FN Thomson Reuters Web of Science™ VR 1.0 PT J AU SYKES, M SACHS, DH NIENHUIS, AW PEARSON, DA MOULTON, AD BODINE, DM AF SYKES, M SACHS, DH NIENHUIS, AW PEARSON, DA MOULTON, AD BODINE, DM TI SPECIFIC PROLONGATION OF SKIN-GRAFT SURVIVAL FOLLOWING RETROVIRAL TRANSDUCTION OF BONE-MARROW WITH AN ALLOGENEIC MAJOR HISTOCOMPATIBILITY COMPLEX GENE SO TRANSPLANTATION LA English DT Note ID CLASS-II GENE; HEMATOPOIETIC-CELLS; MONOCLONAL-ANTIBODIES; STEM-CELLS; EXPRESSION; TOLERANCE; MICE; TRANSPLANTS; REJECTION; LEUKEMIA AB Engrafted allogeneic hematopoietic cells have a unique capacity to induce a state of donor-specific transplantation tolerance across major histocompatibility complex barriers. This state allows permanent acceptance of donor-type organ grafts, with otherwise normal immunocompetence. We hypothesized that introduction of allogeneic MHC genes into autologous bone marrow which is then returned to recipient mice might similarly induce specific tolerance to products of the introduced MHC genes, without the risk of graft-vs-host disease. We demonstrate here that the introduction of MHC class I K(b) cDNA by retrovirus-mediated gene transfer into B10.AKM (K(k)) hematopoietic cells confers specific hyporesponsiveness to allogeneic skin grafts expressing K(b). C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. RP SYKES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT BIOL RES CTR,13TH ST,MGH E,BOSTON,MA 02114, USA. FU PHS HHS [N01-H1-19054] NR 35 TC 111 Z9 111 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN PY 1993 VL 55 IS 1 BP 197 EP 202 DI 10.1097/00007890-199301000-00037 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA KH660 UT WOS:A1993KH66000037 PM 8420048 ER PT B AU FRAKER, DL NORTON, JA AF FRAKER, DL NORTON, JA BE Fiers, W Buurman, WA TI THE ROLE OF TUMOR-NECROSIS-FACTOR IN THE TOXICITY AND THE ANTINEOPLASTIC ACTIVITY OF INTERLEUKIN-2 IMMUNOTHERAPY SO TUMOR NECROSIS FACTOR : MOLECULAR AND CELLULAR BIOLOGY AND CLINICAL RELEVANCE LA English DT Proceedings Paper CT 4TH INTERNATIONAL CONF ON TUMOUR NECROSIS FACTOR AND RELATED CYTOKINES CY MAY 02-06, 1992 CL VELDHOVEN, NETHERLANDS SP COMMISS EUROPEAN COMMUNITIES, CELLTECH RES, KNOLL, AMERSHAM, ARES SERONO, BASF BIORES, BAYER, BEHRINGWERKE, CHIBA FLOUR MILL, DAINIPPON PHARM RP FRAKER, DL (reprint author), NCI,SURG METAB SECT,SURG BRANCH,BLDG 10,ROOM 2BO7,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA BASEL BN 3-8055-5676-4 PY 1993 BP 221 EP 225 PG 5 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA BY26K UT WOS:A1993BY26K00031 ER PT J AU CILIAX, BJ KIRK, KL LEAPMAN, RD AF CILIAX, BJ KIRK, KL LEAPMAN, RD TI RADIATION-DAMAGE OF FLUORINATED ORGANIC-COMPOUNDS MEASURED BY PARALLEL ELECTRON-ENERGY LOSS SPECTROSCOPY SO ULTRAMICROSCOPY LA English DT Article ID MICROANALYSIS; CELLS AB The sensitivity of fluorinated organic compounds to radiation damage in the electron microscope was measured by electron energy loss spectroscopy (EELS). Five classes of molecules were investigated with fluorine atoms situated on: (1) an aliphatic chain, (2) an aromatic ring, (3) a trifluoromethyl group on an aromatic ring, (4) a trifluoromethyl group on a heterocyclic ring, and (5) a trifluoromethyl group next to a carbonyl group. The damage dose for fluorine loss was found to depend strongly on the position of the fluorine atoms and on specimen temperature. For poly-substituted fluorine on an aliphatic chain, approximately half of the fluorine was retained at doses in excess of 10(7) e/nm2. At room temperature molecules containing trifluoromethyl groups on aromatic or heterocyclic rings were much more sensitive to fluorine loss than compounds having fluorine substituted directly on the rings. This behavior is consistent with the relatively low chemical stability of the trifluoromethyl group in these structures. The rapid loss of fluorine at low electron doses (approximately 10(4) e/nm2) in the trifluoromethyl aromatic compounds was reduced several orders of magnitude by cooling the specimen to liquid-nitrogen temperatures. An understanding of how specific types of fluorinated compounds suffer damage under the electron beam will be important in their potential application as biochemical or pharmacological probes. C1 NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 34 TC 14 Z9 14 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3991 J9 ULTRAMICROSCOPY JI Ultramicroscopy PD JAN PY 1993 VL 48 IS 1-2 BP 13 EP 25 DI 10.1016/0304-3991(93)90167-V PG 13 WC Microscopy SC Microscopy GA KM788 UT WOS:A1993KM78800002 PM 8438530 ER PT B AU BROWNSTEIN, MJ LOLAIT, SJ AF BROWNSTEIN, MJ LOLAIT, SJ BE Gross, P Richter, D Robertson, GL TI HEREDITARY NEPHROGENIC DIABETES-INSIPIDUS SO VASOPRESSIN LA English DT Proceedings Paper CT 4TH INTERNATIONAL VASOPRESSIN CONF CY MAY 23-27, 1993 CL BERLIN, GERMANY RP BROWNSTEIN, MJ (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA MONTROUGE BN 2-7420-0031-3 PY 1993 BP 33 EP 43 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Pharmacology & Pharmacy; Physiology GA BZ35P UT WOS:A1993BZ35P00004 ER PT B AU KNEPPER, MA HAN, KS MAEDA, Y ECELBARGER, C DIGIOVANNI, S CHOU, CL NIELSEN, S WADE, JB AF KNEPPER, MA HAN, KS MAEDA, Y ECELBARGER, C DIGIOVANNI, S CHOU, CL NIELSEN, S WADE, JB BE Gross, P Richter, D Robertson, GL TI VASOPRESSIN-INDEPENDENT REGULATION OF COLLECTING DUCT WATER PERMEABILITY - LONG-TERM VERSUS SHORT-TERM FACTORS SO VASOPRESSIN LA English DT Proceedings Paper CT 4TH INTERNATIONAL VASOPRESSIN CONF CY MAY 23-27, 1993 CL BERLIN, GERMANY RP KNEPPER, MA (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA MONTROUGE BN 2-7420-0031-3 PY 1993 BP 381 EP 391 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Pharmacology & Pharmacy; Physiology GA BZ35P UT WOS:A1993BZ35P00032 ER PT J AU MARGOLIS, DM OSTROVE, JM STRAUS, SE AF MARGOLIS, DM OSTROVE, JM STRAUS, SE TI HSV-1 ACTIVATION OF HIV-1 TRANSCRIPTION IS AUGMENTED BY A CELLULAR PROTEIN THAT BINDS NEAR THE INITIATOR ELEMENT SO VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; TYPE-1; ENHANCER; DOMAINS; DNA; USF C1 NIAID,MED VIROL SECT,CLIN INVEST LAB,BLDG 10,ROOM 11N-228,BETHESDA,MD 20892. UNIV MASSACHUSETTS,MED CTR,PROGRAM MOLEC MED,WORCESTER,MA 01605. MICROBIOL ASSOCIATES INC,ROCKVILLE,MD 20850. OI Margolis, David/0000-0001-5714-0002 FU NIAID NIH HHS [AI31272, AI01027] NR 23 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 0042-6822 J9 VIROLOGY JI Virology PD JAN PY 1993 VL 192 IS 1 BP 370 EP 374 DI 10.1006/viro.1993.1046 PG 5 WC Virology SC Virology GA KC982 UT WOS:A1993KC98200046 PM 8390764 ER PT J AU KENNEDY, PE MOSS, B BERGER, EA AF KENNEDY, PE MOSS, B BERGER, EA TI PRIMARY HIV-1 ISOLATES REFRACTORY TO NEUTRALIZATION BY SOLUBLE CD4 ARE POTENTLY INHIBITED BY CD4-PSEUDOMONAS EXOTOXIN SO VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; INFECTED-CELLS; HYBRID PROTEIN; BINDING-AFFINITY; TYPE-1; GP120; INVITRO; DISSOCIATION; THERAPY C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 49 TC 17 Z9 18 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 JAN PY 1993 VL 192 IS 1 BP 375 EP 379 DI 10.1006/viro.1993.1047 PG 5 WC Virology SC Virology GA KC982 UT WOS:A1993KC98200047 PM 8517027 ER PT J AU BAIZER, JS DESIMONE, R UNGERLEIDER, LG AF BAIZER, JS DESIMONE, R UNGERLEIDER, LG TI COMPARISON OF SUBCORTICAL CONNECTIONS OF INFERIOR TEMPORAL AND POSTERIOR PARIETAL CORTEX IN MONKEYS SO VISUAL NEUROSCIENCE LA English DT Article DE CLAUSTRUM; PULVINAR; AMYGDALA; CAUDATE; PUTAMEN ID VISUAL CORTICAL AREAS; BEHAVING RHESUS-MONKEY; MACAQUE MONKEY; SUPERIOR COLLICULUS; HORSERADISH-PEROXIDASE; MACACA-MULATTA; PULVINAR NUCLEI; CORTICOSTRIATAL PROJECTIONS; CORTICOPONTINE PROJECTION; SUBSTANTIA INNOMINATA AB To investigate the subcortical connections of the object vision and spatial vision cortical processing pathways, we injected the inferior temporal and posterior parietal cortex of six Rhesus monkeys with retrograde or anterograde tracers. The temporal injections included area TE on the lateral surface of the hemisphere and adjacent portions of area TEO. The parietal injections covered the posterior bank of the intraparietal sulcus, including areas VIP and LIP. Our results indicate that several structures project to both the temporal and parietal cortex, including the medial and lateral pulvinar, claustrum, and nucleus basalis. However, the cells in both the pulvinar and claustrum that project to the two systems are mainly located in different parts of those structures, as are the terminals which arise from the temporal and parietal cortex. Likewise, the projections from the temporal and parietal cortex to the caudate nucleus and putamen are largely segregated. Finally, we found projections to the pons and superior colliculus from parietal but not temporal cortex, whereas we found the lateral basal and medial basal nuclei of the amygdala to be reciprocally connected with temporal but not parietal cortex. Thus, the results show that, like the cortical connections of the two visual processing systems, the subcortical connections are remarkably segregated. C1 NIMH,NEUROPSYCHOL LAB,BLDG 9,ROOM 1E104,BETHESDA,MD 20892. NR 95 TC 112 Z9 112 U1 2 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD JAN-FEB PY 1993 VL 10 IS 1 BP 59 EP 72 PG 14 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA KG297 UT WOS:A1993KG29700006 PM 8424928 ER PT J AU DESIMONE, R MORAN, J SCHEIN, SJ MISHKIN, M AF DESIMONE, R MORAN, J SCHEIN, SJ MISHKIN, M TI A ROLE FOR THE CORPUS-CALLOSUM IN VISUAL AREA V4 OF THE MACAQUE SO VISUAL NEUROSCIENCE LA English DT Article DE EXTRASTRIATE CORTEX; RECEPTIVE FIELDS; FIGURE-GROUND; COLOR CONSTANCY; VISUAL CORTEX ID CLASSICAL RECEPTIVE-FIELD; INFERIOR TEMPORAL CORTEX; RETINAL GANGLION-CELLS; RHESUS-MONKEY; CEREBRAL-CORTEX; VISUOTOPIC ORGANIZATION; SIMULTANEOUS CONTRAST; PRELUNATE GYRUS; SELECTIVE CELLS; NEURONS AB The classically defined receptive fields of V4 cells are confined almost entirely to the contralateral visual field. However, these receptive fields are often surrounded by large, silent suppressive regions, and stimulating the surrounds can cause a complete suppression of response to a simultaneously presented stimulus within the receptive field. We investigated whether the suppressive surrounds might extend across the midline into the ipsilateral visual field and, if so, whether the surrounds were dependent on the corpus callosum, which has a widespread distribution in V4. We found that the surrounds of more than half of the cells tested in the central visual field representation of V4 crossed into the ipsilateral visual field, with some extending up to at least 16 deg from the vertical meridian. Much of this suppression from the ipsilateral field was mediated by the corpus callosum, as section of the callosum dramatically reduced both the strength and extent of the surrounds. There remained, however, some residual suppression that was not further reduced by addition of an anterior commissure lesion. Because the residual ipsilateral suppression was similar in magnitude and extent to that found following section of the optic tract contralateral to the V4 recording, we concluded that it was retinal in origin. Using the same techniques employed in V4, we also mapped the ipsilateral extent of surrounds in the foveal representation of V1 in an intact monkey. Results were very similar to those in V4 following commissural or contralateral tract sections. The findings suggest that V4 is a central site for long-range interactions both within and across the two visual hemifields. Taken with previous work, the results are consistent with the notion that the large suppressive surrounds of V4 neurons contribute to the neural mechanisms of color constancy and figure-ground separation. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHOL,LOS ANGELES,CA 90024. RP DESIMONE, R (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 9,ROOM 1E104,BETHESDA,MD 20892, USA. FU NEI NIH HHS [R01 EY06096] NR 72 TC 65 Z9 65 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0952-5238 J9 VISUAL NEUROSCI JI Visual Neurosci. PD JAN-FEB PY 1993 VL 10 IS 1 BP 159 EP 171 PG 13 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA KG297 UT WOS:A1993KG29700012 PM 8424923 ER PT J AU RECHLER, MM AF RECHLER, MM TI INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS SO VITAMINS AND HORMONES, VOL 47 SE VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS LA English DT Review ID FACTOR IGF BINDING; FACTOR (IGF)-BINDING PROTEIN; MESSENGER-RIBONUCLEIC-ACID; FOLLICLE-STIMULATING-HORMONE; HUMAN-SKIN FIBROBLASTS; ADULT-RAT SERUM; IMMUNOREACTIVE SOMATOMEDIN-C; VASCULAR ENDOTHELIAL-CELLS; TISSUE-SPECIFIC EXPRESSION; ENDOMETRIAL STROMAL CELLS RP RECHLER, MM (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BETHESDA,MD 20892, USA. NR 352 TC 412 Z9 415 U1 1 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0083-6729 J9 VITAM HORM PY 1993 VL 47 BP 1 EP 114 DI 10.1016/S0083-6729(08)60444-6 PG 114 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BA09B UT WOS:A1993BA09B00001 PM 7680510 ER PT J AU LIANG, LF DEAN, J AF LIANG, LF DEAN, J TI OOCYTE DEVELOPMENT - MOLECULAR-BIOLOGY OF THE ZONA-PELLUCIDA SO VITAMINS AND HORMONES, VOL 47 SE VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS LA English DT Review ID PRIMORDIAL GERM-CELLS; SPERM RECEPTOR ACTIVITY; SEX-DETERMINING REGION; C-KIT RECEPTOR; FOLLICLE-STIMULATING-HORMONE; O-LINKED OLIGOSACCHARIDES; X-CHROMOSOME INACTIVATION; MOUSE GAMETE INTERACTIONS; TYROSINE KINASE RECEPTOR; MATERNAL MESSENGER-RNAS RP LIANG, LF (reprint author), NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 224 TC 10 Z9 10 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0083-6729 J9 VITAM HORM PY 1993 VL 47 BP 115 EP 159 DI 10.1016/S0083-6729(08)60445-8 PG 45 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BA09B UT WOS:A1993BA09B00002 PM 8447112 ER PT J AU KLEINMAN, HK WEEKS, BS SCHNAPER, HW KIBBEY, MC YAMAMURA, K GRANT, DS AF KLEINMAN, HK WEEKS, BS SCHNAPER, HW KIBBEY, MC YAMAMURA, K GRANT, DS TI THE LAMININS - A FAMILY OF BASEMENT-MEMBRANE GLYCOPROTEINS IMPORTANT IN CELL-DIFFERENTIATION AND TUMOR-METASTASES SO VITAMINS AND HORMONES, VOL 47 SE VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS LA English DT Review ID AMINO-ACID-SEQUENCE; A-CHAIN; EXTRACELLULAR-MATRIX; NEURITE OUTGROWTH; BINDING-PROTEIN; SYNTHETIC PEPTIDE; MULTIDOMAIN PROTEIN; SURFACE RECEPTORS; ENDOTHELIAL-CELLS; HUMAN CARCINOMA RP KLEINMAN, HK (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 106 TC 84 Z9 85 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0083-6729 J9 VITAM HORM PY 1993 VL 47 BP 161 EP 186 DI 10.1016/S0083-6729(08)60446-X PG 26 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BA09B UT WOS:A1993BA09B00003 PM 8447113 ER PT B AU WEINSTEIN, JN RUBINSTEIN, LV KOUTSOUKOS, AD KOHN, KW GREVER, MR MONKS, A SCUDIERO, DA WELCH, L CHIAUSA, AJ FOJO, AT VISWANADHAN, VN PAULL, KD AF WEINSTEIN, JN RUBINSTEIN, LV KOUTSOUKOS, AD KOHN, KW GREVER, MR MONKS, A SCUDIERO, DA WELCH, L CHIAUSA, AJ FOJO, AT VISWANADHAN, VN PAULL, KD GP INT NEURAL NETWORK SOC TI NEURAL NETWORKS IN THE DISCOVERY OF NEW TREATMENTS FOR CANCER AND AIDS SO WCNN'93 - PORTLAND, WORLD CONGRESS ON NEURAL NETWORKS, VOL I LA English DT Proceedings Paper CT World Congress on Neural Networks (WCNN 93, Portland) CY JUL 11-15, 1993 CL PORTLAND, OR SP INT NEURAL NETWORK SOC C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 BN 0-8058-1497-3 PY 1993 BP 111 EP 116 PG 6 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA BA45U UT WOS:A1993BA45U00028 ER PT B AU HIDARY, JD HSIAO, J LITMAN, R HONG, W PICKAR, D AF HIDARY, JD HSIAO, J LITMAN, R HONG, W PICKAR, D GP INT NEURAL NETWORK SOC TI NEURAL NETWORKS IN THE PATTERN-RECOGNITION ANALYSIS OF FUNCTIONAL BRAIN IMAGES SO WCNN'93 - PORTLAND, WORLD CONGRESS ON NEURAL NETWORKS, VOL IV LA English DT Proceedings Paper CT World Congress on Neural Networks (WCNN 93, Portland) CY JUL 11-15, 1993 CL PORTLAND, OR SP INT NEURAL NETWORK SOC C1 NIMH,ETB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 BN 0-8058-1497-3 PY 1993 BP 249 EP 251 PG 3 WC Computer Science, Artificial Intelligence; Neurosciences; Physics, Mathematical SC Computer Science; Neurosciences & Neurology; Physics GA BA45X UT WOS:A1993BA45X00053 ER PT J AU MATSUMOTO, Y SARKAR, G SOMMER, SS WICKNER, RB AF MATSUMOTO, Y SARKAR, G SOMMER, SS WICKNER, RB TI A YEAST ANTIVIRAL PROTEIN, SK1, SHARES A REPEATED AMINO-ACID-SEQUENCE PATTERN WITH BETA-SUBUNITS OF G-PROTEINS AND SEVERAL OTHER PROTEINS SO YEAST LA English DT Article DE DOUBLE-STRANDED RNA; KILLER SYSTEM; 20S RNA; MAK11; TPR REPEAT ID DOUBLE-STRANDED-RNA; NUCLEAR RIBONUCLEOPROTEIN PARTICLE; MAMMALIAN G-PROTEIN; SACCHAROMYCES-CEREVISIAE; GENE-PRODUCT; SUPERKILLER MUTATIONS; CATABOLITE REPRESSION; STRUCTURE PREDICTION; GLUCOSE REPRESSION; NEUROGENIC LOCUS AB SKI8 is a yeast antiviral gene, essential for controlling the propagation of M double-stranded RNA (dsRNA) and thus for preventing virus-induced cytopathology. Our DNA sequence of SKI8 shows that it encodes a 397 amino acid protein containing two copies of a 31 amino acid repeat pattern first identified in mammalian beta-transducin and Cdc4p of yeast. There are also four copies of this repeat in yeast Mak11p, necessary for M dsRNA propagation, and three copies in the putative product of the Dictyostelium AAC3 gene. Analysis of 36 cases of the repeat unit shows they have a consensus predicted structure: N-helix-sheet-turn-sheet-turn-sheet-helix-C. C1 NIDDK,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BLDG 8,ROOM 207,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,DEPT BIOCHEM & MOLEC BIOL,ROCHESTER,MN 55905. NR 59 TC 24 Z9 25 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD JAN PY 1993 VL 9 IS 1 BP 43 EP 51 DI 10.1002/yea.320090106 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA KL282 UT WOS:A1993KL28200005 PM 8442386 ER PT J AU LEYENDECKER, B AF LEYENDECKER, B TI INFLUENCE OF SIBLING ORDER ON DYADIC INTERACTIONS WITH 10-WEEK-OLD INFANTS SO ZEITSCHRIFT FUR ENTWICKLUNGSPSYCHOLOGIE UND PADAGOGISCHE PSYCHOLOGIE LA German DT Article ID MOTHER-INFANT; BEHAVIOR AB The daily environments of firstborn (N = 22) and laterborn infants (N = 18) at the age of ten weeks were assessed through 24-hour time budget analysis. Specifically, information was sought concerning the amount of time infants spend in dyadic interaction with a parent, by analysis of. the types of activities infants engage in on a given day, the presence of other persons during these activities, and time spent asleep versus time spent awake. The daily experiences of first- and laterborn infants differ significantly. In particular, laterborn infants have much less opportunity to spend time in dyadic interaction with their parents than do firstborns, and multiparous parents are similarily less involved in activities which afford dyadic interaction than are primiparous parents. The discussion addresses the question, wether the more prolonged periods of interaction between firstborns and their parents ultimately benefit laterborns by increasing parental experience, so that the reduced amount of time laterborns spend in dyadic interaction with their parents would be offset by the parental experience gained with firstborns. C1 NICHHD,BETHESDA,MD 20892. NR 50 TC 0 Z9 0 U1 2 U2 4 PU HOGREFE-VERLAG GMBH & CO PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0049-8637 J9 Z ENTWICKL PADAGOGIS JI Z. Entwicklung. Padag. Psychol. PY 1993 VL 25 IS 2 BP 164 EP 180 PG 17 WC Psychology, Educational SC Psychology GA KZ044 UT WOS:A1993KZ04400005 ER PT J AU CAPLAN, LJ HERRMANN, DJ AF CAPLAN, LJ HERRMANN, DJ TI SEMANTIC RELATIONS AS GRADED CONCEPTS SO ZEITSCHRIFT FUR PSYCHOLOGIE LA English DT Article DE SEMANTIC RELATIONS; REPRESENTATION OF SEMANTIC RELATIONS; CONCEPTUAL STRUCTURES ID SIMILARITY AB This experiment tests the hypothesis that semantic relations are graded concepts. It also tests the predictions of relation element theory and of Klix's (1986) theory of semantic relations regarding possible predictors of graded structure for semantic relations. Results support the hypothesis that semantic relations have graded structures, and indicate that differences among relations in gradedness reflect the families of semantic relations described by Chaffin & Herrmann (1984). In addition, Klix's distinction between property relations and event relations appears to be useful in explaining diffences among relations in graded structure. C1 NIMH,BETHESDA,MD 20892. NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. NR 18 TC 3 Z9 3 U1 0 U2 1 PU JOHANN AMBROSIUS BARTH VERLAG PI HEIDELBERG PA IM WEIHER 10, D-69121 HEIDELBERG, GERMANY SN 0044-3409 J9 Z PSYCHOL JI Z. Psychol. PY 1993 VL 201 IS 1 BP 85 EP 97 PG 13 WC Psychology, Multidisciplinary SC Psychology GA KX778 UT WOS:A1993KX77800007 PM 8098173 ER PT J AU BROWN, EW OLMSTED, RA MARTENSON, JS OBRIEN, SJ AF BROWN, EW OLMSTED, RA MARTENSON, JS OBRIEN, SJ TI EXPOSURE TO FIV AND FIPV IN WILD AND CAPTIVE CHEETAHS SO ZOO BIOLOGY LA English DT Article DE FELINE; RETROVIRUS; CORONAVIRUS AB Two RNA-containing viruses, feline infectious peritonitis virus (FIPV) and feline immunodeficiency virus (FIV), have been observed to infect cheetahs. Although both viruses cause lethal immunogenetic pathology in domestic cats, only FIPV has documented pathogenesis in cheetahs. We summarize and update here a worldwide survey of serum and plasma from cheetah and other nondomestic felids for antibodies to FIV and FIPV, based on Western blot and immunofluorescence assays. FIPV exposure shows an acute pattern with recognizable outbreaks in several zoological facilities, but is virtually nonexistent in sampled free-ranging populations of cheetahs. FIV is more endemic in certain natural cheetah populations, but infrequent in zoological collections. FIV exposure was also seen in lions, bobcats, leopards, snow leopards, and jaguars. FIV causes T-cell lymphocyte depletion and associated diseases in domestic cats, but there is little direct evidence for FIV pathology in exotic cats to date. Because of the parallels with a high incidence of simian immunodeficiency virus in free-ranging African primates without disease, the cat model may also reflect historic infections that have approached an evolutionary balance between the pathogen and immune defenses of their feline host species. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 0 TC 30 Z9 30 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 0733-3188 J9 ZOO BIOL JI Zoo Biol. PY 1993 VL 12 IS 1 BP 135 EP 142 DI 10.1002/zoo.1430120112 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA KR769 UT WOS:A1993KR76900011 ER PT J AU SEEFF, LB BUSKELLBALES, Z WRIGHT, EC DURAKO, SJ ALTER, HJ IBER, FL HOLLINGER, FB GITNICK, G KNODELL, RG PERRILLO, RP STEVENS, CE HOLLINGSWORTH, CG AF SEEFF, LB BUSKELLBALES, Z WRIGHT, EC DURAKO, SJ ALTER, HJ IBER, FL HOLLINGER, FB GITNICK, G KNODELL, RG PERRILLO, RP STEVENS, CE HOLLINGSWORTH, CG TI LONG-TERM MORTALITY AFTER TRANSFUSION-ASSOCIATED NON-A-HEPATITIS, NON-B-HEPATITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALCOHOLIC LIVER-DISEASE; C VIRUS; HEPATOCELLULAR-CARCINOMA; POSTTRANSFUSION HEPATITIS; FOLLOW-UP; VIRAL-HEPATITIS; PREVALENCE; ANTIBODIES; CIRRHOSIS; EFFICACY AB Background. Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known. Methods. We traced patients with transfusion-related non-A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980. We matched each patient with two control subjects (identified as the first and second controls) who received transfusions but who did not have hepatitis. The mortality rates in the three groups were determined with use of data from the National Death index and Social Security Death Tapes. Cause-specific mortality was determined by reviewing death certificates. Results. Vital status was established for over 94 percent of the 568 patients who had had non-A, non-B hepatitis and the two control groups (526 first controls and 458 second controls). After an average follow-up of 18 years, the estimate by life-table analysis of mortality from all causes was 51 percent for those with transfusion-associated non-A, non-B hepatitis, as compared with 52 percent for the first controls and 50 percent for the second controls. The survival curves for the three groups were virtually the same. Mortality related to liver disease was 3.3, 1.1, and 2.0 percent, respectively, among the three groups (P = 0.033 for the comparison of the group with non-A, non-B hepatitis with the combined control group). Seventy-one percent of the deaths related to liver disease occurred among patients with chronic alcoholism. Conclusions. In this long-term follow-up study, there was no increase in mortality from all causes after transfusion-associated non-A, non-B hepatitis, although there was a small but statistically significant increase in the number of deaths related to liver disease. C1 GEORGETOWN UNIV, SCH MED, WASHINGTON, DC USA. GEORGE WASHINGTON UNIV, CTR BIOSTAT, ROCKVILLE, MD USA. WESTAT CORP, ROCKVILLE, MD USA. NIH, BLOOD BANK, BETHESDA, MD 20892 USA. VET AFFAIRS MED CTR, HINES, IL USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA USA. UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. WASHINGTON UNIV, SCH MED, ST LOUIS, MO 63110 USA. NEW YORK BLOOD CTR, NEW YORK, NY 10021 USA. NHLBI, BETHESDA, MD 20892 USA. RP SEEFF, LB (reprint author), VET AFFAIRS MED CTR, 50 IRVING ST NW, WASHINGTON, DC 20422 USA. RI Jepsen, Peter/A-2593-2010 OI Jepsen, Peter/0000-0002-6641-1430 FU NHLBI NIH HHS [N01-HB-87047] NR 33 TC 650 Z9 654 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 31 PY 1992 VL 327 IS 27 BP 1906 EP 1911 DI 10.1056/NEJM199212313272703 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA KE505 UT WOS:A1992KE50500003 PM 1454085 ER PT J AU KOSUGI, S BAN, T AKAMIZU, T KOHN, LD AF KOSUGI, S BAN, T AKAMIZU, T KOHN, LD TI ROLE OF CYSTEINE RESIDUES IN THE EXTRACELLULAR DOMAIN AND EXOPLASMIC LOOPS OF THE TRANSMEMBRANE DOMAIN OF THE TSH RECEPTOR - EFFECT OF MUTATION TO SERINE ON TSH RECEPTOR ACTIVITY AND RESPONSE TO THYROID STIMULATING AUTOANTIBODIES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SITE-DIRECTED MUTAGENESIS; HUMAN THYROTROPIN RECEPTOR; LIGAND-BINDING; ADRENERGIC-RECEPTORS; GONADOTROPIN RECEPTORS; PROTEINS; IDENTIFICATION; EXPRESSION; DISEASE; SYSTEMS C1 KYOTO UNIV,SCH MED,DEPT LAB MED,SAKYO KU,KYOTO 606,JAPAN. RP KOSUGI, S (reprint author), NIDDKD,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892, USA. NR 22 TC 45 Z9 46 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 DEC 30 PY 1992 VL 189 IS 3 BP 1754 EP 1762 DI 10.1016/0006-291X(92)90281-O PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KF545 UT WOS:A1992KF54500074 PM 1336379 ER PT J AU LANE, MA INGRAM, DK CUTLER, RG KNAPKA, JJ BARNARD, DE ROTH, GS AF LANE, MA INGRAM, DK CUTLER, RG KNAPKA, JJ BARNARD, DE ROTH, GS TI DIETARY RESTRICTION IN NONHUMAN-PRIMATES - PROGRESS REPORT ON THE NIA STUDY SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID MUSCULOSKELETAL SYSTEM; RHESUS-MONKEYS; AGE C1 NIH,NATL CTR RES RESOURCES,SCI SERV BRANCH,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP LANE, MA (reprint author), NIA,FRANCIS SCOTT KEY MED CTR,GERONTOL RES CTR,NATHAN W SHOCK LABS,BALTIMORE,MD 21224, USA. NR 13 TC 55 Z9 56 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 DEC 26 PY 1992 VL 673 BP 36 EP 45 DI 10.1111/j.1749-6632.1992.tb27434.x PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KJ586 UT WOS:A1992KJ58600006 PM 1485732 ER PT J AU XIAO, RP LAKATTA, EG AF XIAO, RP LAKATTA, EG TI DETERIORATION OF BETA-ADRENERGIC MODULATION OF CARDIOVASCULAR FUNCTION WITH AGING SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CONGESTIVE-HEART-FAILURE; AGE-ASSOCIATED DECREASE; ADENYLATE-CYCLASE SYSTEM; VASCULAR SMOOTH-MUSCLE; CYCLIC-AMP; RAT MYOCARDIUM; PHOSPHOLAMBAN PHOSPHORYLATION; HOMOLOGOUS DESENSITIZATION; SARCOPLASMIC-RETICULUM; PLASMA-CATECHOLAMINES C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 97 TC 32 Z9 32 U1 0 U2 3 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 DEC 26 PY 1992 VL 673 BP 293 EP 310 DI 10.1111/j.1749-6632.1992.tb27465.x PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KJ586 UT WOS:A1992KJ58600037 PM 1336647 ER PT J AU VOGEL, SS CHERNOMORDIK, LV ZIMMERBERG, J AF VOGEL, SS CHERNOMORDIK, LV ZIMMERBERG, J TI CALCIUM-TRIGGERED FUSION OF EXOCYTOTIC GRANULES REQUIRES PROTEINS IN ONLY ONE MEMBRANE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SEA-URCHIN EGGS; PH-DEPENDENT FUSION; PLASMA-MEMBRANE; INFLUENZA-VIRUS; RECONSTITUTION; MECHANISMS; LIPOSOMES; RELEASE; CELL AB We studied calcium-triggered fusion of sea urchin egg secretory granules to test whether membrane bound fusion proteins are required in both fusing membranes. Using both light scattering assays and video microscopy, we found that native granules fused to granules that had been inactivated with either trypsin or N-ethylmaleimide. Granules also fused with liposomes prepared from lipids extracted from egg cortices and with liposomes made from synthetic phospholipids and cholesterol. Granule-liposome fusion required no cytoplasmic proteins and was inhibited by N-ethylmaleimide. Thus, membrane fusion of exocytotic granules can be promoted by proteins residing on only one of the two membranes. RP VOGEL, SS (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 6C-101,BETHESDA,MD 20892, USA. RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 30 TC 49 Z9 49 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 DEC 25 PY 1992 VL 267 IS 36 BP 25640 EP 25643 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KD073 UT WOS:A1992KD07300006 PM 1464584 ER PT J AU AHMED, SA CLAIBORNE, A AF AHMED, SA CLAIBORNE, A TI CATALYTIC PROPERTIES OF STREPTOCOCCAL NADH OXIDASE CONTAINING ARTIFICIAL FLAVINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PARA-HYDROXYBENZOATE HYDROXYLASE; ACTIVE-SITE PROBES; LACTATE OXIDASE; FAECALIS 10C1; FLAVOPROTEIN; PEROXIDASE; OXYGEN; REDUCTASE; MECHANISM; REACTIVITY AB The flavoprotein NADH oxidase from Streptococcus faecalis 10C1, which catalyzes the tetravalent reduction of O2 --> 2H2O, has been purified as the apoenzyme to allow reconstitution studies with both native and artificial flavins. Turnover numbers for the enzyme containing 1-deaza-, 2-thio-, and 4-thio-FAD range from 51 to 4% of that of the native FAD enzyme; these reconstituted oxidases also catalyze the four-electron reduction of oxygen. Dithionite and NADH titrations of the native FAD oxidase require 1.7 eq of reductant/FAD and follow spectral courses very similar to those previously reported for the purified holoenzyme. Azide is a linear mixed-type inhibitor with respect to NADH, and dithionite titrations in the presence of azide yield significant stabilization of the neutral blue semiquinone. Redox stoichiometries for the oxidase containing modified flavins range from 1.1 to 1.4 eq of reductant/FAD. Spectrally distinct reduced enzyme . NAD+ complexes result with all but the 2-thio-FAD enzyme on titration with NADH. The reduced 4-thio-FAD oxidase shows little or no evidence of desulfurization to native FAD on reduction and reoxidation. Both the 8-mercapto- (E'0 = -290 mV) and 8-hydroxy-FAD (E'0 = -335 m/V) oxidases are readily reduced by excess NADH. These results offer a further basis for analysis of the active-site structure and oxygen reactivity of this unique flavoprotein oxidase. C1 WAKE FOREST UNIV,MED CTR,DEPT BIOCHEM,WINSTON SALEM,NC 27157. RP AHMED, SA (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM-35394] NR 42 TC 8 Z9 8 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 DEC 25 PY 1992 VL 267 IS 36 BP 25822 EP 25829 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KD073 UT WOS:A1992KD07300039 PM 1464596 ER PT J AU KRATZKE, RA OTTERSON, GA LIN, AY SHIMIZU, E ALEXANDROVA, N ZAJAC-KAYE, M HOROWITZ, JM KAYE, FJ AF KRATZKE, RA OTTERSON, GA LIN, AY SHIMIZU, E ALEXANDROVA, N ZAJAC-KAYE, M HOROWITZ, JM KAYE, FJ TI FUNCTIONAL-ANALYSIS AT THE CYS(706) RESIDUE OF THE RETINOBLASTOMA PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LARGE-T-ANTIGEN; TUMOR SUPPRESSOR GENES; CARCINOMA CELL-LINES; SUSCEPTIBILITY GENE; TRANSCRIPTION FACTOR; LEUCINE REPEATS; RB PROTEIN; PRODUCT; BINDING; EXPRESSION AB A missense mutation at cysteine 706, resulting in a retinoblastoma (RB) protein defective in phosphorylation and oncoprotein binding, has been isolated from a human tumor cell line. Since this residue is conserved in murine RB and in the related p107 protein, we studied the activity of in vitro mutants flanking this position. These experiments demonstrated that the thiol atom at codon 706 does not possess intrinsic functional activity as small polar or nonpolar residues could substitute at either codons 706 or 707, while bulkier R-group changes in these positions interfered with in vitro oncoprotein binding or in vivo protein phosphorylation. A series of missense mutants in an adjacent leucine repeat domain also demonstrated a loss of oncoprotein binding that was proportional to the magnitude of amino acid substitutions. To determine whether the cysteine 706 --> phenylalanine RB mutant retained any protein binding activity, we examined its ability to precipitate MYC, which was recently identified as a potential RB-associated protein. These experiments demonstrated that the mutant RB product is capable of binding in vitro to c-myc and L-myc proteins with comparable affinity as wild-type RB. These findings raise questions about the functional role of the RB:MYC interactions and emphasize important differences in the binding patterns between MYC and the other RB-associated proteins. C1 NCI, NAVY ONCOL BRANCH, BETHESDA, MD 20889 USA. NCI, MED BRANCH, BETHESDA, MD 20889 USA. DUKE UNIV, MED CTR, CELL GROWTH REGULAT & ONCOGENESIS SECT, DURHAM, NC 27710 USA. DUKE UNIV, MED CTR, DEPT MICROBIOL & IMMUNOL, DURHAM, NC 27710 USA. RP KAYE, FJ (reprint author), USN HOSP, NCI, NAVY MED ONCOL BRANCH, BLDG 8, RM 5101, BETHESDA, MD 20889 USA. RI kaye, frederic/E-2437-2011 FU NCI NIH HHS [CA53248] NR 50 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 DEC 25 PY 1992 VL 267 IS 36 BP 25998 EP 26003 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KD073 UT WOS:A1992KD07300062 PM 1334491 ER PT J AU LI, YS HOFFMAN, RM LEBEAU, MM ESPINOSA, R JENKINS, NA GILBERT, DJ COPELAND, NG DEUEL, TF AF LI, YS HOFFMAN, RM LEBEAU, MM ESPINOSA, R JENKINS, NA GILBERT, DJ COPELAND, NG DEUEL, TF TI CHARACTERIZATION OF THE HUMAN PLEIOTROPHIN GENE - PROMOTER REGION AND CHROMOSOMAL LOCALIZATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; FIBROBLAST GROWTH-FACTORS; HEPARIN-BINDING-PROTEIN; RETINOIC ACID; MOUSE EMBRYOGENESIS; IDENTIFICATION; DISTINCT; DIFFERENTIATION; PURIFICATION; ORGANIZATION AB The protein (PTN) encoded by the pleiotrophin (PTN) gene belongs to a recently described family of heparin-binding cytokines whose expression is temporally and spatially regulated during development. We have now isolated genomic clones of the human PTN gene, characterized its promoter region, determined its transcription initiation site(s), and established functional activity of the PTN promoter. A fragment -550/+191 that contains a CAAT box, no apparent TATA box, and four consensus sites for the binding of MyoD is sufficient to provide optimal promoter activity. A serum response element is found at -559 to -568. We also have identified the human PTN gene on chromosome 7, band q33 and the mouse Ptn gene on chromosome 6, respectively. The data thus identify and characterize the 5' end of the PTN gene and its promoter region, suggest potential regions that may contribute to the regulation of its transcriptional activity, and localize the PTN gene in human and mouse chromosomes. C1 WASHINGTON UNIV,JEWISH HOSP ST LOUIS,SCH MED,DEPT BIOCHEM & MOLEC BIOPHYS,ST LOUIS,MO 63110. UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP LI, YS (reprint author), WASHINGTON UNIV,JEWISH HOSP ST LOUIS,SCH MED,DEPT MED,ST LOUIS,MO 63110, USA. FU NCI NIH HHS [CA49712]; NHLBI NIH HHS [HL14147, HL31102] NR 34 TC 58 Z9 62 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 DEC 25 PY 1992 VL 267 IS 36 BP 26011 EP 26016 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KD073 UT WOS:A1992KD07300064 PM 1464612 ER PT J AU CAPPS, DB DUNBAR, J KESTEN, SR SHILLIS, J WERBEL, LM PLOWMAN, J WARD, DL AF CAPPS, DB DUNBAR, J KESTEN, SR SHILLIS, J WERBEL, LM PLOWMAN, J WARD, DL TI 2-(AMINOALKYL)-5-NITROPYRAZOLO[3,4,5-KL]ACRIDINES, A NEW CLASS OF ANTICANCER AGENTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PYRAZOLOACRIDINES; TUMORS AB 2-(Aminoalkyl)-5-nitropyrazolo[3,4,5-kl]acridines were prepared from substituted anilines via the 1-chloro-4-nitroacridones followed by condensation with [(alkylamino)alkyl]hydrazines. Impressive activity was demonstrated for the 9-hydroxy, 9-alkoxy, and 9-acyloxy analogs in vitro on a L1210 leukemia line and in vivo against the P388 leukemia. Advanced studies led to the selection of 3bbb for clinical trial. C1 WARNER LAMBERT PARKE DAVIS,PHARMACEUT RES,ANN ARBOR,MI 48106. NCI,DIV CANC TREATMENT,BETHESDA,MD 20205. MICHIGAN STATE UNIV,DEPT CHEM,E LANSING,MI 48824. NR 23 TC 48 Z9 49 U1 2 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 DEC 25 PY 1992 VL 35 IS 26 BP 4770 EP 4778 DI 10.1021/jm00104a001 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KE869 UT WOS:A1992KE86900001 PM 1479579 ER PT J AU TAN, GT WICKRAMASINGHE, A VERMA, S SINGH, R HUGHES, SH PEZZUTO, JM BABA, M MOHAN, P AF TAN, GT WICKRAMASINGHE, A VERMA, S SINGH, R HUGHES, SH PEZZUTO, JM BABA, M MOHAN, P TI POTENTIAL ANTI-AIDS NAPHTHALENESULFONIC ACID-DERIVATIVES - SYNTHESIS AND INHIBITION OF HIV-1 INDUCED CYTOPATHOGENESIS AND HIV-1 AND HIV-2 REVERSE-TRANSCRIPTASE ACTIVITIES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RIBONUCLEASE-H DOMAIN; VIRUS TYPE-1 HIV-1; ESCHERICHIA-COLI; SELECTIVE-INHIBITION; ANTI-HIV-1 ACTIVITY; ANTIVIRAL ACTIVITY; REPLICATION; COMPOUND; ANALOGS; SURAMIN AB Several naphthalenedi- and trisulfonic acids have been synthesized and evaluated for inhibitory potential against cytopathogenesis and purified recombinant human immunodeficiency virus type 1(HIV-1) and type 2 (HIV-2) reverse transcriptase (RT). The most potent derivative that emerged from the anti-RT study was a small molecule 6 (MW = 840), a dipalmitoylated derivative of 2,7-naphthalenedisulfonic acid. Analog 6 demonstrated 50 % inhibitory concentration (IC50) values of 2.42 and 0.86 muM for HIV-1 and HIV-2 RT, respectively. The second most active compound was also a derivative of the same naphthalenedisulfonic acid but contained only one palmitoyl moiety. This compound 9 displayed IC50 values of 4.8 and 3.7 muM for HIV-1 and HIV-2 RT, respectively. Both analogs 6 and 9 are active at noncytotoxic doses, exhibits lightly higher potencies for the RT of HIV-2 over HIV-1, and demonstrate activities superior to the hexasulfonic acid derivative suramin (IC50 values of 9.4 and 15.5 muM for HIV-1 and HIV-2 RT, respectively). In the cytopathogenesis assay, the most active compound is a bis naphthalenedisulfonic acid derivative 17, containing a flexible octamethylene spacer and exhibiting an in vitro therapeutic index of 29.7. Most striking, however, is the influence of the palmitoyl functionality in the naphthalenedisulfonic acid series to confer activity against both HIV-1 and HIV-2 RT. C1 UNIV ILLINOIS,COLL PHARM,DEPT MED CHEM & PHARMACOGNOSY,CHICAGO,IL 60680. ABL INC,BASIC RES PROGRAM,NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. FUKUSHIMA MED SCH,DEPT MICROBIOL,FUKUSHIMA 96012,JAPAN. UNIV ILLINOIS,COLL PHARM,PROGRAM COLLABORAT RES PHARMACEUT SCI,CHICAGO,IL 60680. UNIV ILLINOIS,SPECIALIZED CANC CTR,CHICAGO,IL 60680. RI Baba, Masanori/G-3867-2011 FU NCI NIH HHS [N01-CO-74101] NR 34 TC 29 Z9 30 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 DEC 25 PY 1992 VL 35 IS 26 BP 4846 EP 4853 DI 10.1021/jm00104a010 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KE869 UT WOS:A1992KE86900010 PM 1282569 ER PT J AU GONG, DW HASEGAWA, S WADA, K ROEDER, RG NAKATANI, Y HORIKOSHI, M AF GONG, DW HASEGAWA, S WADA, K ROEDER, RG NAKATANI, Y HORIKOSHI, M TI ELUCIDATION OF 3 PUTATIVE STRUCTURAL SUBDOMAINS BY COMPARISON OF PRIMARY STRUCTURE OF XENOPUS AND HUMAN RAP74 SO NUCLEIC ACIDS RESEARCH LA English DT Note ID RNA POLYMERASE-II; TRANSCRIPTION C1 ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. NIDCD,NEUROCHEM LAB,BETHESDA,MD 20892. UNIV TOKYO,INST APPL MICROBIOL,BUNKYO KU,TOKYO 113,JAPAN. NR 5 TC 11 Z9 12 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 DEC 25 PY 1992 VL 20 IS 24 BP 6736 EP 6736 DI 10.1093/nar/20.24.6736 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KG705 UT WOS:A1992KG70500042 PM 1480494 ER PT J AU SCHWARTZ, RH AF SCHWARTZ, RH TI COSTIMULATION OF LYMPHOCYTES-T - THE ROLE OF CD28, CTLA-4, AND B7/BB1 IN INTERLEUKIN-2 PRODUCTION AND IMMUNOTHERAPY SO CELL LA English DT Review ID ACTIVATION ANTIGEN-B7; EXPRESSION RP SCHWARTZ, RH (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 22 TC 1164 Z9 1171 U1 5 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 24 PY 1992 VL 71 IS 7 BP 1065 EP 1068 DI 10.1016/S0092-8674(05)80055-8 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KE604 UT WOS:A1992KE60400001 PM 1335362 ER PT J AU HARDY, WD FEINBERG, J FINKELSTEIN, DM POWER, ME HE, W KACZKA, C FRAME, PT HOLMES, M WASKIN, H FASS, RJ POWDERLY, WG STEIGBIGEL, RT ZUGER, A HOLZMAN, RS AF HARDY, WD FEINBERG, J FINKELSTEIN, DM POWER, ME HE, W KACZKA, C FRAME, PT HOLMES, M WASKIN, H FASS, RJ POWDERLY, WG STEIGBIGEL, RT ZUGER, A HOLZMAN, RS TI A CONTROLLED TRIAL OF TRIMETHOPRIM SULFAMETHOXAZOLE OR AEROSOLIZED PENTAMIDINE FOR SECONDARY PROPHYLAXIS OF PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME - AIDS CLINICAL-TRIALS GROUP PROTOCOL-021 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VIRUS INFECTION; CHEMOPROPHYLAXIS; ZIDOVUDINE AB Background. Pneumocystis carinii pneumonia (PCP) continues to be the most common index diagnosis in the acquired immunodeficiency syndrome (AIDS), but it is not clear which of several available agents is the most effective in preventing a recurrence of PCP. Methods. We conducted a comparative, open-label trial in 310 adults with AIDS who had recently recovered from an initial episode of PCP and had no treatment-limiting toxic effects of trimethoprim-sulfamethoxazole or pentamidine. All the patients were treated with zidovudine and were randomly assigned to receive either 800 mg of sulfamethoxazole and 160 mg of trimethoprim once daily or 300 mg of aerosolized pentamidine administered every four weeks by jet nebulizer. The participants were followed for a median of 17.4 months. Results. In the trimethoprim-sulfamethoxazole group (n = 154) there were 14 recurrences of PCP, as compared with 36 recurrences (including 1 extrapulmonary recurrence) in the aerosolized-pentamidine group (n = 156). The estimated recurrence rates at 18 months were 11.4 percent with trimethoprim-sulfamethoxazole and 27.6 percent with pentamidine (P<0.001). The risk of a recurrence (adjusted for initial CD4 cell count) was 3.25 times higher in the pentamidine group (P<0.001; 95 percent confidence interval, 1.72 to 6.16). There were no significant differences between the groups in survival or in hematologic or hepatic toxicity. Crossovers from trimethoprim-sulfamethoxazole to aerosolized pentamidine were more common than the reverse (27 vs. 4 percent), partly because of the study protocols for the management of leukopenia. There were 19 serious bacterial infections in the trimethoprim-sulfamethoxazole group and 38 in the pentamidine group. The time to a first bacterial infection was significantly greater for those assigned to trimethoprim-sulfamethoxazole (P = 0.017). Conclusions. In patients with AIDS who are receiving zidovudine, trimethoprim-sulfamethoxazole is more effective than aerosolized pentamidine in conventional doses for the prevention of recurrent pneumocystis infection. C1 NYU,SCH MED,DEPT MED,550 1ST AVE,NEW YORK,NY 10016. UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. NIAID,DIV AIDS,BETHESDA,MD 20892. FRONTIER SCI TECHNOL & RES FDN,AMHERST,NY. UNIV CINCINNATI,SCH MED,DEPT MED,CINCINNATI,OH 45221. UNIV SO CALIF,DEPT MED,LOS ANGELES,CA 90089. DUKE UNIV,SCH MED,DEPT MED,DURHAM,NC 27706. OHIO STATE UNIV,COLL MED,DEPT MED,COLUMBUS,OH 43210. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. SUNY STONY BROOK,DEPT MED,STONY BROOK,NY 11794. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED,BRONX,NY 10461. RP HOLZMAN, RS (reprint author), NYU,SCH MED,DEPT MED,550 1ST AVE,NEW YORK,NY 10016, USA. FU NIAID NIH HHS [N01-AI-52607, N0-AI-95030] NR 18 TC 331 Z9 334 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 24 PY 1992 VL 327 IS 26 BP 1842 EP 1848 DI 10.1056/NEJM199212243272604 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KD714 UT WOS:A1992KD71400004 PM 1448121 ER PT J AU MASUR, H AF MASUR, H TI DRUG-THERAPY - PREVENTION AND TREATMENT OF PNEUMOCYSTIS PNEUMONIA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CARINII DIHYDROFOLATE-REDUCTASE; TRIMETHOPRIM-SULFAMETHOXAZOLE; AIDS PATIENTS; RANDOMIZED TRIAL; PENTAMIDINE ISETHIONATE; INTRAVENOUS PENTAMIDINE; AEROSOLIZED PENTAMIDINE; MARROW TRANSPLANTATION; HEART-TRANSPLANTATION RP MASUR, H (reprint author), NIMH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 111 TC 186 Z9 189 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 DEC 24 PY 1992 VL 327 IS 26 BP 1853 EP 1860 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA KD714 UT WOS:A1992KD71400006 PM 1448123 ER PT J AU CHRISTENSEN, RG MALONE, W AF CHRISTENSEN, RG MALONE, W TI DETERMINATION OF OLTIPRAZ IN SERUM BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH OPTICAL ABSORBENCY AND MASS-SPECTROMETRIC DETECTION SO JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS LA English DT Article AB Three methods have been developed for the analysis of Oltipraz in serum. A method suitable for routine use employs spiking with a homologous internal standard, off-line solid-phase extraction. high-performance liquid chromatographic separation, and optical absorbance detection at 450 nm. Method detection limit is about 1 ng/ml. A second method, less susceptible to bias from co-eluting interferences, uses a stable isotope-labeled internal standard, similar extraction and separation, and detection by thermospray mass spectrometry. Method detection limit is about 0.2 ng/ml. A third method was developed which can be used without specially synthesized internal standards. It uses on-line solid-phase extraction, with quantification by comparison with external standards. Method detection limit is about 3 ng/ml. Good agreement was observed between these methods and with similar and different methods run in other laboratories. Calibration curves were linear over the entire range which was investigated, i.e., up to 500 ng/ml. Coefficients of variation were similar for all three methods, being about 5%. C1 NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. RP CHRISTENSEN, RG (reprint author), NATL INST STAND & TECHNOL,CHEM SCI & TECHNOL LAB,DIV ORGAN ANALYT RES,222-B158,GAITHERSBURG,MD 20899, USA. FU NCI NIH HHS [Y01-CN-80655] NR 3 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR-BIOMED JI J. Chromatogr.-Biomed. Appl. PD DEC 23 PY 1992 VL 584 IS 2 BP 207 EP 212 DI 10.1016/0378-4347(92)80577-D PG 6 WC Chemistry, Analytical SC Chemistry GA KD797 UT WOS:A1992KD79700009 PM 1484105 ER PT J AU NAKAMURA, H YOSHIMURA, K BAJOCCHI, G TRAPNELL, BC PAVIRANI, A CRYSTAL, RG AF NAKAMURA, H YOSHIMURA, K BAJOCCHI, G TRAPNELL, BC PAVIRANI, A CRYSTAL, RG TI TUMOR-NECROSIS-FACTOR MODULATION OF EXPRESSION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE SO FEBS LETTERS LA English DT Article DE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; GENE EXPRESSION; TUMOR NECROSIS FACTOR-ALPHA; MESSENGER-RNA TRANSCRIPT; TRANSCRIPTION; MESSENGER-RNA STABILITY ID FACTOR-ALPHA; EPITHELIAL-CELLS; CHLORIDE CHANNEL; MESSENGER-RNA; COLLAGEN GENE; IDENTIFICATION; CFTR; CDNA; DNA; TNF AB Based on the knowledge that expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene can be modulated at the transcriptional level, and that the CFTR gene promoter contains sequences homologous to elements in other promoters that respond to tumor necrosis factor-alpha (TNF), we evaluated the hypothesis that TNF might modulate CFTR gene expression in epithelial cells. Studies with HT-29 cells, a colon epithelium-derived tumor cell line known to express the CFTR gene, demonstrated that TNF downregulated CFTR mRNA transcript levels in a dose- and time-dependent fashion. Interestingly, nuclear run-on analyses demonstrated that TNF did not affect the rate of transcription of CFTR gene, but exposure of the cells to TNF did modify the stability of CFTR mRNA transcripts, resulting in a mRNA half-life that was reduced to 65% of the resting level. These observations suggest that CFTR gene expression can be modulated by TNF, at least in part, at the post-post-transcriptional level. C1 NHLBI,PULM BRANCH BLDG 10,ROOM 6D03,BETHESDA,MD 20892. TRANSGENE SA,F-67000 STRASBOURG,FRANCE. NR 41 TC 38 Z9 39 U1 0 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 DEC 21 PY 1992 VL 314 IS 3 BP 366 EP 370 DI 10.1016/0014-5793(92)81507-I PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA KD507 UT WOS:A1992KD50700036 PM 1281791 ER PT J AU SEETHARAM, S SEIDMAN, MM AF SEETHARAM, S SEIDMAN, MM TI MODULATION OF ULTRAVIOLET-LIGHT MUTATIONAL HOTSPOTS BY CELLULAR STRESS SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE MUTATION SPECTRA; SHUTTLE VECTOR; XERODERMA PIGMENTOSUM; HOTSPOT VARIABILITY ID SHUTTLE VECTOR PLASMID; XERODERMA-PIGMENTOSUM; MAMMALIAN-CELLS; DNA-POLYMERASE; SPECTRUM; MUTAGENESIS; FIBROBLASTS; EXPRESSION; DAMAGE; REPAIR C1 OTSUKA PHARMACEUT CO LTD,9900 MED CTR DR,ROCKVILLE,MD 20850. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 25 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 20 PY 1992 VL 228 IS 4 BP 1031 EP 1036 DI 10.1016/0022-2836(92)90311-7 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KE602 UT WOS:A1992KE60200002 PM 1474574 ER PT J AU NICKOL, J RAU, DC AF NICKOL, J RAU, DC TI ZINC INDUCES A BEND WITHIN THE TRANSCRIPTION FACTOR-IIIA-BINDING REGION OF THE 5-S RNA GENE SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ELECTRIC BIREFRINGENCE; 5-S RNA GENE; BENT DNA; ZN-BINDING ID ANTITUMOR DRUG CIS-DIAMMINEDICHLOROPLATINUM(II); DIRECTS SPECIFIC INITIATION; XENOPUS 5S-RNA GENE; STRUCTURAL POLYMORPHISM; ELECTRIC BIREFRINGENCE; MULTIPLE FACTORS; POLYMERASE-III; FACTOR-TFIIIA; MAJOR GROOVE; DNA BENDS C1 NIDDKD,BIOCHEM METAB LAB,BETHESDA,MD 20892. RP NICKOL, J (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 51 TC 32 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 20 PY 1992 VL 228 IS 4 BP 1115 EP 1123 DI 10.1016/0022-2836(92)90319-F PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KE602 UT WOS:A1992KE60200010 PM 1474581 ER PT J AU STEPHENS, RM SCHNEIDER, TD AF STEPHENS, RM SCHNEIDER, TD TI FEATURES OF SPLICEOSOME EVOLUTION AND FUNCTION INFERRED FROM AN ANALYSIS OF THE INFORMATION AT HUMAN SPLICE SITES SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE SPLICE; SPLICEOSOME; INFORMATION THEORY; EVOLUTION; HUMAN ID PRE-MESSENGER-RNA; DNA-BINDING SITES; TRANSCRIPTION INITIATION SITES; HUMAN GENOME PROJECT; REGULATORY PROTEINS; ESCHERICHIA-COLI; ENERGY-DISSIPATION; JUNCTION SEQUENCES; MOLECULAR MACHINES; INTRON SEQUENCES C1 NCI, FREDERICK CANC RES & DEV CTR, MATH BIOL LAB, POB B, FREDERICK, MD 21702 USA. LINGANORE HIGH SCH, FREDERICK, MD 21701 USA. OI Schneider, Thomas/0000-0002-9841-1531 NR 98 TC 212 Z9 214 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 20 PY 1992 VL 228 IS 4 BP 1124 EP 1136 DI 10.1016/0022-2836(92)90320-J PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KE602 UT WOS:A1992KE60200011 PM 1474582 ER PT J AU BISSERBE, JC PASCAL, O DECKERT, J MAZIERE, B AF BISSERBE, JC PASCAL, O DECKERT, J MAZIERE, B TI POTENTIAL USE OF DPCPX AS PROBE FOR INVIVO LOCALIZATION OF BRAIN-A1 ADENOSINE RECEPTORS SO BRAIN RESEARCH LA English DT Article DE DPCPX; ADENOSINE-A1 RECEPTOR; EXVIVO AUTORADIOGRAPHY; RAT ID AUTORADIOGRAPHIC LOCALIZATION; UPTAKE SITES; ALZHEIMERS-DISEASE; PANIC DISORDERS; ANTAGONIST; CAFFEINE; ADENOSINE-A1-RECEPTORS; VISUALIZATION; HIPPOCAMPUS AB The suitability of (H-3)DPCPX (8-cyclopentyl-1,3-dipropylxanthine), a xanthine derivative, as an vivo probe for labelling adenosine A1 receptors was studied in rats. [H-3]DPCPX (nM) penetrated largely into the brain (0.8% of the injected dose per gram of brain tissue 5 min after injection). Brain concentrations stayed at a plateau level from 5 to 15 min after the injection. The distribution in the different brain regions was heterogeneous with the highest amount of [H-3]DPCPX in cerebellum and hippocampus and the lowest concentrations in hypothalamus and brain stem. Displacement (45-70% of total radioactivity) was obtained by the injection of 250 nM of cold DPCPX or cyclopentylxanthine, an analog of DPCPX. The ex vivo autoradiographic distribution of [H-3]DPCPX was similar to the in vitro autoradiographic distribution of tritiated A1 adenosine receptor ligand as [H-3]CHA. These results suggest the potential use of DPCPX for further in vivo investigation of A1 adenosine receptors with techniques such as positron emission tomography. C1 NIH,NEUROCHEM UNIT,BETHESDA,MD 20892. INSERM,SERV HOSP FREDERIC JOLIOT,ORSAY,FRANCE. NR 37 TC 21 Z9 22 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 DEC 18 PY 1992 VL 599 IS 1 BP 6 EP 12 DI 10.1016/0006-8993(92)90845-Z PG 7 WC Neurosciences SC Neurosciences & Neurology GA KF969 UT WOS:A1992KF96900002 PM 1493550 ER PT J AU ARTHUR, LO BESS, JW SOWDER, RC BENVENISTE, RE MANN, DL CHERMANN, JC HENDERSON, LE AF ARTHUR, LO BESS, JW SOWDER, RC BENVENISTE, RE MANN, DL CHERMANN, JC HENDERSON, LE TI CELLULAR PROTEINS BOUND TO IMMUNODEFICIENCY VIRUSES - IMPLICATIONS FOR PATHOGENESIS AND VACCINES SO SCIENCE LA English DT Article ID T4 MOLECULE; CELLS; ANTIGENS; MHC; BETA-2-MICROGLOBULIN; RECEPTOR; COMPLEX; HIV; HISTOCOMPATIBILITY; ASSOCIATION AB Cellular proteins associated with immunodeficiency viruses were identified by determination of the amino acid sequence of the proteins and peptides present in sucrose density gradient-purified human immunodeficiency virus (HIV)-1, HIV-2, and simian immunodeficiency virus (SIV). Beta2 microglobulin (beta2m) and the alpha and beta chains of human lymphocyte antigen (HLA) DR were present in virus preparations at one-fifth the concentration of Gag on a molar basis. Antisera to HLA DR, beta2m, as well as HLA class I precipitated intact viral particles, suggesting that these cellular proteins were physically associated with the surface of the virus. Antisera to class I, beta2m, and HLA DR also inhibited infection of cultured cells by both HIV-1 and SIV. The specific, selective association of these cellular proteins in a physiologically relevant manner has major implications for our understanding of the infection process and the pathogenesis of immunodeficiency viruses and should be considered in the design of vaccines. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. INSERM,UNITE RECH RETROVIRUS & MALAD ASSOCIEES,F-13273 MARSEILLE 9,FRANCE. RP ARTHUR, LO (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702, USA. RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01-CO-74102] NR 32 TC 478 Z9 484 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 18 PY 1992 VL 258 IS 5090 BP 1935 EP 1938 DI 10.1126/science.1470916 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KD088 UT WOS:A1992KD08800031 PM 1470916 ER PT J AU BLAESE, RM CULVER, KW ISHII, H OLDFIELD, EH RAM, Z WALLBRIDGE, S AF BLAESE, RM CULVER, KW ISHII, H OLDFIELD, EH RAM, Z WALLBRIDGE, S TI BRAIN-TUMOR TREATMENT - SIGNIFICANT CONTRIBUTIONS SO SCIENCE LA English DT Letter ID GLIOMA-CELLS; GENE C1 NINCDS,BETHESDA,MD 20892. RP BLAESE, RM (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 3 Z9 3 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 18 PY 1992 VL 258 IS 5090 BP 1960 EP 1960 DI 10.1126/science.1470923 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KD088 UT WOS:A1992KD08800040 PM 1470923 ER PT J AU NAGEY, DA BLACKMAN, JA WRIGHT, JN AF NAGEY, DA BLACKMAN, JA WRIGHT, JN TI THE GENERAL MEDICAL RECORD - CONCEPTS AND SUGGESTIONS FOR IMPLEMENTATION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. UNIV MARYLAND,DEPT MATH & STAT,CATONSVILLE,MD 21228. RP NAGEY, DA (reprint author), UNIV MARYLAND,SCH MED,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,22 S GREENE ST,BALTIMORE,MD 21201, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 17 PY 1992 VL 670 BP 109 EP 115 DI 10.1111/j.1749-6632.1992.tb26080.x PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KJ583 UT WOS:A1992KJ58300012 PM 1309078 ER PT J AU MUNSON, PJ TAYLOR, RC MICHAELS, GS AF MUNSON, PJ TAYLOR, RC MICHAELS, GS TI DNA CORRELATIONS SO NATURE LA English DT Letter RP MUNSON, PJ (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 5 TC 41 Z9 41 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 17 PY 1992 VL 360 IS 6405 BP 636 EP 636 DI 10.1038/360636a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KD082 UT WOS:A1992KD08200038 PM 1465126 ER PT J AU JONES, EA BERGASA, NV AF JONES, EA BERGASA, NV TI THE PRURITUS OF CHOLESTASIS AND THE OPIOID SYSTEM SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID VISUAL ANALOG SCORE; ORAL NALMEFENE; APPRAISAL RP JONES, EA (reprint author), NIDDKD,DIGEST DIS BRANCH,LIVER UNIT,LIVER DIS SECT,BLDG 10,ROOM 4D-52,BETHESDA,MD 20892, USA. NR 22 TC 58 Z9 59 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 16 PY 1992 VL 268 IS 23 BP 3359 EP 3362 DI 10.1001/jama.268.23.3359 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA KB732 UT WOS:A1992KB73200030 PM 1333541 ER PT J AU ORTALDO, JR GLENN, GM YOUNG, HA FREY, JL AF ORTALDO, JR GLENN, GM YOUNG, HA FREY, JL TI NATURAL-KILLER (NK) CELL LYTIC DYSFUNCTION AND PUTATIVE NK CELL-RECEPTOR EXPRESSION ABNORMALITY IN MEMBERS OF A FAMILY WITH CHROMOSOME 3P-LINKED VONHIPPEL-LINDAU DISEASE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LYMPHOCYTES; LOCUS AB Background. Using antibodies to a putative natural killer (NK) cell receptor (pNKR), we recently cloned a novel cDNA and localized this gene to the short arm of human chromosome 3, region 3p21-3p24. Individuals susceptible to or clinically manifesting von Hippel-Lindau disease (VHL) have a genetic defect telomeric to this region on chromosome 3. This defect, resulting in VHL, is manifested by a high incidence of certain tumors. Purpose: Based on the location of this gene, we sought to determine if VHL patients have a defect in gene expression of pNKR. Methods: Because of the proximity of the VHL and pNKR genetic regions, the variable expression of VHL tumors, and the ability of NK cells to target tumor cells, we investigated NK cell activity and other aspects of the immunologic status in 40 members (four branches) of a family with a high incidence of VHL tumors. Results: Individuals affected with VHL and lacking in normal surface expression of pNKR had virtually no NK cell lytic activity. Analysis of genotypes and phenotypes of all subjects revealed that the greatest difference in NK cell lytic activity (P = .0002) was seen when family members exhibited both VHL and pNKR surface expression defects, compared with normal relatives who had neither defect. Furthermore, the lack of NK cell activity strongly correlated (P = .0005) with abnormal pNKR protein surface expression. Of particular interest, individuals who lacked NK cell activity had normal numbers of NK cells. In addition, analysis of leukocyte subsets indicated normal numbers of T and B cells, monocytes, and NK cells in both affected and normal individuals. Conclusions: These data indicate that although all affected individuals have the cell population responsible for NK cell activity, many have cells low in expression of pNKR and lack functional NK cell activity. Overall, these results indicate that, in addition to a predisposition to the development of neoplasms, VHL patients have a defect in a specific mechanism of natural immunosurveillance that correlates with a defect in expression of a novel large granular lymphocyte pNKR protein. C1 NCI,DIV CANC BIOL DIAGNOSIS & CTR,CANC DIAGNOSIS BRANCH,BETHESDA,MD 20892. RP ORTALDO, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA. NR 17 TC 8 Z9 8 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 16 PY 1992 VL 84 IS 24 BP 1897 EP 1903 DI 10.1093/jnci/84.24.1897 PG 7 WC Oncology SC Oncology GA KB984 UT WOS:A1992KB98400013 PM 1460671 ER PT J AU FRIEDMAN, HS DOLAN, ME MOSCHEL, RC PEGG, AE FELKER, GM RICH, J BIGNER, DD SCHOLD, SC AF FRIEDMAN, HS DOLAN, ME MOSCHEL, RC PEGG, AE FELKER, GM RICH, J BIGNER, DD SCHOLD, SC TI ENHANCEMENT OF NITROSOUREA ACTIVITY IN MEDULLOBLASTOMA AND GLIOBLASTOMA-MULTIFORME SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; COLON TUMOR-CELLS; ALKYLATING-AGENTS; CYTO-TOXICITY; BRAIN-TUMORS; SENSITIVITY; DNA; REPAIR; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; O6-METHYLGUANINE AB Background: Although chemotherapy offers promise of increased survival for children with medulloblastoma and glioblastoma multiforme, drug resistance occurs frequently, resulting in tumor progression and death. Resistance to nitrosoureas and methylating agents, which damage DNA, can be mediated by a DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGAT). Depletion of this protein with alkylguanines or methylating agents, however, restores tumor cell sensitivity to the cytotoxicity of chloroethylnitrosoureas (e.g., carmustine [BCNU]). Purpose: This study was designed to determine whether resistance to the activity of nitrosourea (the drug BCNU) in BCNU-resistant human medulloblastoma (D341 Med) and human glioblastoma multiforme (D-456 MG) can be reversed by the methylating agent streptozocin and the O6-substituted guanines O6-methylguanine and O6-benzylguanine. Methods: Xenografts were grown subcutaneously in athymic BALB/c mice. BCNU was administered as a single intraperitoneal injection at doses of 100 mg/m2, 75 mg/m2, or 38 mg/m2-i.e., 1.0, 0.75, or 0.38, respectively, of the dose lethal to 10% of treated animals (LD10). Mice were treated intraperitoneally with a single dose of O6-benzylguanine or O6-methylguanine (240 mg/m2) or with streptozocin (600 mg/m2) daily for 4 days. Response was assessed by tumor growth delay and tumor regression. AGAT activity in the xenografts was measured at 1 and 6 hours after pretreatment, at the time tumors were excised. Results: Pretreatment with O6-benzylguanine, O6-methylguanine, or streptozocin reduced AGAT activity to 4%, 25%, and 95% of control values, respectively, in D341 Med and 0%, 0%, and 25% of control values, respectively, in D-456 MG 1 hour after injection. After 6 hours, levels changed to 7%, 61%, and 116% of control values in D341 Med and 0%, 79%, and 21% of control values in D-456 MG, respectively. Both D341 Med and D-456 MG xenografts were completely resistant to BCNU at its LD10. Pretreatment with O6-benzylguanine increased BCNU sensitivity in both types of xenograft. In contrast, treatment with BCNU plus O6-methylguanine or streptozocin did not produce growth delays substantially different from those produced by BCNU alone, reflecting the more efficient depletion of AGAT by O6-benzylguanine. Following therapy with BCNU plus O6-benzylguanine at 0.38 LD10, tumor regressions were seen in eight of 10 D341 Med and in all 10 D-456 MG xenografts. Conclusion: We recommend comprehensive clinical toxicologic evaluation of combination therapy with O6-benzylguanine plus BCNU, which would allow subsequent design of phase I clinical trials. C1 DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,PREUSS LAB BRAIN TUMOR RES,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,CHICAGO,IL 60637. NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21701. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PHARMACOL,HERSHEY,PA 17033. FU NCI NIH HHS [CA-18137, CA-11898, CA-44640] NR 29 TC 122 Z9 124 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 16 PY 1992 VL 84 IS 24 BP 1926 EP 1931 DI 10.1093/jnci/84.24.1926 PG 6 WC Oncology SC Oncology GA KB984 UT WOS:A1992KB98400018 PM 1334154 ER PT J AU SOTOS, GA LIEBMANN, JE KOHLER, DR LONGO, DL AF SOTOS, GA LIEBMANN, JE KOHLER, DR LONGO, DL TI REACTIVATION OF THERMAL BURN BY METHOTREXATE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,PHARM SERV SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. RP SOTOS, GA (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 16 PY 1992 VL 84 IS 24 BP 1936 EP 1938 DI 10.1093/jnci/84.24.1936 PG 3 WC Oncology SC Oncology GA KB984 UT WOS:A1992KB98400020 PM 1460675 ER PT J AU FEUER, EJ WUN, LM AF FEUER, EJ WUN, LM TI HOW MUCH OF THE RECENT RISE IN BREAST-CANCER INCIDENCE CAN BE EXPLAINED BY INCREASES IN MAMMOGRAPHY UTILIZATION - A DYNAMIC POPULATION-MODEL APPROACH SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE BREAST NEOPLASMS; INCIDENCE; MAMMOGRAPHY; MASS SCREENING; POPULATION DYNAMICS; POPULATION SURVEILLANCE ID DETECTION DEMONSTRATION PROJECT; UNITED-STATES; SCREENING PROGRAMS; TRENDS; CONNECTICUT; MORTALITY; DISEASE; WOMEN AB Largely unexplained increases in breast cancer incidence of about 1% per year have been documented back to the 1940s. Since 1982, breast cancer incidence in women aged 40 years and above has been increasing at a faster rate than this long-term secular trend, especially in women aged 60 years and above. Increases in the use of mammography since 1982 (which have been documented in population surveys of women) provide the most plausible explanation for the incidence increase over the long-term secular trend. A study by White et al. (J Natl Cancer Inst 1990;82:1546-52) found that, for women aged 45-64 years, the increase in mammography utilization could explain the incidence increase, while for women aged 65-74 years, it could account for only half the increase. The authors have developed an alternative model to that of White et al. that incorporates estimates of differential lead time (time from screen detection to clinical detection in the absence of screening) by age group. Using this model, the authors show that if older women have longer lead times, then similar increases in mammography utilization across age groups will lead to a larger incidence increase in older women. Thus, the observed increases in mammography utilization are generally concordant with increases in incidence, even in the older age groups. RP FEUER, EJ (reprint author), NCI,DIV CANC,PREVENT & CONTROL,EPN 313,9000 ROCKVILLE,BETHESDA,MD 20892, USA. NR 40 TC 98 Z9 99 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 1992 VL 136 IS 12 BP 1423 EP 1436 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KL891 UT WOS:A1992KL89100001 PM 1288272 ER PT J AU BIKKINA, M LARSON, MG LEVY, D AF BIKKINA, M LARSON, MG LEVY, D TI PROGNOSTIC IMPLICATIONS OF ASYMPTOMATIC VENTRICULAR ARRHYTHMIAS - THE FRAMINGHAM HEART-STUDY SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE EXTRASYSTOLE; CORONARY DISEASE; ARRHYTHMIA; MYOCARDIAL INFARCTION ID ACUTE MYOCARDIAL-INFARCTION; SUDDEN-DEATH; HEALTHY-SUBJECTS; DISEASE; HYPERTROPHY; FREQUENT; COMPLEX; ECTOPY; RISK; MASS AB Objective: To evaluate the prevalence and prognostic significance of asymptomatic complex or frequent ventricular premature beats detected during ambulatory electrocardiographic (ECG) monitoring. Design: Cohort study with a follow-up period of 4 to 6 years. Setting: Population-based. Participants: Surviving patients of the original Framingham Heart Study cohort and offspring of original cohort members (2727 men and 3306 women). Measurements: One-hour ambulatory electrocardiography. Results: The age-adjusted prevalence of complex or frequent arrhythmia (more than 30 ventricular premature complexes per hour or multiform premature complexes, ventricular couplets, ventricular tachycardia, or R-on-T ventricular premature complexes) was 12% (95% Cl, 11% to 13%) in the 2425 men without clinically evident coronary heart disease and 33% (Cl, 24% to 42%) in the 302 men with coronary heart disease. The corresponding values in women (3064 without disease and 242 with disease) were 12% (Cl, 11 % to 13%) and 26% (Cl, 9% to 43%). After adjusting for age and traditional risk factors for coronary heart disease in a Cox proportional hazards model, men without coronary heart disease who had complex or frequent ventricular arrhythmias were at increased risk for both all-cause mortality (relative risk, 2.30; Cl, 1.65 to 3.20) and the occurrence of myocardial infarction or death from coronary heart disease (relative risk, 2.12; Cl, 1.33 to 3.38). In men with coronary heart disease and in women with and without coronary heart disease, complex or frequent arrhythmias were not associated with an increased risk for either outcome. Conclusions: In men who do not have clinically apparent coronary heart disease, the incidental detection of ventricular arrhythmias is associated with a twofold increase in the risk for all-cause mortality and myocardial infarction or death due to coronary heart disease. The preventive and therapeutic implications of these findings await further investigation. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY, 5 THURBER ST, FRAMINGHAM, MA 01701 USA. NHLBI, BETHESDA, MD 20892 USA. BOSTON UNIV, SCH MED, BOSTON, MA 02118 USA. BETH ISRAEL HOSP, BOSTON, MA 02215 USA. NR 51 TC 109 Z9 113 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 15 PY 1992 VL 117 IS 12 BP 990 EP 996 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KB980 UT WOS:A1992KB98000003 PM 1280018 ER PT J AU GUY, J DHANIREDDY, R MUKHERJEE, AB AF GUY, J DHANIREDDY, R MUKHERJEE, AB TI SURFACTANT-PRODUCING RABBIT PULMONARY ALVEOLAR TYPE-II CELLS SYNTHESIZE AND SECRETE AN ANTIINFLAMMATORY PROTEIN, UTEROGLOBIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HYALINE-MEMBRANE DISEASE; PHOSPHOLIPASE-A2; TRANSGLUTAMINASE; CLEAVAGE; INFANTS; GENE; LUNG C1 GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. NICHHD,HUMAN GENET BRANCH,DEV GENET SECT,BETHESDA,MD 20892. RI Dhanireddy, Ramasubbareddy/I-3699-2016 OI Dhanireddy, Ramasubbareddy/0000-0002-8787-6499 NR 35 TC 27 Z9 29 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 DEC 15 PY 1992 VL 189 IS 2 BP 662 EP 669 DI 10.1016/0006-291X(92)92252-S PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KD219 UT WOS:A1992KD21900010 PM 1472037 ER PT J AU LINK, E EDELMANN, L CHOU, JH BINZ, T YAMASAKI, S EISEL, U BAUMERT, M SUDHOF, TC NIEMANN, H JAHN, R AF LINK, E EDELMANN, L CHOU, JH BINZ, T YAMASAKI, S EISEL, U BAUMERT, M SUDHOF, TC NIEMANN, H JAHN, R TI TETANUS TOXIN ACTION - INHIBITION OF NEUROTRANSMITTER RELEASE LINKED TO SYNAPTOBREVIN PROTEOLYSIS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SYNAPTIC VESICLES; MEMBRANE-PROTEIN; ENDOCRINE-CELLS; EXOCYTOSIS; BINDING C1 YALE UNIV,SCH MED,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510. BUNDESFORSCH SANSTALT VIRUSKRANKHEITEN TIERE,W-7400 TUBINGEN,GERMANY. NIMH,LCB,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,HOWARD HUGHES MED INST,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT MOLEC GENET,DALLAS,TX 75235. RP LINK, E (reprint author), YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06510, USA. OI Eisel, Ulrich/0000-0003-4178-0384 NR 29 TC 231 Z9 235 U1 0 U2 7 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 DEC 15 PY 1992 VL 189 IS 2 BP 1017 EP 1023 DI 10.1016/0006-291X(92)92305-H PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KD219 UT WOS:A1992KD21900063 PM 1361727 ER PT J AU OOI, GT TSENG, LYH RECHLER, MM AF OOI, GT TSENG, LYH RECHLER, MM TI POSTTRANSCRIPTIONAL REGULATION OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-2 MESSENGER-RNA IN DIABETIC RAT-LIVER SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TISSUE DISTRIBUTION; HEPATOMA-CELLS; IGF-I; EXPRESSION; HORMONE RP OOI, GT (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BLDG 10,ROOM 8D14,BETHESDA,MD 20892, USA. NR 26 TC 22 Z9 22 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 DEC 15 PY 1992 VL 189 IS 2 BP 1031 EP 1037 DI 10.1016/0006-291X(92)92307-J PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KD219 UT WOS:A1992KD21900065 PM 1281986 ER PT J AU BODENNER, DL MCCLASKEY, JH KIM, MK MIXSON, AJ WEINTRAUB, BD AF BODENNER, DL MCCLASKEY, JH KIM, MK MIXSON, AJ WEINTRAUB, BD TI THE PROTOONCOGENES C-FOS AND C-JUN MODULATE THYROID-HORMONE INHIBITION OF HUMAN THYROTROPIN-BETA SUBUNIT GENE-EXPRESSION IN OPPOSITE DIRECTIONS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AP1 BINDING-SITE; DNA-BINDING; GLUCOCORTICOID RECEPTOR; NEGATIVE REGULATION; RETINOIC ACID; TRANSCRIPTION; PROMOTER; ELEMENT; COMPLEXES; INDUCTION RP BODENNER, DL (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 5 Z9 5 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 DEC 15 PY 1992 VL 189 IS 2 BP 1050 EP 1056 DI 10.1016/0006-291X(92)92310-T PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KD219 UT WOS:A1992KD21900068 PM 1335239 ER PT J AU DEMITRACK, MA GOLD, PW DALE, JK KRAHN, DD KLING, MA STRAUS, SE AF DEMITRACK, MA GOLD, PW DALE, JK KRAHN, DD KLING, MA STRAUS, SE TI PLASMA AND CEREBROSPINAL-FLUID MONOAMINE METABOLISM IN PATIENTS WITH CHRONIC FATIGUE SYNDROME - PRELIMINARY FINDINGS SO BIOLOGICAL PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; BARR VIRUS-INFECTION; RESISTANT DEPRESSED-PATIENTS; IMMUNOLOGICAL ABNORMALITIES; SEROTONIN RELEASE; NOREPINEPHRINE; PERSISTENT; ILLNESS; INVITRO; CELLS AB The syndrome of chronic fatigue, feverishness, diffuse pains, and other constitutional complaints, often precipitated by an acute infectious illness and aggravated by physical and emotional stressors, has a lengthy history in the medical literature. The Centers for Disease Control (CDC) recently formulated a case definition, renaming the illness ''chronic fatigue syndrome.'' Nevertheless, there remain few biological data that can validate the existence of this syndrome as distinct from a wide variety of other, largely psychiatric disorders, and little understanding of its pathogenesis. In the present study, basal plasma and cerebrospinal fluid levels of the monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were determined in 19 patients meeting CDC research case criteria for chronic fatigue syndrome and in 17 normal individuals. Patients with chronic fatigue syndrome showed a significant reduction in basal plasma levels of MHPG and a significant increase in basal plasma levels of 5-HIAA. Although the functional significance of these findings has not been definitively elucidated, they are compatible with the clinical presentation of a syndrome associated with chronic lethargy and fatigue, and with evidence of persistent immune stimulation, and lend support to the idea that chronic fatigue syndrome represents a clinical entity with potential biological specificity. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP DEMITRACK, MA (reprint author), UNIV MICHIGAN,MED CTR,DEPT PSYCHIAT,1500 E MED CTR DR,ANN ARBOR,MI 48109, USA. RI Kling, Mitchel/F-4152-2010; Demitrack, Mark/I-7697-2013 OI Kling, Mitchel/0000-0002-2232-1409; NR 64 TC 55 Z9 55 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1992 VL 32 IS 12 BP 1065 EP 1077 DI 10.1016/0006-3223(92)90187-5 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KG100 UT WOS:A1992KG10000002 PM 1282370 ER PT J AU SCHACTER, LP ROZENCWEIG, M BELTANGADY, M ALLAN, JD CANETTA, R COOLEY, TP DOLIN, R KELLEY, S LAMBERT, J LIEBMAN, HA MESSINA, M NICAISE, C SEIDLIN, M VALENTINE, FT YARCHOAN, R SMALDONE, LF AF SCHACTER, LP ROZENCWEIG, M BELTANGADY, M ALLAN, JD CANETTA, R COOLEY, TP DOLIN, R KELLEY, S LAMBERT, J LIEBMAN, HA MESSINA, M NICAISE, C SEIDLIN, M VALENTINE, FT YARCHOAN, R SMALDONE, LF TI EFFECTS OF THERAPY WITH DIDANOSINE ON HEMATOLOGIC PARAMETERS IN PATIENTS WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE SO BLOOD LA English DT Article ID AIDS-RELATED COMPLEX; PHASE-I TRIAL; 2',3'-DIDEOXYINOSINE DDI; TOXICITY; ABNORMALITIES; 2',3'-DIDEOXYNUCLEOSIDES; INFECTIVITY; INHIBITION; INVITRO; PROFILE C1 ROCHESTER MED CTR,ROCHESTER,NY. BOSTON CITY HOSP,BOSTON,MA 02118. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. BELLEVUE HOSP CTR,NEW YORK,NY 10016. NIH,BETHESDA,MD 20892. RP SCHACTER, LP (reprint author), BRISTOL MYERS SQUIBB,5 RES PKWY,POB 5100,WALLINGFORD,CT 06492, USA. NR 20 TC 25 Z9 25 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1992 VL 80 IS 12 BP 2969 EP 2976 PG 8 WC Hematology SC Hematology GA KC838 UT WOS:A1992KC83800003 PM 1467512 ER PT J AU PETRYLAK, DP SCHER, HI LI, ZH MYERS, CE GELLER, NL AF PETRYLAK, DP SCHER, HI LI, ZH MYERS, CE GELLER, NL TI PROGNOSTIC FACTORS FOR SURVIVAL OF PATIENTS WITH BIDIMENSIONALLY MEASURABLE METASTATIC HORMONE-REFRACTORY PROSTATIC-CANCER TREATED WITH SINGLE-AGENT CHEMOTHERAPY SO CANCER LA English DT Article DE PROSTATE CANCER; PROGNOSTIC FACTORS; HORMONE REFRACTORY; MEASURABLE; SURVIVAL ID PHASE-II TRIAL; ACID-PHOSPHATASE; ANTIGEN; ADENOCARCINOMA; CARCINOMA; DISEASE; MARKER AB Background. A range of response proportions have been reported using the same single-agent inpatients with hormone refractory prostatic cancer. To assess whether these results were due to imbalances in prognostic factors, the authors evaluated a series of prognostic factors for survival in patients with prostatic cancer treated with chemotherapy. Methods. Complete data sets were available in 146 patients, in whom 27 individual variables were considered in univariate analysis. Significant factors (P < 0.05) were then evaluated using regression analysis along with transformations of the data to obtain a Cox and exponential model. The derived model was then evaluated on an independent data set from the National Cancer Institute treated with suramin. Results. In univariate analysis in order of significance, the serum alkaline phosphate (0.0018), serum lactic dehydrogenase (0.006), prior radiation therapy (0.007), serum aspartate amino transferase (0.02), presence of liver disease (0.033), and pretreatment Karnofsky performance status (0.04) were associated with survival. In the regression analysis, only the log-transformed lactic dehydrogenase (LDH) and normal versus abnormal alkaline phosphatase were significant. This model was confirmed with an independent data set from patients treated with the putative growth factor inhibitor suramin. Conclusions. This analysis emphasizes important factors that can be used to stratify patients in future phase II and III trials. C1 MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,GENITOURINARY ONCOL SERV,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT EPIDEMIOL & BIOSTAT,DIV BIOSTAT,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,COLL MED,DEPT MED,NEW YORK,NY 10021. NIH,MED BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-05826, CM-57732, CA-09207-14] NR 31 TC 32 Z9 34 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1992 VL 70 IS 12 BP 2870 EP 2878 PG 9 WC Oncology SC Oncology GA KB640 UT WOS:A1992KB64000022 PM 1451069 ER PT J AU FRIEDMAN, E DEMARCO, L GEJMAN, PV NORTON, JA BALE, AE AURBACH, GD SPIEGEL, AM MARX, SJ AF FRIEDMAN, E DEMARCO, L GEJMAN, PV NORTON, JA BALE, AE AURBACH, GD SPIEGEL, AM MARX, SJ TI ALLELIC LOSS FROM CHROMOSOME-11 IN PARATHYROID TUMORS SO CANCER RESEARCH LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; DINUCLEOTIDE REPEAT POLYMORPHISM; SMALL REGION; TYPE-1; GENE; LINKAGE; CANCER; HETEROZYGOSITY; RETINOBLASTOMA; LOCALIZATION AB Parathyroid tumors may occur in a sporadic fashion or, more rarely, as part of a familial syndrome (such as familial multiple endocrine neoplasia type I). The MENI gene has been mapped by linkage analysis to chromosome 11 at band q11-q13, and presumably acts as a tumor suppressor gene. In the present study, which is an extension of our previous studies, we examined 41 parathyroid tumors from patients with familial multiple endocrine neoplasia type I and 61 sporadic parathyroid tumors with markers on chromosome 11, to assess the extent of allelic loss in those tumors. Twenty-four of the MENI-associated tumors (58%) and 16 of the sporadic parathyroid tumors (26%) displayed allelic loss from chromosome 11. The region of overlap of the allelic losses in the MENI-associated tumors enables us to place the MENI gene between PGA centromerically and INT2 telomerically, a region spanning about 7.5 cM. Taken together with locus ordering by linkage analysis, this clearly localizes the MENI gene telomeric to the PGA locus. Our inability to detect allelic loss on chromosome 11 in some parathyroid tumors suggests the existence of other genes involved in the development and/or progression of this subgroup of presumably monoclonal tumors; or that localized events involving the 11q tumor suppressor gene have occurred in some parathyroid tumors whose detection is beyond the sensitivity of our analysis; or that at least some of the specimens analyzed were in fact primarily hyperplastic parathyroid tissue. C1 NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. RI De Marco, Luiz /H-6275-2012 NR 37 TC 100 Z9 100 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1992 VL 52 IS 24 BP 6804 EP 6809 PG 6 WC Oncology SC Oncology GA KB979 UT WOS:A1992KB97900011 PM 1360870 ER PT J AU WASSERMANN, K PIRSEL, M BOHR, VA AF WASSERMANN, K PIRSEL, M BOHR, VA TI OVEREXPRESSION OF METALLOTHIONEIN IN CHINESE-HAMSTER OVARY CELLS AND ITS EFFECT ON NITROGEN MUSTARD-INDUCED CYTOTOXICITY - ROLE OF GENE-SPECIFIC DAMAGE AND REPAIR SO CANCER RESEARCH LA English DT Article ID DIHYDROFOLATE-REDUCTASE GENE; PREFERENTIAL DNA-REPAIR; II GENES; ALKYLATING-AGENTS; L1210 CELLS; CHO CELLS; RESISTANCE; ACTIVATION; EXPRESSION; INDUCTION AB Overexpression of metallothionein in mammalian cells has been associated with protection from cytotoxic chemicals and acquired resistance of tumors to cytotoxic drugs. The mechanism of this effect, however, remains unclear. We have explored whether cytotoxicity of the bifunctional alkylating agent nitrogen mustard was correlated with the extent of DNA damage formation and repair in the metallothionein gene regions in Chinese hamster ovary cells. The DNA damage and repair were examined in metallothionein-overexpressing, cadmium-resistant Chinese hamster ovary cells, Cd(r)200T1, with or without zinc-induced transcriptional activation, and in the parental CHO-met- cell line. The zinc-induced Cd(r)200T1 cells tolerated significantly higher doses of nitrogen mustard than did the uninduced Cd(r)200T1 variant. The parental CHO-met cells, which did not have any detectable metallothionein expression, were even more resistant to nitrogen mustard than the zinc-induced Cd(r) variants. Nitrogen mustard-induced N-alkylpurines were formed with a higher frequency in inactive genomic regions than in the active genes. The removal of N-alkylpurines was similar in the active MT I gene region in Cd(r)200T1 and the silent MT I gene region in the parental cells, and the expression of these genes was determined bv Northern assay. The MT II gene-containing region was repaired less efficiently than the MT I gene, independently of zinc induction. Further, preferential repair of nitrogen mustard-induced N-alkylpurines were detected in a single copy of the essential active dihydrofolate reductase gene as compared to a downstream noncoding region. This preferential repair was unaffected by the presence of zinc. Neither damage formation nor repair kinetics in the MT gene regions seemed to parallel the observed spectrum of sensitivity to HN2. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI Pirsel, Miroslav/A-9996-2008 NR 43 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1992 VL 52 IS 24 BP 6853 EP 6859 PG 7 WC Oncology SC Oncology GA KB979 UT WOS:A1992KB97900019 PM 1458473 ER PT J AU JOHNSTON, PG RONDINONE, CM VOELLER, D ALLEGRA, CJ AF JOHNSTON, PG RONDINONE, CM VOELLER, D ALLEGRA, CJ TI IDENTIFICATION OF A PROTEIN FACTOR SECRETED BY 3T3-L1 PREADIPOCYTES INHIBITORY FOR THE HUMAN MCF-7 BREAST-CANCER CELL-LINE SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; TRANSFORMING GROWTH-FACTOR; FACTOR-BETA; MOUSE; CULTURE; FIBROBLASTS; EXPRESSION; CARCINOMA; GLAND; MORPHOGENESIS AB The 3T3-L1 cell line is a preadipocyte cell line derived from the Swiss 3T3 mouse fibroblast cell line. We have compared the effect of 3T3-L1 conditioned medium (3T3-L1 CM) and Swiss 3T3 conditioned medium (3T3 CM) on the growth of normal mouse mammary cells (NMMG) and the human MCF-7 breast carcinoma cell line. 3T3 CM increased the growth of both NMMG and MCF-7 cells by 19 +/- 2% (SD) and 24 +/- 3%, respectively, and increased thymidine incorporation by 74 +/- 4% and 104 +/- 8%, respectively. Conditioned medium from 3T3-L1 cells stimulated the growth of NMMG cells by 64 +/- 2%; in contrast, 3T3-L1 CM inhibited the growth of MCF-7 cells by 36 +/- 1%. In parallel with these growth studies, thymidine incorporation increased by 20 +/- 4% in NMMG cells and decreased by 72 +/- 5% in the MCF-7 cells. Moreover, a similar effect was also noted in NCI H630 colon cancer cells, where 3T3-L1 CM produced a 58 +/- 4% decrease in growth and a 82 +/- 6% decrease in thymidine incorporation. Heating the 3T3-L1 CM at 100-degrees-C for 30 min destroyed all inhibitory activity. Several known inhibitory growth factors (fibroblast growth factor, 20 ng/ml; interleukin 6, 1000 units/ml; tumor necrosis factor alpha, 15 ng/ml; transforming growth factor beta, 1 ng/ml) were tested for activity in the MCF-7 cells. Tumor necrosis factor alpha and transforming growth factor beta produced a 97% and 67% inhibition of thymidine uptake, respectively, whereas interleukin 6 and fibroblast growth factor had no effect. Neither transforming growth factor beta nor tumor necrosis factor alpha activity was detectable in 3T3-L1 CM using an enzyme-linked immunosorbent assay. High-performance liquid chromatography fractionation of the 3T3-L1 CM revealed that the inhibitory activity eluted at a molecular weight of 67,000; moreover, silver staining of these eluates on a denaturing polyacrylamide gel revealed that M(r) 69,000 peptide was the predominant protein band in the inhibitory fractions. Thus 3T3-L1 CM stimulates the growth of normal breast epithelial cells and inhibits the growth of MCF-7 breast cancer cells. This inhibitory activity appears to be due to a protein secreted by 3T3-L1 preadipocytes. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. RP JOHNSTON, PG (reprint author), USN HOSP,NCI,DIV CANC TREATMENT,MED ONCOL BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20892, USA. NR 34 TC 23 Z9 24 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 DEC 15 PY 1992 VL 52 IS 24 BP 6860 EP 6865 PG 6 WC Oncology SC Oncology GA KB979 UT WOS:A1992KB97900020 PM 1458474 ER PT J AU REEVES, SA CHAVEZKAPPEL, C DAVIS, R ROSENBLUM, M ISRAEL, MA AF REEVES, SA CHAVEZKAPPEL, C DAVIS, R ROSENBLUM, M ISRAEL, MA TI DEVELOPMENTAL REGULATION OF ANNEXIN-II (LIPOCORTIN-2) IN HUMAN BRAIN AND EXPRESSION IN HIGH-GRADE GLIOMA SO CANCER RESEARCH LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; RADIAL GLIAL-CELLS; TYROSINE PHOSPHORYLATION; MESSENGER-RNA; RECEPTOR GENE; RHESUS-MONKEY; SUBSTRATE; KINASE; ASTROCYTES; CALPACTIN AB In experiments to identify molecules that might be important in the pathogenesis of glioblastoma multiforme, the most common malignant brain tumor, we found that annexin II (Lipocortin 2, p36), a likely second messenger in several different mitogenic pathways, was highly expressed in tumor tissue of glioblastoma multiforme (9 of 9) and highly anaplastic astrocytoma (2 of 6), but not in astrocytomas of lower pathological grade (0 of 6). We also detected high levels of annexin II expression in fetal brain during the period when radial glia proliferate, although annexin II expression was not detected in normal adult brain. These data demonstrate that annexin II expression is developmentally regulated in the human central nervous system and suggest that the early progenitor radial glia share important characteristics with highly malignant glial tumors. C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT PATHOL,SAN FRANCISCO,CA 94143. NCI,PEDIAT BRANCH,MOLEC GENET SECT,BETHESDA,MD 20892. RP REEVES, SA (reprint author), UNIV CALIF SAN FRANCISCO,SCH MED,DEPT NEUROL SURG,BRAIN TUMOR RES CTR,SAN FRANCISCO,CA 94143, USA. NR 34 TC 80 Z9 84 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1992 VL 52 IS 24 BP 6871 EP 6876 PG 6 WC Oncology SC Oncology GA KB979 UT WOS:A1992KB97900022 PM 1333884 ER PT J AU COWLEN, MS ELING, TE AF COWLEN, MS ELING, TE TI MODULATION OF C-JUN AND JUN-B MESSENGER-RNA AND INHIBITION OF DNA-SYNTHESIS BY PROSTAGLANDIN-E2 IN SYRIAN-HAMSTER EMBRYO CELLS SO CANCER RESEARCH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ARACHIDONIC-ACID METABOLISM; ENDOTHELIAL-CELLS; GENE; ONCOGENE; EXPRESSION; AP-1; FOS; CYCLOOXYGENASE; TRANSCRIPTION AB Fatty acid metabolites such as prostaglandins are important regulators of DNA synthesis and cell proliferation. However, the mechanisms involved in this regulation are unclear. We have examined the effects of several fatty acid metabolites on the expression of the growth-related genes c-jun and jun-B in Syrian hamster embryo cells. Treatment of cells with prostaglandin E2 (PGE2) resulted in the inhibition of epidermal growth factor (EGF)-induced DNA synthesis and c-jun mRNA accumulation, whereas PGE2 augmented EGF-stimulated jun-B mRNA and markedly stimulated jun-B accumulation in the absence of EGF. Treatment of cells with PGE2 resulted in rapid accumulation of cyclic AMP (cAMP), whereas prostaglandin F2alpha did not stimulate cAMP formation and did not alter EGF-stimulated DNA synthesis or accumulation of c-jun or jun-B mRNA. Forskolin and 8-(4-chlorophenylthio)cAMP mimicked the effects of PGE2 on DNA synthesis and on the expression of c-jun and jun-B, suggesting the involvement of cAMP. We have shown that EGF-induced DNA synthesis requires the formation of hydroxyoctadecadienoic acids, formed from linoleic acid by a 15-lipoxygenase, in Syrian hamster embryo cells (Glasgow et al., J. Biol. Chem., 267. 10771-10779). Inhibition of this 15-lipoxygenase blocked EGF-dependent hydroxyoctadecadienoic acid formation and mitogenesis but did not affect EGF-stimulated c-jun or jun-B mRNA accumulation. The data suggest that the modulation of EGF-dependent DNA synthesis by PGE2 is associated with altered expression of c-jun and jun-B in Syrian hamster embryo cells. In contrast, hydroxyoctadecadienoic acids appear to act downstream or divergent from c-jun and jun-B expression in the regulation of EGF-dependent DNA synthesis. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,MD 19-04,RES TRIANGLE PK,NC 27709. NR 32 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1992 VL 52 IS 24 BP 6912 EP 6916 PG 5 WC Oncology SC Oncology GA KB979 UT WOS:A1992KB97900028 PM 1333886 ER PT J AU KANTOR, J IRVINE, K ABRAMS, S SNOY, P OLSEN, R GREINER, J KAUFMAN, H EGGENSPERGER, D SCHLOM, J AF KANTOR, J IRVINE, K ABRAMS, S SNOY, P OLSEN, R GREINER, J KAUFMAN, H EGGENSPERGER, D SCHLOM, J TI IMMUNOGENICITY AND SAFETY OF A RECOMBINANT VACCINIA VIRUS-VACCINE EXPRESSING THE CARCINOEMBRYONIC ANTIGEN GENE IN A NONHUMAN PRIMATE SO CANCER RESEARCH LA English DT Article ID ACTIVE-SPECIFIC IMMUNOTHERAPY; COLORECTAL-CANCER; IMMUNE-COMPLEXES; TUMOR-CELLS; CEA; MELANOMA; CARCINOMA; ADJUVANT; ANTIBODIES; PRODUCT AB We have previously reported the development of a recombinant vaccinia virus vaccine expressing the human carcinoembryonic antigen (CEA) gene, designated rV(NYC)-CEA. This construct has been shown to elicit specific anti-CEA immune responses and an antitumor effect in a murine tumor model. In the studies reported here, the safety and immunogenicity of this recombinant vaccinia virus were evaluated in a rhesus monkey model. Human CEA is a M(r) 180,000 glycoprotein expressed in approximately 90% of gastrointestinal carcinomas and in some breast and non-small cell lung carcinomas. This family also includes normal cross-reacting antigen (NCA). Rhesus monkeys, like humans, have some NCA on the surface of their granulocytes. Eight monkeys were immunized 3 or 4 times by skin scarification with the recombinant CEA vaccine and four monkeys received wild-type vaccinia virus as control. After three vaccinations, all rV(NYC)-CEA-vaccinated animals exhibited a strong anti-CEA antibody response as measured by enzyme-linked immunosorbent assay. The functional ability of these antibodies to mediate lysis of a CEA-bearing tumor cell was demonstrated using human effector cells. This response could be enhanced by interleukin 2. Cellular immunity to CEA was measured by delayed-type hypersensitivity upon intradermal challenge with purified CEA. Only those animals receiving the recombinant vaccine displayed significant anti-CEA responses. Furthermore, peripheral blood mononuclear cells from immunized monkeys were found to proliferate in response to CEA stimulation. All vaccinated monkeys developed local skin irritation at the site of the vaccination, regional lymphadenopathy, and low-grade fevers after immunization. Following immunization with rV(NYC)-CEA, the response was consistent with the usual constitutional symptoms seen with human smallpox virus immunization. Blood counts, differentials, and hepatic and renal chemistries remained normal in all animals throughout the study and for up to 1 year following the primary vaccination. No evidence of immunological cross-reactivity to NCA was found by either a fall in the granulocyte count or analyses for anti-NCA antibodies. Thus, the rV(NYC)-CEA vaccine appears to be safe in rhesus monkeys. The administration of a CEA recombinant vaccine to rhesus monkeys induces both a humoral and a cell-mediated immune response directed against human CEA. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. US FDA,BUR BIOL,BETHESDA,MD 20014. NR 35 TC 87 Z9 87 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1992 VL 52 IS 24 BP 6917 EP 6925 PG 9 WC Oncology SC Oncology GA KB979 UT WOS:A1992KB97900029 PM 1458480 ER PT J AU CAJOT, JF ANDERSON, MJ LEHMAN, TA SHAPIRO, H BRIGGS, AA STANBRIDGE, EJ AF CAJOT, JF ANDERSON, MJ LEHMAN, TA SHAPIRO, H BRIGGS, AA STANBRIDGE, EJ TI GROWTH SUPPRESSION MEDIATED BY TRANSFECTION OF P53 IN HUT292DM HUMAN LUNG-CANCER CELLS EXPRESSING ENDOGENOUS WILD-TYPE P53 PROTEIN SO CANCER RESEARCH LA English DT Note ID MUTATIONS AB This study was undertaken to analyze the effect of wild-type p53 transfection on the growth potential of a human lung cancer cell line Hut292DM expressing endogenous wild-type p53. Transfection efficiencies obtained with either the wild-type or a mutant p53 complementary DNA revealed a significant decrease in the number of colonies obtained with the wild-type p53 as compared to the mutant p53 complementary DNA (27%) or control vector DNA only (20%), suggesting that wild-type p53 inhibited the growth of Hut292DM cells. A series of wild-type and mutant p53 transfection clones were then analyzed for the presence and expression of the exogenous p53 gene. Polymerase chain reaction amplification revealed that 98% of mutant p53 transfection clones analyzed contained the exogenous p53 gene as opposed to 47% for wild-type p53 clones. The majority of mutant p53 clones expressed high levels of exogenous p53 mRNA and protein as analyzed by Northern and Western blots, respectively. In contrast, all wild-type p53 clones analyzed failed to express exogenous p53 mRNA transcript or protein of a normal size. Aberrant-size p53 mRNA was detected in two wild-type p53 clones (X833.W2 and W18), and Western blot analysis revealed that these clones expressed truncated p53 proteins (M(r) 45,000 and 33,000 respectively). No difference in proliferation rates in vitro or in tumorigenic potential in nude mice were observed between mutant p53 clones or control cell lines. In contrast, a wild-type p53 clone (X833.W2) exhibited a significantly reduced tumorigenic potential in nude mice, whereas its in vitro proliferation rate was comparable to parental Hut292DM cells. The data indicate that exogenous expression of wild-type p53 is incompatible with Hut292DM lung cancer cell proliferation in vitro and suggest that p53-mediated growth control in vitro and in vivo may be dissociated and exerted by separate domains of the p53 protein. C1 UNIV CALIF IRVINE,DEPT MICROBIOL & MOLEC GENET,BLDG MED SCI 1,ROOM B210,IRVINE,CA 92717. NCI,HUMAN CARCINOGENESIS LABS,BETHESDA,MD 20892. NR 19 TC 37 Z9 37 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1992 VL 52 IS 24 BP 6956 EP 6960 PG 5 WC Oncology SC Oncology GA KB979 UT WOS:A1992KB97900037 PM 1458487 ER PT J AU GOODNIGHT, J KAZANIETZ, MG BLUMBERG, PM MUSHINSKI, JF MISCHAK, H AF GOODNIGHT, J KAZANIETZ, MG BLUMBERG, PM MUSHINSKI, JF MISCHAK, H TI THE CDNA SEQUENCE, EXPRESSION PATTERN AND PROTEIN-CHARACTERISTICS OF MOUSE PROTEIN-KINASE C-ZETA SO GENE LA English DT Article DE CDNA CLONING; GENE FAMILY; MESSENGER RNA HETEROGENEITY; MURINE BRAIN; PHORBOL; RECOMBINANT PROTEIN; RACE-PCR ID PHORBOL ESTER BINDING; HEMATOPOIETIC-CELLS; FAMILY; DOMAINS; MEMBER; LUNG; SKIN; NPKC; RNA AB A 2199-bp complementary DNA (cDNA) that encodes protein kinase C-zeta (PKC-zeta) has been isolated from mouse brain by a combination of reverse transcription and primer extension. The predicted PKC-zeta protein consists of 592 amino acids which are 99% identical to those of rat PKC-zeta. Northern blots that were probed with this cDNA revealed abundant 2200-nucleotide (nt) and 4200-nt PKC-zeta mRNAs in mouse brain in roughly equal amounts. PKC-zeta mRNA was also abundant in normal lung, kidney, and testes, and in several hemopoietic tumor lines. In all other mouse tissues and cell lines that were examined, at least faint levels of PKC-zeta mRNAs could also be detected. In tissues other than brain, the amount of PKC-zeta mRNA was less, and the smaller species generally predominated. Furthermore, in these tissues, both PKC-zeta mRNAs appear to be approximately 200 nt longer than the two mRNAs found in the brain. When the cDNA is expressed in insect cells via a baculovirus expression vector, a 75-kDa protein is synthesized which, unlike other PKC isoforms, does not bind phorbol ester, even at very high concentrations. C1 NCI,GENET LAB,MOLEC GENET SECT,BLDG 37,ROOM 2B26,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RI Mischak, Harald/E-8685-2011 NR 24 TC 55 Z9 57 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 15 PY 1992 VL 122 IS 2 BP 305 EP 311 DI 10.1016/0378-1119(92)90219-F PG 7 WC Genetics & Heredity SC Genetics & Heredity GA KG732 UT WOS:A1992KG73200009 PM 1487145 ER PT J AU CHAJUT, A SARID, R YANIV, A SMYTHERS, GW TRONICK, SR GAZIT, A AF CHAJUT, A SARID, R YANIV, A SMYTHERS, GW TRONICK, SR GAZIT, A TI THE LYMPHOPROLIFERATIVE DISEASE VIRUS OF TURKEYS REPRESENTS A DISTINCT CLASS OF AVIAN TYPE-C RETROVIRUS SO GENE LA English DT Note DE RECOMBINANT DNA; POL; REVERSE TRANSCRIPTASE; INTEGRASE; GENETIC RELATEDNESS ID NUCLEOTIDE-SEQUENCE; GENOME ORGANIZATION; EVOLUTION; ETIOLOGY AB The lymphoproliferative disease virus of turkeys (LPDV) is the etiological agent of a rapidly developing lymphoproliferative process in turkeys. To better understand the genetic relationships of LPDV to other retroviruses we determined the nucleotide sequence of its pol gene. Comparative computer analyses of the deduced amino acid sequences of the reverse transcriptase and integrase domains within pol established that LPDV represents a distinct class of avian retroviruses that is most closely related to the avian leukemia-sarcoma viruses. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 18 TC 6 Z9 6 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 DEC 15 PY 1992 VL 122 IS 2 BP 349 EP 354 DI 10.1016/0378-1119(92)90225-E PG 6 WC Genetics & Heredity SC Genetics & Heredity GA KG732 UT WOS:A1992KG73200015 PM 1283141 ER PT J AU DIAMOND, AM CRUZ, R BENCSICS, C HATFIELD, D AF DIAMOND, AM CRUZ, R BENCSICS, C HATFIELD, D TI A PSEUDOGENE FOR HUMAN GLUTATHIONE-PEROXIDASE SO GENE LA English DT Note DE GENE; EVOLUTION; UGA; SEQUENCING; CLONING; RETROTRANSPOSITION ID HUMAN CDNA SEQUENCE; GLOBIN PSEUDOGENE; SELENOCYSTEINE; GENE; IDENTIFICATION; EVOLUTION; ENZYME; SITE; TGA AB Glutathione peroxidases (GPx) serve a bioprotectivc function in the reduction of peroxides to less toxic substances. Both cellular and secreted forms of the protein have been reported, as well a number of distinct cDNA sequences. Previous efforts have described three distinct loci on human chromosomes 3, 21 and X which hybridize to a GPX cDNA and these authors have speculated that only the chromosome 3 locus encodes a functional GPX gene. This conclusion was based on mapping studies showing a precise deletion of intron sequences in the GPX loci on chromosomes 21 and X despite strong conservation among these sequences in both the coding and 3'-untranslated regions. To pursue this issue, we have isolated the chromosome 21 GPX locus by molecular cloning and determined its nucleotide sequence. Consistent with the expectations of McBride et al. [Biofactors 4 (1988) 285-2921, the sequence does reveal a highly conserved processed pseudogene. It is suggested that a retrotransposed copy of the GPX gene integrated into chromosome 21 and may have maintained activity prior to the accumulation of inactivating mutations. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. RP DIAMOND, AM (reprint author), UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,MC0085,CHICAGO,IL 60637, USA. FU NCI NIH HHS [R01 CA54364] NR 18 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 15 PY 1992 VL 122 IS 2 BP 377 EP 380 DI 10.1016/0378-1119(92)90230-M PG 4 WC Genetics & Heredity SC Genetics & Heredity GA KG732 UT WOS:A1992KG73200020 PM 1487153 ER PT J AU SAMELSON, LE KLAUSNER, RD AF SAMELSON, LE KLAUSNER, RD TI TYROSINE KINASES AND TYROSINE-BASED ACTIVATION MOTIFS - CURRENT RESEARCH ON ACTIVATION VIA THE T-CELL ANTIGEN RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID AMINO-TERMINAL DOMAIN; PROTEIN-KINASE; SIGNAL TRANSDUCTION; ZETA-CHAIN; CYTOPLASMIC DOMAINS; CD4 RECEPTOR; P56LCK; PHOSPHORYLATION; ASSOCIATION; COMPLEXES RP SAMELSON, LE (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 61 TC 273 Z9 273 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 DEC 15 PY 1992 VL 267 IS 35 BP 24913 EP 24916 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300001 PM 1459994 ER PT J AU WEST, M MIKOVITS, J PRINCLER, G LIU, YL RUSCETTI, FW KUNG, HF RAZIUDDIN AF WEST, M MIKOVITS, J PRINCLER, G LIU, YL RUSCETTI, FW KUNG, HF RAZIUDDIN TI CHARACTERIZATION AND PURIFICATION OF A NOVEL TRANSCRIPTIONAL REPRESSOR FROM HELA-CELL NUCLEAR EXTRACTS RECOGNIZING THE NEGATIVE REGULATORY ELEMENT REGION OF HUMAN IMMUNODEFICIENCY VIRUS-1 LONG TERMINAL REPEAT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEIN; RNA POLYMERASE-II; HTLV-III; GENE-EXPRESSION; TRANS-ACTIVATOR; PROMOTER-REGION; REPLICATION; SEQUENCES; ANTIGENS; COMPLEX AB Cellular transcription factors play critical roles in regulating human immunodeficiency virus (HIV) gene transcription, although the precise mechanism(s) defining their roles are not well established. Primarily it has been suggested that sequence-specific interaction of trans-activating proteins with cis-acting DNA elements plays a crucial role in regulating the target genes. The negative regulatory element (NRE) of HIV-1 long terminal repeat (LTR) is one such defined region that has been reported to down-regulate LTR-directed HIV gene expression. Information regarding the role of this region in the regulation of HIV expression is lacking. Here we describe an attempt to further characterize the role of NRE cis-elements and define any sequence-specific interaction with cellular factors. Using gel mobility shift DNA-binding and Southwestern blot assays, we have mapped a distinct region of NRE (-290 to -260, a 30-base pair (bp) domain of NRE-A) sequences of HIV-1 LTR, which recognizes a specific DNA-binding protein from HeLa cell nuclear extracts. This factor is a 38-kDa polypeptide which can be affinity-purified to near homogeneity by this 30-bp specific oligonucleotide in affinity chromatography. The cellular factor from HeLa cell nuclear extract exhibits specific interaction only with the 30-bp NRE-A domain of HIV-1 LTR and acts as a strong transcriptional repressor/inhibitor molecule in the DNA-protein gel binding, as well as in in vitro transcriptional studies with the nuclear extracts from cells with productive HIV-1 infection. To our knowledge, this is the first report of a factor recognizing a distinct segment within NRE that has been shown to exert an inhibitory effect on transcriptionally active DNA-protein "pre-initiation" complex formation, suggesting a possible role in HIV-1 gene regulation. C1 NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BIOCHEM PHYSIOL LABS,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LABS,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102, N01-CO-74101] NR 30 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1992 VL 267 IS 35 BP 24948 EP 24952 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300009 PM 1459999 ER PT J AU DUGI, KA DICHEK, HL TALLEY, GD BREWER, HB SANTAMARINAFOJO, S AF DUGI, KA DICHEK, HL TALLEY, GD BREWER, HB SANTAMARINAFOJO, S TI HUMAN LIPOPROTEIN-LIPASE - THE LOOP COVERING THE CATALYTIC SITE IS ESSENTIAL FOR INTERACTION WITH LIPID SUBSTRATES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PANCREATIC LIPASE; INTERFACIAL ACTIVATION; DENSITY LIPOPROTEINS; HYDROLYSIS; TRIBUTYRIN; SEQUENCE; PROTEINS; BINDING; ENZYME; HELIX AB Lipoprotein lipase (LPL), a key enzyme which initiates the hydrolysis of triglycerides present in chylomicrons and very low density lipoproteins, consists of multiple functional domains which are necessary for normal activity. The catalytic domain of LPL mediates the esterase function of the enzyme but separate lipid binding sites have been proposed to be involved in the interaction of LPL with emulsified lipid substrates at the water-lipid interface. Like pancreatic lipase (PL), LPL contains a surface loop covering the catalytic pocket that may modulate access of the substrate to the active site of the enzyme. Secondary structural analysis of this loop reveals a helix-turn-helix motif with two short amphipathic helices that have hydrophobic moments of 0.64 and 0.68. In order to investigate the role of the loop in the initial interaction of LPL with its substrate, we utilized site-directed mutagenesis to generate eight constructs in which the amphipathic properties of the loop were altered and expressed them in human embryonal kidney-293 cells. Reducing the amphiphilicity without changing the predicted secondary structure of the loop abolished the ability of the lipase to hydrolyze emulsified, long chain fatty acid triglycerides (triolein) but not the water soluble substrate tributyrin. Replacing the loop of LPL with the loop of hepatic lipase, which differs in 15 of 22 amino acids but is also amphiphilic, led to the expression of an enzyme that retained both triolein and tributyrin hydrolyzing activity. Substitution of the LPL loop by a short four amino acid peptide, which may allow more direct access to the active site than the 22 amino acid loop, enhanced hydrolysis of short chain fatty acid triglycerides by more than 2-fold, while the ability to hydrolyze emulsified substrates was abolished. Thus, disruption of the amphipathic structure of the LPL loop selectively decreases the hydrolysis of emulsified lipid substrate without affecting the esterase or catalytic function of the enzyme. These studies establish that the loop with its two amphipathic helices is essential for hydrolysis of long chain fatty acid substrate by LPL providing new insight into the role of the LPL loop in lipid-substrate interactions. We propose that the interaction between the lipoprotein substrates and the amphipathic helices within this loop may in part determine lipase substrate specificity. C1 NHLBI,MOLEC DIS BRANCH,BLDG 10,RM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 43 TC 92 Z9 93 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 DEC 15 PY 1992 VL 267 IS 35 BP 25086 EP 25091 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300029 PM 1460010 ER PT J AU OLIVER, KG BULLER, RML HUGHES, PJ PUTNEY, JW PALUMBO, GJ AF OLIVER, KG BULLER, RML HUGHES, PJ PUTNEY, JW PALUMBO, GJ TI INHIBITION OF AGONIST-INDUCED ACTIVATION OF PHOSPHOLIPASE-C FOLLOWING POXVIRUS INFECTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ACTIN-BINDING PROTEIN; RAT PAROTID-GLAND; VACCINIA VIRUS; REGULATORY PROTEIN; INOSITOL 1,4,5-TRISPHOSPHATE; PHOSPHOINOSITIDE METABOLISM; PANCREATOMA CELLS; FACTOR RECEPTOR; HYDROLYSIS AB Recent studies indicate that viruses may influence polyphosphoinositide levels. This study has examined the effects of vaccinia virus infection on phospholipase C activity. Infection of BS-C-1 cells, an African Green Monkey kidney cell line, or A431 cells, a human carcinoma cell line, with vaccinia virus inhibits receptor-mediated phospholipase C activation. As a consequence, agonist-mediated Ca2+ mobilization in BS-C-1 cells also was inhibited by vaccinia virus infection. Alleviation of the inhibition of phospholipase C activation was observed in vaccinia virus-infected cells treated with cycloheximide without influencing uninfected cells. Treatment of infected cells with alpha-amanitin, an inhibitor of host mRNA synthesis but not virus mRNA synthesis, failed to alleviate the inhibition of phospholipase C activation. Together these results suggest that a virus-encoded gene product mediates the inhibition of phospholipase C activation without the need of a virus-induced host factor. Analysis of the processes involved in the formation of inositol (1,4,5)-trisphosphate and mobilization of intracellular Ca2+ indicate that the vaccinia virus gene product exerts its inhibitory effects at the level of phospholipase C activity. This may occur by either directly reducing the amount of phospholipase C, reducing the specific activity of phospholipase C, or by inhibiting the association of phospholipase C with its substrate, phosphatidylinositol 4,5-bisphosphate. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP OLIVER, KG (reprint author), NIEHS,NATL TOXICOL PROGRAM,CELLULAR & MOLEC PHARMACOL,CALCIUM REGULAT SECT,MAIL DROP 7-10,RES TRIANGLE PK,NC 27709, USA. NR 53 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1992 VL 267 IS 35 BP 25098 EP 25103 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300031 PM 1460012 ER PT J AU CURRIER, SJ KANE, SE WILLINGHAM, MC CARDARELLI, CO PASTAN, I GOTTESMAN, MM AF CURRIER, SJ KANE, SE WILLINGHAM, MC CARDARELLI, CO PASTAN, I GOTTESMAN, MM TI IDENTIFICATION OF RESIDUES IN THE 1ST CYTOPLASMIC LOOP OF P-GLYCOPROTEIN INVOLVED IN THE FUNCTION OF CHIMERIC HUMAN MDR1-MDR2 TRANSPORTERS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MDR GENE FAMILY; MULTIDRUG RESISTANCE GENE; SITE-SPECIFIC MUTAGENESIS; ALTERED PATTERN; FULL-LENGTH; TUMOR-CELLS; MOUSE MDR1; CDNA; EXPRESSION; PROTEINS AB The human MDR1 gene encodes the multidrug transporter (P-glycoprotein), a multidrug efflux pump. The highly homologous MDR2 gene product does not appear to be a functional multidrug pump. We have constructed a chimeric protein in which the first intracytoplasmic loop and the third and fourth transmembrane domains of the MDR1 protein were replaced by the analogous region of MDR2. Substitution of the MDR2 sequences encompassing amino acid residues 140 to 229 resulted in 17 amino acid changes, 10 in the intracytoplasmic loop (amino acids 141-188) and 7 in the transmembrane regions. This chimeric protein was expressed on the surface of NIH 3T3 cells where it bound [H-3]azidopine but did not confer drug resistance. When only 4 residues, 165, 166, 168, and 169, were changed back to MDR1 amino acids, a functional drug transporter was recovered. When residues 165, 166, 168, and 169 from MDR2 were substituted into a functional MDR1 cDNA, the resulting construction was not able to confer drug resistance. These results indicate that the major functional differences between MDR1 and MDR2 in this region of P-glycoprotein reside in a small segment of the first intracytoplasmic loop. We also independently analyzed the effect of replacing Asn183 of MDR1 with Ser which occurs in MDR2. Substitution of Ser at position 183 in combination with Val at position 185 in P-glycoprotein resulted in a relative increase in resistance to actinomycin D, vinblastine, and doxorubicin in transfected NIH 3T3 cells. These results emphasize the importance of the first intracytoplasmic loop in P-glycoprotein in determining function and relative drug specificity of the transporter. C1 NCI,CELL BIOL LAB,9000 ROCKVILLE PIKE,BLDG 37,RM 1B22,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 35 TC 102 Z9 105 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1992 VL 267 IS 35 BP 25153 EP 25159 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300038 PM 1360983 ER PT J AU SUGIYAMA, H CHEN, P HUNTER, M TAFFS, R SITKOVSKY, M AF SUGIYAMA, H CHEN, P HUNTER, M TAFFS, R SITKOVSKY, M TI THE DUAL ROLE OF THE CAMP-DEPENDENT PROTEIN-KINASE C-ALPHA SUBUNIT IN T-CELL RECEPTOR-TRIGGERED LYMPHOCYTES-T EFFECTOR FUNCTIONS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOVINE CARDIAC-MUSCLE; AMINO-ACID-SEQUENCE; REGULATORY SUBUNIT; CATALYTIC SUBUNIT; CYCLIC-AMP; ANTISENSE OLIGONUCLEOTIDES; MEDIATED CYTOTOXICITY; GENE-EXPRESSION; INHIBITION; TRANSCRIPTION AB In order to directly evaluate the role of the cAMP-dependent protein kinase (PKA) catalytic (C) subunit in T-cell receptor- (TCR) triggered cytotoxic T-lymphocytes (CTL) effector functions, cells were studied after pretreatment with antisense oligomers complementary to mRNA for the Calpha or Cbeta subunits. Calpha subunit is shown to be predominantly expressed in CTL. In some experiments the pretreatment of the CTL with the Calpha antisense, but not with the control or Cbeta antisense oligomers, resulted in the inhibition of cAMP-independent PKA activity without significantly affecting the level of total cAMP-inducible PKA activity. In parallel assays, CTL which were pretreated with the Calpha antisense oligomer had enhanced antigen-bearing target cell-triggered-, anti-TCR monoclonal antibody-triggered-, and phorbol 12-myristate 13-acetate/A23187-triggered exocytosis of granules, as well as enhanced antigen-specific cytotoxicity. In contrast, the TCR-triggered gamma-interferon mRNA expression and gamma-interferon secretion were inhibited in Calpha antisense-pretreated CTL. These results suggest that the Calpha subunit of PKA may have a dual role in regulation of T-lymphocytes effector functions: (i) it may down-regulate TCR-triggered protein-synthesis independent responses such as cytotoxicity and exocytosis, thereby counteracting TCR-triggered activation even in the absence of the second messenger, cAMP, and (ii) the Calpha subunit activity is likely to be required for the nuclear and/or cytoplasmic events in CTL's activation involved in lymphokine synthesis and secretion. C1 NIAID, IMMUNOL LAB, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 48 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1992 VL 267 IS 35 BP 25256 EP 25263 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300054 PM 1281154 ER PT J AU OGATA, M FRYLING, CM PASTAN, I FITZGERALD, DJ AF OGATA, M FRYLING, CM PASTAN, I FITZGERALD, DJ TI CELL-MEDIATED CLEAVAGE OF PSEUDOMONAS EXOTOXIN BETWEEN ARG(279) AND GLY(280) GENERATES THE ENZYMATICALLY ACTIVE FRAGMENT WHICH TRANSLOCATES TO THE CYTOSOL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIPHTHERIA-TOXIN; ESCHERICHIA-COLI; CHIMERIC TOXINS; AERUGINOSA; SEQUENCE; EXPRESSION; DELETION; GENE; SITE AB Pseudomonas exotoxin (PE) is a three-domain toxin which is cleaved by a cellular protease within cells and then reduced to generate two prominent fragments (Ogata, M., Chaudhary, V. K., Pastan, I., and Fitz-Gerald, D. J. (1990) J. Biol. Chem. 265, 20678-20685). The N-terminal fragment is 28 kDa in size and contains the binding domain. The 37-kDa C-terminal fragment, which translocates to the cytosol, contains the translocation domain and the ADP-ribosylation domain. Cleavage followed by reduction is essential for toxicity since mutant forms of the toxin that cannot be cleaved by cells are nontoxic. Previous results with these mutants suggested that cleavage occurred in an arginine-rich (arginine residues are at positions 274, 276, and 279) disulfide loop near the beginning of the translocation domain, but the exact site of cleavage was not determined. Since very few molecules of the 37-kDa fragment are generated within cells it was not possible to determine the site of cleavage by performing a conventional N-terminal sequence analysis of the 37-kDa fragment. Two experimental approaches were used to overcome this limitation. First, existing amino acids near the cleavage sites were replaced with methionine residues; this was followed by the addition of [S-35]methionine-labeled versions of these toxins to cells. The pattern of radioactive toxin fragments recovered from the cells indicated that the toxin was cleaved either just before or just after Arg279. Second, [H-3]leucine-labeled toxin was produced and added to the cells. Sequential Edman degradations were performed on the small amount of radioactive 37-kDa fragment that could be recovered from toxin-treated cells. A peak of radioactivity in the fifth fraction indicated that leucine was the 5th amino acid on the C-terminal side of the cleavage site. This result confirmed that cleavage was between Arg279 and Gly280. C1 NCI,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. FU NCI NIH HHS [CA-12197]; NCRR NIH HHS [RR-04869] NR 26 TC 134 Z9 136 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 DEC 15 PY 1992 VL 267 IS 35 BP 25396 EP 25401 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300074 PM 1460035 ER PT J AU GLENNON, MC BIRD, GS TAKEMURA, H THASTRUP, O LESLIE, BA PUTNEY, JW AF GLENNON, MC BIRD, GS TAKEMURA, H THASTRUP, O LESLIE, BA PUTNEY, JW TI INSITU IMAGING OF AGONIST-SENSITIVE CALCIUM POOLS IN AR4-2J PANCREATOMA CELLS - EVIDENCE FOR AN AGONIST AND INOSITOL 1,4,5-TRISPHOSPHATE-SENSITIVE CALCIUM POOL IN OR CLOSELY ASSOCIATED WITH THE NUCLEAR-ENVELOPE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE CELLS; ENDOPLASMIC-RETICULUM; 3-KINASE ACTIVITY; PHOSPHOLIPASE-C; PLASMA-MEMBRANE; ACINAR-CELLS; LIVER NUCLEI; CA-2+ POOL; FURA-2; MITOCHONDRIA AB The activation of phospholipase C by hormones and neurotransmitters activates a complex combination of Ca2+ release and accumulation by intracellular organelles. Previously, we demonstrated that, in some cell types, the fluorescent Ca2+ indicator, fura-2, can be loaded into intracellular, agonist-sensitive Ca2+ pools (Glennon, M. C., Bird, G. St. J., Kwan, C.-Y., and Putney, J. W., Jr. (1992) J. Biol. Chem. 267, 8230-8233). In the current study, we have attempted to exploit this phenomenon by employing digital fluorescence imaging of compartmentalized fura-2 to investigate the localization and function of the major intracellular sites of Ca2+ regulation in AR4-2J pancreatoma cells. By judicious use of a surface receptor agonist together with the Ca2+-ATPase inhibitor, thapsigargin, cellular regions were identified whose behavior indicates that they contain the sites of agonist- and inositol 1,4,5-trisphosphate-mediated intracellular Ca2+ release. These regions were located throughout the cell and may include the nuclear envelope. They were distinct in locus and behavior from two other regions, which counterstained with fluorescent markers for nuclei and mitochondria. Fura-2 in mitochondrial regions reported low resting levels of [Ca2+], and revealed that organelles in these regions accumulate and retain Ca2+ after agonist activation. These findings demonstrate that fluorescent Ca2+ indicators can be employed to directly monitor changes in [Ca2+] in the major Ca2+-regulating organelles, and provide the first in situ visualization and localization of the major sites of Ca2+ regulation in cells. C1 NIEHS,CELLULAR & MOLEC PHARMACOL,CALCIUM REGULAT SECT,POB 12233,RES TRIANGLE PK,NC 27709. UNIV COPENHAGEN HOSP,RIGSHOSP,DEPT CLIN CHEM,DK-2100 COPENHAGEN,DENMARK. UNIV COPENHAGEN HOSP,RIGSHOSP,THROMBOSIS GRP,DK-2100 COPENHAGEN,DENMARK. NR 46 TC 41 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 DEC 15 PY 1992 VL 267 IS 35 BP 25568 EP 25575 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300098 PM 1460052 ER PT J AU WEISZ, A MARX, P SHARF, R APPELLA, E DRIGGERS, PH OZATO, K LEVI, BZ AF WEISZ, A MARX, P SHARF, R APPELLA, E DRIGGERS, PH OZATO, K LEVI, BZ TI HUMAN INTERFERON CONSENSUS SEQUENCE BINDING-PROTEIN IS A NEGATIVE REGULATOR OF ENHANCER ELEMENTS COMMON TO INTERFERON-INDUCIBLE GENES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLASS-I GENE; INDUCED TRANSCRIPTION; NUCLEAR FACTORS; GAMMA; CELLS; INDUCTION; ALPHA; IRF-1; IFN; EXPRESSION AB The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. H-ICSBP shares high sequence homology with its murine cognate. The derived sequence of H-ICSBP reveals restricted homology within the first 120 amino acids to three other interferon regulatory factors, IRF-1, IRF-2, and ISGF3gamma. Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. H-ICSBP is expressed exclusively in cell lines of hematopoietic origin. The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. Furthermore, either interferon-gamma (IFN-gamma) or IFN-beta can alleviate the repression mediated by ICSBP. Therefore, ICSBP may be involved in maintaining submaximal transcriptional activity of IFN-inducible genes in hematopoietic cells. IFN treatment would then alleviate repression allowing maximal transcriptional activity of these genes. C1 NICHHD,BETHESDA,MD 20892. RP LEVI, BZ (reprint author), TECHNION ISRAEL INST TECHNOL,DEPT FOOD ENGN & BIOTECHNOL,IL-32000 HAIFA,ISRAEL. NR 43 TC 129 Z9 131 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1992 VL 267 IS 35 BP 25589 EP 25596 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300101 PM 1460054 ER PT J AU JIANG, HX COOPER, B ROBEY, FA GEWURZ, H AF JIANG, HX COOPER, B ROBEY, FA GEWURZ, H TI DNA BINDS AND ACTIVATES COMPLEMENT VIA RESIDUES 14-26 OF THE HUMAN C1Q A-CHAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCES; 1ST COMPONENT; SUBCOMPONENT C1Q; REGIONS PRESENT; CLQ; COMPLEXES; ANTIBODY; LOCATION; PROTEINS; GAMMA AB The mechanism by which DNA activates the classical complement pathway was investigated, with emphasis upon the C1q binding sites involved. DNA bound to both the collagen-like and globular regions of C1q. Binding reactivity with DNA was retained after reduction/alkylation and sodium dodecyl sulfate treatment of C1q. DNA bound preferentially to the A chain of C1q. Binding sites for DNA were localized by using synthetic C1q A chain peptides to two cationic regions within residues 14-26 and 76-92, respectively. Peptides 14-26 and 76-92 avidly bound DNA in enzyme-linked immunosorbent and gel shift assays. Peptide 14-26 also precipitated with DNA and blocked its ability to bind C1q and activate C. Replacement of the two prolines with alanines or scrambling the order of the amino acids resulted in loss of ability of peptide 14-26 to inhibit C1q binding and complement activation by DNA; similar investigations showed a sequence specificity for peptide 76-92 as well. These experiments identify C1q A chain residues 14-26 as the major site, and residues 76-92 as a secondary site, through which DNA binds C1q and activates the classical complement pathway, and demonstrate that a peptide identical to residues 14-26 can modulate C1q binding and complement activation by DNA. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RP JIANG, HX (reprint author), RUSH MED COLL,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612, USA. NR 42 TC 78 Z9 81 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1992 VL 267 IS 35 BP 25597 EP 25601 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB603 UT WOS:A1992KB60300102 PM 1460055 ER PT J AU ZHOU, HX BAGCHI, B PAPAZYAN, A MARONCELLI, M AF ZHOU, HX BAGCHI, B PAPAZYAN, A MARONCELLI, M TI SOLVATION DYNAMICS IN A BROWNIAN DIPOLE LATTICE - A COMPARISON BETWEEN THEORY AND COMPUTER-SIMULATION SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MEAN SPHERICAL APPROXIMATION; TIME-DEPENDENT FLUORESCENCE; POLAR LIQUIDS; NONEQUILIBRIUM SOLVATION; POLARIZATION RELAXATION; MOLECULAR THEORY; STOKES SHIFT; SOLVENT; MODEL; ION AB Papazyan and Maroncelli [J. Chem. Phys. 95, 9219 (1991)] recently reported computer simulations of solvation dynamics of an ion in a Brownian dipole lattice solvent. In the present article we compare these results to predictions of a number of theories of solvation dynamics in the diffusive limit. The frequency-dependent dielectric response functions needed as input to many of the theories are derived from further simulations of the lattice solvent [H. X. Zhou and B. Bagchi, J. Chem. Phys. 97, 3610 (1992)]. When properly applied, all of the currently popular molecular theories yield reasonable predictions for the time scale of the solvation response. The dynamical MSA model [P. G. Wolynes, J. Chem. Phys. 86, 5133 (1987)] and the memory function theory of Fried and Mukamel [J. Chem. Phys. 93, 932 (1990)) both provide nearly quantitative agreement with all aspects of the solvation dynamics observed in these simulations. C1 PENN STATE UNIV,DEPT CHEM,UNIV PK,PA 16802. RP ZHOU, HX (reprint author), NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Maroncelli, Mark/A-1800-2012; Zhou, Huan-Xiang/M-5170-2016; OI Zhou, Huan-Xiang/0000-0001-9020-0302; BAGCHI, BIMAN/0000-0002-7146-5994 NR 41 TC 45 Z9 45 U1 0 U2 3 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 DEC 15 PY 1992 VL 97 IS 12 BP 9311 EP 9390 DI 10.1063/1.463307 PG 80 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA KE637 UT WOS:A1992KE63700052 ER PT J AU MORRIS, SC LEES, A INMAN, J FINKELMAN, FD AF MORRIS, SC LEES, A INMAN, J FINKELMAN, FD TI ROLE OF ANTIGEN-SPECIFIC T-CELL HELP IN THE GENERATION OF INVIVO ANTIBODY-RESPONSES .1. ANTIGEN-SPECIFIC T-CELL HELP IS REQUIRED TO GENERATE A POLYCLONAL IGG1 RESPONSE IN ANTI-IGD ANTIBODY-INJECTED MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE IMMUNE-SYSTEM; RESTING B-CELLS; STIMULATORY FACTOR-I; MONOCLONAL-ANTIBODIES; LYMPHOCYTES-B; CROSS-LINKING; SURFACE-IMMUNOGLOBULIN; INCREASED EXPRESSION; FUNCTIONAL-ANALYSIS; RECEPTOR ANTIBODY AB A system in which injection of mice with an antibody to mouse IgD that they recognize as foreign stimulates a large, T cell-dependent IgG response was used to study whether Ag-specific T cell help is required to stimulate polyclonal (non-Ag-specific) IgG production in vivo. Igh(a) x Igh(b) allotype heterozygous mice were injected with a conjugate of a foreign Ag coupled to a mAb specific for one of the two IgD allotypes expressed in these mice. This conjugate cross-links mIgD on B cells that express the recognized allotype. These cells process the conjugate and present the foreign Ag to Ag-specific T lymphocytes, which become activated. Thus, B cells of the recognized allotype can be stimulated by cross-linking of their mIgD, Ag-specific T cell help, non-Ag-specific cytokines, and non-Ag-specific contact with activated T cells. In contrast, B cells that express the Igh allotype not recognized by the Ag-anti-IgD antibody conjugate (bystander B cells) can be stimulated in this system only by non-Ag-specific cytokines and non-Ag-specific contact with activated T cells. Although both recognized and bystander B cells in conjugate-injected mice demonstrated substantial increases in size and Ia expression, only the recognized B cells were induced to synthesize DNA and to make a substantial polyclonal Ig response. Bystander B cells still failed to secrete IgG when mice were injected with an anti-IgD-Ag conjugate specific for the other Igh allotype as well as a mAb that cross-linked IgD of the bystander B cell allotype. These observations demonstrate that although non-Ag-specific cytokine and contact-mediated T cell help are sufficient to induce B cells to increase in size and Ia expression in anti-IgD antibody-injected mice, Ag-specific T cell help is required to stimulate the generation of an IgG response in these mice. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP MORRIS, SC (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT MED,ROOM A3060,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. FU NIAID NIH HHS [R01-AI21328] NR 76 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1992 VL 149 IS 12 BP 3836 EP 3844 PG 9 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200009 PM 1281190 ER PT J AU MURPHY, WJ DURUM, SK LONGO, DL AF MURPHY, WJ DURUM, SK LONGO, DL TI ROLE OF NEUROENDOCRINE HORMONES IN MURINE T-CELL DEVELOPMENT - GROWTH-HORMONE EXERTS THYMOPOIETIC EFFECTS INVIVO SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DWARF MICE; SNELL; LYMPHOCYTES; GENERATION AB Growth hormone (GH) and other neuroendocrine mediators have been implicated previously in T cell development. We therefore examined thymic development in DW/J dwarf mice. DW/J mice lack acidophilic anterior pituitary cells and consequently are totally deficient in the production of GH, as well as other neuroendocrine hormones. DW/J dwarf mice had greatly hypoplastic thymi that continued to decrease in size as the mice aged. Characterization of the different T cell subpopulations within the thymi of dwarf mice indicated a deficiency in CD4+/CD8+ double-positive thymocytes. This deficiency of progenitor cells became more complete as the mice aged culminating in the total disappearance of this subpopulation in some dwarf mice >3 mo of age. Analysis of the lymph nodes indicated that a population of double-positive (CD4/CD8) T cells appeared in some mice concurrent with the disappearance of double-positive cells in the thymus suggesting that these thymocytes may have migrated to the periphery. However, peripheral T cells from dwarf mice did exhibit Ag-specific responses indicating that these mice have functional T cells. Treatment of the mice with recombinant human GH, which binds both murine growth hormone receptors and murine prolactin receptors, or ovine GH, which binds murine growth hormone receptors but not murine prolactin receptors, resulted in an increase in thymic size and the reappearance of the CD4+/CD8+ double-positive cells within the thymus. Additionally, after GH treatment, the double-positive cells disappeared from the lymph nodes. The thymi of mice treated with GH failed to attain normal size but did develop a normal distribution of T cell progenitors. Thus, GH exerts significant thymopoietic effects in vivo. Neuroendocrine hormones may be important for normal T cell differentiation to occur within the murine thymus. C1 NCI,FREDERICK CANC RES & DEV CTR,OFF ASSOCIATE DIRECTOR,BETHESDA,MD 20892. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BETHESDA,MD 20892, USA. NR 20 TC 110 Z9 111 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1992 VL 149 IS 12 BP 3851 EP 3857 PG 7 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200011 PM 1460277 ER PT J AU VANSEVENTER, GA BONVINI, E YAMADA, H CONTI, A STRINGFELLOW, S JUNE, CH SHAW, S AF VANSEVENTER, GA BONVINI, E YAMADA, H CONTI, A STRINGFELLOW, S JUNE, CH SHAW, S TI COSTIMULATION OF T-CELL RECEPTOR CD3-MEDIATED ACTIVATION OF RESTING HUMAN CD4+ T-CELLS BY LEUKOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 LIGAND INTERCELLULAR CELL-ADHESION MOLECULE-1 INVOLVES PROLONGED INOSITOL PHOSPHOLIPID HYDROLYSIS AND SUSTAINED INCREASE OF INTRACELLULAR CA2+ LEVELS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; MONOCLONAL-ANTIBODY; MEDIATED ACTIVATION; CYTOPLASMIC DOMAIN; GROWTH-FACTOR; BETA-SUBUNIT; B-CELLS; ICAM-1; LFA-1 AB Activation of resting human CD4+ T cells mediated by mAb ligation of the TCR/CD3 complex requires costimulatory signals to result in proliferation; these can be provided by intercellular cell adhesion molecule-1 (ICAM-1, CD54) a natural ligand of leukocyte function-associated Ag-1 (LFA-1, CD11a/CD18). We analyzed early signaling events involved in T cell activation to determine the contribution by the LFA-1/ICAM-1 interaction. We studied in detail the hydrolysis of phosphatidylinositol(4,5)bisphosphate and intracellular levels of free Ca2+ during stimulation with beads coated with the CD3 mAb OKT3 alone or in combination with purified ICAM-1 protein. Our investigations show no response to LFA-1/ICAM-1 alone, but that costimulation by LFA-1/ICAM-1 interaction induces prolonged inositol phospholipid hydrolysis (up to 4 h), resulting in generation of both inositol(1,4,5)phosphate3 and inositol(1,3,4,5)phosphate4 and their derivatives. Based on studies with cycloheximide, this costimulatory effect of prolonged inositol phospholipid hydrolysis appears dependent in part on de novo protein synthesis. A sustained increase in intracellular levels of free Ca2+ level is also observed after LFA-1/ICAM-1 costimulation, which is at least partly dependent on extracellular sources of Ca2+. Kinetic studies indicate that costimulation requires a minimal period of 4 h of LFA-1/ICAM-1 interaction to provide maximal costimulation for OKT3-mediated T cell proliferation. Thus, the necessary costimulation required for OKT3-mediated proliferation in this model system may be provided by an extended LFA-1/ICAM-1 interaction that in combination with OKT3 mAb leads to signal-transducing events, resulting in prolonged phospholipase C activation and phosphatidylinositol(4,5)bisphosphate hydrolysis, and a sustained increase in intracellular levels of free Ca2+. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NR 53 TC 114 Z9 114 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1992 VL 149 IS 12 BP 3872 EP 3880 PG 9 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200014 PM 1360995 ER PT J AU GRIMALDI, JC TORRES, R KOZAK, CA CHANG, R CLARK, EA HOWARD, M COCKAYNE, DA AF GRIMALDI, JC TORRES, R KOZAK, CA CHANG, R CLARK, EA HOWARD, M COCKAYNE, DA TI GENOMIC STRUCTURE AND CHROMOSOMAL MAPPING OF THE MURINE CD40 GENE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NERVE GROWTH-FACTOR; HUMAN URINARY-BLADDER; FACTOR RECEPTOR GENE; HUMAN B-CELLS; HUMAN LYMPHOCYTES-B; MOLECULAR-CLONING; MONOCLONAL-ANTIBODIES; ACTIVATION MOLECULE; DENDRITIC CELLS AB The B cell-associated surface molecule, CD40, is likely to play a central role in the expansion of Ag-stimulated B cells, and their interaction with activated Th cells. In our study we have isolated genomic clones of murine CD40 from a mouse liver genomic DNA library. Comparison with the murine CD40 cDNA sequence revealed the presence of nine exons that together contain the entire murine CD40 coding region, and span approximately 16.3 kb of genomic DNA. The intron/exon structure of the CD40 gene resembles that of the low affinity nerve growth factor receptor gene, a close homolog of both human and murine CD40. In both cases the functional domains of the receptor molecules are separated onto different exons throughout the genes. Southern blot analysis demonstrated that murine CD40 is a single copy gene that maps in the distal region of mouse chromosome 2. C1 DNAX INC,MOLEC & CELLULAR BIOL RES INST,DEPT IMMUNOL,901 CALIF AVE,PALO ALTO,CA 94304. UNIV WASHINGTON,DEPT MICROBIOL SC42,SEATTLE,WA 98195. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RI Clark, Edward/K-3462-2012 NR 59 TC 55 Z9 58 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1992 VL 149 IS 12 BP 3921 EP 3926 PG 6 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200020 PM 1281194 ER PT J AU HORGAN, KJ LUCE, GEG TANAKA, Y SCHWEIGHOFFER, T SHIMIZU, Y SHARROW, SO SHAW, S AF HORGAN, KJ LUCE, GEG TANAKA, Y SCHWEIGHOFFER, T SHIMIZU, Y SHARROW, SO SHAW, S TI DIFFERENTIAL EXPRESSION OF VLA-ALPHA-4 AND VLA-BETA-1 DISCRIMINATES MULTIPLE SUBSETS OF CD4+CD45R0+ MEMORY T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; ADHESION MOLECULES; HELPER-INDUCER; LYMPHOCYTES-T; INTEGRIN; VLA-4; ACTIVATION; FIBRONECTIN; RECEPTOR; COSTIMULATION AB Given the importance of adhesion in T cell development, we have undertaken systematic flow cytometric analysis of CD4 T cells to determine relationships between the developmentally regulated marker CD45R0 and adhesion receptors (five VLA integrin chains). The most important findings are that: 1) expression of alpha3, alpha5, and alpha6 are closely co-regulated with beta1 on CD4 cells, while regulation of VLA-alpha4 is quite discordant. 2) CD45R0- cells, generally understood to be naive cells, have low homogeneous expression of VLA-alpha3, VLA-alpha4, VLA-alpha5, VLA-alpha6, and beta1 integrin chains; studies of cord blood CD4 cells confirm the low homogeneous expression of alpha4 and, beta1 on naive cells. 3) In marked contrast, CD45R0+ cells, generally understood to be memory cells, show not only an overall increase in expression of these integrins (relative to CD45R0- cells) but also heterogeneity. Dramatic heterogeneity is revealed when the markers VLA-alpha4 and beta1 are analyzed together. Many CD45R0+ cells show increased levels of both VLA-alpha4 and VLA-beta1; however, some have increased levels principally of either VLA-beta1 or VLA-alpha4. We hypothesize that T cells becoming memory cells in different microenvironments specialize their integrin phenotype, thereby acquiring distinctive functional and homing capacities; in this process, VLA-4 (CD49d) appears to play a unique role. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892. NR 44 TC 43 Z9 43 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1992 VL 149 IS 12 BP 4082 EP 4087 PG 6 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200043 PM 1360997 ER PT J AU WEISS, GH DAYAN, I HAVLIN, S KIEFER, JE LARRALDE, H STANLEY, HE TRUNFIO, P AF WEISS, GH DAYAN, I HAVLIN, S KIEFER, JE LARRALDE, H STANLEY, HE TRUNFIO, P TI SOME RECENT VARIATIONS ON THE EXPECTED NUMBER OF DISTINCT SITES VISITED BY AN N-STEP RANDOM-WALK SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article ID MEDIA AB Asymptotic forms for the expected number of distinct sites visited by an n-step random walk, being calculable for many random walks, have been used in a number of analyses of physical models. We describe three recent extensions of the problem, the first replacing the single random walker by N --> infinity random walkers, the second to the study of a random walk in the presence of a trapping site, and the third to a random walk in the presence of a trapping hyperplane. C1 BAR ILAN UNIV, DEPT PHYS, IL-52100 RAMAT GAN, ISRAEL. BOSTON UNIV, CTR POLYMER STUDIES, BOSTON, MA 02215 USA. RP NIH, BETHESDA, MD 20892 USA. NR 21 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 EI 1873-2119 J9 PHYSICA A JI Physica A PD DEC 15 PY 1992 VL 191 IS 1-4 BP 479 EP 490 DI 10.1016/0378-4371(92)90572-8 PG 12 WC Physics, Multidisciplinary SC Physics GA KF666 UT WOS:A1992KF66600077 ER PT J AU HAILE, DJ ROUAULT, TA HARFORD, JB KENNEDY, MC BLONDIN, GA BEINERT, H KLAUSNER, RD AF HAILE, DJ ROUAULT, TA HARFORD, JB KENNEDY, MC BLONDIN, GA BEINERT, H KLAUSNER, RD TI CELLULAR-REGULATION OF THE IRON-RESPONSIVE ELEMENT BINDING-PROTEIN - DISASSEMBLY OF THE CUBANE IRON-SULFUR CLUSTER RESULTS IN HIGH-AFFINITY RNA-BINDING SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ACONITASE (IN)ACTIVATION; SUBSTRATE PROTECTION; THIOL EFFECT ID FERRITIN MESSENGER-RNA; 3' UNTRANSLATED REGION; TRANSLATIONAL REGULATION; IRE-BP; ACONITASE; PURIFICATION; EXPRESSION; SEQUENCE AB The translation of ferritin mRNA and degradation of transferrin receptor mRNA are regulated by the interaction of an RNA-binding protein, the iron-responsive element binding protein (IRE-BP), with RNA stem-loop structures known as iron-responsive elements (IREs) contained within these transcripts. IRE-BP produced in iron-replete cells has aconitase (EC 4.2.1.3) activity. The protein shows extensive sequence homology with mitochondrial aconitase, and sequences of peptides prepared from cytosolic aconitase are identical with peptides of IRE-BP. As an active aconitase, IRE-BP is expected to have an Fe-S cluster, in analogy to other aconitases. This Fe-S cluster has been implicated as the region of the protein that senses intracellular iron levels and accordingly modifies the ability of the IRE-BP to interact with IREs. Expression of the IRE-BP in cultured cells has revealed that the IRE-BP functions either as an active aconitase, when the cells are iron-replete, or as an active RNA-binding protein, when the cells are iron-depleted. We compare properties of purified authentic cytosolic aconitase from beef liver with those of IRE-BP from tissue culture cells and establish that characteristics of the physiologically relevant form of the protein from iron-depleted cells resemble those of cytosolic aconitase apoprotein. We demonstrate that loss of the labile fourth iron atom of the Fe-S cluster results in loss of aconitase activity, but that more extensive cluster alteration is required before the IRE-BP acquires the capacity to bind RNA with the affinity seen in vivo. These results are consistent with a model in which the cubane Fe-S cluster is disassembled when intracellular iron is depleted. C1 MED COLL WISCONSIN,DEPT BIOCHEM,MILWAUKEE,WI 53226. MED COLL WISCONSIN,BIOPHYS RES INST,MILWAUKEE,WI 53226. UNIV WISCONSIN,CTR WATER RESOURCES,MADISON,WI 53706. RP HAILE, DJ (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [R01 GM34812] NR 29 TC 274 Z9 276 U1 2 U2 5 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1992 VL 89 IS 24 BP 11735 EP 11739 DI 10.1073/pnas.89.24.11735 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400020 PM 1281544 ER PT J AU CUNNINGHAM, NS PARALKAR, V REDDI, AH AF CUNNINGHAM, NS PARALKAR, V REDDI, AH TI OSTEOGENIN AND RECOMBINANT BONE MORPHOGENETIC PROTEIN-2B ARE CHEMOTACTIC FOR HUMAN MONOCYTES AND STIMULATE TRANSFORMING GROWTH FACTOR-BETA-1 MESSENGER-RNA EXPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BONE INDUCTION; CARTILAGE; DEVELOPMENTAL CASCADE; BONE REPAIR ID FACTOR-TYPE-BETA; TGF-BETA; EXTRACELLULAR-MATRIX; PHENOTYPES INVITRO; COMPLEMENTARY-DNA; IV COLLAGEN; DIFFERENTIATION; FIBROBLASTS; CELLS; RECEPTORS AB Subcutaneous implantation of demineralized bone matrix initiates a sequence of developmental events, which culminate in endochondral bone formation. During early stages of development of matrix-induced implants, ED1, Ia-positive monocytes-macrophages were observed, suggesting that in the initial phases of the endochondral bone formation cascade, the bone-inductive protein osteogenin and related bone morphogenetic proteins (BMPs) might serve as potent chemoattractants to recruit circulating monocytes. In this investigation, we demonstrate that at concentrations of 10-100 fg/ml (0.3-3 fM), native bovine osteogenin and recombinant human BMP-2B (rhBMP-2B) induce the directed migration of human blood monocytes in vitro. This chemotactic response was associated with expression of BMP binding sites (receptors) on monocytes. About 750 receptors per cell were detected with an apparent dissociation constant of 200 pM. Both osteogenin and rhBMP-2B at higher concentrations (0.1-30 ng/ml) stimulated mRNA expression for an additional regulatory molecule, type beta1 transforming growth factor (TGF-beta1) in human monocytes. TGF-beta1, in turn, is known to induce a cascade of events leading to matrix generation. Monocytes stimulated by TGF-beta are known to secrete a number of chemotactic and mitogenic cytokines that recruit endothelial and mesenchymal cells and promote their synthesis of collagen and associated matrix constituents. TGF-beta1 in concert with these other cytokines and matrix components regulates chemotaxis, mesenchymal proliferation, differentiation, angiogenesis, and controlled synthesis of extracellular matrix. Our results demonstrate that osteogenin and related BMPs through their profound effects on monocyte recruitment and cytokine synthesis may promote additional successive steps in the endochondral bone formation cascade. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ORTHOPAED SURG,MUSCULOSKELETAL CELL BIOL LAB,ROSS RES BLDG,BALTIMORE,MD 21205. NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. RP REDDI, AH (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT ORTHOPAED SURG,MUSCULOSKELETAL CELL BIOL LAB,ROSS RES BLDG,BALTIMORE,MD 21205, USA. NR 49 TC 194 Z9 197 U1 1 U2 4 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1992 VL 89 IS 24 BP 11740 EP 11744 DI 10.1073/pnas.89.24.11740 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400021 PM 1334547 ER PT J AU HOFFMAN, PM DHIBJALBUT, S MIKOVITS, JA ROBBINS, DS WOLF, AL BERGEY, GK LOHREY, NC WEISLOW, OS RUSCETTI, FW AF HOFFMAN, PM DHIBJALBUT, S MIKOVITS, JA ROBBINS, DS WOLF, AL BERGEY, GK LOHREY, NC WEISLOW, OS RUSCETTI, FW TI HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I INFECTION OF MONOCYTES AND MICROGLIAL CELLS IN PRIMARY HUMAN CULTURES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; TROPICAL SPASTIC PARAPARESIS; HTLV-I; CYTOTOXIC LYMPHOCYTES; NEUROLOGICAL DISEASE; GROWTH-FACTOR; GENE; EXPRESSION; ACTIVATION AB The pathogenesis of progressive spastic paraparesis [HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)], a serious consequence of human T-cell leukemia virus type I (HTLV-I) infection, is unclear. T and B lymphocytes can be naturally infected by HTLV-I, but the susceptibility to HTLV-I infection of other cell types that could contribute to the pathogenesis of HAM/TSP has not been determined. We found that a human monocyte cell line (THP-1), primary human peripheral blood monocytes, and isolated microglial cells but not astrocytes or oligodendroglial cells derived from adult human brain were infected by HTLV-I in vitro. Infection with HTLV-I enhanced the secretion of interleukin 6 in human microglial cell-enriched cultures but did not stimulate the release of interleukin 1 from monocytes or microglial cells. Tumor necrosis factor alpha production was stimulated by HTLV-I infection of monocytes and microglial cells and could be enhanced by suboptimal amounts of lipopolysaccharide. Since both tumor necrosis factor alpha and interleukin 6 have been implicated in inflammatory demyelination and gliosis, our findings suggest that human microglial cells and monocytes infected with and activated by HTLV-I could play a role in the pathogenesis of HAM/TSP. C1 UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT SURG NEUROSURG,BALTIMORE,MD 21201. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS DRUG TESTING LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. RP HOFFMAN, PM (reprint author), VET AFFAIRS MED CTR,RETROVIRUS RES CTR,BALTIMORE,MD 21218, USA. FU NCI NIH HHS [N01-CO-74102] NR 46 TC 94 Z9 94 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1992 VL 89 IS 24 BP 11784 EP 11788 DI 10.1073/pnas.89.24.11784 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400030 PM 1465399 ER PT J AU CITRON, BA DAVIS, MD MILSTIEN, S GUTIERREZ, J MENDEL, DB CRABTREE, GR KAUFMAN, S AF CITRON, BA DAVIS, MD MILSTIEN, S GUTIERREZ, J MENDEL, DB CRABTREE, GR KAUFMAN, S TI IDENTITY OF 4A-CARBINOLAMINE DEHYDRATASE, A COMPONENT OF THE PHENYLALANINE HYDROXYLATION SYSTEM, AND DCOH, A TRANSREGULATOR OF HOMEODOMAIN PROTEINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHENYLALANINE HYDROXYLASE; 4A-HYDROXYTETRAHYDROPTERIN DEHYDRATASE; TETRAHYDROBIOPTERIN; HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; HOMEODOMAIN REGULATORY FACTOR ID HUMAN DIHYDROPTERIDINE REDUCTASE; RAT-LIVER; 7-SUBSTITUTED PTERINS; CDNA CLONE; SEQUENCE; ENZYME; TETRAHYDROBIOPTERIN; DIMERIZATION; STIMULATOR; SITES AB The principal pathway for the metabolism of phenylalanine in mammals is via conversion to tyrosine in a tetrahydrobiopterin-dependent hydroxylation reaction occurring predominantly in the liver. Recently, the proposal that certain hyperphenylalaninemic children may have a deficiency of carbinolamine dehydratase, a component of the phenylalanine hydroxylation system, has widened the interest in this area of metabolism. Upon cloning and sequencing the dehydratase, we discovered that this protein is identical to DCoH, the cofactor which regulates the dimerization of hepatic nuclear factor 1alpha, a homeodomain transcription factor. The identity of the nuclear and cytoplasmic proteins is demonstrated by size, immunoblotting, stimulation of phenylalanine hydroxylase, and dehydratase activity. The evolution of the dual functions of regulation of phenylalanine hydroxylation activity and transcription activation in a single polypeptide is unprecedented. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. STANFORD UNIV,BECKMAN CTR MOLEC & GENET MED,SCH MED,HOWARD HUGHES INST,STANFORD,CA 94305. RP CITRON, BA (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 29 TC 101 Z9 103 U1 0 U2 4 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1992 VL 89 IS 24 BP 11891 EP 11894 DI 10.1073/pnas.89.24.11891 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400052 PM 1465414 ER PT J AU GOODMAN, SD NICHOLSON, SC NASH, HA AF GOODMAN, SD NICHOLSON, SC NASH, HA TI DEFORMATION OF DNA DURING SITE-SPECIFIC RECOMBINATION OF BACTERIOPHAGE-LAMBDA - REPLACEMENT OF IHF PROTEIN BY HU PROTEIN OR SEQUENCE-DIRECTED BENDS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA BEND; NUCLEOPROTEIN COMPLEX; CURVED DNA ID INTEGRATION HOST FACTOR; ESCHERICHIA-COLI; BINDING-SITES; COHESIVE ENDS; REPLICATION; POLYMERASE; ORIGIN; CLEAVAGE; PRODUCT; GENE AB Escherichia coli IHF protein is a prominent component of bacteriophage lambda integration and excision that binds specifically to DNA. We find that the homologous protein HU, a nonspecific DNA binding protein, can substitute for IHF during excisive recombination of a plasmid containing the prophage attachment sites attL and attR but not during integrative recombination between attP and attB. We have examined whether IHF and HU function in excisive recombination is mediated through DNA bending. Our strategy has been to construct chimeric attachment sites in which IHF binding sites are replaced by an alternative source of DNA deformation. Previously, we demonstrated that properly phased bends can substitute for the binding of IHF at one site in attP. Although this result is highly suggestive of a critical role of IHF-promoted bending in lambda integration, its interpretation is obscured by the continued need for IHF binding to the remaining IHF sites of these constructs. In the present work, we engineered a population of sequence-directed bends in the vicinity of the two essential IHF sites found in attR and attL. Even in the absence of IHF or HU, pairs of these attachment sites with properly phased bends are active for both in vitro and in vivo excision. This success, although tempered by the limited efficiency of these systems, reinforces our interpretation that IHF functions primarily as an architectural element. RP GOODMAN, SD (reprint author), NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Goodman, Steven/C-5732-2013 NR 34 TC 105 Z9 105 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1992 VL 89 IS 24 BP 11910 EP 11914 DI 10.1073/pnas.89.24.11910 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400056 PM 1465417 ER PT J AU CAROTHERS, AM ZHEN, WP MUCHA, J ZHANG, YJ SANTELLA, RM GRUNBERGER, D BOHR, VA AF CAROTHERS, AM ZHEN, WP MUCHA, J ZHANG, YJ SANTELLA, RM GRUNBERGER, D BOHR, VA TI DNA STRAND-SPECIFIC REPAIR OF (+/-)-3-ALPHA,4-BETA-DIHYDROXY-1-ALPHA,2-ALPHA-EPOXY-1,2,3,4-TETRAHYDROB ENZO[C]PHENANTHRENE ADDUCTS IN THE HAMSTER DIHYDROFOLATE-REDUCTASE GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE POLYCYCLIC AROMATIC HYDROCARBON; CHO CELLS; ADDUCT QUANTITATION; UVRABC EXCISION NUCLEASE; P-32-POSTLABELING ID DIPLOID HUMAN FIBROBLASTS; REGION DIOL-EPOXIDES; MAMMALIAN-CELLS; DHFR GENE; CHO CELLS; P53 GENE; MUTATION-INDUCTION; EXCISION REPAIR; CODING REGION; BASE CHANGES AB We evaluated the formation and removal of (+/-)-3alpha,4beta-dihydroxy-1alpha,2alpha-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene (BcPHDE)-DNA adducts in two Chinese hamster ovary (CHO) cell lines. One line of repair-proficient cells (MK42) carries a stable 150-fold amplification of the dihydrofolate reductase (DHFR) locus. The other line of repair-deficient cells (UV-5) is diploid for this gene and is defective in excision of bulky DNA lesions. Two methods were used to quantitate adduct levels in treated cells: Escherichia coli UvrABC excision nuclease cleavage and P-32-postlabeling. DNA repair was examined in the actively transcribed DHFR gene, in an inactive region located 25 kilobases downstream, and in the overall genome. Between 8 and 24 hr after BcPHDE exposure, preferential repair of the DHFR gene compared to the non-coding region was apparent in MK42 cells. This gene-specific repair was, associated with adduct removal from the DHFR transcribed strand. However, UV-5 cells showed no lesion reduction from this strand of the gene. By both quantitation methods, regions accessible to repair in MK42 cells showed a 2-fold reduction in DNA adduct levels-by 24 hr. That the decline in adducts reflects genomic repair was demonstrated by the constant damage level remaining in UV-5 cells. Since BcPHDE-induced mutations in DHFR apparently arise from adducted purines on the nontranscribed strand, results from the present study support the idea that a consequence of strand-specific repair is strand-biased mutations. C1 COLUMBIA UNIV,CTR COMPREHENS CANC,NEW YORK,NY 10032. COLUMBIA UNIV,DIV ENVIRONM SCI,NEW YORK,NY 10032. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP CAROTHERS, AM (reprint author), COLUMBIA UNIV,INST CANC RES,NEW YORK,NY 10032, USA. FU NCI NIH HHS [CA39547, CA21111] NR 41 TC 26 Z9 26 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1992 VL 89 IS 24 BP 11925 EP 11929 DI 10.1073/pnas.89.24.11925 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400059 PM 1465420 ER PT J AU EPSTEIN, PN BOSCHERO, AC ATWATER, I CAI, XG OVERBEEK, PA AF EPSTEIN, PN BOSCHERO, AC ATWATER, I CAI, XG OVERBEEK, PA TI EXPRESSION OF YEAST HEXOKINASE IN PANCREATIC BETA-CELLS OF TRANSGENIC MICE REDUCES BLOOD-GLUCOSE, ENHANCES INSULIN-SECRETION, AND DECREASES DIABETES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLUCOKINASE GENE; ISLETS; MOLECULES AB It has been proposed that endogenous hexokinases of the pancreatic beta cell control the rate of glucose-stimulated insulin secretion and that genetic defects that reduce beta-cell hexokinase activity may lead to diabetes. To test these hypotheses, we have produced transgenic mice that have a 2-fold increase in hexokinase activity specific to the pancreatic beta cell. This increase was sufficient to significantly augment glucose-stimulated insulin secretion of isolated pancreatic islets, increase serum insulin levels in vivo, and lower the blood glucose levels of transgenic mice by 20-50% below control levels. Elevation of hexokinase activity also significantly reduced blood glucose levels of diabetic mice. These results confirm the role of beta-cell hexokinase activity in the regulation of insulin secretion and glucose homeostasis. They also provide strong support for the proposal that reductions in beta-cell hexokinase activity can produce diabetes. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,HOWARD HUGHES MED INST,HOUSTON,TX 77030. RP EPSTEIN, PN (reprint author), UNIV N DAKOTA,DEPT PHARMACOL & TOXICOL,GRAND FORKS,ND 58203, USA. RI Boschero, Antonio/O-7525-2014 OI Boschero, Antonio/0000-0003-3829-8570 NR 29 TC 82 Z9 82 U1 1 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1992 VL 89 IS 24 BP 12038 EP 12042 DI 10.1073/pnas.89.24.12038 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400082 PM 1465437 ER PT J AU ISHIBASHI, T BOTTARO, DP CHAN, A MIKI, T AARONSON, SA AF ISHIBASHI, T BOTTARO, DP CHAN, A MIKI, T AARONSON, SA TI EXPRESSION CLONING OF A HUMAN DUAL-SPECIFICITY PHOSPHATASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASES; CDC25 PROTEIN; CDNA LIBRARIES; HUMAN-PLACENTA; RECEPTOR; KINASE; SYSTEM; DEPHOSPHORYLATION; FAMILY; GENES AB Using an expression cloning strategy, we isolated a cDNA encoding a human protein-tyrosine-phosphatase. Bacteria expressing the kinase domain of the keratinocyte growth factor receptor (bek/fibroblast growth factor receptor 2) were infected with a fibroblast cDNA library in a phagemid prokaryotic expression vector and screened with a monoclonal anti-phosphotyrosine antibody. Among several clones showing decreased anti-phosphotyrosine recognition, one displayed phosphatase activity toward the kinase in vitro. The 4.1-kilobase cDNA encoded a deduced protein of 185 amino acids with limited sequence similarity to the vaccinia virus phosphatase VH1. The purified recombinant protein dephosphorylated several activated growth factor receptors, as well as serine-phosphorylated casein, in vitro. Both serine and tyrosine phosphatase activities were completely abolished by mutagenesis of a single cysteine residue conserved in VH1 and the VH1-related (VHR) human protein. These properties suggest that VHR is capable of regulating intracellular events mediated by both tyrosine and serine phosphorylation. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP AARONSON, SA (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 39 TC 178 Z9 180 U1 1 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1992 VL 89 IS 24 BP 12170 EP 12174 DI 10.1073/pnas.89.24.12170 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400109 PM 1281549 ER PT J AU KIRNBAUER, R BOOY, F CHENG, N LOWY, DR SCHILLER, JT AF KIRNBAUER, R BOOY, F CHENG, N LOWY, DR SCHILLER, JT TI PAPILLOMAVIRUS L1 MAJOR CAPSID PROTEIN SELF-ASSEMBLES INTO VIRUS-LIKE PARTICLES THAT ARE HIGHLY IMMUNOGENIC SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MONOCLONAL-ANTIBODIES; BACULOVIRUS; NEUTRALIZATION; VACCINATION; EXPRESSION; INFECTION; EPITOPES; CELLS; YEAST; L2 AB Infection by certain human papillomavirus types is regarded as the major risk factor in the development of cervical cancer, one of the most common cancers of women worldwide. Analysis of the immunogenic and structural features of papillomavirus virions has been hampered by the inability to efficiently propagate the viruses in cultured cells. For instance, it has not been established whether the major capsid protein L1 alone is sufficient for virus particle assembly. In addition, it is not known whether L1, L2 (the minor capsid protein), or both present the immunodominant epitopes required for induction of high-titer neutralizing antibodies. We have expressed the L1 major capsid proteins of bovine papillomavirus type 1 and human papillomavirus type 16 in insect cells via a baculovirus vector and analyzed their conformation and immunogenicity. The L1 proteins were expressed at high levels and assembled into structures that closely resembled papillomavirus virions. The self-assembled bovine papillomavirus L1, in contrast to L1 extracted from recombinant bacteria or denatured virions, also mimicked intact bovine papillomavirus virions in being able to induce high-titer neutralizing rabbit antisera. These results indicate that L1 protein has the intrinsic capacity to assemble into empty capsid-like structures whose immunogenicity is similar to infectious virions. This type of L1 preparation might be considered as a candidate for a serological test to measure antibodies to conformational virion epitopes and for a vaccine to prevent papillomavirus infection. C1 NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RP KIRNBAUER, R (reprint author), NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 616 Z9 654 U1 4 U2 47 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1992 VL 89 IS 24 BP 12180 EP 12184 DI 10.1073/pnas.89.24.12180 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400111 PM 1334560 ER PT J AU BUZY, J BRENNEMAN, DE PERT, CB MARTIN, A SALAZAR, A RUFF, MR AF BUZY, J BRENNEMAN, DE PERT, CB MARTIN, A SALAZAR, A RUFF, MR TI POTENT GP120-LIKE NEUROTOXIC ACTIVITY IN THE CEREBROSPINAL-FLUID OF HIV-INFECTED INDIVIDUALS IS BLOCKED BY PEPTIDE-T SO BRAIN RESEARCH LA English DT Article DE NEUROTOXICITY; GLYCOPROTEIN GP120; PEPTIDE-T; NEUROPATHOGENESIS; CEREBROSPINAL FLUID; ACQUIRED IMMUNODEFICIENCY DISEASE AIDS ID HUMAN IMMUNODEFICIENCY VIRUS; AIDS DEMENTIA COMPLEX; IMMUNE-DEFICIENCY SYNDROME; ENVELOPE PROTEIN GP120; RECEPTOR-BINDING; HTLV-III; MONONUCLEAR PHAGOCYTES; GLIAL-CELLS; BRAIN; SYSTEM AB The envelope protein of the human immunodeficiency virus (gp120) causes neuronal death in developing murine hippocampal cultures or rat retinal ganglion cells. In HIV-infected individuals, gp120 released from HIV-infected macrophages or other cells in the brain has been proposed as the etiology for the pathophysiology of AIDS central nervous system (CNS) disease by diffusing to act at a distance to cause damage and/or death to neighboring neurons. In this study, 28 cerebrospinal fluid (CSF) samples from HIV-infected individuals (79% were WR stage 1 and 2) and neurological disease controls were tested, blind to the investigator, for the presence of in vitro neuronal killing activity. Neurotoxic activity was detected with peak effects at a 1:10(5) dilution in CSF from 9/18 HIV-infected individuals and 1/10 neurological disease controls. Thus half of CSF from early stages of HIV disease are characterized by the presence of neurotoxic activity which is not present in control CSF (Fischers exact test, P < 0.05). The neuronal toxicity by patient CSF could be prevented by peptide T (1 nM). A monoclonal antibody to mouse CD4, RL.172, also attenuated or prevented CSF-induced neuronal killing in all four CSF samples tested. In addition, an antiserum to peptide T previously shown to bind gp120 and neutralize both infectivity and direct gp120 neurotoxicity, neutralized the CSF factor. gp120, or a modified small fragment, is suggested to be the responsible toxic molecular entity. These results may be relevant to the pathophysiology of HIV-related CNS disease and the mechanism by which peptide T causes improvements. C1 PEPTIDE DESIGN,GERMANTOWN,MD 20852. NICHHD,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,BETHESDA,MD 20889. RI martin, alex/B-6176-2009 NR 61 TC 47 Z9 47 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 11 PY 1992 VL 598 IS 1-2 BP 10 EP 18 DI 10.1016/0006-8993(92)90161-2 PG 9 WC Neurosciences SC Neurosciences & Neurology GA KE924 UT WOS:A1992KE92400002 PM 1486472 ER PT J AU HOSSAIN, MA MASSERANO, JM WEINER, N AF HOSSAIN, MA MASSERANO, JM WEINER, N TI COMPARATIVE EFFECTS OF ELECTROCONVULSIVE SHOCK AND HALOPERIDOL ON INVIVO TYROSINE HYDROXYLATION AND TETRAHYDROBIOPTERIN IN THE BRAIN OF RATS WITH 6-HYDROXYDOPAMINE LESIONS SO BRAIN RESEARCH LA English DT Article DE PARKINSONS DISEASE; 6-HYDROXYDOPAMINE; DOPAMINE; ELECTROCONVULSIVE SHOCK; HALOPERIDOL; TYROSINE HYDROXYLATION; DIHYDROXYPHENYLALANINE; TETRAHYDROBIOPTERIN ID GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE; DOPAMINE; STRIATUM; STRESS; COFACTOR; PARKINSONISM; RELEASE; CELLS AB We have evaluated the effects of electroconvulsive shock (ECS) and haloperidol treatment on the in vivo tyrosine hydroxylation rate and the tetrahydrobiopterin levels in the nigrostriatal system of 6-OHDA-lesioned rats. The rate of DOPA accumulation was significantly decreased by 96% in the ipsilateral striatum and by 50% in substantia nigra of the 6-OHDA-lesioned rats compared to the control activity of contralateral non-lesioned striatum and substantia nigra. The loss of total biopterin was found to be 75% and 50% in the ipsilateral striatum and substantia nigra, respectively. Following administration of haloperidol, the rate of DOPA accumulation increased significantly in the striatum and substantia nigra on the lesioned side compared to that in the vehicle treatment group. Application of ECS also significantly increased the rate of DOPA accumulation in the ipsilateral striatum and substantia nigra compared to that obtained in the non-shocked rats. The biopterin levels in the nigrostriatal system of 6-OHDA-lesioned rats were elevated significantly in the striatum after haloperidol treatment; in contrast the biopterin levels were unchanged in response to ECS. Our results show that both haloperidol and ECS significantly enhanced the rate of in vivo tyrosine hydroxylation in the striatum and substantia nigra of rats with greater than 90% lesions. These results suggest that the nigrostriatal system, although up-regulated following 6-OHDA lesions, still maintains the potential for further up-regulation of dopaminergic function in response to haloperidol and ECS treatment. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,BOX C-236,4200 E 9TH AVE,DENVER,CO 80262. ST ELIZABETH HOSP,NIMH,NEUROSCI BRANCH,WASHINGTON,DC 20032. FU NINDS NIH HHS [NS 09199] NR 32 TC 9 Z9 9 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 DEC 11 PY 1992 VL 598 IS 1-2 BP 121 EP 126 DI 10.1016/0006-8993(92)90175-9 PG 6 WC Neurosciences SC Neurosciences & Neurology GA KE924 UT WOS:A1992KE92400016 PM 1486474 ER PT J AU ANSON, RM CUTLER, R JOSEPH, JA YAMAGAMI, K ROTH, GS AF ANSON, RM CUTLER, R JOSEPH, JA YAMAGAMI, K ROTH, GS TI THE EFFECTS OF AGING ON MUSCARINIC RECEPTOR/G-PROTEIN COUPLING IN THE RAT HIPPOCAMPUS AND STRIATUM SO BRAIN RESEARCH LA English DT Note DE G-PROTEIN; AGING; STRIATUM; HIPPOCAMPUS; MUSCARINIC RECEPTOR; SIGNAL TRANSDUCTION; BINDING ASSAY; RECEPTOR AFFINITY ID NUCLEUS BASALIS MAGNOCELLULARIS; MEMORY DEFICITS; PHYSOSTIGMINE; DOPAMINE; SENESCENCE; BINDING; RELEASE; LESIONS; CELLS AB In the striatum and hippocampus, there is a loss of sensitivity to muscarinic agonists with age which has been traced to events early in the signal transduction pathway. Our laboratory has therefore focussed on investigations at this level. The current experiments investigate the effects of age on G-protein/receptor interactions by using competitive binding assays to measure the ability of GppNHp to decrease the proportion of receptors bound to G-proteins in the absence and the presence of added Mg2+. L-[H-3]Quinuclidinyl benzilate was used as a nonselective ligand and [H-3]pirenzepine as an M1 selective ligand. We find that: (1) muscarinic receptors and G-proteins in the striatum appear to become loosely coupled with age, with no change in Mg2+ sensitivity. (2) MI-receptor/G-protein complexes in the hippocampus display increased sensitivity to the presence of Mg2+ with age, with those from old but not young tissue requiring added Mg2+ in order to uncouple. This effect, however, may not be M1 specific. C1 NIA, GERONTOL RES CTR, MOLEC PHYSIOL & GENET SECT, BALTIMORE, MD 21224 USA. RI Yamagami, Keiji/E-9500-2012 NR 32 TC 27 Z9 27 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD DEC 11 PY 1992 VL 598 IS 1-2 BP 302 EP 306 PG 5 WC Neurosciences SC Neurosciences & Neurology GA KE924 UT WOS:A1992KE92400038 PM 1486490 ER PT J AU WAKISAKA, S KAJANDER, KC BENNETT, GJ AF WAKISAKA, S KAJANDER, KC BENNETT, GJ TI EFFECTS OF PERIPHERAL-NERVE INJURIES AND TISSUE INFLAMMATION ON THE LEVELS OF NEUROPEPTIDE-Y-LIKE IMMUNOREACTIVITY IN RAT PRIMARY AFFERENT NEURONS SO BRAIN RESEARCH LA English DT Note DE DORSAL ROOT GANGLION; HYPERALGESIA; NERVE INJURY; NEUROPATHIC PAIN; NEUROPEPTIDE-Y ID SPINAL-CORD; DORSAL HORN; SENSORY NEURONS; SCIATIC-NERVE; PAIN; MODEL; MONONEUROPATHY; NEUROPATHY; AXOTOMY; SECTION AB Changes in neuropeptide Y-like immunoreactivity (NPYir) in the rat L4 and L5 spinal cord and dorsal root ganglia (DRG) were examined after different sciatic nerve injuries (transection, loose ligation, and crush) and a localized, painful inflammation of the hind paw. Inflammation had no effect on NPYir. All the nerve injuries produced comparable increases in NPYir in ipsilateral laminae III-V axons and varicosities, and induction of NPYir in many DRG cells. Most NPYir DRG cells were medium to large (mean diameters: 40-45 mum); less than 2% of the cells had diameters of 25 mum or less. We conclude that the nerve injury-evoked increase in NPYir occurs mostly in the somata and intraspinal arbors of low-threshold mechanoreceptors; very few, if any, C-fiber afferents are involved. Nerve injury, rather than a painful condition, appears to be the stimulus for the induction of NPYir synthesis. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 30,ROOM B-20,BETHESDA,MD 20892. NR 22 TC 156 Z9 156 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 DEC 11 PY 1992 VL 598 IS 1-2 BP 349 EP 352 DI 10.1016/0006-8993(92)90206-O PG 4 WC Neurosciences SC Neurosciences & Neurology GA KE924 UT WOS:A1992KE92400047 PM 1486499 ER PT J AU EISENLOHR, LC BACIK, I BENNINK, JR BERNSTEIN, K YEWDELL, JW AF EISENLOHR, LC BACIK, I BENNINK, JR BERNSTEIN, K YEWDELL, JW TI EXPRESSION OF A MEMBRANE PROTEASE ENHANCES PRESENTATION OF ENDOGENOUS ANTIGENS TO MHC CLASS I-RESTRICTED LYMPHOCYTES-T SO CELL LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; ANGIOTENSIN-CONVERTING ENZYME; CELL-SURFACE EXPRESSION; ENDOPLASMIC-RETICULUM; BREFELDIN-A; INTRACELLULAR-TRANSPORT; INFLUENZA NUCLEOPROTEIN; VACCINIA VIRUS; RECOGNITION; MOLECULES AB We find that expression of the membrane dipeptidyl carboxypeptidase angiotensin-converting enzyme (ACE) enhances presentation of certain endogenously synthesized peptides to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes. ACE appears to function only in an intracellular secretory compartment of antigen-presenting cells. ACE-enhanced antigen presentation requires the expression of the putative antigenic peptide transporters, TAP1 and TAP2. These findings demonstrate that a protease can influence the processing of endogenously synthesized antigens and strongly suggest that longer peptides can be transported from the cytosol to a secretory compartment where trimming of antigenic peptides to the lengths preferred by MHC class I molecules can occur if the appropriate protease is present. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20906. EMORY UNIV,DEPT PATHOL,ATLANTA,GA 30322. RI yewdell, jyewdell@nih.gov/A-1702-2012; Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 47 TC 157 Z9 159 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 11 PY 1992 VL 71 IS 6 BP 963 EP 972 DI 10.1016/0092-8674(92)90392-P PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KB990 UT WOS:A1992KB99000009 PM 1333889 ER PT J AU SALVADORI, S BIANCHI, C LAZARUS, LH SCARANARI, V ATTILA, M TOMATIS, R AF SALVADORI, S BIANCHI, C LAZARUS, LH SCARANARI, V ATTILA, M TOMATIS, R TI PARA-SUBSTITUTED PHE3 DELTORPHIN ANALOGS - ENHANCED SELECTIVITY OF HALOGENATED DERIVATIVES FOR DELTA-OPIOID RECEPTOR-SITES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RAT-BRAIN MEMBRANES; OPIATE RECEPTORS; BINDING-SITES; HIGH-AFFINITY; VAS-DEFERENS; MU-RECEPTOR; DERMENKEPHALIN; DERMORPHIN; PEPTIDES; AGONIST AB The delta-selective opioid peptide deltorphin C(H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) (DEL C) was modified by para-substitution of Phe3 with halogens (F, Cl, Br, I), amino, or nitro groups. The bioactive potencies in peripheral tissues and brain receptor selectivities of these analogues depended upon the particular substituent; peptides containing halogen substituents exhibited the least disruptive effect. In the mouse vas deferens (MVD) bioassay, [p-ClPhe3]DEL C displayed equivalent bioactivities to DEL C; in combination with the guinea pig ileum (GPI) bioassay, [p-ClPhe3]DEL C and [p-BrPhe3]DEL C exhibited marked preference for delta sites (IC50GPI/IC50MVD = 11 250 and 6 363, respectively), which are approximately 4- and 2-fold greater than DEL C. In a receptor binding assay, none of the halogenated analogues had delta affinities (K(i)) exceeding that of DEL C; however, in terms of delta selectivity (K(i)mu/K(i)delta), [p-BrPhe3] DEL C was nearly twice as selective as DEL C, while [p-FPhe3]-DEL C was equivalent, and [p-IPhe3]DEL C only 25% less selective. The only correlation evident with the halogenated derivatives occurred between IC50GPI and K(i)mu (r = 0.814) rather than between delta receptor studies (MVD or K(i)delta); interestingly, IC50GPI also correlated with K' (r = 0.982). The p-amino or p-nitro substituents of Phe3 in DEL C and DEL B (= [Glu4]DEL C) were deleterious for bioactivity (MVD) (losses ranged from 400- to approximately 8 000-fold) and in receptor binding assays, where delta affinities decreased 140- to 840-fold and delta selectivities by 34- to 380-fold. p-Nitro-Phe3 was the most detrimental substitution for all the parameters measured for both deltorphins: the loss in MVD activity, however, was less with DEL B than with DEL C, which was the opposite for delta receptor affinity. C1 NIEHS,PEPTIDE NEUROCHEM SECT,INTEGRAT BIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. UNIV FERRARA,INST PHARMACOL,I-44100 FERRARA,ITALY. OI SALVADORI, Severo/0000-0002-8224-2358 NR 40 TC 28 Z9 28 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 11 PY 1992 VL 35 IS 25 BP 4651 EP 4657 DI 10.1021/jm00103a001 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KD458 UT WOS:A1992KD45800001 PM 1335080 ER PT J AU KIMES, AS WILSON, AA SCHEFFEL, U CAMPBELL, BG LONDON, ED AF KIMES, AS WILSON, AA SCHEFFEL, U CAMPBELL, BG LONDON, ED TI RADIOSYNTHESIS, CEREBRAL DISTRIBUTION, AND BINDING OF [I-125] 1-(P-IODOPHENYL)-3-(1-ADAMANTYL)GUANIDINE, A LIGAND FOR SIGMA-BINDING SITES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIPSYCHOTIC-DRUGS; GUINEA-PIG; AUTORADIOGRAPHIC LOCALIZATION; PHENCYCLIDINE RECEPTORS; OPIATE RECEPTORS; IMMUNE-SYSTEMS; HIGH-AFFINITY; MOUSE-BRAIN; RAT-BRAIN; HALOPERIDOL AB An analog of 1,3-di-o-tolylguanidine (DTG), [I-125]-labeled 1-(p-iodophenyl)-3-(1-adamantyl)-guanidine (PIPAG), was synthesized as a potential ligand for cerebral sigma binding sites. Data from in vitro binding experiments and in vivo experiments on brain distribution suggested that PIPAG binds to sigma binding sites with high affinity (K(d) in low nanomolar range) as determined by Scatchard analysis and relative potencies of sigma-specific drugs. Haloperidol had the highest potency to inhibit [I-125]PIPAG binding. It was followed by DTG, BMY 14802, and (+)-N-allylnormetazocine. Compounds with high affinities for dopamine receptors (but low affinity for sigma binding sites), for opioid receptors, for nicotinic acetylcholine receptors, and for phencyclidine receptors were ineffective inhibitors of [I-125]PIPAG binding. C1 JOHNS HOPKINS MED INST,DEPT RADIOL,DIV NUCL MED,BALTIMORE,MD 21287. RP KIMES, AS (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. RI Wilson, Alan/A-1788-2011 FU NCI NIH HHS [CA-32845]; NINDS NIH HHS [NS 15080] NR 48 TC 19 Z9 19 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 DEC 11 PY 1992 VL 35 IS 25 BP 4683 EP 4689 DI 10.1021/jm00103a005 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KD458 UT WOS:A1992KD45800005 PM 1469697 ER PT J AU DECOSTA, BR MATTSON, MV GEORGE, C LINDERS, JTM AF DECOSTA, BR MATTSON, MV GEORGE, C LINDERS, JTM TI SYNTHESIS, CONFIGURATION, AND ACTIVITY OF ISOMERIC 2-PHENYL-2-(N-PIPERIDINYL)BICYCLO[3.1.0]HEXANES AT PHENCYCLIDINE AND SIGMA-BINDING SITES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID D-ASPARTATE RECEPTOR; ANTICONVULSANT MK-801; RAT-BRAIN; ABSOLUTE-CONFIGURATION; POTENT; ANTAGONIST; MEMBRANES; COMPLEX; ANALOGS; INVIVO AB The novel semirigid derivatives (+)-cis-1-[2-phenyl-2-bicyclo[3.1.0]hexyl]piperidine [(+)-8], its enantiomer (-)-8, and (+/-)-trans-1-[2-phenyl-2-bicyclo[3.1.0]hexyl]piperidine [(+/-)-9] were synthesized as probes to investigate the mode of interaction of phencyclidine (PCP) with its binding site on the N-methyl-D-aspartate receptor complex. Each target compound was obtained in five steps starting from cyclopent-2-enone. (+)- and (-)-8 were obtained in greater than 98% optical purity through three recrystallizations from ethanol of the (S)-(+)- and (R)-(-)-mandelate salts of intermediate (+/-)-cis-2-phenyl-2-bicyclo[3.1.0]hexylamine([+/-)-16]. Crystallization of the (R)-(-)mandelate salt afforded (1R,2R,5S)-(-)-16, whereas the (S)-(+)-mandelate salt afforded (1S,2S,5R)-(+)-16; the absolute configuration was determined by single-crystal X-ray analysis of (-)-16.(R)-(-)-mandelate. Single-crystal X-ray analysis of (+/-)-9-picrate confirmed its trans configuration and provided conformational data. (+)- and (-)-8 and (+/-)-9 were examined for their ability to interact with PCP and sigma binding sites in vitro using [H-3]TCP and [H-3]pentazocine as radioligands. The binding was compared with that of PCP and contrasted with the rigid symmetrical phencyclidine derivatives cis- and trans-1-[3-phenyl-3-bicyclo[3.1.0]hexyl]piperidines (6 and 7). The results of the study indicated that the conformations of PCP represented by 6-9 are not optimal for potent interaction at either of these sites. Affinities ranged from 582 nM [(+/-)-9] to 29 000 nM [(+)-8] at PCP binding sites and from 1130 nM [(-)-8] to 16 300 nM (7) at sigma sites. In this assay, PCP exhibited affinities of 64.5 nM at PCP and 1090 nM at sigma sites. Qualitative correlation between the sigma and PCP binding data suggests some similarities between these binding sites. An axial phenyl and equatorial piperidine ring with the nitrogen lone pair of electrons antiperiplanar to the phenyl ring has been postulated as the receptor-active conformation of PCP-like ligands at the PCP binding site. Comparison of the binding data of 7-9 with that of the previously described methylcyclohexyl-PCP derivatives allowed its rationalization in terms of this model. It is likely that the lowered affinity in this bicyclo[3.1.0]hexane series is a consequence of nonoptimal geometry (pseudoequatorial phenyl or pseudoboat) for binding as opposed to the presence of steric bulk which proved deleterious in the methylcyclohexyl-PCP derivatives. C1 USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. RP DECOSTA, BR (reprint author), NIDDKD,MEDICINAL CHEM LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 57 TC 10 Z9 10 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 11 PY 1992 VL 35 IS 25 BP 4704 EP 4712 DI 10.1021/jm00103a008 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA KD458 UT WOS:A1992KD45800008 PM 1469699 ER PT J AU GONG, DW HASHIMOTO, S WADA, K ROEDER, RG NAKATANI, Y HORIKOSHI, M AF GONG, DW HASHIMOTO, S WADA, K ROEDER, RG NAKATANI, Y HORIKOSHI, M TI IMPERFECT CONSERVATION OF A SIGMA FACTOR-LIKE SUBREGION IN XENOPUS GENERAL TRANSCRIPTION FACTOR RAP30 SO NUCLEIC ACIDS RESEARCH LA English DT Note ID RNA POLYMERASE-II; PREINITIATION COMPLEX; INITIATION C1 ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. NIDCD,NEUROCHEM LAB,BETHESDA,MD 20892. UNIV TOKYO,INST APPL MICROBIOL,BUNKYO KU,TOKYO 113,JAPAN. NR 9 TC 8 Z9 9 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 DEC 11 PY 1992 VL 20 IS 23 BP 6414 EP 6414 DI 10.1093/nar/20.23.6414 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KF568 UT WOS:A1992KF56800043 PM 1475205 ER PT J AU MIZOGUCHI, H O'SHEA, JJ LONGO, DL LOEFFLER, CM MCVICAR, DW OCHOA, AC AF MIZOGUCHI, H O'SHEA, JJ LONGO, DL LOEFFLER, CM MCVICAR, DW OCHOA, AC TI ALTERATIONS IN SIGNAL TRANSDUCTION MOLECULES IN LYMPHOCYTES-T FROM TUMOR-BEARING MICE SO SCIENCE LA English DT Article ID CELL ANTIGEN RECEPTOR; PROTEIN-TYROSINE KINASE; ZETA-CHAIN; FC-RECEPTORS; ACTIVATION; COMPLEX; PHOSPHORYLATION; GENERATION; EXPRESSION; CD4 AB Impaired immune responses occur frequently in cancer patients or in tumor-bearing mice, but the mechanisms of the tumor-induced immune defects remain poorly understood. In an in vivo murine colon carcinoma model (MCA-38), animals bearing a tumor longer than 26 days develop CD8+ T cells with impaired cytotoxic function, decreased expression of the tumor necrosis factor-alpha and granzyme B genes, and decreased ability to mediate an antitumor response in vivo. T lymphocytes from tumor-bearing mice expressed T cell antigen receptors that contained low amounts of CD3gamma and completely lacked CD3zeta, which was replaced by the Fc(epsilon) gamma-chain. Expression of the tyrosine kinases p56lck and p59fyn was also reduced. These changes could be the basis of immune defects in tumor-bearing hosts. C1 NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, FREDERICK, MD 21701 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21701 USA. NCI, FREDERICK CANC RES & DEV CTR, EXPTL IMMUNOL LABS, FREDERICK, MD 21701 USA. RI McVicar, Daniel/G-1970-2015 FU NCI NIH HHS [N01-CO-74102] NR 45 TC 596 Z9 603 U1 1 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 11 PY 1992 VL 258 IS 5089 BP 1795 EP 1798 DI 10.1126/science.1465616 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KB964 UT WOS:A1992KB96400039 PM 1465616 ER PT J AU SETTE, A CEMAN, S KUBO, RT SAKAGUCHI, K APPELLA, E HUNT, DF DAVIS, TA MICHEL, H SHABANOWITZ, J RUDERSDORF, R GREY, HM DEMARS, R AF SETTE, A CEMAN, S KUBO, RT SAKAGUCHI, K APPELLA, E HUNT, DF DAVIS, TA MICHEL, H SHABANOWITZ, J RUDERSDORF, R GREY, HM DEMARS, R TI INVARIANT CHAIN PEPTIDES IN MOST HLA-DR MOLECULES OF AN ANTIGEN-PROCESSING MUTANT SO SCIENCE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I; BINDING SITE; T-CELLS; REGION; GENE; SPECIFICITY; MUTATIONS; MHC AB Class II major histocompatibility complexes bind peptides in an endosome-like compartment. When the class II null cell line 721.174 was transfected with class II DR3 genes, DR molecules were produced in normal amounts. However, the DR molecules were abnormally conformed and unstable because deletion of an antigen-processing gene had impaired intracellular formation of most class II-peptide complexes. Yet, 70 percent of the DR molecules still bore peptides, 80 percent of which were 21- to 24-amino acid fragments of the class II-associated invariant chain. These peptides were rare on DR3 from control cells. Thus, a defect in the main antigen-processing pathway revealed a process in which DR molecules bind long peptides derived from proteins present in the same compartment. C1 UNIV WISCONSIN,GENET LAB,MADISON,WI 53706. NCI,BETHESDA,MD 20892. UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22901. RP SETTE, A (reprint author), CYTEL,3525 JOHN HOPKINS COURT,SAN DIEGO,CA 92121, USA. RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 FU NIAID NIH HHS [AI15486, AI18634]; NIGMS NIH HHS [GM37537] NR 39 TC 207 Z9 207 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 11 PY 1992 VL 258 IS 5089 BP 1801 EP 1804 DI 10.1126/science.1465617 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KB964 UT WOS:A1992KB96400041 PM 1465617 ER PT J AU LANDS, WEM LIBELT, B MORRIS, A KRAMER, NC PREWITT, TE BOWEN, P SCHMEISSER, D DAVIDSON, MH BURNS, JH AF LANDS, WEM LIBELT, B MORRIS, A KRAMER, NC PREWITT, TE BOWEN, P SCHMEISSER, D DAVIDSON, MH BURNS, JH TI MAINTENANCE OF LOWER PROPORTIONS OF (N-6) EICOSANOID PRECURSORS IN PHOSPHOLIPIDS OF HUMAN PLASMA IN RESPONSE TO ADDED DIETARY (N-3) FATTY-ACIDS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE ARACHIDONIC ACID; LINOLEIC ACID; (N-3)FATTY ACID; EICOSANOID; EICOSAPENTAENOIC ACID; HIGHLY UNSATURATED FATTY ACID; PLASMA PHOSPHOLIPID; DIETARY FAT ID ARACHIDONIC-ACID; LINOLENIC ACID; LIPIDS; RATS; FISH; PROSTAGLANDINS; METABOLISM; OMEGA-3 AB Competition between the (n - 3) and (n - 6) types of highly unsaturated fatty acids can diminish the abundance of (n - 6) eicosanoid precursors in a tissue, which in turn can diminish the intensity of tissue responses that are mediated by (n - 6) eicosanoids. The mixture of 20- and 22-carbon highly unsaturated fatty acids maintained in the phospholipids of human plasma is related to the dietary intake of 18: 2 (n - 6) and 18: 3 (n - 3) by empirical hyperbolic equations in a manner very similar to the relationship reported for laboratory rats (Lands, W.E.M., Morris, A. and Libelt, B. (1990) Lipids 25, 505-516). Analytical results from volunteers ingesting self-selected diets showed an inter-individual variance for the proportion of (n - 6) eicosanoid precursors in the fatty acids of plasma phospholipids of about 5%, but the variance among multiple samples taken from the same individual throughout the day was less (about 3%), closer to the experimental variance of the analytical procedure (about 1%). The reproducibility of the results makes it likely that analysis of fatty-acid composition of plasma lipids from individuals will prove useful in estimating the diet-related tendency for severe thrombotic, arthritic or other disorders that are mediated by (n - 6) eicosanoids. Additional constants and terms were included in the equations to account for the effects of 20- and 22-carbon highly unsaturated (n - 3) fatty acids in the diet. A lower constant for the 20- and 22-carbon (n - 3) fatty acids compared to that for the 18-carbon (n - 3)fatty acid in decreasing the ability of dietary 18: 2 (n - 6) to maintain 20:4 (n - 6) in tissue lipids confirmed the greater competitive effectiveness of the more highly unsaturated n - 3 fatty acids in the elongation/desaturation process. Also, a lower constant for direct incorporation of 20-carbon fatty acids of the n - 6 vs. the n - 3 type indicated a greater competitive effectiveness of 20:4 (n - 6) relative to 20:5 (n - 3) in reesterification after release from tissue lipids. The equations may be used in reverse to estimate the dietary intakes of the (n - 3) and (n - 6) fatty acids by using the composition of the fatty acids that had been maintained in plasma lipids. C1 UNIV ILLINOIS,DEPT BIOL CHEM,CHICAGO,IL 60680. UNIV ILLINOIS,DEPT NUTR & MED DIETET,CHICAGO,IL 60680. CHICAGO CTR CLIN RES,CHICAGO,IL. RP LANDS, WEM (reprint author), NIAAA,DIV BASIC RES,5600 FISHERS LANE,RM 16C-06,ROCKVILLE,MD 20857, USA. RI Wilkinson, Stuart/C-2802-2013 NR 33 TC 164 Z9 168 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD DEC 10 PY 1992 VL 1180 IS 2 BP 147 EP 162 DI 10.1016/0925-4439(92)90063-S PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KC874 UT WOS:A1992KC87400005 PM 1463766 ER PT J AU MCKINNON, SJ WHITTENBURG, SL BROOKS, B AF MCKINNON, SJ WHITTENBURG, SL BROOKS, B TI NONEQUILIBRIUM MOLECULAR-DYNAMICS SIMULATION OF OXYGEN DIFFUSION THROUGH HEXADECANE MONOLAYERS WITH VARYING CONCENTRATIONS OF CHOLESTEROL SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; LIPID-PROTEIN INTERACTIONS; PROTON-TRANSFER REACTIONS; SODIUM OCTANOATE MICELLE; CONSISTENT FORCE FIELD; MONTE-CARLO; COMPUTER-SIMULATION; LIQUID-CRYSTALS; SPIN-LABEL; BILAYER MEMBRANES AB The effect of varying concentrations of cholesterol on the static properties of a hexadecane monolayer and on the diffusion rate of oxygen across the monolayer has been studied by using a novel application of nonequilibrium molecular dynamics. The results show an increased ordering of the hexadecane chains in the region of the monolayer near the added cholesterol with a general increase in monolayer thickness with increasing concentration of cholesterol. The calculation of the diffusion coefficients from the work required to pull oxygen through the monolayer by using a forcing potential suggests an enhanced diffusion rate of oxygen with added cholesterol and a decrease in the diffusion coefficient at higher cholesterol concentrations. C1 UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. NIH,BETHESDA,MD 20892. RP MCKINNON, SJ (reprint author), LOUISIANA STATE UNIV,CTR EYE,BATON ROUGE,LA 70803, USA. NR 118 TC 18 Z9 19 U1 2 U2 4 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 DEC 10 PY 1992 VL 96 IS 25 BP 10497 EP 10506 DI 10.1021/j100204a070 PG 10 WC Chemistry, Physical SC Chemistry GA KC007 UT WOS:A1992KC00700070 ER PT J AU DICKSON, B SPRENGER, F MORRISON, D HAFEN, E AF DICKSON, B SPRENGER, F MORRISON, D HAFEN, E TI RAF FUNCTIONS DOWNSTREAM OF RAS1 IN THE SEVENLESS SIGNAL TRANSDUCTION PATHWAY SO NATURE LA English DT Article ID RECEPTOR TYROSINE KINASE; DROSOPHILA-MELANOGASTER; PUTATIVE RECEPTOR; CELL FATE; PROTEIN; GENE; EYE; TORSO; REQUIREMENT; ACTIVATION AB SPECIFICATION of the R7 cell fate in the developing Drosophila eye requires activation of the Sevenless (Sev) receptor tyrosine kinase, located on the surface of the R7 precursor cell, by its interaction with the Boss protein, expressed on the surface of the neighbouring R8 cell1-3. Four genes that participate in the intracellular transmission of this signal have so far been identified and molecularly characterized: Ras1, Sos, Gap1 and sina (refs 4-8). The Drosophila homologue of the mammalian Raf-1 serine/threonine kinase, which has been implicated in signal transduction pathways activated by many receptor tyrosine kinases (reviewed in refs 9 and 10), is encoded by the raf locus (also known as l(1)polehole11, Draf-1 12 or Draf13). Here we show that the Drosophila Raf serine/threonine kinase also plays a crucial role in the R7 pathway: the response to Sev activity is dependent on raf function, and a constitutively activated Raf protein can induce R7 cell development in the absence of sev function. We also present genetic evidence suggesting that Raf acts downstream of Ras1 and upstream of Sina in this signal transduction cascade. C1 MAX PLANCK INST ENTWICKLUNGSBIOL,GENET ABT,W-7400 TUBINGEN,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP DICKSON, B (reprint author), UNIV ZURICH,INST ZOOL,WINTERTHORERSTR 190,CH-8057 ZURICH,SWITZERLAND. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 29 TC 275 Z9 276 U1 1 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 10 PY 1992 VL 360 IS 6404 BP 600 EP 603 DI 10.1038/360600a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KB959 UT WOS:A1992KB95900090 PM 1461284 ER PT J AU MILLER, BA FEUER, EJ HANKEY, BF AF MILLER, BA FEUER, EJ HANKEY, BF TI BREAST-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP MILLER, BA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 4 Z9 4 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 DEC 10 PY 1992 VL 327 IS 24 BP 1756 EP 1757 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA KA897 UT WOS:A1992KA89700015 PM 1435922 ER PT J AU OREN, DA WEHR, TA AF OREN, DA WEHR, TA TI HYPERNYCTOHEMERAL SYNDROME AFTER CHRONOTHERAPY FOR DELAYED SLEEP PHASE SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP OREN, DA (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 5 TC 31 Z9 31 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 DEC 10 PY 1992 VL 327 IS 24 BP 1762 EP 1762 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KA897 UT WOS:A1992KA89700027 PM 1435929 ER PT J AU GORDIS, E ALEXANDER, D AF GORDIS, E ALEXANDER, D TI BASIC RESEARCH SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 NICHHD, BETHESDA, MD 20892 USA. RP GORDIS, E (reprint author), NIAAA, ROCKVILLE, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 9 PY 1992 VL 268 IS 22 BP 3183 EP 3183 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KA654 UT WOS:A1992KA65400006 ER PT J AU GORDIS, E ALEXANDER, D AF GORDIS, E ALEXANDER, D TI THE CONTINUUM OF ARBD SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 NICHHD, BETHESDA, MD 20892 USA. RP GORDIS, E (reprint author), NIAAA, ROCKVILLE, MD 20852 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 9 PY 1992 VL 268 IS 22 BP 3183 EP 3183 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KA654 UT WOS:A1992KA65400005 ER PT J AU GORDIS, E ALEXANDER, D AF GORDIS, E ALEXANDER, D TI PROGRESS TOWARD PREVENTING AND UNDERSTANDING ALCOHOL-INDUCED FETAL INJURY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 NICHHD, BETHESDA, MD 20892 USA. RP GORDIS, E (reprint author), NIAAA, ROCKVILLE, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 9 PY 1992 VL 268 IS 22 BP 3183 EP 3183 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KA654 UT WOS:A1992KA65400004 ER PT J AU CHEN, YCJ GUO, YL HSU, CC ROGAN, WJ AF CHEN, YCJ GUO, YL HSU, CC ROGAN, WJ TI COGNITIVE-DEVELOPMENT OF YU-CHENG (OIL DISEASE) CHILDREN PRENATALLY EXPOSED TO HEAT-DEGRADED PCBS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POLYCHLORINATED-BIPHENYLS PCBS; BIRTH-DEFECTS; DIBENZOFURANS; CONTAMINANTS; DIOXINS; TAIWAN; BLOOD AB Objective.-To compare the cognitive development in Taiwanese children who had been exposed prenatally to high levels of heat-degraded polychlorinated biphenyls (PCBs) with control children who were exposed to background levels. The disorder was called Yu-Cheng, "oil disease," in Taiwan. Design.-Matched-pair cohort study. Setting.-Communities in central Taiwan in which there had been a cooking-oil contamination and mass poisoning by heat-degraded PCBs in 1978 through 1979. Participants.-One hundred eighteen children born between June 1978 and March 1985 during or after their mothers' consumption of contaminated rice oil; 118 children matched for age, sex, neighborhood, maternal age, and parental education and occupational class; and 15 older siblings of exposed children, born before the poisoning. Main Outcome Measures.-Cognitive development measured from 1985 through 1990 using the Chinese versions of the Stanford-Binet test and the Wechsler Intelligence Scale for Children, Revised. Results.-The exposed children scored approximately 5 points lower on the Stanford-Binet test at the ages of 4 and 5 years and approximately 5 points lower on the Wechsler Intelligence Scale for Children, Revised, at the ages of 6 and 7 years. Children born up to 6 years after their mothers' exposure were as affected as children born within a year or two after exposure when examined at 6 and 7 years of age. Older siblings resembled the control children. Conclusion.-Children prenatally exposed to heat-degraded PCBs had poorer cognitive development than their matched controls. The effect persisted in the children up to the age of 7 years, and children born long after the exposure were still affected. C1 NATL CHENG KUNG UNIV,COLL MED,DEPT ENVIRONM HLTH,TAINAN,TAIWAN. NIEHS,RES TRIANGLE PK,NC 27709. RP CHEN, YCJ (reprint author), NATL CHENG KUNG UNIV,COLL MED,DEPT PSYCHIAT,138 SHENG LI RD,TAINAN 70428,TAIWAN. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 36 TC 192 Z9 200 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 9 PY 1992 VL 268 IS 22 BP 3213 EP 3218 DI 10.1001/jama.268.22.3213 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA KA654 UT WOS:A1992KA65400027 PM 1433761 ER PT J AU DALAKAS, MC AF DALAKAS, MC TI ELEVATED CREATINE-KINASE LEVEL IN POSTPOLIO SYNDROME SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID NEUROMUSCULAR SYMPTOMS RP DALAKAS, MC (reprint author), NIH,BETHESDA,MD 20892, USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 9 PY 1992 VL 268 IS 22 BP 3248 EP 3248 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KA654 UT WOS:A1992KA65400036 PM 1433769 ER PT J AU ZOLKIEWSKI, M GINSBURG, A AF ZOLKIEWSKI, M GINSBURG, A TI THERMODYNAMIC EFFECTS OF ACTIVE-SITE LIGANDS ON THE REVERSIBLE, PARTIAL UNFOLDING OF DODECAMERIC GLUTAMINE-SYNTHETASE FROM ESCHERICHIA-COLI - CALORIMETRIC STUDIES SO BIOCHEMISTRY LA English DT Article ID STATISTICAL MECHANICAL DECONVOLUTION; L-METHIONINE SULFOXIMINE; SCANNING CALORIMETRY; THERMAL TRANSITIONS; BINDING; SUBUNIT; PROTEIN; MACROMOLECULES; ADENYLYLATION; DOMAINS AB Dodecameric glutamine synthetase (GS) from Escherichia coli undergoes reversible, thermally induced partial unfolding without subunit dissociation. A single endotherm for Mn-GS (+/-active-site ligands) in the presence of 1 mM free Mn2+ and 100 mM KCl at pH 7 is observed by differential scanning calorimetry (DSC). Previous deconvolutions of DSC data for Mn.GS showed only two two-state transitions (with similar t(m) values; 51.6 +/- 2-degrees-C), and indicated that cooperative interactions link partial unfolding reactions of all subunits within the Mn.enzyme dodecamer [Ginsburg, A., & Zolkiewski, M. (1991) Biochemistry 30, 9421]. A net uptake of 8.0 equiv of H+ by Mn.GS occurs during partial unfolding, as determined in the present DSC experiments conducted with four buffers having different heats of protonation at 50-degrees-C. These data gave a value of 176 +/- 12 kcal (mol of dodecamer)-1 for DELTAH(cal) corrected for buffer protonation. L-Glutamine and L-Met-(SR)-sulfoximine stabilize the Mn.GS dodecamer through the free energies of ligand binding, and these were shown to be partially and totally released, respectively, from the 12 active sites at high temperature. Ligand effects on T(m) values from DSC were similar to those from spectral measurements of Trp and Tyr exposures in two subunit domains. Effects of varying [ADP] on DSC profiles of Mn.GS were complex; T(m) is increased by low [ADP] and decreased by > 100 muM free ADP. This is due to the exposure of an additional low-affinity ADP binding site per GS subunit at high temperature with log K1' = 4.3 and log K2' = 3.6 at 60-degrees-C relative to log K'= 5.5 for ADP binding at 30-degrees-C, as determined by isothermal calorimetric and fluorescence titrations. Moreover, DELTAH(cal) at >27% saturation with ADP (corrected for ADP binding/dissociation) is approximately 80-100 kcal/mol more than in the absence of ligands. Changes in domain interactions could result from ADP bridging subunit contacts in the dodecamer. Each of the active-site ligands investigated here produces different effects on DSC profiles without uncoupling the extremely cooperative, partial unfolding reactions in the Mn.GS dodecamer. C1 NHLBI,BIOCHEM LAB,PROT CHEM SECT,BLDG 3,ROOM 208,BETHESDA,MD 20892. NR 37 TC 16 Z9 16 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 DEC 8 PY 1992 VL 31 IS 48 BP 11991 EP 12000 DI 10.1021/bi00163a006 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB737 UT WOS:A1992KB73700006 PM 1360813 ER PT J AU BAGDY, G KALOGERAS, KT SZEMEREDI, K AF BAGDY, G KALOGERAS, KT SZEMEREDI, K TI EFFECT OF 5-HT(1C) AND 5-HT(2) RECEPTOR STIMULATION ON EXCESSIVE GROOMING, PENILE ERECTION AND PLASMA OXYTOCIN CONCENTRATIONS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE 5-HT (5-HYDROXYTRYPTAMINE, SEROTONIN); EXCESSIVE GROOMING; PENILE ERECTION; OXYTOCIN CONCENTRATION (PLASMA); 5-HT(1C)RECEPTORS; 5-HT(2)RECEPTORS; M-CPP (1-(3-CHLOROPHENYL)PIPERAZINE); DOI (1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE) ID MALE-RATS; M-CHLOROPHENYLPIPERAZINE; SEROTONIN AGONISTS; 5-HT1C RECEPTORS; CONSCIOUS RATS; PITUITARY; RESPONSES; BEHAVIOR; PHARMACOLOGY; APOMORPHINE AB Serotonin (5-HT) receptor agonist-induced excessive grooming, penile erection and oxytocin secretion were studied in chronically cannulated freely moving rats. The 5-HT1C receptor agonist, m-chlorophenylpiperazine (m-CPP), which also binds to other 5-HT receptors, produced dose-dependent excessive grooming, penile erection and increases in circulating oxytocin concentrations. Maximal responses for excessive grooming and penile erection occurred at 0.3-0.6 mg/kg i.v. m-CPP. Higher doses (0.9-2.5 mg/kg i.v.) caused further increases in oxytocin concentrations, but attenuated both behavioral responses. All three responses to m-CPP (0.6 mg/kg) were attenuated by antagonists with high affinity for the 5-HT1C receptor site (mianserin, LY-53857 and metergoline), but not by the 5-HT2 receptor antagonist ketanserin. The 5-HT2/5-HT1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), increased plasma oxytocin concentrations only. After ketanserin pretreatment, DOI caused penile erection and diminished the oxytocin response. All responses to DOI were blocked completely by pretreatment with LY-53857 plus ketanserin. Excessive grooming and penile erection showed significant bimodal correlations with the oxytocin response. These data suggest that stimulation of 5-HT1C receptors induces excessive grooming, penile erection and increased oxytocin secretion. Stimulation of 5-HT2 receptors causes a further increase in plasma oxytocin concentration, but inhibits both behavioral responses. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. EGIS PHARMACEUT,DEPT PHARMACOL,BUDAPEST,HUNGARY. RP BAGDY, G (reprint author), NATL INST PSYCHIAT & NEUROL,EXPTL MED LAB,HUVOSVOLGYI 116,BUDAPEST 27,POB 1,H-1281 BUDAPEST,HUNGARY. OI Bagdy, Gyorgy/0000-0001-8141-3410 NR 27 TC 70 Z9 70 U1 0 U2 3 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 DEC 8 PY 1992 VL 229 IS 1 BP 9 EP 14 DI 10.1016/0014-2999(92)90279-D PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KD823 UT WOS:A1992KD82300002 PM 1473565 ER PT J AU FUJII, H SHINYA, E SHIMADA, T AF FUJII, H SHINYA, E SHIMADA, T TI A GC BOX IN THE BIDIRECTIONAL PROMOTER IS ESSENTIAL FOR EXPRESSION OF THE HUMAN DIHYDROFOLATE-REDUCTASE AND MISMATCH REPAIR PROTEIN-1 GENES SO FEBS LETTERS LA English DT Article DE DIHYDROFOLATE REDUCTASE; BIDIRECTIONAL PROMOTER; LUCIFERASE; TRANSCRIPTION CONTROL; GC BOX; TATA BOX ID MAMMALIAN-CELLS; TRANSCRIPTION; REGION; UPSTREAM; SEQUENCE; ELEMENT; BINDING; INITIATION; ACTIVATION; COLLAGEN AB The human dihydrofolate reductase and mismatch repair protein 1 genes are organized in a head-to-head configuration separated by an 88 base-pair segment and directed by a bidirectional promoter. In vivo transient assays of the site directed mutant promoters using firefly luciferase as a reporter showed that an AT-rich sequence, ACAAATA, in the GC-rich promoter sequence is not required for transcription. However, two out of four GC boxes were shown to function as bidirectional positive regulatory elements. Among them, a GC box at the midpoint of the region between the two initiation sites is essential for supporting minimal bidirectional activity. C1 NIPPON MED COLL,DEPT BIOCHEM & MOLEC BIOL,1-1-5 SENDAGI,BUNKYO KU,TOKYO 113,JAPAN. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 23 TC 23 Z9 23 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 DEC 7 PY 1992 VL 314 IS 1 BP 33 EP 36 DI 10.1016/0014-5793(92)81455-U PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA KB081 UT WOS:A1992KB08100010 PM 1451803 ER PT J AU KOSUGI, S OKAJIMA, F BAN, T HIDAKA, A SHENKER, A KOHN, LD AF KOSUGI, S OKAJIMA, F BAN, T HIDAKA, A SHENKER, A KOHN, LD TI MUTATION OF ALANINE 623 IN THE 3RD CYTOPLASMIC LOOP OF THE RAT THYROTROPIN (TSH) RECEPTOR RESULTS IN A LOSS IN THE PHOSPHOINOSITIDE BUT NOT CAMP SIGNAL INDUCED BY TSH AND RECEPTOR AUTOANTIBODIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SITE-DIRECTED MUTAGENESIS; THYROID-CELLS; CYCLIC-AMP; STIMULATION; ASSIGNMENT; DOMAINS; BINDING; REGIONS; GENE AB Thyrotropin (TSH) and IgG preparations from patients with Graves' disease increase inositol phosphate as well as cAMP formation in Cos-7 cells transfected with rat TSH receptor cDNA. Mutation of alanine 623 in the carboxyl end of the third cytoplasmic loop of the TSH receptor, to lysine or glutamic acid, results in the loss of TSH- and Graves' IgG-stimulated inositol phosphate formation but not in stimulated cAMP formation. There is no effect of the mutations on basal or P2-purinergic receptor-mediated inositol phosphate formation. The mutations do not affect transfection efficiency or the synthesis, processing, or membrane integration of the receptor, as evidenced by the unchanged amount and composition of the TSH receptor forms on Western blots of membranes from transfected cells. The mutations increase the affinity of the TSH receptor for [I-125]TSH and decrease B(max); however, cells with an equivalently decreased B(max) as a result of transfection with lower levels of wild type receptor do not lose either TSH-induced inositol phosphate formation or cAMP signaling activity. Thus, in addition to discriminating between ligand-induced phosphatidylinositol bisphosphate and cAMP signals, the mutation appears to cause an altered receptor conformation which affects ligand binding to its large extracellular domain. C1 NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. RP KOSUGI, S (reprint author), NIDDKD,CELL REGULAT SECT,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. NR 23 TC 139 Z9 141 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1992 VL 267 IS 34 BP 24153 EP 24156 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA263 UT WOS:A1992KA26300002 PM 1332945 ER PT J AU COOK, JC CHOCK, PB AF COOK, JC CHOCK, PB TI ISOFORMS OF MAMMALIAN UBIQUITIN-ACTIVATING ENZYME SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE Y-CHROMOSOME; L-CELL DEFECT; ELECTROPHORETIC TRANSFER; DEPENDENT PROTEOLYSIS; GEL-ELECTROPHORESIS; POLYACRYLAMIDE GELS; CONJUGATING ENZYME; MOLECULAR-CLONING; DNA-REPLICATION; GENE AB Ubiquitin-activating enzyme,"E1," is the first enzyme in the pathway leading to formation of ubiquitin-protein conjugates and represents a potential target for regulation in the metabolic control of the conjugation reaction. Antiserum raised against human E1 recognizes two immunoreactive proteins in extracts from several human cell lines and animal tissues. We have characterized these two immunoreactive proteins in HeLa cells and present evidence that they are isoforms of E1. We have designated these isoforms as "E1(110 kDa)" and "E1(117 kDa)" to reflect their apparent molecular masses determined from SDS-polyacrylamide gel electrophoresis. These two immunoreactive proteins are immunologically similar, have nearly identical peptide maps, and comigrate with enzymatic activity characteristic of E1 in native polyacrylamide gel electrophoretic separations. Pulse-labeling experiments reveal that both isoforms are long-lived in vivo with degradation rates which are inconsistent with a proenzyme/enzyme model. Furthermore, their rates of degradation, which vary depending on the cell line studied, are kinetically distinguishable in contact-inhibited human lung fibroblasts. This work represents the first demonstration of E1 isoforms in a non-plant species and carries important implications for studies of the regulatory mechanisms controlling ubiquitin conjugation. C1 NHLBI,BIOCHEM LAB,METAB REGULAT,BLDG 3,RM 202,BETHESDA,MD 20892. NR 53 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1992 VL 267 IS 34 BP 24315 EP 24321 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA263 UT WOS:A1992KA26300029 PM 1447181 ER PT J AU SMYTH, MJ WILTROUT, T TRAPANI, JA OTTAWAY, KS SOWDER, R HENDERSON, LE KAM, CM POWERS, JC YOUNG, HA SAYERS, TJ AF SMYTH, MJ WILTROUT, T TRAPANI, JA OTTAWAY, KS SOWDER, R HENDERSON, LE KAM, CM POWERS, JC YOUNG, HA SAYERS, TJ TI PURIFICATION AND CLONING OF A NOVEL SERINE PROTEASE, RNK-MET-1, FROM THE GRANULES OF A RAT NATURAL-KILLER-CELL LEUKEMIA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TOXIC LYMPHOCYTE-T; PORCINE PANCREATIC ELASTASE; CYTOLYTIC LYMPHOCYTES; CYTOPLASMIC GRANULES; SUBSTRATE-SPECIFICITY; DNA FRAGMENTATION; GENE-EXPRESSION; HUMAN-LEUKOCYTE; MEDIATED LYSIS; CYTO-TOXICITY AB We have purified a 30-kDa serine protease (designated RNK-Met-1) from the granules of the rat large granular lymphocyte leukemia cell line (RNK-16) that hydrolytically cleaves model peptide substrates after methionine, leucine, and norleucine (Met-ase activity). Utilizing molecular sieve chromatography, heparin-agarose, chromatography, and reverse-phase high pressure liquid chromatography, RNK-Met-1 was purified to homogeneity and 25 NH2-terminal amino acids were sequenced. By using the polymerase chain reaction, oligonucleotide primers derived from amino acids at position 14-25 and from a downstream active site conserved in other serine protease genes were used to generate a 534-base pair cDNA clone encoding a novel serine protease from RNK-16 mRNA. This cDNA clone was used to isolate a full-length 867-base pair RNK-Met-1 cDNA from an RNK-16 lambda-gt11 library. The open reading frame predicts a mature protein of 238 amino acids with two potential sites for N-linked glycosylation. The cDNA also encodes a leader peptide of at least 20 amino acids. The characteristic lIe-lIe-Gly-Gly amino acids of the NH2 terminus and the His, Asp, and Ser residues that form the catalytic triad of serine proteases were both conserved. The amino acid sequence has less than 45% identity with any other member of the serine protease family, indicating that RNK-Met-I is distinct and may itself represent a new subfamily of serine proteases. Northern blot analysis of total cellular RNA detected a single 0.9-kilobase mRNA in the in vitro and in vivo variants of RNK-16 and in spleen-derived plastic-adherent rat lymphokine-activated killer cells. RNK-Met-1 mRNA was not detectable in freshly isolated rat splenocytes, thymocytes, brain, colon, and liver or activated nonadherent rat splenocytes and thymocytes. These data indicate that RNK-Met-1 is a serine protease with unique activity that is expressed in the granules of large granular lymphocytes. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CLIN SERV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE DEV PROGRAM,FREDERICK,MD 21702. GEORGIA INST TECHNOL,SCH CHEM & BIOCHEM,ATLANTA,GA 30332. RP SMYTH, MJ (reprint author), AUSTIN HOSP,AUSTIN RES INST,CELLULAR CYTOX LAB,HEIDELBERG,VIC 3084,AUSTRALIA. RI Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU NCI NIH HHS [CM42212, N01-CO-74102]; NHLBI NIH HHS [HL29307] NR 65 TC 62 Z9 63 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1992 VL 267 IS 34 BP 24418 EP 24425 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA263 UT WOS:A1992KA26300045 PM 1447189 ER PT J AU LEE, FJS MOSS, J VAUGHAN, M AF LEE, FJS MOSS, J VAUGHAN, M TI HUMAN AND GIARDIA ADP-RIBOSYLATION FACTORS (ARFS) COMPLEMENT ARF FUNCTION IN SACCHAROMYCES-CEREVISIAE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING-PROTEINS; CHOLERA-TOXIN; ADENYLATE-CYCLASE; GENE DISRUPTION; MESSENGER-RNA; YEAST; GTP; EXPRESSION; ACTIVATORS; SEQUENCES AB ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro. ARFs are highly conserved, ubiquitously expressed in eukaryotic cells and appear to be involved in vesicular protein transport. The two yeast ARFs are >60% identical to mammalian ARFs and are essential for cell viability (Stearns, T., Kahn, R. A., Botstein, D., and Hoyt, M. A. (1990) Mol. Cell. Biol. 10, 6690-6699). Although the two yeast ARF proteins are 96% identical in amino acid sequence, the yeast ARF1 gene is constitutively expressed, whereas the ARF2 gene is repressed by glucose. Human ARF5 and ARF6 and a Giardia ARF differ substantially in size and amino acid identity from other mammalian and eukaryotic ARFs but will, as befits their designation, activate cholera toxin. Expression of human ARF5, ARF6, or Giardia ARF cDNA rescued the lethal yeast ARF double mutant (arf1, arf2). Strains rescued by human ARF5, ARF6, or Giardia ARF grew much more slowly than wild-type yeast or strains rescued with yeast ARF1. We infer from the impaired growth of these rescued strains that the homologous ARFs may have specific targeting information that does not interact effectively or efficiently with the yeast protein membrane trafficking system. RP LEE, FJS (reprint author), NHLBI,CELLULAR METAB LAB,RM 5N-307,BLDG 10,BETHESDA,MD 20892, USA. OI LEE, FANG-JEN/0000-0002-2167-2426 NR 33 TC 35 Z9 36 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 DEC 5 PY 1992 VL 267 IS 34 BP 24441 EP 24445 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA263 UT WOS:A1992KA26300048 PM 1447192 ER PT J AU BARSONY, J MCKOY, W AF BARSONY, J MCKOY, W TI MOLYBDATE INCREASES INTRACELLULAR 3',5'-GUANOSINE CYCLIC MONOPHOSPHATE AND STABILIZES VITAMIN-D RECEPTOR ASSOCIATION WITH TUBULIN-CONTAINING FILAMENTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN GINGIVAL FIBROBLASTS; GUANYLATE-CYCLASE ACTIVITY; HEAT-SHOCK PROTEIN; GLUCOCORTICOID-RECEPTOR; CYTOPLASMIC MICROTUBULES; CILIARY MOTILITY; DNA-BINDING; CELLS; COMPLEX; CGMP AB With a recently developed method we detected rapid and sequential reorganization of vitamin D receptors (VDR), including their temporary association with fibers, and we showed that calcitriol induces cGMP accumulation around reorganizing VDRs. In this report we first identified the VDR-associated fibers as microtubules: they showed immunoreactivity with tubulin antisera and were sensitive to tubulin-disruptive agents. Tubulin-disruptive agents also prevented calcitriol-induced alignment and intranuclear accumulation of VDR and cGMP, but did not prevent the initial cGMP accumulation in the cytoplasm. Then we studied the effect of molybdate on VDR reorganization and on cGMP accumulation. Sodium molybdate inhibits steroid receptor transformation into a DNA binding form through interaction with the steroid binding region of the receptor. The mechanism of molybdate effect on steroid receptors is not well understood and the interaction of molybdate with guanylate cyclase has not been investigated. We found in cells pretreated with molybdate that the addition of calcitriol resulted in a prolonged and accentuated association of VDR and cGMP with the microtubules. Furthermore, both immunocytology and radioimmunoassay demonstrated that molybdate is a highly potent inducer of guanylate cyclase. Neither calcitriol nor molybdate effect on guanylate cyclase were prevented by methylene blue pretreatment, suggesting that they activate particulate guanylate cyclase. Pretreatment of cells with dibutyryl-cGMP mimicked molybdate effect on VDR reorganization. The effect of molybdate on cGMP may participate in molybdate stabilization of steroid receptors. We suggest that rapid cGMP accumulation after steroid exposure plays a role in facilitation of intracellular transport of the steroid receptor through interaction with microtubules. RP BARSONY, J (reprint author), NIDDKD,MINERAL METAB SECT,BETHESDA,MD 20892, USA. NR 47 TC 49 Z9 49 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 DEC 5 PY 1992 VL 267 IS 34 BP 24457 EP 24465 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA263 UT WOS:A1992KA26300050 PM 1280259 ER PT J AU TANG, CK CHIN, J HARFORD, JB KLAUSNER, RD ROUAULT, TA AF TANG, CK CHIN, J HARFORD, JB KLAUSNER, RD ROUAULT, TA TI IRON REGULATES THE ACTIVITY OF THE IRON-RESPONSIVE ELEMENT BINDING-PROTEIN WITHOUT CHANGING ITS RATE OF SYNTHESIS OR DEGRADATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FERRITIN MESSENGER-RNA; AFFINITY PURIFICATION; UNTRANSLATED REGION; IRE-BP; ACONITASE; TRANSLATION; EXPRESSION; REPRESSOR; MECHANISM; SEQUENCE AB The iron-responsive element binding protein (IRE-BP) interacts with specific sequence/structure motifs (iron-responsive elements) within the mRNAs encoding ferritin and the transferrin receptor and thereby post-transcriptionally regulates the expression of these two proteins involved in cellular iron homeostasis. The activity of the IRE-BP is itself regulated by iron such that when cells are treated with an iron source, the RNA binding activity is decreased. The expression of recombinant human IRE-BP in murine cells has been examined as have the expressions of the endogenous IRE-BP of both human and rabbit cells. In all cases, iron down-modulated the RNA binding activity of the IRE-BP, but in no instance was this decrease in activity accompanied by a decrease in the level of the protein as judged by quantitative Western blots. Moreover, the rate of synthesis of the IRE-BP and its rate of degradation have been found to be unaltered by iron manipulation of cells in culture. Consistent with IRE-BP regulation occurring post-translationally, the iron regulation of its activity was found to be unaffected by cycloheximide. These data are discussed in terms of a model of IRE-BP regulation involving the modification of the protein's iron-sulfur center. RP TANG, CK (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 29 TC 61 Z9 61 U1 1 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 DEC 5 PY 1992 VL 267 IS 34 BP 24466 EP 24470 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA263 UT WOS:A1992KA26300051 PM 1447194 ER PT J AU SAKAGUCHI, K AF SAKAGUCHI, K TI ACIDIC FIBROBLAST GROWTH-FACTOR AUTOCRINE SYSTEM AS A MEDIATOR OF CALCIUM-REGULATED PARATHYROID CELL-GROWTH SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBENDOTHELIAL EXTRACELLULAR-MATRIX; HEPARAN-SULFATE PROTEOGLYCAN; CAPILLARY ENDOTHELIAL-CELLS; HIGH-AFFINITY RECEPTOR; NUCLEOTIDE-SEQUENCE; PRIMARY CULTURES; BOVINE; LINE; BINDING; PROLIFERATION AB Both parathyroid hormone secretion and cell growth are negatively regulated by extracellular calcium in parathyroid cells. The mechanism of growth regulation by calcium has been unknown. Previously, we reported that clonal parathyroid cells (PT-r cells) bear two high affinity receptors for acidic fibroblast growth factor (aFGF) and that at least a subpopulation of the receptors with a higher molecular mass carries heparan sulfate (HS) glycosaminoglycan chains which give the receptor higher affinity (Sakaguchi, K., Yanagishita, M., Takeuchi, Y., and Aurbach, G. D. (1991) J. Biol. Chem. 266, 7270-7278). Here, I have found that the parathyroid cells expressed aFGF and that aFGF receptors with lower affinity apparently translocated in response to changing extracellular calcium concentrations. Expression of both aFGF mRNA and peptide was suppressed by calcium. Cells had more ligand-accessible receptors on the cell surface at lower calcium concentrations. This apparent translocation was temperature-dependent but independent of de novo protein synthesis. Heparin or HS glycosaminoglycans are a prerequisite for the FGF receptor encoded by flg gene to bind basic FGF (Yayon, A., Klagsbrun, M., Esko, J. D., Leder, P., and Ornitz, D. M. (1991) Cell 64, 841-848). In PT-r cells, major cellular HS proteoglycans redistribute between intracellular and extracellular compartments with more HS proteoglycans expressed on the cell surface at lower calcium concentrations (Takeuchi, Y., Sakaguchi, K., Yanagishita, M., Aurbach, G. D., and Hascall, V. C. (1990) J. Biol. Chem. 265, 13661-13668). However, this redistribution of HS proteoglycans cannot explain the difference in bindability of radiolabeled aFGF to its receptors in different calcium concentrations, since addition of heparin did not change the binding of radiolabeled aFGF to the receptors either at high or low calcium conditions. In concordance with the apparent translocation of aFGF receptors, thymidine incorporation was stimulated by decreasing extracellular calcium concentrations with further stimulation by added aFGF. Anti-aFGF antibody inhibited thymidine incorporation by more than 32% in the cells exposed to 0.05 mM Ca2+ shortly before adding [H-3]thymidine, whereas the incorporation was not significantly affected by the antibody at 0.7 mM Ca2+. Cell growth was also stimulated by low calcium. Anti-aFGF antibody inhibited cell growth significantly only at low calcium concentrations. From these observations, an aFGF autocrine system including the apparent translocation of aFGF receptors may explain, if not entirely, the mechanism by which calcium regulates parathyroid cell growth. RP SAKAGUCHI, K (reprint author), NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892, USA. NR 39 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1992 VL 267 IS 34 BP 24554 EP 24562 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA263 UT WOS:A1992KA26300062 PM 1280262 ER PT J AU STEVEN, AC GREENSTONE, HL BOOY, FP BLACK, LW ROSS, PD AF STEVEN, AC GREENSTONE, HL BOOY, FP BLACK, LW ROSS, PD TI CONFORMATIONAL-CHANGES OF A VIRAL CAPSID PROTEIN - THERMODYNAMIC RATIONALE FOR PROTEOLYTIC REGULATION OF BACTERIOPHAGE-T4 CAPSID EXPANSION, COOPERATIVITY, AND SUPER-STABILIZATION BY SOC BINDING SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CONFORMATIONAL CHANGE; VIRAL CAPSID PROTEIN; BACTERIOPHAGE-T4; DIFFERENTIAL SCANNING CALORIMETRY; CRYOELECTRON MICROSCOPY ID HEAD-MATURATION PATHWAY; MOLECULAR-ORGANIZATION; ELECTRON-MICROSCOPY; SURFACE LATTICE; TRANSFORMATION; POLYHEADS; MUTANTS; SHELL; CRYSTALLINE; MORPHOLOGY C1 UNIV MARYLAND, SCH MED, DEPT BIOL CHEM, BALTIMORE, MD 21201 USA. NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. RP STEVEN, AC (reprint author), NIAMSD, STRUCT BIOL LAB, BLDG 6, ROOM 114, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. FU NIAID NIH HHS [AI 11676] NR 47 TC 60 Z9 60 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 5 PY 1992 VL 228 IS 3 BP 870 EP 884 DI 10.1016/0022-2836(92)90871-G PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KD721 UT WOS:A1992KD72100015 PM 1469720 ER PT J AU MELNICK, RL HUFF, J AF MELNICK, RL HUFF, J TI CHEMICALS AND HUMAN CANCER - REPLY SO LANCET LA English DT Letter ID CARCINOGENICITY; 1,3-BUTADIENE; EXPOSURE RP MELNICK, RL (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 5 PY 1992 VL 340 IS 8832 BP 1409 EP 1409 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KB202 UT WOS:A1992KB20200030 ER PT J AU LIOTTA, LA AF LIOTTA, LA TI NIH EXPENDITURES - EXTRAMURAL VERSUS INTRAMURAL SO SCIENCE LA English DT Letter RP LIOTTA, LA (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 4 PY 1992 VL 258 IS 5088 BP 1561 EP 1561 DI 10.1126/science.1455237 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA896 UT WOS:A1992KA89600003 PM 1455237 ER PT J AU SCHNEIDER, J AF SCHNEIDER, J TI NEUROSCIENCE AT NIH SO SCIENCE LA English DT Letter RP SCHNEIDER, J (reprint author), NIH,OFF DIRECTOR,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 4 PY 1992 VL 258 IS 5088 BP 1561 EP 1561 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA896 UT WOS:A1992KA89600002 ER PT J AU MEZEY, E PALKOVITS, M AF MEZEY, E PALKOVITS, M TI LOCALIZATION OF TARGETS FOR ANTIULCER DRUGS IN CELLS OF THE IMMUNE-SYSTEM SO SCIENCE LA English DT Article ID ACETYLCHOLINE-RECEPTOR GENES; GASTRIC-ACID SECRETION; DUODENAL-ULCER; DOPAMINE AGONISTS; MOLECULAR-CLONING; PARIETAL-CELLS; RAT; CYSTEAMINE; PROPIONITRILE; EXPRESSION AB The gastric mucosa consists of the epithelium, which lines the lumen, the lamina propria, and the muscularis mucosae. The targets of drugs used to treat stomach and duodenal ulcers are thought to be the acid-secreting parietal cells of the epithelium. However, immune cells in the lamina propria are the only cells that showed detectable messenger RNAs for histamine, muscarinic, gastrin, and dopamine receptors by in situ hybridization histochemistry. None of the epithelial cells expressed any of these messenger RNAs. Thus, the targets of antiulcer drugs seem to be cells of the immune system in the gut and not parietal cells, as generally believed. This conclusion may revise the thinking about ulcer formation and may shed light on the etiology of such chronic small intestinal diseases as Crohn's disease. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. RP MEZEY, E (reprint author), SEMMELWEIS UNIV MED,SCH MED,NEUROMORPHOL LAB,H-1085 BUDAPEST 8,HUNGARY. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 48 TC 79 Z9 81 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 DEC 4 PY 1992 VL 258 IS 5088 BP 1662 EP 1665 DI 10.1126/science.1333642 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA896 UT WOS:A1992KA89600041 PM 1333642 ER PT J AU PIGNON, JP ARRIAGADA, R IHDE, DC JOHNSON, DH PERRY, MC SOUHAMI, RL BRODIN, O JOSS, RA KIES, MS LEBEAU, B ONOSHI, T OSTERLIND, K TATTERSALL, MHN WAGNER, H AF PIGNON, JP ARRIAGADA, R IHDE, DC JOHNSON, DH PERRY, MC SOUHAMI, RL BRODIN, O JOSS, RA KIES, MS LEBEAU, B ONOSHI, T OSTERLIND, K TATTERSALL, MHN WAGNER, H TI A METAANALYSIS OF THORACIC RADIOTHERAPY FOR SMALL-CELL LUNG-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TRIALS AB Background. In spite of 16 randomized trials conducted during the past 15 years, the effect of thoracic radiotherapy on the survival of patients with limited small-cell lung cancer remains controversial. The majority of these trials did not have enough statistical power to detect a difference in survival of 5 to 10 percent at five years. This meta-analysis was designed to evaluate the hypothesis that thoracic radiotherapy contributes to a moderate increase in overall survival in limited small-cell lung cancer. Methods. We collected individual data on all patients enrolled before December 1988 in randomized trials comparing chemotherapy alone with chemotherapy combined with thoracic radiotherapy. Trials that included only patients with extensive disease were excluded. Results. The meta-analysis included 13 trials and 2140 patients with limited disease. A total of 433 patients with extensive disease were excluded. Overall, 1862 of 2103 patients who could be evaluated died; the median follow-up period for the surviving patients was 43 months. The relative risk of death in the combined-therapy group as compared with the chemotherapy group was 0.86 (95 percent confidence interval, 0.78 to 0.94; P = 0.001), corresponding to a 14 percent reduction in the mortality rate. The benefit in terms of overall survival at three years (+/-SD) was 5.4+/-1.4 percent. Indirect comparison of early with late radiotherapy and of sequential with non-sequential radiotherapy did not reveal any optimal time for treatment. There was a trend toward a larger reduction in mortality among younger patients: the relative risk of death in the combined-therapy as compared with the chemotherapy group ranged from 0.72 for patients less than 55 years old (95 percent confidence interval, 0.56 to 0.93) to 1.07 (0.70 to 1.64) for patients over 70. Conclusions. Thoracic radiotherapy moderately improves survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy. Identification of the optimal combination of chemotherapy and radiotherapy will require further trials. C1 NCI,BETHESDA,MD 20892. VANDERBILT UNIV,MED CTR,SCH MED,NASHVILLE,TN 37232. UNIV COLL & MIDDLESEX SCH MED,LONDON,ENGLAND. UNIV UPPSALA,S-75105 UPPSALA,SWEDEN. KANTONSSPITAL,CH-6004 LUZERN,SWITZERLAND. NORTHWESTERN UNIV,FAC MED,CHICAGO,IL 60611. HOP ST ANTOINE,F-75571 PARIS 12,FRANCE. OKAYAMA UNIV,OKAYAMA 700,JAPAN. RIGS HOSP,COPENHAGEN,DENMARK. ROYAL PRINCE ALFRED HOSP,CAMPERDOWN,NSW 2050,AUSTRALIA. UNION UNIV,ALBANY,NY 12208. RP PIGNON, JP (reprint author), INST GUSTAVE ROUSSY,DEPT BIOSTAT,F-94805 VILLEJUIF,FRANCE. RI Johnson, David/A-7437-2009 NR 8 TC 761 Z9 791 U1 1 U2 13 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 DEC 3 PY 1992 VL 327 IS 23 BP 1618 EP 1624 DI 10.1056/NEJM199212033272302 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KA260 UT WOS:A1992KA26000002 PM 1331787 ER PT J AU DURCAN, MJ MORGAN, PF AF DURCAN, MJ MORGAN, PF TI OPIOID RECEPTOR MEDIATION OF THE HYPOTHERMIC RESPONSE TO CAFFEINE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE CAFFEINE; NALOXONE; BODY TEMPERATURE; (MOUSE) ID DEPOLARIZATION-INDUCED RELEASE; PHOSPHODIESTERASE INHIBITORS; RECTAL TEMPERATURE; ADENOSINE-ANALOGS; NERVOUS-SYSTEM; CYCLIC-AMP; BRAIN; RAT; FORSKOLIN; ROLIPRAM AB Caffeine and other methylxanthines induce a dose-dependent reduction in core body temperature in mice. These experiments investigated the effects of neurotransmitter and neuromodulator antagonists on caffeine-induced hypothermia. Pretreatment with the alpha2-adrenoceptor antagonist, atipamezole; the beta-adrenoceptor antagonist, propranolol; the dopamine antagonist, haloperidol; or the benzodiazepine receptor antagonist, flumazenil had no intrinsic effects on core body temperature nor did they interact significantly with the hypothermic effects of caffeine. The alpha1-adrenoceptor antagonist, prazosin and the 5-HT receptor antagonist, metergoline significantly enhanced the hypothermic effects of caffeine, probably involving a combined effect with their intrinsic hypothermic actions. Pretreatment with the opiate receptor antagonist, naloxone (3 mg/kg i.p.), had no intrinsic effect on core body temperature but attenuated the hypothermic effect of caffeine reflected in a parallel shift to the right in the caffeine dose-effect curve. The naloxone-induced attenuation of the hypothermic effects of caffeine was also seen to be dose-dependent. The results reveal that opiate receptors (but not adrenoceptors, 5-HT, dopamine or benzodiazepine receptors) may play a role in modulating the hypothermic action of caffeine and possibly other methylxanthines. C1 NIAAA,DICBR,NEURO GENET LAB,BETHESDA,MD 20892. BURROUGHS WELLCOME CO,DIV PHARMACOL,RES TRIANGLE PK,NC 27709. NR 45 TC 10 Z9 10 U1 0 U2 2 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 DEC 2 PY 1992 VL 224 IS 2-3 BP 151 EP 156 DI 10.1016/0014-2999(92)90799-A PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KB674 UT WOS:A1992KB67400007 PM 1334837 ER PT J AU WALKER, WG NEATON, JD CUTLER, JA NEUWIRTH, R COHEN, JD AF WALKER, WG NEATON, JD CUTLER, JA NEUWIRTH, R COHEN, JD TI RENAL-FUNCTION CHANGE IN HYPERTENSIVE MEMBERS OF THE MULTIPLE RISK FACTOR INTERVENTION TRIAL - RACIAL AND TREATMENT EFFECTS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BLOOD-PRESSURE; DISEASE; PROGRESSION; MRFIT; AGE; INSUFFICIENCY; DECLINE; MEN AB Objective.-To evaluate the contribution of mild to moderate hypertension to progressive loss of renal function by analysis of renal function data from the Multiple Risk Factor Intervention Trial. Design.-The cohort of men with mild to moderate hypertension (baseline diastolic blood pressure greater-than-or-equal-to 90 mm Hg), randomized to a special intervention (SI) group or usual care (UC) group, were examined for change in renal function based on individual reciprocal creatinine slopes over an average of 7 years' follow-up as the outcome measure. Contribution of blood pressure control during follow-up, age, race, and blood pressure at entry were assessed. Participants.-The cohort of 5524 (463 black, 5061 nonblack) hypertensive men receiving no therapy at entry provided the data for the present analysis. Results.-Blood pressure control was similar for black and white participants, but significant decline in reciprocal creatinine slope was found for black men (mean slope, -0.0090+/-0.0013 dL/mg/y) compared with white men (+0.0018+/-0.0004 dL/mg/y) (P<.001 for difference between blacks and whites). Decline in renal function was also greater among individuals with elevated systolic (P<.001) as well as diastolic blood pressure (P<.001), and older individuals (P<.001). No difference between the SI and UC groups was seen in reciprocal creatinine slopes, but in both groups combined, treatment that maintained diastolic blood pressure below an average value of 95 mm Hg was associated with stable or improving renal function, whereas participants whose blood pressure remained 95 mm Hg or greater continued to decline at -0.0013+/-0.0009 dL/mg/y (P=.007 for difference). Separate examination of the subset of black men (n=463) failed to show such a difference. Conclusions.-Effective blood pressure control was associated with stable or improving renal function in nonblacks but not in blacks. These findings emphasize the importance of blood pressure control to maintain adequate renal function in hypertensive white men and raise important questions about the relationship of pressure reduction and renal function change in blacks. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,MINNEAPOLIS,MN 55455. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. ST LOUIS UNIV,MED CTR,PREVENT CARDIOL PROGRAMS,ST LOUIS,MO 63103. NR 43 TC 249 Z9 252 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 2 PY 1992 VL 268 IS 21 BP 3085 EP 3091 DI 10.1001/jama.268.21.3085 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KA002 UT WOS:A1992KA00200031 PM 1433739 ER PT J AU STETLERSTEVENSON, M AF STETLERSTEVENSON, M TI THE T(14/18) TRANSLOCATION IN HODGKINS-DISEASE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; GENE REARRANGEMENT; ANTIGEN RECEPTOR; BETA-CHAIN; IMMUNOGLOBULIN RP STETLERSTEVENSON, M (reprint author), NCI,DIV CANC BIOL DIAGNOSIS & CTR,PATHOL LAB,BLDG 10,RM 2N-108,BETHESDA,MD 20892, USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 2 PY 1992 VL 84 IS 23 BP 1770 EP 1771 DI 10.1093/jnci/84.23.1770 PG 2 WC Oncology SC Oncology GA JZ628 UT WOS:A1992JZ62800001 PM 1433363 ER PT J AU JACOBS, IJ KOHLER, MF WISEMAN, RW MARKS, JR WHITAKER, R KERNS, BAJ HUMPHREY, P BERCHUCK, A PONDER, BAJ BAST, RC AF JACOBS, IJ KOHLER, MF WISEMAN, RW MARKS, JR WHITAKER, R KERNS, BAJ HUMPHREY, P BERCHUCK, A PONDER, BAJ BAST, RC TI CLONAL ORIGIN OF EPITHELIAL OVARIAN-CARCINOMA - ANALYSIS BY LOSS OF HETEROZYGOSITY, P53-MUTATION, AND X-CHROMOSOME INACTIVATION SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROPHYLACTIC OOPHORECTOMY; CANCER; GENE; P53 AB Background: It has been suggested that multiple sites of epithelial ovarian carcinoma on the peritoneal surface reflect polyclonal disease arising from multiple primary tumors in the peritoneal mesothelium, rather than monoclonal disease spread by metastases from one primary ovarian cancer. Purpose: The purpose of this study was to investigate whether ovarian cancer has a monoclonal or polyclonal origin. Methods: DNA specimens were obtained from peripheral blood lymphocytes (normal DNA) and from multiple tumor deposits of 17 women with epithelial ovarian carcinoma: primary tumors, metastatic deposits, and ascites. The clonal origin of each tumor was determined by performing (a) analysis to detect loss of heterozygosity at rive loci on chromosomes 5, 11, 13, and 17; (b) sequencing of exons 5-8 of the p53 gene; and (c) X-chromosome inactivation analysis of the phosphoglycerate kinase (PGK) gene. Results: In 15 of the 17 cases analyzed, there was clear evidence of monoclonal origin. The probability that the genetic events documented in these 15 cases occurred as independent events in each tumor deposit ranged from 2.5 x 10(-1) to 3.7 x 10(-16). In two cases, the pattern of allelic deletion and p53 gene mutation was compatible with either a monoclonal origin or origin from two primary ovarian tumors. Conclusions: The results did not support the hypothesis that ovarian cancer is a multifocal, polyclonal disease. Instead, the data suggest that sporadic epithelial ovarian carcinoma has either a monoclonal or a dual primary origin. Implications: These findings have important implications for understanding of the natural history of ovarian cancer and for clinical strategies aimed at prevention and early detection. Further studies will be required to determine the clonal origin of familial hereditary ovarian cancer. C1 DUKE COMPREHENS CANC CTR,DURHAM,NC. UNIV CAMBRIDGE,CANC RES CAMPAIGN,HUMAN CANC GENET GRP,CAMBRIDGE,ENGLAND. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GYNECOL ONCOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. RI Bast, Robert/E-6585-2011; Jacobs, Ian/F-1743-2013 OI Bast, Robert/0000-0003-4621-8462; Jacobs, Ian/0000-0002-8112-4624 NR 21 TC 146 Z9 148 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 2 PY 1992 VL 84 IS 23 BP 1793 EP 1798 DI 10.1093/jnci/84.23.1793 PG 6 WC Oncology SC Oncology GA JZ628 UT WOS:A1992JZ62800008 PM 1433368 ER PT J AU YEE, LK ALLEGRA, CJ STEINBERG, SM GREM, JL AF YEE, LK ALLEGRA, CJ STEINBERG, SM GREM, JL TI DECREASED CATABOLISM OF FLUOROURACIL IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS DURING COMBINATION THERAPY WITH FLUOROURACIL, LEUCOVORIN, AND INTERFERON ALPHA-2A SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; HUMAN-TISSUES; RAT-LIVER; PIG-LIVER; 5-FLUOROURACIL; PURIFICATION; DEGRADATION; INHIBITION; THYMIDINE; URACIL AB Background: We previously reported that recombinant interferon alpha-2a (IFN alpha-2a) therapy was associated with a dose-dependent decrease in fluorouracil (5-FU) clearance. Purpose: In this study, we used peripheral blood mononuclear cells (PBMCs), which are responsive to IFNs, as surrogate tissue to determine whether the change in clearance might be explained by decrease in 5-FU catabolism during IFN alpha-2a therapy. Methods: The study population consisted of 45 patients with adenocarcinoma arising in the gastrointestinal tract. Thirty-seven patients received therapy containing IFN alpha-2a at a median dose of 5 million U/m2 per day (range, 1.7-7.5 million U/m2 per day) starting on day 1 and continuing through either day 7 or day 14 in conjunction with intravenous high-dose leucovorin (LV) followed by bolus 5-FU on days 2-6. Eight patients received the same schedule of 5-FU and LV daily for 5 days without IFN alpha-2a but with granulocyte-macrophage colony-stimulating factor starting on day 6 and ending at least 3 days prior to the start of the next cycle. Peripheral blood was collected during 70 cycles on days 1, 2, and 4 prior to the daily treatment with IFN alpha-2a + 5-FU + LV and during 19 cycles on days 1 and 4 prior to the daily treatment with 5-FU + LV without IFN alpha-2a. In a given patient cycle, matched samples were drawn at approximately the same time of day. PBMCs were isolated, and the intact cells were exposed to 4 muM [H-3]5-FU, and the formation of [H-3]dihydrofluorouracil was determined by reverse-phase high-performance liquid chromatography. Results: In 47 matched patient cycles from IFN alpha-2a + 5-FU + LV-treated patients in which samples were available on days 1, 2, and 4, 5-FU catabolism decreased by 20% (P2 = .03) and 41% (P2 = .0001) from the baseline catabolic rate (2.5 +/- 0.2 pmol/min per 10(6) cells [mean +/- SE]) on days 2 and 4, respectively. Using information from all paired samples, the mean change from baseline on day 2 was -0.4 +/- 0.2 pmol/min per 106 cells (n = 54; P2 = .05), and the change from baseline on day 4 was -1.3 +/- 0.3 pmol/min per 10(6) cells (n = 63; P2 = .0001). In contrast, changes in 5-FU catabolism were not evident in the PBMCs of the reference population receiving 5-FU + LV without IFN alpha-2a. Conclusions: The magnitude of the change in 5-FU catabolism is similar to the magnitude of the decrease in 5-FU clearance in our previous study. These observations suggest that changes in 5-FU catabolism during therapy with IFN alpha-2a, 5-FU, and LV may account for the decreased 5-FU clearance. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,BLDG 8,RM 5101,BETHESDA,MD 20889. NR 23 TC 45 Z9 45 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 2 PY 1992 VL 84 IS 23 BP 1820 EP 1825 DI 10.1093/jnci/84.23.1820 PG 6 WC Oncology SC Oncology GA JZ628 UT WOS:A1992JZ62800013 PM 1433371 ER PT J AU MIYASAKA, H LI, SSL AF MIYASAKA, H LI, SSL TI MOLECULAR-CLONING, NUCLEOTIDE-SEQUENCE AND EXPRESSION OF A CDNA-ENCODING AN INTRACELLULAR PROTEIN TYROSINE PHOSPHATASE, PTPASE-2, FROM MOUSE TESTIS AND T-CELLS SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE MOUSE; PROTEIN TYROSINE PHOSPHATASE; CDNA CLONING; NUCLEOTIDE SEQUENCE; GENE EXPRESSION ID MALE GERM LINE; MULTIGENE FAMILY; KINASES; TRANSCRIPTION; HOMOLOGY; MEMBER; DOMAIN; GENE AB The PTP-2 cDNA encoding an intracellular protein tyrosine phosphatase (PTPase-2) was isolated and sequenced from mouse testis and T-cell cDNA libraries. This PTP-2 cDNA was found to be homologous to human PTP-TC and rat PTP-S, and contained 1,551 nucleotides, including 1,146 nucleotides encoding 382 amino acids as well as 5' (61 nucleotides) and 3' (344 nucleotides) non-coding regions. Northern blot analysis indicated that PTP-2 mRNA of 1.9 Kb was most abundant in testis and kidney, although it was also present in spleen, muscle, liver, heart and brain. C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. NR 36 TC 11 Z9 12 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 DEC 2 PY 1992 VL 118 IS 1 BP 91 EP 98 DI 10.1007/BF00249698 PG 8 WC Cell Biology SC Cell Biology GA KF558 UT WOS:A1992KF55800010 PM 1283199 ER PT J AU SONG, LJ NAGEL, JE CHREST, FJ COLLINS, GD ADLER, WH AF SONG, LJ NAGEL, JE CHREST, FJ COLLINS, GD ADLER, WH TI COMPARISON OF CD3 AND CD2 ACTIVATION PATHWAYS IN T-CELLS FROM YOUNG AND ELDERLY ADULTS SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE AGING; CD2; CD3; LYMPHOCYTE-T AB The ability of purified T cells to be activated by immobilized anti-CD3 and soluble anti-CD2 monoclonal antibodies (mAbs) was compared using cells from young and old donors. Purified T cells from elderly humans activated with immobilized anti-CD3 mAb incorporated less [H-3]thymidine (58,780 vs 92,258 cpm; p<0.02) into cellular DNA, and secreted less IL-2 into the culture supernatants than did T cells from young donors. In contrast, T cells activated with anti-CD2 mAbs displayed no age-related differences in proliferation or IL-2 production. Anti-CD2 stimulation resulted in equal IL-2 synthesis by cells from young and old donors that was comparable to the amount produced_by cells from elderly donors stimulated with immobilized anti-CD3. Northern blot analysis of early cell cycle gene expression by anti-CD2 activated T cells demonstrated no age differences in the expression of p55 IL-2R or c-myc specific mRNA, although T cells from elderly individuals activated with immobilized anti-CD3 showed statistically significant decreases in both mRNAs. T cell receptor beta chain mRNA levels did not differ between cells from young or old donors after activation by either anti-CD3 or anti-CD2. The discordance in proliferative ability, IL-2 secretion, and specific mRNA expression between T cells from elderly donors activated through the CD3-TCR complex or by soluble anti-CD2 mAbs provides additional evidence for a multifactorial causation of age-related T cell proliferative defects, and may indicate that the difference in proliferative ability is, in part, attributable to responsiveness to secreted IL-2. C1 NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 0 TC 9 Z9 9 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD DEC PY 1992 VL 4 IS 4 BP 307 EP 315 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA KA680 UT WOS:A1992KA68000006 PM 1363463 ER PT J AU KRIEG, AM GOURLEY, MF KLINMAN, DM PERL, A STEINBERG, AD AF KRIEG, AM GOURLEY, MF KLINMAN, DM PERL, A STEINBERG, AD TI HETEROGENEOUS EXPRESSION AND COORDINATE REGULATION OF ENDOGENOUS RETROVIRAL SEQUENCES IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID MAMMARY-TUMOR VIRUS; SYSTEMIC LUPUS-ERYTHEMATOSUS; HUMAN DNA; T-CELLS; SJOGRENS-SYNDROME; MESSENGER-RNAS; MICE; ANTIBODIES; PROTEINS; ELEMENTS AB This study examines the expression of human endogenous retroviral or retroviral-like (ERV) sequences in peripheral blood mononuclear cells (PBMC). Probes to 12 human ERV were used in Northern analyses of 38 patients with autoimmune muscle diseases and 31 blood donor controls. All patients and controls expressed multiple classes of ERV RNA. This expression was quite heterogenous: for each of the nine ERV classes for which expression was detected, some individuals showed high RNA levels whereas others showed low levels. ERV expression was independent of disease and autoantibody production. Statistical analysis of densitometric data indicated that expression of several classes of ERV was coordinately regulated. ERV expression in individual patients showed coordinate fluctuations with time. These studies demonstrate the heterogeneity and coordinate regulation of human ERV expression. To evaluate whether ERV expression might be affected by lymphocyte activation, PBMC were cultured with or without lymphocyte mitogens before RNA extraction. These studies demonstrated complex changes in ERV expression after lymphocyte activation. Murine ERV have several immunoregulatory activities. If human ERV have analogous effects, their heterogeneous expression and association with lymphocyte activation may have important biologic consequences. C1 NIAMSD,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,BETHESDA,MD 20892. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,DEPT MOLEC MED & IMMUNOL,BUFFALO,NY 14263. RP KRIEG, AM (reprint author), UNIV IOWA HOSP & CLIN,DEPT INTERNAL MED,IOWA CITY,IA 52242, USA. OI Perl, Andras/0000-0002-5017-1348 NR 54 TC 37 Z9 37 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 1992 VL 8 IS 12 BP 1991 EP 1998 DI 10.1089/aid.1992.8.1991 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA KF475 UT WOS:A1992KF47500007 PM 1493049 ER PT J AU CIRONE, M ZOMPETTA, C ANGELONI, A ABLASHI, DV SALAHUDDIN, SZ PAVAN, A TORRISI, MR FRATI, L FAGGIONI, A AF CIRONE, M ZOMPETTA, C ANGELONI, A ABLASHI, DV SALAHUDDIN, SZ PAVAN, A TORRISI, MR FRATI, L FAGGIONI, A TI INFECTION BY HUMAN HERPESVIRUS-6 (HHV-6) OF HUMAN LYMPHOID T-CELLS OCCURS THROUGH AN ENDOCYTIC PATHWAY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID EPSTEIN-BARR-VIRUS; HERPES-SIMPLEX VIRUS-1; GLYCOPROTEIN-D; LYMPHOCYTES-T; HIV-1; INTERNALIZATION; IDENTIFICATION; REPLICATION; ADSORPTION; BINDING AB We have analyzed by immunoelectron microscopy the early events of binding and internalization of human herpesvirus 6 (HHV-6, strain GS) on a susceptible T-lymphoblastoid cell line, HSB-2. The virions bound to the cell surface at 4-degrees-C were tightly associated with the plasma membrane. Gold immunolabeling of the viral envelope proteins was strong and specific. Warming at 37-degrees-C for different times showed viral internalization through smooth surfaced pits and vesicles. Fusion events of the virions with the cell plasma membrane were never observed. Gold immunolabeling performed in parallel experiments before or after viral internalization showed: (1) absence of viral envelope proteins on the cell plasma membranes at all times of internalization, again excluding fusion events; (2) entry of the virions with their envelopes. Treatment of the cells with chloroquine, a drug known to affect the endocytic pathway, led to an almost complete inhibition of viral infectivity, suggesting that the endocytosed virions are responsible for a successful infection. Comparable results were obtained using a second strain of HHV-6 (BA92), with biologic and molecular characteristics similar to the prototype strain Z29. The chloroquine inhibition was effective on two different T cell lines (HSB-2 and J-Jhan), as well as on phytohemagglutinin-stimulated peripheral blood mononuclear cells. C1 UNIV ROME LA SAPIENZA,DIPARTIMENTO MED SPERIMENTALE,I-00185 ROME,ITALY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. OI Angeloni, Antonio/0000-0003-4969-9548 NR 27 TC 11 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 1992 VL 8 IS 12 BP 2031 EP 2037 DI 10.1089/aid.1992.8.2031 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA KF475 UT WOS:A1992KF47500011 PM 1337259 ER PT J AU ALLEN, JP LITTEN, RZ AF ALLEN, JP LITTEN, RZ TI TECHNIQUES TO ENHANCE COMPLIANCE WITH DISULFIRAM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE DISULFIRAM; DISULFIRAM IMPLANTS; ENHANCED COMPLIANCE; PHARMACOTHERAPIES ID COMMUNITY-REINFORCEMENT APPROACH; KM ALDEHYDE DEHYDROGENASE; ALCOHOLISM-TREATMENT; METHADONE PATIENTS; IMPLANTATION; RAT; MAINTENANCE; THERAPY; TRIAL AB Pharmacodynamic benefits of disulfiram in the treatment ot alcoholism have yet to be clearly demonstrated. Nevertheless, research does suggest that disulfiram may well have positive effects on drinking if mediational compliance procedures are employed. This paper reviews research on four strategies for enhancing disulfiram compliance: implants, incentives, contracts, and patient information. Generalizations about the strategies are drawn and needs for future research are briefly addressed. RP ALLEN, JP (reprint author), NIAAA,DIV CLIN & PREVENT RES,TREATMENT RES BRANCH,ROOM 14C-20,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 38 TC 29 Z9 29 U1 3 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1992 VL 16 IS 6 BP 1035 EP 1041 DI 10.1111/j.1530-0277.1992.tb00695.x PG 7 WC Substance Abuse SC Substance Abuse GA KD409 UT WOS:A1992KD40900005 PM 1471757 ER PT J AU HARFORD, TC PARKER, DA GRANT, BF AF HARFORD, TC PARKER, DA GRANT, BF TI FAMILY HISTORY, ALCOHOL-USE AND DEPENDENCE SYMPTOMS AMONG YOUNG-ADULTS IN THE UNITED-STATES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOLISM; DEPENDENCE; FAMILY HISTORY ID ADOPTEES RAISED APART; PROBLEM DRINKING; HIGH-RISK; MEN; ABUSE; SONS; BEHAVIOR; PARENTS AB Drawing upon data from the National Longitudinal Survey of young adults, this paper examines the effects of family history of alcoholism and current alcohol use by the young adults. A multivariate analysis of the data from the study indicates that there are both main and interaction effects of family history and current alcohol use on dependence symptoms among the young adults. C1 CALIF STATE UNIV LONG BEACH,DEPT SOCIOL,LONG BEACH,CA 90840. RP HARFORD, TC (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,ROOM 14C26,PARKLAWN BLDG,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 32 TC 22 Z9 23 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1992 VL 16 IS 6 BP 1042 EP 1046 DI 10.1111/j.1530-0277.1992.tb00696.x PG 5 WC Substance Abuse SC Substance Abuse GA KD409 UT WOS:A1992KD40900006 PM 1471758 ER PT J AU GRANT, BF AF GRANT, BF TI DSM-III-R AND PROPOSED DSM-IV ALCOHOL-ABUSE AND DEPENDENCE, UNITED-STATES 1988 - A NOSOLOGICAL COMPARISON SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOL ABUSE; ALCOHOL DEPENDENCE; DSM-III-R; DSM-IV; NOSOLOGICAL COMPARISON AB The purpose of the present study was to compare DSM-III-R and the proposed DSM-IV (options 1 and 2) diagnostic criteria for alcohol abuse and dependence in a representative sample of the United States general population. Alcohol abuse and dependence diagnostic categories were contrasted in terms of prevalence and overlap. The prevalences of DSM-III-R and DSM-IV diagnoses of alcohol abuse and dependence combined were remarkably similar. However, disaggregation of abuse and dependence diagnoses showed that there were major discrepancies between the classification systems. Reasons for these discrepancies are discussed in terms of differences in the number of diagnostic criteria and the content of the DSM-III-R and DSM-IV abuse and dependence categories, the requirement for physiological dependence in DSM-IV classifications, the relationship between the abuse and dependence categories, and the impact of the duration criteria. RP GRANT, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,ROOM 14C-26,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 11 TC 30 Z9 30 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1992 VL 16 IS 6 BP 1068 EP 1077 DI 10.1111/j.1530-0277.1992.tb00701.x PG 10 WC Substance Abuse SC Substance Abuse GA KD409 UT WOS:A1992KD40900011 PM 1471761 ER PT J AU DAR, MS CLARK, M AF DAR, MS CLARK, M TI TOLERANCE TO ADENOSINES ACCENTUATION OF ETHANOL-INDUCED MOTOR INCOORDINATION IN ETHANOL-TOLERANT MICE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ETHANOL; N(6)-CYCLOHEXYLADENOSINE; MOTOR INCOORDINATION; CROSS-TOLERANCE; MICE ID RAT CEREBELLAR SYNAPTOSOMES; HETEROLOGOUS DESENSITIZATION; ADENYLATE-CYCLASE; RECEPTOR; METHYLXANTHINES; METABOLITES; CAFFEINE; RELEASE; SYSTEM AB Our previously published reports have provided data that have supported a functional correlation between ethanol-induced changes in the characteristics of adenosine receptor, adenosine uptake and release in the brain, and ethanol-induced motor incoordination. The present data demonstrated a cross-tolerance between ethanol and adenosine further supporting the hypothesis that brain adenosine modulates the motor impairing effects of ethanol. Mice that received (-)-N6-cyclohexyladenosine (CHA) [0.25 mg/kg/day, intraperitoneally (ip)] for 10 days exhibited marked attenuation (cross-tolerance) to acute ethanol-induced motor incoordination compared with chronic saline (ip) controls. The attenuation of acute ethanol-induced motor incoordination was essentially same in animals that received CHA (25 ng/5 mul/day for 10 days) by the intracerebroventricular (icv) route as opposed to the controls that chronically received artificial cerebral spinal fluid by the same route. Similarly, tolerance was exhibited to acute CHA (0.125 mg/kg ip and 12.5 ng/5 mul icv) by animals fed liquid ethanol (19.5 g/kg/24 hr) for 10 days compared with none in the pair-fed sucrose controls. Scatchard plots using cerebellar tissue homogenates from animals given chronic CHA or chronic ethanol indicated no change in B(max) and/or K(d) values for CHA binding when compared with CHA binding in tissues from their respective controls. However, a lack of any change in the binding characteristics cannot rule out the involvement of adenosine receptors in the observed cross-tolerance between ethanol and CHA. The results may suggest desensitization of adenosine A1 receptors due to chronic CHA and ethanol as an alternate possible explanation in the development of cross-tolerance between adenosine (CHA) and ethanol. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP DAR, MS (reprint author), E CAROLINA UNIV,SCH MED,DEPT PHARMACOL,GREENVILLE,NC 27858, USA. FU NIAAA NIH HHS [R01AA 07101] NR 31 TC 27 Z9 27 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1992 VL 16 IS 6 BP 1138 EP 1146 DI 10.1111/j.1530-0277.1992.tb00710.x PG 9 WC Substance Abuse SC Substance Abuse GA KD409 UT WOS:A1992KD40900020 PM 1471769 ER PT J AU SCANLON, MN LAZARWESLEY, E GRANT, KA KUNOS, G AF SCANLON, MN LAZARWESLEY, E GRANT, KA KUNOS, G TI PROOPIOMELANOCORTIN MESSENGER-RNA IS DECREASED IN THE MEDIOBASAL HYPOTHALAMUS OF RATS MADE DEPENDENT ON ETHANOL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ETHANOL; PROOPIOMELANOCORTIN; HYPOTHALAMUS; RAT ID BETA-ENDORPHIN; CYCLASE ACTIVITY; OPIOID-PEPTIDES; POMC GENE; BIOSYNTHESIS; INVOLVEMENT; CLONIDINE; EXPRESSION; METABOLISM; CULTURES AB It is thought that certain actions of ethanol involve an interaction with endogenous opioids, including proopiomelanocortin-derived peptides such as beta-endorphin. To examine this possibility, we used a sensitive and specific assay f or proopiomelanocortin mRNA to obtain an estimate of the activity of the endorphinergic system in the mediobasal hypothalamus and the pituitary of rats exposed for 10 days in an inhalation chamber to either ethanol or water. This protocol causes dependence in the ethanol-exposed group, as demonstrated by the presence of withdrawal seizures after cessation of treatment. While ethanol treatment did not affect proopiomelanocortin mRNA levels in the pituitary, the level in hypothalamus was significantly lower in the ethanol-treated animals than in controls. These results suggest that some effects of ethanol may involve the hypothalamic endorphinergic system. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PHYSIOL & PHARMACOL,WINSTON SALEM,NC 27103. NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,BETHESDA,MD. NR 27 TC 38 Z9 40 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1992 VL 16 IS 6 BP 1147 EP 1151 DI 10.1111/j.1530-0277.1992.tb00711.x PG 5 WC Substance Abuse SC Substance Abuse GA KD409 UT WOS:A1992KD40900021 PM 1471770 ER PT J AU MAUTNER, SL MAUTNER, GC HUNSBERGER, SA ROBERTS, WC AF MAUTNER, SL MAUTNER, GC HUNSBERGER, SA ROBERTS, WC TI COMPARISON OF COMPOSITION OF ATHEROSCLEROTIC PLAQUES IN SAPHENOUS VEINS USED AS AORTOCORONARY BYPASS CONDUITS WITH PLAQUES IN NATIVE CORONARY-ARTERIES IN THE SAME MEN SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GRAFTS; SURGERY AB This study describes quantitatively the components of athersclerotic plaques in saphenous vein grafts used for aortocoronary bypass and compares the findings with the plaques in the native coronary arteries in the same men. A total of 607 five-mm segments of saphenous veins and 797 five-mm segments of native coronary arteries were examined by computerized planimetric technique in 19 men, aged 39 to 82 years (mean 61), who had survived bypass operation for >1 year. Comparison of the mean percentages of the plaque components in saphenous vein grafts in place for 14 to 26 months with those of the native coronary arteries revealed significant differences: cellular fibrous tissue, 86 vs 7%; dense fibrous tissue, 13 vs 82%; p <0.05. As survival time after the bypass operation increased, composition of the plaques in the saphenous veins changed so that by approximately 80 months the amounts of cellular and dense fibrous tissue in both saphenous vein grafts and native coronary arteries were similar: 10 vs 16%, and 75 vs 71%; p = not significant. Thus, by about 7 years after a coronary bypass operation the composition of plaques in saphenous vein grafts is similar to that in the native coronary arteries of the same patients. C1 NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. RP MAUTNER, SL (reprint author), NHLBI,PATHOL RES BRANCH,BLDG 10,ROOM 2N258,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 37 Z9 37 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 DEC 1 PY 1992 VL 70 IS 18 BP 1380 EP 1387 DI 10.1016/0002-9149(92)90285-7 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KA272 UT WOS:A1992KA27200002 PM 1442604 ER PT J AU YANOVSKI, SZ LEET, M YANOVSKI, JA FLOOD, M GOLD, PW KISSILEFF, HR WALSH, BT AF YANOVSKI, SZ LEET, M YANOVSKI, JA FLOOD, M GOLD, PW KISSILEFF, HR WALSH, BT TI FOOD SELECTION AND INTAKE OF OBESE WOMEN WITH BINGE-EATING DISORDER SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE OBESITY; BINGE EATING; FOOD INTAKE; FOOD SELECTION; DEPRESSION ID BULIMIA; BEHAVIOR; EATERS; INDIVIDUALS; PATTERNS AB We studied food selection and intake of 19 women [body mass index (in kg/m2) < 30], 10 of whom met proposed DSM-IV criteria for binge-eating disorder (BED). All subjects ate two multicourse meals in the laboratory, and were given tape-recorded instructions at each meal either to binge or eat in a normal fashion. Subjects with BED consumed significantly more energy than did subjects without BED at both the binge [12 400 vs 8440 kJ (2963 vs 2017 kcal), P < 0.005] and normal [98 10 vs 6870 kJ (2343 vs 1640 kcal), P < 0.02] meals. During the binge meal subjects with BED consumed a greater percentage of energy as fat (38.9% vs 33.5%, P < 0.002) and a lesser percentage as protein (11.4% vs 15.4%, P < 0.01) than did subjects without BED. There were no differences in macronutrient composition of food choices between groups in the normal meal. Obese women who meet criteria for BED show differences in both intake and macronutrient composition of food choices from obese women who do not meet these criteria when asked to eat in a laboratory setting, supporting the validity of this new diagnosis. C1 ST LUKES ROOSEVELT HOSP,OBES RES CTR,NEW YORK,NY. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,DEPT VET SURG,NEW YORK,NY 10032. RP YANOVSKI, SZ (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BLDG 10,3S231,BETHESDA,MD 20892, USA. NR 23 TC 132 Z9 135 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1992 VL 56 IS 6 BP 975 EP 980 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JZ774 UT WOS:A1992JZ77400003 PM 1442665 ER PT J AU HO, GYF NELSON, K NOMURA, AMY POLK, BF BLATTNER, WA AF HO, GYF NELSON, K NOMURA, AMY POLK, BF BLATTNER, WA TI MARKERS OF HEATH STATUS IN AN HTLV-I-POSITIVE COHORT SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ACUPUNCTURE; LYMPHOCYTES; HTLV-I ID T-CELL-LEUKEMIA; VIRUS TYPE-I; BLOOD-DONORS; NATION-WIDE; ATLV HTLV; LYMPHOMA; CARRIERS; TRANSMISSION; JAPAN; RETROVIRUS AB The health effects of chronic human T-cell lymphotropic virus type I (HTLV-I) infection were examined in a cohort of Japanese men who had emigrated from Okinawa, Japan, and had been participants in a prospective study in Hawaii since 1965. In the present follow-up study carried out in 1987-1988, various health indicators were measured in the subjects, whose mean age was 72.5 years. Participation rates were lower in the HTLV-I seropositives than in the seronegatives (46.7% vs. 76.0%) in the greater-than-or-equal-to 75-year age group. Lack of participation was significantly correlated with a high HTLV-I antibody titer. Among the participants, seropositive subjects were significantly more likely than the seronegatives to have lymphocytopenia (32.7% vs. 17.7%) and mild anemia (25.5% vs. 14.1%) after adjustment for age and socioeconomic status. The seropositives also had a higher frequency of acupuncture therapy (age-adjusted odds ratios were 2.1 and 4.2 for 1-5 treatments and greater-than-or-equal-to 6 treatments. respectively). Proportions of subjects who had been hospitalized at least twice were higher among the seropositives in the oldest age groups, 70-74 years and greater-than-or-equal-to 75 years, but not in those aged 65-69 years. Although specific disease conditions were not identified in this study, hematologic data, treatment histories, and the correlation between participation status and HTLV-I antibody titers suggest that chronic HTLV-I infection may be associated with as yet undefined adverse health effects, particularly in older age groups. C1 KUAKINI MED CTR,HONOLULU,HI. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. FU NCI NIH HHS [N01 CP-EB-51023-21, R01-CA-33644] NR 46 TC 10 Z9 10 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1992 VL 136 IS 11 BP 1349 EP 1357 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KK950 UT WOS:A1992KK95000007 PM 1488961 ER PT J AU NIELSEN, DA DEAN, M GOLDMAN, D AF NIELSEN, DA DEAN, M GOLDMAN, D TI GENETIC-MAPPING OF THE HUMAN TRYPTOPHAN-HYDROXYLASE GENE ON CHROMOSOME-11, USING AN INTRONIC CONFORMATIONAL POLYMORPHISM SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BECKWITH-WIEDEMANN SYNDROME; HUMAN TYROSINE-HYDROXYLASE; AMINO-ACID HYDROXYLASES; SEROTONERGIC NEURONS; FUNCTIONAL DOMAINS; NERVOUS-SYSTEM; HUMAN GENOME; LOCUS; LOCALIZATION; EVOLUTION AB The identification of polymorphic alleles at loci coding for functional genes is crucial for genetic association and linkage studies. Since the tryptophan hydroxylase (TPH) gene codes for the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, it would be advantageous to identify a polymorphism in this gene. By examining introns of the human TPH gene by PCR amplification and analysis by the single-strand conformational polymorphism (SSCP) technique, an SSCP was revealed with two alleles that occur with frequencies of .40 and .60 in unrelated Caucasians. DNAs from 24 informative CEPH families were typed for the TPH intron polymorphism and analyzed with respect to 1 0 linked markers on chromosome 11, between p13 and p15, with the result that TPH was placed between D11S151 and D11S134. This region contains loci for several important genes, including those for Beckwith-Wiedemann syndrome and tyrosine hydroxylase. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP NIELSEN, DA (reprint author), NATL INST ALCOHOL ABUSE & ALCOHOLISM,NEUROGENET LAB,MOLEC GENET SECT,BLDG 10,ROOM 3C102,BETHESDA,MD 20892, USA. RI Nielsen, David/B-4655-2009; Dean, Michael/G-8172-2012; Goldman, David/F-9772-2010 OI Dean, Michael/0000-0003-2234-0631; Goldman, David/0000-0002-1724-5405 NR 37 TC 75 Z9 76 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1992 VL 51 IS 6 BP 1366 EP 1371 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA KC995 UT WOS:A1992KC99500019 PM 1463016 ER PT J AU STRIKER, GE AF STRIKER, GE TI KIDNEY-DISEASE AND HYPERTENSION IN BLACKS SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material RP STRIKER, GE (reprint author), NIDDKD,DIV KIDNEY UROL & HEMATOL DIS,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 1992 VL 20 IS 6 BP 673 EP 673 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA KD660 UT WOS:A1992KD66000025 PM 1463002 ER PT J AU SPARKS, SM AF SPARKS, SM TI EXPLORING ELECTRONIC SUPPORT GROUPS SO AMERICAN JOURNAL OF NURSING LA English DT Article RP SPARKS, SM (reprint author), NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,EDUC TECHNOL BRANCH,BETHESDA,MD 20209, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD DEC PY 1992 VL 92 IS 12 BP 62 EP & PG 0 WC Nursing SC Nursing GA KB438 UT WOS:A1992KB43800021 PM 1456319 ER PT J AU FELLEY, CP QIAN, JM MANTEY, S PRADHAN, T JENSEN, RT AF FELLEY, CP QIAN, JM MANTEY, S PRADHAN, T JENSEN, RT TI CHIEF CELLS POSSESS A RECEPTOR WITH HIGH-AFFINITY FOR PACAP AND VIP THAT STIMULATES PEPSINOGEN RELEASE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article ID VASOACTIVE INTESTINAL POLYPEPTIDE; CYCLASE-ACTIVATING POLYPEPTIDE; GUINEA-PIG STOMACH; ADENYLATE-CYCLASE; HYPOTHALAMIC POLYPEPTIDE; PANCREATIC ACINI; BINDING-SITES; RAT STOMACH; SECRETIN; PEPTIDE AB Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide of the secretin-vasoactive intestinal peptide (VIP) family. To investigate whether PACAP alters chief cell function, we prepared isolated chief cells (>90% pure) from guinea pig stomach. PACAP-38, PACAP-27, VIP, and secretin all caused a threefold increase in pepsinogen release. The dose-response curves of PACAP-38, PACAP-27, and VIP were biphasic, whereas with secretin it was not. The first phase comprised 40% of maximal release, and each of the three peptides (PACAP-38, PACAP-27, and VIP) were equipotent (EC50 0.1-0.3 nM). For the second phase, comprising 60% of maximal release, the relative potencies were PACAP-38 > PACAP-27 = VIP. I-125-labeled secretin, I-125-VIP, and I-125-PACAP-27 all demonstrated saturable binding to chief cells, Binding of both I-125-PACAP-27 and I-125-VIP was inhibited completely and with similar potencies by PACAP-38, PACAP-27, and VIP. Secretin had a >500-fold lower affinity than PACAP-38 for displacing both I-125-PACAP-27 and I-125-VIP. With I-125-secretin, secretin was the most potent, and was 197 times more potent than PACAP-38, which was 6-8 times more potent than both PACAP-27 and VIP. We conclude that both PACAP-38 and PACAP-27 stimulate pepsinogen secretion from dispersed chief cells. In contrast to a number of other tissues, no evidence for a high-affinity receptor that interacted only with PACAP was found. PACAP and VIP interact with equal high affinity with a common receptor and with low affinity with the secretin receptor. C1 NIDDKD,DIGEST DIS BRANCH,BLDG 10,RM 9C-103,BETHESDA,MD 20892. NR 36 TC 21 Z9 21 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 DEC PY 1992 VL 263 IS 6 BP G901 EP G907 PN 1 PG 7 WC Physiology SC Physiology GA KF375 UT WOS:A1992KF37500056 PM 1335692 ER PT J AU YEH, CK AMBUDKAR, IS KOUSVELARI, E AF YEH, CK AMBUDKAR, IS KOUSVELARI, E TI DIFFERENTIAL EXPRESSION OF EARLY RESPONSE GENES, C-JUN, C-FOS, AND JUN-B, IN A5 CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PROTOONCOGENES; SIGNAL TRANSDUCTION; PROTEIN KINASE-A; PROTEIN KINASE-C; CALCIUM ION; SALIVARY CELL LINE ID TRANSCRIPTIONAL ACTIVATION; STIMULATE TRANSCRIPTION; PROTEIN INTERACTS; BINDING; LINE; SEQUENCES; ELEMENT; CALCIUM; AP-1; C-JUN/AP-1 AB We examined the expression of c-fos, c-jun, and jun B after activation of different signal transduction pathways in the A5 rat salivary epithelial cell line. Stimulation of beta-adrenergic receptors by isoproterenol, or addition of 8-bromoadenosine 3',5'-cyclic monophosphate, induces the expression of c-fos and jun B by a protein kinase A-mediated pathway. Phorbol 12-myristate 13-acetate (PMA) induces the expression of all three genes, but with different kinetics. While c-fos and jun B mRNA levels increase early (1 h) after stimulation and transiently, those of c-jun remain higher than control even after stimulation for 8 h and return to basal levels by 24 h. Inhibitors of protein kinase C block the effect of PMA on c-fos, c-jun, and jun B expression, indicating that these genes are also regulated by a protein kinase C-mediated mechanism in A5 cells. Increases in cytosolic Ca2+ by A23187 or ionomycin induce only the expression of c-fos gene. This induction is abolished when A5 cells are loaded with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid before treatment with the ionophores, or when serum is excluded from the incubation medium. Exclusion of serum from the medium does not change the effects of isoproterenol or PMA on c-fos, c-jun, or jun B. These results strongly suggest that serum factors act synergistically with Ca2+ to induce c-fos expression in A5 cells. The studies presented here indicate that different signal transduction pathways operate in A5 cells for the induction of c-fos, c-jun, and jun B genes. RP YEH, CK (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1A-19,BETHESDA,MD 20892, USA. NR 35 TC 12 Z9 12 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 DEC PY 1992 VL 263 IS 6 BP G934 EP G938 PN 1 PG 5 WC Physiology SC Physiology GA KF375 UT WOS:A1992KF37500061 PM 1335693 ER PT J AU SCHULMAN, SP LAKATTA, EG FLEG, JL LAKATTA, L BECKER, LC GERSTENBLITH, G AF SCHULMAN, SP LAKATTA, EG FLEG, JL LAKATTA, L BECKER, LC GERSTENBLITH, G TI AGE-RELATED DECLINE IN LEFT-VENTRICULAR FILLING AT REST AND EXERCISE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AGING; DIASTOLIC FUNCTION; PEAK FILLING RATE ID HYPERTENSION; MYOCARDIUM; PRESSURE; CATECHOLAMINES; DETERMINANTS; RELAXATION; DISEASE; VOLUME; YOUNG; ADULT AB To determine whether the age-associated decline in resting left ventricular diastolic filling persists during aerobic exercise, rest and bicycle exercise filling indexes were measured from gated radionuclide blood pool scans in 88 healthy men aged 22-82 yr. To evaluate the effect of physical conditioning status on these age-related changes, a subset of the subjects consisted of endurance-trained senior athletes with a maximal O2 consumption of 50.5 +/- 5 compared with 32.6 +/- 7 ml . kg-1 . min-1 in age-matched controls. The contribution of beta-adrenergic stimulation to exercise-induced changes in filling was also evaluated by the administration of intravenous propranolol to another subset before testing. Peak filling rate increased progressively at all ages with increasing exercise work loads. The peak filling rates at rest, 50% maximal exercise, and maximum exercise inversely correlated with age (r = -0.64, -0.53, -0.64, respectively). Rest and exercise filling indexes in senior athletes were similar to those of sedentary older subjects. Propranolol decreased exercise peak filling rates in young (37.2 +/- 7.5 yr) but not in older (62.1 +/- 6 yr) subjects. Therefore, filling rates increase with exercise in both young and older healthy men, but age differences persist at comparable relative work loads. This decline is not secondary to a decline in physical conditioning status but appears to be related to a decrease in beta-adrenergic responsiveness in older individuals. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 34 TC 104 Z9 105 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD DEC PY 1992 VL 263 IS 6 BP H1932 EP H1938 PN 2 PG 7 WC Physiology SC Physiology GA KF377 UT WOS:A1992KF37700040 ER PT J AU POST, RM LEVERICH, GS ALTSHULER, L MIKALAUSKAS, K AF POST, RM LEVERICH, GS ALTSHULER, L MIKALAUSKAS, K TI LITHIUM-DISCONTINUATION-INDUCED REFRACTORINESS - PRELIMINARY-OBSERVATIONS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID BIPOLAR DISORDER AB The authors used a systematic life-chart methodology to observe four patients with bipolar disorder in whom long periods (6-15 years) of effective lithium prophylaxis were followed by relapses on lithium discontinuation. Once the drug was reinstituted, it was no longer effective. The incidence, predictors, and mechanisms underlying this phenomenon all require further systematic study. The current preliminary observations suggest an additional reason for caution when lithium discontinuation in the well-maintained patient is considered. RP POST, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 148 Z9 149 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 DEC PY 1992 VL 149 IS 12 BP 1727 EP 1729 PG 3 WC Psychiatry SC Psychiatry GA JZ879 UT WOS:A1992JZ87900015 PM 1443252 ER PT J AU MORRISON, JA BIRO, FM CAMPAIGNE, BN BARTON, BA SHUMANN, BC CRAWFORD, PB FALKNER, F SABRY, ZI KIMM, SYS LAKATOS, EE OBARZANEK, E PAYNE, GH HARLAN, WR SCHREIBER, GB AF MORRISON, JA BIRO, FM CAMPAIGNE, BN BARTON, BA SHUMANN, BC CRAWFORD, PB FALKNER, F SABRY, ZI KIMM, SYS LAKATOS, EE OBARZANEK, E PAYNE, GH HARLAN, WR SCHREIBER, GB TI OBESITY AND CARDIOVASCULAR-DISEASE - RISK-FACTORS IN BLACK-AND-WHITE GIRLS - THE NHLBI GROWTH AND HEALTH STUDY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; BOGALUSA HEART; YOUNG-ADULTS; BIRACIAL COMMUNITY; BODY-FAT; CHILDREN; PLASMA; DETERMINANTS; POPULATIONS; OVERWEIGHT AB Objectives. Obesity may be a possible explanation for the higher cardiovascular disease mortality in Black women compared with White women. The National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) is designed to assess factors associated with the development of obesity in Black and White preadolescent girls and its effects on major cardiovascular-disease risk factors. Methods. NGHS is a 5-year cohort study of 2379 girls, aged 9 through 10 years at entry. Anthropometry, blood pressure, and maturation staging are measured annually, and blood lipids biannually. Information on education, income, and family composition is also obtained from parents. Results. At baseline, compared with White girls, Black girls were slightly older, biologically more mature, taller, heavier, and had higher Quetelet Indices, skinfolds, and blood pressures. Black girls had lower triglycerides and higher HDL cholesterol than White girls. Total cholesterol and LDL cholesterol were similar in the two groups. Conclusions. Baseline descriptive characateristics of the NGHS cohort showed that, in subjects aged 9 and 10 years, racial differences in obesity and blood pressure were already present. C1 MARYLAND MED RES INST, 600 WYNDHURST AVE, BALTIMORE, MD 21210 USA. CHILDRENS HOSP MED CTR, CINCINNATI, OH 45229 USA. UNIV CALIF BERKELEY, BERKELEY, CA 94720 USA. NHLBI, BETHESDA, MD 20892 USA. UNIV MICHIGAN, ANN ARBOR, MI 48109 USA. WESTAT CORP, ROCKVILLE, MD USA. NR 38 TC 170 Z9 170 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1992 VL 82 IS 12 BP 1613 EP 1620 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KB440 UT WOS:A1992KB44000005 ER PT J AU BURKE, GL SAVAGE, PJ MANOLIO, TA SPRAFKA, JM WAGENKNECHT, LE SIDNEY, S PERKINS, LI LIU, K JACOBS, DR AF BURKE, GL SAVAGE, PJ MANOLIO, TA SPRAFKA, JM WAGENKNECHT, LE SIDNEY, S PERKINS, LI LIU, K JACOBS, DR TI CORRELATES OF OBESITY IN YOUNG BLACK-AND-WHITE WOMEN - THE CARDIA STUDY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CHILDREN; WEIGHT; ADULTS; RISK; MEN AB Objectives. Although differences in obesity between Blacks and Whites are well documented in adult women, less information is available on potential correlates of these differences, especially in young adults. Methods. The association between behavioral and demographic factors and body size was assessed in 2801 Black and White women aged 18 to 30 years. Results. Black women had significantly higher age-adjusted mean body mass index and subscapular skinfold thickness than did White women. Obesity had different associations with age and education across racial groups. A positive relationship between age and obesity was seen in Black women but not in White women, whereas a negative association between education and body size was noted only in White women. Potential contributing factors to the increased prevalence of obesity in Black women include a more sedentary lifestyle, higher energy intake, earlier menarche, and earlier age at first childbirth. Conclusions. The difference in obesity across race could not be explained completely by these factors, since within virtually all strata, Black women had higher body mass indexes. Further investigation is needed to develop interventional strategies to prevent or reduce excess levels of obesity in Black women. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. KAISER PERMANENTE MED CARE PROGRAM,DIV RES,OAKLAND,CA. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35294. RP BURKE, GL (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,300 S HAWTHORNE ST,WINSTON SALEM,NC 27103, USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48049, N01-HC-48048] NR 26 TC 108 Z9 112 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1992 VL 82 IS 12 BP 1621 EP 1625 DI 10.2105/AJPH.82.12.1621 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KB440 UT WOS:A1992KB44000006 PM 1456336 ER PT J AU GIFT, HC REISINE, ST LARACH, DC AF GIFT, HC REISINE, ST LARACH, DC TI THE SOCIAL IMPACT OF DENTAL PROBLEMS AND VISITS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Objectives. The purpose of this analysis was to assess selected social consequences of maintaining oral health and treating oral diseases. The associations among socioeconomic and demographic factors with time lost from work or school and reductions in normal activities are explored. Methods. Data were gathered as part of the 1989 National Health Interview Survey from 50 000 US households (117 000 individuals), representing 240 million persons. The oral health care supplement was analyzed using the software SUDAAN to produce standard errors for estimates based on complex multistage sample designs. Results. Because of dental visits or problems, 148 000 hours of work were lost per 100 000 workers, 117 000 hours of school were lost per 100 000 school-age children, and 17 000 activity days beyond work and school time were restricted per 100 000 individuals in 1989. Exploratory analyses suggest that sociodemographic groups have different patterns of such time loss and of reduced normal activities. Conclusions. Overall, there is low social impact individually from dental visits and oral conditions. At the societal level, however, such problems and treatments among disadvantaged groups appear to have a greater impact. C1 UNIV CONNECTICUT,SCH DENT MED,FARMINGTON,CT 06032. RP GIFT, HC (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,WESTWOOD BLDG,ROOM 536,BETHESDA,MD 20892, USA. NR 13 TC 157 Z9 161 U1 1 U2 7 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1992 VL 82 IS 12 BP 1663 EP 1668 DI 10.2105/AJPH.82.12.1663 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KB440 UT WOS:A1992KB44000013 PM 1456343 ER PT J AU BROWN, LM EVERETT, GD BURMEISTER, LF BLAIR, A AF BROWN, LM EVERETT, GD BURMEISTER, LF BLAIR, A TI HAIR DYE USE AND MULTIPLE-MYELOMA IN WHITE MEN SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID CANCER; COSMETOLOGISTS AB In recent reports, multiple myeloma has been linked to use of hair coloring products containing mutagenic and carcinogenic chemicals. A population-based case-control study in Iowa of 173 White men with multiple myeloma and 650 controls obtained information on hair dye use. Risk of multiple myeloma was significantly elevated (OR = 1.9) among hair dye users and was greatest among those using hair dyes at least once a month for a year or more (OR = 4.3). These data, along with results from other studies, suggest that use of hair dyes contributes to the development of multiple myeloma. C1 ORLANDO REG MED CTR INC,DEPT INTERNAL MED,ORLANDO,FL. UNIV IOWA,DEPT PREVENT MED,IOWA CITY,IA 52242. RP BROWN, LM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415C,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [ES 03099] NR 10 TC 29 Z9 29 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1992 VL 82 IS 12 BP 1673 EP 1674 DI 10.2105/AJPH.82.12.1673 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KB440 UT WOS:A1992KB44000016 PM 1456346 ER PT J AU CHOYKE, PL GLENN, GM WALTHER, MCM ZBAR, B WEISS, GH ALEXANDER, RB HAYES, WS LONG, JP THAKORE, KN LINEHAN, WM AF CHOYKE, PL GLENN, GM WALTHER, MCM ZBAR, B WEISS, GH ALEXANDER, RB HAYES, WS LONG, JP THAKORE, KN LINEHAN, WM TI THE NATURAL-HISTORY OF RENAL LESIONS IN VONHIPPEL-LINDAU DISEASE - A SERIAL CT STUDY IN 28 PATIENTS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CELL CARCINOMA; MANIFESTATIONS; CYSTS; NEOPLASMS; FEATURES; LOCUS AB OBJECTIVE. Von Hippel-Lindau disease is a multisystem disorder predisposing to renal cysts and cancer. The growth and development of these renal lesions have not been documented previously. We reviewed serial CT scans to determine the rates and patterns of growth of renal lesions associated with von Hippel-Lindau disease. SUBJECTS AND METHODS. Twenty-eight patients with von Hippel-Lindau disease and renal involvement, including the spectrum from simple cysts to solid masses, had follow-up examinations for at least 1 year (mean, 2.4 years; range, 1-12 years) with serial contrast-enhanced abdominal CT. Renal lesions were measured and characterized. Surgical correlation was available in 12 patients. RESULTS. Two hundred twenty-eight lesions (eight lesions per patient) were detected. On the basis of their CT appearance, 168 lesions (74%) were classified as cysts, 18 (8%) as cysts with solid components, and 42 (18%) as solid masses. Among 12 patients with pathologic confirmation, the solid components of cystic lesions and solid lesions almost always contained renal carcinoma. The majority of cysts remained the same size (71%) or enlarged (20%); 9% became smaller or entirely involuted during the follow-up period. Although it is generally presumed that renal cysts are precursors to cancers, the transformation of a simple cyst to a solid lesion was observed in only two patients. Among the 42 solid lesions, all but two enlarged with time, with a mean doubling time of 10 months. CONCLUSION. The renal lesions associated with von Hippel-Lindau disease exhibited wide differences in growth. The majority of renal cysts grew slowly but some involuted. Transition to solid renal cancer was rare among cysts. Complex cystic and solid lesions contained neoplastic tissue that uniformly enlarged. These data may be used to help predict the progression of renal lesions in von Hippel-Lindau disease. C1 GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. NCI,CANC DIAGNOSIS BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. NCI,IMMUNOBIOL LAB,FREDERICK,MD 21701. RP CHOYKE, PL (reprint author), NCI,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BLDG 10,ROOM 1C660,BETHESDA,MD 20892, USA. NR 30 TC 102 Z9 108 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 1992 VL 159 IS 6 BP 1229 EP 1234 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JZ240 UT WOS:A1992JZ24000017 PM 1442389 ER PT J AU SANDER, CA MEDEIROS, LJ WEISS, LM YANO, T SNELLER, MC JAFFE, ES AF SANDER, CA MEDEIROS, LJ WEISS, LM YANO, T SNELLER, MC JAFFE, ES TI LYMPHOPROLIFERATIVE LESIONS IN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY SYNDROME SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE COMMON VARIABLE IMMUNODEFICIENCY SYNDROME; LYMPH NODE; ATYPICAL LYMPHOID HYPERPLASIA; EPSTEIN-BARR VIRUS ID EPSTEIN-BARR VIRUS; CANCER; HYPOGAMMAGLOBULINEMIA; DEFICIENCY; DISORDERS; LYMPHOMA; TISSUES; CELLS AB We reviewed our experience with 30 nodal and extranodal lymphoid lesions from 17 patients with common variable immunodeficiency (CVID). Immunohistochemical studies were performed on biopsies from 15 patients, in situ hybridization for Epstein-Barr virus in nine cases, and gene rearrangement analysis on seven lesions. The biopsies were classified into four groups: malignant lymphoma (two cases); atypical lymphoid hyperplasia (eight cases); reactive lymphoid hyperplasia (14 cases); and chronic granulomatous inflammation (six cases). The two malignant lymphomas were diagnosed using histologic criteria; tissue was not available for the assessment of clonality. In one neoplasm, Epstein-Barr virus was identified in the tumor cells by in situ hybridization. The cases of reactive lymphoid hyperplasia and chronic granulomatous inflammation had no atypical architectural, cytologic, or immunohistochemical features. The cases of atypical lymphoid hyperplasia were of particular interest, as these patients had either widespread involvement or massive disease. The diagnosis of lymphoma was considered likely by the clinicians and, in three cases, the histologic slides were originally interpreted as malignant lymphoma by the referring pathologists. Although the architecture of these lesions appeared to be effaced on hematoxylin and eosin-stained sections, immunohistochemical analysis demonstrated preserved architecture with florid expansion of B-cell and T-cell compartments. In addition, clinical follow-up of these patients was benign. and gene rearrangement analysis in three lesions revealed no evidence of clonality. We conclude that the majority of lymphoid lesions in patients with CVID are benign. Immunohistochemical and gene rearrangement studies are particularly helpful in the assessment of cases of atypical lymphoid hyperplasia. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. CITY HOPE NATL MED CTR,DUARTE,CA 91010. RP SANDER, CA (reprint author), NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N109,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA 50341] NR 26 TC 84 Z9 86 U1 0 U2 1 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 DEC PY 1992 VL 16 IS 12 BP 1170 EP 1182 DI 10.1097/00000478-199212000-00004 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA KC319 UT WOS:A1992KC31900004 PM 1334378 ER PT J AU RAND, CS WISE, RA NIDES, M SIMMONS, MS BLEECKER, ER KUSEK, JW LI, VC TASHKIN, DP AF RAND, CS WISE, RA NIDES, M SIMMONS, MS BLEECKER, ER KUSEK, JW LI, VC TASHKIN, DP TI METERED-DOSE INHALER ADHERENCE IN A CLINICAL-TRIAL SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID MEDICATION; ASTHMA AB We studied patterns of inhaler usage in a sample of participants from two centers in the Lung Health Study clinical trial. The inhaler, containing either ipratropium bromide or a placebo, was prescribed to be taken as two inhalations three times daily. For 4 months we recorded adherence by both self-report (n = 95) and canister weight change (n = 70). We compared these results with data obtained from a microprocessor monitoring device, the Nebulizer Chronolog (NC), which records the date and time of each inhaler actuation. Seventy-three percent of the participants reported using the inhaler an average of three times daily; however, NC data showed that only 15% of the participants actually used the inhaler an average of 2.5 or more times per day. Canister weight overestimated adherence because only 62% of the NC sets contained the prescribed two actuations. Fourteen percent showed a pattern of actuation of their inhalers more than 100 times in a 3-h interval. We interpret this usage pattern to reflect deliberate emptying of inhalers to appear to be in good compliance with the prescribed program. We conclude that self-report and weighing of inhaler canisters overestimate adherence to the prescribed regimens. Furthermore, a substantial number of monitored inhaler users appear to deliberately dump their medication prior to follow-up visits. C1 JOHNS HOPKINS UNIV,SCH MED,DIV PULM & CRIT CARE MED,BALTIMORE,MD 21205. NIH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DIV PULM MED,LOS ANGELES,CA 90024. RP RAND, CS (reprint author), JOHNS HOPKINS ASTHMA & ALLERGY CTR,5501 HOPKINS BAYVIEW CIRCLE,BALTIMORE,MD 21224, USA. OI Wise, Robert/0000-0002-8353-2349 FU NHLBI NIH HHS [N01 HR-46016] NR 21 TC 229 Z9 233 U1 1 U2 9 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 DEC PY 1992 VL 146 IS 6 BP 1559 EP 1564 PG 6 WC Respiratory System SC Respiratory System GA KC195 UT WOS:A1992KC19500034 PM 1456575 ER PT J AU GESSAIN, A GOUT, O AF GESSAIN, A GOUT, O TI CHRONIC MYELOPATHY ASSOCIATED WITH HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) SO ANNALS OF INTERNAL MEDICINE LA English DT Review DE PARAPARESIS, TROPICAL SPASTIC; HTLV-I; NERVOUS SYSTEM DISEASES ID TROPICAL SPASTIC PARAPARESIS; CELL LEUKEMIA-VIRUS; CHRONIC PROGRESSIVE MYELOPATHY; POLYMERASE CHAIN-REACTION; BLOOD MONONUCLEAR-CELLS; NUCLEOTIDE-SEQUENCE ANALYSIS; ACTIVATED LYMPHOCYTES-T; CEREBROSPINAL-FLUID; PERIPHERAL-BLOOD; MULTIPLE-SCLEROSIS AB Purpose: To review the clinical, epidemiologic, immunologic, and virologic aspects of the chronic myelopathy associated with human T-cell leukemia/lymphoma virus type I (HTLV-I), currently called tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). Data Identification: Studies done after 1985, when TSP/HAM was first recognized, were identified by a computer search using MEDLARS II and CANCERLIT. Additional information was acquired from personal files and bibliographies of existing literature. Study Selection: A total of 400 articles, 90 book chapters, and 150 abstracts from meetings covering all aspects of HTLV-I and neurologic diseases were critically analyzed, and information from 250 publications was included. Results of Data Analysis: TSP/HAM is present in most HTLV-I endemic areas, with a prevalence ranging from 5.1 to 128 per 100 000 inhabitants. Up to 20% of patients develop TSP/HAM after transfusion of HTLV-I contaminated blood. Pathologic characteristics indicate a chronic meningomyelitis. The clinical features consist of a chronic progressive spastic paraparesis or paraplegia, sphincter disturbances, and minimal sensory loss. Supraspinal and peripheral nerve involvement is sometimes observed. High titers of HTLV-I-specific antibodies are present in the serum and cerebrospinal fluid. The high level of humoral and cellular immunologic response and the association of TSP/HAM with other immunologic diseases suggest an immune-mediated process. Corticosteroids and immunosuppressor treatment usually result in only short-term improvement. Conclusion: TSP/HAM is a common neurologic disease in many parts of the world. All patients with chronic progressive myelopathies should be tested for serum and cerebrospinal fluid HTLV-I-specific antibodies. Systematic screening of blood donors for HTLV-I is necessary to help prevent the dissemination of the virus and the occurrence of post-transfusional cases. C1 NINCDS,BETHESDA,MD 20892. RP GESSAIN, A (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A11,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 255 TC 147 Z9 149 U1 0 U2 2 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 DEC 1 PY 1992 VL 117 IS 11 BP 933 EP 946 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA JZ276 UT WOS:A1992JZ27600010 PM 1443956 ER PT J AU COLEMAN, EA FEUER, EJ AF COLEMAN, EA FEUER, EJ TI BREAST-CANCER SCREENING AMONG WOMEN FROM 65 TO 74 YEARS OF AGE IN 1987-88 AND 1991 SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE BREAST NEOPLASMS; MAMMOGRAPHY; BREAST SELF-EXAMINATION; MASS SCREENING; PHYSICAL EXAMINATION ID OLDER WOMEN; MAMMOGRAPHY; PHYSICIANS AB Objective: To compare breast cancer screening rates from the 1991 survey with data from 1987-88 for women aged 65 to 74. Design: Surveys of women from five communities. Settings: Five control communities of the National Cancer Institute's Breast Cancer Screening Consortium. Participants: White, non-Hispanic women, ages 65 to 74; 499 in 1987-88 and 2156 in 1991. Response rates for the first survey wave ranged by area from 65% to 77% and for the second survey wave, from 62% to 85%. Main Outcome Measure: Mammogram and clinical breast examination during the past year and performance of monthly breast self examination, with the screening rates in wave 2 directly standardized to the income and education distribution of wave 1 in each area. Results: Mammography use between waves increased significantly (P < 0.05 after adjusting for education, income, and age) in all but one area (from 19% to 33% in wave 1 to 35% to 59% in wave 2). Among women who had a mammogram, the percent who also had a clinical breast examination decreased between waves from 95% to 85% (P = 0.001). Conclusions: Mammography in older women increased dramatically over 3 years, although the use of clinical breast examination may be decreasing. C1 NIH,BETHESDA,MD 20892. RP COLEMAN, EA (reprint author), NCI,DCPC,APPL RES BRANCH,EPN 343,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CN-85122-01] NR 20 TC 70 Z9 70 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 1 PY 1992 VL 117 IS 11 BP 961 EP 966 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JZ276 UT WOS:A1992JZ27600012 PM 1443958 ER PT J AU MCFARLAND, HF FRANK, JA ALBERT, PS SMITH, ME MARTIN, R HARRIS, JO PATRONAS, N MALONI, H MCFARLIN, DE AF MCFARLAND, HF FRANK, JA ALBERT, PS SMITH, ME MARTIN, R HARRIS, JO PATRONAS, N MALONI, H MCFARLIN, DE TI USING GADOLINIUM-ENHANCED MAGNETIC-RESONANCE-IMAGING LESIONS TO MONITOR DISEASE-ACTIVITY IN MULTIPLE-SCLEROSIS SO ANNALS OF NEUROLOGY LA English DT Article ID RELAPSING PATIENTS; SERIAL; MRI; BRAIN; DIAGNOSIS; BREAKDOWN; DTPA; CT AB The highly variable clinical course and the lack of a direct measurement of disease activity have made evaluation of experimental therapies in multiple sclerosis (MS) difficult. Recent studies indicate that clinically silent lesions can be demonstrated by magnetic resonance imaging (MRI) in patients with mild relapsing-remitting MS. Thus, MRI may provide a means for monitoring therapeutic trials in the early phase of MS. We studied 12 patients longitudinally for 12 to 21 months with monthly gadolinium (Gd)-enhanced MRIs. The data have been used to identify the most effective design of a clinical trial using Gd-enhanced lesions as the outcome measure. Frequent (> 1/mo) Gd-enhancing lesions were observed in 9 of the 12 patients, indicating that the disease is active even during the early phase of the illness. The frequency of the lesions was not constant; there was marked fluctuation in lesion number from month to month. However, the magnitude of the peak number of lesions and the frequency of the peaks varied among patients. Because of this variability, the most effective use of Gd-enhancing lesions as an outcome measure in a dinical trial was a crossover design with study arms of sufficient duration to allow accurate estimation of lesion frequency. Monitoring Gd-enhancing lesions may be an effective tool to assist in the assessment of experimental therapies in early MS. C1 GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. NINCDS,BIOMETRY BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP MCFARLAND, HF (reprint author), NIH,BLDG 10,ROOM 5B16,BETHESDA,MD 20892, USA. NR 30 TC 291 Z9 292 U1 1 U2 4 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1992 VL 32 IS 6 BP 758 EP 766 DI 10.1002/ana.410320609 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA KC150 UT WOS:A1992KC15000007 PM 1471866 ER PT J AU ANDERSON, RV SIEGMAN, MG BALABAN, RS CECKLER, TL SWAIN, JA AF ANDERSON, RV SIEGMAN, MG BALABAN, RS CECKLER, TL SWAIN, JA TI HYPERGLYCEMIA INCREASES CEREBRAL INTRACELLULAR ACIDOSIS DURING CIRCULATORY ARREST SO ANNALS OF THORACIC SURGERY LA English DT Article ID CARDIOPULMONARY BYPASS; MAGNETIC-RESONANCE; ENERGY-METABOLISM; BRAIN; ISCHEMIA; HYPOXIA; SPECTROSCOPY; RECOVERY; LACTATE; GLUCOSE AB Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess cerebral high-energy phosphate metabolism and intracellular pH in normoglycemic and hyperglycemic sheep during hypothermic circulatory arrest. Two groups of sheep (n = 8 per group) were placed in a 4.7-T magnet and cooled to 15-degrees-C using cardiopulmonary bypass. Spectra were acquired before and during circulatory arrest and during reperfusion and rewarming. Intracellular pH and adenosine triphosphate levels decreased during circulatory arrest. Compared with the normoglycemic animals, the hyperglycemic group was significantly more acidotic with the greatest difference observed during the first 20 minutes of reperfusion (6.40 +/- 0.08 versus 6.08 +/- 0.06, p < 0.001). Intracellular pH returned to baseline after 30 minutes of reperfusion in the normoglycemic group but did not reach baseline until 1 hour of reperfusion in the hyperglycemic animals. Adenosine triphosphate levels were significantly higher in the hyperglycemic group during circulatory arrest. Repletion of adenosine triphosphate during reperfusion was similar for both groups. These results support the hypothesis that hyperglycemia during cerebral ischemia drives anaerobic glycolysis and thus leads to increased lactate production and a decrease in the intracellular acidosis normally associated with ischemia. C1 UNIV NEVADA,SCH MED,DEPT SURG,DIV CARDIOVASC SURG,2040 W CHARLESTON BLVD,SUITE 601,LAS VEGAS,NV 89102. NHLBI,SURG BRANCH,BETHESDA,MD 20892. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 15 TC 25 Z9 26 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 DEC PY 1992 VL 54 IS 6 BP 1126 EP 1130 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA KA693 UT WOS:A1992KA69300016 PM 1449297 ER PT J AU SIEGMAN, MG ANDERSON, RV BALABAN, RS CECKLER, TL CLARK, RE SWAIN, JA AF SIEGMAN, MG ANDERSON, RV BALABAN, RS CECKLER, TL CLARK, RE SWAIN, JA TI BARBITURATES IMPAIR CEREBRAL METABOLISM DURING HYPOTHERMIC CIRCULATORY ARREST SO ANNALS OF THORACIC SURGERY LA English DT Article ID CARDIOPULMONARY BYPASS; MAGNETIC-RESONANCE; RAT-BRAIN; PROTECTION; HEART AB Barbiturates have been used as a method of cerebral protection in patients undergoing open heart operations. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess barbiturate-induced alterations in the cerebral tissue energy state during cardiopulmonary bypass, hypothermic circulatory arrest, and subsequent reperfusion. Sheep were positioned in a 4.7-T magnet with a radiofrequency coil over the skull. Nuclear magnetic resonance spectra were obtained at 37-degrees-C, during cardiopulmonary bypass before and after drug administration at 37-degrees-C and 15-degrees-C, throughout a 1-hour period of hypothermic circulatory arrest, and during a 2-hour reperfusion period. A group of animals (n = 8) was administered a bolus of sodium thiopental (40 mg/kg) during bypass at 37-degrees-C followed by an infusion of 3.3 mg . kg-1 . min-1 until hypothermic arrest. A control group of animals (n.= 8) received no barbiturate. The phosphocreatine/adenosine triphosphate ratio, reflecting tissue energy state, was lower during cardiopulmonary bypass at 15-degrees-C in the treated animals compared with controls (1.06 +/- 0.08 versus 1.36 +/- 0.17; p < 0.001). Lower phosphocreatine/adenosine triphosphate ratios were observed throughout all periods of arrest and reperfusion in the barbiturate-treated animals compared with controls (p less-than-or-equal-to 0.01). Thiopental prevented the increase in cerebral energy state normally observed with hypothermia and resulted in a decrease in the energy state of the brain during hypothermic circulatory arrest and subsequent reperfusion. These results suggest that thiopental administration before a period of hypothermic circulatory arrest may prove detrimental to the preservation of the energy state of the brain. C1 UNIV NEVADA,SCH MED,DEPT SURG,DIV CARDIOVASC SURG,2040 W CHARLESTON BLVD,SUITE 601,LAS VEGAS,NV 89102. NHLBI,SURG BRANCH,BETHESDA,MD 20892. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. ALLEGHENY SINGER HOSP,CARDIOVASC & PULM RES CTR,PITTSBURGH,PA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 12 TC 19 Z9 20 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 DEC PY 1992 VL 54 IS 6 BP 1131 EP 1136 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA KA693 UT WOS:A1992KA69300017 PM 1449298 ER PT J AU CHAMULITRAT, W JORDAN, SJ MASON, RP AF CHAMULITRAT, W JORDAN, SJ MASON, RP TI FATTY-ACID RADICAL FORMATION IN RATS ADMINISTERED OXIDIZED FATTY-ACIDS - INVIVO SPIN TRAPPING INVESTIGATION SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID MICROSOMAL LIPID-PEROXIDATION; LINOLEIC-ACID; AUTOXIDATION PRODUCTS; SOYBEAN LIPOXYGENASE; VITAMIN-E; HYDROPEROXIDES; GLUTATHIONE; MALONDIALDEHYDE; INITIATION; MECHANISM RP CHAMULITRAT, W (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 28 Z9 28 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC PY 1992 VL 299 IS 2 BP 361 EP 367 DI 10.1016/0003-9861(92)90288-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JZ248 UT WOS:A1992JZ24800025 PM 1332621 ER PT J AU BREIER, A BUCHANAN, RW ELKASHEF, A MUNSON, RC KIRKPATRICK, B GELLAD, F AF BREIER, A BUCHANAN, RW ELKASHEF, A MUNSON, RC KIRKPATRICK, B GELLAD, F TI BRAIN MORPHOLOGY AND SCHIZOPHRENIA - A MAGNETIC-RESONANCE-IMAGING STUDY OF LIMBIC, PREFRONTAL CORTEX, AND CAUDATE STRUCTURES SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL ASYMMETRY; BASAL GANGLIA; PARAHIPPOCAMPAL GYRUS; GLUCOSE-METABOLISM; NEURON NUMBER; WHITE MATTER; ABNORMALITIES; DOPAMINE; SYSTEM AB We used magnetic resonance imaging to examine the morphologic characteristics of the amygdala/hippocampus, prefrontal cortex, and caudate nucleus in 29 healthy volunteers matched for age, gender, and head of household socioeconomic status and 44 patients with chronic schizophrenia. Total volumes of these structures were determined from 3-mm contiguous coronal sections. Schizophrenic patients, compared with healthy controls, had significantly smaller right and left amygdala/hippocampal complex volumes, smaller right and left prefrontal volumes, and larger left caudate volumes. A secondary analysis revealed reductions in the right and left amygdala and the left hippocampus. In addition, prefrontal white matter, but not gray matter, was reduced in the schizophrenic patients. Moreover, the right white matter volume in schizophrenic patients was significantly related to right amygdala/hippocampal volume (r=.39), data that provide preliminary support for a hypothesis of abnormal limbic-cortical connection in schizophrenia. We studied the implications of these data for the pathophysiology of schizophrenia. C1 UNIV MARYLAND, SCH MED, DEPT RADIOL, CATONSVILLE, MD 21228 USA. ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, WASHINGTON, DC 20032 USA. RP BREIER, A (reprint author), UNIV MARYLAND, SCH MED, MARYLAND PSYCHIAT RES CTR, DEPT PSYCHIAT, POB 21237, CATONSVILLE, MD 21228 USA. FU NIMH NIH HHS [MH40279, MH45074] NR 72 TC 414 Z9 420 U1 0 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 1992 VL 49 IS 12 BP 921 EP 926 PG 6 WC Psychiatry SC Psychiatry GA KB867 UT WOS:A1992KB86700001 PM 1449382 ER PT J AU BERMAN, KF TORREY, EF DANIEL, DG WEINBERGER, DR AF BERMAN, KF TORREY, EF DANIEL, DG WEINBERGER, DR TI REGIONAL CEREBRAL BLOOD-FLOW IN MONOZYGOTIC TWINS DISCORDANT AND CONCORDANT FOR SCHIZOPHRENIA SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; CEREBROVASCULAR CO2 REACTIVITY; PHYSIOLOGICAL DYSFUNCTION; HYPOFRONTALITY; ABNORMALITIES; ATTENTION; STROKE AB We addressed several questions regarding hypofunction of the prefrontal cortex ("hypofrontality") in schizophrenia by measuring regional cerebral blood flow during three different cognitive conditions in monozygotic twins who were discordant or concordant for schizophrenia or who were both normal. These questions included the prevalence of hypofrontality, the importance of genetic predisposition, and the role of long-term neuroleptic treatment. Significant differences between affected and unaffected discordant twins were found only during a task linked to the prefrontal cortex, the Wisconsin Card Sorting Test. During this condition, all of the twins with schizophrenia were hypofrontal compared with their unaffected co-twins, suggesting that, if appropriate cognitive conditions and control groups are used, hypofrontality can be demonstrated in the majority of, if not all, patients with schizophrenia. When unaffected co-twins of patients with schizophrenia were compared with twins who were both normal, no differences were observed, suggesting that nongenetic factors are important in the cause of the prefrontal physiologic deficit that appears to characterize schizophrenia. When concordant twins with a high- vs a low-dose lifetime history of neuroleptic treatment were compared, the twin receiving the higher dose was more hyperfrontal in six of eight pairs, suggesting that long-term neuroleptic treatment does not play a major role in hypofrontality. RP BERMAN, KF (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. FU NIMH NIH HHS [MH41176] NR 37 TC 164 Z9 165 U1 0 U2 6 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 DEC PY 1992 VL 49 IS 12 BP 927 EP 934 PG 8 WC Psychiatry SC Psychiatry GA KB867 UT WOS:A1992KB86700002 PM 1360197 ER PT J AU YANNUZZI, LA SORENSON, JA SOBEL, RS DALY, JR DEROSA, JT SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA GELLES, E GONET, R BURTON, TC CULVER, J METZGER, K KALBFLEISCH, N ZARLING, D FARBER, MD BLAIR, N STELMACK, T AXELROD, A WAITR, SE CROSS, A ROLNICK, C FLOM, T HALLER, J PUSIN, S CASSEL, G APPLEGATE, CA SEIGEL, D SPERDUTO, RD HILLER, R MOWERY, R CHEW, E TAMBOLI, A MILLER, DT SOWELL, AL GUNTER, EW DUNN, M SEDDON, JM SHAMBAN, K GELLES, E LENTO, D ALEXANDER, JA PHILLIPS, DA AF YANNUZZI, LA SORENSON, JA SOBEL, RS DALY, JR DEROSA, JT SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA GELLES, E GONET, R BURTON, TC CULVER, J METZGER, K KALBFLEISCH, N ZARLING, D FARBER, MD BLAIR, N STELMACK, T AXELROD, A WAITR, SE CROSS, A ROLNICK, C FLOM, T HALLER, J PUSIN, S CASSEL, G APPLEGATE, CA SEIGEL, D SPERDUTO, RD HILLER, R MOWERY, R CHEW, E TAMBOLI, A MILLER, DT SOWELL, AL GUNTER, EW DUNN, M SEDDON, JM SHAMBAN, K GELLES, E LENTO, D ALEXANDER, JA PHILLIPS, DA TI RISK-FACTORS FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID NUTRITION EXAMINATION SURVEY; 1ST NATIONAL-HEALTH; SPECTROMETRY; MACULOPATHY; HEART; ZINC AB Neovascular age-related macular degeneration (AMD) is one of five retinal disorders studied in the Eye Disease Case-Control Study. Data were obtained from 421 patients with neovascular AMD and 615 controls on a broad array of possible risk factors through interviews, clinical examinations, and laboratory analyses of blood samples. Decreased risk of neovascular AMD was associated with higher levels of carotenoids in the serum samples, higher horizontal cup-to-disc ratios, and use of postmenopausal exogenous estrogens in women. Increased risk of neovascular AMD was associated with cigarette smoking, higher levels of serum cholesterol, and parity greater than zero. No support was found for sunlight exposure, serum zinc levels, or iris color as risk factors for this disease. Although no association was found with a history of cardiovascular disease itself, the associations with post-menopausal exogenous estrogen use, cigarette smoking, and serum cholesterol level are consistent with a hypothesis linking risk factors for cardiovascular disease with neovascular AMD. The association noted between serum carotenoid levels and neovascular AMD supports the hypothesis that higher levels of micronutrients with antioxidant capabilities may decrease the risk of AMD. C1 NEI,BIOMETRY & EPIDEMIOL PROGRAM,BLDG 31,ROOM 6A24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV ILLINOIS,CHICAGO,IL 60680. JOHNS HOPKINS UNIV HOSP,WILMER EYE INST,BALTIMORE,MD 21205. CTR DIS CONTROL,CTR ENVIRONM HLTH & HYG CONTROL,DIV ENVIRONM HLTH LAB SCI,ATLANTA,GA 30333. ORKAND CORP,CTR COORDINATING,SILVER SPRING,MD. CTR PHOTOG READING,BOSTON,MA. CTR MACULAR GRADING READING,BALTIMORE,MD. NR 23 TC 396 Z9 404 U1 5 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 1992 VL 110 IS 12 BP 1701 EP 1708 PG 8 WC Ophthalmology SC Ophthalmology GA KC117 UT WOS:A1992KC11700022 ER PT J AU KRUESI, MJP FINE, S VALLADARES, L PHILIPS, RA RAPOPORT, JL AF KRUESI, MJP FINE, S VALLADARES, L PHILIPS, RA RAPOPORT, JL TI PARAPHILIAS - A DOUBLE-BLIND CROSSOVER COMPARISON OF CLOMIPRAMINE VERSUS DESIPRAMINE SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Article DE PARAPHILIA; OBSESSIVE-COMPULSIVE DISORDER; CLOMIPRAMINE; DESIPRAMINE; AFFECTIVE DISORDER ID OBSESSIVE-COMPULSIVE DISORDER; AGORAPHOBIA AB A relationship has been suggested between clinical presentation of paraphilias and obsessive-compulsive disorder (OCD) with respect to the unwanted repetitive nature and insight into the irrationality of the paraphiliac behavior. This has led to speculation that paraphiliac disorders might belong to an "obsessive compulsive spectrum." To address this issue, and because of the striking selective benefit of serotonin reuptake blocking antidepressants (such as clomipramine) in the treatment of OCD, 15 paraphiliacs entered a double-blind crossover comparison of clomipramine vs. desipramine preceded by a 2-week single-blind placebo period. Four subjects responded to placebo and were dropped from the study. Three others failed to complete the study. Although the study is limited by the small number of patients and the heterogeneity of the paraphilias, the observed benefit from both tricyclics (over the initial placebo) encourages further study. For the 8 subjects completing the protocol, there was no preferential response to the more specific serotonin reuptake inhibitor suggesting a difference in underlying pathophysiology between paraphilia and OCD. C1 FOGEL FDN & HUMAN SEXUAL INST,WASHINGTON,DC. UNIV BRITISH COLUMBIA,DIV CHILD PSYCHIAT,VANCOUVER V6T 1W5,BC,CANADA. RP KRUESI, MJP (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 50 Z9 50 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0004-0002 J9 ARCH SEX BEHAV JI Arch. Sex. Behav. PD DEC PY 1992 VL 21 IS 6 BP 587 EP 593 DI 10.1007/BF01542257 PG 7 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA KB226 UT WOS:A1992KB22600005 PM 1482282 ER PT J AU CAMPOS, H BLIJLEVENS, E MCNAMARA, JR ORDOVAS, JM POSNER, BM WILSON, PWF CASTELLI, WP SCHAEFER, EJ AF CAMPOS, H BLIJLEVENS, E MCNAMARA, JR ORDOVAS, JM POSNER, BM WILSON, PWF CASTELLI, WP SCHAEFER, EJ TI LDL PARTICLE-SIZE DISTRIBUTION - RESULTS FROM THE FRAMINGHAM OFFSPRING STUDY SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE LDL PARTICLE SIZE; CHOLESTEROL; PLASMA LIPOPROTEINS; TRIGLYCERIDES; GRADIENT GEL ELECTROPHORESIS; APOLIPOPROTEINS; DIETARY FAT INTAKE ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; SUBCLASS PATTERNS; HEART-DISEASE; RISK-FACTORS; FAMILIAL HYPERCHOLESTEROLEMIA; NONHUMAN-PRIMATES; APOLIPOPROTEIN-B; PLASMA; CHOLESTEROL AB Using 2-16% gradient gel electrophoresis, we examined low density lipoprotein (LDL) particle size in relation to plasma lipoproteins in 1,168 women and 1,172 men from the Framingham Offspring Study. In addition, we studied the effect of dietary intake on LDL size in a subset of the population. Seven LDL size peaks were identified, with the largest, LDL 1, being found in the density range 1.019-1.033 g/ml; LDL 2 and LDL 3 in d = 1.033-1.038 g/ml; LDL 4 and LDL 5 in d = 1.038-1.050 g/ml; and the smallest, LDL 6 and 7, in d = 1.050-1.063 g/ml. Seventy-seven percent of the population had one major and at least one minor LDL peak. Secondary LDL peaks accounted for 23% of the total LDL relative area, based on laser scanning densitometry. LDL size distribution was skewed toward larger LDL particles in women (prevalence of LDL 1, 30% and of LDL 2, 31%), whereas men exhibited a more symmetric distribution (prevalence or LDL 3, 42%). The prevalence of small (< 255 angstrom), dense (d > 1.038 g/ml) LDL particles 4-7 was 33% in men, 5% in premenopausal women, and 14% in postmenopausal women. In agreement with previous reports, small, dense LDL particles were significantly (p < 0.0001) associated with increased triglyceride and apolipoprotein (apo) B levels and decreased HDL cholesterol and apo A-1 levels. In addition, we found a significant (p < 0.0001) association between LDL cholesterol and LDL size. The highest LDL cholesterol levels were found among women with LDL 4 (148 mg/dl) and men with LDL 3-5 (138 mg/dl). In addition, the presence of LDL 3 or 4 as secondary peaks was significantly associated with higher LDL cholesterol levels, while smaller secondary LDL peaks were associated with higher triglyceride levels. We also found that compared with subjects with optimal LDL cholesterol levels (< 130 mg/dl), individuals with high-risk LDL cholesterol levels (greater-than-or-equal-to 160 mg/dl) had 1) a higher prevalence of LDL 3 and 4 (women only) and a lower prevalence of LDL 1 and 2 (women only) and 2) 11% higher LDL cholesterol to apo B ratios, even when matched for LDL particle size. Furthermore, low saturated fat and cholesterol intakes were significantly associated (p < 0.01) with smaller LDL particles. Therefore, the identification of small, dense LDL particles per se may not be a good indicator of coronary artery disease risk in population studies. Gender differences and environmental factors that affect triglyceride levels and LDL physical and chemical properties should be taken into consideration. In addition, LDL 3-5 particles in men and 4 in women are associated with the highest LDL cholesterol levels. C1 TUFTS UNIV,USDA HUMAN NUTR RES CTR,LIPID METAB LAB,711 WASHINGTON ST,BOSTON,MA 02111. BOSTON UNIV,SCH MED,BOSTON,MA 02215. BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA 02215. NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL-35243, HV83-03] NR 47 TC 196 Z9 199 U1 1 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD DEC PY 1992 VL 12 IS 12 BP 1410 EP 1419 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KB239 UT WOS:A1992KB23900006 PM 1450174 ER PT J AU COLBY, CL DUHAMEL, JR GOLDBERG, ME AF COLBY, CL DUHAMEL, JR GOLDBERG, ME TI POSTERIOR PARIETAL CORTEX AND RETINOCENTRIC SPACE SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article ID SACCADE-RELATED ACTIVITY; MACAQUE; NEURONS; MEMORY; 7A C1 CNRS,PHYSIOL NEUROSENSORIELLE LAB,F-75270 PARIS 06,FRANCE. RP COLBY, CL (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,ROOM 10C-101,BETHESDA,MD 20892, USA. RI Martin Arevalo, Elisa/L-4472-2014 OI Martin Arevalo, Elisa/0000-0002-4546-6440 NR 10 TC 1 Z9 1 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 1992 VL 15 IS 4 BP 727 EP 728 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA KC963 UT WOS:A1992KC96300031 ER PT J AU HALLETT, M AF HALLETT, M TI OPERATIONS OF THE MOTOR SYSTEM SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article ID CEREBELLUM; ELBOW RP HALLETT, M (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892, USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 1992 VL 15 IS 4 BP 754 EP 756 PG 3 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA KC963 UT WOS:A1992KC96300054 ER PT J AU ANANDATHEERTHAVARADA, HK BOYD, MR RAVINDRANATH, V AF ANANDATHEERTHAVARADA, HK BOYD, MR RAVINDRANATH, V TI CHARACTERIZATION OF A PHENOBARBITAL-INDUCIBLE CYTOCHROME-P-450, NADPH-CYTOCHROME P-450 REDUCTASE AND RECONSTITUTED CYTOCHROME-P-450 MONOOXYGENASE SYSTEM FROM RAT-BRAIN - EVIDENCE FOR CONSTITUTIVE PRESENCE IN RAT AND HUMAN BRAIN SO BIOCHEMICAL JOURNAL LA English DT Article ID AMINOPYRINE N-DEMETHYLASE; MOUSE-BRAIN; MICROSOMES; QUANTITATION; INDUCTION; PROTEINS; BINDING; ENZYME; FORMS AB Cytochrome P-450 was purified to apparent homogeneity from the brain microsomes of phenobarbital-treated rats. The specific content of the purified P-450 was 12.7 nmol/mg of protein. NADPH-cytochrome P-450 reductase (reductase) was also purified to apparent homogeneity from brain microsomes. The specific content was 34.7 mumol of cytochrome c reduced/min per mg of protein. The reduced carbon monoxide spectrum of purified P-450 exhibited a peak at 450 nm. Both the P-450 and the reductase moved as single bands on SDS/PAGE. The molecular masses of the purified P-450 and the reductase were determined to be 53.3 and 72.0 kDa respectively. The purified brain P-450 cross-reacted with antibodies to rat liver P-450IIB1/IIB2 when examined by Western immunoblotting, but no immunological similarity was observed with rat liver P-450IA1/IA2 or P-450IIE1. Purified rat brain reductase cross-reacted with antibodies to rat liver reductase. Further, immunoblot experiments with untreated rat and human brain microsomes using antisera to the purified rat brain P-450 and reductase indicated that these forms of P-450 and NADPH-cytochrome P-450 reductase exist constitutively in rat and human brain. Purified rat brain P-450 was reconstituted with purified NADPH-cytochrome P-450 reductase, deoxycholate and dilauroyl glyceryl 3-phosphocholine. NADPH-dependent N-demethylation of aminopyrine and morphine was observed in the reconstituted system. The catalytic-centre activities were 80.25 and 38.2 nmol of formaldehyde formed/min per nmol of P-450 respectively. The reconstituted system had a comparatively lower catalytic-centre activity for 7-ethoxycoumarin O-de-ethylase (10.5 nmol of product formed/min per nmol of P-450). C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,HOSUR RD,BANGALORE 560029,KARNATAKA,INDIA. NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NR 34 TC 24 Z9 24 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 DEC 1 PY 1992 VL 288 BP 483 EP 488 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB766 UT WOS:A1992KB76600022 PM 1463452 ER PT J AU GAHL, WA CHARNAS, L MARKELLO, TC BERNARDINI, I ISHAK, KG DALAKAS, MC AF GAHL, WA CHARNAS, L MARKELLO, TC BERNARDINI, I ISHAK, KG DALAKAS, MC TI PARENCHYMAL ORGAN CYSTINE DEPLETION WITH LONG-TERM CYSTEAMINE THERAPY SO BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY LA English DT Article ID NEPHROPATHIC CYSTINOSIS; CHILDREN; ACID; PHOSPHOCYSTEAMINE; COMPLICATIONS; INSUFFICIENCY; TRANSPORT; LYSOSOMES; FRACTIONS; PATIENT C1 NINCDS,BETHESDA,MD 20892. USAF,DEPT HEPAT PATHOL,WASHINGTON,DC 20306. RP GAHL, WA (reprint author), NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BETHESDA,MD 20892, USA. NR 35 TC 47 Z9 48 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 0885-4505 J9 BIOCHEM MED METAB B PD DEC PY 1992 VL 48 IS 3 BP 275 EP 285 DI 10.1016/0885-4505(92)90074-9 PG 11 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA KE920 UT WOS:A1992KE92000012 PM 1476793 ER PT J AU RIVAS, G INGHAM, KC MINTON, AP AF RIVAS, G INGHAM, KC MINTON, AP TI CALCIUM-LINKED SELF-ASSOCIATION OF HUMAN-COMPLEMENT C1(S-) SO BIOCHEMISTRY LA English DT Article ID ANALYTICAL ULTRACENTRIFUGATION; SEDIMENTATION EQUILIBRIUM; ANALYTICAL CENTRIFUGATION; BINDING-PROPERTIES; DOMAIN-STRUCTURE; CA-2+ BINDING; 1ST COMPONENT; C1S; CLR; MACROMOLECULES AB The weight-average molecular weight of C1sBAR, an activated serine protease subcomponent of human complement C1, has been measured by means of sedimentation equilibrium over a wide range of both protein and calcium ion concentrations. The combined data may be accounted for quantitatively by a simple model for Ca2+-dependent self-association of C1sBAR to a dimer. According to this model, the monomer contains a single Ca2+ binding site with K congruent-to 3 X 10(5) M-1, and the dimer contains three independent Ca binding sites, two having a Ca2+ affinity lower than that of the monomer (K congruent-to 3 X 10(4) M-1). The third binding site in the dimer, which presumably lies at the interface between the two amino-terminal alpha domains, has a higher Ca2+ affinity (K congruent-to 1 X 10(8) M-1) and provides the driving force for C1sBAR dimerization in the presence of calcium. C1 NIDDK, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. AMER RED CROSS, DEPT BIOCHEM, HOLLAND LAB, ROCKVILLE, MD 20855 USA. OI Rivas, German/0000-0003-3450-7478 FU NHLBI NIH HHS [HL21791] NR 41 TC 25 Z9 25 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 1 PY 1992 VL 31 IS 47 BP 11707 EP 11712 DI 10.1021/bi00162a006 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA483 UT WOS:A1992KA48300006 PM 1445906 ER PT J AU MCDONALD, LJ WAINSCHEL, LA OPPENHEIMER, NJ MOSS, J AF MCDONALD, LJ WAINSCHEL, LA OPPENHEIMER, NJ MOSS, J TI AMINO ACID-SPECIFIC ADP-RIBOSYLATION - STRUCTURAL CHARACTERIZATION AND CHEMICAL DIFFERENTIATION OF ADP-RIBOSE CYSTEINE ADDUCTS FORMED NONENZYMATICALLY AND IN A PERTUSSIS TOXIN-CATALYZED REACTION SO BIOCHEMISTRY LA English DT Article ID RIBOSYLTRANSFERASE ACTIVITY; TURKEY ERYTHROCYTES; CONFORMATIONAL-ANALYSIS; SKELETAL-MUSCLE; ALPHA-SUBUNIT; SUGAR RING; GI PROTEIN; NAD; ARGININE; NUCLEOTIDES AB ADP-ribosylation is a posttranslational modification of proteins by amino acid-specific ADP-ribosyltransferases. Both pertussis toxin and eukaryotic enzymes ADP-ribosylate cysteine residues in proteins and also, it has been suggested, free cysteine. Analysis of the reaction mechanisms of cysteine-specific ADP-ribosyltransferases revealed that free ADP-ribose combined nonenzymatically with cysteine. L- and D-cysteine, L-cysteine methyl ester, and cysteamine reacted with ADP-ribose, but alanine, serine, lysine, arginine, N-acetyl-L-cysteine, 2-mercaptoethanol, dithiothreitol, and glutathione did not. The H-1 NMR spectrum of the product, along with the requirement for both free sulfhydryl and amino groups of cysteine, suggested that the reaction produced a thiazolidine linkage. ADP-ribosylthiazolidine was labile to hydroxylamine and mercuric ion, unlike the ADP-ribosylcysteine formed by pertussis toxin and NAD in guanine nucleotide-binding (G-) proteins, which is labile to mercuric ion but stable in hydroxylamine. In the absence of G-proteins but in the presence of NAD and cysteine, pertussis toxin generated a hydroxylamine-sensitive product, suggesting that a free ADP-ribose intermediate, expected to be formed by the NADase activity of the toxin, reacted with cysteine. Chemical analysis, or the use of alternative thiol acceptors lacking a free amine, is necessary to distinguish the enzymatic formation of ADP-ribosylcysteine from nonenzymatic formation of ADP-ribosylthiazolidine, thereby differentiating putative NAD:cysteine ADP-ribosyltransferases from NAD glycohydrolases. C1 UNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM,SAN FRANCISCO,CA 94143. RP MCDONALD, LJ (reprint author), NHLBI,CELLULAR METABOL LAB,BLDG 10-5N-307,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR-01668, RR-4789]; NIGMS NIH HHS [GM22982] NR 43 TC 47 Z9 47 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 1 PY 1992 VL 31 IS 47 BP 11881 EP 11887 DI 10.1021/bi00162a029 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA483 UT WOS:A1992KA48300029 PM 1445918 ER PT J AU HUANG, PL CHEN, HC KUNG, HF HUANG, PL HUANG, P HUANG, HI LEEHUANG, S AF HUANG, PL CHEN, HC KUNG, HF HUANG, PL HUANG, P HUANG, HI LEEHUANG, S TI ANTI-HIV PLANT-PROTEINS CATALYZE TOPOLOGICAL CHANGES OF DNA INTO INACTIVE FORMS SO BIOFACTORS LA English DT Article DE AIDS; PLANT PROTEIN; DNA TOPOISOMERASE ID TOPOISOMERASE-II AB GAP 31, DAP 32 and DAP 30 comprise a new class of plant proteins with potent anti-HIV activity and insignificant cytotoxicity. We report here the identification and characterization of a new DNA enzyme activity in these three proteins. They irreversibly relax and decatenate supercoiled DNA, as well as catalyze double-stranded breakage to form linear DNA. The relaxed molecules are topologically inactive and no longer serve as substrates for DNA gyrase to form supercoils, phenomena similar to those of cellular topoisomerases in the presence of topoisomerase poisons. The ability of these anti-HIV agents to interrupt essential topological interconversions of DNA may provide a novel mechanism for their antiviral and antitumor actions. The presence of this new DNA topological enzyme activity in these plant proteins also suggests that their anti-HIV activity may not be merely a consequence of ribosome inactivation previously recognized. C1 NYU,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10016. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21701. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIAID NIH HHS [R01-AI31343] NR 10 TC 31 Z9 36 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0951-6433 J9 BIOFACTORS JI Biofactors PD DEC PY 1992 VL 4 IS 1 BP 37 EP 41 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA KE311 UT WOS:A1992KE31100006 PM 1337969 ER PT J AU PROSCHAN, MA FOLLMANN, DA WACLAWIW, MA AF PROSCHAN, MA FOLLMANN, DA WACLAWIW, MA TI EFFECTS OF ASSUMPTION VIOLATIONS ON TYPE-I ERROR RATE IN GROUP SEQUENTIAL MONITORING SO BIOMETRICS LA English DT Article DE CLINICAL TRIALS; GROUP SEQUENTIAL PROCEDURES; SEQUENTIAL MONITORING; TYPE-I ERROR ID CLINICAL-TRIALS; TESTS; CALENDAR AB We compare the degree to which the Type I error probability can be inflated by assumption violations under the different sequential monitoring schemes. For methods that assume equally spaced time intervals between ''looks'' at the data, we examine the effects of unequal spacings. For methods that do not specify the look times in advance, we examine the degree of Type 1 error inflation that can result when future look times are chosen based on data trends. We also evaluate a Bayesian method of monitoring from this non-Bayesian perspective of Type I error inflation. RP NHLBI, BIOSTAT RES BRANCH, FED BLDG, ROOM 2A11, 7550 WISCONSIN AVE, BETHESDA, MD 20892 USA. NR 17 TC 29 Z9 29 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD DEC PY 1992 VL 48 IS 4 BP 1131 EP 1143 DI 10.2307/2532704 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA KH704 UT WOS:A1992KH70400012 ER PT J AU WILLIAMS, PL PORTIER, CJ AF WILLIAMS, PL PORTIER, CJ TI EXPLICIT SOLUTIONS FOR CONSTRAINED MAXIMUM-LIKELIHOOD ESTIMATORS IN SURVIVAL SACRIFICE EXPERIMENTS SO BIOMETRIKA LA English DT Article DE ANIMAL CARCINOGENICITY EXPERIMENT; MAXIMUM LIKELIHOOD; MULTISTATE MODEL; NONPARAMETRIC ESTIMATION; SURVIVAL SACRIFICE DATA; TUMOR INCIDENCE RATE ID TESTS; CARCINOGENICITY AB Regulatory agencies routinely base conclusions regarding carcinogenicity of compounds tested in long-term animal studies on tests which are known to be biased under conditions of treatment lethality and tumour lethality. The recognition of these biases has led to a variety of proposed approaches which rely on survival and sacrifice data. Williams & Portier (1992) derived analytic expressions for maximum likelihood estimators of the tumour incidence rate and discrete death rates based on a discrete multistate model. A disadvantage of the proposed estimators was that they sometimes resulted in negative estimates of the tumour incidence rate. In this paper, explicit solutions for constrained estimators are derived under the imposition of boundary conditions for a study design with one or two interim sacrifices and a terminal sacrifice. For study designs with more than two interim sacrifices, alternative estimators of the tumour incidence rate and discrete death rates are developed heuristically by pooling data together from adjacent intervals. The ability of these estimators to predict the true tumour incidence rate under a variety of study conditions is evaluated by Monte Carlo simulation studies. C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. RP WILLIAMS, PL (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02215, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 15 TC 4 Z9 4 U1 0 U2 1 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 1992 VL 79 IS 4 BP 717 EP 729 DI 10.1093/biomet/79.4.717 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA KJ239 UT WOS:A1992KJ23900006 ER PT J AU HILLERY, PS COHEN, LA AF HILLERY, PS COHEN, LA TI STEREOPOPULATION CONTROL .10. RATE AND EQUILIBRIUM ENHANCEMENT IN THE FORMATION OF PHTHALIDES - THE CASE OF THE MISSING GROUND-STATE SO BIOORGANIC CHEMISTRY LA English DT Article ID ACIDS; LACTONIZATION; HYDROLYSIS C1 NIDDKD,BIOORGAN CHEM LAB,BLDG 8A,ROOM B1A09,BETHESDA,MD 20892. NR 28 TC 6 Z9 6 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 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD DEC PY 1992 VL 20 IS 4 BP 313 EP 322 DI 10.1016/0045-2068(92)90041-Z PG 10 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA KG247 UT WOS:A1992KG24700004 ER PT J AU SNIDER, RM PEREIRA, DA LONGO, KP DAVIDSON, RE VINICK, FJ LAITINEN, K GENCSEHITOGLU, E CRAWLEY, JN AF SNIDER, RM PEREIRA, DA LONGO, KP DAVIDSON, RE VINICK, FJ LAITINEN, K GENCSEHITOGLU, E CRAWLEY, JN TI UK-73,093 - A NONPEPTIDE NEUROTENSIN RECEPTOR ANTAGONIST SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID VENTRAL TEGMENTAL AREA; DOPAMINERGIC-NEURONS; SUBSTANTIA NIGRA; BINDING-SITES; RAT; CHOLECYSTOKININ; POTENT; MESENCEPHALON AB UK-73,093 was identified in a screening program as a compound able to displace [H-3]-neurotensin from its bovine brain receptor. We describe the discovery of this compound, species differences in receptor affinity and its characterization as a functional neurotensin antagonist in vitro and in vivo. C1 NIMH, BETHESDA, MD 20892 USA. RP PFIZER INC, DIV CENT RES, GROTON, CT 06340 USA. NR 25 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC PY 1992 VL 2 IS 12 BP 1535 EP 1540 DI 10.1016/S0960-894X(00)80423-0 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA KD889 UT WOS:A1992KD88900014 ER PT J AU HABER, MT NASHED, NT JERINA, DM AF HABER, MT NASHED, NT JERINA, DM TI ENANTIOMERIC COMPOSITION OF TRANS-DIHYDRODIOLS FORMED FROM MESO-K-REGION ARENE OXIDES BY MICROSOMAL EPOXIDE HYDROLASE SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE MESO-K-REGION ARENE OXIDES; BENZO[E]PYRENE; PYRENE; PHENANTHRENE; EPOXIDE HYDROLASE ID RAT-LIVER MICROSOMES; ABSOLUTE-CONFIGURATION; STEREOSELECTIVE METABOLISM; POLYCYCLIC-HYDROCARBONS; ENANTIOSELECTIVITY; DERIVATIVES; HYDROLYSIS; BENZOPYRENE; PHENANTHRENE; CONFORMATION AB Absolute configurations for the enantiomers of trans-4,5-dihydroxy-4,5-dihydrobenzo[e]pyrene were determined by the exciton chirality method and by correlation of physical properties of their (-)-(menthyloxy)acetyl diesters. Microsomal epoxide hydrolase catalyzed the hydrolysis of K-region arene oxides of benzo[e]pyrene, pyrene. and phenanthrene to trans-dihydrodiols containing 83 %, 86 %, and 42 % of the R,R enantiomer, respectively. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 32 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 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC PY 1992 VL 2 IS 12 BP 1729 EP 1734 DI 10.1016/S0960-894X(00)80465-5 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA KD889 UT WOS:A1992KD88900056 ER PT J AU BURKE, TR FORD, H OSHEROV, N LEVITZKI, A STEFANOVA, I HORAK, ID MARQUEZ, VE AF BURKE, TR FORD, H OSHEROV, N LEVITZKI, A STEFANOVA, I HORAK, ID MARQUEZ, VE TI ARYLAMIDES OF HYDROXYLATED ISOQUINOLINES AS PROTEIN-TYROSINE KINASE INHIBITORS SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID TYRPHOSTINS AB Aryl-substituted amides of isomeric 6,7- and 7,8-dihydroxyisoquinoline-3-carboxamides (2 and 3) were prepared. Divergent structural requirements were observed for inhibiting p56lck and epidermal growth factor receptor (EGFR) protein-tyrosine kinases (PTKs), with the 7,8-dihydroxy substitution pattern being essential for p56lck activity, and the arylamide being required for EGFR potency. The work presents a useful approach toward the design of inhibitors which can discriminate between different PTKs. C1 NCI,DIV CANC BIOL DIAG & CTR,METAB BRANCH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,DEPT BIOL CHEM,IL-91904 JERUSALEM,ISRAEL. RP BURKE, TR (reprint author), DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37,RM 5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 10 TC 15 Z9 15 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC PY 1992 VL 2 IS 12 BP 1771 EP 1774 DI 10.1016/S0960-894X(00)80473-4 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA KD889 UT WOS:A1992KD88900064 ER PT J AU HENDLER, RW WESTERHOFF, HV AF HENDLER, RW WESTERHOFF, HV TI REDOX INTERACTIONS IN CYTOCHROME-C-OXIDASE - FROM THE NEOCLASSICAL TOWARD MODERN MODELS SO BIOPHYSICAL JOURNAL LA English DT Article ID OXIDATION-REDUCTION POTENTIALS; HEME-HEME INTERACTION; BEEF-HEART; BINDING-SITES; LOW-SPIN; MITOCHONDRIA; SPECTRA; COPPER; ZINC; THERMODYNAMICS AB Because of recent experimental data on the redox characteristics of cytochrome c oxidase and renewed interest in the role of cooperativity in energy coupling, the question of redox cooperativity in cytochrome c oxidase is reexamined. Extensive redox cooperativity between more than two redox centers, some of which are spectrally invisible, may be expected for this electron transfer coupled proton pump. Such cooperativity, however, cannot be revealed by the traditional potentiometric experiments based on a difference in absorbance between two wavelengths. Multiwavelength analyses utilizing singular value decomposition and second derivatives of absorbance vs. wavelength have revealed a stronger cooperativity than consistent with the ''neoclassical'' model, which allowed only for weak negative cooperativity between two equipotential one-electron centers. A thermodynamic analysis of redox cooperativity is developed, which includes the possibilities of strong cooperative redox interactions, the involvement of invisible redox centers, conformational changes, and monomer/dimer equilibrations. The experimental observation of an oxidation of one of the cytochromes (a3) with a decrease in applied redox potential is shown to require both strong negative cooperativity and the participation of more than two one-electron centers. A number of ''modern'' models are developed using the analytical approaches described in this paper. By testing with experimental data, some of these models are falsified, whereas some are retained with suggestions for further testing. C1 UNIV AMSTERDAM,EC SLATER INST BIOCHEM RES,1066 CX AMSTERDAM,NETHERLANDS. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NETHERLANDS CANC INST,DIV MOLEC BIOL,1066 CX AMSTERDAM,NETHERLANDS. RI Westerhoff, Hans/I-5762-2012 OI Westerhoff, Hans/0000-0002-0443-6114 NR 52 TC 21 Z9 21 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 1992 VL 63 IS 6 BP 1586 EP 1604 PG 19 WC Biophysics SC Biophysics GA KF551 UT WOS:A1992KF55100018 PM 1336989 ER PT J AU DURELL, SR RAGHUNATHAN, G GUY, HR AF DURELL, SR RAGHUNATHAN, G GUY, HR TI MODELING THE ION CHANNEL STRUCTURE OF CECROPIN SO BIOPHYSICAL JOURNAL LA English DT Article ID INSECT IMMUNITY; ANTIBACTERIAL ACTIVITY; HYALOPHORA-CECROPIA; PERMEABLE CHANNELS; CRYSTAL-STRUCTURE; PEPTIDES; PROTEINS; PUPAE; PURIFICATION; ALAMETHICIN AB Atomic-scale computer models were developed for how cecropin peptides may assemble in membranes to form two types of ion channels. The models are based on experimental data and physiochemical principles. Initially, cecropin peptides, in a helix-bend-helix motif, were arranged as antiparallel dimers to position conserved residues of adjacent monomers in contact. The dimers were postulated to bind to the membrane with the NH2-terminal helices sunken into the head-group layer and the COOH-terminal helices spanning the hydrophobic core. This causes a thinning of the top lipid layer of the membrane. A collection of the membrane bound dimers were then used to form the type I channel structure, with the pore formed by the transmembrane COOH-terminal helices. Type I channels were then assembled into a hexagonal lattice to explain the large number of peptides that bind to the bacterium. A concerted conformational change of a type I channel leads to the larger type II channel, in which the pore is formed by the NH2-terminal helices. By having the dimers move together, the NH2-terminal helices are inserted into the hydrophobic core without having to desolvate the charged residues. It is also shown how this could bring lipid head-groups into the pore lining. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. NR 33 TC 62 Z9 65 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 1992 VL 63 IS 6 BP 1623 EP 1631 PG 9 WC Biophysics SC Biophysics GA KF551 UT WOS:A1992KF55100021 PM 1283347 ER PT J AU LEE, FJS MOSS, J LIN, LW AF LEE, FJS MOSS, J LIN, LW TI A SIMPLIFIED PROCEDURE FOR HYBRIDIZATION OF RNA BLOTS SO BIOTECHNIQUES LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP LEE, FJS (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. NR 4 TC 9 Z9 9 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1992 VL 13 IS 6 BP 844 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB620 UT WOS:A1992KB62000002 PM 1476734 ER PT J AU YONG, K SALOOJA, N DONAHUE, RE HEGDE, U LINCH, DC AF YONG, K SALOOJA, N DONAHUE, RE HEGDE, U LINCH, DC TI HUMAN MACROPHAGE COLONY-STIMULATING FACTOR LEVELS ARE ELEVATED IN PREGNANCY AND IN IMMUNE THROMBOCYTOPENIA SO BLOOD LA English DT Article ID TUMOR NECROSIS FACTOR; HUMAN MONOCYTE FUNCTION; FACTOR M-CSF; GROWTH-FACTOR; FACTOR-I; MURINE MACROPHAGES; IMMUNOGLOBULIN-G; FC-RECEPTORS; CELL-LINE; ENHANCEMENT C1 EALING GEN HOSP,DEPT HAEMATOL,LONDON,ENGLAND. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. RP YONG, K (reprint author), UNIV COLL & MIDDLESEX SCH MED,DEPT HAEMATOL,LONDON WC1E 6HX,ENGLAND. NR 45 TC 44 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 DEC 1 PY 1992 VL 80 IS 11 BP 2897 EP 2902 PG 6 WC Hematology SC Hematology GA KA482 UT WOS:A1992KA48200026 PM 1450415 ER PT J AU MURPHY, WJ DURUM, SK ANVER, M FRAZIER, M LONGO, DL AF MURPHY, WJ DURUM, SK ANVER, M FRAZIER, M LONGO, DL TI RECOMBINANT HUMAN GROWTH-HORMONE PROMOTES HUMAN LYMPHOCYTE ENGRAFTMENT IN IMMUNODEFICIENT MICE AND RESULTS IN AN INCREASED INCIDENCE OF HUMAN EPSTEIN-BARR VIRUS-INDUCED B-CELL LYMPHOMA SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article C1 NCI,FREDERICK CANC RES & DEV CTR,OFF ASSOCIATE DIRECTOR,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 15 TC 38 Z9 38 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 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD DEC PY 1992 VL 6 IS 4 BP 355 EP 364 DI 10.1016/0889-1591(92)90034-L PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA KE831 UT WOS:A1992KE83100004 PM 1336993 ER PT J AU HOUGE, G CHOCHUNG, YS DOSKELAND, SO AF HOUGE, G CHOCHUNG, YS DOSKELAND, SO TI DIFFERENTIAL EXPRESSION OF CAMP-KINASE SUBUNITS IS CORRELATED WITH GROWTH IN RAT MAMMARY CARCINOMAS AND UTERUS SO BRITISH JOURNAL OF CANCER LA English DT Article ID DEPENDENT PROTEIN-KINASE; I REGULATORY SUBUNIT; AMP BINDING-PROTEINS; HUMAN-BREAST CANCER; TISSUE-SPECIFIC EXTINGUISHER; DOG THYROID-CELLS; CYCLIC-AMP; CATALYTIC SUBUNIT; DNA-SYNTHESIS; ESTROGEN-RECEPTOR AB The expression of the regulatory (RI and RII) and catalytic (C) subunits of cAMP-dependent protein kinase was found to depend on the growth-state in oestrogen-dependent DMBA-induced mammary adenocarcinomas as well as in uteri of the rat. Castration-induced atrophy of the oestrogen-dependent tissues was accompanied by a decrease of the concentration of regulatory subunits (RI and RII) relative to both the catalytic subunit (C) and total protein, decreasing the R/protein and R/C ratios. A hyperplastic burst caused by high-dose oestrogen-replacement treatment was associated with an increased level of RI and little change in RII and C levels. Only minor differences were noted for the expression of mRNA for the alpha and beta subtypes of RI, RII and C between rat uteri from castrated and oestrogen-treated animals, or between mammary tumours from normal and castrated animals. Expression of RIbeta-mRNA was detected only in the uterus. Our findings provide an experimental correlate for the reported value of the parameter R/protein in human mammary cancer biopsies to predict prognosis and outcome of therapy. Due to the sensitivity of the R/protein ratio towards changes in extracellular protein content, we recommend the biologically more meaningful R/C ratio in further clinical evaluations of mammary tumour biopsies. C1 NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BETHESDA,MD 20890. RP HOUGE, G (reprint author), UNIV BERGEN,DEPT ANAT,CELL BIOL RES GRP,ARSTADV 19,N-5009 BERGEN,NORWAY. NR 60 TC 11 Z9 11 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC PY 1992 VL 66 IS 6 BP 1022 EP 1029 DI 10.1038/bjc.1992.404 PG 8 WC Oncology SC Oncology GA KC343 UT WOS:A1992KC34300006 PM 1457341 ER PT J AU HATCH, EE CURTIS, RE BOICE, JD FRAUMENI, JF AF HATCH, EE CURTIS, RE BOICE, JD FRAUMENI, JF TI MALIGNANT NEOPLASMS ASSOCIATED WITH CANCER OF THE AMPULLA OF VATER SO BRITISH JOURNAL OF CANCER LA English DT Letter RP HATCH, EE (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC PY 1992 VL 66 IS 6 BP 1204 EP 1204 DI 10.1038/bjc.1992.439 PG 1 WC Oncology SC Oncology GA KC343 UT WOS:A1992KC34300041 PM 1457366 ER PT J AU WELLER, M KORNHUBER, J AF WELLER, M KORNHUBER, J TI CLOZAPINE RECHALLENGE AFTER AN EPISODE OF NEUROLEPTIC MALIGNANT SYNDROME SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Note AB Nine out of 4044 patients admitted to our institution between 1987 and 1990 suffered an episode of NMS. Neuroleptic rechallenge using clozapine for persisting psychiatric illness was tolerated by eight patients. Clozapine was discontinued in one older, high-risk patient because recurrence of NMS was anticipated. Clozapine should be considered a drug of choice for psychotic patients with a history of NMS. C1 UNIV WURZBURG,DEPT PSYCHIAT,FUCHSLEINSTR 15,W-8700 WURZBURG,GERMANY. NIH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RI Kornhuber, Johannes/B-9613-2014 OI Kornhuber, Johannes/0000-0002-8096-3987 NR 10 TC 30 Z9 30 U1 0 U2 0 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD DEC PY 1992 VL 161 BP 855 EP 856 DI 10.1192/bjp.161.6.855 PG 2 WC Psychiatry SC Psychiatry GA KD543 UT WOS:A1992KD54300021 PM 1362370 ER PT J AU BROWN, M CHRISTIANSEN, J PHILIPS, P AF BROWN, M CHRISTIANSEN, J PHILIPS, P TI THE DECLINE OF CHILD LABOR IN THE UNITED-STATES FRUIT AND VEGETABLE CANNING INDUSTRY - LAW OR ECONOMICS SO BUSINESS HISTORY REVIEW LA English DT Article ID MECHANIZATION AB Child labor in the U.S. economy declined significantly between 1880 and 1920. This case study of the fruit and vegetable canning industry examines variations in laws, technology, and income across states and time to assess the relative importance of legal and economic factors in reducing the employment of children. The authors find that economic factors, especially a technologically driven shift toward a greater demand for adult labor, were relatively more important. While economic development was often a precondition for legal restrictions on child labor, compulsory schooling and child labor laws restricted the employment of children in technologically backward canneries. C1 MT HOLYOKE COLL,S HADLEY,MA 01075. UNIV UTAH,SALT LAKE CITY,UT 84112. RP BROWN, M (reprint author), NCI,APPL RES BRANCH,BETHESDA,MD 20892, USA. NR 50 TC 14 Z9 14 U1 1 U2 6 PU BUSINESS HISTORY REVIEW PI BOSTON PA TEELE HALL 304 HARVARD BUS SCH PUBL SOLDIERS FIELD, BOSTON, MA 02163-0014 SN 0007-6805 J9 BUS HIST REV JI Bus. Hist. Rev. PD WIN PY 1992 VL 66 IS 4 BP 723 EP 770 DI 10.2307/3116845 PG 48 WC Business; History Of Social Sciences SC Business & Economics; Social Sciences - Other Topics GA MH719 UT WOS:A1992MH71900003 ER PT J AU KANT, AK GLOVER, C HORM, J SCHATZKIN, A HARRIS, TB AF KANT, AK GLOVER, C HORM, J SCHATZKIN, A HARRIS, TB TI DOES CANCER SURVIVAL DIFFER FOR OLDER PATIENTS SO CANCER LA English DT Article DE AGE; CANCER SURVIVAL; ELDERLY; STAGE AT DIAGNOSIS ID END RESULTS PROGRAM; BREAST-CANCER; AGE; DIAGNOSIS; SURVEILLANCE; EPIDEMIOLOGY; VARIES; STAGE; CARE AB The relation of age to 5-year relative survival rates was examined for leading sites of cancer resulting in death among 127,554 patients; data from 1978 to 1982 were studied for four areas of the Surveillance, Epidemiology and End Results program of the National Cancer Institute. Overall and stage-stratified relative survival rates declined with advancing patient age for cancer of the lung, prostate, pancreas, bladder, oral cavity, uterus, cervix, ovary, and large bowel (women only). In men, this trend was not explained by age differences in stage of diagnosis, whereas, among women, age was associated with more advanced disease for most sites examined. Although overall survival rates were lower in black patients compared with white patients, the age-survival and age-stage trends were similar in the two racial groups. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NATL CTR HLTH STAT,DIV HLTH INTERVIEW STAT,HYATTSVILLE,MD 20782. NIA,GERIATR EPIDEMIOL OFF,BETHESDA,MD 20892. RP KANT, AK (reprint author), CUNY QUEENS COLL,DIV MATH & NAT SCI,REMSEN HALL,ROOM 306E,65-30 KISSENA BLVD,FLUSHING,NY 11367, USA. NR 23 TC 36 Z9 36 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 DEC 1 PY 1992 VL 70 IS 11 BP 2734 EP 2740 DI 10.1002/1097-0142(19921201)70:11<2734::AID-CNCR2820701127>3.0.CO;2-F PG 7 WC Oncology SC Oncology GA JY880 UT WOS:A1992JY88000026 PM 1423205 ER PT J AU ROBINSON, K BARG, FK MCCORKLE, R YASKO, JM JEPSON, C VOGT, C MCKEEHAN, KM DEININGER, H AF ROBINSON, K BARG, FK MCCORKLE, R YASKO, JM JEPSON, C VOGT, C MCKEEHAN, KM DEININGER, H TI GAPS AND CONTRACT - EVALUATING THE DIFFUSION OF NEW INFORMATION .2. THE MEASUREMENT OF THE STRATEGY SO CANCER NURSING LA English DT Article DE INFORMATION; EVALUATION; DIFFUSION; CONTRACT; STRATEGY AB This article is the second of a two-part series describing ''gaps and contract,'' a strategy that provides nurses with a mechanism to transfer knowledge from theory into practice in a measurable format. Two universities under contract from the Pennsylvania state cancer plan used this strategy to evaluate the effectiveness of a cancer continuing education program. Two hundred seventy-four (274) contracts from one setting and 205 from a second setting are described. Recommendations for using this strategy to measure the efficacy of cancer continuing education programs are included. C1 UNIV PENN,SCH NURSING,CTR ADV CARE SERIOUS ILLNESS,ROOM 347,PHILADELPHIA,PA 19104. UNIV PITTSBURGH,CANC INFORMAT & REFERRAL SERV,PITTSBURGH,PA 15260. UNIV PITTSBURGH,PITTSBURGH CANC INST,PAIR,PITTSBURGH,PA 15260. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. PAIR,PHILADELPHIA,PA. UNIV PITTSBURGH,SCH NURSING,PITTSBURGH,PA 15260. PITTSBURGH CANC INST,DIV NURSING & PATIENT CARE SERV,PITTSBURGH,PA. HAMOT MED CTR,ERIE,PA. NCI,INT CANC INFORMAT CTR,BETHESDA,MD 20892. NR 7 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD DEC PY 1992 VL 15 IS 6 BP 406 EP 414 PG 9 WC Oncology; Nursing SC Oncology; Nursing GA KD260 UT WOS:A1992KD26000004 PM 1473084 ER PT J AU CARROLL, R GREEN, J LAKE, P LEVY, W SHIVES, B AF CARROLL, R GREEN, J LAKE, P LEVY, W SHIVES, B TI PROGRAMMED-INSTRUCTION - CANCER CARE - BASIC CANCER CONCEPTS SO CANCER NURSING LA English DT Article C1 NCI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. RP CARROLL, R (reprint author), ST LUKES ROOSEVELT HOSP,DEPT NURSING EDUC DEV & RES,NEW YORK,NY 10025, USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD DEC PY 1992 VL 15 IS 6 BP 437 EP 451 PG 15 WC Oncology; Nursing SC Oncology; Nursing GA KD260 UT WOS:A1992KD26000008 PM 1473088 ER PT J AU CONWAY, K MORGAN, D PHILLIPS, KK YUSPA, SH WEISSMAN, BE AF CONWAY, K MORGAN, D PHILLIPS, KK YUSPA, SH WEISSMAN, BE TI TUMORIGENIC SUPPRESSION OF A HUMAN CUTANEOUS SQUAMOUS-CELL CARCINOMA CELL-LINE IN THE NUDE-MOUSE SKIN-GRAFT ASSAY SO CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; DINUCLEOTIDE REPEAT POLYMORPHISMS; MEDIATED CHROMOSOME TRANSFER; WILMS TUMOR LOCUS; CYSTIC-FIBROSIS; GENE; ONCOGENE; DELETIONS; IDENTIFICATION; EXPRESSION AB The development of human squamous cell carcinomas has been associated with a number of genetic alterations involving chromosome 11, including cytogenetic and allelic deletions as well as amplification of genes in the 11q13 region. To determine the relevance of chromosome 11 in the formation of tumors of stratified squamous epithelial origin, we have introduced, via microcell fusion, a normal human chromosome 11 into the cutaneous squamous cell carcinoma cell line A3886TGc2. The ability of chromosome 11 to modulate the tumorigenicity of A3886TGc2 was evaluated first by inoculating cells s.c. in nude mice. All hybrids remained tumorigenic but exhibited longer tumor latencies than the parent, a result previously observed by other laboratories. We then tested our epidermally derived hybrids in the more physiologically relevant environment of the nude mouse skin graft system. The tumorigenic phenotype of three of four chromosome 11 hybrids placed into nude mouse skin grafts was completely suppressed. Polymerase chain reaction amplification of DNA from normal skin present at the suppressed graft sites failed to detect the introduced human cells. This information indicates that the normal skin is of mouse origin and suggests that the chromosome 11 microcell hybrids did not differentiate in vivo, but most likely failed to survive. We propose that external environmental factors present at the site of inoculation modulate the tumorigenic potential of these cells. C1 UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,LINEBERGER COMPRHENS CANC CTR,CHAPEL HILL,NC 27599. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [5F 32 CA09015-02] NR 56 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1992 VL 52 IS 23 BP 6487 EP 6495 PG 9 WC Oncology SC Oncology GA JZ430 UT WOS:A1992JZ43000010 PM 1358434 ER PT J AU MARINCOLA, FM VENZON, D WHITE, D RUBIN, JT LOTZE, MT SIMONIS, TB BALKISSOON, J ROSENBERG, SA PARKINSON, DR AF MARINCOLA, FM VENZON, D WHITE, D RUBIN, JT LOTZE, MT SIMONIS, TB BALKISSOON, J ROSENBERG, SA PARKINSON, DR TI HLA ASSOCIATION WITH RESPONSE AND TOXICITY IN MELANOMA PATIENTS TREATED WITH INTERLEUKIN 2-BASED IMMUNOTHERAPY SO CANCER RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; FAMILIAL MALIGNANT-MELANOMA; DR ANTIGEN EXPRESSION; INFILTRATING LYMPHOCYTES; FACTOR-ALPHA; CANCER-PATIENTS; CLINICAL COURSE; FACTOR-BETA; T-CELLS AB Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), alpha-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of All (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT SURG,PITTSBURGH,PA 15261. RP MARINCOLA, FM (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,SURG BRANCH,BLDG 10,ROOM 2342,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 47 TC 54 Z9 55 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1992 VL 52 IS 23 BP 6561 EP 6566 PG 6 WC Oncology SC Oncology GA JZ430 UT WOS:A1992JZ43000021 PM 1423301 ER PT J AU YEH, GC LOPACZYNSKA, J POORE, CM PHANG, JM AF YEH, GC LOPACZYNSKA, J POORE, CM PHANG, JM TI A NEW FUNCTIONAL-ROLE FOR P-GLYCOPROTEIN - EFFLUX PUMP FOR BENZO(A)PYRENE IN HUMAN BREAST-CANCER MCF-7 CELLS SO CANCER RESEARCH LA English DT Note ID MULTIDRUG-RESISTANT CELLS; MEMBRANE GLYCOPROTEIN; VINBLASTINE; XENOBIOTICS; TRANSPORT; VERAPAMIL; VESICLES; LIVER AB We propose that the cellular burden of certain carcinogens may be mitigated by P-glycoprotein (P-gp), the putative drug efflux pump. In a series of multidrug resistant human breast cancer MCF-7 cells with increasing P-gp expression we examined this hypothesis using benzo(a)pyrene, a widely distributed environmental and dietary carcinogen. We found that multidrug resistant cells were cross-resistant to benzo(a)pyrene and the rates of efflux for benzo(a)pyrene were higher in multidrug resistant cells than in wild type cells. Evidence supporting the involvement of P-gp included the inhibition of azidopine binding to P-gp benzo(a)pyrene and the inhibition of benzo(a)pyrene efflux by Adriamycin and verapamil. Our findings suggest that P-gp may play a role in the cellular defense to carcinogens. The expression of P-gp and the modulation of its function may affect the susceptibility of normal tissues to transformation by carcinogens. RP YEH, GC (reprint author), NCI,FCRDC,DIV CANC PREVENT & CONTROL,LNMR,BLDG 560,ROOM 12-48,FREDERICK,MD 21702, USA. NR 23 TC 94 Z9 94 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1992 VL 52 IS 23 BP 6692 EP 6695 PG 4 WC Oncology SC Oncology GA JZ430 UT WOS:A1992JZ43000042 PM 1358437 ER PT J AU KATO, S SHIELDS, PG CAPORASO, NE HOOVER, RN TRUMP, BF SUGIMURA, H WESTON, A HARRIS, CC AF KATO, S SHIELDS, PG CAPORASO, NE HOOVER, RN TRUMP, BF SUGIMURA, H WESTON, A HARRIS, CC TI CYTOCHROME-P450IIE1 GENETIC POLYMORPHISMS, RACIAL VARIATION, AND LUNG-CANCER RISK SO CANCER RESEARCH LA English DT Note ID DNA; DEBRISOQUINE; SUSCEPTIBILITY; SENSITIVITY; METABOLISM; OXIDATION AB Cytochrome P450IIE1 is responsible for the activation of carcinogenic N-nitrosamines, benzene, urethane, and other low-molecular-weight compounds. Restriction fragment length polymorphisms (PstI and RsaI restriction enzymes) have been identified in the cytochrome P45011E1 transcription regulatory region that may affect expression. This study describes the PstI and RsaI polymorphisms in different racial populations and in a case-control study of lung cancer. The allelic frequencies were markedly different in Japanese, African-Americans, and Caucasians: the PstI rare allele was present at a frequency of 2% in Caucasians, 5% in African-Americans, and 24% in Japanese (P < 0.05). For the RsaI rare allele, frequencies were 2% in Caucasians, 2% in African-Americans, and 27% in Japanese (P < 0.05). The assay was also applied to 128 individuals enrolled in a case-control study of lung cancer. Although limited in statistical power, the data indicate no evidence for an association in the aggregate of cytochrome P450IIE1 PstI [for which the odds ratio was 0.7 (95% confidence interval (C.I.) = 0.2-2.8)] or RsaI [for which the odds ratio was 0.9 (95% C.I. = 0.2-5.4)] restriction fragment length polymorphisms with lung cancer in this U.S. population. When analyzed by race, the lung cancer odds ratio for the PstI mutant allele in African-Americans was 0.19 (95% C.I. = 0.03-1.38), and in Caucasians it was 4.13 (95% C.I. = 0.34-48.8). For the RsaI mutant allele, the odds ratios were 0.20 (95% C.I. = 0.02-2.43) and 4.28 (95% C.I. = 0.35-50.6), respectively. The ethnic differences of these restriction fragment length polymorphisms might be related to genetic susceptibilities for lung cancer among Caucasians and for gastric or esophageal cancer among Japanese. C1 NCI, DIV CANC ETIOL, HUMAN CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. NCI, DIV CANC ETIOL, ENVIRONM EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. UNIV MARYLAND, DEPT PATHOL, BALTIMORE, MD 21201 USA. HAMAMATSU UNIV SCH MED, DEPT PATHOL 1, HAMAMATSU, SHIZUOKA 43131, JAPAN. NR 32 TC 184 Z9 192 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1992 VL 52 IS 23 BP 6712 EP 6715 PG 4 WC Oncology SC Oncology GA JZ430 UT WOS:A1992JZ43000048 PM 1423319 ER PT J AU HRUSZKEWYCZ, A CANELLA, KA PELTONEN, K KOTRAPPA, L DIPPLE, A AF HRUSZKEWYCZ, A CANELLA, KA PELTONEN, K KOTRAPPA, L DIPPLE, A TI DNA-POLYMERASE ACTION ON BENZO[A]PYRENE-DNA ADDUCTS SO CARCINOGENESIS LA English DT Article ID OPTICAL ENANTIOMERS; DIHYDRODIOL EPOXIDE; DIOL-EPOXIDE; MOUSE SKIN; 7,8-DIOL-9,10-EPOXIDES; DEOXYGUANOSINE; DEOXYADENOSINE; BINDING; TERMINATION; ADJACENT AB A 16mer oligonucleotide containing a single guanine residue at nucleotide 13 from the 3' end was treated with the (+)-enantiomer of the 7,8-dihydrodiol 9,10-epoxide of benzo[a]pyrene (B[a]P). Oligonucleotides containing either an adduct in which the epoxide ring was opened trans or cis by the amino group of the guanine residue were separated by chromatography and identified by P-32 postlabeling and circular dichroism spectroscopy. In the presence of nucleotide triphosphates and DNA polymerase (either Sequenase, version 2.0 or human polymerase alpha), it was found that the B[a]P adducts inhibited extension of an 11mer primer opposite the nucleotide 3' to the adduct in the template. Under various conditions, this inhibition was greater for the cis adduct than for the trans adduct. After a 10 min incubation with Sequenase, primer extension was reduced to approximately 20% of that seen with unmodified oligonucleotide by the trans adduct and was almost completely inhibited by the cis adduct. When a 12mer primer was used to examine nucleotide incorporation directly across from the guanine or adducted guanine residues, it was clear that deoxycytidylic acid was preferentially incorporated in all cases but that the incorporation was severely inhibited by both the cis and trans adducts. These findings suggest that a cis adduct is a more effective block to replication than a trans adduct, and that these adducts may not be very efficient mutagenic lesions. RP HRUSZKEWYCZ, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 27 TC 72 Z9 72 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1992 VL 13 IS 12 BP 2347 EP 2352 DI 10.1093/carcin/13.12.2347 PG 6 WC Oncology SC Oncology GA KD322 UT WOS:A1992KD32200025 PM 1473243 ER PT J AU LEE, E PUNNONEN, K CHENG, C GLICK, A DLUGOSZ, A YUSPA, SH AF LEE, E PUNNONEN, K CHENG, C GLICK, A DLUGOSZ, A YUSPA, SH TI ANALYSIS OF PHOSPHOLIPID-METABOLISM IN MURINE KERATINOCYTES TRANSFORMED BY THE V-RAS ONCOGENE - RELATIONSHIP OF PHOSPHATIDYLINOSITOL TURNOVER AND CYTOKINE STIMULATION TO THE TRANSFORMED PHENOTYPE SO CARCINOGENESIS LA English DT Article ID PROTEIN-KINASE-C; MOUSE EPIDERMAL-CELLS; INOSITOL PHOSPHATE-METABOLISM; ESTER TUMOR PROMOTERS; TERMINAL DIFFERENTIATION; TGF-ALPHA; PHOSPHATIDYLCHOLINE BREAKDOWN; DIACYLGLYCEROL PRODUCTION; QUANTITATIVE MEASUREMENT; ADENYLATE-CYCLASE AB Introduction of a v-ras(Ha) oncogene into cultured mouse keratinocytes by transduction with a defective retrovirus is sufficient to transform keratinocytes to the benign phenotype. Transduced keratinocytes overexpress TGFalpha and hyperproliferate in culture medium with 0.05 mM Ca2+. Whereas normal keratinocytes respond to elevated medium Ca2+ by cessation of proliferation and induction of terminal differentiation, v-ras(Ha) keratinocytes are not induced to differentiate by Ca2+. We now demonstrate that v-ras(Ha) keratinocytes have elevated basal levels of phosphatidylinositol, inositol phosphates and diacylglycerols in 0.05 mM Ca2+ medium. Basal turnover of phosphatidylcholine is not altered by the ras(Ha) oncogene. The generation of inositol phosphates is even further stimulated in v-ras(Ha) cells by an increase in extracellular Ca2+ or by exposure to aluminum fluoride. Thus, the v-ras(Ha) gene product does not stimulate the inositol phospholipid pathway maximally and additional phosphatidylinositol is available for turnover in response to inducers of phospholipase C activity. TGFalpha and medium conditioned by v-ras(Ha) keratinocytes, both of which stimulate proliferation of normal cells in 0.05 mM Ca2+, transiently increased phosphatidylinositol turnover in normal keratinocytes but did not inhibit Ca2+-induced terminal differentiation. In contrast, sustained elevation in basal phosphatidylinositol metabolism was produced by aluminum fluoride. Combined exposure to aluminum fluoride and exogenous TGFalpha caused hyperproliferation, resistance to Ca2+-induced differentiation and morphological changes identical to those of v-ras(Ha) keratinocytes. These results provide a link between the biological consequences of v-ras(Ha) gene expression and biochemical changes which are known to alter the keratinocyte phenotype. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. RP YUSPA, SH (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NR 53 TC 23 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1992 VL 13 IS 12 BP 2367 EP 2373 DI 10.1093/carcin/13.12.2367 PG 7 WC Oncology SC Oncology GA KD322 UT WOS:A1992KD32200028 PM 1473246 ER PT J AU STANLEY, LA DEVEREUX, TR FOLEY, J LORD, PG MARONPOT, RR ORTON, TC ANDERSON, MW AF STANLEY, LA DEVEREUX, TR FOLEY, J LORD, PG MARONPOT, RR ORTON, TC ANDERSON, MW TI PROTOONCOGENE ACTIVATION IN LIVER-TUMORS OF HEPATOCARCINOGENESIS-RESISTANT STRAINS OF MICE SO CARCINOGENESIS LA English DT Article ID HA-RAS PROTOONCOGENE; C57BL/6J MALE-MICE; C3H-HEJ MALE-MICE; C-KI-RAS; ETHYL CARBAMATE; VINYL CARBAMATE; B6C3F1 MOUSE; N-NITROSODIETHYLAMINE; V-RAF; MUTATIONS AB Activation of the ras family of oncogenes occurs frequently in liver tumors of the B6C3F1 mouse, a strain which is highly sensitive to hepatocarcinogenesis. Many other mouse strains are much more resistant to hepatocarcinogenesis; the aim of this study was to determine the frequency and pattern of oncogene activation in spontaneous and chemically induced liver tumors of three such strains, the C57BL/6J, the C57BL/6 x DBA/2 F1 hybrid (B6D2F1) and the C57BL/6 x Balb/c F1 hybrid (B6BCF1). The C57BL/6, DBA/2 and Balb/c strains are all relatively resistant to spontaneous hepatocarcinogenesis (1.5-3.6% of animals develop liver tumors in 2 years); with regard to chemically induced hepatocarcinogenesis the Balb/c is highly resistant, the C57BL/6 has low susceptibility and the DBA/2 has low to moderate susceptibility. The nude mouse tumorigenicity assay was used to search for activated oncogenes in 15 C57BL/6J liver tumors induced by a single neonatal dose of vinyl carbamate (VC, 0.15 mumol/g body weight). Three tumors contained H-ras genes activated by point mutations at codon 61 and one contained a non-ras oncogene. The polymerase chain reaction and allele-specific oligonucleotide hybridization were used to study H-ras mutations in spontaneous and VC-induced tumors from all three strains of mice. The frequency of H-ras codon 61 mutations in tumors induced by 0.15 mumol/g body weight VC in the C57BL/6J mouse (5/37) was similar to that in spontaneous tumors (2/9); surprisingly, tumors induced by a lower dose of VC (0.03 mumol/g body weight) had a higher frequency of H-ras mutations (12/28). The frequencies of H-ras activation detected in VC (0.03 muml/g body weight)-induced tumors from the two F1 hybrids studied differed markedly. Only one VC-induced B6BCF1 tumor contained a mutated H-ras gene (1/10), whereas the majority of B6D2F1 tumors contained such mutations (23/33). Several spontaneous B6D2F1 liver tumors contained H-ras codon 61 mutations (6/15). Thus, H-ras activation frequency does not determine susceptibility to hepatocarcinogenesis in inbred mice and their Fl hybrids, since a relatively high frequency of H-ras mutations was observed in two resistant strains and a low frequency was found in the other strain. C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. ICI PHARMACEUT PLC,MACCLESFIELD SK10 4GT,CHESHIRE,ENGLAND. RP ANDERSON, MW (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 42 TC 30 Z9 30 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 DEC PY 1992 VL 13 IS 12 BP 2427 EP 2433 DI 10.1093/carcin/13.12.2427 PG 7 WC Oncology SC Oncology GA KD322 UT WOS:A1992KD32200037 PM 1361883 ER PT J AU LAKSO, M STEEG, PS WESTPHAL, H AF LAKSO, M STEEG, PS WESTPHAL, H TI EMBRYONIC EXPRESSION OF NM23 DURING MOUSE ORGANOGENESIS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID NUCLEOSIDE DIPHOSPHATE KINASE; HUMAN BREAST-CANCER; TUMOR-METASTASIS; DROSOPHILA DEVELOPMENT; GOOD PROGNOSIS; GENE; CELLS; DIFFERENTIATION; RESPONSIVENESS; MORPHOGENESIS AB Nonmetastatic (nm) 23 gene expression correlates inversely with metastatic potential in several rodent tumor model systems as well as in human infiltrating ductal breast and hepatocellular carcinomas. Since tumor cell invasion and metastasis involve many processes exhibited by normal cells during development, we investigated whether nm23 is expressed during mouse embryogenesis. Northern blot analysis of embryonic RNAs showed that nm23 gene transcription occurs widely during embryogenesis. Immunohistochemical analysis demonstrated that, at the onset of organogenesis, the amount of Nm23 protein is relatively low and uniform throughout the embryo. On embryonic day E10.5, the protein begins to accumulate preferentially in the developing nervous system and heart, the first embryonic tissues to differentiate. Subsequent differentiation of liver, kidney, skin, intestine, adrenal, and stomach (but not lung) epithelial cells during embryonic development is accompanied by increased Nm23 protein expression. Although most tissues retain Nm23 protein levels to adult life, the increase is transient in intestinal epithelia and cyclic in adult mammary tissue during pregnancy and lactation. We conclude that Nm23 protein accumulation is coincident with the functional differentiation of multiple epithelial tissues in the developing mouse. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP LAKSO, M (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BLDG 6B,ROOM 2B-211,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 96 Z9 99 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1992 VL 3 IS 12 BP 873 EP 879 PG 7 WC Cell Biology SC Cell Biology GA KB260 UT WOS:A1992KB26000003 PM 1472467 ER PT J AU NAZARALI, AJ REYNOLDS, GP AF NAZARALI, AJ REYNOLDS, GP TI MONOAMINE NEUROTRANSMITTERS AND THEIR METABOLITES IN BRAIN-REGIONS IN ALZHEIMERS-DISEASE - A POSTMORTEM STUDY SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE ALZHEIMERS DISEASE; POSTMORTEM BRAIN; NEUROTRANSMITTERS; CATECHOLAMINES; INDOLEAMINES; ACID METABOLITES ID SENILE DEMENTIA; LOCUS-COERULEUS; SELECTIVE LOSS; CHOLINERGIC NEURONS; BIOGENIC-AMINES; CEREBRAL-CORTEX; DOPAMINE; DEFICITS; NORADRENALINE; SOMATOSTATIN AB 1. Concentrations of the neurotransmitter amines noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) and the acid metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in four regions of postmortem brains of demented patients with or without Alzheimer's disease (AD). 2. NA was deficient in the temporal cortex (BA 21) of AD, but not of non-AD, patients. 3. Caudate, in particular, had an impaired dopaminergic system in AD patients, with low HVA levels. 4. In all regions investigated [amygdala, caudate, putamen, temporal cortex (BA 21)] 5-HT was significantly depleted in AD patients, and 5-HIAA was also depleted in amygdala and caudate. 5. These results indicate that neurotransmitter systems other than cholinergic systems are also widely affected in AD and suggest that these deficits may also play an important role in determining the symptomatology of AD. C1 QUEENS MED CTR,DEPT PATHOL,NOTTINGHAM NG7 2UH,ENGLAND. RP NAZARALI, AJ (reprint author), NHLBI,BIOCHEM GENET LAB,NIH BLDG 36,ROOM 1C-06,BETHESDA,MD 20892, USA. OI Reynolds, Gavin/0000-0001-9026-7726 NR 37 TC 64 Z9 65 U1 1 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD DEC PY 1992 VL 12 IS 6 BP 581 EP 587 DI 10.1007/BF00711237 PG 7 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA KA524 UT WOS:A1992KA52400006 PM 1283363 ER PT J AU HOFFMAN, AGD LAWRENCE, MG OGNIBENE, FP SUFFREDINI, AF LIPSCHIK, GY KOVACS, JA MASUR, H SHELHAMER, JH AF HOFFMAN, AGD LAWRENCE, MG OGNIBENE, FP SUFFREDINI, AF LIPSCHIK, GY KOVACS, JA MASUR, H SHELHAMER, JH TI REDUCTION OF PULMONARY SURFACTANT IN PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION AND PNEUMOCYSTIS-CARINII PNEUMONIA SO CHEST LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; BRONCHOALVEOLAR LAVAGE; CONTROLLED TRIAL; FLUID; PHOSPHOLIPASE-A2; CORTICOSTEROIDS; ABNORMALITIES; DIAGNOSIS; FAILURE AB We assessed qualitative and quantitative differences in surfactant lipid composition of bronchoalveolar lavage (BAL) fluid in patients with acquired immune deficiency syndrome (AIDS) and Pneumocystis carinii (PC) pneumonia. Five normal volunteers and 27 patients with human immunodeficiency virus (HIV) infection underwent BAL for evaluation of possible pulmonary infection. Bronchoalveolar lavage studies in eight patients were negative for PC organisms, and 19 were positive. Pneumocystis carinii pneumonia was graded (mild vs moderate to severe) by initial alveolar-arterial oxygen gradient. Bronchoalveolar lavage fluid was centrifuged, the lipids were extracted from the supernatant, and total lipid profiles of dephosphorylated glycerolipids were analyzed as trimethylsilylether derivatives by high temperature gas-liquid chromatography. Phospholipase A2 levels were determined using a radiolabeled E coli membrane method. Compared to the normal volunteers (109+/-13 mug/5 ml) and the PC negative group (107+/-13 mug/5 ml), total BAL lipid was reduced for both the mild PC pneumonia group (73-10 mug/5 ml) and the moderate to severe PC pneumonia group (46+/-4 mug/5 ml). There was a parallel reduction of diacylglycerol lipids: normal volunteers, 52+/-7 mug/5 ml; PC negative, 52+/-9 mug/5 ml; mild PC pneumonia, 35+/-7 mug/5 ml; and moderate to severe PC pneumonia, 15+/-2 mug/5 ml. Phospholipase A2 activity in moderate to severe PC pneumonia was twice that of the PC negative patients, and 30 times that for normals. The data demonstrate a marked diminution in surfactant glycerophospholipid in patients with AIDS and PC pneumonia and suggest a potential role for surfactant abnormality in the pathophysiology of this disease. RP HOFFMAN, AGD (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BLDG 10,RM 7D43,BETHESDA,MD 20892, USA. NR 28 TC 61 Z9 62 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1992 VL 102 IS 6 BP 1730 EP 1736 DI 10.1378/chest.102.6.1730 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA KB485 UT WOS:A1992KB48500021 PM 1446480 ER PT J AU EMDE, RN PLOMIN, R ROBINSON, J CORLEY, R DEFRIES, J FULKER, DW REZNICK, JS CAMPOS, J KAGAN, J ZAHNWAXLER, C AF EMDE, RN PLOMIN, R ROBINSON, J CORLEY, R DEFRIES, J FULKER, DW REZNICK, JS CAMPOS, J KAGAN, J ZAHNWAXLER, C TI TEMPERAMENT, EMOTION, AND COGNITION AT 14 MONTHS - THE MACARTHUR LONGITUDINAL TWIN STUDY SO CHILD DEVELOPMENT LA English DT Article ID GENOTYPE-ENVIRONMENT INTERACTION; BEHAVIORAL-INHIBITION; CHILDHOOD; PERSONALITY; CHILDREN; INFANCY AB 200 pairs of twins were assessed at 14 months of age in the laboratory and home. Measures were obtained of temperament, emotion, and cognition/language. Comparisons between identical and fraternal twin CorrelationS suggest that individual differences are due in part to heritable influences. For temperament, genetic influence was significant for behavioral observations of inhibition to the unfamiliar, tester ratings of activity, and parental ratings of temperament. For emotion, significant genetic influence was found for empathy and parental ratings of negative emotion. The estimate of heritability for parental report of expression of negative emotions was relatively high, whereas that for expression of positive emotionS was low, a finding consistent with previous research. For cognition and language, genetic influence was significant for behavioral indices of spatial memory, categorization, and word comprehension. Shared rearing environment appears influential for parental reports of language and for positive emotions, but not for other measures of emotion or for temperament. C1 PENN STATE UNIV,UNIV PK,PA 16802. UNIV COLORADO,BOULDER,CO 80309. YALE UNIV,NEW HAVEN,CT 06520. UNIV CALIF BERKELEY,BERKELEY,CA 94720. HARVARD UNIV,CAMBRIDGE,MA 02138. NIMH,BETHESDA,MD 20892. RP EMDE, RN (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,4200 E 9TH AVE,DENVER,CO 80262, USA. RI Plomin, Robert/B-8911-2008 FU NIMH NIH HHS [5 K02 MH36808] NR 59 TC 133 Z9 135 U1 2 U2 14 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD DEC PY 1992 VL 63 IS 6 BP 1437 EP 1455 DI 10.1111/j.1467-8624.1992.tb01706.x PG 19 WC Psychology, Educational; Psychology, Developmental SC Psychology GA JY288 UT WOS:A1992JY28800011 PM 1446561 ER PT J AU PAULY, RR PASSANITI, A CROW, M KINSELLA, JL PAPADOPOULOS, N MONTICONE, R LAKATTA, EG MARTIN, GR AF PAULY, RR PASSANITI, A CROW, M KINSELLA, JL PAPADOPOULOS, N MONTICONE, R LAKATTA, EG MARTIN, GR TI EXPERIMENTAL-MODELS THAT MIMIC THE DIFFERENTIATION AND DEDIFFERENTIATION OF VASCULAR CELLS SO CIRCULATION LA English DT Article DE CELLS, ENDOTHELIAL; CELLS, VASCULAR SMOOTH MUSCLE; DIFFERENTIATION; EXTRACELLULAR MATRIX ID CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR; REGULATORY FACTORS; GENE; EXPRESSION; INDUCTION; LAMININ; ANGIOGENESIS AB Endothelial and smooth muscle cells normally exist in a quiescent differentiated state. After injury to the vessel, these cells dedifferentiate, migrate, and proliferate as needed for repair. In culture on plastic, both endothelial and smooth muscle cells exhibit the dedifferentiated phenotype. We have found that laminin and reconstituted basement membrane proteins (Matrigel) induce a very rapid cessation of endothelial cell proliferation followed by alignment and subsequent reorganization into tubelike structures. We have also found that smooth muscle cells in culture exhibit a differentiated phenotype when exposed to Matrigel. The molecular mechanisms involved in smooth muscle differentiation resemble those of skeletal muscle, in which proliferation and differentiation appear to be mutually exclusive states controlled by both positive and negative transcriptional regulators. The dedifferentiated smooth muscle cells produce proteases and exhibit a migratory and invasive phenotype capable of destroying normal tissue architecture. These studies suggest that the modulation of endothelial and smooth muscle cells between a differentiated and dedifferentiated phenotype is regulated by extracellular matrix components as well as by cytokines. Model systems such as those described here should allow the identification of molecular events controlling the differentiation of vascular cells and facilitate the development of therapeutic agents that maintain healthy vessels. RP PAULY, RR (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Papadopoulos, Nickolas/K-7272-2012 NR 21 TC 80 Z9 81 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1992 VL 86 IS 6 SU S BP 68 EP 73 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KB721 UT WOS:A1992KB72100010 ER PT J AU ELLIS, SG SAVAGE, M FISCHMAN, D BAIM, DS LEON, M GOLDBERG, S HIRSHFELD, JW CLEMAN, MW TEIRSTEIN, PS WALKER, C BAILEY, S BUCHBINDER, M TOPOL, EJ SCHATZ, RA AF ELLIS, SG SAVAGE, M FISCHMAN, D BAIM, DS LEON, M GOLDBERG, S HIRSHFELD, JW CLEMAN, MW TEIRSTEIN, PS WALKER, C BAILEY, S BUCHBINDER, M TOPOL, EJ SCHATZ, RA TI RESTENOSIS AFTER PLACEMENT OF PALMAZ-SCHATZ STENTS IN NATIVE CORONARY-ARTERIES - INITIAL RESULTS OF A MULTICENTER EXPERIENCE SO CIRCULATION LA English DT Article DE ANGIOPLASTY, CORONARY; STENTS; RESTENOSIS ID EXPANDABLE INTRACORONARY STENTS; ANGIOGRAPHIC FOLLOW-UP; INTRAVASCULAR STENTS; PREVENT RESTENOSIS; 2ND RESTENOSIS; GROWTH-FACTORS; ANGIOPLASTY; ATHERECTOMY; PTCA; DETERMINANTS AB Background. Several metallic intracoronary stents axe currently undergoing preliminary evaluation to ascertain potential benefit as means to reduce the 30-40% incidence of restenosis after balloon angioplasty. Methods and Results. To determine the incidence and correlates of restenosis after placement of Palmaz-Schatz stents in native coronary arteries in the first group of patients selected for this clinical and quantitative angiographic data from 206 consecutive patients (221 stenoses) with successful stent placement (diameter stenosis <50%) were analyzed. Six patients (2.9%) had thrombosis-mediated stent closure within 1 month after stent placement and were excluded from long-term angiographic follow-up. One hundred eighty-one (91%) of the remaining 200 patients had angiography at 5.8 +/- 2.1 months. Patients with and without follow-up did not differ in any baseline characteristic; in particular history of restenosis at the site stented (73% versus 65%), placement of multiple overlapping stents (17% versus 20%), and mean poststent diameter stenosis (16 +/- 12% versus 14 +/- 12%). The overall incidence of restenosis (diameter stenosis greater-than-or-equal-to 50% at follow-up) in this group at high risk for restenosis was 36% (95% confidence interval, 29-43%) on a per-stenosis basis. The incidence of restenosis when a single stent was placed was 30% (95% confidence interval, 23-37%). Risk was dependent upon a history of restenosis (present versus absent 36% versus 16%, p=0.02) and upon whether or not a poststent stenosis less-than-or-equal-to 0% was achieved (6% versus 33%, p=0.02). When multiple overlapping stents were placed, restenosis occurred at 64% of sites, and placement of multiple stents was discouraged during the later phases of this study as these results became apparent. Conclusions. Although multiple stents appear to yield a poor long-term result, placement of single stents may offer a benefit compared with standard coronary angioplasty, particularly if an excellent angiographic result can be obtained in patients without prior restenosis. Further randomized trials in such patients are needed. C1 UNIV MICHIGAN, MED CTR, ANN ARBOR, MI 48109 USA. THOMAS JEFFERSON UNIV, PHILADELPHIA, PA 19107 USA. BETH ISRAEL HOSP, BOSTON, MA 02215 USA. NIH, BETHESDA, MD 20892 USA. WASHINGTON HOSP CTR, WASHINGTON, DC 20010 USA. HOSP UNIV PENN, PHILADELPHIA, PA 19104 USA. YALE NEW HAVEN MED CTR, NEW HAVEN, CT 06504 USA. SCRIPPS MED CLIN, LA JOLLA, CA USA. CARDIOVASC INST S, HOUMA, LA USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. NR 68 TC 224 Z9 226 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC PY 1992 VL 86 IS 6 BP 1836 EP 1844 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KB491 UT WOS:A1992KB49100018 PM 1451256 ER PT J AU QUYYUMI, AA CANNON, RO PANZA, JA DIODATI, JG EPSTEIN, SE AF QUYYUMI, AA CANNON, RO PANZA, JA DIODATI, JG EPSTEIN, SE TI ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH CHEST PAIN AND NORMAL CORONARY-ARTERIES SO CIRCULATION LA English DT Article DE ENDOTHELIUM-DERIVED RELAXING FACTOR; ANGINA; MICROCIRCULATION; VASODILATION ID RELAXING FACTOR; SMOOTH-MUSCLE; NITRIC-OXIDE; BLOOD-FLOW; ESSENTIAL-HYPERTENSION; DEPENDENT RELAXATION; RESISTANCE VESSELS; MEDIATED DILATION; ANGINA-PECTORIS; ACETYLCHOLINE AB Background. A subgroup of patients with chest pain and angiographically normal epicardial coronary arteries have reduced dilator response to metabolic or pharmacological stimuli but the mechanisms responsible for this reduced dilator response are unknown. In this study, we have investigated whether microvascular endothelial dysfunction is a cause of the observed reduced vasodilator reserve. Methods and Results. The functional response of the microvasculature was studied with rapid atrial pacing at 150 beats per minute. Fifty-one patients, 20 hypertensive and 31 normotensive, with chest pain and normal epicardial coronary arteries (<10% stenosis) were studied. Endothelial function was tested with incremental infusions of acetylcholine to achieve estimated intracoronary concentrations ranging from 10(-7) M to 10(-5) M. Endothelium-independent smooth muscle vasomotion was measured using intracoronary sodium nitroprusside. Endothelial dysfunction of epicardial coronary arteries, demonstrated as severe (>50%) constriction with <10(-5) M acetylcholine concentration, was evident in five patients (10%). In the remaining 46 patients, coronary blood flow increased with acetylcholine (mean, 78 +/- 43%) and atrial pacing (mean, 51 +/- 37%), and coronary vascular resistance decreased by 35 +/- 16% and 29 +/- 14%, respectively, but the responses were heterogeneous. There was a correlation between the coronary resistance change with acetylcholine and the change with atrial pacing: r=0.68, p<0.001 in these 46 patients. Thus, patients with depressed dilation with atrial pacing had reduced endothelium-dependent dilation with acetylcholine, and vice versa. However, the microvascular dilation caused by sodium nitroprusside was not significantly different between patients with and those without reduced dilation with atrial pacing, indicating that the vasodilator defect was not caused by smooth muscle dysfunction. There were no differences in the vasodilator responses with atrial pacing, acetylcholine, or nitroprusside between normotensive and hypertensive patients. Multivariate regression analysis was performed to determine whether age, sex, serum cholesterol level, hypertension, presence of mild epicardial vessel atherosclerosis, resting left ventricular function, change in left ventricular ejection fraction with exercise, vasodilation with acetylcholine, and vasodilation with sodium nitroprusside were independently related to the vasodilator response to atrial pacing. Only the change in coronary vascular resistance with acetylcholine was independently correlated with the change in resistance with atrial pacing: R2=0.46, p<0.0001. Conclusions. Patients with chest pain, normal epicardial coronary arteries, and reduced vasodilation in response to atrial pacing appear to have associated endothelial dysfunction of the coronary microvasculature. Thus, microvascular endothelial dysfunction may contribute to the reduced vasodilator reserve with atrial pacing and anginal chest pain in these patients. RP QUYYUMI, AA (reprint author), NHLBI,DIV CARDIOL,BLDG 10,ROOM 7B 15,BETHESDA,MD 20892, USA. NR 45 TC 185 Z9 188 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1992 VL 86 IS 6 BP 1864 EP 1871 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KB491 UT WOS:A1992KB49100021 PM 1451258 ER PT J AU KAHN, ML LEE, SW DICHEK, DA AF KAHN, ML LEE, SW DICHEK, DA TI OPTIMIZATION OF RETROVIRAL VECTOR-MEDIATED GENE-TRANSFER INTO ENDOTHELIAL-CELLS INVITRO SO CIRCULATION RESEARCH LA English DT Article DE GENE TRANSFER; ENDOTHELIAL CELL; RETROVIRUS; DEAE-DEXTRAN ID HEMATOPOIETIC STEM-CELLS; LYMPHOCYTES-T; EXPRESSION; CULTURE; TRANSPLANTATION; IDENTIFICATION; IMPLANTATION; INFECTION; PROMOTER; THERAPY AB Retroviral vector-mediated gene transfer into endothelial cells is relatively inefficient with transduction rates as low as 1-2% in vitro and even lower in vivo. To increase the efficiency of gene transfer into endothelial cells, we used retroviral vectors expressing beta-galactosidase and urokinase and measured endothelial cell transduction efficiencies with quantitative assays for beta-galactosidase and urokinase protein. We evaluated several techniques reported to improve the efficiency of retroviral transduction in vitro, including 1) extended periods of exposure to vector, 2) repeated exposures to vector, 3) maximization of the ratio of vector particles to endothelial cells by increasing the volume and concentration of vector particles or by decreasing the number of endothelial cells exposed, 4) cocultivation of endothelial cells with vector-producing cells, and 5) variation of the type and concentration of polycation used with the retroviral vector. Only the use of more concentrated (higher titer) vector-containing supernatant and the use of the polycation DEAE-dextran improved the efficiency of gene transfer into endothelial cells in vitro. In an optimized transduction protocol, a 60-second exposure to 1 mg/ml DEAE-dextran followed by a single 6-hour exposure to supernatant of a titer of 10(5)-10(6) colony-forming units/ml resulted in transduction efficiencies of 50-90% with both vectors. Decreasing the time of the supernatant exposure to 15 minutes permitted transduction efficiencies of 15-20% while significantly minimizing the duration of the transduction. Therefore, the optimized protocol allows high efficiency in vitro gene transfer into endothelial cells within several hours. The briefer protocol may prove useful for in vivo gene transfer in which the time of exposure to the supernatant is limited. C1 NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,ROOM 7D-18,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 52 TC 41 Z9 41 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 1992 VL 71 IS 6 BP 1508 EP 1517 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA JZ072 UT WOS:A1992JZ07200024 PM 1423943 ER PT J AU LI, Q FUJINO, Y CASPI, RR NAJAFIAN, F NUSSENBLATT, RB CHAN, CC AF LI, Q FUJINO, Y CASPI, RR NAJAFIAN, F NUSSENBLATT, RB CHAN, CC TI ASSOCIATION BETWEEN MAST-CELLS AND THE DEVELOPMENT OF EXPERIMENTAL AUTOIMMUNE UVEITIS IN DIFFERENT RAT STRAINS SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; DE-GRANULATION; LEWIS RATS; S-ANTIGEN; UVEORETINITIS; EXPRESSION; BASOPHILS; ADHESION; PRODUCE; ICAM-1 RP LI, Q (reprint author), NEI,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 29 TC 16 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD DEC PY 1992 VL 65 IS 3 BP 294 EP 299 DI 10.1016/0090-1229(92)90160-P PG 6 WC Immunology; Pathology SC Immunology; Pathology GA KB992 UT WOS:A1992KB99200015 PM 1451332 ER PT J AU MELBY, PC KREUTZER, RD MCMAHONPRATT, D GAM, AA NEVA, FA AF MELBY, PC KREUTZER, RD MCMAHONPRATT, D GAM, AA NEVA, FA TI CUTANEOUS LEISHMANIASIS - REVIEW OF 59 CASES SEEN AT THE NATIONAL-INSTITUTES-OF-HEALTH SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SODIUM STIBOGLUCONATE; MUCOCUTANEOUS LEISHMANIASIS; MUCOSAL LEISHMANIASIS; BRAZILIENSIS-GUYANENSIS; PENTAVALENT ANTIMONY; SAUDI-ARABIA; KETOCONAZOLE; EFFICACY; IDENTIFICATION; EPIDEMIOLOGY AB Fifty-nine cases of cutaneous leishmaniasis seen at the National Institutes of Health in Bethesda, Maryland, are reviewed. The group of patients involved was unique in that the majority were American civilians, their disease was acquired in many different endemic areas of the world, and their illnesses represented all points on the clinical spectrum of cutaneous disease. The majority of American patients acquired leishmaniasis while engaging in activities related to their occupations. Cutaneous disease acquired in the New World usually consisted of one or two lesions, while multiple lesions often characterized Old World infections with Leishmania major. Patients with chronic relapsing or diffuse cutaneous leishmaniasis were native to endemic areas and were infected at an early age. Even the localized form of cutaneous leishmaniasis was often extensive and difficult to treat. Diagnosis with culture and identification of the parasite to the subspecies level is instrumental in the selection of optimal therapy. Cutaneous leishmaniasis may be encountered increasingly often in the United States because of the frequent international travel of U.S. residents and the influx of immigrants from endemic areas of the world. C1 YOUNGSTOWN STATE UNIV, DEPT BIOL, YOUNGSTOWN, OH 44555 USA. NIAID, PARASIT DIS LAB, BETHESDA, MD 20892 USA. YALE UNIV, SCH MED, DEPT EPIDEMIOL & PUBL HLTH, NEW HAVEN, CT 06510 USA. NR 103 TC 68 Z9 69 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC PY 1992 VL 15 IS 6 BP 924 EP 937 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JZ600 UT WOS:A1992JZ60000004 PM 1457663 ER PT J AU FRANCIS, P WALSH, TJ AF FRANCIS, P WALSH, TJ TI EVOLVING ROLE OF FLUCYTOSINE IN IMMUNOCOMPROMISED PATIENTS - NEW INSIGHTS INTO SAFETY, PHARMACOKINETICS, AND ANTIFUNGAL THERAPY SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; ACQUIRED IMMUNODEFICIENCY SYNDROME; GAS-CHROMATOGRAPHIC DETERMINATION; CENTRAL NERVOUS-SYSTEM; ACUTE MYELOID-LEUKEMIA; B PLUS FLUCYTOSINE; AMPHOTERICIN-B; CRYPTOCOCCAL MENINGITIS; HEPATIC CANDIDIASIS; FUNGAL-INFECTIONS AB Flucytosine is an antifungal agent useful in combination with amphotericin B in the treatment of several deeply invasive mycoses. The potentially dose-limiting, hematologic, gastrointestinal, and hepatic toxicities of flucytosine lead to a reluctance to use it in myelosuppressed patients. To investigate the safety and tolerability of flucytosine in this setting, we evaluated its use in 17 patients with cancer or aplastic anemia during a 2 1/2-year period at our institution and reviewed the literature describing mechanisms of action, resistance, in vitro and in vivo antifungal activity, clinical antifungal activity, pharmacokinetics, and toxicity. The combination of amphotericin B plus flucytosine eradicated the mycosis in 12 (71%) of 17 patients, whereas 3 (18%) of 17 died of progressive fungal infection. Serial serum levels of flucytosine measured by a creatinine iminohydrolase assay permitted reliable dosage adjustment. During therapy, only 2 (12%) of 17 patients had elevated mean serum levels of flucytosine (>100 mug/mL) and 3 (18%) other patients had transiently elevated levels. Paired serum samples (n = 45) obtained at steady state during therapy with orally administered flucytosine showed similar peak and trough levels. Adverse effects of flucytosine therapy included one case each of reversible nausea, diarrhea, elevated transaminase levels, and thrombocytopenia. No cases of bone marrow aplasia, enterocolitis, hepatitis, or death due to flucytosine toxicity were encountered. We conclude that flucytosine in combination with amphotericin B is well tolerated in myelosuppressed patients when serum flucytosine levels are serially monitored. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,ROOM 13N240,BALTIMORE,MD 21211. NR 117 TC 143 Z9 146 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC PY 1992 VL 15 IS 6 BP 1003 EP 1018 PG 16 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JZ600 UT WOS:A1992JZ60000014 PM 1457631 ER PT J AU COOPER, DR CHALFANT, C WATSON, J STANDAERT, ML FARESE, RV MISCHAK, H AF COOPER, DR CHALFANT, C WATSON, J STANDAERT, ML FARESE, RV MISCHAK, H TI EXPRESSION OF PROTEIN-KINASE C-BETA-I AND C-BETA-II IN INSULIN-SENSITIVE BC3H-1 MYOCYTES SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 JAMES A HALEY VET ADM MED CTR,TAMPA,FL 33612. UNIV S FLORIDA,TAMPA,FL 33620. NCI,BETHESDA,MD 20892. RI Mischak, Harald/E-8685-2011; Farese, Robert/B-3605-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD DEC PY 1992 VL 40 IS 4 BP A814 EP A814 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE141 UT WOS:A1992KE14100233 ER PT J AU HOFFMAN, HJ HILLMAN, LS AF HOFFMAN, HJ HILLMAN, LS TI EPIDEMIOLOGY OF THE SUDDEN-INFANT-DEATH-SYNDROME - MATERNAL, NEONATAL, AND POSTNEONATAL RISK-FACTORS SO CLINICS IN PERINATOLOGY LA English DT Review ID HEART-RATE-VARIABILITY; LOW-BIRTH-WEIGHT; COT DEATH; UNEXPECTED DEATH; SLEEPING POSITION; SYNDROME SIDS; POSSIBLE MECHANISMS; GROWTH-RETARDATION; RECORD LINKAGE; UNITED-STATES C1 NIDOCD,EPIDEMIOL STAT & DATA SYST BRANCH,BETHESDA,MD. UNIV MISSOURI,HLTH SCI CTR,DEPT CHILD HLTH,COLUMBIA,MO 65201. NR 148 TC 147 Z9 149 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD DEC PY 1992 VL 19 IS 4 BP 717 EP 737 PG 21 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA LA272 UT WOS:A1992LA27200003 PM 1464187 ER PT J AU BRANT, LJ PEARSON, JD MORRELL, CH VERBEKE, GNM AF BRANT, LJ PEARSON, JD MORRELL, CH VERBEKE, GNM TI STATISTICAL-METHODS FOR STUDYING INDIVIDUAL CHANGE DURING AGING SO COLLEGIUM ANTROPOLOGICUM LA English DT Article ID LONGITUDINAL DATA; EFFECTS MODELS AB Using mixed-effects regression models, it is now possible to study individual patterns of change and to identify factors which may affect that pattern of change. Data collected for such studies are longitudinal repeated measurements, which may be characterized by unequally spaced points of observation (unbalanced in time), missing data, attrition, time-varying covariates, and the correlation between repeated observations for an individual. Recent developments in estimation procedures and numerical techniques (e.g., restricted maximum likelihood and Newton- Raphson method) have made it possible to estimate the average rates of change, as well as individual deviations from the average rates of change. Some special uses of mixed-effects models would be to identify outlying individuals, and to examine cross-sectional and longitudinal age differences within the framework of the same analysis. RP BRANT, LJ (reprint author), NIA,GERONTOL RES CTR,BALTIMORE,MD 21224, USA. RI Verbeke, Geert/I-5587-2015 NR 11 TC 5 Z9 5 U1 0 U2 3 PU SCH BIOLOGICAL ANTHROPOLOGY PI ZAGREB PA MOSE PIJADE 158 P O BOX 291, 41001 ZAGREB, CROATIA SN 0350-6134 J9 COLLEGIUM ANTROPOL JI Coll. Anthropol. PD DEC PY 1992 VL 16 IS 2 BP 359 EP 369 PG 11 WC Anthropology SC Anthropology GA KG557 UT WOS:A1992KG55700018 ER PT J AU BOUFFARD, G OSTELL, J RUDD, KE AF BOUFFARD, G OSTELL, J RUDD, KE TI GENESCAPE - A RELATIONAL DATABASE OF ESCHERICHIA-COLI GENOMIC MAP DATA FOR MACINTOSH COMPUTERS SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID SEARCHING RESTRICTION MAPS AB We present a relational database program developed in FoxBase+/Mac for the viewing and manipulation of ordered restriction maps and associated features of the Escherichia coli genome including sequenced genes and the Kohara miniset of bacteriophage lambda clones. Use of this program allows easy access to the wealth of information being collected in a dataset of DNA sequences, maps and genetic data known as EcoSeq, EcoMap and EcoGene respectively. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. GEORGE WASHINGTON UNIV,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20037. RP RUDD, KE (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 7 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD DEC PY 1992 VL 8 IS 6 BP 563 EP 567 PG 5 WC Computer Science, Interdisciplinary Applications SC Computer Science GA KD321 UT WOS:A1992KD32100006 PM 1468012 ER PT J AU SHEA, S BIGGER, JT CAMPION, J FLEISS, JL ROLNITZKY, LM SCHRON, E GORKIN, L HANDSHAW, K KINNEY, MR BRANYON, M AF SHEA, S BIGGER, JT CAMPION, J FLEISS, JL ROLNITZKY, LM SCHRON, E GORKIN, L HANDSHAW, K KINNEY, MR BRANYON, M TI ENROLLMENT IN CLINICAL-TRIALS - INSTITUTIONAL FACTORS AFFECTING ENROLLMENT IN THE CARDIAC-ARRHYTHMIA SUPPRESSION TRIAL (CAST) SO CONTROLLED CLINICAL TRIALS LA English DT Article DE CLINICAL TRIAL; ENROLLMENT ID ONCOLOGY-GROUP; PARTICIPATION; QUALITY AB Recruitment and Enrollment Assessment in Clinical Trials (REACT), an NHLBI-sponsored substudy of the Cardiac Arrhythmia Suppression Trial (CAST), was conducted to assess factors associated with enrollment in clinical trials. We report on the relationships of institutional factors at CAST sites to patient enrollment. The proportion of CAST-eligible patients enrolling at each CAST site during the REACT study period was defined as the number of subjects enrolled divided by the sum of (1) the number enrolled plus (2) the number of eligibles who refused plus (3) the number of eligibles whose physicians refused to permit CAST personnel to attempt to enroll them. A questionnaire that included 78 questions regarding factors hypothesized to be associated with enrollment was completed between August 1988 and February 1990 by the nurse coordinators at all 112 CAST sites in the United States and Canada. Sixteen items were unanalyzable, and 37 of the remaining 62 were grouped into seven scales. The remaining items were analyzed individually. Enrollment proportions varied widely across the 112 CAST sites (mean 32.7% SD 22.6). Five variables or scales were included in the final multiple regression model (multiple R2 = .39). The most important of these was the proportion of eligible patients at a site cared for by medical staff other than private attending physicians (multiple R2 for this variable alone, .26). This proportion tended to be high in teaching hospitals. Other variables in this model that were associated with higher enrollment proportions included the number of days per week a nurse coordinator was present at the site, the number of nurse coordinator full-time equivalents at the site, fewer other clinical trials for which the nurse coordinator was responsible, and fewer perceived obstacles to enrollment. These findings indicate that enrollment was more successful at hospitals with higher proportions of eligible subjects cared for by fellows, housestaff, and service attending physicians and at institutions with the committed presence of a nurse-coordinator. C1 COLUMBIA UNIV COLL PHYS & SURG, DEPT MED, DIV GEN MED, NEW YORK, NY 10032 USA. COLUMBIA UNIV, SCH PUBL HLTH, DIV EPIDEMIOL, NEW YORK, NY 10027 USA. COLUMBIA UNIV COLL PHYS & SURG, DEPT MED, DIV CARDIOL, NEW YORK, NY 10032 USA. PRESBYTERIAN HOSP, NEW YORK, NY 10032 USA. COLUMBIA UNIV, SCH PUBL HLTH, DIV BIOSTAT, NEW YORK, NY 10027 USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, WASHINGTON, DC USA. INST BEHAV MED INC, PROVIDENCE, RI USA. RHODE ISL HOSP, PROVIDENCE, RI 02902 USA. UNIV ALABAMA, SCH NURSING, BIRMINGHAM, AL 35294 USA. FU NHLBI NIH HHS [HL40093, HL40140, HL40166] NR 19 TC 21 Z9 21 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 EI 1879-050X J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1992 VL 13 IS 6 BP 466 EP 486 DI 10.1016/0197-2456(92)90204-D PG 21 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA KD988 UT WOS:A1992KD98800004 PM 1334819 ER PT J AU GAUDET, SJ CHADER, GJ AF GAUDET, SJ CHADER, GJ TI PARTIAL-PURIFICATION AND CHARACTERIZATION OF ARYLAMINE N-ACETYLTRANSFERASE IN BOVINE RETINA SO CURRENT EYE RESEARCH LA English DT Article ID PINEAL-GLAND; HUMAN-LIVER; ACETYL-COA; MELATONIN; EYE AB Arylamine N-acetyltransferase (NAT) activity was partially purified and characterized in bovine retina. Upon examining the retinal supernatant for multiple ionic species, only one NAT activity was detected. Based upon its substrate specificity, it is best described as an arylamine NAT. According to size-exclusion HPLC, the molecular mass of the arylamine NAT is approximately 30-kDa. This arylamine NAT acetylates p-aminobenzoic acid thereby demonstrating a monomorphic pattern of acetylation. The NAT activity demonstrated low sensitivity to methotrexate inhibition as indicated by a high IC50 value (480 muM). RP GAUDET, SJ (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,RM 309,BETHESDA,MD 20892, USA. NR 19 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD DEC PY 1992 VL 11 IS 12 BP 1185 EP 1192 DI 10.3109/02713689208999543 PG 8 WC Ophthalmology SC Ophthalmology GA KH955 UT WOS:A1992KH95500007 PM 1490336 ER PT J AU RUSSELL, P EPSTEIN, DL AF RUSSELL, P EPSTEIN, DL TI PROTEIN-ANALYSIS OF MONKEY AQUEOUS-HUMOR SO CURRENT EYE RESEARCH LA English DT Note AB Aqueous humor from individual eyes of young monkeys (Macaca mulatta) was analyzed by gel exclusion chromatography, and one- and two-dimensional gel electrophoresis. The data indicated that in young normal monkey the main peak of protein eluting from gel exclusion columns was observed around 80,000 daltons. There was a small amount of heavy molecular weight material eluting from these columns with an apparent molecular size of greater than 500,000 daltons, but very little material smaller than 40,000 daltons. By one- and two-dimensional gel electrophoresis, the major polypeptide components in the monkey aqueous were similar to those reported for the human aqueous with polypeptides at around 170, 130, 110, 80, 67, 60, 42, 34, 28, 25, 22, 16, and 14 kilodaltons (kD). The monkey aqueous humor also contains the protease inhibitor cystatin. C1 NEI,BETHESDA,MD 20892. DUKE UNIV,DEPT OPHTHALMOL,DURHAM,NC 27706. FU PHS HHS [R01-01894] NR 12 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD DEC PY 1992 VL 11 IS 12 BP 1239 EP 1243 DI 10.3109/02713689208999550 PG 5 WC Ophthalmology SC Ophthalmology GA KH955 UT WOS:A1992KH95500014 PM 1490343 ER PT J AU ZIMMER, A ZIMMER, A AF ZIMMER, A ZIMMER, A TI INDUCTION OF A RAR-BETA-2-LACZ TRANSGENE BY RETINOIC ACID REFLECTS THE NEUROMERIC ORGANIZATION OF THE CENTRAL-NERVOUS-SYSTEM SO DEVELOPMENT LA English DT Article DE TRANSGENIC MICE; SEGMENTATION; RETINOIC ACID; LACZ; GENE EXPRESSION ID SEGMENT-SPECIFIC EXPRESSION; RECEPTOR-GAMMA; RESPONSE ELEMENT; CHICK HINDBRAIN; MOUSE EMBRYOS; GENE; IDENTIFICATION; MORPHOGENESIS; BETA; FOREBRAIN AB The hormone retinoic acid (RA) has been implicated in the organization of the anteroposterior (AP) body axis. In this paper, we describe the effects of RA on the activity of the RA-inducible retinoic acid receptor-beta2 (RARbeta2) promoter. When transgenic embryos carrying a RARbeta2-lacZ reporter gene were exposed to a single dose of RA between gestational days 8.5 to 10.5, lacZ expression was induced in the anterior central nervous system (CNS). Strikingly, the transgene was expressed in a segmented pattern reminiscent of that of Drosophila 'pair-rule' genes. RA treatment of midgastrulation embryos at day 7.5 disturbed the segmentation and produced severe craniofacial defects. We discuss the possibility that the entire anterior CNS is segmented and that this segmentation is reflected by the RARbeta2-lacZ induction pattern. RP ZIMMER, A (reprint author), NIMH,CELL BIOL LAB,DEV BIOL UNIT,BETHESDA,MD 20892, USA. RI Zimmer, Andreas/B-8357-2009 NR 58 TC 40 Z9 40 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 1992 VL 116 IS 4 BP 977 EP & PG 0 WC Developmental Biology SC Developmental Biology GA KG067 UT WOS:A1992KG06700013 PM 1338313 ER PT J AU JAKOWLEW, SB CIMENT, G TUAN, RS SPORN, MB ROBERTS, AB AF JAKOWLEW, SB CIMENT, G TUAN, RS SPORN, MB ROBERTS, AB TI PATTERN OF EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-4 MESSENGER-RNA AND PROTEIN IN THE DEVELOPING CHICKEN-EMBRYO SO DEVELOPMENTAL DYNAMICS LA English DT Article DE TGF-BETA-4; EXPRESSION; DEVELOPMENT; CHICKEN ID FACTOR-TYPE-BETA; DEOXYRIBONUCLEIC-ACID CLONING; CELL-ADHESION; RIBONUCLEIC-ACID; ADULT TISSUES; MOUSE EMBRYO; TGF BETA-1; COLLAGEN; TGF-BETA-1; PURIFICATION AB Expression of TGF-beta4 mRNA and protein was studied in the developing chicken embryo using specific cDNA probes and antibodies for chicken TGF-beta4. Expression of TGF-beta4 mRNA was detected by day 4 of incubation (Hamburger and Hamilton stage 22, E4) by RNA Northern blot analysis and increased with developmental age until day 12 of incubation (stage 38, E12) where it was detected in every embryonic tissue examined, with expression being highest in smooth muscle and lowest in the kidney. The steady-state level of expression of TGF-beta4 mRNA remained relatively constant in most embryonic tissues through day 19 (stage 45, E19). In situ hybridization analysis detected TGF-beta4 mRNA as early as the ''definitive primitive streak'' stage (stage 4); during neurulation (stage 10), TGF-beta4 mRNA was detected in all three germ layers, including neuroectoderm. Following neurulation, TGF-beta4 mRNA was detected in the neural tube, notochord, ectoderm, endoderm, sclerotome, and myotome, but not dermotome at stage 16. By day 6 of incubation (stage 29, E6), TGF-beta4 mRNA was localized in several tissues including heart, lung, and gizzard. Immunohistochemical staining analysis also showed expression of TGF-beta4 protein in all three germ layers as early as stage 4 in various cell types in qualitatively similar locations as TGF-beta4 MRNA. These results suggest that TGF-beta4 may play an important role in the development of many tissues in the chicken. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,DEPT CELL BIOL & ANAT,PORTLAND,OR 97201. THOMAS JEFFERSON UNIV,DEPT ORTHOPAED SURG,PHILADELPHIA,PA 19107. FU NICHD NIH HHS [HD 15822]; NINDS NIH HHS [NS 23883] NR 54 TC 29 Z9 29 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 1992 VL 195 IS 4 BP 276 EP 289 DI 10.1002/dvdy.1001950406 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA LA040 UT WOS:A1992LA04000004 PM 1304823 ER PT J AU VALLSSOLE, J PASCUALLEONE, A WASSERMANN, EM HALLETT, M AF VALLSSOLE, J PASCUALLEONE, A WASSERMANN, EM HALLETT, M TI HUMAN MOTOR EVOKED-RESPONSES TO PAIRED TRANSCRANIAL MAGNETIC STIMULI SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE MOTOR CORTEX; SPINAL MOTONEURON; MAGNETIC STIMULATION; PAIRED STIMULATION; EXCITABILITY; INTRACORTICAL INHIBITION ID INTACT MAN; CORTEX STIMULATION; HUMAN-BRAIN; POTENTIALS; MUSCLES AB We studied the changes in motor pathway excitability induced by transcranial magnetic stimulation of the motor cortex, using paired stimuli (conditioning and test stimulus) and a varying interstimulus interval (ISI). The effects induced depended on the stimulus intensity. At a low intensity, there was inhibition of the response to the test stimulus at ISIs of 5-40 msec, followed by facilitation at ISIs of 50-90 msec. At a high intensity, there was facilitation at ISIs of 25-50 msec, followed by inhibition at ISIs of 60-150 msec and, occasionally, by another phase of facilitation at ISIs of more than 200 msec. Only tentative explanations are currently possible for these effects: the inhibition observed at low intensities and short ISIs may be due to activation of cortical inhibitory mechanisms. The facilitation that follows may arise from the coincidence of various factors that transiently increase the excitability in alpha motoneurons. The early facilitation observed at high intensities seems to be a consequence of a rise in cortical excitability induced by the conditioning stimulus, causing an increase in the number or size, or both, of descending volleys from the test stimulus. The profound inhibition that follows probably results from a combination of both segmental and suprasegmental inhibitory mechanisms. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BLDG 10,BETHESDA,MD 20892. RI Pascual-Leone, Alvaro/G-6566-2011 NR 32 TC 366 Z9 369 U1 1 U2 11 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD DEC PY 1992 VL 85 IS 6 BP 355 EP 364 DI 10.1016/0168-5597(92)90048-G PG 10 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA KG038 UT WOS:A1992KG03800001 PM 1282453 ER PT J AU BIESSMANN, H CHAMPION, LE OHAIR, M IKENAGA, K KASRAVI, B MASON, JM AF BIESSMANN, H CHAMPION, LE OHAIR, M IKENAGA, K KASRAVI, B MASON, JM TI FREQUENT TRANSPOSITIONS OF DROSOPHILA-MELANOGASTER HET-A TRANSPOSABLE ELEMENTS TO RECEDING CHROMOSOME ENDS SO EMBO JOURNAL LA English DT Article DE CHROMOSOME HEALING; DROSOPHILA; RECEDING CHROMOSOME ENDS; TELOMERE; TRANSPOSON ID R HYBRID DYSGENESIS; DNA-SEQUENCES; MOLECULAR ANALYSIS; MAMMALIAN LINES; TELOMERE; RETROPOSONS; GENE; RETROTRANSPOSONS; HETEROCHROMATIN; TETRAHYMENA AB HeT-A elements are a new family of transposable elements in Drosophila that are found exclusively in telomeric regions and in the pericentric heterochromatin. Transposition of these elements onto broken chromosome ends has been implicated in chromosome healing. To monitor the fate of HeT-A elements that had attached to broken ends of the X chromosome, we examined individual X chromosomes from a defined population over a period of 17 generations. The ends of the X chromosomes with new HeT-A additions receded at the same rate as the broken ends before the HeT-A elements attached. In addition, some chromosomes, approximately 1% per generation, had acquired new HeT-A sequences of an average of 6 kb at their ends with oligo(A) tails at the junctions. Thus, the rate of addition of new material per generation matches the observed rate of terminal loss (70-75 bp) caused by incomplete replication at the end of the DNA molecule. One such recently transposed HeT-A element which is at least 12 kb in length has been examined in detail. It contains a single open reading frame of 2.8 kb which codes for a gag-like protein. C1 NIEHS,CELLULAR & GENET TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. RP BIESSMANN, H (reprint author), UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92717, USA. NR 50 TC 120 Z9 121 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC PY 1992 VL 11 IS 12 BP 4459 EP 4469 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JY101 UT WOS:A1992JY10100023 PM 1330538 ER PT J AU ANDERSON, SJ ABRAHAM, KM NAKAYAMA, T SINGER, A PERLMUTTER, RM AF ANDERSON, SJ ABRAHAM, KM NAKAYAMA, T SINGER, A PERLMUTTER, RM TI INHIBITION OF T-CELL RECEPTOR BETA-CHAIN GENE REARRANGEMENT BY OVEREXPRESSION OF THE NONRECEPTOR PROTEIN TYROSINE KINASE-P56LCK SO EMBO JOURNAL LA English DT Article DE GERMLINE TRANSCRIPTION; LCK TRANSGENIC MICE; V-BETA REARRANGEMENT ID ANTIGEN RECEPTOR; TRANSGENIC MICE; V(D)J RECOMBINATION; DEVELOPMENTAL REGULATION; THYMOCYTE DEVELOPMENT; KINASE P56LCK; LYMPHOCYTES-T; EXPRESSION; CD4; TRANSCRIPTION AB The variable region genes of the T cell receptor (TCR) alpha and beta chains are assembled by somatic recombination of separate germline elements. During thymocyte development, gene rearrangements display both an ordered progression, with beta chain formation preceding alpha chain, and allelic exclusion, with each cell containing a single functional beta chain rearrangement. Although considerable evidence supports the view that the individual loci are regulated independently, signaling molecules that may participate in controlling TCR gene recombination remain unidentified. Here we report that the lymphocyte-specific protein tyrosine kinase p56lck, when overexpressed in developing thymocytes, provokes a reduction in Vbeta-Dbeta rearrangement while permitting normal juxtaposition of other TCR gene segments. Our data support a model in which p56lck activity impinges upon a signaling process that ordinarily permits allelic exclusion at the beta-chain locus. C1 UNIV WASHINGTON,DEPT IMMUNOL,SEATTLE,WA 98195. UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOCHEM & MED,SEATTLE,WA 98195. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP PERLMUTTER, RM (reprint author), UNIV WASHINGTON,DEPT IMMUNOL,SEATTLE,WA 98195, USA. RI Nakayama, Toshinori/E-1067-2017 FU NCI NIH HHS [CA45682] NR 56 TC 184 Z9 185 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC PY 1992 VL 11 IS 13 BP 4877 EP 4886 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KC837 UT WOS:A1992KC83700023 PM 1334460 ER PT J AU WANG, LM KEEGAN, AD PAUL, WE HEIDARAN, MA GUTKIND, JS PIERCE, JH AF WANG, LM KEEGAN, AD PAUL, WE HEIDARAN, MA GUTKIND, JS PIERCE, JH TI IL-4 ACTIVATES A DISTINCT SIGNAL TRANSDUCTION CASCADE FROM IL-3 IN FACTOR-DEPENDENT MYELOID CELLS SO EMBO JOURNAL LA English DT Article DE INTERLEUKIN-3; INTERLEUKIN-4; PHOSPHATIDYLINOSITOL-3-KINASE; SIGNAL TRANSDUCTION; TYROSINE PHOSPHORYLATION ID STIMULATORY FACTOR-I; HUMAN INTERLEUKIN-4 RECEPTOR; PDGF BETA-RECEPTOR; MOUSE B-CELLS; TYROSINE PHOSPHORYLATION; T-CELL; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL-3 KINASE; RAPID PHOSPHORYLATION; EXPRESSION CLONING AB Interleukin-4 (IL4) was shown to induce a potent mitogenic response in the IL-3-dependent myeloid progenitor cell line, FDCP-2. Although IL4 could not sustain long-term growth of FDCP-2 cells, it enhanced their growth in serum-free medium containing IL-3. IL-4 triggered prominent tyrosine phosphorylation of a substrate(s) migrating at 170 kDa and less striking phosphorylation of several other proteins, including the IL-4 receptor. By contrast, IL-3 induced distinct tyrosine phosphorylation of proteins migrating at 145, 97, 70, 55 and 52 kDa in the same cell line. IL-4 treatment of FDCP-2 cells caused a dramatically strong association of phosphatidylinositol 3-kinase (PI 3-kinase) both with the 170 kDa tyrosine phosphorylated substrate and with the IL-4 receptor itself. By contrast, IL-3 triggered only weak association of PI 3-kinase activity with the 97 kDa substrate. While IL-4 did not affect cellular raf, IL-3 stimulation did induce a shift in its mobility presumably due to serine/threonine phosphorylation. Taken together, our results indicate that IL-4 and IL-3 activate distinct phosphorylation cascades in the same cell background; this may reflect a difference in the biological function of these two cytokines. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. NAIAD,IMMUNOL LAB,BETHESDA,MD. RP WANG, LM (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Gutkind, J. Silvio/A-1053-2009 NR 65 TC 190 Z9 190 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC PY 1992 VL 11 IS 13 BP 4899 EP 4908 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KC837 UT WOS:A1992KC83700025 PM 1334461 ER PT J AU MIETZ, JA UNGER, T HUIBREGTSE, JM HOWLEY, PM AF MIETZ, JA UNGER, T HUIBREGTSE, JM HOWLEY, PM TI THE TRANSCRIPTIONAL TRANSACTIVATION FUNCTION OF WILD-TYPE-P53 IS INHIBITED BY SV40 LARGE T-ANTIGEN AND BY HPV-16 E6-ONCOPROTEIN SO EMBO JOURNAL LA English DT Article DE HPV-E6; HUMAN PAPILLOMAVIRUS; P53; SV40 LARGE T-ANTIGEN; TRANSCRIPTIONAL ACTIVATION ID HUMAN PAPILLOMAVIRUS TYPE-16; LARGE TUMOR-ANTIGEN; RETINOBLASTOMA GENE-PRODUCT; WILD-TYPE P53; MUTANT P53; TRANSFORMED-CELLS; PROTEINS BIND; BREAST-CANCER; MUTATIONS; ONCOGENE AB The observed interaction between p53 and the oncoproteins encoded by several DNA tumor viruses suggests that these viruses mediate their transforming activities at least in part by altering the normal growth regulatory function of p53. In this study we examined the effect of viral oncoprotein expression on the transcriptional transactivation function of wild-type p53 in human cells. Plasmids expressing human p53 were cotransfected with either SV40 large T-antigen or human papillomavirus (HPV) type 16 E6 expression plasmids and assayed for transactivation function using a reporter gene driven by a p53-responsive promoter containing multiple copies of the consensus p53 DNA binding motif, TGCCT. Both large T-antigen and E6 were able to inhibit transactivation by wild-type p53. Furthermore, SV40 T-antigen mutants that are defective for p53 binding were not able to inhibit transactivation and HPV E6 proteins that were either mutant or derived from non-oncogenic HPV types and unable to bind p53, had no effect on p53 transactivation. These results demonstrate the physiological relevance of the interaction of SV40 T-antigen and HPV E6 oncoproteins with p53 in vivo and suggest that the transforming functions of these viral oncoproteins may be linked to their ability to inhibit p53-mediated transcriptional activation. RP MIETZ, JA (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. NR 52 TC 349 Z9 351 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC PY 1992 VL 11 IS 13 BP 5013 EP 5020 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KC837 UT WOS:A1992KC83700037 PM 1464323 ER PT J AU KOTIN, RM LINDEN, RM BERNS, KI AF KOTIN, RM LINDEN, RM BERNS, KI TI CHARACTERIZATION OF A PREFERRED SITE ON HUMAN CHROMOSOME-19Q FOR INTEGRATION OF ADENOASSOCIATED VIRUS-DNA BY NONHOMOLOGOUS RECOMBINATION SO EMBO JOURNAL LA English DT Article DE ADENOASSOCIATED VIRUS; CHROMOSOME-19; INTEGRATION; NONHOMOLOGOUS RECOMBINATION ID ADENOASSOCIATED VIRUS; V(D)J RECOMBINATION; DETROIT-6 CELLS; SIMIAN VIRUS-40; REPLICATION; GENE; SEQUENCES; MINISATELLITE; DELETION; GENOMES AB The human parvovirus, adeno-associated virus (AAV), has been shown to integrate preferentially into human chromosome 19 q13.3 - qter. The human target sequence for AAV integration (AAVS1) was cloned and sequenced. By analysis of the proviral junctions it was determined that integration of the AAV DNA occurred via a nonhomologous recombination pathway although there were either four or rive identical nucleotides at the junctions. Integration was a multistep, concerted process that resulted in cellular sequence rearrangements. The sequence of the integration locus was analyzed for possible recombination signals. Direct repeats at a much greater than random occurrence were found distributed non-uniformly throughout the AAVS1 sequence. A CpG island containing transcription factor binding site elements is suggestive of a TATA-less promoter. Evidence for transcriptional activity was provided by PCR amplification of reverse transcribed RNA. C1 GENET THERAPY INC,GAITHERSBURG,MD 20878. CORNELL UNIV,MED CTR,COLL MED,HEARST MICROBIOL RES CTR,DEPT MICROBIOL,NEW YORK,NY 10021. RP KOTIN, RM (reprint author), NIH,MOLEC HEMATOL BRANCH,BLDG 10,7D18,BETHESDA,MD 20892, USA. RI kotin, robert/B-8954-2008 FU NIAID NIH HHS [AI 22251] NR 46 TC 334 Z9 342 U1 2 U2 7 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC PY 1992 VL 11 IS 13 BP 5071 EP 5078 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KC837 UT WOS:A1992KC83700043 PM 1334463 ER PT J AU BACH, MA AF BACH, MA TI ANATOMY OF THE PITUITARY INSULIN-LIKE GROWTH-FACTOR SYSTEM SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; FACTOR-BINDING-PROTEINS; FOLLICULO-STELLATE CELLS; I GENE-EXPRESSION; RAT PITUITARY; TISSUE CONCENTRATIONS; NUCLEOTIDE-SEQUENCE; RECEPTOR GENE; SOMATOMEDIN-C; IGF-I AB In situ hybridization was used to map patterns of gene expression for components of the insulin-like growth factor (IGF) system, including IGF-I and -II, IGF-binding proteins 1-5 (IGFBP1-5), the IGF-I receptor, and GH in the rat pituitary. IGF-I mRNA was concentrated in isolated cells scattered throughout the gland with features typical of nonendocrine folliculo-stellate cells. IGF-II mRNA was abundant in neural (NL) and intermediate lobe (IL) capillaries, and low levels were present in endocrine cells of anterior lobe (AL) and IL. IGFBP1 mRNA was not detected in the pituitary. IGFBP2 mRNA was concentrated in epithelial cells lining AL follicles and in astroglial-like cells (pituicytes) of the NL. IGFBP3 mRNA was localized in isolated cells scattered throughout the AL and NL. IGFBP4 mRNA was relatively abundant in NL pituicytes and was diffusely expressed in the AL. IGFBP5 mRNA was equally abundant in NL and AL, and was localized in folliculo-stellate and epithelial cells of the AL and pituicytes and capillaries of the NL. Neither IGF-I nor IGFBP1-5 were detected in the IL. IGF-I receptor mRNA was abundant and homogeneously distributed throughout the AL and IL, compatible with expression by endocrine cells. There was overlap, but no particular correlation, between IGF system gene expression and GH-producing cells, which were clustered in the dorsal-lateral wings of the AL. In summary, IGF system gene expression is bountiful in the rat pituitary, but does not correlate with sites of GH synthesis. IGF-I receptor mRNA, which might have been expected to localize to somatotrophs, appears to be equally abundant in all of the endocrine cells of both AL and IL; the other constituents of the IGF system are localized in connective tissue and support elements that demonstrate no special anatomical relationship to somatotrophs. Finally, there is remarkably abundant gene expression for IGFBP2, -4, and -5 in the NL. RP BACH, MA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 34 TC 93 Z9 93 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 2588 EP 2594 DI 10.1210/en.131.6.2588 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800015 PM 1280202 ER PT J AU MULHERON, GW MULHERON, JG DANIELPOUR, D SCHOMBERG, DW AF MULHERON, GW MULHERON, JG DANIELPOUR, D SCHOMBERG, DW TI PORCINE GRANULOSA-CELLS DO NOT EXPRESS TRANSFORMING GROWTH-FACTOR-BETA-2 (TGF-BETA-2) MESSENGER-RIBONUCLEIC-ACID - MOLECULAR-BASIS FOR THEIR INABILITY TO PRODUCE TGF-BETA ACTIVITY COMPARABLE TO THAT OF RAT GRANULOSA-CELLS SO ENDOCRINOLOGY LA English DT Article ID ADULT TISSUES; CDNA CLONING; SEQUENCE; INVITRO; DIFFERENTIATION; PRECURSOR; CULTURE; EMBRYOS; TYPE-2; RNA AB In contrast to rat granulosa cells (GC), GC of the pig and cow produce very low levels of transforming growth factor-beta (TGF-beta)-like activity in vitro. Because cultured rat GC predominantly express TGF-beta2 messenger RNA (mRNA) and secrete high levels of the protein, we hypothesized that TGF-beta2 mRNA expression by porcine GC might be absent or diminished, thus providing a molecular explanation(s) for their relatively low levels of TGF-beta production. We tested this hypothesis by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay analysis. When analyzed by RT-PCR, porcine GC RNA from 1-3 mm follicles did not yield the expected 489 base pair (bp) TGF-beta2 product but instead generated a smaller than anticipated 240 bp species; porcine testis RNA generated both the 240 and the anticipated 489 bp products. Sequencing these species indicated that the smaller form was not a novel TGF-beta2 splice variant, and that the 489-bp product was porcine TGF-beta2. This is the first reported nucleotide sequence for porcine TGF-beta2; it is 90% and 91% identical to murine and human TGF-beta2 sequences, respectively. Further RT-PCR analysis of porcine GC RNA resulted in the identification of bp products representing TGF-beta1 and TGF-beta3 mRNA. Enzyme-linked immunosorbent assay analysis of porcine GC conditioned medium confirmed the presence of TGF-beta1 at very low levels. TGF-beta2 was undetectable. Comparable analysis of GC from the diethylstilbestrol-treated prepubertal rat demonstrated the presence of TGF-beta1 and TGF-beta3 mRNA by RT-PCR and very low levels of the corresponding protein products in conditioned culture medium. Collectively, these results suggest that the inability of porcine GC to express TGF-beta2 mRNA could explain the very low levels of TGF-beta activity secreted by these cells in vitro. C1 DUKE UNIV, MED CTR, DEPT OBSTET GYNECOL, BOX 3323, DURHAM, NC 27710 USA. DUKE UNIV, MED CTR, DEPT CELL BIOL, DURHAM, NC 27710 USA. DUKE UNIV, MED CTR, CTR COMPREHENS CANC, DURHAM, NC 27710 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD-07315, HD-11827] NR 22 TC 19 Z9 19 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 2609 EP 2614 DI 10.1210/en.131.6.2609 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800018 PM 1280203 ER PT J AU CIZZA, G BRADY, LS CALOGERO, AE BAGDY, G LYNN, AB KLING, MA BLACKMAN, MR CHROUSOS, GP GOLD, PW AF CIZZA, G BRADY, LS CALOGERO, AE BAGDY, G LYNN, AB KLING, MA BLACKMAN, MR CHROUSOS, GP GOLD, PW TI CENTRAL HYPOTHYROIDISM IS ASSOCIATED WITH ADVANCED AGE IN MALE FISCHER 344/N RATS - INVIVO AND INVITRO STUDIES SO ENDOCRINOLOGY LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; PLASMA GROWTH-HORMONE; FREE-THYROXINE INDEX; THYROID-HORMONE; AGING RATS; PARAVENTRICULAR NUCLEUS; FEEDBACK SUPPRESSION; LOCUS COERULEUS; LEVELS DECREASE; TSH SECRETION AB We investigated age-related alterations in hypothalamic-pituitary-thyroid function in a series of in vivo and in vitro studies in 2-, 8-, 18-, and 24-month-old male Fischer 344/N (F344/N) rats. Thyroid histology showed progressive follicular loss with advancing age; this was associated with significant and progressive decrements in plasma levels of free T4 and free T3, but not immunoreactive TSH, which remained unchanged with age. This was accompanied by a progressive age-dependent loss in in vivo responsivity of the thyrotroph to synthetic TRH and a paradoxically augmented response of GH to this peptide in the oldest rats. Steady state levels of prepro-TRH mRNA in the hypothalamic paraventricular nucleus were decreased with age, whereas TRH content in and in vitro secretion by whole hypothalami remained unchanged. Both anterior pituitary steady state TSH beta-subunit mRNA levels and TSH content were decreased with age. Taken together, these data suggest that aging in male F344/N rats is associated with a progressive, centrally mediated decrease in thyroid function. The relative contributions to this phenomenon of age-related alterations in suprahypothalamic and/or hypothalamic vs. pituitary thyrotropic function remain to be determined, as do the relationships between changes in hypothalamic-pituitary-thyroid function and those in aging per se. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIA, GERONTOL RES CTR, BALTIMORE, MD 20224 USA. RP CIZZA, G (reprint author), NIMH, CLIN NEUROENDOCRINOL BRANCH, BLDG 10, ROOM 3S-235, BETHESDA, MD 20892 USA. RI Kling, Mitchel/F-4152-2010; OI Kling, Mitchel/0000-0002-2232-1409; Bagdy, Gyorgy/0000-0001-8141-3410 NR 60 TC 33 Z9 33 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 2672 EP 2680 DI 10.1210/en.131.6.2672 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800028 PM 1446609 ER PT J AU ISOZAKI, O EMOTO, N TSUSHIMA, T SATO, Y SHIZUME, K DEMURA, H AKAMIZU, T KOHN, LD AF ISOZAKI, O EMOTO, N TSUSHIMA, T SATO, Y SHIZUME, K DEMURA, H AKAMIZU, T KOHN, LD TI OPPOSITE REGULATION OF DEOXYRIBONUCLEIC-ACID SYNTHESIS AND IODIDE UPTAKE IN RAT-THYROID CELLS BY BASIC FIBROBLAST GROWTH-FACTOR - CORRELATION WITH OPPOSITE REGULATION OF C-FOS AND THYROTROPIN RECEPTOR GENE-EXPRESSION SO ENDOCRINOLOGY LA English DT Article ID FACTOR-I; TYROSINE KINASE; FRTL-5 CELLS; THYMIDINE INCORPORATION; RIBONUCLEIC-ACID; PROTO-ONCOGENE; INSULIN; DIFFERENTIATION; SERUM; ADENOSINE-3',5'-MONOPHOSPHATE AB Basic fibroblast growth factor (bFGF) increases DNA synthesis in rat FRTL-5 thyroid cells, as measured by increased incorporation of tritiated thymidine into DNA. We show that this action is associated with the ability of bFGF to increase cytosolic Ca2+ levels and transiently increase c-fos mRNA levels. Other agents that increase c-fos mRNA levels and DNA synthesis in FRTL-5 cells include TSH, insulin, insulin-like growth factor-I, phorbol esters, A23187, and alpha1-adrenergic agents; the last two agents also act by increasing cytosolic Ca2+ levels. Despite its enhancement of DNA synthesis, however, bFGF decreases TSH-induced cAMP-mediated iodide uptake. This action appears to reflect two separate actions of bFGF. First, bFGF decreases TSH receptor mRNA levels and the ability of TSH to acutely increase cAMP levels in FRTL-5 cells. The ability of bFGF to negatively regulate TSH receptor mRNA levels is additive to and independent of the ability of TSH and its cAMP signal to negatively autoregulate TSH receptor mRNA levels. This is consistent with the effect of bFGF on cytosolic Ca2+ levels and the ability of increased cytosolic Ca2+ to decrease TSH receptor mRNA levels. Second, bFGF inhibits cAMP signal expression, as evidenced by its ability to inhibit (Bu)2cAMP-induced iodide uptake in FRTL-5 cells. Both effects are, presumably, associated with the ability of bFGF to counteract TSH/cAMP-induced increases in thyroid peroxidase mRNA levels, which we demonstrate. We suggest, therefore, that bFGF causes opposite effects on DNA synthesis and iodide uptake because of its effect on cytosolic Ca2+ levels and because increases in cytosolic Ca2+ can have opposite effects on gene transcription, particularly in the case of the TSH receptor and c-fos genes. C1 INST GROWTH SCI, TOKYO 162, JAPAN. NIDDKD, BIOCHEM & METAB LAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. RP ISOZAKI, O (reprint author), TOKYO WOMENS MED COLL, INST CLIN ENDOCRINOL, DEPT MED, 8-1 KAWADA CHO, SHINJUKU KU, TOKYO 162, JAPAN. NR 54 TC 29 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 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 2723 EP 2732 DI 10.1210/en.131.6.2723 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800035 PM 1332847 ER PT J AU CIAMPANI, T FABBRI, A ISIDORI, A DUFAU, ML AF CIAMPANI, T FABBRI, A ISIDORI, A DUFAU, ML TI GROWTH HORMONE-RELEASING HORMONE IS PRODUCED BY RAT LEYDIG-CELL IN CULTURE AND ACTS AS A POSITIVE REGULATOR OF LEYDIG-CELL FUNCTION SO ENDOCRINOLOGY LA English DT Article ID VASOACTIVE INTESTINAL PEPTIDE; MESSENGER-RIBONUCLEIC-ACID; ADENYLATE-CYCLASE; VIP RECEPTORS; BINDING-SITES; PROENKEPHALIN GENE; SERTOLI CELLS; FACTOR-I; TESTIS; EXPRESSION AB Rat GH-releasing hormone (GHRH), mainly contained in hypothalamic neurons, has also been identified in several extraneural tissues, including the gastrointestinal tract, placenta, ovary, and testis. In the testis, GHRH mRNA is ontogenically regulated, and GHRH immunoreactivity can be observed in interstitial cells and tubules, suggesting an intratesticular role for the peptide. Leydig cells in culture are able to produce hypothalamic releasing hormones, i.e. CRH, which acts as an autocrine negative regulator of Leydig cell function. In this study we investigated whether GHRH is present in Leydig cells and evaluated the role of the peptide in Leydig cell function. Adult Leydig cells in culture produced considerable amounts of immunoreactive GHRH [23.9 +/- 2.1 (+/-SE) pg/10(6) cells.30 min], and the release of the peptide was acutely stimulated by hCG. HPLC analysis of GHRH in media from basal and hCG-treated cultures showed the presence of a single peak eluting at the same retention time as that of hypothalamic rat GHRH. Radioligand binding and activation studies revealed a common receptor for vasoactive intestinal peptide (VIP) and rat GHRH in Leydig cell membrane. Specific binding of [I-125]VIP to Leydig cell membranes showed the presence of a single site, with high affinity and low binding capacity. The relative potencies of VIP-related peptides for inhibition of radioligand binding were: VIP > rat GHRH > secretin > human GHRH. In cultured Leydig cells, GHRH and VIP stimulated cAMP production, consistent with coupling of the receptor to the adenylate cyclase system. VIP displayed a lower ED50 than GHRH in stimulating cAMP production (P < 0.01), comparable with the higher binding potency of this peptide. No additive effects of VIP- and GHRH-stimulated cAMP generation were observed, suggesting that both peptides compete for the same receptor protein. GHRH and VIP had no effect on basal steroidogenesis, indicating a lack of tonic actions and compartmentalization of the peptides' effect. On the other hand, GHRH acted as a potentiator of the acute gonadotropin stimulation of testosterone production and cAMP generation. [I-125]hCG binding to the Leydig cells in culture showed that GHRH was unable to affect the number or affinity of binding sites for hCG, indicating that the GHRH-sensitizing effect on LH action is beyond the level of gonadotropin binding and possibly is through the facilitation of LH receptor coupling functions. These studies demonstrate that authentic rat GHRH is actively released from Leydig cells in culture, is under gonadotropin control, and acts via a VIP receptor as a direct stimulator of Leydig cell function and/or facilitator of LH-induced cAMP production and steroidogenesis. Because GHRH also stimulates basal and FSH-stimulated Sertoli cell functions, we conclude that testicular GHRH is an autocrine/paracrine positive regulator of male gonadal function. C1 NICHHD, ENDOCRINOL REPROD RES BRANCH,MOLEC ENDOCRINOL SECT, BLDG 10,B1-L400, BETHESDA, MD 20892 USA. UNIV ROME LA SAPIENZA, DEPT ANDROL, I-00185 ROME, ITALY. NR 57 TC 59 Z9 61 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 2785 EP 2792 DI 10.1210/en.131.6.2785 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800043 PM 1332849 ER PT J AU SHEMER, J ADAMO, ML ROBERTS, CT LEROITH, D AF SHEMER, J ADAMO, ML ROBERTS, CT LEROITH, D TI TISSUE-SPECIFIC TRANSCRIPTION START SITE USAGE IN THE LEADER EXONS OF THE RAT INSULIN-LIKE GROWTH FACTOR-I GENE - EVIDENCE FOR DIFFERENTIAL REGULATION IN THE DEVELOPING KIDNEY SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; IGF-I; RNAS; EXPRESSION; SEQUENCE; ASSOCIATION; INITIATION; REGIONS; SERUM; BRAIN AB The production of insulin-like growth factor-I (IGF-I) in extrahepatic tissues supports both autocrine and paracrine functions and is regulated differently from that in liver, which supports endocrine function. In rat liver, transcription initiation primarily occurs at four distinct, widely separated sites in exon 1 of the IGF-I gene, whereas in exon 2, transcription initiation occurs at a cluster of sites. To understand the molecular basis for tissue-specific regulation of IGF-I gene expression, we have mapped transcription start site usage in the following extrahepatic tissues: testes, lung, kidney, heart, brain, muscle, and stomach, with liver serving as a control. In adult rats, kidney and brain exhibited a pattern of exon 1 transcription similar to that seen in liver, i.e. roughly equivalent use of start sites 2 and 3. In contrast, testes and lung preferentially used start site 3, while stomach, heart, and muscle predominately used start site 3. Start sites 1 and 4 were used in all tissues at extremely low levels. In those tissues studied in which exon 2 transcripts are expressed (testes, lung, stomach, and kidney), the pattern of exon 2 transcription initiation was identical to that in adult rat liver. During postnatal development, the use of all transcription start sites in exons 1 and 2 was coordinate in lung and stomach. Selection of transcription start sites in the kidney, on the other hand, was subject to regulation during postnatal development. Specifically, within exon 1, start site 3 was expressed constitutively throughout peri- and postnatal development. In contrast, the usage of start site 2 was not detected at late fetal or early postnatal stages, but appeared and rapidly increased only at the stage of weaning. Exon 2 transcripts in kidney also did not appear until the postnatal period. These data suggest tissue-specific and developmentally regulated transcription factors regulating IGF-I promoter activity or, alternatively, tissue-specific and developmental stage-dependent differences in the stability of IGF-I mRNAs resulting from the use of different transcription start sites. These different mRNAs may be of significance in the differential regulation of IGF-I production for autocrine or paracrine function. C1 NIDDKD, DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT, BLDG 10,ROOM 8S243, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 NR 27 TC 61 Z9 61 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 2793 EP 2799 DI 10.1210/en.131.6.2793 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800044 PM 1446616 ER PT J AU BENVENGA, S CAHNMANN, HJ RADER, D KINDT, M ROBBINS, J AF BENVENGA, S CAHNMANN, HJ RADER, D KINDT, M ROBBINS, J TI THYROXINE BINDING TO THE APOLIPOPROTEINS OF HIGH-DENSITY-LIPOPROTEINS HDL(2) AND HDL(3) SO ENDOCRINOLOGY LA English DT Article ID IMMUNOSORBENT-ASSAY ELISA; A-I; MONOCLONAL-ANTIBODY; THYROID-HORMONES; PLASMA; IDENTIFICATION; FIBROBLASTS; METABOLISM; PROTEIN; CELLS AB Four preparations of high density lipoprotein HDL2, five of HDL3, and purified apolipoproteins apoA-I, apoA-IV, and apoE were photoaffinity labeled with [I-125]T4 and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Gels were also immunoblotted with antiserum against apoA-I, apoA-II, apoA-IV, apoE, or apo(a), and the immunostained membrane was then autoradiographed. In HDL2, the two major radioactive bands migrated near the origin of the resolving gel and at 28-31 kilodaltons (kDa). The first band, stained by anti-apo(a) and anti-apoB-100, accounted for 40-96% of the total radioactivity and was attributed to lipoprotein(a), which is isolated in the same density range as HDL2. The second band, stained by anti-apoA-I, accounted for 1-57% [41-95% after correction for contaminating lipoprotein(a)] of the [I-125]T4 in the resolving gel. In HDL3, the major radioactive band was identified as apoA-I and contained 93-94% of the [I-125]T4 in the resolving gel. Minor radioactive bands in both HDL2 and HDL3 were identified as apoA-II (17-18 kDa), apoA-II monomer (7-10 kDa), apoE (36-38 kDa), and apoAII-apoE heterodimer (46 kDa). In addition, HDL3 contained apoA-IV (43 kDa). Photoaffinity labeling of isolated apoA-IV and apoE showed that each protein interacted with [I-125]T4. In both HDL2 and HDL3, photoaffinity labeling in the presence of unlabeled L-T4 (1-10 mum) showed inhibition, suggesting a K(d) in the micromolar range. This inhibition varied among different apo bands of the same HDL2 or HDL3 preparation and among the same bands of different preparations. Labeling in the presence of heparin or other inhibitors of T4 binding to plasma proteins (furosemide, diclofenac, and mefenamic acid) showed that HDL2-associated apoA-I was more sensitive to inhibition than HDL3-associated apoA-I. In conclusion, 1) HDL2 and HDL3 carry T4 mainly through apoA-I and secondarily through apoA-II and apoE. The inter- and intrasubclass variations in T4 binding and sensitivity to inhibitors can be explained by the known heterogeneity of HDL particles and possible differences in conformation of the apo. The findings reported here, that apo other than apoA-I and apoB exhibit saturable binding of T4, suggest that thyroid hormone-lipoprotein interactions may have even wider physiological implications than previously appreciated. C1 NIDDKD, GENET & BIOCHEM BRANCH, BLDG 10, ROOM 8N315, BETHESDA, MD 20892 USA. NHLBI, MOLEC DIS BRANCH, BETHESDA, MD 20892 USA. UNIV MESSINA, SCH MED, I-98125 MESSINA, ITALY. NR 29 TC 15 Z9 16 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 2805 EP 2811 DI 10.1210/en.131.6.2805 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800046 PM 1446618 ER PT J AU STOJILKOVIC, SS IIDA, T CESNJAJ, M CATT, KJ AF STOJILKOVIC, SS IIDA, T CESNJAJ, M CATT, KJ TI DIFFERENTIAL ACTIONS OF ENDOTHELIN AND GONADOTROPIN-RELEASING-HORMONE IN PITUITARY GONADOTROPHS SO ENDOCRINOLOGY LA English DT Article ID NEUROHYPOPHYSEAL HORMONES; CALCIUM OSCILLATIONS; SECRETORY RESPONSES; CYTOSOLIC CALCIUM; RECEPTORS; CELLS; DESENSITIZATION; MOBILIZATION; INACTIVATION; TRANSIENTS AB Endothelin (ET) and GcRH act through specific receptors to promote Ca2+ mobilization and influx pathways in pituitary gonadotrophs. In the present study cytoplasmic calcium ([Ca2+]i) and secretory responses to these two agonists are compared. In single gonadotrophs, low concentrations of both agonists cause oscillatory [Ca2+]i responses after a latent period. Such responses usually consist of discrete transients arising from the normal resting level, but are sometimes super-imposed imposed on an elevated basal calcium level. At high doses, ET-1 and GnRH induce biphasic responses, composed of a spike phase followed by a plateau that often shows high frequency and low amplitude Ca2+ transients. The duration of the latent period and the frequency of the subsequent oscillations are correlated, and both are dependent on agonist concentration. The frequencies and amplitudes of Ca2+ spiking are also interrelated, increases in frequency are followed by more rapid decreases in the amplitude of the Ca2+ transients. After K+-induced depolarization, gonadotrophs retain their oscillatory Ca" responses to ET-1 and GnRH, with the same frequency as controls. Activation of protein kinase-C by phorbol esters does not alter the frequency of ET-induced Ca2+ transients, but significantly reduces their amplitudes. In contrast, treatment with nanomolar concentrations of thapsigargin converts ET-induced oscillations into a biphasic response, suggesting that Ca2+-ATPase in the endoplasmic reticulum participates in the oscillatory mechanism. The two agonists differ in their threshold doses and concentration dependence, ET being significantly less potent than GnRH. Also, gonadotrophs stimulated by ET-1 exhibit different post-treatment responsiveness than those exposed to GnRH. While GnRH-treated cells recover their full [Ca2+]i and secretory responses within 30 min as well as normal [Ca2+]i and secretory responses to ET-1, endothelin-treated cells are refractory to further stimulation with ET and exhibit either attenuated or enhanced Ca2+ and LH responses to GnRH, depending on the duration of exposure to ET-1 and the subsequent recovery period. These data indicate that both receptors use the same mechanism(s) for Ca2+ release, but have different capacities to generate, maintain, and reinitiate the Ca2+ signal. RP STOJILKOVIC, SS (reprint author), NICHHD, ENDOCRINOL & REPROD RES BRANCH, BLDG 10, ROOM B1-L400, BETHESDA, MD 20892 USA. NR 33 TC 24 Z9 24 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 2821 EP 2828 DI 10.1210/en.131.6.2821 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800048 PM 1446620 ER PT J AU SCHOEN, TJ BEEBE, DC CLEMMONS, DR CHADER, GJ WALDBILLIG, RJ AF SCHOEN, TJ BEEBE, DC CLEMMONS, DR CHADER, GJ WALDBILLIG, RJ TI LOCAL SYNTHESIS AND DEVELOPMENTAL REGULATION OF AVIAN VITREAL INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS - A MODEL FOR INDEPENDENT REGULATION IN EXTRAVASCULAR AND VASCULAR COMPARTMENTS SO ENDOCRINOLOGY LA English DT Article ID FACTOR (IGF)-BINDING PROTEIN; FACTOR-II GENE; MIDGESTATIONAL RAT EMBRYO; IGF-I; HUMAN-FETUS; EXPRESSION PATTERN; SERUM; RECEPTORS; SOMATOMEDIN; CHICKEN AB The expression and regulation of insulin-like growth factor-binding proteins (IGFBPs) in developing avian vitreous humor and serum were compared. Vitreal IGF-I-binding activity was highest on embryonic day 6 [E-6; bound/free ratio (B/F), 0.22 +/- 0.019/50 mul), decreased 10-fold between E-6 and E-19, and then remained stable through the remainder of embryonic development. In contrast, serum IGF-I binding increased 2-fold over this period, from a B/F of 0.380 +/- 0.056 (E-6) to a B/F of 0.89 +/- 0.18 (E-19). After hatching, serum IGF-I-binding activity continued to increase through posthatching week 12, while vitreal IGF-I binding increased only slightly and then remained constant. Although IGF-II binding in the vitreous humor and rerum is 2- to 3-fold higher than that of IGF-I, the same pattern of developmental regulation was observed as with IGF-I. Western ligand blots revealed a vitreal 24-kilodalton (kDa) IGFBP that was absent from both embryonic and adult sera. Likewise, posthatching serum was found to contain a 70-kDa IGFBP absent in vitreous humor. Deglycosylation of vitreal and serum IGFBPs followed by Western ligand blotting revealed unique glycosylation patterns for vitreal and serum IGFBPs. One of the IGFBPs that is differentially glycosylated in vitreous and serum is a 33-kDa IGFBP that is precipitated with human IGFBP-2 antiserum. Northern blot analysis revealed the presence of IGFBP-2 mRNA in several embryonic ocular tissues as well as liver. The observations that vitreal and serum IGFBP levels are independently regulated during development and that IGFBPs from these two compartments have different molecular weights and glycosylation patterns suggest that the vitreal IGFBPs are not derived from serum. The presence of IGFBP-2 mRNA in ocular tissue surrounding the vitreal chamber supports the view that certain vitreal IGFBPs may be synthesized locally. C1 NEI, RETINAL CELL & MOLEC BIOL LAB, ROOM 304, BLDG 6, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT ANAT & CELL BIOL, BETHESDA, MD 20814 USA. UNIV N CAROLINA, SCH MED, DIV ENDOCRINOL, CHAPEL HILL, NC 27599 USA. NR 48 TC 49 Z9 49 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 2846 EP 2854 DI 10.1210/en.131.6.2846 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800051 PM 1280206 ER PT J AU CHIN, E ZHOU, J BONDY, CA AF CHIN, E ZHOU, J BONDY, CA TI RENAL GROWTH-HORMONE RECEPTOR GENE-EXPRESSION - RELATIONSHIP TO RENAL INSULIN-LIKE GROWTH-FACTOR SYSTEM SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; SERUM BINDING-PROTEIN; FACTOR-I; SOMATOMEDIN-C; PI TRANSPORT; IGF-I; RAT; TISSUE; RNA; SECRETION AB In order to elucidate potential sites of direct GH action on the kidney, we used in situ hybridization to localize GH receptor (GHR) gene expression during the course of development and in the adult rat. In order to illuminate potential interactions between GH and insulin-like growth factor-I (IGF-I) in regulating renal function, we compared the anatomical localization of GHR messenger RNA (mRNA) with that for the IGF-I receptor and for IGF-I in the rat kidney. Low levels of GHR mRNA were present in the kidney from before birth and increased in abundance until postnatal day 40. Hypophysectomy resulted in a decrease and GH treatment resulted in an increase in renal GHR mRNA levels. Renal GHR mRNA was most abundant in the proximal straight tubule, with lesser levels present in the medullary thick ascending limb (MTAL), and it was not detected in the glomerulus or inner medulla. In contrast, IGF-I receptor mRNA was concentrated in the glomerulus, distal nephron, and collecting system. The only point of convergence for GHR and IGF-I receptor mRNAs was in the MTAL, where IGF-I mRNA was localized. This segregation of GHR and IGF-I receptor gene expression in the kidney suggests that each hormone has distinct spheres of action along the nephron, with GH acting directly on the proximal straight tubule, whereas IGF-I may act on the glomerulus, distal nephron, and collecting duct. GHR expression in the MTAL, which is the site of renal IGF-I synthesis, supports the view that GH has a direct effect on renal IGF-I synthesis. Finally, it appears that in the kidney, as in other GH-sensitive tissues, GH may regulate its receptor levels. RP CHIN, E (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 26 TC 56 Z9 57 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 3061 EP 3066 DI 10.1210/en.131.6.3061 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800080 PM 1446640 ER PT J AU RADHAKRISHNAN, B OKE, BO PAPADOPOULOS, V DIAUGUSTINE, RP SUAREZQUIAN, CA AF RADHAKRISHNAN, B OKE, BO PAPADOPOULOS, V DIAUGUSTINE, RP SUAREZQUIAN, CA TI CHARACTERIZATION OF EPIDERMAL GROWTH-FACTOR IN MOUSE TESTIS SO ENDOCRINOLOGY LA English DT Article ID RAT SERTOLI CELLS; FACTOR RECEPTOR; SUBMANDIBULAR-GLAND; FACTOR PRECURSOR; LEYDIG-CELLS; FACTOR-ALPHA; IMMUNOCYTOCHEMICAL LOCALIZATION; REPRODUCTIVE FUNCTION; PLASMA-MEMBRANE; KIDNEY AB Considerable evidence exists to suggest that epidermal growth factor (EGF) influences spermatopnesis directly. The tissue source of this EGF, however, is not yet clear. In this study we examine whether the testis itself can serve as a source of EGF. Gel filtration fractions of acid extracted testes exhibited the ability to displace I-125-EGF from testis membranes. The testicular fractions containing the I-125-EGF displacement activity coeluted within the same range as those of submandibular gland (SG) fractions containing mature EGF and prepared in an identical fashion. Next, we employed specific antisera probes to investigate first, whether the testis synthesizes this EGF displacement activity and second, to determine the cell distribution of the testicular EGF. Two types of antisera probes were employed: 1) commercially available antisera to mature EGF (EGF(m)), i.e. the 6,000 M(r) peptide, and 2) polypeptide specific antisera to the C-terminus of the EGF precursor (EGF(p)), i.e. the 140,000 M(r) integral membrane molecule which exhibits seven EGF-like repeats in addition to the EGF(m). Metabolic labeling of testis with S-35-methionine was performed, followed by immunoprecipitation with the anti-EGF. antisera. Parallel studies using kidney and SG were used as positive controls. Fluorograms exhibited a prominent band at M(r) 140,000 for testis and kidney, corresponding to the EGF(p). There was, in addition, a M(r) 50,000 band present for the testis. In SG, a band at M(r) 6,000, corresponding to EGF(m), in addition to bands at M(r) 21,000 and 46,000 were observed also. Immunoblotting of testis, kidney, and SG membrane preparations with the specific antisera to either the EGF(m) or EGF(p) also resulted in identifying the EGF(p) at M(r) 140,000, as well as other lower mol wt bands. Preadsorption of anti-EGF(m) antisera with excess EGF(m) eliminated all of the specific bands that were immunoblotted. Peroxidase immunocytochemistry of testis, kidney, and SG was also performed using the specific antisera to either EGF(m) or EGF(p). EGF(p) and EGF(m) staining in SG and kidney was identical to previously published results in which the distribution of EGF(m) in these tissues was established. In testis, EGF(m) immunostaining showed positive results in Sertoli cells, pachytene spermatocytes and round spermatids. In contrast, EGF(p) immunostaining was limited to pachytene spermatocytes and round spermatids. These results suggest that the testis must now be included in the list of tissues capable of synthesizing EGF(p). Specifically, EGF(p) synthesis appears limited to the post meiotic germ cells. C1 GEORGETOWN UNIV, SCH MED, DEPT ANAT & CELL BIOL, 3900 RESERVOIR RD NW, WASHINGTON, DC 20007 USA. NIEHS, HORMONE & CANC WORKGRP, RES TRIANGLE PK, NC 27709 USA. OI Papadopoulos, Vassilios/0000-0002-1183-8568 FU NICHD NIH HHS [HD-23484] NR 56 TC 38 Z9 42 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1992 VL 131 IS 6 BP 3091 EP 3099 DI 10.1210/en.131.6.3091 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB068 UT WOS:A1992KB06800084 PM 1446643 ER PT J AU CHROUSOS, GP AF CHROUSOS, GP TI REGULATION AND DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS - THE CORTICOTROPIN-RELEASING HORMONE PERSPECTIVE SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; POTENTIAL CLINICAL IMPLICATIONS; POSTTRAUMATIC-STRESS-DISORDER; FACTOR-LIKE IMMUNOREACTIVITY; MESSENGER-RNA LEVELS; SECRETION INVITRO; CUSHINGS-SYNDROME; STIMULATION TEST; ANTERIOR-PITUITARY; BETA-ENDORPHIN C1 NICHHD,PEDIAT ENDOCRINOL SECT,BETHESDA,MD 20892. NR 134 TC 115 Z9 119 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD DEC PY 1992 VL 21 IS 4 BP 833 EP 856 PG 24 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LA543 UT WOS:A1992LA54300005 PM 1486878 ER PT J AU NIMS, RW BEEBE, LE DRAGNEV, KH THOMAS, PE FOX, SD ISSAQ, HJ JONES, CR LUBET, RA AF NIMS, RW BEEBE, LE DRAGNEV, KH THOMAS, PE FOX, SD ISSAQ, HJ JONES, CR LUBET, RA TI INDUCTION OF HEPATIC CYP1A IN MALE F344/NCR RATS BY DIETARY EXPOSURE TO AROCLOR-1254 - EXAMINATION OF IMMUNOCHEMICAL, RNA, CATALYTIC, AND PHARMACOKINETIC END-POINTS SO ENVIRONMENTAL RESEARCH LA English DT Article ID SYNTHETIC OLIGODEOXYRIBONUCLEOTIDE PROBES; POLYCHLORINATED BIPHENYL CONGENERS; LIVER-MICROSOMES; CYTOCHROME-P-450 ISOZYMES; AROMATIC-HYDROCARBONS; NUCLEOTIDE-SEQUENCE; FLUOROMETRIC ASSAY; 8 ISOZYMES; PCBS; QUANTITATION C1 RUTGERS STATE UNIV,COLL PHARM,PISCATAWAY,NJ 08855. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. RP NIMS, RW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 46 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD DEC PY 1992 VL 59 IS 2 BP 447 EP 466 DI 10.1016/S0013-9351(05)80048-9 PG 20 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA KF839 UT WOS:A1992KF83900014 PM 1281448 ER PT J AU BOINSKI, S MITCHELL, CL AF BOINSKI, S MITCHELL, CL TI ECOLOGICAL AND SOCIAL-FACTORS AFFECTING THE VOCAL BEHAVIOR OF ADULT FEMALE SQUIRREL-MONKEYS SO ETHOLOGY LA English DT Article ID SAIMIRI-SCIUREUS; CALLS; VOCALIZATIONS; MACAQUE; FORM AB Focal recordings of the vocalizations of squirrel monkeys, Saimiri sciureus, occupying an undisturbed Peruvian habitat were collected to evaluate the importance of both the ecological and social functions of female vocal behavior. The rates and sequences of six call types were examined by context: single, double, and multiple chuck, peep, tweet, and tweet-chuck. In contrast to laboratory studies, our findings emphasize the primacy of ecological functions in the wild, where calling permits females to operate as a convoy of spatially separated individuals in an arboreal habitat where visual contact is limited. Chuck calls are probably best interpreted as contact calls. The rate of chucks and tweet-chucks increased when the nearest adult female was > 5 m away. However, call production did not predict a change in the spatial separation between a female and her nearest adult female. During travel, the rate of single and double chucks was greater and the rate of multiple chucks was reduced. No direct relationship was found between foraging activities and vocal behavior. Although secondary, social factors did have a subtle effect on vocal behavior: the larger the social alliance of a female, the lower the rate and repetitiveness of her chuck vocalizations. We also consider the role of variations in vocalization rates among primates and the differing conclusions of field and captive studies of squirrel monkey vocal behavior. C1 NICHHD,NIH ANIM CTR,COMPARAT ETHOL LAB,POOLESVILLE,MD. PRINCETON UNIV,DEPT ECOL & EVOLUT BIOL,PRINCETON,NJ 08544. NR 46 TC 33 Z9 34 U1 1 U2 14 PU BLACKWELL WISSENSCHAFTS-VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0179-1613 J9 ETHOLOGY JI Ethology PD DEC PY 1992 VL 92 IS 4 BP 316 EP 330 PG 15 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA KE805 UT WOS:A1992KE80500005 ER PT J AU REITH, MEA DECOSTA, B RICE, KC JACOBSON, AE AF REITH, MEA DECOSTA, B RICE, KC JACOBSON, AE TI EVIDENCE FOR MUTUALLY EXCLUSIVE BINDING OF COCAINE, BTCP, GBR-12935, AND DOPAMINE TO THE DOPAMINE TRANSPORTER SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE [H-3]CFT (2-BETA-CARBOMETHOXY-3-BETA-(4-FLUOROPHENYL)-TROPANE) BINDING; COCAINE; BTCP (N[1-(2-BENZO[B]THIOPHENYL)CYCLOHEXYL]PIPERIDINE); GBR-12935; DOPAMINE UPTAKE INHIBITORS; STRIATUM (RAT) ID SEROTONIN TRANSPORTER; RADIOLIGAND BINDING; LOCAL-ANESTHETICS; MAZINDOL BINDING; UPTAKE CARRIER; UPTAKE COMPLEX; H-3 MAZINDOL; UPTAKE SITES; RAT-BRAIN; CLONING AB The present study addressed the possibility that there are distinct but allosterically interacting populations of binding sites for dopamine / cocaine and BTCP / GBR (N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine/ 1-(2-diphenylmethoxy)-ethyl]-4-(3-phenylpropyl)piperazine) (selective dopamine uptake blockers) on the dopamine transporter in the rat striatum. Dopamine uptake sites were labeled in vitro with the cocaine analog [H-3]CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane), and the inhibition of binding by CFT or cocaine was measured. A graphic method was adopted for studying shifts in inhibitory potency resulting from the addition of a second compound. Under the conditions used, the co-presence of dopamine, GBR 12935, or BTCP decreased the inhibitory potency of CFT or cocaine to the extent predicted by a model in which all compounds bind to the same site or the binding of all compounds is mutually exclusive. No evidence for negative allosteric interactions between CFT and BTCP was found in experiments comparing inhibition of [H-3]CFT binding by BTCP at a low and high concentration of [H-3]CFT. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP REITH, MEA (reprint author), UNIV ILLINOIS,COLL MED,DEPT BASIC SCI,BOX 1649,PEORIA,IL 61656, USA. RI Reith, Maarten/A-4601-2008 FU NIDA NIH HHS [DA 03025] NR 43 TC 71 Z9 71 U1 1 U2 2 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 DEC 1 PY 1992 VL 227 IS 4 BP 417 EP 425 DI 10.1016/0922-4106(92)90160-W PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KA025 UT WOS:A1992KA02500009 PM 1446712 ER PT J AU COHEN, RM SEMPLE, WE GROSS, M KING, AC NORDAHL, TE AF COHEN, RM SEMPLE, WE GROSS, M KING, AC NORDAHL, TE TI METABOLIC BRAIN PATTERN OF SUSTAINED AUDITORY-DISCRIMINATION SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE ATTENTION; BASAL GANGLIA; FRONTAL CORTEX; CINGULATE; TEMPORAL LOBE; HUMAN ID POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; CAUDATE-NUCLEUS; ATTENTION; DOPAMINE; SCHIZOPHRENIA; DEPLETION; NEURONS; NEGLECT; CORTEX AB Positron emission tomography of [F-18]-2-fluorodeoxyglucose was used to assess the functional brain activity of normal subjects while performing auditory discrimination (CPT), while receiving an identical set of tones as in CPT, but with the instructions that they were background noise, or while at rest. The present study: (1) confirms earlier findings of an association between the functional activity of the right midprefrontal cortex and the performance of auditory discrimination, (2) localizes this increase in right prefrontal cortex activity to the middle prefrontal gyrus; and (3) provides a framework of specific testable hypotheses for the evaluation of the importance of certain limbic and paralimbic areas in the biological determination of sustained attention to be addressed in future studies. The framework accounts for the now confirmed finding that the middle cingulate has lower metabolic activity in CPT than at rest, and new findings of alterations in temporal lobe processing of tones in response to attention. RP COHEN, RM (reprint author), NIMH,IRP,LCM,CLIN BRAIN IMAGING SECT,BLDG 10-4N317,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 34 TC 71 Z9 71 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD DEC PY 1992 VL 92 IS 1 BP 165 EP 172 PG 8 WC Neurosciences SC Neurosciences & Neurology GA KB313 UT WOS:A1992KB31300015 PM 1486951 ER PT J AU CHUNG, DL JORAN, A FRIEDMAN, F ROBINSON, R BRANDTRAUF, PW WEINSTEIN, IB RONAI, Z BASKIN, L DYKES, DC MURPHY, RB NISHIMURA, S YAMAIZUMI, Z PINCUS, MR AF CHUNG, DL JORAN, A FRIEDMAN, F ROBINSON, R BRANDTRAUF, PW WEINSTEIN, IB RONAI, Z BASKIN, L DYKES, DC MURPHY, RB NISHIMURA, S YAMAIZUMI, Z PINCUS, MR TI EVIDENCE THAT OOCYTE MATURATION INDUCED BY AN ONCOGENIC RAS-P21 PROTEIN AND INSULIN IS MEDIATED BY OVERLAPPING YET DISTINCT MECHANISMS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID MURINE SARCOMA-VIRUS; BINDING DOMAIN; H-RAS; GENE; MUTANTS; P21RAS; CELLS; TRANSFORMATION; EXPRESSION; INHIBITION C1 SUNY HLTH SCI CTR,DEPT PATHOL,750 E ADAMS ST,SYRACUSE,NY 13210. NYU,DEPT CHEM,NEW YORK,NY 10003. NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. AMER HLTH FDN,VALHALLA,NY 10595. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,CTR COMPREHENS CANC,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,SCH PUBL HLTH,NEW YORK,NY 10032. OI RONAI, ZEEV/0000-0002-3859-0400 FU NCI NIH HHS [CA 02111, CA 2111-15, CA 42500] NR 28 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC PY 1992 VL 203 IS 2 BP 329 EP 335 DI 10.1016/0014-4827(92)90006-T PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA KD842 UT WOS:A1992KD84200006 PM 1459198 ER PT J AU ONO, M NAKAYAMA, Y PRINCLER, G GOPAS, J KUNG, H KUWANO, M AF ONO, M NAKAYAMA, Y PRINCLER, G GOPAS, J KUNG, H KUWANO, M TI POLYOMA MIDDLE T-ANTIGEN OR V-SRC DESENSITIZES HUMAN EPIDERMAL GROWTH-FACTOR RECEPTOR FUNCTION AND INTERFERENCE BY A MONENSIN-RESISTANT MUTATION IN MOUSE BALB/3T3 CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; PROTEIN KINASE-C; TYROSINE PHOSPHORYLATION; MALIGNANT TRANSFORMATION; CHEMICAL CARCINOGENS; SIGNAL TRANSDUCTION; TUMOR-ANTIGEN; EGF; FIBROBLASTS; PP60C-SRC C1 BEN GURION UNIV NEGEV,DEPT MICROBIOL & IMMUNOL,BEER SHEVA,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. RP ONO, M (reprint author), OITA MED UNIV,DEPT BIOCHEM,HASAMA,OITA 87955,JAPAN. NR 60 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC PY 1992 VL 203 IS 2 BP 456 EP 465 DI 10.1016/0014-4827(92)90021-Y PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA KD842 UT WOS:A1992KD84200021 PM 1459205 ER PT J AU SOLARY, E BERTRAND, R JENKINS, J POMMIER, Y AF SOLARY, E BERTRAND, R JENKINS, J POMMIER, Y TI RADIOLABELING OF DNA CAN INDUCE ITS FRAGMENTATION IN HL-60 HUMAN PROMYELOCYTIC LEUKEMIC-CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Note ID APOPTOSIS; DEATH; IRRADIATION; LINES C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,R5C27,BETHESDA,MD 20892. NR 21 TC 16 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC PY 1992 VL 203 IS 2 BP 495 EP 498 DI 10.1016/0014-4827(92)90027-6 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA KD842 UT WOS:A1992KD84200027 PM 1459209 ER PT J AU ORLIC, D BODINE, DM AF ORLIC, D BODINE, DM TI PLURIPOTENT HEMATOPOIETIC STEM-CELLS OF LOW AND HIGH-DENSITY CAN REPOPULATE W/W(V) MICE SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE HEMATOPOIETIC STEM CELLS; CFU-S; W/W(V) MICE ID COLONY-FORMING CELLS; RHODAMINE-123 FLUORESCENCE; CFU-S; MARROW; SPLEEN; MOUSE; SEPARATION; ASSAY AB We have studied several features of pluripotent hematopoietic stem cells (PHSC) and day-12 spleen colony-forming units (CFU-S12) in murine bone marrow. C57BL/6J marrow cell suspensions were separated by elutriation and fractions were obtained at flow rates (FR) of 2 5 ml/min, 29/30 ml/min, 35 ml/min, and with the rotor off. All four fractions contained PHSC that could repopulate W/W(v) mice, but significant numbers of CFU-S12 were found only in the three higher FR fractions. Cells in the FR29/30 fraction were shown to have almost three-fold more repopulating activity than fresh marrow in a competitive repopulation assay. The PHSC in fractions separated by elutriation were enriched by depleting cells expressing specific lineage markers with monoclonal antibodies and magnetic immunobeads. As few as 10(4) lineage negative (lin-) cells from FR35 or 10(5) lin-cells from FR25 conferred long-term multilineage repopulation in W/W(v) mice, as demonstrated by Southern blot analysis of DNA from recipient thymus and bone marrow. We conclude that PHSC are heterogeneous for cell size and density and that the highest concentration of PHSC resides in the subset of intermediate density present in the FR29/30 fraction. C1 NEW YORK MED COLL,DEPT CELL BIOL & ANAT,VALHALLA,NY 10595. RP ORLIC, D (reprint author), NHLBI,CLIN HEMATOL BRANCH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. NR 28 TC 21 Z9 22 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 1992 VL 20 IS 11 BP 1291 EP 1295 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA KB065 UT WOS:A1992KB06500008 PM 1493857 ER PT J AU NASH, TE MOWATT, MR AF NASH, TE MOWATT, MR TI IDENTIFICATION AND CHARACTERIZATION OF A GIARDIA-LAMBLIA GROUP-SPECIFIC GENE SO EXPERIMENTAL PARASITOLOGY LA English DT Article ID EXCRETORY-SECRETORY PRODUCTS; SURFACE-PROTEINS; SEQUENCE; LOCALIZATION; ANTIBODIES; NUCLEOTIDE; ANTIGEN; DISK RP NASH, TE (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 32 TC 39 Z9 41 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 1992 VL 75 IS 4 BP 369 EP 378 DI 10.1016/0014-4894(92)90250-E PG 10 WC Parasitology SC Parasitology GA KF085 UT WOS:A1992KF08500001 PM 1493870 ER PT J AU RAGHAVAN, N MAINA, CV FITZGERALD, PC TUAN, RS SLATKO, BE OTTESEN, EA NUTMAN, TB AF RAGHAVAN, N MAINA, CV FITZGERALD, PC TUAN, RS SLATKO, BE OTTESEN, EA NUTMAN, TB TI CHARACTERIZATION OF A MUSCLE-ASSOCIATED ANTIGEN FROM WUCHERERIA-BANCROFTI SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE NEMATA; FILARIOIDEA; WUCHERERIA-BANCROFTI; BRUGIA-MALAYI; BRUGIA-PAHANGI; ONCHOCERCA-VOLVULUS; LYMPHATIC FILARIASIS; MYOSIN-LIKE ANTIGEN ID HEAVY-CHAIN GENE; CAENORHABDITIS-ELEGANS; ONCHOCERCA-VOLVULUS; HUMAN FILARIASIS; BINDING PROTEIN; MYOSIN; LOCALIZATION; HYBRIDIZATION; CDNA; IGG C1 NEW ENGLAND BIOLABS INC,BEVERLY,MA 01915. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,DEPT ORTHOPED RES,PHILADELPHIA,PA 19107. RP RAGHAVAN, N (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 30 TC 6 Z9 6 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 1992 VL 75 IS 4 BP 379 EP 389 DI 10.1016/0014-4894(92)90251-5 PG 11 WC Parasitology SC Parasitology GA KF085 UT WOS:A1992KF08500002 PM 1283597 ER PT J AU WOLFFE, AP AF WOLFFE, AP TI NEW INSIGHTS INTO CHROMATIN FUNCTION IN TRANSCRIPTIONAL CONTROL SO FASEB JOURNAL LA English DT Article DE CHROMATIN; GENE REGULATION; HISTONE; TRANSCRIPTION; NUCLEOSOME ID POSITION-EFFECT VARIEGATION; TUMOR VIRUS PROMOTER; DROSOPHILA-MELANOGASTER; TOPOISOMERASE-II; RNA GENES; SACCHAROMYCES-CEREVISIAE; MITOTIC CHROMOSOMES; REPLICATING DNA; NUCLEOSOME; PROTEIN AB Transcription requires the recognition of numerous DNA sequences by diverse transcription factors, which together assemble large nucleoprotein complexes that tether RNA polymerase and facilitate the initiation of RNA synthesis. In vivo the assembly of these transcription complexes occurs in a nuclear environment where the template DNA is compacted more than 10(5)-fold through the assembly of chromatin. Our current knowledge of chromatin structure raises the major issues of the accessibility of DNA to both transcription factors and RNA polymerase and of the progression of RNA polymerase along the chromatin fiber. Novel genetic and biochemical approaches have established that specific chromatin structures have a major impact on the transcription process. Precise alterations in histone sequence, nucleosome structure, and folding of the chromatin fiber influence both the activation and repression of genes. These results offer substantial insight into the role of modulations in chromosome structure during vertebrate development. Transcription factors, histones, and the organization of DNA within the chromosome are intimately linked, and only when the correct framework is assembled can they function together to achieve correct genetic regulation. RP WOLFFE, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 77 TC 68 Z9 68 U1 0 U2 1 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 DEC PY 1992 VL 6 IS 15 BP 3354 EP 3361 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KD395 UT WOS:A1992KD39500006 PM 1464369 ER PT J AU YUAN, JH DIETER, MP BUCHER, JR JAMESON, CW AF YUAN, JH DIETER, MP BUCHER, JR JAMESON, CW TI TOXICOKINETICS OF CINNAMALDEHYDE IN F344 RATS SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID CINNAMIC ALDEHYDE; HIPPURIC ACID; CHROMATOGRAPHY; FRAGRANCE; TOXICITY; ALCOHOL; URINE AB The toxicokinetic profile of cinnamaldehyde (CNMA) was investigated in Fischer 344 rats. CNMA was found to be unstable in blood. After iv administration, a large fraction of CNMA was immediately oxidized to cinnamic acid. The biological half-life of CNMA after iv administration was found to be 1.7 hr. After administration by gavage of CNMA at 250 or 500 mg/kg body weight using com oil as vehicle, the maximum blood concentrations of CNMA were in the order of 1 mug/ml. These low blood concentrations were maintained over a 24-hr period after a dose of 500 mg/kg, which is relatively long considering the short (1.7 hr) biological half-life of CNMA. The estimated oral bioavailability of CNMA was less than 20% for both the 250 and 500 mg/kg doses. No CNMA was present in blood at any time in rats dosed with 50 mg CNMA/kg body weight. Only a small amount of the administered CNMA was excreted in rat urine as free cinnamic acid or beta-glucuronide-conjugated cinnamic acid. The majority of CNMA administered orally was excreted in urine as hippuric acid within 24 hr. The maximum excretion rate occurred at 8 hr after gavage. Hippuric acid recovered in 50-hr urine samples was found to be directly proportional to the oral dose of CNMA. RP YUAN, JH (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 21 TC 30 Z9 37 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD DEC PY 1992 VL 30 IS 12 BP 997 EP 1004 DI 10.1016/0278-6915(92)90109-X PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA KG676 UT WOS:A1992KG67600001 PM 1473801 ER PT J AU PIROZHKOV, SV WATSON, RR ESKELSON, CD AF PIROZHKOV, SV WATSON, RR ESKELSON, CD TI GAS-CHROMATOGRAPHIC DETECTION OF COCAINE AND COCAETHYLENE IN HAIR OF MICE CHRONICALLY INJECTED WITH COCAINE OR COCAETHYLENE AND FED ETHANOL SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article DE HAIR ANALYSIS; COCAINE; COCAETHYLENE; GAS CHROMATOGRAPHY ID METABOLITES AB GC and GC/MS analysis was used to detect cocaine and cocaethylene in hair extracts of mice injected with 20 mg/kg cocaine hydrochloride or an equivalent dose of cocaethylene fumarate twice daily for 3 weeks. Some mice were fed liquid Lieber-DeCarli diets containing ethanol (26% of total calories) and injected twice daily with the same doses of cocaine or cocaethylene or combination of cocaine and morphine (5 mg/kg). The average concentrations of cocaine in different experimental groups were in the range of 0.9 - 2.4 ng/mg of hair and for cocaethylene, 2.4 - 2.8 ng/mg of hair. There were no significant differences in hair concentrations of cocaine among groups receiving cocaine treatment, nor were there significant difference in cocaethylene concentration in hair in the two groups administered cocaethylene. In hair extracts of mice treated with cocaine and ethanol, levels of cocaethylene were below the limit of detection. C1 UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT FAMILY & COMMUNITY MED,NIAAA,ALCOHOL RES CTR,TUCSON,AZ 85724. MOSCOW MEDICOBIOL PROBLEMS ADDICT RES INST,MOSCOW 121921,RUSSIA. UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT SURG BIOL,NIAAA,ALCOHOL RES CTR,TUCSON,AZ 85724. NR 10 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD DEC PY 1992 VL 57 IS 2 BP 99 EP 107 DI 10.1016/0379-0738(92)90002-E PG 9 WC Medicine, Legal SC Legal Medicine GA KF788 UT WOS:A1992KF78800002 PM 1473811 ER PT J AU BOCKMAN, DE MERLINO, G AF BOCKMAN, DE MERLINO, G TI CYTOLOGICAL CHANGES IN THE PANCREAS OF TRANSGENIC MICE OVEREXPRESSING TRANSFORMING GROWTH-FACTOR ALPHA SO GASTROENTEROLOGY LA English DT Article ID TUBULAR COMPLEXES; NECROHEMORRHAGIC PANCREATITIS; TGF-ALPHA; EXPRESSION; CANCER; CELLS; RAT; REGENERATION; INDUCTION; CARCINOMA C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP BOCKMAN, DE (reprint author), MED COLL GEORGIA,DEPT CELLULAR BIOL & ANAT,AUGUSTA,GA 30912, USA. NR 31 TC 96 Z9 97 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1992 VL 103 IS 6 BP 1883 EP 1892 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KA026 UT WOS:A1992KA02600024 PM 1451981 ER PT J AU STANTON, BR PERKINS, AS TESSAROLLO, L SASSOON, DA PARADA, LF AF STANTON, BR PERKINS, AS TESSAROLLO, L SASSOON, DA PARADA, LF TI LOSS OF N-MYC FUNCTION RESULTS IN EMBRYONIC LETHALITY AND FAILURE OF THE EPITHELIAL COMPONENT OF THE EMBRYO TO DEVELOP SO GENES & DEVELOPMENT LA English DT Article DE N-MYC GENE; MOUSE EMBRYOGENESIS; POSTIMPLANTATION DEVELOPMENT ID DNA-BINDING; C-MYC; DIFFERENTIAL EXPRESSION; NEURO-BLASTOMA; STEM-CELLS; HOMOLOGOUS RECOMBINATION; HUMAN NEUROBLASTOMAS; NUCLEOTIDE-SEQUENCE; FAMILY GENES; MOUSE EMBRYO AB myc genes are thought to function in the processes of cellular proliferation and differentiation. To gain insight into the role of the N-myc gene during embryogenesis, we examined its expression in embryos during postimplantation development using RNA in situ hybridization. Tissue- and cell-specific patterns of expression unique to N-myc as compared with the related c-myc gene were observed. N-myc transcripts become progressively restricted to specific cell types, primarily to epithelial tissues including those of the developing nervous system and those in developing organs characterized by epithelio-mesenchymal interaction. In contrast, c-myc transcripts were confined to the mesenchymal compartments. These data suggest that c-myc and N-myc proteins may interact with different substrates in performing their function during embryogenesis and suggest further that there are linked regulatory mechanisms for normal expression in the embryo. We have mutated the N-myc locus via homologous recombination in embryonic stem (ES) cells and introduced the mutated allele into the mouse germ line. Live-born heterozygotes are under-represented but appear normal. Homozygous mutant embryos die prenatally at approximately 11.5 days of gestation. Histologic examination of homozygous mutant embryos indicates that several developing organs are affected. These include the central and peripheral nervous systems, mesonephros, lung, and gut. Thus, N-myc function is required during embryogenesis, and the pathology observed is consistent with the normal pattern of N-myc expression. Examination of c-myc expression in mutant embryos indicates the existence of coordinate regulation of myc genes during mouse embryogenesis. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MOLEC GENET ONCOGENESIS SECT,FREDERICK,MD 21702. RP PARADA, LF (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MOLEC EMBRYOL SECT,FREDERICK,MD 21702, USA. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101] NR 57 TC 256 Z9 264 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC PY 1992 VL 6 IS 12A BP 2235 EP 2247 DI 10.1101/gad.6.12a.2235 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA KB977 UT WOS:A1992KB97700001 PM 1459449 ER PT J AU PRICE, SR NIGHTINGALE, MS BOBAK, DA TSUCHIYA, M MOSS, J VAUGHAN, M AF PRICE, SR NIGHTINGALE, MS BOBAK, DA TSUCHIYA, M MOSS, J VAUGHAN, M TI CONSERVATION OF A 23-KDA HUMAN TRANSPLANTATION ANTIGEN IN MAMMALIAN-SPECIES SO GENOMICS LA English DT Article ID GENE C1 NHLBI,CELLULAR METAB LAB,BLDG 10,ROOM 5N307,BETHESDA,MD 20892. NR 10 TC 9 Z9 10 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 DEC PY 1992 VL 14 IS 4 BP 959 EP 964 DI 10.1016/S0888-7543(05)80117-X PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA KE785 UT WOS:A1992KE78500017 PM 1282492 ER PT J AU SMITH, RJH LEE, EC KIMBERLING, WJ DAIGER, SP PELIAS, MZ KEATS, BJB JAY, M BIRD, A REARDON, W GUEST, M AYYAGARI, R HEJTMANCIK, JF AF SMITH, RJH LEE, EC KIMBERLING, WJ DAIGER, SP PELIAS, MZ KEATS, BJB JAY, M BIRD, A REARDON, W GUEST, M AYYAGARI, R HEJTMANCIK, JF TI LOCALIZATION OF 2 GENES FOR USHER SYNDROME TYPE-I TO CHROMOSOME-11 SO GENOMICS LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; NEUROTROPHIC FACTOR; LINKAGE ANALYSIS; LOCUS; HETEROGENEITY; EXPRESSION; NEURONS; MOUSE C1 UNIV TEXAS,HLTH SCI CTR,DEPT GENET,HOUSTON,TX 77225. BOYS TOWN NATL RES HOSP,HOUSTON,TX. LOUISIANA STATE UNIV,MED CTR,DEPT BIOMETRY & GENET,NEW ORLEANS,LA 70112. INST OPHTHALMOL,LONDON WC1H 9QS,ENGLAND. MOORFIELDS EYE HOSP,LONDON WC1V 7AN,ENGLAND. INST CHILD HLTH,MOTHERCARE DEPT CHILD HLTH,LONDON WC1N 1EH,ENGLAND. SENSE,USHER SYNDROME PROJECT,LONDON,ENGLAND. NEI,BETHESDA,MD 20892. RP SMITH, RJH (reprint author), UNIV IOWA,DEPT OTOLARYNGOL HEAD & NECK SURG,MOLEC OTOLARYNGOL RES LABS,IOWA CITY,IA 52242, USA. FU NCRR NIH HHS [RR-05425]; NEI NIH HHS [EY07142, R01 EY007142] NR 41 TC 156 Z9 156 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 DEC PY 1992 VL 14 IS 4 BP 995 EP 1002 DI 10.1016/S0888-7543(05)80122-3 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA KE785 UT WOS:A1992KE78500022 PM 1478678 ER PT J AU SPURR, NK COX, S BRYANT, SP ATTWOOD, J ROBSON, EB SHIELDS, DC STEINBRUECK, T JENKINS, T MURRAY, JC KIDD, KK SUMMAR, ML TSIPOURAS, P RETIEF, AE KRUSE, TA BALE, AE VERGNAUD, G WEBER, JL MCBRIDE, OW DONISKELLER, H WHITE, RL AF SPURR, NK COX, S BRYANT, SP ATTWOOD, J ROBSON, EB SHIELDS, DC STEINBRUECK, T JENKINS, T MURRAY, JC KIDD, KK SUMMAR, ML TSIPOURAS, P RETIEF, AE KRUSE, TA BALE, AE VERGNAUD, G WEBER, JL MCBRIDE, OW DONISKELLER, H WHITE, RL TI THE CEPH CONSORTIUM LINKAGE MAP OF HUMAN CHROMOSOME-2 SO GENOMICS LA English DT Article ID SYNDROME TYPE-I; HUMAN GENOME; ASSOCIATION; MARKERS; LOCUS; DNA C1 UNIV LONDON UNIV COLL,MRC,HUMAN BIOCHEM GENET UNIT,GALTON LAB,LONDON NW1 2HE,ENGLAND. PRINCESS ANNE HOSP,DEPT CHILD HLTH,CRC GENET EPIDEMIOL RES GRP,SOUTHAMPTON SO9 4HA,ENGLAND. WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110. S AFRICAN INST MED RES,SCH PATHOL,DEPT HUMAN GENET,MRC,HUMAN ECOGENET RES UNIT,JOHANNESBURG 2000,SOUTH AFRICA. UNIV WITWATERSRAND,JOHANNESBURG 2001,SOUTH AFRICA. UNIV IOWA,DEPT PEDIAT,IOWA CITY,IA 52242. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. VANDERBILT UNIV,MED CTR,DEPT PEDIAT,NASHVILLE,TN 37232. UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT,MOLEC GENET LAB,FARMINGTON,CT 06032. UNIV STELLENBOSCH,STELLENBOSCH 7600,SOUTH AFRICA. AARHUS UNIV,BARTOLIN BYGNINGEN,INST HUMAN GENET,DK-8000 AARHUS,DENMARK. CTR ETUD BOUCHET,F-91710 VERT LE PETIT,FRANCE. MARSHFIELD MED RES FDN,MARSHFIELD,WI 54449. NCI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84132. UNIV LONDON UNIV COLL,DEPT GENET & BIOMETRY,GALTON LAB,LONDON NW1 2HE,ENGLAND. RP SPURR, NK (reprint author), IMPERIAL CANC RES FUND,HUMAN GENET RESOURCES UNIT,BLANCHE LANE,POTTERS BAR EN6 3LD,HERTS,ENGLAND. RI Vergnaud, Gilles/P-1304-2015 OI Vergnaud, Gilles/0000-0003-0913-194X FU NHGRI NIH HHS [HG-00248, HG-00469]; NIDCR NIH HHS [DE-08559] NR 25 TC 19 Z9 19 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 DEC PY 1992 VL 14 IS 4 BP 1055 EP 1063 DI 10.1016/S0888-7543(05)80129-6 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA KE785 UT WOS:A1992KE78500029 PM 1478647 ER PT J AU CHIN, H KRALL, M KIM, HL KOZAK, CA MOCK, B AF CHIN, H KRALL, M KIM, HL KOZAK, CA MOCK, B TI THE GENE FOR THE ALPHA-1-SUBUNIT OF THE SKELETAL-MUSCLE DIHYDROPYRIDINE-SENSITIVE CALCIUM-CHANNEL (CCHL1A3) MAPS TO MOUSE CHROMOSOME-1 SO GENOMICS LA English DT Note ID ALPHA-1 SUBUNIT; RECEPTOR; LOCUS; MICE C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NCI,GENET LAB,BETHESDA,MD 20892. RP CHIN, H (reprint author), NINCDS,MOLEC BIOL LAB,BLDG 36,ROOM 3D-02,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CB-71085] NR 15 TC 15 Z9 16 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 DEC PY 1992 VL 14 IS 4 BP 1089 EP 1091 DI 10.1016/S0888-7543(05)80134-X PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA KE785 UT WOS:A1992KE78500034 PM 1335956 ER PT J AU VANDENBERGH, DJ PERSICO, AM HAWKINS, AL GRIFFIN, CA LI, X JABS, EW UHL, GR AF VANDENBERGH, DJ PERSICO, AM HAWKINS, AL GRIFFIN, CA LI, X JABS, EW UHL, GR TI HUMAN DOPAMINE TRANSPORTER GENE (DAT1) MAPS TO CHROMOSOME-5P15.3 AND DISPLAYS A VNTR SO GENOMICS LA English DT Note ID INSITU HYBRIDIZATION; PARKINSONS-DISEASE; INHERITANCE; ALCOHOLISM; RECEPTORS; COCAINE C1 NIDA,ADDICT RES CTR,MOLEC NEUROBIOL LAB,POB 5180,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21205. OI Jabs, Ethylin/0000-0001-8983-5466 FU NIDCR NIH HHS [DE10180]; NIGMS NIH HHS [5P01 GM1015-02] NR 15 TC 485 Z9 505 U1 4 U2 11 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 DEC PY 1992 VL 14 IS 4 BP 1104 EP 1106 DI 10.1016/S0888-7543(05)80138-7 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA KE785 UT WOS:A1992KE78500038 PM 1478653 ER PT J AU CHEN, HM PHILLIPS, HA CALLEN, DF KIM, RY WISTOW, GJ ANTONARAKIS, SE AF CHEN, HM PHILLIPS, HA CALLEN, DF KIM, RY WISTOW, GJ ANTONARAKIS, SE TI LOCALIZATION OF THE HUMAN GENE FOR MU-CRYSTALLIN TO CHROMOSOME-16P SO GENOMICS LA English DT Note C1 JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21287. ADELAIDE CHILDRENS HOSP INC,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA 5006,AUSTRALIA. NEI,MOLEC STRUCT & FUNCT SECT,BETHESDA,MD 20892. RI Callen, David/G-1975-2012; Antonarakis, Stylianos/N-8866-2014; OI Antonarakis, Stylianos/0000-0001-8907-5823; Callen, David/0000-0002-6189-9991 FU NHGRI NIH HHS [HG00373] NR 5 TC 9 Z9 9 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 DEC PY 1992 VL 14 IS 4 BP 1115 EP 1116 DI 10.1016/S0888-7543(05)80143-0 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA KE785 UT WOS:A1992KE78500043 PM 1478656 ER PT J AU SCHNELLE, JF SIMMONS, SF ORY, MG AF SCHNELLE, JF SIMMONS, SF ORY, MG TI RISK-FACTORS THAT PREDICT STAFF FAILURE TO RELEASE NURSING-HOME RESIDENTS FROM RESTRAINTS SO GERONTOLOGIST LA English DT Article DE AGGRESSION; NEGLECT; STAFF MANAGEMENT AB This study identifies resident characteristics related to nursing staff failure to provide consistent release from physical restraints as required by regulation. The lengths of intervals during which residents were restrained were measured and correlated with the staff's perception of degree of care burden and resident behavioral characteristics in order to identify risk factors related to the absence of consistent release. Staff perceptions of residents' verbal aggressiveness (multiple R = -.30, p < .01), physical aggressiveness (multiple R = -.25, p < .03) and unpleasantness (multiple R = -.25, p < .03) are the three characteristics most predictive of the length of time residents continuously remain restrained. C1 NIA, BETHESDA, MD 20892 USA. RP SCHNELLE, JF (reprint author), UNIV CALIF LOS ANGELES, SCH MED, BORUN CTR GERONTOL RES, 10833 LE CONTE AVE, CHS 32-144, LOS ANGELES, CA 90024 USA. NR 8 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD DEC PY 1992 VL 32 IS 6 BP 767 EP 770 PG 4 WC Gerontology SC Geriatrics & Gerontology GA KB091 UT WOS:A1992KB09100008 PM 1478495 ER PT J AU BROWN, DR MILBURN, NG GARY, LE AF BROWN, DR MILBURN, NG GARY, LE TI SYMPTOMS OF DEPRESSION AMONG OLDER AFRICAN-AMERICANS - AN ANALYSIS OF GENDER DIFFERENCES SO GERONTOLOGIST LA English DT Article DE STRESSFUL LIFE EVENTS; SOCIAL ROLES; BLACK ELDERLY ID SEX-DIFFERENCES; MENTAL-HEALTH; LIFE EVENTS; ROLES; EPIDEMIOLOGY; COMMUNITIES; PREVALENCE; DISTRESS; ADULTS AB Using data from a community-based sample of African-Americans, this study investigated the association between gender and depressive symptoms among 148 African-Americans who are 65 years of age and older. Findings indicated no gender difference in overall level of depressive symptomatology. Further analyses suggest that the lack of a gender difference in depressive symptoms was attributable to similarities in risk factors related to stressful life events and the social roles associated with employment and childrearing. C1 HOFSTRA UNIV,HEMPSTEAD,NY 11550. VIRGINIA COMMONWEALTH UNIV,SCH SOCIAL WORK,RICHMOND,VA 23284. RP BROWN, DR (reprint author), NIH,OD,DEP,BLDG 31,5B35,BETHESDA,MD 20892, USA. FU NIMH NIH HHS [85 RO1 MH388386] NR 33 TC 18 Z9 18 U1 3 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD DEC PY 1992 VL 32 IS 6 BP 789 EP 795 PG 7 WC Gerontology SC Geriatrics & Gerontology GA KB091 UT WOS:A1992KB09100011 PM 1478498 ER PT J AU EANES, ED HAILER, AW MIDURA, RJ HASCALL, VC AF EANES, ED HAILER, AW MIDURA, RJ HASCALL, VC TI PROTEOGLYCAN INHIBITION OF CALCIUM-PHOSPHATE PRECIPITATION IN LIPOSOMAL SUSPENSIONS SO GLYCOBIOLOGY LA English DT Article DE CALCIFICATION; CALCIUM PHOSPHATES; LIPOSOMES; MINERALIZATION; PROTEOGLYCANS ID HYDROXYAPATITE FORMATION; CARTILAGE PROTEOGLYCANS; RAT CHONDROSARCOMA; CALCIFICATION; INVITRO; GROWTH; QUANTITIES; SULFATE AB The major proteoglycan in cartilage (aggrecan) is a complex macromolecule with numerous chondroitin sulphate, keratan sulphate, and oligosaccharide substituents. It has been proposed that this macromolecule has an important role in regulating mineralization in this tissue, a process which is initiated by the deposition of apatite in matrix vesicles. We have used a liposome-centred endogenous precipitation method as a model for matrix vesicle mineralization to study the effect of the rat chondrosarcoma aggrecan and its chondroitin sulphate and core protein components on apatite formation from solution. Precipitation was initiated by encapsulating buffered (Ph 7.4) 50 mmol/l KH2PO4 solutions in the aqueous centres of 7:2:1 phosphatidylcholine:dicetylphosphate:cholesterol liposomes, adding 2.25-2.65 mmol/l Ca2+ and 1.5 mmol/l total inorganic phosphate (PO4) to the suspending medium (Ph 7.4, 22-degrees-C), then making the intervening lipid membranes permeable to the Ca2+ ions with the calcium ionophore X-537A. Aggrecan (0.5%) in the suspending medium had no effect on intraliposomal precipitation, but severely reduced (approximately 70% reduction at 24 h) its subsequent spread into the medium. The chondroitin sulphate and core protein were similarly inhibitory. The degree to which aggrecan and its constituent parts inhibited precipitation correlated with their capacity to bind Ca2+ ions. These findings suggest that functional groups in aggrecan blocked apatite growth by linking via Ca2+ bridges to growth sites on the crystal surfaces. Similar Ca-mediated interactions may well have a critical regulatory role in cartilage mineralization. RP EANES, ED (reprint author), NATL INST STAND & TECHNOL,NIDR,RES ASSOCIATE PROGRAM,BLDG 224,ROOM A143,GAITHERSBURG,MD 20899, USA. NR 39 TC 22 Z9 22 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD DEC PY 1992 VL 2 IS 6 BP 571 EP 578 DI 10.1093/glycob/2.6.571 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KD042 UT WOS:A1992KD04200011 PM 1472764 ER PT J AU HSIA, CC EVARTS, RP NAKATSUKASA, H MARSDEN, ER THORGEIRSSON, SS AF HSIA, CC EVARTS, RP NAKATSUKASA, H MARSDEN, ER THORGEIRSSON, SS TI OCCURRENCE OF OVAL-TYPE CELLS IN HEPATITIS-B VIRUS-ASSOCIATED HUMAN HEPATOCARCINOGENESIS SO HEPATOLOGY LA English DT Article ID PROLIFERATING EPITHELIAL-CELLS; ALPHA-FETOPROTEIN; HEPATOCELLULAR-CARCINOMA; RAT-LIVER; CHEMICAL HEPATOCARCINOGENESIS; PHENOTYPIC CHARACTERIZATION; NODULAR TRANSFORMATION; ANTIGENIC EXPRESSION; VIRAL-HEPATITIS; FETAL LIVER AB Proliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and alpha-fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus-positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross-reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in alpha-fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of alpha-fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma. C1 NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892. NR 29 TC 166 Z9 174 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1992 VL 16 IS 6 BP 1327 EP 1333 DI 10.1002/hep.1840160604 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KB346 UT WOS:A1992KB34600003 PM 1280243 ER PT J AU GRAYSON, NA BOWEN, WD RICE, KC AF GRAYSON, NA BOWEN, WD RICE, KC TI CHIRAL, POTENTIALLY IRREVERSIBLE LIGANDS FOR THE SIGMA RECEPTOR BASED ON THE STRUCTURE OF 3-(3-HYDROXYPHENYL)-N-PROPYLPIPERIDINE (3-PPP) SO HETEROCYCLES LA English DT Article ID CENTRAL DOPAMINE; ANTIPSYCHOTIC-DRUGS; OPIATE RECEPTORS; 3-PHENYLPIPERIDINES; AFFINITY; ANALOGS; RAT AB (+)-3-PPP is an optically active, highly potent and selective ligand for sigma receptors. The resolved enantiomeric pairs of potential irreversible sigma ligands (5a,b) and (9a,b) were designed and synthesized based on the structure of 3-PPP. An improved method of resolution was developed for the common intermediate (2a,b). RP GRAYSON, NA (reprint author), NIDDK,MED CHEM INST,BLDG 8,RM B1-22,BETHESDA,MD 20892, USA. NR 24 TC 13 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD DEC 1 PY 1992 VL 34 IS 12 BP 2281 EP 2292 PG 12 WC Chemistry, Organic SC Chemistry GA KE054 UT WOS:A1992KE05400009 ER PT J AU SERRA, M MORINI, MC SCOTLANDI, K FISHER, LW ZINI, N COLOMBO, MP CAMPANACCI, M MARALDI, NM OLIVARI, S BALDINI, N AF SERRA, M MORINI, MC SCOTLANDI, K FISHER, LW ZINI, N COLOMBO, MP CAMPANACCI, M MARALDI, NM OLIVARI, S BALDINI, N TI EVALUATION OF OSTEONECTIN AS A DIAGNOSTIC MARKER OF OSTEOGENIC BONE-TUMORS SO HUMAN PATHOLOGY LA English DT Article DE OSTEONECTIN SECRETED PROTEIN ACIDIC AND RICH IN CYSTEINE; BONE TUMORS; IMMUNOHISTOCHEMISTRY; ELECTRON MICROSCOPY; MOLECULAR BIOLOGY ID BASEMENT-MEMBRANE TUMOR; PROTEIN BM-40; CELLS; ANTIBODIES; EXPRESSION; COLLAGEN; SPARC C1 IST ORTOPED RIZZOLI,RIC ONCOL LAB,VIA BARBIANO 1-10,I-40136 BOLOGNA,ITALY. IST ORTOPED RIZZOLI,CNR,IST CITOMORFOL NORMALE & PATOL,BOLOGNA,ITALY. NIH,BONE RES BRANCH,BETHESDA,MD 20892. IST NAZL TUMORI,I-20133 MILAN,ITALY. RP BALDINI, N (reprint author), IST ORTOPED RIZZOLI,RIC ONCOL LAB,VIA BARBIANO 1-10,I-40136 BOLOGNA,ITALY. RI Baldini, Nicola/J-4806-2016; Serra, Massimo/J-4878-2016; OI Baldini, Nicola/0000-0003-2228-3833; Serra, Massimo/0000-0003-0742-1177; Colombo, Mario Paolo/0000-0003-0042-7955 NR 20 TC 27 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 1992 VL 23 IS 12 BP 1326 EP 1331 DI 10.1016/0046-8177(92)90050-D PG 6 WC Pathology SC Pathology GA KC912 UT WOS:A1992KC91200003 PM 1468768 ER PT J AU CAMPO, E MERINO, MJ LIOTTA, L NEUMANN, R STETLERSTEVENSON, W AF CAMPO, E MERINO, MJ LIOTTA, L NEUMANN, R STETLERSTEVENSON, W TI DISTRIBUTION OF THE 72-KD TYPE-IV COLLAGENASE IN NONNEOPLASTIC AND NEOPLASTIC THYROID-TISSUE SO HUMAN PATHOLOGY LA English DT Article DE TYPE-IV COLLAGENASE; METALLOPROTEINASES; THYROID; TUMOR PROGRESSION; REMODELING; IMMUNOHISTOCHEMISTRY ID BASEMENT-MEMBRANE COLLAGEN; BRONCHIAL EPITHELIAL-CELLS; TUMOR INVASION; INTERSTITIAL COLLAGENASE; EXTRACELLULAR-MATRIX; HA-RAS; EXPRESSION; INHIBITOR; METASTASES; LAMININ C1 NCI,PATHOL LAB,BLDG 10,ROOM 2N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,DEPT NUCL MED,BETHESDA,MD 20892. RP MERINO, MJ (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Campo, elias/0000-0001-9850-9793 NR 44 TC 112 Z9 124 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 1992 VL 23 IS 12 BP 1395 EP 1401 DI 10.1016/0046-8177(92)90060-G PG 7 WC Pathology SC Pathology GA KC912 UT WOS:A1992KC91200013 PM 1468777 ER PT J AU HASLOV, K FOMSGAARD, A TAKAYAMA, K FOMSGAARD, JS IBSEN, P FAUNTLEROY, MB STASHAK, PW TAYLOR, CE BAKER, PJ AF HASLOV, K FOMSGAARD, A TAKAYAMA, K FOMSGAARD, JS IBSEN, P FAUNTLEROY, MB STASHAK, PW TAYLOR, CE BAKER, PJ TI IMMUNOSUPPRESSIVE EFFECTS INDUCED BY THE POLYSACCHARIDE MOIETY OF SOME BACTERIAL LIPOPOLYSACCHARIDES SO IMMUNOBIOLOGY LA English DT Article ID III PNEUMOCOCCAL POLYSACCHARIDE; T-CELL ACTIVITY; MONOPHOSPHORYL LIPID-A; BORDETELLA-PERTUSSIS ENDOTOXIN; ANTIBODY-RESPONSE; CYSTIC-FIBROSIS; COMPARATIVE IMMUNOCHEMISTRY; POLYACRYLAMIDE GELS; B-CELLS; SUPPRESSOR AB The immunomodulatory properties of several lipopolysaccharides (LPS) derived from clinical isolates of Pseudomonas aeruginosa, Branhamella catarrhalis, and Bordetella pertussis were evaluated for their capacity to influence the magnitude of the antibody response to type III pneumococcal polysaccharide (SSS-III), which is known to be regulated by suppressor and amplifier T cells (Ts and Ta, respectively). The administration of LPS, two days after immunization resulted in a significant increase in the.antibody response. Such enhancement may be due mainly to the ability of the lipid A moiety of LPS to abolish the negative effects of activated Ts, thereby enabling Ta function to be more fully expressed; however, B cell mitogenicity of the LPS molecule also may be involved. By contrast, treatment with LPS at the time of immunization with SSS-III induces significant suppression of the SSS-III-specific antibody response; such suppression is not induced by LPS or lipid A derived from Escherichia coli and Salmonella minnesota, and is independent of the capacity of LPS to activate B cells polyclonally, an activity by attributed to the lipid A fraction of LPS. Studies conducted with the LPS of P. aeruginosa indicated that the suppression induced is T cell dependent and mediated by the polysaccharide (PS) fraction of LPS; it appears to be due - at least in part - to the capacity of PS to expand or increase the size of the precursor pool of Ts, activated in response to SSS-III. The significance of these findings to the pathogenesis of certain gram-negative infections is discussed. C1 NIAID,IMMUNOGENET LAB,TWINBROOK II RES FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852. STATENS SERUM INST,DEPT VACCINE,DK-2300 COPENHAGEN,DENMARK. RIGSHOSP,DEPT CLIN MICROBIOL,DK-2100 COPENHAGEN,DENMARK. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL LAB,MADISON,WI 53705. NR 58 TC 9 Z9 9 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD DEC PY 1992 VL 186 IS 5 BP 378 EP 393 PG 16 WC Immunology SC Immunology GA KE556 UT WOS:A1992KE55600004 PM 1286878 ER PT J AU CARR, DJJ MAYO, S WOOLLEY, TW DECOSTA, BR AF CARR, DJJ MAYO, S WOOLLEY, TW DECOSTA, BR TI IMMUNOREGULATORY PROPERTIES OF (+)-PENTAZOCINE AND SIGMA-LIGANDS SO IMMUNOLOGY LA English DT Article ID KILLER-CELL-ACTIVITY; H-3 (+)-PENTAZOCINE; OPIOID RECEPTORS; BINDING-SITES; IMMUNE-SYSTEM; CYCLIC-AMP; LYMPHOCYTES; RAT AB (+)-Pentazocine, phencyclidine, and other sigma ligands including 1,3-di-(o)-tolylguanidine (DTG), (+)-1-propyl-3-(3-hydroxyphenyl) piperidine [(+)-PPP] and haloperidol were investigated for their potential immunoregulatory properties. High concentrations (10(-5) M) of DTG and haloperidol were found to suppress in vitro murine splenocyte natural killer activity while equivalent concentrations of (+)-pentazocine, (-)-pentazocine and (+)-PPP were without effect. In a reciprocal fashion, lower doses (10(-9) M) of DTG enhanced natural killer activity. Sigma ligands were also found to affect in vitro polyclonal immunoglobulin production following mitogen stimulation. Specifically, high concentrations (10(-6) M) of haloperidol significantly (P < 0.001) suppressed pokeweed mitogen (PWM)-stimulated IgG and IgM production, yet enhanced lipopolysaccharide (LPS)-stimulated IgM production by murine splenocytes. Lower concentrations (10(-8) to 10(-10) M) enhanced (two- to fourfold) PWM-induced IgM production and LPS-stimulated IgG and IgM production. At high concentrations (10(-6)) , (+)-pentazocine suppressed (P < 0.01) LPS-induced polyclonal IgG and IgM but enhanced (P < 0.01) PWM-induced IgM production. Both DTG and (-)-pentazocine (10(-8) to 10(-10) M) significantly augmented (two- to threefold) LPS-stimulated murine splenocyte production of polyclonal IgM. Intracellularly, (-)-pentazocine (10(-9) M), haloperidol (10(-7) M), DTG (10(-7) M) and (+)-PPP (10(-5) to 10(-9) M) enhanced forskolin (10(-6) M)-induced cAMP production in splenic lymphocytes while (+)-pentazocine was without effect. Collectively, the data suggest functional and biologically relevant sigma receptors on cells of the immune system. C1 UNIV ALABAMA,DEPT BIOSTAT,BIRMINGHAM,AL 35294. NIDDK,MED CHEM LAB,BETHESDA,MD. LOUISIANA STATE UNIV,MED CTR,CTR DRUG ABUSE,NEW ORLEANS,LA 70112. RP CARR, DJJ (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT MICROBIOL IMMUNOL & PARASITOL,1901 PERDIDO ST,NEW ORLEANS,LA 70112, USA. NR 21 TC 28 Z9 29 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 1992 VL 77 IS 4 BP 527 EP 531 PG 5 WC Immunology SC Immunology GA KB173 UT WOS:A1992KB17300010 PM 1493925 ER PT J AU CORSINI, E DYKSTRA, C CRAIG, WA TIDWELL, RR ROSENTHAL, GJ AF CORSINI, E DYKSTRA, C CRAIG, WA TIDWELL, RR ROSENTHAL, GJ TI PNEUMOCYSTIS-CARINII INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA BY ALVEOLAR MACROPHAGES - MODULATION BY PENTAMIDINE ISETHIONATE SO IMMUNOLOGY LETTERS LA English DT Article DE ALVEOLAR MACROPHAGES; PNEUMOCYSTIS-CARINII; TUMOR NECROSIS FACTOR-ALPHA; GAMMA-INTERFERON; PENTAMIDINE; AIDS ID AIDS PATIENTS; PNEUMONIA; INTERLEUKIN-1; MICE AB Pneumocystis carinii, and the inflammatory response it provokes, together contribute to irreversible lung damage in immunocompromised patients. P. carinii cysts were found to be capable of inducing tumor necrosis factor-alpha (TNF) release from alveolar macrophages in a concentration-dependent manner. At physiologically achievable concentrations, pentamidine isethionate (pentamidine) substantially reduces such production. Pretreatment of alveolar macrophages (AMO) with interferon-gamma (IFN-gamma) synergizes with P. carinii to produce increased levels of TNF, a condition which pentamidine was also able to antagonize. Pentamidine treatment did not interfere with the phagocytic ability of AMO. Considering clinical reduction of TNF could lessen P. carinii pneumonia (PCP) induced inflammation, the efficacy of pentamidine in the treatment of PCP may be partially associated with its ability to inhibit the release of inflammatory mediators such as TNF. C1 NIEHS,DIV TOXICOL RES & TESTING,IMMUNOTOXICOL SECT,POB 12233,RES TRIANGLE PK,NC 27709. INST PHARMACOL SCI,MILAN,ITALY. UNIV N CAROLINA,SCH MED,DEPT PATHOL,CHAPEL HILL,NC 27514. RI Corsini, Emanuela/B-5602-2011 NR 29 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD DEC PY 1992 VL 34 IS 3 BP 303 EP 308 DI 10.1016/0165-2478(92)90228-G PG 6 WC Immunology SC Immunology GA KE719 UT WOS:A1992KE71900019 PM 1487315 ER PT J AU PINCUS, SH ROSA, PA SPANGRUDE, GJ HEINEMANN, JA AF PINCUS, SH ROSA, PA SPANGRUDE, GJ HEINEMANN, JA TI THE INTERPLAY OF MICROBES AND THEIR HOSTS SO IMMUNOLOGY TODAY LA English DT Article ID DNA; GENES AB Microbes and their hosts exert considerable evolutionary pressure on one another. This brief report of a recent meeting* describes the strategies and tactics, and highlights some of the key molecules involved in the complex host-parasite relationship. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. RP PINCUS, SH (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 20 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD DEC PY 1992 VL 13 IS 12 BP 471 EP 473 DI 10.1016/0167-5699(92)90019-4 PG 3 WC Immunology SC Immunology GA KC285 UT WOS:A1992KC28500002 PM 1463577 ER PT J AU GAYDOS, CA QUINN, TC BOBO, LD EIDEN, JJ AF GAYDOS, CA QUINN, TC BOBO, LD EIDEN, JJ TI SIMILARITY OF CHLAMYDIA-PNEUMONIAE STRAINS IN THE VARIABLE DOMAIN-IV REGION OF THE MAJOR OUTER-MEMBRANE PROTEIN GENE SO INFECTION AND IMMUNITY LA English DT Note ID RESTRICTION ENDONUCLEASE ANALYSIS; NUCLEOTIDE-SEQUENCE; PSITTACI STRAINS; HL CELLS; TRACHOMATIS; TWAR; INFECTION; DISEASE AB DNA was amplified by polymerase chain reaction from the gene encoding the major outer membrane protein (MOMP) of Chlamydia pneumoniae in order to examine the relatedness of strains isolated from diverse geographical regions. Primers for this reaction were chosen to span a 207-bp region comparable to that of the fourth variable segment of the MOMP gene of Chlamydia trachomatis. Among C. trachomatis, sequence heterogeneity is characteristic within variable sequence domain IV (VDIV) and correlates with serovar type. In contrast, sequence analysis of polymerase chain reaction products from 13 C. pneumoniae isolates indicated that all tested strains were identical in this segment of the MOMP gene. The predicted amino acid sequences from the C. pneumoniae VDIV gene products shared only 13.3 to 30% homology with published VDIV regions from serovars of C. trachomatis. Homology of these VDIV amino acid sequences with sequences from strains of C. psittaci ranged from 45.7 to 60%. The sequence conservation of the VDIV region of the MOMP gene indicates that Cd. pneumoniae strains may be more genetically homogeneous than C. trachomatis or Chlamydia psittaci strains. Future investigations of antigenic diversity among C. pneumoniae strains should be aimed at the evaluation of variation in other regions of the C. pneumoniae genome. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP GAYDOS, CA (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21205, USA. RI Gaydos, Charlotte/E-9937-2010 NR 41 TC 35 Z9 36 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 DEC PY 1992 VL 60 IS 12 BP 5319 EP 5323 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JZ989 UT WOS:A1992JZ98900051 PM 1339411 ER PT J AU PANZA, JA QUYYUMI, AA AF PANZA, JA QUYYUMI, AA TI CIRCADIAN VARIATION AND DYNAMIC CORONARY VASOCONSTRICTION SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SUDDEN CARDIAC DEATH; UNSTABLE ANGINA-PECTORIS; ISCHEMIC HEART-DISEASE; ESSENTIAL-HYPERTENSION; MORNING INCREASE; DIURNAL-VARIATION; ARTERY DISEASE; ADRENERGIC VASOCONSTRICTION; CARDIOVASCULAR-DISEASE C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RP PANZA, JA (reprint author), NIH,DIV CARDIOL,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 70 TC 2 Z9 2 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD WIN PY 1992 VL 30 IS 1 BP 115 EP 129 PG 15 WC Anesthesiology SC Anesthesiology GA HN194 UT WOS:A1992HN19400010 PM 1577535 ER PT J AU HERRERO, R BRINTON, LA REEVES, WC BRENES, MM DEBRITTON, RC GAITAN, E TENORIO, F AF HERRERO, R BRINTON, LA REEVES, WC BRENES, MM DEBRITTON, RC GAITAN, E TENORIO, F TI SCREENING FOR CERVICAL-CANCER IN LATIN-AMERICA - A CASE-CONTROL STUDY SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID SMEAR HISTORIES; PAP SMEAR; RISK; POPULATION; CYTOLOGY AB The beneficial effect of cervical cytology in reducing the incidence of invasive cervical cancer is well accepted, but many issues regarding specific patterns of screening remain to be resolved, and preventive programmes need to be adapted to regional characteristics. In a case-control study conducted in Latin America, we investigated cytological screening histories of 759 cases of invasive cervical cancer and 1430 controls, with participation rates of 99% and 96%, respectively. Fifty per cent of the cases and 29% of the controls reported never having been screened. Screening was less common among older, less educated and less parous women; non-users of oral contraceptives and women without histories of venereal diseases. There was also evidence that older women and those with multiple partners had longer intervals between examinations. The relative risk (RR) associated with no prior screening was approximately 3 and was not modified by other risk factors. Women reporting a Pap smear within 24-47 months before interview had the same RR as those examined within 12-23 months. Women tested longer ago had higher risks, but still much lower than women never examined. There was evidence that one examination is associated with less reduction in risk than two, regardless of the interval since last Pap smear. Screening appeared to reduce risk of both squamous cell carcinomas and adenocarcinomas. As expected, cases presenting at advanced stages were less likely to have been screened and reported longer intervals since their last examination. These results support the need to concentrate limited resources in the groups that need screening most, mainly older and less educated women who have never been screened. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUTIVE PLAZA N,ROOM 443,BETHESDA,MD 20892. UNIDAD NACL CANCEROL,SAN JOSE,COSTA RICA. GORGAS MEM LAB,PANAMA CITY,PANAMA. INST ONCOL NACL,PANAMA CITY,PANAMA. INST NACL CANCEROL,DIV EPIDEMIOL,BOGOTA,COLOMBIA. INST MEXICANO SEGURO SOCIAL,HOSP ONCOL NACL,MEXICO CITY 7,DF,MEXICO. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [N01-CP-41026, R01-CA-42042] NR 27 TC 53 Z9 60 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1992 VL 21 IS 6 BP 1050 EP 1056 DI 10.1093/ije/21.6.1050 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KF280 UT WOS:A1992KF28000002 PM 1336485 ER PT J AU ALBINI, A REPETTO, L CARLONE, S BENELLI, R SORIA, M MONACO, L GENDELMAN, R DEFILIPPI, P BUSSOLINO, F PARRAVICINI, C AF ALBINI, A REPETTO, L CARLONE, S BENELLI, R SORIA, M MONACO, L GENDELMAN, R DEFILIPPI, P BUSSOLINO, F PARRAVICINI, C TI CHARACTERIZATION OF KAPOSIS SARCOMA-DERIVED CELL-CULTURES FROM AN EPIDEMIC AND A CLASSIC CASE SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE KAPOSIS SARCOMA; AIDS; TISSUE CULTURE ID HUMAN-ENDOTHELIAL-CELLS; LONG-TERM CULTURE; GROWTH-FACTORS; TUMOR-CELLS; INVITRO; EXPRESSION; INVASIVENESS; FIBROBLASTS; RAS AB Cells derived from skin biopsies from two Kaposi's sarcoma patients, an elderly female with a sporadic non-AIDS form, and an AIDS-affected homosexual male, were established in culture. The classic patient had a few small lesions, while the epidemic case presented-large, disseminated, cutaneous and oral mucosa lesions. The cells obtained from both patients, termed IST-KS2 and AIDS-IST-KS3 respectively, had the characteristic spindle shape reported for Kaposi's sarcoma-derived cells. By immunocytochemistry they were both found to express the smooth muscle specific isoform of alpha actin. The KS cells expressed the fibroblastic antigen TE-7, which is not expressed in endothelial cells. Furthermore both KS cultures were negative for the endothelium associated markers Factor VIII, EN4 and PAL-E. They were also negative for the leukocyte antigen CD45, but were positive for vimentin. Immunocytochemistry studies were therefore suggestive of a primitive mesenchymal cell. When the KS-derived cells were grown on a gel of reconstituted basement membrane, both cultures formed large branching colonies characteristic of malignant cells of mesenchymal origin. No differences were observed between HIV-related and the sporadic KS-derived cultures studied. Fibroblasts and smooth muscle cells did not form branching colonies, while endothelial cells on matrigel differentiated forming tube-like structures. Supernatants from both sporadic and AIDS-related KS cell cultures had similar effects on endothelial cell growth in vitro and were also found to stimulate chemotaxis and chemoinvasion of normal vascular endothelial cells in the Boyden chamber assay, showing angiogenic potential in vitro. Our results demonstrate that long term cultures of spindle shaped cells derived from either HIV-associated and classic KS show the same histocytochemical phenotype, have invasiveness in matrigel similar to that of malignant sarcomas, and share in vitro angiogenic properties. Therefore, factors from the host are likely to be responsible for the divergent clinical picture of the classic and epidemic Kaposi's patients studied here. C1 IST SCI SAN RAFFAELE,DIPARTIMENTO BIOTECHNOL,I-20133 MILAN,ITALY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. DIPARTIMENTO GENET BIOL & CHIM MED,I-10126 TURIN,ITALY. OSPED L SACCO,I-20157 MILAN,ITALY. RP ALBINI, A (reprint author), IST,IST NAZL RIC CANC,DEPT CHEM CARCINOGENESIS,VIALE BENEDETTO XV 10,I-16132 GENOA,ITALY. NR 34 TC 35 Z9 35 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 1992 VL 1 IS 7 BP 723 EP 730 PG 8 WC Oncology SC Oncology GA JZ109 UT WOS:A1992JZ10900001 PM 21584607 ER PT J AU SEN, HA BERKOWITZ, BA ANDO, N DEJUAN, E AF SEN, HA BERKOWITZ, BA ANDO, N DEJUAN, E TI INVIVO IMAGING OF BREAKDOWN OF THE INNER AND OUTER BLOOD-RETINAL BARRIERS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE BLOOD-RETINAL BARRIER; GD-DTPA; INVIVO; MRI; PERMEABILITY ID INJECTION AB Real-time contrast-enhanced magnetic resonance imaging (MRI) was used to distinguish between experimentally induced breakdown of the vascular (inner) and retinal pigment epithelial (RPE; outer) blood-retinal barrier (BRB) in vivo. Pigmented rabbits were treated with intravenous sodium iodate 30 mg/kg, (a specific RPE cell poison), intravitreal N-ethylcarboxamidoadenosine (NECA) 10(-3) mol/l (which specifically disrupts the vascular BRB), or retinal diode laser photocoagulation. Coronal T1-weighted proton images were acquired in a timed sequence after intravenous injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). Images were analyzed to localize leakage of Gd-DTPA and determine the permeability surface area product normalized per unit area (PS'). The pattern of enhancement observed in eyes treated with sodium iodate differed clearly from that in eyes treated with NECA. PS' values were significantly higher in eyes treated with sodium iodate than with NECA. Simultaneous leakage from the outer and inner BRB in eyes treated with dense retinal laser photocoagulation could be localized and quantitated independently. C1 DUKE UNIV,CTR EYE,DURHAM,NC 27706. NIEHS,RES TRIANGLE PK,NC 27709. RP DEJUAN, E (reprint author), WILMER OPHTHALMOL INST,600 N WOLFE ST,MAUMENEE 721,BALTIMORE,MD 21287, USA. FU NEI NIH HHS [R01 EY07576] NR 22 TC 31 Z9 31 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 DEC PY 1992 VL 33 IS 13 BP 3507 EP 3512 PG 6 WC Ophthalmology SC Ophthalmology GA KC415 UT WOS:A1992KC41500005 PM 1464497 ER PT J AU LEBIHAN, D AF LEBIHAN, D TI THEORETICAL PRINCIPLES OF PERFUSION IMAGING - APPLICATION TO MAGNETIC-RESONANCE-IMAGING SO INVESTIGATIVE RADIOLOGY LA English DT Article DE BRAIN ACTIVATION; CEREBRAL BLOOD FLOW; FUNCTIONAL IMAGING; PERFUSION ID CEREBRAL BLOOD-FLOW; CONTRAST; NMR; SUSCEPTIBILITY; TOMOGRAPHY; (H2O)-O-17; DIFFUSION; BRAIN; MRI AB Perfusion magnetic resonance imaging (MRI) offers relative safety (no ionizing radiation), high spatial/temporal resolution, multi-orientation imaging capability, and relative low cost when compared with sophisticated techniques, such as positron emission tomography (PET). Several methods have been recently proposed to image perfusion. Some techniques mimic conventional nuclear medicine principles, but use radioactively inert tracers. Other approaches directly use blood as an endogeneous natural tracer. Such methods are totally noninvasive, and offer original insights, for instance by monitoring variations in blood oxygenation in human brain cortex during activation tasks. These methods are presented and compared. Emphasis is given on advantages and drawbacks, and potential clinical applications. RP LEBIHAN, D (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,ROOM C660,BETHESDA,MD 20892, USA. NR 20 TC 18 Z9 19 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD DEC PY 1992 VL 27 SU 2 BP S6 EP S11 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KC700 UT WOS:A1992KC70000002 PM 1468877 ER PT J AU WILLIAMS, TF COHEN, GD AF WILLIAMS, TF COHEN, GD TI PREVENTING DISEASES OF AGING SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Letter RP WILLIAMS, TF (reprint author), US DEPT HHS,NIA,BETHESDA,MD 20014, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD WIN PY 1992 VL 8 IS 2 BP 15 EP 15 PG 1 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA GZ168 UT WOS:A1992GZ16800017 ER PT J AU MURATA, J SAIKI, I YONEDA, J AZUMA, I AF MURATA, J SAIKI, I YONEDA, J AZUMA, I TI DIFFERENCES IN CHEMOTAXIS TO FIBRONECTIN IN WEAKLY AND HIGHLY METASTATIC TUMOR-CELLS SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE METASTASIS; CHEMOTAXIS; FIBRONECTIN; VERY LATE ANTIGEN ID MELANOMA-CELLS; MIGRATION; HAPTOTAXIS; LAMININ; ADHESION; INVITRO; DOMAINS; INHIBITION; CARCINOMA; INVASION AB We have examined the chemotactic ability of tumor cell lines with different metastatic potential to plasma fibronectin in Transwell chamber assay. Human renal carcinoma cells with highly metastatic potential, SN12 C-2, chemotactically migrated to fibronectin (10 mug/ml) about three-fold more strongly than weakly metastatic SN12 C-4 cells. Similarly, murine melanoma B16-BL6 cells (highly metastatic) showed higher motility to soluble fibronectin in comparison with weakly metastatic B16-F1 cells. Anti-VLA-alpha3 and beta1 antibodies potently blocked the chemotaxis of both highly and weakly metastatic cells (SN12 C-2 and C-4) to fibronectin. This implies that the migration of both C-2 and C-4 cells to fibronectin is basically mediated by VLA-3 receptor. In contrast, the anti-VLA-alpha5 antibody and RGDS peptide significantly inhibited the chemotaxis of SN12 C-2 cells to fibronectin, but did not affect weakly metastatic SN12 C-4 celts. These results suggest that the chemotactic ability to fibronectin positively correlates with the metastatic potential in SN12 and B16 cell lines, and that VLA-5 receptor is concerned in the motility of highly metastatic SN12 C-2 cells to soluble fibronectin. C1 HOKKAIDO UNIV,INST IMMUNOL SCI,KITA 15,NISHI 7,KITA KU,SAPPORO,HOKKAIDO 060,JAPAN. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 34 TC 15 Z9 15 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD DEC PY 1992 VL 83 IS 12 BP 1327 EP 1333 PG 7 WC Oncology SC Oncology GA KD921 UT WOS:A1992KD92100015 PM 1483947 ER PT J AU PORTIS, JL MCATEE, FJ KAYMAN, SC AF PORTIS, JL MCATEE, FJ KAYMAN, SC TI INFECTIVITY OF RETROVIRAL DNA INVIVO SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Letter C1 PUBL HLTH RES INST CITY NEW YORK INC,RETROVIRAL BIOL LAB,NEW YORK,NY 10016. RP PORTIS, JL (reprint author), NIAID,ROCKY MTN LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 4 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC PY 1992 VL 5 IS 12 BP 1272 EP 1273 DI 10.1097/00126334-199212000-00011 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KA031 UT WOS:A1992KA03100011 PM 1453336 ER PT J AU BOWLER, S SHEON, AR DANGELO, LJ VERMUND, SH AF BOWLER, S SHEON, AR DANGELO, LJ VERMUND, SH TI HIV AND AIDS AMONG ADOLESCENTS IN THE UNITED-STATES - INCREASING RISK IN THE 1990S SO JOURNAL OF ADOLESCENCE LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NEW-YORK-CITY; SEXUALLY-TRANSMITTED DISEASES; INTRAVENOUS-DRUG-USERS; VIRUS-INFECTION; URBAN ADOLESCENTS; COLLEGE-STUDENTS; HOMELESS YOUTHS; SAN-FRANCISCO; KNOWLEDGE C1 NIAID,DIV AIDS,CLIN RES PROGRAM,EPIDEMIOL BRANCH,6003 EXECUT BLVD,BETHESDA,MD 20892. MAYATECH CORP,SILVER SPRING,MD. CHILDRENS NATL MED CTR,DEPT ADOLESCENT & YOUNG ADULT MED,WASHINGTON,DC. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT PAEDIAT,WASHINGTON,DC 20052. OI Vermund, Sten/0000-0001-7289-8698 NR 130 TC 46 Z9 46 U1 3 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0140-1971 J9 J ADOLESCENCE JI J. Adolesc. PD DEC PY 1992 VL 15 IS 4 BP 345 EP 371 DI 10.1016/0140-1971(92)90069-H PG 27 WC Psychology, Developmental SC Psychology GA KD819 UT WOS:A1992KD81900002 PM 1487574 ER PT J AU KALINER, MA AF KALINER, MA TI THE PHYSIOLOGY AND PATHOPHYSIOLOGY OF THE PARASYMPATHETIC NERVOUS-SYSTEM IN NASAL DISEASE - AN OVERVIEW SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT CONF ON INTRANASAL ANTICHOLINERGIC TREATMENT OF NASAL DISORDERS CY MAR 06, 1991 CL SAN FRANCISCO, CA SP BOEHRINGER INGELHEIM PHARM ID SECRETIONS; RHINITIS RP KALINER, MA (reprint author), NIAID,ALLERG DIS SECT,BLDG 10,ROOM 11C205,BETHESDA,MD 20892, USA. NR 8 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1992 VL 90 IS 6 SU S BP 1044 EP 1045 DI 10.1016/0091-6749(92)90120-Q PN 2 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA KD635 UT WOS:A1992KD63500003 PM 1460205 ER PT J AU SPECTOR DOCKHORN GEORGITIS WOOD MELTZER KALINER BARANIUK NACLERIO DRUCE AF SPECTOR DOCKHORN GEORGITIS WOOD MELTZER KALINER BARANIUK NACLERIO DRUCE TI INTRANASAL ANTICHOLINERGIC TREATMENT OF NASAL DISORDERS - SAN-FRANCISCO, CALIFORNIA MARCH 6, 1991 - QUESTIONS AND ANSWERS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Discussion C1 ALLERGY RES FDN,LOS ANGELES,CA. GEORGETOWN UNIV,MED CTR,MED CTR,DEPT MED,WASHINGTON,DC 20007. UNIV MISSOURI,SCH MED,KANSAS CITY,MO 64108. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63104. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. NIAID,ALLERG DIS SECT,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,ALLERGY & ASTHMA MED GRP & RES CTR,SAN DIEGO,CA 92103. JOHNS HOPKINS UNIV,SCH MED,CTR ASTHMA & ALLERGY,BALTIMORE,MD 21205. BOEHRINGER INGELHEIM PHARMACEUT INC,CLIN RES,RIDGEFIELD,CT. RP SPECTOR (reprint author), UNIV CALIF LOS ANGELES,SCH MED,ALLERGY MED CLIN,LOS ANGELES,CA 90024, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1992 VL 90 IS 6 SU S BP 1082 EP 1086 PN 2 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA KD635 UT WOS:A1992KD63500010 ER PT J AU FORTNEY, S TANKERSLEY, C LIGHTFOOT, JT DRINKWATER, D CLULOW, J GERSTENBLITH, G OCONNOR, F BECKER, L LAKATTA, E FLEG, J AF FORTNEY, S TANKERSLEY, C LIGHTFOOT, JT DRINKWATER, D CLULOW, J GERSTENBLITH, G OCONNOR, F BECKER, L LAKATTA, E FLEG, J TI CARDIOVASCULAR-RESPONSES TO LOWER-BODY NEGATIVE-PRESSURE IN TRAINED AND UNTRAINED OLDER MEN SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE ORTHOSTASIS; AGING; BLOOD PRESSURE; CARDIAC VOLUMES ID HEART-RATE VARIABILITY; ORTHOSTATIC TOLERANCE; HEALTHY-SUBJECTS; BLOOD POOL; UP TILT; AGE; VOLUME; ENDURANCE; HUMANS; CELLS AB To determine whether aerobic conditioning alters the orthostatic responses of older subjects, cardiovascular performance was monitored during graded lower body negative pressure in nine highly trained male senior athletes (A) aged 59-73 yr [maximum O2 uptake (VO2max) = 52.4 +/- 1.7 ml . kg-1 . min-1] and nine age-matched control subjects (C) (VO2max = 31.0 +/- 2.9 ml . kg-1 . min-1). Cardiac volumes were determined from gated blood pool scintigrams by use of Tc-99m-labeled erythrocytes. During lower body negative pressure (0 to -50 mmHg), left ventricular end-diastolic and end-systolic volume indexes and stroke volume index decreased in both groups while heart rate increased. The decreases in cardiac volumes and mean arterial pressure and the increase in heart rate between 0 and -50 mmHg were significantly less in A than in C. For example, end-diastolic volume index decreased by 32 +/- 4 ml in C vs. 14 +/- 2 ml in A (P < 0.01), mean arterial pressure declined 7 +/- 5 mmHg in C and increased by 5 +/- 3 mmHg in A (P < 0.05), and heart rate increased 13 +/- 3 beats/min in C and 7 +/- 1 beats/min in A (P < 0.05). These data suggest that increased VO2max among older men is associated with improved orthostatic responses. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. FU NCRR NIH HHS [RR02719]; NIA NIH HHS [P01-AG4402-05, N01-AG-9-2216] NR 41 TC 20 Z9 20 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 DEC PY 1992 VL 73 IS 6 BP 2693 EP 2700 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA KE844 UT WOS:A1992KE84400070 PM 1490987 ER PT J AU CHAN, CC LI, Q KIKUCHI, T SHINOHARA, T NUSSENBLATT, RB AF CHAN, CC LI, Q KIKUCHI, T SHINOHARA, T NUSSENBLATT, RB TI ENHANCEMENT OF S-ANTIGEN AND ITS MESSENGER-RNA IN THE IRIDES OF UVEITIC PATIENTS SO JOURNAL OF AUTOIMMUNITY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; EXPERIMENTAL ALLERGIC UVEITIS; BETA-ADRENERGIC-RECEPTOR; PINEAL-GLAND; RETINAL ANTIGENS; 48-KDA PROTEIN; BOVINE RETINA; ARRESTIN; DISEASE; TRANSCRIPTION C1 NEI,RETINAL CELLS & MOLEC BIOL LAB,BETHESDA,MD 20892. RP CHAN, CC (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N206,BETHESDA,MD 20892, USA. NR 37 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD DEC PY 1992 VL 5 IS 6 BP 719 EP 732 DI 10.1016/0896-8411(92)90188-V PG 14 WC Immunology SC Immunology GA KE488 UT WOS:A1992KE48800005 PM 1489485 ER PT J AU GENTRYWEEKS, CR HULTSCH, AL KELLY, SM KEITH, JM CURTISS, R AF GENTRYWEEKS, CR HULTSCH, AL KELLY, SM KEITH, JM CURTISS, R TI CLONING AND SEQUENCING OF A GENE ENCODING A 21-KILODALTON OUTER-MEMBRANE PROTEIN FROM BORDETELLA-AVIUM AND EXPRESSION OF THE GENE IN SALMONELLA-TYPHIMURIUM SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; ALCALIGENES-FAECALIS ISOLATE; ACUTE RESPIRATORY-DISEASE; OMPA GENE; PSEUDOMONAS-AERUGINOSA; NUCLEOTIDE-SEQUENCE; MOLECULAR CHARACTERIZATION; RECOMBINANT PLASMIDS; STABLE MAINTENANCE; RECEPTOR PROTEIN AB Three gene libraries of Bordetella avium 197 DNA were prepared in Escherichia coli LE392 by using the cosmid vectors pCP13 and pYA2329, a derivative of pCP13 specifying spectinomycin resistance. The cosmid libraries were screened with convalescent-phase anti-B. avium turkey sera and polyclonal rabbit antisera against B. avium 197 outer membrane proteins. One E. coli recombinant clone produced a 56-kDa protein which reacted with convalescent-phase serum from a turkey infected with B. avium 197. In addition, five E. coli recombinant clones were identified which produced B. avium outer membrane proteins with molecular masses of 21, 38, 40, 43, and 48 kDa. At least one of these E. coli clones, which encoded the 21-kDa protein, reacted with both convalescent-phase turkey sera and antibody against B. avium 197 outer membrane proteins. The gene for the 21-kDa outer membrane protein was localized by Tn5seq1 mutagenesis, and the nucleotide sequence was determined by dideoxy sequencing. DNA sequence analysis of the 21-kDa protein revealed an open reading frame of 582 bases that resulted in a predicted protein of 194 amino acids. Comparison of the predicted amino acid sequence of the gene encoding the 21-kDa outer membrane protein with protein sequences in the National Biomedical Research Foundation protein sequence data base indicated significant homology to the OmpA proteins of Shigella dysenteriae, Enterobacter aerogenes, E. coli, and Salmonella typhimurium and to Neisseria gonorrhoeae outer membrane protein III, Haemophilus influenzae protein P6, and Pseudomonas aeruginosa porin protein F. The gene (ompA) encoding the B. avium 21-kDa protein hybridized with 4.1-kb DNA fragments from EcoRI-digested, chromosomal DNA of Bordetella pertussis and Bordetella bronchiseptica and with 6.0- and 3.2-kb DNA fragments from EcoRI-digested, chromosomal DNA of B. avium and B. avium-like DNA, respectively. A 6.75-kb DNA fragment encoding the B. avium 21-kDa protein was subcloned into the Asd+ vector pYA292, and the construct was introduced into the avirulent DELTAcya DELTAcrp DELTAasd S. typhimurium chi3987 for oral immunization of birds. The gene encoding the 21-kDa protein was expressed equivalently in B. avium 197, DELTAasd E. coli chi6097, and S. typhimurium chi3987 and was localized primarily in the cytoplasmic membrane and outer membrane. In preliminary studies on oral inoculation of turkey poults with S. typhimurium chi3987 expressing the gene encoding the B. avium 21-kDa protein, it was determined that a single dose of the recombinant Salmonella vaccine failed to elicit serum antibodies against the 21-kDa protein and challenge with wild-type B. avium 197 resulted in colonization of the trachea and thymus with B. avium 197. C1 WASHINGTON UNIV,DEPT BIOL,ST LOUIS,MO 63130. RP GENTRYWEEKS, CR (reprint author), NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-28487, 1-F32-AI-07628] NR 73 TC 24 Z9 25 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 DEC PY 1992 VL 174 IS 23 BP 7729 EP 7742 PG 14 WC Microbiology SC Microbiology GA JZ841 UT WOS:A1992JZ84100030 PM 1447140 ER PT J AU HAYTHORNTHWAITE, JA ANDERSON, DE MOORE, LH AF HAYTHORNTHWAITE, JA ANDERSON, DE MOORE, LH TI SOCIAL AND BEHAVIORAL-FACTORS ASSOCIATED WITH EPISODES OF INHIBITORY BREATHING SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE RESPIRATION; AMBULATORY MONITORING; PSYCHOSOCIAL FACTORS; STRESS ID HYPERTENSION; SLEEP; RESPIRATION; REACTIVITY; STRESS; APNEA; DOGS AB Previous research has shown that episodes of inhibitory breathing, characterized by low-frequency breathing, occur both in laboratory animals during intervals preceding avoidance tasks and in humans in the natural environment. The present study investigated social and behavioral factors accompanying episodes of inhibitory breathing that occur in the natural environment. Breathing frequency and tidal volume of ambulatory subjects were monitored via inductive plethysmography. Information concerning location, social environment, behavior, and mood was self-recorded in a computerized diary. The percentage of episodes of inhibitory breathing was found to be significantly greater in social situations than when subjects were alone. Additional analyses eliminated talking as an explanation for these effects. Inhibitory breathing was more frequent when subjects were sedentary rather than active, and inhibitory breathing was not associated with changes in mood or appraisal. Additional research is needed to determine the nature of the social interactions that elicit inhibitory breathing, its physiological concomitants, and its long-term health implications. C1 NIA,BEHAV SCI LAB,BALTIMORE,MD 21224. NR 32 TC 7 Z9 7 U1 1 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD DEC PY 1992 VL 15 IS 6 BP 573 EP 588 DI 10.1007/BF00844857 PG 16 WC Psychology, Clinical SC Psychology GA KA294 UT WOS:A1992KA29400003 PM 1484381 ER PT J AU DIX, K BURKA, LT DAUTERMAN, WC AF DIX, K BURKA, LT DAUTERMAN, WC TI PHARMACOKINETICS OF PROPETAMPHOS FOLLOWING INTRAVENOUS ADMINISTRATION IN THE F344 RAT SO JOURNAL OF BIOCHEMICAL TOXICOLOGY LA English DT Article DE NONCOMPARTMENTAL PHARMACOKINETICS; PROPETAMPHOS; RAT ID METABOLISM AB Propetamphos [(E)-1-methylethyl 3-[[(ethylamino)methoxyphosphinothioyl]oxy]-2-butenoatel, the active ingredient in Safrotin,(R) is an organophosphate developed by Sandoz, Ltd.(R) (Switzerland) as an insecticide (1). Although metabolism of propetamphos has been previously investigated (2,3), there is no pharmacokinetic data available in the literature. The current studies were undertaken to investigate the pharmacokinetics of propetamphos following intravenous administration in male and female Fischer 344 (F344) rats. Rats were dosed via an indwelling jugular cannula at a dose of 12 mg/kg (one-tenth the oral LD-50). Blood samples were withdrawn via the cannula at predetermined timepoints to quantitate plasma concentrations of propetamphos over time. Propetamphos is highly bound to plasma proteins (free fraction = 0.06). Free propetamphos concentration in plasma vs. time data were analyzed by noncompartmental methods. The terminal elimination rate constant, lambda, was significantly different for males versus females (0.015 min-1 for males and 0.037 min-1 for females, p = 0.001). Plasma was cleared of unbound propetamphos at rates of 0.559 +/- 0.069 and 0.828 +/- 0.181 L/min/kg for males and females (mean +/- standard error). Mean residence times (MRTs) for propetamphos in the body for males and females were 28.3 +/- 5.7 and 14.4 +/- 3.5 min, and the volume of distribution at steady state (Vss) was 14.7 +/- 2.6 and 12.3 +/- 4.5 L/kg. The differences in these parameters, clearance (CI), MRT, and Vss, were not statistically significant at the p < 0.05 level for males versus females, but MRT was nearly significantly different (p = 0.08). Because of the rapid elimination of propetamphos from plasma following intravenous administration, it is unlikely that propetamphos would bioaccumulate in environmentally exposed animals. Although the pharmacokinetic parameters were not statistically different for males and females in these studies, there was a clear clinical difference in their susceptibility to propetamphos toxicity. Female rats presented with overt signs of organophosphate intoxication, whereas males were only slightly effected. The observed gender-related clinical difference in susceptibility to toxicity suggests that there may be a difference in the extent of elimination due to activation versus detoxication of propetamphos in males and females. Another possible explanation for the clinical difference in propetamphos toxicity is that inhibition of acetylcholinesterase by the activated, oxygenated form of propetamphos (propetamphos oxon) may be greater in females than in males. C1 N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. RP DIX, K (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [ES-00044, ES-07046] NR 10 TC 3 Z9 3 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0887-2082 J9 J BIOCHEM TOXICOL JI J. Biochem. Toxicol. PD WIN PY 1992 VL 7 IS 4 BP 199 EP 204 DI 10.1002/jbt.2570070402 PG 6 WC Toxicology SC Toxicology GA KK447 UT WOS:A1992KK44700001 PM 1293308 ER PT J AU YAMAGUCHI, N KIMURA, S MCBRIDE, OW HORI, H YAMADA, Y KANAMORI, T YAMAKOSHI, H NAGAI, Y AF YAMAGUCHI, N KIMURA, S MCBRIDE, OW HORI, H YAMADA, Y KANAMORI, T YAMAKOSHI, H NAGAI, Y TI MOLECULAR-CLONING AND PARTIAL CHARACTERIZATION OF A NOVEL COLLAGEN CHAIN, ALPHA-1(XVI), CONSISTING OF REPETITIVE COLLAGENOUS DOMAINS AND CYSTEINE-CONTAINING NONCOLLAGENOUS SEGMENTS SO JOURNAL OF BIOCHEMISTRY LA English DT Article ID XII COLLAGEN; EXTRACELLULAR-MATRIX; IX COLLAGEN; GENES; ACID; LOCALIZATION; FAMILY AB In an effort to identify new members of the collagen family, we screened a human placenta cDNA library with a collagenous probe. A novel 3.7 kb cDNA was identified encoding an open reading frame of 1, 186 amino acids and containing a termination codon. The predicted polypeptide consists of 9 repetitive collagenous (stretches of Gly-X-Y) and several non-collagenous segments. Two cysteinyl residues separated by two amino acid residues (Cys-X-X-Cys) are regularly located in the N-terminal region of each non-collagenous segment. The deduced amino acid sequence described above is distinct from those of known types of collagen. Therefore, this novel collagen chain is designated alpha1(XVI). Northern blot analysis revealed an alpha1(XVI) mRNA of 5.2 kb, indicating that the overlapping cDNA clones isolated in this study covered nearly three-fourths of the mRNA. As a tool for further study on the expression of type XVI collagen, we prepared an antibody against the nonadecapeptide CFLSLERPRAEEARGDNSE, derived from the putative translation product of the cDNA. In immunoblot analysis, the antibody recognized a 160 kDa protein, which was bacterial collagenase-sensitive. Immunohistochemical stainings of human placental tissues with anti-peptide antibody revealed a positive reaction with amnion, the membranous tissue lining the amniotic cavity. The gene of alpha1(XVI) chain, COL16A1, is mapped on the short arm of human chromosome 1(1p13-p34). C1 TOKYO MED & DENT UNIV,MED RES INST,DEPT TISSUE PHYSIOL,2-3-10 KANDASURUGADAI,CHIYODA KU,TOKYO 101,JAPAN. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892. NR 35 TC 31 Z9 32 U1 0 U2 2 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD DEC PY 1992 VL 112 IS 6 BP 856 EP 863 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB752 UT WOS:A1992KB75200025 PM 1284248 ER PT J AU ZATZ, M AF ZATZ, M TI DOES THE CIRCADIAN PACEMAKER ACT THROUGH CYCLIC-AMP TO DRIVE THE MELATONIN RHYTHM IN CHICK PINEAL CELLS SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE CIRCADIAN RHYTHMS; FORSKOLIN; SEROTONIN N-ACETYLTRANSFERASE ID N-ACETYLTRANSFERASE ACTIVITY; PHOTOENDOCRINE TRANSDUCTION; CALCIUM INFLUX; LIGHT; GLAND; CAMP; OSCILLATION; SEROTONIN; PHASE; NOREPINEPHRINE AB Cyclic AMP is a key regulator of melatonin production in the chick pineal gland. Agents that raise cyclic AMP levels (such as forskolin), or cyclic AMP analogues (such as 8-bromocyclic AMP), increase melatonin synthesis and release, whereas agents that lower cyclic AMP levels (including light) decrease melatonin synthesis and release. A circadian oscillator in these cells also raises and lowers melatonin output. We have been investigating the relationships between cyclic AMP and the circadian pacemaker in the regulation of melatonin production. In the chick pineal (unlike certain neuronal systems), the weight of the evidence indicates that cyclic AMP is not on an entrainment pathway to the circadian pacemaker. Instead, cyclic AMP appears to act downstream from the pacemaker. The pacemaker might itself act directly through cyclic AMP, regulating melatonin content by raising and lowering cyclic AMP levels. If this were the case, and if the effects of cyclic AMP levels on melatonin output are saturable (as they must be), then, in the face of such saturating levels of cyclic AMP, the pacemaker should no longer raise or lower melatonin output. To test this prediction, maximally effective concentrations of forskolin and 8-bromocyclic AMP were determined. Both agents markedly increased melatonin output. After 36 hr, cells were refractory to additional stimulation of melatonin output by addition of both agents together, or by higher concentrations of forskolin (although cyclic AMP levels could still be raised further). Nonetheless, the circadian pacemaker continued to raise and lower melatonin output: The rhythm persisted in the face of saturating levels of cyclic AMP. It is therefore suggested that the circadian pacemaker in chick pineal cells acts with, not through, cyclic AMP to regulate melatonin synthesis. Cyclic AMP and the pacemaker act synergistically to regulate serotonin N-acetyltransferase activity and the melatonin rhythm, with cyclic AMP mediating acute effects and amplitude regulation. RP ZATZ, M (reprint author), NIMH,CELL BIOL LAB,BIOCHEM PHARMACOL SECT,BETHESDA,MD 20892, USA. NR 27 TC 31 Z9 31 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD WIN PY 1992 VL 7 IS 4 BP 301 EP 311 DI 10.1177/074873049200700404 PG 11 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA KF412 UT WOS:A1992KF41200003 PM 1337482 ER PT J AU SUMNER, SCJ JIANG, SP JERNIGAN, RL FERRETTI, JA AF SUMNER, SCJ JIANG, SP JERNIGAN, RL FERRETTI, JA TI CONFORMATIONAL-ANALYSIS OF RECEPTOR SELECTIVE TACHYKININ ANALOGS - SENKTIDE AND SEPTIDE SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID IMMUNOGENIC PEPTIDE-FRAGMENTS; HYDROGEN-BOND INTERACTIONS; OCCURRING AMINO-ACIDS; SUBSTANCE-P; NONBONDED INTERACTIONS; SECONDARY STRUCTURE; ENERGY PARAMETERS; WATER SOLUTION; NEUROKININ-B; AGONISTS AB The conformational behavior in solution of two receptor selective tachykinin agonists, senktide (succinyl-D-F-MeF-G-L-M-NH2) and septide (pQ-F-F-P-L-M-NH2) is described. Two dimensional cross relaxation NMR spectroscopy is used together with coupling constant data to obtain interproton distance constraints. These results are used in conjunction with semi-empirical energy computations to indicate favorable conformations. Senktide is found to have a high degree of conformational order which is attributed to rotational restriction associated with the N-methylation of phenylalanine. The lowest energy conformation in accord with the experimental interproton distances contains a beta-turn. Interproton distances indicate that septide exists as a random coil or in an extended chain conformation. Energy computations suggest that septide is primarily an extended chain with internal reorientation restricted by the proline residue. These results may be related to the selectivity of these peptides for different receptors, in that the analogs, with conformations more stable than tachykinins, are more receptor selective. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NCI,MATH BIOL LAB,DCBDC,BETHESDA,MD 20892. RP SUMNER, SCJ (reprint author), CHEM IND INST TOXICOL,6 DAVIS DR,RES TRIANGLE PK,NC 27709, USA. RI Jernigan, Robert/A-5421-2012 FU PHS HHS [N01-C0-74102] NR 24 TC 5 Z9 5 U1 0 U2 1 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 1992 VL 10 IS 3 BP 429 EP 439 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KH431 UT WOS:A1992KH43100001 PM 1283515 ER PT J AU SPORN, MB ROBERTS, AB AF SPORN, MB ROBERTS, AB TI TRANSFORMING GROWTH-FACTOR-BETA - RECENT PROGRESS AND NEW CHALLENGES SO JOURNAL OF CELL BIOLOGY LA English DT Review ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; RETINOBLASTOMA GENE-PRODUCT; TGF-BETA; FACTOR-BETA-1; EXPRESSION; INHIBITION; RECEPTOR; SYSTEM; HEART RP SPORN, MB (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 49 TC 735 Z9 760 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1992 VL 119 IS 5 BP 1017 EP 1021 DI 10.1083/jcb.119.5.1017 PG 5 WC Cell Biology SC Cell Biology GA KA675 UT WOS:A1992KA67500001 PM 1332976 ER PT J AU BAINES, IC BRZESKA, H KORN, ED AF BAINES, IC BRZESKA, H KORN, ED TI DIFFERENTIAL LOCALIZATION OF ACANTHAMOEBA MYOSIN-I ISOFORMS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HEAVY-CHAIN KINASE; PLASMA-MEMBRANE; CASTELLANII; PROTEINS; BINDING; PURIFICATION; SITES; LOCUS AB Acanthamoeba myosins IA and IB were localized by immunofluorescence and immunoelectron microscopy in vegetative and phagocytosing cells and the total cell contents of myosins IA, IB, and IC were quantified by immunoprecipitation. The quantitative distributions of the three myosin I isoforms were then calculated from these data and the previously determined localization of myosin IC. Myosin IA occurs almost exclusively in the cytoplasm, where it accounts for approximately 50% of the total myosin I, in the cortex beneath phagocytic cups and in association with small cytoplasmic vesicles. Myosin IB is the predominant isoform associated with the plasma membrane, large vacuole membranes and phagocytic membranes and accounts for almost half of the total myosin I in the cytoplasm. Myosin IC accounts for a significant fraction of the total myosin I associated with the plasma membrane and large vacuole membranes and is the only myosin I isoform associated with the contractile vacuole membrane. These data suggest that myosin IA may function in cytoplasmic vesicle transport and myosin I-mediated cortical contraction, myosin IB in pseudopod extension and phagocytosis, and myosin IC in contractile vacuole function. In addition, endogenous and exogenously added myosins IA and IB appeared to be associated with the cytoplasmic surface of different subpopulations of purified plasma membranes implying that the different myosin I isoforms are targeted to specific membrane domains through a mechanism that involves more than the affinity of the myosins for anionic phospholipids. RP NHLBI, CELL BIOL LAB, BETHESDA, MD 20892 USA. RI Korn, Edward/F-9929-2012 NR 34 TC 100 Z9 100 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1992 VL 119 IS 5 BP 1193 EP 1203 DI 10.1083/jcb.119.5.1193 PG 11 WC Cell Biology SC Cell Biology GA KA675 UT WOS:A1992KA67500016 PM 1447297 ER PT J AU PARALKAR, VM WEEKS, BS YU, YM KLEINMAN, HK REDDI, AH AF PARALKAR, VM WEEKS, BS YU, YM KLEINMAN, HK REDDI, AH TI RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN 2B STIMULATES PC12 CELL-DIFFERENTIATION - POTENTIATION AND BINDING TO TYPE-IV COLLAGEN SO JOURNAL OF CELL BIOLOGY LA English DT Article ID FIBROBLAST GROWTH-FACTOR; AMINO-ACID SEQUENCE; BASEMENT-MEMBRANE; LAMININ; OSTEOGENIN; RECEPTOR; IDENTIFICATION; PURIFICATION; PRECURSOR; DOMAINS AB Bone morphogenetic protein 2B (BMP 2B, also known as BMP 4) induces cartilage and bone morphogenesis in ectopic extraskeletal sites. BMP 2B is one of several bone morphogenetic proteins which along with activins and inhibins are members of the transforming growth factor-beta (TGF-beta) family. Both BMP 2B and activin A, but not TGF-beta1, induce rat pheochromocytoma PC12 neuronal cell differentiation and expression of VGF, a nervous system-specific mRNA. PC12 cells exhibited approximately 2,500 receptors per cell for BMP 2B with an apparent dissociation constant of 19 pM. Extracellular matrix components, including fibronectin, laminin, and collagen type IV potentiated the activity of BMP and activin A, with the latter being the most active. Direct experiments demonstrated that radioiodinated BMP 2B bound to collagen type IV better than to either laminin or fibronectin. These data demonstrate a common neurotrophic activity of both BMP 2B and activin A, and suggest that these regulatory molecules alone and in conjunction with extracellular matrix components may play a role in both the development and repair of nervous tissue. C1 NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP REDDI, AH (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT ORTHOPAED SURG,MUSCULOSKELETAL CELL BIOL LAB,BALTIMORE,MD 21205, USA. NR 36 TC 129 Z9 132 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1992 VL 119 IS 6 BP 1721 EP 1728 DI 10.1083/jcb.119.6.1721 PG 8 WC Cell Biology SC Cell Biology GA KD077 UT WOS:A1992KD07700031 PM 1469059 ER PT J AU THOMAS, LA YAMADA, KM AF THOMAS, LA YAMADA, KM TI CONTACT STIMULATION OF CELL-MIGRATION SO JOURNAL OF CELL SCIENCE LA English DT Article DE CELL MIGRATION; NEURAL CREST; MELANOMA ID NEURAL CREST CELLS; INHIBITION; EMBRYO AB Mass migrations of dense cell populations occur periodically during embryonic development. It is known that extracellular matrices, through which the cells migrate, facilitate locomotion. However, this does not explain how cells, such as neural crest, can migrate as a dense cohort of cells in essentially continuous contact with one another. We report here that unique behavioral characteristics of the migrating cells may contribute to cohesive migration. We used time-lapse video microscopy to analyze the migration of quail neural crest cells and of two crest derivatives, human melanoma cells and melanocytes. These cells migrated poorly, if at all, when isolated, but could be stimulated up to 200-fold to travel following contact with migrating cells. This phenomenon, which we have termed ''contact-stimulated migration,'' appeared to activate and sustain migration of the mass of cells. Cells that became dissociated from the others ceased directional migration, thereby limiting aberrant cell dispersion. Fibroblasts were minimally responsive to this novel phenomenon, which may be crucial for major, mass cell migrations. RP THOMAS, LA (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 17 TC 53 Z9 53 U1 2 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD DEC PY 1992 VL 103 BP 1211 EP 1214 PN 4 PG 4 WC Cell Biology SC Cell Biology GA KF928 UT WOS:A1992KF92800034 PM 1487497 ER PT J AU TAKEDA, K GOSIEWSKA, A PETERKOFSKY, B AF TAKEDA, K GOSIEWSKA, A PETERKOFSKY, B TI SIMILAR, BUT NOT IDENTICAL, MODULATION OF EXPRESSION OF EXTRACELLULAR-MATRIX COMPONENTS DURING INVITRO AND INVIVO AGING OF HUMAN SKIN FIBROBLASTS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID MESSENGER-RNA LEVELS; COLLAGEN GENE-EXPRESSION; REPLICATIVE SENESCENCE; CELLULAR SENESCENCE; WERNERS SYNDROME; GROWTH; FIBRONECTIN; PROTEOGLYCAN; CARTILAGE; AGE AB Regulation of the synthesis of procollagen and other extracellular matrix components was examined in human skin fibroblasts obtained from donors of various ages, from fetal to 80 years old (in vivo aged), and in fetal fibroblasts at varying passage levels (in vitro aged). Growth rates and saturation densities of fibroblasts decreased with increasing age of the donor and after passage 20 of fetal fibroblasts. The rates of collagen and proteoglycan synthesis also decreased during both types of aging to about 10-25% of the rate in early passage fetal fibroblasts, whereas the synthesis of total noncollagenous proteins was not greatly affected. Decreased collagen synthesis in both types of aging was correlated with lower steady-state levels of mRNAs for the two subunits of type I procollagen mRNA, although their regulation was not coordinate. Type III collagen mRNA levels also declined in both types of aging. The concentration of fibronectin mRNA also decreased during in vitro aging but more rapidly than the collagen mRNAs, whereas in fibroblasts from 51-80-year-old donors, it was similar to or higher than in early passage fetal fibroblasts. This study suggests that the decreased synthesis of procollagen and proteoglycans in in vivo aged fibroblasts represents changes that are responsible for intrinsic degenerative changes that occur in human skin during aging. Furthermore, although in vitro and in vivo aging were similar in many respects, they were not equivalent, as evidenced by the differences in regulation of fibronectin expression. C1 NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. NR 44 TC 78 Z9 80 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1992 VL 153 IS 3 BP 450 EP 459 DI 10.1002/jcp.1041530303 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JZ909 UT WOS:A1992JZ90900002 PM 1447307 ER PT J AU GRANT, DS KINSELLA, JL FRIDMAN, R AUERBACH, R PIASECKI, BA YAMADA, Y ZAIN, M KLEINMAN, HK AF GRANT, DS KINSELLA, JL FRIDMAN, R AUERBACH, R PIASECKI, BA YAMADA, Y ZAIN, M KLEINMAN, HK TI INTERACTION OF ENDOTHELIAL-CELLS WITH A LAMININ-A CHAIN PEPTIDE (SIKVAV) INVITRO AND INDUCTION OF ANGIOGENIC BEHAVIOR INVIVO SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CAPILLARY-LIKE STRUCTURES; AMINO-ACID-SEQUENCE; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; SYNTHETIC PEPTIDE; GROWTH-FACTOR; NEURITE OUTGROWTH; DNA-SYNTHESIS; COLLAGENASE; DIFFERENTIATION AB Endothelial cells are known to bind to laminin, and two peptides derived from the laminin A (CTFALRGDNP) and B1(CDPGYIGSR) chains block the capillary-like tube formation on a laminin-rich basement membrane matrix, Matrigel. In the present study, we have used various in vitro and in vivo assays to investigate the angiogenic-biologic effects of a third active site in the laminin A chain, CS-RARKQAASIKVAVSADR (designated PA22-2) on endothelial cells. The SIKVAV-containing peptide was as active as the YIGSR-containing peptide for endothelial cell attachment but was less active than either the RGD-containing peptide or intact laminin. Endothelial cells seeded on this peptide appeared fibroblastic with many extended processes, unlike the normal cobblestone morphology observed on tissue culture plastic. In addition, in contrast to normal tube formation on Matrigel, short irregular structures formed, some of which penetrated the matrix and sprouting was more apparent. Analysis of endothelial cell conditioned media of cells cultured in the presence of this peptide indicated degradation of the Matrigel and zymograms demonstrated active collagenase IV (gelatinase) at 68 and 62 Kd. A murine in vivo angiogenesis assay and the chick yolk sac/chorioallantoic membrane assays with the peptide demonstrated increased endothelial cell mobilization, capillary branching, and vessel formation. These data suggest that the -SIKVAV-site may play an important role in initiating branching and formation of new capillaries from the parent vessels, a behavior that is observed in vivo in response to tumor growth or in the normal vascular response to injury. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. UNIV WISCONSIN,CTR DEV BIOL,MADISON,WI 53706. RP GRANT, DS (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 57 TC 128 Z9 130 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1992 VL 153 IS 3 BP 614 EP 625 DI 10.1002/jcp.1041530324 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JZ909 UT WOS:A1992JZ90900023 PM 1280280 ER PT J AU TAYLOR, SI AF TAYLOR, SI TI EDITORIAL - THE HUNT FOR MUTATIONS CAUSING NONINSULIN-DEPENDENT DIABETES-MELLITUS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GENE RP TAYLOR, SI (reprint author), NIDDKD, DIABET BRANCH, BLDG 10, ROOM 8S-239, BETHESDA, MD 20892 USA. NR 9 TC 3 Z9 3 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 DEC PY 1992 VL 75 IS 6 BP 1401 EP 1403 DI 10.1210/jc.75.6.1401 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KD201 UT WOS:A1992KD20100003 PM 1464639 ER PT J AU OERTER, KE SOBEL, AM ROSE, SR CRISTIANO, A MALLEY, JD CUTLER, GB BARON, J AF OERTER, KE SOBEL, AM ROSE, SR CRISTIANO, A MALLEY, JD CUTLER, GB BARON, J TI COMBINING INSULIN-LIKE GROWTH FACTOR-I AND MEAN SPONTANEOUS NIGHTTIME GROWTH-HORMONE LEVELS FOR THE DIAGNOSIS OF GROWTH-HORMONE DEFICIENCY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOMEDIN-C; SHORT STATURE; CHILDREN; SECRETION; THERAPY; PUBERTY; HUMANS; HEIGHT AB There is no gold standard for the diagnosis of GH deficiency. Recent data show that spontaneous GH levels may lack sensitivity, and that GH stimulation tests lack specificity as currently performed. Serum insulin-like growth factor-I (IGF-I) measurements lack both sensitivity and specificity. Some of these problems may be explained by nutritional effects. In children, overnutrition decreases GH and increases IGF-I, while undernutrition decreases IGF-I and increases GH. To overcome these difficulties and improve diagnostic accuracy, we combined mean spontaneous nighttime GH levels with IGF-I levels in a statistically based bivariate model. On a two-dimensional plot of mean spontaneous nighttime GH level (in SD units) vs. IGF-I level (in SD units), we defined a new variable, S (sum) score, where S(1/square-root 2) x (nighttime mean GH SD + IGF-I SD). While IGF-I (SD) and the mean spontaneous nighttime GH (SD) showed a significant correlation with body mass index, the S score was independent of body mass. We, therefore, used the S score to define a new test for GH deficiency. A child failed this bivariate test if his S score was less than -2 SD. We applied this model to 47 normal children and 48 short or slowly growing children (all prepubertal). We measured spontaneous nighttime GH levels and IGF-I levels in all children. In addition, the short children underwent 3 GH stimulation tests. Forty-six of the 47 normal children passed the bivariate test for GH sufficiency. Twenty-three of the 48 short or slowly growing children failed the bivariate test, whereas only 11 children had an abnormally low mean spontaneous nighttime GH measurement alone. Sixteen of 23 children who were GH deficient by the bivariate test were also GH deficient by the stimulation tests. In summary, the bivariate test for GH deficiency appears 1) to be independent of body mass, unlike either IGF-I or GH individually; 2) to identify more children than the mean spontaneous nighttime GH level alone; and 3) to be highly specific in the normal population, unlike stimulation tests. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIH, STAT & MATH METHODOL LAB, BETHESDA, MD 20892 USA. RP OERTER, KE (reprint author), NIH, DIV COMP RES & TECHNOL, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 27 TC 19 Z9 19 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 DEC PY 1992 VL 75 IS 6 BP 1413 EP 1420 DI 10.1210/jc.75.6.1413 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KD201 UT WOS:A1992KD20100006 PM 1464642 ER PT J AU MEDEIROS, LJ ANASTI, J GARDNER, KL PASS, HI NIEMAN, LK AF MEDEIROS, LJ ANASTI, J GARDNER, KL PASS, HI NIEMAN, LK TI VIRILIZING ADRENAL-CORTICAL NEOPLASM ARISING ECTOPICALLY IN THE THORAX SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID OVARIAN; TUMORS AB We describe a 44-yr-old woman with a 12-yr history of clinical virilization and serum testosterone levels up to 28.1 nmol/L (normal range, 1-3.3 nmol/L) in whom repeated clinical evaluation and surgical procedures failed to reveal the source of androgen production. At the time the patient was referred to the Clinical Center of the NIH, an intrathoracic mass was seen on upper cuts of an abdominal computer-aided tomography scan, confirmed by computer-aided tomography scan and magnetic resonance imaging of the chest. A 6 x 5 x 3.5-cm mass, attached to the posterior pericardium, was removed by thoracotomy. Pathological examination revealed an adrenal cortical neoplasm of uncertain malignant potential that contained testosterone, 11-deoxycortisol, progesterone, and 17-hydroxyprogesterone. After the operation, the patient's serum testosterone levels decreased to the normal range. Ectopic adrenal cortical rests in the thorax and neoplasms arising from these rests are extremely rare, and we are not aware of a similar case previously reported. In women with virilization, radiological studies of the thorax as well as other reported sites of ectopic adrenal cortex should be performed if radiological studies of the abdomen and pelvis fail to locate the source of the neoplasm. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NCI, SURG PROGRAM, BETHESDA, MD 20892 USA. NR 26 TC 13 Z9 14 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 DEC PY 1992 VL 75 IS 6 BP 1522 EP 1525 DI 10.1210/jc.75.6.1522 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KD201 UT WOS:A1992KD20100027 PM 1464658 ER PT J AU SARTOR, O MCLELLAN, CA MYERS, CE BORNER, MM AF SARTOR, O MCLELLAN, CA MYERS, CE BORNER, MM TI SURAMIN RAPIDLY ALTERS CELLULAR TYROSINE PHOSPHORYLATION IN PROSTATE-CANCER CELL-LINES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE EPITHELIAL CELL LINES; POLYANIONS; PROSTATE; SURAMIN; TYROSINE PHOSPHORYLATION ID FIBROBLAST GROWTH-FACTOR; FACTOR RECEPTOR; PHOSPHOLIPASE-C; LUNG-CANCER; PROTEIN; TRANSFORMATION; INHIBITION; PDGF; ASSOCIATION; EXPRESSION AB Suramin, a synthetic polysulfonated anionic compound, is known to abrogate the activity of a variety of growth factors that serve as ligands for receptor-class protein-tyrosine kinases. Based on this information, we initially hypothesized that suramin treatment would be associated with decreased tyrosine phosphorylation. Upon testing this hypothesis in prostate cancer cell lines, we found that the most conspicuous effect of suramin was to increase the tyrosine phosphorylation of several distinct proteins. Further analyses indicate that suramin-induced increases in tyrosine phosphorylation represent a generalized, but not universal, phenomenon found in cell lines derived from a variety of human tissues. These rapid and specific suramin-induced alterations represent a novel finding for a non-polypeptide pharmaceutical agent and question the hypothesis that suramin exerts its antitumor action simply by abrogation of growth factor action. RP SARTOR, O (reprint author), NCI, DIV CANC TREATMENT, CLIN PHARMACOL BRANCH, BLDG 10, ROOM 12N226, BETHESDA, MD 20892 USA. RI Borner, Markus/B-7583-2011 NR 39 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1992 VL 90 IS 6 BP 2166 EP 2174 DI 10.1172/JCI116102 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE763 UT WOS:A1992KE76300003 PM 1281826 ER PT J AU COOPER, MJ STEINBERG, SM CHATTEN, J EVANS, AE ISRAEL, MA AF COOPER, MJ STEINBERG, SM CHATTEN, J EVANS, AE ISRAEL, MA TI PLASTICITY OF NEUROBLASTOMA TUMOR-CELLS TO DIFFERENTIATE ALONG A FETAL ADRENAL GANGLIONIC LINEAGE PREDICTS FOR IMPROVED PATIENT SURVIVAL SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE NEUROBLASTOMA; DIFFERENTIATION; NEURAL CREST; HNK-1; PROGNOSTIC MARKER ID NEURAL CREST DERIVATIVES; LONG-TERM SURVIVAL; CHROMAFFIN CELLS; BLASTOMA CELLS; GROWTH-FACTORS; EXPRESSION; GLUCOCORTICOIDS; PROGNOSIS; CHILDREN; FATE AB We have recently presented a model of human adrenal medullary histogenesis that incorporates all neural crest-derived lineages (chromaffin, sustentacular, and ganglionic) known to compose this tissue. To determine if neuroblastomas correspond to the arrested maturation of embryonal adrenal medullary cells, we evaluated the expression of adrenal medullary developmental markers in 81 neuroblastoma tumors. We found that patterns of chromaffin-related gene expression in these tumors correlated exactly with the patterns observed during maturation of adrenal medullary cells (P2 < 10(-5)). In a multivariate Cox proportional hazards analysis of developmental marker expression and other well-recognized prognostic variables, evidence of maturation along a fetal ganglionic lineage, as monitored by HNK-1 immunoreactivity (relative risk of 6.42, P2 = 0.0001), and age at diagnosis (relative risk of 5.05, P2 = 0.0042) were independent and significant prognostic indicators of patient survival. These studies demonstrate that neuroblastomas correspond to embryonal adrenal medullary cells arrested at recognizable stages during development, and that evidence of maturation along a fetal ganglionic lineage appears to have major importance in predicting patient survival. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. CHILDRENS HOSP PHILADELPHIA,DEPT PATHOL,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DEPT ONCOL,PHILADELPHIA,PA 19104. NR 45 TC 23 Z9 23 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1992 VL 90 IS 6 BP 2402 EP 2408 DI 10.1172/JCI116131 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE763 UT WOS:A1992KE76300032 PM 1281833 ER PT J AU CROFFORD, LJ SANO, H KARALIS, K WEBSTER, EL GOLDMUNTZ, EA CHROUSOS, GP WILDER, RL AF CROFFORD, LJ SANO, H KARALIS, K WEBSTER, EL GOLDMUNTZ, EA CHROUSOS, GP WILDER, RL TI LOCAL SECRETION OF CORTICOTROPIN-RELEASING HORMONE IN THE JOINTS OF LEWIS RATS WITH INFLAMMATORY ARTHRITIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE NEUROPEPTIDE; STREPTOCOCCAL CELL WALL ARTHRITIS; ADJUVANT ARTHRITIS; HYPOTHALAMIC PITUITARY ADRENAL AXIS; SUBSTANCE-P; GLUCOCORTICOIDS ID PITUITARY-ADRENAL AXIS; CENTRAL NERVOUS-SYSTEM; WALL-INDUCED ARTHRITIS; SUBSTANCE-P; FACTOR RECEPTORS; SYMPATHETIC EFFERENTS; MOUSE SPLEEN; SPINAL-CORD; CELLS; LOCALIZATION AB Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, is also secreted in peripheral inflammatory sites, where it acts as a local proinflammatory agent. Arthritis-susceptible LEW/N rats have profoundly deficient hypothalamic CRH responses to inflammatory stimuli and other stressors. Arthritis-resistant F344/N rats, on the other hand, have a robust increase in hypothalamic CRH in response to the same stimuli. Contrasting with these hypothalamic CRH responses, we now show that CRH expression is markedly increased in the joints and surrounding tissues of LEW/N rats with streptococcal cell wall- and adjuvant-induced arthritis, whereas it is not increased in similarly treated F344/N rats and is only transiently increased in congenitally athymic nude LEW.rnu/rnu rats. Glucocorticoid treatment suppressed, but did not eliminate, CRH immunoreactivity in the joints of LEW/N rats. CRH mRNA was present in inflamed synovia, as well as in spinal cord, and inflamed synovia also expressed specific CRH-binding sites. We compared CRH expression in inflamed joints with another well-characterized proinflammatory neuropeptide, substance P (SP), and found that SP immunoreactivity paralleled that of CRH. In summary, although LEW/N rats have deficient hypothalamic CRH responses to inflammatory stimuli compared with F344/N rats, they express relatively high levels of CRH at the site of inflammation. Analogous to SP, CRH may be delivered to the inflammatory site by peripheral nerves and/or synthesized at the inflammatory site. These data provide further support for the concept that CRH not only triggers the pituitary-adrenal antiinflammatory cascade, but also functions as an antithetically active local mediator of acute and chronic inflammatory arthritis. These data also illustrate the complex interrelationships of the nervous, endocrine, immune, and inflammatory systems. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP CROFFORD, LJ (reprint author), NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BLDG 10,ROOM 9N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Crofford, Leslie/J-8010-2013 NR 58 TC 177 Z9 177 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1992 VL 90 IS 6 BP 2555 EP 2564 DI 10.1172/JCI116150 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE763 UT WOS:A1992KE76300051 PM 1281840 ER PT J AU POLACHECK, I NAGLER, A OKON, E DRAKOS, P PLASKOWITZ, J KWONCHUNG, KJ AF POLACHECK, I NAGLER, A OKON, E DRAKOS, P PLASKOWITZ, J KWONCHUNG, KJ TI ASPERGILLUS-QUADRILINEATUS, A NEW CAUSATIVE AGENT OF FUNGAL SINUSITIS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID CHRONIC GRANULOMATOUS-DISEASE; NIDULANS; CHILDHOOD; INFECTION AB Aspergillus quadrilineatus was found to be the etiologic agent of pansinusitis in a patient suffering from acute nonlymphoblastic leukemia and who had undergone allogeneic bone marrow transplantation. A. quadrilineatus was cultured from biopsy specimens of the maxillary sinus, and tissue sections with fungal stains showed a necrotic area containing dichotomously branching septate hyphae, which is morphologically consistent with Aspergillus species. The patient was successfully treated with a combination of surgical debridement, granulocyte transfusions, and intravenous administration of amphotericin B-cholesterol sulfate colloidal dispersion. This is the first report of an infection caused by A. quadrilineatus. C1 NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BETHESDA,MD 20892. HADASSAH MED CTR,DEPT CLIN MICROBIOL,JERUSALEM,ISRAEL. HADASSAH MED CTR,DEPT BONE MARROW TRANSPLANTAT,JERUSALEM,ISRAEL. HADASSAH MED CTR,DEPT PATHOL,JERUSALEM,ISRAEL. USDA,SYSTEMAT BOT MYCOL & NEMATOL LAB,BELTSVILLE,MD 20705. NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BETHESDA,MD 20892. NR 15 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1992 VL 30 IS 12 BP 3290 EP 3293 PG 4 WC Microbiology SC Microbiology GA JZ911 UT WOS:A1992JZ91100052 PM 1452721 ER PT J AU FOSS, FM IHDE, DC BRENEMAN, DL PHELPS, RM FISCHMANN, AB SCHECHTER, GP LINNOILA, I BRENEMAN, JC COTELINGAM, JD GHOSH, BC STEINBERG, SM LYNCH, JW PHARES, JC STOCKER, JL BASTIAN, A SAUSVILLE, EA AF FOSS, FM IHDE, DC BRENEMAN, DL PHELPS, RM FISCHMANN, AB SCHECHTER, GP LINNOILA, I BRENEMAN, JC COTELINGAM, JD GHOSH, BC STEINBERG, SM LYNCH, JW PHARES, JC STOCKER, JL BASTIAN, A SAUSVILLE, EA TI PHASE-II STUDY OF PENTOSTATIN AND INTERMITTENT HIGH-DOSE RECOMBINANT INTERFERON ALFA-2A IN ADVANCED MYCOSIS-FUNGOIDES SEZARY-SYNDROME SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID T-CELL LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ELECTRON-BEAM RADIATION; LEUKOCYTE-A-INTERFERON; THERAPY; 2'-DEOXYCOFORMYCIN; TRIAL; PHOTOCHEMOTHERAPY; DEOXYCOFORMYCIN; DISSEMINATION C1 USN HOSP,NCI,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. VET AFFAIRS MED CTR,WASHINGTON,DC. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. UNIV CINCINNATI,MED CTR,CINCINNATI,OH 45267. NR 45 TC 63 Z9 63 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 DEC PY 1992 VL 10 IS 12 BP 1907 EP 1913 PG 7 WC Oncology SC Oncology GA KA722 UT WOS:A1992KA72200012 PM 1453206 ER PT J AU MUELLER, BU SKELTON, J CALLENDER, DPE MARSHALL, D GRESS, J LONGO, D NORTON, J RUBIN, M VENZON, D PIZZO, PA AF MUELLER, BU SKELTON, J CALLENDER, DPE MARSHALL, D GRESS, J LONGO, D NORTON, J RUBIN, M VENZON, D PIZZO, PA TI A PROSPECTIVE RANDOMIZED TRIAL COMPARING THE INFECTIOUS AND NONINFECTIOUS COMPLICATIONS OF AN EXTERNALIZED CATHETER VERSUS A SUBCUTANEOUSLY IMPLANTED DEVICE IN CANCER-PATIENTS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ONCOLOGY PATIENTS; VENOUS ACCESS; EXPERIENCE; CHILDREN; SYSTEM; THERAPY C1 NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 17 TC 146 Z9 149 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1992 VL 10 IS 12 BP 1943 EP 1948 PG 6 WC Oncology SC Oncology GA KA722 UT WOS:A1992KA72200017 PM 1453208 ER PT J AU COOPER, M MYERS, C AF COOPER, M MYERS, C TI SURAMIN FOR PROSTATE CARCINOMA - REPLY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter RP COOPER, M (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1992 VL 10 IS 12 BP 1985 EP 1986 PG 2 WC Oncology SC Oncology GA KA722 UT WOS:A1992KA72200027 ER PT J AU BUCKLEY, JW HEDNER, T MASOTTO, C POSVAR, E NEGROVILLAR, A CUBEDDU, LX AF BUCKLEY, JW HEDNER, T MASOTTO, C POSVAR, E NEGROVILLAR, A CUBEDDU, LX TI COMPARATIVE EFFECTS OF VERAPAMIL AND VOLUME OVERLOAD ON ATRIAL NATRIURETIC FACTORS AND THE RENIN-ANGIOTENSIN ALDOSTERONE-VASOPRESSIN SYSTEM SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID ESSENTIAL-HYPERTENSION; PEPTIDE; PLASMA; ATRIOPEPTIN; INFUSION; RELEASE; HEART; RAT; HOMEOSTASIS; ANTAGONISTS AB The authors compared the effects of verapamil (120 mg three times daily for 3 days) with those of acute volume expansion with normal saline on the plasma levels of atrial natriuretic factors (ANF), renin (PRA), angiotensin II (AII), aldosterone (ALD), and arginine-vasopressin (AVP) in healthy subjects. A randomized, double-blind, placebo-controlled study of crossover design was employed, where each individual received two acute volume overloads 1 week apart, one during placebo and the other during treatment with verapamil. Verapamil reduced blood pressure (BP) and increased the plasma levels of ANF, PRA, AII, ALD, and AVP. Strong positive correlations were observed between PRA, AII, ALD, and AVP, but not with ANF. Acute volume expansion (1500 mL saline in 15 minutes, in supine legs-up position) similarly to verapamil increased ANF levels; however, opposite to verapamil, it reduced PRA-AII-ALD, did not modify AVP levels, and increased BP. The mechanisms of these changes are discussed. In verapamil-treated subjects, volume expansion produced an additional increase in ANF and inhibited the PRA-AII-ALD axis, suggesting that in young healthy individuals, verapamil does not interfere with the reflex compensatory hormonal mechanisms activated under circumstances of acute volume-salt overload, with rapid expansion of the central vascular compartment. Our study indicates that verapamil and volume expansion represent two different stimuli for ANF secretion associated with opposite changes in the PRA-AII-ALD axis. In addition, verapamil can be used as a tool to study and understand the simultaneous increases in ANF and in PRA, AII, ALD, and AVP, characteristics of congestive heart failure. C1 UNIV N CAROLINA,DEPT PHARMACOL,DIV CLIN PHARMACOL,CHAPEL HILL,NC 27514. NIEHS,DEPT HLTH & HUMAN SERV,RES TRIANGLE PK,NC 27709. RP CUBEDDU, LX (reprint author), AVE LOS SAMANES,RES FLORIDA PALACE 8,LA FLORIDA,CARACAS,VENEZUELA. NR 30 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD DEC PY 1992 VL 32 IS 12 BP 1120 EP 1127 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KD102 UT WOS:A1992KD10200011 PM 1487551 ER PT J AU LINNOILA, M AF LINNOILA, M TI PSYCHOTROPIC MEDICATIONS AND TRAFFIC SAFETY SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material ID TRANQUILIZERS; PERFORMANCE; ACCIDENTS RP LINNOILA, M (reprint author), NIAAA,DIV INTRAMURAL CLIN & BIOL RES,BETHESDA,MD 20892, USA. NR 21 TC 3 Z9 3 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 1992 VL 12 IS 6 BP 384 EP 385 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA KA054 UT WOS:A1992KA05400003 PM 1474176 ER PT J AU BROWN, DW KETTER, TA CRUMLISH, J POST, RM AF BROWN, DW KETTER, TA CRUMLISH, J POST, RM TI CARBAMAZEPINE-INDUCED INCREASES IN TOTAL SERUM-CHOLESTEROL - CLINICAL AND THEORETICAL IMPLICATIONS SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DENSITY LIPOPROTEIN CHOLESTEROL; ENZYME-INDUCTION; BENZODIAZEPINE RECEPTORS; ANTISOCIAL PERSONALITY; ANTICONVULSANT DRUGS; EPILEPTIC CHILDREN; ADENYLATE-CYCLASE; APOLIPOPROTEIN-A; PANIC DISORDER; LIPIDS AB To assess the effect of carbamazepine (CBZ) upon total serum cholesterol, we examined 38 inpatients with affective illness and one with multiple personality disorder who received a course of CBZ monotherapy. CBZ therapy yielded significant increases in total serum cholesterol that became evident during the second week of therapy, persisted throughout therapy, and reversed in the first few weeks after discontinuation of therapy. CBZ-induced increases in total cholesterol appeared independent of initial mood state, diagnostic subtype, baseline cholesterol or thyroid indices; CBZ levels, doses, and level-to-dose ratios; and the degree of change in mood and thyroid indices. CBZ induction of enzymes mediating cholesterol synthesis is a possible mechanism of the increase in total cholesterol observed with CBZ therapy. Although preclinical studies suggest possible influence of cholesterol on neurotransmitter regulation and behavior, clinical studies have yielded conflicting data. There are insufficient data to support a role for cholesterol in the anti-convulsant and psychotropic mechanisms of CBZ. The increase in total serum cholesterol seen with CBZ therapy is likely due to an increase in the high density lipoprotein fraction and is thus not likely to be clinically problematic in relationship to atherosclerosis. C1 NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV ARKANSAS,SCH MED SCI,N LITTLE ROCK VA HOSP,LITTLE ROCK,AR 72204. NR 67 TC 34 Z9 34 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 1992 VL 12 IS 6 BP 431 EP 437 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA KA054 UT WOS:A1992KA05400009 PM 1474180 ER PT J AU GRADY, CL HAXBY, JV HORWITZ, B SCHAPIRO, MB RAPOPORT, SI UNGERLEIDER, LG MISHKIN, M CARSON, RE HERSCOVITCH, P AF GRADY, CL HAXBY, JV HORWITZ, B SCHAPIRO, MB RAPOPORT, SI UNGERLEIDER, LG MISHKIN, M CARSON, RE HERSCOVITCH, P TI DISSOCIATION OF OBJECT AND SPATIAL VISION IN HUMAN EXTRASTRIATE CORTEX - AGE-RELATED-CHANGES IN ACTIVATION OF REGIONAL CEREBRAL BLOOD-FLOW MEASURED WITH [O-15]WATER AND POSITRON EMISSION TOMOGRAPHY SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSTERIOR PARIETAL CORTEX; INFERIOR TEMPORAL NEURONS; MENTAL ROTATION; MACAQUE MONKEY; RHESUS-MONKEY; VISUAL AREA; FUNCTIONAL-PROPERTIES; SENSITIVITY; SPEED; COLOR AB We previously reported selective activation of regional cerebral blood flow (rCBF) in occipitotemporal cortex during a face matching task (object vision) and activation in superior parietal cortex during a dot-location matching task (spatial vision) in young subjects. The purpose of the present study was to determine the effects of aging on these extrastriate visual processing systems. Eleven young (mean age 27 +/- 4 years) and nine old (mean age 72 +/- 7 years) male subjects were studied. Positron emission tomographic scans were performed using a Scanditronix PC1024-7B tomograph and (H2O)-O-15 to measure rCBF. To locate brain areas that were activated by the visual tasks, pixel-by-pixel difference images were computed between images from a control task and images from the face and dot-location matching tasks. Both young and old subjects showed rCBF activation during face matching primarily in occipitotemporal cortex, and activation of superior parietal cortex during dot-location matching. Statistical comparisons of these activations showed that the old subjects had more activation of occipitotemporal cortex during the spatial task and more activation of superior parietal cortex during the object task than did the young subjects. These results show less functional separation of the dorsal and ventral visual pathways in older subjects, and may reflect an age-related reduction in the processing efficiency of these visual cortical areas. C1 NIMH,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. RP GRADY, CL (reprint author), NIA,LNS,BLDG 10,ROOM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 55 TC 86 Z9 88 U1 0 U2 3 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD WIN PY 1992 VL 4 IS 1 BP 23 EP 34 DI 10.1162/jocn.1992.4.1.23 PG 12 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA HB069 UT WOS:A1992HB06900003 PM 23967855 ER PT J AU MERCHENTHALER, I AF MERCHENTHALER, I TI ENKEPHALIN-IMMUNOREACTIVE NEURONS IN THE PARVICELLULAR SUBDIVISIONS OF THE PARAVENTRICULAR NUCLEUS PROJECT TO THE EXTERNAL ZONE OF THE MEDIAN-EMINENCE SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE DOUBLE LABELING; ENKEPHALIN; FLUORESCENCE MICROSCOPY; HYPOTHALAMUS; IMMUNOCYTOCHEMISTRY; RETROGRADE LABELING; NEUROENDOCRINOLOGY; PEPTIDES; PITUITARY ID IMMUNO-CYTOCHEMICAL LOCALIZATION; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; FLUORO-GOLD; GUINEA-PIG; RETROGRADE; CORTICOTROPIN; HYPOTHALAMUS; PEPTIDES; CRF AB The enkephalin-immunoreactive neurons that project to the external zone of the median eminence were identified on thin paraffin and thick vibratome sections using a combination of retrograde labeling with peripherally administered Fluoro-Gold and immunocytochemistry. The vast majority of the enkephalin-immunoreactive neurons that project to the external zone of the median eminence (ME) reside in the paraventricular nucleus (PVN) of the hypothalamus. Within the PVN, the majority of these hypophysiotropic neurons are located in the medial parvicellular subdivision, while a smaller number can be detected in the anterior and the periventricular subdivisions. Although many enkephalin-immunoreactive neurons are present in other hypophysiotropic areas of the hypothalamus, such as the medial preoptic area, the anterior periventricular area, and the arcuate nucleus, only a few of these can be retrogradely labeled from the ME. These results provide morphological evidence for the key role of paraventricular enkephalin-immunoreactive neurons in the regulation of neuroendocrine functions. RP MERCHENTHALER, I (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,FUNCT MORPHOL SECT,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 28 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 1 PY 1992 VL 326 IS 1 BP 112 EP 120 DI 10.1002/cne.903260110 PG 9 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA JY954 UT WOS:A1992JY95400009 PM 1479064 ER PT J AU LAMB, ME AF LAMB, ME TI FAMILY VIOLENCE IN CROSS-CULTURAL-PERSPECTIVE - LEVINSON,D SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Book Review RP LAMB, ME (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD DEC PY 1992 VL 23 IS 4 BP 535 EP 536 DI 10.1177/0022022192234010 PG 2 WC Psychology, Social SC Psychology GA JY216 UT WOS:A1992JY21600010 ER PT J AU ACCILI, D CAMA, A BARBETTI, F KADOWAKI, H KADOWAKI, T TAYLOR, SI AF ACCILI, D CAMA, A BARBETTI, F KADOWAKI, H KADOWAKI, T TAYLOR, SI TI INSULIN RESISTANCE DUE TO MUTATIONS OF THE INSULIN-RECEPTOR GENE - AN OVERVIEW SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Review DE INSULIN; INSULIN RESISTANCE; INSULIN RECEPTOR; GENE; DIABETES ID TYROSINE KINASE DOMAIN; CELL-SURFACE; ACANTHOSIS NIGRICANS; DIABETES-MELLITUS; IMPAIRS TRANSPORT; DECREASED LEVELS; MUTANT ALLELES; MESSENGER-RNA; ALPHA-SUBUNIT; PIMA-INDIANS C1 UNIV CHIETI,FAC MED & CHIRURG,CHIETI,ITALY. ASAHI LIFE RES FDN,TOKYO,JAPAN. IST SCI BIOMED S RAFFAELE,ROME,ITALY. UNIV TOKYO,SCH MED,DEPT INTERNAL MED 3,TOKYO 113,JAPAN. RP ACCILI, D (reprint author), NIDDK,DIABET BRANCH,BLDG 10,RM 8N244,BETHESDA,MD 20892, USA. NR 50 TC 25 Z9 25 U1 1 U2 2 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD DEC PY 1992 VL 15 IS 11 BP 857 EP 864 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KG658 UT WOS:A1992KG65800013 PM 1291599 ER PT J AU MARUTHAINAR, K PENGLOH, Y SMYTH, DG AF MARUTHAINAR, K PENGLOH, Y SMYTH, DG TI THE PROCESSING OF BETA-ENDORPHIN AND ALPHA-MELANOTROPHIN IN THE PARS-INTERMEDIA OF XENOPUS-LAEVIS IS INFLUENCED BY BACKGROUND ADAPTATION SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID NEUROINTERMEDIATE LOBE; PRO-OPIOMELANOCORTIN; COMMON PRECURSOR; PITUITARY-GLAND; INACTIVE FORMS; RAT PITUITARY; PEPTIDES; ACETYLATION; LIPOTROPIN; ANTERIOR AB Beta-Endorphin-and alpha-melanotrophin (alpha-MSH)-related peptides were extracted from the pars intermedia of Xenopus laevis maintained for 2, 4 or 6 weeks on a white background and for the same periods on a black background. The peptides were resolved under dissociating conditions by gel exclusion chromatography on Sephadex G-50 and they were detected by radioimmunoassay with antibodies to beta-endorphin, alpha,N-acetyl beta-endorphin and alpha-MSH. The beta-endorphin-related peptides separated into two fractions of different molecular size. Further purification of the peptides in each fraction was by ion exchange chromatography on SP-Sephadex C-25 and by high-pressure liquid chromatography. The a-MSH-related peptides were resolved by gel exclusion and ion exchange chromatography. The purified beta-endorphin- and alpha-MSH-immunoreactive peptides were identified by comparison of their chromatographic properties with the corresponding peptides from porcine pituitary or by comparison with synthetic peptides. The major form of beta-endorphin in the pars intermedia of the frog adapted to a white background was identified as alpha,N-acetyl beta-endorphin (1-8); it was accompanied by a small quantity of acetylated peptides with molecular size similar to beta-endorphin. In contrast, the pars intermedia of the frogs adapted to a black background contained approximately equal amounts of alpha,N-acetyl beta-endorphin (18) and the larger forms of beta-endorphin. The higher molecular weight forms were identified as the alpha,N-acetyl derivatives of beta-endorphin (1-26), (1-27) and (1-31); however after 6 weeks of white adaptation the sole remaining peptide in this group was the 26-residue peptide. An additional beta-endorphin immunoreactive peptide, provisionally identified as beta-endorphin (10-26), was present in both black- and white-adapted animals; the amounts of this peptide increased during white adaptation. Major differences in the processing of alpha-MSH were also observed. In the frogs adapted to a black background des-acetyl alpha-MSH greatly predominated over the acetyl form whereas after 6- weeks adaptation to a white background the acetylated peptide proved to be the principal component. The results demonstrate that the proteolytic processing of beta-endorphin and the acetylation of alpha-MSH in Xenopus laevis are influenced by background adaptation. The formation of beta-endorphin (1-8) appears to reflect the action of an endopeptidase that acts at the single arginine residue present at position 9. This cleavage does not appear to take place in mammalian beta-endorphins where position 9 is occupied by lysine. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. RP MARUTHAINAR, K (reprint author), NATL INST MED RES,PEPTIDE CHEM LAB,MILL HILL,LONDON NW7 1AA,ENGLAND. NR 28 TC 19 Z9 19 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD DEC PY 1992 VL 135 IS 3 BP 469 EP 478 DI 10.1677/joe.0.1350469 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KC276 UT WOS:A1992KC27600009 PM 1336791 ER PT J AU HAMMOND, SA BOLLINGER, RC STANHOPE, PE QUINN, TC SCHWARTZ, D CLEMENTS, ML SILICIANO, RF AF HAMMOND, SA BOLLINGER, RC STANHOPE, PE QUINN, TC SCHWARTZ, D CLEMENTS, ML SILICIANO, RF TI COMPARATIVE CLONAL ANALYSIS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1)-SPECIFIC CD4+ AND CD8+ CYTOLYTIC LYMPHOCYTES-T ISOLATED FROM SERONEGATIVE HUMANS IMMUNIZED WITH CANDIDATE HIV-1 VACCINES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ENVELOPE GENE; CELL CLONES; AIDS VIRUS; HTLV-III; GLYCOPROTEIN GP120; RECOMBINANT GP160; GENOMIC DIVERSITY; SOLUBLE-PROTEIN; ANTIGEN; REPLICATION AB The lysis of infected host cells by virus-specific cytolytic T lymphocytes (CTL) is an important factor in host resistance to viral infection. An optimal vaccine against human immunodeficiency virus type 1 (HIV-1) would elicit virus-specific CTL as well as neutralizing antibodies. The induction by a vaccine of HIV-1-specific CD8+ CTL in humans has not been previously reported. In this study, CTL responses were evaluated in HIV-1-seronegative human volunteers participating in a phase I acquired immune deficiency syndrome (AIDS) vaccine trial involving a novel vaccine regimen. Volunteers received an initial immunization with a live recombinant vaccinia virus vector carrying the HIV-1 env gene and a subsequent boost with purified env protein. An exceptionally strong env-specific CTL response was detected in one of two vaccine recipients, while modest but significant env-specific CTL activity was present in the second vaccinee. Cloning of the responding CTL gave both CD4+ and CD8+ env-specific CTL clones, permitting a detailed comparison of critical functional properties of these two types of CTL. In particular, the potential antiviral effects of these CTL were evaluated in an in vitro system involving HIV-1 infection of cultures of normal autologous CD4+ lymphoblasts. At extremely low effector-to-target ratios, vaccine-induced CD8 + CTL clones lysed productively infected cells present within these cultures. When tested for lytic activity against target cells expressing the HIV-1 env gene, CD8+ CTL were 3-10-fold more active on a per cell basis than CD4+ CTL. However, when tested against autologous CD4+ lymphoblasts acutely infected with HIV-1, CD4+ clones lysed a much higher fraction of the target cell population than did CD8+ CTL. CD4+ CTL were shown to recognize not only the infected cells within these acutely infected cultures but also noninfected CD4+ T cells that had passively taken up gp120 shed from infected cells and/or free virions. These results were confirmed in studies in which CD4+ lymphoblasts were exposed to recombinant gp120 and used as targets for gp120-specific CD4+ and CD8+ CTL clones. gp120-pulsed, noninfected targets were lysed in an antigen-specific fashion by CD4+ but not CD8+ CTL clones. Taken together, these observations demonstrate that in an in vitro HIV-1 infection, sufficient amounts of gp120 antigen are produced and shed by infected cells to enable uptake by cells that are not yet infected, resulting in the lysis of these noninfected cells by gp120-specific, CD4+ CTL. However, the antigen processing pathways involved in this reaction do not allow for association of gp120 peptides with class I molecules on the target cells. Thus, in contrast to CD4+ CTL, gp120-specific CD8+ CTL can correctly distinguish between productively infected cells and noninfected T cells that have acquired gp120 via CD4. With respect to the critical question of crossreactivity of vaccine-induced CTL on divergent strains of HIV-1, some vaccine-induced CD8+ CTL clones showed complete crossreactivity with targets expressing the env genes of the divergent MN and RF isolates. The implications of these findings for the development of HIV-1 vaccines and for the pathogenesis of AIDS are discussed. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV MOLEC & CLIN RHEUMATOL,1049 ROSS BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR IMMUNIZAT RES,BALTIMORE,MD 21205. RI Quinn, Thomas/A-2494-2010 FU NIAID NIH HHS [2U01 AI-2768, AI-28018, AI-322871] NR 70 TC 105 Z9 106 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1992 VL 176 IS 6 BP 1531 EP 1542 DI 10.1084/jem.176.6.1531 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KA481 UT WOS:A1992KA48100006 PM 1460417 ER PT J AU PETEN, EP STRIKER, LJ CAROME, MA ELLIOTT, SJ YANG, CW STRIKER, GE AF PETEN, EP STRIKER, LJ CAROME, MA ELLIOTT, SJ YANG, CW STRIKER, GE TI THE CONTRIBUTION OF INCREASED COLLAGEN-SYNTHESIS TO HUMAN GLOMERULOSCLEROSIS - A QUANTITATIVE-ANALYSIS OF ALPHA-2IV COLLAGEN MESSENGER-RNA EXPRESSION BY COMPETITIVE POLYMERASE CHAIN-REACTION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GROWTH-HORMONE; EXTRACELLULAR-MATRIX; IV COLLAGEN; LAMININ; KIDNEY AB We previously reported that one of the main components of the sclerotic material in human glomerular diseases was type IV collagen. In this study we examined the contribution of increased synthesis to this process at the gene expression level. Sufficient material has not been available to study type IV collagen synthesis by normal or sclerotic glomeruli in humans. We took advantage of the availability of nephrectomy specimens from patients with renal carcinoma, and of the observation that approximately 50% of these patients develop varying degrees of glomerulosclerosis. We microdissected glomeruli from 10 patients and analyzed them using in situ reverse transcription coupled with polymerase chain reaction (PCR) analyses (in situ RT-PCR). Alpha2IV collagen mRNA, after reverse transcription into cDNA, was detected in all patients and appeared to be increased in those with glomerulosclerosis (n = 5). A competitive PCR assay was developed to quantitate this change. There was an average 3.7-fold increase in glomerular type IV collagen cDNA in patients with significant sclerosis. This change was not due to an increased number of glomerular cells. Thus, glomerulosclerosis in humans is associated with an elevation of glomerular type IV collagen gene expression, suggesting that increased synthesis of type IV collagen may represent one component of this process. C1 NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,BLDG 10,RM 3N110,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DEPT MED,NEPHROL SERV,WASHINGTON,DC 20307. WALTER REED ARMY MED CTR,DEPT CLIN INVEST,WASHINGTON,DC 20307. NR 21 TC 78 Z9 81 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1992 VL 176 IS 6 BP 1571 EP 1576 DI 10.1084/jem.176.6.1571 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KA481 UT WOS:A1992KA48100010 PM 1281210 ER PT J AU CATIPOVIC, B DALPORTO, J MAGE, M JOHANSEN, TE SCHNECK, JP AF CATIPOVIC, B DALPORTO, J MAGE, M JOHANSEN, TE SCHNECK, JP TI MAJOR HISTOCOMPATIBILITY COMPLEX CONFORMATIONAL EPITOPES ARE PEPTIDE SPECIFIC SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS-I MOLECULES; TOXIC LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; MHC; ANTIGEN; BETA-2-MICROGLOBULIN; EXPRESSION; PROTEIN; GENES; CELLS AB Serologically distinct forms of H-2K(b) are stabilized by loading cells expressing "empty" class I major histocompatibility complex (MHC) molecules with different H-2K(b) binding peptides. The H-2K(b) epitope recognized by monoclonal antibody (mAb) 28.8.6 was stabilized by ovalbumin (OVA) (257-264) and murine cytomegalovirus (MCMV) pp89 (168-176) peptides, but not by vesicular stomatic virus nucleoprotein (VSV NP) (52-59) and influenza NP (Y345-360) peptides. The H-2K(b) epitope recognized by mAb 34.4.20 was stabilized by VSV NP (52-59) peptide but not by OVA (257-264), MCMV pp89 (168-176), or influenza NP (Y345-360) peptides. Immunoprecipitation of H-2K(b) molecules from normal cells showed that 28.8.6 and 34.4.20 epitopes were only present on a subset of all conformationally reactive H-2K(b) molecules. Using alanine-substituted derivatives of the VSV peptide, the 28.8.6 epitope was completely stabilized by substitution of the first residue and partially stabilized by substitution of the third or the fifth residues in the peptides. These results indicate that distinct conformational MHC epitopes are dependent on the specific peptide that occupies the antigenic peptide binding groove on individual MHC molecules. The changes in MHC epitopes observed may also be important in understanding the diversity of T cell receptors used in an immune response and the influence of peptides on development of the T cell repertoire. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CLIN IMMUNOL,BALTIMORE,MD 21205. NCI,DIV CANC BIOL & DIAG,BIOCHEM LAB,BETHESDA,MD 20892. NR 40 TC 116 Z9 116 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1992 VL 176 IS 6 BP 1611 EP 1618 DI 10.1084/jem.176.6.1611 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KA481 UT WOS:A1992KA48100015 PM 1281212 ER PT J AU KENNY, JJ MORATZ, CM GUELDE, G OCONNELL, CD GEORGE, J DELL, C PENNER, SJ WEBER, JS BERRY, J CLAFLIN, JL LONGO, DL AF KENNY, JJ MORATZ, CM GUELDE, G OCONNELL, CD GEORGE, J DELL, C PENNER, SJ WEBER, JS BERRY, J CLAFLIN, JL LONGO, DL TI ANTIGEN-BINDING AND IDIOTYPE ANALYSIS OF ANTIBODIES OBTAINED AFTER ELECTROPORATION OF HEAVY AND LIGHT CHAIN GENES ENCODING PHOSPHOCHOLINE-SPECIFIC ANTIBODIES - A MODEL FOR T15-IDIOTYPE DOMINANCE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNE-RESPONSE; TRANSGENIC MICE; MONOCLONAL-ANTIBODIES; MYELOMA PROTEINS; B-CELLS; PHOSPHORYLCHOLINE; DIVERSITY; DETERMINANT; SELECTION; SEQUENCES AB Antibodies bearing the T15 idiotype dominate the murine primary immune response to phosphocholine (PC). Analysis of antigen binding of antibodies derived from V1:DFL16.1:J(H)1 (V(H)1) germline and N region-derived variant heavy (H) chains and kappa22, kappa24, and kappa8 light (L) chains demonstrates that the T15H:kappa22L (T15) antibody binds PC at least 20-40 times better than other antibodies derived from alternate germline forms of the V(H)1 H chain and kappa22, kappa24, or kappa8 L chains. To achieve affinities in the same range as the T15 antibody, kappa24 and kappa8 L chain-containing antibodies must have H chains derived from variant N region or somatically mutated V(H)1 genes. Single amino acid differences at the VD junction of the various germline and N region variant V(H)1 H chains dictate the L chain that can associate with the H chain to produce a PC-specific antibody. Several H:L combinations give rise to T15 or M167 idiotype-positive antibodies that lack specificity for PC, and single amino acid substitutions or insertions at the V(H)1:D junction result in the loss of T15 or M167 idiotopes. Based on these observations, our data support a molecular model involving both preferential gene rearrangement and antigen-driven B cell selection to explain T15 idiotype dominance in the immune response to PC. In the absence of N region diversification, large numbers of neonatal B cells bearing the T15H:kappa22L surface immunoglobulin M (sIgM) receptors would be selected and expanded by autologous or environmental PC antigen into the long-lived peripheral B cell pool. C1 UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP KENNY, JJ (reprint author), NCI,FCRDC,DYNCORP,PROGRAM RESOURCES INC,POB B,BLDG 567,ROOM 227,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102]; NIAID NIH HHS [AI-12533] NR 37 TC 31 Z9 31 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1992 VL 176 IS 6 BP 1637 EP 1643 DI 10.1084/jem.176.6.1637 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KA481 UT WOS:A1992KA48100019 PM 1460422 ER PT J AU CORR, M BOYD, LF FRANKEL, SR KOZLOWSKI, S PADLAN, EA MARGULIES, DH AF CORR, M BOYD, LF FRANKEL, SR KOZLOWSKI, S PADLAN, EA MARGULIES, DH TI ENDOGENOUS PEPTIDES OF A SOLUBLE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE, H-2L(D)(S) - SEQUENCE MOTIF, QUANTITATIVE BINDING, AND MOLECULAR MODELING OF THE COMPLEX SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SURFACE-PLASMON RESONANCE; AMINO-ACID-SEQUENCE; T-CELL RECOGNITION; BIOSPECIFIC INTERACTION ANALYSIS; DOSE-RESPONSE CURVES; RADIOLIGAND ASSAY; SIGMOIDAL CURVES; ANTIGENIC SITES; LYMPHOCYTES-T; GENE AB To gain insight into the rules that govern the binding of endogenous and viral peptides to a given major histocompatibility complex (MHC) class I molecule, we characterized the amino acid sequences of a set of self peptides bound by a soluble analogue of murine H-2L(d), H-2L(d)s. We tested corresponding synthetic peptides quantitatively for binding in several different assays, and built three-dimensional computer models of eight peptide/H-2L(d)s complexes, based on the crystallographic structure of the human HLA-B27/peptide complex. Comparison of primary and tertiary structures of bound self and antigenic peptides revealed that residues 2 and 9 were not only restricted in sequence and tolerant of conservative substitutions, but were spatially constrained in the three-dimensional models. The degree of sequence variability of specific residues in MHC-restricted peptides reflected the lack of structural constraint on those amino acids. Thus, amino acid residues that define a peptide motif represent side chains required or preferred for a close fit with the MHC class I heavy chain. C1 NIAID,IMMUNOL LAB,MOLEC BIOL SECT,BLDG 10,RM 11N311,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 82 TC 159 Z9 159 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1992 VL 176 IS 6 BP 1681 EP 1692 DI 10.1084/jem.176.6.1681 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KA481 UT WOS:A1992KA48100024 PM 1281216 ER PT J AU COHN, DA SILVER, DH COWAN, CP COWAN, PA PEARSON, J AF COHN, DA SILVER, DH COWAN, CP COWAN, PA PEARSON, J TI WORKING MODELS OF CHILDHOOD ATTACHMENT AND COUPLE RELATIONSHIPS SO JOURNAL OF FAMILY ISSUES LA English DT Article ID REPRESENTATIONS AB Previous research has documented connections between adults' working models of childhood attachment relationships and the quality of parent-child relationships, but less attention has been devoted to examining such links for intimate adult relationships. Twenty-seven married couples were given George, Kaplan, and Main's Adult Attachment Interview and each person was rated as either secure or insecure with respect to attachment. Self-report measures of satisfaction with couple communication and marital relations and laboratory observations of couple interactions were collected. Results showed that self-reported marital satisfaction was not related to adult attachment classifications for either husbands or wives. However, observational ratings of couple interaction yielded differences for husbands. As compared to husbands classified as insecure, secure husbands were likely to be in better-functioning couples who engaged in more positive and fewer conflictual behaviors. In addition, couples' joint attachment classifications were related to observed couple behavior. Insecure-secure and secure-secure dyads did not differ, but both groups showed less conflict and were rated as better functioning than were insecure-insecure dyads. These findings suggest that a secure partner may buffer the negative effects of insecure attachment on the marital relationship. C1 NIMH,BETHESDA,MD 20892. UNIV CALIF BERKELEY,BERKELEY,CA 94720. RP COHN, DA (reprint author), UNIV VIRGINIA,DEPT PSYCHOL,GILMER HALL,CHARLOTTESVILLE,VA 22903, USA. NR 37 TC 101 Z9 103 U1 1 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0192-513X J9 J FAM ISSUES JI J. Fam. Issues PD DEC PY 1992 VL 13 IS 4 BP 432 EP 449 DI 10.1177/019251392013004003 PG 18 WC Family Studies SC Family Studies GA JY215 UT WOS:A1992JY21500002 ER PT J AU RACE, RE ERNST, D AF RACE, RE ERNST, D TI DETECTION OF PROTEINASE K-RESISTANT PRION PROTEIN AND INFECTIVITY IN MOUSE SPLEEN BY 2 WEEKS AFTER SCRAPIE AGENT INOCULATION SO JOURNAL OF GENERAL VIROLOGY LA English DT Note ID FIBRILS; INACTIVATION; IRRADIATION AB The sequential accumulation of the protease-resistant form of the endogenous prion protein (PrP-res) was compared to levels of scrapie infectivity in the spleen and brain of scrapie-infected mice at various times after inoculation. In mouse spleen PrP-res was detected 1 week after inoculation, and increased 65-fold between 1 and 3 weeks post-inoculation and an additional 15-fold during the next 17 weeks. Infectivity in spleen reached a maximum plateau level by 3 weeks. In contrast, in mouse brain PrP-res was not detected until 8 weeks after inoculation and then increased 200-fold during the next 12 weeks. During this same time, infectivity increased approximately 10000-fold. Therefore, in both spleen and brain of scrapie-infected mice accumulation of PrP-res and infectivity appear to be associated. However, it was not possible to show quantitative correlations between PrP-res detection and infectivity, perhaps owing to the inaccuracy of the infectivity assay. RP RACE, RE (reprint author), NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 15 TC 43 Z9 44 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 1992 VL 73 BP 3319 EP 3323 DI 10.1099/0022-1317-73-12-3319 PN 12 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA KD372 UT WOS:A1992KD37200037 PM 1361522 ER PT J AU ABE, R FOOPHILLIPS, M GRANGER, LG KANAGAWA, O AF ABE, R FOOPHILLIPS, M GRANGER, LG KANAGAWA, O TI CHARACTERIZATION OF THE MLS(F) SYSTEM .1. A NOVEL POLYMORPHISM OF ENDOGENOUS SUPERANTIGENS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; MAMMARY-TUMOR VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; MHC GENE-PRODUCTS; CLONAL DELETION; I-E; MONOCLONAL-ANTIBODIES; SELF-ANTIGENS; TOLERANCE; EXPRESSION AB In addition to Mls(a) (Mls-1a) and Mls(c) (Mls-2a, Mls-3a), we and others have recently described a third set of stimulatory minor lymphocyte stimulating (Mls) determinants, which are ligands for "I-E related" Vbeta, Vbeta5, Vbeta11, and Vbeta12. Although all Vbeta associated with the recognition of the conventional Mls determinants are, in general, uniformly deleted in those animals expressing relevant Mls, expression of Mls(f)-related Vbeta reveals various deletion patterns among different strains. Here we describe extensive genetic studies to evaluate the relationship among the self-Ag responsible for clonal deletion of T cells bearing Mls(f)-related Vbeta by using antibodies specific for TCR Vbeta chain. In addition, a panel of T cell clones specific for the Mls(f) determinant were generated and employed to analyze the determinant specificity, which is recognized by Mls(f)-reactive T cells in vitro as well as the role of class II molecules in T cell recognition of the Mls(f) determinants. The results of these two independent approaches provide evidence that the Mls(f) system is composed of a set of gene products that reveal a unique polymorphism in the induction of clonal deletion in vivo and in T cell activation in vitro. One of these gene products causes almost complete deletion of the self-Mls(f) reactive T cell repertoire in vivo and elicits a strong proliferative response to Mls(f)-specific T cell clones. Expression of the other gene products results in the clonal deletion of only part of the Mls(f)-reactive T cell repertoire. Furthermore, the response pattern of Mls(f)-specific clones to intra-MHC recombinant inbred strains and the inhibition pattern of these clones by anti-class II antibody suggested that although expression of the I-E molecule is essential for T cell recognition of Mls(f) determinants, the Abeta gene may also contribute to the efficient presentation of Mls(f) determinants by forming unique class II EalphaAbeta molecules. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP ABE, R (reprint author), USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,MAIL STOP 44,BETHESDA,MD 20889, USA. FU NIAID NIH HHS [AI30803] NR 42 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1992 VL 149 IS 11 BP 3429 EP 3439 PG 11 WC Immunology SC Immunology GA JY875 UT WOS:A1992JY87500001 PM 1331235 ER PT J AU FOOPHILLIPS, M KOZAK, CA PRINCIPATO, MAC ABE, R AF FOOPHILLIPS, M KOZAK, CA PRINCIPATO, MAC ABE, R TI CHARACTERIZATION OF THE MLS(F) SYSTEM .2. IDENTIFICATION OF MOUSE MAMMARY-TUMOR VIRUS PROVIRUSES INVOLVED IN THE CLONAL DELETION OF SELF-MLS(F)-REACTIVE T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SUPERANTIGEN; ANTIGENS; GENES; EXPRESSION; V-BETA-11; TOLERANCE; PRODUCTS; MICE AB The genetic linkage of loci encoding stimulatory Mls(s) and Mls(c) determinants with proviruses of mouse mammary tumour viruses (MMTV) has been shown. We previously have reported that the ligand(s) for Vbeta5, Vbeta11, and Vbeta12 behaves as a novel minor lymphocyte-stimulating (Mls) determinant(s), Mls(f), to induce the strong proliferation of unprimed T cells, and that this ligand(s) also functions as a self-Ag for the clonal deletion of self-reactive T cells. In the accompanying paper (Part I), a unique polymorphism characteristic of the Mls(f) gene product is presented. In order to determine the genetic basis for this novel Mls system, we examined the progeny of multiple genetic crosses to identify the MMTV proviral loci involved in the clonal deletion of self-Mls(f)-reactive T cells. Results from these investigations indicated that at least three known MMTV proviruses, Mtv-8, Mtv-9, and Mtv-11 are involved in the expression of Mls(f) gene products. Presence of Mtv-9 results in the complete deletion of Vbeta5, Vbeta11, and Vbeta12; Mtv-8 is associated with the complete deletion of Vbeta12, but only a partial deletion of Vbeta11 (primarily CD4-positive T cell subset) with little or no deletion of Vbeta5; and Mtv-11 induces the complete deletion of Vbeta11 and Vbeta12, but no deletion of Vbeta5. Given the significant sequence homology in the C-terminal portion of the open reading frame (ORF) region among these three MMTV and the almost equivalent effect of these three MMTV provirus upon the Vbeta12 repertoire, their apparent hierarchic effect upon the Vbeta5 and Vbeta11 repertoires suggests that affinity differences in recognition of the same determinant by different TCR Vbeta may play a significant role in the clonal deletion of self-reactive T cells. C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,MAIL STOP 44,BETHESDA,MD 20889. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. US FDA,DIV MICROBIOL,VIRULENCE ASSESSMENT BRANCH,LAUREL,MD 20708. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 27 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1992 VL 149 IS 11 BP 3440 EP 3447 PG 8 WC Immunology SC Immunology GA JY875 UT WOS:A1992JY87500002 PM 1331236 ER PT J AU REDEGELD, FA CHATTERJEE, S BERGER, NA SITKOVSKY, MV AF REDEGELD, FA CHATTERJEE, S BERGER, NA SITKOVSKY, MV TI POLY-(ADP-RIBOSE) POLYMERASE PARTIALLY CONTRIBUTES TO TARGET-CELL DEATH TRIGGERED BY CYTOLYTIC LYMPHOCYTES-T SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NONDIVIDING HUMAN-LYMPHOCYTES; NUCLEAR ADP-RIBOSYLATION; TUMOR-NECROSIS-FACTOR; DNA STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE; 2-CHLORODEOXYADENOSINE TOXICITY; INHIBITORS; DAMAGE; SYNTHETASE; MECHANISM AB We hypothesized that CTL-induced target cell (TC) death is partially due to processes that follow the DNA damage in target cells and include the activation of poly-ADP-ribose transferase (PADPRT) by DNA strand breaks. According to this model, the activated PADPRT is expected to deplete NAD, ATP, and to contribute to the TC death. We used inhibitors of PADPRT and a PADPRT-deficient cell mutant, as well as other nucleated TC and SRBC to test the role of PADPRT in CTL-induced cytotoxicity. It is found that inhibitors of PADPRT (3-aminobenzamide, benzamide (aromatic amides)) and nicotinamide all inhibit the CTL-mediated lysis of both Ag-specific TC and of Ag-nonbearing TC. The effect of PADPRT inhibitors was not due to inhibition of the lethal hit delivery by CTL, because in parallel control experiments, the same inhibitors did not interfere with CTL-induced lysis of SRBC, cells that are devoid of nuclei and PADPRT. Moreover, the effect of inhibitors of PADPRT did not affect earlier stages of lethal hit delivery because 3-aminobenzamide and benzamide did not interfere with CTL-induced DNA fragmentation in TC at concentration which protected TC lysis. Importantly, a PADPRT-deficient cell line was also much more resistant to CTL-induced lysis as tested in retargeting (4 and 8 h) assays; this was expected if activation of PADPRT is indeed involved in TC death. Control experiments reveal that the relative resistancy of the PADPRT-deficient cell mutant to CTL-induced lysis was not related to its impaired ability to form conjugates and to trigger CTL (as tested in granule exocytosis assay). In addition, PADPRT-deficient cells were as susceptible to CTL-induced DNA fragmentation as were the control cells; yet, they were resistant to CTL-induced Cr-51-release. Control cells and PADPRT-deficient mutant were equally susceptible to antibody + C'-mediated lysis. Our data support the view that the activation of PADPRT can contribute to the CTL-induced cytolysis of some TC, but is not involved in lysis of other TC, as evidenced by the ability of CTL to efficiently lyse SRBC. These data suggest that there could be multiple molecular pathways of TC death in CTL-mediated cytotoxicity and the relative contribution of PADPRT and/or other enzymes will reflect the individual make-up of a particular TC. C1 NIAID,IMMUNOL LAB,9000 ROCKVILLE PIKE,BLDG 10,RM 11N311,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,IRELAND CANC CTR,DEPT MED & BIOCHEM,DIV HEMATOL ONCOL,CLEVELAND,OH 44106. RI Redegeld, Frank/O-6534-2016 OI Redegeld, Frank/0000-0001-8830-7960 NR 50 TC 23 Z9 23 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1992 VL 149 IS 11 BP 3509 EP 3516 PG 8 WC Immunology SC Immunology GA JY875 UT WOS:A1992JY87500012 PM 1431121 ER PT J AU SIMEK, SL FIELDS, AP COLBURN, NH WINKLERPICKETT, R YOUNG, HA AF SIMEK, SL FIELDS, AP COLBURN, NH WINKLERPICKETT, R YOUNG, HA TI THE PRESENCE IN A MOUSE T-CELL LINE OF A 97-KDA PROTEIN-KINASE-C (PKC) WITH CHARACTERISTICS SIMILAR TO KNOWN MEMBERS OF THE NOVEL PKC SUBGROUP AND ITS POSSIBLE ROLE IN LYMPHOCYTE GENE-EXPRESSION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PHORBOL-MYRISTATE ACETATE; GAMMA GENOMIC DNA; INTERFERON-GAMMA; ESTER RECEPTOR; RAT-BRAIN; ACTIVATION; BETA; IDENTIFICATION; NITROCELLULOSE; TRANSLOCATION AB The receptor for tumor-promoting phorbol esters has been shown to be the Ca+2 /phospholipid dependent enzyme protein kinase C (PKC). There are two major groups of PKC, the conventional PKC isotypes (alpha, betaI, betaII, gamma) and the novel Ca+2-independent PKC (delta, epsilon, zeta, eta). Phorbol esters previously have been demonstrated to increase human IFN-gamma gene expression after treatment of a murine T cell line (Cl 9) that has been transfected with human IFN-gamma genomic DNA. In contrast, treatment with Ca+2 ionophore alone or in combination with phorbol ester did not enhance IFN-gamma production in a synergistic manner above the level obtained with phorbol ester treatment alone. To determine whether the lack of effect of Ca+2 ionophore is due to a defect in PKC, we compared the level of PKC autophosphorylation in the mouse T cell line (Cl 9), a mouse epidermal cell line (JB6), and purified rat brain PKC by in vitro kinase assays. The results demonstrate that instead of the expected 80-kDa autophosphorylated PKC band seen in purified rat brain PKC or mouse JB6 cell lysates, only a novel 97-kDa Ca+2-independent phosphoprotein was observed in Cl 9 cells. To ascertain if there was any nucleic acid sequence similarity to PKCepsilon, we hybridized Cl 9 poly(A+) RNA with a cloned fragment of the PKCepsilon gene and observed two hybridizing RNA bands (4.4 and 4.0 kb). Our results suggest that the 97-kDa phosphoprotein is similar to, but not identical with, PKCepsilon and is the major PKC expressed in the Cl 9 murine T cell line. These data suggested that the 97-kDa PKC may be responsible for the induction of both the transfected human IFN-gamma gene and the endogenous murine IL-2R alpha-chain. C1 NCI,FCRDC,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHARMACOL,CLEVELAND,OH 44106. NCI,FCRDC,DCT,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 39 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1992 VL 149 IS 11 BP 3542 EP 3549 PG 8 WC Immunology SC Immunology GA JY875 UT WOS:A1992JY87500016 PM 1431124 ER PT J AU PARKER, KC BEDNAREK, MA HULL, LK UTZ, U CUNNINGHAM, B ZWEERINK, HJ BIDDISON, WE COLIGAN, JE AF PARKER, KC BEDNAREK, MA HULL, LK UTZ, U CUNNINGHAM, B ZWEERINK, HJ BIDDISON, WE COLIGAN, JE TI SEQUENCE MOTIFS IMPORTANT FOR PEPTIDE BINDING TO THE HUMAN MHC CLASS-I MOLECULE, HLA-A2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; SYNTHETIC PEPTIDES; MATRIX PROTEIN; VIRAL PEPTIDE; RECOGNITION; CELLS; IDENTIFICATION; STABILITY; ANTIGENS; EPITOPES AB Previous studies have indicated that most HLA-A2-binding peptides are 9 amino acid (aa) residues long, with a Leu at position 2 (P2), and a Val or Leu at P9. We compared the binding properties of different peptides by measuring the rate of dissociation of beta2-microglobulin from peptide-specific HLA-A2 complexes. The simplest peptide that we identified that could form HLA-A2 complexes had the sequence (in single letter aa code) GLFGGGGGV, indicating that three nonglycine aa are sufficient for binding to HLA-A2. To determine whether most nonapeptides that contained Leu at P2 and Val or Leu at P9 could bind to HLA-A2, we tested the binding of nonapeptides selected from published HIV and melanoma protein sequences, and found that six of seven tested formed stable HLA-A2 complexes. We identified an optimal antigenic undecapeptide from the cytomegalovirus gB protein that could form stable HLA-A2 complexes that contained apparent anchor residues at P2 and P11 (sequence FIAGNSAYEYV), indicating that the spacing between anchor residues can be somewhat variable. Finally, we tested the importance of every aa in the influenza A matrix peptide 58-66 (sequence GILGFVFTL) for binding to HLA-A2, by using Ala-substituted and Lys-substituted peptides. We found that multiple positions were important for stable binding, including P2, P3, P5-P7, and P9. We conclude that the P2 and P9 anchor residues are of prime importance for peptide binding to HLA-A2. However, other peptide side chains (especially at P3) contribute to the stability of the interaction. In certain cases, the optimal length for peptide binding can be longer than 9 residues. C1 NINCDS,NEUROIMMUNOL BRANCH,MERCK SHARP & DOHME RES LABS,BETHESDA,MD 20892. RP PARKER, KC (reprint author), NIAID,BIOL RESOURCES BRANCH,BLDG 4,RM 413,BETHESDA,MD 20892, USA. OI Parker, Kenneth/0000-0002-6282-2478 NR 38 TC 216 Z9 218 U1 1 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 DEC 1 PY 1992 VL 149 IS 11 BP 3580 EP 3587 PG 8 WC Immunology SC Immunology GA JY875 UT WOS:A1992JY87500022 PM 1331239 ER PT J AU BIANCHINE, PJ BURD, PR METCALFE, DD AF BIANCHINE, PJ BURD, PR METCALFE, DD TI IL-3-DEPENDENT MAST-CELLS ATTACH TO PLATE-BOUND VITRONECTIN - DEMONSTRATION OF AUGMENTED PROLIFERATION IN RESPONSE TO SIGNALS TRANSDUCED VIA CELL-SURFACE VITRONECTIN RECEPTORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AMINO-ACID SEQUENCE; GROWTH-FACTOR; T-CELLS; INOSITOL PHOSPHATES; ALPHA-V; FIBRONECTIN; ACTIVATION; DIFFERENTIATION; ADHESION; COMPLEX AB The adhesive interactions of activated mast cells with the extracellular matrix play an important role in anchorage and cellular motility. In this report we demonstrate that IL-3-dependent bone marrow-derived mast cells adhere to plate-bound vitronectin with high affinity in a saturable and dose-dependent manner. This adhesion interaction is unique in that it does not require prior mast cell activation through FcepsilonRI or after treatment with PMA. It is inhibited by divalent cation chelation and by competitive inhibition with a synthetic Arginine-Glycine-Aspartate-Serine tetrapeptide. Polyclonal antisera for alpha(v)beta3, an integrin known to bind vitronectin, inhibits attachment to plate-bound vitronectin in a dose-dependent manner. Comparison of the adhesion interactions for vitronectin, fibronectin, and laminin indicate that adhesion to vitronectin is greater than that seen with either fibronectin or laminin, either in the presence or absence of PMA. FACS analysis using a monoclonal hamster anti-murine vitronectin receptor (alpha(v)) antibody followed by a fluorescein-conjugated rabbit anti-hamster IgG revealed no change in surface vitronectin receptor expression after FcepsilonRI-mediated cell activation. Proliferation assays with correction for cell viability revealed a 25% increase in cell number above the maximal IL-3 response over a 24-h period of adhesion to a vitronectin-coated surface and a 41% increase over 96 h of adhesion to vitronectin. Binding to plate-bound vitronectin was not able to sustain cell viability in the absence of IL-3. Thus, IL-3-dependent bone marrow-derived mast cells adhere to vitronectin, an extracellular matrix protein present throughout connective tissues. This interaction generates a signal that results in the augmentation of the maximal IL-3-dependent mast cell proliferative response, thus demonstrating at least one way in which the interaction between mast cells and extracellular matrix alter the biologic responsiveness of the mast cell. RP BIANCHINE, PJ (reprint author), NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BLDG 10,ROOM 11C210,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 63 Z9 63 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1992 VL 149 IS 11 BP 3665 EP 3671 PG 7 WC Immunology SC Immunology GA JY875 UT WOS:A1992JY87500034 PM 1385529 ER PT J AU BARILLARI, G BUONAGURO, L FIORELLI, V HOFFMAN, J MICHAELS, F GALLO, RC ENSOLI, B AF BARILLARI, G BUONAGURO, L FIORELLI, V HOFFMAN, J MICHAELS, F GALLO, RC ENSOLI, B TI EFFECTS OF CYTOKINES FROM ACTIVATED IMMUNE CELLS ON VASCULAR CELL-GROWTH AND HIV-1 GENE-EXPRESSION - IMPLICATIONS FOR AIDS-KAPOSIS SARCOMA PATHOGENESIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACQUIRED IMMUNODEFICIENCY SYNDROME; YOUNG HOMOSEXUAL MEN; INFECTED T-CELLS; FACTOR-ALPHA; DEFICIENCY SYNDROME; TAT PROTEIN; INVIVO ACTIVATION; ENDOTHELIAL-CELLS; HTLV-III AB Kaposi's sarcoma (KS) arises more frequently in homosexual and bisexual men than in other groups of HIV-1 infected individuals. Clinico-epidemiologic data indicate that homosexuals often are infected with multiple microbial agents and/or subjected to other antigenic stimuli, preceding or accompanying HIV-1 infection. Signs of immune activation, in fact, frequently have been detected in these individuals, and the onset of KS can precede any sign of immunodeficiency. These data have suggested that products from activated immune cells may affect the development of AIDS-KS. Here we report that conditioned media from activated or dysregulated T cells contain a variety of cytokines that promote the growth of spindle cells derived from KS lesions of AIDS patients (AIDS-KS cells) and induce normal vascular cells, potential cell progenitors of the AIDS-KS cells, to acquire features of the KS cell phenotype ("spindle" cell morphology and growth responsiveness to the mitogenic effect of extracellular HIV-1 Tat protein). The same conditioned media or cytokines promote HIV-1 gene expression and rescue defective HIV-1 proviruses, interrupting HIV-1 latency and increasing Tat production. The cellular and viral effects of cytokines are increased in an additive or synergistic manner by picomolar concentrations of extracellular Tat. These data suggest that cytokines produced by activated immune cells cooperate with HIV-1 infection in AIDS-KS pathogenesis. C1 NCI,TUMOR CELL BIOL LAB,BLDG 37,RM 6A09,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. BIOTECH RES LABS INC,GAITHERSBURG,MD 20877. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 74 TC 195 Z9 196 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 DEC 1 PY 1992 VL 149 IS 11 BP 3727 EP 3734 PG 8 WC Immunology SC Immunology GA JY875 UT WOS:A1992JY87500043 PM 1431144 ER PT J AU GALLANT, JE MOORE, RD RICHMAN, DD KERULY, J CHAISSON, RE BARTLETT, J MCAVINUE, S BRYSON, Y COHEN, H FISCHL, M BOLIN, T KESSLER, H BURROUGH, Y MILDVAN, D FOX, A RICHMAN, D FREEMAN, B SIMON, G GRABOWY, KW CHERNOFF, D DUFF, P THOMPSON, S BARRETT, K AWE, R CHAPMAN, R LEONARD, S BAINES, L TURNER, P HAWKINS, M MURRAY, H BOWERS, J LANE, C TILSON, H ANDREWS, E SMILEY, L AF GALLANT, JE MOORE, RD RICHMAN, DD KERULY, J CHAISSON, RE BARTLETT, J MCAVINUE, S BRYSON, Y COHEN, H FISCHL, M BOLIN, T KESSLER, H BURROUGH, Y MILDVAN, D FOX, A RICHMAN, D FREEMAN, B SIMON, G GRABOWY, KW CHERNOFF, D DUFF, P THOMPSON, S BARRETT, K AWE, R CHAPMAN, R LEONARD, S BAINES, L TURNER, P HAWKINS, M MURRAY, H BOWERS, J LANE, C TILSON, H ANDREWS, E SMILEY, L TI INCIDENCE AND NATURAL-HISTORY OF CYTOMEGALOVIRUS DISEASE IN PATIENTS WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE TREATED WITH ZIDOVUDINE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; AIDS; INFECTION; EFFICACY; SAFETY; TRIAL AB Data were analyzed from a multicenter observational cohort study of 1002 persons with AIDS or AIDS-related complex (ARC) and total CD4 cell count <0.25 x 10(9)/L treated with zidovudine between April 1987 and April 1988. Cytomegalovirus (CMV) disease developed in 109 patients (10.9%), with a 2-year actuarial risk of 15%. Manifestations included retinitis (93 patients), esophagitis (10), colitis (8), gastritis (1), hepatitis (1), and encephalitis (1). The probability of CMV disease at 2 years for patients with initial counts <0. 1 x 10(9)/L was 21.4%, compared with 10.3% for patients with initial counts greater-than-or-equal-to 0.1 x 10(9)/L (P < .001). By proportional hazards analysis, baseline CD4 cell count <0.1 x 10(9)/L, enrollment diagnosis of AIDS, and homosexuality were significantly associated with subsequently developing CMV disease. Median survival after diagnosis of CMV disease was 173 days, and CMV was an independent predictor of death. CMV contributes to AIDS-related morbidity and mortality. As new anti-CMV drugs become available, prophylaxis should be targeted at individuals with CD4 cell counts <0. 1 x 10(9)/L. C1 VET ADM MED CTR,DEPT PATHOL,SAN DIEGO,CA. VET ADM MED CTR,DEPT MED,SAN DIEGO,CA. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV MIAMI,CORAL GABLES,FL 33124. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. BETH ISRAEL MED CTR,NEW YORK,NY 10003. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. EMORY UNIV,ATLANTA,GA 30322. JOHNSON GEN HOSP,HOUSTON,TX. KAISER PERMANENTE MED GRP,LOS ANGELES,CA. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. NIAID,BETHESDA,MD 20892. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. RP GALLANT, JE (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MED,AIDS SERV,1830 E MONUMENT ST,SUITE 7400,BALTIMORE,MD 21205, USA. NR 24 TC 455 Z9 464 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1992 VL 166 IS 6 BP 1223 EP 1227 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JZ581 UT WOS:A1992JZ58100003 PM 1358986 ER PT J AU MCKENZIE, R KOTWAL, GJ MOSS, B HAMMER, CH FRANK, MM AF MCKENZIE, R KOTWAL, GJ MOSS, B HAMMER, CH FRANK, MM TI REGULATION OF COMPLEMENT ACTIVITY BY VACCINIA VIRUS COMPLEMENT-CONTROL PROTEIN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HERPES-SIMPLEX VIRUS-1; GLYCOPROTEIN-C; 3RD COMPONENT; GUINEA-PIG; C3B; NEUTRALIZATION; RECEPTOR; CASCADE; CELLS AB A major protein secreted by vaccinia virus-infected cells has structural similarity to the super-family of complement-control proteins. This vaccinia complement-control protein (VCP) was studied to determine how it regulates complement activation. VCP was bound by C4b and C3b and served as a cofactor with factor I in cleaving these two molecules. VCP inhibited the formation and accelerated the decay of the classical C3 convertase. It also accelerated decay of the alternative pathway convertase. although higher concentrations were apparently needed. In vitro, therefore, VCP interfered with the classical and alternative complement pathways at several steps. In vivo, this interference may increase the virulence of vaccinia virus by enabling it to escape attack by the host's complement system. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP MCKENZIE, R (reprint author), NIAID,CLIN INVEST LAB,BLDG 10,ROOM 11N228,BETHESDA,MD 20892, USA. NR 20 TC 121 Z9 122 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1992 VL 166 IS 6 BP 1245 EP 1250 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JZ581 UT WOS:A1992JZ58100006 PM 1431243 ER PT J AU WARD, RL CLEMENS, JD KNOWLTON, DR RAO, MR VANLOON, FPL HUDA, N AHMED, F SCHIFF, GM SACK, DA AF WARD, RL CLEMENS, JD KNOWLTON, DR RAO, MR VANLOON, FPL HUDA, N AHMED, F SCHIFF, GM SACK, DA TI EVIDENCE THAT PROTECTION AGAINST ROTAVIRUS DIARRHEA AFTER NATURAL INFECTION IS NOT DEPENDENT ON SEROTYPE-SPECIFIC NEUTRALIZING ANTIBODY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ORAL CHOLERA VACCINES; CYTOTOXIC LYMPHOCYTES-T; BOVINE ROTAVIRUS; FIELD TRIAL; GNOTOBIOTIC CALVES; YOUNG-CHILDREN; ANTIGENIC RELATIONSHIPS; VENEZUELAN INFANTS; NEONATAL CHALLENGE; CROSS-PROTECTION AB This case-control study sought to determine whether protection against clinically significant rotavirus diarrhea in children aged 4-35 months correlated with titers of serum neutralizing antibody and, if so, whether this protection was serotype-specific. Titers of acute-phase sera from 156 cases of treated rotavirus diarrhea in rural Bangladesh were contrasted with titers from 312 contemporaneously selected, age-matched controls. Analyses of the culture-adapted rotaviruses from the cases revealed that 24%, 15%, 43%, and 17% belonged to serotypes 1-4, respectively. Titers of both homologous and heterologous neutralizing antibody in acute blood specimens of cases were significantly lower than those of matched controls. However, multivariate logistic regression models demonstrated that only antibody titers to heterotypic rotaviruses were independently associated with protection against rotavirus disease. These data, which indicate that the correlation of protection with neutralizing antibody titers is not serotype-specific, suggest that immunity to rotavirus disease may be mediated by other factors. C1 JOHNS HOPKINS SCH PUBL HLTH, BALTIMORE, MD USA. INT CTR DIARRHOEAL DIS RES, BANGLADESH, BANGLADESH. NICHHD, DIV EPIDEMIOL STAT, BETHESDA, MD 20892 USA. NICHHD, DIV PREVENT RES, BETHESDA, MD 20892 USA. RP WARD, RL (reprint author), JN GAMBLE INST MED RES, DIV CLIN VIROL, 2141 AUBURN AVE, CINCINNATI, OH 45219 USA. NR 57 TC 63 Z9 66 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1992 VL 166 IS 6 BP 1251 EP 1257 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JZ581 UT WOS:A1992JZ58100007 PM 1331249 ER PT J AU TROLLFORS, B LAGERGARD, T CLAESSON, BA THORNBERG, E MARTINELL, J SCHNEERSON, R AF TROLLFORS, B LAGERGARD, T CLAESSON, BA THORNBERG, E MARTINELL, J SCHNEERSON, R TI CHARACTERIZATION OF THE SERUM ANTIBODY-RESPONSE TO THE CAPSULAR POLYSACCHARIDE OF HAEMOPHILUS-INFLUENZAE TYPE-B IN CHILDREN WITH INVASIVE INFECTIONS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TOXOID CONJUGATE VACCINE; HEMOPHILUS-INFLUENZAE; GROUP-A; IMMUNOLOGICAL RESPONSES; ISOTYPE CONCENTRATIONS; SUBCLASS ANTIBODIES; OUTER-MEMBRANE; IGG SUBCLASSES; INFANTS; DISEASE AB The serum antibody response to the capsular polysaccharide of Haemophilus influenzae type b (Hib) was studied in 30 children aged 1 day-5 years with invasive Hib infections. From each child, serum was obtained 0-2 days, 5-11 days, 1 month, and 6-12 months after onset of symptoms. Total antibodies were determined with RIA and isotypes with ELISA. Only 2 children had antibody levels above the estimated protective level (0. 1 5 mug/mL) in the first serum sample. The antibody response was age dependent with wide individual variations. Children greater-than-or-equal-to 2 years had increases in IgG, IgM, and IgA antibodies with predominance of IgG. The initial IgG response was IgG1 and IgG2 with predominance of IgG1. In the last serum sample, IgG1 antibodies had decreased while IgG2 antibodies remained unchanged. Only 2 of 7 children < 1 year had a detectable antibody response. The correlation coefficient for total antibodies compared with the sum of IgG, IgM, and IgA was.88 (P < .0001) and for IgG compared with the sum of IgG1 and IgG2 was .97 (P < .0001). C1 GOTHENBURG UNIV,DEPT PEDIAT,S-41124 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT INFECT DIS,S-41124 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT PEDIAT ANAESTHESIA & INTENS CARE,S-41124 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT MED MICROBIOL & IMMUNOL,S-41124 GOTHENBURG,SWEDEN. NICHHD,DEV & MOLEC IMMUNITY LAB,BETHESDA,MD 20892. NR 33 TC 20 Z9 21 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1992 VL 166 IS 6 BP 1335 EP 1339 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JZ581 UT WOS:A1992JZ58100018 PM 1431250 ER PT J AU BORDEN, EC KIM, K RYAN, L BLUM, RH SHIRAKI, M TORMEY, DC COMIS, RL HAHN, RG PARKINSON, DR AF BORDEN, EC KIM, K RYAN, L BLUM, RH SHIRAKI, M TORMEY, DC COMIS, RL HAHN, RG PARKINSON, DR TI PHASE-II TRIALS OF INTERFERON-ALPHA AND INTERFERON-BETA IN ADVANCED SARCOMAS SO JOURNAL OF INTERFERON RESEARCH LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; ACTINOMYCIN-D; CYCLOPHOSPHAMIDE; ADRIAMYCIN AB Interferons (IFNs)-alpha and -beta were administered to patients with metastatic sarcomas in two different Eastern Cooperative Oncology Group studies. In one study, patients received IFN-alpha2b, 20 million units/m2 i.v. 5 days/week x 4, then 10 million units s.c. t.i.w. In the second study, patients received IFN-beta(ser) 180 million units t.i.w. Of 87 patients evaluable for response, there were three responses in 64 patients (5%) treated with IFN-alpha-2b and no responses in 23 patients treated with IFN-beta(ser). Severe or life-threatening fatigue with decline in performance status complicated treatment of 37% of patients receiving IFN-alpha2b and 17% of patients receiving IFN-beta(ser). Further investigation of IFNs in sarcomas should depend on evidence from preclinical studies demonstrating synergistic effects of IFNs combined with a cytoreductive modality which has proven activity in these malignancies. C1 UNIV WISCONSIN,CTR CLIN CANC,MADISON,WI 53792. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NYU MED CTR,NEW YORK,NY 10016. TUFTS UNIV,BOSTON,MA 02115. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NCI,BETHESDA,MD 20892. RP BORDEN, EC (reprint author), MED COLL WISCONSIN,CTR CANC,8701 WATERTOWN PLANK RD,MILWAUKEE,WI 53226, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA 21076, CA 16395, CA 23318] NR 11 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0197-8357 J9 J INTERFERON RES JI J. Interferon Res. PD DEC PY 1992 VL 12 IS 6 BP 455 EP 458 DI 10.1089/jir.1992.12.455 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KC716 UT WOS:A1992KC71600010 PM 1289413 ER PT J AU KORGE, BP COMPTON, JG STEINERT, PM MISCHKE, D AF KORGE, BP COMPTON, JG STEINERT, PM MISCHKE, D TI THE 2 SIZE ALLELES OF HUMAN KERATIN-1 ARE DUE TO A DELETION IN THE GLYCINE-RICH CARBOXYL-TERMINAL-V2 SUBDOMAIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID EPIDERMOLYSIS-BULLOSA SIMPLEX; INTERMEDIATE FILAMENTS; POLYMORPHIC KERATINS; EPIDERMAL KERATINS; POINT MUTATIONS; EXPRESSION; EVOLUTION; SEQUENCE; DOMAINS; INVITRO AB Two size variants of the type II human keratin 1 protein chain, termed 1a and 1b, have been described previously. Using amplification of genomic DNA by the polymerase chain reaction and sequence analysis we show here that the difference between these two alleles is due to a deletion of 21 bp in sequences encoding the V2 subdomain. This deletion corresponds to an entire glycine loop of seven amino acids. Pedigree analysis showed that the alleles are inherited as normal Mendelian traits. No additional alleles were detected in a survey of 88 alleles from 44 unrelated individuals, and the allelic frequency of 1a and 1b was 0.61 and 0.39. To determine the molecular basis of inherited dermatoses it is preferable to perform genetic linkage studies utilizing candidate genes directly as polymorphic markers. The PCR-based keratin 1 alleles characterized here, together with previously described PCR-based size variants in the keratin 10 gene, provide useful markers for the keratin clusters on chromosome 12 and 17, respectively. C1 NIAMSD, SKIN BIOL BRANCH, BLDG 6, ROOM 427, BETHESDA, MD 20892 USA. FREE UNIV BERLIN, MED CTR RUDOLF VIRCHOW, INST EXPTL ONCOL & TRANSPLANTAT MED, W-1000 BERLIN 33, GERMANY. NR 47 TC 42 Z9 43 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1992 VL 99 IS 6 BP 697 EP 702 DI 10.1111/1523-1747.ep12614149 PG 6 WC Dermatology SC Dermatology GA KF927 UT WOS:A1992KF92700005 PM 1281859 ER PT J AU GU, ZQ DECOSTA, BR WONG, G RICE, KC SKOLNICK, P AF GU, ZQ DECOSTA, BR WONG, G RICE, KC SKOLNICK, P TI SYNTHESIS OF [H-3] TERT-BUTYL 8-CHLORO-5,6-DIHYDRO-5-METHYL-6-OXO-4H-IMIDAZO[1,5-A][1,4]BENZODIAZEPINE 3-CARBOXYLATE, A SELECTIVE, HIGH-AFFINITY LIGAND FOR THE DIAZEPAM INSENSITIVE (DI) SUBTYPE OF THE BENZODIAZEPINE RECEPTOR SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE IMIDAZOBENZODIAZEPINE; DIAZEPAM INSENSITIVE; BENZODIAZEPINE RECEPTOR; RO-15-4513; TRITIUM LABELING; GABA(A)-RECEPTOR ID ALCOHOL ANTAGONIST; RO 15-4513; BINDING; RAT; IMIDAZOBENZODIAZEPINE; ETHANOL AB The preparation of [H-3]-labelled tert-butyl 8-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine 3-carboxylate (TClB, 6), a high affinity ligand for the diazepam insensitive (DI) subtype of the benzodiazepine receptor (BZR) is described. Synthesis of [H-3]TClB was accomplished in 4 steps starting from 5-chloroisatoic anhydride. Tritium-label introduction was achieved in the final step by selective catalytic tritiolysis in 62% radiochemical yield with quantitative isotopic incorporation. C1 NIDDKD, NEUROSCI LAB, BETHESDA, MD 20892 USA. RP GU, ZQ (reprint author), NIDDKD, MED CHEM LAB, BETHESDA, MD 20892 USA. NR 25 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD DEC PY 1992 VL 31 IS 12 BP 1049 EP 1055 DI 10.1002/jlcr.2580311213 PG 7 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA KA889 UT WOS:A1992KA88900012 ER PT J AU KAY, LE BULL, TE NICHOLSON, LK GRIESINGER, C SCHWALBE, H BAX, A TORCHIA, DA AF KAY, LE BULL, TE NICHOLSON, LK GRIESINGER, C SCHWALBE, H BAX, A TORCHIA, DA TI THE MEASUREMENT OF HETERONUCLEAR TRANSVERSE RELAXATION-TIMES IN AX3 SPIN SYSTEMS VIA POLARIZATION-TRANSFER TECHNIQUES SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; NMR-SPECTROSCOPY; PROTEINS; ENHANCEMENT; MACROMOLECULES; SIGNALS; N-15; CONSTANTS; DYNAMICS; SPECTRA C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,BIOPHYS LAB,BETHESDA,MD 20892. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. UNIV FRANKFURT,INST ORGAN CHEM,W-6000 FRANKFURT 50,GERMANY. RI Schwalbe, Harald/F-9023-2010 OI Schwalbe, Harald/0000-0001-5693-7909 NR 39 TC 69 Z9 70 U1 1 U2 10 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON PD DEC PY 1992 VL 100 IS 3 BP 538 EP 558 DI 10.1016/0022-2364(92)90058-F PG 21 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA KF538 UT WOS:A1992KF53800006 ER PT J AU MAHER, ER BENTLEY, E PAYNE, SJ LATIF, F RICHARDS, FM CHIANO, M HOSOE, S YATES, JRW LINEHAN, M BARTON, DE GLENN, G AFFARA, NA LERMAN, M ZBAR, B FERGUSONSMITH, MA AF MAHER, ER BENTLEY, E PAYNE, SJ LATIF, F RICHARDS, FM CHIANO, M HOSOE, S YATES, JRW LINEHAN, M BARTON, DE GLENN, G AFFARA, NA LERMAN, M ZBAR, B FERGUSONSMITH, MA TI PRESYMPTOMATIC DIAGNOSIS OF VONHIPPEL-LINDAU DISEASE WITH FLANKING DNA MARKERS SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID SMALL REGION; CHROMOSOME-3 AB Von Hippel-Lindau (VHL) disease is a dominantly inherited cancer syndrome characterised by the development of retinal, cerebellar, and spinal haemangioblastomas, renal cell carcinoma, and phaeochromocytoma. The gene for VHL disease has been mapped to chromosome 3p2S-p26 and flanking markers identified. We have investigated the usefulness of currently available DNA markers for the presymptomatic diagnosis of VHL disease. In the first part of this investigation, genetic linkage data from two previously published studies were updated and reanalysed to provide accurate estimates of sex specific recombination fractions and to confirm that there is no evidence of locus heterogeneity. In the second part of this study, 14 families containing 23 asymptomatic subjects at 50% prior risk of VHL disease were investigated with closely linked DNA markers (RAF1, D3S18, D3S732). Seventeen subjects were informative with one or more markers, six of whom were informative at markers flanking the VHL disease gene. By combining age related and DNA based risk information the carrier risk for 11 subjects was reduced to < 2%. C1 E ANGLIAN REG GENET SERV,MOLEC DIAGNOST LAB,CAMBRIDGE,ENGLAND. NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD 21701. NCI,SURG BRANCH,BETHESDA,MD 20892. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE,ENGLAND. RP MAHER, ER (reprint author), ADDENBROOKES HOSP,DEPT CLIN GENET,HILLS RD,CAMBRIDGE CB2 2QQ,ENGLAND. RI Barton, David/B-9460-2008; MAHER, EAMONN/A-9507-2008; OI MAHER, EAMONN/0000-0002-6226-6918; Barton, David E/0000-0002-2031-9719 NR 14 TC 17 Z9 17 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD DEC PY 1992 VL 29 IS 12 BP 902 EP 905 DI 10.1136/jmg.29.12.902 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA KD375 UT WOS:A1992KD37500013 PM 1362224 ER PT J AU FARSHID, M TABOR, E AF FARSHID, M TABOR, E TI EXPRESSION OF ONCOGENES AND TUMOR SUPPRESSOR GENES IN HUMAN HEPATOCELLULAR-CARCINOMA AND HEPATOBLASTOMA CELL-LINES SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HEPATITIS-B VIRUS; HEPATOBLASTOMA; HEPATOCELLULAR CARCINOMA; ONCOGENE; TUMOR SUPPRESSOR GENE ID HUMAN HEPATOMA; P53 GENE; CANCER; RAS; TRANSFORMATION; MUTATION; DNA AB The expression of nine oncogenes (c-myc, N-myc, N-ras, H-ras, k-ras, abl, fos, src, and raf) and two tumor suppressor genes (p53 and RB) were studied by northern blot hybridization in six human hepatocellular carcinoma or hepatoblastoma cell lines (PLC/PRF/5, Hep3B, Hep G2, 2.2.15, HLE, and HLF) and in a human embryonic lung fibroblast cell line (WI-38) to look for differences that might be associated with the presence (PLC/PRF/5, Hep3B, and 2.2.15) or absence (Hep G2, HLE, and HLF) of integrated hepatitis B virus (HBV) DNA. The levels of expression of the oncogenes and tumor suppressor genes were unrelated to the presence or absence of integrated HBV-DNA. Furthermore, the intensity of expression of these oncogenes was no greater in the 2.2.15 cell line (consisting of Hep G2 cells transfected with hepatitis B virus) than in untransfected Hep G2 cells. C1 NCI,BETHESDA,MD 20892. NR 24 TC 32 Z9 32 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 DEC PY 1992 VL 38 IS 4 BP 235 EP 239 DI 10.1002/jmv.1890380402 PG 5 WC Virology SC Virology GA KA807 UT WOS:A1992KA80700001 PM 1335479 ER PT J AU WILLIAMSON, LC FITZGERALD, SC NEALE, EA AF WILLIAMSON, LC FITZGERALD, SC NEALE, EA TI DIFFERENTIAL-EFFECTS OF TETANUS TOXIN ON INHIBITORY AND EXCITATORY NEUROTRANSMITTER RELEASE FROM MAMMALIAN SPINAL-CORD CELLS IN CULTURE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE GLUTAMATE; GLYCINE; NEURONAL CELL CULTURES; SYNAPTIC BLOCKADE; TRANSMITTER RELEASE ID PERMEABILIZED CHROMAFFIN CELLS; AMINO-ACID RELEASE; NERVE-ENDINGS; CATECHOLAMINE RELEASE; LIGHT CHAIN; BOTULINUM-A; NEUROTOXINS; EXOCYTOSIS; GLUTAMATE; NEURONS AB The effect of tetanus toxin on depolarization-evoked and spontaneous synaptic release of inhibitory and excitatory neurotransmitters was examined in murine spinal cord cell cultures. Toxin action on the release of radiolabeled glycine and glutamate was followed over time intervals corresponding to the early phase of convulsant activity through the later phase of electrical quiescence. Tetanus toxin inhibited potassium-evoked release of [H-3]glycine and [H-3]glutamate in a time- and dose-dependent manner. Ninety minutes after the application of toxin (6 x 10(-10) M), the stimulated release of [H-3]glycine was blocked completely, whereas stimulated release of [H-3]glutamate was not blocked completely until 150-210 min after toxin application. Fragment C, the binding portion of the tetanus toxin molecule, had no effect on stimulated release of either transmitter. The spontaneous synaptic release of [H-3]glycine was blocked totally within 90 min of toxin exposure. In contrast, the spontaneous release of [H-3]glutamate, in toxin-exposed cultures, was elevated to nearly twice that of control cultures at this time. Thus, toxin-induced convulsant activity is characterized by a reduction in the spontaneous synaptic release of inhibitory neurotransmitter with a concomitant increase in the release of excitatory neurotransmitter, as well as the more rapid onset of blockade of depolarization-evoked release of inhibitory versus excitatory neurotransmitter. RP WILLIAMSON, LC (reprint author), NICHHD,DEV NEUROBIOL LAB,BLDG 36,ROOM 2A21,BETHESDA,MD 20892, USA. NR 54 TC 41 Z9 42 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 DEC PY 1992 VL 59 IS 6 BP 2148 EP 2157 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JY566 UT WOS:A1992JY56600022 PM 1359016 ER PT J AU HOSSAIN, MA MASSERANO, JM WEINER, N AF HOSSAIN, MA MASSERANO, JM WEINER, N TI EFFECTS OF ELECTROCONVULSIVE SHOCK ON TETRAHYDROBIOPTERIN AND GTP-CYCLOHYDROLASE ACTIVITY IN THE BRAIN AND ADRENAL-GLAND OF THE RAT SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ELECTROCONVULSIVE SHOCK; TETRAHYDROBIOPTERIN; GTP-CYCLOHYDROLASE; TYROSINE HYDROXYLASE; CNS; ADRENAL GLAND ID GUANOSINE TRIPHOSPHATE CYCLOHYDROLASE; CATECHOLAMINE NEURON SYSTEMS; BINDING-SITES; TYROSINE HYDROXYLATION; BIOSYNTHESIS; DEPRESSION; DOPAMINE; BIOPTERIN; COFACTOR; STRIATUM AB The effects of a single and repeated electroconvulsive shock (ECS) (300 mA, 0.2 s) on tetrahydrobiopterin (BH4) levels and GTP-cyclohydrolase activity in the brain and adrenal glands of rats were examined. Twenty-four hours after the last ECS treatment (one/day for 7 days), biopterin levels were significantly elevated in the locus coeruleus, hippocampus, frontal cortex, hypothalamus, ventral tegmental area, and adrenal gland. There were no changes in biopterin levels after a single application of ECS. GTP-cyclohydrolase activity was significantly increased in the locus coeruleus, frontal cortex, hippocampus, hypothalamus, and adrenal gland 24 h after repeated ECS and remained elevated in certain tissues up to 8 days after the last treatment. Kinetic analysis of adrenal and locus coeruleus GTP-cyclohydrolase 1 day after 7 days of ECS showed significant changes in both K(m) and V(max) values. These data suggest that the long-term increases in BH4 levels and GTP-cyclohydrolase activity after repeated ECS may play a part in the mediation of the antidepressant effects of ECS. C1 NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. RP HOSSAIN, MA (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,C-236,4200 E 9TH AVE,DENVER,CO 80262, USA. FU NINDS NIH HHS [NS 09199] NR 39 TC 10 Z9 10 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 DEC PY 1992 VL 59 IS 6 BP 2237 EP 2243 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JY566 UT WOS:A1992JY56600032 PM 1431904 ER PT J AU MAMALAKI, E KVETNANSKY, R BRADY, LS GOLD, PW HERKENHAM, M AF MAMALAKI, E KVETNANSKY, R BRADY, LS GOLD, PW HERKENHAM, M TI REPEATED IMMOBILIZATION STRESS ALTERS TYROSINE-HYDROXYLASE, CORTICOTROPIN-RELEASING HORMONE AND CORTICOSTEROID RECEPTOR MESSENGER-RIBONUCLEIC-ACID LEVELS IN RAT-BRAIN SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE; MINERALOCORTICOID RECEPTOR; PROOPIOMELANOCORTIN; STRESS; TYROSINE HYDROXYLASE ID CENTRAL AMYGDALOID NUCLEUS; PARAVENTRICULAR NUCLEUS; INSITU HYBRIDIZATION; GENE-EXPRESSION; POSTTRANSLATIONAL MECHANISMS; MINERALOCORTICOID RECEPTOR; DIFFERENTIAL REGULATION; ANTERIOR-PITUITARY; LOCUS-CERULEUS; PLASMA-LEVELS AB In situ hybridization histochemistry was used to localize and quantify the effects of acute and repeated immobilization stress on mRNA levels of tyrosine hydroxylase (TH) in catecholaminergic neurons in the locus ceruleus and substantia nigra and on mRNA levels of relevant markers of the hypothalamic-pituitary-adrenal axis, namely corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN), proopiomelanocortin in the pituitary, and mineralocorticoid receptors (MR, type I) and glucocorticoid receptors (GR, type II) in the hippocampus, PVN and pituitary. Control, acutely stressed (1 x IMO, sacrificed immediately after 2 h of immobilization), and repeatedly stressed (6 x IMO plus delay, sacrificed 24 h after 6 daily 2-h immobilizations and 6 x IMO plus challenge, sacrificed immediately after the seventh daily 2-h immobilization) male Sprague-Dawley rats were examined. TH mRNA expression was increased in the locus ceruleus in the acutely stressed and repeatedly stressed animals. The increase in TH mRNA levels was greatest in the repeatedly stressed (6 x IMO plus challenge) group. TH mRNA levels were not altered in the substantia nigra. CRH mRNA levels in the PVN were significantly increased in the three stressed groups and the increase was greatest in the 6 x IMO plus challenge group. CRH mRNA levels were increased in the central nucleus of the amygdala only after acute stress. Proopiomelanocortin mRNA levels were elevated in the anterior pituitary during acute and repeated stress, but the magnitude of the effect was largest after acute stress. The changes in the hypothalamic-pituitary-adrenal axis were accompanied by an acute stress-induced increase in MR mRNA levels in the hippocampus, MR and GR mRNA levels in the PVN and GR mRNA levels in the pituitary. MR mRNA levels continued to be elevated in the PVN in the 6 x IMO plus challenge animals. Plasma corticosterone levels were elevated in the acute and repeated stress conditions. The results show that repeated immobilization stress produces a rapid and persistent increase in mRNA expression of TH in the locus ceruleus, CRH in the PVN, and proopiomelanocortin in the anterior pituitary. The TH-containing neurons in the locus ceruleus and the CRH-containing neurons in the PVN appear to preserve the capability to respond to repeated stimulation (6 x IMO plus challenge) indicating altered feedback mechanisms under repeated stress conditions. GR and MR mRNA levels are differentially regulated in the hippocampus, PVN and pituitary by acute and repeated stress. It is of interest that the central nervous system systems which are activated during repeated stress, namely the locus ceruleus-norepinephrine system and hypothalamic-pituitary-adrenal axis, are dysregulated in melancholic depression. Further studies of the central nervous system effects of prolonged exposure to stress may help elucidate the mechanisms underlying dysregulation of the locus ceruleus-norepinephrine system and hypothalamic-pituitary-adrenal axis in depression and other stress-related psychiatric diseases. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,FUNCT NEUROANAT SECT,BLDG 36,ROOM 2D15,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. OI Herkenham, Miles/0000-0003-2228-4238 NR 70 TC 102 Z9 104 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD DEC PY 1992 VL 4 IS 6 BP 689 EP 699 DI 10.1111/j.1365-2826.1992.tb00220.x PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA KH897 UT WOS:A1992KH89700006 PM 21554656 ER PT J AU KIMMIG, HG MILES, FA SCHWARZ, U AF KIMMIG, HG MILES, FA SCHWARZ, U TI EFFECTS OF STATIONARY TEXTURED BACKGROUNDS ON THE INITIATION OF PURSUIT EYE-MOVEMENTS IN MONKEYS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TEMPORAL VISUAL AREA; RETINAL MOTION STIMULI; SMOOTH-PURSUIT; MACAQUE MONKEY; OCULAR RESPONSES; VIEWING DISTANCE; OPTOKINETIC NYSTAGMUS; UNDERLYING MECHANISMS; EXPANSION CONTRACTION; FUNCTIONAL-PROPERTIES AB 1. The initial ocular pursuit of small target spots (0.25-degrees diam) that suddenly start to move at constant speed (ramps) was recorded in four rhesus monkeys with the electromagnetic search coil technique. All target motions were horizontal, and both eyes were monitored. 2. In agreement with the observations of Keller and Khan, stationary textured backgrounds substantially reduced the initial eye acceleration achieved during pursuit but did not affect its latency. Correlation techniques were used to assess the changes in the eye speed profiles and indicated that the reduction in eye acceleration due to the background was a linear function of the logarithm of target speed over the range investigated (5-40-degrees/s), averaging 60% with the fastest targets. 3. Selectively excluding the background texture from the path of the target with a horizontal strip of card (vertical width, 4-degrees) reduced the impact of the background only slightly, and, even when the vertical width of the card was increased to 60-degrees, the effect of the background was not entirely eliminated. Thus the effect involves regions of the visual field well beyond the target and is not due simply to the reduced physical salience (contrast) of the target spot. Such spatially remote interactions suggest that the neurons decoding the target's motion have ver-v extensive visual receptive fields. 