FN Thomson Reuters Web of Science™ VR 1.0 PT J AU TAKAHAMA, Y SHORES, EW SINGER, A AF TAKAHAMA, Y SHORES, EW SINGER, A TI NEGATIVE SELECTION OF PRECURSOR THYMOCYTES BEFORE THEIR DIFFERENTIATION INTO CD4+CD8+ CELLS SO SCIENCE LA English DT Article ID RECEPTOR TRANSGENIC MICE; BETA-T-CELL; IMMATURE THYMOCYTES; MONOCLONAL-ANTIBODY; CLONAL ELIMINATION; CD4+8+ THYMOCYTES; ANTIGEN RECEPTOR; INVIVO; INTERMEDIATE; GENERATION AB Thymic selection of the developing T cell repertoire is thought to occur at the CD4+CD8+ stage of differentiation and to be determined by the specificity of the T cell receptors (TCRs) that CD4+CD8+ thymocytes express. However, TCR signals can inhibit the differentiation of precursor thymocytes into CD4+CDB+ cells, which suggests that selection might occur earlier than thought. Indeed, in a negatively selecting male thymus, CD4-CD8(lo) precursor thymocytes that express a transgenic TCR to male antigen are developmentally arrested as a consequence of antigen encounter and fail to become CD4+CD8+. Thus, negative selection can occur before the CD4+CD8+ stage of differentiation. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 31 TC 104 Z9 105 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 OCT 23 PY 1992 VL 258 IS 5082 BP 653 EP 656 DI 10.1126/science.1357752 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JU745 UT WOS:A1992JU74500058 PM 1357752 ER PT J AU ZIEGELSTEIN, RC CHENG, L CAPOGROSSI, MC AF ZIEGELSTEIN, RC CHENG, L CAPOGROSSI, MC TI FLOW-DEPENDENT CYTOSOLIC ACIDIFICATION OF VASCULAR ENDOTHELIAL-CELLS SO SCIENCE LA English DT Article ID DEPOLARIZATION-INDUCED ALKALINIZATION; INTRACELLULAR PH REGULATION; LYMPHOCYTE VOLUME REGULATION; ACTIVATING FACTOR PRODUCTION; ESTER INDUCED ACTIVATION; BOVINE AORTIC-CELLS; CHICK HEART-CELLS; NA+-H+ EXCHANGE; SHEAR-STRESS; PROXIMAL TUBULES AB Hemodynamic shear stress affects endothelial cell structure and function, but little is known about the signal transduction mechanisms involved in these processes. The effect of laminar shear stress on cytosolic pH (pH(i)) was examined in rat aortic endothelial cells cultured in glass capillary tubes. Shear stress forces led to a rapid decrease in pH(i) (maximal effect 0.09 pH unit at 13.4 dynes per square centimeter). Removal of specific ions or addition of exchange inhibitors suggests that in vascular endothelial cells shear stress forces activate both an alkali extruder, sodium ion-independent chloride-bicarbonate ion exchange, and an acid extruder, sodium-hydrogen ion exchange; the net effect in physiologic buffer with the bicarbonate ion is a decrease in pH(i). C1 NIA,FAMILY PRACTICE RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DIV CARDIOL,BALTIMORE,MD 21205. NR 34 TC 103 Z9 104 U1 1 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 OCT 23 PY 1992 VL 258 IS 5082 BP 656 EP 659 DI 10.1126/science.1329207 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JU745 UT WOS:A1992JU74500059 PM 1329207 ER PT J AU COSSON, P BONIFACINO, JS AF COSSON, P BONIFACINO, JS TI ROLE OF TRANSMEMBRANE DOMAIN INTERACTIONS IN THE ASSEMBLY OF CLASS-II MHC MOLECULES SO SCIENCE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MEMBRANE-PROTEINS; RECEPTOR; EXPRESSION; PRODUCTS; DISTINCT; COMMON; GENES; MODEL; CLONE AB Evidence is presented that suggests a role for transmembrane domain interactions in the assembly of class II major histocompatibility complex (MHC) molecules. Mutations in the transmembrane domains of the class II MHC alpha or beta chains resulted in proteins that did not generate complexes recognized by conformation-dependent antibodies and that were largely retained in the endoplasmic reticulum. Insertion of the alpha and beta transmembrane domains into other proteins allowed the chimeric proteins to assemble, suggesting a direct interaction of the alpha and beta transmembrane domains. The interactions were mediated by a structural motif involving several glycine residues on the same face of a putative alpha helix. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 33 TC 173 Z9 181 U1 0 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 23 PY 1992 VL 258 IS 5082 BP 659 EP 662 DI 10.1126/science.1329208 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JU745 UT WOS:A1992JU74500060 PM 1329208 ER PT J AU UHL, GR AF UHL, GR TI ELUCIDATING NEUROTENSIN RECEPTOR CDNAS AND THEIR DISTRIBUTION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID PROTEIN-COUPLED RECEPTOR; COMPLETE NUCLEOTIDE-SEQUENCE; BLASTOMA CLONE N1E-115; CENTRAL NERVOUS-SYSTEM; TRANSFECTED COS CELLS; CYCLIC-GMP FORMATION; RAT-BRAIN; XENOPUS OOCYTES; BINDING; EXPRESSION C1 NIDA ARC,MOLEC NEUROBIOL LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. RP UHL, GR (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,POB 5180,BALTIMORE,MD 21205, USA. NR 32 TC 3 Z9 3 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD OCT 22 PY 1992 VL 668 BP 101 EP 108 DI 10.1111/j.1749-6632.1992.tb27342.x PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KD116 UT WOS:A1992KD11600010 PM 1334383 ER PT J AU FUJIMURA, T RIBAS, JC MAKHOV, AM WICKNER, RB AF FUJIMURA, T RIBAS, JC MAKHOV, AM WICKNER, RB TI POL OF GAG-POL FUSION PROTEIN REQUIRED FOR ENCAPSIDATION OF VIRAL-RNA OF YEAST L-A-VIRUS SO NATURE LA English DT Article ID HEPATITIS-B VIRUS; SACCHAROMYCES-CEREVISIAE; GENOMIC RNA; INVITRO; REPLICATION; POLYMERASE; TRANSCRIPTION; MATURATION; PARTICLES AB DOUBLE-STRANDED RNA viruses have an RNA-dependent RNA polymerase activity associated with the viral particles which is indispensable for their replication cycle. Using the yeast L-A double-stranded RNA virus we have investigated the mechanism by which the virus encapsidates its genomic RNA and RNA polymerase. The L-A gag gene encodes the principal viral coat protein and the overlapping pol gene is expressed as a gag-pol fusion protein which is formed by a -1 ribosomal frameshift1-3. Here we show that Gag alone is sufficient for virus particle formation, but that it fails to package the viral single-stranded RNA genome. Encapsidation of the viral RNA requires only a part of the Pol region (the N-terminal quarter), which is presumably distinct from the RNA polymerase domain. Given that the Pol region has single-stranded RNA-binding activity, these results are consistent with our LA virus encapsidation model1: the Pol region of the fusion protein binds specifically to the viral genome (+) strand, and the N-terminal gag-encoded region primes polymerization of Gag to form the capsid, thus ensuring the packaging of both the viral genome and the RNA polymerase. C1 NIDDKD,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. RP FUJIMURA, T (reprint author), UNIV SALAMANCA,CSIC,DEPT MICROBIOL & GENET,INST MICROBIOL BIOQUIM,E-37071 SALAMANCA,SPAIN. RI Fujimura, Tsutomu/K-5807-2014; Ribas, Juan/C-9864-2015 OI Fujimura, Tsutomu/0000-0002-9457-6769; Ribas, Juan/0000-0001-6430-0895 NR 25 TC 61 Z9 62 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 22 PY 1992 VL 359 IS 6397 BP 746 EP 749 DI 10.1038/359746a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JU650 UT WOS:A1992JU65000062 PM 1436038 ER PT J AU WILCOX, AJ AF WILCOX, AJ TI INFANT-MORTALITY AMONG BLACKS AND WHITES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID BIRTH-WEIGHT; PERINATAL-MORTALITY RP WILCOX, AJ (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 9 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 OCT 22 PY 1992 VL 327 IS 17 BP 1243 EP 1243 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JU393 UT WOS:A1992JU39300026 PM 1406810 ER PT J AU DE LUCA, LM SLY, L JONES, CS CHEN, LC AF DE LUCA, LM SLY, L JONES, CS CHEN, LC TI DIETARY RETINOIDS ARE ESSENTIAL FOR SKIN PAPILLOMA FORMATION INDUCED BY EITHER THE 2-STAGE OR THE COMPLETE TUMORIGENESIS MODEL IN FEMALE SENCAR MICE SO CANCER LETTERS LA English DT Article DE RETINOIC ACID; RETINOIDS; SKIN TUMORIGENESIS; 2-STAGE CARCINOGENESIS; COMPLETE CARCINOGENESIS ID VITAMIN-A ACID; EPITHELIAL TUMORS; MOUSE SKIN; PROMOTION; INHIBITION; CARCINOGENESIS; ANALOG; SUSCEPTIBILITY; PROPHYLAXIS; PALMITATE AB Our previous work has shown that dietary retinoic acid (RA) is necessary for skin tumor formation induced by the two-stage protocol with the initiator 7,12-dimethylbenz[a]anthracene (DMBA) and the promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) (De Luca et al., Cancer Res., 36 (1976) 2334 - 2339). Here we report that retinoids are required for tumorigenesis by the two-stage as well as by the complete tumorigenesis protocol. Mice were treated with a single dose of DMBA (20 Ag), followed by 20 applications of TPA (2 mug), or by 20 applications of DMBA (25 mug for 2 weeks and 51 mug thereafter). Regardless of the tumor induction protocol, tumor formation was inhibited by vitamin A-deficiency, while RA (3 mug/g of diet) or retinyl palmitate (RP, 6 mug/g) supplementation permitted the appearance of tumors. In addition, in comparison to the purified diets and regardless of their RA levels, the non-purified Purina chow diet enhanced tumor yield especially in the two-stage tumorigenesis protocol. This effect was less striking in mice with tumors induced by the complete tumorigenesis protocol. In summary, dietary retinoids are essential for skin tumor formation induced either by the two-stage or the complete tumorigenesis protocol. C1 BIOCON, ROCKVILLE, MD USA. RP DE LUCA, LM (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NR 26 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 21 PY 1992 VL 66 IS 3 BP 233 EP 239 DI 10.1016/0304-3835(92)90252-Q PG 7 WC Oncology SC Oncology GA JX330 UT WOS:A1992JX33000008 PM 1451104 ER PT J AU CHAUHAN, SS GOTTESMAN, MM AF CHAUHAN, SS GOTTESMAN, MM TI CONSTRUCTION OF A NEW UNIVERSAL VECTOR FOR INSERTIONAL MUTAGENESIS BY HOMOLOGOUS RECOMBINATION SO GENE LA English DT Note DE RECOMBINANT DNA; ELECTROPORATION; EMBRYONAL STEM CELLS; THYMIDINE KINASE; NEOMYCIN RESISTANCE ID EMBRYONIC STEM-CELLS; TARGETED DISRUPTION; TRANSGENIC MICE; GENE; PROTOONCOGENE; MUTATION; LINE; DNA AB We describe here the construction of a vector (pSSC-9) which can be used for the insertional mutagenesis of any gene for which genomic sequences have been cloned. This vector contains a neomycin-resistance-encoding gene (neo(R)) which is driven by a modified thymidine kinase (tk) promoter for positive selection. Flanking neo(R) are two tk genes driven by their own promoters for negative selection of nonhomologous insertions. The neo(R) and tk cassettes are separated by four unique cloning sites on the right-hand side of the neo(R) cassette and three unique sites on the left-hand side. The vector also includes two SfiI sites, one on each side of the tk cassettes, for the excision of the cloned genomic DNA fragments along with the selectable markers. Electroporation of pSSC-9 into mouse embryonic stem (ES) cells and cultured diploid mouse adrenal Y-1 cells conferred resistance to G418 and sensitivity to ganciclovir in both cell lines. These results illustrate the expression of the positive and negative selectable markers in two different cell lines and thus suggest that the vector could be used in ES cells, as well as in cultured somatic cells. C1 NCI,CELL BIOL LAB,BLDG 37-1B22,BETHESDA,MD 20892. NR 17 TC 16 Z9 17 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 OCT 21 PY 1992 VL 120 IS 2 BP 281 EP 286 DI 10.1016/0378-1119(92)90106-Y PG 6 WC Genetics & Heredity SC Genetics & Heredity GA JU621 UT WOS:A1992JU62100021 PM 1327975 ER PT J AU ZHENG, W BLOT, WJ SHU, XO DIAMOND, EL GAO, YT JI, BT FRAUMENI, JF AF ZHENG, W BLOT, WJ SHU, XO DIAMOND, EL GAO, YT JI, BT FRAUMENI, JF TI A POPULATION-BASED CASE-CONTROL STUDY OF CANCERS OF THE NASAL CAVITY AND PARANASAL SINUSES IN SHANGHAI SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MAXILLARY SINUS; EPIDEMIOLOGY; WOODWORKING; EXPOSURE; DIET AB A population-based case-control study of cancer of the nasal cavity and sinuses, involving interviews of 60 incident cases and 414 controls, was conducted in Shanghai. Cigarette smoking was associated with a mild elevation in risk of squamous-cell carcinoma but not cancers of other cell types. Occupational exposures to wood and silica dusts and to petroleum products, and the use of wood and straw as cooking fuel, were linked to moderate increases in risk, while 4-fold or greater increases were associated with a history of chronic nasal diseases, including those occurring 10 or more years prior to cancer diagnosis. Dietary analyses revealed a significant protective effect of consumption of allium vegetables, oranges and tangerines, with a 50% reduced risk of nasal cancer among individuals in the highest intake group of these foods. Consumption of salt-preserved vegetables, meat and fish was associated with a significantly increased risk of nasal cancer in a dose-response fashion, with a 5-fold excess observed for the heaviest intake of these salted foods. These findings suggest that dietary factors may contribute to the development of nasal cancer. C1 SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP ZHENG, W (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 431,BETHESDA,MD 20892, USA. NR 22 TC 38 Z9 39 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 21 PY 1992 VL 52 IS 4 BP 557 EP 561 DI 10.1002/ijc.2910520410 PG 5 WC Oncology SC Oncology GA JV131 UT WOS:A1992JV13100009 PM 1399136 ER PT J AU MCLAUGHLIN, JK GAO, YT GAO, RN ZHENG, W JI, BT BLOT, WJ FRAUMENI, JF AF MCLAUGHLIN, JK GAO, YT GAO, RN ZHENG, W JI, BT BLOT, WJ FRAUMENI, JF TI RISK-FACTORS FOR RENAL-CELL CANCER IN SHANGHAI, CHINA SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CARCINOMA AB A population-based case-control study of 154 histologically verified renal-cell cancer patients and 157 controls was performed in Shanghai, China. an area with low rates for this tumor. Elevated risks were observed for cigarette smoking (odds ratio (OR) = 2.3; 95% confidence interval (CI):1.1 to 4.9) and for increasing categories of body weight and meat consumption, while reduced risks were seen for increasing categories of fruit and vegetable intake. An increased risk was also observed for regular use of phenacetin-containing analgesics (OR = 2.3; 95% CI:0.7 to 7.0), These findings are consistent with earlier studies in Western countries, and indicate that many of the same etiologic factors for renal-cell cancer operate in low- and high-risk societies. C1 SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. RP MCLAUGHLIN, JK (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN-415,BETHESDA,MD 20892, USA. NR 23 TC 116 Z9 119 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 21 PY 1992 VL 52 IS 4 BP 562 EP 565 DI 10.1002/ijc.2910520411 PG 4 WC Oncology SC Oncology GA JV131 UT WOS:A1992JV13100010 PM 1399137 ER PT J AU VANDENBRULE, FA ENGEL, J STETLERSTEVENSON, WG LIU, FT SOBEL, ME CASTRONOVO, V AF VANDENBRULE, FA ENGEL, J STETLERSTEVENSON, WG LIU, FT SOBEL, ME CASTRONOVO, V TI GENES INVOLVED IN TUMOR INVASION AND METASTASIS ARE DIFFERENTIALLY MODULATED BY ESTRADIOL AND PROGESTIN IN HUMAN BREAST-CANCER CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LAMININ RECEPTOR; TISSUE INHIBITOR; CARCINOMA-CELLS; BINDING PROTEIN; IV COLLAGENASE; MESSENGER-RNA; EXPRESSION; GROWTH; LINES; INVASIVENESS AB Invasion of basement membranes by cancer cells is a critical step in metastasis, which requires the coordinated expression of specific genes such as laminin receptors and metalloproteinases. Estradiol and progesterone modulate the clinical progression of steroid-sensitive breast cancers; however little is known about the molecular regulation of the invasive phenotype by these hormones. We therefore examined the effects of 10 nM estradiol and/or 10 nM progestin R5020 on the expression of 2 non-integrin laminin binding proteins, the 67-kDa laminin receptor (67LR) and HLBP31 as well as the 72-kDa type-IV collagenase (MMP-2) and its inhibitor, TIMP-2, in steroid-receptor-positive (T47D and MCF-7) and -negative (MDA-MB 231) human breast-cancer cells. The relative steady-state level of 67LR mRNA was increased 2- to 3-fold by estradiol in both MCF-7 (p < 0.001) and T47D (p < 0.001) cells, also by R5020, alone or in combination with estradiol, in T47D cells (p < 0.001) and to a much less extent in MCF-7 cells. HLBP31 mRNA and protein levels were increased 2- to 3-fold (p < 0.001) by R5020 alone or in combination with estradiol, but not by estradiol alone. None of the steroid treatments affected the expression or activity of MMP-2. Interestingly, however, TIMP-2 mRNA levels and protein expression in MCF-7 and T47D cells were 50% down-regulated (p < 0.001) by treatment with R5020 or R5020 plus estradiol, but not by treatment with estradiol alone. None of these genes were modulated in steroid-independent MDA-MB231 cells. The data suggest that estradiol and progesterone might act as coordinators regulating specific genes in the steroid-sensitive breast-cancer cell, leading to the acquisition of the metastatic hen C1 SCRIPPS CLIN & RES FDN,LA JOLLA,CA 92037. RP VANDENBRULE, FA (reprint author), NCI,PATHOL LAB,TUMOR INVAS & METASTASIS SECT,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 33 TC 49 Z9 49 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 21 PY 1992 VL 52 IS 4 BP 653 EP 657 DI 10.1002/ijc.2910520426 PG 5 WC Oncology SC Oncology GA JV131 UT WOS:A1992JV13100025 PM 1399148 ER PT J AU COTE, TR BIGGAR, RJ DANNENBERG, AL AF COTE, TR BIGGAR, RJ DANNENBERG, AL TI RISK OF SUICIDE AMONG PERSONS WITH AIDS - A NATIONAL ASSESSMENT SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Note ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IOWA RECORD-LINKAGE; MORTALITY; DISORDERS AB Objective.-We sought to describe the rate, risk, trends, methods, and distribution of suicide among persons with the acquired immunodeficiency syndrome (AIDS) in the United States. Design.-We used National Center for Health Statistics multiple-cause mortality data from 1987 through 1989 to identify suicides among persons with AIDS (PWAs) and public-access AIDS surveillance data to determine person-years of observation of PWAs. Patients.-Residents of the United States with death certificates indicating suicide. Main Outcome Measure.-Death certificates indicating both AIDS and suicide. Results.-In 1987 through 1989, a total of 165 suicides among PWAs occurred in 45 states and the District of Columbia. All but one case were male. Among males the rate was 165 per 100 000 person-years of observation, 7.4-fold higher than among demographically similar men in the general population. Self-poisoning with drugs was both the most common method (35%) and the method with the highest standardized mortality ratio (35). Suicide risk for PWAs decreased significantly (P<.05) from 1987 to 1989. Conclusion.-Persons with AIDS have an increased risk of suicide, and assessment of such risk should be a standard practice in their care. These assessments should be carefully considered when potentially lethal medications are prescribed. The declining trend in suicide rates between 1987 and 1989 is encouraging; possible causes include emerging therapies for human immunodeficiency virus/AIDS, better psychiatric care for these patients, and lessened social stigma against PWAs. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR INJURY PREVENT,BALTIMORE,MD 21218. RP COTE, TR (reprint author), NCI,VIRAL EPIDEMIOL SECT,6130 EXECUT PLAZA,EPN-434,ROCKVILLE,MD 20852, USA. NR 18 TC 73 Z9 73 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 21 PY 1992 VL 268 IS 15 BP 2066 EP 2068 DI 10.1001/jama.268.15.2066 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA JT520 UT WOS:A1992JT52000031 PM 1404744 ER PT J AU PLOTZ, PH AF PLOTZ, PH TI NOT MYOSITIS - A SERIES OF CHANCE ENCOUNTERS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DEFICIENCY; MYOPATHY RP PLOTZ, PH (reprint author), NIAMSD,ARTHRIT RHEUMATISM BRANCH,CONNECT TISSUE DIS SECT,CTR CLIN 9N244,BETHESDA,MD 20892, USA. NR 12 TC 9 Z9 11 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 OCT 21 PY 1992 VL 268 IS 15 BP 2074 EP 2077 DI 10.1001/jama.268.15.2074 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA JT520 UT WOS:A1992JT52000033 PM 1404746 ER PT J AU STENGER, DA GEORGER, JH DULCEY, CS HICKMAN, JJ RUDOLPH, AS NIELSEN, TB MCCORT, SM CALVERT, JM AF STENGER, DA GEORGER, JH DULCEY, CS HICKMAN, JJ RUDOLPH, AS NIELSEN, TB MCCORT, SM CALVERT, JM TI COPLANAR MOLECULAR ASSEMBLIES OF AMINOALKYLSILANE AND PERFLUORINATED ALKYLSILANE - CHARACTERIZATION AND GEOMETRIC DEFINITION OF MAMMALIAN-CELL ADHESION AND GROWTH SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HIPPOCAMPAL-NEURONS; MONOLAYERS; SURFACES; GOLD; SILICON; ALKANETHIOLS; SPECTROSCOPY; ELECTRODES; ADSORPTION; PROTEINS AB The photochemistry of organosilanes was used to (1) create mixed monolayers having continuously adjustable surface free energies and (2) affect high resolution adhesion and spatial orientation of biological cells on silica substrates. Monolayers were formed from two materials, an aminoalkylsilane, NH2(CH2)2NH(CH2)3Si(OCH3)3 (EDA), and a perfluorinated alkylsilane, CF3(CF2)5(CH2)2Si(CH3)2Cl (13F), and were characterized by ellipsometry and water contact angle measurements. Deep UV (193 nm) radiation was used to induce photochemical changes in the cell-adhesive EDA monolayers. X-ray photoelectron spectroscopy indicated that the amine groups of EDA were removed by the exposure, leaving only Si-OH or alkyl fragments having less-than-or-equal-to 3 carbons. The exposed substrates were then reacted with 13F to form mixed monolayers or hydrophobic monolayers that inhibited cell adhesion in the irradiated regions. The degree of 13F reactivity with EDA in the unirradiated regions was observed to be solvent-dependent, suggesting that conformational states of the surface amine groups lead to a reduction in their accessibility. The selective photochemistry was exploited to produce high resolution molecular patterns, defined using patterned irradiation, that were mapped with scanning Auger electron spectroscopy. The patterns were used to spatially control the adhesion and direct the outgrowth of rat hippocampal neurons and porcine aortic endothelial cells in vitro. Patterns of controlled geometry may provide new approaches to the study of surface-directed growth, intercellular communication, and organogenesis or be used to control the alignment of individual cells with transducer elements in biosensors and implants. C1 GEOCENTERS INC,FT WASHINGTON,MD 20744. SCI APPLICAT INT CORP,MCLEAN,VA 22102. NIAAA,ROCKVILLE,MD 20852. USN,MED RES INST,BETHESDA,MD 20889. RP STENGER, DA (reprint author), USN,RES LAB,WASHINGTON,DC 20375, USA. NR 40 TC 281 Z9 283 U1 0 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 21 PY 1992 VL 114 IS 22 BP 8435 EP 8442 DI 10.1021/ja00048a013 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA JV028 UT WOS:A1992JV02800013 ER PT J AU MARINI, AM FRIDMAN, R KANEMOTO, T MARTIN, GR GUO, Y PASSANITI, A AF MARINI, AM FRIDMAN, R KANEMOTO, T MARTIN, GR GUO, Y PASSANITI, A TI THE NEUROTOXIN 1-METHYL-4-PHENYLPYRIDINIUM - A SELECTIVE CYTOSTATIC AGENT IN SMALL-CELL LUNG-CANCER CELL-LINES WITH NEUROENDOCRINE PROPERTIES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; DOPAMINERGIC-NEURONS; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; MESENCEPHALON; DESTRUCTION; MOUSE AB Background: Small-cell lung cancer (SCLC) is a common malignancy that is usually fatal, since it metastasizes and recurs even after aggressive chemotherapy. While the cellular origin of this cancer is not well established, the cells of certain tumors exhibit neuroendocrine markers, including L-dopa decarboxylase. Purpose: We designed in vitro and in vivo studies to investigate whether the neuroendocrine features in classic SCLC cell lines were sufficient to make them sensitive to 1-methyl-4-phenylpyridinium (MPP+), a known neurotoxin that destroys nigrostriatal dopaminergic neurons. Methods: Both classic SCLC cell lines (NCI-H345, NCI-H510, NCI-H187, and NCI-H146) and variant SCLC cell lines (NCI-H417, NCI-H82, NCI-H446, and NCI-H524) were exposed to MPP+ (0-512 muM) for 3 days. Inhibition of DNA synthesis was determined by [H-3]thymidine incorporation assays. In a related experiment, MPP+ was removed from the classic cell line culture, and the incorporation of [H-3]thymidine was determined. In the in vivo study, male athymic nude mice received subcutaneous injections of 0.5 mL tumor cells with matrigel for 10 days to enhance tumor growth, followed by MPP+ at doses of 100-400 mug/d given intraperitoneally for 2 days. Results: All four classic SCLC cell lines showed great sensitivity to MPP+, with detachment from laminin substrates and inhibition of DNA synthesis. MPP+ interfered with [H-3]thymidine incorporation and, thus, with DNA synthesis in classic SCLC cell lines at low doses (median +/- SD, 12 +/- 4 muM), whereas much higher doses (median, >512 muM) were required to inhibit [H-3]thymidine incorporation in the variant lines. Treated cells excluded trypan blue dye, showing that inhibition of DNA synthesis was not due to cytotoxicity, and the cells incorporated [H-3]thymidine when MPP+ was removed from the culture medium, demonstrating that the inhibition was reversible. MPP+ inhibited the growth of the classic NCI-H187 and variant NCI-H417 cell lines implanted in nude mice. Conclusions: These results suggest that MPP+ differentially interferes with DNA synthesis in SCLC cell lines in vitro, the selective inhibitory effect on classic cell lines suggests that the neuroendocrine properties expressed by classic SCLC cells may be responsible for the differential effect. Implications: MPP+ exerts a cytostatic effect on these cell lines, and the differential sensitivity observed in vitro is maintained in vivo, suggesting that MPP+ or other pyridinium compounds may be of therapeutic value in SCLC. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NIA,GERONTOL RES CTR,BETHESDA,MD 20892. RP MARINI, AM (reprint author), NIMH,ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,CLIN NEUROSCI BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 12 TC 3 Z9 3 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 OCT 21 PY 1992 VL 84 IS 20 BP 1582 EP 1587 DI 10.1093/jnci/84.20.1582 PG 6 WC Oncology SC Oncology GA JV381 UT WOS:A1992JV38100011 PM 1328660 ER PT J AU SCOW, RO BLANCHETTEMACKIE, EJ AF SCOW, RO BLANCHETTEMACKIE, EJ TI ENDOTHELIUM, THE DYNAMIC INTERFACE IN CARDIAC LIPID TRANSPORT SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE FATTY ACID TRANSPORT; MONOACYLGLYCEROL TRANSPORT; LIPOPROTEIN LIPASE; INSULIN; LIPOLYSIS; CELL MEMBRANES; PLASMA TRIACYLGLYCEROL ID BROWN ADIPOSE-TISSUE; LIPOPROTEIN-LIPASE; FATTY-ACIDS; CAPILLARY ENDOTHELIUM; HEART-MUSCLE; YOUNG-RATS; ELECTRON-MICROSCOPE; BINDING PROTEINS; SKELETAL-MUSCLE; FREEZE-FRACTURE AB Vascular endothelium is the dynamic interface in transport of lipid from blood to myocytes in heart and arteries. The luminal surface of endothelium is the site of action of lipoprotein lipase on chylomicrons and VLDL and the site of uptake of fatty acids from albumin. Fatty acids and monoacylglycerols are transported from the lumen in an interfacial continuum of endothelial and myocyte membranes. Lipoprotein lipase is transferred from myocytes to the vascular lumen, and is anchored there, by proteoheparan sulfate in cell membranes. Insulin, needed for synthesis of lipoprotein lipase and esterfication of fatty acids, is captured from the blood stream and delivered to myocytes by endothelial insulin receptors. Fatty acids, monoacylglycerols, lipoprotein lipase and insulin are transported along the same route, but by different mechanisms. The route involves the plasma membrane of endothelium and myocytes, the membrane lining transendothelial channels, and intercellular contacts. RP SCOW, RO (reprint author), NIDDKD,ENDOCRINOL SECT,CELLULAR & DEV BIOL LAB,BLDG 6,ROOM 137,BETHESDA,MD 20892, USA. NR 50 TC 16 Z9 16 U1 0 U2 1 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 OCT 21 PY 1992 VL 116 IS 1-2 BP 181 EP 191 DI 10.1007/BF01270586 PG 11 WC Cell Biology SC Cell Biology GA JZ206 UT WOS:A1992JZ20600026 PM 1480147 ER PT J AU SCHMITT, JM GANDJBAKHCHE, AH BONNER, RF AF SCHMITT, JM GANDJBAKHCHE, AH BONNER, RF TI USE OF POLARIZED-LIGHT TO DISCRIMINATE SHORT-PATH PHOTONS IN A MULTIPLY SCATTERING MEDIUM SO APPLIED OPTICS LA English DT Article DE POLARIZATION; IMAGING; MULTIPLE SCATTERING ID DIFFUSING-WAVE SPECTROSCOPY; PULSE-PROPAGATION; PICOSECOND PULSE; TIME; TISSUES; DEPOLARIZATION; BACKSCATTERING AB We describe a method for discriminating short- and long-path photons transmitted through a multiply scattering medium that is based on the relationship between the polarization states of the incident and forward-scattered light. Results of Monte Carlo simulations and experiments show that if the scattering anisotropy of the scatterers is sufficiently small, absorbing barriers embedded in optically dense suspensions of polystyrene spheres can be resolved with good contrast by selectively detecting a component of the scattered-light intensity that has preserved its incident circular polarization state. The principles of operation of a polarization-modulation system capable of measuring small polarization fractions are explained. Using this system we were able to measure polarized light in a depolarized background over 1000 times as large. C1 NIH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. RP NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 24 TC 225 Z9 231 U1 3 U2 16 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD OCT 20 PY 1992 VL 31 IS 30 BP 6535 EP 6546 PG 12 WC Optics SC Optics GA JR914 UT WOS:A1992JR91400023 PM 20733872 ER PT J AU JONES, CR LUBET, RA AF JONES, CR LUBET, RA TI INDUCTION OF A PLEIOTROPIC RESPONSE BY PHENOBARBITAL AND RELATED-COMPOUNDS - RESPONSE IN VARIOUS INBRED STRAINS OF RATS, RESPONSE IN VARIOUS SPECIES AND THE INDUCTION OF ALDEHYDE DEHYDROGENASE IN COPENHAGEN RATS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID ARYL-HYDROCARBON HYDROXYLASE; LIVER MICROSOMAL CYTOCHROME-P-450; GLUTATHIONE S-TRANSFERASES; MESSENGER-RNAS; EPOXIDE HYDROLASE; IMMUNOCHEMICAL QUANTITATION; TESTOSTERONE HYDROXYLATION; SEQUENCE; MOUSE; GENE AB The ability of phenobarbital (PB) to induce a "pleiotropic response" which includes both cytochromes P450 (CYP) as well as other drug-metabolizing enzymes was investigated in mice, rabbits. hamsters, and various inbred strains of rats. PB induced similar drug-metabolizing enzymes (CYP2B, CYP3A, and epoxide hydrolase) in rats, mice, rabbits and hamsters. PB and two structural analogues (ethylphenylhydantoin and barbital) induced a variety of drug-metabolizing enzymes (CYP2B, CYP3A, CYP2A, epoxide hydrolase) in a series of inbred strains of rats. In contrast, levels of aldehyde dehydrogenase (ALDH) (propionaldehyde, NAD+) which were expressed constitutively in all strains of rats were induced by PB in only two of the eight strains (ACI, Copenhagen). Further investigations of ALDH induction by structurally diverse compounds in Copenhagen rats demonstrated a strong correlation between the induction of ALDH and other elements of the pleiotropic response (CYP2B, CYP3A, epoxide hydrolase). These results imply that induction of ALDH (propionaldehyde, NAD+) is associated with the PB pleiotropic response in Copenhagen rats. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702. PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 47 TC 22 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 20 PY 1992 VL 44 IS 8 BP 1651 EP 1660 DI 10.1016/0006-2952(92)90483-Y PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JW156 UT WOS:A1992JW15600023 PM 1417986 ER PT J AU DOMCHEK, SM AUGER, KR CHATTERJEE, S BURKE, TR SHOELSON, SE AF DOMCHEK, SM AUGER, KR CHATTERJEE, S BURKE, TR SHOELSON, SE TI INHIBITION OF SH2 DOMAIN PHOSPHOPROTEIN ASSOCIATION BY A NONHYDROLYZABLE PHOSPHONOPEPTIDE SO BIOCHEMISTRY LA English DT Article ID MIDDLE-T-ANTIGEN; PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; SOLID-PHASE SYNTHESIS; SIGNAL TRANSDUCTION; AMINO-ACIDS; ORTHO-PHTHALDIALDEHYDE; POLYOMA-VIRUS; TYROSINE; TRANSFORMATION; RECEPTOR AB Using the association between the pp60c-src/polyoma virus middle T antigen (mT) complex and phosphatidylinositol 3'-kinase (PI 3-kinase) as a prototype for phosphoprotein-SH2 domain interactions, we tested whether a nonhydrolyzable phosphonopeptide would inhibit association. (Phosphonomethyl)-phenylalanine (Pmp) is a nonnatural analogue of phosphotyrosine in which the >C-O-PO3H2 moiety is replaced by >C-CH2-PO3H2. We synthesized a 13 amino acid phosphonopeptide (mT-Pmp315), a related phosphopeptide (mT-pY315), and an unmodified sequence (mT-Y315), all corresponding to the pp60c-src-phosphorylated site of the mT which is within a YMXM motif common to proteins that bind to and activate PI 3-kinase. Only the phosphonopeptide persistently blocked the in vitro association of the baculovirus-expressed pp60c-src/mT complex with cytosolic PI 3-kinase activity. Sustained inhibition of association by the phosphopeptide required the additional presence of vanadate, a potent protein tyrosine phosphatase (PTPase) inhibitor. The phosphopeptide and L-phosphonopeptide bound tightly (K(D) almost-qual-to 10-20 nM) and specifically to isolated SH2 domains of PI 3-kinase p85, demonstrating that the mechanism of inhibited association is competitive binding to PI 3-kinase SH2 domains. We conclude that the appropriate phosphonopeptide sequence inhibits the interaction between a tyrosine-phosphorylated protein and a cognate SH2 domain-containing protein and is resistant to the actions of PTPases. Proteolytically stable phosphonopeptide derivatives should be useful inhibitors of protein-protein interactions when introduced into cells and may provide a basis for the rational design of a new class of chemotherapeutic agent. C1 JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NCI,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [DK08366] NR 42 TC 113 Z9 115 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 20 PY 1992 VL 31 IS 41 BP 9865 EP 9870 DI 10.1021/bi00156a002 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JU511 UT WOS:A1992JU51100002 PM 1382595 ER PT J AU QUON, MJ CAMA, A TAYLOR, SI AF QUON, MJ CAMA, A TAYLOR, SI TI POSTBINDING CHARACTERIZATION OF 5 NATURALLY-OCCURRING MUTATIONS IN THE HUMAN INSULIN-RECEPTOR GENE - IMPAIRED INSULIN-STIMULATED C-JUN EXPRESSION AND THYMIDINE INCORPORATION DESPITE NORMAL RECEPTOR AUTOPHOSPHORYLATION SO BIOCHEMISTRY LA English DT Article ID GROWTH FACTOR-I; TYROSINE KINASE; ALPHA-SUBUNIT; 3T3-L1 FIBROBLASTS; MUTANT ALLELES; CELL-SURFACE; RESISTANCE; TRANSPORT; TRANSFECTION; SUBSTITUTION AB Some patients with extreme insulin resistance have mutations in their insulin receptor gene. We previously identified five such mutations located in the extracellular domain of the insulin receptor (Asn-->Lys15, His-->Arg209, Phe-->Val382, Lys-Glu460, and Asn-->Ser462) and studied the effects of these mutations upon posttranslational processing, insulin binding, and tyrosine autophosphorylation. We now characterize the ability of these mutant receptors to mediate biological actions of insulin in transfected NIH-3T3 fibroblasts. All cell lines expressing mutant receptors showed marked impairment in insulin-stimulated c-jun expression and thymidine incorporation when compared with cells expressing wild-type human insulin receptors. The most severe impairment was seen in cells expressing the Val382 mutant (a mutation which causes an intrinsic defect in receptor autophosphorylation). These cells had insulin responses similar to the untransfected cells (used as a negative control). In contrast, cells expressing the Lys15 mutant have the ability to achieve a normal level of maximal autophosphorylation but require an abnormally high concentration of insulin to do so (as the result of decreased insulin binding affinity). These cells show a higher basal rate and much lower insulin stimulation of both c-jun expression and thymidine incorporation when compared with the cells expressing the wild-type human insulin receptors. This pattern is also seen in the cells expressing the other mutants with normal autophosphorylation (Arg209, Glu460, and Ser462). Although the most severe defects in insulin action are seen with the mutation which has an intrinsic defect in receptor autophosphorylation, the ability to undergo normal autophosphorylation does not seem to preclude mutations from impairing the ability of receptors to mediate some of the actions of insulin. C1 NIDDK,DIABET BRANCH,BLDG 10,ROOM 8S-239,BETHESDA,MD 20892. RI Quon, Michael/B-1970-2008; OI Quon , Michael /0000-0002-5289-3707 NR 38 TC 23 Z9 23 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 20 PY 1992 VL 31 IS 41 BP 9947 EP 9954 DI 10.1021/bi00156a013 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JU511 UT WOS:A1992JU51100013 PM 1390778 ER PT J AU PURI, A GRIMALDI, S BLUMENTHAL, R AF PURI, A GRIMALDI, S BLUMENTHAL, R TI ROLE OF VIRAL ENVELOPE SIALIC-ACID IN MEMBRANE-FUSION MEDIATED BY THE VESICULAR STOMATITIS-VIRUS ENVELOPE GLYCOPROTEIN SO BIOCHEMISTRY LA English DT Article ID G-PROTEIN; CELLS; PH; FLUORESCENCE; TRANSPORT; DEXTRAN; PLASMA; EVENTS AB Fusion of vesicular stomatitis virus (VSV) with cells and liposomes before and after treatment with neuraminidase was studied using the R18 dequenching assay. Desialylation of VSV significantly enhanced the extent of fusion with Vero cells but affected neither the pH dependence nor the binding of VSV to Vero cells. The enhanced fusion of asialo-VSV was observed both at the plasma membrane as well as via the endocytic pathway. Both VSV and asialo-VSV fused with liposomes made of neutral phospholipid, but only asialo-VSV fused with liposomes containing a 1:1 mixture of neutral and negatively charged phospholipid. To examine factors which contribute to the extent of fusion, we analyzed the various activation and inactivation reactions that take place as a result of low-pH triggering of VSV prebound to the target membrane. Lag times for the onset of fusion were similar for VSV and asialo-VSV, indicating that desialylation did not affect the activation reactions. However, exposure of VSV bound to target membranes at pH 6.5 for 400 s led to considerable inactivation, whereas little inactivation was seen after desialylation of VSV. These results are analyzed in terms of a model which allows us to determine which components of the overall fusion process are dominated by viral envelope sialic acid. C1 NCI,LMMB,MEMBRANE STRUCT & FUNCT SECT,BLDG 10,ROOM 4B56,BETHESDA,MD 20892. NR 33 TC 28 Z9 28 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 20 PY 1992 VL 31 IS 41 BP 10108 EP 10113 DI 10.1021/bi00156a034 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JU511 UT WOS:A1992JU51100034 PM 1327132 ER PT J AU LADENHEIM, EE JENSEN, RT MANTEY, SA MORAN, TH AF LADENHEIM, EE JENSEN, RT MANTEY, SA MORAN, TH TI DISTINCT DISTRIBUTIONS OF 2 BOMBESIN RECEPTOR SUBTYPES IN THE RAT CENTRAL-NERVOUS-SYSTEM SO BRAIN RESEARCH LA English DT Article DE BOMBESIN; GASTRIN-RELEASING PEPTIDE; NEUROMEDIN-B; RECEPTOR AUTORADIOGRAPHY; CENTRAL NERVOUS SYSTEM ID GASTRIN-RELEASING PEPTIDE; PANCREATIC ACINAR-CELLS; NEUROMEDIN-B; BINDING-SITES; BRAIN; LOCALIZATION; CLONING AB We have previously demonstrated the presence of two distinct bombesin receptor subtypes in the rat CNS and distinguished them as bombesin/gastrin-releasing peptide (BBS/GRP) and neuromedin B (NMB)-preferring binding sites. In the present study, we conduct a complete evaluation of the distribution of these binding sites throughout the rat brain using in vitro receptor autoradiography. The BBS/GRP-preferring binding sites were characterized as those that bound I-125-(Tyr4)BBS but not I-125-(D-Tyro)NMB. At these sites I-125-(Tyr4)BBS binding was inhibited in the presence of 100 nM BBS but not by the same concentration of NMB. In contrast, NMB-preferring sites bound both radioligands and binding at these sites was inhibited in the presence of 100 nM NMB. Our results indicate that the distributions of BBS/GRP and NMB-preferring binding sites are widespread and distinct at all levels of the rat brain suggesting these peptides mediate separate functions in the rat central nervous system. C1 NIDDKD,BETHESDA,MD 20892. RP LADENHEIM, EE (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,ROSS BLDG,RM 618,720 RUTLAND AVE,BALTIMORE,MD 21205, USA. NR 33 TC 63 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 16 PY 1992 VL 593 IS 2 BP 168 EP 178 DI 10.1016/0006-8993(92)91305-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA JV507 UT WOS:A1992JV50700003 PM 1333344 ER PT J AU HYDE, TM WU, LC KRASNOV, IB SIGWORTH, SK DAUNTON, NG DAMELIO, F AF HYDE, TM WU, LC KRASNOV, IB SIGWORTH, SK DAUNTON, NG DAMELIO, F TI QUANTITATIVE AUTORADIOGRAPHIC ANALYSIS OF MUSCARINIC CHOLINERGIC AND GABA(A) (BENZODIAZEPINE) RECEPTORS IN THE FOREBRAIN OF RATS FLOWN ON THE SOVIET BIOSATELLITE COSMOS 2044 SO BRAIN RESEARCH LA English DT Note DE AUTORADIOGRAPHY; GAMMA-AMINOBUTYRIC ACID; RECEPTOR; CHOLINERGIC; FOREBRAIN ID DIFFERENTIAL RESPONSE; STRIATAL DOPAMINE; BASAL GANGLIA; 6-HYDROXYDOPAMINE; LOCALIZATION; BRAIN; ORGANIZATION; SUBTYPES AB The quantitative autoradiographic analysis of muscarinic cholinergic and GABA(A) (benzodiazepine) receptors was performed on selected regions of the cerebral cortex and striatum of rats flown in the Soviet Biosatellite COSMOS 2044. An age- and strain-matched synchronous ground-based control group was employed for comparison. Muscarinic cholinergic receptor density was found to be significantly lower in the striatum of the flight animals as compared with that in the synchronous control group. No significant differences between flight and synchronous control groups were found in the other regions examined. GABA(A) (benzodiazepine) receptors showed no significant differences between the flight and control groups in any of the regions sampled. Although additional studies are needed to reach definitive conclusions, the decrease in muscarinic cholinergic receptors observed in the striatum suggests spaceflight-related alterations in motor activity. C1 NASA,AMES RES CTR,MAIL STOP 261-3,MOFFETT FIELD,CA 94035. NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. SAN JOSE STATE UNIV FDN,SAN JOSE,CA 95192. MOSCOW BIOMED PROBLEMS INST,MOSCOW,USSR. NR 18 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 16 PY 1992 VL 593 IS 2 BP 291 EP 294 DI 10.1016/0006-8993(92)91321-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA JV507 UT WOS:A1992JV50700019 PM 1333347 ER PT J AU MCMILLIAN, M HONG, JS PENNYPACKER, KR AF MCMILLIAN, M HONG, JS PENNYPACKER, KR TI PREFERENTIAL ACTIVATION OF [3H]PHORBOL-12,13-DIBUTYRATE BINDING BY AMPA (ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID) IN NEONATAL STRIATAL CELL-CULTURES SO BRAIN RESEARCH LA English DT Note DE AMPA; KAINATE; STRIATAL; GLUTAMATE; PHORBOL 12,13-DIBUTYRATE; EXCITATORY AMINO ACID RECEPTOR ID DEPENDENT PROTEIN-KINASE; HIPPOCAMPAL-NEURONS; GLUTAMATE RECEPTOR; KAINATE RECEPTORS; CYCLIC-AMP; RAT-BRAIN; QUISQUALATE; CLONING; LOCALIZATION; ENHANCEMENT AB Activation of excitatory amino acid receptors increased [H-3]phorbol-12,13-dibutyrate ([H-3]PdBu) binding in four week cultures of striatal cells from postnatal day 7 rat pups (PN7), and in PN7 cells co-cultured the fourth week with striatal cells from postnatal day 1 rat pups. Kainate (KA), trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), and N-methyl-D-aspartate (NMDA) increased [H-3]PdBu binding equally in both types of cultures, but alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) increased binding by 3-fold in the co-cultures. Thus, [H-3]PdBu binding in these two types of striatal cultures offers a simple model system for studying the regulation of AMPA/KA receptor responses. RP MCMILLIAN, M (reprint author), NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, NEUROPHARMACOL SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. RI Pennypacker, Keith/I-5092-2012 NR 29 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 16 PY 1992 VL 593 IS 2 BP 307 EP 310 DI 10.1016/0006-8993(92)91325-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA JV507 UT WOS:A1992JV50700023 PM 1280525 ER PT J AU ALTEMUS, M CIZZA, G GOLD, PW AF ALTEMUS, M CIZZA, G GOLD, PW TI CHRONIC FLUOXETINE TREATMENT REDUCES HYPOTHALAMIC VASOPRESSIN SECRETION INVITRO SO BRAIN RESEARCH LA English DT Note DE VASOPRESSIN; FLUOXETINE; HYPOTHALAMUS; OBSESSIVE-COMPULSIVE DISORDER ID WATER-EXCRETION; SEROTONIN AB Patients with obsessive-compulsive disorder (OCD) hypersecrete the arousal producing neurohormone arginine vasopressin (AVP) into the cerebrospinal fluid and plasma. Because OCD responds preferentially to potent serotonin uptake inhibitors, we compared the effect of chronic fluoxetine treatment to that of other antidepressants (trazodone and desipramine) on AVP release from rat hypothalamic organ culture and showed that only fluoxetine significantly reduced in vitro AVP release. C1 NIMH,DIV INTRAMURAL RES PROGRAMS,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 18 TC 44 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 16 PY 1992 VL 593 IS 2 BP 311 EP 313 DI 10.1016/0006-8993(92)91326-A PG 3 WC Neurosciences SC Neurosciences & Neurology GA JV507 UT WOS:A1992JV50700024 PM 1450938 ER PT J AU RICE, NR MACKICHAN, ML ISRAEL, A AF RICE, NR MACKICHAN, ML ISRAEL, A TI THE PRECURSOR OF NF-KAPPA-B P50 HAS I-KAPPA-B-LIKE FUNCTIONS SO CELL LA English DT Article ID REL ONCOGENE PRODUCT; DNA-BINDING SUBUNIT; TRANSFORMED LYMPHOID-CELLS; V-REL; RETICULOENDOTHELIOSIS VIRUS; TRANSCRIPTION FACTORS; CELLULAR PROTEINS; PHORBOL ESTER; 65-KD SUBUNIT; INHIBITION AB The C-terminal half of the p105 precursor of the NF-kappaB p50 subunit contains ankyrin-like repeats similar to those in IkappaB molecules, which are known to retain NF-kappaB complexes in the cytoplasm. We demonstrate that in various cell lines p105 is found associated with either c-rel or p65 in the cytoplasm and serves IkappaB-like functions. p105 retains c-rel or p65 in the cytoplasm in cotransfection experiments in COS cells. It also inhibits DNA binding by c-rel in gel retardation assays. Stable interaction of p105 with c-rel or p65 requires the putative dimerization domain in the conserved rel homology region of p105, as well as a second contact with the IkappaB-related C-terminal part of p105. Pulse-chase experiments indicate that cytoplasmic complexes of p105 with c-rel or p65 give rise to cytoplasmic as well as nuclear p50-c-rel and p50-p65, respectively, probably through processing of p105. Thus, p105, like the IkappaBs, controls the subcellular localization and hence the transcriptional activity of at least two other members of the rel/NF-kappaB family. C1 STANFORD UNIV,PROGRAM CANC BIOL,STANFORD,CA 94305. INST PASTEUR,UNITE BIOL MOLEC EXPRESS GENIQUE,F-75724 PARIS 15,FRANCE. RP RICE, NR (reprint author), FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [5T32 CA 09302, N01-CO-74101] NR 39 TC 411 Z9 414 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 16 PY 1992 VL 71 IS 2 BP 243 EP 253 DI 10.1016/0092-8674(92)90353-E PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JU395 UT WOS:A1992JU39500010 PM 1423592 ER PT J AU SHIVER, JW SU, LS HENKART, PA AF SHIVER, JW SU, LS HENKART, PA TI CYTOTOXICITY WITH TARGET DNA BREAKDOWN BY RAT BASOPHILIC LEUKEMIA-CELLS EXPRESSING BOTH CYTOLYSIN AND GRANZYME-A SO CELL LA English DT Article ID TOXIC LYMPHOCYTE-T; SERINE PROTEASE; PERFORIN; FRAGMENTATION; GRANULES; CLONING; LYSIS; ANTIBODY; BINDING; FAMILY AB The noncytotoxic rat mast cell tumor line RBL was transfected with genes for the cytotoxic lymphocyte granule proteins cytolysin (perforin) and granzyme A, giving transfectants with mRNA and protein expression levels comparable with cloned cytotoxic T lymphocytes. Both RBL-cytolysin and RBL-cytolysin-granzyme A transfectants showed extremely potent killing of red cell targets and lysed 20%-60% of EL4 lymphoma targets at an effector-to-target ratio of 30. RBL transfectants expressing only granzyme A were not cytotoxic. Significant EL4 DNA breakdown accompanying lysis was observed only with RBL that was transfected with both cytolysin and granzyme A. These results support the granule-exocytosis model for lymphocyte cytotoxicity and show that effector granzyme A plays a role in target cell DNA breakdown. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. STANFORD UNIV,MED CTR,SCH MED,DEPT PATHOL,STANFORD,CA 94305. NR 35 TC 231 Z9 233 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 16 PY 1992 VL 71 IS 2 BP 315 EP 322 DI 10.1016/0092-8674(92)90359-K PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JU395 UT WOS:A1992JU39500016 PM 1423596 ER PT J AU PELTONEN, K CANELLA, K DIPPLE, A AF PELTONEN, K CANELLA, K DIPPLE, A TI HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC SEPARATION OF PURINE DEOXYRIBONUCLEOSIDE MONOPHOSPHATE BENZO[A]PYRENE ADDUCTS SO JOURNAL OF CHROMATOGRAPHY LA English DT Article ID MAMMALIAN-CELLS; DNA ADDUCTS; METABOLIC ACTIVATION; DIHYDRODIOL EPOXIDE; DIOL-EPOXIDE; CARCINOGENESIS; BENZO(A)PYRENE; IDENTIFICATION AB Chromatographic methods that allow the separation of adducts of purine nucleoside 3'-phosphates with the pure enantiomers of the anti-dihydrodiol epoxide of benzo[a]pyrene are developed. The optimization procedure includes evaluation of the effect of buffer molarity, the pH of the buffer, and the role of organic modifiers. The method can be utilized to prepare standards with known absolute configuration that can be further used in the Randerath P-32-postlabeling procedure. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM & CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 21 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD OCT 16 PY 1992 VL 623 IS 2 BP 247 EP 254 DI 10.1016/0021-9673(92)80364-Z PG 8 WC Chemistry, Analytical SC Chemistry GA JV296 UT WOS:A1992JV29600005 PM 1460077 ER PT J AU WEINSTEIN, JN KOHN, KW GREVER, MR VISWANADHAN, VN RUBINSTEIN, LV MONKS, AP SCUDIERO, DA WELCH, L KOUTSOUKOS, AD CHIAUSA, AJ PAULL, KD AF WEINSTEIN, JN KOHN, KW GREVER, MR VISWANADHAN, VN RUBINSTEIN, LV MONKS, AP SCUDIERO, DA WELCH, L KOUTSOUKOS, AD CHIAUSA, AJ PAULL, KD TI NEURAL COMPUTING IN CANCER DRUG DEVELOPMENT - PREDICTING MECHANISM OF ACTION SO SCIENCE LA English DT Article ID TUMOR-CELL-LINES; ARTIFICIAL-INTELLIGENCE; NETWORKS; DIAGNOSIS; RECOGNITION; FEASIBILITY; BINDING; ERRORS; SITES; ASSAY AB Described here are neural networks capable of predicting a drug's mechanism of action from its pattern of activity against a panel of 60 malignant cell lines in the National Cancer Institute's drug screening program. Given six possible classes of mechanism, the network misses the correct category for only 12 out of 141 agents (8.5 percent), whereas linear discriminant analysis, a standard statistical technique, misses 20 out of 141 (14.2 percent). The success of the neural net indicates several things. (i) The cell line response patterns are rich in information about mechanism. (ii) Appropriately designed neural networks can make effective use of that information. (iii) Trained networks can be used to classify prospectively the more than 10,000 agents per year tested by the screening program. Related networks, in combination with classical statistical tools, will help in a variety of ways to move new anticancer agents through the pipeline from in vitro studies to clinical application. C1 NCI,DIV CANC BIOL DIAG & CTR,MATH BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BIOMETR RES BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. RP WEINSTEIN, JN (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C-25,BETHESDA,MD 20892, USA. NR 34 TC 233 Z9 236 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 16 PY 1992 VL 258 IS 5081 BP 447 EP 451 DI 10.1126/science.1411538 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT775 UT WOS:A1992JT77500030 PM 1411538 ER PT J AU JENKINS, TM SAXENA, JK KUMAR, A WILSON, SH ACKERMAN, EJ AF JENKINS, TM SAXENA, JK KUMAR, A WILSON, SH ACKERMAN, EJ TI DNA POLYMERASE-BETA AND DNA-SYNTHESIS IN XENOPUS OOCYTES AND IN A NUCLEAR EXTRACT SO SCIENCE LA English DT Article ID TEMPLATE BINDING DOMAIN; SINGLE-STRANDED-DNA; REPAIR SYNTHESIS; HUMAN-CELLS; ALPHA; REPLICATION; LAEVIS; DELTA; EGGS; IDENTIFICATION AB The identities of the DNA polymerases required for conversion of single-strand (ss) M13 DNA to double-strand (ds) M13 DNA were examined both in injected Xenopus laevis oocytes and in an oocyte nuclear extract. Inhibitors and antibodies specific to DNA polymerases alpha and beta were used. In nuclear extracts, inhibition by the antibody to polymerase beta could be reversed by purified polymerase beta. The polymerase beta inhibitors, dideoxythymidine triphosphate (ddTTP) and dideoxycytidine triphosphate (ddCTP), also blocked DNA synthesis and indicated that polymerase beta is invoLved in the conversion of ssDNA to dsDNA. These results also may have particular significance for emerging evidence of an ssDNA replication mode in eukaryotic cells. C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 39 TC 52 Z9 53 U1 1 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 OCT 16 PY 1992 VL 258 IS 5081 BP 475 EP 478 DI 10.1126/science.1411545 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT775 UT WOS:A1992JT77500039 PM 1411545 ER PT J AU GALDERISI, M LAUER, MS LEVY, D AF GALDERISI, M LAUER, MS LEVY, D TI ECHOCARDIOGRAPHIC DETERMINANTS OF CLINICAL OUTCOME IN SUBJECTS WITH CORONARY-ARTERY DISEASE (THE FRAMINGHAM HEART-STUDY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR MASS; ACUTE MYOCARDIAL-INFARCTION; MEDICALLY TREATED PATIENTS; SURVIVAL; HYPERTROPHY; RECOVERY; ASYNERGY; VOLUME AB Echocardiographic predictors of clinical outcome were examined in subjects from the Framingham Heart Study with overt coronary artery disease. The study population consisted of 185 men and 147 women with coronary artery disease who underwent M-mode echocardiography and were followed for a mean of 3.90 years. At baseline, 37 men (18.4%) and 16 women (10.9%) had reduced fractional shortening, 43 men (23.2%) and 28 women (19%) had left ventricular (LV) dilatation, and 76 men (41%) and 76 women (51.7%) had LV hypertrophy. During the follow-up period new cardiovascular disease events (coronary disease, stroke, transient ischemic attack, claudication, heart failure and deaths from cardiovascular disease) occurred in 60 men (32%) and 58 women (39%). With use of age-adjusted proportional hazards analyses, LV mass/height in men (relative risk [RR] = 1.2S/SO g/m increment, 95% confidence interval [CI] 1.01 to 1.55) and LV end-diastolic diameter in women (RR = 1.36/5 mm increment, 95% CI 1.05 to 1.76) were predictors of new cardiovascular disease events. Cardiovascular risk was also associated with LV end-systolic diameter in both sexes (in men RR = 1.28/1 SD increment, 95% CI 1.02 to 1.63; in women RR 1.40/1 standard deviation increment, 95% CI 1.09 to 1.82). Reduced fractional shortening alone (RR = 1.91, 95% CI 1.11 to 3.3 1) and in combination with LV dilatation (RR = 2.13, 95% CI 1.13 to 4.02) was associated with the incidence of new cardiovascular disease outcomes in men. In women, cardiovascular risk was increased with LV hypertrophy (RR = 2.30, 95% CI 1.29 to 4.12), high LV wall thickness (RR 3.36 95% CI = 1.18 to 9.55), high LV end-systolic diameter (RR = 2.59, 95% CI 1.45 to 4.62) and a combination of low fractional shortening and LV dilatation (RR = 3.25, 95% CI 1.28 to 8.25). Thus, M-mode echocardiography has prognostic value in identifying subjects with coronary artery disease who are at increased risk for new morbid or fatal events. C1 NHLBI,FRAMINGHAM HEART STUDY,5 THURBER ST,FRAMINGHAM,MA 01701. BETH ISRAEL HOSP,DEPT CARDIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT CLIN EPIDEMIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. LAHEY CLIN MED CTR,BURLINGTON,MA. BOSTON UNIV,SCH MED,EPIDEMIOL & PREVENT MED SECT,BOSTON,MA 02118. RI Lauer, Michael/L-9656-2013; OI Lauer, Michael/0000-0002-9217-8177; Galderisi, Maurizio/0000-0003-0311-9069 NR 23 TC 43 Z9 43 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 1992 VL 70 IS 11 BP 971 EP 976 DI 10.1016/0002-9149(92)90345-Y PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JT347 UT WOS:A1992JT34700001 PM 1414914 ER PT J AU GLICK, BN ROBERTS, WC AF GLICK, BN ROBERTS, WC TI USEFULNESS OF TOTAL 12-LEAD QRS VOLTAGE IN DIAGNOSING LEFT-VENTRICULAR HYPERTROPHY IN CLINICALLY ISOLATED, PURE, CHRONIC, SEVERE MITRAL REGURGITATION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID IDIOPATHIC DILATED CARDIOMYOPATHY; NECROPSY PATIENTS; DISEASE; CRITERIA C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP GLICK, BN (reprint author), NHLBI,PATHOL BRANCH,BETHESDA,MD 20892, USA. NR 13 TC 5 Z9 5 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 OCT 15 PY 1992 VL 70 IS 11 BP 1088 EP 1092 DI 10.1016/0002-9149(92)90368-9 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JT347 UT WOS:A1992JT34700024 PM 1414910 ER PT J AU GUTKIND, JS ROBBINS, KC AF GUTKIND, JS ROBBINS, KC TI ACTIVATION OF TRANSFORMING G-PROTEIN-COUPLED RECEPTORS INDUCES RAPID TYROSINE PHOSPHORYLATION OF CELLULAR PROTEINS, INCLUDING P125FAK AND THE P130 V-SRC SUBSTRATE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID KINASES; PLATELETS RP GUTKIND, JS (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892, USA. RI Gutkind, J. Silvio/A-1053-2009 NR 14 TC 50 Z9 52 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 15 PY 1992 VL 188 IS 1 BP 155 EP 161 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JU247 UT WOS:A1992JU24700023 PM 1329743 ER PT J AU MURAMATSU, T KINCAID, RL AF MURAMATSU, T KINCAID, RL TI MOLECULAR-CLONING AND CHROMOSOMAL MAPPING OF THE HUMAN GENE FOR THE TESTIS-SPECIFIC CATALYTIC SUBUNIT OF CALMODULIN-DEPENDENT PROTEIN PHOSPHATASE (CALCINEURIN-A) SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID IDENTIFICATION; DOMAIN; PHOSPHORYLATION RP NIAAA, MOLEC & CELLULAR NEUROBIOL LAB, IMMUNOL SECT, ROCKVILLE, MD 20852 USA. NR 17 TC 49 Z9 50 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 15 PY 1992 VL 188 IS 1 BP 265 EP 271 DI 10.1016/0006-291X(92)92379-C PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JU247 UT WOS:A1992JU24700039 PM 1339277 ER PT J AU YOGANATHAN, T BHAT, NK SELLS, BH AF YOGANATHAN, T BHAT, NK SELLS, BH TI A POSITIVE REGULATOR OF THE RIBOSOMAL-PROTEIN GENE, BETA-FACTOR, BELONGS TO THE ETS ONCOPROTEIN FAMILY SO BIOCHEMICAL JOURNAL LA English DT Article ID OOCYTE TRANSCRIPTION FACTOR; HIGHLY CONSERVED PROTEINS; DNA-BINDING; XENOPUS-LAEVIS; MAMMALIAN ETS-1; EXPRESSED GENE; SEQUENCE; ACTIVATION; ONCOGENE; PROMOTER AB The beta factor, which interacts with the rpL32 promoter, binds to the sequence 5'-GAGCCGGAAGTG and trans-activates this gene. Comparison of the DNA sequences bound by the beta factor with those bound by other known DNA-binding proteins revealed that the ETS proteins interact with similar DNA sequences. Consequently we have examined the relationship of the beta factor to the several ETS proteins so far reported. Antibody and oligonucleotide competition experiments, performed by using electrophoretic shift analysis, revealed that the beta factor contains ETS epitopes and that it is immunologically related to both of the GA-binding proteins (GABPs), implying that the beta factor may consist of two separate protein subunits. C1 UNIV GUELPH,COLL BIOL SCI,DEPT MOLEC BIOL & GENET,GUELPH N1G 2W1,ONTARIO,CANADA. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,MOLEC ONCOL LAB,FREDERICK,MD 21702. NR 41 TC 22 Z9 22 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 OCT 15 PY 1992 VL 287 BP 349 EP 353 PN 2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JU572 UT WOS:A1992JU57200002 PM 1445193 ER PT J AU KLEIN, HG AF KLEIN, HG TI WOLF IN WOLFS CLOTHING - IS IT TIME TO RAISE THE BOUNTY ON THE PASSENGER LEUKOCYTE SO BLOOD LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN CYTOMEGALO-VIRUS; BLOOD-TRANSFUSION; T-CELLS; PLATELET REFRACTORINESS; RED-CELLS; INFECTION; ACTIVATION; PREVENTION; AIDS RP KLEIN, HG (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,RM 1C711,BETHESDA,MD 20892, USA. NR 48 TC 38 Z9 38 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 OCT 15 PY 1992 VL 80 IS 8 BP 1865 EP 1868 PG 4 WC Hematology SC Hematology GA JT776 UT WOS:A1992JT77600001 PM 1391950 ER PT J AU LINNEKIN, D PARK, LS FARRAR, WL AF LINNEKIN, D PARK, LS FARRAR, WL TI DISSOCIATION OF HUMAN CYTOKINE RECEPTOR EXPRESSION AND SIGNAL TRANSDUCTION SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; PROMYELOCYTIC LEUKEMIA-CELLS; HEMATOPOIETIC GROWTH-FACTORS; TYROSINE PHOSPHORYLATION; GM-CSF; INTERLEUKIN-2 RECEPTOR; BETA-SUBUNIT; ERYTHROPOIETIN RECEPTOR; DIMETHYL-SULFOXIDE; PROTEIN-KINASE C1 IMMUNEX RES & DEV CORP,DEPT BIOCHEM,SEATTLE,WA. RP LINNEKIN, D (reprint author), NCI,FREDERICK CANC RES CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,BLDG 560,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 41 TC 17 Z9 17 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 OCT 15 PY 1992 VL 80 IS 8 BP 1896 EP 1904 PG 9 WC Hematology SC Hematology GA JT776 UT WOS:A1992JT77600006 PM 1382709 ER PT J AU SPANGRUDE, GJ BROOKS, DM AF SPANGRUDE, GJ BROOKS, DM TI PHENOTYPIC ANALYSIS OF MOUSE HEMATOPOIETIC STEM-CELLS SHOWS A THY-1-NEGATIVE SUBSET SO BLOOD LA English DT Article ID COLONY-FORMING CELLS; CFU-S CELL; MONOCLONAL-ANTIBODIES; BONE-MARROW; T-CELLS; COMPETITIVE REPOPULATION; B-CELL; PRECURSORS; ANTIGEN; SEPARATION RP SPANGRUDE, GJ (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 42 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 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 1992 VL 80 IS 8 BP 1957 EP 1964 PG 8 WC Hematology SC Hematology GA JT776 UT WOS:A1992JT77600013 PM 1356513 ER PT J AU LEVY, DD GROOPMAN, JD LIM, SE SEIDMAN, MM KRAEMER, KH AF LEVY, DD GROOPMAN, JD LIM, SE SEIDMAN, MM KRAEMER, KH TI SEQUENCE SPECIFICITY OF AFLATOXIN B(1)-INDUCED MUTATIONS IN A PLASMID REPLICATED IN XERODERMA-PIGMENTOSUM AND DNA-REPAIR PROFICIENT HUMAN-CELLS SO CANCER RESEARCH LA English DT Article ID SHUTTLE-VECTOR; P53 GENE; HEPATOCELLULAR-CARCINOMA; HUMAN-FIBROBLASTS; EXCISION REPAIR; HUMAN CANCERS; LIVER-TUMORS; BASE; SPECTRUM; ADDUCTS AB The mutagenic spectrum induced by aflatoxin-DNA lesions in DNA repair deficient and repair proficient human cells was investigated. The reactive metabolite aflatoxin B1-8,9-epoxide was synthesized and reacted in vitro with the shuttle vector plasmid pS189. Plasmids were transfected into human fibroblasts and allowed to replicate, and the recovered plasmids were screened in indicator bacteria for plasmid survival and mutations in the supF marker gene. Sequence data were obtained from 71 independently arising mutants recovered from DNA repair deficient xeroderma pigmentosum (XP) cells [XP12BE(SV40)] and 60 mutants recovered from a DNA repair proficient cell line (GM0637). Plasmid survival was lower and mutation frequency higher with the XP cells, and the mutation hotspots differed substantially for the 2 cell lines. Most mutations (>90%) were base substitutions at G:C pairs, only about one-half of which were G:C --> T:A transversions, the expected predominant mutation. One-third of the mutations at GG sites and none of those at isolated Gs were G:C --> A:T transitions. Tandem base substitutions also occurred only at GG sites and were found only with XP cells. The location of mutation hotspots with either cell line did not correlate with the level of modification within the sequence as assessed by a DNA polymerase stop assay. These results suggest that the DNA repair deficiency associated with XP can influence not only the overall frequency of mutations but also the distribution of mutations within a gene. The finding of transition mutations exclusively at GG sites may be of predictive value in attempts to link dietary aflatoxin exposure to cancers associated with specific mutations in the c-ras oncogene and the p53 tumor suppressor gene. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. OTSUKA PHARMACEUT CO LTD,ROCKVILLE,MD 20850. FU Intramural NIH HHS [Z01 BC004517-31] NR 39 TC 84 Z9 86 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 OCT 15 PY 1992 VL 52 IS 20 BP 5668 EP 5673 PG 6 WC Oncology SC Oncology GA JU458 UT WOS:A1992JU45800014 PM 1394191 ER PT J AU HUNEKE, RB PIPPIN, CG SQUIRE, RA BRECHBIEL, MW GANSOW, OA STRAND, M AF HUNEKE, RB PIPPIN, CG SQUIRE, RA BRECHBIEL, MW GANSOW, OA STRAND, M TI EFFECTIVE ALPHA-PARTICLE-MEDIATED RADIOIMMUNOTHERAPY OF MURINE LEUKEMIA SO CANCER RESEARCH LA English DT Note ID MONOCLONAL-ANTIBODY; ERYTHROLEUKEMIC MICE; EMITTING RADIONUCLIDES; CANCER AB The specificity, toxicity, and efficacy of alpha-particle-mediated radioimmunotherapy of murine erythroleukemia was assessed by use of tumor-specific monoclonal antibody 103A labeled with Bi-212. Forty % of the injected dose/g tissue targeted to neoplastic spleens within 1 h after i.v. injection. When Bi-212-103A was injected on day 13 of disease, a dose-dependent response was achieved, as measured by a reduction in splenomegaly and absence of liver metastasis. Mice treated With Bi-212-103A on day 8 of disease showed no histological evidence of erythroleukemia on day 22 and survived significantly longer (median, 118 days) than mice treated with Bi-212-control IgG (78 days) or untreated mice (63 days), indicating successful specific radioimmunotherapy. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT COMPARAT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL,BALTIMORE,MD 21205. NCI,RADIAT ONCOL BRANCH,INORGAN & RADIOIMMUNE CHEM SECT,BETHESDA,MD 20892. FU NCRR NIH HHS [RR00130, RR007002] NR 19 TC 75 Z9 76 U1 0 U2 3 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 OCT 15 PY 1992 VL 52 IS 20 BP 5818 EP 5820 PG 3 WC Oncology SC Oncology GA JU458 UT WOS:A1992JU45800039 PM 1394209 ER PT J AU EMONARD, HP REMACLE, AG NOEL, AC GRIMAUD, JA STETLERSTEVENSON, WG FOIDART, JM AF EMONARD, HP REMACLE, AG NOEL, AC GRIMAUD, JA STETLERSTEVENSON, WG FOIDART, JM TI TUMOR-CELL SURFACE-ASSOCIATED BINDING-SITE FOR THE M(R)72,000 TYPE-IV COLLAGENASE SO CANCER RESEARCH LA English DT Note ID HUMAN CANCER-CELLS; PLASMINOGEN-ACTIVATOR; PLASMA-MEMBRANES; STROMAL CELLS; GELATINASE; PROENZYME; RECEPTOR AB We have studied the capacity of two human breast adenocarcinoma cells, MDA-MB231 and MCF-7, to bind exogenous M(r) 72,000 type IV collagenase by both morphological and radioreceptor binding assays. By indirect immunofluorescence, staining with a specific anti-M(r) 72,000 type IV collagenase antibody was strongly induced when cells were preincubated with the purified enzyme. Scatchard plot analysis indicated the existence of a binding site for the M(r) 72,000 type IV collagenase with high affinity for both cell lines (K(d) = 2 x 10(-9) M). These results are the first demonstration of the existence of a tumor cell membrane-associated putative receptor for a member of the matrix metalloproteinase family, as previously evidenced for the urokinase-type plasminogen activator. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. INST PASTEUR,CNRS,URA 1459,LYON,FRANCE. RP EMONARD, HP (reprint author), UNIV LIEGE,BIOL LAB,TOWER PATHOL B23,SART TILMAN,B-4000 LIEGE,BELGIUM. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Noel, Agnes/0000-0002-7670-6179 NR 19 TC 186 Z9 187 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 OCT 15 PY 1992 VL 52 IS 20 BP 5845 EP 5848 PG 4 WC Oncology SC Oncology GA JU458 UT WOS:A1992JU45800045 PM 1394213 ER PT J AU BOULAY, JL PAUL, WE AF BOULAY, JL PAUL, WE TI THE INTERLEUKIN-4-RELATED LYMPHOKINES AND THEIR BINDING TO HEMATOPOIETIN RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID COLONY-STIMULATING FACTOR; GROWTH-FACTOR RECEPTORS; CYTOKINE GENE-CLUSTER; GM-CSF GENES; MOLECULAR-CLONING; BETA-CHAIN; ERYTHROPOIETIN RECEPTOR; 3-DIMENSIONAL STRUCTURE; EXPRESSION CLONING; SIGNAL TRANSDUCER RP BOULAY, JL (reprint author), NIAID,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 58 TC 56 Z9 57 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1992 VL 267 IS 29 BP 20525 EP 20528 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800001 PM 1400369 ER PT J AU METZ, DC PATTO, RJ MROZINSKI, JE JENSEN, RT TURNER, RJ GARDNER, JD AF METZ, DC PATTO, RJ MROZINSKI, JE JENSEN, RT TURNER, RJ GARDNER, JD TI THAPSIGARGIN DEFINES THE ROLES OF CELLULAR CALCIUM IN SECRETAGOGUE-STIMULATED ENZYME-SECRETION FROM PANCREATIC ACINI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FREE CYTOSOLIC CALCIUM; GUINEA-PIG PANCREAS; AMYLASE RELEASE; INOSITOL TRISPHOSPHATE; TUMOR PROMOTER; PLASMA-MEMBRANE; SIGNAL TRANSDUCTION; EXOCRINE PANCREAS; DISPERSED ACINI; CYCLIC-AMP AB In the present study we used thapsigargin (TG), an inhibitor of microsomal calcium ATPase, to evaluate the roles of free cytoplasmic calcium and intracellular stored calcium in secretagogue-stimulated enzyme secretion from rat pancreatic acini. Using microspectro-fluorimetry of fura-2-loaded pancreatic acini, we found that TG caused a sustained increase in free cytoplasmic calcium by mobilizing calcium from inositol 1, 4, 5-trisphosphate-sensitive intracellular stores and by increasing influx of extracellular calcium. TG also caused a small increase in basal amylase secretion, inhibited the stimulation of amylase secretion caused by secretagogues that increase inositol 1, 4, 5-trisphosphate, and potentiated the stimulation of amylase secretion caused by 12-O-tetradecanoylphorbol-13-acetate or secretagogues that increase cyclic adenosine 3',5'-monophosphate. Bombesin, which like TG increased free cytoplasmic calcium, also potentiated the stimulation of amylase secretion caused by secretagogues that increase cyclic adenosine 3',5'-monophosphate, but did not inhibit the stimulation of amylase secretion caused by secretagogues that increase inositol 1, 4, 5-trisphosphate. Finally, TG inhibited the sustained phase of cholecystokinin-stimulated amylase secretion and potentiated the time course of vasoactive intestinal peptide-stimulated amylase secretion. The present findings indicate that stimulation of amylase secretion by secretagogues that increase inositol 1, 4, 5-trisphosphate does not depend on increased free cytoplasmic calcium per se. In contrast, TG-induced potentiation of the stimulation of secretagogues that increase cellular cyclic adenosine 3',5'-monophosphate appears to result from increased free cytoplasmic calcium per se. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 63 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1992 VL 267 IS 29 BP 20620 EP 20629 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800021 PM 1383205 ER PT J AU KAZANIETZ, MG KRAUSZ, KW BLUMBERG, PM AF KAZANIETZ, MG KRAUSZ, KW BLUMBERG, PM TI DIFFERENTIAL IRREVERSIBLE INSERTION OF PROTEIN-KINASE-C INTO PHOSPHOLIPID-VESICLES BY PHORBOL ESTERS AND RELATED ACTIVATORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE-BRAIN CYTOSOL; TUMOR-PROMOTING ACTIVITIES; 6TH RHOADS MEMORIAL; 12,13-DIBUTYRATE BINDING; 12-MYRISTATE 13-ACETATE; CELLULAR-REGULATION; SYNTHETIC ANALOGS; RAT-BRAIN; MEMBRANE; RECEPTOR AB Incubation of protein kinase C (PKC) alpha with phorbol 12,13-dibutyrate and phospholipid vesicles promoted a time-dependent irreversible insertion of the enzyme into the vesicles and the generation of a calcium-independent kinase activity. Calcium neither caused insertion nor influenced the insertion induced by the phorbol ester. The effect was strongly dependent on the phosphatidylserine concentration in the vesicle and could also be supported by other anionic phospholipids. An analysis of the structure-activity relations of PKC activators for the calcium-independent kinase activity revealed marked relative differences in potencies for binding and for insertion. Compounds such as phorbol 13-myristate 12-acetate and mezerein were very efficient at inducing insertion. In contrast, 12-deoxyphorbol esters and diacylglycerol were relatively inefficient at inducing insertion, requiring higher concentrations than expected from their binding affinities. The insertion of PKC alpha depended substantially on the length of the aliphatic esters in the 12- and 13-positions of the phorbol derivatives, and once again, potencies for insertion and binding were not directly proportional. Our findings suggest two different sites for ligand interaction on the molecule of PKC alpha with different structure-activity requirements. We speculate that the differential ability of compounds to promote insertion could contribute to the documented marked differences in the biological behavior of PKC activators. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 44 TC 87 Z9 87 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1992 VL 267 IS 29 BP 20878 EP 20886 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800058 PM 1400402 ER PT J AU GANGULY, C BAINES, IC KORN, ED SELLERS, J AF GANGULY, C BAINES, IC KORN, ED SELLERS, J TI REGULATION OF THE ACTIN-ACTIVATED ATPASE AND INVITRO MOTILITY ACTIVITIES OF MONOMERIC AND FILAMENTOUS ACANTHAMOEBA MYOSIN-II SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; 3 PHOSPHORYLATION SITES; AMINO-ACID-SEQUENCE; HEAVY-CHAIN; CYTOPLASMIC MYOSINS; LIGHT CHAIN; PURIFICATION; TAIL; QUANTITATION; CASTELLANII AB The actin-activated Mg2+-ATPase activity of filamentous Acanthamoeba myosin II is inhibited by phosphorylation of 3 serine residues at the tip of the tail of each heavy chain. From previous studies, it had been concluded that the activity of each molecule in the filament was regulated by the global state of phosphorylation of the filament and was independent of its own phosphorylation state. The actin-activated Mg2+-ATPase activity of monomeric phosphorylated myosin II was not known because it polymerizes under the ionic conditions necessary for the expression of this activity. We have now found conditions to maintain myosin II monomeric and active during the enzyme assay. The actin-activated Mg2+-ATPase activities of monomeric dephosphorylated and phosphorylated myosin II were found to be the same as the activity of filamentous dephosphorylated myosin II. These results support the conclusion that phosphorylation regulates filamentous myosin II by affecting filament conformation. Consistent with their equivalent enzymatic activities, monomeric and filamentous dephosphorylated myosin II were equally active in an in vitro motility assay in which myosin adsorbed to a surface drives the movement of F-actin. In contrast to their very different enzymatic activities, however, filamentous and monomeric phosphorylated myosin II had similar activities in the in vitro motility assay; both were much less active than monomeric and filamentous dephosphorylated myosin II. One interpretation of these results is that the rate-limiting steps in the two assays are different and that, while the rate-limiting step for actin-activated Mg2+-ATPase activity is regulated only at the level of the filament, the rate-limiting step for motility can also be regulated at the level of the monomer. C1 NHLBI,CELL BIOL LAB,BLDG 3,RM B122,BETHESDA,MD 20892. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012 NR 33 TC 21 Z9 21 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 OCT 15 PY 1992 VL 267 IS 29 BP 20900 EP 20904 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800061 PM 1400404 ER PT J AU GANGULY, C MARTIN, B BUBB, M KORN, ED AF GANGULY, C MARTIN, B BUBB, M KORN, ED TI LIMITED PROTEOLYSIS REVEALS A STRUCTURAL DIFFERENCE IN THE GLOBULAR HEAD DOMAINS OF DEPHOSPHORYLATED AND PHOSPHORYLATED ACANTHAMOEBA MYOSIN-II SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; TAIL; CONFORMATION; CHAIN; CASTELLANII; MOLECULES; SEQUENCE; ACTIN AB Phosphorylation at three sites at the tip of the tail of myosin II from Acanthamoeba castellanii inactivates the actin-activated Mg2+-ATPase activity of filamentous myosin and the in vitro motility activity of both monomeric and filamentous myosin. To seek a structural explanation for these effects, we examined the susceptibilities of dephosphorylated and phosphorylated myosins II to endoproteinases. Endoproteinase Arg-C cleaved myosin II preferentially at two sites in the globular head, Lys-621 and Arg-638, producing an NH2-terminal fragment of about 67,000 Da and a COOH-terminal fragment of about 112,000 Da. Dephosphorylated monomers and filaments were cleaved about 3 times more rapidly than their phosphorylated counterparts principally because of a much greater rate of cleavage at Arg-638; the ratio of cleavage at Arg-638:Lys-621 was about 3 for dephosphorylated myosins and about 0.5 for phosphorylated myosins. These data demonstrate that phosphorylation at the tip of the tail of Acanthamoeba myosin II causes a conformational change in the globular head that contains the catalytic sites; therefore, this conformational change may be related to the different catalytic and motile activities of the dephosphorylated and phosphorylated enzymes. C1 NHLBI,CELL BIOL LAB,BLDG 3,RM B1-22,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012 NR 18 TC 14 Z9 15 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1992 VL 267 IS 29 BP 20905 EP 20908 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800062 PM 1400405 ER PT J AU BRUGGEMANN, EP CURRIER, SJ GOTTESMAN, MM PASTAN, I AF BRUGGEMANN, EP CURRIER, SJ GOTTESMAN, MM PASTAN, I TI CHARACTERIZATION OF THE AZIDOPINE AND VINBLASTINE BINDING-SITE OF P-GLYCOPROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANT CELLS; BACTERIAL TRANSPORT PROTEINS; DEPENDENT TRANSPORT; PHOTOAFFINITY PROBE; MEMBRANE-VESICLES; CYSTIC-FIBROSIS; H-3 AZIDOPINE; DRUG-BINDING; TUMOR-CELLS; KB CELLS AB To determine the number of drug binding sites that exist on the multidrug transporter, P-glycoprotein, we used azidopine, a dihydropyridine photoaffinity compound that reverses multidrug resistance and labels P-glycoprotein. Azidopine labels P-glycoprotein in two distinct locations: one labeled site is within the amino half of P-glycoprotein between amino acid residues 198 and 440, and the other site is within the carboxy half of the protein. Vinblastine is a cytotoxic drug that is used in cancer chemotherapy and is a substrate for transport by P-glycoprotein. We found that vinblastine inhibits azidopine labeling to approximately the same extent at each labeled site on P-glycoprotein. Because several studies have shown that amino acid residue 185 of P-glycoprotein plays a critical role in some aspects of drug binding and transport, we also studied the effect that amino acid residue 185 has on azidopine labeling. These studies show that azidopine labels both sites equivalently in both wild-type (G185) and mutant (V185) P-glycoproteins. We conclude from our results that the two halves of P-glycoprotein approach each other to form a single binding site for these drugs. C1 NCI,MOLEC BIOL LAB,BLDG 37,RM 4E16,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 50 TC 184 Z9 185 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 OCT 15 PY 1992 VL 267 IS 29 BP 21020 EP 21026 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800080 PM 1356986 ER PT J AU SARTOR, O MCLELLAN, CA CHIUEH, T AF SARTOR, O MCLELLAN, CA CHIUEH, T TI COMPARISON OF SRC-FAMILY CDNAS REVEALS DISTINCT MECHANISMS UNDERLYING FOCUS FORMATION IN TRANSFECTED FIBROBLASTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; NIH 3T3 CELLS; CHICKEN-EMBRYO FIBROBLASTS; RETROVIRUS SHUTTLE VECTOR; AVIAN-SARCOMA VIRUSES; C-SRC; CELLULAR PROTEINS; GENE-PRODUCT; RAT-CELLS; PP60C-SRC AB Despite the intensive study of both cellular transformation and src-family protein-tyrosine kinases, there have been no direct comparisons of transforming potency for normal members of this gene-family. In this study, the focus-forming activity of normal c-src, fyn, and lck cDNAs were compared in NIH 3T3 cell transfection assays. Focus formation was studied quantitatively, and individual foci were analyzed for phosphotyrosine content and expression of appropriate translational products. Each foci arising from c-src transfectants had a marked increase in phosphotyrosine content, and the majority of these foci expressed a c-src protein with an aberrant carboxyl terminus. Foci derived from lck transfectants also had a marked increase in phosphotyrosine content, and some foci expressed a lck protein with an aberrant carboxyl terminus. In contrast, foci from fyn-transfected cells were not distinguished from G418-selected mass cultures in terms of total phosphotyrosine content or expression of p59fyn. These studies support the previously published concept that overexpression of the normal fyn protein contributes to focus formation in transfected NIH 3T3 cells but suggest that the focus-forming activity observed after c-src or lck transfections is frequently attributable to mutational events. Because lck mutations have not been previously described in transformed foci, we characterized the lck transcript expressed in two foci and identified a novel point mutation that encodes a lck protein with increased in vivo kinase and focus-forming activity. RP SARTOR, O (reprint author), NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,RM 12N226,BLDG 10,BETHESDA,MD 20892, USA. NR 48 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1992 VL 267 IS 29 BP 21044 EP 21051 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800084 PM 1383216 ER PT J AU LIPKOWITZ, S GOBEL, V VARTERASIAN, ML NAKAHARA, K TCHORZ, K KIRSCH, IR AF LIPKOWITZ, S GOBEL, V VARTERASIAN, ML NAKAHARA, K TCHORZ, K KIRSCH, IR TI A COMPARATIVE STRUCTURAL CHARACTERIZATION OF THE HUMAN NSCL-1 AND NSCL-2 GENES - 2 BASIC HELIX-LOOP-HELIX GENES EXPRESSED IN THE DEVELOPING NERVOUS-SYSTEM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEINS; MESSENGER-RNA; DROSOPHILA-MELANOGASTER; NEGATIVE REGULATOR; ENHANCER-BINDING; POINT MUTATIONS; N-MYC; SEQUENCE; ACHAETE; COMPLEX AB Human cDNA clones for NSCL-1 and NSCL-2, two basic domain helix-loop-helix (bHLH) genes expressed predominantly in the developing nervous system, were obtained from a fetal brain cDNA library. The full-length transcripts and the genomic structures were determined. The cDNAs for the two genes encode predicted proteins of similar size (133 and 135 amino acids for NSCL-1 and NSCL-2, respectively) and structure. The carboxyl-terminal 75 amino acids of the two proteins contain the bHLH motif and differ from each other by only three conservative amino acid changes, while the amino-terminal portions are markedly divergent from each other. In addition to the similar protein structure, the genes have a similar genomic organization, suggesting a close evolutionary relationship. The 5'-regulatory regions of the two genes share some features (i.e. potential TATA, CCAAT, and GATA binding sites) but also differ significantly in their G+C content. NSCL-1 is relatively G+C-rich (63%) in the sequences upstream of transcription initiation and has multiple potential binding sites for transcription factors that bind to G+C-rich sequences (e.g. AP-2). NSCL-2 is relatively A+T-rich (63%) in this region and has a potential binding site for AP1. Studies of expression in normal tissues demonstrated expression of NSCL-1 and NSCL-2 in the developing central and peripheral nervous system, most likely in developing neurons. Additional Northern analysis studies in cell lines revealed expression of these genes in some cell lines derived from tumors with neural or neuroendocrine features such as neuroblastoma, PNET, and small cell lung cancer. NSCL-1 is expressed in a larger number of these cell lines. The differences in expression may parallel differences in developmental regulation. RP LIPKOWITZ, S (reprint author), NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20892, USA. NR 50 TC 51 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1992 VL 267 IS 29 BP 21065 EP 21071 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800087 PM 1328219 ER PT J AU PORRAS, A NEBREDA, AR BENITO, M SANTOS, E AF PORRAS, A NEBREDA, AR BENITO, M SANTOS, E TI ACTIVATION OF RAS BY INSULIN IN 3T3-L1 CELLS DOES NOT INVOLVE GTPASE-ACTIVATING PROTEIN-PHOSPHORYLATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; TRK PROTOONCOGENE PRODUCT; SERINE THREONINE KINASES; SIGNAL-TRANSDUCTION; TYROSINE KINASE; PC12 CELLS; P21RAS ACTIVATION; GENE-EXPRESSION; XENOPUS OOCYTES; MAP KINASES AB Insulin-induced differentiation of 3T3 L1 cells to adipocytes can be mimicked by the expression of transfected ras oncogenes but not of the tyrosine-kinase oncogenes src and trk. Expression of two different transfected, dominant inhibitory ras mutants resulted in significant inhibition of insulin-induced differentiation, suggesting that endogenous Ras proteins are mediators of insulin signaling in these cells. Exposure of untransfected 3T3 L1 cells to insulin resulted in significant formation of the active Ras.GTP complex, at levels comparable with those resulting from exposure to platelet-derived growth factor. However, whereas exposure of the same cells to platelet-derived growth factor resulted in significant tyrosine phosphorylation of the p21ras GTPase-activating protein (GAP), insulin-treated cells did not show any detectable levels of de novo GAP tyrosine phosphorylation. Interestingly, insulin caused tyrosine phosphorylation of the p62 polypeptide coprecipitated with GAP by anti-GAP antibodies. Insulin-induced activation of cytosolic MAP kinase activity in untransfected 3T3 L1 cells was also mimicked by Ras expression (in the absence of insulin) in the same cells transfected with an inducible ras construct. These results confirm that Ras proteins participate in insulin signaling pathways in these mammalian cells and indicate that activation of cytosolic MAP kinases is an early event occurring downstream from Ras activation. However, tyrosine phosphorylation of GAP appears not to be a significant upstream regulatory event in the activation of Ras by insulin. C1 NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,RM 1D28,BETHESDA,MD 20892. RI Porras, Almudena/N-2121-2015 OI Porras, Almudena/0000-0002-6495-3308 NR 66 TC 79 Z9 79 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1992 VL 267 IS 29 BP 21124 EP 21131 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT978 UT WOS:A1992JT97800095 PM 1328223 ER PT J AU LUTY, BA MCCAMMON, JA ZHOU, HX AF LUTY, BA MCCAMMON, JA ZHOU, HX TI DIFFUSIVE REACTION-RATES FROM BROWNIAN DYNAMICS SIMULATIONS - REPLACING THE OUTER CUTOFF SURFACE BY AN ANALYTICAL TREATMENT SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID KINETICS AB The algorithm of Northrup, Allison, and McCammon V. Chem. Phys. 80, 1517 (1984)] for calculating diffusive reaction rates using Brownian dynamics simulations is reexamined. A new method is described in which a time-consuming portion of the algorithm is replaced by an analytical solution. When applied to two illustrative model systems, the new method is found to reduce the computational work by a factor of 2 or more. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RP LUTY, BA (reprint author), UNIV HOUSTON,DEPT CHEM,HOUSTON,TX 77204, USA. RI Zhou, Huan-Xiang/M-5170-2016 OI Zhou, Huan-Xiang/0000-0001-9020-0302 NR 14 TC 58 Z9 58 U1 0 U2 6 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 OCT 15 PY 1992 VL 97 IS 8 BP 5682 EP 5686 DI 10.1063/1.463777 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA JU516 UT WOS:A1992JU51600044 ER PT J AU GUMLEY, TP MCKENZIE, IFC KOZAK, CA SANDRIN, MS AF GUMLEY, TP MCKENZIE, IFC KOZAK, CA SANDRIN, MS TI ISOLATION AND CHARACTERIZATION OF CDNA CLONES FOR THE MOUSE THYMOCYTE B-CELL ANTIGEN (THB) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LY-6; ALLOANTIGENS; ASSOCIATION; EXPRESSION; RECEPTOR; COMPLEX; RNA AB The Thb locus is responsible for the expression of 15-kDa phosphatidyl inositol anchored molecules (ThB) on murine thymocytes and B cells. Thb expression as detected with mAb is polymorphic on B cells with two alleles, Thb(h) and Thb(l) responsible for the high and low expression of ThB on B cells. The regulatory locus for Thb expression had been mapped with the Ly-6 cluster of genes to Chr 15. In our study we used expression cloning in COS cells to isolate cDNA clones that code for ThB after transfection; the cDNA products react with anti- ThB antibodies, but not with Ly-6A.2, -6B.2, -6C.2, or -6D.2 antibodies. One of these clones, pThB-A contains insert of 702 bases which was sequenced. The translated amino acid sequence has 11 cysteine residues, and together with the absence of potential N-linked glycosylation sites is similar to the structure of the Ly-6 molecules. The nucleotide and amino acid sequences of ThB cDNA were compared to those of Ly-6 genes and the Ly-6 related human CD59 and show clear homology. Finally using interspecies crosses, the structural Thb gene has been mapped to Chr 15; thus both structural and regulatory genes map to a similar site. The genetic map location near Ly-6 and the sequence similarity suggest that Thb and Ly-6 may have been derived from the same progenitor by gene duplication. C1 AUSTIN HOSP,AUSTIN RES INST,MOLEC IMMUNOGENET LAB,KRONHEIMER BLDG,HEIDELBERG,VIC 3084,AUSTRALIA. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 30 TC 37 Z9 38 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 OCT 15 PY 1992 VL 149 IS 8 BP 2615 EP 2618 PG 4 WC Immunology SC Immunology GA JT982 UT WOS:A1992JT98200011 PM 1401899 ER PT J AU KREITMAN, RJ SCHNEIDER, WP QUEEN, C TSUDO, M FITZGERALD, DJP WALDMANN, TA PASTAN, I AF KREITMAN, RJ SCHNEIDER, WP QUEEN, C TSUDO, M FITZGERALD, DJP WALDMANN, TA PASTAN, I TI MIK-BETA-1(FV)-PE40, A RECOMBINANT IMMUNOTOXIN CYTOTOXIC TOWARD CELLS BEARING THE BETA-CHAIN OF THE IL-2 RECEPTOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-2 RECEPTOR; PSEUDOMONAS EXOTOXIN; CHIMERIC TOXINS; PROTEIN; EXPRESSION; DISTINCT; ANTIGEN; DOMAINS; COMPLEX AB Mik-beta1 is a mAb that binds to the beta subunit of the IL-2R. We have constructed a recombinant single chain immunotoxin Mik-beta1(Fv)-PE40 by genetically fusing the H and L V domains of Mik-beta1 to each other via a peptide linker, and then to PE40, a derivative of Pseudomonas exotoxin. Mik-beta1(Fv)-PE40 was selectively cytotoxic for cells expressing high levels of IL-2R beta (p75) subunit. Mik-beta1(Fv)-PE40 was cytotoxic to the NK cell line YT-S, which expresses p75 but not p55 subunits, with an IC50 of 6 ng/ml. The ATL line HUT-102 was less sensitive, with an IC50 of 200 ng/ml. However, the IC50 could be lowered to 11 ng/ml when Mik-beta1(Fv)-PE40 was allowed to bind to HUT-102 cells at 4-degrees-C for 4 h before overnight incubation at 37-degrees-C. An excess of Mik-beta1 but not of anti-Tac, the anti-p55 mAb, prevented the cytotoxicity of Mik-beta1(Fv)-PE40. We constructed a more active version of Mik-beta1(Fv)-PE40, designated Mik-beta1 (Fv)-PE40KDEL, by converting the carboxyl-terminus of the toxin from -REDLK to -KDEL. Mik-beta1 (Fv)-PE40KDEL showed an IC50 of 2 ng/ml toward YT-S cells and 35 ng/ml toward HUT-102 cells. Binding studies using radioiodinated Mik-beta1 showed that Mik-beta1(Fv)-PE40 bound to the p75 receptor subunit with 11% of the affinity of the native Mik-beta1 antibody. Mik-beta1(Fv)-PE40 may be a useful reagent to study cells that express IL-2R, and it deserves further study as a possible treatment for cancers in which the malignant cells express high numbers of p75 subunit. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,37-4E16,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,METAB BRANCH,BETHESDA,MD 20892. PROT DESIGN LABS,MT VIEW,CA 94043. TOKYO METROPOLITAN INST MED SCI,DEPT IMMUNOL,BUNKYO KU,TOKYO 113,JAPAN. NR 25 TC 28 Z9 29 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1992 VL 149 IS 8 BP 2810 EP 2815 PG 6 WC Immunology SC Immunology GA JT982 UT WOS:A1992JT98200038 PM 1401913 ER PT J AU ZHU, G BAX, A AF ZHU, G BAX, A TI IMPROVED LINEAR PREDICTION OF DAMPED NMR SIGNALS USING MODIFIED FORWARD BACKWARD LINEAR PREDICTION SO JOURNAL OF MAGNETIC RESONANCE LA English DT Note ID EXTRAPOLATION; RESOLUTION; TRANSFORM C1 UNIV MARYLAND,CHEM PHYS PROGRAM,COLL PK,MD 20742. RP ZHU, G (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 10 TC 91 Z9 91 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD OCT 15 PY 1992 VL 100 IS 1 BP 202 EP 207 DI 10.1016/0022-2364(92)90379-L PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA JW476 UT WOS:A1992JW47600019 ER PT J AU VUISTER, GW RUIZCABELLO, J VANZIJL, PCM AF VUISTER, GW RUIZCABELLO, J VANZIJL, PCM TI GRADIENT-ENHANCED MULTIPLE-QUANTUM FILTER (GE-MQF) - A SIMPLE WAY TO OBTAIN SINGLE-SCAN PHASE-SENSITIVE HMQC SPECTRA SO JOURNAL OF MAGNETIC RESONANCE LA English DT Note ID PULSED FIELD GRADIENTS; NMR-SPECTRA; CHEMICAL-SHIFTS; SPECTROSCOPY; PROTON; COHERENCE; N-15; PROTEINS; COSY C1 GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,ROCKVILLE,MD 20850. RP VUISTER, GW (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI van Zijl, Peter/B-8680-2008; OI Ruiz-Cabello, Jesus/0000-0001-8681-5056 NR 24 TC 29 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 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD OCT 15 PY 1992 VL 100 IS 1 BP 215 EP 220 DI 10.1016/0022-2364(92)90381-G PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA JW476 UT WOS:A1992JW47600021 ER PT J AU SILVERMAN, K EVANS, SM STRAIN, EC GRIFFITHS, RR AF SILVERMAN, K EVANS, SM STRAIN, EC GRIFFITHS, RR TI WITHDRAWAL SYNDROME AFTER THE DOUBLE-BLIND CESSATION OF CAFFEINE CONSUMPTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PHYSICAL-DEPENDENCE; VERSION; HUMANS AB Background. People who stop consuming caffeine may have symptoms, but the incidence and severity of caffeine withdrawal are not known. This study was performed to determine the effects in the general population of ending one's dietary intake of caffeine. Methods. We studied 62 normal adults whose intake of caffeine was low to moderate (mean amount, 235 mg - the equivalent of 2.5 cups of coffee - per day). They completed questionnaires about symptoms and tests of their mood and performance when consuming their normal diets (base-line period) and at the end of each of two two-day periods during which they consumed caffeine-free diets and under double-blind conditions received capsules containing placebo (placebo period) or caffeine (caffeine period) in amounts equal to their daily caffeine consumption. Results. More subjects had abnormally high Beck Depression inventory scores (11 percent), high scores on the trait scale of the State-Trait Anxiety Inventory (8 percent), low vigor scores (11 percent) and high fatigue scores (8 percent) on the Profile of Mood States, and moderate or severe headache (52 percent) during the placebo period than during either the base-line period (2, 0, 0, 0, and 2 percent, respectively; P<0.05) or the caffeine period (3, 2, 2, 0, and 6 percent; P<0.05). More subjects reported unauthorized use of medications during the placebo period (13 percent) than during the caffeine period (2 percent, P = 0.017). Performance of a tapping task was slower during the placebo period than during the base-line and caffeine periods (P<0.01). Conclusions. Persons who consume low or moderate amounts of caffeine may have a withdrawal syndrome after their daily consumption of caffeine ceases. C1 JOHNS HOPKINS UNIV,SCH MED,BEHAV BIOL RES CTR,DEPT PSYCHIAT & BEHAV SCI,5510 NATHAN SHOCK DR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,LEXINGTON,KY 40583. OI Silverman, Kenneth/0000-0003-2724-1413 FU NIDA NIH HHS [R01 DA03890] NR 26 TC 244 Z9 249 U1 4 U2 21 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 15 PY 1992 VL 327 IS 16 BP 1109 EP 1114 DI 10.1056/NEJM199210153271601 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JT153 UT WOS:A1992JT15300001 PM 1528206 ER PT J AU MASOLIVER, J PORRA, J WEISS, GH AF MASOLIVER, J PORRA, J WEISS, GH TI SOLUTIONS OF THE TELEGRAPHERS EQUATION IN THE PRESENCE OF TRAPS - REPLY SO PHYSICAL REVIEW A LA English DT Letter AB This reply adds a number of details to remarks by Foong and Kanno [preceding Comment, Phys. Rev. A 46, 5296 (1992)] on our paper [Phys. Rev. A 45, 2222 (1992)] regarding the discontinuities observed in the curves generated in that paper. C1 NIH,BETHESDA,MD 20892. RP MASOLIVER, J (reprint author), UNIV BARCELONA,DEPT FIS FONAMENTAL,E-08027 BARCELONA,SPAIN. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD OCT 15 PY 1992 VL 46 IS 8 BP 5298 EP 5298 DI 10.1103/PhysRevA.46.5298 PG 1 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA JW974 UT WOS:A1992JW97400115 ER PT J AU KOSUGI, A WEISSMAN, AM OGATA, M HAMAOKA, T FUJIWARA, H AF KOSUGI, A WEISSMAN, AM OGATA, M HAMAOKA, T FUJIWARA, H TI INSTABILITY OF ASSEMBLED T-CELL RECEPTOR COMPLEX THAT IS ASSOCIATED WITH RAPID DEGRADATION OF ZETA CHAINS IN IMMATURE CD4+CD8+ THYMOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T-CELL DEVELOPMENT; T-CELL RECEPTOR ASSEMBLY; THYMIC SELECTION ID PRE-GOLGI DEGRADATION; ANTIGEN RECEPTOR; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; EXPRESSION; PROTEIN; BIOLOGY; EVENTS; THYMUS AB The intracellular fate of newly synthesized T-cell receptor (TCR) chains was compared in CD4+CD8+ (double positive; DP) thymocytes and in CD4+CD8- or CD4-CD8+ (single positive; SP) thymocytes. Purified DP and SP thymocytes from normal adult mice were analyzed by pulse-chase metabolic labeling and immunoprecipitation with specific anti-TCR antibodies. Biosynthesis of invariant chains (CD3gamma, -delta, -epsilon, and zeta) was comparable between DP and SP thymocytes, whereas DP thymocytes synthesized TCR alpha and TCR beta chains at lower and higher levels than SP thymocytes, respectively. These newly synthesized TCR chains were degraded at different rates in SP thymocytes based on their sensitivities for degradation as previously reported: TCR alpha, TCR beta, CD3gamma, and CD3delta chains were rapidly degraded and CD3epsilon and zeta chains were stable. Although the degradation rates of clonotypic and invariant CD3 chains were similar in DP and SP thymocytes, the zeta subunit was rapidly degraded in DP thymocytes (t1/2, almost-equal-to 1.5 hr). Degradation of zeta was inhibited by NH4Cl, implicating lysosomes as the site of degradation. Comparison of TCR subunit assembly in DP and SP thymocytes demonstrated that, despite the same relative rate of formation of TCR complexes in a pulse period (30 min), complete complexes were unstable and degraded during the subsequent 6 hr of chase in DP thymocytes. This contrasted with the stability and a progressive increase in the levels of completely assembled complexes in SP thymocytes. Thus, these results demonstrate that a unique posttranslational regulation operates in the formation of TCR complexes in DP thymocytes and that lack of stability of complete TCR complexes is a crucial mechanism that may account for the limited surface TCR expression on this thymocyte subset. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP KOSUGI, A (reprint author), OSAKA UNIV,SCH MED,BIOMED RES CTR,2-2 YAMADAOKA,SUITA,OSAKA 565,JAPAN. NR 26 TC 20 Z9 20 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 OCT 15 PY 1992 VL 89 IS 20 BP 9494 EP 9498 DI 10.1073/pnas.89.20.9494 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700027 PM 1357664 ER PT J AU RIBEIRO, P WANG, YH CITRON, BA KAUFMAN, S AF RIBEIRO, P WANG, YH CITRON, BA KAUFMAN, S TI REGULATION OF RECOMBINANT RAT TYROSINE-HYDROXYLASE BY DOPAMINE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BOVINE ADRENAL-MEDULLA; ESCHERICHIA-COLI; PROTEIN-KINASE; 3-MONOOXYGENASE; PURIFICATION; BINDING; IRON; PHOSPHORYLATION; EXPRESSION; ENZYME AB Recombinant rat PC12 tyrosine hydroxylase, also called tyrosine 3-monooxygenase [L-tyrosine, tetrahydropteridine:oxygen oxidoreductase (3-hydroxylating), EC 1.14.16.2], purified from Escherichia coli is in an activated form with a low K(m) for the tetrahydrobiopterin cofactor and a pH optimum of 6.5. Pretreatment with low levels of the derived product, dopamine, inhibits catalytic activity, increases the K(m) for the cofactor, and shifts the pH curve towards a more acidic pH optimum. Labeled dopamine binds to tyrosine hydroxylase with high affinity (K(d) = 1 muM) but low stoichiometry (r = 0.08 mol/mol of enzyme subunit). The binding of dopamine results in the appearance of a blue-green chromophore with lambda(max) at almost-equal-to 660 nm, which is consistent with the formation of a catecholamine-iron complex. In the absence of dopamine, the recombinant enzyme cannot be further activated by phosphorylation with cAMP-dependent protein kinase, although as much as 1 mol of phosphate is incorporated per mol of subunit. In contrast, the enzyme pretreated with dopamine is activated by phosphorylation in the same fashion and to the same extent as the native hydroxylase. The results suggest that the high-affinity binding of catecholamine products is a pivotal posttranslational modification that determines the state of enzyme activation and the response to phosphorylation. RP RIBEIRO, P (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 24 TC 38 Z9 38 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 OCT 15 PY 1992 VL 89 IS 20 BP 9593 EP 9597 DI 10.1073/pnas.89.20.9593 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700047 PM 1357665 ER PT J AU BURGIN, AB NASH, HA AF BURGIN, AB NASH, HA TI SYMMETRY IN THE MECHANISM OF BACTERIOPHAGE-LAMBDA INTEGRATIVE RECOMBINATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SITE-SPECIFIC RECOMBINATION; DNA STRAND EXCHANGE; DNA TOPOISOMERASE ID SITE-SPECIFIC RECOMBINATION; STRAND TRANSFER; DNA; HOMOLOGY; PROTEIN; CLEAVAGE; SYNAPSIS; STEP AB During the strand-exchange events of bacteriophage lambda integration, pairs of phosphodiester bonds are broken and then rejoined to form novel DNA linkages. The reaction proceeds in vitro in the absence of an external energy source; the bond energy needed to rejoin broken strands of DNA must therefore be conserved during cleavage. Although some of this conservation involves a covalent intermediate between DNA and the recombinase Int, it is possible that such an intermediate is formed with only one of the two phosphodiesters. In such an asymmetric mechanism, the second phosphodiester would be attacked by a nucleophile that is exposed by cleavage of the first DNA strand. In contrast, a symmetric mechanism hypothesizes nucleophilic attack by Int on both phosphodiesters. We have distinguished these two mechanisms by removing potential nucleophiles from the integrative recombination reaction. Our data are inconsistent with an asymmetric mechanism. We conclude that during strand exchange both phosphodiesters proceed through a covalent protein-DNA intermediate. RP BURGIN, AB (reprint author), NIMH,BLDG 36,ROOM 1B-08,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 20 Z9 20 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 OCT 15 PY 1992 VL 89 IS 20 BP 9642 EP 9646 DI 10.1073/pnas.89.20.9642 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700057 PM 1409677 ER PT J AU KARP, DR JENKINS, RN LONG, EO AF KARP, DR JENKINS, RN LONG, EO TI DISTINCT BINDING-SITES ON HLA-DR FOR INVARIANT CHAIN AND STAPHYLOCOCCAL ENTEROTOXINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MAJOR HISTOCOMPATIBILITY COMPLEX; SUPERANTIGENS ID CLASS-II MOLECULES; T-CELLS; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; SURFACE EXPRESSION; PEPTIDE BINDING; CLONAL DELETION; SUPERANTIGENS; ASSOCIATION; TRANSPORT AB During biosynthesis, class II molecules of the major histocompatibility complex exist as complexes of the polymorphic alpha and beta chains in association with trimers of the invariant chain (Ii). The nonpolymorphic Ii contains sequences necessary for proper targeting of class II to endosomal compartments, where Ii is degraded. Ii also prevents the premature association of antigenic peptides with class II molecules. It is not known whether the effect of Ii on peptide binding extends to other ligands of class II, specifically exogenous superantigens. Cells expressing a mutant Ii molecule stably associated with HLA-DR at the cell surface were tested for their ability to interact with staphylococcal toxins. Most toxins (staphylococcal enterotoxins A-E and exfoliative toxin) were found to bind to cells expressing this alphabetaIi complex with levels comparable to cells expressing only alphabeta chains at the cell surface. Cells expressing surface alphabetaIi complexes stimulated polyclonal populations of peripheral blood T cells in association with these toxins. Binding of toxic shock syndrome toxin (TSST) and subsequent stimulation of T cells were reduced by the presence of the Ii. This reduction was not due to an alteration in the repertoire of T cells responding to TSST in the presence of Ii. Data from experiments with a T-cell clone suggest that interactions between class II molecules and T-cell antigen receptors occur during staphylococcal enterotoxin-mediated stimulation and that surface Ii does not interfere with such interactions. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. RP KARP, DR (reprint author), UNIV TEXAS,SW MED CTR,SIMMONS ARTHRIT RES CTR,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 36 TC 21 Z9 22 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 OCT 15 PY 1992 VL 89 IS 20 BP 9657 EP 9661 DI 10.1073/pnas.89.20.9657 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700060 PM 1409679 ER PT J AU PODDA, S WARD, M HIMELSTEIN, A RICHARDSON, C DELAFLORWEISS, E SMITH, L GOTTESMAN, M PASTAN, I BANK, A AF PODDA, S WARD, M HIMELSTEIN, A RICHARDSON, C DELAFLORWEISS, E SMITH, L GOTTESMAN, M PASTAN, I BANK, A TI TRANSFER AND EXPRESSION OF THE HUMAN MULTIPLE-DRUG RESISTANCE GENE INTO LIVE MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BONE MARROW TRANSPLANTATION; GENE THERAPY ID HEMATOPOIETIC STEM-CELLS; BETA-GLOBIN GENE; MULTIDRUG RESISTANCE; BONE-MARROW; MAMMALIAN-CELLS; PACKAGING LINE; RETROVIRUS; MDR1 AB The human multiple drug resistance (MDR) gene has been used as a selectable marker to increase the proportion of bone marrow cells that contain and express this gene by drug selection. By constructing retroviral vectors containing and expressing the MDR gene and a nonselectable gene such as the beta-globin gene, enrichment for cells containing both of these genes can be achieved. A retroviral construct containing MDR cDNA in a Harvey virus-based vector has been used to transfect our ecotropic 3T3 retroviral packaging line GP+E86. Clones have been isolated by exposure of the retrovirally transfected cells (MDR producer cells) to colchicine (60 ng/ml), a selective agent that kills MDR-negative cells. Flow cytometry analysis (fluorescence-activated cell sorting) with an antibody to MDR demonstrates expression of human MDR protein on the surface of these colchicine-resistant producer clones. Untransfected GP + E86 cells are negative. Colchicine-resistant clones were titered using clone supernatants and the highest titer clone (4 x 10(4) viral particles per ml) was cocultured with 10(6) donor mouse bone marrow cells for 24-48 hr. The donor cells were then injected into congenic irradiated mice, and the presence of the MDR gene was assayed by the polymerase chain reaction (PCR) analysis using MDR-specific primers. In one experiment eight of nine transduced mice were positive for MDR by PCR of peripheral blood 14 and 50 days posttransplantation; after 240 days three of nine transduced mice were positive. Bone marrow obtained from one of these positive animals was stained with the MDR monoclonal antibody and the granulocyte population was analyzed by FACS. Approximately 14% of the total granulocyte pool contain increased levels of MDR protein. In addition, the bone marrow cells of several mice initially positive for MDR gene by PCR, and subsequently negative, were exposed to taxol, a drug whose detoxification depends on MDR gene expression; a positive signal was obtained in all of these mice, indicating drug selection of MDR-positive marrow cells. Cell sorting studies of these mice also show an increased number of high-MDR-expressing marrow cells, selected after exposure to taxol. Thus, in this live animal model MDR transduction is effective in selecting a human MDR-expressing population of marrow cells resistant to taxol chemotherapy. This strategy may, thus, be useful in humans to prevent the marrow toxicity induced by anticancer agents such as taxol and as a selectable marker to enrich for cells simultaneously transduced with a nonselectable gene. C1 NCI,DIV CANC BIOL & DIAGN,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL & DIAGN,CELL BIOL LAB,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,DEPT GENET & DEV,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. FU NHLBI NIH HHS [HL-28381]; NIDDK NIH HHS [DK-07373] NR 24 TC 214 Z9 217 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 OCT 15 PY 1992 VL 89 IS 20 BP 9676 EP 9680 DI 10.1073/pnas.89.20.9676 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700064 PM 1357667 ER PT J AU KIM, J ADHYA, S GARGES, S AF KIM, J ADHYA, S GARGES, S TI ALLOSTERIC CHANGES IN THE CAMP RECEPTOR PROTEIN OF ESCHERICHIA-COLI - HINGE REORIENTATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROTEIN CONFORMATION; DNA-PROTEIN INTERACTION; GENE REGULATION ID ADENOSINE-MONOPHOSPHATE RECEPTOR; GENE ACTIVATOR PROTEIN; CYCLIC-AMP; DNA-BINDING; CONFORMATIONAL TRANSITIONS; TRYPTOPHAN SYNTHASE; COMPLEX; CONSTRUCTION; RESOLUTION; MUTATIONS AB The cAMP receptor protein (CRP) of Escherichia coli is a dimer of a two-domain subunit. It requires binding of cAMP for a conformational change in order to function as a site-specific DNA-binding protein that regulates gene activity. The hinge region connecting the cAMP-binding domain to the DNA-binding domain is involved in the cAMP-induced allosteric change. We studied the structural changes in CRP that are required for gene regulation by making a large number of single and double amino acid substitutions at four different positions in or near the hinge. To achieve cAMP-independent transcription by CRP, amino acid residues 138 (located within the hinge region) and 141 (located in the D alpha-helix adjacent to the hinge) must be polar. This need for polar residues at positions 138 and 141 suggests an interaction that causes the C and D alpha-helices to come together. As a consequence, the F alpha-helix is released from the D alpha-helix and can interact with DNA. At position 144 in the D alpha-helix and within interacting distances of the F alpha-helix, replacement of alanine by an amino acid with a larger side chain, regardless of its nature, allows cAMP independence. This result indicates that pushing against the F alpha-helix may be a way of making the helix available for DNA binding. We believe that the cAMP-induced allosteric change involves similar hinge reorientation to adjust the C and D alpha-helices, allowing outward movement of the F alpha-helix. C1 NCI,MICROBIOL LAB,BETHESDA,MD 20892. NR 36 TC 74 Z9 74 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 OCT 15 PY 1992 VL 89 IS 20 BP 9700 EP 9704 DI 10.1073/pnas.89.20.9700 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700069 PM 1409686 ER PT J AU JANCZEWSKI, DN YUHKI, N GILBERT, DA JEFFERSON, GT OBRIEN, SJ AF JANCZEWSKI, DN YUHKI, N GILBERT, DA JEFFERSON, GT OBRIEN, SJ TI MOLECULAR PHYLOGENETIC INFERENCE FROM SABER-TOOTHED CAT FOSSILS OF RANCHO-LA-BREA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLYMERASE CHAIN-REACTION; CLASS-I GENES; MITOCHONDRIAL-DNA; ENZYMATIC AMPLIFICATION; DIVERSITY; SEQUENCE; EVOLUTION; DIVERGENCE; DISTANCE; CLONING AB A method for the successful extraction of sequestered cellular DNA from 14,000-year-old fossil bones was developed and applied to asphalt-preserved specimens of the extinct saber-toothed cat, Smilodon fatalis. Two distinct gene segments, the mitochondrial gene for 12S rRNA and nuclear FLA-I (the feline class I major histocompatibility complex gene), from three different individual fossil specimens were cloned and sequenced after PCR amplification. Comparison of fossil-derived DNA sequences to homologous regions in 15 living carnivorous species, including 9 species of Felidae and 6 nonfelids, affirmed the phylogenetic placement of Smilodon within the modern radiation of Felidae distinct from the Miocene paleofelid (Nimravidae) saber-toothed "cat" species. These results raise the prospect of obtaining genetically informative DNA from preserved bones of extinct fossil species, particularly among the 2 million specimens excavated from the asphaltic sediments at Rancho La Brea in metropolitan Los Angeles. C1 NCI, FREDERICK CANC RES & DEV CTR, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NAT HIST MUSEUM LOS ANGELES, GEORGE C PAGE MUSEUM, LOS ANGELES, CA 90036 USA. NR 58 TC 50 Z9 52 U1 0 U2 8 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 OCT 15 PY 1992 VL 89 IS 20 BP 9769 EP 9773 DI 10.1073/pnas.89.20.9769 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700083 PM 1409696 ER PT J AU LOVE, PE TREMBLAY, ML WESTPHAL, H AF LOVE, PE TREMBLAY, ML WESTPHAL, H TI TARGETING OF THE T-CELL RECEPTOR ZETA-CHAIN GENE IN EMBRYONIC STEM-CELLS - STRATEGIES FOR GENERATING MULTIPLE MUTATIONS IN A SINGLE GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENE TARGETING; HOMOLOGOUS RECOMBINATION ID GERM-LINE TRANSMISSION; NATURAL-KILLER CELLS; HOMOLOGOUS RECOMBINATION; ANTIGEN RECEPTOR; INT-1 PROTOONCOGENE; MAMMALIAN-CELLS; HPRT GENE; IGG FC; MICE; DISRUPTION AB The T-cell receptor zeta chain is a member of a family of related proteins that play a critical role in coupling cell-surface receptors to intracellular signaling pathways. To study the role of zeta chain in T-cell ontogeny, we generated targeted mutations of the zeta-chain gene in murine embryonic stem cells. The mutant alleles are predicted to result either in a null phenotype or in the synthesis of a truncated protein capable of supporting T-cell-receptor surface expression but deficient in transmembrane signaling. Both of these targeting events were recovered in a single electroporation experiment with either coelectroporation or a combination deletion/truncation construct. Our results suggest that similar approaches could be used to generate multiple single mutations, modifications of more than one site within a gene, or subtle alterations that rely upon coconversion with the selectable marker gene. RP LOVE, PE (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BLDG 6B,BETHESDA,MD 20892, USA. NR 40 TC 16 Z9 16 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 OCT 15 PY 1992 VL 89 IS 20 BP 9929 EP 9933 DI 10.1073/pnas.89.20.9929 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JT977 UT WOS:A1992JT97700116 PM 1409721 ER PT J AU MOORE, J CAMPANA, J LAM, M SANDAUCHRISTOPHER, D SADLER, J SCALISE, D GAY, N STALVEY, R SCHROEDER, J PELTON, J BIEHR, BJ HARRIS, J STRUNK, N CHIOTTI, R OWENSNAUSLER, J GRENERT, B CHIODA, D COLE, D MEURER, K ABELSON, G SHEFFIELD, A RUZICKA, P BALSLEY, C SUTTER, M CHERNECO, MD FRASER, J CARR, M WORD, E SIMPSON, P LACY, L TYE, S NEHLSLOWE, B ANDERSON, B AF MOORE, J CAMPANA, J LAM, M SANDAUCHRISTOPHER, D SADLER, J SCALISE, D GAY, N STALVEY, R SCHROEDER, J PELTON, J BIEHR, BJ HARRIS, J STRUNK, N CHIOTTI, R OWENSNAUSLER, J GRENERT, B CHIODA, D COLE, D MEURER, K ABELSON, G SHEFFIELD, A RUZICKA, P BALSLEY, C SUTTER, M CHERNECO, MD FRASER, J CARR, M WORD, E SIMPSON, P LACY, L TYE, S NEHLSLOWE, B ANDERSON, B TI TOBACCO, ALCOHOL, AND OTHER DRUG-USE AMONG HIGH-SCHOOL STUDENTS-UNITED STATES, 1991 (REPRINTED FROM MMWR, VOL 41, PG 698-703, 1992) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 SAN DIEGO UNIFIED SCH DIST,SAN DIEGO,CA. SAN FRANCISCO UNIFIED SCH DIST,SAN FRANCISCO,CA. DIST COLUMBIA PUBL SCH,WASHINGTON,DC. CHICAGO PUBL SCH,CHICAGO,IL. BOSTON PUBL SCH SYST,BOSTON,MA. NEW YORK CITY BOARD EDUC,NEW YORK,NY. SCH DIST PHILADELPHIA,PHILADELPHIA,PA. DALLAS INDEPENDENT SCH DIST,DALLAS,TX. NEW YORK STATE DEPT EDUC,ALBANY,NY 12224. NIDA,LEXINGTON,KY 40583. CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,DIV ADOLESCENT & SCH HLTH,ATLANTA,GA 30333. CTR DIS CONTROL,OFF SMOKING & HLTH,MENTAL HLTH ADM,ATLANTA,GA 30333. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 14 PY 1992 VL 268 IS 14 BP 1841 EP 1842 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JR439 UT WOS:A1992JR43900018 ER PT J AU HAVERKOS, HW BATTJES, RJ AF HAVERKOS, HW BATTJES, RJ TI FEMALE-TO-MALE TRANSMISSION OF HIV SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; HETEROSEXUAL PARTNERS; ADULTS RP HAVERKOS, HW (reprint author), NIDA,ROCKVILLE,MD, USA. NR 8 TC 16 Z9 16 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 14 PY 1992 VL 268 IS 14 BP 1855 EP 1855 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JR439 UT WOS:A1992JR43900019 PM 1404705 ER PT J AU AMOS, CI SHAW, GL TUCKER, MA HARTGE, P AF AMOS, CI SHAW, GL TUCKER, MA HARTGE, P TI AGE AT ONSET FOR FAMILIAL EPITHELIAL OVARIAN-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PROPHYLACTIC OOPHORECTOMY; BREAST; CARCINOMA; LINKAGE; PRONE AB Objective.-To provide age-specific risks for ovarian cancer for relatives of ovarian cancer case patients. To characterize the age at onset for ovarian cancer for women with a single relative vs several relatives affected with ovarian cancer. Design.-Three previous studies were reexamined. The cumulative probability of ovarian cancer in first-degree relatives of women with histologically confirmed epithelial ovarian cancer and matched control subjects who participated in the Cancer and Steroid Hormone (CASH) Study was determined. The age of onset of ovarian cancer in women with and without relatives with ovarian cancer in a Washington, DC, case-control study was contrasted with that of women with at least two first-degree relatives studied at the National Cancer Institute (NCI). Results.-The CASH Study data showed that first-degree relatives of women with ovarian cancer had an increased risk for ovarian cancer, especially at older ages, when compared with relatives of control subjects. However, the median age at onset was the same among women in the Washington, DC, study with and without an affected relative. Among the women with an extensive family history of ovarian cancer studied at the NCI, the age at onset was considerably younger (47 years) than is typical for this disease (59 years). Of these, 17% had been diagnosed as having primary ovarian cancer by age 40 years. Conclusions.-Women who have one first-degree relative affected by ovarian cancer are at greater risk for ovarian cancer but not at an age earlier than the general population. The small proportion of women who have several affected relatives are, however, at a greater risk of early onset of ovarian cancer. Prophylactic oophorectomy may be reasonable for these women. C1 NCI,BETHESDA,MD 20892. RP AMOS, CI (reprint author), NIAMSD,LSB,GENET STUDIES SECT,BLDG 6,ROOM 249,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 FU PHS HHS [3-Y01-8-1037] NR 28 TC 54 Z9 54 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 OCT 14 PY 1992 VL 268 IS 14 BP 1896 EP 1899 DI 10.1001/jama.268.14.1896 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA JR439 UT WOS:A1992JR43900039 PM 1404714 ER PT J AU RUBINOW, DR AF RUBINOW, DR TI THE PREMENSTRUAL-SYNDROME - NEW VIEWS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PLASMA BETA-ENDORPHIN; MENSTRUAL-CYCLE; MOOD DISORDER; WOMEN; TENSION; OVARIECTOMY; DEPRESSION; RESPONSES; SYMPTOMS; PHASE C1 NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BETHESDA,MD 20892. NR 35 TC 26 Z9 27 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 OCT 14 PY 1992 VL 268 IS 14 BP 1908 EP 1912 DI 10.1001/jama.268.14.1908 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JR439 UT WOS:A1992JR43900042 PM 1404717 ER PT J AU PINN, VW AF PINN, VW TI WOMENS HEALTH RESEARCH - PRESCRIBING CHANGE AND ADDRESSING THE ISSUES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID POSTMENOPAUSAL ESTROGEN; CARDIOVASCULAR-DISEASE; NURSES HEALTH RP PINN, VW (reprint author), NIH,OFF RES WOMENS HLTH,BLDG 1,RM 201,BETHESDA,MD 20892, USA. NR 27 TC 25 Z9 25 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 14 PY 1992 VL 268 IS 14 BP 1921 EP 1922 DI 10.1001/jama.268.14.1921 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JR439 UT WOS:A1992JR43900045 PM 1404720 ER PT J AU BETENBAUGH, MJ LINDSAY, DA JUARBEOSORIO, LG GORZIGLIA, M VONDERFECHT, S EIDEN, JJ AF BETENBAUGH, MJ LINDSAY, DA JUARBEOSORIO, LG GORZIGLIA, M VONDERFECHT, S EIDEN, JJ TI GENETICALLY ENGINEERED VIRAL-ANTIGENS FROM INSECT CELL-CULTURE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID GROUP-B ROTAVIRUS; BACULOVIRUS RECOMBINANT; PROTEINS; VIRUS; HEMAGGLUTININ; EXPRESSION; VECTORS; STRAIN; GENE C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. RP BETENBAUGH, MJ (reprint author), JOHNS HOPKINS UNIV,DEPT CHEM ENGN,BALTIMORE,MD 21218, USA. RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 NR 29 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 OCT 13 PY 1992 VL 665 BP 210 EP 218 DI 10.1111/j.1749-6632.1992.tb42585.x PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JV459 UT WOS:A1992JV45900017 PM 1329599 ER PT J AU REUVENY, S KEMP, CW EPPSTEIN, L SHILOACH, J AF REUVENY, S KEMP, CW EPPSTEIN, L SHILOACH, J TI CARBOHYDRATE-METABOLISM IN INSECT CELL-CULTURES DURING CELL-GROWTH AND RECOMBINANT PROTEIN-PRODUCTION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID BACULOVIRUS C1 NIDDKD,CELLULAR & DEV BIOL LAB,BIOTECHNOL UNIT,BETHESDA,MD 20892. WHITTAKER BIOPROD INC,WALKERSVILLE,MD 21793. NEW BRUNSWICK SCI INC,EDISON,NJ 08818. NR 5 TC 22 Z9 24 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD OCT 13 PY 1992 VL 665 BP 230 EP 237 DI 10.1111/j.1749-6632.1992.tb42587.x PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JV459 UT WOS:A1992JV45900019 PM 1416605 ER PT J AU HSIAO, J AHLUWALIA, M KAUFMAN, JB CLEM, TR SHILOACH, J AF HSIAO, J AHLUWALIA, M KAUFMAN, JB CLEM, TR SHILOACH, J TI ADAPTIVE-CONTROL STRATEGY FOR MAINTAINING DISSOLVED-OXYGEN CONCENTRATION IN HIGH-DENSITY GROWTH OF RECOMBINANT ESCHERICHIA-COLI SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID ESCHERICHIA-COLI; SYSTEM; CULTURE C1 NIH,CELLULAR & DEV BIOL LAB,BIOTECHNOL UNIT,BETHESDA,MD 20892. FLUOR DANIEL INC,DEPT CONTROL SYST,GREENVILLE,SC 29607. NIH,DIV RES SERV,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 20 TC 23 Z9 23 U1 1 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD OCT 13 PY 1992 VL 665 BP 320 EP 333 DI 10.1111/j.1749-6632.1992.tb42595.x PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JV459 UT WOS:A1992JV45900027 PM 1416613 ER PT J AU BENJAMIN, DC WILLIAMS, DC SMITHGILL, SJ RULE, GS AF BENJAMIN, DC WILLIAMS, DC SMITHGILL, SJ RULE, GS TI LONG-RANGE CHANGES IN A PROTEIN ANTIGEN DUE TO ANTIGEN-ANTIBODY INTERACTION SO BIOCHEMISTRY LA English DT Article ID HORSE CYTOCHROME-C; 3-DIMENSIONAL STRUCTURE; MONOCLONAL-ANTIBODIES; LEAST-SQUARES; FAB FRAGMENT; COMPLEX; LYSOZYME; RESOLUTION; EXCHANGE; SITE AB Amide exchange kinetics were used to probe the conformation of hen egg-white lysozyme complexed with the anti-lysozyme monoclonal antibody HyHEL-5. Following the technique developed by Paterson et al. [(1990) Science 249,755-7591 we used two-dimensional NMR to measure amide exchange kinetics of the lysozyme amide protons in the lysozyme-antibody complex. A total of 15 amide protons showed altered exchange kinetics in the presence of the complex. Five of these 15 protons reside on residues that are found within the epitope as defined by X-ray crystallography. Five residues are located at the perimeter of the epitope. The remaining five residues are removed from the epitope. The perturbation of amide exchange rates at sites distant from the epitope indicates that the formation of antigen-antibody complexes can produce changes in the antigen at sites that are quite distant from the structural epitope. C1 UNIV VIRGINIA,DEPT BIOCHEM,BOX 440,JORDAN HALL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. NCI,GENET LAB,BETHESDA,MD 20892. RI Rule, Gordon/Q-2422-2015 OI Rule, Gordon/0000-0002-4396-3363 FU NCRR NIH HHS [RR-05431]; NIAID NIH HHS [AI-20745] NR 29 TC 66 Z9 66 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 13 PY 1992 VL 31 IS 40 BP 9539 EP 9545 DI 10.1021/bi00155a005 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JT518 UT WOS:A1992JT51800005 PM 1382591 ER PT J AU RODRIGUEZ, IR GONZALEZ, P ZIGLER, JS BORRAS, T AF RODRIGUEZ, IR GONZALEZ, P ZIGLER, JS BORRAS, T TI A GUINEA-PIG HEREDITARY CATARACT CONTAINS A SPLICE-SITE DELETION IN A CRYSTALLIN GENE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE CONGENITAL CATARACT; ZETA-CRYSTALLIN; RNA SPLICING; CDNA CLONING ID ZETA-CRYSTALLIN; RETINITIS-PIGMENTOSA; CONGENITAL CATARACT; RHODOPSIN GENE; LENS PROTEIN; FAMILY; MUTATION; DEHYDROGENASES; LOCUS AB A congenital cataract present in guinea pigs provided a unique opportunity to study a hereditary lens disease at the molecular level. zeta-Crystallin, one of the most abundant guinea pig lens proteins, was found to be altered in the lens of cataractous animals. Several zeta-crystallin cDNA clones were isolated from a cataractous lens library and found to contain a 102-bp deletion towards the 3' end of the coding region. This deletion does not interfere with the reading frame but results in a protein 34 amino acids shorter. Sequence analysis of a normal genomic zeta-crystallin clone revealed that the missing 102-bp fragment corresponds to an entire exon (exon 7). PCR analysis of the genomic DNA isolated from cataractous animals showed that exon 7, though missing from the mRNA, is intact in the cataractous genome. Further sequence analysis of the zeta-crystallin gene disclosed a dinucleotide deletion of the universal AG at the acceptor splice-site of intron 6 of the mutant gene. The presence of this mutation results in the skipping of exon 7 during the mRNA processing which in turn results in the altered zeta-crystallin protein. This is the first time a genomic mutation in an enzyme/crystallin gene has been directly linked to a congenital cataract. RP RODRIGUEZ, IR (reprint author), NEI,MECHANISMS OCULAR DIS LAB,BLDG 6 RM 307,BETHESDA,MD 20892, USA. NR 24 TC 50 Z9 51 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD OCT 13 PY 1992 VL 1180 IS 1 BP 44 EP 52 DI 10.1016/0925-4439(92)90025-I PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JT839 UT WOS:A1992JT83900007 PM 1390943 ER PT J AU DRAY, F VULLIEZLENORMAND, B DEROUSSENT, A BRIQUET, I GABELLEC, MM NAKAMURA, S WAHL, LM GOUYETTE, A SALAHUDDIN, ZS AF DRAY, F VULLIEZLENORMAND, B DEROUSSENT, A BRIQUET, I GABELLEC, MM NAKAMURA, S WAHL, LM GOUYETTE, A SALAHUDDIN, ZS TI ACTIVE METABOLISM OF ARACHIDONIC-ACID BY KAPOSI-SARCOMA CELLS CULTURED FROM LUNG BIOPSIES (KS-3) - IDENTIFICATION BY HPLC AND MS/MS OF THE PREDOMINANT METABOLITE SECRETED AS THE 11,12-EPOXY-EICOSATRIENOIC ACID SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE AIDS; KAPOSI SARCOMA; ARACHIDONIC ACID METABOLISM; EPOXYEICOSATRIENOIC ACID ID HUMAN-ENDOTHELIAL CELLS; LONG-TERM CULTURE; EPOXYEICOSATRIENOIC ACIDS; PROSTACYCLIN PRODUCTION; PROSTAGLANDIN; THROMBIN; LIPOXYGENASE; STIMULATION; HISTAMINE; RELEASE AB The development of long-term culture of AIDS-KS cells has allowed us to investigate further a possible vascular origin of Kaposi sarcoma. Taking into account the relative specificity of arachidonic acid (AA) metabolism according to cell type, the AA `cascade' was analyzed in cultured KS-3 cells established from lung biopsies and compared to human umbilical venous endothelial (H-UVE) cells and human myometrial smooth muscle (H-MSM) cells, under basal conditions and after stimulation with vasoactive agents such as histamine or thrombin. Considering strictly the `prostaglandin' profile given by RIAs, the metabolism of AA was closer, whilst not identical, to H-UVE than to H-MSM cells. However, evaluation of all the eicosanoids released from [H-3]AA labeled KS-3 cells revealed that the predominant metabolite was not prostacyclin (PGI2), as suggested from PG RIAs, but an epoxy-eicosatrienoic acid (EET), identified as the 11, 12 isomer by HPLC and MS/MS. The synthesis of this EET is probably cytochrome P-450 monooxygenase dependent. Its potential role in the development of the KS tumor cells is under investigation. C1 INST PASTEUR,INSERM,U207,URIA,F-75724 PARIS 15,FRANCE. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. INST GUSTAVE ROUSSY,CNRS,URA 158,F-94805 VILLEJUIF,FRANCE. NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. NR 29 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD OCT 13 PY 1992 VL 1180 IS 1 BP 83 EP 90 DI 10.1016/0925-4439(92)90030-Q PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JT839 UT WOS:A1992JT83900012 PM 1390946 ER PT J AU GAK, E TAYLOR, WG CHAN, AML RUBIN, JS AF GAK, E TAYLOR, WG CHAN, AML RUBIN, JS TI PROCESSING OF HEPATOCYTE GROWTH-FACTOR TO THE HETERODIMERIC FORM IS REQUIRED FOR BIOLOGICAL-ACTIVITY SO FEBS LETTERS LA English DT Article DE HEPATOCYTE GROWTH FACTOR; SCATTER FACTOR; POSTTRANSLATIONAL MODIFICATION; PLASMINOGEN ID SCATTER FACTOR; EPITHELIAL-CELLS; MOLECULAR-CLONING; HEPATOPOIETIN-A; RAT PLATELETS; PURIFICATION; KERATINOCYTES; IDENTIFICATION; FIBROBLASTS; ACTIVATION AB Hepatocyte growth factor is a plasminogen-like molecule with diverse biological effects. Although it is synthesized as a single chain polypeptide, it was originally purified as a disulfide-linked heterodimer which was generated by an internal proteolytic event. Subsequent work indicated that preparations consisting largely of the monomeric form also exhibited potent activity. By using a combination of protease inhibition and site-directed mutagenesis, we established that conversion of the single chain polypeptide to the heterodimer occurred during the bioassay and was required for mitogenic and motogenic activity. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 37 TC 80 Z9 81 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 OCT 12 PY 1992 VL 311 IS 1 BP 17 EP 21 DI 10.1016/0014-5793(92)81356-Q PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA JU076 UT WOS:A1992JU07600004 PM 1383032 ER PT J AU DEERAUSQUIN, G BROOKER, G HANBAUER, I AF DEERAUSQUIN, G BROOKER, G HANBAUER, I TI K+-EVOKED DOPAMINE RELEASE DEPENDS ON A CYTOSOLIC CA2+ POOL REGULATED BY N-TYPE CA2+ CHANNELS SO NEUROSCIENCE LETTERS LA English DT Article DE PRIMARY CULTURE; MESENCEPHALON; DOPAMINE RELEASE; CA2+ CHANNEL; SPATIAL SIGNAL; FURA-2 FLUORESCENCE; SINGLE-CELL CALCIUM IMAGING ID CALCIUM CHANNELS; MESENCEPHALIC NEURONS; PYRAMIDAL NEURONS; PRIMARY CULTURES; CA-2+ CHANNELS; H-3 DOPAMINE; CELLS; ACTIVATION; DYNAMICS; SITES AB Membrane depolarization evoked by 25-40 mM K+ elicited an immediate increase of somatic and neuritic [Ca2+]i in cultured dopaminergic neurons as measured by digital fluorescence microscope imaging. The rise of neuritic [Ca2+]i was inhibited by N-type but not L-type Ca2+ channel blockers, while the rise of somatic [Ca2+]i was prevented by both L- and N-type Ca2+ channel blockers. Similarly, depolarization-induced [H-3]dopamine release was selectively attenuated by N-type Ca2+ channel blockers. The present results suggest that [H-3]dopamine release from mesencephalic neuronal cell cultures relates to a Ca2+-dependent mechanism regulated by N-type channels located in the vicinity of the exocytotic sites within neuritic processes. C1 NHLBI,CHEM PHARMACOL LAB,BLDG 10,RM 8N-102,BETHESDA,MD 20892. GEORGETOWN UNIV,FIDIA GEORGETOWN INST NEUROSCI,WASHINGTON,DC 20007. RI de Erausquin, Gabriel/G-5840-2010 OI de Erausquin, Gabriel/0000-0001-6423-4461 FU NHLBI NIH HHS [HL28940] NR 15 TC 14 Z9 14 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 12 PY 1992 VL 145 IS 2 BP 121 EP 125 DI 10.1016/0304-3940(92)90001-N PG 5 WC Neurosciences SC Neurosciences & Neurology GA JV688 UT WOS:A1992JV68800001 PM 1334537 ER PT J AU WANG, SZ ZHU, SZ JOSEPH, JA ELFAKAHANY, EE AF WANG, SZ ZHU, SZ JOSEPH, JA ELFAKAHANY, EE TI COMPARISON OF THE LEVEL OF MESSENGER-RNA ENCODING M1 AND M2 MUSCARINIC RECEPTORS IN BRAINS OF YOUNG AND AGED RATS SO NEUROSCIENCE LETTERS LA English DT Article DE MUSCARINIC RECEPTOR; AGING; RECEPTOR SUBTYPE; MESSENGER RNA; RAT BRAIN; SOLUTION HYBRIDIZATION ID PHOSPHOINOSITIDE HYDROLYSIS; STRIATAL DOPAMINE; DYSFUNCTION; INHIBITION; SENESCENCE; SUBTYPES; BINDING AB We compared the concentration of mRNA encoding the m1 and m2 muscarinic receptors in several brain regions obtained from young (5-8 months) and aged (24-28 months) male Fischer 344 rats. DNA-excess solution hybridization was employed as a quantitative measure of mRNA concentration. The results indicate the absence of changes in the ml receptor message with aging in the cerebral cortex, hippocampus and striatum. While there was no statistically significant aging-associated alteration in the concentration of the message encoding the m2 receptor in the thalamus, midbrain, cerebellum and brainstem, there was a decrease in the message level in the hypothalamus. C1 UNIV MINNESOTA,SCH MED,DIV NEUROSCI RES PSYCHIAT,BOX 392,MAYO BLDG,MINNEAPOLIS,MN 55455. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 18 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 12 PY 1992 VL 145 IS 2 BP 149 EP 152 DI 10.1016/0304-3940(92)90008-U PG 4 WC Neurosciences SC Neurosciences & Neurology GA JV688 UT WOS:A1992JV68800008 PM 1465211 ER PT J AU HEYES, MP AF HEYES, MP TI QUINOLINIC ACID IN CULTURE MEDIA USED FOR INVITRO NEUROTOXICOLOGY STUDIES SO NEUROSCIENCE LETTERS LA English DT Article DE QUINOLINIC ACID; NMDA RECEPTOR; NEUROTOXICITY; INVITRO ID METHYL-D-ASPARTATE; RAT-BRAIN; SERUM; DAMAGE; HIV-1 AB Serum from several species is frequently added to the incubation media of cells in vitro. The excitotoxin and N-methyl-D-aspartate receptor agonist quinolinic acid was found to be present in serum in concentrations ranging from 59 to 4895 nM. Some neuronal systems are reported to be particularly sensitive to the neurotoxic effects of quinolinic acid. Therefore, quinolinic acid in serum should be considered as a potentially confounding variable in neurotoxicology studies in vitro. RP HEYES, MP (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,ROOM 3D40,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 12 PY 1992 VL 145 IS 2 BP 234 EP 235 DI 10.1016/0304-3940(92)90030-B PG 2 WC Neurosciences SC Neurosciences & Neurology GA JV688 UT WOS:A1992JV68800030 PM 1465223 ER PT J AU CHOW, TYK PERKINS, EL RESNICK, MA AF CHOW, TYK PERKINS, EL RESNICK, MA TI YEAST RNC1 ENCODES A CHIMERIC PROTEIN, RHONUC, WITH A HUMAN RHO MOTIF AND DEOXYRIBONUCLEASE ACTIVITY SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NEUROSPORA ENDO-EXONUCLEASE; FUNCTIONAL RAD52 GENE; DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; DNA-REPAIR; MITOTIC RECOMBINATION; MOLECULAR MECHANISM; CONSERVED STRUCTURE; GTPASE SUPERFAMILY AB The yeast Saccharomyces cerevisiae contains an endo-exonuclease yNucR that has been implicated in both recombination and repair. We describe the isolation and characterization of the corresponding gene. Within the predicted N-terminal half of the protein there is extensive homology (approximately 50%) with human rho genes, which are related to the ras oncogene, particularly in the proposed GTP-binding region. The C-terminal region, which is related to the Escherichia coli recC protein, presumably encodes the endo-exonuclease activity. The yNucR may thus represent a new class of GTP-binding proteins. Because of the chimeric nature of the polypeptide, this protein is renamed RhoNUC (rather than the original yNucR) and the gene is RNC1 for Rho-associated-NuClease. Over expression of the gene leads to altered cell growth and nuclear morphology. We propose that the gene plays an important role in cell development as well as DNA repair/recombination. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. RP CHOW, TYK (reprint author), UNIV SHERBROOKE,FAC MED,DEPT NUCL MED & RADIOBIOL,SHERBROOKE J1H 5N4,QUEBEC,CANADA. NR 42 TC 15 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 11 PY 1992 VL 20 IS 19 BP 5215 EP 5221 DI 10.1093/nar/20.19.5215 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV092 UT WOS:A1992JV09200038 PM 1408836 ER PT J AU DESIMONE, R AF DESIMONE, R TI THE PHYSIOLOGY OF MEMORY - RECORDINGS OF THINGS PAST SO SCIENCE LA English DT Editorial Material ID INFERIOR TEMPORAL CORTEX; SHORT-TERM-MEMORY; HIPPOCAMPAL-FORMATION; RECOGNITION MEMORY; NEURONS; LESIONS; ASSOCIATION; RESPONSES; MACAQUE; PRIMATE RP DESIMONE, R (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 32 TC 55 Z9 55 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 OCT 9 PY 1992 VL 258 IS 5080 BP 245 EP 246 DI 10.1126/science.1411523 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JR860 UT WOS:A1992JR86000021 PM 1411523 ER PT J AU HENDEY, B KLEE, CB MAXFIELD, FR AF HENDEY, B KLEE, CB MAXFIELD, FR TI INHIBITION OF NEUTROPHIL CHEMOKINESIS ON VITRONECTIN BY INHIBITORS OF CALCINEURIN SO SCIENCE LA English DT Article ID FREE CALCIUM; POLYMORPHONUCLEAR LEUKOCYTES; CELLULAR-REGULATION; CYCLOSPORINE-A; PROTEIN; DOMAIN; FIBRONECTIN; RECEPTORS; CELLS; IDENTIFICATION AB Migration of human polymorphonuclear neutrophils on vitronectin is dependent on repeated transient increases in the concentration of intracellular free calcium ([Ca2+]i). A specific peptide inhibitor of the Ca2+-calmodulin-dependent phosphatase calcineurin was introduced into the cytoplasm of neutrophils. The peptide inhibited neutrophil migration on vitronectin by interfering with the release of the cells from sites of attachment. A similar reduction in motility on vitronectin occurred when cells were treated with the immunosuppressant FK506, which also inhibits calcineurin when bound to its binding protein, FKBP. These results indicate that a rise in [Ca2+]i reduces integrin-mediated adhesion to vitronectin by a mechanism that requires calcineurin activity. C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT PHYSIOL,NEW YORK,NY 10032. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI Maxfield, Fred/A-1718-2011; OI Maxfield, Frederick/0000-0003-4396-8866 FU NIGMS NIH HHS [GM14150, GM34770] NR 29 TC 173 Z9 173 U1 1 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 9 PY 1992 VL 258 IS 5080 BP 296 EP 299 DI 10.1126/science.1384129 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JR860 UT WOS:A1992JR86000033 PM 1384129 ER PT J AU OLSON, CR MUSIL, SY AF OLSON, CR MUSIL, SY TI TOPOGRAPHIC ORGANIZATION OF CORTICAL AND SUBCORTICAL PROJECTIONS TO POSTERIOR CINGULATE CORTEX IN THE CAT - EVIDENCE FOR SOMATIC, OCULAR, AND COMPLEX SUBREGIONS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE CINGULATE; RETROSPLENIAL; CONNECTIONS; CAT ID AUDITORY ASSOCIATION AREAS; CEREBRAL-CORTEX; RHESUS-MONKEY; THALAMIC AFFERENTS; EYE-MOVEMENTS; LIMBIC CORTEX; FRONTAL-LOBE; PHYSIOLOGICAL-PROPERTIES; FUNCTIONAL-ORGANIZATION; AMYGDALOID COMPLEX AB The posterior cingulate area (CGp) of the cat consists of cortex on the exposed cingulate gyrus and in the adjacent ventral bank of the splenial sulcus. We have placed deposits of distinguishable fluorescent tracers at multiple restricted sites in CGp and have analyzed the distribution throughout the forebrain of neurons labeled by retrograde transport. Cortical projections to CGp arise (in approximately descending order of strength) from anterior cingulate cortex; prefrontal cortex and premotor areas including the frontal eye fields; visual areas including especially areas 7 and 20b; parahippocampal areas; insular cortex; somesthetic areas; and auditory areas. Corticocortical pathways are organized topographically with respect to the posterior-anterior axis in CGp. Projections from prefrontal cortex and other areas with complex (as opposed to sensory, motor, or limbic) functions are concentrated posteriorly; projections from visual and oculomotor areas are concentrated at an intermediate level; and projections from areas with somesthetic and somatomotor functions are concentrated anteriorly. Thalamic projections to CGp arise from the anterior nuclei (AD, AV, and AM), from restricted portions of the ventral complex (VAd, VAm, and VMP), from discrete sectors of the lateral complex (LD, LPs, and LPm), from the rostral crescent of intralaminar nuclei (CM, PC, and CL), and from the reuniens nucleus. Projections from AM, VAd, LD, and LPs are spatially ordered in the sense that more ventral thalamic neurons project to more anterior cortical sites. Projections from AV and AD are stronger at more posterior cortical sites but do not show other signs of topographic ordering. Projections from LPm, CM, PC, CL, and RE are diffuse. We conclude (1) that cortical afferents of CGp derive predominantly from neocortical areas including those with well established sensory and motor functions; (2) that limbic projections to CGp originate primarily in structures, including the hippocampus, which are associated with memory, as opposed to structures, including the amygdala, which are associated with emotional and instinctual behavior; and (3) that CGp contains subregions in which complex, ocular, or somatic afferents predominate. C1 NEI,SENSOR MOTOR RES LAB,BETHESDA,MD 20892. RP OLSON, CR (reprint author), UNIV MARYLAND,COLL DENT SURG,DEPT ANAT,BALTIMORE,MD 21201, USA. FU NINDS NIH HHS [1 RO1 NS27287] NR 86 TC 46 Z9 46 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 OCT 8 PY 1992 VL 324 IS 2 BP 237 EP 260 DI 10.1002/cne.903240207 PG 24 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA JP420 UT WOS:A1992JP42000006 PM 1430331 ER PT J AU RESNICK, JL BIXLER, LS CHENG, LZ DONOVAN, PJ AF RESNICK, JL BIXLER, LS CHENG, LZ DONOVAN, PJ TI LONG-TERM PROLIFERATION OF MOUSE PRIMORDIAL GERM-CELLS IN CULTURE SO NATURE LA English DT Article ID DIFFERENTIATION INHIBITING ACTIVITY; EMBRYOS; GROWTH AB PRIMORDIAL germ cells(PGCs) are first identifiable as a population of about eight alkaline phosphatase-positive cells in the 7.0 days postcoitum mouse embryo1. During the next 6 days of development they proliferate to give rise to the 25,000 cells that will establish the meiotic population2. Steel factor is required for PGC survival both in vivo3 and in vitro4,5 and together with leukaemia inhibitory factor stimulates PGC proliferation in vitro6. In feeder-dependent culture, PGCs will proliferate for up to 7 days, but their numbers eventually decline and their proliferative capacity is only a fraction of that seen in vivo6,7. Here we report a further factor that stimulates PGC proliferation in vitro, basic fibroblast growth factor (bFGF). Furthermore, bFGF, in the presence of steel factor and leukaemia inhibitory factor, stimulates long-term proliferation of PGCs, leading to the derivation of large colonies of cells. These embryonic germ cells resemble embryonic stem cells, pluripotent cells derived from preimplantation embryos, or feeder-dependent embryonal carcinoma cells, pluripotent stem cells of PGC-derived tumours (teratomas and teratocarcinomas)8. To our knowledge, these results provide the first system for long-term culture of PGCs. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. RP RESNICK, JL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,POB B,FREDERICK,MD 21702, USA. NR 16 TC 610 Z9 659 U1 2 U2 13 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 8 PY 1992 VL 359 IS 6395 BP 550 EP 551 DI 10.1038/359550a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JR859 UT WOS:A1992JR85900064 PM 1383830 ER PT J AU CLARKE, R CURRIER, S KAPLAN, O LOVELACE, E BOULAY, V GOTTESMAN, MM DICKSON, RB AF CLARKE, R CURRIER, S KAPLAN, O LOVELACE, E BOULAY, V GOTTESMAN, MM DICKSON, RB TI EFFECT OF P-GLYCOPROTEIN EXPRESSION ON SENSITIVITY TO HORMONES IN MCF-7 HUMAN BREAST-CANCER CELLS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GROWTH-FACTOR RECEPTOR; MULTIDRUG RESISTANCE; MONOCLONAL-ANTIBODIES; MALIGNANT PROGRESSION; ACQUIRED-RESISTANCE; TAMOXIFEN; DOXORUBICIN; INVITRO; DRUGS; ESTRADIOL AB Background: Data obtained from studies of primary human breast cancers and established cell lines indicate that overexpression of the MDR1 gene (also known as PGY1) is associated with decreased expression of steroid hormone receptors and increased expression of epidermal growth factor (EGF) receptors. Other study results indicate that both progestins and triphenylethylene antiestrogens may be substrates for P-glycoprotein, the product of the MDR1 gene. These findings together suggest an association between overexpression of the MDR1 gene and cross-resistance to progestin and antiestrogen therapies. Purpose: This study was designed to determine (a) the ability of MDR1 expression to alter tumor sensitivity to hormone therapy and (b) the role of MDR1 expression in expression of functional hormone receptors in human breast cancer. Methods: We transduced MCF-7 cells with MDR1 complementary DNA, using a retroviral vector directing the constitutive expression of the MDR1 gene. Transduced cells (MCF-7MDR1) were examined for ability to produce P-glycoprotein, expression of steroid hormone receptors, and responsivity to antiestrogens. For comparison, we used MCF-7ADR human breast cancer cells, which overexpress MDR1 and have also lost the requirement for 17beta-estradiol supplementation to form tumors in nude mice. We also investigated the level of EGF-R mRNA expression by using a sensitive RNase protection analysis. Results: MCF-7MDR1 cells retained both estrogen receptor and progesterone receptor expression as well as sensitivity to 4-hydroxytamoxifen. Expression of the estrogen-inducible pS2 and EGF receptor genes was similar in parental MCF-7 and transduced MCF-7MDR1 cells. EGF receptor expression was increased, and pS2 expression was lost (undetectable) in MCF-7ADR cells. Conclusions: The data indicate that overexpression of the MDR1 gene alone confers a multidrug-resistant phenotype, but it does not directly result in either cross-resistance to antiestrogens or a loss of steroid hormone receptor expression. Implications: MCF-7MDR1 cells provide an important model for study of the interactions of cytotoxic drugs, hormones, and the MDR1 glycoprotein in human hormone-responsive breast cancer cells. C1 NCI,DIV CANC BIOL DIAG & CTR,CELL BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. RP CLARKE, R (reprint author), GEORGETOWN UNIV,SCH MED,VINCENT T LOMBARDI CANC RES CTR,RM S128A,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 FU NCI NIH HHS [UO1CA-51908] NR 36 TC 51 Z9 51 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 OCT 7 PY 1992 VL 84 IS 19 BP 1506 EP 1512 DI 10.1093/jnci/84.19.1506 PG 7 WC Oncology SC Oncology GA JQ627 UT WOS:A1992JQ62700018 PM 1359153 ER PT J AU DABHOLKAR, M BOSTICKBRUTON, F WEBER, C BOHR, VA EGWUAGU, C REED, E AF DABHOLKAR, M BOSTICKBRUTON, F WEBER, C BOHR, VA EGWUAGU, C REED, E TI ERCC1 AND ERCC2 EXPRESSION IN MALIGNANT-TISSUES FROM OVARIAN-CANCER PATIENTS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID EXCISION REPAIR GENE; HOST-CELL REACTIVATION; DNA-REPAIR; MOLECULAR-CLONING; BIOLOGICAL CHARACTERIZATION; CISPLATIN RESISTANCE; DAMAGED PLASMID; CDNA CLONING; LINE; CIS-DIAMMINEDICHLOROPLATINUM(II) AB Background: ERCC1 and ERCC2 are human DNA repair genes that are associated with in vitro resistance to selected DNA-damaging agents. Purpose: Fresh tumor tissues from 26 patients with ovarian cancer were analyzed for the RNA levels of expression of these genes to determine possible clinical relevance. Methods: Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol. Clinical response was assessed by standard criteria. Gene expression level was assessed by slot blot analysis, using beta-actin as a control. Relative expression levels were determined by comparing each tumor sample with a Chinese hamster ovary cell line that had a stable transfection of the human ERCC1 gene. Results: Patients who were clinically resistant to platinum-based therapy had a 2.6-fold higher expression level of ERCC1 in their tumor tissue than did patients who responded to that therapy (P = .015). Results obtained by slot blot analysis were qualitatively confirmed by polymerase chain reaction analysis. Relative levels of expression of ERCC2 did not differ significantly between responders and nonresponders. Conclusion: We conclude that ERCC1 expression levels in hu. man tumor tissue may have a role in clinical resistance to platinum compounds. These data appear to be consistent with the assertion that ERCC1 serves as an excision nuclease, whereas ERCC2 serves as a helicase. C1 NCI,DIV CANC TREATMENT,MED BRANCH,CLIN ONCOL PROGRAM,BLDG 10,RM 12N226,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. LAWRENCE LIVERMORE NATL LAB,DIV BIOMED SCI,LIVERMORE,CA 94550. NEI,IMMUNOL LAB,BETHESDA,MD 20892. NR 26 TC 250 Z9 258 U1 0 U2 4 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 OCT 7 PY 1992 VL 84 IS 19 BP 1512 EP 1517 DI 10.1093/jnci/84.19.1512 PG 6 WC Oncology SC Oncology GA JQ627 UT WOS:A1992JQ62700019 PM 1433335 ER PT J AU DONG, A CAUGHEY, B CAUGHEY, WS BHAT, KS COE, JE AF DONG, A CAUGHEY, B CAUGHEY, WS BHAT, KS COE, JE TI SECONDARY STRUCTURE OF THE PENTRAXIN FEMALE PROTEIN IN WATER DETERMINED BY INFRARED-SPECTROSCOPY - EFFECTS OF CALCIUM AND PHOSPHORYLCHOLINE SO BIOCHEMISTRY LA English DT Article ID C-REACTIVE PROTEIN; AMYLOID-P-COMPONENT; AMINO-ACID-SEQUENCE; QUANTITATIVE IR SPECTROPHOTOMETRY; GALACTOSE-BINDING PROTEIN; RESIDUE ABSORPTION-BANDS; CIRCULAR-DICHROISM; SYRIAN-HAMSTER; SPECTRAL PARAMETERS; PEPTIDE COMPOUNDS AB The secondary structure of hamster female protein in aqueous solutions in the presence or absence of calcium and phosphorylcholine has been investigated using Fourier transform infrared spectroscopy. Our present studies provide the first evaluation of the secondary structure of FP and its calcium- and phosphorylcholine-dependent conformational changes. Quantitative analysis indicated that FP is composed of 50% betA-sheet, 11% alpha-helix, 29% beta-turn, and 10% random structures. Calcium- and phosphorylcholine-dependent infrared spectral changes were observed in regions assigned to beta-sheet, alpha-helix, turn, and random structures. The infrared-based secondary structure compositions were used as constraints to compute theoretical locations for the different secondary structures along the amino acid sequence of the FP protein. Two putative calcium-binding sites were proposed for FP (residues 93-109 and 150-168) as well as other members of the pentraxin family on the basis of the theoretical secondary structure predictions and the similarity in sequence between the pentraxins and EF-hand calcium-binding proteins. The changes in protein conformation detected upon binding of calcium and phosphorylcholine provide a mechanism for the effects of these ligands on physiologically important properties of the protein, e.g., activation of complement and association with amyloids. C1 COLORADO STATE UNIV,DEPT BIOCHEM,FT COLLINS,CO 80523. NIAID,ROCKY MT LABS,HAMILTON,MT 59840. NR 62 TC 54 Z9 55 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 6 PY 1992 VL 31 IS 39 BP 9364 EP 9370 DI 10.1021/bi00154a006 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR320 UT WOS:A1992JR32000006 PM 1382589 ER PT J AU KRUMBIEGEL, M DIMITROV, DS PURI, A BLUMENTHAL, R AF KRUMBIEGEL, M DIMITROV, DS PURI, A BLUMENTHAL, R TI DEXTRAN SULFATE INHIBITS FUSION OF INFLUENZA-VIRUS AND CELLS EXPRESSING INFLUENZA HEMAGGLUTININ WITH RED-BLOOD-CELLS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE DEXTRAN SULFATE; INFLUENZA VIRUS; GP4F CELL; FUSION ID HUMAN IMMUNODEFICIENCY VIRUS; VESICULAR STOMATITIS-VIRUS; PH-DEPENDENT FUSION; MEMBRANE-FUSION; CONFORMATIONAL CHANGE; FLUORESCENCE; REPLICATION; EVENTS; FIBROBLASTS; ACTIVATION AB The influence of dextran sulfate with molecular weights of 500 000 and 8000 on binding and fusion of influenza virus (X31 strain) and of cells expressing influenza hemagglutinin (GP4F) with red blood cells (RBC) was investigated by spectrofluorimetry using virus and RBC labeled with the fluorescent dye octadecyl rhodamine B (R18). There was no significant inhibition of binding of virus and GP4F cells to red blood cells by dextran sulfate, but the polymer strongly inhibited the low pH induced fusion. Virus-RBC fusion was completely blocked by the high molecular weight dextran sulfate at concentrations as low as 0.5 mg/ml. Inhibition of RBC-GP4F cell fusion by dextran sulfate in the same concentration range was not as pronounced but the effect was potentiated by Ca2+. The polymer was only inhibitory when added at early steps of the fusion reaction, but the pH-induced conformational change of the hemagglutinin was not affected by dextran sulfate as measured by its susceptibility to proteolytic digestion. Removal of dextran sulfate after low pH-requiring steps allowed the system to fuse at neutral pH indicating that the inhibitory effect requires the continuous presence of dextran sulfate during the fusion reaction. C1 KARL MARX UNIV LEIPZIG,INST BIOPHYS,O-7010 LEIPZIG,GERMANY. NCI,LMMB,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 26 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD OCT 5 PY 1992 VL 1110 IS 2 BP 158 EP 164 DI 10.1016/0005-2736(92)90353-N PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JT015 UT WOS:A1992JT01500005 PM 1390844 ER PT J AU HOLMES, SE SINGER, MF SWERGOLD, GD AF HOLMES, SE SINGER, MF SWERGOLD, GD TI STUDIES ON P40, THE LEUCINE ZIPPER MOTIF-CONTAINING PROTEIN ENCODED BY THE 1ST OPEN READING FRAME OF AN ACTIVE HUMAN LINE-1 TRANSPOSABLE ELEMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COILED-COIL; SEQUENCE; FAMILY; CELLS; END; DNA AB Full-length human LINE-1 retrotransposons encode p40 proteins with varying electrophoretic mobilities under denaturing conditions. The p40 expressed from the first open reading frame in the LINE-1 copy designated L1.2A co-electrophoreses with the endogenous p40 in human teratocarcinoma cells. This finding is consistent with previous data indicating that L1.2A is an active element. The amino acid sequence in the central region of the L1.2A p40 accounts, at least in part, for its characteristic mobility. This region includes sequences which can, in principle, form a leucine zipper. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,DEPT PEDIAT & MED,BALTIMORE,MD 21205. CARNEGIE INST WASHINGTON,WASHINGTON,DC 20005. NR 27 TC 75 Z9 75 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 OCT 5 PY 1992 VL 267 IS 28 BP 19765 EP 19768 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800004 PM 1328181 ER PT J AU OREILLY, MA GEISER, AG KIM, SJ BRUGGEMAN, LA LUU, AX ROBERTS, AB SPORN, MB AF OREILLY, MA GEISER, AG KIM, SJ BRUGGEMAN, LA LUU, AX ROBERTS, AB SPORN, MB TI IDENTIFICATION OF AN ACTIVATING TRANSCRIPTION FACTOR (ATF) BINDING-SITE IN THE HUMAN TRANSFORMING GROWTH-FACTOR-BETA-2 PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL SUPPRESSOR FACTOR; FACTOR-BETA; SEQUENCE-ANALYSIS; GENE-EXPRESSION; FUNCTIONAL-CHARACTERIZATION; AP-1 COMPLEX; CDNA CLONES; TGF BETA-1; PROTEIN; EMBRYOGENESIS AB Transforming growth factor TGF-beta2 is encoded by multiple mRNA transcripts of 5.8, 5.1, 4.0, 3.8, and 2.8 kilobase pairs (kb) that are expressed in various human and monkey cells. Northern blot analysis using genomic fragments of DNA was used to demonstrate that some of this size heterogeneity is due to differences in the length of the 5'-untranslated region. Probes that were colinear with the first 600 nucleotides of the 5'-untranslated region detected only the 5.8-, 4.0-, and 3.8-kb transcripts. In order to identify DNA elements that regulate the transcription of these mRNA transcripts, deletion constructs of 5'-flanking DNA were ligated to the coding region for chloramphenicol acetyltransferase (CAT) and analyzed for promoter activity in several cell lines. Sequences responsible for putative enhancer and silencer regions were identified between -778 and -40 relative to the transcription initiation site. Addition of a cyclic AMP-responsive element/activating transcription factor-like element at -74 resulted in a 5-10-fold increase in CAT activity over that expressed with a construct that contained only the TATA box. This increase in CAT activity was suppressed by the addition of DNA sequences between -257 and -187, whereas sequences between -778 and -257 stimulated CAT activity. Point mutations within the ATF binding site at -74 resulted in a marked decrease in CAT expression. Cotransfection with ATF-1 or ATF-2 expression plasmids resulted in both dose-dependent stimulatory and inhibitory activities that were cell type-dependent. These studies identify multiple transcription initiation sites for TGF-beta2 and demonstrate that transcription from one of these promoters is dependent upon an ATF binding site located 5' of the TATA box. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP OREILLY, MA (reprint author), NCI,CHEMOPREVENT LAB,BLDG 41,RM C629,BETHESDA,MD 20892, USA. NR 40 TC 57 Z9 58 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 1992 VL 267 IS 28 BP 19938 EP 19943 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800033 PM 1400310 ER PT J AU BUSAM, KJ ROBERTS, AB SPORN, MB AF BUSAM, KJ ROBERTS, AB SPORN, MB TI INHIBITION OF MITOGEN-INDUCED C-FOS EXPRESSION IN MELANOMA-CELLS BY RETINOIC ACID INVOLVES THE SERUM RESPONSE ELEMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR; INDUCIBLE BINDING; GENE-EXPRESSION; ANTISENSE RNA; VITAMIN-A; TRANSCRIPTION; INDUCTION; ACTIVATION; SEQUENCES; ONCOGENE AB To investigate the mechanism(s) by which all-trans-retinoic acid (RA) inhibits cell growth, we studied its effect on the expression of c-fos and c-jun in B16 melanoma cells. RA differentially inhibited proto-oncogene induction by mitogens, such as phorbol 12-myristate 13-acetate and serum. Suppression of c-fos was achieved with doses of RA as low as 10(-10) M and required pretreatment of cells with RA for a minimum of 2 h. In contrast, inhibition of c-jun required pretreatment for greater than 16 h with at least 10(-8) M RA and coincided with the observed decrease in cell growth. RA blocked c-fos induction by inhibiting transcription. This inhibition of transcription occurs through the serum response element (SRE), since the SRE alone was sufficient to confer down-regulation by RA to a minimal c-fos promoter construct. Thus, the SRE plays a critical role in the suppression of c-fos transcription by RA. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 55 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 1992 VL 267 IS 28 BP 19971 EP 19977 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800038 PM 1400313 ER PT J AU PENNYPACKER, KR HONG, JS DOUGLASS, J MCMILLIAN, MK AF PENNYPACKER, KR HONG, JS DOUGLASS, J MCMILLIAN, MK TI CONSTITUTIVE EXPRESSION OF AP-1 TRANSCRIPTION FACTORS IN THE RAT ADRENAL - EFFECTS OF NICOTINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; NERVE GROWTH-FACTOR; C-FOS EXPRESSION; MESSENGER-RNA; PHOSPHORYLATION; JUN; ACTIVATION; PROTEINS; PROENKEPHALIN; MEDULLA AB The AP-1 proteins (c-fos and fos-related antigens and jun proteins) are transcription factors that are induced in most cells by various stimuli, but the expression of these proteins is low or undetectable in the basal state. Our data indicate that the rat adrenal gland contains a basally expressed elevated level of AP-1 proteins and mRNAs (40- and 35-kDa fos-related antigens, a 39-kDa c-jun protein, c-jun, junB, and junD mRNA), as well as high basal AP-1 DNA binding activity. Both the medulla and cortex contained equivalent levels of fos-related antigens and c-jun protein; however, the majority of AP-1 DNA binding was detected in the medulla. Handling of rats for several days prior to sacrifice failed to affect protein expression or binding; on the other hand, repeated injections of nicotine increased AP-1 DNA binding. A single nicotine injection 60 min prior to removing the adrenals caused a significant reduction in AP-1 DNA binding without any detectable changes in AP-1 protein expression. Pretreatment of adrenal nuclear extracts with alkaline phosphatase prior to incubation with the AP-1 oligomer decreased binding activity. Thus, unlike most tissues where AP-1 DNA binding activity is controlled by increased expression of AP-1 proteins, DNA binding in the rat adrenal gland appears to be controlled at the post-translational level, possibly through dephosphorylation. C1 OREGON HLTH SCI UNIV,INST VOLLUM,PORTLAND,OR 97201. RP PENNYPACKER, KR (reprint author), NIEHS,NEUROPHARMACOL SECT,MOLEC & INTEGRAT NEUROSCI LAB,MD 14-06,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 39 TC 39 Z9 39 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 1992 VL 267 IS 28 BP 20148 EP 20152 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800064 PM 1400333 ER PT J AU TERCERO, JC RILES, LE WICKNER, RB AF TERCERO, JC RILES, LE WICKNER, RB TI LOCALIZED MUTAGENESIS AND EVIDENCE FOR POSTTRANSCRIPTIONAL REGULATION OF MAK3 - A PUTATIVE N-ACETYLTRANSFERASE REQUIRED FOR DOUBLE-STRANDED-RNA VIRUS PROPAGATION IN SACCHAROMYCES-CEREVISIAE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-ACETYLTRANSFERASE; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; CHORISMATE MUTASE; LACZ FUSIONS; CELL-GROWTH; YEAST; GENE; PROTEIN; DNA AB The MAK3 gene of Saccharomyces cerevisiae is necessary for the propagation of the L-A double-stranded RNA virus and its satellites, such as M1 that encodes a killer toxin. We cloned the MAK3 gene based on its genetic map position using physically mapped lambda-clones covering nearly all of the yeast genome. The minimal sequence necessary to complement the mak3-1 mutation contained 3 open reading frames (ORFs). Only one (ORF3) was necessary to complement mak3-1. A deletion insertion mutant of ORF3 grew slowly on nonfermentable carbon sources, an effect not due simply to its loss of L-A. Although ORF3 alone is sufficient for MAK3 activity when expressed from an expression vector, in its native context an additional 669 base pairs 3' to the ORF and complementary to the gene for a non-histone protein are necessary for expression, but not for normal steady state transcript levels. This suggests a posttranscriptional control of MAK3 expression by the 3' region. The MAK3 protein has substantial homology with several N-acetyltransferases with consensus patterns h..h.h...Y..[HK]GI[AG][KR].Lh...h and h.h[DE] ....N..A...Y...GF.........Y...[DE]G, (h = hydrophobic). Mutation of any of the underlined conserved residues (94GI --> AA, 123N --> A, 130Y --> A, 134GF --> SL, 144Y --> A, and 149G --> A) inactivated the gene, supporting the hypothesis that MAK3 encodes an N-acetyltransferase. C1 WASHINGTON UNIV, SCH MED, DEPT GENET, ST LOUIS, MO 63110 USA. RP NIDDKD, GENET SIMPLE EUKARYOTES SECT, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 54 TC 66 Z9 68 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 OCT 5 PY 1992 VL 267 IS 28 BP 20270 EP 20276 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800082 PM 1339437 ER PT J AU TERCERO, JC WICKNER, RB AF TERCERO, JC WICKNER, RB TI MAK3 ENCODES AN N-ACETYLTRANSFERASE WHOSE MODIFICATION OF THE L-A GAG NH2 TERMINUS IS NECESSARY FOR VIRUS PARTICLE ASSEMBLY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRANDED-RNA; CAPSID PROTEIN VP4; SACCHAROMYCES-CEREVISIAE; COAT PROTEIN; YEAST; GENES; MYRISTYLATION; INVIVO; IDENTIFICATION; REPLICATION AB The MAK3 gene is necessary for propagation of the L-A double-stranded RNA virus of Saccharomyces cerevisiae. MAK3 encodes a protein with substantial homology to the Escherichia coli rimI N-acetyltransferase that acetylates the NH, terminus of ribosomal protein S18, and shares consensus sequences with a group of N-acetyltransferases. The NH2 terminus of the viral major coat protein encoded by L-A is normally blocked, but we find that it is unblocked in a mak3-1 mutant. L-A virus-encoded proteins produced from a cDNA clone of L-A can encapsidate the L-A (+)-strands in a wild-type host, but not in a mak3-1 mutant strain. The amount of major coat protein found in the particle fraction is reduced >100-fold, and the amount in the total cell extract is reduced 5-10-fold. A modified beta-galactosidase, having as its NH2-terminal the NH2-terminal 13 residues of the L-A-encoded major coat protein, is blocked in a wild-type host, but not in a mak3-1 host. We propose that MAK3 encodes an N-acetyltransferase whose modification of the L-A major coat protein NH2 terminus is essential for viral assembly, and that unassembled coat protein is unstable. RP TERCERO, JC (reprint author), NIDDKD,GENET SIMPLE EUKARYOTES SECT,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 41 TC 79 Z9 82 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 1992 VL 267 IS 28 BP 20277 EP 20281 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800083 PM 1400344 ER PT J AU MAO, XH GREEN, JM SAFER, B LINDSTEN, T FREDERICKSON, RM MIYAMOTO, S SONENBERG, N THOMPSON, CB AF MAO, XH GREEN, JM SAFER, B LINDSTEN, T FREDERICKSON, RM MIYAMOTO, S SONENBERG, N THOMPSON, CB TI REGULATION OF TRANSLATION INITIATION-FACTOR GENE-EXPRESSION DURING HUMAN T-CELL ACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-SYNTHESIS INITIATION; CAP-BINDING-PROTEIN; MESSENGER-RNA; HELA-CELLS; STIMULATES PHOSPHORYLATION; FACTORS EIF-4F; LYMPHOCYTES-T; GROWTH-FACTOR; CLONING; INHIBITION AB Activation of quiescent T cells leads to a dramatic increase in the rate of protein synthesis. It is believed that this pronounced increase of protein synthesis is regulated primarily at the level of translational initiation. Although considerable evidence demonstrates that translational initiation can be regulated at the post-translational level by the phosphorylation/dephosphorylation of translation initiation factors (eIFs) such as eIF-4E and eIF-2alpha, additional mechanisms of eIF gene expression may also play a role in the regulation of translation in quiescent cells and/or during their subsequent induction to enter the cell cycle. To address this issue, gene expression of eIF-2alpha, -4E, and -4A was studied in quiescent human peripheral blood T cells following stimulation through the T cell receptor-CD3 complex. Quiescent T cells expressed low levels of eIF-2alpha, -4E, and -4A mRNAs and proteins as compared to proliferating T cells. Activation of resting T cells resulted in a rapid increase (20-50-fold) in the levels of these three mRNAs. This increase did not require new protein synthesis. Furthermore, transcription rates of these three eIF genes showed only minor increase over the induction period as measured by nuclear run-on assays. Despite the rapid increase in initiation factor mRNA levels, increases in eIF protein levels lagged significantly behind. Western blot analysis also showed that the protein levels of the three eIFs were differentially increased. eIF-4A protein levels increased in proportion to the observed increase in cellular protein synthetic activity while the increases in eIF-4E and eIF-2alpha proteins were proportionately less. The low levels of eIF proteins in quiescent T cells appear to correlate with low protein synthesis rate in such cells. The induction of eIF proteins by post-transcriptional/translational mechanisms appears to contribute to the pronounced stimulation of protein synthesis that occurs during T cell activation. C1 UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,MED CTR,DEPT PATHOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,MED CTR,HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. NHLBI,MOLEC HEMATOL LAB,PROT BIOSYNTH SECT,BETHESDA,MD 20892. MCGILL UNIV,DEPT BIOCHEM,MONTREAL H3G 1Y6,QUEBEC,CANADA. RP MAO, XH (reprint author), UNIV MICHIGAN,MED CTR,DEPT MICROBIOL IMMUNOL,ANN ARBOR,MI 48109, USA. FU NCI NIH HHS [CA54521] NR 56 TC 54 Z9 55 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 OCT 5 PY 1992 VL 267 IS 28 BP 20444 EP 20450 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800108 PM 1400363 ER PT J AU BARTLETT, JD LUETHY, JD CARLSON, SG SOLLOTT, SJ HOLBROOK, NJ AF BARTLETT, JD LUETHY, JD CARLSON, SG SOLLOTT, SJ HOLBROOK, NJ TI CALCIUM IONOPHORE-A23187 INDUCES EXPRESSION OF THE GROWTH ARREST AND DNA DAMAGE INDUCIBLE CCAAT ENHANCER-BINDING PROTEIN (C/EBP)-RELATED GENE, GADD153 - CA2+ INCREASES TRANSCRIPTIONAL ACTIVITY AND MESSENGER-RNA STABILITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-FOS; KINASE-C; INTRACELLULAR CALCIUM; HYDROGEN-PEROXIDE; MAMMALIAN-CELLS; LIVER NUCLEI; HEAT-SHOCK; ACTIVATION; TOXICITY; INHIBITOR AB gadd153 is a CCAAT/enhancer-binding protein (C/EBP)-related gene whose expression is induced in response to growth arrest and DNA damage. This investigation explored the possibility that Ca2+ might play a role in regulating expression of gadd153. We have demonstrated that treatment of HeLa cells with the calcium ionophores A23187 and ionomycin leads to the induction of gadd153 mRNA. The induction was rapid; increases in mRNA were detected by 90 min of treatment, and near maximum levels were achieved within 5-h exposure to A23187. Elevated mRNA levels resulted from both an increase in the rate of gadd153 transcription and an increase in the stability of the gadd153 mRNA. The response was not dependent on protein kinase C nor was it coupled to c-fos expression. Buffering intracellular and extracellular Ca2+ by combined treatment with BAPTA-AM (acetoxymethyl ester form of bis(aminophenoxy)ethane N,N'-tetraacetic acid) and EGTA prevented the induction of gadd153 mRNA by A23187. In addition, these treatments prevented the induction of gadd153 mRNA in response to the DNA damaging agent methyl methanesulfonate. We conclude that intracellular Ca2+ plays a role in regulating gadd153 expression. More specifically, Ca2+ likely plays a role in the induction of gadd153 mRNA following DNA damage. C1 NIA, MOLEC GENET LAB, BALTIMORE, MD 21224 USA. NIA, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. NR 39 TC 121 Z9 121 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 1992 VL 267 IS 28 BP 20465 EP 20470 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR858 UT WOS:A1992JR85800111 PM 1400365 ER PT J AU ZHU, J JHAMANDAS, K YANG, HYT AF ZHU, J JHAMANDAS, K YANG, HYT TI RELEASE OF NEUROPEPTIDE FF (FLFQPQRF-NH2) FROM RAT SPINAL-CORD SO BRAIN RESEARCH LA English DT Article DE FLFQPQRF-NH2; NEUROPEPTIDE FF; FMRF-NH2-LIKE PEPTIDE; SPINAL CORD; SECRETION; ANTIOPIATE ID MORPHINE-MODULATING PEPTIDE; SUBSTANCE-P METABOLITES; DORSAL HORN; BRAIN; FLFQPQRFAMIDE; NOCICEPTION; FMRFAMIDE; IMMUNOREACTIVITY; ABSTINENCE; BINDING AB Neuropeptide FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide FF (NPFF) is highly localized in the dorsal spinal cords where there are also specific NPFF binding sites. Furthermore, there have been studies indicating that NPFF may participate in the regulation of pain threshold in the spinal cord. However, whether NPFF can be released from the spinal cord is not known. The present experiments, using an in vitro superfusion of an isolated whole rat spinal cord, demonstrated that high concentrations of KCl or substance P caused a release of NPFF immunoreactive material (IR) from the spinal cord into the perfusion medium in a calcium-dependent manner. Substance P (1-11) also produced a detectable release of NPFF-IR in vivo although the response was quite variable. The released NPFF-IR was analyzed by an HPLC study and found to consist of NPFF and other minor immunoreactive peptides. Further studies with substance P-related peptides showed that the in vitro release of NPFF-IR could also be induced by substance P (1-7) but not by [pGlu5,Me-Phe8,Sar9]-substance P (5-11) or substance K. These results suggest that the specific substance P receptor (SP-N), which is recognized by both substance P (1-11) and substance P (1-7) rather than the tachykinin receptor, is involved in NPFF secretion from the spinal cord. In view of the role of substance P (1-11) and substance P (1-7) in sensory transmission, the results of this study further support the role of NPFF in the modulation of antinociception in the spinal cord. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,BIOCHEM GENET LAB,WASHINGTON,DC 20032. QUEENS UNIV,DEPT PHARMACOL & TOXICOL,KINGSTON K7L 3N6,ONTARIO,CANADA. NR 28 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 2 PY 1992 VL 592 IS 1-2 BP 326 EP 332 DI 10.1016/0006-8993(92)91692-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA JR759 UT WOS:A1992JR75900042 PM 1280519 ER PT J AU CLARK, DJ FELSENFELD, G AF CLARK, DJ FELSENFELD, G TI A NUCLEOSOME CORE IS TRANSFERRED OUT OF THE PATH OF A TRANSCRIBING POLYMERASE SO CELL LA English DT Article ID RNA-POLYMERASE; TRANSCRIPTIONALLY COMPETENT; CHROMATIN STRUCTURE; DNA-TEMPLATE; II INVITRO; 5S RNA; INITIATION; HISTONES; DISPLACEMENT; ELONGATION AB We have determined the fate of a nucleosome core on transcription. A nucleosome core was assembled on a short DNA fragment and ligated into a plasmid containing a promoter and terminators for SP6 RNA polymerase. The nucleosome core was stable in the absence of transcription. The distribution of nucleosome cores after transcription was examined. The histone octamer was displaced from its original site and reformed a nucleosome core at a new site within the same plasmid molecule, with some preference for the untranscribed region behind the promoter. These observations eliminate several models that have been proposed for transcription through a nucleosome core. Our results suggest that a nucleosome core in the path of a transcribing polymerase is displaced by transfer to the closest acceptor DNA. RP CLARK, DJ (reprint author), NIH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 48 TC 115 Z9 115 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 2 PY 1992 VL 71 IS 1 BP 11 EP 22 DI 10.1016/0092-8674(92)90262-B PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JQ623 UT WOS:A1992JQ62300003 PM 1394427 ER PT J AU SPRIGGS, MK HRUBY, DE MALISZEWSKI, CR PICKUP, DJ SIMS, JE BULLER, RML VANSLYKE, J AF SPRIGGS, MK HRUBY, DE MALISZEWSKI, CR PICKUP, DJ SIMS, JE BULLER, RML VANSLYKE, J TI VACCINIA AND COWPOX VIRUSES ENCODE A NOVEL SECRETED INTERLEUKIN-1-BINDING PROTEIN SO CELL LA English DT Article ID INVERTED TERMINAL REPEAT; EPIDERMAL GROWTH-FACTOR; OPEN READING FRAME; B-CELL GROWTH; IMMUNOGLOBULIN SUPERFAMILY; EXPRESSION VECTORS; INFLUENZA-VIRUS; IL-1 RECEPTOR; T-CELLS; INFECTION AB Supernatants from vaccinia virus (VV)-infected CV-1 cells were examined and found to contain a 33 kd protein capable of binding murine interleukin-1beta (mIL-1beta). A VV open reading frame (ORF) that exhibits 30% amino acid identity to the type II IL-1 receptor was expressed in CV-1-EBNA cells and shown specifically to bind mIL-1beta. A similar ORF from cowpox virus was expressed and also specifically bound mIL-1beta. A recombinant VV was constructed in which this ORF was disrupted (vB15RKO). Supernatants from vB15RKO-infected cells did not contain an IL-1-binding protein. Supernatants from VV-infected CV-1 cells were capable of inhibiting IL-1-induced murine lymphocyte proliferation in vitro while supernatants from vB15RKO infected cells did not. Intracranial inoculation of mice with vB15RKO suggests that this ORF is involved in VV virulence. The possible role of a virus-encoded IL-1-binding protein in the pathology of a poxvirus infection and its relationship to other poxvirus-encoded immune modulators is discussed. C1 IMMUNEX RES & DEV CORP,DEPT IMMUNOL,SEATTLE,WA 98101. OREGON STATE UNIV,DEPT MICROBIOL,CORVALLIS,OR 97331. DUKE UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,DURHAM,NC 27710. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP SPRIGGS, MK (reprint author), IMMUNEX RES & DEV CORP,DEPT MOLEC BIOL,SEATTLE,WA 98101, USA. FU NIAID NIH HHS [AI21335-06] NR 53 TC 274 Z9 276 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 2 PY 1992 VL 71 IS 1 BP 145 EP 152 DI 10.1016/0092-8674(92)90273-F PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JQ623 UT WOS:A1992JQ62300014 PM 1339315 ER PT J AU GUYER, M AF GUYER, M TI A COMPREHENSIVE GENETIC-LINKAGE MAP OF THE HUMAN GENOME SO SCIENCE LA English DT Article ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; DOMINANT RETINITIS-PIGMENTOSA; CYSTIC-FIBROSIS GENE; NEUROFIBROMATOSIS TYPE-1 GENE; FRAGMENT LENGTH POLYMORPHISMS; LONG ARM; DINUCLEOTIDE REPEAT; HUMAN CHROMOSOME-16; DNA MARKERS; ADENOMATOUS POLYPOSIS AB A genetic linkage map of the human genome was constructed that consists of 1416 loci, including 279 genes and expressed sequences. The loci are represented by 1676 polymorphic systems genotyped with the CEPH reference pedigree resource. A total of 339 microsatellite repeat markers assayed by PCR are contained within the map, and of the 351 markers with heterozygosities of at least 70%, 205 are microsatellites. Seven telomere loci define physical and genetic endpoints for 2q, 4p, 7q, 8p, 14q, 16p, and 16q, and in other cases distal markers on the maps have been localized to terminal cytogenetic bands. Therefore, at least 92% of the autosomal length of the genome and 95% of the X chromosome is estimated to be spanned by the map. Since the maps have relatively high marker density and numerous highly informative loci, they can be used to map disease phenotypes, even for those with limited pedigree resources. The baseline map provides a foundation for achieving continuity of clone-based physical maps and for the development of a truly integrated physical, genetic, and cytogenetic map of the human. RP GUYER, M (reprint author), NIH,NCHGR BLDG,38A,ROOM 605,BETHESDA,MD 20892, USA. RI Haines, Jonathan/C-3374-2012 NR 144 TC 112 Z9 115 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 2 PY 1992 VL 258 IS 5079 BP 67 EP 86 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ619 UT WOS:A1992JQ61900026 ER PT J AU FARCI, P ALTER, HJ GOVINDARAJAN, S WONG, DC ENGLE, R LESNIEWSKI, RR MUSHAHWAR, IK DESAI, SM MILLER, RH OGATA, N PURCELL, RH AF FARCI, P ALTER, HJ GOVINDARAJAN, S WONG, DC ENGLE, R LESNIEWSKI, RR MUSHAHWAR, IK DESAI, SM MILLER, RH OGATA, N PURCELL, RH TI LACK OF PROTECTIVE IMMUNITY AGAINST REINFECTION WITH HEPATITIS-C VIRUS SO SCIENCE LA English DT Article ID NON-B-HEPATITIS; EXPERIMENTALLY INFECTED CHIMPANZEES; TRANSFUSION-ASSOCIATED HEPATITIS; NON-A-HEPATITIS; VIRAL-HEPATITIS; ENVELOPE PROTEIN; LONG-TERM; POSTTRANSFUSION HEPATITIS; CROSS-CHALLENGE; HUMAN CARRIERS AB Some individuals infected with hepatitis C virus (HCV) experience multiple episodes of acute hepatitis. It is unclear whether these episodes are due to reinfection with HCV or to reactivation of the original virus infection. Markers of viral replication and host immunity were studied in five chimpanzees sequentially inoculated over a period of 3 years with different HCV strains of proven infectivity. Each rechallenge of a convalescent chimpanzee with the same or a different HCV strain resulted in the reappearance of viremia, which was due to infection with the subsequent challenge virus. The evidence indicates that HCV infection does not elicit protective immunity against reinfection with homologous or heterologous strains, which raises concerns for the development of effective vaccines against HCV. C1 NIH,WARREN G MARGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RANCHO LOS AMIGOS MED CTR,DOWNEY,CA 90242. GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. ABBOTT LABS,EXPTL BIOL RES,N CHICAGO,IL 60064. RP FARCI, P (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 64 TC 633 Z9 637 U1 1 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 2 PY 1992 VL 258 IS 5079 BP 135 EP 140 DI 10.1126/science.1279801 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ619 UT WOS:A1992JQ61900036 PM 1279801 ER PT J AU HONG, X MERRIL, CR POLYMEROPOULOS, MH AF HONG, X MERRIL, CR POLYMEROPOULOS, MH TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D7S476 LOCUS SO HUMAN MOLECULAR GENETICS LA English DT Note C1 ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, WASHINGTON, DC 20032 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1992 VL 1 IS 7 BP 549 EP 549 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JV142 UT WOS:A1992JV14200019 ER PT J AU TSAI, WP KUNG, HF GOUDSMIT, J RIMMELZWAAN, G MINASSIAN, A GARRITY, R NARA, P AF TSAI, WP KUNG, HF GOUDSMIT, J RIMMELZWAAN, G MINASSIAN, A GARRITY, R NARA, P TI HIV-1 TROPISM - TRUTH OR CONSEQUENCES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-1; SOLUBLE CD4; CELL-CULTURE; INFECTION; GP120; SUSCEPTIBILITY; NEUTRALIZATION; LYMPHOCYTES; RECEPTOR; AFFINITY C1 UNIV AMSTERDAM,ACAD MED CTR,DEPT VIROL,HUMAN RETROVIRUS LAB,1105 AZ AMSTERDAM,NETHERLANDS. DYNACORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,DIV CANC ETIOL,BIOL CARCINOGENESIS PROGRAM,FREDERICK,MD 21702. RP TSAI, WP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 31 TC 6 Z9 6 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 OCT PY 1992 VL 8 IS 10 BP 1749 EP 1750 DI 10.1089/aid.1992.8.1749 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA JX139 UT WOS:A1992JX13900003 PM 1457187 ER PT J AU HUANG, CM ELIN, RJ RUDDEL, M SCHMITZ, J LINNOILA, M AF HUANG, CM ELIN, RJ RUDDEL, M SCHMITZ, J LINNOILA, M TI THE EFFECT OF ALCOHOL-WITHDRAWAL ON SERUM CONCENTRATIONS OF LP(A), APOLIPOPROTEIN-A-I AND APOLIPOPROTEIN-B, AND LIPIDS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE LP(A); APOLIPOPROTEIN-A-I; APOLIPOPROTEIN-B; SERUM LIPIDS ID DENSITY LIPOPROTEIN CHOLESTEROL; CORONARY-ARTERY DISEASE; ISCHEMIC HEART-DISEASE; A-I; MYOCARDIAL-INFARCTION; PLASMA; CONSUMPTION; SUBFRACTIONS; PHENOTYPES; METABOLISM AB Moderate alcohol consumption is associated with a decreased risk of coronary artery disease. The mechanism of the putative protective effect of alcohol intake, however, remains elusive. Recent studies suggest that a ratio of apolipoprotein A-I/apolipoprotein B and Lp(a) are better indicators of the risk of atherosclerosis than total cholesterol and high density lipoprotein cholesterol. To assess the effect of alcohol on these analytes, we determined the concentration of Lp(a), apolipoprotein A-I, apolipoprotein B, total cholesterol, and high-density lipoprotein cholesterol, and calculated low-density lipoprotein cholesterol in serum of 12 patients meeting DSM-III-R criteria for alcohol dependence at the time of admission for treatment of alcohol withdrawal (before). The analyses were repeated after 4 weeks of supervised abstinence on a locked research unit (after). With abstinence, there was a significant increase in the concentration of Lp(a), the atherogenic index and the ratio of low-density to high-density lipoprotein cholesterol but a significant decrease in total cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I, and the apolipoprotein A-I/B ratio. Apolipoprotein B and low-density lipoprotein cholesterol showed no significant changes before and after alcohol abstinence. Thus, decreased Lp(a) and increased high-density lipoprotein cholesterol and apolipoprotein A-I may be factors mediating the putative protective effect of alcohol in coronary artery disease. C1 NIH,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 2C-306,BETHESDA,MD 20892. NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD. NR 31 TC 31 Z9 31 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 OCT PY 1992 VL 16 IS 5 BP 895 EP 898 DI 10.1111/j.1530-0277.1992.tb01889.x PG 4 WC Substance Abuse SC Substance Abuse GA JU899 UT WOS:A1992JU89900013 PM 1332524 ER PT J AU PIROZHKOV, SV ESKELSON, CD WATSON, RR AF PIROZHKOV, SV ESKELSON, CD WATSON, RR TI CHRONIC ETHANOL AND COCAINE-INDUCED HEPATOTOXICITY - EFFECTS OF VITAMIN-E SUPPLEMENTATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE HEPATOTOXICITY; ETHANOL; COCAINE; LIPID PEROXIDATION; VITAMIN-E ID INDUCED HEPATIC-NECROSIS; LIPID-PEROXIDATION; NORCOCAINE NITROXIDE; REACTIVE METABOLITES; N-HYDROXYNORCOCAINE; STRAIN DIFFERENCES; RAT-LIVER; MICE; ANTIOXIDANT; INJURY AB The mechanisms of chronic cocaine toxicity and its potentiation by ethanol were investigated. Cocaine was administered to male C57BL/6 mice (20 mg/kg by peritoneal injection twice a day) alone or in combination with ethanol-containing diets (26% of total calories) supplied with a normal (20 IU/liter) or high content (170 IU/liter) of vitamin E. Liver levels of vitamin E, reduced glutathione, ascorbic acid, and hydroxyproline were measured. Accumulation of thiobarbituric acid-reactive substances, after in vitro stimulation of lipid peroxidation by Fe3+/ADP/ascorbate system, was measured as an index of susceptibility of hepatic membranes to oxidative stress. Plasma alanine aminotransferase, lethality, liver weight, and liver/body weight ratio were determined to assess the extent of liver toxicity. Consumption of ethanol exacerbated liver toxicity induced by cocaine treatments and reduced survival, but ethanol or cocaine treatments alone caused no or only modest mortality. Ethanol potentiated cocaine-induced accumulation of collagen in the liver and depletion of ascorbic acid. Hepatotoxicity induced by the combined ethanol plus cocaine treatment was not accompanied by a decrease in intracellular vitamin E or glutathione content. There were no changes in the basic levels and in the rate of accumulation of thiobarbituric acid-reactive substances in liver homogenates under the lipid peroxidation-stimulating system in vitro. The toxic effects of ethanol and cocaine were not reduced by the ingestion of vitamin E during short-term exposure of 21 days of treatment. C1 UNIV ARIZONA,ARIZONA HLTH SCI CTR,NATL INST ALCOHOL ABUSE & ALCOHOLISM,TUCSON,AZ 85724. MOSCOW MEDICOBIOL PROBLEMS ADDICT RES INST,MOSCOW,USSR. RP WATSON, RR (reprint author), UNIV ARIZONA,ARIZONA HLTH SCI CTR,NATL INST ALCOHOL ABUSE & ALCOHOLISM,TUCSON,AZ 85724, USA. FU NIAAA NIH HHS [AA08037] NR 48 TC 8 Z9 8 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 OCT PY 1992 VL 16 IS 5 BP 904 EP 909 DI 10.1111/j.1530-0277.1992.tb01891.x PG 6 WC Substance Abuse SC Substance Abuse GA JU899 UT WOS:A1992JU89900015 PM 1443428 ER PT J AU SHIRANI, J ROBERTS, WC AF SHIRANI, J ROBERTS, WC TI ORIGIN OF THE LEFT MAIN CORONARY-ARTERY FROM THE RIGHT AORTIC SINUS WITH RETROAORTIC COURSE OF THE ANOMALISTICALLY ARISING ARTERY SO AMERICAN HEART JOURNAL LA English DT Note RP SHIRANI, J (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 1992 VL 124 IS 4 BP 1077 EP 1078 DI 10.1016/0002-8703(92)90995-8 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JQ688 UT WOS:A1992JQ68800034 PM 1529883 ER PT J AU JOHNSTONE, D LIMACHER, M ROUSSEAU, M LIANG, CS EKELUND, L HERMAN, M STEWART, D GUILLOTTE, M BJERKEN, G GAASCH, W HELD, P VERTER, J STEWART, D YUSUF, S AF JOHNSTONE, D LIMACHER, M ROUSSEAU, M LIANG, CS EKELUND, L HERMAN, M STEWART, D GUILLOTTE, M BJERKEN, G GAASCH, W HELD, P VERTER, J STEWART, D YUSUF, S TI CLINICAL CHARACTERISTICS OF PATIENTS IN STUDIES OF LEFT-VENTRICULAR DYSFUNCTION (SOLVD) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; EJECTION FRACTION; RISK; POPULATION; ADVANTAGES; DISEASE; WOMEN AB The Studies of Left Ventricular Dysfunction (SOLVD) trials were designed to evaluate the ef fects of enalapril on long-term mortality in patients with severe left ventricular (LV) dysfunction. Patients with LV ejection fractions less-than-or-equal-to 0.35 and symptoms of congestive heart failure (CHF were enrolled in the treatment trial, whereas those with no history of overt CHF and taking no treat ment directed for L.V dysfunction were enrolled in the prevention trial. The baseline clinical characteristics of SOLVD patients were compared to characterize differences between patients in these 2 separate but concurrent trials. From over 70,000 patients screened with LV dysfunction, 4,228 patients were enrolled in the prevention trial and 2,569 patients in the treatment trial. Ischemic heart disease was the primary cause of LV dysfunction in both prevention (83%) and treatment (71%) trial patients. Prior myocardial infarction was present in 80% of the prevention and 66% of the treatment trial patients (p < 0.001). In the prevention trial, infarction was recent (less-than-or-equal-to 6 months) in 27% patients and remote (> 6 months) in 57% patients. Treatment trial patients had proportionately more women (20 vs 13%; p < 0.001), as and non-Caucasians (20 vs 14%; p < 0.001) as well as the coexisting risk factors of hypertension (42 vs 37%; p < 0.001) and diabetes (26 vs p < 0.001) than did prevention trial patients. Treatment trial patients were more likely to have the clinical signs associated with CHF and had a lower mean LV ejection fraction (0.25 +/- 0.07 vs 0.28 +/- 0.06, p < 0.001)) than prevention trial patients. Clinical characteristics of patients in both trials were influenced by the gender and race of enrolled patients. Similarly, coronary artery by. pass surgery was performed less often in women and non-Caucasians. Thus, the baseline database of patients enrolled in the SOLVD trials demonstrates the varied clinical features associated with severe LV dysfunction and highlights the impact of symptomatic status, gender and race on clinical presentation. C1 NHLBI, DIV EPIDEMIOL,FED BLDG,ROOM 5C10, 7550 WISCONSIN AVE, BETHESDA, MD 20892 USA. NHLBI, CLIN APPLICAT CLIN TRIALS BRANCH, BETHESDA, MD 20892 USA. NR 20 TC 68 Z9 70 U1 1 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 1992 VL 70 IS 9 BP 894 EP 900 DI 10.1016/0002-9149(92)90734-G PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JP600 UT WOS:A1992JP60000011 PM 1529944 ER PT J AU ENAS, EA YUSUF, S MEHTA, JL AF ENAS, EA YUSUF, S MEHTA, JL TI PREVALENCE OF CORONARY-ARTERY DISEASE IN ASIAN INDIANS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID DENSITY LIPOPROTEIN CHOLESTEROL; ISCHEMIC-HEART-DISEASE; MONOUNSATURATED FATTY-ACIDS; RISK-FACTORS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; GLUCOSE-INTOLERANCE; INSULIN RESISTANCE; WHITE MEN; FRAMINGHAM C1 CORONARY ARTERY DIS AMONG INDIANS STUDY,WOODRIDGE,IL. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,BETHESDA,MD 20892. UNIV FLORIDA,COLL MED,DIV CARDIOL,GAINESVILLE,FL 32611. VET ADM MED CTR,GAINESVILLE,FL 32602. NR 63 TC 142 Z9 147 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 1992 VL 70 IS 9 BP 945 EP 949 DI 10.1016/0002-9149(92)90744-J PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JP600 UT WOS:A1992JP60000021 PM 1529952 ER PT J AU HOAK, JC SPECTOR, AA AF HOAK, JC SPECTOR, AA TI WORKSHOP ON DIETARY FATTY-ACIDS AND THROMBOSIS - OVERVIEW SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material C1 UNIV IOWA, DEPT BIOCHEM, IOWA CITY, IA 52242 USA. RP NHLBI, DIV BLOOD DIS & RESOURCES, ROOM 516 FED BLDG, 7550 WISCONSINE AVE, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1992 VL 56 IS 4 SU S BP 783 EP 784 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JV008 UT WOS:A1992JV00800001 ER PT J AU HOAK, JC AF HOAK, JC TI WHAT IS THE HISTORICAL BACKGROUND OF RESEARCH ON THE ROLE OF FATTY-ACIDS IN THROMBOSIS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID DIETARY RP NHLBI, DIV BLOOD DIS & RESOURCES, ROOM 516 FED BLDG, 7550 WISCONSIN AVE, BETHESDA, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1992 VL 56 IS 4 SU S BP 786 EP 786 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA JV008 UT WOS:A1992JV00800003 ER PT J AU MEDEIROS, LJ STETLERSTEVENSON, M AF MEDEIROS, LJ STETLERSTEVENSON, M TI COMPOSITE B-CELL AND T-CELL LYMPHOMA - COINCIDENTAL OCCURRENCE OR RELATED NEOPLASMS SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; IMMUNOGLOBULIN LIGHT-CHAINS; RICHTERS SYNDROME; CLONAL ORIGIN; PATIENT C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. RP MEDEIROS, LJ (reprint author), RHODE ISL HOSP,DEPT PATHOL,PROVIDENCE,RI 02902, USA. NR 20 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 1992 VL 98 IS 4 BP 387 EP 389 PG 3 WC Pathology SC Pathology GA JU018 UT WOS:A1992JU01800001 PM 1415019 ER PT J AU SIDRANSKY, E TSUJI, S STUBBLEFIELD, B MARTIN, B GINNS, EI AF SIDRANSKY, E TSUJI, S STUBBLEFIELD, B MARTIN, B GINNS, EI TI MUTATION ANALYSIS IN GAUCHER DISEASE SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter RP SIDRANSKY, E (reprint author), NIMH,DEPT HLTH & HUMAN SERV,CLIN GENET UNIT,SECT MOLEC NEUROGENET,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 1 PY 1992 VL 44 IS 3 BP 390 EP 390 DI 10.1002/ajmg.1320440329 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA JR909 UT WOS:A1992JR90900028 ER PT J AU ROMERO, R SEPULVEDA, W MAZOR, M BRANDT, F COTTON, DB DINARELLO, CA MITCHELL, MD AF ROMERO, R SEPULVEDA, W MAZOR, M BRANDT, F COTTON, DB DINARELLO, CA MITCHELL, MD TI THE NATURAL INTERLEUKIN-1 RECEPTOR ANTAGONIST IN TERM AND PRETERM PARTURITION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 12TH ANNUAL MEETING OF THE SOC OF PERINATAL OBSTETRICIANS CY FEB 03-08, 1992 CL ORLANDO, FL SP SOC PERINATAL OBSTETRICIANS DE INTERLEUKIN-1 RECEPTOR ANTAGONIST; PRETERM LABOR; AMNIOTIC FLUID; INTRAAMNIOTIC INFECTION ID BLOOD MONONUCLEAR-CELLS; PROSTAGLANDIN BIOSYNTHESIS; INFLAMMATORY MEDIATORS; EXPRESSION; INVITRO; MEMBER; FAMILY; LABOR AB OBJECTIVE: Interleukin-1 has been implicated in the mechanisms responsible for preterm labor in the setting of infection. The interleukin-1 receptor antagonist is a new member of the interleukin-1 gene family that inhibits the biologic effects of interleukin-1 by blocking its receptors. Reduction of interleukin-1-induced prostaglandin production by intrauterine tissues may have potential value in the treatment of preterm labor associated with infection. The purpose of these studies was (1) to determine interleukin-1 receptor antagonist levels in the amniotic fluid of women with term and preterm labor (with and without infection) and (2) to study the effects of interleukin-1 receptor antagonist on interleukin-1-induced prostaglandin biosynthesis by human amnion and chorion. STUDY DESIGN: Amniotic fluid was obtained from women in the midtrimester of pregnancy (n = 20), at term pregnancy (with and without labor, n = 69), and in preterm labor (n = 47). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Interleukin-1alpha, interleukin-1beta, and interleukin-1 receptor antagonist concentrations were measured by immunoassays previously validated for human amniotic fluid. The effect of interleukin-1 receptor antagonist on interleukin-1-induced prostaglandin production by amnion and chorion was studied with primary cultures. Cells were incubated with interleukin-1 receptor antagonist and interleukin-1alpha or interleukin-1beta for 16 hours. Prostaglandin E2 released into the media was assayed by immunoassay. RESULTS: (1) Interleukin-1 receptor antagonist was present in all amniotic fluid samples; (2) amniotic fluid contains the highest interleukin-1 receptor antagonist concentrations detected in any biologic fluid to date; (3) amniotic fluid interleukin-1 receptor antagonist concentrations were not increased in women with preterm labor and intraamniotic infection in spite of dramatically elevated concentrations of interleukin-1alpha and interleukin-1beta in the same fluid (median 22 ng/ml and range 0.16 to 70 for preterm labor with negative amniotic fluid culture vs median 30 ng/ml and range 6 to 70 for preterm labor with positive amniotic fluid culture; p > 0.05); (4) interleukin-1 receptor antagonist reduced interleukin-1beta-induced prostaglandin E2 production by amnion and chorion in a dose-dependent manner; (5) interleukin-1 receptor antagonist by itself did not stimulate prostaglandin E2 release by amnion and chorion when used in concentrations ranging from 0.1 to 1000 ng/ml. C1 TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111. YALE UNIV,SCH MED,DEPT OBSTET & GYNECOL,NEW HAVEN,CT 06510. UNIV UTAH,MED CTR,DEPT OBSTET & GYNECOL,SALT LAKE CITY,UT 84112. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RP ROMERO, R (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. RI Mitchell, Murray/A-8639-2010 OI Mitchell, Murray/0000-0002-6167-7176 FU NIAID NIH HHS [AI 15614] NR 25 TC 106 Z9 106 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1992 VL 167 IS 4 BP 863 EP 872 PN 1 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JU065 UT WOS:A1992JU06500001 PM 1415417 ER PT J AU ROMERO, R TARTAKOVSKY, B AF ROMERO, R TARTAKOVSKY, B TI THE NATURAL INTERLEUKIN-1 RECEPTOR ANTAGONIST PREVENTS INTERLEUKIN-1-INDUCED PRETERM DELIVERY IN MICE SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 12TH ANNUAL MEETING OF THE SOC OF PERINATAL OBSTETRICIANS CY FEB 03-08, 1992 CL ORLANDO, FL SP SOC PERINATAL OBSTETRICIANS DE INTERLEUKIN-1; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PRETERM LABOR; PREMATURITY; CHORIOAMNIONITIS ID PROSTAGLANDIN BIOSYNTHESIS; DECIDUAL CELLS; HUMAN AMNION; EXPRESSION; ENDOTOXIN; PARTURITION; SHOCK AB OBJECTIVES: Interleukin-1 has been implicated in the mechanisms responsible for preterm parturition in the setting of intrauterine infection. This cytokine is produced by human decidua, stimulates prostaglandin production by intrauterine tissues, and induces preterm parturition in mice. The purpose of this study was to determine whether pretreatment with the natural interleukin-1 receptor antagonist can block interleukin-1-induced preterm parturition in mice. STUDY DESIGN: Balb/CJ female mice impregnated by B6D2 F-1 male mice were randomly allocated to one of the following treatment groups: (1) saline solution (n = 15), (2) human recombinant interleukin-1alpha or human recombinant interleukin-1beta (n = 12), (3) human recombinant interleukin-1 receptor antagonist (n = 13), and (4) human recombinant interleukin-1 receptor antagonist plus human recombinant interleukin-1 (n = 24). RESULTS: An interleukin-1 dose of 10 mug per mouse induced preterm parturition in all cases. Pretreatment with interleukin-1 receptor antagonist (dose 1 mg per animal) prevented interleukin-1-induced preterm parturition. Interleukin-1 receptor antagonist administration was not associated with demonstrable side effects including behavioral changes, vaginal bleeding, duration of pregnancy, and pregnancy outcome. CONCLUSION: Our results suggest that interleukin-1-induced preterm delivery in mice is mediated by the interleukin-1 receptor. C1 NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. RP ROMERO, R (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. NR 25 TC 151 Z9 151 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1992 VL 167 IS 4 BP 1041 EP 1045 PN 1 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JU065 UT WOS:A1992JU06500033 PM 1415389 ER PT J AU ROMERO, R GONZALEZ, R SEPULVEDA, W BRANDT, F RAMIREZ, M SOROKIN, Y MAZOR, M TREADWELL, MC COTTON, DB AF ROMERO, R GONZALEZ, R SEPULVEDA, W BRANDT, F RAMIREZ, M SOROKIN, Y MAZOR, M TREADWELL, MC COTTON, DB TI INFECTION AND LABOR .8. MICROBIAL INVASION OF THE AMNIOTIC CAVITY IN PATIENTS WITH SUSPECTED CERVICAL INCOMPETENCE - PREVALENCE AND CLINICAL-SIGNIFICANCE SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 12TH ANNUAL MEETING OF THE SOC OF PERINATAL OBSTETRICIANS CY FEB 03-08, 1992 CL ORLANDO, FL SP SOC PERINATAL OBSTETRICIANS DE AMNIOTIC FLUID CULTURE; CHORIOAMNIONITIS; RUPTURE OF MEMBRANES; CERVICAL CERCLAGE; CERVICAL INCOMPETENCE; SPONTANEOUS 2ND-TRIMESTER ABORTION ID INTRAAMNIOTIC INFECTION; FETAL MEMBRANES; PRETERM LABOR; CERCLAGE; CHORIOAMNIONITIS; GESTATION; WOMEN AB OBJECTIVE: The purpose of this study was to determine the prevalence and clinical significance of microbial invasion of the amniotic cavity in patients presenting with cervical dilatation in the midtrimester of pregnancy. STUDY DESIGN: Amniocentesis for microbial studies was performed in women admitted with cervical dilatation greater-than-or-equal-to 2 cm, intact membranes, and without active labor between 14 and 24 weeks of gestation. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Gram stain was performed on all samples. RESULTS: The prevalence of microbial invasion of the amniotic cavity was 51.5% (17/33). The most common microbial isolates were Ureaplasma urealyticum, Gardnerella vaginalis, Candida albicans, and Fusobacterium sp. All patients with microbial invasion of the amniotic cavity had complications. Patients who underwent cervical cerclage in the presence of a positive amniotic fluid culture had rupture of membranes, clinical chorioamnionitis, or pregnancy loss. On the other hand, the prognosis of patients with a negative amniotic fluid culture was better than that of patients with a positive culture. Of 16 patients with a negative amniotic culture, nine were delivered at >34 weeks. CONCLUSIONS: (1) Microbial invasion of the amniotic cavity occurs frequently in women presenting with cervical dilatation in the midtrimester; (2) the microbiologic state of the amniotic cavity is an important prognostic factor for pregnancy outcome; (3) amniocentesis to determine the microbiologic characteristics of the amniotic cavity should be considered before a cerclage is placed in women presenting with cervical dilatation in the midtrimester. C1 YALE UNIV,SCH MED,DEPT OBSTET & GYNECOL,NEW HAVEN,CT 06510. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RP ROMERO, R (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. NR 30 TC 125 Z9 129 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1992 VL 167 IS 4 BP 1086 EP 1091 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JU065 UT WOS:A1992JU06500041 PM 1415396 ER PT J AU BUEE, L HOF, PR ROBERTS, DD DELACOURTE, A MORRISON, JH FILLIT, HM AF BUEE, L HOF, PR ROBERTS, DD DELACOURTE, A MORRISON, JH FILLIT, HM TI IMMUNOHISTOCHEMICAL IDENTIFICATION OF THROMBOSPONDIN IN NORMAL HUMAN BRAIN AND IN ALZHEIMERS-DISEASE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID HUMAN-MELANOMA CELLS; PLATELET THROMBOSPONDIN; NEURITE OUTGROWTH; SENILE DEMENTIA; NEURONS; CORTEX; PROTEOGLYCANS; ANGIOGENESIS; ANTIBODIES; IMPAIRMENT AB Thrombospondin is part of a family of adhesive glycoproteins and is involved in a number of physiologic processes such as angiogenesis and neurite out-growth. Immunohistochemical localization of thrombospondin in normal human brains was investigated in the hippocampus and inferior temporal cortex. Two antibodies (one polyclonal and one monoclonal) against thrombospondin-labeled microvessels, glial cells, and a subpopulation of pyramidal neurons. The distribution of thrombospondin staining in patients with Alzheimer's disease was found to be comparable to control subjects. However, in patients with Alzheimer's disease a subset of pyramidal neurons that may be vulnerable in Alzheimer's disease exhibited decreased staining. This decrease in the intensity of labeling might constitute a marker for a neuronal population prone to early degeneration. In addition, thrombospondin staining was demonstrated in senile plaques in Alzheimer's disease. These results suggest that thrombospondin may be involved in the process of neuronal degeneration and senile plaque formation. C1 CUNY MT SINAI SCH MED,DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,FISHBERG RES CTR NEUROBIOL,NEW YORK,NY 10029. NCI,PATHOL LAB,BETHESDA,MD 20892. INSERM,U156,F-59045 LILLE,FRANCE. RI Roberts, David/A-9699-2008; Morrison, John/F-9229-2012; BUEE, Luc/B-3126-2010 OI Roberts, David/0000-0002-2481-2981; BUEE, Luc/0000-0002-6261-4230 FU NIA NIH HHS [AG 06647, AG 05138] NR 33 TC 53 Z9 53 U1 3 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1992 VL 141 IS 4 BP 783 EP 788 PG 6 WC Pathology SC Pathology GA JR554 UT WOS:A1992JR55400004 PM 1415477 ER PT J AU WARD, JM STEVENS, JL KONISHI, N KURATA, Y UNO, H DIWAN, BA OHMORI, T AF WARD, JM STEVENS, JL KONISHI, N KURATA, Y UNO, H DIWAN, BA OHMORI, T TI VIMENTIN METAPLASIA IN RENAL CORTICAL TUBULES OF PRENEOPLASTIC, NEOPLASTIC, AGING, AND REGENERATIVE LESIONS OF RATS AND HUMANS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INTERMEDIATE FILAMENT PROTEINS; MONOCLONAL-ANTIBODIES; BARBITAL SODIUM; F344/NCR RATS; DNA-SYNTHESIS; KIDNEY; TUMORS; TISSUE; EXPRESSION; ENHANCEMENT AB Vimentin expression was studied immunohistochemically in renal cortical tubules of untreated male rats of various ages rats exposed to toxins (barbital sodium, folk acid) and carcinogens (streptozotocin, N-bis(2-hydroxypropyl)nitrosamine, barbital sodium, and in humans of various ages with or without renal epithelial tumors. Fetal, neonatal, and young adult rats did not express vimentin in renal cortical tubules. Regenerative renal tubular lesions from rats with aging nephropathy and from rats with toxic nephropathy both expressed vimentin. Mitogenic lesions induced by folk acid at 24 hours, however, were not immunoreactive for vimentin. Carcinogen-induced preneoplastic renal cortical tubular lesions in rats were most often focally immunoreactive whereas strong vimentin expression was found in almost all induced renal tumors. In kidneys of three children (younger than 2 years of age), vimentin was not found in renal cortical tubular cells except in rare individual cells in one case. Vimentin was abundant in basophilic regenerative tubules in kidneys of aged individuals, however. Most (7/10) human renal carcinomas and latent preneoplastic or neoplastic renal tubular lesions found incidentally at autopsy (2/4) showed vimentin expression. The authors suggest that the switching to vimentin expression in phenotypically normal renal cortical tubular cells in rats and humans, which do not usually express the intermediate filament protein vimentin, should be considered vimentin metaplasia. Vimentin expression is dissociated from increased cell proliferation in hyperplastic and neoplastic lesions, however, Instead the degree of dedifferentiation of the tubule cells and changes in phenotype were associated with vimentin expression. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. W ALTON JONES CELL SCI CTR,LAKE PLACID,NY 12946. NARA MED UNIV,DEPT PATHOL 1,KASHIHARA,NARA 634,JAPAN. EHIME UNIV,SCH MED,DEPT PATHOL,MATSUYAMA,EHIME 790,JAPAN. RP WARD, JM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,TUMOR PATHOL & PATHOGENESIS SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [CA 38925, N01-CO-74102]; NIEHS NIH HHS [ES05670] NR 44 TC 49 Z9 50 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1992 VL 141 IS 4 BP 955 EP 964 PG 10 WC Pathology SC Pathology GA JR554 UT WOS:A1992JR55400022 PM 1415487 ER PT J AU RISING, R KEYS, A RAVUSSIN, E BOGARDUS, C AF RISING, R KEYS, A RAVUSSIN, E BOGARDUS, C TI CONCOMITANT INTERINDIVIDUAL VARIATION IN BODY-TEMPERATURE AND METABOLIC-RATE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ENERGY EXPENDITURE; OBESITY; REGULATION ID ENERGY-EXPENDITURE; OBESITY; WEIGHT; RISK AB There is significant variation in metabolic rate in humans, independent of differences in body size, body composition, age, and gender. Although it has been generally held that the normal human "set-point" body temperature is 37-degrees-C, these interindividual variations in metabolic rate also suggest possible variations in body temperature. To examine the possibility of correlations between metabolic rate and body temperature, triplicate measurements of oral temperatures were made before and after measurement of 24-h energy expenditure in a respiratory chamber in 23 Pima Indian men. Fasting oral temperatures varied more between individuals than can be attributed to methodological errors or intraindividual variation. Oral temperatures correlated with sleeping (r = 0.80, P < 0.0001), and 24-h (r = 0.48, P < 0.02) metabolic rates adjusted for differences in body size, body composition, and age. Similarly, in the 32 Caucasian men of the Minnesota Semi-Starvation Study, oral temperature correlated with adjusted metabolic rate, and the interindividual differences in body temperature were maintained throughout semistarvation and refeeding. These results suggest that a low body temperature and a low metabolic rate might be two signs of an obesity-prone syndrome in humans. RP RISING, R (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,RM 541,PHOENIX,AZ 85016, USA. NR 15 TC 54 Z9 56 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1992 VL 263 IS 4 BP E730 EP E734 PN 1 PG 5 WC Physiology SC Physiology GA JU805 UT WOS:A1992JU80500044 PM 1415692 ER PT J AU BRACHA, HS TORREY, EF GOTTESMAN, II BIGELOW, LB CUNNIFF, C AF BRACHA, HS TORREY, EF GOTTESMAN, II BIGELOW, LB CUNNIFF, C TI 2ND-TRIMESTER MARKERS OF FETAL SIZE IN SCHIZOPHRENIA - A STUDY OF MONOZYGOTIC TWINS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FLUCTUATING DERMATOGLYPHIC ASYMMETRY; PSYCHOTIC TWINS; DISCORDANT AB Objective: Since the second prenatal trimester is the critical period of massive neural cell migration to the cortex, and fingertip dermal cells migrate to form ridges during this same period, the authors sought to determine whether there are differences in fingertip ridge count in pairs of monozygotic twins discordant for schizophrenia, possibly indicating that a prenatal anatomical insult affected the twins differently. Method: The fingertip dermal ridges of 30 pairs of monozygotic twins (23 pairs in which the twins were discordant for schizophrenia and seven pairs in which both twins were normal) were counted by two persons trained in anthropometric research. Intrapair differences in the counts were then measured, and the differences among the pairs of normal twins were compared with the differences among the pairs discordant for schizophrenia. Results: The twins discordant for schizophrenia bad significantly greater absolute intrapair differences in total finger ridge count and significantly greater percent intrapair differences than the normal twins; i.e., their fingerprints were significantly less "twin-like." Conclusions: The study suggests that various second-trimester prenatal disturbances in the epigenesis of one twin in a pair discordant for schizophrenia may be related to the fact that only one of the twins expresses his or her genetic predisposition toward schizophrenia. This is consistent with a "two-strike" etiology of schizophrenia: a genetic diathesis plus a second-trimester environmental stressor. C1 UNIV ARKANSAS MED SCI HOSP,DEPT PSYCHIAT & BEHAV SCI,DIV CHILD & ADOLESCENT,LITTLE ROCK,AR 72205. ARKANSAS CHILDRENS HOSP,LITTLE ROCK,AR 72202. NIMH,TWIN STUDIES UNIT,WASHINGTON,DC 20032. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. RP BRACHA, HS (reprint author), VET AFFAIRS MED CTR,PSYCHIAT SERV,DEV NEUROPSYCHIAT RES UNIT,116-A1-NLR,N LITTLE ROCK,AR 72114, USA. RI G, I/D-8042-2011 FU NIMH NIH HHS [MH-41176, MH-43537] NR 43 TC 106 Z9 106 U1 0 U2 2 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 OCT PY 1992 VL 149 IS 10 BP 1355 EP 1361 PG 7 WC Psychiatry SC Psychiatry GA JP881 UT WOS:A1992JP88100009 PM 1530072 ER PT J AU MALLOY, MH HOFFMAN, HJ PETERSON, DR AF MALLOY, MH HOFFMAN, HJ PETERSON, DR TI SUDDEN-INFANT-DEATH-SYNDROME AND MATERNAL SMOKING SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CIGARETTE-SMOKING AB Data from Missouri for the period 1980 to 1985 suggest a dose-response relationship between smoking during pregnancy and the incidence of sudden infant death syndrome (SIDS). However, data from the National Institute of Child Health and Human Development SIDS Cooperative Epidemiological Study did not support a dose-response relationship. Neither the Missouri data nor the Cooperative Study data support a relationship between the age of occurrence of SIDS and smoking during pregnancy. C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. RP MALLOY, MH (reprint author), UNIV TEXAS,MED BRANCH,DEPT PEDIAT,RTE E-26,GALVESTON,TX 77550, USA. NR 8 TC 35 Z9 35 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 OCT PY 1992 VL 82 IS 10 BP 1380 EP 1382 DI 10.2105/AJPH.82.10.1380 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JQ399 UT WOS:A1992JQ39900015 PM 1415865 ER PT J AU WELLS, BL HORM, JW AF WELLS, BL HORM, JW TI STAGE AT DIAGNOSIS IN BREAST-CANCER - RACE AND SOCIOECONOMIC-FACTORS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ETHNIC-GROUPS; WOMEN; BLACK; MAMMOGRAPHY; SURVIVAL AB Cancer incidence data from three US metropolitan areas were coupled with census tract indicators of education and income. The data suggest that both Black and White cancer patients living in census tracts with lower median education/income values are diagnosed in later disease stages than are patients in tracts with higher median education/income values. Within education income strata, Black women had a less favorable stage of disease at diagnosis than Whites. The exception was in upper education/income levels, where the disadvantage for Blacks disappeared. These data provide additional evidence that women of low socioeconomic status could benefit from targeted screening. C1 NATL CTR HLTH STAT,DIV HLTH INTERVIEW STAT,HYATTSVILLE,MD 20782. RP WELLS, BL (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EPN-344,BETHESDA,MD 20892, USA. NR 22 TC 135 Z9 135 U1 2 U2 3 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 OCT PY 1992 VL 82 IS 10 BP 1383 EP 1385 DI 10.2105/AJPH.82.10.1383 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JQ399 UT WOS:A1992JQ39900016 PM 1415866 ER PT J AU LOCKSHIN, MD AF LOCKSHIN, MD TI OVERVIEW OF LUPUS PREGNANCIES SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT INTERNATIONAL CONF ON RHEUMATIC DISEASES IN PREGNANCY CY MAY 17-22, 1992 CL JERUSALEM, ISRAEL SP EUROPEAN LEAGUE AGANIST RHEUMATISM, INT LEAGUE AGAINST RHEUMATISM, ISREAL SOC RHEUMATOL, ISREAL SOC OBST & GYNECOL, NIAMS, TEL AVIV UNIV, MED SCH DE LUPUS; ANTIPHOSPHOLIPID ANTIBODY; NEONATAL LUPUS; LUPUS FLARE ID ANTIPHOSPHOLIPID ANTIBODY; HEART-BLOCK; ERYTHEMATOSUS; PATTERN; WOMEN; MODEL AB Pregnancy in patients with systemic lupus erythematosus (SLE) requires consideration of 5 major issues: (1) What is the risk to the mother? (2) What is the risk to the fetus? (3) What is the effect and treatment of antiphospholipid antibody? (4) What is the risk of neonatal lupus? (5) Stability of the family unit, particularly in the events of maternal disability or death, should be discussed by all parties when a pregnancy is planned. Consistency of measurement criteria, standardized treatment protocols, and long-term follow-ups are needed in the future. RP LOCKSHIN, MD (reprint author), NIAID,EXTRAMURAL PROGRAM,BLDG 31,ROOM 4C-32,BETHESDA,MD 20892, USA. NR 18 TC 8 Z9 10 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD OCT-DEC PY 1992 VL 28 IS 3-4 BP 181 EP 182 PG 2 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA KH728 UT WOS:A1992KH72800017 PM 1285874 ER PT J AU GRUBERG, L AKSENTIJEVICH, I PRAS, E KASTNER, DL PRAS, M AF GRUBERG, L AKSENTIJEVICH, I PRAS, E KASTNER, DL PRAS, M TI MAPPING OF THE FAMILIAL MEDITERRANEAN FEVER GENE TO CHROMOSOME-16 SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT INTERNATIONAL CONF ON RHEUMATIC DISEASES IN PREGNANCY CY MAY 17-22, 1992 CL JERUSALEM, ISRAEL SP EUROPEAN LEAGUE AGANIST RHEUMATISM, INT LEAGUE AGAINST RHEUMATISM, ISREAL SOC RHEUMATOL, ISREAL SOC OBST & GYNECOL, NIAMS, TEL AVIV UNIV, MED SCH DE FAMILIAL MEDITERRANEAN FEVER; GENE; CHROMOSOME ID AMYLOIDOSIS; COLCHICINE; ARMENIANS; FREQUENCY AB Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of fever, synovitis, peritonitis, or pleurisy. Some patients eventually develop systemic amyloidosis. The biochemical cause of the disease is unknown. We have conducted a genome-wide search for the FMF locus using 125 different DNA markers and mapped the FMF gene to the short arm of chromosome 16. The study was performed on 35 Israeli families primarily of North African and Iraqi origin. For the five markers D16S82 (p41-1 Sacl), D16S80 (24-1 Taql), D16S84 (pCMM65 Taql), D16S83 (pEKMDA2-1 Rsal), and HBA (5'HVR Rsal) we obtained maximum lod scores of 2.72 (theta = 0.08), 10.34 (theta = 0.04), 9.66 (theta = 0.050, 9.35 (theta = 0.03), and 14.31 (theta = 0.08), respectively. Multipoint analysis with HBA and D16S84 defined as a fixed loci gave a maximum lod score of 19.86 centromeric to D16S84. Crossovers defined by these markers place the FMF gene in an area of approximately 5 cM between D16S80 and D16S84. Other genes mapped to this area (16p13.3) include phosphodiesterase IB (PDE1B), hydroxyacyl-glutathione hydrolase (HAGH), phosphoglycolate phosphatase (PGP), and the gene that causes adult polycystic kidney disease (PKD1). None of these genes bear an obvious pathophysiological relationship to FMF. Using additional markers from this region we hope to localize more precisely the FMF gene and to offer the possibility of prenatal diagnosis in selected cases. Our ultimate goal is to isolate and characterize the FMF gene. C1 NIAID,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,DEPT MED F,IL-52621 TEL HASHOMER,ISRAEL. NIAID,HELLER INST MED RES,BETHESDA,MD 20892. NR 14 TC 12 Z9 12 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD OCT-DEC PY 1992 VL 28 IS 3-4 BP 241 EP 242 PG 2 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA KH728 UT WOS:A1992KH72800034 PM 1285890 ER PT J AU CABILI, S LIVNEH, A ZEMER, D RABINOVITCH, O PRAS, M AF CABILI, S LIVNEH, A ZEMER, D RABINOVITCH, O PRAS, M TI THE EFFECT OF PREGNANCY ON RENAL-FUNCTION IN AMYLOIDOSIS OF FAMILIAL MEDITERRANEAN FEVER SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT INTERNATIONAL CONF ON RHEUMATIC DISEASES IN PREGNANCY CY MAY 17-22, 1992 CL JERUSALEM, ISRAEL SP EUROPEAN LEAGUE AGANIST RHEUMATISM, INT LEAGUE AGAINST RHEUMATISM, ISREAL SOC RHEUMATOL, ISREAL SOC OBST & GYNECOL, NIAMS, TEL AVIV UNIV, MED SCH DE AMYLOIDOSIS; FAMILIAL MEDITERRANEAN FEVER; KIDNEY; PREGNANCY ID COLCHICINE AB The effect of pregnancy on kidney function was studied in 29 pregnancies of 17 patients with familial Mediterranean fever (FMF) and amyloidosis. Pregnancy associated deterioration of renal function occurred in seven patients who had advanced renal disease at conception, marked by serum creatinine greater-than-or-equal-to 1.5 mg/dl or urine protein greater-than-or-equal-to 2 g/24 h. This finding suggests that the severity of renal disease at conception may predict the fate of kidney function during pregnancy and puerperium. C1 NIAID,HELLER INST MED RES,BETHESDA,MD 20892. NIAID,DEPT MED,BETHESDA,MD 20892. NIAID,DEPT GYNECOL,BETHESDA,MD 20892. NR 4 TC 8 Z9 8 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD OCT-DEC PY 1992 VL 28 IS 3-4 BP 243 EP 244 PG 2 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA KH728 UT WOS:A1992KH72800035 PM 1285891 ER PT J AU GERGEN, PJ WEISS, KB AF GERGEN, PJ WEISS, KB TI THE INCREASING PROBLEM OF ASTHMA IN THE UNITED-STATES SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Editorial Material ID LUNG-FUNCTION; HOSPITALIZATION; CHILDREN; TRENDS; PREVALENCE; CHILDHOOD C1 GEORGE WASHINGTON UNIV,DEPT HLTH CARE SCI & MED,WASHINGTON,DC 20052. RP GERGEN, PJ (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,OFF EPIDEMIOL & CLIN TRIALS,BETHESDA,MD 20892, USA. NR 14 TC 91 Z9 91 U1 0 U2 1 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 OCT PY 1992 VL 146 IS 4 BP 823 EP 824 PG 2 WC Respiratory System SC Respiratory System GA JR471 UT WOS:A1992JR47100002 PM 1416404 ER PT J AU LEVINE, SJ KENNEDY, D SHELHAMER, JH KOVACS, A FEUERSTEIN, IM GILL, VJ STOCK, F SOLOMON, D BOYLEN, CT MASUR, H OGNIBENE, FP AF LEVINE, SJ KENNEDY, D SHELHAMER, JH KOVACS, A FEUERSTEIN, IM GILL, VJ STOCK, F SOLOMON, D BOYLEN, CT MASUR, H OGNIBENE, FP TI DIAGNOSIS OF PNEUMOCYSTIS-CARINII PNEUMONIA BY MULTIPLE LOBE, SITE-DIRECTED BRONCHOALVEOLAR LAVAGE WITH IMMUNOFLUORESCENT MONOCLONAL-ANTIBODY STAINING IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS RECEIVING AEROSOLIZED PENTAMIDINE CHEMOPROPHYLAXIS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; TRANS-BRONCHIAL BIOPSY; INDUCED SPUTUM; AIDS; COMPLICATIONS; PROPHYLAXIS; SPECIMENS; LUNG AB The yields of both induced sputum examination and bronchoalveolar lavage (BAL) have been reported to be decreased for breakthrough episodes of Pneumocystis carinii pneumonia in human immunodeficiency virus-Infected patients receiving aerosolized pentamidine chemoprophylaxis. This study assessed whether the yield of a single middle or lower lobe BAL could be Increased by the utilization of two techniques. (1) Indirect immunofluorescent staining with a combination of two murine monoclonal anti-Pneumocystis antibodies in addition to routine toluidine blue O and cytopathologic staining, and (2) the performance of multiple lobe, site-directed BAL (i.e., both upper lobe and middle or lower lobe lavage, including the lobe with the greatest radiographic abnormality). Results of 252 fiberoptic bronchoscopies performed at the National Institutes of Health and the Los Angeles County-University of Southern California Medical Center were analyzed. P carinii pneumonia was documented in 21 episodes in patients who did not receive prior anti-Pneumocystis chemoprophylaxis and in 41 episodes in patients who received aerosolized pentamidine. Monoclonal antibody staining and multiple lobs, site-directed BAL resulted in similar diagnostic yields for p. carinii in the nonprophylaxis (100%) and aerosolized pentamidine (98%) groups. If BAL had been performed without monoclonal antibody staining and multiple lobe, site-directed lavage, then the yield would have decreased to 95% in the nonprophylaxis group and to 80% in the aerosolized pentamidine group. When the yields for single middle or lower lobe BAL without monoclonal antibody staining and multiple lobe, site-directed BAL with monoclonal antibody staining were compared in patients receiving aerosolized pentamidine, the sensitivity was significantly improved when both supplemental techniques were used (98% versus 80%, p < 0.03, Fisher's exact test). These data suggest that the use of both immunofluorescent monoclonal antibody staining and multiple lobe, site-directed BAL, in addition to middle or lower lobe lavage and conventional staining techniques, can maintain the high positive yield of BAL for R carinii in patients receiving aerosolized pentamidine chemoprophylaxis. C1 NCI,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NCI,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV SO CALIF,LOS ANGELES CTY MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90033. UNIV SO CALIF,LOS ANGELES CTY MED CTR,DIV PULM & CRIT CARE MED,LOS ANGELES,CA 90033. NR 32 TC 40 Z9 40 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD OCT PY 1992 VL 146 IS 4 BP 838 EP 843 PG 6 WC Respiratory System SC Respiratory System GA JR471 UT WOS:A1992JR47100005 PM 1416407 ER PT J AU MEINI, S EVANGELISTA, S GEPPETTI, P SZALLASI, A BLUMBERG, PM MANZINI, S AF MEINI, S EVANGELISTA, S GEPPETTI, P SZALLASI, A BLUMBERG, PM MANZINI, S TI PHARMACOLOGICAL AND NEUROCHEMICAL EVIDENCE FOR THE ACTIVATION OF CAPSAICIN-SENSITIVE SENSORY NERVES BY LIPOXIN-A4 IN GUINEA-PIG BRONCHUS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID ARACHIDONIC-ACID; SUBSTANCE-P; AIRWAY EPITHELIUM; HUMAN-LEUKOCYTES; SMOOTH-MUSCLE; RELEASE; INVOLVEMENT; LEUKOTRIENE-D4; ASTHMA; HYPERRESPONSIVENESS AB Exogenous administration of lipoxin A4 (LXA4) to guinea pig isolated bronchus produced contractile effects in a concentration-dependent manner (1, 3, and 6 muM). These responses were Potentiated when preparations were previously incubated with thiorphan (10 muM), an inhibitor of tachykinin breakdown, but were significantly depressed when sensory nerves were previously desensitized in vitro by capsaicin (10 muM for 15 min) challenge. Ruthenium red (10 muM for 20 min), a blocker of the cationic channel coupled to the capsaicin receptor, also produced, although in a weaker manner, a reduction in bronchomotor responses elicited by LXA4. On the other hand, preexposure to omega-conotoxin (0.1 muM for 45 min), a blocker of neuronal voltage-dependent Ca2+ channels, did not modify the LXA4 contractile effects. Furthermore, LXA4 (6 muM) superfusion of guinea pig bronchial tissue elicited a significant calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) release that was reduced by capsaicin (10 muM, 30 min) desensitization. Finally, LXA4 (10 muM) was unable to displace [H-3]resiniferatoxin binding in dorsal root ganglion of rat and guinea pig. These findings support (1) a role for LXA4 in activating motor sensory function of capsaicin-sensitive nerves; (2) this activation mechanism is marginally ruthenium red-sensitive and omega-conotoxin-residant; and (3) the interaction does not involve the recognized binding site on the vanilloid receptor. As a whole this study presents LXA4 as an endogenous mediator activating sensory nerves potentially involved in basic mechanisms of airway diseases. C1 MALESCI SPA,IST FARMACOBIOL,RES LABS,DEPT PHARMACOL,FLORENCE,ITALY. UNIV FLORENCE,DEPT INTERNAL MED,I-50121 FLORENCE,ITALY. NIH,CELLULAR CARCINOGENESIS & TUMOUR PROMOT LAB,BETHESDA,MD 20892. MENARINI SUD,RES LABS,DEPT PHARMACOL,ROME,ITALY. NR 44 TC 22 Z9 22 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD OCT PY 1992 VL 146 IS 4 BP 930 EP 934 PG 5 WC Respiratory System SC Respiratory System GA JR471 UT WOS:A1992JR47100021 PM 1384407 ER PT J AU GOPALAKRISHNA, R CHEN, ZH GUNDIMEDA, U WILSON, JC ANDERSON, WB AF GOPALAKRISHNA, R CHEN, ZH GUNDIMEDA, U WILSON, JC ANDERSON, WB TI RAPID FILTRATION ASSAYS FOR PROTEIN-KINASE-C ACTIVITY AND PHORBOL ESTER BINDING USING MULTIWELL PLATES WITH FITTED FILTRATION DISKS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID MEMBRANE ASSOCIATION; DISTINCT FORMS; BRAIN CYTOSOL; RAT-BRAIN; ACTIVATION; CALCIUM; CELLS; IDENTIFICATION; HETEROGENEITY; INCREASE C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. RP GOPALAKRISHNA, R (reprint author), UNIV SO CALIF,SCH MED,DEPT PHARMACOL & NUTR,LOS ANGELES,CA 90033, USA. FU NCI NIH HHS [CA 47142] NR 34 TC 45 Z9 45 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT PY 1992 VL 206 IS 1 BP 24 EP 35 DI 10.1016/S0003-2697(05)80006-5 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JR731 UT WOS:A1992JR73100005 PM 1456438 ER PT J AU IWAHASHI, H PARKER, CE MASON, RP TOMER, KB AF IWAHASHI, H PARKER, CE MASON, RP TOMER, KB TI COMBINED LIQUID-CHROMATOGRAPHY ELECTRON-PARAMAGNETIC RESONANCE SPECTROMETRY ELECTROSPRAY IONIZATION MASS-SPECTROMETRY FOR RADICAL IDENTIFICATION SO ANALYTICAL CHEMISTRY LA English DT Article ID SPIN-TRAPPED RADICALS; TERT-BUTYL NITRONE; GC MS; ADDUCTS; METABOLISM; ACID; SPECTROSCOPY; SEPARATION; HYDROXYL; PBN AB Electron paramagnetic resonance (EPR) spectrometry and mass spectrometry (MS) have been coupled together on-line with liquid chromatography (LC)/UV detection. These combined techniques have been applied to the determination of spin-trapped radical adducts, including phenyl, 2-, 3-, and 4- chlorophenyl, and 2-bromophenyl radicals trapped with alpha-(1-oxo-4-pyridyl)-N-tert-butyinitrone (4-POBN), and phenyl radicals trapped with 2-methyl-2-nitrosopropane (MNP), alpha-phenyl-N-tert-butyinitrone (PBN), and 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Oxidized and reduced forms of the radical adducts were also detected by the on-line LC/EPR/Ms system. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 34 TC 52 Z9 54 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD OCT 1 PY 1992 VL 64 IS 19 BP 2244 EP 2252 DI 10.1021/ac00043a011 PG 9 WC Chemistry, Analytical SC Chemistry GA JQ527 UT WOS:A1992JQ52700012 PM 1333174 ER PT J AU TOMASEK, JJ AKIYAMA, SK AF TOMASEK, JJ AKIYAMA, SK TI FIBROBLAST-MEDIATED COLLAGEN GEL CONTRACTION DOES NOT REQUIRE FIBRONECTIN-ALPHA-5-BETA-1 INTEGRIN INTERACTION SO ANATOMICAL RECORD LA English DT Article DE EXTRACELLULAR MATRIX; WOUND HEALING; MORPHOGENESIS ID EXTRACELLULAR-MATRIX RECEPTORS; CELL-ADHESION; FIBRONECTIN RECEPTOR; MONOCLONAL-ANTIBODIES; PLASMA FIBRONECTIN; IDENTIFICATION; BINDING; PROTEIN; FAMILY; REORGANIZATION AB Fibroblasts cultured within free-floating collagen gels can bind to and reorganize the surrounding collagen fibrils into a more dense and compact arrangement. Collagen gel contraction provides an in vitro model for studying fibroblast-collagen interactions important in wound healing, fibrosis, scar contraction, and connective tissue morphogenesis. We have assessed the role of fibronectin and its interaction with the alpha-5-beta-1 "high affinity" fibronectin-specific integrin receptor in collagen gel contraction. A variety of agents, which specifically inhibit fibronectin-alpha-5-beta-1, interactions, were tested for their abilities to inhibit fibroblast-mediated collagen gel contraction. These included anti-alpha-5-beta-1 monoclonal antibodies, the synthetic peptide GRGDSP, the cell adhesive fragment of fibronectin, and an antibody against the cell adhesive region of fibronectin. None of these agents inhibited collagen gel contraction. Therefore, it is concluded that fibronectin-alpha-5-beta-1 interactions are not necessary for collagen gel contraction. However, collagen gel contraction is dependent on a member or members of the beta-1 subfamily of integrin matrix receptors. A polyclonal antiserum and a monoclonal antibody, both directed against the beta-1 subunit of integrin matrix receptors, inhibited the spreading of fibroblasts in the collagen gel and inhibited collagen gel contraction. This study demonstrates that fibroblast-mediated collagen gel contraction is independent of fibronectin-alpha-5-beta-1 interactions but dependent on an interaction of beta-1 integrin matrix receptors with collagen fibers. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP TOMASEK, JJ (reprint author), UNIV OKLAHOMA,HLTH SCI CTR,DEPT ANAT SCI,BIOMED SCI BLDG,RM 553,POB 26901,OKLAHOMA CITY,OK 73190, USA. NR 37 TC 33 Z9 33 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 0003-276X J9 ANAT REC JI Anat. Rec. PD OCT PY 1992 VL 234 IS 2 BP 153 EP 160 DI 10.1002/ar.1092340202 PG 8 WC Anatomy & Morphology SC Anatomy & Morphology GA JN132 UT WOS:A1992JN13200001 PM 1416102 ER PT J AU UNSICKER, K ENGELS, S HAMM, C LUDECKE, G MEIER, C RENZING, J TERBRACK, HG FLANDERS, K AF UNSICKER, K ENGELS, S HAMM, C LUDECKE, G MEIER, C RENZING, J TERBRACK, HG FLANDERS, K TI MOLECULAR CONTROL OF NEURAL PLASTICITY BY THE MULTIFUNCTIONAL GROWTH-FACTOR FAMILIES OF THE FGFS AND TGF-BETA-S SO ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER LA English DT Article; Proceedings Paper CT 87TH ASSEMBLY OF THE ANATOMICAL SOC CY MAR 23-26, 1992 CL MAINZ, GERMANY SP ANATOM SOC ID NERVOUS-SYSTEM; SEPTAL NEURONS; SURVIVAL; NGF C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP UNSICKER, K (reprint author), UNIV MARBURG,DEPT ANAT & CELL BIOL,ROBERT KOCH STR 6,W-3550 MARBURG,GERMANY. NR 18 TC 12 Z9 12 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0940-9602 J9 ANN ANAT JI Ann. Anat.-Anat. Anz. PD OCT PY 1992 VL 174 IS 5 BP 405 EP 407 PG 3 WC Anatomy & Morphology SC Anatomy & Morphology GA JV388 UT WOS:A1992JV38800006 PM 1449217 ER PT J AU NELSON, KE DONAHUE, JG MUNOZ, A COHEN, ND NESS, PM TEAGUE, A STAMBOLIS, VA YAWN, DH CALLICOTT, B MCALLISTER, H REITZ, BA LEE, H FARZADEGAN, H HOLLINGSWORTH, CG AF NELSON, KE DONAHUE, JG MUNOZ, A COHEN, ND NESS, PM TEAGUE, A STAMBOLIS, VA YAWN, DH CALLICOTT, B MCALLISTER, H REITZ, BA LEE, H FARZADEGAN, H HOLLINGSWORTH, CG TI TRANSMISSION OF RETROVIRUSES FROM SERONEGATIVE DONORS BY TRANSFUSION DURING CARDIAC-SURGERY - A MULTICENTER STUDY OF HIV-1 AND HTLV-I/II INFECTIONS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE HTLV-I; HTLV-II; BLOOD TRANSFUSION; HUMAN IMMUNODEFICIENCY VIRUS; ACQUIRED IMMUNODEFICIENCY SYNDROME ID IMMUNODEFICIENCY-VIRUS TYPE-1; LYMPHOTROPIC VIRUS; HOMOSEXUAL MEN; BLOOD-DONORS; ACQUIRED IMMUNODEFICIENCY; SCREENED BLOOD; NEGATIVE BLOOD; DRUG-ABUSERS; I INFECTION; ANTIBODY AB Objective: To evaluate the effectiveness of serologic testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types I and II (HTLV-I/II) infections and to estimate the risk for transmission of HIV-1 and HTLV-I/II by transfusion of seronegative blood from screened donors. Design: A prospective multicenter cohort study of cardiac surgery patients who received multiple transfusions between 1985 and 1991. Setting: Cardiac surgery services of three large tertiary care hospitals. Patients: The study included 11 532 patients in three hospitals who had cardiovascular surgery. Measurements: Incident HIV-1 and HTLV-I or HTLV-II infection. Results: We detected two new HIV-1 infections among patients transfused with 120 312 units of blood components from seronegative donors. In each case a donor was detected on follow-up who had seroconverted since the donation. The HIV-1 infection rate was 0.0017% with an upper limit of the 95% Cl of 0.0053%. Before donor screening for HTLV-I, transfusion of 51 026 units resulted in two HTLV-I infections (0.0039%) and four HTLV-II infections (0.0078%). After HTLV-I screening was instituted, one recipient was infected with HTLV-II among participants exposed to 69 272 units, a rate of 0.0014%. A corresponding HTLV-I/II-infected donor was found for this patient. Conclusion: Serologic screening of donors for antibodies to HIV-1 and HTLV-I coupled with exclusion of donors from groups having a relatively high risk for infection has led to a low incidence of transfusion-transmitted HIV-1 and HTLV-I/II infection in the United States. A small risk remains, however, despite these measures. We estimate the residual risk for HIV-1 and HTLV-II infection from transfusion of screened blood during the time of this study to be about 1 in 60 000 units. C1 JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. ST LUKES EPISCOPAL HOSP,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON,TX 77030. METHODIST HOSP,HOUSTON,TX 77030. ABBOTT LABS,N CHICAGO,IL. NHLBI,BETHESDA,MD 20892. RP NELSON, KE (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,624 N BROADWAY,ROOM 886,BALTIMORE,MD 21205, USA. OI Cohen, Noah/0000-0002-0384-2903 FU NCRR NIH HHS [5M01RR00722]; NHLBI NIH HHS [1-HB-6-7025] NR 35 TC 71 Z9 73 U1 0 U2 1 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 OCT 1 PY 1992 VL 117 IS 7 BP 554 EP 559 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JQ226 UT WOS:A1992JQ22600002 PM 1524329 ER PT J AU LAGAKOS, S HOTH, DF AF LAGAKOS, S HOTH, DF TI SURROGATE MARKERS IN AIDS - IN RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NIH,BETHESDA,MD 20892. RP LAGAKOS, S (reprint author), HARVARD UNIV,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 1992 VL 117 IS 7 BP 619 EP 619 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JQ226 UT WOS:A1992JQ22600024 ER PT J AU HOFFMAN, GS FAUCI, AS AF HOFFMAN, GS FAUCI, AS TI WEGENER GRANULOMATOSIS - IN RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP HOFFMAN, GS (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 1992 VL 117 IS 7 BP 620 EP 621 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JQ226 UT WOS:A1992JQ22600029 ER PT J AU CHANAUD, CM LUDLOW, CL AF CHANAUD, CM LUDLOW, CL TI SINGLE MOTOR UNIT-ACTIVITY OF HUMAN INTRINSIC LARYNGEAL MUSCLES DURING RESPIRATION SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE FIRING PATTERNS; INTRINSIC LARYNGEAL MUSCLES; LARYNGEAL MOTONEURONS; MOTOR UNIT ACTIVITY; RESPIRATION ID VOLUNTARY ISOMETRIC CONTRACTIONS; POSTERIOR CRICOARYTENOID MUSCLE; HISTOCHEMICAL-CHARACTERISTICS; CRICOTHYROID MUSCLE; LOCOMOTION; SLEEP; CORD AB Individual motor units in the thyroarytenoid (TA) and cricothyroid (CT) muscles were studied in 10 normal human volunteers during quiet respiration. Both tonic and phasic firing patterns were found in both TA and CT units. The rate of firing was higher during inhalation than during exhalation in phasic TA units and in tonic CT units. Tonically active units had a higher firing frequency than phasically active units in both TA and CT muscles. Phasically active units corresponded with the respiratory cycle, with firing associated with inhalation in both the TA and CT muscles. A variety of firing patterns were found between units in both the TA and CT muscles, and in one subject, units recorded from the same muscle had very different firing patterns. The results suggest that although laryngeal motoneurons are modulated by the respiratory cycle, they do not respond uniformly to respiration. C1 NIDCD,VOICE & SPEECH SECT,BLDG 10,ROOM 5D38,BETHESDA,MD 20892. OI Ludlow, Christy/0000-0002-2015-6171 NR 28 TC 25 Z9 25 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 1992 VL 101 IS 10 BP 832 EP 840 PN 1 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA JU235 UT WOS:A1992JU23500006 PM 1416638 ER PT J AU MITCHELL, ME DEBOER, DA CRITTENDEN, MD CLARK, RE AF MITCHELL, ME DEBOER, DA CRITTENDEN, MD CLARK, RE TI NICARDIPINE - MYOCARDIAL PROTECTION IN ISOLATED WORKING HEARTS SO ANNALS OF THORACIC SURGERY LA English DT Article ID CALCIUM-ANTAGONISTS; ISCHEMIC INJURY; NIFEDIPINE; CARDIOPLEGIA; VERAPAMIL; ACCUMULATION; PRESERVATION; EXPERIENCE; DILTIAZEM; CA2+ AB The effectiveness of the calcium antagonist nicardipine in protecting the ischemic myocardium was evaluated using the hemodynamic recovery of isolated working rat hearts subjected to hyperkalemic cardiac arrest followed by ischemia at 37.5-degrees-C and 10-degrees-C. Rat hearts (n = 51) received 20 mL of cardioplegia and were subjected to 27 minutes of ischemia at 37.5-degrees-C. Group A (control) did not receive nicardipine. Groups B through F received nicardipine in the cardioplegia with total doses ranging from 2 mug to 6 mug. Group A had 46% survival of ischemia, whereas groups C (3 mug) and D (4 mug) had survival rates of 88% and 100%, respectively (p < 0.05). The recovery of aortic flow after ischemia was 35% in group A, compared with 76% in group B (2 mug) and 81% in group D (p < 0.05). Group A had 49% postischemic recovery of cardiac output, whereas groups B and D had 82% and 85% recovery (p < 0.05). The postischemic recovery of stroke volume was 48% in group A compared with 84% in group B, 87% in group D, and 73% in group E (5 mug) (p < 0.05). Additional rats were exposed to 210 minutes of ischemia (n = 41) or 240 minutes of ischemia (n = 56) at 10-degrees-C. Control groups did not receive nicardipine, whereas treatment groups received nicardipine in the cardioplegia with total doses ranging from 1.4 mug to 6.4 mug. There were no significant differences in the survival of ischemia or the recovery of function after ischemia at 10-degrees-C. We conclude that nicardipine offers significant protection to the ischemic rat myocardium at normothermia, with an optimal dose of 2 to 4 mug. We have been unable to demonstrate any beneficial effect from the administration of nicardipine at 10-degrees-C. C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. NR 25 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 1992 VL 54 IS 4 BP 712 EP 716 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA JP898 UT WOS:A1992JP89800015 PM 1417229 ER PT J AU PAI, LH SWAIN, SM VENZON, DJ REED, E POIRIER, MC GUPTABURT, S DENICOFF, AM ALLEGRA, CJ AF PAI, LH SWAIN, SM VENZON, DJ REED, E POIRIER, MC GUPTABURT, S DENICOFF, AM ALLEGRA, CJ TI THERAPY OF PATIENTS WITH METASTATIC BREAST-CANCER WITH 5-FLUOROURACIL, LEUCOVORIN AND CARBOPLATIN SO ANTI-CANCER DRUGS LA English DT Article DE ADVANCED BREAST CANCER; CARBOPLATIN; DNA ADDICT; 5-FLUOROURACIL; LEUCOVORIN ID HIGH-DOSE LEUCOVORIN; ADVANCED COLORECTAL-CARCINOMA; LOCALLY ADVANCED HEAD; DNA ADDUCT LEVELS; FOLINIC ACID; BIOCHEMICAL MODULATION; 5-FU INFUSION; NECK-CANCER; PHASE-II; CISPLATIN AB Thirty-four women with metastatic breast cancer were treated at the National Cancer Institute of the National Institutes of Health, with a regimen of leucovorin (L), 500 mg/m2 i.v. over 30 min, followed in 1 h by 5-fluorouracil (5-FU), 375 mg/m2 i.v. bolus on days 1-5, and carboplatin (CBDCA), 50-100 mg/m2 i.v. bolus on days 2-4, every 28 days. All patients had received previous combination chemotherapy with at least one regimen (29 patients with 5-FU-containing regimens). CBDCA, 100 mg/m2 on days 2-4, resulted in grade 4 neutropenia in 10 out of 11 patients associated with sepsis in all 10 patients. CBDCA, 75 mg/m2 (seven patients) and 50 mg/m2 (15 patients), resulted in grade 4 neutropenia in six and eight patients, and neutropenic sepsis in five and two cases, respectively. Grade 4 thrombocytopenia occurred in 10, five and two patients receiving 100, 75 and 50 mg/m2 of CBDCA, respectively. Other toxicities included grade 3/4 mucositis in 18 patients and grade 3/4 diarrhea in 10 patients. Twenty nine patients were evaluable for response, with one pathologic complete response (3%), two partial responses (6%), 18 stable disease (53%) and eight (24%) progressive disease. Sites of response included bone, viscera and soft tissue. The median time from entry on study to progression, for responders, was 15 months. When platinum-DNA adduct formation in peripheral white blood cells was analyzed in 27 patients at 24 h after drug administration, a significant correlation between adduct level and CBDCA cumulative dose was found. However, no statistically significant correlation was found between platinum-DNA adduct formation and disease response, survival or toxicity in this study. The results presented here suggest that the combination of 5-FU, L and CBDCA is tolerable at a CBDCA dose of 50 mg/m2 days 2-4; however, higher doses of CBDCA are poorly tolerated due to hematologic toxicity. At the CBDCA dose level of 50 mg/m2 on days 2-4, no significant disease responses were observed. We conclude that higher doses of CBDCA are highly toxic and limited our ability to deliver adequate doses of L-modulated 5-FU. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NCI,DIV CANC EPIDEMIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 31 TC 4 Z9 4 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD OCT PY 1992 VL 3 IS 5 BP 463 EP 469 DI 10.1097/00001813-199210000-00003 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA JU232 UT WOS:A1992JU23200003 PM 1450439 ER PT J AU MORGAN, ME CHI, SC MURAKAMI, K MITSUYA, H ANDERSON, BD AF MORGAN, ME CHI, SC MURAKAMI, K MITSUYA, H ANDERSON, BD TI CENTRAL-NERVOUS-SYSTEM TARGETING OF 2',3'-DIDEOXYINOSINE VIA ADENOSINE DEAMINASE-ACTIVATED 6-HALO-DIDEOXYPURINE PRODRUGS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; CEREBROSPINAL-FLUID; INTRAVENOUS-INFUSION; UPTAKE KINETICS; ZIDOVUDINE AZT; BRAIN; NUCLEOSIDES; HIV; 3'-AZIDO-3'-DEOXYTHYMIDINE AB AIDS dementia complex is a neurologic disorder, characterized by increasingly severe cognitive, behavioral, and motor impairment, which is associated with human immunodeficiency virus (HIV) infection in the central nervous system (CNS). Many of the dideoxynucleosides effective systemically in the treatment of HIV infections, such as 2',3'-dideoxyinosine (ddI), exhibit limited penetration into the CNS and limited or variable effectiveness in reversing the symptoms of AIDS dementia. Thus, approaches for increasing the CNS uptake of ddI and other dideoxynucleosides are needed. The CNS uptake of a series of 6-halo-2',3'-dideoxypurine ribofuranosides (6-halo-ddPs) previously shown to be active against HIV because of their conversion to ddI through the action of adenosine deaminase was examined in rats. In vitro studies in rat blood and brain tissue homogenate suggested a favorable selectivity for bioconversion in brain tissue, but with bioconversion half-lives varying widely within the series. In vivo infusions of 6-chloro-ddP (6-Cl-ddP), 6-bromo-ddP (6-Br-ddP), and 6-iodo-ddP (6-I-ddP) resulted in significant increases (20- to 34-fold) in the ddI concentration ratios in brain parenchyma/plasma when compared with those after an infusion of ddI alone. Absolute concentrations of ddI in brain parenchyma were increased 10- and 4-fold, respectively, following 30-min infusions of 6-Cl-ddP or 6-Br-ddP, but were 2.4-fold lower after an infusion of 6-I-ddP relative to that after a control infusion of ddI. Detailed studies of the plasma pharmacokinetics, CNS uptake kinetics, and bioconversion of 6-Cl-ddP were conducted to compare in vivo transport and bioconversion parameters with those predicted from in vitro measurements and to rationalize the efficiency of CNS delivery of ddI from 6-Cl-ddP. The results show that increased lipophilicity alone does not ensure that a given prodrug will deliver higher levels of a parent compound to the CNS. Both the selectivity and absolute rate of bioconversion in the brain are important factors. C1 UNIV UTAH,DEPT PHARMACEUT,SALT LAKE CITY,UT 84112. SANYO KOKUSAKU PULP CO,IWAKUNI 740,JAPAN. NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. FU NIAID NIH HHS [N01 AI 82680] NR 43 TC 39 Z9 39 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1992 VL 36 IS 10 BP 2156 EP 2165 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA JQ679 UT WOS:A1992JQ67900014 PM 1444295 ER PT J AU BARTOSHUK, LM KARRER, TA KVETON, JF YANAGISAWA, K CATALANOTTO, FA LEHMAN, CD WEIFFENBACH, JM AF BARTOSHUK, LM KARRER, TA KVETON, JF YANAGISAWA, K CATALANOTTO, FA LEHMAN, CD WEIFFENBACH, JM TI ANESTHESIA OF THE FACIAL NERVE-(VII) ALTERS TASTE RESPONSES FROM THE GLOSSOPHARYNGEAL NERVE-(IX) AND PRODUCES TASTE PHANTOMS SO APPETITE LA English DT Meeting Abstract C1 YALE UNIV,SCH MED,DEPT SURG,NEW HAVEN,CT 06510. UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195. NIDR,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-6663 J9 APPETITE JI Appetite PD OCT PY 1992 VL 19 IS 2 BP 161 EP 161 DI 10.1016/0195-6663(92)90024-Z PG 1 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA JX156 UT WOS:A1992JX15600012 ER PT J AU KELLER, MB LAVORI, PW MUELLER, TI ENDICOTT, J CORYELL, W HIRSCHFELD, RMA SHEA, T AF KELLER, MB LAVORI, PW MUELLER, TI ENDICOTT, J CORYELL, W HIRSCHFELD, RMA SHEA, T TI TIME TO RECOVERY, CHRONICITY, AND LEVELS OF PSYCHOPATHOLOGY IN MAJOR DEPRESSION - A 5-YEAR PROSPECTIVE FOLLOW-UP OF 431 SUBJECTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID AFFECTIVE-DISORDER; EPISODES; PREDICTORS; REGRESSION; CRITERIA; RELAPSE; FAMILY AB The course of illness of 431 subjects with major depression participating in the National Institute of Mental Health Collaborative Depression Study was prospectively observed for 5 years. Twelve percent of the subjects still had not recovered by 5 years. There were decreasing rates of recovery over time. For example, 50% of the subjects recovered within the first 6 months, and then the rate of recovery declined markedly. Instantaneous probabilities of recovery reflect that the longer a patient was ill, the lower his or her chances were of recovering. For patients still depressed, the likelihood of recovery within the next month declined from 15% during the first 3 months of follow-up to 1% to 2% per month during years 3, 4, and 5 of this follow-up. The severity of current psychopathology predicted the probability of subsequent recovery. Subjects with moderately severe depressive symptoms, minor depression, or dysthymia had an 18-fold greater likelihood of beginning recovery within the next week than did subjects who were at full criteria for major depressive disorder. Many subjects who did not recover continued in an episode that looked more like dysthymia than major depressive disorder. C1 BROWN UNIV,NATL INST MENTAL HLTH COLLABORAT PROGRAM PSYCHOBIOL DEPRESS,PROVIDENCE,RI 02912. NEW YORK STATE PSYCHIAT INST & HOSP,DEPT RES & TRAINING,NEW YORK,NY 10032. UNIV IOWA,COLL MED,DEPT PSYCHIAT,IOWA CITY,IA 52242. UNIV TEXAS,MED BRANCH,DEPT PSYCHIAT & BEHAV SCI,GALVESTON,TX 77550. RP KELLER, MB (reprint author), BROWN UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02912, USA. FU NIMH NIH HHS [R01 MH025478] NR 38 TC 617 Z9 632 U1 1 U2 28 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 OCT PY 1992 VL 49 IS 10 BP 809 EP 816 PG 8 WC Psychiatry SC Psychiatry GA JR569 UT WOS:A1992JR56900010 PM 1417434 ER PT J AU STARK, WJ STULTING, RD BIAS, WB FINK, NE FOULKS, GN KURINIJ, N MAGUIRE, MG MEYER, RF RAPOZA, P SMITH, RE MAGUIRE, MG FINK, NE ENGER, CL KRASKA, EW JOHNSON, R SEAY, M KLEIN, PE HILLIS, AI YOUNG, EM BOISJOLY, HM BIAS, WB HOPKINS, KA HELMSEN, R THOFT, R DAVIS, CE GOEKEN, N STREILEIN, JW VEATCH, R AMES, J STRAWN, J MEYER, RF SUGAR, A SOONG, HK WALDO, MN POPE, C WIEDMAYER, L DRAKE, K BAKER, JR HAINES, R SCHALL, C LINDENAUER, MR DANNEFFEL, MB EAST, M WARING, GO ANTOVEL, DB SHAWSMITH, P GEMMILL, M STREET, D LINDERMAN, P WHITSETT, C BRAY, J ABERNATHY, YT GOTTSCH, JD TAYLOR, H SCHEIN, O KANE, LF PRATZER, K KAMP, M LIVINGSTON, A FENNEMAN, A FENTON, J WEBSTER, N NEISSER, L SEABROOK, S RITTER, J HOPKINS, KA MURPHY, P STERNER, KD TERLIZZESE, KC MADISON, B FOULKS, GN COBO, M JONES, SB SKALAK, C KELLY, A SANFILIPPO, F MACQUEEN, JM GREEN, B WILLIAMS, J WILLIAMS, W SMITH, RE IRVINE, J MCDONNELL, P SCHANZLIN, D ROBIN, J MILLERSCHOLTE, A CISNEROS, L GARBUS, J STEBER, M QUILLENTHOMAS, B TERASAKI, P CICCIARELLI, J YUGE, J WARD, D CROWL, B WINGATE, M RAPOZA, P CHANDLER, JW SHAPIRO, M SCHWARTZ, A PRESTIA, PA GROOS, J GAUSAS, C GOYINGS, N LUCEY, M HEIM, S SOLLINGER, HW LORENTZEN, DF KELM, MC LISITZA, MA AF STARK, WJ STULTING, RD BIAS, WB FINK, NE FOULKS, GN KURINIJ, N MAGUIRE, MG MEYER, RF RAPOZA, P SMITH, RE MAGUIRE, MG FINK, NE ENGER, CL KRASKA, EW JOHNSON, R SEAY, M KLEIN, PE HILLIS, AI YOUNG, EM BOISJOLY, HM BIAS, WB HOPKINS, KA HELMSEN, R THOFT, R DAVIS, CE GOEKEN, N STREILEIN, JW VEATCH, R AMES, J STRAWN, J MEYER, RF SUGAR, A SOONG, HK WALDO, MN POPE, C WIEDMAYER, L DRAKE, K BAKER, JR HAINES, R SCHALL, C LINDENAUER, MR DANNEFFEL, MB EAST, M WARING, GO ANTOVEL, DB SHAWSMITH, P GEMMILL, M STREET, D LINDERMAN, P WHITSETT, C BRAY, J ABERNATHY, YT GOTTSCH, JD TAYLOR, H SCHEIN, O KANE, LF PRATZER, K KAMP, M LIVINGSTON, A FENNEMAN, A FENTON, J WEBSTER, N NEISSER, L SEABROOK, S RITTER, J HOPKINS, KA MURPHY, P STERNER, KD TERLIZZESE, KC MADISON, B FOULKS, GN COBO, M JONES, SB SKALAK, C KELLY, A SANFILIPPO, F MACQUEEN, JM GREEN, B WILLIAMS, J WILLIAMS, W SMITH, RE IRVINE, J MCDONNELL, P SCHANZLIN, D ROBIN, J MILLERSCHOLTE, A CISNEROS, L GARBUS, J STEBER, M QUILLENTHOMAS, B TERASAKI, P CICCIARELLI, J YUGE, J WARD, D CROWL, B WINGATE, M RAPOZA, P CHANDLER, JW SHAPIRO, M SCHWARTZ, A PRESTIA, PA GROOS, J GAUSAS, C GOYINGS, N LUCEY, M HEIM, S SOLLINGER, HW LORENTZEN, DF KELM, MC LISITZA, MA TI THE COLLABORATIVE CORNEAL TRANSPLANTATION STUDIES (CCTS) - EFFECTIVENESS OF HISTOCOMPATIBILITY MATCHING IN HIGH-RISK CORNEAL TRANSPLANTATION SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID HLA ANTIGENS; PENETRATING KERATOPLASTY; CELLS; REJECTION; SURVIVAL AB The Collaborative Corneal Transplantation Studies (CCTS) were designed to evaluate the effect of donor-recipient histocompatibility matching and crossmatching on the survival of corneal transplants in high-risk patients. Corneas were allocated to the 419 patients in the double-masked Antigen Matching Study on the basis of serologically defined HLA-A, -B and HLA-DR antigen match. ABO blood group compatibility was determined but not used for recipient selection. The 37 patients in the Crossmatch Study were randomly assigned to receive a cornea from either a positively or negatively crossmatched donor. All patients received topical steroid therapy according to a standard protocol. Matching for HLA-A, -B and HLA-DR antigens had no effect on overall graft survival, the incidence of irreversible rejection, or the incidence of rejection episodes. At 3 years after surgery, the estimated proportion of eyes with graft failure was 41% for the ABO-incompatible group and 31% for the ABO-compatible group (relative risk, 1.43; 95% confidence interval, 1.00 to 2.06). The estimated proportion of eyes with failure from rejection by 3 years was 30% for the ABO-incompatible group and 16% for the ABO-compatible group (relative risk, 1.98; 95% confidence interval, 1.25 to 3.13). The positive group in the Crossmatch Study had fewer graft failures, rejection failures, and rejection episodes than the negative group; however, these differences were not statistically significant. These studies demonstrate that, for high-risk patients who are immunosuppressed by topical steroid therapy and followed up according to the CCTS protocol: (1) neither HLA-A, -B nor HLA-DR antigen matching substantially reduces the likelihood of corneal graft failure; (2) a positive donor-recipient crossmatch does not dramatically increase the risk of corneal graft failure; and (3) ABO blood group matching, which can be achieved with relatively little effort and expense, may be effective in reducing the risk of graft failure. C1 JOHNS HOPKINS UNIV HOSP,WILMER OPHTHALMOL INST,CTR COORDINATING,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,WILMER OPHTHALMOL INST,CENT LAB,BALTIMORE,MD 21205. NEI,BETHESDA,MD 20892. WK KELLOGG EYE CTR,ANN ARBOR,MI. UNIV MICHIGAN,TISSUE TYPING LAB,ANN ARBOR,MI 48109. MICHIGAN EYE BANK & TRANSPLANTAT CTR,ANN ARBOR,MI. EMORY EYE CTR,ATLANTA,GA. EMORY UNIV HOSP,HLA LAB,ATLANTA,GA 30322. GEORGIA LIONS EYE BANK,ATLANTA,GA. JOHNS HOPKINS UNIV,IMMUNOGENET LAB,BALTIMORE,MD 21218. MED EYE BANK MARYLAND,BALTIMORE,MD. DUKE UNIV,CTR EYE,DURHAM,NC 27706. VET AFFAIRS MED CTR,TRANSPLANT LAB,BALTIMORE,MD. CAROLINA ORGAN PROCUREMENT AGCY,BALTIMORE,MD. ESTELLE DOHENY EYE FDN,LOS ANGELES,CA 90033. UNIV CALIF LOS ANGELES,TISSUE TYPING LAB,LOS ANGELES,CA 90024. LIONS DOHENY EYE BANK,LOS ANGELES,CA. LOMA LINDA EYE BANK,LOS ANGELES,CA. MED EYE & TISSUE BANK ORANGE CTY,LOS ANGELES,CA. UNIV WISCONSIN,SCH MED,MADISON,WI 53706. UNIV WISCONSIN,TISSUE TYPING LAB,MADISON,WI 53706. WISCONSIN EYE BANK,MADISON,WI. NR 50 TC 228 Z9 232 U1 0 U2 3 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 OCT PY 1992 VL 110 IS 10 BP 1392 EP 1403 PG 12 WC Ophthalmology SC Ophthalmology GA JT349 UT WOS:A1992JT34900015 ER PT J AU LOCKSHIN, MD LETENDRE, CH AF LOCKSHIN, MD LETENDRE, CH TI ANTIPHOSPHOLIPID ANTIBODY LUPUS ANTICOAGULANT WORKSHOP SO ARTHRITIS AND RHEUMATISM LA English DT Article C1 NHLBI,BETHESDA,MD 20892. RP LOCKSHIN, MD (reprint author), NIAMSD,BLDG 31,ROOM 4C-32,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1992 VL 35 IS 10 BP 1234 EP 1237 DI 10.1002/art.1780351017 PG 4 WC Rheumatology SC Rheumatology GA JT648 UT WOS:A1992JT64800016 PM 1384513 ER PT J AU HUMPHREY, SM AF HUMPHREY, SM TI INDEXING BIOMEDICAL DOCUMENTS - FROM THESAURAL TO KNOWLEDGE-BASED RETRIEVAL-SYSTEMS SO ARTIFICIAL INTELLIGENCE IN MEDICINE LA English DT Article DE BIOMEDICAL LITERATURE; EXPERT SYSTEMS; FRAME DATA STRUCTURE; INFORMATION RETRIEVAL; KNOWLEDGE-BASED SYSTEMS; SUBJECT INDEXING; THESAURI ID EXPERT SYSTEM; CLASSIFICATION; ABSTRACTS; SOFTWARE; PROJECT AB This position paper advocates interactive knowledge-based indexing of the National Library of Medicine's (NLM's) MEDLINE database. Initially, it establishes that in the current setting concept indexing is needed and cannot be fully automated. Compatibility between conventional and knowledge-based indexing is then highlighted, followed by discussion of indexing as a cognitive process. The section on knowledge-based indexing systems describes how NLM's MedIndEx prototype addresses problems in conventional indexing, and includes the contention that constructing a knowledge base adapted from a conventional classified thesaurus and indexing scheme is not as daunting as it may seem. Extension of the indexing prototype to an intelligent search assistant illustrates use of the same knowledge base to integrate indexing and retrieval applications. The paper concludes with selections from the Milstead report on the state of the art of subject analysis for large multidisciplinary bibliographic databases, followed by suggested future directions for knowledge-based indexing. C1 NATL LIB MED,BETHESDA,MD 20894. NR 72 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0933-3657 J9 ARTIF INTELL MED JI Artif. Intell. Med. PD OCT PY 1992 VL 4 IS 5 BP 343 EP 371 DI 10.1016/0933-3657(92)90020-P PG 29 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA JX618 UT WOS:A1992JX61800003 ER PT J AU WITKIN, JM GOLDBERG, SR AF WITKIN, JM GOLDBERG, SR TI EFFECTS OF D-AMPHETAMINE, WIN-35,428, PENTOBARBITAL AND MORPHINE ON SCHEDULE-CONTROLLED RESPONDING IN 2 INBRED RAT STRAINS THAT DIFFER IN LOCOMOTOR STIMULATORY EFFECTS OF COCAINE SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE D-AMPHETAMINE; FIXED INTERVAL SCHEDULE; MORPHINE; PENTOBARBITAL; RAT STRAINS; WIN-35,428 ID MICE; BEHAVIOR; ANALOGS; DRUGS; REINFORCEMENT; APOMORPHINE AB Behavioral effects of d-amphetamine, the cocaine analog, WIN 35,428, morphine, and pentobarbital were compared in NBR/NIH and F344CR1BR rats. Either nose-poke or lever-press responding was maintained under 3-min fixed-interval schedules of food presentation. The effects of morphine, WIN 35,428 and pentobarbital depended upon the rat strain studied: morphine increased nose-poke responding in NBR but not F344 rats; significant strain x dose interactions were observed with WIN 35,428; and pentobarbital was more potent in decreasing nose-poke responding in NBR than in F344 rats. No strain differences were observed in the behavioral effects of d-amphetamine. There were also prominent differences in the effects of drugs that were related to the nature of the response requirement. In both rat strains, nose-poke responding was affected differently than lever-press responding by morphine, d-amphetamine, and WIN 35,428. Pentobarbital produced effects that were independent of the specified response topography. A global underlying difference in these rat strains cannot be identified at present to account for the diversity of findings. The behavioral effects of these drugs appear to be influenced by a host of interactive factors including the drug, strain of animal, the baseline response rate and physical dimensions of the response. C1 NIDA,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,BALTIMORE,MD. NR 27 TC 1 Z9 1 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD OCT PY 1992 VL 3 IS 5 BP 455 EP 463 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JW304 UT WOS:A1992JW30400004 ER PT J AU DAWID, IB AF DAWID, IB TI MESODERM INDUCTION AND AXIS DETERMINATION IN XENOPUS-LAEVIS SO BIOESSAYS LA English DT Review ID ACTIVIN-A; NEURAL INDUCTION; GROWTH-FACTORS; EARLY RESPONSE; EMBRYOS; DIFFERENTIATION; EXPRESSION; ORGANIZER; HOMOLOG; IDENTIFICATION AB In Xenopus, as in all amphibians and possibly in vertebrate embryos in general, mesoderm formation and the establishment of the dorsoventral axis depend on inductive cell interactions. Molecules involved in mesoderm induction include FGF which acts predominantly as a ventrolateral inducer, the TGF-beta homolog activin which can induce all types of mesoderm, and members of the Wnt family which have powerful dorsalizing effects. Early effects of inducer action include the activation of regulatory genes. Among such genes, particular interest is focused on three genes encoding putative transcription factors that are expressed specifically in the Spemann organizer region of the gastrula. Expression of one of these genes, goosecoid, has been shown to be sufficient to elicit the formation of a dorsal axis including head and notochord in the embryo. RP DAWID, IB (reprint author), NICHHD,BLDG 6B,RM 413,BETHESDA,MD 20892, USA. NR 45 TC 16 Z9 16 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 0265-9247 J9 BIOESSAYS JI Bioessays PD OCT PY 1992 VL 14 IS 10 BP 687 EP 691 DI 10.1002/bies.950141009 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA JW747 UT WOS:A1992JW74700005 PM 1365880 ER PT J AU LESCH, KP MANJI, HK AF LESCH, KP MANJI, HK TI SIGNAL-TRANSDUCING G-PROTEINS AND ANTIDEPRESSANT DRUGS - EVIDENCE FOR MODULATION OF ALPHA-SUBUNIT GENE-EXPRESSION IN RAT-BRAIN SO BIOLOGICAL PSYCHIATRY LA English DT Article ID GLIOMA C6 CELLS; 5-HT1A RECEPTOR RESPONSIVITY; COUPLED ADENYLATE-CYCLASE; GTP-BINDING PROTEIN; CHRONIC EXPOSURE; BETA-ADRENOCEPTORS; CEREBRAL-CORTEX; PHOSPHOLIPASE-C; MESSENGER-RNAS; DESIPRAMINE AB Signal-transducing G proteins, heterotrimers formed of alpha, beta, and gamma subunits, are central to the coordination of receptor-effector communication. They are derived from a large gene family, and recent cloning and sequencing of cDNAs encoding the a subunits, which confer receptor and effector specificity on the heterotrimer, have defined four major classes, G(s), G(i), G(q), and G12, with at least 16 isotypes. The G proteins that coordinate receptor-effector activity are especially important in the central nervous system (CNS), where they serve widespread, critical roles in the regulation of neuronal function, maintain the functional balance between neurotransmitter systems, and, as such, represent attractive potential targets for antidepressant drugs. We describe an integrated series of animal and cell culture studies aimed at testing the hypothesis that alterations in G protein function may contribute the complex neuroadaptive mechanisms involved in the clinical actions of antidepressants, and demonstrate that long-term administration of a wide spectrum of antidepressant drugs regulate Galpha(s), Galpha(i1), Galpha(i2), Galpha(o), Galpha(q), and Galpha12 mRNA and protein expression in various areas of the rat brain. Additionally, we present the polymerase chain reaction-(PCR) mediated cross-species partial cDNA cloning and sequencing of rat and human Galpha(o) and rat Galpha12, illustrate the regional distribution of Galpha mRNA and protein in rat brain, and provide evidence that different classes of antidepressants alter expression and/or stability of the recently identified Galpha12 mRNA. We conclude that long-term treatment with antidepressant drugs exerts differential effects on Galpha mRNA and protein expression in rat brain, thus modifying signal transduction as an integral part of complex neuroadaptive mechanisms that may underlie their therapeutic efficacy. The development of novel drugs with G proteins as primary targets remains an attractive prospect for the future. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL LAB,BETHESDA,MD 20892. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 70 TC 77 Z9 80 U1 1 U2 1 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 OCT 1 PY 1992 VL 32 IS 7 BP 549 EP 579 DI 10.1016/0006-3223(92)90070-G PG 31 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JZ805 UT WOS:A1992JZ80500001 PM 1333286 ER PT J AU CHEN, YD CHALOVICH, JM AF CHEN, YD CHALOVICH, JM TI A MOSAIC MULTIPLE-BINDING MODEL FOR THE BINDING OF CALDESMON AND MYOSIN SUBFRAGMENT-1 TO ACTIN SO BIOPHYSICAL JOURNAL LA English DT Article ID SMOOTH-MUSCLE CALDESMON; CHICKEN GIZZARD CALDESMON; SKELETAL F-ACTIN; ATPASE ACTIVITY; HEAVY-MEROMYOSIN; MOLECULAR-WEIGHT; CROSS-LINKING; ANALYTICAL ULTRACENTRIFUGATION; NH2-TERMINAL SEGMENT; THIN-FILAMENTS AB Binding of caldesmon to actin causes a decrease in the quantity of bound myosin and results in a reduction in the rate of actin-activated adenosine triphosphate hydrolysis. It is generally assumed that the binding of caldesmon and myosin to actin is a pure competitive interaction. However, recent binding studies of enzyme digested caldesmon subfragments directed at mapping the actin binding site of caldesmon have shown that a small 8-kD fragment around the COOH-terminal can compete directly with the myosin subfragment 1 (S-1) binding to actin; at least one other fragment that binds to actin does not inhibit the actin-activated adenosine triphosphate activity of myosin. That is, only a part of the caldesmon sequence may be responsible for directly blocking the binding of S-1 to actin. This prompts us to question the actual mode of binding of intact caldesmon and myosin S-1 to actin: whether the entire intact caldesmon molecule is competing with S-1 binding (pure competitive model) or just a small part of it (mosaic multiple-binding model). To answer this question, we measured the amount of myosin S-1 and caldesmon bound per actin monomer as a function of the total concentration of S-1 added to the system at constant concentrations of actin and caldesmon. A formalism for calculating the titration data based on the pure competitive model and a mosaic multiple-binding model was then developed. When compared with theoretical calculations, it is found that the binding of caldesmon and S-1 to actin cannot be pure competitive if no cooperativity exists between S-1 and caldesmon. In contrast, the mosaic multiple-binding model can fit the binding data rather well regardless of the existence of cooperativity between S-1 and caldesmon. C1 E CAROLINA UNIV,SCH MED,DEPT BIOCHEM,GREENVILLE,NC 27858. RP CHEN, YD (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. OI Chalovich, Joseph/0000-0002-1243-4055 FU NIAMS NIH HHS [AR35216, AR40540-01A1] NR 55 TC 23 Z9 24 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 OCT PY 1992 VL 63 IS 4 BP 1063 EP 1070 PG 8 WC Biophysics SC Biophysics GA JU251 UT WOS:A1992JU25100021 PM 1420925 ER PT J AU MINTON, AP AF MINTON, AP TI CONFINEMENT AS A DETERMINANT OF MACROMOLECULAR STRUCTURE AND REACTIVITY SO BIOPHYSICAL JOURNAL LA English DT Article ID DIFFUSION; VOLUME; MOLECULES; CYTOPLASM; CELLS AB The confinement of macromolecules within enclosures or "pores" of comparable dimensions results in significant size- and shape-dependent alterations Of macromolecular chemical potential and reactivity. Calculations of the magnitude of this effect for model particles of different shapes in model enclosures of different shapes were carried out using hard particle partition theory developed by Giddings et al. (J. Phys. Chem. 1968. 72:4397-4408). Results obtained indicate that the equilibrium constants of reactions, such as isomerization, self-association, and site binding, that result in significant change in macromolecular size, shape, and/or mobility may be altered within pores by as much as several orders of magnitude relative to the value in the unbounded or bulk phase. Confinement also produces a substantial size-dependent outward force on the walls of an enclosure. These results are likely to be important within the fluid phase of biological media, such as the cytoplasm of eukaryotic cells, containing significant volume fractions of large fibrous structures (e.g., the cytomatrix). RP MINTON, AP (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 13 TC 125 Z9 127 U1 1 U2 16 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1992 VL 63 IS 4 BP 1090 EP 1100 PG 11 WC Biophysics SC Biophysics GA JU251 UT WOS:A1992JU25100024 PM 1420928 ER PT J AU KALKO, SG CACHAU, RE SILVA, AM AF KALKO, SG CACHAU, RE SILVA, AM TI ION CHANNELS IN ICOSAHEDRAL VIRUS - A COMPARATIVE-ANALYSIS OF THE STRUCTURES AND BINDING-SITES AT THEIR FIVEFOLD AXES SO BIOPHYSICAL JOURNAL LA English DT Article ID BEAN MOSAIC-VIRUS; TOBACCO NECROSIS VIRUS; 3-DIMENSIONAL STRUCTURE; MOLECULAR COMPLEXES; CRYSTAL-STRUCTURE; 3.0-A RESOLUTION; MENGO-VIRUS; REFINEMENT; CATIONS; CRYSTALLIZATION AB An analysis of the crystallographically determined structures of the icosahedral protein coats of Tomato Bushy Stunt Virus, Southern Bean Mosaic Virus, Satellite Tobacco Necrosis Virus, Human Rhinovirus 14 and Mengovirus around their fivefold axes is presented. Accessibilities surfaces, electrostatic energy profile calculations, ion-protein interaction energy calculations, free energy perturbation methods and comparisons with structures of chelating agents are used in this study. It is concluded that the structures built around the viral fivefold axes would be adequate f or ion binding and transport. Relative ion preferences are derived f or the binding sites, using free energy perturbation methods, which are consistent with the experimental data when available. In the cases where crystallographic studies determined the existence of ions on the fivefold axes, our results indicate that they would correspond to ions in crystallization or purification buffers. The environment of the fivefold axes are rich in polar residues in all icosahedral viral structures whose atomic coordinates are available, including some that are not being analyzed in detail in this work. The fivefold channel-like structures have most of the basic properties expected for real ion channels including a funnel at the entrance, a polar internal environment with frequent alternation of acidic and basic residues, ion binding sites, the capability to induce ion dehydration and ion transit from the external viral surface to the binding sites. C1 NATL UNIV LA PLATA,FAC CIENCIAS EXACTAS,DEPT FIS,RA-1900 LA PLATA,ARGENTINA. PRI DYN CORP,CTR BIOMED SUPERCOMP,STRUCT BIOCHEM LAB,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. INST INVEST BIOQUIM,RA-8000 BAHIA BLANCA,ARGENTINA. OI Kalko, Susana/0000-0002-6701-0233 FU NCI NIH HHS [N01CO-74102] NR 59 TC 10 Z9 10 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 OCT PY 1992 VL 63 IS 4 BP 1133 EP 1145 PG 13 WC Biophysics SC Biophysics GA JU251 UT WOS:A1992JU25100027 PM 1384743 ER PT J AU JACCHIERI, SG JERNIGAN, RL AF JACCHIERI, SG JERNIGAN, RL TI VARIABLE RANGES OF INTERACTIONS IN POLYPEPTIDE CONFORMATIONS WITH A METHOD TO COMPLEMENT MOLECULAR MODELING SO BIOPOLYMERS LA English DT Article ID PROTEINS; TESTS AB Formulations of conformational weights for helix-coil transitions can be extended to substantially more complex situations than are usually pursued. General rules for matrix multiplication that depend parametrically on the interaction ranges and numbers of rotamers of residues are presented. The orders of the matrices of statistical weights can be increased with chain length, so that an individual matrix element can represent any specified single conformation, as needed. By the appropriate choice of interaction ranges and numbers of available conformers, approximations can be introduced in which: (1) an average of the conformations of any chain segment is obtained, (2) specific residue-residue interactions are excluded, or (3) the conformation of a part of the chain is restricted or fixed. The method is appropriate for treating specific interactions in peptides and could be used together with available experimental information to develop models of conformational transitions. As such, the methods represent a class of calculations aimed at more rigorous calculations built around known features of a molecule. The aim is to facilitate calculations that bridge the gap between nonquantitative molecular model building and more rigorous but less directed molecular mechanics calculations. The method can directly include any desired longer range of interactions, if the interaction range is not too long to make impossible the manipulation of the requisite matrices. An outline is presented of an application to treat salt bridges in the C peptide of ribonuclease A. C1 NCI,DCBDC,MATH BIOL LAB,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012 NR 10 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD OCT PY 1992 VL 32 IS 10 BP 1327 EP 1338 DI 10.1002/bip.360321007 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JN001 UT WOS:A1992JN00100006 PM 1420961 ER PT J AU ZIMMERMAN, SB MURPHY, LD AF ZIMMERMAN, SB MURPHY, LD TI EXCLUDED VOLUME EFFECTS ON THE PARTITION OF SINGLE-STRANDED AND DOUBLE-STRANDED OLIGODEOXYNUCLEOTIDES BETWEEN 2 LIQUID-PHASES SO BIOPOLYMERS LA English DT Article ID SIZE FRACTIONATION; DNA FRAGMENTS; MACROMOLECULES; CHROMATOGRAPHY AB The distribution coefficients of single- and double-stranded oligodeoxynucleotides in a PEG 8000/phosphate two-phase system are a function of their chain length. Values of the distribution coefficients are in general agreement with a simple extension of a model for excluded volume effects (the "available volume model") which was applied previously to the distribution of proteins in this system. The current results therefore provide a second set of examples for molecules of very different geometry where the distribution of added molecules is controlled by excluded volume interactions between those molecules and the PEG 8000 of the two-phase system. RP ZIMMERMAN, SB (reprint author), NIDDKS,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 29 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD OCT PY 1992 VL 32 IS 10 BP 1365 EP 1373 DI 10.1002/bip.360321010 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JN001 UT WOS:A1992JN00100009 PM 1420964 ER PT J AU HAUN, RS SERVENTI, IM MOSS, J AF HAUN, RS SERVENTI, IM MOSS, J TI RAPID, RELIABLE LIGATION-INDEPENDENT CLONING OF PCR PRODUCTS USING MODIFIED PLASMID VECTORS SO BIOTECHNIQUES LA English DT Note ID NUCLEOTIDE; DNA RP HAUN, RS (reprint author), NHLBI,CELLULAR METAB LAB,BLDG 10,RM 5N307,BETHESDA,MD 20892, USA. NR 6 TC 71 Z9 78 U1 2 U2 15 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1992 VL 13 IS 4 BP 515 EP 518 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR498 UT WOS:A1992JR49800006 PM 1362067 ER PT J AU ALDROUBI, A GARNER, MM AF ALDROUBI, A GARNER, MM TI MINIMAL ELECTROPHORESIS TIME FOR DNA SEQUENCING SO BIOTECHNIQUES LA English DT Article ID CAPILLARY ELECTROPHORESIS; RESOLUTION; SEPARATION AB This study presents a mathematical approach that allows one to determine the shortest electrophoresis time and migration path length required for DNA sequencing. The calculation was applied to the capillary electrophoresis of a DNA sequencing separation and showed that acceptable resolution could be obtained using a shorter path length than anticipated. C1 NICHHD,BETHESDA,MD 20892. RP ALDROUBI, A (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Aldroubi, Akram/J-7186-2012 NR 8 TC 11 Z9 11 U1 1 U2 3 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1992 VL 13 IS 4 BP 620 EP 624 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JR498 UT WOS:A1992JR49800031 PM 1476732 ER PT J AU HORNUNG, RL KIERTSCHER, SM MATHEWS, HL AF HORNUNG, RL KIERTSCHER, SM MATHEWS, HL TI SYSTEMIC IL-1 AND ADJUVANT TREATMENT OF AN EXPERIMENTAL TUMOR .1. IMMUNE STATUS FOLLOWING TUMOR RECHALLENGE SO BIOTHERAPY LA English DT Article DE ANTITUMOR ACTIVITY; CANCER THERAPY; RECOMBINANT INTERLEUKIN-1-ALPHA ID T-CELLS; HUMAN INTERLEUKIN-1-BETA; SYNGENEIC TUMORS; LYMPHOID-CELLS; MICE; INVIVO; LYMPHOCYTES; RESTORATION; REACTIVITY; INDUCTION AB Local adjuvant therapy of weakly immunogenic tumors protects against primary tumor challenge. However, this form of therapy does not produce long-lasting immunity to the tumor. In this study, local adjuvant therapy combined with systemic IL-1 administration produced not only primary tumor protection, but also long lasting immunity to the tumor. IL-1 and adjuvant protected animals resisted rechallenge with tumor as much as 180 days after initial tumor administration. Resistance to tumor rechallenge was IL-1 dose dependent. IL-1 and adjuvant protected animals also exhibited delayed type hypersensitivity reactions which were tumor-specific. Splenic and lymph node cell populations from IL-1 and adjuvant protected animals mounted tumor-specific lymphoproliferative responses. No such responses were observed in animals which had been administered either IL-1 or adjuvant alone. These results demonstrate that systemic IL-1 functions to augment specific immune protection when administered in conjunction with local adjuvant, resulting in long-lasting tumor immunity. C1 LOYOLA UNIV,STRITCH SCH MED,DEPT MICROBIOL & IMMUNOL,2160 S 1ST AVE,MAYWOOD,IL 60153. NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,CLIN IMMUNOL SERV,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO-74102] NR 29 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-299X J9 BIOTHERAPY JI Biotherapy PD OCT PY 1992 VL 5 IS 3 BP 227 EP 237 DI 10.1007/BF02171055 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA JV908 UT WOS:A1992JV90800007 PM 1419470 ER PT J AU ANDERSON, PM OCHOA, AC RAMSAY, NKC HASZ, D WEISDORF, D AF ANDERSON, PM OCHOA, AC RAMSAY, NKC HASZ, D WEISDORF, D TI ANTI-CD3+ INTERLEUKIN-2 STIMULATION OF MARROW AND BLOOD - COMPARISON OF PROLIFERATION AND CYTOTOXICITY SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BONE-MARROW; T-CELLS; TUMOR-CELLS; TRANSPLANTATION; ANTIBODY; THERAPY; MICE; ACTIVATION; GRAFT C1 UNIV MINNESOTA,CEREBROVASC PROGRAM,MINNEAPOLIS,MN 55455. NCI,FREDERICK CANC RES CTR,FREDERICK,MD 21701. FU NCI NIH HHS [P01-CA21737] NR 44 TC 13 Z9 13 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 OCT 1 PY 1992 VL 80 IS 7 BP 1846 EP 1853 PG 8 WC Hematology SC Hematology GA JQ374 UT WOS:A1992JQ37400028 PM 1391948 ER PT J AU HEYES, MP SAITO, K CROWLEY, JS DAVIS, LE DEMITRACK, MA DER, M DILLING, LA ELIA, J KRUESI, MJP LACKNER, A LARSEN, SA LEE, K LEONARD, HL MARKEY, SP MARTIN, A MILSTEIN, S MOURADIAN, MM PRANZATELLI, MR QUEARRY, BJ SALAZAR, A SMITH, M STRAUSS, SE SUNDERLAND, T SWEDO, SW TOURTELLOTTE, WW AF HEYES, MP SAITO, K CROWLEY, JS DAVIS, LE DEMITRACK, MA DER, M DILLING, LA ELIA, J KRUESI, MJP LACKNER, A LARSEN, SA LEE, K LEONARD, HL MARKEY, SP MARTIN, A MILSTEIN, S MOURADIAN, MM PRANZATELLI, MR QUEARRY, BJ SALAZAR, A SMITH, M STRAUSS, SE SUNDERLAND, T SWEDO, SW TOURTELLOTTE, WW TI QUINOLINIC ACID AND KYNURENINE PATHWAY METABOLISM IN INFLAMMATORY AND NONINFLAMMATORY NEUROLOGICAL DISEASE SO BRAIN LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; SIMIAN IMMUNODEFICIENCY VIRUS; INFECTED RHESUS MACAQUES; CHRONIC FATIGUE SYNDROME; CEREBROSPINAL-FLUID; HUNTINGTONS-DISEASE; INDOLEAMINE 2,3-DIOXYGENASE; RAT-BRAIN; TRYPTOPHAN-METABOLITES; ALZHEIMERS-DISEASE AB Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized froM L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus. particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,CLIN PHARMACOL SECT,BETHESDA,MD 20892. NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. NIH,DEPT NUCL MED,BETHESDA,MD 20892. NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. VET ADM MED CTR,NEUROL SERV,ALBUQUERQUE,NM 87108. CALIF REG PRIMATE CTR,DAVIS,CA. CTR DIS CONTROL,CTR INFECT DIS,ATLANTA,GA 30333. GEORGE WASHINGTON UNIV,DEPT NEUROL,WASHINGTON,DC 20052. WALTER REED ARMY MED CTR,DEPT NEUROL,WASHINGTON,DC 20307. NEUROL & RES SERV,LOS ANGELES,CA. NATL NEUROL BANK,LOS ANGELES,CA. UNIV MANITOBA,DEPT PEDIAT & CHILD HLTH,WINNIPEG R3T 2N2,MANITOBA,CANADA. RP HEYES, MP (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,ROOM 3D40,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI martin, alex/B-6176-2009; Demitrack, Mark/I-7697-2013; OI Mouradian, M. Maral/0000-0002-9937-412X FU NCRR NIH HHS [RR00039] NR 73 TC 446 Z9 453 U1 2 U2 30 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 1992 VL 115 BP 1249 EP 1273 DI 10.1093/brain/115.5.1249 PN 5 PG 25 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JY715 UT WOS:A1992JY71500001 PM 1422788 ER PT J AU DUHAMEL, JR GOLDBERG, ME FITZGIBBON, EJ SIRIGU, A GRAFMAN, J AF DUHAMEL, JR GOLDBERG, ME FITZGIBBON, EJ SIRIGU, A GRAFMAN, J TI SACCADIC DYSMETRIA IN A PATIENT WITH A RIGHT FRONTOPARIETAL LESION - THE IMPORTANCE OF COROLLARY DISCHARGE FOR ACCURATE SPATIAL-BEHAVIOR SO BRAIN LA English DT Article ID VISUALLY GUIDED SACCADES; SUPERIOR COLLICULUS; EYE-MOVEMENTS; ATTENTION; MONKEY; CORTEX; RESPONSES; NEURONS; MACAQUE; FIELDS AB Double-step experiments have demonstrated that retinotopic coding is inadequate to explain the spatial performance of the saccadic system. In such experiments a subject is asked to make two successive saccades to fixate two sequentially flashed targets each of which disappears before the first saccade. Despite the dissonance thus created between the retinal location of the second target and the saccade necessary to acquire it, normal humans and monkeys perform the task perfectly well. Single unit recording in monkeys indicates that neurons in the superior colliculus, frontal eye fields and in parietal cortex generate a spatially accurate signal during the performance of double-step saccades, which is thought to be obtained by combining a retinotopic signal with a signal corollary to the previous saccadic eye movement. We studied saccadic eye movements in a patient with a right fronto-parietal lesion using single- and double-step tasks. Single saccades into the left (contralesional) hemifield had longer latency and were hypometric relative to those into the right (ipsilesional) hemifield. Varying the initial orbital position had no effect on the latency and accuracy of saccades to left and right retinal stimuli. When the patient was asked to do a double-step task with targets flashed first into the right field and then into the left field, she performed well. When she was asked to do the same task with a target flashed first into the left field and then into the right field she made the first saccade correctly but never acquired the second target, even though this required her to make a saccade in the normal direction to a stimulus that appeared in the normal field. Such a deficit therefore cannot be one of retinotopic or spatial coding, nor can it be one of generating a certain direction of saccade. We suggest that the deficit is a failure of corollary discharge, the inability to register the amplitude and direction of a saccade into the contralesional field, and use that information to update the representation of the location of the next saccade target. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. NINCDS,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. NR 25 TC 138 Z9 138 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 1992 VL 115 BP 1387 EP 1402 DI 10.1093/brain/115.5.1387 PN 5 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JY715 UT WOS:A1992JY71500008 PM 1422794 ER PT J AU FRIEDMAN, RB FERGUSON, S ROBINSON, S SUNDERLAND, T AF FRIEDMAN, RB FERGUSON, S ROBINSON, S SUNDERLAND, T TI DISSOCIATION OF MECHANISMS OF READING IN ALZHEIMERS-DISEASE SO BRAIN AND LANGUAGE LA English DT Article ID DEMENTIA; ACTIVATION; ALOUD; WORK C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT SPEECH & HEARING,WASHINGTON,DC 20052. NIMH,CLIN SCI LAB,GERIATR PSYCHOPHARMACOL UNIT,BETHESDA,MD 20892. NR 13 TC 43 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 1992 VL 43 IS 3 BP 400 EP 413 DI 10.1016/0093-934X(92)90109-R PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA JV154 UT WOS:A1992JV15400003 PM 1446210 ER PT J AU KREUTZBERG, GW KLATZO, I KLEIHUES, P AF KREUTZBERG, GW KLATZO, I KLEIHUES, P TI VOGT,OSKAR AND VOGT,CECILE, LENIN BRAIN AND THE BUMBLEBEES OF THE BLACK-FOREST SO BRAIN PATHOLOGY LA English DT Note AB Oskar Vogt (1870-1955) was a prominent German neurologist and neuroanatomist with a strong interest in the pathogenesis of brain diseases. Together with his wife Cecile (1875-1962), he published landmark papers on the cyto- and myelo-architecture of the brain and the functional anatomy of the basal ganglia. He developed the concept of pathoclisis, i.e., the selective vulnerability of specific neuronal populations in the CNS. In the 1920's, Vogt created a multi-disciplinary brain research institute, the Kaiser-Wilhelm-Institut fur Hirnforschung in Berlin-Buch. After Lenin's death in 1924, Oskar Vogt was called to Moscow where he formed a new brain research institute, with the main purpose to investigate the revolutionary's brain. After being dismissed from office by the Nazi government in 1937, the Vogts continued their work in a privately funded institute in Neustadt, the Black Forest. C1 NIH,BETHESDA,MD 20892. UNIV HOSP ZURICH,INST NEUROPATHOL,CH-8091 ZURICH,SWITZERLAND. RP KREUTZBERG, GW (reprint author), MAX PLANCK INST PSYCHIAT,DEPT NEUROMORPHOL,W-8033 MARTINSRIED,GERMANY. NR 20 TC 10 Z9 10 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 1992 VL 2 IS 4 BP 363 EP 371 DI 10.1111/j.1750-3639.1992.tb00712.x PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA JR602 UT WOS:A1992JR60200010 PM 1341969 ER PT J AU HUGHES, AL AF HUGHES, AL TI THE PREVALENCE OF ILLICIT DRUG-USE IN 6 METROPOLITAN-AREAS IN THE UNITED-STATES - RESULTS FROM THE 1991-NATIONAL-HOUSEHOLD-SURVEY-ON-DRUG-ABUSE SO BRITISH JOURNAL OF ADDICTION LA English DT Note AB National levels and trends of illicit drug use in the general population are well documented. However, little is known about how this phenomenon is distributed among various subnational areas such as state, metropolitan area, and other local areas. The sample design from the National Household Survey on Drug Abuse (NHSDA) was recently expanded such that estimates from several large metropolitan areas could be produced with reasonable precision. The prevalence of illict drug use is examined in six large metropolitan areas of the United States. These findings indicate that, in some cases, drug use varies considerably by metropolitan area. RP HUGHES, AL (reprint author), NIDA,DIV EPIDEMIOL & PREVENT RES,5600 FISHERS LANE,ROCKWALL 2 BLDG,SUITE 615,ROCKVILLE,MD 20857, USA. NR 2 TC 10 Z9 10 U1 0 U2 1 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD OCT PY 1992 VL 87 IS 10 BP 1481 EP 1485 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA JT833 UT WOS:A1992JT83300012 PM 1422110 ER PT J AU BEVAN, KA NEWMAN, AH BOWERY, NG TORTELLA, FC AF BEVAN, KA NEWMAN, AH BOWERY, NG TORTELLA, FC TI MECHANISM OF THE ANTICONVULSANT ACTION OF DEXTROMETHORPHAN ANALOGS IN RAT-BRAIN SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 UNIV LONDON,DEPT PHARMACOL,LONDON WC1N 1AX,ENGLAND. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NR 4 TC 2 Z9 2 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD OCT PY 1992 VL 107 SU S BP P62 EP P62 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JR252 UT WOS:A1992JR25200062 ER PT J AU WEIGHT, FF FAN, P VISENTIN, S AF WEIGHT, FF FAN, P VISENTIN, S TI COCAINE ANTAGONIZES 5-HT ACTIVATION OF 5-HT3 CHANNELS IN NEURONS FROM RAT NODOSE GANGLION SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,ROCKVILLE,MD 20852. RI Visentin, Sergio/G-9779-2016 OI Visentin, Sergio/0000-0001-8510-6987 NR 2 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD OCT PY 1992 VL 107 SU S BP P12 EP P12 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JR252 UT WOS:A1992JR25200012 ER PT J AU BREIER, A SCHREIBER, JL DYER, J PICKAR, D AF BREIER, A SCHREIBER, JL DYER, J PICKAR, D TI COURSE OF ILLNESS AND PREDICTORS OF OUTCOME IN CHRONIC-SCHIZOPHRENIA - IMPLICATIONS FOR PATHOPHYSIOLOGY SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL SYMP ON SCHIZOPHRENIA ON TRANSACTIONAL PROCESSES IN THE DEVELOPMENT AND COURSE OF SCHIZOPHRENIC DISORDERS CY OCT, 1990 CL UNIV BERN, PSYCHIAT CLIN, BERN, SWITZERLAND HO UNIV BERN, PSYCHIAT CLIN ID VENTRICULAR BRAIN ENLARGEMENT; SEVERE MENTAL-ILLNESS; LONG-TERM; FOLLOW-UP; PREFRONTAL CORTEX; NEGATIVE SYMPTOMS; NATURAL-HISTORY; PATHOLOGY; SIZE; METHODOLOGY C1 NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. YALE UNIV,SCH NURSING,NEW HAVEN,CT 06520. RP BREIER, A (reprint author), UNIV MARYLAND,SCH MED,MARYLAND PSYCHIAT RES CTR,DEPT OUTPATIENT,POB 21247,CATONSVILLE,MD 21228, USA. NR 43 TC 21 Z9 21 U1 1 U2 2 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 OCT PY 1992 VL 161 SU 18 BP 38 EP 43 PG 6 WC Psychiatry SC Psychiatry GA JT654 UT WOS:A1992JT65400006 ER PT J AU GERACI, MF UHDE, TW AF GERACI, MF UHDE, TW TI DIURNAL RHYTHMS AND SYMPTOM SEVERITY IN PANIC DISORDER - A PRELIMINARY-STUDY OF 24-HOUR CHANGES IN PANIC ATTACKS, GENERALIZED ANXIETY, AND AVOIDANCE-BEHAVIOR SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID DEPRESSION; PEOPLE AB Diurnal changes in the frequency of panic attacks and symptoms of generalised anxiety, phobic anxiety and phobic avoidance in 34 panic-disorder patients and 40 normal controls were evaluated. The panic-disorder patients had significant diurnal changes in generalised and phobic anxiety, but not phobic avoidance. Increased severity of symptoms and prominent diurnal changes were most evident in the panic-disorder patients with a history of depression. Although panic attacks were distributed throughout the 24-hour period, patients with a current episode or history of depression tended to have more frequent panic attacks in the morning or early afternoon. These observations challenge the traditional belief that 'anxious neurotic' patients are relatively asymptomatic upon awakening in the morning and then develop more severe symptoms of anxiety later in the day. C1 NIMH,INTRAMURAL RES PROGRAM,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NURSING,MHAN & A NURSING SERV,MENTAL HLTH CLIN,BETHESDA,MD 20892. NR 16 TC 10 Z9 10 U1 0 U2 1 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 OCT PY 1992 VL 161 BP 512 EP 516 DI 10.1192/bjp.161.4.512 PG 5 WC Psychiatry SC Psychiatry GA JR505 UT WOS:A1992JR50500010 PM 1393338 ER PT J AU JABLONSKI, S AF JABLONSKI, S TI SYNDROME - A CHANGING CONCEPT SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Syndrome is one of the oldest terms in the medical vocabulary. Traditionally, the term has been used mainly as a designation for complex medical entities, such as multiple abnormalities, that are characterized by clusters of concurring symptoms, usually three or more. During the mid-twentieth century, the meaning and the use of the term were altered. First to take place was an attempt to eliminate physicians' names from syndrome nomenclature, resulting in a significant increase in the use of descriptive designations in proportion to eponyms. But the trend was counterbalanced by the creation of new classes of eponyms. Eponymous syndrome nomenclature now includes the names of literary characters, patients' surnames, subjects of famous paintings, famous persons, geographic locations, institutions, biblical figures, and mythological characters. This was followed by a relaxation in the scope of the definition of syndrome, wherein the term could also be used as a modifier indicating a special (sometimes unspecified) complexity of an already named pathological condition. Eventually syndrome changed from its original use as an exclusively medical term and came to mean anything unusual, abnormal, bizarre, or humorous, whether medical, social, behavioral, or cultural. This unrestrained use of the term is the principal cause of an enormous volume of the sometimes irrelevant syndrome literature cluttering databases in the MEDLARS system and of the deterioration of "SYNDROME" as a specific MeSH term and a useful search parameter. C1 NATL LIB MED,INDEXING,BETHESDA,MD 20209. NR 12 TC 8 Z9 10 U1 0 U2 1 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA STE 300, 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1992 VL 80 IS 4 BP 323 EP 327 PG 5 WC Information Science & Library Science SC Information Science & Library Science GA JT353 UT WOS:A1992JT35300001 PM 1422501 ER PT J AU HSIEH, RKC GAMBOA, CA AF HSIEH, RKC GAMBOA, CA TI USING BITNET TO ACCESS THE NATIONAL LIBRARY OF MEDICINE DATABASES SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB An ongoing developmental project is described that uses the National Library of Medicine (NLM) GRATEFUL MED software on the BITNET network to access the NLM databases. The objective of the project is to improve biomedical communication capabilities to support health professionals in countries where international telecommunication services are limited. After a successful demonstration of the concept, the system was assembled and tested by the University of Chile and NLM. The full impact of this project will be measured at a later time. This paper describes the concept and testing of the system in Latin American countries. C1 PAN AMER HLTH ORG,HUMAN RESOURCES PROGRAM,WASHINGTON,DC 20037. RP HSIEH, RKC (reprint author), NATL LIB MED,INT PROGRAMS,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA STE 300, 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1992 VL 80 IS 4 BP 335 EP 338 PG 4 WC Information Science & Library Science SC Information Science & Library Science GA JT353 UT WOS:A1992JT35300003 PM 1422503 ER PT J AU SOEHNER, CB WRAY, ST RICHARDS, DT AF SOEHNER, CB WRAY, ST RICHARDS, DT TI THE LANDMARK CITATION METHOD - ANALYSIS OF A CITATION PATTERN AS A COLLECTION ASSESSMENT METHOD SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB The landmark citation method is a new collection assessment method based on the citation record of a single landmark article. This citation record is developed by identifying sources which cite the landmark article. A bibliography, extracted from the citation record, is then used to complete an assessment of the collection. This method was developed and used to assess the biotechnology collection of the National Library of Medicine. The information gained from this study, in addition to demonstrating the technique, also provided insight into the evolution of the biotechnology literature. C1 NATL AGR LIB,CIRCULAT SECT,BELTSVILLE,MD 20705. NATL AGR LIB,REG DOCUMENT DELIVERY SYST,BELTSVILLE,MD 20705. DARTMOUTH COLL,BIOMED LIB,HANOVER,NH 03755. RP SOEHNER, CB (reprint author), NATL LIB MED,MEDLARS MANAGEMENT SECT,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. OI Soehner, Catherine/0000-0001-7259-2496 NR 8 TC 2 Z9 2 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA STE 300, 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1992 VL 80 IS 4 BP 361 EP 366 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA JT353 UT WOS:A1992JT35300008 PM 1422507 ER PT J AU DWIGGINS, S HARDING, BJ AF DWIGGINS, S HARDING, BJ TI THE NATURE OF PDQ SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Letter RP DWIGGINS, S (reprint author), NCI,CTR INT CANC INFORMAT,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA STE 300, 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1992 VL 80 IS 4 BP 382 EP 382 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA JT353 UT WOS:A1992JT35300014 PM 1422513 ER PT J AU HOWSER, DM AF HOWSER, DM TI COMPREHENSIVE CANCER NURSING REVIEW - GROENWALD,SL, FROGGE,MH, GOODMAN,M, YARBRO,CH SO CANCER NURSING LA English DT Book Review RP HOWSER, DM (reprint author), NCI,DEPT CANC TREATMENT,COP,MED BRANCH,PROTOCOL OFF,BETHESDA,MD 20892, USA. NR 1 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 OCT PY 1992 VL 15 IS 5 BP 382 EP 382 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA JV347 UT WOS:A1992JV34700009 ER PT J AU LEE, GH MERLINO, G FAUSTO, N AF LEE, GH MERLINO, G FAUSTO, N TI DEVELOPMENT OF LIVER-TUMORS IN TRANSFORMING GROWTH FACTOR-ALPHA TRANSGENIC MICE SO CANCER RESEARCH LA English DT Article ID HEPATOCELLULAR-CARCINOMA; TGF-ALPHA; PARTIAL-HEPATECTOMY; EPITHELIAL-CELLS; MOUSE-LIVER; RAT; REGENERATION; CARCINOGENESIS; EXPRESSION; RECEPTOR AB We studied the development of liver tumors in male transforming growth factor alpha (TGF-alpha) transgenic mice of the CD1 strain and examined the expression of the transgene by immunohistochemistry and in situ hybridization. Livers of 4-5-week-old transgenic mice contained areas of centribobular hypertrophy with low glucose-6-phosphatase activity. These areas progressively expanded, and hypertrophy and dysplasia became generalized in livers of mice at 10-12 months of age. The expression of the transgene, determined by either immunohistochemistry or in situ hybridization, was uneven in animals that were 10 weeks old or older. The positive hepatocytes formed patches with a predominant centrilobular distribution. We studied a total of 23 liver tumors (7 hepatocellular carcinomas and 16 adenomas) obtained from 11 mice at 13-15 months of age and from one 7-month-old animal which received zinc sulfate to induce the transgene. The carcinomas were well differentiated tumors, without glucose-6-phosphatase or gamma-glutamyltranspeptidase activity, that developed from the dysplastic parenchyma and occasionally within an adenoma. In all carcinomas and in 56% of the adenomas there was overexpression of the transgene in relationship to the surrounding tissue. The majority of the tumors that overexpressed TGF-alpha were alpha-fetoprotein positive, while alpha-fetoprotein staining was not detected in tumors (all adenomas) that did not show excessive transgene expression. We conclude that TGF-alpha functions as a promoter of liver carcinogenesis through its effect as an autocrine inducer of hepatocyte proliferation. Further, the data indicate that TGF-alpha overexpression may favor tumor progression. C1 BROWN UNIV,DEPT PATHOL & LAB MED,BOX G,PROVIDENCE,RI 02912. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA23226] NR 68 TC 149 Z9 151 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 OCT 1 PY 1992 VL 52 IS 19 BP 5162 EP 5170 PG 9 WC Oncology SC Oncology GA JQ455 UT WOS:A1992JQ45500004 PM 1327502 ER PT J AU TAKAGI, H SHARP, R HAMMERMEISTER, C GOODROW, T BRADLEY, MO FAUSTO, N MERLINO, G AF TAKAGI, H SHARP, R HAMMERMEISTER, C GOODROW, T BRADLEY, MO FAUSTO, N MERLINO, G TI MOLECULAR AND GENETIC-ANALYSIS OF LIVER ONCOGENESIS IN TRANSFORMING GROWTH FACTOR-ALPHA TRANSGENIC MICE SO CANCER RESEARCH LA English DT Article ID WOODCHUCK HEPATITIS-VIRUS; MAMMARY EPITHELIAL-CELLS; FACTOR-II PRECURSOR; HA-RAS ONCOGENE; C-MYC; FACTOR RECEPTOR; HEPATOCELLULAR-CARCINOMA; MESSENGER-RNA; TGF-ALPHA; MOUSE AB Overexpression of a transforming growth factor alpha (TGF-alpha) transgene induced the development of liver tumors in 69 of 93 (74%) adult male mice. To identify factors associated with oncogenesis, liver tumors from transgenic animals were characterized at the molecular level. TGF-alpha RNA transcripts were elevated in 17 of 25 (68%) liver tumors, relative to adjacent nontumorous tissue. Expression of the endogenous c-myc and insulin-like growth factor II genes was enhanced in 7 of 19 (37%) and 12 of 16 (75%) tumors, respectively. In contrast, epidermal growth factor receptor RNA levels were unchanged or reduced in all liver tumors. and mutations were not detected in either the Ha-ras or Ki-ras genes. The occurrence of liver tumors in castrated TGF-alpha transgenic mice was reduced about 7-fold, while in ovariectomized transgenic animals the incidence was increased about 6-fold. The progeny of a cross between CD1-derived TGF-alpha transgenic (MT42) and C57BL/6 mice exhibited no reduction in tumor burden (83%); however, the incidence of tumor formation in MT42 x FVB/N offspring was substantially lower (19%). We conclude that in these transgenic mice TGF-alpha promotes tumor formation and appears to play a major role in tumor progression. Moreover, other factors that may collaborate in TGF-alpha-induced hepatocarcinogenesis include c-myc, insulin-like growth factor II, sex hormones, and the genetic background upon which the transgene operates. C1 NCI, MOLEC BIOL LAB, 9000 ROCKVILLE PIKE, 36-1D28, BETHESDA, MD 20892 USA. MERCK SHARP & DOHME LTD, W POINT, PA 19486 USA. BROWN UNIV, DEPT PATHOL & LAB MED, PROVIDENCE, RI 02912 USA. NR 74 TC 101 Z9 101 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1992 VL 52 IS 19 BP 5171 EP 5177 PG 7 WC Oncology SC Oncology GA JQ455 UT WOS:A1992JQ45500005 PM 1394122 ER PT J AU NASONBURCHENAL, K WOLFF, L AF NASONBURCHENAL, K WOLFF, L TI INVOLVEMENT OF THE SPLEEN IN PRELEUKEMIC DEVELOPMENT OF A MURINE RETROVIRUS-INDUCED PROMONOCYTIC LEUKEMIA SO CANCER RESEARCH LA English DT Article ID C-MYB; BALB/C MICE; TUMORS; CELLS; CLASSIFICATION; EXPRESSION; ONCOGENES AB An acute myeloid leukemia can result from the inoculation of Moloney murine leukemia virus into BALB/c mice undergoing a 2,6,10,14-tetramethylpentadecane-induced chronic inflammatory response in the peritoneal cavity. This leukemia is ultimately observed in the peritoneal cavity as an ascites with cells infiltrating the granulomatous tissue. It has been proposed, however, that hematopoietic organs such as the spleen and bone marrow are involved in preleukemic development of Moloney murine leukemia. Therefore, to determine if the spleen plays a role in this development, mice were splenectomized at various times relative to virus inoculation. When splenectomies were performed 3 days before and 2, 4, 6, and 8 weeks after virus inoculation there was, in all cases, a decreased death rate compared to sham-splenectomized controls. The greatest difference in death rate due to promonocytic leukemia was observed when mice were splenectomized at 4 weeks after virus inoculation. The decrease in disease incidence observed as a result of splenectomy was not caused by decreased virus spread in hematopoietic organs or an alteration in the profile of the cellular infiltrate in the granuloma. It was found, however, that the spleens of 2,6,10,14-tetramethylpentadecane-treated mice, relative to those of normal mice, have a significantly increased number of granulocyte-macrophage colony-forming cells and a slightly increased number of multipotential colony-forming cells. These observations suggest that a population of target cells for transformation, consisting of granulocyte-macrophage precursor cells, may reside in the spleen. Alternatively, partially transformed cells may reside temporarily in the spleen during the developmental stages of the disease process. C1 NCI,GENET LAB,BLDG 37,ROOM 2B04,BETHESDA,MD 20892. CATHOLIC UNIV AMER,DEPT BIOL,WASHINGTON,DC 20064. NR 17 TC 10 Z9 10 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 OCT 1 PY 1992 VL 52 IS 19 BP 5317 EP 5322 PG 6 WC Oncology SC Oncology GA JQ455 UT WOS:A1992JQ45500028 PM 1394137 ER PT J AU WIKENHEISER, KA CLARK, JC LINNOILA, RI STAHLMAN, MT WHITSETT, JA AF WIKENHEISER, KA CLARK, JC LINNOILA, RI STAHLMAN, MT WHITSETT, JA TI SIMIAN VIRUS-40 LARGE T-ANTIGEN DIRECTED BY TRANSCRIPTIONAL ELEMENTS OF THE HUMAN SURFACTANT PROTEIN-C GENE PRODUCES PULMONARY ADENOCARCINOMAS IN TRANSGENIC MICE SO CANCER RESEARCH LA English DT Article ID LUNG-CANCER; EXPRESSION; P53; TUMORS; CARCINOGENESIS; ABNORMALITIES; LOCALIZATION; ONCOGENES; MUTATIONS; FREQUENT AB A model of pulmonary adenocarcinomas was produced in transgenic mice harboring a chimeric gene comprising the SV40 large T antigen under the control of a transcriptional region derived from the human surfactant protein C (SP-C) gene. Transgenic mice succumbed with pulmonary tumors within 4-5 months of age. By histology, the tumors were adenocarcinomas with lepidic, papillary, and solid growth patterns that were indistinguishable from adenocarcinomas occurring in humans. Immunocytochemistry demonstrated the lack of staining for neuroendocrine markers, consistent with the identification of the tumors as non-small cell rather than small cell carcinomas. The presence of SV40 large T mRNA in the lung and tumors was detected by in situ hybridization and Northern blot analysis. Exogenous SV40 large T mRNA and endogenous CC10 (a nonciliated respiratory epithelial cell marker) and SP-C (a Type II alveolar cell marker) mRNAs were expressed at variable levels in the lung tumors. SV40 large T mRNA and CC10 mRNA were detected in the majority of tumors, while SP-C mRNA was detected less frequently. The heterogeneity of bronchiolar and alveolar cell markers in the tumors from the transgenic mice supports the concept that tumorigenesis was initiated in distinct subsets of epithelial cells that produce characteristic adenocarcinomas of the lung. C1 CHILDRENS HOSP RES FDN,DIV PULM BIOL,ELLAND & BETHESDA AVE,CINCINNATI,OH 45229. VANDERBILT UNIV,DIV NEONATOL,NASHVILLE,TN 37240. NCI,BIOMARKERS & PREVENT RES BRANCH,KENSINGTON,MD 20895. FU NHLBI NIH HHS [HL 41496] NR 44 TC 97 Z9 99 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 OCT 1 PY 1992 VL 52 IS 19 BP 5342 EP 5352 PG 11 WC Oncology SC Oncology GA JQ455 UT WOS:A1992JQ45500032 PM 1394139 ER PT J AU ZAVITSANOS, X HATZAKIS, A KAKLAMANI, E TZONOU, A TOUPADAKI, N BROEKSMA, C CHRISPEELS, J TROONEN, H HADZIYANNIS, S HSIEH, CC ALTER, H TRICHOPOULOS, D AF ZAVITSANOS, X HATZAKIS, A KAKLAMANI, E TZONOU, A TOUPADAKI, N BROEKSMA, C CHRISPEELS, J TROONEN, H HADZIYANNIS, S HSIEH, CC ALTER, H TRICHOPOULOS, D TI ASSOCIATION BETWEEN HEPATITIS-C VIRUS AND HEPATOCELLULAR-CARCINOMA USING ASSAYS BASED ON STRUCTURAL AND NONSTRUCTURAL HEPATITIS-C VIRUS PEPTIDES SO CANCER RESEARCH LA English DT Article ID NON-B-HEPATITIS; NON-A; POSTTRANSFUSION HEPATITIS; ANTIBODY TESTS; UNITED-STATES; LIVER-DISEASE; DELTA-AGENT; PREVALENCE; INFECTION; CIRRHOSIS AB Stored sera from 181 Greek patients with hepatocellular carcinoma (HCC), 35 patients with metastatic liver cancer, and 416 hospital controls with diagnoses other than malignant neoplasm or liver disease were examined with first and second generation hepatitis C virus (HCV) enzyme immunoassays as well as with five HCV supplemental assays based on structural and nonstructural HCV peptides. Second generation HCV enzyme immunoassays were more sensitive than first generation assays. However, both assays had suboptimal specificity using the standard reactivity criterion (absorbance of sample to cutoff greater-than-or-equal-to 1.0). Specificity was improved by centrifugation and by using a sample's optical density to cutoff ratio greater-than-or-equal-to 3.0 or supplemental assays; in this instance the prevalence of antibodies to HCV was 13.3% (24 of 181), 0 (0 of 35), and 1.4% (6 of 416) in HCC, metastatic liver cancer, and hospital controls, respectively. A similar estimation of prevalence of antibody to HCV in HCC (12.5% or 4 of 32) was obtained when the recombinant immunoblot assay, second generation, was used to screen a random sample of HCC patients. The relative risk linking HCV to HCC was estimated as 10.4 (95% confidence interval, 4.2-26.0; P < 0.0001). These data suggest that the prevalence of antibodies to HCV in HCC using stored sera has been previously overestimated even though the evidence of a causal association of HCV with HCC persists. C1 UNIV ATHENS, SCH MED, DEPT HYG & EPIDEMIOL, M ASIAS 75, GR-11527 ATHENS, GREECE. UNIV ATHENS, SCH MED, DEPT EPIDEMIOL, ATHENS, GREECE. UNIV ATHENS, HIPPOKRAT GEN HOSP, ACAD DEPT MED, ATHENS, GREECE. ABBOTT GMBH DIAGNOST, W-6200 WIESBADEN, GERMANY. NIH, WARREN G MAGNUSON CLIN CTR, DEPT TRANSFUS MED, BETHESDA, MD 20892 USA. NR 48 TC 30 Z9 28 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1992 VL 52 IS 19 BP 5364 EP 5367 PG 4 WC Oncology SC Oncology GA JQ455 UT WOS:A1992JQ45500035 PM 1382842 ER PT J AU DEBINSKI, W PASTAN, I AF DEBINSKI, W PASTAN, I TI MONOVALENT IMMUNOTOXIN CONTAINING TRUNCATED FORM OF PSEUDOMONAS EXOTOXIN AS POTENT ANTITUMOR AGENT SO CANCER RESEARCH LA English DT Article ID RICIN-A CHAIN; ANTI-TRANSFERRIN RECEPTOR; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODIES; INVIVO THERAPY; BINDING; TUMOR; DEGLYCOSYLATION; AERUGINOSA; FRAGMENTS AB Recombinant truncated forms of Pseudomonas exotoxin A that lack the cell binding domain of Pseudomonas exotoxin A were coupled to an F(ab') fragment of a monoclonal antibody HB21 directed against the human transferrin receptor. One of these was NlysPE40. The other, NlysPE38QQR, has two amino groups on residues near the NH2-terminus and has no amino groups near the COOH-terminus. The proteins were linked by a stable thioether bond that connected the sulfhydryl group present in the hinge region of the antibody fragment to an amino group on the toxin. The F(ab')-PE40 immunotoxin, containing NlysPE40, exhibited potent cytotoxic activity on human carcinoma cell lines with a concentration of immunotoxin at which isotope incorporation falls by 50% when compared to nontreated cells (ID50) of 5.3 pM (0.5 ng/ml) on both the epidermoid carcinoma A431 and on the colon carcinoma Colo205. Immunotoxins made with whole antibody were considerably less active, with an ID50 of 15.9 pM (3.1 ng/ml) on these cell lines. F(ab')-PE38QQR, the immunotoxin containing NlysPE38QQR, was found to be the most active agent with an ID50 of 1.05 pM (0.1 ng/ml) on A431 cells. The greater cytotoxicity of immunotoxins containing fragmented antibody was probably due to the higher binding affinity of F(ab') conjugates in comparison to whole antibody conjugates to the transferrin receptor. The increase in cytotoxic activity of the immunotoxin made with NlysPE38QQR than that with NlysPE40 may reflect selective coupling of the toxin through NH2-terminal amino groups. The monovalent and divalent immunotoxins had dose-dependent antitumor effects on human epidermoid carcinoma xenografts in nude mice. A431 tumors completely regressed in all animals at a total dose of 105 pmol (10 mug) of F(ab')-PE38QQR and of 154 pmol (30 mug) of IgG-PE38QQR. Furthermore, the F(ab') immunotoxin was less toxic to mice than the conjugate containing IgG (840 pmol or 80 mug of total dose causing measurable adverse effects versus 208 pmol or 40 mug, respectively). Thus, a truncated Pseudomonas exotoxin A molecule coupled to the F(ab') fragment of an antibody is more active and less toxic in mice than an immunotoxin made with a whole antibody. Therefore, the therapeutic index for the monovalent immunotoxin is about four times better than that for the divalent immunotoxin. C1 NCI,DIV CANC BIOL & DIAG CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 32 TC 30 Z9 30 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 OCT 1 PY 1992 VL 52 IS 19 BP 5379 EP 5385 PG 7 WC Oncology SC Oncology GA JQ455 UT WOS:A1992JQ45500038 PM 1394141 ER PT J AU BLAIR, A LINOS, A STEWART, PA BURMEISTER, LF GIBSON, R EVERETT, G SCHUMAN, L CANTOR, KP AF BLAIR, A LINOS, A STEWART, PA BURMEISTER, LF GIBSON, R EVERETT, G SCHUMAN, L CANTOR, KP TI COMMENTS ON OCCUPATIONAL AND ENVIRONMENTAL-FACTORS IN THE ORIGIN OF NON-HODGKINS-LYMPHOMA SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI AB The review of the literature regarding non-Hodgkin's lymphoma and occupational and environmental factors presented at this workshop suggested associations with viruses, solvents, and hair dyes. A population-based case-control study among men from Iowa and Minnesota notes similar associations. Workers engaged in metal working, hair care, painting, and dry cleaning experienced nonsignificant excesses. Risks from specific exposures showed some variation by histological type. Both follicular and diffuse non-Hodgkin's lymphoma were associated with benzene. The diffuse type was linked to solvents other than benzene and formaldehyde, while the follicular was excessive among workers exposed to oils and greases. C1 UNIV ATHENS,DEPT EPIDEMIOL,ATHENS,GREECE. UNIV IOWA,DEPT PREVENT MED,IOWA CITY,IA 52242. ORLANDO REG MED CTR INC,DEPT INTERNAL MED,ORLANDO,FL 32806. UNIV MINNESOTA,DEPT EPIDEMIOL,MINNEAPOLIS,MN 55455. RP BLAIR, A (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,ROCKVILLE,MD 20892, USA. NR 5 TC 33 Z9 34 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5501 EP S5502 PG 2 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800021 ER PT J AU BOICE, JD AF BOICE, JD TI RADIATION AND NON-HODGKINS-LYMPHOMA SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID CANCER RISK; MULTIPLE-MYELOMA; BOMB SURVIVORS; MORTALITY; LEUKEMIA; RADIOTHERAPY; WORKERS; I-131 AB Lymphomas are rarely, if ever, found to be in excess following exposure to ionizing radiation. Hodgkin's disease has never bee, linked to radiation, and the evidence for non-Hodgkin's lymphoma (NHL) is very weak. Low doses of radiation from diagnostic X-ray procedures or from occupational exposures do not appear to cause NHL. Mortality studies of atomic bomb survivors in Japan and other epidemiological studies with quantitative estimates of radiation dose also fail to find dose-response relationships. NHL may arise infrequently following high-dose, possibly near lethal, radiation treatments. Immunosuppression associated with the disease being treated, such as Hodgkin's disease, may contribute to the development of NHL. If radiation does not cause NHL, at least not by its accepted mechanism of action of breaking chromosomes, creating rearrangements, gene deletions, and mutations, perhaps other environmental mutagens and clastogens should not be considered likely causes of NHL. RP BOICE, JD (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 24 TC 35 Z9 35 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5489 EP S5491 PG 3 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800018 ER PT J AU DEVESA, SS FEARS, T AF DEVESA, SS FEARS, T TI NON-HODGKINS-LYMPHOMA TIME TRENDS - UNITED-STATES AND INTERNATIONAL DATA SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI AB Incidence data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute, earlier incidence surveys, and the International Agency for Research on Cancer, mortality data from the National Center for Health Statistics, and population data from the Census Bureau were used to assess rates of non-Hodgkin's lymphoma. Mortality and incidence rates have been increasing for many years. Larger increases among older persons suggest a role for improving diagnosis, particularly during the 1950s and 1960s. Urban/rural and socioeconomic differences have diminished over time. Since the early 1970s, incidence rates increased at 3-4%/year, more rapidly than for all other cancers except melanoma of the skin and lung cancer among women. Incidence rates increased over all ages except the very young, among whites and blacks, in geographic areas both in the United States and internationally, and both sexes. During the 1980s, the impact of AIDS is apparent among young and middle-aged men. Differences in non-Hodgkin's lymphoma rates persist between races and sexes. Increases have been more marked for extranodal disease, particularly those arising in the brain, and for high-grade tumors. Explanations accounting for all the increases in rates are not readily available. RP DEVESA, SS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. NR 18 TC 301 Z9 306 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5432 EP S5440 PG 9 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800004 PM 1394149 ER PT J AU HARTGE, P DEVESA, SS AF HARTGE, P DEVESA, SS TI QUANTIFICATION OF THE IMPACT OF KNOWN RISK-FACTORS ON TIME TRENDS IN NON-HODGKINS-LYMPHOMA INCIDENCE SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID MORTALITY AB The incidence of non-Hodgkin's lymphoma among white men in the United States was measured as 6.9/100,000 person-years in 1947-1950 and as 17.4 in 1984-1988. We have estimated how much the known and suspected diagnostic and risk factors might have contributed to this apparent increase of 152%. Firm conclusions cannot be drawn without more data on risk and changes in prevalence, but a reasonable range of impacts can be constructed. After accounting for the likely effects of misdiagnosis of Hodgkin's disease as non-Hodgkin's lymphoma, of the acceptance of new entities of non-Hodgkin's lymphoma, of familial factors, of human immunodeficiency virus and other immunosuppressive conditions or drugs, and of occupation, we estimate that the percentage increase in incidence was still 80% among all males and 42% among those aged 0-64. An agent carrying a relative risk of 2.0 rising in prevalence from 0 to 42% would account for the latter rise. Diet, hair dyes, and general environmental exposures to pesticides may be contributing, but currently estimated risks and changes in exposure levels do not appear large enough to account for the residual rise. Among men aged 75-84, some of the residual rise of 109% probably is diagnostic, but only further research will clarify the issue. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. RP HARTGE, P (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN 443,BETHESDA,MD 20892, USA. NR 24 TC 139 Z9 141 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5566 EP S5569 PG 4 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800036 ER PT J AU HOOVER, RN AF HOOVER, RN TI LYMPHOMA RISKS IN POPULATIONS WITH ALTERED IMMUNITY - A SEARCH FOR MECHANISM SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI AB There have been numerous studies of lymphoma incidence in patient populations having diseases or taking medications that result in altered immunity. While many of these have uncovered substantially elevated risks, little has been done to use these observations to gain insights into the mechanisms of lymphomagenesis. Speculation about mechanism has centered on either immunosuppression or immunostimulation. The patterns of risk among kidney transplant recipients (higher risks for those receiving cadaveric grafts, having multiple transplants, or having received transplants in the earlier years of transplantation) favor the immunostimulation hypothesis. Likewise, the higher lymphoma risk associated with indices of increasing severity of disease among patients with sicca syndrome also support the role of immunostimulation over that of immunosuppression. However, an ordering of many of the more extensively studied conditions with altered immunity on the basis of the relative risk of lymphoma associated with these conditions reveals a pattern of risk which is not completely consistent with the level of either immune suppression or immune stimulation. Perhaps we have reached a point where epidemiologists working with laboratory and clinical immunologists can discern a more sophisticated underlying mechanism than the crude concepts of immunosuppression or immunostimulation that would explain the markedly differing lymphoma risks seen in various groups with marked immune abnormalities. If so, markers of more subtle alterations in this mechanism might be profitably explored for their role in lymphoma in general and as a tool to define the environmental causes of the epidemic increases. RP HOOVER, RN (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 4 TC 69 Z9 70 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5477 EP S5478 PG 2 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800014 PM 1394157 ER PT J AU JAFFE, ES RAFFELD, M MEDEIROS, LJ STETLERSTEVENSON, M AF JAFFE, ES RAFFELD, M MEDEIROS, LJ STETLERSTEVENSON, M TI AN OVERVIEW OF THE CLASSIFICATION OF NON-HODGKINS-LYMPHOMAS - AN INTEGRATION OF MORPHOLOGICAL AND PHENOTYPICAL CONCEPTS SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID SMALL LYMPHOCYTIC LYMPHOMA; EPSTEIN-BARR-VIRUS; B-CELL LYMPHOMA; NATIONAL-CANCER-INSTITUTE; MANTLE-ZONE LYMPHOMA; MALIGNANT-LYMPHOMAS; INTERMEDIATE DIFFERENTIATION; LYMPHOBLASTIC LYMPHOMA; IMMUNOLOGICAL PHENOTYPES; FOLLICULAR LYMPHOMAS AB An analysis of trends in the incidence of non-Hodgkin's lymphoma requires an understanding of individual disease entities within this broad group. The non-Hodgkin's lymphomas represent a diverse group of malignancies that have in common an origin from lymphoid cells. Nevertheless, these disorders are heterogeneous in their clinical behavior, morphological appearance, cellular origin, etiology, and pathogenesis. A modern classification of non-Hodgkin's lymphomas must include an integration of morphological, immunophenotypical, and molecular concepts in order to delineate individual diseases within this broad group. Existing classification schemes such as the working formulation, while they may be useful in providing a guide to clinical management, cannot provide this information in the absence of other data. This point is most readily made with the low-grade B-cell lymphomas which include follicular lymphomas, mantle cell lymphomas, small lymphocytic lymphomas, immunosecretory disorders, and lymphomas of mucosa-associated lymphoid tissues. Each of these malignancies has a distinct phenotype and genotype, and indubitably each has a different etiology. The postthymic T-cell tumors are equally diverse. Analysis of epidemiological data from cancer registries must include a recognition that our ability to recognize individual diseases from historical data is limited. Studies of trends in the non-Hodgkin's lymphomas should attempt to delineate biological markers that may be of relevance to pathogenesis in both historical and prospectively accrued cases. RP JAFFE, ES (reprint author), NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892, USA. NR 58 TC 36 Z9 36 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5447 EP S5452 PG 6 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800007 ER PT J AU KIRSCH, IR LIPKOWITZ, S AF KIRSCH, IR LIPKOWITZ, S TI A MEASURE OF GENOMIC INSTABILITY AND ITS RELEVANCE TO LYMPHOMAGENESIS SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID FUNCTIONAL RECEPTORS; CELL; IMMUNOGLOBULIN; RECOMBINATION; EXPRESSION; INVERSION; CANCER; GENES; LOCI AB A recent pilot study that we performed on 12 individuals who are involved in the cultivation and processing of grains and legumes suggests to us that we may have in hand a relatively quick, inexpensive, and highly sensitive assay that identifies individuals at increased risk for the development of lymphoid malignancy. The generation of this assay evolved from our interest in the causes and consequences of lymphocyte-specific chromosomal aberration. RP KIRSCH, IR (reprint author), NCI,NAVY MED ONCOL BRANCH,8901 WISCONSIN AVE,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. NR 16 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1992 VL 52 IS 19 SU S BP S5545 EP S5546 PG 2 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800029 ER PT J AU LEVINE, AM SHIBATA, D SULLIVANHALLEY, J NATHWANI, B BRYNES, R SLOVAK, ML MAHTERIAN, S RILEY, CL WEISS, L LEVINE, PH RASHEED, S BERNSTEIN, L AF LEVINE, AM SHIBATA, D SULLIVANHALLEY, J NATHWANI, B BRYNES, R SLOVAK, ML MAHTERIAN, S RILEY, CL WEISS, L LEVINE, PH RASHEED, S BERNSTEIN, L TI EPIDEMIOLOGIC AND BIOLOGICAL STUDY OF ACQUIRED IMMUNODEFICIENCY SYNDROME-RELATED LYMPHOMA IN THE COUNTY-OF-LOS-ANGELES - PRELIMINARY-RESULTS SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID EPSTEIN-BARR-VIRUS; NON-HODGKINS LYMPHOMAS; HOMOSEXUAL MEN; AIDS AB A population-based case control study of intermediate- and high-grade lymphoma in the County of Los Angeles, CA, was initiated in 1989. Human immunodeficiency virus (HIV)-positive lymphoma patients are compared to HIV-negative lymphoma patients, to HIV-positive controls with acquired immunodeficiency syndrome but without lymphoma, and to HIV-positive asymptomatic individuals. The HIV-negative lymphoma cases are compared to neighborhood controls, who are matched in terms of age, sex, race/ethnicity, and socioeconomic status. All cases are reviewed for pathology by a single group of pathologists. All cases and controls are studied for HIV, Epstein-Barr virus (EBV), and human herpesvirus 6 antigens and antibodies. Tissues from HIV-positive and -negative cases are studied for immunoglobulin gene rearrangement, presence of EBV and HIV, c-myc oncogene rearrangements, and karyotypic analysis. To date, with 294 lymphoma cases and 181 control cases interviewed, high-grade lymphoma has been diagnosed in 82% of the HIV-positive cases versus 40% of the HIV-negative cases (P = 0.001). Although elevated titers of EBV-viral capsid antigen were demonstrated in 82% of HIV-positive versus 50% of HIV-negative lymphoma cases, the geometric mean titer of EBV-viral capsid antigen is similar among HIV-positive lymphoma cases and HIV-positive controls. The geometric mean titer of human herpesvirus 6 antibodies was similar in HIV-positive and HIV-negative lymphoma cases and in the control populations. Monoclonality was demonstrated in all cases of lymphoma. EBV genome was demonstrated within lymphoma DNA in 68% of HIV-positive and 15% of HIV-negative lymphoma cases. Further study will be required to elucidate the full mechanisms of pathogenesis of the acquired immunodeficiency syndrome-related lymphomas. C1 UNIV SO CALIF,SCH MED,DEPT INTERNAL MED HEMATOL,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90033. UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. CITY HOPE NATL MED CTR,DUARTE,CA 91010. NCI,CANC EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 12 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1992 VL 52 IS 19 SU S BP S5482 EP S5484 PG 3 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800016 ER PT J AU LEVINE, PH AF LEVINE, PH TI APPLICATIONS OF EXPERIMENTAL-TECHNIQUES TO EPIDEMIOLOGIC STUDIES OF NON-HODGKINS-LYMPHOMA - USE OF ARCHIVAL TISSUES SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID EPSTEIN-BARR-VIRUS; CELL LEUKEMIA LYMPHOMA; DISEASE AB Archival tissues, particularly formalin-fixed paraffin-embedded tumors, have become increasingly valuable in studies of the etiology of cancer. In non-Hodgkin's lymphoma, subclassification of tumors by immunophenotyping and identification of oncogenic viruses has allowed more accurate interpretation of associated epidemiological information. One such example is adult T-cell leukemia/lymphoma, which is not a single histopathological entity and usually is associated with human T-cell lymphotropic virus, type I. In addition to confirming the diagnosis, the pattern of virus distribution, utilized recently in studies of Epstein-Barr virus and human herpesvirus-6-associated lymphoma, has suggested which tumors are more likely to have the virus playing a passenger role (virus detected in uninvolved tissues) and in which tumors the virus may have an etiological role (virus restricted to tumor cells). Preservation and cataloguing of tumors and relevant clinical and demographic data may play an increasingly important role in demographic studies. RP LEVINE, PH (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 19 TC 0 Z9 0 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5561 EP S5562 PG 2 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800034 ER PT J AU LEVINE, PH PETERSON, D MCNAMEE, FL OBRIEN, K GRIDLEY, G HAGERTY, M BRADY, J FEARS, T ATHERTON, M HOOVER, R AF LEVINE, PH PETERSON, D MCNAMEE, FL OBRIEN, K GRIDLEY, G HAGERTY, M BRADY, J FEARS, T ATHERTON, M HOOVER, R TI DOES CHRONIC FATIGUE SYNDROME PREDISPOSE TO NON-HODGKINS-LYMPHOMA SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID NATURAL-KILLER CELLS; EPSTEIN-BARR-VIRUS; BURKITTS-LYMPHOMA; SEQUENCES; CLUSTER AB Chronic fatigue syndrome, an illness that frequently is associated with abnormalities of cellular immunity, has been reported anecdotally to be associated with an increased incidence of lymphoid hyperplasia and malignancy. This report describes an initial analysis of population-based cancer incidence data in Nevada, focusing on the patterns of non-Hodgkin's lymphoma prior to and subsequent to well described, documented outbreaks of chronic fatigue syndrome during 1984-1986. In a study of time trends in four age groups, the observed time trends were consistent with the national trends reported in the Surveillance, Epidemiology, and End Results Program. No statistically significant increase attributable to the chronic fatigue syndrome outbreak was identified at the state level. Additional studies are in progress analyzing the data at the county level, reviewing patterns in other malignancies, and continuing to monitor the cancer patterns over subsequent years. C1 NEVADA CANC REGISTRY,RENO,NV 89520. RP LEVINE, PH (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 434,BETHESDA,MD 20892, USA. NR 29 TC 10 Z9 10 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5516 EP S5518 PG 3 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800024 ER PT J AU LEVY, R LEVINE BANKS, PM PEARCE JAFFE, ES BLAIR, A WEISENBURGER, DD MUELLER, NE CARTWRIGHT, RA ANDERSON ZAHM, SH OCONOR, G BOICE, JD AF LEVY, R LEVINE BANKS, PM PEARCE JAFFE, ES BLAIR, A WEISENBURGER, DD MUELLER, NE CARTWRIGHT, RA ANDERSON ZAHM, SH OCONOR, G BOICE, JD TI GENETIC AND ENVIRONMENTAL DETERMINANTS - DISCUSSION SO CANCER RESEARCH LA English DT Discussion C1 UNIV SO CALIF,SCH MED,DEPT INTERNAL MED HEMATOL,LOS ANGELES,CA 90033. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,ROCKVILLE,MD 20892. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. LOYOLA UNIV,SCH MED,MAYWOOD,IL 60153. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP LEVY, R (reprint author), STANFORD UNIV,MED CTR,DEPT MED,DIV ONCOL,STANFORD,CA 94305, USA. NR 2 TC 0 Z9 0 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5518 EP S5521 PG 4 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800025 ER PT J AU LINET, MS POTTERN, LM AF LINET, MS POTTERN, LM TI FAMILIAL AGGREGATION OF HEMATOPOIETIC MALIGNANCIES AND RISK OF NON-HODGKINS-LYMPHOMA SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID IMMUNODEFICIENCY; LEUKEMIA; DISEASE; YORKSHIRE; RELATIVES; CANCERS AB Examination of risk factors that may be responsible for the increasing incidence of non-Hodgkin's lymphoma (NHL) over the past few decades would be incomplete without considering familial aggregation of hematolymphoproliferative neoplasms and the relative contributions of heredity and environment to the etiology of NHL. Reports of families with two or more NHL cases and sometimes additional members affected by other hematopoietic malignancies (multiple-case families) are summarized, as are findings from surveys and quantitative risk estimates from population-based studies of familial aggregation. The notable occurrence of various immunological abnormalities among multiple-case family members with and without NHL or related neoplasms is underscored, as is the diversity of types of other lymphoproliferative and hematopoietic malignancies among close relatives in these families. Preliminary evidence suggesting that multiple-case families may be more susceptible to certain environmental exposures is presented. An international registry of such families (particularly those identified in population-based studies) is proposed to clarify the interrelationship of genetic, familial, and environmental factors in the etiology of NHL. RP LINET, MS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN 415B,ROCKVILLE,MD 20892, USA. NR 62 TC 42 Z9 43 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1992 VL 52 IS 19 SU S BP S5468 EP S5473 PG 6 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800012 PM 1394155 ER PT J AU MAGRATH, I AF MAGRATH, I TI MOLECULAR-BASIS OF LYMPHOMAGENESIS SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID T-CELL LEUKEMIA; HUMAN LYMPHOID MALIGNANCIES; EPSTEIN-BARR-VIRUS; P53 GENE; BURKITTS-LYMPHOMA; HEPATOCELLULAR-CARCINOMA; FOLLICULAR LYMPHOMA; CARRYING T(14-18); LONG REMISSION; PRE-B AB Lymphoid neoplasms, like all malignant tumors, arise as a consequence of the accumulation, in a single cell, of a set of genetic lesions that result in altered proliferation or increased clonal life span. The most frequently observed genetic abnormalities among the malignant non-Hodgkin's lymphomas are translocations, which appear to be lineage and, to a large extent, lymphoma specific. Recombinases that normally mediate the process of antigen receptor gene rearrangement appear to have an important (but not exclusive) role in the mediation of these translocations and of other types of gene fusion (e.g., deletion of intervening DNA). Frequently, such fusions result in the increased or inappropriate expression of crucially important proteins, many of which are transcription factors that regulate the expression of other genes. These abnormalities, however, do not appear to be sufficient to induce lymphoma, and it is likely that the additional genetic lesions required differ from one tumor to another. The likelihood of any given clone of cells accumulating a sufficient number of relevant genetic lesions to give rise to a lymphoma is probably a function of its life span. Prolonged survival of a cell clone may be mediated by viral genomes (e.g., Epstein-Barr virus and human T-cell leukemia/lymphoma virus type 1), by the abnormal expression of cellular genes that inhibit apoptosis (e.g., bcl-2), or by the mutation or deletion of cellular genes that are necessary for apoptosis, e.g., p53. The background rate at which genetic lesions occur is amplified by the interaction of inherited and environmental factors, the latter appearing to be the major determinant of incidence rates. However, inherited factors that influence lymphomagenesis, including variability in the ability to repair DNA damage or in the fidelity of antigen receptor recombinases for their signal sequences, may be crucial determinants of which particular individuals in a given environmental setting develop lymphoma. RP MAGRATH, I (reprint author), NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892, USA. NR 72 TC 49 Z9 49 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5529 EP S5540 PG 12 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800027 ER PT J AU MOSIER, DE MAGRATH, I KIRSCH, IR POTTER, M LEVY, R RABKIN TEW, JG JAFFE, ES WEISENBURGER, DD BLATTNER SZAKAL, AK BANKS, PM HOOVER, RN AF MOSIER, DE MAGRATH, I KIRSCH, IR POTTER, M LEVY, R RABKIN TEW, JG JAFFE, ES WEISENBURGER, DD BLATTNER SZAKAL, AK BANKS, PM HOOVER, RN TI MOLECULAR AND IMMUNOREGULATORY MECHANISMS - DISCUSSION SO CANCER RESEARCH LA English DT Discussion C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. NCI,DIV CANC BIOL & DIAG,GENET LAB,BETHESDA,MD 20892. STANFORD UNIV,MED CTR,DEPT MED,DIV ONCOL,STANFORD,CA 94305. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT ENTOMOL & NEMATOL,RICHMOND,VA 23298. NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP MOSIER, DE (reprint author), MED BIOL INST,LA JOLLA,CA 92037, USA. NR 0 TC 0 Z9 0 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5562 EP S5565 PG 4 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800035 ER PT J AU MUELLER, NE FRAUMENI, JF AF MUELLER, NE FRAUMENI, JF TI RESEARCH DIRECTIONS AND GENERAL DISCUSSION - A SUMMARY SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20892. RP MUELLER, NE (reprint author), HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1992 VL 52 IS 19 SU S BP S5571 EP S5571 PG 1 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800038 ER PT J AU OBRAMS, GI OCONOR, G AF OBRAMS, GI OCONOR, G TI TIME TRENDS AND PATHOLOGICAL CLASSIFICATION - A SUMMARY SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI C1 LOYOLA UNIV,SCH MED,MAYWOOD,IL 60153. RP OBRAMS, GI (reprint author), NCI,EXTRAMURAL PROGRAMS BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 8 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5570 EP S5570 PG 1 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800037 ER PT J AU PERCY ZAHM, SH CARTWRIGHT, RA OCONOR, G BANKS, PM HOOVER, RN ANDERSON BLAIR, A BLATTNER WEISENBURGER, DD JAFFE, ES BIGGAR DEVESA, SS HOLFORD, TR AF PERCY ZAHM, SH CARTWRIGHT, RA OCONOR, G BANKS, PM HOOVER, RN ANDERSON BLAIR, A BLATTNER WEISENBURGER, DD JAFFE, ES BIGGAR DEVESA, SS HOLFORD, TR TI TIME TRENDS AND PATHOLOGICAL CLASSIFICATION - DISCUSSION SO CANCER RESEARCH LA English DT Discussion C1 NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,ROCKVILLE,MD 20892. UNIV LEEDS,LEUKAEMIA RES FUND CTR CLIN EPIDEMIOL,DEPT PATHOL,LEEDS LS2 9NG,W YORKSHIRE,ENGLAND. LOYOLA UNIV,SCH MED,MAYWOOD,IL 60153. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5462 EP S5464 PG 3 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800010 ER PT J AU POTTER, M AF POTTER, M TI PATHOGENETIC MECHANISMS IN B-CELL NON-HODGKINS-LYMPHOMAS IN HUMANS SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID CHRONIC LYMPHOCYTIC-LEUKEMIA; C-MYC; FOLLICULAR LYMPHOMA; IMMUNE-DEFICIENCY; BCL-2 GENE; EXPRESSION; ONCOGENE; PROTEIN; MICE; TRANSLOCATIONS AB A very large proportion of non-Hodgkin's lymphoma in the United States are of B-cell origin. This group of tumors includes a variety of different pathological and clinical types. Chromosomal rearrangements play an important role in the pathogenesis of many of these tumors. In B-cells these translocation processes appear to develop as illegitimate products of physiological V-(D)-J or heavy chain switch rearrangements. The biology of the well-known chromosomal translocations is discussed. Additional biological factors in lymphomagenesis (aging, immunodeficiency, role of antigenic stimulation, and genetically determined susceptibility) are discussed. RP POTTER, M (reprint author), NCI,DIV CANC BIOL & DIAG,GENET LAB,BLDG 37,2B04,BETHESDA,MD 20892, USA. NR 73 TC 30 Z9 30 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5522 EP S5528 PG 7 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800026 ER PT J AU POTTER, M AF POTTER, M TI MOLECULAR AND IMMUNOREGULATORY MECHANISMS - A SUMMARY SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI RP POTTER, M (reprint author), NCI,GENET LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5572 EP S5572 PG 1 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800039 PM 1394178 ER PT J AU ZAHM, SH BLAIR, A AF ZAHM, SH BLAIR, A TI PESTICIDES AND NON-HODGKINS-LYMPHOMA SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON THE EMERGING EPIDEMIC OF NON-HODGKINS LYMPHOMA : CURRENT KNOWLEDGE REGARDING ETIOLOGICAL FACTORS CY OCT 22-23, 1991 CL BETHESDA, MD SP NCI ID SOFT-TISSUE SARCOMA; CANCER MORTALITY; MALIGNANT-LYMPHOMA; WESTERN WASHINGTON; HERBICIDE USE; EXPOSURE; CHLOROPHENOLS; WORKERS; RISK; FARMERS AB The incidence of non-Hodgkin's lymphoma (NHL) has increased over 50% in the last 15 years. This paper reviews the possible role of pesticides in this increase. While small increases in risk of NHL among farmers have been observed in general occupational surveys, recent studies focusing on specific pesticides have observed much larger risks. Frequent use of phenoxyacetic acid herbicides, in particular, 2,4-dichlorophenoxyacetic acid, has been associated with 2- to 8-fold increases of NHL in studies conducted in Sweden, Kansas, Nebraska, Canada, and elsewhere. Canine malignant lymphoma has also been associated with dog owner use of 2,4-dichlorophenoxyacetic acid and commercial lawn pesticide treatments. There are much fewer data linking NHL to other types of pesticides, but triazine herbicides, organophosphate insecticides, fungicides, and fumigants have also been associated with increased risk of NHL. Pesticide exposures are not limited to agricultural populations but are widespread in the general population through use on lawns, golf courses, rights-of-way, and elsewhere. Since the use of pesticides, particularly phenoxy herbicides, has increased dramatically preceding and during the time period in which the incidence of NHL has increased, they could have contributed to the rising incidence of NHL. RP ZAHM, SH (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 37 TC 121 Z9 122 U1 0 U2 9 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 OCT 1 PY 1992 VL 52 IS 19 SU S BP S5485 EP S5488 PG 4 WC Oncology SC Oncology GA JR138 UT WOS:A1992JR13800017 PM 1394159 ER PT J AU POTTER, M WIENER, F AF POTTER, M WIENER, F TI PLASMACYTOMAGENESIS IN MICE - MODEL OF NEOPLASTIC DEVELOPMENT DEPENDENT UPON CHROMOSOMAL TRANSLOCATIONS SO CARCINOGENESIS LA English DT Review ID C-MYC ONCOGENE; MURINE LEUKEMIA-VIRUS; HEAVY-CHAIN LOCUS; IMMUNOGLOBULIN SWITCH REGION; BALB/C SUBLINE DIFFERENCES; BINDING MYELOMA PROTEINS; ZEALAND BLACK MICE; CD5 B-CELLS; MOUSE PLASMACYTOMAS; TRANSGENIC MICE C1 KAROLINSKA INST,DEPT TUMOR BIOL,S-10401 STOCKHOLM 60,SWEDEN. RP POTTER, M (reprint author), NCI,DCBDC,BETHESDA,MD 20892, USA. NR 155 TC 151 Z9 153 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 OCT PY 1992 VL 13 IS 10 BP 1681 EP 1697 DI 10.1093/carcin/13.10.1681 PG 17 WC Oncology SC Oncology GA JU195 UT WOS:A1992JU19500001 PM 1423827 ER PT J AU ZHU, SY GRAY, TE NETTESHEIM, P AF ZHU, SY GRAY, TE NETTESHEIM, P TI THE EFFECT OF SODIUM SELENITE ON CELL-PROLIFERATION AND TRANSFORMATION OF PRIMARY RAT TRACHEAL EPITHELIAL-CELLS SO CARCINOGENESIS LA English DT Article ID SERUM-FREE MEDIUM; DIETARY SELENIUM; MAMMARY CELLS; NEOPLASTIC PROGRESSION; CLONAL PROLIFERATION; CANCER MORTALITY; GROWTH-FACTORS; INHIBITION; INVITRO; CARCINOGENESIS AB The effects of sodium selenite (Na2SeO3) on cell proliferation and the development of preneoplastic transformed variants were studied in primary cultures of rat tracheal epithelial cells. Results revealed a biphasic effect of Na2SeO3 on cell proliferation: at concentrations between 6 x 10(-8) and 6 x 10(-6) M, it stimulated and at concentrations of approximately 2 x 10(-5) and above it inhibited cell proliferation (presumably due to toxicity). Nontoxic concentrations of Na2SeO3 (6 x 10(-8)-6 x 10(-7) M) significantly reduced the spontaneous transformation frequency. Transformation induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was effectively inhibited by nontoxic as well as toxic concentrations of Na2SeO3. Treatment of cultures with Na2SeO3 after cessation of NNK exposure, i.e. during the selection period, also significantly reduced the transformation frequency. These experiments show that the inhibition of transformation by Na2SeO3 is not the result of an antiproliferative effect. They further indicate that the inhibitory effect occurs even when the chemical treatment occurs during the `postinitiation' phase. Thus the inhibition of transformation by Na2SeO3 cannot solely be explained by its effects on drug metabolism. C1 NIEHS,PULM PATHOBIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 37 TC 20 Z9 21 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 OCT PY 1992 VL 13 IS 10 BP 1725 EP 1729 DI 10.1093/carcin/13.10.1725 PG 5 WC Oncology SC Oncology GA JU195 UT WOS:A1992JU19500006 PM 1330341 ER PT J AU DIWAN, BA LUBET, RA WARD, JM HRABIE, JA RICE, JM AF DIWAN, BA LUBET, RA WARD, JM HRABIE, JA RICE, JM TI TUMOR-PROMOTING AND HEPATOCARCINOGENIC EFFECTS OF 1,4-BIS[2-(3,5-DICHLOROPYRIDYLOXY)]BENZENE (TCPOBOP) IN DBA/2NCR AND 2C57BL/6NCR MICE AND AN APPARENT PROMOTING EFFECT ON NASAL CAVITY TUMORS BUT NOT ON HEPATOCELLULAR TUMORS IN F344/NCR RATS INITIATED WITH N-NITROSODIETHYLAMINE SO CARCINOGENESIS LA English DT Article ID PHENOBARBITAL-LIKE INDUCER; MONO-OXYGENASE ACTIVITY; NUCLEAR-DNA; LIVER; INDUCTION; 8-HYDROXYDEOXYGUANOSINE; DIETHYLNITROSAMINE; SUSCEPTIBILITY; EXPOSURE AB The tumor-promoting and carcinogenic effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) in the liver and in other organs were quantified and compared to those of phenobarbital (PB) in two inbred strains of mice (C57BL/6NCr, DBA/2NCr) and in F344/NCr rats initiated at 5 weeks of age with N-nitrosodiethylamine (NDEA; 90 mg/kg in mice, 75 mg/kg in rats). Two weeks later animals were placed on a regimen of TCPOBOP once every 2 weeks (administered i.p. or i.g.) or on a diet containing 500 p.p.m. PB as a positive control for the duration of the experiment. Mice were administered TCPOBOP (3.0 mg/kg/dose) for 30 weeks followed by control diet, while rats were given the TCPOBOP regimen (3.0 or 30 mg/kg/dose) for the full 78 weeks of the experiment. TCPOBOP was a complete carcinogen and an extremely potent promoter in both strains of mice, particularly the DBA strain in which NDEA followed by TCPOBOP (i.p.) resulted in death of all the animals within 30 weeks from multiple hepatocellular tumors. TCPOBOP alone induced 100% tumor incidence in DBA mice within 60 weeks. In addition, in both strains of mice, a high proportion of those animals with liver tumors had metastases to the lungs. In contrast, TCPOBOP was ineffective as a liver tumor promoter in F344 rats at even 10 times the dose administered to mice. Interestingly however, TCPOBOP, when given subsequent to NDEA, caused a significant increase in nasal cavity tumors in F344 rats. PB was an effective liver tumor promoter in male DBA mice and male F344 rats, but was relatively ineffective as a promoter in C57 mice. When tumor-promoting activity and induction of cytochrome P450 IIB1 were compared, good agreement between these two parameters was observed. PB was an effective inducer of P450 IIB1 in the rats and in both strains of mice and a potent liver tumor promoter in both DBA mice and F344 rats, whereas TCPOBOP was a potent inducer and tumor promoter in both strains of mice but was negligibly effective as either an inducer or a promoter in F344 rats at even 10-fold higher dosage. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. PROGRAM RESOURCES INC DYNCORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. RP DIWAN, BA (reprint author), PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 37 TC 39 Z9 40 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 OCT PY 1992 VL 13 IS 10 BP 1893 EP 1901 DI 10.1093/carcin/13.10.1893 PG 9 WC Oncology SC Oncology GA JU195 UT WOS:A1992JU19500033 PM 1330346 ER PT J AU WATSON, DK SMYTH, FE THOMPSON, DM CHENG, JQ TESTA, JR PAPAS, TS SETH, A AF WATSON, DK SMYTH, FE THOMPSON, DM CHENG, JQ TESTA, JR PAPAS, TS SETH, A TI THE ERGB FLI-1 GENE - ISOLATION AND CHARACTERIZATION OF A NEW MEMBER OF THE FAMILY OF HUMAN ETS TRANSCRIPTION FACTORS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MURINE LEUKEMIA-VIRUS; VIRAL INTEGRATION REGION; LONG TERMINAL REPEAT; DNA-BINDING; T-CELL; C-ETS-1 PROTOONCOGENE; SARCOMA-VIRUS; SEQUENCE; ONCOGENE; IDENTIFICATION AB All cellular ets proteins contain a region of high amino acid identity to those found in the last two exons of the ets-1 gene (C domain). We have identified and characterized a new member of the human ETS gene family, ERGB. The ERGB gene shows extensive amino acid identity to the human ERG and the mouse Fli-1 genes. The ERGB gene is found to be transcriptionally active in a variety of human cell lines and tissues, in contrast to the more restrictive expression pattern of the ERG gene. The ERGB gene encodes for a 3.2-kilobase mRNA containing an open reading frame of 451 amino acids. The ERGB gene, like human ETS1, is located on chromosome 11 and is transposed to chromosome 4 as a result of the translocation t(4;11) associated with leukemia. Pulse-field gel analysis suggests that ETS1 and ERGB are more than 200 kilobases apart. Similar to the other members of the ets family (ets1, ets2), this new member is also able to trans-activate transcription of a reporter gene linked to the ETS-binding sequences derived from either the GATA-1 promoter or an optimal Ets-binding site. C1 PROGRAM RESOURCES INC,FREDERICK,MD 21702. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. RP WATSON, DK (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. NR 43 TC 106 Z9 109 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 OCT PY 1992 VL 3 IS 10 BP 705 EP 713 PG 9 WC Cell Biology SC Cell Biology GA JT391 UT WOS:A1992JT39100006 PM 1445800 ER PT J AU ALEXANDROPOULOS, K QURESHI, SA BRUDER, JT RAPP, U FOSTER, DA AF ALEXANDROPOULOS, K QURESHI, SA BRUDER, JT RAPP, U FOSTER, DA TI THE INDUCTION OF ERG-1 EXPRESSION BY V-FPS IS VIA A PROTEIN-KINASE C-INDEPENDENT INTRACELLULAR SIGNAL THAT IS SEQUENTIALLY DEPENDENT UPON HARAS AND RAF-1 SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID FUJINAMI SARCOMA-VIRUS; GTPASE-ACTIVATING PROTEIN; TYROSINE KINASES; BIOLOGICAL-ACTIVITY; PLATELET PROTEIN; GENE-EXPRESSION; EGR FAMILY; 3T3 CELLS; TRANSFORMATION; GROWTH AB Activating the protein-tyrosine kinase activity of v-Fps leads to the rapid transcriptional activation of the Egr-1 gene, which encodes a mitogen-responsive transcription factor. Activation of Egr-1 by v-Fps was insensitive to protein kinase C depletion, suggesting that a protein kinase C-independent signal activated by v-Fps leads to the induction of Egr-1. Expression of v-Fps in transient expression assays induced Egr-1 promoter activation. v-HaRas and v-Raf also activated the Egr-1 promoter. To characterize HaRas and Raf-1 involvement in v-Fps-induced Egr-1 expression, we used recently characterized dominant negative mutants of HaRas and Raf-1. v-Fps-induced Egr-1 promoter activation was inhibited by the dominant negative mutants of both HaRas and Raf-1. v-HaRas-induced Egr-1 promoter activation was blocked by the negative Raf-1 mutant, however, v-Raf-1-induced Egr-1 promoter activation was unaffected by the inhibitory HaRas mutant. These data suggest that v-Fps activates a protein kinase C-independent intracellular signaling pathway that is dependent on both HaRas and Raf-1, where Raf-1 functions downstream of HaRas. C1 CUNY HUNTER COLL,DEPT BIOL SCI,INST BIOMOLEC STRUCT & FUNCT,695 PK AVE,NEW YORK,NY 10021. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. FU NCI NIH HHS [CA46677]; NCRR NIH HHS [RRO-3037-03] NR 49 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1992 VL 3 IS 10 BP 731 EP 737 PG 7 WC Cell Biology SC Cell Biology GA JT391 UT WOS:A1992JT39100009 PM 1332742 ER PT J AU BEEBE, LE FORNWALD, LW ANDERSON, LM AF BEEBE, LE FORNWALD, LW ANDERSON, LM TI EFFECT OF A SINGLE ORAL DOSE OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON HEPATIC AND EXTRAHEPATIC CYTOCHROME-P-450 IA INDUCTION IN THE SWISS MOUSE SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 11TH INTERNATIONAL SYMP ON CHLORINATED DIOXINS AND RELATED COMPOUNDS CY SEP 23-27, 1991 CL RESEARCH TRIANGLE PK, NC ID LIVER AB The cytochrome P-450 1A1 induction response following TCDD exposure has been characterized in liver; however little is known regarding extrahepatic targets of TCDD. This study was designed to compare the 1A1 induction response of hepatic to extrahepatic tissue after oral TCDD exposure. 1A1 was induced in all tissues, with liver, lung and kidney exhibiting an early maximum and subsequent gradual decrease over 4 weeks, and intestines demonstrating a rapid loss of enzyme activity over time. The magnitude of induction was significantly greater in liver and lung following oral vs. intraperitoneal administration. These studies suggest differences in 1A1 induction in hepatic vs. extrahepatic tissue and with different routes of administration. C1 NCI,FCRDC,PROGRAM RESOURCES INC DYNCORP,BCDP,FREDERICK,MD 21702. RP BEEBE, LE (reprint author), NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701, USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD OCT-NOV PY 1992 VL 25 IS 7-10 BP 1141 EP 1145 DI 10.1016/0045-6535(92)90120-G PG 5 WC Environmental Sciences SC Environmental Sciences & Ecology GA KC160 UT WOS:A1992KC16000039 ER PT J AU DIODATI, JG CANNON, RO QUYYUMI, AA AF DIODATI, JG CANNON, RO QUYYUMI, AA TI PLATELET ACTIVATION IN CORONARY-ARTERY DISEASE - INDUCTION BY PHYSICAL AND MENTAL STRESS, AND ATTENUATION BY NITROGLYCERIN, NITROPRUSSIDE AND ASPIRIN SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 16 EP 16 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000095 ER PT J AU DILISA, F SILVERMAN, HS STERN, MD BLANK, PS GAMBASSI, G HANSFORD, RG AF DILISA, F SILVERMAN, HS STERN, MD BLANK, PS GAMBASSI, G HANSFORD, RG TI EFFECTS OF ANOXIA AND REOXYGENATION ON MITOCHONDRIAL-MEMBRANE POTENTIAL OF SINGLE CARDIAC MYOCYTES SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,GERIATR RES CTR,BALTIMORE,MD 21224. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 35 EP 35 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000167 ER PT J AU SILVERMAN, HS DILISA, F HUI, RC MIYATA, H BLANK, PS HANSFORD, RG LAKATTA, EG STERN, MD AF SILVERMAN, HS DILISA, F HUI, RC MIYATA, H BLANK, PS HANSFORD, RG LAKATTA, EG STERN, MD TI REVERSIBLE RISES IN INTRACELLULAR FREE MAGNESIUM REFLECT DYNAMIC CHANGES IN INTRACELLULAR ATP IN HYPOXIC SINGLE CARDIAC MYOCYTES SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,GERIATR RES CTR,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 35 EP 35 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000169 ER PT J AU IKEWAKI, K RADER, DJ NISHIWAKI, M SAKAMOTO, T SCHAEFER, JR THOMAS, F ZECH, LA ISHIKAWA, T NAGANO, M NAKAMURA, H BREWER, HB AF IKEWAKI, K RADER, DJ NISHIWAKI, M SAKAMOTO, T SCHAEFER, JR THOMAS, F ZECH, LA ISHIKAWA, T NAGANO, M NAKAMURA, H BREWER, HB TI CHOLESTEROL ESTER TRANSFER PROTEIN-DEFICIENCY - INVIVO METABOLISM OF APOE AND APO-B SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 71 EP 71 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000313 ER PT J AU DUVERGER, NJ RADER, DJ DUCHATEAU, P AILHAUD, G FRUCHART, JC CASTRO, G BREWER, HB AF DUVERGER, NJ RADER, DJ DUCHATEAU, P AILHAUD, G FRUCHART, JC CASTRO, G BREWER, HB TI COMPOSITION AND METABOLIC-ACTIVITY OF SUBPOPULATIONS OF LIPOPROTEIN PARTICLES CONTAINING APOA-I WITHOUT APOA-II (LPA-I) FROM NORMOLIPIDEMIC HUMAN-SUBJECTS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 73 EP 73 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000319 ER PT J AU VERGES, B RADER, DJ SCHAFER, JR LOHSE, P ZECH, LA GAMBERT, P STEINMETZ, A BREWER, HB AF VERGES, B RADER, DJ SCHAFER, JR LOHSE, P ZECH, LA GAMBERT, P STEINMETZ, A BREWER, HB TI INVIVO CATABOLISM OF APOA-IV-ISOPROTEINS APOA-IV-1 AND APOA-IV-2 IN NORMAL AND HYPERTRIGLYCERIDEMIC SUBJECTS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 73 EP 73 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000318 ER PT J AU ARRIGHI, JA DIODATI, JG BACHARACH, SL UDDIN, S BONOW, RO DILSIZIAN, V AF ARRIGHI, JA DIODATI, JG BACHARACH, SL UDDIN, S BONOW, RO DILSIZIAN, V TI THE DETECTION OF VIABLE MYOCARDIUM BY TC-99M SESTAMIBI IS ENHANCED WHEN THE SEVERITY OF IRREVERSIBLE DEFECTS ARE ASSESSED SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 108 EP 108 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000458 ER PT J AU YUSUF, S GARCES, C PEPINE, CJ AF YUSUF, S GARCES, C PEPINE, CJ TI PROGNOSTIC IMPORTANCE OF INFARCTION AND UNSTABLE ANGINA IN PATIENTS WITH LEFT-VENTRICULAR DYSFUNCTION SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 135 EP 135 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000566 ER PT J AU LEE, SW KAHN, ML DICHEK, DA AF LEE, SW KAHN, ML DICHEK, DA TI DIRECT ATTACHMENT OF UROKINASE TO THE ENDOTHELIAL-CELL SURFACE CONFERS RESISTANCE TO PLASMINOGEN-ACTIVATOR INHIBITOR-1 INHIBITION INVITRO SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 149 EP 149 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000621 ER PT J AU ZIEGELSTEIN, RC PILI, R PASSANITI, A ZWEIER, JL LEFER, D CAPOGROSSI, MC AF ZIEGELSTEIN, RC PILI, R PASSANITI, A ZWEIER, JL LEFER, D CAPOGROSSI, MC TI LEUKOCYTE ADHESION TO HUMAN OR BOVINE AORTIC ENDOTHELIUM INCREASES ENDOTHELIAL-CELL CALCIUM SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NIA,BIOL CHEM LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 161 EP 161 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000668 ER PT J AU ZIEGELSTEIN, RC CHENG, L AVERSANO, T OUYANG, P STERN, MD SILVERMAN, HS AF ZIEGELSTEIN, RC CHENG, L AVERSANO, T OUYANG, P STERN, MD SILVERMAN, HS TI ALTERED ENERGY-METABOLISM AFFECTS INTRACELLULAR CALCIUM IN CULTURED AORTIC ENDOTHELIAL-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 161 EP 161 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000669 ER PT J AU KAMP, TJ MITAS, M MARBAN, E NIRENBERG, M AF KAMP, TJ MITAS, M MARBAN, E NIRENBERG, M TI ENHANCER REGION CONTAINING (GAT)7 REGULATES EXPRESSION OF A NEURONAL CALCIUM-CHANNEL GENE SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 176 EP 176 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000728 ER PT J AU SAVAGE, PJ SHOLINSKY, P FLACK, JM LIU, K AF SAVAGE, PJ SHOLINSKY, P FLACK, JM LIU, K TI TRACKING OF CVD RISK FACTOR CLUSTERS IN YOUNG-ADULTS - THE CARDIA STUDY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 198 EP 198 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000816 ER PT J AU PATTERSON, AP EGGERMAN, TL RUBIN, DC GORDON, JI BREWER, HB AF PATTERSON, AP EGGERMAN, TL RUBIN, DC GORDON, JI BREWER, HB TI APO-B MESSENGER-RNA EDITING DEVELOPS NORMALLY EXSITU SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. WASHINGTON UNIV,ST LOUIS,MO 63130. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 207 EP 207 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000847 ER PT J AU MURPHY, E LONDON, RE STEENBERGEN, C AF MURPHY, E LONDON, RE STEENBERGEN, C TI SOME ADENOSINE ANTAGONIST BLOCK GLUCOSE-UPTAKE SO CIRCULATION LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. DUKE UNIV,DEPT PATHOL,DURHAM,NC 27706. NR 0 TC 2 Z9 2 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 OCT PY 1992 VL 86 IS 4 SU S BP 214 EP 214 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000875 ER PT J AU GAMBASSI, G SPURGEON, HA CAPOGROSSI, MC AF GAMBASSI, G SPURGEON, HA CAPOGROSSI, MC TI DIFFERENT EFFECTS OF ALPHA-1-ADRENERGIC RECEPTOR SUBTYPES ON AFTERCONTRACTIONS DURING RECOVERY FROM ACIDOSIS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,LCS,BALTIMORE,MD 21224. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 217 EP 217 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000885 ER PT J AU MORLEY, D MARAGOS, C ZHANG, XY KEEFER, L AF MORLEY, D MARAGOS, C ZHANG, XY KEEFER, L TI DURATION OF BIOLOGIC ACTION OF NITRIC-OXIDE NUCLEOPHILE VASODILATOR COMPOUNDS CAN BE VARIED BY ALTERATION OF THE CARRIER NUCLEOPHILE SO CIRCULATION LA English DT Meeting Abstract C1 TEMPLE UNIV,HLTH SCI CTR,SCH MED,PHILADELPHIA,PA 19140. NCI,FCRDC,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 223 EP 223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000910 ER PT J AU ZIEGELSTEIN, RC CHENG, L HELDMAN, AW CAPOGROSSI, MC AF ZIEGELSTEIN, RC CHENG, L HELDMAN, AW CAPOGROSSI, MC TI FLOW-INDUCED MODULATION OF ENDOTHELIAL-CELL PH SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. RI Heldman, Alan/K-8784-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 223 EP 223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000911 ER PT J AU GILLIGAN, DM PANZA, JA KILCOYNE, CM DIODATI, JG CASINO, PR QUYYUMI, AA AF GILLIGAN, DM PANZA, JA KILCOYNE, CM DIODATI, JG CASINO, PR QUYYUMI, AA TI THE CONTRIBUTION OF ENDOTHELIUM-DERIVED NITRIC-OXIDE TO EXERCISE-INDUCED VASODILATION IN MAN SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 224 EP 224 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000915 ER PT J AU FANANAPAZIR, L EPSTEIN, N AF FANANAPAZIR, L EPSTEIN, N TI GENOTYPE-PHENOTYPE STUDIES IN HYPERTROPHIC CARDIOMYOPATHY - INSIGHTS PROVIDED BY COMPARISONS OF KINDREDS WITH IDENTICAL BETA-MYOSIN HEAVY-CHAIN GENE-MUTATIONS SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 228 EP 228 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000931 ER PT J AU CUDA, G FANANAPAZIR, L EPSTEIN, N SELLERS, J AF CUDA, G FANANAPAZIR, L EPSTEIN, N SELLERS, J TI ABNORMAL MYOSIN INVITRO MOTILITY ACTIVITY IN 2 HYPERTROPHIC CARDIOMYOPATHY KINDREDS WITH DISTINCT CARDIAC BETA-MYOSIN HEAVY-CHAIN GENE-MUTATIONS SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 229 EP 229 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000934 ER PT J AU EPSTEIN, N ZHU, WS CUDA, G SELLERS, J CYRAN, F COHN, G FANANAPAZIR, L AF EPSTEIN, N ZHU, WS CUDA, G SELLERS, J CYRAN, F COHN, G FANANAPAZIR, L TI MUTANT MESSAGE AND MYOSIN PROTEIN IN SKELETAL-MUSCLE OF HYPERTROPHIC CARDIOMYOPATHY PATIENTS WITH DISTINCT MUTATIONS IN THE BETA-MYOSIN HEAVY-CHAIN GENE SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 229 EP 229 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000933 ER PT J AU FANANAPAZIR, L DALAKAS, M CYRAN, F COHN, G EPSTEIN, N AF FANANAPAZIR, L DALAKAS, M CYRAN, F COHN, G EPSTEIN, N TI CENTRAL CORE DISEASE IS PRESENT IN HYPERTROPHIC CARDIOMYOPATHY PATIENTS WITH DISTINCT MUTATIONS IN THE BETA-MYOSIN HEAVY-CHAIN GENE SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 229 EP 229 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000936 ER PT J AU FANANAPAZIR, L BONOW, RO DILSIZIAN, V AF FANANAPAZIR, L BONOW, RO DILSIZIAN, V TI DUAL CHAMBER PACING RELIEVES ANGINA AND IMPROVES MYOCARDIAL PERFUSION ABNORMALITIES IN PATIENTS WITH OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 273 EP 273 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001111 ER PT J AU MCAREAVEY, D TRIPODI, D FANANAPAZIR, L AF MCAREAVEY, D TRIPODI, D FANANAPAZIR, L TI DUAL CHAMBER PACING CAUSES PROGRESSIVE RELIEF OF LEFT-VENTRICULAR OUTFLOW OBSTRUCTION IN HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 273 EP 273 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001109 ER PT J AU SORKIN, JD KATZEL, LI BUSBY, MJ LAKATTA, L FLEG, JL AF SORKIN, JD KATZEL, LI BUSBY, MJ LAKATTA, L FLEG, JL TI METABOLIC RISK-FACTORS FOR EXERCISE INDUCED SILENT-MYOCARDIAL-ISCHEMIA IN APPARENTLY HEALTHY-MEN SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,NIA,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 325 EP 325 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001319 ER PT J AU SHRIVASTAV, S SMALE, G SASSE, J BIRO, S LAPPI, DA CASSCELLS, W AF SHRIVASTAV, S SMALE, G SASSE, J BIRO, S LAPPI, DA CASSCELLS, W TI INDUCTION OF BASIC FGF AND FGF RECEPTOR-1 BY EXPOSURE OF SMOOTH-MUSCLE CELLS TO SERUM SO CIRCULATION LA English DT Meeting Abstract C1 SCRIPPS CLIN & HOSP,WHITTIER INST DIABET & ENDOCRINOL,LA JOLLA,CA 92037. SHRINERS HOSP CRIPPLED CHILDREN,TAMPA,FL. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 334 EP 334 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001356 ER PT J AU LESNIK, P ROUIS, M SKARLATOS, S KRUTH, HS CHAPMAN, MJ AF LESNIK, P ROUIS, M SKARLATOS, S KRUTH, HS CHAPMAN, MJ TI CELLULAR CHOLESTEROL CONTENT REGULATES EXPRESSION OF TISSUE FACTOR (TF) BY HUMAN MONOCYTE-DERIVED MACROPHAGES (MDM) SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. INSERM,U321,F-75005 PARIS,FRANCE. RI Rouis, Mustapha/E-4993-2016; Lesnik, Philippe/F-7803-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 335 EP 335 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001358 ER PT J AU STEENBERGEN, C LONDON, RE MURPHY, E AF STEENBERGEN, C LONDON, RE MURPHY, E TI MECHANISMS OF PRECONDITIONING IN INVITRO RAT HEARTS SO CIRCULATION LA English DT Meeting Abstract C1 DUKE UNIV,DEPT PATHOL,DURHAM,NC 27706. NIEHS,LMB,RES TRIANGLE PK,NC 27709. NR 0 TC 2 Z9 2 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 OCT PY 1992 VL 86 IS 4 SU S BP 341 EP 341 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001382 ER PT J AU ZHU, WS FANANAPAZIR, L EPSTEIN, N AF ZHU, WS FANANAPAZIR, L EPSTEIN, N TI IDENTIFICATION OF PUTATIVE TRANSLATIONAL CONTROL ELEMENTS IN NEW 5' UNTRANSLATED REGION IN THE BETA-MYOSIN HEAVY-CHAIN GENE MESSAGE SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 351 EP 351 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001422 ER PT J AU SCHUCKER, B DERBY, B WITTES, JT LEVY, A SANTANELLO, NC DONATO, K AF SCHUCKER, B DERBY, B WITTES, JT LEVY, A SANTANELLO, NC DONATO, K TI THE IMPACT OF NATIONAL CHOLESTEROL EDUCATIONAL EFFORTS ON BLACK-AND-WHITE ADULT AMERICANS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 402 EP 402 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001624 ER PT J AU KLEIN, HG DUVERGER, N ALBERS, JJ BREWER, HB SANTAMARINAFOJO, S AF KLEIN, HG DUVERGER, N ALBERS, JJ BREWER, HB SANTAMARINAFOJO, S TI LECITHIN-CHOLESTEROL ACYLTRANSFERASE DEFICIENCY - INVITRO EXPRESSION OF GENE DEFECTS ASSOCIATED WITH CLASSIC LCAT DEFICIENCY AND FISH EYE DISEASE SO CIRCULATION LA English DT Meeting Abstract C1 UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,MDB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 420 EP 420 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001695 ER PT J AU HOLLENBERG, SM SHELHAMER, JH TONG, W CUNNION, RE AF HOLLENBERG, SM SHELHAMER, JH TONG, W CUNNION, RE TI ENDOTHELIN-1 PRODUCTION BY HUMAN AORTIC ENDOTHELIAL-CELLS AFTER EICOSANOID STIMULATION SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 430 EP 430 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001737 ER PT J AU KLUES, HG DOLLAR, AL PROSCHAN, MM SPIRITO, P ROBERTS, WC MARON, BJ AF KLUES, HG DOLLAR, AL PROSCHAN, MM SPIRITO, P ROBERTS, WC MARON, BJ TI PREDICTION OF MITRAL-VALVE SIZE AND DIMENSIONS IN HYPERTROPHIC CARDIOMYOPATHY BY ECHOCARDIOGRAPHY - VALIDATION FROM MITRAL-VALVE SPECIMENS IN THE SAME PATIENTS SO CIRCULATION LA English DT Meeting Abstract C1 RHEIN WESTFAL TH AACHEN,MED CLIN 1,W-5100 AACHEN,GERMANY. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 447 EP 447 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001803 ER PT J AU CHANG, AC BARTLETT, T MCAREAVEY, D TRIPODI, D FANANAPAZIR, L AF CHANG, AC BARTLETT, T MCAREAVEY, D TRIPODI, D FANANAPAZIR, L TI ATRIOVENTRICULAR NODE ABLATION COUPLED WITH RATE-RESPONSIVE VENTRICULAR DEMAND PACING IMPROVES SYMPTOMS AND HEMODYNAMICS IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY AND DRUG-REFRACTORY ATRIAL-FIBRILLATION SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 451 EP 451 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001817 ER PT J AU GAMBASSI, G SPURGEON, HA CAPOGROSSI, MC AF GAMBASSI, G SPURGEON, HA CAPOGROSSI, MC TI REBOUND ENHANCEMENT OF MYOFILAMENT SENSITIVITY TO CA2+ FOLLOWING HYPERCARBIC ACIDOSIS IN CARDIAC-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,LCS,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 479 EP 479 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001926 ER PT J AU DIODATI, JG CANNON, RO GILLIGAN, DM PANZA, JA DAKAK, N QUYYUMI, AA AF DIODATI, JG CANNON, RO GILLIGAN, DM PANZA, JA DAKAK, N QUYYUMI, AA TI INHIBITION OF PLATELET-AGGREGATION BY ENDOTHELIUM-DERIVED RELAXING FACTOR - REDUCED RESPONSE IN ATHEROSCLEROSIS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 490 EP 490 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66001970 ER PT J AU CHEW, PH TALAN, MI BUSH, DE ABELL, RT PETRLIK, J ENGEL, BT AF CHEW, PH TALAN, MI BUSH, DE ABELL, RT PETRLIK, J ENGEL, BT TI BE STILL MY HEART - OVERNIGHT HEART-RATE AND FUNCTION SO CIRCULATION LA English DT Meeting Abstract C1 FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD. NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 528 EP 528 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002120 ER PT J AU TEO, K YUSUF, S FURBERG, C AF TEO, K YUSUF, S FURBERG, C TI OVERVIEW OF RANDOMIZED TRIALS OF LOW-DOSE AMIODARONE ON MORTALITY IN CARDIAC PATIENTS SO CIRCULATION LA English DT Meeting Abstract C1 UNIV ALBERTA,EDMONTON T6G 2E1,ALBERTA,CANADA. NHLBI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 534 EP 534 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002145 ER PT J AU REMALEY, AT WONG, A SCHUMACHER, UK MENG, MS BREWER, HB HOEG, JM AF REMALEY, AT WONG, A SCHUMACHER, UK MENG, MS BREWER, HB HOEG, JM TI MODULATION OF APOA-II BINDING TO HDL BY GLYCOSYLATION SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 552 EP 552 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002215 ER PT J AU CANNON, RO QUYYUMI, AA DILSIZIAN, V AF CANNON, RO QUYYUMI, AA DILSIZIAN, V TI ASSOCIATION OF ABNORMAL LEFT-VENTRICULAR RESPONSE TO EXERCISE WITH DYNAMIC LIMITATION IN CORONARY FLOW RESERVE IN PATIENTS WITH CHEST PAIN, ANGIOGRAPHICALLY NORMAL CORONARY-ARTERIES SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 588 EP 588 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002361 ER PT J AU MARON, BJ MCINTOSH, CL KLUES, HG CANNON, RO ROBERTS, WC AF MARON, BJ MCINTOSH, CL KLUES, HG CANNON, RO ROBERTS, WC TI MORPHOLOGIC BASIS FOR OBSTRUCTION TO RIGHT VENTRICULAR OUTFLOW IN HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 592 EP 592 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002377 ER PT J AU MANOLIO, TA FURBERG, CD RAUTAHARJU, PM SISCOVICK, D NEWMAN, AB BORHANI, NO GARDIN, JM AF MANOLIO, TA FURBERG, CD RAUTAHARJU, PM SISCOVICK, D NEWMAN, AB BORHANI, NO GARDIN, JM TI VENTRICULAR-TACHYCARDIA ON 24-HOUR AMBULATORY ELECTROCARDIOGRAPHY IN THE ELDERLY - THE CARDIOVASCULAR HEALTH STUDY (CHS) SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,CHS COLLABORAT RES GRP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 598 EP 598 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002400 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 LIPOPROTEIN AND HEPATIC LIPASE LOOP STRUCTURE - ESSENTIAL ROLE OF AMPHIPATHIC HELICES FOR LIPASE SUBSTRATE INTERACTION SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 607 EP 607 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002435 ER PT J AU PREVIATO, L GUARDAMAGNA, O BRUNZELL, JD SANTAMARINAFOJO, S BREWER, HB AF PREVIATO, L GUARDAMAGNA, O BRUNZELL, JD SANTAMARINAFOJO, S BREWER, HB TI A NOVEL MISSENSE MUTATION IN THE C-TERMINAL DOMAIN OF LIPOPROTEIN-LIPASE LEADS TO ENZYME INACTIVATION SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIV TURIN,DEPT PEDIAT,I-10124 TURIN,ITALY. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 608 EP 608 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002437 ER PT J AU CASINO, PR KILCOYNE, CM QUYYUMI, AA HOEG, JM EPSTEIN, SE PANZA, JA AF CASINO, PR KILCOYNE, CM QUYYUMI, AA HOEG, JM EPSTEIN, SE PANZA, JA TI ROLE OF NITRIC-OXIDE IN THE ENDOTHELIUM-DEPENDENT VASODILATION OF HYPERCHOLESTEROLEMIC PATIENTS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 618 EP 618 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002478 ER PT J AU GAMBASSI, G CAPOGROSSI, MC AF GAMBASSI, G CAPOGROSSI, MC TI PROTEIN KINASE-C-DEPENDENCE OF ALPHA(1)-ADRENERGIC EFFECTS ON CYTOSOLIC PH AND CONTRACTION IN CARDIAC MYOCYTES SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 621 EP 621 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002490 ER PT J AU XIAO, RP SPURGEON, HA LAKATTA, EG AF XIAO, RP SPURGEON, HA LAKATTA, EG TI OPIOID PEPTIDE MODULATION OF ADRENERGIC EFFECTS ON CARDIAC-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 622 EP 622 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002493 ER PT J AU GAMBASSI, G SOLARO, JR SPURGEON, HA LAKATTA, EG AF GAMBASSI, G SOLARO, JR SPURGEON, HA LAKATTA, EG TI EMD-57033, A NOVEL INOTROPIC AGENT, REVERSES MYOFILAMENT EFFECTS OF BUTANEDIONE MONOXIME (BDM) SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 623 EP 623 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002498 ER PT J AU SMITH, CJ KRALL, J MANGANIELLO, VC MOVSESIAN, MA AF SMITH, CJ KRALL, J MANGANIELLO, VC MOVSESIAN, MA TI SARCOPLASMIC RETICULUM-ASSOCIATED CGMP-INHIBITED, CAMP PHOSPHODIESTERASE ACTIVITY IN RODENT, RABBIT, CANINE AND HUMAN MYOCARDIUM SO CIRCULATION LA English DT Meeting Abstract C1 NEW YORK MED COLL,VALHALLA,NY 10595. NHLBI,BETHESDA,MD 20892. UNIV UTAH,SALT LAKE CITY,UT 84112. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 623 EP 623 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002496 ER PT J AU MAYUGA, R FLEG, JL ARRINGTON, CT OCONNOR, FC AF MAYUGA, R FLEG, JL ARRINGTON, CT OCONNOR, FC TI ROLE OF LEFT-VENTRICULAR ANATOMY IN EXERCISE-INDUCED VENTRICULAR ARRHYTHMIAS IN HEALTHY-VOLUNTEERS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 669 EP 669 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002681 ER PT J AU PELLICCIA, A MARON, BJ SPATARO, A CASELLI, G GRANATA, M AF PELLICCIA, A MARON, BJ SPATARO, A CASELLI, G GRANATA, M TI EFFECTS OF INTENSE POWER TRAINING ON CARDIAC DIMENSIONS - RELEVANCY TO DIFFERENTIAL-DIAGNOSIS OF HYPERTROPHIC CARDIOMYOPATHY AND ATHLETE HEART SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. INST SPORTS SCI,ROME,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 669 EP 669 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002680 ER PT J AU KATZEL, LI LAKATTA, L SCHULMAN, SP DRINKWATER, DT BECKER, LC MULLER, D FLEG, JL AF KATZEL, LI LAKATTA, L SCHULMAN, SP DRINKWATER, DT BECKER, LC MULLER, D FLEG, JL TI DOES REGULAR VIGOROUS EXERCISE PROTECT AGAINST OCCULT CORONARY-ARTERY DISEASE IN OLDER MEN SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MARYLAND,COLL PK,MD 20742. VET ADM MED CTR,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 672 EP 672 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002693 ER PT J AU CZAJKOWSKI, SM LINDQUIST, R HOOGWERF, B DUPULS, G SHUMAKER, SA TERRIN, ML KNATTERUD, GL AF CZAJKOWSKI, SM LINDQUIST, R HOOGWERF, B DUPULS, G SHUMAKER, SA TERRIN, ML KNATTERUD, GL TI WOMEN CORONARY-ARTERY BYPASS GRAFT (CABG) SURGERY PATIENTS ARE SICKER AND HAVE FEWER SOCIAL AND ECONOMIC-RESOURCES THAN MEN SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 674 EP 674 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002702 ER PT J AU KAHN, ML LEE, SW DICHEK, DA AF KAHN, ML LEE, SW DICHEK, DA TI PLASMINOGEN-ACTIVATOR INHIBITOR-1 (PAI-1) EXPRESSION IS RESISTANT TO INHIBITION BY ANTISENSE RETROVIRAL VECTORS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 737 EP 737 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002954 ER PT J AU SOLLOTT, SJ LAKATTA, E AF SOLLOTT, SJ LAKATTA, E TI SECONDARY [CA2+]I-DEPENDENT MODULATION OF CONTRACTILITY IN SINGLE CARDIAC MYOCYTES SO CIRCULATION LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. NR 0 TC 6 Z9 6 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 749 EP 749 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66002999 ER PT J AU JANCZEWSKI, AM SOLLOTT, SJ SPURGEON, HA LAKATTA, EG AF JANCZEWSKI, AM SOLLOTT, SJ SPURGEON, HA LAKATTA, EG TI MITOCHONDRIAL FREE CA2+ IN SINGLE VENTRICULAR MYOCYTES RAPIDLY RESPONDS TO CHANGES IN CYTOSOLIC [CA2+] SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 750 EP 750 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003001 ER PT J AU ZIEGELSTEIN, RC PILI, R PASSANITI, A CHENG, L SPURGEON, HA CAPOGROSSI, MC AF ZIEGELSTEIN, RC PILI, R PASSANITI, A CHENG, L SPURGEON, HA CAPOGROSSI, MC TI A RYANODINE SENSITIVE INTRACELLULAR CA2+ STORE IS PRESENT IN ENDOTHELIAL-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NIA,BIOL CHEM LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DIV CARDIOL,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 750 EP 750 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003002 ER PT J AU BRADY, AJ POOLEWILSON, PA HARDING, SE WARREN, JB AF BRADY, AJ POOLEWILSON, PA HARDING, SE WARREN, JB TI INHIBITION OF NITRIC-OXIDE REVERSES THE DEPRESSED CONTRACTION OF CARDIAC MYOCYTES FROM ENDOTOXIN TREATED GUINEA-PIGS SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 762 EP 762 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003050 ER PT J AU HOLLENBERG, SM COBB, JP CUNNION, RE AF HOLLENBERG, SM COBB, JP CUNNION, RE TI DECREASED ARTERIOLAR RESPONSIVENESS TO NOREPINEPHRINE IN SEPTIC RATS IS REVERSED BY NG-METHYL-L-ARGININE SO CIRCULATION LA English DT Meeting Abstract C1 NICHHD,CTR CLIN,BETHESDA,MD 20892. NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 762 EP 762 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003048 ER PT J AU MARINNETO, JA ARRIGHI, JA BACHARACH, SL PERRONEFILARDI, P BONOW, RO DILSIZIAN, V AF MARINNETO, JA ARRIGHI, JA BACHARACH, SL PERRONEFILARDI, P BONOW, RO DILSIZIAN, V TI REGIONS WITH REVERSE REDISTRIBUTION AND ENHANCED THALLIUM UPTAKE AFTER REINJECTION ARE VIABLE BY PET SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 796 EP 796 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003184 ER PT J AU SHANDAS, R VALDESCRUZ, L JONES, M YAMADA, I AF SHANDAS, R VALDESCRUZ, L JONES, M YAMADA, I TI THE PROXIMAL FLOW CONVERGENCE TECHNIQUE CAN BE APPLIED TO COMPLEX PHYSIOLOGICAL FLOWS - ANIMAL STUDIES OF MITRAL REGURGITATION AND STENOSIS USING DIGITAL COLOR DOPPLER SO CIRCULATION LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 804 EP 804 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003216 ER PT J AU ZHANG, J JONES, M MURILLO, A YAMADA, I KANG, SU WEINTRAUB, R SHANDAS, R VALDESCRUZ, L AF ZHANG, J JONES, M MURILLO, A YAMADA, I KANG, SU WEINTRAUB, R SHANDAS, R VALDESCRUZ, L TI EFFECTS OF VARIATION OF ALIASING VELOCITY LIMIT ON THE ACCURACY OF COLOR M-MODE FLOW CONVERGENCE METHODS FOR ASSESSING MITRAL REGURGITATION - STUDIES IN INSTRUMENTED SHEEP YIELD A NEW MULTIPLE ALIAS METHOD SO CIRCULATION LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 805 EP 805 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003220 ER PT J AU WINGATE, SJ AF WINGATE, SJ TI A MODEL FOR QUALITY-OF-LIFE IN POSTMYOCARDIAL INFARCTION WOMEN SO CIRCULATION LA English DT Meeting Abstract C1 NIH,CTR CLIN,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 817 EP 817 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003269 ER PT J AU RASMUSSON, RL DAVIS, DG LIEBERMAN, M AF RASMUSSON, RL DAVIS, DG LIEBERMAN, M TI AMINO-ACID LOSS DURING REGULATORY VOLUME DECREASE IN CULTURED CHICK HEART-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 DUKE UNIV,DEPT CELL BIOL,DURHAM,NC 27706. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 826 EP 826 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003304 ER PT J AU BERTONI, AG MANKAD, S ADRIAN, S STERN, MD SILVERMAN, HS AF BERTONI, AG MANKAD, S ADRIAN, S STERN, MD SILVERMAN, HS TI IMPAIRED POSTHYPOXIC RELAXATION IN SINGLE CARDIAC MYOCYTES - ROLE OF PH1 AND INTRACELLULAR PHOSPHATE SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 828 EP 828 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003311 ER PT J AU MALINCHIK, S EPSTEIN, N FANANAPAZIR, L PODOLSKY, R HOROWITS, R AF MALINCHIK, S EPSTEIN, N FANANAPAZIR, L PODOLSKY, R HOROWITS, R TI ISOMETRIC TENSION OF SINGLE SKELETAL MYOFIBERS ASSOCIATED WITH DISTINCT MUTATIONS IN THE BETA-MYOSIN HEAVY-CHAIN GENE SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP 837 EP 837 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66003350 ER PT J AU PERRONEFILARDI, P BACHARACH, SL DILSIZIAN, V MAUREA, S FRANK, JA BONOW, RO AF PERRONEFILARDI, P BACHARACH, SL DILSIZIAN, V MAUREA, S FRANK, JA BONOW, RO TI REGIONAL LEFT-VENTRICULAR WALL THICKENING - RELATION TO REGIONAL UPTAKE OF FLUORODEOXYGLUCOSE-18 AND TL-201 IN PATIENTS WITH CHRONIC CORONARY-ARTERY DISEASE AND LEFT-VENTRICULAR DYSFUNCTION SO CIRCULATION LA English DT Article DE SYSTOLIC FUNCTION; MYOCARDIUM; TL-201; SCINTIGRAPHY; CORONARY ARTERY DISEASE; TOMOGRAPHY, POSITRON EMISSION ID POSITRON-EMISSION TOMOGRAPHY; ISCHEMIC-HEART-DISEASE; MYOCARDIAL BLOOD-FLOW; NUCLEAR MAGNETIC-RESONANCE; VIABLE MYOCARDIUM; HIBERNATING MYOCARDIUM; STRESS-REDISTRIBUTION; PERSISTENT DEFECTS; LATE REVERSIBILITY; METABOLIC-ACTIVITY AB Background. In previous studies comparing regional Tl-201 (Tl-201) and 18fluorodeoxyglucose (FDG) activity in patients with chronic coronary artery disease and left ventricular dysfunction, we hypothesized that regions with mild-to-moderate reduction in FDG activity and regions with mild-to-moderate irreversible Tl-201 defects after 3- to 4-hour redistribution represent viable myocardium. In the present study, regional FDG and Tl-201 activities were compared with regional systolic wall thickening by gated magnetic resonance imaging (MRI) to confirm the presence of viable myocardium in these territories. Methods and Results. Twenty-five patients with chronic stable coronary artery disease and left ventricular dysfunction (ejection fraction, 28+/-10) underwent exercise Tl-201 tomographic imaging (SPECT), using a reinjection protocol, positron emission tomography (PET) with FDG and (H2O)-O-15), and gated MRI. Matched SPECT, PET, and MRI tomograms were analyzed. From the PET data, 105 regions had matched reduction in FDG and blood flow, of which 69 regions had moderately reduced FDG uptake (50-79% uptake relative to a normal reference region) and 36 had severely reduced FDG uptake (<50% of normal activity). Regions with moderately reduced as compared with severely reduced FDG activity had greater end-diastolic wall thickness (9.4+/-2.6 versus 8.0+/-3.7 mm; p<0.05) and regional systolic wall thickening (1.7+/-2.7 versus -0.7+/-2.1 mm;p<0.01). From the SPECT data, 169 irreversible Tl-201 defects after 3-4-hour redistribution were identified, of which 70 were mild (>65 to <85% of maximal Tl-201 activity), 52 were moderate (50-65% of maximal activity), and 47 were severe (<50% of maximal activity). Regional systolic wall thickening was greater in regions with normal Tl-201 uptake (3.3+/-2.3 mm) as compared with all other regions. Regions showing only mild or moderate irreversible defects at redistribution, however, showed wall thickening (2.4+/-2.4 and 2.2+/-2.5 mm, respectively), which was similar to that observed in regions with reversible Tl-201 defects (2.1+/-2.2 mm). Only regions with severe irreversible defects at redistribution showed absence of thickening (-0.1+/-2.9 mm, p<0.01 versus all other groups). After Tl-201 reinjection, 12 of 47 (26%) regions with severe irreversible defects showed enhanced Tl-201 uptake. The impairment in regional systolic wall thickening was not significantly different between Tl-201 defects with and without enhanced Tl-201 uptake after reinjection. FDG activity, however, was present in all 12 regions (100%) with enhanced Tl-201 uptake after reinjection as compared with only five of 35 (14%) that were unchanged after reinjection (p<0.01). Conclusions. Therefore, preserved wall thickness and systolic wall thickening in regions with moderate reduction in blood flow and FDG activity, and in irreversible Tl-201 defects that are only mild-to-moderate, provide additional evidence that such regions represent viable myocardium. Moreover, the finding of metabolic activity and Tl-201 uptake in regions with reduced blood flow and absent wall thickening provides clinical evidence of hibernating myocardium in humans. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NIH,DEPT NUCL MED,BETHESDA,MD 20892. NR 39 TC 107 Z9 111 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 BP 1125 EP 1137 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JR938 UT WOS:A1992JR93800006 PM 1394920 ER PT J AU DIODATI, JG CANNON, RO EPSTEIN, SE QUYYUMI, AA AF DIODATI, JG CANNON, RO EPSTEIN, SE QUYYUMI, AA TI PLATELET HYPERAGGREGABILITY ACROSS THE CORONARY BED IN RESPONSE TO RAPID ATRIAL-PACING IN PATIENTS WITH STABLE CORONARY-ARTERY DISEASE SO CIRCULATION LA English DT Note DE PLATELETS; CORONARY ARTERY DISEASE; CORONARY CIRCULATION; WHOLE BLOOD IMPEDANCE AGGREGOMETRY ID ACUTE MYOCARDIAL-INFARCTION; SUBSTANCE PROSTAGLANDIN-X; RELAXING FACTOR; CLINICAL IMPLICATIONS; UNSTABLE ANGINA; WHOLE-BLOOD; THROMBOXANE RELEASE; TACHYCARDIA STRESS; THROMBUS FORMATION; ADENYLATE-CYCLASE AB Background. Platelet aggregation is believed to contribute to the precipitation of acute ischemic syndromes. Because physical activity has been proposed as one possible trigger in converting a patient with chronic coronary artery disease to one with an acute ischemic syndrome, we examined the hypothesis that platelets become activated when coronary blood flow velocities (and thereby shear stress) increase across an atherosclerotic bed. Methods and Results. During catheterization, 82 patients (36 with left coronary artery disease, 12 with only right coronary artery disease, and 34 with normal coronary arteries) had measurement of whole blood platelet aggregation performed on blood samples obtained simultaneously from the coronary sinus and aorta at rest, 2 minutes after onset of rapid atrial pacing, and 10 minutes after pacing was terminated. There was no arteriovenous difference in platelet aggregation under resting conditions in patients with versus those without coronary artery disease. Atrial pacing in patients with left coronary artery disease (greater-than-or-equal-to 50% stenosis in a major epicardial vessel) caused an increase in platelet aggregation in the coronary sinus blood (+64+/-9%, p<0.01) but not in arterial blood (2+/-8% decrease, p=NS). This increase was transient and returned nearly to baseline 10 minutes after termination of pacing. Patients with nonsignificant left coronary artery disease, those with normal coronary arteries, and patients with significant disease only in the right coronary artery (venous drainage not into the coronary sinus) did not show any changes in either the coronary sinus or arterial blood with atrial pacing. Conclusions. There is no evidence of platelet activation across a normal or an atherosclerotic coronary bed at rest. When coronary blood flow increases in the presence of significant (greater-than-or-equal-to 50%) narrowing of epicardial coronary arteries, however, platelets are activated and aggregate more easily. This mechanism may play a role in the precipitation of acute ischemic syndromes in patients with coronary artery disease. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 83 TC 41 Z9 41 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 OCT PY 1992 VL 86 IS 4 BP 1186 EP 1193 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JR938 UT WOS:A1992JR93800013 PM 1394926 ER PT J AU DOUEK, PC CORREA, R NEVILLE, R UNGER, EF SHOU, M BANAI, S FERRANS, VJ EPSTEIN, SE LEON, MB BONNER, RF AF DOUEK, PC CORREA, R NEVILLE, R UNGER, EF SHOU, M BANAI, S FERRANS, VJ EPSTEIN, SE LEON, MB BONNER, RF TI DOSE-DEPENDENT SMOOTH-MUSCLE CELL-PROLIFERATION INDUCED BY THERMAL-INJURY WITH PULSED INFRARED-LASERS SO CIRCULATION LA English DT Article DE LASER; INJURY, THERMAL; RESTENOSIS; CELLS, SMOOTH MUSCLE; ATHEROSCLEROSIS, ACCELERATED; NEOINTIMA ID BALLOON ANGIOPLASTY; CORONARY ANGIOPLASTY; ARTERIAL-WALL; MODEL; RABBIT; RESTENOSIS; TISSUE AB Background. Recently, laser-heated and radio frequency-heated balloon angioplasty techniques have been proposed as a means to treat or minimize dissection and elastic recoil but have been associated with a high rate of dinical restenosis. Similarly, pulsed laser angioplasty techniques proposed to minimize thermal injury while ablating obstructing atheroma have failed to reduce clinical restenosis. Because "hot balloon" and pulsed laser angioplasty create both mechanical and thermal injury, it has been difficult to discern the cause of the smooth muscle cell (SMC) proliferation resulting in restenosis and whether such magnitude of proliferation is predictable and dose related. This study was undertaken to explore these issues. Methods and Results. Localized thermal lesions accompanying efficient ablation were created with a pulsed Tm:YAG laser in nine rabbit aortas, which consistently led to a focal proliferation of SMC that filled the ablated region by 4 weeks. Transcutaneous Ho:YAG pulsed laser irradiation at multiple independent sites of 24 central rabbit ear arteries without ablation led to brief almost-equal-to 30-degrees-C thermal transients and thermal damage to the artery wall resulting in significant neointimal proliferation by 3 weeks and a mean cross-sectional narrowing of 59+/-17% at a dose of 390 mJ/mm2. Acute and chronic responses to varying total energy deposition were studied by histology after the rabbits were killed at 2 hours to 4 weeks. Arterial segments midway between laser injuries were unaffected and served as internal controls. Neointimal proliferation at 3 weeks after laser injury exhibited a clear dose dependence. Mean cross-sectional narrowing increased from 34+/-10% to 85+/-15% as laser fluence increased from 240 mJ/cm2 to 640 mJ/cm2 (r=0.84). Similarly, cross-sectional narrowing caused by SMC neointimal proliferation increased from 20+/-10% to 77+/-17% for a fixed surface irradiation as the depth of the most superficial arterial media decreased from 600 mum to 330 mum (r=0.94). Conclusions. Thermal injury to the arterial wall is a potent stimulus for SMC proliferation and may necessitate reduction in laser or thermal energy used for angioplasty. Moreover, a dose-response relation exists between the degree of thermal injury and SMC proliferative response. Hence, this technique could be used as a practical model of restenosis suitable for screening therapies for inhibition of SMC proliferation. C1 NHLBI,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3W13,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,ULTRASTRUCT SECT,BETHESDA,MD 20892. WASHINGTON HOSP CTR,DIV CARDIOL,WASHINGTON,DC 20010. RI Bonner, Robert/C-6783-2015 NR 33 TC 23 Z9 25 U1 0 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 BP 1249 EP 1256 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JR938 UT WOS:A1992JR93800020 PM 1394931 ER PT J AU DIODATI, JG CANNON, RO QUYYUMI, AA AF DIODATI, JG CANNON, RO QUYYUMI, AA TI PLATELET ACTIVATION IN CORONARY-ARTERY DISEASE - INDUCTION BY PHYSICAL AND MENTAL STRESS AND ATTENUATION BY NITROGLYCERIN, NITROPRUSSIDE, AND ASPIRIN SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1992 VL 86 IS 4 SU S BP S9 EP S9 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JT660 UT WOS:A1992JT66000024 ER PT J AU GAMBASSI, G SPURGEON, HA LAKATTA, EG BLANK, PS CAPOGROSSI, MC AF GAMBASSI, G SPURGEON, HA LAKATTA, EG BLANK, PS CAPOGROSSI, MC TI DIFFERENT EFFECTS OF ALPHA-ADRENERGIC AND BETA-ADRENERGIC STIMULATION ON CYTOSOLIC PH AND MYOFILAMENT RESPONSIVENESS TO CA2+ IN CARDIAC MYOCYTES SO CIRCULATION RESEARCH LA English DT Article DE ALPHA-ADRENOCEPTORS; BETA-ADRENOCEPTORS; CYTOSOLIC PH; CARDIAC MYOCYTES; CALCIUM; INDO-1; SNARF-1; MYOCARDIAL CONTRACTION ID PROTEIN-KINASE-C; MEDIATED PHOSPHOINOSITIDE BREAKDOWN; PROMOTING PHORBOL ESTERS; RAT VENTRICULAR MYOCYTES; CHICK HEART-CELLS; NA+/H+ EXCHANGE; INTRACELLULAR PH; SARCOPLASMIC-RETICULUM; PURKINJE-FIBERS; ALPHA-1-ADRENOCEPTOR STIMULATION AB Alpha-adrenergic stimulation (alpha-AS) and beta-adrenergic stimulation (beta-AS) of the myocardium are associated respectively with an increase and a decrease in myofilament responsiveness to Ca2+. We hypothesized that changes in cytosolic pH (pH(i)) may modulate these opposite actions of alpha-AS and beta-AS. The effects of alpha-AS (50-mu-M phenylephrine and 1-mu-M nadolol) and beta-AS (0.05-mu-M isoproterenol) on contraction and either cytosolic Ca2+ (Ca(i)) or pH(i) were assessed in adult rat ventricular myocytes bathed in bicarbonate buffer (pH 7.36+/-0.05). In cells loaded with the ester derivative (AM form) of indo-1, the 410/490-nm ratio of emitted fluorescence indexed Ca(i). Myofilament responsiveness to Ca2+ was assessed by the relaxation phase of the length-indo-1 fluorescence relation during a twitch. Alpha-AS and beta-AS shifted this relation in opposite directions, indicating that alpha-AS increased and beta-AS decreased myofilament responsiveness to Ca2+. In addition, the positive inotropic action of alpha-AS was associated with an increased Ca+ transient amplitude in 50% of the myocytes (n=12), whereas beta-AS always increased Ca(i) (n=5). In cells loaded with the fluorescent pH(i) probe SNARF-1 AM, the emitted 590/640-nm fluorescence is a measure of pH(i). The effect of alpha-AS on the extent of cell shortening during the twitch (ES) was expressed as the percentage of resting cell length. Both ES and pH(i) were assessed in myocytes bathed in 1.5 mM [Ca2+] and stimulated at 0.5 Hz (control ES, 7.4+/-1.5%; control pH(i), 7.11+/-0.05; n=10). Alpha-AS enhanced both ES (DELTA-ES, 1.8+/-0.6%; p<0.05) and pH(i) (DELTA-pH(i), 0.06+/-0.01; p<0.005), and there was a significant correlation between DELTA-ES and DELTA-pH(i) (r=0.76, p < 0.05). A similar effect of alpha-AS on pH(i) was observed in the absence of electrical stimulation (n=8). The alpha-AS-induced enhancement of ES and pH(i) was abolished by 10-mu-M ethylisopropylamiloride, a Na+-H+ exchange inhibitor (n=7). In additional experiments, myocytes were preincubated either with 0.2-mu-M 4-beta-phorbol 12-myristate 13-acetate (n=8) or with 5 nM staurosporine (n=8), which have been shown to downregulate and inhibit Ca2-activated phospholipid-dependent protein kinase C, respectively. In either group, alpha-AS had no effect on pH(i) and decreased ES to almost-equal-to 60% of control. In myocytes bathed in 0.5 mM [Ca2+] and stimulated at 0.2 Hz, beta-AS enhanced ES (control ES as percentage of resting cell length, 2.8+/-1.0%; DELTA-ES, 8.1+/-1.5%; n=7; p<0.005) but had no effect on pH(i) either during electrical stimulation (n=7) or at rest (n=11). In summary, under the conditions of this study, alpha-AS enhances myofilament response to Ca2+ and increases pH(i) via protein kinase C-mediated activation of Na+-H+ exchange. Cytosolic alkalinization contributes to the effect of alpha-AS to augment contraction amplitude. An enhanced Ca(i) transient occurs in 50% of the myocytes and is not an absolute requirement for the positive inotropic action of alpha-AS. In contrast, beta-AS does not affect pH(i), and cytosolic acidification is not the mechanism for the beta-AS-induced decrease in myofilament responsiveness to Ca2+. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. NR 68 TC 96 Z9 97 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT PY 1992 VL 71 IS 4 BP 870 EP 882 PG 13 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA JN856 UT WOS:A1992JN85600014 PM 1516160 ER PT J AU CAREW, BD AHN, SA BOICHOT, HD DIERENFELDT, BJ DOLAN, NA EDENS, TR WEINER, DH PROBSTFIELD, JL AF CAREW, BD AHN, SA BOICHOT, HD DIERENFELDT, BJ DOLAN, NA EDENS, TR WEINER, DH PROBSTFIELD, JL TI RECRUITMENT STRATEGIES IN THE STUDIES OF LEFT-VENTRICULAR DYSFUNCTION (SOLVD) - STRATEGIES FOR SCREENING AND ENROLLMENT IN 2 CONCURRENT BUT SEPARATE TRIALS SO CONTROLLED CLINICAL TRIALS LA English DT Article DE HEART FAILURE; CONGESTIVE; PATIENT PARTICIPATION; CONTROLLED CLINICAL TRIALS ID CLINICAL-TRIALS AB SOLVD was a double-masked, placebo-controlled trial whose initial sample size goal was to randomize 6100 participants into two concurrent trials: treatment and prevention. The objective was to determine if participants with severe left ventricular dysfunction (left ventricular ejection fraction less-than-or-equal-to 35%, with congestive heart failure (2569) and participants without overt heart failure (4228) had improved survival with angiotensin-converting enzyme inhibitors. Participants were identified from cardiac catheterization, echocardiography and radionuclide laboratories, and inpatient units. The treatment trial recruitment goal was attained 13 months ahead of schedule while recruitment for the prevention trial was extended 11 months beyond the scheduled time. Recruitment of relatively asymptomatic participants with a low ejection fraction in a hospital-based trial necessitated novel strategies. Coronary care units and clinics for follow-up of acute cardiac conditions, not typically employed in studies of chronic diseases, were useful recruitment sources. Different approaches to encourage participation also needed to be employed. Expanding selected entry criteria was evaluated and the success of varying strategies was reviewed. The authors recommend tailoring of strategies to the target population, staffing flexibility, principal investigator involvement, and broad entry criteria in recruitment activities. C1 NHLBI,CLIN TRIALS BRANCH,FED BLDG,ROOM 5C10,2550 WISCONSIN AVE,BETHESDA,MD 20892. DALHOUSIE UNIV,DIV CARDIOL,HALIFAX B3H 4H2,NS,CANADA. CATHOLIC UNIV LOUVAIN,DIV CARDIOL,B-1200 BRUSSELS,BELGIUM. VANDERBILT UNIV,MED CTR,SCH MED,DIV CARDIOL,NASHVILLE,TN 37232. MICHIGAN STATE UNIV,DEPT MED,E LANSING,MI 48824. UNIV ILLINOIS,DEPT MED,URBANA,IL 61801. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. UNIV N CAROLINA,CTR COLLABORAT STUDIES COORDINAT,DEPT BIOSTAT,CHAPEL HILL,NC 27514. NR 34 TC 18 Z9 18 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 1992 VL 13 IS 5 BP 325 EP 338 DI 10.1016/0197-2456(92)90035-X PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA JW213 UT WOS:A1992JW21300002 PM 1330437 ER PT J AU HARRISON, L GFROERER, J AF HARRISON, L GFROERER, J TI THE INTERSECTION OF DRUG-USE AND CRIMINAL BEHAVIOR - RESULTS FROM THE NATIONAL HOUSEHOLD SURVEY ON DRUG-ABUSE SO CRIME & DELINQUENCY LA English DT Article ID AGE; ADDICTION AB In 1991, questions on involvement in criminal behavior and being arrested and booked for a crime were added to the National Household Survey on Drug Abuse (NHSDA) to ascertain the relationship between dug use and criminal behavior. Analysis shows that drug use is a strong correlate of being booked for a criminal offense, but age is the more important correlate of criminal involvement. There were few differences in models predicting violent as opposed to property crime, although minority status was a more important predictor of violent crime, and poverty was a more important predictor of properly crime. Cocaine use was the most important covariate of being booked for a crime in large metropolitan areas that were oversampled in the 1991 NHSDA. RP HARRISON, L (reprint author), NIDA,DIV EPIDEMIOL & PREVENT RES,5600 FISHERS LANE,ROCKWALL 11,SUITE 615,ROCKVILLE,MD 20857, USA. NR 39 TC 68 Z9 68 U1 3 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0011-1287 J9 CRIME DELINQUENCY JI Crime Delinq. PD OCT PY 1992 VL 38 IS 4 BP 422 EP 443 DI 10.1177/0011128792038004002 PG 22 WC Criminology & Penology SC Criminology & Penology GA JP700 UT WOS:A1992JP70000002 ER PT J AU MAENO, M ONG, RC KUNG, HF AF MAENO, M ONG, RC KUNG, HF TI POSITIVE AND NEGATIVE REGULATION OF THE DIFFERENTIATION OF VENTRAL MESODERM FOR ERYTHROCYTES IN XENOPUS-LAEVIS SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Article DE XENOPUS-LAEVIS; ERYTHROPOIESIS; EMBRYONIC BLOOD ISLAND; EXPLANT; REGULATION ID LATERAL PLATE MESODERM; HEMATOPOIETIC-CELLS; BLOOD ISLAND; INDUCTION; EMBRYOS; ONTOGENY; CHIMERAS; MARKERS RP MAENO, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702, USA. NR 21 TC 29 Z9 29 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD OCT PY 1992 VL 34 IS 5 BP 567 EP 577 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA JY320 UT WOS:A1992JY32000010 ER PT J AU FRENZ, DA GALINOVICSCHWARTZ, V LIU, W FLANDERS, KC VANDEWATER, TR AF FRENZ, DA GALINOVICSCHWARTZ, V LIU, W FLANDERS, KC VANDEWATER, TR TI TRANSFORMING GROWTH-FACTOR BETA-1 IS AN EPITHELIAL-DERIVED SIGNAL PEPTIDE THAT INFLUENCES OTIC CAPSULE FORMATION SO DEVELOPMENTAL BIOLOGY LA English DT Article ID TGF-BETA; MESENCHYMAL CONDENSATION; DIFFERENTIAL EXPRESSION; CARTILAGE; LIMB; PATTERN; EMBRYO; CHONDROGENESIS; GENES; IDENTIFICATION C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP FRENZ, DA (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT OTOLARYNGOL,BRONX,NY 10461, USA. FU NIDCD NIH HHS [DC-00081, DC-00088]; NINDS NIH HHS [NS-07098] NR 39 TC 57 Z9 61 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT PY 1992 VL 153 IS 2 BP 324 EP 336 DI 10.1016/0012-1606(92)90117-Y PG 13 WC Developmental Biology SC Developmental Biology GA JR327 UT WOS:A1992JR32700014 PM 1397689 ER PT J AU BACH, LA RECHLER, MM AF BACH, LA RECHLER, MM TI INSULIN-LIKE GROWTH-FACTORS AND DIABETES SO DIABETES-METABOLISM REVIEWS LA English DT Review RP BACH, LA (reprint author), NIH,BLDG 10,RM 8D14,BETHESDA,MD 20892, USA. OI Bach, Leon/0000-0002-9062-1518 NR 0 TC 104 Z9 109 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-4221 J9 DIABETES METAB REV JI Diabetes-Metab. Rev. PD OCT PY 1992 VL 8 IS 3 BP 229 EP 257 PG 29 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KN662 UT WOS:A1992KN66200004 PM 1292913 ER PT J AU EGERTON, M ASHE, OR CHEN, D DRUKER, BJ BURGESS, WH SAMELSON, LE AF EGERTON, M ASHE, OR CHEN, D DRUKER, BJ BURGESS, WH SAMELSON, LE TI VCP, THE MAMMALIAN HOMOLOG OF CDC48, IS TYROSINE PHOSPHORYLATED IN RESPONSE TO T-CELL ANTIGEN RECEPTOR ACTIVATION SO EMBO JOURNAL LA English DT Article DE CELL CYCLE; PHOSPHORYLATION; SIGNAL TRANSDUCTION; LYMPHOCYTE-T ID PHOSPHOLIPASE C-GAMMA-1; SIGNAL TRANSDUCTION; PHOSPHATASE-ACTIVITY; PRECURSOR PROTEIN; GENE-EXPRESSION; ZETA-CHAIN; KINASE; YEAST; STIMULATION; CDNA AB Activation of T cells through the T cell antigen receptor (TCR) results in the rapid tyrosine phosphorylation of a number of cellular proteins, one of the earliest being a 100 kDa protein. We have sought to identify this 100 kDa substrate by partially purifying the protein by antiphosphotyrosine (APT) affinity purification, in order to obtain amino acid sequence data and, using this information, to isolate the cDNA clone encoding the molecule. We report here that the amino acid sequence data showed pp100 to be the murine equivalent of porcine valosin containing protein (VCP), a finding confirmed from the cloning and sequencing of the murine pp100 cDNA. Sequence analysis has shown VCP to be a member of a family of ATP binding, homo-oligomeric proteins, and the mammalian homolog of Saccharomyces cerevisiae cdc48p, a protein essential to the completion of mitosis in yeast. We also provide proof that both endogenous and expressed murine VCP are tyrosine phosphorylated in response to T cell activation. Thus we have identified a novel component of the TCR mediated tyrosine kinase activation pathway that may provide a link between TCR ligation and cell cycle control. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOLEC & CELLULAR BIOL,BOSTON,MA 02115. AMER RED CROSS,HOLLAND LAB,ROCKVILLE,MD 20850. RP EGERTON, M (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL-35762] NR 56 TC 120 Z9 122 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT PY 1992 VL 11 IS 10 BP 3533 EP 3540 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JN506 UT WOS:A1992JN50600006 PM 1382975 ER PT J AU MCCONVILLE, MJ TURCO, SJ FERGUSON, MAJ SACKS, DL AF MCCONVILLE, MJ TURCO, SJ FERGUSON, MAJ SACKS, DL TI DEVELOPMENTAL MODIFICATION OF LIPOPHOSPHOGLYCAN DURING THE DIFFERENTIATION OF LEISHMANIA-MAJOR PROMASTIGOTES TO AN INFECTIOUS STAGE SO EMBO JOURNAL LA English DT Article DE DIFFERENTIATION; GLYCOSYLATED PHOSPHATIDYLINOSITOL; LEISHMANIA; LIPOPHOSPHOGLYCAN ID GLYCOSYLATED-PHOSPHATIDYLINOSITOLS; SURFACE LIPOPHOSPHOGLYCAN; EXPRESSION; DONOVANI; RELEASE; FAMILY; METACYCLOGENESIS; GLYCOCONJUGATE; MACROPHAGES; GLYCOLIPIDS AB Protozoan parasites of the genus Leishmania produce the novel surface glycoconjugate, lipophosphoglycan (LPG), which is required for parasite infectivity. In this study we show that LPG structure is modified during the differentiation of L.major promastigotes from a less infectious form in logarithmic growth phase to a highly infectious 'metacyclic' form during stationary growth phase. In both stages, the LPGs comprise linear chains of phosphorylated oligosaccharide repeat units which are anchored to the membrane via a glycosyl-phosphatidylinositol glycolipid anchor. During metacyclogenesis there is (i) an approximate doubting in the average number of repeat units per molecule from 14 to 30, (ii) a pronounced decrease in the relative abundance of repeat units with side chains of beta-Gal or Gal-beta-1-3Gal-beta-1-, and a corresponding increase in repeat units with either no side chains or with side chains of Arap-alpha-1-2 Gal-beta-1- and (iii) a decrease in the frequency with which the glycolipid anchor is substituted with a single glucose-alpha-1-phosphate residue. While the majority of the LPG phosphoglycan chains are capped with the neutral disaccharide, Man-alpha-1-2Man, a significant minority of the chains appeared to terminate in non-phosphorylated repeat units and may represent incompletely capped species. We suggest that the developmental modification of LPG may be important in modulating the binding of promastigotes to receptors in the sandfly midgut and on human macrophages and in increasing the resistance of metacyclic promastigotes to complement-mediated lysis. C1 UNIV KENTUCKY,DEPT BIOCHEM,LEXINGTON,KY 40506. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP MCCONVILLE, MJ (reprint author), UNIV DUNDEE,DEPT BIOCHEM,DUNDEE DD1 4HN,SCOTLAND. RI Ferguson, Michael/F-7829-2010; OI Ferguson, Michael/0000-0003-1321-8714 FU Wellcome Trust NR 33 TC 185 Z9 189 U1 1 U2 5 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 OCT PY 1992 VL 11 IS 10 BP 3593 EP 3600 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JN506 UT WOS:A1992JN50600013 PM 1396559 ER PT J AU NELSON, KG TAKAHASHI, T LEE, DC LUETTEKE, NC BOSSERT, NL ROSS, K EITZMAN, BE MCLACHLAN, JA AF NELSON, KG TAKAHASHI, T LEE, DC LUETTEKE, NC BOSSERT, NL ROSS, K EITZMAN, BE MCLACHLAN, JA TI TRANSFORMING GROWTH FACTOR-ALPHA IS A POTENTIAL MEDIATOR OF ESTROGEN ACTION IN THE MOUSE UTERUS SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA; PROGESTERONE-RECEPTOR; HUMAN KERATINOCYTES; RIBONUCLEIC-ACID; EPITHELIAL-CELLS; GENE-EXPRESSION; EGF RECEPTOR; FACTOR-I; RAT; INDUCTION AB To better understand the role of peptide growth factors in sex steroid hormone-mediated growth of the female reproductive tract, the effect of estrogen on the expression of transforming growth factor-alpha (TGFalpha) in mouse uterus was investigated. Our results show that estrogen induces the expression of TGFalpha mRNA in the mouse uterus in a dose- and time-dependent manner. The up-regulation of TGFalpha transcripts occurs predominantly in uterine epithelial cells. RIA and Western blot analysis demonstrate that immunoreactive TGFalpha protein is secreted at high levels into mouse uterine luminal fluid after estrogen treatment. The induction of uterine TGFalpha mRNA is specific to estrogen; nonestrogenic steroids did not induce expression. Antibody specific to TGFalpha significantly reduces estrogen-mediated uterine growth, which supports the concept that TGFalpha is a mitogen for the reproductive tract. Analysis of TGFalpha/EGF receptors by binding, affinity labeling, and phosphorylation studies indicates that functional receptors are present in the mouse uterus after estrogen exposure. Thus, our data support a physiological role for TGFalpha and its receptor pathway in the female mouse reproductive tract. C1 UNIV N CAROLINA, LINEBERGER COMPREHENS CANC RES CTR, CHAPEL HILL, NC 27599 USA. UNIV N CAROLINA, DEPT MICROBIOL & IMMUNOL, CHAPEL HILL, NC 27599 USA. RP NELSON, KG (reprint author), NIEHS, REPROD & DEV TOXICOL LAB, BOX 12233, RES TRIANGLE PK, NC 27709 USA. NR 36 TC 162 Z9 162 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 OCT PY 1992 VL 131 IS 4 BP 1657 EP 1664 DI 10.1210/en.131.4.1657 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT904 UT WOS:A1992JT90400014 PM 1396310 ER PT J AU ADAMO, ML SHAO, ZM LANAU, F CHEN, JC CLEMMONS, DR ROBERTS, CT LEROITH, D FONTANA, JA AF ADAMO, ML SHAO, ZM LANAU, F CHEN, JC CLEMMONS, DR ROBERTS, CT LEROITH, D FONTANA, JA TI INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND RETINOIC ACID MODULATION OF IGF-BINDING PROTEINS (IGFBPS) - IGFBP-2, IGFBP-3, AND IGFBP-4 GENE-EXPRESSION AND PROTEIN SECRETION IN A BREAST-CANCER CELL-LINE SO ENDOCRINOLOGY LA English DT Article ID HUMAN-SKIN FIBROBLASTS; STIMULATED GROWTH; RECEPTOR; INHIBITION; CLONING; RAT; IDENTIFICATION; PROLIFERATION; INVITRO; CULTURE AB Retinoic acid (RA) blocks insulin-like growth factor-I (IGF-1) stimulation of proliferation in the MCF-7 breast carcinoma cell line, and this is associated with the appearance of 42- to 46-kilodalton (kDa) IGF-binding proteins(s) (IGFBPs) in the conditioned medium (CM), in addition to the approximately 34- and 27-kDa IGFBPs present in the CM of unstimulated cells. Using immunological, biochemical, and molecular biological criteria, we have identified the 27-kDa band as IGFBP-4, the 34-kDa band as IGFBP-2, and the 42- to 46-kDa band as IGFBP-3. IGF-I alone stimulated MCF-7 cell proliferation, and this was associated with a large increase in IGFBP-2 in the CM. RA alone resulted in increased IGFBP-4 levels and the appearance of IGFBP-3 in the CM. The combination of RA and IGF-1, which resulted in decreased cellular proliferation, was associated with the appearance of IGFBP-3 in the CM at levels far exceeding those seen with RA alone. The effect of IGF-I on IGFBP-2 levels and the synergistic action of IGF-I and RA on IGFBP-3 levels in CM were blocked by alphaIR3, a monoclonal antibody to the human IGF-I receptor, indicating that these effects required signal transduction through the IGF-I receptor. IGFBP-2, -3, and -4 mRNAs were detected in unstimulated MCF-7 cells. RA increased IGFBP-3 mRNA levels, suggesting that transcriptional events contribute to the RA stimulation of IGFBP-3 appearance in CM. In contrast, the increase in IGFBP-2 protein in CM after IGF-I treatment appeared to be greater than the increase in IGFBP-2 mRNA levels. The increase in IGFBP-3 protein in CM in response to the combination of RA and IGF-I was much greater than the increase in IGFBP-3 mRNA. These results suggest that the action of RA and IGF-I in combination to increase IGFBP-3 protein in CM is principally translational or posttranslational. We speculate that RA inhibition of IGF-I-stimulated MCF-7 cell proliferation may be due to IGFBP-3, or that increased levels of IGFBP-3 in response to growth inhibition represent a compensatory response. C1 NIDDKD, MOLEC & CELLULAR PHYSIOL SECT,BLDG 10,ROOM 8S243, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. UNIV N CAROLINA, SCH MED, DEPT MED, CHAPEL HILL, NC 27514 USA. UNIV MARYLAND, DEPT MED & CANC CTR, BALTIMORE, MD 21202 USA. VET ADM MED CTR, BALTIMORE, MD 21202 USA. NR 64 TC 103 Z9 104 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 OCT PY 1992 VL 131 IS 4 BP 1858 EP 1866 DI 10.1210/en.131.4.1858 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT904 UT WOS:A1992JT90400044 PM 1382963 ER PT J AU CHIKANZA, IC CHROUSOS, G PANAYI, GS AF CHIKANZA, IC CHROUSOS, G PANAYI, GS TI ABNORMAL NEUROENDOCRINE IMMUNE COMMUNICATIONS IN PATIENTS WITH RHEUMATOID-ARTHRITIS SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID LEWIS RATS; PROLACTIN; BROMOCRIPTINE C1 NICHHD,BETHESDA,MD 20892. RP CHIKANZA, IC (reprint author), UNIV LONDON,UNIV MED & DENT SCH GUYS & ST THOMAS HOSP,GUYS HOSP,DIV MED,RHEUMATOL UNIT,LONDON SE1 9RT,ENGLAND. NR 14 TC 32 Z9 32 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD OCT PY 1992 VL 22 IS 10 BP 635 EP 637 DI 10.1111/j.1365-2362.1992.tb01422.x PG 3 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA JT631 UT WOS:A1992JT63100001 PM 1459167 ER PT J AU GAZZINELLI, RT OSWALD, IP HIENY, S JAMES, SL SHER, A AF GAZZINELLI, RT OSWALD, IP HIENY, S JAMES, SL SHER, A TI THE MICROBICIDAL ACTIVITY OF INTERFERON-GAMMA-TREATED MACROPHAGES AGAINST TRYPANOSOMA-CRUZI INVOLVES AN L-ARGININE-DEPENDENT, NITROGEN OXIDE-MEDIATED MECHANISM INHIBITABLE BY INTERLEUKIN-10 AND TRANSFORMING GROWTH-FACTOR-BETA SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED MACROPHAGES; MURINE MACROPHAGES; CELL-LINE; CYTOKINE PRODUCTION; RESPIRATORY BURST; NITRIC-OXIDE; IFN-GAMMA; INVIVO; IL-10; LEISHMANIA AB The present study was carried out to determine the effector mechanism of anti-Trypanosoma cruzi activity by interferon (IFN)-gamma plus lipopolysaccharide (LPS)-treated macrophages. A macrophage cell line (IC-21) that failed to mount an appreciable oxidative burst was nevertheless found able to control T. cruzi growth after exposure to IFN-gamma alone or IFN-gamma plus LPS. Moreover, microbicidal functions of both inflammatory macrophages and IC-21 against T. cruzi was found to be inhibited in the presence of N(G)-monomethyl-L-arginine (N(G)MMA), a competitive inhibitor of L-arginine. Addition of supplemental L-arginine to the culture overcame the capacity of N(G)MMA to block activated macrophage anti-T. cruzi functions. The ability of N(G)MMA to reverse both parasite growth inhibition and killing by IFN-gamma plus LPS-activated macrophages was found to correlate with the suppression of nitrite accumulation in the culture supernatants. Together, these results implicate the L-arginine-dependent production of nitric oxide in T cruzi killing by activated macrophages. We also tested the ability of interleukin(IL)-10 and transforming growth factor (TGF)-beta, to block regulation of T cruzi growth in this system. Both IL-10 and TGF-beta inhibited anti-parasite function by IFN-gamma-activated macrophages, with an optimal dose of 100 units/ml and 0.5 ng/ml, respectively. Moreover, when used in combination, suboptimal doses of IL-10 and TGF-beta were found to produce a synergistic inhibitory effect in the regulation of T cruzi growth. The ability of IL-10 and TGF-beta to suppress microbicidal function was also positively correlated with inhibition of nitrite generation in macrophage culture supernatants. These results predict an in vivo role for IL-10 and TGF-beta in promoting parasite survival in the face of the host cell-mediated immune response. RP GAZZINELLI, RT (reprint author), NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI OSWALD, Isabelle/A-8497-2013 NR 53 TC 352 Z9 353 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1992 VL 22 IS 10 BP 2501 EP 2506 DI 10.1002/eji.1830221006 PG 6 WC Immunology SC Immunology GA JV594 UT WOS:A1992JV59400005 PM 1396957 ER PT J AU LESCH, KP HOUGH, CJ AULAKH, CS WOLOZIN, BL TOLLIVER, TJ HILL, JL AKIYOSHI, J CHUANG, DM MURPHY, DL AF LESCH, KP HOUGH, CJ AULAKH, CS WOLOZIN, BL TOLLIVER, TJ HILL, JL AKIYOSHI, J CHUANG, DM MURPHY, DL TI FLUOXETINE MODULATES-G PROTEIN ALPHA-S, ALPHA-Q, AND ALPHA-12 SUBUNIT MESSENGER-RNA EXPRESSION IN RAT-BRAIN SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Note DE G-PROTEINS; POLYMERASE CHAIN REACTION; MESSENGER RNA EXPRESSION; FLUOXETINE ID PHOSPHOLIPASE-C; DIVERSITY AB Signal-transducing G proteins are central to the coordination of receptor-effector communication. We have explored the effects of long-term fluoxetine administration on G-alpha(s), G-alpha(i1), G-alpha(i2), G-alpha(o), G-alpha(q) and G-alpha-12 mRNA expression in various rat brain regions using reverse transcriptase-polymerase chain reaction (RT-PCR)-mediated cross-species partial cDNA cloning, Northern blot analysis, and RNase protection assay techniques. Fluoxetine decreased G-alpha(s) mRNA in midbrain, while mRNA expression of the novel G protein a subunits, G-alpha(q) and G-alpha-12, was increased in neostriatum and frontal cortex. We conclude that in addition to post-translational modification, regulation of G protein function by antidepressant drugs may occur at the level of gene expression. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL UNIT,BETHESDA,MD 20892. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 15 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD OCT 1 PY 1992 VL 227 IS 2 BP 233 EP 237 DI 10.1016/0922-4106(92)90134-H PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JP464 UT WOS:A1992JP46400017 PM 1426031 ER PT J AU PATTERSON, BH KESSLER, LG WAX, Y BERNSTEIN, A LIGHT, L MIDTHUNE, DN PORTNOY, B TENNEY, J TUCKERMANTY, E AF PATTERSON, BH KESSLER, LG WAX, Y BERNSTEIN, A LIGHT, L MIDTHUNE, DN PORTNOY, B TENNEY, J TUCKERMANTY, E TI EVALUATION OF A SUPERMARKET INTERVENTION - THE NCI-GIANT FOOD EAT FOR HEALTH STUDY SO EVALUATION REVIEW LA English DT Article ID NUTRITION; PROGRAM; CANCER AB A 2-year supermarket intervention in 20 pair-matched stores tested whether a nutrition education program could produce changes in food purchasing behavior Food sales data for 2 intervention years were compared with baseline year data. The evaluation presented challenges related to the quasi-experimental study design and to the high variability and auto- and cross-sectional correlations in the data. A complex time series model was used to take these factors into account and to test for intervention effects. C1 NCI,APPL RES BRANCH,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,BIOSTAT CTR CLIN CANC RES,JERUSALEM,ISRAEL. INST SCI SOC,WASHINGTON,DC. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. GIANT FOOD INC,NUTR PROGRAMS,LANDOVER,MD. USDA,HOME ECON & HUMAN NUTR UNIT,WASHINGTON,DC 20250. RP PATTERSON, BH (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892, USA. NR 19 TC 9 Z9 9 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0193-841X J9 EVALUATION REV JI Eval. Rev. PD OCT PY 1992 VL 16 IS 5 BP 464 EP 490 DI 10.1177/0193841X9201600502 PG 27 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA JP745 UT WOS:A1992JP74500002 ER PT J AU MACIEJEWSKI, JP LIU, JM GREEN, SW WALSH, CE PLUMB, M PRAGNELL, IB YOUNG, NS AF MACIEJEWSKI, JP LIU, JM GREEN, SW WALSH, CE PLUMB, M PRAGNELL, IB YOUNG, NS TI EXPRESSION OF STEM-CELL INHIBITOR (SCI) GENE IN PATIENTS WITH BONE-MARROW FAILURE SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE STEM CELL INHIBITOR; MACROPHAGE INFLAMMATORY PROTEIN; BONE MARROW FAILURE ID MACROPHAGE INFLAMMATORY PROTEIN-1; COLONY FORMATION INVITRO; APLASTIC-ANEMIA; PROGENITOR CELLS; PROLIFERATION; INTERLEUKIN-1; CYTOKINE; MURINE; GROWTH; SUPPRESSION AB Stem cell inhibitor (SCI) has been shown to inhibit the proliferation of primitive progenitors. The inhibitor, a Product of bone marrow macrophages, activated lymphocytes, and monocytes, is identical to macrophage inflammatory protein (MIP-1alpha). We report homologous (SCI/hMIP-1-alpha) sequences in freshly isolated lymphocytes, monocytes, and granulocytes and have found that SCI mRNA can be induced in monocytes by lipopolysaccharide (LPS) and interleukins 1, 2, and 6. In contrast, interferon gamma (IFN-gamma) decreases the expression of SCI/hMIP-1alpha. Although only a low level expression of SCI/hMIP-1alpha mRNA can be detected in normal human bone marrow nucleated cells (NCBM), very significant increases in the levels of SCI/hMIP-1alpha RNA transcripts are observed in NCBM from patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). These data suggest that the expression of SCI/hMIP-1alpha in bone marrow may reflect dysregulated cytokine production and activation of the immune system that may possibly contribute to disease progression. C1 BEATSON INST CANC RES,WOLFSON LAB MOLEC PATHOL,GLASGOW G61 1BD,SCOTLAND. RP MACIEJEWSKI, JP (reprint author), NHLBI,CLIN HEMATOL BRANCH,CELL BIOL SECT,BETHESDA,MD 20892, USA. NR 43 TC 27 Z9 27 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 OCT PY 1992 VL 20 IS 9 BP 1112 EP 1117 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA JP952 UT WOS:A1992JP95200013 PM 1468544 ER PT J AU TAKASHIMA, H POLTORAK, M BECKER, JB FREED, WJ AF TAKASHIMA, H POLTORAK, M BECKER, JB FREED, WJ TI EFFECTS OF ADRENAL-MEDULLA GRAFTS ON PLASMA-CATECHOLAMINES AND ROTATIONAL BEHAVIOR SO EXPERIMENTAL NEUROLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; DOPAMINE-DENERVATED STRIATUM; NERVE GROWTH-FACTOR; RAT SCIATIC-NERVE; PARKINSONS-DISEASE; SUBSTANTIA NIGRA; AUTOLOGOUS TRANSPLANTATION; CHROMAFFIN TISSUE; ANIMAL-MODEL; NEURONS C1 UNIV MICHIGAN, DEPT PSYCHOL, ANN ARBOR, MI 48104 USA. UNIV MICHIGAN, NEUROSCI PROGRAM, ANN ARBOR, MI 48104 USA. RP ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, NEUROPSYCHIAT BRANCH, PRECLIN NEUROSCI SECT, WASHINGTON, DC 20032 USA. FU NINDS NIH HHS [NS01056, NS22157] NR 49 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1992 VL 118 IS 1 BP 24 EP 34 DI 10.1016/0014-4886(92)90019-M PG 11 WC Neurosciences SC Neurosciences & Neurology GA JR631 UT WOS:A1992JR63100004 PM 1397173 ER PT J AU HEALY, B AF HEALY, B TI CREATING OUR CHILDRENS NIH AND OTHER STRATEGIC CHALLENGES SO FASEB JOURNAL LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 1992 VL 6 IS 13 BP 3138 EP 3142 PG 5 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA JU512 UT WOS:A1992JU51200004 PM 1397834 ER PT J AU GOERING, PL GALLOWAY, WD CLARKSON, TW LORSCHEIDER, FL BERLIN, M ROWLAND, AS AF GOERING, PL GALLOWAY, WD CLARKSON, TW LORSCHEIDER, FL BERLIN, M ROWLAND, AS TI TOXICITY ASSESSMENT OF MERCURY-VAPOR FROM DENTAL AMALGAMS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID PITUITARY-HORMONE RESPONSE; SILVER TOOTH FILLINGS; ORAL AIR MERCURY; OCCUPATIONAL EXPOSURE; ALZHEIMERS-DISEASE; INORGANIC MERCURY; ELEMENTAL MERCURY; SPONTANEOUS-ABORTIONS; TRACE-ELEMENT; FETAL TISSUES C1 UNIV CALGARY,FAC MED,DEPT MED PHYSIOL,CALGARY T2N 4N1,ALBERTA,CANADA. UNIV ROCHESTER,SCH MED,CTR ENVIRONM HLTH SCI,ROCHESTER,NY 14642. UNIV LUND,INST ENVIRONM MED,S-22101 LUND,SWEDEN. NIEHS,RES TRIANGLE PK,NC 27709. RP GOERING, PL (reprint author), US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,ROCKVILLE,MD 20857, USA. NR 93 TC 41 Z9 42 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD OCT PY 1992 VL 19 IS 3 BP 319 EP 329 DI 10.1016/0272-0590(92)90169-I PG 11 WC Toxicology SC Toxicology GA JU086 UT WOS:A1992JU08600001 PM 1360929 ER PT J AU DUNNICK, JK HAILEY, JR AF DUNNICK, JK HAILEY, JR TI TOXICITY AND CARCINOGENICITY STUDIES OF QUERCETIN, A NATURAL COMPONENT OF FOODS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID STATISTICAL ISSUES; RATS; FLAVONOIDS; LESIONS; KIDNEY; RUTIN RP DUNNICK, JK (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 30 TC 117 Z9 118 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD OCT PY 1992 VL 19 IS 3 BP 423 EP 431 DI 10.1016/0272-0590(92)90181-G PG 9 WC Toxicology SC Toxicology GA JU086 UT WOS:A1992JU08600013 PM 1459373 ER PT J AU BRANNAN, CI BEDELL, MA RESNICK, JL EPPIG, JJ HANDEL, MA WILLIAMS, DE LYMAN, SD DONOVAN, PJ JENKINS, NA COPELAND, NG AF BRANNAN, CI BEDELL, MA RESNICK, JL EPPIG, JJ HANDEL, MA WILLIAMS, DE LYMAN, SD DONOVAN, PJ JENKINS, NA COPELAND, NG TI DEVELOPMENTAL ABNORMALITIES IN STEEL(17H) MICE RESULT FROM A SPLICING DEFECT IN THE STEEL FACTOR CYTOPLASMIC TAIL SO GENES & DEVELOPMENT LA English DT Article DE STEEL FACTOR; S(17H); ETHYLNITROSOUREA; RNA SPLICING; GERM CELL DEVELOPMENT; MAMMALS ID PRIMORDIAL GERM-CELLS; TYROSINE KINASE RECEPTOR; MESSENGER-RNA PRECURSORS; MEMBRANE-BINDING REGION; FOREST VIRUS E2-PROTEIN; C-KIT RECEPTOR; GROWTH-FACTOR; W-LOCUS; PROTO-ONCOGENE; GENE-PRODUCT AB The murine dominant White spotting (W) and Steel (Sl) loci encode the c-kit tyrosine kinase receptor and its cognate ligand steel factor (SLF), respectively. Mutations at either locus produce deficiencies in the same three migratory cell populations-those giving rise to pigment cells, germ cells, and blood cells. The identification of the gene products of these two loci combined with the plethora of W and Sl mutations available for molecular analysis offers a unique opportunity to dissect the role of a tyrosine kinase receptor and its cognate ligand during development in a fashion not possible for most other mammalian genes. Among the most interesting Sl mutations available for study are those that induce sterility in only one sex. In studies described here, we show that one of these alleles, Sl17H, which in the homozygous condition induces sterility in males but not females, is the result of a splicing defect in the SLF cytoplasmic tail. We also characterize the nature of the germ cell defects in male and female Sl17H mice and show that both sexes are affected equally during embryonic but not postnatal development. These studies provide new insights into the role of SLF in germ cell development and indicate that the cytoplasmic domain of SLF is important for its normal biological function. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. JACKSON LAB,BAR HARBOR,ME 04609. UNIV TENNESSEE,DEPT ZOOL,KNOXVILLE,TN 37996. IMMUNEX CORP,DEPT EXPTL HEMATOL,SEATTLE,WA 98101. IMMUNEX CORP,DEPT MOLEC BIOL,SEATTLE,WA 98101. RI Norman, Robert/A-1155-2007 OI Norman, Robert/0000-0002-3118-3896 FU NCI NIH HHS [N0I-CO-74101]; NICHD NIH HHS [HD-20575] NR 44 TC 117 Z9 120 U1 0 U2 1 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 OCT PY 1992 VL 6 IS 10 BP 1832 EP 1842 DI 10.1101/gad.6.10.1832 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA JT979 UT WOS:A1992JT97900002 PM 1383087 ER PT J AU AQUADRO, CF JENNINGS, RM BLAND, MM LAURIE, CC LANGLEY, CH AF AQUADRO, CF JENNINGS, RM BLAND, MM LAURIE, CC LANGLEY, CH TI PATTERNS OF NATURALLY-OCCURRING RESTRICTION MAP VARIATION, DOPA DECARBOXYLASE ACTIVITY VARIATION AND LINKAGE DISEQUILIBRIUM IN THE DDC GENE REGION OF DROSOPHILA-MELANOGASTER SO GENETICS LA English DT Article ID OVERLAPPING TRANSCRIPTION UNITS; MOLECULAR POPULATION-GENETICS; ACHAETE-SCUTE REGION; WHITE-LOCUS REGION; TRANSPOSABLE ELEMENTS; PHENOTYPIC VARIATION; STRUCTURAL GENE; ENZYME-ACTIVITY; MUTATION; POLYMORPHISM AB Forty-six second-chromosome lines of Drosophila melanogaster isolated from five natural populations were surveyed for restriction map variation in a 65-kb region surrounding the gene (Ddc) encoding dopa decarboxylase (DDC). Sixty-nine restriction sites were scored, 13 of which were polymorphic. Average heterozygosity per nucleotide was estimated to be 0.005. Eight large (0.7-5.0 kb) inserts, two small inserts (100 and 200 bp) and three small deletions (100-300 bp) were also observed across the 65-kb region. We see no evidence for a reduction in either nucleotide heterozygosity or insertion/deletion variation in the central 26-kb segment containing Ddc and a dense cluster of lethal complementation groups and transcripts (greater-than-or-equal-to 9 genes) compared to that seen in the adjacent regions (totaling 39 kb) in which only a single gene and transcript has been detected, or to that observed for other gene regions in D. melanogaster. The distribution of restriction site variation shows no significant departure from that expected under an equilibrium neutral model. However insertions and deletions show a significant departure from neutrality in that they are too rare in frequency, consistent with them being deleterious on average. Significant linkage disequilibrium among variants exists across much of the 65-kb region. Lower regional rates of recombination combined with the influence of polymorphic chromosomal inversions, rather than epistatic selection among genes in the dense cluster, probably are sufficient explanations for the creation and/or maintenance of the linkage disequilibrium observed in the Ddc region. We have also assayed adult DDC enzyme activity in these same lines. Twofold variation in activity among lines is observed within our sample. Significant associations are observed between level of DDC enzyme activity and restriction map variants. Surprisingly, one line with a 5.0-kb insert within an intron and one line with a 1.5-kb insert near the 5' end of Ddc each show normal adult DDC activities. C1 CORNELL UNIV,GENET & DEV SECT,ITHACA,NY 14853. DUKE UNIV,DEPT ZOOL,DURHAM,NC 27706. UNIV CALIF DAVIS,CTR POPULAT BIOL,DAVIS,CA 95616. RP AQUADRO, CF (reprint author), NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709, USA. FU NIGMS NIH HHS [R01 GM036431, GM36431, GM11546] NR 45 TC 26 Z9 26 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 1992 VL 132 IS 2 BP 443 EP 452 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA JQ146 UT WOS:A1992JQ14600014 PM 1358752 ER PT J AU JACKSON, CE YUHKI, N DESNICK, RJ HASKINS, ME OBRIEN, SJ SCHUCHMAN, EH AF JACKSON, CE YUHKI, N DESNICK, RJ HASKINS, ME OBRIEN, SJ SCHUCHMAN, EH TI FELINE ARYLSULFATASE-B (ARSB) - ISOLATION AND EXPRESSION OF THE CDNA, COMPARISON WITH HUMAN ARSB, AND GENE LOCALIZATION TO FELINE CHROMOSOME-A1 SO GENOMICS LA English DT Article ID AMINO-ACID SEQUENCES; PURIFICATION; CLONING; DNA; NUCLEOTIDE; POLYMERASE; DEFICIENCY C1 CUNY MT SINAI SCH MED,DIV MED & MOLEC GENET,100TH ST & 5TH AVE,NEW YORK,NY 10029. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. UNIV PENN,SCH VET MED,PATHOL SECT,PHILADELPHIA,PA 19104. UNIV PENN,SCH VET MED,MED GENET SECT,PHILADELPHIA,PA 19104. FU NICHD NIH HHS [5 T32 HD07105]; NIDDK NIH HHS [DK 25759] NR 33 TC 21 Z9 22 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 OCT PY 1992 VL 14 IS 2 BP 403 EP 411 DI 10.1016/S0888-7543(05)80233-2 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JR697 UT WOS:A1992JR69700026 PM 1427856 ER PT J AU GABRIEL, O ASHWELL, G AF GABRIEL, O ASHWELL, G TI TRITIATED BOROHYDRIDE REDUCTION OF CARBOHYDRATES - REDUCTION OF INDIVIDUAL MONOSACCHARIDES, ALONE OR IN GROUPS, RESULTS IN HIGHLY DIVERGENT SPECIFIC ACTIVITIES SO GLYCOBIOLOGY LA English DT Article DE ALDITOLS; ANALYSIS OF CARBOHYDRATE; REDUCTION OF CARBOHYDRATES; TRITIATED BOROHYDRIDE ID CHROMATOGRAPHY; SUGARS AB Reduction of carbohydrates by tritiated borohydride resulted in the production of alditols or glycosides with characteristically divergent specific radioactivities. Simultaneous reduction of individual sugars in the presence of a reference standard, talose, permitted the assignment of a unique specific radioactivity with respect to talitol as 100%. A variety of structures was examined, including neutral hexoses, free and acetylated aminosugars, ketohexoses and glycosides containing a fixed pyranose ring adjacent to a carbonyl group. In the latter case, the resulting steric hindrance severely restricted the incorporation of tritium. In both of the ketohexoses tested, the minor product of the two epimeric alditols exhibited the higher specific radio-activity. In all cases, reduction produced a characteristic and reproducible specific activity in which the values varied from 51 to 182% of that found for talose. These results are interpreted on the basis of generalizations concerning mechanism and predictive value. RP GABRIEL, O (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 17 TC 7 Z9 7 U1 0 U2 1 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 OCT PY 1992 VL 2 IS 5 BP 437 EP 443 DI 10.1093/glycob/2.5.437 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV146 UT WOS:A1992JV14600006 PM 1457972 ER PT J AU LUCEY, MR GRAHAM, DM MARTIN, P DIBISCEGLIE, A ROSENTHAL, S WAGGONER, JG MERION, RM CAMPBELL, DA NOSTRANT, TT APPELMAN, HD AF LUCEY, MR GRAHAM, DM MARTIN, P DIBISCEGLIE, A ROSENTHAL, S WAGGONER, JG MERION, RM CAMPBELL, DA NOSTRANT, TT APPELMAN, HD TI RECURRENCE OF HEPATITIS-B AND DELTA HEPATITIS AFTER ORTHOTOPIC LIVER-TRANSPLANTATION SO GUT LA English DT Article ID VIRUS-DNA; INFECTION; DISEASE; ANTIGEN; ANTIBODY; CELLS AB The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in the native liver increased the risk of HBV induced tissue damage in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function. C1 UNIV MICHIGAN,MED CTR,DEPT SURG,ANN ARBOR,MI 48109. UNIV MICHIGAN,MED CTR,DEPT PATHOL,ANN ARBOR,MI 48109. NATL INST DIABET & DIGEST & KIDNEY DIS,LIVER DIS SECT,BETHESDA,MD. RP LUCEY, MR (reprint author), UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,DIV GASTROENTEROL,3912 TAUBMAN CTR,ANN ARBOR,MI 48109, USA. NR 24 TC 64 Z9 66 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD OCT PY 1992 VL 33 IS 10 BP 1390 EP 1396 DI 10.1136/gut.33.10.1390 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JU201 UT WOS:A1992JU20100020 PM 1446866 ER PT J AU ROCKEN, M BREIT, R AF ROCKEN, M BREIT, R TI CONCOMITANCE OF ATOPIC-DERMATITIS AND PSORIASIS - REPLY SO HAUTARZT LA German DT Article C1 STADT KRANKENHAUS,DERMATOL & ALLERGOL ABT,W-8000 MUNICH 40,GERMANY. RP ROCKEN, M (reprint author), NIAID,ZZ,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0017-8470 J9 HAUTARZT JI Hautarzt PD OCT PY 1992 VL 43 IS 10 BP 666 EP 667 PG 2 WC Dermatology SC Dermatology GA JT221 UT WOS:A1992JT22100018 ER PT J AU FRIED, MW KORENMAN, JC DIBISCEGLIE, AM PARK, Y WAGGONER, JG MITSUYA, H HARTMAN, NR YARCHOAN, R BRODER, S HOOFNAGLE, JH AF FRIED, MW KORENMAN, JC DIBISCEGLIE, AM PARK, Y WAGGONER, JG MITSUYA, H HARTMAN, NR YARCHOAN, R BRODER, S HOOFNAGLE, JH TI A PILOT-STUDY OF 2',3'-DIDEOXYINOSINE FOR THE TREATMENT OF CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Article ID VIRUS-REPLICATION; CONTROLLED TRIAL; INVITRO; INHIBITION; AIDS; 2',3'-DIDEOXYNUCLEOSIDES; INTERFERON; FAILURE; CELLS AB The nucleoside analog 2',3'-dideoxyinosine, currently being used to treat patients infected with the human immunodeficiency virus, has been shown to inhibit viral replication in certain cell culture systems of hepatitis B virus and the duck model of chronic hepatitis B infection. We studied the effect of dideoxyinosine on viral replication in patients with chronic hepatitis B. In the initial dose-finding phase, patients received sequential 2-wk courses of dideoxyinosine in escalating doses of 3, 6 and 9 mg/kg/day. In the second, long-term treatment phase, patients received dideoxyinosine at a dose of 9 mg/kg/day for 12 wk. Dideoxyinosine was given orally in three divided doses. The effects of dideoxyinosine on hepatitis B were assessed by serial measurements of ALT, hepatitis B virus DNA and DNA polymerase activity in serum. Six patients completed the dose-finding phase, and five patients continued into the long-term treatment phase. No significant differences were seen in serum aminotransferases, hepatitis B virus DNA levels or DNA polymerase activity at any time during treatment when compared with pretreatment levels. All patients remained positive for HBeAg during treatment and during 6 mo of follow-up. Thus at the doses tested, dideoxyinosine had no appreciable effect on viral replication in patients with chronic hepatitis B. C1 NCI,BETHESDA,MD 20892. RP FRIED, MW (reprint author), NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BLDG 10,RM 9C 103B,BETHESDA,MD 20892, USA. NR 19 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP 861 EP 864 DI 10.1002/hep.1840160402 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR883 UT WOS:A1992JR88300001 PM 1398494 ER PT J AU CARBONE, D AF CARBONE, D TI THE P53 KNOCKOUT - GONE BUT NOT FORGOTTEN SO HEPATOLOGY LA English DT Note RP CARBONE, D (reprint author), USN,MED ONCOL BRANCH,NCI,BETHESDA,MD 20899, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP 1094 EP 1096 DI 10.1002/hep.1840160439 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR883 UT WOS:A1992JR88300038 PM 1398492 ER PT J AU ADAMS, DH STIFF, L TANAKA, Y YANNELLI, JR SHAW, S AF ADAMS, DH STIFF, L TANAKA, Y YANNELLI, JR SHAW, S TI HEPATOCYTE GROWTH-FACTOR AND TRANSFORMING GROWTH FACTOR-ALPHA INDUCE HUMAN LYMPHOCYTE-T MIGRATION INVITRO SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20817. NCI,SURG BRANCH,BETHESDA,MD 20817. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A95 EP A95 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000203 ER PT J AU ADANIA, RS SILVA, AEB DIBISCEGLIE, AM BORDIN, JO LANZONI, VP FERRAZ, MLG AF ADANIA, RS SILVA, AEB DIBISCEGLIE, AM BORDIN, JO LANZONI, VP FERRAZ, MLG TI HEPATIC HISTOLOGY IN APPARENTLY HEALTHY BLOOD-DONORS WITH HEPATITIS-C VIRAL-INFECTION CONFIRMED BY PCR SO HEPATOLOGY LA English DT Meeting Abstract C1 ESCOLA PAULISTA MED SCH,SAO PAULO,BRAZIL. NIH,HEPATITIS STUDIES SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A194 EP A194 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000597 ER PT J AU BERGASA, NV THOMAS, DA VERGALLA, J TURNER, ML JONES, EA AF BERGASA, NV THOMAS, DA VERGALLA, J TURNER, ML JONES, EA TI SERUM EXTRACTS FROM CHOLESTATIC PATIENTS INDUCE NALOXONE-REVERSIBLE CENTRALLY-MEDIATED FACIAL SCRATCHING IN MONKEYS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 2 TC 6 Z9 6 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A152 EP A152 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000431 ER PT J AU BERGASA, NV ALLING, DW TALBOT, TL SWAIN, MG FRIED, MW FONG, TL YURDAYDIN, C SCHMITT, JM WALKER, EC TURNER, ML JONES, EA AF BERGASA, NV ALLING, DW TALBOT, TL SWAIN, MG FRIED, MW FONG, TL YURDAYDIN, C SCHMITT, JM WALKER, EC TURNER, ML JONES, EA TI NALOXONE AMELIORATES THE PRURITUS OF CHOLESTASIS - RESULTS OF A DOUBLE-BLIND RANDOMIZED PLACEBO-CONTROLLED TRIAL SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NIAID,DIV INTRAMURAL RES,BETHESDA,MD 20892. NIH,APPL CLIN ENGN SECT,BETHESDA,MD 20892. NR 2 TC 6 Z9 6 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A152 EP A152 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000429 ER PT J AU BERGASA, NV SABOL, SL YOUNG, SW KLEINER, DE JONES, EA AF BERGASA, NV SABOL, SL YOUNG, SW KLEINER, DE JONES, EA TI THE OPIOID SYSTEM IN CHOLESTASIS - FETAL ABILITY TO EXPRESS PREPROENKEPHALIN MESSENGER-RNA IS REGAINED IN ADULT-RAT LIVER BY PROLIFERATING BILE DUCTULES SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NHLBI,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 3 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A92 EP A92 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000191 ER PT J AU BUKH, J MILLER, RH PURCELL, RH AF BUKH, J MILLER, RH PURCELL, RH TI SEQUENCE VARIABILITY OF HEPATITIS-C VIRUS GENOMES COLLECTED WORLDWIDE SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A106 EP A106 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000247 ER PT J AU BURRA, P ELIAS, E NEWMAN, W ADAMS, DH AF BURRA, P ELIAS, E NEWMAN, W ADAMS, DH TI ELEVATED CIRCULATING LEVELS OF E-SELECTIN, FACTOR-VIII RELATED ANTIGEN AND HYALURONATE PROVIDE EVIDENCE FOR ENDOTHELIAL-CELL DAMAGE AND DYSFUNCTION IN SEVERE ALCOHOLIC HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract C1 QUEEN ELIZABETH HOSP,LIVER UNIT,BIRMINGHAM B15 2TH,W MIDLANDS,ENGLAND. OTSUKA PHARMACEUT CO LTD,ROCKVILLE,MD. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A77 EP A77 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000132 ER PT J AU DIBISCEGLIE, AM KRAWCZYNSKI, K BRAZZEAL, D HOOFNAGLE, JH AF DIBISCEGLIE, AM KRAWCZYNSKI, K BRAZZEAL, D HOOFNAGLE, JH TI HEPATITIS-C VIRAL-ANTIGEN (HCVAG) IN LIVER - EFFECT OF ANTIVIRAL THERAPY SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. CTR DIS CONTROL,ATLANTA,GA 30333. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A131 EP A131 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000346 ER PT J AU FARCI, P ALTER, HJ WONG, D OGATA, N MILLER, R SHAPIRO, M PURCELL, R AF FARCI, P ALTER, HJ WONG, D OGATA, N MILLER, R SHAPIRO, M PURCELL, R TI ATTEMPTS TO NEUTRALIZE HEPATITIS-C VIRUS (HCV) INVITRO WITH PLASMA FROM A CHRONICALLY INFECTED PATIENT - EVALUATION IN CHIMPANZEES SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. BIOGUAL INC,ROCKVILLE,MD 20850. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A105 EP A105 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000241 ER PT J AU FRIED, MW DIBISCEGLIE, AM STRAUS, SE SAVARESE, B BEAMES, MP HOOFNAGLE, JH AF FRIED, MW DIBISCEGLIE, AM STRAUS, SE SAVARESE, B BEAMES, MP HOOFNAGLE, JH TI FIAU, A NEW ORAL ANTIVIRAL AGENT, PROFOUNDLY INHIBITS HBV DNA IN PATIENTS WITH CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,HEPATITIS STUDIES SECT,BETHESDA,MD. NIAID,BETHESDA,MD 20892. NR 0 TC 37 Z9 39 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A127 EP A127 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000328 ER PT J AU HSIA, CC DIBISCEGLIE, AM TABOR, E AF HSIA, CC DIBISCEGLIE, AM TABOR, E TI IMMUNOHISTOCHEMICAL STAINING FOR RB TUMOR SUPPRESSOR GENE-PRODUCT IN HUMAN HEPATOCELLULAR-CARCINOMA (HCC) SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIADDKD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A57 EP A57 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000052 ER PT J AU JOLLEY, CS ABRIL, ER MARTINEZ, F EARNEST, DL AF JOLLEY, CS ABRIL, ER MARTINEZ, F EARNEST, DL TI UNIQUE BIPHASIC RESPONSE OF KC FUNCTION TO VARYING CONCENTRATIONS OF ETHANOL INVITRO IS MODIFIED BY LONG-TERM ETHANOL FEEDING SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV ARIZONA,COLL MED,NIAAA,SPECIALIZED ALCOHOL RES CTR,DEPT INTERNAL MED,TUCSON,AZ 85824. UNIV ARIZONA,COLL MED,NIAAA,SPECIALIZED ALCOHOL RES CTR,DEPT FAMILY & COMMUNITY MED,TUCSON,AZ 85824. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A163 EP A163 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000473 ER PT J AU MIMMS, LT BARBOSA, L CUNNINGHAM, M VALLARI, D HOLLINGER, FB STEVENS, CE AACH, RD MOSLEY, JW AF MIMMS, LT BARBOSA, L CUNNINGHAM, M VALLARI, D HOLLINGER, FB STEVENS, CE AACH, RD MOSLEY, JW TI COINFECTION OF HCV AND HBV IN POSTTRANSFUSION HEPATITIS PATIENTS FROM THE TRANSFUSION-TRANSMITTED VIRUSES STUDY SO HEPATOLOGY LA English DT Meeting Abstract C1 ABBOTT LABS,N CHICAGO,IL 60064. NHLBI,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. NEW YORK BLOOD CTR,NEW YORK,NY 10021. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV SO CALIF,LOS ANGELES,CA 90089. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A69 EP A69 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000097 ER PT J AU MISHRA, L BANKERT, L VOYLES, N GEARHART, J MISHRA, B KORMAN, L MEZEY, E AF MISHRA, L BANKERT, L VOYLES, N GEARHART, J MISHRA, B KORMAN, L MEZEY, E TI CHARACTERIZATION OF DIFFERENTIALLY EXPRESSED MESSENGER-RNAS IN MOUSE EMBRYONIC LIVER SO HEPATOLOGY LA English DT Meeting Abstract C1 VET ADM MED CTR,DEPT MED,WASHINGTON,DC. GEORGETOWN UNIV,WASHINGTON,DC 20007. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT PHYSIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A186 EP A186 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000565 ER PT J AU PREISEGGER, KH RIEGELNEGG, D SILVERMAN, JA GANT, TW BROWN, P THORGEIRSSON, SS DENK, H AF PREISEGGER, KH RIEGELNEGG, D SILVERMAN, JA GANT, TW BROWN, P THORGEIRSSON, SS DENK, H TI INDUCTION OF MALLORY BODY FORMATION IN MOUSE-LIVER IS ASSOCIATED WITH MODULATION OF P-GLYCOPROTEIN EXPRESSION SO HEPATOLOGY LA English DT Meeting Abstract C1 GRAZ UNIV,INST PATHOL,A-8010 GRAZ,AUSTRIA. NIH,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A137 EP A137 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000370 ER PT J AU SHINDO, M AKATSUKA, T DIBISCEGLIE, AM DONETS, M SCAGLIONE, L HOOFNAGLE, JH FEINSTONE, SM AF SHINDO, M AKATSUKA, T DIBISCEGLIE, AM DONETS, M SCAGLIONE, L HOOFNAGLE, JH FEINSTONE, SM TI A CAPTURE ASSAY FOR HCV RNA USING A HUMAN MONOSPECIFIC ANTIBODY TO CORE ANTIGEN OF HEPATITIS-C VIRUS (HCV) SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,HEPATITIS STUDIES SECT,BETHESDA,MD 20892. US FDA,CBER,HEPATITIS RES LAB,BETHESDA,MD 20014. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A70 EP A70 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000103 ER PT J AU SILVA, AEB MCMAHON, BJ PARKINSON, AJ HOOFNAGLE, JH DIBISCEGLIE, AM AF SILVA, AEB MCMAHON, BJ PARKINSON, AJ HOOFNAGLE, JH DIBISCEGLIE, AM TI HBV DNA BY PCR IN INDIVIDUALS WITH ANTI-HBC AS THE ONLY MARKER OF HEPATITIS-B VIRUS-INFECTION SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,HEPATITIS STUDIES SECT,BETHESDA,MD 20892. CTR DIS CONTROL,ARTIC INVEST LAB,ANCHORAGE,AK. ALASKA NATIVE MED CTR,ANCHORAGE,AK. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A65 EP A65 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000084 ER PT J AU SWAIN, MG PATCHEV, V CHROUSOS, G JONES, EA AF SWAIN, MG PATCHEV, V CHROUSOS, G JONES, EA TI UP-REGULATION OF HYPOTHALAMIC VASOPRESSIN IN BILE-DUCT RESECTED RATS - A NOVEL COMPENSATORY RESPONSE IN CHOLESTASIS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A152 EP A152 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000430 ER PT J AU SWAIN, MG VERGALLA, J JONES, EA AF SWAIN, MG VERGALLA, J JONES, EA TI PLASMA ENKEPHALINASE - A NEW MARKER OF CHOLESTASIS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A152 EP A152 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000428 ER PT J AU SWAIN, MG VERGALLA, J JONES, EA AF SWAIN, MG VERGALLA, J JONES, EA TI ACCUMULATION IN PLASMA OF CRYPTIC ENKEPHALINS, INCLUDING THE POTENT OPIOID AGONIST BAM-22P, IN ACUTE CHOLESTASIS IN THE RAT SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A151 EP A151 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000427 ER PT J AU TERAN, JC MULLEN, KD KOC, S HOOFNAGLE, JH MCCULLOUGH, AJ AF TERAN, JC MULLEN, KD KOC, S HOOFNAGLE, JH MCCULLOUGH, AJ TI MARKERS OF HEPATIC FIBROGENESIS IN PATIENTS WITH CHRONIC HEPATITIS-B TREATED WITH ALPHA-INTERFERON SO HEPATOLOGY LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NIH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A67 EP A67 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000091 ER PT J AU URRUTIA, R RIVOLTA, MN NEGRINI, C MCNIVEN, MA KACHAR, B AF URRUTIA, R RIVOLTA, MN NEGRINI, C MCNIVEN, MA KACHAR, B TI GENERATION OF EXPRESSED SEQUENCE TAGS FOR MOUSE-LIVER GENES USING UNFRACTIONATED CDNA PRIMARY LIBRARIES CONSTRUCTED IN M13 SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDCD,CELLULAR BIOL LAB,BETHESDA,MD 20892. NIDCD,MOLEC BIOL LAB,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,CTR BASIC RES DIGEST DIS,ROCHESTER,MN 55905. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A189 EP A189 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000574 ER PT J AU YURDAYDIN, C WONG, G BASILE, AS JONES, EA AF YURDAYDIN, C WONG, G BASILE, AS JONES, EA TI EFFICACY OF BENZODIAZEPINE RECEPTOR (BZR) ANTAGONISTS IN IMPROVING HEPATIC-ENCEPHALOPATHY (HE) MAY BE RELATED TO THEIR AFFINITY FOR DIAZEPAM INSENSITIVE RECEPTORS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NIDDK,NEUROSCI LAB,BETHESDA,MD. NR 1 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A86 EP A86 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000166 ER PT J AU YURDAYDIN, C ROTHMANN, RB VERGALLA, J BASILE, AS JONES, EA AF YURDAYDIN, C ROTHMANN, RB VERGALLA, J BASILE, AS JONES, EA TI IS THE OPIOID SYSTEM IMPLICATED IN HEPATIC-ENCEPHALOPATHY SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NIDDK,NEUROSCI LAB,BETHESDA,MD. NIDA,CLIN PSYCHOPHARMACOL LAB,BALTIMORE,MD. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1992 VL 16 IS 4 BP A86 EP A86 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JR380 UT WOS:A1992JR38000167 ER PT J AU ANDERSON, WF AF ANDERSON, WF TI THE JUNE RAC MEETING SO HUMAN GENE THERAPY LA English DT Editorial Material RP ANDERSON, WF (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,7D-18,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 1992 VL 3 IS 5 BP 459 EP 460 DI 10.1089/hum.1992.3.5-459 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA JX234 UT WOS:A1992JX23400001 PM 1420446 ER PT J AU POLYMEROPOULOS, MH HONG X MERRIL, CR AF POLYMEROPOULOS, MH HONG, X MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D9S147E LOCUS SO HUMAN MOLECULAR GENETICS LA English DT Note C1 ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, WASHINGTON, DC 20032 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1992 VL 1 IS 7 BP 549 EP 549 DI 10.1093/hmg/1.7.549-a PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JV142 UT WOS:A1992JV14200020 PM 1307259 ER PT J AU WEI, L LIN, SZ TAJIMA, A NAKATA, H ACUFF, V PATLAK, C PETTIGREW, K FENSTERMACHER, J AF WEI, L LIN, SZ TAJIMA, A NAKATA, H ACUFF, V PATLAK, C PETTIGREW, K FENSTERMACHER, J TI CEREBRAL GLUCOSE-UTILIZATION AND BLOOD-FLOW IN ADULT SPONTANEOUSLY HYPERTENSIVE RATS SO HYPERTENSION LA English DT Article DE BLOOD CIRCULATION; GLUCOSE; DEOXYGLUCOSE; AUTORADIOGRAPHY; HYPERTENSION, ESSENTIAL ID BRAIN; METABOLISM AB Not only blood pressure but also behavioral activity, brain morphology, and cerebral ventricular size differ between young spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. This suggests that cerebral blood flow and cerebral metabolism may vary between these two rat strains. To test this hypothesis, we measured local cerebral glucose utilization in 31 brain areas of 26-30-week-old rats. Local cerebral blood How was also assessed in these same areas. Cerebral glucose utilization was measured by the 2-deoxyglucose method; cerebral blood flow was determined by the iodoantipyrene method. In virtually all gray matter structures, the apparent rate of glucose utilization was lower in SHR than in normotensive WKY rats; the interstrain differences varied significantly among structures and were statistically significant (uncorrected t tests) in 14 of 28 gray matter areas. Local cerebral blood flow was fairly similar in the two rat strains. The coupling of blood flow to glucose utilization varied significantly among brain areas in normotensive WKY rats as well as in SHR. In a number of gray matter structures, the coupling of flow to metabolism differed between hypertensive and normotensive animals. These data suggest that for many brain areas, either glucose utilization or glucose partitioning differs between WKY rats and SHR. C1 SUNY STONY BROOK,HLTH SCI CTR,DEPT NEUROL SURG,TR-080,STONY BROOK,NY 11794. NIMH,DIV APPL & SERV RES,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL-35791] NR 23 TC 38 Z9 39 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 1992 VL 20 IS 4 BP 501 EP 510 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JQ605 UT WOS:A1992JQ60500007 PM 1398885 ER PT J AU SAUL, A YEGANEH, F HOWARD, RJ AF SAUL, A YEGANEH, F HOWARD, RJ TI CONSERVATION OF REPEATING STRUCTURES IN THE PFEMP2 MESA PROTEIN OF PLASMODIUM-FALCIPARUM SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Note ID MEMBRANE; ERYTHROCYTES; PARASITE; SURFACE C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 7 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD OCT PY 1992 VL 70 BP 353 EP 355 DI 10.1038/icb.1992.45 PN 5 PG 3 WC Cell Biology; Immunology SC Cell Biology; Immunology GA KC410 UT WOS:A1992KC41000009 PM 1478701 ER PT J AU SAUL, A YEGANEH, F HOWARD, RJ AF SAUL, A YEGANEH, F HOWARD, RJ TI CLONING AND CHARACTERIZATION OF A NOVEL MULTICOPY, REPETITIVE SEQUENCE OF PLASMODIUM-FALCIPARUM, REP51 SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Note ID DNA C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 4 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD OCT PY 1992 VL 70 BP 357 EP 359 DI 10.1038/icb.1992.46 PN 5 PG 3 WC Cell Biology; Immunology SC Cell Biology; Immunology GA KC410 UT WOS:A1992KC41000010 PM 1339406 ER PT J AU GAZZINELLI, RT HARTLEY, JW FREDRICKSON, TN CHATTOPADHYAY, SK SHER, A MORSE, HC AF GAZZINELLI, RT HARTLEY, JW FREDRICKSON, TN CHATTOPADHYAY, SK SHER, A MORSE, HC TI OPPORTUNISTIC INFECTIONS AND RETROVIRUS-INDUCED IMMUNODEFICIENCY - STUDIES OF ACUTE AND CHRONIC INFECTIONS WITH TOXOPLASMA-GONDII IN MICE INFECTED WITH LP-BM5 MURINE LEUKEMIA VIRUSES SO INFECTION AND IMMUNITY LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; CD4+ T-CELLS; C57BL/6 MICE; IFN-GAMMA; LYMPHOCYTES-T; INDUCTION; ENCEPHALITIS; RESISTANCE; LYMPHOMAS; ANTIBODY AB Mice infected with LP-BM5 murine leukemia viruses develop a syndrome, termed mouse AIDS (MAIDS), characterized by increasingly severe immunodeficiency and progressive lymphoproliferation. Virus-infected mice were examined for the ability to resist acute infection and to control chronic infection with the protozoan Toxoplasma gondii, a major opportunistic pathogen of individuals infected with human immunodeficiency virus. Mice infected with the retroviruses for 2 or 4 weeks responded normally to challenge with the parasite, but mice inoculated with the protozoan 8 or 12 weeks after viral infection died with acute disease due to T. gondii. Increased sensitivity to acute infection was associated with a reduced ability to produce gamma interferon (IFN-gamma) and with established changes in CD4+ T-cell function. Mice latently infected with T. gondii and then inoculated with the retrovirus mixture were found to reactivate the parasite infection, with 30 to 40% of dually infected animals dying between 5 and 16 weeks after viral infection. Reactivation was associated with reduced proliferation and impaired production of IFN-gamma in response to stimulation with soluble T. gondii antigens or to concanavalin A. Continuing resistance to lethal reactivation in the remaining mice was shown to require CD8+ T cells and expression of IFN-gamma. In addition, it was found that chronic infection with T. gondii altered the course of MAIDS by inhibiting the progression of splenomegaly and immunodeficiency and reducing the expression of both the helper and etiologic defective viruses. These results support previous studies which indicate that infection with T. gondii is controlled by synergistic interactions between CD4+ and CD8+ T cells, the functions of which are progressively impaired during the course of MAIDS. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NCI,REGISTRY EXPTL CANC,BETHESDA,MD 20892. RP GAZZINELLI, RT (reprint author), NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 NR 41 TC 54 Z9 56 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1992 VL 60 IS 10 BP 4394 EP 4401 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JP779 UT WOS:A1992JP77900055 PM 1328058 ER PT J AU MASUR, H AF MASUR, H TI PROPHYLAXIS AND THERAPY FOR PNEUMOCYSTIS PNEUMONIA - WHERE ARE WE SO INFECTIOUS AGENTS AND DISEASE-REVIEWS ISSUES AND COMMENTARY LA English DT Article DE PNEUMOCYSTIS PNEUMONIA; AIDS; HIV; TRIMETHOPRIM-SULFAMETHOXAZOLE; PENTAMIDINE; CLINDAMYCIN; PRIMAQUINE; ATOVAQUONE ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CARINII PNEUMONIA; TRIMETHOPRIM-SULFAMETHOXAZOLE; AEROSOLIZED PENTAMIDINE; FIBEROPTIC BRONCHOSCOPY; ADJUNCTIVE THERAPY; CONTROLLED TRIAL; DIAGNOSIS; CORTICOSTEROIDS; AIDS AB The armamentarium of drugs to treat and to prevent Pneumocystis pneumonia has expanded substantially over the past decade. In all patient populations trimethoprim-sulfamethoxazole is the preferred regimen for both acute treatment and prophylaxis. Clindamycin-primaquine and atovaquone are both effective agents for acute therapy but there are no data yet suggesting that they are preferable to trimethoprim-sulfamethoxazole. Corticosteroid therapy is now standard for severe AIDS-associated Pneumocystis pneumonia, and should probably be used in other patient populations with severe pneumocystis pneumonia as well. RP MASUR, H (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,BETHESDA,MD 20892, USA. NR 57 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1056-2044 J9 INFECT AGENT DIS JI Infect. Agents Dis.-Rev. Issues Comment. PD OCT PY 1992 VL 1 IS 5 BP 270 EP 278 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KD520 UT WOS:A1992KD52000006 PM 1344666 ER PT J AU PRUZANSKI, W WILMORE, DW SUFFREDINI, A MARTICH, GD HOFFMAN, AGD BROWNING, JL STEFANSKI, E STERNBY, B VADAS, P AF PRUZANSKI, W WILMORE, DW SUFFREDINI, A MARTICH, GD HOFFMAN, AGD BROWNING, JL STEFANSKI, E STERNBY, B VADAS, P TI HYPERPHOSPHOLIPASEMIA-A2 IN HUMAN VOLUNTEERS CHALLENGED WITH INTRAVENOUS ENDOTOXIN SO INFLAMMATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; GROUP-II PHOSPHOLIPASE-A2; SMOOTH-MUSCLE CELLS; SEPTIC SHOCK; SYNOVIAL-FLUID; EXTRACELLULAR PHOSPHOLIPASE-A2; CIRCULATING PHOSPHOLIPASE-A2; SOLUBLE PHOSPHOLIPASE-A2; RHEUMATOID-ARTHRITIS; GENE-EXPRESSION AB Phospholipase A2 (PLA2) activity was measured in the serum of 23 individuals infused intravenously with endotoxin (EN) at a dose of 4 ng/kg body weight. A marked increase in PLA2 was noted 3 h after EN challenge (mean 828 +/- 513 units/ml), reached its maximum at 24 h after the challenge (mean 2667 +/- 2442 units/ml), and was still evident at 48 h (mean 763 +/- 366 units/ml). In contrast, TNF levels were maximal (mean 712 +/- 375 pg/ml) 90 min after the EN challenge and subsided to very low values (5 +/- 5 pg/ml) 5 h after the challenge. There was a positive correlation between the maximum response of TNF and that of PLA2 (r = 0.82, P < 0.01). Administration of ibuprofen or pentoxifylline did not alter the PLA2 response. EN challenge did not affect serum pancreatic PLA2 concentration or that of the lysosomal cationic enzyme, lysozyme. Neutralizing antibody against human recombinant (synovial type) PLA2 completely abolished PLA2 activity in the sera tested. We conclude that EN infusions cause marked intravascular release of non-pancreatic secretory PLA2 and that the magnitude of this response seems to be related to the prior generation of TNF. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. BIOGEN INC,DEPT CELL BIOL,CAMBRIDGE,MA. UNIV LUND,DEPT PHYSIOL CHEM,S-22101 LUND,SWEDEN. RP PRUZANSKI, W (reprint author), UNIV TORONTO,INFLAMMAT RES GRP,TORONTO M5S 1A1,ONTARIO,CANADA. OI Browning, Jeffrey/0000-0001-9168-5233 NR 57 TC 37 Z9 37 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0360-3997 J9 INFLAMMATION JI Inflammation PD OCT PY 1992 VL 16 IS 5 BP 561 EP 570 DI 10.1007/BF00918980 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA JQ958 UT WOS:A1992JQ95800013 PM 1428127 ER PT J AU HU, N DAWSEY, SM WU, M BONNEY, GE HE, LJ HAN, XY FU, M TAYLOR, PR AF HU, N DAWSEY, SM WU, M BONNEY, GE HE, LJ HAN, XY FU, M TAYLOR, PR TI FAMILIAL AGGREGATION OF ESOPHAGEAL CANCER IN YANGCHENG COUNTY, SHANXI PROVINCE, CHINA SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article AB Oesophageal cancer is the second most common cause of cancer death in China and is particularly prevalent in northern China. Genetic factors have been studied less than environmental factors in the aetiology of this disease. This study was conducted to evaluate familial aggregation of oesophageal cancer. All households in Yangcheng County were interviewed in 1979 to determine family history of oesophageal cancer. In 1989, vital status for all family members from three Yangcheng villages was determined and re-interviews were conducted among families who reported a positive family history of oesophageal cancer in 1979. Risk of oesophageal cancer was evaluated by comparing family and individual rates of oesophageal cancer during the 1979-1989 interval stratified by the number of family members with oesophageal cancer prior to 1979. More families with prior oesophageal cancer history reported new oesophageal cancer deaths during the follow-up period than families without prior history (19% versus 5%). Oesophageal cancer rates increased with increasing positivity of family history, and adjustment for other risk factors did not substantially alter this result. We conclude that these data provide evidence for familial aggregation of oesophageal cancer. C1 NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. CHINESE ACAD MED SCI,INST CANC,DEPT CELL BIOL,BEIJING,PEOPLES R CHINA. YANGCHENG CTY CANC INST,SHANXI,PEOPLES R CHINA. SHANXI TUMOR HOSP,TAIYUAN,PEOPLES R CHINA. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. NR 10 TC 66 Z9 69 U1 0 U2 1 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 OCT PY 1992 VL 21 IS 5 BP 877 EP 882 DI 10.1093/ije/21.5.877 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JX020 UT WOS:A1992JX02000008 PM 1468848 ER PT J AU SCHWEINFEST, CW PAPAS, TS AF SCHWEINFEST, CW PAPAS, TS TI SUBTRACTION HYBRIDIZATION - AN APPROACH TO THE ISOLATION OF GENES DIFFERENTIALLY EXPRESSED IN CANCER AND OTHER BIOLOGICAL-SYSTEMS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE SUBTRACTIVE HYBRIDIZATION; DIFFERENTIAL HYBRIDIZATION; CDNA CLONING; PHAGEMID; PERT; PCR ID CDNA LIBRARIES; MESSENGER-RNAS; DNA-SEQUENCES; PHOTOACTIVATABLE BIOTIN; ENZYMATIC AMPLIFICATION; PROTEIN-SYNTHESIS; COLON-CARCINOMA; HEPATIC CANCER; GROWTH-FACTOR; CLONING AB Subtraction hybridization allows for the isolation and identification of genes which are differentially expressed in different cell types. It allows for such isolation without any a priori knowledge of the sequence or function of the target gene. The only requirement is that there be a difference in the relative abundance of the nucleic acid (mRNA or genomic DNA) in the two cell types being compared. In contrast to differential hybridization, cDNA clones representing mRNAs of very low abundance (0.001% to 0.1%) can be discerned using subtraction hybridization. The concept, applications and techniques of performing subtraction hybridization is discussed. RP SCHWEINFEST, CW (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21701, USA. NR 55 TC 10 Z9 10 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1992 VL 1 IS 5 BP 499 EP 506 PG 8 WC Oncology SC Oncology GA JV122 UT WOS:A1992JV12200001 PM 21584572 ER PT J AU HUPPI, K SIWARSKI, D GOODNIGHT, J SKURLA, RM MUSHINSKI, JF AF HUPPI, K SIWARSKI, D GOODNIGHT, J SKURLA, RM MUSHINSKI, JF TI ALTERNATIVE SPLICING OF PVT-1 TRANSCRIPTS IN MURINE LYMPHOCYTIC-B NEOPLASMS ACCOMPANIES AMPLIFICATION AND CHROMOSOMAL TRANSLOCATION SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE PVT-1 GENE; LYMPHOCYTIC-B NEOPLASMS; AMPLIFICATION; CHROMOSOMAL TRANSLOCATION ID T-CELL LYMPHOMAS; C-MYC ONCOGENE; ACUTE NONLYMPHATIC LEUKEMIA; ACID RECEPTOR-GAMMA; BURKITTS-LYMPHOMA; HOMOLOGOUS SEQUENCES; PLASMACYTOMAS; LOCUS; REGION; MLVI-1 AB The Pvt-1 region lies approximately 260 kb 3' of the c-myc proto-oncogene on mouse chromosome 15. Chromosomal translocation or viral integration into the region of Pvt-1 in B-cell or T-cell neoplasms appears to up-regulate c-myc expression by some unknown mechanism. Recent isolations of Pvt-1-encoding cDNAs from both mouse and human tissues indicate that transcripts of Pvt-1 can be found in multiple forms. To elucidate the nature of these transcripts in the mouse, we have analyzed cDNAs from AJ9, an immortalized Ly-1+ B-lymphocytic cell line in which myc/Pvt-1 have been co-amplified, and from ABPC20, a plasmacytoma that contains a t(6;15) translocation in the region of Pvt-1. Alternatively spliced transcripts of Pvt-1 are evident, but a stretch of 57 bp makes up the amino-terminus in each of these cDNAs. This region, designated Pvt-1a, is part of exon 1 and is also found within a 140 aa open reading frame (ORF), the longest Pvt-1 ORF established to date. Pvt-1a also shows homology at the amino acid level with two enzymes associated with transport in E. coli, glutamine permease operon protein glnQ and glycerophosphoryl diester phosphodiesterase glpQ. We predict that such chimeric mRNAs generated in mouse B-cell lymphomas and plasmacytomas with amplified or translocated Pvt-1 sequences may encode an in-frame segment of Pvt-1a. RP HUPPI, K (reprint author), NCI,GENET LAB,MOLEC GENET SECT,BLDG 37,ROOM 2B-21,BETHESDA,MD 20892, USA. NR 33 TC 6 Z9 6 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1992 VL 1 IS 5 BP 525 EP 532 PG 8 WC Oncology SC Oncology GA JV122 UT WOS:A1992JV12200004 PM 21584575 ER PT J AU HARRIS, CC HIROHASHI, S AF HARRIS, CC HIROHASHI, S TI UNITED-STATES-JAPAN SEMINAR ON GENOMIC INSTABILITY DURING CARCINOGENESIS AND TUMOR PROGRESSION SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Editorial Material C1 NATL CANC CTR,RES INST,DIV PATHOL,5-1-1 TSUKIJI,CHUO KU,TOKYO 104,JAPAN. NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 OCT PY 1992 VL 83 IS 10 BP 1108 EP 1111 PG 4 WC Oncology SC Oncology GA JU004 UT WOS:A1992JU00400015 PM 1360469 ER PT J AU THORGEIRSSON, SS AF THORGEIRSSON, SS TI THE LEC RAT - AN ANIMAL-MODEL FOR HUMAN HEPATITIS AND HEPATOCELLULAR-CARCINOMA SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Editorial Material ID HEREDITARY HEPATITIS RP THORGEIRSSON, SS (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,3C28,BETHESDA,MD 20892, USA. NR 10 TC 0 Z9 0 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 OCT PY 1992 VL 83 IS 10 BP UR1 EP UR1 PG 1 WC Oncology SC Oncology GA JU004 UT WOS:A1992JU00400001 ER PT J AU PHAIR, J HOOVER, D HUPRIKAR, J DETELS, R KASLOW, R RINALDO, C SAAH, A AF PHAIR, J HOOVER, D HUPRIKAR, J DETELS, R KASLOW, R RINALDO, C SAAH, A TI THE SIGNIFICANCE OF WESTERN-BLOT ASSAYS INDETERMINATE FOR ANTIBODY TO HIV IN A COHORT OF HOMOSEXUAL BISEXUAL MEN SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE WESTERN BLOT ASSAY; HIV SEROCONVERSION ID MULTICENTER AIDS COHORT; VIRUS TYPE-1 HIV-1; INFECTION; TESTS; RISK AB The objective of this study was to determine the frequency and significance of nondiagnostic Western blot (WB) assays in homosexual/bisexual men at risk of infection with HIV-1. The presence of a positive enzyme-linked antibody assay (EIA) confirmed by a positive WB was used as evidence of infection and seroconversion. Indeterminate WB assays were defined as reactions to only one viral gene product of HIV-1. Three analyses were conducted to (a) determine the frequency of such reactions in men who, during a 4-year period, did not develop diagnostic serologic reactions; (b) determine, retrospectively, the preseroconversion frequency of indeterminate WB assays in 286 men who seroconverted; and (c) evaluate in vitro production of specific antibody by peripheral blood mononuclear cells (PBMCs) as a method of indicating whether or not an indeterminate WB assay represents HIV-1 infection. Reactions to products of gag, pol, or env were noted in 8.0, 4.0, and 6.7% of 1,595 first-visit tests of men who remained seroneptive for 4 years. Indeterminate reactions occurred in 204 men with negative EIAs who subsequently seroconverted and in 82 men with positive EIAs preconversion. Supernatants harvested from PBMCs of 2 of 36 seroconverters obtained one or two visits preseroconversion and cultured with pokeweed mitogen were antibody-positive. All were positive at the visit, with diagnostic serology. None of the supernatants from cells of 19 men with EIA-negative WB-indeterminate serologic assays were antibody-positive. Our results suggest that persistently EIA-negative homosexual/bisexual men who have indeterminate WB assays are unlikely to be infected with HIV-1. In contrast, EIA-positive, WB-indeterminate serologic assays in this cohort were frequently associated with subsequent seroconversion. C1 NORTHWESTERN UNIV, SCH MED, HOWARD BROWN MEM CLIN, CHICAGO, IL 60611 USA. JOHNS HOPKINS SCH HYG & PUBL HLTH, CTR DATA COORDINATING, BALTIMORE, MD USA. UNIV CALIF LOS ANGELES, SCH PUBL HLTH, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA 90024 USA. NIAID, BALTIMORE, MD USA. UNIV PITTSBURGH, SCH PUBL HLTH, PITTSBURGH, PA 15260 USA. FU PHS HHS [N01-A1-32535, N01-A1-72676, N01-A1-72634] NR 14 TC 7 Z9 7 U1 2 U2 2 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 OCT PY 1992 VL 5 IS 10 BP 988 EP 992 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JN550 UT WOS:A1992JN55000004 PM 1453328 ER PT J AU GERGEN, PJ TURKELTAUB, PC AF GERGEN, PJ TURKELTAUB, PC TI THE ASSOCIATION OF INDIVIDUAL ALLERGEN REACTIVITY WITH RESPIRATORY-DISEASE IN A NATIONAL SAMPLE - DATA FROM THE 2ND NATIONAL-HEALTH AND NUTRITION EXAMINATION SURVEY, 1976-80 (NHANES-II) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE ASTHMA; ALLERGIC RHINITIS; CHRONIC RHINITIS; SINUSITIS; ALLERGY; NHANES-II ID SKIN-TEST REACTIVITY; HOUSE-DUST MITE; UNITED-STATES POPULATION; ASTHMATIC-CHILDREN; CHANGING PATTERNS; CHILDHOOD ASTHMA; POLLEN ALLERGENS; IGE ANTIBODIES; RAGWEED POLLEN; GRASS-POLLEN AB The independent association of individual allergen reactivity with respiratory disease was evaluated with use of the second National Health and Nutrition Examination Survey, a sample of the U.S. white civilian population, ages 6 to 24 years (n = 4295). Eight, 1:20 wt/vol, 50% glycerol, unstandardized extracts were administered by prick puncture. Allergen reactivity was reported as the percent with a mean erythema diameter 10.5 mm or greater at 20 minutes. Only the prevalence of asthma and allergic rhinitis increased with the increasing number of positive allergen skin tests. The independent association of individual allergen reactivity with respiratory disease was quantified with logistic models that included other allergen reactivity, age, sex, smoking, and region. Asthma was associated with reactivity to house dust (odds ratio, 2.9; 95% confidence interval [CI] 1.7 to 5) and Alternaria (odds ratio, 5.1; 95% CI: 2.9 to 8.9). Allergic rhinitis was associated with reactivity to ragweed (odds ratio, 2.3; 95% CI: 1.5 to 3.3); ryegrass (odds ratio, 2.8; 95% CI: 1.8 to 4.3); house dust (odds ratio, 2.5; 95% CI: 1.6 to 3.9); Alternaria (odds ratio, 2.3; 95% CI: 1.5 to 3.4). Asthma only (without allergic rhinitis) was associated with dust and Alternaria. Allergic rhinitis only (without asthma) was associated with ryegrass, ragweed, and house dust. When both asthma and allergic rhinitis were present, only house dust and Alternaria remained associated. These findings highlight the association of specific allergens with upper and lower respiratory diseases and the interactions among coexisting respiratory diseases. C1 US FDA,CTR BIOL EVALUAT & RES,ALLERGY & IMMUNOCHEM LAB,BETHESDA,MD 20014. RP GERGEN, PJ (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,SOLAR ROOM 4A29,BETHESDA,MD 20892, USA. NR 42 TC 169 Z9 171 U1 0 U2 8 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 1992 VL 90 IS 4 BP 579 EP 588 DI 10.1016/0091-6749(92)90130-T PN 1 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA JT995 UT WOS:A1992JT99500003 PM 1401641 ER PT J AU WHITE, MV KALINER, MA AF WHITE, MV KALINER, MA TI MEDIATORS OF ALLERGIC RHINITIS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE ALLERGIC RHINITIS; MAST CELLS; MEDIATOR RELEASE; NASAL MUCOSA; NEUROPEPTIDES ID HUMAN NASAL-MUCOSA; MAST-CELLS; SECRETIONS; PROTEIN; PEPTIDE; IGE AB Although histamine is the principal mediator of the immediate allergic reaction, other inflammatory mediators as well as neuropeptides also contribute to rhinorrhea and nasal congestion. Within minutes of exposure to allergen, mast cells produce histamine, leukotriene C4, and prostaglandin D2. A concomitant increase occurs in neuropeptides and bradykinin. In vitro mast cell activation also leads to the release of tumor necrosis factor-alpha, several interleukins, and granulocyte-macrophage colony-stimulating factor. Because all these various mediators and neuropeptides may play a role in producing rhinorrhea and congestion, antihistamines alone cannot control all of the symptoms of allergic rhinitis. However, the combination of antihistamines with topical corticosteroids can inhibit the generation, release, and activity of most if not all of the mediators potentially involved in the allergic response. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,11C205,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 39 TC 78 Z9 80 U1 1 U2 2 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 OCT PY 1992 VL 90 IS 4 SU S BP 699 EP 704 DI 10.1016/0091-6749(92)90155-U PN 2 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA JV009 UT WOS:A1992JV00900001 PM 1401652 ER PT J AU SIMONS KALINER NACLERIO TOWNLEY AF SIMONS KALINER NACLERIO TOWNLEY TI INHIBITION OF MEDIATOR RELEASE - COMMENTARY AND DISCUSSION SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Discussion C1 UNIV MANITOBA,DEPT PEDIAT & CHILD HLTH,WINNIPEG R3T 2N2,MANITOBA,CANADA. UNIV MANITOBA,ALLERGY & CLIN IMMUNOL SECT,WINNIPEG R3T 2N2,MANITOBA,CANADA. NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CLIN IMMUNOL,BALTIMORE,MD 21205. CREIGHTON UNIV,SCH MED,DEPT MED,CTR ALLERG DIS,DIV ALLERGY,OMAHA,NE 68178. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 1992 VL 90 IS 4 SU S BP 725 EP 728 PN 2 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA JV009 UT WOS:A1992JV00900005 ER PT J AU SHRAGER, RI AF SHRAGER, RI TI ANALYTIC MODELS FOR NONLINEAR CURVE-FITTING OF FORWARD-RATE BINDING DATA, WITH APPLICATIONS TO HEMOGLOBIN SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE MATHEMATICAL MODEL; NONLINEAR CURVE FITTING; HEMOGLOBIN LIGAND BINDING; FORWARD RATE CONSTANT ID INTERMEDIATE COMPOUNDS AB The experimental procedure of Perrella et al. (1983, J. Biol. Chem. 258, 4511-4517) can reveal most of the intermediate ligation states of hemoglobin either at equilibrium or in a kinetic reaction. In this paper, a model of stepwise ligand binding, under conditions of negligible reverse reaction, is derived with particular attention to hemoglobin. The model leads to a two-phase procedure. First, the ratios of the forward rates are determined by fitting the model to normalized concentrations vs. saturation. Second (optionally), an auxiliary relation is used to deduce the scale factor for the rates that make the model consistent with time information if such is available. The procedure has been applied to hemoglobin binding of the ligands carbon monoxide (this paper) and ferricyanide (manuscript in preparation). RP SHRAGER, RI (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD OCT PY 1992 VL 25 IS 2-3 BP 113 EP 124 DI 10.1016/0165-022X(92)90003-S PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JW134 UT WOS:A1992JW13400003 PM 1491097 ER PT J AU SHERMAN, SS TOBIN, JD HOLLIS, BW GUNDBERG, CM ROY, TA PLATO, CC AF SHERMAN, SS TOBIN, JD HOLLIS, BW GUNDBERG, CM ROY, TA PLATO, CC TI BIOCHEMICAL PARAMETERS ASSOCIATED WITH LOW BONE-DENSITY IN HEALTHY-MEN AND WOMEN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID VITAMIN-D STATUS; NORMAL ELDERLY WOMEN; POSTMENOPAUSAL WOMEN; PRIMARY HYPERPARATHYROIDISM; CREATININE CLEARANCE; PARATHYROID-HORMONE; SERUM OSTEOCALCIN; GLA-PROTEIN; CALCIUM; AGE AB A causal role in age-related bone loss has been attributed to alterations in vitamin D status, the bone mineral regulating hormones, and/or renal function. We assessed biochemical parameters of bone metabolism and renal function in healthy subsets of young and old men (n = 191) and women (n = 120) and evaluated the relationships between these parameters and bone mineral density (BMD) in the radius, spine, and femur. There were no significant associations between BMD at any site and serum 25-OHD, 1,25-(OH)2D, PTH, or creatinine clearance in either young men or in young or old women, after controlling for age. In old men, however, lower radius BMD was significantly related to higher PTH and higher 1,25-(OH)2D and marginally related to lower 25-OHD values. In young men, there were unexpected but significant associations between lower femoral neck BMD and higher serum osteocalcin and urinary calcium/creatinine excretion after age adjustment. In old women, lower spine and radius BMD was also significantly correlated with higher serum osteocalcin. In this healthy, vitamin D-replete population, there were significant cross-sectional declines in BMD in the femur in young and old men and at all sites in old women. Elevated remodeling may be an important feature that contributes to reduced femoral BMD in young men and reduced spine and radius BMD in old women. However, compromised renal function or levels of 1,25-(OH)2D or elevated PTH appear to be neither necessary nor relevant as determinants of osteopenia in the spine or femur in these normal, healthy men and women. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. MED UNIV S CAROLINA,CHILDRENS HOSP,DEPT PEDIAT,CHARLESTON,SC 29425. YALE UNIV,SCH MED,DEPT ORTHOPED,NEW HAVEN,CT 06510. NR 34 TC 77 Z9 78 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 1992 VL 7 IS 10 BP 1123 EP 1130 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT992 UT WOS:A1992JT99200002 PM 1456082 ER PT J AU VESTAL, DJ RANSCHT, B AF VESTAL, DJ RANSCHT, B TI GLYCOSYL PHOSPHATIDYLINOSITOL ANCHORED T-CADHERIN MEDIATES CALCIUM-DEPENDENT, HOMOPHILIC CELL-ADHESION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID UVOMORULIN-CATENIN COMPLEX; MOLECULE UVOMORULIN; CYTOPLASMIC DOMAIN; NEURITE OUTGROWTH; GENE FAMILY; EXPRESSION; PROTEIN; IDENTIFICATION; GLYCOPROTEIN; MEMBRANE AB Cadherins are a family of cell adhesion molecules that exhibit calcium-dependent, homophilic binding. Their function depends on both an HisAlaVal sequence in the first extracellular domain, EC1, and the interaction of a conserved cytoplasmic region with intracellular proteins. T-cadherin is an unusual member of the cadherin family that lacks the HisAlaVal motif and is anchored to the membrane through a glycosyl phosphatidylinositol moiety (Ranscht, B., and M. T. Dours-Zimmermann. 1991. Neuron. 