FN Thomson Reuters Web of Science™ VR 1.0 PT J AU KASLOW, DC ISAACS, SN QUAKYI, IA GWADZ, RW MOSS, B KEISTER, DB AF KASLOW, DC ISAACS, SN QUAKYI, IA GWADZ, RW MOSS, B KEISTER, DB TI INDUCTION OF PLASMODIUM-FALCIPARUM TRANSMISSION-BLOCKING ANTIBODIES BY RECOMBINANT VACCINIA VIRUS SO SCIENCE LA English DT Article ID SEXUAL STAGES; EXPRESSION; ANTIGENS; SURFACE AB Many candidate antigens of malaria vaccines have limited immunological recognition. One exception is Pfs25, a cysteine-rich, 25-kilodalton sexual stage surface protein of Plasmodium falciparum. Pfs25 is a target of monoclonal antibodies that block transmission of malaria from vertebrate host to mosquito vector. The surface of mammalian cells infected with a recombinant vaccinia virus that expressed Pfs25 specifically bound transmission-blocking monoclonal antibodies. Furthermore, major histocompatibility complex-disparate congenic mouse strains immunized with recombinant Pfs25 elicited transmission-blocking antibodies, demonstrating that the capacity to develop transmission-blocking antibodies is not genetically restricted in mice. Live recombinant viruses may provide an inexpensive, easily administered alternative to subunit vaccines prepared from purified recombinant proteins to block transmission of malaria in developing countries. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP KASLOW, DC (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 16 TC 64 Z9 65 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 31 PY 1991 VL 252 IS 5010 BP 1310 EP 1313 DI 10.1126/science.1925544 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FN857 UT WOS:A1991FN85700041 PM 1925544 ER PT J AU TSUTSUMI, K VISWANATHAN, M STROMBERG, C SAAVEDRA, JM AF TSUTSUMI, K VISWANATHAN, M STROMBERG, C SAAVEDRA, JM TI TYPE-1 AND TYPE-2 ANGIOTENSIN-II RECEPTORS IN FETAL-RAT BRAIN SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE BRAIN DEVELOPMENT; ANGIOTENSIN II RECEPTOR SUBTYPES; RENIN-ANGIOTENSIN SYSTEM; NUCLEUS-TRACTUS-SOLITARII (NTS); CHOROID PLEXUS; INFERIOR OLIVE ID GESTATION; SUBTYPES AB Brain angiotensin II receptors were located in 18-day-old rat embryos by quantitative autoradiography. In the nucleus of the solitary tract and choroid plexus, binding was displaced by the type-1 antagonist DuP 753. In the inferior olive, paratrigeminal and hypoglossal nuclei, binding was displaced by the type-2 antagonist CGP 42112 A. Meninges and cephalic soft tissues contained predominantly type-2 angiotensin II receptors. Our results indicate a role for type-1 and type-2 angiotensin II receptors during brain development. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D045,BETHESDA,MD 20892. NR 9 TC 65 Z9 65 U1 0 U2 0 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 MAY 30 PY 1991 VL 198 IS 1 BP 89 EP 92 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FT894 UT WOS:A1991FT89400013 PM 1717294 ER PT J AU CALVERT, I PENG, ZQ KUNG, HF RAZIUDDIN AF CALVERT, I PENG, ZQ KUNG, HF RAZIUDDIN TI CLONING AND CHARACTERIZATION OF A NOVEL SEQUENCE-SPECIFIC DNA-BINDING PROTEIN RECOGNIZING THE NEGATIVE REGULATORY ELEMENT (NRE) REGION OF THE HIV-1 LONG TERMINAL REPEAT SO GENE LA English DT Article DE RECOMBINANT DNA; AIDS; MURINE, RAT, AND HUMAN CELLS; TRANSCRIPTION FACTOR; PHAGE-LAMBDA LIBRARY ID TRANSCRIPTIONAL REGULATION; TRANS-ACTIVATOR; VIRUS; EXPRESSION; SP1 AB The present studies describe the isolation of a murine cDNA clone that encodes a novel DNA-binding protein recognizing the negative regulatory element (NRE) region of the HIV-1 long terminal repeat (LTR). This cDNA expresses a truncated protein with a functional DNA-binding domain, which is rich in glutamine/proline and serine/thereonine, a characteristic of a majority of sequence-specific DNA-binding proteins and transcriptional factors. The cDNA hybridizes to a single-copy gene that is expressed as an approx. 4.2-kb mRNA in a variety of murine and human cell types, implying that this gene is expressed in an ubiquitous fashion. The NRE region has been reported to down-regulate LTR-directed gene expression [Rosen et al., Cell 41 (1985) 813-823]. This is the first sequence-specific DNA-binding protein reported to recognize the NRE region. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21702. FU PHS HHS [N01-C0-74012] NR 22 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 30 PY 1991 VL 101 IS 2 BP 171 EP 176 DI 10.1016/0378-1119(91)90408-4 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA FV998 UT WOS:A1991FV99800002 PM 2055486 ER PT J AU BUIATTI, E PALLI, D BIANCHI, S DECARLI, A AMADORI, D AVELLINI, C CIPRIANI, F COCCO, P GIACOSA, A LORENZINI, L MARUBINI, E PUNTONI, R SARAGONI, A FRAUMENI, JF BLOT, WJ AF BUIATTI, E PALLI, D BIANCHI, S DECARLI, A AMADORI, D AVELLINI, C CIPRIANI, F COCCO, P GIACOSA, A LORENZINI, L MARUBINI, E PUNTONI, R SARAGONI, A FRAUMENI, JF BLOT, WJ TI A CASE-CONTROL STUDY OF GASTRIC-CANCER AND DIET IN ITALY .3. RISK PATTERNS BY HISTOLOGIC TYPE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID STOMACH-CANCER; HISTOPATHOLOGIC PATTERNS; DIFFUSE TYPES; TIME TRENDS; CARCINOMA; HAWAII; CLASSIFICATION; JAPANESE; AREA AB In a case-control study of gastric cancer (GC) in high-risk and low-risk areas of Italy, 923 GCs were systematically categorized by one pathologist according to the Lauren classification distinguishing 2 main histologic types, intestinal (55%) and diffuse (23%). Intestinal types outnumbered diffuse types by a 3 to 1 margin in high-risk regions in the north-central part of the country, while both types occurred at nearly equal rates in low-risk areas. Intestinal types also occurred relatively more frequently at older ages and among males. Relative risks of each type of GC were evaluated in relation to dietary and other data obtained from interviews with the cancer patients and controls. The risk patterns for intestinal and diffuse types were remarkably similar. Increased risks of both types were associated with high intake of meat, salted/dried fish, seasoned cheeses and traditional soups, while decreased risks of both types were found among heavy consumers of fresh vegetables and fruits. Correspondingly similar patterns were seen with indices of nutrients, with risks of both intestinal and diffuse GC rising with animal protein intake and declining with consumption of vitamins C and E. Both types were inversely related to socio-economic status, and neither was associated with cigarette smoking. A familial history of GC was reported more frequently by patients with each type than by controls, although the highest risk was for unclassified GC, a group of poorly differentiated and medullary carcinomas accounting for 15% of all GCs in this study. The findings suggest that, despite differences in geographic and demographic patterns, the intestinal and diffuse types of GC have etiologic factors in common. C1 UNIV FLORENCE,IST ANAT PATOL,I-50121 FLORENCE,ITALY. UNIV MILAN,IST STAT MED & BIOMETRIA,I-20122 MILAN,ITALY. IST NAZL TUMORI,I-20133 MILAN,ITALY. OSPED MORGAGNI PIERANTONI,SERV ONCOL,FORLI,ITALY. OSPED MORGAGNI PIERANTONI,SERV ANAT PATOL,FORLI,ITALY. OSPED IMOLA,SERV ANAT PATOL,IMOLA,ITALY. UNIV CAGLIARI,IST MED LAVORO,I-09100 CAGLIARI,ITALY. IST NAZL RIC CANC,GENOA,ITALY. UNIV SIENA,IST ANAT PATOL 2,I-53100 SIENA,ITALY. NCI,BETHESDA,MD 20892. RP BUIATTI, E (reprint author), CTR STUDIO PREVENZ ONCOL,UNITA EPIDEMIOL,VIALE VOLTA 171,I-50131 FLORENCE,ITALY. RI Decarli, Adriano/C-3129-2017 OI Decarli, Adriano/0000-0003-1451-8292 FU NCI NIH HHS [N01-CP-51019] NR 28 TC 71 Z9 71 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 30 PY 1991 VL 48 IS 3 BP 369 EP 374 DI 10.1002/ijc.2910480310 PG 6 WC Oncology SC Oncology GA FQ400 UT WOS:A1991FQ40000009 PM 2040530 ER PT J AU GUADAGNI, F TORTORA, G ROSELLI, M CLAIR, T CHOCHUNG, YS SCHLOM, J GREINER, JW AF GUADAGNI, F TORTORA, G ROSELLI, M CLAIR, T CHOCHUNG, YS SCHLOM, J GREINER, JW TI CARCINOEMBRYONIC ANTIGEN REGULATION IN HUMAN COLORECTAL TUMOR-CELLS BY A SITE-SELECTIVE CYCLIC-AMP ANALOG - A COMPARISON WITH INTERFERON-GAMMA SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID COLON CARCINOMA-CELLS; ADENOCARCINOMA CELLS; MONOCLONAL-ANTIBODIES; CANCER-CELLS; HUMAN-BREAST; EXPRESSION; MODULATION; PROTEIN; RELEASE; GROWTH AB Treatment of human colorectal tumor cells (LSI74T, HT29, and WiDr) with analogues of cyclic (cAMP) (dibutyryl-cAMP) and 8-CI-cAMP) selectively enhances the expression of carcinoembryonic antigen (CEA). Dose and temporal kinetics results revealed that 8-CI-cAMP was approximately 100-fold more potent than dibutyryl-cAMP for increasing CEA expression. Results demonstrated that 8-Cl-cAMP treatment of LS174T quantitatively increased CEA levels in cell extracts 2-fold, increased anti-CEA monoclonal antibody (MAb) binding to the tumor cell surface, and induced the appearance of CEA-related mRNA transcripts. The findings suggest that 8-Cl-cAMP is capable of regulating CEA expression at transcriptional and/or post-transcriptional levels. Other human tumor cells, as well as normal cell types which do not constitutively express CEA, remained CEA-negative following 8-Cl-cAMP treatment. Moreover, the level of expression of other human tumor antigens as well as antigens of the major histocompatibility complex were not changed by 8-Cl-cAMP treatment, suggesting some selectively for CEA regulation by this cAMP analogue. In vivo administration of 8-Cl-cAMP to athymic mice bearing LS174T tumor xenografts increased the amount of anti-CEA MAb bound to tumor extracts as well as the tumor localization of a radionuclide-conjugated anti-CEA MAb. The results indicate that 8-Cl-cAMP can selectively upregulate CEA expression on human colorectal tumor cells in vitro and in vivo. Interestingly, IFN-gamma treatment of the LS174T cells fails to enhance or induce expression of CEA or any of the histocompatibility leukocyte antigens. Thus, 8-Cl-cAMP treatment regulates CEA expression through another cellular pathway which may involve cAMP-dependent protein kinase. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. RI Guadagni, Fiorella/J-4432-2013 OI Guadagni, Fiorella/0000-0003-3652-0457 NR 37 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 30 PY 1991 VL 48 IS 3 BP 413 EP 422 DI 10.1002/ijc.2910480319 PG 10 WC Oncology SC Oncology GA FQ400 UT WOS:A1991FQ40000018 PM 1645700 ER PT J AU MACK, JW TORCHIA, DA AF MACK, JW TORCHIA, DA TI A H-2 NMR-STUDY OF THE MOLECULAR-DYNAMICS OF SOLID CYCLOPENTANE SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; SPIN-LATTICE RELAXATION; LINE-SHAPES; PSEUDOROTATION; AMPLITUDE; PROLINE; MOTION; STATE; RING AB We report models for the molecular motions of cyclopentane in its three solid phases, based upon analyses of equilibrium and partially relaxed H-2 NMR line shapes. At temperatures below -150-degrees-C, phase III, the spectrum of [H-2(10)]cyclopentane is a Pake pattern having a quadrupole coupling constant of 171 kHz. This observation together with the T1 value, 9.0 s, observed at -178-degrees-C, shows that molecular reorientation of the C-H-2 bonds is limited to small-amplitude picosecond motions in phase III. In contrast, in the -150 to -172-degrees-C range, in supercooled phase II, line shapes are axially asymmetric, order parameters are small (S2 ca. 0.01-0.05), and T1 values are 50-80 ms. The data indicate that fast-limit motion predominates in this phase, which is simulated by using jump models involving four sites, which we interpret as being due to a combination of pseudorotation and a rocking motion about the 5-fold molecular axis. In the temperature range -135 to -150-degrees-C, normal phase II, spectra lack fine structure and the line shape has a Lorentzian appearance. In the temperature range -97 to -135-degrees-C, phase I, the spectra are usually composed of a number of doublets, whose splittings depend upon the orientation of the sample relative to the external field, because in phase I the sample typically consists of a nonrandom distribution of crystallites. Occasionally a nearly random distribution of crystallites is obtained in phase I, based upon the observation of a nearly ideal Pake pattern. Throughout phase I the observed quadrupole splitting is less than 3 kHz, showing that cyclopentane reorientation in this phase is, in effect, nearly isotropic. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 36 TC 12 Z9 12 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD MAY 30 PY 1991 VL 95 IS 11 BP 4207 EP 4213 DI 10.1021/j100164a009 PG 7 WC Chemistry, Physical SC Chemistry GA FP241 UT WOS:A1991FP24100009 ER PT J AU HADLEY, SW AF HADLEY, SW TI SECRET SERVICE SO NATURE LA English DT Letter RP HADLEY, SW (reprint author), NCI,OFF SCI INTEGR,ROOM 207,BLDG 1,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 30 PY 1991 VL 351 IS 6325 BP 340 EP 340 DI 10.1038/351340c0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FN856 UT WOS:A1991FN85600016 ER PT J AU GALLO, RC AF GALLO, RC TI AND HIS RESPONSE SO NATURE LA English DT Letter RP GALLO, RC (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 30 PY 1991 VL 351 IS 6325 BP 358 EP 358 DI 10.1038/351358b0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FN856 UT WOS:A1991FN85600039 ER PT J AU REITZ, MS STREICHER, HZ GALLO, RC AF REITZ, MS STREICHER, HZ GALLO, RC TI GALLO VIRUS SEQUENCE SO NATURE LA English DT Letter ID NUCLEOTIDE-SEQUENCE; AIDS VIRUS RP REITZ, MS (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 30 PY 1991 VL 351 IS 6325 BP 358 EP 358 DI 10.1038/351358a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FN856 UT WOS:A1991FN85600038 PM 2034286 ER PT J AU COSSON, P LANKFORD, SP BONIFACINO, JS KLAUSNER, RD AF COSSON, P LANKFORD, SP BONIFACINO, JS KLAUSNER, RD TI MEMBRANE-PROTEIN ASSOCIATION BY POTENTIAL INTRAMEMBRANE CHARGE PAIRS SO NATURE LA English DT Article ID ANTIGEN RECEPTOR COMPLEX; T-CELL RECEPTOR; MOLECULAR-COMPONENTS; ANTIBODY; DEGRADATION; IGM AB THE transmembrane domain of the alpha-chain of the T-cell receptor is responsible both for its assembly with the CD3 delta-chain 1 and for rapid degradation of the unassembled chain within the endoplasmic reticulum 2, 3. The determinant for both assembly and degradation is located in a segment of eight residues containing two basic amino acids (Fig. 1). We show here that placement of a single basic residue in the transmembrane domain of the Tac antigen can induce interaction with the CD3 chain, through its transmembrane acidic residue. This interaction is most favoured when the interacting residues are located at the same level in the membrane. The ability to induce protein-protein interaction by placing charge pairs within transmembrane domains suggests an approach to producing artificial dimers. RP COSSON, P (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 16 TC 219 Z9 219 U1 1 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 30 PY 1991 VL 351 IS 6325 BP 414 EP 416 DI 10.1038/351414a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FN856 UT WOS:A1991FN85600061 PM 1827877 ER PT J AU MOZZARELLI, A RIVETTI, C ROSSI, GL HENRY, ER EATON, WA AF MOZZARELLI, A RIVETTI, C ROSSI, GL HENRY, ER EATON, WA TI CRYSTALS OF HEMOGLOBIN WITH THE T-QUARTERNARY STRUCTURE BIND OXYGEN NONCOOPERATIVELY WITH NO BOHR EFFECT SO NATURE LA English DT Article ID HUMAN-HEMOGLOBIN; SINGLE-CRYSTALS; STEREOCHEMISTRY; MECHANISMS; CONSTANTS; AFFINITY; ENZYME; STATE AB THE relationship between the structure and function of haemoglobin has mainly been studied by comparing its X-ray crystal structures with its function in solutions 1-11. To make a direct comparison we have studied the functional properties of haemoglobin in single crystals, an approach that has been an important part of the investigation of several enzyme mechanisms 12, 13. Here we report on the oxygen binding by single crystals of human haemoglobin grown in solutions of polyethylene glycol. Unlike haemoglobin crystals formed in concentrated salt solution, which crack and become disordered on oxygenation 14-16, crystals grown in polyethylene glycol remain intact. X-ray studies have shown that the T (deoxy) quaternary structure of haemoglobin in this crystal at pH 7.0 is maintained at atmospheric oxygen pressure, and that the salt-bridges are not broken 17-19. We find striking differences between oxygen binding by haemoglobin in this crystal and by haemoglobin in solution. Not only is oxygenation of the crystal noncooperative, but the oxygen affinity is independent of pH in the range 6.0-8.5, and is much lower than that of the T state in solution. The lack of cooperativity without a change in quaternary structure is predicted by the two-state allosteric model of Monod, Wyman and Changeux 1, 5. The absence of a Bohr effect without breakage of salt-bridges is predicted by Perutz's stereochemical mechanism 2, 4, 9-11. In contrast to the X-ray result that oxygen binds only to the alpha-haems, our measurements show that the alpha-haems have only a slightly higher affinity than the beta-haems. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RP MOZZARELLI, A (reprint author), UNIV PARMA,INST BIOCHEM SCI,I-43100 PARMA,ITALY. RI Henry, Eric/J-3414-2013; Mozzarelli, Andrea/C-3615-2014 OI Henry, Eric/0000-0002-5648-8696; Mozzarelli, Andrea/0000-0003-3762-0062 NR 35 TC 98 Z9 98 U1 0 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 30 PY 1991 VL 351 IS 6325 BP 416 EP 419 DI 10.1038/351416a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FN856 UT WOS:A1991FN85600062 PM 2034292 ER PT J AU PASSAMANI, E AF PASSAMANI, E TI CLINICAL-TRIALS - ARE THEY ETHICAL SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MYOCARDIAL-INFARCTION RP PASSAMANI, E (reprint author), NHLBI, BETHESDA, MD 20892 USA. NR 14 TC 107 Z9 107 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 30 PY 1991 VL 324 IS 22 BP 1589 EP 1592 DI 10.1056/NEJM199105303242209 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA FN051 UT WOS:A1991FN05100009 PM 1709257 ER PT J AU CLIMENT, I SJOBERG, BM HUANG, CY AF CLIMENT, I SJOBERG, BM HUANG, CY TI CARBOXYL-TERMINAL PEPTIDES AS PROBES FOR ESCHERICHIA-COLI RIBONUCLEOTIDE REDUCTASE SUBUNIT INTERACTION - KINETIC-ANALYSIS OF INHIBITION STUDIES SO BIOCHEMISTRY LA English DT Article ID DIPHOSPHATE REDUCTASE; SYNTHETIC PEPTIDES; DNA-SEQUENCE; VIRUS; GENE; IDENTIFICATION; PROTEIN; MECHANISM AB The active complex of Escherichia coli ribonucleotide reductase comprises two dissociable, nonidentical homodimeric proteins, B1 and B2. When B2 is the varied component, the reductase activity is competitively inhibited by synthetic peptides of varying lengths corresponding to the C-terminus of protein B2. This finding provides the first evidence that the C-terminal peptides and protein B2 share the same binding domain on protein B1. Our data also show that two molecules of peptide can bind to protein B1 with equal affinity. Similar inhibition constants (18-mu-M) were obtained for peptides containing the C-terminal 20, 30, and 37 residues. When the invariant residue Tyr 356 was omitted, a 2-fold decrease in peptide inhibitory ability was observed. A small peptide, lacking the last 11 residues, had virtually no inhibitory potency. These results, coupled with our previous observations that truncated protein B2, in which one or both polypeptide chains are missing approximately 24 C-terminal residues, had considerably lower or no affinity for B1, suggest that the C-terminal regions are the major determinants in the B1-B2 interaction. In the Appendix, two methods for treatment of kinetic situations pertinent to the ribonucleotide reductase system are presented. One method deals with the determination of kinetic parameters for two components present at comparable levels; the other is concerned with the differentiation of linear and nonlinear competitive inhibition involving the binding of two inhibitor molecules. Both methods should find application to other similar cases. C1 UNIV STOCKHOLM,DEPT MOLEC BIOL,S-10691 STOCKHOLM,SWEDEN. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 38 TC 105 Z9 108 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 28 PY 1991 VL 30 IS 21 BP 5164 EP 5171 DI 10.1021/bi00235a008 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FN552 UT WOS:A1991FN55200008 PM 2036382 ER PT J AU CHEN, RF KNUTSON, JR ZIFFER, H PORTER, D AF CHEN, RF KNUTSON, JR ZIFFER, H PORTER, D TI FLUORESCENCE OF TRYPTOPHAN DIPEPTIDES - CORRELATIONS WITH THE ROTAMER MODEL SO BIOCHEMISTRY LA English DT Article ID TIME-RESOLVED FLUORESCENCE; HYDROGEN-DEUTERIUM EXCHANGE; AQUEOUS TRYPTOPHAN; DECAY KINETICS; PEPTIDES; PROTEINS; INDOLE; RESIDUES; DERIVATIVES; MECHANISM AB The multiexponential decay of tryptophan derivatives has previously been explained by the presence of rotamers having different fluorescence lifetimes, but it has been difficult to correlate rotamer structure and physical properties. New time-resolved and static data on dipeptides of the type Trp-X and X-Trp, where X is another aminoacyl residue, are consistent with the rotamer model and allow some correlations. That a dominant rotamer of Trp-X zwitterion has the -NH3+ group near the indole ring was inferred from absorption and fluorescence spectra, titrimetric determination of pK(a) values, photochemical hydrogen-deuterium-exchange experiments, decay-associated spectra, quantum yields, and decay kinetics. Analysis of the lifetime and quantum yield data for Trp dipeptides, especially X-Trp, suggests that static self-quenching is not uncommon. Highly quenched and weak components of the fluorescence do not contribute to the calculated mean lifetime, thus resulting in apparent static quenching. We propose the term quasi-static self-quenching (QSSQ) to distinguish this phenomenon from quenching due to ground-state formation of a dark complex. Mechanisms of quenching and the structure of statically quenched rotamers are discussed. The occurrence of QSSQ supports the idea that rotamers interconvert slowly. A major perceived deficiency of the rotamer model, namely, the apparent inability to predict reasonable rotamer populations from fluorescence decay data, may result from the presence of statically quenched species, which do not contribute to the fluorescence. C1 NIDDKD, CHEM PHYS LAB, BETHESDA, MD 20892 USA. RP NHLBI, CELLULAR BIOL LAB, BETHESDA, MD 20892 USA. NR 58 TC 116 Z9 116 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 28 PY 1991 VL 30 IS 21 BP 5184 EP 5195 DI 10.1021/bi00235a011 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FN552 UT WOS:A1991FN55200011 PM 2036384 ER PT J AU THEVENIN, C KIM, SJ KEHRL, JH AF THEVENIN, C KIM, SJ KEHRL, JH TI INHIBITION OF PROTEIN PHOSPHATASES BY OKADAIC ACID INDUCES AP1 IN HUMAN T-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID GENE-EXPRESSION; TUMOR PROMOTER; JUN PROTEINS; FOS; ONCOGENE; PRODUCT; PHOSPHORYLATION; ACTIVATION; ENCODES; MEMBER AB To examine the role of protein phosphatases in T cell activation,Jurkat cells were treated with okadaic acid, an inhibitor of type 1 and 2A phosphatases, and nuclear extracts were examined for the presence of AP1 as a measure of early T cell activation. Okadaic acid was found to be a potent inducer of AP1. In contrast to phorbol esters such as phorbol myristate acetate (PMA), the induction of AP1 by okadaic acid occurs predominantly by transcriptional activation of the jun and fos family of proto-oncogenes. Surprisingly, while the addition of phytohemagglutinin further enhanced the induction of AP1, the addition of PMA inhibited it. Okadaic acid treatment was found to dramatically increase mRNA transcripts of the jun family of proto-oncogenes including c-jun, junD, and junB and to a lesser extent the fos family including c-fos and fra-1. By comparison, PMA is a very inefficient inducer of the jun gene family in Jurkat cells. Similar to its effect on the induction of AP1 by okadaic acid, PMA inhibits the induction of c-jun mRNA by okadaic acid. Transfection of c-jun promoter constructs confirmed the marked difference between PMA and okadaic acid in inducing c-jun transcription. The induction of AP1 by okadaic acid suggests that protein phosphatases 1 and 2A (PP1 and PP2A) may be involved in T cell activation as important negative regulators of the transcription factor AP1. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,RM 11B-13,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 27 TC 110 Z9 111 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1991 VL 266 IS 15 BP 9363 EP 9366 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM459 UT WOS:A1991FM45900007 PM 1851743 ER PT J AU DUCKWORTH, PF VLAHCEVIC, ZR STUDER, EJ GURLEY, EC HEUMAN, DM BEG, ZH HYLEMON, PB AF DUCKWORTH, PF VLAHCEVIC, ZR STUDER, EJ GURLEY, EC HEUMAN, DM BEG, ZH HYLEMON, PB TI EFFECT OF HYDROPHOBIC BILE-ACIDS ON 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE-ACTIVITY AND MESSENGER-RNA LEVELS IN THE RAT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COENZYME-A REDUCTASE; DENSITY LIPOPROTEIN RECEPTOR; MEVALONATE-DERIVED PRODUCT; STEROL REGULATORY ELEMENT; DEPENDENT PROTEIN-KINASE; ENZYMIC ACTIVITY; TRANSCRIPTIONAL REGULATION; LIVER; CHOLESTEROL; MODULATION AB We have previously reported that relatively hydrophobic bile acids, decreased hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase (reductase) activity whereas, hydrophilic bile acids had little effect on the enzyme. The purpose of the present study was to determine in more detail the mechanism of down-regulation of hepatic reductase activity by hydrophobic bile salts. Groups of rats were fed bile acids of differing hydrophobicity: ursodeoxycholic, cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), or cholesterol for 14 days. Reductase specific activities and concentrations of reductase protein were determined in hepatic microsomes. Quantitation of "steady state" levels of reductase mRNA was performed using Northern and dot blot hybridization. Reductase gene transcriptional activity (nuclear "run-on") was determined in nuclei isolated from livers of animals fed different bile acids. Hydrophobic bile acids and cholesterol significantly decreased reductase activity: CA (57%), CDCA (77%), DCA (73%), cholesterol (89%), and reductase protein levels as measured by an enzyme-linked immunosorbent assay method were also decreased; CA (27%), CDCA (31%), DCA (42%), and cholesterol (35%). Reductase mRNA levels were also decreased after feeding hydrophobic bile acid: CA (43%), CDCA (47%), DCA (54%), and cholesterol (53%). Ursodeoxycholic, a hydrophilic bile acid, caused a much smaller decrease in reductase activity (18%), protein mass (16%), and mRNA levels (10%). Decreased transcriptional activities were observed in CA- and cholesterol-fed rats. Surprisingly, CDCA- and DCA-fed animals showed transcriptional activities similar to control animals even though steady state mRNA levels were low in CDCA- and DCA-fed animals. We hypothesize a post-transcriptional regulation of reductase mRNA by hydrophobic bile acids. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MICROBIOL & IMMUNOL,BOX 678 MCV STN,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,RICHMOND,VA 23298. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. FU NIDDK NIH HHS [P01 DK38030] NR 42 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1991 VL 266 IS 15 BP 9413 EP 9418 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM459 UT WOS:A1991FM45900015 PM 2033042 ER PT J AU BIRCHENALLROBERTS, MC FALK, LA KASPER, J KELLER, J FALTYNEK, CR RUSCETTI, FW AF BIRCHENALLROBERTS, MC FALK, LA KASPER, J KELLER, J FALTYNEK, CR RUSCETTI, FW TI DIFFERENTIAL EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETA-1 (TGF-BETA-1) RECEPTORS IN MURINE MYELOID CELL-LINES TRANSFORMED WITH ONCOGENES - CORRELATION WITH DIFFERENTIAL GROWTH-INHIBITION BY TGF-BETA-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; FACTOR-BETA; MONOCYTIC DIFFERENTIATION; MEMBRANE-RECEPTOR; PROLIFERATION; MODULATION; BINDING AB Transforming growth factor-beta-1 (TGF-beta-1) is a pleiotropic polypeptide hormone known to play an important role as a modulator of hematopoietic processes in human and murine cells. One of the characteristics of TGF-beta-1 is the ability to inhibit the growth of several cell types, including cells of the myeloid lineage. To study the mechanism by which TGF-beta-1 inhibits the growth of myeloid cells, we have used three murine myeloid cell lines, the parental interleukin-3-dependent 32D-123 cell line and two retrovirally infected interleukin-3-independent cell lines (32D-abl, 32D-src), all of which are growth inhibited by TGF-beta-1. Each of these oncogene-transfected cells expresses a greater number of TGF-beta-1 receptors than the parental cell line and responds to TGF-beta-1 with increased sensitivity; 32D and 32D-src cells are 2- and 58-fold more sensitive to TGF-beta-1 inhibition than the parental cell line (ED50 = 35 pM). Both 32D-abl- and 32D-src-transformed cell lines expressed higher levels of the 65- and 85-kDa TGF-beta-1 receptor species than did the parental cells. We observed a correlation between the greater sensitivity of 32D-src cells to TGF-beta-1 and the more rapid down-modulation and reappearance of cell surface TGF-beta-1 receptors on 32D-src cells. Thus, the level of TGF-beta-1 receptor expression and rate of reexpression both have a crucial regulatory effect on the functional activity of the TGF-beta-1 ligand. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. STERLING DRUG INC,STERLING RES GRP,MALVERN,PA 19355. RP BIRCHENALLROBERTS, MC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS DEV PROGRAM,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 39 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1991 VL 266 IS 15 BP 9617 EP 9621 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM459 UT WOS:A1991FM45900045 PM 1851752 ER PT J AU NAKAJIMA, M DECHAVIGNY, A JOHNSON, CE HAMADA, J STEIN, CA NICOLSON, GL AF NAKAJIMA, M DECHAVIGNY, A JOHNSON, CE HAMADA, J STEIN, CA NICOLSON, GL TI SURAMIN - A POTENT INHIBITOR OF MELANOMA HEPARANASE AND INVASION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR RECEPTOR-BINDING; COLON-CARCINOMA-CELLS; EXTRACELLULAR-MATRIX; GROWTH-FACTOR; REVERSE-TRANSCRIPTASE; SULFATE DEGRADATION; BASEMENT-MEMBRANE; RAT; MUCOPOLYSACCHARIDOSIS; METASTASIS AB Suramin, a polysulfonated naphthylurea, has anti-reverse transcriptase and anti-proliferative activities and inhibits the binding of various growth factors to their cell surface receptors. This drug is used in the treatment of acquired immunodeficiency syndrome and several types of cancers. Increased levels of circulating glycosaminoglycans have been observed in suramin-treated cancer patients, suggesting that it may inhibit glycosaminoglycan catabolism. Melanoma-derived heparanase, a heparan sulfate-specific endo-beta-D-glucuronidase that plays an important role in metastatic melanoma cell invasion through basement membranes, is inhibited by suramin in a dose-dependent manner: 100% inhibition was observed at a concentration of approximately 100-mu-M. Structurally related polysulfonated compounds, such as trypan blue and Evans blue, had lower heparanase inhibitory activities: the concentrations required for 50% heparanase inhibition (ID50) were 310-320-mu-M and six times higher than for suramin (ID50 = 46-mu-M). Oversulfated heparin tetrasaccharide, whose average molecular size is similar to suramin, had also much lower heparanase inhibitory activity than suramin. The inhibition constants (K(i)) for suramin and oversulfated heparin tetrasaccharide were 48 and 290-mu-M, respectively. Suramin had a remarkable inhibitory activity against B16 melanoma cell invasion through reconstituted basement membranes (ID50 < 10-mu-M). The inhibitory effects of suramin on melanoma heparanase and cell invasion appeared to be completely independent of its antiproliferative activity, because significant effects on melanoma cell growth were not observed at the concentrations of suramin used in this study. The results suggest that the antimetastatic effects of suramin may be due to its antiinvasive rather than antiproliferative activities. C1 NCI,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. RP NAKAJIMA, M (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT TUMOR BIOL,BOX 108,HOUSTON,TX 77030, USA. RI Hamada, Jun-ichi/D-7452-2012 FU NCI NIH HHS [R01-CA41524, R35-CA44352] NR 39 TC 152 Z9 152 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1991 VL 266 IS 15 BP 9661 EP 9666 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM459 UT WOS:A1991FM45900051 PM 2033058 ER PT J AU ROSENWALD, AG PAGANO, RE RAVIV, Y AF ROSENWALD, AG PAGANO, RE RAVIV, Y TI ACTIVATION OF 5-[I-125] IODONAPHTHYL-1-AZIDE VIA EXCITATION OF FLUORESCENT (N-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)) LIPID ANALOGS IN LIVING CELLS - A POTENTIAL TOOL FOR IDENTIFICATION OF COMPARTMENT-SPECIFIC PROTEINS AND PROTEINS INVOLVED IN INTRACELLULAR-TRANSPORT AND METABOLISM OF LIPIDS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-ERYTHROCYTE MEMBRANE; CULTURED FIBROBLASTS; PLASMA-MEMBRANE; GOLGI-APPARATUS; BINDING PROTEINS; CERAMIDE ANALOG; ANIMAL-CELLS; SPHINGOMYELIN; BIOSYNTHESIS; PHOSPHATIDYLCHOLINE AB We describe a new technique for analysis of proteins located near fluorescent lipid analogs in intact living cells using the membrane-permeant, photoactivatable probe, 5-[I-125]iodonaphthyl-1-azide ([I-125]INA). [I-125]INA can be activated directly with UV light or indirectly through excitation of adjacent fluorophores (photosensitizers) with visible light to modify nearby proteins covalently with I-125. In this report we demonstrate that fluorescent phospholipids and sphingolipids containing N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-6-aminocaproic acid serve as appropriate photosensitizers for [I-125]INA. Using Chinese hamster ovary fibroblasts, we optimized the labeling conditions with respect to lipid concentration and time of irradiation and then examined the profiles of cellular proteins that were labeled when fluorescent analogs of ceramide, sphingomyelin, and phosphatidic acid were used as photosensitizers in living cells. The use of different fluorescent lipids, which label different subcellular compartments of cells as determined by fluorescence microscopy, derivatized different sets of cellular proteins with I-125. The labeled proteins were subsets of the total set of proteins available for derivatization as determined by direct activation of [I-125]INA. Most proteins labeled by this procedure were pelleted by centrifugation of cell lysates at high speed (260,000 x g), but several soluble proteins were also labeled under these conditions. The implications of using this technique for identification of compartment-specific proteins and proteins involved in lipid metabolism and transport are discussed. C1 CARNEGIE INST WASHINGTON,DEPT EMBRYOL,115 W UNIV PKWY,BALTIMORE,MD 21210. NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [R37 GM22942] NR 41 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1991 VL 266 IS 15 BP 9814 EP 9821 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM459 UT WOS:A1991FM45900072 PM 2033068 ER PT J AU MACKAY, K DANIELPOUR, D AF MACKAY, K DANIELPOUR, D TI NOVEL 150-KDA AND 180-KDA GLYCOPROTEINS THAT BIND TRANSFORMING GROWTH-FACTOR (TGF)-BETA-1 BUT NOT TGF-BETA-2 ARE PRESENT IN SEVERAL CELL-LINES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-BETA; GLYCOSAMINOGLYCAN CHAINS; MEMBRANE-RECEPTOR; LIGAND-BINDING; PROTEINS; PROTEOGLYCAN; FIBROBLASTS; EXPRESSION; CULTURE AB We identified transforming growth factor-beta (TGF-beta)-binding proteins which are distinct from previously described TGF-beta receptors or TGF-beta-binding proteins. These TGF-beta-binding proteins migrate as 150- and 180-kDa I-125-TGF-beta-1 affinity-labeled complexes which are consistently co-expressed in A549, Mv 1Lu, MG-63, and BS-C-1 cells. They differ from the types I, II, and III TGF-beta-receptors in their electrophoretic mobilities, their lack of binding to TGF-beta-2, and their failure to undergo the marked down-regulation seen with types I,II, and III receptors following a 16-h incubation with TGF-beta-1. The 150- and 180-kDa TGF-beta-binding proteins also are distinct from the recently described disulfide-linked TGF-beta-1-binding proteins which are present in rat glomeruli. In contrast to the glomerular TGF-beta-1-binding proteins the electrophoretic mobilities of the 150- and 180-kDa binding proteins are unchanged following reduction. In addition, the 150- and 180-kDa TGF-beta-binding proteins are present in the detergent-rich phase during Triton X-114 phase separation, whereas the glomerular TGF-beta-binding proteins partition exclusively into the detergent-poor phase. C1 NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. RP MACKAY, K (reprint author), NIDDKD, METAB DIS BRANCH,KIDNEY DIS SECT,BLDG 10,RM 3N106, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 25 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1991 VL 266 IS 15 BP 9907 EP 9911 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM459 UT WOS:A1991FM45900084 PM 1851759 ER PT J AU TULLY, JG BASEMAN, JB AF TULLY, JG BASEMAN, JB TI MYCOPLASMA SO LANCET LA English DT Letter ID GENITALIUM; PNEUMONIAE; PROTEIN; TRACT C1 UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,SAN ANTONIO,TX 78284. RP TULLY, JG (reprint author), NIAID,FREDERICK CANC RES DEV CTR,MYCOPLASMA SECT,FREDERICK,MD 21701, USA. NR 10 TC 20 Z9 20 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 25 PY 1991 VL 337 IS 8752 BP 1296 EP 1296 DI 10.1016/0140-6736(91)92971-4 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FN047 UT WOS:A1991FN04700056 PM 1674098 ER PT J AU CRAIGIE, R MIZUUCHI, K BUSHMAN, FD ENGELMAN, A AF CRAIGIE, R MIZUUCHI, K BUSHMAN, FD ENGELMAN, A TI A RAPID INVITRO ASSAY FOR HIV DNA INTEGRATION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRUS INTEGRATION; VIRAL-DNA; PROTEIN; RECOMBINATION; SEQUENCES AB Retroviruses synthesize a double stranded DNA copy of their RNA genome after infection of a permissive cell and subsequent integration of this DNA copy into the host genome is necessary for normal viral replication. Integration occurs by a specialized DNA recombination reaction, mediated by the viral IN protein. Because this reaction has no known cellular counterpart, it is a particularly attractive target in the search for specific inhibitors with low toxicity that may serve as therapeutic antiviral agents. We present a simple assay system that is suitable for screening potential inhibitors of HIV DNA integration. Only short oligonucleotides matching one end of HIV DNA and purified HIV IN protein are required as substrates. Furthermore, since each step of the assay can be carried out in the wells of microtiter plates, large numbers of reactions can be processed simultaneously. RP CRAIGIE, R (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 16 TC 94 Z9 100 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 MAY 25 PY 1991 VL 19 IS 10 BP 2729 EP 2734 DI 10.1093/nar/19.10.2729 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900024 PM 2041748 ER PT J AU LATIF, F GLENN, GM RAYFORD, W WEI, M GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM RAYFORD, W WEI, M GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB41-10(D3S618) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI, FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK, BLDG 560,ROOM 12-71, FREDERICK, MD 21701 USA. FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, FREDERICK, MD 21701 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2797 EP 2797 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900051 ER PT J AU LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB25-55(D3S602) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI, FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK, BLDG 560,ROOM 12-71, FREDERICK, MD 21701 USA. FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, FREDERICK, MD 21701 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2797 EP 2797 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900050 ER PT J AU LATIF, F GLENN, GM RAYFORD, W GEIL, L YAO, M DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM RAYFORD, W GEIL, L YAO, M DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB30-62'(D3S606) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI, FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK, BLDG 560,ROOM 12-71, FREDERICK, MD 21701 USA. FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, FREDERICK, MD 21701 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2798 EP 2798 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900053 ER PT J AU LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB46-95(D3S620) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI, FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK, BLDG 560,ROOM 12-71, FREDERICK, MD 21701 USA. FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, FREDERICK, MD 21701 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2798 EP 2798 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900052 ER PT J AU LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB46-35'(D3S636) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI, FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK, BLDG 560,ROOM 12-71, FREDERICK, MD 21701 USA. FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, FREDERICK, MD 21701 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2799 EP 2799 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900055 ER PT J AU LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB17-58(D3S598) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI, FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK, BLDG 560,ROOM 12-71, FREDERICK, MD 21701 USA. FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, FREDERICK, MD 21701 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2799 EP 2799 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900054 ER PT J AU DELISIO, J LATIF, F GLENN, GM GEIL, L YAO, M HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF DELISIO, J LATIF, F GLENN, GM GEIL, L YAO, M HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB28-62(D3S736) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,FREDERICK,MD 21701. NR 2 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2800 EP 2800 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900056 PM 1710349 ER PT J AU LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB29-48(D3S624) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,FREDERICK,MD 21701. NR 2 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2800 EP 2800 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900057 PM 1710350 ER PT J AU LATIF, F GLENN, GM RAYFORD, W GEIL, L YAO, M DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM RAYFORD, W GEIL, L YAO, M DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB35-53(D3S731) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI, FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK, BLDG 560,ROOM 12-71, FREDERICK, MD 21701 USA. FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, FREDERICK, MD 21701 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2801 EP 2801 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900059 ER PT J AU LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM RAYFORD, W GEIL, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB11-95(D3S730) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI, FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK, BLDG 560,ROOM 12-71, FREDERICK, MD 21701 USA. FREDERICK CANC RES FACIL, PROGRAM RESOURCES INC, FREDERICK, MD 21701 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2801 EP 2801 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900058 ER PT J AU LATIF, F GLENN, GM GEIL, L SCHMIDT, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI AF LATIF, F GLENN, GM GEIL, L SCHMIDT, L DELISIO, J HAMPSCH, K ORCUTT, ML ZBAR, B LERMAN, MI TI A NEW POLYMORPHIC PROBE ON CHROMOSOME 3P-LAMBDA-LIB4A-52''(D3S732) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,FREDERICK CANC RES FACIL,IMMUNOL LAB,FT DETRICK,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 25 PY 1991 VL 19 IS 10 BP 2802 EP 2802 DI 10.1093/nar/19.10.2802 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900060 PM 1674995 ER PT J AU POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR AF POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN FMS-RELATED TYROSINE KINASE GENE (FLT1) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,ROOM 131,WASHINGTON,DC 20032, USA. NR 3 TC 14 Z9 14 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 MAY 25 PY 1991 VL 19 IS 10 BP 2803 EP 2803 DI 10.1093/nar/19.10.2803-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FP319 UT WOS:A1991FP31900063 PM 2041764 ER PT J AU VERICAT, JA CHENG, SC DIPPLE, A AF VERICAT, JA CHENG, SC DIPPLE, A TI ABSOLUTE-CONFIGURATION OF 7,12-DIMETHYLBENZ[A]ANTHRACENE-DNA ADDUCTS IN MOUSE EPIDERMIS SO CANCER LETTERS LA English DT Article DE P-32-POSTLABELING; 7,12-DIMETHYLBENZ[A]ANTHRACENE; DNA ADDUCTS; MOUSE EPIDERMIS; STEREOCHEMISTRY ID EMBRYO CELL-CULTURES; DNA ADDUCTS; 7,12-DIMETHYLBENZ(A)ANTHRACENE; BINDING; SKIN; EPOXIDE; INVITRO; INVIVO AB P-32-Postlabeling was used to monitor the formation of DMBA-DNA adducts in mouse epidermis from each enantiomer of the trans 3,4-dihydrodiol. It was shown that the (4R,3R)-dihydrodiol is converted to the anti (4R,3S)-dihydrodiol (2S,1R)-epoxide which reacts with deoxyguanosine and deoxyadenosine residues in epidermal DNA to yield two of the major adducts formed when DMBA itself binds to epidermal DNA. The third major DMBA-derived adduct with deoxyadenosine residues was shown to arise from the (4S,3R)-dihydrodiol through the intermediacy of the syn (4S,3R)-dihydrodiol (2S,1R)-epoxide. C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 19 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 24 PY 1991 VL 57 IS 3 BP 237 EP 242 DI 10.1016/0304-3835(91)90163-C PG 6 WC Oncology SC Oncology GA FP403 UT WOS:A1991FP40300009 PM 1903326 ER PT J AU LABROO, RB LABROO, VM KING, MM COHEN, LA AF LABROO, RB LABROO, VM KING, MM COHEN, LA TI AN IMPROVED SYNTHESIS OF DIOXINDOLE-3-PROPIONIC ACID AND SOME TRANSFORMATIONS OF THE C-3 HYDROXYL GROUP SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID AMINO-ACIDS; L-ALANINE; TRYPTOPHANASE; ESTERS; CARBOCATIONS; CYCLIZATION; INDOLE AB Dioxindole-3-propionic acid lactone (3) is obtained in 80% yield by oxidative cyclization of indole-3-propionic acid with t-BuBr/DMSO. In the presence of 18-crown-6 in DMSO, KCN opens the spirolactone ring of 3 at C-3 with the formation of 3-cyanooxindole-3-propionic acid (4a) in 14% yield. Methanolysis of the lactone is strongly promoted by DMAP, and the resulting 3-hydroxy ester (5) is converted into the 3-fluoro ester (6) with methyl DAST. Every attempt to isolate 3-fluorooxindole-3-propionic acid resulted in rapid intramolecular displacement of fluorine by the free carboxyl group to reform the spirolactone. The 3-hydroxy ester is converted into the 3-chloro ester (9) with SOCl2/Et3N. The halogen is readily displaced by nucleophiles (e.g., N3-, CN-, NH3, AcO-, H2O) to generate the corresponding methyl 3-X-oxindole-3-propionate. Saponification of the ester function provides the corresponding 3-X-oxindole-3-propionic acid. Acetylation of the 3-hydroxy ester provides a separable mixture of the O-acetyl (16) and N-acetyl (17) derivatives. As in the case of 3, the O-acetyl derivative undergoes hydrogenolysis at C-3, while the 3-hydroxyl function is stable to removal by hydrogenolysis. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT CHEM,WASHINGTON,DC 20052. NR 41 TC 27 Z9 27 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD MAY 24 PY 1991 VL 56 IS 11 BP 3637 EP 3642 DI 10.1021/jo00011a035 PG 6 WC Chemistry, Organic SC Chemistry GA FN573 UT WOS:A1991FN57300035 ER PT J AU PIATIGORSKY, J WISTOW, G AF PIATIGORSKY, J WISTOW, G TI THE RECRUITMENT OF CRYSTALLINS - NEW FUNCTIONS PRECEDE GENE DUPLICATION SO SCIENCE LA English DT Editorial Material ID ALPHA-B-CRYSTALLIN; LENS CRYSTALLINS; TRANSGENIC MICE; ALDEHYDE DEHYDROGENASE; ENZYME-CRYSTALLINS; STRUCTURAL PROTEIN; DELTA-CRYSTALLIN; DUCK LENS; EYE LENS; EXPRESSION RP PIATIGORSKY, J (reprint author), NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 39 TC 251 Z9 252 U1 1 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 MAY 24 PY 1991 VL 252 IS 5009 BP 1078 EP 1079 DI 10.1126/science.252.5009.1078 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FN056 UT WOS:A1991FN05600031 PM 2031181 ER PT J AU KAMEN, MD AF KAMEN, MD TI INTERNATIONAL WORKSHOP ON NONMITOCHONDRIAL CYTOCHROMES-C - A SHORT FOREWORD WITH SOME HISTORY SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE CYTOCHROME-C; HEME PROTEIN; PROTEIN SEQUENCE AB A brief description of die informal workshop on non-mitochondrial cytochromes c is given. The organization of the meeting, the personnel participating and the scope of research effort are discussed. A brief historical account is included to place the Symposium reports in context. RP KAMEN, MD (reprint author), NIH,FOGARTY SCHOLAR RESIDENCE PROGRAM,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 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 MAY 23 PY 1991 VL 1058 IS 1 BP 3 EP 4 DI 10.1016/S0005-2728(05)80255-5 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FT345 UT WOS:A1991FT34500002 PM 1646013 ER PT J AU BARTON, NW BRADY, RO DAMBROSIA, JM DIBISCEGLIE, AM DOPPELT, SH HILL, SC MANKIN, HJ MURRAY, GJ PARKER, RI ARGOFF, CE GREWAL, RP YU, KT AF BARTON, NW BRADY, RO DAMBROSIA, JM DIBISCEGLIE, AM DOPPELT, SH HILL, SC MANKIN, HJ MURRAY, GJ PARKER, RI ARGOFF, CE GREWAL, RP YU, KT TI REPLACEMENT THERAPY FOR INHERITED ENZYME DEFICIENCY - MACROPHAGE-TARGETED GLUCOCEREBROSIDASE FOR GAUCHERS-DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CELLS; GENE AB Background and Methods. Gaucher's disease, the most prevalent of the sphingolipid storage disorders, is caused by a deficiency of the enzyme glucocerebrosidase (glucosylceramidase). Enzyme replacement was proposed as a therapeutic strategy for this disorder in 1966. To assess the clinical effectiveness of this approach, we infused macrophage-targeted human placental glucocerebrosidase (60 IU per kilogram of body weight every 2 weeks for 9 to 12 months) into 12 patients with type 1 Gaucher's disease who had intact spleens. The frequency of infusions was increased to once a week in two patients (children) during part of the trial because they had clinically aggressive disease. Results. The hemoglobin concentration increased in all 12 patients, and the platelet count in 7. Serum acid phosphatase activity decreased in 10 patients during the trial, and the plasma glucocerebroside level in 9. Splenic volume decreased in all patients after six months of treatment, and hepatic volume in five. Early signs of skeletal improvements were seen in three patients. The enzyme infusions were well tolerated, and no antibody to the exogenous enzyme developed. Conclusions. Intravenous administration of macrophage-targeted glucocerebrosidase produces objective clinical improvement in patients with type 1 Gaucher's disease. The hematologic and visceral responses to enzyme replacement develop more rapidly than the skeletal response. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,BETHESDA,MD. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. RP BARTON, NW (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,BLDG 10,RM 3D04,BETHESDA,MD 20892, USA. OI Kaneski, Christine/0000-0003-1453-2502 NR 30 TC 851 Z9 873 U1 2 U2 31 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 23 PY 1991 VL 324 IS 21 BP 1464 EP 1470 DI 10.1056/NEJM199105233242104 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA FM460 UT WOS:A1991FM46000004 PM 2023606 ER PT J AU HIGGINS, M AF HIGGINS, M TI RISK-FACTORS ASSOCIATED WITH CHRONIC OBSTRUCTIVE LUNG-DISEASE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID MORTALITY; TECUMSEH; DEFICIENCY; INDEX RP HIGGINS, M (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 22 TC 42 Z9 45 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 MAY 22 PY 1991 VL 624 BP 7 EP 17 DI 10.1111/j.1749-6632.1991.tb17001.x PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ454 UT WOS:A1991FZ45400002 PM 2064251 ER PT J AU SMITH, SS GORELICK, DA OHARA, BF UHL, GR AF SMITH, SS GORELICK, DA OHARA, BF UHL, GR TI THE DOPAMINE D2 RECEPTOR GENE AND ALCOHOLISM SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID ASSOCIATION RP SMITH, SS (reprint author), NIDA,BALTIMORE,MD, USA. NR 5 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1991 VL 265 IS 20 BP 2667 EP 2668 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FL989 UT WOS:A1991FL98900014 ER PT J AU GOLDMAN, D BROWN, GL BOLOS, AM LUCASDERSE, S DEAN, M AF GOLDMAN, D BROWN, GL BOLOS, AM LUCASDERSE, S DEAN, M TI THE DOPAMINE D2 RECEPTOR GENE AND ALCOHOLISM - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID ASSOCIATION C1 PROGRAM RESOURCES INC,FREDERICK,MD. RP GOLDMAN, D (reprint author), NIAAA,BETHESDA,MD, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 4 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 22 PY 1991 VL 265 IS 20 BP 2668 EP 2668 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FL989 UT WOS:A1991FL98900015 ER PT J AU CLORE, GM OMICHINSKI, JG GRONENBORN, AM AF CLORE, GM OMICHINSKI, JG GRONENBORN, AM TI SLOW CONFORMATIONAL DYNAMICS AT THE METAL COORDINATION SITE OF A ZINC FINGER SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID SPECTROSCOPY; EXCHANGE RP CLORE, GM (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 11 TC 13 Z9 13 U1 0 U2 0 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 MAY 22 PY 1991 VL 113 IS 11 BP 4350 EP 4351 DI 10.1021/ja00011a059 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA FN005 UT WOS:A1991FN00500059 ER PT J AU SOBEL, EC COLLETT, TS AF SOBEL, EC COLLETT, TS TI DOES VERTICAL DISPARITY SCALE THE PERCEPTION OF STEREOSCOPIC DEPTH SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article ID DISTANCE; CONSTANCY AB It has been suggested that a measure of the gradients of vertical disparity over a surface may scale the mapping between horizontal disparity and perceived depth. We have investigated this possibility by obtaining estimates of the depth within stereograms that simulated two apposed fronto-parallel planes placed at different distances from an observer. The gradients of vertical disparity in a stereogram were set to simulate those appropriate to a viewing distance of 12.5 cm, 25 cm, 50 cm or 100 cm, whereas the distance specified by vergence and accommodative cues was always fixed at 50 cm. Judgements of the perceived depth between the two planes were uninfluenced by changes in the gradients of vertical disparity. It thus seems that the human visual system does not employ vertical disparity as a scaling parameter in stereoscopic depth judgements. C1 NEI, SENSORIMOTOR RES LAB, BETHESDA, MD 20892 USA. NR 16 TC 31 Z9 31 U1 0 U2 2 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD MAY 22 PY 1991 VL 244 IS 1310 BP 87 EP 90 DI 10.1098/rspb.1991.0055 PG 4 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA FN514 UT WOS:A1991FN51400003 PM 1679553 ER PT J AU TAN, GS KELLY, P KIM, J WARTELL, RM AF TAN, GS KELLY, P KIM, J WARTELL, RM TI COMPARISON OF CAMP RECEPTOR PROTEIN (CRP) AND A CAMP-INDEPENDENT FORM OF CRP BY RAMAN-SPECTROSCOPY AND DNA-BINDING SO BIOCHEMISTRY LA English DT Article ID CATABOLITE ACTIVATOR PROTEIN; ADENOSINE CYCLIC 3',5'-MONOPHOSPHATE; ESCHERICHIA-COLI; GEL-ELECTROPHORESIS; COOPERATIVE BINDING; SECONDARY STRUCTURE; LAC PROMOTER; AMP; GENE; EQUILIBRIUM AB The secondary structures of the cAMP receptor protein (CRP), a complex of CRP and cAMP, and a cAMP-independent receptor protein mutant (CRP*141gln) were examined by using Raman spectroscopy. Spectra were obtained from CRP and CRP*141gln dissolved in 0.3 M NaCl and 30 mM sodium phosphate at protein concentrations of 30-40 mg/mL. CRP and CRP.cAMP1 were compared at lower protein concentrations (10-12 mg/mL) in a solvent of 0.35 M NaCl and 20 mM sodium phosphate. Raman analysis indicates that CRP structural changes induced by one bound cAMP or by the Gly to Gln mutation at residue 141 are small. Spectra of the three CRP samples are essentially identical from 400 to 1900 cm-1. This result differs from the Raman spectroscopy study of CRP and CRP.cAMP2 cocrystals [DeGrazia et al. (1990) Biochemistry 29, 3557]. The latter work showed spectral differences between CRP and CRP.cAMP2 consistent with alterations in the protein conformation. These studies indicate that CRP and CRP.cAMP1 in solution are similar in structure and differ from CRP.cAMP2 cocrystals. Protease digestion and a DNA binding assay were also employed to characterize the wild-type and mutant proteins. CRP*141gln exhibited the same conformational characteristics of previously reported cAMP independent mutant proteins. It was sensitive to proteolytic attack in the absence of cAMP, or upon addition of cGMP. In the absence of cAMP, both wild-type and mutant CRPs bound noncooperatively to a 62 bp lac promoter DNA. The equilibrium constants were almost-equal-to 10(6) M-1 in 0.1 M Na+. CRP*141gln had a 2-4-fold higher affinity for the 62 bp DNA than CRP. Both proteins showed cooperative binding with 75 and 84 bp DNAs lacking crp sites. C1 GEORGIA INST TECHNOL,SCH BIOL,ATLANTA,GA 30332. GEORGIA INST TECHNOL,SCH PHYS,ATLANTA,GA 30332. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 32 TC 29 Z9 29 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 MAY 21 PY 1991 VL 30 IS 20 BP 5076 EP 5080 DI 10.1021/bi00234a034 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM712 UT WOS:A1991FM71200034 PM 1645189 ER PT J AU PROUDFOOT, AEI DAVIES, JG TURCATTI, G WINGFIELD, PT AF PROUDFOOT, AEI DAVIES, JG TURCATTI, G WINGFIELD, PT TI HUMAN INTERLEUKIN-5 EXPRESSED IN ESCHERICHIA-COLI - ASSIGNMENT OF THE DISULFIDE BRIDGES OF THE PURIFIED UNGLYCOSYLATED PROTEIN SO FEBS LETTERS LA English DT Article DE INTERLEUKIN-5; RECOMBINANT DNA TECHNOLOGY; DISULFIDE BOND; PROTEOLYTIC DIGESTION; PEPTIDE MAPPING; HOMODIMERIC SUBUNIT STRUCTURE ID CELL REPLACING FACTOR; GROWTH-FACTOR; RESOLUTION; CLONING; ANALOGS AB Human interleukin-5 is a homodimer; each subunit contains two cysteine residues that form two inter-subunit disulfide bonds. The topology of the disulfides in recombinant human interleukin-5 produced in Escherichia coli was studied by proteolytic digestion and peptide mapping. Disulfide linked peptides containing cysteine 42 linked to cysteine 84 were isolated. This indicated that cysteines 42 and 84 of one subunit were linked in an antiparallel manner to cysteines 84 and 42 of the other subunit. C1 UNIV GENEVA,DEPT BIOCHIM MED,CH-1211 GENEVA 4,SWITZERLAND. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. RP PROUDFOOT, AEI (reprint author), GLAXO INST MOLEC BIOL SA,ROUTE ACACIAS 46,CH-1221 GENEVA 24,SWITZERLAND. NR 17 TC 20 Z9 21 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 20 PY 1991 VL 283 IS 1 BP 61 EP 64 DI 10.1016/0014-5793(91)80553-F PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FP194 UT WOS:A1991FP19400015 PM 2037074 ER PT J AU REINCKE, M WINKELMANN, W ALLOLIO, B AF REINCKE, M WINKELMANN, W ALLOLIO, B TI CORTISOL RESPONSE TO CORTICOTROPIN AND SURVIVAL IN SEPTIC SHOCK SO LANCET LA English DT Letter C1 UNIV COLOGNE,KRANKENHAUS MERHEIM,MED CLIN 2,W-5000 COLOGNE 91,GERMANY. RP REINCKE, M (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 18 PY 1991 VL 337 IS 8751 BP 1230 EP 1231 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FM261 UT WOS:A1991FM26100055 ER PT J AU WU, YN WAGNER, PD AF WU, YN WAGNER, PD TI EFFECTS OF PHOSPHATASE INHIBITORS AND A PROTEIN PHOSPHATASE ON NOREPINEPHRINE SECRETION BY PERMEABILIZED BOVINE CHROMAFFIN CELLS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE CALCIUM; OKADAIC ACID; SECRETION; PROTEIN PHOSPHATASE, TYPE-2A ID STARFISH OOCYTE MATURATION; OKADAIC ACID; CATECHOLAMINE SECRETION; ADRENAL-MEDULLA; INTRACELLULAR MICROINJECTION; DEPENDENT EXOCYTOSIS; TUMOR PROMOTER; SMOOTH-MUSCLE; SPONGE TOXIN; PHOSPHORYLATION AB A protein phosphatase and phosphatase inhibitors were used to examine the role of protein phosphorylation in the regulation of norepinephrine secretion in digitonin-permeabilized bovine chromaffin cells. Addition of okadaic acid, a potent inhibitor of type 1 and type 2A protein phosphatases, or 1-naphthylphosphate, a more general phosphatase inhibitor, to digitonin-permeabilized chromaffin cells caused about a 100% increase in the amount of norepinephrine secreted in the absence of Ca+ (in 5 mM EGTA) without affecting the amount of norepinephrine secreted in the presence of 10-mu-M free Ca 2+. This stimulation of norepinephrine secretion by protein phosphatase inhibitors suggests that in the absence of Ca2+ there is a slow rate phosphorylation and that this phosphorylation triggers secretion. Addition of an exogenous type 2A protein phosphatase caused almost a 50% decrease in Ca2+-dependent norepinephrine secretion. Thus, the amounts of norepinephrine released both in the absence of Ca2+ and in the presence of Ca2+ appear to depend upon the level of protein phosphorylation. C1 NCI,BIOCHEM LAB,BLDG 37,ROOM 4C-24,BETHESDA,MD 20892. NR 34 TC 24 Z9 24 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 MAY 17 PY 1991 VL 1092 IS 3 BP 384 EP 390 DI 10.1016/S0167-4889(97)90016-1 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FR201 UT WOS:A1991FR20100016 PM 1646643 ER PT J AU HIRAMATSU, Y AMBUDKAR, IS BAUM, BJ AF HIRAMATSU, Y AMBUDKAR, IS BAUM, BJ TI CHARACTERIZATION OF HIGH-AFFINITY GTPASE ACTIVITY CORRELATED TO BETA-ADRENERGIC-RECEPTOR STIMULATION OF ADENYLYL CYCLASE IN RAT PAROTID MEMBRANES SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE PAROTID; GTPASE; BETA-ADRENOCEPTOR; ADENYLYL CYCLASE; G-PROTEIN; SIGNAL TRANSDUCTION; CHOLERA TOXIN ID NUCLEOTIDE BINDING-PROTEINS; ALPHA-AMYLASE RELEASE; TURN-OFF REACTION; CHOLERA-TOXIN; GUANINE-NUCLEOTIDES; PERTUSSIS TOXIN; HYDROLYSIS; ADIPOCYTE; AGENTS; CELLS AB Beta-Adrenergic receptor stimulation of adenylyl cyclase involves the activation of a GTP-binding regulatory protein (G-protein, termed here Gs). Inactivation of this G-protein is associated with the hydrolysis of bound GTP by an intrinsic high affinity GTPase activity. In the present study, we have characterized the GTPase activity in a Gs-enriched rat parotid gland membrane fraction. Two GTPase activities were resolved; a high affinity GTPase activity displaying Michaelis-Menten kinetics with increasing concentrations of GTP, and a low affinity GTPase activity which increased linearly with GTP concentrations up to 10 mM. The beta-adrenergic agonist isoproterenol (10-mu-M) increased the V(max) of the high affinity GTPase component approx. 50% from 90 to 140 pmol/mg protein per min, but did not change its K(m) value (almost-equal-to 450 nM). Isoproterenol also stimulated adenylyl cyclase activity in parotid membranes both in the absence or presence of GTP. In the presence of a non-hydrolyzable GTP analogue, guanosine 5'-(3-O-thio)triphosphate (GTP-gamma-S), isoproterenol increased cAMP formation to the same extent as that observed with AlF4-. Cholera toxin treatment of parotid membranes led to the ADP-ribosylation of two proteins (almost-equal-to 45 and 51 kDa). Cholera toxin also specifically decreased the high affinity GTPase activity in membranes and increased cAMP formation induced by GTP in the absence or the presence of isoproterenol. These data demonstrate that the high affinity GTPase characterized here is the 'turn-off' step for the adenylyl cyclase activation seen following beta-adrenergic stimulation of rat parotid glands. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892. NR 35 TC 1 Z9 1 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 MAY 17 PY 1991 VL 1092 IS 3 BP 391 EP 396 DI 10.1016/S0167-4889(97)90017-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FR201 UT WOS:A1991FR20100017 PM 1646644 ER PT J AU ROYCE, LS BAUM, BJ AF ROYCE, LS BAUM, BJ TI PHYSIOLOGICAL LEVELS OF SALIVARY EPIDERMAL GROWTH-FACTOR STIMULATE MIGRATION OF AN ORAL EPITHELIAL-CELL LINE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Note DE EPIDERMAL GROWTH FACTOR; CHEMOTAXIS; SALIVA; (HUMAN ORAL EPITHELIAL CELL LINE) ID SUB-MANDIBULAR GLAND; TISSUE; REGENERATION; ENHANCEMENT; WOUNDS; ALPHA; BETA; RATS; SKIN; EGF AB An established line of human oral epithelial cells exhibits chemotaxis to epidermal growth factor (EGF). The directed migration of these cells is time dependent with an approximate 10-fold increase in the number of cells responding to the chemoattractant by 6 h. Cell migration occurs in a concentration dependent manner with maximal response at approximately 1 ng/ml. This maximal chemotactic response occurs within the physiologic concentration range for EGF found in human saliva. These data suggest that EGF may be important for the maintenance of an intact oral epithelial (mucosal) barrier, and may play a vital role in oral mucosal wound healing. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. RP ROYCE, LS (reprint author), NIDR,DEV BIOL & ANOMALIES LAB,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. NR 29 TC 22 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD MAY 17 PY 1991 VL 1092 IS 3 BP 401 EP 403 DI 10.1016/S0167-4889(97)90019-7 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FR201 UT WOS:A1991FR20100019 PM 2049404 ER PT J AU DURCAN, MJ MORGAN, PF AF DURCAN, MJ MORGAN, PF TI INTRACEREBROVENTRICULAR PERTUSSIS TOXIN ENHANCES SENSITIVITY TO N-METHYL-D-ASPARTATE-INDUCED SEIZURES IN MICE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE PERTUSSIS TOXIN; NMDA (N-METHYL-D-ASPARTATE); SEIZURES; (MOUSE) ID BINDING; GLYCINE; MK-801; BRAIN AB Thc effect of pretreatment with pertussis toxin on N-methyl-D-aspartate (NMDA)-induced seizures was investigated in mice. In animals treated with pertussis toxin (0.5-mu-g/animal i.c.v) five days prior to testing the convulsant ED50 of NMDA was calculated to be 18 mg/kg whereas it was calculated to be 107 mg/kg in sham-treated animals. These results suggest the pertussis toxin enhances sensitivity to NMDA, possibly via its actions on inhibitory G-proteins. RP DURCAN, MJ (reprint author), NIAAA,DICBR,CLIN STUDIES LAB,BLDG 10,ROOM 3C102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 9 Z9 9 U1 0 U2 0 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 MAY 17 PY 1991 VL 197 IS 2-3 BP 209 EP 211 DI 10.1016/0014-2999(91)90523-S PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FT006 UT WOS:A1991FT00600015 PM 1655474 ER PT J AU PERERA, FP RALL, DP WEINSTEIN, IB AF PERERA, FP RALL, DP WEINSTEIN, IB TI CARCINOGENESIS MECHANISMS - THE DEBATE CONTINUES - REPLY SO SCIENCE LA English DT Letter ID ARSENIC-EMITTING SMELTER; LUNG-CANCER MORTALITY; RISK ASSESSMENT; DNA ADDUCTS; MEN; POLAND C1 NIEHS,WASHINGTON,DC 20015. COLUMBIA UNIV,CTR COMPREHENS CANC,NEW YORK,NY 10032. NATL TOXICOL PROGRAM,WASHINGTON,DC 20015. RP PERERA, FP (reprint author), COLUMBIA UNIV,SCH PUBL HLTH,60 HAVEN AVE,NEW YORK,NY 10032, USA. NR 26 TC 5 Z9 5 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 MAY 17 PY 1991 VL 252 IS 5008 BP 903 EP 904 DI 10.1126/science.252.5008.903 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM040 UT WOS:A1991FM04000004 PM 17843206 ER PT J AU STEENLAND, K STAYNER, L GREIFE, A HALPERIN, W HAYES, R HORNUNG, R NOWLIN, S AF STEENLAND, K STAYNER, L GREIFE, A HALPERIN, W HAYES, R HORNUNG, R NOWLIN, S TI MORTALITY AMONG WORKERS EXPOSED TO ETHYLENE-OXIDE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SISTER-CHROMATID EXCHANGES; COHORT; CANCER AB Background. Ethylene oxide is a sterilant gas that causes leukemia and other cancers in animals. Studies in Sweden have shown an excess of leukemia and stomach cancer in humans exposed to ethylene oxide, but other studies have generally failed to confirm these findings. Methods. We conducted a study of mortality in 18,254 U.S. workers exposed to ethylene oxide at 14 plants producing sterilized medical supplies and spices. The subjects averaged 4.9 years of exposure to the gas and 16 years of follow-up. The exposure levels in recent years averaged 4.3 ppm (eight-hour time-weighted adjusted exposure) for sterilizer operators and 2.0 ppm for other workers. The levels in earlier years are likely to have been several times higher. Mortality in this cohort was compared with that in the general U.S. population. Results. Overall there was no significant increase in mortality from any cause in the study cohort. The standardized mortality ratios (SMRs) were 0.97 for leukemia (95 percent confidence interval, 0.52 to 1.67; 13 deaths observed), 1.06 for all hematopoietic cancers (95 percent confidence interval, 0.75 to 1.47; 36 deaths), and 0.94 for stomach cancer (95 percent confidence interval, 0.45 to 1.70; 11 deaths). Analyses according to job category and according to the duration of exposure showed no excess in cancers, as compared with the rate in the general population, but there was a significant trend toward increased mortality with increasing lengths of time since the first exposure for all hematopoietic cancers. The rate of death from hematopoietic cancer (especially non-Hodgkin's lymphoma) was significantly increased among men (SMR, 1.55; 27 deaths). Mortality from leukemia in recent years (1985 through 1987) was significantly increased among men (SMR, 3.45; 5 deaths). Conclusions. For the entire cohort, there was no increase in mortality from hematopoietic cancer. There was a slight but significant increase among men, however. Among men and women combined, there was a trend toward an increased risk of death from hematopoietic cancer with increasing lengths of time since the first exposure to ethylene oxide. C1 NCI,BETHESDA,MD 20892. RP STEENLAND, K (reprint author), NIOSH,R-13,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. NR 32 TC 80 Z9 81 U1 3 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 16 PY 1991 VL 324 IS 20 BP 1402 EP 1407 DI 10.1056/NEJM199105163242004 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA FL125 UT WOS:A1991FL12500004 PM 2020295 ER PT J AU COHEN, JI AF COHEN, JI TI POSTTRANSPLANTATION LYMPHOPROLIFERATIVE DISORDER AND OKT3 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID EPSTEIN-BARR-VIRUS; ANTIBODY RP COHEN, JI (reprint author), NIH,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 16 PY 1991 VL 324 IS 20 BP 1438 EP 1438 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FL125 UT WOS:A1991FL12500020 ER PT J AU STEIN, PD ALAVI, A GOTTSCHALK, A HALES, CA SALTZMAN, HA VREIM, CE WEG, JG AF STEIN, PD ALAVI, A GOTTSCHALK, A HALES, CA SALTZMAN, HA VREIM, CE WEG, JG TI USEFULNESS OF NONINVASIVE DIAGNOSTIC-TOOLS FOR DIAGNOSIS OF ACUTE PULMONARY-EMBOLISM IN PATIENTS WITH A NORMAL CHEST RADIOGRAPH SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB The value of bedside examination and noninvasive tests in the diagnosis of acute pulmonary embolism (PE) among patients with a normal chest radiograph was investigated. Normal chest radiographs were present in 20 of 260 patients (8%) with acute PE and in 113 of 642 (18%) with suspected acute PE, in whom the diagnosis was excluded. A partial pressure of oxygen in arterial blood less-than-or-equal-to 70 mm Hg in a dyspneic patient with a normal chest radiograph was more often seen among patients with PE (9 of 17, 53%) than among patients in whom PE was excluded (18 of 93, 19%; p < 0.01). However, no combinations of blood gases, signs and symptoms were strictly diagnostic. High probability ventilation/perfusion scans among patients with a normal chest radiograph were indicative of PE in only 6 of 9 patients (67%). Among patients with low-probability ventilation/perfusion scans, 8 of 47 (17%) had PE. This study showed that the combination of dyspnea and hypoxia in a patient with a normal chest radiograph is a useful clue to the diagnosis of PE. Although intuition suggested that ventilation/perfusion scans would yield better results in patients with a normal chest radiograph, the ability to diagnose PE by ventilation/perfusion scans in this subset of patients was not enhanced, except by a reduction of the percentage of patients with intermediate probability scans. C1 UNIV PENN,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NHLBI,BETHESDA,MD 20892. MICHIGAN STATE UNIV,E LANSING,MI 48824. DUKE UNIV,DURHAM,NC 27706. UNIV MICHIGAN,DETROIT,MI. RP STEIN, PD (reprint author), HENRY FORD HOSP,INST HEART & VASC,2799 W GRAND BLVD,DETROIT,MI 48202, USA. FU NHLBI NIH HHS [N01-HR-34007, N01-HR-34009, N01-HR-34008] NR 4 TC 47 Z9 47 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 MAY 15 PY 1991 VL 67 IS 13 BP 1117 EP 1120 DI 10.1016/0002-9149(91)90875-L PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FL100 UT WOS:A1991FL10000014 PM 2024602 ER PT J AU FRIEDMAN, DR DUBIN, N AF FRIEDMAN, DR DUBIN, N TI CASE-CONTROL EVALUATION OF BREAST-CANCER SCREENING EFFICACY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BREAST NEOPLASMS; EPIDEMIOLOGIC METHODS; MASS SCREENING ID SELF-EXAMINATION; PHYSICIAN EXAMINATIONS; CERVICAL-CANCER; MORTALITY; REDUCTION; PROGRAM; MAMMOGRAPHY; DEFINITION; DIAGNOSIS; PROJECT AB The feasibility and validity of using case-control methods to evaluate the efficacy of breast cancer screening were investigated using data from the Health Insurance Plan of Greater New York Breast Cancer Screening Trial. Women who died of breast cancer were compared with individually matched controls of the same age who had equal or greater survival times. To minimize the effects of self-selection bias, most analyses focused on the 95 cases and 380 matched controls who had been screened at least once and for whom covariate data were available. A statistically significant effect for being screened more than once versus being screened once, uncorrected for healthy-screenee bias, was found (odds ratio = 0.13, p < 0.001). After correction for healthy-screenee bias, the effect was not statistically significant (odds ratio = 0.54, p = 0.15). Possible explanations for this statistical nonsignificance are: 1) correction for healthy-screenee bias entails loss of power and 2) the correction procedure used may, under some circumstances, result in bias toward the null hypothesis. Further research into means of eliminating healthy-screenee bias is needed to improve the applicability of case-control methods to the evaluation of screening efficacy. C1 NYU,MED CTR,INST ENVIRONM MED,EPIDEMIOL & BIOSTAT LAB,341 E 25TH ST,NEW YORK,NY 10010. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-13343, CA-16087, CA-43885] NR 31 TC 44 Z9 44 U1 1 U2 4 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 1991 VL 133 IS 10 BP 974 EP 984 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FP558 UT WOS:A1991FP55800002 PM 2035508 ER PT J AU CHU, KC CONNOR, RJ AF CHU, KC CONNOR, RJ TI ANALYSIS OF THE TEMPORAL PATTERNS OF BENEFITS IN THE HEALTH-INSURANCE-PLAN-OF-GREATER-NEW-YORK TRIAL BY STAGE AND AGE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BREAST NEOPLASMS; DATA INTERPRETATION, STATISTICAL; MAMMOGRAPHY; MODELS, STATISTICAL; NEOPLASMS, PREVENTION AND CONTROL ID BREAST-CANCER MORTALITY; MODEL AB Reductions in breast cancer mortality in the Health Insurance Plan of Greater New York trial are examined by age at entry and stage at diagnosis using a stage shift cancer screening model. The results indicate that for women aged 40-49 years at entry, benefits are associated with an internal stage shift of stage 1 cancers that have a prognosis poorer than the usual stage 1 cancers. Further, the results indicate that after 18 years of follow-up, of the reduction of 16 fewer deaths in the intervention group, 12-15 of the deaths are related to this internal shift. Given that stage 1 cases inherently have relatively good survival, the time required to see the screening benefit is substantial. For women aged 50-64 years at entry, the results suggest that benefits are associated primarily with shifts to or within stage 1. Further, the results indicate that after 6 years, of the reduction of 31 fewer deaths in the intervention group, 22 of the deaths are related to external shifts to stage 1. Given that stage 2 cancers have poorer survival than stage 1 cancers, screening benefit is seen sooner for the older cohort than for the younger cohort. C1 NCI,BIOMETRY BRANCH,BETHESDA,MD 20892. RP CHU, KC (reprint author), NCI,EARLY DETECT BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 17 Z9 17 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 1991 VL 133 IS 10 BP 1039 EP 1049 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FP558 UT WOS:A1991FP55800009 PM 2035504 ER PT J AU ENGSTROM, RE HOLLAND, GN NUSSENBLATT, RB JABS, DA AF ENGSTROM, RE HOLLAND, GN NUSSENBLATT, RB JABS, DA TI CURRENT PRACTICES IN THE MANAGEMENT OF OCULAR TOXOPLASMOSIS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CLINDAMYCIN; PYRIMETHAMINE; INFECTION; UVEITIS AB To determine current practices in the management of ocular toxoplasmosis, 72 of 85 uveitis specialists (85%) in the American Uveitis Society completed a detailed questionnaire. Questions involved the indications for beginning treatment, choice of antiparasitic/antimicrobial agents, and experience with treatment of ocular toxoplasmosis in special situations including pregnancy, neonatal infections, and immunocompromised patients. Most of the respondents treat patients whose visual acuity had decreased to worse than 20/200, lesions located in the peripapillary, perifoveal, or maculopapillary bundle regions, and lesions associated with severe vitreous inflammation. Most would not treat patients who retained visual acuity of 20/20, lesions located in the far peripheral retina, or lesions associated with only trace to mild vitreous inflammation. Treatment of other combinations of factors remains controversial. Eight different antimicrobial drugs are used in various combinations for lesions threatening the macula or optic nerve head. Systemic corticosteroids are used by 59 of 62 respondents (95%) as part of their initial treatment regimen. The most commonly used regimens are pyrimethamine/sulfadiazine/corticosteroids (20 of 62 [32%]) and pyrimethamine/sulfadiazine/clindamycin/corticosteroids (17 of 62 [27%]). Adjunctive therapies (photocoagulation, cryotherapy, or vitrectomy) have been used by 20 of 60 respondents (33%). Most alter treatment during pregnancy, in newborn patients, and in patients with the acquired immunodeficiency syndrome. C1 UNIV CALIF LOS ANGELES,CTR OCULAR INFLAMMATORY DIS,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT OPHTHALMOL,LOS ANGELES,CA 90024. NEI,BETHESDA,MD. JOHNS HOPKINS UNIV HOSP,WILMER OPHTHALMOL INST,BALTIMORE,MD 21205. NR 35 TC 69 Z9 73 U1 1 U2 1 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY 15 PY 1991 VL 111 IS 5 BP 601 EP 610 PG 10 WC Ophthalmology SC Ophthalmology GA FK067 UT WOS:A1991FK06700012 PM 2021170 ER PT J AU BLOCK, G HENSON, DE LEVINE, M AF BLOCK, G HENSON, DE LEVINE, M TI VITAMIN-C - A NEW LOOK SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID ASCORBIC-ACID; CELLS; TUMOR; BIOSYNTHESIS; REPLICATION; DEFICIENCY; TOXICITY; VIRUS; MICE AB A conference recently held at the National Institutes of Health brought together researchers in many disciplines to discuss the biologic functions of vitamin C and the possible relation between vitamin C and cancer. Recent research indicates that vitamin C has many important functions, including not simply the prevention of scurvy but also the synthesis of essential proteins and hormones and the prevention of damage from free radicals generated by cigarette smoke and activated neutrophils. Antibacterial and antiviral actions also have been described. The results of epidemiologic studies suggest that vitamin C has a role in reducing the incidence of cancer, and several studies conducted in laboratory animals found that vitamin C reduced tumor incidence or severity. Vitamin C has been reported to reduce the toxicity of therapeutic agents such as adriamycin and radiotherapy. Some patient groups are at increased risk for having low plasma levels of vitamin C, and the assessment of these levels in such patients is warranted. C1 NIDDKD,BETHESDA,MD 20892. RP BLOCK, G (reprint author), NCI,EPN ROOM 313,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Block, Gladys/E-3304-2010 NR 20 TC 30 Z9 30 U1 2 U2 9 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 15 PY 1991 VL 114 IS 10 BP 909 EP 910 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FL650 UT WOS:A1991FL65000014 PM 2014955 ER PT J AU ROSS, RS LI, AC HOEG, JM SCHUMACHER, UK DEMOSKY, SJ BREWER, HB AF ROSS, RS LI, AC HOEG, JM SCHUMACHER, UK DEMOSKY, SJ BREWER, HB TI APOLIPOPROTEIN-B UPSTREAM SUPPRESSOR SITE - IDENTIFICATION OF AN ELEMENT WHICH CAN DECREASE APOLIPOPROTEIN-B TRANSCRIPTION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CORONARY-ARTERY DISEASE; REGULATORY ELEMENTS; MESSENGER-RNA; SEQUENCE-ANALYSIS; GENE-EXPRESSION; STOP CODON; DNA; PROMOTER; ENHANCER; PROTEINS C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 45 TC 3 Z9 3 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 15 PY 1991 VL 176 IS 3 BP 1116 EP 1122 DI 10.1016/0006-291X(91)90400-2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FM750 UT WOS:A1991FM75000027 PM 2039496 ER PT J AU KOWATCH, MA ROTH, GS AF KOWATCH, MA ROTH, GS TI ALPHA1-ADRENERGIC AND MUSCARINIC-CHOLINERGIC STIMULATED INOSITOL TRISPHOSPHATE PRODUCTION MAY PROCEED THROUGH DIFFERENT POSTRECEPTOR SIGNAL TRANSDUCTION PATHWAYS IN PAROTID ACINI SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOSPHOLIPID HYDROLYSIS; PHOSPHATES; CELLS; RELEASE; LEVEL RP KOWATCH, MA (reprint author), FRANCIS SCOTT KEY MED CTR,NIH,NIA,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224, USA. NR 18 TC 8 Z9 8 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 MAY 15 PY 1991 VL 176 IS 3 BP 1291 EP 1297 DI 10.1016/0006-291X(91)90426-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FM750 UT WOS:A1991FM75000053 PM 1645540 ER PT J AU CHAKRABORTI, PK SIMONS, SS AF CHAKRABORTI, PK SIMONS, SS TI ASSOCIATION OF HEAT-SHOCK PROTEIN-90 WITH THE 16KDA STEROID BINDING CORE FRAGMENT OF RAT GLUCOCORTICOID RECEPTORS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DNA-BINDING; COMPLEX; DOMAIN; PHOSPHOPROTEIN; TRANSFORMATION; PROTEOLYSIS; COMPONENT; AFFINITY; ARSENITE; REGION C1 NIDDK,STEROID HORMONES SECT,BLDG 8,RM B2A07,BETHESDA,MD 20892. NR 33 TC 28 Z9 28 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 MAY 15 PY 1991 VL 176 IS 3 BP 1338 EP 1344 DI 10.1016/0006-291X(91)90433-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FM750 UT WOS:A1991FM75000060 PM 2039516 ER PT J AU SCAVO, LM SERRANO, J ROTH, J DEPABLO, F AF SCAVO, LM SERRANO, J ROTH, J DEPABLO, F TI GENES FOR THE INSULIN-RECEPTOR AND THE INSULIN-LIKE GROWTH FACTOR-I RECEPTOR ARE EXPRESSED IN THE CHICKEN-EMBRYO BLASTODERM AND THROUGHOUT ORGANOGENESIS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TYROSINE KINASE; PHOSPHORYLATION; PEPTIDES; ONTOGENY; DOMAINS; FAMILY RP SCAVO, LM (reprint author), NIDDKD,DIABET BRANCH,RECEPTORS & HORMONE ACTION SECT,BLDG 10,ROOM 8S 243,BETHESDA,MD 20892, USA. NR 24 TC 42 Z9 42 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 MAY 15 PY 1991 VL 176 IS 3 BP 1393 EP 1401 DI 10.1016/0006-291X(91)90441-9 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FM750 UT WOS:A1991FM75000068 PM 1710113 ER PT J AU PLOUZEK, CA WATANABE, S CHOU, JY AF PLOUZEK, CA WATANABE, S CHOU, JY TI CLONING AND EXPRESSION OF A NEW PREGNANCY-SPECIFIC BETA-1-GLYCOPROTEIN MEMBER SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ANTIGEN GENE FAMILY; CARCINOEMBRYONIC ANTIGEN; SODIUM-BUTYRATE; GLYCOPROTEIN GENES; MOLECULAR-CLONING; CDNA; SP1; MALIGNANCIES; SUBFAMILY; PROTEINS C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 25 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 15 PY 1991 VL 176 IS 3 BP 1532 EP 1538 DI 10.1016/0006-291X(91)90461-F PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FM750 UT WOS:A1991FM75000088 PM 1840485 ER PT J AU JACOBSON, KA TRIVEDI, BK CHURCHILL, PC WILLIAMS, M AF JACOBSON, KA TRIVEDI, BK CHURCHILL, PC WILLIAMS, M TI NOVEL THERAPEUTICS ACTING VIA PURINE RECEPTORS SO BIOCHEMICAL PHARMACOLOGY LA English DT Editorial Material ID ADENOSINE RECEPTORS; RAT-KIDNEY; ANTAGONISTS; INHIBITION; AGONISTS; INVIVO; BLOOD; THEOPHYLLINE; GRANULOCYTES; DERIVATIVES C1 ABBOTT LABS,ABBOTT PK,IL 60064. WARNER LAMBERT PARKE DAVIS,DIV PHARMACEUT RES,ANN ARBOR,MI 48105. WAYNE STATE UNIV,DEPT PHYSIOL,DETROIT,MI 48201. RP JACOBSON, KA (reprint author), NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 69 TC 52 Z9 52 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 15 PY 1991 VL 41 IS 10 BP 1399 EP 1410 DI 10.1016/0006-2952(91)90555-J PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FF861 UT WOS:A1991FF86100002 PM 2018549 ER PT J AU MORENOSANCHEZ, R HOGUE, BA BRAVO, C NEWMAN, AH BASILE, AS CHIANG, PK AF MORENOSANCHEZ, R HOGUE, BA BRAVO, C NEWMAN, AH BASILE, AS CHIANG, PK TI INHIBITION OF SUBSTRATE OXIDATION IN MITOCHONDRIA BY THE PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR LIGAND AHN-086 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID BINDING-SITES; RAT-BRAIN; SUBCELLULAR-DISTRIBUTION; H-3 RO5-4864; RO 5-4864; LOCALIZATION; DEHYDROGENASE; TRANSPORT; MEMBRANE; KIDNEY AB The effects, of the benzodiazepines RO5-4864, AHN 086, PK 11195 and clonazepam on respiration of mitochondria from heart, kidney, and liver were studied. ADP-stimulated respiration of heart mitochondria was the most sensitive to inhibition by AHN 086; clonazepam was not inhibitory. Several respiratory chain segment activities of submitochondrial particles were insensitive to AHN 086, except for NADH oxidase which was partially inhibited. However, in contrast to submitochondrial particles, the succinate-cytochrome c oxidoreductase activity in intact mitochondria was inhibited by AHN 086, suggesting an effect at the substrate transport level. Phosphate-induced, succinate-dependent swelling was also inhibited by AHN 086 it was not affected by clonazepam. Uncoupled ATP hydrolysis was partially inhibited by RO5-4864, AHN 086, and clonazepam. It is suggested that there is an unspecific inhibition of NADH oxidase and ATP hydrolysis by these benzodiazepines and a specific inhibition on oxidizable substrate transport by the peripheral-type benzodiazepine AHN 086. C1 NIH,GERONTOL RES CTR,BALTIMORE,MD 21224. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NIDDK,BETHESDA,MD 20892. RP MORENOSANCHEZ, R (reprint author), INST NACL CARDIOL,DEPT BIOQUIM,JUAN BADIANO 1 TLALPAN,MEXICO CITY 14080,DF,MEXICO. OI Moreno-Sanchez, Rafael/0000-0002-9587-7184 NR 40 TC 35 Z9 35 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 15 PY 1991 VL 41 IS 10 BP 1479 EP 1484 DI 10.1016/0006-2952(91)90564-L PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FF861 UT WOS:A1991FF86100011 PM 1850277 ER PT J AU BURKE, TR LI, ZH BOLEN, JB CHAPEKAR, M GANG, Y GLAZER, RI RICE, KC MARQUEZ, VE AF BURKE, TR LI, ZH BOLEN, JB CHAPEKAR, M GANG, Y GLAZER, RI RICE, KC MARQUEZ, VE TI EXAMINATION OF THE POSSIBLE MEDIATION OF ANTINEOPLASTIC EFFECTS OF OPIATES THROUGH THE INHIBITION OF TYROSINE-SPECIFIC PROTEIN-KINASES SO BIOCHEMICAL PHARMACOLOGY LA English DT Note ID TUMOR C1 NIDDKD,MED BRANCH,BETHESDA,MD 20892. NIDDKD,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. RP BURKE, TR (reprint author), NIDDKD,MED CHEM LAB,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 17 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 15 PY 1991 VL 41 IS 10 BP R17 EP R20 DI 10.1016/0006-2952(91)90554-I PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FF861 UT WOS:A1991FF86100001 PM 2018548 ER PT J AU ISSARAGRISIL, S SRIRATANASATAVORN, C PIANKIJAGUM, A VANNASAENG, S PORAPAKKHAM, Y LEAVERTON, PE KAUFMAN, DW ANDERSON, TE SHAPIRO, S YOUNG, NS AF ISSARAGRISIL, S SRIRATANASATAVORN, C PIANKIJAGUM, A VANNASAENG, S PORAPAKKHAM, Y LEAVERTON, PE KAUFMAN, DW ANDERSON, TE SHAPIRO, S YOUNG, NS TI INCIDENCE OF APLASTIC-ANEMIA IN BANGKOK SO BLOOD LA English DT Article ID POPULATION C1 MAHIDOL UNIV,FAC PUBL HLTH,DEPT BIOSTAT,BANGKOK 10700,THAILAND. UNIV S FLORIDA,COLL PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,TAMPA,FL 33620. BOSTON UNIV,SCH MED,SLONE EPIDEMIOL UNIT,BOSTON,MA 02118. NHLBI,CLIN HEMATOL BRANCH,CELL BIOL SECT,BETHESDA,MD 20892. RP ISSARAGRISIL, S (reprint author), SIRIRAJ HOSP,FAC MED,DEPT MED,DIV HEMATOL,BANGKOK 10700,THAILAND. OI Issaragrisil, Surapol/0000-0002-8924-0646 FU NHLBI NIH HHS [HL 35068] NR 16 TC 42 Z9 45 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 MAY 15 PY 1991 VL 77 IS 10 BP 2166 EP 2168 PG 3 WC Hematology SC Hematology GA FM262 UT WOS:A1991FM26200013 PM 2029577 ER PT J AU NIENHUIS, AW MCDONAGH, KT BODINE, DM AF NIENHUIS, AW MCDONAGH, KT BODINE, DM TI GENE-TRANSFER INTO HEMATOPOIETIC STEM-CELLS SO CANCER LA English DT Article; Proceedings Paper CT SYMP ON A A VISIONARY ASSESSMENT OF THE SCIENTIFIC, CLINICAL, AND ECONOMICAL IMPLICATIONS OF HEMATOPOIETIC GROWTH FACTORS CY AUG 31, 1990 CL SEATTLE, WA ID RETROVIRAL VECTORS; COMBINATION; EXPRESSION AB The ability to reliably transfer genes into hematopoietic stem cells with long-term repopulating potential and to selectively express such genes would allow genetic therapy for diseases such as sickle cell anemia and immunologic deficiencies due to T-cell defects, including acquired immune deficiency syndrome (AIDS). Understanding the biology of the hematopoietic stem cell is a key element in realizing the full therapeutic potential of gene insertion strategies. Current techniques have efficiency rates of gene insertion of approximately 10% to 20% into murine stem cells and 1% to 5% into primate stem cells. Many challenges, some biologic and some logistic, remain before gene transfer protocols that are successful in the mouse model can be extended to humans. RP NIENHUIS, AW (reprint author), NHLBI,CLIN HEMATOL BRANCH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. NR 25 TC 31 Z9 34 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 1991 VL 67 IS 10 SU S BP 2700 EP 2704 DI 10.1002/1097-0142(19910515)67:10+<2700::AID-CNCR2820671705>3.0.CO;2-3 PG 5 WC Oncology SC Oncology GA FJ925 UT WOS:A1991FJ92500004 PM 2015571 ER PT J AU VISTICA, DT SKEHAN, P SCUDIERO, D MONKS, A PITTMAN, A BOYD, MR AF VISTICA, DT SKEHAN, P SCUDIERO, D MONKS, A PITTMAN, A BOYD, MR TI TETRAZOLIUM-BASED ASSAYS FOR CELLULAR VIABILITY - A CRITICAL-EXAMINATION OF SELECTED PARAMETERS AFFECTING FORMAZAN PRODUCTION SO CANCER RESEARCH LA English DT Article ID CHEMICAL MODIFICATION; GROWTH; SULFHYDRYL; MEMBRANES; LINES AB The hydrogen acceptor 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetra-zolium bromide (MTT) is commonly utilized to estimate cellular viability in drug screening protocols. The present investigation was prompted, in part, by observations that reduction of MTT to its colored reaction product, MTT formazan, varied between cell lines and with culture age. A correlation was established between the D-glucose concentration of the culture medium at the time of assay and the production of MTT formazan for cell lines representing seven tumor histologies. A decrease in the concentration of D-glucose from culture medium was accompanied by a decrease in MTT specific activity (MTT formazan/mu-g cell protein) for a number of cell lines. Cells which extensively metabolized D-glucose exhibited the greatest reduction in MTT specific activity. Further evidence that the D-glucose concentration of the culture medium played an important role in MTT reduction was provided by experiments which demonstrated that transfer of cells to a glucose-free medium (L-15) was accompanied by an immediate decrease in MTT reduction which was pH independent. These studies suggested that cellular transport and constant metabolism of glucose were required for maximum MTT reduction. Decreases in the cellular concentration of the reduced pyridine nucleotides NADH and NADPH were accompanied by concomitant decreases in MTT formazan production. MTT formazan varied significantly among cell lines in both the kinetics of its formation and the degree of saturability exhibited. Apparent IC50 values for Adriamycin varied, in a cell line-specific manner, with MTT exposure time. These results indicate that MTT specific activity is significantly influenced by a number of parameters and suggest that assay conditions should be established which minimize their effects. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. PROGRAM RESOURCES INC,FREDERICK,MD 21702. RP VISTICA, DT (reprint author), NCI,FREDERICK CANC RES & DEV CTR,POB B,BLDG 1052,ROOM 121,FREDERICK,MD 21702, USA. NR 20 TC 424 Z9 438 U1 3 U2 29 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1991 VL 51 IS 10 BP 2515 EP 2520 PG 6 WC Oncology SC Oncology GA FK910 UT WOS:A1991FK91000002 PM 2021931 ER PT J AU BOCK, SN CAMERON, RB KRAGEL, P MULE, JJ ROSENBERG, SA AF BOCK, SN CAMERON, RB KRAGEL, P MULE, JJ ROSENBERG, SA TI BIOLOGICAL AND ANTITUMOR EFFECTS OF RECOMBINANT HUMAN MACROPHAGE COLONY-STIMULATING FACTOR IN MICE SO CANCER RESEARCH LA English DT Article ID MARROW-DERIVED MACROPHAGES; MELANOMA LIVER METASTASES; MURINE MACROPHAGES; FACTOR CSF-1; CYTO-TOXICITY; GROWTH-FACTOR; TUMORICIDAL ACTIVITY; MONOCLONAL-ANTIBODY; PROGENITOR CELLS; INDUCTION AB The administration of recombinant human macrophage colony-stimulating factor (M-CSF) i.p. in doses of 25 or 100-mu-g twice daily for 5 consecutive days to non-tumor-bearing C57BL/6 mice resulted in a dose-dependent infiltration of mononuclear cells in the livers but not the lungs of these treated animals. Immunohistochemical examination of fixed liver tissue with the murine macrophage-specific monoclonal antibody, F4/80, revealed a >5-fold increase in the number of hepatic macrophages. Quantification of F4/80-positive cells in a mononuclear single cell suspension derived from liver revealed a > 25-fold expansion in the number of hepatic macrophages compared to control mice. These cells were then tested in 18-h Cr-51 release assays for tumoricidal activity, after an 18-h incubation with orwithout gamma-interferon, against cultured P815 targets. Significant tumor cell lysis by these liver-associated mononuclear cells occurred, which was enhanced by gamma-interferon preincubation. The systemic administration of M-CSF alone at high dose had no antitumor impact in vivo against 3-day pulmonary metastases from the MCA-203 sarcoma and B16 melanoma or hepatic metastases from the B16 melanoma or MCA-105, -203, or -207 sarcomas. Although the systemic administration of M-CSF in combination with tumor-specific monoclonal antibody had no effect on 3-day pulmonary metastases from the B16 melanoma, significant reductions in liver metastases were seen. These murine studies demonstrate the biological activity of recombinant human M-CSF in vivo and suggest that the administration of this cytokine in combination with specific monoclonal antibody may be useful in the treatment of patients with metastatic disease at sites of monocyte/macrophage accumulation. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NR 38 TC 46 Z9 46 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1991 VL 51 IS 10 BP 2649 EP 2654 PG 6 WC Oncology SC Oncology GA FK910 UT WOS:A1991FK91000024 PM 2021943 ER PT J AU THOMPSON, EW NAKAMURA, S SHIMA, TB MELCHIORI, A MARTIN, GR SALAHUDDIN, SZ GALLO, RC ALBINI, A AF THOMPSON, EW NAKAMURA, S SHIMA, TB MELCHIORI, A MARTIN, GR SALAHUDDIN, SZ GALLO, RC ALBINI, A TI SUPERNATANTS OF ACQUIRED IMMUNODEFICIENCY SYNDROME-RELATED KAPOSIS-SARCOMA CELLS INDUCE ENDOTHELIAL-CELL CHEMOTAXIS AND INVASIVENESS SO CANCER RESEARCH LA English DT Article ID FIBROBLAST GROWTH-FACTOR; RECONSTITUTED BASEMENT-MEMBRANE; CAPILLARY-LIKE STRUCTURES; LONG-TERM CULTURE; TUMOR-CELLS; PLASMINOGEN-ACTIVATOR; DNA-SYNTHESIS; EXTRACELLULAR-MATRIX; HOMOSEXUAL MEN; EARLY LESIONS AB Kaposi's sarcoma (KS) in general, and acquired immunodeficiency syndrome-related KS (AIDS-KS) in particular, is a highly invasive and intensely angiogenic neoplasm of unknown cellular origin. We have recently established AIDS-KS cells in long term culture and reported the development of KS-like lesions in nude mice inoculated with these cells. Here, we have examined the in vitro invasiveness of basement membrane by AIDS-KS cells, as well as the effect(s) of their supernatants on the migration and invasiveness of human vascular endothelial cells. AIDS-KS cells were highly invasive in the Boyden chamber invasion assau amd formed invasive, branching colonies in a 3-dimensional gel (Matrigel). Normal endothelial cells form tube-like structures on Matrigel. AIDS-KS cell-conditioned media induced endothelial cells to form invasive clusters in addition to tubes. KS-cell-conditioned media, when placed in the lower compartment of the Boyden chamber, stimulated the migration of human and bovine vascular endothelial cells across filters coated with either small amounts of collagen IV (chemotaxis) or a Matrigel barrier (invasion). Basic fibroblast growth factor could also induce endothelial cell chemotaxis and invasion in these assays. However, when antibodies to basic fibroblast growth factor were used the invasive activity induced by the AIDS-KS-cell-conditioned media was only marginally inhibited, suggesting that the large quantities of basic fibroblast growth factor-like material released by the AIDS-KS cells are not the main mediators of this effect. Specific inhibitors of laminin and collagenase IV action, which represent critical determinants of basement membrane invasion, blocked the invasiveness of the AIDS-KS cell-activated endothelial cells in these assays. These data indicate that KS cells appear to be of smooth muscle origin but secrete a potent inducer of endothelial cell chemotaxis and invasiveness which could be responsible for angiogenesis and the resulting highly vascularized lesions. These assays appear to be model to study the invasive spread and angiogenic capacity of human AIDS-related KS and should prove useful in the identification of molecular mediators and potential inhibitors of neoplastic neovascularization. C1 IST NAZL RIC CANC,VIALE BENEDETTO XV 10,I-16132 GENOA,ITALY. NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Thompson, Erik/A-1425-2009 OI Thompson, Erik/0000-0002-9723-4924 NR 74 TC 64 Z9 64 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1991 VL 51 IS 10 BP 2670 EP 2676 PG 7 WC Oncology SC Oncology GA FK910 UT WOS:A1991FK91000026 PM 2021945 ER PT J AU WATANABE, T PRATT, RM AF WATANABE, T PRATT, RM TI EFFECTS OF RETINOIC ACID ON EMBRYONIC-DEVELOPMENT OF MICE IN CULTURE SO EXPERIENTIA LA English DT Article DE ALL-TRANS-RETINOIC ACID; WHOLE EMBRYO CULTURE; MOUSE EMBRYOS; CRANIOFACIAL DEVELOPMENT; MESENCHYMAL CELLS; PALATAL PROCESSES ID NEURAL CREST CELLS; 13-CIS-RETINOIC ACID; MESENCHYMAL CELLS; PALATAL SHELVES; TERATOGENICITY; ORGANOGENESIS; ISOTRETINOIN; PROLIFERATION; DEFECTS; BINDING AB The effects of all-trans-retinoic acid (RA) (tretinoin) on the craniofacial development of mouse embryos were examined using whole embryo culture. In day 8 embryos cultured for 48 h, embryonic growth was inhibited concentration-dependently by all-trans-RA treatment. Most of the treated embryos exhibited hypoplasia of the primary palatal processes and a reduction in the development of the first visceral arches. In day 10 embryos cultured for 48 h, although embryonic growth was not inhibited at any concentrations of all-trans-RA, median cleft lip (93%), hypoplasia of the primary palatal processes (37%) and limb reduction deformities (48%) occurred commonly. Furthermore, RA treatment greatly reduced the size of the secondary palatal processes. The incorporation of H-3-thymidine in the treated maxillary processes was decreased to 65% of the control value at 1.0 x 10(-7) M all-trans-RA. These findings indicate that all-trans-RA is teratogenic in mouse whole embryo culture. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP WATANABE, T (reprint author), YAMAGATA UNIV,SCH MED,DEPT HYG & PREVENT MED,YAMAGATA 99023,JAPAN. NR 29 TC 9 Z9 9 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 0014-4754 J9 EXPERIENTIA JI Experientia PD MAY 15 PY 1991 VL 47 IS 5 BP 493 EP 497 DI 10.1007/BF01959953 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FP338 UT WOS:A1991FP33800034 PM 2044705 ER PT J AU FALES, HM PU, QL MASON, RT PANNELL, LK AF FALES, HM PU, QL MASON, RT PANNELL, LK TI THE ION TRAP MASS-SPECTRUM OF SULFUR SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY AND ION PROCESSES LA English DT Article ID SPECTROMETER AB The mass spectrum of sulfur (S8) obtained with the ion trap mass spectrometer is compared with that obtained using an E-B spectrometer. Each ion in the spectrum is examined for fragmentation and the vapor shown to consist mostly of the S8 oligomer. The chemical ionization spectra using methane, isobutane, ammonia, and water are also examined and an estimate made of the proton affinity of S8. Using methane, most of the fragment ions are derived from (M + C2H5)+ rather than (M + H)+. C1 NIDDKD,BETHESDA,MD 20892. RP FALES, HM (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 15 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1176 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. Ion Process. PD MAY 15 PY 1991 VL 106 BP 273 EP 281 DI 10.1016/0168-1176(91)85023-F PG 9 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA FP130 UT WOS:A1991FP13000016 ER PT J AU GAIL, MH PLUDA, JM RABKIN, CS BIGGAR, RJ GOEDERT, JJ HORM, JW SONDIK, EJ YARCHOAN, R BRODER, S AF GAIL, MH PLUDA, JM RABKIN, CS BIGGAR, RJ GOEDERT, JJ HORM, JW SONDIK, EJ YARCHOAN, R BRODER, S TI PROJECTIONS OF THE INCIDENCE OF NON-HODGKINS-LYMPHOMA RELATED TO ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MEMORIAL HOSPITAL EXPERIENCE; PLACEBO-CONTROLLED TRIAL; WISKOTT-ALDRICH SYNDROME; BURKITT-LIKE LYMPHOMA; HOMOSEXUAL MEN; MALIGNANT-LYMPHOMA; SYNDROME AIDS; CANCER REGISTRY; HIV INFECTION; UNITED-STATES AB Advances in antiretroviral therapy and treatment or prophylaxis against opportunistic infections have resulted in prolongation of the survival of patients with acquired immunodeficiency syndrome (AIDS). Previous research has demonstrated an association between AIDS and risk of non-Hodgkin's lymphoma (NHL). In addition to the approximately 3% of individuals found to have NHL at the time of AIDS onset, other continue to develop NHL following AIDS diagnosis. Data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute demonstrated a sharply increasing incidence of NHL among men in the age range 20-49 years since 1983 in the United States. Based on new data on the risk of NHL following AIDS diagnosis, on estimates of improved survival following AIDS diagnosis, and on projections of future AIDS incidence, we considered four sets of assumptions and estimated the number of AIDS-related NHL cases in 1992 to be between 2900 and 9800. Three of these projections were higher than the estimate of 4700 cases obtained by linear extrapolation of SEER incidence trends. These projections of AIDS-related NHL incidence suggest that between 8% and 27% of all NHL cases that occur in the United States in 1992 will arise as a consequence of infection with the human immunodeficiency virus (HIV), imposing a substantial health care burden. More research into the pathogenesis of lymphoma and new approaches to antiretroviral and antilymphoma therapy will be necessary to prevent and treat this formidable complication of infection with HIV. C1 NCI, DIV CANC PREVENT & CONTROL, SPECIAL POPULAT STUDIES BRANCH, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT, CLIN ONCOL PROGRAM, BETHESDA, MD 20892 USA. NCI, DIV CANC ETIOL, ENVIRONM EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. RP GAIL, MH (reprint author), NCI, DIV CANC ETIOL, BIOSTAT BRANCH, EXECUT PL N, RM 403, BETHESDA, MD 20892 USA. NR 36 TC 124 Z9 124 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD MAY 15 PY 1991 VL 83 IS 10 BP 695 EP 701 DI 10.1093/jnci/83.10.695 PG 7 WC Oncology SC Oncology GA FK865 UT WOS:A1991FK86500011 PM 2023270 ER PT J AU HUANG, FL HUANG, KP AF HUANG, FL HUANG, KP TI INTERACTION OF PROTEIN-KINASE-C ISOZYMES WITH PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHORBOL ESTER-BINDING; RAT-BRAIN; MIXED MICELLES; CALCIUM INTERDEPENDENCIES; MECHANISTIC IMPLICATIONS; 2ND MESSENGERS; ACTIVATION; DIACYLGLYCEROL; EXPRESSION; SUBSTRATE AB Interaction of protein kinase C (PKC) isozymes with phosphatidylinositol 4,5-bisphosphate (PIP2) was investigated by monitoring the changes in the intrinsic fluorescence of the enzyme, the kinase activity, and phorbol ester binding. Incubation of PKC I, II, and III with PIP2 resulted in different rates of quenching of PKC fluorescence and different degrees of inactivation of these enzymes. Other inositol-containing phospholipids such as phosphatidylinositol and phosphatidylinositol 4-phosphate also caused differential rates of quenching of the intrinsic fluorescence of these enzymes. These latter two phospholipids were, however, less potent in the inactivation of PKCs than PIP2. The IC50 of PIP2 were 2, 4, and 11-mu-M for PKC I, II, and III, respectively. Inactivation of PKCs by PIP2 cannot be reversed by extensive dilution of PIP2 with Nonidet P-40 nor by digestion of PIP2 with phospholipase C. Interaction of PIP2 with the various PKC isozymes was greatly facilitated in the presence of Mg2+ or Ca2+ as evidenced by the accelerated quenching of the PKC fluorescence, however, these divalent metal ions protected PKC from the PIP2-induced inactivation. Binding of PIP2 to PKC in the absence of divalent metal ion also caused a reduction of [H-3]phorbol 12,13-dibutyrate binding as a result of reducing the affinity of the enzyme for phorbol ester. Based on gel filtration chromatography, it was estimated that one molecule of PKC interacted with one PIP2 micelle with an aggregation number of 80-90. The PIP2-bound PKC could further interact with phosphatidylserine in the presence of Ca2+ to form a larger complex. Binding of PKC to both PIP2 and phosphatidylserine in the presence of Ca2+ was also evident by changes in the intrinsic fluorescence of PKC. As the interaction of PKC with PIP2, but not with phosphatidylserine, could be enhanced by millimolar concentrations of Mg2+, we propose that PIP2 may be a component of the membrane anchor for PKC under basal physiological conditions when [Ca2+]i is low and Mg2+ is plentiful. Under the in vitro assay conditions, PIP2 could stimulate PKC activity to a level approximately 10-20% of that by diacylglycerol. The stimulatory effect of PIP2 on PKC apparently is not due to binding to the same site recognized by diacylglycerol or phorbol ester, because PIP2 cannot effectively compete with phorbol 12,13-dibutyrate in the binding assay. RP HUANG, FL (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,METAB REGULAT SECT,BLDG 10,RM B1-L400,BETHESDA,MD 20892, USA. NR 48 TC 45 Z9 47 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 MAY 15 PY 1991 VL 266 IS 14 BP 8727 EP 8733 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM038 UT WOS:A1991FM03800017 PM 1851155 ER PT J AU YOSHIMURA, K NAKAMURA, H TRAPNELL, BC DALEMANS, W PAVIRANI, A LECOCQ, JP CRYSTAL, RG AF YOSHIMURA, K NAKAMURA, H TRAPNELL, BC DALEMANS, W PAVIRANI, A LECOCQ, JP CRYSTAL, RG TI THE CYSTIC-FIBROSIS GENE HAS A HOUSEKEEPING-TYPE PROMOTER AND IS EXPRESSED AT LOW-LEVELS IN CELLS OF EPITHELIAL ORIGIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; DEPENDENT PROTEIN-KINASE; CHLORIDE CHANNELS; AIRWAY EPITHELIA; MAMMALIAN-CELLS; DNA; IDENTIFICATION; TRANSCRIPTION; MUTATIONS; ELEMENTS AB Evaluation of the expression of the cystic fibrosis (CF) gene in human epithelial cell lines demonstrated active, but low level, transcription of the gene. Analysis of 3.8 kilobases of genomic sequences 5' to exon 1 of the CF gene demonstrated no TATA promoter element, but a high G + C content, multiple transcription start sites, and several potential Sp1 binding sites. Fragments of 5'-flanking sequences from 2.2 kilobases to as small as 102 base pairs 5' to the major transcription start site supported constitutive reporter gene expression in epithelial cells, but at low levels, and independent of the length of the 5' fragment. CF gene transcription was down-regulated by phorbol myristate acetate. Importantly, evaluation of freshly isolated normal human bronchial cells also demonstrated CF gene transcription at a relatively low rate. Together, these observations suggest that although the normal CF gene promoter has characteristics of a "housekeeping"-type gene, and the gene is expressed at low levels in cells of organs that manifest the clinical disorder "cystic fibrosis," its expression can be modulated transcriptionally, implying a possible therapeutic approach for the disease. C1 TRANSGENE SA,F-67082 STRASBOURG,FRANCE. RP YOSHIMURA, K (reprint author), NHLBI,PULM BRANCH,BLDG 10,RM 6D03,BETHESDA,MD 20892, USA. NR 37 TC 155 Z9 156 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 1991 VL 266 IS 14 BP 9140 EP 9144 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM038 UT WOS:A1991FM03800073 PM 1709163 ER PT J AU MINAMI, Y STAFFORD, FJ LIPPINCOTTSCHWARTZ, J YUAN, LC KLAUSNER, RD AF MINAMI, Y STAFFORD, FJ LIPPINCOTTSCHWARTZ, J YUAN, LC KLAUSNER, RD TI NOVEL REDISTRIBUTION OF AN INTRACELLULAR POOL OF CD45 ACCOMPANIES T-CELL ACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASES; LEUKOCYTE-COMMON ANTIGEN; INTEGRAL MEMBRANE-PROTEINS; RECEPTOR COMPLEX; MONOCLONAL-ANTIBODY; SIGNAL TRANSDUCTION; HUMAN-PLACENTA; ZETA-CHAIN; PHOSPHORYLATION; IDENTIFICATION AB The major tyrosine phosphatase activity against angiotensin detected in membranes of the antigen-specific T cell hybridoma 2B4 is contained in the cytoplasmic tail of the CD45 molecule. When these cells are stimulated with either an antibody directed against the T cell antigen receptor or an activating anti-Thy-1 antibody, there is a rapid redistribution of CD45 in the cells. The redistribution can be observed in two ways: morphology and subcellular fractionation. Morphologic examination of resting cells reveals intense CD45 staining of the Golgi as well as surface staining. Upon activation the Golgi is rapidly cleared of CD45. This redistribution is specific for CD45 and is not observed for an intrinsic Golgi protein, mannosidase II, or a protein traversing the secretory pathway, the T cell receptor. In activated cells, in contrast to resting cells, approximately 30% of the total cellular CD45 is precipitated either at 280 x g or at 200,000 x g through a 2.2 M sucrose cushion after cell homogenization. This fraction is not accessible to cell surface labeling. CD45 redistribution does not require hydrolysis of phosphatidylinositides and cannot be reproduced by the addition of phorbol ester and calcium ionophore. It does require the presence of an intact functional T cell receptor on the cell surface. These studies suggest that the residence time of CD45 within an intracellular organelle can be acutely regulated by a signal mediated via the T cell receptor. This regulation may control access of this phosphatase to critical substrates. RP MINAMI, Y (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 46 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 1991 VL 266 IS 14 BP 9222 EP 9230 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM038 UT WOS:A1991FM03800085 PM 1851171 ER PT J AU SHENKER, A GOLDSMITH, P UNSON, CG SPIEGEL, AM AF SHENKER, A GOLDSMITH, P UNSON, CG SPIEGEL, AM TI THE G-PROTEIN COUPLED TO THE THROMBOXANE-A2 RECEPTOR IN HUMAN PLATELETS IS A MEMBER OF THE NOVEL GQ FAMILY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING-PROTEIN; CARBOXYL-TERMINAL DECAPEPTIDE; HIGH-AFFINITY GTPASE; REGULATORY PROTEINS; PERTUSSIS-TOXIN; PHOSPHOLIPASE-C; ALPHA-SUBUNIT; ADENYLATE-CYCLASE; ANTIBODIES; MEMBRANES AB The thromboxane A2 (TXA2) receptor in human platelets is coupled to a pertussis toxin-insensitive G protein whose identity has remained unknown. Candidates for this role include the atypical G protein known as G(z) and members of a recently discovered G protein family known as G(q). Because of the proven utility of antibodies directed against the C terminus of G protein alpha-subunits as functional probes, we prepared an antibody against a synthetic decapeptide corresponding to the C-terminal sequence shared by alpha-11 and alpha-q, two members of the new family. This antibody (QL) does not recognize known alpha-subunits but selectively binds to a 42-kDa protein in a variety of tissues, including human platelet membranes. QL and two other C-terminal antibodies, QN and AS, known to recognize alpha-z and alpha-i2, respectively, were tested for their ability to block agonist-stimulated GTPase activity in human platelet membranes. Pretreatment of platelet membranes with AS has previously been shown to interfere with alpha-2 adrenergic receptor-mediated inhibition of adenylylcyclase. As expected, only AS antibody produced inhibition of alpha-2 receptor-stimulated GTPase. Pretreatment of membranes with QL, but not QN or AS, caused marked inhibition of TXA2 receptor-stimulated GTPase. This identifies the G protein coupled to human platelet TXA2 receptors as a member of the novel G(q) family. C1 ROCKEFELLER UNIV,DEPT BIOCHEM,NEW YORK,NY 10021. RP SHENKER, A (reprint author), NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,RM 8D17,BETHESDA,MD 20892, USA. NR 40 TC 352 Z9 353 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 1991 VL 266 IS 14 BP 9309 EP 9313 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM038 UT WOS:A1991FM03800097 PM 1851174 ER PT J AU GELLER, RL SMYTH, MJ STROBL, SL BACH, FH RUSCETTI, FW LONGO, DL OCHOA, AC AF GELLER, RL SMYTH, MJ STROBL, SL BACH, FH RUSCETTI, FW LONGO, DL OCHOA, AC TI GENERATION OF LYMPHOKINE-ACTIVATED KILLER ACTIVITY IN T-CELLS - POSSIBLE REGULATORY CIRCUITS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH FACTOR-BETA; TUMOR-INFILTRATING LYMPHOCYTES; PERIPHERAL-BLOOD LYMPHOCYTES; LAK CELLS; INTERLEUKIN-2; LYSIS; DIFFERENTIATION; IDENTIFICATION; PRECURSORS; EXPRESSION AB CD4+ and CD8+ T cells do not develop significant lymphokine-activated killer (LAK) activity when PBL are cultured with IL-2 or even when they are activated with a T cell stimulus such as OKT3 mAb. The possibility that a T cell regulatory mechanism prevents the development of LAK activity by CD4+ or CD8+ cells in OKT3 mAb and IL-2 cultures was tested by depleting CD8+ or CD4+ cells from PBL before stimulation with OKT3 and IL-2. Under these conditions, the remaining CD4+ and CD8+ cells were able to generate non-MHC-restricted lysis of NK-resistant tumor targets. Our data suggested that a regulatory signal was present in the culture to prevent the development of lytic function by T cells. T cells removed from the PBL cultures were, upon culture with IL-2, able to generate high LAK activity, suggesting that inhibition of the CD4+ or CD8+ T cell-mediated LAK activity was an active ongoing process, which blocked the lysis at the level of the activated cell and not the precursor cell. Mixing experiments demonstrated that the CD4+ or the CD8+ cells isolated from the PBL cultures were able to inhibit the development of lytic function in the CD4-depleted and CD8-depleted cultures. Transforming growth factor-beta (TGF-beta) has been shown to block LAK activity of NK cells in IL-2-stimulated cultures. When TGF-beta was added to CD4+- or CD8+-depleted cultures, it also inhibited LAK activity of T cells in a dose-dependent fashion, without interfering with T cell growth. Lytic activity returned to activated levels when TGF-beta was removed from the culture medium, thereby demonstrating the reversibility of TGF-beta inhibition. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,IMMUNOTHERAPY LAB,POB B,BLDG 560,FREDERICK,MD 21702. UNIV MINNESOTA,IMMUNOBIOL RES CTR,MINNEAPOLIS,MN 55455. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. RI Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU NCI NIH HHS [CA 47097, N01-CO-74102]; NIADDK NIH HHS [AM 13083] NR 32 TC 33 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1991 VL 146 IS 10 BP 3280 EP 3288 PG 9 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600003 PM 1673980 ER PT J AU SMYTH, MJ STROBL, SL YOUNG, HA ORTALDO, JR OCHOA, AC AF SMYTH, MJ STROBL, SL YOUNG, HA ORTALDO, JR OCHOA, AC TI REGULATION OF LYMPHOKINE-ACTIVATED KILLER ACTIVITY AND PORE-FORMING PROTEIN GENE-EXPRESSION IN HUMAN PERIPHERAL-BLOOD CD8+ LYMPHOCYTES-T - INHIBITION BY TRANSFORMING GROWTH-FACTOR-BETA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; SV40 LARGE-T; SERINE PROTEASE; NATURAL-KILLER; TGF-BETA-1 INHIBITION; CYTOKINE PRODUCTION; CELL-PROLIFERATION; MONONUCLEAR-CELLS; GAMMA-INTERFERON; PERFORIN GENE AB The effect of transforming growth factor-beta-1 (TGF-beta) on activation-induced CD8+ T cell cytotoxicity and gene expression was investigated. TGF-beta was demonstrated to inhibit pore-forming protein (PFP) mRNA expression and total benzoyloxycarbonyl-L-lysine thiobenzyl ester esterase activity in CD8+ T cells cultured with IL-2 and OKT3 mAb for 6 to 18 days. Consistently, in the absence or presence of TGF-beta, the PFP mRNA expression and lymphokine-activated killer (LAK) activity of CD8+ T cells were closely correlated. The inhibitory effects of TGF-beta on both CD8+ T cell PFP mRNA expression and LAK activity were reversible by removal of TGF-beta from the culture. Expression of lymphokines, adhesion/recognition molecules, and activated p55 IL-2R, previously implicated in the lytic mechanism of cytotoxic lymphocytes, either was not detectable or did not correlate with TGF-beta inhibition of LAK activity. In addition, independently of effector/target cell binding, the lectin- or heteroconjugated antibody-dependent cellular cytotoxicity of IL-2/OKT3 mAb-activated CD8+ T cells was inhibited by preculture with TGF-beta. TGF-beta also inhibited the rapid activation-induced expression of PFP mRNA and cytotoxic potential in resting T cells, thereby indicating that the effect of TGF-beta was independent of T cell proliferation. TGF-beta inhibition of CD8+ T cell PFP mRNA expression and cytotoxic potential was TGF-beta dose dependent; however, a variety of activation stimuli (including IL-2, IL-6, and OKT3 mAb) were all similarly inhibited by TGF-beta. Therefore, TGF-beta may be an important general regulator of CD8+ T cell cytotoxic function, in particular by suppressing expression of PFP, a major cytolytic protein implicated in the lytic function of cytotoxic lymphocytes. RP SMYTH, MJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA. RI Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU NCI NIH HHS [N01-CO-74102] NR 57 TC 134 Z9 141 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1991 VL 146 IS 10 BP 3289 EP 3297 PG 9 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600004 PM 1827481 ER PT J AU TANG, AM UDEY, MC AF TANG, AM UDEY, MC TI INHIBITION OF EPIDERMAL LANGERHANS CELL-FUNCTION BY LOW-DOSE ULTRAVIOLET-B RADIATION - ULTRAVIOLET-B RADIATION SELECTIVELY MODULATES ICAM-1 (CD54) EXPRESSION BY MURINE LANGERHANS CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; ANTIGEN-PRESENTING CAPACITY; DENDRITIC CELLS; CONTACT HYPERSENSITIVITY; T-CELLS; ALLOANTIGEN PRESENTATION; MONOCLONAL-ANTIBODIES; UV IRRADIATION; LYMPHOCYTES-T; INVITRO AB Immunosuppressive effects of low levels of ultraviolet B (UVB) radiation on cutaneous immune responses have been attributed to deleterious effects of UVB radiation on epidermal Langerhans cells (LC). To determine how UVB radiation modulates LC function we examined the effect of in vitro UVB exposure on LC accessory cell activity and surface phenotype. Exposure of BALB/c murine epidermal cells to low dose (less-than-or-equal-to 200 J/m2) UVB radiation in vitro inhibited their ability to support the mitogenic response of unstimulated, accessory cell-depleted splenic T cells to anti-CD3 mAb. LC accessory cell activity was also inhibited when LC were exposed to UVB radiation in situ, although several-fold higher doses of UVB radiation were required to achieve complete inhibition of LC function. This dose-dependent inhibition was mediated through a direct effect on LC that could not be reversed by IL-1 or IL-6 alone or in combination, or granulocyte-macrophage-CSF. TNF-alpha did not inhibit LC accessory cell function in this assay and anti-TNF-alpha neutralizing antibodies did not reverse the inhibitory effects of UVB radiation. UVB irradiated LC failed to participate in the anti-CD3-dependent clustering that normally occurs between T cells and LC during the proliferative response of murine T cells to anti-CD3 mAb, suggesting that UV radiation may interfere with accessory cell function by preventing intercellular adhesion. Two-color flow cytometric studies revealed low levels of the ICAM-1 on freshly isolated LC and some keratinocytes. ICAM-1 expression on LC increased 15 to 20-fold within the first 24 h in vitro and continued to increase during a 72-h culture period. The integrin LFA-1 was not identified on freshly isolated or cultured LC but was detected on responding T cells. Prior exposure of LC to UVB radiation (50 or 100 J/m2) inhibited the increase in ICAM-1 expression that normally occurs in vitro by up to 70% whereas surface levels of class II MHC Ag, CD45 and Fc-gamma-receptors were not affected. Blocking studies revealed that anti-CD3 induced T cell proliferation and T cell-LC cluster formation was inhibited by both anti-LFA-1 and anti-ICAM-1 mAb suggesting that ICAM-1 expressed on LC must bind to LFA-1 on T cells to facilitate proliferative responses of T cells to anti-CD3 mAb. We conclude that the in vitro inhibitory effects of low dose UVB radiation on LC accessory function may result because UVB radiation prevents upregulation of ICAM-1 expression by LC in culture. Local immunosuppressive effects of UVB radiation on cutaneous immune responses may reflect similar selective effects of UVB radiation on the expression of ICAM-1 by LC in vivo. C1 NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N254,BETHESDA,MD 20892. NR 41 TC 140 Z9 143 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1991 VL 146 IS 10 BP 3347 EP 3355 PG 9 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600011 PM 1673983 ER PT J AU YOUNG, KR AMBRUS, JL MALBRAN, A FAUCI, AS TENNER, AJ AF YOUNG, KR AMBRUS, JL MALBRAN, A FAUCI, AS TENNER, AJ TI COMPLEMENT SUBCOMPONENT CLQ STIMULATES IG PRODUCTION BY HUMAN LYMPHOCYTES-B SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL DIFFERENTIATION FACTOR; ANAPHYLATOXIN-MEDIATED REGULATION; SYSTEMIC LUPUS-ERYTHEMATOSUS; PIG PERITONEAL-MACROPHAGES; HUMAN PERIPHERAL-BLOOD; IMMUNE-RESPONSE; HUMAN-MONOCYTES; DEFICIENCY STATES; 1ST COMPONENT; GROWTH-FACTOR AB The regulation of Ig production by human B lymphocytes is a complex process involving interactions among B cells, APC, T lymphocytes and soluble factors including activation, growth, and differentiation factors. Components of the complement system, including C3a, C3b, C3d, and C5a, have been shown to influence various stages in this process. In this study, we demonstrate that the C1q subcomponent of complement binds to both small resting and large activated B cells and stimulates immunoglobulin production by Staphylococcus aureus Cowan-activated tonsillar B lymphocytes. This effect is present whether C1q is added to the B cells either at the beginning or near the end of a 7-day culture period and is not associated with enhancement of proliferation. The C1q stimulation of Ig production is, however, associated with increased steady state levels of mRNA for the mu-Ig H chain. Furthermore, C1q stimulated IgM production by the human B cell line SKW 6.4, which is capable of secreting IgM in response to B cell differentiation factors (BCDF). SLE is a disorder frequently associated with polyclonal activation of B lymphocytes. We studied the effect of C1q on B cells from two patients with this disorder and one with an SLE-like illness, all selected for the predominance of either IgM or IgG in serum. Spontaneous or BCDF-stimulated Ig secretion was of the isotype predominant in vivo, whereas C1q selectively stimulated B cells to produce the other isotype (IgG vs IgM). Thus, C1q interacts with B lymphocytes in a manner distinct from that of BCDF found in mixed lymphocyte supernatants. C1q may be an important factor influencing the production of Ig by B lymphocytes in normal individuals and in patients with abnormalities of B cell activity. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. AMER RED CROSS,ROCKVILLE,MD 20855. NR 74 TC 52 Z9 52 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1991 VL 146 IS 10 BP 3356 EP 3364 PG 9 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600012 PM 1902854 ER PT J AU KALTER, DC GREENHOUSE, JJ ORENSTEIN, JM SCHNITTMAN, SM GENDELMAN, HE MELTZER, MS AF KALTER, DC GREENHOUSE, JJ ORENSTEIN, JM SCHNITTMAN, SM GENDELMAN, HE MELTZER, MS TI EPIDERMAL LANGERHANS CELLS ARE NOT PRINCIPAL RESERVOIRS OF VIRUS IN HIV DISEASE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HTLV-III/LAV INFECTION; T-CELL; LYMPHOCYTES-T; LYMPH-NODES; MONONUCLEAR PHAGOCYTES; INSITU HYBRIDIZATION; PERIPHERAL-BLOOD; PRIMARY TARGET; III INFECTION AB Several reports implicate Langerhans cells of skin as susceptible targets, reservoirs, and vectors for transmission of HIV: 1) numbers of Langerhans cells in skin of HIV-infected patients were decreased about 50% of that in control skin; 2) as many as 30% of Langerhans cells in the skin of HIV-infected patients were morphologically abnormal; 3) viral particles typical for HIV were identified in or around 2 to 5% of these cells; and 4) infectious HIV was isolated from skin biopsies of infected patients. These results were consistent with similar observations of HIV-infected macrophages in such tissues as brain, lung, and lymph node. Despite these findings, other investigators find no evidence for virus infection in the epidermis of HIV-infected patients by any of several immunohistochemical or ultrastructural criteria. To address this controversy, we obtained skin from 28 HIV-seropositive subjects at various clinical stages by full thickness biopsy or suction blister. Samples were analyzed by transmission electron microscopy for presence of HIV virions, by immunofluorescent staining for viral proteins, by in situ hybridization for HIV-specific mRNA, by polymerase chain reaction amplification of virus-specific DNA, and by direct virus isolation by coculture of epidermis onto monocyte target cells. By any of these techniques, demonstration of HIV in the epidermis of infected patients was equivocal and even then, infrequent. In contrast, viral DNA was detected from the dermis of the same skin samples (26 of 28 samples). Moreover, the number and morphology of Langerhans cells in skin of infected patients were within normal limits, regardless of stage of disease. These studies in toto suggest that a role for Langerhans cells as a principal viral reservoir or vector of transmission is highly unlikely. C1 HENRY M JACKSON FDN,ROCKVILLE,MD 20850. WALTER REED ARMY MED CTR,DIV COMMUNICABLE DIS & IMMUNOL,DEPT CELLULAR IMMUNOL,ROCKVILLE,MD 20850. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20007. NR 57 TC 56 Z9 56 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1991 VL 146 IS 10 BP 3396 EP 3404 PG 9 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600017 PM 2026871 ER PT J AU RIECKMANN, P DALESSANDRO, F NORDAN, RP FAUCI, AS KEHRL, JH AF RIECKMANN, P DALESSANDRO, F NORDAN, RP FAUCI, AS KEHRL, JH TI IL-6 AND TUMOR-NECROSIS-FACTOR-ALPHA - AUTOCRINE AND PARACRINE CYTOKINES INVOLVED IN B-CELL FUNCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; NF-KAPPA-B; STIMULATORY FACTOR-II; SYSTEMIC LUPUS-ERYTHEMATOSUS; INTERLEUKIN-6 GENE; NUCLEAR FACTOR; TRANSCRIPTION FACTOR; LYMPHOCYTES-B; T-CELLS; DIFFERENTIATION AB IL-6 and TNF-alpha are synthesized and secreted by normal tonsillar B cells after stimulation with the polyclonal B cell activator Staphylococcus aureus Cowan strain 1 (SAC) and IL-2 as well as spontaneously by in vivo activated B cells from patients with hypergammaglobulinemia. Using specific neutralizing antibodies, both factors were shown to be involved in autocrine and/or paracrine regulation of B cell differentiation. IgG induced by SAC/IL-2 stimulation was reduced 73% with an anti-IL-6 antibody and 40% with an anti-TNF-alpha antibody. Similar effects of these antibodies were observed on the spontaneous in vitro IgG production by lymphoblastic B cells from six patients with hypergammaglobulinemia. Kinetic studies with SAC/IL-2-activated B cells revealed that the anti-TNF-alpha antibody must be present at the beginning of the culture to exert an effect on Ig production, whereas the anti-IL-6 antibody reduced Ig production even if added as late as day 3. This sequential action of TNF-alpha and IL-6 on B cell differentiation was reflected by different kinetics of release of these two cytokines into the supernatant of SAC/IL-2 activated B cells; TNF-alpha peaked at 24 h and IL-6 at 96 h after stimulation. In addition, it was shown that IL-6 production by in vitro-activated B cells was partially blocked by an anti-TNF-alpha antibody suggesting that TNF-alpha regulates IL-6 production in normal B cells via an autocrine pathway. We also investigated the effects of TGF-beta on TNF-alpha and IL-6 production by normal B cells. Although TGF-beta inhibited Ig production by in vitro-activated and in vivo-activated B cells, it did not inhibit the release of these cytokines from normal B cells. Furthermore, TGF-beta did not inhibit the induction of nuclear factor-IL-6 nor the expression of IL-6R on activated B cells. Thus, although the biologic effects of anti-IL-6 and TGF-beta on B cell Ig production are similar, their mechanisms of actions appear to be distinct. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B13,BETHESDA,MD 20892. NCI,MED BRANCH,NATL DIV CANC TREATMENT,BETHESDA,MD 20892. NR 40 TC 95 Z9 96 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1991 VL 146 IS 10 BP 3462 EP 3468 PG 7 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600027 PM 2026875 ER PT J AU YOSHIMURA, T YUHKI, N AF YOSHIMURA, T YUHKI, N TI NEUTROPHIL ATTRACTANT ACTIVATION PROTEIN-1 AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN RABBIT - CDNA CLONING AND THEIR EXPRESSION IN SPLEEN-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BLOOD MONONUCLEAR LEUKOCYTES; CHEMOTACTIC FACTOR MDNCF; AMINO-ACID-SEQUENCE; GENE JE; PURIFICATION; PEPTIDE; INVIVO; SKIN; INTERLEUKIN-1; SIMILARITY AB Rabbit neutrophil attractant/activation protein-1 (NAP-1) and monocyte chemoattractant protein-1 (MCP-1) were investigated. Rabbit spleen cells stimulated with 5-mu-g/ml of Con A produced both neutrophil and monocyte chemotactic activity. Physicochemical characteristics of those activities obtained by HPLC gel filtration and HPLC chromatofocusing were very similar to those of human NAP-1 and MCP-1, suggesting that rabbit spleen cells produce NAP-1 and MCP-1 after Con A stimulation. A cDNA library was constructed from mRNA purified from Con A-stimulated rabbit spleen cells and screened with oligonucleotide probes. By two rounds of screening, NAP-1 and MCP-1 cDNA were cloned. NAP-1 cDNA comprises 1500 bp with an open reading frame that encodes for a 101-amino acid protein highly similar to human NAP-1. MCP-1 cDNA comprises 607 bp with an open reading frame that encodes for a 124-amino acid protein highly similar to human MCP-1. Expression of NAP-1 and MCP-1 mRNA by rabbit spleen cells was studied. Both Con A- and LPS-stimulated spleen cells expressed NAP-1 and MCP-1 mRNA, but the kinetics of expression were different. Con A rapidly induced high NAP-1 and MCP-1 mRNA expression. LPS also rapidly induced NAP-1 mRNA expression, but high MCP-1 mRNA expression was not observed until 15 h after stimulation. Immunoprecipitation of metabolically labeled NAP-1 and MCP-1 with anti-human NAP-1 or MCP-1 polyclonal antibodies was attempted. Immunoprecipitated rabbit NAP-1 with a molecular mass of about 7 kDa was detected by SDS-PAGE and radioautography, but MCP-1 was not. Cloned rabbit NAP-1 and MCP-1 will give us opportunities to study the role of NAP-1 and MCP-1 in vivo. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,GENET SECT,FREDERICK,MD 21702. RP YOSHIMURA, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,BLDG 560,ROOM 12-71,FREDERICK,MD 21702, USA. NR 34 TC 76 Z9 80 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1991 VL 146 IS 10 BP 3483 EP 3488 PG 6 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600030 PM 2026877 ER PT J AU WINTER, CC CARRENO, BM TURNER, RV KOENIG, S BIDDISON, WE AF WINTER, CC CARRENO, BM TURNER, RV KOENIG, S BIDDISON, WE TI THE 45-POCKET OF HLA-A2.1 PLAYS A ROLE IN PRESENTATION OF INFLUENZA-VIRUS MATRIX PEPTIDE AND ALLOANTIGENS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; CELL RECOGNITION; SIDE-CHAINS; ANTIGEN; BINDING; SPECIFICITY; INHIBITION; PROTEINS; RECEPTOR; COMPLEX AB Amino acid substitutions were introduced into the 45 pocket of HLA-A2.1 to determine the potential role of this structurally defined feature of class I molecules in viral peptide and alloantigen presentation. The 45 pocket lies below the alpha-1-domain alpha-helix and is composed of five amino acids, three of which differ between HLA-A2.1 and HLA-B37. These two class I molecules have previously been shown to have largely non-overlapping peptide-binding specificities. Site-directed mutagenesis was used to replace the hydrophobic residues at positions 24, 45, and 67 in the 45 pocket of HLA-A2.1 with the hydrophilic amino acids found in these positions in HLA-B37. Thus, three single amino acid mutants were produced: 24A --> S, 45 M --> T, and 67V --> S. These mutants were transfected into HMy2.C1R cells and assessed for their ability to present influenza virus matrix M1 57-68 peptide and HTLV-I Tax-1 2-25 peptide to HLA-A2.1-restricted, peptide-specific CTL and to present alloantigens to HLA-A2-allospecific CTL lines. Each of these substitutions in the 45 pocket produced a molecule that failed to present the M1 peptide to most M1 peptide-specific CTL lines. In contrast, none of these mutations affected presentation of the Tax-1 peptide to Tax-1-specific CTL lines, which indicates that these mutant HLA-A2 molecules can function in viral peptide presentation. Two of the three substitutions in the 45 pocket resulted in lack of recognition by a subset of HLA-A2 allospecific CTL lines. These results demonstrate that the amino acid side chains in the 45 pocket can strongly influence peptide presentation and suggest that the 45 pocket may play a role in determining peptide-binding specificity. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP WINTER, CC (reprint author), NINCDS,NEUROIMMUNOL BRANCH,MOLEC IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 20 TC 43 Z9 43 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 MAY 15 PY 1991 VL 146 IS 10 BP 3508 EP 3512 PG 5 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600034 PM 2026879 ER PT J AU MCINTYRE, TM HOLMES, KL STEINBERG, AD KASTNER, DL AF MCINTYRE, TM HOLMES, KL STEINBERG, AD KASTNER, DL TI CD5+ PERITONEAL B-CELLS EXPRESS HIGH-LEVELS OF MEMBRANE, BUT NOT SECRETORY, C-MU MESSENGER-RNA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INSITU HYBRIDIZATION; LYMPHOCYTE-B; NORMAL MICE; AUTOIMMUNE; DIFFERENTIATION; LINEAGE; CHAIN AB We used in situ hybridization to study Ig mRNA levels in murine peritoneal and splenic B cells. Ig mRNA production fell into three distinct groups: low, intermediate, and high. Splenic B cells primarily exhibited low levels characteristic of resting B cells or high Ig mRNA levels characteristic of plasma cells. In contrast, a significant fraction of peritoneal B cells exhibited intermediate Ig mRNA levels. Intermediate Ig mRNA was T cell dependent in that congenic nu/nu mice had far fewer peritoneal cells expressing the intermediate Ig message than their wild type counterparts. CD5+ CD11b+ IgM(bright+) peritoneal B cells were found to be mainly responsible for the production of intermediate Ig mRNA levels. The peritoneal CD5- CD11b+ IgM(bright+) "sister" B cell subpopulation contained a lower percentage of intermediate Ig mRNA-producing B cells. CD5- CD11b- IgM(dull+) "conventional" B cells produced negligible levels of Ig mRNA, comparable to those of unfractionated splenic B cells. Northern analysis showed that the majority of Ig mRNA expressed in the peritoneum is of the membrane rather than the secreted form. Consistent with that result, in short-term culture, peritoneal cells showed markedly less Ig secretion than did spleen cells. These studies describe novel Ig mRNA expression by peritoneal B cells and emphasize that within the peritoneal cavity, B cells do not tend to become antibody-secreting cells. C1 NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. RP MCINTYRE, TM (reprint author), NIAMSD,ARTHRIT BRANCH,CELLULAR IMMUNOL SECT,BLDG 10,ROOM 9N-228,BETHESDA,MD 20892, USA. NR 23 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1991 VL 146 IS 10 BP 3639 EP 3645 PG 7 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600052 PM 1709199 ER PT J AU SCHWARTZENTRUBER, DJ TOPALIAN, SL MANCINI, M ROSENBERG, SA AF SCHWARTZENTRUBER, DJ TOPALIAN, SL MANCINI, M ROSENBERG, SA TI SPECIFIC RELEASE OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, TUMOR-NECROSIS-FACTOR-ALPHA, AND IFN-GAMMA BY HUMAN TUMOR-INFILTRATING LYMPHOCYTES AFTER AUTOLOGOUS TUMOR-STIMULATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECOMBINANT INTERFERON-GAMMA; T-CELL CLONES; PHASE-I TRIAL; CANCER-PATIENTS; INTERLEUKIN-2 PRODUCTION; MONOCLONAL-ANTIBODY; SURFACE-ANTIGENS; GENE-EXPRESSION; MELANOMA-CELLS; HLA-DR AB Tumor-infiltrating lymphocytes (TIL) have been cultured from a variety of human tumors, and some melanoma TIL have demonstrated specific, MHC-restricted recognition of autologous tumor in short term lysis assays. The current study investigates cytokine release by TIL as an indicator of specific tumor recognition. We have identified two of four melanoma and one of seven breast carcinoma TIL cultures that specifically release granulocyte-macrophage-CSF, TNF-alpha, and IFN-gamma after autologous tumor stimulation. The other cultures either do not secrete cytokine or secrete cytokine in a nonspecific fashion. The amount of specific cytokine released is directly related to the number of TIL and stimulating tumor cells. Studies of TIL, from two melanoma patients, separated into CD4+ and CD8+ populations revealed that CD8+ cells were responsible for virtually all of the specific cytokine secretion, although both populations released cytokines when activated by immobilized anti-CD3 antibody. Specific cytokine release by CD8+ TIL was inhibited by anti-MHC class I mAb. Specific cytokine release was also detected from a CD4+ breast cancer TIL culture, and this was inhibited by anti-MHC class II mAb. The clinical significance of this specific mode of immune antitumor reactivity is currently under investigation. RP SCHWARTZENTRUBER, DJ (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,9000 ROCKVILLE PIKE BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 40 TC 129 Z9 130 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1991 VL 146 IS 10 BP 3674 EP 3681 PG 8 WC Immunology SC Immunology GA FL836 UT WOS:A1991FL83600057 PM 1902860 ER PT J AU CAO, CJ LOCKWICH, T SCOTT, TL BLUMENTHAL, R SHAMOO, AE AF CAO, CJ LOCKWICH, T SCOTT, TL BLUMENTHAL, R SHAMOO, AE TI UNCOUPLING OF CA2+ TRANSPORT FROM ATP HYDROLYSIS ACTIVITY OF SARCOPLASMIC-RETICULUM (CA2+ + MG2+)-ATPASE SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE SARCOPLASMIC RETICULUM; CA2+-PUMP; TRANSPORT; HYDROLYSIS; TRYPSIN DIGESTION; UNCOUPLING ID ADENOSINE-TRIPHOSPHATASE; CALCIUM-PUMP; CA-2+,MG-2+-ADENOSINE TRIPHOSPHATASE; MG-2+-ADENOSINE TRIPHOSPHATASE; CHEMICAL MODIFICATION; TRYPTIC DIGESTION; CROSS-LINKING; CA-2+; CA2+-ATPASE; BINDING AB In reconstituted rabbit skeletal muscle (Ca2+ + Mg2+)-ATPase proteoliposomes, Ca2+-uptake is decreased by more than 90% with T2 cleavage (Arg-198). However, no difference in the ATP dependence of hydrolysis activity is seen between SR and trypsin-treated SR. A large decrease in E-P formation and hydrolysis activity of the enzyme appear only at T3 cleavage, which represents the cleavage of A1 fragment to A1a + A1b forms. The disappearance of hydrolysis activity due to digestion is prior to the disappearance of E-P formation. No significant difference is found in the passive Ca2+ efflux between control SR and tryptically digested SR in the absence of Mg2+ + ruthenium red or in the presence of ATP. However, the passive Ca2+ efflux rate for tryptically digested SR is much larger than control SR in the presence of Mg2+ + ruthenium red. These results show that the Ca2+ channel cannot be closed after trypsin digestion of SR membranes by the presence of the Ca2+ channel inhibitors, Mg2+ and ruthenium red. In the reconstituted ATPase proteoliposomes, the Ca2+ efflux rates are the same regardless of digestion (T2); also, efflux is not affected by the presence or absence of Mg2+ + ruthenium red. These results indicate that T2 cleavage causes 'uncoupling' of the 'Ca2+-pump' from ATP hydrolytic activity. A theoretical model is developed in order to fit the extent of tryptic digestion of the A fragment of the (Ca2+ + Mg2+)-ATPase polypeptide with the loss of Ca2+-transport. Fits of the theoretical equations to the data are consistent with that Ca2+-transport system appears to require a dimer of the polypeptide (Ca2+ + Mg2+)-ATPase. C1 BOSTON BIOMED RES INST,DEPT MUSCLE RES,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. NIH,FUNCT LAB THEORET BIOL,BETHESDA,MD 20892. NIH,MEMBRANE STRUCT SECT,BETHESDA,MD 20892. RP CAO, CJ (reprint author), SCH MED BALTIMORE,DEPT BIOL CHEM,MEMBRANE BIOCHEM RES LAB,660 W REDWOOD ST,BALTIMORE,MD 21201, USA. FU NIGMS NIH HHS [GM 32247] NR 62 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY 15 PY 1991 VL 103 IS 2 BP 97 EP 111 PG 15 WC Cell Biology SC Cell Biology GA FN897 UT WOS:A1991FN89700001 PM 1649382 ER PT J AU ARAUJO, M HAVLIN, S WEISS, GH STANLEY, HE AF ARAUJO, M HAVLIN, S WEISS, GH STANLEY, HE TI DIFFUSION OF WALKERS WITH PERSISTENT VELOCITIES SO PHYSICAL REVIEW A LA English DT Article ID ANOMALOUS DIFFUSION; ENHANCED DIFFUSION; DISORDERED MEDIA; TRANSPORT; TIME; FIELDS; SUPERDIFFUSION AB We describe some properties for a phenomenological model of superdiffusion based on a generalization of the persistent random walk in one dimension to continuous time. The time spent moving to either increasing or decreasing x is characterized by a fractal-time pausing time density, psi(t) approximately T-alpha/t-alpha + 1, with 1 < alpha < 2. For this system it is shown that asymptotically p(0,t) approximately 1/t1/alpha. The form of the profile is shown to be Gaussian near the peak and to fall off like tx-(1 + alpha) near the tails, and the survival probability is asymptotically proportional to exp(- Bt/L-alpha). These results are confirmed by numerical calculations based on the method of exact enumeration. C1 BOSTON UNIV, DEPT PHYS, BOSTON, MA 02215 USA. NIH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. RP BOSTON UNIV, CTR POLYMER STUDIES, BOSTON, MA 02215 USA. NR 28 TC 35 Z9 35 U1 0 U2 2 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2469-9926 EI 2469-9934 J9 PHYS REV A JI Phys. Rev. A PD MAY 15 PY 1991 VL 43 IS 10 BP 5207 EP 5213 DI 10.1103/PhysRevA.43.5207 PG 7 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA FN053 UT WOS:A1991FN05300002 ER PT J AU HAVLIN, S KOPELMAN, R SCHOONOVER, R WEISS, GH AF HAVLIN, S KOPELMAN, R SCHOONOVER, R WEISS, GH TI DIFFUSIVE MOTION IN A FRACTAL MEDIUM IN THE PRESENCE OF A TRAP SO PHYSICAL REVIEW A LA English DT Article ID NEAREST-NEIGHBOR DISTANCES; RATE LAWS; PARTICLE DISTRIBUTIONS; STATISTICAL PROPERTIES; ONE DIMENSION; KINETICS; MIGRATION; DENSITY; MODEL AB There have been many studies of transport in an unbounded fractal medium. Here we discuss a number of quantities related to the concentration of reactants diffusing in fractal media in the presence of a trapping point. This investigation is suggested by an extension of the Smoluchowski model to calculate reaction rates in such media [M. von Smoluchowski, Phys. Z. 16, 321 (1915); 17, 557 (1917); 17, 585 (1917)]. Results, some analytic and some based on a scaling argument, are given for the flux into the trap, which is the analog of the reaction rate, in addition to the concentration profile in the neighborhood of the trap and the time dependence of the distance between the trap and the nearest untrapped particle. The results of our theory are found to be in good agreement with Monte Carlo and exact enumeration calculations for the concentration profile on a Sierpinski gasket and on an infinite percolation cluster at criticality. Some scaling and numerical results are reported for the situation in which the traps move in the presence of fixed particles. C1 BAR ILAN UNIV, DEPT PHYS, IL-52100 RAMAT GAN, ISRAEL. UNIV MICHIGAN, ANN ARBOR, MI 48109 USA. RP NIH, BETHESDA, MD 20892 USA. NR 31 TC 22 Z9 22 U1 0 U2 1 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 2469-9926 EI 2469-9934 J9 PHYS REV A JI Phys. Rev. A PD MAY 15 PY 1991 VL 43 IS 10 BP 5228 EP 5232 DI 10.1103/PhysRevA.43.5228 PG 5 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA FN053 UT WOS:A1991FN05300005 ER PT J AU LEWALLE, JM CASTRONOVO, V GOFFINET, G FOIDART, JM AF LEWALLE, JM CASTRONOVO, V GOFFINET, G FOIDART, JM TI MALIGNANT-CELL ATTACHMENT TO ENDOTHELIUM OF EXVIVO PERFUSED HUMAN UMBILICAL VEIN - MODULATION BY PLATELETS, PLASMA AND FIBRONECTIN SO THROMBOSIS RESEARCH LA English DT Article DE MALIGNANT CELL; ENDOTHELIAL CELLS; VEIN PERFUSION; PLATELET; FIBRONECTIN ID EXTRACELLULAR-MATRIX; CANCER METASTASIS; LUNG COLONIZATION; TUMOR-CELLS; FIBROBLASTS; INVASION; ADHESION; AGGREGATION; CARCINOMA; LODGEMENT AB The success of blood-born metastatic spread depends upon a key event: the tumor cell arrest and attachment to the host organ vasculature. In the present study, we have investigated interactions between several normal and cancer cell lines and vascular endothelium in a model of ex vivo perfusion of human umbilical vein. In this system, hydrodynamic parameters are monitored and endothelial cells are kept in their original environment known to modulate their phenotype. Metastatic tumor cell adhesion to the perfused endothelium was found to be significantly higher than that of normal cells tested. Platelets and soluble plasma factors including fibronectin promoted tumor cell arrest and adhesion to endothelium. Altogether our results indicate that the ex vivo perfusion of human umbilical vein allows the study of the interactions between malignant tumor cells, circulating plasma or blood cells and the endothelium during blood-born metastatic spread. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. STATE UNIV LIEGE,DEPT ZOOL,B-4000 LIEGE,BELGIUM. RP LEWALLE, JM (reprint author), STATE UNIV LIEGE,BIOL LAB,B-4000 LIEGE,BELGIUM. NR 35 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD MAY 15 PY 1991 VL 62 IS 4 BP 287 EP 298 DI 10.1016/0049-3848(91)90149-Q PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA FL348 UT WOS:A1991FL34800006 PM 1866711 ER PT J AU RAO, JKM ERICKSON, JW WLODAWER, A AF RAO, JKM ERICKSON, JW WLODAWER, A TI STRUCTURAL AND EVOLUTIONARY RELATIONSHIPS BETWEEN RETROVIRAL AND EUKARYOTIC ASPARTIC PROTEINASES SO BIOCHEMISTRY LA English DT Article ID SYNTHETIC HIV-1 PROTEASE; X-RAY ANALYSES; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; 2.3-A RESOLUTION; 1.8-A RESOLUTION; PORCINE PEPSIN; ACID PROTEASES; SEQUENCE; REFINEMENT AB Three-dimensional crystal structures of the homologous retroviral proteinases from Rous sarcoma virus (RSV PR) and from human immunodeficiency virus (HIV-1 PR) are to a large extent similar and bear close resemblance to the six known structures of the bilobal fungal and mammalian aspartic proteinases. Systematic three-dimensional structural superpositions were carried out between the retroviral and the eucaryotic aspartic proteinases. Both retroviral enzymes were found to be similarly related to their fungal and mammalian counterparts. The most strongly conserved parts correspond to those regions in the N- and C-domains of the eucaryotic enzymes that are related by the interdomain dyad and consist of a combination of secondary structural elements that form the psi-loop-alpha helix motif at the active sites of the aspartic proteinases. The retroviral proteinase monomer exhibits nearly the same degree of structural equivalence to the N- and C-domains of the eucaryotic enzymes. In light of the deduced structural relationships between HIV-1 PR and RSV PR, sequence alignments were performed for a number of retroviral proteinases from different subfamilies. There are three highly conserved amino acid sequence stretches,of which two belong to the psi-loop-alpha helix motif, that bear moderate sequence similarity with the eucaryotic enzymes. The third conserved sequence stretch among the retroviral proteinases belongs to the flap and bears no resemblance to the flap sequences in the eucaryotic enzymes. The interdomain antiparallel beta-sheet in the cellular enzymes differs from the intersubunit beta-sheet in the number, arrangement, and directionality of strands, suggesting the possibility of convergent evolution. However, a more detailed topological analysis of the two sheets revealed that they indeed have a direct structural relationship. This represents an unusual evolutionary example of how a combination of strand deletion and strand interchange events can combine to preserve the functionality of a critical secondary structural element. Overall, the structural comparisons argue strongly for the evolutionary relatedness of the eucaryotic and retroviral aspartic proteinases to a common ancestral domain or subunit. Since no aspartic proteinase motif has yet been discovered in procaryotes, we speculate that the retroviral enzyme evolved from a cellular gene by one or more deletion events, similar to the case for certain viral oncogenes that are deletion products of cellular protooncogenes. C1 ABBOTT LABS,PROT CYRSTALLOG LAB,ABBOTT LABS,IL 60064. RP RAO, JKM (reprint author), ADV BIOSCI LABS INC,NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,MACROMOLEC STRUCT LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [U01 AI27220-01] NR 38 TC 82 Z9 82 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 14 PY 1991 VL 30 IS 19 BP 4663 EP 4671 DI 10.1021/bi00233a005 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FL550 UT WOS:A1991FL55000005 PM 1851433 ER PT J AU MIHALYI, E TERCERO, JC DIAZMAURINO, T AF MIHALYI, E TERCERO, JC DIAZMAURINO, T TI CLOTTING OF FIBRINOGEN .5. CHANGES IN PH ASSOCIATED WITH CLOTTING OF FIBRINOGEN - KINETIC-STUDIES OF THE PH SHIFT AND CORRELATION OF THE PH CHANGE WITH THE RELEASE OF FIBRINOPEPTIDES AND THE ENSUING POLYMERIZATION SO BIOCHEMISTRY LA English DT Article ID THROMBIN; CALCIUM AB The effect of the initial pH and the concentrations of thrombin, fibrinogen, and Ca2+ upon the rate of pH change associated with clotting of bovine fibrinogen by human thrombin was investigated at pH 6.80, 7.80, and 8.80, 0.3 ionic strength, 25-degrees-C, and 19.5 mg/mL final fibrinogen concentration. At pH 6.80 and 7.80, the reaction was first order, with rate constant k1. At pH 8.80, a first-order reaction of the release of H+ (k1) was followed by a partial rebinding of these in a reaction consecutive to the first one (k2). At each of the above pH values, k1 was proportional to thrombin concentration in the 0.05-3.0 min-1 range investigated. The k1 constants were 0.111+/- 0.001, 0.250 +/- 0.005, and 0.190 +/- 0.002 min-1 (NIH thrombin units)-1 mL-1 at pH 6.80, 7.80, and 8.80, respectively. Plots of log rate vs log thrombin concentration of these data were linear with slopes close to 1 at all three pH values. The rate of the second reaction (k2) was independent of both the thrombin and the initial fibrinogen concentration. The pH dependence of k1 exhibited a bell-shaped curve that could be resolved into the effect of one group with a pK of 7.27 that increased the rate and another with a pK of 9.22 that decreased the rate. With constant thrombin concentration but varying fibrinogen concentration, plots of 1/k1 vs [fibrinogen] were linear, but the lines did not pass through the origin. From the slope and intercept, k(cat) and K(M) of the Michaelis-Menten equation could be calculated. The same parameters were obtained also from initial velocity vs [fibrinogen] plots. Values of k(cat) were consistent and accurate; those of K(M) were more scattered. K(M) was (22.4-34.2) X 10(-6) M at pH 6.80 and approximately 7 X 10(-6) M in the pH 7.26-8.80 range. The latter value, pertaining to the release of H+ ions, is in agreement with values in the literature for K(M) of the release of fibinopeptide A by thrombin in the 7.4-8.0 pH range. The value of k(cat) s-1 (unit of thrombin)-1 mL-1 increases from 1.2 X 10(-10) s-1 unit of thrombin-1 mL-1 at pH 6.80 to 2.46 X 10(-10) at pH 7.80 and then decreases to 2.01 X 10(-10) 10(-1) (units of thrombin)-1 mL-1 at pH 8.80. The k(cat) values are significantly lower than those in the literature for the release of fibrinopeptide A. The difference may be caused by the higher ionic strength (0.3 vs 0.15). The amounts of H+ liberated were 3.0, 1.9, and 3.0 equiv of H+ mol of fibrinogen at the respective pH values. The pH shift was correlated with the release of fibrinopeptides and with polymerization, the latter monitored by the increase of turbidity. Release of fibrinopeptide A followed first-order kinetics; release of fibrinopeptide B followed a first-order reaction consecutive to release of fibrinopeptide A. At pH 6.80, the pH shift lagged behind the release of FPA, by a factor of 0.6. Most of the H+ at this pH originates in the polymerization or changes following this. Therefore, the delay must occur in this phase. At pH 7.80, pH shift and release of FPA are simultaneous. There is no indication of contribution from release of FPB to the pH shift. The stoichiometry of H+ released also supports this contention. The most likely explanation of this finding is an increase by the polymerization reaction of the pK of the alpha-NH2 groups formed by release of FPB. At pH 8. 80, the pH shift again lags behind release of FPB; however, the reaction curve can be reconstructed accurately by assuming that FPA contributes fully, while FPB to about half the extent, to the pH shift. This places the pK of the groups produced by release of the latter to approximately 8.8. At all three pH values, the turbidity curves coincided or were slightly ahead of the FPA release curves, showing that the latter have a determining role in polymerization and FPB is not directly involved. The pH shift and release of fibrinopeptides was also investigated with bovine thrombin on bovine fibrinogen at the above 3 pH values. Significant differences were found between the human and the bovine enzyme. C1 CSIC,INST QUIM FIS ROCASOLANO,E-28006 MADRID,SPAIN. RP MIHALYI, E (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 20 TC 9 Z9 9 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 MAY 14 PY 1991 VL 30 IS 19 BP 4753 EP 4762 DI 10.1021/bi00233a017 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FL550 UT WOS:A1991FL55000017 PM 2029517 ER PT J AU LEMAISTRE, CF ROSENBLUM, MG REUBEN, JM PARKINSON, DR MENEGHETTI, CM PARKER, K SHAW, JP DEISSEROTH, AB WOODWORTH, T AF LEMAISTRE, CF ROSENBLUM, MG REUBEN, JM PARKINSON, DR MENEGHETTI, CM PARKER, K SHAW, JP DEISSEROTH, AB WOODWORTH, T TI THERAPEUTIC EFFECTS OF GENETICALLY ENGINEERED TOXIN (DAB486IL-2) IN PATIENT WITH CHRONIC LYMPHOCYTIC-LEUKEMIA SO LANCET LA English DT Note ID EXPRESSION; RECEPTORS; CELL AB In DAB486IL-2 the receptor-binding domain of native diphtheria toxin is replaced by human IL-2 sequences. This recombinant fusion protein is selectively cytotoxic for cells bearing high-affinity IL-2 receptors-eg, leukaemic cells. A patient with chronic lymphocytic leukaemia who did not respond to gamma interferon and conventional antileukaemic drugs has responded to DAB486IL-2. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX 77025. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CLIN IMMUNOL & BIOL THERAPY,HOUSTON,TX 77025. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT LAB MED,HOUSTON,TX 77025. NCI,BETHESDA,MD 20892. SERAGEN INC,HOPKINTON,MA. RP LEMAISTRE, CF (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED HEMATOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 9 TC 32 Z9 32 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 11 PY 1991 VL 337 IS 8750 BP 1124 EP 1125 DI 10.1016/0140-6736(91)92788-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FL124 UT WOS:A1991FL12400005 PM 1674015 ER PT J AU WILCOX, AJ WEINBERG, CR AF WILCOX, AJ WEINBERG, CR TI TEA AND FERTILITY SO LANCET LA English DT Letter ID CAFFEINATED BEVERAGES RP WILCOX, AJ (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 6 TC 8 Z9 8 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 11 PY 1991 VL 337 IS 8750 BP 1159 EP 1160 DI 10.1016/0140-6736(91)92825-M PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FL124 UT WOS:A1991FL12400032 PM 1674032 ER PT J AU POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR AF POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN LIVER-TYPE 6-PHOSPHOFRUCTOKINASE (PFKL) GENE SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,NIMH,ROOM 131,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 3 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 11 PY 1991 VL 19 IS 9 BP 2517 EP 2517 DI 10.1093/nar/19.9.2517 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM145 UT WOS:A1991FM14500061 PM 1828296 ER PT J AU MIZUGUCHI, M YAMADA, M KIM, SU RHEE, SG AF MIZUGUCHI, M YAMADA, M KIM, SU RHEE, SG TI PHOSPHOLIPASE-C ISOZYMES IN NEURONS AND GLIAL-CELLS IN CULTURE - AN IMMUNOCYTOCHEMICAL AND IMMUNOCHEMICAL STUDY SO BRAIN RESEARCH LA English DT Article DE PHOSPHOINOSITIDE 2ND-MESSENGER SYSTEM; TISSUE CULTURE; IMMUNOCYTOCHEMISTRY; IMMUNOBLOTTING; NEURON; GLIA ID PROTEIN KINASE-C; BOVINE BRAIN; RAT-BRAIN; IMMUNOHISTOCHEMICAL LOCALIZATION; TYROSINE PHOSPHORYLATION; PURIFICATION; MESSENGER; FORMS; INTERNALIZATION; INVIVO AB Expression of 3 brain isozymes of phospholipase (PLC-beta, PLC-gamma and PLC-sigma) was investigated in relation to cell types found in rat CNS cultures. Immunoreactivity of cultured neurons, astrocytes and oligodendrocytes was demonstrated for all of the 3 isozymes by immunocytochemical staining and immunoblotting, with some differences in reaction intensity. Immunoblotting revealed that the level of expression was neurons > oligodendrocytes > astrocytes for PLC-beta and PLC-gamma, and astrocytes > oligodendrocytes > neurons for PLC-sigma. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RP MIZUGUCHI, M (reprint author), UNIV BRITISH COLUMBIA,DEPT MED,DIV NEUROL,2211 WESBROOK MALL,VANCOUVER V6T 1W5,BC,CANADA. NR 35 TC 29 Z9 29 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 MAY 10 PY 1991 VL 548 IS 1-2 BP 35 EP 40 DI 10.1016/0006-8993(91)91103-8 PG 6 WC Neurosciences SC Neurosciences & Neurology GA FP170 UT WOS:A1991FP17000006 PM 1868346 ER PT J AU CALIGURI, EJ JOHANNESSEN, JN AF CALIGURI, EJ JOHANNESSEN, JN TI SELECTIVE DECREASE IN EXTRACELLULAR DOPAC CONCENTRATIONS IN RAT STRIATUM FOLLOWING INVIVO DIALYSIS WITH LOW CONCENTRATIONS OF MPP+ SO BRAIN RESEARCH LA English DT Article DE DOPAMINE; DIALYSIS, INVIVO; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYLPYRIDINIUM; PARKINSONISM; SUBSTANTIA NIGRA ID 1-METHYL-4-PHENYLPYRIDINIUM ION MPP+; MONOAMINE-OXIDASE; INDUCED PARKINSONISM; BRAIN MITOCHONDRIA; DOPAMINE; MPTP; METABOLISM; INHIBITORS; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE AB Using the technique of in vivo dialysis, 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was applied to the rat striatum and the effects of this treatment on the efflux of striatal dopamine (DA) and metabolites were monitored. The inclusion of low concentrations of MPP+ (1 and 10-mu-M) in the dialysis solution caused a progressive decrease in the efflux of dihydroxyphenylacetic acid (DOPAC), the major deamination product of DA, while homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) remained unchanged. Unlike the effects of dialysis with millimolar concentrations of MPP+, a large increase in the efflux of striatal DA was not observed. The effect of dialysis with 1-mu-M MPP+ was blocked if 1-mu-M GBR 12909, a specific DA reuptake blocker, was included in the dialysis fluid, suggesting uptake of MPP+ into striatal DA terminals mediated this effect. C1 NIMH,CLIN SCI LAB,BLDG 10-3D-40,BETHESDA,MD 20892. NR 27 TC 5 Z9 5 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 MAY 10 PY 1991 VL 548 IS 1-2 BP 94 EP 99 DI 10.1016/0006-8993(91)91110-M PG 6 WC Neurosciences SC Neurosciences & Neurology GA FP170 UT WOS:A1991FP17000013 PM 1714336 ER PT J AU LAVORGNA, G UEDA, H CLOS, J WU, C AF LAVORGNA, G UEDA, H CLOS, J WU, C TI FTZ-F1, A STEROID-HORMONE RECEPTOR LIKE PROTEIN IMPLICATED IN THE ACTIVATION OF FUSHI-TARAZU SO SCIENCE LA English DT Article ID DROSOPHILA-MELANOGASTER; ESTROGEN-RECEPTOR; AMINO-ACIDS; GENE KNIRPS; SUPERFAMILY; DNA; SEGMENTATION; SEQUENCE; MEMBER; IDENTIFICATION AB The Drosophila homeobox segmentation gene fushi tarazu (ftz) is expressed in a seven-stripe pattern during early embryogenesis. This characteristic pattern is largely specified by the zebra element located immediately upstream of the ftz transcriptional start site. The FTZ-F1 protein, one of multiple DNA binding factors that interacts with the zebra element, is implicated in the activation of ftz transcription, especially in stripes 1, 2, 3, and 6. An FTZ-F1 complementary DNA has been cloned by recognition site screening of a Drosophila expression library. The identity of the FTZ-F1 complementary DNA clone was confirmed by immunological cross-reaction with antibodies to FTZ-F1 and by sequence analysis of peptides from purified FTZ-F1 protein. The predicted amino acid sequence of FTZ-F1 revealed that the protein is a member of the nuclear hormone receptor superfamily. This finding raises the possibility that a hormonal ligand affects the expression of a homeobox segmentation gene early in embryonic development. C1 NATL INST GENET,MISHIMA,SHIZUOKA 411,JAPAN. RP LAVORGNA, G (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. RI UEDA, Hitoshi/B-1455-2011 NR 49 TC 246 Z9 254 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 10 PY 1991 VL 252 IS 5007 BP 848 EP 851 DI 10.1126/science.1709303 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FL123 UT WOS:A1991FL12300048 PM 1709303 ER PT J AU CHARNAS, LR BERNARDINI, I RADER, D HOEG, JM GAHL, WA AF CHARNAS, LR BERNARDINI, I RADER, D HOEG, JM GAHL, WA TI CLINICAL AND LABORATORY FINDINGS IN THE OCULOCEREBRORENAL SYNDROME OF LOWE, WITH SPECIAL REFERENCE TO GROWTH AND RENAL-FUNCTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SERUM CREATININE CONCENTRATION; HIGH-DENSITY-LIPOPROTEIN; FANCONI SYNDROME; LENS EXAMINATION; CARNITINE; DISEASE; CYSTINOSIS; CHILDREN; PROGRESSION; DEFICIENCY AB Background. The oculocerebrorenal syndrome of Lowe is an X-linked disorder whose clinical manifestations include congenital cataracts, mental retardation, and renal tubular dysfunction. We investigated growth, renal function, and serum chemistry values in patients with the oculocerebrorenal syndrome to determine the natural history of the disorder and its heterogeneity with respect to these characteristics. Methods. Twenty-three patients with the oculocerebrorenal syndrome, ranging in age from 4 months to 31 years, were examined. Height was compared with bone age. Renal function was assessed by measurements of proteinuria, urinary volume, and fractional excretions of potassium, phosphate, carnitine, and amino acids. Creatinine clearance was determined as a measure of glomerular function. Results. In the oculocerebrorenal syndrome, linear growth decreases after one year of age; bone age lies between chronologic age and height age. Renal dysfunction occurs in the first year of life, characterized by proteinuria (mean [+/- SD], 1.38 +/- 0.77 g of urinary protein per square meter of body-surface area per day; normal, less-than-or-equal-to 0.10), generalized aminoaciduria (mean, 686 +/- 505-mu-mol of urinary amino acid per kilogram of body weight per day; normal, 94 +/- 45), carnitine wasting (mean fractional excretion, 0.10 +/- 0.05; normal, 0.03 +/- 0.01), and phosphaturia progressing into the third decade. Urinary wasting of individual amino acids is milder than in cystinosis, and branched-chain amino acids are relatively spared. Reciprocal serum creatinine levels fall linearly with age, predicting renal failure in the fourth decade. Concentrations of the muscle enzymes creatine kinase, aspartate aminotransferase, and lactate dehydrogenase, as well as of total serum protein, serum alpha-2-globulin, and high-density lipoprotein cholesterol, are elevated. Conclusions. Renal glomerular deterioration is slowly progressive in the oculocerebrorenal syndrome. Renal tubular dysfunction begins early and persists; most patients require alkalinization therapy, and many benefit from supplemental potassium, phosphate, calcium, or carnitine. Serum enzyme elevations suggest muscle involvement in the oculocerebrorenal syndrome. C1 NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BLDG 10,RM 9S242,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,NEUROGENET UNIT,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. NR 55 TC 61 Z9 63 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 MAY 9 PY 1991 VL 324 IS 19 BP 1318 EP 1325 DI 10.1056/NEJM199105093241904 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA FK186 UT WOS:A1991FK18600004 PM 2017228 ER PT J AU NASHED, NT BALANI, SK LONCHARICH, RJ SAYER, JM SHIPLEY, DY MOHAN, RS WHALEN, DL JERINA, DM AF NASHED, NT BALANI, SK LONCHARICH, RJ SAYER, JM SHIPLEY, DY MOHAN, RS WHALEN, DL JERINA, DM TI SOLVOLYSIS OF K-REGION ARENE OXIDES - SUBSTITUENT EFFECTS ON REACTIONS OF BENZ[A]ANTHRACENE 5,6-OXIDE SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; PERFORMANCE LIQUID-CHROMATOGRAPHY; CHIRAL STATIONARY PHASES; ABSOLUTE-CONFIGURATION; MICROSOMAL-ENZYMES; EPOXIDE HYDROLYSIS; TRANS-DIHYDRODIOLS; CHLORIDE-ION; RESOLUTION; ENANTIOMERS AB The solvolytic reactivity and products formed from benz[a]anthracene 5,6-oxide (BA-O) on substitution of a methyl group at positions 1 (1-MBA-O), 4 (4-MBA-O), 7 (7-MBA-O), 11 (11-MBA-O), and 12 (12-MBA-O), on 7,12-dimethyl substitution (7,12-DMBA-O), and on 7-bromo substitution in 1:9 dioxane-water and in methanol at 25-degrees-C are reported. These substitutions result in > 150-fold differences in their rates of acid-catalyzed solvolysis and cause marked changes in the distribution of solvent adducts and phenols resulting from isomerization. Optically pure BA-O, 7-MBA-O, 12-MBA-O, and 7,12-DMBA-O as well as their optically pure trans dihydrodiols were utilized to determine the point of attack by water in the hydrolysis reactions. In general, the reactions in aqueous dioxane (0.1 M NaClO4) obeyed the rate equation k(obsd) = k(H)[H+] + k0, where k(H) is the second-order rate constant for acid-catalyzed reaction and k0 is the first-order rate constant for spontaneous reaction, to provide biphasic pH-rate profiles. When ionic strength was maintained with 0.5 M KCl, however, more complex pH-rate profiles were observed for some of the arene oxides due to attack of chloride on the neutral epoxide to produce steady-state concentrations of chlorohydrins. Rate enhancement on methyl substitution is largest (k(H), ca. 5-fold) when the methyl group is present in the hindered bay region (C1 or C-12) or adjacent to the epoxide at C-7. The combined effect of two methyl groups (7,12-DMBA-O) is additive (ca. 25-fold). Theoretical calculations (molecular mechanics by PCMODEL-PI and ab initio by GAUSSIAN 86 and 88 programs) of carbocation stability indicate the importance of steric factors in determining relative reactivity and types of products formed from substituted benz[a]anthracene 5,6-oxides. C1 NIH,DIV COMP RES & TECHNOL,MOLEC GRAPH & SIMULAT LAB,BETHESDA,MD 20892. UNIV MARYLAND,DEPT CHEM,CHEM DYNAM LAB,CATONSVILLE,MD 21228. RP NASHED, NT (reprint author), NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 50 TC 25 Z9 25 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 8 PY 1991 VL 113 IS 10 BP 3910 EP 3919 DI 10.1021/ja00010a036 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA FL177 UT WOS:A1991FL17700036 ER PT J AU AXELROD, J AF AXELROD, J TI MICROSOMAL-ENZYMES THAT METABOLIZE DRUGS - A CITATION-CLASSIC COMMENTARY ON AN ENZYME FOR THE DEAMINATION OF SYMPATHOMIMETIC AMINES - PROPERTIES AND DISTRIBUTION - THE ENZYMATIC DEAMINATION OF AMPHETAMINE (BENZEDRINE) - ENZYMATIC DEMETHYLATION OF SYMPATHOMIMETIC AMINES - THE ENZYMATIC DEMETHYLATION OF EPHEDRINE BY AXELROD,J. SO CURRENT CONTENTS/LIFE SCIENCES LA English DT Article RP AXELROD, J (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU INST SCI INFORM INC PI PHILADELPHIA PA 3501 MARKET ST, PHILADELPHIA, PA 19104 SN 0011-3409 J9 CC/LIFE SCI PD MAY 6 PY 1991 IS 18 BP 11 EP 11 PG 1 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA FH002 UT WOS:A1991FH00200002 ER PT J AU HORN, VJ AMBUDKAR, IS BAUM, BJ AF HORN, VJ AMBUDKAR, IS BAUM, BJ TI HIGH-AFFINITY QUINUCLIDINYL BENZILATE BINDING TO RAT PAROTID MEMBRANES REQUIRES MUSCARINIC RECEPTOR - G-PROTEIN INTERACTIONS SO FEBS LETTERS LA English DT Article DE ANTAGONIST; RECEPTOR; G-PROTEIN; PAROTID; AIF4-; GTP-GAMMA-S ID BETA-ADRENERGIC RECEPTORS; ADENYLATE-CYCLASE SYSTEM; ANTAGONIST BINDING; GUANINE-NUCLEOTIDE; RECIPROCAL MODULATION; REGULATORY COMPONENT; RECONSTITUTION; AGONIST; INHIBITION AB The binding of the non-selective muscarinic antagonist [H-3]quinuclidinyl benzilate (QNB) to rat parotid membranes was characterized. Under equilibrium conditions, [H-3]QNB bound to a homogenous population of muscarinic receptors (K(d), 118 +/- 19 pM; B(max), 572 +/- 42 fmol/mg membrane protein, n = 12). The addition of G protein activators AlF4- or guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) + Mg2+ increased the K(d) by 77 +/- 7% (n = 4, P < 0.05) and 83 +/- 27% (n = 7, P < 0.05), respectively, without a change in the B(max) or homogeneity of the binding site. GTP-gamma-S added without exogenous Mg2+ did not affect [H-3]QNB binding. Thus, optimal QNB binding requires a muscarinic receptor/G protein interaction. RP HORN, VJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1N-113,BETHESDA,MD 20892, USA. NR 26 TC 4 Z9 4 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 MAY 6 PY 1991 VL 282 IS 2 BP 289 EP 292 DI 10.1016/0014-5793(91)80497-Q PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FM908 UT WOS:A1991FM90800018 PM 1903714 ER PT J AU CHOUDHURY, GG SYLVIA, VL WANG, LM PIERCE, J SAKAGUCHI, AY AF CHOUDHURY, GG SYLVIA, VL WANG, LM PIERCE, J SAKAGUCHI, AY TI THE KINASE INSERT DOMAIN OF COLONY STIMULATING FACTOR-I RECEPTOR IS DISPENSABLE FOR CSF-1 INDUCED PHOSPHATIDYLCHOLINE HYDROLYSIS SO FEBS LETTERS LA English DT Article DE COLONY STIMULATING FACTOR-I RECEPTOR; TYROSINE KINASE; PHOSPHATIDYLCHOLINE HYDROLYSIS; NIH-3T3 CELL ID FACTOR-I RECEPTOR; PHOSPHOLIPASE-C-GAMMA; TYROSINE PHOSPHORYLATION; PHOSPHATIDYLINOSITOL KINASE; SIGNAL TRANSDUCTION; DNA-SYNTHESIS; CELLS; PDGF; PROLIFERATION; DIFFERENTIATION AB Mouse NIH 3T3 fibroblasts transfected with human colony stimulating factor-1 receptor produced diacylglycerol in response to CSF1 and this correlated with elevated phosphatidylcholine hydrolyzing activity measured in an in vitro assay. Treatment of cells with the isoflavone derivative genistein attenuated PC hydrolysis in vitro suggesting a role for CSF1R tyrosine kinase activity. A CSF1R mutant lacking 67 amino acids of the kinase insert domain, which may affect the association of receptor with certain substrates, stimulated PC hydrolysis in response to CSF1. Coupling to PC hydrolysis is likely a general property of CSF1R and the kinase insert domain is dispensable for this activity. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIA NIH HHS [P01-AG06872] NR 27 TC 20 Z9 20 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 MAY 6 PY 1991 VL 282 IS 2 BP 351 EP 354 DI 10.1016/0014-5793(91)80511-Z PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FM908 UT WOS:A1991FM90800032 PM 1828037 ER PT J AU DATA, RE WILLIAMS, SB ROBERTS, DD GRALNICK, HR AF DATA, RE WILLIAMS, SB ROBERTS, DD GRALNICK, HR TI PLATELETS ADHERE TO SULFATIDES BY VONWILLEBRAND-FACTOR DEPENDENT AND INDEPENDENT MECHANISMS SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID SOLID-STATE LACTOPEROXIDASE; THROMBOSPONDIN BINDS; FACTOR-VIII; ADHESION; FIBRONECTIN; COLLAGEN; PROTEIN; GLYCOLIPIDS; FIBRINOGEN; LAMININ AB Unstimulated human platelets from normal volunteers adhere to sulfatides (galactosylceramide-I3-sulfate) as single cells but do not adhere appreciably to other lipids including gangliosides, neutral glycolipids, phospholipids or cholesterol-3-SO4. Platelet adhesion to sulfatide is saturable and dose-dependent, reaches maximal levels in 90 to 120 min, and is not divalent cation-dependent. Because sulfatides bind von Willebrand factor (vWf) with specificity and high affinity and platelet adhesion to structurally related sulfated glycolipids is approximately proportionate to their ability to bind vWf, we examined whether vWf mediates platelet adhesion to sulfatides. Platelets from a patient with severe Type I von Willebrand's disease adhere poorly to sulfatides. However, adhesion to levels seen with normal platelets is restored by the addition of vWf. Adhesion of normal platelets can be partially inhibited by a monospecific antibody to vWf. Normal platelet adhesion to sulfatides, however, is not increased following preincubation with vWf. Both vWf binding and platelet adhesion to sulfatides can be inhibited by the sulfated polysaccharide dextran sulfate at low concentration, fucoidan at high concentrations, but not by heparin, fibrinogen, fibronectin, or the synthetic peptides Gly-Arg-Gly-Asp-Ser-Pro or Gly-Arg-Gly-Glu-Ser-Pro. Thus, adhesion to sulfatides appears to be of two types; vWf dependent (50-75%) and vWf independent (25-50%). C1 NCI, CTR CLIN,DEPT CLIN PATHOL,HEMATOL SERV,10-2C390, ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 34 TC 7 Z9 7 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD MAY 6 PY 1991 VL 65 IS 5 BP 581 EP 587 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA FM442 UT WOS:A1991FM44200022 PM 1871720 ER PT J AU PARK, MH WOLFF, EC SMITMCBRIDE, Z HERSHEY, JWB FOLK, JE AF PARK, MH WOLFF, EC SMITMCBRIDE, Z HERSHEY, JWB FOLK, JE TI COMPARISON OF THE ACTIVITIES OF VARIANT FORMS OF EIF-4D - THE REQUIREMENT FOR HYPUSINE OR DEOXYHYPUSINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EUKARYOTIC INITIATION FACTOR-4D; HAMSTER OVARY CELLS; PROTEIN-SYNTHESIS; AMINO-ACID; RABBIT RETICULOCYTES; FACTOR 4D; BIOSYNTHESIS; PURIFICATION; SPERMIDINE; POLYAMINES AB Eukaryotic protein synthesis initiation factor 4D (eIF-4D) (current nomenclature, eIF-5A) contains the unique amino acid hypusine (N-epsilon-(4-amino-2-hydroxy-butyl)lysine). The first step in hypusine biosynthesis, i.e. the formation of the intermediate, deoxyhypusine (N-epsilon-(4-aminobutyl)lysine), was carried out in vitro using spermidine, deoxyhypusine synthase, and ec-eIF-4D(Lys), an eIF-4D precursor prepared by over-expression of human eIF-4D cDNA in Escherichia coli. In a parallel reaction, using N-(3-aminopropyl)cadaverine in place of spermidine, a variant form of eIF-4D containing homodeoxyhypusine (N-epsilon-(5-aminopentyl)lysine) was prepared. Evidence that N-(3-amino-propyl)cadaverine can also act as the amine substrate for deoxyhypusine synthase in intact cells was obtained by incubating putrescine- and spermidine-depleted Chinese hamster ovary cells with [H-3]cadaverine. In these cells, in which [H-3]cadaverine is readily converted to N-(3-aminopropyl) [H-3]cadaverine, small amounts of [H-3]homodeoxyhypusine and another H-3-labeled compound, presumed to be N-epsilon-(5-amino-2-hydroxy[H-3]pentyl)lysine, were found. eIF-4D stimulates methionyl-puromycin synthesis, an in vitro model assay for translation initiation. Whereas the unmodified precursor ec-eIF-4D(Lys) appeared inactive, the deoxyhypusine-containing form provided a significant degree of stimulation. The variant form containing homodeoxyhypusine, on the other hand, showed little or no activity. These findings emphasize the importance of hypusine or deoxyhypusine for the biological activity of eIF-4D and demonstrate the influence of both the length and chemical nature of its amino alkyl side chain. C1 UNIV CALIF DAVIS,SCH MED,DEPT BIOL CHEM,DAVIS,CA 95616. RP PARK, MH (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,BLDG 30,RM 211,BETHESDA,MD 20892, USA. RI Smit-McBride, Zeljka/F-5524-2010 FU NIGMS NIH HHS [GM 22135] NR 38 TC 56 Z9 57 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1991 VL 266 IS 13 BP 7988 EP 7994 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK441 UT WOS:A1991FK44100008 PM 1850732 ER PT J AU ANDERSON, KS MILES, EW JOHNSON, KA AF ANDERSON, KS MILES, EW JOHNSON, KA TI SERINE MODULATES SUBSTRATE CHANNELING IN TRYPTOPHAN SYNTHASE - A NOVEL INTERSUBUNIT TRIGGERING MECHANISM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; ALPHA-SUBUNIT; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; TETRAHEDRAL INTERMEDIATE; PHOSPHOGLYCERATE KINASE; SALMONELLA-TYPHIMURIUM; CATALYTIC MECHANISM; BETA-ELIMINATION; ENZYME COMPLEX; B-PROTEIN AB Tryptophan synthase, an alpha-2-beta-2 complex, is a classic example of an enzyme that is thought to "channel" a metabolic intermediate (indole) from the active site of the alpha-subunit to the active site of the beta-subunit. We now examine the kinetics of substrate channeling by tryptophan synthase directly by chemical quench-flow and stopped-flow methods. The conversion of indole-3-glycerol phosphate (IGP) to tryptophan at the active site proceeds at a rate of 24 s-1, which is limited by the rate of cleavage of IGP to produce indole (alpha-reaction). In a single turnover experiment monitoring the conversion of radiolabeled IGP to tryptophan, only a trace of indole is detectable (less-than-or-equal-to 1% of the IGP), implying that the reaction of indole to form tryptophan must be quite fast (greater-than-or-equal-to 1000 s-1). The rate of reaction of indole from solution is much too slow (40 s-1 under identical conditions) to account for the negligible accumulation of indole in a single turnover. Therefore, the indole produced at the alpha-site must be rapidly channeled to the beta-site, where it reacts with serine to form tryptophan: channeling and the reaction of indole to form tryptophan must each occur at rates greater-than-or-equal-to 1000 s-1. Steady-state turnover is limited by the slow rate of tryptophan release (8 s-1). In the absence of serine, the cleavage of IGP to indole is limited by a change in protein conformation at a rate of 0.16 s-1. When the alpha-beta-reaction is initiated by mixing enzyme with IGP and serine simultaneously, there is a lag in the cleavage of IGP and formation of tryptophan. The kinetics of the lag correspond to the rate of formation of the aminoacrylate in the reaction of serine with pyridoxal phosphate at the beta-site, measured by stopped-flow methods (45 s-1). There is also a change in protein fluorescence, suggestive of a change in protein conformation, occurring at the same rate. Substitution of cysteine for serine leads to a longer lag in the kinetics of IGP cleavage and a correspondingly slower rate of formation of the aminoacrylate (6 s-1). Thus, the reaction of serine at the beta-site modulates the alpha-reaction such that the formation of the aminoacrylate leads to a change in protein conformation that is transmitted to the alpha-site to enhance the rate of IGP cleavage 150-fold. Analysis of a mutant in the beta-subunit (E109D) shows that the rate of reaction of indole at the beta-site is decreased 300-fold, supporting the postulated role of Glu-109 in deprotonating indole to facilitate its reaction with the aminoacrylate. Kinetic analysis of the conversion of IGP and serine to tryptophan catalyzed by the mutant enzyme demonstrates the formation and decay of a significant fraction of indole in a single turnover due to the slower rate of condensation of indole with the aminoacrylate. Taken together, these data demonstrate directly that efficient channeling of indole is a consequence of three features of the reaction kinetics. 1) The rate of diffusion of indole through the channel is very fast; 2) the reaction of indole to form tryptophan at the beta-site is fast and largely irreversible; and 3) the reaction of serine at the beta-site modulates the formation of indole at the alpha-site or in the tunnel such that indole is not produced until serine has reacted with pyridoxal phosphate to form the highly reactive aminoacrylate. This intersubunit communication keeps the alpha and beta-reactions in phase so that indole does not accumulate at the alpha-site. It is only the combination of these three aspects of the reaction kinetics that leads to efficient channeling of the indole by maintaining a low concentration of indole bound to the enzyme. C1 NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. PENN STATE UNIV,DEPT MOLEC & CELL BIOL,UNIVERSITY PK,PA 16802. RP ANDERSON, KS (reprint author), YALE UNIV,SCH MED,DEPT PHARMACOL,333 CEDAR ST,NEW HAVEN,CT 06510, USA. FU NIGMS NIH HHS [GM26726] NR 38 TC 143 Z9 143 U1 3 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1991 VL 266 IS 13 BP 8020 EP 8033 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK441 UT WOS:A1991FK44100013 PM 1902468 ER PT J AU CHOUDHURY, GG WANG, LM PIERCE, J HARVEY, SA SAKAGUCHI, AY AF CHOUDHURY, GG WANG, LM PIERCE, J HARVEY, SA SAKAGUCHI, AY TI A MUTATIONAL ANALYSIS OF PHOSPHATIDYLINOSITOL-3-KINASE ACTIVATION BY HUMAN COLONY-STIMULATING FACTOR-I RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOLIPASE-C-GAMMA; FACTOR-I RECEPTOR; HEMATOPOIETIC GROWTH-FACTORS; TYROSINE KINASE-ACTIVITY; PDGF RECEPTOR; SIGNAL TRANSDUCTION; FACTOR CSF-1; PROTEIN; CELLS; PHOSPHORYLATION AB Colony-stimulating factor-1 (CSF1) is a cell lineage-specific hemopoietin required for the growth, differentiation, and survival of macrophages and their precursors. The human CSF1 receptor (CSF1R) is a 150-kDa transmembrane glycoprotein whose cytoplasmic tyrosine kinase domain is split by a kinase insert (KI) region of approximately 70 amino acids. We tested the ability of CSF1R KI domain deletion mutants to stimulate phosphatidylinositol-3-kinase (PtdIns-3-kinase), an enzyme whose activity is augmented by tyrosine kinase oncogenes and receptor tyrosine kinases, and to support mitogenesis in transfected cells. Receptor immunoprecipitates from CSF1-stimulated cells contained > 5-fold more PtdIns-3-kinase activity compared to nonstimulated cells. High performance liquid chromatography analysis of the PtdIns-3-kinase product scraped from thin layer chromatography plates indicated that PtdIns-3-P was produced. CSF1R KI domain deletion mutants retained tyrosine kinase activity in vitro. Receptor immunoprecipitates of two partially overlapping 28 and 30 amino acid KI deletion mutants of CSF1R retained some PtdIns-3-kinase activity, in contrast to immunoprecipitates of CSF1R lacking 67 amino acids of the KI domain. Each deletion mutant stimulated CSF1-dependent DNA synthesis in transfected cells at much reduced levels compared to wild-type receptor expressing cells. These data suggest a role for the CSF1R KI domain in PtdIns-3-kinase association and for CSF1-induced thymidine incorporation into DNA. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIA NIH HHS [P01-AG06872] NR 47 TC 56 Z9 56 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1991 VL 266 IS 13 BP 8068 EP 8072 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK441 UT WOS:A1991FK44100020 PM 1850734 ER PT J AU TSAI, SC ADAMIK, R TSUCHIYA, M CHANG, PP MOSS, J VAUGHAN, M AF TSAI, SC ADAMIK, R TSUCHIYA, M CHANG, PP MOSS, J VAUGHAN, M TI DIFFERENTIAL EXPRESSION DURING DEVELOPMENT OF ADP-RIBOSYLATION FACTORS, 20-KDA GUANINE NUCLEOTIDE-BINDING PROTEIN ACTIVATORS OF CHOLERA-TOXIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENYLATE-CYCLASE; REGULATORY COMPONENT; RIBOSYLTRANSFERASE ACTIVITY; NUCLEOSIDE TRIPHOSPHATES; MACROMOLECULAR FACTOR; ALPHA-SUBUNIT; BOVINE BRAIN; GTP; PURIFICATION; TRANSDUCIN AB Cholera toxin exerts its effects on cells in large part through the ADP-ribosylation of guanine nucleotide-binding proteins. Toxin-catalyzed ADP-ribosylation is enhanced by approximately 20-kDa guanine nucleotide-binding proteins termed ADP-ribosylation factors (ARFs), which are allosteric activators of the toxin catalytic unit. Rabbit antiserum against a purified bovine brain ARF (sARF II) reacted on immunoblots with two approximately 20-kDa ARF-like proteins (sARF I and II) in tissue extracts from bovine, rat, frog, and chicken. Levels of ARF were higher in brain than in non-neural tissues. In rat brain, on the second postnatal day, amounts of sARF I and II were similar. By the 10th postnatal day and thereafter, sARF II predominated. Relative levels of ARF determined by immunoreactivity were in agreement with levels assessed in functional assays of cholera toxin-catalyzed ADP-ribosylation. Based on nucleotide and deduced amino acid sequences of human and bovine cDNAs, there appear to be at least six different ARF-like genes. Northern blots of rat brain poly(A)+ RNA were hybridized with cDNA and oligonucleotide probes specific for each of the human and bovine ARF genes. From the second to the 27th postnatal day, ARF 3 mRNA increased, whereas mRNAs for ARFs 2 and 4 decreased; and those for ARFs 1, 5, and 6 were apparently unchanged. Partial amino acid sequence of sARF II is consistent with it being either the ARF 1 or 3 gene product. The developmental changes in rat brain ARF parallel neuronal maturation and synapse formation. RP TSAI, SC (reprint author), NHLBI,CELLULAR METAB LAB,RM 5N-307,BLDG 10,BETHESDA,MD 20892, USA. NR 49 TC 53 Z9 54 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1991 VL 266 IS 13 BP 8213 EP 8219 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK441 UT WOS:A1991FK44100042 PM 1902473 ER PT J AU HERKENHAM, M LYNN, AB DECOSTA, BR RICHFIELD, EK AF HERKENHAM, M LYNN, AB DECOSTA, BR RICHFIELD, EK TI NEURONAL LOCALIZATION OF CANNABINOID RECEPTORS IN THE BASAL GANGLIA OF THE RAT SO BRAIN RESEARCH LA English DT Article DE TETRAHYDROCANNABINOL; [H-3]CP-55,940; D1-RECEPTOR; D2-RECEPTOR; DOPAMINE RECEPTOR; DOPAMINE UPTAKE SITE; CAUDATE-PUTAMEN; SUBSTANTIA NIGRA; IBOTENATE; 6-HYDROXYDOPAMINE ID SENSITIVE ADENYLATE-CYCLASE; FREELY-MOVING RATS; SUBSTANTIA NIGRA; MULTIPLE-SCLEROSIS; NUCLEUS-ACCUMBENS; D2 RECEPTORS; DOPAMINE; BRAIN; DELTA-9-TETRAHYDROCANNABINOL; D1 AB Cannabinoid receptors have recently been characterized and localized using a high-affinity radiolabeled cannabinoid analog in section binding assays. Is rat brain, the highest receptor densities are in the globus pallidus and substantia nigra pars reticulata. Receptors are also dense in the caudate-putamen. In order to determine the neuronal localization of these receptors, selective lesions of key striatal afferent and efferent systems were made. Striatal neurons and efferent projections were selectively destroyed by unilateral infusion of ibotenic acid into the caudate-putamen. The nigrostriatal pathway was selectively destroyed in another set of animals by infusion of 6-hydroxydopamine into the medial forebrain bundle. After 2- or 4-week survivals, slide-mounted brain sections were incubated with ligands selective for cannabinoid ([H-3]CP 55,940), dopamine D1 ([H-3]SCH-23390) and D2 ([H-3]raclopride) receptors, and dopamine uptake sites ([H-3]GBR-12935). Slides were exposed to H-3-sensitive film. The resulting autoradiography showed ibotenate-induced losses of cannabinoid, D1 and D2 receptors in the caudate-putamen and topographic losses of cannabinoid and D1 receptors in the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata at both survivals. Four weeks after medial forebrain bundle lesions (which resulted in amphetamine-induced rotations), there was loss of dopamine uptake sites in the striatum and substantia nigra pars compacta but no change in cannabinoid receptor binding. The data show that cannabinoid receptors in the basal ganglia are neuronally located on striatal projection neurons, including their axons and terminals. Cannabinoid receptors may be co-localized with D1 receptors on striatonigral neurons. Cannabinoid receptors are not localized on dopaminergic nigrostriatal cell bodies or terminals. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP HERKENHAM, M (reprint author), NIMH,FUNCT NEUROANAT SECT,BLDG 36,RM 2D-15,BETHESDA,MD 20892, USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 44 TC 382 Z9 388 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 3 PY 1991 VL 547 IS 2 BP 267 EP 274 DI 10.1016/0006-8993(91)90970-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA FL230 UT WOS:A1991FL23000011 PM 1909204 ER PT J AU MIHALY, A ORAVECZ, T OLAH, Z RAPP, UR AF MIHALY, A ORAVECZ, T OLAH, Z RAPP, UR TI IMMUNOHISTOCHEMICAL LOCALIZATION OF RAF PROTEIN-KINASE IN DENDRITIC SPINES AND SPINE APPARATUSES OF THE RAT CEREBRAL-CORTEX SO BRAIN RESEARCH LA English DT Note DE PROTOONCOGENE; DENDRITIC SPINE; SPINE APPARATUS; PROTEIN KINASE; IMMUNOHISTOCHEMISTRY ID LONG-TERM POTENTIATION; ELECTRON-MICROSCOPIC LOCALIZATION; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; DENTATE GYRUS; FAMILY; CELLS; BRAIN; ACTIVATION; ONCOGENE AB The ultrastructural localization of raf protein (product of the raf protooncogene) in the neocortex, pyriform cortex and hippocampus of the rat has been investigated by means of pre-embedding immunohistochemistry. Specificity of the antiserum was tested with Western blotting. Besides the immunoreactivity of the dendrites, remarkably strong immunostaining of the dendritic spines and spine apparatuses was noted in each of the investigated areas. The postsynaptic densities were also stained. Since raf proteins are serine/threonine-specific protein kinases, our findings could be important steps toward the understanding of dendritic spine plasticity. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. MAX PLANCK INST BIOPHYS CHEM,DEPT NEUROBIOL,W-3400 GOTTINGEN,GERMANY. HUNGARIAN ACAD SCI,BIOL RES CTR,INST GENET,H-6701 SZEGED,HUNGARY. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. RI Mihaly, Andras/K-5096-2012 NR 28 TC 19 Z9 20 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 MAY 3 PY 1991 VL 547 IS 2 BP 309 EP 314 DI 10.1016/0006-8993(91)90976-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA FL230 UT WOS:A1991FL23000017 PM 1884206 ER PT J AU SZALLASI, A BLUMBERG, PM AF SZALLASI, A BLUMBERG, PM TI CHARACTERIZATION OF VANILLOID RECEPTORS IN THE DORSAL HORN OF PIG SPINAL-CORD SO BRAIN RESEARCH LA English DT Note DE [H-3]RESINIFERATOXIN BINDING; VANILLOID RECEPTOR; CAPSAICIN; DORSAL HORN ID ULTRAPOTENT CAPSAICIN ANALOG; SENSORY NEURONS; RESINIFERATOXIN; BINDING; RATS AB Specific [H-3]resiniferatoxin binding is thought to represent the postulated vanilloid (capsaicin) receptor. We have previously characterized [H-3]resiniferatoxin binding to membranes from rat and pig dorsal root ganglia, which contain the cell bodies of capsaicin-sensitive primary afferent neurons. We now demonstrate specific binding of [H-3]resiniferatoxin to particulate preparations from pig dorsal horn, which contains the central nerve endings of the capsaicin-sensitive primary afferent neurons. The K(d) was 0.27 +/- 0.03 nM; the B(max) was 370 +/- 40 fmol/mg protein. Vanilloids of the capsaicin class (capsaicin, piperine, zingerone) and resiniferatoxin class (tinyatoxin, 12-deoxyphorbol 13-phenylacetate 20-homovanillate) inhibited binding with affinities consistent with their relative in vivo potencies. Given the interest in vanilloids as potential non-narcotic analgesic agents, this binding assay affords an attractive approach for characterization of structure-activity relations at spinal vanilloid receptors. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 17 TC 26 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 3 PY 1991 VL 547 IS 2 BP 335 EP 338 DI 10.1016/0006-8993(91)90982-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA FL230 UT WOS:A1991FL23000023 PM 1884211 ER PT J AU KIM, HK KIM, JW ZILBERSTEIN, A MARGOLIS, B KIM, JG SCHLESSINGER, J RHEE, SG AF KIM, HK KIM, JW ZILBERSTEIN, A MARGOLIS, B KIM, JG SCHLESSINGER, J RHEE, SG TI PDGF STIMULATION OF INOSITOL PHOSPHOLIPID HYDROLYSIS REQUIRES PLC-GAMMA-1 PHOSPHORYLATION ON TYROSINE RESIDUES 783 AND 1254 SO CELL LA English DT Article ID EPIDERMAL GROWTH-FACTOR; SIGNAL TRANSDUCTION; C-GAMMA; FACTOR RECEPTOR; KINASES INVIVO; BOVINE BRAIN; SUBSTRATE; CALCIUM; INVITRO AB PDGF binding to its receptor promotes the association with and stimulates the phosphorylation of PLC-gamma-1 at tyrosine and serine residues. Also, PDGF induces an increase in the hydrolysis of inositol phospholipids by PLC. How PDGF activates PLC was investigated by substituting phenylalanine for tyrosine at PLC-gamma-1 phosphorylation sites 771, 783, and 1254 and expressing the mutant enzymes in NIH 3T3 cells. Phenylalanine substitution at Tyr-783 completely blocked the activation of PLC by PDGF, whereas mutation at Tyr-1254 inhibited and mutation at Tyr-771 enhanced the response. Like the wild type, PLC-gamma-1 substituted with phenylalanine at Tyr-783 became associated with the PDGF receptor and underwent phosphorylation at serine residues in response to PDGF. These results suggest that PLC-gamma-1 is the PLC isozyme that mediates PDGF-induced inositol phospholipid hydrolysis, that phosphorylation on Tyr-783 is essential for PLC-gamma-1 activation. These results provide direct evidence that growth factor receptors activate the function of intracellular protein by tyrosine phosphorylation. C1 NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. RORER BIOTECHNOL INC,KING OF PRUSSIA,PA 19406. NYU,SCH MED,DEPT PHARMACOL,NEW YORK,NY 10016. RP KIM, HK (reprint author), NHLBI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 33 TC 503 Z9 508 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 3 PY 1991 VL 65 IS 3 BP 435 EP 441 DI 10.1016/0092-8674(91)90461-7 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FK182 UT WOS:A1991FK18200010 PM 1708307 ER PT J AU KHUSMITH, S CHAROENVIT, Y KUMAR, S SEDEGAH, M BEAUDOIN, RL HOFFMAN, SL AF KHUSMITH, S CHAROENVIT, Y KUMAR, S SEDEGAH, M BEAUDOIN, RL HOFFMAN, SL TI PROTECTION AGAINST MALARIA BY VACCINATION WITH SPOROZOITE SURFACE PROTEIN-2 PLUS CS PROTEIN SO SCIENCE LA English DT Article ID CIRCUMSPOROZOITE PROTEIN; MONOCLONAL-ANTIBODIES; PLASMODIUM-YOELII; MAMMALIAN-CELLS; MURINE MALARIA; EXPRESSION; EFFICIENT; VACCINES; ANTIGENS; SYSTEM AB The circumsporozoite (CS) protein has been the target for development of malaria sporozoite vaccines for a decade. However, immunization with subunit vaccines based on the CS protein has never given the complete protection found after immunization with irradiated sporozoites. BALB/c mice immunized with irradiated Plasmodium yoelii sporozoites produced antibodies and cytotoxic T cells against a 140-kilodalton protein, sporozoite surface protein 2 (SSP2). Mice immunized with P815 cells that had been transfected with either SSP2 or CS genes were partially protected, and those immunized with a mixture of SSP2 and CS transfectants were completely protected against malaria. These studies emphasize the importance of vaccine delivery systems in achieving protection and define a multi-antigen sporozoite vaccine. C1 USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. NR 33 TC 167 Z9 167 U1 2 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 3 PY 1991 VL 252 IS 5006 BP 715 EP 718 DI 10.1126/science.1827210 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FK185 UT WOS:A1991FK18500052 PM 1827210 ER PT J AU OKA, K NAKANO, T TKALCEVIC, GT SCOW, RO BROWN, WV AF OKA, K NAKANO, T TKALCEVIC, GT SCOW, RO BROWN, WV TI MOLECULAR-CLONING OF MOUSE HEPATIC TRIACYLGLYCEROL LIPASE - GENE-EXPRESSION IN COMBINED LIPASE-DEFICIENT (CLD/CLD) MICE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE HEPATIC TRIACYLGLYCEROL LIPASE; CDNA SEQUENCE; COMBINED LIPASE DEFICIENCY; (MOUSE) ID AMINO-ACID-SEQUENCE; LIPOPROTEIN-LIPASE; TRIGLYCERIDE LIPASE; HEPARIN-BINDING; CDNA SEQUENCE; PANCREATIC LIPASE; FRAGMENTS; PLASMA; IDENTIFICATION; LOCALIZATION AB cDNA clones coding for mouse hepatic triacyglycerol lipase (HL) were isolated from a mouse liver cDNA library with a human HL cDNA as a probe. The cloned HL cDNA of 1652 nucleotides predicts a mature protein of 488 amino acids preceded by a signal peptide of 22 amino acids. Two potential sites for N-glycosylation are identified, which are both conserved in rat and human HL. Combined lipase deficiency (cld) is a recessive mutation in mice, which causes the functional deficiency of HL and lipoprotein lipase. the isolated cDNA was used to study the expression of HL gene in cld/cld mice. Northern blot analysis of total cellular RNA from livers of cld/cld and normal mice showed that there are two mRNA species for HL with the sizes of 1.8 and 1.9 kilobases in both groups. However, the mRNA for HL was more abundant in cld/cld than in normal mice. RNase A protection assay of HL mRNA suggested that the multiple mRNA species for HL in cld/cld and normal mice are generated by differential utilization of polyadenylation signals and that there is no mutation in the structural gene for HL in cld/cld mice. The present study supports our hypothesis that the defect of HL activity in cld/cld mice is caused by abnormal post translational modification or processing of the lipase. C1 NIDDK,CELLULAR & DEV BIOL LAB,ENDOCRINOL SECT,BETHESDA,MD. MEDLANTIC RES FDN,MOLEC GENET LAB,WASHINGTON,DC. NR 42 TC 17 Z9 18 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 MAY 2 PY 1991 VL 1089 IS 1 BP 13 EP 20 DI 10.1016/0167-4781(91)90078-Z PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FN369 UT WOS:A1991FN36900003 PM 2025643 ER PT J AU MANDERSCHEID, RW AF MANDERSCHEID, RW TI STATISTICAL RESEARCH ACTIVITIES SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article RP MANDERSCHEID, RW (reprint author), NIMH,DIV BIOMETRY & APPL SCI,SURVEY & REPORTS BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD MAY PY 1991 VL 18 IS 5 BP 381 EP 384 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA FT171 UT WOS:A1991FT17100008 ER PT J AU AGRAWAL, S SARIN, PS AF AGRAWAL, S SARIN, PS TI ANTISENSE OLIGONUCLEOTIDES - GENE-REGULATION AND CHEMOTHERAPY OF AIDS SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Article DE ANTISENSE OLIGONUCLEOTIDE; HUMAN IMMUNODEFICIENCY VIRUS; CHEMOTHERAPY OF AIDS; PHOSPHOROTHIOATE; METHYLPHOSPHONATE; PHOSPHORAMIDATE; INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONICALLY INFECTED-CELLS; NUCLEOSIDE H-PHOSPHONATES; NUCLEIC-ACID CHEMISTRY; MATAGEN MASKING TAPE; MESSENGER-RNA; PHOSPHOROTHIOATE ANALOGS; ALKYL PHOSPHOTRIESTERS; CHEMICAL SYNTHESIS; ANTIVIRAL ACTIVITY AB The use of antisense oligonucleotides in control of gene regulation and inhibition of virus replication is a unique approach designed to interfere with cell and virus replication, transcription and translation machinery at the molecular level. Extensive studies ave been carried out to regulate replication of human immunodeficiency virus by synthetic oligonucleotides and their several sugar phosphate backbone modified analogues. Thus far, studies have been carried out in tissue culture, and inhibition of HIV expression has been monitored by several parameters. Oligonucleotide phosphorothioates are effective in inhibiting HIV expression in tissue culture at a concentration of 1.10(-7) M, which translates into a dose of approximately 0.6 mg/kg bodyweight. A non-toxic dose of 100 mg/kg, in preliminary acute toxicity experiments, represents an exploitable therapeutic window for 'oligonucleotide therapy'. C1 WORCESTER FDN EXPTL BIOL INC,SHREWSBURY,MA 01545. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 81 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY-JUN PY 1991 VL 6 IS 3 BP 251 EP 270 DI 10.1016/0169-409X(91)90020-D PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GF478 UT WOS:A1991GF47800003 ER PT J AU HEYES, MP LACKNER, A KAUFMAN, S MILSTIEN, S AF HEYES, MP LACKNER, A KAUFMAN, S MILSTIEN, S TI CEREBROSPINAL-FLUID AND SERUM NEOPTERIN AND BIOPTERIN IN D-RETROVIRUS-INFECTED RHESUS MACAQUES (MACACA-MULATTA) - RELATIONSHIP TO CLINICAL AND VIRAL STATUS SO AIDS LA English DT Article DE PTERINS; GAMMA-INTERFERON; GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE-I; AIDS; RETROVIRUS; CENTRAL NERVOUS SYSTEM ID INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY; QUINOLINIC ACID CONCENTRATIONS; CENTRAL NERVOUS-SYSTEM; INTERFERON-GAMMA; HUMAN-CELLS; TETRAHYDROBIOPTERIN BIOSYNTHESIS; PARALLEL INDUCTION; URINARY NEOPTERIN; TOXOPLASMA-GONDII; HUMAN-FIBROBLASTS AB Increases in serum and cerebrospinal fluid (CSF) neopterin concentrations accompany many inflammatory diseases, including infection with HIV-1 and may reflect activation of guanosine triphosphate (GTP) cyclohydrolase I by gamma-interferon and other cytokines. In the present study, macaques with clinical simian AIDS (SAIDS) infected with the immunosuppressive type-D retrovirus D/1/California had increased concentrations of CSF neopterin but not of biopterin beginning soon after seroconversion. Normal neopterin concentrations in the CSF were found in macaques with SAIDS-related complex as well as asymptomatic, viremic macaques. CSF biopterin, serum neopterin and serum biopterin concentrations of D/1/California-infected macaques were not different from the levels in control animals. The increase in CSF neopterin may reflect local inflammatory responses and paralleled previously documented changes in L-tryptophan metabolism in these macaques. However, the absence of macrophage infiltrates in the brain of the infected macaques suggests a non-macrophage source of both increased CSF neopterin and tryptophan metabolites in the SAIDS macaques. C1 NIMH, NEUROCHEM LAB, BETHESDA, MD 20892 USA. UNIV CALIF DAVIS, CALIF PRIMATE RES CTR, DAVIS, CA 95616 USA. RP NIMH, CLIN SCI LAB, ANALYT BIOCHEM SECT, BLDG 10, ROOM 3D40, BETHESDA, MD 20892 USA. FU NCRR NIH HHS [RR00169, RR00039]; NIAID NIH HHS [AI20573] NR 42 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD MAY PY 1991 VL 5 IS 5 BP 555 EP 560 DI 10.1097/00002030-199105000-00012 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA FR017 UT WOS:A1991FR01700012 PM 1863408 ER PT J AU NELSON, AM HASSIG, SE KAYEMBE, M OKONDA, L MULANGA, K BROWN, C KAYEMBE, K KALENGAYI, MM MULLICK, FG AF NELSON, AM HASSIG, SE KAYEMBE, M OKONDA, L MULANGA, K BROWN, C KAYEMBE, K KALENGAYI, MM MULLICK, FG TI HIV-1 SEROPOSITIVITY AND MORTALITY AT UNIVERSITY HOSPITAL, KINSHASA, ZAIRE, 1987 SO AIDS LA English DT Note DE HIV-1 SEROPREVALENCE; AIDS; AFRICA; MORTALITY ID AFRICAN CITY; AIDS; ADULT AB This study examines the impact of HIV-1 infection and AIDS on 500 of 563 consecutive deaths at University Hospital, Kinshasa, Zaire, in late 1987. HIV-1 seroprevalence was 31% for the entire population and 43% for the 247 adults. Forty-two (38%) of the 110 HIV-1-seropositive adult deaths occurred in those between the ages of 25 and 34 years. The mean age of death for seropositives was 36 years, 7.5 years less than seronegative deaths. AIDS and AIDS-associated diagnoses such as cryptococcal meningitis, chronic diarrhea and pneumonia accounted for 42% of all adult deaths and 74% of all HIV-1-seropositive adult deaths. Seventeen per cent of 50 sera initially negative by enzyme-linked immunosorbent assay (ELISA) were ultimately found to be HIV-1-seropositive by Western blot or p24 antigen testing. The data indicate that HIV-1 infection and AIDS contribute significantly to adult mortality in Kinshasa population and that sensitivity of ELISA tests decreases in terminal HIV-1 infection. C1 ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. PROJECT SIDA,KINSHASA,ZAIRE. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70118. UNIV HOSP KINSHASA,KINSHASA,ZAIRE. NIH,BETHESDA,MD 20892. NR 10 TC 20 Z9 20 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 MAY PY 1991 VL 5 IS 5 BP 583 EP 586 DI 10.1097/00002030-199105000-00018 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA FR017 UT WOS:A1991FR01700018 PM 1907462 ER PT J AU ROSS, EK FUERST, TR ORENSTEIN, JM ONEILL, T MARTIN, MA VENKATESAN, S AF ROSS, EK FUERST, TR ORENSTEIN, JM ONEILL, T MARTIN, MA VENKATESAN, S TI MATURATION OF HUMAN-IMMUNODEFICIENCY-VIRUS PARTICLES ASSEMBLED FROM THE GAG PRECURSOR PROTEIN REQUIRES INSITU PROCESSING BY GAG POL PROTEASE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID RECOMBINANT VACCINIA VIRUS; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; SYNDROME RETROVIRUS; EXPRESSION VECTOR; HTLV-III; HIV-1; CELLS; TYPE-1; IDENTIFICATION AB The vaccinia virus expression system was used to determine the role of human immunodeficiency virus type 1 (HIV-1) protease in viral morphogenesis and maturation. The unprocessed p55 gag precursor polyprotein alone was assembled to form HIV-1 particles which budded from cells. The particles were spherical and immature, containing an electron-dense shell in the particle submembrane; there was no evidence of core formation. Expression of both gag and pol proteins from a recombinant containing the complete gag-pol coding sequences resulted in intracellular processing of gag-pol proteins and the production of mature particles with electrondense cores characteristic of wild-type HIV virions. To ascertain the role of protein processing in particle maturation, the pol ORF in the gag-pol recombinant was truncated to limit expression of the pol gene to the protease domain. With this recombinant expressing p55 gag and protease, intracellular processing was observed. Some of the resultant particles were partially mature and contained processed gag protein subunits. In contrast, particle maturation was not observed when the HIV-1 protease and p55 gag were coexpressed from separate recombinants, despite evidence of intracellular gag processing. These findings suggest that HIV-1 protease must be an integral component of the full-length gag-pol precursor for optimal processing and virion maturation. C1 NIAID,MED MICROBIOL LAB,ROOM 36,BLDG 4,BETHESDA,MD 20892. MOLEC VACCINES INC,GAITHERSBURG,MD. GEORGE WASHINGTON UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20052. NR 34 TC 30 Z9 30 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 MAY PY 1991 VL 7 IS 5 BP 475 EP 483 DI 10.1089/aid.1991.7.475 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA FT600 UT WOS:A1991FT60000008 PM 1873082 ER PT J AU MICKISCH, G ALKEN, P GOTTESMAN, MM PASTAN, I AF MICKISCH, G ALKEN, P GOTTESMAN, MM PASTAN, I TI REVERSAL OF MULTIDRUG RESISTANCE IN HUMAN RENAL-CARCINOMA CELLS AND IN TRANSGENIC MICE THAT EXPRESS THE HUMAN MDR1 GENE USING NEW POTENT VERAPAMIL DERIVATIVES SO AKTUELLE UROLOGIE LA German DT Article DE HUMAN RENAL CELL CARCINOMA; MDR1 GENE; R-VERAPAMIL; MDR-TRANSGENIC MICE; CHEMOSENSITIZATION AB Multidrug resistance in human renal cell carcinoma is mainly caused by expression of the MDR1 gene and is characterized by a broad spectrum cross resistance to many natural product chemotherapeutic agents. This resistance can be overcome by applying chemosensitizers which inhibit the function of the MDR1 gene product P-glycoprotein. The development of new reversing agents with fewer side effects and a higher potency in modifying resistance is a high priority of research on drug resistance. We have evaluated 4 new verapamil derivatives on 21 primary human renal cell carcinomas in vitro, and also tested them in an MDR-transgenic mice model. These mice express the human MDR1 gene in their bone marrow cells and measurement of their white blood counts provides a simple, rapid and reliable system to screen for the potency of MDR-reversing agents in vivo. We demonstrate here that all 4 drugs are effective in reversing multidrug resistance in primary cultures of human renal cell carcinomas when used in combination with vinblastine chemotherapy, and to a lesser extent with doxorubicin or daunomycin chemotherapy. Our in vivo data indicate that two of these reversing agents display low toxicity at high concentrations and are more effective at low, clinically achievable concentrations, than the other two drugs and R-verapamil. These results make the two drugs attractive candidates to be taken into clinical trials. RP MICKISCH, G (reprint author), NCI,MOLEC BIOL LAB,BLDG 37,ROOM 2D27,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0001-7868 J9 AKTUEL UROL JI Aktuelle Urol. PD MAY PY 1991 VL 22 IS 3 BP 125 EP 131 DI 10.1055/s-2008-1060490 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA FT458 UT WOS:A1991FT45800001 ER PT J AU COHEN, SG DUNN, LM AF COHEN, SG DUNN, LM TI LANDMARK COMMENTARY - THE LYMPHOCYTOLOGISTS - ABELL AND SCHENCK ON ANAPHYLAXIS SO ALLERGY PROCEEDINGS LA English DT Article RP COHEN, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD MAY-JUN PY 1991 VL 12 IS 3 BP 199 EP 205 DI 10.2500/108854191778879412 PG 7 WC Allergy SC Allergy GA FW797 UT WOS:A1991FW79700015 PM 1894139 ER PT J AU LONGNECKER, MP TAYLOR, PR LEVANDER, OA HOWE, SM VEILLON, C MCADAM, PA PATTERSON, KY HOLDEN, JM STAMPFER, MJ MORRIS, JS WILLETT, WC AF LONGNECKER, MP TAYLOR, PR LEVANDER, OA HOWE, SM VEILLON, C MCADAM, PA PATTERSON, KY HOLDEN, JM STAMPFER, MJ MORRIS, JS WILLETT, WC TI SELENIUM IN DIET, BLOOD, AND TOENAILS IN RELATION TO HUMAN HEALTH IN A SELENIFEROUS AREA SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE SELENIUM; TOXICITY; HUMANS ID NUTRITIONAL AVAILABILITY; UNITED-STATES; CHINA; INTOXICATION; FOODS; RATS AB To determine whether high dietary selenium intake was associated with adverse effects, selenium in diet, blood, and toenails was studied in relation to human health in adults residing in western South Dakota and eastern Wyoming. Over a 2-y period 142 subjects were recruited from households selected at random and from ranches where unusually high selenium intakes were suspected. Subjects completed health questionnaires, underwent physical examinations, provided blood samples for clinical assessment, and provided blood, urine, toenails, and duplicate-plate food collections for selenium analysis. About half of the 142 free-living subjects had selenium intakes > 2.54 mu-mol/d (200-mu-g/d) (range 0.86-9.20-mu-mol/d, or 68-724-mu-g/d). Physical findings characteristic of selenium toxicity were not present nor were clinically significant changes in laboratory tests or frequency of symptoms related to selenium in the blood, toenails, or diet. We found no evidence of toxicity from selenium in subjects whose intake was as high as 9.20-mu-mol/d (724-mu-g/d). C1 UNIV MISSOURI,RES REACTOR FACIL,COLUMBIA,MO 65201. NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. USDA,VIT & MINERAL NUTR LAB,BELTSVILLE,MD 20705. USDA,NUTRIENT COMPOSIT LAB,BELTSVILLE,MD 20705. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. S DAKOTA SCH MINES & TECHNOL,RAPID CITY,SD 57701. RP LONGNECKER, MP (reprint author), UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,10833 LE CONTE AVE,LOS ANGELES,CA 90024, USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 32 TC 125 Z9 129 U1 2 U2 4 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1991 VL 53 IS 5 BP 1288 EP 1294 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FJ408 UT WOS:A1991FJ40800032 PM 2021136 ER PT J AU MAVALANKAR, DV GRAY, RH AF MAVALANKAR, DV GRAY, RH TI INTERPREGNANCY INTERVAL AND RISK OF PRETERM LABOR SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID LOW-BIRTH-WEIGHT; GESTATIONAL-AGE C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT POPULAT DYNAM,BALTIMORE,MD 21205. RP MAVALANKAR, DV (reprint author), NICHHD,DIV PREVENT RES,EXECUT PLAZA N,RM 640,BETHESDA,MD 20892, USA. NR 8 TC 8 Z9 8 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 1991 VL 133 IS 9 BP 958 EP 959 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FM760 UT WOS:A1991FM76000012 PM 2028982 ER PT J AU MORENOOTERO, R GARCIAMONZON, C GARCIASANCHEZ, A BUEY, LG PAJARES, JM DIBISCEGLIE, AM AF MORENOOTERO, R GARCIAMONZON, C GARCIASANCHEZ, A BUEY, LG PAJARES, JM DIBISCEGLIE, AM TI DEVELOPMENT OF CIRRHOSIS AFTER CHRONIC TYPE-B HEPATITIS - A CLINICOPATHOLOGICAL AND FOLLOW-UP-STUDY OF 46 HBEAG-POSITIVE ASYMPTOMATIC PATIENTS SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CHRONIC ACTIVE HEPATITIS; VIRUS-INFECTION; ANTI-HBE; DNA-POLYMERASE; HBSAG-CARRIERS; SEROCONVERSION; LIVER; SERUM; REPLICATION; THERAPY AB The rate of HBeAg clearance and the outcome were analyzed in 46 patients with asymptomatic chronic hepatitis B virus (HBV) infection whose condition was followed for 1-4 yr (mean 2.4). Mean age was 32.5 yr (range 10-68), and 28 (61%) were males. All had chronic hepatitis, on biopsy, and were positive for HBcAg on hepatocytes. Alcoholics, homosexuals, drug abusers, immunocompromised patients, and those with advanced liver disease were excluded. During the follow-up, 25 patients (54%) cleared HBeAg and became seronegative for HBV-DNAp. The estimated annual rate of seroconversion was 26%. One patient cleared HBsAg. After seroconversion, 18 patients had no evidence of ongoing liver disease, proved by biopsy in eight and by clinical follow-up in 10 that refused biopsy. A second liver biopsy was available in 15 patients, and HBcAg was negative in all; histology was normal in eight, unchanged in one, and compatible with cirrhosis in six. All six had clinical and/or biochemical evidence of advanced liver disease. These were significantly older at the start of the study, and had chronic active heptatitis with bridging necrosis on initial biopsy. Early identification of patients with silent chronic HBV infection and high levels of viral replication for antiviral therapy could prevent transmission of the infection and stop progression to liver cirrhosis and hepatocellular carcinoma. C1 UNIV AUTONOMA MADRID,HOSP PRINCESA,PATHOL SERV,E-28006 MADRID,SPAIN. NIDDK,LIVER DIS SECT,BETHESDA,MD. RP MORENOOTERO, R (reprint author), UNIV AUTONOMA MADRID,HOSP PRINCESA,GASTROENTEROL SERV,LIVER UNIT,PLANTA 3,DIEGO LEON 62,E-28006 MADRID,SPAIN. NR 26 TC 25 Z9 25 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 1991 VL 86 IS 5 BP 560 EP 564 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA FL923 UT WOS:A1991FL92300006 PM 2028945 ER PT J AU MULLEN, KD HOOFNAGLE, JH JONES, EA AF MULLEN, KD HOOFNAGLE, JH JONES, EA TI SHOCK WAVE-INDUCED PANCREATIC TRAUMA SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Note ID LITHOTRIPSY ESWL; STONES; FRAGMENTATION; EXPERIENCE; CALCULI; DISEASE AB A case is described of the appearance of a pancreatic or peripancreatic lesion after left renal calculus fragmentation by extracorporeal shock wave lithotripsy (ESWL). Its anatomical location and subsequent disappearance suggest it was related to trauma caused by the shock waves. The brief literature on pancreatic injury afer ESWL is reviewed, and the role of the patient's underlying liver disease in the genesis of this complication is discussed. C1 METROHLTH MED CTR,DEPT MED,DIV GASTROENTEROL,CLEVELAND,OH. RP JONES, EA (reprint author), NIDDK,LIVER DIS SECT,BETHESDA,MD 20892, USA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 1991 VL 86 IS 5 BP 630 EP 632 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA FL923 UT WOS:A1991FL92300023 PM 2028959 ER PT J AU GARTY, H FURLONG, TJ ELLIS, DE SPRING, KR AF GARTY, H FURLONG, TJ ELLIS, DE SPRING, KR TI SORBITOL PERMEASE - AN APICAL MEMBRANE TRANSPORTER IN CULTURED RENAL PAPILLARY EPITHELIAL-CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PAP-HT25; CELL VOLUME; PLASMA MEMBRANE VESICLES; REGULATORY VOLUME DECREASE; QUINIDINE; HYPOTONICITY ID ACTIVE ORGANIC SOLUTES; VOLUME REGULATION; ALDOSE REDUCTASE; BINDING; SODIUM; DRUGS; NACL AB The efflux of sorbitol from the rabbit papillary epithelial cell line PAP-HT25 occurs through a specific transport pathway, which we denote the "sorbitol permease." The permease was studied by measuring cell volume changes that accompanied osmotic swelling and by determination of the sorbitol efflux from plasma membrane vesicles. The cell volume studies showed that sorbitol efflux in response to hypotonicity occurred only across the apical membrane of the cells and that loss of sorbitol was the primary mechanism for regulatory volume decrease (RVD) by these cells. Quinidine, a permeant inhibitor of the sorbitol permease, was shown to prevent RVD when added to either apical or basolateral bathing solution. Cell volume experiments also showed that the permease was present only on the apical membrane of cells that had been grown in isotonic medium and did not accumulate sorbitol. The permease could be demonstrated in membrane vesicles obtained from cells exposed to a hypotonic environment before being homogenized. Quinidine blocked the sorbitol efflux from vesicles indicating that it either directly inhibited the permease or a membrane-associated activation step. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N307,BETHESDA,MD 20892. NR 18 TC 44 Z9 45 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1991 VL 260 IS 5 BP F650 EP F656 PN 2 PG 7 WC Physiology SC Physiology GA FM778 UT WOS:A1991FM77800079 PM 2035652 ER PT J AU WALL, SM FLESSNER, MF KNEPPER, MA AF WALL, SM FLESSNER, MF KNEPPER, MA TI DISTRIBUTION OF LUMINAL CARBONIC-ANHYDRASE ACTIVITY ALONG RAT INNER MEDULLARY COLLECTING DUCT SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE DISEQUILIBRIUM PH; AMMONIUM; BICARBONATE; KIDNEY ID BICARBONATE TRANSPORT; DISEQUILIBRIUM PH; AMMONIA TRANSPORT; KIDNEY; SECRETION; PURIFICATION; TUBULES; CELLS; IV AB The isolated perfused tubule technique was utilized to determine whether endogenous luminal carbonic anhydrase is present in the initial or terminal parts of the inner medullary collecting duct (IMCD) of the rat. This was accomplished by measuring the luminal disequilibrium pH in the presence of a large luminal proton source created by perfusing the lumen with a solution containing 10 mM NH4Cl. (NH3 efflux causes H+ to be released from NH4+ in the lumen). The disequilibrium pH was calculated by subtracting the equilibrium pH from the measured pH at the end of the tubule lumen. The end-luminal equilibrium pH was calculated from the total CO2 concentration in the collected fluid, as measured by microcalorimetry. The end-luminal pH was determined by measuring the fluorescent signal from the the pH-sensitive dye 2', 7' -bis(2-carboxyethyl) -5(6)-carboxyfluorescein (BCECF), which was added to the luminal perfusate in its nonesterified form. In the initial IMCD, there was no measurable disequilibrium pH. With the addition of the carbonic anhydrase inhibitor acetazolamide to the luminal fluid, a significant acidic pH disequilibrium was elicited. In the terminal IMCD under control conditions a statistically significant acidic disequilibrium pH was measured. The disequilibrium was obliterated when exogenous carbonic anhydrase was added to the luminal perfusate. These findings were verified by measuring total ammonia flux by ultramicrofluorometry. The results demonstrate endogenous luminal carbonic anhydrase activity in the initial IMCD but a lack of enzyme activity in the terminal IMCD. C1 NHLBI,DIV HEART & VASC DIS,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N307,BETHESDA,MD 20892. NR 28 TC 26 Z9 26 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1991 VL 260 IS 5 BP F738 EP F748 PN 2 PG 11 WC Physiology SC Physiology GA FM778 UT WOS:A1991FM77800090 PM 1903600 ER PT J AU SEVERI, C JENSEN, RT ERSPAMER, V DARPINO, L COY, DH TORSOLI, A DELLEFAVE, G AF SEVERI, C JENSEN, RT ERSPAMER, V DARPINO, L COY, DH TORSOLI, A DELLEFAVE, G TI DIFFERENT RECEPTORS MEDIATE THE ACTION OF BOMBESIN-RELATED PEPTIDES ON GASTRIC SMOOTH-MUSCLE CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GASTRIN-RELEASING PEPTIDE; NEUROMEDIN-B; ISOLATED SMOOTH MUSCLE CELLS; BOMBESIN RECEPTOR SUBTYPES ID PORCINE SPINAL-CORD; GASTROINTESTINAL-TRACT; BINDING-SITES; NEUROMEDIN-B; CHOLECYSTOKININ; IDENTIFICATION; ANTAGONISTS; GALLBLADDER; TACHYKININS; INTESTINE AB Recent studies suggest that different subtypes of receptors may mediate the action of various bombesin-related peptides in different tissues. In the present study the ability of bombesin and its structurally related peptides {litorin, gastrin-releasing peptide (GRP), GRP18-27, neuromedin B, [Leu8]litorin, and bombesin nonapeptide BN(6-14)} to interact with smooth muscle cells isolated from guinea pig stomach was investigated. Each peptide induced a specific contractile response with potencies (D50 in pM) of [Leu8]litorin (0.7) > bombesin (1.2) > litorin (3) > neuromedin B (3.5) = GRP (3.8) = GRP18-27 (3.9) > BN(6-14) (70.9). The specific bombesin receptor antagonist psi-13,14-bombesin differed in its potency for inhibiting equipotent concentrations of bombesin, GRP, or neuromedin B, was equipotent for bombesin or GRP (IC50 12.7 and 22.1 nM), and was 11 times less potent for neuromedin B (IC50 234.5 nM), suggesting the presence of subtypes of receptors mediating the action of bombesin-related peptides. To further investigate this possibility, a technique of receptor protection that enables selective preservation of one receptor type was used. GRP or bombesin protected completely the response to GRP or bombesin but abolished the subsequent contractile response to neuromedin B. Neuromedin B, instead, protected only the response to neuromedin B. These results demonstrate that gastric smooth muscle cells possess specific receptors that interact with bombesin-related peptides and that two receptor subtypes mediate the contractile response to these peptides: one subtype is selective for bombesin or GRP, the other for neuromedin B. C1 UNIV LA SAPIENZA,GASTROENTEROL UNIT,I-00161 ROME,ITALY. UNIV LA SAPIENZA,PHARMACOL UNIT,I-00161 ROME,ITALY. NIDDKD,BETHESDA,MD 20892. TULANE UNIV,MED CTR,DEPT MED,PEPTIDE RES LABS,NEW ORLEANS,LA 70012. NR 32 TC 60 Z9 60 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1991 VL 260 IS 5 BP G683 EP G690 PN 1 PG 8 WC Physiology SC Physiology GA FM776 UT WOS:A1991FM77600050 PM 1852115 ER PT J AU SWAIN, JA MCDONALD, TJ ROBBINS, RC BALABAN, RS AF SWAIN, JA MCDONALD, TJ ROBBINS, RC BALABAN, RS TI RELATIONSHIP OF CEREBRAL AND MYOCARDIAL INTRACELLULAR PH TO BLOOD-PH DURING HYPOTHERMIA SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE P-31 NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; CARDIOPULMONARY BYPASS; CEREBRAL METABOLISM; MYOCARDIAL METABOLISM; BRAIN; HEART ID MAGNETIC-RESONANCE; BRAIN; HEART; FIBRILLATION; METABOLISM AB The regulation of tissue pH during hypothermia is important for cellular homeostasis. The present study was undertaken to determine the relationship between blood pH and intracellular pH in the brain and heart during hypothermia in sheep and to compare these data with those in humans. Intracellular pH (pH(i) was determined by P-31 nuclear magnetic resonance (NMR) spectroscopic data collected from the heart and brain of sheep during cardiopulmonary bypass (CPB). Alpha-stat and pH-stat blood pH management schemes were compared. When the blood pH was held constant (pH stat), the pH(i) of the heart increased from 7.01 +/- 0.01 at 37-degrees-C to 7.18 +/- 0.02 at 26-degrees-C, and the pH(i) of the brain increased from 7.04 +/- 0.02 at 37-degrees-C to 7.23 +/- 0.02 at 26-degrees-C and to 7.32 +/- 0.04 at 20-degrees-C. Alpha-stat pH management resulted in similar increases in pH to that found with pH-stat [heart: 7.00 +/- 0.02 at 37-degrees-C to 7.19 +/- 0.03 at 26-degrees-C; brain: 7.07 +/- 0.02 at 37-degrees-C to 7.29 +/- 0.02 at 26-degrees-C, and 7.32 +/- 0.03 at 20-degrees-C]. The tissue pH of the heart in humans showed similar findings during blood pH-stat regulation. This study revealed that both the brain and heart pH(i) in heterotherms are regulated independently of blood pH, following alpha-stat principles, and thus maintain a pH gradient between the blood and tissues during hypothermia despite wide variations of blood pH. Therefore, known variations in brain and heart function between blood pH management schemes cannot be explained on the basis of tissue pH(i). C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. NR 26 TC 30 Z9 30 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1991 VL 260 IS 5 BP H1640 EP H1644 PN 2 PG 5 WC Physiology SC Physiology GA FM778 UT WOS:A1991FM77800033 ER PT J AU UNGER, EF SHEFFIELD, CD EPSTEIN, SE AF UNGER, EF SHEFFIELD, CD EPSTEIN, SE TI HEPARIN PROMOTES THE FORMATION OF EXTRACARDIAC TO CORONARY ANASTOMOSES IN A CANINE MODEL SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE NEOVASCULARIZATION; CORONARY CIRCULATION; COLLATERAL CIRCULATION; MYOCARDIAL ISCHEMIA ID FIBROBLAST GROWTH-FACTOR; ENDOTHELIAL-CELLS-INVITRO; BLOOD-FLOW MEASUREMENTS; PURIFICATION; INVIVO; LOCALIZATION; CIRCULATION; REPAIR; BINDS; HEART AB We developed a canine model for the in vivo utilization of angiogenesis factors to promote revascularization of a collateral-dependent area of the heart and assessed the potential of heparin in this preparation. Ameroids were placed on the proximal left anterior descending coronary artery (LAD) of 29 dogs, and the left internal mammary artery (IMA) was implanted in an intramyocardial tunnel in proximity to the LAD. A tube positioned in the distal IMA provided a continuous retrograde infusion directly into the vessel from an implanted pump. Heparin (15 or 150 U/h) or saline vehicle was infused. After 8 wk, regional myocardial blood flow was assessed in the anesthetized state during adenosine-induced vasodilatation, before and during occlusion of the IMA. The IMA provided a greater proportion of maximal collateral flow in heparin-treated dogs (22 +/- 5%, n = 17) than in saline-treated dogs (9 +/- 2%, n = 12, P < 0.05). Thus continuous infusion of heparin promotes the formation of collaterals between the extracardiac artery and the myocardial circulation, establishing the feasibility of targeting angiogenic agents for myocardial revascularization. RP UNGER, EF (reprint author), NHLBI,CARDIOL BRANCH,EXPTL PHYSIOL & PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 35 TC 66 Z9 66 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1991 VL 260 IS 5 BP H1625 EP H1634 PN 2 PG 10 WC Physiology SC Physiology GA FM778 UT WOS:A1991FM77800031 ER PT J AU GROSSMAN, E CHANG, PC HOFFMAN, A TAMRAT, M KOPIN, IJ GOLDSTEIN, DS AF GROSSMAN, E CHANG, PC HOFFMAN, A TAMRAT, M KOPIN, IJ GOLDSTEIN, DS TI TRACER NOREPINEPHRINE KINETICS - DEPENDENCE ON REGIONAL BLOOD-FLOW AND THE SITE OF INFUSION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SYMPATHETIC NERVOUS SYSTEM; ISOPROTERENOL ID PLASMA NORADRENALINE; NERVE ACTIVITY; RELEASE; CATECHOLAMINES; EPINEPHRINE; FOREARM; REMOVAL; HUMANS; HEART; ASSAY AB The rate of appearance of the sympathetic neurotransmitter norepinephrine (NE) in the regional venous drainage (NE spillover) can be estimated based on intravenous or intra-arterial infusions of [H-3]NE. The present study examined whether forearm NE spillover (FASO) in humans depends on forearm blood flow (FBF) and on the site of infusion of the tracer. Healthy volunteers underwent infusions of [H-e]NE and [H-3]isoproterenol (Iso) administered intravenously (n = 21), intra-arterially (n = 32), or by both routes in the same experimental session (n = 7). FBF was manipulated by intra-arterial infusions of the vasodilator sodium nitroprusside (n = 7) or the vasoconstrictor methoxamine (n = 7). Forearm extraction percents of [H-3]NE exceeded those of [H-e]Iso in all subjects undergoing intravenous infusions (54 vs. 46%, P < 0.001), whereas extraction percents of [H-3]Iso exceeded those of [H-3]NE when the tracers were infused intra-arterially. Regardless of the infusion site, FASO was positively correlated with FBF (r = 0.44, P < 0.005). Nitroprusside increased FBF and FASO, and methoxamine decreased FBF and FASO. When the tracers were added to whole blood, 89% of [H-3]NE and 83% of [H-3]Iso remained in plasma after 1 min; although no further loss of [H-3]NE occurred over time, only 60% of the added [H-3]Iso remained in plasma by 20 min. The results indicate that regional NE spillover is flow dependent, complicating inferences about regional sympathoneural activity. Intra-arterial infusion of [H-3]NE results in higher estimates of regional NE spillover than does intravenous infusion of the tracer. [H-3]NE and [H-3]Iso bind rapidly and differently to nonplasma components of blood, invalidating the use of the dual tracer approach to estimate regional neuronal uptake of NE when the tracers are administered intra-arterially. C1 NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N214,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 20 TC 44 Z9 44 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD MAY PY 1991 VL 260 IS 5 BP R946 EP R952 PN 2 PG 7 WC Physiology SC Physiology GA FM778 UT WOS:A1991FM77800064 PM 2035707 ER PT J AU ZORC, JJ LARSON, DB LYONS, JS BEARDSLEY, RS AF ZORC, JJ LARSON, DB LYONS, JS BEARDSLEY, RS TI EXPENDITURES FOR PSYCHOTROPIC MEDICATIONS IN THE UNITED-STATES IN 1985 SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CARE AB Objective: Psychotropic medications have seldom been included in estimates of the costs of mental health services. In the infrequent case that these costs have been assessed, they have been estimated by using national surveys of consumers of health services. The objective of this study was to estimate the costs of prescriptions for psychotropic medications in the United States in 1985 and to assess the difference with the most recent cost estimate from a health services survey (1977). Method: Study data were based on retail costs of psychotropic medications reported to the Pharmaceutical Data Service Alpha National Prescription and Sales Audit. The data come from a computerized survey panel of 2,250 pharmacies representative of the more than 14,000 pharmacies nationwide. The database includes all medication prescriptions filled, whether paid with cash or Medicaid or reimbursed by third-party payment. Analyses were limited to psychotropic medication prescriptions. Results: In 1985, $1.45 billion was spent on outpatient psychotropic medications. Nearly $868 million (60% of the total) was spent on antianxiety and sedative-hypnotic medications, while approximately $263 million (18%) was spent on antipsychotic medications, $240 million (17%) on antidepressants, and $84 million (5%) on combination psychotropic medications. These expenditures were much higher than would have been expected given the most recent health services estimate of $513 million. Conclusions: These results demonstrate the substantial cost of psychotropic medications in 1985. The finding that the cost of psychotropic medications was so high, in contrast to the lower estimate from the 1977 survey, demonstrates the importance of obtaining more frequent cost estimates and basing future estimates on medication databases. C1 NIMH,RM 18C-14,5600 FISHERS LANE,ROCKVILLE,MD 20857. COLUMBIA UNIV,NEW YORK,NY 10027. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. UNIV MARYLAND,BALTIMORE,MD 21201. NR 16 TC 8 Z9 8 U1 0 U2 0 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 MAY PY 1991 VL 148 IS 5 BP 644 EP 647 PG 4 WC Psychiatry SC Psychiatry GA FJ317 UT WOS:A1991FJ31700015 PM 2018168 ER PT J AU KHOT, V WYATT, RJ AF KHOT, V WYATT, RJ TI NOT ALL THAT MOVES IS TARDIVE-DYSKINESIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ABNORMAL INVOLUNTARY MOVEMENTS; RISK-FACTORS; FOLLOW-UP; PREVALENCE; SCHIZOPHRENICS AB Objective: Because tardive dyskinesia and spontaneous dyskinesia appear the same, it is difficult to determine whether an individual patient's abnormal movements are induced by medication or have developed spontaneously. Therefore, estimates of the prevalence of tardive dyskinesia that are based on observations not adjusted for spontaneous dyskinesia are inflated. In addition, age is thought to be an important risk factor in the development of both tardive and spontaneous dyskinesias. The authors estimate the prevalence of both disorders for specific age groups. Method: The authors reviewed nine reports on dyskinesia prevalence that included history of neuroleptic treatment and related prevalence to age. A rating of 2 or more on the Abnormal Involuntary Movement Scale or an equivalent score on another scale was considered an indication of dyskinesia. If the subject had taken neuroleptics for more than 3 months, the movement disorder was classified as neuroleptic-associated dyskinesia; other dyskinesias were considered spontaneous. The prevalence of tardive dyskinesia was defined as the rate of neuroleptic-associated dyskinesia minus the rate of spontaneous dyskinesia. Results: The true rate of tardive dyskinesia was below 20% for all age groups except 70-79 years. The correlation between the rate of neuroleptic-associated dyskinesia and the rate of spontaneous dyskinesia was low. Conclusions: After age 40 the prevalence of spontaneous dyskinesia is sufficiently high to conclude that many patients with diagnoses of tardive dyskinesia have abnormal movements attributable to causes other than neuroleptics. C1 NIMH,NEUROPSYCHIAT BRANCH,BETHESDA,MD 20892. NR 32 TC 57 Z9 57 U1 0 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 MAY PY 1991 VL 148 IS 5 BP 661 EP 666 PG 6 WC Psychiatry SC Psychiatry GA FJ317 UT WOS:A1991FJ31700019 PM 1673323 ER PT J AU LANE, HC HOLMBERG, SD JAFFE, HW AF LANE, HC HOLMBERG, SD JAFFE, HW TI HIV SEROCONVERSION AND ORAL INTERCOURSE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID HUMAN IMMUNODEFICIENCY VIRUS; MEN C1 CTR DIS CONTROL,CTR INFECT DIS,DIV HIV AIDS,ATLANTA,GA 30333. RP LANE, HC (reprint author), NIAID,BLDG 10,ROOM 11B09,BETHESDA,MD 20892, USA. NR 5 TC 31 Z9 31 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 1991 VL 81 IS 5 BP 658 EP 658 DI 10.2105/AJPH.81.5.658 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FU762 UT WOS:A1991FU76200027 PM 2014875 ER PT J AU KALTER, VG BRODY, AR AF KALTER, VG BRODY, AR TI RECEPTORS FOR TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) ON RAT LUNG FIBROBLASTS HAVE HIGHER AFFINITY FOR TGF-BETA-1 THAN FOR TGF-BETA-2 SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article AB Most cell types have receptors for transforming growth factor-beta (TGF-beta) and respond similarly to TGF-beta-1 and TGF-beta-2. We have demonstrated the presence of a single class of high-affinity receptors (approximately 10,000 sites/cell) for TGF-beta-1 (K(d) = 23 pM) and TGF-beta-2 (K(d) = 41 pM) on early-passage rat lung fibroblasts (RLF). Incubation with unlabeled TGF-beta-1 and TGF-beta-2 resulted in concentration-dependent inhibition of binding of 15 pM [I-125]TGF-beta-1 (ED50, 20 and 28 pM, respectively) and [I-125]TGF-beta-2 (ED50, 36 and 56 pM, respectively). TGF-beta receptors affinity-cross-linked with 100 pM [I-125]TGF-beta-1 or [I-125]TGF-beta-2 were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis and exhibited labeled protein bands of 68, 88, and 286 kD. Densitometric analysis of the resulting autoradiograms showed that the different molecular weight TGF-beta binding proteins exhibited separate affinities for the two forms of TGF-beta. Both TGF-beta-1 and TGF-beta-2 altered the morphology and cytoskeleton of RLF in a similar manner, but TGF-beta-1 was more potent than TGF-beta-2 in the inhibition of RLF growth and colony formation, with 50% inhibition by 0.12 pM TGF-beta-1 and 4.4 pM TGF-beta-2. Different affinities for the TGF-beta-s may indicate selectivity among the receptor subtypes with regard to the biologic responsiveness of RLF to TGF-beta-s. We believe this to be the first demonstration of biologically responsive TGF-beta receptors with different affinities for TGF-beta-1 and TGF-beta-2 on cells derived from normal, nonimmortal RLF. In establishing the basic mechanisms of pulmonary fibrosis, it will be essential to understand the biology and biochemistry of the receptors that may control cell division and production of extracellular matrix components by fibroblasts. C1 NIEHS, PULM PATHOBIOL LAB, POB 12233-D2-02, RES TRIANGLE PK, NC 27709 USA. NR 60 TC 22 Z9 22 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 1991 VL 4 IS 5 BP 397 EP 407 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA FK264 UT WOS:A1991FK26400003 PM 1850605 ER PT J AU SCHOOLER, C AF SCHOOLER, C TI CULTURE CONTROL AND COMMITMENT - A STUDY OF WORK ORGANIZATION AND WORK ATTITUDES IN THE UNITED-STATES AND JAPAN - LINCOLN,JR, KALLEBERG,AL SO AMERICAN JOURNAL OF SOCIOLOGY LA English DT Book Review RP SCHOOLER, C (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9602 J9 AM J SOCIOL JI Am. J. Sociol. PD MAY PY 1991 VL 96 IS 6 BP 1600 EP 1602 DI 10.1086/229729 PG 3 WC Sociology SC Sociology GA FM346 UT WOS:A1991FM34600043 ER PT J AU JAFFE, ES GONZALEZ, CL MEDEIROS, LJ RAFFELD, M AF JAFFE, ES GONZALEZ, CL MEDEIROS, LJ RAFFELD, M TI T-CELL RICH B-CELL LYMPHOMAS SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter RP JAFFE, ES (reprint author), NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892, USA. NR 7 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 1991 VL 15 IS 5 BP 491 EP 492 DI 10.1097/00000478-199105000-00010 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA FH203 UT WOS:A1991FH20300010 PM 1867707 ER PT J AU TSUNO, K MIURA, K TAKEYA, M KOLOBOW, T MORIOKA, T AF TSUNO, K MIURA, K TAKEYA, M KOLOBOW, T MORIOKA, T TI HISTOPATHOLOGIC PULMONARY CHANGES FROM MECHANICAL VENTILATION AT HIGH PEAK AIRWAY PRESSURES SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID END-EXPIRATORY PRESSURE; HIGH TIDAL VOLUME; LUNG; OXYGENATION; EDEMA AB We investigated the histopathologic pulmonary changes induced by mechanical pulmonary ventilation (MV) with a high peak airway pressure and a large tidal volume in healthy baby pigs. Eleven animals were mechanically ventilated at a peak inspiratory pressure (PIP) of 40 cm H2O, a respiratory rate (RR) of 20 min-1, a positive end-expiratory pressure (PEEP) of 3 to 5 cm H2O, and an FlO2 of 0.4. High airway pressure MV was terminated in 22 +/- 11 h because of severe hypoxemia in the animals. Five of the baby pigs were killed for gross and light microscope studies. The pulmonary changes consisted of alveolar hemorrhage, alveolar neutrophil infiltration, alveolar macrophage and type II pneumocyte proliferation, interstitial congestion and thickening, interstitial lymphocyte infiltration, emphysematous change, and hyaline membrane formation. Those lesions were similar to that seen in the early stage of the adult respiratory distress syndrome (ARDS). The remaining six animals were treated for 3 to 6 days with conventional respiratory care with appropriate ventilator settings. Prominent organized alveolar exudate in addition to lesions was also found in the five animals. These findings were indistinguishable from the clinical late stage of ARDS. Six control animals were mechanically ventilated at a PIP of less than 18 cm H2O, a RR of 20 min-1, a PEEP of 3 to 5 cm H2O, and an FlO2 of 0.4 for 48 h. They showed no notable changes in lung functions and histopathologic findings. Aggressive MV with a high PIP is often applied to patients with respiratory distress to attain adequate pulmonary gas exchange. Such treatment may affect the underlying disease process of the acute lung injury and may contribute to the specific lung pathology seen in ARDS. C1 KUMAMOTO UNIV,SCH MED,DEPT PATHOL 2,KUMAMOTO 860,JAPAN. KUMAMOTO CITY HOSP,DIV PATHOL,KUMAMOTO,JAPAN. NHLBI,BETHESDA,MD 20892. RP TSUNO, K (reprint author), KUMAMOTO UNIV,SCH MED,DEPT ANESTHESIOL,1-1-1 HONJYO,KUMAMOTO 860,JAPAN. NR 29 TC 195 Z9 201 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD MAY PY 1991 VL 143 IS 5 BP 1115 EP 1120 PG 6 WC Respiratory System SC Respiratory System GA FK720 UT WOS:A1991FK72000040 PM 2024823 ER PT J AU PIACENTINI, GL KALINER, MA AF PIACENTINI, GL KALINER, MA TI THE POTENTIAL ROLES OF LEUKOTRIENES IN BRONCHIAL-ASTHMA SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article; Proceedings Paper CT SYMP ON THE CLINICAL IMPORTANCE OF LEUKOTRIENES AND PLATELET-ACTIVATING FACTOR IN ALLERGIC RESPIRATORY DISEASES : THERAPEUTIC ADVANCES FOR TODAY CY NOV 14, 1990 CL SAN FRANCISCO, CA SP ABBOTT LAB ID SLOW-REACTING SUBSTANCES; AIRWAY SMOOTH-MUSCLE; MAST-CELLS; GUINEA-PIG; VASCULAR-PERMEABILITY; ALLERGEN CHALLENGE; LUNG-TISSUE; RELEASE; HISTAMINE; GENERATION AB Leukotrienes (LTs), in particular LTC4, LTD4, and LTE4, have been shown to be capable of participating in the induction of three related processes observed during the immediate reaction in bronchial asthma: edema formation, mucus secretion, and muscle contraction. Despite impressive evidence potentially implicating the LTs, the role of LTs in asthma is still unproved, and a positive answer to their critical actions in causing airflow obstruction will require studies with specific antagonists. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. NR 56 TC 48 Z9 48 U1 1 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD MAY PY 1991 VL 143 IS 5 SU S BP S96 EP S99 PG 4 WC Respiratory System SC Respiratory System GA FK899 UT WOS:A1991FK89900004 PM 2018251 ER PT J AU RAMPINO, NJ CHRAMBACH, A AF RAMPINO, NJ CHRAMBACH, A TI APPARATUS FOR GEL-ELECTROPHORESIS WITH CONTINUOUS MONITORING OF INDIVIDUAL DNA-MOLECULES BY VIDEO EPIFLUORESCENCE MICROSCOPY SO ANALYTICAL BIOCHEMISTRY LA English DT Article RP RAMPINO, NJ (reprint author), NICHHD,MACROMOLEC ANAL SECT,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 10 TC 8 Z9 8 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 MAY 1 PY 1991 VL 194 IS 2 BP 278 EP 283 DI 10.1016/0003-2697(91)90230-Q PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA FJ174 UT WOS:A1991FJ17400008 PM 1862931 ER PT J AU ZUCKERMAN, RL WHEELER, DM AF ZUCKERMAN, RL WHEELER, DM TI EFFECT OF HALOTHANE ON ARRHYTHMOGENIC RESPONSES INDUCED BY SYMPATHOMIMETIC AGENTS IN SINGLE-RAT HEART-CELLS SO ANESTHESIA AND ANALGESIA LA English DT Article DE ANESTHETICS, VOLATILE, HALOTHANE; HEART, ARRHYTHMIAS, HALOTHANE ID EPINEPHRINE-INDUCED ARRHYTHMIAS; GUINEA-PIG VENTRICLE; ACTION-POTENTIALS; CARDIAC MYOCYTES; PURKINJE-FIBERS; DEPRESSION; MECHANISM; DOGS; ISOFLURANE; THRESHOLD AB The combination of catecholamines and halothane has long been recognized as arrhythmogenic. The purpose of this study was to evaluate whether the mechanism of this interaction originates at the single cell level. The incidence of spontaneous contractile waves occurring between stimulated beats (interbeat waves), early aftercontractions, and late aftercontractions was measured in rat myocytes exposed to sympathomimetics with and without halothane. Each of these endpoints in single cells has the potential to produce arrhythmias in multicellular preparations. Interbeat waves and late aftercontractions were observed with isoproterenol (1 x 10(-7) M) and norepinephrine (1-3 x 10(-7) M). The incidence of these phenomena was significantly reduced in the presence of 0.30 mM halothane. Early aftercontractions occurred in the presence of isoproterenol (1 x 10(-7) M), norepinephrine (1-3 x 10(-7) M), and phenylephrine (5-10 x 10(-6) M). There was a statistically significant decrease in the incidence of early aftercontractions in the presence of 0.30 mM halothane. These results indicate that the mechanism behind the clinically observed increased arrhythmogenicity of catecholamines with halothane does not arise at the level of single ventricular cells because halothane inhibited sympathomimetic-induced arrhythmogenic activity in this model. The probable mechanisms rather include altered impulse propagation, which might lead to phenomena such as reentry. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. FU NIGMS NIH HHS [R29GM39568] NR 29 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 1991 VL 72 IS 5 BP 596 EP 603 PG 8 WC Anesthesiology SC Anesthesiology GA FH753 UT WOS:A1991FH75300005 PM 2018215 ER PT J AU STROBER, W SNELLER, MC AF STROBER, W SNELLER, MC TI IGA DEFICIENCY SO ANNALS OF ALLERGY LA English DT Review ID CIRCULATING IMMUNE-COMPLEXES; IMMUNOGLOBULIN-A DEFICIENCY; ANTI-IGA; SUBCLASS DEFICIENCY; BLOOD-DONORS; PEDIATRIC-PATIENTS; EPILEPTIC PATIENTS; GAMMA-GLOBULIN; HLA ANTIGENS; ANTIBODIES RP STROBER, W (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892, USA. NR 107 TC 53 Z9 54 U1 0 U2 2 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 0003-4738 J9 ANN ALLERGY JI Ann. Allergy PD MAY PY 1991 VL 66 IS 5 BP 363 EP 375 PG 13 WC Allergy SC Allergy GA FM355 UT WOS:A1991FM35500003 PM 2035899 ER PT J AU HARRIS, JO FRANK, JA PATRONAS, N MCFARLIN, DE MCFARLAND, HF AF HARRIS, JO FRANK, JA PATRONAS, N MCFARLIN, DE MCFARLAND, HF TI SERIAL GADOLINIUM-ENHANCED MAGNETIC-RESONANCE-IMAGING SCANS IN PATIENTS WITH EARLY, RELAPSING-REMITTING MULTIPLE-SCLEROSIS - IMPLICATIONS FOR CLINICAL-TRIALS AND NATURAL-HISTORY SO ANNALS OF NEUROLOGY LA English DT Article ID TOMOGRAPHY; MRI AB Six patients with early, mild, relapsing-remitting multiple sclerosis were studied with monthly gadolinium-enhanced magnetic resonance imaging scans for 8 to 11 months. Numerous enhancing lesions were observed irrespective of clinical activity. Four of the 6 patients had one or more enhancing lesions present on each examination. The other 2 patients had enhancing lesions noted in 7 and 9 of 11 months. In contrast, only two clinical exacerbations were observed during the study period. Neither the exacerbations nor other changes in symptoms or signs correlated with occurrence of the enhancing lesions. Enhancement generally persisted for less than 1 month. The opening of the blood-brain barrier as reflected by gadolinium enhancement on magnetic resonance imaging may represent ongoing disease activity in patients with mild, relapsing-remitting multiple sclerosis who are clinically stable. The frequency of these lesions appears to be sufficient to use as an outcome measure in clinical trials testing clinical efficacy in patients with early, relapsing-remitting multiple sclerosis. C1 NIH,NEUROIMMUNOL BRANCH,BLDG 10,ROOM 5B16,BETHESDA,MD 20892. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT INTERNAL MED,WASHINGTON,DC 20007. NR 16 TC 243 Z9 244 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1991 VL 29 IS 5 BP 548 EP 555 DI 10.1002/ana.410290515 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA FK274 UT WOS:A1991FK27400014 PM 1859184 ER PT J AU DUELAND, AN DEVLIN, M MARTIN, JR MAHALINGAM, R COHRS, R MANZ, H TROMBLEY, I GILDEN, D AF DUELAND, AN DEVLIN, M MARTIN, JR MAHALINGAM, R COHRS, R MANZ, H TROMBLEY, I GILDEN, D TI FATAL VARICELLA-ZOSTER VIRUS MENINGORADICULITIS WITHOUT SKIN INVOLVEMENT SO ANNALS OF NEUROLOGY LA English DT Note AB A 77-year-old man with T-cell lymphoma developed an acute fatal meningoradiculitis of cranial nerve roots and cauda equina, pathologically and virologically confirmed to be caused by varicella-zoster virus. This is the first report of fatal varicella-zoster virus-induced neurological disease in the absence of skin lesions. Varicella-zoster virus should be included in the differential diagnosis of acute radiculoneuropathy in the immuno-compromised patient, particularly because antiviral treatment for varicella-zoster virus exists. C1 UNIV COLORADO,SCH MED,DEPT MICROBIOL & IMMUNOL,DENVER,CO 80262. NIH,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20007. RP DUELAND, AN (reprint author), UNIV COLORADO,SCH MED,DEPT NEUROL,4200 E 9TH AVE,CAMPUS BOX B-182,DENVER,CO 80262, USA. FU NIA NIH HHS [AG-07347, AG-06127]; NINDS NIH HHS [NS-07321] NR 12 TC 53 Z9 53 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 MAY PY 1991 VL 29 IS 5 BP 569 EP 572 DI 10.1002/ana.410290520 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA FK274 UT WOS:A1991FK27400019 PM 1650163 ER PT J AU BURT, RK POIRIER, MC LINK, CJ BOHR, VA AF BURT, RK POIRIER, MC LINK, CJ BOHR, VA TI ANTINEOPLASTIC DRUG-RESISTANCE AND DNA-REPAIR SO ANNALS OF ONCOLOGY LA English DT Review ID HUMAN-TUMOR CELLS; NUCLEOTIDE EXCISION REPAIR; SISTER-CHROMATID EXCHANGE; INTERSTRAND CROSS-LINKING; RADIATION-DAMAGE REPAIR; HUMAN OVARIAN-CANCER; ESCHERICHIA-COLI; ALKYLATING-AGENTS; HUMAN-FIBROBLASTS; POLYMERASE-DELTA AB Important aspects of the DNA repair mechanisms in mammalian, and especially human, cells are reviewed. The DNA repair processes are essential in the maintenance of the integrity of the DNA and in the defense against cancer. It has recently been discovered that the DNA repair efficiency differs in different regions of the genome and that active genes are preferentially repaired. There is mounting evidence that DNA repair processes play a role in the development of drug resistance by tumor cells. We will discuss such data as well as further approaches to clarify the relationship between DNA repair and antineoplastic drug resistance. Specifically, there is an increasing need to investigate the intragenomic heterogeneity of DNA repair and correlate the repair efficiency in specific genes to aspects of drug resistance. We also discuss the therapeutic potential of inhibiting the DNA repair processes and thereby possibly overcoming drug resistance. C1 NCI,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C25,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NR 143 TC 18 Z9 18 U1 0 U2 2 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 MAY PY 1991 VL 2 IS 5 BP 325 EP 334 PG 10 WC Oncology SC Oncology GA FU423 UT WOS:A1991FU42300003 PM 1954176 ER PT J AU BROWN, PS PARENTEAU, GL HOLLAND, FW CLARK, RE AF BROWN, PS PARENTEAU, GL HOLLAND, FW CLARK, RE TI PRETREATMENT WITH NICARDIPINE PRESERVES VENTRICULAR-FUNCTION AFTER HYPOTHERMIC ISCHEMIC ARREST SO ANNALS OF THORACIC SURGERY LA English DT Article ID DILTIAZEM CARDIOPLEGIA; CALCIUM; PROTECTION; NIFEDIPINE; TISSUE; HEART AB Calcium antagonists have a protective effect on postischemic myocardial function when included in normothermic cardioplegia solutions. This effect varies with the calcium antagonist, but is generally lost under hypothermic conditions. The hypothesis tested was that a calcium antagonist would increase postischemic myocardial performance if given before the onset of hypothermic arrest. Isolated working rat hearts were used with an oxygenated modified Krebs-Henseleit buffer solution as a perfusion media. Rats were pretreated with 1 of 9 doses of a nicardipine solution (0 to 100-mu-g/kg, intraperitoneally) 20 minutes before excision of the heart. Nicardipine is a light-stable, water-soluble calcium antagonist with minimal myocardial depressant effects. The hearts were arrested for 25 minutes at 37-degrees-C or 93 minutes at 24-degrees-C with 20 mL of cardioplegia solution containing 0.05 mmol/L CaCl2. Postischemic performance and adenosine triphosphate content were used as determinants of efficacy. Eighty-three percent of 101 treated hearts recovered in contrast to a mortality of 50% in the 24 nontreated hearts. Pretreatment with 25-mu-g/kg significantly increased (p < 0.05) the percent recovery (compared with the nontreated group) of the following variables of cardiac function: systolic pressure, 74% to 96% (37-degrees-C), 76% to 90% (24-degrees-C); cardiac output, 61% to 90% (37-degrees-C), 62% to 84% (24-degrees-C); stroke work, 49% to 95% (37-degrees-C) 50% to 92% (24-degrees-C); and adenosine triphosphate, 76% to 87% (37-degrees-C), 58% to 68% (24-degrees-C). Progressive increases in postischemic function at 37-degrees and 24-degrees-C were seen as the dose of nicardipine was increased from 0 to 25-mu-g/kg and decreased function was seen with a pretreatment dose greater than 25-mu-g/kg of nicardipine. Pretreatment with nicardipine significantly improved postischemic myocardial performance under hypothermic conditions and should be administered or at least not discontinued before cardiac operations. C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. NR 24 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 1991 VL 51 IS 5 BP 739 EP 746 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA FK133 UT WOS:A1991FK13300008 PM 2025076 ER PT J AU REX, JH HANSON, LH AMANTEA, MA STEVENS, DA BENNETT, JE AF REX, JH HANSON, LH AMANTEA, MA STEVENS, DA BENNETT, JE TI STANDARDIZATION OF A FLUCONAZOLE BIOASSAY AND CORRELATION OF RESULTS WITH THOSE OBTAINED BY HIGH-PRESSURE LIQUID-CHROMATOGRAPHY SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COCCIDIOIDAL MENINGITIS; CEREBROSPINAL-FLUID AB An improved bioassay for fluconazole was developed. This assay is sensitive in the clinically relevant range (2 to 40-mu-g/ml) and analyzes plasma, serum, and cerebrospinal fluid specimens; bioassay results correlate with results obtained by high-pressure liquid chromatography (HPLC). Bioassay and HPLC analyses of spiked plasma, serum, and cerebrospinal fluid samples (run as unknowns) gave good agreement with expected values. Analysis of specimens from patients gave equivalent results by both HPLC and bioassay. HPLC had a lower within-run coefficient of variation (< 2.5% for HPLC versus < 11% for bioassay) and a lower between-run coefficient of variation (< 5% versus < 12% for bioassay) and was more sensitive (lower limit of detection, 0.1-mu-g/ml [versus 2-mu-g/ml for bioassay]). The bioassay is, however, sufficiently accurate and sensitive for clinical specimens, and its relative simplicity, low sample volume requirement, and low equipment cost should make it the technique of choice for analysis of routine clinical specimens. C1 NCI,CTR CLIN,DEPT PHARM,CLIN PHARMACOKINET LAB,BETHESDA,MD 20892. CALIF INST MED RES,SAN JOSE,CA 95128. SANTA CLARA VALLEY MED CTR,DEPT MED,DIV INFECT DIS,SAN JOSE,CA 95128. STANFORD UNIV,MED CTR,SCH MED,DEPT MED,DIV INFECT DIS,STANFORD,CA 94305. RP REX, JH (reprint author), NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BLDG 10,ROOM 11N107,BETHESDA,MD 20892, USA. NR 15 TC 50 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1991 VL 35 IS 5 BP 846 EP 850 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA FK462 UT WOS:A1991FK46200011 PM 1854166 ER PT J AU BERNSTEIN, EF GLASS, JM DEGRAFF, WG SCHLEGEL, R BLACK, C FISHER, JM COOK, SN GLATSTEIN, E RUSSO, A MITCHELL, JB AF BERNSTEIN, EF GLASS, JM DEGRAFF, WG SCHLEGEL, R BLACK, C FISHER, JM COOK, SN GLATSTEIN, E RUSSO, A MITCHELL, JB TI INVITRO PHOTODYNAMIC TREATMENT OF NORMAL AND HUMAN PAPILLOMA-VIRUS TRANSFECTED KERATINOCYTES WITH PHOTOFRIN-II AND RED-LIGHT SO ARCHIVES OF DERMATOLOGY LA English DT Article ID OXYGEN DEPENDENCE; THERAPY; CELLS; CANCER; PHOTOINACTIVATION; INFECTION; TUMORS; ASSAY; DNA AB Photodynamic therapy involves the use of light of appropriate wavelength to excite a photosensitizer to result in tissue destruction. The photosensitizer dihematoporphyrin ether and red light were used to treat normal and human papilloma virus type 18-transfected keratinocytes in vitro. Although both cell lines were sensitive to treatment, normal keratinocytes retained more dihematoporphyrin ether and were more sensitive to photodynamic therapy than were transfected cells. In vitro data fail to show the selective retention of dihematoporphyrin ether reported elsewhere in the literature in papillomas and tumors. We did not find selective uptake or retention of dihematoporphyrin ether by human papilloma virus-transfected cells, despite previously published in vivo data to the contrary. Dihematoporphyrin ether retention and thus selective photosensitivity of papillomas in vivo is not caused by individual cellular differences in the processing of dihematoporphyrin ether. In addition, because in vitro results may not parallel in vivo results, both in vivo and in vitro models must be investigated in the study of phototherapeutic agents. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20057. RP BERNSTEIN, EF (reprint author), HAHNEMANN UNIV,DIV DERMATOL,MAIL STOP 401,BROAD & VINE ST,PHILADELPHIA,PA 19102, USA. NR 30 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 1991 VL 127 IS 5 BP 683 EP 687 PG 5 WC Dermatology SC Dermatology GA FL673 UT WOS:A1991FL67300009 PM 1850973 ER PT J AU ROY, A DEJONG, J LAMPARSKI, D ADINOFF, B GEORGE, T MOORE, V GARNETT, D KERICH, M LINNOILA, M AF ROY, A DEJONG, J LAMPARSKI, D ADINOFF, B GEORGE, T MOORE, V GARNETT, D KERICH, M LINNOILA, M TI MENTAL-DISORDERS AMONG ALCOHOLICS - RELATIONSHIP TO AGE OF ONSET AND CEREBROSPINAL-FLUID NEUROPEPTIDES SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAZEPAM-BINDING INHIBITOR; ANTISOCIAL PERSONALITY; DEPRESSED-PATIENTS; FAMILY HISTORY; CSF; PREVALENCE; DEPENDENCE; PSYCHOPATHOLOGY; VALIDITY; STATES AB Eighty-one percent of 339 alcoholics participating in a research program were found to have associated mental disorders. Alcoholics with onset of heavy drinking before 20 years of age had significantly more antisocial personality traits, drug abuse, bipolar disorder, panic disorder, suicide attempts, and paternal alcoholism than alcoholics with onset after age 20 years. Alcoholics with onset before and after 20 years of age also differed significantly from each other for cerebrospinal fluid concentrations of diazepam-binding inhibitor and somatostatin. These results support the notion that age of onset may delineate subgroups of alcoholics with significant clinical and neurochemical differences. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,ROOM 3B19,BLDG 10,BETHESDA,MD 20892. NR 46 TC 52 Z9 53 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 MAY PY 1991 VL 48 IS 5 BP 423 EP 427 PG 5 WC Psychiatry SC Psychiatry GA FK913 UT WOS:A1991FK91300005 PM 1673594 ER PT J AU ROY, A DEJONG, J LAMPARSKI, D GEORGE, T LINNOILA, M AF ROY, A DEJONG, J LAMPARSKI, D GEORGE, T LINNOILA, M TI DEPRESSION AMONG ALCOHOLICS - RELATIONSHIP TO CLINICAL AND CEREBROSPINAL-FLUID VARIABLES SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAZEPAM-BINDING INHIBITOR; ELECTROCHEMICAL DETECTION; ACID; TRANSMISSION; SUICIDE; ETHANOL; MEN AB Although depression is common among alcoholics, its determinants are poorly understood. Among 339 alcoholics, 111 (33%) had a history of major depression. Depressed, compared with never-depressed alcoholics, had a higher daily alcohol intake, more lifetime diagnoses of other anxiety and affective disorders and drug abuse, more had attempted suicide, and more reported alcoholism in both parents. Depressed alcoholics also had significantly lower cerebrospinal fluid levels of the dopamine metabolite homovanillic acid and of gamma-aminobutyric acid. Among subgroups of depressed alcoholics, secondary compared with primary depressives were more often divorced, of lower social status, with an earlier onset of alcoholism, and higher Michigan Alcohol Screening Test scores. Secondary depressives also had significantly lower cerebrospinal fluid concentrations of homovanillic acid than never depressed alcoholics. These results suggest that certain psychosocial variables, alcohol consumption, and neurochemical variables may be specifically associated with depression in alcoholics. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,ROOM 3B19,BLDG 10,BETHESDA,MD 20892. NR 35 TC 116 Z9 117 U1 1 U2 1 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 MAY PY 1991 VL 48 IS 5 BP 428 EP 432 PG 5 WC Psychiatry SC Psychiatry GA FK913 UT WOS:A1991FK91300006 PM 2021295 ER PT J AU LIMSON, R GOLDMAN, D ROY, A LAMPARSKI, D RAVITZ, B ADINOFF, B LINNOILA, M AF LIMSON, R GOLDMAN, D ROY, A LAMPARSKI, D RAVITZ, B ADINOFF, B LINNOILA, M TI PERSONALITY AND CEREBROSPINAL-FLUID MONOAMINE METABOLITES IN ALCOHOLICS AND CONTROLS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID 5-HYDROXYINDOLEACETIC ACID; ELECTROCHEMICAL DETECTION; GLUCOSE-METABOLISM; SUICIDAL-BEHAVIOR; AMINE METABOLITES; IMPULSIVENESS; AGGRESSION; SEROTONIN AB Alcoholics as a group have been consistently reported to show differences from controls on various personality inventories. Moreover, neurobiologic substrates have been postulated to underlie personality dimensions. Therefore, we compared alcoholics with controls on measures of personality and investigated relationships between measures of personality and cerebrospinal fluid monoamine metabolite concentrations. The alcoholics were significantly different from controls on many personality measurements. There were significant, negative correlations between interview-derived lifetime aggression scores and cerebrospinal fluid concentrations of both the serotonin metabolite 5-hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid. However, there were no significant correlations between any cerebrospinal fluid monoamine metabolite concentrations and scores on personality inventories. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,BLDG 10,ROOM 3B19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 32 TC 150 Z9 150 U1 1 U2 1 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 MAY PY 1991 VL 48 IS 5 BP 437 EP 441 PG 5 WC Psychiatry SC Psychiatry GA FK913 UT WOS:A1991FK91300007 PM 1708656 ER PT J AU OBARZANEK, E LESEM, MD GOLDSTEIN, DS JIMERSON, DC AF OBARZANEK, E LESEM, MD GOLDSTEIN, DS JIMERSON, DC TI REDUCED RESTING METABOLIC-RATE IN PATIENTS WITH BULIMIA-NERVOSA SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ENERGY-EXPENDITURE; THYROID-HORMONES; ANOREXIA-NERVOSA; CALORIC REQUIREMENTS; OVERWEIGHT WOMEN; HUMAN OBESITY; HUMAN-BEINGS; BODY-FAT; SEMISTARVATION; CARBOHYDRATE AB To determine whether there was a metabolic basis for recent reports that bulimic patients had low energy requirements for weight maintenance, energy expenditure measurements were made in 15 women with bulimia nervosa during abstinence from bingeing and vomiting. Resting metabolic rate, adjusted for differences in lean body mass, was significantly lower in bulimics (mean +/- SE, 4201 +/- 126 kJ/d) than healthy volunteers (4694 +/- 172 kJ/d). Bulimic patients had a blunted increase in oxygen consumption in response to low and moderate levels of exercise (421 +/- 16 and 689 +/- 17 mL/min) compared with values for healthy volunteers (491 +/- 28 and 795 +/- 26 mL/min). Plasma triiodothyronine (1.1 +/- 0.07 vs 1.4 +/- 0.08 nmol/L) levels, plasma norepinephrine levels in supine (0.58 +/- 0.04 vs 1.06 +/- 0.17 nmol/L) and standing (1.34 +/- 0.15 vs 2.46 +/- 0.30 nmol/L) subjects, and the increase in norepinephrine levels during orthostatic challenge (0.76 +/- 0.15 vs 1.40 +/- 0.25 nmol/L) all were significantly less in bulimics than volunteers. These results are consistent with previous reports of decreased energy requirements for weight maintenance and decreased plasma levels of metabolism-related hormones in patients with bulimia. However, the effects of reduced energy intake in metabolic studies of patients with bulimia need to be further investigated. C1 NIMH,CLIN SCI LAB,BIOMED PSYCHIAT SECT,BETHESDA,MD 20892. NR 54 TC 21 Z9 21 U1 9 U2 11 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 MAY PY 1991 VL 48 IS 5 BP 456 EP 462 PG 7 WC Psychiatry SC Psychiatry GA FK913 UT WOS:A1991FK91300010 PM 2021298 ER PT J AU NORQUIST, G WELLS, K AF NORQUIST, G WELLS, K TI MENTAL-HEALTH NEEDS OF THE UNINSURED SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; NON-HISPANIC WHITES; LOS-ANGELES; MEXICAN-AMERICANS; SERVICES; CARE; PREVALENCE; POOR AB As many as 37 million Americans have no medical insurance, but no data exist on the mental health needs of community samples of the uninsured. Using interview data from a household sample in Los Angeles, we found that the uninsured had a higher prevalence of serious psychiatric disorder (16%) than those with private health insurance (12%), but had a prevalence similar to those with Medicaid (18%). Access to mental health services among those with a psychiatric disorder was similar in the uninsured (14.5%) and those with private insurance (18%) but was less than those with Medicaid coverage (42%). These results indicate that the uninsured have a great potential need for mental health services and that access might be improved through insurance plans such as Medicaid. However, further study is needed to determine the adequacy and quality of services provided under Medicaid and whether such a plan would improve access for an uninsured population such as the one studied here. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. RP NORQUIST, G (reprint author), NIMH,DIV APPL & SERV RES,ROOM 18-C-26,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. FU NIMH NIH HHS [MH-38870, MH-33883, MH-34224] NR 26 TC 36 Z9 36 U1 0 U2 0 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 MAY PY 1991 VL 48 IS 5 BP 475 EP 478 PG 4 WC Psychiatry SC Psychiatry GA FK913 UT WOS:A1991FK91300013 PM 2021301 ER PT J AU BARTH, RJ DANFORTH, DN VENZON, DJ STRAUS, KL DANGELO, T MERINO, MJ GERBER, L AF BARTH, RJ DANFORTH, DN VENZON, DJ STRAUS, KL DANGELO, T MERINO, MJ GERBER, L TI LEVEL OF AXILLARY INVOLVEMENT BY LYMPH-NODE METASTASES FROM BREAST-CANCER IS NOT AN INDEPENDENT PREDICTOR OF SURVIVAL SO ARCHIVES OF SURGERY LA English DT Article ID CARCINOMA; MASTECTOMY; TRIAL; MANAGEMENT AB We examined the relationship of axillary level of lymph node metastases from clinical stage I and II breast cancer to overall survival and disease-free survival rates in 135 patients who underwent complete axillary lymph node dissection to determine if anatomic level of axillary involvement (I vs II vs III) is an independent prognostic factor. All patients underwent either modified radical mastectomy or lumpectomy with axillary dissection and whole breast radiotherapy for breast cancer. Median follow-up was 6.9 years. We found no difference in overall survival or disease-free survival between patients whose highest or only level of axillary involvement was level I compared with patients whose highest or only level was II. Although patients whose highest level of nodal involvement was III had significantly worse overall survival and disease-free survival rates than patients whose highest nodal involvement was I or II, when patients were stratified by the total number of positive nodes (one to three vs four or more), there was no difference in overall survival or disease-free survival rates between levels, I, II, and III. These findings indicate that the level of axillary involvement for stage II breast cancer is not of independent prognostic significance. C1 NCI,SURG BRANCH,BLDG 10,ROOM 2B38,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT REHABIL MED,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 18 TC 21 Z9 22 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 MAY PY 1991 VL 126 IS 5 BP 574 EP 577 PG 4 WC Surgery SC Surgery GA FK713 UT WOS:A1991FK71300010 PM 2021339 ER PT J AU JAMES, RW HOCHSTRASSER, AC BORGHINI, I MARTIN, B POMETTA, D HOCHSTRASSER, D AF JAMES, RW HOCHSTRASSER, AC BORGHINI, I MARTIN, B POMETTA, D HOCHSTRASSER, D TI CHARACTERIZATION OF A HUMAN HIGH-DENSITY LIPOPROTEIN-ASSOCIATED PROTEIN, NA1/NA2 - IDENTITY WITH SP-40,40, AN INHIBITOR OF COMPLEMENT-MEDIATED CYTOLYSIS SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE LIPOPROTEINS; HIGH DENSITY LIPOPROTEINS; ATHEROSCLEROSIS; COMPLEMENT; SP-40,40; APOLIPOPROTEIN-A-I ID DIMENSIONAL GEL-ELECTROPHORESIS; HUMAN ATHEROSCLEROTIC LESIONS; APOLIPOPROTEIN-A-II; NORMAL HUMAN-SERUM; HUMAN-PLASMA; S-PROTEIN; FLUID; STEP; IV AB Two peptides, NA1 and NA2, which we previously suggested to be associated with high density lipoproteins (HDLs), have been purified. Polyclonal antibodies against each peptide and a monoclonal antibody against NA2 have been used to further characterize them and their association with HDL. Immunoblotting studies revealed that the peptides form a complex of molecular mass of approximately 80 kd. Agarose gel filtration showed coelution of NA1/NA2 and apolipoprotein (apo) A-I, the structural protein of HDL. This was confirmed by fast protein liquid chromatography, which further indicated that up to 60% of NA1/NA2 was located within the lower density range of the HDL spectrum. Complementary studies with anti-apo A-I immunoaffinity columns provided evidence that at least 40% of NA1/NA2 was associated with HDL, an association easily disrupted by ultracentrifugal manipulation. Finally, partial amino acid sequences showed virtually complete homology with a recently identified protein, SP-40,40, or cytolysis inhibitor. The protein is suggested to have a powerful inhibitory effect on complement-mediated cell lysis. Our results could thus furnish an explanation for the previously observed modulating influence of HDL on complement activity. C1 UNIV GENEVA,HOP CANTONAL,UNITE IMAGERIE,CH-1211 GENEVA 4,SWITZERLAND. NIH,BETHESDA,MD 20892. RP JAMES, RW (reprint author), UNIV GENEVA,HOP CANTONAL,DEPT MED,DIV DIABETOL,LIPID LAB,24 RUE MICHELI CREST,CH-1211 GENEVA 4,SWITZERLAND. NR 39 TC 68 Z9 70 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD MAY-JUN PY 1991 VL 11 IS 3 BP 645 EP 652 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FM030 UT WOS:A1991FM03000024 PM 1903064 ER PT J AU KALLMAN, D SCOTT, WW HOCHBERG, MC WIGLEY, FM TOBIN, JD AF KALLMAN, D SCOTT, WW HOCHBERG, MC WIGLEY, FM TOBIN, JD TI COMMENT ON THE RADIOGRAPHIC GRADING SCALES FOR OSTEOARTHRITIS OF THE HAND - REPLY SO ARTHRITIS AND RHEUMATISM LA English DT Letter C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD. NIA,BALTIMORE,MD 21224. RP KALLMAN, D (reprint author), MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1991 VL 34 IS 5 BP 639 EP 639 PG 1 WC Rheumatology SC Rheumatology GA FL399 UT WOS:A1991FL39900019 ER PT J AU BIBEN, M SYMMES, D AF BIBEN, M SYMMES, D TI PLAYBACK STUDIES OF AFFILIATIVE VOCALIZING IN CAPTIVE SQUIRREL-MONKEYS - FAMILIARITY AS A CUE TO RESPONSE SO BEHAVIOUR LA English DT Article ID SAIMIRI-SCIUREUS; PARUS-MAJOR; ALARM CALLS; RECOGNITION; VOCALIZATIONS; EXCHANGES; DISTANCE; PRIMATE; SONG AB 1. A captive social group of squirrel monkeys in an outdoor habitat was presented with recorded chuck calls obtained from conspecific neighbors, neighbors of another Saimiri species, conspecific strangers, and members of the target group itself. 2. Responses to playback of chucks from their own group members were indistinguishable (in frequency, type, and latency) from those made to spontaneously emitted chucks. 3. The most familiar chucks (own group playbacks) received affiliative (chuck) responses as frequently as did spontaneously emitted chucks. Chuck playbacks from neighbors (conspecific or not) and strangers got significantly fewer chuck responses. 4. Chuck playbacks from conspecific neighbors received responses indicating mild interest, those from neighbors of another species received agonistic vocal responses, and those from conspecific strangers received both mild interest and agonism. 5. Own group chucks with multiple repeating elements elicited a higher response rate than single element chucks. This effect did not obtain for playbacks from animals outside the target group. 6. Results suggest that playback techniques can be successful with close range affiliative vocalizations like the chuck and that familiarity, species identity, and acoustic structure are all important variables. RP BIBEN, M (reprint author), NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892, USA. NR 25 TC 23 Z9 23 U1 0 U2 4 PU E J BRILL PI LEIDEN PA PO BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 J9 BEHAVIOUR JI Behaviour PD MAY PY 1991 VL 117 BP 1 EP 19 DI 10.1163/156853991X00094 PN 1-2 PG 19 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA FM620 UT WOS:A1991FM62000001 ER PT J AU REGAZZI, R ULLRICH, S KAHN, RA WOLLHEIM, CB AF REGAZZI, R ULLRICH, S KAHN, RA WOLLHEIM, CB TI REDISTRIBUTION OF ADP-RIBOSYLATION FACTOR DURING STIMULATION OF PERMEABILIZED CELLS WITH GTP ANALOGS SO BIOCHEMICAL JOURNAL LA English DT Article ID CA-2+-INDEPENDENT INSULIN-SECRETION; BINDING-PROTEIN; PLASMA-MEMBRANE; GUANINE-NUCLEOTIDES; ADENYLATE-CYCLASE; BOVINE BRAIN; VESICLES; PURIFICATION; TRANSPORT; PLATELETS AB Low-molecular-mass GTP-binding proteins of the ras family were analysed by [P-32]GTP binding after PAGE and transfer to nitrocellulose membranes. By this technique, several GTP-binding proteins in the 20-30 kDa range were detected in both cytosolic and microsomal fractions of RINm5F cells. One of these, displaying an apparent molecular mass of about 20 kDa and a pI of 6.7, was mainly cytosolic and was shown to be the ADP-ribosylation factor (ARF) by using specific antibodies. When permeabilized RINm5F cells were incubated with the stable GTP analogues guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and guanosine 5'-[beta-gamma-imido]triphosphate (p[NH]ppG) the amount of ARF increased in a fraction containing both Golgi and plasma-membrane markers, but not in the fraction containing secretory granules, mitochondria and lysosomes. GTP, GDP and its beta-thio analogue did not enhance ARF binding to membranes. smg25/rab3 and rho, as well as all the other small GTP-binding proteins detected by the [P-32]GTP binding, did not redistribute under these conditions. As GTP[S] stimulates insulin secretion in these cells, we also examined the relationship between ARF translocation and insulin secretion. Both phenomena were elicited by GTP[S] with an EC50 (median effective concentration) of about 10-mu-M. p[NH]ppG was equipotent with GTP[S] in inducing insulin secretion (EC50 about 10-mu-M), but higher concentrations (about 500-mu-M) were required to achieve the same maximal ARF redistribution. These results suggest that: (1) ARF is subject to cycling between a membrane-associated and a free/loosely attached form, determined by the species of bound guanine nucleotide; (2) ARF alone does not seem to regulate exocytosis in insulin-secreting cells. C1 NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BETHESDA,MD 20892. RP REGAZZI, R (reprint author), UNIV GENEVA,DEPT MED,DIV BIOCHIM CLIN,9 AVE CHAMPEL,CH-1211 GENEVA 4,SWITZERLAND. NR 27 TC 48 Z9 48 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 MAY 1 PY 1991 VL 275 BP 639 EP 644 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FL173 UT WOS:A1991FL17300016 PM 1903923 ER PT J AU BONVINI, E DEBELL, KE TAPLITS, MS BRANDO, C LAURENZA, A SEAMON, K HOFFMAN, T AF BONVINI, E DEBELL, KE TAPLITS, MS BRANDO, C LAURENZA, A SEAMON, K HOFFMAN, T TI A ROLE FOR GUANINE-NUCLEOTIDE-BINDING PROTEINS IN MEDIATING T-CELL-RECEPTOR COUPLING TO INOSITOL PHOSPHOLIPID HYDROLYSIS IN A MURINE T-HELPER (TYPE-II) LYMPHOCYTE CLONE SO BIOCHEMICAL JOURNAL LA English DT Article ID CYTOPLASMIC FREE CALCIUM; ANTIGEN RECEPTOR; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; REGULATORY PROTEIN; CHOLERA-TOXIN; POLYPHOSPHOINOSITIDE PHOSPHODIESTERASE; SURFACE MOLECULES; PERTUSSIS TOXIN; B-CELLS AB Perturbation of the T-cell receptor (TCR) complex is followed by the rapid hydrolysis of inositol phospholipids (InsPL) by phospholipase C (PLC), producing diacylglycerol and inositol phosphates, which act as second messengers in signal transduction. The mechanism coupling the TCR to InsPL hydrolysis is not clearly defined, and no information is available on this mechanism in the CD4+ helper subset of T-lymphocytes (Th). We have tested the hypothesis that guanine-nucleotide-binding proteins (G-proteins) may couple the TCR to PLC in a murine Th type II (Th2) cell clone. Cell permeabilization with streptolysin O (SLO) or tetanolysin (TL) was used to allow membrane-impermeable nucleotides access to intracellular sites of action. Exposure of permeabilized Th2 cells to guanosine 5"-[gamma-thio]triphosphate (GTP-gamma-S), a non-hydrolysable GTP analogue, resulted in a 2.1-2.5-fold increase in inositol phosphate generation. Similarly, perturbation of the TCR with the monoclonal antibody 145.2C11 (directed against the epsilon-chain of the CD3 component of the TCR) resulted in a 3.1-4.2-fold increase in InsPL hydrolysis by permeabilized cells. Both lysins were similarly effective in allowing GTP-gamma-S induction of InsPL hydrolysis, but TL-permeabilized cells responded better to TCR perturbation than SLO-treated cells. A role for G-proteins in TCR coupling to PLC was further supported by the inhibition of TCR-induced InsPL hydrolysis by guanosine 5'-[beta-thio]diphosphate (GDP-beta-S), a guanine nucleotide analogue that inhibits G-protein function. ATP was required for TCR-mediated InsPL hydrolysis, and potentiated GTP-gamma-S-induced hydrolysis. Other nucleotides (i.e. CTP, GDP, ITP) did not affect the response. These data indicate that G-proteins may contribute to the regulation of PLC activation in Th2 cells, coupling it to the TCR. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP BONVINI, E (reprint author), US FDA,DIV HEMATOL,CELL BIOL LAB,NIH CAMPUS,BLDG 29,ROOM 231,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 50 TC 17 Z9 17 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 MAY 1 PY 1991 VL 275 BP 689 EP 696 PN 3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FL173 UT WOS:A1991FL17300024 PM 1645519 ER PT J AU RAVINDRANATH, V BOYD, MR AF RAVINDRANATH, V BOYD, MR TI EFFECT OF MODULATORS OF GLUTATHIONE SYNTHESIS ON THE HEPATOTOXICITY OF 2-METHYLFURAN SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID PULMONARY GLUTATHIONE; METABOLIC-ACTIVATION; PROTECTIVE ROLE; CYSTEINE; TOXICITY; CELLS; L-2-OXOTHIAZOLIDINE-4-CARBOXYLATE; SENSITIVITY; DEPLETION; TURNOVER AB Treatment of male Sprague-Dawley rats with buthionine sulfoximine (BSO), prior to administration of carbon-14(C-14)-labelled 2-methylfuran (2MF) caused a marked decrease in the covalent binding of C-14-labelled 2MF metabolites to both DNA and protein, although there was no apparent change in the distribution of the labelled parent 2MF. BSO pretreatment also protected against hepatotoxicity of 2MF, as indicated by lower serum glutamic pyruvic transaminase (GPT) levels. Pretreatment with BSO offered protection only if administered 1.5 hr before 2MF dosage. Administration of 2MF, 4 and 6 hr after BSO resulted in manifestation of the hepatotoxicity of 2MF. Prior treatment with diethylmaleate (DEM), increased covalent binding of [C-14]2MF to liver proteins and also elevated serum GPT levels. Thus, depletion of tissue glutathione (GSH) by two different chemicals acting by different mechanisms produced opposite effects on the covalent binding and toxicity of 2MF. Pretreatment with L-2-oxothiazolidine-4-carboxylate (OTZ), a promoter of GSH biosynthesis, increased the hepatic covalent binding of [C-14]2MF and potentiated hepatotoxicity. However, administration of OTZ and BSO prior to an i.p. dose of 100 mg/kg of 2MF, decreased the hepatic covalent binding of [C-14]2MF and decreased the hepatotoxicity. The marked instability of the GSH conjugate of the reactive metabolite of 2MF may account for the potentiation of hepatotoxicity of 2MF by OTZ. A single s.c. dose of BSO, caused a transient increase in plasma cystine levels concurrent with the depletion of liver GSH. Administration of 2MF, 1.5 hr after BSO, significantly decreased plasma cystine levels as compared to control animals that received vehicle alone. Pretreatment with BSO also resulted in increased excretion of urinary metabolites in 2MF treated animals as compared to animals receiving 2MF alone. Thus, BSO probably protects against hepatoxicity of 2MF by indirectly causing more detoxification of the reactive metabolite of 2MF, as it does not alter the distribution of unmetabolized 2MF and does not have any apparent effect on the microsomal mixed-function oxidase which mediates the activation of 2MF. The enhanced detoxification of 2MF in BSO treated animals appears independent of the depleted GSH levels; it may result from increased availability of a better alternative nucleophile (i.e. cysteine), capable of conjugating with acetyl acrolein. Acetyl acrolein (AA) appears to be the principal reactive metabolite of 2MF which binds covalently to tissues. Previous in vitro studies have shown that cysteine is a better trapping agent of AA than GSH or N-acetyl cysteine. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,PROGRAM DEV RES GRP,FREDERICK,MD 21702. NR 25 TC 13 Z9 13 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 1 PY 1991 VL 41 IS 9 BP 1311 EP 1318 DI 10.1016/0006-2952(91)90102-B PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FF426 UT WOS:A1991FF42600007 PM 2018563 ER PT J AU CARUBELLI, R GRAHAM, SA MCCAY, PB FRIEDMAN, FK AF CARUBELLI, R GRAHAM, SA MCCAY, PB FRIEDMAN, FK TI PREVENTION OF 2-ACETYLAMINOFLUORENE-INDUCED LOSS OF NUCLEAR-ENVELOPE CYTOCHROME-P450 BY THE SIMULTANEOUS ADMINISTRATION OF 3-METHYLCHOLANTHRENE SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID RATS FED 2-ACETYLAMINOFLUORENE; HYPERPLASTIC NODULES; BUTYLATED HYDROXYTOLUENE; DIETARY FATS; LIVER; INDUCTION; HYDROXYLASE; MEMBRANES AB Rats fed a basal diet containing 0.05% (w/w) 2-acetylaminofluorene (AAF) for 3 weeks showed a 50% loss of hepatic nuclear envelope cytochrome P450, whereas microsomal P450 remained at control levels. A similar dietary treatment with 0.004%(w/w) 3-methylcholanthrene (MC) caused moderate losses (20-25%) of cytochrome P450 in both nuclear envelopes and microsomes. Administration of the basal diet supplemented with a mixture of AAF (0.05%) plus MC (0.004%) resulted in a preservation of control levels of nuclear envelope cytochrome P450 and a 30% elevation of microsomal P450. Immunoblot analysis revealed that AAF alone, or in concert with MC, induced comparable levels of the P450d form. Induction of cytochrome P450c by dietary MC was detected only when MC was fed together with AAF. As previously found for butylated hydroxytoluene (BHT), the protective effect of dietary MC against hepatocarcinogenesis in AAF-fed rats correlate with a preservation of nuclear envelope cytochrome P450 content and with the induction of cytochrome P450c. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP CARUBELLI, R (reprint author), OKLAHOMA MED RES FDN,MOLEC TOXICOL RES GRP,825 NE 13TH ST,OKLAHOMA CITY,OK 73104, USA. RI Friedman, Fred/D-4208-2016 NR 23 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 1 PY 1991 VL 41 IS 9 BP 1331 EP 1334 DI 10.1016/0006-2952(91)90105-E PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FF426 UT WOS:A1991FF42600010 PM 2018565 ER PT J AU BRECHBIEL, MW GANSOW, OA AF BRECHBIEL, MW GANSOW, OA TI BACKBONE-SUBSTITUTED DTPA LIGANDS FOR Y-90 RADIOIMMUNOTHERAPY SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; THERAPY AB Four new bifunctional diethylenetriaminepentaacetic acid (DTPA) ligands were synthesized to provide an improved chelating agent for radioimmunotherapy with Y-90. The new DTPA ligands contained a 4-isothiocyanatobenzyl group (pSCNBz) substituted onto the carbon backbone of DTPA for use in linkage to immunoprotein. Methyl groups were strategically incorporated onto the backbone of the ligands via a peptide route to provide 2-pSCNBz-5-Me-DTPA (2) and 3-Me-6-pSCNBz-DTPA (3). Addition of these functionalities was expected to sterically hinder the release of radiometal from the chelate. A new monosubstituted ligand, 3-pSCNBz-DTPA (4), was also prepared in order to determine whether a shift in position of the linking group had an effect on the in vivo stability of the yttrium complex. Additionally, by modification of known methods, a disubstituted DTPA ligand, 2-pSCNBz-6-Me-DTPA (1), was prepared. RP BRECHBIEL, MW (reprint author), NCI,RADIAT ONCOL BRANCH,CHEM SECT,BLDG 10,RM B3B69,BETHESDA,MD 20892, USA. NR 35 TC 131 Z9 132 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 1991 VL 2 IS 3 BP 187 EP 194 DI 10.1021/bc00009a008 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA GB085 UT WOS:A1991GB08500008 PM 1932218 ER PT J AU GUTIERREZCORREA, J HOD, M PASSONEAU, JV FREINKEL, N AF GUTIERREZCORREA, J HOD, M PASSONEAU, JV FREINKEL, N TI GLYCOGEN AND ENZYMES OF GLYCOGEN-METABOLISM IN RAT EMBRYOS AND FETAL ORGANS SO BIOLOGY OF THE NEONATE LA English DT Article DE GLYCOGEN; RAT EMBRYO; RAT FETUS ID LIVER; PHOSPHORYLASE; SYNTHASE; GLUCOSE; TISSUES AB Glycogen content and the enzymes of glycogen metabolism have been measured in the postimplantation rat embryo over a period ranging from 9.5 to 18.5 days of gestation. The earliest periods studied were at days 9.5 and 10.5 of gestation, when the yolk sac becomes vascularized and heart beat is first established. The next intervals were at days 10.5-11.5 when vascular connections via the allantoic placenta are formed. At 14.5 and 18.5 days of development, 4 entire organs were analyzed; heart, liver, kidney and brain. The metabolic apparatus of glycogen metabolism was concentrated in the embryo at 10.5 days, then the heart region, and in the heart itself at later stages. C1 NIAAA,METAB & MOLEC BIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852. TEL AVIV UNIV,SACKLER SCH MED,BEILINSON MED CTR,PETAH TIQWA,ISRAEL. UNIV NACL MAYOR SAN MARCOS,CTR INVEST BIOQUIM & NUTR,LIMA,PERU. FU NIDDK NIH HHS [DK07169, DK10699] NR 23 TC 12 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0006-3126 J9 BIOL NEONATE JI Biol. Neonate PD MAY PY 1991 VL 59 IS 5 BP 294 EP 302 PG 9 WC Pediatrics SC Pediatrics GA FP034 UT WOS:A1991FP03400005 PM 1908323 ER PT J AU VINCENT, JS LEVIN, IW AF VINCENT, JS LEVIN, IW TI RAMAN-SPECTROSCOPIC STUDIES OF DIMYRISTOYLPHOSPHATIDIC ACID AND ITS INTERACTIONS WITH FERRICYTOCHROME-C IN CATIONIC BINARY AND TERNARY LIPID-PROTEIN COMPLEXES SO BIOPHYSICAL JOURNAL LA English DT Article ID CYTOCHROME-C; MEMBRANE-STRUCTURE; PHOSPHATIDIC-ACID; DEUTERATED PHOSPHOLIPIDS; SPECTRAL PARAMETERS; PACKING PROPERTIES; BILAYER MEMBRANES; PHOSPHATIDYLCHOLINE; MULTILAYERS; CALCIUM AB The vibrational Raman spectra of both pure 1-alpha-dimyristoylphosphatidic acid (DMPA) liposomes and DMPA multilayers reconstituted with ferricytochrome c at pH 7 and pH 4, with either sodium or calcium as the cation, are reported as a function of temperature. Multilayers composed of a 1:1 mol ratio DMPA and dimyristoylphosphatidylcholine with perdeuterated acyl chains (DMPC-d54) have also been reconstituted with approximately 10(-4) M ferricytochrome c for Raman spectroscopic observation. Total integrated band intensities and relative peak height intensity ratios, two spectral Raman scattering parameters used to characterize bilayer properties, are sensitive to the presence of both ferricytochrome c and the cation in the reconstituted liposomes. Temperature profiles, derived from the various Raman intensity parameters for the 3,100-2,800 cm-1 lipid acyl chain C-H stretching mode region specifically reflect bilayer perturbations due to the interactions of ferricytochrome c. At pH 4 the calcium DMPA multilamellar gel to liquid crystalline phase transition temperatures T(m), defined by either the C-H stretching mode I2850/I2880 and I2935/I2880 peak height intensity ratios, are 58.5 +/- 0.5-degrees-C and 60.0 +/- 0.3-degrees-C, respectively. This difference in T(m)'s resolves the phase transition process into first an expansion of the lipid lattice and then a melting of the lipid acyl chains. At pH 7 the calcium DMPA liposomes show no distinct phase transition characteristics below 75-degrees-C. For sodium DMPA liposomes reconstituted with ferricytochrome c at either pH 4.0 or pH 7.0, spontaneous Raman spectra show altered lipid structures at temperatures above 40-degrees-C. Resonance Raman spectra indicate that ferricytochrome c reconstituted in either calcium or sodium DMPA liposomes changes irreversibly above T(m). For either the binary lipid or ternary lipid-protein systems reconstituted with DMPC-d54, linewidth parameters of the DMPC-d54 acyl chain CD2 symmetric stretching modes at 2,103 cm-1 provide a sensitive measure of the conformational and dynamic properties of the perdeuterated lipid component, while the 3,000 cm-1 C-H spectral region reflects the bilayer characteristics of the DMPA species in the complex. Although calcium clearly induces a lateral phase separation in the DMPA/DMPC-d54 system at pH 7.5 (Kouaouci, R., J. R. Silvius, I. Graham, and M. Pezolet. 1985. Biochemistry. 24:7132-7140), no distinct lateral segregation of the lipid components is observed in the mixed DMPA/DMPC-d54 lipid system in the presence of either ferricytochrome c or the sodium and calcium cations at pH 4.0. However, domain formation, consisting of regions rich in DMPA and DMPC-d54, respectively, is suggested for the calcium binary lipid mixture at pH 4.0 by the different values for T(m) and DELTA-T characterizing the DMPA and DMPC-d54 species. Spectral evidence strongly suggests that ferricytochrome c also induces domain formation in the ternary lipid-protein mixtures at pH 7.0, but only for the sodium cation. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RP VINCENT, JS (reprint author), UNIV MARYLAND,DEPT CHEM,CATONSVILLE,MD 21228, USA. NR 37 TC 14 Z9 14 U1 0 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 1991 VL 59 IS 5 BP 1007 EP 1021 PG 15 WC Biophysics SC Biophysics GA FK547 UT WOS:A1991FK54700006 PM 1651120 ER PT J AU PAUL, WE AF PAUL, WE TI INTERLEUKIN-4 - A PROTOTYPIC IMMUNOREGULATORY LYMPHOKINE SO BLOOD LA English DT Review ID CELL-STIMULATORY FACTOR; FACTOR-I INTERLEUKIN-4; RESTING B-CELLS; RECOMBINANT HUMAN INTERLEUKIN-4; SYNTHESIS INDUCED INVITRO; CYTOKINE GENE-CLUSTER; RECEPTOR BETA-CHAIN; T-HELPER SUBSETS; INTERFERON-GAMMA; GROWTH-FACTOR RP PAUL, WE (reprint author), NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N311,BETHESDA,MD 20892, USA. NR 122 TC 711 Z9 720 U1 2 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1991 VL 77 IS 9 BP 1859 EP 1870 PG 12 WC Hematology SC Hematology GA FJ957 UT WOS:A1991FJ95700001 PM 2018830 ER PT J AU PLUDA, JM YARCHOAN, R BRODER, S AF PLUDA, JM YARCHOAN, R BRODER, S TI GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND AZIDOTHYMIDINE IN PATIENTS WITH ACQUIRED-IMMUNODEFICIENCY-SYNDROME - RESPONSE SO BLOOD LA English DT Letter ID HIV-1; VIRUS RP PLUDA, JM (reprint author), NCI,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1991 VL 77 IS 9 BP 2086 EP 2087 PG 2 WC Hematology SC Hematology GA FJ957 UT WOS:A1991FJ95700037 ER PT J AU ALKON, DL AMARAL, DG BEAR, MF BLACK, J CAREW, TJ COHEN, NJ DISTERHOFT, JF EICHENBAUM, H GOLSKI, S GORMAN, LK LYNCH, G MCNAUGHTON, BL MISHKIN, M MOYER, JR OLDS, JL OLTON, DS OTTO, T SQUIRE, LR STAUBLI, U THOMPSON, LT WIBLE, C AF ALKON, DL AMARAL, DG BEAR, MF BLACK, J CAREW, TJ COHEN, NJ DISTERHOFT, JF EICHENBAUM, H GOLSKI, S GORMAN, LK LYNCH, G MCNAUGHTON, BL MISHKIN, M MOYER, JR OLDS, JL OLTON, DS OTTO, T SQUIRE, LR STAUBLI, U THOMPSON, LT WIBLE, C TI LEARNING AND MEMORY SO BRAIN RESEARCH REVIEWS LA English DT Article DE LONG-TERM POTENTIATION; AMYGDALA; SYNAPTIC PLASTICITY; HIPPOCAMPUS; APLYSIA; CALCIUM; TEMPORAL LOBE; NEURAL NETWORK; VISUAL CORTEX ID LONG-TERM POTENTIATION; PROTEIN-KINASE-C; NICTITATING-MEMBRANE RESPONSE; RABBIT HIPPOCAMPAL-NEURONS; THETA-PATTERN STIMULATION; AFFINITY CHOLINE UPTAKE; DENTATE GRANULE CELLS; CA1 PYRAMIDAL NEURONS; KITTEN VISUAL-CORTEX; MEDIAL SEPTAL AREA C1 SALK INST, SAN DIEGO, CA 92186 USA. BROWN UNIV, CTR NEURAL SCI, PROVIDENCE, RI 02912 USA. YALE UNIV, DEPT PSYCHOL, NEW HAVEN, CT 06520 USA. NORTHWESTERN UNIV, SCH MED, DEPT CELL MOLEC & STRUCT BIOL, CHICAGO, IL 60611 USA. WELLESLEY COLL, DEPT BIOL SCI, WELLESLEY, MA 02181 USA. UNIV CALIF IRVINE, CTR NEUROBIOL LEARNING & MEMORY, IRVINE, CA 92717 USA. UNIV ARIZONA, DEPT PSYCHOL, TUCSON, AZ 85724 USA. NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD 21218 USA. RI Olds, James/D-2867-2011; Thompson, Lucien/F-3496-2012; OI Thompson, Lucien/0000-0001-8878-0221; Disterhoft, John/0000-0002-8817-7913 NR 178 TC 109 Z9 114 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD MAY-AUG PY 1991 VL 16 IS 2 BP 193 EP 220 DI 10.1016/0165-0173(91)90005-S PG 28 WC Neurosciences SC Neurosciences & Neurology GA GK118 UT WOS:A1991GK11800005 PM 1760656 ER PT J AU HENNINGFIELD, JE COHEN, C SLADE, JD AF HENNINGFIELD, JE COHEN, C SLADE, JD TI IS NICOTINE MORE ADDICTIVE THAN COCAINE SO BRITISH JOURNAL OF ADDICTION LA English DT Article ID DRUG; TOBACCO AB Is nicotine more additive than cocaine? That claim is increasingly in vogue, often supported by data showing the high likelihood of progression to daily tobacco use following experimentation and the high percentage of cigarette smokers, compared with cocaine users who appear addicted. In the context of criteria for addiction or dependence presented by the World Health Organization, the American Psychiatric Association, and the US Surgeon General, we consider several lines of evidence, including patterns of use, mortality, physical dependence potential, and pharnacologic addiction liability measures. Within each line of evidence, we compare nicotine with cocaine. We conclude that on the current evidence nicotine cannot be considered more addicting than cocaine. Both are highly addicting drugs for which patterns of use and the development of dependence are strongly influenced by factors such as availability, price, social pressures, and regulations, as well as certain pharmacologic characteristics. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. UNIV MED & DENT NEW JERSEY,DEPT MED,NEW BRUNSWICK,NJ 08903. RP HENNINGFIELD, JE (reprint author), NIDA,ADDIC RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 27 TC 51 Z9 51 U1 0 U2 6 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD MAY PY 1991 VL 86 IS 5 BP 565 EP 569 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA FN476 UT WOS:A1991FN47600017 PM 1859920 ER PT J AU GLYNN, TJ AF GLYNN, TJ TI COMPREHENSIVE APPROACHES TO TOBACCO USE CONTROL SO BRITISH JOURNAL OF ADDICTION LA English DT Article ID SMOKING CESSATION; ESSENTIAL ELEMENTS; RANDOMIZED TRIAL; INTERVENTION; PHYSICIANS; QUIT AB This essay suggests approaches to two issues of importance to the future of tobacco use control research. First, there is need to identify those areas of tobacco use prevention and cessation research which have evolved to the point where additional investigation would only bring incremental gains. The reduction potential of this research should then be consolidated by applying existing, effective interventions widely and systematically. Conversely, there is need to identify those areas in which additional research is necessary. Second, the most logical way to reach agreement on those areas which are ready to move from research to applications-of-research is, with the co-operation and advice of the research community, through the large funding organizations which have supported this research over the past 2 decades. It is these organizations which, once the most effective interventions are identified, are capable of supporting the centrally-planned, consensus-driven, comprehensive approaches to tobacco use control which will be necessary to continued success in reducing tobacco-related morbidity and mortality in the industrialized world and to begin addressing the growing problems of tobacco use in the developing world. RP NCI, SMOKING TOBACCO & CANC PROGRAM, EXECTUT PLAZA N 320, BETHESDA, MD 20892 USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU CARFAX PUBLISHING-TAYLOR & FRANCIS GROUP PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0952-0481 J9 BRIT J ADDICT PD MAY PY 1991 VL 86 IS 5 BP 631 EP 635 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA FN476 UT WOS:A1991FN47600029 PM 1859931 ER PT J AU PALLI, D BIANCHI, S CIPRIANI, F DUCA, P AMOROSI, A AVELLINI, C RUSSO, A SARAGONI, A TODDE, P VALDES, E VINDIGNI, C BLOT, WJ FRAUMENI, JF BUIATTI, E AF PALLI, D BIANCHI, S CIPRIANI, F DUCA, P AMOROSI, A AVELLINI, C RUSSO, A SARAGONI, A TODDE, P VALDES, E VINDIGNI, C BLOT, WJ FRAUMENI, JF BUIATTI, E TI REPRODUCIBILITY OF HISTOLOGIC CLASSIFICATION OF GASTRIC-CANCER SO BRITISH JOURNAL OF CANCER LA English DT Article AB A panel review of histologic specimens was carried out as part of a multi-centre case-control study of gastric cancer (GC) and diet. Comparisons of diagnoses of 100 GCs by six pathologists revealed agreement in histologic classification for about 70-80% of the cancers. Concordance was somewhat higher when using the Lauren rather than the Ming or World Health Organization classification systems. Histologic types from reading biopsy tissue agreed with those derived from surgical specimens for 65-75% of the 100 tumours. Intra-observer agreement in histologic classification, assessed by repeat readings up to 3 years apart by one pathologist, was 95%. The findings indicate that, although overall concordance was good, it is important to standardise diagnoses in multi-centre epidemiologic studies of GC by histologic type. C1 CTR STUDIO & PREVENZ ONCOL,EPIDEMIOL UNIT,VIALE VOLTA 171,I-50131 FLORENCE,ITALY. UNIV FLORENCE,POLICLIN CAREGGI,IST ANAT PATOL,I-50134 FLORENCE,ITALY. UNIV SIENA,IST ANAT PATOL,I-53100 SIENA,ITALY. UNIV MILAN,IST BIOMETRIA & STAT,I-20133 MILAN,ITALY. OSPED IMOLA,SERV ANAT PATOL,I-40026 IMOLA,ITALY. OSPED MORGAGNI PIERANTONI,SERV ANAT PATOL,I-47010 FORLI,ITALY. OSPED BROTZU,SERV ANAT PATOL,I-09100 CAGLIARI,ITALY. OSPED SS TRINITA,SERV ANAT PATOL,I-09100 CAGLIARI,ITALY. NCI,BETHESDA,MD 20892. OI PALLI, Domenico/0000-0002-5558-2437 NR 7 TC 30 Z9 30 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1991 VL 63 IS 5 BP 765 EP 768 DI 10.1038/bjc.1991.171 PG 4 WC Oncology SC Oncology GA FM915 UT WOS:A1991FM91500021 PM 2039701 ER PT J AU WEISSMAN, G AF WEISSMAN, G TI WORKING WITH PREGNANT-WOMEN AT HIGH-RISK FOR HIV-INFECTION - OUTREACH AND INTERVENTION SO BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article; Proceedings Paper CT SYMP ON PREGNANCY AND SUBSTANCE ABUSE : PERSPECTIVES AND DIRECTIONS CY MAR 22, 1990 CL NEW YORK ACAD MED, NEW YORK, NY SP NEW YORK ACAD MED, COMM PUBLIC HLTH, MED & HLTH RES ASSOC NEW YORK CITY, COLUMBIA UNIV, SCH PUBLIC HLTH, NEW YORK COUNTY MED SOC, MATERNAL & CHILD HLTH PROGRAM, GREATER NEW YORK MARCH DIMES, AGENDA CHILDREN TOMORROW HO NEW YORK ACAD MED RP WEISSMAN, G (reprint author), NIDA,DIV APPL RES,COMMUNITY RES BRANCH,ROCKVILLE,MD, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NEW YORK ACAD MEDICINE PI NEW YORK PA 1216 FIFTH AVE, NEW YORK, NY 10029 SN 0028-7091 J9 B NEW YORK ACAD MED JI Bull. N. Y. Acad. med. PD MAY-JUN PY 1991 VL 67 IS 3 BP 291 EP 300 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA FQ294 UT WOS:A1991FQ29400010 PM 1868280 ER PT J AU WEISSMAN, G MITCHELL, J ERIC, K JAINCHILL, N CABRERA, D HALE, L MINKOFF, H BROWN, L AF WEISSMAN, G MITCHELL, J ERIC, K JAINCHILL, N CABRERA, D HALE, L MINKOFF, H BROWN, L TI WORKSHOP ON RESIDENTIAL AND OUTPATIENT TREATMENT MODALITIES SO BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Editorial Material RP WEISSMAN, G (reprint author), NIDA,DIV APPL RES,COMMUNITY RES BRANCH,ROCKVILLE,MD, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD MEDICINE PI NEW YORK PA 1216 FIFTH AVE, NEW YORK, NY 10029 SN 0028-7091 J9 B NEW YORK ACAD MED JI Bull. N. Y. Acad. med. PD MAY-JUN PY 1991 VL 67 IS 3 BP 311 EP 314 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA FQ294 UT WOS:A1991FQ29400014 PM 1868284 ER PT J AU PETTIT, GR SENGUPTA, D HERALD, CL SHARKEY, NA BLUMBERG, PM AF PETTIT, GR SENGUPTA, D HERALD, CL SHARKEY, NA BLUMBERG, PM TI SYNTHETIC CONVERSION OF BRYOSTATIN-2 TO BRYOSTATIN-1 AND RELATED BRYOPYRANS SO CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE LA English DT Article DE BRYOSTATIN 2-]1; SELECTIVE CONVERSION; BRYOSTATINS-4 AND 5; PIVALATES ID PROTEIN KINASE-C; ANTI-NEOPLASTIC AGENTS; ANTINEOPLASTIC AGENTS; BUGULA-NERITINA; MARINE; ACTIVATOR; RECEPTOR; BRYOZOA; CELLS AB Bryostatin 2 (1a) has been converted to bryostatin 1 (1e) and bryostatin 12 (1i) by a selective protection and deprotection involving the C-26 hydroxyl group. The new bryostatins 1g, 1k, and 1m were also prepared starting from bryostatin 2. The C-7 substituents of natural bryostatins 4 and 5 were revised from isovalerate --> pivalate employing comparative H-1 and C-13 NMR studies of the semi-synthetic bryostatins 1k and 1m and the natural products. C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NCI,LCCTP,MOLEC MECH TUMOR PROMOT SECT,BETHESDA,MD 20892. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,INST SPACE SCI,TEMPE,AZ 85287, USA. NR 30 TC 19 Z9 19 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4042 J9 CAN J CHEM JI Can. J. Chem.-Rev. Can. Chim. PD MAY PY 1991 VL 69 IS 5 BP 856 EP 860 DI 10.1139/v91-126 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA FP799 UT WOS:A1991FP79900014 ER PT J AU YUN, JCH OHMAN, KP GILL, JR KEISER, H AF YUN, JCH OHMAN, KP GILL, JR KEISER, H TI EFFECTS OF PROSTAGLANDINS, CAMP, AND CHANGES IN CYTOSOLIC CALCIUM ON PLATELET-AGGREGATION INDUCED BY A THROMBOXANE-A2 MIMIC (U46619) SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article DE THROMBOXANE; CYTOSOLIC CALCIUM; PLATELET AGGREGATION; PROSTAGLANDINS; EGTA; VERAPAMIL; 8-(DIETHYLAMINO)-OCTYL-3,4,5-TRIMETHOXYBENZOATE HYDROCHLORIDE ID HUMAN-BLOOD PLATELETS; IIB-IIIA COMPLEX; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; SIGNAL TRANSDUCTION; CA2+ ANTAGONIST; PROTEIN-KINASE; CA-2+; STIMULATION; ACTIVATION; PHOSPHORYLATION AB The effects of U46619, a thromboxane mimic, on cytosolic Ca2+ concentration and platelet aggregation were determined in human platelets. Cytosolic Ca2+ concentration was determined by Quin-2 fluorescence and platelet aggregation quantitated with an aggregometer. Addition of U46619 (1 X 10(-7) M) to the platelet suspension produced a rapid increase in cytosolic Ca2+ and platelet aggregation. Pretreatment of platelets with EGTA (3 X 10(-3) M), verapamil (5 X 10(-4) M), a calcium entry blocker, or 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (1 X 10(-3) M), an inhibitor of intracellular Ca2+ release, either blunted or markedly delayed the rate, but not the magnitude, of increase in cytosolic Ca2+ and prevented platelet aggregation by U46619. Pretreatment of platelets with prostaglandin I2 (PGI2) (5 X 10(-8) M), PGD2 (5 X 10(-8) M), PGE1 (5 X 10(-8) M), PGF2-alpha (1 X 10(-5) M), dibutyryl cAMP (5 X 10(-3) M), or forskolin (1 X 10(-6) M) prevented both the increase in cytosolic Ca2+ and the associated platelet aggregation induced by U46619. These data suggest that U46619 may induce platelet aggregation through an increase in cytosolic Ca2+, and that both Ca2+ entry and its release from intracellular storage sites probably contribute to the increase in cytosolic Ca2+. Furthermore, the rate of the increase in cytosolic Ca2+ concentration, as well as the magnitude of the increase, appear to be critical for platelet aggregation induced by U46619. Our data are consistent with the hypothesis that PGs inhibit U46619-induced platelet aggregation by preventing the increase in cytosolic Ca2+, and that these effects may be mediated via an increase in cAMP, since they were induced by PGs and cAMP. C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. RP YUN, JCH (reprint author), HOWARD UNIV,COLL MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20059, USA. FU NIGMS NIH HHS [SO6GM08016] NR 34 TC 9 Z9 9 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD MAY PY 1991 VL 69 IS 5 BP 599 EP 604 PG 6 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA FL265 UT WOS:A1991FL26500008 PM 1650650 ER PT J AU DUBNER, R AF DUBNER, R TI BASIC MECHANISMS OF PAIN ASSOCIATED WITH DEEP TISSUES .1. INTRODUCTORY-REMARKS SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Editorial Material ID SPINAL-CORD; DORSAL HORN; VISCERAL INPUTS; LAMINA-I; RAT; NOCICEPTION; STIMULI AB There are important differences in pain arising from deep tissues in comparison to cutaneous pain. These differences can be partially explained by the unique organization of nociceptive systems activated by stimulation of muscle, joint, or viscera. Recent evidence also indicates that stimulation of deep tissues can produce long-lasting changes in central nervous system excitability and, therefore, may play a prominent role in persistent or chronic pain conditions. These findings have important implications for the treatment of chronic deep tissue pain conditions. RP DUBNER, R (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892, USA. NR 19 TC 18 Z9 19 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD MAY PY 1991 VL 69 IS 5 BP 607 EP 609 PG 3 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA FL265 UT WOS:A1991FL26500010 PM 1863910 ER PT J AU XUAN, XZ SCHATZKIN, A MAO, BL TAYLOR, PR LI, JY TANGREA, J YAO, SX QIAO, YL GIFFEN, C MCADAMS, M AF XUAN, XZ SCHATZKIN, A MAO, BL TAYLOR, PR LI, JY TANGREA, J YAO, SX QIAO, YL GIFFEN, C MCADAMS, M TI FEASIBILITY OF CONDUCTING A LUNG-CANCER CHEMOPREVENTION TRIAL AMONG TIN MINERS IN YUNNAN, PEOPLES-REPUBLIC-OF-CHINA SO CANCER CAUSES & CONTROL LA English DT Article DE CARCINOGENS; CHEMOPREVENTION TRIAL; CHINA; MICRONUTRIENTS; MINERS; PEOPLES-REPUBLIC-OF-CHINA AB Tin miners in Yunnan Province in southern China have an extremely high rate of lung cancer, more than one percent per year among those at 'high risk' (40+ years old, with 10+ years of underground mining and/or smelting experience). The extraordinary lung cancer rates result from combined exposure to radon, arsenic, and tobacco smoking (cigarettes and/or bamboo water pipe). A study to determine the feasibility of conducting a large-scale, lung-cancer chemoprevention trial was conducted in 1986 among currently employed or retired miners from the Yunnan Tin Corporation in the city of Gejiu. The study was designed to answer four questions: (i) Could potentially eligible miners be identified and recruited? (ii) Could intervention agents be shipped successfully from the United States to the study area and be appropriately distributed? (iii) Would miners adequately adhere to the study protocol and comply with the intervention regimen? (iv) Could potential adverse effects be monitored and documented? The six-month feasibility study yielded affirmative answers to each of these questions. A roster of over 7,000 high-risk miners was complied. Four agents (vitamin A, 25,000 IU; beta-carotene, 50 mg; vitamin E, 800 IU; and selenium, 400-mu-g) were administered daily with placebos to 350 miners according to a 2(4) factorial design. Adherence, assessed by pill counts and serum micronutrient levels, was approximately 90 percent. The findings from this preliminary study indicate that a full-scale, lung-cancer chemoprevention trial in this population is feasible. C1 NCI,9000 ROCKVILLE PIKE,EPN 211,BETHESDA,MD 20892. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 9 Z9 9 U1 0 U2 5 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1991 VL 2 IS 3 BP 175 EP 182 DI 10.1007/BF00056211 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA FP423 UT WOS:A1991FP42300005 PM 1873448 ER PT J AU BUCHER, JR HUFF, JE JOKINEN, MP HASEMAN, JK STEDHAM, M CHOLAKIS, JM AF BUCHER, JR HUFF, JE JOKINEN, MP HASEMAN, JK STEDHAM, M CHOLAKIS, JM TI INHALATION OF TETRANITROMETHANE CAUSES NASAL PASSAGE IRRITATION AND PULMONARY CARCINOGENESIS IN RODENTS SO CANCER LETTERS LA English DT Article ID RAS PROTOONCOGENE; LUNG-TUMORS; ACTIVATION; RATS AB Fischer 344 rats and B6C3F1 mice were exposed for 2 years to vapors of tetranitromethane at concentrations below (0.5 ppm) and slightly above (2 or 5 ppm) the current U.S. recommended occupational exposure limit. Under the conditions of exposure of 6 h/day, 5 days/week, tetranitromethane was found to cause mild irritation and hyperplastic lesions in the nasal passages, but no nasal cavity neoplasms were observed. In contrast, nearly all animals exposed to the higher TNM concentrations, and the majority of animals exposed to the lower concentrations developed alveolar/bronchiolar adenoma or carcinoma; squamous cell neoplasms of the lung also occurred in exposed rats. The extent of the lung tumor response, and the low concentrations of tetranitromethane required for this response, are unprecedented in National Toxicology Program (NTP) studies. C1 MIDWEST RES INST,KANSAS CITY,MO 64110. PATHOL ASSOCIATES INC,FREDERICK,MD 21701. RP BUCHER, JR (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 20 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAY 1 PY 1991 VL 57 IS 2 BP 95 EP 101 DI 10.1016/0304-3835(91)90201-R PG 7 WC Oncology SC Oncology GA FL954 UT WOS:A1991FL95400002 PM 1851054 ER PT J AU LANGSTEIN, HN DOHERTY, GM FRAKER, DL BURESH, CM NORTON, JA AF LANGSTEIN, HN DOHERTY, GM FRAKER, DL BURESH, CM NORTON, JA TI THE ROLES OF GAMMA-INTERFERON AND TUMOR-NECROSIS-FACTOR-ALPHA IN AN EXPERIMENTAL RAT MODEL OF CANCER CACHEXIA SO CANCER RESEARCH LA English DT Article ID FACTOR CACHECTIN; PASSIVE-IMMUNIZATION; ANOREXIA; TOXICITY; MICE; TNF; INTERLEUKIN-1; MACROPHAGES; TOLERANCE; ENDOTOXIN AB Administration of repetitive sublethal doses of either recombinant human tumor necrosis factor (TNF) or recombinant murine gamma-interferon (IFN) to non-tumor-bearing (NTB) rats caused a significant decline in food intake and body weight. After 3 days rats became resistant to the anorectic and weight loss effects of TNF but maintained persistent diminished food intake and diminished body weight gain while receiving recombinant murine IFN. Passive immunization against recombinant rat gamma-interferon allowed cachectic tumor-bearing (TB) rats to eat more food, have a lesser decline in body weight, live longer, and tolerate larger tumors than similar TB rats given nonspecific control antibody. TB rats treated with an antisera to recombinant murine TNF, which was 100% protective when given to NTB rats 6 h before a lethal endotoxin challenge, did not differ significantly from TB rats treated with control antibody with respect to food intake, body weight, survival, or tumor size. Serum levels of TNF or IFN were not detectable in cachectic tumor-bearing rats. The data indicate that the administration of exogenous IFN can simulate cachexia in NTB rats and that passive immunization against it can partially reverse the cachectic changes associated with cancer and prolong survival. These findings suggest that gamma-interferon may be an important mediator of cachexia in this rat tumor model. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NR 31 TC 98 Z9 100 U1 1 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 MAY 1 PY 1991 VL 51 IS 9 BP 2302 EP 2306 PG 5 WC Oncology SC Oncology GA FJ821 UT WOS:A1991FJ82100010 PM 1901758 ER PT J AU LEONE, A MCBRIDE, OW WESTON, A WANG, MG ANGLARD, P CROPP, CS GOEPEL, JR LIDEREAU, R CALLAHAN, R LINEHAN, WM REES, RC HARRIS, CC LIOTTA, LA STEEG, PS AF LEONE, A MCBRIDE, OW WESTON, A WANG, MG ANGLARD, P CROPP, CS GOEPEL, JR LIDEREAU, R CALLAHAN, R LINEHAN, WM REES, RC HARRIS, CC LIOTTA, LA STEEG, PS TI SOMATIC ALLELIC DELETION OF NM23 IN HUMAN CANCER SO CANCER RESEARCH LA English DT Note ID INSITU HYBRIDIZATION; DNA-SEQUENCES; GENE; CHROMOSOME-17; LOCALIZATION AB Tumor progression to the metastatic phenotype is accompanied in certain cell types by reduced expression of the nm23 gene. We have localized human nm23-H1 to chromosome 17 by somatic cell hybrid analysis. Regional localization in the CEPH database and in situ hybridization is reported. Somatic allelic deletion of nm23-H1 was observed in human breast, renal, colorectal, and lung carcinoma DNA samples, as compared to DNA from matched normal tissues. A homozygous deletion of nm23-H1 was observed in a lymph node metastasis of a colorectal carcinoma, indicating that nm23-H1 can be recessively inactivated. The data identify nm23-H1 as a novel, independent locus for allelic deletion in human cancer, a characteristic shared with previously described suppressor genes. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD S10 2RX,S YORKSHIRE,ENGLAND. CTR RENE HUGOENIN,F-92211 ST CLOUD,FRANCE. RP LEONE, A (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 20 TC 180 Z9 188 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 MAY 1 PY 1991 VL 51 IS 9 BP 2490 EP 2493 PG 4 WC Oncology SC Oncology GA FJ821 UT WOS:A1991FJ82100040 PM 2015608 ER PT J AU CHIARODO, A AF CHIARODO, A TI NATIONAL-CANCER-INSTITUTE ROUND-TABLE ON PROSTATE-CANCER - FUTURE-RESEARCH DIRECTIONS SO CANCER RESEARCH LA English DT Editorial Material RP CHIARODO, A (reprint author), NCI,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20892, USA. NR 0 TC 148 Z9 148 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1991 VL 51 IS 9 BP 2498 EP 2505 PG 8 WC Oncology SC Oncology GA FJ821 UT WOS:A1991FJ82100042 PM 2015610 ER PT J AU POIRIER, MC FULLERTON, NF KINOUCHI, T SMITH, BA BELAND, FA AF POIRIER, MC FULLERTON, NF KINOUCHI, T SMITH, BA BELAND, FA TI COMPARISON BETWEEN DNA ADDUCT FORMATION AND TUMORIGENESIS IN LIVERS AND BLADDERS OF MICE CHRONICALLY FED 2-ACETYLAMINOFLUORENE SO CARCINOGENESIS LA English DT Article ID DOSE-RESPONSE; MOLECULAR DOSIMETRY; RAT-LIVER; CARCINOGENESIS; INDUCTION; CELLS; 4-(N-METHYL-N-NITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; DIETHYLNITROSAMINE; NEOPLASIA; THYMOMAS AB Female BALB/c mice continuously fed 2-acetylaminofluorene (AAF) develop liver and bladder tumors. The incidence of liver tumors is linearly related to the carcinogen concentration in the diet, while the tumor response in the bladder is markedly non-linear. In the current experiments, liver and bladder DNA adducts were measured in female BALB/c mice fed several different concentrations of AAF for 28 days. The adduct concentrations were then compared to the previously reported incidences of neoplastic and preneoplastic lesions in these tissues. In initial experiments, mice were fed either 30 or 150 mg [ring-H-3]AAF/kg diet for 21 days. Liver DNA adducts were identified by HPLC, which indicated the presence of one major adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF). This adduct was also the major product detected by P-32-postlabeling in liver and bladder DNA from mice fed the same concentrations of AAF for 28 days. Radioimmunoassays, conducted with an antibody specific for dG-C8-AF, showed that steady-state concentrations of dG-C8-AF were obtained at 28 days of AAF feeding; thus, this time point was used to determine the relationship between the dose of AAF and the adduct levels. In mice fed nine concentrations of AAF (5-150 mg AAF/kg diet), the adduct concentrations after 28 days of feeding were linearly related to dose in both the liver and bladder, with the adduct concentration being approximately 3-fold greater in the bladder. These results indicate that a linear correlation exists between the hepatic concentration of dG-C8-AF and the liver tumor incidence. In the bladder however, a linear relationship was not observed, which suggests that additional tissue-specific factors, such as toxicity, are essential components for tumorigenesis in this tissue. C1 NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. RP POIRIER, MC (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B25,BETHESDA,MD 20892, USA. NR 31 TC 67 Z9 68 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1991 VL 12 IS 5 BP 895 EP 900 DI 10.1093/carcin/12.5.895 PG 6 WC Oncology SC Oncology GA FL733 UT WOS:A1991FL73300023 PM 2029755 ER PT J AU SCHUT, HAJ SNYDERWINE, EG ZU, HX THORGEIRSSON, SS AF SCHUT, HAJ SNYDERWINE, EG ZU, HX THORGEIRSSON, SS TI SIMILAR PATTERNS OF DNA ADDUCT FORMATION OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE IN THE FISCHER-344 RAT, CDF1 MOUSE, CYNOMOLGUS MONKEY AND SALMONELLA-TYPHIMURIUM SO CARCINOGENESIS LA English DT Note ID HUMAN-LIVER MICROSOMES; METABOLIC-ACTIVATION; MUTAGENIC ACTIVATION; TISSUE DISTRIBUTION; BROILED SARDINE; BEEF EXTRACT; BINDING; CARCINOGENICITY; MICE; 2-HYDROXYAMINO-3-METHYLIMIDAZOLO<4,5-F>QUINOLINE AB 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is a known liver carcinogen in the Fischer 344 rat, the CDF1 mouse and in the cynomolgus monkey. Using P-32-postlabeling assays, we compared IQ-DNA adduct formation in the liver of IQ-treated Fischer 344 rats, CDF1 mice and cynomolgus monkeys with that in Salmonella typhimurium (strain TA98) incubated with IQ (in the presence of a liver S9 activating system) or N-hydroxy-IQ, and with that in calf thymus DNA reacted with IQ (in the presence of a liver S9 activating system) or N-hydroxy-IQ. Up to five adducts could be detected, the pattern of which was identical in all cases. The major adduct co-chromatographed with standard N-(deoxyguanosin-8-yl)-IQ in all cases and comprised 54.7-82.8% of the total. The four minor adducts were not identified. It is concluded that N-(deoxyguanosin-8-yl)-IQ is the major IQ-DNA adduct under all experimental conditions and that the pattern of N-hydroxy-IQ-DNA adducts is identical to that found in the liver of animals exposed to IQ, and to that found after reacting IQ with DNA in the presence of a liver S9 activating system. Thus, N-hydroxylation of IQ is a critical step in the formation of IQ-DNA adducts. C1 NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. RP SCHUT, HAJ (reprint author), MED COLL OHIO,DEPT PATHOL,HLTH EDUC BLDG,3000 ARLINGTON AVE,TOLEDO,OH 43614, USA. FU NCI NIH HHS [R01 CA47484] NR 30 TC 39 Z9 39 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1991 VL 12 IS 5 BP 931 EP 934 DI 10.1093/carcin/12.5.931 PG 4 WC Oncology SC Oncology GA FL733 UT WOS:A1991FL73300030 PM 2029759 ER PT J AU CARRARO, R LI, ZH JOHNSON, JE GREGERMAN, RI AF CARRARO, R LI, ZH JOHNSON, JE GREGERMAN, RI TI ISLETS OF PREADIPOCYTES HIGHLY COMMITTED TO DIFFERENTIATION IN CULTURES OF ADHERENT RAT ADIPOCYTES - LIGHT-MICROSCOPIC AND ELECTRON-MICROSCOPIC OBSERVATIONS SO CELL AND TISSUE RESEARCH LA English DT Article DE PREADIPOCYTES; ADIPOCYTE PRECURSOR CELLS; ADIPOSE TISSUE; DIFFERENTIATION-CELL CULTURES; ULTRASTRUCTURE; RAT (FISCHER-344) ID UNILOCULAR FAT-CELLS; ADIPOSE-TISSUE; PRECURSOR AB Cultures of adherent mature adipocytes, obtained from collagenase-digests of adipose tissue of the rat, invariably contain rapidly proliferating, fibroblast-like cells despite the washing and centrifugation procedures employed during isolation of the fat cells. Such spindle-like cells originate from low-density structures, which we term "islets", that are present, together with the mature adipocytes, in the floating layer of the digest of adipose tissue. Islets are found in preparations from adult (3-4 months old) as well as aging (17-24 months old) rats. By light- and electron microscopy, the islets appear as clusters of closely associated cells containing a variable amount of lipid-like material. Cells of endothelial or pericytic origin are also present in the islets. Within a few hours of culture, the islets give rise to those spindle-like cells that have been seen to proliferate in the cultures. By 36-48 hours, such cells begin to accumulate lipid droplets and, by 150 hours, assume the morphology of small mature adipocytes (diameter 20-35-mu-m) with a large central lipid droplet. The pattern of differentiation of these cells recalls that of preadipocytes derived from the stromal-vascular fraction of adipose tissue digests. Nonetheless, the extent and rapidity of their adipose conversion, as well as the culture conditions necessary for differentiation, are different and suggest that these cells are a substantially uniform subpopulation of adipocyte-precursor cells highly committed to differentiation. C1 FRANCIS SCOTT KEY MED CTR,DEPT MED,4940 EASTERN AVE,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. STANFORD RES INST,STANFORD,CA 94305. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21224. NR 21 TC 7 Z9 15 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD MAY PY 1991 VL 264 IS 2 BP 243 EP 251 DI 10.1007/BF00313961 PG 9 WC Cell Biology SC Cell Biology GA FJ458 UT WOS:A1991FJ45800006 PM 1878944 ER PT J AU MAVROTHALASSITIS, GJ PAPAS, TS AF MAVROTHALASSITIS, GJ PAPAS, TS TI POSITIVE AND NEGATIVE FACTORS REGULATE THE TRANSCRIPTION OF THE ETS2 GENE VIA AN ONCOGENE-RESPONSIVE-LIKE UNIT WITHIN THE ETS2 PROMOTER REGION SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID LONG TERMINAL REPEAT; DNA-BINDING; EXPRESSION; PROTEIN; ACTIVATION; SEQUENCE; PROTOONCOGENE; VIRUS; CELLS AB The DNA-protein interactions in the ETS2 promoter have been studied. Three distinct sequence motifs have been identified, each of which interacts with at least two distinctive protein complexes. The GC motif, possessing mirror symmetry, interacts with two ubiquitously identifiable complexes (S and S2); the PEA3 motif interacts with a ubiquitous (H1) and a tissue-specific (H3) complex; the H2 (an AP1-like) motif interacts also with a ubiquitous (H2a) and a tissue-specific (H2b) complex. Mutational analysis and correlation of the presence of defined complexes with the ETS2 mRNA levels indicate that the S, S2, H1, and H2b complexes have positive effects on ETS2 transcription, whereas the H3 and H2a have negative effects. The organization of the PEA3 with the AP1-like motif in the ETS2 promoter resembles the oncogene-responsive unit previously identified in the polyoma virus enhancer region. Our data suggest that cooperation between these two motifs is vital for ETS2 promoter function. RP MAVROTHALASSITIS, GJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. NR 28 TC 23 Z9 23 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1991 VL 2 IS 5 BP 215 EP 224 PG 10 WC Cell Biology SC Cell Biology GA FL349 UT WOS:A1991FL34900001 PM 1888697 ER PT J AU REED, JC YUM, S CUDDY, MP TURNER, BC RAPP, UR AF REED, JC YUM, S CUDDY, MP TURNER, BC RAPP, UR TI DIFFERENTIAL REGULATION OF THE P72-74 RAF-1 KINASE IN 3T3 FIBROBLASTS EXPRESSING RAS OR SRC ONCOGENES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TRANSFORMED FIBROBLASTS; SIGNAL TRANSDUCTION; GROWTH-FACTOR; PROTEIN; PHOSPHORYLATION; ACTIVATION; SUBSTRATE; PROTOONCOGENE; CELLS AB The c-raf-1 protooncogene encodes a p72-74 serine/threonine-specific kinase that has been implicated in growth factor-mediated signal transduction and malignant transformation. Here, we compared the effects of Ha-c-ras and v-src oncogenes on the regulation of p72-74 RAF-1 kinase in NIH3T3 cells. In both serum-starved and platelet-derived growth factor-treated v-src-transformed cells, the RAF-1 kinase was constitutively activated, displaying characteristic retarded mobility in electrophoretic gels and elevated activity in in vitro kinase assays. In contrast, the RAF-1 protein from quiescent ras-transformed cells did not exhibit constitutively shifted gel mobility or elevated kinase activity but did respond normally with regard to platelet-derived growth factor- and phorbol myristate acetate-induced changes in p72-74 RAF-1 phosphorylation and kinase activity. 3T3 cells transformed by ras, however, contained elevated levels of p72-74 RAF-1 protein (as determined by immunoblotting), suggesting an indirect influence on this kinase. Quantitative differences in the levels and subcellular distribution of immunodetectable protein kinase C enzymes did not account for the differences between src- and ras-transformed 3T3 cells with regard to regulation of the RAF kinase. These findings in serum-deprived 3T3 cells demonstrate that expression of a ras oncogene can be insufficient for full activation of the p72-74 RAF-1 kinase, implying necessity for an additional growth factor-mediated stimulus. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP REED, JC (reprint author), UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,231 JOHN MORGAN BLDG,PHILADELPHIA,PA 19104, USA. FU NCI NIH HHS [CA 47956] NR 33 TC 32 Z9 32 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 MAY PY 1991 VL 2 IS 5 BP 235 EP 243 PG 9 WC Cell Biology SC Cell Biology GA FL349 UT WOS:A1991FL34900003 PM 1888699 ER PT J AU ZHOU, R RULONG, S DASILVA, PP VANDEWOUDE, GF AF ZHOU, R RULONG, S DASILVA, PP VANDEWOUDE, GF TI INVITRO AND INVIVO CHARACTERIZATION OF PP39MOS ASSOCIATION WITH TUBULIN SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MATURATION-PROMOTING FACTOR; MOS PROTO-ONCOGENE; CELL-CYCLE; OOCYTE MATURATION; SACCHAROMYCES-CEREVISIAE; CHROMOSOME CONDENSATION; MEIOTIC MATURATION; FISSION YEAST; CDC2 PROTEIN; BETA-TUBULIN AB The product of protooncogene c-mos, pp39mos, is expressed and functions during oocyte maturation. We have previously found that pp39mos is complexed with and phosphorylates tubulin. In addition, part of pp39mos is localized on mitotic spindle and spindle pole regions in c-mos(xe)-transformed NIH/3T3 cells. Here, we further characterized the interaction between pp39mos and tubulin. We show that mos product synthesized in vitro appears in a 500 kD complex and can oligomerize with tubulin in vitro under tubulin polymerization conditions. Moreover, conditions which favor microtubule depolymerization facilitate pp39mos extraction from c-mos(xe)-transformed NIH/3T3 cells. We also show by immunofluorescence and immunoelectron microscopy that pp39mos is localized on microtubules. Thus, in vitro and in vivo the mos product is associated with tubulin and microtubules, respectively. Therefore, the mos product may be involved in the modification of microtubules and formation of the spindle. C1 NCI,DIV CANC BIOL & DIAG,ABL BASIC RES PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC BIOL & DIAG,MATH BIOL LAB,MEMBRANE BIOL SECT,BETHESDA,MD 20892. RP ZHOU, R (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 36 TC 32 Z9 33 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 MAY PY 1991 VL 2 IS 5 BP 257 EP 265 PG 9 WC Cell Biology SC Cell Biology GA FL349 UT WOS:A1991FL34900005 PM 1832292 ER PT J AU HOLTER, W SPIEGEL, AM HOWARD, BH WEBER, S BRANN, MR AF HOLTER, W SPIEGEL, AM HOWARD, BH WEBER, S BRANN, MR TI EXPRESSION OF GTP-BINDING PROTEINS AND PROSTAGLANDIN-E2 RECEPTORS DURING HUMAN T-CELL ACTIVATION SO CELLULAR IMMUNOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION PROTEIN; HUMAN CDNA CLONES; HORMONE RECEPTORS; RAT RETINA; IDENTIFICATION; LYMPHOCYTES; MODULATION; BRAIN C1 NCI,DCDB,MOLEC BIOL LAB,BETHESDA,MD 20892. NIDDK,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. RP HOLTER, W (reprint author), UNIV VIENNA,VIENNA INT RES COOP CTR,INST IMMUNOL,BRUNNERSTR 59,A-1235 VIENNA,AUSTRIA. NR 23 TC 26 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY PY 1991 VL 134 IS 2 BP 287 EP 295 DI 10.1016/0008-8749(91)90303-S PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA FF681 UT WOS:A1991FF68100003 PM 1850662 ER PT J AU SCREPANTI, I MECO, D MORRONE, S GULINO, A MATHIESON, BJ FRATI, L AF SCREPANTI, I MECO, D MORRONE, S GULINO, A MATHIESON, BJ FRATI, L TI INVIVO MODULATION OF THE DISTRIBUTION OF THYMOCYTE SUBSETS - EFFECTS OF ESTROGEN ON THE EXPRESSION OF DIFFERENT T-CELL RECEPTOR V-BETA-GENE FAMILIES IN CD4-, CD8- THYMOCYTES SO CELLULAR IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; ANTIGEN RECEPTOR; CYCLOSPORINE-A; IL-2 RECEPTOR; MONOCLONAL-ANTIBODIES; AUTOIMMUNE-DISEASE; TRANSGENIC MICE; TREATED MICE; BONE-MARROW; THYMUS C1 UNIV LAQUILA,DEPT EXPTL MED,I-67100 LAQUILA,ITALY. NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,BASIC RES SECT,ROCKVILLE,MD 20892. NATL INST CANC RES,1ST BIOTECHNOL SECT,GENOA,ITALY. RP SCREPANTI, I (reprint author), UNIV LA SAPIENZA,DEPT EXPTL MED,324 VIALE REGINA ELENA,I-00161 ROME,ITALY. NR 59 TC 50 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAY PY 1991 VL 134 IS 2 BP 414 EP 426 DI 10.1016/0008-8749(91)90314-2 PG 13 WC Cell Biology; Immunology SC Cell Biology; Immunology GA FF681 UT WOS:A1991FF68100014 PM 1708703 ER PT J AU PELTONEN, K HILTON, BD PATAKI, J LEE, H HARVEY, RG DIPPLE, A AF PELTONEN, K HILTON, BD PATAKI, J LEE, H HARVEY, RG DIPPLE, A TI SPECTROSCOPIC CHARACTERIZATION OF SYN-5-METHYLCHRYSENE 1,2-DIHYDRODIOL 3,4-EPOXIDE DEOXYRIBONUCLEOSIDE ADDUCTS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID DNA ADDUCTS; NUCLEOSIDE ADDUCTS; DIOL-EPOXIDES; MOUSE SKIN; DIHYDRODIOL; ADENINE; 3,4-DIOL-1,2-EPOXIDES; BENZO(C)PHENANTHRENE; BENZOPHENANTHRENE; 5-METHYLCHRYSENE AB Eight deoxyribonucleoside adducts formed from reactions of syn-5-methylchrysene 1,2-dihydrodiol 3,4-epoxide with DNA or with nucleotides were characterized spectroscopically. The adducts arose from both cis and trans opening of the epoxide ring at C4 by the amino group of either deoxyadenosine or deoxyguanosine residues. NMR data indicated that the partially saturated 1,2,3,4-ring of the hydrocarbon residue adopted a boatlike conformation, with the purine residue being disposed pseudoaxially in all adducts. The cis and trans assignments for epoxide ring opening were readily made from coupling constants. Quantitatively, cis adducts predominated over trans adducts in both DNA and nucleotide reactions. Whereas deoxyadenylic acid appeared to trap this dihydrodiol epoxide more efficiently than deoxyguanylic acid, reaction with DNA led to more extensive reaction with deoxyguanosine than with deoxyadenosine residues. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. UNIV CHICAGO,BEN MAY INST,CHICAGO,IL 60637. FU NCI NIH HHS [N01-CO-74102, N01-CO-74101]; NIEHS NIH HHS [ES04266] NR 18 TC 22 Z9 23 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 MAY-JUN PY 1991 VL 4 IS 3 BP 305 EP 310 DI 10.1021/tx00021a008 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA FM137 UT WOS:A1991FM13700009 PM 1912313 ER PT J AU KROEGERKOEPKE, MB SMITH, RH GOODNOW, EA BRASHEARS, J KRATZ, L ANDREWS, AW ALVORD, WG MICHEJDA, CJ AF KROEGERKOEPKE, MB SMITH, RH GOODNOW, EA BRASHEARS, J KRATZ, L ANDREWS, AW ALVORD, WG MICHEJDA, CJ TI 1,3-DIALKYLTRIAZENES - REACTIVE INTERMEDIATES AND DNA ALKYLATION SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID METHYL-N-NITROSOUREA; ALKYLDIAZONIUM IONS; MECHANISM; DECOMPOSITION; SEQUENCE; TRIALKYLTRIAZENES; CARCINOGENESIS; MUTAGENICITY; TRIAZENES; PRODUCTS AB The reactions of calf thymus (ct) DNA with 1,3-dimethyltriazene (DMT), N-methyl-N-nitrosourea (MNU), 1,3-diethyltriazene (DET), N-ethyl-N-nitrosourea (ENU), and 1-ethyl-3-methyltriazene (MET) were studied as a function of concentration of the alkylating agents, of various buffers, and of ionic strength. The amount of alkylation at the 7- and O6-positions of guanine increased linearly with dose over a 10-fold concentration range. The slopes of the DMT and MNU curves were identical as were those of DET and ENU. These data suggest that both types of compounds alkylate DNA via a similar intermediate, presumably the corresponding alkanediazonium ion. MET methylates and ethylates DNA, the amount of each product being a function of the competitive formation of the two diazonium ions possible from MET. The MET product ratios could be reproduced by an appropriate mixture of DET and DMT. The alkylation of DNA by DMT and by MET is very sensitive to ionic strength, to the nature of the buffer, and to the identity of the salt used to balance ionic strength. In general, the reaction is favored by low ionic strength, by amine rather than oxy acid buffers, and by doubly charged inert anions. The alkylation of DNA is inversely proportional to the logarithm of the ionic strength over a wide range. The mutagenic activity of triazenes in Salmonella typhimurium is correlated very well with the ability of the triazenes to form adducts, particularly O6-guanine adducts. Thus, symmetrical 1,3-dialkyltriazenes are mutagens in the order of methyl >> ethyl > butyl = isopropyl, and unsymmetrical 1-alkyl-3-methyltriazenes are mutagens in the order ethyl > butyl > isopropyl. The latter order follows the rate of production of the methanediazonium ion, the most mutagenic of the diazonium ions. C1 NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV,FREDERICK,MD 21702. WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. RP MICHEJDA, CJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74103, N01-CO-74101, N01-CO-74102] NR 32 TC 6 Z9 6 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 MAY-JUN PY 1991 VL 4 IS 3 BP 334 EP 340 DI 10.1021/tx00021a013 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA FM137 UT WOS:A1991FM13700014 PM 1912317 ER PT J AU SATTLER, FR AF SATTLER, FR TI WHO SHOULD RECEIVE CORTICOSTEROIDS AS ADJUNCTIVE TREATMENT FOR PNEUMOCYSTIS-CARINII PNEUMONIA SO CHEST LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PULMONARY KAPOSIS SARCOMA; LONG-TERM CULTURE; PROGNOSTIC FACTORS; INTENSIVE-CARE; THERAPY; CELLS; AIDS C1 UNIV SO CALIF,SCH MED,DEPT MED,INTERDISCIPLINARY AIDS SERV,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,INFECT DIS SECT,LOS ANGELES,CA 90033. NIAID,DIV AIDS,AIDS CLIN TRIALS GRP,COMM OPPORTUNIST INFECT,BETHESDA,MD 20892. NR 19 TC 9 Z9 9 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD MAY PY 1991 VL 99 IS 5 BP 1058 EP 1061 DI 10.1378/chest.99.5.1058 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA FK421 UT WOS:A1991FK42100002 PM 2019155 ER PT J AU YUSUF, S GARG, R AF YUSUF, S GARG, R TI RANDOMIZED TRIALS TO ASSESS THE LONG-TERM EFFECTS OF THERAPIES ON ANGIOGRAPHIC END-POINTS SO CHEST LA English DT Editorial Material ID CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; COLESTIPOL-NIACIN; CLINICAL-TRIALS; ATHEROSCLEROSIS; HYPERCHOLESTEROLEMIA; PROGRESSION; REGRESSION; DRUG RP YUSUF, S (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,BETHESDA,MD 20892, USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD MAY PY 1991 VL 99 IS 5 BP 1243 EP 1247 DI 10.1378/chest.99.5.1243 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA FK421 UT WOS:A1991FK42100039 PM 2019186 ER PT J AU ROWE, WJ AF ROWE, WJ TI A WORLD RECORD MARATHON RUNNER WITH SILENT ISCHEMIA WITHOUT CORONARY ATHEROSCLEROSIS SO CHEST LA English DT Note ID VARIANT ANGINA AB A 62-year-old world record marathon runner was found to have silent ischemia manifested by a very abnormal stress test, whereas at autopsy nine months later, there was virtually no coronary atherosclerosis nor other disease of the coronary microvasculature. However, there was focal fibrosis of the papillary muscles consistent with remote ischemia secondary to possible CV. It is postulated that endurance-related high catecholamine levels might have been responsible. C1 ST VINCENTS MED CTR,DEPT MED,TOLEDO,OH. ST VINCENTS MED CTR,DEPT PATHOL,TOLEDO,OH. MED COLL OHIO,MORSE PHYS HLTH RES CTR,TOLEDO,OH 43699. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 11 TC 21 Z9 22 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD MAY PY 1991 VL 99 IS 5 BP 1306 EP 1308 DI 10.1378/chest.99.5.1306 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA FK421 UT WOS:A1991FK42100061 PM 2019205 ER PT J AU PHARIS, ME LEVIN, VS AF PHARIS, ME LEVIN, VS TI A PERSON TO TALK TO WHO REALLY CARED - HIGH-RISK MOTHERS EVALUATIONS OF SERVICES IN AN INTENSIVE INTERVENTION RESEARCH-PROGRAM SO CHILD WELFARE LA English DT Article ID DEVELOPMENTAL PSYCHOPATHOLOGY C1 UNIV TEXAS,DEPT PSYCHOL,AUSTIN,TX 78712. NIMH,DIV EXTRAMURAL AFFAIRS,ROCKVILLE,MD 20857. NIMH,WILLOUGHBY,CENTENNIAL FELLOW CHILD WELFARE,ROCKVILLE,MD 20857. RP PHARIS, ME (reprint author), UNIV TEXAS,SCH PUBL HLTH,SWB 3 118,AUSTIN,TX 78712, USA. NR 18 TC 17 Z9 17 U1 0 U2 2 PU CHILD WELFARE LEAGUE AMER PI WASHINGTON PA 440 FIRST ST NW, WASHINGTON, DC 20001 SN 0009-4021 J9 CHILD WELFARE JI Child Welf. PD MAY-JUN PY 1991 VL 70 IS 3 BP 307 EP 320 PG 14 WC Family Studies; Social Work SC Family Studies; Social Work GA FK306 UT WOS:A1991FK30600001 PM 2070658 ER PT J AU EPSTEIN, SE CANNON, RO BONOW, RO AF EPSTEIN, SE CANNON, RO BONOW, RO TI EXERCISE TESTING IN PATIENTS WITH MICROVASCULAR ANGINA SO CIRCULATION LA English DT Article DE ANGINA; EXERCISE; MYOCARDIAL ISCHEMIA; TESTING ID NORMAL CORONARY ARTERIOGRAMS; ABNORMAL VASODILATOR RESERVE; LEFT-VENTRICULAR DYSFUNCTION; CHEST PAIN; ARTERY DISEASE; PECTORIS; FLOW; DIPYRIDAMOLE; DIAGNOSIS AB The widespread use of exercise testing for the detection of myocardial ischemia in patients suspected of having coronary artery disease led to the detection of ischemic changes in many subjects who subsequently were found to have angiographically normal epicardial vessels-the false positive response. Such a result is usually interpreted as indicating that the subject's chest pain is of noncardiac origin. For the past several years, we have studied the mechanism of pain resembling angina that occurs in patients with normal epicardial coronary arteries demonstrated by angiography; we believe these studies have shed some light on this problem. Patients with angiographically normal coronary arteries who present because of a history of angina-like pain and/or ischemic changes detected during exercise electrocardiogram testing were evaluated by measuring great cardiac vein flow (under baseline conditions and after cardiac pacing, with and without intravenous administration of ergonovine) and by radionuclide angiography before and during exercise. We found that a substantial number of these subjects showed inadequate coronary vasodilator reserve and had exercise-induced left ventricular dysfunction suggestive of myocardial ischemia. We concluded from our results that there is a distinct clinical syndrome of myocardial ischemia caused by abnormal resistance responses of the prearteriolar coronary microvasculature. We now refer to this syndrome as microvascular angina. In a series of 115 patients with documented microvascular angina, we also found that only 10% had ischemic ST changes with exercise testing (2% of the men and 17% of the women developed ischemic ST segment changes). However, almost 70% of these patients had one or more abnormalities of left ventricular systolic function during exercise as assessed by radionuclide angiography. The low sensitivity of the electrocardiogram for detecting ischemia probably is caused by the ischemia being mild in such patients, and possibly by the existence of a diffuse pattern of ischemia obviating the development of a net electrical vector. We conclude that a positive exercise stress test cannot be considered false positive merely because coronary angiography discloses no epicardial coronary artery disease; the possibility of microvascular angina must be raised and appropriate studies conducted. RP EPSTEIN, SE (reprint author), NHLBI,CARDIOL BRANCH,10-7B14,BETHESDA,MD 20892, USA. NR 32 TC 22 Z9 22 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY PY 1991 VL 83 IS 5 SU S BP 73 EP 76 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FL808 UT WOS:A1991FL80800014 ER PT J AU CANNON, RO SCHENKE, WH QUYYUMI, A BONOW, RO EPSTEIN, SE AF CANNON, RO SCHENKE, WH QUYYUMI, A BONOW, RO EPSTEIN, SE TI COMPARISON OF EXERCISE TESTING WITH STUDIES OF CORONARY FLOW RESERVE IN PATIENTS WITH MICROVASCULAR ANGINA SO CIRCULATION LA English DT Article DE RADIONUCLIDE ANGIOGRAPHY; EXERCISE TESTING; SYNDROME-X ID VASODILATOR RESERVE; CHEST PAIN; SYNDROME-X; PECTORIS; ARTERIES; ARTERIOGRAMS AB Abnormal small coronary artery function may cause limited coronary flow responses to stress, resulting in anginal symptoms and ischemia in some patients with chest pain despite angiographically normal coronary arteries. To assess the exercise hemodynamic correlates of coronary flow abnormalities measured in the cardiac catheterization laboratory, 105 patients with microvascular angina (defined as an increase in coronary vascular resistance during pacing stress after ergonovine administration in the absence of significant epicardial constriction and associated with provocation of the patient's typical chest pain) and 27 patients without any coronary flow abnormality (normal) were analyzed. Of the 105 patients with microvascular angina, 75 had normal electrocardiographic responses to treadmill exercise testing, 22 had ischemic responses, and eight had bundle branch block during exercise. All 27 normal patients had normal electrocardiographic responses to exercise. Patients with ischemic electrocardiographic responses (0 +/- 7%, p < 0.01), and those with bundle branch block (-2 +/- 6%, p < 0.01) had abnormal left ventricular ejection fraction responses to exercise compared with the normal group, who demonstrated an 8 +/- 6% increase in left ventricular ejection fraction by radionuclide angiography during exercise, and microvascular angina patients with a normal electrocardiographic response to exercise, who demonstrated a 5 +/- 7% increase in ejection fraction. Although the microvascular response to ergonovine was no different among the three microvascular angina exercise groups, the administration of dipyridamole caused less coronary vasodilation in those patients with apparently ischemic or bundle branch block responses to exercise compared with those with normal electrocardiograms during exercise. Thus, the limited coronary flow response to dipyridamole may be closely related to the limited ejection fraction response to exercise and the abnormal electrocardiographic response during exercise, presumably reflecting reduced maximum coronary flow available to the myocardium during exercise stress. However, the electrocardiographic and ejection fraction responses to exercise did not separate patients with varying degrees of sensitivity to a vasoconstrictor stimulus such as ergonovine during stress. RP CANNON, RO (reprint author), NHLBI,CARDIOL BRANCH,CARDIOVASC DIAGNOSIS SECT,BLDG 10,ROOM 7B-14,BETHESDA,MD 20892, USA. NR 15 TC 22 Z9 24 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 MAY PY 1991 VL 83 IS 5 SU S BP 77 EP 81 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FL808 UT WOS:A1991FL80800015 ER PT J AU CANNON, RO DILSIZIAN, V OGARA, PT UDELSON, JE SCHENKE, WH QUYYUMI, A FANANAPAZIR, L BONOW, RO AF CANNON, RO DILSIZIAN, V OGARA, PT UDELSON, JE SCHENKE, WH QUYYUMI, A FANANAPAZIR, L BONOW, RO TI MYOCARDIAL METABOLIC, HEMODYNAMIC, AND ELECTROCARDIOGRAPHIC SIGNIFICANCE OF REVERSIBLE TL-201 ABNORMALITIES IN HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Article DE THALLIUM SCINTIGRAPHY; MYOCARDIAL ISCHEMIA; HYPERTROPHIC CARDIOMYOPATHY ID EMISSION COMPUTED-TOMOGRAPHY; PERFUSION ABNORMALITIES; CORONARY FLOW; CHEST PAIN; EXERCISE; VERAPAMIL; REST AB Background. Exercise-induced abnormalities during thallium-201 scintigraphy that normalize at rest frequently occur in patients with hypertrophic cardiomyopathy. However, it is not known whether these abnormalities are indicative of myocardial ischemia. Methods and Results. Fifty patients with hypertrophic cardiomyopathy underwent exercise Tl-201 scintigraphy and, during the same week, measurement of myocardial lactate metabolism and hemodynamics during pacing stress. Thirty-seven patients (74%) had one or more Tl-201 abnormalities that completely normalized after 3 hours of rest; 26 had regional myocardial Tl-201 defects, and 26 had apparent left ventricular cavity dilatation with exercise, with 15 having coexistence of these abnormal findings. Of the 37 patients with reversible Tl-201 abnormalities, 27 (73%) had metabolic evidence of myocardial ischemia during rapid atrial pacing (myocardial lactate extraction of 0 mmol/l or less) compared with four of 13 patients (31%) with normal Tl-201 scans (p < 0.01). Eleven patients had apparent cavity dilatation as their only Tl-201 abnormality; their mean postpacing left ventricular end-diastolic pressure was significantly higher than that of the 13 patients with normal Tl-201 studies (33 +/- 5 versus 21 +/- 10 mm Hg, p < 0.001). There was no correlation between the angiographic presence of systolic septal or epicardial coronary arterial compression and the presence or distribution of Tl-201 abnormalities. Patients with ischemic ST segment responses to exercise had an 80% prevalence rate of reversible Tl-201 abnormalities and a 70% prevalence rate of pacing-induced ischemia. However, 69% of patients with nonischemic ST segment responses had reversible Tl-201 abnormalities, and 55% had pacing-induced ischemia. Conclusions. Reversible Tl-201 abnormalities during exercise stress are markers of myocardial ischemia in hypertrophic cardiomyopathy and most likely identify relatively underperfused myocardium. In contrast, ST segment changes with exercise and systolic compression of coronary arteries on angiography are unreliable markers of inducible myocardial ischemia in hypertrophic cardiomyopathy. Apparent cavity dilatation during Tl-201 scintigraphy may indicate ischemia-related changes in left ventricular filling, with elevation in diastolic pressures and endocardial compression. C1 NHLBI,NUCL CARDIOL SECT,BETHESDA,MD 20892. RP CANNON, RO (reprint author), NHLBI,CARDIOVASC DIAGNOSIS SECT,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 21 TC 120 Z9 123 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 MAY PY 1991 VL 83 IS 5 BP 1660 EP 1667 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FL258 UT WOS:A1991FL25800019 PM 2022023 ER PT J AU MURPHY, E PERLMAN, M LONDON, RE STEENBERGEN, C AF MURPHY, E PERLMAN, M LONDON, RE STEENBERGEN, C TI AMILORIDE DELAYS THE ISCHEMIA-INDUCED RISE IN CYTOSOLIC FREE CALCIUM SO CIRCULATION RESEARCH LA English DT Article DE 5F-BAPTA; CYTOSOLIC FREE CALCIUM; MYOCARDIAL ISCHEMIA; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; NA-H EXCHANGE; NA-CA EXCHANGE ID CHICK HEART-CELLS; PERFUSED RAT-HEART; NA+-H+ EXCHANGE; F-19 NMR; INTRACELLULAR SODIUM; MYOCARDIAL ISCHEMIA; NA+-CA2+ EXCHANGE; MAMMALIAN HEART; CARDIAC-MUSCLE; FERRET HEARTS AB An increase in cytosolic free calcium (Ca(i)) has been shown to occur early during ischemia in perfused rat, ferret, and rabbit hearts. It has been proposed that this increase in Ca(i) may occur as a result of exchange of Na(i) for Ca(o), which occurs as a result of an increase in Na(i) arising from exchange of Na(o) for H+(i). The latter exchange is stimulated by the intracellular acidification that occurs during ischemia. To test this hypothesis, we examined Ca(i), Na(i), ATP, and pH(i) during ischemia in rats in the presence and absence of 1 mM amiloride, a Na-H exchange inhibitor. Ca(i) was measured using F-19 nuclear magnetic resonance (NMR) of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetra-acetic acid (5F-BAPTA)-loaded rat hearts. Na(i) was measured using Na-23 NMR, and the shift reagent 1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetramethylenephosphonate (Tm[DOTP]-5) was used to separate Na(i) and Na(o). ATP and pH were determined from P-31 NMR measurements. During 20 minutes of ischemia, amiloride did not significantly alter the ATP decline but did significantly attenuate the rise in Na(i) and Ca(i). After 20 minutes of ischemia, time-averaged Ca(i) was 1.0 +/- 0.2-mu-M (mean +/- SEM) in amiloride-treated hearts compared with 2.3 +/- 0.9-mu-M in nontreated hearts. After 20 minutes of ischemia, Na(i) in the untreated heart was threefold greater than control, whereas in the amiloride-treated heart, Na(i) was not significantly different from control. These data are consistent with the involvement of Na-Ca exchange in the rise in Ca(i) during ischemia. In addition, recovery of contractile function during reperfusion after 20 minutes of ischemia was significantly better in amiloride-treated hearts (71 +/- 10%) than in nontreated hearts (24 +/- 13%). These data are consistent with the hypothesis suggesting that the elevation in Ca(i) during ischemia may contribute to postischemic contractile dysfunction. C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. RP MURPHY, E (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. FU NHLBI NIH HHS [HL-39752, R01 HL039752] NR 43 TC 303 Z9 308 U1 0 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY PY 1991 VL 68 IS 5 BP 1250 EP 1258 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA FK505 UT WOS:A1991FK50500007 PM 1902148 ER PT J AU METZGER, H AF METZGER, H TI THE HIGH-AFFINITY RECEPTOR FOR IGE ON MAST-CELLS SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Review ID BASOPHILIC LEUKEMIA-CELLS; PROTEIN KINASE-C; HUMAN IMMUNOGLOBULIN-E; FC-EPSILON-RI; HISTAMINE-RELEASE; CROSS-LINKING; TRANSFECTED CELLS; DE-GRANULATION; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION RP METZGER, H (reprint author), NIAMSD,CHEM IMMUNOL SECT,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892, USA. NR 88 TC 74 Z9 76 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD MAY PY 1991 VL 21 IS 3 BP 269 EP 279 DI 10.1111/j.1365-2222.1991.tb01658.x PG 11 WC Allergy; Immunology SC Allergy; Immunology GA FM938 UT WOS:A1991FM93800003 PM 1830826 ER PT J AU CHAN, CC ROBERGE, FG NI, M ZHANG, W NUSSENBLATT, RB AF CHAN, CC ROBERGE, FG NI, M ZHANG, W NUSSENBLATT, RB TI INJURY OF MULLER CELLS INCREASES THE INCIDENCE OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID ALPHA-AMINOADIPIC ACID; T-HELPER LYMPHOCYTES; ENDOTHELIAL-CELLS; S-ANTIGEN; PROTEIN; LINES; RAT; EAU C1 NEI,PATHOL LAB,BETHESDA,MD 20892. RP CHAN, CC (reprint author), NEI,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 20 TC 12 Z9 13 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 MAY PY 1991 VL 59 IS 2 BP 201 EP 207 DI 10.1016/0090-1229(91)90018-6 PG 7 WC Immunology; Pathology SC Immunology; Pathology GA FG162 UT WOS:A1991FG16200003 PM 2009640 ER PT J AU DRELL, W SKODA, J WELCH, AD AF DRELL, W SKODA, J WELCH, AD TI THE CHEMOTHERAPY OF PSORIASIS WITH AZARIBINE - MIRAGE OR MIRACLE SO COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS LA English DT Article ID 6-AZAURIDINE TRIACETATE; HOMOCYSTINEMIA; SERUM; THROMBOSIS; RELEVANCE; DECREASE AB An antimetabolite, administered orally, which alleviates the symptoms and signs of severe psoriasis, azaribine (triacetyl-6-azauridine), was approved by the Food and Drug Administration (FDA of the USA) for clinical use in 1975, but 18 months later approval was withdrawn. The mechanism of action of azaribine (as a precursor of 6-azauridine 5'-monophosphate) is described and the probable cause of the infrequent vascular thromboses and a means of preventing them (by the co-administration of pyridoxine) are discussed. C1 CZECHOSLOVAK ACAD SCI,INST ORGAN CHEM & BIOCHEM,CS-11142 PRAGUE 1,CZECH REPUBLIC. NCI,BETHESDA,MD 20205. RP DRELL, W (reprint author), UR LABS INC,SAN DIEGO,CA 92037, USA. NR 65 TC 3 Z9 3 U1 1 U2 1 PU INST ORGANIC CHEM AND BIOCHEM PI PRAGUE 6 PA ACAD OF SCI CZECH REPUBLIC FLEMINGOVO NAM 2, PRAGUE 6, CZECH REPUBLIC 166 10 SN 0010-0765 J9 COLLECT CZECH CHEM C JI Collect. Czech. Chem. Commun. PD MAY PY 1991 VL 56 IS 5 BP 945 EP 953 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA FP995 UT WOS:A1991FP99500001 ER PT J AU IHDE, DC MINNA, JD AF IHDE, DC MINNA, JD TI NON-SMALL-CELL LUNG-CANCER .2. TREATMENT SO CURRENT PROBLEMS IN CANCER LA English DT Review ID THERAPY ONCOLOGY GROUP; PROSPECTIVE RANDOMIZED TRIAL; HIGH-DOSE CISPLATIN; FACTORS AFFECTING SURVIVAL; SINGLE-AGENT CHEMOTHERAPY; VINDESINE PLUS CISPLATIN; SUPERIOR SULCUS TUMORS; RADIATION-THERAPY; COMBINATION CHEMOTHERAPY; STAGE-III AB Squamous, large cell, and adenocarcinoma, collectively termed non-small cell lung cancer (NSCLC), are diagnosed in approximately 75% of patients with lung cancer in the United States. The treatment of these three tumor cell types is approached in virtually identical fashion because, in contrast to small cell carcinoma of the lung, NSCLC more frequently presents with localized disease at the time of diagnosis and is thus more often amenable to surgical resection but less frequently responds to chemotherapy and irradiation. Cigarette smoking is etiologically related to the development of NSCLC in the great majority of cases. Genetic mutations in dominant oncogenes such as K-ras, loss of genetic material on chromosomes 3p, 11p, and 17p, and deletions or mutations in tumor suppressor genes such as rb and p53 have been documented in NSCLC tumors and tumor cell lines. NSCLC is diagnosed because of symptoms related to the primary tumor or regional or distant metastases, as an incidental finding on chest radiograph, or rarely because of a paraneoplastic syndrome such as hypercalcemia or hypertrophic pulmonary osteoarthropathy. Screening smokers with periodic chest radiographs and sputum cytologic examination has not been shown to reduce mortality. The diagnosis of NSCLC is usually established by fiberoptic bronchoscopy or percutaneous fine-needle aspiration, by biopsy of a regional or distant metastic site, or at the time of thoracotomy. Pathologically, NSCLC arises in a setting of bronchial mucosal metaplasia and dysplasia that progressively increase over time. Squamous carcinoma more often presents as a central endobronchial lesion, while large cell and adenocarcinoma have a tendency to arise in the lung periphery and invade the pleura. Once the diagnosis is made, the extent of tumor dissemination is determined. Since most NSCLC patients who survive 5 years or longer have undergone surgical resection of their cancers, the focus of the staging process is to determine whether the patient is a candidate for thoracotomy with curative intent. The dominant prognostic factors in NSCLC are extent of tumor dissemination, ambulatory or performance status, and degree of weight loss. Stages I and II NSCLC, which are confined within the pleural reflection, are managed by surgical resection whenever possible, with approximate 5-year survival of 45% and 25%, respectively. Patients with stage IIIa cancers, in which the primary tumor has extended through the pleura or metastasized to ipsilateral or subcarinal lymph nodes, can occassionally be surgically resected but are often managed with definitive thoracic irradiation and have 5-year survival of approximately 15%. In completely surgically resected NSCLC, postoperative irradiation reduces the local recurrence rate but has not been shown to improve survival. Stage IIIb cancer, which is more advanced than stage IIIa but without distant metastases, is frequently treated with chest irradiation; 5-year survival is less than 5%. Thoracic radiotherapy can cure a small fraction of stage III NSCLC patients and perhaps up to 15% to 20% of stages I and II patients with medical contraindications to surgery. Although higher doses of irradiation up to 6,000 cGy with conventional fractionation are associated with improved response rates and better local control, survival is not improved, almost certainly because of the predominant effects of distant metatases in determining eventual outcome. Patients with stage IV NSCLC, in which distant metastases are present at diagnosis, have only anecdotal 5-year survival. In the past decade, however, some evidence of biologic effects of cisplatin-based combination chemotherapy has been documented. Although chemotherapy cannot be said to unequivocally improve survival in any stage of NSCLC, some prospective randomized trials have shown survival or disease-free survival advantages in patients with overt stage IV disease or as an adjuvant treatment before or after definitive irradiation or surgery. Other such trials have been negative, however, and continued clinical trials will be required before a role for chemotherapy in NSCLC can be considered to be established. At present, outside the setting of a clinical trial, patients should receive chemotherapy only if they are categorically incurable by surgery or irradiation, have no significant symptoms that could be readily palliated with irradiation, are fully ambulatory, have assessable tumor lesions so that treatment can be discontinued if ineffective, and desire therapy after being informed of its limitations. C1 NATL NAVAL MED CTR, NATL CANC INST, NAVY MED ONCOL BRANCH, BETHESDA, MD 20814 USA. RP IHDE, DC (reprint author), UNIFORMED SERV UNIV HLTH SCI, MED, BETHESDA, MD 20814 USA. NR 176 TC 19 Z9 19 U1 1 U2 7 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0147-0272 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD MAY-JUN PY 1991 VL 15 IS 3 BP 109 EP 154 DI 10.1016/0147-0272(91)90012-Y PG 46 WC Oncology SC Oncology GA FR022 UT WOS:A1991FR02200001 ER PT J AU KUNIMOTO, DY ALLISON, KC WATSON, C FUERST, T ARMSTRONG, GD PAUL, W STROBER, W AF KUNIMOTO, DY ALLISON, KC WATSON, C FUERST, T ARMSTRONG, GD PAUL, W STROBER, W TI HIGH-LEVEL PRODUCTION OF MURINE INTERLEUKIN-5 (IL-5) UTILIZING RECOMBINANT BACULOVIRUS EXPRESSION - PURIFICATION OF THE RIL-5 AND ITS USE IN ASSESSING THE BIOLOGIC ROLE OF IL-5 GLYCOSYLATION SO CYTOKINE LA English DT Article DE IL-5; BACULOVIRUS; RECOMBINANT; MURINE; GLYCOSYLATION ID ENHANCES IGA PRODUCTION; B-CELL DIFFERENTIATION; REPLACING FACTOR TRF; TOXIC LYMPHOCYTES-T; INSECT CELLS; PHYSICOCHEMICAL CHARACTERIZATION; SECRETION; VECTOR; MOUSE; RECEPTOR C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. UNIV ALBERTA,DEPT MED,EDMONTON T6G 2E1,ALBERTA,CANADA. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NIAID,BIOCHEM LAB,BETHESDA,MD 20892. NR 34 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAY PY 1991 VL 3 IS 3 BP 224 EP 230 DI 10.1016/1043-4666(91)90020-E PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA FZ155 UT WOS:A1991FZ15500008 PM 1883961 ER PT J AU FEUILLARD, J GOUY, H BISMUTH, G LEE, LM DEBRE, P KORNER, M AF FEUILLARD, J GOUY, H BISMUTH, G LEE, LM DEBRE, P KORNER, M TI NF-KAPPA-B ACTIVATION BY TUMOR-NECROSIS-FACTOR-ALPHA IN THE JURKAT T-CELL LINE IS INDEPENDENT OF PROTEIN KINASE-A, PROTEIN-KINASE-C, AND CA2+-REGULATED KINASES SO CYTOKINE LA English DT Article DE NF-KAPPA-B; PROTEIN KINASES; T-CELLS; TNF-ALPHA ID HUMAN-IMMUNODEFICIENCY-VIRUS; FACTOR SIGNAL TRANSDUCTION; ENHANCER-BINDING-PROTEIN; TRANSCRIPTION FACTOR; MOLECULAR-CLONING; EXPRESSION; RECEPTOR; DNA; TRANSLOCATION; SEQUENCES C1 HOP LA PITIE SALPETRIERE,IMMUNOL CELLULAIRE & TISSULAIRE LAB,CNRS,U625,F-75013 PARIS,FRANCE. NCI,FREDERICK CANC RES FACIL,NUCL ACID & PROT SYNTH LAB,FREDERICK,MD 21701. NR 45 TC 66 Z9 66 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAY PY 1991 VL 3 IS 3 BP 257 EP 265 DI 10.1016/1043-4666(91)90025-9 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA FZ155 UT WOS:A1991FZ15500013 PM 1653056 ER PT J AU FLUCHER, BE TERASAKI, M CHIN, H BEELER, TJ DANIELS, MP AF FLUCHER, BE TERASAKI, M CHIN, H BEELER, TJ DANIELS, MP TI BIOGENESIS OF TRANSVERSE TUBULES IN SKELETAL-MUSCLE INVITRO SO DEVELOPMENTAL BIOLOGY LA English DT Article ID ACETYLCHOLINE-RECEPTOR; CALCIUM CHANNELS; MEMBRANES; LOCALIZATION; JUNCTIONS; PROTEINS; CULTURES; SUBUNIT; SURFACE; CA-2+ C1 NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT BIOCHEM,BETHESDA,MD 20814. RP FLUCHER, BE (reprint author), NINCDS,NEUROBIOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 48 Z9 49 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY PY 1991 VL 145 IS 1 BP 77 EP 90 DI 10.1016/0012-1606(91)90214-N PG 14 WC Developmental Biology SC Developmental Biology GA FH617 UT WOS:A1991FH61700007 PM 2019326 ER PT J AU IMANO, E KADOWAKI, H KADOWAKI, T IWAMA, N WATARAI, T KAWAMORI, R KAMADA, T TAYLOR, SI AF IMANO, E KADOWAKI, H KADOWAKI, T IWAMA, N WATARAI, T KAWAMORI, R KAMADA, T TAYLOR, SI TI 2 PATIENTS WITH INSULIN RESISTANCE DUE TO DECREASED LEVELS OF INSULIN-RECEPTOR MESSENGER-RNA SO DIABETES LA English DT Article ID POLYMERASE CHAIN-REACTION; TYROSINE KINASE DOMAIN; PROMOTER REGION; ACANTHOSIS NIGRICANS; IMPAIRS TRANSPORT; GENE-EXPRESSION; MUTANT ALLELES; POINT MUTATION; SEQUENCE; BINDING AB Mutations have been identified in the insulin-receptor gene in insulin-resistant patients. We studied two patients with acanthosis nigricans and insulin resistance caused by a decrease in the number of cell surface insulin receptors. Patient 1 was an 11-yr-old boy with a fasting insulin level of 2130 pM; patient 2 was a 14-yr-old girl with hyperandrogenism and a fasting insulin level of 580-740 pM. Based on Southern-blotting studies, the structure of both alleles of the insulin-receptor gene in both patients appeared to be grossly normal. There was no evidence of insertions, deletions, or major rearrangements. Moreover, the nucleotide sequences of all 22 exons of the gene were normal in both patients. Thus, the predicted amino acid sequences of both patients' insulin receptors were normal. In Epstein-Barr virus-transformed lymphoblasts from patient 1, insulin-receptor mRNA levels were so low they could not be detected with an RNase A protection assay, whereas mRNA levels from patient 2 were in the lower half of the normal range. By use of a more sensitive assay based on the polymerase chain reaction, insulin-receptor mRNA could be detected in Epstein-Barr virus-transformed lymphoblasts from both patients. Moreover, because of the existence of silent polymorphisms in the nucleotide sequences, it was possible to differentiate the two alleles of the insulin-receptor gene in both patients. In patient 2, the two alleles were expressed asymmetrically, with 90% of the mRNA molecules having been transcribed from one allele but only 10% transcribed from the second allele. This suggests that there is an unidentified mutation in the underexpressed allele that acts in a cis-dominant fashion to decrease insulin-receptor mRNA levels. However, in patient 1, both alleles were expressed symmetrically in similarly low levels. Although not proven, it seems likely that the mutations that decrease insulin-receptor mRNA levels in patient 1 also map to the insulin-receptor locus. C1 NIDDKD,DIABET BRANCH,BLDG 10,ROOM 8S-243,BETHESDA,MD 20892. OSAKA UNIV,SCH MED,DEPT MED 1,OSAKA,JAPAN. NR 38 TC 37 Z9 38 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1991 VL 40 IS 5 BP 548 EP 557 DI 10.2337/diabetes.40.5.548 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FL179 UT WOS:A1991FL17900005 PM 1673662 ER PT J AU HARRIS, MI AF HARRIS, MI TI HYPERCHOLESTEROLEMIA IN DIABETES AND GLUCOSE-INTOLERANCE IN THE UNITED-STATES POPULATION SO DIABETES CARE LA English DT Article ID CORONARY HEART-DISEASE; RISK-FACTORS; CHOLESTEROL LEVELS; FOLLOW-UP; LIPOPROTEIN CHOLESTEROL; MYOCARDIAL-INFARCTION; PLASMA-LIPIDS; MORTALITY; TOLERANCE; MELLITUS AB The prevalence of hypercholesterolemia, according to the guidelines of the National Cholesterol Education Program, has been determined in a national survey of diabetes and glucose intolerance. Rates of elevated total cholesterol in people with diabetes in the United States are only slightly greater than in those without diabetes after adjusting for age and sex. Nevertheless, high or borderline high total cholesterol is common in diabetes and is present in 70% of adults with diagnosed diabetes and 77% with undiagnosed diabetes in the U.S. population. Of these individuals, 95% have evidence of coronary heart disease or two or more risk factors for heart disease and should therefore have their low-density lipoprotein (LDL) cholesterol measured. Based on our national data, LDL cholesterol levels warranting dietary treatment for hypercholesterolemia would be expected in 85% of these people. Although elevated LDL cholesterol is uncommon in people with diabetes who have total cholesterol of < 200 mg/dl, other risk factors for coronary heart disease are very frequent (100% of men, 73% of women), and low total and LDL cholesterol may mask low high-density lipoprotein cholesterol. Therefore, investigation of blood lipid levels and coronary heart disease risk factors should be routing in all patients with diabetes, and treatment strategies should include management of lipid disorders and the multiple other risk factors for coronary heart disease that are highly prevalent in these patients. RP HARRIS, MI (reprint author), NIDDK,WESTWOOD BLDG,ROOM 620,BETHESDA,MD 20892, USA. NR 50 TC 60 Z9 61 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 MAY PY 1991 VL 14 IS 5 BP 366 EP 374 DI 10.2337/diacare.14.5.366 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FJ605 UT WOS:A1991FJ60500003 PM 2060448 ER PT J AU CETNAROWSKICROPP, AB AF CETNAROWSKICROPP, AB TI QUINAPRIL - A NEW 2ND-GENERATION ACE INHIBITOR SO DICP-THE ANNALS OF PHARMACOTHERAPY LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; CHRONIC HEART-FAILURE; HEALTHY-VOLUNTEERS; ACTIVE METABOLITE; CONTROLLED TRIAL; CARDIAC-FAILURE; NON-SULFHYDRYL; DOUBLE-BLIND; PHARMACOKINETICS; CAPTOPRIL AB Quinapril is a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor. The drug undergoes hepatic hydrolysis into its major active diacid metabolite, quinaprilat, and two minor inactive metabolites. On a weight basis quinaprilat is three times as potent an ACE inhibitor as quinapril. Approximately 60 percent of an oral dose of quinapril is absorbed. In contrast with captopril, the absorption of quinapril is unaffected by food. Peak serum concentrations of quinapril and quinapril are achieved within one and two hours, respectively. Approximately 61 percent of an orally administered dose is excreted in the urine, principally as quinaprilat. The elimination half-life of quinaprilat is three hours, but is prolonged up to 11 hours in patients with renal dysfunction. Quinapril dose reduction is recommended in patients with a creatinine clearance of 0.50 mL/sec or less. In the elderly the elimination of quinaprilat is reduced and correlates well with renal function. In patients with cirrhosis the hydrolysis of quinapril to quinaprilat is impaired resulting in lower plasma quinaprilat concentrations and up to a two-fold increase in quinapril half-life. Quinaprilat has a strong binding capacity to tissue ACE allowing for once-daily dosing. The recommended starting dose for quinapril is 20 mg/d. The nature and incidence of adverse reactions to quinapril are similar to those of enalapril and captopril. Quinapril's antihypertensive efficacy is equal to that of captopril and enalapril. A small number of patients with congestive heart failure (CHF) have been treated with quinapril. Preliminary data indicate that quinapril is an equally effective therapeutic alternative to presently available ACE inhibitors in the treatment of CHF. Quinapril, a second-generation ACE inhibitor, has not been shown to offer significant clinical advantage over enalapril. In formulary evaluations quinapril may be considered therapeutically equivalent to enalapril. RP CETNAROWSKICROPP, AB (reprint author), NHLBI,WARREN GRANT MAGNESON CLIN CTR,CARDIOL BRANCH,BETHESDA,MD 20892, USA. NR 48 TC 7 Z9 8 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 0012-6578 J9 DICP ANN PHARMAC PD MAY PY 1991 VL 25 IS 5 BP 499 EP 504 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FL571 UT WOS:A1991FL57100012 PM 2068835 ER PT J AU VALDEZ, IH FOX, PC AF VALDEZ, IH FOX, PC TI INTERACTIONS OF THE SALIVARY AND GASTROINTESTINAL SYSTEMS .1. THE ROLE OF SALIVA IN DIGESTION SO DIGESTIVE DISEASES LA English DT Article RP VALDEZ, IH (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1N-113,BETHESDA,MD 20892, USA. NR 0 TC 25 Z9 25 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PD MAY-JUN PY 1991 VL 9 IS 3 BP 125 EP 132 DI 10.1159/000171298 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA FT219 UT WOS:A1991FT21900001 PM 1714362 ER PT J AU BLANEY, SM BALIS, FM POPLACK, DG AF BLANEY, SM BALIS, FM POPLACK, DG TI CURRENT PHARMACOLOGICAL TREATMENT APPROACHES TO CENTRAL-NERVOUS-SYSTEM LEUKEMIA SO DRUGS LA English DT Article ID DOSE CYTOSINE-ARABINOSIDE; ACUTE LYMPHOBLASTIC-LEUKEMIA; CANCER-STUDY-GROUP; CEREBROSPINAL-FLUID; MENINGEAL LEUKEMIA; INTRAVENOUS METHOTREXATE; INTRATHECAL METHOTREXATE; CLINICAL PHARMACOLOGY; LYMPHOCYTIC-LEUKEMIA; CHILDHOOD LEUKEMIA AB Significant advances in the treatment and prevention of meningeal leukaemia have been made in the past 3 decades. This progress has resulted from the development of innovative approaches to treatment as well as a better understanding of the pharmacokinetics and pharmacodynamics of the commonly used antileukaemic agents. Intrathecal therapy, via the intralumbar or intraventricular route, is a form of regional therapy that results in the delivery of very high drug concentrations to the principal target tumour site (the meninges) using a relatively small drug dose, thereby minimising both systemic drug exposure and systemic toxicity. The dosage and schedules, clinical pharmacology and toxicities of the commonly used intrathecal agents, methotrexate and cytarabine (cytosine arabinoside; Ara-C) are discussed in detail. Another approach which has been used to overcome the poor penetration of antileukaemic drugs into the CNS has been the use of high-dose systemic therapy. This strategy has been successfully applied in the treatment of meningeal leukaemia using both high-dose methotrexate and high-dose cytarabine. The clinical pharmacology, toxicities, and potential limitations of this approach are outlined. Finally, new agents that are currently undergoing clinical evaluation and future directions for research are also discussed. C1 NCI,PEDIAT BRANCH,LEUKEMIA BIOL SECT,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NR 64 TC 26 Z9 27 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PD MAY PY 1991 VL 41 IS 5 BP 702 EP 716 DI 10.2165/00003495-199141050-00003 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA FP408 UT WOS:A1991FP40800003 PM 1712705 ER PT J AU POSPICHAL, J TIETZ, D ITTVERAH, TR HALPERN, D CHRAMBACH, A AF POSPICHAL, J TIETZ, D ITTVERAH, TR HALPERN, D CHRAMBACH, A TI GEL-ELECTROPHORESIS OF POLYSTYRENE PARTICLES IN GLUTARALDEHYDE CROSS-LINKED POLYVINYL-ALCOHOL SO ELECTROPHORESIS LA English DT Article ID SIZE STANDARDS; FERGUSON PLOTS; AGAROSE; POLYACRYLAMIDE AB Polystyrene sulfate and carboxylate particles (19-189 nm radius) were subjected to electrophoresis in glutaraldehyde crosslinked polyvinyl alcohol of molecular weight 25.000 and 650.000 Da at various concentrations. The degree of crosslinking is severely limited by the mechanical properties of the gels that deteriorate beyond a glutaraldehyde concentration which decreases with increasing polyvinyl alcohol chain length. The effective fiber radius of the short-chain and long-chain polymer fiber was 45 +/- 25 and 131 +/- 47 nm, respectively. Thus, these media do not significantly exceed the apparent fiber thickness of agarose are more difficult to prepare-but are well-defined synthetic products rather than natural ones, and have the advantage of carrying no net charge and can therefore be expected to exhibit no electroendosmosis. C1 NICHHD,THEORET & PHYS BIOL,MACROMOLEC ANAL SECT,BLDG 10,RM 6C101,BETHESDA,MD 20892. POLYSCI INC,WARRINGTON,PA. NR 21 TC 6 Z9 6 U1 0 U2 2 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 MAY PY 1991 VL 12 IS 5 BP 338 EP 341 DI 10.1002/elps.1150120504 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA FU276 UT WOS:A1991FU27600003 PM 1935874 ER PT J AU RANCE, NE YOUNG, WS AF RANCE, NE YOUNG, WS TI HYPERTROPHY AND INCREASED GENE-EXPRESSION OF NEURONS CONTAINING NEUROKININ-B AND SUBSTANCE-P MESSENGER RIBONUCLEIC-ACIDS IN THE HYPOTHALAMI OF POSTMENOPAUSAL WOMEN SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE SECRETION; MEDIAL BASAL HYPOTHALAMUS; IMMUNOREACTIVE NEURONS; SEQUENCE-ANALYSIS; CARCINOID FLUSH; CIRCULATING TACHYKININS; MENOPAUSAL FLUSHES; FACTOR PRECURSOR; FEMALE RAT; CDNA AB We have previously described hypertrophy of neurons containing estrogen receptor mRNA in the infundibular nucleus of postmenopausal women. In the present investigation we identified peptide mRNAs in the hypertrophied neurons and determined whether postmenopausal neuronal hypertrophy was accompanied by changes in gene expression. In the first study in situ hybridization was performed on sections from hypothalami of postmenopausal women (n = 3) using synthetic S-35-labeled cDNA probes complementary to mRNAs encoding estrogen receptor, substance-P (SP), neurokinin-B (NKB), POMC, cholecystokinin, dynorphin, CRF, enkephalin, galanin, neuropeptide-Y, GH-releasing hormone, and tyrosine hydroxylase. Neuronal cross-sectional areas and cell densities were measured with the aid of a computer microscope system. Neurons labeled with the NKB and SP probes were comparable in size, morphology, and distribution to the hypertrophied neurons containing estrogen receptor mRNA. In contrast, neurons labeled with other cDNA probes were sparsely distributed (CRF and dynorphin), smaller in size (neuropeptide-Y, galanin, GH-releasing hormone, enkephalin, cholecystokinin, and POMC), or located anterior to the hypertrophied population (tyrosine hydroxylase). In the second study sections from hypothalami of premenopausal (n = 3) and postmenopausal (n = 3) women were incubated with cDNA probes complementary to SP or NKB mRNAs. The mean cross-sectional areas of postmenopausal infundibular neurons containing NKB and SP mRNAs increased to 194% and 176% of premenopausal values, respectively. The autoradiographic grain densities of infundibular neurons labeled with either probe were also significantly increased in the postmenopausal group. Finally, the numbers of labeled neurons/tissue increased 6-fold (SP) and 15-fold (NKB) in the postmenopausal infundibular nucleus. These data demonstrate that human menopause is associated with marked increases in hypothalamic NKB and SP gene expression. We propose that neurons containing estrogen receptor, SP, and NKB mRNAs participate in the hypothalamic circuitry regulating estrogen negative feedback in the human. C1 UNIV ARIZONA,COLL MED,DEPT NEUROL,TUCSON,AZ 85724. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP RANCE, NE (reprint author), UNIV ARIZONA,DEPT PATHOL,1501 N CAMPBELL,TUCSON,AZ 85724, USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NCRR NIH HHS [2S07-RR-05675-22]; NIA NIH HHS [AG-O9214] NR 54 TC 125 Z9 129 U1 0 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1991 VL 128 IS 5 BP 2239 EP 2247 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FJ396 UT WOS:A1991FJ39600006 PM 1708331 ER PT J AU MASTERS, BA WERNER, H ROBERTS, CT LEROITH, D RAIZADA, MK AF MASTERS, BA WERNER, H ROBERTS, CT LEROITH, D RAIZADA, MK TI DEVELOPMENTAL REGULATION OF INSULIN-LIKE GROWTH FACTOR-I-STIMULATED GLUCOSE TRANSPORTER IN RAT-BRAIN ASTROCYTES SO ENDOCRINOLOGY LA English DT Article ID FACTOR BINDING-PROTEINS; GLIAL-CELLS; PRIMARY CULTURES; SOMATOMEDIN-C; DNA-SYNTHESIS; EXPRESSION; ACETYLCHOLINE; RECEPTORS; FETAL AB Astrocytic glial cells from 1- and 21-day-old rat brains were established in primary culture to study the expression of insulin-like growth factor-I (IGF-I) receptors and IGF-I-stimulated glucose transporter (Glut-1). Astrocytes from both age groups expressed specific high affinity IGF-I receptors, whose relative affinities for IGF-I, IGF-II, and insulin were comparable. However, the total number of binding sites and IGF-I receptor mRNA levels were 148% and 240% higher in astrocytes from 21-day-old compared with 1-day-old brains. IGF-I caused a dose-dependent stimulation of [H-3]2-deoxy-D-glucose ([H-3]dGlc) uptake in astrocytes from 1-day-old brains. This was associated with increases in Glut-1 protein and mRNA levels. In contrast, astrocytes from 21-day-old brains exhibited a 58% decrease in the binding capacity and a 77% decrease in the steady state levels of Glut-1 protein and its mRNA. In addition, IGF-I failed to stimulate the Glut-1 system in these cells. This lack of IGF-I effect is not due to an alteration inherent to the Glut-1 system, since 12-O-tetradecanoyl-phorbol-13-acetate stimulated [H-3]dGlc uptake and Glut-1 protein and its mRNA levels. These observations suggest that changes in basal and IGF-I-stimulated Glut-1 system in brain astrocytes may be developmentally regulated. C1 NIDDKD,DIABETES BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BETHESDA,MD 20892. UNIV FLORIDA,COLL MED,DEPT PHYSIOL,GAINESVILLE,FL 32610. OI Roberts, Charles/0000-0003-1756-5772 NR 34 TC 31 Z9 31 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 MAY PY 1991 VL 128 IS 5 BP 2548 EP 2557 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FJ396 UT WOS:A1991FJ39600045 PM 1850355 ER PT J AU KAMILARIS, TC DEBOLD, CR JOHNSON, EO MAMALAKI, E LISTWAK, SJ CALOGERO, AE KALOGERAS, KT GOLD, PW ORTH, DN AF KAMILARIS, TC DEBOLD, CR JOHNSON, EO MAMALAKI, E LISTWAK, SJ CALOGERO, AE KALOGERAS, KT GOLD, PW ORTH, DN TI EFFECTS OF SHORT AND LONG DURATION HYPOTHYROIDISM AND HYPERTHYROIDISM ON THE PLASMA ADRENOCORTICOTROPIN AND CORTICOSTERONE RESPONSES TO OVINE CORTICOTROPIN-RELEASING HORMONE IN RATS SO ENDOCRINOLOGY LA English DT Article ID PITUITARY-ADRENAL FUNCTION; CUSHINGS-DISEASE; STIMULATION TEST; THYROXINE; DEPRESSION; SECRETION; ACTH; AID AB We report here a study of the plasma ACTH and corticosterone response to synthetic ovine CRH (oCRH) in hypothyroid and hyperthyroid rats studied 7, 15, and 60 days after either thyroidectomy or the administration of pharmacological doses of T4. The purpose of this study was to further clarify the time-dependent effects of alterations in thyroid status on the functional integrity of the hypothalamic-pituitary-adrenal axis and to aid in the interpretation of the oCRH stimulation test in hypo- and hyperthyroid states. Our data demonstrate that hypothyroid rats have a significant reduction in the cerebrospinal fluid (CSF) levels of corticosterone and a significant decrease in adrenal weight in association with signifiant increases in the plasma ACTH response to oCRH. On the other hand, the corticosterone response to the ACTH released during the oCRH stimulation test significantly reduced in hypothyroidism. With increasing duration of thyroidectomy-induced hypothyroidism, there was a progressive fall in CSF corticosterone levels, a progressive increase in the plasma ACTH response to oCRH, and a gradual normalization of the corticosterone responses to the ACTH released during oCRH stimulation. Our findings in hyperthyroid rats were generally the converse of those seen in hypothyroidism. Hence, there was a significant increase in the CSF levels of corticosterone and a significant increase in adrenal weight in association with an initial slight decrease in the ACTH response to oCRH. On the other hand, the corticosterone response to the ACTH released during oCRH stimulation was significantly increased. There was a gradual increase in the magnitude of the rise in CSF corticosterone levels with time, as well as a gradual normalization of adrenocortical responses during oCRH stimulation. The ACTH plasma clearance rates were similar in hypo-, hyper-, and euthyroid rats. Our data do not permit definitive identification of the precise locus in the hypothalamic-pituitary-adrenal axis that is principally affected by experimentally induced alterations in thyroid status. However, these data are most compatible with a subtle hypothyroid-induced centrally mediated adrenal insufficiency and a subtle hyperthyroid-induced centrally mediated hypercortisolism. These data also suggest that alterations in hypothalamic-pituitary-adrenal function in states of disturbed thyroid function become somewhat more pronounced as the duration of thyroid dysfunction increases. The fact that pituitary-adrenal responses to oCRH are consistently altered in states of thyroid dysfunction may be relevant to the clinical interpretation of oCRH stimulation tests. This is especially so because this test is commonly employed in clinical populations that show significant disturbances in thyroid function, including patients with major depression, Cushing's disease, and anorexia nervosa. C1 PARK NICOLLET MED CTR,DIV ENDOCRINOL,MINNEAPOLIS,MN 55416. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MOLEC PHYSIOL & BIOPHYS,NASHVILLE,TN 37232. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP KAMILARIS, TC (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. FU PHS HHS [5-RO1-33334] NR 36 TC 62 Z9 66 U1 0 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1991 VL 128 IS 5 BP 2567 EP 2576 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FJ396 UT WOS:A1991FJ39600047 PM 1850357 ER PT J AU LIN, KH WILLINGHAM, MC LIANG, CM CHENG, SY AF LIN, KH WILLINGHAM, MC LIANG, CM CHENG, SY TI INTRACELLULAR-DISTRIBUTION OF THE ENDOGENOUS AND TRANSFECTED-BETA-FORM OF THYROID-HORMONE NUCLEAR RECEPTOR VISUALIZED BY THE USE OF DOMAIN-SPECIFIC MONOCLONAL-ANTIBODIES SO ENDOCRINOLOGY LA English DT Article ID C-ERBA; BINDING-PROTEIN; CDNA CLONE; EXPRESSION; CELLS; IDENTIFICATION; TISSUES; SYSTEM AB To study the regulation, tissue distribution, and subcellular localization of nuclear receptor for thyroid hormone, monoclonal antibodies (mAbs) against the human placental cerbA (hTR-beta-1) protein were prepared. hTR-beta-1 was expressed in Escherichia coli and purified to apparent homogeneity. The purified hTR-beta-1 was used to produce monoclonal antibodies. Three hybridomas, secreting mAb J51, J52, and J53, were isolated. All of these mAbs recognized hTR-beta-1. J51 and J52 belong to the immunoglobulin G1-k subclass; J53 is an IgM. To evaluate cross-reactivity with other classes of c-erbAs, the three mAbs were used to immunoprecipitate the in vitro translation products of human (h) TR-alpha-1, TR-alpha-2, rat (r) TR-beta-1, TR-alpha-1, and TR-alpha-2. None of these three mAbs reacted with h- or rTR-alpha-1 and TR-alpha-2. J51 did not react with rTR-beta-1, but J52 and J53 cross-reacted with rTR-beta-1 with the same activity as hTR-beta-1. To localize the epitopes in the hTR-beta-1 molecule, [S-35]methionine-labeled and truncated hTR-beta-1 containing the hormone-binding domain E (Lys235-Asp456; Lys201-Pro414), domain D (Met169-Asp456), or the DNA-binding domain C (Glu100-Asp456) were expressed in E. coli and purified. Immunoprecipitation of the above truncated hTR-beta-1 with mAbs indicated that the epitopes for J51 and J52 were located in two different sites in the A/B domain. The epitope for J53 was located in the E domain. Using immunocytochemistry and mAb J52, the endogenous TR-beta-1 in rat pituitary GH3 cells was visualized to be exclusively present in nuclei. The transfected hTR-beta-1 in monkey COS-1 and human choriocarcinoma JEG-3 cells was recognized by both J51 and J52. Interestingly, the intracellular localization of the transfected hTR-beta-1 or rTR-beta-1 in the above two cell lines depended on the level of expression. TR-beta-1 expressed at low levels was found exclusively in nuclei. However, for high level expression of TR-beta-1, cytoplasmic localization was also detected. J53, however, failed to detect nuclear fluorescence of the endogenous and transfected TR-beta-1 in fixed cells, suggesting that its antigenic site might be occluded. Localization of the endogenous and transfected TR-beta-1 in nuclei indicated that these two receptor proteins are structurally indistinguishable. Furthermore, the findings that TR-beta-1 could be localized in the cytoplasm when receptor was overexpressed suggested finite numbers of acceptor sites for TR-beta-1 in the nucleus. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BLDG 37,ROOM 4B09,BETHESDA,MD 20892. US FDA,DIV BLOOD & BLOOD PROD,BETHESDA,MD 20892. NR 33 TC 46 Z9 46 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 MAY PY 1991 VL 128 IS 5 BP 2601 EP 2609 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FJ396 UT WOS:A1991FJ39600051 PM 1708338 ER PT J AU TAKAO, T MITCHELL, WM DESOUZA, EB AF TAKAO, T MITCHELL, WM DESOUZA, EB TI INTERLEUKIN-1 RECEPTORS IN MOUSE KIDNEY - IDENTIFICATION, LOCALIZATION, AND MODULATION BY LIPOPOLYSACCHARIDE TREATMENT SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; TUMOR NECROSIS FACTOR; GENE-EXPRESSION; ACTH RELEASE; IL-1; MICE; CELL; STIMULATION; ACTIVATION; ENDOTOXIN AB The cytokine interleukin-1 (IL-1) has a variety of effects in the kidney involving induction of nephritis and renal injury. In addition, recent reports suggest that IL-1 regulates natriuresis and renin secretion in the kidney. To examine the potential sites of action of IL-1 in the kidney, we used iodine-125-labeled recombinant human interleukin-1-alpha ([I-125]IL-1-alpha) to identify and characterize IL-1 receptors in crude membrane preparations of mouse (C57BL/6) kidney. The binding of [I-125] IL-1-alpha was linear over a broad range of membrane protein concentrations, saturable, reversible, and of high affinity, with an equilibrium dissociation constant (K(d)) of 66 +/- 10 pM and a maximum number of binding sites of 1.04 +/- 0.24 fmol/mg protein. In competition studies, recombinant human IL-1-alpha, recombinant human IL-1-beta, and a weak IL-1-beta analog (IL-1-beta+) inhibited [I-125]IL-1-alpha binding to mouse kidney in parallel with their relative bioactivities in the T-cell comitogenesis assay, with inhibitory binding affinity constant (K(i)) values of 28 +/- 19, 53 +/- 23, and 5560 +/- 2098 pM, respectively; rat/human CRF and human tumor necrosis factor had no effect on [I-125]IL-1-alpha binding. In autoradiographic studies, IL-1 receptors were heterogeneously distributed in the kidney, with significantly higher densities present in the medulla than in the cortex. To study the effects of endogenous IL-1 in modulating [I-125]IL-1-alpha-binding sites in kidney, we injected 30-mu-g of the bacterial endotoxin lipopolysaccharide (LPS) to mice ip. Autoradiographic studies demonstrated substantial decreases in [I-125]IL-1-alpha binding in both the kidney cortex (control, 34.7 +/- 6.2 fmol/mg tissue equivalent; LPS, 11.3 +/- 0.3; P < 0.05) and medulla (52.7 +/- 8.1 vs. 26.0 +/- 1.0; P < 0.05) 24 h after injection of LPS. Saturation studies in whole kidney homogenates demonstrated that the LPS-induced decrease in [I-125]IL-1-alpha binding was primarily due to a down-regulation of IL-1 receptors (i.e. decrease in the maximum number of binding sites). The identification of IL-1 receptors in kidney with characteristics similar to those IL-1 receptors in the brain-endocrine-immune axis provides further support for a physiological role for IL-1 in regulating renal function. C1 NIDA,ADDICT RES CTR,NEUROBIOL LAB,BALTIMORE,MD 21224. NR 39 TC 19 Z9 19 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 MAY PY 1991 VL 128 IS 5 BP 2618 EP 2624 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FJ396 UT WOS:A1991FJ39600053 PM 1826879 ER PT J AU MULRONEY, SE HARAMATI, A ROBERTS, CT LEROITH, D AF MULRONEY, SE HARAMATI, A ROBERTS, CT LEROITH, D TI RENAL IGF-1 MESSENGER-RNA LEVELS ARE ENHANCED FOLLOWING UNILATERAL NEPHRECTOMY IN IMMATURE BUT NOT ADULT-RATS SO ENDOCRINOLOGY LA English DT Note ID GROWTH FACTOR-I; RIBONUCLEIC-ACID; HYPERTROPHY; EXPRESSION AB The increase in IGF-1 gene expression following unilateral nephrectomy (UNX) in adult rats is controversial. In this study we have examined whether developmental differences exist in the effect of UNX on IGF-1 gene expression. Immature (23 days) and adult (4 months) Wistar rats underwent a sham operation or left UNX, and were sacrificed 24 or 48 hrs later. IGF-1 mRNA levels were determined in left (control) and right (compensated) kidneys using solution hybridization/RNase protection assays. By 48 hrs post-UNX, remnant kidneys had grown 20 +/- 1% in adult rats (P < 0.05), and 69 +/- 5% in immature rats (P < 0.05). IGF-1 mRNA levels were not increased in the adult compensated kidneys at either 24 or 48 hrs post-UNX. In contrast, kidneys from immature rats 24 and 48 hrs post-UNX had an average 4-fold increase (P < 0.05) in exon 1 IGF-1 mRNA levels, and an average 3-fold increase (P < 0.05) in exon 2 mRNA levels. Thus, these findings suggest that there is an age-dependent difference in the effects of UNX on IGF-1 gene expression, and provide the first evidence that IGF-1 gene expression increases following unilateral nephrectomy immature rats. C1 NIDDK,DIABET BRANCH,CELLULAR & MOLEC PHYSIOL LAB,BETHESDA,MD. RP MULRONEY, SE (reprint author), GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20057, USA. NR 9 TC 40 Z9 40 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 MAY PY 1991 VL 128 IS 5 BP 2660 EP 2662 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FJ396 UT WOS:A1991FJ39600063 PM 2019274 ER PT J AU CUNNINGHAM, ET WADA, E CARTER, DB TRACEY, DE BATTEY, JF DESOUZA, EB AF CUNNINGHAM, ET WADA, E CARTER, DB TRACEY, DE BATTEY, JF DESOUZA, EB TI LOCALIZATION OF INTERLEUKIN-1 RECEPTOR MESSENGER-RNA IN MURINE HIPPOCAMPUS SO ENDOCRINOLOGY LA English DT Note ID BRAIN; RAT; SECRETION AB The cytokine interleukin-1 (IL-1) has numerous actions in brain, including pronounced neuroendocrine effects. Recent radioligand binding studies have identified high-affinity binding sites for I-125-recombinant human IL-1-alpha in the hippocampus with characteristics similar to those of IL-1 receptors in immune cells. The present study employed in situ hybridization histochemistry with S-35-labeled anti-sense cRNA probes derived from a full-length murine T-cell IL-1 receptor cDNA to identify cells producing IL-1 receptor mRNA in the murine hippocampus. An intense signal was observed over granule cells in the dentate gyrus. A weak to moderate signal was observed over the pyramidal cell layer of the hilus and CA3 region. Other aspects of the hippocampal formation, including the CA2 and CA1 regions, the subiculum, and the entorhinal area, displayed no signal above background. This distribution of IL-1 receptor mRNA was similar to that of I-125-IL-1-alpha binding sites and supports the growing body of evidence implicating IL-1 as a neurotransmitter/neuromodulator in brain. C1 UPJOHN CO,MOLEC BIOL RES,KALAMAZOO,MI 49007. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. UPJOHN CO,HYPERSENSIT DIS RES,KALAMAZOO,MI 49007. RP CUNNINGHAM, ET (reprint author), NIDA,ADDICT RES CTR,NEUROBIOL LAB,BALTIMORE,MD 21224, USA. NR 17 TC 66 Z9 66 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 MAY PY 1991 VL 128 IS 5 BP 2666 EP 2668 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FJ396 UT WOS:A1991FJ39600065 PM 1826880 ER PT J AU THEODORE, WH RAUBERTAS, RF PORTER, RJ NICE, F DEVINSKY, O REEVES, P BROMFIELD, E ITO, B BALISH, M AF THEODORE, WH RAUBERTAS, RF PORTER, RJ NICE, F DEVINSKY, O REEVES, P BROMFIELD, E ITO, B BALISH, M TI FELBAMATE - A CLINICAL-TRIAL FOR COMPLEX PARTIAL SEIZURES SO EPILEPSIA LA English DT Article DE EPILEPSY; COMPLEX PARTIAL SEIZURES; FELBAMATE ID PHENYTOIN; DRUGS AB We performed a randomized, double-blind, three-period cross-over study of felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate: Carter-Wallace 554) in patients with complex partial seizures. Patients continued carbamazepine (CBZ) throughout the study and were observed in the hospital for the entire trial period. The entry criteria required at least six seizures in a 3-week baseline period (and no more than 1 week with a single seizure) with CBZ alone. Thirty subjects were randomized. Two left the study after randomization, 1 owing to seizure exacerbation, and 1 owing to hyponatremia, which may have been related to CBZ therapy. The daily dosage of 50 mg/kg (maximum 3,000 mg) FBM per day was well tolerated by all 28 patients who completed the study. Only mild adverse experiences were observed during the trial. FBM reduced CBZ level (p < 0.0001; 95% confidence interval -28%, -20%). There was no significant difference in seizure frequency between placebo and FBM periods (one-sided p = 0.172), but when a correction was made for the lower CBZ level noted during FBM periods, the data suggested a strong antiseizure effect of FBM. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH DIR,BETHESDA,MD 20892. RP THEODORE, WH (reprint author), NINCDS,MED NEUROL BRANCH,CLIN EPILEPSY SECT,BLDG 10,ROOM 5N-248,BETHESDA,MD 20892, USA. RI Nice, Frank/A-6909-2009 NR 16 TC 121 Z9 121 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY-JUN PY 1991 VL 32 IS 3 BP 392 EP 397 DI 10.1111/j.1528-1157.1991.tb04668.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA FR169 UT WOS:A1991FR16900016 PM 2044501 ER PT J AU LEIDERMAN, DB BALISH, M BROMFIELD, EB THEODORE, WH AF LEIDERMAN, DB BALISH, M BROMFIELD, EB THEODORE, WH TI EFFECT OF VALPROATE ON HUMAN CEREBRAL GLUCOSE-METABOLISM SO EPILEPSIA LA English DT Article DE CEREBRAL GLUCOSE METABOLISM; EPILEPSY; SEIZURES; ANTICONVULSANTS; CARBAMAZEPINE; VALPROATE ID POTASSIUM CONDUCTANCE; SODIUM VALPROATE; ACID; CARBAMAZEPINE; CHILDREN; MUSCIMOL; NEURONS; AGONIST; DRUGS AB We studied the effects of valproate (VPA) on local cerebral glucose metabolism (LCMRglc) in eight patients with partial seizure disorders and two with primary generalized epilepsy. Each patient had two positron-emission tomography (PET) scans with F-18-2-deoxyglucose (FDG), with, and without, VPA (mean level 52 mg/dl, range 30-127 mg/dl). Patients continued carbamazepine (CBZ) for both scans; serum concentrations were not significantly changed by VPA (CBZ range 5.4-12 mg/dl). Seven patients had the "without-VPA" scan first. Mean interval between PET scans was 75 days. Global CMRglc was decreased by 22% by addition of VPA (7.2 +/- 1.8 mg/100 g/min without VPA, 5.6 +/- 1.1 g/min with VPA, p < 0.05, corrected). Thirteen regions of interest (ROIs) were analyzed in each hemisphere in each PET scan. Metabolic rates were significantly lower in 15 of 26 ROIs with VPA (p < 0.05, corrected). VPA depresses cerebral metabolism to a greater degree than do CBZ and phenytoin (PHT) but less than does phenobarbital (PB). The metabolic effect may be related to the mechanism of action and have neuropsychological implications. C1 NINCDS,MED NEUROL BRANCH,CLIN EPILEPSY SECT,BETHESDA,MD 20892. NR 28 TC 80 Z9 80 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY-JUN PY 1991 VL 32 IS 3 BP 417 EP 422 DI 10.1111/j.1528-1157.1991.tb04671.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA FR169 UT WOS:A1991FR16900019 PM 2044503 ER PT J AU BROMFIELD, EB LUDLOW, CL SEDORY, S LEIDERMAN, DB THEODORE, WH AF BROMFIELD, EB LUDLOW, CL SEDORY, S LEIDERMAN, DB THEODORE, WH TI CEREBRAL ACTIVATION DURING SPEECH-DISCRIMINATION IN TEMPORAL-LOBE EPILEPSY SO EPILEPSY RESEARCH LA English DT Article DE TOMOGRAPHY, POSITRON EMISSION; EPILEPSY; AUDITORY DISCRIMINATION ID GLUCOSE-METABOLISM; AUDITORY-STIMULATION; EEG AB Eight patients with uncontrolled complex partial seizures underwent positron emission tomography with 18-fluoro-2-deoxyglucose both at rest and during an auditory order discrimination task using speech syllables. Eight age-matched controls were scanned under identical conditions; an additional 18 normal subjects were scanned only at rest. No consistent task-related changes were seen in control subjects. For the 3 patients with left temporal epileptogenic foci, left inferior temporal lobe hypometabolism was more evident during the activated than during the resting scan. Activation procedures may augment the diagnostic yield of metabolic scanning in epilepsy. C1 NATL INST DEAFNESS & OTHER COMMUN DISORDERS,BETHESDA,MD. NATL INST NEUROL DIS & STROKE,MED NEUROL BRANCH,CLIN EPILEPSY SECT,BETHESDA,MD. OI Ludlow, Christy/0000-0002-2015-6171 NR 22 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAY-JUN PY 1991 VL 9 IS 1 BP 49 EP 58 DI 10.1016/0920-1211(91)90046-I PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA FU921 UT WOS:A1991FU92100006 PM 1884717 ER PT J AU SEDER, RA LEGROS, G BENSASSON, SZ URBAN, J FINKELMAN, FD PAUL, WE AF SEDER, RA LEGROS, G BENSASSON, SZ URBAN, J FINKELMAN, FD PAUL, WE TI INCREASED FREQUENCY OF INTERLEUKIN-4-PRODUCING T-CELLS AS A RESULT OF POLYCLONAL PRIMING - USE OF A SINGLE-CELL ASSAY TO DETECT INTERLEUKIN-4-PRODUCING CELLS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID SECRETING MURINE PLASMACYTOMAS; IGD MYELOMA PROTEINS; MONOCLONAL-ANTIBODY; LYMPHOKINE ACTIVITIES; INDEPENDENT ANTIGEN; H-2 RECOGNITION; IDENTIFICATION; IL-4; ACTIVATION; POLYPEPTIDE AB A limiting dilution assay capable of detecting interleukin 4 (IL4) production by a single cell has been developed. This assay is based on the stimulation of T cells, in the presence of IL 2 (5 U/ml), with anti-CD3 antibody bound to the surface of Terasaki wells. Cells of the IL 4-selective indicator line, CT.4S, are added 24-36 h later and IL 4 production is determined based on their survival 24-48 h thereafter. A frequency of 0.98 was obtained for IL 4 production by T cells of the D10.G4 cell line. T cells from naive donors capable of producing IL 4 in response to anti-CD3 plus IL 2 were quite rare, with a frequency in four experiments ranging between 0.0003 and 0.0018. Treatment of mice with polyclonal activators known to increase the IL 4-producing capacity of T cells when assayed in bulk culture caused striking increases in the frequency of IL 4-producing cells. Similarly, culturing cells in vitro with anti-CD3, IL 2 and IL 4 for 5 days caused a marked increase in the frequency of cells capable of producing IL 4, to 0.031.IL 4 production by individual T cells is dependent upon IL 2. Thus, in naive T cell populations, the frequency of IL 4-producing cells in response to stimulation with anti-CD3 in the absence of IL 2 was below the limit of detection. T cells from primed donors showed a striking inhibition in the frequency of IL 4-producing cells in response to anti-CD3 when IL 2 was not present. The availability of a simple assay to measure the frequency of cells capable of producing IL 4 should have substantial utility in allowing the evaluation of conditions that regulate IL 4 production in vivo and in vitro. C1 HEBREW UNIV JERUSALEM,HADASSAH MED CTR,LAUTENBERG CTR TUMOR IMMUNOL,JERUSALEM,ISRAEL. USDA,BELTSVILLE,MD 20705. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. RP SEDER, RA (reprint author), NIAID,IMMUNOL LAB,BLDG 10,RM 11N311,BETHESDA,MD 20892, USA. RI Le Gros, Graham/C-6725-2011; OI Urban, Joseph/0000-0002-1590-8869 NR 22 TC 51 Z9 51 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 MAY PY 1991 VL 21 IS 5 BP 1241 EP 1247 DI 10.1002/eji.1830210522 PG 7 WC Immunology SC Immunology GA FM553 UT WOS:A1991FM55300021 PM 1828031 ER PT J AU HORTON, WE HIGGINBOTHAM, JD AF HORTON, WE HIGGINBOTHAM, JD TI SULFOXIDE STIMULATION OF CHONDROGENESIS IN LIMB MESENCHYME IS ACCOMPANIED BY AN INCREASE IN TYPE-II COLLAGEN ENHANCER ACTIVITY SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID GROWTH FACTOR-BETA; DIFFERENTIATION; CELLS; EXPRESSION C1 ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46285. RP HORTON, WE (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 19 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY PY 1991 VL 194 IS 1 BP 100 EP 104 DI 10.1016/0014-4827(91)90136-I PG 5 WC Oncology; Cell Biology SC Oncology; Cell Biology GA FG024 UT WOS:A1991FG02400015 PM 2015842 ER PT J AU SMITH, SB OBRIEN, PJ AF SMITH, SB OBRIEN, PJ TI ACYLATION AND GLYCOSYLATION OF RHODOPSIN IN THE RD MOUSE SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE RHODOPSIN; RETINA; RETINAL DEGENERATION; RD MOUSE; ACYLATION; GLYCOSYLATION ID BOVINE RHODOPSIN; RETINAL DEGENERATION; PHOTORECEPTOR CELLS; MUTANT MICE; PROTEINS; BINDING; BIOSYNTHESIS; GLYCOPROTEIN; OLIGOSACCHARIDES; CARBOHYDRATE RP SMITH, SB (reprint author), NEI,RETINA CELL & MOLEC BIOL LAB,BLDG 6,ROOM B1A04,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY 06859] NR 43 TC 6 Z9 6 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 MAY PY 1991 VL 52 IS 5 BP 599 EP 606 DI 10.1016/0014-4835(91)90062-J PG 8 WC Ophthalmology SC Ophthalmology GA FP331 UT WOS:A1991FP33100014 PM 2065728 ER PT J AU RUSSELL, P AF RUSSELL, P TI 2-DIMENSIONAL GEL-ELECTROPHORESIS OF HUMAN LENS EPITHELIUM - A STUDY OF SPATIAL PROTEIN-PATTERNS AND AGING SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE LENS; EPITHELIUM; GEL ELECTROPHORESIS; AGING; CRYSTALLINS ID AGE-RELATED-CHANGES; TISSUE-CULTURE; CELLS; CRYSTALLIN; FETAL; MORPHOLOGY; EXPRESSION RP RUSSELL, P (reprint author), NEI,BLDG 6,RM 228,BETHESDA,MD 20892, USA. NR 17 TC 7 Z9 7 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 MAY PY 1991 VL 52 IS 5 BP 613 EP 618 DI 10.1016/0014-4835(91)90064-L PG 6 WC Ophthalmology SC Ophthalmology GA FP331 UT WOS:A1991FP33100016 PM 2065730 ER PT J AU KIMES, AS LONDON, ED SZABO, G RAYMON, L TABAKOFF, B AF KIMES, AS LONDON, ED SZABO, G RAYMON, L TABAKOFF, B TI REDUCTION OF CEREBRAL GLUCOSE-UTILIZATION BY THE HIV ENVELOPE GLYCOPROTEIN-GP-120 SO EXPERIMENTAL NEUROLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; VASOACTIVE INTESTINAL PEPTIDE; T4 ANTIGEN; HTLV-III; MORPHINE WITHDRAWAL; DEMENTIA COMPLEX; RECEPTOR-BINDING; AIDS PATIENTS; CD4 RECEPTOR; GLIAL-CELLS C1 NIAAA,INTRAMURAL RES PROGRAM,SPECIAL PROJECTS UNIT,BETHESDA,MD 20892. RP KIMES, AS (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,NEUROPHARMACOL LAB,BALTIMORE,MD 21224, USA. NR 40 TC 30 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 1991 VL 112 IS 2 BP 224 EP 228 DI 10.1016/0014-4886(91)90073-L PG 5 WC Neurosciences SC Neurosciences & Neurology GA FJ614 UT WOS:A1991FJ61400011 PM 2037031 ER PT J AU LI, J ZHU, JD APPIAH, A MCCUTCHAN, TF LONG, GW MILHOUS, WK HOLLINGDALE, MR AF LI, J ZHU, JD APPIAH, A MCCUTCHAN, TF LONG, GW MILHOUS, WK HOLLINGDALE, MR TI PLASMODIUM-BERGHEI - QUANTITATION OF INVITRO EFFECTS OF ANTIMALARIAL-DRUGS ON EXOERYTHROCYTIC DEVELOPMENT BY A RIBOSOMAL-RNA PROBE SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE PLASMODIUM-BERGHEI; MALARIA; RIBOSOMAL-RNA PROBE; MALARIAL CHEMOTHERAPY; INVITRO DRUG ASSAY; RIBOSOMAL RNA (RIBOSOMAL-RNA); EXOERYTHROCYTIC (EE); 50-PERCENT INHIBITORY CONCENTRATION (IC50); PRIMAQUINE (PQ) PYRIMETHAMINE (PYR); CHLOROQUINE (CQ); STANDARD SALINE CITRATE (SSC) ID STAGE; POPULATIONS; CULTIVATION; SPOROZOITES; FALCIPARUM; DIAGNOSIS; CULTURE; MALARIA C1 BIOMED RES INST, ROCKVILLE, MD 20852 USA. NIAID, PARASIT DIS LAB, BETHESDA, MD 20892 USA. USN, DEPT INFECT DIS, DIV MALARIA, BETHESDA, MD 20814 USA. WALTER REED ARMY MED CTR, DEPT PARASITOL, DIV EXPTL THERAPEUT, WASHINGTON, DC 20307 USA. RP LI, J (reprint author), SECOND MIL MED UNIV, 594 XIANG YIN RD, SHANGHAI, PEOPLES R CHINA. NR 21 TC 13 Z9 13 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 0014-4894 EI 1090-2449 J9 EXP PARASITOL JI Exp. Parasitol. PD MAY PY 1991 VL 72 IS 4 BP 450 EP 458 DI 10.1016/0014-4894(91)90091-A PG 9 WC Parasitology SC Parasitology GA FK855 UT WOS:A1991FK85500013 PM 2026219 ER PT J AU LOURIE, IS KATZLEAVY, J AF LOURIE, IS KATZLEAVY, J TI NEW DIRECTIONS FOR MENTAL-HEALTH-SERVICES FOR FAMILIES AND CHILDREN SO FAMILIES IN SOCIETY-THE JOURNAL OF CONTEMPORARY HUMAN SERVICES LA English DT Article C1 GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20057. RP LOURIE, IS (reprint author), NIMH,CHILD & FAMILY SUPPORT BRANCH,ROCKVILLE,MD 20857, USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU FAMILY SERVICE AMER PI MILWAUKEE PA 11700 WEST LAKE PARK DRIVE, MILWAUKEE, WI 53224 SN 1044-3894 J9 FAM SOC-J CONTEMP H JI Fam. Soc.-J. Contemp. Hum. Serv. PD MAY PY 1991 VL 72 IS 5 BP 277 EP 285 PG 9 WC Family Studies; Social Work SC Family Studies; Social Work GA FJ447 UT WOS:A1991FJ44700004 ER PT J AU SEI, Y MCINTYRE, T FRIDE, E YOSHIMOTO, K SKOLNICK, P ARORA, PK AF SEI, Y MCINTYRE, T FRIDE, E YOSHIMOTO, K SKOLNICK, P ARORA, PK TI INHIBITION OF CALCIUM MOBILIZATION IS AN EARLY EVENT IN OPIATE-INDUCED IMMUNOSUPPRESSION SO FASEB JOURNAL LA English DT Article DE OPIATES; OPIATE, RECEPTORS; CENTRAL NERVOUS SYSTEM; CALCIUM MOBILIZATION; T-CELLS; B-CELLS; IMMUNOSUPPRESSION ID FLUORESCENT INDICATORS; BETA-ENDORPHIN; MORPHINE; MICE; IMMUNOMODULATION; LYMPHOCYTES; CELLS AB Morphine administered as a subcutaneous implant inhibits the initial increase in cytoplasmic free-calcium [Ca2+]i induced by mitogens in mouse splenocytes. This effect was not reproduced by incubation of splenocytes with morphine (10(-8)-10(-4) M). Analysis of splenocyte subpopulations demonstrates that this effect was manifest in both B and T cells. However, within T cell subpopulations, CD4+ but not CD8+ cells were affected. Adrenalectomy abolished this effect of morphine in CD4+ T but not CD4-, CD8- spleen cells (most likely Thy 1.2- B cells). Moreover, simultaneous administration of the opiate antagonist naltrexone blocked the effect of morphine in CD4-, CD8- spleen cells, but not in CD4+ T cells. These data indicate that the effects of morphine on mitogen-stimulated increase in [Ca2+]i may be mediated through distinct glucocorticoid-dependent and -independent mechanisms. The morphine-induced inhibition of an increase in [Ca2+]i in immune cells reported here may be an early event mediating opiate-induced immunosuppression. C1 NIDDKD,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 28 TC 33 Z9 34 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 1991 VL 5 IS 8 BP 2194 EP 2199 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA FK111 UT WOS:A1991FK11100012 PM 2022315 ER PT J AU YANG, XC KARSCHIN, A LABARCA, C ELROYSTEIN, O MOSS, B DAVIDSON, N LESTER, HA AF YANG, XC KARSCHIN, A LABARCA, C ELROYSTEIN, O MOSS, B DAVIDSON, N LESTER, HA TI EXPRESSION OF ION CHANNELS AND RECEPTORS IN XENOPUS OOCYTES USING VACCINIA VIRUS SO FASEB JOURNAL LA English DT Article DE XENOPUS OOCYTES; HETEROLOGOUS EXPRESSION; ION CHANNELS; NEUROTRANSMITTER RECEPTORS; VACCINIA VIRUS ID POTASSIUM CHANNELS; CDNA; SYSTEM; RAT; DROSOPHILA; CLONING; BRAIN AB The cytoplasmic injection of mRNA synthesized in vitro into Xenopus oocytes is widely used for heterologous expression of ion channels and neurotransmitter receptors. We report two new methods for expression of ion channels and receptors in oocytes using vaccinia virus (VV). 1) A recombinant VV carrying the Shaker H4 K+ channel cDNA driven by the VV P7.5 early promoter was injected into oocytes. 2) A recombinant VV containing the bacteriophage T7 RNA polymerase driven by the P7.5 promoter was coinjected along with plasmids containing a T7 promoter and cDNAs for channels and receptors. The functionally expressed proteins include a) voltage-gated ion channels: the Shaker H4 K+ channel and the rat brain IIA Na+ channel, b) a ligand-gated ion channel: the mouse muscle nicotinic acetylcholine receptor (AChR), and c) a G protein-coupled receptor: the rat brain 5HT1C receptor. After virus/cDNA injection into oocytes, these channels and receptors generally showed characteristics and expression levels similar to those observed in mRNA-injected oocytes. However, the AChR expressed at lower levels in virus/cDNA-injected oocytes than in mRNA-injected oocytes. Because our methods bypass mRNA synthesis, they are more rapid and convenient than the mRNA injection method. Potential applications to structure-function studies and expression cloning are discussed. C1 CALTECH,DIV BIOL 156-29,PASADENA,CA 91125. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM-10991]; NINDS NIH HHS [NS-11756] NR 22 TC 12 Z9 12 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 1991 VL 5 IS 8 BP 2209 EP 2216 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA FK111 UT WOS:A1991FK11100014 PM 1708738 ER PT J AU WILLIAMS, J GLADEN, BC TURNER, TW SCHRADER, SM CHAPIN, RE AF WILLIAMS, J GLADEN, BC TURNER, TW SCHRADER, SM CHAPIN, RE TI THE EFFECTS OF ETHYLENE DIBROMIDE ON SEMEN QUALITY AND FERTILITY IN THE RABBIT - EVALUATION OF A MODEL FOR HUMAN SEMINAL CHARACTERISTICS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID WORKERS; DIBROMOCHLOROPROPANE; PLASMA; BULLS; RATS C1 NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. NIEHS,NATL TOXICOL PROGRAM,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. NIOSH,EXPTL TOXICOL BRANCH,CINCINNATI,OH 45226. RI Schrader, Steven/E-8120-2011; OI Chapin, Robert/0000-0002-5997-1261 FU PHS HHS [IR920859] NR 41 TC 14 Z9 14 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1991 VL 16 IS 4 BP 687 EP 700 DI 10.1016/0272-0590(91)90155-W PG 14 WC Toxicology SC Toxicology GA FJ691 UT WOS:A1991FJ69100006 PM 1884910 ER PT J AU SCHWETZ, BA MAST, TJ WEIGEL, RJ DILL, JA MORRISSEY, RE AF SCHWETZ, BA MAST, TJ WEIGEL, RJ DILL, JA MORRISSEY, RE TI DEVELOPMENTAL TOXICITY OF INHALED METHYL ETHYL KETONE IN SWISS MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID N-BUTYL KETONE; RATS; EMBRYOTOXICITY; FETOTOXICITY; INHALATION C1 NIEHS, DIV TOXICOL RES & TESTING, DEV & REPROD TOXICOL GRP, RES TRIANGLE PK, NC 27709 USA. PACIFIC NW LAB, RICHLAND, WA 99352 USA. NR 17 TC 8 Z9 8 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1991 VL 16 IS 4 BP 742 EP 748 DI 10.1016/0272-0590(91)90160-6 PG 7 WC Toxicology SC Toxicology GA FJ691 UT WOS:A1991FJ69100011 PM 1884913 ER PT J AU TRYPHONAS, H LUSTER, MI SCHIFFMAN, G DAWSON, LL HODGEN, M GERMOLEC, D HAYWARD, S BRYCE, F LOO, JCK MANDY, F ARNOLD, DL AF TRYPHONAS, H LUSTER, MI SCHIFFMAN, G DAWSON, LL HODGEN, M GERMOLEC, D HAYWARD, S BRYCE, F LOO, JCK MANDY, F ARNOLD, DL TI EFFECT OF CHRONIC EXPOSURE OF PCB (AROCLOR-1254) ON SPECIFIC AND NONSPECIFIC IMMUNE PARAMETERS IN THE RHESUS (MACACA-MULATTA) MONKEY SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID POLYCHLORINATED-BIPHENYLS PCBS; IMMUNOLOGICAL EVALUATION; ANTIBODY-RESPONSE; AH RECEPTOR; IMMUNOTOXICITY; MICE; SUPPRESSION; TOXICITY; CELLS; RAT C1 NIEHS,IMMUNOTOXICOL GRP,RES TRIANGLE PK,NC 27709. SUNY DOWNSTATE MED CTR,HLTH SCI CTR,BROOKLYN,NY 11794. RP TRYPHONAS, H (reprint author), HLTH & WELF CANADA,HLTH PROTECT BRANCH,FOOD DIRECTORATE,BUR CHEM SAFETY,DIV TOXICOL RES,OTTAWA K1A 0L2,ONTARIO,CANADA. FU FDA HHS [5U01-FD-01217-02, FD 226-80-0003-01]; PHS HHS [N01 026427] NR 37 TC 82 Z9 85 U1 0 U2 6 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 MAY PY 1991 VL 16 IS 4 BP 773 EP 786 DI 10.1016/0272-0590(91)90163-X PG 14 WC Toxicology SC Toxicology GA FJ691 UT WOS:A1991FJ69100014 PM 1884915 ER PT J AU HEDLUND, LW MARONPOT, RR JOHNSON, GA COFER, GP MILLS, GI WHEELER, CT AF HEDLUND, LW MARONPOT, RR JOHNSON, GA COFER, GP MILLS, GI WHEELER, CT TI MAGNETIC-RESONANCE MICROSCOPY OF TOXIC RENAL INJURY INDUCED BY BROMOETHYLAMINE IN RATS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID PAPILLARY NECROSIS; MR MICROSCOPY; KIDNEY; THORAX C1 NIEHS,RES TRIANGLE PK,NC 27709. RP HEDLUND, LW (reprint author), DUKE UNIV,MED CTR,DEPT RADIOL,DURHAM,NC 27710, USA. OI Johnson, G.Allan/0000-0002-7606-5447; Hedlund, Laurence/0000-0001-5275-0397 NR 27 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1991 VL 16 IS 4 BP 787 EP 797 DI 10.1016/0272-0590(91)90164-Y PG 11 WC Toxicology SC Toxicology GA FJ691 UT WOS:A1991FJ69100015 PM 1884916 ER PT J AU WHANGPENG, J KNUTSEN, T GAZDAR, A STEINBERG, SM OIE, H LINNOILA, I MULSHINE, J NAU, M MINNA, JD AF WHANGPENG, J KNUTSEN, T GAZDAR, A STEINBERG, SM OIE, H LINNOILA, I MULSHINE, J NAU, M MINNA, JD TI NONRANDOM STRUCTURAL AND NUMERICAL CHROMOSOME CHANGES IN NON-SMALL-CELL LUNG-CANCER SO GENES CHROMOSOMES & CANCER LA English DT Article ID MYC GENE FAMILY; K-RAS ONCOGENE; CYTOGENETIC ABNORMALITIES; SHORT ARM; MALIGNANT MESOTHELIOMA; BANDING-PATTERNS; DNA-SEQUENCE; WILMS-TUMOR; CARCINOMA; EXPRESSION AB Cytogenetic studies were performed on 27 tumor cell lines (most of which were derived from metastatic lesions) and four fresh malignant pleural and pericardial effusions from 30 patients with non-small-cell lung cancer (non-SCLC). Many clonal structural (deletions and nonreciprocal translocations) and numerical abnormalities were found in each specimen. Statistical analysis revealed these changes were nonrandomly distributed among the chromosomes. A statistically significant number of chromosomal breakpoints were seen in regions 1q1, 1q3, 3p1, 3p2, 3q1, 3q2, 7q1, 13p1, 14p1, 15p1, and 17q1 when the regions were compared to the total haploid complement. In addition, when a given region was compared to other regions within the same chromosome, statistically significant numbers of breakpoints were noted for regions 1q3, 5q1, 7q1, 13p1, 14p1, 15p1, 16q2, 17q1, and 21p1. Specific chromosome bands showing the most frequent involvement in structural abnormalities were (in descending order) 3p14.2, 3q21, 19q13, 11p15, 1q11, 7q11, 1q21, 3p23, and 3p21. The breakpoints indicate areas to look for new dominant oncogenes activated by translocations, while the areas of deletions and loss of material by nonreciprocal translocations highlight areas to search for recessive oncogenes. These cytogenetic studies represent strong evidence that multiple genetic lesions are associated with the development of metastatic lung cancer, and provide a roadmap to search for new genes involved in the pathogenesis of lung cancer. C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NCI,DIV CANC TREATMENT,COP,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20892. NR 79 TC 108 Z9 108 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 MAY PY 1991 VL 3 IS 3 BP 168 EP 188 DI 10.1002/gcc.2870030303 PG 21 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA FR181 UT WOS:A1991FR18100002 PM 1651103 ER PT J AU KWAN, SP LEHNER, T HAGEMANN, T LU, B BLAESE, M OCHS, H WEDGWOOD, R OTT, J CRAIG, IW ROSEN, FS AF KWAN, SP LEHNER, T HAGEMANN, T LU, B BLAESE, M OCHS, H WEDGWOOD, R OTT, J CRAIG, IW ROSEN, FS TI LOCALIZATION OF THE GENE FOR THE WISKOTT-ALDRICH SYNDROME BETWEEN 2 FLANKING MARKERS, TIMP AND DXS255, ON XP11.22-XP11.3 SO GENOMICS LA English DT Article ID HUMAN X-CHROMOSOME; LYMPHOCYTE SURFACE SIALOGLYCOPROTEIN; DUCHENNE MUSCULAR-DYSTROPHY; LINKED AGAMMAGLOBULINEMIA; LINKAGE ANALYSIS; LOCUS; RFLP; POLYMORPHISMS; ABNORMALITIES; COMMITTEE C1 NCI,BETHESDA,MD 20014. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. UNIV OXFORD,GENET LAB,OXFORD OX1 3QU,ENGLAND. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY 10027. RP KWAN, SP (reprint author), RUSH MED SCH,DEPT IMMUNOL,CHICAGO,IL 60612, USA. FU NCRR NIH HHS [RR2172]; NIAID NIH HHS [AI21163, AI25117] NR 32 TC 56 Z9 57 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 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1991 VL 10 IS 1 BP 29 EP 33 DI 10.1016/0888-7543(91)90480-3 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FK408 UT WOS:A1991FK40800005 PM 1675197 ER PT J AU TZIMAGIORGIS, G ADAMSON, MC KOZAK, CA MOSCHONAS, NK AF TZIMAGIORGIS, G ADAMSON, MC KOZAK, CA MOSCHONAS, NK TI CHROMOSOMAL MAPPING OF GLUTAMATE-DEHYDROGENASE GENE-SEQUENCES TO MOUSE CHROMOSOME-7 AND CHROMOSOME-14 SO GENOMICS LA English DT Article ID NEUROLOGICAL DISORDERS; DEFICIENCY; BRAIN C1 FDN RES & TECHNOL,INST MOLEC BIOL & BIOTECHNOL,POB 1527,GR-71110 HERAKLION,GREECE. UNIV CRETE,DEPT BIOL,GR-71110 HERAKLION,GREECE. NIAID,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 29 TC 15 Z9 15 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 MAY PY 1991 VL 10 IS 1 BP 83 EP 88 DI 10.1016/0888-7543(91)90487-Y PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FK408 UT WOS:A1991FK40800012 PM 2045113 ER PT J AU WHITE, MB KRUEGER, LJ HOLSCLAW, DS GERRARD, BC STEWART, C QUITTELL, L DOLGANOV, G BARANOV, V IVASCHENKO, T KAPRONOV, NI SEBASTIO, G CASTIGLIONE, O DEAN, M AF WHITE, MB KRUEGER, LJ HOLSCLAW, DS GERRARD, BC STEWART, C QUITTELL, L DOLGANOV, G BARANOV, V IVASCHENKO, T KAPRONOV, NI SEBASTIO, G CASTIGLIONE, O DEAN, M TI DETECTION OF 3 RARE FRAMESHIFT MUTATIONS IN THE CYSTIC-FIBROSIS GENE IN AN AFRICAN-AMERICAN (CF444DELA), AN ITALIAN (CF2522INSC), AND A SOVIET (CF3821DELT) SO GENOMICS LA English DT Note ID POLYMERASE CHAIN-REACTION; DNA C1 MOSCOW PEDIAT INST,MOSCOW,USSR. NAPLES UNIV,I-80138 NAPLES,ITALY. FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD. LENINGRAD OBSTET INST,LENINGRAD,USSR. HAHNEMANN UNIV,PHILADELPHIA,PA 19102. COLUMBIA UNIV,MED CTR,NEW YORK,NY 10027. MM SHEMYAKIN BIOORGAN CHEM INST,MOSCOW 117312,USSR. RP WHITE, MB (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU PHS HHS [N01-C0-74102] NR 9 TC 33 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1991 VL 10 IS 1 BP 266 EP 269 DI 10.1016/0888-7543(91)90510-L PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FK408 UT WOS:A1991FK40800035 PM 1710600 ER PT J AU BALE, AE MITCHELL, AL GONZALEZ, FJ MCBRIDE, OW AF BALE, AE MITCHELL, AL GONZALEZ, FJ MCBRIDE, OW TI LOCALIZATION OF CYP2F1 BY MULTIPOINT LINKAGE ANALYSIS AND PULSED-FIELD GEL-ELECTROPHORESIS SO GENOMICS LA English DT Note ID CYTOCHROME-P-450 GENE; CHROMOSOME-19; SUBFAMILIES; IIB C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP BALE, AE (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 13 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1991 VL 10 IS 1 BP 284 EP 286 DI 10.1016/0888-7543(91)90514-F PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FK408 UT WOS:A1991FK40800039 PM 2045106 ER PT J AU IVASCHENKO, TE WHITE, MB DEAN, M BARANOV, VS AF IVASCHENKO, TE WHITE, MB DEAN, M BARANOV, VS TI A DELETION OF 2 NUCLEOTIDES IN EXON-10 OF THE CFTR GENE IN A SOVIET FAMILY WITH CYSTIC-FIBROSIS CAUSING EARLY INFANT DEATH SO GENOMICS LA English DT Note ID MUTATIONS C1 PROGRAM RESOURCES INC,DYNCORP,FREDERICK CANC RES & DEV CTR,POB B,FREDERICK,MD 21702. ACAD MED SCI USSR,INST OBSTET & GYNECOL,CTR PRENATAL DIAG CYST FIBROSIS,LENINGRAD 199034,USSR. NCI,FREDERICK CANC RES & DEV CTR,VIROL CARCINOGENESIS LAB,FREDERICK,MD 21701. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-74102] NR 8 TC 32 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 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1991 VL 10 IS 1 BP 298 EP 299 DI 10.1016/0888-7543(91)90517-I PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FK408 UT WOS:A1991FK40800042 PM 1710601 ER PT J AU COLLINS, JL LUTZ, RJ AF COLLINS, JL LUTZ, RJ TI INVITRO STUDY OF SIMULTANEOUS INFUSION OF INCOMPATIBLE DRUGS IN MULTILUMEN CATHETERS SO HEART & LUNG LA English DT Article AB Multilumen catheters are commonly used to simultaneously administer incompatible drugs to critically ill patients. Though there are no known documented reports that this practice has been responsible for harmful events in patients, likewise there are no published data to verify the safety and efficacy of this practice. This study utilized an in vitro model flow system to examine the physicochemical phenomena that occur when two incompatible drugs (phenytoin and total parenteral nutrition) are simultaneously administered through multilumen catheters. Flow conditions and drug infusions in the venous model were designed to mimic the in vivo clinical situation to evaluate two central venous catheter types, a double- and a triple-lumen catheter. Video recordings were made of drug interactions, and assays of phenytoin concentration were performed on samples of the circulating fluid. White clouds of phenytoin precipitation were observed near the tip of the double-lumen catheter but not the triple-lumen catheter. Infusion through the double-lumen catheter resulted in an average of 6% loss of phenytoin to precipitate, which, on microscopic examination, appeared as spindle-shaped crystals 25 to 50-mu-m in length and 5 to 10-mu-m wide. In some cases, millimeter-size fragments of phenytoin precipitate were seen to dislodge from the tip of the double-lumen catheter. The adjacent orifices at the tip of the end hole of the double-lumen catheter appeared to permit interaction of the two effusing streams of the incompatible drugs, whereas the staggered orifices of the triple-lumen catheter reduce this interaction. The clinical significance of the precipitate incompatibility has yet to be assessed, but possible complications may include reduced bioavailability of drug, thrombophlebitis from particulates, pulmonary emboli from larger precipitate fragments, and catheter occlusion. C1 NIH,CANC NURSING SERV,BLDG 13,ROOM 3W13,BETHESDA,MD 20892. NR 0 TC 9 Z9 9 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0147-9563 J9 HEART LUNG JI Heart Lung PD MAY PY 1991 VL 20 IS 3 BP 271 EP 277 PG 7 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA FN317 UT WOS:A1991FN31700010 PM 1903369 ER PT J AU PETERS, M VIERLING, J GERSHWIN, ME MILICH, D CHISARI, FV HOOFNAGLE, JH AF PETERS, M VIERLING, J GERSHWIN, ME MILICH, D CHISARI, FV HOOFNAGLE, JH TI IMMUNOLOGY AND THE LIVER SO HEPATOLOGY LA English DT Article ID HEPATITIS-B VIRUS; PRIMARY BILIARY-CIRRHOSIS; CHRONIC ACTIVE HEPATITIS; INTERFERON-INDUCED TRANSCRIPTION; NECROSIS-FACTOR-ALPHA; CORE ANTIGEN HBCAG; VS-HOST DISEASE; DIHYDROLIPOAMIDE ACETYLTRANSFERASE; T-CELLS; AUTOIMMUNE HEPATITIS C1 NIH,DIV DIGEST DIS & NUTR,BLDG 31,ROOM 9A23,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DIV GASTROENTEROL,ST LOUIS,MO 63110. CEDARS SINAI MED CTR,DIV HEPATOL,LOS ANGELES,CA 90048. UNIV CALIF DAVIS,SCH MED,DIV RHEUMATOL ALLERGY & CLIN IMMUNOL,DAVIS,CA 95616. SCRIPPS CLIN & RES FDN,GEN CLIN RES CTR,LA JOLLA,CA 92037. RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044 NR 113 TC 135 Z9 140 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1991 VL 13 IS 5 BP 977 EP 994 DI 10.1016/0270-9139(91)90273-X PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA FM340 UT WOS:A1991FM34000028 PM 2030002 ER PT J AU OKA, H IKAI, Y KAWAMURA, N YAMADA, M HAYAKAWA, J HARADA, K NAGASE, K MURATA, H SUZUKI, M ITO, Y AF OKA, H IKAI, Y KAWAMURA, N YAMADA, M HAYAKAWA, J HARADA, K NAGASE, K MURATA, H SUZUKI, M ITO, Y TI OPTIMIZATION OF A HIGH-SPEED COUNTERCURRENT CHROMATOGRAPH FOR ANALYTICAL SEPARATIONS SO HRC-JOURNAL OF HIGH RESOLUTION CHROMATOGRAPHY LA English DT Article DE HIGH SPEED COUNTERCURRENT CHROMATOGRAPHY; 2-PHASE SOLVENT SYSTEM; COLUMN DIAMETER; OPTIMIZATION; INDOLE AUXINS ID COIL PLANET CENTRIFUGE; MASS-SPECTROMETRY; NATURAL-PRODUCTS AB The analytical capability of the high speed countercurrent chromatograph model 4000 (HSCCC-4000) has been improved by optimizing the dimensions of the multilayer coiled column. Using a two-phase solvent system of n-hexane-ethyl acetate - methanol - water (1:1:1:1) and a set of indole auxins as test samples, a series of studies was conducted to evaluate performance of coiled columns with i.d.s ranging from 0.1 to 0.55 mm. The studies on the stationary phase retention indicated that multilayer coils of 0.55 mm and 0.30 mm i.d. provide satisfactory retention of the stationary phase while the 0.10 mm i.d. column fails to yield reproducible retention. The best partition efficiencies were obtained from the 0.30 mm i.d. multilayer coil with a 6 ml capacity which produced theoretical plate numbers ranging from 5500 to 10500 with a resolution factor of 2.30. The feasibility of interfacing the HSCCC-4000 with a mass spectrometer is briefly discussed. C1 MEIJO UNIV,FAC PHARM,NAGOYA,AICHI 468,JAPAN. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP OKA, H (reprint author), AICHI PREFECTURAL INST PUBL HLTH,KITA KU,NAGOYA 462,JAPAN. NR 7 TC 3 Z9 3 U1 0 U2 4 PU DR ALFRED HUTHIG VERLAG GMBH PI HEIDELBERG 1 PA POSTFACH 102869, W-69018 HEIDELBERG 1, GERMANY SN 0935-6304 J9 HRC-J HIGH RES CHROM JI HRC-J. High Resolut. Chromatogr. PD MAY PY 1991 VL 14 IS 5 BP 306 EP 311 PG 6 WC Chemistry, Analytical SC Chemistry GA FT016 UT WOS:A1991FT01600002 ER PT J AU BROOK, JD KNIGHT, SJL ROBERTS, SH HARLEY, HG WALSH, KV RUNDLE, SA FREYNE, K KOCH, MC EPSTEIN, ND WIERINGA, B SCHONK, D SMEETS, H HADDINGHAM, K SICILIANO, MJ PALMER, DK MILES, JS WOLF, CR FONATSCH, C SHAW, DJ AF BROOK, JD KNIGHT, SJL ROBERTS, SH HARLEY, HG WALSH, KV RUNDLE, SA FREYNE, K KOCH, MC EPSTEIN, ND WIERINGA, B SCHONK, D SMEETS, H HADDINGHAM, K SICILIANO, MJ PALMER, DK MILES, JS WOLF, CR FONATSCH, C SHAW, DJ TI THE PHYSICAL MAP OF CHROMOSOME ARM 19Q - SOME NEW ASSIGNMENTS, CONFIRMATIONS AND REASSESSMENTS SO HUMAN GENETICS LA English DT Article ID MYOTONIC-DYSTROPHY LOCUS; CELL-SURFACE ANTIGENS; RANGE RESTRICTION MAP; TRANSLOCATION BREAKPOINT; MUSCULAR-DYSTROPHY; APOLIPOPROTEIN-CII; GENETIC-MARKERS; DNA-SEQUENCE; LINKAGE; REGION AB We have constructed and analysed somatic cell hybrids from cell lines containing balanced reciprocal translocations involving chromosome 19 and providing two new breakpoints on 19q. These and other hybrids have been tested with a series of markers from 19q to enhance the existing map. Several new cloned DNA sequences that map to 19q13.3-19qter are reported; the locus D19Z1 has been analysed by CHEF gel electrophoresis. C1 NHLBI,CLIN HAEMATOL BRANCH,BETHESDA,MD 20892. UNIV COLL CARDIFF,INST MED GENET,CARDIFF CF4 4XN,S GLAM,WALES. UNIV READING,DEPT MICROBIOL,READING RG1 5AQ,BERKS,ENGLAND. UNIV TEXAS,MD ANDERSON HOSP & TUMOR INST,DEPT GENET,HOUSTON,TX 77030. CATHOLIC UNIV NIJMEGEN,RADBOUD HOSP,DEPT HUMAN GENET,6500 HB NIJMEGEN,NETHERLANDS. ELEANOR ROOSEVELT INST CANC RES,FLORENCE R SABIN LABS,DENVER,CO 80262. UNIV EDINBURGH,DEPT BIOCHEM,IMPERIAL CANC RES FUND,MOLEC PHARMACOL & DRUG METAB LAB,EDINBURGH EH8 9XD,SCOTLAND. HANOVER MED SCH,INST GENET,W-3000 HANNOVER 61,GERMANY. RI Wieringa, Berend/A-5346-2011; OI Wieringa, Berend/0000-0001-9192-8020; Brook, John David/0000-0002-5946-6740 NR 44 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 1991 VL 87 IS 1 BP 65 EP 72 DI 10.1007/BF01213095 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA FN084 UT WOS:A1991FN08400014 PM 2037284 ER PT J AU SVETKEY, LP KADIR, S DUNNICK, NR SMITH, SR DUNHAM, CB LAMBERT, M KLOTMAN, PE AF SVETKEY, LP KADIR, S DUNNICK, NR SMITH, SR DUNHAM, CB LAMBERT, M KLOTMAN, PE TI SIMILAR PREVALENCE OF RENOVASCULAR HYPERTENSION IN SELECTED BLACKS AND WHITES SO HYPERTENSION LA English DT Article DE RENOVASCULAR HYPERTENSION; ETHNIC DIFFERENCES; RENAL ARTERY STENOSIS; PLASMA RENIN ACTIVITY ID CAPTOPRIL TEST; CLINICAL CHARACTERISTICS; RACIAL-DIFFERENCES; RENAL-DISEASE AB Renovascular hypertension is a potentially curable form of high blood pressure that is thought to be extremely rare among blacks. We demonstrate, however, that in a clinically selected population, the prevalence of renovascular hypertension is similar in blacks and whites. We prospectively evaluated 167 hypertensive subjects who had one or more clinical features known to be associated with renovascular hypertension. All subjects had captopril-stimulated peripheral renin measurements and conventional renal arteriography. All significant renal artery stenoses (greater than 50% luminal narrowing) were treated with percutaneous transluminal angioplasty or surgery. Renovascular hypertension was diagnosed if there was a blood pressure response to interventional therapy, according to the criteria established by the Cooperative Study of Renovascular Hypertension. Of the total group evaluated, 24% (39 of 167) had renal artery stenosis and 14% (23 of 167) had renovascular hypertension. Renal artery stenosis or occlusion was found in 27% (26 of 97) of whites and 19% (13 of 67) of blacks (p = 0.27). Renovascular hypertension was diagnosed in 18% (17 of 97) of whites and 9% (6 of 67) of blacks evaluated (p = 0.25). Renovascular hypertension was associated with severe or refractory hypertension and with smoking, but there were no racial differences in these associations. Blacks with renovascular hypertension tended to have low captopril-stimulated peripheral renin activity. We conclude that blacks with clinical features suggestive of renovascular hypertension should be evaluated with angiography. Captopril-stimulated plasma renin may not be useful in detecting blacks with renovascular hypertension, but this and other potential screening tests require further evaluation. C1 NIDR,LDBA,MOLEC MED SECT,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT RADIOL,DURHAM,NC 27710. RP SVETKEY, LP (reprint author), DUKE UNIV,MED CTR,DEPT MED,BOX 3075,DURHAM,NC 27710, USA. FU NCRR NIH HHS [M01-RR-30] NR 21 TC 28 Z9 30 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 1991 VL 17 IS 5 BP 678 EP 683 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FL208 UT WOS:A1991FL20800011 PM 2022411 ER PT J AU MAKINO, M DAVIDSON, WF FREDRICKSON, TN HARTLEY, JW MORSE, HC AF MAKINO, M DAVIDSON, WF FREDRICKSON, TN HARTLEY, JW MORSE, HC TI EFFECTS OF NON-MHC LOCI ON RESISTANCE TO RETROVIRUS-INDUCED IMMUNODEFICIENCY IN MICE SO IMMUNOGENETICS LA English DT Article ID MURINE LEUKEMIA VIRUSES; COLLAGEN-INDUCED ARTHRITIS; HOST-RANGE RESTRICTIONS; MOUSE EMBRYO; CELL-LINES; C57BL/6 MICE; T-CELLS; SUSCEPTIBILITY; INDUCTION; GENES AB Mice of certain strains are highly sensitive to development of a severe immunodeficiency disease following inoculation as adults with LP-BM5 murine leukemia viruses (MuLV) whereas others are extremely resistant. These strain-dependent differences in response to infection have been shown to be genetically determined with resistance to disease being, in general, associated with homozygosity for F-nu-1n and H-2 haplotypes a and d and sensitivity with homozygosity for F-nu-1b and other H-2 haplotypes including b, s, and q. The F-nu-1b, H-2r strain RIIIS/J (RIIIS)was found to be highly resistant to disease even though B 10.RIII(71NS)/J (B10.RIII), also H-2r, was very sensitive, thus excluding a role for H-2 in the resistance of RIIIS. The characteristics of RIIIS resistance were evaluated in studies of infected (B10.RIII x RIIIS) F1, F2 and reciprocal backcross mice. Resistance to disease was shown to be semidominant and determined by more than one gene, although a preponderant influence of a single gene was suggested. Studies of segregating populations showed that resistance was not associated with or linked to polymorphisms of the V-beta complex or genes in proximity to the Emv-2 locus on chromosome 8. However, there was almost complete concordance between absence of disease in infected mice and inhibition of ecotropic virus spread. These results demonstrate that genes other than Fv-1 or H-2 can profoundly influence the development of retrovirus-induced immunodeficiency and replication of ecotropic viruses. C1 NIAID,IMMUNOPATHOL LAB,BLDG 7,ROOM 304,BETHESDA,MD 20892. NCI,GENET LAB,BETHESDA,MD 20892. UNIV CONNECTICUT,DEPT PATHOBIOL,STORRS,CT 06268. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-72622] NR 32 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAY-JUN PY 1991 VL 33 IS 5-6 BP 345 EP 351 DI 10.1007/BF00216693 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA FQ206 UT WOS:A1991FQ20600006 PM 1646765 ER PT J AU WEBER, JS ROSENBERG, SA AF WEBER, JS ROSENBERG, SA TI ADOPTIVE IMMUNOTHERAPY OF CANCER SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID ACTIVATED KILLER CELLS; TUMOR-INFILTRATING LYMPHOCYTES; HUMAN METASTATIC MELANOMAS; HIGH-DOSE INTERLEUKIN-2; ESTABLISHED PULMONARY METASTASES; PERIPHERAL-BLOOD LYMPHOCYTES; PURIFIED HUMAN INTERLEUKIN-2; RECOMBINANT INTERLEUKIN-2; ANTITUMOR-ACTIVITY; AUTOLOGOUS TUMOR RP WEBER, JS (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM B42,BETHESDA,MD 20892, USA. NR 99 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 1991 VL 11 IS 2 BP 381 EP 400 PG 20 WC Allergy; Immunology SC Allergy; Immunology GA FK945 UT WOS:A1991FK94500007 ER PT J AU WICKES, BL GOLIN, JE KWONCHUNG, KJ AF WICKES, BL GOLIN, JE KWONCHUNG, KJ TI CHROMOSOMAL REARRANGEMENT IN CANDIDA-STELLATOIDEA RESULTS IN A POSITIVE EFFECT ON PHENOTYPE SO INFECTION AND IMMUNITY LA English DT Article ID ELECTROPHORETIC KARYOTYPE; DNA-MOLECULES; ALBICANS; YEAST; SEPARATION; PLOIDY AB When type I Candida stellatoidea is plated onto sucrose agar at levels in excess of 10(8) cells, some isolates spontaneously form sucrose-positive colonies. These isolates do not display typical type I phenotypes but instead exhibit phenotypes intermediate between type I C. stellatoidea and C. albicans. Also, this phenotypic change only occurs in conjunction with a chromosomal rearrangement. These rearrangements have been studied in a strain naturally marked for methionine auxotrophy. Chromosome-size DNA bands separated by pulsed-field gel electrophoresis were probed with genes cloned from C. albicans. The hybridization pattern indicated that the genes on several chromosomes underwent extensive rearrangement. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. CATHOLIC UNIV AMER,DEPT BIOL,INST BIOMOLEC STUDIES,WASHINGTON,DC 20064. NR 35 TC 63 Z9 64 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1991 VL 59 IS 5 BP 1762 EP 1771 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA FK377 UT WOS:A1991FK37700026 PM 2019440 ER PT J AU HENDERSON, DK AF HENDERSON, DK TI PRIOR PUBLICATION OF DATA SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Letter ID PRECAUTIONS RP HENDERSON, DK (reprint author), NIH,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAY PY 1991 VL 12 IS 5 BP 274 EP 274 PG 1 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA FR824 UT WOS:A1991FR82400001 ER PT J AU LABROO, VM HEBEL, D KIRK, KL COHEN, LA LEMIEUX, C SCHILLER, PW AF LABROO, VM HEBEL, D KIRK, KL COHEN, LA LEMIEUX, C SCHILLER, PW TI DIRECT ELECTROPHILIC FLUORINATION OF TYROSINE IN DERMORPHIN ANALOGS AND ITS EFFECT ON BIOLOGICAL-ACTIVITY, RECEPTOR AFFINITY AND SELECTIVITY SO INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH LA English DT Article DE ACETYL HYPOFLUORITE; DERMORPHIN ANALOGS; DIRECT ELECTROPHILIC FLUORINATION; FLUORINATED ANALOGS; FLUOROPEPTIDES; OPIOID RECEPTORS; PEPTIDE SEQUENCING; RECEPTOR SELECTIVITY, SOLID PHASE PEPTIDE SYNTHESIS ID DELTA-OPIOID RECEPTORS; MOUSE VAS-DEFERENS; OPIATE RECEPTOR; METHIONINE-ENKEPHALIN; ACETYL HYPOFLUORITE; ELEMENTAL FLUORINE; LEUCINE-ENKEPHALIN; HIGHLY POTENT; AMINO-ACID; PEPTIDES AB In a preliminary communication we reported [(Tetrahedron Lett. 31, 619 (1990)] that acetyl hypofluorite can be used efficiently to introduce fluorine regiospecifically (ortho to OH) into the phenolic ring of tyrosine-containing peptides. This procedure has been applied to the fluorination of a number of mu-selective opioid peptides derived from dermorphin. While the procedure can be used even when the side chains of Arg, Lys, and Tyr are left unprotected, the sulfoxide of a Met(O)-containing analogue was oxidized to sulfone faster than fluorination of the phenolic ring. This method can also be used when the peptide is attached to Merrified resin. Thus, Tyr(3-F)-D-Ala-Phe-Gly-NH2 and Tyr(3-F)-D-Arg-Phe-Lys-NH2 (F-DALDA) have been prepared, purified, and characterized. Affinities of these fluorinated peptides for both mu- and delta-opioid receptors are reduced (two- to nine-fold) relative to their nonfluorinated analogues, but their selectivity for mu-opioid receptors is not significantly altered. Similarly, the in vitro biological potencies (GPI and MVD assays) of the fluorinated analogues are reduced (two- to seven-fold) relative to their nonfluorinated parent peptides. Thus, F-DALDA, which has high affinity (K(i)-mu = 15.2 nM) and selectivity (K(i)-delta/K(i)-mu = 5390) for mu-opioid receptors, has potential use in biochemical studies which utilize F-19 or F-18-labeled compounds. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD. CLIN RES INST MONTREAL,CHEM BIOL & PEPTIDE RES LAB,MONTREAL H2W 1R7,QUEBEC,CANADA. FU NIDA NIH HHS [DA-04443] NR 61 TC 8 Z9 9 U1 1 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0367-8377 J9 INT J PEPT PROT RES JI Int. J. Pept. Protein Res. PD MAY PY 1991 VL 37 IS 5 BP 430 EP 439 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FN063 UT WOS:A1991FN06300009 PM 1680830 ER PT J AU WALTON, LA YADUSKY, A RUBINSTEIN, L AF WALTON, LA YADUSKY, A RUBINSTEIN, L TI INTRAPERITONEAL RADIOACTIVE PHOSPHATE IN EARLY OVARIAN-CARCINOMA - AN ANALYSIS OF COMPLICATIONS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE EARLY OVARIAN CANCER; RADIOACTIVE CHROMIC PHOSPHATE; RADIOACTIVE CHROMIC PHOSPHATE COMPLICATIONS ID STAGE-I; CHROMIC PHOSPHATE; ADJUVANT THERAPY; CANCER; PHOSPHORUS; RADIATION; COLLOIDS; LEUKEMIA; SURGERY; TRIALS AB Intraperitoneal radioactive chromic phosphate was administered to 69 patients with Stage I and II ovarian carcinoma who had undergone comprehensive surgical staging. Intestinal obstruction requiring surgical intervention occurred in four patients and was the most severe complication. Abdominal pain was the most common post-therapy complaint. Attention to time and technique of drug administration could minimize complications. C1 NCI,BIOMET RES BRANCH,ROCKVILLE,MD. RP WALTON, LA (reprint author), UNIV N CAROLINA,SCH MED,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,CB 7570,CHAPEL HILL,NC 27599, USA. NR 32 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY PY 1991 VL 20 IS 5 BP 939 EP 944 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA FL424 UT WOS:A1991FL42400005 PM 2022522 ER PT J AU ELLWEIN, LB LEPKOWSKI, JM THULASIRAJ, RD BRILLIANT, GE AF ELLWEIN, LB LEPKOWSKI, JM THULASIRAJ, RD BRILLIANT, GE TI THE COST-EFFECTIVENESS OF STRATEGIES TO REDUCE BARRIERS TO CATARACT-SURGERY SO INTERNATIONAL OPHTHALMOLOGY LA English DT Article DE COST-EFFECTIVENESS; CATARACT BLINDNESS; VISION SCREENING; HEALTH EDUCATION INTERVENTIONS AB The cost and effectiveness of eight approaches to reducing barriers to cataract surgery were evaluated in a rural area of South India during 1987-1989. The approaches were based on four intervention alternatives - aphakic motivator (AM), basic eye health worker (BW), screening van (SV), and mass media (MM). Each intervention was offered at two levels of economic incentive: partial, which provides free surgery and hospital stay, and full, which also provides transport from the recipient's village to the hospital and free food during the hospital stay. Evaluations took place in a probability selection of 90 villages, including ten control villages not subjected to either of the interventions. Only costs unique to patients from the intervention villages were considered: Health education and screening costs were included, surgery costs were not. Percentage reductions in the cataract blind backlog and increases in surgical coverage were used as effectiveness measures. Analyses suggest that the SV and AM interventions, both with full economic incentive, offer the greatest advantage. The AM intervention is the more effective of the two, but also the more costly. C1 UNIV MICHIGAN,INST SOCIAL RES,ANN ARBOR,MI 48109. ARAVIND EYE HOSP,MADURAI,TAMIL NADU,INDIA. SEVA FON,SAN ANSELMO,CA. NEI,BETHESDA,MD 20892. RP ELLWEIN, LB (reprint author), UNIV NEBRASKA,MED CTR,OMAHA,NE 68105, USA. FU NEI NIH HHS [N0-1-EY-5-2014] NR 6 TC 15 Z9 16 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0165-5701 J9 INT OPHTHALMOL JI Int. Ophthalmol. PD MAY PY 1991 VL 15 IS 3 BP 175 EP 183 DI 10.1007/BF00153924 PG 9 WC Ophthalmology SC Ophthalmology GA FH721 UT WOS:A1991FH72100006 PM 1904845 ER PT J AU DU, DL VOLPE, DA GRIESHABER, CK MURPHY, MJ AF DU, DL VOLPE, DA GRIESHABER, CK MURPHY, MJ TI COMPARATIVE TOXICITY OF FOSTRIECIN, HEPSULFAM AND PYRAZINE DIAZOHYDROXIDE TO HUMAN AND MURINE HEMATOPOIETIC PROGENITOR CELLS-INVITRO SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE FOSTRIECIN; HEPSULFAM; PZDT; HEMATOPOIETIC PROGENITORS; HUMAN; MURINE ID CONDITIONED MEDIUM; COLONY FORMATION; CFU-E; ASSAY; NSC-361456; CLONING; CI-920; LINE AB The in vitro myelotoxic potentials of three investigational antitumor agents, Fostriecin, Hepsulfam and pyrazine diazohydroxide (PZDH), were evaluated utilizing clonogenic assays. Human and murine marrow cells were exposed to each drug for 1 hr prior to culture in microcapillary (human) or Petri dish (murine) assays. Fostriecin (0.22-220-mu-M), Hepsulfam (0.34-340-mu-M) and PZDH (0.68-680-mu-M) inhibited myeloid (CFU-gm) erythroid (BFU-e, CFU-3) and megakaryocytic (CFU-meg) colony formation in a concentration-dependent manner. CFU-e from both species were more sensitive to Fostriecin than the other progenitors and murine cells more sensitive overall to Fostriecin than their human counterparts. Murine CFU-e were also more sensitive to Hepsulfam than human CFU-e, with CFU-gm and BFU-e being similarly affected in both species. Human BFU-e were greatly inhibited by PZDH, whereas murine BFU-e were relatively resistant to its toxic effects. Fostriecin was the most toxic of the three antitum agents, with PZDH the least toxic. C1 HIPPLE CANC RES CTR,4100 S KETTERING BLVD,DAYTON,OH 45439. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [N44-CM-77831] NR 27 TC 16 Z9 16 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 MAY PY 1991 VL 9 IS 2 BP 149 EP 157 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA FK779 UT WOS:A1991FK77900003 PM 1874599 ER PT J AU WIENTJES, MG PLACKE, ME CHANG, MJW PAGE, JG KLUWE, WM TOMASZEWSKI, JE AF WIENTJES, MG PLACKE, ME CHANG, MJW PAGE, JG KLUWE, WM TOMASZEWSKI, JE TI PHARMACOKINETICS OF 2',3'-DIDEOXYADENOSINE IN DOGS SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE 2',3'-DIDEOXYINOSINE; 2',3'-DIDEOXYADENOSINE; PHARMACOKINETICS; DOGS; AIDS; CEREBROSPINAL FLUID ID HTLV-III INFECTIVITY; CELLULAR PHARMACOLOGY; INHIBITOR; INVITRO; 2',3'-DIDEOXYNUCLEOSIDES; ADENINE; CELLS; AIDS AB The pharmacokinetics of 2',3'-dideoxyadenosine (ddAdo) and 2'-3'-dideoxyinosine (ddIno) were determined after intravenous bolus administration and long-term intravenous infusion of ddAdo in dogs. ddAdo was rapidly deaminated to ddIno and ddAdo plasma concentrations were only a fraction of ddIno concentrations. The total body clearance of ddAdo exceeded the literature value for the cardiac output of the dog, indicating an extremely rapid metabolism, and the existence of extrahepatic metabolism. Urinary excretion of unchanged ddAdo was a minor route of elimination (approximately 1%). The pharmacokinetics of ddIno was determined assuming complete conversions of ddAdo to ddIno. ddIno elimination was dose-dependent with total body clearance ranging from 4 to 55 ml/min/kg in individual animals. The plasma half-life was approximately 30 min after most routes of administration but increased to approximately 60 min in two animals receiving a large intravenous dose of 500 mg/kg. ddIno penetrated into the cerebrospinal fluid to a limited extent, reaching concentrations of 3-11% of those in plasma. Urinary excretion of unchanged ddIno accounted for approximately 20% of the administered dose of ddAdo, while uric acid and hypoxanthine were minor urinary metabolites. Concentrations exceeding the in vitro minimal viral inhibitory concentration (2.4-mu-g/mL) could be safely maintained in plasma for a 10-day period. Infusions which gave cerebrospinal fluid concentrations of 12 to 17-mu-g/mL resulted in dose limiting myelosuppression and intestinal toxicity, after less than 10 days of infusion. Orally administered ddAdo was absorbed as ddIno, with bioavailabilities ranging from 28 to 93% in experiments where no emesis occurred. These studies indicate the rapid in vivo conversion of ddAdo to ddIno, and support the selection of ddIno over ddAdo for further drug development. C1 BATTELLE MEM INST,COLUMBUS,OH 43201. NCI,DCT,DTP,TOXICOL BRANCH,BETHESDA,MD 20892. RP WIENTJES, MG (reprint author), OHIO STATE UNIV,DEPT SURG,DIV UROL,COLUMBUS,OH 43210, USA. FU NCI NIH HHS [N01-CM-67869] NR 13 TC 11 Z9 11 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 MAY PY 1991 VL 9 IS 2 BP 159 EP 168 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA FK779 UT WOS:A1991FK77900004 PM 1908444 ER PT J AU DETRICK, B EVANS, CH CHADER, G PERCOPO, CM HOOKS, JJ AF DETRICK, B EVANS, CH CHADER, G PERCOPO, CM HOOKS, JJ TI CYTOKINE-INDUCED MODULATION OF CELLULAR PROTEINS IN RETINOBLASTOMA - ANALYSIS BY FLOW-CYTOMETRY SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; VASCULAR ENDOTHELIAL-CELLS; NECROSIS FACTOR-ALPHA; CLASS-II MOLECULES; HLA-DR; S-ANTIGEN; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODY; INTERFERON-GAMMA; IA ANTIGENS AB Cytokines are a group of specialized, hormone-like proteins that can exert profound influences on cellular development and on a variety of cellular functions. Retinoblastoma cells are an important model for exploring human malignancy and differentiation. These multipotent embryonic cells are capable of differentiating into neuronal, glial-like and retinal pigment epithelium (RPE)-like elements. This report shows that flow cytometric analysis can be used to measure the expression of both cytoplasmic and cell surface proteins in retinoblastoma cells. The authors used this technique to monitor changes in the expression of selected cellular proteins after exposure to specific cytokines and found that MHC class I molecules were augmented by interferon-alpha (IFN-alpha) and interferon-gamma (IFN-gamma), but not by tumor necrosis factor (TNF). However, the MHC class II molecules were augmented by IFN-gamma but not by IFN-alpha or TNF. The neuronal markers, IRBP and PR-6, the glial-like marker, GFAP, and the RPE cell markers, RPE-9 and RPE-15, were not altered by any of the cytokines tested. Furthermore, IFN-gamma induced a striking enhancement of the expression of the photoreceptor cell protein, S-antigen. In contrast, IFN-alpha and TNF did not affect the expression of S-antigen. These studies show that the cytokine, IFN-gamma, can enhance a distinct cellular protein associated with cells committed to a specific cell lineage. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 10,ROOM 6N228,BETHESDA,MD 20892. NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,IMMUNOL & VIROL SECT,IMMUNOL LAB,BETHESDA,MD 20892. NEI,TUMOR BIOL SECT,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 57 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1991 VL 32 IS 6 BP 1714 EP 1722 PG 9 WC Ophthalmology SC Ophthalmology GA FM179 UT WOS:A1991FM17900002 PM 1903363 ER PT J AU ROBBINS, SG DETRICK, B HOOKS, JJ AF ROBBINS, SG DETRICK, B HOOKS, JJ TI OCULAR TROPISMS OF MURINE CORONAVIRUS (STRAIN JHM) AFTER INOCULATION BY VARIOUS ROUTES SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MOUSE HEPATITIS-VIRUS; HERPES-SIMPLEX VIRUS; PLACOID PIGMENT EPITHELIOPATHY; FELINE INFECTIOUS PERITONITIS; DISEASE; MICE; SIALODACRYOADENITIS; NASOENCEPHALOPATHY; ENCEPHALOMYELITIS; PATHOGENESIS AB The coronavirus mouse hepatitis virus (MHV, strain JHM) infects tissues in the anterior and posterior segments when injected intravitreally into adult mouse eyes. Infection causes progressive damage to the photoreceptors and retinal pigment epithelium (RPE), resulting in a disease the authors have termed JHM retinopathy. To determine whether this virus is retinotropic independent of route of inoculation, the authors injected mice with virus by several different routes: into the anterior chamber (AC), onto the cornea, intranasally, or intracerebrally. Inoculation into the AC produced effects similar to those after intravitreal inoculation, although slightly slower in onset. Viral antigen was detected in the anterior portion of the iris on day 3, and by day 6, was also located primarily in the inner nuclear layer, photoreceptors, Muller cells, and RPE. However, by day 10, viral antigens were only detected in a few cells in the ganglion cell layer. Infectious virus was isolated from neural retinas on days 3 and 6, but not on day 10. In contrast, infectious virus could not be isolated from contralateral eyes. After 14 weeks, specific regions of some retinas were atrophied, with most of the retinal layers involved. Inoculation by other routes also resulted in virus-induced disease. Scarification of the cornea with virus, but not application of virus droplets alone, caused pathologic changes in the corneal epithelium and stroma and subtle effects on the ganglion cell and inner plexiform layers. Intracerebral inoculation of virus affected mainly the RPE. Pathologic effects and viral antigens were not detected in eyes from four mice inoculated intranasally. These results show that a murine coronavirus is retinotropic when introduced by several direct routes and one indirect route. Moreover, these studies show that long-lasting retinal disorders ranging in intensity from mild to severe can occur after coronavirus infection. C1 NEI,IMMUNOL & VIROL SECT,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,DIV AIDS,BETHESDA,MD 20892. NR 30 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1991 VL 32 IS 6 BP 1883 EP 1893 PG 11 WC Ophthalmology SC Ophthalmology GA FM179 UT WOS:A1991FM17900023 PM 1851734 ER PT J AU SATO, S TAKAHASHI, Y WYMAN, M KADOR, PF AF SATO, S TAKAHASHI, Y WYMAN, M KADOR, PF TI PROGRESSION OF SUGAR CATARACT IN THE DOG SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ALDOSE REDUCTASE INHIBITORS; GALACTOSE-FED DOGS; PREVENTION; SORBINIL; RATS AB Young beagle dogs were fed a 30% galactose diet, with or without the aldose reductase inhibitors sorbinil or M79175. Cataract formation was monitored by indirect ophtalmoscope and hand-held slit-lamp microscopy and documented by retroillumination photography. In these dogs, the first sign of cataract development was an accentuation of the anterior and posterior lens sutures (1 month after feeding), then the appearance of cortical vacuoles (3 months after feeding), and finally, the formation of predominantly equatorial cortical opacities toward the posterior cortices (4-6 months after feeding). After long-term galactose feeding, a progressive, irregular, clear zone formed at the cortical equatorial regions. Light microscopic examination of these lenses shows that the cataracts are osmotic, many of the lens fibers appear to be swollen or ruptured, and vacuoles are seen near the bow region. Moreover, these histologic changes were reduced in a dose-dependent manner in galactose-fed dogs concomitantly treated with the aldose reductase inhibitors sorbinil or M79175. The osmotic nature of these cataracts and the observation that their formation can be reduced in a dose-dependent manner by aldose reductase inhibitors are consistent with the concept that the aldose-reductase catalyzed formation of polar sugar alcohols (polyols) initiates sugar cataract formation in the dog. C1 OHIO STATE UNIV,COLL VET MED,COLUMBUS,OH 43210. RP SATO, S (reprint author), NEI,BLDG 10,ROOM 10B09,BETHESDA,MD 20892, USA. NR 12 TC 39 Z9 39 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1991 VL 32 IS 6 BP 1925 EP 1931 PG 7 WC Ophthalmology SC Ophthalmology GA FM179 UT WOS:A1991FM17900029 PM 1903366 ER PT J AU RAUB, WF AF RAUB, WF TI COMBINATION THERAPY MOST BENEFICIAL AGAINST RECTAL-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP RAUB, WF (reprint author), NIH,BLDG 31,ROOM 2B23,BETHESDA,MD 20892, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 1 PY 1991 VL 265 IS 17 BP 2173 EP 2173 DI 10.1001/jama.265.17.2173 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FH877 UT WOS:A1991FH87700008 PM 2013940 ER PT J AU RAUB, WF AF RAUB, WF TI TRANSGENIC MICE ALLOW RAPID TESTING OF AGENTS THAT REVERSE MULTIDRUG RESISTANCE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP RAUB, WF (reprint author), NIH,BLDG 31,ROOM 2B23,BETHESDA,MD 20892, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 1 PY 1991 VL 265 IS 17 BP 2173 EP 2173 DI 10.1001/jama.265.17.2173 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FH877 UT WOS:A1991FH87700007 PM 2013940 ER PT J AU RAUB, WF AF RAUB, WF TI LONG-TERM PROPHYLAXIS EFFECTIVE AGAINST RECURRENT URINARY-TRACT INFECTIONS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP RAUB, WF (reprint author), NIH,BLDG 31,ROOM 2B23,BETHESDA,MD 20892, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 1 PY 1991 VL 265 IS 17 BP 2173 EP 2173 DI 10.1001/jama.265.17.2173 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FH877 UT WOS:A1991FH87700006 PM 2013940 ER PT J AU HOFFMAN, WD BANKS, SM ALLING, DW EICHENHOLZ, PW EICHACKER, PQ PARRILLO, JE NATANSON, C AF HOFFMAN, WD BANKS, SM ALLING, DW EICHENHOLZ, PW EICHACKER, PQ PARRILLO, JE NATANSON, C TI FACTORS THAT DETERMINE THE HEMODYNAMIC-RESPONSE TO INHALATION ANESTHETICS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE VOLATILE ANESTHETICS; ENFLURANE; HALOTHANE; ISOFLURANE; LEFT VENTRICULAR EJECTION FRACTION; PHARMACODYNAMICS; DOSE RESPONSE; DOG ID END-EXPIRATORY PRESSURE; LEFT-VENTRICULAR FUNCTION; CARDIOPULMONARY BYPASS; MYOCARDIAL COMPLIANCE; HALOTHANE; ISOFLURANE; DOGS; ENFLURANE AB The hemodynamic response to inhalation anesthesia is influenced by three factors: 1) the specific drug, 2) the dose, and 3) individual characteristics of the subject. To investigate the importance of these factors on the cardiovascular response, we administered five doses [0, 0.5, 1.0, 1.5, and 2.0 minimum alveolar concentration (MAC)] of enflurane, halothane, and isoflurane to each of six dogs. Twelve hemodynamic variables were measured. For all variables, a change in the dose of each drug produced a consistent effect in each dog. Increases in dose resulted in significant decreases in seven variables [left ventricular ejection fraction, cardiac index (CI), stroke volume index (SVI), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), left ventricular stroke work index (LVSWI), and heart rate (HR)] and a significant increase in one variable [central venous pressure (CVP)]. In contrast, the response of individual dogs to different drugs was not consistent. For seven variables [MAP, MPAP, LVSWI, CVP, pulmonary capillary wedge pressure (PCWP), end-diastolic volume index (EDVI), and end-systolic volume index (ESVI)], a significant difference in the responses of a dog to two drugs was greater than zero, whereas a significant difference in the response of at least one other dog to the same two drugs was less than zero (discordant dog-drug interactions). Thus, in contrast to the consistency of the cardiovascular response to changes in dose, the hemodynamic response to different drugs was inconsistent among dogs. We also studied the effect of fluid challenge on hemodynamic response at 1.5 or 2.0 MAC of the three drugs given to each dog. Suppression of volume-induced increase in HR and CI was found at 1.5 and 2.0 MAC of enflurane, but only at 2.0 MAC for the other two drugs. The anesthetics produced a markedly decreased response for SVI, EDVI, ESVI, MAP, CI, HR, and LVSWI but an increased response for MPAP, PCWP, and CVP compared with responses in awake dogs. C1 ARMED FORCES RADIOBIOL RES INST,DEF NUCL AGCY,BETHESDA,MD 20814. RP HOFFMAN, WD (reprint author), NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 23 TC 11 Z9 11 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 MAY PY 1991 VL 70 IS 5 BP 2155 EP 2163 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA FL024 UT WOS:A1991FL02400036 PM 1864798 ER PT J AU SHAH, S PETERKOFSKY, A AF SHAH, S PETERKOFSKY, A TI CHARACTERIZATION AND GENERATION OF ESCHERICHIA-COLI ADENYLATE-CYCLASE DELETION MUTANTS SO JOURNAL OF BACTERIOLOGY LA English DT Note ID GENE-PRODUCTS; DNA; MUTATIONS; CLONING; VECTOR AB Escherichia coli DELTA-cya-283 is a 75-bp in-frame deletion overlapping the 5' end of DELTA-cya-854; DELTA-cya-201 is a 41-bp frameshift deletion overlapping the 3' end of DELTA-cya-854. Sequence repeats were found at the boundaries of DELTA-cya-283 and DELTA-cya-201, suggesting a mechanism for deletion formation. Recombinant DNA procedures were used to construct a strain in which the total cya structural gene in the chromosome was replaced by the kanamycin resistance gene. C1 NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NR 19 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1991 VL 173 IS 10 BP 3238 EP 3242 PG 5 WC Microbiology SC Microbiology GA FL181 UT WOS:A1991FL18100028 PM 2022622 ER PT J AU REDDI, AH CUNNINGHAM, NS AF REDDI, AH CUNNINGHAM, NS TI RECENT PROGRESS IN BONE INDUCTION BY OSTEOGENIN AND BONE MORPHOGENETIC PROTEINS - CHALLENGES FOR BIOMECHANICAL AND TISSUE ENGINEERING SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article; Proceedings Paper CT SYMP OF TISSUE ENGINEERING CY APR 06-12, 1990 CL KEYSTONE, CO SP UNIV CALIF LOS ANGELES ID EXTRACELLULAR-MATRIX; DIFFERENTIATION; BETA AB Implantation of demineralized bone matrix results in local bone induction. Bone induction is a sequential biological chain reaction that consists of chemotaxis and proliferation of mesenchymal cells and differentiation of bone. Osteogenin, a bone morphogenetic protein has been purified and the amino acid sequence determined. Recently a family of bone morphogenetic proteins have been cloned and expressed by recombinant DNA technology. The availability of growth and morphogenetic factors will permit the rational design of new bone. The challenge for the biomechanical engineer is to attain mechanically optimal and functionally adaptive new bone for various skeletal prostheses. We are on the threshold for fabrication of new bone based on sound architectural design principles of tissue engineering based on cellular and molecular biology of growth and differentiation factors. C1 NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. NR 15 TC 22 Z9 23 U1 1 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD MAY PY 1991 VL 113 IS 2 BP 189 EP 190 DI 10.1115/1.2891233 PG 2 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA HP749 UT WOS:A1991HP74900011 PM 1875692 ER PT J AU VETTER, U FISHER, LW MINTZ, KP KOPP, JB TUROSS, N TERMINE, JD ROBEY, PG AF VETTER, U FISHER, LW MINTZ, KP KOPP, JB TUROSS, N TERMINE, JD ROBEY, PG TI OSTEOGENESIS IMPERFECTA - CHANGES IN NONCOLLAGENOUS PROTEINS IN BONE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID SMALL PROTEOGLYCAN-I; OSTEONECTIN; COLLAGEN; BIGLYCAN; TISSUES; DECORIN; FORM AB The noncollagenous proteins osteonectin, bone sialoprotein, osteocalcin, the small proteoglycan decorin (PG II), and alpha-2-HS glycoprotein (which is synthesized in the liver but highly concentrated in bone) were measured in extracts of cortical bone from 3 type I, 2 type II, 8 type III and 13 type IV patients with osteogenesis imperfecta (OI) and from 7 control subjects. Osteonectin was found to be reduced in the bone of all OI patients. The bone from severely affected type III OI patients contained the lowest levels of osteonectin. In contrast, bone sialoprotein was found to be elevated in the bones of OI patients. The highest levels were found in individuals classified as type IV patients. Osteocalcin and alpha-2-HS glycoprotein concentrations were increased in all OI patients. Decorin levels were not significantly altered in OI bones compared to controls. These changes in the concentrations of the noncollagenous proteins may contribute to the fragility of the OI bone by interfering with complete mineralization and/or normal tissue architecture. RP VETTER, U (reprint author), NIDR,BONE RES BRANCH,BLDG 30,RM 106,BETHESDA,MD 20892, USA. RI Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Kopp, Jeffrey/0000-0001-9052-186X NR 28 TC 50 Z9 50 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 1991 VL 6 IS 5 BP 501 EP 505 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GZ109 UT WOS:A1991GZ10900011 PM 2068957 ER PT J AU LAURIE, SM ROBBINS, AR AF LAURIE, SM ROBBINS, AR TI A TOXIN-RESISTANT MOUSE L-CELL MUTANT DEFECTIVE IN PROTEIN-TRANSPORT ALONG THE SECRETORY PATHWAY SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HAMSTER OVARY CELLS; RECEPTOR-MEDIATED ENDOCYTOSIS; VESICULAR STOMATITIS-VIRUS; DIPHTHERIA-TOXIN; EUKARYOTIC RIBOSOMES; POLYACRYLAMIDE GELS; INTERNALIZED RICIN; PSEUDOMONAS TOXIN; FUSION PROTEIN; FILM DETECTION AB Using methods designed for isolation of mutants defective in receptor-mediated endocytosis, a novel L-cell mutant was obtained that exhibits resistance to three different protein toxins as well as alterations in secretion. This mutant, LEFIC, is resistant to modeccin, Pseudomonas exotoxin, and ricin. These toxins, which enter the cytoplasm via receptor-mediated endocytosis, are thought to penetrate into cells at the level of late endosomes or the trans Golgi network. Early endosomal acidification appears to be normal in the mutant based on its accumulation of iron from transferrin and its sensitivity to diphtheria toxin A chain-transferrin conjugate. Within the secretory pathway two delays in transport of vesicular stomatitis virus (VSV) G protein were observed in LEFIC: a 20-30 min delay in acquisition of Endo H resistance and a 1-2 hr delay in appearance of newly synthesized G protein on the cell surface. Movement of endogenous proteins along the secretory pathway was also affected in LEFIC. Fibronectin secretion was delayed by 15 min, and membrane proteins were delayed in arrival at the cell surface. The phenotype of LEFIC is consistent with a defect in a component or compartment shared by both the late endocytic and constitutive secretory pathways. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 52 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1991 VL 147 IS 2 BP 215 EP 223 DI 10.1002/jcp.1041470205 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA FQ592 UT WOS:A1991FQ59200004 PM 1645740 ER PT J AU BISGAARD, HC THORGEIRSSON, SS AF BISGAARD, HC THORGEIRSSON, SS TI EVIDENCE FOR A COMMON CELL OF ORIGIN FOR PRIMITIVE EPITHELIAL-CELLS ISOLATED FROM RAT-LIVER AND PANCREAS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GLUTATHIONE-S-TRANSFERASES; OVAL CELLS; POLYCHLORINATED-BIPHENYLS; MONOCLONAL-ANTIBODIES; DIFFERENTIATION; HEPATOCYTES; EXPRESSION; HEPATOCARCINOGENESIS; CYTOKERATINS; POPULATIONS AB The appearance of differentiated hepatocytes in the adult rat pancreas as well as pancreatic-type tissue in the adult rat liver can be experimentally induced (Reddy et al.: J. Cell Biol., 98:2082-2090, 1984; Rao et al., J. Histochem. Cytochem., 34:197-201, 1986). These observations suggest a lineage relationship between cell compartments present in rat liver and pancreas. The present data demonstrate that epithelial cell lines with almost identical phenotypes can be established from adult rat liver and pancreas. The established cell lines showed similar morphologies as established by light- and electron-microscopic studies. The cell lines showed a unique expression pattern of intermediate filament proteins. Vimentin, actin, and beta-tubulin were present in all cell lines. In addition, simple epithelial type II cytokeratins 7 and 8 were found to be coexpressed with the type I cytokeratin 14 in several of the cell lines. Neither the type I cytokeratins 18 and 19, which are the normal partners for cytokeratins 8 and 7 in filament formation, nor the type II cytokeratin 5 could be detected despite the fact that filaments were formed by both cytokeratins 8 and 14. This suggests that cytokeratin 14 acts as an indiscriminate type I cytokeratin in filament formation in the established cell lines. The cell lines expressed the same sets of LDH and aldolase isoenzymes and identical sets of glutathione transferase subunits. In addition, the epithelial cell lines from liver and pancreas were equally sensitive to the growth-inhibitory effects of TGF-beta-1. No expression of tissue- or cell-specific proteins such as alpha-fetoprotein, albumin, amylase, elastase, or gamma-glutamyl transpeptidase were detected. The almost identical phenotypes of the hepatic and pancreatic cell lines suggest that they may be derived from a common primitive epithelial cell type present in both rat liver and pancreas. In contrast to parenchymal cells, these cells have an extended capacity for proliferation in vitro and may represent a progeny from a "precursor" or "stem" cell compartment in vivo. C1 NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892. NR 52 TC 67 Z9 69 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1991 VL 147 IS 2 BP 333 EP 343 DI 10.1002/jcp.1041470220 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA FQ592 UT WOS:A1991FQ59200019 PM 1710229 ER PT J AU SPEIR, E SASSE, J SHRIVASTAV, S CASSCELLS, W AF SPEIR, E SASSE, J SHRIVASTAV, S CASSCELLS, W TI CULTURE-INDUCED INCREASE IN ACIDIC AND BASIC FIBROBLAST GROWTH-FACTOR ACTIVITIES AND THEIR ASSOCIATION WITH THE NUCLEI OF VASCULAR ENDOTHELIAL AND SMOOTH-MUSCLE CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX; MESSENGER-RNA; CARDIAC MYOCYTES; FACTOR RECEPTOR; FACTOR-I; EXPRESSION; PROTEIN; SERUM; IDENTIFICATION; SEQUENCE AB The activity of acidic and basic fibroblast growth factor-like mitogens (aFGF, bFGF) extracted from cultured bovine aortic endothelial (BAEC) and rat aortic smooth muscle cells (SMC) was compared with that of freshly isolated cells from the same tissues. Extracts of subendothelial extracellular matrix (ECM) and cell lysates of cultured BAEC contained 4-fold more bFGF-like activity than the extracts of fresh cells. ECM and cell lysates of SMC yielded 10-fold more bFGF-like activity than the fresh cell lysates. We consistently find aFGF-like activity in both cell types. In the case of BAEC, cultured cells and ECM contained 3-fold more aFGF-like activity when compared with freshly isolated cells, whereas in cultured SMC, aFGF-like activity in cell and ECM extracts was 8-fold higher than in fresh cell extracts. The mitogens extracted from cell lysates and from the ECM are closely related to aFGF or bFGF by the criteria that they bind to heparin-sepharose and elute at 1.1 M (aFGF) or 1.5 M (bFGF) NaCl, have molecular weights of about 18,000, and react with anti-aFGF (1.1 M), or anti-bFGF (1.5M) antibodies when analyzed by Western blots and by radioimmunoassay specific for aFGF and bFGF. This mitogenic activity is inhibited by neutralizing antibodies to aFGF and bFGF. In addition, the column fractions are potent mitogens for Balb/c 3T3 fibroblasts. Acidic and basic FGF-like mitogenic activity could also be extracted from the cell nuclei. The subcellular localization of both FGFs was visualized in both nuclei and cytoplasm with immunoperoxidase. Compared with primary SMC, secondary SMC had an increased capacity to bind 125IaFGF to high affinity receptors, while binding to freshly isolated BAEC and SMC was negligible. We conclude that FGFs are present at low levels in freshly isolated cells and that propagation in cell culture provides a stimulus for production of these mitogens. C1 SHRINERS HOSP CRIPPLED CHILDREN,TAMPA,FL 33612. RP SPEIR, E (reprint author), NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892, USA. NR 42 TC 58 Z9 59 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1991 VL 147 IS 2 BP 362 EP 373 DI 10.1002/jcp.1041470223 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA FQ592 UT WOS:A1991FQ59200022 PM 1710230 ER PT J AU MILNE, GWA WILLETT, P AF MILNE, GWA WILLETT, P TI A TRIBUTE TO LYNCH,MICHAEL,F. SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Item About an Individual C1 UNIV SHEFFIELD,SHEFFIELD S10 2TN,S YORKSHIRE,ENGLAND. RP MILNE, GWA (reprint author), NIH,MED CHEM LAB,BLDG 37,ROOM 5C28,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD MAY PY 1991 VL 31 IS 2 BP 175 EP 175 DI 10.1021/ci00002a001 PG 1 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA FN009 UT WOS:A1991FN00900001 ER PT J AU WHALEY, R HODES, L AF WHALEY, R HODES, L TI CLUSTERING A LARGE NUMBER OF COMPOUNDS .2. USING THE CONNECTION MACHINE SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article AB About 230 000 compounds in the National Cancer Institute Repository are available for screening under a new protocol. This paper is the second on an project to extract a representative sample of these compounds by clustering. The clustering program was implemented on the Connection Machine, a massively parallel computer with 16K processing elements. This implementation reduced a formidable task to a relatively routine run. C1 NCI,BETHESDA,MD 20892. THINKING MACHINES CORP,CAMBRIDGE,MA 02142. NR 5 TC 12 Z9 12 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD MAY PY 1991 VL 31 IS 2 BP 345 EP 347 DI 10.1021/ci00002a022 PG 3 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA FN009 UT WOS:A1991FN00900023 PM 1874824 ER PT J AU HODES, L FELDMAN, A AF HODES, L FELDMAN, A TI CLUSTERING A LARGE NUMBER OF COMPOUNDS .3. THE LIMITS OF CLASSIFICATION SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article AB Clustering is normally used to group items that are similar. In this application of obtaining a diverse sample from the 230 000 compounds in the National Cancer Institute Repository, we cluster to select compounds that are different from the rest, to optimize screening for new leads. With these constraints, our approach yielded many singleton clusters. We can interpret these results as evidence for a limit to classification, contrary to the customary view of chemistry as a study of classes of compounds. RP HODES, L (reprint author), NCI,BETHESDA,MD 20892, USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD MAY PY 1991 VL 31 IS 2 BP 347 EP 350 DI 10.1021/ci00002a023 PG 4 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA FN009 UT WOS:A1991FN00900024 PM 1874825 ER PT J AU ZHOU, HX ZWANZIG, R AF ZHOU, HX ZWANZIG, R TI A RATE-PROCESS WITH AN ENTROPY BARRIER SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID DYNAMICS; DIFFUSION; LANGEVIN AB This paper presents a simple dynamical model of a rate process in which the rate appears to be controlled by an entropy barrier, rather than an energy barrier. The model consists of independent particles moving in a two-dimensional region bounded by four reflecting disks. The particles collide elastically with the walls. A bottleneck separates the region into reactants and products. The extent of the reaction is followed by using computer simulations to get the time dependence of the number correlation function of reactants. The particle dynamics are either frictionless (inertial), moderately frictional (Langevin dynamics), or strongly frictional (Brownian dynamics). For small bottlenecks, the number correlation function generally decays in time as a single exponential. The transition rate in the frictionless limit is predicted correctly by microcanonical transition state theory. As the strength of the friction is increased, the rate changes to the diffusive limit without the usual Kramers turnover. RP ZHOU, HX (reprint author), NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Zhou, Huan-Xiang/M-5170-2016 OI Zhou, Huan-Xiang/0000-0001-9020-0302 NR 14 TC 75 Z9 76 U1 1 U2 13 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAY 1 PY 1991 VL 94 IS 9 BP 6147 EP 6152 DI 10.1063/1.460427 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA FH765 UT WOS:A1991FH76500043 ER PT J AU ACOSTA, CK BAHR, ML BURDETT, JE CESSAC, JW MARTINEZ, RA RAO, PN KIM, HK AF ACOSTA, CK BAHR, ML BURDETT, JE CESSAC, JW MARTINEZ, RA RAO, PN KIM, HK TI SYNTHESIS OF UNNATURAL AMINO-ACIDS SO JOURNAL OF CHEMICAL RESEARCH-S LA English DT Article C1 NICHHD,CONTRACEPTIVE DEV BRANCH,BETHESDA,MD 20892. SW FDN BIOMED RES,DEPT ORGAN CHEM,POB 28147,SAN ANTONIO,TX 78228. NR 14 TC 5 Z9 5 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0308-2342 J9 J CHEM RES-S JI J. Chem. Res.-S PD MAY PY 1991 IS 5 BP 110 EP 111 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA FN468 UT WOS:A1991FN46800002 ER PT J AU GRADY, CL HAXBY, JV HORWITZ, B SCHAPIRO, MB SALERNO, J GONZALEZ, A RAPOPORT, SI AF GRADY, CL HAXBY, JV HORWITZ, B SCHAPIRO, MB SALERNO, J GONZALEZ, A RAPOPORT, SI TI ACTIVATION OF FRONTAL-CORTEX DURING FACE PERCEPTION IN ALZHEIMER-TYPE DEMENTIA (DAT) SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD MAY PY 1991 VL 13 IS 3 BP 419 EP 419 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA FP351 UT WOS:A1991FP35100033 ER PT J AU AZARI, NP SCHAPIRO, MB RAPOPORT, SI HORWITZ, B AF AZARI, NP SCHAPIRO, MB RAPOPORT, SI HORWITZ, B TI GENDER DIFFERENCES IN CORRELATIONS OF REGIONAL CEREBRAL GLUCOSE METABOLIC RATES (RCMRGLC) OBTAINED BY POSITRON EMISSION TOMOGRAPHY (PET) SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD MAY PY 1991 VL 13 IS 3 BP 441 EP 441 PG 1 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA FP351 UT WOS:A1991FP35100127 ER PT J AU HANNAH, JS VERDERY, RB BODKIN, NL HANSEN, BC LE, NA HOWARD, BV AF HANNAH, JS VERDERY, RB BODKIN, NL HANSEN, BC LE, NA HOWARD, BV TI CHANGES IN LIPOPROTEIN CONCENTRATIONS DURING THE DEVELOPMENT OF NONINSULIN-DEPENDENT DIABETES-MELLITUS IN OBESE RHESUS-MONKEYS (MACACA-MULATTA) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HIGH-DENSITY LIPOPROTEIN; CORONARY HEART-DISEASE; ENDOGENOUS HYPERTRIGLYCERIDEMIA; INSULIN ACTION; TRIGLYCERIDE; CHOLESTEROL; METABOLISM; MEN AB Abnormalities in plasma lipoprotein concentrations commonly found in subjects with noninsulin-dependent diabetes may be related to insulin resistance, hyperinsulinemia, hyperglycemia, or other metabolic defects. The middle-aged obese rhesus monkey is an animal model in which these defects can be separated in time during the development of diabetes. It is, therefore, a model system for examining the sequence of metabolic changes which occur before and after the onset of diabetes. This sequence of changes was used in the present study to determine if lipoprotein changes occur in association with the development of diabetes in the rhesus monkey. Increases in plasma triglyceride, very low density lipoprotein (VLDL) triglyceride, and VLDL cholesterol, and decreases in high density lipoprotein cholesterol were observed across previously identified groups ranging from normal to diabetic. Plasma triglycerides increased from 0.54 +/- 0.09 (normal) to 1.27 +/- 0.50, 1.93 +/- 0.79, and 4.28 +/- 2.24 in three intermediate groups with progressive hyperinsulinemia and insulin resistance, to 7.59 +/- 2.73 mmol/L in the diabetic monkeys. Increases in VLDL triglyceride increases. High density lipoprotein cholesterol decreased across the groups from 2.33 +/- 0.16 (normal) to 1.72 +/- 0.20, 1.17 +/- 0.13, and 1.09 +/- 0.20 mmol/L in the intermediate groups, and was lowest in the diabetic monkeys, 1.00 +/- 0.21. The obese rhesus monkey can therefore be used to study lipoprotein abnormalities as they occur both before and in noninsulin-dependent diabetes. C1 UNIV MARYLAND, SCH MED, DEPT PHYSIOL, BALTIMORE, MD 21201 USA. NIA, DIV METAB, BALTIMORE, MD 21224 USA. RP HANNAH, JS (reprint author), MEDLANT RES FDN, GEORGE HYMAN MEM RES BLDG, 108 IRVING ST NW, WASHINGTON, DC 20010 USA. RI Hansen, Barbara/J-8723-2012 OI Hansen, Barbara/0000-0001-9646-3525 FU NIDDK NIH HHS [DK-37717] NR 42 TC 28 Z9 29 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 MAY PY 1991 VL 72 IS 5 BP 1067 EP 1072 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FH996 UT WOS:A1991FH99600019 PM 2022707 ER PT J AU IDA, H KURATA, A EGUCHI, K KAWAKAMI, A MIGITA, K FUKUDA, T NAKAMURA, T KUSUMOTO, Y BERZOFSKY, JA NAGATAKI, S AF IDA, H KURATA, A EGUCHI, K KAWAKAMI, A MIGITA, K FUKUDA, T NAKAMURA, T KUSUMOTO, Y BERZOFSKY, JA NAGATAKI, S TI DIFFERENT B-CELL RESPONSES TO HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) ENVELOPE SYNTHETIC PEPTIDES IN HTLV-I-INFECTED INDIVIDUALS SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-I); HUMAN ANTI-HTLV-I-ENV ANTIBODIES; SYNTHETIC PEPTIDES; IMMUNODOMINANT SITES ID TROPICAL SPASTIC PARAPARESIS; HUMAN IMMUNODEFICIENCY VIRUS; LEUKEMIA-LYMPHOMA; ANTIGENIC SITES; ANTIBODIES; PROTEIN; RETROVIRUS; MYELOPATHY; PATIENT AB HTLV-I (human T-cell lymphotropic virus type I) is the retrovirus related to two distinct diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-I-associated myelopathy (HAM). We analyzed the difference in antibody activities against the viral protein and the difference in specificities of anti-HTLV-I envelope antibodies among HTLV-I-infected individuals from the same HTLV-I-endemic area using a HTLV-I-gag-env hybrid protein and HTLV-I-env-encoded synthetic peptides as antigens, respectively. The difference in the responses of IgG anti-HTLV-I envelope antibody production among HTLV-I-infected individuals was qualitative as well as quantitative. Sera from patients with HAM showed significantly higher activities of antibodies against HTLV-I-gag-env hybrid protein than sera from other HTLV-I-infected individuals including ATLL patients. The specificities of IgG anti-HTLV-I-envelope antibodies, tested on seven synthetic envelope peptides, were directed mainly against four sites, V1E7 (residues 97-111), V1E8 (191-209), and V1E9 (268-286) on gp46 and V1E1 (342-363) on gp21. Three of these sites were shown to be immunodominant T-cell sites in mice in our previous study. Whereas patients in all categories made antibodies specific for V1E1 and V1E8, only HAM patients made antibodies to the V1E7 and V1E9 epitopes, suggesting a qualitative difference in response. Whether this difference is of pathogenetic significance is not clear. The antibody activities and the specificities against the envelope protein were also analyzed in nine HTLV-I-infected polyarthritis patients because a clinical entity of specific arthritis related to HTLV-I infection has been suggested; the activities of anti-HTLV-I antibodies in sera from HTLV-I-infected polyarthritis patients were not different from the activities of the antibodies from normal HTLV-I-carriers, and no envelope peptide-specificity unique for the arthritis patients was detected. C1 NAGASAKI UNIV,SCH MED,DEPT INTERNAL MED 1,NAGASAKI 852,JAPAN. NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. OI nagataki, shigenobu/0000-0002-9974-3554 NR 25 TC 9 Z9 9 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 1991 VL 11 IS 3 BP 143 EP 151 DI 10.1007/BF00918682 PG 9 WC Immunology SC Immunology GA FP236 UT WOS:A1991FP23600004 PM 1890164 ER PT J AU SAMUNI, A WINKELSBERG, D PINSON, A HAHN, SM MITCHELL, JB RUSSO, A AF SAMUNI, A WINKELSBERG, D PINSON, A HAHN, SM MITCHELL, JB RUSSO, A TI NITROXIDE STABLE RADICALS PROTECT BEATING CARDIOMYOCYTES AGAINST OXIDATIVE DAMAGE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE RAT HEART CELLS; SUPEROXIDE RADICAL; NITROXIDE SPIN-LABELS ID SUPEROXIDE-DISMUTASE; REPERFUSION INJURY; HYDROGEN-PEROXIDE; DEFEROXAMINE; ENHANCEMENT; GENERATION; MYOCARDIUM; METABOLISM; MECHANISM; TISSUES AB The protective effect of stable nitroxide radicals against oxidative damage was studied using cardiomyocyte cultures obtained from newborn rats. Monolayered cardiomyocytes were exposed to H2O2 and the effect on spontaneous beating and leakage of LDH was determined. Hydrogen peroxide irreversibly blocked rhythmic beating and resulted in a significant membrane injury as shown by release of LDH. The injury was prevented by catalase which removes H2O2 and by cell-permeable, metal-chelating agents such as desferrioxamine or bipyridine. In contrast, reagents which are excluded from the cell such as superoxide dismutase or DTPA did not protect the cells against H2O2. Five- and six-membered ring, stable nitroxide radicals which have previously been shown to chemically act as low-molecular weight, membrane-permeable, SOD-mimetic compounds provided full protection. The nitroxides prevented leakage of LDH and preserved normal cardiomyocyte contractility, presumably by intercepting intracellular O2- radicals. Alternatively, protection may result through nitroxides reacting with reduced transition metal ions or by detoxifying secondary organic radicals. C1 NCI,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3 B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SCH MED,DEPT MOLEC BIOL,IL-91010 JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,SCH MED,DEPT BIOCHEM,IL-91010 JERUSALEM,ISRAEL. NR 29 TC 138 Z9 140 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1991 VL 87 IS 5 BP 1526 EP 1530 DI 10.1172/JCI115163 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FK453 UT WOS:A1991FK45300007 PM 1850756 ER PT J AU BOUMPAS, DT ANASTASSIOU, ED OLDER, SA TSOKOS, GC NELSON, DL BALOW, JE AF BOUMPAS, DT ANASTASSIOU, ED OLDER, SA TSOKOS, GC NELSON, DL BALOW, JE TI DEXAMETHASONE INHIBITS HUMAN INTERLEUKIN-2 BUT NOT INTERLEUKIN-2 RECEPTOR GENE-EXPRESSION INVITRO AT THE LEVEL OF NUCLEAR TRANSCRIPTION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CORTICOSTEROIDS; GENE REGULATION; GLUCOCORTICOSTEROIDS; MESSENGER RNA; MESSENGER RNA STABILITY ID CELL GROWTH-FACTOR; HUMAN LYMPHOCYTES-T; MESSENGER-RNA; CYCLOSPORIN-A; ACTIVATION; MYC; PROLIFERATION; MECHANISMS; INDUCTION; PROMOTER AB Glucocorticosteroids have an inhibitory effect on the expression of interleukin 2 (IL-2) and interleukin 2 receptor (IL-2R) genes. To determine the mechanisms of this inhibition, human T lymphocytes were stimulated with mitogens in the presence of dexamethasone. Nuclear transcription run-off assays showed that high doses of dexamethasone inhibited the transcription of the IL-2 gene but not that of the IL-2R gene. Post-transcriptionally, high doses of dexamethasone (10(-4) M) were required to inhibit IL-2R mRNA levels by 50%, whereas lower doses (10(-6) M) inhibited by > 70% the accumulation of IL-2 mRNA. IL-2 mRNA half-life decreased in the presence of dexamethasone (10(-6) M) by approximately 50%. At the protein product level, dexamethasone inhibited both IL-2 production, as well as cell surface and soluble forms of IL-2R. IL-2R gene expression was inhibited for at least 72 h after exposure of cells to dexamethasone. In the presence of exogenous IL-2, dexamethasone failed to exert a significant effect on the production of IL-2R protein. These data indicate that dexamethasone has a greater effect on the expression of the IL-2 gene than on the IL-2R gene. Dexamethasone both inhibits transcription of the IL-2 gene and decreases the stability of IL-2 mRNA. The effect of dexamethasone on the IL-2R gene is post-transcriptional and may result indirectly from decreased IL-2 production. C1 NCI,IMMUNOBIOL SECT,BETHESDA,MD 20892. RP BOUMPAS, DT (reprint author), NIDDKD,KIDNEY DIS SECT,BLDG 10,ROOM 3N-116,BETHESDA,MD 20892, USA. NR 41 TC 110 Z9 111 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1991 VL 87 IS 5 BP 1739 EP 1747 DI 10.1172/JCI115192 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FK453 UT WOS:A1991FK45300036 PM 2022743 ER PT J AU ALLEN, JB WONG, HL GUYRE, PM SIMON, GL WAHL, SM AF ALLEN, JB WONG, HL GUYRE, PM SIMON, GL WAHL, SM TI ASSOCIATION OF CIRCULATING RECEPTOR FC-GAMMA-RIII-POSITIVE MONOCYTES IN AIDS PATIENTS WITH ELEVATED LEVELS OF TRANSFORMING GROWTH-FACTOR-BETA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CD16, CD32, CD64; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE SUPPRESSION; MATURATION; MONONUCLEAR PHAGOCYTES ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MONONUCLEAR PHAGOCYTE SYSTEM; PERIPHERAL-BLOOD MONOCYTES; NATURAL-KILLER CELLS; MONOCLONAL-ANTIBODIES; HUMAN-LYMPHOCYTES; HUMAN MACROPHAGES; IGG; INFECTION; EXPRESSION AB Monocytes in the circulation of normal individuals express two receptors for the constant region of immunoglobulin, Fc-gamma-RI and Fc-gamma-RII. In contrast, we have observed that AIDS monocytes express significant levels of a third Fc-gamma-R, Fc-gamma-RIII (CD16), which is normally associated with activation or maturation of the monocyte population. By dual-fluorescence analysis using a monoclonal antibody specific for Fc-gamma-RIII (MAb 3G8), 38.5 +/- 3.2% of the LeuM3 (CD14)-positive monocytes in AIDS patients were CD16 positive as compared to 10.4 +/- 1.0% for healthy individuals (n = 29; P < 0.005). Furthermore, AIDS monocytes expressed Fc-gamma-RIII-specific mRNA which is expressed minimally or not at all in control monocytes. As a recently identified inducer of Fc-gamma-RIII expression on blood monocytes, transforming growth factor-beta (TGF-beta) was found to be elevated in the serum and/or plasma of AIDS patients. Moreover, incubation of normal monocytes with AIDS serum or plasma induced CD16 expression which correlated with serum TGF-beta levels (r = 0.74, P < 0.001) and was inhibited with a neutralizing antibody to TGF-beta. Thus, the increased CD16 expression on peripheral blood monocytes in AIDS patients may be the consequence of elevated circulating levels of the polypeptide hormone TGF-beta. C1 NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BLDG 30,ROOM 326,BETHESDA,MD 20892. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,HANOVER,NH 03756. GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20037. NR 54 TC 134 Z9 135 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1991 VL 87 IS 5 BP 1773 EP 1779 DI 10.1172/JCI115196 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FK453 UT WOS:A1991FK45300040 PM 1708784 ER PT J AU LEE, CM CHANG, PP TSAI, SC ADAMIK, R PRICE, SR KUNZ, BC MOSS, J TWIDDY, EM HOLMES, RK AF LEE, CM CHANG, PP TSAI, SC ADAMIK, R PRICE, SR KUNZ, BC MOSS, J TWIDDY, EM HOLMES, RK TI ACTIVATION OF ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXINS BY NATIVE AND RECOMBINANT ADENOSINE-DIPHOSPHATE RIBOSYLATION FACTORS, 20-KD GUANINE-NUCLEOTIDE BINDING-PROTEINS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ADENOSINE DIPHOSPHATE RIBOSYLATION FACTOR; CHOLERA TOXIN; ENTEROTOXINS; QUANINE NUCLEOTIDE BINDING PROTEINS ID ADP-RIBOSYLTRANSFERASE ACTIVITY; AMINO-ACID-SEQUENCE; CHOLERA-TOXIN; VIBRIO-CHOLERAE; ADENYLATE-CYCLASE; REGULATORY COMPONENT; GUANYL NUCLEOTIDES; GENE; PURIFICATION; RECEPTOR AB Escherichia coli heat-labile enterotoxins (LT) are responsible in part for "traveler's diarrhea" and related diarrheal illnesses. The family of LTs comprises two serogroups termed LT-1 and LT-II; each serogroup includes two or more antigenic variants. The effects of LTs result from ADP ribosylation of G(s-alpha), a stimulatory component of adenylyl cyclase; the mechanism of action is identical to that of cholera toxin (CT). The ADP-ribosyl-transferase activity of CT is enhanced by 20-kD guanine nucleotide-binding proteins, known as ADP-ribosylation factors or ARFs. These proteins directly activate the CTA1 catalytic unit and stimulate its ADP ribosylation of G(s-alpha), other proteins, and simple guanidino compounds (e.g., agmatine). Because of the similarities between CT and LTs, we investigated the effects of purified bovine brain ARF and a recombinant form of bovine ARF synthesized in Escherichia coli on LT activity. ARF enhanced the LT-I-, LT-IIa-, and LT-IIb-catalyzed ADP ribosylation of agmatine, as well as the auto-ADP ribosylation of the toxin catalytic unit. Stimulation of ADP-ribosylagmatine formation by LTs and CT in the presence of ARF was GTP dependent and enhanced by sodium dodecyl sulfate. With agmatine as substrate, LT-IIa and LT-IIb exhibited < 1% the activity of CT and LT-Ih. CT and LTs catalyzed ADP-ribosyl-G(s-alpha) formation in a reaction dependent on ARF, GTP, and dimyristoyl phosphatidylcholine/cholate. With G(s-alpha) as substrate, the ADP-ribosyltransferase activities of the toxins were similar, although CT and LT-Ih appeared to be slightly more active than LT-IIa and LT-IIb. Thus, LT-IIa and LT-IIb appear to differ somewhat from CT and LT-Ih in substrate specificity. Responsiveness to stimulation by ARF, GTP, and phospholipid/detergent as well as the specificity of ADP-ribosyltransferase activity are functions of LTs from serogroups LT-I and LT-II that are shared with CT. C1 NHLBI,CELLULAR METAB LAB,MOLEC MECHANISMS SECT,BLDG 10,ROOM 5N307,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,BETHESDA,MD 20814. OI LEE, CHII-MING/0000-0002-1075-5787 FU NIAID NIH HHS [AI-14107] NR 51 TC 40 Z9 40 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1991 VL 87 IS 5 BP 1780 EP 1786 DI 10.1172/JCI115197 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FK453 UT WOS:A1991FK45300041 PM 1902492 ER PT J AU PARKINSON, DR AF PARKINSON, DR TI LEVAMISOLE AS ADJUVANT THERAPY FOR MELANOMA - QUO-VADIS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MALIGNANT-MELANOMA; PLACEBO; TRIAL RP PARKINSON, DR (reprint author), NCI,BETHESDA,MD 20892, USA. NR 6 TC 12 Z9 12 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 MAY PY 1991 VL 9 IS 5 BP 716 EP 717 PG 2 WC Oncology SC Oncology GA FJ833 UT WOS:A1991FJ83300002 PM 2016613 ER PT J AU SMITH, MA AF SMITH, MA TI THE IMPACT OF DOXORUBICIN DOSE INTENSITY ON SURVIVAL OF PATIENTS WITH EWINGS-SARCOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID ADVANCED BREAST; TOXICITY; CANCER RP SMITH, MA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 10 TC 7 Z9 7 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 MAY PY 1991 VL 9 IS 5 BP 889 EP 890 PG 2 WC Oncology SC Oncology GA FJ833 UT WOS:A1991FJ83300030 PM 2016632 ER PT J AU JACOBSEN, FM AF JACOBSEN, FM TI POSSIBLE AUGMENTATION OF ANTIDEPRESSANT RESPONSE BY BUSPIRONE SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEPRESSION; FLUOXETINE; DISORDER; TRIAL AB In open trials, seven of eight antidepressant nonresponders reported partial or full antidepressant response after the addition of buspirone 10 mg t.i.d. An additional eight of nine patients who suffered winter relapses of depression while receiving previously effective antidepressant regimens showed remission of depressive symptoms after the addition of buspirone 10 mg t.i.d. Improvement after the addition of buspirone was maintained for at least 3 months, and side effects were minimal in most patients. These results suggest that low doses of buspirone may be useful in augmenting antidepressant response. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP JACOBSEN, FM (reprint author), TRANSCULTURAL MENTAL HLTH INST,1301 20TH ST,NW SUITE 711,WASHINGTON,DC 20036, USA. NR 16 TC 86 Z9 90 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 1991 VL 52 IS 5 BP 217 EP 220 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA FP686 UT WOS:A1991FP68600004 PM 2033029 ER PT J AU SUMMERS, RG MUSIAL, CE CHENG, PC LEITH, A MARKO, M AF SUMMERS, RG MUSIAL, CE CHENG, PC LEITH, A MARKO, M TI THE USE OF CONFOCAL MICROSCOPY AND STERECON RECONSTRUCTIONS IN THE ANALYSIS OF SEA-URCHIN EMBRYONIC-CELL DIVISION SO JOURNAL OF ELECTRON MICROSCOPY TECHNIQUE LA English DT Article DE SEA URCHIN DEVELOPMENT; IMAGE RECONSTRUCTION; COMPUTER GRAPHICS ID HEMICENTROTUS-PULCHERRIMUS AB A laser scanning confocal microscope has been used to investigate the development of the sea urchin embryo. The samples were fixed in Carnoy's solution at various developmental stages, stained for DNA with the Feulgen reaction, and optically sectioned with a BioRad MRC-500 confocal microscope. Computer-generated stereographic projection images and a three-dimensional contour tracing and reconstruction system were employed to investigate the cleavage pattern during the 6th cleavage division. Cell division is found to be asynchronous during the 6th cleavage, with macromere derivatives completing division first, followed by mesomeres, and finally by the outer quartet of micromeres (which begins division only after macromeres and mesomeres have completed their respective divisions). Sixth cleavage produces an embryo comprising 60 cells. Asynchronous division was also observed within individual tiers of blastomeres. Variations in the orientations of cell division axes within individual tiers of cells were also observed. The utility of computer-graphics reconstruction techniques for both quantitative and qualitative developmental analysis are discussed. C1 SUNY BUFFALO,SCH ENGN & APPL SCI,DEPT ELECT & COMP ENGN,ADV MICROSCOPY & IMAGING LAB,BUFFALO,NY 14260. NIH BIOL MICROSCOPY & IMAGE RECONSTRUCT RESOURCE,WADSWORTH CTR LABS & RES,ALBANY,NY 12201. RP SUMMERS, RG (reprint author), SUNY BUFFALO,SCH MED & BIOMED SCI,DEPT ANAT SCI,BUFFALO,NY 14214, USA. FU NCRR NIH HHS [P41 RR001219]; PHS HHS [R01219] NR 19 TC 15 Z9 15 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 0741-0581 J9 J ELECTRON MICR TECH PD MAY PY 1991 VL 18 IS 1 BP 24 EP 30 DI 10.1002/jemt.1060180105 PG 7 WC Biology; Microscopy SC Life Sciences & Biomedicine - Other Topics; Microscopy GA FG802 UT WOS:A1991FG80200004 PM 2056349 ER PT J AU SMITH, GJ BAGNELL, CR BAKEWELL, WE BLACK, KA BOULDIN, TW EARNHARDT, TS HOOK, GER PRYZWANSKY, KB AF SMITH, GJ BAGNELL, CR BAKEWELL, WE BLACK, KA BOULDIN, TW EARNHARDT, TS HOOK, GER PRYZWANSKY, KB TI APPLICATION OF CONFOCAL SCANNING LASER MICROSCOPY IN EXPERIMENTAL PATHOLOGY SO JOURNAL OF ELECTRON MICROSCOPY TECHNIQUE LA English DT Article DE APOPTOSIS; SURFACTANT APOPROTEIN-A; BLOOD-NERVE BARRIER; PINOCYTOSIS ID PULMONARY SURFACTANT; CELL-DEATH; FLOW-CYTOMETRY; OXYGEN-TENSION; GLYCOPROTEIN-A; BLOOD-FLOW; RAT; FLUORESCENCE; MACROPHAGES; NEUROPATHY AB Confocal scanning laser microscopy (CSLM) represents an exciting new tool for scientific disciplines which focus on mechanistic studies such as experimental pathology. Enhanced resolution in the specimen plane and rejection of out-of-focus fluorescence flare allow analysis of specific nucleic acid sequences, enzymes, structural macromolecules, and cellular homeostasis utilizing fluorescent probes. Four different experimental applications are discussed which utilize CSLM to evaluate pathological processes at the subcellular, cellular, and tissue levels. Programmed cell death, or apoptosis, is a natural process of significance both during development and as a response to toxic stimuli. CSLM-imaging of nuclei of human B lymphoblastoid cells following exposure to a monofunctional alkylating agent suggests that the degradation of chromatin characteristic of apoptosis may occur in asymmetric patterns. Surfactant apoprotein-A is the major non-serum protein component of pulmonary surfactant and is essential for the extracellular function of surfactant. CSLM of alveolar type II cells suggests that apoprotein-A is present in both the cytoplasm, predominantly in lamellar bodies, and in the nucleus. The tumor promoter, phorbol myristate acetate, rapidly stimulated the formation of vacuoles in human neutrophils. CSLM using Lucifer Yellow as a probe suggests that cylindrical vacuoles are formed by fluid-phase pinocytosis. The blood-nerve barrier (BNB) in peripheral nerves may be an important target during toxin-induced neuropathies. Ricin-induced permeability of the BNB in the rat was rapidly visualized by CSLM as leakage of fluorescein isothiocynate (FITC)-dextran into the endoneurial compartment. C1 UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC 27709. RP SMITH, GJ (reprint author), UNIV N CAROLINA,DEPT PATHOL,CB 7525,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [CA-24144, CA-42765]; NIEHS NIH HHS [ES-07126] NR 44 TC 28 Z9 30 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0741-0581 J9 J ELECTRON MICR TECH PD MAY PY 1991 VL 18 IS 1 BP 38 EP 49 DI 10.1002/jemt.1060180107 PG 12 WC Biology; Microscopy SC Life Sciences & Biomedicine - Other Topics; Microscopy GA FG802 UT WOS:A1991FG80200006 PM 2056350 ER PT J AU LADLEY, RW CAMPBELL, AD HICKS, ML LI, SH AF LADLEY, RW CAMPBELL, AD HICKS, ML LI, SH TI EFFECTIVENESS OF HALOTHANE USED WITH ULTRASONIC OR HAND INSTRUMENTATION TO REMOVE GUTTA-PERCHA FROM THE ROOT-CANAL SO JOURNAL OF ENDODONTICS LA English DT Article ID ENDODONTIC RETREATMENT; REINSTRUMENTATION AB This study compared halothane and chloroform used with hand or ultrasonic instrumentation to remove gutta-percha and sealer from root canals. Apically extruded debris, residual debris, time for filling removal, and amount of solvent used were determined. The differences in extruded apical debris and radiographically visible residual debris were not significant (p > 0.05). Ultrasonic instrumentation required significantly less time to remove the root canal filling than did hand instrumentation (p = 0.02). The only significant difference in the amount of solvent used occurred when the ultrasonic-chloroform group was compared with the hand instrumentation-chloroform group (p = 0.05). Halothane was found to be an acceptable alternative to chloroform for removing gutta-percha and sealer from the obturated root canal. C1 USN,NAVAL DENT SCH,NATL NAVAL DENT CTR,BETHESDA,MD 20889. USN,DEPT ENDODONT,DENT CLIN,NAVAL STN,MAYPORT,FL. FMFPAC,FSSG 1ST,DENT BN 1ST,DENT CO 13TH,EL TORO,CA. NATL INST DENTAL RES,BIOMETRY SECT,BETHESDA,MD. NR 12 TC 25 Z9 27 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0099-2399 J9 J ENDODONT JI J. Endod. PD MAY PY 1991 VL 17 IS 5 BP 221 EP 224 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA FK200 UT WOS:A1991FK20000004 PM 1940742 ER PT J AU NETA, R OPPENHEIM, JJ SCHREIBER, RD CHIZZONITE, R LEDNEY, GD MACVITTIE, TJ AF NETA, R OPPENHEIM, JJ SCHREIBER, RD CHIZZONITE, R LEDNEY, GD MACVITTIE, TJ TI ROLE OF CYTOKINES (INTERLEUKIN-1, TUMOR-NECROSIS-FACTOR, AND TRANSFORMING GROWTH-FACTOR-BETA) IN NATURAL AND LIPOPOLYSACCHARIDE-ENHANCED RADIORESISTANCE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; FACTOR-ALPHA; PROLIFERATION; MACROPHAGES; RADIATION; RECEPTORS AB Studies of radioresistance and radioprotection provide an excellent in vivo model for dissection of the pathophysiological role of cytokines. The availability of neutralizing antibodies to cytokines has made it possible to assess the contribution of cytokines to host defense and repair processes involved in radioresistance and radioprotection. Administration of anti-interleukin 1 receptor (IL-1R) antibody (35F5) or anti-tumor necrosis factor (TNF) antibody (TN3 19.12) reduced survival of irradiated CD2F1 mice. These results demonstrate conclusively that natural levels of IL-1 and TNF contribute to radioresistance of normal mice. Furthermore, the radioprotective effect of administered IL-1 was blocked not only with anti-IL-1R antibody but also with anti-TNF antibody. Similarly, the radioprotective effect of TNF was reduced with anti-IL-1R antibody. These data suggest that cooperative interaction of both cytokines is necessary to achieve successful radioprotection. Finally, when LPS was used as a radioprotector, the combined administration of anti-IL-1R and anti-TNF not only blocked the radioprotection with LPS, but actually revealed LPS to have a radiosensitizing effect. This effect may be due to induction of TGF-beta, since administration of this cytokine results in reduced survival of irradiated mice. C1 NCI,BIOL RESPONSE MODIFIER PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21701. WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. HOFFMANN LA ROCHE INC,ROCHE RES CTR,DEPT MOLEC GENET,NUTLEY,NJ 07110. RP NETA, R (reprint author), ARMED FORCES RADIOBIOL RES INST,DEPT EXPTL HEMATOL,BETHESDA,MD 20814, USA. RI Schreiber, Robert/A-1276-2013 OI Schreiber, Robert/0000-0001-6311-0432 NR 36 TC 123 Z9 125 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1991 VL 173 IS 5 BP 1177 EP 1182 DI 10.1084/jem.173.5.1177 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA FH752 UT WOS:A1991FH75200016 PM 2022925 ER PT J AU SKEEL, A YOSHIMURA, T SHOWALTER, SD TANAKA, S APPELLA, E LEONARD, EJ AF SKEEL, A YOSHIMURA, T SHOWALTER, SD TANAKA, S APPELLA, E LEONARD, EJ TI MACROPHAGE STIMULATING PROTEIN - PURIFICATION, PARTIAL AMINO-ACID-SEQUENCE, AND CELLULAR-ACTIVITY SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CULTURED HUMAN-MONOCYTES; PERITONEAL-MACROPHAGES; MEDIATED PHAGOCYTOSIS; COMPLEMENT RECEPTOR; ACTIVATION; FIBRONECTIN; INVITRO; SERUM AB Macrophage stimulating protein (MSP) was purified to homogeneity from human blood plasma by selection of biologically active fractions obtained by sequential immunoaffinity and high pressure liquid ion exchange chromatography. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis the molecular mass of MSP was 70 kilodaltons (kD); under reducing conditions two gel bands were seen, at 47 and 22 kD. The disulfide-linked two-chain structure of MSP was confirmed by separation of reduced and alkylated MSP chains. A computer search comparison of six partial sequences of MSP digests showed that MSP has not been recorded in data banks of protein sequences. Two MSP fragments had > 80% identity in overlaps of 12-16 residues to sequences in the protein family that includes human prothrombin, plasminogen, and hepatocyte growth factor. The concentration of purified MSP required for half-maximal biological activity was the order of 10(-10) M. In addition to making mouse resident peritoneal macrophages responsive to chemo-attractants, MSP caused the appearance of long cytoplasmic processes and pinocytic vesicles in freshly plated macrophages. MSP also caused phagocytosis via the C3b receptor, CR1. Whereas resident peritoneal macrophages bind but do not ingest sheep erythrocytes opsonized with IgM anti-Forssman antibody and mouse C3b, addition of MSP caused ingestion. Thus, MSP causes direct or indirect activation of two receptors of the mouse resident peritoneal macrophage, CR1 and the C5a receptor. C1 NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,BLDG 560,RM 12-71,FREDERICK,MD 21702. NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,CELL BIOL LAB,CHEM SECT,BETHESDA,MD 20892. NR 26 TC 155 Z9 159 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1991 VL 173 IS 5 BP 1227 EP 1234 DI 10.1084/jem.173.5.1227 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA FH752 UT WOS:A1991FH75200021 PM 1827141 ER PT J AU DOI, T STRIKER, LJ KIMATA, K PETEN, EP YAMADA, Y STRIKER, GE AF DOI, T STRIKER, LJ KIMATA, K PETEN, EP YAMADA, Y STRIKER, GE TI GLOMERULOSCLEROSIS IN MICE TRANSGENIC FOR GROWTH-HORMONE - INCREASED MESANGIAL EXTRACELLULAR-MATRIX IS CORRELATED WITH KIDNEY MESSENGER-RNA LEVELS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID HEPARAN-SULFATE PROTEOGLYCAN; BASEMENT-MEMBRANE; COLLAGEN; IDENTIFICATION; LAMININ; TISSUES; CHAIN; IV AB Mice transgenic for growth hormone (GH) develop progressive glomerulosclerosis. The compositions of kidney extracellular matrix (ECM) and ECM mRNA were examined. The glomerulosclerotic areas in GH mice contained types I and IV collagen, laminin, and basement membrane heparan sulfate proteoglycan (HSPG), which increased with age. The type IV collagen, laminin B2, and HSPG mRNA levels in GH mice, measured by a solution hybridization RNase protection assay, were increased over normal littermates. These findings suggest that the accumulation of ECM components in the glomeruli of GH mice is regulated at the transcriptional level and that glomerulosclerosis is, in part, due to the excess production of ECM rather than simply a reduction in its turnover. The glomerular lesions in GH mice resemble diabetic nephropathy and may allow further dissection of the molecular basis of certain forms of glomerulosclerosis. C1 NIDR,DEV BIOL & ANOMALLES LAB,BETHESDA,MD 20892. AICHI MED UNIV,INST MOLEC SCI MED,NAGAKUTE,AICHI 48011,JAPAN. RP DOI, T (reprint author), NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,BLDG 10,ROOM 3N110,BETHESDA,MD 20892, USA. NR 18 TC 103 Z9 105 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1991 VL 173 IS 5 BP 1287 EP 1290 DI 10.1084/jem.173.5.1287 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA FH752 UT WOS:A1991FH75200027 PM 2022927 ER PT J AU HERSHFIELD, B INOUYE, L CHADER, G RIPPS, H AGUIRRE, G AF HERSHFIELD, B INOUYE, L CHADER, G RIPPS, H AGUIRRE, G TI ORGANIZATION AND TRANSCRIPTION OF CANINE (CAC)N SEQUENCES SO JOURNAL OF HEREDITY LA English DT Note ID DNA FINGERPRINTS; MINISATELLITE; VERTEBRATE; GENOMES; PROBES; RNA C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV ILLINOIS,COLL MED,DEPT OPHTHALMOL,LIONS ILLINOIS EYE RES INST,CHICAGO,IL 60680. RP HERSHFIELD, B (reprint author), UNIV PENN,SCH VET MED,MED GENET SECT,3850 SPRUCE ST,PHILADELPHIA,PA 19104, USA. FU NEI NIH HHS [EY06516, EY06855, EY01244] NR 12 TC 8 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0022-1503 J9 J HERED JI J. Hered. PD MAY-JUN PY 1991 VL 82 IS 3 BP 251 EP 254 PG 4 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA FV436 UT WOS:A1991FV43600015 PM 2061597 ER PT J AU CHANG, K DING, I KERN, FG WILLINGHAM, MC AF CHANG, K DING, I KERN, FG WILLINGHAM, MC TI MOLECULAR GENETIC AND IMMUNOCHEMICAL ANALYSIS OF MUTANT P53 IN HUMAN OVARIAN-CANCER SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Meeting Abstract C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 1991 VL 39 IS 5 BP 728 EP 728 PG 1 WC Cell Biology SC Cell Biology GA FH027 UT WOS:A1991FH02700065 ER PT J AU CHANG, K PASTAN, I WILLINGHAM, MC AF CHANG, K PASTAN, I WILLINGHAM, MC TI ISOLATION OF A MONOCLONAL-ANTIBODY, K1, THAT REACTS WITH OVARIAN CANCERS AND MESOTHELIUM SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Meeting Abstract C1 NCI,MOLEC BIOL LAB,ULTRASTRUCT CYTOCHEM SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAY PY 1991 VL 39 IS 5 BP 728 EP 728 PG 1 WC Cell Biology SC Cell Biology GA FH027 UT WOS:A1991FH02700064 ER PT J AU GOLDSTEIN, DS GROSSMAN, E TAMRAT, M CHANG, PC EISENHOFER, G BACHER, J KIRK, KL BACHARACH, S KOPIN, IJ AF GOLDSTEIN, DS GROSSMAN, E TAMRAT, M CHANG, PC EISENHOFER, G BACHER, J KIRK, KL BACHARACH, S KOPIN, IJ TI POSITRON EMISSION IMAGING OF CARDIAC SYMPATHETIC INNERVATION AND FUNCTION USING F-18 6-FLUORODOPAMINE - EFFECTS OF CHEMICAL SYMPATHECTOMY BY 6-HYDROXYDOPAMINE SO JOURNAL OF HYPERTENSION LA English DT Article DE CATECHOLAMINES F-DOPAMINE; SYMPATHETIC NERVOUS SYSTEM; 6-HYDROXYDOPAMINE; POSITRON EMISSION TOMOGRAPHY; FLUORODOPAMINE ID NEURONAL UPTAKE; NEUROTRANSMITTERS; 2-FLUORODOPAMINE; 6-FLUORODOPAMINE; FATE; RATS AB Hypotheses concerning the pathophysiology of hypertension, cardiac failure and other cardiovascular disorders have imputed abnormal cardiac sympathoneural activity. Here we describe a technique to examine cardiac sympathetic innervation and function using positron emission tomographic (PET) scanning after systemic intravenous injection of F-18-6-fluorodopamine, and the effects of chemical sympathectomy by the neurotoxin, 6-hydroxydopamine (6-OHDA). Uptake of F-18-6-fluorodopamine by the heart of anesthetized dogs resulted in striking delineation of the left ventricular myocardium. Myocardial radioactivity declined bi-exponentially, with a half-life of approximately 2 h during the longer phase. In 6-OHDA-treated animals, the ventricular myocardium was barely distinguishable from the chamber; myocardial radioactivity declined rapidly and was virtually absent within 30 min after injection of F-18-6-fluorodopamine. The rates of decline in myocardial radioactivity in dogs treated with 6-OHDA were similar to those in dogs treated with reserpine, but the mechanisms of sympatholysis by these drugs were distinguished by arterial plasma levels of 6-fluorodihydroxyphenylacetic acid (6-FDOPAC). Plasma 6-FDOPAC levels were diminished in 6-OHDA-treated dogs and elevated in reserpinized dogs. The results confirm that, after injection of F-18-6-fluorodopamine, cardiac sympathetic nerve endings are radiolabeled, allowing visualization of sites of sympathetic innervation. Combined assessments of PET time-activity curves and plasma levels of metabolites of F-18-6-fluorodopamine constitute a new, potentially clinically applicable means by which to examine cardiac sympathetic function. C1 NIH,CTR CLIN,DEPT NUCL MED,PET SECT,BETHESDA,MD 20892. NIDDKD,CHEM LAB,PHOENIX,AZ. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. BAKER MED RES INST,PRAHRAN,VIC 3181,AUSTRALIA. NIH,DIV RES SERV,VET RESOURCES BRANCH,BETHESDA,MD 20892. RP GOLDSTEIN, DS (reprint author), NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N214,BETHESDA,MD 20892, USA. NR 13 TC 28 Z9 28 U1 0 U2 1 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 MAY PY 1991 VL 9 IS 5 BP 417 EP 423 DI 10.1097/00004872-199105000-00005 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FM174 UT WOS:A1991FM17400005 PM 1649861 ER PT J AU HACKETT, CJ YEWDELL, JW BENNINK, JR WYSOCKA, M AF HACKETT, CJ YEWDELL, JW BENNINK, JR WYSOCKA, M TI CLASS-II MHC-RESTRICTED T-CELL DETERMINANTS PROCESSED FROM EITHER ENDOSOMES OR THE CYTOSOL SHOW SIMILAR REQUIREMENTS FOR HOST PROTEIN-TRANSPORT BUT DIFFERENT KINETICS OF PRESENTATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; RAPID COLORIMETRIC ASSAY; ANTIGEN-PRESENTING CELLS; INFLUENZA-VIRUS; ENDOGENOUS ANTIGEN; HEMAGGLUTININ MOLECULE; BREFELDIN-A; RECOGNITION; LINES; NEURAMINIDASE AB We have studied the role of APC protein transport in presentation of class II MHC-restricted T cell determinants of influenza virus glycoproteins that have distinct Ag processing requirements. Two I-E(d)-restricted epitopes were analyzed: hemagglutinin (HA) 111-119, which is processed by the exogenous/endocytic pathway, and neuraminidase (NA) 79-93, which has a requirement for cytosolic processing. NA 79-93 is presented from infectious but not nonreplicative virus under ordinary conditions. This requirement for viral biosynthesis could be bypassed by using a soluble inhibitor of NA,2,3-dehydro-2-deoxy-N-acetyl neuraminic acid (DDAN), to facilitate cytosolic introduction of virus. APC exposed to UV virus/DDAN present HA and NA determinants derived directly from proteins of the input virus particles. This allows presentation of both endocytically and cytosolically processed epitopes in the same experiment using noninfectious virus. The inhibitor brefeldin A (BFA) was used to interrupt host protein transport at various times relative to virus/DDAN addition. We observed that BFA added simultaneously with virus blocked recognition of NA 79-93 but not HA 111-119. This distinction was found to be based upon different expression kinetics of the HA and NA determinants. Expression of NA 79-93 required 6 to 9 h, whereas HA 111-119 was presented by 1 h after Ag addition. When APC were incubated with BFA at intervals before virus addition, presentation of HA 111-119 was also blocked as a function of time. Data indicate that about 5 h of BFA treatment is needed to deplete host protein pools required for presentation of I-E(d)-restricted T cell determinants processed from either endosomes or the cytosol. C1 NIAID,VIRAL DIS LAB,ROCKVILLE,MD 20852. RP HACKETT, CJ (reprint author), WISTAR INST,3601 SPRUCE ST,PHILADELPHIA,PA 19104, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; OI Hackett, Charles/0000-0003-4586-9669 FU NIAID NIH HHS [AI 14162, AI 22961] NR 55 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1991 VL 146 IS 9 BP 2944 EP 2951 PG 8 WC Immunology SC Immunology GA FJ133 UT WOS:A1991FJ13300008 PM 1673146 ER PT J AU KOTAKE, S DESMET, MD WIGGERT, B REDMOND, TM CHADER, GJ GERY, I AF KOTAKE, S DESMET, MD WIGGERT, B REDMOND, TM CHADER, GJ GERY, I TI ANALYSIS OF THE PIVOTAL RESIDUES OF THE IMMUNODOMINANT AND HIGHLY UVEITOGENIC DETERMINANT OF INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; T-CELL EPITOPES; IRBP; IDENTIFICATION; RECOGNITION; PINEALITIS; ACTIVATION; ANTIGEN; RATS; ENCEPHALOMYELITIS AB Interphotoreceptor retinoid-binding protein (IRBP), a retinal-specific Ag, induces experimental autoimmune uveitis in a variety of animals. We have previously shown that sequence 1169-1191 of bovine IRBP is the immunodominant epitope of this protein in Lewis rats and is highly immunogenic and uveitogenic in these rats. The active site of peptide 1169-1191 was determined by testing its truncated forms. The shortest peptide to be immunologically active was found to be 1182-1190 (WEGVGVVPD). To determine the role of individual residues of this sequence, we have tested the immunologic activities of nine analogs of peptide 1181-1191, in which each of residues 1182-1190 was substituted with alanine (A). The tested activities included the capacity to induce experimental autoimmune uveitis and cellular responses in immunized rats, as well as the capability to stimulate lymphocytes sensitized against IRBP or the parent peptide 1181-1191. Analogs that did not stimulate these lymphocytes were also tested for their capacity to competitively inhibit the proliferative response to 1181-1191. Analogs A(1184), A(1186), and A(1187) resembled 1181-1191 in their activities, whereas the other analogs exhibited remarkably reduced activities, with several patterns being noticed. Analog A(1182) was inactive in all tests. Analog A(1190) was very weakly uveitogenic and non-immunogenic, but it stimulated lymphocytes sensitized against IRBP or 1181-1191 when added at exceedingly high concentrations. Analogs A(1183) and A(1185) resembled A(1190) in being weakly uveitogenic and A(1185) was also found to be poorly immunogenic. In addition, relatively high concentrations of A(1183) and A(1185) were needed to stimulate lymphocytes sensitized against IRBP or 1181-1191. However, a different pattern of activities was exhibited by analogs A(1188) and A(1189). These peptides were uveitogenic and immunogenic, but failed to stimulate lymphocytes sensitized to IRBP or 1181-1191. Furthermore, A(1188) and A(1189), but not A(1182), also inhibited the response to 1181-1191 of a cell line specific toward this parent peptide. The data are interpreted to show that residues 1188 and 1189 are involved in the interaction of the peptide with the TCR, whereas residues 1182 and 1190 and, perhaps, 1183 and 1185, are pivotal for the binding of peptide 1181-1190 to the MHC molecules on APC. C1 NEI,IMMUNOL LAB,BLDG 10,RM 10N208,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. OI Redmond, T. Michael/0000-0002-1813-5291; de Smet, Marc/0000-0002-9217-5603 NR 34 TC 25 Z9 26 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1991 VL 146 IS 9 BP 2995 EP 3001 PG 7 WC Immunology SC Immunology GA FJ133 UT WOS:A1991FJ13300016 PM 1707928 ER PT J AU KRIEG, AM GOURLEY, MF STEINBERG, AD AF KRIEG, AM GOURLEY, MF STEINBERG, AD TI ASSOCIATION OF MURINE LUPUS AND THYMIC FULL-LENGTH ENDOGENOUS RETROVIRAL EXPRESSION MAPS TO A BONE-MARROW STEM-CELL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKEMOGENIC RETROVIRUSES; MICE; VIRUS; TRANSPLANTATION; EPITHELIUM; STRAINS AB Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymic epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells. C1 NIAMS,ARB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. NR 18 TC 19 Z9 19 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 MAY 1 PY 1991 VL 146 IS 9 BP 3002 EP 3005 PG 4 WC Immunology SC Immunology GA FJ133 UT WOS:A1991FJ13300017 PM 2016535 ER PT J AU DRESKIN, SC METZGER, H AF DRESKIN, SC METZGER, H TI FC-EPSILON-RI-MEDIATED HYDROLYSIS OF PHOSPHOINOSITIDES IN GHOSTS DERIVED FROM RAT BASOPHILIC LEUKEMIA-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAST-CELLS; PHOSPHOLIPASE-C; RBL-2H3 CELLS; INOSITOL 1,4,5-TRISPHOSPHATE; IMMUNOGLOBULIN-E; PLASMA-MEMBRANE; BINDING PROTEIN; IGE RECEPTORS; PHOSPHATIDYLINOSITOL; ACTIVATION AB Aggregation of the high affinity receptor for IgE (Fc-epsilon-RI) on mast cells by a polyvalent Ag leads to hydrolysis of phosphoinositides (PI) catalyzed by phospholipase C (PI-PLC). To understand this phenomenon in molecular terms, it is important to obtain active, cell-free preparations. In extensive preliminary studies, we could not demonstrate Fc-epsilon-RI-mediated activation of PI-PLC in plasma membranes prepared by conventional methods from rat basophilic leukemia cells. We now report a stepwise approach involving preparation of cytoplasts from such cells and then hypotonic lysis of the cytoplasts to obtain active membrane vesicles. These membranes, best described as "ghosts," appear to reseal after losing greater than 90% of their soluble, cytoplasmic components and contain receptors that when aggregated, activate PI-PLC to hydrolyze endogenous phospholipids. Per unit of plasma membrane, the ghosts retain approximately 25% of Fc-epsilon-RI-mediated stimulation of PI-PLC relative to the cells. This activity requires ATP, magnesium, phosphoenolpyruvate, and, to a limited degree, calcium. Although an adequate amount of phosphatidylinositol biphosphate is present, the predicted spike of (1,4,5)-inositol trisphosphate is not seen, and the predominant inositol phosphate isomer is (1,4)-inositol bisphosphate. This is the first report of Fc-epsilon-RI-mediated activation of PI-PLC in a cytoplasm-depleted system that demonstrates activation of endogenous enzyme acting on endogenous substrate. In addition, it is the first such report for any receptor of the Ig superfamily. C1 NIAMSD,BETHESDA,MD. RP DRESKIN, SC (reprint author), UNIV COLORADO,HLTH SCI CTR,DIV CLIN IMMUNOL,BOX B164,4200 E 9TH AVE,DENVER,CO 80262, USA. FU DRS NIH HHS [BRSG-05357] NR 44 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1991 VL 146 IS 9 BP 3102 EP 3109 PG 8 WC Immunology SC Immunology GA FJ133 UT WOS:A1991FJ13300033 PM 1849942 ER PT J AU ASHER, AL MULE, JJ KASID, A RESTIFO, NP SALO, JC REICHERT, CM JAFFE, G FENDLY, B KRIEGLER, M ROSENBERG, SA AF ASHER, AL MULE, JJ KASID, A RESTIFO, NP SALO, JC REICHERT, CM JAFFE, G FENDLY, B KRIEGLER, M ROSENBERG, SA TI MURINE TUMOR-CELLS TRANSDUCED WITH THE GENE FOR TUMOR-NECROSIS-FACTOR-ALPHA - EVIDENCE FOR PARACRINE IMMUNE EFFECTS OF TUMOR-NECROSIS-FACTOR AGAINST TUMORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HETEROTRANSPLANTED HUMAN-TUMORS; PROMOTE MARROW ENGRAFTMENT; TISSUE GRAFT TOLERANCE; MONOCLONAL-ANTIBODIES; FACTOR TNF; PULMONARY METASTASES; INTERFERON-GAMMA; CYTO-TOXICITY; FACTOR-BETA; INVIVO AB Studies of the anti-tumor activity of TNF-alpha in vivo have been hampered by the need to administer systemically toxic doses of the cytokine to obtain a curative response. To facilitate studies of the effect of high local concentrations of TNF-alpha on tumor growth and host immunity, a newly induced murine sarcoma was transduced with the gene for human TNF-alpha and the biologic characteristics of these cells were examined. We identified high and low TNF-producing tumor clones which exhibited stable TNF secretion over time. Significant amounts of membrane associated TNF were found in a high-TNF producing clone as well. No difference in the in vitro growth rates between TNF-producing and nonproducing cell lines was observed. In contrast, in vivo studies demonstrate that although unmodified parental tumor cells grew progressively when implanted s.c. in animals, tumor cells transduced with the TNF gene were found to regress in a significant number of animals after an initial phase of growth. This effect correlated with the amount of TNF produced and could be blocked with a specific anti-TNF antibody. Regressions of TNF-producing cells occurred in the absence of any demonstrable toxicity in the animals bearing these tumors. TNF-producing tumor cells could function in a paracrine fashion by inhibiting the growth of unmodified, parental tumor cells implanted at the same site. The ability of tumor cells to regress was abrogated by in vivo depletion of CD4+ or CD8+ T cell subsets and animals that had experienced regression of TNF-producing tumors rejected subsequent challenges of parental tumor. Our studies thus show that tumor cells elaborating high local concentrations of TNF regress in the absence of toxicity in the host and that this process requires the existence of intact host immunity. Studies of the lymphocytes infiltrating the gene modified tumors and attempts to use TNF gene modified tumor infiltrating lymphocytes to deliver high local concentrations of TNF to the tumor site without inducing systemic toxicity are underway. C1 NCI,SURG BRANCH,DIV CANC TREATMENT,BLDG 10,ROOM 2B46,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. COLUMBUS HOSP,DEPT PATHOL,GREAT FALLS,MT 59405. GENENTECH INC,DEPT MOLEC IMMUNOL,SAN FRANCISCO,CA 94080. CETUS CORP,DEPT MOLEC BIOL,EMERYVILLE,CA 94608. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 43 TC 344 Z9 347 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1991 VL 146 IS 9 BP 3227 EP 3234 PG 8 WC Immunology SC Immunology GA FJ133 UT WOS:A1991FJ13300051 PM 2016545 ER PT J AU QIAN, JH TITUS, JA ANDREW, SM MEZZANZANICA, D GARRIDO, MA WUNDERLICH, JR SEGAL, DM AF QIAN, JH TITUS, JA ANDREW, SM MEZZANZANICA, D GARRIDO, MA WUNDERLICH, JR SEGAL, DM TI HUMAN PERIPHERAL-BLOOD LYMPHOCYTES TARGETED WITH BISPECIFIC ANTIBODIES RELEASE CYTOKINES THAT ARE ESSENTIAL FOR INHIBITING TUMOR-GROWTH SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER CELLS; AUTOREACTIVE T-CELLS; CYTO-TOXIC FACTOR; MONOCLONAL-ANTIBODIES; NECROSIS FACTOR; RECEPTOR ANTIBODIES; COLORIMETRIC ASSAY; HUMAN B; ANTIGEN; ANTI-T3 AB We have compared the mechanisms by which human PBL targeted with bispecific antibodies either lyse tumor cells or block their growth in culture or in mice. We found that resting PBL were unable to mediate lysis, but were able to block tumor growth. Moreover, targeted PBL were unable to lyse bystander cells, whereas targeted PBL did block the growth of bystander tumor cells in culture and in nude mice. Supernatants from cultures of targeted PBL, or from PBL grown on anti-CD3-coated flasks, blocked the growth of tumor cells in the absence of added effector cells, and antibodies against TNF-alpha and IFN-gamma reversed the inhibition of tumor growth, but had no effect upon cytolysis mediated by targeted by PBL. Our results show that targeted human PBL mediate two different antitumor activities: lysis, which occurs rapidly and requires the direct attachment of the target cell to the cytotoxic cell, and tumor growth inhibition, which is mediated by cytokines released into the medium as a result of receptor cross-linking. The inhibition of bystander tumor growth in mice by targeted PBL suggests that factor release is sufficient to block tumor growth in vivo. Targeted factor release therefore provides a mechanism by which targeted PBL could block the growth of tumor cells in vivo that were not bound by the effector cells, but which were located in the vicinity of tumor cells that were bound. RP QIAN, JH (reprint author), NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. RI Mezzanzanica, Delia/C-2607-2017 OI Mezzanzanica, Delia/0000-0002-9664-6871 NR 56 TC 53 Z9 53 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1991 VL 146 IS 9 BP 3250 EP 3256 PG 7 WC Immunology SC Immunology GA FJ133 UT WOS:A1991FJ13300054 PM 1826709 ER PT J AU LUCEY, DR MCGUIRE, SA CLERICI, M HALL, K BENTON, J BUTZIN, CA WARD, WW SHEARER, G BOSWELL, RN HENDRIX, CW AF LUCEY, DR MCGUIRE, SA CLERICI, M HALL, K BENTON, J BUTZIN, CA WARD, WW SHEARER, G BOSWELL, RN HENDRIX, CW TI COMPARISON OF SPINAL-FLUID BETA-2-MICROGLOBULIN LEVELS WITH CD4+ T-CELL COUNT, INVITRO T-HELPER CELL-FUNCTION, AND SPINAL-FLUID IGG PARAMETERS IN 163 NEUROLOGICALLY NORMAL ADULTS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CENTRAL NERVOUS-SYSTEM; AIDS-RELATED COMPLEX; BLOOD-BRAIN-BARRIER; CEREBROSPINAL-FLUID; BETA-2 MICROGLOBULIN; SERUM BETA-2-MICROGLOBULIN; HIV INFECTION; HTLV-III; BETA2-MICROGLOBULIN; DYSFUNCTION AB beta-2-microglobulin levels were measured in the cerebrospinal fluid (CSF) and serum of 163 human immunodeficiency virus-positive (HIV+) persons with normal neurologic physical examinations. None were on antiretroviral therapy. Only 3% had a positive CSF HIV p24 antigen test. The CSF beta-2-microglobulin levels increased as the CD4+ T cell count decreased. Intrathecal production of beta-2-microglobulin was suggested by finding CSF concentrations greater than serum concentrations in 15% of patients. The CSF beta-2-microglobulin levels rose as in vitro T helper cell function deteriorated, independent of CD4+ T cell count. CSF beta-2-microglobulin levels paralleled CSF IgG, IgG index, and IgG synthesis. Higher CSF beta-2-microglobulin levels were found in persons with positive CSF oligoclonal bands. CSF beta-2-microglobulin concentration may serve as a marker for subclinical neurologic damage due to HIV. If this is established, defining the effect of anti-HIV interventions on CSF beta-2-microglobulin would be warranted. C1 WILFORD HALL USAF MED CTR,DEPT MED,LACKLAND AFB,TX 78236. WILFORD HALL USAF MED CTR,DEPT NEUROL,LACKLAND AFB,TX 78236. WILFORD HALL USAF MED CTR,DEPT PATHOL,LACKLAND AFB,TX 78236. WILFORD HALL USAF MED CTR,CLIN INVEST DIRECTORATE,LACKLAND AFB,TX 78236. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 39 TC 19 Z9 19 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 MAY PY 1991 VL 163 IS 5 BP 971 EP 975 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FH745 UT WOS:A1991FH74500006 PM 1673466 ER PT J AU HIRSCH, VM ZACK, PM VOGEL, AP JOHNSON, PR AF HIRSCH, VM ZACK, PM VOGEL, AP JOHNSON, PR TI SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION OF MACAQUES - END-STAGE DISEASE IS CHARACTERIZED BY WIDESPREAD DISTRIBUTION OF PROVIRAL DNA IN TISSUES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL; PERIPHERAL-BLOOD; III INFECTION; HTLV-III/LAV; ANEMIA VIRUS; LYMPH-NODES; AIDS; RETROVIRUS; LENTIVIRUS; MONKEYS AB Four simian immunodeficiency virus (SIV)-infected macaques in the terminal stages of AIDS were studied. Easily detectable unintegrated proviral DNA was present in nearly every tissue (lymphoid and nonlymphoid) examined. SIV-specific immunohistochemistry revealed that macrophages or macrophage-like cells were the predominant reservoirs for SIV. High burdens of infectious SIV were also characteristic of end-stage disease. At the molecular level, sequence analyses of molecular clones derived directly from tissue demonstrated that SIV, like other RNA viruses, exists as a mixture of closely related genomes. Viruses derived by cocultivation seemed to be selected for their ability to grow in tissue culture and did not represent the wide spectrum of genotypes in tissues. These data indicate that SIV-induced immunodeficiency is a complex, multisystem disease and that SIV replication, in addition to impairing the immune system, may have direct deleterious effects on multiple organ systems. C1 GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,RETROVIRAL PATHOGENESIS SECT,WASHINGTON,DC 20007. USA,MED RES INST INFECT DIS,DIV PATHOL,FREDERICK,MD 21701. RP HIRSCH, VM (reprint author), NIAID,INFECT DIS LAB,TWINBROOK 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Johnson, Philip/A-6892-2009 FU NIAID NIH HHS [AI-72623] NR 42 TC 84 Z9 84 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 MAY PY 1991 VL 163 IS 5 BP 976 EP 988 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FH745 UT WOS:A1991FH74500007 PM 2019773 ER PT J AU STEINHOFF, MC HALSEY, NA FRIES, LF WILSON, MH KING, J BURNS, BA SAMORODIN, RK PERKIS, V MURPHY, BR CLEMENTS, ML AF STEINHOFF, MC HALSEY, NA FRIES, LF WILSON, MH KING, J BURNS, BA SAMORODIN, RK PERKIS, V MURPHY, BR CLEMENTS, ML TI THE A/MALLARD/6750/78 AVIAN-HUMAN, BUT NOT THE A/ANN-ARBOR/6/60 COLD-ADAPTED, INFLUENZA-A KAWASAKI/86 (H1N1) REASSORTANT VIRUS-VACCINE RETAINS PARTIAL VIRULENCE FOR INFANTS AND CHILDREN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TEMPERATURE-SENSITIVE PHENOTYPE; SERONEGATIVE ADULT VOLUNTEERS; YOUNG-CHILDREN; WILD-TYPE; DOSE-RESPONSE; INACTIVATED VACCINE; NATURAL INFECTION; PROTEIN GENES; B-VIRUS; LIVE AB Characteristics of avian-human (ah) and cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant vaccine viruses were compared in 37 seronegative adults and 122 seronegative infants and children. The 50% human infectious dose (HID50) in infants and children was 10(2.9) and 10(2.6) TCID50 for the ah and ca vaccine, respectively. The ah influenza A/Kawasaki/9/86 reassortant was reactogenic: 24% of infants and children infected with greater-than-or-equal-to 100 HID50 had fever greater-than-or-equal-to 39.4-degrees-C. Since H3N2 ah vaccines were previously shown to be adequately attenuated, it is reasonable to suggest that the genes that code for hemagglutinin and neuraminidase of the H1N1 virus apparently influence the reactogenicity of reassortant viruses derived from the avian influenza A/Mallard/New York/6750/78 donor virus. Because this avian virus does not reproducibly confer a satisfactory level of attenuation to each subtype of influenza A virus, it is not a suitable donor virus for attenuation of wild-type influenza viruses. In contrast, the ca A/Ann Arbor/6/60 donor virus reliably confers attenuation characteristics to a variety of H1N1 and H3N2 influenza A viruses. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP STEINHOFF, MC (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,CTR IMMUNIZAT RES,HAMPTON HOUSE,ROOM 125,BALTIMORE,MD 21218, USA. FU NIAID NIH HHS [AI-62515] NR 39 TC 46 Z9 46 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 MAY PY 1991 VL 163 IS 5 BP 1023 EP 1028 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FH745 UT WOS:A1991FH74500013 PM 2019751 ER PT J AU LIPSCHIK, GY MASUR, H KOVACS, JA AF LIPSCHIK, GY MASUR, H KOVACS, JA TI POLYAMINE METABOLISM IN PNEUMOCYSTIS-CARINII SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TRYPANOSOMA-BRUCEI-BRUCEI; ACQUIRED IMMUNODEFICIENCY SYNDROME; DL-ALPHA-DIFLUOROMETHYLORNITHINE; ORNITHINE DECARBOXYLASE; DIHYDROFOLATE-REDUCTASE; ANTIMICROBIAL AGENTS; PNEUMONIA; RNA; INHIBITION; INVITRO AB alpha-difluoromethylornithine (DFMO) is being used to treat Pneumocystis carinii pneumonia despite a lack of in vitro evidence supporting its antipneumocystis activity. DFMO is a specific inhibitor of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis. To investigate polyamine metabolism in P. carinii, extracts of the organism were analyzed for polyamine content and ornithine decarboxylase activity, and [H-3]ornithine and [C-14]arginine incorporation into polyamines during short-term culture was determined. P. carinii extracts contained putrescine and spermidine in a ratio of 0.17:1; traces of spermine were detected. Although ornithine decarboxylase activity was not detected, P. carinii incorporated ornithine and arginine into putrescine and spermidine but not into spermine, suggesting that the spermine detected derived from contaminating host cells. Uninfected rat lung incorporated ornithine minimally. Pentamidine, DFMO, and alpha-monofluoromethyldehydroornithine methyl ester inhibited ornithine incorporation by up to 86% at clinically achievable concentrations. These data provide a rationale for using polyamine synthesis antagonists in P. carinii pneumonia and a method for screening antipneumocystis drugs in vitro. RP LIPSCHIK, GY (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,ROOM 10D48,BETHESDA,MD 20892, USA. NR 48 TC 8 Z9 8 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 MAY PY 1991 VL 163 IS 5 BP 1121 EP 1127 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FH745 UT WOS:A1991FH74500028 PM 2019760 ER PT J AU NUTMAN, TB STEEL, C WARD, DJ ZEAFLORES, G OTTESEN, EA AF NUTMAN, TB STEEL, C WARD, DJ ZEAFLORES, G OTTESEN, EA TI IMMUNITY TO ONCHOCERCIASIS - RECOGNITION OF LARVAL ANTIGENS BY HUMANS PUTATIVELY IMMUNE TO ONCHOCERCA-VOLVULUS INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INDIVIDUALS; EXPRESSION AB Immunoblot analyses were done using sera from 12 individuals without evidence of onchocerciasis and 16 with active infection from an area of Guatemala holoendemic for onchocerciasis. For adult antigens from Onchocerca volvulus, no differences in antigen recognition could be identified between the two groups. In contrast, when infective larval (L3) antigen preparations derived from the related animal parasite Onchocerca lienalis were used, IgG from the "immune" individuals preferentially recognized a 45- to 50-kDa triplet and a 22-kDa L3 antigen. When L3 antigens of Brugia malayi were used, sera from putatively immune individuals identified a high-molecular-weight triplet/quadruplet plus several additional antigens of lower molecular weights that were recognized by sera from few (or none) of the infected patients. These findings define some differences in antibody specificity in onchocerciasis patients and therefore might define potential target antigens of humoral host defense. The exact nature of such defenses is unknown. C1 MINIST HLTH,GUATEMALA CITY,GUATEMALA. RP NUTMAN, TB (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 22 TC 36 Z9 36 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1991 VL 163 IS 5 BP 1128 EP 1133 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FH745 UT WOS:A1991FH74500029 PM 2019761 ER PT J AU KAN, VL BENNETT, JE AF KAN, VL BENNETT, JE TI BETA-1,4-OLIGOGLUCOSIDES INHIBIT THE BINDING OF ASPERGILLUS-FUMIGATUS CONIDIA TO HUMAN MONOCYTES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID ALTERNATIVE COMPLEMENT PATHWAY; BETA-GLUCAN RECEPTOR; PHAGOCYTOSIS; MACROPHAGES AB The binding of Aspergillus fumigatus conidia to human monocytes is mediated by a barley beta-glucan-inhibitable receptor. The simplest linkages in this glucan are present in the disaccharides laminaribiose (beta-1,3) and cellobiose (beta-1,4). Although laminaribiose gave strong inhibition of conidial binding to monocytes, cellobiose and oligosaccharides with beta-1,4-linked glucose residues were more potent as specific inhibitors of this binding over similar concentrations. Increasing the number of beta-1,4-linked glucose residues led to greater inhibition of conidial binding by human monocytes. RP KAN, VL (reprint author), NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BLDG 10,RM 11N107,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 13 TC 22 Z9 23 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 MAY PY 1991 VL 163 IS 5 BP 1154 EP 1156 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FH745 UT WOS:A1991FH74500036 PM 2019764 ER PT J AU LEONARD, EJ YOSHIMURA, T TANAKA, S RAFFELD, M AF LEONARD, EJ YOSHIMURA, T TANAKA, S RAFFELD, M TI NEUTROPHIL RECRUITMENT BY INTRADERMALLY INJECTED NEUTROPHIL ATTRACTANT ACTIVATION PROTEIN-1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CHEMOTACTIC FACTOR MDNCF; HUMAN MONOCYTE; HUMAN-SKIN; PEPTIDE; INTERLEUKIN-1; HISTAMINE; SEQUENCE; PURIFICATION; LEUKOCYTES; RELEASE AB Neutrophil attractant/activation protein-1 (NAP-1) is a recently described cytokine that attracts neutrophils, but not monocytes or eosinophils. This leukocyte specificity is not absolute, in that NAP-1 attracts basophils and small numbers of lymphocytes. Our purpose was to determine in vivo effects of NAP-1, and to compare them to the reported action of the complement attractant, C5a. Intradermal injection into normal human subjects of 40-mu-l of NAP-1, over a concentration range of 4 x 10(-8) M to 10(-6) M, caused no symptoms or signs such as wheal-and-flare, itching, induration, or tenderness. However, biopsies of injection sites showed perivascular neutrophil infiltration as early as 30 min, which increased at 1 and 3 h. The mean number of neutrophils per mm2 of dermis for 15 biopsies taken 3 h after intradermal injection of 2 x 10(-7) M or 10(-6) M NAP-1 was 164 +/- 41; the response to saline or a NAP-1 inactive fragment was 5 or less. Intradermal NAP-1 did not cause basophil or lymphocyte infiltration. Consistent with the absence of a wheal-and-flare, acid toluidine blue-stained sections showed no evidence of mast cell degranulation, in contrast to previously reported results with C5a. Thus, the predominant response by human subjects to intradermal NAP-1 was neutrophil accumulation in proximity to dermal blood vessels. C1 NCI,CHEM SECT,CELL BIOL LAB,BETHESDA,MD 20892. NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. RP LEONARD, EJ (reprint author), NCI,FCRDC,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,BLDG 560,RM 12-71,FREDERICK,MD 21702, USA. NR 29 TC 100 Z9 100 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1991 VL 96 IS 5 BP 690 EP 694 DI 10.1111/1523-1747.ep12470612 PG 5 WC Dermatology SC Dermatology GA FK303 UT WOS:A1991FK30300006 PM 2022877 ER PT J AU LICHTI, U WEINBERG, WC YUSPA, SH AF LICHTI, U WEINBERG, WC YUSPA, SH TI PROPERTIES OF MURINE PELAGE HAIR-FOLLICLES IN MONOLAYER AND COLLAGEN MATRIX CULTURES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article RP LICHTI, U (reprint author), NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,BETHESDA,MD 20892, USA. RI Weinberg, Wendy/A-8920-2009 NR 5 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1991 VL 96 IS 5 BP S81 EP S82 DI 10.1111/1523-1747.ep12472042 PG 2 WC Dermatology SC Dermatology GA FK303 UT WOS:A1991FK30300039 PM 2022891 ER PT J AU MOSHELL, AN PRICE, VH HEADINGTON, JT BYSTRYN, JC AF MOSHELL, AN PRICE, VH HEADINGTON, JT BYSTRYN, JC TI SUPPLEMENT ON THE RESEARCH WORKSHOP - ALOPECIA-AREATA LISTER-HILL-NATIONAL-CENTER, NATIONAL-INSTITUTES-OF-HEALTH, BETHESDA, MARYLAND, OCTOBER 25 AND 26, 1990 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material C1 NATL ALOPECIA AREATA FDN,SAN RAFAEL,CA. RP MOSHELL, AN (reprint author), NIAMSD,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1991 VL 96 IS 5 BP S67 EP S67 DI 10.1111/1523-1747.ep12471862 PG 1 WC Dermatology SC Dermatology GA FK303 UT WOS:A1991FK30300027 ER PT J AU EGGERMAN, TL HOEG, JM MENG, MS TOMBRAGEL, A BOJANOVSKI, D BREWER, HB AF EGGERMAN, TL HOEG, JM MENG, MS TOMBRAGEL, A BOJANOVSKI, D BREWER, HB TI DIFFERENTIAL TISSUE-SPECIFIC EXPRESSION OF HUMAN APOA-L AND APOA-LL-1 SO JOURNAL OF LIPID RESEARCH LA English DT Article DE APOLIPOPROTEINS; CACO-2; SMALL INTESTINE; HIGH DENSITY LIPOPROTEINS; LIPID METABOLISM ID APOLIPOPROTEIN-A-II; HIGH-DENSITY-LIPOPROTEIN; CHOLESTEROL ACYLTRANSFERASE ACTIVITY; HEPATIC TRIGLYCERIDE LIPASE; CORONARY-ARTERY DISEASE; NUCLEIC-ACID SEQUENCE; THORACIC-DUCT LYMPH; MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; HEART-DISEASE AB To evaluate the sources of high density lipoprotein (HDL) particles containing only apolipoprotein A-I (apoA-I), the synthesis of apoA-I and apolipoprotein A-II (apoA-II) was examined in human liver and small intestine as well as the human intestinally derived cell line, Caco-2. Human liver contained apoA-I, apoA-II as well as apolipoprotein B (apoB) mRNA. In contrast, human adult small intestine total and polyA* RNA had little or no apoA-II despite the presence of apoA-I and apoB. Intestinal biopsies from normal individuals failed to show de novo apoA-II protein synthesis in the media of organ cultures during [S-35]methionine pulse-chase labeling, whereas apoA-I could be readily detected. Caco-2 cells contained apoA-II mRNA and secreted apoA-II protein into the tissue culture media. These data indicate that the primary site of human apoA-II synthesis is in the liver and that the small intestine secretes apoA-I-containing high density lipoproteins. C1 HANOVER MED SCH,ZENTRUM INNERE MED,W-3000 HANNOVER 61,GERMANY. RP EGGERMAN, TL (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N-117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 62 TC 49 Z9 52 U1 1 U2 1 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 MAY PY 1991 VL 32 IS 5 BP 821 EP 828 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM980 UT WOS:A1991FM98000009 PM 1649244 ER PT J AU TABOR, E KIM, CM AF TABOR, E KIM, CM TI INHIBITION OF HUMAN HEPATOCELLULAR-CARCINOMA AND HEPATOBLASTOMA CELL-LINES BY DEFEROXAMINE SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE CALCIUM DISODIUM VERSENATE (EDTA); CANCER CHEMOTHERAPY; CELL LINES; HEPATITIS-B VIRUS ID ANTINEUROBLASTOMA ACTIVITY; FERRITIN SYNTHESIS; CHELATING-AGENTS; DNA-SYNTHESIS; IRON; INVITRO; DESFEROXAMINE; SECRETION; LEUKEMIA; GROWTH AB Inhibition of human hepatocellular carcinoma (PLC/PRF/5 and Hep3B) or hepatoblastoma (Hep G2) cell lines by inclusion of deferoxamine mesylate (desferrioxamine) (DFX) in the culture medium was evaluated. When PLC/PRF/5 cells were maintained for 7 days in 30 or 60-mu-M DFX, the cell number was decreased by 30-60%, little or no alpha-fetoprotein (AFP) was produced, and supernatant endpoint dilution tilters of hepatitis B surface antigen (HBsAg) were reduced 1-2 logs. PLC/PRF/5 cells maintained for 7 days without DFX (simultaneous controls) grew to confluence, produced AFP that reached 10-60 ng/ml in the supernate, and the HBsAg titer remained constant or increased 1 log. Similar effects were observed in Hep3B and Hep G2 cells maintained in DFX (except that Hep G2 cells do not produce HBsAg), compared to simultaneous control cells grown in the absence of DFX. The growth of a human embryonic lung fibroblast cell line (Wl-38) was not significantly inhibited by DFX, although it grew at a slower rate than simultaneous control cells grown without DFX. Subsequent growth in FeSo4 of PLC/PRF/5, Hep3B, and Hep G2 cells that previously had been maintained in DFX did not reverse the effects of DFX. PLC/PRF/5 cells were also inhibited when maintained in medium containing equimolar concentrations of DFX and FeCl3 and in medium containing equimolar concentrations of DFX and FeSO4. PLC/PRF/5 cells were not inhibited by maintenance in up to 60-mu-M of another chelating agent that has a similar affinity for iron, calcium disodium versenate (EDTA). These studies show that DFX inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cell lines regardless of the presence (PLC/PRF/5, Hep3B) or absence (Hep G2) of integrated hepatitis B virus DNA. The findings also suggest that the inhibition may have been due to mechanisms other than iron chelation. RP TABOR, E (reprint author), NCI,BETHESDA,MD 20892, USA. NR 24 TC 8 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAY PY 1991 VL 34 IS 1 BP 45 EP 50 DI 10.1002/jmv.1890340108 PG 6 WC Virology SC Virology GA FN180 UT WOS:A1991FN18000007 PM 1715897 ER PT J AU DECOSTA, BR LEWIN, AH RICE, KC SKOLNICK, P SCHOENHEIMER, JA AF DECOSTA, BR LEWIN, AH RICE, KC SKOLNICK, P SCHOENHEIMER, JA TI NOVEL SITE-DIRECTED AFFINITY LIGANDS FOR GABA-GATED CHLORIDE CHANNELS - SYNTHESIS, CHARACTERIZATION, AND MOLECULAR MODELING OF 1-(ISOTHIOCYANATOPHENYL)-4-TERT-BUTYL-2,6,7-TRIOXABICYCLO[2.2.2]OCTANES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PERIPHERAL BENZODIAZEPINE RECEPTORS; CONVULSANTS; IONOPHORE; BINDING; ESTERS AB p-,m-, and o-isothiocyanate derivatives (1-3, respectively) of tert-butylbicycloorthobenzoate (TBOB) were synthesized from 3-tert-butyloxetane-3-methanol (4) as the starting material. While 2 was readily obtained in four steps via catalytic hydrogenation of the m-nitro-tert-butylbicycloorthobenzoate (9) intermediate, 1 and 3 could not be obtained this way. 1 and 3 were instead synthesized by an alternative four-step approach which made use of the stability of the isothiocyanate moiety to strong Lewis acids such as boron trifluoride etherate, conditions that would isomerize isothiocyanato oxetane ester intermediates to their corresponding orthoesters. The p-isothiocyanate derivative of TBOB, compound 1, inhibited [S-35]-tert-butylbicyclophosphorothionate (TBPS) binding to rat cortical membranes with a potency (IC50 62 nM) comparable to the parent compound while 2 and 3 were approximately 10-fold less potent (IC50 values 570 and 609 nM, respectively). Preincubating tissue with radioligand further reduced the potencies of 2 and 3 by approximately 1 order of magnitude (IC50 values 5400 and 7500 nM, respectively) while the potency of 1 (IC50 90 nM) was only marginally affected by this procedure. Pretreatment of membranes with 1 and 2 followed by extensive washing resulted in a concentration-dependent inhibition of [S-35]TBPS binding. In contrast, preincubating tissues with up to 2.4-mu-M of 3 did not elicit an apparent acylation of [S-35]TBPS binding sites. Molecular modeling of the effective diameters of 1-3 in their thermodynamically most stable conformations indicates a relationship between these diameters and their relative efficacies as site-directed acylators; the smaller the diameter, the more potent the acylator. This hypothesis explains both the relative potencies of these compounds and their differential abilities to acylate the TBPS binding site. C1 NIDDKD,MED CHEM LAB,BLDG 8,RM B1 23,BETHESDA,MD 20892. RES TRIANGLE INST,DEPT CHEM & LIFE SCI,RES TRIANGLE PK,NC 27709. NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NR 18 TC 12 Z9 12 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 MAY PY 1991 VL 34 IS 5 BP 1531 EP 1538 DI 10.1021/jm00109a002 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA FL859 UT WOS:A1991FL85900002 PM 2033577 ER PT J AU BURKE, TR LI, ZH BOLEN, JB MARQUEZ, VE AF BURKE, TR LI, ZH BOLEN, JB MARQUEZ, VE TI PHOSPHONATE-CONTAINING INHIBITORS OF TYROSINE-SPECIFIC PROTEIN-KINASES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; FACTOR-RECEPTOR; FACTOR-I; ERBSTATIN; INSULIN; CARCINOMAS; CELLS; OVEREXPRESSION; AMPLIFICATION; ASSOCIATION AB Tyrosine-specific protein kinases (TPK) are important signal transducing enzymes involved in normal cellular growth and differentiation and have been implicated in the etiology of a number of human neoplastic processes. Efforts to develop agents which inhibit the function of these enzymes by interfering with the binding of substrate have been limited by the lack of detailed three-dimensional structural data. Many inhibitors of substrate binding share a common styrene nucleus 1 which has been postulated to function as a conformationally constrained analogue of tyrosine. In an effort to develop high-affinity compounds based on this hypothesis, a number of derivatives were synthesized in which either methylphosphonate (4a-c) or (hydroxymethyl)phosphonate (3a-c) were appended to the aromatic 4-position of styrene-containing moieties. The intent of this approach was to prepare hydrolytically stable analogues which expressed additional enzyme recognition features present during the phosphorylation of tyrosine itself. None of the analogues showed inhibitory activity up to the maximum concentration tested (1000-mu-M) when assayed against autophosphorylation of A-431 derived epidermal growth factor receptor (EGFR) or p56lck (autophosphorylation and transphosphorylation of rabbit muscle enolase). Additionally, a series of naphthalene-based inhibitors including (1-naphthalenylhydroxymethyl)phosphonic acid (14), its known 2-positional isomer 16, and sulfonate (19, 20) and phosphate derivatives (17, 18) were also tested under similar conditions. Only (2-naphthalenylhydroxymethyl)phosphonic acid (16) showed activity (IC50 = 250-mu-M in EGFR, in agreement with the reported literature value). These results suggest that the interaction of styrene-based inhibitors with the substrate binding domain of TPKS may not occur in a manner analogous to the interaction of tyrosine with this domain. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. RP BURKE, TR (reprint author), NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BLDG 37,RM 5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 59 TC 52 Z9 52 U1 0 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 MAY PY 1991 VL 34 IS 5 BP 1577 EP 1581 DI 10.1021/jm00109a008 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA FL859 UT WOS:A1991FL85900008 PM 2033582 ER PT J AU MURAKAMI, K SHIRASAKA, T YOSHIOKA, H KOJIMA, E AOKI, S FORD, H DRISCOLL, JS KELLEY, JA MITSUYA, H AF MURAKAMI, K SHIRASAKA, T YOSHIOKA, H KOJIMA, E AOKI, S FORD, H DRISCOLL, JS KELLEY, JA MITSUYA, H TI ESCHERICHIA-COLI MEDIATED BIOSYNTHESIS AND INVITRO ANTI-HIV ACTIVITY OF LIPOPHILIC 6-HALO-2',3'-DIDEOXYPURINE NUCLEOSIDES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID AIDS-RELATED COMPLEX; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; PLACEBO-CONTROLLED TRIAL; PHASE-I TRIAL; ZIDOVUDINE AZT; 2',3'-DIDEOXYINOSINE DDI; ADENINE-ARABINOSIDE; AZIDOTHYMIDINE AZT; VIRUS-INFECTION AB A series of 6-substituted 2',3'-dideoxypurine ribofuranosides (ddP) was enzymatically synthesized with live E. coli in an effort to enhance the lipophilicity of this class of anti-human immunodeficiency virus (HIV) compounds and thereby facilitate drug delivery into the central nervous system. All 6-halo-substituted ddPs were substantially more lipophilic, as defined by their octanol-water partition coefficient (P), than their nonhalogenated congeners 2',3'-dideoxyinosine (ddI) or 2',3'-dideoxyguanosine (ddG). For this class of compounds, log P's ranged from +0.5 to -1.2 in the following order: 6-iodo, 2-amino-6-iodo > 6-bromo, 2-amino-6-bromo > 6-chloro, 2-amino-6-chloro > 6-fluoro, 2-amino-6-fluoro >> ddG > ddI. These compounds were evaluated in vitro for ability to suppress the infectivity, replication, and cytopathic effect of HIV. 2-Amino-6-fluoro-, 2-amino-6-chloro-, and 6-fluoro-ddP exhibited a potent activity against HIV comparable to that of ddI or ddG and completely blocked the infectivity of HIV without affecting the growth of target cells. The comparative order of in vitro anti-HIV activity was 2-amino-6-fluoro, 2-amino-6-chloro, 6-fluoro > 2-amino-6-bromo > 2-amino-6-iodo, 6-chloro > 6-bromo > 6-iodo. These compounds also exhibited potent in vitro activity against HIV-2 and 3'-azido-3'-deoxythymidine-resistant HIV-1 variants. All 2-amino-6-halo-ddPs and 6-halo-ddPs were substrates for adenosine deaminase (ADA) and were converted to ddG or ddI, respectively. In the presence of the potent ADA inhibitor 2'-deoxycoformycin, 6-halo-substituted ddPs failed to exert an in vitro antiretroviral effect. These dideoxypurine nucleoside analogues represent a new class of lipophilic prodrugs of ddG and ddI that possess the potential for more effective therapy of HIV-induced neurologic disorders. C1 NCI,CLIN ONCOL PROGRAM,BLDG 10,ROOM 13N248,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,MED CHEM LAB,BETHESDA,MD 20892. SANYO KOKUSAKU PULP CO,BIORESOURCES RES LAB,IWAKUNI 740,JAPAN. NR 48 TC 40 Z9 40 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 MAY PY 1991 VL 34 IS 5 BP 1606 EP 1612 DI 10.1021/jm00109a012 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA FL859 UT WOS:A1991FL85900012 PM 2033586 ER PT J AU BARCHI, JJ MARQUEZ, VE DRISCOLL, JS FORD, H MITSUYA, H SHIRASAKA, T AOKI, S KELLEY, JA AF BARCHI, JJ MARQUEZ, VE DRISCOLL, JS FORD, H MITSUYA, H SHIRASAKA, T AOKI, S KELLEY, JA TI POTENTIAL ANTI-AIDS DRUGS - LIPOPHILIC, ADENOSINE DEAMINASE-ACTIVATED PRODRUGS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; CEREBROSPINAL-FLUID; 2',3'-DIDEOXYPURINE NUCLEOSIDES; TUBERCULOUS MENINGITIS; BRAIN; INFECTIVITY; INVITRO; 2',3'-DIDEOXYADENOSINE; DIDEOXYNUCLEOSIDES AB Selected acid-stable (2'-fluoro-2',3'-dideoxyarabinofuranosyl)adenine nucleosides containing methyl groups and other lipophilic functions at various positions in the adenine ring were prepared and evaluated as anti-HIV agents. The N6-methyl (1f), N6-benzoyl (1g), and 6-chloro (li) analogues had modest activity, giving 30-50% protection to ATH8 cells infected with HIV. 2-Methyl (1d), 8-methyl (1h), and 2,N6-dimethyl (1e) substitution, as well as N1-oxide (21) formation, abolished the activity of the parent compound (1a). Several of these compounds, originally designed as agents for treating HIV in the central nervous system, were further investigated as substrates for adenosine deaminase (ADA). Kinetic experiments showed that ADA catalyzed the formation of the anti-HIV active inosine compound 1b from the N6-methyl analogue 1f in a quantitative manner. The anti-HIV activity of 1f and 1i was abolished when the ADA inhibitor, 2'-deoxycoformycin, was added to the test mixture. In contrast, the activity of 1f was significantly enhanced when ADA was added to the test system. These data indicate that 1f and 1i are prodrug forms of 1b in systems containing ADA. C1 NCI,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RI Barchi Jr., Joseph/N-3784-2014 NR 44 TC 80 Z9 80 U1 1 U2 4 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 MAY PY 1991 VL 34 IS 5 BP 1647 EP 1655 DI 10.1021/jm00109a018 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA FL859 UT WOS:A1991FL85900018 PM 2033591 ER PT J AU DIAZARAUZO, H EVONIUK, GE SKOLNICK, P COOK, JM AF DIAZARAUZO, H EVONIUK, GE SKOLNICK, P COOK, JM TI THE AGONIST PHARMACOPHORE OF THE BENZODIAZEPINE RECEPTOR - SYNTHESIS OF A SELECTIVE ANTICONVULSANT ANXIOLYTIC SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Letter ID INVERSE AGONIST; BETA-CARBOLINES; BINDING; ANTAGONISTS; LIGANDS; DERIVATIVES; SERIES; SITE; ACID C1 UNIV WISCONSIN,DEPT CHEM,MILWAUKEE,WI 53201. NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. FU NIMH NIH HHS [MH 46851] NR 36 TC 39 Z9 39 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 MAY PY 1991 VL 34 IS 5 BP 1754 EP 1756 DI 10.1021/jm00109a035 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA FL859 UT WOS:A1991FL85900035 PM 1674542 ER PT J AU CENA, V BROCKLEHURST, KW POLLARD, HB ROJAS, E AF CENA, V BROCKLEHURST, KW POLLARD, HB ROJAS, E TI PERTUSSIS TOXIN STIMULATION OF CATECHOLAMINE RELEASE FROM ADRENAL-MEDULLARY CHROMAFFIN CELLS - MECHANISM MAY BE BY DIRECT ACTIVATION OF L-TYPE AND G-TYPE CALCIUM CHANNELS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE CATECHOLAMINE SECRETION; MEDULLARY CHROMAFFIN CELL; PERTUSSIS TOXIN; G-TYPE CA2+ CHANNEL; L-TYPE CA2+ CHANNEL; G-PROTEIN ID PROTEIN; SECRETION; RECEPTOR; GRANULE AB We have previously shown that pertussis toxin (PTX) stimulates delayed-onset, [Ca2+]o-dependent catecholamine (CA) release from bovine chromaffin cells. We now show that this effect of PTX is inhibited in part (50%) by dihydropyridine Ca2+-channel antagonists niludipine and nifedipine, and is potentiated by the dihydropyridine Ca2+-channel agonist Bay K-8644. We and others have shown that pretreatment of chromaffin cells with PTX results in enhanced catecholamine secretion in response to high [K+]o, nicotine and muscarine, and here we extend these observations by showing that toxin pretreatment also enhances the secretory response to [Ba2+]o. All these data are consistent with the concept that PTX may act on Ca2+ channels. To examine the possibility of a direct action of the toxin on the voltage-gated L-type Ca2+ channel known to be present in these cells, we studied the effects of the toxin on whole cell Ca2+ currents. We found and report here that spontaneous electrical activity was considerably increased in PTX-treated cells. Our measurements of whole cell inward Ca2+ currents indicate that the underlying mechanism is a marked shift of the activation curve of the L-type Ca2+ current along the voltage axis towards more negative potentials. While treatment of the cells with PTX had no effect on L-type Ca2+-channel conductance (6 nS/cell at 2.6 mM [Ca2+]o), PTX evoked the activation of a new class of Ca2+-selective channels (5 pS in 25 mM [Ca2+]pipet), which are rather insensitive to membrane potential. We have termed these G-type calcium channels. These data suggest that treatment with PTX not only increases the probability of L-type Ca2+-channel activation at more negative potentials, but also increases the probability of opening of an entirely new, voltage-independent, Ca2+ channel. These actions of PTX should promote Ca2+ entry and might explain the stimulation by the toxin of CA secretion from medullary chromaffin cells in culture. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 23 TC 23 Z9 23 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 MAY PY 1991 VL 122 IS 1 BP 23 EP 31 DI 10.1007/BF01872736 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA FN929 UT WOS:A1991FN92900003 PM 1714959 ER PT J AU MIXSON, AJ PHANG, JM AF MIXSON, AJ PHANG, JM TI STRUCTURAL ANALOGS OF PYRROLINE 5-CARBOXYLATE SPECIFICALLY INHIBIT ITS UPTAKE INTO CELLS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE PROLINE; TRANSPORT; REDOX; AMINO ACIDS; MEMBRANES; TRANSPORT CARRIERS ID RADIOISOTOPIC ASSAY; ACID; COMPLEXES; REAGENTS; AGENT AB Pyrroline 5-carboxylate, a naturally occurring intermediate, is a potent activator of redox-dependent metabolic pathways. This effect of pyrroline 5-carboxylate is due, at least in part, to the special mechanism mediating its entry into cells. Using Chinese hamster ovary cells we recently characterized the cellular uptake of pyrroline 5-carboxylate as a process transferring oxidizing potential pari passu with cell entry, a process consistent with group translocation. We sought to identify specific inhibitors to probe this unique uptake mechanism, to blockade the metabolic effects of pyrroline 5-carboxylate, and to provide strategies to identify the putative carrier protein. Because pyrroline 5-carboxylate, a ring structure with a tertiary nitrogen, is in spontaneous equilibrium with glutamic-gamma-semialdehyde, an open-chain structure, we tested analogues of both. Most open-chain aldehydes at 10 mM had little effect on the uptake of pyrroline 5-carboxylate. Although succinic semialdehyde did inhibit, its effect was nonspecific in that the uptake of alpha(methylamino) isobutyric acid was inhibited as much as the uptake of pyrroline 5-carboxylate. In contrast, pyrroline 2-carboxylate and other cyclic compounds with tertiary nitrogens, e.g., pyridines, were specific inhibitors of pyrroline 5-carboxylate uptake. Respective potencies of pyridine derivatives depended on the nature and location of constituent groups. Kinetics studies showed that these inhibitors were competitive with pyrroline 5-carboxylate and the most potent inhibitor, 2,6-pyridinedicarboxaldehyde, exhibited a K12 of 0.27 +/- 0.05 mM. In the face of their effect on P5C uptake, the most potent of these analogues, 2-pyridinecarboxaldehyde and 2,6-pyridinedicarboxaldehyde, did not inhibit the activity of pyrroline 5-carboxylate reductase, the enzyme that converts pyrroline 5-carboxylate to proline. Nevertheless, the analogues markedly inhibited the stimulatory effect of P5C on the pentose phosphate shunt. Importantly, not only did 2-pyridinecarboxaldehyde protect the pyrroline 5-carboxylate uptake mechanism from the inhibitory effects of a sulfhydryl-reactive agent, but also its inhibitory effect became irreversible in the presence of sodium cyanoborohydride. These inhibitors may help discriminate events mediated by the transport carrier from those mediated by intracellular metabolism and may provide a method for identifying and characterizing the putative carrier for P5C. C1 NCI,METAB BRANCH,ENDOCRINOL SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,NUTR & MOLEC REGULAT LAB,FREDERICK,MD 21701. NR 32 TC 1 Z9 1 U1 0 U2 2 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 MAY PY 1991 VL 121 IS 3 BP 269 EP 277 DI 10.1007/BF01951560 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA FL014 UT WOS:A1991FL01400007 PM 1865491 ER PT J AU BEUTLER, JA CHMURNY, GM LOOK, SA WITHERUP, KM AF BEUTLER, JA CHMURNY, GM LOOK, SA WITHERUP, KM TI TAXININE-M, A NEW TETRACYCLIC TAXANE FROM TAXUS-BREVIFOLIA SO JOURNAL OF NATURAL PRODUCTS LA English DT Article AB The isolation of a novel tetracyclic taxane, taxinine M {1}, from Taxus brevifolia bark and its structure elucidation by spectroscopic methods are reported. RP BEUTLER, JA (reprint author), NCI FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702, USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU NCI NIH HHS [N01-CO-74102] NR 9 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY-JUN PY 1991 VL 54 IS 3 BP 893 EP 897 DI 10.1021/np50075a028 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA GA262 UT WOS:A1991GA26200028 PM 1955887 ER PT J AU SIVAM, SP KRAUSE, JE BREESE, GR HONG, JS AF SIVAM, SP KRAUSE, JE BREESE, GR HONG, JS TI DOPAMINE-DEPENDENT POSTNATAL-DEVELOPMENT OF ENKEPHALIN AND TACHYKININ NEURONS OF RAT BASAL GANGLIA SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE DOPAMINE; 6-HYDROXYDOPAMINE; ENKEPHALIN; SUBSTANCE-P; STRIATUM ID DEPLETING BRAIN-LESIONS; CENTRAL NERVOUS-SYSTEM; PERFORMANCE LIQUID-CHROMATOGRAPHY; PREPROENKEPHALIN MESSENGER-RNA; LESCH-NYHAN SYNDROME; SUBSTANCE-P; GENE-EXPRESSION; PARKINSONS-DISEASE; TOPOGRAPHICAL DISTRIBUTION; ELECTROCHEMICAL DETECTION AB The influence of deprivation of the neurotransmitter dopamine (DA) on the development of [Met5]-enkephalin (ME) and substance P (SP) neuropeptide systems of the striatum was investigated in Sprague-Dawley rats. The neurotoxin 6-hydroxydopamine (6-OHDA) was used to induce DA deficiency on postnatal day 3 in rats, and the animals were killed at different postnatal time points until 35 days of age. The levels of ME and SP were determined by radioimmunoassay, and the abundance of preproenkephalin (PPE) and preprotachykinin (PPT) mRNA in the striatum was assessed by Northern blot hybridization analysis. The concentrations of DA, 5-hydroxytryptamine (5-HT), and their acid metabolites were determined by HPLC with electrochemical detection. The postnatal development of the PPE-derived peptide ME and the PPT-derived peptide SP closely paralleled the appearance of the respective mRNAs coding for these peptides. The dopaminergic lesion with 6-OHDA led to a marked depletion of DA and its metabolites but produced an increase in content of 5-HT and its metabolite in the striatum. The lesion did not affect the ME and PPE mRNA levels in the striatum up to 25 days but increased the levels at 35 days. In contrast, a decreased developmental expression in SP and PPT mRNA was observed throughout the observation period. The lesion failed to influence the development of the mRNA coding for the structural protein beta-actin. The results indicate that the normal development of enkephalin, tachykinin, and 5-HT systems of the striatum is dependent on the availability of DA, the integrity of dopaminergic neurons, or both. The studies provide evidence for an interrelationship and interdependence between the development of neuro-transmitter and neuropeptide systems. It is suggested that an early developmental abnormality in the DA system could permanently alter the neuropeptide systems, which in turn could influence the progression and expression of the DA-deficiency state parkinsonism, Lesch-Nyhan disease, or both. C1 WASHINGTON UNIV, SCH MED, DEPT ANAT & NEUROBIOL, ST LOUIS, MO 63110 USA. UNIV N CAROLINA, SCH MED, DEPT PSYCHIAT, BRAIN & DEV RES CTR, CHAPEL HILL, NC 27514 USA. UNIV N CAROLINA, SCH MED, DEPT PHARMACOL, CHAPEL HILL, NC 27514 USA. UNIV N CAROLINA, SCH MED, DEPT ANESTHESIOL, CHAPEL HILL, NC 27514 USA. NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, RES TRIANGLE PK, NC 27709 USA. RP INDIANA UNIV, SCH MED, NW CTR MED EDUC, DEPT PHARMACOL & TOXICOL, 3400 BROADWAY, GARY, IN 46408 USA. FU NCRR NIH HHS [S07RR5371]; NINDS NIH HHS [NS 26063, NS 21937] NR 75 TC 31 Z9 31 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1991 VL 56 IS 5 BP 1499 EP 1508 DI 10.1111/j.1471-4159.1991.tb02044.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA FH035 UT WOS:A1991FH03500007 PM 1707436 ER PT J AU PALOMBO, E PORRINO, LJ CRANE, AM BANKIEWICZ, KS KOPIN, IJ SOKOLOFF, L AF PALOMBO, E PORRINO, LJ CRANE, AM BANKIEWICZ, KS KOPIN, IJ SOKOLOFF, L TI CEREBRAL METABOLIC EFFECTS OF MONOAMINE-OXIDASE INHIBITION IN NORMAL AND 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE ACUTELY TREATED MONKEYS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PARGYLINE; ENERGY METABOLISM; BRAIN; LOCUS COERULEUS; SUBSTANTIA NIGRA; INFERIOR OLIVE ID GLUCOSE-UTILIZATION; DOPAMINERGIC-NEURONS; SUBSTANTIA NIGRA; CHRONIC PARKINSONISM; RAT; MPTP; BRAIN; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; NEUROTOXICITY; PARGYLINE AB The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces dopaminergic cell death in the substantia nigra pars compacta (SNpc) and clinical parkinsonism in humans and experimental animals. Pretreatment with monoamine oxidase inhibitors prevents this cell death and associated parkinsonism by blocking the oxidation of MPTP to a toxic intermediate. The 2-deoxyglucose method was used to study the acute effects of MPTP in the monkey brain and the effects of monoamine oxidase inhibition on local cerebral glucose utilization in both normal and MPTP-treated monkeys. MPTP administration alone caused a major increase in glucose utilization in the SNpc and smaller increases in some subnuclei within the ventral tegmental area in which eventual dopaminergic cell loss also occurs. Pretreatment with pargyline abolished these metabolic increases, a finding suggesting both that the oxidized product of MPTP generates the metabolic increases and that the increased glucose consumption may contribute to cell toxicity. On the other hand, in most cortical, thalamic, striatal, brainstem, and cerebellar areas MPTP alone caused reductions in glucose utilization, and pargyline failed to prevent these effects. Pargyline alone depressed metabolism in the locus coeruleus and a few other monoaminergic structures. C1 NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIDA,BETHESDA,MD. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NR 43 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1991 VL 56 IS 5 BP 1639 EP 1646 DI 10.1111/j.1471-4159.1991.tb02062.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA FH035 UT WOS:A1991FH03500025 PM 2013759 ER PT J AU HITRI, A VENABLE, D NGUYEN, HQ CASANOVA, MF KLEINMAN, JE WYATT, RJ AF HITRI, A VENABLE, D NGUYEN, HQ CASANOVA, MF KLEINMAN, JE WYATT, RJ TI CHARACTERISTICS OF [H-3] GBR-12935 BINDING IN THE HUMAN AND RAT FRONTAL-CORTEX SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE DOPAMINE TRANSPORTER; FRONTAL CORTEX; [H-3]GBR-12935; HUMAN BRAIN; SODIUM DEPENDENCY ID DOPAMINE UPTAKE SITES; STRIATAL MEMBRANES; TRANSPORT COMPLEX; MAZINDOL BINDING; UPTAKE INHIBITOR; COCAINE BINDING; HUMAN-BRAIN; RADIOLIGAND; INVIVO; EFFLUX AB Binding characteristics of the selective dopamine uptake inhibitor [H-3]GBR 12935 have been described for the striatum but not for the frontal cortex. We have developed assay conditions for quantifying [H-3]GBR 12935 binding in the frontal cortex. In both the rat and human frontal cortex, the assay required four times more tissue (8 mg/ml) than in the striatum (2 mg/ml). [H-3]GBR 12935 binding in the frontal is complex, as it involves multiple binding sites. The high-affinity binding site is sodium dependent and is inhibited by sodium. In human but not in rat frontal cortex, addition of K+ reversed the sodium inhibition. The pharmacological profile of the high-affinity [H-3]GBR 12935 binding site is consistent with that of the dopamine transporter, because drugs with the most selective dopamine reuptake blocking activities are the most potent displacers of [H-3]GBR 12935 binding. There is a positive correlation between the rat and human inhibitory constants, a finding indicating that there are similar pharmacological profiles across at least these two species. Rats with a 6-hydroxydopamine lesion had a 47% decrease in number of [H-3]GBR 12935 binding sites, a result indicating that at least a portion of these sites had been on presynaptic dopamine terminals. C1 NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. MED COLL GEORGIA,DEPT PSYCHIAT,AUGUSTA,GA 30912. NR 31 TC 34 Z9 36 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1991 VL 56 IS 5 BP 1663 EP 1672 DI 10.1111/j.1471-4159.1991.tb02065.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA FH035 UT WOS:A1991FH03500028 PM 1901595 ER PT J AU MIES, G CRUZ, N SOKOLOFF, L AF MIES, G CRUZ, N SOKOLOFF, L TI COMPARISON OF FREEZE-BLOWING AND FUNNEL-FREEZING OF RAT-BRAIN FOR THE MEASUREMENT OF CEREBRAL GLUCOSE-CONCENTRATION INVIVO SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE RAT; BRAIN; FUNNEL-FREEZING; FREEZE-BLOWING; PLASMA GLUCOSE CLAMP AB The efficacy of funnel-freezing of rat brain to inactivate metabolic processes and preserve in vivo tissue glucose concentration was validated by comparing the results obtained by funnel-freezing with those obtained with freeze-blowing of brain. The arterial plasma glucose level was clamped at 9 mM in halothane-anesthetized rats to produce identical glucose levels in brain tissue prior to freeze fixation. In funnel-frozen and freeze-blown brains, tissue glucose concentrations were 2.47 +/- 0.05 and 2.47 +/- 0.06-mu-mol/g (means +/- SEM), respectively. Lactate levels in funnel-frozen brains were slightly but significantly higher than those in freeze-blown brains, i.e., 1.56 +/- 0.05-mu-mol/g versus 1.30 +/- 0.05-mu-mol/g (means +/- SEM; p < 0.05). Regional analysis in funnel-frozen brains revealed that glucose concentrations in superficial and basal brain areas remained approximately equal at 2.30 +/- 0.1-mu-mol/g and 2.31 +/- 0.09-mu-mol/g (means +/- SEM), respectively. Our findings indicate that in the anesthetized rat, funnel-freezing of brain is suitable for the measurement of regional in vivo glucose concentrations. C1 MAX PLANCK INST NEUROL RES,DEPT EXPTL NEUROL,COLOGNE,GERMANY. RP MIES, G (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 9 TC 14 Z9 14 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1991 VL 56 IS 5 BP 1673 EP 1676 DI 10.1111/j.1471-4159.1991.tb02066.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA FH035 UT WOS:A1991FH03500029 PM 2013760 ER PT J AU KATSETOS, CD FRANKFURTER, A CHRISTAKOS, S TSOKOS, M VALSAMIS, MP MAKER, HS WOLFE, D DIROCCO, A BERGLAND, RM URICH, H AF KATSETOS, CD FRANKFURTER, A CHRISTAKOS, S TSOKOS, M VALSAMIS, MP MAKER, HS WOLFE, D DIROCCO, A BERGLAND, RM URICH, H TI DIFFERENTIAL EXPRESSION OF NEURONAL CLASS-III BETA-TUBULIN ISOTYPE AND CALBINDIN D28K IN THE DEVELOPING HUMAN CEREBELLAR CORTEX AND CEREBELLAR NEUROBLASTOMAS (MEDULLOBLASTOMAS) SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 BETH ISRAEL MED CTR,NEW YORK,NY 10003. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. NCI,BETHESDA,MD 20892. HAHNEMANN UNIV,PHILADELPHIA,PA 19102. NEW YORK MED COLL,VALHALLA,NY 10595. NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1991 VL 50 IS 3 BP 293 EP 293 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA FK140 UT WOS:A1991FK14000021 ER PT J AU KITTUR, S ADLER, W MARTIN, G KLEIN, H WEEKS, B MARKESBERY, W AF KITTUR, S ADLER, W MARTIN, G KLEIN, H WEEKS, B MARKESBERY, W TI ALZHEIMERS-DISEASE BRAIN EXTRACT CAUSES STIMULATION OF BRANCHING OF NEURONAL CELLS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NIA,BALTIMORE,MD 21224. UNIV KENTUCKY,LEXINGTON,KY 40506. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1991 VL 50 IS 3 BP 304 EP 304 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA FK140 UT WOS:A1991FK14000055 ER PT J AU ARIMA, K MURAYAMA, S INOSE, T AF ARIMA, K MURAYAMA, S INOSE, T TI IMMUNOCYTOCHEMICAL AND ULTRASTRUCTURAL STUDIES OF OLIGODENDROGLIAL AND NEURONAL CYTOPLASMIC INCLUSIONS IN MULTIPLE SYSTEM ATROPHY SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. UNIV N CAROLINA,CHAPEL HILL,NC 27514. NATL CTR NEUROL & PSYCHIAT,TOKYO,JAPAN. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1991 VL 50 IS 3 BP 307 EP 307 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA FK140 UT WOS:A1991FK14000063 ER PT J AU HENKEN, DB MARTIN, JR AF HENKEN, DB MARTIN, JR TI SUBSTANCE-P AND CALCITONIN GENE-RELATED PEPTIDE IN POPULATIONS OF MOUSE DORSAL-ROOT GANGLION NEURONS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIH,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1991 VL 50 IS 3 BP 333 EP 333 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA FK140 UT WOS:A1991FK14000141 ER PT J AU STONER, GL RYSCHKEWITSCH, CF AF STONER, GL RYSCHKEWITSCH, CF TI EVIDENCE FOR JC VIRUS IN 2 PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) BRAINS PREVIOUSLY REPORTED TO BE INFECTED WITH SV40 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1991 VL 50 IS 3 BP 342 EP 342 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA FK140 UT WOS:A1991FK14000168 ER PT J AU RESSETAR, HG PRAKASH, O FRISQUE, R WEBSTER, H STONER, G AF RESSETAR, HG PRAKASH, O FRISQUE, R WEBSTER, H STONER, G TI PATHOLOGY IN TRANSGENIC MICE CARRYING SV40-JC HYBRID VIRAL-DNA SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 PENN STATE UNIV,UNIVERSITY PK,PA 16802. NIH,BETHESDA,MD 20892. ALTON OCHSNER MED FDN & OCHSNER CLIN,NEW ORLEANS,LA 70121. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1991 VL 50 IS 3 BP 370 EP 370 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA FK140 UT WOS:A1991FK14000249 ER PT J AU SARIS, SC BLASBERG, RG CARSON, RE DEVROOM, HL LUTZ, R DEDRICK, RL PETTIGREW, K CHANG, R DOPPMAN, J WRIGHT, DC HERSCOVITCH, P OLDFIELD, EH AF SARIS, SC BLASBERG, RG CARSON, RE DEVROOM, HL LUTZ, R DEDRICK, RL PETTIGREW, K CHANG, R DOPPMAN, J WRIGHT, DC HERSCOVITCH, P OLDFIELD, EH TI INTRAVASCULAR STREAMING DURING CAROTID-ARTERY INFUSIONS - DEMONSTRATION IN HUMANS AND REDUCTION USING DIASTOLE-PHASED PULSATILE ADMINISTRATION SO JOURNAL OF NEUROSURGERY LA English DT Article DE DRUG DELIVERY; CHEMOTHERAPY; CAROTID ARTERY; BRAIN TUMOR; BRAIN INJURY; POSITRON EMISSION TOMOGRAPHY ID 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA BCNU; MALIGNANT GLIOMAS; DRUG INFUSION; CHEMOTHERAPY; LIMITATIONS; CISPLATIN; DELIVERY; FLOW; PET AB Intra-arterial carotid artery chemotherapy for malignant gliomas is limited by focal injuries to the eye and brain which may be caused by poor mixing of the drug with blood at the infusion site. This inadequate mixing can be eliminated in animal models with diastole-phased pulsatile infusion (DPPI) which creates 1-ml/sec spurts during the slow blood flow phase of diastole. Before treatment with intracarotid cisplatin, 10 patients with malignant gliomas were studied to determine whether intravascular streaming occurs after intracartid infusion in humans, and if so, if it is reduced with DPPI. Regional cerebral blood flow (rCBF) studies were performed by intravenous injection of H2(15)O and positron emission tomography. This was followed by supraor infraophthalmic internal carotid artery (ICA) injections of H2(15)O with either continuous infusion or DPPI. Local H2(15)O concentration in the brain was determined and the images of radiotracer distribution in the continuous infusion and DPPI studies were compared to the rCBF images. Intravascular streaming of the infusate was identified by a heterogeneous distribution of the infused H2(15)O in brain compared to rCBF. Extensive and variable intravascular streaming occurred in three patients who received infusions into the supraophthalmic segment of the ICA. Some brain areas received up to 11 times the expected radiotracer delivery, while other regions received as little as one-tenth. This streaming pattern was markedly reduced or eliminated by DPPI. In the five patients who received infraophthalmic infusions, a minimally heterogeneous distribution of the infusate was detected. The authors conclude that extensive intravascular streaming accompanies supraophtalmic ICA infusions in patients. The magnitude of streaming can be substantially reduced or eliminated with DPPI. Those who perform intra-arterial infusion should consider using DPPI to assure uniform drug delivery to brain. C1 NINCDS,SURG NEUROL BRANCH,CLIN NEUROSURG SECT,BLDG 10,ROOM 5D37,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,POSITRON EMISS TOMOG SECT,BETHESDA,MD 20892. NIMH,THEORET STAT & MATH BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT RADIOL,WASHINGTON,DC 20007. DIV RES SERV,BIOMED ENGN & INSTRUMENTAT BRANCH,BETHESDA,MD. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 22 TC 44 Z9 45 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1991 VL 74 IS 5 BP 763 EP 772 DI 10.3171/jns.1991.74.5.0763 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA FH457 UT WOS:A1991FH45700013 PM 1849555 ER PT J AU CHIUEH, CC AF CHIUEH, CC TI STABILITY OF 6-(F-18)FLUORODOPA PREPARATIONS - REPLY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter ID PET RP CHIUEH, CC (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1991 VL 32 IS 5 BP 894 EP 895 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FL183 UT WOS:A1991FL18300043 ER PT J AU DUNN, BB KIESEWETTER, DO AF DUNN, BB KIESEWETTER, DO TI STABILITY OF 6-[F-18]FLUORODOPA PREPARATIONS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter ID PET RP DUNN, BB (reprint author), NIH,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1991 VL 32 IS 5 BP 894 EP 894 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FL183 UT WOS:A1991FL18300042 PM 1902510 ER PT J AU ABRAMS, SA SIDBURY, JB MUENZER, J ESTEBAN, NV VIEIRA, NE YERGEY, AL AF ABRAMS, SA SIDBURY, JB MUENZER, J ESTEBAN, NV VIEIRA, NE YERGEY, AL TI STABLE ISOTOPIC MEASUREMENT OF ENDOGENOUS FECAL CALCIUM EXCRETION IN CHILDREN SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE FECAL CALCIUM EXCRETION; ISOTOPE; URINARY CALCIUM, EXCRETION ID ABSORPTION; METABOLISM; ADOLESCENTS; BALANCE; INFANTS; TRACERS AB Using a stable isotopic technique in which Ca-42 was administered via a bolus injection, we measured endogenous fecal calcium excretion, V(f), in five healthy children, aged 3-14 years. The V(f) averaged 1.4 +/- 0.4 mg/kg/day, and was lower than urinary Ca excretion (V(u)) in four of the five children. These results for V(f) are consistent with previously reported results for V(f) in healthy adults and much lower than those reported in premature infants. These results may be useful in understanding developmental changes in Ca metabolism and in interpreting dual tracer Ca isotope studies in children. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT PEDIAT,ANN ARBOR,MI 48109. RP ABRAMS, SA (reprint author), NICHHD,THEORET & PHYSIOL BIOL LAB,9000 ROCKVILLE PIKE,BLDG 10-6C-101,BETHESDA,MD 20892, USA. OI Abrams, Steven/0000-0003-4972-9233 NR 31 TC 46 Z9 46 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 1991 VL 12 IS 4 BP 469 EP 473 DI 10.1097/00005176-199105000-00010 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA FN783 UT WOS:A1991FN78300010 PM 1865281 ER PT J AU ROILIDES, E CLERICI, M DEPALMA, L RUBIN, M PIZZO, PA SHEARER, GM AF ROILIDES, E CLERICI, M DEPALMA, L RUBIN, M PIZZO, PA SHEARER, GM TI HELPER T-CELL RESPONSES IN CHILDREN INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF PEDIATRICS LA English DT Article ID SEROLOGIC MARKERS; PROGNOSTIC VALUE; IMMUNE FUNCTION; AIDS; ANTIBODIES; ANTIGENS; NUMBERS; HIV AB Helper T-cell function was evaluated in 34 children infected with human immunodeficiency virus type 1, by assessing interleukin-2 production after stimulation of peripheral blood mononuclear cells with recall antigens (influenza virus, tetanus toxoid), allogeneic HLA, and phytohemagglutinin. In addition, helper T-cell function was correlated retrospectively with the incidence of opportunistic and bacterial infections. Four patterns of helper T-cell function were observed: (1) 7 (21%) of the 34 children responded to all stimuli, (2) 7 (21%) of them responded to alloantigens and phytohemagglutinin but not to recall antigens, (3) 7 (21%) responded to phytohemagglutinin but not to recall antigens or alloantigens, and (4) 13 (37%) did not respond to any of these stimuli. There were no significant differences related to different routes of acquisition among patients. Patients with functional helper T-cell defects had a history of more opportunistic (p = 0.03) and bacterial (p < 0.001) infections than did patients with intact helper T-cell function. Thus distinct patterns of helper T-cell dysfunction exist in children infected with human immunodeficiency virus type 1 and correlate with higher frequency of infections. Comparisons of in vitro helper T-cell responses to these stimuli may be useful for detecting early functional helper T-cell defects and for monitoring progression of disease. C1 NCI, DIV CANC TREATMENT, PEDIAT ONCOL BRANCH, INFECT DIS SECT, BETHESDA, MD 20892 USA. NCI, DIV CANC BIOL, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. NCI, CTR DIAG, BETHESDA, MD 20892 USA. CHILDRENS NATL MED CTR, WASHINGTON, DC USA. GEORGE WASHINGTON UNIV, SCH MED, WASHINGTON, DC 20052 USA. NR 23 TC 67 Z9 67 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 MAY PY 1991 VL 118 IS 5 BP 724 EP 730 DI 10.1016/S0022-3476(05)80033-2 PG 7 WC Pediatrics SC Pediatrics GA FK458 UT WOS:A1991FK45800011 PM 1673468 ER PT J AU LEVY, HL LOBBREGT, D KOCH, R DELACRUZ, F AF LEVY, HL LOBBREGT, D KOCH, R DELACRUZ, F TI PATERNAL PHENYLKETONURIA SO JOURNAL OF PEDIATRICS LA English DT Note ID MATERNAL PHENYLKETONURIA; HYPERPHENYLALANINEMIA C1 HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02115 USA. MASSACHUSETTS DEPT PUBL HLTH, STATE LAB INST, NEWBORN SCREENING PROGRAM, BOSTON, MA 02130 USA. CHILDRENS HOSP LOS ANGELES, DIV MED GENET, LOS ANGELES, CA USA. NICHHD, BETHESDA, MD 20892 USA. RP LEVY, HL (reprint author), CHILDRENS HOSP MED CTR, DIV GENET, BIOCHEM GENET UNIT, GARDNER 648, 300 LONGWOOD AVE, BOSTON, MA 02115 USA. FU NICHD NIH HHS [N01-HD-4-2809] NR 15 TC 2 Z9 2 U1 1 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 MAY PY 1991 VL 118 IS 5 BP 741 EP 743 DI 10.1016/S0022-3476(05)80038-1 PG 3 WC Pediatrics SC Pediatrics GA FK458 UT WOS:A1991FK45800016 PM 2019930 ER PT J AU MCCANN, DJ SU, TP AF MCCANN, DJ SU, TP TI SOLUBILIZATION AND CHARACTERIZATION OF HALOPERIDOL-SENSITIVE (+)-[H-3]SKF-10,047 BINDING-SITES (SIGMA SITES) FROM RAT-LIVER MEMBRANES SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GUINEA-PIG BRAIN; HIGH-AFFINITY; RECEPTOR; PHENCYCLIDINE; SYSTEMS; LIGAND AB The zwitterionic detergent 3-[(3-cholamidopropyl)dimethylamino]-1-propanesulfonate (CHAPS) produced optimal solubilization of (+)-[H-3]SKF-10,047 binding sites from rat liver membranes at a concentration of 0.2%, well below the critical micellular concentration of the detergent. The pharmacological selectivity of the liver (+)-[H-3]SKF-10,047 binding sites corresponds to that of sigma sites from rat and guinea pig brain. When the affinities of 18 different drugs at (+)-[H-3]SKF-10,047 binding sites in membranes and solubilized preparations were compared, a correlation coefficient of 0.99 and a slope of 1.03 were obtained, indicating that the pharmacological selectivity of rat liver sigma sites is retained after solubilization. In addition, the binding of 20 nM [H-3]progesterone to solubilized rat liver preparations was found to exhibit a pharmacological selectivity appropriate for sigma sites. A stimulatory effect of phenytoin on (+)-[H-3]SKF-10,047 binding to sigma sites persisted after solubilization. When the solubilized preparation was subjected to molecular sizing chromatography, a single peak exhibiting specific (+)-[H-3]SKF-10,047 binding was obtained. The binding activity of this peak was stimulated symmetrically when assays were performed in the presence of 300-mu-M phenytoin. The molecular weight of the CHAPS-solubilized sigma site complex was estimated to be 450,000 daltons. After solubilization with CHAPS, rat liver sigma sites were enriched to 12 pmol/mg of protein. The present results demonstrate a successful solubilization of sigma sites from rat liver membranes and provide direct evidence that the gonadal steroid progesterone binds to sigma sites. The results also suggest that the anticonvulsant phenytoin binds to an associated allosteric site on the sigma site complex. RP MCCANN, DJ (reprint author), NIDA,ADDICT RES CTR,NEUROCHEM UNIT,NEUROPHARMACOL LAB,POB 5180,BALTIMORE,MD 21224, USA. NR 31 TC 67 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 MAY PY 1991 VL 257 IS 2 BP 547 EP 554 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FM161 UT WOS:A1991FM16100002 PM 1851829 ER PT J AU WITKIN, JM NICHOLS, DE TERRY, P KATZ, JL AF WITKIN, JM NICHOLS, DE TERRY, P KATZ, JL TI BEHAVIORAL-EFFECTS OF SELECTIVE DOPAMINERGIC COMPOUNDS IN RATS DISCRIMINATING COCAINE INJECTIONS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID STIMULUS PROPERTIES; ANTAGONIST SCH-23390; NONHUMAN-PRIMATES; D-1 ANTAGONIST; RHESUS-MONKEYS; RECEPTOR; AGONIST; D1; DRUGS; NOREPINEPHRINE AB The involvement of dopamine receptor subtypes in the discriminative stimulus effects of cocaine was evaluated by the ability of a series of compounds selective for D1 or D2 dopamine receptors to produce discriminative stimulus effects comparable to cocaine. Male, Sprague-Dawley rats were trained to discriminate 10 mg/kg of cocaine HCI from saline in a two-lever discrimination procedure. Inhibitors of catecholamine and serotonin reuptake (GBR 12909, WIN 35,428 and mazindol), d-amphetamine, and the nonselective dopamine agonist, apomorphine, produced dose-dependent increases in cocaine-appropriate responding and fully substituted for cocaine. Cocaine methiodide, a charged, quaternary cocaine analog, did not substitute for cocaine. Neither pentobarbital, haloperidol nor SCH 23390 produced cocaine-like behavioral activity. Both D1- and D2-selective agonists with diverse structures partially substituted for cocaine, producing from 40 to 80% cocaine-appropriate responses. The D1 agonists studied were SKF 38393 and stereoisomers, SKF 75670 and CY 208-243. Dihydrexidine, a full D1 agonist for induction of adenylate cyclase activity, also only partially substituted for cocaine. The peripherally acting D1 agonist, fenoldopam, produced predominantly saline-appropriate responding that was unrelated to dose. The D2 agonists tested were pergolide, quinpirole, (-)-NPA, RU 24213, N-0434 and N-0437. The D2 antagonist haloperidol did not block the discriminative stimulus effects of cocaine. In contrast, the D1 antagonist SCH 23390 reduced the discriminative stimulus effects of cocaine by a maximum of 50%. These results suggest that both D1 and D2 receptors may play a role in the discriminative stimulus effects of cocaine but that stimulation of either dopamine receptor subtype alone is not sufficient. RP WITKIN, JM (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,PSYCHOBIOL LAB,DRUG DEV GRP,POB 5180,BALTIMORE,MD 21224, USA. OI Katz, Jonathan/0000-0002-1068-1159 NR 51 TC 206 Z9 206 U1 2 U2 2 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 MAY PY 1991 VL 257 IS 2 BP 706 EP 713 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FM161 UT WOS:A1991FM16100025 PM 1674533 ER PT J AU ZACZEK, R CULP, S GOLDBERG, H MCCANN, DJ DESOUZA, EB AF ZACZEK, R CULP, S GOLDBERG, H MCCANN, DJ DESOUZA, EB TI INTERACTIONS OF [H-3] AMPHETAMINE WITH RAT-BRAIN SYNAPTOSOMES .1. SATURABLE SEQUESTRATION SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID REPEATED FENFLURAMINE; L-AMPHETAMINE; SEROTONIN; DOPAMINE; RELEASE; NEURONS; BINDING; NOREPINEPHRINE; STEREOISOMERS; TERMINALS AB Previous studies have identified a saturable site of d-[H-3]amphetamine sequestration (AMSEQ) in rat brain synaptosomes. The present study characterized AMSEQ with respect to its subcellular, neuronal and regional distributions, ontogenetic development, pharmacological specificity and factors required for its maintenance. Although AMSEQ was reduced when assays were performed in Krebs' buffer incubated at 37-degrees-C as compared to assays performed in isotonic Tris-sucrose buffer incubated at room temperature, the pharmacological profiles of AMSEQ were virtually identical under both conditions. AMSEQ was negligible in tissues outside the central nervous system, enriched in synaptosomes and partially reduced by striatal kainic acid lesion, indicating neuronal localization. The distribution of AMSEQ in the central nervous system was heterogenous. Highest levels were present in hypothalamus with progressively lower levels noted in parietal cortex, frontal cortex, striatum, thalamus, hippocampus, midbrain, cerebellum, pons-medulla and spinal cord. With regard to its ontogeny, AMSEQ increased early in neonatal life, reaching adult levels by postnatal day 14. Although the effects of amphetamine to abolish the transynaptosomal pH gradient suggests a possible role for this gradient in the maintenance of AMSEQ, the pharmacological profile of AMSEQ indicates that other factors are involved. An interaction with an intrasynaptosomal acid, such as N-acetylaspartate, may account for AMSEQ maintenance. AMSEQ did not possess a stereospecific preference for either d- (IC50 = 177-mu-M) or l-amphetamine (IC50 = 173-mu-M). However, the pharmacological profile of AMSEQ indicated structural specificity with antidepressants being relatively potent inhibitors. The saturation analysis and pharmacological characteristics of AMSEQ (i.e., low affinity and lack of stereospecificity) suggest that AMSEQ may be related to high dose, nonstereospecific effects of amphetamine, such as stereotype in rats and psychosis in humans. The relative high potency of antidepressants in inhibiting AMSEQ suggests the importance of this phenomenon in the therapeutic effects of these drugs. Furthermore, the link between antidepressants and AMSEQ may provide insight into the comorbidity of major depression and drug abuse. C1 NIDA, ADDICT RES CTR, NEUROSCI BRANCH, BALTIMORE, MD USA. RP DUPONT MERCK PHARMACEUT CO, EXPTL STN, E400, POB 80400, WILMINGTON, DE 19880 USA. NR 39 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1991 VL 257 IS 2 BP 820 EP 829 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FM161 UT WOS:A1991FM16100040 PM 1903445 ER PT J AU ZACZEK, R CULP, S DESOUZA, EB AF ZACZEK, R CULP, S DESOUZA, EB TI INTERACTIONS OF [H-3] AMPHETAMINE WITH RAT-BRAIN SYNAPTOSOMES .2. ACTIVE-TRANSPORT SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MAZINDOL BINDING; DOPAMINE UPTAKE; AMPHETAMINE; RELEASE; NOREPINEPHRINE; STRIATUM AB The accumulation of 5 nM d-[H-3]amphetamine (d-[H-3]AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-[H-3]AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-[H-3]AMPH transport (AMT) saturation isotherms indicated an apparent K(m) of 97 nM and a V(max) of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of [H-3] dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain region with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its l-isomer (IC50 = 466 nM). DA (IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM: methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9-mu-M). There was a highly significant (P < .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-[H-3]AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration, are also discussed. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD. NR 18 TC 70 Z9 71 U1 0 U2 2 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 MAY PY 1991 VL 257 IS 2 BP 830 EP 835 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FM161 UT WOS:A1991FM16100041 PM 1903446 ER PT J AU DUBELL, WH BOYETT, MR SPURGEON, HA TALO, A STERN, MD LAKATTA, EG AF DUBELL, WH BOYETT, MR SPURGEON, HA TALO, A STERN, MD LAKATTA, EG TI THE CYTOSOLIC CALCIUM TRANSIENT MODULATES THE ACTION-POTENTIAL OF RAT VENTRICULAR MYOCYTES SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CARDIAC PURKINJE-FIBERS; NA-CA-EXCHANGE; GUINEA-PIG; SARCOPLASMIC-RETICULUM; INWARD CURRENT; OUTWARD CURRENT; CELLS; MUSCLE; RYANODINE; CONTRACTION AB 1. The modulation of the action potential by the cytosolic Ca2+ (Ca(i)2+) transient was studied in single isolated rat ventricular myocytes loaded with the acetoxymethyl ester form of the Ca2+-sensitive fluorescent dye Indo-1. Stimulation following rest and exposure to ryanodine were used to change the amount of Ca2+ released from the sarcoplasmic reticulum and thus the size of the Ca(i)2+ transient. The Ca(i)2+ transient was measured as the change, upon stimulation, in the ratio of Indo-1 fluorescence at 410 nm to that at 490 nm (410/490) and action potentials or membrane currents were recorded using patch-type microelectrodes. 2. When stimulation was initiated following rest, the magnitude of the Ca(i)2+ transient decreased in a beat-dependent manner until a steady state was reached. The negative staircase in the Ca(i)2+ transient was accompanied by a similar beat-dependent decrease in the duration of the action potential, manifested primarily as a gradual loss of the action potential plateau (almost-equal-to -45 mV). A slow terminal phase of repolarization of a few millivolts in amplitude was found to parallel the terminal decay of the Ca(i)2+ transient. 3. The terminal portion of phase-plane loops of membrane potential (V(m)) vs. Indo-1 ratio from all of the beats of a stimulus train followed a common linear trajectory even though the individual beats differed markedly in the duration and amplitude of the action potential and Ca(i)2+ transient. 4. When the stimulation dependence of the Ca(i)2+ transient was titrated away with submaximal exposure to ryanodine, the stimulation-dependent changes in the action potential plateau and terminal phase of repolarization were also eliminated. The same effect was noted in cells which, fortuitously, did not show a staircase in the Ca(i)2+ transient following a period of rest. 5. When action potentials were triggered immediately following spontaneous release of Ca2+ from the sarcoplasmic reticulum, which results in a small depolarization at the resting potential, phase-plane loops (V(m) vs. Indo-1 ratio) of the spontaneous events followed the same linear trajectory as the terminal phase of repolarization in the loops of the stimulated beats. 6. Following repolarization from brief voltage clamp pulses (to minimize time-and voltage-dependent currents associated with depolarization), an inward current was observed that rose and fell in phase with the Ca(i)2+ transient. This current was present at -70 mV, near the resting potential, and at -40 mV, a potential relevant to the plateau of the action potential. During trains of 50 ms voltage clamp pulses (-70 to 0 mV) following rest, this inward current showed a negative staircase paralleling that of the Ca(i)2+ transient. Phase-plane plots (inward current vs. Indo-1 ratio) from each beat were linear and plots from successive beats in a voltage clamp train superimposed on this line. This relationship is analogous to that seen in phase-plane loops of action potential trains during the terminal phase of repolarization. 7. Application of LiCl to the surface of a cell during a steady-state train of stimulated action potentials resulted in a decrease in the duration of the subsequent action potential as the plateau potential and the magnitude of the terminal phase of repolarization were decreased. 8. The results show that the waveform of the rat ventricular action potential is partially dependent on currents that are mediated by the Ca(i)2+ transient. This effect becomes apparent after the time- and voltage-dependent currents responsible for the upstroke of the action potential are inactivated. The Ca(i)2+-dependent current, at least a portion of which can be attributed to electrogenic Na+-Ca2+ exchange, regulates the action potential duration. C1 UNIV LEEDS,DEPT PHYSIOL,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. UNIV TURKU,DEPT BIOL,SF-20500 TURKU 60,FINLAND. RP DUBELL, WH (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224, USA. FU Wellcome Trust NR 44 TC 54 Z9 54 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY PY 1991 VL 436 BP 347 EP 369 PG 23 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA FM063 UT WOS:A1991FM06300020 PM 2061836 ER PT J AU DIAMOND, LS CUNNICK, CC AF DIAMOND, LS CUNNICK, CC TI A SERUM-FREE, PARTLY DEFINED MEDIUM, PDM-805, FOR AXENIC CULTIVATION OF ENTAMOEBA-HISTOLYTICA SCHAUDINN, 1903 AND OTHER ENTAMOEBA SO JOURNAL OF PROTOZOOLOGY LA English DT Article DE AMMONIUM MOIETY; AXENIC CULTIVATION; CASEIN PEPTONE DIALYSATE; ENTAMOEBA-BARRETI; ENTAMOEBA-INVADENS; ENTAMOEBA-TERRAPINAE; LIPOPROTEIN-CHOLESTEROL SOLUTION; NUTRITION ID GIARDIA-LAMBLIA; CLONAL GROWTH; ATTACHMENT; PROTEIN AB We describe the first serum-free, partly defined medium (PDM-805)for cultivating the human enteric pathogen, Entamoeba histolytica, and the reptilian amebae E. barreti, E. invadens, and E. terrapinae. PDM-805 was developed by the stepwise replacement of yeast extract, bovine serum, and a casein peptone digest in TYI-S-33, a medium widely used for the axenic cultivation of these parasites. The defined components include amino acids, carbohydrates, B vitamins, ascorbic acid, tocopherol, thioctic acid, nucleic acid precursors, trace metals, and phosphate buffers. The undefined components include a highly purified bovine serum albumin, a lipoprotein-cholesterol solution from bovine serum, and a dialyzable, autoclavable, water-soluble growth factor(s) having a molecular weight of less than 3,500 prepared from casein peptone. To date, studies on the growth requirements of E. histolytica, strain 200:NIH, show the following are essential for sustained multiplication of this ameba: iron, glucose, biotin, folic acid, niacinamide, pantothenate, pyridoxal, riboflavin, thiamine, cysteine, an ammonium moiety (in addition to that present in cysteine), bovine serum albumin, lipoprotein-cholesterol, and casein peptone dialysate. RP DIAMOND, LS (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 25 TC 15 Z9 15 U1 0 U2 3 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 0022-3921 J9 J PROTOZOOL PD MAY-JUN PY 1991 VL 38 IS 3 BP 211 EP 216 DI 10.1111/j.1550-7408.1991.tb04430.x PG 6 WC Zoology SC Zoology GA FQ064 UT WOS:A1991FQ06400007 PM 1880759 ER PT J AU NOZAKI, T DVORAK, JA AF NOZAKI, T DVORAK, JA TI TRYPANOSOMA-CRUZI - FLOW CYTOMETRIC ANALYSIS OF DEVELOPMENTAL STAGE DIFFERENCES IN DNA SO JOURNAL OF PROTOZOOLOGY LA English DT Article DE A-T CONTENT; EPIMASTIGOTES; G-C CONTENT; METACYCLOGENESIS; TRYPOMASTIGOTES ID SURFACE; FORMS; PURIFICATION; EXPRESSION; CHROMATIN; STOCKS; BRUCEI; LYSIS; CELL AB Flow cytometry and DNA binding-specific fluorescent reagents were used to compare the total DNA, G-C, and A-T content of the epimastigote and trypomastigote stages of Trypanosoma cruzi stocks. Significant total DNA differences of 2-12% between epimastigotes and trypomastigotes were found in three of six stocks studied. The epimastigote G-C content of five of six stocks was 4-8% higher than trypomastigotes, whereas the trypomastigote A-T content was 2.5-13% higher than the epimastigote A-T content. Although no obvious developmental stage association between total DNA and base composition was found, intrastage associations do exist. These observations were unaffected by nucleoprotein extraction implying that the observed differences between trypomastigotes and epimastigotes are not a consequence of nucleoprotein interference with DNA-binding fluorochromes. The nuclei and kinetoplasts of four T. cruzi stocks were isolated and analyzed. Developmental stage differences in nuclear and kinetoplast DNA are stock-dependent and base composition-dependent; both organelles contribute to the observed differences in DNA of intact cells. We found a nearly linear association between the percentage of total kinetoplast DNA, G-C, and A-T content. During metacyclogenesis, the G-C content decreases by approximately 7% as epimastigotes transform into metacyclic trypomastigotes. The decrease in G-C content precedes changes in morphology or in complement resistance. If the DNA changes are causally connected to developmental stage transformations in T. cruzi remains to be determined. However, our results could facilitate studies of the molecular genetic processes the parasite uses to successfully complete various phases of its life cycle and, consequently, the disease process it evokes. RP NOZAKI, T (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 49 TC 24 Z9 24 U1 0 U2 1 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 0022-3921 J9 J PROTOZOOL PD MAY-JUN PY 1991 VL 38 IS 3 BP 234 EP 243 DI 10.1111/j.1550-7408.1991.tb04435.x PG 10 WC Zoology SC Zoology GA FQ064 UT WOS:A1991FQ06400012 PM 1880761 ER PT J AU WILDT, DE BUSH, M OBRIEN, SJ MURRAY, ND TAYLOR, A GRAVES, JAM AF WILDT, DE BUSH, M OBRIEN, SJ MURRAY, ND TAYLOR, A GRAVES, JAM TI SEMEN CHARACTERISTICS IN FREE-LIVING KOALAS (PHASCOLARCTOS-CINEREUS) SO JOURNAL OF REPRODUCTION AND FERTILITY LA English DT Article DE KOALA; MARSUPIAL; SEMEN; ELECTROEJACULATION; SPERMATOZOA; TESTIS; TESTOSTERONE ID INFERTILITY; LEOPARD; AFRICAN; CHEETAH; TIGER AB Spermic electroejaculates (range in motile sperm/ejaculate, 0.50-122.9 x 10(6); mean +/- s.e.m., 38.6 +/- 4.9) were recovered from 47 of 48 adult koalas captured from 3 wild populations in Australia. Semen was characterized by (i) a high density of globular bodies, which prevented the estimation of sperm motility without dilution; (ii) a brownish colour; and (iii) and acidic pH. Spermatozoa were categorized on the basis of 10 head forms, most cells being a curved or hooked shape. The koala populations differed in sperm concentration and motility ratings, but not in testes size, testosterone production or proportions of spermatozoa with various head shapes. These data confirm that free-living koalas normally produce spermatozoa with a high incidence of structural heterogeneity almost solely confined to the head region; and demonstrate the utility and safety of conventional gamete and endocrine studies, approaches which will be useful for determining the impact of genetic isolation and veneral disease on species fertility. C1 NCI,GENET SECT,FREDERICK,MD 21701. LA TROBE UNIV,DEPT GENET & HUMAN VARIAT,BUNDOORA,VIC 3083,AUSTRALIA. RP WILDT, DE (reprint author), SMITHSONIAN INST,NATL ZOOL PK,WASHINGTON,DC 20008, USA. RI Taylor, Andrea/B-5795-2009; Graves, Jennifer/A-1387-2008 NR 42 TC 24 Z9 24 U1 0 U2 8 PU J REPROD FERTIL INC PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE, ENGLAND CB5 8DT SN 0022-4251 J9 J REPROD FERTIL JI J. Reprod. Fertil. PD MAY PY 1991 VL 92 IS 1 BP 99 EP 107 PG 9 WC Reproductive Biology SC Reproductive Biology GA FN323 UT WOS:A1991FN32300011 PM 2056498 ER PT J AU BLAIR, C AF BLAIR, C TI MATERNO-FOETO-PLACENTAL INTERACTIONS - 21-23 MAY 1990 - SYNOPSIS OF A CONFERENCE SPONSORED BY THE NATIONAL-INSTITUTE-OF-CHILD-HEALTH-AND-HUMAN-DEVELOPMENT, BETHESDA, MD, USA SO JOURNAL OF REPRODUCTION AND FERTILITY LA English DT Editorial Material RP BLAIR, C (reprint author), NICHHD,GENET & TERATOL BRANCH,ROOM EPN 643,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU J REPROD FERTIL INC PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE, ENGLAND CB5 8DT SN 0022-4251 J9 J REPROD FERTIL JI J. Reprod. Fertil. PD MAY PY 1991 VL 92 IS 1 BP 231 EP 233 PG 3 WC Reproductive Biology SC Reproductive Biology GA FN323 UT WOS:A1991FN32300026 ER PT J AU NAHIR, AM HOFFMAN, A LORBER, M KEISER, HR AF NAHIR, AM HOFFMAN, A LORBER, M KEISER, HR TI PRESENCE OF IMMUNOREACTIVE ENDOTHELIN IN SYNOVIAL-FLUID - ANALYSIS OF 22 CASES SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ENDOTHELIN; SYNOVIAL FLUID; RHEUMATOID ARTHRITIS; OSTEOARTHRITIS ID VASCULAR SMOOTH-MUSCLE; MESANGIAL CELLS; EXPRESSION AB The endothelins are a family of recently defined active peptides with a wide range of activities, including the activation of the synthesis of prostaglandins. The concentration of endothelin in inflammatory and noninflammatory synovial fluids (SF) was measured by a sensitive radioimmunoassay. Endothelin-like immunoreactivity was detectable in all SF samples and the mean concentration of endothelin was 2.6 +/- 0.3 pg/ml, more than twice that in normal human plasma. The mean level of endothelin in SF in rheumatoid arthritis was 2.5 +/- 0.4 pg/ml (n = 11), and was not statistically different from either osteoarthritis, 3.0 +/- 0.5 pg/ml (n = 7), or acute inflammatory arthritis, 2.0 +/- 0.4 pg/ml (n = 4). Our data do not support the hypothesis that endothelin plays an important role in the pathogenesis of inflammatory arthritis. C1 TECHNION ISRAEL INST TECHNOL,FAC MED,H SCHUSSHEIM RHEUMATOL RES UNIT,HAIFA,ISRAEL. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. RP NAHIR, AM (reprint author), TECHNION ISRAEL INST TECHNOL,RAMBAM MED CTR,B SHINE DEPT RHEUMATOL,IL-31096 HAIFA,ISRAEL. NR 25 TC 22 Z9 22 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 MAY PY 1991 VL 18 IS 5 BP 678 EP 680 PG 3 WC Rheumatology SC Rheumatology GA FN926 UT WOS:A1991FN92600009 PM 1865412 ER PT J AU LEMLEY, DE FERRANS, VJ FOX, LM SATLER, L CUPPS, TR AF LEMLEY, DE FERRANS, VJ FOX, LM SATLER, L CUPPS, TR TI CARDIAC MANIFESTATIONS OF WEBER-CHRISTIAN DISEASE - REPORT AND REVIEW OF THE LITERATURE SO JOURNAL OF RHEUMATOLOGY LA English DT Review DE WEBER-CHRISTIAN DISEASE; CONGESTIVE HEART FAILURE; CARDIOMYOPATHY, DILATED; CONGESTIVE HEART FAILURE; PERICARDITIS, CONSTRICTIVE ID CARDIOMYOPATHY AB A patient with chronic systemic Weber-Christian disease who was treated with hydroxychloroquine developed cardiac dilatation with congestive heart failure. Endomyocardial biopsy demonstrated myocyte degeneration and interstitial fibrosis, but no typical features of chloroquine induced cardiomyopathy. Clinical symptoms of congestive heart failure also were recognized in 7 of the 11 reported autopsy cases of Weber-Christian disease having cardiac involvement. This involvement can affect the pericardium and the myocardium. C1 GEORGETOWN UNIV,MED CTR,SCH MED,DIV RHEUMATOL,GORMAN BLDG,LOWER LEVEL,3800 RESERVOIR RD NW,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,SCH MED,DIV CARDIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,SCH MED,DIV CARDIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,SCH MED,DIV IMMUNOL & ALLERGY,WASHINGTON,DC 20007. NHLBI,BETHESDA,MD 20892. NR 24 TC 6 Z9 7 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 MAY PY 1991 VL 18 IS 5 BP 756 EP 760 PG 5 WC Rheumatology SC Rheumatology GA FN926 UT WOS:A1991FN92600027 PM 1865427 ER PT J AU ALEXANDER, HR DOHERTY, GM FRAKER, DL BLOCK, MI SWEDENBORG, JE NORTON, JA AF ALEXANDER, HR DOHERTY, GM FRAKER, DL BLOCK, MI SWEDENBORG, JE NORTON, JA TI HUMAN RECOMBINANT INTERLEUKIN-1-ALPHA PROTECTION AGAINST THE LETHALITY OF ENDOTOXIN AND EXPERIMENTAL SEPSIS IN MICE SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 1990 ANNUAL MEETING OF THE ASSOC FOR ACADEMIC SURGERY CY NOV 14-17, 1990 CL HOUSTON, TX SP ASSOC ACAD SURG ID TUMOR NECROSIS FACTOR; BIOLOGICAL-ACTIVITIES; BACTERIAL-INFECTION; LABORATORY MODELS; SEPTIC SHOCK; RESISTANCE; PRETREATMENT; PREVENTION RP ALEXANDER, HR (reprint author), NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892, USA. NR 20 TC 37 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY PY 1991 VL 50 IS 5 BP 421 EP 424 PG 4 WC Surgery SC Surgery GA FM483 UT WOS:A1991FM48300002 PM 2038179 ER PT J AU POGREBNIAK, H MATTHEWS, W MITCHELL, J RUSSO, A SAMUNI, A PASS, H AF POGREBNIAK, H MATTHEWS, W MITCHELL, J RUSSO, A SAMUNI, A PASS, H TI SPIN TRAP PROTECTION FROM TUMOR-NECROSIS-FACTOR CYTOTOXICITY SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 1990 ANNUAL MEETING OF THE ASSOC FOR ACADEMIC SURGERY CY NOV 14-17, 1990 CL HOUSTON, TX SP ASSOC ACAD SURG ID FACTOR-ALPHA; CYTO-TOXICITY; PERITONEAL-MACROPHAGES; INTERFERON-GAMMA; FREE-RADICALS; CACHECTIN; INJURY; CELLS; RATS; NEUTROPHILS C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. RP POGREBNIAK, H (reprint author), NCI,THORAC ONCOL SECT,BETHESDA,MD 20892, USA. NR 36 TC 25 Z9 26 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY PY 1991 VL 50 IS 5 BP 469 EP 474 DI 10.1016/0022-4804(91)90026-I PG 6 WC Surgery SC Surgery GA FM483 UT WOS:A1991FM48300010 PM 2038186 ER PT J AU BARTORELLI, AL LEON, MB ALMAGOR, Y PREVOSTI, LG SWAIN, JA MCINTOSH, CL NEVILLE, RF HOUSE, MD BONNER, RF AF BARTORELLI, AL LEON, MB ALMAGOR, Y PREVOSTI, LG SWAIN, JA MCINTOSH, CL NEVILLE, RF HOUSE, MD BONNER, RF TI INVIVO HUMAN ATHEROSCLEROTIC PLAQUE RECOGNITION BY LASER-EXCITED FLUORESCENCE SPECTROSCOPY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERIES; ANGIOPLASTY; RECANALIZATION; ABLATION; IDENTIFICATION; INVITRO; MEDIA AB Arterial wall perforation and chronic restenosis represent important factors limiting the clinical application of laser angioplasty. Discrimination of normal and atheroscelerotic vessels by laser-excited fluorescence spectroscopy may offer a means of targeting plaque ablation, thereby reducing the frequency of restenosis and transmural perforation. In this study, with use of a 325 nm low power helium-cadmium laser, in vivo endogenous surface fluorescence was excited through a flexible 200-mu-m optical fiber within a 0.018 in. (0.046 cm) guide wire in contact with the intima of 268 vascular interrogation sites from 48 patients either during open heart surgery or during percutaneous catheterization procedures. Fluorescence spectra could be recorded in all patients in bloodless and blood-filled arteries. Endogenous surface fluorescence was analyzed measuring peak intensity, peak position and shape index of the spectra. Compared with normal wall, noncalcified and calcified coronary atheroma showed a 42% (p < 0.001) and a 58% (p < 0.001) decrease of peak intensity, and higher shape index (p < 0.001 and p < 0.01, respectively). In addition, peak position was shifted to longer wavelengths for noncalcified coronary atheroma (p < 0.001). Compared with normal aorta sites, aortic plaques demonstrated a 46% decrease of peak intensity, longer peak position wavelengths (p < 0.05) and a higher shape index (p < 0.001). Using an atheroma detection algorithm, prospective analysis of aorta and coronary spectra showed a specificity of 100% for identifying normal sites and a sensitivity of 73% for recognizing atherosclerotic sites. This study demonstrates that in vivo laser-excited fluorescence spectroscopy of remote human arteries with optical fibers, in either a bloodless or a blood-filled environment, is feasible and accurately discriminates, with use of a real-time computer-controlled algorithm, atherosclerotic from normal vascular tissue. Thus, incorporation of fluorescence spectroscopic feedback control in a laser angioplasty system is feasible and may improve clinical results. C1 NHLBI,DIV RES SERV,SURG BRANCHES,BIOMED ENGN & INSTRUMENTAT BRANCH,BETHESDA,MD 20892. NHLBI,DIV RES SERV,CARDIOL BRANCH,BIOMED ENGN & INSTRUMENTAT BRANCH,BETHESDA,MD 20892. RI Bonner, Robert/C-6783-2015 NR 27 TC 25 Z9 25 U1 0 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 MAY PY 1991 VL 17 IS 6 SU B BP B160 EP B168 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FJ912 UT WOS:A1991FJ91200022 PM 2016474 ER PT J AU SCHATZ, RA GOLDBERG, S LEON, M BAIM, D HIRSHFELD, J CLEMAN, M ELLIS, S TOPOL, E AF SCHATZ, RA GOLDBERG, S LEON, M BAIM, D HIRSHFELD, J CLEMAN, M ELLIS, S TOPOL, E TI CLINICAL-EXPERIENCE WITH THE PALMAZ-SCHATZ CORONARY STENT SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ANGIOPLASTY AB Complications that occurred in 247 patients who underwent successful elective stenting to native coronary arteries with the Palmaz-Schatz balloon expandable stent included subacute thrombosis in 7 patients (2.8%), myocardial infarction in 3 (1.2%), death 3 (1.2%), urgent bypass surgery in 4 (1.6%) and major bleeding events in 24 (9.7%). Angiographic restenosis occurred in 21 (20%) of 103 patients who received a single stent. Subgroup analysis, however, revealed that restenosis of a single stent occurred in 3 (7%) of 45 patients without prior angioplasty compared with 25 (27%) of 91 patients with prior angioplasty. Patients with "suboptimal" angioplasty results (dissection) who received a single stent seemed to have a higher thrombosis rate perioperatively (4 [4%] of 98), but no higher incidence of restenosis (7 [15%] of 46) than that of the total group of patients who received a single stent. Coronary stenting may be a valuable adjunct to coronary angioplasty in carefully selected patients. Complication rates are similar to those of routine angioplasty; however, angiographic restenosis may be reduced in certain subsets of patients. C1 NIH,BETHESDA,MD 20892. BETH ISRAEL HOSP,BOSTON,MA 02215. UNIV PENN,MED CTR,PHILADELPHIA,PA 19104. THOMAS JEFFERSON UNIV,PHILADELPHIA,PA 19107. YALE UNIV,YALE HOSP,NEW HAVEN,CT 06520. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI 48109. RP SCHATZ, RA (reprint author), SCRIPPS CLIN & RES FDN,DIV CARDIOL,10666 N TORREY PINES RD,LA JOLLA,CA 92037, USA. NR 16 TC 73 Z9 74 U1 0 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 MAY PY 1991 VL 17 IS 6 SU B BP B155 EP B159 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FJ912 UT WOS:A1991FJ91200021 PM 2016473 ER PT J AU DUBOSE, TD GOOD, DW HAMM, LL WALL, SM AF DUBOSE, TD GOOD, DW HAMM, LL WALL, SM TI AMMONIUM TRANSPORT IN THE KIDNEY - NEW PHYSIOLOGICAL CONCEPTS AND THEIR CLINICAL IMPLICATIONS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE RENAL TUBULE; AMMONIUM EXCRETION; KIDNEY; ACIDBASE BALANCE; ACIDOSIS ID CHRONIC METABOLIC-ACIDOSIS; MEDULLARY COLLECTING DUCT; TUBULES PERFUSED INVITRO; RAT PROXIMAL TUBULE; THICK ASCENDING LIMB; LUMINAL PH; BICARBONATE TRANSPORT; DISEQUILIBRIUM PH; ANION GAP; SECRETION AB This article is based on a Basic Science Symposium presented at the 23rd Annual Meeting of the American Society of Nephrology. New information on the segmental transport of ammonium by the proximal tubule, the thick ascending limb of Henle's loop, and the collecting duct is integrated into a thesis that NH4+ excretion is controlled by the rate of production, by diffusion of NH3 along gradients established by proton secretion, and by active transport of NH4+. These new concepts are applied to a novel explanation of the pathogenesis of distal renal tubular acidosis. C1 UNIV TEXAS,SCH MED,HOUSTON,TX 77025. UNIV TEXAS,MED BRANCH,MED BRANCH,GALVESTON,TX 77550. WASHINGTON UNIV,ST LOUIS,MO 63130. NIH,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK 01745, DK 30603, DK 38217] NR 49 TC 71 Z9 73 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 1991 VL 1 IS 11 BP 1193 EP 1203 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA FT110 UT WOS:A1991FT11000001 PM 1932632 ER PT J AU PASS, HI EVANS, S MATTHEWS, WA PERRY, R VENZON, D ROTH, JA SMITH, P AF PASS, HI EVANS, S MATTHEWS, WA PERRY, R VENZON, D ROTH, JA SMITH, P TI PHOTODYNAMIC THERAPY OF ONCOGENE-TRANSFORMED CELLS SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 70TH ANNUAL MEETING OF THE AMERICAN ASSOC FOR THORACIC SURGERY CY MAY 07-09, 1990 CL TORONTO, CANADA SP AMER ASSOC THORAC SURG ID LINES AB Photodynamic therapy with dihematoporphyrin ether sensitizes malignant cells to damage by 630 nm light. The in vitro, in vivo photodynamic therapy sensitivity of a cell line transformed by the Kirsten ras oncogene (45342) was studied to establish a new photodynamic therapy model. With the colony formation assay, neither light alone nor dihematoporphyrin ether alone affected 45342 survival. Energy-dependent photodynamic therapy effects were seen in vitro in dihematoporphyrin ether-incubated and light-exposed cells (90% cytotoxicity = 950 joules/m2; 99% cytotoxicity = 1575 joules/m2; p2 < 0.05). Subcutaneous allografts of 45342 were established in nu/nu mice, and ideal route (intravenous or intraperitoneal) of dihematoporphyrin ether delivery, dihematoporphyrin ether tissue kinetics, and in vivo photodynamic therapy effects were examined. Intravenous administration not only gave higher levels of the sensitizer in various tissues, but also was associated with less variation than the intraperitoneal route. Selective dihematoporphyrin ether retention was documented in the tumors at 24 hours after injection compared with other tissues, and photodynamic therapy with 0.3 W/cm2 to a total dose of 150 joules/cm2 led to progressive coagulative tumor necrosis and tumor regression. These studies confirm that transformed, malignant cells are sensitive to photodynamic therapy, and this model may prove useful in future studies to increase efficacy to photodynamic therapy (i.e., with dihematoporphyrin ether delivery by monoclonal antibodies). C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT THORAC SURG,HOUSTON,TX 77030. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,BETHESDA,MD 20892. RP PASS, HI (reprint author), NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 9 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 1991 VL 101 IS 5 BP 795 EP 799 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA FL132 UT WOS:A1991FL13200004 PM 1827169 ER PT J AU JENSEN, JC CHOYKE, PL ROSENFELD, M PASS, HI KEISER, H WHITE, B TRAVIS, W LINEHAN, WM AF JENSEN, JC CHOYKE, PL ROSENFELD, M PASS, HI KEISER, H WHITE, B TRAVIS, W LINEHAN, WM TI A REPORT OF FAMILIAL CAROTID-BODY TUMORS AND MULTIPLE EXTRAADRENAL PHEOCHROMOCYTOMAS SO JOURNAL OF UROLOGY LA English DT Article DE CAROTID BODY TUMOR; PHEOCHROMOCYTOMA; MAGNETIC RESONANCE IMAGING ID RESONANCE AB A case of familial carotid body tumors and multiple extra-adrenal pheochromocytomas is reported. The carotid body tumors, resected previously, were bilateral and associated with 4 intra-abdominal extra-adrenal pheochromocytomas. Magnetic resonance imaging was far superior to computerized tomography and iodine-131-metaiodobenzylguanidine in visualizing the intra-abdominal lesions, and may soon become the imaging technique of choice in the evaluation of patients with suspected pheochromocytoma. C1 NCI,PATHOL BRANCH,BETHESDA,MD 20892. WARREN GRANT MANGUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NIDDKD,CYTOGENET UNIT,BETHESDA,MA. NIH,BETHESDA,MD 20892. RP JENSEN, JC (reprint author), NCI,SURG BRANCH,BETHESDA,MD 20892, USA. NR 11 TC 20 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1991 VL 145 IS 5 BP 1040 EP 1042 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA FJ844 UT WOS:A1991FJ84400031 PM 2016787 ER PT J AU FAKUNDING, JL AF FAKUNDING, JL TI RESEARCH TRAINING IN THE CARDIOVASCULAR SCIENCES SUPPORTED BY THE NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE SO JOURNAL OF VASCULAR SURGERY LA English DT Article RP FAKUNDING, JL (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 1991 VL 13 IS 5 BP 728 EP 729 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA FL780 UT WOS:A1991FL78000025 PM 2027215 ER PT J AU DIDISHEIM, P AF DIDISHEIM, P TI BIOMATERIALS-RELATED PROGRAMS AND INITIATIVES AT THE NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE SO JOURNAL OF VASCULAR SURGERY LA English DT Article RP DIDISHEIM, P (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 1991 VL 13 IS 5 BP 729 EP 729 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA FL780 UT WOS:A1991FL78000026 PM 2027216 ER PT J AU PYLE, SW CHABOT, DJ MILLER, TL SERABYN, SA BESS, JW ARTHUR, LO AF PYLE, SW CHABOT, DJ MILLER, TL SERABYN, SA BESS, JW ARTHUR, LO TI LARGE-SCALE PURIFICATION OF GP70 FROM MOLONEY MURINE LEUKEMIA-VIRUS SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE MOLONEY MURINE LEUKEMIA VIRUS; GLYCOPROTEIN-GP70; PURIFICATION; DETERGENT ID MAJOR ENVELOPE GLYCOPROTEIN; STRUCTURAL PROTEINS; PRECURSOR POLYPEPTIDES; MICE; CELLS; CHROMATOGRAPHY; CLEAVAGE; ANTIGEN; GP69-71; SERA AB The external envelope glycoprotein, gp70, of the Moloney murine leukemia virus was extracted from NIH 3T3 cells utilizing the detergent n-octyl-beta-D-glucopyranoside. The extracted gp70 was sequentially purified utilizing lectin-affinity, anion-exchange, and molecular-exclusion chromatography techniques. Approximately 10 mg of gp70 was purified by this method and shown to be 95% homogeneous, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The presence of purified gp70 from Moloney murine leukemia virus was confirmed by amino acid analysis, amino-terminal sequencing, and immunoreactivity with a monoclonal antibody raised against gp70. The procedure is rapid, utilizes commercially available media, and can be used to purify large amounts of retroviral envelope glycoprotein from virus. RP PYLE, SW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702, USA. RI Bess, Jr., Julian/B-5343-2012 FU PHS HHS [N01-C0-74102] NR 32 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAY PY 1991 VL 32 IS 2-3 BP 303 EP 315 DI 10.1016/0166-0934(91)90060-D PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA FU983 UT WOS:A1991FU98300018 PM 1874922 ER PT J AU MILLER, AD GARCIA, JV VONSUHR, N LYNCH, CM WILSON, C EIDEN, MV AF MILLER, AD GARCIA, JV VONSUHR, N LYNCH, CM WILSON, C EIDEN, MV TI CONSTRUCTION AND PROPERTIES OF RETROVIRUS PACKAGING CELLS BASED ON GIBBON APE LEUKEMIA-VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID EXPRESSION; SEQUENCES; VECTORS; GENE; DNA; ENVELOPE AB We have constructed hybrid retrovirus packaging cell lines that express the gibbon ape luekemia virus env and the Moloney murine leukemia virus gag-pol proteins. These cells were used to produce a retrovirus vector at over 10(6) CFU/ml, with a host range that included rat, hamster, bovine, cat, dog, monkey, and human cells. The gag-pol and env expression plasmids were separately transfected to reduce the potential for helper virus production, which was not observed. The NIH 3T3 mouse cells from which the packaging lines were made are not infectable by gibbon ape leukemia virus; thus, the generation and spread of possible recombinant viruses in the packaging cells is greatly reduced. These simian virus-based packaging cells extend the host range of currently available murine and avian packaging cells and should be useful for efficient gene transfer into higher mammals. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP MILLER, AD (reprint author), FRED HUTCHINSON CANC RES CTR,1124 COLUMBIA WAY,SEATTLE,WA 98104, USA. OI Miller, Dusty/0000-0002-3736-3660 FU NHLBI NIH HHS [HL36444]; NIAID NIH HHS [AI07995] NR 30 TC 522 Z9 528 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1991 VL 65 IS 5 BP 2220 EP 2224 PG 5 WC Virology SC Virology GA FG777 UT WOS:A1991FG77700008 PM 1850008 ER PT J AU COLLINS, PL MOTTET, G AF COLLINS, PL MOTTET, G TI HOMOOLIGOMERIZATION OF THE HEMAGGLUTININ-NEURAMINIDASE GLYCOPROTEIN OF HUMAN PARAINFLUENZA VIRUS TYPE-3 OCCURS BEFORE THE ACQUISITION OF CORRECT INTRAMOLECULAR DISULFIDE BONDS AND MATURE IMMUNOREACTIVITY SO JOURNAL OF VIROLOGY LA English DT Article ID INTRACELLULAR-TRANSPORT; SENDAI VIRUS; INFLUENZA HEMAGGLUTININ; ENDOPLASMIC-RETICULUM; VIRAL GLYCOPROTEIN; CROSS-LINKING; PROTEIN; OLIGOMERIZATION; EXPRESSION; ISOMERASE AB The posttranslational maturation of the hemagglutinin-neuraminidase (HN) glycoprotein of human parainfluenza type 3 virus (PIV3) was investigated in pulse-chase experiments in which folding was monitored by immunoprecipitation with conformation-dependent antibodies and gel electrophoresis under nonreducing conditions and oligomerization was monitored by chemical cross-linking and sedimentation in sucrose gradients. The acquisition of mature immunoreactivity and the formation of correct intramolecular disulfide bonds were concurrent events, with half-times of approximately 10 to 15 min. The finding that newly synthesized HN had little reactivity with postinfection cotton rat serum or with most of the members of a panel of HN-specific monoclonal antibodies indicated that the major epitopes of the PIV3 HN protein are highly conformational in nature. Chemical cross-linking studies indicated that the mature HN protein is present in homooligomers, which are probably tetramers. These findings are consistent with recent observations for the HN protein of Sendai virus (S. D. Thompson, W. G. Laver, K. G. Murti, and A. Portner, J. Virol. 62:4653-4660, 1988; S. Vidal, G. Mottet, D. Kolakofsky, and L. Roux, J. Virol. 63:892-900, 1989). Surprisingly, analysis of pulse-labeled HN protein by sedimentation on sucrose gradients after labeling periods of as little as 2 min indicated that it was present intracellularly only in oligomeric form. The same results were obtained when the labeling period was preceded by a 1.5-h cycloheximide treatment to clear the endoplasmic reticulum of presynthesized HN protein, which indicated that the oligomerization did not involve the incorporation of newly synthesized monomers into partially assembled oligomers. Subsequent chase incubations did not significantly alter the sedimentation profile or stability of the oligomeric forms, suggesting that oligomers detected after short labeling periods were tetramers. Association with cellular proteins did not appear to be responsible for the sedimentation of newly synthesized HN protein as an oligomer. The absence of a detectable monomeric form of intracellular HN protein raised the possibility that oligomerization is cotranslational, and it is possible that the type II membrane orientation of the HN protein might be an important factor in its mode of oligomerization. RP COLLINS, PL (reprint author), NIAID,INFECT DIS LAB,BLDG 7,ROOM 100,BETHESDA,MD 20892, USA. NR 30 TC 33 Z9 33 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 MAY PY 1991 VL 65 IS 5 BP 2362 EP 2371 PG 10 WC Virology SC Virology GA FG777 UT WOS:A1991FG77700027 PM 1707981 ER PT J AU CLAGUE, MJ SCHOCH, C BLUMENTHAL, R AF CLAGUE, MJ SCHOCH, C BLUMENTHAL, R TI DELAY TIME FOR INFLUENZA-VIRUS HEMAGGLUTININ-INDUCED MEMBRANE-FUSION DEPENDS ON HEMAGGLUTININ SURFACE-DENSITY SO JOURNAL OF VIROLOGY LA English DT Article ID PHOSPHOLIPID ASYMMETRY; CELL-SURFACE; FLUORESCENCE; MECHANISM; PROTEINS; KINETICS AB We have studied the kinetics of low-pH-induced fusion between erythrocyte membranes and membranes containing influenza virus hemagglutinin by using assays based on the fluorescence dequenching of the lipophilic dye octadecylrhodamine. Stopped-flow mixing and fast data acquisition have been used to monitor the early stages of influenza virus fusion. We have compared this with the kinetics observed for fusion of an NIH 3T3 cell line, transformed with bovine papillomavirus, which constitutively expresses influenza virus hemagglutinin (GP4f cells). Virus and GP4f cells both display a pH-dependent time lag before the onset of fluorescence dequenching, but of an order of magnitude difference, ca. 2 s versus ca. 20 s. We have adopted two strategies to investigate whether the difference in lag time reflects the surface density of acid-activated hemagglutinin, able to undergo productive conformational change. (i) Hemagglutinin expressed on the cell surface requires proteolytic cleavage with trypsin from an inactive HA0 form; we have limited the extent of proteolysis. (ii) We have used infection of CV-1 cells with a recombinant simina virus 40 bearing the influenza virus hemagglutinin gene. The surface expression of hemagglutinin is a function of time postinfection. For low-pH-induced fusion of both types of cell with erythrocytes, the lag time decreases with increasing hemagglutinin densities. Our results do not indicate a cooperative phenomenon at the level of the principal rate-determining step. We also show in the instance of virus fusion, that the magnitude of the delay time is a function of the target membrane transbilayer lipid distribution. We conclude that for a given amount of pH-activated hemagglutinin per unit area of membrane, the kinetics of fusion is determined by nonspecific physical properties of the membranes involved. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BLDG 10,ROOM 4B56,BETHESDA,MD 20892. OI Clague, Michael/0000-0003-3355-9479 NR 19 TC 92 Z9 92 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1991 VL 65 IS 5 BP 2402 EP 2407 PG 6 WC Virology SC Virology GA FG777 UT WOS:A1991FG77700031 PM 1850019 ER PT J AU FALGOUT, B PETHEL, M ZHANG, YM LAI, CJ AF FALGOUT, B PETHEL, M ZHANG, YM LAI, CJ TI BOTH NONSTRUCTURAL PROTEINS NS2B AND NS3 ARE REQUIRED FOR THE PROTEOLYTIC PROCESSING OF DENGUE VIRUS NONSTRUCTURAL PROTEINS SO JOURNAL OF VIROLOGY LA English DT Article ID BORNE ENCEPHALITIS-VIRUS; AMINO-ACID SEQUENCE; YELLOW-FEVER VIRUS; WEST NILE VIRUS; PARTIAL NUCLEOTIDE-SEQUENCE; NON-STRUCTURAL PROTEINS; NEW-GUINEA-C; POSITIVE IDENTIFICATION; POLYMERASE-ACTIVITY; TERMINAL SEQUENCES AB The cleavages at the junctions of the flavivrus nonstructural (NS) proteins NS2A/NS2B, NS2B/NS3, NS3/NS4A, and NS4B/NS5 share an amino acid sequence motif and are presumably catalyzed by a virus-encoded protease. We constructed recombinant vaccinia viruses expressing various portions of the NS region of the dengue virus type 4 polyprotein. By analyzing immune precipitates of S-35-labeled lysates of recombinant virus-infected cells, we could monitor the NS2A/NS2B, NS2B/NS3, and NS3/NS4A cleavages. A polyprotein composed of NS2A, NS2B, and the N-terminal 184 amino acids of NS3 was cleaved at the NS2A/NS2B and NS2B/NS3 junctions, whereas a similar polyprotein containing only the first 77 amino acids of NS3 was not cleaved. This finding is consistent with the proposal that the N-terminal 180 amino acids of NS3 constitute a protease domain. Polyproteins containing NS2A and NS3 with large in-frame deletions of NS2B were not cleaved at the NS2A/NS2B or NS2B/NS3 junctions. Coinfection with a recombinant expressing NS2B complemented these NS2B deletions for NS2B/NS3 cleavage and probably also for NS2A/NS2B cleavage. Thus, NS2B is also required for the NS2A/NS2B and NS2B/NS3 cleavages and can act in trans. Other experiments showed that NS2B was needed, apparently in cis, for NS3/NS4A cleavage and for a series of internal cleavages in NS3. Indirect evidence that NS3 can also act in trans was obtained. Models are discussed for a two-component protease activity requiring both NS2B and NS3. C1 NIAID,INFECT DIS LAB,MOLEC VIROL BIOL SECT,BETHESDA,MD 20892. NR 59 TC 328 Z9 341 U1 1 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1991 VL 65 IS 5 BP 2467 EP 2475 PG 9 WC Virology SC Virology GA FG777 UT WOS:A1991FG77700040 PM 2016768 ER PT J AU CZUB, M CZUB, S MCATEE, FJ PORTIS, JL AF CZUB, M CZUB, S MCATEE, FJ PORTIS, JL TI AGE-DEPENDENT RESISTANCE TO MURINE RETROVIRUS-INDUCED SPONGIFORM NEURODEGENERATION RESULTS FROM CENTRAL NERVOUS SYSTEM-SPECIFIC RESTRICTION OF VIRUS-REPLICATION SO JOURNAL OF VIROLOGY LA English DT Article ID WILD MOUSE RETROVIRUS; SINDBIS VIRUS; INFECTION; PARALYSIS; MICE; PATHOGENESIS; DISEASE; DNA AB The murine retrovirus CasBrE causes a noninflammatory spongiform degeneration of the central nervous system (CNS). Mice inoculated as neonates develop viremia and are susceptible to disease. However, mice inoculated at 10 days of age do not develop viremia and are totally resistant to the neurologic disease. We recently described a highly neurovirulent chimeric virus, FrCas(E) (J. L. Portis, S. Czub, C. F. Garon, and F. J. McAtee, J. Virol. 