FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Vicari, AP Figueroa, DJ Hedrick, JA Foster, JS Singh, KP Menon, S Copeland, NG Gilbert, DJ Jenkins, NA Bacon, KB Zlotnik, A AF Vicari, AP Figueroa, DJ Hedrick, JA Foster, JS Singh, KP Menon, S Copeland, NG Gilbert, DJ Jenkins, NA Bacon, KB Zlotnik, A TI TECK: A novel CC chemokine specifically expressed by thymic dendritic cells and potentially involved in T cell development SO IMMUNITY LA English DT Article ID LUNG ALLERGIC INFLAMMATION; SIGNAL SEQUENCE TRAP; MOLECULAR-CLONING; ENDOTHELIAL-CELLS; LINKAGE MAP; TNF-ALPHA; B-CELLS; GM-CSF; MOUSE; PROTEIN AB A novel CC chemokine was identified in the thymus of mouse and human and was designated TECK (thymus-expressed chemokine). TECK has weak homology to other CC chemokines and maps to mouse chromosome 8. Besides the thymus, mRNA encoding TECK was detected at substantial levels in the small intestine and at low levels in the liver. The source of TECK in the thymus was determined to be thymic dendritic cells; in contrast, bone marrow-derived dendritic cells do not express TECK. The murine TECK recombinant protein showed chemotactic activity for activated macrophages, dendritic cells, and thymocytes. We conclude that TECK represents a novel thymic dendritic cell-specific CC chemokine that is possibly involved in T cell development. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP Vicari, AP (reprint author), DNAX RES INST MOL & CELLULAR BIOL INC,901 CALIF AVE,PALO ALTO,CA 94304, USA. RI Zlotnik, Albert/C-3791-2011 NR 57 TC 200 Z9 209 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 1997 VL 7 IS 2 BP 291 EP 301 DI 10.1016/S1074-7613(00)80531-2 PG 11 WC Immunology SC Immunology GA XT492 UT WOS:A1997XT49200012 PM 9285413 ER PT J AU Rastogi, VK Chary, KVR Govil, G Howard, FB Miles, HT AF Rastogi, VK Chary, KVR Govil, G Howard, FB Miles, HT TI NMR structural characterisation of a hairpin DNA with two-base loop: Solution conformation of d-GGTACIAGTACC SO INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS LA English DT Article ID D-GGTACGCGTACC; DEOXYINOSINE; MACROMOLECULES; PROBE; H-1 AB An inosine-adenosine mismatched base-pair oligonucleotide, d-GGTACIAGTACC has been studied by H-1 and P-31 NMR spectroscopy. Almost complete H-1 and P-31 resonance assignments of the oligomer at 0.90 mM concentration and 310 K have been achieved. NMR results demonstrate that the oligomer adopts a hairpin conformation, which has a structure with two purines I6 and A7 forming a two-base loop on a B-DNA stem. Stacking is continued on the 5'-side of the loop, with the I6 stacked upon C5. The base A7, on the 3'-side of the loop stacks partially with I6. All the bases are in anti conformation with respect to their respective sugar moiety. C1 TATA INST FUNDAMENTAL RES,CHEM PHYS GRP,BOMBAY 400005,MAHARASHTRA,INDIA. NIDDKD,NIH,BETHESDA,MD 20892. NR 21 TC 1 Z9 1 U1 0 U2 1 PU COUNCIL SCIENTIFIC INDUSTRIAL RESEARCH PI NEW DELHI PA PUBL & INFO DIRECTORATE, NEW DELHI 110012, INDIA SN 0301-1208 J9 INDIAN J BIOCHEM BIO JI Indian J. Biochem. Biophys. PD AUG PY 1997 VL 34 IS 4 BP 329 EP 335 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YG938 UT WOS:A1997YG93800001 PM 9491641 ER PT J AU Tian, JH Kumar, S Kaslow, DC Miller, LH AF Tian, JH Kumar, S Kaslow, DC Miller, LH TI Comparison of protection induced by immunization with recombinant proteins from different regions of merozoite surface protein 1 of Plasmodium yoelii SO INFECTION AND IMMUNITY LA English DT Article ID AOTUS MONKEYS; FALCIPARUM MALARIA; CHALLENGE; FRAGMENT; ANTIGEN AB Vaccination with native full-length merozoite surface protein 1 (MSPI) or with recombinant C-terminal peptides protects mice against lethal challenge with virulent malaria parasites, To determine whether other regions of MSPI can also induce protection, Plasmodium yoelii MSPI was divided into four separate regions, Each was expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST), The N-terminal fragment began after the cleavage site for the signal sequence and ended in the region comparable to the cleavage site for the C terminus of the 82-kDa peptide of Plasmodium falciparum. This expressed protein was 30 kDa smaller than the predicted peptide, One peptide from the middle region was produced, and the C terminus consisted of a 42-kDa fragment corresponding to the analogous peptide of P, falciparum and a 19-kDa fragment that extended 37 amino acids in the amino-terminal direction beyond the probable cleavage site, To test protection of mice against lethal P, yoelii challenge, three mouse strains (CAF1, BALB/c, and A/J) were vaccinated with each of the four recombinant proteins of MSP1, Mice vaccinated with the C-terminal 19-kDa protein were highly protected (described previously), as were those vaccinated with the 42-kDa protein that contained the 19-kDa fragment, The N-terminally expressed fragment of P, yoelii was not full length because of proteolytic cleavage in E. coli, The GST-82-kDa partial fragments induced some immunity, but the surviving mice still had high parasitemias, Vaccination with the peptide from the middle region of MSP1 gave minimal to no protection, Therefore, in addition to the C-terminal 19- and 42-kDa proteins, the only other fragment to give protection was the 82-kDa protein, The protection induced by the truncated 82-kDa protein was minimal compared with that of the C-terminal fragments. C1 NIAID,LPD,NIH,BETHESDA,MD 20892. NR 18 TC 40 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1997 VL 65 IS 8 BP 3032 EP 3036 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XM714 UT WOS:A1997XM71400006 PM 9234750 ER PT J AU NardelliHaefliger, D Roden, RBS Benyacoub, J Sahli, R Kraehenbuhl, JP Schiller, JT Lachat, P Potts, A DeGrandi, P AF NardelliHaefliger, D Roden, RBS Benyacoub, J Sahli, R Kraehenbuhl, JP Schiller, JT Lachat, P Potts, A DeGrandi, P TI Human papillomavirus type 16 virus-like particles expressed in attenuated Salmonella typhimurium elicit mucosal and systemic neutralizing antibodies in mice SO INFECTION AND IMMUNITY LA English DT Article ID MAJOR CAPSID PROTEIN; FEMALE REPRODUCTIVE-TRACT; SECRETORY IMMUNE-SYSTEM; HIGH-LEVEL EXPRESSION; L1 PROTEIN; LYMPHOID-TISSUE; VACCINIA VIRUS; HUMAN SERA; IMMUNIZATION; INFECTION AB Attenuated strains of Salmonella are attractive live vaccine candidates for eliciting mucosal as well as systemic immune responses, The ability to induce immune responses in the reproductive tract may be critical for the effectiveness of a prophylactic vaccine against genital human papillomaviruses (HPV), which are important etiologic agents in the development of cervical cancer, To examine the potential of a live Salmonella-based vaccine to prevent genital HPV infection, the L1 major capsid protein from HPV type 16 (HPV16) was constitutively expressed in the PhoP(c) strain of Salmonella typhimurium. As demonstrated by electron microscopy, the L1 protein expressed in these bacteria assembled into virus-like particles (VLPs) that resemble authentic papillomavirus virions, This is the first demonstration that papillomavirus VLPs ran self-assemble in prokaryotes, BALB/c mice were immunized with the HPV16 L1 recombinant PhoP(c) strain by the oral and nasal routes, Despite a low stability of the L1-espressing plasmid in vivo, a double nasal immunization was effective in inducing L1-specific serum antibodies that recognized mainly native, but not disassembled, VLPs. These antibodies effectively neutralized HPV16 pseudotyped virions in an in vitro infectivity assay. Conformationally dependent anti-VLP immunoglobulin A (IgA) and IgG were also detected in oral and vaginal secretions, indicating that potentially protective antibody responses were elicited at mucosal sites, Recombinant attenuated Salmonella expressing HPV capsids may represent a promising vaccine candidate against genital HPV infection. C1 CHU VAUDOIS,DEPT GYNECOL,CH-1011 LAUSANNE,SWITZERLAND. CHU VAUDOIS,INST MICROBIOL,CH-1011 LAUSANNE,SWITZERLAND. UNIV LAUSANNE,INST BIOCHEM,CH-1066 EPALINGES,SWITZERLAND. SWISS INST EXPT CANC RES,CH-1066 EPALINGES,SWITZERLAND. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 46 TC 113 Z9 120 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1997 VL 65 IS 8 BP 3328 EP 3336 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XM714 UT WOS:A1997XM71400050 PM 9234794 ER PT J AU Gordon, VM Rehemtulla, A Leppla, SH AF Gordon, VM Rehemtulla, A Leppla, SH TI A role for PACE4 in the proteolytic activation of anthrax toxin protective antigen SO INFECTION AND IMMUNITY LA English DT Article ID PSEUDOMONAS EXOTOXIN-A; DIPHTHERIA-TOXIN; PROPROTEIN CONVERTASE; PROCESSING ENZYMES; BACTERIAL TOXINS; LETHAL FACTOR; CELL-SURFACE; FURIN; CLEAVAGE; PROTEASE AB Several bacterial protein toxins require activation by eukaryotic proteases, Previous studies have shown that anthrax toxin protective antigen (PA), Pseudomonas exotoxin A (PE), and diphtheria toxin (DT) are cleaved by furin C-terminal to the sequences RKKR, RQPR, and RVRR, respectively, Because furin-deficient cells retain some sensitivity to PA and DT, it is evident that other cellular proteases can activate these toxins, Whereas furin has been shown to require arginine residues at positions -1 and -4 for substrate recognition, another protease with an activity which could substitute for furin in toxin activation, the furin-related protease PACE4, requires basic residues in the -1, -2, and -4 positions of the substrate sequence; To examine the relative roles of furin and PACE4 in toxin activation, we used furin-deficient CHO cells (FD11 cells) transfected with either the furin (FD11/furin cells) or PACE4 (FD11/PACE4 cells) gene, Mutant PA proteins containing the cleavage sequence RAAR or KR were cytotoxic toward cells expressing only PACE4, In vitro cleavage data demonstrated that PACE4 can recognize RAAR and, to a much lesser extent, KR and Rk, When extracts from PACE4-transfected cells were used as a source of proteases, PACE4 had minimal activity, indicating that it had been partially inactivated or did not remain associated with the cell membranes, Cleavage of iodinated PA containing the sequence RKKR or RAAR was detected on the surface of all cell types tested, but cleavage of a dibasic sequence was detected only intracellularly and only in cells that expressed furin or PACE4. The data provide evidence that PACE4 is present at the exterior of cells, that it plays a role in the proteolytic activation of anthrax toxin PA, and that PACE4 can activate substrates at the sequence RAAR or KR. C1 UNIV MICHIGAN,DIV CANC BIOL,ANN ARBOR,MI 48109. RP Gordon, VM (reprint author), NIDR,MICROBIAL ECOL LAB,NIH,BLDG 30,ROOM 304,30 CONVENT DR MSC 4350,BETHESDA,MD 20892, USA. NR 27 TC 37 Z9 37 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1997 VL 65 IS 8 BP 3370 EP 3375 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XM714 UT WOS:A1997XM71400055 PM 9234799 ER PT J AU Smith, MC Pendleton, CD Maher, VE Kelley, MJ Carbone, DP Berzofsky, JA AF Smith, MC Pendleton, CD Maher, VE Kelley, MJ Carbone, DP Berzofsky, JA TI Oncogenic mutations in ras create HLA-A2.1 binding peptides but affect their extracellular antigen processing SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE class I MHC binding; epitopes; oncogene; proteolysis ID CYTOTOXIC T-LYMPHOCYTES; CLASS-I MOLECULES; DENDRITIC CELLS; MONOCLONAL-ANTIBODY; SYNTHETIC PEPTIDES; P21 RAS; EPITOPES; PROTEIN; IDENTIFICATION; INDUCTION AB Point mutations in oncogene products such as ras may create neoantigenic determinants recognizable by T lymphocytes as tumor antigens, that could be marshalled to eliminate a tumor by inducing specific cytotoxic T lymphocytes (CTL) with an appropriate vaccine. Peptide-pulsed dendritic cells are a promising new approach to cancer vaccines. For such an approach to work, the determinant must be appropriately processed to the right size fragment and be presented by an appropriate HLA molecule. We have investigated both of these issues for a series of ras codon 12 and 13 point mutations that contain sequences predicted to bind to HLA-A2.1, the most common class I HLA molecule. We find that not only do the different mutations affect binding to HLA-A2.1, but also they affect extracellular antigen processing in two ways: by influencing the trimming of flanking residues from the longer sequence and by influencing the susceptibility of the optimal decamer to further proteolytic degradation. The influence of internal residues on cleavage of flanking residues downstream demonstrates the importance of distant interactions between separated amino acid side chains and/or conformational effects in determining antigen processing. These results may be important in designing an effective vaccine to induce mutant ras-specific tumor immunity. C1 NCI,MOL IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,NIH,BETHESDA,MD 20892. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,VANDERBILT CANC CTR,NASHVILLE,TN 37232. OI Kelley, Michael/0000-0001-9523-6080 NR 57 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD AUG PY 1997 VL 9 IS 8 BP 1085 EP 1093 DI 10.1093/intimm/9.8.1085 PG 9 WC Immunology SC Immunology GA XP912 UT WOS:A1997XP91200003 PM 9263005 ER PT J AU VandenBrule, FA Bellahcene, A Jackers, P Liu, FT Sobel, ME Castronovo, V AF VandenBrule, FA Bellahcene, A Jackers, P Liu, FT Sobel, ME Castronovo, V TI Antisense galectin-3 alters thymidine incorporation in human MDA-MB435 breast cancer cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE breast cancer; galectin-3; proliferation; antisense ID CARBOHYDRATE-BINDING PROTEIN-35; NUCLEAR-LOCALIZATION; COLON-CARCINOMA; LECTIN; EXPRESSION; RNA; IDENTIFICATION; MAC-2; CDNA; TRANSCRIPTION AB Galectin-3 is a 30-kDa galactose-binding protein member of the galectin family. Galectin-3 is involved in multiple intracellular and extracellular biological functions, e.g. interactions with laminin and with nucleic acids. This latter property is consistent with the presence of 3. serum-response factor-like domain at the amino-terminal part of the protein. Galectin-3 expression is upregulated during serum-mediated induction of proliferation. In order to examine the role of galectin-3 in breast cancer cell proliferation, we examined in this study the influence of antisense galectin-3 complementary DNA stable transfection on the in vitro thymidine incorporation of human breast cancer MDA-MB435 cells. Two stable transfectants, clones 5.24 and 5.29, were selected based both on the presence of a complete CMV promoter-antisense galectin-3 cDNA cassette as assayed by polymerase chain reaction, and on efficient down-regulation of galectin-3 protein expression as determined by Western blotting. Thymidine incorporation experiments showed that both clones were characterized by significantly decreased values of DNA incorporation compared to wild-type transfectants (55 to 68%, and 71 to 82% of the control clone values). Our data demonstrate for the first time that galectin-3 decreases thymidine incorporation in breast cancer cells. The mechanism underlying this property of galectin-3 and its importance during breast cancer development remain to be elucidated. C1 LA JOLLA INST ALLERGY & IMMUNOL,SAN DIEGO,CA 92121. NCI,MOL PATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892. RP VandenBrule, FA (reprint author), UNIV LIEGE,METASTASIS RES LAB,PATHOL B23,SART TILMAN,B-4000 LIEGE 1,BELGIUM. NR 26 TC 11 Z9 11 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 1997 VL 11 IS 2 BP 261 EP 264 PG 4 WC Oncology SC Oncology GA XL048 UT WOS:A1997XL04800008 PM 21528209 ER PT J AU Khachik, F Bernstein, PS Garland, DL AF Khachik, F Bernstein, PS Garland, DL TI Identification of lutein and zeaxanthin oxidation products in human and monkey retinas SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT 11th International Symposium on Carotenoids CY AUG 18-23, 1996 CL LEIDEN, NETHERLANDS SP Int Union Pure & Appl Chem, Natl Inst Hlth, Switzerland, Swiss Natl Fdn, F Hoffmann La Roche Ltd, BASF Nederland B V, Betatene Ltd, Austr, Birkhauser Verlag, Switzerland, Bruker Nederland B V, Coca Cola Co, US, Kemin Ind, US, Wyeth Ayerst, US, European Community, Leiden City Council, Leiden Univ, Royal Dutch Acad Sci, Royal Dutch Chem Soc, Royal Gist Brocades N V, Netherlands, Dutch Soc Biochem & Molec Biol ID HUMAN PLASMA; MACULAR PIGMENT; CAROTENOIDS; SEPARATION; QUANTIFICATION; EXTRACTS; AGE AB Purpose. To characterize fully all the major and minor carotenoids and their metabolites in human retina and probe for the presence of the oxidative metabolites of lutein and zeaxanthin. Methods, Carotenoids of a composite of 58 pairs of human retinas and a monkey retina were elucidated by comparing their high-performance liquid chromatography (HPLC)-ultraviolet/visible absorption spectrophotometry (UV/Vis)-mass spectrometry (MS) profile with those of authentic standards prepared by organic synthesis. Results. In addition to lutein and zeaxanthin, several oxidation products of these compounds were present in the extracts from human retina. A major carotenoid resulting from direct oxidation of lutein was identified as 3-hydroxy-beta,epsilon-caroten-3'-one. Minor carotenoids were identified as: 3'-epilutein,epsilon ,epsilon-carotene-3,3'-diol, epsilon,epsilon-carotene-3,3'-dione, 3'-hydroxy-epsilon,epsilon-caroten-one, and 2,6-cyclolycopene-1,5-diol. Several of the geometric isomers of lutein and zeaxanthin were also detected at low concentrations. These were as follows: 9-cis-lutein, 9'-cis-lutein, 13-cis-lutein, 13'-cis-lutein, 9-cis-zeaxanthin, and 13-cis-zeaxanthin. Similar results were also obtained from HPLC analysis of a freshly dissected monkey retina. Conclusions. Lutein, zeaxanthin, 3'-epilutein, and 3-hydroxy-beta,epsilon-caroten-3'-one in human retina may be interconverted through a series of oxidation-reduction reactions similar to our earlier proposed metabolic transformation of these compounds in humans. The presence of the direct oxidation product of lutein and 3'-epilutein (metabolite of lutein and zeaxanthin) in human retina suggests that lutein and zeaxanthin may act as antioxidants to protect the macula against short-wavelength visible light. The proposed oxidative-reductive pathways for lutein and zeaxanthin in human retina, may therefore play an important role in prevention of age-related macular-degeneration and cataracts. C1 CATHOLIC UNIV AMER,DEPT CHEM,WASHINGTON,DC 20064. UNIV UTAH,HLTH SCI CTR,MORAN EYE CTR,SALT LAKE CITY,UT. NEI,LAB MECHANISMS OCULAR DIS,BETHESDA,MD 20892. RP Khachik, F (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,CAROTENOIDS RES UNIT,BLDG 161 E,BELTSVILLE,MD 20705, USA. RI Khachik, Frederick/C-5055-2009 NR 24 TC 268 Z9 283 U1 1 U2 16 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 1997 VL 38 IS 9 BP 1802 EP 1811 PG 10 WC Ophthalmology SC Ophthalmology GA XU430 UT WOS:A1997XU43000017 PM 9286269 ER PT J AU Zimmer, Z Myers, A AF Zimmer, Z Myers, A TI Receptivity to protective garments among the elderly SO JOURNAL OF AGING AND HEALTH LA English DT Article ID RISK-FACTORS; HIP-FRACTURES; INJURIOUS FALLS; COMMUNITY; PEOPLE; POPULATION; HEALTH; WOMEN AB Hip fractures among elders resulting from falls are a growing concern as the proportion of elders increases and health care costs mount. A recent innovation is the development of an undergarment worn to protect against hip injuries. This study attempted to determine whether a community population of elders would be receptive to wearing such a garment and the characteristics of those who would and would not be receptive. It was assumed that receptivity can be predicted by variables that have been shown to relate to risks of falling. Predictor characteristics represent three domains: demographic/predisposition, health/mobility, and social support. A logistic regression procedure was employed to determine the probability and odds of receptivity among elders given a profile of specific characteristics. Results were interpreted with reference to past research on risks of falling. C1 NIA,BETHESDA,MD 20892. RP Zimmer, Z (reprint author), UNIV MICHIGAN,CTR POPULAT STUDIES,1225 S UNIV AVE,ANN ARBOR,MI 48104, USA. NR 41 TC 5 Z9 5 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD AUG PY 1997 VL 9 IS 3 BP 355 EP 372 DI 10.1177/089826439700900305 PG 18 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA XQ023 UT WOS:A1997XQ02300005 PM 10182398 ER PT J AU Jacot, JL Glover, JP Robison, WG AF Jacot, JL Glover, JP Robison, WG TI Computer analysis of corneal innervation density using a novel double stain in rat corneal whole mounts SO JOURNAL OF ANATOMY LA English DT Article DE gold chloride; acetylcholinesterase; corneal nerves; morphometry ID REGENERATION; CAPSAICIN; NERVES; BIRTH AB Computerised morphometry and a double stain technique were utilised to examine the corneal nerves in whole mounts, This novel stain combines the nonspecific acetylcholinesterase (NsAchE) and gold chloride (AuCl) procedures to enhance staining contrast and facilitate computerised detection of corneal nerves, Fresh rat corneas were dissected, and the Descemet's membrane-endothelium complex was removed, Then the corneas were fixed in 4% paraformaldehyde with 50 mM Na-K phosphate buffer (pH 7.2) and 8% sucrose for 30 min, They were rinsed and stained singly with NsAchE or AuCl, or were double stained using NsAchE followed by AuCl. Between NsAchE and AuCl staining the corneas were stored frozen in OCT compound at -70 degrees C. Flat mounts of whole come as were photographed before and after the second staining. Measurable stromal innervation density (mean +/- S.D.) in age-matched corneas stained with AuCl (3.90 +/- 0.36 mm/mm(2)) was not significantly different from that of NsAchE stained corneas. However, double staining compared with NsAchE staining of the same corneas revealed a 48 +/- 27% increase in demonstrable innervation density of the subepithelial nerve plexus (7.95 +/- 0.86 mm/mm(2) vs 5.52 +/- 1.31 mm/mm(2), respectively) Improved visualisation of epithelial nerves and their fine ramifications (leashes) was also obtained by double staining. This novel combination of 2 procedures enhances the detection of corneal nerves for analysis by computerised morphometry and provides a more representative estimate of total corneal innervation density. RP Jacot, JL (reprint author), NEI,SECT PATHOPHYSIOL,NIH,BLDG 6,ROOM 316,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 11 Z9 12 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0021-8782 J9 J ANAT JI J. Anat. PD AUG PY 1997 VL 191 BP 191 EP 199 DI 10.1046/j.1469-7580.1997.19120191.x PN 2 PG 9 WC Anatomy & Morphology SC Anatomy & Morphology GA XX052 UT WOS:A1997XX05200003 PM 9306196 ER PT J AU Sobel, DO Fleisher, T Karounos, DG AF Sobel, DO Fleisher, T Karounos, DG TI Characterization of a human T cell line reactive to a 52 kDa islet protein SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT 13th Immunology of Diabetes Workshop CY MAY 25-28, 1994 CL MONTVILARGENNE, FRANCE DE T cell line; 52 kDa protein; islet; human; IDDM ID DEPENDENT DIABETES-MELLITUS; MYELIN BASIC-PROTEIN; HEAT-SHOCK PROTEIN; RECEPTOR USAGE; LYMPHOCYTE-T; NOD MICE; ANTIGEN; CLONES; AUTOANTIBODIES; PANCREAS AB A 52 kDa islet protein has recently been identified as the target of autoantibodies in the NOD mouse model of IDDM and humans with IDDM. However, the presence of T cell immunity against the 52 kDa islet protein in IDDM has not been reported. We report the establishment and characterization of a T cell line (19KW) that reacts to purified 52 kDa islet protein (purified p52) from a subject with IDDM. The purified p52 induced a proliferative response as measured by thymidine incorporation in the 19KW T cell line with a stimulating index of up to 48. The proliferative responses were greater with increasing doses of purified p52 (0.1, 0.5, 2.0, and 6.0 mu g/well). No reactivity was found to a liver fraction purified in the same manner as 52 kDa protein, BSA, ovalbumin, extracts of rat muscle, fibroblast, adrenal, or pituitary tissue and to a rat exocrine cell tumor. Irradiated PBMC were required as antigen presenting cells (APC) for 19KW reactivity to the purified p52. The addition of anti-HLA DR or anti-HLA DQ antibodies significantly decreased the islet antigen-induced proliferative response. The addition of antibodies to HLA DP and class I MHC had no effect. Flow cytometric analysis revealed that the majority of T cells expressed CD4 and CD45RO molecules. T cell receptors V beta 6 and V eta 5.1 were found on 30 and 14% of the CD3(+) (T cells) 19KW cells, respectively. In conclusion, a purified p52-reactive human T cell line predominantly consisting of TCR V beta 6(+) and V beta 5.1(+) cells has been established from a subject. with IDDM. Reactivity to the purified p52 is antigen dose-dependent, tissue specific, requires irradiated PBMC as antigen presenting cells, and is HLA DR- and HLA DO-restricted. T cell lines specifically reactive to p52 may be useful for investigating further the role of this antigen in the pathogenesis of IDDM. (C) 1997 Academic Press Limited. C1 GEORGETOWN UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20007. GEORGETOWN UNIV,SCH MED,LOMBARDI CANC CTR,WASHINGTON,DC 20007. NIH,SERV IMMUNOL,CP,CC,BETHESDA,MD 20892. UNIV KENTUCKY,COLL MED,DEPT MED,VET AFFAIRS MED CTR,MED SERV,LEXINGTON,KY 40536. NR 53 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD AUG PY 1997 VL 10 IS 4 BP 387 EP 394 DI 10.1006/jaut.1997.0151 PG 8 WC Immunology SC Immunology GA XP646 UT WOS:A1997XP64600008 PM 9237802 ER PT J AU Kostenis, E Degtyarev, MY Conklin, BR Wess, J AF Kostenis, E Degtyarev, MY Conklin, BR Wess, J TI The N-terminal extension of G alpha(q) is critical for constraining the selectivity of receptor coupling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN ALPHA-SUBUNITS; BETA-GAMMA; MUSCARINIC RECEPTOR; PHOSPHOLIPASE-C; PALMITOYLATION; CLONING; IDENTIFICATION; SPECIFICITY; EXPRESSION; MEMBRANE AB Characteristically, an individual member of the superfamily of G protein coupled receptors can interact only with a limited number of the many structurally closely related G protein heterotrimers that are expressed within a cell. Interestingly, the N termini of two G protein a subunits, G alpha(q) and G alpha(11), differ from those of other or subunits in that they display a unique, highly conserved six-amino acid extension, To test the hypothesis that this sequence element is critical for proper receptor recognition, we prepared a G alpha(q) deletion mutant (-6q) lacking these first six amino acids. The -6q construct (or wild type G alpha(q) as a control) was coexpressed (in COS-7 cells) with several different G(i/o)- or G(s)-coupled receptors, and ligand-induced increases in inositol phosphate production were determined as a measure of G protein activation. Whereas these receptors did not efficiently interact with wild type G alpha(q), most of them gained the ability to productively couple to -6q. Additional experiments indicated that the observed functional promiscuity of -6q is not due to overexpression (as compared with wild type G alpha q) or to a lack of palmitoylation. We conclude that the N-terminal extension characteristic for G alpha(q/11) proteins is critical. for constraining the receptor coupling selectivity of these subunits, indicative of a novel mechanism by which the fidelity of receptor-G protein interactions can be regulated. C1 NIDDK,NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,DEPT MED,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,DEPT PHARMACOL,SAN FRANCISCO,CA 94141. NR 42 TC 65 Z9 66 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 AUG 1 PY 1997 VL 272 IS 31 BP 19107 EP 19110 DI 10.1074/jbc.272.31.19107 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP063 UT WOS:A1997XP06300004 PM 9235898 ER PT J AU Foncea, R Andersson, M Ketterman, A Blakesley, V SapagHagar, M Sugden, PH LeRoith, D Lavandero, S AF Foncea, R Andersson, M Ketterman, A Blakesley, V SapagHagar, M Sugden, PH LeRoith, D Lavandero, S TI Insulin-like growth factor-I rapidly activates multiple signal transduction pathways in cultured rat cardiac myocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE-ACTIVITY; LEFT-VENTRICULAR HYPERTROPHY; PROTEIN-COUPLED RECEPTORS; MUSCLE CELL HYPERTROPHY; GENE-EXPRESSION; PHOSPHATIDYLINOSITOL 3'-KINASE; PARACRINE MECHANISM; PLASMA-MEMBRANE; ANGIOTENSIN-II; STIMULATE AB In response to insulin-like growth factor-I (IGF-I), neonatal rat cardiac myocytes exhibit a hypertrophic response, The elucidation of the IGF-I signal transduction system in these cells remains unknown, We show here that cardiac myocytes present a single class of high affinity receptors (12,446 +/- 3,669 binding sites/cell) with a dissociation constant of 0.36 +/- 0.10 nM. Two different beta-subunits of IGF-I receptor were detected, and their autophosphorylation was followed by increases in the phosphotyrosine content of extracellular signal-regulated kinases (ERKs), insulin receptor substrate 1, phospholipase C-gamma 1, and phosphatidylinositol 3-kinase. IGF-I transiently activates c-Raf in cultured neonatal cardiac myocytes, whereas A raf is activated much less than c-Raf, Two peaks of ERK activity (ERK1 and ERK2) were resolved in cardiac myocytes treated with IGF-I by fast protein liquid chromatography, both being stimulated by IGF-I (with EC50 values for the stimulation of ERK1 and ERK2 by IGF-I of 0.10 and 0.12 nM, respectively), Maximal activation of ERK2 (12-fold) and ERK1 (8.3-fold) activities was attained after a 5-min exposure to IGF-I. Maximal activation of p90 S6 kinase by IGF-I was achieved after 10 min, and then the activity decreased slowly, Interestingly, IGF-I stimulates incorporation of [H-3]phenylalanine (1.6-fold) without any effect on [H-3]thymidine incorporation. These data suggest that IGF-I activates multiple signal transduction pathways in cardiac myocytes some of which may be relevant to the hypertrophic response of the heart. C1 UNIV CHILE,FAC CIENCIAS QUIM & FARMACEUT,DEPT BIOQUIM & BIOL MOL,SANTIAGO,CHILE. NATL HEART & LUNG INST,IMPERIAL COLL,SCH MED,DIV CARDIAC MED,LONDON SW3 6LY,ENGLAND. NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. OI Lavandero, Sergio/0000-0003-4258-1483 FU Wellcome Trust NR 76 TC 155 Z9 159 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 AUG 1 PY 1997 VL 272 IS 31 BP 19115 EP 19124 DI 10.1074/jbc.272.31.19115 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP063 UT WOS:A1997XP06300006 PM 9235900 ER PT J AU Gulati, S Chen, ZQ Brody, LC Rosenblatt, DS Banerjee, R AF Gulati, S Chen, ZQ Brody, LC Rosenblatt, DS Banerjee, R TI Defects in auxiliary redox proteins lead to functional methionine synthase deficiency SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COBALAMIN; HETEROGENEITY; CBLG; BIOSYNTHESIS; SYNTHETASE; BINDING; CULTURE; SYSTEM; LIVER; CELLS AB Methionine synthase catalyzes a methyl transfer reaction from methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate and is dependent on methylcobalamin, a derivative of vitamin B-12, for activity, Due to the lability of the intermediate, cob(I) alamin, the activity of methionine synthase is additionally dependent on a redox activation system. In bacteria, two flavoproteins, NADPH-flavodoxin reductase and flavodoxin, shuttle electrons from NADPH to methionine synthase, Their mammalian counterparts are unknown, and a putative intrinsic thiol oxidase activity of the mammalian methionine synthase has been proposed to be involved, We demonstrate that the mammalian methionine synthase can be activated in an NADPH-dependent reaction and requires a minimum of two redox proteins, This model is consistent with our results from biochemical complementation studies between cblG and cblE cell lines and mutation detection analysis in cblG cell lines, These demonstrate that the cblG; cell line has defects affecting methionine synthase directly, whereas the cblE cell line has defects in the redox proteins, We have also identified a P1173L mutation in the activation domain of methionine synthase in the cblG cell line WG1505. C1 UNIV NEBRASKA,DEPT BIOCHEM,LINCOLN,NE 68588. MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT MED,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT PEDIAT,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,DEPT BIOL,MONTREAL,PQ H3A 1A1,CANADA. MCGILL UNIV,MRC,GENET GRP,MONTREAL,PQ H3A 1A1,CANADA. NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK45776] NR 29 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 AUG 1 PY 1997 VL 272 IS 31 BP 19171 EP 19175 DI 10.1074/jbc.272.31.19171 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP063 UT WOS:A1997XP06300013 PM 9235907 ER PT J AU Glasgow, WC Hui, RT Everhart, AL Jayawickreme, SP AngermanStewart, J Han, BB Eling, TE AF Glasgow, WC Hui, RT Everhart, AL Jayawickreme, SP AngermanStewart, J Han, BB Eling, TE TI The linoleic acid metabolite, (13S)-hydroxyperoxyoctadecadienoic acid, augments the epidermal growth factor receptor signaling pathway by attenuation of receptor dephosphorylation - Differential response in Syrian hamster embryo tumor suppressor phenotypes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; ARACHIDONIC-ACID; DNA-SYNTHESIS; MAP KINASE; MITOGENIC RESPONSE; EGF RECEPTOR; CELLS; CANCER; MODULATION; EXPRESSION AB In Syrian hamster embryo (SHE) fibroblasts, epidermal growth factor receptor (EGFR) tyrosine kinase activity regulates the metabolism of endogenous linoleic acid to (13S)-hydroperoxyoctadecadienoic acid (13S)-HPODE), (13S)-HPODE stimulates EGF-dependent mitogenesis in a SHE cell phenotype, which expresses tumor suppressor genes (supB(+)), but was not effective in a variant that does not express these suppressor genes (supB(-)). In the present study, we have investigated the potential effects of this lipid metabolite on the EGFR signaling pathways in these two SHE cell lines, Treatment of quiescent SHE cells with EGF produced a rapid, transient increase in the tyrosine phosphorylation of EGFR, Dependence on EGF concentration for EGFR tyrosine phosphorylation was similar in both SHE cell lines, but a more prolonged phosphorylation was detected in the supB(-) variant. Incubation of supB(+) cells with (13S)-HPODE and EGF increased EGFR autophosphorylation and tyrosine phosphorylation on several signaling proteins with Src homology-a domains including GTPase-activating protein, The lipid metabolite did not significantly alter EGF-dependent tyrosine phosphorylation in the supB(-) variant, Tyrosine phosphorylation of mitogen-activated protein (MAP) kinase was also measured, The addition of (13S)-HPODE increased the extent and duration of MAP kinase tyrosine phosphorylation in supB(+) cells but not in the supB(-) variant, MAP kinase activity in supB(+) cells, as measured in immunoprecipitates from cells after the addition of EGF, was increased by the presence of (13S)-HPODE. The addition of (1SS)-HPODE did not directly alter EGFR kinase activity or the internalization of the EGFR, However, the addition of (13S)-HPODE to supB(+) cells extended the tyrosine phosphorylation of the EGFR in response to EGF, The dephosphorylation of the EGFR was measured directly, and a slower rate was observed in the supB(-) compared with the supB(+) cells, Incubation of the supB(+) cells with (1SS)-HPODE attenuated the dephosphorylation of the EGFR. Thus, (13S)-HPODE stimulates EGF-dependent mitogenesis and up-regulation of EGF-dependent tyrosine phosphorylation by inhibiting the dephosphorylation of the EGFR. This study shows that a metabolite of an essential dietary fatty acid, linoleic acid, can modulate tyrosine phosphorylation and activity of key signal transduction proteins in a growth factor mitogenic pathway. C1 NIEHS,EICOSANOID BIOCHEM SECT,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. MERCER UNIV,SCH MED,DIV BASIC MED SCI,MACON,GA 31207. NR 39 TC 55 Z9 55 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 1 PY 1997 VL 272 IS 31 BP 19269 EP 19276 DI 10.1074/jbc.272.31.19269 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP063 UT WOS:A1997XP06300027 PM 9235921 ER PT J AU Lindley, PF Card, G Zaitseva, I Zaitsev, V Reinhammar, B SelinLindgren, E Yoshida, K AF Lindley, PF Card, G Zaitseva, I Zaitsev, V Reinhammar, B SelinLindgren, E Yoshida, K TI An X-ray structural study of human ceruloplasmin in relation to ferroxidase activity SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Article DE ceruloplasmin; ferroxidase; iron; metabolism; copper transport ID ASCORBATE OXIDASE; NONSENSE MUTATION; HUMAN SERUM; GENE; CENTERS; BINDING; PLASMA AB The role of ceruloplasmin as a ferroxidase in the blood, mediating the release of iron from cells and its subsequent incorporation into serum transferrin, has long been the subject of speculation and debate. However, a recent X-ray crystal structure determination of human ceruloplasmin at a resolution of around 3.0 Angstrom, in conjunction with studies associating mutations in the ceruloplasmin gene with systemic haemosiderosis in humans, has added considerable weight to the argument in favour of a ferroxidase role for this enzyme. Further X-ray studies have now been undertaken involving the binding of the cations Co(II), Fe(II), Fe(III), and Cu(II) to ceruloplasmin. These results give insights into a mechanism for ferroxidase activity in ceruloplasmin. The residues and sites involved in ferroxidation are similar to those proposed for the heavy chains of human ferritin. The nature of the ferroxidase activity of human ceruloplasmin is described in terms of its three-dimensional molecular structure. C1 SERC,DARESBURY LAB,CCLRC,WARRINGTON WA4 4AD,CHESHIRE,ENGLAND. UNIV LONDON BIRKBECK COLL,DEPT CRYSTALLOG,LONDON WC1E 7HX,ENGLAND. GOTHENBURG UNIV,LUNDBERG LAB,DEPT BIOCHEM & BIOPHYS,S-41390 GOTHENBURG,SWEDEN. CHALMERS UNIV TECHNOL,DEPT PHYS,S-41296 GOTHENBURG,SWEDEN. NIDR,GENE TARGETTING RES & CORE FACIL,NIH,BETHESDA,MD 20892. SHINSHU UNIV,SCH MED,DEPT MED NEUROL,MATSUMOTO,NAGANO 390,JAPAN. NR 24 TC 86 Z9 90 U1 1 U2 18 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0949-8257 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD AUG PY 1997 VL 2 IS 4 BP 454 EP 463 DI 10.1007/s007750050156 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA XU082 UT WOS:A1997XU08200006 ER PT J AU Lietman, SA Yanagishita, M Sampath, TK Reddi, AH AF Lietman, SA Yanagishita, M Sampath, TK Reddi, AH TI Stimulation of proteoglycan synthesis in explants of porcine articular cartilage by recombinant osteogenic protein-1 (bone morphogenetic protein-7) SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID GROWTH-FACTOR-BETA; HUMAN EMBRYONIC-DEVELOPMENT; CELLS; SUPERFAMILY; METABOLISM; CULTURES; DIFFERENTIATION; MEMBERS; MATRIX; OP-1 AB Osteogenic protein-1 (also known as bone morphogenetic protein-7) is a member of the bone morphogenetic protein family, Bone morphogenetic proteins and related members of the TGF-beta (transforming growth factor-beta) superfamily are involved in the development and repair of bone. Recombinant bone morphogenetic proteins induce the formation of new cartilage and bone at heterotopic sites, We investigated the influence of recombinant osteogenic protein-1 (at doses of three, ten, thirty, or 100 nanograms per milliliter) on the synthesis and release of proteoglycans and the maintenance of a steady-state concentration of proteoglycans in explants of porcine articular cartilage that were maintained in chemically defined serum-free medium. We found a dose-dependent stimulation of proteoglycan synthesis and a concurrent decrease in the rate of release of proteoglycans from the explants. The size of the proteoglycan monomers and the composition of the glycosaminoglycan chains in the untreated articular cartilage were similar to those in the articular cartilage treated with osteogenic protein-1, The capacity of the newly synthesized proteoglycan monomers to form aggregates with exogenous hyaluronic acid was found to be similar to that of proteoglycans in bovine nasal cartilage. Our results demonstrated that osteogenic protein-1 stimulated the synthesis of proteoglycans and diminished the release of proteoglycans front explants of porcine articular cartilage. CLINICAL RELEVANCE: The maintenance and repair of articular cartilage is a formidable challenge in clinical orthopaedics. The stimulation of proteoglycan synthesis by osteogenic protein-1 (bone morphogenetic protein-7) in explants of cartilage maintained in chemically defined serum-free medium implies that recombinant osteogenic protein-1 may play a role in the maintenance of a steady-state concentration of proteoglycans in articular cartilage, a desirable prerequisite for optimum repair of cartilage, Osteogenic protein-1 can initiate the formation of cartilage from mesenchymal cells, Once new cartilage has formed at the site of repair; osteogenic protein-1 also may maintain the synthesis of proteoglycans. C1 NIDR, NIH, BETHESDA, MD 20892 USA. CREAT BIOMOL, HOPKINTON, MA 01748 USA. RP Lietman, SA (reprint author), JOHNS HOPKINS UNIV, SCH MED, DEPT ORTHOPAED SURG, 720 RUTLAND AVE, ROSS 225, BALTIMORE, MD 21205 USA. NR 35 TC 47 Z9 54 U1 0 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 EI 1535-1386 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG PY 1997 VL 79A IS 8 BP 1132 EP 1137 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA XT056 UT WOS:A1997XT05600003 PM 9278071 ER PT J AU Heppner, C Agarwal, SK Kester, MB Olufemi, SE Green, JS Skarulis, MC Kim, YS Saggar, SK Guru, SC Manickam, P Lubensky, IA Zhuang, Z Chandrasekharappa, SC Collins, FS EmmertBuck, MR Liotta, LA Spiegel, AM Burns, AL Marx, SJ AF Heppner, C Agarwal, SK Kester, MB Olufemi, SE Green, JS Skarulis, MC Kim, YS Saggar, SK Guru, SC Manickam, P Lubensky, IA Zhuang, Z Chandrasekharappa, SC Collins, FS EmmertBuck, MR Liotta, LA Spiegel, AM Burns, AL Marx, SJ TI Genotype-phenotype analysis in kindreds with familial multiple endocrine neoplasia type 1 (MEN1) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDDKD,NIH,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. NATL HUMAN GENOME RES INST,NIH,BETHESDA,MD. HLTH SCI CTR,ST JOHNS,NF,CANADA. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP 18 EP 18 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700019 ER PT J AU Xing, L Schwartzberg, P Sawyer, T Varmus, HE Boyce, BF AF Xing, L Schwartzberg, P Sawyer, T Varmus, HE Boyce, BF TI Induction of osteoclast apoptosis by mutated src proteins and a src SH2 inhibitor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 PARKE DAVIS PHARMACEUT,ANN ARBOR,MI. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP 25 EP 25 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700025 ER PT J AU Hoffmann, O Schwartzberg, P Varmus, HE AF Hoffmann, O Schwartzberg, P Varmus, HE TI Cytoskeletal organization of osteoclasts from mutant Src transgenic mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV VIENNA,DEPT PHARMACOL & TOXICOL,VIENNA,AUSTRIA. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP 26 EP 26 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700027 ER PT J AU Xu, T Longneck, G Fisher, L Heegaard, AM Satomura, K Bianco, P Sommer, B Kulkarni, A Robey, PG Young, MF AF Xu, T Longneck, G Fisher, L Heegaard, AM Satomura, K Bianco, P Sommer, B Kulkarni, A Robey, PG Young, MF TI Mice with targeted disruption of the biglycan gene exhibit decreased bone density and increased expression of decorin. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. NIDR,GENE TARGETING RES & CORE FACIL,NIH,BETHESDA,MD 20892. UNIV AQUILA,I-67100 LAQUILA,ITALY. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP 92 EP 92 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700092 ER PT J AU Pan, LC Ke, HZ Simmons, HA Crawford, DT ChidseyFrink, KL McCurdy, SP Schafer, JR Kimbro, KS Taki, M Korach, KS Thompson, DD AF Pan, LC Ke, HZ Simmons, HA Crawford, DT ChidseyFrink, KL McCurdy, SP Schafer, JR Kimbro, KS Taki, M Korach, KS Thompson, DD TI Estrogen receptor-alpha knockout (ERKO) mice lose trabecular and cortical bone following ovariectomy. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 PFIZER INC,CENT RES,GROTON,CT 06340. NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 4 Z9 4 U1 0 U2 1 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 AUG PY 1997 VL 12 SU 1 BP 126 EP 126 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700127 ER PT J AU Dieudonne, SC Fedarko, NS Kuznetsov, SA Satomura, K Mankani, M Harris, SA Robey, PG Young, MF AF Dieudonne, SC Fedarko, NS Kuznetsov, SA Satomura, K Mankani, M Harris, SA Robey, PG Young, MF TI Rescue of estrogen response in human marrow stromal fibroblasts derived from a patient with a nonfunctional estrogen receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIH,CSDB,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP 129 EP 129 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700129 ER PT J AU Xing, L Franzoso, G Siebenlist, U Boyce, BF AF Xing, L Franzoso, G Siebenlist, U Boyce, BF TI Targeted disruption of the P50 and P52 subunits of NF-kappa B transcription factor leads to failure of osteoclast formation and osteopetrosis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP 133 EP 133 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700133 ER PT J AU Riminucci, M Shapiro, I Bianco, P Robey, PG AF Riminucci, M Shapiro, I Bianco, P Robey, PG TI Abnormal bone formation in McCune-Albright Syndrome is linked to apoptosis of misfunctioning osteoblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. UNIV AQUILA,I-67100 LAQUILA,ITALY. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP 160 EP 160 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700160 ER PT J AU Kiel, DP Zhang, Y Levy, D Wilson, PWF Cupples, LA Felson, DT AF Kiel, DP Zhang, Y Levy, D Wilson, PWF Cupples, LA Felson, DT TI Do women with higher bone mass have a lower risk of myocardial infarction SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,HEBREW REHABIL CTR AGED,BOSTON,MA 02131. BOSTON UNIV,ARTHRIT CTR,BOSTON,MA 02131. NHLBI,SCH MED,BOSTON,MA 02131. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,BOSTON,MA 02131. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP 171 EP 171 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700170 ER PT J AU Kiel, DP Kauppila, L Wilson, PWF Cupples, LA AF Kiel, DP Kauppila, L Wilson, PWF Cupples, LA TI Bone loss and the progression of lumbar aortic calcification SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA 02131. HARVARD UNIV,SCH MED,HEBREW REHABIL CTR AGED,BOSTON,MA 02131. NHLBI,BOSTON,MA 02131. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,BOSTON,MA 02131. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP 174 EP 174 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700175 ER PT J AU Stubbs, JT Mintz, KP Eanes, ED Torchia, DA Fisher, LW AF Stubbs, JT Mintz, KP Eanes, ED Torchia, DA Fisher, LW TI Characterization of native and recombinant bone sialoprotein: Delineation of the mineral-binding and cell adhesion domains and structural analysis of the RGD domain SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 09-13, 1995 CL BALTIMORE, MD SP Amer Soc Bone & Mineral Res ID MESSENGER-RNA EXPRESSION; MATRIX PROTEINS; CDNA CLONING; HYDROXYAPATITE; BSP; OSTEOBLASTS; FIBRONECTIN; OSTEOPONTIN; ATTACHMENT; INHIBITION AB Bone sialoprotein is a small, sulfated, and phosphorylated integrin-binding glycoprotein apparently found only in tissues that eventually mineralize, Nondenatured bone sialoprotein (BSP) purified from rat osteosarcoma cell line (UMR 106-01 BSP) culture media is shown to have a hydroxyapatite K-d approximate to 2.6 x 10(-9) M, perhaps the strongest affinity for this mineral of any of the matrix proteins, Both native BSP and a 47 kD fragment of UMR-BSP (Fragment 1 similar to 133A-similar to 265Y) are more potent inhibitors of seeded hydroxyapatite crystal growth than recombinant human BSP fragments lacking post-translational modifications, The recombinant proteins, however, do show reproducible inhibitory activity, suggesting that at least some of the strong mineral-binding properties are encoded directly within the protein sequence itself, BSP facilitates the adhesion of several cell types through its integrin binding (RGD) tripeptide sequence. Nuclear magnetic resonance (NMR) analysis of a N-15-enriched 59 amino acid recombinant domain containing the RGD tripeptide shows that the structure of this isolated domain is highly flexible with or without 5 mM calcium, Previous work has also shown that an endogenous fragment of UMR-BSP (Fragment 1) supports cell adhesion in the absence of the RGD sequence, In this report, non-ROD cell adhesion sites are localized within conserved amino- and carboxy-terminal tyrosine-rich domains of recombinant human BSP, Given the proximity of the latter non-RGD cell adhesion site to the RGD tripeptide, a model of BSP-receptor interactions is presented. C1 NIDR, CRANIOFACIAL & SKELETAL DIS BRANCH, NIH, BETHESDA, MD 20892 USA. UNIV VERMONT, COLL MED, BURLINGTON, VT USA. UNIV VERMONT, COLL AGR & LIFE SCI, DEPT MICROBIOL & MOL GENET, BURLINGTON, VT USA. NR 51 TC 78 Z9 82 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1997 VL 12 IS 8 BP 1210 EP 1222 DI 10.1359/jbmr.1997.12.8.1210 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XN797 UT WOS:A1997XN79700009 PM 9258751 ER PT J AU Glorieux, FH Bishop, NJ Travers, R Roughley, P Chabot, G Lanoue, G Fassier, F Glorieux, D Hopkins, E Marini, J AF Glorieux, FH Bishop, NJ Travers, R Roughley, P Chabot, G Lanoue, G Fassier, F Glorieux, D Hopkins, E Marini, J TI Type V osteogenesis imperfecta. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MCGILL UNIV,MONTREAL,PQ,CANADA. SHRINERS HOSP CRIPPLED CHILDREN,GENET UNIT,MONTREAL,PQ H3G 1A6,CANADA. NICHHD,BETHESDA,MD. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP F653 EP F653 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701141 ER PT J AU Hoang, BH Luyten, FP Ballock, RT AF Hoang, BH Luyten, FP Ballock, RT TI Expression of Frzb, a novel frizzled-related the developing rodent. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,RAINBOW BABIES & CHILDRENS HOSP,DEPT ORTHOPAED,CLEVELAND,OH 44106. NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP F344 EP F344 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700834 ER PT J AU Kuznetsov, SA Robey, PG AF Kuznetsov, SA Robey, PG TI Concentration of marrow colony forming units fibroblast (CFU-Fs) is significantly altered in skeletal disorders. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 3 Z9 3 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 AUG PY 1997 VL 12 SU 1 BP F440 EP F440 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700930 ER PT J AU Langlois, JA Pahor, M Bauer, D Havlik, R AF Langlois, JA Pahor, M Bauer, D Havlik, R TI Calcium channel blocker use and risk of hip fracture in old age. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. UNIV TENNESSEE,MEMPHIS,TN. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP F533 EP F533 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701021 ER PT J AU Lester, GE Cooper, GS Taylor, JA AF Lester, GE Cooper, GS Taylor, JA TI Vitamin D receptor polymorphisms, bone mineral density, and bone metabolism in perimenopausal women. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP F583 EP F583 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701072 ER PT J AU Riminucci, M Robey, PG Bianco, P AF Riminucci, M Robey, PG Bianco, P TI Gs alpha mutation leading to excess cAMP in McCune-Albrigbt syndrome (MAS) results in production of IL-6 by abnormal osteoblasts and an increase in bone resorption SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. UNIV AQUILA,I-67100 LAQUILA,ITALY. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP F656 EP F656 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701146 ER PT J AU Robey, PG Kuznetsov, SA Riminucci, M Majolagbe, A Bianco, P AF Robey, PG Kuznetsov, SA Riminucci, M Majolagbe, A Bianco, P TI Establishment of fibrous dysplasia of bone in McCune-Albright Syndrome may require both normal and mutated cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. UNIV AQUILA,I-67100 LAQUILA,ITALY. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP F655 EP F655 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701144 ER PT J AU Satomura, K IbarakiOConnor, K Kuznetsov, SA Young, MF Robey, PG AF Satomura, K IbarakiOConnor, K Kuznetsov, SA Young, MF Robey, PG TI Receptor tyrosine kinase expression in human bone marrow stromal fibroblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP F353 EP F353 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700841 ER PT J AU Tobin, JD Phang, LJ Roy, TA Harman, SM Blackman, MR Bellantoni, MF AF Tobin, JD Phang, LJ Roy, TA Harman, SM Blackman, MR Bellantoni, MF TI Longitudinal assessment of bone loss during the perimenopausal transition. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21201. JOHNS HOPKINS MED INST,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP F458 EP F458 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700947 ER PT J AU Kester, MB Agarwal, SK EmmertBuck, MR Debelenko, LV Guru, SC Manickam, P Olufemi, SE Kim, YS Heppner, C Saggar, SK Lubensky, IA Liotta, LA Chandrasekharappa, SC Collins, FS Spiegel, AM Burns, AL Marx, SJ AF Kester, MB Agarwal, SK EmmertBuck, MR Debelenko, LV Guru, SC Manickam, P Olufemi, SE Kim, YS Heppner, C Saggar, SK Lubensky, IA Liotta, LA Chandrasekharappa, SC Collins, FS Spiegel, AM Burns, AL Marx, SJ TI Haplotype analysis of 11q13 in 27 kindreds with familial multiple endocrine neoplasia type 1 (fMEN1) and mutation analysis of the MEN1 gene show founder effects SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDDKD,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NIH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP P318 EP P318 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700313 ER PT J AU Sekiya, I Koopman, P Watanabe, H Ezura, Y Yamada, Y Noda, M AF Sekiya, I Koopman, P Watanabe, H Ezura, Y Yamada, Y Noda, M TI SOX9 enhances aggrecan gene expression via the promoter region containing a single HMG-BOX-sequence in a chondrogenic cell line, TC6. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 TOKYO MED & DENT UNIV,MED RES INST,DEPT MOL PHARMACOL,TOKYO 101,JAPAN. NIDR,BETHESDA,MD 20892. UNIV QUEENSLAND,BRISBANE,QLD,AUSTRALIA. RI Ezura, Yoichi/L-9485-2016 NR 0 TC 6 Z9 6 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 AUG PY 1997 VL 12 SU 1 BP P222 EP P222 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700217 ER PT J AU Shih, K Lenherr, S Renyi, I Smith, CL Sackett, DL Barsony, J AF Shih, K Lenherr, S Renyi, I Smith, CL Sackett, DL Barsony, J TI Vitamin D receptor interactions with tubulin. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDDK,LAB CELL BIOCHEM & BIOL,BETHESDA,MD 20892. NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP P252 EP P252 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700246 ER PT J AU Agarwal, SK Guru, SC Kester, MB Burns, AL Kim, YS Olufemi, SE Crabtree, JS Wang, Y EmmertBuck, MR Debelenko, LV Weisemann, JM Heppner, C Manickam, P Saggar, SK Liotta, LA Roe, BA Boguski, MS Spiegel, AM Collins, FS Chandrasekharappa, SC Marx, SJ AF Agarwal, SK Guru, SC Kester, MB Burns, AL Kim, YS Olufemi, SE Crabtree, JS Wang, Y EmmertBuck, MR Debelenko, LV Weisemann, JM Heppner, C Manickam, P Saggar, SK Liotta, LA Roe, BA Boguski, MS Spiegel, AM Collins, FS Chandrasekharappa, SC Marx, SJ TI Mutational analysis of MEN1 candidate genes by dideoxy fingerprinting. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDDKD,NIH,BETHESDA,MD 20892. NIH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. UNIV OKLAHOMA,NORMAN,OK 73019. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP S660 EP S660 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701654 ER PT J AU Alexander, MB DeRubeis, AR Satomura, K Kuznetsov, SA Robey, PG AF Alexander, MB DeRubeis, AR Satomura, K Kuznetsov, SA Robey, PG TI Integrin subunit expression varies in different clonal strains of human marrow stromal fibroblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 1 U2 1 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 AUG PY 1997 VL 12 SU 1 BP S244 EP S244 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701239 ER PT J AU Bohannon, AD Cooper, GS Meier, DM Wolff, M AF Bohannon, AD Cooper, GS Meier, DM Wolff, M TI DDT [2,2-bis(p-chlorophenyl)-1,1,1trichloroethane] and bone mineral density. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC 27706. NIEHS,RES TRIANGLE PK,NC 27709. MT SINAI MED CTR,NEW YORK,NY 10029. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP S511 EP S511 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701505 ER PT J AU Forlino, A Cabral, WA Marini, JC AF Forlino, A Cabral, WA Marini, JC TI Expression, secretion, and matrix incorporation of mutant type I collagen synthesized by cultured OI osteoblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NICHHD,SECT CONNECT TISSUE DISORDERS,HDB,NIH,BETHESDA,MD 20892. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP S527 EP S527 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701690 ER PT J AU LethbridgeCejku, M Tobin, JD Roy, TA Plato, CC Hochberg, MC AF LethbridgeCejku, M Tobin, JD Roy, TA Plato, CC Hochberg, MC TI Hand osteoarthritis (OA) is associated with greater rates of radial bone loss: Data from the Baltimore longitudinal study of aging (BLSA). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP S649 EP S649 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701644 ER PT J AU Mankani, M Satomura, K Kuznetsov, S Krebsbach, P Taylor, R Robey, PG AF Mankani, M Satomura, K Kuznetsov, S Krebsbach, P Taylor, R Robey, PG TI Engraftment of marrow stromal fibroblasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV MICHIGAN,ANN ARBOR,MI 48109. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP S205 EP S205 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701201 ER PT J AU Taki, M Kimbro, KS Washburn, TF Kiyokawa, A Okada, F Fukuda, C Miyamoto, M Korach, KS AF Taki, M Kimbro, KS Washburn, TF Kiyokawa, A Okada, F Fukuda, C Miyamoto, M Korach, KS TI Effects of estrogen receptor destruction on femurs from male mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIEHS,RECEPTOR BIOL SECT,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. SANKYO CO LTD,PHARMACOL & MOL BIOL RES LABS,SHINAGAWA KU,TOKYO 140,JAPAN. NR 0 TC 4 Z9 4 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 AUG PY 1997 VL 12 SU 1 BP S430 EP S430 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701424 ER PT J AU vanLeeuwen, JPTM Derkx, P Fisher, LW Nigg, AL Bosman, FT BirkenhagerFrenkel, DH Houtsmuller, AB Pols, HAP AF vanLeeuwen, JPTM Derkx, P Fisher, LW Nigg, AL Bosman, FT BirkenhagerFrenkel, DH Houtsmuller, AB Pols, HAP TI Immunolocalisation and quantification of noncollagenous bone matrix proteins in adult human bone in combination with histomorphometry. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 ERASMUS UNIV ROTTERDAM,SCH MED,DEPT INTERNAL MED 3,NL-3000 DR ROTTERDAM,NETHERLANDS. ERASMUS UNIV ROTTERDAM,SCH MED,DEPT PATHOL,NL-3000 DR ROTTERDAM,NETHERLANDS. NIH,BONE RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP S298 EP S298 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701292 ER PT J AU Wu, XY Peters, J Gonzales, F Gimble, J AF Wu, XY Peters, J Gonzales, F Gimble, J TI Comparison of bone marrow stromal cell progenitor frequency between wild type and PPAR alpha deficient mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. OKLAHOMA MED RES FDN,OKLAHOMA CITY,OK 73104. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP S419 EP S419 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701414 ER PT J AU Young, MF Kerr, JM Xu, T Sommer, B Dieudonne, S Kuznetsov, SA Robey, PG AF Young, MF Kerr, JM Xu, T Sommer, B Dieudonne, S Kuznetsov, SA Robey, PG TI The use of differential display to characterize human marrow stromal fibroblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP S204 EP S204 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62701199 ER PT J AU Fuller, K Chambers, TJ Leonard, EJ AF Fuller, K Chambers, TJ Leonard, EJ TI The effect of macrophage stimulating protein on the behavior of osteoclasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV LONDON ST GEORGES HOSP,SCH MED,LONDON SW17 0RE,ENGLAND. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP T361 EP T361 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700355 ER PT J AU Grzesik, WJ Kuznetsov, SA Mankani, M Robey, PG Cheng, H Yamauchi, M AF Grzesik, WJ Kuznetsov, SA Mankani, M Robey, PG Cheng, H Yamauchi, M TI Normal human cementum-derived cells - An in vitro and in vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV N CAROLINA,DENT RES CTR,CHAPEL HILL,NC 27599. NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP T408 EP T408 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700402 ER PT J AU Harada, S Machwate, M Wesolowski, G Moalli, M LaRochelle, WJ Rodan, GA AF Harada, S Machwate, M Wesolowski, G Moalli, M LaRochelle, WJ Rodan, GA TI Expression of keratinocyte growth factor FGF7 and its receptor in osteoblastic cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MERCK RES LABS,W POINT,PA 19486. NIH,BETHESDA,MD 20892. UNIV MICHIGAN,ANN ARBOR,MI 48109. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP T423 EP T423 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700416 ER PT J AU Migliaccio, S Taranta, A Newbold, RR Toverud, S Korach, KS Faraggiana, T Bernardini, S Teti, A AF Migliaccio, S Taranta, A Newbold, RR Toverud, S Korach, KS Faraggiana, T Bernardini, S Teti, A TI Estrogens modulate osteoclastogenesis and bone resorption in vivo and in vitro. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV ROMA LA SAPIENZA,IDI,HISTOL GEN EMBRIOL INST,ROME,ITALY. UNIV ROMA LA SAPIENZA,IDI,DEPT EXPER MED,ROME,ITALY. UNIV AQUILA,DEPT EXPER MED,I-67100 LAQUILA,ITALY. NIEHS,LRDT,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH DENT,CHAPEL HILL,NC 27515. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP T471 EP T471 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700464 ER PT J AU Wakisaka, A Tanaka, H Barnes, J Liang, CT AF Wakisaka, A Tanaka, H Barnes, J Liang, CT TI Effect of IGF-I infused locally on femoral gene expression and bone remodeling activity in old rats. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 12 SU 1 BP T413 EP T413 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP627 UT WOS:A1997XP62700407 ER PT J AU Sueoka, E Sueoka, N Okabe, S Kozu, T Komori, A Ohta, T Suganuma, M Kim, SJ Lim, IK Fujiki, H AF Sueoka, E Sueoka, N Okabe, S Kozu, T Komori, A Ohta, T Suganuma, M Kim, SJ Lim, IK Fujiki, H TI Expression of the tumor necrosis factor alpha gene and early response genes by nodularin, a liver tumor promoter, in primary cultured rat hepatocytes SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE tumor necrosis factor-alpha; early-response genes; liver carcinogen; mRNA stabilization; protein phosphatase inhibitor ID MESSENGER-RNA DEGRADATION; OKADAIC ACID; PROTEIN PHOSPHATASE-1; DIFFERENTIAL REGULATION; MICROCYSTIN-LR; INHIBITOR; BETA; AP1 AB Nodularin is a new liver carcinogen possessing a potent tumor-promoting activity in rat liver, mediated through inhibition of protein phosphatases 1 and 2A, and a weak initiating activity. Since we previously reported evidence that nodularin up-regulated expression of the tumor necrosis factor alpha gene (TNF alpha) and early-response genes in rat liver after its i.p. administration, and since TNF alpha had tumor-promoting activity in vitro, it is possible that TNF alpha itself is involved in liver tumor promotion. We investigated whether hepatocytes themselves induce expression of the TNF alpha gene and early-response genes in primary cultured rat hepatocytes treated with nodularin. Like nodularin, microcystin-LR, which is another liver tumor promoter belonging to the okadaic acid class, strongly induced TNF alpha gene expression in rat hepatocytes, as well as TNF alpha release from those cells into the medium. On the other hand, 12-O-tetradecanoylphorbol-13-acetate, which has been reported to induce no tumor promotion in rat liver, induced no apparent expression of the TNF alpha gene in primary cultured rat hepatocytes. As for the expression of early-response genes, 1 mu M nodularin or microcystin-LR induced expression of the c-jun, jun B, jun D, c-fos, fos B and fra-1 genes in the hepatocytes, and the expression of these genes was prolonged up to 24 h, suggesting mRNA stabilization induced by inhibition of protein phosphatases 1 and 2A. This paper presents new evidence that the TNF alpha gene and early-response genes were expressed in hepatocytes treated with a liver tumor promoter. C1 SAITAMA CANC CTR,RES INST,INA,SAITAMA 362,JAPAN. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. AJOU UNIV,SCH MED,DEPT BIOCHEM,SUWON 442749,SOUTH KOREA. NR 33 TC 53 Z9 61 U1 1 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD AUG PY 1997 VL 123 IS 8 BP 413 EP 419 DI 10.1007/s004320050080 PG 7 WC Oncology SC Oncology GA XR357 UT WOS:A1997XR35700001 PM 9292703 ER PT J AU Jiang, H Movsesyan, V Fink, DW Fasler, M Whalin, M Katagiri, Y Monshipouri, M Dickens, G Lelkes, PI Guroff, G Lazarovici, P AF Jiang, H Movsesyan, V Fink, DW Fasler, M Whalin, M Katagiri, Y Monshipouri, M Dickens, G Lelkes, PI Guroff, G Lazarovici, P TI Expression of human p140(trk) receptors in p140(trk)-deficient, PC12/endothelial cells results in nerve growth factor-induced signal transduction and DNA synthesis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE nerve growth factor; fibroblast growth factor; K-252a; staurosporine; p140(trk); receptor; signal transduction; tyrosine kinase; transfection; overexpression; PC12/endothelial hybrid cells; DNA synthesis; proliferation; differentiation ID TRK TYROSINE KINASE; PC12 CELLS; NEURONAL DIFFERENTIATION; NEURITE OUTGROWTH; CELLULAR ACTIONS; NGF RESPONSES; PROTOONCOGENE; RESPONSIVENESS; BINDING; STAUROSPORINE AB Nerve growth factor (NGF) regulates proliferation, differentiation, and survival of sympathetic and sensory neurons through the tyrosine kinase activity of its receptor, p140(trk). These biological effects of NGF depend upon the signal-mediating function of pi 40(trk) substrates which are likely to differ from cell to cell. To define pi 40(trk) receptor substrates and the details of signalling by NGF in the hybrid cell PC12EN, we stably transfected cultures with a vector encoding a full-length human pi 40(trk) cDNA sequence. Two stably transfected clones, one expressing p140(trk) with higher affinity (PC12EN-trk3; K-d 57.4 pM, B-max 9.7 pmole/mg) and one expressing p140(trk) with a lower affinity (PC12 EN-trk1; K-d 392.4 pM, B-max 5.7 pmole/mg) were generated. Radioreceptor assays indicate that transfected p140(trk) receptors show slow NGF-dissociation kinetics, are resistant to trypsin or Triton X-100 treatment, are specific for NGF compared to other neurotrophins, and are internalized or downregulated as are native PC12 p140(trk) receptors. NGF stimulates p140(trk) tyrosine phosphorylation in a dose-(0.01-10 ng/ml) and time-(5-120 min) dependent manner, and tyrosine phosphorylation was inhibited by 200-1,000 nM K-252a. NGF-induced Erk stimulation for 60 min was assessed using myelin basic protein as a substrate. NGF treatment also led to an increased phosphorylation of p70(S6k), SNT, and phospholipase C gamma, demonstrating that the major NGF-stimulated signalling pathways found in other cells are activated in PC12EN-trk cells. Staurosporine (5-50 nM) rapidly and dBcAMP(1 mM) more slowly, but not NGF induced morphological differentiation in PC12EN-trk cells. Rather, NGF treatment in low-serum medium stimulated a 1.3- and 2.3-fold increase in DNA synthesis measured by [H-3]thymidine incorporation in PC12EN-trk1 and PC12EN-trk3, respectively. These data highlight the functionality of the transfected p140(trk) receptors and indicate that these transfected cells may serve as a novel cellular model facilitating the study of the mitogenic properties of NGF signalling and the transducing role of the p140(trk) receptor substrates. (C) 1997 Wiley-Liss, Inc. C1 NICHHD,GROWTH FACTORS SECT,NIH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,FAC MED,DEPT PHARMACOL,SCH PHARM,IL-91010 JERUSALEM,ISRAEL. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. UNIV WISCONSIN,CELL BIOL LAB,DEPT MED,MILWAUKEE,WI 53201. NR 49 TC 29 Z9 30 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD AUG 1 PY 1997 VL 66 IS 2 BP 229 EP 244 DI 10.1002/(SICI)1097-4644(19970801)66:2<229::AID-JCB10>3.0.CO;2-C PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XH840 UT WOS:A1997XH84000010 PM 9213224 ER PT J AU Yano, K Kohn, LD Saji, M Okuno, A Cutler, GB AF Yano, K Kohn, LD Saji, M Okuno, A Cutler, GB TI Phe(576) plays an important role in the secondary structure and intracellular signaling of the human luteinizing hormone chorionic gonadotropin receptor SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LIMITED PRECOCIOUS PUBERTY; CONSTITUTIVELY ACTIVATING MUTATION; THYROTROPIN TSH RECEPTOR; 3RD CYTOPLASMIC LOOP; ALPHA-1B-ADRENERGIC RECEPTOR; MISSENSE MUTATION; POINT MUTATION; GENE; PHOSPHOINOSITIDE; SUBSTITUTIONS AB Recent studies have identified multiple activating mutations in the sixth transmembrane domain of LH/chorionic gonadotropin receptor (LH-CGR) in patients with male-limited precocious puberty. Computer analysis suggested that these mutations had an effect on the secondary structure of the third cytoplasmic loop and sixth transmembrane domain, and that Phe(576) was a critical conformational bridging residue between these regions that might be important for receptor activity. We made four amino acid substitutions of the Phe(576) (F576I, F576G, F576Y, F576E) in the LH/CG receptor to analyze its functional role. Computer analysis of secondary structure predicted that the F576E mutant changed the secondary structure to a totally helical conformation in the region of the third intracellular and sixth transmembrane domain. In contrast, the F576G, F576I, and F576Y mutants were predicted to change the helical conformation in the legion to an extended conformation. In expression studies, mutations of Phe(576) produced functional changes in cAMP and inositol phosphate (IP) signaling, and human CG (hCG) binding. Mutations predicted to cause an extended conformation exhibited two functional patterns: first, constitutively activating in cAMP signaling without changes in IP signaling or hCG binding (F576I and F576G), and second, constitutively activating in cAMP signaling with decreased hCG-induced cAMP and IP signaling and with both higher affinity and lower capacity of hCG binding (F576Y). The mutation predicted to cause a totally helical conformation resulted in no cAMP response and a minimal IP response to hCG stimulation, with negligible hCG binding (F576E). These data suggest that the common change induced by the F576I, F576G, and F576Y mutations to an extended conformation on the third cytoplasmic loop and sixth transmembrane domain of the LH/CGR results in increased Gs coupling and activation of adenylyl cyclase, The F576Y mutation appears to have an additional effect, beyond a modification in receptor conformation, that lends to higher affinity and lower capacity of hCG binding, as well as altered Gq coupling and phospholipase C activation The F576E mutation has a distinct and different impact on receptor conformation, which leads to negligible hCG binding and minimal function; however, the F576E mutation may provide a clue to understanding the receptor mutations that result in loss of function and pseudohermaphroditism. We conclude that Phe(576) plays an important role in the human LH/CGR with respect to receptor conformation, Gs coupling, and cAMP signaling consistent with predictions from mutations associated with male-limited precocious puberty. C1 NIDDKD, CELL REGULAT SECT, METAB DIS BRANCH, NIH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, DEPT SURG, BALTIMORE, MD 21205 USA. RP Yano, K (reprint author), ASAHIKAWA MED COLL, DEPT PEDIAT, NISHIKAGURA 4-5-3-11, ASAHIKAWA, HOKKAIDO 078, JAPAN. NR 25 TC 8 Z9 9 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 AUG PY 1997 VL 82 IS 8 BP 2586 EP 2591 DI 10.1210/jc.82.8.2586 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP098 UT WOS:A1997XP09800035 PM 9253338 ER PT J AU Michelson, D Galliven, E Hill, L Demitrack, M Chrousos, G Gold, P AF Michelson, D Galliven, E Hill, L Demitrack, M Chrousos, G Gold, P TI Chronic imipramine is associated with diminished hypothalamic-pituitary-adrenal axis responsivity in healthy humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; TYROSINE-HYDROXYLASE; BIOCHEMICAL MANIFESTATIONS; THERAPEUTIC IMPLICATIONS; STIMULATION TEST; RAT-BRAIN; DEPRESSION; STRESS; NEUROBIOLOGY; RECOVERY AB The hypercortisolism of melancholic depression is thought to reflect hypothalamic hypersecretion of CRH and may be related to the hyperarousal associated with this syndrome. Although chronic administration of imipramine to experimental animals significantly decreases CRH messenger RNA levels in the paraventricular nucleus, it is generally thought that resolution of hypercortisolism following recovery from depression is related to the improvement in mood and decrease in anxiety that accompanies recovery rather than an intrinsic effect of imipramine. The present study was designed to explore whether chronic imipramine administration to healthy, nondepressed volunteers is associated with effects on hypothalamic-pituitary-adrenal (HPA) axis function. We studied basal and provocative measures of HPA axis function in 14 healthy volunteers before and after 6 weeks of imipramine treatment at therapeutic doses. Imipramine was associated with decreased responses in peak ACTH and cortisol to ovine CRH and in peak ACTH to arginine vasopressin (P = 0.02, P = 0.003, and P = 0.02, respectively) without changes in indices of basal HPA axis function. These data are consistent with preclinical findings and support the hypothesis that imipramine has an intrinsic effect on central components of HPA axis function, potentially related to its therapeutic effects. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RI Demitrack, Mark/I-7697-2013 NR 28 TC 62 Z9 65 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1997 VL 82 IS 8 BP 2601 EP 2606 DI 10.1210/jc.82.8.2601 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP098 UT WOS:A1997XP09800038 PM 9253341 ER PT J AU DeLuca, F Ray, K Mancilla, EE Fan, GF Winer, KK Gore, P Spiegel, AM Baron, J AF DeLuca, F Ray, K Mancilla, EE Fan, GF Winer, KK Gore, P Spiegel, AM Baron, J TI Sporadic hypoparathyroidism caused by de novo gain-of-function mutations of the Ca2+-sensing receptor SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the Society-for-Pediatric-Research CY MAY 02-10, 1996 CL WASHINGTON, D.C. SP Soc Pediat Res ID FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; MOLECULAR-CLONING; SENSING RECEPTOR; GENE; LOCALIZATION; EXPRESSION; KIDNEY; CELLS; MODEL AB Activating mutations of the Ca2+-sensing receptor (CaR) gene have been identified in families with autosomal dominant hypoparathyroidism and in one patient with sporadic hypoparathyroidism. Here, we describe two additional patients with sporadic hypoparathyroidism. One patient presented with mild symptoms at age 18 yr, the other was severely symptomatic from infancy. A heterozygous missense mutation was identified in each patient. One mutation (L773R) involved the fifth transmembrane domain of the CaR, the other (N118K) affected the amino-terminal, extracellular domain. In both cases, the probands' parents lacked the mutation, indicating that the mutations arose de novo. In expression studies the mutations shifted the concentration-response curve to the left and increased maximal activity. We conclude that 1) sporadic hypoparathyroidism can be caused by de novo gain-of-function mutations of the CaR; 2) the phenotype can vary from mild to life-threatening hypocalcemia; 3) gain-of-function mutations can involve not only extracellular regions, as previously reported, but also transmembrane domains of the CaR; and 4) the mechanism of activation can involve both increased receptor sensitivity to Ca2+ and increased maximal signal transduction. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIDDK, METAB DIS BRANCH, BETHESDA, MD 20892 USA. NR 31 TC 73 Z9 76 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1997 VL 82 IS 8 BP 2710 EP 2715 DI 10.1210/jc.82.8.2710 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP098 UT WOS:A1997XP09800056 PM 9253358 ER PT J AU Cizza, G Lotsikas, AJ Licinio, J Gold, PW Chrousos, G AF Cizza, G Lotsikas, AJ Licinio, J Gold, PW Chrousos, G TI Plasma leptin levels do not change in patients with Cushing's disease shortly after correction of hypercortisolism - Comment SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID OBESE GENE; NEUROPEPTIDE-Y; EXPRESSION; STRESS; SYSTEM; RATS AB In the present study, we characterized the changes in plasma leptin levels in patients with pituitary Cushing's disease and in age- and sex-matched controls. Plasma levels of ACTH, cortisol, and leptin were measured before and after iv administration of ovine CRH in controls once and in patients twice (while they had active hypercortisolism and 10 days after successful surgery). Cushing's patients had elevated body mass indexes (34 +/- 1.9 vs. 22.9 +/- 0.8) and plasma leptin levels (35.6 +/- 3.4 vs. 9.2 +/- 1.9 ng/mL) compared to controls, which remained unchanged 10 days after successful transsphenoidal surgery and directly proportional to the body mass index. Plasma leptin levels were not affected by CRH infusion in either the controls or the patients despite clear-cut elevations in plasma ACTH and cortisol. These findings suggest that although acute changes in plasma cortisol do not affect plasma leptin, chronic hypercortisolism results in elevated leptin levels, probably by causing visceral obesity. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 20 TC 55 Z9 56 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1997 VL 82 IS 8 BP 2747 EP 2750 DI 10.1210/jc.82.8.2747 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP098 UT WOS:A1997XP09800062 PM 9253364 ER PT J AU Borkowski, TA Letterio, JJ Mackall, CL Saitoh, A Wang, XJ Roop, DR Gress, RE Udey, MC AF Borkowski, TA Letterio, JJ Mackall, CL Saitoh, A Wang, XJ Roop, DR Gress, RE Udey, MC TI A role for TGF beta 1 in Langerhans cell biology - Further characterization of the epidermal Langerhans cell defect in TGF beta 1 null mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE Langerhans cell; dendritic cell; transforming growth factor beta 1; growth factor; ontogeny ID COLONY-STIMULATING FACTOR; GROWTH-FACTOR-BETA; DENDRITIC CELLS; TARGETED DISRUPTION; II RECEPTORS; MACROPHAGE; EXPRESSION; MOUSE; SKIN; ANTIGEN AB Previous studies of TGF beta 1 null (-/-) mice indicated that the epidermis was devoid of Langerhans cells (LC) and that the LC deficiency was not secondary to the inflammation that is the dominant feature of the -/- phenotype (Borkowski, T.A., J.J. Letterio, A.G. Farr, and M.C. Udey. 1996. J. Exp. Med. 184:2417-2422). Herein, we demonstrate that dendritic cells could be expanded from the bone marrow of -/- mice and littermate controls. Bone marrow from -/- mice also gave rise to LC after transfer into lethally irradiated recipients. Thus, the LC defect in TGF beta 1 null mice does not result from an absolute deficiency in bone marrow precursors, and paracrine TGF beta 1 production is sufficient for LC development. Several approaches were used to assess the suitability of -/- skin for LC localization. A survey revealed that although a number of cytokine mRNAs were expressed de novo, mRNAs encoding proinflammatory cytokines known to mobilize LC from epidermis (IL-1 and TNF alpha) were not strikingly overrepresented in -/- skin. In addition, bone marrow-derived LC populated full-thickness TGF beta 1 null skin after engraftment onto BALB/c nu/nu recipients, Finally, the skin of transgenic mice expressing a truncated loricrin promoter-driven dominant-negative TGF beta type II receptor contained normal numbers of LC. Because TGF beta 1 signaling in these mice is disrupted only in keratinocytes and the keratinocyte hyperproliferative component of the TGF beta 1 -/- phenotype is reproduced, these results strongly suggest that the LC defect in TGF beta 1 null mice is not due to an epidermal abnormality but reflects a requirement of murine LC (or their precursors) for TGF beta 1. C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT DERMATOL,HOUSTON,TX 77030. FU NCI NIH HHS [CA52607] NR 41 TC 95 Z9 95 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 1 PY 1997 VL 100 IS 3 BP 575 EP 581 DI 10.1172/JCI119567 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XQ280 UT WOS:A1997XQ28000012 PM 9239404 ER PT J AU Bilato, C Curto, KA Monticone, RE Pauly, RR White, AJ Crow, MT AF Bilato, C Curto, KA Monticone, RE Pauly, RR White, AJ Crow, MT TI Inhibition of vascular smooth muscle cell migration by peptide and antibody antagonists of the alpha(v)beta(3) integrin complex is reversed by activated calcium/calmodulin-dependent protein kinase II SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cell migration; vascular smooth muscle cells; integrins; calcium; calcium/calmodulin-dependent protein kinase II ID GROWTH-FACTOR; ALPHA-V-BETA-3 INTEGRIN; EXTRACELLULAR-MATRIX; NEOINTIMA FORMATION; ENDOTHELIAL-CELLS; GENE-EXPRESSION; MELANOMA-CELLS; ADHESION; COLLAGEN; FIBRONECTIN AB The migration of vascular smooth muscle cells (VSMCs) is thought to play a key role In the pathogenesis of many vascular diseases and is regulated by soluble growth factors/ chemoattractants as well as interactions with the extracellular matrix. We have studied the effects of antibodies to rat beta 3 and human alpha(v) beta(3) integrins on the migration of VSMCs. Both integrin antibodies as well as cyclic RGD peptides that bind to the vitronectin receptors alpha(v) beta(3) and alpha(v) beta(5) significantly inhibited PDGF-directed migration. This resulted in a reduction in the accumulation of inositol (1,4,5) trisphosphate and the activation of calcium/calmodulin-dependent protein kinase II (CamKII), an important regulatory event in VSMC migration identified previously. PDGF-directed VSMC migration in the presence of the anti-integrin antibodies and cyclic RGD peptides was restored when intracellular CamKII activity was elevated by either raising intracellular calcium levels with the ionophore, ionomycin, or infecting with a replication-defective recombinant adenovirus expressing a constitutively activated CamKII cDNA (AdCMV.CKIID3). Rescue of rat VSMCs was also observed in stably transfected cell lines expressing constitutively activated but not wild-type CamKII, These observations identify a key intermediate in the regulation of VSMC migration by outside-in signaling from the integrin alpha(v) beta(3). C1 NIA,CARDIOVASC SCI LAB,CTR GERONTOL RES,VASC BIOL UNIT,NIH,BALTIMORE,MD 21224. NR 69 TC 76 Z9 80 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 1 PY 1997 VL 100 IS 3 BP 693 EP 704 DI 10.1172/JCI119582 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XQ280 UT WOS:A1997XQ28000027 PM 9239418 ER PT J AU Engler, HD Preuss, J AF Engler, HD Preuss, J TI Laboratory diagnosis of respiratory virus infections in 24 hours by utilizing shell vial cultures SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CLINICAL SPECIMENS; SYNCYTIAL VIRUS; RAPID DETECTION AB Immunofluorescence staining of centrifugation-enhanced shell vial (SV) cultures for respiratory viruses (RV) after 24 h of incubation, rather than the more commonly prescribed times of 48 h and 5 days, allowed for the detection of 77% of the RV-positive specimens that would ordinarily not have been detected as positive until 48 h. Staining SVs at 24 h also permitted earlier detection of viruses that were missed by rapid antigen detection methods. RP Engler, HD (reprint author), NIH,MICROBIOL SERV,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 8 TC 21 Z9 22 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 AUG PY 1997 VL 35 IS 8 BP 2165 EP 2167 PG 3 WC Microbiology SC Microbiology GA XL745 UT WOS:A1997XL74500052 PM 9230407 ER PT J AU Pazdur, R DiazCanton, E Ballard, WP Bradof, JE Graham, S Arbuck, SG Abbruzzese, JL Winn, R AF Pazdur, R DiazCanton, E Ballard, WP Bradof, JE Graham, S Arbuck, SG Abbruzzese, JL Winn, R TI Phase II trial of 9-aminocamptothecin administered as a 72-hour continuous infusion in metastatic colorectal carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOPOISOMERASE-I; CANCER-CHEMOTHERAPY; CAMPTOTHECIN; XENOGRAFTS; TUMORS; CPT-11; INVIVO AB Purpose: The camptothecin derivative irinotecan has demonstrated clinical activity in metastatic colorectal carcinoma in both chemotherapy-naive and fluorouracil-refractory patients. 