7:391-402). To assay the function of T-cadherin in cell adhesion, we have transfected T-cadherin cDNA into CHO cells. Two proteins, mature T-cadherin and the uncleaved T-cadherin precursor, were produced from T-cadherin cDNA. The T-cadherin proteins differed from classical cadherins in several aspects. First, the uncleaved T-cadherin precursor was expressed, together with mature T-cadherin, on the surface of the transfected cells. Second, in the absence of calcium, T-cadherin was more resistant to proteolytic cleavage than other cadherins. Lastly, in contrast to classical cadherins, T-cadherin was not concentrated into cell-cell contacts between transfected cells in monolayer cultures. In cellular aggregation assays, T-cadherin induced calcium-dependent, homophilic adhesion which was abolished by treatment of T-cadherin-transfected cells with phosphatidylinositol-specific phospholipase C. These results demonstrate that T-cadherin is a functional cadherin that differs in several properties from classical cadherins. The function of T-cadherin in homophilic cell recognition implies that the mechanism of T-cadherin-induced adhesion is distinct from that of classical cadherins. RP VESTAL, DJ (reprint author), NCI,LA JOLLA CANC RES FDN,LA JOLLA,CA 92037, USA. FU NCI NIH HHS [CA09579-04]; NICHD NIH HHS [HD25938] NR 56 TC 123 Z9 132 U1 0 U2 3 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 OCT PY 1992 VL 119 IS 2 BP 451 EP 461 DI 10.1083/jcb.119.2.451 PG 11 WC Cell Biology SC Cell Biology GA JT981 UT WOS:A1992JT98100018 PM 1400585 ER PT J AU BOGNER, P SKEHAN, P KENNEY, S SAINZ, E AKESON, MA FRIEDMAN, SJ AF BOGNER, P SKEHAN, P KENNEY, S SAINZ, E AKESON, MA FRIEDMAN, SJ TI STABILIZATION OF INTERCELLULAR CONTACTS IN MDCK CELLS DURING CA-2+ DEPRIVATION - SELECTIVE EFFECTS OF MONOCARBOXYLIC ACIDS ON DESMOSOMES SO JOURNAL OF CELL SCIENCE LA English DT Article DE MDCK CELLS; CELL-CELL ADHESION; CHELATORS; MONOCARBOXYLIC ACIDS; DESMOSOMES ID KIDNEY EPITHELIAL-CELLS; ADHESION MOLECULE UVOMORULIN; POLARIZED EPITHELIUM; OCCLUDING JUNCTIONS; ADHERENS JUNCTIONS; COMPONENTS; TRANSPORT; CULTURE; PROTEIN; PH AB Short-chain monocarboxylic acids (MCAs) selectively protect desmosomal junctions of MDCK cells from disruption by chelating agents and low calcium medium. This effect occurs in the millimolar concentration range and increases inversely with carbon chain length (formate > acetate = propionate > butyrate > isobutyrate > isovalerate). The relative activity of MCAs does not correlate with their overall hydrophobicity or ability to chelate ions, or their effectiveness in lowering cytosolic pH. It exhibits chemical specificity and is dependent upon postconfluency culture age. MCAs also inhibit cell rounding produced by low concentrations of aminocarboxylate-chelating agents. Their effect on cell rounding, but not on desmosomes, can be antagonized by okadaic acid. The possibility is discussed that MCAs may produce their effects by binding specifically to protein(s) associated with the desmosome of mature, fully polarized MDCK monolayers. C1 NCI,BIOL CHEM LAB,BETHESDA,MD 20892. NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21701. NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. PRI DYN CORP,FREDERICK CANC RES FACIL,FREDERICK,MD. NR 54 TC 4 Z9 4 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT PY 1992 VL 103 BP 463 EP 473 PN 2 PG 11 WC Cell Biology SC Cell Biology GA JY116 UT WOS:A1992JY11600018 PM 1478948 ER PT J AU PASTOR, RW SZABO, A AF PASTOR, RW SZABO, A TI LANGEVIN DYNAMICS OF A LINEAR ROTOR IN A MAIER-SAUPE POTENTIAL - KRAMERS TURNOVER OF THE FLIPPING RATE SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID COMPUTER-SIMULATION AB The frictional dependence of the flipping rate of a linear rotor in a Maier-Saupe potential is evaluated from Langevin dynamics simulations. By assuming that the azimuthal angular velocity is rapidly thermalized, an approximate analytic expression for the rate is obtained within the framework of the Mel'nikov-Meshkov treatment of the Kramers turnover problem for one-dimensional bistable potentials. The predictions of this expression are in good agreement with the accurate simulation results. C1 NIDDKO,CHEM PHYS LAB,BETHESDA,MD 20892. RP PASTOR, RW (reprint author), US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012 NR 21 TC 12 Z9 12 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 OCT 1 PY 1992 VL 97 IS 7 BP 5098 EP 5100 DI 10.1063/1.463830 PG 3 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA JR338 UT WOS:A1992JR33800053 ER PT J AU BAGCHI, B CHANDRA, A AF BAGCHI, B CHANDRA, A TI ULTRAFAST SOLVATION DYNAMICS - MOLECULAR EXPLANATION OF COMPUTER-SIMULATION RESULTS IN A SIMPLE DIPOLAR SOLVENT SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID SIMPLE LIQUIDS; ACETONITRILE; MODEL; ION AB Recently Perera and Berkowitz [J. Chem Phys. 96, 3092 (1992)] and Neria and Nitzan [J. Chem. Phys. 96, 5433 (1992)] carried out computer simulations of solvation dynamics of an ion in dense Stockmayer liquids. Both the simulations observed an ultrafast component which decays in a few tens of femtoseconds with a Gaussian time dependence. This is followed by a slow exponential-like decay with a time constant of a few picoseconds. It is shown here that many of the simulation results can be explained very well from a first principles theory with no adjustable parameter. C1 UNIV BRITISH COLUMBIA,DEPT CHEM,VANCOUVER V6T 1Z1,BC,CANADA. INDIAN INST SCI,SSCU,BANGALORE 560012,KARNATAKA,INDIA. RP BAGCHI, B (reprint author), NIDDKO,CHEM PHYS LAB,BETHESDA,MD 20892, USA. OI BAGCHI, BIMAN/0000-0002-7146-5994 NR 19 TC 56 Z9 56 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 OCT 1 PY 1992 VL 97 IS 7 BP 5126 EP 5131 DI 10.1063/1.463809 PG 6 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA JR338 UT WOS:A1992JR33800058 ER PT J AU ORENTREICH, N BRIND, JL VOGELMAN, JH ANDRES, R BALDWIN, H AF ORENTREICH, N BRIND, JL VOGELMAN, JH ANDRES, R BALDWIN, H TI LONG-TERM LONGITUDINAL MEASUREMENTS OF PLASMA DEHYDROEPIANDROSTERONE SULFATE IN NORMAL MEN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ANDROGENS; WOMEN AB Dehydroepiandrosterone sulfate (DS) was measured by direct tritium RIA in longitudinal plasma specimens from 97 normal healthy male participants in the Baltimore Longitudinal Study of Aging. Fasting blood was collected at regular visits (approximately 1.5 yr apart) over an average 13 yr of adulthood (cumulative age range: 32-83 yr). DS was measured in 3-4 widely spaced specimens from each subject. A decline in DS was found in 65 (67%) subjects, 13 subjects (13%) showed no change, and increases were found in the 19 remaining subjects during the study period. A plot of individual data points revealed the same pattern we had obtained previously from a cross-sectional study of a different normal male population. A plot of DS values vs. age among subjects whose DS increased during the study also revealed an age-related decline. Thus, the longitudinal decrease in circulating DS, long inferred from cross-sectional data, is confirmed for normal men in the present study. A more detailed study of every specimen collected during the study period from 12 of the Baltimore Longitudinal Study of Aging subjects (4 whose values tended to be low, 4 whose values tended to be high, and 4 whose values were near the mean) failed to reveal any patterns of variation that could be correlated with changes in life circumstances, health status, or any other discernible factors. Hence, the wide variability seen in DS among individuals within normal populations remains unexplained. C1 ORENTREICH FDN ADVANCEMENT SCI INC, RD 2 BOX 375, COLD SPRING, NY 10516 USA. CUNY BERNARD M BARUCH COLL, DEPT NAT SCI, NEW YORK, NY 10010 USA. FRANCIS SCOTT KEY MED CTR, NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. NR 11 TC 328 Z9 334 U1 1 U2 3 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 OCT PY 1992 VL 75 IS 4 BP 1002 EP 1004 DI 10.1210/jc.75.4.1002 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT815 UT WOS:A1992JT81500006 PM 1400863 ER PT J AU MIXSON, AJ PARRILLA, R RANSOM, SC WIGGS, EA MCCLASKEY, JH HAUSER, P WEINTRAUB, BD AF MIXSON, AJ PARRILLA, R RANSOM, SC WIGGS, EA MCCLASKEY, JH HAUSER, P WEINTRAUB, BD TI CORRELATIONS OF LANGUAGE ABNORMALITIES WITH LOCALIZATION OF MUTATIONS IN THE BETA-THYROID HORMONE RECEPTOR IN 13 KINDREDS WITH GENERALIZED RESISTANCE TO THYROID-HORMONE - IDENTIFICATION OF 4 NEW MUTATIONS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-ERBA-BETA; LIGAND-BINDING DOMAIN; BASE MUTATION; GENE; RAT; TRIIODOTHYRONINE; PITUITARY; DELETION; PROTEIN; ACID AB Generalized resistance to thyroid hormone is an inherited disease characterized by unresponsiveness of pituitary and peripheral tissues to thyroid hormone. Genetic analysis of several kindreds linked this syndrome to the gene for the beta-form of the thyroid hormone receptor, and this led to the subsequent identification of various mutations in the ligand-binding domain of this receptor. In this region we now have found 4 new point mutations with reduced T3-binding affinities from separate kindreds by direct sequencing of polymerase chain reaction products. Similar to previously studied kindreds, the reduction in T3 binding of these four kindreds ranged from 2.5- to 5-fold, indicating that these are not neutral polymorphisms. Furthermore, the pattern of inheritance of these 4 kindreds is familial in 2, sporadic in 1, and unknown in 1. To date, 20 distinct mutations have been identified, of which 18 are clustered in 2 distinct topographical regions: 11 are within the tau(i)/dimerization subdomains of exon 9, and 7 are within the L2 subdomain of exon 10. The 4 newly identified mutations coupled to the 9 mutations our laboratory has previously identified provide new insights into the clinical aspects of generalized resistance to thyroid hormone. Kindreds with mutations in exon 9 compared with those in exon 10 have significantly more problems in language development, as manifested by articulation problems and/or wide discrepancies in verbal and performance IQs. Interestingly, marked variability in language deficiency as well as other clinical patterns were seen not only between kindreds but also within a kindred. Further identification and clinical correlations of new mutations will continue to enhance our understanding of the structure/function relationships and physiological role of the human thyroid hormone receptor. C1 NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, ROOM 8D14, BLDG 10, BETHESDA, MD 20892 USA. NIMH, BETHESDA, MD 20892 USA. CTR INVEST BIOL, ENDOCRINE PHYSIOL UNIT, E-28006 MADRID, SPAIN. RI Parrilla, Roberto/B-6307-2008 NR 40 TC 59 Z9 59 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 OCT PY 1992 VL 75 IS 4 BP 1039 EP 1045 DI 10.1210/jc.75.4.1039 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT815 UT WOS:A1992JT81500014 PM 1400869 ER PT J AU COON, PJ ROGUS, EM DRINKWATER, D MULLER, DC GOLDBERG, AP AF COON, PJ ROGUS, EM DRINKWATER, D MULLER, DC GOLDBERG, AP TI ROLE OF BODY-FAT DISTRIBUTION IN THE DECLINE IN INSULIN SENSITIVITY AND GLUCOSE-TOLERANCE WITH AGE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DEPENDENT DIABETES-MELLITUS; HEALTHY OLDER MEN; BETA-CELL; CARBOHYDRATE-METABOLISM; RESISTANCE; OBESITY; EXERCISE; SECRETION; INTOLERANCE; KINETICS AB The relationships of body composition and physical fitness [maximal aerobic capacity (VO2Max)] to the decline in insulin sensitivity with age were examined in healthy older (47-73 yr; n = 36) and young (19-36 yr; n = 13) men. In 18 older men with normal glucose tolerance (OGTT), glucose disposal rates (M) during hyperinsulinemic euglycemic clamps correlated negatively with the waist to hip ratio (WHR; r = -0.77; P < .001) and percent body fat (r = -0.46; P < 0.05) and positively with VO2max (r = 0.54; P < 0.05), but not with age. Similar relationships existed in the 36 older men with a spectrum of OGTT responses; however, only WHR was independently related to M (r2 = 0.32; P < 0.01). In the older men with normal OGTT, M (mean +/- SEM, 7.88 +/- 0.43 mg/kg fat-free mass-min) was not different from that in the young men (8.56 +/- 0.47; P = NS). Furthermore, in older and young men with normal OGTT matched for WHR, percent fat, or VO2max, glucose disposal was comparable at sequential 15-min intervals during the clamp and in its relationship to insulin concentrations at the tissue level (multicompartmental analysis). In contrast, despite higher steady state plasma insulin levels during the clamp, M was significantly lower in the older men with a higher WHR, greater percent fat, lower VO2max, or impaired OGTT. Thus, in healthy older men up to the age of 73 yr, insulin sensitivity and glucose tolerance are affected primarily by the regional body fat distribution, not age, obesity, or VO2max. C1 FRANCIS SCOTT KEY MED CTR, JOHNS HOPKINS UNIV SCH MED, DEPT MED, DIV GERIATR, BALTIMORE, MD 21224 USA. NIA, GERONTOL RES CTR, METAB SECT, CLIN PHYSIOL LAB, BALTIMORE, MD 21224 USA. FU NCRR NIH HHS [O1-RR-02719]; NIA NIH HHS [KO8-AG00347, P01-AG-04402-05] NR 54 TC 137 Z9 140 U1 1 U2 8 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 OCT PY 1992 VL 75 IS 4 BP 1125 EP 1132 DI 10.1210/jc.75.4.1125 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JT815 UT WOS:A1992JT81500030 PM 1400882 ER PT J AU SCHWARTZ, GJ ZAVILOWITZ, BJ RADICE, AD GARCIAPEREZ, A SANDS, JM AF SCHWARTZ, GJ ZAVILOWITZ, BJ RADICE, AD GARCIAPEREZ, A SANDS, JM TI MATURATION OF ALDOSE REDUCTASE EXPRESSION IN THE NEONATAL RAT INNER MEDULLA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ALDOSE REDUCTASE; DEVELOPMENT; CONCENTRATING MECHANISM; MALATE DEHYDROGENASE; OSMOREGULATION ID ORGANIC OSMOLYTES; RENAL MEDULLA; CELLS; ANTIDIURESIS; ACCUMULATION; DIURESIS; SORBITOL; SEGMENTS; PROTEIN; NACL AB Newborns are less able to concentrate urine than adults are. With development of the concentrating system and a hypertonic medullary interstitium, there is a need to generate intracellular osmolytes such as sorbitol, which is produced in a reaction catalyzed by the enzyme aldose reductase. We sought to discriminate between two possible mechanisms of aldose reductase induction during development: (a) a response to an osmotic stimulus generated by the concentrating mechanism; or (b) part of the genetic program for development of the kidney. We measured the change in aldose reductase mRNA and activity in terminal inner medullary collecting ducts (IMCDs) microdissected from Sprague-Dawley rats during the first month of life. Aldose reductase mRNA was assayed by Northern analysis of total RNA from inner medulla and by detection of the reverse transcription-polymerase chain reaction (RT-PCR) product obtained from single IMCDs using aldose reductase-specific primers. Aldose reductase activity was measured in IMCDs taken from the same rats using a fluorescent microassay. Newborn rat IMCDs had minimal aldose reductase mRNA or activity, however mRNA was readily detected in IMCDs from rats older than 3 d of age, with peak expression occurring at 1-3 wk of age before decreasing to adult levels. In contrast, the mRNA level for a housekeeping metabolic enzyme, malate dehydrogenase, did not change during maturation. Aldose reductase enzyme activity was readily detectable by 6 d of age, peaked at 20 d, then decreased to adult levels. Urine osmolality remained < 600 mosmol/kg until 16 d, then increased to > 1,100 mosmol/kg after 20 d. Thus, aldose reductase mRNA and activity increased before urinary osmolality reached 870 mosmol/kg. Because urine osmolality may not be indicative of inner medullary osmolality and because mother's milk may provide excessive free water to the pups under 3 wk of age, half of the animals in several litters were separated from their mothers for 1 d and inner medullary osmolality, in addition to urine osmolality, was measured by vapor pressure osmometry, while aldose reductase mRNA was assessed densitometrically in IMCDs after RT-PCR. Although fluid restriction resulted in a near doubling of urine osmolality and a tendency towards increased aldose reductase mRNA, there was no consistently significant increase in aldose reductase mRNA or inner medullary osmolality during the first 13 d of life compared to the suckling animals. On the other hand, 2-3-wk-old rats showed significant increases in aldose reductase mRNA, accompanied by increases in inner medullary osmolality, after fluid restriction. Thus, the dissociation between the increases in aldose reductase expression and inner medullary hyperosmolality indicates that the maturational induction of the aldose reductase gene is not a consequence of osmotic stimulation, but rather, part of the developmental program of the kidney. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MOLEC GENET,BRONX,NY 10461. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. EMORY UNIV,SCH MED,DEPT MED,DIV RENAL,ATLANTA,GA 30322. FU NICHD NIH HHS [HD-13232]; NIDDK NIH HHS [R29-DK41707, R01 DK041707] NR 31 TC 41 Z9 41 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1992 VL 90 IS 4 BP 1275 EP 1283 DI 10.1172/JCI115991 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JU681 UT WOS:A1992JU68100015 PM 1401064 ER PT J AU MCELVANEY, NG NAKAMURA, H BIRRER, P HEBERT, CA WONG, WL ALPHONSO, M BAKER, JB CATALANO, MA CRYSTAL, RG AF MCELVANEY, NG NAKAMURA, H BIRRER, P HEBERT, CA WONG, WL ALPHONSO, M BAKER, JB CATALANO, MA CRYSTAL, RG TI MODULATION OF AIRWAY INFLAMMATION IN CYSTIC-FIBROSIS - INVIVO SUPPRESSION OF INTERLEUKIN-8 LEVELS ON THE RESPIRATORY EPITHELIAL SURFACE BY AEROSOLIZATION OF RECOMBINANT SECRETORY LEUKOPROTEASE INHIBITOR SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AEROSOL THERAPY; ANTIPROTEASE; CYTOKINE; NEUTROPHIL CHEMOATTRACTANT; NEUTROPHIL ELASTASE ID LEUKOCYTE PROTEASE INHIBITOR; BRONCHOALVEOLAR LAVAGE; ALPHA-1-PROTEINASE INHIBITOR; PROTEINASE-INHIBITORS; GENE-EXPRESSION; ELASTASE; NEUTROPHILS; IDENTIFICATION; LUNG; DNA AB Based on the knowledge that neutrophil elastase (NE) in cystic fibrosis (CF) epithelial lining fluid (ELF) can induce human bronchial epithelial cells to express the gene for interleukin 8 (IL-8), an 8.5-kD neutrophil chemoattractant, we have evaluated CF ELF for the presence of IL-8, and investigated the ability of aerosolized recombinant secretory leukoprotease inhibitor (rSLPI) to suppress NE, and hence IL-8, levels on the respiratory epithelial surface in CF. Enzyme-linked immunoassay revealed 21.9 +/- 4.8 nM IL-8 in CF ELF compared with none in normals. Active NE was detectable in ELF of all individuals with CF and was significantly decreased (P < 0.03) after aerosolization of rSLPI. Human bronchial epithelial cells exposed to CF ELF recovered before rSLPI therapy expressed IL-8 mRNA transcripts, but ELF recovered after rSLPI therapy induced far less bronchial epithelial cell IL-8 gene expression. Consistent with this, rSLPI aerosol therapy caused a marked reduction in CF ELF IL-8 levels (P < 0.05) and neutrophil number (P < 0.02). There was also a clear association between CF ELF active NE and IL-8 levels (r = 0.94). These data suggest that rSLPI therapy not only suppressed respiratory epithelial NE levels, but also breaks a cycle of inflammation on the CF epithelial surface. C1 SYNERGEN,BOULDER,CO 80301. GENENTECH INC,SAN FRANCISCO,CA 94080. RP MCELVANEY, NG (reprint author), NHLBI,PULM BRANCH,BLDG 10,ROOM 6003,BETHESDA,MD 20892, USA. RI McElvaney, Noel/A-6809-2010 NR 45 TC 227 Z9 231 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1992 VL 90 IS 4 BP 1296 EP 1301 DI 10.1172/JCI115994 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JU681 UT WOS:A1992JU68100018 PM 1357002 ER PT J AU MIKOVITS, JA LOHREY, NC SCHULOF, R COURTLESS, J RUSCETTI, FW AF MIKOVITS, JA LOHREY, NC SCHULOF, R COURTLESS, J RUSCETTI, FW TI ACTIVATION OF INFECTIOUS VIRUS FROM LATENT HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION OF MONOCYTES INVIVO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS-1; LATENCY; MONOCYTES; IMMUNE ACTIVATION ID HUMAN PERIPHERAL-BLOOD; T-CELL ACTIVATION; INDUCED EXPRESSION; HIV-1 INFECTION; LYMPHOCYTES-T; MACROPHAGES; AIDS; AMPLIFICATION; RETROVIRUS; SEROCONVERSION AB Individuals infected with HIV may be asymptomatic for years before progressing to overt AIDS. Since HIV can latently infect monocytoid cell lines, we examined whether HIV latency occurs in monocytes in vivo. Freshly isolated monocytes from asymptomatic seropositive individuals examined before and after culture were positive for HIV DNA, but not RNA, as measured by polymerase chain reaction, showing that HIV latency occurs in monocytes in vivo. Coculture of these latently infected monocytes with Con A-activated T cells from HIV-negative normal donors stimulated 90% of the patients' samples and latently infected THP-1 to produce infectious virus. Neither Con A, resting T cells, nor T cell supernatants induced virus. Plasma membranes from activated T cells stimulated HIV production, suggesting cell contact induces factor(s) in monocytes to overcome latency. Thus, monocytes in AIDS patients harbor latent HIV inducible during an immune response, leading to T cell infection and viral-induced pathology. C1 NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, IMMUNOREGULAT LAB, FREDERICK, MD 21702 USA. DYNCORP INC, PROGRAM RESOURCES, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. GEORGE WASHINGTON UNIV, MED CTR, AIDS CLIN TRIALS UNIT, WASHINGTON, DC 20037 USA. FU NCI NIH HHS [N01-CO-74102] NR 43 TC 65 Z9 67 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 OCT PY 1992 VL 90 IS 4 BP 1486 EP 1491 DI 10.1172/JCI116016 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JU681 UT WOS:A1992JU68100040 PM 1401081 ER PT J AU GORSE, GJ FREY, SE NEWMAN, FK BELSHE, RB CLEMENTS, ML DOLIN, R COREY, L GRAHAM, BS BOLOGNESI, D FAST, P AF GORSE, GJ FREY, SE NEWMAN, FK BELSHE, RB CLEMENTS, ML DOLIN, R COREY, L GRAHAM, BS BOLOGNESI, D FAST, P TI DETECTION OF BINDING-ANTIBODIES TO NATIVE AND RECOMBINANT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEINS FOLLOWING RECOMBINANT GP160 IMMUNIZATION MEASURED BY FLOW-CYTOMETRY AND ENZYME IMMUNOASSAYS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HTLV-III; NUCLEOTIDE-SEQUENCE; AIDS VIRUS; IDENTIFICATION; RETROVIRUS; INFECTION; VACCINE; ASSAY; CD4; HIV AB The ability of antibody induced by vaccination with recombinant gp160 (rgp160) to bind to native and recombinant human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins was measured. Thirty-three HIV-1-seronegative healthy adult volunteers were injected four times with 40 or 80 mug of an HIV-1LAV envelope glycoprotein candidate vaccine per dose. The vaccine consisted of rgp160 produced in insect tissue culture cells infected with a recombinant baculovirus which contains the gp160 gene from the HIV-1LAV strain. By using a flow cytometric indirect immunofluorescence assay (FIFA) to detect vaccine-induced antibody to native envelope glycoprotein expressed by target cells infected with HIV-1IIIB, sera from 9 of the 33 vaccinees were positive. These included sera from eight vaccinees which stained HIV-1IIIB-infected cells and sera from two vaccinees which stained target cells infected with HIV-1MN, a heterologous virus strain. None of the sera stained cells infected with the HIV-1RF strain. Envelope glycoprotein-binding antibody was more frequently detectable in an enzyme-linked immunosorbent assay (ELISA) by using rgp160 compared with that which was detectable in the FIFA with uninfected target cells which were pulsed with rgp160 antigen. Positive correlations were observed between the rgp160 FIFA and a whole-virus-lysate enzyme immunoassay, between the rgp160 FIFA and the rgp160 ELISA, and between the rgp160 ELISA and the whole-virus-lysate enzyme immunoassay. The ability of sera from some volunteers who received rgp160 vaccine to bind to HIV-1-infected cells suggests that further studies with this vaccine should be done. C1 ST LOUIS VET AFFAIRS MED CTR,ST LOUIS,MO 63106. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21218. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY 14642. UNIV WASHINGTON,SEATTLE,WA 98195. VANDERBILT UNIV,NASHVILLE,TN 37240. DUKE UNIV,DURHAM,NC 27706. NIAID,BETHESDA,MD 20892. RP GORSE, GJ (reprint author), ST LOUIS UNIV,SCH MED,DIV INFECT DIS & IMMUNOL,ST LOUIS,MO 63104, USA. FU NIAID NIH HHS [N01-AI-05064] NR 23 TC 17 Z9 17 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 OCT PY 1992 VL 30 IS 10 BP 2606 EP 2612 PG 7 WC Microbiology SC Microbiology GA JP653 UT WOS:A1992JP65300015 PM 1400960 ER PT J AU ROSEN, BI PARWANI, AV GORZIGLIA, M LARRALDE, G SAIF, LJ AF ROSEN, BI PARWANI, AV GORZIGLIA, M LARRALDE, G SAIF, LJ TI CHARACTERIZATION OF FULL-LENGTH AND POLYMERASE CHAIN REACTION-DERIVED PARTIAL-LENGTH GOTTFRIED AND OSU GENE-4 PROBES FOR SEROTYPIC DIFFERENTIATION OF PORCINE ROTAVIRUSES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PLAQUE-REDUCTION NEUTRALIZATION; REASSORTMENT OCCURS INVIVO; MONOCLONAL-ANTIBODIES; NUCLEOTIDE-SEQUENCE; ANIMAL ROTAVIRUSES; ANTIGENIC RELATIONSHIPS; STRUCTURAL PROTEINS; RHESUS ROTAVIRUS; NUCLEIC-ACID; VP7 AB To determine the VP4 (P type) specificity of porcine rotaviruses, full- and partial-length gene 4 probes were produced from cloned Gottfried and OSU porcine rotavirus genomic segment 4 cDNAs. The gene 4 segments from the prototype Gottfried (VP7 serotype 4) and OSU (VP7 serotype 5) porcine rotavirus strains were selected for study because of their distinct P types and the occurrence of rotaviruses with similar serotypes among swine. Partial-length gene 4 cDNAs were produced and amplified by the polymerase chain reaction (PCR) and encompassed portions of the variable region (nucleotides 211 to 612) of VP8 encoded by genomic segment 4. The hybridization stringency conditions necessary for optimal probe specificity and sensitivity were determined by dot or Northern (RNA) blot hybridizations against a diverse group of human and animal rotaviruses of heterologous group A serotypes and against representative group B and C porcine rotaviruses. The PCR-derived gene 4 probes were more specific than the full-length gene 4 probes but demonstrated equivalent sensitivity. The Gottfried PCR-derived probe hybridized with Gottfried, SB2, SB3, and SB5 G serotype 4 porcine rotaviruses. The OSU PCR-derived probe hybridized with OSU, EE, A580, and SB-1A porcine rotaviruses and equine Hl rotavirus. Results of the hybridization reactions of the PCR-derived gene 4 probes with selected porcine rotavirus strains agreed with previous serological or genetic analyses, indicating their suitability as diagnostic reagents. C1 OHIO STATE UNIV,OHIO AGR RES & DEV CTR,FOOD ANIM HLTH RES PROGRAM,WOOSTER,OH 44691. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 53 TC 10 Z9 11 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 OCT PY 1992 VL 30 IS 10 BP 2644 EP 2652 PG 9 WC Microbiology SC Microbiology GA JP653 UT WOS:A1992JP65300021 PM 1328281 ER PT J AU IHDE, DC TUCKER, MA AF IHDE, DC TUCKER, MA TI 2ND PRIMARY MALIGNANCIES IN SMALL-CELL LUNG-CANCER - A MAJOR CONSEQUENCE OF MODEST SUCCESS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ACUTE NONLYMPHOCYTIC LEUKEMIA; HODGKINS-DISEASE; CARCINOMA; CHEMOTHERAPY; RESECTION; MORTALITY; THERAPY; TUMORS; TRIAL RP IHDE, DC (reprint author), NCI,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 30 TC 21 Z9 21 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 OCT PY 1992 VL 10 IS 10 BP 1511 EP 1513 PG 3 WC Oncology SC Oncology GA JQ719 UT WOS:A1992JQ71900002 PM 1328546 ER PT J AU SANDA, MG YANG, JC TOPALIAN, SL GROVES, ES CHILDS, A BELFORT, R DESMET, MD SCHWARTZENTRUBER, DJ WHITE, DE LOTZE, MT ROSENBERG, SA AF SANDA, MG YANG, JC TOPALIAN, SL GROVES, ES CHILDS, A BELFORT, R DESMET, MD SCHWARTZENTRUBER, DJ WHITE, DE LOTZE, MT ROSENBERG, SA TI INTRAVENOUS ADMINISTRATION OF RECOMBINANT HUMAN MACROPHAGE COLONY-STIMULATING FACTOR TO PATIENTS WITH METASTATIC CANCER - A PHASE-I STUDY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FACTOR M-CSF; GROWTH-FACTOR; MURINE MACROPHAGES; CELLS; PURIFICATION; INDUCTION; MICE C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. CETUS CORP,EMERYVILLE,CA 94608. NCI,SURG BRANCH,BETHESDA,MD 20892. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015; Belfort Jr, Rubens/E-2252-2012 OI Belfort Jr, Rubens/0000-0002-8422-3898 NR 25 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1992 VL 10 IS 10 BP 1643 EP 1649 PG 7 WC Oncology SC Oncology GA JQ719 UT WOS:A1992JQ71900020 PM 1403042 ER PT J AU LINNOILA, VMI VIRKKUNEN, M AF LINNOILA, VMI VIRKKUNEN, M TI AGGRESSION, SUICIDALITY, AND SEROTONIN SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT SYMP ON BRAIN SEROTONIN AND ITS RELATION TO PSYCHIATRIC DISEASES CY FEB 11, 1992 CL SAN FRANCISCO, CA ID FLUID AMINE METABOLITES; GLUCOSE-TOLERANCE TEST; 5-HYDROXYINDOLEACETIC ACID LEVELS; OBSESSIVE-COMPULSIVE DISORDER; CSF MONOAMINE METABOLITES; IMPULSIVE FIRE SETTERS; CEREBROSPINAL-FLUID; VIOLENT OFFENDERS; FAMILY HISTORY; DEPRESSION AB Studies from several countries, representing diverse cultures, have reported an association between violent suicide attempts by patients with unipolar depression and personality disorders and low concentrations of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). Related investigations have documented a similar inverse correlation between impulsive, externally directed aggressive behavior and CSF 5-HIAA in a subgroup of violent offenders. In these individuals, low CSF 5-HIAA concentrations are also associated with a predisposition to mild hypoglycemia, a history of early-onset alcohol and substance abuse, a family history of type II alcoholism, and disturbances in diurnal activity rhythm. These data are discussed in the context of a proposed model for the pathophysiology of a postulated "low serotonin syndrome." C1 UNIV HELSINKI,DEPT PSYCHIAT,SF-00100 HELSINKI 10,FINLAND. RP LINNOILA, VMI (reprint author), NIAAA,DIV INTRAMURAL CLIN & BIOL RES,BLDG 10,ROOM 3C-103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 55 TC 196 Z9 201 U1 4 U2 12 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 1992 VL 53 SU S BP 46 EP 51 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA JU799 UT WOS:A1992JU79900005 PM 1385390 ER PT J AU BURGUNDER, JM YOUNG, WS AF BURGUNDER, JM YOUNG, WS TI EXPRESSION OF CHOLECYSTOKININ AND SOMATOSTATIN GENES IN THE HUMAN THALAMUS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE INSITU HYBRIDIZATION HISTOCHEMISTRY; CHEMICAL ANATOMY; RETICULAR NUCLEUS; INTRALAMINAR NUCLEI ID INSITU HYBRIDIZATION HISTOCHEMISTRY; NUCLEUS RETICULARIS THALAMI; GAMMA-AMINOBUTYRIC ACID; CENTRAL NERVOUS-SYSTEM; MESSENGER-RNA; RAT-BRAIN; PROJECTION NEURONS; NEUROPEPTIDE CHOLECYSTOKININ; REGIONAL DISTRIBUTION; INTRALAMINAR NUCLEI AB The cholecystokinin (CCK) gene is expressed in thalamocortical and thalamostriatal neurons of the rat. In the cat, this peptide is found in some intralaminar and midline nuclei, whereas somatostatin (SRIF) is expressed in the reticular nucleus of the cat but not in rat. Since the putative neurotransmitters used by thalamic neurons are still incompletely known, especially in humans, we investigated the expression of the CCK and SRIF genes in the human thalamus by using hybridization histochemistry. CCK mRNA was found in many neurons, located in several nuclei of the dorsal thalamus. They were especially numerous and widespread in the nuclei associated with the internal thalamic lamina. They formed a continuum in the basal medial thalamus, from the central-medial nucleus, through the centre, median/parafascicular complex to the limitans and suprageniculate nuclei. In addition, neurons with CCK mRNA were found medially and laterally to the mediodorsal nucleus, in the midline and intralaminar nuclei. Only rare neurons with CCK mRNA were found in other nuclei (e.g., in the ventral group of nuclei). SRIF mRNA was found in many neurons of the reticular nucleus, but not in the dorsal thalamus. Neurochemical features of the human thalamus, for the genes studied here, resemble those found in the cat. SRIF may play a role in modulating dorsal thalamic impulses, which may be conveyed through CCK innervation to the striatum and, partly, to the cortex. C1 UNIV BERN,DEPT NEUROL,NEUROMORPHOL LAB,CH-3000 BERN,SWITZERLAND. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 68 TC 5 Z9 5 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 OCT 1 PY 1992 VL 324 IS 1 BP 14 EP 22 DI 10.1002/cne.903240103 PG 9 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA JN444 UT WOS:A1992JN44400002 PM 1357009 ER PT J AU NICKLAUS, MC MILNE, GWA BURKE, TR AF NICKLAUS, MC MILNE, GWA BURKE, TR TI QSAR OF CONFORMATIONALLY FLEXIBLE MOLECULES - COMPARATIVE MOLECULAR-FIELD ANALYSIS OF PROTEIN-TYROSINE KINASE INHIBITORS SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE COMFA; STYRENE DERIVATIVES; PREDICTION OF BIOACTIVE CONFORMATION ID GROWTH-FACTOR RECEPTOR; ORBITAL ELECTRONEGATIVITY; SIGNAL TRANSDUCTION; DIRECT PREDICTION; ANALYSIS COMFA; CANCER; TRANSFORMATION; VALIDATION; REGRESSION; ERBSTATIN AB Comparative Molecular Field Analysis (CoMFA) has been applied to a study of quantitative structure-activity relationships (QSAR) of conformationally flexible molecules. The relationship between three-dimensional structure and activity of 20 styrene derivatives which inhibit protein-tyrosine kinase was determined. A technique was developed that allows accurate prediction of the inhibitory activity of these molecules and identification in each case of the active conformation. The problem of multiple energetically acceptable conformations was approached in an iterative procedure. Use was made of the varying degrees of symmetry among the molecules. First, CoMFA QSAR models were developed using only those compounds that possess a symmetrical substituent pattern on the phenyl ring. These CoMFA models were then used to select the active conformers of the less symmetrical compounds in the set. Allowing multiple conformers for each compound in the dataset yielded higher crossvalidated r2 values and better predictivity of the QSAR models. Different probe atoms (C+, O-, neutral C) were explored, the O- probe atom exhibiting the highest selectivity in the conformer selection process. RP NICKLAUS, MC (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892, USA. RI Nicklaus, Marc/N-4183-2014; Burke, Terrence/N-2601-2014 NR 43 TC 35 Z9 35 U1 0 U2 0 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD OCT PY 1992 VL 6 IS 5 BP 487 EP 504 DI 10.1007/BF00130399 PG 18 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA JX140 UT WOS:A1992JX14000005 PM 1474396 ER PT J AU KILLEN, JD FORTMANN, SP KRAEMER, HC VARADY, A NEWMAN, B AF KILLEN, JD FORTMANN, SP KRAEMER, HC VARADY, A NEWMAN, B TI WHO WILL RELAPSE - SYMPTOMS OF NICOTINE DEPENDENCE PREDICT LONG-TERM RELAPSE AFTER SMOKING CESSATION SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Note ID TOBACCO AB Results of a prospective examination (N = 618) of factors associated with smoking relapse are reported. At 1-year follow-up, a modified version of the Fagerstrom Tolerance Questionnaire (Dependence Index; DI) and a measure of craving entered the logistic model (odds ratio of 2.7 [p < .00 1]). At Year 2, only the DI entered the model (odds ratio of 2.2 [p < .001]). The ability of signal detection analysis (SDA) to produce clinically useful decision rules was also examined. At Year 1, SDA produced 1 subgroup with a 25% nonrelapse rate and another with a 9% nonrelapse rate (odds ratio of 3.4 [p < .001]). At Year 2, SDA produced 1 subgroup with a nonrelapse rate of 19% and another with a nonrelapse rate of 7% (odds ratio of 3.0 [p < .001]). The use of signal detection methods may help clinicians to identify those at greater or lesser risk of relapse. C1 STANFORD UNIV,MED CTR,SCH MED,STANFORD,CA 94305. RP KILLEN, JD (reprint author), NICHHD,6700 EXECUT BLVD,ROOM 7B05,BETHESDA,MD 20892, USA. FU NCI NIH HHS [5R01 CA38303] NR 11 TC 89 Z9 90 U1 0 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 1992 VL 60 IS 5 BP 797 EP 801 DI 10.1037/0022-006X.60.5.797 PG 5 WC Psychology, Clinical SC Psychology GA JP918 UT WOS:A1992JP91800019 PM 1401396 ER PT J AU VOS, Q HODES, RJ AF VOS, Q HODES, RJ TI IMMUNOGLOBULIN (IG) MU,KAPPA-TRANSGENIC MICE EXPRESS TRANSGENIC IDIOTYPE ON ENDOGENOUSLY REARRANGED IGM AND IGA MOLECULES BY SECRETION OF CHIMERIC MOLECULES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEAVY-CHAIN GENE; ALLELIC EXCLUSION; KAPPA-GENES; B-CELLS; ALLOTYPIC DETERMINANT; MONOCLONAL-ANTIBODIES; LIGHT CHAIN; MOUSE LINE; MU-GENES; REPERTOIRE AB The sera of C57BL/6 mice transgenic for a mu(a) allotype heavy (H) chain and kappa light chain gene contained endogenous nontransgene immunoglobulin (IgM) (mu(b) allotype) and IgA molecules which carried the idiotype expressed by the transgenically encoded IgM (mu(a)) molecule. Serological analysis demonstrated that the presence of the transgenic idiotype on endogenous IgM and IgA was caused by the secretion of chimeric molecules that carried both chains encoded by the mu(a) transgene and products of endogenously rearranged Ig mu(b) or alpha genes. These and other results suggest that allelic exclusion of Ig gene rearrangement in mu, kappa transgenic mice is not absolute, that B cells can secrete Igs composed of more than a single (H) chain type, and that endogenous isotype switching does not result in a complete silencing of transgene expression. RP VOS, Q (reprint author), NCI,INST MOLEC CANC,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 44 TC 11 Z9 11 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1992 VL 176 IS 4 BP 951 EP 961 DI 10.1084/jem.176.4.951 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JP862 UT WOS:A1992JP86200004 PM 1402667 ER PT J AU SEDER, RA PAUL, WE DAVIS, MM FAZEKAS DE ST GROTH, B AF SEDER, RA PAUL, WE DAVIS, MM FAZEKAS DE ST GROTH, B TI THE PRESENCE OF INTERLEUKIN-4 DURING INVITRO PRIMING DETERMINES THE LYMPHOKINE-PRODUCING POTENTIAL OF CD4+ T-CELLS FROM T-CELL RECEPTOR TRANSGENIC MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MIXED LEUKOCYTE REACTION; STIMULATORY FACTOR-I; SPLENIC NON-B; MONOCLONAL-ANTIBODY; CYTOKINE PRODUCTION; TH2 CLONES; MURINE LEISHMANIASIS; INTERFERON-GAMMA; DENDRITIC CELLS; LYMPHOCYTES-T AB To study the factors that determine whether CD4+ T cells produce interleukin 4 (IL-4) or interferon gamma (IFN-gamma) upon stimulation we used a system allowing naive T cells to be primed in vitro by specific antigen. Dense CD4+ T cells were purified from mice that expressed transgenes encoding a T cell receptor specific for pigeon cytochrome C peptide 88-104 in association with I-E(k). These T cells produced very limited amounts of IL-4 and IFN-gamma upon immediate challenge with 88-104 and antigen-presenting cells (APC). However, after an initial "priming" culture in which they were incubated for 4 d in the presence of 88-104, APC, and 1,000 U/ml IL-4, the T cells acquired the capacity to produce substantial amounts of IL-4 upon rechallenge but made very little IFN-gamma. Cells primed in the absence of IL-4 produced IFN-gamma upon rechallenge but virtually no IL-4. The inhibitory effect of IL-4 on IFN-gamma production did no appear to be mediated by the induction of IL-10 production since IL-10 addition to initial cultures did not suppress priming for IFN-gamma production, nor did anti-IL-10 block the inhibitory effect of IL-4. IFN-gamma itself did not increase priming for IFN-gamma production, nor did anti-IFN-gamma reduce such priming. IFN-gamma did, however, diminish priming for IL-4 production when limiting amounts of IL-4 (100 U/ml) were used in the initial culture. The dominant effect of IL-4 in determining the lymphokine-producing phenotype of primed cells was observed with dendritic cells (DC), activated B cells, and I-E(k)-transfected fibroblasts as APC. However, the different APC did vary in their potency, with DC being superior to activated B cells, which were superior to transfected fibroblasts. C1 NIAID, IMMUNOL LAB, BLDG 10, ROOM 11N311, BETHESDA, MD 20892 USA. STANFORD UNIV, MED CTR, SCH MED, DEPT MED MICROBIOL & IMMUNOL, STANFORD, CA 94305 USA. STANFORD UNIV, MED CTR, SCH MED, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA. NR 46 TC 946 Z9 951 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1992 VL 176 IS 4 BP 1091 EP 1098 DI 10.1084/jem.176.4.1091 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JP862 UT WOS:A1992JP86200018 PM 1328464 ER PT J AU DONAHUE, RE KESSLER, SW BODINE, D MCDONAGH, K DUNBAR, C GOODMAN, S AGRICOLA, B BYRNE, E RAFFELD, M MOEN, R BACHER, J ZSEBO, KM NIENHUIS, AW AF DONAHUE, RE KESSLER, SW BODINE, D MCDONAGH, K DUNBAR, C GOODMAN, S AGRICOLA, B BYRNE, E RAFFELD, M MOEN, R BACHER, J ZSEBO, KM NIENHUIS, AW TI HELPER VIRUS-INDUCED T-CELL LYMPHOMA IN NONHUMAN-PRIMATES AFTER RETROVIRAL MEDIATED GENE-TRANSFER SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; MURINE LEUKEMIA VIRUSES; EXPRESSION; LINE; SAFE; CONSTRUCTION; GENERATION; THERAPY; RAT AB Moloney Murine Leukemia Virus (MoMuLV) causes T cell neoplasms in rodents but is not known to be a pathogen in primates. The core protein and enzyme genes of the MoMuLV genome together with an amphotropic envelope gene are utilized to engineer the cell lines that generate retroviral vectors for use in current human gene therapy applications. We developed a producer clone that generates a very high concentration of retroviral vector particles to optimize conditions for gene insertion into pluripotent hematopoietic stem cells. This producer cell line also generates a much lower concentration of replication-competent virus that arose through recombination. Stem cells from rhesus monkeys were purified by immunoselection with an anti-CD34 antibody, incubated in vitro for 80-86 h in the presence of retroviral vector particles with accompanying replication-competent virus and used to reconstitute recipients whose bone marrow had been ablated by total body irradiation. The retroviral vector genome was detected in circulating cells of five of eight transplant recipients of CD34+ cells and in the circulating cells of two recipients of infected, unfractionated bone marrow mononuclear cells. Three recipients of CD34+ cells had a productive infection with replication-competent virus. Six or seven mo after transplantation, each of these animals developed a rapidly progressive T cell neoplasm involving the thymus, lymph nodes, liver, spleen, and bone marrow. Lymphoma cells contained 10-50 copies of the replication-competent virus, but lacked the retroviral vector genome. We conclude that replication-competent viruses arising from producer cells making retroviral vectors can be pathogenic in primates, which underscores the importance of carefully screening retroviral producer clones used in human trials to exclude contamination with replication-competent virus. C1 NHLBI, CLIN HEMATOL BRANCH, BLDG 10, ROOM 7C-103, BETHESDA, MD 20892 USA. GENET THERAPY INC, GAITHERSBURG, MD 20878 USA. AMGEN INC, THOUSAND OAKS, CA 91320 USA. NIH, NATL CTR RES SERV, VET RESOURCES PROGRAM, BETHESDA, MD 20892 USA. USN, MED RES INST, IMMUNE CELL BIOL PROGRAM, BETHESDA, MD 20814 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NR 43 TC 443 Z9 454 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1992 VL 176 IS 4 BP 1125 EP 1135 DI 10.1084/jem.176.4.1125 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JP862 UT WOS:A1992JP86200022 PM 1383375 ER PT J AU COBB, JP NATANSON, C HOFFMAN, WD LODATO, RF BANKS, S KOEV, CA SOLOMON, MA ELIN, RJ HOSSEINI, JM DANNER, RL AF COBB, JP NATANSON, C HOFFMAN, WD LODATO, RF BANKS, S KOEV, CA SOLOMON, MA ELIN, RJ HOSSEINI, JM DANNER, RL TI N(OMEGA)-AMINO-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE, RAISES VASCULAR-RESISTANCE BUT INCREASES MORTALITY-RATES IN AWAKE CANINES CHALLENGED WITH ENDOTOXIN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID METHYL-L-ARGININE; TUMOR-NECROSIS-FACTOR; HUMAN SEPTIC SHOCK; GRAM-NEGATIVE BACTEREMIA; MONOMETHYL-L-ARGININE; AMINO-L-ARGININE; RELAXING FACTOR; ENDOTHELIAL-CELLS; ESCHERICHIA-COLI; CARDIOVASCULAR DYSFUNCTION AB Inhibitors of nitric oxide synthase (NOS) have been reported to increase mean arterial pressure in animal models of sepsis and recently have been given to patients in septic shock. However, controlled studies to determine the effects of these agents on cardiovascular function and survival in awake animal models of sepsis have not been reported. To examine the therapeutic potential of NOS inhibition in septic shock, we challenged canines with endotoxin (2 or 4 mg/kg i.v.) and treated them with either normal saline or N(omega)-amino-L-arginine (10 or 1 mg/kg/h), the most specific inhibitor available for the isoform of NOS implicated in septic shock. Endotoxemic animals treated with N(omega)-amino-L-arginine (n = 11) had higher systemic and pulmonary vascular resistance indices (SVRI and PVRI, p less-than-or-equal-to 0.033) and decreased heart rates (p = 0.009), cardiac indices (CI, p = 0.01), oxygen delivery indices (p = 0.027), and oxygen consumption indices (p = 0.046) compared with controls (n = 6). Moreover, N(omega)-amino-L-arginine increased mortality rates after endotoxin challenge (10 of 11 vs. 1 of 6 controls, p = 0.005). Administration of L-arginine did not improve survival or alter the cardiopulmonary effects of N(omega)-amino-L-arginine, which suggests that inhibition of NOS may not hane been competitive. In normal animals, N(omega)-amino-L-arginine alone (n = 3) increased SVRI (p = 0.0008) and mean arterial pressure (p = 0.016), and decreased CI (p = 0.01) compared with saline-treated controls (n = 3), but, at the high dose, also produced neuromuscular rigidity and seizure-like activity that was not apparent in the endotoxemic model. Thus, the mortality rate from endotoxemia increased either because of NOS inhibition per se or because of properties unique to N(omega)-amino-L-arginine. or both. C1 NIH, WARREN G MAGNUSEN CLIN CTR, DEPT CLIN PATHOL, BETHESDA, MD 20892 USA. UNIV TEXAS, HLTH SCI CTR, DIV PULM & CRIT CARE MED, HOUSTON, TX 77225 USA. RP COBB, JP (reprint author), NIH, WARREN G MAGNUSEN CLIN CTR, DEPT CRIT CARE MED, BLDG 10, ROOM 7D-43, BETHESDA, MD 20892 USA. NR 50 TC 236 Z9 244 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1992 VL 176 IS 4 BP 1175 EP 1182 DI 10.1084/jem.176.4.1175 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JP862 UT WOS:A1992JP86200026 PM 1383377 ER PT J AU KOONIN, EV ILYINA, TV AF KOONIN, EV ILYINA, TV TI GEMINIVIRUS REPLICATION PROTEINS ARE RELATED TO PROKARYOTIC PLASMID ROLLING CIRCLE DNA-REPLICATION INITIATOR PROTEINS SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID ABUTILON MOSAIC-VIRUS; SINGLE-STRANDED-DNA; SEQUENCE; PLANTS; FEATURES; PLASTIDS AB It is demonstrated, by means of computer-assisted analysis, that C1 protein involved in the replication of geminivirus DNA is related to the rolling circle replication initiator proteins of eubacterial plasmids, particularly the plasmids of the pMV158 family. Three sequence motifs conserved in the geminivirus and plasmid replication proteins were delineated, one of them encompassing the Tyr residue that presumably forms a covalent linkage to DNA. These findings are compatible with the results of recent analyses of geminivirus replicative intermediates suggesting a rolling circle mechanism for geminivirus DNA replication. It is hypothesized that C1 protein initiates the rolling circle replication of geminivirus DNA replication. It is hypothesized that C1 protein initiates the rolling circle replication of geminivirus DNA by nicking a specific site in the virus-sense DNA and covalently linking to the 5' side of the nick. The putative rolling circle replication initiator domain comprises the N-terminal portion of C1, whereas its C-terminal part is a putative helicase domain. By analogy with prokaryotic systems, it is speculated that the replication initiator domain and the helicase domain function coordinately. The possibility of the origin of geminiviruses from prokaryotic circular ssDNA replicons is discussed. C1 NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. RP KOONIN, EV (reprint author), ACAD SCI USSR,INST MICROBIOL,MOSCOW 117811,USSR. NR 27 TC 114 Z9 115 U1 1 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD OCT PY 1992 VL 73 BP 2763 EP 2766 DI 10.1099/0022-1317-73-10-2763 PN 10 PG 4 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA JT944 UT WOS:A1992JT94400036 PM 1402808 ER PT J AU HATHCOCK, KS HIRANO, H MURAKAMI, S HODES, RJ AF HATHCOCK, KS HIRANO, H MURAKAMI, S HODES, RJ TI CD45 EXPRESSION BY B-CELLS - EXPRESSION OF DIFFERENT CD45 ISOFORMS BY SUBPOPULATIONS OF ACTIVATED B-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; MOLECULAR-WEIGHT ISOFORMS; MURINE LYMPHOCYTE-B; T-CELLS; MONOCLONAL-ANTIBODY; SIGNAL TRANSDUCTION; INTERLEUKIN-5 IL-5; T200; IDENTIFICATION; PHOSPHATASE AB To determine the effect of distinct activation stimuli on CD45 expression by B cells, we have examined the expression of CD45 molecules on murine B cells stimulated with LPS or the Th cell cytokine IL-5. Analysis of CD45 by flow cytometry revealed that unstimulated and stimulated B cells expressed homogeneous amounts of total CD45 but that stimulation with IL-5 resulted in a CD44hi, hyaluronate-adherent subpopulation of activated B cells that expressed a markedly altered pattern of expression of exon-specific CD45R or B220 determinants. The predominant CD45 immunoprecipitated from either unstimulated or LPS-stimulated B cells was of the high molecular mass form (approximately 220 kDa) usually associated with B cells. In contrast, the CD45 proteins immunoprecipitated from the hyaluronate-adherent subpopulation of IL-5-activated B cells were predominantly lower m.w. forms. PCR analysis of amplified CD45 cDNA also showed distinct expression profiles characteristic of each B cell population. The highest molecular size PCR product, corresponding to expression of all three variably expressed CD45 exons (A, B, and C) was prominent in resting B cells and in LPS-activated B cells but was selectively reduced in hyaluronate-adherent IL-5-activated B cells, where lower molecular size PCR products predominated, corresponding to expression of one or two of the variable exons. In contrast, LPS-activated B cells expressed reduced levels of these one- or two-exon forms. In addition, all B cell populations expressed a lower m.w. PCR product corresponding in size to the product expected when exons A, B, and C are spliced out of CD45 mRNA. Thus, analysis of alternative splicing of CD45 mRNA, as well as cell surface expression of CD45 provides a novel parameter for analysis of B cell activation by different stimuli. RP HATHCOCK, KS (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B17,BETHESDA,MD 20892, USA. NR 50 TC 57 Z9 57 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 OCT 1 PY 1992 VL 149 IS 7 BP 2286 EP 2294 PG 9 WC Immunology SC Immunology GA JP189 UT WOS:A1992JP18900007 PM 1388188 ER PT J AU LYNCH, F SHEVACH, EM AF LYNCH, F SHEVACH, EM TI ACTIVATION REQUIREMENTS OF NEWBORN THYMIC GAMMA-DELTA-T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DENDRITIC EPIDERMAL-CELLS; INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; ANTIGEN RECEPTOR GENES; MONOCLONAL-ANTIBODY; ALPHA-BETA; MURINE THYMOCYTES; LIMITED DIVERSITY; FETAL THYMOCYTES; RECOGNITION; EXPRESSION AB We have analyzed the requirements for the induction of proliferative responses by thymic CD4-CD8-gamma-delta T cells. Enriched populations of CD4-CD8- thymocytes from newborn mice, purified by negative selection with anti-CD4, anti-CD8, and anti-TCR alpha-beta mAbs were found to contain approximately 20% gamma-delta T cells that were p55IL-2R-. When these cells were cultured with a panel of lymphokines (IL-1, -2, -4, and -7), a small response was observed to some of the cytokines tested individually; however, combinations of certain lymphokines (IL-1+2, IL-1+7, and IL-2+7) were found to induce significant proliferation and the selective outgrowth (75-90%) of gamma-delta T cells. These cells were IL-2R+, remained CD4-, yet expressed variable levels of CD8. A limited analysis with specific anti-V-gamma and V-delta mAb suggested that there had not been a selective expansion of preexisting V-gamma-2, V-gamma-3, or V-delta-4 populations in response to the stimulatory lymphokine combinations. Thymic CD4-CD8- gamma-delta T cells were unresponsive to stimulation with immobilized anti-pan gamma-delta mAb alone. However, in the presence of immobilized anti-pan gamma-delta mAb and IL-1, IL-2 or IL-7, but not IL-4, a vigorous proliferative response was observed. Phenotypic analysis showed that 80 to 95% of the proliferating cells were polyclonally expanded gamma-delta T cells, expressed the p55IL-2R, and the majority remained CD4-CD8-. Blocking studies with anti-IL-2R mAb showed that stimulation with anti-pan gamma-delta +IL-1, but not anti-pan gamma-delta + IL-7 was dependent on endogenously produced IL-2. Collectively, these studies suggest that the activation requirements of newborn thymic gamma-delta T cells differ markedly from alpha-beta T cells in that gamma-delta T cells 1) respond to combinations of cytokines in the absence of TCR cross-linking, 2) can respond to TCR cross-linking in the presence of exogenous cytokines, 3) but are unable to activate endogenous cytokine production solely in the presence of TCR cross-linking. C1 NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N315,BETHESDA,MD 20892. NR 55 TC 22 Z9 22 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1992 VL 149 IS 7 BP 2307 EP 2314 PG 8 WC Immunology SC Immunology GA JP189 UT WOS:A1992JP18900010 PM 1388190 ER PT J AU ALBER, G KENT, UM METZGER, H AF ALBER, G KENT, UM METZGER, H TI FUNCTIONAL COMPARISON OF FC-EPSILON-RI, FC-GAMMA-RII, AND FC-GAMMA-RIII IN MAST-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; HIGH-AFFINITY RECEPTOR; IMMUNOGLOBULIN-E; BETA-SUBUNIT; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; TRANSFECTED CELLS; ALPHA-SUBUNIT; IGE RECEPTORS; T-CELL AB The cellular responses initiated by cross-linking rodent Fc-gamma-RII-b1, Fc-gamma-RII-b2, Fc-gamma-RIII, and Fc-epsilon-RI in mast cells were compared. Individual murine Fc-gamma-R isoforms were transfected into rat basophilic leukemia cells and after cross-linking the FcR, changes in the phosphorylation of protein tyrosines, in the level of intracellular Ca2+, in the hydrolysis of phosphoinositides, and in the release of arachidonic acid metabolites and hexosaminidase were monitored. Cross-linking of Fc-gamma-RIII initiated all of these early and late biochemical functions, and although they were quantitatively somewhat smaller, the responses were qualitatively indistinguishable from those stimulated by the endogenous Fc-epsilon-RI. However, despite ample expression, neither Fc-gamma-RII-b1 nor Fc-gamma-RII-b2 stimulated these functions when cross-linked. The functional differences between Fc-gamma-RII and Fc-gamma-RIII were studied further by assessing the responses to cross-linking of the endogenous Fc-gamma-R (Fc-gamma-RII-b1, Fc-gamma-RII-b2, and Fc-gamma-RIII) on P815 mouse mastocytoma cells that had been transfected with normal or functionally defective Fc-epsilon-RI. Two types of mutant subunits had previously been observed to impair the activity of Fc-epsilon-RI: gamma-chains missing the cytoplasmic domain, and beta-chains missing the COOH-terminal cytoplasmic domain. In both types of transfectants the functional inhibition of the endogenous Fc-gamma-R paralleled that of the transfected Fc-epsilon-RI. These results are consistent with the gamma-subunit being associated with the functions of Fc-gamma-RIII as well as of Fc-epsilon-RI. The functional results also complement the recently reported evidence that Fc-gamma-RIII can interact with Fc-epsilon-RI beta-subunits (J. Exp. Med. 175:447, 1992). RP ALBER, G (reprint author), NIAMS,ARTHRITIS & RHEUMATISM BRANCH,CHEM IMMUNOL SECT,BLDG 10,RM 9N228,BETHESDA,MD 20892, USA. NR 46 TC 65 Z9 65 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 OCT 1 PY 1992 VL 149 IS 7 BP 2428 EP 2436 PG 9 WC Immunology SC Immunology GA JP189 UT WOS:A1992JP18900027 PM 1388191 ER PT J AU GILFILLAN, AM KADOFONG, H WIGGAN, GA HAKIMI, J KENT, U KOCHAN, JP AF GILFILLAN, AM KADOFONG, H WIGGAN, GA HAKIMI, J KENT, U KOCHAN, JP TI CONSERVATION OF SIGNAL TRANSDUCTION MECHANISMS VIA THE HUMAN FC-EPSILON-RI-ALPHA AFTER TRANSFECTION INTO A RAT MAST-CELL LINE, RBL 2H3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR-MEDIATED ACTIVATION; HIGH-AFFINITY RECEPTOR; PROTEIN KINASE-C; IGE RECEPTOR; IMMUNOGLOBULIN-E; PHOSPHOINOSITIDE HYDROLYSIS; HISTAMINE-RELEASE; RBL-2H3 CELLS; BETA-SUBUNIT; BINDING AB The high affinity receptor for IgE (Fc-epsilon-RI) is present on mast cells and basophils, and the aggregation of IgE-occupied receptors by Ag is responsible for the release of allergic mediators. The Fc-epsilon-RI is composed of at least three different subunits, alpha, beta, and gamma, with the alpha-subunit binding IgE. The series of biochemical events linking receptor aggregation to the release of mediators has not been fully delineated. As a step towards understanding these processes, and for the development of functional cell lines, we have transfected the human Fc-epsilon-RI-alpha subunit into the rat/mast cell line RBL 2H3. These human Fc-epsilon-RI-alpha-transfected cell lines have been characterized with respect to the association of the human alpha-subunit with endogenous rat-beta and gamma-subunits and the ability of aggregated Fc-epsilon-RI-alpha subunits to mediate a variety of biochemical events. The signal transduction events monitored include phosphoinositide hydrolysis, Ca2+ mobilization, tyrosine phosphorylation, histamine release, and arachidonic acid metabolism. In all cases, the events mediated by aggregating human Fc-epsilon-RI-alpha subunits were indistinguishable from those produced via the rat Fc-epsilon-RI-alpha. These results demonstrate that the human Fc-epsilon-RI-alpha subunit can functionally substitute for the rat Fc-epsilon-RI alpha-subunit during signal transduction. The availability of this cell line will provide a means of evaluating potential Fc-epsilon-RI antagonists. C1 HOFFMANN LA ROCHE INC,DEPT MOLEC GENET,NUTLEY,NJ 07110. HOFFMANN LA ROCHE INC,DEPT PHARMACOL,NUTLEY,NJ 07110. HOFFMANN LA ROCHE INC,DEPT IMMUNOPHARMACOL,NUTLEY,NJ 07110. NIAMSK,BETHESDA,MD 20892. NR 35 TC 31 Z9 32 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 OCT 1 PY 1992 VL 149 IS 7 BP 2445 EP 2451 PG 7 WC Immunology SC Immunology GA JP189 UT WOS:A1992JP18900029 PM 1382104 ER PT J AU MANTHEY, CL BRANDES, ME PERERA, PY VOGEL, SN AF MANTHEY, CL BRANDES, ME PERERA, PY VOGEL, SN TI TAXOL INCREASES STEADY-STATE LEVELS OF LIPOPOLYSACCHARIDE-INDUCIBLE GENES AND PROTEIN-TYROSINE PHOSPHORYLATION IN MURINE MACROPHAGES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MICROTUBULE-ASSOCIATED PROTEIN-2; NF-KAPPA-B; BACTERIAL LIPOPOLYSACCHARIDE; PERITONEAL-MACROPHAGES; TAXUS-BREVIFOLIA; SWISS 3T3-CELLS; MESSENGER-RNA; KINASE; TRANSCRIPTION AB Taxol, a microtubule stabilizing agent, exhibits promise in the treatment of breast and ovarian tumors. Recently, this novel drug has been shown to activate murine macrophages to express TNF-alpha and to down-regulate TNF-alpha receptors, activities shared by bacterial LPS. Our study sought to determine if taxol could regulate gene expression in murine macrophages and to examine further the ability of taxol to generate an LPS-like signal. Toward this end, the ability of taxol to induce TNF-alpha mRNA and five other genes (IL-1-beta, IP-10, D3, D7, and D8) associated with LPS-activation of macrophages was examined by Northern blot analysis. Taxol alone (1-30-mu-M) induced murine C3H/OuJ macrophages to secrete bioactive TNF-alpha and express increased levels of each of the six genes under investigation. The magnitude and the kinetics of induction of each gene closely resembled that seen with Escherichia coli K235 LPS. Macrophages from LPS-hyporesponsive C3H/Hej mice, however, failed to induce detectably any of the genes in response to taxol, despite being sensitive to the microtubule stabilizing effects of taxol as determined by immunofluorescence microscopy. The gene induction activity of taxol was in marked contrast to an alternative macrophage activator, heat killed Staphylococcus aureus, which induced a distinct gene profile in C3H/OuJ macrophages and which was equally active in C3H/OuJ and C3H/HeJ macrophages. These data are consistent with an ability of taxol to generate an LPS-like signal, possibly through a common signaling intermediate. As a first step toward identifying signal responses shared by taxol and LPS, we have shown that taxol, as shown previously for LPS, rapidly induces the tyrosine, phosphorylation of a 41- and 42-kDa protein. C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. RP MANTHEY, CL (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,BETHESDA,MD 20814, USA. FU NIAID NIH HHS [AI-08451, AI-18797] NR 49 TC 191 Z9 191 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 OCT 1 PY 1992 VL 149 IS 7 BP 2459 EP 2465 PG 7 WC Immunology SC Immunology GA JP189 UT WOS:A1992JP18900031 PM 1356126 ER PT J AU NECKERS, LM ROSOLEN, A WHITESELL, L AF NECKERS, LM ROSOLEN, A WHITESELL, L TI ANTISENSE INHIBITION OF GENE-EXPRESSION - A TOOL FOR STUDYING THE ROLE OF NMYC IN THE GROWTH AND DIFFERENTIATION OF NEUROECTODERM-DERIVED CELLS SO JOURNAL OF IMMUNOTHERAPY LA English DT Article; Proceedings Paper CT KEYSTONE SYMP ON MELANOMA AND BIOLOGY OF THE NEURAL CREST / MEETING ON CYTOKINES IN GROWTH, DEVELOPMENT AND PATHOGENESIS CY FEB 01-08, 1992 CL TAOS, NM SP MONSANTO, SCHERING, WARNER LAMBERT DE N-MYC; NEUROECTODERM; DIFFERENTIATION; ANTISENSE ID HUMAN NEURO-BLASTOMA; N-MYC EXPRESSION; EMBRYONAL CARCINOMA-CELLS; C-MYC; FAMILY GENES; TRANSGENIC MICE; STEM-CELLS; PC12 CELLS; ONCOGENE; LINES AB To understand the role of individual genes in regulating biological processes, one must be able to interfere specifically with either their expression or function. While monoclonal antibodies have proven very useful in studying cell surface proteins, the specific inhibition of intracellular proteins in viable cells is a much more difficult problem. The goal of antisense technology is to develop small oligonucleotides, plasmids, or retroviral vectors that can be introduced easily into viable cells in order to inhibit gene products specifically. In this report, we will describe our use of antisense DNA and RNA to study the role of the NMYC proto-oncogene in neuroectodermal cell growth and differentiation. RP NECKERS, LM (reprint author), NCI,CLIN PHARMACOL BRANCH,TUMOR CELL BIOL SECT,BETHESDA,MD 20892, USA. NR 28 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 1992 VL 12 IS 3 BP 162 EP 166 DI 10.1097/00002371-199210000-00003 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA JP914 UT WOS:A1992JP91400003 PM 1332744 ER PT J AU MULE, JJ JICHA, DL ROSENBERG, SA AF MULE, JJ JICHA, DL ROSENBERG, SA TI THE USE OF CONGENITALLY IMMUNODEFICIENT MICE TO STUDY HUMAN TUMOR-METASTASES AND IMMUNOTHERAPY SO JOURNAL OF IMMUNOTHERAPY LA English DT Article; Proceedings Paper CT KEYSTONE SYMP ON MELANOMA AND BIOLOGY OF THE NEURAL CREST / MEETING ON CYTOKINES IN GROWTH, DEVELOPMENT AND PATHOGENESIS CY FEB 01-08, 1992 CL TAOS, NM SP MONSANTO, SCHERING, WARNER LAMBERT DE CONGENITAL IMMUNODEFICIENCY; SEVERE COMBINED IMMUNODEFICIENCY; TRIPLE IMMUNODEFICIENCY; MOUSE; TUMOR-INFILTRATING LYMPHOCYTES ID SCID MICE; NUDE-MICE; GROWTH; TISSUE; CANCER; MODEL AB Congenitally immunodeficient strains of mice have proven valuable in the development of relevant models to study human tumor biology, metastases, and immunotherapy. Local invasion and extensive multiorgan metastases in athymic mice have been obtained following orthotopic implantation or onplantation of histologically intact fragments of human tumors. In C.B-17 severe combined immunodeficient (SCID) mice or in triple immunodeficient, beige/nude/xid (BNX) mice, the development and spread of inoculated human leukemia/lymphoma and/or melanoma have mimicked, in some cases, those observed in patients. Reports of reconstitution of SCID and BNX mice with human myeloid or lymphoid cells have suggested that these models might be useful for the study of human immune responses to autologous tumors in vivo. The severe immunocompromised status of these mice have also led to evaluations of the therapeutic efficacy of adoptively transferred, tumor-reactive human T cells. In this report, we review the pertinent information currently available on the use of congenitally immunodeficient mice in studies of human cancer biology and treatment. RP MULE, JJ (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B46,BETHESDA,MD 20892, USA. NR 17 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 1992 VL 12 IS 3 BP 196 EP 198 PG 3 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA JP914 UT WOS:A1992JP91400011 PM 1445811 ER PT J AU TOPALIAN, SL HOM, SS KAWAKAMI, Y MANCINI, M SCHWARTZENTRUBER, DJ ZAKUT, R ROSENBERG, SA AF TOPALIAN, SL HOM, SS KAWAKAMI, Y MANCINI, M SCHWARTZENTRUBER, DJ ZAKUT, R ROSENBERG, SA TI RECOGNITION OF SHARED MELANOMA ANTIGENS BY HUMAN TUMOR-INFILTRATING LYMPHOCYTES SO JOURNAL OF IMMUNOTHERAPY LA English DT Article; Proceedings Paper CT KEYSTONE SYMP ON MELANOMA AND BIOLOGY OF THE NEURAL CREST / MEETING ON CYTOKINES IN GROWTH, DEVELOPMENT AND PATHOGENESIS CY FEB 01-08, 1992 CL TAOS, NM SP MONSANTO, SCHERING, WARNER LAMBERT DE MELANOMA; TUMOR-SPECIFIC ANTIGENS; TUMOR-INFILTRATING LYMPHOCYTES ID T-CELL CLONES; RESTRICTION; EXPRESSION AB We have established that melanomas express shared tumor antigens (Ags) that can be recognized by T cells if presented in the context of self-MHC molecules. Tumor-infiltrating lymphocytes (TILs) from six melanoma patients were tested for lysis of large panels of HLA-matched or unmatched targets representing a variety of tissue types. Lysis was specific for allogeneic melanomas sharing at least one HLA-A, -B, or -C Ag with TILs, and demonstrated commonly expressed tumor Ags. Similar findings were obtained when cytokine secretion by TILs was used to indicate specific Ag recognition. Transfection of the HLA-A2.1 gene into HLA-A2 melanoma lines conferred susceptibility to lysis by HLA-A2 restricted melanoma TILs, demonstrating expression of common tumor Ags among patients of diverse HLA types. These findings have important implications for developing broadly applicable cancer immunotherapies such as vaccines. RP TOPALIAN, SL (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 11 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 1992 VL 12 IS 3 BP 203 EP 206 DI 10.1097/00002371-199210000-00013 PG 4 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA JP914 UT WOS:A1992JP91400013 PM 1445813 ER PT J AU CLERICI, M LANDAY, AL KESSLER, HA PHAIR, JP VENZON, DJ HENDRIX, CW LUCEY, DR SHEARER, GM AF CLERICI, M LANDAY, AL KESSLER, HA PHAIR, JP VENZON, DJ HENDRIX, CW LUCEY, DR SHEARER, GM TI RECONSTITUTION OF LONG-TERM T-HELPER CELL-FUNCTION AFTER ZIDOVUDINE THERAPY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HIV; MEN; 3'-AZIDO-3'-DEOXYTHYMIDINE; DISEASE; NUMBERS; TYPE-1; COUNTS; TRIAL; AIDS AB Peripheral blood mononuclear cells from 12 asymptomatic patients infected with human immunodeficiency virus (HIV) and 4 patients with AIDS were analyzed before and during therapy with zidovudine for T helper cell (Th) function. Th function improved by more than fourfold to one or more of three stimuli tested in 9 (75%) of 12 asymptomatic patients on zidovudine therapy and in 3 of 4 patients with AIDS. Only 6 (7.4%) of 80 untreated HIV-infected control patients showed spontaneous improvement in Th function (P < 10(-6)). Improved Th function was detected as early as 5 weeks into therapy in 6 patients and continued to be evident for > 1 year after start of therapy in 6 patients and for > 2 years in 2 patients. No correlation was observed between improved Th function and changes in CD4+ or CD8+ cell numbers or in levels of serum HIV p24 antigen or beta2-microglobulin. These results suggest inclusion of in vitro Th function as a useful marker in determining the efficacy of antiretroviral drug therapy of HIV-infected patients. C1 NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT MED,CHICAGO,IL 60612. NORTHWESTERN UNIV,SCH MED,DEPT MED,CHICAGO,IL 60611. WILFORD HALL USAF MED CTR,HIV UNIT,LACKLAND AFB,TX 78236. RP CLERICI, M (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008; Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 24 TC 42 Z9 42 U1 0 U2 1 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 OCT PY 1992 VL 166 IS 4 BP 723 EP 730 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JP645 UT WOS:A1992JP64500005 PM 1388195 ER PT J AU HSU, KHL LUBECK, MD DAVIS, AR BHAT, RA SELLING, BH BHAT, BM MIZUTANI, S MURPHY, BR COLLINS, PL CHANOCK, RM HUNG, PP AF HSU, KHL LUBECK, MD DAVIS, AR BHAT, RA SELLING, BH BHAT, BM MIZUTANI, S MURPHY, BR COLLINS, PL CHANOCK, RM HUNG, PP TI IMMUNOGENICITY OF RECOMBINANT ADENOVIRUS-RESPIRATORY SYNCYTIAL VIRUS-VACCINES WITH ADENOVIRUS TYPE-4, TYPE-5, AND TYPE-7 VECTORS IN DOGS AND A CHIMPANZEE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SURFACE-ANTIGEN; COTTON RATS; ANTIBODY-RESPONSE; F-GLYCOPROTEIN; EXPRESSION; DISEASE; LIVE; INFECTION; CHILDREN; INFANTS AB Recombinant adenovirus type 4, 5, and 7 expressing the fusion glycoprotein (F) gene, the attachment glycoprotein (G) gene, or both F and G genes of respiratory syncytial virus (RSV) was constructed. Intratracheal immunization of dogs with Ad7F induced moderate titers of RSV-neutralizing antibodies. After booster immunization with Ad4F, the dogs developed high titers of RSV-specific antibody. Subsequently, three two-dose vaccination regimens, Ad4F/Ad5F, Ad7G/Ad4G, and Ad7FG/Ad4FG, were compared with Ad7F/Ad4F for immunogenicity and protective efficacy. The results indicated that Ad4F/Ad5F was equal or greater in immunogenicity to Ad7F/Ad4F, but Ad7G/Ad4G and Ad7FG/Ad4FG were less effective than Ad7F/Ad4F in inducing RSV-neutralizing antibody. All vaccination regimens completely protected the lungs of dogs from RSV infection. A chimpanzee was sequentially immunized orally with Ad7F, Ad4F, and Ad5F. A low-level antibody response to RSV was induced after the primary immunization, but no significant increases were observed after booster immunizations. C1 NIH,INFECT DIS LAB,BETHESDA,MD 20892. RP HSU, KHL (reprint author), WYETH AYERST RES,DIV BIOTECHNOL & MICROBIOL,POB 8299,PHILADELPHIA,PA 19101, USA. NR 37 TC 50 Z9 54 U1 4 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 OCT PY 1992 VL 166 IS 4 BP 769 EP 775 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JP645 UT WOS:A1992JP64500011 PM 1527411 ER PT J AU BUCANA, CD MUNN, CG SONG, MJ DUNNER, K KRIPKE, ML AF BUCANA, CD MUNN, CG SONG, MJ DUNNER, K KRIPKE, ML TI INTERNALIZATION OF IA-MOLECULES INTO BIRBECK GRANULE-LIKE STRUCTURES IN MURINE DENDRITIC CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID EPIDERMAL LANGERHANS CELLS; LYMPH-NODES; ANTIGEN PRESENTATION; SKIN; ENDOCYTOSIS; MICE; LOCALIZATION; FLOW AB Dendritic cells isolated from the draining lymph nodes of mice sensitized epicutaneously with hapten are potent antigen-presenting cells and contain Birbeck granules and cored tubules characteristic of antigen-activated epidermal Langerhans cells. We used immunogold labeling and transmission electron microscopy to follow the internalization of Ia molecules in these antigen-presenting cells. We found that Ia molecules were internalized into Birbeck granule-like structures in the antigen-activated dendritic cells. Computer reconstruction of serial sections of the dendritic cells demonstrated that these structures span the cytoplasm from the cell membrane to the nuclear membrane and are associated with lysosomes. The internalization of Ia molecules into these structures supports the hypothesis that the Birbeck granule - like structures are derived from the cell membrane and are involved in the antigen-processing/presenting function of the dendritic cells. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT IMMUNOL,1515 HOLCOMBE BLVD,BOX 178,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CELL BIOL,HOUSTON,TX 77030. NEW YORK STATE DEPT HLTH,BMIRR,NIH BIOTECHNOL RESOURCE,ALBANY,NY 12201. FU NCI NIH HHS [CA16672, CA52457] NR 27 TC 29 Z9 29 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1992 VL 99 IS 4 BP 365 EP 373 DI 10.1111/1523-1747.ep12616079 PG 9 WC Dermatology SC Dermatology GA JR164 UT WOS:A1992JR16400001 PM 1401992 ER PT J AU BAX, A POCHAPSKY, SS AF BAX, A POCHAPSKY, SS TI OPTIMIZED RECORDING OF HETERONUCLEAR MULTIDIMENSIONAL NMR-SPECTRA USING PULSED FIELD GRADIENTS SO JOURNAL OF MAGNETIC RESONANCE LA English DT Note ID SPECTROSCOPY; PHASE; PROTEINS; HMQC; 2D C1 BRUKER INSTRUMENTS INC,BILLERICA,MA 01821. RP BAX, A (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 20 TC 339 Z9 339 U1 1 U2 11 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD OCT 1 PY 1992 VL 99 IS 3 BP 638 EP 643 DI 10.1016/0022-2364(92)90221-R PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA JU677 UT WOS:A1992JU67700020 ER PT J AU DONOVAN, DM SAX, CM KLEMENT, JF LI, X CHEPELINSKY, AB PIATIGORSKY, J AF DONOVAN, DM SAX, CM KLEMENT, JF LI, X CHEPELINSKY, AB PIATIGORSKY, J TI CONSERVATION OF MOUSE ALPHA-A-CRYSTALLIN PROMOTER ACTIVITY IN CHICKEN LENS EPITHELIAL-CELLS SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TISSUE-SPECIFIC EXPRESSION; NF-KAPPA-B; NUCLEAR PROTEINS; TRANSGENIC MICE; REGULATORY SEQUENCE; BINDING-PROTEIN; GENE; ENHANCER; PURIFICATION AB Previous transfection experiments have shown that 162 base pairs (bp) of the 5' flanking sequence of the chicken alpha-A-crystallin gene are required for promoter activity in primary chicken lens epithelial cells (PLE), while only 111 bp of the 5' flanking sequence are needed for activity of the mouse alpha-A-crystallin promoter in transfected chicken PLE cells or in a SV40 T-antigen-transformed transfected mouse lens epithelial cell line (alpha-TN4-1). The effect of site-directed mutations covering positions -111 to -34 of the mouse alpha-A-crystallin promoter fused to the bacterial chloramphenicol acetyltransferase (CAT) gene was compared in transfected chicken PLE cells and mouse alpha-TN4-1 cells; selected mutations were also examined in a nontransformed rabbit lens epithelial cell line (N/N1003A). In general, the same mutations reduced promoter activity in the transfected lens cells from all three species, although differences were noted. The mutations severely affected regions -111/-106 and -69/-40 regions in all the transfected cells examined; by contrast, mutations at positions -105/-99 and -87/-70 had a somewhat greater effect in the chicken PLE than the mouse alpha-TN4-1 cells, while mutations of the -93/-88 sequence reduced expression in the alpha-TN4-1 but not the PLE cells. A partial cDNA with sequence similarity to alpha-A-CRYPB1 of the mouse has been isolated from a chicken lens library; mouse alpha-A-CRYBP1 is a putative transcription factor which binds to the -66/-55 sequence of the mouse alpha-A-crystallin promoter. Thus, despite differences in the molecular mechanisms of expression of the chicken and mouse alpha-A-crystallin gene, the present results indicate numerous similarities in the behavior of the mouse promoter in the transfected lens cells of chicken, mouse, and rabbit. C1 NEI,MOLEC & DEV BIOL LAB,BLDG 6,RM 201,BETHESDA,MD 20892. NR 33 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD OCT PY 1992 VL 35 IS 4 BP 337 EP 345 DI 10.1007/BF00161171 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA JN420 UT WOS:A1992JN42000009 PM 1404419 ER PT J AU FREED, WJ AF FREED, WJ TI PROCEEDINGS OF THE IVTH INTERNATIONAL-SYMPOSIUM ON NEURAL TRANSPLANTATION THE GEORGE-WASHINGTON-UNIVERSITY WASHINGTON, DC JULY 12-16, 1992 - FOREWORD SO JOURNAL OF NEURAL TRANSPLANTATION & PLASTICITY LA English DT Editorial Material RP FREED, WJ (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FREUND PUBLISHING HOUSE PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON, ENGLAND W1R 5FA SN 0792-8483 J9 J NEURAL TRANSP PLAS JI J. Neural Transplant. Plast. PD OCT-DEC PY 1992 VL 3 IS 4 BP 169 EP 170 PG 2 WC Neurosciences; Transplantation SC Neurosciences & Neurology; Transplantation GA LL257 UT WOS:A1992LL25700002 ER PT J AU BABILA, T KLEIN, DC AF BABILA, T KLEIN, DC TI STIMULUS DEPRIVATION INCREASES PINEAL-GS-ALPHA AND G PINEAL-BETA SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE DENERVATION; SUPERSENSITIVITY; G-PROTEINS; PINEAL GLAND; SIGNAL TRANSDUCTION ID PROTEIN KINASE-C; SEROTONIN N-ACETYLTRANSFERASE; RAT PINEALOCYTES; CYCLIC-AMP; CHOLERA-TOXIN; ADRENERGIC-STIMULATION; ADENYLATE-CYCLASE; RECEPTOR; BINDING; INFLUX AB Denervation and other forms of stimulus deprivation cause an increase in the magnitude of subsequent responses, a phenomenon commonly referred to as denervation supersensitivity. This has been well demonstrated with the cyclic AMP response to norepinephrine in the pineal gland. In the present report, we address the question of whether stimulus deprivation alters alpha and beta-subunits of the GTP binding regulatory protein that stimulates adenylyl cyclase activity (G(s)). Stimulus deprivation of the pineal gland was produced by denervation (superior cervical ganglionectomy), decentralization of the superior cervical ganglia, or by exposure of the animal to continuous lighting. All increased both the alpha and beta-subunits of G(s) (G(S-alpha) and G(beta)) by up to fourfold, as estimated using semiquantitative western blot technology. These effects were detectable after 1 day of stimulus deprivation and were sustained for 2 weeks. The stimulatory effects of constant light-induced stimulus deprivation were also apparent by measuring cholera toxin-dependent ADP-ribosylation of G(S-alpha), which revealed a four-fold increase in the amount of labeled substrate. The results of in vivo studies were confirmed with in vitro studies. which demonstrated a spontaneous increase in both G(S-alpha) and G(beta) during 72 h of organ culture. The constant light-induced increases in both G(S-alpha) and G(beta) were prevented by continuous administration of isoproterenol (0.3 mg/kg/day), supporting the suggestion that adrenergic stimulation controls the levels of G(S-alpha) and G(beta). These studies indicate that stimulus deprivation increases both G(S-alpha) and G(beta). It appears that such increases play a central role in generating supersensitivity in the pineal gland and may play a role in supersensitivity in other systems. C1 NICHHD,NEUROENDOCRINOL SECT,DEV NEUROBIOL LAB,BLDG 36,ROOM 4A07,BETHESDA,MD 20892. NR 38 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1992 VL 59 IS 4 BP 1356 EP 1362 DI 10.1111/j.1471-4159.1992.tb08448.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JN513 UT WOS:A1992JN51300021 PM 1402887 ER PT J AU DIENEL, GA CRUZ, NF NAKANISHI, H MELZER, P MOULIS, P SOKOLOFF, L AF DIENEL, GA CRUZ, NF NAKANISHI, H MELZER, P MOULIS, P SOKOLOFF, L TI COMPARISON OF RATES OF LOCAL CEREBRAL GLUCOSE-UTILIZATION DETERMINED WITH DEOXY[1-C-14]GLUCOSE AND DEOXY[6-C-14]GLUCOSE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CEREBRAL GLUCOSE UTILIZATION; PENTOSE PHOSPHATE SHUNT ID PENTOSE-PHOSPHATE PATHWAY; 2-DEOXYGLUCOSE 6-PHOSPHATE; CULTURED ASTROCYTES; DEOXYGLUCOSE METHOD; C-14 DEOXYGLUCOSE; BRAIN; METABOLISM; GLUTATHIONE; TOPOGRAPHY; TRANSPORT AB The activity of the pentose phosphate shunt pathway in brain is thought to be linked to neurotransmitter metabolism, glutathione reduction, and synthetic pathways requiring NADPH. There is currently no method available to assess flux of glucose through the pentose phosphate pathway in localized regions of the brain of conscious animals in vivo. Because metabolites of deoxy[1-C-14]glucose are lost from brain when the experimental period of the deoxy[C-14]glucose method exceeds 45 min, the possibility was considered that the loss reflected activity of this shunt pathway and that this hexose might be used to assay regional pentose phosphate shunt pathway activity in brain. Decarboxylation of deoxy[1-C-14]glucose by brain extracts was detected in vitro, and small quantities of C-14 were recovered in the 6-phosphodeoxygluconate fraction when deoxy[C-14]glucose metabolites were isolated from freeze-blown brains and separated by HPLC. Local rates of glucose utilization determined with deoxy[1-C-14]glucose and deoxy[6-C-14]glucose were, however, similar in 20 brain structures at 45, 60, 90, and 120 min after the pulse, indicating that the rate of loss of (CO2)-C-14 from deoxy[1-C-14]glucose-6-phosphate in normal adult rat brain is too low to permit assay pentose phosphate shunt activity in vivo. Further metabolism of deoxy[1-C-14]glucose-6-phosphate via this pathway does not interfere during routine use of the deoxyglucose method or explain the progressive decrease in calculated metabolic rate when the experimental period exceeds 45 min. RP DIENEL, GA (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,BETHESDA,MD 20892, USA. NR 41 TC 11 Z9 11 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 OCT PY 1992 VL 59 IS 4 BP 1430 EP 1436 DI 10.1111/j.1471-4159.1992.tb08457.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JN513 UT WOS:A1992JN51300030 PM 1402893 ER PT J AU SKOLNICK, P BOJE, K MILLER, R PENNINGTON, M MACCECCHINI, ML AF SKOLNICK, P BOJE, K MILLER, R PENNINGTON, M MACCECCHINI, ML TI NONCOMPETITIVE INHIBITION OF N-METHYL-D-ASPARTATE BY CONANTOXIN-G - EVIDENCE FOR AN ALLOSTERIC INTERACTION AT POLYAMINE SITES SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CONANTOKIN-G; MK-801; POLYAMINES; SPERMINE; SPERMIDINE; GLYCINE; N-METHYL-D-ASPARTATE ID AMINO-ACID RECEPTORS; NMDA RECEPTOR; GAMMA-CARBOXYGLUTAMATE; ANTICONVULSANT MK-801; RECOGNITION SITE; MODULATORY SITE; ANTAGONIST; BINDING; COMPLEX; GLYCINE AB Conantokins T and G are polypeptide toxins present in snails of the genus Conus. These substances were recently reported to act as N-methyl-D-aspartate (NMDA) antagonists. In the present study, we examined the possible mechanisms producing this antagonism. Conantokin-G inhibited spermine- and spermidine-stimulated [H-3]MK-801 binding to extensively washed rat forebrain membranes in a noncompetitive manner with IC50 values of approximately 507 and approximately 946 nM, respectively. In contrast, glutamate-enhanced [H-3]MK-801 binding was unaffected by conantokin-G concentrations of less-than-or-equal-to 20-mu-M. At concentrations greater-than-or-equal-to 5-mu-M, conantokin-G effected a modest, noncompetitive inhibition of glycine-stimulated [H-3]MK-801 binding and also produced a small enhancement of basal [H-3]MK-801 binding. Conantokin-G reduced (IC50 approximately 1.08-mu-M) the NMDA-stimulated accumulation of cyclic GMP in cerebellar granule cell cultures to basal values, but did not affect kainate-mediated increases in cyclic GMP. These findings indicate that conantokin-G acts as a noncompetitive NMDA antagonist through an allosteric inhibition of polyamine responses. The neurochemical profile of this polypeptide is distinct from previously described noncompetitive NMDA antagonists. C1 BACHEM BIOSCI,PHILADELPHIA,PA. RP SKOLNICK, P (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 33 TC 54 Z9 56 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1992 VL 59 IS 4 BP 1516 EP 1521 DI 10.1111/j.1471-4159.1992.tb08468.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JN513 UT WOS:A1992JN51300041 PM 1328523 ER PT J AU YOUNG, WS AF YOUNG, WS TI EXPRESSION OF THE OXYTOCIN AND VASOPRESSIN GENES SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Review DE PARAVENTRICULAR NUCLEUS; SUPRAOPTIC NUCLEUS; PITUITARY; REVIEW ID CORTICOTROPIN-RELEASING-FACTOR; MESSENGER-RIBONUCLEIC-ACID; POLY(A) TAIL LENGTH; HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; INSITU HYBRIDIZATION HISTOCHEMISTRY; RAT SUPRACHIASMATIC NUCLEUS; ANTERIOR-PITUITARY-CELLS; DIABETES-INSIPIDUS; ARGININE-VASOPRESSIN; BRATTLEBORO RATS C1 NIMH,CELL BIOL LAB,BLDG 36-2D10,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 183 TC 37 Z9 37 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD OCT PY 1992 VL 4 IS 5 BP 527 EP 540 DI 10.1111/j.1365-2826.1992.tb00201.x PG 14 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA JQ902 UT WOS:A1992JQ90200002 PM 21554637 ER PT J AU HAUGER, RL AGUILERA, G AF HAUGER, RL AGUILERA, G TI REGULATION OF CORTICOTROPIN-RELEASING HORMONE RECEPTORS AND HYPOTHALAMIC PITUITARY-ADRENAL AXIS RESPONSIVENESS DURING COLD STRESS SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE; COLD STRESS; ADRENOCORTICOTROPIC HORMONE; GLUCOCORTICOIDS; PITUITARY ID FACTOR-LIKE IMMUNOREACTIVITY; FACTOR CRF RECEPTORS; RAT PITUITARY; DIFFERENTIAL REGULATION; MESSENGER-RNA; INTERMEDIATE LOBE; IMMOBILIZATION STRESS; INSITU HYBRIDIZATION; TSH SECRETION; ETHER STRESS AB The relationship between pituitary corticotropin-releasing hormone (CRH) receptor changes and corticotrope responsiveness was studied during chronic cold stress. Exposure of rats to 4-degrees-C caused a gradual increase in plasma adrenocorticotropic hormone (ACTH), reaching 3-fold over the basal levels by 6 h (P < 0.005), followed by a reduction to levels only 1.3-fold over basal by 60 h. Plasma corticosterone was significantly increased after 1 h (P < 0.005) and remained elevated for up to the 60 h cold exposure (P < 0.005). No significant changes in plasma thyroid-stimulating hormone, prolactin, growth hormone or vasopressin were observed at 60 h of cold exposure. CRH receptor concentration in the anterior pituitary was unchanged after 18 or 60 h cold stress, whereas in neurointermediate lobe membranes was markedly elevated. Autoradiographic analysis of pituitary CRH receptors confirmed that the increase in CRH binding was confined to the intermediate pituitary. CRH receptor levels in membranes from two brain areas, frontal cortex and amygdala, were unchanged following 60 h cold stress. The areas under the curve for the plasma ACTH and corticosterone levels following an injection of 10 mug/kg ovine CRH in conscious rats, were of similar magnitude in control and 60 h cold exposed rats. Plasma ACTH responses to ether stress were significantly higher in rats exposed to cold for 60 h than in controls. In the intermediate pituitary, basal beta-endorphin/lipotropin release from isolated intermediate pituitary cells was significantly lower in cold stressed rats, and despite the increase in CRH receptors CRH-stimulated values were not higher than in controls. Following 60 h cold exposure, immunoreactive CRH content was decreased in neurointermediate pituitary extracts, while it was slightly increased in the median eminence. Exposure to ether for 5 min resulted in a significant decrease in immunoreactive CRH in the median eminence of cold stressed rats, but not in the controls. The data show a lack of correlation between changes in CRH receptor levels and responsiveness of the corticotrope in the anterior and intermediate pituitary lobes. This suggests that postreceptor events and interaction of CRH with other regulators of ACTH secretion are more likely to account for the changes in pituitary responsiveness during chronic stress. C1 UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,LA JOLLA,CA 92093. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. VET AFFAIRS MED CTR,SAN DIEGO,CA. NR 40 TC 21 Z9 21 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD OCT PY 1992 VL 4 IS 5 BP 617 EP 624 DI 10.1111/j.1365-2826.1992.tb00211.x PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA JQ902 UT WOS:A1992JQ90200012 PM 21554647 ER PT J AU BRASILNETO, JP PASCUALLEONE, A VALLSSOLE, J COHEN, LG HALLETT, M AF BRASILNETO, JP PASCUALLEONE, A VALLSSOLE, J COHEN, LG HALLETT, M TI FOCAL TRANSCRANIAL MAGNETIC STIMULATION AND RESPONSE BIAS IN A FORCED-CHOICE TASK SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID BRAIN-STIMULATION; MOTOR PROGRAMS AB The effects of transcranial magnetic stimulation were studied on the performance of a warned, forced-choice response time task by normal adults. The task consisted of extension of the index finger in response to the click produced by the discharge of the magnetic coil (go-signal). The subjects were asked to choose the right or left finger only after the go-signal was delivered. Single magnetic stimuli were delivered to the prefrontal or motor area, and in the control situation, away from the head. Magnetic stimulation affected hand preference only when it was delivered to the motor area. With stimulation of this area, subjects more often chose the hand contralateral to the site stimulated with response times that were mainly less than 200 ms. With longer response times (between 200 and 1100 ms), magnetic stimulation had no effect on hand preference regardless of the site stimulated. Stimulation of prefrontal areas yielded results similar to the control situation. These results suggest that response bias in this paradigm is caused by an effect of magnetic stimulation on neural structures within, or closely related to, the motor areas of the brain. Although the response bias was clear and predictable, the subjects were unaware of its existence. It is possible to influence endogenous processes of movement preparation externally without disrupting the conscious perception of volition. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,ROOM 5N226,BETHESDA,MD 20892. RI Pascual-Leone, Alvaro/G-6566-2011 NR 14 TC 60 Z9 61 U1 2 U2 6 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD OCT PY 1992 VL 55 IS 10 BP 964 EP 966 DI 10.1136/jnnp.55.10.964 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA JT954 UT WOS:A1992JT95400022 PM 1431962 ER PT J AU ESKANDAR, EN RICHMOND, BJ OPTICAN, LM AF ESKANDAR, EN RICHMOND, BJ OPTICAN, LM TI ROLE OF INFERIOR TEMPORAL NEURONS IN VISUAL MEMORY .1. TEMPORAL ENCODING OF INFORMATION ABOUT VISUAL IMAGES, RECALLED IMAGES, AND BEHAVIORAL CONTEXT SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TWO-DIMENSIONAL PATTERNS; STATE DEPENDENT ACTIVITY; INFEROTEMPORAL CORTEX; RHESUS-MONKEY; SINGLE UNITS; RECOGNITION MEMORY; ENTORHINAL CORTEX; SHORT-TERM; CONNECTIONS; PRIMATE AB 1. Lesions of the inferior temporal (IT) cortex selectively hamper monkeys in tasks requiring visual memory. A system that recognizes images must be able to encode a current stimulus, recall the code of a previous stimulus, compare the codes of the two stimuli, and make a decision on the basis of the outcome of the comparison. Therefore, IT neurons must be involved in at least one of these processes. To determine the specific role of IT neurons in visual memory, we measured the information conveyed in the neuronal responses about current patterns, recalled patterns, and behavioral context. 2. Two monkeys were trained to perform a sequential matching task using a set of 32 black and white Walsh patterns. In the course of an experiment, each pattern was presented repeatedly in sample, match, and nonmatch behavioral contexts. While the monkeys were performing the task, we recorded the activity of 76 neurons from area TE of IT. The neuronal responses to the stimuli were converted to spike density functions, and the resultant waveforms were quantified using their principal components. The relationships between the responses and the stimuli were studied using analysis of variance and information theory. 3. The analysis of variance was applied to the neuronal response waveforms using the context (sample, match, or nonmatch) and the patterns of the stimuli as independent variables and the spike count or the coefficients of the principal components as the dependent variables. We found that the waveforms of most neurons were significantly modulated by both the pattern and the context of the stimulus presentation. 4. We also analyzed the stimulus-response relationships using information theory. The input codes were based on the pattern and context of the stimuli, and the output codes were based on the spike count or the principal components of the responses. The neuronal response waveforms were found to convey significant amounts of information about both the pattern and context of the stimuli. Transmitted information was greatest when the response of a neuron was interpreted as a message about the combination of pattern and context. Nevertheless, there was information about context independent of pattern and vice versa. 5. We also used information theory to determine whether the neuronal responses to the second, or test, stimulus conveyed information about the pattern of the first, or sample, stimulus. The input codes were based on the patterns of the sample stimuli, and the output codes were based on the responses to the nonmatch test stimuli. We found that the responses to the nonmatch stimuli carried significant amounts of information about the pattern of the previous sample stimuli. Furthermore, two thirds of this information was transmitted in the temporal distribution of the spikes and only one third in their number. 6. Area TE includes neurons in the superior temporal sulcus and the inferior temporal gyrus. On the basis of penetration depth records, we found that neurons in the gyrus appeared to convey more than twice as much information about the patterns of the current stimuli as the neurons in the sulcus. Thus there appears to be a functional subdivision within the anatomically defined area TE. 7. We hypothesize that the role of IT neurons in visual memory tasks is to compare the internal representations of current visual images with the internal representations of recalled images. The companion paper tests a hypothetical neuronal mechanism, based on multiplication of temporally modulated waveforms, for making this comparison. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. RP ESKANDAR, EN (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 62 TC 107 Z9 108 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 1992 VL 68 IS 4 BP 1277 EP 1295 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA JV733 UT WOS:A1992JV73300026 PM 1432084 ER PT J AU ESKANDAR, EN OPTICAN, LM RICHMOND, BJ AF ESKANDAR, EN OPTICAN, LM RICHMOND, BJ TI ROLE OF INFERIOR TEMPORAL NEURONS IN VISUAL MEMORY .2. MULTIPLYING TEMPORAL WAVE-FORMS RELATED TO VISION AND MEMORY SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ADAPTIVE PATTERN-CLASSIFICATION; TWO-DIMENSIONAL PATTERNS; SINGLE UNITS; 2-DIMENSIONAL PATTERNS; EXTENDED APPLICATION; RECOGNITION MEMORY; INFORMATION-THEORY; SHORT-TERM; CORTEX; PRIMATE AB 1. In the companion paper we reported on the activity of neurons in the inferior temporal (IT) cortex during a sequential pattern matching task. In this task a sample stimulus was followed by a test stimulus that was either a match or a nonmatch. Many of the neurons encoded information about the patterns of both current and previous stimuli in the temporal modulation of their responses. 2. A simple information processing model of visual memory can be formed with just four steps: 1) encode the current stimulus; 2) recall the code of a remembered stimulus; 3) compare the two codes; 4) and decide whether they are similar or different. The analysis presented in the first paper suggested that some IT neurons were performing the comparison step of visual memory. 3. We propose that IT neurons participate in the comparison of temporal waveforms related to vision and memory by multiplying them together. This product could form the basis of a crosscorrelation-based comparison. 4. We tested our hypothesis by fitting a simple multiplicative model to data from IT neurons. The model generated waveforms in separate memory and visual channels. The waveforms arising from the two channels were then multiplied on a point by point basis to yield the output waveform. The model was fitted to the actual neuronal data by a gradient descent method to find the best fit waveforms that also had the lowest total energy. 5. The multiplicative model fit the neuronal responses quite well. The multiplicative model made consistently better predictions of the actual response waveforms than did an additive model. Furthermore, the fit was better when the actual relationship between the responses and the sample and test stimuli were preserved than when that relationship was randomized. 6. We infer from the superior fit of the multiplicative model that IT neurons are multiplying temporally modulated waveforms arising from separate visual and memory systems in the comparison step of visual memory. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP ESKANDAR, EN (reprint author), NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892, USA. NR 46 TC 26 Z9 26 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 1992 VL 68 IS 4 BP 1296 EP 1306 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA JV733 UT WOS:A1992JV73300027 PM 1432085 ER PT J AU WOLOZIN, B ZHENG, B LOREN, D LESCH, KP LEBOVICS, RS LIEBERBURG, I SUNDERLAND, T AF WOLOZIN, B ZHENG, B LOREN, D LESCH, KP LEBOVICS, RS LIEBERBURG, I SUNDERLAND, T TI BETA/A4 DOMAIN OF APP - ANTIGENIC DIFFERENCES BETWEEN CELL-LINES SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE AMYLOID; ALZHEIMERS; OLFACTORY; NEUROBLASTS; ELECTROPHORESIS; CELL CULTURE; IMMUNOBLOT ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; MESSENGER-RNA; HUMAN-BRAIN; EXPRESSION; GENE; PHOSPHORYLATION; TISSUES; QUANTITATION AB The expression of amyloid precursor protein (APP) in olfactory neuroblasts has been examined with a panel of antibodies directed against varied regions of the APP molecule. The pattern of reactivity was compared to that in the transformed human glial cell line SVG, human cortical brain tissue, and in kidney epithelial 293 cells containing stably transfected and overexpressed human APP751. Antibodies directed against the C-terminus and extracellular domains of amyloid precursor protein (APP) react more strongly on immunoblot with transfected 293 cells and brain tissue than with olfactory neuroblasts (ON) or SVG cells. Antibodies directed against the beta/A4 region of APP show a contrasting pattern of reactivity, yielding greater reactivity with ON and SVG cells than with transfected 293 cells or brain tissue. Analysis of the APP transcripts using polymerase chain reaction indicates that ON and SVG both make predominantly APP770 and 751, as does the transfected 293 cell line. In the absence of any differences in APP transcripts among the cell lines, the difference in availability of the beta/A4 region appears likely to be due to posttranslational modification. These data therefore indicate that processing of APP varies among cell lines and thus may vary from tissue to tissue. C1 NIDCD,BETHESDA,MD. RP WOLOZIN, B (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 31 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT PY 1992 VL 33 IS 2 BP 189 EP 195 DI 10.1002/jnr.490330202 PG 7 WC Neurosciences SC Neurosciences & Neurology GA JU518 UT WOS:A1992JU51800001 PM 1453487 ER PT J AU LAKSHMANAN, M REYNOLDS, JC DELVECCHIO, S MERINO, MJ NORTON, JA ROBBINS, J AF LAKSHMANAN, M REYNOLDS, JC DELVECCHIO, S MERINO, MJ NORTON, JA ROBBINS, J TI PELVIC RADIOIODINE UPTAKE IN A RECTAL WALL TERATOMA AFTER THYROIDECTOMY FOR PAPILLARY CARCINOMA SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID PRIMARY RETROPERITONEAL TERATOMA; I-131; ADULTS; OVARY AB A 30-yr-old woman with previously resected papillary thyroid carcinoma was found to have a pelvic lesion which concentrated radioiodine. By performing simultaneous I-131 whole-body and Tc-99m-methylene diphosphonate bone scans, we found the lesion to be in soft tissue between the sacrum and bladder. Radioiodine therapy was postponed so that the lesion, a benign teratoma of the rectal wall, could be surgically removed. Prior to laparotomy, the patient received a second tracer dose of I-131 so that the lesion could be located at surgery with a hand-held gamma detector. A postoperative whole-body I-131 scan confirmed that the lesion had been removed, thus reducing the absorbed radiation that would have been received by the ovaries during radioiodine therapy. Although the lesion contained both thyroid and gastric epithelium, accumulated I-131 was limited to the area with thyroid follicles. C1 NIDDKD,CLIN ENDOCRINOL BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. WARREN GRANT MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. FAC MED & CHIRURG NAPLES TWO,IST MED NUCL,NAPLES,ITALY. RI Del Vecchio, Silvana/F-4972-2012; OI DEL VECCHIO, Silvana/0000-0002-5466-1213 NR 28 TC 14 Z9 15 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 1992 VL 33 IS 10 BP 1848 EP 1850 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JU520 UT WOS:A1992JU52000028 PM 1403156 ER PT J AU WEI, Z MCLAUGHLIN, JK GAO, YT GAO, RN BLOT, WJ AF WEI, Z MCLAUGHLIN, JK GAO, YT GAO, RN BLOT, WJ TI OCCUPATIONAL RISKS FOR NASOPHARYNGEAL CANCER IN SHANGHAI SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID NASAL CANCER; SALTED FISH; CARCINOMA; SWEDEN; CHINA AB To investigate occupational determinants of nasopharyngeal cancer (NPC) in the urban area of Shanghai, occupational information for 996 incident NPC patients diagnosed during 1980 to 1984 was compared with 1982 census data on employment. Standardized incidence ratios for NPC were estimated for broad and detailed occupational classifications. For the broadest level of classification, no excess risk was observed among craftmen and related manufacturing workers, but within this group significant excess risks were observed for specific occupations of textile weavers and knitters, metal smelting, converting, and refining furnacemen; boiler firemen; blacksmiths, hammersmiths, and forging-press operators; bakers, pastry cooks, and confectionery makers; welders and flame-cutters; and metal grinders, polishers, tool sharpeners, and machine-tool operators. Some of these findings are new; others are consistent with previous studies in other areas of the world. This study provides further evidence for the role of occupational factors in NPC. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 431,BETHESDA,MD 20892. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. NR 21 TC 0 Z9 0 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD OCT PY 1992 VL 34 IS 10 BP 1004 EP 1007 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JU244 UT WOS:A1992JU24400011 ER PT J AU SUSMAN, EJ DORN, LD FLETCHER, JC AF SUSMAN, EJ DORN, LD FLETCHER, JC TI PARTICIPATION IN BIOMEDICAL-RESEARCH - THE CONSENT PROCESS AS VIEWED BY CHILDREN, ADOLESCENTS, YOUNG-ADULTS, AND PHYSICIANS SO JOURNAL OF PEDIATRICS LA English DT Article ID INFORMED CONSENT; CANCER AB We examined the capacity of children, adolescents, and young adults to assent and consent to participation in biomedical research, and what physician-investigators believe is important for patients in these age groups to know about such participation. The sample included 44 male and female subjects, ranging in age from 7 to 20 years, who were hospitalized to treat either pediatric cancer or obesity. The participants completed a structured interview that assessed knowledge of research participation using the elements outlined in the federal guidelines for informed consent. The study subjects were most knowledgeable about those elements of consent that assessed concrete information (e.g., freedom to ask questions, time elements involved, and the benefits of participation). They were less knowledgeable about those elements of informed consent that assessed abstract information (e.g., scientific vs therapeutic purpose of the study, and alternative treatments). Chronologic age was not related to knowledge of the elements of informed consent. The strategies that the study subjects used to reason about participation in research appeared to parallel their reasoning about other physical phenomena. C1 NIMH, DEV PSYCHOL LAB, BETHESDA, MD 20892 USA. NIH, CTR CLIN, BETHESDA, MD 20892 USA. RP SUSMAN, EJ (reprint author), PENN STATE UNIV, E-314 HLTH & HUMAN DEV BLDG, UNIV PK, PA 16802 USA. FU NINR NIH HHS [SRC-5-F31-NR05965] NR 24 TC 90 Z9 91 U1 1 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 1992 VL 121 IS 4 BP 547 EP 552 DI 10.1016/S0022-3476(05)81142-4 PG 6 WC Pediatrics SC Pediatrics GA JR920 UT WOS:A1992JR92000008 PM 1403387 ER PT J AU HUSSON, RN CHUNG, Y MORDENTI, J BUTLER, KM CHEN, S DULIEGE, AM BROUWERS, P JAROSINSKI, P MUELLER, BU AMMANN, A PIZZO, PA AF HUSSON, RN CHUNG, Y MORDENTI, J BUTLER, KM CHEN, S DULIEGE, AM BROUWERS, P JAROSINSKI, P MUELLER, BU AMMANN, A PIZZO, PA TI PHASE-I STUDY OF CONTINUOUS-INFUSION SOLUBLE CD4 AS A SINGLE AGENT AND IN COMBINATION WITH ORAL DIDEOXYINOSINE THERAPY IN CHILDREN WITH SYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF PEDIATRICS LA English DT Article ID CENTRAL VENOUS CATHETERS; AIDS-RELATED COMPLEX; HIV INFECTION; TYPE-1; RECEPTOR; ANTIGEN; REPLICATION; ZIDOVUDINE; AFFINITY; INVITRO AB To determine the safety and pharmacokinetics of recombinant soluble CD4 (sCD4) administered by continuous intravenous infusion to children with symptomatic human immunodeficiency virus type 1 infection, we conducted a phase I study at the National Cancer Institute. Three dose levels of sCD4 were evaluated: 100, 300, and 1000 mug/kg per day. After an initial 12 weeks of treatment with sCD4 alone, dideoxyinosine at a dose of 90 mg/m2 every 8 hours was added and subjects were observed for an additional 12 weeks. Combination therapy was continued in patients in whom it was well tolerated. In addition to toxicity and pharmacokinetic monitoring, surrogate markers of antiviral activity were evaluated. Eleven children were enrolled in the study. During the 12 weeks of treatment with sCD4 alone, and during subsequent sCD4 plus dideoxyinosine combination therapy, no significant toxic reaction attributable to sCD4 or dideoxyinosine was encountered. Low-level anti-CD4 antibodies developed in two patients. Steady-state sCD4 levels increased proportionately at higher doses. The CD4 cell counts and serum p24 antigen levels did not provide evidence of antiviral activity. We conclude that sCD4 was well tolerated at doses up to 1000 mug/kg per day when administered by continuous intravenous infusion; however, evidence of in vivo antiviral activity was not observed in this study. C1 NCI, PEDIAT BRANCH,BLDG 10,ROOM 13N240, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NIH, CTR CLIN, DEPT PHARM, BETHESDA, MD 20892 USA. GENENTECH INC, SAN FRANCISCO, CA 94080 USA. NR 26 TC 23 Z9 23 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 1992 VL 121 IS 4 BP 627 EP 633 DI 10.1016/S0022-3476(05)81161-8 PG 7 WC Pediatrics SC Pediatrics GA JR920 UT WOS:A1992JR92000025 PM 1357124 ER PT J AU BACH, MA BLUM, DM ROSE, SR CHARNAS, LR AF BACH, MA BLUM, DM ROSE, SR CHARNAS, LR TI MYALGIA AND ELEVATED CREATINE-KINASE ACTIVITY ASSOCIATED WITH SUBCUTANEOUS INJECTIONS OF DILUENT SO JOURNAL OF PEDIATRICS LA English DT Note AB A 16-year-old boy with short stature and mild primary hypothyroidism received subcutaneous injections of either recombinant human growth hormone or placebo in diluent that contained glycerol and m-cresol as a preservative. While he was receiving the study drug, myalgia developed and serum creatine kinase values were elevated. Both resolved when injections were stopped and recurred when injections of diluent alone were given. The myalgia and elevated creatine kinase activity were apparently caused by a component of the diluent. C1 NICHHD, HUMAN GENET BRANCH, BETHESDA, MD 20892 USA. NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT NURSING, BETHESDA, MD 20892 USA. UNIV NEW MEXICO, DEPT PEDIAT, ALBUQUERQUE, NM 87131 USA. RP BACH, MA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 5 TC 10 Z9 10 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 1992 VL 121 IS 4 BP 650 EP 651 DI 10.1016/S0022-3476(05)81165-5 PG 2 WC Pediatrics SC Pediatrics GA JR920 UT WOS:A1992JR92000029 PM 1403405 ER PT J AU DEFIEBRE, NC MARLEY, RJ WEHNER, JM COLLINS, AC AF DEFIEBRE, NC MARLEY, RJ WEHNER, JM COLLINS, AC TI LIPID SOLUBILITY OF SEDATIVE-HYPNOTIC DRUGS INFLUENCES HYPOTHERMIC AND HYPNOTIC RESPONSES OF LONG-SLEEP AND SHORT-SLEEP MICE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SELECTIVELY BRED MICE; DIFFERENTIAL SENSITIVITY; ETHANOL HYPOTHERMIA; INBRED STRAINS; MOUSE LINES; SS MICE; TOLERANCE; LS; ABSORPTION; ALCOHOLS AB The anesthetic potency of many agents, including alcohols, barbiturates and other sedative-hypnotic drugs, is influenced by lipid solubility. Previous studies from our laboratory, however, have demonstrated that genetic factors influence this relationship. We have reported that mouse lines selectively bred for differences in duration of ethanol-induced anesthesia, the long-sleep (LS) and short-sleep (SS) mice, differ in sleep-time response to water-soluble, but not lipid-soluble, sedative-hypnotic drugs. The studies described here sought to determine whether this same relationship exists for the hypothermic response produced by 17 sedative-hypnotic drugs in the LS and SS mice. Dose-response and time course relationships for hypothermic actions were determined and were compared with the dose-related anesthetic effects of the drugs. Hypothermic potencies increased along with lipid solubility for both the LS and SS mouse lines, but the rate of change differed for the two mouse lines. LS mice were more responsive to ethanol and other water-soluble drugs whereas the SS were more responsive to lipid-soluble drugs; significant correlations were obtained between lipid solubility (log P-octanol-water partition coefficient) and relative LS-SS responsiveness to both the hypothermic and hypnotic actions of the 17 test drugs. Thus, both hypnotic and hypothermic actions of sedative-hypnotic drugs are correlated with lipid solubility. Possible explanation for these correlations include greater LS central nervous system sensitivity to water-soluble drugs and LS-SS differences in distribution of lipid-soluble drugs. C1 UNIV COLORADO,SCH PHARM,INST BEHAV GENET,CAMPUS BOX 477,BOULDER,CO 80309. UNIV COLORADO,DEPT PSYCHOL,BOULDER,CO 80309. NIDA,ADDICT RES CTR,BALTIMORE,MD. FU NIAAA NIH HHS [AA-00141, AA-03527]; NIDA NIH HHS [DA-00116] NR 35 TC 11 Z9 11 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1992 VL 263 IS 1 BP 232 EP 240 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JT987 UT WOS:A1992JT98700034 PM 1403788 ER PT J AU MOODY, TW STALEY, J ZIA, F COY, DH JENSEN, RT AF MOODY, TW STALEY, J ZIA, F COY, DH JENSEN, RT TI NEUROMEDIN-B BINDS WITH HIGH-AFFINITY, ELEVATES CYTOSOLIC CALCIUM AND STIMULATES THE GROWTH OF SMALL-CELL LUNG-CANCER CELL-LINES SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GASTRIN-RELEASING PEPTIDE; BOMBESIN-LIKE PEPTIDES; SWISS 3T3 CELLS; SPINAL-CORD; RAT-BRAIN; BIOCHEMICAL-CHARACTERIZATION; RECEPTOR ANTAGONISTS; MOLECULAR-CLONING; ANALOGS FUNCTION; GENE-EXPRESSION AB Previously, gastrin-releasing peptide (GRP) receptors were identified on small-cell lung cancer (SCLC) cells and GRP functioned as a SCLC autocrine growth factor. Here the effects of neuromedin B (NMB) on SCLC cells were investigated. [I-125-Tyr0]NMB bound with high affinity to three of seven SCLC cell lines examined. [I-125-Tyr0]NMB bound to SCLC cell line NCI-H209 and NCI-H345 in a time-dependent and reversible manner. [I-125-Tyr0]NMB bound with high affinity (K(d) = 1 nM) to a single class of sites (B(max) = 800/cell). Specific [I-125-Tyr0]NMB binding was inhibited with high affinity by NMB (IC50 = 1 nM) and moderate affinity by bombesin, GRP and [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P ([APTTL]SP) but not GRP1-16 (IC50 = 50, 100, 1,000 and > 10,000 nM, respectively). In Fura 2 AM loaded NCI-H345 cells, NMB elevated cytosolic calcium in a concentration-dependent manner. N MB (1 0 n M) elevated the cytosolic calcium from 1 50 to 1 80 nM and calcium was released from intracellular pools. The increase in cytosolic calcium caused by 10 nM NMB was reversed by 1 muM [APTTL]SP but not 1 muM [D-Phe6]bombesin6-13methylester, a GRP receptor antagonist. Also, NMB stimulated the clonal growth of NCl-H209 and NCI-H345 in a concentration-dependent manner. The increase in the clonal growth caused by NMB was reversed by 1 muM [APTTL]SP. These data suggest that NMB receptors may regulate the proliferation of some SCLC cells. C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20037. TULANE UNIV,SCH MED,DEPT MED,NEW ORLEANS,LA 70112. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD. FU NCI NIH HHS [CA-53477] NR 33 TC 54 Z9 54 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1992 VL 263 IS 1 BP 311 EP 317 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JT987 UT WOS:A1992JT98700044 PM 1328611 ER PT J AU LICHT, D CRONSTEIN, B DYKES, DC PEDERSEN, J LUSTER, SM TRAMPOTA, M HULL, E FRIEDMAN, FK PINCUS, MR AF LICHT, D CRONSTEIN, B DYKES, DC PEDERSEN, J LUSTER, SM TRAMPOTA, M HULL, E FRIEDMAN, FK PINCUS, MR TI CORRELATION OF THE CONFORMATION OF A MODIFIED RIBONUCLEASE OCTAPEPTIDE, HOMOLOGOUS TO PEPTIDE-T, WITH ITS ABILITY TO INDUCE CD4-DEPENDENT MONOCYTE CHEMOTAXIS SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE RNASE PEPTIDE; PEPTIDE-T; CD4 RECEPTOR; GP120; HIV ID HUMAN IMMUNODEFICIENCY VIRUS; RECEPTOR-BINDING; INFECTIVITY AB Peptide T, from the human immunodeficiency virus (HIV), whose sequence is Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr, has been shown to inhibit attachment of this virus to T cells and neural cells bearing the CD4 receptor. This peptide shares extensive homology with the 19-26 segment of ribonuclease A (RNase A), whose sequence is Ala-Ala-Ser-Ser-Ser-Asn-Tyr-Cys. Based on comparison of the structures of peptides occurring in proteins of known structure that are homologous to peptide T, viz, RNase A and endothiapepsin and on conformational energy calculations, we predicted that peptide T adopts a structure much like that for residues 19-26 in RNase A. A critical feature is a bend involving residues Thr 4-Asn 7 in peptide T corresponding to Ser 22-Tyr 25 in the RNase A peptide. Our proposed structure for peptide T has recently been confirmed by Cotelle et al. (Biochem. Biophys. Res. Commun. 171, 596-602). We now show directly that the RNase A peptide, with Met replacing Cys 26 to prevent disulfide exchange reactions, strongly induces monocyte-chemotaxis that is blocked by anti-CD4 monoclonal antibody. Both peptide T and RNase A fail to induce chemotaxis, however, in neutrophils which do not express surface CD4 receptors. These results suggest that both peptides interact with the CD4 receptor in inducing monocyte chemotaxis. We have also prepared cyclo-RNase A peptide with Met 26. Using molecular dynamics and conformational energy calculations, we find that the cyclic peptide cannot form a bend structure involving Ser 22-Tyr 25 that is superimposable on the RNase A bend. Indeed, we find that this peptide is inactive in inducing monocyte chemotaxis despite the fact that its amino acid sequence is identical to that of the open chain form. This result suggests that a correlation between the beta-bend structure of the RNase A peptide and peptide T and their abilities to bind to the CD4 receptor. C1 SUNY HLTH SCI CTR,DEPT PATHOL & BIOCHEM,750 E ADAMS ST,SYRACUSE,NY 13210. HETEROCYCLE RES CORP,NEW CITY,NY 10956. NYU MED CTR,DEPT MED,NEW YORK,NY 10016. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20897. RI Licht, Daniel/I-3370-2013; Friedman, Fred/D-4208-2016 OI Licht, Daniel/0000-0002-4080-843X; NR 24 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD OCT PY 1992 VL 11 IS 5 BP 475 EP 481 DI 10.1007/BF01025024 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JV894 UT WOS:A1992JV89400005 PM 1449597 ER PT J AU KETY, SS INGRAHAM, LJ AF KETY, SS INGRAHAM, LJ TI GENETIC TRANSMISSION AND IMPROVED DIAGNOSIS OF SCHIZOPHRENIA FROM PEDIGREES OF ADOPTEES SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT INTERNATIONAL WORKSHOP ON GENETICS AND GENE EXPRESSION IN MENTAL ILLNESS CY OCT 28-31, 1991 CL VENICE, ITALY SP IST VENETO SCI LETT & ARTI ID SCHIZOTYPAL PERSONALITY-TRAITS; DSM-III; DISORDERS; VALIDITY; PARENTS AB In previous investigations of the prevalence of schizophrenic illness among the biological relatives of schizophrenic adoptees in Copenhagen and the remainder of Denmark, the operation of heritable spectrum illness was clearly implicated. The findings supporting that conclusion are briefly summarized. Classical chronic schizophrenia was found almost exclusively in the biological relatives of chronic schizophrenic probands and its prevalence was ten times greater than that in the biological relatives of controls. These were global diagnoses, made without knowledge of the relationships and family histories of the subjects, and based upon the descriptions of dementia praecox or schizophrenia by Kraepelin and Bleuler. They showed considerably greater sensitivity and at least equal specificity in comparison with diagnoses made on the same material in accordance with operational criteria as exemplified by DSM-III. The prevalence of a disorder in the biological relatives of adoptees with that disorder in comparison with biological relatives of control adoptees offers a useful test for the expression of genetic factors in the disorder, but also a much needed evaluation of the validity of diagnoses based on clinical observation. C1 NIMH,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NR 16 TC 9 Z9 9 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD OCT PY 1992 VL 26 IS 4 BP 247 EP 255 DI 10.1016/0022-3956(92)90031-I PG 9 WC Psychiatry SC Psychiatry GA KH019 UT WOS:A1992KH01900004 PM 1491351 ER PT J AU GINNS, EI EGELAND, JA ALLEN, CR PAULS, DL FALLS, K KEITH, TP PAUL, SM AF GINNS, EI EGELAND, JA ALLEN, CR PAULS, DL FALLS, K KEITH, TP PAUL, SM TI UPDATE ON THE SEARCH FOR DNA MARKERS LINKED TO MANIC-DEPRESSIVE ILLNESS IN THE OLD ORDER AMISH SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT INTERNATIONAL WORKSHOP ON GENETICS AND GENE EXPRESSION IN MENTAL ILLNESS CY OCT 28-31, 1991 CL VENICE, ITALY SP IST VENETO SCI LETT & ARTI ID BIPOLAR AFFECTIVE-DISORDERS; LINKAGE AB In this report we describe our efforts to identify a gene involved in bipolar illness using a large, multigenerational Old Order Amish pedigree with many affected individials. The original collection of cell lines from Amish pedigree 110 has been extended to include 169 individuals. We have used over 250 markers spaced at approximately 20 centiMorgans that detect restriction length fragment polymorphisms, but no LOD scores greater than 3 have been obtained from pairwise linkage analyses. We are expanding our collection of cell lines from both normal and affected family members and updating our diagnostic data as we continue our systematic screening of the genome for a gene involved in bipolar illness. C1 UNIV MIAMI,DEPT PSYCHIAT,MIAMI,FL 33101. YALE UNIV,SCH MED,CTR CHILD STUDY,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. COLLABORAT RES INC,DEPT HUMAN GENET & MOLEC BIOL,WALTHAM,MA. NIMH,CLIN NEUROSCI BRANCH,IRP,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RP GINNS, EI (reprint author), NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,IRP,BETHESDA,MD 20892, USA. NR 13 TC 12 Z9 12 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD OCT PY 1992 VL 26 IS 4 BP 305 EP 308 DI 10.1016/0022-3956(92)90037-O PG 4 WC Psychiatry SC Psychiatry GA KH019 UT WOS:A1992KH01900010 PM 1362775 ER PT J AU MIRSKY, AF LOCHHEAD, SJ JONES, BP KUGELMASS, S WALSH, D KENDLER, KS AF MIRSKY, AF LOCHHEAD, SJ JONES, BP KUGELMASS, S WALSH, D KENDLER, KS TI ON FAMILIAL FACTORS IN THE ATTENTIONAL DEFICIT IN SCHIZOPHRENIA - A REVIEW AND REPORT OF 2 NEW SUBJECT SAMPLES SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article; Proceedings Paper CT INTERNATIONAL WORKSHOP ON GENETICS AND GENE EXPRESSION IN MENTAL ILLNESS CY OCT 28-31, 1991 CL VENICE, ITALY SP IST VENETO SCI LETT & ARTI ID CONTINUOUS PERFORMANCE-TEST; EVENT-RELATED POTENTIALS; BRAIN-STEM RESPONSES; ISRAELI HIGH-RISK; SUSTAINED ATTENTION; CHILDREN AB We review the literature on attentional impairment in schizophrenics and their first-degree relatives and present new information from ongoing family studies of the disorder in Ireland and Israel. Subjects were administered a neuropsychological test battery (the NIMH Attention Battery) intended to measure four different elements of attention: encode, focus/execute, sustain, and shift. Results from both samples indicated that schizophrenic subjects performed most poorly on the tests, the control subjects performed best, and the scores of the relatives fell somewhere between the other two groups. Separation among subject groups was most significant for those tests comprising the focus/execute and sustain elements. Some of the results indicate, as well, that tests of auditory sustained attention may be the most discriminating of all. Overall comparison of the Irish and Israeli cohorts revealed striking differences. While within cohort differences remained, subjects from the Irish sample performed more poorly on many of the tests than Israeli subjects. This between-cohort difference was not found in the sustain element, as measured by the Continuous Performance Test. The socio-cultural implications of these findings are discussed with respect to future neuropsychological studies of schizophrenia. RP MIRSKY, AF (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BLDG 10,ROOM 4C-110,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 62 TC 77 Z9 77 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD OCT PY 1992 VL 26 IS 4 BP 383 EP 403 DI 10.1016/0022-3956(92)90042-M PG 21 WC Psychiatry SC Psychiatry GA KH019 UT WOS:A1992KH01900015 PM 1491359 ER PT J AU GANDJBAKHCHE, AH BONNER, RF NOSSAL, R AF GANDJBAKHCHE, AH BONNER, RF NOSSAL, R TI SCALING RELATIONSHIPS FOR ANISOTROPIC RANDOM-WALKS SO JOURNAL OF STATISTICAL PHYSICS LA English DT Article DE ANISOTROPIC RANDOM WALKS; MULTIPLE SCATTERING; SCALING RELATIONS ID WEAK LOCALIZATION; TISSUE; TIME; INVERSION; PHOTONS; LIGHT; MODEL; MEDIA AB Aspects of transport in a highly multiple-scattering environment are investigated by examining random walkers moving in media having anisotropic angular scattering cross sections (turn-angle distributions). A general expression is Obtained for the mean square displacement [x2] of a random walker executing an n-step walk in an infinite homogeneous material, and results are used to predict scaling relations for the probability gamma(rho) that a walker returns to the planar surface of a semi-infinite medium at a distance rho from the point of its insertion. RP GANDJBAKHCHE, AH (reprint author), NIH,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015 NR 31 TC 36 Z9 36 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4715 J9 J STAT PHYS JI J. Stat. Phys. PD OCT PY 1992 VL 69 IS 1-2 BP 35 EP 53 DI 10.1007/BF01053781 PG 19 WC Physics, Mathematical SC Physics GA JT172 UT WOS:A1992JT17200003 ER PT J AU KRSMANOVIC, LZ VIRMANI, MA STOJILKOVIC, SS CATT, KJ AF KRSMANOVIC, LZ VIRMANI, MA STOJILKOVIC, SS CATT, KJ TI ACTIONS OF ACETYL-L-CARNITINE ON THE HYPOTHALAMOPITUITARY GONADAL SYSTEM IN FEMALE RATS SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID GONADOTROPIN-RELEASING HORMONE; FOLLICLE-STIMULATING-HORMONE; DISPERSED PITUITARY-CELLS; 4-DAY ESTROUS-CYCLE; LUTEINIZING-HORMONE; SECRETION; INVITRO; RESPONSIVENESS; PROLACTIN; BRAIN AB Acetyl-L-carnitine (ALC) is known to affect several aspects of neuronal activity. To evaluate the neuroendocrine actions of this compound, several endocrinological parameters were followed in ALC-treated and control animals during recovery from dark-induced anestrus. In treated animals, serum luteinizing hormone (LH) and prolactin levels were higher than those of controls during the proestrous and estrous phases of the cycle, and serum estradiol levels were higher during estrus. No significant changes were observed in serum levels of follicle-stimulating hormone and progesterone. Uterine weight was increased in ALC-treated rats during proestrus and estrus, but not in diestrus. The basal release of gonadotropin-releasing hormone (GnRH) from perifused hypothalamic slices of ALC-treated animals was elevated at proestrus and diestrus, and GnRH release elicited by high K+ was higher during all three phases of the cycle. The basal release of LH from perifused pituitaries of treated animals was elevated in diestrus, and the LH response to GnRH was higher in estrus and diestrus I. Depolarization with K+ caused increased LH secretion during proestrus and estrus in treated animals. In contrast to these effects of ALC treatment in vivo, no direct effects of ALC were observed during short- or long-term treatment of cultured pituitary cells. These results indicate that ALC treatment influences hypothalamo-pituitary function in a cycle stage-dependent manner, and increases the secretory activity of gonadotrophs and lactotrophs. Since no effects of ALC on basal and agonist-induced secretory responses of gonadotrophs were observed in vitro, it is probable that its effects on gonadotropin release are related to enhancement of GnRH neuronal function in the hypothalamus. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. SIGMA TAU PHARMACEUT CO,DEPT PHARMACOL,RES & DEV,I-00040 POMEZIA,ITALY. NR 42 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD OCT PY 1992 VL 43 IS 4 BP 351 EP 358 DI 10.1016/0960-0760(92)90170-N PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA JR453 UT WOS:A1992JR45300012 PM 1390285 ER PT J AU GIFT, HC NEWMAN, JF AF GIFT, HC NEWMAN, JF TI ORAL HEALTH ACTIVITIES OF UNITED-STATES CHILDREN - RESULTS OF A NATIONAL-HEALTH INTERVIEW SURVEY SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB Data from the 1989 National Health Interview Survey show oral health activities for U.S. children aged 2-17. Key population subgroups neither received optimal preventive care nor visited a dentist regularly. C1 GEORGIA STATE UNIV,HLTH ADM STUDIES,ATLANTA,GA 30303. RP GIFT, HC (reprint author), NIDR,DIS PREVENT & HLTH PROMOT BRANCH,EPIDEMIOL & ORAL DIS PROGRAM,BETHESDA,MD 20892, USA. NR 10 TC 25 Z9 25 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1992 VL 123 IS 10 BP 96 EP & PG 0 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JR624 UT WOS:A1992JR62400018 PM 1401600 ER PT J AU BROWN, P GALVEZ, S GOLDFARB, LG NIETO, A CARTIER, L GIBBS, CJ GAJDUSEK, DC AF BROWN, P GALVEZ, S GOLDFARB, LG NIETO, A CARTIER, L GIBBS, CJ GAJDUSEK, DC TI FAMILIAL CREUTZFELDT-JAKOB DISEASE IN CHILE IS ASSOCIATED WITH THE CODON-200 MUTATION OF THE PRNP AMYLOID PRECURSOR GENE ON CHROMOSOME-20 SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE CREUTZFELDT-JAKOB DISEASE; PRNP GENE; SPONGIFORM ENCEPHALOPATHY ID LIBYAN JEWS; SLOVAKIA; PROTEIN AB We have found the codon 200Lys mutation in 6 Chilean CJD families, including a family in the rural case cluster in Chillan. Thus, all 3 of the known clusters of CJD, in Slovakia, Libyan-born Israeli Jews, and Chile, are linked to the presence of the same mutation. The phenotypic features of the disease in these families are similar to those reported for other clustered or individual families elsewhere in the world. The heterogeneous genetic composition of the Chilean population interpreted in light of historical migration patterns suggests that the mutation may have entered Chile by Jewish emigration from Spain. C1 HOSP SALVADOR, SERV NEUROL, DEPT NEUROPATOL, SANTIAGO, CHILE. INST NEUROCIRUGIA INVEST CEREBR ALFONSO ASENJO, SANTIAGO, CHILE. RP BROWN, P (reprint author), NIH, INST NEUROL & COMMUNICAT DISORDERS, CNS STUDIES LAB, BLDG 36, BETHESDA, MD 20892 USA. NR 15 TC 49 Z9 50 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT PY 1992 VL 112 IS 1-2 BP 65 EP 67 DI 10.1016/0022-510X(92)90133-6 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA JV895 UT WOS:A1992JV89500010 PM 1469441 ER PT J AU SCHMITT, JM KNUTTEL, A KNUTSON, JR AF SCHMITT, JM KNUTTEL, A KNUTSON, JR TI INTERFERENCE OF DIFFUSIVE LIGHT WAVES SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID TIME; APPROXIMATION; TRANSPORT; TISSUE; MEDIA AB We examine interference effects resulting from the superposition of photon-density waves produced by coherently modulated light incident upon a turbid medium. Photon-diffusion theory is used to derive expressions for the ac magnitude and phase of the aggregate diffusive wave produced in full- and half-space volumes by two sources. Using a frequency-domain spectrometer operating at 410 MHz, we verify interference patterns predicted by the model in scattering samples having optical properties similar to those of skin tissue. Potential imaging applications of interfering diffusive waves are discussed in the context of the theoretical and experimental results. C1 NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. NHLBI,CELLULAR BIOL LAB,BETHESDA,MD 20892. RP SCHMITT, JM (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 23 TC 69 Z9 69 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0740-3232 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD OCT PY 1992 VL 9 IS 10 BP 1832 EP 1843 DI 10.1364/JOSAA.9.001832 PG 12 WC Optics SC Optics GA JQ422 UT WOS:A1992JQ42200019 PM 1403242 ER PT J AU DELVECCHIO, AM ROMANCZUK, H HOWLEY, PM BAKER, CC AF DELVECCHIO, AM ROMANCZUK, H HOWLEY, PM BAKER, CC TI TRANSIENT REPLICATION OF HUMAN PAPILLOMAVIRUS DNAS SO JOURNAL OF VIROLOGY LA English DT Article ID EARLY REGION TRANSFORMATION; CERVICAL-CARCINOMA CELLS; HPV18 REGULATORY REGION; LONG CONTROL REGION; BOVINE PAPILLOMAVIRUS; BINDING PHOSPHOPROTEIN; MOLECULAR-CLONING; NONCODING REGION; PHYSICAL STATE; TYPE-16 AB Information on papillomavirus DNA replication has primarily derived from studies with bovine papillomavirus type 1 (BPV-1). Our knowledge of DNA replication of the human papillomaviruses (HPVs) is quite limited, in part because of the lack of a cell culture system capable of supporting the stable replication of HPV DNA. This study demonstrates that the full-length genomic DNAs of HPV types 11 and 18 (HPV-11 and HPV-18), but not HPV-16, are able to replicate transiently after transfection into several different human squamous cell carcinoma cell lines. This system was used to identify the viral cis and trans elements required for DNA replication. The viral origins of replication were localized to a region of the viral long control region. Like BPV-1, El and E2 were the only viral factors required in trans for the replication of plasmids containing the origin. Cotransfection of a plasmid expressing the El open reading frame (ORF) from HPV-11 with a plasmid that expresses the E2 ORF from HPV-6, HPV-11, HPV-16, or HPV-18 supported the replication of plasmid DNAs containing the origin regions of HPV-11, HPV-16, or HPV-18, indicating that there are functions shared among the corresponding E1 and E2 proteins and origins of these viruses. Although HPV-16 genomic DNA did not replicate by itself under experimental conditions that supported the replication of HPV-11 and HPV-18 genomic DNAs, expression of the HPV-16 early region functions from a strong heterologous promoter supported the replication of a cotransfected plasmid containing the HPV-16 origin of replication. This finding suggests that the inability of the HPV-16 genomic DNA to replicate transiently in the cell lines tested was most likely due to insufficient expression of the viral E1 and/or E2 genes required for DNA replication. C1 NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. NR 56 TC 148 Z9 153 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1992 VL 66 IS 10 BP 5949 EP 5958 PG 10 WC Virology SC Virology GA JN267 UT WOS:A1992JN26700028 PM 1326651 ER PT J AU OLMSTED, RA LANGLEY, R ROELKE, ME GOEKEN, RM ADGERJOHNSON, D GOFF, JP ALBERT, JP PACKER, C LAURENSON, MK CARO, TM SCHEEPERS, L WILDT, DE BUSH, M MARTENSON, JS OBRIEN, SJ AF OLMSTED, RA LANGLEY, R ROELKE, ME GOEKEN, RM ADGERJOHNSON, D GOFF, JP ALBERT, JP PACKER, C LAURENSON, MK CARO, TM SCHEEPERS, L WILDT, DE BUSH, M MARTENSON, JS OBRIEN, SJ TI WORLDWIDE PREVALENCE OF LENTIVIRUS INFECTION IN WILD FELINE SPECIES - EPIDEMIOLOGIC AND PHYLOGENETIC ASPECTS SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUSES; AFRICAN-GREEN MONKEYS; SEROEPIDEMIOLOGIC SURVEY; NUCLEOTIDE-SEQUENCE; GENOME ORGANIZATION; GENETIC DIVERSITY; CERCOCEBUS-ATYS; ORIGINS; RETROVIRUSES; ANTIBODIES AB The natural occurrence of lentiviruses closely related to feline immunodeficiency virus (FIV in nondomestic felid species is shown here to be worldwide. Cross-reactive antibodies to FIV were common in several free-ranging populations of large cats, including East African lions and cheetahs of the Serengeti ecosystem and in puma (also called cougar or mountain lion) populations throughout North America. Infectious puma lentivirus (PLV) was isolated from several Florida panthers, a severely endangered relict puma subspecies inhabiting the Big Cypress Swamp and Everglades ecosystems in southern Florida. Phylogenetic analysis of PLV genomic sequences from disparate geographic isolates revealed appreciable divergence from domestic cat FIV sequences as well as between PLV sequences found in different North American locales. The level of sequence divergence between PLV and FIV was greater than the level of divergence between human and certain simian immunodeficiency viruses, suggesting that the transmission of FIV between feline species is infrequent and parallels in time the emergence of HIV from simian ancestors. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,WASHINGTON,DC 20057. NIAID,INFECT DIS LAB,ROCKVILLE,MD 20852. FLORIDA GAME & FRESHWATER FISH COMMISS,WILDLIFE RES LAB,GAINESVILLE,FL 32601. UNIV MINNESOTA,DEPT ECOL & BEHAV BIOL,MINNEAPOLIS,MN 55455. UNIV CAMBRIDGE,DEPT ZOOL,CAMBRIDGE CB2 3EJ,ENGLAND. UNIV CALIF DAVIS,DEPT WILDLIFE & FISHERIES BIOL,DAVIS,CA 95616. ETOSHA ECOL INST,OUTJO,NAMIBIA. SMITHSONIAN INST,NATL ZOOL PK,DEPT ANIM HLTH,WASHINGTON,DC 20008. FU NIAID NIH HHS [N01-AI-72623] NR 47 TC 139 Z9 139 U1 2 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1992 VL 66 IS 10 BP 6008 EP 6018 PG 11 WC Virology SC Virology GA JN267 UT WOS:A1992JN26700034 PM 1382145 ER PT J AU MUKHOPADHYAYA, R WOLFF, L AF MUKHOPADHYAYA, R WOLFF, L TI NEW SITES OF PROVIRAL INTEGRATION ASSOCIATED WITH MURINE PROMONOCYTIC LEUKEMIAS AND EVIDENCE FOR ALTERNATE MODES OF C-MYB ACTIVATION SO JOURNAL OF VIROLOGY LA English DT Article ID B-CELL LYMPHOMAS; NUCLEOTIDE-SEQUENCE; INITIATION CODON; MYELOID TUMORS; MESSENGER-RNA; BALB/C MICE; VIRUS; INDUCTION; PROTEIN; LINE AB Murine promonocytic leukemias involving insertional mutagenesis of the c-myb locus can be induced by replication-competent retroviruses. In previously studied promonocytic leukemic cells induced by Moloney murine leukemia virus (called MML), the provirus has been invariably integrated upstream of exons 3 or 4 and the leukemic cells expressed aberrant RNAs with fused virus-myb sequences. Furthermore, Myb expressed by these cells has been shown to be truncated by 47 or 71 amino acids. The present report examines the mechanisms of myb activation in leukemias induced by two other retroviruses, amphotropic virus 4070A and Friend strain FB29 (the leukemias are called AMPH-ML and FB-ML, respectively). This study revealed two additional c-myb proviral,insertion sites in these promonocytic leukemias. One FB-ML had a proviral integration in exon 9, and expressed a C-terminally truncated Myb protein of 47 kDa similar to that previously demonstrated to be expressed in the myelomonocytic cell lines NFS60 and VFL-2. However, a sequence of reverse-transcribed and amplified RNA from this leukemia demonstrated that the truncation involved a loss of 248 amino acids compared with a loss of 240 amino acids in the myelomonocytic cell lines. Another leukemia had a provirus integrated in the 5' end of c-myb upstream of exon 2 (in the first intron) and produced a Myb protein that was indistinguishable on sodium dodecyl sulfate-polyacrylamide gel electrophoresis from normal Myb. This latter leukemia (FB-ML R1-4-10) expressed Myb with the smallest N-terminal truncation observed so far in promonocytic leukemias; translation begins at an ATG within c-myb exon 2, leading to loss of only 20 amino acids from the N terminus. Unlike the proteins produced in Moloney murine leukemia virus-induced promonocytic leukemias (MML) that have larger truncations, this protein has an intact DNA binding region and does not contain N-terminal amino acids encoded by gag. However, this protein is similar to all N-terminally truncated Mybs so far studied, in that the truncation resulted in deletion of a casein kinase II phosphorylation site which has been proposed to be involved in regulation of DNA binding. C1 NCI,GENET LAB,BETHESDA,MD 20892. NR 37 TC 46 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1992 VL 66 IS 10 BP 6035 EP 6044 PG 10 WC Virology SC Virology GA JN267 UT WOS:A1992JN26700037 PM 1527851 ER PT J AU OTT, DE KELLER, J SILL, K REIN, A AF OTT, DE KELLER, J SILL, K REIN, A TI PHENOTYPES OF MURINE LEUKEMIA VIRUS-INDUCED TUMORS - INFLUENCE OF 3' VIRAL CODING SEQUENCES SO JOURNAL OF VIROLOGY LA English DT Article ID FOCUS-FORMING VIRUSES; T-CELL DEVELOPMENT; DISEASE SPECIFICITY; CHAIN GENES; MOLONEY; LYMPHOMAS; RECEPTOR; FRIEND; REARRANGEMENT; RECOMBINANT AB Murine leukemia viruses (MuLVs) induce leukemias and lymphomas in mice. We have used fluorescence-activated cell sorter analysis to determine the hematopoietic phenotypes of tumor cells induced by a number of MuLVs. Tumor cells induced by ecotropic Moloney, amphotropic 4070A and 10A1 MuLVs and by two chimeric MuLVs, Mo(4070A) and Mo(10A1), were examined with antibodies to 13 lineage-specific cell surface markers found on myeloid cell, T-cell, and B-cell lineages. The chimeric Mo(4070A) and Mo(10A1) MuLVs, consisting of Moloney MULV with the carboxy half of the Pol region and nearly all of the Env region of 4070A and 10A1, respectively, were constructed to examine the possible influence of these sequences on Moloney MuLV-induced tumor cell phenotypes. ID some instances, these phenotypic analyses were supplemented by Southern blot analysis for lymphoid cell-specific genomic DNA rearrangements at the immunoglobulin heavy-chain, the T-cell receptor-gamma, and the T-cell receptor beta-loci. The results of our analysis showed that Moloney MULV, 4070A, Mo(4070A), and Mo(10A1) induced mostly T-cell tumors. Moloney MULV and Mo(4070A) induced a wide variety of T-cell phenotypes, ranging from immature to mature phenotypes, while 4070A induced mostly prothymocyte and double-negative (CD4- CD8-) T-cell tumors. The tumor phenotypes obtained with 10A1 and Mo(10A1) were each less variable than those obtained with the other MuLVs tested. 10A1 uniformly induced a tumor consisting of lineage marker-negative cells that lack lymphoid cell-specific DNA rearrangements and histologically appear to be early undifferentiated erythroid cell-like precursors. The Mo(10A1) chimera consistently induced an intermediate T-cell tumor. The chimeric constructions demonstrated that while 4070A 3' pol and env sequences apparently did not influence the observed tumor cell phenotypes, the 10A1 half of pol and env had a strong effect on the phenotypes induced by Mo(10A1) that resulted in a phenotypic consistency not seen with other viruses. This result implicates 10A1 env in an active role in the tumorigenic process. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. PRI DYNCORP INC,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP OTT, DE (reprint author), PRI DYNCORP INC,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102, N01-CO-74101] NR 56 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1992 VL 66 IS 10 BP 6107 EP 6116 PG 10 WC Virology SC Virology GA JN267 UT WOS:A1992JN26700044 PM 1326661 ER PT J AU BERGER, EA SISLER, JR EARL, PL AF BERGER, EA SISLER, JR EARL, PL TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN MOLECULES CONTAINING MEMBRANE FUSION-IMPAIRING MUTATIONS IN THE V3-REGION EFFICIENTLY UNDERGO SOLUBLE CD4-STIMULATED GP120 RELEASE SO JOURNAL OF VIROLOGY LA English DT Note ID PRINCIPAL NEUTRALIZING DOMAIN; HUMAN LYMPHOCYTES-T4+; CELL TROPISM; CD4 BINDING; HIV-1; GENE; IDENTIFICATION; DISSOCIATION; DETERMINANT; SURFACE AB The ability of soluble forms of CD4 to induce gp120 release from the human immunodeficiency virus type 1 envelope glycoprotein complex may reflect molecular events associated with membrane fusion. The third hypervariable (V3) region of gp120 appears to play a role in fusion independent of CD4 binding. We demonstrate herein that envelope glycoprotein molecules rendered fusion defective by mutations in conserved residues within the V3 region nevertheless undergo efficient soluble CD4-induced gp120 release. RP BERGER, EA (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 42 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1992 VL 66 IS 10 BP 6208 EP 6212 PG 5 WC Virology SC Virology GA JN267 UT WOS:A1992JN26700059 PM 1527858 ER PT J AU HUBBERT, NL SEDMAN, SA SCHILLER, JT AF HUBBERT, NL SEDMAN, SA SCHILLER, JT TI HUMAN PAPILLOMAVIRUS TYPE-16-E6 INCREASES THE DEGRADATION RATE OF P53 IN HUMAN KERATINOCYTES SO JOURNAL OF VIROLOGY LA English DT Note ID CARCINOMA CELL-LINES; EPITHELIAL-CELLS; E6 ONCOPROTEIN; EARLY GENES; PROTEIN; TRANSFORMATION; INVITRO; E7; IDENTIFICATION; TRANSCRIPTION AB The E6 proteins of the high-risk human papillomaviruses (HPVs) have been shown to form a complex with and induce the degradation of human p53 in vitro. To determine whether p53 is degraded more rapidly in cells expressing E6 in vivo, the half-life of p53 was determined by pulse-chase analysis in early-passage normal human keratinocytes and fibroblasts, human keratinocytes immortalized with HFV type 16 (HPV16) E6 plus E7, and nonimmortal keratinocytes transfected with E6. The results of these experiments indicate that (i) the half-life of newly synthesized p53 is relatively long (4 h) in early-passage human keratinocytes and fibroblasts but short in keratinocytes expressing E6 (15 to 30 min), (ii) a similar increased rate of p53 degradation was measured in lines immortalized with HPV16 E6 plus E7 and senescent cells expressing E6, indicating that this increase is not simply the result of selection in the immortalized lines, and (iii) very low levels of expression of E6 result in a greatly decreased half-life of p53, suggesting that E6 acts in a catalytic manner. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [TA-CA-B032] NR 29 TC 160 Z9 166 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1992 VL 66 IS 10 BP 6237 EP 6241 PG 5 WC Virology SC Virology GA JN267 UT WOS:A1992JN26700065 PM 1326671 ER PT J AU KITTUR, DS PETRONIS, J FRENCH, AW ADLER, W AF KITTUR, DS PETRONIS, J FRENCH, AW ADLER, W TI TRANSPLANTATION OF HALF KIDNEYS IN SWINE .1. LONG-TERM SURVIVORS OF HEMIRENAL AUTOTRANSPLANTS SO LABORATORY ANIMAL SCIENCE LA English DT Article ID DIETARY-PROTEIN INTAKE; RENAL ABLATION; DOGS; REDUCTION; MASS AB We describe a novel model of hemirenal transplantation in swine wherein one-half of one kidney is autotransplanted by modifications of standard vascular anastomoses and ureteropyelostomy. Two pigs with hemirenal transplants performed in this manner have not only survived but have grown normally and had decreased but stable renal function for more than 1 year. The model confirms that one-fourth of the total renal mass is sufficient to sustain life and growth in pigs. It is anticipated that this model could be used to study the effects of renal ablation on remnant nephrons in pigs. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP KITTUR, DS (reprint author), JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205, USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD OCT PY 1992 VL 42 IS 5 BP 467 EP 472 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA JV915 UT WOS:A1992JV91500008 PM 1460845 ER PT J AU FORSYTHE, DB PAYTON, AJ DIXON, D MYERS, PH CLARK, JA SNIPE, JR AF FORSYTHE, DB PAYTON, AJ DIXON, D MYERS, PH CLARK, JA SNIPE, JR TI EVALUATION OF TELAZOL-XYLAZINE AS AN ANESTHETIC COMBINATION FOR USE IN SYRIAN-HAMSTERS SO LABORATORY ANIMAL SCIENCE LA English DT Article ID TILETAMINE; ZOLAZEPAM; KETAMINE AB The availability of safe parenteral anesthetics for use in Syrian hamsters is limited. We evaluated the effects of Telazol-xylazine (TZX) combinations with respect to anesthetic efficacy and potential for tissue damage. Two dose levels of the combination were administered by both the intraperitoneal (IP) and intramuscular (IM) routes. TZX by the IM route failed to consistently produce anesthesia and caused gross and histopathologic muscle lesions. IP administration of 20 mg/kg Telazol combined with 10 mg/kg xylazine was adequate for restraint purposes. IP administration of 30 mg/kg Telazol combined with 10 mg/kg xylazine produced a safe, reliable level of surgical anesthesia without evidence of gross or histopathologic lesions. There was no nephrotoxicity at either concentration of the anesthetic. A dose level of TZX that provides safe parenteral anesthesia in Syrian hamsters was determined. C1 UNIV N CAROLINA,DIV LAB ANIM MED,CHAPEL HILL,NC 27599. NIEHS,EXPTL TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. RP FORSYTHE, DB (reprint author), NIEHS,COMPARAT MED BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 4 Z9 5 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD OCT PY 1992 VL 42 IS 5 BP 497 EP 502 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA JV915 UT WOS:A1992JV91500014 PM 1460851 ER PT J AU MARSDEN, ER HU, ZY FUJIO, K NAKATSUKASA, H THORGEIRSSON, SS EVARTS, RP AF MARSDEN, ER HU, ZY FUJIO, K NAKATSUKASA, H THORGEIRSSON, SS EVARTS, RP TI EXPRESSION OF ACIDIC FIBROBLAST GROWTH-FACTOR IN REGENERATING LIVER AND DURING HEPATIC DIFFERENTIATION SO LABORATORY INVESTIGATION LA English DT Article DE OVAL CELLS; ITO CELLS; INSITU HYBRIDIZATION ID NORMAL RAT-LIVER; ANGIOGENIC PROTEIN; FACTOR FAMILY; FACTOR-ALPHA; BINDING; CELLS; PROLIFERATION; HEMATOPOIESIS; AUTOCRINE; REGULATOR AB BACKGROUND: Acidic fibroblast growth factor belongs to a family of growth factors that show a high affinity for heparin sulfate proteoglycans. In vitro, it participates in various cellular functions including proliferation, differentiation, angiogenesis, and cell migration, but in vivo, the physiologic role of this growth factor is still not clearly defined. EXPERIMENTAL DESIGN: The level of expression and also cellular distribution of transcripts for acidic fibroblast growth factor (aFGF) were studied in adult rat liver after partial hepatectomy and during hepatic differentiation in fetal, neonatal, and adult livers by Northern analysis and in situ hybridization techniques. RESULTS: After partial hepatectomy a significant increase in the transcripts for aFGF was observed at 24 hours, whereas at 4 and 12 hours after the operation, the level of transcripts were similar to those of sham-operated animals. In the postnatal liver a high level of aFGF expression was present when the most evident transition from 2 to 3 cell thick hepatic cords to normal hepatic structure is taking place (Ogawa K, Medine A, Farber E. Br J Cancer 1979;40:782-90). In contrast during the prenatal period, when the liver is still a hemopoietic organ and only a small number of sinusoids are present, low level of aFGF transcripts could be found. Animals treated with 2-acetylaminofluorene and partial hepatectomy (Evarts RP, Nagy P, Marsden E, Thorgeirsson SS. Carcinogenesis 1987;8:1737-40) displayed a marked increase in hepatic aFGF transcripts at the peak of proliferation of primitive liver epithelial cells (oval cells) and perisinusoidal stellate cells (Ito cells) in addition to hepatocytes. In situ hybridization combined with immunocytochemistry using oval and Ito cell specific antibodies revealed the presence of transcripts both in oval cells and Ito cells. Basophilic areas composed of small hepatocytes had a 3-fold increase in the level of transcripts as compared with the surrounding hepatocytes. CONCLUSIONS: These experiments demonstrate that the expression of aFGF is highest during the late stages of hepatic morphogenesis in newborn animals as well as during hepatic differentiation in adult liver. C1 NCI, EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 35 TC 77 Z9 79 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 1992 VL 67 IS 4 BP 427 EP 433 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA JU688 UT WOS:A1992JU68800003 PM 1279268 ER PT J AU PASSANITI, A TAYLOR, RM PILI, R GUO, Y LONG, PV HANEY, JA PAULY, RR GRANT, DS MARTIN, GR AF PASSANITI, A TAYLOR, RM PILI, R GUO, Y LONG, PV HANEY, JA PAULY, RR GRANT, DS MARTIN, GR TI METHODS IN LABORATORY INVESTIGATION - A SIMPLE, QUANTITATIVE METHOD FOR ASSESSING ANGIOGENESIS AND ANTIANGIOGENIC AGENTS USING RECONSTITUTED BASEMENT-MEMBRANE, HEPARIN, AND FIBROBLAST GROWTH-FACTOR SO LABORATORY INVESTIGATION LA English DT Article DE NEOVASCULARIZATION; MATRIGEL ID ENDOTHELIAL-CELL GROWTH; VASCULAR-PERMEABILITY FACTOR; TUMOR-INDUCED ANGIOGENESIS; CAPILLARY-LIKE STRUCTURES; NECROSIS-FACTOR-ALPHA; EXTRACELLULAR-MATRIX; INVITRO; INVIVO; INHIBITOR; LAMININ AB BACKGROUND: Blood vessel growth is necessary for normal tissue homeostasis and contributes to solid tumor growth. Methods to quantitate neovascularization should be useful in testing biological factors and drugs that regulate angiogenesis or to induce a vascular supply to promote wound healing. EXPERIMENTAL DESIGN: An extract of basement membrane proteins (Matrigel) was found to reconstitute into a gel when injected subcutaneously into C57/BL mice and to support an intense vascular response when supplemented with angiogenic factors. RESULTS: New vessels and von Willebrand factor antigen staining were apparent in the gel 2-3 days after injection, reaching a maximum after 3-5 days. Hemoglobin content of the gels was found to parallel the increase in vessels in the gel allowing ready quantitation. Angiogenesis was obtained with both acidic and basic fibroblast growth factors and was enhanced by heparin. Several substances were tested for angiostatic activity in this assay by coinjection in Matrigel with fibroblast growth factor and heparin. Platelet-derived growth factor BB, interleukin 1-beta, interleukin-6, and transforming growth factor-beta were potent inhibitors of neovascularization induced by fibroblast growth factor. Tumor necrosis factor-alpha did not alter the response but was alone a potent inducer of neovascularization when coinjected with Matrigel and heparin. Consistent with the previously demonstrated importance of collagenase in mediating endothelial cell invasion, a tissue inhibitor of metalloproteinases that also inhibits collagenases was found to be a potent inhibitor of fibroblast growth factor-induced angiogenesis. CONCLUSIONS: Our assay allows the ready quantitative assessment of angiogenic and antiangiogenic factors and should be useful in the isolation of endothelial cells from the capillaries that penetrate into the gel. C1 JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT DERMATOL,BALTIMORE,MD 21205. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP PASSANITI, A (reprint author), NIA,GERONTOL RES CTR,BIOL CHEM & CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 69 TC 684 Z9 700 U1 0 U2 22 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 1992 VL 67 IS 4 BP 519 EP 528 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA JU688 UT WOS:A1992JU68800014 PM 1279270 ER PT J AU RAFFELD, M SANDER, CA YANO, T JAFFE, ES AF RAFFELD, M SANDER, CA YANO, T JAFFE, ES TI MANTLE CELL LYMPHOMA - AN UPDATE SO LEUKEMIA & LYMPHOMA LA English DT Article DE LYMPHOMA; MANTLE ZONE; MANTLE ZONE LYMPHOMA AB Mantle cell lymphoma is a distinctive pathologic entity that incorporates the previous histopathologic categories of centrocytic lymphoma and lymphocytic lymphoma of intermediate differentiation. These lymphomas are characterized by common histologic and immunologic characteristics that suggest derivation from the follicular mantle zone. Mantle cell lymphomas are characterized by the t(11;14) (q13;q32) translocation and its molecular counterpart bcl-1 rearrangement. This translocation activates a gene called BCL-1/PRAD-1. The identification of the BCL-1 gene product as a cyclin has added a new dimension to our understanding of the variety of mechanisms involved in lymphomagenesis. RP RAFFELD, M (reprint author), NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N110,BETHESDA,MD 20892, USA. NR 0 TC 30 Z9 30 U1 1 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 1992 VL 8 IS 3 BP 161 EP 166 DI 10.3109/10428199209054902 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA JZ433 UT WOS:A1992JZ43300001 PM 1490145 ER PT J AU KARP, JE BRODER, S AF KARP, JE BRODER, S TI THE PATHOGENESIS OF AIDS LYMPHOMAS - A FOUNDATION FOR ADDRESSING THE CHALLENGES OF THERAPY AND PREVENTION SO LEUKEMIA & LYMPHOMA LA English DT Article DE IMMUNODEFICIENCY; LYMPHOMA; C-MYC; EPSTEIN-BARR VIRUS; INTERLEUKINS AB The association between AIDS and a spectrum of malignancies relates to chronic, profound defects in both cellular and humoral mechanisms of immune surveillance. Ironically, as AIDS patients live longer in response to increasingly effective antiretroviral therapies, the incidence of AIDS-related malignancies will continue to rise. The emergence of non-Hodgkin's lymphomas (NHL) as a major sequela of HIV infection bears a striking relationship to depletion of CD4 lymphocytes, particularly below 50/mm3. The ability to interfere early in the course of active HIV infection with additional mechanisms that may promulgate transformed cell hyperproliferation and clonal expansion-growth factors, HIV itself or other viruses (Epstein-Barr, in particular), aberrant oncogene or tumor suppressor genes expression, factors that induce genetic instability or DNA damage or alter host or viral genome repair-might decrease the occurrence or prolong the time to development of AIDS-related malignancies. The development of antiretroviral strategies that confer long-term suppression of HIV activity and relative preservation of immune function are essential to the ultimate prevention of malignancies that arise as a consequence of HIV-induced immunosuppression. C1 NCI,9000 ROCKVILLE PIKE,BLDG 31,ROOM 11A48,BETHESDA,MD 20892. NR 0 TC 14 Z9 14 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 1992 VL 8 IS 3 BP 167 EP 188 DI 10.3109/10428199209054903 PG 22 WC Oncology; Hematology SC Oncology; Hematology GA JZ433 UT WOS:A1992JZ43300002 PM 1362682 ER PT J AU BROWN, LM GIBSON, R BURMEISTER, LF SCHUMAN, LM EVERETT, GD BLAIR, A AF BROWN, LM GIBSON, R BURMEISTER, LF SCHUMAN, LM EVERETT, GD BLAIR, A TI ALCOHOL-CONSUMPTION AND RISK OF LEUKEMIA, NON-HODGKINS-LYMPHOMA, AND MULTIPLE-MYELOMA SO LEUKEMIA RESEARCH LA English DT Article DE LEUKEMIA; LYMPHOMA; MYELOMA; ALCOHOL ID CANCER INCIDENCE; BREWERY WORKERS; BREAST-CANCER; MORTALITY; SMOKING; IOWA AB Population-based case-control interview studies of white men, 578 with leukemia, 622 with non-Hodgkin's lymphoma, and 820 controls from Iowa and Minnesota and 173 with multiple myeloma and 452 controls from Iowa, offered the opportunity to investigate the relationship of these cancers with alcohol consumption. Although drinkers had non-significantly elevated risks for specific subtypes of leukemia (acute lymphocytic leukemia (OR = 3.0), myelodysplasia (OR = 1.6), and other leukemia (OR = 1.5)) and multiple myeloma (OR = 1.3), there were no statistically significant findings and no dose-response gradients with amount of alcohol consumed. Thus, these data suggest that alcohol is not an important contributor to the etiology of lymphatic and hematopoietic tumors. C1 UNIV MINNESOTA,DEPT EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV IOWA,DEPT PREVENT MED,IOWA CITY,IA 52242. ORLANDO REG MED CTR INC,DEPT INTERNAL MED,ORLANDO,FL. RP BROWN, LM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [ES 03099] NR 32 TC 54 Z9 54 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD OCT PY 1992 VL 16 IS 10 BP 979 EP 984 DI 10.1016/0145-2126(92)90077-K PG 6 WC Oncology; Hematology SC Oncology; Hematology GA JT916 UT WOS:A1992JT91600005 PM 1405712 ER PT J AU LANGSLEY, G KASLOW, DC BARBOT, P BLISNICK, T PONNUDURAI, T BARALE, JC BRAUNBRETON, C AF LANGSLEY, G KASLOW, DC BARBOT, P BLISNICK, T PONNUDURAI, T BARALE, JC BRAUNBRETON, C TI A PLASMODIUM-FALCIPARUM GENE CODING FOR A 15-KILODALTON ANTIGEN EXPRESSED IN ASEXUAL STAGE PARASITES, GAMETOCYTES AND GAMETES SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Note DE INTRON; ANTIGEN; MALARIA; PLASMODIUM-FALCIPARUM; GAMETOCYTE; GAMETE ID ALDOLASE; TRANSLATION C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. CATHOLIC UNIV NIJMEGEN,DEPT MED PARASITOL,NIJMEGEN,NETHERLANDS. RP LANGSLEY, G (reprint author), PASTEUR INST,DEPT IMMUNOL,EXPTL PARASITOL UNIT,28 RUE DR ROUX,F-75015 PARIS,FRANCE. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD OCT PY 1992 VL 55 IS 1-2 BP 221 EP 224 DI 10.1016/0166-6851(92)90143-8 PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA JV683 UT WOS:A1992JV68300023 PM 1435872 ER PT J AU KALINEC, G NAZARALI, AJ HERMOUET, S XU, NZ GUTKIND, JS AF KALINEC, G NAZARALI, AJ HERMOUET, S XU, NZ GUTKIND, JS TI MUTATED ALPHA SUBUNIT OF THE GQ PROTEIN INDUCES MALIGNANT TRANSFORMATION IN NIH 3T3 CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHOLIPASE-C; DNA-SYNTHESIS; RECEPTOR; MITOGENESIS; ACTIVATION; MUTANT; GENES; VIRUS; CHAIN; PDGF AB The discovery of mutated, GTPase-deficient alpha subunits of G(s) or G(i2) in certain human endocrine tumors has suggested that heterotrimeric G proteins play a role in the oncogenic process. Expression of these altered forms of Galpha(s) or Galpha(i2) proteins in rodent fibroblasts activates or inhibits endogenous adenylyl cyclase, respectively, and causes certain alterations in cell growth. However, it is not clear whether growth abnormalities result from altered cyclic AMP synthesis. In the present study, we asked whether a recently discovered family of G proteins, G(q), which does not affect adenylyl cyclase activity, but instead mediates the activation of phosphatidylinositol-specific phospholipase C harbors transforming potential. We mutated the cDNA for the alpha subunit of murine G(q) in codons corresponding to a region involved in binding and hydrolysis of GTP. Similar mutations unmask the transforming potential of p21ras or activate the alpha subunits of G(s) or G(i2). Our results show that when expressed in NIH 3T3 cells, activating mutations convert Galpha(q) into a dominant acting oncogene. C1 NIDR,CELLULAR DEV & ONCOL LAB,MOLEC SIGNALLING GRP,BETHESDA,MD 20892. NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NIADDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 42 TC 136 Z9 136 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 OCT PY 1992 VL 12 IS 10 BP 4687 EP 4693 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JP798 UT WOS:A1992JP79800048 PM 1328859 ER PT J AU TACHIBANA, M HARA, Y VYAS, D HODGKINSON, C FEX, J GRUNDFAST, K ARNHEITER, H AF TACHIBANA, M HARA, Y VYAS, D HODGKINSON, C FEX, J GRUNDFAST, K ARNHEITER, H TI COCHLEAR DISORDER ASSOCIATED WITH MELANOCYTE ANOMALY IN MICE WITH A TRANSGENIC INSERTIONAL MUTATION SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID WAARDENBURG SYNDROME; STRIA VASCULARIS; INNER-EAR; MOUSE; LOCUS; DEFECT C1 NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. RP TACHIBANA, M (reprint author), NIDOCD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 31 TC 69 Z9 70 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD OCT PY 1992 VL 3 IS 5 BP 433 EP 445 PG 13 WC Neurosciences SC Neurosciences & Neurology GA JP073 UT WOS:A1992JP07300007 PM 19912887 ER PT J AU AUSTIN, MC SCHULTZBERG, M ABBOTT, LC MONTPIED, P EVERS, JR PAUL, SM CRAWLEY, JN AF AUSTIN, MC SCHULTZBERG, M ABBOTT, LC MONTPIED, P EVERS, JR PAUL, SM CRAWLEY, JN TI EXPRESSION OF TYROSINE-HYDROXYLASE IN CEREBELLAR PURKINJE NEURONS OF THE MUTANT TOTTERING AND LEANER MOUSE SO MOLECULAR BRAIN RESEARCH LA English DT Article DE INSITU HYBRIDIZATION; MESSENGER RNA; IMMUNOHISTOCHEMISTRY; NOREPINEPHRINE; GALANIN; GENETIC STRAIN; EPILEPSY ID NUCLEOTIDE-SEQUENCE ANALYSIS; NUCLEUS LOCUS COERULEUS; MEDULLARY CDNA LIBRARY; EFFERENT PROJECTIONS; INHERITED EPILEPSY; GALANIN PRECURSOR; CEREBRAL-CORTEX; RAT CEREBELLUM; MESSENGER-RNA; HYPOTHALAMUS AB In situ hybridization histochemistry, Northern blot analysis and immunohistochemistry were used to examine tyrosine hydroxylase (TH) mRNA concentrations and immunoreactivity in the locus coeruleus and cerebellum of the tottering (tg/tg), leaner (tg(la)/tg(la)), compound heterozygous (tg/tg(la)) and wild type control (+/+) mice, bred on a C57BL/6J background. Cerebellar Purkinje neurons, long considered to be GABAergic, showed high levels of TH mRNA in the caudal vermis and the lateral hemispheres of the cerebellum of tg/tg, tg/tg(la), and tg(la)/tg(la) mice. Analysis of grain density over individual Purkinje cells showed significantly greater concentrations of TH mRNA in tg/tg, tg/tg(la), and tg(la)/tg(la) mice as compared to +/+ wild type control mice. Comparison of adult (greater-than-or-equal-to 2 months) and young, pre-seizure (less-than-or-equal-to 3 weeks) mutant mice showed Purkinje cells densely labelled for TH mRNA at both ages, suggesting that TH gene expression in Purkinje cells is independent of the onset of seizures. Northern blot analysis confirmed the findings from the in situ hybridization studies, demonstrating a single band identical to TH mRNA. Immunohistochemistry confirmed the presence of TH protein in Purkinje cells of the caudal vermis and the lateral hemispheres of the cerebellum in both control and mutant mice. Quantitation of mRNA for TH and the coexisting neuropeptide, galanin, in the locus coeruleus detected no significant differences between adult tg/tg, tg/tg(la) and +/+ control mice. The present findings demonstrate that the classically GABAergic Purkinje cells in the cerebellum express low levels of TH, and that the mutant tottering and leaner strains of mice express extremely high levels of mRNA and protein for TH. C1 NIMH,BEHAV NEUROPHARMACOL UNIT,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NIMH,MOLEC PHARMACOL SECT,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. UNIV ILLINOIS,COLL VET MED,DEPT VET BIOSCI,URBANA,IL 61801. RI Schultzberg, Marianne/E-7076-2014 OI Schultzberg, Marianne/0000-0002-8314-0927 NR 41 TC 63 Z9 63 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 OCT PY 1992 VL 15 IS 3-4 BP 227 EP 240 DI 10.1016/0169-328X(92)90113-P PG 14 WC Neurosciences SC Neurosciences & Neurology GA JP584 UT WOS:A1992JP58400007 ER PT J AU ROSEN, JB CAIN, CJ WEISS, SRB POST, RM AF ROSEN, JB CAIN, CJ WEISS, SRB POST, RM TI ALTERATIONS IN MESSENGER-RNA OF ENKEPHALIN, DYNORPHIN AND THYROTROPIN-RELEASING-HORMONE DURING AMYGDALA KINDLING - AN INSITU HYBRIDIZATION STUDY SO MOLECULAR BRAIN RESEARCH LA English DT Article DE KINDLING; INSITU HYBRIDIZATION; ENKEPHALIN; DYNORPHIN; THYROTROPIN-RELEASING HORMONE; RNA; FOS ID ELECTROCONVULSIVE SHOCKS ALTER; RAT-BRAIN; C-FOS; ELECTRICAL STIMULATION; SUBSTANTIA NIGRA; SEIZURE ACTIVITY; MET-ENKEPHALIN; SPINAL-CORD; PRODYNORPHIN; PROENKEPHALIN AB The present study examined changes in mRNA expression of various neuropeptides at several stages of amygdala kindled seizures. S-35-labelled oligonucleotide probes for mRNA of enkephalin (ENK), dynorphin (DYN) and thyrotropin releasing hormone (TRH) were hybridized to brain sections of rats sacrificed 24 h after a stage 1 or stage 5 seizure, or 2 weeks after a stage 5 seizure. Changes in expression developed as kindling progressed, with long-lasting changes in ENK and transient changes in DYN and TRH. ENK mRNA levels increased in pyriform and entorhinal cortices at stage 1 and 5 and remained elevated in the pyriform two weeks after a stage 5 seizure. In contrast, DYN mRNA was decreased bilaterally in the dentate gyrus 24 h after a stage 5 seizure, but returned to control levels two weeks after a stage 5 seizure. TRH mRNA was dramatically increased 24 h after a stage 1 or stage 5 seizure. After a stage 1 seizure two patterns developed. One showed increases in the pyriform, entorhinal and perirhinal cortices ipsilateral to the stimulation. The other pattern displayed bilateral increases in the dentate gyrus with or without the unilateral increases the limbic cortices. Twenty-four hours after a stage 5 seizure, large bilateral increases were found in these areas, but these returned to baseline levels by two weeks after a stage 5 seizure. The data demonstrate a constellation of alterations in several peptide systems with distinct spatiotemporal patterns, particularly in regions known to be important in kindling and epilepsy, such as the dentate gyrus and pyriform and entorhinal cortices. The relationship of these neuropeptide mRNA changes to those previously found in c-fos mRNA expression during the development of kindling is discussed. RP ROSEN, JB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 51 TC 79 Z9 79 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 OCT PY 1992 VL 15 IS 3-4 BP 247 EP 255 DI 10.1016/0169-328X(92)90115-R PG 9 WC Neurosciences SC Neurosciences & Neurology GA JP584 UT WOS:A1992JP58400009 ER PT J AU HARRIS, AL WALTER, A PAUL, D GOODENOUGH, DA ZIMMERBERG, J AF HARRIS, AL WALTER, A PAUL, D GOODENOUGH, DA ZIMMERBERG, J TI ION CHANNELS IN SINGLE BILAYERS INDUCED BY RAT CONNEXIN32 SO MOLECULAR BRAIN RESEARCH LA English DT Article DE ION CHANNEL RECONSTITUTION; GAP JUNCTION; CONNEXIN; LIPID BILAYER; LIPOSOME; TRANSPORT-SPECIFIC FRACTIONATION ID GAP JUNCTION PROTEIN; PHOSPHOLIPID-VESICLES; PLANAR MEMBRANE; PLASMA-MEMBRANE; LIPID BILAYERS; VOLUME CHANGES; LIVER; LENS; CELLS; CONDUCTANCE AB The gap junction channel mediates an important form of intercellular communication, but its detailed study is hindered by inaccessibility in situ. We show here that connexin32, the major protein composing junctional channels in rat liver, forms ion channels in single bilayer membranes. The properties of these reconstituted connexin32 channels are characterized and compared with those of gap junction channels. The demonstration that connexin32 forms channels in single membranes has implications for assembly and regulation of junctional channels, and permits detailed study of the gating, permeability and modulation of this channel-forming protein. C1 WRIGHT STATE UNIV,DEPT PHYSIOL & BIOPHYS,DAYTON,OH 45435. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT ANAT & CELL BIOL,BOSTON,MA 02115. NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. RP HARRIS, AL (reprint author), JOHNS HOPKINS UNIV,THOMAS C JENKINS DEPT BIOPHYS,BALTIMORE,MD 21218, USA. FU NIGMS NIH HHS [GM36044, GM18974, GM37751] NR 82 TC 32 Z9 33 U1 0 U2 2 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 OCT PY 1992 VL 15 IS 3-4 BP 269 EP 280 DI 10.1016/0169-328X(92)90118-U PG 12 WC Neurosciences SC Neurosciences & Neurology GA JP584 UT WOS:A1992JP58400012 PM 1279354 ER PT J AU JOHNSON, G GOTLIB, J HAROUTUNIAN, V BIERER, L NAIRN, AC MERRIL, C WALLACE, W AF JOHNSON, G GOTLIB, J HAROUTUNIAN, V BIERER, L NAIRN, AC MERRIL, C WALLACE, W TI INCREASED PHOSPHORYLATION OF ELONGATION FACTOR-II IN ALZHEIMERS-DISEASE SO MOLECULAR BRAIN RESEARCH LA English DT Article DE PHOSPHORYLATION; ELONGATION FACTOR-II; ALZHEIMERS DISEASE; PHOSPHOPROTEIN ID MESSENGER-RNA TRANSLATION; PROTEIN KINASE-III; INVITRO PHOSPHORYLATION; MAMMALIAN-CELLS; BRAIN; INITIATION; TISSUES; BIOSYNTHESIS; DROSOPHILA; INFECTION AB Elongation factor 2 (EF-2) is a phosphoprotein that mediates the translocation step of elongation during protein synthesis. We investigated its phosphorylation to characterize translational regulation of gene expression in Alzheimer's disease. EF-2 was identified on two-dimensional (2D) gels of brain homogenates by analyzing immunoblots with EF-2-specific antibody (M(r) 96,000; pI 6.8). Four distinct charge variant isoforms were observed. We identified the two most acidic isoforms as being the phosphorylated forms by incorporation of radiolabeled phosphate. The phosphorylation of EF-2 in control and Alzheimer's disease (AD) brain was directly measured as the distribution of the four polypeptides on silver stained 2D gels. The ratio of the phosphorylated forms to unphosphorylated forms was elevated 45% in AD homogenates compared to controls (1.07+/-0.18; n = 9 vs 0.73+/-0.20; n = 6; P < 0.004) which indicated an increased phosphorylation of AD EF-2. The phosphorylation exhibited specificity to the disease in that it was observed in affected areas (cortex and hippocampus) but not in an unaffected area (thalamus) of the same brains. Because phosphorylation of EF-2 inhibits protein synthesis, the observed AD-associated phosphorylation of EF-2 is consistent with the reduced in vitro activity of polysomes isolated from AD tissues that we have previously reported. C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,MACK LAB,1 GUSTAVE LEVY PL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,ARTHUR M FISHBERG CTR NEUROBIOL,NEW YORK,NY 10029. ST ELIZABETH HOSP,NIMH,BIOCHEM GENET LAB,WASHINGTON,DC 20032. ROCKEFELLER UNIV,MOLEC & CELLULAR NEUROSCI LAB,NEW YORK,NY 10021. NR 46 TC 6 Z9 6 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 OCT PY 1992 VL 15 IS 3-4 BP 319 EP 326 DI 10.1016/0169-328X(92)90124-T PG 8 WC Neurosciences SC Neurosciences & Neurology GA JP584 UT WOS:A1992JP58400018 ER PT J AU WERNER, H BACH, MA STANNARD, B ROBERTS, CT LEROITH, D AF WERNER, H BACH, MA STANNARD, B ROBERTS, CT LEROITH, D TI STRUCTURAL AND FUNCTIONAL-ANALYSIS OF THE INSULIN-LIKE GROWTH FACTOR-I RECEPTOR GENE PROMOTER SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN-BREAST-CANCER; I IGF-I; TRANSCRIPTION FACTOR; DNA-BINDING; CELL-LINE; EXPRESSION; SP1; ACTIVATION; INVITRO; REGION AB The insulin-like growth factor I receptor (IGF-I-R) gene is expressed in most body tissues. The levels of IGF-I-R mRNA, however, are regulated by a number of physiological conditions (development, differentiation, and hormonal milieu) as well as in certain pathological states (diabetes and tumors). To understand the molecular mechanisms which control the transcription of the IGF-I-R gene, we have cloned the promoter of the rat receptor gene and have characterized its activity by transient expression assays. Different fragments of the 5'-flanking region (subcloned upstream of a luciferase reporter gene) were transfected into buffalo rat liver 3A cells (a cell line with a low number of IGF-I binding sites) and Chinese hamster ovary cells (a cell line with a higher number of cell-surface receptors). In both cell lines, most of the promoter activity was located in the proximal 416 base pairs of 5'-flanking region. However, further dissection of this proximal fragment revealed a cell type-specific pattern of promoter activity. Thus, in buffalo rat liver 3A cells, subfragments of this region each contributed to total activity, suggesting that contiguous cis-elements can act together to activate transcription. In Chinese hamster ovary cells, on the other hand, subfragments of the proximal promoter region partially substituted for the proximal 416 base pairs of 5'-flanking region. Coexpression studies using an IGF-I-R promoter reporter construct together with an Spl expression vector (under the control of an ADH promoter) were performed in SL2 cells, a Drosophila cell line which lacks endogenous Spl. The results obtained showed that Spl can trans-activate the IGF-I-R promoter in vivo. Transient transfection assays were complemented with gel-retardation assays and DNase I footprinting experiments, which showed that transcription factor Spl is potentially an important regulator of IGF-I-R gene expression. RP WERNER, H (reprint author), NIDDKD, DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT, 9000 ROCKVILLE PIKE,BLDG 10, ROOM 85243, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 NR 43 TC 86 Z9 88 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 OCT PY 1992 VL 6 IS 10 BP 1545 EP 1558 DI 10.1210/me.6.10.1545 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JV676 UT WOS:A1992JV67600003 PM 1448110 ER PT J AU IKUYAMA, S SHIMURA, H HOEFFLER, JP KOHN, LD AF IKUYAMA, S SHIMURA, H HOEFFLER, JP KOHN, LD TI ROLE OF THE CYCLIC ADENOSINE-3', 5'-MONOPHOSPHATE RESPONSE ELEMENT IN EFFICIENT EXPRESSION OF THE RAT THYROTROPIN RECEPTOR PROMOTER SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; PROGESTIN BIOSYNTHETIC CAPACITY; SOMATOMEDIN-C SYNERGIZES; GRANULOSA-CELLS; BINDING PROTEIN; TRANSCRIPTION FACTORS; SOMATOSTATIN GENE; MESSENGER-RNA; AMP; DNA AB The "minimal" promoter region of the TSH receptor gene, -195 to -39 basepairs (bp), exhibits basal promoter activity, thyroid specificity, and negative regulation by TSH via its cAMP signal. In FRT thyroid cells and by comparison to pTRCAT5'-199, 5'-deletion mutants of chloramphenicol acetyltransferase (CAT) constructs from -199 to -150 bp of the minimal promoter decrease basal CAT activity by 50%, whereas continued deletion to -146 bp increases activity more than 4-fold. Continued deletion to -131 bp results in basal activity less than that of the -199 bp construct. An octameric cAMP response element (CRE)-like sequence, TGAGGTCA, is within -146 to -131 bp and starts at -139 bp. Its mutation to a consensus CRE (TGACGTCA) or AP1 (TGAGTCA) site or mutation of several residues flanking its 3'-terminus can improve promoter activity as much as 8-fold compared to pTRCAT5'-199. A nonpalindromic mutation to CGAGGACA decreases basal promoter activity to the level of the 199-bp minimal promoter. The CRE-like sequence between -139 and -132 bp is a constitutive enhancer of promoter activity in FRT thyroid cells, since, ligated to a simian virus-40-promoter-driven CAT gene, it increases CAT activity in the absence of forskolin in proportion to copy number and independent of direction or position. It can, however, function as a cAMP-responsive CRE, as evidenced by the fact that forskolin increases the activity of the same simian virus-40-promoter-driven CAT gene constructs in Buffalo rat liver (BRL) cells. DNAase-I footprinting shows that the CRE region is protected by a purified binding region peptide of the CRE-binding protein, activating transcription factor-2, and recombinant AP1 (human c-jun) as well as by BRL, FRT, and FRTL-5 rat thyroid cell nuclear extracts. Gel mobility shift analyses show that multiple CRE-binding proteins in the BRL, FRT, and FRTL-5 cell nuclear extracts form complexes with the CRE-like site, that one of these is CRE-binding protein, and that all form complexes with mutant sequences of the CRE-like site in a manner that exactly parallels their effects on constitutive enhancer function in FRT thyroid cells. We show, therefore, that the CRE-like site in the minimal TSH receptor promoter functions as a constitutive enhancer of promoter activity in FRT thyroid cells yet is a cAMP-responsive CRE. We suggest that failure of the CRE-like site to act as a cAMP-inducible enhancer in FRT thyroid cells may relate to the ability of forskolin to cause negative regulation of the TSH receptor promoter in thyroid cells. Consistent with this, we show that sequences 3' to the CRE are important for cAMP-induced negative regulation of the TSH receptor minimal promoter. Thus, negative regulation by forskolin is evident in pTRCAT5'-131, which lacks the CRE site, and can be demonstrated with pTRCAT5'-146NP, the nonpalindromic mutant whose sequence loses enhancer activity and exhibits no specific interactions with CRE-binding nuclear proteins in FRTL-5, FRT, or BRL extracts. Activity is evident in FRT thyroid, but not BRL, cells and is expressed with a homologous, but not a heterologous, promoter, i.e. is thyroid and promoter specific in its expression. In addition to the sequences 3' to the CRE, which are important for cAMP-induced negative regulation of the TSH receptor minimal promoter, we show that a decanucleotide tandem repeat sequence immediately 5' to the CRE is a repressive element of constitutive CRE enhancer activity. Its repressive activity also appears to be thyroid specific, since it is expressed in FRT thyroid, but not BRL, cells. C1 NIDDKD, LAB BIOCHEM & METAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. UNIV COLORADO, CTR HLTH, DIV MED ONCOL, DENVER, CO 80262 USA. NR 42 TC 55 Z9 55 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 OCT PY 1992 VL 6 IS 10 BP 1701 EP 1715 DI 10.1210/me.6.10.1701 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JV676 UT WOS:A1992JV67600018 PM 1333054 ER PT J AU ROSA, PA SCHWAN, T HOGAN, D AF ROSA, PA SCHWAN, T HOGAN, D TI RECOMBINATION BETWEEN GENES ENCODING MAJOR OUTER SURFACE PROTEIN-A AND PROTEIN-B OF BORRELIA-BURGDORFERI SO MOLECULAR MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; LYME-DISEASE SPIROCHETE; ANTIGENIC VARIATION; ENZYMATIC AMPLIFICATION; MONOCLONAL-ANTIBODY; MOLECULAR ANALYSIS; DNA; HERMSII; INFECTION; AGENT AB Borrelia burgdorferi causes Lyme disease, a multisystem illness that can persist in humans for many years. We describe recombination between homologous genes encoding the major outer surface proteins (Osps) A and B of B. burgdorferi which both deletes osp gene sequences and creates chimaeric gene fusions. Recombinant osp genes occur in multiple strains and encode unique proteins that lack some characteristic Osp epitopes. Antigenic variation in Osp through recombination may be relevant to the persistence of B. burgdorferi in an infected host, and has important implications for the utility of OspA and OspB as diagnostic or vaccine candidates for Lyme disease. We also describe Osp variation arising from nonsense mutations and sequence divergence, which may also represent significant sources of Osp polymorphism. C1 NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. RP ROSA, PA (reprint author), NIAID,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 45 TC 124 Z9 125 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1992 VL 6 IS 20 BP 3031 EP 3040 DI 10.1111/j.1365-2958.1992.tb01761.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA JV234 UT WOS:A1992JV23400014 PM 1479892 ER PT J AU BENVENISTE, M MAYER, ML AF BENVENISTE, M MAYER, ML TI EFFECT OF EXTRACELLULAR PH ON THE POTENCY OF N-METHYL-DEUTERIUM-ASPARTIC ACID RECEPTOR COMPETITIVE ANTAGONISTS SO MOLECULAR PHARMACOLOGY LA English DT Article ID CULTURED HIPPOCAMPAL-NEURONS; RAT-BRAIN MEMBRANES; NMDA ANTAGONISTS; BINDING; PHARMACOLOGY; INHIBITION; GLYCINE; DESENSITIZATION; MODULATION; CHANNELS AB Structure-activity analysis reveals that acidic alpha-amino acids containing an omega-PO3H2 group are more potent antagonists at N-methyl-D-aspartate (NMDA) receptors than are analogs with omega-COOH or omega-tetrazole groups. At physiological values of extracellular pH the omega-PO3H2 group is only partially deprotonated and the corresponding antagonists exist as ions with one or two negative charges. In contrast, competitive antagonists with omega-COOH and omega-tetrazole groups are fully ionized at physiological pH but carry only a single negative charge. Dose-inhibition analysis was performed with (2R)-AP7 and its piperidine derivative LY 257883 to determine whether ionization of the omega-PO3H2 group influences NMDA receptor antagonist potency; these experiments revealed a >3-fold increase in potency on raising of the extracellular pH from 7.3 to pH 8.2, consistent with the increase in the relative concentration of the ionic form of the antagonist in which the omega-PO3H2 group contains two negative charges. Experiments with the omega-COOH-containing analog of LY 257883 and with SDZ EAB 515, an omega-PO3H2-containing antagonist of novel structure, revealed only 1.5- and 1.3-fold increases in potency, respectively, over the same pH range. Analysis of the kinetics of block of NMDA-activated currents resulting from rapid application of LY 257883 suggests that the increase in potency on raising of the extracellular pH results largely from an increase in the antagonist association rate constant but also from a small decrease in the dissociation rate constant. Together, these results suggest that the fully ionized forms of the R-enantiomers of AP7 and LY 257883 act as the active antagonist species at NMDA receptors. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BLDG 36,ROOM 2A21,BETHESDA,MD 20892. RI Mayer, Mark/H-5500-2013 NR 33 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1992 VL 42 IS 4 BP 679 EP 686 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JU460 UT WOS:A1992JU46000020 PM 1435743 ER PT J AU KUMAGAI, Y LIN, LY PHILPOT, RM YAMADA, H OGURI, K YOSHIMURA, H CHO, AK AF KUMAGAI, Y LIN, LY PHILPOT, RM YAMADA, H OGURI, K YOSHIMURA, H CHO, AK TI REGIOCHEMICAL DIFFERENCES IN CYTOCHROME-P450 ISOZYMES RESPONSIBLE FOR THE OXIDATION OF METHYLENEDIOXYPHENYL GROUPS BY RABBIT LIVER SO MOLECULAR PHARMACOLOGY LA English DT Article ID MONO-OXYGENASE SYSTEM; MICROSOMAL CYTOCHROME-P-450; HEPATIC CYTOCHROME-P-450; (METHYLENEDIOXY)PHENYL COMPOUNDS; MAJOR CYTOCHROME-P-450; CONSTITUTIVE FORMS; METABOLISM; PULMONARY; PURIFICATION; RAT AB The cytochrome P450 isozymes catalyzing the oxidation of the methylenedioxyphenyl compounds methylenedioxybenzene (MDB) and methylenedioxyamphetamine (MDA) have been investigated in rabbit liver preparations. The aromatic ring in MDB undergoes both demethylenation to catechol and aromatic hydroxylation to sesamol, whereas that in MDA undergoes only demethylenation to dihydroxyamphetamine. Formation of catechol and sesamol from MDB in microsomal incubation mixtures was enhanced about 5- and 3-fold, respectively, by pretreatment of the rabbits with phenobarbital, which induced CYP2B4 and CYP4B1. The cytochrome P450 isozyme responsible for aromatic hydroxylation of MDB was induced by beta-naphthoflavone and was inhibited by alpha-naphthoflavone. Microsomal demethylenation of MDA was minimally sensitive to pretreatment of the rabbits with phenobarbital,beta-naphthoflavone, pyrazole, or rifampicin. However, MDA competitively inhibited the N-demethylation of erythromycin. Antibodies against CYP2B4, but not those against CYP4B1, caused a marked inhibition of the demethylenation and aromatic hydroxylation of MDB. Antibodies against CYP2C3 did not inhibit the demethylenation of MDA, nor did substrates or inhibitors of the CYP2D family except for bufuralol. MDB and MDA were both capable of forming metabolic intermediate complexes, and the rate of complex formation was accelerated by phenobarbital induction. Reconstitution experiments with CYP2B4 suggested that phenobarbital-inducible complex formation from MDA was not due to the carbene pathway involving the methylenedioxy group but was due to oxidation of the amino group. These results indicate that CYP2B4 oxidizes different regions of methylenedioxyphenyl compounds depending on their structure. MDB undergoes oxidation at the methylenedioxy group (major) and the benzene ring (minor). MDA is oxidized at the alkylamino side chain at the nitrogen and alpha-carbon. The results suggested that one or more constitutive isoforms (probably unknown) of cytochrome P450 present in rabbit liver microsomes are primarily responsible for MDA demethylenation but that CYP3A6 contributes slightly. C1 UNIV CALIF LOS ANGELES,SCH MED,CTR HLTH SCI,DEPT PHARMACOL,LOS ANGELES,CA 90024. KYUSHU UNIV 62,FAC PHARMACEUT SCI,HIGASHI KU,FUKUOKA 812,JAPAN. NIEHS,RES TRIANGLE PK,NC 27709. FU NIDA NIH HHS [DA 04206] NR 59 TC 14 Z9 14 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1992 VL 42 IS 4 BP 695 EP 702 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JU460 UT WOS:A1992JU46000022 PM 1435745 ER PT J AU KADIISKA, MB HANNA, PM HERNANDEZ, L MASON, RP AF KADIISKA, MB HANNA, PM HERNANDEZ, L MASON, RP TI INVIVO EVIDENCE OF HYDROXYL RADICAL FORMATION AFTER ACUTE COPPER AND ASCORBIC-ACID INTAKE - ELECTRON-SPIN-RESONANCE SPIN-TRAPPING INVESTIGATION SO MOLECULAR PHARMACOLOGY LA English DT Article ID VITAMIN-C; BIOLOGICAL DAMAGE; TRANSITION-METALS; AQUEOUS-SOLUTION; RAT-LIVER; SUPEROXIDE; GENERATION; MECHANISM; TOXICITY; IRON AB Copper has been suggested to facilitate oxidative tissue injury through a free radical-mediated pathway analogous to the Fenton reaction. By applying the ESR spin-trapping technique, evidence for hydroxyl radical formation in vivo was obtained in rats treated simultaneously with copper and ascorbic acid. A secondary radical spin-trapping technique was used in which the hydroxyl radical formed the methyl radical upon reaction with dimethylsulfoxide. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap phenyl-N-t-butylnitrone (PBN). Because copper excreted into the bile from treated animals is expected to be maintained in the Cu(I) state (by ascorbic acid or glutathione), a chelating agent that would redox-stabilize it in the Cu(I) state was used to prevent ex vivo redox chemistry. Bile samples were collected directly into solutions of bathocuproinedisulfonic acid, a Cu(II)-stabilizing agent, and 2,2'-dipyridyl, a Fe(II)-stabilizing agent. If these precautions were not taken, radical adducts were generated ex vivo and could be mistaken for radical adducts generated in vivo and excreted into the bile. Besides the PBN/.CH3 adduct, three other radical adducts were produced in vivo and excreted in bile. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. BULGARIAN ACAD SCI,INST PHYSIOL,BU-1113 SOFIA,BULGARIA. NR 49 TC 72 Z9 73 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1992 VL 42 IS 4 BP 723 EP 729 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JU460 UT WOS:A1992JU46000026 PM 1331758 ER PT J AU FREIREICH, EJ AF FREIREICH, EJ TI IMPACT OF CYTOGENETICS AND MOLECULAR-GENETICS ON LEUKEMIA THERAPY SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT SYMP ON HUMAN CANCER : FROM PRECURABLE TO CURABLE, COMMEMORATING THE 65TH BIRTHDAY OF JAMES F HOLLAND CY MAY 29, 1990 CL MT SINAI MED CTR, NEW YORK, NY SP DERALD H RUTTENBERG, MR & MRS MARIO ASTADI, CRIT CARE AMER, SANDOZ PHARM, BRISTOL LABS, MEAD JOHNSON, SCHERING, UPJOHN, KNOL PHARM, ADRIA LABS HO MT SINAI MED CTR ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE MYELOMONOCYTIC LEUKEMIA; PATTERN C1 NCI,BETHESDA,MD 20892. RP FREIREICH, EJ (reprint author), UNIV TEXAS,ADULT LEUKEMIA RES PROGRAM,BOX 55,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD OCT PY 1992 VL 59 IS 5 BP 396 EP 399 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA JU588 UT WOS:A1992JU58800008 PM 1435834 ER PT J AU ZELAZOWSKI, P SMITH, MA GOLD, PW CHROUSOS, GP WILDER, RL STERNBERG, EM AF ZELAZOWSKI, P SMITH, MA GOLD, PW CHROUSOS, GP WILDER, RL STERNBERG, EM TI INVITRO REGULATION OF PITUITARY ACTH-SECRETION IN INFLAMMATORY DISEASE SUSCEPTIBLE LEWIS (LEW/N) AND INFLAMMATORY DISEASE RESISTANT FISCHER (F344/N) RATS SO NEUROENDOCRINOLOGY LA English DT Article DE CORTICOSTERONE; HYPOTHALAMIC-PITUITARY-ADRENAL AXIS; LEWIS RAT; FISCHER RAT ID CORTICOTROPIN-RELEASING-FACTOR; WALL-INDUCED ARTHRITIS; ANTERIOR-PITUITARY; CELLS; INTERLEUKIN-1; GLUCOCORTICOIDS; EXPRESSION; INSITU; AXIS; GENE AB We have previously shown that susceptibility to inflammatory disease in Lewis (LEW/N) rats is related to their limited hypothalamic-pituitary-adrenal (HPA) axis responses to a variety of inflammatory stimuli, while the relative resistance to inflammatory disease in Fischer (F344/N) rats is related to their potent HPA axis responses to these same stimuli. In vivo studies also showed that LEW/N pituitary ACTH responses to exogenous corticotropin-releasing hormone (CRH) were blunted compared to F344/N. To determine if there is a fundamental difference in pituitary corticotroph function between the two strains, independent of other factors influencing the HPA axis, we compared ACTH responses to a variety of stimuli in LEW/N and F344/N primary pituitary cell cultures. Here we show that in vitro basal ACTH secretion and peak ACTH response to CRH, forskolin and 8-bromo-cAMP are 50% lower in LEW/N than F344/N rats. However, these findings can be explained by other observations: diminished basal ACTH content, POMC mRNA, and a decreased number of corticotrophs, in pituitary cell cultures from LEW/N compared to F344/N rats. In addition, LEW/N corticotrophs were more sensitive to dexamethasone and to corticosterone suppression of CRH-stimulated ACTH secretion compared to F344/N. The data support the possibility of an HPA axis defect in LEW/N rats at the pituitary level which could be secondary to prolonged understimulation by hypothalamic CRH, or could also be partially related to enhanced glucocorticoid feedback inhibition. C1 NICHHD,PEDIAT ENDOCRINOL BRANCH,BETHESDA,MD. NIMH,NIAMS,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. RP ZELAZOWSKI, P (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NEUROENDOCRINE IMMUNOL & BEHAV UNIT,BETHESDA,MD 20892, USA. NR 26 TC 29 Z9 29 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD OCT PY 1992 VL 56 IS 4 BP 474 EP 482 DI 10.1159/000126264 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA KA640 UT WOS:A1992KA64000005 PM 1335552 ER PT J AU LOPEZ, JF PALKOVITS, M ARATO, M MANSOUR, A AKIL, H WATSON, SJ AF LOPEZ, JF PALKOVITS, M ARATO, M MANSOUR, A AKIL, H WATSON, SJ TI LOCALIZATION AND QUANTIFICATION OF PROOPIOMELANOCORTIN MESSENGER-RNA AND GLUCOCORTICOID RECEPTOR MESSENGER-RNA IN PITUITARIES OF SUICIDE VICTIMS SO NEUROENDOCRINOLOGY LA English DT Article DE HPA AXIS; PROOPIOMELANOCORTIN; GLUCOCORTICOID RECEPTOR; GENE EXPRESSION; SUICIDE ID CORTICOTROPIN-RELEASING FACTOR; PROOPIOMELANOCORTIN GENE-EXPRESSION; BETA-ENDORPHIN; ANTERIOR-PITUITARY; RAT ANTERIOR; STRESS; ADRENOCORTICOTROPIN; CELLS; INTERMEDIATE; CYCLOPHILIN AB Suicidal behavior has been associated with hypothalamic-pituitary-adrenal overactivity in humans, as measured by increased corticosteroid secretion. To investigate whether this overactivity is reflected at the pituitary level, we have studied the localization of pro-opiomelanocortin (POMC) mRNA, and glucocorticoid receptor (GR) mRNA, in human anterior pituitaries, and quantified these messages relative to controls. Pituitaries from 7 suicide victims and 11 cardiac deaths were sectioned into 10-mum slides, stained with thionin and processed for in situ hybridization using a riboprobe complementary to human POMC mRNA. To correct for possible postmortem cell loss, hybridization with P1B15, a cDNA complementary to rat cyclophillin mRNA, was used in adjacent sections. POMC mRNA containing cells were found to be localized in clusters and were highly associated with corticotropin-releasing hormone (CRH) receptors. In contrast, GR mRNA containing cells were distributed through the pituitary, although areas of increased density were associated with POMC mRNA cells. Quantification with a computerized image analysis system revealed a 25% increase in POMC message in suicide victims. Analysis of the corticotrophic cell clumps showed that the suicide victims had higher POMC mRNA density per cell (p = 0.04) and larger corticotrophic cell size (p = 0.04) than the cardiac death victims. No differences in GR mRNA were detected between the two groups, although GR and POMC mRNA levels were highly and significantly correlated (r = 0.8, p < 0.001). There were no differences in P1B15 message between the two groups. We conclude that in situ hybridization is a useful tool to study gene regulation in human neuroendocrine tissue and that suicide victims show evidence of chronic hypothalamic-pituitary-adrenal axis activation. C1 UNIV MICHIGAN,DEPT PSYCHIAT,ANN ARBOR,MI 48109. SEMMELWEIS UNIV MED,SCH MED,DEPT ANAT 1,H-1085 BUDAPEST 8,HUNGARY. NATL INST NERVOUS & MENTAL HLTH,BUDAPEST,HUNGARY. HAMILTON PSYCHIAT HOSP,HAMILTON,ONTARIO,CANADA. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP LOPEZ, JF (reprint author), MENTAL HLTH INST,205 ZINA PITCHER PL,ANN ARBOR,MI 48109, USA. RI Palkovits, Miklos/F-2707-2013 FU NIMH NIH HHS [NIMH 422251] NR 49 TC 57 Z9 57 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD OCT PY 1992 VL 56 IS 4 BP 491 EP 501 DI 10.1159/000126266 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA KA640 UT WOS:A1992KA64000007 PM 1335553 ER PT J AU ASHIZAWA, T DUNNE, CJ DUBEL, JR PERRYMAN, MB EPSTEIN, HF BOERWINKLE, E HEJTMANCIK, JF AF ASHIZAWA, T DUNNE, CJ DUBEL, JR PERRYMAN, MB EPSTEIN, HF BOERWINKLE, E HEJTMANCIK, JF TI ANTICIPATION IN MYOTONIC-DYSTROPHY .1. STATISTICAL VERIFICATION BASED ON CLINICAL AND HAPLOTYPE FINDINGS SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-CII GENE; TIGHT LINKAGE; LOCUS; CHROMOSOME-19; DISEASE; QUEBEC; RISKS; NCOI AB To determine whether anticipation in myotonic dystrophy (DM) is a true biologic phenomenon or an artifact of ascertainment bias, we studied 201 members of nine DM kindreds, including 67 individuals with the clinical diagnosis of DM. Of 49 parent-child pairs in which both the parents and the children were clinically affected, the onset of DM occurred in an earlier decade of life in the child than the parent in 44 pairs and in the same decade in five pairs (p < 0.001). To eliminate direct ascertainment bias, we excluded nine pairs involving the index patients. Indirect ascertainment bias due to incomplete penetrance was unlikely, since 55% of the children of DM parents had DM. However, by haplotype analysis of restriction fragment length polymorphisms, we diagnosed DM in one of the 42 asymptomatic children of affected parents and excluded DM in twenty-eight. We estimated that patients with early-onset DM would have produced an additional 25 DM children if they had normal fertility and nuptiality. Assuming that the expected age-of-onset distribution occurs without anticipation in these 25, only seven would have had the onset of DM earlier than their parents. With the corrected result, the child would have been affected earlier than the parent in 53 pairs, and the parent would have been affected at the same age as or earlier than the child in 13 pairs (p < 0.001). Thus, the observed anticipation is unlikely to be totally attributable to ascertainment bias, suggesting the potential importance of biologic mechanisms. C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. UNIV TEXAS,HLTH SCI CTR,CTR GENET,HOUSTON,TX 77225. NEI,CTR GENET,BETHESDA,MD 20892. VET AFFAIRS MED CTR,HOUSTON,TX. RP ASHIZAWA, T (reprint author), BAYLOR COLL MED,DEPT NEUROL,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. NR 41 TC 44 Z9 45 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1992 VL 42 IS 10 BP 1871 EP 1877 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA JT854 UT WOS:A1992JT85400004 PM 1407565 ER PT J AU ASHIZAWA, T DUBEL, JR DUNNE, PW DUNNE, CJ FU, YH PIZZUTI, A CASKEY, CT BOERWINKLE, E PERRYMAN, MB EPSTEIN, HF HEJTMANCIK, JF AF ASHIZAWA, T DUBEL, JR DUNNE, PW DUNNE, CJ FU, YH PIZZUTI, A CASKEY, CT BOERWINKLE, E PERRYMAN, MB EPSTEIN, HF HEJTMANCIK, JF TI ANTICIPATION IN MYOTONIC-DYSTROPHY .2. COMPLEX RELATIONSHIPS BETWEEN CLINICAL FINDINGS AND STRUCTURE OF THE GCT REPEAT SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-CII GENE; TIGHT LINKAGE; CHROMOSOME-19; LOCUS; NCOI AB We studied the expansion of the GCT repeats within the myotonic dystrophy protein kinase gene in nine myotonic dystrophy (DM) kindreds. Southern blot and polymerase chain reaction analyses of the repeat region demonstrated the expansion in all 62 patients with the diagnosis of DM. Among 43 DM parent-child pairs, age of onset in the child was earlier than in the parent in 36 pairs, in the same decade as the parent in five, and undetermined in two. The clinical anticipation observed in the 36 pairs accompanied an increase in the fragment size in 32, a decrease in two, and no apparent change in two pairs. In the remaining pairs without documented clinical anticipation, the fragment size increased in four, decreased in two, and was apparently unchanged in one. Overall, the size of expansion showed an inverse correlation with the age of onset (p < 0.001). In all seven pairs in which the fragment did not increase in size, the affected parent was male. Two congenital DM children born to affected mothers had expanded DNA greater than 4.5 kb. The differences between parent and child in age of onset significantly correlated with the differences in the expansion size among father-child pairs (p < 0.001) but not mother-child pairs (p > 0.5). Our data suggest that the expansion of the GCT repeats plays an important role in anticipation although other factors, including the sex of the affected parent, may have significant effects on molecular mechanisms of anticipation. C1 VET AFFAIRS MED CTR,HOUSTON,TX. UNIV TEXAS,HLTH SCI CTR,CTR GENET,HOUSTON,TX 77225. NEI,CTR GENET,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT MED,CARDIOL SECT,HOUSTON,TX 77030. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. RP ASHIZAWA, T (reprint author), BAYLOR COLL MED,DEPT NEUROL,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. NR 31 TC 117 Z9 120 U1 2 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1992 VL 42 IS 10 BP 1877 EP 1883 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA JT854 UT WOS:A1992JT85400005 PM 1407566 ER PT J AU DECARLI, C HAXBY, JV GILLETTE, JA TEICHBERG, D RAPOPORT, SI SCHAPIRO, MB AF DECARLI, C HAXBY, JV GILLETTE, JA TEICHBERG, D RAPOPORT, SI SCHAPIRO, MB TI LONGITUDINAL CHANGES IN LATERAL VENTRICULAR VOLUME IN PATIENTS WITH DEMENTIA OF THE ALZHEIMER TYPE SO NEUROLOGY LA English DT Article ID TEMPORAL-LOBE; DISEASE; BRAIN; TOMOGRAPHY; ATROPHY; CT; DIAGNOSIS; AGES AB We determined the rates of lateral ventricular enlargement and decline in cognitive performance for 11 men and nine women with dementia of the Alzheimer type (DAT), and compared these rates with the same measures obtained for age-matched healthy controls (nine men and eight women). DAT patients, as a group, had only mild cognitive impairment at initial evaluation, and each patient was followed from 9 months to over 7 years with yearly evaluations. Six DAT patients had isolated memory impairment as their only cognitive deficit early in the course of the disease. The rate of total lateral ventricle enlargement (cm3/yr) was significantly different between DAT and healthy controls, and was more specific and sensitive to the diagnosis of DAT than comparison of cross-sectional volumes at final evaluation. The rate of total lateral ventricular enlargement did not differ significantly by patient sex, ventricular size at initial evaluation, age, or degree of cognitive impairment as measured by Mini Mental State Examination scores. However, in the six DAT patients initially found to have isolated memory impairment, the rate of ventricular enlargement during the period of isolated memory impairment was significantly less than the rate of ventricular enlargement after the onset of nonmemory cognitive impairment. The diagnostic power of total lateral ventricular measures made from two CTs separated by 1 year and obtained early in the course of the illness, however, was only 0.33. We conclude that the total lateral ventricular enlargement accompanying DAT is due to continuous, pathologic cell loss, significantly greater than cell loss due to the healthy aging process. The rate of total lateral ventricular enlargement very early in the course of Alzheimer's disease is significantly less than the rate of ventricular enlargement is after the onset of nonmemory cognitive deficits but is stable for all other degrees of dementia severity, suggesting a biphasic process. Although not diagnostic for the disease early in its course, longitudinal CT measures can still provide a reliable and independent measure of disease progression in patients with DAT. RP DECARLI, C (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009 NR 36 TC 69 Z9 70 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 OCT PY 1992 VL 42 IS 10 BP 2029 EP 2036 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA JT854 UT WOS:A1992JT85400029 PM 1407587 ER PT J AU GOLD, JM GOLDBERG, TE WEINBERGER, DR AF GOLD, JM GOLDBERG, TE WEINBERGER, DR TI PREFRONTAL FUNCTION AND SCHIZOPHRENIC SYMPTOMS SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE NEUROIMAGING; SUPERVISORY ATTENTION; HYPOFRONTALITY ID CARD SORTING TEST; CORTICAL BLOOD-FLOW; FRONTAL-LOBE; CEREBRAL-CORTEX; PHYSIOLOGICAL DYSFUNCTION; BRAIN PATHOLOGY; RHESUS-MONKEY; ABNORMALITIES; DOPAMINE; IMPAIRMENTS AB Neuroimaging and neuropsychological studies suggest that schizophrenia is a brain disease preferentially impairing frontal lobe function. Many of the cognitive and symptomatic abnormalities found in patients with schizophrenia resemble those found in patients with primary frontal lobe disease. Both groups of patients demonstrate abnormalities of behavior regulation that present as deactivation or disinhibition syndromes. Both groups also have striking cognitive deficits that are most apparent on tasks such as the Wisconsin Card Sort (WCS) that involve the switching of set and the integration of feedback in response planning. Regional cerebral blood flow studies demonstrate that patients with schizophrenia fail to normally activate prefrontal cortex during their performance of the WCS, providing convergent validity for the behavioral findings. This failure to activate dorsolateral prefrontal cortex may relate to ventricular enlargement and dopaminergic hypofunction. The latter finding is important because evidence from primate studies indicates that prefrontal cognitive performance is critically dependent upon the mesocortical dopamine system. Moreover, frontal lobe function may relate to limbic and striatal dopamine activity modulation. Thus, frontal dopamine dysfunction provides a model for the positive and negative symptoms of schizophrenia. Cognitive models of executive control processes allow for a differentiated approach to the nature of negative symptoms. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20003. NR 73 TC 31 Z9 31 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD OCT PY 1992 VL 5 IS 4 BP 253 EP 261 PG 9 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA JV294 UT WOS:A1992JV29400003 ER PT J AU KNUSEL, B RABIN, S WIDMER, HR HEFTI, F KAPLAN, DR AF KNUSEL, B RABIN, S WIDMER, HR HEFTI, F KAPLAN, DR TI NEUROTROPHIN-INDUCED TRK RECEPTOR PHOSPHORYLATION AND CHOLINERGIC NEURON RESPONSE IN PRIMARY CULTURES OF EMBRYONIC RAT-BRAIN NEURONS SO NEUROREPORT LA English DT Article DE NT-3; ERK1; MAP KINASE; PHOSPHOLIPASE-C-GAMMA-1; TYROSINE PHOSPHORYLATION; K-252B; PROTEIN KINASE INHIBITOR; BASAL FOREBRAIN CHOLINERGIC NEURONS; BRAIN CELL CULTURE; NERVE GROWTH FACTORS ID NERVE GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; KINASE-ACTIVITY; FAMILY; CELLS; NGF AB TYROSINE phosphorylation of trk type neurotrophin receptors in primary cultures of embryonic rat brain cells was studied by immunoprecipitation and immunoblotting. In cultures containing basal forebrain cholinergic neurons, but not in cultures of cerebral cortex, nerve growth factor (NGF) treatment for 4 min induced tyrosine phosphorylation of trk family proteins. Stimulation with brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3), resulted in a very robust phosphorylation signal in basal forebrain and cortical cultures, suggesting actions of these neurotrophins not only on cholinergic cells but probably on most embryonic brain neurons. Trk tyrosine phosphorylation was completely abolished by 5 muM K-252b. Inhibition was rapid, being evident by 30 s following addition of the drug. Corresponding stimulatory and inhibitory effects were seen for phospholipase-Cgamma1 (PLCgamma1) and extracellular signal-regulated kinase 1 (Erk1), two enzymes involved in second messenger mechanisms. Our findings indicate involvement of trk receptor activation in the NGF response of basal forebrain cholinergic cells and provide evidence for widespread presence of BDNF and NT-3 responsive neurons in the embryonic brain. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. RP KNUSEL, B (reprint author), UNIV SO CALIF,ETHEL PERCY ANDRUS GERONTOL CTR,LOS ANGELES,CA 90089, USA. FU NCI NIH HHS [N01-CO-74101]; NIA NIH HHS [AG14080]; NINDS NIH HHS [NS22933] NR 24 TC 36 Z9 36 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT PY 1992 VL 3 IS 10 BP 885 EP 888 PG 4 WC Neurosciences SC Neurosciences & Neurology GA JV072 UT WOS:A1992JV07200016 PM 1421094 ER PT J AU ROWLAND, AS BAIRD, DD WEINBERG, CR SHORE, DL SHY, CM WILCOX, AJ AF ROWLAND, AS BAIRD, DD WEINBERG, CR SHORE, DL SHY, CM WILCOX, AJ TI REDUCED FERTILITY AMONG WOMEN EMPLOYED AS DENTAL ASSISTANTS EXPOSED TO HIGH-LEVELS OF NITROUS-OXIDE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SPRAGUE-DAWLEY RATS; SPONTANEOUS-ABORTION; DELAYED CONCEPTION; CIGARETTE-SMOKING; ANESTHETIC-GASES; PREGNANCY; EXPOSURES; WORKPLACE; DENTISTS; TOXICITY AB Background. Fertility is reduced in female rats exposed to levels of nitrous oxide similar to those found in some dental offices. Epidemiologic studies have suggested an association between exposure to mixed anesthetic gases and impaired fertility. We investigated the effects of occupational exposure to nitrous oxide on the fertility of female dental assistants. Methods. Screening questionnaires were mailed to 7000 female dental assistants, ages 18 to 39, registered by the California Department of Consumer Affairs. Sixty-nine percent responded. Four hundred fifty-nine women were determined to be eligible, having become pregnant during the previous four years for reasons unrelated to the failure of birth control, and 91 percent of these women completed telephone interviews. Detailed information was collected on exposure to nitrous oxide and fertility (measured by the number of menstrual cycles without contraception that the women required to become pregnant). Results. After controlling for covariates, we found that women exposed to high levels of nitrous oxide were significantly less fertile than women who were unexposed or exposed to lower levels of nitrous oxide. The effect was evident only in the 19 women with five or more hours of exposure per week. These women were only 41 percent (95 percent confidence interval, 23 to 74 percent; P<0.003) as likely as unexposed women to conceive during each menstrual cycle. Conclusions. Occupational exposure to high levels of nitrous oxide may adversely affect a woman's ability to become pregnant. C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. RP ROWLAND, AS (reprint author), NIEHS,EPIDEMIOL BRANCH,A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 35 TC 195 Z9 196 U1 2 U2 8 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 1 PY 1992 VL 327 IS 14 BP 993 EP 997 DI 10.1056/NEJM199210013271405 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JQ225 UT WOS:A1992JQ22500005 PM 1298226 ER PT J AU FROHLICH, ED APSTEIN, C CHOBANIAN, AV DEVEREUX, RB DUSTAN, HP DZAU, V FAUADTARAZI, F HORAN, MJ MARCUS, M MASSIE, B PFEFFER, MA RE, RN ROCCELLA, EJ SAVAGE, D SHUB, C AF FROHLICH, ED APSTEIN, C CHOBANIAN, AV DEVEREUX, RB DUSTAN, HP DZAU, V FAUADTARAZI, F HORAN, MJ MARCUS, M MASSIE, B PFEFFER, MA RE, RN ROCCELLA, EJ SAVAGE, D SHUB, C TI MEDICAL PROGRESS - THE HEART IN HYPERTENSION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID LEFT-VENTRICULAR HYPERTROPHY; NORMAL CORONARY-ARTERIES; CARDIAC-HYPERTROPHY; BLOOD-PRESSURE; MYOCARDIAL HYPERTROPHY; SYSTEMIC HYPERTENSION; SUDDEN-DEATH; COMPUTED-TOMOGRAPHY; ANGINA-PECTORIS; GROWTH-FACTOR C1 BOSTON UNIV,SCH MED,BOSTON,MA 02118. NEW YORK HOSP,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. VET AFFAIRS MED CTR,BIRMINGHAM,AL. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. CLEVELAND CLIN EDUC FDN,CLEVELAND,OH 44106. NHLBI,BETHESDA,MD 20892. VET AFFAIRS MED CTR,SAN FRANCISCO,CA. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. RP FROHLICH, ED (reprint author), ALTON OCHSNER MED FDN & OCHSNER CLIN,1516 JEFFERSON HWY,NEW ORLEANS,LA 70121, USA. NR 176 TC 433 Z9 438 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 1 PY 1992 VL 327 IS 14 BP 998 EP 1008 DI 10.1056/NEJM199210013271406 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA JQ225 UT WOS:A1992JQ22500006 PM 1518549 ER PT J AU MILLER, FW LEITMAN, SF PLOTZ, PH AF MILLER, FW LEITMAN, SF PLOTZ, PH TI PLASMA-EXCHANGE IN POLYMYOSITIS AND DERMATOMYOSITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH,BETHESDA,MD 20892. RP MILLER, FW (reprint author), US FDA,WASHINGTON,DC 20204, USA. OI Miller, Frederick/0000-0003-2831-9593 NR 2 TC 0 Z9 0 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 OCT 1 PY 1992 VL 327 IS 14 BP 1030 EP 1031 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JQ225 UT WOS:A1992JQ22500018 ER PT J AU BERGSAGEL, PL TIMBLIN, CR ECKHARDT, L LASKOV, R KUEHL, WM AF BERGSAGEL, PL TIMBLIN, CR ECKHARDT, L LASKOV, R KUEHL, WM TI SEQUENCE AND EXPRESSION OF A MURINE CDNA-ENCODING PC326, A NOVEL GENE EXPRESSED IN PLASMACYTOMAS BUT NOT NORMAL PLASMA-CELLS SO ONCOGENE LA English DT Article ID TRANSLOCATED MYC GENE; C-MOS; SACCHAROMYCES-CEREVISIAE; MOUSE MYELOMA; BETA-SUBUNIT; G-PROTEIN; EXTINCTION; ONCOGENE; ENHANCER; HYBRIDS AB Using a subtractive cDNA approach we have identified a gene, PC326, expressed in 13 of 14 murine plasmacytoma cell lines, but not in any B- or pre-B-lymphoma cell lines. It expresses 4.6-kb and 5.2-kb mRNAs that encode a 747 amino acid protein containing two highly acidic domains flanking a novel, moderately acidic 20 amino acid sequence that is repeated 7.5 times. Sequence comparison identifies an additional 43 amino acid domain that is homologous to a repeated sequence found in the members of the beta-transducin gene family. The PC326 mRNA is detectable in testis but in no other murine tissues, including plasma cells induced by lipopolysaccharide stimulation of splenocytes. Somatic cell hybrids derived from plasmacytomas and fibroblast or T-cell lines have a fibroblastic or T-cell phenotype respectively. Unlike B-cell-specific genes (e.g. immunoglobulin), the expression of which is extinguished in these hybrids, PC326 mRNA appears to be irreversibly turned on in these hybrids. Since PC326 is not expressed in normal plasma cells, it appears that its expression is a cause or consequence of the tumorigenic process that generates murine plasmacytomas. C1 NCI, USN, MED ONCOL BRANCH, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. COLUMBIA UNIV, DEPT BIOL SCI, NEW YORK, NY 10027 USA. HEBREW UNIV JERUSALEM, HADASSAH MED SCH, HUBERT H HUMPHREY CTR EXPTL MED & CANC RES, IL-91010 JERUSALEM, ISRAEL. NR 39 TC 14 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD OCT PY 1992 VL 7 IS 10 BP 2059 EP 2064 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA JP424 UT WOS:A1992JP42400021 PM 1408147 ER PT J AU GRUNDFAST, KM SANAGUSTIN, TB AF GRUNDFAST, KM SANAGUSTIN, TB TI FINDING THE GENE(S) FOR WAARDENBURG SYNDROME(S) SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID SYNDROME TYPE-I; MOUSE; PAX-3 C1 GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. NIDCD,BETHESDA,MD. RP GRUNDFAST, KM (reprint author), CHILDRENS NATL MED CTR,DEPT OTOLARYNGOL,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 24 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 1992 VL 25 IS 5 BP 935 EP 951 PG 17 WC Otorhinolaryngology SC Otorhinolaryngology GA JR188 UT WOS:A1992JR18800006 PM 1408197 ER PT J AU LUDLOW, CL DOOMAN, AG AF LUDLOW, CL DOOMAN, AG TI GENETIC-ASPECTS OF IDIOPATHIC SPEECH AND LANGUAGE DISORDERS SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID SEX-CHROMOSOME ABNORMALITIES; FAMILY HISTORY; TOURETTE SYNDROME; UNSELECTED CHILDREN; IMPAIRED CHILDREN; MRI FINDINGS; TWIN PAIRS; TRANSMISSION; AGGREGATION; STUTTERERS RP LUDLOW, CL (reprint author), NIDCD,VOICE & SPEECH SECT,BLDG 10,ROOM 5D38,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 66 TC 10 Z9 10 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 1992 VL 25 IS 5 BP 979 EP 994 PG 16 WC Otorhinolaryngology SC Otorhinolaryngology GA JR188 UT WOS:A1992JR18800009 PM 1408200 ER PT J AU WILCOX, ER AF WILCOX, ER TI STRATEGIES FOR CONSTRUCTING A GUINEA-PIG ORGAN OF CORTI CDNA LIBRARY AND ITS POTENTIAL USE SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PROTEINS RP WILCOX, ER (reprint author), NIDCD,MOLEC BIOL LAB,BLDG 36,ROOM 5D-08,BETHESDA,MD 20892, USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 1992 VL 25 IS 5 BP 1011 EP 1016 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA JR188 UT WOS:A1992JR18800011 PM 1408189 ER PT J AU HUNTER, C DOI, K WENTHOLD, RJ AF HUNTER, C DOI, K WENTHOLD, RJ TI NEUROTRANSMISSION IN THE AUDITORY-SYSTEM SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID GUINEA-PIG COCHLEA; CENTRAL-NERVOUS-SYSTEM; ENKEPHALIN-LIKE IMMUNOREACTIVITY; SUPERIOR OLIVARY COMPLEX; OUTER HAIR-CELLS; GLUTAMINASE-LIKE IMMUNOREACTIVITY; GLUTAMATE RECEPTOR SUBUNIT; TRANSMITTER AMINO-ACIDS; GAMMA-AMINOBUTYRIC ACID; BRAIN-STEM C1 OSAKA UNIV,DEPT PHYSIOL,OSAKA,JAPAN. RP HUNTER, C (reprint author), NIDCD,NEUROCHEM LAB,NEUROTRANSMITTER RECEPTOR BIOL SECT,BLDG 36,ROOM 5008,BETHESDA,MD 20892, USA. NR 211 TC 15 Z9 15 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 1992 VL 25 IS 5 BP 1027 EP 1052 PG 26 WC Otorhinolaryngology SC Otorhinolaryngology GA JR188 UT WOS:A1992JR18800013 PM 1357616 ER PT J AU SNOW, JB AF SNOW, JB TI MOLECULAR-BIOLOGY AND GENETICS - FOREWORD SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Editorial Material RP SNOW, JB (reprint author), NIDCD,BLDG 31,ROOM 3C02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 1992 VL 25 IS 5 BP R15 EP R16 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA JR188 UT WOS:A1992JR18800001 ER PT J AU ROBINSON, MB HEYES, MP ANEGAWA, NJ GORRY, E DJALI, S MELLITS, ED BATSHAW, ML AF ROBINSON, MB HEYES, MP ANEGAWA, NJ GORRY, E DJALI, S MELLITS, ED BATSHAW, ML TI QUINOLINATE IN BRAIN AND CEREBROSPINAL-FLUID IN RAT MODELS OF CONGENITAL HYPERAMMONEMIA SO PEDIATRIC RESEARCH LA English DT Article ID SEROTONIN TURNOVER; KYNURENIC ACID; AMINO-ACIDS; TRYPTOPHAN; MICE; QUANTIFICATION; UREASE; CHROMATOGRAPHY; METABOLITES; INCREASE AB Children with inborn errors of urea synthesis who survive neonatal hyperammonemic coma commonly exhibit cognitive deficits and neurologic abnormalities. Yet, there is evidence that ammonia is not the only neurotoxin. Hyperammonemia appears to induce a number of neurochemical alterations. In rodent models of hyperammonemia, uptake Of L-tryptophan into brain is increased. It has been reported that in an experimental rat model of hepatic encephalopathy, in the ammonium acetate-injected rat, and in patients with hepatic failure and inborn errors of ammonia metabolism, quinolinate, a tryptophan metabolite, is increased. Elevations in quinolinate are of particular concern, as quinolinate could excessively activate the N-methyl-D-aspartate subclass of excitatory amino acid receptors, thereby causing selective neuronal necrosis. We sought to identify an animal model that would replicate the increases in quinolinate that have been associated with hyperammonemia in humans. Levels of quinolinate were measured in hyperammonemic urease-infused rats and ammonium acetate-injected rats. In the urease-infused rat, brain tryptophan was doubled, and serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly increased. Yet, despite the increase in tryptophan and evidence for increased metabolism of tryptophan to serotonin, there were no observed increases of quinolinate in brain, cerebrospinal fluid, or plasma. In the ammonium acetate-injected rat, significant increases of 5-hydroxyindoleacetic acid in cerebral cortex were also observed, but quinolinate did not change in cerebrospinal fluid or cerebral cortex. In summary, we were unable to demonstrate an increase of quinolinate in brain or cerebrospinal fluid in these rat models of hyperammonemia. C1 NIMH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT NEUROL,BALTIMORE,MD 21205. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT NEUROL,PHILADELPHIA,PA 19104. RP ROBINSON, MB (reprint author), UNIV PENN,CHILDRENS HOSP PHILADELPHIA,SCH MED,CHILDRENS SEASHORE HOUSE,PHILADELPHIA,PA 19104, USA. FU NICHD NIH HHS [P30-HD-26979]; NINDS NIH HHS [R01-NS28033] NR 28 TC 23 Z9 23 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 OCT PY 1992 VL 32 IS 4 BP 483 EP 488 DI 10.1203/00006450-199210000-00021 PG 6 WC Pediatrics SC Pediatrics GA JQ385 UT WOS:A1992JQ38500021 PM 1279510 ER PT J AU SIDRANSKY, E SHERER, DM GINNS, EL AF SIDRANSKY, E SHERER, DM GINNS, EL TI GAUCHER DISEASE IN THE NEONATE - A DISTINCT GAUCHER PHENOTYPE IS ANALOGOUS TO A MOUSE MODEL CREATED BY TARGETED DISRUPTION OF THE GLUCOCEREBROSIDASE GENE SO PEDIATRIC RESEARCH LA English DT Note ID EMBRYONIC STEM-CELLS; HYDROPS FETALIS; MUTATIONS; HETEROGENEITY AB A group of neonates with Gaucher disease with a particularly devastating clinical course is described. The phenotype of these infants is analogous to that of a Gaucher mouse, which was created by targeted disruption of the mouse glucocerebroside gene. Similar to the homozygous mutant mice with glucocerebrosidase deficiency, these infants present at or shortly after birth, have rapidly progressing fulminant disease, and many have associated ichthyotic skin and/or hydrops fetalis. This transgenetic mouse model of Gaucher disease has helped us to appreciate a distinct Gaucher phenotype. Potentially, as this technology is applied to create other animal models of metabolic diseases, it may enable the recognition of other, as yet unappreciated presentations of inherited disorders. C1 STRONG MEM HOSP,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,ROCHESTER,NY 14642. RP SIDRANSKY, E (reprint author), NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BLDG 10,ROOM 3N256,9000,BETHESDA,MD 20892, USA. NR 30 TC 101 Z9 103 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 1992 VL 32 IS 4 BP 494 EP 498 DI 10.1203/00006450-199210000-00023 PG 5 WC Pediatrics SC Pediatrics GA JQ385 UT WOS:A1992JQ38500023 PM 1437405 ER PT J AU NIKBAKHT, KN LAWTON, MP PHILPOT, RM AF NIKBAKHT, KN LAWTON, MP PHILPOT, RM TI GUINEA-PIG OR RABBIT LUNG FLAVIN-CONTAINING MONOOXYGENASES WITH DISTINCT MOBILITIES IN SDS-PAGE ARE ALLELIC VARIANTS THAT DIFFER AT ONLY 2 POSITIONS SO PHARMACOGENETICS LA English DT Article AB Both guinea pig and rabbit express two variants of the 'lung' flavin-containing monooxygenase (FMO), observed as three distinct phenotypes based on mobility differences in SDS-PAGE. Samples of messenger RNA prepared from lungs of the two homozygous phenotypes of the guinea pig were used for the construction of two cDNA libraries. The libraries were screened with a cDNA encoding the rabbit lung FMO, and positive clones for each guinea pig lung FMO variant were isolated and sequenced. A full length clone from each library was found to encode a protein of 535 amino acids containing two pyrophosphate binding sites. Comparison of the sequences of the guinea pig and rabbit lung FMOs shows that their primary structures are 86% identical. The coding region sequences of the guinea pig variants differ at only two positions, and both differences result in amino acid substitutions. Sequence analysis has also been completed on a partially characterized variant of the rabbit lung FMO. As with the guinea pig, the nucleotide and amino acid sequences of the rabbit variants differ at only two positions. The cDNAs encoding the guinea pig variants were expressed in yeast. The activities of the enzymes are characteristic of the lung FMO, and the mobilities of the expressed enzymes are the same as those observed for the variants present in guinea pig pulmonary microsomal preparations. Similar to findings for the rabbit, analysis of genomic DNA indicates that the guinea pig lung FMO is associated with a single gene. The results of cDNA sequence analysis, expression in yeast, and analysis of genomic DNA indicate that the multiple lung FMOs in guinea pig and rabbit are allelic variants whose mobilities in SDS-PAGE are markedly altered by minimal changes in primary structure. C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. NR 0 TC 31 Z9 33 U1 1 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD OCT PY 1992 VL 2 IS 5 BP 207 EP 216 DI 10.1097/00008571-199210000-00003 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA LG855 UT WOS:A1992LG85500003 PM 1306120 ER PT J AU NEWLIN, DB WONG, CJ CHESKIN, LJ AF NEWLIN, DB WONG, CJ CHESKIN, LJ TI CARDIOVASCULAR-RESPONSES TO NALOXONE CHALLENGE IN OPIATE-DEPENDENT INDIVIDUALS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE NALOXONE; OPIATE WITHDRAWAL; HEART RATE; VAGAL TONE; PARASYMPATHETIC; SYMPATHETIC; ABUSED DRUGS ID FREELY MOVING RATS; PREFERENTIAL STIMULATION; NUCLEUS ACCUMBENS; DOPAMINE RELEASE; CATECHOLAMINES; WITHDRAWAL; ALCOHOL AB Vagally mediated tachycardia appears to be a common response to abused drugs and, therefore, has implications for abuse liability. To test the specificity of this common factor, we determined whether the tachycardia to naloxone in opiate-dependent individuals has a significant vagal component. Naloxone challenge (0.4 mg, IM) in 19 opiate-dependent men and women was associated with highly reliable tachycardia, but no significant change in vagal tone index, a noninvasive measure of parasympathetic inhibitory control of the heart. We conclude that tachycardia during naloxone-precipitated withdrawal is not vagally mediated. Thus, there is some degree of specificity to the common factor of vagally mediated tachycardia to abused drugs because it was ruled out in at least one drug (naloxone) with aversive subjective effects. RP NEWLIN, DB (reprint author), NIDA,ADDICT RES CTR,ETIOL BRANCH,BOX 5180,BALTIMORE,MD 21224, USA. NR 24 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD OCT PY 1992 VL 43 IS 2 BP 357 EP 360 DI 10.1016/0091-3057(92)90162-9 PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JQ387 UT WOS:A1992JQ38700005 PM 1332078 ER PT J AU RAO, CM ZIGLER, JS AF RAO, CM ZIGLER, JS TI LEVELS OF REDUCED PYRIDINE-NUCLEOTIDES AND LENS PHOTODAMAGE SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID METAL-CATALYZED OXIDATION; GUINEA-PIG LENS; ZETA-CRYSTALLIN; SINGLET OXYGEN; CATARACT FORMATION; ALPHA-CRYSTALLIN; AMINO-ACIDS; EYE LENS; TRYPTOPHAN; PROTEINS AB Since most of the known factors that are associated with cataract formation are oxidative in nature, one would expect that a highly reductive environment might arrest or retard the progress of cataract formation. Reduced nucleotides, both NADH and NADPH, are potent reductants with a large negative redox potential of - 320 mV. Lenses of certain species contain high levels of these nucleotides, presumably due to the presence of taxon specific crystallins. We have utilized this situation to investigate whether the levels of reduced pyridine nucleotides modulate photo-oxidative damage to the lens. We have monitored the time dependent loss of tryptophan fluorescence upon photodamage for lenses from guinea pig, rabbit and frog (Rana) that contain high levels of pyridine nucleotides and compared with the lenses from rat, Xenopus and a mutant strain of guinea pig that contain significantly lower amounts of these nucleotides. About 75% and 90% of the initial fluorescence intensity is lost in the case of rat and Xenopus lenses, respectively, after a total of 35 min exposure. Rabbit, guinea pig and frog lenses, under identical conditions, show only about 35-40% loss of the initial fluorescence. It appears that the lenses that contain high levels of reduced nucleotides are less susceptible to photodamage. The observed anti-oxidative role of reduced nucleotides in the lenses indicates the possibility of testing reductants (NADPH, NADH and their functional analogues) as potential candidates to therapeutically intervene in the process of cataractogenesis. RP RAO, CM (reprint author), NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892, USA. NR 44 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 1992 VL 56 IS 4 BP 523 EP 528 DI 10.1111/j.1751-1097.1992.tb02196.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JR355 UT WOS:A1992JR35500014 PM 1454882 ER PT J AU JOSHI, MK VANRENSEN, JJS BOSE, S AF JOSHI, MK VANRENSEN, JJS BOSE, S TI 4-CHLORO-5-(DIMETHYLAMINO)-2-PHENYL-3-(2H)-PYRIDAZINONE (SAN 9785) INDUCED CHANGES IN THE STRUCTURE AND FUNCTION OF THYLAKOID MEMBRANES OF PISUM-SATIVUM SO PHOTOSYNTHESIS RESEARCH LA English DT Meeting Abstract C1 JAWAHARLAL NEHRU UNIV,CBT,NEW DELHI 110067,INDIA. NIH,BETHESDA,MD 20892. AGR UNIV WAGENINGEN,DEPT PLANT PHYSIOL RES,6703 BW WAGENINGEN,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0166-8595 J9 PHOTOSYNTH RES JI Photosynth. Res. PD OCT PY 1992 VL 34 IS 1 BP 192 EP 192 PG 1 WC Plant Sciences SC Plant Sciences GA JV848 UT WOS:A1992JV84800563 ER PT J AU SHAPIRO, BY DAYAN, I GITTERMAN, M WEISS, GH AF SHAPIRO, BY DAYAN, I GITTERMAN, M WEISS, GH TI EXACT CALCULATION OF SHAPIRO STEP SIZES FOR PULSE-DRIVEN JOSEPHSON-JUNCTIONS SO PHYSICAL REVIEW B LA English DT Article AB A nonperturbative solution is presented for the current-voltage characteristics of Josephson junctions driven by square-wave and periodic delta-function signals. We find that no resonance conditions are required for the appearance of Shapiro steps-they appear for almost all amplitudes and frequencies of the driving pulse. Our calculations also permit a calculation of the boundaries of the Shapiro steps. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP SHAPIRO, BY (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. NR 14 TC 10 Z9 10 U1 1 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0163-1829 J9 PHYS REV B JI Phys. Rev. B PD OCT 1 PY 1992 VL 46 IS 13 BP 8349 EP 8352 DI 10.1103/PhysRevB.46.8349 PG 4 WC Physics, Condensed Matter SC Physics GA JT040 UT WOS:A1992JT04000048 ER PT J AU SHAPIRO, BY GITTERMAN, M DAYAN, I AF SHAPIRO, BY GITTERMAN, M DAYAN, I TI SHAPIRO STEPS IN THE FLUXON MOTION IN SUPERCONDUCTORS SO PHYSICAL REVIEW B LA English DT Article ID HIGH-TC SUPERCONDUCTORS; WEAK LINKS AB A method for studying the fluxon motion in superconductors is suggested based on so-called Shapiro steps in the current-voltage characteristics. These are similar to ones that appear in Josephson junctions. A knowledge of the properties of Shapiro steps would provide important information on the properties of fluxons. An exact, nonperturbative calculation of the sizes of Shapiro steps is given for a periodic field having the form of a symmetric pulse. C1 NIH,BETHESDA,MD 20892. RP SHAPIRO, BY (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52900 RAMAT GAN,ISRAEL. NR 15 TC 12 Z9 12 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0163-1829 J9 PHYS REV B JI Phys. Rev. B PD OCT 1 PY 1992 VL 46 IS 13 BP 8416 EP 8420 DI 10.1103/PhysRevB.46.8416 PG 5 WC Physics, Condensed Matter SC Physics GA JT040 UT WOS:A1992JT04000054 ER PT J AU COLOMBO, G HANSEN, C HOFFMAN, PL GRANT, KA AF COLOMBO, G HANSEN, C HOFFMAN, PL GRANT, KA TI DECREASED PERFORMANCE IN A DELAYED ALTERNATION TASK BY RATS GENETICALLY DEFICIENT IN VASOPRESSIN SO PHYSIOLOGY & BEHAVIOR LA English DT Note DE VASOPRESSIN; VASOPRESSIN-DEFICIENT RATS; M520 STRAIN; T-MAZE; DELAYED ALTERNATION; FOOD-REINFORCEMENT; ACQUISITION; MEMORY ID PASSIVE-AVOIDANCE BEHAVIOR; DIABETES-INSIPIDUS; MEMORY; MICROINJECTION; HIPPOCAMPUS; INJECTIONS; PREVENTS; SERUM AB Acquisition and retention of a delayed alternation task by rats genetically deficient in vasopressin (AVP) due to the homozygous occurrence of the Brattleboro diabetes insipidus (DI) gene (M520/DI) were compared to the response of rats that were heterozygous (M520/HZ) or normal (M520/N) with respect to the DI gene. No significant difference in the adaptation to the apparatus was observed between the groups. However, the rate at which the M520/DI rats acquired the alternation task was significantly slower than the acquisition rates of M520/HZ and M520/N rats. In addition, the maximum intertrial interval reached by the M520/DI rats was significantly shorter than the intertrial intervals reached by the M520/HZ and M520/N rats, indicating the ability to retain information was impaired in the M520/DI rats. These results are consistent with the hypothesis that AVP modulates the acquisition and retention of information for normal memory processes. C1 NIH,DIV RES SERV,VET RESOURCES BRANCH,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. NIAAA,DIV INTRAMURAL CLIN & BIOMED RES,BETHESDA,MD 20892. NR 23 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD OCT PY 1992 VL 52 IS 4 BP 827 EP 830 DI 10.1016/0031-9384(92)90422-X PG 4 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA JT020 UT WOS:A1992JT02000035 PM 1409961 ER PT J AU CHARLTON, TS MARINI, AM MARKEY, SP NORSTOG, K DUNCAN, MW AF CHARLTON, TS MARINI, AM MARKEY, SP NORSTOG, K DUNCAN, MW TI QUANTIFICATION OF THE NEUROTOXIN 2-AMINO-3-(METHYLAMINO)-PROPANOIC ACID (BMAA) IN CYCADALES SO PHYTOCHEMISTRY LA English DT Article DE CYCADALES; CYCADS; QUANTITATIVE GC-MS; 2-AMINO-3-(METHYLAMINO)PROPANOIC ACID (BMAA); BETA-METHYLDIAMINOPROPANOIC ACID; ALS-PD; GUAM ID LATERAL SCLEROSIS PARKINSONISM AB Cycads have been recognized as toxic for many years and are known to cause hind limb ataxia in grazing animals. The L-isomer of 2-amino-3-(methylamino)propanoic acid (BMAA; beta-methyldiaminopropanonic acid), a constituent of cycads, has recently been implicated in the onset of human neurologic disorders. We have used combined gas chromatography-mass spectrometry (GC-MS) to determine the BMAA content of the leaves (n = 30) and female gametophyte (n = 11) of a variety of cycads. A stable isotopomer of BMAA (i.e. [H-2(3)] BMAA) was used as an internal standard to optimize specificity and precision. BMAA content is greater in members of the genus Cycas (i.e. up to 1800 mug g-1 fr. wt) whereas smaller amounts (i.e. < 40 mug g-1) are present in members of the six other genera tested. Where BMAA content of both leaves and seeds was determined in the same species (n = 4), values were comparable. Based on our results we estimate that grazing animals are exposed to exceedingly low doses of BMAA. These data would tend to exclude BMAA as the etiologic agent in hind limb ataxia in grazing animals. C1 FAIRCHILD TROP GARDEN,MIAMI,FL 33156. NIMH,ANALYT CHEM SECT,BETHESDA,MD 20892. NINCDS,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. RP CHARLTON, TS (reprint author), UNIV NEW S WALES,BIOMED MASS SPECTROMETRY UNIT,POB 1,KENSINGTON,NSW 2033,AUSTRALIA. NR 17 TC 17 Z9 17 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD OCT PY 1992 VL 31 IS 10 BP 3429 EP 3432 DI 10.1016/0031-9422(92)83700-9 PG 4 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA JT410 UT WOS:A1992JT41000024 ER PT J AU SIMPSON, JL MILLS, JL RHOADS, GG CUNNINGHAM, G AF SIMPSON, JL MILLS, JL RHOADS, GG CUNNINGHAM, G TI FOLIC-ACID AND NEURAL-TUBE DEFECT AVOIDANCE - REPLY SO PRENATAL DIAGNOSIS LA English DT Letter ID PREGNANCY; VITAMINS C1 NICHHD,BETHESDA,MD 20892. ROBERT WOOD JOHNSON MED SCH,PISCATAWAY,NJ 08854. CALIF PUBL HLTH FDN,BERKELEY,CA 94704. RP SIMPSON, JL (reprint author), UNIV TENNESSEE,MEMPHIS,TN 38103, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD OCT PY 1992 VL 12 IS 10 BP 858 EP 859 DI 10.1002/pd.1970121019 PG 2 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA JV667 UT WOS:A1992JV66700017 ER PT J AU PINTO, A ALDINUCCI, D GATTEI, V ZAGONEL, V TORTORA, G BUDILLON, A CHOCHUNG, YS AF PINTO, A ALDINUCCI, D GATTEI, V ZAGONEL, V TORTORA, G BUDILLON, A CHOCHUNG, YS TI INHIBITION OF THE SELF-RENEWAL CAPACITY OF BLAST PROGENITORS FROM ACUTE MYELOBLASTIC-LEUKEMIA PATIENTS BY SITE-SELECTIVE 8-CHLOROADENOSINE 3',5'-CYCLIC-MONOPHOSPHATE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SITE-SELECTIVE CAMP ANALOGS; LEUKEMIC STEM CELLS; CLONOGENIC GROWTH; CELL DIFFERENTIATION ID ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; PROTEIN-KINASE ISOZYMES; CAMP ANALOGS; CYTOSINE-ARABINOSIDE; GROWTH-FACTORS; BINDING-SITES; FACTOR-ALPHA; CELLS; DIFFERENTIATION AB The physiologic balance between the two regulatory subunit isoforms, RI and RII, of cAMP-dependent protein kinase is disrupted in cancer cells; growth arrest and differentiation of malignant cells can be achieved when the normal ratio of these intracellular signal transducers of cAMP is restored by the use of site-selective cAMP analogs. In this study we evaluated the effects of the site-selective cAMP analog 8-chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cAMP) on clonogenic growth of blast progenitors from 15 patients with acute myeloblastic leukemia and 3 patients affected by advanced myelodysplastic syndrome. Leukemic blast progenitors undergo terminal divisions, giving rise to colonies in methylcellulose. The self-renewal capacity of blast progenitors is conversely reflected in a secondary methylcellulose assay after exponential growth of clonogenic cells in suspension cultures. In all the samples tested, 8-Cl-cAMP, at micromolar concentrations (0.1-50 muM), suppressed in a dose-dependent manner both primary colony formation in methylcellulose and the recovery of clonogenic cells from suspension culture. Strikingly, in the samples from the entire group of patients, 8-Cl-cAMP was more effective in inhibiting the self-renewing clonogenic cells than the terminally dividing blast cells (P = 0.005). In addition, in four out of six cases studied, 8-Cl-cAMP was able to induce a morphologic and/or immunophenotypic maturation of leukemic blasts. An evident reduction of RI levels in fresh leukemic cells after exposure to 8-Cl-cAMP was also detected. Our results showing that 8-Cl-cAMP is a powerful inhibitor of clonogenic growth of leukemic blast progenitors by primarily suppressing their self-renewal capacity indicate that this site-selective cAMP analog represents a promising biological agent for acute myeloblastic leukemia therapy in humans. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 5B38,BETHESDA,MD 20892. NAPLES UNIV,CATTEDRA ONCOL MED,I-80138 NAPLES,ITALY. IST NAZL RIC & CURA CARATTERE SCI,LEUKEMIA UNIT,I-33081 AVIANO,ITALY. IST NAZL RIC & CURA CARATTERE SCI,CTR REFERIMENTO ONCO,DIV EXPTL ONCOL,I-33081 AVIANO,ITALY. IST NAZL RIC & CURA CARATTERE SCI,CTR RIFERIMENTO ONCOL,DIV MED ONCOL,I-33081 AVIANO,ITALY. RI zagonel, vittorina/F-4226-2014; OI zagonel, vittorina/0000-0002-0829-2525; Budillon, Alfredo/0000-0002-6330-6053 NR 34 TC 27 Z9 28 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 OCT 1 PY 1992 VL 89 IS 19 BP 8884 EP 8888 DI 10.1073/pnas.89.19.8884 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400006 PM 1329084 ER PT J AU BOYKO, VP KARASEV, AV AGRANOVSKY, AA KOONIN, EV DOLJA, VV AF BOYKO, VP KARASEV, AV AGRANOVSKY, AA KOONIN, EV DOLJA, VV TI COAT PROTEIN GENE DUPLICATION IN A FILAMENTOUS RNA VIRUS OF PLANTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BEET YELLOWS CLOSTEROVIRUS; NUCLEOTIDE-SEQUENCE; TRANSLATION; EVOLUTION; ACID AB Computer-assisted analysis revealed a striking sequence similarity between the putative 24-kDa protein (p24) encoded by open reading frame (ORF) 5 of beet yellows closterovirus and the coat protein of this virus encoded by the adjacent ORF6. Both of these proteins are closely related to the homologous proteins of another closterovirus, citrus tristeza virus. It is hypothesized that the genes for coat protein and its diverged tandem copy have evolved by duplication. Phylogenetic analysis using various methods for tree generation suggested that the duplication was already present in the genome of the common ancestor of the two closteroviruses. The genes for p24 and coat protein of beet yellows closterovirus were cloned, transcribed, and translated in vitro yielding products of the expected size. It was shown that p24 is translated starting from the first of the two alternative AUG codons located near the 5' terminus of ORF5. The presence of a single protein species in beet yellows closterovirus virions and the near identity of the amino acid composition of this protein with the composition of the ORF6 but not the ORF5 product indicated that p24 is not a major virion component. Most of the amino acids that are conserved in the coat proteins of filamentous viruses of plants are retained also in p24. These observations suggest that p24 may share some structural and functional features with the coat protein but probably fulfills a distinct function in virus reproduction. C1 MV LOMONOSOV STATE UNIV,AN BELOZERSKY LAB,MOSCOW 119899,USSR. RUSSIAN ACAD SCI,INST MICROBIOL,MOSCOW 117811,USSR. NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NR 40 TC 55 Z9 57 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 OCT 1 PY 1992 VL 89 IS 19 BP 9156 EP 9160 DI 10.1073/pnas.89.19.9156 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400062 PM 1409617 ER PT J AU LIN, D SHIELDS, MT ULLRICH, SJ APPELLA, E MERCER, WE AF LIN, D SHIELDS, MT ULLRICH, SJ APPELLA, E MERCER, WE TI GROWTH ARREST INDUCED BY WILD-TYPE P53 PROTEIN BLOCKS CELLS PRIOR TO OR NEAR THE RESTRICTION POINT IN LATE G1 PHASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CELL CYCLE; GENE EXPRESSION; B-MYB GENE ID PERIPHERAL-BLOOD LYMPHOCYTES; SELECTIVE DOWN-REGULATION; C-MYB; MESSENGER-RNA; THYMIDINE KINASE; GENE-PRODUCT; B-MYB; CYCLE; EXPRESSION; ONCOGENE AB Conditional expression of wild-type (wt) p53 protein in a glioblastoma tumor cell tine has been shown to be growth inhibitory. We have now more precisely localized the position in the cell cycle where growth arrest occurs. We show that growth arrest occurs prior to or near the restriction point in late G, phase of the cell cycle. The effect of wt p53 protein on the expression of four immediate-early genes (c-FOS, c-JUN, JUN-B, and c-MYC), one delayed-early gene (ornithine decarboxylase), and two late-G1/S-phase genes (B-MYB and DNA polymerase alpha) was also examined. Of this subset of growth response genes, only the expression of B-MYB and DNA polymerase alpha was significantly repressed. The possibility that decreased expression of B-MYB may be an important component of growth arrest mediated by wt p53 protein is discussed. C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. NCI,CELL BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA 09644, CA 42866]; NCRR NIH HHS [SO7 RR0 5417] NR 43 TC 307 Z9 309 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 OCT 1 PY 1992 VL 89 IS 19 BP 9210 EP 9214 DI 10.1073/pnas.89.19.9210 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400073 PM 1409626 ER PT J AU TSAI, SC ADAMIK, R HAUN, RS MOSS, J VAUGHAN, M AF TSAI, SC ADAMIK, R HAUN, RS MOSS, J VAUGHAN, M TI DIFFERENTIAL INTERACTION OF ADP-RIBOSYLATION FACTOR-I, FACTOR-III, AND FACTOR-5 WITH RAT-BRAIN GOLGI MEMBRANES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHOLERA TOXIN; PROTEIN TRAFFICKING; ENDOPLASMIC RETICULUM; VESICULAR TRANSPORT ID GTP-BINDING PROTEINS; CHOLERA-TOXIN; ADENYLATE-CYCLASE; NUCLEOTIDE; EXPRESSION; TRANSPORT; VESICLES; ACTIVATORS; COFACTOR; COMPLEX AB Six mammalian ADP-ribosylation factors (ARFs) identified by cDNA cloning were expressed as recombinant proteins (rARFs) that stimulated cholera toxin ADP-ribosyltransferase activity. Microsequencing of soluble ARFs I and II (sARFs I and II), purified from bovine brain, established that they are ARFs 1 and 3, respectively. Rabbit antibodies (IgG) against sARF II reacted similarly with ARFs 1, 2, and 3 (class I) on Western blots. ARFs 1 and 3 were distinguished by their electrophoretic mobilities. Antiserum against rARF 5 cross-reacted partially with rARF 4 but not detectably with rARF 6 and minimally with class I ARFs. Guanosine 5'-O-(3-thiotriphosphate) (GTP[gammaS]) increased recovery of ARF activity and immunoreactivity in organelle fractions separated by density gradient centrifugation, after incubation of rat brain homogenate with ATP and a regenerating system. ARF 1 accumulated in microsomes plus Golgi and Golgi fractions, whereas ARF 5 seemed to localize more specifically in Golgi; the smaller increment in ARF 3 was distributed more evenly among fractions. On incubation of Golgi with a crude ARF fraction, GTP[gammaS], and an ATP-regenerating system, association of ARF activity with Golgi increased with increasing ATP concentration paralleled by increases in immunoreactive ARFs 1 and 5 and, to a lesser degree, ARF 3. Golgi incubated with GTP[gammaS] and purified ARF 1 or 3 bound more ARF 1 than ARF 3. Based on immunoreactivity and assay of ARF activity, individual ARFs 1, 3, and 5 appeared to behave independently and selectively in their GTP-dependent association with Golgi in vitro. RP TSAI, SC (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. NR 33 TC 51 Z9 52 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 1 PY 1992 VL 89 IS 19 BP 9272 EP 9276 DI 10.1073/pnas.89.19.9272 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400086 PM 1409634 ER PT J AU ASHIZAWA, K CHENG, SY AF ASHIZAWA, K CHENG, SY TI REGULATION OF THYROID-HORMONE RECEPTOR-MEDIATED TRANSCRIPTION BY A CYTOSOL PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-HORMONE; TRANSPORT; BINDING; CELLS; FRUCTOSE-1,6-BISPHOSPHATE; EXPRESSION; PLASMA; CDNA AB Thyroid hormone receptors (TRs) are members of the steroid hormone/retinoic acid receptor superfamily, which regulate homeostasis, development, and differentiation. Their transcriptional activity is modulated by the thyroid hormone 3,3',5-triiodo-L-thyronine (T3). The present study evaluated the effect of the availability of cytoplasmic T3 on the modulation of transcriptional responses of the TRs. In human choriocarcinoma JEG-3 and monkey COS-1 cells, the cytosolic thyroid hormone binding protein is a monomer of the tetrameric pyruvate kinase, subtype M2, which does not bind T3. The in vivo monomer-tetramer interconversion is regulated by glucose via fructose 1,6-bisphosphate. At the physiological T3 concentration, lowering the glucose concentration led to an increase in the cellular concentration of the cytosolic thyroid hormone binding protein. By using a transient transfection system, a concomitant reduction in the transcriptional activity of the human beta1 thyroid hormone receptor was detected in both cell lines. In the absence of glucose, the transcriptional activity of the human beta1 thyroid hormone receptor in JEG-3 and COS-1 cells was reduced by 65-75% and 90-95%, respectively. However, glucose had no effect on the basal transcriptional activity. These findings demonstrate an important prenuclear step in the modulation of the gene regulating activity of the TRs. C1 NCI,DIV CANC BIOL & DIAG,MOLEC BIOL LAB,GENE REGULAT SECT,900 ROCKVILLE PIKE,BLDG 37,ROOM 4B09,BETHESDA,MD 20892. NR 28 TC 44 Z9 46 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 OCT 1 PY 1992 VL 89 IS 19 BP 9277 EP 9281 DI 10.1073/pnas.89.19.9277 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400087 PM 1409635 ER PT J AU KELLEY, MJ PECH, M SEUANEZ, HN RUBIN, JS OBRIEN, SJ AARONSON, SA AF KELLEY, MJ PECH, M SEUANEZ, HN RUBIN, JS OBRIEN, SJ AARONSON, SA TI EMERGENCE OF THE KERATINOCYTE GROWTH-FACTOR MULTIGENE FAMILY DURING THE GREAT APE RADIATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FIBROBLAST GROWTH FACTORS; GENE AMPLIFICATION; PRIMATE EVOLUTION ID FACTOR GENE FAMILY; GEL-ELECTROPHORESIS; ORGANIZATION; SEQUENCE; DNA; HST; AMPLIFICATION; FGF; EUKARYOTES; DISPERSION AB The structural gene for human keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, consists of three coding exons and two introns typical of other fibroblast growth factor loci. A portion of the KGF gene, located on chromosome 15, is amplified to almost-equal-to 16 copies in the human genome, and these highly related copies (which consist of exon 2, exon 3, the intron between them, and a 3' noncoding segment of the KGF transcript) are dispersed to multiple human chromosomes. The KGF-like sequences are transcriptionally active, differentially regulated in various tissues, and composed of three distinct classes of coding sequences that are 5% divergent from each other and from the authentic KGF sequence. Multiple copies of KGF-like genes were also discovered in the genomic DNAs of chimpanzee and gorilla but were not found in lesser apes (gibbon), Old World monkeys (African green monkey and macaques), mice, or chickens. The pattern of evolutionary occurrence suggests that a primordial KGF gene was amplified and chromosomally dispersed subsequent to the divergence of orangutan from African apes but before the trichotomous divergence of human, chimpanzee, and gorilla 5-8 million years ago. The appearance of a transcriptionally active and chromosomally dispersed multigene KGF family may have implications in the evolution of the great apes and humans. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. F HOFFMANN LA ROCHE & CO LTD,PHARMA DIV,PRECLIN RES,CH-4002 BASEL,SWITZERLAND. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. OI Kelley, Michael/0000-0001-9523-6080 NR 38 TC 31 Z9 32 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 OCT 1 PY 1992 VL 89 IS 19 BP 9287 EP 9291 DI 10.1073/pnas.89.19.9287 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400089 PM 1409637 ER PT J AU KIM, RY GASSER, R WISTOW, GJ AF KIM, RY GASSER, R WISTOW, GJ TI MU-CRYSTALLIN IS A MAMMALIAN HOMOLOG OF AGROBACTERIUM-ORNITHINE CYCLODEAMINASE AND IS EXPRESSED IN HUMAN RETINA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CRYSTALLIN RECRUITMENT; MOLECULAR EVOLUTION; AMINO ACID METABOLISM ID TI PLASMID C58; LENS CRYSTALLINS; STRUCTURAL PROTEIN; ENZYME PROPERTIES; DNA-SEQUENCE; GENE; EVOLUTION; DEHYDROGENASE; RECRUITMENT; PROLINE AB Mu-crystallin is the major component of the eye lens in several Australian marsupials. The complete sequence of kangaroo mu-crystallin has now been obtained by cDNA cloning. The predicted amino acid sequence shows similarity with ornithine cyclodeaminases encoded by the tumor-inducing (Ti) plasmids of Agrobacterium tumefaciens. Until now, neither ornithine cyclodeaminase nor any structurally related enzymes have been observed in eukaryotes. RNA analysis of kangaroo tissues shows that mu-crystallin is expressed at high abundance in lens, but outside the lens mu-crystallin is preferentially expressed in neural tissues, retina, and brain. An almost full-length cDNA for mu-crystallin was cloned from human retina. In human tissues, mu-crystallin mRNA is present in neural tissue, muscle, and kidney. This pattern of expression and relationship to an enzyme involved in unusual amino acid metabolism suggests the interesting possibility that mammalian mu-crystallins could be enzymes participating in processes such as osmoregulation or the metabolism of excitatory amino acids. C1 NEI,MOLEC & DEV BIOL LAB,MOLEC STRUCT & FUNCT SECT,ROOM 222,BLDG 6,BETHESDA,MD 20892. UNIV MELBOURNE,SCH VET SCI,WERRIBEE,VIC 3030,AUSTRALIA. NR 24 TC 65 Z9 68 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 OCT 1 PY 1992 VL 89 IS 19 BP 9292 EP 9296 DI 10.1073/pnas.89.19.9292 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400090 PM 1384048 ER PT J AU BARBAS, CF BJORLING, E CHIODI, F DUNLOP, N CABABA, D JONES, TM ZEBEDEE, SL PERSSON, MAA NARA, PL NORRBY, E BURTON, DR AF BARBAS, CF BJORLING, E CHIODI, F DUNLOP, N CABABA, D JONES, TM ZEBEDEE, SL PERSSON, MAA NARA, PL NORRBY, E BURTON, DR TI RECOMBINANT HUMAN FAB FRAGMENTS NEUTRALIZE HUMAN TYPE-1 IMMUNODEFICIENCY VIRUS INVITRO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIBODY REPERTOIRE; PASSIVE IMMUNIZATION; VIRUS NEUTRALIZATION; PHAGE SURFACE EXPRESSION ID HUMAN MONOCLONAL-ANTIBODY; CD4 RECEPTOR; HIV-1 GP120; LIBRARIES; BINDING; INFECTION; GENERATION; EPITOPE; SITE AB A panel of 20 recombinant Fab fragments reactive with the surface glycoprotein gp120 of human type 1 immunodeficiency virus (HIV-1) were examined for their ability to neutralize MN and IIIB strains of the virus. Neutralization was determined as the ability of the Fab fragments to inhibit infection as measured in both a p24 ELISA and a syncytium-formation assay. One group of closely sequence-related Fab fragments was found to neutralize virus in both assays with a 50% neutralization titer at almost-equal-to 1 mug/ml. Another Fab neutralized in the p24 ELISA but not in the syncytium assay. The other Fab fragments showed weak or no neutralizing ability. The results imply that virion aggregation or crosslinking of gp120 molecules on the virion surface is not an absolute requirement for HIV-1 neutralization. Further, all of the Fab fragments were shown to be competitive with soluble CD4 for binding to gp120 and yet few neutralized the virus effectively, implying that the mechanism of neutralization in this case may not involve receptor blocking. The observation of a preponderance of high-affinity Fab fragments with poor or no neutralizing ability could have implications for vaccine strategies. C1 SCRIPPS RES INST, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. RW JOHNSON PHARMACEUT RES INST, SAN DIEGO, CA 92121 USA. NCI, FREDERICK CANC RES & DEV CTR, VIRUS BIOL SECT, TUMOR CELL BIOL LAB, FREDERICK, MD 21701 USA. KAROLINSKA INST, DEPT MED, S-10401 STOCKHOLM 60, SWEDEN. KAROLINSKA INST, DEPT VIROL, S-10521 STOCKHOLM, SWEDEN. RP BARBAS, CF (reprint author), SCRIPPS RES INST, DEPT MOLEC BIOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. NR 38 TC 233 Z9 236 U1 1 U2 6 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 1 PY 1992 VL 89 IS 19 BP 9339 EP 9343 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400100 PM 1384050 ER PT J AU DURAND, GM GREGOR, P ZHENG, X BENNETT, MVL UHL, GR ZUKIN, RS AF DURAND, GM GREGOR, P ZHENG, X BENNETT, MVL UHL, GR ZUKIN, RS TI CLONING OF AN APPARENT SPLICE VARIANT OF THE RAT N-METHYL-D-ASPARTATE RECEPTOR NMDAR1 WITH ALTERED SENSITIVITY TO POLYAMINES AND ACTIVATORS OF PROTEIN-KINASE-C SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE EXCITATORY AMINO ACID RECEPTORS; GLUTAMATE RECEPTORS; XENOPUS OOCYTE EXPRESSION; PHORBOL ESTERS ID FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; XENOPUS OOCYTES; NERVOUS-SYSTEM; GLUTAMATE; SUBUNIT; FAMILY; AMPA; RESPONSES; CHANNELS AB Molecular cloning identified complementary DNA species, from a rat ventral midbrain library, encoding apparent splice variants of the N-methyl-D-aspartate (NMDA) receptor NMDAR1 (which we now term NR1a). Sequencing revealed that one variant, NR1b, differs from NR1a by the presence of a 21-amino acid insert near the amino end of the N-terminal domain and by an alternate C-terminal domain in which the last 75 amino acids are replaced by an unrelated sequence of 22 amino acids. NR1b is virtually identical to NR1a n the remainder of the N- and C-terminal domains, at the 5' and 3' noncoding ends, and within the predicted transmembrane domains and extracellular and cytoplasmic loops. These findings suggest that the two forms of the receptor arise by differential spiking of a transcript from the same gene. Sequencing of other clones indicates the existence of a third variant, NR1c, identical to NR1b in its C terminus but lacking the N-terminal insert. NR1b RNA injected into Xenopus oocytes generated functional homomeric NMDA channels with electrophysiological properties distinct from those of NR1a homomeric channels. NR1b channels exhibited a lower apparent affinity for NMDA and for glutamate. NR1b channels exhibited a lower affinity for D-2-amino-5-phosphonovaleric acid and a higher affinity for Zn2+. The two receptor variants showed nearly identical affinities for glycine, Mg2+, and phencyclidine. Spermine potentiation of NMDA responses, prominent in oocytes injected with rat forebrain message, was also prominent for NR1a receptors, but was greatly reduced or absent for NR1b receptors. Treatment with the protein kinase C activator phorbol 12-myristate 13-acetate potentiated NMDA responses in NR1b-injected oocytes by about 20-fold; potentiation of NMDA responses in NR1a-injected oocytes was much less, about 4-fold. These findings support a role for alternate splicing in generating NMDA channels with different functional properties. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,MOLEC NEUROBIOL LAB,LEXINGTON,KY 40583. FU NICHD NIH HHS [HD 04248]; NINDS NIH HHS [NS 20752, NS 07412] NR 29 TC 269 Z9 272 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 OCT 1 PY 1992 VL 89 IS 19 BP 9359 EP 9363 DI 10.1073/pnas.89.19.9359 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JQ934 UT WOS:A1992JQ93400104 PM 1409641 ER PT J AU SANSOM, CE WU, J WEBER, IT AF SANSOM, CE WU, J WEBER, IT TI MOLECULAR MECHANICS ANALYSIS OF INHIBITOR BINDING TO HIV-1 PROTEASE SO PROTEIN ENGINEERING LA English DT Article DE ASPARTIC PROTEASES; HIV-1; INHIBITOR BINDING; MOLECULAR MECHANICS ID HUMAN IMMUNODEFICIENCY VIRUS-1; RETROVIRAL PROTEASE; POL POLYPROTEINS; ASPARTIC PROTEASES; CRYSTAL-STRUCTURE; TYPE-1 PROTEASE; ACTIVE-SITE; RESOLUTION; SPECIFICITY; PROTEINASE AB Crystallographic structures of HIV protease with three different peptide-mimetic inhibitors were subjected to energy minimization using molecular mechanics, the minimized structures analyzed and the inhibitor binding energies calculated. Partial charge assignment for the hydrogen bonded catalytic aspartic acids, Asp25 and -25', was in good agreement with charge calculations using semi-empirical molecular orbital methods. Root mean square deviations on minimization were small and similar for both subunits in the protease dimer. The surface loops, which had the largest B factors, changed most on minimization; the hydrophobic core and the inhibitor binding site showed little change. The distance-dependent dielectric of D(r) = 4r was found to be preferable to D(r) = r. Distance restraints were applied for the intermolecular hydrogen bonds to maintain the conformation of the inhibitor binding site. Using the dielectric of D(r) = 4r, the calculated interaction energy of the three inhibitors with the protease ranged from -53 to -56 kcal/mol. The psi groups of the inhibitors were changed to add or remove a 'transition state analogue' hydroxyl group, and the loss in energy on the removal of this group was calculated to be 0.9-1.7 kcal/mol. This would represent 19-36% of the total measured difference in binding energy between the inhibitors JG365 and MVT-101. C1 THOMAS JEFFERSON UNIV, JEFFERSON CANC INST, PHILADELPHIA, PA 19107 USA. NCI, FREDERICK CANC RES FACIL, MACROMOLEC STRUCT LAB, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101] NR 44 TC 31 Z9 31 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD OCT PY 1992 VL 5 IS 7 BP 659 EP 667 DI 10.1093/protein/5.7.659 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA JY143 UT WOS:A1992JY14300009 PM 1480620 ER PT J AU BURNETTE, B KAHN, R GLOVER, CJ FELSTED, RL AF BURNETTE, B KAHN, R GLOVER, CJ FELSTED, RL TI BACTERIAL EXPRESSION, PURIFICATION, AND INVITRO N-MYRISTOYLATION OF HIV-1 P17(GAG) SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; MURINE LEUKEMIA-VIRUS; MATRIX PROTEIN; GAG PRECURSOR; SACCHAROMYCES-CEREVISIAE; RNA-POLYMERASE; D RETROVIRUSES; MYRISTYLATION; IDENTIFICATION; POLYPROTEIN RP BURNETTE, B (reprint author), NCI,DIV CANCER TREATMENT,BIOL CHEM LAB,BLDG 37,ROOM 5D02,BETHESDA,MD 20894, USA. NR 37 TC 7 Z9 8 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD OCT PY 1992 VL 3 IS 5 BP 395 EP 402 DI 10.1016/S1046-5928(05)80041-5 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA JT408 UT WOS:A1992JT40800007 PM 1458053 ER PT J AU CHEN, X YANG, YS ZHENG, YQ MARTIN, BM DUFFEL, MW JAKOBY, WB AF CHEN, X YANG, YS ZHENG, YQ MARTIN, BM DUFFEL, MW JAKOBY, WB TI TYROSINE-ESTER SULFOTRANSFERASE FROM RAT-LIVER - BACTERIAL EXPRESSION AND IDENTIFICATION SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID ARYL SULFOTRANSFERASE; PROTEINS; IV; SEQUENCE; ASSAY C1 UNIV IOWA,COLL PHARM,DIV MED & NAT PROD CHEM,IOWA CITY,IA 52242. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892. RP CHEN, X (reprint author), NIDDKD,BIOCHEM & METAB LAB,BLDG 10,ROOM 9N119,BETHESDA,MD 20892, USA. RI Duffel, Michael/E-6066-2015 OI Duffel, Michael/0000-0002-6079-7459 FU NCI NIH HHS [CA38683, R01 CA038683] NR 24 TC 39 Z9 42 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD OCT PY 1992 VL 3 IS 5 BP 421 EP 426 DI 10.1016/S1046-5928(05)80045-2 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA JT408 UT WOS:A1992JT40800011 PM 1458056 ER PT J AU LAUER, CJ KRIEG, JC GARCIABORREGUERO, D OZDAGLAR, A HOLSBOER, F AF LAUER, CJ KRIEG, JC GARCIABORREGUERO, D OZDAGLAR, A HOLSBOER, F TI PANIC DISORDER AND MAJOR DEPRESSION - A COMPARATIVE ELECTROENCEPHALOGRAPHIC SLEEP STUDY SO PSYCHIATRY RESEARCH LA English DT Article DE AFFECTIVE DISORDER; ANXIETY; POLYSOMNOGRAPHY; RAPID EYE MOVEMENT LATENCY; AGORAPHOBIA ID GENERALIZED ANXIETY DISORDER; INDUCTION TEST; REM-SLEEP; AGORAPHOBIA; DEPRIVATION; ATTACKS; HYPOTHESIS; SEPARATION; MECHANISMS; FAMILY AB Family studies suggest some common etiological factors in panic disorder and depression. The observation of characteristic depression-like polysomnographic alterations in panic disorder patients would further underline the assumed biological interface between the two psychiatric disorders. In a polysomnographic study of 22 inpatients with panic disorder, 12 inpatients with major depression, and 12 control subjects, we found that both groups of patients had one major feature of depression-like sleep: a shortened rapid eye movement (REM) latency. However, the patterns of the first hours of polysomnography showed more differences than similarities between these psychiatric disorders, indicating that the shortened REM latency apparently is merely a common final pathway of different alterations in sleep regulation. Our findings, therefore, provide more evidence against than for a significant biological interface between panic disorder and depression. C1 NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. PSYCHIAT HOSP,EMMENDINGEN,GERMANY. RP LAUER, CJ (reprint author), MAX PLANCK INST PSYCHIAT,INST CLIN,KRAEPELINSTR 10,W-8000 MUNICH 40,GERMANY. NR 51 TC 26 Z9 27 U1 2 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD OCT PY 1992 VL 44 IS 1 BP 41 EP 54 DI 10.1016/0165-1781(92)90068-E PG 14 WC Psychiatry SC Psychiatry GA KB532 UT WOS:A1992KB53200005 PM 1461946 ER PT J AU CASANOVA, MF ZITO, M ALTSHULER, L WEINBERGER, DR KLEINMAN, JE AF CASANOVA, MF ZITO, M ALTSHULER, L WEINBERGER, DR KLEINMAN, JE TI NORMAL NUCLEOLAR SIZE OF ENTORHINAL CORTEX CELLS IN SCHIZOPHRENIA SO PSYCHIATRY RESEARCH LA English DT Letter ID RHESUS-MONKEY; HIPPOCAMPAL-FORMATION; PARAHIPPOCAMPAL GYRUS; SENILE DEMENTIA; CONNECTIONS; PATHOLOGY; AREA; EFFERENTS; AMYGDALA; CORTICES C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. RP CASANOVA, MF (reprint author), MED COLL GEORGIA,DEPT PSYCHIAT & HLTH BEHAV,AUGUSTA,GA 30912, USA. NR 24 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD OCT PY 1992 VL 44 IS 1 BP 79 EP 82 DI 10.1016/0165-1781(92)90072-B PG 4 WC Psychiatry SC Psychiatry GA KB532 UT WOS:A1992KB53200009 PM 1461950 ER PT J AU KATZ, JL WITKIN, JM AF KATZ, JL WITKIN, JM TI SELECTIVE EFFECTS OF THE D1 DOPAMINE RECEPTOR AGONIST, SKF-38393, ON BEHAVIOR MAINTAINED BY COCAINE INJECTION IN SQUIRREL-MONKEYS SO PSYCHOPHARMACOLOGY LA English DT Note DE COCAINE; SELF ADMINISTRATION; D1 DOPAMINE AGONISTS; SKF-38393; REINFORCEMENT; SQUIRREL MONKEYS ID DISCRIMINATIVE STIMULUS PROPERTIES; RHESUS-MONKEYS; INVOLVEMENT; ANTAGONIST; SUBTYPES; RAT AB The effects of the dopamine receptor D1 partial agonist, SKF 38393, on behavior maintained by cocaine was assessed in squirrel monkeys (Saimiri sciureus). One group of subjects was trained to press a key under a fixed-group 30-response schedule of cocaine injection; when green stimulus lamps were illuminated each 30th response produced an injection (17 mug/kg) followed by a 1-min period during which the lights were out and responses had no scheduled consequences. Another group of squirrel monkeys was trained under an identical schedule with food reinforcement. SKF 38393 produced dose-related decreases in rates of responding maintained by either cocaine injection or food presentation. Rates of responding maintained by cocaine were decreased to a greater extent than those maintained by food. The-ED50 value for SKF 38393 for responding maintained by cocaine was 2.53 mg/kg (95% CL: 1.22-5.23), whereas that value was 15.63 mg/kg (95% CL: 2.83-86.33) for responding maintained by food. Rates of responding maintained by cocaine were an inverted-U-shaped function of dose. Pretreatment treatment with 3.0 mg/kg SKF 38393 shifted the ascending limb of the cocaine dose-effect curve to the right. These findings suggest that indirect D1-receptor activation plays a role in the reinforcing effects of cocaine, and that drugs acting at D1 receptors may show promise as therapeutic agents in the treatment of cocaine abuse. RP KATZ, JL (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,PSYCHOBIOL LAB,POB 5180,BALTIMORE,MD 21224, USA. OI Katz, Jonathan/0000-0002-1068-1159 NR 19 TC 46 Z9 47 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 OCT PY 1992 VL 109 IS 1-2 BP 241 EP 244 DI 10.1007/BF02245508 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA JQ592 UT WOS:A1992JQ59200034 PM 1365665 ER PT J AU LI, R WING, LL KIRCH, DG WYATT, RJ CHUANG, DM AF LI, R WING, LL KIRCH, DG WYATT, RJ CHUANG, DM TI EFFECTS OF CHRONIC NICOTINE AND HALOPERIDOL ADMINISTRATION ON MUSCARINIC RECEPTOR-MEDIATED PHOSPHOINOSITIDE TURNOVER IN RAT-BRAIN SLICES SO PSYCHOPHARMACOLOGY LA English DT Note DE NICOTINE; HALOPERIDOL; PHOSPHOINOSITIDE TURNOVER; MUSCARINIC RECEPTOR ID TARDIVE-DYSKINESIA; SMOKING; SYSTEM AB Muscarinic receptor-mediated phosphoinositide (PI) turnover in rat brain slices was assessed after chronic administration of nicotine (12 mg/kg/day) or haloperidol decanoate (1.5 mg/kg/day), either alone or in combination, for 6 weeks. Nicotine alone did not significantly alter carbachol-induced inositol monophosphate (IP1) accumulation in the frontal cortex, but did result in a significant increase in the hippocampus, and in a decrease in the striatum. Haloperidol alone attenuated carbachol-stimulated IP1 accumulation in all three brain regions. Chronic treatment with combined nicotine and haloperidol resulted in no significant change in carbachol-sensitive IP1 accumulation in either the frontal cortex or hippocampus but did result in a decrease in the striatum. The results suggest significant cross-talk between cholinergic and dopaminergic systems in affecting PI metabolism. C1 NIMH, DIV CLIN RES, ROCKVILLE, MD 20857 USA. NIMH, BIOL PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. RP NIMH, NEUROSCI CTR ST ELIZABETHS, NEUROPSYCHIAT BRANCH, WASHINGTON, DC 20032 USA. NR 15 TC 11 Z9 14 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 1992 VL 109 IS 1-2 BP 248 EP 250 DI 10.1007/BF02245510 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA JQ592 UT WOS:A1992JQ59200036 PM 1365667 ER PT J AU HAHN, SM WILSON, L KRISHNA, CM LIEBMANN, J DEGRAFF, W GAMSON, J SAMUNI, A VENZON, D MITCHELL, JB AF HAHN, SM WILSON, L KRISHNA, CM LIEBMANN, J DEGRAFF, W GAMSON, J SAMUNI, A VENZON, D MITCHELL, JB TI IDENTIFICATION OF NITROXIDE RADIOPROTECTORS SO RADIATION RESEARCH LA English DT Article ID INACTIVATION; INHIBITION C1 NCI,DATA MANAGEMENT SECT,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SCH MED,MOLEC BIOL,IL-91010 JERUSALEM,ISRAEL. RP HAHN, SM (reprint author), NCI,RADIAT ONCOL BRANCH,RADIOBIOL SECT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 23 TC 73 Z9 75 U1 0 U2 2 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 1992 VL 132 IS 1 BP 87 EP 93 DI 10.2307/3578338 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA JU547 UT WOS:A1992JU54700013 PM 1410280 ER PT J AU MILLER, DL DOPPMAN, JL PETERMAN, SB NIEMAN, LK OLDFIELD, EH CHANG, R AF MILLER, DL DOPPMAN, JL PETERMAN, SB NIEMAN, LK OLDFIELD, EH CHANG, R TI NEUROLOGIC COMPLICATIONS OF PETROSAL SINUS SAMPLING SO RADIOLOGY LA English DT Article DE CATHETERS AND CATHETERIZATION, COMPLICATIONS; CUSHING SYNDROME; SINUSES, DURAL AB Petrosal sinus sampling has been described as an innocuous, essentially risk-free procedure. The authors report on two patients from two different institutions who sustained brain stem injury as a result of petrosal sinus sampling and two other patients in whom brain stem injury was avoided. Major neurologic complications have occurred in only 0.2% of procedures (one of 508) performed at the National Institutes of Health and in 0.5% of a subset of these procedures (one of 184) that were performed with a specially designed petrosal sinus catheter. The cause of these complications is unclear but is presumed to be localized venous hypertension. Tip-deflector catheter-guide-wire systems, if available, are recommended for petrosal sinus sampling. Inadequate data exist to permit recommendation of any other catheter. Brain stem injury is preventable if the catheter is withdrawn at the earliest sign of even a minor, seemingly insignificant problem. Subtle symptoms and signs that may not appear to be neurologic may herald a clinical catastrophe if not heeded. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT RADIOL,WASHINGTON,DC 20007. EMORY UNIV,SCH MED,DEPT RADIOL,ATLANTA,GA 30322. RP MILLER, DL (reprint author), NINCDS,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,BETHESDA,MD 20892, USA. NR 12 TC 97 Z9 98 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 1992 VL 185 IS 1 BP 143 EP 147 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JN608 UT WOS:A1992JN60800027 PM 1523298 ER PT J AU MELNICK, RL AF MELNICK, RL TI MECHANISTIC DATA IN SCIENTIFIC PUBLIC-HEALTH DECISIONS SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Editorial Material RP MELNICK, RL (reprint author), NIEHS,DIV BIOMETRY & RISK ASSESSMENT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD OCT PY 1992 VL 16 IS 2 BP 109 EP 110 DI 10.1016/0273-2300(92)90051-A PG 2 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA JP993 UT WOS:A1992JP99300001 PM 1438993 ER PT J AU MELNICK, RL AF MELNICK, RL TI AN ALTERNATIVE HYPOTHESIS ON THE ROLE OF CHEMICALLY-INDUCED PROTEIN DROPLET (ALPHA-2U-GLOBULIN) NEPHROPATHY IN RENAL CARCINOGENESIS SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID FEMALE FISCHER-344 RATS; ADULT MALE-RATS; UNLEADED GASOLINE; D-LIMONENE; 2,2,4-TRIMETHYLPENTANE-INDUCED NEPHROTOXICITY; REVERSIBLE BINDING; CELL-PROLIFERATION; KIDNEY TUMORS; TUBULAR CELL; EXPOSURE RP MELNICK, RL (reprint author), NIEHS,DIV BIOMETRY & RISK ASSESSMENT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 58 TC 42 Z9 44 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD OCT PY 1992 VL 16 IS 2 BP 111 EP 125 DI 10.1016/0273-2300(92)90052-B PG 15 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA JP993 UT WOS:A1992JP99300002 PM 1279759 ER PT J AU ISONO, M GELLER, HM POLTORAK, M FREED, WJ AF ISONO, M GELLER, HM POLTORAK, M FREED, WJ TI INTRACEREBRAL TRANSPLANTATION OF THE A7 IMMORTALIZED ASTROCYTIC CELL-LINE SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE ASTROCYTE; IMMORTALIZED CELL LINE; BRAIN TRANSPLANTATION; CELL ADHESION MOLECULE; IMMUNOLOGICAL REACTION ID GENETICALLY MODIFIED CELLS; PRECURSOR CELLS; ADHESION MOLECULES; N-CADHERIN; EXPRESSION; BRAIN; ONCOGENE; STRIATUM; NEURONS; VECTOR AB The A7 cell line is an astrocyte-like cell immortalized by SV40 large T antigen, using retroviral-mediated gene transfer. These cells were transplanted into rat brains, and the graft-host interaction was investigated immunohistochemically. The A7 cells survived focally 2, 6 and 8 weeks after transplantation and retained the immunocytochemical properties observed in vitro. No immunological response was observed. GAP-43 and N-cadherin immunoreactivities were not expressed by A7 cells, but were seen in the matrix within the area of the graft and in the surrounding brain tissue. This indicates that A7 cells may stimulate expression of GAP-43 and N-cadherin immunoreactivity by host tissue. Expression of Thy 1.1 was not observed within the graft site after 2 weeks of survival, but 6 and 8 weeks after transplantation Thy 1.1 was observed within the graft area, indicating the possible co-existence of grafted cells and host tissue. Although indirect, these observations suggest that the A7 cells induce changes in host brain, including possible growth or regeneration of host tissue into the graft area. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PHARMACOL,PISCATAWAY,NJ 08854. OI Geller, Herbert/0000-0002-7048-6144 NR 31 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PD OCT PY 1992 VL 4 IS 5 BP 301 EP 309 PG 9 WC Neurosciences SC Neurosciences & Neurology GA JW355 UT WOS:A1992JW35500001 PM 21551661 ER PT J AU OHMAN, KP YUN, JCH KEISER, HR AF OHMAN, KP YUN, JCH KEISER, HR TI INTERACTION OF PROSTAGLANDINS WITH ADENOSINE-DIPHOSPHATE INDUCED INCREASE IN CYTOSOLIC FREE CALCIUM IN HUMAN PLATELETS SO SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION LA English DT Article DE ADENOSINE DIPHOSPHATE; CALCIUM BLOCKADE; CYCLIC AMP; CYTOSOLIC CALCIUM; FORSKOLIN; HUMAN PLATELETS; PLATELET AGGREGATION; PROSTAGLANDINS; QUIN2 ID CYCLIC-AMP; AGGREGATION; ACTIVATION; FORSKOLIN; MEMBRANE AB The interaction of prostaglandins with changes in cytosolic Ca2+ concentration ([Ca2+]) and aggregation of human platelets induced by adenosine diphosphate (ADP) were investigated. Cytosolic [Ca2+] was measured with the fluorescent dye Quin2. Addition of ADP (0.25-2.5-mu-mol l-1) to platelet suspensions produced a dose dependent increase in cytosolic [Ca2+] from a basal level of 51 +/- 1 nmol l-1 to maximum levels exceeding 1-mu-mol l-1 and induced platelet aggregation. Chelation of extracellular calcium with 100-mu-mol l-1 EGTA markedly reduced the increase in cytosolic [Ca2+] induced by 0.25-mu-mol l-1 ADP, while pretreatment with the calcium entry blocker verapamil was without effect. Stimulation of cyclic AMP with prostaglandins (PGD2, PGE1, PGE2, PGI2, but not PGF2-alpha) and forskolin, OT incubation with dibutyryl-cAMP, inhibited the rise in cytosolic [Ca2+] and platelet aggregation following ADP. We conclude that prostaglandins inhibit the increase in cytosolic [Ca2+] and aggregation of human platelets induced by ADP, probably by stimulation of cyclic AMP generation, thereby opposing the mechanism by which ADP increases cytostolic [Ca2+] and subsequently induces platelet aggregation. C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. HOWARD UNIV,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20059. FU NCRR NIH HHS [S06 RR-08016] NR 19 TC 3 Z9 3 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0036-5513 J9 SCAND J CLIN LAB INV JI Scand. J. Clin. Lab. Invest. PD OCT PY 1992 VL 52 IS 6 BP 483 EP 490 DI 10.3109/00365519209090125 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JN380 UT WOS:A1992JN38000006 PM 1329185 ER PT J AU HELANDER, HF RUTGERSSON, K HELANDER, KG PISEGNA, JP GARDNER, JD JENSEN, RT MATON, PN AF HELANDER, HF RUTGERSSON, K HELANDER, KG PISEGNA, JP GARDNER, JD JENSEN, RT MATON, PN TI STEREOLOGIC INVESTIGATIONS OF HUMAN GASTRIC-MUCOSA .2. OXYNTIC MUCOSA FROM PATIENTS WITH ZOLLINGER-ELLISON SYNDROME SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE ENDOCRINE CELLS; ENDOSOMES; GASTRIC MUCOSA; GASTRIN; MORPHOMETRY; OMEPRAZOLE; PARIETAL CELLS; ZOLLINGER-ELLISON SYNDROME ID ENDOCRINE-CELLS; ACID-SECRETION; TERM TREATMENT; LONG-TERM; OMEPRAZOLE; RAT; RANITIDINE; HISTOLOGY; PARIETAL; INTACT AB Biopsy specimens from the oxyntic mucosa were obtained on 210 occasions from 76 patients with the Zollinger-Ellison syndrome (ZES) before and during omeprazole treatment. One-micrometer sections were examined by light microscopy, and in 5% linear hyperplasia of endocrine cells was observed. Morphometry was carried out in 91 of the specimens and showed a significant increase of the mean endocrine cell density in comparison with both young, healthy subjects and patients suffering from active peptic ulcer disease (PUD). No metaplasia. dysplasia, or neoplasia was detected in patients with ZES, and the mean mucosal thickness and parietal cell density remained normal. The parietal cells often displayed endosome-like structures, and occasionally there were lingulate cytoplasmic projections into the gland lumen. Electron microscopic morphometry was carried out in specimens from nine patients with ZES and did not show any significant differences in the parietal cells in comparison with healthy subjects. C1 ASTRA HASSLE AB,DEPT MED,S-43183 MOLNDAL,SWEDEN. NIH,BETHESDA,MD 20892. RP HELANDER, HF (reprint author), ASTRA HASSLE AB,DEPT CELL BIOL,S-43183 MOLNDAL,SWEDEN. NR 29 TC 28 Z9 28 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD OCT PY 1992 VL 27 IS 10 BP 875 EP 883 DI 10.3109/00365529209000157 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JT621 UT WOS:A1992JT62100012 PM 1439541 ER PT J AU JACOBSEN, SEW SMELAND, EB RUSCETTI, FW KELLER, JR AF JACOBSEN, SEW SMELAND, EB RUSCETTI, FW KELLER, JR TI TUMOR NECROSIS FACTOR-A (TNF-A) DIRECTLY AND INDIRECTLY REGULATES HEMATOPOIETIC PROGENITOR-CELL PROLIFERATION - ROLE OF CSF RECEPTOR MODULATION SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 NORWEGIAN RADIUM HOSP,IMMUNOL LAB,OSLO 3,NORWAY. NCI,FREDERICK CANC RES FACIL,LMI,BRMP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES FACIL,PRI DYNCORP,BCDP,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD OCT PY 1992 VL 36 IS 4 BP 631 EP 631 PG 1 WC Immunology SC Immunology GA JQ317 UT WOS:A1992JQ31700076 ER PT J AU VINEIS, P BLAIR, A AF VINEIS, P BLAIR, A TI PROBLEMS AND PERSPECTIVES IN THE IDENTIFICATION OF NEW OCCUPATIONAL CARCINOGENS SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE ATTRIBUTABLE RISKS; BIOMARKERS; EPIDEMIOLOGY; REVIEW ID CASE-REFERENT; CANCER; ASSOCIATIONS; MONTREAL; SITES; PROPORTION; MORTALITY; WORKERS; MALES; LUNG AB Occupational studies have played a major role in the identification of chemical carcinogens. There still remain, however, substances and occupations that deserve further evaluation. The more careful control of potentially hazardous exposures in most developed countries has necessitated a change in the conduct of epidemiologic investigations. The lowering of exposures and the lack of a simple correspondence between specific exposures and one or a few jobs underscores the need for careful reconstruction of historical exposures. The most successful reconstructions will include the integration of monitoring data, historical information on work histories and work practices, and use of biochemical markers. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,BETHESDA,MD 20892. UNIV TURIN,I-10124 TURIN,ITALY. RP VINEIS, P (reprint author), MAIN HOSP,CANC EPIDEMIOL UNIT,VIA SANTENA 7,I-10126 TURIN,ITALY. NR 29 TC 1 Z9 1 U1 1 U2 1 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD OCT PY 1992 VL 18 IS 5 BP 273 EP 277 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JP708 UT WOS:A1992JP70800001 PM 1439652 ER PT J AU HUANG, SZ REN, ZR ZENG, YT ZENG, FY RODGERS, GP SCHECHTER, AN AF HUANG, SZ REN, ZR ZENG, YT ZENG, FY RODGERS, GP SCHECHTER, AN TI STUDY OF THE RNA SPLICING DEFECT IN THE COMMON CHINESE BETA-THALASSEMIA GENE, IVS-II NT 654 C-]T BY USING MESSENGER RNA/PCR SO SCIENCE IN CHINA SERIES B-CHEMISTRY LA English DT Article DE THALASSEMIA; MESSENGER RNA; POLYMERASE CHAIN REACTION; SPLICING DEFECT ID MOLECULAR-BASIS; GLOBIN GENE; DNA; MUTATIONS AB With direct sequencing of the amplified cDNA, we analysed the transcript and mRNA splicing defect in a common Chinese beta-thalassemia mutant (IVS-II nt. 654 C --> T). The result shows that this mutant gene would not only produce abnormally processed beta-globin mRNA, but also transcribes a small amount of normally spliced mRNA, hence leading to beta+ thalassemia. The method described herein provides a simple and sensitive approach to the studies of gene expression and molecular defects in genetic diseases at transcriptional level. C1 NIDDKD,BETHESDA,MD 20892. RP HUANG, SZ (reprint author), SHANGHAI CHILDRENS HOSP,SHANGHAI INST MED GENET,SHANGHAI 200040,PEOPLES R CHINA. FU NHLBI NIH HHS [HL-29623] NR 16 TC 0 Z9 0 U1 0 U2 0 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1001-652X J9 SCI CHINA SER B JI Sci. China Ser. B-Chem. PD OCT PY 1992 VL 35 IS 10 BP 1232 EP 1237 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA JY772 UT WOS:A1992JY77200011 PM 1285849 ER PT J AU VENER, KJ REDDY, A AF VENER, KJ REDDY, A TI TIMED TREATMENT OF THE ARTHRITIC DISEASES - A REVIEW AND HYPOTHESIS SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE RHEUMATOID ARTHRITIS; BIOLOGICAL RHYTHMS; CHRONOPHARMACOLOGY; METHOTREXATE ID LOW-DOSE METHOTREXATE; RHEUMATOID-ARTHRITIS; CIRCADIAN VARIATION; DIURNAL-VARIATION; PERIPHERAL-BLOOD; HEALTHY-SUBJECTS; SHIFT-WORK; CANCER-PATIENTS; RHYTHMS; INDOMETHACIN C1 NIAMSD,BETHESDA,MD. NR 150 TC 2 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 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD OCT PY 1992 VL 22 IS 2 BP 83 EP 97 DI 10.1016/0049-0172(92)90002-U PG 15 WC Rheumatology SC Rheumatology GA JT728 UT WOS:A1992JT72800002 PM 1439846 ER PT J AU NEWMAN, JF GIFT, HC AF NEWMAN, JF GIFT, HC TI REGULAR PATTERN OF PREVENTIVE DENTAL SERVICES - A MEASURE OF ACCESS SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE DENTAL UTILIZATION; PREVENTIVE SERVICES; REGULAR CARE ID UNITED-STATES; MEDICAL-CARE AB Having a regular pattern of care should be an indicator of access to and periodic use of preventive and health maintenance services. The analyses reported in this study are intended to provide a better understanding of the factors related to having a regular pattern of preventive dental care. The data were collected in 1981 as part of a U.S. household survey, 'A Study of Dental Health Related and Process Outcomes Associated with Prepaid Dental Care', the most comprehensive cross-sectional data base available in dentistry. Descriptive analyses of a constructed variable, representing perceived and realized access and a preventive orientation, indicate that 53% of the population had a regular pattern of preventive care. Those with a regular pattern of care were more likely to be white, younger, have dental insurance, have no cost barriers, have more than 12 years of education, be dentate, have no perceived symptoms, and no fear of pain. Logistic regressions indicated that there was an increased probability of having a regular pattern of preventive care if individuals had no economic access problems, had positive attitudes, had higher income, reported few oral symptoms, and were non-Black. Overall, the descriptive models used suggested that individuals with resources in the form of finances and education, and a sense of self-efficacy as expressed in attitudes toward oral health, had the greatest probability of having a regular pattern of preventive care. C1 NIDR,DIS PREVENT & HLTH PROMOT BRANCH,WESTWOOD BLDG,ROOM 534,BETHESDA,MD 20892. GEORGIA STATE UNIV,INST HLTH ADM,ATLANTA,GA 30303. NR 15 TC 52 Z9 52 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD OCT PY 1992 VL 35 IS 8 BP 997 EP 1001 DI 10.1016/0277-9536(92)90239-M PG 5 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA JQ805 UT WOS:A1992JQ80500006 PM 1411707 ER PT J AU ROSSOUW, JE LAITUNG, MT JOOSTE, PL WEIGHT, MJ BENADE, AJS AF ROSSOUW, JE LAITUNG, MT JOOSTE, PL WEIGHT, MJ BENADE, AJS TI ALCOHOL INTAKE IN RELATION TO LIPIDS, LIPOPROTEINS AND BLOOD-PRESSURE SO SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article ID CORONARY-ARTERY DISEASE; HIGH-DENSITY LIPOPROTEINS; APOLIPOPROTEIN-A-I; U-SHAPED CURVE; HEART-DISEASE; MYOCARDIAL-INFARCTION; SUBFRACTIONS; PLASMA; CHOLESTEROL; MORTALITY AB A cross-sectional population study of 655 men and 731 women was undertaken to evaluate the association between the level of alcohol intake, the level of high-density lipoprotein cholesterol (HDL-C) and its subfractions, and blood pressure in men and women in different age groups (20 - 44 and 45 - 64 years). Habitual alcohol intake was significantly related to higher levels of HDL-C in both men and women. In the case of men both HDL2-C and HDL3-C levels were raised, while in women this rise was restricted almost entirely to HDL2-C. Plasma apolipoprotein A-I and A-II levels were elevated in men who drank, but not in women. In both, triglyceride and blood pressure levels were raised with habitual alcohol intake, and the increases in HDL subfractions and blood pressure levels became more marked with increasing age in both men and women. Recent alcohol intake had less effect on all the variables except blood pressure. We conclude that both HDL3-C and HDL2-C contribute to the rise in HDL-C levels that accompanies alcohol use, notwithstanding differences in the responses of the sexes. A regular alcohol intake is more likely to be beneficial and some of the positive or protective aspects of alcohol consumption could be reduced by the adverse changes in triglycerides and blood pressure levels. C1 S AFRICAN MRC,INST BIOSTAT,PAROWVALLEI,SOUTH AFRICA. S AFRICAN MRC,NATL RES PROGRAMME NUTR INTERVENT,PAROWVALLEI,SOUTH AFRICA. RP ROSSOUW, JE (reprint author), NHLBI,LIPID METAB ATHEROGENESIS BRANCH,BETHESDA,MD 20892, USA. NR 33 TC 7 Z9 7 U1 1 U2 2 PU MED ASSOC S AFRICA PI JOHANNESBURG PA MED HOUSE CENTRAL SQ 7430 PINELANDS JOHANNESBURG, SOUTH AFRICA SN 0038-2469 J9 S AFR MED J JI S. Afr. Med. J. PD OCT PY 1992 VL 82 IS 4 BP 246 EP 250 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JT054 UT WOS:A1992JT05400013 PM 1411821 ER PT J AU ROTHMAN, RB AF ROTHMAN, RB TI A REVIEW OF THE ROLE OF ANTI-OPIOID PEPTIDES IN MORPHINE-TOLERANCE AND DEPENDENCE SO SYNAPSE LA English DT Article DE OPIOID RECEPTORS; OPIOID DEPENDENCE; CCK-8; FRMF-NH2 ID GUINEA-PIG ILEUM; DYNORPHIN-A 1-17; RAT SPINAL-CORD; MELANOCYTE-STIMULATING HORMONE; THYROTROPIN RELEASING HORMONE; ADENYLATE-CYCLASE ACTIVITY; MULTIPLE OPIATE RECEPTORS; BETA-ENDORPHIN ANALGESIA; FREELY MOVING RATS; MOUSE VAS-DEFERENS AB Studies on the mechanisms of tolerance and dependence have mostly focused on changes at the receptor level. These experiments, conducted with model systems ranging from clonal cell lines to whole animals, have identified a number of important adaptive mechanisms which occur at the receptor level. However, none of these adaptive mechanisms can completely account for the phenomena which serve to define the state of morphine tolerance and dependence, especially the observation that as an animal becomes more tolerant to morphine, less naloxone is required to trigger withdrawal. The data reviewed in this paper provide strong support for the hypothesis that the brain synthesizes and secretes neuropeptides which act as part of a homeostatic system to attenuate the effects of morphine and endogenous opioid peptides. According to this model, administration of morphine releases anti-opioid peptides (AOP), which then attenuate the effects of morphine. As more morphine is given, more AOP are released, thereby producing tolerance to the effects of morphine. Cessation of morphine administration, or administration of naloxone, produces a relative excess of anti-opioid, which is in part responsible for the withdrawal syndrome. Since endogenous and exogenous antagonists might together produce synergistic effects, less naloxone might be required to trigger withdrawal in the presence of higher levels of AOPs. Although the study of AOP is in its infancy, a deeper understanding of the central nervous system (CNS) anti-opioid systems may lead to new treatments for chronic pain, substance abuse, and psychiatric disorders. RP ROTHMAN, RB (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL LAB,BALTIMORE,MD 21224, USA. NR 109 TC 150 Z9 151 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 0887-4476 J9 SYNAPSE JI Synapse PD OCT PY 1992 VL 12 IS 2 BP 129 EP 138 DI 10.1002/syn.890120206 PG 10 WC Neurosciences SC Neurosciences & Neurology GA JN626 UT WOS:A1992JN62600005 PM 1362289 ER PT J AU GONZALEZ, FJ CRESPI, CL CZERWINSKI, M GELBOIN, HV AF GONZALEZ, FJ CRESPI, CL CZERWINSKI, M GELBOIN, HV TI ANALYSIS OF HUMAN CYTOCHROME-P450 CATALYTIC ACTIVITIES AND EXPRESSION SO TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE HUMAN CYTOCHROME-P-450; CATALYTIC ACTIVITY; CDNA EXPRESSION; CHEMICAL CARCINOGEN; RNASE PROTECTION ID SUPERFAMILY AB Cytochromes P450 are a large group of membrane-associated heme protein monooxygenases, most of which are responsible for metabolizing foreign compounds. Chemical carcinogens, which are ingested or absorbed into the body as inert forms, are metabolically activated by P450s to electrophilic metabolites capable of binding to and mutating DNA. Different P450 forms axe responsible for activation of the various classes of chemical carcinogens including the axylamines, polycyclic aromatic hydrocarbons, nitrosamines and aflatoxins. Thus, the cellular constituency and levels of P450s could determine the fate of a particular carcinogen and the risk of humans to exposure. To study the catalytic activities of human P450s, human P450 cDNAs were cloned and expressed into active enzymes using cultured cells. By both transient and stable cDNA expression systems, several human P450s were found to be capable of metabolically-activating the human hepatocarcinogen aflatoxin B1. These cDNA expression systems can also be used to determine whether an unknown chemical will be activated by a human P450 and thus be toxic or mutagenic in humans. To assess the extent of interindividual variation in P450 expression, probes developed from P450 cDNAs are being used to quantify levels of P450 mRNAs in various human tissues. Studies using RNase protection revealed that the closely related CYP2B6 and CYP2B7 mRNAs could be independently quantified in liver and lung, respectively. This procedure can be used to examine expression of different P450 genes in banks of human tissue specimens. C1 GENTEST CORP, WOBURN, MA USA. RP GONZALEZ, FJ (reprint author), NCI, MOLEC CARCINOGENESIS LAB, BLDG 37, ROOM 3E24, BETHESDA, MD 20892 USA. NR 9 TC 18 Z9 18 U1 0 U2 1 PU TOHOKU UNIV MEDICAL PRESS PI SENDAI PA 2-1, SEIRYO-MACHI, AOBA-KU, SENDAI, MIYAGI 980-8575, JAPAN SN 0040-8727 EI 1349-3329 J9 TOHOKU J EXP MED JI Tohoku J. Exp. Med. PD OCT PY 1992 VL 168 IS 2 BP 67 EP 72 DI 10.1620/tjem.168.67 PG 6 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA KY786 UT WOS:A1992KY78600001 PM 1306334 ER PT J AU FRICKE, W AUGUSTYNIAK, L LAWRENCE, D BROWNSTEIN, A KRAMER, A EVATT, B AF FRICKE, W AUGUSTYNIAK, L LAWRENCE, D BROWNSTEIN, A KRAMER, A EVATT, B TI HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION DUE TO CLOTTING FACTOR CONCENTRATES - RESULTS OF THE SEROCONVERSION SURVEILLANCE PROJECT SO TRANSFUSION LA English DT Article ID HEMOPHILIA-B; SEROPREVALENCE; TRANSMISSION AB From 1987 to the present, the Seroconversion Surveillance Project has provided the means by which to monitor the risk of transmission of human immunodeficiency virus (HIV) by clotting factor concentrates. One hundred thirty-one hemophilia treatment centers in the United States are contacted regularly, and data on HIV testing of patients are collected. To date, 4366 (46.0%) of 9496 patients have been reported to be seropositive, and 37 new seroconversions have been identified. Nine of these have met the Centers for Disease Control criteria for seroconversion while the patient was taking factor concentrate. None of the nine seroconversions were due to concentrates that had been treated to inactivate viruses and made from plasma that had been tested for HIV antibody. These results indicate that there is a high prevalence of seropositivity in affected patient groups, but that the risk of HIV infection from currently available clotting factor concentrates is extremely low. C1 NATL HEMOPHILIA FDN,NEW YORK,NY. CTR DIS CONTROL,ATLANTA,GA 30333. RP FRICKE, W (reprint author), NIAID,CTR BIOL EVALUAT & RES FOOD & DRUG ADM,HFB-440,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU PHS HHS [223-89-1005] NR 11 TC 24 Z9 24 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 BP 707 EP 709 DI 10.1046/j.1537-2995.1992.32893032095.x PG 3 WC Hematology SC Hematology GA JV169 UT WOS:A1992JV16900004 PM 1412676 ER PT J AU SLOAND, E KLEIN, HG AF SLOAND, E KLEIN, HG TI WHITE CELL REDUCTION IN PLATELET CONCENTRATES SO TRANSFUSION LA English DT Letter RP SLOAND, E (reprint author), NIH,DEPT TRANSFUS MED,BLDG 31,ROOM 5A-21,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 BP 787 EP 787 DI 10.1046/j.1537-2995.1992.32893032112.x PG 1 WC Hematology SC Hematology GA JV169 UT WOS:A1992JV16900021 PM 1285789 ER PT J AU CARTER, CS GUTIERREZ, RH MAY, FF YU, MY LEITMAN, SF KLEIN, HG CHANG, L ANDERSON, WF CULVER, KW BLAESE, RM AF CARTER, CS GUTIERREZ, RH MAY, FF YU, MY LEITMAN, SF KLEIN, HG CHANG, L ANDERSON, WF CULVER, KW BLAESE, RM TI PREPARATION OF ADENOSINE-DEAMINASE (ADA) CORRECTED T-CELLS FOR USE IN GENE-THERAPY SO TRANSFUSION LA English DT Meeting Abstract C1 CLIN CTR,BETHESDA,MD. NHLBI,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 SU S BP S46 EP S46 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800173 ER PT J AU CHANG, L ANDERSON, WF CARTER, CS KLEIN, HG CULVER, KW BLAESE, RM AF CHANG, L ANDERSON, WF CARTER, CS KLEIN, HG CULVER, KW BLAESE, RM TI VARIABILITY IN GROWTH MEDIA USED FOR CULTURE AND EXPANSION OF LYMPHOCYTES IN GENE-THERAPY TRIALS SO TRANSFUSION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 SU S BP S71 EP S71 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800266 ER PT J AU CONRYCANTILENA, C VILADOMIU, L MELPOLDER, J JETT, B MOSS, T ALTER, HJ GIBBLE, J NESS, P AF CONRYCANTILENA, C VILADOMIU, L MELPOLDER, J JETT, B MOSS, T ALTER, HJ GIBBLE, J NESS, P TI RISK-FACTORS FOR HEPATITIS-C VIRUS-INFECTION IN A UNITED-STATES URBAN BLOOD-DONOR POPULATION SO TRANSFUSION LA English DT Meeting Abstract C1 CHESAPEAKE & POTOMAC REG,BALTIMORE,MD. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 SU S BP S46 EP S46 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800170 ER PT J AU DAVEY, RJ AF DAVEY, RJ TI CHARACTERISTICS OF TRANSFUSION MEDICINE FELLOWSHIP PROGRAMS SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 SU S BP S93 EP S93 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800350 ER PT J AU DEMAS, JE KLEIN, HG CARTER, GR AF DEMAS, JE KLEIN, HG CARTER, GR TI CAMPUS RECRUITMENT - MINORITY KIDS FOR MARROW SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 SU S BP S82 EP S82 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800306 ER PT J AU LEITMAN, SF SILBERSTEIN, L FAIRMAN, RM LEWIS, DF AF LEITMAN, SF SILBERSTEIN, L FAIRMAN, RM LEWIS, DF TI USE OF A RADIATION-SENSITIVE FILM LABEL IN THE QUALITY-CONTROL OF IRRADIATED BLOOD COMPONENTS SO TRANSFUSION LA English DT Meeting Abstract C1 ISP,WAYNE,NJ. NIH,BETHESDA,MD 20892. HOSP UNIV PENN,PHILADELPHIA,PA 19104. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 SU S BP S4 EP S4 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800010 ER PT J AU METTER, KJ LOPEZPLAZA, I LEITMAN, SF AF METTER, KJ LOPEZPLAZA, I LEITMAN, SF TI RECRUITING THE HISPANIC MARROW DONOR SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 SU S BP S93 EP S93 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800351 ER PT J AU SUDA, BA LEITMAN, SF DAVEY, RJ AF SUDA, BA LEITMAN, SF DAVEY, RJ TI IRRADIATION OF RED-CELLS PRIOR TO LONG-TERM FROZEN STORAGE SO TRANSFUSION LA English DT Meeting Abstract C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1992 VL 32 IS 8 SU S BP S70 EP S70 PG 1 WC Hematology SC Hematology GA JW378 UT WOS:A1992JW37800263 ER EF