64:1648-1656, 1990), which contains the env gene of CasBrE. Mice inoculated at 10 days of age with this virus developed a viremia comparable to that in neonatally inoculated mice but, surprisingly, were still completely resistant to the neurodegenerative disease. A comparison of the tissue distribution of virus replication for mice inoculated at 1 or 10 days of age was determined by Southern blot analysis for the quantification of viral DNA and by infectious-center assay for the quantification of virus-producing cells. The levels of virus replication in the spleens were comparable in the two groups. In contrast, virus replication in the CNS of the resistant 10-day-old mice was markedly restricted (100- to 1,000-fold). Intracerebral inoculation did not overcome this restriction. A similar pattern of CNS-specific restriction of virus replication and resistance to disease was observed in athymic NIH Swiss nude mice inoculated at 10 days of age, suggesting that T-cell immunity was not involved. From our results, we conclude that the age-dependent resistance to disease is a consequence of the restriction of virus replication within the CNS due to the developmental state of the organ. RP CZUB, M (reprint author), NIAID, ROCKY MT LABS, PERSISTENT VIRAL DIS LAB, HAMILTON, MT 59840 USA. NR 31 TC 52 Z9 52 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 MAY PY 1991 VL 65 IS 5 BP 2539 EP 2544 PG 6 WC Virology SC Virology GA FG777 UT WOS:A1991FG77700049 PM 1850027 ER PT J AU GITLIN, SD LINDHOLM, PF MARRIOTT, SJ BRADY, JN AF GITLIN, SD LINDHOLM, PF MARRIOTT, SJ BRADY, JN TI TRANSDOMINANT HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I TAX1 MUTANT THAT FAILS TO LOCALIZE TO THE NUCLEUS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; TROPICAL SPASTIC PARAPARESIS; COLONY-STIMULATING FACTOR; RECEPTOR GENE-EXPRESSION; LEUKEMIA-VIRUS; INTERLEUKIN-2 RECEPTOR; TRANSGENIC MICE; HTLV-I; SEQUENCE REQUIREMENTS; FUNCTIONAL DISSECTION AB Human T-cell lymphotropic virus type I (HTLV-I) encodes a 40-kDa nuclear transactivating phosphoprotein, TAX1. The results presented in this study demonstrate that deletion of amino acids 2 through 59 of TAX1 (DELTA-58 TAX1) decreased transactivation of the HTLV-I long terminal repeat 10- to 20-fold. S1 nuclease analysis revealed that the decrease in transactivation of the HTLV-I long terminal repeat was associated with a lack of RNA synthesis. In contrast to the nuclear localization of the wild-type TAX1 protein, indirect immunofluorescence analysis demonstrated that DELTA-58 TAX1 failed to localize to the nucleus, indicating that the TAX1 nuclear localization sequence is present in amino acids 2 through 59. Cotransfection of wild-type and mutant TAX1 DNAs resulted in the cytoplasmic accumulation of TAX1 and a 25-fold decrease in transactivation. Although several possibilities which may account for this transdominant effect exist, we favor a model in which DELTA-58 TAX1 interferes with the nuclear localization of wild-type TAX1 protein, perhaps by forming heterodimer complexes. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 72 TC 47 Z9 47 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1991 VL 65 IS 5 BP 2612 EP 2621 PG 10 WC Virology SC Virology GA FG777 UT WOS:A1991FG77700058 PM 2016773 ER PT J AU ROMANCZUK, H VILLA, LL SCHLEGEL, R HOWLEY, PM AF ROMANCZUK, H VILLA, LL SCHLEGEL, R HOWLEY, PM TI THE VIRAL TRANSCRIPTIONAL REGULATORY REGION UPSTREAM OF THE E6 AND E7 GENES IS A MAJOR DETERMINANT OF THE DIFFERENTIAL IMMORTALIZATION ACTIVITIES OF HUMAN PAPILLOMAVIRUS TYPE-16 AND TYPE-18 SO JOURNAL OF VIROLOGY LA English DT Note ID PRIMARY HUMAN KERATINOCYTES; CERVICAL-CARCINOMA; DNA; TRANSFORMATION; CANCER; SUFFICIENT; SEQUENCE; INVITRO AB The human papillomavirus types 16 (HPV-16) and 18 (HPV-18) can immortalize primary human keratinocytes. The region of the viral genome responsible for this function maps to the E6 and E7 genes and their respective upstream transcriptional regulatory sequences, the long control regions (LCRs). The HPV-18 LCR/E6/E7 is more efficient in this immortalization function than the analogous region of the HPV-16 genome, resembling the difference in the immortalization potentials of the two full-length viral genomes. This study was designed to examine the basis for the difference in HPV-16 and HPV-18 immortalization efficiencies. The E6 and E7 genes of either HPV-16 or HPV-18, when expressed from the same heterologous promoter, immortalized primary human keratinocytes with the same low efficiency, suggesting that the difference in immortalization activities was not due to the different E6 or E7 genes themselves but rather to a difference in the transcriptional regulatory regions upstream of these genes. The analysis of a series of chimeric HPV-16 and HPV-18 LCR/E6/E7 constructs confirmed this observation and further mapped the viral element responsible for the major difference in immortalization efficiency to the transcriptional regulatory region upstream of the E6 and E7 genes. C1 LUDWIG INST CANC RES,SAO PAULO,BRAZIL. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20007. RP ROMANCZUK, H (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. NR 25 TC 86 Z9 87 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1991 VL 65 IS 5 BP 2739 EP 2744 PG 6 WC Virology SC Virology GA FG777 UT WOS:A1991FG77700080 PM 1850048 ER PT J AU COHENMANSFIELD, J WERNER, P MARX, MS FREEDMAN, L AF COHENMANSFIELD, J WERNER, P MARX, MS FREEDMAN, L TI 2 STUDIES OF PACING IN THE NURSING-HOME SO JOURNALS OF GERONTOLOGY LA English DT Article ID WANDERING BEHAVIOR; AGITATION; RESIDENTS; DEMENTIA AB Two studies concerning pacing by nursing home residents are presented. The first was a cross-sectional survey of 402 residents, which found that 39% of the subjects were pacers. In comparison to residents who did not pace, the pacers had fewer medical diagnoses, better appetites, and had resided in the facility for fewer years. Additionally, pacing was positively related to cognitive impairment and to past life-threatening experiences. Results of the second study, an observational study of six cognitively impaired residents who paced frequently, showed that these residents paced more when the environmental conditions were conducive to pacing (e.g., adequate lighting, enough room within which to pace). We believe that pacing is a reflection of good health within the nursing home population and suggest that caregivers may want to encourage rather than inhibit this behavior in some nursing home residents. C1 GEORGETOWN UNIV,CTR AGING,WASHINGTON,DC 20057. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP COHENMANSFIELD, J (reprint author), HEBREW HOME GREATER WASHINGTON,RES INST,6121 MONTROSE RD,ROCKVILLE,MD 20852, USA. FU NIA NIH HHS [R01 AG-08675]; NIMH NIH HHS [R01 MH-40758] NR 28 TC 43 Z9 44 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 MAY PY 1991 VL 46 IS 3 BP M77 EP M83 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA FX416 UT WOS:A1991FX41600017 PM 2030270 ER PT J AU VERDERY, RB GOLDBERG, AP AF VERDERY, RB GOLDBERG, AP TI HYPOCHOLESTEROLEMIA AS A PREDICTOR OF DEATH - A PROSPECTIVE-STUDY OF 224 NURSING-HOME RESIDENTS SO JOURNALS OF GERONTOLOGY LA English DT Article ID SERUM-CHOLESTEROL; PROGNOSTIC-SIGNIFICANCE; RHEUMATOID-ARTHRITIS; NUTRITIONAL-STATUS; MORTALITY RISK; MEN; LIPOPROTEIN; LIPOPOLYSACCHARIDE; ACYLTRANSFERASE; LECITHIN AB The relationship of cholesterol, albumin, hemoglobin and glucose levels, and anthropometric variables to risk of death was examined in all residents of a nursing home. Risk of death was a "U-shaped" function of the cholesterol levels. A tenfold increase in relative risk was associated with cholesterol < 3.4 mmol/l, and the least risk was associated with the middle tertile of cholesterol levels (4.0-5.0 mmol/l). For any level of plasma cholesterol, risk was constant with time for at least 6 months. Low albumin, low hemoglobin, and high fasting glucose levels were also associated with increased mortality; cholesterol levels were nonlinearly related to levels of these risk factors. Proportional hazards models showed that immobility, presence of decubitus ulcers of at least stage II, and use of enteral feeding were also risk factors for death. Because hypocholesterolemia correlated significantly (p < .05) with the presence of decubiti, elevated white blood cell count, and use of enteral feeding, the association between hypocholesterolemia and risk of death was most likely due to its association with malnutrition and infection. C1 JOHNS HOPKINS UNIV,FRANCIS SCOTT KEY MED CTR,SCH MED,BALTIMORE,MD 21218. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. FU NIA NIH HHS [1K01AG00414-01A2, P01 AG04402-05] NR 35 TC 40 Z9 40 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 MAY PY 1991 VL 46 IS 3 BP M84 EP M90 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA FX416 UT WOS:A1991FX41600018 PM 2030271 ER PT J AU NOVAK, MA SUOMI, SJ BOWMAN, RE MOHR, D AF NOVAK, MA SUOMI, SJ BOWMAN, RE MOHR, D TI PROBLEM-SOLVING IN ELDERLY SOPHISTICATED AND NAIVE MONKEYS SO JOURNALS OF GERONTOLOGY LA English DT Article ID SHORT-TERM-MEMORY; RHESUS-MONKEY; RETENTION; ADULTS AB Elderly (> 23 years) rhesus monkeys, some of whom had previous learning test experience, were tested on a standardized battery of discrimination and concept-formation tasks, and their performance was compared with that of test-naive middle-aged (15 years) and juvenile (2 years) monkeys. Naive elderly monkeys performed more poorly on virtually all tasks compared to their younger counterparts. In contrast, test-experienced elderly monkeys outperformed both middle-aged and juvenile monkeys on those problem types with which they had limited previous experience, despite the fact that 8-10 years had passed since their prior training. However, test-experienced elderly monkeys did not display superior performance on new tests that approximated visual acuity or assessed delayed discrimination capabilities. C1 NICHHD,BETHESDA,MD 20892. UNIV WISCONSIN,HARLOW PRIMATE LAB,MADISON,WI 53706. RP NOVAK, MA (reprint author), UNIV MASSACHUSETTS,DEPT PSYCHOL,AMHERST,MA 01003, USA. FU NIMH NIH HHS [MH-11894] NR 23 TC 3 Z9 3 U1 3 U2 3 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 MAY PY 1991 VL 46 IS 3 BP P102 EP P108 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA FX416 UT WOS:A1991FX41600023 PM 2030274 ER PT J AU SCHILLER, JH BITTNER, G MEISNER, LF OBERLEY, TD NORBACK, D SCHWABE, M FALTYNEK, CR RAABTRAUB, N AF SCHILLER, JH BITTNER, G MEISNER, LF OBERLEY, TD NORBACK, D SCHWABE, M FALTYNEK, CR RAABTRAUB, N TI ESTABLISHMENT AND CHARACTERIZATION OF AN EPSTEIN-BARR-VIRUS SPONTANEOUSLY TRANSFORMED LYMPHOCYTIC CELL-LINE DERIVED FROM A HAIRY-CELL LEUKEMIA PATIENT SO LEUKEMIA LA English DT Article ID ALPHA-INTERFERON; TAC ANTIGEN; NUDE-MICE; B-CELLS; THERAPY; PROLIFERATION; RETICULOENDOTHELIOSIS; MODULATION; RECEPTORS; INDUCTION AB Hairy cell leukemia is a rare, B-cell malignancy uniquely sensitive to the antitumor effects of alpha and beta interferons (IFN). In order to further study the effects of IFN in this disease, we derived a cell line (HC1) from the peripheral blood mononuclear cells of a patient with hairy cell leukemia (HCL). Cells exhibited the typical morphological features of HCL, including the characteristic cytoplasmic projections by light, transmission, and scanning electron microscopy. HC1 cells were of B-cell lineage, as evidenced by immunophenotypic analysis. Although originally TRAP positive, HC1 cells lost this biochemical marker following 3 months in culture. Monoclonality of the cell line was confirmed by a clonal karyotypic abnormality characteristic of B-cell malignancies, and the presence of a single, distinctive fused terminal EBV fragment. The cells formed colonies in soft agar and were tumorigenic in irradiated nude mice. HC1 cells were sensitive to the antiproliferative effects of IFN-alpha and IFN-beta, but only moderately sensitive to the growth inhibitory effects of IFN-gamma. Incubating the cells in the presence of Type 1 IFN resulted in stabilization of cell numbers, without cellular proliferation or loss. Cell cycle analysis revealed that IFN-alpha resulted in a build-up of cells in the S phase of the cell cycle, suggesting a cytostatic effect of IFN on the growth of these cells. The HC1 cell line provides a model system which will be useful for in vitro studies of the biology and treatment of this disease. C1 NCI,FREDERICK CANC RES FACIL,BIOCHEM PHYSIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21701. UNIV N CAROLINA,CHAPEL HILL,NC 27514. RP SCHILLER, JH (reprint author), UNIV WISCONSIN,WM S MIDDLETON VET ADM HOSP,CTR CLIN,DEPT MED,ONCOL SECT,MADISON,WI 53705, USA. NR 47 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1991 VL 5 IS 5 BP 399 EP 407 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA FQ559 UT WOS:A1991FQ55900008 PM 1851909 ER PT J AU WADHWANI, KC KOISTINAHO, J BALBO, A RAPOPORT, SI AF WADHWANI, KC KOISTINAHO, J BALBO, A RAPOPORT, SI TI BLOOD-NERVE AND BLOOD-BRAIN-BARRIER PERMEABILITIES AND NERVE VASCULAR SPACE IN FISCHER-344 RATS OF DIFFERENT AGES SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE SCIATIC NERVE; TIBIAL NERVE; ENDONEURIAL BLOOD VESSELS; SUCROSE PERMEABILITY; BLOOD-BRAIN BARRIER; AUTORADIOGRAPHY; AGING; RAT ID PERIPHERAL-NERVE; SCIATIC-NERVE; FACILITATED TRANSPORT; CAPILLARIES; METABOLISM; GLUCOSE; INVITRO; FIBERS; RABBIT AB The permeability-surface area product (PA) of [H-3]- or [C-14]sucrose at the blood-nerve barrier (BNB) of the sciatic nerve; and at the blood-brain barrier (BBB), were determined in Fischer-344 rats at 3, 11 and 31 months of age. PA was determined by using an in vivo i.v. bolus injection of radiotracer with two-time point graphic and quantitative autoradiographic methods. Vascular space and water content of the tibial nerve of these rats also were determined using quantitative morphometry and dry and wet weight ratios, respectively. There was no significant difference between mean PA(BNB) in any age group [(PA(BNB) at 3 months = 1.2 +/- 0.1 (mean +/- S.E.), at 11 months = 1.8 +/- 0.3; and at 31 months = 1.4 +/- 0.2 x 10(-50 ml/s . g wet wt; n = 5- 8 rats], nor any difference in PA(BBB). The mean ratio (%) of surface area of endoneurial blood vessels/nerve cross-section of the tibial nerve also did not differ between any group [3 months: 16 +/- 2 vessels; mean surface area ratios = 2.20 +/- 0.10%, n = 5; 11 months: 22 +/- 3 vessels and 2.48 +/- 0.21%, n = 5; and at 31 months: 26 +/- 1 vessels and 2.40 +/- 0.23%, n = 4). The mean nerve water in rats at 31 months was 64.8 +/- 1.1% wet wt and did not differ from that at 11 months (66.0 +/- 0.6% wet wt) or at 3 months (65.1 +/- 1.0% wet wt) (n = 5-8 nerves). Our results indicate that BBB and BNB integrities are not altered in senescent Fischer-344 rats. RP WADHWANI, KC (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C1O3,BETHESDA,MD 20892, USA. NR 49 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD MAY PY 1991 VL 58 IS 2-3 BP 177 EP 190 DI 10.1016/0047-6374(91)90091-D PG 14 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA FP286 UT WOS:A1991FP28600006 PM 1875727 ER PT J AU BASSER, PJ ROTH, BJ AF BASSER, PJ ROTH, BJ TI STIMULATION OF A MYELINATED NERVE AXON BY ELECTROMAGNETIC INDUCTION SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE ELECTROMAGNETIC INDUCTION; MAGNETIC STIMULATION; MATHEMATICAL MODEL; PERIPHERAL NERVE; SCALING LAWS; THRESHOLD ID VARYING MAGNETIC-FIELDS; PERIPHERAL-NERVE; CONDUCTION; FIBERS; MODEL AB A model of electromagnetic stimulation predicts the transmembrane potential distribution along a myelinated nerve axon and the volume of stimulated tissue within a limb. Threshold stimulus strength is shown to be inversely proportional to the square of the axon diameter. It is inversely proportional to pulse duration for short pulses and independent of pulse duration for long ones. These results are also predicted by dimensional analysis. Two dimensionless numbers, S(em), the ratio of the induced transmembrane potential to the axon's threshold potential, and T(c)/T, the ratio of the pulse duration to the membrane time constant, summarise the dependence of threshold stimulus strength on pulse duration and axon diameter. RP BASSER, PJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,BETHESDA,MD 20892, USA. RI Roth, Bradley/A-4920-2008; Basser, Peter/H-5477-2011 NR 27 TC 85 Z9 88 U1 3 U2 9 PU PETER PEREGRINUS LTD PI HERTS PA SOUTHGATE HOUSE STEVENAGE PO BOX 8, HERTS, ENGLAND SG1 1HQ SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD MAY PY 1991 VL 29 IS 3 BP 261 EP 268 DI 10.1007/BF02446708 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA FR476 UT WOS:A1991FR47600005 PM 1943258 ER PT J AU CHEN, JW VANDEGEIJN, J GOFFMAN, T AF CHEN, JW VANDEGEIJN, J GOFFMAN, T TI EXTRA LETHAL DAMAGE DUE TO RESIDUAL INCOMPLETELY REPAIRED SUBLETHAL DAMAGE IN HYPERFRACTIONATED AND CONTINUOUS RADIATION TREATMENT SO MEDICAL PHYSICS LA English DT Article DE TIME-DOSE RESPONSE; LQ-MODEL; RADIOTHERAPY; RADIOBIOLOGY; INCOMPLETE REPAIR; SUBLETHAL DAMAGE; EXTRA LETHAL DAMAGE ID DOSE-RATE; MULTIPLE FRACTIONS; TISSUE-RESPONSE; CELL-SURVIVAL; IRRADIATION; MODEL; RADIOTHERAPY; RECOVERY; HEAD; NECK AB In the conventional linear-quadratic model of single-dose response, the alpha and beta-terms reflect lethal damage created during the delivery of a dose, from two different presumed molecular processes, one linear with dose, the other quadratic. With the conventional one-fraction-per-day (or less) regimens, the sublethal damage (SLD), presumably repairing exponentially over time, is essentially completely fixed by the time of the next dose of radiation. If this assumption is true, the effects of subsequent fractions of radiation should be independent, that is, there should be little, if any, reversible damage left from previous fractions, at the time of the next dose. For multiple daily fractions, or for the limiting case, continuous radiation, this simplification may overlook damaged cells that have had insufficient time for repair. A generalized method is presented for accounting for extra lethal damage (ELD) arising from such residual SLD for hyperfractionation and continuous irradiation schemes. It may help to predict differences in toxicity and tumor control, if any, obtained with "unconventional" treatment regimens. A key element in the present model is the finite size and the dynamic character of the pool of sublethal damage. Besides creating the usual linear and quadratic components of lethal damage, each new fraction converts a certain fraction of the existing SLD into ELD, and creates some new SLD. The expressions developed by Thames [Int. J. Radiat. Biol. 47, 319-339 (1987)] for fractionated treatment (the IR model) and by Dale [Br. J. Radiol. 58, 515-528 (1985); 59, 919-927 (1986)] for protracted and fractionated treatment are found to be similar to our results in the limiting case where the pool of SLD is very large (infinite). Calculations with the present model suggest that enhancement of radiation effect with hyperfractionation due to conversion of sublethal damage to lethal damage should be modest within current clinical schedules, because of the judicious use of 4-h or preferably longer interfraction times, which permit sufficient repair of SLD. Shorter interfraction times would increase conversion of SLD to ELD and might lead to an unacceptable increase in toxicity. In continuous radiation, use of the ELD concept enables fitting computed survival curves to published experimental survival curves demonstrating decrease of effectiveness of a given total dose for dose rates below a certain level: low dose rate effect. Inclusion of proliferation will help in gaining insight into the limiting dose rate at which irradiation becomes ineffective. RP CHEN, JW (reprint author), NCI,DCT,ROB,BETHESDA,MD 20892, USA. NR 23 TC 4 Z9 4 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY-JUN PY 1991 VL 18 IS 3 BP 488 EP 496 DI 10.1118/1.596729 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FR130 UT WOS:A1991FR13000022 PM 1870493 ER PT J AU DESCHRYVERKECSKEMETI, K GRAMLICH, TL CROFFORD, LJ RADER, JI PAGE, SW NEEDHAM, LL HILL, RH STERNBERG, EM AF DESCHRYVERKECSKEMETI, K GRAMLICH, TL CROFFORD, LJ RADER, JI PAGE, SW NEEDHAM, LL HILL, RH STERNBERG, EM TI MAST-CELL AND EOSINOPHIL INFILTRATION IN INTESTINAL-MUCOSA OF LEWIS RATS TREATED WITH L-TRYPTOPHAN IMPLICATED IN HUMAN EOSINOPHILIA-MYALGIA-SYNDROME SO MODERN PATHOLOGY LA English DT Article DE GASTROINTESTINAL LESIONS; L-TRYPTOPHAN ASSOCIATED EOSINOPHILIA MYALGIA SYNDROME ID CONNECTIVE-TISSUE DISEASE; SCLERODERMA; ASSOCIATION; FIBROBLASTS; ACTIVATION; INGESTION; FASCIITIS; ARTHRITIS; BIOLOGY AB A recently developed animal model for the L-tryptophan-associated eosinophilia myalgia syndrome was used to examine the small intestine and colon, because there is clinical involvement at these sites in patients. Increased perivascular inflammatory infiltrates rich in degranulating mast cells, eosinophils, and monocytes were seen in the lamina propria of experimental animals when compared with controls. L-Tryptophan-associated disease also shares many clinical features with idiopathic scleroderma/eosinophilic fasciitis, in which there is gastrointestinal involvement as well. These features are similar to those found in the recently described animal model. The apparent morphologic and clinical similarities between these entities suggest that the animal model is suitable for further studying the pathogenesis of the gastrointestinal involvement in all these diseases. C1 CASE WESTERN RESERVE UNIV,DEPT PATHOL,CLEVELAND,OH 44106. NIAMSD,BETHESDA,MD. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. CTR DIS CONTROL,ATLANTA,GA 30333. NIMH,ADAMHA,BETHESDA,MD 20892. RI Needham, Larry/E-4930-2011; Crofford, Leslie/J-8010-2013 NR 26 TC 17 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 1991 VL 4 IS 3 BP 354 EP 357 PG 4 WC Pathology SC Pathology GA FM217 UT WOS:A1991FM21700012 PM 2068062 ER PT J AU CLARK, CG DIAMOND, LS AF CLARK, CG DIAMOND, LS TI THE LAREDO STRAIN AND OTHER ENTAMOEBA-HISTOLYTICA-LIKE AMEBAS ARE ENTAMOEBA-MOSHKOVSKII SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE ENTAMOEBA-HISTOLYTICA; ENTAMOEBA-MOSHKOVSKII; TAXONOMY; RIBOSOMAL RNA GENE; POLYMERASE CHAIN REACTION; RIBOPRINTING AB A small number of Entamoeba isolates from humans, the best known of which is the 'Laredo' strain, have the ability to grow at room temperature. This peculiarity, along with other characteristics, distinguishes the strains from the human pathogen E. histolytica despite their being morphologically inseparable. In contrast, these 'E. histolytica-like' strains share several features with E. moshkovskii, which is most frequently isolated from polluted water. To examine the taxonomic relationships among these morphologically similar organisms, we have used polymerase chain reaction amplification of the small subunit ribosomal RNA gene combined with restriction fragment length polymorphism analysis, 'riboprinting'. The results clearly show that the 'E. histolytica-like' amoebae are indeed strains of E. moshkovskii, and not closely related to E. histolytica. RP CLARK, CG (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 31 TC 119 Z9 121 U1 0 U2 5 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 MAY PY 1991 VL 46 IS 1 BP 11 EP 18 PG 8 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA FJ361 UT WOS:A1991FJ36100002 PM 1677159 ER PT J AU YI, TL BOLEN, JB IHLE, JN AF YI, TL BOLEN, JB IHLE, JN TI HEMATOPOIETIC-CELLS EXPRESS 2 FORMS OF LYN KINASE DIFFERING BY 21 AMINO-ACIDS IN THE AMINO TERMINUS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; SIGNAL TRANSDUCTION; CATALYTIC DOMAINS; CD4 RECEPTOR; C-SRC; ACTIVATION; GENE; LYMPHOCYTES; PP60C-SRC; P56LCK AB cDNAs for the murine lyn protein tyrosine kinase gene were cloned from mouse bone marrow-derived monocytic cells. Comparison of the human and murine genes demonstrated a 94% homology in peptide sequence. Comparable to the human gene, murine lyn was found to be expressed in myeloid and B-lymphoid lineage cells. During the cloning, two types of cDNAs were obtained that differed by the presence (lynA) or absence (lynB) of 63 bp within the amino-terminal coding region of the gene. The genomic structure of the murine lyn gene demonstrates that the two types of lyn transcripts are derived from alternative splicing utilizing an internal splice donor site. Transcripts for both forms were found to be expressed in myeloid cells. lyn-specific antisera detected comparable levels of proteins of 56 and 53 kDa in hematopoietic cells. These 56- and 53-kDa proteins comigrated with proteins produced by in vitro translation or in vivo expression of the lynA and lynB cDNAs, respectively. The two forms had comparable in vitro kinase activities in immunoprecipitates and showed similar peptide patterns, with partial V8 digestion of the in vitro-phosphorylated proteins. The potential significance of the two lyn proteins is discussed. C1 ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. NCI, TUMOR VIRUS BIOL LAB, BETHESDA, MD 20892 USA. UNIV TENNESSEE, CTR HLTH SCI, DEPT BIOCHEM, MEMPHIS, TN 38163 USA. FU NCI NIH HHS [P30 CA21765]; NIDDK NIH HHS [R01 DK42932] NR 42 TC 128 Z9 132 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1991 VL 11 IS 5 BP 2391 EP 2398 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500006 PM 2017160 ER PT J AU FRIESEL, R DAWID, IB AF FRIESEL, R DAWID, IB TI CDNA CLONING AND DEVELOPMENTAL EXPRESSION OF FIBROBLAST GROWTH-FACTOR RECEPTORS FROM XENOPUS-LAEVIS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; CELL-GROWTH; MESODERM INDUCTION; FACTOR-I; NUCLEOTIDE-SEQUENCE; BOVINE BRAIN; GENE; DNA; IDENTIFICATION; BINDING AB The heparin-binding growth factors constitute a family of homologous polypeptides including basic and acidic fibroblast growth factors (FGFs). These factors participate in a variety of processes, including wound healing, angiogenesis, neuronal survival, and inductive events in the early amphibian embryo. We have isolated three closely related species of cDNA clones for Xenopus FGF receptors. One of these, designated XFGFR-A1, encodes an open reading frame of 814 amino acids. A second class encodes an identical amino acid sequence with the exception of an 88-amino-acid deletion near the 5' end. This species probably arises through alternative splicing. A third class of cDNA corresponding to the shorter form of XFGFR-A1 was isolated and shown to be 95% homologous and is designated XFGFR-A2. Xenopus FGF receptors are similar to FGF receptors from other species in that they contain a transmembrane domain, a tyrosine kinase domain split by a 14-amino-acid insertion, and a unique conserved stretch of eight acidic residues in the extracellular domain. Overexpression of Xenopus FGF receptor protein by transfection of COS1 cells with the corresponding cDNA in a transient expression vector leads to the appearance of new FGF binding sites on transfected cells, consistent with these cDNAs encoding for FGF receptors. RNA gel blot analysis demonstrates that Xenopus FGF receptor mRNA is a maternal message and is expressed throughout early development. When blastula-stage ectoderm is cultured in control amphibian salt solutions, Xenopus FGF receptor mRNA declines to undetectable levels by late neurula stages. However, when cultured in the presence of FGF of XTC mesoderm-inducing factor, Xenopus FGF receptor RNA expression is maintained. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 66 TC 88 Z9 89 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 MAY PY 1991 VL 11 IS 5 BP 2481 EP 2488 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500016 PM 1850097 ER PT J AU LEFEBVRE, P BERARD, DS CORDINGLEY, MG HAGER, GL AF LEFEBVRE, P BERARD, DS CORDINGLEY, MG HAGER, GL TI 2 REGIONS OF THE MOUSE MAMMARY-TUMOR VIRUS LONG TERMINAL REPEAT REGULATE THE ACTIVITY OF ITS PROMOTER IN MAMMARY CELL-LINES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GLUCOCORTICOID RECEPTOR; TRANSGENIC MICE; PROVIRAL DNA; MAMMALIAN-CELLS; ONCOGENE INT-1; TRANSCRIPTION; PROTEIN; BINDING; METHYLATION; GENES AB In vivo expression of the mouse mammary tumor virus (MMTV) is restricted to a few organs, with the highest rate of transcription found in the mammary gland. Using a series of mammary and nonmammary murine cell lines, we have identified two regulatory elements, located upstream of the hormone responsive element, that specifically regulate the MMTV promoter. The first element displays an enhancerlike activity and is coincident with the binding of a nuclear factor (designated MP4; position -1078 to -1052 in the long terminal repeat) whose presence is apparently restricted to mammary cell lines. The second regulatory region mediates a repressive activity and is mapped to the long terminal repeat segment from -415 to -483. This repression is specific for a particular subtype of mammary cells (RAC cells) able to grow under two differentiation states (A. Sonnenber, H. Daams, J. Calafat, and J. Hilgers, Cancer Res. 46:5913-5922, 1986). The MMTV promoter in mammary cell lines thus appears to be modulated by two cis-acting elements that are likely to be involved in tissue-specific expression in vivo. C1 NCI,EXPTL CARCINOGENESIS LAB,HORMONE ACT & ONCOGENESIS SECT,BETHESDA,MD 20892. NR 51 TC 83 Z9 83 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 MAY PY 1991 VL 11 IS 5 BP 2529 EP 2537 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500022 PM 1708094 ER PT J AU GONG, QH STERN, J DEAN, A AF GONG, QH STERN, J DEAN, A TI TRANSCRIPTIONAL ROLE OF A CONSERVED GATA-1 SITE IN THE HUMAN EPSILON-GLOBIN GENE PROMOTER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHICKEN BETA-GLOBIN; PORPHOBILINOGEN DEAMINASE GENE; NUCLEAR-PROTEIN FACTORS; ACCURATE TRANSCRIPTION; HYPERSENSITIVE SITES; NUCLEOTIDE-SEQUENCE; CHROMATIN STRUCTURE; ERYTHROID PROMOTER; BINDING-FACTOR; CACCC-BOX AB The epsilon-globin gene is the first of the human beta-like globin genes to be expressed during development. We have analyzed protein-DNA interactions in the epsilon-globin promoter region by DNase I footprinting and electrophoretic mobility shift experiments using nuclear extracts from K562 human erythroid cells and from nonerythroid HeLa cells. A restricted set of ubiquitous proteins, including Sp1, bound to regions of the promoter including the CACCC and CCAAT sites. Three interactions, at positions -213, -165, and +3 relative to the transcription start site, were erythroid specific and corresponded to binding of GATA-1, a transcription factor highly restricted to the erythroid lineage. Interestingly, the GATA-1 site at -165 has been conserved in the promoters of 10 mammalian embryonic globin genes. Point mutations demonstrate that GATA-1 binding to this site is necessary for interaction with an erythroid-specific enhancer but that in the absence of an enhancer, GATA-1 does not increase transcription. C1 NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NR 52 TC 54 Z9 54 U1 0 U2 1 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 MAY PY 1991 VL 11 IS 5 BP 2558 EP 2566 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500025 PM 2017165 ER PT J AU FANKHAUSER, C IZAURRALDE, E ADACHI, Y WINGFIELD, P LAEMMLI, UK AF FANKHAUSER, C IZAURRALDE, E ADACHI, Y WINGFIELD, P LAEMMLI, UK TI SPECIFIC COMPLEX OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV AND NUCLEOLAR B23 PROTEINS - DISSOCIATION BY THE REV RESPONSE ELEMENT SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANS-ACTIVATOR GENE; VIRAL MESSENGER-RNA; HTLV-III; HIV-1; REPLICATION; EXPRESSION; SEQUENCE; PRODUCT; BINDING; BACTERIOPHAGE-T4 AB The human immunodeficiency virus type 1 (HIV) Rev protein is thought to be involved in the export of unspliced or singly spliced viral mRNAs from the nucleus to the cytoplasm. This function is mediated by a sequence-specific interaction with a cis-acting RNA element, the Rev response element (RRE), present in these intron-containing RNAs. To identify possible host proteins involved in Rev function, we fractionated nuclear cell extracts with a Rev affinity column. A single, tightly associated Rev-binding protein was identified; this protein is the mammalian nucleolar protein B23. The interaction between HIV Rev and B23 is very specific, as it was observed in complex cell extracts. The complex is also very stable toward dissociation by high salt concentrations. Despite the stability of the Rev-B23 protein complex, the addition of RRE, but not control RNA, led to the displacement of B23 and the formation of a specific Rev-RRE complex. The mammalian nucleolar protein B23 or its amphibian counterpart No38 is believed to function as a shuttle receptor for the nuclear import of ribosomal proteins. B23 may also serve as a shuttle for the import of HIV Rev from the cytoplasm into the nucleus or nucleolus to allow further rounds of export of RRE-containing viral RNAs. C1 UNIV GENEVA,DEPT BIOCHEM,30 QUAI ERNEST ANSERMET,CH-1211 GENEVA 4,SWITZERLAND. UNIV GENEVA,DEPT MOLEC BIOL,CH-1211 GENEVA 4,SWITZERLAND. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. RI Izaurralde, Elisa/G-3239-2012; OI Izaurralde, Elisa/0000-0001-7365-2649 NR 44 TC 184 Z9 187 U1 0 U2 3 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 MAY PY 1991 VL 11 IS 5 BP 2567 EP 2575 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500026 PM 2017166 ER PT J AU CLARK, AB DYKSTRA, CC SUGINO, A AF CLARK, AB DYKSTRA, CC SUGINO, A TI ISOLATION, DNA-SEQUENCE, AND REGULATION OF A SACCHAROMYCES-CEREVISIAE GENE THAT ENCODES DNA STRAND TRANSFER PROTEIN-ALPHA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MEIOTIC RECOMBINATION; HETERODUPLEX DNA; BINDING PROTEINS; ESCHERICHIA-COLI; HUMAN-CELLS; YEAST; ATP; PURIFICATION; EXCHANGE; KINASE AB DNA strand transfer protein-alpha (STP-alpha) from meiotic Saccharomyces cerevisiae cells promotes homologous pairing of DNA without any nucleotide cofactor in the presence of yeast single-stranded DNA binding protein. This gene (DNA strand transferase 1, DST1) encodes a 309-amino-acid protein with a predicted molecular mass of 34,800 Da. The STP-alpha protein level is constant in both mitotic and meiotic cells, but during meiosis the polypeptide is activated by an unknown mechanism, resulting in a large increase in its specific activity. A dst1::URA3/dst1::URA3 mutant grows normally in mitotic media; however, meiotic cells exhibit a greatly reduced induction of both DNA strand transfer activity and intragenic recombination between his1 heteroalleles. Spore viability is normal. These results suggest that DST1 is required for much of the observed induction of homologous recombination in S. cerevisiae during meiosis but not for normal sporulation. C1 NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 37 TC 51 Z9 52 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 MAY PY 1991 VL 11 IS 5 BP 2576 EP 2582 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500027 PM 1850099 ER PT J AU DYKSTRA, CC KITADA, K CLARK, AB HAMATAKE, RK SUGINO, A AF DYKSTRA, CC KITADA, K CLARK, AB HAMATAKE, RK SUGINO, A TI CLONING AND CHARACTERIZATION OF DST2, THE GENE FOR DNA STRAND TRANSFER PROTEIN-BETA FROM SACCHAROMYCES-CEREVISIAE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING PROTEINS; TACTAAC BOX; YEAST; RECOMBINATION; PURIFICATION; EXCHANGE; MEIOSIS; ATP; SEQUENCE; MUTANTS AB The gene encoding the 180-kDa DNA strand transfer protein-beta from the yeast Saccharomyces cerevisiae was identified and sequenced. This gene, DST2 (DNA strand transferase 2), was located on chromosome VII. dst2 gene disruption mutants exhibited temperature-sensitive sporulation and a 50% longer generation time during vegetative growth than did the wild type. Spontaneous mitotic recombination in the mutants was reduced severalfold for both intrachromosomal recombination and intragenic gene conversion. The mutants also had reduced levels of the intragenic recombination that is induced during meiosis. Meiotic recombinants were, however, somewhat unstable in the mutants, with a decrease in recombinants and survival upon prolonged incubation in sporulation media. spo13 or spo13 rad50 mutations did not relieve the sporulation defect of dst2 mutations. A dst1 dst2 double mutant has the same phenotype as a dst2 single mutant. All phenotypes associated with the dst2 mutations could be complemented by a plasmid containing DST2. C1 NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 40 TC 80 Z9 81 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 MAY PY 1991 VL 11 IS 5 BP 2583 EP 2592 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500028 PM 1850100 ER PT J AU PERKINS, AS FISHEL, R JENKINS, NA COPELAND, NG AF PERKINS, AS FISHEL, R JENKINS, NA COPELAND, NG TI EVI-1, A MURINE ZINC FINGER PROTOONCOGENE, ENCODES A SEQUENCE-SPECIFIC DNA-BINDING PROTEIN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR-IIIA; REGULATORY PROTEINS; ESCHERICHIA-COLI; DEVELOPING LIMBS; GENE; EXPRESSION; DOMAINS; MOUSE; IDENTIFICATION; DISTINCT AB Evi-1 was originally identified as a common site of viral integration in murine myeloid tumors. Evi-1 encodes a 120-kDa polypeptide containing 10 zinc finger motifs located in two domains 380 amino acids apart and an acidic domain located carboxy terminal to the second set of zinc fingers. These features suggest that Evi-1 is a site-specific DNA-binding protein involved in the regulation of RNA transcription. We have purified Evi-1 protein from E. coli and have employed a gel shift-polymerase chain reaction method using random oligonucleotides to identify a high-affinity binding site for Evi-1. The consensus sequence for this binding site is TGACAAGATAA. Evi-1 protein specifically protects this motif from DNase I digestion. By searching the nucleotide sequence data bases, we have found this binding site both in sequences 5' to genes in putative or known regulatory regions and within intron sequences. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC MECH CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 55 TC 107 Z9 107 U1 0 U2 1 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 MAY PY 1991 VL 11 IS 5 BP 2665 EP 2674 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500036 PM 2017172 ER PT J AU RADZIOCH, D VARESIO, L AF RADZIOCH, D VARESIO, L TI C-FOS MESSENGER-RNA EXPRESSION IN MACROPHAGES IS DOWN-REGULATED BY INTERFERON-GAMMA AT THE POSTTRANSCRIPTIONAL LEVEL SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN MONOCYTIC DIFFERENTIATION; MURINE PERITONEAL-MACROPHAGES; PROTEIN KINASE-C; GENE-EXPRESSION; IFN-GAMMA; HEMATOPOIETIC-CELLS; RIBOSOMAL-RNA; INDUCTION; BETA; TRANSCRIPTION AB Treatment of macrophages with interferon-gamma (IFN-gamma) strongly decreased the induction of c-fos mRNA by 12-O-tetradecanoylphorbol-13-acetate (TPA), lipopolysaccharide, or calcium ionophore A23187 in macrophages. Under the same experimental conditions, IFN-gamma induced oligo(A) synthetase mRNA and did not affect the constitutive expression of transforming growth factor-beta mRNA, indicating that IFN-gamma did not induce general degradation of mRNAs. Run-on experiments indicated that c-fos was constitutively transcribed at low levels and that TPA augmented c-fos transcription. IFN-gamma did not inhibit constitutive or TPA-induced c-fos transcription. However, IFN-gamma decreased c-fos mRNA stability, as assessed by measuring the half-life of c-fos mRNA in actinomycin D-treated cells. These results indicated that IFN-gamma inhibited c-fos mRNA induction by TPA at the posttranscriptional level. C1 NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. RP RADZIOCH, D (reprint author), MCGILL UNIV,MONTREAL GEN HOSP,MONTREAL H3G 1A4,QUEBEC,CANADA. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 FU NCI NIH HHS [N01-CO-74102] NR 37 TC 46 Z9 46 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 MAY PY 1991 VL 11 IS 5 BP 2718 EP 2722 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500041 PM 1901945 ER PT J AU MOEHLE, CM HINNEBUSCH, AG AF MOEHLE, CM HINNEBUSCH, AG TI ASSOCIATION OF RAP1 BINDING-SITES WITH STRINGENT CONTROL OF RIBOSOMAL-PROTEIN GENE-TRANSCRIPTION IN SACCHAROMYCES-CEREVISIAE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID UPSTREAM ACTIVATING SEQUENCES; AMINO-ACID BIOSYNTHESIS; CYTOCHROME-C GENE; ESCHERICHIA-COLI; GEL-ELECTROPHORESIS; MUTATIONAL ANALYSIS; RIBONUCLEIC-ACID; RELAXED MUTANT; RNA-SYNTHESIS; PEP4 GENE AB An amino acid limitation in bacteria elicits a global response, called stringent control, that leads to reduced synthesis of rRNA and ribosomal proteins and increased expression of amino acid biosynthetic operons. We have used the antimetabolite 3-amino-1,2,4-triazole to cause histidine limitation as a means to elicit the stringent response in the yeast Saccharomyces cerevisiae. Fusions of the yeast ribosomal protein genes RPL16A, CRY1, RPS16A, and RPL25 with the Escherichia coli lacZ gene were used to show that the expression of these genes is reduced by a factor of 2 to 5 during histidine-limited exponential growth and that this regulation occurs at the level of transcription. Stringent regulation of the four yeast ribosomal protein genes was shown to be associated with a nucleotide sequence, known as the UAS(rpg) (upstream activating sequence for ribosomal protein genes), that binds the transcriptional regulatory protein RAP1. The RAP1 binding sites also appeared to mediate the greater ribosomal protein gene expression observed in cells growing exponentially than in cells in stationary phase. Although expression of the ribosomal protein genes was reduced in response to histidine limitation, the level of RAP1 DNA-binding activity in cell extracts was unaffected. Yeast strains bearing a mutation in any one of the genes GCN1 to GCN4 are defective in derepression of amino acid biosynthetic genes in 10 different pathways under conditions of histidine limitation. These Gcn- mutants showed wild-type regulation of ribosomal protein gene expression, which suggests that separate regulatory pathways exist in S. cerevisiae for the derepression of amino acid biosynthetic genes and the repression of ribosomal protein genes in response to amino acid starvation. RP MOEHLE, CM (reprint author), NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892, USA. NR 73 TC 125 Z9 125 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1991 VL 11 IS 5 BP 2723 EP 2735 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500042 PM 2017175 ER PT J AU DECLUE, JE ZHANG, K REDFORD, P VASS, WC LOWY, DR AF DECLUE, JE ZHANG, K REDFORD, P VASS, WC LOWY, DR TI SUPPRESSION OF SRC TRANSFORMATION BY OVEREXPRESSION OF FULL-LENGTH GTPASE-ACTIVATING PROTEIN (GAP) OR OF THE GAP-C TERMINUS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RAS P21 GTPASE; TYROSINE KINASES; CELL-TRANSFORMATION; SARCOMA-VIRUS; ONCOGENE; GENE; PHOSPHORYLATION; IDENTIFICATION; INDUCTION; MUTANTS AB Overexpression of the full-length GTPase-activating protein (GAP) has recently been shown to suppress c-ras transformation of NIH 3T3 cells but not v-ras transformation (36). Here, we show that focus formation induced by c-src was inhibited by approximately 80% when cotransfected with a plasmid encoding full-length GAP. In a similar assay, focus formation by the activated c-src (Tyr-527 to Phe) gene was inhibited by 33%. Cotransfection of the GAP C terminus coding sequences (which encode the GTPase-accelerating domain) with c-src or c-src527F inhibited transformation more efficiently than did the full-length GAP, while the GAP N terminus coding sequences had no effect on src transformation. When cells transformed by c-ras, c-src, c-src527F, or v-src were transfected with GAP or the GAP C terminus sequence in the presence of a selectable marker, 40 to 85% of the resistant colonies were found to be morphologically revertant. The GAP C terminus induced reversion of each src-transformed cell line more efficiently than the full-length GAP, but this was not the case for reversion of c-ras transformation. Biochemical analysis of v-src revertant subclones showed that the reversion correlated with overexpression of full-length GAP or the GAP C terminus. There was no decrease in the level of pp60src expression or the level of protein-tyrosine phosphorylation in vivo. We conclude that GAP can suppress transformation by src via inhibition of endogenous ras activity, without inhibiting in vivo tyrosine phosphorylation of cellular proteins induced by pp60src, and that src may negatively regulate GAP's inhibitory action on endogenous ras. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 37 TC 117 Z9 117 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 MAY PY 1991 VL 11 IS 5 BP 2819 EP 2825 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500053 PM 2017179 ER PT J AU WIDNER, WR MATSUMOTO, Y WICKNER, RB AF WIDNER, WR MATSUMOTO, Y WICKNER, RB TI IS 20S RNA NAKED SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; YEAST; SPORULATION; HSP26 AB The 20S RNA of Saccharomyces cerevisiae is a single-stranded, circular RNA virus. A previous study suggested that this RNA is part of a 32S ribonucleoprotein particle, being associated with multiple copies of a 23-kilodalton protein. We show here that this protein is, in fact, the chromosome-encoded heat shock protein Hsp26. Furthermore, it is apparently not associated with 20S RNA and plays no obvious role in the life cycle of the virus. RP WIDNER, WR (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BLDG 8,ROOM 207,BETHESDA,MD 20892, USA. NR 18 TC 20 Z9 21 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 MAY PY 1991 VL 11 IS 5 BP 2905 EP 2908 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FJ155 UT WOS:A1991FJ15500064 PM 2017185 ER PT J AU LEROITH, D ROBERTS, CT AF LEROITH, D ROBERTS, CT TI INSULIN-LIKE GROWTH-FACTOR I (IGF-I) - A MOLECULAR-BASIS FOR ENDOCRINE VERSUS LOCAL-ACTION SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE INSULIN-LIKE GROWTH FACTOR-I; ENDOCRINE; PARACRINE ID MESSENGER RIBONUCLEIC-ACID; HORMONAL-REGULATION; BINDING-PROTEINS; FACTOR RECEPTORS; GENE-EXPRESSION; RAT; SEQUENCE; SOMATOMEDIN; CELLS; RNAS RP LEROITH, D (reprint author), NIDDK,MOLEC & CELLULAR PHYSIOL SECT,DIABETES BRANCH,BLDG 10,ROOM 8S243,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 68 Z9 68 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY PY 1991 VL 77 IS 1-3 BP C57 EP C61 DI 10.1016/0303-7207(91)90054-V PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA FL688 UT WOS:A1991FL68800002 PM 1815991 ER PT J AU WAYNE, RK VANVALKENBURGH, B OBRIEN, SJ AF WAYNE, RK VANVALKENBURGH, B OBRIEN, SJ TI MOLECULAR DISTANCE AND DIVERGENCE TIME IN CARNIVORES AND PRIMATES SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE MOLECULAR EVOLUTION; CARNIVORES; PRIMATES; DIVERGENCE TIME ID DIMENSIONAL PROTEIN ELECTROPHORESIS; MITOCHONDRIAL-DNA; GENETIC-DISTANCE; BIOCHEMICAL EVOLUTION; HUMAN ORIGINS; RATES; PHYLOGENY; DROSOPHILA; EXTINCTION; SPECIATION AB Numerous studies have used indices of genetic distance between species to reconstruct evolutionary relationships and to estimate divergence time. However, the empirical relationship between molecular-based indices of genetic divergence and divergence time based on the fossil record is poorly known. To date, the results of empirical studies conflict and are difficult to compare because they differ widely in their choice of taxa, genetic techniques, or methods for calibrating rates of molecular evolution. We use a single methodology to analyze the relationship of molecular distance and divergence time in 86 taxa (72 carnivores and 14 primates). These taxa have divergence times of 0.01-55 Myr and provide a graded series of phylogenetic divergences such that the shape of the curve relating genetic distance and divergence time is often well defined. The techniques used to obtain genetic distance estimates include one- and two-dimensional protein electrophoresis, DNA hybridization, and microcomplement fixation. Our results suggest that estimates of molecular distance and divergence time are highly correlated. However, rates of molecular evolution are not constant; rather, in general they decline with increasing divergence time in a linear fashion. The rate of decline may differ according to technique and taxa. Moreover, in some cases the variability in evolutionary rates changes with increasing divergence time such that the accuracy of nodes in a phylogenetic tree varies predictably with time. C1 NCI,VIRAL CARCINOGENESIS LAB,BETHESDA,MD 20892. RP WAYNE, RK (reprint author), UNIV CALIF LOS ANGELES,DEPT BIOL,LOS ANGELES,CA 90024, USA. NR 83 TC 98 Z9 104 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD MAY PY 1991 VL 8 IS 3 BP 297 EP 319 PG 23 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA FH396 UT WOS:A1991FH39600003 PM 2072860 ER PT J AU WALLACE, WC BRAGIN, V ROBAKIS, NK SAMBAMURTI, K VANDERPUTTEN, D MERRIL, CR DAVIS, KL SANTUCCI, AC HAROUTUNIAN, V AF WALLACE, WC BRAGIN, V ROBAKIS, NK SAMBAMURTI, K VANDERPUTTEN, D MERRIL, CR DAVIS, KL SANTUCCI, AC HAROUTUNIAN, V TI INCREASED BIOSYNTHESIS OF ALZHEIMER AMYLOID PRECURSOR PROTEIN IN THE CEREBRAL-CORTEX OF RATS WITH LESIONS OF THE NUCLEUS BASALIS OF MEYNERT SO MOLECULAR BRAIN RESEARCH LA English DT Article DE ALZHEIMER AMYLOID PRECURSOR PROTEIN; ALZHEIMERS DISEASE; PROTEIN SYNTHESIS; NUCLEUS BASALIS OF MEYNERT; GENE EXPRESSION; POLYSOME ID DISEASE; CDNA; GENE; EXPRESSION; ASTROCYTES; CULTURES; CLEAVAGE; NERVE AB The nucleus basalis of Meynert was lesioned by infusion of N-methyl-D-aspartate (NMDA) unilaterally in adult rat brain. Seven days post lesion we observed that polysomes isolated from the cerebral cortex affected by the lesion synthesized 2.6-fold greater amounts of the Alzheimer amyloid precursor protein (AAPP) compared to the nonlesioned side of the same rat brain. This increase exhibited specificity to AAPP in that overall protein synthesis was not altered by the lesion. The increase of AAPP did not alter the ratio of AAPP isotypes in rat brain (in which AAPP 695, which is lacking the protease inhibitor insert remains the predominant form). The increased synthesis did not result in the apparent accumulation of mature AAPP. These results indicate that a cholingeric lesion which models many of the neurochemical changes observed in Alzheimer's disease induces the expression of AAPP in a major projection region, the cerebral cortex. C1 CUNY MT SINAI SCH MED,ARTHUR M FISHBERG CTR NEUROBIOL,NEW YORK,NY 10029. ST ELIZABETH HOSP,NIMH,BIOCHEM GENET SECT,WASHINGTON,DC 20032. RP WALLACE, WC (reprint author), CUNY MT SINAI SCH MED,DEPT PSYCHIAT,1 GUSTAVE LEVY PL,NEW YORK,NY 10029, USA. NR 26 TC 89 Z9 89 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 MAY PY 1991 VL 10 IS 2 BP 173 EP 178 DI 10.1016/0169-328X(91)90108-A PG 6 WC Neurosciences SC Neurosciences & Neurology GA FK349 UT WOS:A1991FK34900010 ER PT J AU HATFIELD, DL LEE, BJ PRICE, NM STADTMAN, TC AF HATFIELD, DL LEE, BJ PRICE, NM STADTMAN, TC TI SELENOCYSTEYL-TRANSFER RNA OCCURS IN THE DIATOM THALASSIOSIRA AND IN THE CILIATE TETRAHYMENA SO MOLECULAR MICROBIOLOGY LA English DT Article ID GENETIC-CODE; IDENTIFICATION; UGA; GLUTATHIONE; THERMOPHILA; PROTEIN; YEAST; READ AB Selenocysteyl-tRNAs that decode UGA were identified previously in animal and bacterial cells and the genes for these tRNAs have been shown to be widespread in animals and eubacteria. In the present study, we identify a selenocysteyl-tRNA that codes for UGA in Thalassiosira pseudonana, which is a diatom, and in Tetrahymena borealis, which is a ciliate. The fact that these very diverse unicellular organisms also contain a selenocysteyl-tRNA suggests that selenocysteine-containing proteins and the use of UGA as a codon for selenocysteine are widespread, if not ubiquitous, in nature. C1 MIT,DEPT CIVIL ENGN,RALPH M PARSONS LAB,CAMBRIDGE,MA 02139. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RP HATFIELD, DL (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 26 TC 28 Z9 28 U1 1 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 1991 VL 5 IS 5 BP 1183 EP 1186 DI 10.1111/j.1365-2958.1991.tb01891.x PG 4 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA FN127 UT WOS:A1991FN12700020 PM 1835508 ER PT J AU HERSHKOWITZ, N ROGAWSKI, MA AF HERSHKOWITZ, N ROGAWSKI, MA TI TETRAHYDROAMINOACRIDINE BLOCK OF N-METHYL-D-ASPARTATE-ACTIVATED CATION CHANNELS IN CULTURED HIPPOCAMPAL-NEURONS SO MOLECULAR PHARMACOLOGY LA English DT Note ID VOLTAGE-DEPENDENT BLOCK; MOUSE CENTRAL NEURONS; LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; POTASSIUM CHANNELS; 9-AMINO-1,2,3,4-TETRAHYDROACRIDINE THA; TETRAHYDRO-9-AMINOACRIDINE THA; SENILE DEMENTIA; NMDA RESPONSES; RECEPTOR AB The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel recording techniques. THA produced a concentration-dependent block of NMDA-evoked inward current responses (IC50, 190-mu-M at -60 mV), without affecting responses to quisqualate or kainate. THA block of NMDA responses was voltage dependent and was nearly completely relieved at positive holding potentials. Analysis of the voltage dependency indicated that the THA binding site senses 56% of the transmembrane electrostatic field. In single-channel recordings from outside-out membrane patches. THA appeared to reduce the frequency and duration of NMDA-evoked single-channel currents, without affecting the single-channel amplitude. The effects of THA on NMDA responses occur at concentrations 1-2 orders of magnitude greater than the therapeutic serum concentrations and, therefore, blockade of NMDA receptor-mediated responses is unlikely to contribute to the putative therapeutic action of THA. However, because NMDA receptors may play a critical role in cognitive and memory function. THA has the potential to produce undesirable central nervous system side effects at high doses. C1 NINCDS,MED NEUROL BRANCH,NEURONAL EXCITABIL SECT,BLDG 10,ROOM SN-248,BETHESDA,MD 20892. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 46 TC 22 Z9 23 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 MAY PY 1991 VL 39 IS 5 BP 592 EP 598 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FM550 UT WOS:A1991FM55000002 PM 1709720 ER PT J AU WALL, SJ YASUDA, RP HORY, F FLAGG, S MARTIN, BM GINNS, EI WOLFE, BB AF WALL, SJ YASUDA, RP HORY, F FLAGG, S MARTIN, BM GINNS, EI WOLFE, BB TI PRODUCTION OF ANTISERA SELECTIVE FOR M1-MUSCARINIC RECEPTORS USING FUSION PROTEINS - DISTRIBUTION OF M1-RECEPTORS IN RAT-BRAIN SO MOLECULAR PHARMACOLOGY LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; CHOLINERGIC RECEPTORS; ANTAGONIST BINDING; CEREBRAL-CORTEX; MESSENGER-RNAS; EXPRESSION; SUBTYPES; PIRENZEPINE; HYBRIDIZATION; ANTIBODIES AB A fragment of the cDNA encoding the third intracellular loop of the rat m1 muscarinic receptor was cloned, and the DNA was expressed in Escherichia coli as a fusion protein. The fusion protein was purified and utilized as an antigen to raise a polyclonal antiserum in rabbits. Chinese hamster ovary cells stably transfected with the cDNA encoding each of the five known subtypes of muscarinic receptor were used as tissue sources to test the antiserum. The antiserum was found to quantitatively immunoprecipitate m1 muscarinic receptors, while not precipitating m2, m3, m4, or m5 receptors. This selective antiserum was utilized to quantify the density of m1 muscarinic receptors in seven selected areas of the rat brain. Thus, cortex was found to contain approximately 0.8 pmol/mg of membrane protein, which represents 34% of the total density of muscarinic receptors. Similarly, hippocampus (1 pmol/mg; 47%), striatum (0.8 pmol/mg; 29%), and olfactory tubercule (0.9 pmol/mg; 35%) are rich in m1 receptors. In contrast, thalamus/hypothalamus contained only 0.15 pmol/mg, representing approximately 16% of the total density of muscarinic receptors, whereas pons/medulla (0.03 pmol/mg; 5%) and cerebellum (< 0.01 pmol/mg; 2%) had very low levels of expression of m1 receptors. The development of a selective antiserum has provided a means for the quantification of a specific subtype of muscarinic receptor in tissues, such as the brain, that express multiple subtypes. This methodology will be applicable not only to the other subtypes of muscarinic receptor but also to the subtypes of several other neurotransmitter receptors that lack selective drugs with which to study them. C1 UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,INST NEUROSCI,PHILADELPHIA,PA 19104. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP WOLFE, BB (reprint author), GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC 20007, USA. FU NIGMS NIH HHS [GM31155]; NINDS NIH HHS [NS26934] NR 26 TC 117 Z9 117 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1991 VL 39 IS 5 BP 643 EP 649 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FM550 UT WOS:A1991FM55000010 PM 2034236 ER PT J AU GRIESEMER, RA AF GRIESEMER, RA TI THE UNITED-STATES-NATIONAL-TOXICOLOGY-PROGRAM CARCINOGEN DATABASE - PREFACE SO MUTATION RESEARCH LA English DT Editorial Material RP GRIESEMER, RA (reprint author), NIEHS,DIV TOXICOL RES & TESTING,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 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 MAY PY 1991 VL 257 IS 3 BP 207 EP 207 DI 10.1016/0165-1110(91)90001-C PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA FG748 UT WOS:A1991FG74800001 ER PT J AU TENNANT, RW ASHBY, J AF TENNANT, RW ASHBY, J TI CLASSIFICATION ACCORDING TO CHEMICAL-STRUCTURE, MUTAGENICITY TO SALMONELLA AND LEVEL OF CARCINOGENICITY OF A FURTHER 39 CHEMICALS TESTED FOR CARCINOGENICITY BY THE UNITED-STATES-NATIONAL-TOXICOLOGY-PROGRAM SO MUTATION RESEARCH LA English DT Article DE RODENT CARCINOGENICITY BIOASSAY; DNA REACTIVITY; CLASSIFICATION ACCORDING TO CHEMICAL STRUCTURE MUTAGENICITY ID RATS AB This paper is an extension of compilations published previously in this journal. (Ashby and Tennant, 1988; Ashby et al., 1989). A summary of the rodent carcinogenicity bioassay data on a further 39 chemicals tested by the U.S. National Toxicology Program (NTP) is presented. An evaluation of each chemical for structural alerts to DNA-reactivity is also provided, together with a summary of its mutagenicity to Salmonella. Chemicals with an aliphatic nitro group (-C-NO2) have been added to the composite structure of DNA-reactive sub-groups. The 39 chemicals were numbered and evaluated as an extension of the earlier analysis of 264 NTP chemicals. The activity patterns and conclusions derived from the earlier studies are followed by these 39 chemicals, albeit a detailed analysis of the total database of 301 chemicals is reserved for the succeeding paper. C1 ICI PLC,CENT TOXICOL LAB,MACCLESFIELD SK10 4TJ,CHESHIRE,ENGLAND. NIEHS,RES TRIANGLE PK,NC 27709. NR 5 TC 109 Z9 110 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD MAY PY 1991 VL 257 IS 3 BP 209 EP 227 DI 10.1016/0165-1110(91)90002-D PG 19 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA FG748 UT WOS:A1991FG74800002 PM 2014033 ER PT J AU ASHBY, J TENNANT, RW AF ASHBY, J TENNANT, RW TI DEFINITIVE RELATIONSHIPS AMONG CHEMICAL-STRUCTURE, CARCINOGENICITY AND MUTAGENICITY FOR 301 CHEMICALS TESTED BY THE UNITED-STATES NTP SO MUTATION RESEARCH LA English DT Article DE RODENT CARCINOGENICITY BIOASSAY; DNA REACTIVITY; CLASSIFICATION ACCORDING TO CHEMICAL STRUCTURE MUTAGENICITY ID GENETIC TOXICITY; SALMONELLA; RATS; RODENTS; PROGRAM; ASSAY AB An analysis is presented in which are evaluated correlations among chemical structure, mutagenicity to Salmonella, and carcinogenicity to rats and mice among 301 chemicals tested by the U.S. NTP. Overall, there was a high correlation between structural alerts to DNA reactivity and mutagenicity, but the correlation of either property with carcinogenicity was low. If rodent carcinogenicity is regarded as a singular property of chemicals, then neither structural alerts nor mutagenicity to Salmonella are effective in its prediction. Given this, the database was fragmented and new correlations sought between the derived sub-groups. First, the 301 chemicals were segregated into six broad chemical groupings. Second, the rodent cancer data were partially segregated by target tissue. Using the previously assigned structural alerts to DNA reactivity (electrophilicity), the chemicals were split into 154 alerting chemicals and 147 non-alerting chemicals. The alerting chemicals were split into three chemical groups; aromatic amino/nitro-types, alkylating agents and miscellaneous structurally-alerting groups. The non-alerting chemicals were subjectively split into three broad categories; non-alerting, non-alerting containing a non-reactive halogen group, and non-alerting chemicals with minor concerns about a possible structural alert. The tumor data for all 301 chemicals are re-presented according to these six chemical groupings. The most significant findings to emerge from comparisons among these six groups of chemicals were as follows: (a) Most of the rodent carcinogens, including most of the 2-species and/or multiple site carcinogens, were among the structurally alerting chemicals. (b) Most of the structurally alerting chemicals were mutagenic; 84% of the carcinogens and 66% of the non-carcinogens, 100% of the 33 aromatic amino/nitro-type 2-species carcinogens were mutagenic. Thus, for structurally alerting chemicals, the Salmonella assay showed high sensitivity and low specificity (0.84 and 0.33, respectively). (c) Among the 147 non-alerting chemicals < 5% were mutagenic, whether they were carcinogens or non-carcinogens (sensitivity 0.04). C1 NIEHS,RES TRIANGLE PK,NC 27709. RP ASHBY, J (reprint author), ICI PLC,CENT TOXICOL LAB,MACCLESFIELD SK10 4TJ,CHESHIRE,ENGLAND. NR 33 TC 567 Z9 570 U1 5 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD MAY PY 1991 VL 257 IS 3 BP 229 EP 306 DI 10.1016/0165-1110(91)90003-E PG 78 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA FG748 UT WOS:A1991FG74800003 PM 1707500 ER PT J AU RAPOPORT, JL AF RAPOPORT, JL TI PHARMACOTHERAPY OF OBSESSIONAL-COMPULSIVE DISORDERS SO NERVENARZT LA German DT Note ID CLOMIPRAMINE TREATMENT; DESIPRAMINE; ADOLESCENTS; SYMPTOMS; NEUROSIS; CHILDREN RP RAPOPORT, JL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD MAY PY 1991 VL 62 IS 5 BP 318 EP 320 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA FK995 UT WOS:A1991FK99500012 PM 1865964 ER PT J AU BLAKE, MJ APPEL, NM JOSEPH, JA STAGG, CA ANSON, M DESOUZA, EB ROTH, GS AF BLAKE, MJ APPEL, NM JOSEPH, JA STAGG, CA ANSON, M DESOUZA, EB ROTH, GS TI MUSCARINIC ACETYLCHOLINE-RECEPTOR SUBTYPE MESSENGER-RNA EXPRESSION AND LIGAND-BINDING IN THE AGED RAT FOREBRAIN SO NEUROBIOLOGY OF AGING LA English DT Article DE QUANTITATIVE RECEPTOR AUTORADIOGRAPHY; LIGAND BINDING; AGING; INSITU HYBRIDIZATION ID ANTAGONIST BINDING; AUTORADIOGRAPHIC LOCALIZATION; QUINUCLIDINYL BENZILATE; ALZHEIMERS-DISEASE; BRAIN; PIRENZEPINE; CLONING; MEMORY; FAMILY; GENES AB Previous studies indicate that a 20-30% decline in muscarinic acetylcholine receptor binding occurs in localized areas of rat brain during aging. In this study, reduced [H-3]-quinuclidinyl benzilate binding was observed in striata from 24-25-month-old rats relative to 5-6-month-old animals using homogenate binding assays. To determine if the decline in receptor concentration occurs as a result of decreased receptor synthesis, the expression of the m1, m3, and m4 muscarinic receptor mRNAs as well as [H-3]-QNB binding were determined in adjacent sections of young and old male rats using in situ hybridization and in vitro receptor autoradiography respectively. A significant decline in collective muscarinic receptor binding as assessed by [H-3]-QNB was observed in the caudate putamen, olfactory tubercle, nucleus accumbens, and several frontal and parietal cortical areas. The only difference observed in muscarinic mRNA expression for any of the three subtypes examined was a decline in m1 hybridization in the olfactory tubercle. The results of this study demonstrate that the regional brain areas displaying age-related decreases in receptor binding do not correlate with those areas showing a decrease in muscarinic receptor expression. Apparently, the decline in muscarinic acetylcholine receptor density with age does not result from a decline in receptor gene expression. C1 NIDA,ADDICT RES CTR,NEUROBIOL LAB,BALTIMORE,MD 21224. RP BLAKE, MJ (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 33 TC 24 Z9 24 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1991 VL 12 IS 3 BP 193 EP 199 DI 10.1016/0197-4580(91)90097-4 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA FL391 UT WOS:A1991FL39100001 PM 1876225 ER PT J AU HOROWITZ, ME POPLACK, DG AF HOROWITZ, ME POPLACK, DG TI DEVELOPMENT OF CHEMOTHERAPY TREATMENT FOR PEDIATRIC BRAIN-TUMORS SO NEUROLOGIC CLINICS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; HUMAN MEDULLOBLASTOMA; PHASE-II; PRERADIATION CHEMOTHERAPY; RISK MEDULLOBLASTOMA; RANDOMIZED TRIAL; ANTICANCER DRUGS; CHILDREN; CHILDHOOD; TOLERANCE C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,LEUKEMIA BIOL SECT,BETHESDA,MD 20892. NR 35 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 1991 VL 9 IS 2 BP 363 EP 373 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA FM843 UT WOS:A1991FM84300009 PM 1944105 ER PT J AU KOLLER, WC LANGSTON, JW HUBBLE, JP IRWIN, I ZACK, M GOLBE, L FORNO, L ELLENBERG, J KURLAND, L RUTTENBER, AJ SPENCER, P TANNER, C TETRUD, J WILCOX, T ROMAN, G MAYEUX, R SMITH, M GOETZ, C AF KOLLER, WC LANGSTON, JW HUBBLE, JP IRWIN, I ZACK, M GOLBE, L FORNO, L ELLENBERG, J KURLAND, L RUTTENBER, AJ SPENCER, P TANNER, C TETRUD, J WILCOX, T ROMAN, G MAYEUX, R SMITH, M GOETZ, C TI DOES A LONG PRECLINICAL PERIOD OCCUR IN PARKINSONS-DISEASE SO NEUROLOGY LA English DT Article; Proceedings Paper CT SYMP ON PRECLINICAL DETECTION OF PARKINSONS DISEASE CY DEC 07-08, 1990 CL MIAMI, FL SP SANDOZ PHARM, SOMERSET PHARM, PARKINSONS EPIDEMIOL RES COMM ID AMYOTROPHIC LATERAL SCLEROSIS; DRUG-INDUCED PARKINSONISM; ENVIRONMENTAL-FACTORS; SENSORY SYMPTOMS; RISK-FACTORS; LEWY BODIES; HUMAN-BRAIN; SMOKING; DEPRESSION; ETIOLOGY C1 CALIF PARKINSONS FDN,SAN JOSE,CA. CTR DIS CONTROL,ATLANTA,GA 30333. ROBERT WOOD JOHNSON MED CTR,DEPT NEUROL,NEW BRUNSWICK,NJ. VET ADM MED CTR,DEPT PATHOL,PALO ALTO,CA 94304. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. NIH,BETHESDA,MD 20892. UNIV CALIF BERKELEY,SCH MED,BERKELEY,CA 94720. NINCDS,PARKINSONS EPIDEMIOL RES COMM,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NIOSH,CINCINNATI,OH 45226. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. RP KOLLER, WC (reprint author), UNIV KANSAS,MED CTR,DEPT NEUROL,39TH & RAINBOW BLVD,KANSAS CITY,KS 66103, USA. NR 107 TC 57 Z9 58 U1 0 U2 7 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1991 VL 41 IS 5 SU 2 BP 8 EP 13 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA FQ264 UT WOS:A1991FQ26400002 PM 2041599 ER PT J AU TANAKA, H ISHIKAWA, A GINNS, EI MIYATAKE, T TSUJI, S AF TANAKA, H ISHIKAWA, A GINNS, EI MIYATAKE, T TSUJI, S TI LINKAGE ANALYSIS OF JUVENILE PARKINSONISM TO TYROSINE-HYDROXYLASE GENE LOCUS ON CHROMOSOME-11 SO NEUROLOGY LA English DT Article ID MARKED DIURNAL FLUCTUATION; PROPOSED LINKAGE; INSULIN GENE; RECOMBINATION; PEDIGREES; SYMPTOMS; DYSTONIA; DISEASE; POWER; DNA AB We performed linkage analyses of juvenile parkinsonism with autosomal recessive inheritance (AR-JP) to chromosome 11p15.5 locus including tyrosine hydroxylase (TH), Harvey-ras-1 (HRAS), and insulin (INS) genes by analyzing genomic DNA from 28 members of seven Japanese AR-JP families containing 10 affected individuals. We used the methods of pairwise linkage analysis (LIPED) and multipoint linkage analysis (LINKAGE) for genetic linkage to the chromosome 11p15.5 markers and detected recombination events between AR-JP locus and TH gene. Multipoint linkage analysis excluded the linkage in the interval between TH and HRAS, as well as 11 cMo distal to TH and 8.5 cMo distal to HRAS, a total of approximately 23 cMo on chromosome 11p. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892. RP TANAKA, H (reprint author), NIIGATA UNIV,BRAIN RES INST,DEPT NEUROL,ASAHIMACHI DORI 1-757,NIIGATA 951,JAPAN. NR 21 TC 13 Z9 13 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1991 VL 41 IS 5 BP 719 EP 722 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA FK928 UT WOS:A1991FK92800022 PM 1674118 ER PT J AU PATNEAU, DK MAYER, ML AF PATNEAU, DK MAYER, ML TI KINETIC-ANALYSIS OF INTERACTIONS BETWEEN KAINATE AND AMPA - EVIDENCE FOR ACTIVATION OF A SINGLE RECEPTOR IN MOUSE HIPPOCAMPAL-NEURONS SO NEURON LA English DT Article ID AMINO-ACID RECEPTORS; SELECTIVE GLUTAMATE RECEPTORS; EMBRYONIC CHICK MOTONEURONS; METHYL-D-ASPARTATE; QUISQUALATE RECEPTORS; XENOPUS OOCYTES; ACETYLCHOLINE-RECEPTORS; FUNCTIONAL EXPRESSION; VOLTAGE-CLAMP; BINDING-SITES AB AMPA but not kainate produces a rapidly desensitizing response in mouse hippocampal neurons. The characteristic action of these agonists appears to arise from activation of a single receptor with active and desensitized states, for which AMPA and kainate have different relative affinity. The equilibrium potency of a series of five agonists that produce rapidly desensitizing responses at non-NMDA receptors (EC50 1-mu-M to 4 mM) was similar to their equilibrium potency for block of kainate responses. Increasing the concentration of kainate overcame such block, but in the presence of AMPA the rate of activation of responses to kainate was slowed. Conversely, in the presence of kainate the amplitude of rapidly desensitizing responses evoked by AMPA was reduced, and the rate of onset of desensitization was slowed. RP PATNEAU, DK (reprint author), NIH,DEV NEUROBIOL LAB,NEUROPHYSIOL & BIOPHYS SECT,BLDG 36,ROOM 2A21,BETHESDA,MD 20892, USA. RI Mayer, Mark/H-5500-2013 NR 44 TC 222 Z9 223 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 1991 VL 6 IS 5 BP 785 EP 798 DI 10.1016/0896-6273(91)90175-Y PG 14 WC Neurosciences SC Neurosciences & Neurology GA FM522 UT WOS:A1991FM52200011 PM 1673850 ER PT J AU XU, H KIM, CH ZHU, YC WEBER, RJ JACOBSON, AE RICE, KC ROTHMAN, RB AF XU, H KIM, CH ZHU, YC WEBER, RJ JACOBSON, AE RICE, KC ROTHMAN, RB TI (+)-CIS-3-METHYLFENTANYL AND ITS ANALOGS BIND PSEUDOIRREVERSIBLY TO THE MU OPIOID BINDING-SITE - EVIDENCE FOR PSEUDOALLOSTERIC MODULATION SO NEUROPHARMACOLOGY LA English DT Article DE OPIOIDS; METHYLFENTANYL; OPIOID RECEPTORS; ANALGESIA ID OPIATE RECEPTOR; AFFINITY; LIGAND; BRAIN; INVITRO; AGONIST; POTENCY AB Previous studies demonstrated that preincubation of membranes from the brain of the rat with 1-mu-M (+)-cis-3-methylfentanyl produced a wash-resistant inhibition of mu-receptor binding. The present study was designed to: (1) determine the mechanism by which (+)-cis-3-methylfentanyl produced a wash-resistant inhibition of mu-receptor binding, and (2) to generate a structure-activity study, using wash-resistant inhibition as the end-point. Pretreatment of membranes with 500 nM (+)-cis-3-methylfentanyl increased the K(d) of binding sites for [H-3]ohmefentanyl, without altering the B(max). The increase in the K(d) was only partially due to the presence of residual drug and was accompanied by an increase in the dissociation rate of the binding of [H-3]ohmefentanyl. Therefore, pretreatment of membranes with (+)-cis-3-methylfentanyl resulted in a lower affinity interaction of [H-3]ohmefentanyl with the mu-binding site, consistent with a model postulating pseudoallosteric modulation of mu-binding sites by (+)-cis-3-methylfentanyl and its analogs. The rank order of potencies for wash-resistant inhibition of the binding of [H-3]6-beta-fluoro-6-desoxyoxymorphone or [H-3]ohmefentanyl, was lofentanil > (+)-cis-3-methylfentanyl > ohmefentanyl > sufentanil. All other opioids tested (1-mu-M morphine, 1-mu-M naloxone, 1-mu-M fentanyl, 1-mu-M (+)-cyclazocine, 1-mu-M (-)-cis-3-methylfentanyl) did not act as wash-resistant inhibitors of mu-binding sites. Although the pseudoirreversible IC50 of these agents did not correlate with their ED50 values for producing antinociception, after intravenous administration, the authors speculate that this property, termed "pseudoirreversible inhibition", might contribute to the extraordinary potency of (+)-cis-3-methylfentanyl and its analogs as antinociceptive agents. C1 NIMH,LCS,RECEPTOR STUDIES UNIT,BETHESDA,MD 20892. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. ACAD SINICA,SHANGHAI INST MAT,NEUROPHARMACOL LAB,SHANGHAI 200031,PEOPLES R CHINA. NR 19 TC 14 Z9 14 U1 2 U2 3 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 MAY PY 1991 VL 30 IS 5 BP 455 EP 462 DI 10.1016/0028-3908(91)90006-W PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA FN388 UT WOS:A1991FN38800006 PM 1650928 ER PT J AU GAO, B DUNCAN, WC WEHR, TA AF GAO, B DUNCAN, WC WEHR, TA TI CLORGYLINE-INDUCED REDUCTION IN BODY-TEMPERATURE AND ITS RELATIONSHIP TO VIGILANCE STATES IN SYRIAN-HAMSTERS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE CLORGYLINE; REM SLEEP; BODY TEMPERATURE; SYRIAN HAMSTER; HYPOTHERMIA; CIRCADIAN RHYTHM ID MONOAMINE-OXIDASE INHIBITORS; SLEEP-WAKEFULNESS CYCLE; ANTI-DEPRESSANT DRUGS; REM-SLEEP; ENVIRONMENTAL-TEMPERATURE; AMBIENT-TEMPERATURE; CIRCADIAN-RHYTHM; WAKE ACTIVITY; DEPRIVATION; RATS AB The antidepressant drug clorgyline, a monoamine oxidase inhibitor (MAOI) that selectively inhibits MAO type A was administered chronically to Syrian hamsters. Twenty-four-hour EEG sleep and/or telemetered peritoneal temperature were monitored during selected sampling periods over four weeks. Chronic clorgyline treatment decreased rapid-eye-movement (REM) sleep time and body temperature during the first week. Incomplete tolerance to these effects developed during the second and third weeks. REM sleep and body temperature were correlated during chronic clorgyline treatment. Non-REM (NREM) sleep was elevated throughout chronic treatment. These results suggest that clorgyline's effects on REM and NREM sleep might be related to clorgyline's effects on thermoregulation and to the development of tolerance. However, causal relationships between clorgyline's effects on thermoregulation and the levels of REM and NREM sleep remain to be determined. C1 NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,BETHESDA,MD 20892. NR 39 TC 16 Z9 16 U1 0 U2 2 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 MAY PY 1991 VL 4 IS 3 BP 187 EP 197 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA FP066 UT WOS:A1991FP06600004 PM 2064718 ER PT J AU MORGAN, PF LINNOILA, M AF MORGAN, PF LINNOILA, M TI REGIONAL INDUCTION OF C-FOS MESSENGER-RNA BY NMDA - A QUANTITATIVE INSITU HYBRIDIZATION STUDY SO NEUROREPORT LA English DT Article DE C-FOS; MESSENGER RNA; NMDA; MK-801; INSITU HYBRIDIZATION; GLUTAMATE; RAT; DENTATE GYRUS; PIRIFORM CORTEX ID RAT-BRAIN; BINDING-SITES; MOUSE-BRAIN; EXPRESSION; PROTEIN; RECEPTORS; ACTIVATION; ONCOGENE; NEURONS; MK-801 AB THE regional expression of c-fos mRNA following acute NMDA administration has been mapped by quantitative in-situ hybridization using S-35-c-fos DNA probe. NMDA-induced expression of c-fos mRNA is discrete, largely restricted to the dentate gyrus of the hippocampus and piriform cortex. This distribution is different from the much more widespread distribution of NMDA receptors detected by ligand autoradiography. Expression of c-fos mRNA induced by 225 mg kg-1 NMDA was stereospecifically blocked by pretreatment with the NMDA receptor/ionophore complex blocker, MK-801. Large doses of NMDA (> 175 mg kg-1) were needed for increased expression of c-fos mRNA. Animals which had seizures after acute NMDA administration always had high levels of c-fos mRNA, but equally high levels of c-fos mRNA expression were found in some seizure-free animals. Thus overt seizure activity may not be necessary for c-fos mRNA expression. RP MORGAN, PF (reprint author), NIAAA,DICBR,CLIN STUDIES LAB,BLDG 10,ROOM 3C-102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 33 Z9 33 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 MAY PY 1991 VL 2 IS 5 BP 251 EP 254 DI 10.1097/00001756-199105000-00009 PG 4 WC Neurosciences SC Neurosciences & Neurology GA FR351 UT WOS:A1991FR35100009 PM 1912456 ER PT J AU MARTIN, RG AF MARTIN, RG TI CAVEAT-EMPTOR SO NEW BIOLOGIST LA English DT Editorial Material ID T-CELLS; DNA; MICE C1 NIDDKD,BETHESDA,MD 20892. NR 9 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 1043-4674 J9 NEW BIOL PD MAY PY 1991 VL 3 IS 5 BP 409 EP 411 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA GK720 UT WOS:A1991GK72000001 PM 1883809 ER PT J AU BROWN, S AF BROWN, S TI 4.5S RNA - DOES FORM PREDICT FUNCTION SO NEW BIOLOGIST LA English DT Review DE 4.5S RNA; ESCHERICHIA-COLI; TRANSLATION; PROTEIN SECRETION; 7S RNA; SIGNAL RECOGNITION PARTICLE (SRP) ID SIGNAL-RECOGNITION PARTICLE; SMALL RIBONUCLEIC-ACIDS; ESCHERICHIA-COLI K-12; S-RNA; NUCLEOTIDE-SEQUENCE; TRANSFER RNA(M1G)METHYLTRANSFERASE; RIBONUCLEOPROTEIN PARTICLE; PROTEIN TRANSLOCATION; GENE TRMD; 23S RNA C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702. OI Brown, Stanley/0000-0002-8453-8144 NR 54 TC 26 Z9 26 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD MAY PY 1991 VL 3 IS 5 BP 430 EP 438 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA GK720 UT WOS:A1991GK72000003 PM 1715753 ER PT J AU ABASTADO, JP MILLER, PF HINNEBUSCH, AG AF ABASTADO, JP MILLER, PF HINNEBUSCH, AG TI A QUANTITATIVE MODEL FOR TRANSLATIONAL CONTROL OF THE GCN4 GENE OF SACCHAROMYCES-CEREVISIAE SO NEW BIOLOGIST LA English DT Article ID OPEN READING FRAMES; POLYPEPTIDE-CHAIN INITIATION; AMINO-ACID BIOSYNTHESIS; UPSTREAM AUG CODONS; SARCOMA VIRUS-RNA; MESSENGER-RNA; PROTEIN-SYNTHESIS; START-SITE; FACTOR-II; MUTATIONS C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. NR 40 TC 32 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD MAY PY 1991 VL 3 IS 5 BP 511 EP 524 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA GK720 UT WOS:A1991GK72000013 PM 1883814 ER PT J AU KURMAN, RJ MALKASIAN, GD SEDLIS, A SOLOMON, D AF KURMAN, RJ MALKASIAN, GD SEDLIS, A SOLOMON, D TI FROM PAPANICOLAOU TO BETHESDA - THE RATIONALE FOR A NEW CERVICAL CYTOLOGIC CLASSIFICATION SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID TERM FOLLOW-UP; HISTOPATHOLOGICAL DIAGNOSIS; INTRAEPITHELIAL NEOPLASIA; DYSPLASIA; BEHAVIOR AB The Bethesda System for reporting cervical/vaginal diagnoses was introduced to replace the numerical Papanicolaou class designations, thereby facilitating precise communication between cytopathologist and clinician. The terminology for squamous epithelial lesions includes the following categories: 1) atypical squamous cells of undetermined significance; 2) squamous intraepithelial lesion (SIL), which encompasses the spectrum of squamous cell carcinoma precursors, divided into low-grade SIL (human papillomavirus [HPV]-associated cellular changes, mild dysplasia, and cervical intraepithelial neoplasia [CIN] I) and high-grade SIL (moderate dysplasia, severe dysplasia, and carcinoma in situ and CIN II and III); and 3) squamous cell carcinoma. The rationale for including HPV-related changes (koilocytosis) with CIN I within low-grade SIL is based on the morphologic, behavioral, and virologic similarity of these two lesions, which precludes their separation in a consistent and reliable fashion. For the same reasons, CIN II and III lesions have been combined within the category of high-grade SIL. The term "atypical squamous cells of undetermined significance" is used for cytologic findings that do not fulfill the criteria for defined benign reactive changes or SIL. Therefore, this term is more restricted in usage as compared with the wide range of interpretations previously ascribed to "atypia" or "inflammatory atypia." C1 JOHNS HOPKINS UNIV,SCH MED,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21205. MAYO CLIN & MAYO FDN,DEPT OBSTET & GYNECOL,ROCHESTER,MN 55905. SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,BROOKLYN,NY. NCI,CYTOPATHOL SECT,BETHESDA,MD 20892. RP KURMAN, RJ (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,ROOM 711,PATHOL BLDG,BALTIMORE,MD 21205, USA. NR 18 TC 65 Z9 68 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 1991 VL 77 IS 5 BP 779 EP 782 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA FJ431 UT WOS:A1991FJ43100028 PM 1849626 ER PT J AU ROSEN, MG MERKATZ, IR HILL, JG AF ROSEN, MG MERKATZ, IR HILL, JG TI CARING FOR OUR FUTURE - A REPORT BY THE EXPERT PANEL ON THE CONTENT OF PRENATAL-CARE SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID DIABETIC MOTHERS; PREGNANCY AB The report of the Expert Panel on Prenatal Care entitled Caring for Our Future: The Content of Prenatal Care was presented to the Assistant Secretary for Health, James Mason, MD, on October 2, 1989. The Panel noted the need for attention not only to the mother and fetus, but also to the infant and family. Besides traditional medical care concerns, the importance of psychosocial and environmental patient and family needs was emphasized. The Panel felt that the addition of the pre-conception visit to routine prenatal care made care more effective. Suggestions as to visit timing and content were made. The Panel noted the need for further understanding of many of the activities performed routinely in prenatal care. C1 PRESBYTERIAN HOSP,SLOANE HOSP WOMEN,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT OBSTET & GYNECOL,NEW YORK,NY 10032. MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT OBSTET & GYNECOL,BRONX,NY 10467. NICHHD,OFF SCI POLICY & ANAL,BETHESDA,MD 20892. NR 15 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 1991 VL 77 IS 5 BP 782 EP 787 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA FJ431 UT WOS:A1991FJ43100029 PM 2014096 ER PT J AU SCHNEIDER, ML KRAEMER, GW SUOMI, SJ AF SCHNEIDER, ML KRAEMER, GW SUOMI, SJ TI THE EFFECTS OF VESTIBULAR-PROPRIOCEPTIVE STIMULATION ON MOTOR MATURATION AND RESPONSE TO CHALLENGE IN RHESUS-MONKEY INFANTS SO OCCUPATIONAL THERAPY JOURNAL OF RESEARCH LA English DT Article DE VESTIBULAR STIMULATION; RHESUS MONKEYS ID CEREBRAL-PALSIED CHILDREN; MATERNAL MOBILITY; RELATIVE EFFICACY; RESPONSIVENESS; BEHAVIORS; MOTHERS; FEAR C1 NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. RP SCHNEIDER, ML (reprint author), UNIV WISCONSIN,DEPT THERAPEUT SCI,2175 MED SCI CTR,1300 UNIV AVE,MADISON,WI 53706, USA. NR 39 TC 9 Z9 9 U1 1 U2 1 PU AMER OCCUP THER FOUND INC PI ROCKVILLE PA 1383 PICCARD DR, ROCKVILLE, MD 20849-1725 SN 0276-1599 J9 OCCUP THER J RES JI Occup. Ther. J. Res. PD MAY-JUN PY 1991 VL 11 IS 3 BP 135 EP 154 PG 20 WC Rehabilitation SC Rehabilitation GA GA899 UT WOS:A1991GA89900002 ER PT J AU CARBONE, A GUSELLA, GL RADZIOCH, D VARESIO, L AF CARBONE, A GUSELLA, GL RADZIOCH, D VARESIO, L TI HUMAN HARVEY-RAS IS BIOCHEMICALLY DIFFERENT FROM KIRSTEN-RAS OR N-RAS SO ONCOGENE LA English DT Article ID PROTEIN KINASE-C; SERUM-RESPONSE ELEMENT; GROWTH-FACTOR; PHORBOL ESTER; ADENYLATE-CYCLASE; FOS EXPRESSION; TRANSFORMED FIBROBLASTS; ONCOGENE PRODUCT; NIH/3T3 CELLS; P21 PROTEINS AB The biochemical effects of the human H-, N- and K-ras oncogenes were studied. We analysed the induction of c-fos mRNA and protein by the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in exponentially growing NIH3T3 fibroblasts transformed by transfection with ras oncogenes. We found that H-ras has the unique ability to inhibit c-fos induction by TPA. In contrast, normal c-fos expression was induced by TPA in fibroblasts transformed by N- or K-ras or by the ras-unrelated oncogenes dbl and trk. The inhibition of c-fos induction by H-ras was not due to alteration in the binding of TPA to the transformed cells or to the selection of idiosyncratic clones. These results provide clear evidence that H-ras is functionally different from K- or N-ras. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. UNIV CATTOLICA DEL SACRO CUORE,IST ANAT PATOL,I-00168 ROME,ITALY. NCI,FREDERICK CANC RES & DEV CTR,INC DYN CORP,PROGRAM RESOURCES,FREDERICK,MD 21702. MCGILL UNIV,MONTREAL GEN HOSP,DEPT MED,MONTREAL H3G 1A4,QUEBEC,CANADA. RP VARESIO, L (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. RI varesio, luigi/J-8261-2016; OI varesio, luigi/0000-0001-5659-2218; CARBONE, Arnaldo/0000-0001-9695-5837 FU NCI NIH HHS [N01-CO-74102] NR 42 TC 38 Z9 39 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 1991 VL 6 IS 5 BP 731 EP 737 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GT825 UT WOS:A1991GT82500007 PM 1905005 ER PT J AU HELIN, K VELU, T MARTIN, P VASS, WC ALLEVATO, G LOWY, DR BEGUINOT, L AF HELIN, K VELU, T MARTIN, P VASS, WC ALLEVATO, G LOWY, DR BEGUINOT, L TI THE BIOLOGICAL-ACTIVITY OF THE HUMAN EPIDERMAL GROWTH-FACTOR RECEPTOR IS POSITIVELY REGULATED BY ITS C-TERMINAL TYROSINES SO ONCOGENE LA English DT Article ID ALTERED AUTOPHOSPHORYLATION SITES; FACTOR EGF RECEPTOR; KINASE-ACTIVITY; SELF-PHOSPHORYLATION; PROTEIN-KINASE; GENE-PRODUCT; INTERNALIZATION; PP60C-SRC; MUTATION; BINDING AB The epidermal growth factor receptor (EGF-R) C-terminus contains three conserved tyrosines (Y-1068, Y-1148, Y-1173) which are phosphorylated upon EGF activation. To clarify the functional role of these tyrosines, each has been mutated to phenylalanine and studied as single, double and triple mutants in the full length receptor. EGF-dependent transforming ability of the single point mutants is similar to that of the wild type, while that of double mutants is decreased and an even lower activity is present in the triple mutant. In each bioassay, including EGF-dependent focal transformation, growth in agar and growth in low serum, mutant receptors display a similar hierarchy of activity. The lower activity is intrinsic in the mutants since they are expressed at similar level as the wild type and bind EGF with similar affinity. Deletion mutants lacking the last 19 or 63 amino acids (Velu et al., 1989a) show a similar decline in biological activity when compared to the corresponding point mutants, although the reduction is more pronounced than with the point mutants. Deletion of the last 123 aa, which removes all three tyrosines (Dc123), results in a receptor that is almost inactive biologically. The EGF-R kinase activity is affected by tyrosine substitution since in vitro phosphorylation of exogenous substrates is reduced in the double and triple mutants. Autophosphorylation, in vivo and in vitro, is also reduced, but not totally abolished in the triple point mutant and Dc123 indicating the existence of other autophosphorylation sites. A new site of autophosphorylation is found in the Dc123 mutant. We conclude, therefore, that the tyrosines at the extreme C-terminus positively regulate the biological and transforming activity of the EGF-R, probably via autophosphorylation. C1 UNIV COPENHAGEN,INST MICROBIOL,OSTER FARIMAGSGADE 2A,DK-1353 COPENHAGEN,DENMARK. NIH,CELLULAR ONCOL LAB,BETHESDA,MD 20892. RP BEGUINOT, L (reprint author), UNIV COPENHAGEN,INST MICROBIOL,OSTER FARIMAGSGADE 2A,DK-1353 COPENHAGEN,DENMARK. NR 42 TC 40 Z9 41 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 1991 VL 6 IS 5 BP 825 EP 832 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GT825 UT WOS:A1991GT82500019 PM 1646987 ER PT J AU WOLFF, A SHIP, JA TYLENDA, CA FOX, PC BAUM, BJ AF WOLFF, A SHIP, JA TYLENDA, CA FOX, PC BAUM, BJ TI ORAL MUCOSAL APPEARANCE IS UNCHANGED IN HEALTHY, DIFFERENT-AGED PERSONS SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID POPULATION; PREVALENCE; MENOPAUSE; DENTURES; LESIONS AB Oral mucosal status in 182 different-aged, healthy, community-dwelling persons was evaluated. Ninety-four men and 88 women, ranging in age between 20 and 95 years, participated in this study. Oral mucosal status was assessed according to both subjective complaints and a semiquantitative clinical rating scale. No changes in either criterion were detected with increasing age. Oral mucosal status of the older subjects of this study was comparable to that found in a previous study with a randomly enrolled, noninstitutionalized older population in Iowa. The results of this study suggest that aging per se does not lead to changes in the appearance of oral mucosa. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892. NR 28 TC 19 Z9 20 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAY PY 1991 VL 71 IS 5 BP 569 EP 572 DI 10.1016/0030-4220(91)90364-I PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA FM266 UT WOS:A1991FM26600010 PM 2047098 ER PT J AU TSUCHIMOCHI, M PATRONAS, NJ RUTTIMANN, UE FOX, PC BACHER, JD WEBBER, RL AF TSUCHIMOCHI, M PATRONAS, NJ RUTTIMANN, UE FOX, PC BACHER, JD WEBBER, RL TI MAGNETIC-RESONANCE-IMAGING OF CANINE SALIVARY-GLANDS AFTER DUCTAL LIGATION AND STIMULATION BY PILOCARPINE SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID PAROTID MASSES; TONGUE; CT AB We performed magnetic resonance imaging in six dogs after submandibular ductal ligation on one side, followed by secretory stimulation with intraperitoneal injection of pilocarpine (5 mg/kg). On the images obtained after ductal ligation but before stimulation, there was no significant change in signal intensity on either side. After injection of pilocarpine the signal intensity of the ligated gland increased significantly (p < 0.01) in T2-weighted images and nonsignificantly in inversion recovery images, and remained constant in T1-weighted images. Significant (p < 0.01) volume increases of the glands after ligation and stimulation were measured for the T1, T2, and inversion recovery protocols. These findings likely reflect the retention of saliva caused by pilocarpine stimulation and the absence of drainage through the obstructed duct. The results indicate that the T2-weighted images obtained after pilocarpine stimulation may be useful for studying patients with disturbance of major salivary gland function and may provide an objective basis for the noninvasive diagnosis of unilateral stenosis. C1 NIDR,DIAGNOST SYST BRANCH,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. RP TSUCHIMOCHI, M (reprint author), NIPPON DENT UNIV,SCH DENT NIIGATA,DEPT ORAL & MAXILLOFACIAL SURG 2,1-8 HAMAURA CHO,NIIGATA 95,JAPAN. NR 18 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 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAY PY 1991 VL 71 IS 5 BP 635 EP 641 DI 10.1016/0030-4220(91)90376-N PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA FM266 UT WOS:A1991FM26600022 PM 2047108 ER PT J AU WELLEMS, TE AF WELLEMS, TE TI MOLECULAR-GENETICS OF DRUG-RESISTANCE IN PLASMODIUM-FALCIPARUM MALARIA SO PARASITOLOGY TODAY LA English DT Article ID THYMIDYLATE SYNTHASE GENE; ALTERED DIHYDROFOLATE-REDUCTASE; CHLOROQUINE RESISTANCE; PYRIMETHAMINE RESISTANCE; ANTIMALARIAL-DRUGS; SYNTHETASE GENE; PARASITES; AMPLIFICATION; CYCLOGUANIL; MECHANISM AB Resistance to dihydrofolate reductase inhibitors and resistance to chloroquine have been mapped to single genetic loci in Plasmodium falciparum. Specific point mutations in the dihydrofolate reductase gene confer different degrees of resistance to two dihydrofolate inhibitors, cycloguanil and pyrimethamine, depending on the positions of the mutations and the residues involved. The chloroquine resistance locus has been mapped to a 400 kilobase (kb) segment of chromosome 7 in a P. falciparum cross. Identification and characterization of genes within this segment should lead to an understanding of the rapid drug efflux mechanism responsible for chloroquine resistance*. RP WELLEMS, TE (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 42 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD MAY PY 1991 VL 7 IS 5 BP 110 EP 112 DI 10.1016/0169-4758(91)90168-N PG 3 WC Parasitology SC Parasitology GA FL516 UT WOS:A1991FL51600006 PM 15463460 ER PT J AU HACK, M HORBAR, JD MALLOY, MH TYSON, JE WRIGHT, E WRIGHT, L AF HACK, M HORBAR, JD MALLOY, MH TYSON, JE WRIGHT, E WRIGHT, L TI VERY-LOW-BIRTH-WEIGHT OUTCOMES OF THE NATIONAL-INSTITUTE-OF-CHILD-HEALTH-AND-HUMAN-DEVELOPMENT NEONATAL NETWORK SO PEDIATRICS LA English DT Article DE VERY LOW BIRTH WEIGHT; NEONATES; MORBIDITY; MORTALITY ID GESTATIONAL-AGE; INTENSIVE-CARE; INFANTS AB This report describes the neonatal outcomes of 1765 very low birth weight (< 1500 g) infants delivered from November 1987 through October 1988 at the seven participating centers of the National Institute of Child Health and Human Development Neonatal Intensive Care Network. Survival was 34% at < 751 g birth weight (range between centers 20% to 55%), 66% at 751 through 1000 g (range 42% to 75%), 87% at 1001 through 1250 g (range 84% to 91%), and 93% at 1251 through 1500 g (range 89% to 98%). By obstetric measures of gestation, survival was 23% at 23 weeks (range 0% to 33%), 34% at 24 weeks (range 10% to 57%), and 54% at 25 weeks (range 30% to 72%). Neonatal morbidity included respiratory distress (67%), symptomatic patent ductus arteriosus (25%), necrotizing enterocolitis (6%), septicemia (17%), meningitis (2%), urinary tract infection (4%), and intraventricular hemorrhage (45%, 18% grade III and IV). Morbidity increased with decreasing birth weight. Oxygen was administered for greater-than-or-equal-to 28 days to 79% of < 751-g birth weight infants (range between centers 67% to 100%), 45% of 751- through 1000-g infants (range 20% to 68%), and 13% of 1001- through 1500-g infants (range 5% to 23%). Ventilator support for greater-than-or-equal-to 28 days was given to 68% of infants at < 751 g, 29% at 751 through 1000 g, and 4% at > 1000 g. Hospital stay was 59 days for survivors vs 15 days for infants who died. Sixty-nine percent of survivors had subnormal (< 10th percentile) weight at discharge. The data demonstrate important intercenter variation of current neonatal outcomes, as well as differences in philosophy of care and definition and prevalence of morbidity. C1 NICHHD,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC 20052. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV TEXAS,DALLAS,TX 75230. UNIV VERMONT,MED CTR,BURLINGTON,VT 05405. NR 21 TC 393 Z9 400 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 1991 VL 87 IS 5 BP 587 EP 597 PG 11 WC Pediatrics SC Pediatrics GA FL115 UT WOS:A1991FL11500001 PM 2020502 ER PT J AU AULAKH, CS ZOHAR, J WOZNIAK, KM HILL, JL HAASS, M MURPHY, DL AF AULAKH, CS ZOHAR, J WOZNIAK, KM HILL, JL HAASS, M MURPHY, DL TI DIFFERENTIAL-EFFECTS OF ANTIDEPRESSANT TREATMENTS ON FENFLURAMINE-INDUCED INCREASES IN PLASMA PROLACTIN AND CORTICOSTERONE IN RATS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE FENFLURAMINE; CLORGYLINE; IMIPRAMINE; LITHIUM; RATS; PROLACTIN; CORTICOSTERONE ID MAJOR AFFECTIVE-DISORDERS; META-CHLOROPHENYLPIPERAZINE; SERUM PROLACTIN; GROWTH-HORMONE; SEROTONERGIC STIMULATION; LITHIUM-CARBONATE; BRAIN-SEROTONIN; ANORECTIC DRUG; SECRETION; TERM AB Intravenous administration of 5-HT releasing agent, fenfluramine, to rats produced increases in plasma prolactin and corticosterone concentrations. Short-term or long-term treatment with either clorgyline or imipramine did not affect baseline levels of prolactin or corticosterone. On the other hand, short-term but not long-term lithium treatment significantly increased baseline levels of corticosterone but not of prolactin. Short-term treatment with lithium but not clorgyline or imipramine potentiated fenfluramine-induced increases in plasma prolactin but not corticosterone. On the other hand, long-term treatment with clorgyline but not imipramine or lithium attenuated fenfluramine's effect on plasma prolactin but not on corticosterone. These findings demonstrate differential effects of antidepressant treatments on fenfluramine-induced increases in plasma prolactin and corticosterone in rats and are consistent with several other clinical and animal studies demonstrating dissimilar actions of different antidepressant treatments on two different 5-HT-mediated neuroendocrine functions. RP AULAKH, CS (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,ROOM 3D41,BETHESDA,MD 20892, USA. NR 58 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 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 1991 VL 39 IS 1 BP 91 EP 95 DI 10.1016/0091-3057(91)90402-N PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA FT789 UT WOS:A1991FT78900015 PM 1924518 ER PT J AU KEDAR, PS WIDEN, SG ENGLANDER, EW FORNACE, AJ WILSON, SH AF KEDAR, PS WIDEN, SG ENGLANDER, EW FORNACE, AJ WILSON, SH TI THE ATF CREB TRANSCRIPTION FACTOR-BINDING SITE IN THE POLYMERASE-BETA PROMOTER MEDIATES THE POSITIVE EFFECT OF N-METHYL-N'-NITRO-N-NITROSOGUANIDINE ON TRANSCRIPTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-DAMAGING AGENTS; HUMAN-CELLS; REGULATORY ELEMENTS; MAMMALIAN-CELLS; MESSENGER-RNA; C-FOS; GENE; REPAIR; PROTEIN; UV AB DNA polymerase-beta (pol-beta) is a constitutively expressed DNA repair enzyme in vertebrate cells. Yet, it had been shown previously that the pol-beta mRNA level increases in Chinese hamster ovary (CHO) cells within 4 h after treatment with several monofunctional DNA damaging agents, notably, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Herein we report that a transfected pol-beta-promoter fusion gene is activated by MNNG treatment of CHO cells; mRNA from the transfected gene is almost-equal-to 10-fold higher in treated cells than in untreated cells 16 h after treatment. This activation is mediated through the decanucleotide palindromic element GTGACGTCAC at positions -49 to -40 in the "TATA-less" core promoter. This element, which is similar to the ATF/CREB transcription factor-binding site in a number of mammalian genes, forms the center of a strong protein-binding site for CHO cell nuclear extract proteins. Mutated pol-beta-promoter fusion genes lacking the element fail to bind protein at this site and fail to respond to MNNG treatment of cells. C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP KEDAR, PS (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 32 TC 53 Z9 53 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 9 BP 3729 EP 3733 DI 10.1073/pnas.88.9.3729 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FK184 UT WOS:A1991FK18400046 PM 1827204 ER PT J AU PATERSON, BM WALLDORF, U ELDRIDGE, J DUBENDORFER, A FRASCH, M GEHRING, WJ AF PATERSON, BM WALLDORF, U ELDRIDGE, J DUBENDORFER, A FRASCH, M GEHRING, WJ TI THE DROSOPHILA HOMOLOG OF VERTEBRATE MYOGENIC-DETERMINATION GENES ENCODES A TRANSIENTLY EXPRESSED NUCLEAR-PROTEIN MARKING PRIMARY MYOGENIC CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INSECT MYOGENESIS; HELIX-LOOP-HELIX; INVERTEBRATE MYOD ID GERM-LAYER; FIBROBLASTS; MYOBLASTS; MYOD1; SEQUENCE; ELEMENTS; MARKERS; EMBRYOS; DNA AB We have isolated a cDNA clone, called Dmyd for Drosophila myogenic-determination gene, that encodes a protein with structural and functional characteristics similar to the members of the vertebrate MyoD family. Dmyd clone encodes a polypeptide of 332 amino acids with 82% identity to MyoD in the 41 amino acids of the putative helix-loop-helix region and 100% identity in the 13 amino acids of the basic domain proposed to contain the essential recognition code for muscle-specific gene activation. Low-stringency hybridizations indicate that Dmyd is not a member of a multigene family similar to MyoD in vertebrates. Dmyd is a nuclear protein in Drosophila, consistent with its role as a nuclear-gene regulatory factor, and is proposed to be a transiently expressed marker for muscle founder cells. We have used an 8-kilobase promoter fragment from the gene, which contains the first 55 amino acids of the Dmyd protein, joined to lacZ, to follow myogenic precursor cells into muscle fibers with antibodies to beta-galactosidase and to Dmyd. Unlike the myogenic factors in vertebrate muscle cells, Dmyd appears to be expressed at a much lower level in differentiated Drosophila muscles, so Dmyd cannot be followed continuously as a muscle marker. This fact is reflected in the loss of Dmyd RNA expression in 12- to 24-hr embryos, a major period of early myogenesis, as well as in the undetectable level of the nuclear antigen in primary cultures of embryonic and adult Drosophila muscle. C1 UNIV BASEL,BIOCTR,DEPT CELL BIOL,CH-4056 BASEL,SWITZERLAND. UNIV ZURICH,INST ZOOL,CH-8057 ZURICH,SWITZERLAND. MAX PLANCK INST DEV BIOL,GENET ABT 3,W-7400 TUBINGEN,GERMANY. RP PATERSON, BM (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. RI Frasch, Manfred/H-7002-2013 OI Frasch, Manfred/0000-0003-1373-9798 NR 35 TC 123 Z9 124 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 9 BP 3782 EP 3786 DI 10.1073/pnas.88.9.3782 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FK184 UT WOS:A1991FK18400057 PM 1902570 ER PT J AU CRUCIANI, RA BARKER, JL ZASLOFF, M CHEN, HC COLAMONICI, O AF CRUCIANI, RA BARKER, JL ZASLOFF, M CHEN, HC COLAMONICI, O TI ANTIBIOTIC MAGAININS EXERT CYTOLYTIC ACTIVITY AGAINST TRANSFORMED-CELL LINES THROUGH CHANNEL FORMATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTITUMOR; CYTOLYSIS; MAGAININ CHANNELS ID ANTIMICROBIAL ACTIVITY; PEPTIDE MAGAININ-2; XENOPUS SKIN; ANALOGS; FORMS AB Magainins are an ionophoric class of vertebrate peptides with antibiotic activity against various microorganisms. Here we show that magainin 2 and synthetic analogues can rapidly and irreversibly lyse hematopoietic tumor and solid tumor target cells with a relative cytotoxic potency that parallels their antibacterial efficacy and at concentrations that are relatively nontoxic to well-differentiated cells. The cytotoxicity is prevented by cell depolarization. Magainins represent a natural cytolytic agent in vertebrates and may provide another therapeutic strategy for certain tumors. C1 NINCDS,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. CHILDRENS HOSP PHILADELPHIA,DEPT GENET,DIV HUMAN GENET,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DEPT PEDIAT,PHILADELPHIA,PA 19104. UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637. NR 14 TC 298 Z9 311 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 9 BP 3792 EP 3796 DI 10.1073/pnas.88.9.3792 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FK184 UT WOS:A1991FK18400059 PM 1708887 ER PT J AU HACKSTADT, T BAEHR, W YING, Y AF HACKSTADT, T BAEHR, W YING, Y TI CHLAMYDIA-TRACHOMATIS DEVELOPMENTALLY REGULATED PROTEIN IS HOMOLOGOUS TO EUKARYOTIC HISTONE H1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OUTER-MEMBRANE PROTEIN; BINDING PROTEINS; GENE; CYCLE; IDENTIFICATION; COMPONENTS; EXPRESSION; ENVELOPES; PSITTACI; DOMAINS AB Chlamydiae are prokaryotic obligate intracellular parasites that undergo a biphasic life cycle involving an infectious, extracellular form known as elementary bodies and an intracellular, replicating form termed reticulate bodies. We have purified from Chlamydia trachomatis a very basic elementary body-specific protein with an apparent molecular mass of 18 kDa, determined its N-terminal amino acid sequence, and cloned the encoding gene. Sequence analysis of the cloned gene revealed some remarkable properties for its expressed product, including a high lysine content (29%), a correspondingly high pI, and significant homology to the H-1 class of eukaryotic histones. Furthermore, a monoclonal antibody to this chlamydial histone analog, termed Hc1, displayed immunoblot and antinuclear specificity suggestive of cross-reactivity to H-1 histones. The gene was expressed only during the late stages of the chlamydial life cycle concomitant with the reorganization of chlamydial reticulate bodies into elementary bodies, suggesting that the Hc1 protein plays a role in the condensation of chlamydial chromatin during intracellular differentiation. C1 UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77550. UNIV TEXAS,MED BRANCH,DEPT MICROBIOL,GALVESTON,TX 77550. BAYLOR UNIV,DEPT OPHTHALMOL,HOUSTON,TX 77030. RP HACKSTADT, T (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. NR 32 TC 105 Z9 106 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 9 BP 3937 EP 3941 DI 10.1073/pnas.88.9.3937 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FK184 UT WOS:A1991FK18400088 PM 2023942 ER PT J AU BECKER, PB RABINDRAN, SK WU, C AF BECKER, PB RABINDRAN, SK WU, C TI HEAT SHOCK-REGULATED TRANSCRIPTION INVITRO FROM A RECONSTITUTED CHROMATIN TEMPLATE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NUCLEOSOME ASSEMBLY; GENERAL TRANSCRIPTION FACTOR-IID; HEAT SHOCK FACTOR ID RNA POLYMERASE-II; IMMEDIATE EARLY PROTEIN; SIMIAN VIRUS 40; TATA-BOX; DROSOPHILA-MELANOGASTER; BINDING-PROTEIN; GENE PROMOTERS; HSP70 GENE; MAJOR LATE; YEAST AB To investigate the mechanisms of transcriptional regulation of Drosophila heat shock genes we studied the activity of a heat shock promoter in vitro after reconstitution into chromatin. Increasing the duration of nucleosome assembly progressively inactivated a plasmid template when it was transcribed with extracts of either unshocked or heat-shocked Drosophila embryos, despite induction of the transcriptional activator heat shock factor. Addition of the general transcription factor IID (TFIID) before nucleosome assembly did not significantly relieve nucleosomal inhibition, but TFIID potentiated the promoter to be responsive to activation by heat shock factor in the heat shock transcription extract. The potentiation by TFIID could be related to the nucleosome-free, hypersensitive state of heat shock promoters previously observed in vivo before heat shock induction and may be necessitated by the need to expediate activation of heat shock genes in response to environmental stress. RP BECKER, PB (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 49 TC 57 Z9 58 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 10 BP 4109 EP 4113 DI 10.1073/pnas.88.10.4109 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM042 UT WOS:A1991FM04200011 PM 2034656 ER PT J AU TEKLE, E ASTUMIAN, RD CHOCK, PB AF TEKLE, E ASTUMIAN, RD CHOCK, PB TI ELECTROPORATION BY USING BIPOLAR OSCILLATING ELECTRIC-FIELD - AN IMPROVED METHOD FOR DNA TRANSFECTION OF NIH 3T3 CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENE TRANSFECTION; ELECTROPERMEABILIZATION ID HIGH-EFFICIENCY TRANSFORMATION; GENE-TRANSFER; MAMMALIAN-CELLS; INTACT YEAST; ELECTROPERMEABILIZATION; PROTOPLASTS; EXPRESSION; MEMBRANES AB Using the plasmid DNA pSV2-neo (which, when integrated into the cellular genome confers resistance to the antibiotic G418 for selection), we examined and compared the transfection efficiency on NIH 3T3 cells electro-permeabilized by applying a sequence of high-frequency unipolar or bipolar square waves or a single square pulse. Results show that a bipolar square wave is, at least, 1.7- and 5.5-fold more efficient than the unipolar square wave and single square pulse, respectively. In the range of electric field strength used for optimum transfection, the survivability of electro-permeabilized cells was comparable between the unipolar and bipolar square waves but fell considerably with the single square pulse. Qualitative comparison of cell permeabilization induced by the three types of wave forms and monitored by ethidium bromide uptake revealed that only the bipolar square wave permeabilizes the cell membrane symmetrically at the two hemispheres facing the electrodes. With unipolar square wave or single square pulse, the membrane is permeabilized either on one side or asymmetrically. Taken together, our results suggests that permeabilization of the membrane at multiple sites without affecting cell survivability may account for the improvements in transfection efficiency observed with bipolar oscillating electric fields. C1 NATL INST STAND & TECHNOL,DIV BIOTECHNOL,GAITHERSBURG,MD 20899. RP TEKLE, E (reprint author), NHLBI,BIOCHEM LAB,METAB REGULAT SECT,BLDG 3,ROOM 203,BETHESDA,MD 20892, USA. NR 28 TC 120 Z9 124 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 10 BP 4230 EP 4234 DI 10.1073/pnas.88.10.4230 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM042 UT WOS:A1991FM04200036 PM 2034667 ER PT J AU FUJII, Y MOREIRA, JE ORLANDO, C MAGGI, M AURBACH, GD BRANDI, ML SAKAGUCHI, K AF FUJII, Y MOREIRA, JE ORLANDO, C MAGGI, M AURBACH, GD BRANDI, ML SAKAGUCHI, K TI ENDOTHELIN AS AN AUTOCRINE FACTOR IN THE REGULATION OF PARATHYROID CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VASCULAR SMOOTH-MUSCLE; PROTEIN KINASE-C; ATRIAL NATRIURETIC PEPTIDE; CULTURED MESANGIAL CELLS; MESSENGER-RNA; VASOCONSTRICTOR PEPTIDE; CALCIUM CHANNELS; BIOLOGICAL-ACTIVITY; CELLULAR MECHANISM; DOWN-REGULATION AB Endothelin, originally purified from porcine aortic endothelial cells, is widely distributed in tissues and is recognized as a product of epithelial cells, glial cells, and neurons in addition to endothelial cells. We found evidence by mRNA content and immunoreactivity that this peptide is synthesized in rat parathyroid epithelial cells (PT-r cells) and bovine parathyroid chief cells. The peptide synthesized by PT-r cells comigrated with synthetic endothelin 1 in reverse-phase HPLC and was diluted out in radioimmunoassay in parallel with the synthetic peptide. Bovine parathyroid endothelial cells (BPE-1 cells) did not express this peptide. Preproendothelin 1 mRNA expression by PT-r cells and endothelin 1 peptide production were regulated by calcium. Shifts in extracellular calcium either from high to low concentrations or vice versa elicited similar evanescent increases in expression of mRNA with a peak at 1 h. Synthesis of the peptide seems to be controlled by mRNA expression, and peptide in the medium appears to be continuously degraded or taken up by cells because its concentration in the medium showed a time course similar to that of mRNA expression. PT-r cells also bear a single class of receptors highly specific for endothelin 1, suggesting an autocrine regulation by endothelin 1 of the parathyroid. The facile regulation of endothelin concentrations in the medium by shifts in extracellular calcium concentration and possible autocrine regulation by endothelin 1 suggest that this peptide may mediate, at least in part, effects of calcium on the parathyroid system. C1 NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NINCDS,NEUROBIOL LAB,BETHESDA,MD 20892. UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,I-50121 FLORENCE,ITALY. NR 73 TC 75 Z9 75 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 10 BP 4235 EP 4239 DI 10.1073/pnas.88.10.4235 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM042 UT WOS:A1991FM04200037 PM 1852000 ER PT J AU ONO, SJ BAZIL, V LEVI, BZ OZATO, K STROMINGER, JL AF ONO, SJ BAZIL, V LEVI, BZ OZATO, K STROMINGER, JL TI TRANSCRIPTION OF A SUBSET OF HUMAN CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX GENES IS REGULATED BY A NUCLEOPROTEIN COMPLEX THAT CONTAINS C-FOS OR AN ANTIGENICALLY RELATED PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HLA; LEUCINE ZIPPER PROTEINS; ANTISENSE RNA ID PROMOTER BINDING-PROTEIN; HLA-DR; CELL-LINES; DIFFERENTIAL EXPRESSION; LEUCINE ZIPPER; PHORBOL ESTER; HEAVY-CHAIN; FACTOR AP-1; JUN; ORGANIZATION AB Transcriptional regulation of the human major histocompatibility complex class II genes requires at least two upstream elements, the X and Y boxes, located in the -50- to -150-base-pair region of all class II promoters. The DRA and DPB promoters contain phorbol ester-responsive elements overlapping the 3' side of their X boxes. Mutation of this sequence down-regulates the efficiency of the DRA promoter, suggesting that a positive regulator(s) binds to this site. In this report, anti-sense c-fos RNA and an anti-c-fos antibody were used to show that the product of the protooncogene c-fos or an antigenically related protein is a component of a complex that binds to the X box and is required for maximal transcription from the DRA and DPB promoters. As c-fos (or its related proteins) cannot bind alone to DNA, these results suggest that it may dimerize with other members of the JUN/AP-1 family, such as hXBP1, to participate in the activation of a subset of class II major histocompatibility complex genes. C1 NICHHD,DEV & MOLEC IMMUN LAB,MOLEC GENET IMMUN SECT,BETHESDA,MD 20892. RP ONO, SJ (reprint author), HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,7 DIV AVE,CAMBRIDGE,MA 02138, USA. FU NCI NIH HHS [CA-47554]; NIDDK NIH HHS [DK-30241, DK-13230] NR 45 TC 51 Z9 51 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 10 BP 4304 EP 4308 DI 10.1073/pnas.88.10.4304 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM042 UT WOS:A1991FM04200051 PM 1709740 ER PT J AU TOLEDANO, MB LEONARD, WJ AF TOLEDANO, MB LEONARD, WJ TI MODULATION OF TRANSCRIPTION FACTOR NF-KAPPA-B BINDING-ACTIVITY BY OXIDATION REDUCTION INVITRO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DIAMIDE; N-ETHYLMALEIMIDE; 2-MERCAPTOETHANOL; AP-1; SERUM RESPONSE FACTOR ID HUMAN-IMMUNODEFICIENCY-VIRUS; SERUM RESPONSE ELEMENT; C-FOS; INDUCIBLE GENES; ACTIVATION; PROTEIN; INTERLEUKIN-2; IDENTIFICATION; PURIFICATION; LYMPHOCYTES AB NF-kappa-B is a widely used regulator of inducible and tissue-specific gene control. In the cytosol, when complexed to an inhibitory molecule, I-kappa-B, NF-kappa-B is in an inactive form and cannot bind DNA. Activation of cells with appropriate stimuli results in the dissociation of NF-kappa-B from I-kappa-B and its translocation to the nucleus as an active binding protein. We now demonstrate that NF-kappa-B binding in vitro can be inhibited by agents that modify free sulfhydryls. Binding is eliminated after treatment with N-ethylmaleimide, an alkylating agent, and diamide, an oxidizing agent. The diamide effect can be reversed by 2-mercaptoethanol. Further, 2-mercaptoethanol acts synergistically with deoxycholate plus Nonidet P-40 in converting inactive cytosolic NF-kappa-B to an active DNA-binding form. It is therefore possible that modulation of the redox state of NF-kappa-B could represent a post-translational control mechanism for this factor. RP TOLEDANO, MB (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 40 TC 562 Z9 566 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 10 BP 4328 EP 4332 DI 10.1073/pnas.88.10.4328 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM042 UT WOS:A1991FM04200056 PM 1903539 ER PT J AU EATON, WA HENRY, ER HOFRICHTER, J AF EATON, WA HENRY, ER HOFRICHTER, J TI APPLICATION OF LINEAR FREE-ENERGY RELATIONS TO PROTEIN CONFORMATIONAL-CHANGES - THE QUATERNARY STRUCTURAL-CHANGE OF HEMOGLOBIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE KINETICS; DYNAMICS; TRANSITION STATE THEORY; REACTION PATH; ALLOSTERY ID LIGAND-BINDING; LASER PHOTOLYSIS; CARBON-MONOXIDE; TROUT-I; COOPERATIVITY; KINETICS; STEREOCHEMISTRY; MECHANISMS; MODEL AB The transition state for the R arrow pointing right over arrow pointing left T quaternary conformational change of hemoglobin has thermodynamic properties much closer to those of the R conformation than to those of the T conformation. This finding is based on a comparison of activation and equilibrium enthalpy and entropy changes and on the observation of a linear free energy relationship between quaternary rate and equilibrium constants. A previous theoretical study [Janin, J. & Wodak, S. J. (1985) Biopolymers 24, 509-526], using a highly simplified energy function, suggests that the R-like transition state is the result of a reaction pathway with the maximum buried surface area between alpha-beta-dimers. RP EATON, WA (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 38 TC 59 Z9 59 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 10 BP 4472 EP 4475 DI 10.1073/pnas.88.10.4472 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM042 UT WOS:A1991FM04200086 PM 2034685 ER PT J AU LOPEZ, FJ MERCHENTHALER, I CHING, M WISNIEWSKI, MG NEGROVILAR, A AF LOPEZ, FJ MERCHENTHALER, I CHING, M WISNIEWSKI, MG NEGROVILAR, A TI GALANIN - A HYPOTHALAMIC-HYPOPHYSIOTROPIC HORMONE MODULATING REPRODUCTIVE FUNCTIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LUTEINIZING HORMONE-RELEASING HORMONE; PORTAL BLOOD; NEUROSECRETION ID CENTRAL NERVOUS-SYSTEM; GROWTH-HORMONE; ANTERIOR-PITUITARY; RAT GALANIN; SECRETION; RELEASE; INVITRO; BRAIN; LH; INVOLVEMENT AB Galanin (GAL) is widely distributed in the peripheral and the central nervous systems. In the brain, the highest GAL concentrations are observed within the hypothalamus and, particularly, in nerve terminals of the median eminence. This location, as well as GAL actions on prolactin, growth hormone, luteinizing hormone (LH), and LH-releasing hormone (LHRH) secretion, suggest the possibility that GAL may act as a putative hypothalamic-hypophysiotropic hormone. To establish this, GAL and LHRH levels were measured in hypophyseal portal plasma samples using specific radioimmunoassays. Rat galanin (rGAL) concentrations in portal blood were almost-equal-to 7-fold hiher than those observed in peripheral plasma in male and female (estrus, diestrus) rats, indicating an active secretory process of rGAL into the portal vasculature. Frequent (10 min) sampling revealed that rGAL and LHRH were secreted into the portal circulation in a pulsatile manner with a pulse frequency of one pulse per hour. Interestingly, both hormone series depicted a high degree of coincident episodes. In fact, the probability of random coincidence, calculated by the algorithm HYPERGEO, was < 0.01. Moreover, the retrograde tracer Fluoro-Gold, when given systemically, was taken up by GAL neurons in the hypothalamus, including a subset of neurons expressing rGAL and LHRH, strengthening the notion of the existence of a GAL neuronal system connected to the hypophyseal portal circulation. These observations reinforce the concept that GAL regulates pituitary hormone secretion. To analyze this in further detail, the effects of rGAL on LH secretion were evaluated under basal and stimulated conditions. rGAL induced a small but dose-dependent increase in LH secretion from cultured, dispersed pituitary cells. Interestingly, rGAL enhanced the ability of LHRH to stimulate LH release. The tight link between GAL and LHRH neuronal systems is strengthened by the observation that during the estrous cycle of the rat, rGAL and LHRH contents in the median eminence show an identical profile (r = 1.00). These data indicate that GAL should be considered as a hypothalamic-hypophysiotropic hormone and as an important neuromodulator of LHRH secretion and action. The colocalization and cosecretion of GAL and LHRH and the cooperative action at the level of the anterior pituitary afford important evidence for the functional significance of coexistence of neurotransmitters in neurons of the central nervous system. C1 NIEHS,MOLEC & INTEGRAT LAB,FUNCT MORPHOL SECT,RES TRIANGLE PK,NC 27709. RP LOPEZ, FJ (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 163 Z9 166 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 10 BP 4508 EP 4512 DI 10.1073/pnas.88.10.4508 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM042 UT WOS:A1991FM04200094 PM 1709744 ER PT J AU KANESHIMA, H SHIH, CC NAMIKAWA, R RABIN, L OUTZEN, H MACHADO, SG MCCUNE, JM AF KANESHIMA, H SHIH, CC NAMIKAWA, R RABIN, L OUTZEN, H MACHADO, SG MCCUNE, JM TI HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION OF HUMAN LYMPH-NODES IN THE SCID-HU MOUSE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANIMAL MODEL; NATURAL TROPISM; VIREMIA; DRUG TESTING; DOSE-RESPONSE ID CONTROLLED TRIAL; HIV-INFECTION; HTLV-III; AIDS; RETROVIRUS; INVIVO; CELLS; LAV; AZT AB The SCID-hu mouse is a small animal in which human hematolymphoid organs can be engrafted and maintained in vivo. In this study, parameters are described for reproducible infection of SCID-hu mice after i.v. inoculation. Infection was found to be dependent upon the time after inoculation, the virus isolate, the titer of virus, and the human target organ implanted into the mouse. Ten to 14 days after the i.v. administration of HIV isolates derived freshly from patients (e.g., JR-CSF, JR-FL, SM), 100% of engrafted human lymph nodes in SCID-hu mice were infected; > 95% of these animals were also viremic. Implants of human thymus or connective tissue, as well as the endogenous murine hematolymphoid organs, were not infected. As demonstrated by a combination of in situ hybridization and immunohistochemistry, both T-lymphoid and myelomonocytic lineage cells were infected in this system. HIV isolates that have been adapted to growth in vitro (e.g., HTLV-IIIb) were not infectious. When either 3'-azido-3'-deoxythymidine (AZT) or 2',3'-dideoxyinosine (ddIno) was administered to SCID-hu mice before HIV infection, the animals were protected in dose ranges similar to those used in man. This animal model may now be used as an efficient intermediate step between the lab and the clinic to study the infectious process in vivo and to best select efficacious antiviral compounds against HIV. C1 NIAID,DIV AIDS,BETHESDA,MD 20892. RP KANESHIMA, H (reprint author), SYSTEMIX INC,HIV GRP,PALO ALTO,CA 94303, USA. FU NIAID NIH HHS [R0-AI-29323] NR 24 TC 72 Z9 72 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 10 BP 4523 EP 4527 DI 10.1073/pnas.88.10.4523 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM042 UT WOS:A1991FM04200097 PM 1903543 ER PT J AU PURDY, RH MORROW, AL MOORE, PH PAUL, SM AF PURDY, RH MORROW, AL MOORE, PH PAUL, SM TI STRESS-INDUCED ELEVATIONS OF GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTOR-ACTIVE STEROIDS IN THE RAT-BRAIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ALLOPREGNANOLONE; ALLOTETRAHYDRODEOXYCORTICOSTERONE; ENDOGENOUS LIGANDS; GABA-A RECEPTORS; STRESS ID BENZODIAZEPINE RECEPTORS; PROGESTERONE METABOLITE; GABAA RECEPTOR; 3-ALPHA-HYDROXY-5-ALPHA-PREGNAN-20-ONE; MODULATION; PREGNENOLONE; CHOLESTEROL; SECRETION; COMPLEX; CELLS AB A 3-alpha-hydroxy A-ring-reduced metabolite of progesterone, 3-alpha-hydroxy-5-alpha-pregnan-20-one (allopregnanolone), and one of deoxycorticosterone (DOC), 3-alpha,21-dihydroxy-5-alpha-pregnan-20-one (allotetrahydroDOC), are among the most potent known ligands of gamma-aminobutyric acid (GABA) receptors designated GABA(A) in the central nervous system. With specific radioimmunoassays, rapid (< 5 min) and robust (4- to 20-fold) increases of allopregnanolone and allotetrahydroDOC were detected in the brain (cerebral cortex and hypothalamus) and in plasma of rats after exposure to ambient temperature swim stress. Neither steroid was detectable in the plasma of adrenalectomized rats either before or after swim stress. However, allopregnanolone, but not allotetrahydroDOC, was still present in the cerebral cortex (> 3 ng/g) after adrenalectomy. These data demonstrate the presence of allopregnanolone and allotetrahydroDOC in brain and show that acute stress results in a rapid increase of these neuroactive steroids to levels known to modulate GABA(A) receptor function. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RP PURDY, RH (reprint author), SW FDN BIOMED RES,DEPT ORGAN CHEM,SAN ANTONIO,TX 78284, USA. NR 41 TC 701 Z9 713 U1 2 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY PY 1991 VL 88 IS 10 BP 4553 EP 4557 DI 10.1073/pnas.88.10.4553 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FM042 UT WOS:A1991FM04200103 PM 1852011 ER PT J AU JOHNSON, MD MCMILLIAN, MK SCHANBERG, SM AF JOHNSON, MD MCMILLIAN, MK SCHANBERG, SM TI ALTERATIONS IN CARDIOVASCULAR RESPONSIVENESS AND ADRENOCEPTOR BINDING DURING CATECHOLAMINE INFUSION HYPERTENSION IN RATS SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID ORNITHINE DECARBOXYLASE ACTIVITY; SMOOTH-MUSCLE CONTRACTION; SYMPATHETIC ACTIVITY; NOREPINEPHRINE SENSITIVITY; HARBORING PHEOCHROMOCYTOMA; IMMOBILIZATION STRESS; ADRENERGIC-RECEPTORS; REPEATED INJECTION; GROWTH-HORMONE; DESENSITIZATION AB Chronic continuous infusion of norepinephrine in rats causes alterations in biochemical and physiologic responses of the cardiovascular system and in cardiovascular adrenoceptor number. The response of cardiac and aortic ornithine decarboxylase (ODC) activity to stimulation by norepinephrine was decreased in rats receiving norepinephrine infusion. These responses are due to stimulation of beta- and alpha-adrenergic receptors, respectively. Additionally, there was reduced stimulation of aortic ODC activity by angiotensin II and vasopressin. The cardiac ODC response to angiotensin II was decreased, but the response to vasopressin was not affected. The decreased ODC response is accompanied by decreased pressor responses to the alpha-adrenergic agonist phenylephrine. Decreased numbers of alpha- and beta-adrenoceptor binding sites (as measured by the binding of [H-3]prazosin and [I-125]pindolol) might mediate, in part, the altered responses to adrenergic agonists. The decreased cardiovascular responsiveness measured in these animals after several days of norepinephrine infusion hypertension contrasts with the increased responses found in most other forms of hypertension. This provides a useful model in which to examine the consequences of prolonged adrenergic receptor stimulation. C1 NIEHS,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. RP JOHNSON, MD (reprint author), MED COLL PENN,EASTERN PENN PSYCHIAT INST,DEPT PHARMACOL,3200 HENRY AVE,PHILADELPHIA,PA 19129, USA. FU NIMH NIH HHS [MH13688-24] NR 37 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAY PY 1991 VL 197 IS 1 BP 67 EP 73 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FK094 UT WOS:A1991FK09400011 PM 1850525 ER PT J AU PARRY, BL ROSENTHAL, NE JAMES, SP WEHR, TA AF PARRY, BL ROSENTHAL, NE JAMES, SP WEHR, TA TI ATENOLOL IN PREMENSTRUAL-SYNDROME - A TEST OF THE MELATONIN HYPOTHESIS SO PSYCHIATRY RESEARCH LA English DT Article DE ATENOLOL; PREMENSTRUAL SYNDROME; LIGHT THERAPY; MELATONIN ID SEASONAL AFFECTIVE-DISORDER; PHASE DYSPHORIC DISORDER; LIGHT; DEPRESSION; SECRETION; PLASMA; ANTIDEPRESSANT; RHYTHM; URINE AB Eleven patients with prospectively documented premenstrual depression were given 100 mg atenolol or placebo daily to suppress melatonin secretion during the symptomatic premenstrual phase of the menstrual cycle. There was no significant improvement in mood following treatment with atenolol vs. placebo. These findings suggest that bright light may exert antidepressant effects in patients with premenstrual syndrome through mechanisms other than melatonin suppression and that atenolol does not appear to be a viable treatment modality for the majority of patients with premenstrual depression. C1 NIMH,CLIN PSYCHOBIOL BRANCH,OUTPATIENT RES PROGRAM,BETHESDA,MD 20892. YORBA HILLS HOSP & MED CTR,YORBA LINDA,CA. RP PARRY, BL (reprint author), UNIV CALIF SAN DIEGO,PSYCHIAT,T-004,LA JOLLA,CA 92093, USA. FU NCRR NIH HHS [MO1 RR-00827]; NIMH NIH HHS [R29 MH-42831] NR 31 TC 7 Z9 7 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY PY 1991 VL 37 IS 2 BP 131 EP 138 DI 10.1016/0165-1781(91)90070-6 PG 8 WC Psychiatry SC Psychiatry GA FU455 UT WOS:A1991FU45500002 PM 1876626 ER PT J AU SWANN, AC SECUNDA, SK KOSLOW, SH KATZ, MM BOWDEN, CL MAAS, JW DAVIS, JM ROBINS, E AF SWANN, AC SECUNDA, SK KOSLOW, SH KATZ, MM BOWDEN, CL MAAS, JW DAVIS, JM ROBINS, E TI MANIA - SYMPATHOADRENAL FUNCTION AND CLINICAL STATE SO PSYCHIATRY RESEARCH LA English DT Article DE MANIA; MIXED AFFECTIVE STATE; EPINEPHRINE; NOREPINEPHRINE; BEHAVIOR ID MONOAMINE METABOLITES; DEPRESSION; DIAGNOSIS; CSF AB We investigated sympathoadrenal and sympathetic nervous system activity, catecholamine disposition, and clinical state in 19 hospitalized manic patients. Severity of the core manic syndrome, anxiety, and hostility correlated with 24-hour urinary excretion of epinephrine relative to its metabolites,but only weakly with norepinephrine. Agitation, however, correlated most strongly and significantly with norepinephrine. Eight of the patients had mixed states: concurrent manic and depressive syndromes. There were no differences between mixed and pure manic patients with respect to catecholamine or metabolite excretion or precursor/product ratios, but mixed manic patients tended to have higher excretion of norepinephrine and had increased variance with respect to catecholamine measures. These data suggest that the function of the adrenal medulla, whether directly or indirectly, is important in the symptoms of both mixed and pure mania. C1 NIMH,SPRINGFIELD,PA 19064. NIMH,DIV BASIC SCI,ROCKVILLE,MD 20857. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX MUNICIPAL HOSP,DEPT PSYCHIAT,BRONX,NY 10461. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. ILLINOIS STATE PSYCHIAT INST,RES,CHICAGO,IL 60612. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. RP SWANN, AC (reprint author), UNIV TEXAS,SCH MED,DEPT PSYCHIAT,POB 20708,HOUSTON,TX 77225, USA. FU NIMH NIH HHS [MH-38084, MH-26975, MH-26977] NR 34 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY PY 1991 VL 37 IS 2 BP 195 EP 205 DI 10.1016/0165-1781(91)90075-Z PG 11 WC Psychiatry SC Psychiatry GA FU455 UT WOS:A1991FU45500007 PM 1876629 ER PT J AU SCHEFFERS, MK JOHNSON, R RUCHKIN, DS AF SCHEFFERS, MK JOHNSON, R RUCHKIN, DS TI P300 IN PATIENTS WITH UNILATERAL TEMPORAL LOBECTOMIES - THE EFFECTS OF REDUCED STIMULUS QUALITY SO PSYCHOPHYSIOLOGY LA English DT Article DE P300; NEURAL GENERATORS; TEMPORAL LOBECTOMY PATIENTS; EQUIVOCATION; P300 ONSET AND DURATION ID EVENT-RELATED POTENTIALS; HUMAN HIPPOCAMPAL-FORMATION; MENTAL CHRONOMETRY; INFORMATION; COMPONENTS; PSYCHOPHYSIOLOGY; DISCRIMINATION; GENERATORS; AMPLITUDE; SCALP AB The effects of stimulus quality on the amplitude, peak latency, onset latency, and duration of the P300 component of the event-related brain potential were studied in patients with either a left or a right anterior temporal lobectomy and in normal controls. Stimulus quality was reduced by adding "noise" letters to words which signalled either a left or a right hand button press. Consistent with an interpretation that stimulus quality affects the subject's degree of equivocation, P300 peak latency, reaction time, and errors were all inversely related to stimulus quality, whereas P300 amplitude was directly related to stimulus quality. There were no significant differences between normal controls and either patient group for any of the ERP parameters or reaction time. Right temporal lobectomy patients made, however, significantly more errors, particularly on the catch trials, which suggests that they did not process the stimuli as thoroughly and accurately as the subjects in the other two groups. The absence of significant group differences in either the lateral symmetry or overall P300 amplitude extends the evidence against the idea that anterior temporal lobe structures make any substantial contribution to the scalp P300 in a visual discrimination paradigm. Because of observed delays in the onset of P300 in the low-quality stimulus condition, procedures were developed to quantify both P300 onset latency and P300 duration. Reduced stimulus quality significantly increased P300 onset latency whereas P300 duration remained unaffected, indicating that stimulus categorization must occur prior to, and not during, P300. C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 5C422,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. FU NINDS NIH HHS [NS11199] NR 43 TC 25 Z9 25 U1 0 U2 0 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAY PY 1991 VL 28 IS 3 BP 274 EP 284 DI 10.1111/j.1469-8986.1991.tb02194.x PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA GD534 UT WOS:A1991GD53400003 PM 1946893 ER PT J AU FRASER, DD FRANK, JA DALAKAS, MC AF FRASER, DD FRANK, JA DALAKAS, MC TI INFLAMMATORY MYOPATHIES - MR IMAGING AND SPECTROSCOPY SO RADIOLOGY LA English DT Editorial Material DE DERMATOMYOSITIS; MAGNETIC RESONANCE (MR), PHOSPHORUS STUDIES; MAGNETIC RESONANCE (MR), SPECTROSCOPY; MUSCLES, DISEASES; MUSCLES, MR STUDIES C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. RP FRASER, DD (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BLDG 10,RM 9N244,BETHESDA,MD 20892, USA. NR 7 TC 22 Z9 22 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1991 VL 179 IS 2 BP 341 EP 342 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FH130 UT WOS:A1991FH13000007 PM 2064655 ER PT J AU WALSH, TJ LEE, J LECCIONES, J RUBIN, M BUTLER, K FRANCIS, P WEINBERGER, M ROILIDES, E MARSHALL, D GRESS, J PIZZO, PA AF WALSH, TJ LEE, J LECCIONES, J RUBIN, M BUTLER, K FRANCIS, P WEINBERGER, M ROILIDES, E MARSHALL, D GRESS, J PIZZO, PA TI EMPIRIC THERAPY WITH AMPHOTERICIN-B IN FEBRILE GRANULOCYTOPENIC PATIENTS SO REVIEWS OF INFECTIOUS DISEASES LA English DT Article ID INVASIVE PULMONARY ASPERGILLOSIS; CANCER-PATIENTS; FUNGAL-INFECTIONS; ACUTE-LEUKEMIA; DISSEMINATED CANDIDIASIS; HEPATIC CANDIDIASIS; ANTIFUNGAL THERAPY; FEVER; MANAGEMENT; DIAGNOSIS AB The early diagnosis of invasive fungal infection in granulocytopenic patients remains unreliable. Granulocytopenic patients who are persistently or recurrently febrile despite therapy with appropriate antibacterial agents are at high risk for the development of such infection. Two randomized clinical trials demonstrated that the empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients decreased the frequency, morbidity, and mortality of invasive fungal infection; these effects were especially marked in profoundly granulocytopenic patients who were not receiving antifungal prophylaxis. Current studies continue to indicate that prompt empiric administration of amphotericin B to persistently or recurrently febrile granulocytopenic patients ensures earlier treatment of deep mycoses. The roles of newer antifungal triazole compounds and of liposomal and lipid complexes of amphotericin B in empiric antifungal therapy must be investigated further in thoughtfully designed, randomized clinical trials. RP WALSH, TJ (reprint author), NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,ROOM 13N 240,BETHESDA,MD 20892, USA. NR 49 TC 109 Z9 109 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0162-0886 J9 REV INFECT DIS PD MAY-JUN PY 1991 VL 13 IS 3 BP 496 EP 503 PG 8 WC Immunology; Microbiology SC Immunology; Microbiology GA FM826 UT WOS:A1991FM82600023 PM 1866556 ER PT J AU FOERSTER, A JONES, PB LEWIS, SW MURRAY, RM AF FOERSTER, A JONES, PB LEWIS, SW MURRAY, RM TI SHOULD POOR PREMORBID FUNCTIONING BE PART OF THE NEGATIVE SYNDROME SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROSCI BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 256 EP 257 DI 10.1016/0920-9964(91)90107-3 PG 2 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300019 ER PT J AU TORREY, EF BOWLER, A RAWLINGS, RR TERRAZAS, A AF TORREY, EF BOWLER, A RAWLINGS, RR TERRAZAS, A TI THE CORRELATION OF THE SEASONALITY OF SCHIZOPHRENIC BIRTHS AND STILLBIRTHS OVER A 52-YEAR TIME PERIOD SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,TWIN STUDY UNIT,WASHINGTON,DC 20032. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 269 EP 269 DI 10.1016/0920-9964(91)90131-A PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300043 ER PT J AU INGRAHAM, LJ WENDER, PH KETY, SS AF INGRAHAM, LJ WENDER, PH KETY, SS TI CHARACTERIZATION OF GENETICALLY TRANSMITTED SCHIZOPHRENIA IN DANISH ADOPTEES SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,INTRAMURAL RES PROGRAM,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 279 EP 280 DI 10.1016/0920-9964(91)90146-I PG 2 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300058 ER PT J AU POLYMEROPOULOS, MH DELISI, LE POULTER, M LOFTHOUSE, R CROW, T XIAO, H BOCCIO, AM WEBER, JL MERRIL, CR AF POLYMEROPOULOS, MH DELISI, LE POULTER, M LOFTHOUSE, R CROW, T XIAO, H BOCCIO, AM WEBER, JL MERRIL, CR TI GENETIC-LINKAGE STUDIES IN SCHIZOPHRENIA USING (CA)N REPEAT POLYMORPHISMS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,BIOCHEM GENET LAB,WASHINGTON,DC 20032. SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 283 EP 283 DI 10.1016/0920-9964(91)90154-J PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300066 ER PT J AU TORREY, EF TAYLOR, E BOWLER, A BRACHA, S QUINN, PO BIGELOW, L RICKLER, K HIGGINS, N WYATT, RJ GOTTESMAN, II AF TORREY, EF TAYLOR, E BOWLER, A BRACHA, S QUINN, PO BIGELOW, L RICKLER, K HIGGINS, N WYATT, RJ GOTTESMAN, II TI EVIDENCE OF EARLY BRAIN CHANGES IN SUBGROUP OF TWINS WITH SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,TWIN STUDY UNIT,WASHINGTON,DC 20032. RI G, I/D-8042-2011 NR 0 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 285 EP 285 DI 10.1016/0920-9964(91)90157-M PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300069 ER PT J AU WYATT, RJ AF WYATT, RJ TI THE EFFECT OF EARLY NEUROLEPTIC INTERVENTION ON THE COURSE OF SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 297 EP 297 DI 10.1016/0920-9964(91)90178-T PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300090 ER PT J AU BIGELOW, LB GOLDBERG, TE DANIEL, DG KLEINMAN, JE WEINBERGER, DR AF BIGELOW, LB GOLDBERG, TE DANIEL, DG KLEINMAN, JE WEINBERGER, DR TI AMPHETAMINE - CLINICAL-RESPONSE OF CHRONIC-SCHIZOPHRENICS TO A SINGLE ORAL DOSE SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 313 EP 313 DI 10.1016/0920-9964(91)90202-3 PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300114 ER PT J AU CLARDY, J DANIEL, DG BRESLIN, N GOLD, J KLEINMAN, J WINBERGER, DR AF CLARDY, J DANIEL, DG BRESLIN, N GOLD, J KLEINMAN, J WINBERGER, DR TI A TRIAL OF L-DOPA AND MOLINDONE IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROPSYCHIAT RES HOSP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 315 EP 316 DI 10.1016/0920-9964(91)90207-8 PG 2 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300119 ER PT J AU TAYLOR, DP SHUKLA, UA WOLFE, SA OWEN, PQ PYKE, R DESOUZA, EB AF TAYLOR, DP SHUKLA, UA WOLFE, SA OWEN, PQ PYKE, R DESOUZA, EB TI PHASE-I TRIALS OF BMY-14802, A POTENTIAL ANTIPSYCHOTIC WITH AFFINITY FOR SIGMA-BINDING SITES SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 BRISTOL MEYERS SQUIBB PHARMACEUT RES INST,METAB & PHARMACOKINET,WALLINGFORD,CT 06492. BRISTOL MEYERS SQUIBB PHARMACEUT RES INST,CNS CLIN DEV,WALLINGFORD,CT 06492. BRISTOL MEYERS SQUIBB PHARMACEUT RES INST,CNS DRUG DISCOVERY,WALLINGFORD,CT 06492. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 327 EP 327 DI 10.1016/0920-9964(91)90228-J PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300140 ER PT J AU HITRI, A CASANOVA, MF KLEINMAN, JE WEINBERGER, DR WYATT, RJ AF HITRI, A CASANOVA, MF KLEINMAN, JE WEINBERGER, DR WYATT, RJ TI AGE-DEPENDENT CHANGES IN DOPAMINE TRANSPORTER BINDING AND ITS RELEVANCE TO SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,CTR NEUROSCI,NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. ST ELIZABETH HOSP,CTR NEUROSCI,NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 346 EP 346 DI 10.1016/0920-9964(91)90259-T PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300171 ER PT J AU JASKIW, GE LARUELLE, M LIPSKA, BK ABI-DARGHAM, A WEINBERGER, DR AF JASKIW, GE LARUELLE, M LIPSKA, BK ABI-DARGHAM, A WEINBERGER, DR TI IBOTENIC ACID OR ABLATION LESIONS OF THE FRONTAL-CORTEX DO NOT ALTER THE DENSITY OR THE AFFINITY OF D1 AND D2 RECEPTORS IN THE CORPUS STRIATUM OR NUCLEUS-ACCUMBENS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP, NIMH, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 346 EP 347 DI 10.1016/0920-9964(91)90260-X PG 2 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300172 ER PT J AU KIRCH, DG SUDDATH, RL GERHARDT, GA ISSA, F FREEDMAN, R WYATT, RJ AF KIRCH, DG SUDDATH, RL GERHARDT, GA ISSA, F FREEDMAN, R WYATT, RJ TI ANALYSIS OF CEREBROSPINAL-FLUID MONOAMINES IN SCHIZOPHRENIC-PATIENTS ON AND OFF NEUROLEPTIC TREATMENT AND COMPARED WITH HEALTHY CONTROLS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROPSYCHIAT RES BRANCH,ROCKVILLE,MD 20857. NIMH,SCHIZOPHRENIA RES BRANCH,ROCKVILLE,MD 20857. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 349 EP 349 DI 10.1016/0920-9964(91)90265-S PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300177 ER PT J AU STEVENS, JR BRUTON, CJ FIRTH, CD AF STEVENS, JR BRUTON, CJ FIRTH, CD TI SCHIZOPHRENIA AND EPILEPSY - CLINICAL AND PATHOLOGICAL-STUDIES SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 373 EP 374 DI 10.1016/0920-9964(91)90304-A PG 2 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300216 ER PT J AU KIRCH, DG SUDDATH, RL FOOTE, M VIEWEG, WVR GODLESKI, L JAEGER, AC WEINBERGER, DR WYATT, RJ AF KIRCH, DG SUDDATH, RL FOOTE, M VIEWEG, WVR GODLESKI, L JAEGER, AC WEINBERGER, DR WYATT, RJ TI POLYDIPSIA-HYPONATREMIA - EVIDENCE FOR SPECIFIC CEREBRAL STRUCTURAL PATHOLOGY AND IMPLICATIONS FOR THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROPSYCHIAT BRANCH,ROCKVILLE,MD 20857. NIMH,CLIN BRAIN DISORDERS BRANCH,ROCKVILLE,MD 20857. NIMH,SCHIZOPHRENIA RES BRANCH,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 377 EP 377 DI 10.1016/0920-9964(91)90310-N PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300222 ER PT J AU WAGMAN, AMI AF WAGMAN, AMI TI SUICIDE IN SCHIZOPHRENIA - WHAT DO WE KNOW - WHERE DO WE GO SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,DIV CLIN RES,SCHIZOPHRENIA RES BRANCH,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 378 EP 379 DI 10.1016/0920-9964(91)90313-G PG 2 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300225 ER PT J AU GOLD, JM RANDOLPH, C CARPENTER, CJ GOLDBERG, TE WEINBERGER, DR AF GOLD, JM RANDOLPH, C CARPENTER, CJ GOLDBERG, TE WEINBERGER, DR TI FORMS OF MEMORY FAILURE IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 383 EP 384 DI 10.1016/0920-9964(91)90319-M PG 2 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300231 ER PT J AU GOLDBERG, TE TORREY, EF GOLD, JM RAGLAND, JD BIGELOW, LB WEINBERGER, DR AF GOLDBERG, TE TORREY, EF GOLD, JM RAGLAND, JD BIGELOW, LB WEINBERGER, DR TI MEMORY FUNCTION IN MONOZYGOTIC TWINS DISCORDANT FOR SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 384 EP 384 DI 10.1016/0920-9964(91)90320-Q PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300232 ER PT J AU GREENBERG, R GOLDBERG, TE GRIFFIN, S GOLD, JM KLEINMAN, JE PICKAR, D WEINBERGER, DR AF GREENBERG, R GOLDBERG, TE GRIFFIN, S GOLD, JM KLEINMAN, JE PICKAR, D WEINBERGER, DR TI EFFECTS OF CLOZAPINE ON COGNITION IN PATIENTS WITH SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 385 EP 385 DI 10.1016/0920-9964(91)90322-I PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300234 ER PT J AU RANDOLPH, C GOLD, JM GOLDBERG, TE WEINBERGER, DR AF RANDOLPH, C GOLD, JM GOLDBERG, TE WEINBERGER, DR TI IMPLICIT MEMORY FUNCTION IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 391 EP 391 DI 10.1016/0920-9964(91)90333-M PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300245 ER PT J AU BERMAN, KF RANDOLPH, C GOLD, J ABI-DARGHAM, A JONES, DW GOLDERG, TE CARSON, RE HERSCOVITCH, P WEINBERGER, DR AF BERMAN, KF RANDOLPH, C GOLD, J ABI-DARGHAM, A JONES, DW GOLDERG, TE CARSON, RE HERSCOVITCH, P WEINBERGER, DR TI PET STUDIES OF FRONTAL-LOBE FUNCTION DURING COGNITION SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH, NEUROSCI CTR ST ELISABETHS, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY-JUN PY 1991 VL 4 IS 3 BP 399 EP 399 DI 10.1016/0920-9964(91)90344-Q PG 1 WC Psychiatry SC Psychiatry GA FD743 UT WOS:A1991FD74300256 ER PT J AU HOOFNAGLE, JH DIBISCEGLIE, AM AF HOOFNAGLE, JH DIBISCEGLIE, AM TI SEROLOGIC DIAGNOSIS OF ACUTE AND CHRONIC VIRAL-HEPATITIS SO SEMINARS IN LIVER DISEASE LA English DT Review ID NON-B-HEPATITIS; BORNE NON-A; C VIRUS; ANTIBODY-RESPONSE; DELTA-ANTIGEN; CORE ANTIGEN; CONTROLLED TRIAL; SURFACE-ANTIGEN; LIVER BIOPSIES; INFECTION C1 NIDDKD, DIGEST DIS BRANCH, LIVER DIS SECT, BETHESDA, MD USA. NIDDKD, DIV DIGEST DIS & NUTR, BETHESDA, MD USA. NR 64 TC 80 Z9 83 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 EI 1098-8971 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 1991 VL 11 IS 2 BP 73 EP 83 DI 10.1055/s-2008-1040426 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GN065 UT WOS:A1991GN06500002 PM 1909458 ER PT J AU MILLER, RH AF MILLER, RH TI COMPARATIVE MOLECULAR-BIOLOGY OF THE HEPATITIS VIRUSES SO SEMINARS IN LIVER DISEASE LA English DT Review ID NON-B-HEPATITIS; SURFACE-ANTIGEN GENE; NON-A-HEPATITIS; DELTA-VIRUS; C VIRUS; HEPATOCELLULAR-CARCINOMA; NUCLEOTIDE-SEQUENCE; REVERSE TRANSCRIPTION; INFECTED LIVER; SELF-CLEAVAGE RP MILLER, RH (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 80 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 1991 VL 11 IS 2 BP 113 EP 120 DI 10.1055/s-2008-1040429 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GN065 UT WOS:A1991GN06500005 PM 1653457 ER PT J AU GENESCA, J ESTEBAN, JI ALTER, HJ AF GENESCA, J ESTEBAN, JI ALTER, HJ TI BLOOD-BORNE NON-A-HEPATITIS, NON-B-HEPATITIS - HEPATITIS-C SO SEMINARS IN LIVER DISEASE LA English DT Review ID POST-TRANSFUSION HEPATITIS; FACTOR-VIII CONCENTRATE; CHRONIC LIVER-DISEASE; POSTTRANSFUSION NON-A; TRANSMITTED NON-A; PRIMARY HEPATOCELLULAR-CARCINOMA; TERM FOLLOW-UP; SPORADIC NON-A; VIRUS-ANTIBODIES; INFANT TRANSMISSION C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP GENESCA, J (reprint author), UNIV VALL HEBRON,HOSP GEN,DEPT INTERNAL MED,LIVER UNIT,E-08035 BARCELONA,SPAIN. OI Genesca, Joan/0000-0002-0831-8422 NR 230 TC 75 Z9 75 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 1991 VL 11 IS 2 BP 147 EP 164 DI 10.1055/s-2008-1040432 PG 18 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GN065 UT WOS:A1991GN06500008 PM 1653459 ER PT J AU DIBISCEGLIE, AM GOODMAN, ZD AF DIBISCEGLIE, AM GOODMAN, ZD TI A 20-YEAR-OLD MAN WITH PERSISTENT AMINOTRANSFERASE ELEVATIONS SO SEMINARS IN LIVER DISEASE LA English DT Review ID HEPATITIS-B SURFACE; GROUND-GLASS HEPATOCYTES; NARCOTIC DRUG-ABUSERS; CORE ANTIGEN; DELTA-HEPATITIS; LIVER BIOPSIES; HBSAG-CARRIERS; NON-A; DISEASE; VIRUS C1 ARMED FORCES INST PATHOL,DIV HEPAT PATHOL,WASHINGTON,DC 20306. RP DIBISCEGLIE, AM (reprint author), NIDDKD,LIVER DIS SECT,BLDG 10,ROOM 4052,BETHESDA,MD 20895, USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 1991 VL 11 IS 2 BP 175 EP 181 DI 10.1055/s-2008-1040434 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GN065 UT WOS:A1991GN06500010 PM 1887257 ER PT J AU SHIN, SU DEPINHO, R ZACK, DJ RUDIKOFF, S SCHARFF, MD AF SHIN, SU DEPINHO, R ZACK, DJ RUDIKOFF, S SCHARFF, MD TI INSTABILITY OF IMMUNOGLOBULIN GENES IN S107 CELL-LINE SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID ANTIGEN-BINDING SPECIFICITY; AMINO-ACID SUBSTITUTION; HEAVY-CHAIN LOCUS; ANTIBODY REPERTOIRE; SOMATIC MUTATION; VARIABLE-REGION; ESCHERICHIA-COLI; IMMUNE-RESPONSE; MOUSE; PHOSPHORYLCHOLINE AB Somatic mutation occurs frequently in rearranged and expressed immunoglobulin variable region genes in vivo. In contrast, V region hypermutation seldom occurs in antibody-forming cells in culture. The S107 mouse myeloma cell line is one of the few cell lines that has been observed to generate V region mutations frequently and spontaneously in vitro. Detailed examination reveals that both the S107 tumor and the cell line derived from it contain and express a duplicated heavy-chain gene. In culture, only one of the two heavy-chain genes undergoes both V and C region mutation, and variants with complex phenotypes and genotypes arise as a result of mutation and segregation of these duplicated genes. C1 NCI,BETHESDA,MD 20892. RP SHIN, SU (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT CELL BIOL,1300 MORRIS PK AVE,BRONX,NY 10461, USA. OI Zack, Don/0000-0002-7966-1973 FU NCI NIH HHS [CA 39838]; NIAID NIH HHS [AI 10707]; OHS HRSA HHS [ST32CA09173] NR 47 TC 7 Z9 7 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD MAY PY 1991 VL 17 IS 3 BP 259 EP 276 DI 10.1007/BF01232821 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA FT249 UT WOS:A1991FT24900004 PM 1904631 ER PT J AU DICHEK, DA BRATTHAUER, GL BEG, ZH ANDERSON, KD NEWMAN, KD ZWIEBEL, JA HOEG, JM ANDERSON, WF AF DICHEK, DA BRATTHAUER, GL BEG, ZH ANDERSON, KD NEWMAN, KD ZWIEBEL, JA HOEG, JM ANDERSON, WF TI RETROVIRAL VECTOR-MEDIATED INVIVO EXPRESSION OF LOW-DENSITY-LIPOPROTEIN RECEPTORS IN THE WATANABE HERITABLE HYPERLIPIDEMIC RABBIT SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Article ID HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; GENE-TRANSFER; LDL RECEPTOR; WHHL-RABBIT; PLASMA-CHOLESTEROL; APOLIPOPROTEIN-E; GROWTH FACTOR; ATHEROSCLEROSIS; HEPATOCYTES; FIBROBLASTS AB We have achieved in vivo expression of recombinant low-density-lipoprotein (LDL) receptors in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for the human disease familial hypercholesterolemia. A retroviral vector was constructed containing the human LDL receptor cDNA and was used to stably transduce primary skin fibroblasts from WHHL rabbits. The integrity and function of the introduced LDL receptor was established by immunoprecipitation, by a fluorescent LDL binding assay, and by the ability of the transduced cells to suppress 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase activity in response to exogenous cholesterol. Autologous transduced fibroblasts were reimplanted into donor rabbits; in vivo LDL receptor expression and the survival of the transduced cells were analyzed by immunohistochemistry and by LDL binding assays performed on cells recovered from the implants. LDL receptor-bearing cells could be identified on tissue sections and recovered from implants for up to four weeks. Total and LDL cholesterol levels decreased significantly after implantation of the transduced cells; however, control experiments indicated that the decreases were not mediated through the recombinant LDL receptor. While in vivo stable expression of recombinant LDL receptors in Watanabe rabbits is possible, consequent changes in lipid levels must be interpreted with caution. This system of site-specific in vivo expression of recombinant LDL receptors permits further evaluation of the role of LDL receptor-gene replacement in the therapy of hypercholesterolemia. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. RP DICHEK, DA (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 50 TC 13 Z9 13 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD MAY PY 1991 VL 17 IS 3 BP 287 EP 301 DI 10.1007/BF01232823 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA FT249 UT WOS:A1991FT24900006 PM 1675491 ER PT J AU KORACH, KS CHAE, K GIBSON, M CURTIS, S AF KORACH, KS CHAE, K GIBSON, M CURTIS, S TI ESTROGEN-RECEPTOR STEREOCHEMISTRY - LIGAND-BINDING AND HORMONAL RESPONSIVENESS SO STEROIDS LA English DT Article; Proceedings Paper CT 25TH ANNIVERSARY SYMP IN HONOR OF THE PHD PROGRAM IN ENDOCRINOLOGY OF THE MEDICAL COLLEGE OF GEORGIA CY JUN 19, 1990 CL MED COLL GEORGIA, AUGUSTA, GA SP MED COLL GEORGIA HO MED COLL GEORGIA DE STEROIDS; HORMONE RESPONSE; STILBENE; ESTROGEN RECEPTOR; UTERINE; STRUCTURE-ACTIVITY; DNA SYNTHESIS; ORNITHINE DECARBOXYLASE; DIETHYLSTILBESTROL; ENANTIOMERS AB Estrogen stimulation of the uterus produces a spectrum of biochemical responses that are customarily linked together. This report is an overview of a series of studies by our laboratory investigating the role of different ligand structures in eliciting hormonal responses. Diethylstilbestrol (DES) and certain structural analogs, indenestrol A (IA), indenestrol B (IB), and pseudo-DES, were used as probes to segregate various genomic responses previously considered interrelated, most notably the events of specific protein synthesis and DNA synthesis. These compounds have weak uterotrophic activity; however, they interact with high affinity specifically with mouse uterine estrogen receptors (ERs). All of them produce stoichiometrically similar amounts of ER complex in the nucleus. Indenestrol A and IB possess a single chiral carbon atom and exist as a mixture of enantiomers (ENTs). Competitive binding assays of pure ENTs and cytosolic ERs demonstrated a stereochemical chiral preference for the IA isomer but not IB. This preference was also evident from nuclear ER occupancy experiments. Biologic activity of the IA ENTs also demonstrated differences as seen by receptor binding. Ornithine decarboxylase (ODC) activity was stimulated 600% by DES and partially by IA (rac). All of the ODC activity produced by IA (rac) was due to the IA(C3)-S ENT. Uterine DNA synthesis was measured after treatment with the IA compounds. Indenestrol A (rac) increased DNA synthesis to 40% of the level seen with DES. The weak ENTs showed no activity and the active ENTs were weaker than the IA racemic. These compounds should be useful probes for studying the individual responses involved in estrogen-induced uterine growth. The data also indicate that induction of some biologic responses, such as ODC, progesterone receptor, and DNA synthesis are not coupled. Therefore, stimulation of a certain uterine response may depend on the structure of the particular ligand receptor complex formed, and its interaction may be regulated by specificity at the genomic acceptor site. RP KORACH, KS (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 0 TC 44 Z9 44 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0039-128X J9 STEROIDS JI Steroids PD MAY PY 1991 VL 56 IS 5 BP 263 EP 270 DI 10.1016/0039-128X(91)90045-W PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA FJ984 UT WOS:A1991FJ98400009 PM 1877066 ER PT J AU DUNNICK, JK EUSTIS, SL AF DUNNICK, JK EUSTIS, SL TI DECREASES IN SPONTANEOUS TUMORS IN RATS AND MICE AFTER TREATMENT WITH AMPHETAMINE SO TOXICOLOGY LA English DT Article DE AMPHETAMINE; CARCINOGENESIS STUDIES; F344/N RAT; B6C3F1 MOUSE ID BODY-WEIGHT; LONG-TERM; PROLIFERATION; RESTRICTION; DRUG AB Toxicology and carcinogenesis studies of dl-amphetamine sulfate, a drug used in the treatment of weight control, narcolepsy, and behavioral syndromes in children, were performed in F344/N rats and B6C3F1 mice. In these studies, amphetamine was administered for 2 years at doses of 0, 20, or 100 ppm in the feed to groups of 50 animals/dose/sex/species. The average amount of amphetamine consumed per day was estimated to be 1 or 5 mg/kg for low or high dose rats, 4 or 30 mg/kg for low or high dose male mice, and 3 or 19 mg/kg for low or high dose female mice. Survival was similar in dosed and control groups. The most notable effect of long-term treatment with this drug was the reduction of body weight in comparison to controls, and reduction in spontaneous tumors including pheochromocytomas of the adrenal gland in male rats, fibroadenomas of the mammary gland in female rats, adenomas of the anterior pituitary gland in male and female rats and female mice, endometrial stromal polyps of the uterus of female rats, adenomas or carcinomas of the liver in male and female mice, adenomas of the Harderian gland in male and female mice, and adenomas or carcinomas of the lung in male and female mice. Decreases in spontaneous tumors have previously been seen in 2-year rodent studies in groups of animals that have a reduced body weight in comparison to controls, but the spectrum of reduction in spontaneous neoplasms after treatment with amphetamine is broader than has previously been observed. RP DUNNICK, JK (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAY PY 1991 VL 67 IS 3 BP 325 EP 332 DI 10.1016/0300-483X(91)90031-U PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA FR264 UT WOS:A1991FR26400006 PM 2048132 ER PT J AU WAALKES, MP KOVATCH, R REHM, S AF WAALKES, MP KOVATCH, R REHM, S TI EFFECT OF CHRONIC DIETARY ZINC-DEFICIENCY ON CADMIUM TOXICITY AND CARCINOGENESIS IN THE MALE WISTAR [HSD-(WI)BR] RAT SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID INDUCED ESOPHAGEAL CANCER; DOSE-RESPONSE ANALYSIS; SPRAGUE-DAWLEY RATS; NICKEL SUBSULFIDE; CRL-(WI)BR RATS; TUMOR-INDUCTION; INJECTION SITE; METALLOTHIONEIN; PROSTATE; HEPATOCARCINOGENESIS C1 NCI,FREDERICK CANC RES FACIL,COMPARAT CARCINOGENESIS LAB,PATHOGENESIS SECT,FREDERICK,MD 21701. PATHOL ASSOCIATES INC,FREDERICK,MD. RP WAALKES, MP (reprint author), NCI,FREDERICK CANC RES FACIL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74102] NR 43 TC 40 Z9 40 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1991 VL 108 IS 3 BP 448 EP 456 DI 10.1016/0041-008X(91)90091-R PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA FJ647 UT WOS:A1991FJ64700008 PM 2020969 ER PT J AU ADEYEMO, OM SHAPIRA, S TOMBACCINI, D POLLARD, HB FEUERSTEIN, G SIREN, AL AF ADEYEMO, OM SHAPIRA, S TOMBACCINI, D POLLARD, HB FEUERSTEIN, G SIREN, AL TI A GOLDFISH MODEL FOR EVALUATION OF THE NEUROTOXICITY OF OMEGA-CONOTOXIN GVI-A AND SCREENING OF MONOCLONAL-ANTIBODIES SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID SENSITIVE CALCIUM-CHANNEL; PEPTIDE; RELEASE; SYSTEM; TECTUM; BRAIN; FISH; RAT C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. SMITHKLINE BEECHAM,DEPT PHARMACOL,KING OF PRUSSIA,PA 19406. RP ADEYEMO, OM (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,BETHESDA,MD 20814, USA. NR 28 TC 8 Z9 8 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 MAY PY 1991 VL 108 IS 3 BP 489 EP 496 DI 10.1016/0041-008X(91)90095-V PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA FJ647 UT WOS:A1991FJ64700012 PM 1850561 ER PT J AU FRICKE, W ALLING, D KIMBALL, J GRIFFITH, P KLEIN, H AF FRICKE, W ALLING, D KIMBALL, J GRIFFITH, P KLEIN, H TI LACK OF EFFICACY OF TRANEXAMIC ACID IN THROMBOCYTOPENIC BLEEDING SO TRANSFUSION LA English DT Article ID EPSILON-AMINOCAPROIC ACID; DOUBLE-BLIND; ANTIFIBRINOLYTIC TREATMENT; SUBARACHNOID HEMORRHAGE; THERAPY AB A controlled, randomized, double-blind study was performed to assess the effect of the oral antifibrinolytic agent tranexamic acid in patients with amegakaryocytic thrombocytopenia as regards their need for platelet transfusions and the number of bleeding episodes experienced. Each patient served as his or her own control and received sequential, randomized courses of either tranexamic acid or an identical placebo. The need for platelet transfusions due to bleeding and the total number of bleeding episodes were compared for tranexamic acid and placebo courses. Patients received platelet transfusions at the discretion of their personal physician and kept detailed records of bleeding episodes. Of three patients who completed the full study, none had a reduction in the need for platelet transfusions. Moreover, in the eight patients who participated in the study, there was no reduction in number of bleeding episodes during tranexamic acid treatment as compared to the number with placebo. our data indicate that the prophylactic administration of tranexamic acid does not decrease dependence on platelet transfusions or decrease bleeding episodes in patients with bleeding due to amegakaryocytic thrombocytopenia. C1 NIAID,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. NIH,CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 22 TC 20 Z9 20 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 MAY PY 1991 VL 31 IS 4 BP 345 EP 348 DI 10.1046/j.1537-2995.1991.31491213301.x PG 4 WC Hematology SC Hematology GA FK316 UT WOS:A1991FK31600017 PM 1823527 ER PT J AU CLASSEN, JB SHEVACH, EM AF CLASSEN, JB SHEVACH, EM TI EVIDENCE THAT CYCLOSPORINE TREATMENT DURING PREGNANCY PREDISPOSES OFFSPRING TO DEVELOP AUTOANTIBODIES SO TRANSPLANTATION LA English DT Article ID VERSUS-HOST DISEASE; ATHYMIC NUDE-MICE; AUTOIMMUNE GASTRITIS; MONOCLONAL-ANTIBODY; DIFFERENTIATION; THYMOCYTES; ANTIGENS; ANEMIA AB Cyclosporine was administered (11 mg/kg/day) to pregnant mice to study the effects of passively transferred CsA on the developing immune system. Placental transfer of CsA was shown by the detection of fetal-tissue levels ranging from 400 to 1500 ng CsA/g tissue. Treatment clearly altered the developing immune system. Thymuses from the day-18 embryos exposed to CsA were partially depleted of CD4+CD8- single positive cells. Eleven of 50 offspring born to CsA-treated mothers developed significant levels of IgG autoantibodies to gastric antigens. In addition, two animals that received CsA in utero developed an extensive mononuclear cell infiltrate in the gastric mucosa resembling autoimmune gastritis. These results raise the possibility that the administration of CsA during pregnancy may result in potential long-term effects on the developing immune system. Offspring of such pregnancies may suffer an increased incidence or severity of autoimmune diseases. RP CLASSEN, JB (reprint author), NIAID,IMMUNOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 11N315,BETHESDA,MD 20892, USA. NR 17 TC 25 Z9 25 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 MAY PY 1991 VL 51 IS 5 BP 1052 EP 1057 DI 10.1097/00007890-199105000-00024 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA FM344 UT WOS:A1991FM34400024 PM 1903221 ER PT J AU WISTOW, GJ PISANO, MM CHEPELINSKY, AB AF WISTOW, GJ PISANO, MM CHEPELINSKY, AB TI TANDEM SEQUENCE REPEATS IN TRANSMEMBRANE CHANNEL PROTEINS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID MAJOR INTRINSIC PROTEIN; LENS FIBER MEMBRANE; ESCHERICHIA-COLI; SOYBEAN NODULIN-26; RESOLUTION; PORIN AB The flow of ions and small molecules out of and between cells is mediated by various classes of transmembrane proteins. One group of putative channel proteins, including the abundant lens protein MlP, is widely distributed from prokaryotes to vertebrates. This article suggests that these proteins contain a structural twofold repeat and may have arisen by gene duplication. Such a model has implications for the tertiary structures of these important proteins. RP WISTOW, GJ (reprint author), NEI,MOLEC & DEV BIOL,BETHESDA,MD 20892, USA. NR 10 TC 95 Z9 98 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1991 VL 16 IS 5 BP 170 EP 171 DI 10.1016/0968-0004(91)90065-4 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FM156 UT WOS:A1991FM15600003 PM 1715617 ER PT J AU ANTAL, M BUZSAKI, G CZEH, G GAAL, G GULYAS, B HORVATH, Z JAKAB, R KABAI, P KISS, J KOCSIS, B KOMOLY, S KOVACH, J LENDVAY, J LERANTH, C MEZEY, E MOLNAR, Z SEREGI, A SOLTESZ, I SOMOGYI, P TOTH, T URBAN, L VADASZ, C AF ANTAL, M BUZSAKI, G CZEH, G GAAL, G GULYAS, B HORVATH, Z JAKAB, R KABAI, P KISS, J KOCSIS, B KOMOLY, S KOVACH, J LENDVAY, J LERANTH, C MEZEY, E MOLNAR, Z SEREGI, A SOLTESZ, I SOMOGYI, P TOTH, T URBAN, L VADASZ, C TI THE PATH FORWARD IN HUNGARIAN NEUROSCIENCE SO TRENDS IN NEUROSCIENCES LA English DT Letter C1 RUTGERS STATE UNIV,CTR MOLEC BEHAV NEUROSCI,NEWARK,NJ 07102. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. UNIV PENN,DEPT PHYSIOL,PHILADELPHIA,PA 19104. KAROLINSKA INST,DEPT CLIN NEUROPHYSIOL,S-10401 STOCKHOLM 60,SWEDEN. KAROLINSKA HOSP,S-10401 STOCKHOLM 60,SWEDEN. YALE UNIV,SCH MED,DEPT OBSTET GYNAECOL,NEW HAVEN,CT 06510. MENNINGER CLIN,DEPT RES,TOPEKA,KS. UNIV GENEVA,SCH MED,DEPT MORH,CH-1211 GENEVA 4,SWITZERLAND. FLORIDA ATLANTIC UNIV,CENT COMPL SYST,BOCA RATON,FL 33431. NINCDS,LENP,BETHESDA,MD 20892. NIMH,LCB,BETHESDA,MD 20892. UNIV OXFORD,DEPT PHYSIOL,OXFORD,ENGLAND. UNIV FREIBURG,DEPT PHARMACOL,W-7800 FREIBURG,GERMANY. UNIV LONDON,INST OPHTHALMOL,DEPT VISUAL SCI,LONDON,ENGLAND. MRC,DEPT PHARMACOL,ANAT NEUROPHARM UNIT,OXFORD,ENGLAND. UNIV OXFORD,DEPT EXPTL PSYCHOL,OXFORD,ENGLAND. SANDOZ INST MED RES,LONDON,ENGLAND. NATATHAN S KLINE INST,NEUROBEHAV GENET LAB,ORANGEBURG,SC. RP ANTAL, M (reprint author), NINCDS,NEUROL CONT LAB,BETHESDA,MD 20892, USA. RI Kocsis, Bernat/A-8377-2008 NR 4 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 1991 VL 14 IS 5 BP 185 EP 187 DI 10.1016/0166-2236(91)90102-Z PG 3 WC Neurosciences SC Neurosciences & Neurology GA FJ499 UT WOS:A1991FJ49900007 PM 1713719 ER PT J AU VESIKARI, T VARIS, T GREEN, K FLORES, J KAPIKIAN, AZ AF VESIKARI, T VARIS, T GREEN, K FLORES, J KAPIKIAN, AZ TI IMMUNOGENICITY AND SAFETY OF RHESUS HUMAN ROTAVIRUS REASSORTANT VACCINES WITH SEROTYPE-1 OR SEROTYPE-2 VP7 SPECIFICITY SO VACCINE LA English DT Article DE DIARRHEA; ROTAVIRUS; VACCINE; GENETIC REASSORTANTS ID YOUNG-CHILDREN; INFANTS; RESISTANCE; MMU-18006; DIARRHEA; TRIAL AB Rhesus-human rotavirus reassortants incorporating the gene expressing the VP7 surface protein of human rotavirus serotypes 1 or 2, and the remaining ten genes from rhesus rotavirus (RRV) were evaluated as candidate oral vaccines in 2-4-month-old infants. A single dose of the serotype 1 reassortant vaccine which had a titre of 10(4) plaque-forming units (p.f.u.) induced by a fourfold or greater antibody response in 81% of the recipients by a combination of ELISA and neutralization assays; 51% of the vaccines developed a neutralizing antibody response to the vaccine strain. A single dose of the serotype 2 vaccine (10(4) p.f.u.) induced a seroresponse in all vaccines by the combination of assays whereas 67% developed neutralizing antibodies to the vaccine strain. A combination of these two vaccines (0.5 x 10(4) p.f.u. of each) induced an overall seroresponse in 95% of the recipients but only 48% and 24% response in neutralizing antibodies to serotypes 1 and 2, respectively. A trivalent combination which included the two reassortants and RRV (0.33 x 10(4) p.f.u. of each strain) induced an overall response in 82% of the vaccines, but only 30%, 20% and 65% developed a neutralizing antibody response to serotype 1, serotype 2, and RRV, respectively. Febrile reactions on days 2-5 after vaccination were seen in 23-45% of the infants receiving the various vaccines and combinations and in 5% of the placebo group. It is concluded that rhesus-human reassortant rotaviruses may be combined with each other and with RRV as a polyvalent vaccine, but the VP7-specific neutralizing antibody responses are likely to be lower after combined vaccination than following vaccination with a single reassortant rotavirus. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP VESIKARI, T (reprint author), UNIV TAMPERE,DEPT CLIN SCI,SF-33520 TAMPERE,FINLAND. NR 24 TC 24 Z9 24 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD MAY PY 1991 VL 9 IS 5 BP 334 EP 339 DI 10.1016/0264-410X(91)90060-J PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA FH523 UT WOS:A1991FH52300010 PM 1651610 ER PT J AU ZIBERT, A SELINKA, HC ELROYSTEIN, O MOSS, B WIMMER, E AF ZIBERT, A SELINKA, HC ELROYSTEIN, O MOSS, B WIMMER, E TI VACCINIA VIRUS-MEDIATED EXPRESSION AND IDENTIFICATION OF THE HUMAN POLIOVIRUS RECEPTOR SO VIROLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; IMMUNOGLOBULIN SUPERFAMILY; HELA-CELLS; MONOCLONAL-ANTIBODIES; RHINOVIRUS RECEPTOR; ATTACHMENT; PROTEIN; ICAM-1; RECOGNITION; CLONING C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP ZIBERT, A (reprint author), SUNY STONY BROOK,DEPT MICROBIOL,STONY BROOK,NY 11794, USA. OI Elroy-Stein, Orna/0000-0002-3716-1540 FU NCI NIH HHS [CA-28146]; NIAID NIH HHS [AI-15122] NR 45 TC 15 Z9 15 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 MAY PY 1991 VL 182 IS 1 BP 250 EP 259 DI 10.1016/0042-6822(91)90668-2 PG 10 WC Virology SC Virology GA FG180 UT WOS:A1991FG18000028 PM 1850905 ER PT J AU LIU, JM FUJII, H GREEN, SW KOMATSU, N YOUNG, NS SHIMADA, T AF LIU, JM FUJII, H GREEN, SW KOMATSU, N YOUNG, NS SHIMADA, T TI INDISCRIMINATE ACTIVITY FROM THE B19 PARVOVIRUS P6 PROMOTER IN NONPERMISSIVE CELLS SO VIROLOGY LA English DT Note ID FIREFLY LUCIFERASE; MAMMALIAN-CELLS; GENE; DNA; EXPRESSION; MARROW; INFECTION; REGION; REPEAT; VIRUS C1 NEW YORK BLOOD CTR,HEMATOPOIET GROWTH FACTORS LAB,310 E 67TH ST,NEW YORK,NY 10021. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 23 TC 54 Z9 54 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 MAY PY 1991 VL 182 IS 1 BP 361 EP 364 DI 10.1016/0042-6822(91)90682-2 PG 4 WC Virology SC Virology GA FG180 UT WOS:A1991FG18000042 PM 2024472 ER PT J AU FOMSGAARD, A HIRSCH, VM ALLAN, JS JOHNSON, PR AF FOMSGAARD, A HIRSCH, VM ALLAN, JS JOHNSON, PR TI A HIGHLY DIVERGENT PROVIRAL DNA CLONE OF SIV FROM A DISTINCT SPECIES OF AFRICAN-GREEN MONKEY SO VIROLOGY LA English DT Note ID SIMIAN IMMUNODEFICIENCY VIRUS; GLYCOPROTEIN; INFECTION; REGION C1 NIAID,INFECT DIS LAB,TWINBROOK 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852. GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,RETROVIRAL PATHOGENESIS SECT,WASHINGTON,DC 20007. SW FDN BIOMED RES,DEPT VIROL & IMMUNOL,SAN ANTONIO,TX 78284. RI Johnson, Philip/A-6892-2009 FU NIAID NIH HHS [N01-AI-72623] NR 20 TC 61 Z9 69 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY PY 1991 VL 182 IS 1 BP 397 EP 402 DI 10.1016/0042-6822(91)90689-9 PG 6 WC Virology SC Virology GA FG180 UT WOS:A1991FG18000049 PM 2024476 ER PT J AU QIAN, Y GREEN, KY AF QIAN, Y GREEN, KY TI HUMAN ROTAVIRUS STRAIN 69M HAS A UNIQUE VP4 AS DETERMINED BY AMINO-ACID-SEQUENCE ANALYSIS SO VIROLOGY LA English DT Note ID COMPLETE NUCLEOTIDE-SEQUENCE; MOLECULAR MECHANISMS; RHESUS ROTAVIRUS; GENE; NEUTRALIZATION; IDENTIFICATION; SPECIFICITIES; INFECTIVITY; SA11; ENHANCEMENT C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 30 TC 68 Z9 74 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY PY 1991 VL 182 IS 1 BP 407 EP 412 DI 10.1016/0042-6822(91)90691-4 PG 6 WC Virology SC Virology GA FG180 UT WOS:A1991FG18000051 PM 1850912 ER PT J AU DE, BK LAIRMORE, MD GRIFFIS, K WILLIAMS, LJ VILLINGER, F QUINN, TC BROWN, C NZILAMBI SUGIMOTO, M ARAKI, S FOLKS, TM AF DE, BK LAIRMORE, MD GRIFFIS, K WILLIAMS, LJ VILLINGER, F QUINN, TC BROWN, C NZILAMBI SUGIMOTO, M ARAKI, S FOLKS, TM TI COMPARATIVE-ANALYSIS OF NUCLEOTIDE-SEQUENCES OF THE PARTIAL ENVELOPE GENE (5' DOMAIN) AMONG HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) ISOLATES SO VIROLOGY LA English DT Note ID CELL LEUKEMIA-VIRUS; RETROVIRUS HTLV; UNITED-STATES; ANTIBODIES; PROVIRUS; BLOOD; HIV; PARTICLES; INFECTION; LYMPHOMA C1 OHIO STATE UNIV,DEPT VET PATHOBIOL,COLUMBUS,OH 43210. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. EMORY UNIV,DEPT PATHOL & LAB MED,ATLANTA,GA 30322. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. KUMAMOTO UNIV,DEPT INTERNAL MED 1,KUMAMOTO 860,JAPAN. PROJECT SIDA,KINCHOSA,ZAIRE. RP DE, BK (reprint author), CTR DIS CONTROL,CTR INFECT DIS,DVRD,RETROVIRUS DIS BRANCH,MAIL STOP G19,ATLANTA,GA 30333, USA. NR 36 TC 43 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY PY 1991 VL 182 IS 1 BP 413 EP 419 DI 10.1016/0042-6822(91)90692-5 PG 7 WC Virology SC Virology GA FG180 UT WOS:A1991FG18000052 PM 2024477 ER PT J AU ELOVAARA, E ENGSTROM, K NAKAJIMA, T PARK, SS GELBOIN, HV VAINIO, H AF ELOVAARA, E ENGSTROM, K NAKAJIMA, T PARK, SS GELBOIN, HV VAINIO, H TI METABOLISM OF INHALED STYRENE IN ACETONE-PRETREATED, PHENOBARBITAL-PRETREATED AND 3-METHYLCHOLANTHRENE-PRETREATED RATS - STIMULATION AND STEREOCHEMICAL EFFECTS BY INDUCTION OF CYTOCHROME-P450IIE1, CYTOCHROME-P450IIB AND CYTOCHROME-P450IA SO XENOBIOTICA LA English DT Article ID MONOCLONAL-ANTIBODIES; INHALATION PHARMACOKINETICS; LIVER CYTOCHROME-P-450; VOLATILE HYDROCARBONS; URINARY-EXCRETION; ENZYME-INDUCTION; EXPOSED PERSONS; MANDELIC-ACID; ETHANOL; OXIDATION AB 1. The effect of various cytochrome P-450 inducers, namely acetone, phenobarbital (PB) and 3-methylcholanthrene (MC), on the pharmacokinetics of styrene metabolism was studied. 2. Styrene metabolism in vivo was studied measuring phenylglyoxylic acid (PGA), the enantiomers of mandelic acid (MA), and total thioethers excreted in the urine during a 24 h period of airborne exposure to styrene at 500 cm3/m3 (2100 mg/m3). In acetone-pretreated rats, PGA and MA and thioether formation were elevated 30-50%. The R/S ratio of MA enantiomers was about two in all styrene-exposed groups except PB-pretreated rats, which showed a ratio of four. 3. Styrene metabolism in liver microsomes measured in vitro was increased by styrene 140%, acetone plus styrene by 190%, methylcholanthrene plus styrene by 180% and phenobarbital plus styrene by 250%. 4. N-Nitrosodimethylamine demethylation (NDMAD) and 7-pentoxyresorufin dealkylation (PROD) in liver microsomes were enhanced 100-150% by styrene inhalation. The metabolism of 7-ethoxyresorufin was not significantly enhanced. 5. Monoclonal antibodies to P-450 IA1, IA2, IIB1 and IIE1 were utilized to identify cytochrome P-450s by Western blot analysis. These studies showed clearly that styrene inhalation induced principally cytochrome P450IE1, whereas styrene given by gavage at a high narcotic dosage induced both P450IIE1 (NDMAD, 60%) and P450IIB (PROD, 3000%). 6. Our conclusions are that styrene metabolism in vivo is both autoinduced and induced by other foreign compounds, that cytochrome P450IIE1 induction has a major impact on styrene metabolism and that P450IIB1 induction yields an altered MA metabolite enantiomer ratio. C1 SHINSHU UNIV,SCH MED,DEPT HYG,MATSUMOTO,NAGANO 390,JAPAN. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP ELOVAARA, E (reprint author), INST OCCUPAT HLTH,TOPELIUKSENKATU 41 AA,SF-00250 HELSINKI,FINLAND. NR 48 TC 31 Z9 32 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAY PY 1991 VL 21 IS 5 BP 651 EP 661 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA FQ382 UT WOS:A1991FQ38200011 PM 1949898 ER PT J AU ADAMO, ML BENHUR, H LEROITH, D ROBERTS, CT AF ADAMO, ML BENHUR, H LEROITH, D ROBERTS, CT TI TRANSCRIPTION INITIATION IN THE 2 LEADER EXONS OF THE RAT IGF-I GENE OCCURS FROM DISPERSE VERSUS LOCALIZED SITES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GROWTH FACTOR-I; MESSENGER RIBONUCLEIC-ACID; 5'-UNTRANSLATED REGIONS; EXPRESSION; SEQUENCE RP ADAMO, ML (reprint author), NIDDKD,DIABET BRANCH,BETHESDA,MD 20892, USA. NR 13 TC 89 Z9 89 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 30 PY 1991 VL 176 IS 2 BP 887 EP 893 DI 10.1016/S0006-291X(05)80269-4 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FK023 UT WOS:A1991FK02300051 PM 2025299 ER PT J AU KAY, LE FORMANKAY, JD MCCUBBIN, WD KAY, CM AF KAY, LE FORMANKAY, JD MCCUBBIN, WD KAY, CM TI SOLUTION STRUCTURE OF A POLYPEPTIDE DIMER COMPRISING THE 4TH CA2+-BINDING SITE OF TROPONIN-C BY NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY SO BIOCHEMISTRY LA English DT Article ID INTERPROTON DISTANCE RESTRAINTS; PROTEIN-STRUCTURE DETERMINATION; CALCIUM-BINDING PROTEINS; CHICKEN SKELETAL-MUSCLE; 3-DIMENSIONAL STRUCTURES; MOLECULAR-DYNAMICS; PROTEOLYTIC FRAGMENTS; SOLUTION CONFORMATION; TRYPTIC FRAGMENTS; REFINED STRUCTURE AB The structure of a 39 amino acid proteolytic fragment of rabbit skeletal troponin C containing the fourth Ca2+-binding site has been determined by an approach involving nuclear magnetic resonance (NMR) spectroscopy combined with hybrid distance geometry-dynamics simulated annealing calculations. Hydrodynamic and NMR evidence establishes unambiguously that the fragment forms a stable dimer in solution in the presence of excess CA2+. The calculation of the dimeric structure is based on a total of 1056 experimental restraints comprising 422 interproton distances, 35-phi, 28-psi, and 28-chi-1 torsiion angle restraints within each subunit, 30 intermonomer distance restraints, and 6 Ca2+ restraints per subunit. A total of 48 final structures were calculated having an rms deviation about the mean atomic backbone coordinate positions of 1.0 angstrom for residues Asp128-Glu156. The solution structure consists of a dimer of helix-loop-helix motifs related by a 2-fold axis of symmetry. The overall architecture of the dimer is very similar to the C-terminal domain in the crystal structure of chicken skeletal troponin C. C1 UNIV ALBERTA,DEPT BIOCHEM,MRC,PROT STRUCT & FUNCT GRP,EDMONTON T6G 2H7,ALBERTA,CANADA. RP KAY, LE (reprint author), NIDDKK,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. NR 64 TC 61 Z9 62 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 APR 30 PY 1991 VL 30 IS 17 BP 4323 EP 4333 DI 10.1021/bi00231a031 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK234 UT WOS:A1991FK23400031 PM 2021624 ER PT J AU GULYA, K GRANT, KA VALVERIUS, P HOFFMAN, PL TABAKOFF, B AF GULYA, K GRANT, KA VALVERIUS, P HOFFMAN, PL TABAKOFF, B TI BRAIN REGIONAL SPECIFICITY AND TIME-COURSE OF CHANGES IN THE NMDA RECEPTOR IONOPHORE COMPLEX DURING ETHANOL WITHDRAWAL SO BRAIN RESEARCH LA English DT Article DE ETHANOL PHYSICAL DEPENDENCE; NMDA RECEPTOR; MK-801 BINDING; HIPPOCAMPUS; ETHANOL WITHDRAWAL SEIZURE; MK-801 AUTORADIOGRAPHY ID ALCOHOL WITHDRAWAL; BINDING-SITES; RAT-BRAIN; MICE; INHIBITION; SEIZURES; MK-801 AB Previous work, using membrane receptor binding techniques, demonstrated an increase in hippocampal MK-801 binding sites in mice after chronic ethanol ingestion. The current studies, using quantitative autoradiography, demonstrate that chronic ethanol ingestion also produces increases in MK-801 binding in cerebral cortex, striatum and thalamus, as well as in hippocampus. The persistence of changes in MK-801 binding paralleled the time-course for ethanol withdrawal seizure susceptibility. These results support the hypothesis that an increase in the number of NMDA receptor/channel complexes in hippocampus, and possibly other brain regions, plays a role in the generation or expression of ethanol withdrawal seizures. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,PHYSIOL & PHARMACOL STUDIES LAB,ROCKVILLE,MD 20852. NR 30 TC 253 Z9 255 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 26 PY 1991 VL 547 IS 1 BP 129 EP 134 PG 6 WC Neurosciences SC Neurosciences & Neurology GA FK666 UT WOS:A1991FK66600017 PM 1830510 ER PT J AU KAPLAN, DR HEMPSTEAD, BL MARTINZANCA, D CHAO, MV PARADA, LF AF KAPLAN, DR HEMPSTEAD, BL MARTINZANCA, D CHAO, MV PARADA, LF TI THE TRK PROTOONCOGENE PRODUCT - A SIGNAL TRANSDUCING RECEPTOR FOR NERVE GROWTH-FACTOR SO SCIENCE LA English DT Article ID SYMPATHETIC-GANGLIA MEMBRANES; SIMIAN SARCOMA-VIRUS; TYROSINE PHOSPHORYLATION; PHEOCHROMOCYTOMA CELLS; GENE-TRANSFER; CHICK-EMBRYO; PC12 CELLS; EXPRESSION; AFFINITY; SYSTEM AB The trk proto-oncogene encodes a 140-kilodalton, membrane-spanning protein tyrosine kinase (p140prototrk) that is expressed only in neural tissues. Nerve growth factor (NGF) stimulates phosphorylation of p140prototrk in neural cell lines and in embryonic dorsal root ganglia. Affinity cross-linking and equilibrium binding experiments with I-125-labeled NGF indicate that p140prototrk binds NGF specifically in cultured cells with a dissociation constant of 10(-9) molar. The identification of p140prototrk as an NGF receptor indicates that this protein participates in the primary signal transduction mechanism of NGF. C1 NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LAB,FREDERICK,MD 21701. CORNELL UNIV,MED CTR,COLL MED,DEPT CELL BIOL & ANAT,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,COLL MED,DEPT MED,DIV HEMATOL ONCOL,NEW YORK,NY 10021. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101] NR 56 TC 1181 Z9 1187 U1 2 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 26 PY 1991 VL 252 IS 5005 BP 554 EP 558 DI 10.1126/science.1850549 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FJ127 UT WOS:A1991FJ12700043 PM 1850549 ER PT J AU NEBREDA, AR MARTINZANCA, D KAPLAN, DR PARADA, LF SANTOS, E AF NEBREDA, AR MARTINZANCA, D KAPLAN, DR PARADA, LF SANTOS, E TI INDUCTION BY NGF OF MEIOTIC MATURATION OF XENOPUS OOCYTES EXPRESSING THE TRK PROTOONCOGENE PRODUCT SO SCIENCE LA English DT Article ID BIOCHEMICAL-CHARACTERIZATION; RECEPTOR; PROTEINS; ACTIVATION; SEQUENCES AB The effect of nerve growth factor (NGF) was assessed in Xenopus oocytes expressing the human trk proto-oncogene product, p140prototrk. Oocytes injected with trk messenger RNA expressed polypeptides recognized by antibodies to the trk gene product. Exposure of these oocytes to nanomolar amounts of NGF resulted in specific surface binding of I-125-labeled NGF, tyrosine phosphorylation of p140prototrk, and meiotic maturation, as determined by germinal vesicle breakdown and maturation promoting factor (p34cdc2) kinase activation. Thus the trk proto-oncogene product can act as a receptor for NGF in a functionally productive manner. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LAB,FREDERICK,MD 21701. RI Parada, luis/B-9400-2014 NR 27 TC 110 Z9 111 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 26 PY 1991 VL 252 IS 5005 BP 558 EP 560 DI 10.1126/science.1850550 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FJ127 UT WOS:A1991FJ12700044 PM 1850550 ER PT J AU GUSOVSKY, F SOERGEL, DG DALY, JW AF GUSOVSKY, F SOERGEL, DG DALY, JW TI EFFECTS OF MASTOPARAN AND RELATED PEPTIDES ON PHOSPHOINOSITIDE BREAKDOWN IN HL-60 CELLS AND CELL-FREE PREPARATIONS SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE MASTOPARAN; PHOSPHOLIPASE-C; G-PROTEINS; AMPHIPHILIC PEPTIDES ID WASP VENOM; AMPHIPHILIC PEPTIDES; CHEMOTACTIC PEPTIDE; INOSITOL PHOSPHATES; STREPTOLYSIN-O; HL60 CELLS; MAST-CELLS; TOXIN; HYDROLYSIS; MEMBRANE AB In differentiated HL-60 cells the amphiphilic peptide mastoparan induces a dose-dependent stimulation of phosphoinositide breakdown with an EC50 value of 9-mu-M. Such stimulation can be markedly reduced by pretreatment of the cells with pertussis toxin (100 ng/ml, 2 h). In membranes obtained from differentiated HL-60 cells, guanine nucleotides stimulate the formation of IP2 and IP3. Calcium ions also induce phosphoinositide breakdown in this preparation independent of the presence of guanine nucleotides. In HL-60 cell membranes, mastoparan inhibited GTP-gamma-S-stimulation of phosphoinositide breakdown with an IC50 value of 3-mu-M. Such inhibitory activity of mastoparan also was present in membranes from cells pretreated with pertussis toxin. Calcium-induced stimulation of phosphoinositide breakdown was not significantly inhibited by mastoparan. The analogs mastoparan-X and polistes mastoparan had similar inhibitory activity, whereas the analog des-Ile1-Asn2-mastoparan was inactive. In permeabilized HL-60 cells mastoparan also inhibited phosphoinositide breakdown. Another amphiphilic peptide, melittin, was inactive in HL-60 intact cells, but similar to mastoparan, inhibited guanine nucleotide-induced phosphoinositide breakdown in HL-60 cell membranes and permeabilized cells. Thus, mastoparan peptides can stimulate phosphoinositide breakdown in intact HL-60 cells, probably through the interaction with a guanine nucleotide binding protein. In permeabilized cells and in cell membranes, mastoparan induces inhibition of guanine nucleotide-mediated phosphoinositide breakdown presumably through an interaction with an intracellular site. The inhibitory action of mastoparan and melittin is probably related to the amphiphilic character of these peptides. RP GUSOVSKY, F (reprint author), NIDDK,BIOORGAN CHEM LAB,BLDG 8,ROOM 1A-15,BETHESDA,MD 20892, USA. NR 22 TC 21 Z9 22 U1 0 U2 1 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 APR 25 PY 1991 VL 206 IS 4 BP 309 EP 314 DI 10.1016/0922-4106(91)90115-X PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FP344 UT WOS:A1991FP34400008 PM 1655489 ER PT J AU SEPPALA, R TIETZE, F KRASNEWICH, D WEISS, P ASHWELL, G BARSH, G THOMAS, GH PACKMAN, S GAHL, WA AF SEPPALA, R TIETZE, F KRASNEWICH, D WEISS, P ASHWELL, G BARSH, G THOMAS, GH PACKMAN, S GAHL, WA TI SIALIC-ACID METABOLISM IN SIALURIA FIBROBLASTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-ACETYLNEURAMINIC ACID; LYSOSOMAL STORAGE DISORDER; SALLA DISEASE; CHROMATOGRAPHY; EGRESS AB Sialuria is a rare inborn error of metabolism caused by excessive synthesis of sialic acid (N-acetylneuraminic acid, NeuAc). Fibroblasts cultured from the three known cases of sialuria contained 70-200-fold increases in soluble sialic acid, but normal concentrations of bound sialic acid. The sialic acid appeared in the cytosolic fraction of the cells on differential centrifugation, and was susceptible to borohydride reduction, suggesting that accumulated sialic acid was in the form of NeuAc and not CMP-NeuAc. In biochemical studies, CMP-NeuAc (50-mu-M) inhibited the UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase of normal fibroblasts by 84-100%, but inhibited the epimerase from sialuria cells by only 19-31%. Feeding sialuria cells up to 5mM D-glucosamine for 72 h increased free sialic acid content 20-60%, but normal cells were unaffected by this treatment. Cytidine feeding (5 mM, 72 h) reduced the NeuAc content of sialuria cells, initially 112, 104 and 266 nmol/mg protein, by 63-71 nmol/mg protein; CMP-NeuAc concentrations, initially 4,2, and 5 nmol/mg protein, increased by 14-33 nmol/mg protein. Consequently, the total cellular content of soluble sialic acid (NeuAc + CMP-NeuAc) was lowered 14-46% by cytidine feeding. The inheritance pattern of sialuria has not been determined. However, cells from both parents of one sialuria patient contained normal concentrations of free sialic acid, and the parental epimerase activity also responded normally to CMP-NeuAc. We conclude that the basic biochemical defect in all known cases of sialuria is a failure of CMP-NeuAc to feedback-inhibit UDP-GlcNAc 2-epimerase and cytidine feeding can lower the intracellular soluble sialic acid concentration of sialuria cells. C1 NIDDKD,MOLEC & CELL BIOL LAB,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,DIV MED GENET,SAN FRANCISCO,CA 94143. JOHNS HOPKINS UNIV,SCH MED,JOHN F KENNEDY INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. RP SEPPALA, R (reprint author), NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BETHESDA,MD 20892, USA. FU PHS HHS [10981] NR 22 TC 54 Z9 55 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 25 PY 1991 VL 266 IS 12 BP 7456 EP 7461 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FJ342 UT WOS:A1991FJ34200024 PM 2019577 ER PT J AU KAYASTHA, AM SAWA, Y NAGATA, S MILES, EW AF KAYASTHA, AM SAWA, Y NAGATA, S MILES, EW TI SITE-DIRECTED MUTAGENESIS OF THE BETA-SUBUNIT OF TRYPTOPHAN SYNTHASE FROM SALMONELLA-TYPHIMURIUM - ROLE OF ACTIVE-SITE GLUTAMIC ACID-350 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ULTRAVIOLET VISIBLE SPECTROSCOPY; SERINE O-SULFATE; ESCHERICHIA-COLI; ALPHA-SUBUNIT; PYRIDOXAL 5'-PHOSPHATE; CONFORMATIONAL-CHANGES; CIRCULAR-DICHROISM; CATALYTIC RESIDUE; SYNTHETASE; MECHANISM AB To investigate the functional role of glutamic acid 350 in the active site of the beta-subunit of tryptophan synthase from Salmonella typhimurium, we have replaced this residue by glutamine or alanine by use of site-directed mutagenesis. The mutant-alpha-2-beta-2 complexes were expressed, purified, crystallized, and characterized by spectroscopic and kinetic studies with several substrates. We find large alterations in the substrate and reaction specificity of each mutant form of the alpha-2-beta-2 complex. Since the two mutant enzymes are virtually inactive in reactions with L-serine but are active in reactions with beta-chloro-L-alanine, glutamic acid 350 may facilitate the beta-elimination of the weak hydroxyl leaving group of L-serine. The mutant-alpha-2-beta-2 complexes are more active than the wild type enzyme in the beta-elimination reaction with beta-chloro-L-alanine. These enzymes are irreversibly inactivated by beta-chloro-L-alanine, whereas the wild type enzyme is not. These altered properties may result from a change in the conformation of the active site, from a change in the orientation of the coenzyme relative to active site residues, or from a change in the solvent accessibility of the active site. The alteration in the active site may enhance the release of amino acrylate from the Schiff base intermediate by hydrolysis or by transamination. C1 NIDDKD, BIOCHEM PHARMACOL LAB, BLDG 8, RM 2A-09, BETHESDA, MD 20892 USA. NR 47 TC 22 Z9 22 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 APR 25 PY 1991 VL 266 IS 12 BP 7618 EP 7625 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FJ342 UT WOS:A1991FJ34200048 PM 1673461 ER PT J AU HEMPSTEAD, BL MARTINZANCA, D KAPLAN, DR PARADA, LF CHAO, MV AF HEMPSTEAD, BL MARTINZANCA, D KAPLAN, DR PARADA, LF CHAO, MV TI HIGH-AFFINITY NGF BINDING REQUIRES COEXPRESSION OF THE TRK PROTOONCOGENE AND THE LOW-AFFINITY NGF RECEPTOR SO NATURE LA English DT Article ID NERVE GROWTH-FACTOR; PC12 PHEOCHROMOCYTOMA CELLS; HUMAN NEURO-BLASTOMA; HUMAN-MELANOMA CELLS; NEUROTROPHIC FACTOR; RAT PHEOCHROMOCYTOMA; MOLECULAR-CLONING; GENE-TRANSFER; EXPRESSION; BRAIN AB Nerve growth factor (NGF) interacts with two different low-affinity receptors that can be distinguished by affinity crosslinking. Reconstitution experiments by membrane fusion and transient transfection into heterologous cells indicate that high-affinity NGF binding requires coexpression and binding to both the low-affinity NGF receptor and the tyrosine kinase trk gene product. These studies reveal a new growth factor receptor-mediated mechanism of cellular differentiation involving trk and the low-affinity NGF receptor. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC EMBRYOL GRP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. RP HEMPSTEAD, BL (reprint author), CORNELL UNIV,MED CTR,COLL MED,DEPT MED,DEPT CELL BIOL & ANAT,DIV HEMATOL ONCOL,1300 YORK AVE,NEW YORK,NY 10021, USA. RI Parada, luis/B-9400-2014 NR 79 TC 1059 Z9 1071 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 25 PY 1991 VL 350 IS 6320 BP 678 EP 683 DI 10.1038/350678a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FJ130 UT WOS:A1991FJ13000050 PM 1850821 ER PT J AU SCHMIDT, PJ NIEMAN, LK GROVER, GN MULLER, KL MERRIAM, GR RUBINOW, DR AF SCHMIDT, PJ NIEMAN, LK GROVER, GN MULLER, KL MERRIAM, GR RUBINOW, DR TI LACK OF EFFECT OF INDUCED MENSES ON SYMPTOMS IN WOMEN WITH PREMENSTRUAL-SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MENSTRUAL-CYCLE; PROLACTIN RESPONSES; ANTI-PROGESTERONE; TENSION SYNDROME; RU-486; MOOD; PITUITARY; HORMONES; PRIMATES AB Background. No physiologic abnormality of the luteal phase has been consistently demonstrated in women with premenstrual syndrome (PMS). Using the progesterone antagonist mifepristone, we truncated the late luteal phase of the menstrual cycle in a blinded fashion to evaluate the relation of the events of the late luteal phase to the symptoms of PMS. Methods. Fourteen women with PMS were given mifepristone (12.5 or 25 mg per kilogram of body weight) by mouth on the seventh day after the surge of luteinizing hormone. On the sixth through the eighth days after the surge, they also received injections of either placebo or human chorionic gonadotropin (2000 IU). Seven women with PMS received placebo instead of both mifepristone and human chorionic gonadotropin. All the women completed daily questionnaires measuring a variety of mood-related and somatic symptoms. Results. Mifepristone consistently induced menses. The women receiving only mifepristone had plasma progesterone levels like those of the follicular phase (< 3 nmol per liter) within four days, whereas all the other women had plasma progesterone levels characteristic of the luteal phase (> 8 nmol per liter) for at least seven days after treatment. In all three groups, the severity of symptoms was significantly higher after treatment than before, according to an analysis of variance with repeated measures. The level and pattern of the ratings of symptom severity were similar in all treatment groups. Conclusions. Neither the timing nor the severity of PMS symptoms was altered by mifepristone-induced menses or luteolysis. The temporal association of typical PMS symptoms with an artificially induced follicular phase suggests that endocrine events during the late luteal phase do not directly generate the symptoms of PMS. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP SCHMIDT, PJ (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BLDG 10,RM 3N238,BETHESDA,MD 20892, USA. NR 29 TC 115 Z9 116 U1 1 U2 6 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 25 PY 1991 VL 324 IS 17 BP 1174 EP 1179 DI 10.1056/NEJM199104253241705 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA FH572 UT WOS:A1991FH57200005 PM 2011161 ER PT J AU ZAMETKIN, A COHEN, RM AF ZAMETKIN, A COHEN, RM TI CEREBRAL GLUCOSE-METABOLISM IN HYPERACTIVITY - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ATTENTION DEFICIT DISORDER; DYSFUNCTION RP ZAMETKIN, A (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 25 PY 1991 VL 324 IS 17 BP 1216 EP 1217 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FH572 UT WOS:A1991FH57200022 ER PT J AU RHODES, C SAVAGNER, P LINE, S SASAKI, M CHIRIGOS, M DOEGE, K YAMADA, Y AF RHODES, C SAVAGNER, P LINE, S SASAKI, M CHIRIGOS, M DOEGE, K YAMADA, Y TI CHARACTERIZATION OF THE PROMOTER FOR THE RAT AND HUMAN LINK PROTEIN GENE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CARTILAGE PROTEOGLYCAN; CHLORAMPHENICOL ACETYLTRANSFERASE; 1ST INTRON; DNA; TRANSCRIPTION; EXPRESSION; CHONDROSARCOMA; IDENTIFICATION; HYBRIDIZATION; CHONDROCYTES AB We have isolated the 5'-end of the gene for the rat and human link protein by screening genomic libraries with oligonucleotides corresponding to the 5'-cDNA sequence. Several overlapping clones were isolated for the human link protein gene, while only one clone was obtained for the rat. All the clones contained a single exon of which the sequence was identical to the most 5'-end of the rat and human cDNAs. Transcription initiation sites for the rat link gene were identified by primer extension and S1 protection analysis using total RNA from the rat Swarm chondrosarcoma. Transcriptional initiation sites for the human link gene were determined by specific primer extension of RNA from human fetal cartilage. Comparison of 1500 bp of 5'-flanking sequence between the rat and human link protein genes showed strong sequence conservation near the start site of transcription with 80% overall identity. Analysis of the 5'-flanking regions also revealed a large inverted repeat consisting of repeating purine-pyrimidine, which has the potential to form left-handed Z-DNA. Transcriptional regulation of the link protein gene was studied by coupling either 7.0 kb or 0.85 kb of 5'-flanking rat DNA to the chloramphenicol acetyltransferase (CAT) gene followed by transfection into chick embryonic chondrocytes (CEC) and HeLa cells. Both constructs had considerable CAT activity in CEC cells and less activity in HeLa cells. Furthermore, inclusion of a DNA fragment from the first intron increased relative CAT activity in both of these cell types. The increased activity from the first intron was shown to be orientation independent in CEC. These results indicate the presence of positive cis-acting regulatory elements in both the promoter and first intron of the rat gene for link protein. RP RHODES, C (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. RI Line, Sergio/H-5272-2012 OI Line, Sergio/0000-0002-6574-9464 NR 47 TC 14 Z9 15 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 APR 25 PY 1991 VL 19 IS 8 BP 1933 EP 1939 DI 10.1093/nar/19.8.1933 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK282 UT WOS:A1991FK28200030 PM 2030970 ER PT J AU GELERNTER, J GEJMAN, PV BISIGHINI, S KIDD, KK AF GELERNTER, J GEJMAN, PV BISIGHINI, S KIDD, KK TI SEQUENCE TAGGED SITE (STS) TAQI RFLP AT DOPAMINE BETA-HYDROXYLASE (DBH) SO NUCLEIC ACIDS RESEARCH LA English DT Note ID GENE; LOCUS C1 VET ADM MED CTR,W HAVEN,CT 06516. NIMH,BETHESDA,MD 20892. RP GELERNTER, J (reprint author), YALE UNIV,SCH MED,DEPT HUMAN GENET,W SPRING ST,NEW HAVEN,CT 06510, USA. FU NIMH NIH HHS [MH30929, MH39239] NR 4 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 25 PY 1991 VL 19 IS 8 BP 1957 EP 1957 DI 10.1093/nar/19.8.1957 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK282 UT WOS:A1991FK28200046 PM 1674371 ER PT J AU DETERAWADLEIGH, SD ENCIO, IJ ROLLINS, DY COFFMAN, D WIESCH, D AF DETERAWADLEIGH, SD ENCIO, IJ ROLLINS, DY COFFMAN, D WIESCH, D TI A TTHIII1 POLYMORPHISM ON THE 5' FLANKING REGION OF THE GLUCOCORTICOID RECEPTOR GENE (GRL) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP DETERAWADLEIGH, SD (reprint author), NIMH,CLIN NEUROGENET BRANCH,9000 ROCKVILLE PIKE,BLDG 10-3N218,BETHESDA,MD 20892, USA. NR 3 TC 24 Z9 26 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 25 PY 1991 VL 19 IS 8 BP 1960 EP 1960 DI 10.1093/nar/19.8.1960-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK282 UT WOS:A1991FK28200052 PM 1674374 ER PT J AU POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR AF POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN DEBRISOQUINE 4-HYDROXYLASE (CYP2D) LOCUS SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, ROOM 131, 2700 MARTIN LUTHER KING AVE, WASHINGTON, DC 20032 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 25 PY 1991 VL 19 IS 8 BP 1961 EP 1961 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK282 UT WOS:A1991FK28200054 ER PT J AU POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN GENE OF THE LIGHT AND HEAVY-CHAINS OF MYELOPEROXIDASE GLYCOPROTEIN (MPO) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, ROOM 131, 2700 MARTIN LUTHER KING AVE, WASHINGTON, DC 20032 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 25 PY 1991 VL 19 IS 8 BP 1961 EP 1961 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FK282 UT WOS:A1991FK28200053 ER PT J AU MASTERS, BA WERNER, H ROBERTS, CT LEROITH, D RAIZADA, MK AF MASTERS, BA WERNER, H ROBERTS, CT LEROITH, D RAIZADA, MK TI INSULIN-LIKE GROWTH FACTOR-I (IGF-I) RECEPTORS AND IGF-I ACTION IN OLIGODENDROCYTES FROM RAT BRAINS SO REGULATORY PEPTIDES LA English DT Article DE IGF-I RECEPTOR; OLIGODENDROCYTE; GLIAL PROGENITOR; DIFFERENTIATION; MULTIPLICATION ID PROGENITOR CELLS; NERVOUS-SYSTEM; CULTURES; INVITRO AB Oligodendrocyte progenitor cells were prepared by mechanical dissociation of 1-day-old rat brain cultures. These cells undergo proliferation and differentiation into oligodendrocytes as demonstrated by the expression of proliferation and differentiation-related specific antigens. We have used this unique culture system to characterize insulin-like growth factor I (IGF-I) receptors and their action in the central nervous system (CNS). I-125-IGF-I specifically binds to these cultures with high affinity. Competition-inhibition data suggest that IGF-I is most potent in competing for I-125-IGF-I binding, followed by IGF-II and insulin. Scatchard analyses of the binding data indicate a curvilinear plot with a K(d) for high affinity of 0.2 nM, and a B(max) of 247 fmol/mg, and a K(d) for low affinity of 3.2 nM and B(max) of 1213 fmol/mg protein. Covalent cross-linking followed by SDS-PAGE analysis demonstrated a radioactive band of M(r) 135,000 which corresponds to the alpha subunit of the IGF-I receptor. Solution hybridization/RNase protection assay produced a single protected band corresponding to IGF-I receptor messenger RNA, further confirming the presence of these receptors. Incubation of progenitor cells with IGF-I resulted in a time- and concentration-dependent increase in [H-3]thymidine incorporation and cell numbers. This effect appears to be mediated by IGF-I receptors since IGF-II and insulin were proportionately less potent. In addition to its effect on proliferation, IGF-I also increased the number of 4E7- and GC-antigen positive cells. These observations indicate that oligodendrocytes in primary culture express specific IGF-I receptors and that the interaction of IGF-I with these receptors results in the proliferation as well as differentiation of oligodendrocytes. C1 UNIV FLORIDA,COLL MED,DEPT PHYSIOL,GAINESVILLE,FL 32610. NIDDKD,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BETHESDA,MD. OI Roberts, Charles/0000-0003-1756-5772 NR 23 TC 32 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD APR 25 PY 1991 VL 33 IS 2 BP 117 EP 131 DI 10.1016/0167-0115(91)90207-W PG 15 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA FL922 UT WOS:A1991FL92200004 PM 1652776 ER PT J AU WILLIAMS, TF AF WILLIAMS, TF TI THE HEALTH NEEDS OF OLDER HISPANICS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP WILLIAMS, TF (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 24 PY 1991 VL 265 IS 16 BP 2065 EP 2065 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FG907 UT WOS:A1991FG90700011 PM 2013921 ER PT J AU SELBY, JV NEWMAN, B QUIROGA, J CHRISTIAN, JC AUSTIN, MA FABSITZ, RR AF SELBY, JV NEWMAN, B QUIROGA, J CHRISTIAN, JC AUSTIN, MA FABSITZ, RR TI CONCORDANCE FOR DYSLIPIDEMIC HYPERTENSION IN MALE TWINS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-ARTERY DISEASE; RISK-FACTORS; INSULIN; PREVALENCE AB Sixty cases of dyslipidemic hypertension were identified in the 1028 middle-aged, white, male twin participants in the first examination of the National Heart, Lung, and Blood Institute Twin Study (1969 to 1973). The prevalence of dyslipidemic hypertension was similar by zygosity but proband concordance was three times greater in monozygotic than dizygotic twins (0.44 [seven concordant and 18 discordant pairs] vs 0.14 [two concordant and 24 discordant pairs]), suggesting a genetic effect on the condition. Low high-density lipoprotein cholesterol level was the most common lipid abnormality in concordant pairs. Mortality from ischemic heart disease was significantly higher in individuals with dyslipidemic hypertension. Obesity and glucose intolerance were closely associated with the syndrome. Moreover, within the 18 discordant monozygotic twin pairs, the twins with dyslipidemic hypertension had gained significantly more weight as adults and were significantly heavier than their unaffected cotwins. Thus, although genetic factors may influence development of dyslipidemic hypertension, nongenetic, potentially modifiable aspects of obesity are also closely related to expression of this clinically important syndrome. C1 VET AFFAIRS MED CTR,DEPT MED,LONG BEACH,CA. UNIV CALIF BERKELEY,SCH PUBL HLTH,DEPT EPIDEMIOL,BERKELEY,CA 94720. INDIANA UNIV,SCH MED,DEPT MED GENET,INDIANAPOLIS,IN 46202. UNIV WASHINGTON,SCH PUBL HLTH & COMMUNITY MED,DEPT EPIDEMIOL,SEATTLE,WA 98195. NHLBI,CLIN GENET & EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP SELBY, JV (reprint author), KAISER PERMANENTE MED CARE PROGRAM,DIV RES,NO CALIF REG,3451 PIEDMONT AVE,OAKLAND,CA 94611, USA. FU NHLBI NIH HHS [N01-HC55026] NR 25 TC 81 Z9 82 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 24 PY 1991 VL 265 IS 16 BP 2079 EP 2084 DI 10.1001/jama.265.16.2079 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA FG907 UT WOS:A1991FG90700024 PM 2013927 ER PT J AU RODGERS, GP AF RODGERS, GP TI RECENT APPROACHES TO THE TREATMENT OF SICKLE-CELL-ANEMIA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID FETAL-HEMOGLOBIN PRODUCTION; CLINICAL SEVERITY; HYDROXYUREA; DISEASE; 5-AZACYTIDINE; STIMULATION; AUGMENTATION; DETERMINANT; BABOONS RP RODGERS, GP (reprint author), NIDDKD,CHEM BIOL LAB,BLDG 10,ROOM 9N-318,BETHESDA,MD 20892, USA. NR 26 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 24 PY 1991 VL 265 IS 16 BP 2097 EP 2101 DI 10.1001/jama.265.16.2097 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA FG907 UT WOS:A1991FG90700028 PM 1707463 ER PT J AU WU, YN WAGNER, PD AF WU, YN WAGNER, PD TI CALPACTIN-DEPLETED CYTOSOLIC PROTEINS RESTORE CA2+-DEPENDENT SECRETION TO DIGITONIN-PERMEABILIZED BOVINE CHROMAFFIN CELLS SO FEBS LETTERS LA English DT Article DE SECRETION; CALPACTIN; CA2+; CHROMAFFIN CELL; CATECHOLAMINE ID CATECHOLAMINE SECRETION; PHOSPHOLIPID-BINDING; EXOCYTOSIS AB Incubation of digitonin-permeabilized bovine chromaffin cells results in a loss of Ca2+-dependent catecholamine secretion. The addition of cytosolic proteins prevents this loss of secretory activity. It has been proposed that calpactin might be the protein which is responsible for preventing this loss of activity. The experiments described in this paper show that cytosolic proteins which have been depleted of calpactin are as effective as control cytosolic proteins in preventing the loss of Ca2+-dependent secretion. Thus, a cytosolic protein(s) other than calpactin appears to be responsible for preventing this loss of secretory activity. RP WU, YN (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 12 TC 27 Z9 27 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 APR 22 PY 1991 VL 282 IS 1 BP 197 EP 199 DI 10.1016/0014-5793(91)80476-J PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FK098 UT WOS:A1991FK09800046 PM 1827411 ER PT J AU LESTER, BR WEINSTEIN, LS MCCARTHY, JB SUN, ZQ SMITH, RS FURCHT, LT AF LESTER, BR WEINSTEIN, LS MCCARTHY, JB SUN, ZQ SMITH, RS FURCHT, LT TI THE ROLE OF G-PROTEIN IN MATRIX-MEDIATED MOTILITY OF HIGHLY AND POORLY INVASIVE MELANOMA-CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GTP-BINDING PROTEIN; ISLET-ACTIVATING PROTEIN; PERTUSSIS-TOXIN; ADENYLATE-CYCLASE; METASTATIC PROPERTIES; MOLECULAR-CLONING; BASEMENT-MEMBRANE; PHOSPHOLIPASE-C; MURINE MELANOMA; ALPHA-SUBUNITS AB Membranes from 2 K1735 murine melanoma clones of high invasive capacity show increased amounts of pertussis toxin (PT) substrate when compared to a weakly invasive cellular counterpart. Using a panel of specific G-protein antibodies, we identified G(i-alpha-2) as the PT-sensitive G-protein uniquely abundant in highly invasive cells. In addition, RNA hybridization results confirm the immunoblot observations that G(i-alpha-2) is present at higher levels in strongly invasive cells. This result suggests that the elevated expression of G(i-alpha-2) in highly invasive cells is not entirely due to differences in either translational efficiency or protein degradation but is related to altered RNA transcriptional initiation, processing and/or degradation. ADP-ribosylation of G(i) alpha-subunits by PT inhibited the fibronectin, laminin and collagen type-IV-stimulated motility of the 2 highly invasive clones, while PT treatment of cells from a poorly invasive clone resulted in little or no reduction of the fibronectin, laminin or collagen type-IV-stimulated lower motility. Furthermore, PT treatment of highly or poorly invasive K1735 clones does not result in any alteration in cellular cAMP accumulation, suggesting that the PT substrate is not linked with the adenylyl cyclase enzyme complex. The data suggest that a PT-sensitive G-protein, probably G(i-alpha-2), regulates second messenger pathways that contribute to elevated motility in highly invasive K1735 cells. C1 UNIV MINNESOTA,SCH MED,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. NIH,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. RP LESTER, BR (reprint author), UNIV MINNESOTA,DIGHT LABS,400 CHURCH ST SE,MINNEAPOLIS,MN 55455, USA. RI Weinstein, Lee/I-5575-2015; OI Weinstein, Lee/0000-0002-1899-5152 FU NCI NIH HHS [CA29995, CA21643, CA43924] NR 54 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 22 PY 1991 VL 48 IS 1 BP 113 EP 120 PG 8 WC Oncology SC Oncology GA FH936 UT WOS:A1991FH93600020 PM 1850381 ER PT J AU BOUSSAOUD, D DESIMONE, R UNGERLEIDER, LG AF BOUSSAOUD, D DESIMONE, R UNGERLEIDER, LG TI VISUAL TOPOGRAPHY OF AREA TEO IN THE MACAQUE SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE TEMPORAL LOBE; VISUAL CORTEX; EXTRASTRIATE CORTEX; PATTERN VISION; MONKEY ID SUPERIOR TEMPORAL SULCUS; INTER-HEMISPHERIC CONNECTIONS; MONKEY AOTUS-TRIVIRGATUS; STRIATE PROJECTION ZONE; RHESUS-MONKEY; OWL MONKEY; VISUOTOPIC ORGANIZATION; FUNCTIONAL-PROPERTIES; CORTICAL CONNECTIONS; PRESTRIATE CORTEX AB Previous studies have mapped the visuotopic organization of visual areas from V1 through V4 in the occipital cortex and of area TE in the temporal cortex, but the cortex in between, at the occipito-temporal junction, has remained relatively unexplored. To determine the visuotopic organization of this region, receptive fields were mapped at 1,200 visually responsive sites on 370 penetrations in the ventral occipital and temporal cortex of five macaques. We identified a new visual area, roughly corresponding to cytoarchitectonic area TEO, located between the ventral portion of V4 and area TE. Receptive fields in TEO are intermediate in size between those in V4 and TE and have a coarse visuotopic organization. Collectively, receptive fields in TEO appear to cover nearly the entire contralateral visual field. The foveal and parafoveal representation of TEO is located laterally on the convexity of the inferior temporal gyrus, and the peripheral field is represented medially on the ventral surface of the hemisphere, within and medial to the occipitotemporal sulcus. Beyond the medial border of TEO, within cyteoarchitectonic area TF, is another visually responsive region, which we have termed VTF; this region may also have some crude visual topography. Bands of constant eccentricity in TEO appear to be continuous with those in V2,V3v, and V4. The upper field representation in TEO is located adjacent to that in ventral V4, with a representation of the horizontal meridian forming the boundary between the two areas. The lower field representation in TEO is located just anterior to the upper field but is smaller. In contrast to the orderly representation of eccentricity in TEO, we found little consistent representation of polar angle, other than the separation of upper and lower fields. The results of injecting anatomical tracers in two animals suggest that TEO is an important link in the pathway that relays visual information from V1 to the inferior temporal cortex. TEO is thus likely to play an important role in pattern perception. C1 NIMH,NEUROPSYCHOL LAB,BLDG 9,ROOM 1N107,BETHESDA,MD 20892. RI Boussaoud, Driss/B-6932-2008 NR 67 TC 299 Z9 299 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 22 PY 1991 VL 306 IS 4 BP 554 EP 575 DI 10.1002/cne.903060403 PG 22 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA FJ134 UT WOS:A1991FJ13400002 PM 1712794 ER EF