9-Aminocamptothecin (9-AC; NSC 603071), another camptothecin derivative, wets selected for clinical development based on preclinical activity, including cures in human tumor xenografts resistant to standard anticancer agents, We report a phase II trial of 9-AC in patients with previously untreated metastatic colorectal carcinoma. Patients and Methods: Colorectal cancer patients with measurable disease, a performance status of 0 to 2 (Zubrod), and no prior chemotherapy for metastatic disease received 9-AC, A cycle of therapy was 35 mu g/m(2)/h for 72 consecutive hours (840 mu g/m(2)/d for 3 days) and rest on days 4 to 14; a course of therapy was defined as two cycles (28 days), Patients were assessed for response after two courses. Results: Seventeen patients with metastatic colorectal cancer were entered onto this trial, No complete or partial responses were noted, Treatment was well tolerated; toxic effects consisted mainly of neutropenia, nausea, vomiting, stomatitis, fatigue, and anemia, Grade 3 to 4 toxicity was limited to neutropenia (grade 3 in four patients and grade 4 in six), anemia (grade 3 in two patients), and vomiting (grade 3 in two patients). No grade 3 or 4 diarrhea occurred. Only two patients had their 9-AC dose reduced to 30 mu g/m(2)/h, The median nadir absolute granulocyte count (AGC) was 1,500/mu l. The median number of courses given was two and the median time to disease progression was 8 weeks, Conclusion: At the dose and schedule used in this trial, 9-AC lacked antitumor activity in metastatic colorectal cancer, 9-AC infusion schedules of longer duration are currently being investigated in this disease. (C) 1997 by American Society of Clinical Oncology. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CLIN INVEST,SECT COMMUNITY ONCOL,HOUSTON,TX 77030. ATLANTA REG COMMUNITY ONCOL PROGRAM,ATLANTA,GA. SPARTANBURG COMMUNITY ONCOL PROGRAM,SPARTANBURG,SC. NCI,DIV CANC TREATMENT DIAG & CTR,BETHESDA,MD 20892. RP Pazdur, R (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT GASTROINTESTINAL MED ONCOL & DIGEST DIS,DIV MED,BOX 92,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CA45809, CA16672] NR 27 TC 33 Z9 34 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 AUG PY 1997 VL 15 IS 8 BP 2905 EP 2909 PG 5 WC Oncology SC Oncology GA XN954 UT WOS:A1997XN95400018 PM 9256134 ER PT J AU Philibert, RA Richards, L Lynch, CF Winokur, G AF Philibert, RA Richards, L Lynch, CF Winokur, G TI The effect of gender and age at onset of depression on mortality SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 147th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 1994 CL PHILADELPHIA, PA SP Amer Psychiat Assoc, NIMH, Dept Vet Affairs, Cooperat Studies Program, Med Res Serv ID PREVALENCE; DISORDERS; DISEASE; ADULTS; RISK AB Background: Depression has a marked negative impact on geriatric patient mortality and morbidity. The risk factors and exact reasons for these effects are not well understood. Method: Seeking to better define the factors, we retrospectively analyzed the effects of gender and age at onset of affective disorder in a naturalistic study of 192 geriatric patients consecutively admitted to a large midwestern tertiary care center between 1980 and 1987 for the treatment of unipolar depression. Results: After controlling for age at index admission, patients with an onset of depression before age 40 suffered significantly (p < .05) less mortality in follow-up than those with onset after age 40. When effects of gender are examined, the effects of age at onset are most profound in women, with a threefold increase in the rate of death in the cohort with age at onset of depression after 70 years when compared to those with onset before age 40. Conclusion: These results and those of others suggest that depressed elderly women with no previous history of affective disorder are at a markedly increased risk compared with elderly women with a history of affective illness for morbidity and mortality and that a significant proportion of elderly depressed patients are admitted to a psychiatric hospital for a depression that is secondary to serious medical illness. C1 UNIV IOWA,COLL MED,DEPT PSYCHIAT,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT PATHOL,IOWA CITY,IA 52242. RP Philibert, RA (reprint author), NIMH,CLIN NEUROSCI BRANCH,49 CONVENT RD MSC 4405,BLDG 49,ROOM B1EE16,BETHESDA,MD 20892, USA. FU NIMH NIH HHS [T32 MH14620] NR 21 TC 21 Z9 21 U1 1 U2 2 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 AUG PY 1997 VL 58 IS 8 BP 355 EP 360 DI 10.4088/JCP.v58n0805 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA XT926 UT WOS:A1997XT92600005 PM 9515974 ER PT J AU HoffmanGoetz, L Gerlach, KK Marino, C Mills, SL AF HoffmanGoetz, L Gerlach, KK Marino, C Mills, SL TI Cancer coverage and tobacco advertising in African-American women's popular magazines SO JOURNAL OF COMMUNITY HEALTH LA English DT Article ID SMOKING; HEALTH; HAZARDS; MEDIA AB Mass circulating magazines offer an opportunity to inform large segments of the population about preventive health behaviors relevant for cancer control. We collected information about the number and type of cancer articles from January 1987 through December 1994 in Jet, Ebony and Essence magazines. These magazines each have a principal readership of African-American women and a paid circulation of 1,000,000 or more annually. Cancer articles were counted if the content was gender neutral or specifically targeted for women. There were 84 articles on cancer including 6 on lung cancer and 3 on other tobacco-related cancers. Nine additional references to lung cancer were mentioned under the general cancer category, but lung cancer was not the primary focus of the articles. There were 24 articles on breast cancer and 9 on cervical cancer over the 8 year period. Most of the articles (>70%) were short fillers of less than one page in length. A prevention focus was included in 42.2%, 75.0%, and 71.0% of the cancer articles in Jet, Ebony, and Essence respectively. Of the 649 health articles, 116 were on cardiovascular disease. In contrast, there were 1,477 tobacco advertisements over the 8 years. The number of cancer articles was not significantly associated with the number of tobacco advertisements. Because tobacco-related cancers are entirely preventable and contribute to the significant cancer burden, the lack of coverage of tobacco-related cancers is a missed opportunity for health promotion among African-American females. C1 NCI,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892. UNIV WATERLOO,WATERLOO,ON N2L 3G1,CANADA. NR 28 TC 28 Z9 28 U1 0 U2 2 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0094-5145 J9 J COMMUN HEALTH JI J. Community Health PD AUG PY 1997 VL 22 IS 4 BP 261 EP 270 DI 10.1023/A:1025100419474 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XL319 UT WOS:A1997XL31900004 PM 9247849 ER PT J AU Soon, LLL Ausio, J Breed, WG Power, JHT Muller, S AF Soon, LLL Ausio, J Breed, WG Power, JHT Muller, S TI Isolation of histones and related chromatin structures from spermatozoa nuclei of a dasyurid marsupial, Sminthopsis crassicaudata SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article ID HUMAN-SPERM CHROMATIN; MOUSE SPERMIOGENESIS; BASIC-PROTEINS; CORE HISTONES; PROTAMINES; EVOLUTION; DNA; ORGANIZATION; INVOLVEMENT; ANTIBODIES AB The spermatozoa of a dasyurid marsupial, Sminthopsis crassicaudata, have two distinct nuclear regions: uniformly electron-dense chromatin (C1) in the interior and fissured chromatin (C2) at the periphery. To investigate whether the differences in morphology are due to incorporation of different packaging proteins, spermatozoa nuclear proteins were characterised by acetic acid-urea polyacrylamide gel electrophoresis (PAGE) and fractionated by reverse-phase high-pressure liquid chromatography (HPLC). The main protein component was protamine I, but a complete histone complement (H1, H2A, H2B, H3, and H4) was also detected. Immunocytochemistry showed localisation of H4, H2B, and H2A histones to the periphery of the nuclei, a region that corresponded to the C2 chromatin. The fissures in the chromatin of this region disappeared following incubation with fish protamines, indicating that the nucleohistone C2 region may be incompletely condensed relative to nucleoprotamines. This observation is consistent with the view that 60% of phosphodiester charges remain negative in nucleohistone DNA, whereas all DNA charges are neutralised in highly compact nucleoprotamines. Treatment of spermatozoa with micrococcal nuclease showed that the C1 chromatin was resistant to digestion, whereas the C2 region was cleaved into 30- to 38-nm agglomerates and 11-nm nucleosomal-size structures. Thus, this study demonstrates that spermatozoa nuclei of this marsupial species contain peripherally localised histones, and the nucleohistone chromatin accounts for the different morphology of the C2 region compared with the rest of the nucleus. (C) 1997 Wiley-Liss, Inc. C1 UNIV ADELAIDE,DEPT ANAT SCI,ADELAIDE,SA 5005,AUSTRALIA. UNIV VICTORIA,DEPT BIOCHEM & MICROBIOL,VICTORIA,BC V8W 3P6,CANADA. FLINDERS UNIV S AUSTRALIA,DEPT HUMAN PHYSIOL,BEDFORD PK,SA 5042,AUSTRALIA. CNRS,INST BIOL MOL & CELLULAIRE,UPR 9021,F-67084 STRASBOURG,FRANCE. NCI,BIOL LAB,BETHESDA,MD 20892. RI Muller, Sylviane/J-5319-2014 NR 45 TC 17 Z9 17 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 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD AUG 1 PY 1997 VL 278 IS 5 BP 322 EP 332 PG 11 WC Zoology SC Zoology GA XG944 UT WOS:A1997XG94400006 PM 9216075 ER PT J AU Drayna, DT AF Drayna, DT TI Genetic linkage studies of stuttering: Ready for prime time? SO JOURNAL OF FLUENCY DISORDERS LA English DT Editorial Material ID SUSCEPTIBILITY; CONCORDANCE; CLONING; DISEASE RP NHGRI, GENOME TECHNOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 21 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0094-730X EI 1873-801X J9 J FLUENCY DISORD JI J. Fluency Disord. PD AUG PY 1997 VL 22 IS 3 BP 237 EP 240 DI 10.1016/S0094-730X(97)00010-7 PG 4 WC Audiology & Speech-Language Pathology; Education, Special; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Education & Educational Research; Linguistics; Rehabilitation GA YJ720 UT WOS:A1997YJ72000005 ER PT J AU Ge, P Kirk, KL AF Ge, P Kirk, KL TI Synthesis of 2-fluorotetronic acid SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article DE 2-fluorotetronic acid ID KETO-GAMMA-BUTYROLACTONES; FLUORINATION AB Fluorination of 2-bromotetronic acid (7) in ethanol produces 2-bromo-3-ethoxy-2-fluoro-gamma-butyrolactone (8). Tributyltin hydride reduction of 8 gives 2-fluorotetronic acid in good yield. C1 NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NR 12 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD AUG PY 1997 VL 84 IS 1 BP 45 EP 47 DI 10.1016/S0022-1139(97)00028-6 PG 3 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA XX700 UT WOS:A1997XX70000009 ER PT J AU Johnson, BD Zheng, W Korach, KS Scheuer, T Catterall, WA Rubanyi, GM AF Johnson, BD Zheng, W Korach, KS Scheuer, T Catterall, WA Rubanyi, GM TI Increased expression of the cardiac L-type calcium channel in estrogen receptor-deficient mice SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE heart; ion channels; action potential; electrocardiogram ID 17-BETA-ESTRADIOL; GENE; DISRUPTION; MECHANISM; ESTRADIOL; DISEASE; MOUSE; RISK AB Steroid hormones control the expression of many cellular regulators, and a role for estrogen in cardiovascular function and disease has been well documented. To address whether the activity of the L-type Ca2+ channel, a critical element in cardiac excitability and contractility, is altered by estrogen and its nuclear receptor, we examined cardiac myocytes from male mice in which the estrogen receptor gene had been disrupted (ERKO mice). Binding of dihydropyridine Ca2+ channel antagonist isradipine (PN200-110) was increased 45.6% in cardiac membranes from the ERKO mice compared to controls, suggesting that a lack of estrogen receptors in the heart increased the number of Ca2+ channels. Whole-cell patch clamp of acutely dissociated adult cardiac ventricular myocytes indicated that Ca2+ channel current was increased by 49% and action potential duration was increased by 75%. Examination of electrocardiogram parameters in ERKO mice showed a 70% increase in the QT interval without significant changes in PQ or QRS intervals. These results show that the membrane density of the cardiac L-type Ca2+ channel is regulated by the estrogen receptor and suggest that decreased estrogen may lead to an increase in the number of cardiac L-type Ca2+ channels, abnormalities in cardiac excitability, and increased risk of arrhythmia and cardiovascular disease. C1 UNIV WASHINGTON,DEPT PHARMACOL,SEATTLE,WA 98195. BERLEX BIOSCI,RICHMOND,CA 94804. NIEHS,RECEPTOR BIOL SECT,RES TRIANGLE PK,NC 27709. RI Zheng, Wei/J-8889-2014; OI Zheng, Wei/0000-0003-1034-0757; Korach, Kenneth/0000-0002-7765-418X FU NHLBI NIH HHS [P01 HL044948, P01 HL44948] NR 32 TC 112 Z9 116 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 1997 VL 110 IS 2 BP 135 EP 140 DI 10.1085/jgp.110.2.135 PG 6 WC Physiology SC Physiology GA XP999 UT WOS:A1997XP99900005 PM 9236206 ER PT J AU Fulwood, R AF Fulwood, R TI Setting the agenda for research and education on coronary heart disease SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Editorial Material CT Conference on Issues of the Heart: Prevention, Management and Control of Cardiovascular Risk Factors in African Americans CY OCT 04-05, 1996 CL MEHARRY MED COLL, NASHVILLE, TN SP Natl Heart Lung & Blood Inst HO MEHARRY MED COLL DE African Americans; coronary heart disease; pulmonary disease; community outreach; high blood pressure; high blood cholesterol; obesity AB Coronary heart disease (CHD) disproportionately affects the African American population with death and disability. The disparity in mortality continues to exist between the general population and African Americans despite decreases in death rates in both groups since the 1970s. The National Heart, Lung, and Blood Institute (NHLBI) is committed to developing and supporting research and activities that improve the health of African Americans through community partnership initiatives. One such initiative is the CHD in Blacks Project, developed to increase awareness of the adverse effects of CHD, encourage healthy lifestyle behaviors, and, among health professionals, ensure that the latest treatment guidelines from the NHLBI in high blood pressure, high blood cholesterol, and obesity are used. The NHLBI has also established a network of health professionals from across the country to assist in developing medical education programs and community education outreach activities in conjunction with the National Medical Association, the Association of Black Cardiologists, and the National Black Nurses Association. RP Fulwood, R (reprint author), NHLBI,PUBL HLTH PROGRAM DEV,OFF PREVENT EDUC & CONTROL,31 CTR DR MSC 2480,BLDG 31,ROOM 4A05,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD AUG PY 1997 VL 8 IS 3 BP 247 EP 249 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XM898 UT WOS:A1997XM89800001 PM 9253216 ER PT J AU Ruffin, J AF Ruffin, J TI Forging alliances to meet future research and training needs SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article; Proceedings Paper CT Conference on Issues of the Heart: Prevention, Management and Control of Cardiovascular Risk Factors in African Americans CY OCT 04-05, 1996 CL MEHARRY MED COLL, NASHVILLE, TN SP Natl Heart Lung & Blood Inst HO MEHARRY MED COLL DE biomedical research; training; National Institutes of Health; Office of Research on Minority Health AB There are countless challenges in meeting the future needs of the biomedical research community. In an era of flattened research budgets, the overarching concern has become how more can be done with less. One approach, still novel for the biomedical research community but proven successful for the commercial sector, is the establishment of strategic alliances. Among federal entities, the National Institutes of Health (NIH) and the Office Of Research on Minority Health (ORMH) have as their goal the improvement of the health of the nation's minorities through support for alliances between academic research institutions. These partnerships serve to maximize an institution's opportunity for success, especially with regard to research and training. There are many different opportunities for institutions to establish partnerships, especially among minority institutions, and between minority and majority institutions. Features of successful alliances are described, working partnership models identified, and other opportunities explored. RP Ruffin, J (reprint author), NIH,OFF RES MINOR HLTH,SHANNON BLDG,ROOM 260,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD AUG PY 1997 VL 8 IS 3 BP 311 EP 316 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XM898 UT WOS:A1997XM89800011 PM 9253223 ER PT J AU Ruffin, J AF Ruffin, J TI Discussion SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Editorial Material RP Ruffin, J (reprint author), NIH,OFF RES MINOR HLTH,SHANNON BLDG,ROOM 260,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD AUG PY 1997 VL 8 IS 3 BP 316 EP 317 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA XM898 UT WOS:A1997XM89800012 ER PT J AU Read, EJ Kunitake, ST Carter, CS Chau, Q Yu, MY Klein, HG AF Read, EJ Kunitake, ST Carter, CS Chau, Q Yu, MY Klein, HG TI Enumeration of CD34+ hematopoietic progenitor cells in peripheral blood and leukapheresis products by microvolume fluorimetry: A comparison with flow cytometry SO JOURNAL OF HEMATOTHERAPY LA English DT Article AB There is increasing interest in both standardization and simplification of methods for enumeration of CD34+ hematopoietic progenitor cells (HPC) to facilitate cellular therapies and to improve interinstitutional comparison of clinical and laboratory results. We evaluated a novel method for CD34+ cell enumeration based on microvolume fluorimetry (MVF) compared with our laboratory's routine flow cytometric method on samples of peripheral blood and leukapheresis products. The MVF method is semiautomated and uses a 633-nm light from a helium-neon laser to scan fluorochrome-labeled cells held in stasis in a capillary of known volume. The performance of the MVF assay for enumeration of CD34+ cells was found to be comparable to our routine flow cytometric assay in linearity and accuracy in the range of 5-1500 cells per microliter. Precision of MVF for replicate assays on the same instrument was demonstrated by coefficient of variation (CV) values of 8.4% at a CD34+ cell concentration of 284/mu l for a sample volume of 0.8 mu l, and 15.7% at 12/mu l for a sample volume of 3.2 mu l. Precision among three different instruments was demonstrated, using sample volumes of 1.6 mu l, by CV values of 44% at 6 cells/mu l and 4.6% at 733 cells/mu l. In a field sample evaluation, precision of the entire assay system for paired measurements on 0.8-mu l sample volumes was demonstrated by CV values of 50%, 31%, and 15% for peripheral blood samples with concentrations of 0-10, 10-20, and 20-100 CD34+ cells/mu l, respectively, and 6.3%, 8.1% and 6.5% for leukapheresis samples with concentrations of 0-100, 100-1000, and 1000-2500 CD34+ cells/mu l, respectively. The MVF assay was easy to perform, required minimal technical training time, and had a turnaround time of 40 min, of which less than 10 min was actual technical time. These observations suggest that the MVF method for CD34+ cell enumeration may prove useful to clinical laboratories providing support for HPC collection, processing, and transplantation services that require relatively simple, rapid assays for product quality control or to guide real-time clinical decisions. C1 BIOMETR IMAGING INC,MT VIEW,CA 94043. RP Read, EJ (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,CELL PROC SECT,BLDG 10,ROOM 1C711,BETHESDA,MD 20892, USA. NR 16 TC 21 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1061-6128 J9 J HEMATOTHER JI J. Hematother. PD AUG PY 1997 VL 6 IS 4 BP 291 EP 301 DI 10.1089/scd.1.1997.6.291 PG 11 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA XW313 UT WOS:A1997XW31300004 PM 9377067 ER PT J AU Malide, D Dwyer, NK BlanchetteMackie, EJ Cushman, SW AF Malide, D Dwyer, NK BlanchetteMackie, EJ Cushman, SW TI Immunocytochemical evidence that GLUT4 resides in a specialized translocation post-endosomal VAMP2-positive compartment in rat adipose cells in the absence of insulin SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE GLUT4; adipose cells; insulin; immunofluorescence ID GLUCOSE-TRANSPORTER GLUT4; SYNAPTIC VESICLE PROTEINS; TRANS-GOLGI NETWORK; FACTOR-II RECEPTORS; ISOLATED FAT-CELLS; PLASMA-MEMBRANE; 3T3-L1 ADIPOCYTES; STIMULATED TRANSLOCATION; SUBCELLULAR TRAFFICKING; TRANSFERRIN RECEPTORS AB Insulin stimulates glucose transport in rat adipose cells through the translocation of GLUT4 from a poorly defined intracellular compartment to the cell surface. We employed confocal microscopy to determine the in situ localization of GLUT4 relative to vesicle, Golgi, and endosomal proteins in these physiological insulin target cells. Three-dimensional analyses of GLUT4 immunostaining in basal cells revealed an intracellular punctate, patchy distribution both in the perinuclear region and scattered throughout the cytoplasm. VAMP2 closely associates with GLUT4 in many punctate vesicle-like structures. A small fraction of GLUT4 overlaps with TGN38-mannosidase II, gamma-adaptin, and mannose-6-phosphate receptors in the perinuclear region, presumably corresponding to late endosome and trans-Golgi network structures. GLUT4 does not co-localize with transferrin receptors, clathrin, and lgp-120. After insulin treatment, GLUT4 partially redistributes to the cell surface and decreases in the perinuclear area. However, GLUT4 remains co-localized with TGN38-mannosidase II and gamma-adaptin. Therefore, the basal compartment from which GLUT4 is translocated in response to insulin comprises specialized post-endosomal VAMP2-positive vesicles, distinct from the constitutively recycling endosomes. These results are consistent with a kinetic model in which GLUT4 is sequestered through two or more intracellular pools in series. C1 NIDDK,LIPID CELL BIOL SECT,LAB CELL BIOCHEM & BIOL,NIH,BETHESDA,MD 20892. RP Malide, D (reprint author), NIDDK,DB,EDMNS,NIH,BLDG 10,RM 5N102,10 CTR DR,MSC 1420,BETHESDA,MD 20892, USA. NR 70 TC 76 Z9 77 U1 0 U2 2 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD AUG PY 1997 VL 45 IS 8 BP 1083 EP 1096 PG 14 WC Cell Biology SC Cell Biology GA XT102 UT WOS:A1997XT10200006 PM 9267469 ER PT J AU Zagorski, J Wahl, SM AF Zagorski, J Wahl, SM TI Inhibition of acute peritoneal inflammation in rats by a cytokine-induced neutrophil chemoattractant receptor antagonist SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; HIGH-LEVEL EXPRESSION; CHEMOTACTIC FACTOR; PULMONARY INFLAMMATION; CELL-LINE; IDENTIFICATION; BINDING; CHEMOKINES; DESIGN; CINC AB Cytokine-induced neutrophil chemoattractant (CINC), a member of the IL-8 superfamily of chemokines, is one rat homologue of the three human GRO proteins, Neutralizing Abs against CINC have been shown previously to be efficacious in several models of inflammation, indicating that CINC is an important proinflammatory mediator in vivo. By introducing the N-terminal mutation Delta 1-5,ELR>AAR into CINC, we have developed a rat alpha-chemokine receptor antagonist (ra) analogous to a previously described mutant of human IL-8, Bacterially expressed CINCra had no chemotactic activity itself, but completely blocked the activity of physiologic concentrations of CINC when used as an antagonist in vitro. Inhibition by CINCra was specific, since it had approximately 10-fold less antagonist activity on the related, but distinct rat alpha-chemokine macrophage-inflammatory protein 2. When coinjected with zymosan into the peritoneal cavities of Lewis rats, 100 mu g of CINCra inhibited neutrophil influx by similar to 40%, which was comparable with inhibition caused by polyclonal anti-CINC Abs. RP Zagorski, J (reprint author), NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BLDG 30,ROOM 327,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 24 Z9 24 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 AUG 1 PY 1997 VL 159 IS 3 BP 1059 EP 1062 PG 4 WC Immunology SC Immunology GA XL789 UT WOS:A1997XL78900002 PM 9233596 ER PT J AU Eischen, CM Williams, BL Zhang, WG Samelson, LE Lynch, DH Abraham, RT Leibson, PJ AF Eischen, CM Williams, BL Zhang, WG Samelson, LE Lynch, DH Abraham, RT Leibson, PJ TI ZAP-70 tyrosine kinase is required for the up-regulation of Fas ligand in activation-induced T cell apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TANDEM SH2 DOMAINS; ANTIGEN RECEPTOR; ZETA-CHAIN; LYMPHOPROLIFERATIVE SYNDROME; DEATH; MICE; MUTATIONS; SUICIDE; GENE; PHOSPHORYLATION AB Activation-induced cell death (AICD) is initiated by the TCR-dependent up-regulation of Pas ligand (Fast) mRNA., The subsequently generated soluble or cell-associated Fast gene products bind Pas, leading to apoptosis of the T cells, Although TCR stimulation is essential to initiate AICD, little is known about which TCR-initiated second messengers are required for Fast expression, We provide evidence in this work that T cells lacking the tyrosine kinase ZAP-70 are unable to up-regulate Fast and undergo AICD, Transfection of wild-type ZAP-70 into the ZAP-70-deficient T cells restores their sensitivity to TCR-induced apoptosis, whereas transfection of catalytically inactive ZAP-70 does not, These results provide clear evidence that ZAP-70 tyrosine kinase is essential in up-regulating Fast for TCR-induced apoptosis. C1 MAYO CLIN & MAYO FDN,DEPT IMMUNOL,ROCHESTER,MN 55905. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. IMMUNEX RES & DEV CORP,DEPT IMMUNOL,SEATTLE,WA 98101. FU NIGMS NIH HHS [GM47286] NR 45 TC 48 Z9 48 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 AUG 1 PY 1997 VL 159 IS 3 BP 1135 EP 1139 PG 5 WC Immunology SC Immunology GA XL789 UT WOS:A1997XL78900012 PM 9233606 ER PT J AU SloanLancaster, J Steinberg, TH Allen, PM AF SloanLancaster, J Steinberg, TH Allen, PM TI Selective loss of the calcium ion signaling pathway in T cells maturing toward a T helper 2 phenotype SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-PRESENTING CELL; ALTERED PEPTIDE LIGANDS; INDUCER LYMPHOCYTES-T; TH2 CLONES; CYTOKINE PRODUCTION; CYTOPLASMIC DOMAIN; NEGATIVE SELECTION; RECEPTOR LIGAND; ACTIVATION; COMPLEX AB In the CD4(+) T cell lineage, two well-defined differentiated populations are the Th1 and Th2 cells, which stern from a common naive T helper precursor (Thp). In this study, we begin to dissect the signaling pathways selectively used by Th1 or Th2 cells as they mature from a common naive precursor in vitro. We show that the maturing Th1 cells mount a vigorous and specific Ca2+ transient upon contact with immunogenic ligand, which is enhanced over that of the naive progenitor cells, As the cells differentiate toward a Th2 phenotype, they quickly lose the ability to engage this pathway, indicating a developmental segregation of intracellular signaling utilization, Moreover, altered peptide ligand stimulation of the Th1 line stimulates a similar Ca2+ transient as native ligand stimulation of the naive precursors, consistent with a quantitative difference in intracellular signaling by these two peptides, These data provide a direct and sequential assessment of a signaling pathway utilization in peripheral T cells as they differentiate to their final functional states. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,CTR IMMUNOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. FU NIAID NIH HHS [AI24157] NR 54 TC 68 Z9 70 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 AUG 1 PY 1997 VL 159 IS 3 BP 1160 EP 1168 PG 9 WC Immunology SC Immunology GA XL789 UT WOS:A1997XL78900015 PM 9233609 ER PT J AU Riva, A Wilson, GL Kehrl, JH AF Riva, A Wilson, GL Kehrl, JH TI In vivo footprinting and mutational analysis of the proximal CD19 promoter reveal important roles for an SP1/Egr-1 binding site and a novel site termed the PyG box SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR BSAP; B-LYMPHOCYTE DEVELOPMENT; CELL DIFFERENTIATION; GENE-EXPRESSION; SP1; ACTIVATION; ANTIGEN; MICE; INITIATION; REGULATOR AB CD19 expression begins at the pro-B cell stage of B cell development. As such it serves as a good prototype for B cell-specific genes whose expression begins shortly after lineage commitment, To understand the molecular mechanisms controlling CD19 gene expression, we isolated and functionally characterized the CD19 promoter using in vivo footprinting, gel shift assays, and transfection studies, Reporter constructs spanning portions of the promoter identified a region between -85 and -200 that produced high levels of reporter gene activity in lymphoid cells, in vivo footprinting identified protected regions over the known high affinity B cell lineage-specific activator protein (BSAP) site, the law affinity ESAP site, a SP1/Egr-1 site termed the CD19 CC box, and two novel sites named the AT box and PyG box, Phorbol ester treatment of a pre-B cell line up-regulated CD19 expression, induced Egr-1, and enhanced the footprint over the GC box, Gel shift assays demonstrated SP1 and Egr-1 binding to the CD19 GC box, while unknown nuclear proteins bound the PyG and BT boxes, Mutations in the AT box or in the BSAP sites did not affect CD19 reporter construct activity, while a mutation of the GC box reduced it modestly, and a PyG box mutation reduced it dramatically, BSAP failed to trans-activate CD19 promoter constructs in B cells or non-B cells, suggesting that cis elements such as the PyG and GC boxes are also necessary For high level CD19 promoter expression. C1 NIAID,B CELL MOL IMMUNOL SECT,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 41 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 AUG 1 PY 1997 VL 159 IS 3 BP 1284 EP 1292 PG 9 WC Immunology SC Immunology GA XL789 UT WOS:A1997XL78900030 PM 9233624 ER PT J AU Campbell, EM Proudfoot, AEI Yoshimura, T Allet, B Wells, TNC White, AM Westwick, J Watson, ML AF Campbell, EM Proudfoot, AEI Yoshimura, T Allet, B Wells, TNC White, AM Westwick, J Watson, ML TI Recombinant guinea pig and human RANTES activate macrophages but not eosinophils in the guinea pig SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CYTOKINE RANTES; EXPRESSION; CLONING; GENERATION; MIGRATION; RECEPTORS; 1-ALPHA; MOUSE; GENE AB To characterize the biologic activities of potential mediators of allergic inflammation, we have cloned, expressed, and purified guinea pig RANTES (gpRANTES). cDNA for gpRANTES was cloned from Con A-stimulated guinea pig spleen cells, A high level of gpRANTES expression in Escherichia coli was achieved by mutation of a human RANTES (hRANTES) expression construct to obtain a 68-amino acid protein identical with the predicted guinea pig amino acid sequence, assuming an equivalent amino terminus as the human protein, Purified gpRANTES was an effective stimulus of human eosinophils as assessed by increases in intracellular free calcium in fura-2-loaded cells and chemotactic responses in vitro. gpRANTES exhibits similar potency and efficacy to hRANTES, In marked contrast, neither gpRANTES nor hRANTES was able to activate guinea pig peritoneal eosinophils in these assays, even in the presence of IL-5. However, gpRANTES was found to be a potent stimulator of guinea pig peritoneal macrophages. Following tracheal instillation of gpRANTES, a dose-dependent increase In macrophages, but not eosinophils, was observed in gpBAL. Macrophage accumulation was detectable by 6 h and sustained for at least 48 h, These results indicate that RANTES in the guinea pig may have a different cellular selectivity than that described in the human, which may be important in the use of animal models in the analysis of allergic disorders. These selectivities do not appear to be accounted for by differences in guinea pig and human RANTES sequences. C1 UNIV BATH, SCH PHARM & PHARMACOL, DEPT PHARMACOL, BATH BA2 7AY, AVON, ENGLAND. GLAXO WELLCOME RES & DEV LTD, GENEVA BIOMED RES INST, GENEVA, SWITZERLAND. NCI, FREDERICK CANC RES & DEV CTR, IMMUNOBIOL LAB, IMMUNOPATHOL SECT, FREDERICK, MD 21702 USA. FU Wellcome Trust NR 34 TC 27 Z9 27 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1997 VL 159 IS 3 BP 1482 EP 1489 PG 8 WC Immunology SC Immunology GA XL789 UT WOS:A1997XL78900053 PM 9233647 ER PT J AU Ekholm, D Hemmer, B Gao, G Vergelli, M Martin, R Manganiello, V AF Ekholm, D Hemmer, B Gao, G Vergelli, M Martin, R Manganiello, V TI Differential expression of cyclic nucleotide phosphodiesterase 3 and 4 activities in human T cell clones specific for myelin basic protein SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; AUTOIMMUNE ENCEPHALOMYELITIS; CAMP-PHOSPHODIESTERASE; LYMPHOKINE PRODUCTION; SELECTIVE INHIBITORS; MOLECULAR-CLONING; HUMAN-LYMPHOCYTES; ELEVATING AGENTS; GENE-EXPRESSION; HUMAN CD4+ AB Little is known concerning the relative distribution and function of the different cyclic nucleotide phosphodiesterases (PDEs) in lymphocytes. Recent reports, however, have indicated that specific PDE4 inhibitors were effective in treatment of experimental allergic encephalomyelitis, an animal model of multiple sclerosis. The therapeutic effect of PDE4 inhibitors is thought to be related to inhibition of autoreactive CD4(+) T cells specific for myelin basic protein (MBP) or other myelin proteins. Human autoreactive CD4(+) T lymphocyte clones (TCC), specific for the immunodominant MEP epitope (amino acids 83-99), contain PDE3 and PDE4, two PDEs that exhibit a high affinity for cAMP, Amplification of TCC mRNA by reverse transcription-PCR indicated that TCC PDE3 mRNA was of the PDE3B, not PDE3A, subtype. Different TCC contained different proportions of PDES and PDE4, and their activities increased during Ag (MBP) stimulation. Specific PDE3 (cilostamide) and PDE4 (rolipram) inhibitors suppressed [H-3]thymidine incorporation in TCC, Since it is believed that many autoimmune diseases are at least partially mediated by autoreactive CD4(+) T cells, these observations may have important implications not only for the treatment of multiple sclerosis but also for other autoimmune diseases. C1 NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. LUND UNIV,SECT MOL SIGNALING,DEPT CELL & MOL BIOL,LUND,SWEDEN. UNIV TUBINGEN,DEPT NEUROL,D-7400 TUBINGEN,GERMANY. NR 64 TC 44 Z9 46 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 AUG 1 PY 1997 VL 159 IS 3 BP 1520 EP 1529 PG 10 WC Immunology SC Immunology GA XL789 UT WOS:A1997XL78900057 PM 9233651 ER PT J AU Shibata, R Maldarelli, F Siemon, C Matano, T Parta, M Miller, G Fredrickson, T Martin, MA AF Shibata, R Maldarelli, F Siemon, C Matano, T Parta, M Miller, G Fredrickson, T Martin, MA TI Infection and pathogenicity of chimeric simian-human immunodeficiency viruses in macaques: Determinants of high virus loads and CD4 cell killing SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th Annual Symposium on Nonhuman Primate Models for AIDS CY OCT 23-26, 1996 CL PORTLAND, OR SP US Public Hlth Serv, Natl Ctr Res Resources, Natl Inst Allergy & Infect Dis, NIH, Oregon Reg Primate Res Ctr, Chiron Biocine, Immunotech, A Coulter Co, TSI Mason Lab ID MOLECULAR CLONES; PERSISTENT INFECTION; CYNOMOLGUS MONKEYS; TYPE-1 ISOLATE; RHESUS-MONKEYS; IN-VIVO; AIDS; GENE; RETROVIRUS; DISEASE AB Chimeric simian-human immunodeficiency viruses (SHIVs) carrying envelope glycoproteins derived from a T cell-macrophage dual-tropic primary isolate (human immunodeficiency virus type 1 [HIV-1] strain DH12) were constructed, When inoculated into macaque monkeys, SHIVMD14 carrying simian immunodeficiency virus-derived nef established significantly higher virus loads than did SHIVMD1, which contains the HIV-1 nef gene, Three patterns of CD4 cell depletion were observed in infected monkeys: exponential and irreversible loss to undetectable levels within 10 weeks of infection; marked reduction during acute infection followed by partial recovery and stabilization (lasting from 10 weeks to >1 year), with a later decline to undetectable levels in some animals; and a transient loss during acute infection, The induced immunodeficiency was accompanied by CD4 cell counts of <50 cells/mu L and was associated with Pneumocystis carinii pneumonia, cytomegalovirus meningoencephalitis, lymphoid depletion, and thymic atrophy. C1 NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,NIH,BETHESDA,MD 20892. RP Shibata, R (reprint author), NIAID,MOL MICROBIOL LAB,NIH,9000 ROCKVILLE PIKE,BLDG 4,ROOM 305,BETHESDA,MD 20892, USA. NR 27 TC 142 Z9 142 U1 10 U2 21 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 AUG PY 1997 VL 176 IS 2 BP 362 EP 373 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XW859 UT WOS:A1997XW85900008 PM 9237701 ER PT J AU Martin, LN MurpheyCorb, M Mack, P Baskin, GB Pantaleo, G Vaccarezza, M Fox, CH Fauci, AS AF Martin, LN MurpheyCorb, M Mack, P Baskin, GB Pantaleo, G Vaccarezza, M Fox, CH Fauci, AS TI Cyclosporin A modulation of early virologic and immunologic events during primary simian immunodeficiency virus infection in rhesus monkeys SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th International Conference on Antiviral Research CY APR, 1995 CL SANTA FE, NM ID T-CELL ACTIVATION; CYCLOPHILIN-A; AUTOIMMUNE-DISEASE; HIV-1 INFECTION; IMMUNE-SYSTEM; LYMPHOCYTES-T; AIDS; TYPE-1; MACAQUES; RETROVIRUS AB Virologic and immunologic effects of immunomodulation during primary simian immunodeficiency virus (SIV) infection were examined in monkeys treated with cyclosporin or vehicle for 32 days beginning 5 days before SIV inoculation, Duration of antigenemia decreased in 5 of 7 treated monkeys, 2 having delayed onset and peak of antigenemia, Although proviral DNA levels in blood and lymph nodes and infected cell numbers in lymph nodes were transiently decreased, levels were similar to those in controls by day 14. The CD4:CD8 ratio and percentage of CD4(+)CD29(+) cells decreased in controls 14 days after inoculation, but this decrease was delayed in treated monkeys, Two treated monkeys demonstrated rapid disease, with progressive antigenemia preceding early deaths 90-96 days after inoculation. Nevertheless, immunomodulation influenced the kinetics of primary SIV infection in some monkeys, supporting the rationale of careful exploration of the strategy of interference with the heightened state of cellular activation together with direct antiretroviral therapy in human immunodeficiency virus infection. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. MOL HISTOL INC,GAITHERSBURG,MD. RP Martin, LN (reprint author), TULANE UNIV,TULANE REG PRIMATE RES CTR,DEPT MICROBIOL,18703 THREE RIVERS RD,COVINGTON,LA 70433, USA. OI VACCAREZZA, Mauro/0000-0003-3060-318X FU NCRR NIH HHS [RR-00164]; NIAID NIH HHS [AI-15119] NR 63 TC 34 Z9 34 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 AUG PY 1997 VL 176 IS 2 BP 374 EP 383 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XW859 UT WOS:A1997XW85900009 PM 9237702 ER PT J AU Hershow, RC Riester, KA Lew, J Quinn, TC Mofenson, LM Davenny, K Landesman, S Cotton, D Hanson, IC Hillyer, GV Tang, HB Thomas, DL AF Hershow, RC Riester, KA Lew, J Quinn, TC Mofenson, LM Davenny, K Landesman, S Cotton, D Hanson, IC Hillyer, GV Tang, HB Thomas, DL TI Increased vertical transmission of human immunodeficiency virus from hepatitis C virus-coinfected mothers SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT XIth International Conference on AIDS CY JUL 07-13, 1996 CL VANCOUVER, CANADA ID MATERNAL-INFANT TRANSMISSION; INTRAVENOUS-DRUG-USERS; NON-B-HEPATITIS; NON-A; DISEASE PROGRESSION; INFECTION; HIV; RISK; ASSOCIATION; ANTIBODIES AB To determine if hepatitis C virus (HCV) infection affects vertical transmission of human immunodeficiency virus (HIV), 487 HIV-infected pregnant women in the prospective, multicenter, Women and Infants Transmission Study had HCV antibody (anti-HCV by second-generation ELISA) and HCV RNA (by quantitative polymerase chain reaction) measured in peripartum maternal plasma; 161 (33%) were anti-HCV-positive, HIV vertical transmission occurred from 42 HCV-infected mothers (26.1%) versus 53 HCV-uninfected mothers (16.3%; odds radio [OR], 1.82; P = .01). In a logistic regression model that included maternal drug use, a potential confounder, HCV infection was marginally associated with perinatal HIV transmission (OR, 1.64; P = .05), whereas drug use was not, Women who transmitted HIV had higher levels of HCV RNA (median, 721,254 copies/mL) than those who did not (337,561 copies/mL; P = .01), Maternal HCV infection is associated with increased HIV vertical transmission. Further studies are needed to ascertain if HCV directly affects perinatal HIV transmission or is a marker for another factor, such as maternal drug use. C1 UNIV ILLINOIS,COLL MED,CHICAGO,IL 60612. NEW ENGLAND RES INST,WATERTOWN,MA. MASSACHUSETTS GEN HOSP,DEPT MED,INFECT DIS UNIT,BOSTON,MA 02114. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,NIH,ROCKVILLE,MD. NIDA,NIH,ROCKVILLE,MD. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. SUNY HLTH SCI CTR,DIV INFECT DIS,BROOKLYN,NY 11203. COLUMBIA UNIV COLL PHYS & SURG,DEPT PEDIAT,NEW YORK,NY 10032. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. UNIV PUERTO RICO,SAN JUAN,PR 00936. RP Hershow, RC (reprint author), UNIV ILLINOIS,SCH PUBL HLTH,ROOM 504,2121 W TAYLOR ST,CHICAGO,IL 60612, USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [AI-34842, AI-34840, AI-34856] NR 44 TC 60 Z9 61 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1997 VL 176 IS 2 BP 414 EP 420 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XW859 UT WOS:A1997XW85900013 PM 9237706 ER PT J AU Deeks, SG Coleman, RL White, R Pachl, C Schambelan, M Chernoff, DN Feinberg, MB AF Deeks, SG Coleman, RL White, R Pachl, C Schambelan, M Chernoff, DN Feinberg, MB TI Variance of plasma human immunodeficiency virus type 1 RNA levels measured by branched DNA within and between days SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd National Conference on Retroviruses and Opportunistic Infections CY JAN 28-FEB 02, 1996 CL WASHINGTON, DC ID HUMAN PERIPHERAL-BLOOD; LYMPHOCYTE COUNT; INFECTION; ANTIGEN; LOAD AB Previous studies have shown that CD4-positive T cells vary in a predictable manner over 24 h. This diurnal variance has significant clinical implications, Recently, viral RNA measurements have been increasingly used as a standard marker in the management of human immunodeficiency virus (HIV)-infected patients, Little detailed analysis of the variability of this marker has been conducted. To define the variance of plasma HIV-1 RNA levels within days, 11 clinically stable patients with established HIV infection and a baseline viral RNA level >40,000 copies/ml were studied, Following the patients' admission to an inpatient research unit, plasma samples were obtained frequently over 48 h and analyzed for HIV-1 RNA levels by use of a quantitative branched chain DNA assay (bDNA), No diurnal pattern was detected, In these clinically stable patients, viral RNA levels exhibited a variance of similar to 0.4 log. C1 CHIRON CORP,EMERYVILLE,CA 94608. NIH,OFF AIDS RES,BETHESDA,MD 20892. RP Deeks, SG (reprint author), UNIV CALIF SAN FRANCISCO,SAN FRANCISCO GEN HOSP,AIDS PROGRAM,995 POTRERO AVE,SAN FRANCISCO,CA 94110, USA. FU NCRR NIH HHS [RR-00083]; NIAID NIH HHS [AI-27763]; NIDDK NIH HHS [DK-45833] NR 14 TC 25 Z9 25 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1997 VL 176 IS 2 BP 514 EP 517 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA XW859 UT WOS:A1997XW85900028 PM 9237721 ER PT J AU Blauvelt, A Zaitseva, M Zoeteweij, JP Lee, S Lapham, CK Manischewitz, J KlausKovtun, V AF Blauvelt, A Zaitseva, M Zoeteweij, JP Lee, S Lapham, CK Manischewitz, J KlausKovtun, V TI Surface expression of CCR-5, but not CXCR-4, on freshly isolated Langerhans cells (LC) correlates with restricted transmission of macrophage (M)-tropic HIV. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. US FDA,DIV VIRAL PROD,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 109 IS 2 BP 5 EP 5 PG 1 WC Dermatology SC Dermatology GA XM195 UT WOS:A1997XM19500026 ER PT J AU Jakob, T Udey, MC AF Jakob, T Udey, MC TI E-cadherin-mediated adhesion in Langerhans cell-like dendritic cells is regulated by cytokines that mobilize Langerhans cells in vivo. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 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 AUG PY 1997 VL 109 IS 2 BP 24 EP 24 PG 1 WC Dermatology SC Dermatology GA XM195 UT WOS:A1997XM19500047 ER PT J AU Masunaga, T Shimizu, H Yee, C Borradori, L Lazarova, Z Nishikawa, T Yancey, KB AF Masunaga, T Shimizu, H Yee, C Borradori, L Lazarova, Z Nishikawa, T Yancey, KB TI The extracellular domain of BPAG2 localizes to anchoring filaments and its carboxyl terminus extends to the lamina densa of normal human epidermal basement membrane SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE hemidesmosomes; collagen; laminin ID BULLOUS PEMPHIGOID ANTIGEN; IMMUNOELECTRON MICROSCOPY; EPIDERMOLYSIS-BULLOSA; ADHESION; INTEGRIN; AUTOANTIBODIES; RECEPTOR; COLLAGEN; PROTEIN; KALININ AB Bullous pemphigoid antigen 2 (BPAG2) is a 180 kDa type II transmembrane protein associated with hemidesmosomes (HDs) in basal keratinocytes, To better understand how BPAG2 promotes keratinocyte adhesion to epidermal basement membrane (BM), purified IgG against a baculovirus-encoded recombinant was used to localize its carboxyl terminus in human skin by immunogold electron microscopy (DEM). A 2.1-kb BPAG2 cDNA encoding the distal extracellular domain and carboxyl terminus of BPAG2 was used in a baculovirus expression system to create virus that produced a 70-kDa recombinant form of BPAG2 (BV4). BV4 was purified, characterized, and used to raise high-titer specific rabbit IgG, Purified anti-BV4 IgG bound the epidermal side of 1 M NaCl split skin and bound only BPAG2 on immunoblots containing extracts of human keratinocytes, In IEM studies of pre- and post-embedded skin, the distal ectodomain of BPAG2 localized beneath HDs in basal keratinocytes; there was no evidence of BPAG2 beneath melanocytes. Anti-BV4 IgG extensively bound anchoring filaments on the epidermal side of 1 M NaCl split skin; this staining extended along anchoring filaments to their ends, In post-embedded skin, the carboxyl terminus of BPAG2 was localized within the lamina densa, 41 nm (mean of 400 determinations) beneath plasma membranes of basal keratinocytes. BPAG2 thus extends from the intracellular PID plaque of basal keratinocytes to the lamina densa of human epidermal BM. C1 NCI,DERMATOL BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. KEIO UNIV,SCH MED,DEPT DERMATOL,TOKYO,JAPAN. KOSE CORP,BASIC RES LAB,TOKYO,JAPAN. RI Shimizu, Hiroshi/A-5193-2012 NR 43 TC 85 Z9 85 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 1997 VL 109 IS 2 BP 200 EP 206 DI 10.1111/1523-1747.ep12319337 PG 7 WC Dermatology SC Dermatology GA XM195 UT WOS:A1997XM19500013 PM 9242508 ER PT J AU Spritz, RA Ho, LL Furumura, M Hearing, VJ AF Spritz, RA Ho, LL Furumura, M Hearing, VJ TI Mutational analysis of copper binding by human tyrosinase SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE albinism; hemocyanin; melanogenesis ID AMINO-ACID-SEQUENCE; OCULOCUTANEOUS ALBINISM; NUCLEOTIDE-SEQUENCE; POLYPHENOL OXIDASE; MAMMALIAN TYROSINASE; NEUROSPORA TYROSINASE; MOLECULAR-CLONING; MOUSE TYROSINASE; ACTIVE-SITES; GENE AB Tyrosinase (EC 1.14.18.1) is a copper-containing enzyme that catalyzes several reactions in the biosynthesis of melanin pigments and is deficient in patients with type I oculocutaneous albinism (OCA1), Tyrosinase is thought to bind two copper ions, one at each of two conserved sequence motifs, termed CuA and CuB, but to date this has been directly proved only for the Neurospora and mushroom enzyme. Here, we demonstrate that mammalian tyrosinase directly binds copper, and that the CuA and CuB sites are both required for copper binding and for catalytic activity. We show that in human tyrosinase, copper binding by the CuB site is most Likely coordinated by residues His363, His367, and His389, and that copper binding may be cooperative, with copper binding at one site facilitating copper binding by the other site. Furthermore, correct folding of the tyrosinase polypeptide appears to be necessary for copper binding, and a number of human OCA1 mutations disrupt copper binding and thus catalytic function of tyrosinase. C1 UNIV WISCONSIN,DEPT PEDIAT,GENET LAB,MADISON,WI 53706. NIH,CELL BIOL LAB,BETHESDA,MD 20892. RP Spritz, RA (reprint author), UNIV WISCONSIN,DEPT MED GENET,GENET LAB,445 HENRY MALL,MADISON,WI 53706, USA. FU NIAMS NIH HHS [AR39892] NR 57 TC 55 Z9 59 U1 2 U2 5 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 AUG PY 1997 VL 109 IS 2 BP 207 EP 212 DI 10.1111/1523-1747.ep12319351 PG 6 WC Dermatology SC Dermatology GA XM195 UT WOS:A1997XM19500014 PM 9242509 ER PT J AU Bryant, SD Guerrini, R Salvadori, S Bianchi, C Tomatis, R Attila, M Lazarus, LH AF Bryant, SD Guerrini, R Salvadori, S Bianchi, C Tomatis, R Attila, M Lazarus, LH TI Helix-inducing alpha-aminoisobutyric acid in opioid mimetic deltorphin C analogues SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID AMINO-ACIDS; RECEPTOR SELECTIVITY; AMPHIBIAN SKIN; HIGH-AFFINITY; CONFORMATIONAL PREFERENCES; OLIGOPEPTIDES RICH; DELTA-SELECTIVITY; LIGAND-BINDING; PEPTIDES; MU AB The achiral symmetric alpha-aminoisobutyric acid (Aib) replaced the critical N-terminal residues of the amphibian skin opioid deltorphin C (H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) without detriment to the physicochemical requirements for delta opioid receptor recognition. Substitutions by the alpha,alpha-dialkyl amino acid in place of D-Ala(2) or Phe(3), or both, exhibited high delta receptor affinity (K-i delta = 0.12-3.6 nM) and 5-9-fold greater selectivity (K-i mu/K-i delta = 5000-8500) than the parent compound. This is the first definitive demonstration that the D-chirality of alanine and the aromaticity of phenylalanine are replaceable by an achiral alpha,alpha-dialkylated residue without detrimental effects on ligand binding. Incorporation of the mono-alpha-alkyl amino acid L- or D-Ala at the third position also produced highly selective delta ligands (K-i mu/K-i delta = 2000-3500), albeit with reduced delta affinities (K-i delta = 6-15 nM). Replacement of the anionic residue Asp(4) by Aib yielded an opioid peptide that fit two-site binding models for the delta receptor (eta = 0.763; P < 0.0001) and displayed dual high affinity for both delta and mu receptors, emphasizing the repulsive effect by a negative charge at mu receptor sites and the insignificance of Asp for delta affinity. Molecular dynamics conformational analyses suggested that Aib residues caused distinct changes in deltorphin C secondary structure when substituted for D-Ala(2), Asp(4) and simultaneously D-Ala(2) and Phe(3) but not when substituted for Phe(3). These conformational changes might be critical factors for the proper orientation of reactive constituents of residues in the N-terminal region of deltorphin C. Disparities between binding data and functional bioassays of [Aib(3)] indicated that Phe(3) was required for bioactivity in mouse vas deferens but not for interaction with delta opioid receptors in rat brain membranes. C1 UNIV FERRARA, INST PHARMACOL, I-44100 FERRARA, ITALY. UNIV FERRARA, DEPT PHARMACEUT SCI, I-44100 FERRARA, ITALY. UNIV FERRARA, CTR BIOTECHNOL, I-44100 FERRARA, ITALY. UNIV HELSINKI, FAC VET MED, DEPT CLIN SCI PHARMACOL & TOXICOL, FIN-00014 HELSINKI, FINLAND. RP Bryant, SD (reprint author), NIEHS, PEPTIDE NEUROCHEM GRP, POB 12233, MD C3-04, RES TRIANGLE PK, NC 27709 USA. OI Guerrini, Remo/0000-0002-7619-0918 NR 92 TC 22 Z9 22 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 1 PY 1997 VL 40 IS 16 BP 2579 EP 2587 DI 10.1021/jm9700530 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XP087 UT WOS:A1997XP08700018 PM 9258365 ER PT J AU Jiang, QL Lee, BX Glashofer, M vanRhee, AM Jacobson, KA AF Jiang, QL Lee, BX Glashofer, M vanRhee, AM Jacobson, KA TI Mutagenesis reveals structure-activity parallels between human A(2A) adenosine receptors and biogenic amine G protein-coupled receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; LIGAND-BINDING-SITE; BETA-ADRENERGIC-RECEPTOR; TRANSMEMBRANE DOMAIN; 3-DIMENSIONAL MODELS; ANTAGONIST BINDING; IDENTIFICATION; RESIDUES; AGONIST; ACTIVATION AB Structure-affinity relationships for ligand binding at the human A(2A) adenosine receptor have been probed using site-directed mutagenesis in the transmembrane helical domains (TMs). The mutant receptors were expressed in COS-7 cells and characterized by binding of the radioligands [H-3]CGS21680; [H-3]NECA, and [H-3]XAC. Three residues, at positions essential for ligand binding in other G protein-coupled receptors, were individually mutated. The residue V(3.32) in the A(2A) receptor that is homologous to the essential aspartate residue of TM3 in the biogenic amine receptors, i.e., V84(3.32), may be substituted with L (present in the A(3) receptor) but not with D (in biogenic amine receptors) or A. H250(6.52), homologous to the critical N507 of rat m3 muscarinic acetylcholine receptors, may be substituted with other aromatic residues or with N but not with A (Kim et al. J. Biol. Chem. 1995, 270, 13987-13997). H278(7.43) homologous to the covalent ligand anchor site in rhodopsin, may not be substituted with either A, K, or N. Both V84L(3.32) and H250N(6.52) mutant receptors were highly variable in their effect on ligand competition depending on the structural class of the ligand. Adenosine-5'-uronamide derivatives were more potent at the H250N(6.52) mutant receptor than at wild type receptors. Xanthines tended to be close in potency (H250N(6.52)) or less potent (V84L(3.32)) than at wild type receptors. The affinity of CGS21680 increased as the pH was lowered to 5.5 in both the wild type and H250N(6.52) mutant receptors. Thus, protonation of H250(6.52) is not involved in this pH dependence. These data are consistent with a molecular model predicting the proximity of bound agonist ligands to TM3, TM5, TM6, and TM7. C1 NIDDK,MOL RECOGNIT SECT,LBC,NIH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 50 TC 55 Z9 55 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 1 PY 1997 VL 40 IS 16 BP 2588 EP 2595 DI 10.1021/jm970084v PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XP087 UT WOS:A1997XP08700019 PM 9258366 ER PT J AU Jiang, JL vanRhee, AM Chang, L Patchornik, A Ji, XD Evans, P Melman, N Jacobson, KA AF Jiang, JL vanRhee, AM Chang, L Patchornik, A Ji, XD Evans, P Melman, N Jacobson, KA TI Structure-activity relationships of 4-(phenylethynyl)-6-phenyl-1,4-dihydropyridines as highly selective A(3) adenosine receptor antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; MAST-CELLS; RAT-BRAIN; AFFINITY AB 4-(Phenylethynyl)-6-phenyl-1,4-dihydropyridine derivatives are selective antagonists at human A(3) adenosine receptors, with K-i values in a radioligand binding assay vs [I-125]AB-MECA (N-6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine) in the submicromolar range. In this study, structure-activity relationships at various positions of the dihydropyridine ring (the 3- and 5-acyl substituents, the 4-aryl substituent, and 1-methyl group) were probed synthetically. Using the combined protection of the l-ethoxymethyl and the 5-[2-(trimethylsilyl)ethyl] ester groups, a free carboxylic acid was formed at the 5-position allowing various substitutions. Selectivity of the new analogues for cloned human A(3) adenosine receptors was determined vs radioligand binding at rat brain A(1) and A(2A) receptors. Structure-activity analysis at adenosine receptors indicated that pyridyl, furyl, benzofuryl, and thienyl groups at the 4-position resulted in, at most, only moderate selectivity for A(3) adenosine receptors. Ring substitution (e.g., 4-nitro) of the 4-phenylethynyl group did not provide enhanced selectivity, as it did for the 4-styryl-substituted dihydropyridines. At the 3-position of the dihydropyridine ring, esters were much more selective for A(3) receptors than closely related thioester, amide, and ketone derivatives. A cyclic 3-keto derivative was 5-fold more potent at A(3) receptors than a related open-ring analogue. At the 5-position, a homologous series of phenylalkyl esters and a series of substituted benzyl esters were prepared and tested. (Trifluoromethyl)-, nitro-, and other benzyl eaters substituted with electron-withdrawing groups were specific for A(3) receptors with nanomolar K-i values and selectivity as high as 37000-fold. A functionalized congener bearing an [(aminoethyl)amino]carbonyl group was also prepared as an intermediate in the synthesis of biologically active conjugates. C1 NIDDK, MOL RECOGNIT SECT, LBC, NIH, BETHESDA, MD 20892 USA. POLY CHEM PCJ, NESS ZIONA, ISRAEL. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 35 TC 80 Z9 80 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 1 PY 1997 VL 40 IS 16 BP 2596 EP 2608 DI 10.1021/jm970091j PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XP087 UT WOS:A1997XP08700020 PM 9258367 ER PT J AU Mushegian, AR Koonin, EV AF Mushegian, AR Koonin, EV TI Polyphyletic gene losses can bias backtrack characterizations of the cenancestor - Response SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Editorial Material C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. NR 6 TC 1 Z9 1 U1 1 U2 1 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 AUG PY 1997 VL 45 IS 2 BP 117 EP 118 DI 10.1007/PL00006201 PG 2 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA XN368 UT WOS:A1997XN36800002 ER PT J AU Bienfait, B Gasteiger, J AF Bienfait, B Gasteiger, J TI Checking the projection display of multivariate data with colored graphs SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article DE principal component analysis; PCA; nonlinear mapping; NLM; self-organizing map; SOM; Kohonen's network; minimal spanning tree; MST; k-largest distortions graph; k-LDG; interatomic distances; histogram; frequency distribution; autocorrelation; QSAR AB Projection methods such as principal component analysis (PCA), nonlinear mapping (NLM), and the self-organizing map (SOM) are valuable algorithms for visualizing multi dimensional data in a two-dimensional plane. Unfortunately, the reduction of the dimensionality involves distortions. In all attempt to graphically localize the distortions of the projected data, we suggest superposing colored graphs onto the 2D plots. The color of the edges of these graphs encodes the original high-dimensional distances between the connected points. The method is applied to a cluster analysis of 37 biologically active compounds and 471 molecules represented by a structural 3D descriptor. (C) 1998 by Elsevier Science Inc. C1 Univ Erlangen Nurnberg, Inst Organ Chem, Comp Chem Ctr, D-91052 Erlangen, Germany. RP NCI, Med Chem Lab, NIH, Bldg 37,Room 5B20, Bethesda, MD 20892 USA. NR 25 TC 20 Z9 20 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1093-3263 EI 1873-4243 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD AUG PY 1997 VL 15 IS 4 BP 203 EP + DI 10.1016/S0263-7855(97)00078-7 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA ZB928 UT WOS:000072522400001 PM 9524929 ER PT J AU Pettit, GR Xu, JP Hogan, F Williams, MD Doubek, DL Schmidt, JM Cerny, RL Boyd, MR AF Pettit, GR Xu, JP Hogan, F Williams, MD Doubek, DL Schmidt, JM Cerny, RL Boyd, MR TI Isolation and structure of the human cancer cell growth inhibitory cyclodepsipeptide dolastatin 16 SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID HARE DOLABELLA-AURICULARIA; ANTINEOPLASTIC AGENTS; SOLUTION-STATE; SEPARATION; PEPTIDES; SCREEN AB An investigation of the sea hare Dolabella auricularia from Papua New Guinea has led to discovery of the new cyclodepsipeptide dolastatin 16 (3) containing two new amino acid units designated dolamethylleuine (Dml) and dolaphenvaline (Dpv). The structural elucidation was achieved by means of high-field (500 MHz) NMR and tandem MS/MS mass spectral interpretations and allowed the assignment cyclo-(Pro-Dpv-Pro-Dml-O-Lac-Pro-O-Hiv-MeVal). The new depsipetide exhibited strong inhibition of growth against a variety of human cancer cell lines. C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. UNIV NEBRASKA,NEBRASKA CTR MASS SPECTROMETRY,LINCOLN,NE 68588. NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DTP,DCTDC,FREDERICK,MD 21701. RP Pettit, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA. FU NCI NIH HHS [CA44344-01-09] NR 18 TC 40 Z9 45 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD AUG PY 1997 VL 60 IS 8 BP 752 EP 754 DI 10.1021/np9700230 PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA XT789 UT WOS:A1997XT78900002 PM 9287413 ER PT J AU Armstrong, JG Putnam, FW Carlson, EB Libero, DZ Smith, SR AF Armstrong, JG Putnam, FW Carlson, EB Libero, DZ Smith, SR TI Development and validation of a measure of adolescent dissociation: The adolescent dissociative experiences scale SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID CHILD AB This study describes the initial reliability and validity data on the Adolescent Dissociative Experiences Scale (A-DES), a screening measure for pathological dissociation during adolescence. The A-DES showed good scale and subscale reliability, and, as hypothesized, increased scores were associated with reported trauma in a patient population. A-DES scores were able to distinguish dissociative disordered adolescents from a normal sample and from a patient sample with a variety of diagnoses. C1 UNIV SO CALIF,DEPT PSYCHOL,LOS ANGELES,CA 90089. NIMH,UNIT DEV TRAUMATOL,BETHESDA,MD 20892. SHEPPARD & ENOCH PRATT HLTH SYST,BALTIMORE,MD. UNIV ARKANSAS,DEPT PSYCHOL,FAYETTEVILLE,AR 72701. RI Carlson, Eve/E-3520-2010 OI Carlson, Eve/0000-0002-4431-2415 NR 12 TC 138 Z9 139 U1 0 U2 15 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD AUG PY 1997 VL 185 IS 8 BP 491 EP 497 DI 10.1097/00005053-199708000-00003 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XR353 UT WOS:A1997XR35300003 PM 9284862 ER PT J AU Chalazonitis, A Tennyson, VM Kibbey, MC Rothman, TP Gershon, MD AF Chalazonitis, A Tennyson, VM Kibbey, MC Rothman, TP Gershon, MD TI The alpha 1 subunit of laminin-1 promotes the development of neurons by interacting with LBP110 expressed by neural crest-derived cells immunoselected from the fetal mouse gut SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE enteric nervous system; neural crest; laminin; immunoselection; c-fos ID ENTERIC NERVOUS-SYSTEM; PRESUMPTIVE AGANGLIONIC BOWEL; ENDOTHELIN-B RECEPTOR; BINDING-PROTEIN; SYNTHETIC PEPTIDE; MICE LACKING; HOST EMBRYOS; MUTANT MICE; IKVAV SITE; A-CHAIN AB A plasmalemmal protein, LDP110, which hinds to the alpha 1 chain of laminin-1, is acquired by the neural crest-derived precursors of enteric neurons after they colonize the gut, We tested the hypothesis that laminin-1 interacts with LBP110 to promote enteric neuronal development, The effects of laminin-1 on neuronal development were studied in cultures of cells immunoselected from fetal mouse gut (E14-15) with antibodies to LBP110 or p7S(NTR), a marker for enteric crest-derived cells, No matter which antibody was used, the development of cells expressing neuronal markers was increased three- to fourfold by culturing the cells on a laminin-1-containing substrate, To determine whether this effect of laminin-1 is due to the selective adherence of a neurocompetent subset of precursors, immunoselected cells were permitted to preadhere to poly-D-lysine. Addition of soluble laminin-1 24 h later promoted neuronal but glial development. The laminin-1-induced increment in neuronal development was abolished both by a peptide containing the sequence a the LRP110-binding domain, IKVAV, and by antibodies to laminin alpha 1 that recognize the IKVAV domain, Neither reagent affected the total number of cells, In contrast, the response to laminin-1 was not affected by control peptides, preimmune sera, or antibodies to laminin beta 1. Laminin-1 transiently induced the expression of nuclear Fos immunoreactivity; this action mas blocked specifically by the IKVAV peptide. These data are consistent with the hypothesis that LBP110 interacts with the IKVAV domain of laminin alpha 1 to promote the differentiation of neurons from enteric crest-derived precursors. (C) 1997 John Wiley & Sons, Inc. C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT ANAT & CELL BIOL,NEW YORK,NY 10032. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. FU NICHD NIH HHS [HD 20470, HD17736]; NINDS NIH HHS [NS15547] NR 65 TC 52 Z9 58 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD AUG PY 1997 VL 33 IS 2 BP 118 EP 138 DI 10.1002/(SICI)1097-4695(199708)33:2<118::AID-NEU2>3.0.CO;2-5 PG 21 WC Neurosciences SC Neurosciences & Neurology GA XM190 UT WOS:A1997XM19000002 PM 9240369 ER PT J AU Blanc, EM Kelly, JF Mark, RJ Waeg, G Mattson, MP AF Blanc, EM Kelly, JF Mark, RJ Waeg, G Mattson, MP TI 4-hydroxynonenal, an aldehydic product of lipid peroxidation, impairs signal transduction associated with muscarinic acetylcholine and metabotropic glutamate receptors: Possible action on G alpha(q/11) SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; antioxidants; calcium homeostasis; cerebral ischemia; endoplasmic reticulum; glutathione; inositol phosphate; phospholipase C; stroke; vitamin E ID LONG-TERM POTENTIATION; AMYLOID PRECURSOR PROTEIN; POSTMORTEM HUMAN BRAIN; K-M GTPASE; ALZHEIMERS-DISEASE; HIPPOCAMPAL-NEURONS; PHOSPHOINOSITIDE HYDROLYSIS; SECRETED FORMS; FREE-RADICALS; CELL-CULTURE AB Considerable data indicate that oxidative stress and membrane lipid peroxidation contribute to neuronal degeneration in an array of age-related neurodegenerative disorders. In contrast, the impact of subtoxic levels of membrane lipid peroxidation on neuronal function is largely unknown. We now report that 4-hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, disrupts coupling of muscarinic cholinergic receptors and metabotropic glutamate receptors to phospholipase C-linked GTP-binding proteins in cultured rat cerebrocortical neurons. At subtoxic concentrations, HNE markedly inhibited GTPase activity, inositol phosphate release, and elevation of intracellular calcium levels induced by carbachol (muscarinic agonist) and (RS)-3,5-dihydroxyphenyl glycine (metabotropic glutamate receptor agonist). Maximal impairment of agonist-induced responses occurred within 30 min of exposure to HNE. Other aldehydes, including malondialdehyde, had little effect on agonist-induced responses. Antioxidants that suppress lipid peroxidation did not prevent impairment of agonist-induced responses by HNE, whereas glutathione, which is known to bind and detoxify HNE, did prevent impairment of agonist-induced responses. HNE itself did not induce oxidative stress. Immunoprecipitation-western blot analysis using an antibody to HNE-protein conjugates showed that HNE can bind to G alpha(q/11). HNE also significantly suppressed inositol phosphate release induced by aluminum fluoride. Collectively, our data suggest that HNE plays a role in altering receptor-G protein coupling in neurons under conditions of oxidative stress that may occur both normally, and before cell degeneration and death in pathological settings. C1 UNIV KENTUCKY,SANDERS BROWN CTR AGING,LEXINGTON,KY 40536. UNIV KENTUCKY,DEPT ANAT & NEUROBIOL,LEXINGTON,KY 40536. NIH,CTR GERONTOL RES,BALTIMORE,MD. GRAZ UNIV,INST BIOCHEM,A-8010 GRAZ,AUSTRIA. RI Mattson, Mark/F-6038-2012 FU NIA NIH HHS [AG14554]; NINDS NIH HHS [NS29001] NR 74 TC 113 Z9 115 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 AUG PY 1997 VL 69 IS 2 BP 570 EP 580 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XL154 UT WOS:A1997XL15400013 PM 9231714 ER PT J AU Moller, JR Durr, PG Quarles, RH Duncan, ID AF Moller, JR Durr, PG Quarles, RH Duncan, ID TI Biochemical analysis of myelin proteins in a novel neurological mutant: The Taiep rat SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE myelin; microtubule; hypomyelinating mutant; myelin-associated glycoprotein; Taiep ID NERVOUS-SYSTEM; GLYCOPROTEIN; MICE; HETEROSIS; DEFICIENT; MEMBRANES; BRAIN AB Hemispheres, spinal cords, and sciatic nerves were taken from taiep, carrier, and control rats at ages ranging from 1 day to 16 months. Absolute myelin yields from CNS taiep tissues peaked at similar to 2 months and then decreased until they reached a low but stable level. Myelin yield from the affected hemispheres expressed as a percentage of age-matched controls decreased continuously from 2 weeks until it reached a stable level of similar to 10-15%. The same was true for the spinal cords, but here the myelin yield reached a plateau at a slightly higher percentage of 20-25%. in comparison with control rats, isolated CNS myelin fractions from the affected rats had a greater content of high molecular weight proteins. Western blot analyses of CNS homogenates revealed that myelin basic protein (MBP), proteolipid protein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase were all present but decreased to levels generally consistent with the deficiencies of myelin. However myelin-associated glycoprotein (MAG) levels always were reduced much more than those of the other three myelin proteins, and at younger ages the apparent molecular weight for MAG was increased in the mutants. Western blot analyses of sciatic nerve homogenates showed that the levels of MBP, MAG, and Po were not significantly different in control and mutant animals. These results suggested an early hypomyelination of the CNS, with peak levels of myelin at 2 months, followed by a prolonged period of myelin loss, until a very low but stable myelin lever was reached. The consistently greater loss of MAG, in comparison with other CNS myelin proteins, is different from most other hypomyelinating mutants in which MAG is relatively preserved in comparison with the proteins of compact myelin. This might be due to microtubular abnormalities in the taiep mutant interfering with transport of myelin proteins and having the greatest effect on MAG because of its most distal location in the periaxonal oligodendroglial membranes. C1 NINCDS,CELLULAR & MOL NEUROBIOL LAB,NIH,BETHESDA,MD 20892. UNIV WISCONSIN,SCH VET MED,DEPT MED SCI,MADISON,WI 53706. RP Moller, JR (reprint author), NINCDS,DEMYELINATING DISORDERS UNIT,LMCN,NIH,49 CONVENT DR,MSC 4440,BETHESDA,MD 20892, USA. FU NINDS NIH HHS [NS 32361] NR 29 TC 16 Z9 17 U1 1 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 AUG PY 1997 VL 69 IS 2 BP 773 EP 779 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XL154 UT WOS:A1997XL15400037 PM 9231738 ER PT J AU Hirata, H Cadet, JL AF Hirata, H Cadet, JL TI p53-knockout mice are protected against the long-term effects of methamphetamine on dopaminergic terminals and cell bodies SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopamine systems; dopamine transporter; methamphetamine; neurotoxicity; p53; striatum; substantia nigra ID DISMUTASE TRANSGENIC MICE; MESSENGER-RNA EXPRESSION; CENTRAL-NERVOUS-SYSTEM; TUMOR-SUPPRESSOR P53; DNA-DAMAGING AGENTS; WILD-TYPE P53; STRIATAL DOPAMINE; IN-VIVO; INDUCED APOPTOSIS; OXIDATIVE STRESS AB p53-knockout mice provide a useful model to test the role of p53 in the neurotoxic effects of drugs in vivo. To test the involvement of p53 in methamphetamine (METH)-induced toxicity, wild-type mice, as well as heterozygous and homozygous p53-knockout male mice, were administered four injections of three different doses (2.5, 5.0, and 10.0 mg/kg) of the drug given at 2-h intervals within the space of 1 day. METH caused a marked dose-dependent loss of dopamine transporters in both the striatum and the nucleus accumbens of wild-type mice killed 2 weeks after drug administration. However, this METH-induced decrease in dopamine transporters was attenuated in both homozygous and heterozygous p53-knockout mice, with homozygous animals showing significantly greater protection. The possibility for p53 involvement in METH-induced toxicity was also supported by the observation that METH caused marked increases in p53-like immunoreactivity in the striata of wildtype mice and very little change in heterozygous p53-knockout mice, whereas no p53-like immunostaining was detected in the homozygous p53-knockout mice. Further support for p53 involvement was provided by the fact that METH treatment caused significant decreases in dopamine transporter mRNA and the number of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta and the ventral tegmental area of wild-type but not homozygous p53-knockout mice killed 2 weeks after cessation of METH administration. These results provide concordant evidence for a role of the tumor suppressor, p53, in the long-term deleterious effects of a drug acting on brain dopamine systems. C1 NIDA,MOL NEUROPSYCHIAT SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. NR 57 TC 84 Z9 86 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 AUG PY 1997 VL 69 IS 2 BP 780 EP 790 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XL154 UT WOS:A1997XL15400038 PM 9231739 ER PT J AU Metuzals, J Chang, D Hammar, K Reese, TS AF Metuzals, J Chang, D Hammar, K Reese, TS TI Organization of the cortical endoplasmic reticulum in the squid giant axon SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID SUBAXOLEMMAL CYTOSKELETON; TRANSMITTER RELEASE; NERVE-FIBER; CALCIUM; NETWORK; MICRODOMAINS; MEMBRANES; JUNCTION; PROTEINS; AXOLEMMA AB The organization of the cortical endoplasmic reticulum in the squid giant axon was investigated by rapid freeze and freeze-substitution electron microscopy, thereby eliminating the effects of fixatives on this potentially labile structure. Juvenile squid, which have thinner Schwann sheaths, were used in order to achieve freezing deep enough to include the entire axonal cortex. The smooth endoplasmic reticulum is composed of subaxolemmal and deeper cisternae, tubules, tethers and vesicles. The subaxolemmal cisternae make junctional contacts with the axolemma which are characterized by filamentous-granular bridging structures approximately 3 nm in diameter. The subaxolemmal junctions with the axolemma resemble the coupling junctions between the sarcoplasmic reticulum and the T-tubules in muscle. Reconstruction of short series of sections showed that a number of the elements of the endoplasmic reticulum were continuous but numerous separate vesicles were present as well. The morphology of endoplasmic reticulum as described here suggests that it is a highly dynamic entity as well as a Ca2+ sequestering organelle. C1 NINDS, NEUROBIOL LAB, NIH, BETHESDA, MD 20892 USA. MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. RP UNIV OTTAWA, FAC MED, DEPT PATHOL & LAB MED, OTTAWA, ON K1H 8M5, CANADA. FU NINDS NIH HHS [NS31256] NR 40 TC 16 Z9 16 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD AUG PY 1997 VL 26 IS 8 BP 529 EP 539 DI 10.1023/A:1015482407202 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA XY017 UT WOS:A1997XY01700002 PM 9350805 ER PT J AU Vergelli, M Kalbus, M Rojo, SC Hemmer, B Kalbacher, H Tranquill, L Beck, H McFarland, HF DeMars, R Long, EO Martin, R AF Vergelli, M Kalbus, M Rojo, SC Hemmer, B Kalbacher, H Tranquill, L Beck, H McFarland, HF DeMars, R Long, EO Martin, R TI T cell response to myelin basic protein in the context of the multiple sclerosis-associated HLA-DR15 haplotype: Peptide binding, immunodominance and effector functions of T cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE immunodominance; MBP; HLA binding; HLA-DR15; multiple sclerosis ID HLA-DR; HEALTHY-INDIVIDUALS; FINE SPECIFICITY; SELF-PEPTIDES; RECOGNITION; CLONES; MOLECULES; REQUIREMENTS; RESTRICTION; ANTIGENS AB In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131-159) are uniquely restricted by DR2a. The immunodominant middle epitope (81-99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell response. Overall, immunodominance in the MBP-specific T cell response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity. (C) 1997 Elsevier Science B.V. C1 NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. UNIV TUBINGEN,NEUROL KLIN,D-72076 TUBINGEN,GERMANY. NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. UNIV TUBINGEN,INST PHYSIOL CHEM,D-72076 TUBINGEN,GERMANY. UNIV WISCONSIN,GENET LAB,MADISON,WI 53706. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 30 TC 46 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD AUG PY 1997 VL 77 IS 2 BP 195 EP 203 DI 10.1016/S0165-5728(97)00075-1 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA XP905 UT WOS:A1997XP90500007 PM 9258250 ER PT J AU Zhang, L Peoples, RW Oz, M HarveyWhite, J Weight, FF Brauneis, U AF Zhang, L Peoples, RW Oz, M HarveyWhite, J Weight, FF Brauneis, U TI Potentiation of NMDA receptor-mediated responses by dynorphin at low extracellular glycine concentrations SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID D-ASPARTATE RECEPTOR; RAT-BRAIN; GUINEA-PIG; MODULATORY SITE; PYRAMIDAL CELLS; OPIOID-PEPTIDES; MOSSY FIBERS; SPINAL-CORD; HIPPOCAMPUS; RELEASE AB The effect of dynorphin A(1-13) on N-methyl-D-aspartate (NMDA)-activated currents was investigated in the presence of low extracellular glycine concentrations in Xenopus oocytes expressing recombinant heteromeric NMDA receptors and in cultured hippocampal neurons with the use of voltage-clamp techniques. At an extracellular added glycine concentration of 100 nM, dynorphin A(1-13) (10 mu M) greatly increased the amplitude of NMDA-activated currents for all heteromeric subunit combinations tested; on average, the potentiation was: epsilon 1/zeta 1, 3,377 +/- 1,416% (mean +/- SE); epsilon 2/zeta 1, 1,897 +/- 893%; epsilon 3/zeta 1, 4,356 +/- 846%; and epsilon 4/zeta 1, 1,783 +/- 503%. Potentiation of NMDA-activated current by dynorphin A(1-13) was concentration dependent between 0.1 and 10 mu M dynorphin A(1-13), with a half-maximal concentration value of 2.77 mu M and an apparent Hill coefficient of 2.53, for epsilon 2/zeta 1 subunits at 100 nM added extracellular glycine. Percentage potentiation by dynorphin A(1-13) was maximal at the lowest glycine concentrations tested (0.01 and 0.1 mu M), and decreased with increasing glycine concentration. No significant potentiation was observed at glycine concentrations >0.1 mu M for epsilon 1/zeta 1, epsilon 2/zeta 1, and epsilon 4/zeta 1 subunits, or at >1 mu M for epsilon 3/zeta 1 subunits. Potentiation of NMDA-activated currents by dynorphin A(1-13) was not inhibited by 1 mu M of the kappa-opioid receptor antagonist nor-binaltorphimine and potentiation was not observed with 10 mu M of the kappa-opioid receptor agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzene-acetamide. Potentiation of NMDA-activated current by dynorphin A(1-13) was inhibited by the glycine antagonist kynurenic acid (50 mu M). NMDA-activated current was also potentiated at low glycine concentrations by 10 mu M dynorphin A(2-13) or (3-13), both of which have a glycine as the first amino acid, but not by 10 mu M dynorphin A(4-13), which does not have glycine as an amino acid. In hippocampal neurons, 10 mu M dynorphin A(1-13) or (2-13) potentiated steady-state NMDA-activated current in the absence of added extracellular glycine. The extracellular free glycine concentration, determined by high-performance liquid chromatography, was between 26 and 36 nM for the bathing solution in presence or absence of 10 mu M dynorphin A(1-13), (2-13), (3-13), or (4-13), and did not differ significantly among these solutions. The observations are consistent with the potentiation of NMDA-activated current at low extracellular glycine concentrations resulting from an interaction of the glycine amino acids in dynorphin A(1-13) with the glycine coagonist site on the NMDA receptor. Because dynorphin A is an endogenous peptide that can be coreleased with glutamate at glutamatergic synapses, the potentiation of NMDA receptor-mediated responses could be an important physiological regulator of NMDA receptor function at these synapses. C1 NIAAA,CELLULAR & MOL NEUROBIOL LAB,NIH,ROCKVILLE,MD 20852. NINCDS,CLIN NEUROSCI BRANCH,NIH,ROCKVILLE,MD 20852. RI Oz, Murat/E-2148-2012 NR 48 TC 47 Z9 48 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1997 VL 78 IS 2 BP 582 EP 590 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XT273 UT WOS:A1997XT27300002 PM 9307096 ER PT J AU Zhu, Y Yakel, JL AF Zhu, Y Yakel, JL TI Modulation of Ca2+ currents by various G protein-coupled receptors in sympathetic neurons of male rat pelvic ganglia SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID BETA-GAMMA-SUBUNITS; CALCIUM CHANNELS; KINASE-C; N-TYPE; PERIPHERAL NEURONS; ADENYLATE-CYCLASE; PERTUSSIS TOXIN; INHIBITION; NEUROTRANSMITTERS; ACTIVATION AB The modulation of voltage-gated calcium (Ca2+) channels by various G protein-coupled receptor pathways was investigated in sympathetic neurons of the male rat major pelvic ganglion (MPG). Standard whole cell patch-clamp recording techniques were used to record Ca2+ currents from acutely dissociated neurons. The activation of muscarinic receptors, which uses a G protein pathway that was not blocked by either pertussis toxin (PTX) or cholera toxin (CTX), inhibited both N-type and L-type Ca2+ channels. The activation of alpha(2) noradrenergic receptors with the selective agonist UK14304, which used primarily a PTX-sensitive G protein pathway, inhibited only N-type Ca2+ channels. The activation of vasoactive intestinal polypeptide (VIP) receptors, which used a CTX-sensitive G protein pathway, also inhibited only N-type Ca2+ channels. UK14304 and VIP induced a bell-shaped inhibition of the Ca2+ current with a peak inhibition at around +10 mV and decreasing inhibition at more positive potentials. In contrast, the muscarine-induced Ca2+ current inhibition was not bell shaped and was more prominent at more positive potentials. Furthermore, a large depolarization, which relieved the current inhibition by UK14304 and VIP, did not relieve the inhibition by muscarine. Besides inhibiting the Ca2+ current, UK14304 and VIP also slowed the activation kinetics, an effect not seen with muscarine. Replacing external Ca2+ with Ba2+ and replacing internal ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid(EGTA) with high bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) completely blocked the inhibitory effect of muscarine. However, the inhibitory effects of both UK14304 and VIP were unaffected under these conditions. Surprisingly, the facilitation of the Ca2+ current was eliminated under these strong calcium-buffering conditions. The activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (PMA) increases the amplitude of the Ca2+ current, diminishes facilitation, and reduces the inhibition of this current by UK14304 and VIP. However, PKC activation did not reduce the muscarine-induced Ca2+ current inhibition. in summary, our data suggest that muscarine uses a mechanism different from UK14304 and VIP to modulate the N-type Ca2+ channels in sympathetic neurons of the MPG. Although VIP and UK14304 use different G protein pathways, these two different pathways most likely converge downstream to compete for the same target site on the N-type Ca2+ channels. C1 NIEHS,LAB SIGNAL TRANSDUCT,RES TRIANGLE PK,NC 27709. NR 38 TC 28 Z9 28 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 AUG PY 1997 VL 78 IS 2 BP 780 EP 789 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XT273 UT WOS:A1997XT27300018 PM 9307112 ER PT J AU Deiber, MP Wise, SP Honda, M Catalan, MJ Grafman, J Hallett, M AF Deiber, MP Wise, SP Honda, M Catalan, MJ Grafman, J Hallett, M TI Frontal and parietal networks for conditional motor-learning: A positron emission tomography study SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MONKEYS MACACA-FASCICULARIS; SUPPLEMENTARY EYE FIELD; CEREBRAL BLOOD-FLOW; PREMOTOR CORTEX; PREFRONTAL CORTEX; FUNCTIONAL-ANATOMY; EPISODIC MEMORY; CORTICAL AREAS; WORKING-MEMORY; CORTICOSPINAL PROJECTIONS AB Studies on nonhuman primates show that the premotor (PM) and prefrontal (PF) areas are necessary for the arbitrary mapping of a set of stimuli onto a set of responses. However, positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) in human subjects have failed to reveal the predicted rCBF changes during such behavior. We therefore studied rCBF while subjects learned two arbitrary mapping tasks. In the conditional motor task, visual stimuli instructed which of four directions to move a joystick (with the right, dominant hand). In the evaluation task, subjects moved the joystick in a predetermined direction to report whether an arrow pointed in the direction associated with a given stimulus. For both tasks there were three rules: for the nonspatial rule, the pattern within each stimulus determined the correct direction; for the spatial rule, the location of the stimulus did so; and for the fixed-response rule, movement direction was constant regardless of the pattern or its location. For the nonspatial rule, performance of the evaluation task led to a learning-related increase in rCBF in a caudal and ventral part of the premotor cortex (PMvc, area 6), bilaterally, as well as in the putamen and a cingulate motor area (CM, area 24) of the left hemisphere. Decreases in rCBF were observed in several areas: the left ventro-orbital prefrontal cortex (PFv, area 47/12), the left lateral cerebellar hemisphere, and, in the right hemisphere, a dorsal and rostral aspect of PM (PMdr, area 6), dorsal PF (PFd, area 9), and the posterior parietal cortex (area 39/40). During performance of the conditional motor task, there was only a decrease in the parietal area. For the spatial rule, no rCBF change reached significance for the evaluation task, but in the conditional motor task, a ventral and rostral premotor region (PMvr, area 6), the dorsolateral prefrontal cortex (PFdl, area 46), and the posterior parietal cortex (area 39/40) showed decreasing rCBF during learning, all in the right hemisphere. These data confirm the predicted rCBF changes in premotor and prefrontal areas during arbitrary mapping tasks and suggest that a broad frontoparietal network may show decreased synaptic activity as arbitrary rules become more familiar. C1 NINCDS,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. CTR EXPLORAT & RECH MED EMISS POSITRONS,INSERM,F-69003 LYON,FRANCE. RP Deiber, MP (reprint author), NIMH,LAB SYST NEUROSCI,POB 608,POOLESVILLE,MD 20837, USA. RI Deiber, Marie-Pierre/M-5949-2014; OI Grafman, Jordan H./0000-0001-8645-4457 NR 100 TC 147 Z9 148 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1997 VL 78 IS 2 BP 977 EP 991 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XT273 UT WOS:A1997XT27300034 PM 9307128 ER PT J AU Suzuki, WA Miller, EK Desimone, R AF Suzuki, WA Miller, EK Desimone, R TI Object and place memory in the macaque entorhinal cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INFERIOR TEMPORAL CORTEX; SHORT-TERM-MEMORY; VISUAL RECOGNITION MEMORY; POSTERIOR PARIETAL CORTEX; HIPPOCAMPAL-FORMATION; PARAHIPPOCAMPAL CORTICES; NEURONAL-ACTIVITY; SPATIAL LOCATION; RHESUS-MONKEY; FORNIX TRANSECTION AB Lesions of the entorhinal cortex in humans, monkeys, and rats impair memory for a variety of kinds of information, including memory for objects and places. To begin to understand the contribution of entorhinal cells to different forms of memory, responses of entorhinal cells were recorded as monkeys performed either an object or place memory task. The object memory task was a variation of delayed matching to sample. A sample picture was presented at the start of the trial, followed by a variable sequence of zero to four test pictures, ending with a repetition of the sample (i.e., a match). The place memory task was a variation of delayed matching to place. In this task, a cue stimulus was presented at a variable sequence of one to four ''places'' on a computer screen, ending with a repetition of one of the previously shown places (i.e., a match). For both tasks, the animals were rewarded for releasing a bar to the match. To solve these tasks, the monkey must 1) discriminate the stimuli, 2) maintain a memory of the appropriate stimuli during the course of the trial, and 3) evaluate whether a test stimulus matches previously presented stimuli. The responses of entorhinal cortex neurons were consistent with a role in all three of these processes in both tasks. We found that 47% and 55% of the visually responsive entorhinal cells responded selectively to the different objects or places presented during the object or place task; respectively. Similar to previous findings in prefrontal but not perirhinal cortex on the object task, some entorhinal cells had sample-specific delay activity that was maintained throughout all of the delay intervals in the sequence. For the place task, some cells had location-specific maintained activity in the delay immediately following a specific cue location. In addition, 59% and 22% of the visually responsive cells recorded during the object and place task, respectively, responded differently to the test stimuli according to whether they were matching or nonmatching to the stimuli held in memory. Responses of some cells were enhanced to matching stimuli, whereas others were suppressed. This suppression or enhancement typically occurred well before the animals' behavioral response, suggesting that this infor mation could be used to perform the task. These results indicate that entorhinal cells receive sensory information about both objects and spatial locations and that their activity carries information about objects and locations held in short-term memory. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. RP Suzuki, WA (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,49 CONVENT DR,MSC 4415,BETHESDA,MD 20892, USA. NR 81 TC 250 Z9 253 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1997 VL 78 IS 2 BP 1062 EP 1081 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XT273 UT WOS:A1997XT27300041 PM 9307135 ER PT J AU Quaia, C Optican, LM AF Quaia, C Optican, LM TI Model with distributed vectorial premotor bursters accounts for the component stretching of oblique saccades SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MONKEY SUPERIOR COLLICULUS; ALERT SQUIRREL-MONKEY; NEURAL-NETWORK MODEL; EYE-MOVEMENTS; QUANTITATIVE-ANALYSIS; ON-DIRECTIONS; RHESUS-MONKEY; NEURONS; GENERATION; STIMULATION AB During oblique saccades, the durations of the horizontal and vertical components are stretched until they are approximately equal. Models of the saccadic system have been proposed that provide a mechanism for that stretching. However, they fail to simulate the pattern of activity recorded from premotor medium lead burst neurons (MLBNs) in the brain stem. A new model of the saccadic system is proposed that accounts for both the component stretching of oblique movements and the pattern of activity recorded in MLBNs. MLBNs that project to horizontal (or vertical) motoneurons actually have a wide span of on-directions (the direction associated with the largest discharge) around the cardinal direction. We infer from the wide span of their on-directions that, at the level of individual MLBNs, the vectorial signal present in spatially organized structures (e.g., the superior colliculus) is not decomposed into the separate horizontal and vertical components represented by the motoneurons. Nonetheless, all prior models of the saccadic system have decomposed the vectorial premotor command into horizontal and vertical commands at the level of the MLBNs. That decomposition was explicit, because individual MLBNs, with a sine-or cosine-shaped directional tuning curve, were used. We propose here that the decomposition into horizontal and vertical commands is carried out only at the level of the motoneurons. This decomposition is implicit, because no single MLBN encodes the horizontal or vertical command; the command only exists implicitly in the activity of the population of MLBNs. The new vectorial burster model correctly simulates the pattern of activity recorded in primate MLBNs, and the components of its oblique saccades are stretched. Two mechanisms contribute to this stretching: the distribution of MLBN tuning curves and the inhibition exerted by the contralateral population of MLBNs. In contrast, feedback control of the saccade contributes negligibly to the stretching. Even though the vectorial burster model predicts a component stretching, it is not constrained to produce perfectly straight oblique saccades because no trajectory control is implemented. The amount of curvature depends on the similarity of the horizontal and vertical systems (both neural and mechanical). In this model, stretching is inter interpreted simply as a side effect of the properties of the MLBNs' tuning curves. The distributed MLBNs of the vectorial burster model forces the general organization of the saccadic system to be reconsidered. We propose that a distributed architecture in which several different neural systems cooperate is needed. C1 NEI, NIH, SENSORIMOTOR RES LAB, BETHESDA, MD 20892 USA. NR 58 TC 22 Z9 22 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1997 VL 78 IS 2 BP 1120 EP 1134 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XT273 UT WOS:A1997XT27300045 PM 9307139 ER PT J AU Zhu, Y Yakel, JL AF Zhu, Y Yakel, JL TI Calcineurin modulates G protein-mediated inhibition of N-type calcium channels in rat sympathetic neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID AUTOINHIBITORY DOMAIN; KINASE-C; RELEASE; GLUTAMATE; GANGLION AB The modulation of N-type voltage-gated calcium (Ca2+) channels by G protein-coupled receptors was investigated in sympathetic neurons of the male rat major pelvic ganglion (MPG) with the use of whole cell patch-clamp recording techniques from acutely dissociated neurons. By inhibiting calcineurin, a Ca2+/calmodulin-regulated protein phosphatase, the alpha(2) noradrenergic and somatostatin receptor-induced inhibition of these N-type Ca2+ channels was greatly reduced. Both of these receptor pathways utilize a pertussis toxin-sensitive G protein (G(PTX)) The guanosine 5'-o-(3-thiotriphosphate) (GTP gamma S)-induced decrease in the amplitude and activation kinetics of Ca2+ currents, an effect that was similar to the activation of G(PTX)-coupled receptors, also was reduced by the inhibition of calcineurin. Calcineurin does not regulate the muscarinic receptor-induced inhibition of the N-type Ca2+ channels, a pathway that utilizes a different G protein in the MPG neurons. Thus calcineurin appears to selectively regulate the coupling between the G(PTX) and the Ca2+ channel. C1 NIEHS,SIGNAL TRANSDUCT LAB,RES TRIANGLE PK,NC 27709. NR 17 TC 30 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1997 VL 78 IS 2 BP 1161 EP 1165 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XT273 UT WOS:A1997XT27300050 PM 9307144 ER PT J AU Chen, LL Wise, SP AF Chen, LL Wise, SP TI Conditional oculomotor learning: Population vectors in the supplementary eye field SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NEURONAL POPULATION; ASSOCIATIONS; ACQUISITION; MOVEMENTS AB We have shown previously that the activity levels and preferred directions of supplementary eye field neurons change as monkeys learn to associate nonspatial visual information with a saccade (or the spatial target of that saccade). The present report describes changes in neuronal population vectors (PV) during such learning. PVs based on neuronal activity shortly before and after saccades predicted movement direction poorly in the earliest stage of learning, but as monkeys mastered novel stimulus-response mappings, PV accuracy and magnitude increased significantly. C1 NIMH,SYST NEUROSCI LAB,POOLESVILLE,MD 20837. NR 17 TC 34 Z9 34 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1997 VL 78 IS 2 BP 1166 EP 1169 PG 4 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XT273 UT WOS:A1997XT27300051 PM 9307145 ER PT J AU Sekiguchi, M Fleck, MW Mayer, ML Takeo, J Chiba, Y Yamashita, S Wada, K AF Sekiguchi, M Fleck, MW Mayer, ML Takeo, J Chiba, Y Yamashita, S Wada, K TI A novel allosteric potentiator of AMPA receptors: 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate receptors; AMPA; desensitization; alternative splicing; flip and flop; allosteric modulation ID EXCITATORY SYNAPTIC CURRENTS; GLUTAMATE-OPERATED CHANNELS; NOOTROPIC DRUG ANIRACETAM; HIPPOCAMPAL-NEURONS; STRUCTURAL DETERMINANTS; SULFONAMIDE DERIVATIVES; FUNCTIONAL EXPRESSION; KAINATE RECEPTORS; ACID RECEPTOR; TIME-COURSE AB We report that a novel sulfonylamino compound, 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide (PEPA), selectively potentiates glutamate receptors of the AMPA subtype. PEPA (1-200 mu M) dose dependently potentiated glutamate-evoked currents in Xenopus oocytes expressing AMPA (GluRA-GluRD), but not kainate (GluR6 and GluR6+KA2) or NMDA(zeta 1 + epsilon 1-epsilon 4), receptor subunits. PEPA was effective at micromolar concentrations and, in contrast to the action of cyclothiazide, preferentially modulated AMPA receptor flop isoforms. At 200 mu M, PEPA potentiated glutamate responses by 50-fold in oocytes expressing GluRC(flop) (EC50 similar to 50 mu M) versus only threefold for GluRC(flip); a similar preference for flop isoforms was observed far other AMPA receptor subunits. Dose-response analysis for GluRC(flop) revealed that 100 mu M PEPA produced a sevenfold increase in AMPA receptor affinity for glutamate. PEPA produced considerably weaker potentiation of kainate-evoked than glutamate-evoked currents, suggesting modulation of the process of receptor desensitization. In human embryonic kidney 293 cells transfected with AMPA receptor subunits, PEPA either abolished or markedly slowed the rate of onset of desensitization and potentiated steady-state equilibrium currents evoked by glutamate with subunit (GruRC greater than or equal to GluRD > GluRA) and splice-variant (flop > flip) selectivity similar to that observed in oocytes. Our results show that PEPA is a novel, flop-preferring allosteric modulator of AMPA receptor desensitization at least 100 times more potent than aniracetam. C1 NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NIH,BETHESDA,MD 20892. NIPPON SUISAN KAISHA LTD,CENT RES LAB,HACHIOJI,TOKYO 192,JAPAN. RP Sekiguchi, M (reprint author), NATL CTR NEUROL & PSYCHIAT,NATL INST NEUROSCI,DEPT DEGENERAT NEUROL DIS,4-1-1 OGAWAHIGASHI,KODAIRA,TOKYO 187,JAPAN. RI Mayer, Mark/H-5500-2013 NR 50 TC 78 Z9 79 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1997 VL 17 IS 15 BP 5760 EP 5771 PG 12 WC Neurosciences SC Neurosciences & Neurology GA XU918 UT WOS:A1997XU91800010 PM 9221774 ER PT J AU Chang, JHT Milligan, S Li, YY Chew, CE Wiggs, J Copeland, NG Jenkins, NA Campochiaro, PA Hyde, DR Zack, DJ AF Chang, JHT Milligan, S Li, YY Chew, CE Wiggs, J Copeland, NG Jenkins, NA Campochiaro, PA Hyde, DR Zack, DJ TI Mammalian homolog of Drosophila retinal degeneration B rescues the mutant fly phenotype SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retina; retinal degeneration; phosphatidylinositol transfer protein; photoreceptors; phototransduction; retinal degeneration B ID PHOSPHATIDYLINOSITOL TRANSFER PROTEIN; VITELLIFORM MACULAR DYSTROPHY; PHOTORECEPTOR CELLS; GENETIC-LINKAGE; PHOSPHOLIPASE-C; RDGB GENE; SUBRHABDOMERIC CISTERNAE; RETINITIS-PIGMENTOSA; MELANOGASTER; RHODOPSIN AB Mutations in the Drosophila rdgB gene, which encodes a transmembrane phosphatidylinositol transfer protein (PITP), cause a light-enhanced retinal degeneration. Cloning of mammalian rdgB orthologs (mrdgB) reveal predicted proteins that are 39% identical to rdgB, with highest homology in the N-terminal PITP domain (62%) and in a region near the C terminus (65%). The human mrdgB gene spans similar to 12 kb and maps to 11q13.1, a locus where several retinal diseases have also been mapped. Murine mrdgB maps to a syntenic region on the proximal region of chromosome 19. MrdgB is specifically expressed in the retina and brain. In the retina, MrdgB protein is localized to photoreceptor inner segments and the outer and inner plexiform layers. Expression of murine mrdgB in mutant flies fully rescues both the rdgB-dependent retinal degeneration and abnormal electroretinogram. These results suggest the existence of similarities between the invertebrate and mammalian retina that were not previously appreciated and also identify mrdgB as a candidate gene for retinal diseases that map to 11q13.1. C1 JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21287. UNIV NOTRE DAME,DEPT BIOL SCI,NOTRE DAME,IN 46556. TUFTS UNIV,SCH MED,NEW ENGLAND EYE CTR,BOSTON,MA 02111. NCI,FREDERICK CANC RES & DEV CTR,ABL,MAMMALIAN GENET LAB,FREDERICK,MD 21702. OI Zack, Don/0000-0002-7966-1973 FU NEI NIH HHS [EY05951, EY08058, EY09679] NR 56 TC 57 Z9 58 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1997 VL 17 IS 15 BP 5881 EP 5890 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XU918 UT WOS:A1997XU91800021 PM 9221785 ER PT J AU Wang, XB Funada, M Imai, Y Revay, RS Ujike, H Vandenbergh, DJ Uhl, GR AF Wang, XB Funada, M Imai, Y Revay, RS Ujike, H Vandenbergh, DJ Uhl, GR TI rG beta(1): A psychostimulant-regulated gene essential for establishing cocaine sensitization SO JOURNAL OF NEUROSCIENCE LA English DT Article DE PCR differential display; amphetamine; cocaine; G-protein; sensitization; gene regulation; addiction ID BETA-GAMMA-SUBUNITS; VENTRAL TEGMENTAL AREA; HETEROTRIMERIC G-PROTEINS; BEHAVIORAL SENSITIZATION; NUCLEUS-ACCUMBENS; PHOSPHOLIPASE-C; POTASSIUM CHANNEL; CHRONIC MORPHINE; KINASE PATHWAY; DRUG-ADDICTION AB Repeated doses of cocaine or amphetamine lead to longlasting behavioral manifestations that include enhanced responses termed sensitization. Although biochemical mechanisms that underlie these manifestations currently remain largely unknown, new protein synthesis has been implicated in several of these neuroadaptive processes. To seek candidate biochemical mechanisms for these drug-induced neuroplastic behavioral responses, we have used an approach termed subtracted differential display (SDD) to identify genes whose expression is regulated by these psychostimulants. rG beta(1), is one of the SDD products that encodes a rat G-protein beta subunit. rG beta(1) expression is upregulated by cocaine or amphetamine treatments in neurons of the nucleus accumbens shell region, a major center for psychostimulant effects in locomotor control and behavioral reward. Antisense oligonucleotide treatments that attenuate rG beta(1) expression in regions including the nucleus accumbens abolish the development of behavioral sensitization when they are administrated during the repeated cocaine exposures that establish sensitization. These treatments fail to alter acute behavioral responses to cocaine, and they do not block the expression of cocaine sensitization when it is established before oligonucleotide administrations. Full, regulated rG beta(1) expression is a biochemical component essential to the establishment of a key consequence of repeated cocaine administrations, sensitization. C1 NIDA,MOL NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NR 40 TC 43 Z9 44 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1997 VL 17 IS 15 BP 5993 EP 6000 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XU918 UT WOS:A1997XU91800031 PM 9221795 ER PT J AU Malkova, L Gaffan, D Murray, EA AF Malkova, L Gaffan, D Murray, EA TI Excitotoxic lesions of the amygdala fail to produce impairment in visual learning for auditory secondary reinforcement but interfere with reinforcer devaluation effects in rhesus monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amygdala; ibotenic acid; visual discrimination; auditory; secondary reinforcement; reinforcer devaluation; rhesus monkey ID STIMULUS-REWARD ASSOCIATIONS; CONDITIONED PLACE PREFERENCE; CORTICAL AFFERENTS; CORTEX; MEMORY; DISCONNECTION; ABLATION; SYSTEMS; NUCLEUS; FOOD AB Aspiration lesions of the amygdala were found previously to produce a severe impairment in visual discrimination learning for auditory secondary reinforcement in rhesus monkeys (Gaffan and Harrison, 1987), To determine whether excitotoxic amygdala lesions would also produce this effect, we trained four naive rhesus monkeys on the same task, The monkeys were required to learn 40 new visual discrimination problems per session in a situation in which visual choices were guided by an auditory secondary reinforcer that had been previously associated with food reward. Bilateral excitotoxic lesions of the amygdala had no effect on the rate of learning visual discrimination problems for auditory secondary reinforcement. We also tested the amygdalectomized monkeys on a reinforcer devaluation task and compared their performance with a group of three normal monkeys. The monkeys first learned to discriminate 60 pairs of objects, baited with two different food rewards. Each of the food rewards was then devalued by selective satiation in two separate experimental sessions, Normal controls tended to avoid displacing objects that covered the devalued food to a significantly greater degree than did the amygdalectomized monkeys, indicating that the excitotoxic amygdala damage interfered with reinforcer devaluation effects, Our results are consistent with the idea that the amygdala is necessary for learning the association between stimuli and the value of particular food rewards; however, the amygdala is not necessary for maintaining the value of secondary reinforcers, once they have been learned. C1 NIMH,NEUROPSYCHOL LAB,NIH,BETHESDA,MD 20892. UNIV OXFORD,DEPT EXPT PSYCHOL,OXFORD OX1 3UD,ENGLAND. OI Murray, Elisabeth/0000-0003-1450-1642 NR 33 TC 212 Z9 213 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1997 VL 17 IS 15 BP 6011 EP 6020 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XU918 UT WOS:A1997XU91800033 PM 9221797 ER PT J AU Luna, JD Chan, CC Derevjanik, NL Mahlow, J Chiu, C Peng, B Tobe, T Campochiaro, PA Vinores, SA AF Luna, JD Chan, CC Derevjanik, NL Mahlow, J Chiu, C Peng, B Tobe, T Campochiaro, PA Vinores, SA TI Blood-retinal barrier (BRB) breakdown in experimental autoimmune uveoretinitis: Comparison with vascular endothelial growth factor, tumor necrosis factor alpha, and interleukin-1 beta-mediated breakdown SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE autoimmune disease; growth factors; inflammatory mediators; cyclosporine; dexamethasone; thromboxane synthetase; vesicular transport ID ENDOTOXIN-INDUCED UVEITIS; PERMEABILITY FACTOR; LEWIS RATS; INTRAOCULAR INFLAMMATION; IMMUNOHISTOCHEMICAL LOCALIZATION; ULTRASTRUCTURAL PATHOLOGY; FACTOR EXPRESSION; ALDOSE REDUCTASE; GENE-EXPRESSION; TIGHT JUNCTIONS AB Experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by immunization with S-antigen is a model of human uveitis. By using immunocytochemical staining for albumin, relatively minor blood-retinal barrier (BRB) breakdown was initially shown in the peripheral retina 8 days after immunization and in the posterior retina by 10 days, Albumin extravasation appeared to occur by opening of the retinal vascular endothelial (RVE) and the retinal pigmented epithelial (RPE) tight junctions, by transendothelial vesicular transport, and by permeating damaged RVE cells. Each of three anti-inflammatory agents reduced or delayed autoimmune-mediated cell destruction but did not eliminate any particular route of extravasation. Vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF alpha), and interleukin-1(beta) (IL-1(beta)) are intimately associated with the development of EAU and are capable of causing BRB dysfunction, A high percentage of RVE tight junctions appeared open ultrastructurally after intravitreal injection of VEGF (26.7%), TNF alpha (35.6%), or IL-1(beta) (22.1%) compared with saline-injected control (11.4%) or normal, untreated rabbits (4.1%), Heat treatment abolished the effect of IL-1(beta) an the BRB but only partially reduced the effect of VEGF. By 24 hr after injection, the effect of TNF alpha had reversed, but: that of IL-1(beta) had not; VEGF-mediated BRB dysfunction was partially reversible, In addition, albumin-filled vesicle-like structures were seen in the RVE cytoplasm following treatment with each mediator. This study shows that VEGF, TNF alpha, and IL-1(beta) each cause BRB breakdown by opening tight junctions between RVE cells and possibly by increasing transendothelial vesicular transport. Each of these agents may contribute to BRB breakdown in EAU and in patients with uveitis, (C) 1997 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,WILMER OPHTHALMOL INST,BALTIMORE,MD 21287. NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. FU NEI NIH HHS [EY05951, EY10017] NR 83 TC 97 Z9 103 U1 1 U2 5 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 AUG 1 PY 1997 VL 49 IS 3 BP 268 EP 280 DI 10.1002/(SICI)1097-4547(19970801)49:3<268::AID-JNR2>3.0.CO;2-A PG 13 WC Neurosciences SC Neurosciences & Neurology GA XN887 UT WOS:A1997XN88700002 PM 9260738 ER PT J AU Goodrum, JF Pentchev, PG AF Goodrum, JF Pentchev, PG TI Cholesterol reutilization during myelination of regenerating PNS axons is impaired in Niemann-Pick disease type C mice SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE cholesterol; lipidosis; neuropathy; nerve regeneration; remyelination ID PERIPHERAL-NERVE; LIPIDS AB Niemann-Pick C (NPC) disease is an autosomal recessive lipidosis characterized by lysosomal accumulations of unesterified cholesterol. Cultured NPC cells exhibit a defect in the intracellular trafficking of LDL-derived cholesterol that leads to lysosomal accumulations of unesterified cholesterol. We found in a preliminary study that the myelination of regenerating axons was retarded in the NPC mouse following sciatic nerve crush, Because lipoprotein-mediated cholesterol transport is involved in myelination during nerve regeneration, we investigated whether this cholesterol reutilization pathway was perturbed in the NPC mouse, Mice received intraneural injections of [H-3]acetate to label myelin cholesterol, and 2 weeks later the injected nerves were crushed above the injection site, Four weeks after crush, the nerves were examined by electron microscopic autoradiography, In normal mice, regeneration was well advanced, with thick myelin sheaths surrounding the regenerated axons and very little myelin debris remaining, The new myelin sheaths were well labeled, indicative of efficient cholesterol reutilization, In NPC mice, the new myelin sheaths were thinner and contained little label, indicative of retarded regeneration and little or no cholesterol reutilization, These data suggest the possibility of a causal link between compromised cholesterol reutilization and delayed or slowed regeneration of myelin sheaths, (C) 1997 Wiley-Liss, Inc. C1 UNIV N CAROLINA, N CAROLINA NEUROSCI CTR, CHAPEL HILL, NC 27599 USA. NINCDS, MOL & CELLULAR PATHOPHYSIOL SECT, DEV & METAB NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Goodrum, JF (reprint author), UNIV N CAROLINA, DEPT PATHOL & LAB MED, CB 7525, 409 BRINKHOUS BULLITT BLDG, CHAPEL HILL, NC 27599 USA. FU NICHD NIH HHS [HD-03110]; NIEHS NIH HHS [ES-01104] NR 9 TC 25 Z9 25 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 1 PY 1997 VL 49 IS 3 BP 389 EP 392 DI 10.1002/(SICI)1097-4547(19970801)49:3<389::AID-JNR14>3.0.CO;2-V PG 4 WC Neurosciences SC Neurosciences & Neurology GA XN887 UT WOS:A1997XN88700014 PM 9260750 ER PT J AU Pluta, RM Boock, RJ Afshar, JK Clouse, K Bacic, M Ehrenreich, H Oldfield, EH AF Pluta, RM Boock, RJ Afshar, JK Clouse, K Bacic, M Ehrenreich, H Oldfield, EH TI Source and cause of endothelin-1 release into cerebrospinal fluid after subarachnoid hemorrhage SO JOURNAL OF NEUROSURGERY LA English DT Article DE endothelin; vasospasm; subarachnoid hemorrhage; cerebral ischemia; cynomolgus monkey ID ISCHEMIC NEUROLOGICAL DEFICITS; ET(A) RECEPTOR ANTAGONIST; SMOOTH-MUSCLE CELLS; CEREBRAL VASOSPASM; NITRIC-OXIDE; GLIAL-CELLS; BLOOD-FLOW; HEMOGLOBIN; PLASMA; EXPRESSION AB Despite years of research, delayed cerebral vasospasm remains a serious complication of subarachnoid hemorrhage (SAH). Recently, it has been proposed that endothelin-1 (ET-1) mediates vasospasm. The authors examined this hypothesis in a series of experiments. In a primate model of SAH, serial ET-1 levels were measured in samples from the perivascular space by using a microdialysis technique and in cerebrospinal fluid (CSF) and plasma during the development and resolution of delayed vasospasm. To determine whether elevated ET-1 production was a direct cause of vasospasm or acted secondary to ischemia, the authors also measured ET-1 levels in plasma and CSF after transient cerebral ischemia. To elucidate the source of ET-1, they measured its production in cultures of endothelial cells and astrocytes exposed to oxyhemoglobin (10 mu M), methemoglobin (10 mu M), or hypoxia (11% oxygen). There was no correlation between the perivascular levels of ET-1 and the development of vasospasm or its resolution. Cerebrospinal fluid and plasma levels of ET-1 were not affected by vasospasm (CSF ET-1 levels were 9.3 +/- 2.2 pg/ml and ET-1 plasma levels were 1.2 +/- 0.6 pg/ml) before SAH and remained unchanged when vasospasm developed (7.1 +/- 1.7 pg/ml in CSF and 2.7 +/- 1.5 pg/ml in plasma). Transient cerebral ischemia evoked an increase of ET-1 levels in CSF (1 +/- 0.4 pg/ml at the occlusion vs. 3.1 +/- 0.6 pg/ml 4 hours after reperfusion; p < 0.05), which returned to normal (0.7 +/- 0.3 pg/ml) after 24 hours. Endothelial cells and astrocytes in culture showed inhibition of ET-1 production 6 hours after exposure to hemoglobins. Hypoxia inhibited ET-1 release by endothelial cells at 24 hours (6.4 +/- 0.8 pg/ml vs. 0.1 +/- 0.1 pg/ml, control vs, hypoxic endothelial cells; p < 0.05) and at 48 hours (6.4 +/- 0.6 pg/ml vs. 0 +/- 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05), but in astrocytes hypoxia induced an increase of ET-1 at 6 hours (1.5 +/- 0.6 vs. 6.4 +/- 1.1 pg/ml, control vs. hypoxic astrocytes; p < 0.05). Endothelin-1 is released from astrocytes, but not endothelial cells, during hypoxia and is released from the brain after transient ischemia. There is no relationship between ET-1 and vasospasm in vivo or between ET-1 and oxyhemoglobin, a putative agent of vasospasm, in vitro. The increase in ET-1 levels in CSF after SAH from a ruptured intracranial aneurysm appears to be the result of cerebral ischemia rather than reflecting the cause of cerebral vasospasm. C1 NINCDS,SURG NEUROL BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD. UNIV GOTTINGEN,DEPT NEUROL & PSYCHIAT,D-3400 GOTTINGEN,GERMANY. NR 58 TC 111 Z9 114 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 1997 VL 87 IS 2 BP 287 EP 293 DI 10.3171/jns.1997.87.2.0287 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA XN706 UT WOS:A1997XN70600020 PM 9254095 ER PT J AU Ensoli, F Wang, H Fiorelli, V Zeichner, SL DeCristofaro, MR Luzi, G Thiele, CJ AF Ensoli, F Wang, H Fiorelli, V Zeichner, SL DeCristofaro, MR Luzi, G Thiele, CJ TI HIV-1 infection and the developing nervous system: lineage-specific regulation of viral gene expression and replication in distinct neuronal precursors SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE gene regulation; HIV-1; CNS; development cell cycle; pediatric AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; IMMUNE-DEFICIENCY SYNDROME; T-CELLS; TRANSCRIPTIONAL REGULATION; BLASTOMA CELLS; HTLV-III; AIDS; CHILDREN; TYPE-1 AB Neurologic abnormalities are common in HIV-1 infected patients and often represent the dominant clinical manifestation of pediatric AIDS. Although the neurological dysfunction has been directly related to CNS invasion by HIV-1, the pathogenesis of neurologic disorders remains unclear. Microglia and macrophages are major HIV-1 targets in the brain, whereas HIV-1 infected neurons or glial cells have been rarely reported. This suggests that indirect mechanisms may account for the severe neuronal damage observed in these patients. Nevertheless, immature, mitotically active neuronal and glial cells, which are present during fetal development, are susceptible to HIV-1 infection and replication in vitro, suggesting that HIV-1 infection during organ development may present unique features. To better characterize virus-host cells interactions in the developing CNS, we have examined the susceptibility of embryologically and biochemically distinct neuronal cell lines to HIV-1 infection. Here we show that mitotically active, immature neurons of distinct lineages, have different susceptibilities to HIV-1 infection and replication and different abilities to support viral gene expression. Mutational analysis of HIV-1 LTR reveals that a region of the viral promoter between nucleotide -255 to -166 is responsible for most quantitative and qualitative differences in viral transactivation among different neuroblasts. This suggests that specific regions of the viral promoter and cellular factors, either Lineage-or differentiation-dependent, which bind to those regions, may contribute to control the levels of virus replication and possibly restrict the viral tropism in the developing brain. This may contribute to the establishment of a virus reservoir in the immature CNS and participate by either direct or indirect mechanisms to the severity of the AIDS-related pediatric neurological dysfunction. C1 NCI,HIV & AIDS MALIGNANCIES BRANCH,DCS,NIH,BETHESDA,MD 20892. UNIV ROMA LA SAPIENZA,DEPT ALLERGY & CLIN IMMUNOL,I-00185 ROME,ITALY. RP Ensoli, F (reprint author), NCI,CELL & MOL BIOL PEDIAT ONCOL BRANCH,DCS,NIH,BETHESDA,MD 20892, USA. NR 52 TC 23 Z9 23 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 1997 VL 3 IS 4 BP 290 EP 298 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA XT808 UT WOS:A1997XT80800006 PM 9291237 ER PT J AU Horti, A Scheffel, U Stathis, M Finley, P Ravert, HT London, ED Dannals, RF AF Horti, A Scheffel, U Stathis, M Finley, P Ravert, HT London, ED Dannals, RF TI Fluorine-18-FPH for PET imaging of nicotinic acetylcholine receptors SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE nicotinic acetylcholine receptor; brain imaging; PET ID POSITRON EMISSION TOMOGRAPHY; BINDING-SITES; POISON FROG; CHOLINERGIC RECEPTORS; H-3 EPIBATIDINE; BRAIN; INVIVO; RAT; ALKALOIDS; DIVERSITY AB Visualization of central nicotinic acetylcholine receptors (nAChRs) with modern PET or SPECT imaging techniques has been hampered by the tack of a radioligand with suitable in vivo binding characteristics (i.e., high target-to-nontarget ratios and kinetics appropriate for the half-life of the tracer and imaging modality used). This paper describes in vivo binding, kinetics and pharmacology of a highly potent F-18-labeled analog of epibatidine, (+/-)-exo-2-(2-[18 F]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane ([F-18]FPH), in the mouse brain with the view towards application of this tracer for PET imaging of nAChR in human brain. Methods: Fluorine-18-FPH was administered intravenously to mice, and time-activity curves were determined for several regions in the brain and other organs. Saturation and pharmacology of [F-18]FPH binding was demonstrated in vivo by preinjecting unlabeled FPH or other drugs with known pharmacological action before [F-18]FPH was injected. The effect of the drugs on [F-18]FPH accumulation was evaluated. Results: [F-18]FPH was rapidly incorporated into the mouse brain; peak activity (2.4% of the injected dose) was measured at 5 min after intravenous administration, followed by washout to 1.1% injected dose (ID) at 60 min. Highest concentrations of F-18 occurred at 15 min in areas known to contain high densities of nAChR {e.g., thalamus [9.7% of injected dose per gram tissue (ID/g)] and superior colliculus (8.3% ID/g)}. Accumulation of the F-18 tracer in hippocampus, striatum, hypothalamus and cortical areas was intermediate (5.0, 5.6, 4.2 and 5.6% ID/g, respectively) and low in the cerebellum (2.8% ID/g). The distribution of [F-18]FPH in the mouse brain matched that of other in vivo nAChR probes such as H-3-labeled epibatidine or norchloroepibatidine, [H-3](-)-nicotine and [H-3]cytisine and that of nAChR densities determined in postmortem autoradiographic studies in rodents. Preinjection of blocking doses of unlabeled epibatidine, (-)-nicotine, lobeline and cytisine significantly inhibited [F-18]FPH binding in thalamus and superior colliculus, but not in cerebellum, whereas drugs that interact with binding sites other than acetylcholine recognition sites of nAChR (e.g., mecamylamine, scopolamine, N-methylspiperone and ketanserin) had no effect on [F-18]FPH accumulation in any of the brain regions examined. Conclusion: Fluorine-18-FPH labels nAChR in vivo in the mouse brain. Because of its high uptake into the brain and high ratios of specific-to-nonspecific binding, this radioligand appears to be ideally suited for PET imaging of nAChR in the mammalian brain. C1 JOHNS HOPKINS UNIV,SCH MED,DIV NUCL MED,DEPT RADIOL,BALTIMORE,MD 21205. NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD. FU NCI NIH HHS [CA 32845]; NIDA NIH HHS [DA 06309] NR 39 TC 59 Z9 60 U1 0 U2 1 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 AUG PY 1997 VL 38 IS 8 BP 1260 EP 1265 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XP424 UT WOS:A1997XP42400025 PM 9255161 ER PT J AU Phillips, RL London, ED AF Phillips, RL London, ED TI Simplified calculation of MRglc using PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; METABOLIC-RATE; FLUORODEOXYGLUCOSE; BRAIN RP Phillips, RL (reprint author), NIDA,NIH,BALTIMORE,MD, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1997 VL 38 IS 8 BP 1334 EP 1334 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XP424 UT WOS:A1997XP42400046 PM 9255178 ER PT J AU De Luca, LM Kosa, K Andreola, F AF De Luca, LM Kosa, K Andreola, F TI The role of vitamin A in differentiation and skin carcinogenesis SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review DE retinoic acid; estrogen; nuclear receptors; differentiation; carcinogenesis; epithelium ID ACID RESPONSE ELEMENT; ACUTE PROMYELOCYTIC LEUKEMIA; DIETARY RETINOIC ACID; FEMALE SENCAR MICE; THYROID-HORMONE; NUCLEAR RECEPTORS; CARCINOMA FORMATION; X-RECEPTOR; MALIGNANT CONVERSION; TRANSCRIPTION FACTOR AB The field of vitamin A research has witnessed a remarkable surge in interest since the late 1980's, when the retinoid receptors were discovered and their genes cloned. Heterodimeric interactions between the retinoid X receptors (RXRs alpha, beta, and gamma), which bind 9-cis-retinoic acid, and other hormone receptors, including the retinoic acid receptors (RARs alpha, beta, and gamma), the thyroid hormone receptor (TR), the vitamin D receptor (VDR), the peroxisomal proliferator activated receptor (PPAR), and others make hormone action dependent on retinoid homeostasis. Retinoid response elements (RAREs) are present in the promoter and/or enhancer regions of several genes, including some of the homeobox genes, which control development and differentiation The