4. Textured backgrounds also caused similar reductions in the eye acceleration during initial pursuit when, before the ramps, the fixated target spots stepped forward, i.e., stepped in the direction of the subsequent ramps (step ramps). In this situation, as with no steps, initial target ramps were foveofugal. When the fixated target spots were stepped back before moving forward so that initial target ramps were foveopetal, textured backgrounds now also delayed the onset of pursuit, and the reductions in eye acceleration were not seen until some time later when tracking resulted from foveofugal target-ramp motion. Selectively excluding the texture from the path of the target with a narrow strip of card eliminated any delays in the onset of pursuit to step ramps, but the later reductions in eye acceleration were still evident. These step-ramp data indicate that the mechanisms decoding foveofugal and foveopetal target ramps differ markedly in their sensitivity to textured backgrounds. That backgrounds can influence the latency and the initial eye acceleration independently is consistent with the idea that there are independent trigger and drive mechanisms for the decoding of target motions. 5. A textured background seen only by one eye reduced the eye acceleration achieved during the initial pursuit of moving targets seen only by the other eye: interocular transfer. The reduction in eye acceleration in this situation averaged 61% of the reduction observed during normal binocular viewing, indicating that a substantial part of the effect of the background must occur at a site that receives inputs from both of the eyes and hence is mediated by the CNS. 6. Untextured backgrounds (Ganzfeld) seen only by one eve generally had minor effects on the initial pursuit of moving targets seen only by the other eye except when the luminance of those backgrounds was temporally modulated: brief (10-mus) flashes of the Ganzfeld during the initial target motion caused an abrupt hesitation in the eye speed profile with a mean latency of 41 +/- 3 (SD) ms. Thus temporally or spatially modulated backgrounds can adversely affect the initiation of pursuit, presumably reflecting the temporospatial characteristics of the neurons decoding target motion. 7. When the background consisted of random dots, shifting the target out of the plane of the background (with the use of a special dichoptic viewing arrangement) reduced the impact of that background on the initiation of pursuit. In this situation the monkey probably sees the background images as both disparate (diplopic) and blurred and either (or both) factors could be critical in determining the effect of the background. However, if the background consisted of regular vertical stripes, then, in two of three monkeys, when the binocular parallax of the background reached the wavelength of the stripes (eliminating their binocular disparity), the background once more exerted its full effect. Thus, in these two monkeys, binocularly disparate background images had less impact on pursuit initiation than nondisparate ones. This is consistent with the idea that the decoding mechanism is sensitive to binocular disparity and optimally responsive to object motion in the plane of regard. features necessitating cortical processing. 8. In the experiments with the special dichoptic viewing arrangement, the control trials involved pursuit against a dark background with varying amounts of ocular convergence. Under these conditions, initial pursuit responses were a linear function of the inverse of the distance to the required plane of convergence. This may be linked to the known dependence of early ocular following on the inverse of the viewing distance and may reflect mediation by the same neuronal pathway(s). 9. We conclude that the masking effects of backgrounds can be used to probe the visual properties of the neuronal mechanisms underlying the initiation of pursuit eye movements. RP MILES, FA (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,RM 10C101,BETHESDA,MD 20892, USA. NR 61 TC 57 Z9 57 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1992 VL 68 IS 6 BP 2147 EP 2164 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA KE868 UT WOS:A1992KE86800020 PM 1491264 ER PT J AU CASANOVA, MF COMPARINI, SO KIM, RW KLEINMAN, JE AF CASANOVA, MF COMPARINI, SO KIM, RW KLEINMAN, JE TI STAINING INTENSITY OF BRAIN IRON IN PATIENTS WITH SCHIZOPHRENIA - A POSTMORTEM STUDY SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID TARDIVE-DYSKINESIA; ABNORMALITIES; SYSTEM AB Evidence derived from both pharmacological and postmortem studies suggests that a disturbance of brain iron metabolism is involved in the pathophysiology of schizophrenia; i.e., the distribution of iron parallels that of dopamine, and variations in its brain concentration selectively modulate the binding affinity of the dopaminergic (D2) receptor. In the present study the authors examined the staining intensity of brain iron in postmortem specimens of 9 schizophrenic (SC) patients and 17 age-matched controls. Coronal sections were stained with the Perls's technique, photographed, and then studied using a computerized image analysis system. Optical density measurements were taken from the caudate nucleus, putamen, globus pallidus, and substantia nigra. This study revealed significant differences between groups only for the staining intensity of iron in the caudate nucleus (P < 0.005). A review of the literature suggests that this finding may be the result of neuroleptic therapy and not a primary pathological feature of schizophrenia. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. DC MED EXAMINERS OFF,WASHINGTON,DC. NR 30 TC 15 Z9 15 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1992 VL 4 IS 1 BP 36 EP 41 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HC253 UT WOS:A1992HC25300006 PM 1627959 ER PT J AU PAZZAGLIA, PJ POST, RM AF PAZZAGLIA, PJ POST, RM TI CONTINGENT TOLERANCE AND RERESPONSE TO CARBAMAZEPINE - A CASE-STUDY IN A PATIENT WITH TRIGEMINAL NEURALGIA AND BIPOLAR DISORDER SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID TERM FOLLOW-UP; SODIUM VALPROATE; BACLOFEN; THERAPY; EPILEPSY; EFFICACY AB This retrospective single-case study demonstrates the development of tolerance and reresponse to carbamazepine in a patient with coexisting trigeminal neuralgia and manic-depressive illness. After an initial positive response, tolerance to the antinociceptive and psychotropic effects of carbamazepine appeared during treatment, despite increasing doses. As in preclinical studies of contingent tolerance, periods of carbamazepine discontinuation were associated with reresponse following reinstitution. These are the first clinical data interpreted in a contingent tolerance formulation with reresponse following a medication-free interval. Controlled and prospective studies are needed of the reliability and the pathophysiological and therapeutic implications of this phenomenon. C1 NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 38 TC 27 Z9 27 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1992 VL 4 IS 1 BP 76 EP 81 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HC253 UT WOS:A1992HC25300014 PM 1627967 ER PT J AU PARKS, RW CROCKETT, DJ MANJI, HK AMMANN, W AF PARKS, RW CROCKETT, DJ MANJI, HK AMMANN, W TI ASSESSMENT OF BROMOCRIPTINE INTERVENTION FOR THE TREATMENT OF FRONTAL-LOBE SYNDROME - A CASE-STUDY SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Letter C1 UNIV BRITISH COLUMBIA,DEPT RADIOL,VANCOUVER V6T 1W5,BC,CANADA. NIMH,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,DEPT PSYCHIAT,VANCOUVER V6T 1W5,BC,CANADA. RP PARKS, RW (reprint author), SO ILLINOIS UNIV,SCH MED,DEPT PSYCHIAT,POB 19230,SPRINGFIELD,IL 62794, USA. FU NIA NIH HHS [P30 AG08014]; NIMH NIH HHS [R01 MH/AG41821-01, R01 MH/AG41821-02] NR 7 TC 12 Z9 12 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1992 VL 4 IS 1 BP 109 EP 111 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HC253 UT WOS:A1992HC25300018 PM 1627954 ER PT J AU LEE, WH JAVEDAN, S BONDY, CA AF LEE, WH JAVEDAN, S BONDY, CA TI COORDINATE EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR SYSTEM COMPONENTS BY NEURONS AND NEUROGLIA DURING RETINAL AND CEREBELLAR DEVELOPMENT SO JOURNAL OF NEUROSCIENCE LA English DT Article ID FACTOR-BINDING-PROTEINS; CENTRAL-NERVOUS-SYSTEM; I IGF-I; GENE-EXPRESSION; MESSENGER-RNA; RECEPTOR GENE; RAT EMBRYO; LOCALIZATION; BRAIN; CULTURE AB The interactions of insulin-like growth factors (IGFs) with the type I IGF receptor are modulated by a family of high-affinity IGF binding proteins (IGFBPs). One of these, IGFBP2, demonstrates a striking spatiotemporal relationship with IGF-I during cerebellar and retinal development. IGF-I mRNA is transiently expressed in large projection neurons-cerebellar Purkinje and retinal ganglion cells-while IGFBP2 mRNA is selectively expressed by contiguous neuroglia-Bergmann glia in the cerebellum and Muller cells and astrocytes of the nerve fiber layer in the retina. IGF-I and IGFBP2 gene expression is not only neuroanatomically coordinated but also temporally synchronized, peaking together during the postnatal maturation of these structures. This pattern of IGF system expression suggests that IGFBP2 is closely related to IGF-I's action in the developing nervous system. RP LEE, WH (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 136 Z9 138 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC PY 1992 VL 12 IS 12 BP 4737 EP 4744 PG 8 WC Neurosciences SC Neurosciences & Neurology GA KC840 UT WOS:A1992KC84000015 PM 1281494 ER PT J AU FITZGERALD, SC WILLIS, MA YU, C RIGATTO, H AF FITZGERALD, SC WILLIS, MA YU, C RIGATTO, H TI IN SEARCH OF THE CENTRAL RESPIRATORY NEURONS .1. DISSOCIATED CELL-CULTURES OF RESPIRATORY AREAS FROM THE UPPER MEDULLA SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE NEURONAL CELL CULTURES; NUCLEUS AMBIGUUS; NUCLEUS-TRACTUS-SOLITARIUS; ASTROCYTE CULTURES; GLIAL CULTURES ID MOUSE SPINAL-CORD; RATS AB Dissociated cells from the areas of the nucleus ambiguus and the nucleus tractus solitarius obtained by tissue punch or block dissection from coronal slices of the medulla at the level of the obex were cultured from fetal rats at 18 to 21 days gestation. The dissociated neurons were plated either directly in vitrogen-coated 35 mm tissue culture dishes or in such dishes which had been seeded with subcultures of cortex- or medulla-derived astrocytes. After the astrocytes reached confluency and were treated with an antimitotic agent, dissociated nucleus ambiguus or nucleus tractus solitarius was plated at 0.5-1.0 x 10(6) cells per dish. Neurons grew well on monolayers of medullary or cortical astrocytes, but survived poorly on vitrogen-coated dishes without a cellular substrate. Rat medulla was preferred as the source of astrocytes. Tissue dissociation with papain rather than trypsin produced less cellular debris, and the neuronal yield from the tissue was higher. The neuronal population was heterogenous in morphology including small and large bipolar, pyramidal, and multipolar cells. Neurons sensitive to CO2 and/or low pH (Rigatto et al., J Neurosci Res 33:590-597, 1992) did not appear to have any definitive morphologic characteristics, but most were multipolar. These neurons stained well with antibodies to neuron-specific enolase and Fragment C of tetanus toxin, but not to choline acetyltransferase (ChAT). These findings suggest that neurons possibly responsible for the central regulation of respiration can be maintained for several weeks in dissociated cell culture, providing a system for neurotransmitter, electrophysiological, and morphological studies. C1 UNIV MANITOBA,DEPT PEDIAT PHYSIOL & REPROD MED,WINNIPEG R3T 2N2,MANITOBA,CANADA. RP FITZGERALD, SC (reprint author), NICHHD,DEV NEUROBIOL LAB,BLDG 36,ROOM 2A21,BETHESDA,MD 20892, USA. NR 18 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC PY 1992 VL 33 IS 4 BP 579 EP 589 DI 10.1002/jnr.490330410 PG 11 WC Neurosciences SC Neurosciences & Neurology GA JZ849 UT WOS:A1992JZ84900009 PM 1484391 ER PT J AU RIGATTO, H FITZGERALD, SC WILLIS, MA YU, C AF RIGATTO, H FITZGERALD, SC WILLIS, MA YU, C TI IN SEARCH OF THE CENTRAL RESPIRATORY NEURONS .2. ELECTROPHYSIOLOGIC STUDIES OF MEDULLARY FETAL CELLS INHERENTLY SENSITIVE TO CO2 AND LOW PH SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE RESPIRATORY CENTER; RESPIRATORY CONTROL; MEDULLARY NEURONS; DISSOCIATED CELL CULTURE ID MOUSE SPINAL-CORD; VENTRAL MEDULLA; CARBON-DIOXIDE; RAT; ORGANIZATION; CULTURES; INVITRO; MAMMALS; CALCIUM; RHYTHM AB Although extensively pursued, the central respiratory neurons have remained elusive. We departed from the more conventional physiologic and morphologic methods of system and tissue examination and cultured dissociated fetal rat cells (Fitzgerald et al., J Neurosci Res 33:579-589, 1992) from the area of the nucleus ambiguus and the nucleus tractus solitarius located within the 2 mm rostral to the obex. Pacemaker-like cells, with a regular single or bursting activity, studied at 3-5 weeks of age, responded to very small pulses of CO2 (50 ms) and low pH with an increase in spike frequency and a decrease in spike amplitude. Other irregularly beating or silent cells did not respond or else required very large pulses (>200 ms) to do so. The pacemaker cells also responded to hypoxia induced by administration of sodium hydrosulfite with an increase in spike frequency and amplitude; high oxygen (>600 torr) and adenosine produced a decrease in electrical activity. Most of these cells were multipolar after staining with antibodies to neuron-specific enolase (NSE) and Fragment C of tetanus toxin. They did not stain for choline acetyltransferase (ChAT). The results suggest that these cultured cells, expressing a phenotype inherently responsive to CO2 and low pH, have the characteristics of central respiratory chemoreceptors, and may be involved in the generation of the respiratory rhythm. C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. UNIV MANITOBA,DEPT PHYSIOL & REPROD MED,WINNIPEG R3T 2N2,MANITOBA,CANADA. RP RIGATTO, H (reprint author), UNIV MANITOBA,DEPT PEDIAT,RM WR125-735 NOTRE DAME AVE,WINNIPEG R3L 0L8,MANITOBA,CANADA. NR 34 TC 31 Z9 31 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC PY 1992 VL 33 IS 4 BP 590 EP 597 DI 10.1002/jnr.490330411 PG 8 WC Neurosciences SC Neurosciences & Neurology GA JZ849 UT WOS:A1992JZ84900010 PM 1484392 ER PT J AU KUMAR, A BRAUN, A SCHAPIRO, M GRADY, C CARSON, R HERSCOVITCH, P AF KUMAR, A BRAUN, A SCHAPIRO, M GRADY, C CARSON, R HERSCOVITCH, P TI CEREBRAL GLUCOSE METABOLIC RATES AFTER 30 AND 45 MINUTE ACQUISITIONS - A COMPARATIVE-STUDY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; ALZHEIMERS-DISEASE; 1 year occurred in 12.3% of patients following injection. C1 NIDOCD,VOICE & SPEECH SECT,BETHESDA,MD. OI Ludlow, Christy/0000-0002-2015-6171 NR 0 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0892-1997 J9 J VOICE JI J. Voice PD DEC PY 1992 VL 6 IS 4 BP 380 EP 386 DI 10.1016/S0892-1997(05)80038-4 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA JY941 UT WOS:A1992JY94100015 ER PT J AU PASSANITI, A AF PASSANITI, A TI EXTRACELLULAR MATRIX-CELL INTERACTIONS - MATRIGEL AND COMPLEX CELLULAR-PATTERN FORMATION SO LABORATORY INVESTIGATION LA English DT Letter RP PASSANITI, A (reprint author), NIA,BETHESDA,MD 20892, USA. NR 3 TC 14 Z9 14 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1992 VL 67 IS 6 BP 804 EP 804 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA KD399 UT WOS:A1992KD39900015 PM 1460871 ER PT J AU GRANT, D CID, M KIBBEY, MC KLEINMAN, H AF GRANT, D CID, M KIBBEY, MC KLEINMAN, H TI EXTRACELLULAR MATRIX-CELL INTERACTIONS - MATRIGEL AND COMPLEX CELLULAR-PATTERN FORMATION SO LABORATORY INVESTIGATION LA English DT Letter ID RECONSTITUTED BASEMENT-MEMBRANE; CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; EPITHELIAL-CELLS; DIFFERENTIATION; LAMININ; INVITRO RP GRANT, D (reprint author), NIH,BETHESDA,MD 20892, USA. NR 18 TC 6 Z9 6 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1992 VL 67 IS 6 BP 805 EP 806 PG 2 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA KD399 UT WOS:A1992KD39900017 PM 1460872 ER PT J AU LEBOVICS, RS HOFFMAN, GS LEAVITT, RY KERR, GS TRAVIS, WD KAMMERER, W HALLAHAN, C ROTTEM, M FAUCI, AS AF LEBOVICS, RS HOFFMAN, GS LEAVITT, RY KERR, GS TRAVIS, WD KAMMERER, W HALLAHAN, C ROTTEM, M FAUCI, AS TI THE MANAGEMENT OF SUBGLOTTIC STENOSIS IN PATIENTS WITH WEGENERS GRANULOMATOSIS SO LARYNGOSCOPE LA English DT Article ID TRACHEA AB Wegener's granulomatosis (WG) is a multisystem inflammatory disease characterized by vasculitis, granuloma formation, and necrosis. Among 158 patients treated at the National Institutes of Health during the past 24 years, 145 (92%) had an otolaryngologic manifestation of their disease and 25 (16%) had subglottic stenosis (SGS). SGS varied from asymptomatic to life-threatening. Sixteen (80%) of 20 patients with fixed SGS required surgical intervention, including manual dilations, carbon-dioxide laser resections, and laryngotracheoplasty (LTP). LTP was performed with and without microvascular reconstruction. Thirteen of the patients required tracheostomy and all 13 were ultimately decannulated. Five patients who repeatedly failed dilations and/or endoscopic laser surgery underwent LTP. Since 1987, two patients have undergone LTP with microvascular free flaps. Both patients were subsequently decannulated. The authors' experience demonstrates that management of SGS in WG is complex, requiring individualized frequent multimodality interventions to achieve satisfactory results. Microvascular laryngotracheal reconstruction should be considered in the surgical armamentarium for patients with persistent stenoses. C1 NIAID,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. RP LEBOVICS, RS (reprint author), NIDCD,BLDG 10,RM 5N226,BETHESDA,MD 20892, USA. NR 14 TC 93 Z9 101 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 1992 VL 102 IS 12 BP 1341 EP 1345 DI 10.1288/00005537-199212000-00005 PN 1 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA KT260 UT WOS:A1992KT26000005 PM 1453838 ER PT J AU KALBERER, JT AF KALBERER, JT TI WHEN SOCIAL-SCIENCE RESEARCH COMPETES WITH BIOMEDICAL-RESEARCH SO MEDICAL ANTHROPOLOGY QUARTERLY LA English DT Note RP KALBERER, JT (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ANTHROPOLOGICAL ASSOC PI ARLINGTON PA 4350 NORTH FAIRFAX DRIVE SUITE 640, ARLINGTON, VA 22203 SN 0745-5194 J9 MED ANTHROPOL Q JI Med. Anthropol. Q. PD DEC PY 1992 VL 6 IS 4 BP 391 EP 394 PG 4 WC Anthropology; Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Anthropology; Public, Environmental & Occupational Health; Biomedical Social Sciences GA KB915 UT WOS:A1992KB91500005 ER PT J AU KHAR, A DESHPANDE, G GERSTEN, DM HEARING, VJ AF KHAR, A DESHPANDE, G GERSTEN, DM HEARING, VJ TI THE RELATIONSHIP OF TUMOR-ANTIGENS TO NORMAL PROTEINS, WITH SPECIAL REFERENCE TO ALBUMIN-LIKE MELANOMA ANTIGENS SO MELANOMA RESEARCH LA English DT Article DE MELANOMA; TUMOR ANTIGEN C1 NCI,CELL BIOL LAB,BLDG 37,ROOM 1B22,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD DEC PY 1992 VL 2 IS 5-6 BP 363 EP 367 DI 10.1097/00008390-199212000-00010 PG 5 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA KL162 UT WOS:A1992KL16200010 PM 1292784 ER PT J AU GOTTESMAN, S MAURIZI, MR AF GOTTESMAN, S MAURIZI, MR TI REGULATION BY PROTEOLYSIS - ENERGY-DEPENDENT PROTEASES AND THEIR TARGETS SO MICROBIOLOGICAL REVIEWS LA English DT Review ID HEAT-SHOCK PROTEIN; N-END RULE; UBIQUITIN-CONJUGATING ENZYME; MOLECULAR-WEIGHT PROTEASES; ESCHERICHIA-COLI PROTEINS; DIVISION INHIBITOR SULA; MALTOSE-BINDING PROTEIN; REQUIRES ATP HYDROLYSIS; SHORT-LIVED PROTEINS; CYCLE MUTANT TS85 AB A number of critical regulatory proteins in both prokaryotic and eukaryotic cells are subject to rapid, energy-dependent proteolysis. Rapid degradation combined with control over biosynthesis provides a mechanism by which the availability of a protein can be limited both temporally and spatially. Highly unstable regulatory proteins are involved in numerous biological functions, particularly at the commitment steps in developmental pathways and in emergency responses. The proteases involved in energy-dependent proteolysis are large proteins with the ability to use ATP to scan for appropriate targets and degrade complete proteins in a processive manner. These cytoplasmic proteases are also able to degrade many abnormal proteins in the cell. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP GOTTESMAN, S (reprint author), NCI,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 252 TC 426 Z9 433 U1 2 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0146-0749 J9 MICROBIOL REV JI Microbiol. Rev. PD DEC PY 1992 VL 56 IS 4 BP 592 EP 621 PG 30 WC Microbiology SC Microbiology GA KB375 UT WOS:A1992KB37500006 PM 1480111 ER PT J AU GOLDSTEIN, SR HUBIN, T SMITH, TG AF GOLDSTEIN, SR HUBIN, T SMITH, TG TI AN IMPROVED NO-MOVING-PARTS VIDEO-RATE CONFOCAL MICROSCOPE SO MICRON AND MICROSCOPICA ACTA LA English DT Article; Proceedings Paper CT CONF ON BIOMEDICAL IMAGE PROCESSING AND 3-DIMENSIONAL MICROSCOPY CY FEB 10-13, 1992 CL SAN JOSE, CA SP SOC PHOTO OPT INSTRUMENTAT ENGINEERS, INT SCI & TECHNOL DE IMAGE DISSECTOR TUBE; VIDEO-RATE CONFOCAL MICROSCOPE AB Several years ago our research program developed a video-rate confocal microscope with no moving parts, based on synchronizing and aligning the scan of an image dissector tube (IDT) with the light returning from a microscope stage that has been acousto-optically scanned by a laser beam. Improvements on the original system have recently been completed. The laser power has been substantially increased and the laser scan is now brought into the Nikon Diaphot inverted microscope through the epi-illumination port. Aberrations in the scanned beam have been reduced by performing the beam shaping required by the acousto-optic deflectors using prisms instead of cylindrical lenses. The IDT is located at the side camera output port at the end of a simple, efficient light path. The new system is described in detail and results obtained using the microscope in reflection and fluorescence mode are presented. C1 NINCDS,NEUROPHYSIOL LAB,BETHESDA,MD 20892. CHESAPEAKE LASER SYST INC,LANHAM,MD 20706. RP GOLDSTEIN, SR (reprint author), NIH,NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 2 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 0739-6260 J9 MICRON MICROSC ACTA PD DEC PY 1992 VL 23 IS 4 BP 437 EP 446 DI 10.1016/0739-6260(92)90019-A PG 10 WC Microscopy SC Microscopy GA JZ925 UT WOS:A1992JZ92500005 ER PT J AU RAWLINGS, DJ FUJIOKA, H FRIED, M KEISTER, DB AIKAWA, M KASLOW, DC AF RAWLINGS, DJ FUJIOKA, H FRIED, M KEISTER, DB AIKAWA, M KASLOW, DC TI ALPHA-TUBULIN-II IS A MALE-SPECIFIC PROTEIN IN PLASMODIUM-FALCIPARUM SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE EXFLAGELLATION; PLASMODIUM-FALCIPARUM; PLASMODIUM-GALLINACEUM; SEX-SPECIFIC; SEXUAL STAGE; TUBULIN ID TRANSMISSION-BLOCKING ANTIBODIES; MALARIA PARASITES; SURFACE-ANTIGENS; GALLINACEUM; EXPRESSION; GAMETOGENESIS; MOSQUITO; GENES; FERTILIZATION; SEQUENCE AB The tubulin gene family in Plasmodium falciparum consists of one beta-tubulin and two alpha-tubulin genes (alpha-tubulin I and II). We present here data indicating that alpha-tubulin II is expressed only in male sexual stage parasites. An IgM mAb, 5E7, specifically reacted with stage III (day 4-5) through mature (day 10-11) male gametocytes and with emerging, exflagellating, or freely moving male gametes. No reactivity was detected in female gametocytes, female gametes, sporozoites, or asexual parasites. mAb 5E7 also specifically recognized male gametes of the avian parasite, Plasmodium gallinaceum, and immunoblotted a 50 kDa protein in extracts of male gametes from both species. This 50 kDa antigen was localized by immunoelectron microscopy to axonemes of male gametes in a pattern similar to that obtained with anti-alpha- and anti-beta-tubulin antibodies. Furthermore, mAb 5E7 specifically reacted with recombinant alpha-tubulin II protein obtained using the PCR-amplified alpha-tubulin II gene from a gametocyte-specific cDNA library. The sex-specific expression of alpha-tubulin II and its localization to axoneme of the male parasite suggest a role for this molecule in the morphologic changes that occur during exflagellation and in the motility of the parasite. alpha-Tubulin II and mAb 5E7 may prove useful tools in studies of the biology of sexual stage differentiation and development in P. falciparum in addition to the general understanding of post-translational modifications of tubulin isoforms. C1 NIAID,MALARIA RES INST,BLDG 4,ROOM B1-37,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,SCH MED,INST PATHOL,CLEVELAND,OH 44106. FU NIAID NIH HHS [AI-10645] NR 29 TC 69 Z9 69 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD DEC PY 1992 VL 56 IS 2 BP 239 EP 250 DI 10.1016/0166-6851(92)90173-H PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA KE274 UT WOS:A1992KE27400006 PM 1484548 ER PT J AU GAUEN, LKT KONG, ANT SAMELSON, LE SHAW, AS AF GAUEN, LKT KONG, ANT SAMELSON, LE SHAW, AS TI P59FYN TYROSINE KINASE ASSOCIATES WITH MULTIPLE T-CELL RECEPTOR SUBUNITS THROUGH ITS UNIQUE AMINO-TERMINAL DOMAIN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; VESICULAR STOMATITIS-VIRUS; POLYMERASE CHAIN-REACTION; ANTIGEN RECEPTOR; PROTEIN-KINASE; MONOCLONAL-ANTIBODIES; PHOSPHOLIPID-VESICLES; TRANSFORMING PROTEIN; SIGNAL TRANSDUCTION; CYTOPLASMIC DOMAINS AB Several lines of evidence link the protein tyrosine kinase p59fyn to the T-cell receptor. The molecular basis of this interaction has not been established. Here we show that the tyrosine kinase p59fyn can associate with chimeric proteins that contain the cytoplasmic domains of CD3 epsilon, gamma, zeta (zeta), and eta. Mutational analysis of the zeta cytoplasmic domain demonstrated that the membrane-proximal 41 residues of zeta are sufficient for p59fyn binding and that at least two p59fyn binding domains are present. The association of p59fyn with the zeta chain was specific, as two closely related Src family protein tyrosine kinases, p60src and p56lck, did not associate with a chimeric protein that contained the cytoplasmic domain of zeta. Mutational analysis of p59fyn revealed that a 10-amino-acid sequence in the unique amino-terminal domain of p59fyn was responsible for the association with zeta. These findings support evidence that p59fyn is functionally and structurally linked to the T-cell receptor. More importantly, these studies support a critical role for the unique amino-terminal domains of Src family kinases in the coupling of tyrosine kinases to the signalling pathways of cell surface receptors. C1 WASHINGTON UNIV, SCH MED, DEPT PATHOL, BOX 8118, ST LOUIS, MO 63110 USA. NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. NR 43 TC 141 Z9 141 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1992 VL 12 IS 12 BP 5438 EP 5446 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JZ258 UT WOS:A1992JZ25800017 ER PT J AU WEK, RC CANNON, JF DEVER, TE HINNEBUSCH, AG AF WEK, RC CANNON, JF DEVER, TE HINNEBUSCH, AG TI TRUNCATED PROTEIN PHOSPHATASE-GLC7 RESTORES TRANSLATIONAL ACTIVATION OF GCN4-EXPRESSION IN YEAST MUTANTS DEFECTIVE FOR THE EIF-2-ALPHA KINASE-GCN2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INITIATION FACTOR-II; DOUBLE-STRANDED-RNA; AMINO-ACID AVAILABILITY; SACCHAROMYCES-CEREVISIAE; GCN4 EXPRESSION; GLYCOGEN-SYNTHASE; GENERAL CONTROL; TYPE-1; DNA; PHOSPHORYLATION AB GCN2 is a protein kinase in Saccharomyces cerevisiae that is required for increased expression of the transcriptional activator GCN4 in amino acid-starved cells. GCN2 stimulates GCN4 synthesis at the translational level by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2). We identified a truncated form of the GLC7 gene, encoding the catalytic subunit of a type 1 protein phosphatase, by its ability to restore derepression of GCN4 expression in a strain containing the partially defective gcn2-507 allele. Genetic analysis suggests that the truncated GLC7 allele has a dominant negative phenotype, reducing the level of native type 1 protein phosphatase activity in the cell. The truncated form of GLC7 does not suppress the regulatory defect associated with a gcn2 deletion or a mutation in the phosphorylation site of eIF-2alpha (Ser-51). In addition, the presence of multiple copies of wild-type GLC7 impairs the derepression of GCN4 that occurs in response to amino acid starvation or dominant-activating mutations in GCN2. These findings suggest that the phosphatase activity of GLC7 acts in opposition to the kinase activity of GCN2 in modulating the level of eIF-2alpha phosphorylation and the translational efficiency of GCN4 mRNA. This conclusion is supported by biochemical studies showing that the truncated GLC7 allele increases the level of eIF-2alpha phosphorylation in the gcn2-507 mutant to a level approaching that seen in wild-type cells under starvation conditions. The truncated GLC7 allele also leads to reduced glycogen accumulation, indicating that this protein phosphatase is involved in regulating diverse metabolic pathways in yeast cells. C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. UNIV MISSOURI,DEPT MOLEC MICROBIOL & IMMUNOL,COLUMBIA,MO 65211. NR 59 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 DEC PY 1992 VL 12 IS 12 BP 5700 EP 5710 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JZ258 UT WOS:A1992JZ25800046 PM 1333044 ER PT J AU RAMIREZ, M WEK, RC DEALDANA, CRV JACKSON, BM FREEMAN, B HINNEBUSCH, AG AF RAMIREZ, M WEK, RC DEALDANA, CRV JACKSON, BM FREEMAN, B HINNEBUSCH, AG TI MUTATIONS ACTIVATING THE YEAST EIF-2-ALPHA KINASE GCN2 - ISOLATION OF ALLELES ALTERING THE DOMAIN RELATED TO HISTIDYL-TRANSFER-RNA SYNTHETASES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFER RNA-SYNTHETASE; DOUBLE-STRANDED-RNA; AMINO-ACID BIOSYNTHESIS; DEPENDENT PROTEIN-KINASE; INITIATION-FACTOR EIF-2; OPEN READING FRAMES; SACCHAROMYCES-CEREVISIAE; TRANSLATIONAL CONTROL; MESSENGER-RNA; REGULATORY FUNCTION AB The protein kinase GCN2 stimulates expression of the yeast transcriptional activator GCN4 at the translational level by phosphorylating the alpha subunit of translation initiation factor 2 (eIF-2alpha) in amino acid-starved cells. Phosphorylation of eIF-2alpha reduces its activity, allowing ribosomes to bypass short open reading frames present in the GCN4 mRNA leader and initiate translation at the GCN4 start codon. We describe here 17 dominant GCN2 mutations that lead to derepression of GCN4 expression in the absence of amino acid starvation. Seven of these GCN2c alleles map in the protein kinase moiety, and two in this group alter the presumed ATP-binding domain, suggesting that ATP binding is a regulated aspect of GCN2 function. Six GCN2c alleles map in a region related to histidyl-tRNA synthetases, and two in this group alter a sequence motif conserved among class II aminoacyl-tRNA synthetases that directly interacts with the acceptor stem of tRNA. These results support the idea that GCN2 kinase function is activated under starvation conditions by binding uncharged tRNA to the domain related to histidyl-tRNA synthetase. The remaining GCN2c alleles map at the extreme C terminus, a domain required for ribosome association of the protein. Representative mutations in each domain were shown to depend on the phosphorylation site in eIF-2alpha for their effects on GCN4 expression and to increase the level of eIF-2alpha phosphorylation in the absence of amino acid starvation. Synthetic GCN2c double mutations show greater derepression of GCN4 expression than the parental single mutations, and they have a slow-growth phenotype that we attribute to inhibition of general translation initiation. The phenotypes of the GCN2c alleles are dependent on GCN1 and GCN3, indicating that these two positive regulators of GCN4 expression mediate the inhibitory effects on translation initiation associated with activation of the yeast eIF-2alpha kinase GCN2. C1 NICHHD, MOLEC GENET LAB, MOLEC GENET LOWER EUKARYOTES SECT, BETHESDA, MD 20892 USA. RI Vazquez de Aldana, Carlos/B-7772-2008 OI Vazquez de Aldana, Carlos/0000-0002-4513-3654 NR 65 TC 97 Z9 98 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1992 VL 12 IS 12 BP 5801 EP 5815 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JZ258 UT WOS:A1992JZ25800056 PM 1448107 ER PT J AU PARK, D RHEE, SG AF PARK, D RHEE, SG TI PHOSPHORYLATION OF NCK IN RESPONSE TO A VARIETY OF RECEPTORS, PHORBOL-MYRISTATE ACETATE, AND CYCLIC-AMP SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHOLIPASE-C-GAMMA; PHOSPHOTYROSINE-CONTAINING PROTEINS; TYROSINE KINASE-ACTIVITY; SIGNAL TRANSDUCTION; CYTOPLASMIC PROTEIN; SH2 DOMAINS; CLONING; HOMOLOGY; ONCOGENE; BINDING AB The 47-kDa protein coimmunoprecipitated with phospholipase C (PLC)-gamma1 by anti-PLC-gamma1 monoclonal antibodies is proved to be Nck, a protein-composed almost exclusively of one SH2 and three SH3 domains. Nck and PLC-gamma1 are recognized by certain anti-PLC-gamma1 monoclonal antibodies because Nck and PLC-gamma1 share an epitope that likely is located in their SH3 domains. Nck is widely distributed in rat tissues, with an especially high level of expression in testes. The expression levels of Nck remains unchanged during the development of rat brain, whereas PLC-gamma1 decreases during the same developmental period. Stimulation of A431 cells with epidermal growth factor elicits the tight association of Nck with the epidermal growth factor receptor and phosphorylation of Nck on both serine and tyrosine residues. The phosphorylation of Nck is also enhanced in response to stimulation of the nerve growth factor receptor in PC12 cells, the T-cell receptor complex in Jurkat cells, the membrane immunoglobulin M in Daudi cells, and the low-affinity immunoglobulin G receptor (FcgammaRII) in U937 cells. The phosphorylation of Nck was also enhanced following treatment of A431 cells with phorbol 12-myristate 13-acetate or forskolin. These results suggest that Nck is a target for a variety of protein kinases that might modulate the postulated role of Nck as an adaptor for the physical and functional coordination of signalling proteins. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 44 TC 115 Z9 116 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 DEC PY 1992 VL 12 IS 12 BP 5816 EP 5823 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JZ258 UT WOS:A1992JZ25800057 PM 1333046 ER PT J AU AGUILERA, G AF AGUILERA, G TI ROLE OF ANGIOTENSIN-II RECEPTOR SUBTYPES ON THE REGULATION OF ALDOSTERONE SECRETION IN THE ADRENAL GLOMERULOSA ZONE IN THE RAT SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE ALDOSTERONE; ANGIOTENSIN-II; ANGIOTENSIN-II RECEPTOR SUBTYPE; CYCLIC AMP; INOSITOL PHOSPHATE; ADRENAL GLOMERULOSA ID SMOOTH-MUSCLE; BINDING-SITES; ANTAGONISTS; CELLS; DISCRIMINATION; GENERATION; EXPRESSION; SYSTEMS; FETUS AB The role of AII receptors subtypes, AT1 and AT2, in the regulation of aldosterone secretion was studied in adrenal glomerulosa cells and membranes from rats on normal and low sodium intake, using AII receptor subtype-specific antagonists. In adrenal glomerulosa cells, more than 90% of the receptors were AT1 and there was a good correlation between the potencies of the antagonists to inhibit ligand binding, and AII-stimulated aldosterone production and inositol phosphate formation. The inhibition of basal and ACTH-stimulated cAMP by AII was also abolished by the AT1, but not the AT2, antagonist. Sodium restriction for 6 days increased both receptor subtypes in the same proportion, but only the AT1 antagonist inhibited AII-stimulated aldosterone production. The data demonstrate that AT1 receptor mediates the regulatory actions of AII in the adrenal zona glomerulosa. RP AGUILERA, G (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT,BLDG 10,RM 10N262,BETHESDA,MD 20892, USA. NR 34 TC 58 Z9 58 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 DEC PY 1992 VL 90 IS 1 BP 53 EP 60 DI 10.1016/0303-7207(92)90101-B PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA KB456 UT WOS:A1992KB45600011 PM 1338730 ER PT J AU BANERJEE, R VONDERHAAR, BK AF BANERJEE, R VONDERHAAR, BK TI PROLACTIN-INDUCED PROTEIN-KINASE-C ACTIVITY IN A MOUSE MAMMARY CELL-LINE (NOG-8) SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE PROLACTIN; PROTEIN KINASE-C; MAMMARY CELL; NOG-8 ID NODE LYMPHOMA-CELLS; ORNITHINE DECARBOXYLASE; GLAND EXPLANTS; RAT-LIVER; RECEPTOR; CALCIUM; GROWTH; ACTIVATION; EXPRESSION; STIMULATION AB The normal mouse mammary epithelial cells, NOG-8, respond to the mitogenic signal of prolactin with a 2.5-fold increase in cell number within 3 days in vitro. When prolactin is added to subconfluent cells for 5-15 min, there is a 5-fold increase in protein kinase C activity. Upon longer exposure (24 h) to the hormone, the enzyme activity returns to that of control. The potent protein kinase C inhibitor, 1-(5-isoquinotinesulfonyl)-2-methylpiperazine dihydrochloride (H7), blocks both the prolactin-induced enzyme activity and subsequent increase in cell number. Prior to prolactin treatment, 90% of the protein kinase C activity resides in the cytosol with only 10% associated with the membranes. After only 5 min of prolactin treatment, 70% of the enzyme activity is now localized to the membranes. These data suggest that prolactin uses the protein kinase C pathway for signal transduction in NOG-8 cells thus leading to enhanced cell growth. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,RM 5B56,BETHESDA,MD 20892. NR 42 TC 31 Z9 33 U1 0 U2 0 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 DEC PY 1992 VL 90 IS 1 BP 61 EP 67 DI 10.1016/0303-7207(92)90102-C PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA KB456 UT WOS:A1992KB45600012 PM 1301398 ER PT J AU MAR, EC IADAROLA, MJ HONG, JS AF MAR, EC IADAROLA, MJ HONG, JS TI REGULATION OF THE EXPRESSION OF PROENKEPHALIN MESSENGER-RNA IN BOVINE ADRENAL CHROMAFFIN CELLS - ROLE OF PROTOONCOGENES SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID TRANSCRIPTION FACTOR AP-1; DNA-BINDING ACTIVITY; CYCLIC-AMP; TYROSINE-HYDROXYLASE; GEL-ELECTROPHORESIS; INDUCIBLE ENHANCER; GENE-EXPRESSION; C-JUN; PROTEINS; FOS C1 UNIV N CAROLINA,SCH MED,LINEBERGER COMPREHENS CANC RES CTR,CHAPEL HILL,NC 27599. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. RP MAR, EC (reprint author), NIEHS,NEUROPHARMACOL SECT,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709, USA. NR 43 TC 13 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD DEC PY 1992 VL 3 IS 6 BP 508 EP 517 DI 10.1016/1044-7431(92)90063-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA JZ617 UT WOS:A1992JZ61700005 PM 19912894 ER PT J AU MAR, EC SUH, HH HONG, JS AF MAR, EC SUH, HH HONG, JS TI REGULATION OF PROENKEPHALIN EXPRESSION IN C6 RAT GLIOMA-CELLS SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID PREPROENKEPHALIN MESSENGER-RNA; TRANSCRIPTION FACTOR AP-1; ADRENAL CHROMAFFIN CELLS; T-HELPER CELLS; ENKEPHALIN BIOSYNTHESIS; CYCLIC-AMP; INDUCIBLE ENHANCER; RECEPTOR GENE; PROTEINS; GLUCOCORTICOIDS C1 UNIV N CAROLINA,SCH MED,LINEBERGER COMPREHENS CANC RES CTR,CHAPEL HILL,NC 27599. RP MAR, EC (reprint author), NIEHS,NEUROPHARMACOL SECT,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709, USA. NR 50 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD DEC PY 1992 VL 3 IS 6 BP 518 EP 528 DI 10.1016/1044-7431(92)90064-9 PG 11 WC Neurosciences SC Neurosciences & Neurology GA JZ617 UT WOS:A1992JZ61700006 PM 19912895 ER PT J AU GREGOR, P YANG, XD MANO, I TAKEMURA, M TEICHBERG, VI UHL, GR AF GREGOR, P YANG, XD MANO, I TAKEMURA, M TEICHBERG, VI UHL, GR TI ORGANIZATION AND EXPRESSION OF THE GENE ENCODING CHICK KAINATE BINDING-PROTEIN, A MEMBER OF THE GLUTAMATE RECEPTOR FAMILY SO MOLECULAR BRAIN RESEARCH LA English DT Article DE KAINATE RECEPTOR GENE; BERGMANN GLIA; CEREBELLUM; GENE STRUCTURE ID NICOTINIC ACETYLCHOLINE-RECEPTOR; CENTRAL-NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; FUNCTIONAL EXPRESSION; XENOPUS OOCYTES; SUBUNIT; CLONING; CHANNELS; BRAIN; DNA AB The gene encoding chick cerebellar Bergmann glia-specific kainate binding protein (chKBP), has been isolated, characterized and expressed in heterologous systems. The structural gene spans 11.2 kb and contains 11 exons and 10 introns. Several of the exons encode specific receptor domains, including each of the predicted transmembrane regions. Exon/intron boundaries flanking the second, putative channel-forming transmembrane domain are conserved between chKBP and other glutamate/kainate receptor subunits. The putative promoter region 5' to the first exon displays high GC content and TATA, CAAT and AP1 consensus sequences. Transcription of the chKBP gene is evident prior to full cerebellar cortical maturation. Transcripts are abundant in cells consistent with Bergmann glia, as revealed by in situ hybridization. Transfection of 293 kidney cell cultures with chKBP cDNA or chKBP gene expression constructs confers CNQX-sensitive kainate binding with the pharmacological specificity displayed by both chKBP and kainate receptors. However, expression of the same constructs in Xenopus oocytes fails to yield detectable agonist-activated currents. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. WEIZMANN INST SCI,DEPT NEUROBIOL,IL-76100 REHOVOT,ISRAEL. RP GREGOR, P (reprint author), NIDA,MOLEC NEUROBIOL LAB,POB 5180,BALTIMORE,MD 21224, USA. NR 47 TC 17 Z9 17 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 DEC PY 1992 VL 16 IS 3-4 BP 179 EP 186 DI 10.1016/0169-328X(92)90223-X PG 8 WC Neurosciences SC Neurosciences & Neurology GA KG896 UT WOS:A1992KG89600001 ER PT J AU UHL, GR KITAYAMA, S GREGOR, P NANTHAKUMAR, E PERSICO, A SHIMADA, S AF UHL, GR KITAYAMA, S GREGOR, P NANTHAKUMAR, E PERSICO, A SHIMADA, S TI NEUROTRANSMITTER TRANSPORTER FAMILY CDNAS IN A RAT MIDBRAIN LIBRARY - ORPHAN TRANSPORTERS SUGGEST SIZABLE STRUCTURAL VARIATIONS SO MOLECULAR BRAIN RESEARCH LA English DT Note DE ORPHAN TRANSPORTER; MIDBRAIN; RAT ID CENTRAL NERVOUS-SYSTEM; DOPAMINE TRANSPORTER; EXPRESSION; CLONING; BRAIN AB Assessment of neurotransmitter transporter family cDNAs in a size-selected rat ventral midbrain cDNA library suggests that this family is unexpectedly diverse and defines the sequence of an interesting 'orphan' member of this family. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RP UHL, GR (reprint author), NIDA,MOLEC NEUROBIOL LAB,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 26 TC 49 Z9 50 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 DEC PY 1992 VL 16 IS 3-4 BP 353 EP 359 DI 10.1016/0169-328X(92)90246-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA KG896 UT WOS:A1992KG89600024 ER PT J AU OOI, GT TSENG, LYH TRAN, MQ RECHLER, MM AF OOI, GT TSENG, LYH TRAN, MQ RECHLER, MM TI INSULIN RAPIDLY DECREASES INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 GENE-TRANSCRIPTION IN STREPTOZOTOCIN-DIABETIC RATS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HEPATOMA-CELLS; HORMONAL-REGULATION; PHORBOL ESTERS; MESSENGER-RNA; GLUCAGON GENE; PEPCK GENE; IGF-I; EXPRESSION; LIVER; SEQUENCE AB Insulin-like growth factor-binding protein-1 (IGFBP-1) can inhibit or potentiate IGF action. The biological activity of IGFBP-1 is determined by many factors, including its abundance in tissues and plasma, posttranslational modifications, and localization. IGFBP-1 levels in human plasma are highly regulated. They are increased after acute fasting and in diabetes, and are rapidly reversed by refeeding and insulin treatment, respectively. Similarly, IGFBP-1 mRNA is increased in the liver of severely diabetic and ketotic rats and decreased after 4 days of insulin treatment. Insulin rapidly decreases IGFBP-1 mRNA and IGFBP-1 transcription in rat hepatoma cells. The present study asks whether the increase in IGFBP-1 mRNA in diabetic rat liver reflects increased gene transcription, whether insulin decreases IGFBP-1 mRNA through a transcriptional or posttranscriptional mechanism, and whether this decrease is sufficiently rapid to account for the dynamic fluctuations in plasma IGFBP-1. Rats were injected ip with 100 mg/kg streptozotocin and used 7 days later when they were hyperglycemic and failed to gain weight, but were not ketotic. Hepatic IGFBP-1 mRNA levels were 13.6 +/- 5.3-fold greater in diabetic than control liver and decreased to the low levels in nondiabetic controls within 1 h after insulin treatment. In run-on transcription assays, IGFBP-1 transcription was 12.6 +/- 1.5-fold greater in nuclei from diabetic than control liver and decreased to low control levels by 1 h after insulin injection. Normalization of hepatic IGFBP-1 mRNA in insulin-treated diabetic animals did not require restoration of euglycemia. IGFBP-1 mRNA and IGFBP-1 gene transcription also were increased in the kidney of diabetic ketotic rats. We propose that the dynamic regulation of IGFBP-1 gene transcription in diabetes and after insulin treatment, by determining the availability of IGFBP-1 in tissues and plasma, may be a critical factor in the modulation of IGF action. RP OOI, GT (reprint author), NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, GROWTH & DEV SECT, BLDG 10, ROOM 8D14, BETHESDA, MD 20892 USA. NR 59 TC 86 Z9 89 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1992 VL 6 IS 12 BP 2219 EP 2228 DI 10.1210/me.6.12.2219 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KE801 UT WOS:A1992KE80100025 PM 1283442 ER PT J AU OCARROLL, AM LOLAIT, SJ KONIG, M MAHAN, LC AF OCARROLL, AM LOLAIT, SJ KONIG, M MAHAN, LC TI MOLECULAR-CLONING AND EXPRESSION OF A PITUITARY SOMATOSTATIN RECEPTOR WITH PREFERENTIAL AFFINITY FOR SOMATOSTATIN-28 SO MOLECULAR PHARMACOLOGY LA English DT Note ID RAT ANTERIOR-PITUITARY; TRANSDUCTION MECHANISMS; MAMMALIAN-CELLS; CEREBRAL-CORTEX; SUBTYPES; BINDING; BRAIN; MEMBRANES; ANALOGS; NEURONS AB Using the polymerase chain reaction technique with degenerative primers, we obtained from a rat pituitary cDNA library a cDNA fragment, rAP236, that exhibited considerable homology to known receptors that belong to the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. Oligonucleotides to this fragment were used as probes to obtain a full-length cDNA from the rat pituitary cDNA library. This clone, rAP6-26, encoded a 383-amino acid protein with seven putative transmembrane domains that are characteristic of G protein-coupled receptors. The predicted amino acid sequence of the rAP6-26 cDNA exhibits 56-66% homology to recently cloned somatostatin (SRIF) receptors. Membranes prepared from COS-7 cells transfected with the rAP6-26 cDNA showed specific binding of I-125-Tyr11-SRIF, thus identifying the cDNA clone as a novel SRIF receptor. Radioligand binding competition analysis using somatostatin-28 (SRIF-28) and a number of cyclic SRIF analogs revealed that SRIF-28 was the most potent competitor of I-125 Tyr11-SRIF binding, with a approximately 30-fold greater affinity for the receptor than that of SRIF. In addition, binding of I-125-Tyr11-SRIF was markedly reduced in the presence of Na+ ions and GTP, indicating coupling of rAP6-26 receptors to inhibitory G proteins in COS-7 membranes. In adenylyl cyclase assays, forskolin-induced cAMP accumulation was inhibited by SRIF and SRIF-28, thus confirming that the rAP6-26 cDNA encodes a functional receptor protein. By Northern blot analysis, a -2.6 kilobase mRNA encoding the receptor was present in the pituitary but not in the liver, small intestine, kidney, pancreas, cerebellum, or cortex. Lack of receptor mRNA expression in the brain was confirmed by in situ hybridization histochemical studies. Thus, we report the cloning of a novel rat pituitary SRIF receptor, termed SSTR4, that has marked preferential affinity for SRIF-28 and is linked to inhibition of adenylyl cyclase. RP OCARROLL, AM (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A 17,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 39 TC 301 Z9 303 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1992 VL 42 IS 6 BP 939 EP 946 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KD856 UT WOS:A1992KD85600001 PM 1362243 ER PT J AU WONG, G SEI, Y SKOLNICK, P AF WONG, G SEI, Y SKOLNICK, P TI STABLE EXPRESSION OF TYPE-1 GAMMA-AMINOBUTYRIC ACID(A) BENZODIAZEPINE RECEPTORS IN A TRANSFECTED CELL-LINE SO MOLECULAR PHARMACOLOGY LA English DT Article ID GABA-A RECEPTORS; CHLORIDE CHANNEL COMPLEX; RAT-BRAIN; SUBUNIT COMPOSITION; ALCOHOL ANTAGONIST; MOLECULAR-BIOLOGY; BINDING; PHARMACOLOGY; INCREASES; ANXIETY AB Expression plasmids were constructed with cDNAs encoding the rat gamma-aminobutyric acid-A (GABA(A)) receptor alpha1, beta2, and gamma2 subunits and were cotransfected into cultured human embryonic kidney 293 cells. A single cell line (WS-1) was established after G-418 treatment and clonal selection. This cell line contained saturable, high affinity binding sites for the benzodiazepines [H-3] Ro 15-4513 and [H-3]flunitrazepam that were modulated by GABA. Competition experiments with benzodiazepine receptor ligands suggest a profile characteristic of native ''type I'' benzodiazepine receptors, because strong correlations were observed between the K(i) values of these ligands in WS-1 cells and in both cerebellar homogenates (r = 0.97, p < 0.0001) and 293 cells transiently transfected with the corresponding cDNAs (r = 0.96, p < 0.001). Fluorescence intensity in WS-1 cells loaded with the Cl--specific probe 6-methoxy-N-(3-sulfopropyl)-quinolinium was reliably increased by GABA. This effect was blocked by bicuculline and augmented by midazolam, consistent with the presence of GABA-gated, benzodiazepine receptor-modulated, Cl- channels. Northern blot analysis revealed the presence of mRNAs encoding alpha1 and gamma2 receptor subunits. Southern blot analysis confirmed genomic integration of transfected alpha1 and gamma2 cDNAs. The beta2 subunit was not detected in either Northern or Southern blot analysis, indicating that a functional type I GABA(A)/benzodiazepine receptor complex can be constituted without a beta subunit. RP WONG, G (reprint author), NIDDKD,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 39 TC 66 Z9 66 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1992 VL 42 IS 6 BP 996 EP 1003 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KD856 UT WOS:A1992KD85600009 PM 1336119 ER PT J AU AHMAD, S TREPEL, JB OHNO, S SUZUKI, K TSURUO, T GLAZER, RI AF AHMAD, S TREPEL, JB OHNO, S SUZUKI, K TSURUO, T GLAZER, RI TI ROLE OF PROTEIN-KINASE-C IN THE MODULATION OF MULTIDRUG RESISTANCE - EXPRESSION OF THE ATYPICAL GAMMA-ISOFORM OF PROTEIN-KINASE-C DOES NOT CONFER INCREASED RESISTANCE TO DOXORUBICIN SO MOLECULAR PHARMACOLOGY LA English DT Article ID PLASMA-MEMBRANE GLYCOPROTEIN; KB CARCINOMA-CELLS; BACTERIAL TRANSPORT PROTEINS; MULTIPLE-DRUG RESISTANCE; DNA-MEDIATED TRANSFER; HL-60 LEUKEMIA-CELLS; BREAST CANCER-CELLS; HUMAN MDR1 GENE; P-GLYCOPROTEIN; DIFFERENTIAL EXPRESSION AB Cross-resistance to anticancer drugs, termed multidrug resistance (MDR), is functionally associated with the expression of a plasma membrane, energy-dependent, drug efflux pump termed P-glycoprotein (PGP), the product of the mdr1 gene. We have shown previously that MCF-7 breast carcinoma cells transfected with the human mdr1 gene (BC-19 cells) exhibit greater MDR when stably transfected with protein kinase Calpha (PKCalpha). We now demonstrate that transfection of BC-1 9 cells with the gamma isoform of PKC (BC-19/PKCgamma cells), which is not normally present in BC-19 cells, does not confer increased resistance to doxorubicin, despite a 19-fold increase in PKC activity. All of the increased PKC activity is accounted for by PKCgamma and it is rapidly down-regulated by phorbol dibutyrate, within 15 min of treatment. Endogenous PKCalpha and PKCepsilon activities are not affected by phorbol dibutyrate. The cytotoxicity of doxorubicin was similar in BC-19/neo or BC-19/PKCgamma cells after either 2-hr or continuous drug exposure, and co-treatment with phorbol dibutyrate increased resistance to doxorubicin 4-fold in both cell lines. Phosphorylation of PGP was similar in both cell lines and drug accumulation was not affected by overexpression of PKCgamma. These results demonstrate that transfection of PGP-expressing cells with an atypical isoform of PKC does not confer increased MDR, and they suggest that the regulation of PGP is phenotype specific with respect to the isoform of PKC. C1 GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NCI,MED BRANCH,BETHESDA,MD 20892. YOKOHAMA CITY UNIV,SCH MED,DEPT MOLEC BIOL,YOKOHAMA 236,JAPAN. JAPANESE FDN CANC RES,TOKYO 170,JAPAN. RI Ohno, Shigeo/B-1768-2010 OI Ohno, Shigeo/0000-0002-1294-5269 NR 54 TC 40 Z9 41 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1992 VL 42 IS 6 BP 1004 EP 1009 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KD856 UT WOS:A1992KD85600010 PM 1362242 ER PT J AU BENYA, RV WADA, E BATTEY, JF FATHI, Z WANG, LH MANTEY, SA COY, DH JENSEN, RT AF BENYA, RV WADA, E BATTEY, JF FATHI, Z WANG, LH MANTEY, SA COY, DH JENSEN, RT TI NEUROMEDIN-B RECEPTORS RETAIN FUNCTIONAL EXPRESSION WHEN TRANSFECTED INTO BALB 3T3 FIBROBLASTS - ANALYSIS OF BINDING, KINETICS, STOICHIOMETRY, MODULATION BY GUANINE NUCLEOTIDE-BINDING PROTEINS, AND SIGNAL TRANSDUCTION AND COMPARISON WITH NATIVELY EXPRESSED RECEPTORS SO MOLECULAR PHARMACOLOGY LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; GASTRIN-RELEASING PEPTIDE; BOMBESIN-LIKE PEPTIDES; RAT PANCREATIC ACINI; SMOOTH-MUSCLE CELLS; LIGAND-BINDING; HIGH-AFFINITY; CHICK HEART; MEDIATED ENDOCYTOSIS; INOSITOL PHOSPHATES AB The receptor that interacts with the mammalian bombesin-related peptide neuromedin B (NMB) is ubiquitous in the gastrointestinal tract and central nervous system. However, little is known regarding its cellular mechanisms of action. This receptor has been recently cloned, sequenced, and stably transfected into BALB 3T3 fibroblasts, permitting detailed study of the pharmacology and coupled biological activities of this receptor. In the present study, we compare the ability of transfected receptors to alter cell function with that of receptors natively expressed in small numbers by the rat glioblastoma cell line C6. NMB inhibited binding of I-125-[D-Tyr0]NMB with high affinity in transfected cells (K(j) = 3.08 +/- 0.14 nm) and in C6 cells (K(j) = 1.90 +/- 1.10 nm), whereas the bombesin-related agonists gastrin-releasing peptide (GRP) and [D-Phe6, D-Ala11, Leu14]bombesin(6-16) (GRP analogue) had 100- and 300-fold lower affinities, respectively, for NMB receptors in either cell type. For both cell systems, maximal binding was observed between 5 and 15 min at 22-degrees. Both cell types internalized NMB at similar rates, with >70% of bound ligand being internalized by 60 min at 22-degrees. The nonhydrolyzable guanosine analogue guanosine 5'-(beta,gamma-imido)triphosphate was equipotent in causing a decrease in binding of I-125-[D-Tyr0]NMB due to decreased receptor affinity in both cell types, without a change in receptor number, demonstrating that the NMB receptor remained coupled to a guanine nucleotide-binding protein in both native and transfected cells. In both cell systems, NMB increased inositol monophosphate, inositol bisphosphate, and inositol trisphosphate in a time-dependent fashion. Inositol phosphates were increased in a dose-dependent fashion, with similar haff-maximal values being obtained for NMB in both cell types (transfected, 1.01 +/- 0.09 nm; C6, 2.09 +/- 0.15 nm) and for the GRP analogue (transfected, 1855 +/- 140 nm; C6, 2129 +/- 250 nm). NMB mobilized intracellular Ca2+ in both cell systems, and the dose-response curves were superimposible (EC50 for transfected, 0.10 +/- 0.08 nm; C6, 0.11 +/- 0.02 nm). These data demonstrate that activation of the receptor for NMB stimulates phospholipase C and increases intracellular Ca2+. These results also demonstrate that transfected and native NMB receptors behave similarly, suggesting that the transfected cell line will be useful in future studies investigating ligand-receptor interactions, as well as in molecular biological studies of the structure-function relationship of the receptor. C1 NIDDKD,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892. NCI,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892. TULANE UNIV,PEPTIDE RES LAB,NEW ORLEANS,LA 70117. NR 58 TC 66 Z9 67 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1992 VL 42 IS 6 BP 1058 EP 1068 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KD856 UT WOS:A1992KD85600018 PM 1336112 ER PT J AU GUSOVSKY, F PADGETT, WL CREVELING, CR DALY, JW AF GUSOVSKY, F PADGETT, WL CREVELING, CR DALY, JW TI INTERACTION OF PUMILIOTOXIN-B WITH AN ALKALOID-BINDING DOMAIN ON THE VOLTAGE-DEPENDENT SODIUM-CHANNEL SO MOLECULAR PHARMACOLOGY LA English DT Article ID NERVE-ENDING PARTICLES; SYNAPTONEUROSOMES; TETRODOTOXIN; NEUROTOXINS; PYRETHROIDS; ACTIVATION; SCORPION; AGENTS; TOXINS; SITES AB The alkaloid pumiliotoxin B (PTX-B) ''activates'' voltage-dependent sodium channels in synaptoneurosomes and neuroblastoma cells. It appears that PTX-B activates sodium channels by interacting with a site that is allosterically coupled to other sites on the sodium channel, namely two scorpion toxin sites and the brevetoxin site. In guinea pig cortical synaptoneurosomes, alpha-scorpion toxin, beta-scorpion toxin, and brevetoxin induce a dose-dependent potentiation of PTX-B-induced Na-22(+) influx. The synergism with beta-scorpion toxin differentiates PTX-B from the alkaloid veratridine, which induces an activation of sodium channels that is not affected by beta-scorpion toxin. PTX-B does not inhibit [H-3]batrachotoxinin-A benzoate ([H-3]BTX-B) binding to the alkaloid site on sodium channels. On the other hand, aconitine, which activates sodium channels and inhibits [H-3]BTX-B binding, induces a Na-22(+) influx that, like PTX-B-induced Na-22(+) influx, is potentiated by alpha-scorpion toxin, beta-scorpion toxin, and brevetoxin. Inhibition of [H-3]BTX-B binding by aconitine is reduced in the presence of PTX-B. Both a type I pyrethroid (allethrin) and a type II pyrethroid (fenvalerate) inhibit PTX-B- and PTX-B/alpha-scorpion toxin-mediated Na-22(+) influx. Allethrin and fenvalerate also inhibit aconitine-mediated Na-22(+) flux but not BTX-mediated Na-22(+) influx. It is proposed that on the sodium channel there is an ''alkaloid-binding domain'' at which alkaloids exert stimulatory actions. However, depending on the region on the domain to which the binding occurs, different allosteric interactions with other sites can be observed. PTX-B is proposed to interact with a part of the alkaloid-binding domain that is shared by aconitine but not by batrachotoxin or veratridine, whereas aconitine interacts with a part of the domain shared by PTX-B and by batrachotoxin/veratridine. RP GUSOVSKY, F (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8,ROOM 1A-15,BETHESDA,MD 20892, USA. NR 21 TC 20 Z9 21 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1992 VL 42 IS 6 BP 1104 EP 1108 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KD856 UT WOS:A1992KD85600024 PM 1336116 ER PT J AU QU, YH XU, GX ZHOU, JZ CHEN, TD ZHU, LF SHIELDS, PG WANG, HW GAO, YT AF QU, YH XU, GX ZHOU, JZ CHEN, TD ZHU, LF SHIELDS, PG WANG, HW GAO, YT TI GENOTOXICITY OF HEATED COOKING OIL VAPORS SO MUTATION RESEARCH LA English DT Article DE COOKING OIL VAPORS; HEATED; LUNG CANCER; CHINESE WOMEN; RAPESEED COOKING OIL; SOYBEAN COOKING OIL ID LUNG-CANCER; MUTAGENS; WOMEN AB Epidemiological studies of lung cancer in Chinese women indicated that factors other than cigarette smoking are related to lung cancer risk. A case-control study suggested that indoor air pollution, particularly from cooking oil emissions, may be involved. Condensates of volatile emissions from rapeseed and soybean cooking oils were prepared and found to be genotoxic in short-term tests including the Salmonella mutation assay, SV50 forward-mutation assay, and sister-chromatid exchange assay, as well as the micronucleus assay in mouse bone marrow. In contrast, condensates from rapeseed oil with butylated hydroxyanisole or hydrogenated rapeseed oil were not mutagenic, implicating oxidation products as the cause for mutagenicity. Peanut oil and lard condensates were not mutagenic in any assay. The association of exposure to Chinese rapeseed cooking-oil emissions and lung-cancer risk may be related to the mutagenic component of these condensates. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C16,BETHESDA,MD 20892. SHANGHAI CANC INST,SHANGHAI 20032,PEOPLES R CHINA. ACAD SINICA,SHANGHAI INST CELL BIOL,SHANGHAI 200032,PEOPLES R CHINA. RI Shields, Peter/I-1644-2012 NR 13 TC 64 Z9 73 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD DEC PY 1992 VL 298 IS 2 BP 105 EP 111 DI 10.1016/0165-1218(92)90035-X PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA JZ777 UT WOS:A1992JZ77700006 PM 1282206 ER PT J AU DELLARCO, VL SHELBY, MD AF DELLARCO, VL SHELBY, MD TI SPECIAL ISSUE - FEMALE GERM-CELLS - BIOLOGY AND GENETIC RISK - EDITORIAL INTRODUCTION SO MUTATION RESEARCH LA English DT Editorial Material C1 NIEHS,RES TRIANGLE PK,NC 27709. RP DELLARCO, VL (reprint author), US EPA,OHEA,HHAG RD689,401 M ST SW,WASHINGTON,DC 20460, USA. NR 0 TC 7 Z9 7 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 DEC PY 1992 VL 296 IS 1-2 BP 1 EP 1 DI 10.1016/0165-1110(92)90027-7 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA JZ006 UT WOS:A1992JZ00600001 ER PT J AU LEWIS, SE BARNETT, LB SHELBY, MD AF LEWIS, SE BARNETT, LB SHELBY, MD TI ENU MUTAGENESIS IN THE MOUSE ELECTROPHORETIC SPECIFIC-LOCUS TEST .2. MUTATIONAL STUDIES OF MATURE OOCYTES SO MUTATION RESEARCH LA English DT Article DE OOCYTE; ETHYL NITROSOUREA; ELECTROPHORETIC MUTATION SCREENING SYSTEM; GERM CELLS ID FEMALE MICE; ETHYLNITROSOUREA; RADIATION; INDUCTION; PROCARBAZINE; MODEL AB Experiments were conducted using the biochemical specific-locus test to assess the mutagenicity of N-ethyl-N-nitrosourea (ENU) in mature oocytes of mice. C57Bl/6J females were treated with 100 mg/kg ENU by intraperitoneal injection and mated to untreated DBA males for 1 week following treatment. 1447 progeny were screened for evidence of mutations affecting the electrophoretic mobility of 32 different proteins; two mutants were detected by electrophoretic analyses. These results provide evidence that ENU is a germ-cell mutagen in mouse mature oocytes, although the frequency of mutants is somewhat lower than that obtained from spermatogonia treated with the same dose. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP LEWIS, SE (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. NR 30 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD DEC PY 1992 VL 296 IS 1-2 BP 129 EP 133 DI 10.1016/0165-1110(92)90036-9 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA JZ006 UT WOS:A1992JZ00600010 PM 1279399 ER PT J AU SUDMAN, PD RUTLEDGE, JC BISHOP, JB GENEROSO, WM AF SUDMAN, PD RUTLEDGE, JC BISHOP, JB GENEROSO, WM TI BLEOMYCIN - FEMALE-SPECIFIC DOMINANT LETHAL EFFECTS IN MICE SO MUTATION RESEARCH LA English DT Article DE MOUSE; OOCYTE; CHROMOSOMAL ABERRATION; DOMINANT LETHAL; REPRODUCTIVE EFFECTS; BLEOMYCIN ID FRAGILE SITES; DNA; CHROMOSOME; CANCER AB Limited comparative data in mice indicate that chemical mutagens that induce dominant lethal mutations in males are not necessarily effective in females, but those which are effective in females are generally equally or more effective in males. Recently, however, a few chemicals have been identified that are female-specific with respect to induction of dominant lethal mutations. The antitumor antibiotic adriamycin is among them. Another antitumor antibiotic, bleomycin was examined for its ability to induce dominant lethal mutations in the reproductive cells of male and female mice. No dominant lethal or cytotoxic effects were observed in males treated with bleomycin, even at a maximum tolerated dose. In females, on the other hand, a dose nearly 1/4 of that used in males induced not only a high level of dominant lethal mutations but also killed oocytes in certain stages of follicular development. The effectiveness of bleomycin in inducing dominant lethal mutations in mouse oocytes makes it a valuable tool for investigating whether gonadal transport, inherent differences in the configuration of chromatin in the germ cells of the two sexes or other factors are responsible for the differential susceptibility to bleomycin, which implies potential gender-specific genetic risk in cancer chemotherapy. C1 OAK RIDGE NATL LAB,DIV BIOL,POB 2009,OAK RIDGE,TN 37831. UNIV TENNESSEE,OAK RIDGE GRAD SCH BIOMED SCI,OAK RIDGE,TN 37830. UNIV WASHINGTON,CHILDRENS HOSP,SCH MED,DEPT LAB MED,SEATTLE,WA 98105. NIEHS,CELLULAR & GENET TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [Y01-ES-20085] NR 29 TC 26 Z9 27 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 DEC PY 1992 VL 296 IS 1-2 BP 143 EP 156 DI 10.1016/0165-1110(92)90038-B PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA JZ006 UT WOS:A1992JZ00600012 PM 1279401 ER PT J AU KOONIN, EV WOODS, DF BRYANT, PJ AF KOONIN, EV WOODS, DF BRYANT, PJ TI DLG-R PROTEINS - MODIFIED GUANYLATE KINASES SO NATURE GENETICS LA English DT Letter ID BINDING PROTEINS; SEQUENCE; MOTIF; CLONING C1 UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92717. RP KOONIN, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 23 TC 20 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1992 VL 2 IS 4 BP 256 EP 257 DI 10.1038/ng1292-256 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA KB495 UT WOS:A1992KB49500006 PM 1338911 ER PT J AU LEFF, SE BRANNAN, CI REED, ML OZCELIK, T FRANCKE, U COPELAND, NG JENKINS, NA AF LEFF, SE BRANNAN, CI REED, ML OZCELIK, T FRANCKE, U COPELAND, NG JENKINS, NA TI MATERNAL IMPRINTING OF THE MOUSE SNRPN GENE AND CONSERVED LINKAGE HOMOLOGY WITH THE HUMAN PRADER-WILLI SYNDROME REGION SO NATURE GENETICS LA English DT Article ID CALCITONIN GENE; CDNA; RIBONUCLEOPROTEIN; CHROMOSOME-7; EXPRESSION; RECEPTOR; NEUROPEPTIDE; ANTIBODIES; PROTEINS; SUBUNIT AB Prader-Willi syndrome (PWS) is associated with paternal gene deficiencies in human chromosome 1511-13, suggesting that PWS is caused by a deficiency in one or more maternally imprinted genes. We have now mapped a gene, Snrpn, encoding a brain-enriched small nuclear ribonucleoprotein (snRNP)-associated polypeptide SmN, to mouse chromosome 7 in a region of homology with human chromosome 1511-13 and demonstrated that Snrpn is a maternally imprinted gene in mouse. These studies, in combination with the accompanying human mapping studies showing that SNRPN maps in the Prader-Willi critical region, identify SNRPN as a candidate gene involved in PWS and suggest that PWS may be caused, in part, by defects in mRNA processing. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. STANFORD UNIV,MED CTR,SCH MED,HOWARD HUGHES MED INST,STANFORD,CA 94305. STANFORD UNIV,MED CTR,SCH MED,DEPT GENET & PEDIAT,STANFORD,CA 94305. RP LEFF, SE (reprint author), STANFORD UNIV,MED CTR,SCH MED,DEPT PHARMACOL,STANFORD,CA 94305, USA. FU NCI NIH HHS [N01-CO-74101] NR 52 TC 239 Z9 243 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1992 VL 2 IS 4 BP 259 EP 264 DI 10.1038/ng1292-259 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA KB495 UT WOS:A1992KB49500007 PM 1303276 ER PT J AU CATTANACH, BM BARR, JA EVANS, EP BURTENSHAW, M BEECHEY, CV LEFF, SE BRANNAN, CI COPELAND, NG JENKINS, NA JONES, J AF CATTANACH, BM BARR, JA EVANS, EP BURTENSHAW, M BEECHEY, CV LEFF, SE BRANNAN, CI COPELAND, NG JENKINS, NA JONES, J TI A CANDIDATE MOUSE MODEL FOR PRADER-WILLI SYNDROME WHICH SHOWS AN ABSENCE OF SNRPN EXPRESSION SO NATURE GENETICS LA English DT Article ID ANGELMAN SYNDROME; PARENTAL ORIGIN; CHROMOSOME-15 DELETION; 15Q DELETIONS; GENE; REGION; 15Q11-13; RECEPTOR; SUBUNIT; RNA AB The best examples of imprinting in humans are provided by the Angelman and Prader-Willi syndromes (AS and PWS) which are associated with maternal and paternal 15q11-13 deletions, respectively, and also with paternal and maternal disomy 15. The region of the deletions has homology with a central part of mouse chromosome 7, incompletely tested for imprinting effects. Here, we report that maternal duplication for this region causes a murine imprinting effect which may correspond to PWS. Paternal duplication was not associated with any detectable effect that might correspond with AS. Gene expression studies established that Snrpn is not expressed in mice with the maternal duplication and suggest that the closely-linked Gabrb-3 locus is not subject to imprinting. Flnally, an additional new imprinting effect is described. C1 STANFORD UNIV,MED CTR,SCH MED,DEPT PHARMACOL,STANFORD,CA 94305. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP CATTANACH, BM (reprint author), MRC,RADIOBIOL UNIT,DIV GENET,DIDCOT OX11 0RD,OXON,ENGLAND. NR 38 TC 156 Z9 156 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1992 VL 2 IS 4 BP 270 EP 274 DI 10.1038/ng1292-270 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA KB495 UT WOS:A1992KB49500009 PM 1303278 ER PT J AU AKUNNE, HC DECOSTA, BR JACOBSON, AE RICE, KC ROTHMAN, RB AF AKUNNE, HC DECOSTA, BR JACOBSON, AE RICE, KC ROTHMAN, RB TI [H-3] COCAINE LABELS A BINDING-SITE ASSOCIATED WITH THE SEROTONIN TRANSPORTER IN GUINEA-PIG BRAIN - ALLOSTERIC MODULATION BY PAROXETINE SO NEUROCHEMICAL RESEARCH LA English DT Article DE COCAINE; PAROXETINE; SEROTONIN; SEROTONIN UPTAKE; GBR12909 ID COCAINE BINDING; DOPAMINE UPTAKE; RAT-BRAIN; -LABELED COCAINE; NUCLEUS-ACCUMBENS; MOUSE-BRAIN; RELEASE; INHIBITORS; RECEPTORS; STRIATUM AB We studied the characteristics of [H-3]cocaine binding to membranes prepared from whole guinea pig brain. Cocaine binding was specific and saturable. A one-site binding model fit the data adequately: the Kd value of [H-3]cocaine was 44 nM with a Bmax value of 280 fmol/mg protein. The rank order of potency for the [H-3]cocaine binding site was paroxetine > clomipramine > (-)-cocaine > fluoxetine > mazindol > desipramine> GBR12909 > phencyclidine > benztropine > GBR12935 > (+)-cocaine. The IC50 values of these drugs for inhibition of [H-3]cocaine binding were highly correlated with their IC50 values for inhibition of [H-3]5-HT uptake into synaptosomes prepared from whole guinea pig brain. High affinity 5-HT uptake inhibitors produced dose-dependent wash-resistant (pseudoirreversible) inhibition of [H-3]cocaine binding. The wash-resistant inhibition produced by paroxetine was due to an increase in the Kd of [H-3]cocaine binding sites, and was accompanied by an increase in the dissociation rate, consistent with an allosteric mechanism. These studies suggest that, using membranes prepared from whole guinea pig brain, [H-3]cocaine labels a binding site associated with serotonin transporter and that paroxetine and cocaine bind to different sites on the serotonin transporter. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL LAB,POB 5180,BALTIMORE,MD 21224. NIDDKD,MED CHEM LAB,DRUG DESIGN & SYNTH SECT,BETHESDA,MD 20892. NR 31 TC 31 Z9 31 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD DEC PY 1992 VL 17 IS 12 BP 1275 EP 1283 DI 10.1007/BF00968412 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JX296 UT WOS:A1992JX29600018 PM 1461373 ER PT J AU LIN, WW CHUANG, DM AF LIN, WW CHUANG, DM TI REGULATION OF BRADYKININ-INDUCED PHOSPHOINOSITIDE TURNOVER IN CULTURED CEREBELLAR ASTROCYTES - POSSIBLE ROLE OF PROTEIN-KINASE-C SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID INOSITOL PHOSPHOLIPID HYDROLYSIS; STIMULATED POLYPHOSPHOINOSITIDE HYDROLYSIS; EXCITATORY AMINO-ACIDS; GLIOMA HYBRID-CELLS; SMOOTH-MUSCLE CELLS; PERTUSSIS TOXIN; DOWN-REGULATION; NG108-15 CELLS; GRANULE CELLS; NCB-20 CELLS AB Phosphoinositide hydrolysis was studied in primary cultures of rat cerebellar astrocytes prelabeled with [H-3]myo-inositol. Among the agonists examined, the rank order of efficacies in causing phosphoinositide hydrolysis was bradykinin > endothelin-1 > ATP > norepinephrine. The bradykinin response was robust (24-fold increase) with EC50 value of 30 nM and saturating concentration of 1 muM. Preincubation of cells with pertussis toxin did not affect the activation of phosphoinositide turnover by bradykinin. Although short-term (within 90 min) treatment of cells with phorbol dibutyrate attenuated bradykinin-induced phosphoinositide breakdown, the inhibitory effect was lost after 3-6 h of phorbol dibutyrate treatment. Extended (24 h) preincubation resulted in a potentiation of bradykinin response. Homologous desensitization of bradykinin response was observed in cells prestimulated with bradykinin for up to 6 h. However, similar to the effect of phorbol dibutyrate, 24-h pretreatment with bradykinin selectively sensitized the response to bradykinin. Up-regulation of the bradykinin response was also observed in cells prestimulated with endothelin-I or norepinephrine for 24 h, although these treatments resulted in only homologous desensitization to their own response. Our results suggest that cultured cerebellar astrocytes express bradykinin receptors coupled to phospholipase C and in these cells protein kinase C plays a more prominent role in the negative-feedback regulation of bradykinin-evoked phosphoinositide response. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BLDG 10,RM 3N212,BETHESDA,MD 20892. NATL TAIWAN UNIV,COLL MED,DEPT PHARMACOL,TAIPEI,TAIWAN. OI Lin, Wan Wan/0000-0002-3207-734X NR 38 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD DEC PY 1992 VL 21 IS 4 BP 573 EP 579 DI 10.1016/0197-0186(92)90090-E PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JY730 UT WOS:A1992JY73000011 PM 1338944 ER PT J AU VISWANATHAN, M LAITINEN, JT SAAVEDRA, JM AF VISWANATHAN, M LAITINEN, JT SAAVEDRA, JM TI DIFFERENTIAL EXPRESSION OF MELATONIN RECEPTORS IN SPONTANEOUSLY HYPERTENSIVE RATS SO NEUROENDOCRINOLOGY LA English DT Article DE QUANTITATIVE AUTORADIOGRAPHY; I-[I-125]-IODOMELATONIN; ANTERIOR CEREBRAL ARTERY; CAUDAL ARTERY; AREA POSTREMA; SUPRACHIASMATIC NUCLEI; THERMOREGULATION ID AREA POSTREMA; GUANINE-NUCLEOTIDES; BLOOD-PRESSURE; TEMPERATURE; PINEAL; THERMOREGULATION; MODULATION; AFFINITY; CATIONS; STRESS AB Quantitative autoradiography was used to compare melatonin receptors in brain areas and arteries of young (4 weeks old) and adult (14 weeks old) spontaneously hypertensive rats (SHR) to those in age-matched normotensive controls, Wistar-Kyoto (WKY) rats. Age and strain influenced the number of melatonin receptors in an anatomically selective manner, and the most striking changes occurred in arterial receptors. Melatonin receptors were not detectable in the anterior cerebral arteries of adult SHR. In the caudal artery, melatonin receptors decreased with age in both strains, but the decrease was more pronounced in SHR. When compared to age-matched WKY rats, the number of caudal artery receptors was higher in young and lower in adult SHR. The number of melatonin receptors was higher in the area postrema of adult SHR when compared to adult WKY rats, but in the suprachiasmatic nucleus, no such differences between the two strains were present. Alterations in receptor density were not accompanied by changes in binding affinity. Our results indicate that in the rat melatonin receptors show different developmental patterns according to location and that the receptors may be expressed differentially in genetic hypertension. RP VISWANATHAN, M (reprint author), NIMH,PHARMACOL SECT,CLIN SCI LAB,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892, USA. NR 26 TC 37 Z9 37 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD DEC PY 1992 VL 56 IS 6 BP 864 EP 870 DI 10.1159/000126318 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA KT210 UT WOS:A1992KT21000014 PM 1369596 ER PT J AU RAMIREZ, M SANCHEZ, B AECHAGA, G LARDELLI, P VENZON, D GARCIA, S OZAITA, A DEGANDARIAS, JM AF RAMIREZ, M SANCHEZ, B AECHAGA, G LARDELLI, P VENZON, D GARCIA, S OZAITA, A DEGANDARIAS, JM TI DAILY RHYTHM OF ASPARTATE AMINOPEPTIDASE ACTIVITY IN THE RETINA, PINEAL-GLAND AND OCCIPITAL CORTEX OF THE RAT SO NEUROENDOCRINOLOGY LA English DT Article DE DIURNAL VARIATION; ASPARTATE AMINOPEPTIDASE; RETINA; PINEAL; OCCIPITAL CORTEX; SERUM ID ANGIOTENSIN-CONVERTING ENZYME; BRAIN; RENIN; RECEPTORS; PITUITARY; TISSUES; SYSTEM AB The levels of specific soluble aspartyl aminopeptidase activity were assayed in retina, occipital cortex, anterior pituitary, posterior pituitary, pineal gland and serum of adult male rats, using Asp-2-naphthylamide as substrate, in a 12:12 h light:dark cycle (7-19 h light). Significant diurnal variations appeared in retina, pineal gland, occipital cortex and serum. In addition, different patterns of diurnal variation. of the enzymatic activity were observed in the tissues analyzed. A regular increase of the activity was noticed at the end of the dark period in all the tissues as a common feature, except in serum, in which the enzymatic activity reached a peak in the middle of the light period, decreasing progessively during the dark hours. After the last hours of darkness, the pattern of variation in the activity differed in each tissue. These diurnal variations in aspartyl aminopeptidase activity could reflect the functional status of its putative endogenous substrates, such as angiotensin II, and it may also suggest the existence of differential regulatory mechanisms associated with each location. C1 UNIV BASQUE COUNTRY,SCH MED,DEPT PHYSIOL,LEIOA,SPAIN. NIH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 14 TC 11 Z9 11 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD DEC PY 1992 VL 56 IS 6 BP 926 EP 929 DI 10.1159/000126326 PG 4 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA KT210 UT WOS:A1992KT21000023 PM 1369604 ER PT J AU FULHAM, MJ BROOKS, RA HALLETT, M DICHIRO, G AF FULHAM, MJ BROOKS, RA HALLETT, M DICHIRO, G TI CEREBELLAR DIASCHISIS REVISITED - PONTINE HYPOMETABOLISM AND DENTATE SPARING SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; 2 MAINTAINED POSTURES; BLOOD-FLOW; PROMPT MOVEMENTS; CELL OUTPUT; NEURONS; METABOLISM; INFARCTION; MONKEY AB A unilateral supratentorial lesion may cause hypometabolism in the contralateral cerebellar hemisphere (crossed cerebellar diaschisis). We analyzed glucose metabolism, measured by PET-FDG, in the posterior fossa in 67 patients (78 PET studies) with primary unilateral supratentorial brain tumors selected for visually obvious metabolic asymmetry in the cerebellar hemispheres. We found that glucose utilization was 17% lower in the contralateral cerebellar cortex (compared with the ipsilateral one), consistent with the selection criterion, and 19% lower in the ipsilateral pons, wherein lie the first order synapses of the corticopontocerebellar pathway. This finding helps to validate the prevalent view that cerebellar diaschisis is due to interruption of afferent input from the corticopontocerebellar pathway. However, glucose-metabolism in the contralateral dentate nucleus was relatively preserved-only 2% less than the ipsilateral dentate. This "dentate sparing" suggests preservation of afferent input to the largest of the deep cerebellar nuclei from the Purkinje cells in the cortex, despite interruption of the major excitatory input to the Purkinje cells. C1 NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NR 43 TC 46 Z9 46 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1992 VL 42 IS 12 BP 2267 EP 2273 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA KC375 UT WOS:A1992KC37500005 PM 1461377 ER PT J AU DAVIDSON, RA FEDIO, P SMITH, BD AUREILLE, E MARTIN, A AF DAVIDSON, RA FEDIO, P SMITH, BD AUREILLE, E MARTIN, A TI LATERALIZED MEDIATION OF AROUSAL AND HABITUATION - DIFFERENTIAL BILATERAL ELECTRODERMAL ACTIVITY IN UNILATERAL TEMPORAL LOBECTOMY PATIENTS SO NEUROPSYCHOLOGIA LA English DT Article ID LOBE EPILEPSY; SKIN-CONDUCTANCE; EXTRAVERSION; RECOGNITION; RESPONSES; ANXIETY AB The purpose of the present study was to increase our understanding of the differential hemispheric processing of arousal and habituation. Subjects were unilateral temporal lobectomy patients and controls. Each was exposed to an arousal/habituation task consisting of a series of tones and an auditory discrimination paradigm. Electrodermal activity was recorded from the left and right hands throughout. Results provide evidence for a state of hypoarousal in right temporal patients and some support for hyperarousability in lefts. This is consistent with data showing that right hemisphere damage is associated with inattention and denial and left hemisphere damage with hypervigilance and anxiety. The concept of laterally differentiated mediation of arousal and habituation was supported. C1 NINCDS,BLDG 10,ROOM 5D-49,BETHESDA,MD 20892. UNIV MARYLAND,COLL PK,MD 20742. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NIMH,BETHESDA,MD 20892. RI martin, alex/B-6176-2009 NR 45 TC 35 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD DEC PY 1992 VL 30 IS 12 BP 1053 EP 1063 DI 10.1016/0028-3932(92)90098-7 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA KE746 UT WOS:A1992KE74600003 PM 1484601 ER PT J AU KANT, AK BLOCK, G SCHATZKIN, A NESTLE, M AF KANT, AK BLOCK, G SCHATZKIN, A NESTLE, M TI ASSOCIATION OF FRUIT AND VEGETABLE INTAKE WITH DIETARY-FAT INTAKE SO NUTRITION RESEARCH LA English DT Article DE FRUITS AND VEGETABLES; DIETARY FAT; DIETARY GUIDANCE; NHANES-II; DIETARY PATTERNS; FOOD GROUPS AB We examined the relation of fruit and vegetable intake with dietary fat intake under conditions in which individuals consume recommended number of portions of dairy, meat and grain foods, using 24-hour dietary recall data from the NHANES II of 1976-80. only recalls that included at least 2 servings each of dairy foods and meat and 4 servings of grains, but variable servings of fruits and vegetables (ranging from 0 to 2 or more) were examined, yielding a total of 9 food group patterns (possible combinations of food group servings) as reported by 1,490 respondents. In patterns ranging from 0 to 2 servings each of fruits and vegetables, the mean percent of energy as fat varied from 39% to 36%. We observed a slight trend for decreasing energy from fat with increasing number of fruit-but not vegetable-servings. Consumption of fruits and vegetables was not associated with selection of lower-fat foods in the meat, dairy or grain groups. The percent of daily fat contributed by the miscellaneous food group (containing visible fats, sweeteners, and baked products with a high fat or sugar content) increased with increasing vegetable-but not fruit-servings. These results suggest that without conscious effort to reduce fat intake, an increase in fruit and vegetable intake may have a relatively minor impact on reduction of dietary fat. C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. NCI,BETHESDA,MD 20892. NYU,NEW YORK,NY 10003. RP KANT, AK (reprint author), CUNY QUEENS COLL,65-30 KISSENA BLVD,REMSEN HALL,ROOM 306,FLUSHING,NY 11367, USA. RI Block, Gladys/E-3304-2010 NR 17 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD DEC PY 1992 VL 12 IS 12 BP 1441 EP 1454 DI 10.1016/S0271-5317(05)80186-1 PG 14 WC Nutrition & Dietetics SC Nutrition & Dietetics GA KA776 UT WOS:A1992KA77600003 ER PT J AU LAKATTA, EG AF LAKATTA, EG TI INTERACTION BETWEEN NUTRITION AND AGING - A SUMMARY OF EFFECTS ON THE CARDIOVASCULAR-SYSTEM SO NUTRITION REVIEWS LA English DT Review ID MYOCYTES C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. RP LAKATTA, EG (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224, USA. NR 6 TC 1 Z9 1 U1 0 U2 1 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD DEC PY 1992 VL 50 IS 12 BP 419 EP 420 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA KF735 UT WOS:A1992KF73500020 PM 1488181 ER PT J AU BONARDI, R CECCHINI, S GRAZZINI, G CIATTO, S AF BONARDI, R CECCHINI, S GRAZZINI, G CIATTO, S TI LOOP ELECTROSURGICAL EXCISION PROCEDURE OF THE TRANSFORMATION ZONE AND COLPOSCOPICALLY DIRECTED PUNCH BIOPSY IN THE DIAGNOSIS OF CERVICAL LESIONS SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; CARCINOMA AB Objective: To estimate the disagreement between the histologic reports at colposcopically directed punch biopsy of the cervix and subsequent loop excision of the transformation zone, and to assess the indications for loop excision in current practice. Methods: The histologic diagnoses from loop electrosurgical excision procedures and concurrent colposcopically directed punch biopsies were compared in 337 consecutive women undergoing loop excision in a 5-year period. Results: Disagreement between punch biopsy and loop excision was recorded in 190 cases (56.4%). The undercall and overcall rates for punch biopsy were 14 and 42.4%, respectively. Undercall at punch biopsy occurred in 24 of 46 cases of cervical intraepithelial neoplasia (CIN) III and in one microinvasive cancer diagnosed at loop excision, and disagreement was within one grade of CIN in 16 cases. Conclusions: Loop electrosurgical excision allows further and more accurate histologic examination of the transformation zone and should be the standard assessment procedure in all cases of CIN II detected at punch biopsy and whenever cytology or colposcopy suggests the risk of punch biopsy undercall. Immediate treatment by local destruction should not be performed, to avoid underestimation of the severity of the lesion. C1 NATL CANC INST,GENOA,ITALY. RP BONARDI, R (reprint author), CTR STUDIO & PREVENZ ONCOL,VIALE A VOLTA 171,I-50131 FLORENCE,ITALY. RI Grazzini, Grazia/K-8503-2016 OI Grazzini, Grazia/0000-0002-9713-3007 NR 12 TC 40 Z9 44 U1 0 U2 1 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 DEC PY 1992 VL 80 IS 6 BP 1020 EP 1022 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA KA566 UT WOS:A1992KA56600026 PM 1448246 ER PT J AU LAMMIE, GA SMITH, R SILVER, J BROOKES, S DICKSON, C PETERS, G AF LAMMIE, GA SMITH, R SILVER, J BROOKES, S DICKSON, C PETERS, G TI PROVIRAL INSERTIONS NEAR CYCLIN D1 IN MOUSE LYMPHOMAS - A PARALLEL FOR BCL1 TRANSLOCATIONS IN HUMAN B-CELL NEOPLASMS SO ONCOGENE LA English DT Article ID MURINE LEUKEMIA-VIRUS; T(11-14) CHROMOSOME-TRANSLOCATION; MAMMARY-TUMOR VIRUS; C-MYC ONCOGENE; T-CELL; CANDIDATE ONCOGENE; MOLECULAR-CLONING; PUTATIVE ONCOGENE; VIRAL INTEGRATION; ACTIVATION AB By isolating genomic DNA clones that encompass the mouse Cyl-1 (cyclin D1) locus, we have identified a putative CpG island close to the 5' end of the gene. Pulsed-field gel electrophoresis with probes derived from either the 5' or 3' side of the CpG island established physical linkage to two independent markers on mouse chomosome 7, in a region that is syntenic with human chromosome 11q13. On the 3' side, Cyl-1 is approximately 75 kb from Hst-1 and Int-2, although there is an additional CpG island in the intervening DNA, while on the 5' side, Cyl-1 is less than 300 kb from Fis-1, an integration site for Friend murine leukaemia virus. As there is no intervening CpG island, proviral insertions at Fis-1 could influence the expression of Cyl-1 and we describe two virally induced tumours in which this appears to be the case. The data suggest that proviral insertions near Cyl-1 in mouse lymphomas are functionally equivalent to the BCL1 translocations that activate cyclin D1 expression in human B-cell malignancies. C1 IMPERIAL CANC RES FUND,MOLEC ONCOL LABS,44 LINCOLNS INN FIELDS,LONDON WC2A 3PX,ENGLAND. IMPERIAL CANC RES FUND,VIRAL CARCINOGENESIS LABS,LONDON WC2A 3PX,ENGLAND. NIH,BETHESDA,MD 20982. NR 41 TC 59 Z9 59 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1992 VL 7 IS 12 BP 2381 EP 2387 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA KA856 UT WOS:A1992KA85600002 PM 1461646 ER PT J AU THE, SM XIE, XL SMYTH, F PAPAS, TS WATSON, DK SCHULZ, RA AF THE, SM XIE, XL SMYTH, F PAPAS, TS WATSON, DK SCHULZ, RA TI MOLECULAR CHARACTERIZATION AND STRUCTURAL ORGANIZATION OF D-ELG, AN ETS PROTO-ONCOGENE-RELATED GENE OF DROSOPHILA SO ONCOGENE LA English DT Article ID PUTATIVE 2ND-CELL-DERIVED ONCOGENE; AVIAN LEUKEMIA RETROVIRUS-E26; LONG TERMINAL REPEAT; DNA-BINDING; C-ETS; C-ETS-1 PROTOONCOGENE; V-ETS; DEVELOPMENTAL EXPRESSION; TRANSCRIPTION FACTORS; TRANSFORMING GENE AB We have continued the molecular analysis of D-elg, a member of the Drosophila ets gene family. Based on the characterization of cDNA and genomic sequences, the D-elg gene contains five exons and four introns and produces a mRNA with an open reading frame of 464 amino acids. Consistent with this analysis, in vitro translation of a near full-length D-elg cRNA yields a protein with a molecular weight of approximately 56 kDa. D-elg shows significant homology to other ets proteins in the amino-terminal A domain and strong homology in the carboxy-terminal ETS domain. The D-elg protein is most similar to the alpha-subunit of the mouse GA-binding protein. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX 77030. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. NR 60 TC 12 Z9 13 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1992 VL 7 IS 12 BP 2471 EP 2478 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA KA856 UT WOS:A1992KA85600012 PM 1461651 ER PT J AU PAULES, RS RESNICK, J KASENALLY, AB ERNST, MK DONOVAN, P VANDEWOUDE, GF AF PAULES, RS RESNICK, J KASENALLY, AB ERNST, MK DONOVAN, P VANDEWOUDE, GF TI CHARACTERIZATION OF ACTIVATED AND NORMAL MOUSE MOS GENE IN MURINE 3T3 CELLS SO ONCOGENE LA English DT Article ID PROTO-ONCOGENE PRODUCT; MEIOTIC MATURATION; SARCOMA-VIRUS; M-PHASE; DEVELOPMENTAL REGULATION; OOCYTE MATURATION; XENOPUS OOCYTES; CDC2 PROTEIN; GERM-CELLS; MEIOSIS-II AB We have characterized the mouse Mos proto-oncogene product, pp39Mos in murine fibroblasts. When expressed in NIH3T3 cells under the influence of the long terminal repeat regulatory element from Moloney murine sarcoma virus [NIH(pTS-1) cells], the Mos protein was present in low levels and had a half-life of about 30 min. In extracts from NIH(pTS-1) cells, we detected additional forms of Mos protein that apparently arose from internal initiation codons (p24Mos and p29Mos) or from upstream non-AUG initiation codons (p42Mos and p44Mos). The Mos protein was found to exist in these cells as a phosphoprotein, pp39Mos, and, when immunoprecipitated with an antiserum specific for the Mos N-terminus [anti-Mos(6-24)], had autophosphorylating kinase activity. We found that anti-Mos(6-24) also detected non-Mos protein kinase activity and non-Mos phosphoproteins in addition to p39Mos. We present evidence, on both the RNA and protein levels, that non-transformed mouse 3T3 cells do not express endogenous Mos. C1 ST MARYS HOSP,SCH MED,LUDWIG INST CANC RES,LONDON W2 1PG,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ABL,FREDERICK,MD 21702. RP PAULES, RS (reprint author), NIEHS,MAMMALIAN MOLEC GENET GRP,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [N01-CO-74101] NR 51 TC 18 Z9 18 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1992 VL 7 IS 12 BP 2489 EP 2498 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA KA856 UT WOS:A1992KA85600014 PM 1461652 ER PT J AU SALIVE, ME GURALNIK, J CHRISTEN, W GLYNN, RJ COLSHER, P OSTFELD, AM AF SALIVE, ME GURALNIK, J CHRISTEN, W GLYNN, RJ COLSHER, P OSTFELD, AM TI FUNCTIONAL BLINDNESS AND VISUAL IMPAIRMENT IN OLDER ADULTS FROM 3 COMMUNITIES SO OPHTHALMOLOGY LA English DT Article ID EYE AB Purpose: The purpose of this study is to examine the association of sociodemographic factors with functional blindness and visual impairment in an aged population. Methods: Three population-based cohorts (East Boston, MA; New Haven, CT; and Iowa and Washington Counties, IA) of persons aged 71 years and older were screened for bilateral functional near and distant vision during an in-home interview in 1988. Results: Screening was completed by 5335 participants. The prevalence of functional blindness increased with age, from 1% at age 71 to 74 years to 17% in those 90 years of age and older. Functional visual impairment increased from 7% at age 71 to 74 years to 39% in those 90 years of age and older. In multivariate analyses, residence in a nursing home, older age, glaucoma, insulin-requiring diabetes at baseline, East Boston site, history of cataract, and lower 1982 income were independent and significantly associated with both functional blindness and visual impairment. Age and nursing home residence were significantly (P < 0.05) more strongly associated with blindness (odds ratios 4.8 and 6.1, respectively) than they were with visual impairment. Conclusion: Functional blindness and visual impairment are quite prevalent among the oldest old and the institutionalized. The number of affected individuals will increase as the population ages and life expectancy increases. Although visual problems are associated with aging, nursing home residence, health problems, and socioeconomic conditions, they may be readily remediable and may lead to immediate improvements in quality of life. C1 HARVARD UNIV,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA 02115. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. YALE UNIV,SCH MED,DEPT EPIDEMIOL,NEW HAVEN,CT 06510. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,SUITE 3C309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-02105, N01-AG-02106, N01-AG-02107] NR 17 TC 101 Z9 103 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1992 VL 99 IS 12 BP 1840 EP 1847 PG 8 WC Ophthalmology SC Ophthalmology GA KE755 UT WOS:A1992KE75500025 PM 1480401 ER PT J AU SAAVEDRA, JE FARNSWORTH, DW AF SAAVEDRA, JE FARNSWORTH, DW TI SELECTIVE NITROSATION OF DIALKYLUREAS CONTAINING A BASIC BETA-NITROGEN SO ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL LA English DT Article ID KINETICS C1 NCI,FCRDC,BASIC RES PROGRAM,ABL,FREDERICK,MD 21702. RP SAAVEDRA, JE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU ORGANIC PREP PROCEDURES INC PI NEWTON HIGHLANDS PA PO BOX 9, NEWTON HIGHLANDS, MA 02161 SN 0030-4948 J9 ORG PREP PROCED INT JI Org. Prep. Proced. Int. PD DEC PY 1992 VL 24 IS 6 BP 655 EP 659 PG 5 WC Chemistry, Organic SC Chemistry GA KB493 UT WOS:A1992KB49300003 ER PT J AU MUELLER, BU PIZZO, PA AF MUELLER, BU PIZZO, PA TI TRIMETHOPRIM-SULFAMETHOXAZOLE PROPHYLAXIS OF PNEUMOCYSTIS-CARINII PNEUMONIA IN INFANTS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Letter DE PEDIATRIC HUMAN IMMUNODEFICIENCY VIRUS INFECTION; PNEUMOCYSTIS-CARINII; TRIMETHOPRIM-SULFAMETHOXAZOLE ID CHEMOPROPHYLAXIS RP MUELLER, BU (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 1992 VL 11 IS 12 BP 1072 EP 1073 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA KB533 UT WOS:A1992KB53300026 PM 1461709 ER PT J AU SOMEKH, E TEDDER, DG VAFAI, A ASSOULINE, JG STRAUS, SE WILCOX, CL LEVIN, MJ AF SOMEKH, E TEDDER, DG VAFAI, A ASSOULINE, JG STRAUS, SE WILCOX, CL LEVIN, MJ TI LATENCY INVITRO OF VARICELLA-ZOSTER VIRUS IN CELLS DERIVED FROM HUMAN FETAL DORSAL-ROOT GANGLIA SO PEDIATRIC RESEARCH LA English DT Article ID HERPES-SIMPLEX VIRUS; HUMAN TRIGEMINAL GANGLIA; SCHWANN-CELLS; MONOCLONAL-ANTIBODIES; NERVE; EXPRESSION; NEURONS; PROTEIN; INFECTIONS; CHILDREN AB A potential in vitro model of varicella-zoster virus (VZV) latency was developed. Dissociated human dorsal root ganglion cultures were infected with VZV and maintained for 1 wk in the presence of bromovinyl arabinosyl uracil, a potent inhibitor of VZV. Seven to 21 d after removing the inhibitor (greater-than-or-equal-to 14 d after infection), the cells were trypsinized, passed to monolayers of human embryonic lung fibroblasts, and observed for VZV reactivation as indicated by typical cytopathic effects and the appearance of VZV antigens. VZV reactivated from 56% of the cultures containing both neurons and satellite cells but not from cultures specifically enriched for either neurons, satellite cells, or ganglion-derived fibroblasts. The failure to isolate VZV from cell suspensions that were sonicated before cocultivation with fibroblasts indicated that infectious VZV was not present before reactivation. Moreover, immunohistochemical and immunoprecipitation studies revealed no VZV-specific antigens in any cultures before the reactivation stimulus. VZV antigens were detected after trypsinization and cocultivation. These findings suggest that cultures containing both neurons and satellite cells provide a model system for VZV persistence that possesses many properties of a latent infection. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PEDIAT,INFECT DIS SECT,CAMPUS BOX C-227,4200 E 9TH AVE,DENVER,CO 80262. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,MOLEC VIROL & GENET SECT,BETHESDA,MD 20892. UNIV ILLINOIS,COLL MED,DEPT BIOMED SCI,ROCKFORD,IL 61107. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. UNIV COLORADO,SCH MED,DEPT MICROBIOL,DENVER,CO 80262. FU NIA NIH HHS [P01AG07347-04]; NIAID NIH HHS [AI-20381] NR 31 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD DEC PY 1992 VL 32 IS 6 BP 699 EP 703 DI 10.1203/00006450-199212000-00016 PG 5 WC Pediatrics SC Pediatrics GA JZ792 UT WOS:A1992JZ79200013 PM 1337586 ER PT J AU FOWLER, MG DAVENPORT, MG GARG, R AF FOWLER, MG DAVENPORT, MG GARG, R TI SCHOOL FUNCTIONING OF UNITED-STATES CHILDREN WITH ASTHMA SO PEDIATRICS LA English DT Article DE ASTHMA; SCHOOL FUNCTIONING; ABSENCES ID CHILDHOOD ASTHMA; PSYCHOLOGICAL ADJUSTMENT; CHANGING PATTERNS; PREVALENCE; MORTALITY; ILLNESS; RATES AB Data from the 1988 US National Health Interview Survey on Child Health, a nationally representative cross-sectional survey, were used to determine national estimates of school outcomes (grade failure, learning disabilities, and suspension/expulsion) and mean number of absences for children with asthma (CWA) compared to well children without current health conditions. Families indicated that 536 (4.9%) of the 10 362 survey children in grades 1 through 12 had had asthma in the previous 12 months. Families reported 18% of CWA vs 15% of well children had grade failure, 9% of CWA vs 5% of well children had learning disabilities, and 5% of CWA vs 6% of well children had been expelled or suspended. Children with asthma averaged 7.6 school days absent compared with 2.5 days for the well group. Multiple logistic regression was used to compare the odds of grade failure, learning disabilities, and suspension/expulsion among CWA and well children, overall and stratified by income. Similar methods were used to assess the role of health status among asthmatic children. After adjustment for demographic factors, CWA had similar risks of grade failure and suspension/expulsion, but 1.7 times the risk of learning disability compared with well children. Also, among families with incomes below $20 000, CWA had twice the odds of grade failure compared with well children. For asthmatic children, reported health status was an important predictor of learning disability. Ten percent of CWA were reported to be in fair-poor health. After adjustment for demographic factors, those in fair-poor health were twice as likely to have a reported learning disability compared with those in good-excellent health. These national data suggest a modestly increased risk of academic problems among children with asthma compared with well children. C1 NATL CTR HLTH STAT, HYATTSVILLE, MD 20782 USA. NHLBI, BETHESDA, MD 20892 USA. NR 29 TC 150 Z9 155 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD DEC PY 1992 VL 90 IS 6 BP 939 EP 944 PG 6 WC Pediatrics SC Pediatrics GA KF504 UT WOS:A1992KF50400020 PM 1437438 ER PT J AU ROTHMAN, RB GRIEG, N KIM, A DECOSTA, BR RICE, KC CARROLL, FI PERT, A AF ROTHMAN, RB GRIEG, N KIM, A DECOSTA, BR RICE, KC CARROLL, FI PERT, A TI COCAINE AND GBR12909-PRODUCE EQUIVALENT MOTORIC RESPONSES AT DIFFERENT OCCUPANCY OF THE DOPAMINE TRANSPORTER SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE GBR12909; NOMIFENSINE; COCAINE; DOPAMINE; LOCOMOTOR ACTIVITY ID INDUCED LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; UPTAKE COMPLEX; SIGMA-LIGANDS; RAT STRIATUM; GBR 12909; BINDING; INVIVO; AMPHETAMINE; INHIBITORS AB The motoric-stimulating effect of dopamine (DA) reuptake blockers is thought to result from the increase in synaptic dopamine levels, which occurs as a consequence of blockade of DA reuptake. The present study tested measured occupancy of the DA transporter in vivo produced by behaviorally equivalent doses of the DA reuptake blockers GBR12909 (20 mg/kg), cocaine (20 mg/kg),WIN35-065-2 (I mg/kg), and nomifensine (5 mg/kg). Two methods were used to measure in vivo occupancy of the DA transporter: a) an ex vivo method, in which the ability of whole brain supernatants, prepared from rats administered the test drugs, were tested for their ability to inhibit the reuptake of [H-3]DA by striatal synaptosomes; and b) an in vivo binding assay using [3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine ([H-3]BTCP) to label the striatal DA transporter in vivo. Considerable data support the notion that this measurement is predictive of transporter occupancy in the nucleus accumbens. Similar results were obtained with both methods: The order of potency for apparent transporter occupancy was GBR12909 >> nomifensine > WIN35-065-2 = cocaine. These data indicate that it takes greater occupancy of the DA transporter by GBR12909 to produce behavioral effects equivalent to those produced by cocaine at lower transporter occupancy. The data of the present study suggest, therefore, that studies relating the effects of DA reuptake inhibitors on DA-mediated motoric behaviors to DA transporter occupancy might facilitate the identification of novel compounds potentially useful for the pharmacotherapy of cocaine abuse. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP ROTHMAN, RB (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 30 TC 76 Z9 77 U1 1 U2 1 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 DEC PY 1992 VL 43 IS 4 BP 1135 EP 1142 DI 10.1016/0091-3057(92)90493-Y PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JZ943 UT WOS:A1992JZ94300024 PM 1475296 ER PT J AU LIPSKA, BK JASKIW, GE ARYA, A WEINBERGER, DR AF LIPSKA, BK JASKIW, GE ARYA, A WEINBERGER, DR TI SEROTONIN DEPLETION CAUSES LONG-TERM REDUCTION OF EXPLORATION IN THE RAT SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE SEROTONIN; 5,7-DIHYDROXYTRYPTAMINE; AMPHETAMINE; FG-7142; EXPLORATION; LOCOMOTOR ACTIVITY ID CENTRAL NERVOUS-SYSTEM; LOCOMOTOR-ACTIVITY; PARA-CHLOROPHENYLALANINE; NUCLEUS ACCUMBENS; BRAIN DOPAMINE; FORNIX-FIMBRIA; 5,7-DIHYDROXYTRYPTAMINE; AMPHETAMINE; LESIONS; 5-HYDROXYTRYPTAMINE AB This study assessed the effects of central serotonergic depletion on exploratory activity at baseline, as well as after administration of d-amphetamine or the anxiogenic beta-carboline FG-7142. Intraventricular 5,7-dihydroxytryptamine (5,7-DHT) induced an almost complete depletion of serotonin 15-hydroxytryptamine (5-HT)] in the medial prefrontal cortex, nucleus accumbens, medial corpus striatum, and hippocampus with no changes in norepinephrine, dopamine or dihydroxyphenylacetic acid concentrations. 5-HT-depleted rats demonstrated reduced spontaneous and d-amphetamine-augmented exploration 3-10 weeks postoperatively. An effect on FG-7142-induced inhibition of exploratory activity was not apparent. These data implicate 5-HT systems in the expression of different aspects of exploratory and amphetamine-augmented motor behaviors. C1 NIH,CLIN PHARMACOL SECT,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP LIPSKA, BK (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 46 TC 44 Z9 44 U1 0 U2 1 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 DEC PY 1992 VL 43 IS 4 BP 1247 EP 1252 DI 10.1016/0091-3057(92)90510-M PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JZ943 UT WOS:A1992JZ94300041 PM 1475309 ER PT J AU WALDEN, TL FARZANEH, NK HEARING, VJ GERSTEN, DM AF WALDEN, TL FARZANEH, NK HEARING, VJ GERSTEN, DM TI PROTEINURIA OF B700, A 67 KD ALBUMIN-LIKE MELANOMA-SPECIFIC ANTIGEN SO PIGMENT CELL RESEARCH LA English DT Article DE B700; ALBUMIN; PROTEINURIA; MELANOMA ANTIGEN ID D BINDING-PROTEIN; SERUM-ALBUMIN; URINE; GLYCOPROTEIN; INVIVO; FATE AB B700 is a murine melanoma antigen that is closely related to, but distinct from, serum albumin. The present study examined the metabolic fate and anatomic distribution of radioiodinated B700 and mouse serum albumin (MSA) administered s.c. to mice. In blood, both proteins were associated with the plasma fraction where the halflife of B700, a glycoprotein, was 0.5 days, compared to 2.7 days for MSA. Of particular interest was the observation that B700, a 67 kD anionic protein, was excreted primarily in urine. The selective B700-proteinuria did not alter urinary volumes or produce hematuria or edema. SDS-polyacrylamide gel electrophoresis and western blot analysis using the H-2-3-3 B700-specific monoclonal antibody revealed that B700 proteinuria occurred in B-16 murine melanoma bearing animals but not in control mice. These studies demonstrate that the tumor-bearing host readily distinguishes between very similar normal protein (MSA) and tumor-associated antigen (B700) molecules and processes them differently. C1 GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20007. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 28 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD DEC PY 1992 VL 5 IS 6 BP 387 EP 393 DI 10.1111/j.1600-0749.1992.tb00567.x PG 7 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA KL034 UT WOS:A1992KL03400004 PM 1492072 ER PT J AU DAVIS, ES BECKER, A HEITMAN, J HALL, MN BRENNAN, MB AF DAVIS, ES BECKER, A HEITMAN, J HALL, MN BRENNAN, MB TI A YEAST CYCLOPHILIN GENE ESSENTIAL FOR LACTATE METABOLISM AT HIGH-TEMPERATURE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MITOCHONDRIA; TEMPERATURE SENSITIVE ID CIS-TRANS-ISOMERASE; A-BINDING PROTEIN; CYCLOSPORIN-A; SACCHAROMYCES-CEREVISIAE; NEUROSPORA-CRASSA; ESCHERICHIA-COLI; MITOCHONDRIA; HOMOLOG; DNA; EXPRESSION AB The cyclophilins are a family of ubiquitous eukaryotic proteins first identified by high affinity for cyclosporin A (CsA). The immunosuppressant and cytotoxic effects of CsA are thought to result from formation of a toxic complex between cyclophilin and CsA rather than from inhibition of cyclophilin function. The physiological role(s) of the cyclophilins is unknown. Cyclophilins have in vitro peptidylprolyl cis-trans isomerase (PPIase) activity, and thus may be involved in protein folding in vivo. We have isolated a yeast cyclophilin gene, CPR3, which encodes a presumptive mitochondrial isoform. While CPR3 disruption mutants lack any phenotype at 30-degrees-C, they are unable to grow on L-lactate at 37-degrees-C. Disruptions of two other cyclophilin genes (CPR1, CPR2) and of FPR1, the gene encoding an FK506 binding protein with PPIase activity, do not affect growth on L-lactate at 37-degrees-C. L-Lactate metabolism requires transcriptional induction of CYB2, the gene encoding flavocytochrome b2; cpr3 mutants induce transcription of this gene normally. This result demonstrates a conditional lethal phenotype for a cyclophilin mutation and presents a system for genetic and biochemical analysis of cyclophilin function. C1 NIMH, CLIN NEUROGENET BRANCH,GENOM UNIT,BLDG 10, ROOM 4N320, BETHESDA, MD 20892 USA. UNIV BASEL, BIOCTR, DEPT BIOCHEM, CH-4056 BASEL, SWITZERLAND. Scripps Res Inst, RES INST, DEPT MOLEC BIOL, LA JOLLA, CA 92037 USA. UNIV MARYLAND, DEPT ZOOL, COLL PK, MD 20742 USA. NR 34 TC 72 Z9 74 U1 0 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1992 VL 89 IS 23 BP 11169 EP 11173 DI 10.1073/pnas.89.23.11169 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA903 UT WOS:A1992KA90300015 PM 1454795 ER PT J AU LISZIEWICZ, J SUN, D KLOTMAN, M AGRAWAL, S ZAMECNIK, P GALLO, R AF LISZIEWICZ, J SUN, D KLOTMAN, M AGRAWAL, S ZAMECNIK, P GALLO, R TI SPECIFIC-INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION BY ANTISENSE OLIGONUCLEOTIDES - AN INVITRO MODEL FOR TREATMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ESCAPE MUTANTS; THERAPEUTIC AVOIDANCE ID CHRONICALLY INFECTED-CELLS; GENE-EXPRESSION REQUIRES; PHOSPHOROTHIOATE ANALOGS; TRANS-ACTIVATOR; VIRAL-RNA; HTLV-III; OLIGODEOXYNUCLEOTIDES; SEQUENCE; BINDING; LATENCY AB We have developed a culture system, simulating in vivo conditions of human immunodeficiency virus type 1 (HIV-1) infection, to evaluate the long-term efficacy of antisense oligonucleotide treatment. Five oligonucleotide phosphorothioates (28-mers), complementary to different regions of HIV-1 RNA, blocked replication of the virus in a sequence-specific manner at 1 muM concentration. Variations in antiviral activity were seen among the different oligonucleotides, revealing an effect of target selection. Mismatched or random oligonucleotide phosphorothioates delayed, but did not completely inhibit, HIV-1 replication. In the case of inhibition by a splice-acceptor-site antisense oligodeoxynucleotide, a breakthrough phenomenon occurred after 25 days of treatment, suggesting the development of an "escape mutant." This result did not occur when the inhibitory oligodeoxynucleotides were complementary to the primary-sequence areas of the rev-responsive element and rev-1 genes. Sequential treatment of HIV-1-infected cells with a combination of different antisense oligonucleotides, each administered once, also prevented the development of escape mutants. Our results suggest that chemotherapy based on specifically targeted antisense-oligonucleotide phosphorothioates may be an effective method for reducing the viral burden in HIV-1-infected individuals at clinically achievable oligonucleotide concentrations. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. WORCESTER FDN EXPTL BIOL INC,SHREWSBURY,MA 01545. RI klotman, mary/A-1921-2016 FU PHS HHS [P30-12708-17, A1-24846] NR 25 TC 109 Z9 110 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1992 VL 89 IS 23 BP 11209 EP 11213 DI 10.1073/pnas.89.23.11209 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA903 UT WOS:A1992KA90300023 PM 1454800 ER PT J AU CHOY, HE ADHYA, S AF CHOY, HE ADHYA, S TI CONTROL OF GAL TRANSCRIPTION THROUGH DNA LOOPING - INHIBITION OF THE INITIAL TRANSCRIBING COMPLEX SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLI GALACTOSE OPERON; ESCHERICHIA-COLI; LAC-REPRESSOR; CYCLIC-AMP; RNA-POLYMERASE; PROTEIN; OPERATOR; GENE; BINDING; PROMOTERS AB Involvement of DNA looping between two spatially separated gal operators, O(E) and O(I), in repression of the gal operon has been demonstrated in vivo. An in vitro transcription assay using a minicircle DNA containing the gal promoter region with lac operators was employed to elucidate the molecular mechanism of repression. Wild-type lac repressors (LacI+ protein molecules), which are capable of associating into a tetramer and forming a DNA loop, repressed transcription from promoter sites P1 and P2, whereas a non-looping lac repressor mutant (LacI(adi)) failed to show normal repression of both of the gal promoters. Thus a DNA loop is also required for repression of transcription in vitro. Repression mediated by DNA looping resulted in the inhibition of the synthesis of complete as well as aborted transcripts, demonstrating that the repressive action was on the formation or activity of the initial transcribing complex. Under similar conditions, the gal repressor (GalR protein) did not repress the gal promoters effectively, apparently because it failed to loop DNA containing gal operators in the purified system. The component(s) or conditions that aid GalR in DNA looping remain to be identified. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 28 TC 83 Z9 83 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1992 VL 89 IS 23 BP 11264 EP 11268 DI 10.1073/pnas.89.23.11264 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA903 UT WOS:A1992KA90300034 PM 1454806 ER PT J AU ZOLKIEWSKA, A NIGHTINGALE, MS MOSS, J AF ZOLKIEWSKA, A NIGHTINGALE, MS MOSS, J TI MOLECULAR CHARACTERIZATION OF NAD-ARGININE ADP-RIBOSYLTRANSFERASE FROM RABBIT SKELETAL-MUSCLE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHOLERA TOXIN; GLYCOSYL-PHOSPHATIDYLINOSITOL ANCHOR; ADP-RIBOSYLARGININE HYDROLASE ID PSEUDOMONAS-AERUGINOSA; NUCLEOTIDE-SEQUENCE; TURKEY ERYTHROCYTES; ESCHERICHIA-COLI; DIPHTHERIA-TOXIN; EXOTOXIN-A; RIBOSYLATION; PROTEIN; GENE; ACID AB Mono-ADP-ribosylation is a reversible modification of proteins, with NAD:arginine ADP-ribosyltransferases (EC 2.4.2.31) and ADP-ribosylarginine hydrolases (EC 3.2.2.19) catalyzing the opposing reactions in an ADP-ribosylation cycle. A membrane-associated arginine-specific (mono)-ADP-ribosyltransferase was purified 215,000-fold from rabbit skeletal muscle. On the basis of the amino acid sequences of HPLC-purified tryptic peptides, degenerate oligonucleotide primers were synthesized and used in a polymerase chain reaction (PCR)-based procedure to generate cDNA. A specific probe, based on PCR-generated sequence, was used to screen a rabbit skeletal muscle cDNA library. A composite cDNA sequence, obtained from library screening and rapid amplification of the 5' end of the cDNA, contained a 981-base-pair open reading frame, encoding a 36,134-Da protein. The deduced amino acid sequence contained the sequences of the tryptic peptides, hydrophobic amino and carboxyl termini, and two potential sites for N-linked glycosylation. Escherichia coli cells transformed with an expression vector containing transferase-specific sequence expressed ADP-ribosyltransferase activity. A transferase-specific oligonucleotide probe recognized a 4-kilobase mRNA expressed primarily in rabbit skeletal and cardiac muscle. There was no extended similarity in deduced amino acid sequences of the muscle transferase and several bacterial ADP-ribosylating toxins. The hydrophobic amino and carboxyl termini may represent a signal peptide and a site for a glycosyl-phosphatidylinositol anchor, respectively. RP NHLBI, CELLULAR METAB LAB, BETHESDA, MD 20892 USA. NR 40 TC 162 Z9 163 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1992 VL 89 IS 23 BP 11352 EP 11356 DI 10.1073/pnas.89.23.11352 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA903 UT WOS:A1992KA90300052 PM 1454819 ER PT J AU KRAFT, T YU, LC KUHN, HJ BRENNER, B AF KRAFT, T YU, LC KUHN, HJ BRENNER, B TI EFFECT OF CA2+ ON WEAK CROSS-BRIDGE INTERACTION WITH ACTIN IN THE PRESENCE OF ADENOSINE 5'-[GAMMA-THIO]TRIPHOSPHATE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE WEAK-BINDING CROSS-BRIDGE STATES; STRONG-BINDING CROSS-BRIDGE STATES; ACTIN BINDING KINETICS; NUCLEOTIDE SATURATION; NUCLEOTIDE AFFINITY ID RABBIT PSOAS FIBERS; X-RAY-DIFFRACTION; FROG-MUSCLE FIBERS; SKELETAL-MUSCLE; MYOSIN SUBFRAGMENT-1; TROPONIN-TROPOMYOSIN; TENSION TRANSIENTS; ACTOMYOSIN ATPASE; FORCE GENERATION; RELAXED MUSCLE AB In the presence of the nucleotide analog adenosine 5'-[gamma-thio]triphosphate (ATP[gammaS]), effects of Ca2+ on stiffness and equatorial x-ray diffraction patterns of single skinned fibers of the rabbit psoas muscle were studied. It is shown that cross-bridges in the presence of ATP[gammaS] have properties of the weak-binding states of the ATP hydrolysis cycle. Raising the Ca2+ concentration up to pCa 4.5 has little effect on actin affinity of cross-bridges in the presence of ATP[gammaS]. However, the rate constants for cross-bridge dissociation and reassociation from and to actin are reduced by about 2 orders of magnitude. In addition, nucleotide affinity of the cross-bridge is much smaller at high Ca2+ concentrations. Implications for interpretation of fiber stiffness recorded during isotonic shortening and the rising phase of a tetanus are discussed. C1 NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892. RP KRAFT, T (reprint author), UNIV ULM,DEPT GEN PHYSIOL,ALBERT EINSTEIN ALLEE 11,W-7900 ULM,GERMANY. NR 46 TC 42 Z9 43 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1992 VL 89 IS 23 BP 11362 EP 11366 DI 10.1073/pnas.89.23.11362 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA903 UT WOS:A1992KA90300054 PM 1454820 ER PT J AU PRIBLUDA, VS METZGER, H AF PRIBLUDA, VS METZGER, H TI TRANSMEMBRANE SIGNALING BY THE HIGH-AFFINITY IGE RECEPTOR ON MEMBRANE PREPARATIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TYROSINE PHOSPHORYLATION; FC-EPSILON-RI; MAST CELLS ID BASOPHILIC LEUKEMIA-CELLS; IMMUNOGLOBULIN-E; TYROSINE PHOSPHORYLATION; MEDIATED HYDROLYSIS; CROSS-LINKING; PHOSPHOINOSITIDES; TRANSDUCTION; KINASES AB Aggregating the receptor with high affinity for IgE (FcepsilonRI) stimulates a variety of phenomena in mast cells. Previous efforts to reproduce some of these events in broken-cell preparations such as isolated membranes have had limited success, possibly because the phenomena being monitored were too distal from the initial events. One of the earliest responses is now known to be the phosphorylation of tyrosine residues on several proteins, including the beta and gamma subunits of FcepsilonRI. We show that in cell sonicates or on partially purified membranes derived from tumor mast cells, aggregating FcepsilonRI stimulates phosphorylation of receptor tyrosine residues. As in the intact cells, receptor-mediated phosphorylation occurs only on receptors that are themselves aggregated. Because even in the unfractionated sonicates the phosphorylation of other cellular components was not detectably enhanced, and because the evidence is against the receptor itself being a kinase, our results suggest that phosphorylation of FcepsilonRI is one of the earliest events stimulated by the receptor-an event that can now be investigated on simpler biological preparations than previously available. RP PRIBLUDA, VS (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,CHEM IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 25 TC 34 Z9 34 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1992 VL 89 IS 23 BP 11446 EP 11450 DI 10.1073/pnas.89.23.11446 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA903 UT WOS:A1992KA90300072 PM 1280826 ER PT J AU CHRISTIANSON, AMK KING, DL HATZIVASSILIOU, E CASAS, JE HALLENBECK, PL NIKODEM, VM MITSIALIS, SA KAFATOS, FC AF CHRISTIANSON, AMK KING, DL HATZIVASSILIOU, E CASAS, JE HALLENBECK, PL NIKODEM, VM MITSIALIS, SA KAFATOS, FC TI DNA-BINDING AND HETEROMERIZATION OF THE DROSOPHILA TRANSCRIPTION FACTOR CHORION FACTOR-1/ULTRASPIRACLE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STEROID-RECEPTOR SUPERFAMILY; HORMONE RECEPTOR; THYROID-HORMONE; SITE SELECTION; PROTEIN; MEMBER; ELEMENTS; GENE AB The Drosophila chorion factor 1/ultraspiracle (CF1/USP) transcription factor, a homologue of the retinoid X receptor, is a developmentally important member of the family of nuclear (steroid) hormone receptors. Using newly developed monoclonal antibodies and a full-length bacterially produced protein, we have studied in detail the in vitro DNA-binding properties of this factor and aspects of its distribution in vivo. During oogenesis, CF1/USP is present both in germ-line cells and in the somatic follicular epithelium. We have determined the optimal binding site of partially purified bacterially produced CF1/USP by an in vitro selection procedure and also have characterized its binding to the follicular-specific chorion s15 promoter. In vitro this bacterially produced factor is unusual in binding to a single element ("half-site"); simultaneous but noncoordinate binding to a second half-site is possible if these repeated elements are organized in direct orientation and spaced adequately. However, the factor interacts synergistically with several other nuclear hormone receptors: notably, it can form in vitro heteromers with mammalian thyroid and retinoic acid receptors, binding to two half-sites that are organized in either direct or inverted orientation. In vivo the factor most probably functions as a heterodimer, but its partner(s) remains to be determined. C1 HARVARD UNIV,DEPT CELLULAR & DEV BIOL,CAMBRIDGE,MA 02138. INST MOLEC BIOL & BIOTECHNOL,GR-71110 IRAKLION,GREECE. BOSTON UNIV HOSP,EVANS DEPT CLIN RES,BOSTON,MA 02218. BOSTON UNIV,SCH MED,DEPT MED,BOSTON,MA 02118. NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 33 TC 89 Z9 89 U1 0 U2 3 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1992 VL 89 IS 23 BP 11503 EP 11507 DI 10.1073/pnas.89.23.11503 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA903 UT WOS:A1992KA90300084 PM 1280827 ER PT J AU TRUS, BL NEWCOMB, WW BOOY, FP BROWN, JC STEVEN, AC AF TRUS, BL NEWCOMB, WW BOOY, FP BROWN, JC STEVEN, AC TI DISTINCT MONOCLONAL-ANTIBODIES SEPARATELY LABEL THE HEXONS OR THE PENTONS OF HERPES-SIMPLEX VIRUS CAPSID SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ELECTRON-MICROGRAPHS; CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL STRUCTURE; EQUINE HERPESVIRUS-1; SIMIAN VIRUS-40; PROTEINS; RECONSTRUCTION; POLYPEPTIDES; LOCALIZATION; SYMMETRY AB The surface shell of the capsid of herpes simplex virus type 1 (HSV-1) is 15 nm thick and 125 nm in outer diameter and has the form of an icosahedral (T = 16) surface lattice, composed of 150 hexons and 12 pentons. Hexons are traversed by axial channels and have six-fold symmetric external protrusions, separated by triangular nodules ("triplexes"). Pentons resemble hexons morphologically, apart from their different order of symmetry. To localize VP5, the major capsid protein, in the shell structure and to investigate whether pentons are composed of the same molecules as hexons, we have performed cryo-electron microscopy and three-dimensional image reconstructions of control HSV-1 B capsids and of B capsids immunoprecipitated with two monoclonal antibodies raised against purified VP5 and purified capsids. The results clearly map the epitope of the anti-VP5 monoclonal antibody to the distal tips of the hexon protrusions. In contrast, no detectable labeling of pentons was observed. We conclude that the hexon protrusions are domains of VP5 hexamers, other parts of these molecules forming the basic matrix of the capsid shell to which the other proteins are attached at specific sites. Conversely, the anti-capsid monoclonal antibody decorates the outer rim of pentons but does not bind to hexons. These observations imply that either pentons are composed of some other protein(s) or that they also contain VP5, but in a conformation sufficiently different from that assumed in hexons as to transform its antigenic character. Other evidence leads us to favor the latter alternative. C1 NIAMSD,STRUCT BIOL RES LAB,BLDG 6,ROOM 114,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,CTR CANC,CHARLOTTESVILLE,VA 22908. FU NIGMS NIH HHS [GM34036] NR 34 TC 96 Z9 96 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1992 VL 89 IS 23 BP 11508 EP 11512 DI 10.1073/pnas.89.23.11508 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA903 UT WOS:A1992KA90300085 PM 1280828 ER PT J AU SWEDO, SE LEONARD, HL RAPOPORT, JL AF SWEDO, SE LEONARD, HL RAPOPORT, JL TI CHILDHOOD-ONSET OBSESSIVE-COMPULSIVE DISORDER SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PROSPECTIVE FOLLOW-UP; CLOMIPRAMINE TREATMENT; ADOLESCENTS; CHILDREN; PHENOMENOLOGY; DESIPRAMINE; SCALE C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 39 TC 33 Z9 33 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1992 VL 15 IS 4 BP 767 EP 775 PG 9 WC Psychiatry SC Psychiatry GA KZ892 UT WOS:A1992KZ89200004 PM 1461794 ER PT J AU SWEDO, SE LEONARD, HL AF SWEDO, SE LEONARD, HL TI TRICHOTILLOMANIA - AN OBSESSIVE-COMPULSIVE SPECTRUM DISORDER SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID DOUBLE-BLIND CROSSOVER; FOLLOW-UP; CLOMIPRAMINE TREATMENT; HAIR LOSS; CHILDREN; ADOLESCENTS; FLUOXETINE; CHOREA; DESIPRAMINE; PREVALENCE C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 53 TC 116 Z9 118 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1992 VL 15 IS 4 BP 777 EP 790 PG 14 WC Psychiatry SC Psychiatry GA KZ892 UT WOS:A1992KZ89200005 PM 1461795 ER PT J AU INSEL, TR WINSLOW, JT AF INSEL, TR WINSLOW, JT TI NEUROBIOLOGY OF OBSESSIVE-COMPULSIVE DISORDER SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID GLUCOSE METABOLIC RATES; CEREBRAL BLOOD-FLOW; CLOMIPRAMINE TREATMENT; SEROTONERGIC RESPONSIVITY; M-CHLOROPHENYLPIPERAZINE; IMIPRAMINE BINDING; LESIONS; INTERFERENCE; DEPRESSION; FLUOXETINE C1 NIMH, NEUROPHYSIOL LAB, POOLESVILLE, MD USA. NR 57 TC 54 Z9 54 U1 2 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1992 VL 15 IS 4 BP 813 EP 824 PG 12 WC Psychiatry SC Psychiatry GA KZ892 UT WOS:A1992KZ89200008 PM 1461798 ER PT J AU STEINER, H HUSTON, JP AF STEINER, H HUSTON, JP TI CONTROL OF TURNING BEHAVIOR UNDER APOMORPHINE BY SENSORY INPUT FROM THE FACE SO PSYCHOPHARMACOLOGY LA English DT Article DE APOMORPHINE; TURNING BEHAVIOR; SENSORY IMBALANCE; SENSORY RESPONSIVENESS; DOPAMINE ID PERIORAL BITING REFLEX; SUBSTANTIA NIGRA; SNOUT CONTACT; GABA-AGONIST; ASYMMETRIES; RATS; INJECTION; ROTATION; RECOVERY; HEMIVIBRISSOTOMY AB It has been shown that peripheral manipulation of sensory input by removal of vibrissae on one side of the rat's face induces turning behavior which is directcd towards the contralateral vibrissae-intact side, under the influence of the dopamine receptor agonist apomorphine. In the present experiment, we examined whether rats under apomorphine turn towards the side with more sensory input, or simply away from the manipulated side. Thus, an experimental manipulation was designed to increase sensory input. Sensory stimulation was applied by attaching a clip into the fur on one side of the face. Rats injected with apomorphine in doses of 0.5-5.0 mg/kg (but not with 0.05 mg/kg or vehicle) exhibited turning behavior towards the side of the clip. This sensory stimulation was also found to influence spontaneous behavioral asymmetries. These results show that an imbalance in sensory input is sufficient to produce turning under apomorphine. C1 UNIV DUSSELDORF,INST PHYSIOL PSYCHOL 1,W-4000 DUSSELDORF 1,GERMANY. RP STEINER, H (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 2D-10,BETHESDA,MD 20892, USA. RI Huston, Joseph/C-8986-2009 NR 29 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1992 VL 109 IS 4 BP 390 EP 394 DI 10.1007/BF02247713 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA KB814 UT WOS:A1992KB81400002 PM 1365852 ER PT J AU TERRY, P KATZ, JL AF TERRY, P KATZ, JL TI DIFFERENTIAL ANTAGONISM OF THE EFFECTS OF DOPAMINE D1-RECEPTOR AGONISTS ON FEEDING-BEHAVIOR IN THE RAT SO PSYCHOPHARMACOLOGY LA English DT Article DE DOPAMINE; D1; D2; SKF-38393; SKF-77434; SKF-82958; SCH-23390; SPIPERONE; FEEDING; BEHAVIOR; RAT ID RECEPTOR AGONISTS; SELECTIVE D-1; THIENOPYRIDINE DERIVATIVES; MICROSTRUCTURAL ANALYSIS; D1 ANTAGONIST; SCH 23390; SCH-23390; FOOD; CLASSIFICATION; SK-AND-F-38393 AB A series of experiments was conducted to examine the effects of dopamine D1 receptor agonists on food intake in rats. In the first experiment, the D1 agonist SKF 38393 (3.0 30.0 mg/kg) dose-dependently suppressed feeding during a 40 min food-access period, both in food-deprived rats and in non-deprived rats fed a highly palatable diet. Non-deprived rats were more sensitive to these effects of SKF 38393. Using the limited-access, food-deprivation procedure, a comparison was made between the anorectic effects of three D1 agonists with differing intrinsic efficacies and receptor selectivities. Rank order of potencies for reducing food intake was SKF 82958 > SKF 77434 > SKF 38393 (ED50 values: 0.7, 3.6 and 15.7 mg/kg, respectively). Dose-related, surmountable antagonism by the D1 antagonist SCH 23390 (0.01 and 0.03 mg/kg) was only obtained with SKF 82958 (0.1-10.0 mg/kg). In contrast to the other compounds, the effects of SKF 38393 were not appreciably altered by the D1 antagonist. The effects of SKF 82958 were also antagonized by the D2 receptor antagonist spiperone (0.05 and 0.1 mg/kg), although not in a dose-dependent manner. The present results support a role for D1 receptors in central feeding mechanisms. They also suggest that the effects of SKF 38393 on feeding may not be mediated exclusively by the D1 receptor and, further, that SKF 38393 may not serve well in behavioral studies as a prototypical D1 agonist. The results also demonstrate the need for comparisons among several compounds in studies of D1 mediated behavioral effects. RP TERRY, P (reprint author), NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,POB 5180,BALTIMORE,MD 21224, USA. OI Katz, Jonathan/0000-0002-1068-1159 NR 53 TC 39 Z9 39 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1992 VL 109 IS 4 BP 403 EP 409 DI 10.1007/BF02247715 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA KB814 UT WOS:A1992KB81400004 PM 1365854 ER PT J AU AULAKH, CS HILL, JL YONEY, HT MURPHY, DL AF AULAKH, CS HILL, JL YONEY, HT MURPHY, DL TI EVIDENCE FOR INVOLVEMENT OF 5-HT1C AND 5-HT2 RECEPTORS IN THE FOOD-INTAKE SUPPRESSANT EFFECTS OF 1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE (DOI) SO PSYCHOPHARMACOLOGY LA English DT Article DE METERGOLINE; MESULERGINE; MIANSERIN; SPIPERONE; MDL-72222; PROPRANOLOL; FOOD-DEPRIVED; RITANSERIN ID FAWN-HOODED RATS; RADIOLIGAND BINDING; SEROTONIN RECEPTOR; RECOGNITION SITES; H-3 MESULERGINE; CHOROID-PLEXUS; BRAIN; AGONIST; ANTAGONISTS; RESPONSES AB Administration of various doses of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) to rats produced dose-related decreases in 1-h food intake in the food-deprived paradigm. Pretreatment with spiperone (5-HT1A/5-HT2/D2 antagonist), propranolol or CGP361A (beta-adrenoceptor antagonists that also have binding affinities for 5-HT1A and 5-HT1B sites) and MDL-72222 (5-HT3 antagonist) did not attenuate DOI-induced suppression of food intake. In contrast, pretreatment with metergoline (5-HT1/5-HT2 antagonist) completely blocked whereas mesulergine, mianserin and ritanserin (5-HT1c/5-HT2 antagonists) partially blocked DOI's effect on food intake. On the other hand, pretreatment with MDL-72222 but not with m-chlorophenylpiperazine (m-CPP) significantly potentiated DOI-induced suppression of food intake. Furthermore, the food intake suppressant effects of various doses of DOI were found to be similar in the Fawn-Hooded (FH) rat strain as compared to the Wistar rat strain. These findings suggest that DOI-induced suppression of food intake is mediated by stimulation of both 5-HT1C and 5-HT2 receptors. RP AULAKH, CS (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 26 Z9 27 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1992 VL 109 IS 4 BP 444 EP 448 DI 10.1007/BF02247721 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA KB814 UT WOS:A1992KB81400010 PM 1365860 ER PT J AU FULHAM, MJ BIZZI, A DIETZ, MJ SHIH, HHL RAMAN, R SOBERING, GS FRANK, JA DWYER, AJ ALGER, JR DICHIRO, G AF FULHAM, MJ BIZZI, A DIETZ, MJ SHIH, HHL RAMAN, R SOBERING, GS FRANK, JA DWYER, AJ ALGER, JR DICHIRO, G TI MAPPING OF BRAIN-TUMOR METABOLITES WITH PROTON MR SPECTROSCOPIC IMAGING - CLINICAL RELEVANCE SO RADIOLOGY LA English DT Article DE BRAIN, EFFECTS OF IRRADIATION ON; BRAIN NEOPLASMS, CT; BRAIN NEOPLASMS, MR; BRAIN NEOPLASMS, THERAPEUTIC RADIOLOGY; EMISSION CT; MAGNETIC RESONANCE (MR), SPECTROSCOPY ID MAGNETIC-RESONANCE SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; F-18 FLUORODEOXYGLUCOSE; INTRACRANIAL TUMORS; GLUCOSE-UTILIZATION; INVIVO; NMR; PET; DIFFERENTIATION; CHEMOTHERAPY AB Brain tumor metabolism was studied with hydrogen-1 magnetic resonance spectroscopy and positron emission tomography with fluorine-18 fluorodeoxyglucose in 50 patients. N-acetylaspartate (NAA) was generally decreased in tumors and radiation necrosis but was somewhat preserved at neoplasm margins. Choline was increased in most solid tumors. Solid high-grade gliomas had higher normalized choline values than did solid low-grade gliomas (P < .02), but the normalized choline value was not a discriminator of tumor grade, since necrotic high-grade lesions had reduced choline values. Serial studies in one case showed an increase in choline as the glioma underwent malignant degeneration. Choline values were lower in chronic radiation necrosis than in solid anaplastic tumors (P < .001). In two cases studied before and after treatment, clinical improvement and a reduction in choline followed therapy. Lactate is more likely to be found in high-grade gliomas, but its presence is not a reliable indicator of malignancy. C1 NINCDS,DIAGNOST RADIOL RES PROGRAM,NEUROIMAGING BRANCH,RM 1C451,BLDG 10,BETHESDA,MD 20892. NINCDS,NMR RES CTR,BETHESDA,MD 20892. NINCDS,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RI Bizzi, Alberto/K-3141-2016 OI Bizzi, Alberto/0000-0002-0253-5274 NR 41 TC 286 Z9 299 U1 1 U2 8 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1992 VL 185 IS 3 BP 675 EP 686 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JZ347 UT WOS:A1992JZ34700015 PM 1438744 ER PT J AU ROSENTHAL, DI BARTON, NW MCKUSICK, KA ROSEN, BR HILL, SC CASTRONOVO, FP BRADY, RO DOPPELT, SH MANKIN, HJ AF ROSENTHAL, DI BARTON, NW MCKUSICK, KA ROSEN, BR HILL, SC CASTRONOVO, FP BRADY, RO DOPPELT, SH MANKIN, HJ TI QUANTITATIVE IMAGING OF GAUCHER DISEASE SO RADIOLOGY LA English DT Article DE BONE MARROW, CT; BONES, MR; BONES, RADIONUCLIDE STUDIES; GAUCHER DISEASE; SPLEEN, MR; XENON, RADIOACTIVE ID MARROW TRANSPLANTATION; REPLACEMENT THERAPY; BONE; CT AB Twenty-three patients with type 1 Gaucher disease were evaluated with a battery of quantitative imaging techniques. Plain radiographs were used to measure cortical thickness and Erlenmeyer flask deformity. Xenon-133 uptake was measured in scans of the lower extremities. Dual-energy quantitative computed tomography was used for calculation of trabecular bone and bone marrow fat content in the spine and long bones. Magnetic resonance (MR) imaging was performed to evaluate disease extent and three-dimensional splenic volume. MR images were also used to provide quantitative measurements of each vertebral fat fraction. Each imaging modality was correlated with the others as well as with the clinical history of skeletal complications and the hematocrit and acid phosphatase activity. There was a strong relationship between splenic volume and severity as measured clinically and with laboratory testing. The spinal fat fraction also correlated with these measures of disease severity and with the femoral fat fraction and xenon uptake. No measurement allowed discrimination of patients with from those without skeletal complications. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED,BOSTON,MA 02114. NIH,BETHESDA,MD 20892. RP ROSENTHAL, DI (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,15 PARKMAN ST,SUITE 515,BOSTON,MA 02114, USA. NR 19 TC 51 Z9 52 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 DEC PY 1992 VL 185 IS 3 BP 841 EP 845 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JZ347 UT WOS:A1992JZ34700048 PM 1438773 ER PT J AU NEGENDANK, WG BROWN, TR EVELHOCH, JL GRIFFITHS, JR LIOTTA, LA MARGULIS, AR MORRISETT, JD ROSS, BD SHTERN, F AF NEGENDANK, WG BROWN, TR EVELHOCH, JL GRIFFITHS, JR LIOTTA, LA MARGULIS, AR MORRISETT, JD ROSS, BD SHTERN, F TI PROCEEDINGS OF A NATIONAL CANCER INSTITUTE WORKSHOP - MR SPECTROSCOPY AND TUMOR-CELL BIOLOGY SO RADIOLOGY LA English DT Article DE MAGNETIC RESONANCE (MR), SPECTROSCOPY; NEOPLASMS, DIAGNOSIS; NEOPLASMS, MR; NEOPLASMS, RADIONUCLIDE STUDIES AB In December 1991, the National Cancer Institute held a workshop to evaluate the role of magnetic resonance (MR) spectroscopy in human cancer biology. The clinical and basic cancer research issues requiring use of MR spectroscopy, the advantages and limitations of MR spectroscopy, and future directions in MR spectroscopy of cancer were discussed. Consensus-building panels were formed on the following four topics: cell membrane biochemistry, tumor therapeutic response or drug resistance, appropriate model systems, and potential clinical applications of MR spectroscopy. The workshop members concluded that large prospective clinical studies as well as in vivo animal and human studies to define prognostic variables should be performed, with correlation between MR spectroscopic results and biochemical and physiologic features. Studies of phospholipid metabolism, the pharmacokinetics of anticancer agents, and effects of new cancer treatments on the tumor vasculature and normal tissues are needed. C1 FOX CHASE CANC CTR,NMR DEPT,PHILADELPHIA,PA 19111. WAYNE STATE UNIV,DEPT MED,DETROIT,MI 48202. ST GEORGE HOSP,DIV BIOCHEM,LONDON,ENGLAND. NCI,PATHOL LAB,ROCKVILLE,MD 20852. NCI,DIAGNOST IMAGING RES BRANCH,ROCKVILLE,MD. UNIV CALIF SAN FRANCISCO,DEPT RADIOL,SAN FRANCISCO,CA 94143. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. HUNTINGTON MED RES INST,PASADENA,CA. RI Griffiths, John/F-2853-2010 NR 0 TC 26 Z9 26 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1992 VL 185 IS 3 BP 875 EP 883 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JZ347 UT WOS:A1992JZ34700054 PM 1438779 ER PT J AU SICHIERI, R DELOLIO, CA CORREIA, VR EVERHART, JE AF SICHIERI, R DELOLIO, CA CORREIA, VR EVERHART, JE TI GEOGRAPHICAL PATTERNS OF PROPORTIONATE MORTALITY FOR THE MOST COMMON CAUSES OF DEATH IN BRAZIL SO REVISTA DE SAUDE PUBLICA LA English DT Article DE MORTALITY, TRENDS; CHRONIC DISEASE, MORTALITY; CAUSE OF DEATH; RESIDENCE CHARACTERISTICS ID CANCER; TRENDS AB Mortality due to chronic diseases has been increasing in all regions of Brazil with corresponding decreases in mortality from infectious diseases. The geographical variation in proportionate mortality for chronic diseases for 17 Brazilian state capitals for the year 1985 and their association with socio-economic variables and infectious disease was studied. Calculations were made of correlation coefficients of proportionate mortality for adults of 30 years or above due to ischaemic heart disease, stroke and cancer of the lung, the breast and stomach with 3 socio-economic variables, race, and mortality due to infectious disease. Linear regression analysis included as independent variables the % of illiteracy, % of whites, % of houses with piped water, mean income, age group, sex, and % of deaths caused by infectious disease. The dependent variables were the % of deaths due to each one of the chronic diseases studied by age-sex group. Chronic diseases were an important cause of death in all regions of Brazil. Ischaemic heart diseases, stroke and malignant neoplasms accounted for more than 34% of the mortality in each of the 17 capitals studied. Proportionate cause-specific mortality varied markedly among state capitals. Ranges were 6.3-19.5% for ischaemic heart diseases, 8.3-25.4% for stroke, 2.3-10.4% for infections and 12.2-21.5% for malignant neoplasm. Infectious disease mortality had the highest (p < 0.001) correlation with all the four socio-economic variables studied and ischaemic heart disease showed the second highest correlation (p < 0.05). Higher socio-economic level was related to a lower % of infectious diseases and a higher % of ischaemic heart diseases. Mortality due to breast cancer and stroke was not associated with socio-economic variables. Multivariate linear regression models explained 59% of the variance among state capitals for mortality due to ischaemic heart disease, 50% for stroke, 28% for lung cancer, 24% for breast cancer and 40% for stomach cancer. There were major differences in the proportionate mortality due to chronic diseases among the capitals which could not be accounted for by the social and environmental factors and by the mortality due to infectious disease. C1 UNIV ESTADUAL MARINGA,CTR CIENCIAS BIOL & SAUDE,MARINGA,PARANA,BRAZIL. NIDDKD,DIV DIGEST DIS & NUTR,EPIDEMIOL & DATA SYST PROGRAM,WASHINGTON,DC. UNIV SAO PAULO,FAC SAUDE PUBL,SAO PAULO,BRAZIL. NR 21 TC 3 Z9 4 U1 0 U2 1 PU REVISTA DE SAUDE PUBLICA PI SAO PAULO PA FACULDADE SAUDE PUBL DA USP, AV DR ARNALDO 715, 01255 SAO PAULO, BRAZIL SN 0034-8910 J9 REV SAUDE PUBL JI Rev. Saude Publica PD DEC PY 1992 VL 26 IS 6 BP 424 EP 430 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KN051 UT WOS:A1992KN05100008 PM 1342534 ER PT J AU URBA, WJ WILSON, WH DUFFEY, PL WITTES, R CHABNER, BA LONGO, DL AF URBA, WJ WILSON, WH DUFFEY, PL WITTES, R CHABNER, BA LONGO, DL TI RECENT NATIONAL CANCER INSTITUTE LYMPHOMA TRIALS OF ETOPOSIDE-CONTAINING COMBINATION CHEMOTHERAPY SO SEMINARS IN ONCOLOGY LA English DT Article ID LARGE-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; DRUG-RESISTANCE; AGGRESSIVE LYMPHOMA; MULTIPLE-MYELOMA; DOSE INTENSITY; P-GLYCOPROTEIN; DIFFUSE; EXPRESSION; VERAPAMIL C1 NCI,DIV CANC TREATMENT,MED BRANCH,BETHESDA,MD 20892. NCI,DCT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. RP URBA, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNA CORP,CLIN SERV PROGRAM,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 19 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1992 VL 19 IS 6 SU 13 BP 26 EP 32 PG 7 WC Oncology SC Oncology GA KL233 UT WOS:A1992KL23300006 PM 1283467 ER PT J AU GREVER, MR SCHEPARTZ, SA CHABNER, BA AF GREVER, MR SCHEPARTZ, SA CHABNER, BA TI THE NATIONAL-CANCER-INSTITUTE - CANCER DRUG DISCOVERY AND DEVELOPMENT PROGRAM SO SEMINARS IN ONCOLOGY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; I CLINICAL-TRIALS; PHILADELPHIA-CHROMOSOME; NATURAL-PRODUCTS; PHASE-II; ONCOGENE; BCR/ABL; ASSAY; MICE; ABL C1 NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. RP GREVER, MR (reprint author), NCI,DEV THERAPEUT PROGRAM,EXECUT PLAZA N,ROOM 843,BETHESDA,MD 20892, USA. NR 53 TC 554 Z9 555 U1 1 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1992 VL 19 IS 6 BP 622 EP 638 PG 17 WC Oncology SC Oncology GA KC785 UT WOS:A1992KC78500003 PM 1462164 ER PT J AU ROWINSKY, EK ONETTO, N CANETTA, RM ARBUCK, SG AF ROWINSKY, EK ONETTO, N CANETTA, RM ARBUCK, SG TI TAXOL - THE 1ST OF THE TAXANES, AN IMPORTANT NEW CLASS OF ANTITUMOR AGENTS SO SEMINARS IN ONCOLOGY LA English DT Article ID HAMSTER OVARY CELLS; RESISTANT MUTANTS; CROSS-RESISTANCE; BREAST-CANCER; PHASE-I; GROWTH; DRUG; NEUROPATHY; RP-56976; TAXOTERE C1 BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. RP ROWINSKY, EK (reprint author), JOHNS HOPKINS UNIV HOSP,CTR ONCOL,DIV PHARMACOL & EXPTL THERAPEUT,600 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 56 TC 418 Z9 422 U1 1 U2 22 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1992 VL 19 IS 6 BP 646 EP 662 PG 17 WC Oncology SC Oncology GA KC785 UT WOS:A1992KC78500005 PM 1361079 ER PT J AU CHESON, BD AF CHESON, BD TI NEW ANTIMETABOLITES IN THE TREATMENT OF HUMAN MALIGNANCIES SO SEMINARS IN ONCOLOGY LA English DT Review ID HAIRY-CELL LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; PHASE-II TRIAL; DEAMINASE INHIBITOR 2'-DEOXYCOFORMYCIN; CONTINUOUS-INFUSION SCHEDULE; ACUTE MYELOGENOUS LEUKEMIA; LOW-DOSE DEOXYCOFORMYCIN; NERVOUS-SYSTEM TOXICITY RP CHESON, BD (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH,MED SECT,BETHESDA,MD 20892, USA. NR 137 TC 52 Z9 52 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1992 VL 19 IS 6 BP 695 EP 706 PG 12 WC Oncology SC Oncology GA KC785 UT WOS:A1992KC78500009 PM 1361080 ER PT J AU CHRISTIAN, MC AF CHRISTIAN, MC TI THE CURRENT STATUS OF NEW PLATINUM ANALOGS SO SEMINARS IN ONCOLOGY LA English DT Article ID HUMAN OVARIAN-CANCER; ENTRAPPED CIS-BIS-NEODECANOATO-TRANS-R,R-1,2-DIAMINOCYCLOHEXANE PLATINUM(II); CARCINOMA CELL-LINES; PHASE-I; ANTITUMOR-ACTIVITY; CISPLATIN NEUROTOXICITY; CIRCADIAN-RHYTHM; LIVER METASTASES; NUDE-MICE; TETRAPLATIN RP CHRISTIAN, MC (reprint author), NCI,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892, USA. NR 91 TC 98 Z9 99 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1992 VL 19 IS 6 BP 720 EP 733 PG 14 WC Oncology SC Oncology GA KC785 UT WOS:A1992KC78500011 PM 1462169 ER PT J AU PARKINSON, DR SMITH, MA CHESON, BD STEVENSON, HC FRIEDMAN, MA AF PARKINSON, DR SMITH, MA CHESON, BD STEVENSON, HC FRIEDMAN, MA TI TRANS-RETINOIC ACID AND RELATED DIFFERENTIATION AGENTS SO SEMINARS IN ONCOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; CELL LINE HL-60; SYNERGISTICALLY INDUCE DIFFERENTIATION; INDUCED GROWTH-INHIBITION; NON-LYMPHOCYTIC LEUKEMIA; TUMOR NECROSIS FACTOR; NEURO-BLASTOMA CELLS; PHASE-II TRIAL; 13-CIS-RETINOIC ACID; PRIMARY CULTURE RP PARKINSON, DR (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,EPN 715,BETHESDA,MD 20892, USA. NR 90 TC 26 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1992 VL 19 IS 6 BP 734 EP 741 PG 8 WC Oncology SC Oncology GA KC785 UT WOS:A1992KC78500012 PM 1462170 ER PT J AU OLEARY, DH POLAK, JF KRONMAL, RA KITTNER, SJ BOND, MG WOLFSON, SK BOMMER, W PRICE, TR GARDIN, JM SAVAGE, PJ AF OLEARY, DH POLAK, JF KRONMAL, RA KITTNER, SJ BOND, MG WOLFSON, SK BOMMER, W PRICE, TR GARDIN, JM SAVAGE, PJ TI DISTRIBUTION AND CORRELATES OF SONOGRAPHICALLY DETECTED CAROTID-ARTERY DISEASE IN THE CARDIOVASCULAR HEALTH STUDY SO STROKE LA English DT Article DE AGED; CAROTID ARTERY DISEASES; EPIDEMIOLOGY; ULTRASONICS ID B-MODE ULTRASOUND; POPULATION-BASED ULTRASONOGRAPHY; RISK-FACTORS; PLAQUE DISTRIBUTION; HEART-DISEASE; ATHEROSCLEROSIS; STENOSIS; DETERMINANTS; ANGIOGRAPHY; VARIABILITY AB Background and Purpose: This article describes the prevalence of extracranial carotid atherosclerosis assessed by ultrasonography, its association with risk factors, and its relation to symptomatic coronary disease and stroke in men and women aged greater-than-or-equal-to 65 years. Methods: Maximum percent stenosis, maximum common carotid artery wall thickness, and maximum internal carotid artery wall thickness were assessed using duplex ultrasound in 5,201 men and women aged greater-than-or-equal-to 65 years in the Cardiovascular Health Study, a study of the risk factors and natural history of cardiovascular disease in the elderly. Existing coronary disease and stroke were assessed by physical examination and participant history. Results: Detectable carotid stenosis was present in 75% of men and 62% of women, although the prevalence of greater-than-or-equal-to 50% stenosis was low, 7% in men and 5% in women. Maximum stenosis and maximum wall thickness measurements increased with age and were uniformly greater at all ages in men than in women (p<0.00001). Established risk factors for atherosclerosis (hypertension, smoking, diabetes) and indications of vascular disease (left ventricular hypertrophy, major electrocardiographic abnormality, bruits, and history of heart disease or stroke) related to all three carotid artery measures in the the elderly. Of the three ultrasound measures, the best correlate for a history of coronary disease was maximum internal carotid artery wall thickness. For stroke the best correlate was common carotid artery wall thickness. Multiple logistic regression models of prevalent coronary heart disease and stroke that included the ultrasound findings indicated, after adjustment for age and sex, that maximum internal wall thickness and maximum common carotid wall thickness were significant correlates of both. Maximum stenosis did not add significantly to the correlation. Conclusions. In the elderly the incidence of carotid atherosclerosis was high, although the frequency of severe disease was low. The prevalence and severity of carotid atherosclerosis continued to increase with age even in the late decades of life, and more disease was found in men than in women at all ages. Known risk factors for atherosclerosis continued to relate to carotid abnormalities in the later decades of life, both in symptomatic and asymptomatic subjects. C1 GEISINGER MED CTR,DIV RADIOL,DANVILLE,PA 17822. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT ANAT,WINSTON SALEM,NC 27103. UNIV PITTSBURGH,DEPT NEUROSURG,PITTSBURGH,PA 15260. UNIV CALIF DAVIS,SACRAMENTO MED CTR,DEPT MED,SACRAMENTO,CA 95817. UNIV CALIF IRVINE,IRVINE,CA 92717. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. FU NHLBI NIH HHS [N0 1-HC85079, N0 1-HC85086] NR 37 TC 612 Z9 633 U1 1 U2 7 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1992 VL 23 IS 12 BP 1752 EP 1760 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA KA151 UT WOS:A1992KA15100010 PM 1448826 ER PT J AU ZEIGER, MA PASS, HI DOPPMAN, JD NIEMAN, LK CHROUSOS, GP CUTLER, GB JENSEN, RT NORTON, JA UDELSMAN, R PRINZ, R AUN, F KINDER, B THOMPSON, N CLARK, O AF ZEIGER, MA PASS, HI DOPPMAN, JD NIEMAN, LK CHROUSOS, GP CUTLER, GB JENSEN, RT NORTON, JA UDELSMAN, R PRINZ, R AUN, F KINDER, B THOMPSON, N CLARK, O TI SURGICAL STRATEGY IN THE MANAGEMENT OF NON-SMALL-CELL ECTOPIC ADRENOCORTICOTROPIC HORMONE SYNDROME SO SURGERY LA English DT Article; Proceedings Paper CT 13TH ANNUAL MEETING OF THE AMERICAN ASSOC OF ENDOCRINE SURGEONS CY APR 12-14, 1992 CL MIAMI, FL SP AMER ASSOC ENDOCRINE SURGEONS ID CUSHINGS-SYNDROME; DIAGNOSIS AB Background. Non-small cell ectopic adrenocorticotropic hormone (ACTH) syndrome is a rare cause of hypercortisolism that may require surgery for either curative resection or palliative adrenalectomy. Methods. We report our surgical experience with 41 patients with ectopic ACTH syndrome and no evidence of small cell lung cancer at initial evaluation. Results. All 41 patients had documented hypercortisolism secondary to ectopic production of ACTH. Based on imaging study results, we determined that 21 patients had localised/resectable disease; eight patients had metastatic disease, and 12 patients had occult disease at examination. Of the 21 patients with localized disease, 16 (76%) were cured of ectopic ACTH by surgery (15 bronchial carcinoid, one pheochromocytoma). Patients with bronchial carcinoid had the greatest probability for cure of ectopic ACTH syndrome, and patients with thoracic primary tumor were more likely to be cured than patients with abdominal primaries. Of the eight patients had metastatic disease, none were cured of the disease; five patients underwent bilateral adrenalectomy, and three patients were given medical therapy. Only one patient was alive after 5 years. Of the 12 patients who had occult disease, four patients were eventually cured of the disease (three bronchial carcinoid, one thymic carcinoid); one patient died of disease (small cell lung cancer), and seven patients still have occult disease. Nine of 12 patients with occult disease underwent bilateral adrenalectomy for surgical management of hypercortisolism. Conclusions. This study suggests that the most common primary focus of ectopic ACTH production is within the thorax with 25 of 34 (74%) identifiable tumors originating within either the thymus or bronchus. Adrenalectomy offers excellent palliation of hypercortisolism secondary to either occult or metastatic disease. Patients who initially have localized disease usually have bronchial carcinoids and have a high probability of cure with surgical resection (81%). C1 NIH,DIGEST DIS BRANCH DIABET & DIGEST & KIDNEY DIS,BETHESDA,MD 20892. NCI,SURG METAB SECT,BETHESDA,MD 20892. NCI,THORAC ONCOL SECT,SURG BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD. NR 8 TC 23 Z9 23 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1992 VL 112 IS 6 BP 994 EP 1001 PG 8 WC Surgery SC Surgery GA KB293 UT WOS:A1992KB29300005 PM 1333646 ER PT J AU THOM, AK NORTON, JA DOPPMAN, JL MILLER, DL CHANG, R JENSEN, RT VANHEERDEN, J WOLTERING, E SAXE, A THOMPSON, N PRINZ, RA AF THOM, AK NORTON, JA DOPPMAN, JL MILLER, DL CHANG, R JENSEN, RT VANHEERDEN, J WOLTERING, E SAXE, A THOMPSON, N PRINZ, RA TI PROSPECTIVE-STUDY OF THE USE OF INTRAARTERIAL SECRETIN INJECTION AND PORTAL VENOUS SAMPLING TO LOCALIZE DUODENAL GASTRINOMAS SO SURGERY LA English DT Article; Proceedings Paper CT 13TH ANNUAL MEETING OF THE AMERICAN ASSOC OF ENDOCRINE SURGEONS CY APR 12-14, 1992 CL MIAMI, FL SP AMER ASSOC ENDOCRINE SURGEONS ID ZOLLINGER-ELLISON SYNDROME; RESECTION; CALCIUM AB Background. Duodenal gastrinomas producing Zollinger-Ellison syndrome (ZES) are rarely imaged on preoperative studies. Measurement of serum gastrin levels by transhepatic portal venous sampling (PVS) or by sampling from hepatic veins after intraarterial secretin injection have been advocated as useful tests to identify these tumors before operation. Methods. As part of a prospective study, selective intraarterial secretin injection has been performed in 36 consecutive patients with ZES, PVS has been performed in 30 of these patients, and the results have been compared. Results. Gastrinomas were found at laparotomy in 33 of 36 patients (92%). Duodenal tumors were found in 18 patients (50%). The remaining patients had liver, pancreatic, or nodal disease (n = 15). Thirty-two of 36 patients (89%) had positive results with intraarterial secretin injection study, whereas 18 of 30 (60%) had a positive PVS gradient (p = 0.02, Fisher's exact test). The most common positive gradient with intraarterial secretin injection was found with injections of the gastroduodenal artery, and the most common positive gradient with PVS was found in the inferior pancreaticoduodenal (IPDV) or superior pancreaticoduodenal vein (SPDV). Fourteen of 18 (78%) patients with duodenal gastrinomas had a positive GDA injection, whereas five of 18 (28%) without duodenal tumors had a positive GDA injection (p = 0.006). Five of 16 patients with duodenal gastrinomas had a positive gradient in the IPDV or SPDV, whereas four of 14 without duodenal tumors had a positive gradient in the IPDV or SPDV (not significant). Conclusions. Intraarterial secretin injection is more sensitive than PVS at localizing duodenal gastrinomas and should replace PVS in patients with ZES and occult tumors. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NIDDKD,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD. NR 19 TC 56 Z9 56 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1992 VL 112 IS 6 BP 1002 EP 1009 PG 8 WC Surgery SC Surgery GA KB293 UT WOS:A1992KB29300006 PM 1455303 ER PT J AU CARTY, SE JENSEN, RT NORTON, JA ELLISON, C TALPOS, G KAPLAN, EL MODLIN, I AF CARTY, SE JENSEN, RT NORTON, JA ELLISON, C TALPOS, G KAPLAN, EL MODLIN, I TI PROSPECTIVE-STUDY OF AGGRESSIVE RESECTION OF METASTATIC PANCREATIC ENDOCRINE TUMORS SO SURGERY LA English DT Article; Proceedings Paper CT 13TH ANNUAL MEETING OF THE AMERICAN ASSOC OF ENDOCRINE SURGEONS CY APR 12-14, 1992 CL MIAMI, FL SP AMER ASSOC ENDOCRINE SURGEONS ID ISLET CELL TUMORS; MALIGNANT GASTRINOMA; SURGERY; CARCINOMA AB Background. Because metastatic pancreatic endocrine tumors (MPET) have a poor prognosis, 17 patients with potentially resectable MPET were prospectively studied to define the efficacy of aggressive resection. Methods. Patients underwent resection when the full extent of MPET was deemed operable after imaging studies were obtained. Two patients underwent three reoperations for recurrent tumor. Results. MPET were completely excised in 16 of 20 cases by major resections of liver, viscera, and nodes, with no operative mortality. Survival was 87% at 2 years and 79% at 5 years with mean follow-up of 3.2 years. Median imaging disease-free interval was 1.8 years, and four of 17 patients remain biochemically cured. After aggressive resection patients with MPET limited in extent had higher survival than patients with extensive MPET (p < 0.019). In a nonrandomized cohort of 25 patients with inoperable tumor, survival was 60% at 2 years and 28% at 5 years. Conclusions. In select patients MPET can be resected safely with a favorable outcome; most patients will experience recurrence, but some may be cured. Resection of extensive MPET does not appear to improve survival. Resection of limited MPET should be considered as life-extending and potentially curative therapy. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NIADDKD,BETHESDA,MD 20892. NR 25 TC 112 Z9 113 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1992 VL 112 IS 6 BP 1024 EP 1032 PG 9 WC Surgery SC Surgery GA KB293 UT WOS:A1992KB29300009 PM 1455305 ER PT J AU LANGE, JR STEINBERG, SM DOHERTY, GM LANGSTEIN, HN WHITE, DE SHAWKER, TH EASTMAN, RC JENSEN, RT NORTON, JA ANDERSEN, DK PROYE, C RASTAD, J PUARTE, B CLARK, O WEBER, C AF LANGE, JR STEINBERG, SM DOHERTY, GM LANGSTEIN, HN WHITE, DE SHAWKER, TH EASTMAN, RC JENSEN, RT NORTON, JA ANDERSEN, DK PROYE, C RASTAD, J PUARTE, B CLARK, O WEBER, C TI A RANDOMIZED, PROSPECTIVE TRIAL OF POSTOPERATIVE SOMATOSTATIN ANALOG IN PATIENTS WITH NEUROENDOCRINE TUMORS OF THE PANCREAS SO SURGERY LA English DT Article; Proceedings Paper CT 13TH ANNUAL MEETING OF THE AMERICAN ASSOC OF ENDOCRINE SURGEONS CY APR 12-14, 1992 CL MIAMI, FL SP AMER ASSOC ENDOCRINE SURGEONS ID OCTREOTIDE SMS 201-995; CARCINOID-SYNDROME; SMS-201-995; FISTULAS; SECRETION; SANDOSTATIN; RELEASE AB Background. Pancreatic surgery is not uncommonly complicated by prolonged pancreatic drainage and fistula. Octreotide decreases pancreatic exocrine function and has been reported to improve closure of pancreatic and intestinal fistulae. This randomized, prospective trial was designed to evaluate the efficacy of postoperative octreotide in reducing pancreatic drainage and complications after resection of neuroendocrine tumors of the pancreas. Methods. Patients with neuroendocrine tumors of the pancreas were entered into the study and randomized after operation to receive octreotide 150 mug subcutaneously every 8 hours or saline solution subcutaneously every 8 hours in a double-blinded fashion. Daily pancreatic drainage, total drainage, number of days to drain removal, and complications were recorded. Results. Ten patients were given octreotide; eleven patients were given saline solution. The number of days to drain removal, daily drainage, and total drainage were not significantly different. Complications related to pancreatic drainage were not significantly different. Conclusions. Octreotide is not indicated for the routine postoperative management of patients with neuroendocrine tumors of the pancreas. C1 NCI,SURG METAB SECT,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIDDKD,CTR CLIN,DEPT RADIOL,DIGEST DIS BRANCH,BETHESDA,MD. NR 20 TC 20 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 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1992 VL 112 IS 6 BP 1033 EP 1038 PG 6 WC Surgery SC Surgery GA KB293 UT WOS:A1992KB29300010 PM 1455306 ER PT J AU LUSTER, MI PAIT, DG PORTIER, C ROSENTHAL, GJ GERMOLEC, DR COMMENT, CE MUNSON, AE WHITE, K POLLOCK, P AF LUSTER, MI PAIT, DG PORTIER, C ROSENTHAL, GJ GERMOLEC, DR COMMENT, CE MUNSON, AE WHITE, K POLLOCK, P TI QUALITATIVE AND QUANTITATIVE EXPERIMENTAL-MODELS TO AID IN RISK ASSESSMENT FOR IMMUNOTOXICOLOGY SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 6TH INTERNATIONAL CONGRESS OF TOXICOLOGY : TOXICOLOGY FROM DISCOVERY AND EXPERIMENTATION TO THE HUMAN PERSPECTIVE CY JUN 28-JUL 03, 1992 CL ROME, ITALY DE RISK ASSESSMENT; IMMUNOTOXICOLOGY; QUANTITATIVE ANALYSIS AB We have previously reported on the design and content of a screening battery using a ''tier'' approach for detecting potential immunosuppressive compounds in mice [1]. This battery was composed of various immune function, immunopathology and host resistance tests, the results of which could help establish the potential of chemical and biological agents to cause immunosuppression. The data from these studies, which now encompass over 50 compounds, have been analyzed in an attempt to improve future testing strategies and provide information to aid in the risk assessment process. Specifically, the following two issues will be addressed; what are the likelihood(s) for each of the individual tests and testing configurations to accurately identify immunotoxic compounds? and what are the quantitative and qualitative relationships between the immune tests and host resistance assays? C1 NIEHS,BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOSTAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL TOXICOL,RICHMOND,VA 23298. RP LUSTER, MI (reprint author), NIEHS,SYST TOXIC BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 7 TC 28 Z9 28 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC PY 1992 VL 64-5 SI SI BP 71 EP 78 DI 10.1016/0378-4274(92)90174-I PG 8 WC Toxicology SC Toxicology GA KE526 UT WOS:A1992KE52600009 PM 1471226 ER PT J AU PARENTEAU, GL DIRBAS, FM GARMESTANI, K BRECHBIEL, MW BUKOWSKI, MA GOLDMAN, CK CLARK, R GANSOW, OA WALDMANN, TA AF PARENTEAU, GL DIRBAS, FM GARMESTANI, K BRECHBIEL, MW BUKOWSKI, MA GOLDMAN, CK CLARK, R GANSOW, OA WALDMANN, TA TI PROLONGATION OF GRAFT-SURVIVAL IN PRIMATE ALLOGRAFT TRANSPLANTATION BY YTTRIUM-90-LABELED ANTI-TAC IN CONJUNCTION WITH GRANULOCYTE COLONY-STIMULATING FACTOR SO TRANSPLANTATION LA English DT Article ID RECEPTOR MONOCLONAL-ANTIBODY; HUMAN RENAL-TRANSPLANTATION; HUMAN T-CELLS; INTERLEUKIN-2 RECEPTOR; INVIVO; MICE; Y-90; RADIOIMMUNOTHERAPY; ANTIFERRITIN; CHEMOTHERAPY AB High-affinity IL-2 receptors are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells. To exploit this difference in IL-2R expression, anti-Tac, a murine monoclonal antibody specific for the IL-2Ralpha subunit, was used to inhibit organ allograft rejection. To enhance its effector function, anti-Tac was armed by chelation with yttrium-90, a pure beta-emitting radionuclide. Animals received no immunosuppression (n=5, group I, controls), unmodified anti-Tac (n=5, 1 mg/kg q.o.d., group II), or Y-90-anti-Tac (n=5, 1.6 mCi/kg divided into four doses, group III). The animals in group IV (n=4) were treated identically to those in group III with the exception that 5 mug/kg/dose of granulocyte colony-stimulating factor was administered intramuscularly on the days when the yttrium-90 was given and on postoperative days 12 through 35 in order to reduce hematopoietic toxicity. Mean graft survival +/- S.E.M. for the control group was 8.2+/-0.5 days as compared with 13.8+/-2.1 days (P<0.05) for those monkeys treated with unmodified anti-Tac. Graft survival was further prolonged in animals of group III that received Y-90-anti-Tac, with a mean graft survival of 45.0+/-11.8 days; however, three of the five monkeys retained viable grafts within this group but died secondary to bone marrow suppression. In comparison, the monkeys in group IV that were treated with G-CSF in conjunction with Y-90-anti-Tac had a mean graft survival of 49.2+/-2.9 days. In contrast to group III there were no deaths in the group (IV) receiving G-CSF. Furthermore, animals in group IV had a reduced magnitude and shortened duration of irradiation-induced neutropenia when compared with that observed in group III animals that did not receive G-CSF. Thus, treatment with Y-90-anti-Tac in conjunction with G-CSF may have potential applications in organ transplantation and the treatment of IL-2 receptor-expressing neoplastic diseases. C1 NCI,METAB BRANCH,BLDG 10,RM 4N115,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NHLBI,SURG BRANCH,BETHESDA,MD 20892. RP WALDMANN, TA (reprint author), NCI,METAB BRANCH,BLDG 10,RM 4N115,BETHESDA,MD 20892, USA. NR 43 TC 13 Z9 14 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC PY 1992 VL 54 IS 6 BP 963 EP 968 DI 10.1097/00007890-199212000-00004 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA KD062 UT WOS:A1992KD06200004 PM 1281566 ER PT J AU KOONIN, EV AF KOONIN, EV TI A NEW GROUP OF PUTATIVE RNA HELICASES SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID BINDING PROTEIN; REPLICATION; MOTIF; DNA; RECOMBINATION; SUPERFAMILY; EXPRESSION; SEQUENCE RP NIH, NATL CTR BIOTECHNOL INFORMAT, NATL LIB MED, BLDG 38A, BETHESDA, MD 20892 USA. NR 15 TC 70 Z9 71 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 1992 VL 17 IS 12 BP 495 EP 497 DI 10.1016/0968-0004(92)90338-A PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB060 UT WOS:A1992KB06000006 PM 1471259 ER PT J AU STATES, DJ WALSETH, TF LEE, HC AF STATES, DJ WALSETH, TF LEE, HC TI SIMILARITIES IN AMINO-ACID-SEQUENCES OF APLYSIA ADP-RIBOSYL CYCLASE AND HUMAN LYMPHOCYTE ANTIGEN CD38 SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID CYCLIC METABOLITE; ENZYME; NAD+; TISSUES C1 UNIV MINNESOTA, DEPT PHARMACOL, MINNEAPOLIS, MN 55455 USA. UNIV MINNESOTA, DEPT PHYSIOL, MINNEAPOLIS, MN 55455 USA. RP NIH, NATL LIB MED, BLDG 38A, 8600 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Lee, Hon Cheung/C-4329-2009 NR 11 TC 197 Z9 199 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD DEC PY 1992 VL 17 IS 12 BP 495 EP 495 DI 10.1016/0968-0004(92)90337-9 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB060 UT WOS:A1992KB06000005 PM 1471258 ER PT J AU AITKEN, A COLLINGE, DB VANHEUSDEN, BPH ISOBE, T ROSEBOOM, PH ROSENFELD, G SOLL, J AF AITKEN, A COLLINGE, DB VANHEUSDEN, BPH ISOBE, T ROSEBOOM, PH ROSENFELD, G SOLL, J TI 14-3-3 PROTEINS - A HIGHLY CONSERVED, WIDESPREAD FAMILY OF EUKARYOTIC PROTEINS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID KINASE-DEPENDENT ACTIVATOR; TRYPTOPHAN HYDROXYLASES; MOLECULAR-CLONING; TYROSINE; BRAIN; IDENTIFICATION; SEQUENCE; PURIFICATION; INHIBITOR; DATABASE AB A family of proteins known as 14-3-3 is currently receiving increased attention by investigators studying a broad range of biological systems, including plants and invertebrates. The outstanding feature of this family is the extraordinarily high sequence conservation observed. Current thinking indicates that these proteins may function as regulators in signal transduction/phosphorylation mechanisms. C1 ROYAL VET & AGR UNIV,DEPT PLANT BIOL,FREDERIKSBERG,DENMARK. TOKYO METROPOLITAN UNIV,DEPT CHEM,TOKYO 158,JAPAN. LEIDEN UNIV,2300 RA LEIDEN,NETHERLANDS. NICHHD,BETHESDA,MD 20892. UNIV TEXAS,SCH MED,DEPT PHARMACOL,HOUSTON,TX 77225. UNIV KIEL,INST BOT,W-2300 KIEL 1,GERMANY. RP AITKEN, A (reprint author), NATL INST MED RES,PROT STRUCT LAB,THE RIDGEWAY,MILL HILL,LONDON NW7 1AA,ENGLAND. RI Collinge, David B./G-2854-2014 OI Collinge, David B./0000-0003-2690-5820 NR 30 TC 358 Z9 368 U1 1 U2 22 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 DEC PY 1992 VL 17 IS 12 BP 498 EP 501 DI 10.1016/0968-0004(92)90339-B PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB060 UT WOS:A1992KB06000007 PM 1471260 ER PT J AU UHL, GR HARTIG, PR AF UHL, GR HARTIG, PR TI TRANSPORTER EXPLOSION - UPDATE ON UPTAKE SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID DOPAMINE TRANSPORTER; EXPRESSION CLONING C1 SYNAPT PHARMACEUT CORP,PARAMUS,NJ 07652. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RP UHL, GR (reprint author), NIDA,ADDICT RES CTR,BALTIMORE,MD 21224, USA. NR 26 TC 116 Z9 117 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD DEC PY 1992 VL 13 IS 12 BP 421 EP 425 DI 10.1016/0165-6147(92)90133-Q PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KD059 UT WOS:A1992KD05900001 PM 1293865 ER PT J AU BEATTY, LA AF BEATTY, LA TI CHILD-WELFARE - AN AFRICENTRIC PERSPECTIVE - EVERETT,JE, CHIPUNGU,SS, LEASHORE,BR SO URBAN LEAGUE REVIEW LA English DT Book Review RP BEATTY, LA (reprint author), NIDA,PREVENT RES BRANCH,ROCKVILLE,MD 20852, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL URBAN LEAGUE INC PI WASHINGTON PA RESEARCH DEPT 6TH FL 1111 14TH STREET NW, WASHINGTON, DC 20005 SN 0147-1740 J9 URBAN LEAGUE REV PD WIN PY 1992 VL 15 IS 2 BP 97 EP 100 PG 4 WC Ethnic Studies; Sociology; Urban Studies SC Ethnic Studies; Sociology; Urban Studies GA KG122 UT WOS:A1992KG12200009 ER PT J AU MUELLER, RE BAGGIO, L KOZAK, CA BALL, JK AF MUELLER, RE BAGGIO, L KOZAK, CA BALL, JK TI A COMMON INTEGRATION LOCUS IN TYPE-B RETROVIRUS-INDUCED THYMIC LYMPHOMAS SO VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; INDUCED RAT THYMOMAS; MAMMARY-TUMOR VIRUS; MOUSE X-CHROMOSOME; TRANSGENIC MICE; C-MYC; REGION; GENE; DNA; ACTIVATION C1 NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP MUELLER, RE (reprint author), UNIV WESTERN ONTARIO,DEPT BIOCHEM,LONDON N6A 5C1,ONTARIO,CANADA. NR 51 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 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1992 VL 191 IS 2 BP 628 EP 637 DI 10.1016/0042-6822(92)90238-K PG 10 WC Virology SC Virology GA JZ987 UT WOS:A1992JZ98700011 PM 1333116 ER PT J AU SHARPLESS, N GILBERT, D VANDERCAM, B ZHOU, JM VERDIN, E RONNETT, G FRIEDMAN, E DUBOISDALCQ, M AF SHARPLESS, N GILBERT, D VANDERCAM, B ZHOU, JM VERDIN, E RONNETT, G FRIEDMAN, E DUBOISDALCQ, M TI THE RESTRICTED NATURE OF HIV-1 TROPISM FOR CULTURED NEURAL CELLS SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL NERVOUS-SYSTEM; HUMAN GLIAL-CELLS; BRAIN-DERIVED CELLS; T-CELL; PRODUCTIVE INFECTION; GALACTOSYL CERAMIDE; CEREBROSPINAL-FLUID; MICROGLIAL CELLS; AIDS C1 NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. HOWARD HUGHES MED INST,NIH,RES SCHOLARS PROGRAM,BETHESDA,MD 20814. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. UNIV PENN,DEPT NEUROSURG,PHILADELPHIA,PA 19104. OI Verdin, Eric/0000-0003-3703-3183 NR 64 TC 60 Z9 60 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1992 VL 191 IS 2 BP 813 EP 825 DI 10.1016/0042-6822(92)90257-P PG 13 WC Virology SC Virology GA JZ987 UT WOS:A1992JZ98700030 PM 1448925 ER PT J AU LE, SY CHEN, JH SONENBERG, N MAIZEL, JV AF LE, SY CHEN, JH SONENBERG, N MAIZEL, JV TI CONSERVED TERTIARY STRUCTURE ELEMENTS IN THE 5' UNTRANSLATED REGION OF HUMAN ENTEROVIRUSES AND RHINOVIRUSES SO VIROLOGY LA English DT Article ID INTERNAL TRANSLATION INITIATION; RIBOSOMAL FRAMESHIFTING SIGNAL; COMPLETE NUCLEOTIDE-SEQUENCE; POLIOVIRUS MESSENGER-RNA; MOUTH-DISEASE VIRUS; NONTRANSLATED REGION; SECONDARY STRUCTURE; NONCODING REGION; MUTATIONAL ANALYSIS; PROTEIN-SYNTHESIS RP LE, SY (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MATH BIOL LAB,BLDG 469,ROOM 151,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 45 TC 49 Z9 51 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1992 VL 191 IS 2 BP 858 EP 866 DI 10.1016/0042-6822(92)90261-M PG 9 WC Virology SC Virology GA JZ987 UT WOS:A1992JZ98700034 PM 1333125 ER PT J AU MACLEAN, PD AF MACLEAN, PD TI DARWIN ON TRIAL - JOHNSON,PE SO ZYGON LA English DT Book Review RP MACLEAN, PD (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 2 U2 2 PU BLACKWELL PUBLISHERS PI CAMBRIDGE PA 350 MAIN STREET, STE 6, CAMBRIDGE, MA 02148-5023 SN 0591-2385 J9 ZYGON JI Zygon PD DEC PY 1992 VL 27 IS 4 BP 466 EP 469 PG 4 WC Social Issues; Religion SC Social Issues; Religion GA JZ077 UT WOS:A1992JZ07700011 ER PT J AU OBATA, T CHENG, SY AF OBATA, T CHENG, SY TI REGULATION BY THYROID-HORMONE OF THE SYNTHESIS OF A CYTOSOLIC THYROID-HORMONE BINDING-PROTEIN DURING LIVER-REGENERATION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PYRUVATE-KINASE; MONOMER; FRUCTOSE-1,6-BISPHOSPHATE C1 NCI,DCBDC,GENE REGULAT SECT,MOLEC BIOL LAB,BETHESDA,MD 20892. JIKEI UNIV,INST MED SCI,DIV BIOCHEM,TOKYO 105,JAPAN. NR 14 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1992 VL 189 IS 1 BP 257 EP 263 DI 10.1016/0006-291X(92)91552-2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KA513 UT WOS:A1992KA51300037 PM 1449480 ER PT J AU PISEGNA, JR DEWEERTH, A HUPPI, K WANK, SA AF PISEGNA, JR DEWEERTH, A HUPPI, K WANK, SA TI MOLECULAR-CLONING OF THE HUMAN BRAIN AND GASTRIC CHOLECYSTOKININ RECEPTOR - STRUCTURE, FUNCTIONAL EXPRESSION AND CHROMOSOMAL LOCALIZATION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHARMACOLOGICAL CHARACTERIZATION; BOVINE RHODOPSIN; CCK ANTAGONISTS; BINDING; PROTEIN; CELLS; POTENT; LIGAND; CANCER C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NIH,MOLEC GENET SECT,GENET LAB,BETHESDA,MD 20892. NR 34 TC 209 Z9 211 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 30 PY 1992 VL 189 IS 1 BP 296 EP 303 DI 10.1016/0006-291X(92)91557-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KA513 UT WOS:A1992KA51300042 PM 1280419 ER PT J AU GADELHA, FR HANNA, PM MASON, RP DOCAMPO, R AF GADELHA, FR HANNA, PM MASON, RP DOCAMPO, R TI EVIDENCE FOR FREE-RADICAL FORMATION DURING HORSERADISH PEROXIDASE-CATALYZED N-DEMETHYLATION OF CRYSTAL VIOLET SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE CRYSTAL VIOLET; HORSERADISH PEROXIDASE; THIYL RADICAL; ASCORBATE RADICAL; N-DEMETHYLATION; SUPEROXIDE ANION ID GENTIAN-VIOLET; REDUCED GLUTATHIONE; BIOLOGICAL-SYSTEMS; CHRONIC TOXICITY; OXIDATION; ASCORBATE; CARCINOGENICITY; METABOLISM; REDUCTION; BLOOD AB Crystal violet (gentian violet) can undergo an oxidative metabolism, catalyzed by horseradish peroxidase, resulting in formaldehyde formation. The N-demethylation reaction was strongly inhibited by reduced glutathione. Evidence for the formation of a crystal violet radical during the horseradish peroxidase catalyzed reaction was the detection of thiyl and ascorbate radicals from glutathione and ascorbate, respectively. The concentration of radicals from both compounds was significantly increased in the presence of crystal violet. Oxygen uptake was stimulated when glutathione was present in the system and this oxygen uptake was dependent on the dye and enzyme concentration. Oxygen uptake did not occur when ascorbate, instead of glutathione, was present in the system. However, when glutathione was present, ascorbate totally inhibited the glutathione-stimulated oxygen uptake in the crystal violet/horseradish peroxidase/hydrogen peroxide system. Although a weak ESR spectrum from a crystal violet-derived free radical was detected when the dye reacted with H2O2 and horseradish peroxidase, using the fast flow technique, this spectrum could not be interpreted. C1 UNIV ILLINOIS,DEPT VET PATHOBIOL,2001 S LINCOLN AVE,URBANA,IL 61801. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. FU NIAID NIH HHS [AI-23259] NR 32 TC 20 Z9 20 U1 0 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD NOV 30 PY 1992 VL 85 IS 1 BP 35 EP 48 DI 10.1016/0009-2797(92)90051-L PG 14 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA KB646 UT WOS:A1992KB64600004 PM 1333891 ER PT J AU MERRIL, CR AF MERRIL, CR TI ULTRASENSITIVE SILVER STAIN FOR PROTEINS - A CITATION-CLASSIC COMMENTARY ON ULTRASENSITIVE STAIN FOR PROTEINS IN POLYACRYLAMIDE GELS SHOWS REGIONAL VARIATION IN CEREBROSPINAL-FLUID PROTEINS BY MERRIL,C.R., GOLDMAN,D., SEDMAN,S.A., AND EBERT,M.H. SO CURRENT CONTENTS/LIFE SCIENCES LA English DT Article ID ELECTROPHORESIS RP MERRIL, CR (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,BIOCHEM GENET LAB,WASHINGTON,DC 20032, USA. NR 7 TC 0 Z9 0 U1 1 U2 4 PU INST SCI INFORM INC PI PHILADELPHIA PA 3501 MARKET ST, PHILADELPHIA, PA 19104 SN 0011-3409 J9 CC/LIFE SCI PD NOV 30 PY 1992 IS 48 BP 9 EP 9 PG 1 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA JX458 UT WOS:A1992JX45800002 ER PT J AU WANG, RYH SHIH, JWK GRANDINETTI, T PIERCE, PF HAYES, MM WEAR, DJ ALTER, HJ LO, SC AF WANG, RYH SHIH, JWK GRANDINETTI, T PIERCE, PF HAYES, MM WEAR, DJ ALTER, HJ LO, SC TI HIGH-FREQUENCY OF ANTIBODIES TO MYCOPLASMA-PENETRANS IN HIV-INFECTED PATIENTS SO LANCET LA English DT Article ID AIDS; PROTEINS; AGENT AB Mycoplasma penetrans, a novel mycoplasma isolated from HIV-1-infected patients with AIDS, has pathogenic properties associated with in-vivo virulence. Enzyme-linked immunosorbent assay and western blotting detected a more than 100 times higher frequency of antibodies to the mycoplasma in serum from HIV-1-infected patients with AIDS (40%) than from HIV-negative controls (0.3%). Serum from 20% of HIV-1-infected, symptom-free individuals also had M penetrans specific antibodies. The antibodies major immunoreactivity was directed against P35 and P38, the two main lipid-associated membrane protein antigens of the organism. Patients attending sexually transmitted disease clinics had a low frequency of antibody (0.9%). None of 178 HIV-negative patients with different non-AIDS diseases, many associated with immune dysfunction and/or low white cell counts, tested positive for the antibodies. M penetrans, apparently not a commensal and not a simple opportunist, is uniquely associated with HIV-1 infection and AIDS. C1 ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS PATHOL,AMER REGISTRY PATHOL,WASHINGTON,DC 20306. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. AMER RED CROSS,NATL CAPITAL CHAPTER,WASHINGTON,DC. GEORGETOWN UNIV HOSP,HIV CLIN PROGRAM,WASHINGTON,DC 20007. FU NIAID NIH HHS [AI-31830] NR 22 TC 73 Z9 77 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 28 PY 1992 VL 340 IS 8831 BP 1312 EP 1316 DI 10.1016/0140-6736(92)92493-Y PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA KA262 UT WOS:A1992KA26200004 PM 1360035 ER PT J AU HAMILTON, ME MELE, A PERT, A AF HAMILTON, ME MELE, A PERT, A TI STRIATAL EXTRACELLULAR DOPAMINE IN CONSCIOUS VS ANESTHETIZED RATS - EFFECTS OF CHLORAL HYDRATE ANESTHETIC ON RESPONSES TO DRUGS OF DIFFERENT CLASSES SO BRAIN RESEARCH LA English DT Article DE STRIATUM; MICRODIALYSIS; DOPAMINE; CHLORAL HYDRATE; AMPHETAMINE; MORPHINE; RAT ID FREELY MOVING RATS; INVIVO MICRODIALYSIS; NUCLEUS-ACCUMBENS; SUBSTANTIA NIGRA; IMPULSE FLOW; RELEASE; NEURONS; BRAIN; MORPHINE; RESPONSIVENESS AB Many investigations using the microdialysis technique have been performed in anesthetized animals, both in this laboratory and elsewhere. Concern arises with this preparation that the anesthetic may compromise neuronal function, or that it may interact with test drugs affecting neurotransmitter overflow. In addition, in these studies the microdialysis probe typically is introduced into the brain on the day of testing, and data collection commences within an hour or two following probe insertion. It has been suggested that transmitter recovered in the perfusate probably represents leakage due to tissue damage as well as exocytotic release, and may not accurately reflect neuronal responses to the manipulations of interest. Such potential confounds present important implications for the interpretation of data from these studies. The present investigation examined the effects of chloral hydrate anesthetic on (1) basal dopamine (DA) overflow in the anterior striatum, and (2) DA responses to systemically delivered drugs of two different classes known to influence DA activity. Three putative indices of impulse-dependent release were measured: (a) the time course and stability of basal DA overflow over several hours; (b) sodium channel involvement by adding tetrodotoxin (TTX) to the artificial CSF; and (c) calcium channel involvement using magnesium (Mg) in a calcium-free perfusate. Basal DA levels became stable in both conscious and anesthetized preparations by the second hour after probe insertion. Levels of recovered DA overflow in the anterior striata of conscious rats were approximately double those in chloral hydrate-anesthetized rats. Consistent with other findings, this suggests a general depression of CNS function by chloral hydrate. Basal DA was both TTX- and Mg-sensitive, indicating that most of the DA sampled probably arose from exocytotic release. DA response to D-amphetamine differed in the two preparations when expressed as a function of baseline. This reflected both the differences in absolute baseline levels and the impulse-independent mechanism of action of the drug. In contrast, systemic morphine resulted in an increase of DA overflow in anesthetized rats only, an elevation of DOPAC levels in both preparations, and an increase in HVA only in conscious animals. Morphine-treated rats received lower levels of anesthetic supplements over time than did controls, however. Presumably, this resulted in a diminished chloral hydrate suppression both of DA and of metabolite clearance. RP HAMILTON, ME (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,BETHESDA,MD 20892, USA. RI Mele, Andrea/E-7741-2015 NR 30 TC 49 Z9 50 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 27 PY 1992 VL 597 IS 1 BP 1 EP 7 DI 10.1016/0006-8993(92)91498-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA KA290 UT WOS:A1992KA29000001 PM 1477724 ER PT J AU TAKAHAMA, Y SINGER, A AF TAKAHAMA, Y SINGER, A TI POSTTRANSCRIPTIONAL REGULATION OF EARLY T-CELL DEVELOPMENT BY T-CELL RECEPTOR SIGNALS SO SCIENCE LA English DT Article ID 3' UNTRANSLATED REGION; CD8 GENE-EXPRESSION; MESSENGER-RNA; IMMATURE THYMOCYTES; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; V(D)J RECOMBINATION; MURINE THYMOCYTES; TRANSGENIC MICE AB During differentiation in the thymus, immature T cells progress through an ordered sequence of developmental stages that are best characterized by variable expression of the co-receptor molecules CD4 and CD8. Crosslinking of T cell receptor (TCR) molecules on precursor thymocytes was found to block their differentiation into CD4+CD8+ cells by eliminating messenger RNA's encoding two families of developmentally important molecules: the co-receptor molecules CD4 and CD8 and the recombination activating genes 1 and 2. TCR-induced post-transcriptional regulation in early thymocytes was specific for selective messenger RNA's, required protein synthesis, and was itself developmentally regulated. These data identify a post-transcriptional mechanism that is influenced by TCR signals and that regulates early thymocyte development. RP TAKAHAMA, Y (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 63 TC 94 Z9 94 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 NOV 27 PY 1992 VL 258 IS 5087 BP 1456 EP 1462 DI 10.1126/science.1439838 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JZ625 UT WOS:A1992JZ62500021 PM 1439838 ER PT J AU CHATTERJEE, S JOHNSON, PR WONG, KK AF CHATTERJEE, S JOHNSON, PR WONG, KK TI DUAL-TARGET INHIBITION OF HIV-1 INVITRO BY MEANS OF AN ADENOASSOCIATED VIRUS ANTISENSE VECTOR SO SCIENCE LA English DT Article ID TRANS-ACTIVATION; GENE-EXPRESSION; RNA; REPLICATION; CELLS; CLONING; DNA; TRANSDUCTION; INTEGRATION; RESISTANCE AB An adeno-associated virus vector encoding an antisense RNA was used to transduce stable intracellular resistance to human immunodeficiency virus-1 (HIV-1) in human hemopoietic and non-hemopoietic cell lines. The antisense targets are present in all HIV-1 transcripts and include the TAR sequence, which is critical for transcription and virus replication, and the polyadenylation signal. Cell lines expressing antisense RNA showed up to 95 percent inhibition of gene expression directed by the HIV-1 long terminal repeat and greater than 99 percent reduction in infectious HIV-1 production, with no detectable cellular toxicity. Because of their efficient transcription and inability to recombine with HIV-1, adeno-associated virus vectors represent a promising form of anti-retroviral gene therapy. C1 NIAID,VIRAL DIS LAB,ROCKVILLE,MD 20852. GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD. NIAID,INFECT DIS LAB,ROCKVILLE,MD 20852. RI Johnson, Philip/A-6892-2009 NR 37 TC 177 Z9 182 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 27 PY 1992 VL 258 IS 5087 BP 1485 EP 1488 DI 10.1126/science.1359646 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JZ625 UT WOS:A1992JZ62500029 PM 1359646 ER PT J AU DONALDSON, JG FINAZZI, D KLAUSNER, RD AF DONALDSON, JG FINAZZI, D KLAUSNER, RD TI BREFELDIN-A INHIBITS GOLGI MEMBRANE-CATALYZED EXCHANGE OF GUANINE-NUCLEOTIDE ONTO ARF PROTEIN SO NATURE LA English DT Article ID ADP-RIBOSYLATION FACTOR; GTP-BINDING-PROTEIN; TRANSPORT; APPARATUS; VESICLES; COFACTOR; COMPLEX; COP AB THE fungal metabolite brefeldin A is a powerful tool for investigating membrane traffic in eukaryotic cells1. The effects of brefeldin A on traffic are partly explained by its ability to prevent binding of cytosolic coat proteins onto membranes2-5. The non-clathrin coatomer complex6,7 binds reversibly to Golgi membranes in a GTP-controlled cycle8-10. The low-molecular-mass GTP-binding protein ADP-ribosylation factor (ARF), which also associates reversibly with Golgi membranes11,12, is required for coatomer binding13 and probably accounts for the control by guanine nucleotide of the coatomer-membrane interaction. Brefeldin A prevents the assembly of coatomer onto the membrane by inhibiting the GTP-dependent interaction of ARF with the Golgi membrane13, but the nature of this interaction has not been established. Here we demonstrate that Golgi membranes can specifically catalyse the exchange of GTP onto ARF and that brefeldin A prevents this function. RP NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. OI Finazzi, Dario/0000-0001-5176-2839 NR 26 TC 580 Z9 586 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 26 PY 1992 VL 360 IS 6402 BP 350 EP 352 DI 10.1038/360350a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JZ630 UT WOS:A1992JZ63000053 PM 1448151 ER PT J AU FISHER, B REDMOND, C FORD, LG NAYFIELD, SG GREENWALD, P AF FISHER, B REDMOND, C FORD, LG NAYFIELD, SG GREENWALD, P TI SHOULD HEALTHY WOMEN TAKE TAMOXIFEN - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID BREAST; CANCER C1 NCI,BETHESDA,MD 20892. RP FISHER, B (reprint author), UNIV PITTSBURGH,NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA 15261, USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 26 PY 1992 VL 327 IS 22 BP 1596 EP 1597 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JZ432 UT WOS:A1992JZ43200013 ER PT J AU KALINER, M LEMANSKE, R AF KALINER, M LEMANSKE, R TI RHINITIS AND ASTHMA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORTICOSTEROID-DEPENDENT ASTHMA; ALLERGIC RHINITIS; BRONCHIAL-ASTHMA; DRUG-THERAPY; DOUBLE-BLIND; TROLEANDOMYCIN; METHOTREXATE; MECHANISMS C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,SCH MED,DEPT PEDIAT,MADISON,WI 53706. RP KALINER, M (reprint author), NIAID,ALLERG DIS SECT,BETHESDA,MD 20892, USA. NR 60 TC 49 Z9 49 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 25 PY 1992 VL 268 IS 20 BP 2807 EP 2829 DI 10.1001/jama.268.20.2807 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA JY668 UT WOS:A1992JY66800004 PM 1433696 ER PT J AU SAMPSON, HA METCALFE, DD AF SAMPSON, HA METCALFE, DD TI FOOD ALLERGIES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ADVERSE REACTIONS; NATURAL-HISTORY; ATOPIC-DERMATITIS; DIAGNOSIS; HYPERSENSITIVITY; ADDITIVES; CHALLENGE; CHILDREN; INFANCY C1 NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BETHESDA,MD 20892. RP SAMPSON, HA (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,PEDIAT CLIN RES UNIT,BALTIMORE,MD 21205, USA. RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 33 TC 83 Z9 85 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 25 PY 1992 VL 268 IS 20 BP 2840 EP 2844 DI 10.1001/jama.268.20.2840 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JY668 UT WOS:A1992JY66800007 PM 1433699 ER PT J AU STROBER, W JAMES, SP AF STROBER, W JAMES, SP TI THE IMMUNOPATHOGENESIS OF GASTROINTESTINAL AND HEPATOBILIARY DISEASES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CELIAC-DISEASE; PATHOGENESIS; HEPATITIS; ANTIBODY; VIRUS C1 UNIV MARYLAND, DIV GASTROENTEROL, BALTIMORE, MD 21201 USA. RP STROBER, W (reprint author), NIAID, MUCOSAL IMMUN SECT, BETHESDA, MD 20892 USA. NR 29 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 25 PY 1992 VL 268 IS 20 BP 2910 EP 2917 DI 10.1001/jama.268.20.2910 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA JY668 UT WOS:A1992JY66800016 PM 1433708 ER PT J AU LOPEZ, M FLEISHER, T DESHAZO, RD AF LOPEZ, M FLEISHER, T DESHAZO, RD TI USE AND INTERPRETATION OF DIAGNOSTIC IMMUNOLOGICAL LABORATORY TESTS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ANTIBODIES; AUTOANTIBODIES; HEPATITIS; NEUTROPHILS; RELEVANCE; DISORDERS; ONTOGENY; CELLS C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,IMMUNOL SERV,BETHESDA,MD 20892. TULANE UNIV,SCH MED,DEPT MED,DIV RHEUMATOL,NEW ORLEANS,LA 70112. RP LOPEZ, M (reprint author), TULANE UNIV,SCH MED,DEPT MED,DIV ALLERGY & CLIN IMMUNOL,NEW ORLEANS,LA 70112, USA. NR 56 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 25 PY 1992 VL 268 IS 20 BP 2970 EP 2990 DI 10.1001/jama.268.20.2970 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA JY668 UT WOS:A1992JY66800026 PM 1433717 ER PT J AU GREEN, JDF PERHAM, RN ULLRICH, SJ APPELLA, E AF GREEN, JDF PERHAM, RN ULLRICH, SJ APPELLA, E TI CONFORMATIONAL STUDIES OF THE INTERDOMAIN LINKER PEPTIDES IN THE DIHYDROLIPOYL ACETYLTRANSFERASE COMPONENT OF THE PYRUVATE-DEHYDROGENASE MULTIENZYME COMPLEX OF ESCHERICHIA-COLI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYPEPTIDE-CHAIN; PROTEIN; PROLINE; DOMAINS; SEGMENT; MOBILITY; RESIDUES; H-1-NMR; DESIGN; BONDS AB Two peptides (PEP1, 26 residues, and PEP2, 22 residues) were synthesized with amino acid sequences identical to two of the long segments of polypeptide chain rich in alanine, proline, and charged amino acids that link the lipoyl domains together in the dihydrolipoyl acetyltransferase component of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. The circular dichroism and 400-MHz H-1 NMR spectra of the peptides indicated that they lacked regular secondary structure. Even in the presence of 45% (v/v) hexafluoroisopropanol, they appeared to acquire a helical content of only 23-25%. However, C-13 NMR spectroscopy revealed that the Ala-Pro peptide bonds were all (>95%) in the trans configuration, compared with a value of 87% for the Ala-Pro bond in the model peptide AAPA, which is a recurrent sequence motif in PEP1 and PEP2. Likewise in peptides representing the N- and C-terminal halves of peptide PEP2, the Ala-Pro bonds were again all (>95%)-trans, suggesting that peptide length is the essential determinant of the cis:trans ratio. Antisera were raised against peptides PEP2 and PEP3, the latter representing a third interdomain segment of polypeptide chain (Radford, S. E., Laue, E. D., Perham, R. N., Martin, S. R., and Appella, E. (1989a) J. Biol. Chem. 264, 767-775). Despite extensive sequence similarity among peptides PEP1, PEP2, and PEP3, only limited immunological cross-reactivity was observed, which suggests that the antigenic epitope(s) in the peptides are different and distinct. It is likely that these peptides are representative of a class of inter-domain linkers or spacers found in a wide variety of proteins and endowed with varying degrees of flexibility and stiffness to match their particular biological purpose. C1 NCI,CELL BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV CAMBRIDGE,CAMBRIDGE CTR MOLEC RECOGNIT,DEPT BIOCHEM,CAMBRIDGE CB2 1EW,ENGLAND. NR 26 TC 37 Z9 38 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 23484 EP 23488 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900013 PM 1429691 ER PT J AU WASHKO, P LEVINE, M AF WASHKO, P LEVINE, M TI INHIBITION OF ASCORBIC-ACID TRANSPORT IN HUMAN NEUTROPHILS BY GLUCOSE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; FLUORIDE-MEDIATED ACTIVATION; DEHYDROASCORBATE TRANSPORT; ACCUMULATION; PLASMA AB Because of the structural similarity between glucose and ascorbic acid, we investigated the effect of glucose on uptake and accumulation of ascorbic acid in isolated normal human neutrophils. Ascorbic acid accumulation was determined using high-performance liquid chromatography with coulometric electrochemical detection, in conjunction with liquid scintillation spectrometry. Ascorbic acid accumulation in neutrophils is mediated by a high and a low affinity transport activity. In neutrophils from different volunteers, glucose inhibited uptake and accumulation of ascorbic acid by both transport activities 3-9-fold. The mechanism of inhibition was different for each transport activity: inhibition of the high affinity transport activity was noncompetitive, while inhibition of the low affinity activity was competitive. Glucose-induced inhibition of both ascorbic acid transport activities occurred in neutrophils of all donors tested and was fully reversible. Although the mechanism of ascorbic acid accumulation appeared to be different than that for glucose transport, other monosaccharides and glucose transport inhibitors also inhibited ascorbic acid accumulation. These are the first data to suggest that ascorbic acid accumulation in neutrophils can be regulated by compounds of similar structure. C1 NIDDKD,CELL BIOL & GENET LAB,BLDG 8,RM 415,BETHESDA,MD 20892. NR 34 TC 51 Z9 51 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 23568 EP 23574 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900025 PM 1429700 ER PT J AU DEGRAY, JA LASSMANN, G CURTIS, JF KENNEDY, TA MARNETT, LJ ELING, TE MASON, RP AF DEGRAY, JA LASSMANN, G CURTIS, JF KENNEDY, TA MARNETT, LJ ELING, TE MASON, RP TI SPECTRAL-ANALYSIS OF THE PROTEIN-DERIVED TYROSYL RADICALS FROM PROSTAGLANDIN-H SYNTHASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OXIDATION; ENZYME AB We have analyzed the low temperature EPR spectra of the protein-derived tyrosyl radicals detected upon addition of arachidonic acid or 5-phenyl-4-pentenyl-1-hydroperoxide (PPHP) to prostaglandin H synthase. With either arachidonic acid or PPHP the initial radical detected is a doublet (peak-to-trough = 35 Gauss) that disappears rapidly and is replaced by a broad singlet (peak-to-trough = 30 Gauss) followed by a narrow singlet (peak-to-trough = 26.5 Gauss). The relative amounts of these signals vary with time and concentration of arachidonic acid. The three tyrosyl radical signals were subjected to computer simulation and power saturation analysis. The data establish that there are only two distinct tyrosyl radical species, the doublet and the narrow singlet. The broad singlet seen at intermediate times and at low arachidonic acid concentrations is a composite of the doublet and the narrow singlet. The composition of the broad singlet in incubations of prostaglandin H synthase with 0.5 mM arachidonic acid is approximately 40% doublet and 60% singlet. The broad singlet signal does not represent a distinct tyrosyl radical species. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. VANDERBILT UNIV,MED CTR,SCH MED,DEPT BIOCHEM,CTR MOLEC TOXICOL,AB HANCOCK JR MEM LAB CANC RES,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,DEPT CHEM,NASHVILLE,TN 37232. NR 15 TC 76 Z9 76 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 23583 EP 23588 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900027 PM 1331091 ER PT J AU TRIPATHI, RK HEARING, VJ URABE, K AROCA, P SPRITZ, RA AF TRIPATHI, RK HEARING, VJ URABE, K AROCA, P SPRITZ, RA TI MUTATIONAL MAPPING OF THE CATALYTIC ACTIVITIES OF HUMAN TYROSINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IA OCULOCUTANEOUS ALBINISM; SINGLE BASE INSERTION; MAMMALIAN TYROSINASE; GENE MUTATION; DNA; PIGMENTATION; MELANIN; MOUSE; BIOSYNTHESIS; PATIENT AB Tyrosinase (EC 1.14.18.1) is a copper-containing metalloglycoprotein that catalyzes several steps in the melanin pigment biosynthetic pathway; the hydroxylation of tyrosine to L-3,4-dihydroxyphenylalanine (dopa) and the subsequent oxidation of dopa to dopaquinone. It has been proposed that tyrosinase is also able to oxidize 5,6-dihydroxyindole (DHI), a later product in the melanogenic pathway, to indole-5,6-quinone. Tyrosinase enzymatic activity is deficient in patients with classic type I oculocutaneous albinism (OCA), and more than 50 distinct mutations have now been identified in the tyrosinase genes of such patients. To determine the effects of the various tyrosinase gene mutations on the catalytic activities of the enzyme, we carried out site-directed mutagenesis of human tyrosinase cDNA, transiently expressed the mutant cDNAs in transfected HeLa cells, and assayed the resultant encoded proteins for tyrosine hydroxylase, dopa, and DHI oxidase activities, and resulting melanin production. The tyrosine hydroxylase activity of normal tyrosinase is thermostable, whereas its dopa oxidase and DHI oxidase activities are temperature-sensitive. Although all amino acid substitutions tested generally affected the dopa oxidase and DHI oxidase activities in parallel, several exerted distinctly different effects on the tyrosine hydroxylase activities. Together, these results confirm the DHI oxidase activity of mammalian tyrosinase and suggest that the dopa oxidase and DHI oxidase activities of tyrosinase share a common catalytic site, whereas the tyrosine hydroxylase catalytic site is at least partially distinct in the tyrosinase polypeptide. C1 UNIV WISCONSIN,DEPT MED GENET,GENET LAB 317,445 HENRY MALL,MADISON,WI 53706. UNIV WISCONSIN,DEPT PEDIAT,MADISON,WI 53706. NCI,CELL BIOL LAB,BETHESDA,MD 20892. FU NIAMS NIH HHS [AR-39892] NR 46 TC 109 Z9 111 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 23707 EP 23712 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900044 PM 1429711 ER PT J AU CAMERON, CE GRINDE, B JENTOFT, J LEIS, J WEBER, IT COPELAND, TD WLODAWER, A AF CAMERON, CE GRINDE, B JENTOFT, J LEIS, J WEBER, IT COPELAND, TD WLODAWER, A TI MECHANISM OF INHIBITION OF THE RETROVIRAL PROTEASE BY A ROUS-SARCOMA VIRUS PEPTIDE SUBSTRATE REPRESENTING THE CLEAVAGE SITE BETWEEN THE GAG P2 AND P10 PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS-1; MURINE LEUKEMIA-VIRUS; POL POLYPROTEINS; HIV-1 PROTEASE; AVIAN-SARCOMA; TYPE-1 PROTEASE; VIRAL-RNA; SPECIFICITY; RESOLUTION; COMPLEX AB The activity of the avian myeloblastosis virus (AMV) or the human immunodeficiency virus type 1 (HIV-1) protease on peptide substrates which represent cleavage sites found in the gag and gag-pol polyproteins of Rous sarcoma virus (RSV) and HIV-1 has been analyzed. Each protease efficiently processed cleavage site substrates found in their cognate polyprotein precursors. Additionally, in some instances heterologous activity was detected. The catalytic efficiency of the RSV protease on cognate substrates varied by as much as 30-fold. The least efficiently processed substrate, p2-p10, represents the cleavage site between the RSV p2 and p10 proteins. This peptide was inhibitory to the AMV as well as the HIV-1 and HIV-2 protease cleavage of other substrate peptides with K(i) values in the 5-20 muM range. Molecular modeling of the RSV protease with the p2-p10 peptide docked in the substrate binding pocket and analysis of a series of single-amino acid-substituted p2-p10 peptide analogues suggested that this peptide is inhibitory because of the potential of a serine residue in the P1' position to interact with one of the catalytic aspartic acid residues. To open the binding pocket and allow rotational freedom for the serine in P1', there is a further requirement for either a glycine or a polar residue in P2' and/or a large amino acid residue in P3'. The amino acid residues in P1-P4 provide interactions for tight binding of the peptide in the substrate binding pocket. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT BIOCHEM,2119 ABINGTON RD,CLEVELAND,OH 44106. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT PHARMACOL,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [CA38046, CA52047]; PHS HHS [N01 C01 74101] NR 34 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 23735 EP 23741 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900048 PM 1331099 ER PT J AU BUTLER, JD BLANCHETTEMACKIE, J GOLDIN, E ONEILL, RR CARSTEA, G ROFF, CF PATTERSON, MC PATEL, S COMLY, ME COONEY, A VANIER, MT BRADY, RO PENTCHEV, PG AF BUTLER, JD BLANCHETTEMACKIE, J GOLDIN, E ONEILL, RR CARSTEA, G ROFF, CF PATTERSON, MC PATEL, S COMLY, ME COONEY, A VANIER, MT BRADY, RO PENTCHEV, PG TI PROGESTERONE BLOCKS CHOLESTEROL TRANSLOCATION FROM LYSOSOMES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY LIPOPROTEIN; NIEMANN-PICK DISEASE; ACYL-COENZYME-A; MACROPHAGE FOAM CELLS; HAMSTER OVARY CELLS; INTRACELLULAR-TRANSPORT; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; CULTURED FIBROBLASTS; REDUCTASE-ACTIVITY AB Fluorescent microscopic examination of fibroblasts cultured with low density lipoprotein (LDL) and progesterone (10 mug/ml) for 24 h revealed extensive filipin-cholesterol staining of perinuclear lysosomes. Levels of unesterified cholesterol were 2-fold greater than in fibroblasts cultured with LDL alone. Progesterone strongly blocked cholesteryl ester synthesis. When cellular uptake of LDL was monitored in the presence of 58035, a specific inhibitor of acyl-CoA:cholesterol acyltransferase, excess unesterified cholesterol was not stored in lysosomes. Discontinuation of LDL uptake in conjunction with progesterone washout markedly reversed the filipin-cholesterol staining of lysosomes. Reversal of the lysosomal cholesterol lipidosis was associated with a rapid burst of cholesteryl ester synthesis and a normalization of the cellular levels of free and esterified cholesterol. In contrast to normal cells, progesterone removal from Niemann-Pick C fibroblasts did not reverse the lysosomal cholesterol accumulation of these mutant cultures. The metabolic precursor of progesterone, pregnenolone, also induced extensive accumulation of cholesterol in lysosomes. Other steroids induced less vacuolar cholesterol accumulation in the following decreasing order: corticosterone and testosterone, promegestone, RU 486. The relative inhibition of cellular cholesterol esterification by the steroids paralleled their respective abilities to sequester cholesterol in lysosomes rather than their inhibition of acyl-CoA:cholesterol acyltransferase activity in cell-free extracts. The progesterone-related inhibition and restoration of lysosomal cholesterol trafficking is a useful experimental means of studying intracellular cholesterol transport. A particularly important feature of its utility is the facile reversibility of the steroid-induced block. The lysosomal cholesterol lipidosis established with a hydrophobic amine, U18666A, was not as readily reversed. C1 NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. VET ADM MED CTR,NEUROL SERV,NEWINGTON,CT 06111. FAC MED LYON SUD,BIOCHIM LAB,INSERM,U189,F-69921 OULLINS,FRANCE. OI Patterson, Marc/0000-0002-1116-126X NR 58 TC 143 Z9 143 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 23797 EP 23805 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900057 PM 1429719 ER PT J AU SINGH, K MUKHERJEE, AB DEVOUGE, MW MUKHERJEE, BB AF SINGH, K MUKHERJEE, AB DEVOUGE, MW MUKHERJEE, BB TI DIFFERENTIAL PROCESSING OF OSTEOPONTIN TRANSCRIPTS IN RAT KIDNEY-DERIVED AND OSTEOBLAST-DERIVED CELL-LINES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SECRETED PHOSPHOPROTEIN-I; TRANSFORMED MAMMALIAN-CELLS; PHYSIOLOGICAL-PROPERTIES; NONPHOSPHORYLATED FORMS; GROWTH-FACTORS; MESSENGER-RNA; BONE; EXPRESSION; PROTEINS; 2AR AB Using immunoprecipitation and tryptic peptide microsequencing we confirmed the identity of normal rat kidney (NRK) cell-secreted 69-kDa major phosphoprotein as osteopontin (OP). We then immunoselected a 1.4-kilobase pair (kb) OP cDNA from a lambdagt11 library prepared from Kirsten sarcoma virus-transformed NRK (KNRK) cellular mRNA, using rabbit anti-69-kDa OP serum. Sequence analysis of this cDNA revealed the presence of a 52-nucleotide-long insert in the 5'-noncoding region, which was absent in OP cDNA cloned from the cDNA library of ROS 17/2.8 rat osteosarcoma cells. The insert sequence is flanked by putative intron splice junctions and is located 15-nucleotide upstream of the translational initiation site. An insert-specific 30-mer oligonucleotide probe hybridized to a single 1.5-kb RNA species from both NRK and KNRK cells, but not from ROS 17/2.8 cells. However, Southern analysis showed the presence of this insert sequence in the genomic DNA of both NRK and ROS 17/2.8 cells. Furthermore, PCR amplification of the insert-containing region using genomic DNAs from both NRK and ROS 17/2.8 cells gave products of identical size and sequence. Since OP is a single copy gene, these data provide strong evidence for differential cell type-specific processing of OP transcripts. In addition, we demonstrate that, in contrast to most transformed cells, levels of OP expression are significantly reduced in KNRK cells as compared to NRK cells. C1 MCGILL UNIV,CTR HUMAN GENET,MONTREAL H3A 1B1,QUEBEC,CANADA. NICHHD,HUMAN GENET BRANCH,DEV GENET SECT,BETHESDA,MD 20892. RP SINGH, K (reprint author), MCGILL UNIV,DEPT BIOL,1205 DR PENFIELD AVE,MONTREAL H3A 1B1,QUEBEC,CANADA. NR 34 TC 38 Z9 40 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 23847 EP 23851 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900063 PM 1429723 ER PT J AU BRZESKA, H KULESZALIPKA, D KORN, ED AF BRZESKA, H KULESZALIPKA, D KORN, ED TI INHIBITION OF ACANTHAMOEBA MYOSIN-I HEAVY-CHAIN KINASE BY CA2+-CALMODULIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALMODULIN-BINDING PROTEIN; ACTIN-BINDING; BRUSH-BORDER; DICTYOSTELIUM-DISCOIDEUM; MG2+-ATPASE ACTIVITY; COFACTOR PROTEIN; PLASMA-MEMBRANE; 3RD ISOFORM; C SUBSTRATE; AMINO-ACID AB The actin-activated Mg2+-ATPase activity of Acanthamoeba myosins I depends on phosphorylation of their single heavy chains by myosin I heavy chain kinase. Kinase activity is enhanced >50-fold by autophosphorylation at multiple sites. The rate of kinase autophosphorylation is increased approximately 20-fold by acidic phospholipids independent of the presence of Ca2+ and diglycerides. We show in this paper that Ca2+-calmodulin inhibits phospholipid-stimulated autophosphorylation of myosin I heavy chain kinase and hence also inhibits the catalytic activity of unphosphorylated kinase in the presence of phospholipid. Ca2+-calmodulin does not inhibit kinase activity in the absence of phospholipid. Micromolar Ca2+-calmodulin also inhibits binding of myosin I heavy chain kinase to phospholipid vesicles and purified plasma membranes. Proteolytic removal of a 7-kDa NH2-terminal segment from the 97-kDa kinase prevents binding of both calmodulin and phospholipid; therefore, we propose that they bind to the same or overlapping sites. These data provide a mechanism by which Ca2+ could inhibit the actin-activated Mg2+-ATPase activity of the myosin I isozymes in vivo and thus regulate myosin I-dependent motile activities. RP BRZESKA, H (reprint author), NHLBI,CELL BIOL LAB,BETHESDA,MD 20892, USA. RI Korn, Edward/F-9929-2012 NR 70 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 23870 EP 23875 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900066 PM 1331103 ER PT J AU LINNEKIN, D EVANS, G MICHIEL, D FARRAR, WL AF LINNEKIN, D EVANS, G MICHIEL, D FARRAR, WL TI CHARACTERIZATION OF A 97-KDA PHOSPHOTYROSYLPROTEIN REGULATED BY MULTIPLE CYTOKINES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; RECEPTOR-BETA-CHAIN; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; CELL-LINE; ERYTHROPOIETIN RECEPTOR; INTERLEUKIN-2 RECEPTOR; GM-CSF; RAPID PHOSPHORYLATION; EXPRESSION CLONING AB We have examined the signal transduction pathways of a number of cytokines that interact with receptors that are members of the hematopoietin receptor superfamily. A 97-kDa protein was phosphorylated on tyrosine in response to stimulation of appropriate target cells with interleukin (IL)-2, IL-3, granulocyte-macrophage colony-stimulating factor (CSF), granulocyte-CSF, or erythropoietin. These data suggest that a 97-kDa phosphotyrosylprotein represents a point of convergence for signal transduction by a number of growth factor receptors that do not have homology with any known protein tyrosine kinase. To address the possibility that p97 may represent a tyrosine kinase involved in multiple signal transduction pathways, we tested the capacity of this protein to bind a tyrosine kinase substrate or ATP. Indeed, a 97-kDa phosphotyrosylprotein purified from IL-2-stimulated lymphoid cells as well as granulocyte-macrophage-CSF-stimulated myeloid cells bound to a polymer of glutamic acid and tyrosine which is a tyrosine kinase substrate. Further, a 97-kDa phosphotyrosylprotein present in both lineages also bound 8-azido-ATP. These data indicate that a 97-kDa phosphotyrosylprotein with properties consistent with those of a protein tyrosine kinase is involved in the signal transduction pathways of certain members of the newly identified hematopoietin receptor superfamily and may represent an early point of convergence in the stimulus-response coupling of multiple cytokine receptors. C1 NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, MOLEC IMMUNOREGULAT LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR,DYN CORP, PROGRAM RESOURCES INC, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, DYN CORP, PROGRAM RESOURCES INC, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74102] NR 36 TC 44 Z9 45 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 23993 EP 23998 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900084 PM 1385430 ER PT J AU RUI, H DJEU, JY EVANS, GA KELLY, PA FARRAR, WL AF RUI, H DJEU, JY EVANS, GA KELLY, PA FARRAR, WL TI PROLACTIN RECEPTOR TRIGGERING - EVIDENCE FOR RAPID TYROSINE KINASE ACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; GROWTH-HORMONE RECEPTOR; ERYTHROPOIETIN RECEPTOR; SIGNAL TRANSDUCTION; EXPRESSION CLONING; MOLECULAR-CLONING; PROTEIN-KINASE; LIGAND-BINDING; CYTOPLASMIC REGION; LYMPHOMA-CELLS AB The mechanism of action of prolactin (PRL) has remained obscure despite the unveiling of the primary structure of PRL receptors. The present study demonstrates rapid PRL receptor-mediated tyrosine phosphorylation of at least three cellular proteins, designated p120, p97, and p40, in a rat T-lymphoma (Nb2-11C) as revealed by antiphosphotyrosine immunoblotting. One of the phosphotyrosyl proteins, p120, co-purified with activated PRL receptor complexes obtained using either anti-ligand or anti-receptor antibodies. Furthermore, in vitro incubation of affinity-purified PRL receptor complexes from PRL-stimulated cells with ATP in the presence of a tyrosine phosphatase inhibitor, resulted in a 10-15-fold increase in the phosphotyrosine content of p120, as revealed by antiphosphotyrosine immunoblotting. Parallel experiments utilizing [gamma-P-32]ATP confirmed a rapid and time-dependent incorporation of phosphate into p120 in the same affinity-purified PRL receptor complexes. These data provide strong evidence for the involvement of a tyrosine kinase in PRL signal transduction and suggest the presence of a tyrosine kinase within the activated PRL receptor complex. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. UNIV S FLORIDA,H LEE MOFFITT CANC INST & RES CTR,TAMPA,FL 33612. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. FAC MED NECKER ENFANTS MALAD,INSERM,U344,UNITE ENDOCRINOL MOLEC,F-75730 PARIS 15,FRANCE. RI Kelly, Paul/A-7951-2008 FU FIC NIH HHS [5FO5 TWO4300-02]; NCI NIH HHS [N01-CO-74102] NR 49 TC 117 Z9 119 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 24076 EP 24081 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900097 PM 1385436 ER PT J AU MISHIMA, K PRICE, SR NIGHTINGALE, MS KOUSVELARI, E MOSS, J VAUGHAN, M AF MISHIMA, K PRICE, SR NIGHTINGALE, MS KOUSVELARI, E MOSS, J VAUGHAN, M TI REGULATION OF ADP-RIBOSYLATION FACTOR (ARF) EXPRESSION - CROSS-SPECIES CONSERVATION OF THE DEVELOPMENTAL AND TISSUE-SPECIFIC ALTERNATIVE POLYADENYLATION OF ARF-4 MESSENGER-RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; NUCLEOTIDE-BINDING-PROTEINS; AMINO-ACID SEQUENCE; CHOLERA-TOXIN; MOLECULAR-CLONING; HUMAN TESTIS; ADENYLATE-CYCLASE; CDNA STRUCTURE; CODING REGION; BOVINE BRAIN AB ADP-ribosylation factors (ARFs), approximately 20-kDa guanine nucleotide-binding proteins, are involved in protein trafficking and enhance cholera toxin ADP-ribosyltransferase activity. Expression of six ARF genes was examined in mammalian tissues; only ARF 4 mRNA was detected in rat testis in forms considerably shorter than those in other tissues. Testis-specific expression of short forms of ARF 4 mRNA was observed in several mammalian species. On Northern analysis of the developmental expression of rat ARF 4 mRNA, appearance of the shorter species was consistent with its involvement in a late stage of spermatogenesis. Sequences of products of rapid amplification of cDNA ends (RACE-polymerase chain reaction) of rat ARF 4 mRNA revealed that different mRNAs resulted from the use of three polyadenylation signals, one AUUAAA and two AAUAAA. Sequences of 3'-untranslated regions of rat and human ARF 4 mRNA were very similar with identical polyadenylation signals at similar positions. Of the ARF 4 mRNAs identified by RACE-PCR, with sizes of 1.1, 1.3, and 1.8 kb, the 1.1-kb mRNA was predominant in adult testis. By in situ hybridization, the 1.1-kb mRNA was identified primarily in mature sperm, consistent with the developmental studies. Shorter mRNAs, thought to be more stable, may compensate for cessation of transcription at late stages of spermatogenesis. C1 NIDR, PATIENT CARE BRANCH, BETHESDA, MD 20892 USA. RP MISHIMA, K (reprint author), NHLBI, CELLULAR METAB LAB, BETHESDA, MD 20892 USA. NR 59 TC 24 Z9 25 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 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1992 VL 267 IS 33 BP 24109 EP 24116 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ239 UT WOS:A1992JZ23900102 PM 1358888 ER EF