. NR 44 TC 94 Z9 96 U1 1 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 OCT 25 PY 1992 VL 267 IS 30 BP 21753 EP 21760 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV011 UT WOS:A1992JV01100077 PM 1383226 ER PT J AU SAVARESE, DMF RUSSELL, JT FATATIS, A LIOTTA, LA AF SAVARESE, DMF RUSSELL, JT FATATIS, A LIOTTA, LA TI TYPE-IV COLLAGEN STIMULATES AN INCREASE IN INTRACELLULAR CALCIUM - POTENTIAL ROLE IN TUMOR-CELL MOTILITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-MELANOMA CELLS; INOSITOL TRISPHOSPHATE; EXTRACELLULAR-MATRIX; SIGNAL TRANSDUCTION; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; DICTYOSTELIUM-DISCOIDEUM; NEUTROPHIL CHEMOTAXIS; CYCLIC METABOLITE; PEPTIDE RECEPTOR; PLASMA-MEMBRANE AB Type IV collagen (Coll IV), a component of the extracellular matrix, stimulates motility in the A2058 human melanoma cell line, a response that is inhibited by pertussis toxin (PT). Fibronectin (FN)-induced chemotaxis in this cell line is not affected by PT. To understand the mechanism of cellular signaling, single cell intracellular Ca2+ responses to Coll IV and FN were studied using Fura-2 and digital imaging fluorescence microscopy. Coll IV, at a dose that stimulates motility (100 mug/ml, 185 nM), induces a significant rise in cytosolic free Ca2+ concentration ([Ca2+]i) within 100 s. This response is not inhibited by PT. Treatment of the cells with FN 30 mug/ml (70 nM), a dose that stimulates near-maximal chemotaxis, does not increase [Ca2+]i appreciably. Removal of extracellular Ca2+ fails to inhibit the Coll IV-stimulated rise in Ca2+ in all cells. Depletion of extracellular Ca2+ and pretreatment of cells with Ca2+ channel blockers only partially inhibits Coll IV-induced motility. Depletion of intracellular Ca2+ inhibits both chemotaxis and the Coll IV-induced increase in intracellular Ca2+. Coll IV does not stimulate membrane phosphoinositide hydrolysis. We conclude that Coll IV treatment induces an inositol 1,4,5-trisphosphate-independent release of intracellular Ca2+ stores which appears to play a necessary role in the chemotactic response of A2058 cells but is not mediated by a PT-sensitive G-protein. This response is not seen in cells exposed to FN, suggesting different intracellular signaling mechanisms for stimulated motility between these two extracellular matrix molecules. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. POLICLIN NAPLES 2,IST FARMACOL,NAPLES,ITALY. NR 52 TC 60 Z9 61 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1992 VL 267 IS 30 BP 21928 EP 21935 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV011 UT WOS:A1992JV01100103 PM 1328249 ER PT J AU ADACHI, Y COPELAND, TD TAKAHASHI, C NOSAKA, T AHMED, A OROSZLAN, S HATANAKA, M AF ADACHI, Y COPELAND, TD TAKAHASHI, C NOSAKA, T AHMED, A OROSZLAN, S HATANAKA, M TI PHOSPHORYLATION OF THE REX PROTEIN OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KINASE-C; HTLV-I; MESSENGER-RNA; STRUCTURAL PROTEINS; ACTIVATOR PROTEIN; GENE-PRODUCT; EXPRESSION; SEQUENCE; P40X; DNA AB Rex protein, the posttranscriptional regulator of human T-cell leukemia virus type I (HTLV-I), is required for the control of viral structural protein expression and virus replication. Rex is a phosphoprotein found predominantly in the cell nucleolus, whose function is thought to be regulated by its nucleolar localization and phosphorylation. Therefore, we investigated the in vivo phosphorylation of Rex protein in more detail. Phosphorylation of Rex occurred in all HTLV-I-infected cell lines examined in vivo, primarily at serine residues and to a very small extent at threonine residues. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) led to significant but transient enhancement of the incorporation of [P-32]orthophosphate into Rex protein. N-terminal truncation of Rex protein abolished TPA-dependent phosphorylation. Chymotryptic digestion of phosphorylated Rex yielded two phosphopeptides. In vivo phosphorylation sites were identified as serine residues 70 and 177 and threonine residue 174. Serine 70 was a TPA-dependent phosphorylation site within a regulatory domain. We have already shown that the protein kinase C inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine specifically blocked accumulation of viral unspliced gag-pol mRNA. Therefore, the phosphorylation at serine 70 may be involved in the regulation of Rex function in response to extracellular stimuli. C1 KYOTO UNIV, INST VIRUS RES, KYOTO 606, JAPAN. NCI, FREDERICK CANC RES & DEV CTR, BASIC RES PROGRAM, MOLEC VIROL & CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101] NR 45 TC 40 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1992 VL 267 IS 30 BP 21977 EP 21981 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV011 UT WOS:A1992JV01100110 PM 1400509 ER PT J AU SAXENA, SK RYBAK, SM DAVEY, RT YOULE, RJ ACKERMAN, EJ AF SAXENA, SK RYBAK, SM DAVEY, RT YOULE, RJ ACKERMAN, EJ TI ANGIOGENIN IS A CYTOTOXIC, TRANSFER RNA-SPECIFIC RIBONUCLEASE IN THE RNASE-A SUPERFAMILY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EOSINOPHIL-DERIVED NEUROTOXIN; AMINO-ACID SEQUENCE; FREE PROTEIN-SYNTHESIS; MAJOR BASIC-PROTEIN; XENOPUS OOCYTES; CATIONIC PROTEIN; RIBOSOMAL-RNA; ALPHA-SARCIN; TOXIN; INACTIVATION AB Angiogenin is a 14.4-kDa human plasma protein with 65% homology to RNase A that retains the key active site residues and three of the four RNase A disulfide bonds. We demonstrate that recombinant angiogenin functions as a cytotoxic tRNA-specific RNase in cell-free lysates and when injected into Xenopus oocytes. Inhibition of protein synthesis by angiogenin correlates with degradation of endogenous oocyte tRNA. Exogenous, radiolabeled tRNA is also hydrolyzed by angiogenin, whereas oocyte rRNA and mRNA are not detectably degraded by angiogenin. Protein synthesis was restored to angiogenin-injected oocytes by injecting the RNase inhibitor RNasin(TM) plus total Xenopus or calf liver tRNAs, thereby demonstrating that the tRNA degradation induced by angiogenin was the sole cause of cytotoxicity. A similar tRNA-reversible inhibition of protein synthesis was seen in rabbit reticulocyte lysates. Angiogenin therefore appears to be a specific cellular tRNase, whereas five homologues in the RNase A superfamily lack angiogenin's specificity for tRNA. One of these homologues purified from human eosinophils, eosinophil-derived neurotoxin, nonspecifically degrades oocyte RNA similar to RNase A and is also cytotoxic at very low concentrations. C1 NIDDKD,GENET & BIOCHEM BRANCH,BLDG 10,RM 9D15,BETHESDA,MD 20892. NINDB,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. OI Saxena, Shailendra K/0000-0003-2856-4185 FU PHS HHS [1-8325256] NR 38 TC 102 Z9 106 U1 1 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 OCT 25 PY 1992 VL 267 IS 30 BP 21982 EP 21986 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV011 UT WOS:A1992JV01100111 PM 1400510 ER PT J AU XUAN, JC WEBER, IT AF XUAN, JC WEBER, IT TI CRYSTAL-STRUCTURE OF A B-DNA DODECAMER CONTAINING INOSINE, D(CGCIAATTCGCG), AT 2.4 A RESOLUTION AND ITS COMPARISON WITH OTHER B-DNA DODECAMERS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BASE-PAIRS; POLYINOSINIC ACID; DOUBLE-HELIX; GEOMETRY; TRACT; DEOXYINOSINE; CONFORMATION; DECAMERS; DUPLEX; PROBE AB The crystal structure of the dodecamer, d(CGCIAATTCGCG), has been determined at 2.4 angstrom resolution by molecular