interaction between hormones and retinoids is added additional orders of complexity by the diversity of the RAREs including the spacer length, their 5' or 3' position, and their coexistence in composite sequences with other hormone response elements (e.g., an estrogen response element in the lactalbumin gene promoter, see Table 2). Control of normal epithelial differentiation is a fundamental function of retinoids. The histogenesis of squamous metaplasia caused by vitamin A deficiency is a stepwise process, which permits the gradual transition of phenotypes from simple-columnar, typical of the endocervical epithelium, to pseudostratified, to stratified-squamous and, eventually to keratinizing. Conversely, the maintenance of the squamous keratinizing differentiation in the ectocervix and vagina requires estrogen. In the absence of this hormone, the squamous stratified ectocervical epithelium retrogrades to a simpler, two or three cell layer morphology, with the topmost layer expressing keratin K8, typical of the endocervical epithelium and mucous cells. Retinoid and estrogen receptor transcript expression is governed by dietary retinoid status and by estrogen availability with squamous cells mostly expressing RAR gamma and estrogen receptor transcripts, and columnar cells mostly expressing RAR beta. RXR transcripts appear mostly expressed in proliferating cells. The relevance of the retinoid receptors to carcinogenesis is highlighted in the work on acute promyelocytic leukemia. This work has demonstrated that the fusion gene PML-RAR alpha, resulting from the t(15;17) chromosomal translocation, is etiologically connected with the disease and with complete remission after oral retinoid administration. Developments in retinoid metabolism, including the clotting of the cytochrome P450RAI and the connection between RA metabolism and cell growth inhibition, have recently taken place. Recent work has also shown that pharmacological dietary retinoic acid specifically inhibits malignant conversion in the mouse two-stage carcinogenesis system. Because RA upregulates retinoid receptor expression, it seems that retinoid receptors function as tumor suppressors. This field should serve as a paradigm for things to come for other essential nutrients, and spells out the notion that nutritional sciences are indeed fundamentally important, because they can contribute significantly to our understanding of different diseases and provide effective therapeutic approaches. (C) 1997 Elsevier Science Inc. 1997. RP De Luca, LM (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH, BLDG 37,ROOM 3A-17, 37 CONVENT DR, BETHESDA, MD 20892 USA. OI Kosa, Karolina/0000-0001-7867-2403 NR 99 TC 22 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD AUG PY 1997 VL 8 IS 8 BP 426 EP 437 DI 10.1016/S0955-2863(97)00063-6 PG 12 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA XR597 UT WOS:A1997XR59700001 ER PT J AU Kontny, HU Sleasman, JW Kingma, DW Jaffe, ES Avila, NA Pizzo, PA Mueller, BU AF Kontny, HU Sleasman, JW Kingma, DW Jaffe, ES Avila, NA Pizzo, PA Mueller, BU TI Multilocular thymic cysts in children with human immunodeficiency virus infection: Clinical and pathologic aspects SO JOURNAL OF PEDIATRICS LA English DT Article ID LYMPHOEPITHELIAL LESION; MYASTHENIA-GRAVIS; HYPERPLASIA; CELLS; LYMPHOMAS; PATIENT; TUMORS AB Background: Children with human immunodeficiency virus (HIV) infection have an increased susceptibility to severe and unusual infections, malignancies, and disorders characterized by abnormal lymphoproliferation (e.g., lymphoid interstitial pneumonitis). We report a novel disease entity associated with pediatric HN infection that is characterized by massive enlargement of the thymus as a result of lymphoid hyperplasia and multicystic changes. Methods: Eight patients with HIV infection and cystic enlargement of the thymus are subject of this report. The status of their HIV disease and its clinical and radiologic manifestations at the time of diagnosis of the mediastinal mass are described. Tissue specimens mere obtained from six patients and examined by microscopy and immunohistochemistry, The specimens were also evaluated for the evidence of HIV and Epstein-Barr virus by in situ hybridization. Results: Patients were between 2.1 and 12.1 years of age, with CD4(+) cell counts between 102 and 733 cells/mm(3). In all eight cases an anterior mediastinal mass was discovered incidentally on radiography of the chest, and computed tomography of the chest revealed a multicystic appearance. Histologic examination demonstrated distortion of the thymic architecture by focal cystic changes, lymphoid follicular hyperplasia, diffuse plasmacytosis, and multinucleated giant cells. In situ hybridization revealed HIV particles on the surface of follicular dendritic cells. Further, results of in situ hybridization for EBV were positive in lymphoid cells from biopsy samples of four patients. The patients were followed between 8 months and 4.8 years. In five patients the mass either decreased in size or resolved completely. Conclusions: We describe a series of children with HN infection and multilocular thymic cysts. We hypothesize that aberrant immunoregulation in these HIV-infected children leads to follicular hyperplasia and multicystic changes in the thymus, causing massive enlargement. EBV infection might also contribute to the pathogenesis of this process. Because none of our patients had symptoms from the mass, and there was no evidence of malignancy in the examined biopsy samples, it seems prudent to manage such children with careful follow-up examinations. C1 NCI, HEMATOPATHOL SECT, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. UNIV FLORIDA, COLL MED, DEPT PEDIAT, GAINESVILLE, FL USA. NIH, DEPT DIAGNOST RADIOL, WARREN G MAGNUSON CLIN CTR, BETHESDA, MD 20892 USA. RP Kontny, HU (reprint author), NCI, PEDIAT BRANCH,DIV CLIN SCI,NIH,BLDG 10, ROOM 13N240, 10 CTR DR MSC 1182, BETHESDA, MD 20892 USA. NR 30 TC 20 Z9 20 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1997 VL 131 IS 2 BP 264 EP 270 DI 10.1016/S0022-3476(97)70164-1 PG 7 WC Pediatrics SC Pediatrics GA XU680 UT WOS:A1997XU68000021 PM 9290614 ER PT J AU Gasior, M Carter, RB Goldberg, SR Witkin, JM AF Gasior, M Carter, RB Goldberg, SR Witkin, JM TI Anticonvulsant and behavioral effects of neuroactive steroids alone and in conjunction with diazepam SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CALCIUM-CHANNEL BLOCKERS; BENZODIAZEPINE RECEPTOR; GABA RECEPTOR; ANTIEPILEPTIC DRUGS; HORMONE METABOLITES; INDUCED CONVULSIONS; CHLORIDE IONOPHORE; INDUCED SEIZURES; ESTRUS CYCLE; COCAINE AB Epilepsy continues to be a significant clinical problem as current medications neither adequately control seizures nor are free of untoward side-effects. Modulation of the neuroactive steroid site on the gamma-aminobutyric acid (GABA)(A) receptor complex may be an important new direction for pharmaceutical interventions in epilepsy. In this study we evaluated the protective actions of four neuroactive steroids, 3 alpha-hydroxy-5 alpha-pregnan-20-one, the 3 beta-methylated analog, ganaxolone (3 alpha-hydroxy-3 beta-methyl-5 alpha-pregnan-20-one), 3 alpha-hydroxy-5 beta-pregnan-20-one and Co 2-1068 (3 beta-(4acetylphenyl)ethynyl-3 alpha,21-dihydroxy-5 beta-20-one-21-hemisuccinate), against several standard convulsive tests in male, Swiss-Webster mice. Consistent with their GABAergic actions, the neuroactive steroids as well as diazepam and phenobarbital dose-dependently protected against clonic convulsions induced by pentylenetetrazol; the N-methyl-D-aspartate receptor antagonist, dizocilipine, was ineffective. In contrast to diazepam and phenobarbital, however, all of the neuroactive steroids and dizoclipine produced full protection against cocaine-induced convulsions. Some of the neuroactive steroids, as well as dizocilpine, were efficacious against the seizures and lethality induced by N-methyl-D-aspartate. Pregnenolone, a steroid devoid of GABAergic activity, was not effective in any of the convulsant models. Although all of the compounds produced motor toxicity in high doses as measured by the inverted-screen test, the neuroactive steroids demonstrated an equivalent or improved separation between anticonvulsant potency and motoric impairment. Inactive doses of the neuroactive steroids markedly enhanced the anticonvulsant effects of diazepam against pentylenetetrazol without significantly increasing motor toxicity. This adjunct treatment resulted in protective indices ranging from 60 to 360 compared to 12 for diazepam alone. The distinct profile of anticonvulsant activity of the neuroactive steroids may be related to their combined actions on gamma-aminobutyric acid, N-methyl-D-aspartate receptors, or voltage-operated Ca++ channels. These results help to define the neuroactive steroids as a novel class of antiepileptic agents and suggest their potential in clinical practice. C1 NIDA,ADDICT RES CTR,DRUG DEV GRP,NIH,BALTIMORE,MD 21224. COCENSYS INC,DEPT PHARMACOL,IRVINE,CA. RP Gasior, M (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,NIH,5500 NATHAN SHOCK DR,BALTIMORE,MD 21224, USA. NR 70 TC 110 Z9 112 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 AUG PY 1997 VL 282 IS 2 BP 543 EP 553 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XQ766 UT WOS:A1997XQ76600005 PM 9262314 ER PT J AU Mukhin, A Kovaleva, ES London, ED AF Mukhin, A Kovaleva, ES London, ED TI Two affinity states of N-methyl-D-aspartate recognition sites: Modulation by cations SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NMDA RECEPTOR-CHANNEL; H-3 MK-801 BINDING; RAT-BRAIN; NANOMOLAR AFFINITY; DIVALENT-CATIONS; COMPLEX; POLYAMINES; GLUTAMATE; NEURONS; GLYCINE AB Previous studies have indicated that inorganic and organic cations can markedly affect parameters of the function of the N-methyl-D-aspartate receptor ionophore complex. As these effects may involve modulation of agonist binding, the purpose of our study was to investigate the stimulatory effect of mono- and divalent cations on binding properties of glutamate/N-methyl-D-aspartate recognition sites on the N-methyl-D-aspartate receptor complex, using [H-3]CGP 39653 as the specific ligand for these sites. In well-washed membranes from rat brain, [H-3]CGP 39653 binding sites were present al two affinity states when assayed at 10 mM HEPES.KOH buffer. About 75% of these sites were in a low-affinity state (K-d = 210 +/- 30 nM) although 25% were in a high-affinity state (K-d = 6.4 +/- 0.4 nM). Addition of mono-or divalent cations to the incubation medium stimulated [H-3]CGP 39653 binding, measured at a radioligand concentration of 4 nM. Maximal increases in binding were to similar to 230 and 400% of control, in the presence of mono- and divalent cations, respectively. Values of EC50 for stimulation were 5 to 7 mM for monovalent cations and 0.2 to 0.4 mM for divalent cations. At these concentrations, cations increased the B-max for the high-affinity population of [H-3]CGP 39653 sites and decreased the B-max for low-affinity ones. These findings suggest that, like spermidine, inorganic cations stimulate binding by converting [H-3]CGP 39653 binding sites from the low-to high-affinity state. C1 NIDA,BRAIN IMAGING CTR,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. NR 37 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1997 VL 282 IS 2 BP 945 EP 954 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XQ766 UT WOS:A1997XQ76600053 PM 9262362 ER PT J AU Greenberg, SS Jie, OY Zhao, XF Xie, JM Wang, JF Giles, TD AF Greenberg, SS Jie, OY Zhao, XF Xie, JM Wang, JF Giles, TD TI Interaction of ethanol with inducible nitric oxide synthase messenger RNA and protein: Direct effects on autacoids and endotoxin in vivo SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-Heart-Association CY NOV 09-18, 1996 CL NEW ORLEANS, LA SP Amer Heart Assoc, Natl Inst Alcohol Abuse & Alcoholism ID VASCULAR SMOOTH-MUSCLE; IN-VIVO; ALVEOLAR MACROPHAGES; CYCLIC-AMP; MURINE MACROPHAGES; INDUCED EXPRESSION; TNF-ALPHA; CELLS; INDUCTION; LIPOPOLYSACCHARIDE AB Inducible nitric oxide synthase (iNOS) mRNA is up-regulated in vivo by dibutyryl-cAMP (db-cAMP), the purine-2y receptor agonist 2-methylthio-ATP and Escherichia coli endotoxin lipopolysaccharide (LPS). Ethanol and diethyldithiocarbamate inhibit LPS-stimulated iNOS mRNA. Their effects on db-cAMP- and 2-methylthio-ATP-stimulated iNOS mRNA remain undefined. We examined the effect of ethanol (4.5 g/kg intraperitoneal) and intratracheal diethyldithiocarbamate (5 mg/kg) on intratracheal LPS (0.6 mg/kg), db-cAMP (0.1 and 1 mg/kg) or 2-methylthio-ATP (5 mg/kg)-stimulated rat alveolar macrophage (AM) iNOS mRNA and protein, reactive nitrogen intermediates nitrite and nitrate anion (RNI) and nuclear transcription factor-kappa B (NF-kappa B) in vivo. LPS and the autacoids increased iNOS mRNA and protein in rat AM and RNI in bronchoalveolar lavage fluid and in ex vivo incubates of AM compared with these parameters in control rats (n = 6-21/group). Only LPS up-regulated TNF-alpha mRNA and release of TNF-alpha in bronchoalveolar lavage fluid and AM. Ethanol inhibited LPS stimulation of the iNOS cascade at the level of transcription but inhibited only autacoid-stimulated iNOS protein and RNI. Diethyldithiocarbamate selectively inhibited the LPS-stimulated iNOS cascade at the level of transcription. Coadministration of ethanol and diethyldithiocarbamate inhibited LPS-stimulated iNOS mRNA, protein and RNI more than either inhibitor alone but did not differ from ethanol alone on autacoid-stimulated iNOS protein or RNI. LPS increased and db-cAMP did not affect NF-kappa B in AM. Ethanol inhibited LPS-stimulated NF-kappa B. Thus, two distinct pathways exist for induction of iNOS mRNA in rat AM in vivo: an NF-kappa B pathway for LPS and cytokines inhibitable by ethanol and diethyldithiocarbamate and an NF-kappa B-independent pathway, refractory to inhibition by ethanol and diethyldithiocarbamate for db-cAMP and 2-mes-ATP. Finally, ethanol inhibits iNOS at the level of transcription and at the level of the enzyme. C1 LOUISIANA STATE UNIV, MED CTR, DEPT PHYSIOL, CARDIOVASC CTR EXCELLENCE, NEW ORLEANS, LA 70112 USA. LOUISIANA STATE UNIV, MED CTR, DEPT PHARMACOL, CARDIOVASC CTR EXCELLENCE, NEW ORLEANS, LA 70112 USA. RP Greenberg, SS (reprint author), LOUISIANA STATE UNIV, MED CTR,NIAAA,ALCOHOL RES CTR,DEPT MED, SECT CARDIOVASC RES, 1542 TULANE AVE, NEW ORLEANS, LA 70112 USA. FU NIAAA NIH HHS [NIAAA 1P50-AA09803, NIAAA 09816] NR 54 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1997 VL 282 IS 2 BP 1044 EP 1054 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XQ766 UT WOS:A1997XQ76600065 PM 9262374 ER PT J AU Cribb, AE Pohl, LR Spielberg, SP Leeder, JS AF Cribb, AE Pohl, LR Spielberg, SP Leeder, JS TI Patients with delayed-onset sulfonamide hypersensitivity reactions have antibodies recognizing endoplasmic reticulum luminal proteins SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HALOTHANE HEPATITIS PATIENTS; IDIOSYNCRATIC TOXICITY; DRUG HYPERSENSITIVITY; SERUM ANTIBODIES; STRESS PROTEINS; METABOLIC BASIS; LIVER; SULFAMETHOXAZOLE; HYDROXYLAMINE; AUTOANTIBODIES AB Sulfonamide antimicrobials cause a delayed-onset, hypersensitivity-type syndrome characterized by fever, skin rash and multiorgan toxicity occurring 7 to 14 days after initiation of therapy. The pathogenesis is believed to be immune-mediated. We investigated whether patients with delayed-onset sulfonamide hypersensitivity reactions had antibodies recognizing hapten-microsomal protein conjugates and/or native microsomal proteins. By immunoblotting using rat liver as a source of microsomal protein, 17 of 21 patients had antibodies recognizing one or more of three native endoplasmic reticulum proteins of 55 kDa (14 of 21 patients), 80 kDa (4 of 21 patients) or 96 kDa (3 of 21 patients) in size on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No control subjects (n = 11) and only 1 of 18 patients with adverse events not consistent with sulfonamide hypersensitivity reactions had antibodies against these microsomal proteins under the conditions used. Only 1 patient had antibodies that recognized the sulfonamide hapten, sulfamethoxazole. The 55-kDa protein was identified as protein disulfide isomerase. The 80-kDa protein was identified as grp78. The 96-kDa protein was not identified. Delayed-onset sulfonamide hypersensitivity reactions are therefore primarily associated with antibodies recognizing specific protein epitopes and not anti-drug antibodies. C1 MERCK RES LABS,W POINT,PA. NHLBI,LAB MOL IMMUNOL,MOL & CELLULAR TOXICOL SECT,NIH,BETHESDA,MD 20892. HOSP SICK CHILDREN,DIV CLIN PHARMACOL & TOXICOL,TORONTO,ON M5G 1X8,CANADA. NR 24 TC 41 Z9 41 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1997 VL 282 IS 2 BP 1064 EP 1071 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XQ766 UT WOS:A1997XQ76600067 PM 9262376 ER PT J AU Villalobos, AR Parmelee, JT Pritchard, JB AF Villalobos, AR Parmelee, JT Pritchard, JB TI Functional characterization of choroid plexus epithelial cells in primary culture SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ORGANIC CATION-TRANSPORT; IMMUNOCYTOCHEMICAL LOCALIZATION; GLUCOSE TRANSPORTER; CEREBROSPINAL-FLUID; MEMBRANE-VESICLES; PROXIMAL TUBULE; AMINO-ACIDS; RABBIT; CIMETIDINE; BRAIN AB The objective of this study was to develop and evaluate a primary culture system for choroid plexus epithelial cells as an in vitro model for studying organic cation transport. Cells were dispersed from choroid plexus of neonatal rats by enzymatic digestion and grew as differentiated monolayers when plated on solid or permeable support. Electron microscopy showed that cultured cells were morphologically similar to intact choroid plexus epithelium, having apical tight junctions between cells, numerous mitochondria, basal nuclei and apical microvilli and cilia, As previously demonstrated for intact choroid plexus, immunocytochemistry showed that Na+,K+-ATPase was localized to the apical membrane, and GLUT-1, the facilitative glucose transporter, was localized to the basolateral membrane of cultured cells. Apical transport of L-proline by cultured cells was mediated by a sodium-dependent, electrogenic process, as in whole tissue. C-14-Tetraethylammonium (TEA), a prototypic organic cation, was accumulated by isolated choroid plexus in a time-dependent manner; uptake was inhibited by tetrapentylammonium (TePA). In cultured cells, apical TEA transport was mediated by a saturable process coupled to cellular metabolism. Unlabeled TEA and other organic cations (TePA, N-1-methylnicotinamide and mepiperphenidol) inhibited TEA transport; the organic anion, p-aminohippurate, had no effect. Finally, TePA-sensitive transport of C-14-TEA was stimulated after preloading the cells with unlabeled TEA. Based on the morphological, biochemical and functional properties of these cultured cells, we conclude that this primary culture system should be an excellent in vitro model for experimental characterization of choroid plexus function. C1 NIEHS,LAB PHARMACOL & CHEM,NIH,RES TRIANGLE PK,NC 27709. BROWN UNIV,RHODE ISL HOSP,DEPT CLIN NEUROSCI,PROVIDENCE,RI 02903. NR 41 TC 40 Z9 42 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1997 VL 282 IS 2 BP 1109 EP 1116 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XQ766 UT WOS:A1997XQ76600072 PM 9262381 ER PT J AU Bahring, R Bowie, D Benveniste, M Mayer, ML AF Bahring, R Bowie, D Benveniste, M Mayer, ML TI Permeation and block of rat GluR6 glutamate receptor channels by internal and external polyamines SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID RECTIFIER K+ CHANNELS; INWARD-RECTIFIER; INTRACELLULAR SPERMINE; POTASSIUM CHANNEL; STRUCTURAL DETERMINANTS; HIPPOCAMPAL-NEURONS; RECTIFICATION; SODIUM; AMPA; MG2+ AB 1. Polyamine block of rat GauR6(Q) glutamate receptor channels was studied in outside-out patches from transiently transfected HEK 293 cells. With symmetrical 150 mM Na+ and 30 mu M internal spermine there was biphasic voltage dependence with 95% block at +40 mV but only 20% block at +140 mV. Dose-inhibition analysis for external spermine also revealed biphasic block; the K-d at +40 mV (54 mu M) was lower than at +80 (167 mu M) and -80 mV (78 mu M). 2. For internal polyamines relief from block was most pronounced for spermine, weaker for N-(4-hydroxyphenylpropanoyl)-spermine (PPS), and virtually absent for philanthotoxin 343 (PhTX 343), suggesting that permeation of polyamines varies with cross-sectional width(spermine, 0.44 nm; PPS, 0.70 nm; PhTX 343, 0.75 nm). 3. With putrescine, spermidine, or spermine as sole external cations, inward currents at -120 mV confirmed permeation of polyamines. For bi-ionic conditions with 90 mM polyamine and 150 mM Na-i(+), reversal potentials were -12.4 mV for putrescine (permeability ratio relative to Na+, P-Put/P-Na = 0.42) and -32.7 mV for spermidine (P-Spd/P-Na = 0.07). Currents carried by spermine were too small to analyse accurately in the majority of patches. 4. Increasing [Na+](i) from 44 to 330 mM had no effect on the potential for 50% block (V-1/2) by 30 mu M internal spermine; however, relief from block at positive membrane potentials increased with [Na+](i). In contrast, raising [Na+](o) from 44 to 330 mM resulted in a depolarizing shift in V-1/2, indicating a strong interaction between internal polyamines and external permeant ions. 5. The Woodhull infinite barrier model of ion channel block adequately described the action of spermine at membrane potentials insufficient to produce relief from block. For 30 mu M internal spermine such analysis gave K-d(0) = 2.5 mu M, z theta = 1.97; block by 30 mu M external spermine was weaker and less voltage dependent (K-d(0) = 37.8 mu M and z delta = 0.55); delta and theta are electrical distances measured from the outside and inside, respectively. 6. Fits of the Woodhull equation for a permeable blocker adequately described both onset and relief from block by spermine over a wide range of membrane potentials. However, the rate constants and z delta values estimated for block by internal spermine predicted much stronger external block than was measured experimentally, and vice versa. 7. An Eyring rate theory model with two energy wells and three barriers explained qualitatively many characteristic features of the action of polyamines on GluRs, including biphasic I-V relationships, weaker block by external than internal spermine and low permeability. C1 NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NIH,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT PHYSIOL & PHARMACOL,IL-69978 TEL AVIV,ISRAEL. RI Bahring, Robert/F-7146-2010; Mayer, Mark/H-5500-2013 NR 46 TC 83 Z9 85 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 1 PY 1997 VL 502 IS 3 BP 575 EP 589 DI 10.1111/j.1469-7793.1997.575bj.x PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA XR775 UT WOS:A1997XR77500011 PM 9279810 ER PT J AU Chen, JM Monaco, R Manolatos, S BrandtRauf, PW Friedman, FK Pincus, MR AF Chen, JM Monaco, R Manolatos, S BrandtRauf, PW Friedman, FK Pincus, MR TI Molecular dynamics on complexes of ras-p21 and its inhibitor protein, rap-1A, bound to the ras binding domain of the raf-p74 protein: Identification of effector domains in the raf protein SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE rap-1A and ras-p21 complexes with raf; ras-binding domain of raf; molecular dynamics; average structures; effector domains; signal transduction ID ENCODED P21 PROTEIN; CRYSTALLOGRAPHIC STRUCTURES; AMINO-ACIDS; GTP; CONFORMATIONS; RESOLUTION; P21(RAS); KINASE; GLY-12; GAP AB We have computed the average structures for the ras-p21 protein and its strongly homologous inhibitor protein, rap-1A, bound to the ras-binding domain (RED) of the raf protein, using molecular dynamics, Our purpose is to determine the differences in structure between these complexes that would result in no mitogenic activity of rap-1A-RBD but full activity of p21-RBD. We find that despite the similarities of the starting structures for both complexes, the average structures differ considerably, indicating that these two proteins do not interact in the same way with this vital target protein. p21 does not undergo major changes in conformation when bound to the RBD, while rap-1A undergoes significant changes in structure on binding to the RED, especially in the critical region around residue 61. The p21 and rap-1A make substantially different contacts with the RBD. For example, the loop region from residues 55-71 of rap-1a makes extensive hydrogen-bond contacts with the RBD, while the same residues of p21 do not. Comparison of the structures of the RBD in both complexes reveals that it undergoes considerable changes in structure when its structure bound to p21 is compared with that bound to rap-1A. These changes in structure are due to displacements of regular structure (e.g., alpha-helices and beta-sheets) rather than to changes in the specific conformations of the segments themselves. Three regions of the RBD have been found to differ significantly from one another in the two complexes: the binding interface between the two proteins at residues 60 and 70, the region around residues 105-106, and 118-120, These regions may constitute effector domains of the RBD whose conformations determine whether or not mitogenic signal transduction will occur. C1 VET AFFAIRS MED CTR,DEPT PATHOL & LAB MED,BROOKLYN,NY 11209. SUNY HLTH SCI CTR,DEPT PATHOL,BROOKLYN,NY 11203. DUPONT CO INC,STINE HASKELL RES CTR,DEPT AGR PROD,NEWARK,DE 19714. NYU,DEPT CHEM,NEW YORK,NY 10003. VET AFFAIRS MED CTR,DEPT RADIAT ONCOL,BROOKLYN,NY 11209. COLUMBIA UNIV COLL PHYS & SURG,DIV ENVIRONM SCI,NEW YORK,NY 10032. NIH,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 42500] NR 28 TC 9 Z9 11 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 AUG PY 1997 VL 16 IS 6 BP 619 EP 629 DI 10.1023/A:1026322924424 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP662 UT WOS:A1997XP66200005 PM 9263124 ER PT J AU Chung, D Amar, S Glozman, A Chen, JM Friedman, FK Robinson, R Monaco, R BrandtRauf, P Yamaizumi, Z Pincus, MR AF Chung, D Amar, S Glozman, A Chen, JM Friedman, FK Robinson, R Monaco, R BrandtRauf, P Yamaizumi, Z Pincus, MR TI Inhibition of oncogenic and activated wild-type ras-p21 protein-induced oocyte maturation by peptides from the ras-binding domain of the raf-p74 protein, identified from molecular dynamics calculations SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE ras-binding domain of raf; raf effector domain peptides; peptide inhibition of oocyte maturation; molecular dynamics ID XENOPUS OOCYTES; INSULIN; EXPRESSION; MUTANTS; GENE AB In the preceding paper we found from molecular dynamics calculations that the structure of the ras-binding domain (RED) of raf changes predominantly in three regions depending upon whether it binds to ras-p21 protein or to its inhibitor protein, rap-1A, These three regions of the RED involve residues from the protein-protein interaction interface, e.g., between residues 60 and 72, residues 97-110, and 111-121. Since the rap-1A-RBD complex is inactive, these three regions are implicated in ras-p21-induced activation of raf. We have therefore co-microinjected peptides corresponding to these three regions, 62-76, 97-110, and 111-121, into oocytes with oncogenic p21 and microinjected them into oocytes incubated in in insulin, which activates normal p21. All three peptides, but not a control peptide, strongly inhibit both oncogenic p21- and insulin-induced oocyte maturation, These findings corroborate our conclusions from the theoretical results that these three regions constitute raf effector domains. Since the 97-110 peptide is the strongest inhibitor of oncogenic p21, while the 111-121 peptide is the strongest inhibitor of insulin-induced oocyte maturation, the possibility exists that oncogenic and activated normal p21 proteins interact differently with the RBD of raf. C1 VET AFFAIRS MED CTR,DEPT PATHOL & LAB MED,BROOKLYN,NY 11209. SUNY HLTH SCI CTR,DEPT PATHOL,BROOKLYN,NY 11203. LONG ISL UNIV,DEPT CHEM,BROOKLYN,NY 11201. LONG ISL UNIV,DEPT BIOL,BROOKLYN,NY 11201. DUPONT CO INC,STINE HASKELL RES CTR,DEPT AGR PROD,NEWARK,DE 19714. NIH,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. NYU,DEPT BIOL,NEW YORK,NY 10003. COLUMBIA UNIV COLL PHYS & SURG,DIV ENVIRONM SCI,NEW YORK,NY 10032. NATL CANC INST,TOKYO,JAPAN. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 42500] NR 14 TC 17 Z9 17 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 AUG PY 1997 VL 16 IS 6 BP 631 EP 635 DI 10.1023/A:1026374908495 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP662 UT WOS:A1997XP66200006 PM 9263125 ER PT J AU Livneh, A Drenth, JPH Klasen, IS Langevitz, P George, J Shelton, DA Gumucio, DL Pras, E Kastner, DL Pras, M vanderMeer, JWM AF Livneh, A Drenth, JPH Klasen, IS Langevitz, P George, J Shelton, DA Gumucio, DL Pras, E Kastner, DL Pras, M vanderMeer, JWM TI Familial Mediterranean fever and hyperimmunoglobulinemia D syndrome: Two diseases with distinct clinical, serologic, and genetic features SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE familial Mediterranean fever; hyperimmunoglobulinemia D syndrome; IgA; IgD; chromosome 16; MEFV ID TUMOR-NECROSIS-FACTOR; PERIODIC-FEVER; COLCHICINE AB Objective. To determine whether the 2 periodic febrile syndromes familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS) are distinct diseases. Methods. Clinical manifestations of the diseases were analyzed by physicians experienced with FMF and HIDS. Serum immunoglobulin (Ig) levels were studied in 70 patients with FMF using nephelometry or ELISA and compared with Ig levels in 50 patients with HIDS. Genetic linkage of HIDS with the chromosome 16 polymorphic locus RT70, currently used for refined localization of the FMF susceptibility gene (MEFV), was studied in 9 HIDS families (18 patients) using polymerase chain reaction amplification and gel electrophoresis. Results. The main clinical features distinguishing FMF from HIDS were lymphadenopathy, skin eruption, and symmetrical oligoarthritis in HIDS, and monoarthritis, peritonitis, and pleuritis in FMF. Increased IgG levels were found in 12 patients with FMF (17%), IgA in 16 (23%), IgM in 9 (13%), and IgD in 9 (13%), significantly lower than the prevalence reported for HIDS. We found no evidence for genetic linkage between HIDS and the chromosome 16 marker RT70. Conclusion. HIDS and FMF are different entities, clinically, immunologically, and genetically. C1 TEL AVIV UNIV,SACKLER FAC MED,IL-69978 TEL AVIV,ISRAEL. UNIV NIJMEGEN ST RADBOUD HOSP,DEPT MED,NL-6500 HB NIJMEGEN,NETHERLANDS. UNIV NIJMEGEN ST RADBOUD HOSP,LABS CLIN CHEM,NL-6500 HB NIJMEGEN,NETHERLANDS. UNIV MICHIGAN,DEPT ANAT & CELL BIOL,ANN ARBOR,MI 48109. NIAMSD,ARTHRIT & RHEUMAT BRANCH,BETHESDA,MD 20892. RP Livneh, A (reprint author), CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. RI Drenth, J.P.H./H-8025-2014; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 NR 27 TC 33 Z9 33 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 1997 VL 24 IS 8 BP 1558 EP 1563 PG 6 WC Rheumatology SC Rheumatology GA XN705 UT WOS:A1997XN70500019 PM 9263151 ER PT J AU Stager, SV Denman, DW Ludlow, CL AF Stager, SV Denman, DW Ludlow, CL TI Modifications in aerodynamic variables by persons who stutter under fluency-evoking conditions SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE fluency evoking conditions; stuttering; intraoral pressure; air flow ID AIR-PRESSURE; SPEECH; SPEAKERS; EVENTS; VOICE AB The purposes of this study were to (a) compare the effects of fluency-evoking conditions on aerodynamic variables in 10 persons who stutter with those previously reported For 12 individuals who do not stutter; (b) determine if any changes demonstrated in the amplitude and/or timing of aerodynamic variables were accounted for by changes in speech intensity; and (c) determine if any amplitude or timing changes in flow and intraoral pressure were related to improved fluency. The fluency-evoking conditions were choral reading (CR), metronome-pacing (MET), delayed auditory feedback (DAF), and noise (NOISE). From 8 words beginning with plosive consonants in CVC contexts read aloud in sentences, measures were made of 8 variables, including closure duration, amplitude and time to maximum airflow and intraoral pressure for initial plosives, and the duration and intensity of the following vowel. Speech rate was also computed, Only Fluently produced target words From persons who stutter were analyzed. All persons who stutter showed improved fluency under all conditions. Both groups demonstrated significant (p less than or equal to 0.006) condition effects for peak flow, vowel intensity and pressure rise time. Thus, fluency-evoking conditions affected these variables regardless of speaker type. Both groups changed peak pressure in similar directions From baseline depending on condition, but not significantly for each group in the same conditions. Persons who stutter significantly increased speech rate for CR, DAF, and NOISE; and persons who do not stutter significantly decreased rate under DAF. The reported changes in peak pressure and peak flow could not be accounted for by changes in vowel intensity Larger improvements in fluency occurred under conditions when peak flow and peak pressure values were decreased From baseline. Thus, variables that were modified by both groups when speaking under conditions were also the variables related to changes in fluency for the persons who stutter. C1 NIDCD, VOICE & SPEECH SECT, NIH, BETHESDA, MD USA. UNIV MARYLAND, STAT LAB, COLLEGE PK, MD 20742 USA. OI Stager, Sheila/0000-0002-4294-2114; Ludlow, Christy/0000-0002-2015-6171 NR 36 TC 22 Z9 22 U1 0 U2 1 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD AUG PY 1997 VL 40 IS 4 BP 832 EP 847 PG 16 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA XQ964 UT WOS:A1997XQ96400010 PM 9263947 ER PT J AU Jensen, PS Martin, D Cantwell, DP AF Jensen, PS Martin, D Cantwell, DP TI Comorbidity in ADHD: Implications for research, practice, and DSM-V SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; comorbidity; etiology; classification ID ATTENTION-DEFICIT HYPERACTIVITY; ONTARIO CHILD HEALTH; CONDUCT DISORDER; RISK-FACTORS; LEARNING-DISABILITIES; JUVENILE-DELINQUENCY; GENERAL-POPULATION; TOURETTES-SYNDROME; PSYCHOPATHOLOGY; PREVALENCE AB Objective: Since the introduction of DSM-III/III-R, clinicians and investigators have shown increasing interest in the study of conditions comorbid with attention-deficit hyperactivity disorder (ADHD). Better understanding ADHD comorbidity patterns is needed to guide treatment, research, and future classification approaches. Method: The ADHD literature from the past 15 years was reviewed to (1) explore the most prevalent patterns of ADHD comorbidity; (2) examine the correlates and longitudinal predictors of comorbidity; and (3) determine the extent to which comorbid patterns convey unique information concerning ADHD etiology, treatment, and outcomes. To identify potential new syndromes, the authors examined comorbid patterns based on eight validational criteria. Results: The largest available body of literature concerned the comorbidity with ADHD and conduct disorder/aggression, with a substantially smaller amount of data concerning other comorbid conditions. In many areas the literature was sparse, and pertinent questions concerning comorbidity patterns remain unexplored. Nonetheless, available data warrant the delineation of two new subclassifications of ADHD: (1) ADHD, aggressive subtype, and (2) ADHD, anxious subtype. Conclusions: Additional studies of the frequency of comorbidity and associated factors are greatly needed, to include studies of differential effects of treatment of children with various comorbid ADHD disorders, as well as of ADHD children who differ on etiological factors. C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,LOS ANGELES,CA 90024. RP Jensen, PS (reprint author), NIMH,CHILD ADOLESCENT DISORDERS RES BRANCH,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 69 TC 387 Z9 398 U1 5 U2 38 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 1997 VL 36 IS 8 BP 1065 EP 1079 DI 10.1097/00004583-199708000-00014 PG 15 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA XM571 UT WOS:A1997XM57100014 PM 9256586 ER PT J AU Pfutzner, W Przybilla, B AF Pfutzner, W Przybilla, B TI Malignant melanoma and levodopa: Is there a relationship? Two new cases and a review of the literature SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID NONSUNLIGHT RISK-FACTORS; PARKINSONS-DISEASE; L-DOPA; PLASMA-LEVELS; ALPHA-MSH; DIAGNOSIS; THERAPY; CANCER; CELLS; CHEMOTHERAPY AB The incidence of malignant melanoma (MM) is rising. Besides UV radiation, other factors may contribute to this. We describe two patients in whom MM developed during treatment with levodopa. Levodopa has been implicated as an agent that could enhance the development of MM. However, review of the literature does not provide evidence of a definite relationship between treatment with levodopa and the development of MM. Despite this, it is suggested that patients treated with levodopa, particularly those with a history of MM, be observed carefully for changes in or development of new pigmented lesions. C1 UNIV MUNICH,DERMATOL KLIN & POLIKLIN,D-8000 MUNICH,GERMANY. RP Pfutzner, W (reprint author), NCI,DERMATOL BRANCH,NIH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. NR 68 TC 28 Z9 28 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 1997 VL 37 IS 2 SU S BP 332 EP 336 DI 10.1016/S0190-9622(97)70020-3 PN 2 PG 5 WC Dermatology SC Dermatology GA XT366 UT WOS:A1997XT36600013 PM 9270541 ER PT J AU Slavkin, HC AF Slavkin, HC TI Benefits and risks of medications: Challenges for the 21st century SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 2 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 AUG PY 1997 VL 128 IS 8 BP 1157 EP 1160 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XQ050 UT WOS:A1997XQ05000028 PM 9260429 ER PT J AU Schron, EB WassertheilSmoller, S Pressel, S AF Schron, EB WassertheilSmoller, S Pressel, S TI Clinical trial participant satisfaction: Survey of SHEP enrollees SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article AB OBJECTIVE: The purpose of this study was to determine older persons' reasons for joining a clinical trial, and to provide data that could be useful in planning and carrying out clinical trials in older and minority populations. DESIGN: A survey. PARTICIPANTS: The sample included 4281 men and women 60 years of age or older who were randomized to the Systolic Hypertension in the Elderly Program (SHEP). MEASUREMENTS: A 10-item satisfaction/attitude questionnaire was designed to evaluate (1) what personal benefits people expect from participation in this trial, (2) motivation for joining, and (3) satisfaction with clinic staff and operations. Each question had a response category asking for a measure of agreement, satisfaction, or importance. RESULTS: The most important reasons for joining the clinical trial were to contribute to science (96%), improve the health of others (96%), and improve their own health (93%). Free medical care and social aspects were less important reasons to join. There were no differences by treatment assignment, but differences in reasons for joining SHEP by age, race, gender, and education were observed, CONCLUSION: Older adults were enthusiastic about clinical trial participation. Recruitment, participant management strategies, and allocation of resources should consider the needs of specific patient groups. C1 ALBERT EINSTEIN COLL MED,NEW YORK,NY. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX. RP Schron, EB (reprint author), NHLBI,CLIN TRIALS SCI RES GRP,DIV EPIDEMIOL & CLIN APPLICAT,NIH,ROCKLEDGE CTR 2,ROOM 8144,BETHESDA,MD 20892, USA. NR 7 TC 33 Z9 33 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1997 VL 45 IS 8 BP 934 EP 938 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA XP436 UT WOS:A1997XP43600006 PM 9256844 ER PT J AU Shimizu, YK Igarashi, H Kanematu, T Fujiwara, K Wong, DC Purcell, RH Yoshikura, H AF Shimizu, YK Igarashi, H Kanematu, T Fujiwara, K Wong, DC Purcell, RH Yoshikura, H TI Sequence analysis of the hepatitis C virus genome recovered from serum, liver, and peripheral blood mononuclear cells of infected chimpanzees SO JOURNAL OF VIROLOGY LA English DT Article ID REPLICATION AB Of 13 different strains of hepatitis C virus (HCV) in the inoculum used, only 1 persisted in human lymphocyte cell lines infected in vitro (N. Nakajima, M. Hijikata, H. Yoshikura, and Y. K. Shimizu, J. Virol. 70:3325-3329, 1996). To determine whether that particular strain (designated H1-2) has a tropism for lymphocytes in vivo, we sequenced hypervariable region 1 (HVR1) of the genome of HCV recovered from the sera, livers, and peripheral blood mononuclear cells (PBMC) of chimpanzees infected with plasma H77, the same inoculum used for the in vitro studies, In the PBMC collected from two chimpanzees during the early phase of infection, H1-2 was detected as the only or predominant HVR1 sequence, H1-2 was also detected in PBMC obtained during persistent infection from a chimpanzee that had been treated with immunosuppressants, From the livers of these chimpanzees, two to six different strains were recovered but H1-2 was not detected. Thus, H1-2 appeared to have an affinity for lymphocytes not only in vitro but also in vivo. In samples collected from a chimpanzee after 6 years of infection, however, such tissue compartmentalization of the HCV genome was not observed; a single strain became predominant in the serum, liver, and PBMC. An HCV strain capable of replicating in both the liver and PBMC probably emerged during in vivo replication and persisted. C1 UNIV TOKYO,FAC MED,DEPT BACTERIOL,BUNKYO KU,TOKYO 113,JAPAN. SAITAMA MED SCH,DEPT INTERNAL MED 3,MOROYAMA,SAITAMA 35004,JAPAN. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP Shimizu, YK (reprint author), UNIV TOKYO,FAC MED,DEPT HEPATITIS VIROL SKBB,BUNKYO KU,7-3-1 HONGO,TOKYO 113,JAPAN. NR 17 TC 92 Z9 95 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1997 VL 71 IS 8 BP 5769 EP 5773 PG 5 WC Virology SC Virology GA XK153 UT WOS:A1997XK15300008 PM 9223464 ER PT J AU Juhasz, K Whitehead, SS Bui, PT Biggs, JM Boulanger, CA Collins, PL Murphy, BR AF Juhasz, K Whitehead, SS Bui, PT Biggs, JM Boulanger, CA Collins, PL Murphy, BR TI The temperature-sensitive (ts) phenotype of a cold-passaged (cp) live attenuated respiratory syncytial virus vaccine candidate, designated cpts530, results from a single amino acid substitution in the L protein SO JOURNAL OF VIROLOGY LA English DT Article ID SERONEGATIVE CHIMPANZEES; CLONED CDNA; RSV; MUTANT; IMMUNOGENICITY; IMMUNIZATION; MUTATIONS; EFFICACY; GENE; DNA AB cpts530, a candidate live-virus vaccine, is an attenuated strain of human respiratory syneytial virus (RSV). It was derived by subjecting a cold-passaged (cp) strain of RSV to 3 single round of chemical mutagenesis. cpts530 is a temperature-sensitive (ts) mutant that is attenuated in mice and chimpanzees, and its ts phenotype exhibits a high level of stability during replication in both species, In the present study, the complete nucleotide sequence of cpts530 RSV was determined, The five mutations known to be present In the parent cpRSV were retained in its cpts530 derivative, and one additional nucleotide change was identified at nucleotide (nt) 10060, which resulted in a phenylalanine-to-leucine change at amino acid 521 in the large polymerase (L) protein, To determine if this single amino acid substitution was indeed responsible for the ts phenotype of cpts530, it was introduced alone or in combination with the cp mutations into the full-length cDNA clone of the wild-type A2 RSV. Analysis of infectious viruses recovered from mutant cDNAs indicated that this single mutation specified complete restriction of plaque formation of recombinant cp530 in HEp-2 cell monolayer cultures at 40 degrees C, and the level of temperature sensitivity was not influenced by the presence of the five cpRSV mutations, These findings identify the phenylalanine-to-leucine change at amino acid 521 in the L protein as the mutation that specifies the rs phenotype of cpts530, Furthermore, these findings illustrate the feasibility; of using the cDNA-based recovery system to analyze and construct defined attenuated vaccine viruses. RP Juhasz, K (reprint author), NIAID,LID,NIH,7 CTR DR,MSC-0720,BETHESDA,MD 20892, USA. NR 21 TC 47 Z9 48 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1997 VL 71 IS 8 BP 5814 EP 5819 PG 6 WC Virology SC Virology GA XK153 UT WOS:A1997XK15300014 PM 9223470 ER PT J AU Lee, S Peden, K Dimitrov, DS Broder, CC Manischewitz, J Denisova, G Gershoni, JM Golding, H AF Lee, S Peden, K Dimitrov, DS Broder, CC Manischewitz, J Denisova, G Gershoni, JM Golding, H TI Enhancement of human immunodeficiency virus type 1 envelope-mediated fusion by a CD4-gp120 complex-specific monoclonal antibody SO JOURNAL OF VIROLOGY LA English DT Article ID CONFORMATION-DEPENDENT EPITOPES; SOLUBLE CD4 BINDING; CELL-LINE; CD4-MEDIATED FUSION; GP120; GLYCOPROTEIN; NEUTRALIZATION; INFECTION; HIV-1; DOMAIN AB The entry of human immunodeficiency virus type 1 (HIV-1) into cells is initiated by binding of the viral glycoprotein gp120-gp41 to its cellular receptor CD4, The gp120-CD4 complex formed at the cell surface undergoes conformational changes that may allow its association with an additional membrane component(s) and the eventual formation of the fusion complex, These conformational rearrangements are accompanied by immunological changes manifested by altered reactivity with monoclonal antibodies specific for the individual components and presentation of new epitopes unique to the postbinding complex, In order to analyze the structure and function of the gp120-CD4 complex, monoclonal antibodies were generated from splenocytes of BALB/c mice immunized with soluble CD4 gp120 (IIIB) molecules (J. M. Gershoni, G. Denisova, D. Raviv, N. J. Smorodinsky, and D. Buyaner, FASEB J. 7:1185-1187 1993). One of those monoclonal antibodies, CG10, was found to be strictly complex specific, Here we demonstrate that this monoclonal antibody can significantly enhance the fusion of CD4(+) cells with effector cells expressing multiple HIV-1 envelopes, Both T-cell-line-tropic and macrophage-tropic envelope-mediated cell fusion were enhanced, albeit at different optimal doses, Furthermore, infection of HeLa CD4(+) (MAGI) cells by HIV-1 LAI, ELI1, and ELI2 strains was increased two- to fourfold in the presence of CG10 monoclonal antibodies, suggesting an effect on viral entry. These findings indicate the existence of a novel, conserved CD4-gp120 intermediate structure that plays an important role in HIV-1 cell fusion. C1 US FDA,LAB RETROVIRUS RES,DIV VIRAL PROD,CBER,BETHESDA,MD 20892. NCI,SECT MEMBRANE STRUCT & FUNCT,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT CELL RES & IMMUNOL,IL-69978 TEL AVIV,ISRAEL. NR 43 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1997 VL 71 IS 8 BP 6037 EP 6043 PG 7 WC Virology SC Virology GA XK153 UT WOS:A1997XK15300039 PM 9223495 ER PT J AU Masuda, M Hanson, CA Dugger, NV Robbins, DS Wilt, SG Ruscetti, SK Hoffman, PM AF Masuda, M Hanson, CA Dugger, NV Robbins, DS Wilt, SG Ruscetti, SK Hoffman, PM TI Capillary endothelial cell tropism of PVC-211 murine leukemia virus and its application for gene transduction SO JOURNAL OF VIROLOGY LA English DT Article ID KAPOSIS-SARCOMA; NEUROPATHOGENIC VARIANT; ECOTROPIC RETROVIRUS; MOLECULAR-CLONING; SURFACE-ANTIGENS; RAT; EXPRESSION; INFECTION; BRAIN; SEQUENCES AB PVC-211 murine leukemia virus (MuLV) causes neurodegenerative disease following inoculation of neonatal, but not adult, mice and rats. It was previously shown that tropism from capillary endothelial cells (CEC) was a determinant of the viral neuropathogenicity. In this study, we demonstrate that host age-dependent replication of PVC-211 MuLV in vivo occurs in CEC in the brain as well as in other organs, such as the liver, kidney, and heart. In contrast, primary explant cultures of CEC derived from brains and livers of adult and neonatal rats could be infected by PVC-211 MuLV, suggesting that the age-dependent susceptibility was abrogated in vitro. Although CEC were generally less susceptible to MuLV-mediated age transduction than fibroblasts, treatment of CEC with 2-deoxyglucose followed by inoculation of a PVC-211 MuLV-pseudotyped vector in the absence of heparin improved the transduction efficiency. These observations support the possibility that PVC-211 MuLv may be useful for establishing models of CEC gene transduction. C1 DEPT VET AFFAIRS MED CTR,RES SERV,BALTIMORE,MD 21201. NCI,MOL ONCOL LAB,FREDERICK,MD 21702. SAIC,LAB CELLULAR BIOCH,FREDERICK,MD 21702. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT NEUROL,BALTIMORE,MD 21201. NR 31 TC 11 Z9 11 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 AUG PY 1997 VL 71 IS 8 BP 6168 EP 6173 PG 6 WC Virology SC Virology GA XK153 UT WOS:A1997XK15300055 PM 9223511 ER PT J AU Roden, RBS Armstrong, A Haderer, P Christensen, ND Hubbert, NL Lowy, DR Schiller, JT Kirnbauer, R AF Roden, RBS Armstrong, A Haderer, P Christensen, ND Hubbert, NL Lowy, DR Schiller, JT Kirnbauer, R TI Characterization of a human papillomavirus type 16 variant-dependent neutralizing epitope SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; ANTIBODY-MEDIATED NEUTRALIZATION; MONOCLONAL-ANTIBODY; VACCINIA VIRUS; L1; L2; IMMUNIZATION; PERSPECTIVE; PROTEINS; CAPSIDS AB We have determined that three type-specific and conformationally dependent monoclonal antibodies, H16.E70, H16.U4, and H16.V5, neutralize pseudotype human papillomavirus type 16 (HPV16) virions in vitro. H16.U4 and K16.V5 neutralized pseudotype virions derived from the German HPV16 variant 114K and the Zairian variant Z-1194 with equal efficiency. In contrast, neutralization of Z-1194 pseudotype virions by H16.E70 was two orders of magnitude weaker than neutralization of 114K pseudotype virions. This difference correlated with enzyme-linked immunosorbent assay reactivity of H16.E70 to L1 virus-like particles of the two variants. A substitution at residue 282 of L1 was responsible for this differential reactivity, suggesting that this residue constitutes part of the H16.E70 epitope. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PATHOL,HERSHEY,PA 17033. UNIV VIENNA,SCH MED,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,A-1090 VIENNA,AUSTRIA. RP Roden, RBS (reprint author), NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892, USA. NR 39 TC 83 Z9 87 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 AUG PY 1997 VL 71 IS 8 BP 6247 EP 6252 PG 6 WC Virology SC Virology GA XK153 UT WOS:A1997XK15300071 PM 9223527 ER PT J AU Mahieux, R PeconSlattery, J Gessain, A AF Mahieux, R PeconSlattery, J Gessain, A TI Molecular characterization and phylogenetic analyses of a new, highly divergent simian T-cell lymphotropic virus type 1 (STLV-1marc1) in Macaca arctoides SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; HTLV-I VARIANT; LEUKEMIA-VIRUS; STLV-I; AFRICA; LYMPHOMA; ORIGIN; TRANSMISSION; STRAINS; PYGMIES AB A serological sun ey of a captive colony of Asian monkeys indicated that six Macaca arctoides had antibodies to human T-cell leukemia/lymphotropic viruses (HTLV). Over a 4-year interval, sera from these animals continued to exhibit a peculiar Western blot (WB) pattern resembling an HTLV-2 pattern (p24(gag) reactivity of equal or greater intensity than that of p19(gag) and a strong reactivity to recombinant gp21) but also exhibiting, in five of six: cases, a reactivity against MTA-1, an HTLV-1 gp46 peptide. PCR experiments on DNA extracted from peripheral blood mononuclear cells using HTLV-1- or HTLV-2-specific long terminal repeat, gag, pal, env, and tax primers yielded negative results, However, highly conserved primers successfully amplified three different gene segments of env, tax, and env-tax. The results of comparative sequence analysis demonstrated that STLV-1marc1 was not closely related to any known STLV-1 strain, was the most divergent strain of the HTLV-1-STLV-1 group, and lacked the ATG initiation codons corresponding to the p12 and p13 proteins of HTLV-1. Phylogenetic analyses incorporating representative strains of all known HTLV-STLV clades consistently depicted STLV-1marc1 within the HTLV-1-STLV-1 type 1 lineage, but it probably diverged early, since its position is clearly different from all known viral strains of this group and it had a bootstrap resampling value of 100%. Genetic distance estimates between STLV-1marc1 and all other type I viruses were of the same order of magnitude as those between STLV-2PanP and all other type 2 viruses, In light of the recent demonstration of interspecies transmission of some STLV-1 strains, our results suggest the existence in Asia of HTLV-1 strains related to this new divergent STLV-1marc1 strain, which may be derived from a common ancestor ear ly in the evolution of the type I viruses and could be therefore considered a prototype of a new HTLV-STLV clade. C1 INST PASTEUR,DEPT RETROVIRUS,UNITE EPIDEMIOL VIRUS ONCOGENES,F-75728 PARIS 15,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,LAB GENOM DIVERS,FREDERICK,MD. NR 33 TC 34 Z9 34 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1997 VL 71 IS 8 BP 6253 EP 6258 PG 6 WC Virology SC Virology GA XK153 UT WOS:A1997XK15300072 PM 9223528 ER PT J AU Cowan, LD Go, OT Howard, BV Devereux, RB Pettitt, DJ Fabsitz, RR Lee, ET Welty, TK AF Cowan, LD Go, OT Howard, BV Devereux, RB Pettitt, DJ Fabsitz, RR Lee, ET Welty, TK TI Parity, postmenopausal estrogen use, and cardiovascular disease risk factors in American Indian women: The Strong Heart Study SO JOURNAL OF WOMENS HEALTH LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; FOLLOW-UP; PLASMA-FIBRINOGEN; LIFE-STYLE; ASSOCIATION; POPULATION; MORTALITY; MENOPAUSE; THERAPY; HEALTH AB Studies have suggested that high parity is related to an increased risk of cardiovascular disease (CVD). Reasons for an increased risk are unclear but may include influences of child-bearing on levels of CVD risk factors. The present study examined the associations of parity and CVD risk factors in American Indian women, among whom large families are common. Estrogen use and CVD risk factors also were assessed. The study included 1982 ever-married, postmenopausal women aged 45 through 74 years who participated in the Strong Heart Study (SHS), a large study of American Indians in three geographic areas of the United States. Information was obtained during a physical examination and interview. Parity ranged from 0 to 18 (median 5). Current estrogen use varied from 5% in Arizona to 21% in Oklahoma. Multivariable analyses found a statistically significant, inverse association between parity and high-density lipoprotein (HDL) cholesterol, although the difference with increasing parity was small (-0.26 mg/dl per additional live birth). Estrogen users had significantly lower levels of low-density lipoprotein cholesterol (-6.4 mg/dl) and fibrinogen (-26.2 mg/dl) and a lower waist/hip ratio (-0.02), and higher values of HDL (5 mg/dl) and logarithm (In) triglyceride (0.13 mg/dl). Current users were slightly more likely to be hypertensive (prevalence odds ratio, 1.56). Relations between parity and CVD risk factors in American Indian women with high parity suggested only small differences with increasing parity. Associations with estrogen use are much stronger and are similar to those observed in other groups of women. C1 UNIV OKLAHOMA,CTR AMER INDIAN HLTH RES,OKLAHOMA CITY,OK. MEDLANT HLTH CARE GRP,MEDLANT RES INST,WASHINGTON,DC. CORNELL MED CTR,NEW YORK,NY. NIDDKD,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ. NHLBI,BETHESDA,MD 20892. ABERDEEN AREA INDIAN HLTH SERV,RAPID CITY,SD. RP Cowan, LD (reprint author), UNIV OKLAHOMA,HLTH SCI CTR,COLL PUBL HLTH,DEPT BIOSTAT & EPIDEMIOL,POB 26901,OKLAHOMA CITY,OK 73190, USA. FU NHLBI NIH HHS [U01-HL41654, U01-HL41652, U01-HL41642] NR 37 TC 26 Z9 27 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1059-7115 J9 J WOMENS HEALTH JI J. Womens Health PD AUG PY 1997 VL 6 IS 4 BP 441 EP 449 DI 10.1089/jwh.1997.6.441 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA XW097 UT WOS:A1997XW09700023 PM 9279832 ER PT J AU Newton, KM LaCroix, AZ Leveille, SG Rutter, C Keenan, NL Anderson, LA AF Newton, KM LaCroix, AZ Leveille, SG Rutter, C Keenan, NL Anderson, LA TI Women's beliefs and decisions about hormone replacement therapy SO JOURNAL OF WOMENS HEALTH LA English DT Article ID MIDDLE-AGED WOMEN; ESTROGEN REPLACEMENT; ATTITUDES; INFORMATION; MENOPAUSE; KNOWLEDGE; PERIMENOPAUSAL; DETERMINANTS; OSTEOPOROSIS; VIEWS AB To examine preventive health practices in older women, we conducted computer-assisted telephone interviews with 1082 women aged 50-80 who were enrollees of Group Health Cooperative of Puget Sound (June-November 1995; 80.3% response rate). We sought to describe the women's reasons for initiating, discontinuing, or not initiating hormone replacement therapy (HRT). HRT use was categorized as current (42.5%), past (20.9%), or never (36.6%) based on the interviews. The reasons most frequently cited by current users for initiating HRT were menopausal symptoms (47.3%), osteoporosis prevention (32.4%), and physician advice (30.3%). The most frequently cited reasons for quitting HRT were side effects (26.6%), physician's advice (22.9%), fear of cancer (15.4%), and not wanting menstrual periods or bleeding (15.2%). Of past users, 53.8% report-ed stopping HRT on their own, and 46.2% did so at their physician's advice. The reasons most commonly cited by never users for not initiating HRT were that hormones were not needed (49.9%) and that menopause is a natural event (17.9%). Among never users, 33.1% reported considering HRT, only 46.6% discussing it with their provider, and 5.0% being given an HRT prescription they did not fill. Many women made decisions about HRT independent of interactions with health care providers. Better understanding of the beliefs and decisions that influence women's choice to use or not use HRT is needed to develop more effective counseling strategies. C1 NIA,GAITHERSBURG,MD. CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,ATLANTA,GA. RP Newton, KM (reprint author), GRP HLTH COOPERAT PUGET SOUND,CTR HLTH STUDIES,1730 MINOR AVE,SUITE 1600,SEATTLE,WA 98101, USA. FU PHS HHS [U48/CCU009654-04] NR 25 TC 91 Z9 91 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1059-7115 J9 J WOMENS HEALTH JI J. Womens Health PD AUG PY 1997 VL 6 IS 4 BP 459 EP 465 DI 10.1089/jwh.1997.6.459 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA XW097 UT WOS:A1997XW09700025 PM 9279834 ER PT J AU Takayama, H LaRochelle, WJ Sabnis, SG Otsuka, T Merlino, G AF Takayama, H LaRochelle, WJ Sabnis, SG Otsuka, T Merlino, G TI Renal tubular hyperplasia, polycystic disease, and glomerulosclerosis in transgenic mice overexpressing hepatocyte growth factor scatter factor SO LABORATORY INVESTIGATION LA English DT Article ID C-MET RECEPTOR; EPITHELIAL-CELLS; FACTOR/SCATTER FACTOR; KIDNEY DEVELOPMENT; MOUSE; REGENERATION; MITOGEN; INJURY; RATS; MYC AB Hepatocyte growth factor/scatter factor (HGF/SF) has been implicated as a renotrophic agent, capable of stimulating renal regeneration after unilateral nephrectomy or acute kidney failure. However, evaluation of the therapeutic utility of HGF/SF requires thorough analysis of its effects in an appropriate in vivo model system. To this end, the renal structure and function in HGF/SF transgenic mice were examined. Mice overexpressing HGF/SF in the kidney and serum demonstrated prominent tubular cystic disease and progressive glomerulosclerosis, and were susceptible to premature death from renal failure. The tubular phenotype appeared to result from HGF/SF-Met autocrine stimulation of the tubular epithelium and consequent hyperplasia. Electron microscopic examination of glomeruli, which also showed enhanced cellular proliferation, revealed ultrastructural features consistent with focal segmental glomerulosclerosis: an increase in mesangial matrix, effacement of foot processes, and thickening of basement membrane. These changes were not present at birth but developed progressively with age, which is consistent with the notion that HGF/SF may not be essential for the early stages of nephrogenesis, but may play an important role in renal epithelial renewal and regeneration. Thus, HGF/SF transgenic mice could be a useful model for dissecting the molecular mechanisms leading to polycystic disease and focal segmental glomerulosclerosis. Moreover, our results suggest that caution should be used when considering HGF/SF as a future therapeutic agent. C1 NCI,MOL BIOL LAB,MOL GENET SECT,NIH,BETHESDA,MD 20892. NCI,MOL & CELLULAR BIOL LAB,NIH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT GENITOURINARY PATHOL,DIV NEPHROPATHOL,WASHINGTON,DC 20306. NR 42 TC 68 Z9 71 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 AUG PY 1997 VL 77 IS 2 BP 131 EP 138 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA XR748 UT WOS:A1997XR74800003 PM 9274855 ER PT J AU Delporte, C Redman, RS Baum, BJ AF Delporte, C Redman, RS Baum, BJ TI Relationship between the cellular distribution of the alpha(v)beta(3/5) integrins and adenoviral infection in salivary glands SO LABORATORY INVESTIGATION LA English DT Article ID MEDIATED GENE-TRANSFER; VECTOR; CDNA AB This study compared the localization of the alpha,beta(3/5) integrins in the different cell types of the rat submandibular gland with the susceptibility of these cells to infection by an intraductally administered replication-deficient recombinant type 5 adenovirus coding for rat aquaporin 5 (termed AdrAQP5). We used a panel of antibodies and immunohistochemical procedures to determine the luminal membrane distribution of the integrins. The alpha(v) beta(3/5) integrin subunits were present in luminal membranes of all ductal cell types and acini; however, the alpha(v) subunit was found to a lesser extent in the acini. After AdrAQP5 infection, the expression of AQP5 exhibited a similar, though not identical, cellular localization to that seen for alpha(v) beta(3/5) integrins. AdrAQP5 infected all cell types in these glands, except excretory ducts, after intraductal administration, directing the transient expression of AQP5. In addition, the localization of alpha(v) beta(3/5) integrins was examined in rabbit, monkey, and human submandibular and parotid glands. Although there were some interspecies differences, glands generally displayed the presence of these integrin subunits on luminal membranes of ductal cells and most acinar cells. These findings show that the presence of alpha(v) beta(3/5) integrins on the luminal membranes of rat salivary epithelial cells is associated with the susceptibility of these cells to act as targets for adenoviral-mediated gene transfer. However, the abundance of alpha(v) beta(3/5) integrin expression was not necessarily predictive of the extent of transgene expression in a particular cell type. Furthermore, because the salivary glands of rabbits, monkeys, and humans show a similar luminal membrane distribution of these integrins, it is likely that recombinant type 5 adenoviruses may be able to mediate in vivo gene transfer to salivary glands in these species. C1 NIDR,GENE THERAPY & THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. DEPT VET AFFAIRS MED CTR,ORAL PATHOL RES LAB,WASHINGTON,DC. RI Delporte, Christine/A-5733-2012 NR 32 TC 43 Z9 45 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD AUG PY 1997 VL 77 IS 2 BP 167 EP 173 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA XR748 UT WOS:A1997XR74800007 PM 9274859 ER PT J AU Thomas, GR Greenberg, J Wu, KT Moe, K Esclamado, R Bradford, C Carroll, W Eisbruch, A Urba, S Wolf, GT AF Thomas, GR Greenberg, J Wu, KT Moe, K Esclamado, R Bradford, C Carroll, W Eisbruch, A Urba, S Wolf, GT TI Planned early neck dissection before radiation for persistent neck nodes after induction chemotherapy SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 4th International Conference on Head and Neck Cancer CY JUL 27-AUG 02, 1996 CL TORONTO, CANADA ID ADVANCED RESECTABLE HEAD; LOCALLY ADVANCED HEAD; ORGAN PRESERVATION; ADJUVANT CHEMOTHERAPY; ONCOLOGY-GROUP; PHASE-I/II; CANCER; CARCINOMA; CISPLATIN; THERAPY AB Optimal management of advanced neck metastases as part of an organ preservation treatment approach for head and neck squamous carcinoma (HNSC) is unclear. Since 1989, our management paradigm for patients on organ preservation was modified to incorporate planned early neck dissection before radiation therapy for patients who did not achieve a complete response (CR) of neck nodes after induction chemotherapy (IC). The purpose of this study was to determine if planned early neck dissection is a safe and effective approach in the management of advanced nodal disease as part of organ preservation. Fifty-eight consecutive patients with advanced HNSC who were entered in organ preservation trials using induction chemotherapy and radiation with surgical salvage were studied. Median follow-up was 26 months. Of the 58 patients, 71% were stage IV. Patients were grouped by nodal response to chemotherapy and N class, and were analyzed with respect to patterns of recurrence, complications, and survival. Overall, the rate of CR of neck nodes was 48%. Fifty-one percent had less than a complete response of neck nodes after IC and required planned early neck dissection. There were no significant differences in patterns of recurrence, complications, interval time to start of radiation, recurrence, or survival rates between the CR and less than CR groups. These data suggest that planned early neck dissection for patients with less than CR in the neck after IC is not detrimental with respect to neck relapse or overall survival. We believe that planned early neck dissection can be safely incorporated into future organ preservation treatment protocols for patients with advanced head and neck carcinoma. C1 UNIV MICHIGAN,DEPT OTOLARYNGOL HEAD & NECK SURG,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT RADIAT ONCOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT MED,ANN ARBOR,MI 48109. NIDCD,HEAD & NECK TUMOR BIOL SECT,NIH,BETHESDA,MD. NIDCD,EPIDEMIOL STAT & DATA SYST BRANCH,NIH,BETHESDA,MD. NR 18 TC 12 Z9 13 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD AUG PY 1997 VL 107 IS 8 BP 1129 EP 1137 DI 10.1097/00005537-199708000-00023 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA XQ523 UT WOS:A1997XQ52300023 PM 9261021 ER PT J AU Clausen, PA Athanasiou, M Chen, Z Dunn, KJ Zhang, Q Lautenberger, JA Mavrothalassitis, G Blair, DG AF Clausen, PA Athanasiou, M Chen, Z Dunn, KJ Zhang, Q Lautenberger, JA Mavrothalassitis, G Blair, DG TI ETS-1 induces increased expression of erythroid markers in the pluripotent erythroleukemic cell lines K562 and HEL SO LEUKEMIA LA English DT Article DE ETS-1; erythroid differentiation; hematopoiesis; signal transduction; transcriptional activation ID MURINE LEUKEMIA-VIRUS; ONCOGENE FAMILY MEMBER; HUMAN MYELOID-LEUKEMIA; TRANSCRIPTION FACTORS; C-MYC; TERMINAL DIFFERENTIATION; TRANSFORMING GENE; T-CELLS; PROTOONCOGENE; BINDING AB Members of the ETS gene family are known to be expressed in hematopoietic tissues and cell lines, and there is increasing evidence that ETS proteins may play a role in normal hematopoietic cell development. We demonstrate that ETS-1 can contribute to the development of an erythroid phenotype in vitro. The pluripotent erythroleukemic K562 and HEL cell lines express messages for a number of ETS genes, but only c-ETS-1 levels are elevated in response to treatment with hemin or cytosine arabinofuranoside (Ara-C), agents which induce erythroid differentiation. Furthermore, ETS-1 antisense oligonucleotides inhibit hemoglobinization of cells treated with Ara-C or hemin, and K562 and HEL cells infected with retrovirus expressing the c-ETS-1 gene exhibit a significant increase in erythroid character (as indicated by benzidine staining for hemoglobin (Hb) and surface marker analysis), a dramatic increase in responsiveness to hemin or Ara-C, and a decreased rate of proliferation (20-40% of control rates). In contrast, infection with virus expressing ETS-2 or vector sequences only causes no detectable changes in the proliferation or erythroid character of either the HEL or K562 cell lines. These data indicate a role for ETS-1 in erythroid differentiation. C1 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD. RP Clausen, PA (reprint author), NCI,BASIC RES LAB,DIV BASIC SCI,POB B,FREDERICK,MD 21702, USA. NR 82 TC 21 Z9 24 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 1997 VL 11 IS 8 BP 1224 EP 1233 DI 10.1038/sj.leu.2400735 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA XR625 UT WOS:A1997XR62500008 PM 9264374 ER PT J AU Shimizu, T Pommier, Y AF Shimizu, T Pommier, Y TI Camptothecin-induced apoptosis in p53-null human leukemia HL60 cells and their isolated nuclei: effects of the protease inhibitors Z-VAD-fmk and dichloroisocoumarin suggest an involvement of both caspases and serine proteases SO LEUKEMIA LA English DT Article DE camptothecin; topoisomerase I; apoptosis; caspase; serine protease; HL60 ID TOPOISOMERASE-II INHIBITORS; HL-60 CELLS; INTERLEUKIN-1-BETA-CONVERTING ENZYME; DNA FRAGMENTATION; FAS/APO-1-MEDIATED APOPTOSIS; POLY(ADP-RIBOSE) POLYMERASE; DIFFERENTIAL INDUCTION; ICE/CED-3 PROTEASE; MICE DEFICIENT; T-LYMPHOCYTES AB The human leukemia cell line, HL60 is very sensitive to various apoptotic stimuli and p53-null. The death-related cysteine proteases of the caspases family play a central role in the execution phase of apoptosis, and we recently reported the importance of serine protease activation in camptothecin-induced apoptotic endonuclease activation in HL60 cells. In the present study, we investigated the role of caspases (ICE/CED-3-related cysteine proteases) and serine proteases in cell death induced by the topoisomerase I inhibitor, camptothecin, in HL60 cells and in a cell-free system. We found that CPP32 is activated during camptothecin-induced apoptosis, and that N- benzyloxycarbony-Val-Ala-Asp (O-methyl) -fluoromethyketone (Z-VAD-fmk), a cell permeable caspase inhibitor blocks all features of apoptosis: morphological changes, cleavage of caspase 3 (CPP32/Yama/Apopain) and poly(ADP-ribose) polymerase, lamin B degradation and DNA fragmentation, However, Z-VAD-fmk and two other ICE/CED-3 inhibitors, YVAD-CHO and DEVD-CHO, were inactive in a cell-free system reconstituted from nuclei of untreated HL60 cells and cytosol from camptothecin-treated cells, suggesting that caspases are not required for endonuclease activation or lamin B cleavage in the cell-free system. By contrast, the serine protease inhibitors, 3,4-dichloroisocoumarin (DCl) and L-1-chloro-3-(4-tosylamido)4-phenyl-2-butanone tosyl-L-phenylalanine chloromethyl ketone (TPCK), abolished the apoptosis-associated biochemical changes induced by camptothecin both in whole cells and in a cell-free system. DCl also inhibited CPP32 cleavage. Taken together, these results suggest that in HL60 cells, both CPP32 and serine proteases are activated in camptothecin-induced apoptosis. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 54 TC 90 Z9 94 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 1997 VL 11 IS 8 BP 1238 EP 1244 DI 10.1038/sj.leu.2400734 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA XR625 UT WOS:A1997XR62500010 PM 9264376 ER PT J AU Alonsozana, ELC Stamberg, J Kumar, D Jaffe, ES Medeiros, LJ Frantz, C Schiffer, CA OConnell, BA Kerman, S Stass, SA Abruzzo, LV AF Alonsozana, ELC Stamberg, J Kumar, D Jaffe, ES Medeiros, LJ Frantz, C Schiffer, CA OConnell, BA Kerman, S Stass, SA Abruzzo, LV TI Isochromosome 7q: the primary cytogenetic abnormality in hepatosplenic gamma delta T cell lymphoma SO LEUKEMIA LA English DT Article DE T cell lymphoma; hepatosplenic lymphoma; isochromosome; chromosome 7 ID CLINICOPATHOLOGICAL ENTITY; GENE REARRANGEMENTS; NEOPLASMS; CHILDHOOD; DISEASE AB Malignant lymphomas often have complex, nonrandom chromosomal abnormalities. Hepatosplenic gamma delta T cell lymphoma (gamma delta TCL) is an unusual post-thymic T cell lymphoma that primarily involves river and spleen, often in young adult males. Few cases have had cytogenetic analysis. We report a consistent isochromosome 7q [i(7q)] abnormality in three cases of hepatosplenic gamma delta TCL, one with i(7q) as the sole abnormality at presentation. Three patients, 15-, 37- and 65-year-old males, presented with hepatosplenomegaly and fevers. Histopathologic, immunophenotypic, and molecular genetic studies supported the diagnosis. Spleen, liver, and bone marrow contained sinusoidal infiltrates of atypical lymphoid cells of T cell immunophenotype. PCR performed on two cases demonstrated clonal T cell receptor gamma gene rearrangements. Cytogenetic analysis of bone marrow showed i(7q) as the sole abnormality at presentation in one case. The second case showed i(7q) in addition to two normal chromosomes 7, and other structural and numerical abnormalities. The third case showed i(7q) and a deletion in the long arm of chromosome 11. These findings support the proposal that i(7q) represents the primary nonrandom cytogenetic abnormality in hepatosplenic gamma delta TCL, and plays a role in its pathogenesis. C1 UNIV MARYLAND,DEPT PATHOL,LABS PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,DIV HUMAN GENET,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT PEDIAT,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT MED,BALTIMORE,MD 21201. UNIV MARYLAND,MARLENE & STEWART GREENEBAUM CANC CTR,BALTIMORE,MD 21201. NCI,PATHOL LAB,HEMATOPATHOL SECT,NIH,BETHESDA,MD 20892. CITY HOPE NATL MED CTR,DIV PATHOL,DUARTE,CA 91010. AMER MED LABS,CHANTILLY,VA. NR 27 TC 64 Z9 67 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 1997 VL 11 IS 8 BP 1367 EP 1372 DI 10.1038/sj.leu.2400742 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA XR625 UT WOS:A1997XR62500028 PM 9264394 ER PT J AU Piez, KA AF Piez, KA TI History of extracellular matrix: A personal view SO MATRIX BIOLOGY LA English DT Article DE collagen; connective tissue; crosslinks; extracellular matrix; protein structure ID CARTILAGE COLLAGEN; HYDROXYPROLINE; SKIN AB Before the early 1800s, the ''fibers'' of connective tissue were thought to be the basis of life, which arose by spontaneous generation. With the discovery of cells in connective tissue, the cellular theory became accepted as the basis of life in about 1850. Material outside cells, but presumably made by cells, was recognized as the extracellular matrix. In the period from 1930 to 1975, the components of extracellular matrix were characterized by physical chemical, chemical and cell biological methods. For the major collagen of skin, tendon and bone, the molecular and fibril structures were determined; the aldehydederived crosslinks were discovered; its polypeptide chains were sequenced; and its biosynthesis and degradation were defined. This collagen, now type I collagen, was shown to be one of many types. The events of this period are described from the author's perspective. Since 1975, molecular and cell biological techniques have shown that the extracellular matrix is not the passive residence of cells but is highly interactive and plays a major role in health and disease. RP Piez, KA (reprint author), NIH,BLDG 30,ROOM 132,BETHESDA,MD 20892, USA. NR 39 TC 11 Z9 12 U1 1 U2 6 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD AUG PY 1997 VL 16 IS 3 BP 85 EP 92 DI 10.1016/S0945-053X(97)90037-8 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XW551 UT WOS:A1997XW55100001 PM 9314158 ER PT J AU Murray, D Precht, P Balakir, R Horton, W AF Murray, D Precht, P Balakir, R Horton, W TI Evidence for a role of E-box motifs in the regulation of type II collagen expression by chrondrocytes SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NIA,CTR GERONTOL RES,NIH,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD AUG PY 1997 VL 16 IS 3 BP 125 EP 125 DI 10.1016/S0945-053X(97)90055-X PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XW551 UT WOS:A1997XW55100019 ER PT J AU Adams, CS Tillman, S Horton, WE AF Adams, CS Tillman, S Horton, WE TI Murine articular cartilage apoptosis increases with age SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD AUG PY 1997 VL 16 IS 3 BP 129 EP 129 DI 10.1016/S0945-053X(97)90065-2 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XW551 UT WOS:A1997XW55100029 ER PT J AU Tockman, MS Mulshine, JL AF Tockman, MS Mulshine, JL TI Sputum screening by quantitative microscopy: A new dawn for detection of lung cancer? SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 NCI,DIV CLIN SCI,NIH,BETHESDA,MD 20892. RP Tockman, MS (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,615 N WOLFE ST,ROOM 7515,BALTIMORE,MD 21205, USA. NR 15 TC 15 Z9 15 U1 0 U2 2 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD AUG PY 1997 VL 72 IS 8 BP 788 EP 790 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA XR367 UT WOS:A1997XR36700015 PM 9276609 ER PT J AU Heymer, J Kuehn, M Ruther, U AF Heymer, J Kuehn, M Ruther, U TI The expression pattern of nodal and lefty in the mouse mutant Ft suggests a function in the establishment of handedness SO MECHANISMS OF DEVELOPMENT LA English DT Article DE left-right development; handedness; fused toes mutation; nodal; lefty ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; SITUS-INVERSUS; EMBRYOS; MICE; VG1 AB We have investigated the expression of left/right (L/R) asymmetry markers, nodal and lefty, in the situs inversus mouse mutant Fused foes (Ft). Both genes exhibited bilateral expression in the lateral plate mesoderm (LPM) at developmental stages whereas in wildtype embryos these genes were found to be expressed exclusively in the left LPM. Inspection of tail location and primitive heart tube looping, structures known to be handed in their orientation, documented a random orientation of these structures. Crossing of the Ft mutation into a different genetic background resulted in a strong reduction of this random orientation. Although the major fraction of these individuals still displayed nodal and lefty on both sides of the LPM, expression was almost always found to be weaker in the right LPM. These results suggest that the establishment of asymmetry is independent of nodal or lefty signals. However, handed asymmetry, which means consistent L/R differences, such as the dextral looping of the primitive heart tube or the right-oriented tail, is directed by differences in the L/R expression pattern of these two genes. (C) 1997 Elsevier Science Ireland Ltd. C1 HANNOVER MED SCH,INST MOL BIOL OE5250,D-30623 HANNOVER,GERMANY. NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 22 TC 50 Z9 51 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD AUG PY 1997 VL 66 IS 1-2 BP 5 EP 11 DI 10.1016/S0925-4773(97)00084-1 PG 7 WC Developmental Biology SC Developmental Biology GA XV576 UT WOS:A1997XV57600002 PM 9376323 ER PT J AU Lauderdale, DS Fabsitz, R Meyer, JM Sholinsky, P Ramakrishnan, V Goldberg, J AF Lauderdale, DS Fabsitz, R Meyer, JM Sholinsky, P Ramakrishnan, V Goldberg, J TI Familial determinants of moderate and intense physical activity: A twin study SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE Vietnam era twin registry; exercise; genetics; human; running; bicycling; swimming; racquet; sports ID PARTICIPATION; POPULATION; REGISTRY; PARENTS; WOMEN; LEVEL; MEN AB This twin study estimates familial clustering of moderate and intense leisure-time physical activity and investigates quantitatively its genetic and environmental components. Study subjects are 3,344 male twin pairs aged 33-51 yr. Moderate activity levels were assessed with six questions about discretionary walking or stair climbing for exercise. Five questions assessed regular participation in specific, intense athletic activities (running, bicycling, swimming, racquet, and other sports). Familial aggregation is estimated by odds ratios of one twin engaging in an activity when his co-twin does. Monozygotic and dizygotic twin correlations were compared to estimate genetic and nongenetic sources of phenotypic variation. For each activity, the familial aggregation odds ratio was statistically significant with values between 2.9 to 4.6 for intense activities and between 1.4 and 1.9 for all moderate activities but one. Monozygotic twin correlations were higher than dizygotic, suggesting genes play a role in the observed phenotypic variation. For four questions, and a composite scale of moderate activity, the difference between correlations was statistically significant (P < 0.05). In this cohort, much of the phenotypic variability for both moderate and intense activities is a result of familial effects. Genes may influence regular participation in specific intense exercises more than moderate activity, such as walking for exercise. C1 NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. DEPT VET AFFAIRS HOSP,CTR COOPERAT STUDIES HLTH SERV,VIETNAM ERA TWIN REGISTRY,HINES,IL. UNIV ILLINOIS,SCH PUBL HLTH,DIV EPIDEMIOL BIOSTAT,CHICAGO,IL. RP Lauderdale, DS (reprint author), UNIV CHICAGO,DEPT HLTH STUDIES,5841 S MARYLAND AVE,CHICAGO,IL 60637, USA. FU NIA NIH HHS [T32AGO0231] NR 25 TC 78 Z9 79 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD AUG PY 1997 VL 29 IS 8 BP 1062 EP 1068 DI 10.1097/00005768-199708000-00012 PG 7 WC Sport Sciences SC Sport Sciences GA XR035 UT WOS:A1997XR03500012 PM 9268964 ER PT J AU Mauras, N Vieira, NE Yergey, AL AF Mauras, N Vieira, NE Yergey, AL TI Estrogen therapy enhances calcium absorption and retention and diminishes bone turnover in young girls with Turner's syndrome: A calcium kinetic study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID VITAMIN-D METABOLISM; MINERAL METABOLISM; PREPUBERTAL GIRLS; WOMEN; DENSITY; CHILDREN; DETERMINANTS; HORMONE; PUBERTY; FEMALES AB Using stable tracers of calcium, we have previously shown a significant increase in calcium absorption and retention in prepubertal boys treated with exogenous testosterone. To investigate the effects of estrogen replacement on measures of calcium absorption, retention, and bone turnover, we studied a group of seven hypogonadal girls with Turner's syndrome (mean +/- SE age, 12.5 +/- 0.7 years). At baseline, Ca-42 intravenously (IV) and Ca-44 orally were administered, and blood and urine samples were collected for approximately 130 hours. Estrogen therapy was begun as ethinyl estradiol (4 or 20 mu g/d) or intramuscular depot estradiol given over 4 weeks, after which an identical study was repeated. Analysis of calcium enrichment in blood and urine was performed using mass spectrometry methods. After estrogen therapy, there was a significant increase in calcium absorption ([Va] P = .03) and total calcium retention ([Vbal] P = .04), similar to the effects of testosterone in boys. Bone accretion (Vo(+)) decreased after estrogen therapy (P = .004), as did resorption ([Vo(-)] P = .004). The overall rate of whole-body calcium turnover (Vt) was significantly decreased after estrogen administration (P = .04). These