replacement, and refined to an R-factor of 0.174. The structure is isomorphous with that of the B-DNA dodecamer, d(CGCGAATTCGCG), in space group P2(1)2(1)2(1) with cell dimensions of a = 24.9, b = 40.4, and c = 66.4 angstrom. The initial difference Fourier maps clearly indicated the presence of inosine instead of guanine. The structure was refined with 44 water molecules, and compared to the parent dodecamer. Overall the two structures are very similar, and the I:C forms Watson - Crick base pairs with similar hydrogen bond geometry to the G:C base pairs. The propeller twist angle is low for 14:C21 and relatively high for the 116:Cg base pair (-3.2-degrees compared to -23.0-degrees), and the buckle angles alter, probably due to differences in the contacts with symmetry related molecules in the crystal lattice. The central base pairs of d(CGCIAATTCGCG) show the large propeller twist angles, and the narrow minor groove that characterize A-tract DNA, although I:C base pairs cannot form the major groove bifurcated hydrogen bonds that are possible for A:T base pairs. C1 NCI,FREDERICK CANC RES FACIL,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT PHARMACOL,PHILADELPHIA,PA 19107. FU PHS HHS [N01-C01-74101] NR 29 TC 53 Z9 53 U1 0 U2 0 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 OCT 25 PY 1992 VL 20 IS 20 BP 5457 EP 5464 DI 10.1093/nar/20.20.5457 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW666 UT WOS:A1992JW66600027 PM 1437563 ER PT J AU CHANG, YN JEANG, KT AF CHANG, YN JEANG, KT TI THE BASIC RNA-BINDING DOMAIN OF HIV-2 TAT CONTRIBUTES TO PREFERENTIAL TRANSACTIVATION OF A TAR2-CONTAINING LTR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MUTATIONAL ANALYSIS; FUNCTIONAL DOMAINS; NASCENT RNA; PROTEIN; TYPE-1; TRANSACTIVATION; SEQUENCE; REGION; RECOGNITION AB Human immunodeficiency viruses HIV-1 and HIV-2 encode a Tat protein that trans-activates the respective viral genome through RNA targets (TAR1 and TAR2). Tat-1 and Tat-2 have considerable homology. However, an interesting biological observation has been that Tat-1 activates the HIV-1 and HIV-2 LTRs equally while Tat-2 activates the former, in comparison to the latter, poorly. Here, we present evidence that it is the TAR2 RNA target together with the basic RNA-binding protein domain of Tat-2 that dictate this non-reciprocity in trans-activation. C1 NIAID,MOLEC MICROBIOL LAB,BLDG 4,ROOM 30L,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 37 TC 26 Z9 27 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 OCT 25 PY 1992 VL 20 IS 20 BP 5465 EP 5472 DI 10.1093/nar/20.20.5465 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW666 UT WOS:A1992JW66600028 PM 1437564 ER PT J AU MILLER, RW AF MILLER, RW TI VITAMIN-K AND CHILDHOOD-CANCER SO BRITISH MEDICAL JOURNAL LA English DT Letter RP MILLER, RW (reprint author), NCI,CLIN EPIDEMIOL BRANCH,EPN-400,BETHESDA,MD 20892, USA. NR 4 TC 15 Z9 15 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD OCT 24 PY 1992 VL 305 IS 6860 BP 1016 EP 1016 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JV776 UT WOS:A1992JV77600056 PM 1458120 ER PT J AU PERSSON, I YUEN, J BERGKVIST, L ADAMI, HO HOOVER, R SCHAIRER, C AF PERSSON, I YUEN, J BERGKVIST, L ADAMI, HO HOOVER, R SCHAIRER, C TI COMBINED ESTROGEN-PROGESTOGEN REPLACEMENT AND BREAST-CANCER RISK SO LANCET LA English DT Letter C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP PERSSON, I (reprint author), UNIV HOSP UPPSALA,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. NR 2 TC 57 Z9 58 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD OCT 24 PY 1992 VL 340 IS 8826 BP 1044 EP 1044 DI 10.1016/0140-6736(92)93064-T PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JV014 UT WOS:A1992JV01400049 PM 1357438 ER PT J AU HE, XP LEE, PHK PENNYPACKER, KR TUOMINEN, RK MAR, EC THAI, L HONG, JS AF HE, XP LEE, PHK PENNYPACKER, KR TUOMINEN, RK MAR, EC THAI, L HONG, JS TI CHARACTERIZATION OF DYNORPHIN-CONTAINING NEURONS ON DISSOCIATED DENTATE GYRUS CELL-CULTURES SO BRAIN RESEARCH LA English DT Article DE HIPPOCAMPUS; NEURONAL CELL CULTURE; IMMUNOCYTOCHEMISTRY; DENTATE GRANULE CELL; DYNORPHIN; INSITU HYBRIDIZATION ID PRODYNORPHIN MESSENGER-RNA; RAT HIPPOCAMPUS; IMMUNOREACTIVE NEURONS; MOUSE HIPPOCAMPUS; SUBSTANCE-P; BRAIN; LOCALIZATION; ENKEPHALIN; CHOLECYSTOKININ; QUANTITATION AB In the dentate gyrus, the synthesis of the opioid peptide, dynorphin, is modulated by a variety of stimuli. In order to elucidate the cellular and molecular mechanisms regulating the synthesis of dynorphin in the hippocampus, we have established a routine primary cell culture of dentate granule neurons and identified granule-like neurons by a characteristic marker, dynorphin, in these cultures. Cultures were prepared from 7-day-old rat pups and maintained in medium with 2% fetal bovine serum. These cultures contained approximately 20% neurons and survived for over 4 weeks. After 2 weeks in culture, neurons expressing dynorphin-A and its messenger RNA were detected using immunocytochemistry and in situ hybridization, respectively. In dentate cultures, enkephalin-, cholecystokinin-, neuropeptide Y- and substance P-positive cells were observed in addition to dynorphin-positive cells with immunocytochemistry. The results suggest that dentate gyrus cell cultures provide a valid in vitro model for studying molecular mechanisms regulating prodynorphin gene expression. C1 NIEHS,NEUROPHARMACOL SECT,MOLEC & INTEGRAT NEUROSCI LAB,POB 12233,RES TRIANGLE PK,NC 27709. BURROUGHS WELLCOME CO,DIV CELL BIOL,RES TRIANGLE PK,NC 27709. UNIV HELSINKI,DEPT PHARMACOL,SF-00100 HELSINKI 10,FINLAND. RI Pennypacker, Keith/I-5092-2012 FU FIC NIH HHS [1 FO5 TWO4205-01 B1-5] NR 32 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 23 PY 1992 VL 594 IS 1 BP 91 EP 98 DI 10.1016/0006-8993(92)91032-A PG 8 WC Neurosciences SC Neurosciences & Neurology GA JW510 UT WOS:A1992JW51000010 PM 1361409 ER PT J AU WELLER, M MARINI, AM PAUL, SM AF WELLER, M MARINI, AM PAUL, SM TI NIACINAMIDE BLOCKS 3-ACETYLPYRIDINE TOXICITY OF CEREBELLAR GRANULE CELLS-INVITRO SO BRAIN RESEARCH LA English DT Note DE 3-ACETYLPYRIDINE; NIACINAMIDE; NEUROTOXICITY; CEREBELLAR GRANULE CELL ID RAT; NEUROTOXICITY; DEGENERATION; HARMALINE; SYSTEM AB 3-Acetylpyridine (3AP) is a potent neurotoxin when administered to laboratory animals. However, its neurotoxic effects have not been investigated extensively in vitro. Cultured cerebellar granule cells are killed by concentrations of 3AP of 0.1-1 mM (ED50 = 220 muM) but not by its 2-acetyl and 4-acetyl analogues. The toxicity of 3AP is enhanced by preexposure to subtoxic concentrations of N-methyl-D-aspartate (NMDA) and is unaffected by the NMDA receptor antagonists MK-801 or APV, as well as by deprenyl, mazindol, or tetrahydrofolic acid. However, 3AP toxicity is completely blocked by preincubating cerebellar granule cells with low concentrations of niacinamide. These data lead us to suggest that 3AP toxicity is due to the substitution of 3AP for niacinamide in the formation of niacinamide adenine dinucleotides (NAD(P)). C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BLDG 10,ROOM 4N224,BETHESDA,MD 20892. NR 17 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 23 PY 1992 VL 594 IS 1 BP 160 EP 164 DI 10.1016/0006-8993(92)91043-E PG 5 WC Neurosciences SC Neurosciences & Neurology GA JW510 UT WOS:A1992JW51000021 PM 1361407 ER EF