findings were opposite of those observed in prepubertal boys treated with testosterone. The contribution of bone resorption to whole-body turnover (E) also decreased after estrogen therapy (P = .05). These changes were associated with increased levels of 1,25-dihydroxyvitamin D after therapy with estrogens (P = .05). We conclude that estrogen supplementation is significantly anabolic for calcium metabolism by markedly increasing calcium absorption and retention and diminishing the estimated whole-body calcium turnover in girls with severe hypogonadism and Turner's syndrome. Further studies assessing the dietary calcium and/or vitamin D intake and bone mineral density of hypogonadal girls whose estrogen replacement is intentionally delayed will further define the need for calcium or vitamin D supplements in the peripubertal years in this condition. Copyright (C) 1997 by W.B. Saunders Company. C1 NICHHD, THEORET & PHYS BIOL LAB, BETHESDA, MD 20892 USA. RP Mauras, N (reprint author), NEMOURS CHILDRENS CLIN, 807 NIRA ST, JACKSONVILLE, FL 32207 USA. NR 37 TC 29 Z9 29 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 1997 VL 46 IS 8 BP 908 EP 913 DI 10.1016/S0026-0495(97)90078-0 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XP489 UT WOS:A1997XP48900010 PM 9258273 ER PT J AU Wehrly, K Chesebro, B AF Wehrly, K Chesebro, B TI p24 antigen capture assay for quantification of human immunodeficiency virus using readily available inexpensive reagents SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID HIV; IMMUNOASSAY; GENE AB Antigen capture enzyme-linked immunosorbent assay (ELISA) for quantitation of the p24 gag protein of human immunodeficiency virus type-1 (HIV-1) is currently the most common method used to demonstrate virus replication both in viva and in vitro. The present paper describes an ELISA employing readily available inexpensive reagents and gives detailed suggestions for optimizing The variables for specific purposes. The assay is as sensitive as commercial hits (25 pg/ml) and has a linear dose response over a wide range of p24 concentrations (25-1000 pg/ml). For these reasons, as well as its low cost, this assay has proven useful in a variety of research applications. This assay also has been found to be effective in detecting the gag protein of human immunodeficiency virus type-2 and simian immunodeficiency virus. (C) 1997 Academic Press. RP Wehrly, K (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,NIH,903 S 4TH,HAMILTON,MT 59840, USA. NR 10 TC 88 Z9 90 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 1046-2023 J9 METHODS JI Methods PD AUG PY 1997 VL 12 IS 4 BP 288 EP 293 DI 10.1006/meth.1997.0481 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT382 UT WOS:A1997XT38200002 PM 9245608 ER PT J AU Lee, FJS Patton, WA Lin, CY Moss, J Vaughan, M Goldman, ND Syin, C AF Lee, FJS Patton, WA Lin, CY Moss, J Vaughan, M Goldman, ND Syin, C TI Identification and characterization of an ADP-ribosylation factor in Plasmodium falciparum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; erythrocyte; endoplasmic reticulum ID BREFELDIN-A; PHOSPHOLIPASE-D; BINDING PROTEIN; GOLGI MEMBRANES; CHOLERA-TOXIN; ARF PROTEIN; GTP; LOCALIZATION; ACTIVATION; SECRETION C1 NATL TAIWAN UNIV,SCH MED,INST MOL MED,TAIPEI 10764,TAIWAN. NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. OI LEE, FANG-JEN/0000-0002-2167-2426 NR 38 TC 9 Z9 9 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 AUG PY 1997 VL 87 IS 2 BP 217 EP 223 DI 10.1016/S0166-6851(97)00061-3 PG 7 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA XL350 UT WOS:A1997XL35000010 PM 9247933 ER PT J AU Marton, MJ deAldana, CRV Qiu, HF Chakraburtty, K Hinnebusch, AG AF Marton, MJ deAldana, CRV Qiu, HF Chakraburtty, K Hinnebusch, AG TI Evidence that GCN1 and GCN20, translational regulators of GCN4, function on elongating ribosomes in activation of eIF2 alpha kinase GCN2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID VACUOLAR-MEMBRANE VESICLES; AMINO-ACID AVAILABILITY; RNA-BINDING PROTEIN; SACCHAROMYCES-CEREVISIAE; FACTOR-III; SHUTTLE VECTORS; YEAST; GENE; INITIATION; CONSTRUCTION AB In the yeast Saccharomyces cerevisae, phosphorylation of translation initiation factor eIF2 by protein kinase GCN2 leads to increased translation of the transcriptional activator GCN4 in amino acid-starved cells. The GCN1 and GCN20 proteins are components of a protein complex required for the stimulation of GCN2 kinase activity under starvation conditions, GCN20 is a member of the ATP-binding cassette (ABC) family, most of the members of which function as membrane-bound transporters, raising the possibility that the GCN1/GCN20 complex regulates GCN2 indirectly as an amino acid transporter. At odds with this idea, indirect immunofluorescence revealed cytoplasmic localization of GCN1 and no obvious association with plasma or vacuolar membranes. In addition, a fraction of GCN1 and GCN20 cosedimented with polysomes and 80S ribosomes, and the ribosome association of GCN20 was largely dependent on GCN1. The C-terminal 84% of GCN20 containing the ABCs was found to be dispensable for complex formation with GCN1 and for the stimulation of GCN2 kinase function. Because ABCs provide the energy-coupling mechanism for ABC transporters, these results also contradict the idea that GCN20 regulates GCN2 as an amino acid transporter. The N-terminal 15 to 25% of GCN20, which is critically required for its regulatory function, was found to interact with an internal segment of GCN1 similar in sequence to translation elongation factor 3 (EF3). Based on these findings, we propose that GCN1 performs an EM-related function in facilitating the activation of GCN2 by uncharged tRNA on translating ribosomes. The physical interaction between GCN20 and the EF3-like domain in GCN1 could allow for modulation of GCN1 activity, and the ABC domains in GCN20 may be involved in this regulatory function. A human homolog of GCN1 has been identified, and the portion of this protein most highly conserved with yeast GCN1 has sequence similarity to EF3. Thus, similar mechanisms for the detection of uncharged tRNA on translating ribosomes may operate in yeast and human cells. C1 NICHHD, LAB EUKARYOT GENE REGULAT, BETHESDA, MD 20892 USA. MED COLL WISCONSIN, DEPT BIOCHEM, MILWAUKEE, WI 53226 USA. RI Vazquez de Aldana, Carlos/B-7772-2008 OI Vazquez de Aldana, Carlos/0000-0002-4513-3654 NR 54 TC 107 Z9 111 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1997 VL 17 IS 8 BP 4474 EP 4489 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XM783 UT WOS:A1997XM78300029 PM 9234705 ER PT J AU Zhang, SR Burkett, TJ Yamashita, I Garfinkel, DJ AF Zhang, SR Burkett, TJ Yamashita, I Garfinkel, DJ TI Genetic redundancy between SPT23 and MGA2: Regulators of Ty-induced mutations and Ty1 transcription in Saccharomyces cerevisiae SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SNF6 PROTEINS; YEAST; EXPRESSION; ACTIVATION; GAL4; DNA; RETROTRANSPOSITION; TRANSFORMATION; CONSTRUCTION; MUTAGENESIS AB SPT23 was isolated as a dosage-dependent suppressor of Ty-induced mutations in Saccharomyces cerevisiae. SPT23 shows considerable sequence homology with MGA2, a gene identified as a dosage-dependent suppressor of a snf2-imposed block on STA1 transcription in S. cerevisiae var. diastaticus. Although single mutations in either of these genes have only modest effects on cell growth, spt23 mga2 double mutants are inviable. Unlike SPT23, multicopy expression of a truncated form of MGA2 suppresses a narrow subset of Ty-induced mutations. SPT23/MGA2 and the SNF/SWI genes affect transcription of certain target genes in similar ways, Spt23p appears to be a rate-limiting component required for functional HIS4 expression of his4-912 delta, a promoter insertion mutation induced by the Tyl-912 long terminal repeat, Furthermore, both Spt23p and Mga2p can activate transcription when fused to the Gal4p DNA-binding domain, as previously observed with Snf2p and Snf5p. A 50-amino-acid region in the N terminus of the predicted Spt23p protein is necessary and sufficient for the transactivation and necessary for suppression of Ty1-induced mutations and the essential function of Spt23p. Cell fractionation and cytological experiments suggest that Spt23p is associated with the nucleus. Our results suggest that SPT23/MGA2 affects transcription of a subset of genes in yeast, perhaps by changing chromatin accessibility. C1 NCI, GENE REGULAT & CHROMOSOME BIOL LAB, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. HIROSHIMA UNIV, CTR GENE SCI, HIGASHIHIROSHIMA 724, JAPAN. NR 65 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1997 VL 17 IS 8 BP 4718 EP 4729 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XM783 UT WOS:A1997XM78300052 PM 9234728 ER PT J AU Puzianowska-Kuznicka, M Damjanovski, S Shi, YB AF Puzianowska-Kuznicka, M Damjanovski, S Shi, YB TI Both thyroid hormone and 9-cis retinoic acid receptors are required to efficiently mediate the effects of thyroid hormone on embryonic development and specific gene regulation in Xenopus laevis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; C-ERBA-ALPHA; AMPHIBIAN METAMORPHOSIS; NUCLEAR RECEPTOR; TRANSCRIPTIONAL ACTIVATION; POSTEMBRYONIC DEVELOPMENT; ONCOGENE PRODUCT; RESPONSE ELEMENT; AXIS FORMATION; X RECEPTORS AB Tissue culture transfection and in vitro biochemical studies have suggested that heterodimers of thyroid hormone receptors (TRs) and 9-cis retinoic acid receptors (RXRs) are the likely in vivo complexes that mediate the biological effects of thyroid hormone, 3,5,3'-triiodothyronine (T-3). However, direct in vivo evidence for such a hypothesis has been lacking. We have previously reported a close correlation between the coordinated expression of TR and RXR genes and tissue-dependent temporal regulation of organ transformations during Xenopus laevis metamorphosis. By introducing TRs and RXRs either individually or together into developing Xenopus embryos, we demonstrate here that RXRs are critical for the developmental function of TRs, Precocious expression of TRs and RXRs together but not individually leads to drastic, distinct embryonic abnormalities, depending upon the presence or absence of T-3, and these developmental effects require the same receptor domains as those required for transcriptional regulation by TR-RXR heterodimers. More importantly, the overexpressed TR-RXR heterodimers faithfully regulate endogenous T-3 response genes that are normally regulated by T-3 only during metamorphosis. That is, they repress the genes in the absence of T-3 and activate them in the presence of the hormone. On the other hand, the receptors have no effect on a retinoic acid (RA) response gene. Thus, RA- and T-3 receptor-mediated teratogenic effects in Xenopus embryos occur through distinct molecular pathways, even though the resulting phenotypes have similarities. C1 NICHHD, MOL EMBRYOL LAB, NIH, BETHESDA, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 78 TC 67 Z9 67 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1997 VL 17 IS 8 BP 4738 EP 4749 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XM783 UT WOS:A1997XM78300054 PM 9234730 ER PT J AU Topol, LZ Marx, M Laugier, D Bogdanova, NN Boubnov, NV Clausen, PA Calothy, G Blair, DG AF Topol, LZ Marx, M Laugier, D Bogdanova, NN Boubnov, NV Clausen, PA Calothy, G Blair, DG TI Identification of drm, a novel gene whose expression is suppressed in transformed cells and which can inhibit growth of normal but not transformed cells in culture SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RAT FIBROBLASTS; BCL-2 PROTEINS; SARCOMA-VIRUS; DAN GENE; V-MOS; TUMOR; CDNA; DNA; SRC; DIFFERENTIATION AB Using differential display analysis, we compared the expression of RNA in v-mos-transformed cells and their flat revertant and isolated a novel gene, drm (down-regulated in mos-transformed cells), whose expression is down-regulated in parental v-mos-transformed cells but which is expressed at a high level in the revertant and normal rat fibroblasts (REF-1 cells), Analysis of different oncogene-transformed cells revealed that drm gene expression was also suppressed in REF-1 cells transformed by v-ras, v-src, v-raf, and v-fos, The drm cDNA contains a 184-amino-acid-protein-encoding open reading frame which shows no significant homologies to known genes in DNA databases, Polyclonal antibodies raised against drm peptide detect a protein with the predicted size of 20.7 kDa in normal cells and under nonpermissive conditions in cells conditionally transformed by v-mos but not in parental v-mos-transformed cells, Northern analysis of normal adult tissues shows that drm is expressed as a 4,4-kb message in a tissue-specific manner, with high expression in the brain, spleen, kidney, and testis and little or no expression in the heart, liver, and skeletal muscle. In situ hybridization analysis in adult rat tissue reveals good correlation with this pattern and indicates that drm mRNA is most highly expressed in nondividing and terminally differentiated cells, such as neurons, type 1 lung cells, and goblet cells, Transfection of a drug-selectable drm expression vector dramatically reduced the efficiency of colony formation in REF-1 and CHO cells, and the drm-transfected REF-1 survivors expressed low or nondetectable levels of exogenous drm mRNA, The toxic effects of drm can he overcome by cotransfection with constructs expressing oncogenic ras; furthermore, cells expressing high levels of drm and conditionally transformed with mos-expressing Moloney murine sarcoma virus rapidly undergo apoptosis when shifted to the nonpermissive temperature, Taken together, our data suggest that cells expressing high levels of drm undergo apoptotic death in the absence of oncogene-induced transformation and that drm represents a novel gene with potential roles in cell growth control or viability and tissue-specific differentiation. C1 NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FCRDC,FREDERICK,MD 21702. NCI,BASIC RES LAB,DIV BASIC SCI,FREDERICK,MD 21702. CTR UNIV ORSAY,INST CURIE,CNRS,UNITE MIXTE RECH 146,F-91405 ORSAY,FRANCE. ST LOUIS UNIV,ST LOUIS,MO 63104. NR 44 TC 91 Z9 94 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1997 VL 17 IS 8 BP 4801 EP 4810 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XM783 UT WOS:A1997XM78300060 PM 9234736 ER PT J AU Ogryzko, VV Wong, P Howard, BH AF Ogryzko, VV Wong, P Howard, BH TI WAF1 retards S-phase progression primarily by inhibition of cyclin-dependent kinases SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SMALL-T-ANTIGEN; CELL NUCLEAR ANTIGEN; PROTEIN PHOSPHATASE-2A; DNA-REPLICATION; SIMIAN VIRUS-40; POTENTIAL MEDIATOR; TUMOR-ANTIGENS; CDK; GROWTH; P21 AB The p(2WAF1/CIP1/sdi1) gene product (WAF1) inhibits DNA replication in vitro (J. Chen, P. Jackson, M. Kirschner, and A. Dutta, Nature 374:386-388, 1995; S. Waga, G. Hannon, D. Beach, and B. Stillman, Nature 369:574-578, 1994), but in vivo studies on the antiproliferative activity of WAF1 have not resolved G(1)-phase arrest from potential inhibition of S-phase progression. Here, we demonstrate that elevated WAF1 expression can retard replicative DNA synthesis in vivo. The WAF1-mediated inhibitory effect could be antagonized by cyclin A, cyclin E, or the simian virus 40 small-t antigen with no decrease in the levels of WAF1 protein in transfected cells, Proliferating-cell nuclear antigen (PCNA) overexpression was neither necessary nor sufficient to antagonize WAF1 action, Expression of the N-terminal domain of WAF1, responsible for cyclin-dependent kinase (CDK) interaction, had the same effect as full-length WAF1, while the PCNA binding C terminus exhibited modest activity. We conclude that S-phase progression in mammalian cells is dependent on continuing cyclin and CDK activity and that WAF1 affects S phase primarily through cyclin- and CDK-dependent pathways. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 40 TC 156 Z9 158 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1997 VL 17 IS 8 BP 4877 EP 4882 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XM783 UT WOS:A1997XM78300068 PM 9234744 ER PT J AU Carrington, M Stephens, JC Ma, WY Martin, M Harding, A Noble, J Erlich, H Mann, D Arango, C Jaramillo, R Concha, M Maloney, E Blattner, W AF Carrington, M Stephens, JC Ma, WY Martin, M Harding, A Noble, J Erlich, H Mann, D Arango, C Jaramillo, R Concha, M Maloney, E Blattner, W TI Identification of a novel TAP2 allele in a Colombian black population: Gene conversion, ancestral intermediate, or convergent change? SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Letter DE HLA; TAP2; gene conversion; molecular evolution ID CLASS-II REGION; MAJOR HISTOCOMPATIBILITY COMPLEX; LINKAGE DISEQUILIBRIUM; POLYMORPHISM; VARIANTS; PROBES; DNA C1 SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. ROCHE MOL SYST,DEPT HUMAN GENET,ALAMEDA,CA. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. UNIV VALLE,CALI,COLOMBIA. UNIV MIAMI,DEPT NEUROL,CORAL GABLES,FL 33124. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. UNIV MARYLAND,DEPT MED,BALTIMORE,MD 21201. RP Carrington, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,POB B,FREDERICK,MD 21702, USA. NR 13 TC 2 Z9 2 U1 1 U2 2 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD AUG PY 1997 VL 14 IS 8 BP 892 EP 894 PG 3 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA XP204 UT WOS:A1997XP20400014 PM 9254928 ER PT J AU Hennighausen, L AF Hennighausen, L TI Molecular mechanisms of hormone controlled gene expression in the breast SO MOLECULAR BIOLOGY REPORTS LA English DT Article ID ACIDIC PROTEIN GENE; TISSUE PLASMINOGEN-ACTIVATOR; MAMMARY EPITHELIAL-CELLS; TRANSGENIC MICE; TRANSCRIPTION FACTOR; NUCLEAR FACTOR; DNA-BINDING; PROMOTER; GLAND; MILK AB In a meritorious effort H. de Rothschild compiled in 1899 all publications on mammary gland development and milk -a grand total of 8375 [1]. In the preface to this publication Duclaux states: 'Such a discrepancy between the tremendous efforts and the paltriness of the results -hundreds of scientists and thousands of research years, just to create 200 or 300 pages of truth'. The number of papers added since then must be enormous. Rather than reviewing a vast literature, I will take the liberty and focus on research which, in my opinion, shaped our understanding of hormone controlled gene expression in the developing breast. RP Hennighausen, L (reprint author), NIDDK,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892, USA. NR 43 TC 11 Z9 13 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0301-4851 J9 MOL BIOL REP JI Mol. Biol. Rep. PD AUG PY 1997 VL 24 IS 3 BP 169 EP 174 DI 10.1023/A:1006851531360 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XU384 UT WOS:A1997XU38400003 PM 9291090 ER PT J AU Chodobski, A Loh, YP Corsetti, S SzmydyngerChodobska, J Johanson, CE Lim, YP Monfils, PR AF Chodobski, A Loh, YP Corsetti, S SzmydyngerChodobska, J Johanson, CE Lim, YP Monfils, PR TI The presence of arginine vasopressin and its mRNA in rat choroid plexus epithelium SO MOLECULAR BRAIN RESEARCH LA English DT Article DE arginine vasopressin; choroid plexus; immunohistochemistry; hybridization histochemistry, in situ; rat ID CEREBROSPINAL-FLUID; NERVOUS-SYSTEM; ANGIOTENSIN-II; MESSENGER-RNA; 3RD VENTRICLE; SUBSTANCE-P; RELEASE; EXPRESSION; OXYTOCIN; BRAIN AB Arginine vasopressin (AVP) plays an important role in the regulation of secretory function and hemodynamics of choroid plexus, the primary site of cerebrospinal fluid (CSF) production. in the present study, localization of AVP and its transcripts in choroid plexus of adult male Sprague-Dawley rats was studied by immunohistochemistry and in situ hybridization histochemistry, respectively. For immunohistochemical analysis, AVP-specific polyclonal rabbit antibody was employed. Plasmid, pGrVP, containing a 232-bp fragment of rat AVP cDNA encoding the C-terminus of proAVP, was used as a probe to detect AVP mRNA. AVP-immunoreactive product was predominantly localized close to the apical (CSF-facing) membrane of choroidal epithelium while AVP transcripts were distributed throughout the cytoplasm of the cells. Our findings indicate that AVP is synthesized in choroid plexus epithelium, which suggests autocrine and/or paracrine actions of this peptide in choroidal tissue. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,NIH,BETHESDA,MD 20892. BROWN UNIV,RHODE ISL HOSP,DEPT MED,PROVIDENCE,RI 02903. BROWN UNIV,RHODE ISL HOSP,CENT RES LABS,PROVIDENCE,RI 02903. RP Chodobski, A (reprint author), BROWN UNIV,RHODE ISL HOSP,DEPT CLIN NEUROSCI,PROGRAM NEUROSURG,ALDRICH BLDG,ROOM 403,593 EDDY ST,PROVIDENCE,RI 02903, USA. NR 34 TC 37 Z9 37 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 AUG PY 1997 VL 48 IS 1 BP 67 EP 72 DI 10.1016/S0169-328X(97)00079-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA XM885 UT WOS:A1997XM88500010 ER PT J AU Hirata, H Cadet, JL AF Hirata, H Cadet, JL TI Kainate-induced hippocampal DNA damage is attenuated in superoxide dismutase transgenic mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE kainic acid; transgenic mice; superoxide dismutase; free radical; hippocampus; nick translation; in situ ID KAINIC ACID; RAT; EXCITOTOXICITY; NEUROTOXICITY; MECHANISMS; NEURONS AB Peripheral administration of kainic acid (KA) can cause cell death in the hippocampus of rodents. This is thought to involve oxidative stress. In the present study, we tested the possibility that KA-induced neuronal cell death might be attenuated in CuZn superoxide dismutase transgenic (SOD-Tg) mice. Acute administration of KA causes animal death in a dose-dependent fashion; this was attenuated in SOD-Tg mice. Similarly, KA caused dose-dependent neuronal cell death in the hippocampus of wild-type mice; this cell death was attenuated in the SOD-Tg mice, in a gene-dosage-dependent fashion, with homozygous mice showing complete protection even at the highest dose (45 mg/kg) of KA used in this study. These results provide further support for the involvement of oxygen-based radicals in the toxic effects of KA. C1 NIDA,MOL NEUROPSYCHIAT SECT,NIH,DIV INTRAMURAL RES,BALTIMORE,MD 21224. NR 19 TC 32 Z9 32 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 AUG PY 1997 VL 48 IS 1 BP 145 EP 148 DI 10.1016/S0169-328X(97)00121-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA XM885 UT WOS:A1997XM88500019 ER PT J AU Shiao, YH Diwan, BA Perantoni, AO Calvert, RJ Zbar, B Lerman, MI Rice, JM AF Shiao, YH Diwan, BA Perantoni, AO Calvert, RJ Zbar, B Lerman, MI Rice, JM TI Polymerase chain reaction single-strand conformation polymorphism analysis for the VHL gene in chemically induced kidney tumors of rats using intron-derived primers SO MOLECULAR CARCINOGENESIS LA English DT Article DE von Hippel-Lindau gene; introns; rat kidney tumors ID RENAL-CELL CARCINOMA; HIPPEL-LINDAU DISEASE; SUPPRESSOR GENE; SOMATIC MUTATIONS; K-RAS; DIMETHYLNITROSAMINE; PHENOTYPE; PATHOLOGY; CLONING; HOMOLOG AB von Hippel-Lindau (VHL) gene mutations occur throughout three exons including the exon-intron boundaries in human VHL disease-associated and sporadic renal cell carcinomas. To explore the possible role of the VHL gene in chemically induced rat kidney tumors originating from various cell types, more than 150 bp of Fischer 344 and Noble rat VHL intron sequences flanking the three exons was determined by dideoxy sequencing. Five primer sets were selected for polymerase chain reaction amplification of the coding regions of rat VHL exons 1-3 and the exon-intron boundaries. Tissues from 10 renal eosinophilic epithelial tumors induced by N-nitrosoethyl(2-hydroxyethyl)amine, 10 nephroblastomas induced by N-nitroso-N-ethylurea, and seven renal mesenchymal tumors induced by N-nitrosomethyl(methoxymethyl)amine were examined for VHL mutations by polymerase chain reaction-single-strand conformation polymorphism analysis. No mutation was detected in any tumor type, indicating that VHL mutations are not involved in the pathogenesis of rat kidney tumors arising from the distal region of the renal tubules, the metanephric blastema, or stromal tissues of the cortex. (C) 1997 Wiley-Liss. Inc. C1 SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. US FDA,CTR FOOD SAFETY & APPL NUTR,OFF SPECIAL NUTR,LAUREL,MD. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. INT AGCY RES CANC,UNIT CARCINOGEN IDENTIFICAT & EVALUAT,F-69372 LYON,FRANCE. RP Shiao, YH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. NR 31 TC 12 Z9 12 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 1997 VL 19 IS 4 BP 230 EP 235 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XU105 UT WOS:A1997XU10500003 PM 9290699 ER PT J AU Couse, JF Davis, VL Hanson, RB Jefferson, WN McLachlan, JA Bullock, BC Newbold, RR Korach, KS AF Couse, JF Davis, VL Hanson, RB Jefferson, WN McLachlan, JA Bullock, BC Newbold, RR Korach, KS TI Accelerated onset of uterine tumors in transgenic mice with aberrant expression of the estrogen receptor after neonatal exposure to diethylstilbestrol SO MOLECULAR CARCINOGENESIS LA English DT Article DE carcinogenesis; adenocarcinoma; steroid receptors ID EPIDERMAL GROWTH-FACTOR; HUMAN BREAST-CANCER; MOUSE UTERUS; PROGNOSTIC FACTORS; MESSENGER-RNA; FEMALE MOUSE; ADENOCARCINOMA; ER; PROLIFERATION; DISRUPTION AB The role of estrogen and the estrogen receptor (ER) in the induction and promotion of tumors was investigated by using transgenic MT-mER mice, which overexpress the ER. It was hypothesized that because of this abnormal expression of the ER, the reproductive-tract tissues of the MT-mER mice may be more susceptible to tumors after neonatal exposure to the potent synthetic estrogen diethylstilbestrol (DES). Normally non-estrogen responsive tissues that may have expressed ER as a result of the transgene were also studied for DES-induced tumors. Wild-type and MT-mER littermates were treated with 2 mu g/pup/d DES 1-5 d after birth and then killed at 4, 8, 12, and 18 mo of age. The DES-treated MT-mER mice demonstrated a significantly higher incidence of uterine adenocarcinoma at 8 mo (73%) than the DES-treated wild-type mice (46%). The tumors of the MT-mER mice were often more aggressive than those in the wild-type animals. These tumors were also preceeded at 4 mo by a significantly higher incidence of the preneoplastic lesion atypical hyperplasia in the MT-mER mice (26% compared with 0% in the wild-type mice). Other DES-induced abnormalities were observed at equal rates in the wild-type and MT-mER mice. Although no tumors were observed in untreated wildtype females, a single untreated MT-mER female had uterine adenocarcinoma at 18 mo. These data indicate that the level of ER present in a tissue may also be a determining factor in development of estrogen-responsive tumors. (C) 1997 Wiley-Liss. Inc. C1 NIEHS, RECEPTOR BIOL SECT, REPROD & DEV TOXICOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. NIEHS, DEV ENDOCRINOL & PHARMACOL SECT, REPROD TOXICOL GRP, SYST TOXICOL LAB, RES TRIANGLE PK, NC 27709 USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT COMPARAT MED, WINSTON SALEM, NC 27103 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 46 TC 57 Z9 59 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 1997 VL 19 IS 4 BP 236 EP 242 DI 10.1002/(SICI)1098-2744(199708)19:4<236::AID-MC4>3.0.CO;2-A PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XU105 UT WOS:A1997XU10500004 PM 9290700 ER PT J AU Packenham, JP duManoir, S Schrock, E Risinger, JI Dixon, D Denz, DN Evans, JAC Berchuck, A Barrett, JC Devereux, TR Ried, T AF Packenham, JP duManoir, S Schrock, E Risinger, JI Dixon, D Denz, DN Evans, JAC Berchuck, A Barrett, JC Devereux, TR Ried, T TI Analysis of genetic alterations in uterine leiomyomas and leiomyosarcomas by comparative genomic hybridization SO MOLECULAR CARCINOGENESIS LA English DT Article DE leiomyoma; comparative genomic hybridization; uterine tumors; sarcomas; molecular cytogenetics ID CHROMOSOME-ABERRATIONS; INSITU HYBRIDIZATION; CYTOGENETIC ANALYSIS; SOLID TUMORS; REARRANGEMENTS; PATTERNS; SARCOMAS; PROFILE; LOSSES; GAINS AB Uterine leiomyomas are the most prevalent tumor type in women of reproductive age and are the most common reason for hysterectomies. Although uterine leiomyomas are considered to be benign, they are a major public health concern for women. In contrast, leiomyosarcomas are rare but highly malignant uterine tumors. They may a rise in uteri with preexisting leiomyomas and histologically sometimes resemble leiomyomas, thus causing controversy about whether leiomyosarcomas arise within leiomyomas. In this study, we used comparative genomic hybridization (CGH) to identify genetic alterations unique to each tumor type and alterations that are common between the two tumors. We analyzed 14 cases of uterine leiomyomas and eight cases of uterine leiomyosarcomas. Only two of the 14 leiomyomas exhibited genetic alterations, and those were restricted to gains on chromosomes 14 and 19 and losses on chromosomes 1 and 4. In addition, 68 leiomyomas were examined for loss of heterozygosity on chromosomes 1 and 4, and only three tumors exhibited any losses. In contrast, all eight leiomyosarcomas showed gains and losses of DNA by CCH, and in many cases multiple changes were observed. The most commonly observed genetic aberration, occurring in five tumors, was gains on both arms of chromosome 1,suggesting that this chromosome contains loci involved in the development of leiomyosarcoma. Our results do not provide evidence for the progression from benign leiomyoma to malignant leiomyosarcoma. Moreover, the large number of random chromosomal alterations in the leiomyosarcomas suggests that increased genetic instability plays a role in the formation of these tumors. (C) 1997 Wiley-Liss. Inc. C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,LAB EXPT PATHOL,RES TRIANGLE PK,NC 27709. NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,NIH,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. NR 29 TC 47 Z9 48 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 1997 VL 19 IS 4 BP 273 EP 279 DI 10.1002/(SICI)1098-2744(199708)19:4<273::AID-MC9>3.0.CO;2-D PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XU105 UT WOS:A1997XU10500009 PM 9290705 ER PT J AU Arora, KK Cheng, ZY Catt, KJ AF Arora, KK Cheng, ZY Catt, KJ TI Mutations of the conserved DRS motif in the second intracellular loop of the gonadotropin-releasing hormone receptor affect expression, activation, and internalization SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; ANGIOTENSIN-II RECEPTOR; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; RAT PITUITARY; GNRH RECEPTOR; AMINO-ACIDS; FUNCTIONAL-CHARACTERIZATION; BETA-2-ADRENERGIC RECEPTOR AB The GnRH receptor is an unusual member of the G protein-coupled receptor (GPCR) superfamily with several unique features. One of these is a variant of the conserved DRY motif that is located at the junction of the third transmembrane domain and the second intracellular (2i) loop of most GPCRs. In the GnRH receptor, the Tyr residue of the conserved triplet is replaced by Ser, giving a DRS sequence. The aspartate and arginine residues of the triplet are highly conserved in almost all GPCRs. The functional importance of these residues was evaluated in wild type and mutant GnRH receptors expressed in COS-7 cells. Mutants in which Asp(138) was replaced by Asn or Glu were poorly expressed, but showed significantly increased internalization and exhibited augmented inositol phosphate generation to maximal agonist stimulation compared with the wild type receptor. In contrast, receptors in which Arg(139) was substituted With Gin, Ala, or Ser showed reduced internalization, and the GnRH-induced inositol phosphate response for the Arg(139)Gln mutant was significantly impaired in proportion to its low expression lever. Replacing Ser(140) with Ala affected neither internalization nor signal transduction. The role of the polar amino acids at the C terminus of the 2i loop was evaluated in two additional mutants (Ser(151)Ala, Ser(153)Ala, and Ser(151)Ala, Ser(153)Ala, Lys(154)Gln, Glu(156)Gln). Both of these mutants exhibited agonist-induced inositol phosphate responses similar to that of the wild type receptor, but showed increased receptor internalization. This mutational analysis indicates that the conserved Asp and Arg residues in the DRY/S triplet make important contributions to the structural integrity of the receptor and influence receptor expression, agonist-induced activation, and internalization. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, NIH, BETHESDA, MD 20892 USA. RI xu, tao/K-6631-2016 NR 53 TC 96 Z9 98 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 AUG PY 1997 VL 11 IS 9 BP 1203 EP 1212 DI 10.1210/me.11.9.1203 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XN623 UT WOS:A1997XN62300002 PM 9259312 ER PT J AU Padlan, EA AF Padlan, EA TI Does base composition help predispose the complementarity-determining regions of antibodies to hypermutation? SO MOLECULAR IMMUNOLOGY LA English DT Article DE somatic hypermutation; base usage bias; base pair mismatches ID SOMATIC HYPERMUTATION; IMMUNOGLOBULIN GENES; IMMUNE-RESPONSE; SEQUENCES; MUTATION; REPERTOIRE; ANTIGEN; INTRON; KAPPA; HYPERMUTAGENESIS AB A survey of the base usage in genes coding for human antibodies reveals that more (A+T) and less (C + G) are found in the segments coding for the complementarity-determining regions, while the opposite is true for the segments coding for framework and constant regions. The possibility that this bias in base usage may contribute to hypermutation is explored. Published by Elsevier Science Ltd. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Padlan, EA (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 303, Bethesda, MD 20892 USA. NR 36 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 1997 VL 34 IS 11 BP 765 EP 770 DI 10.1016/S0161-5890(97)00074-6 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA YP369 UT WOS:000071270000002 PM 9444975 ER PT J AU Koonin, EV Mushegian, AR Galperin, MY Walker, DR AF Koonin, EV Mushegian, AR Galperin, MY Walker, DR TI Comparison of archaeal and bacterial genomes: computer analysis of protein sequences predicts novel functions and suggests a chimeric origin for the archaea SO MOLECULAR MICROBIOLOGY LA English DT Article ID TRANSFER-RNA SYNTHETASES; YEAST CHROMOSOME-III; HAEMOPHILUS-INFLUENZAE; ESCHERICHIA-COLI; NUCLEOTIDYLTRANSFERASE SUPERFAMILY; KANAMYCIN NUCLEOTIDYLTRANSFERASE; EUKARYOTIC CELL; EVOLUTION; SIMILARITY; DATABASES AB Protein sequences encoded in three complete bacterial genomes, those of Haemophilus influenzae, Mycoplasma genitalium and Synechocystis sp., and the first available archaeal genome sequence, that of Methanococcus jannaschii, were analysed using the BLAST2 algorithm and methods for amino acid motif detection. Between 75% and 90% of the predicted proteins encoded in each of the bacterial genomes and 73% of the M, jannaschii proteins showed significant sequence similarity to proteins from other species. The fraction of bacterial and archaeal proteins containing regions conserved over long phylogenetic distances is nearly the same and close to 70%, Functions of 70-85% of the bacterial proteins and about 70% of the archaeal proteins were predicted with varying precision. This contrasts with the previous report that more than half of the archaeal proteins have no homologues and shows that, with more sensitive methods and detailed analysis of conserved motifs, archaeal genomes become as amenable to meaningful interpretation by computer as bacterial genomes. The analysis of conserved motifs resulted in the prediction of a number of previously undetected functions of bacterial and archaeal proteins and in the identification of novel protein families. In spite of the generally high conservation of protein sequences, orthologues of 25% or less of the IM. jannaschii genes were detected in each individual completely sequenced genome, supporting the uniqueness of archaea as a distinct domain of life. About 53% of the M. jannaschii proteins belong to families of paralogues, a fraction similar to that in bacteria with larger genomes, such as Synechocystis sp, and Escherichia coli, but higher than that in H. influenzae, which has approximately the same number of genes as M. jannaschii. Certain groups of proteins, e.g. molecular chaperones and DNA repair enzymes, thought to be ubiquitous and represented in the minimal gene set derived by bacterial genome comparison, are missing in M. jannaschii, indicating massive non-orthologous displacement of genes responsible for essential functions. An unexpectedly large fraction of the nn. jannaschii gene products, 44%, shows significantly higher similarity to bacterial than to eukaryotic proteins, compared with 13% that have eukaryotic proteins as their closest homologues (the rest of the proteins show approximately the same level of similarity to bacterial and eukaryotic homologues or have no homologues), Proteins involved in translation, transcription, replication and protein secretion are most closely related to eukaryotic proteins, whereas metabolic enzymes, metabolite uptake systems, enzymes for cell wall biosynthesis and many uncharacterized proteins appear to be 'bacterial'. A similar prevalence of proteins of apparent bacterial origin was observed among the currently available sequences from the distantly related archaeal genus, Sulfolobus. It is likely that the evolution of archaea included at least one major merger between ancestral cells from the bacterial lineage and the lineage leading to the eukaryotic nucleocytoplasm. C1 JOHNS HOPKINS UNIV, DEPT BIOL, BALTIMORE, MD 21218 USA. RP Koonin, EV (reprint author), NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, NIH, BETHESDA, MD 20894 USA. RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Mushegian, Arcady/0000-0002-6809-9225 NR 80 TC 236 Z9 238 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 1997 VL 25 IS 4 BP 619 EP 637 DI 10.1046/j.1365-2958.1997.4821861.x PG 19 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA XV850 UT WOS:A1997XV85000001 PM 9379893 ER PT J AU Colello, RJ Pott, U AF Colello, RJ Pott, U TI Signals that initiate myelination in the developing mammalian nervous system SO MOLECULAR NEUROBIOLOGY LA English DT Review DE oligodendrocyte; Schwann cell; glia; saltatory conduction; myelin; electrical activity; axon caliber; development; differentiation ID RAT OPTIC-NERVE; TRANSCRIPTION FACTOR SCIP; CULTURED SCHWANN-CELLS; MESSENGER-RNA EXPRESSION; ZINC-FINGER GENE; PROGENITOR CELLS; GROWTH-FACTORS; OLIGODENDROCYTE DIFFERENTIATION; ADHESION MOLECULES; BASIC-PROTEIN AB The myelination of axons by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system is essential for the establishment of saltatory conduction. Ln the absence or destruction of the myelin sheath, as seen in demyelinating diseases, impulse conduction is impeded resulting in severe sensory and motor deficits. Axon myelination is the culmination of a sequence of events that begins with the differentiation of glial cells and proceeds to the transcription and translation of myelin genes, the elaboration of a myelin sheath, and the recognition and ensheathment of axons. This review examines the regulatory mechanisms for each of these steps and compares and contrasts the role of the axon in initiating myelination in the central and peripheral nervous system. C1 NINCDS, LAB DEV NEUROGENET, NIH, BETHESDA, MD 20892 USA. RP Colello, RJ (reprint author), VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT ANAT, RICHMOND, VA 23298 USA. NR 143 TC 29 Z9 31 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD AUG PY 1997 VL 15 IS 1 BP 83 EP 100 DI 10.1007/BF02740617 PG 18 WC Neurosciences SC Neurosciences & Neurology GA YF160 UT WOS:A1997YF16000006 PM 9396006 ER PT J AU Conwit, RA Tracy, B Jamison, C McHugh, M Stashuk, D Brown, WF Metter, EJ AF Conwit, RA Tracy, B Jamison, C McHugh, M Stashuk, D Brown, WF Metter, EJ TI Decomposition-enhanced spike-triggered averaging: Contraction level effects SO MUSCLE & NERVE LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the AAEM CY SEP, 1995 CL MONTREAL, CANADA SP AAEM DE spike-triggered averaging; motor unit number estimate; surface-detected motor unit action potential amplitude; contraction level effects; resistance training effects ID THENAR MOTOR UNITS; ISOMETRIC CONTRACTIONS; BICEPS-BRACHIALIS; ESTIMATING NUMBER; RELATIVE SIZES; HUMAN MUSCLES; OLDER ADULTS; RECRUITMENT; COMPUTER AB Decomposition-enhanced spike-triggered averaging (DE-STA) was applied to the vastus medialis muscle to examine size distributions of surface-detected motor unit action potentials (S-MUAPs) at Various force levels, Using DE-STA, 15-20 S-MUAPs were identified during 5%, 10%, 20%, and 30% of maximum voluntary contraction. Average S-MUAPs showed increase in peak to peak (and negative peak) amplitude with force (in mu V): 5% = 37.9 +/- 6.1 (16.6 +/- 2.5), 10% = 44.0 +/- 4.0 (20.4 +/- 1.8), 20% = 80.7 +/- 9.3 (41.3 +/- 4.5), and 30% = 102.5 +/- 10.3 (53.6 +/- 5.0), Test-retest variability of peak to peak (and negative peak amplitude) between repeated trials was 0.10 (0.14), 0.14 (0.14), 0.17 (0.15), and 0.21 (0.20) at 5%, 10%, 20%, and 30% respectively. A relationship was found between the S-MUAP amplitude and force (r(2) = 0.78, df = 90, F = 160, P < 0.001). Increase in average S-MUAP amplitude with force suggests that STA performed only al low levels of contraction may result in a biased sampling and small average S-MUAP amplitudes. (C) 1997 John Wiley & Sons, Inc. C1 UNIV MARYLAND,DEPT KINESIOL,COLLEGE PK,MD 20742. UNIV WATERLOO,DEPT SYST DESIGN ENGN,WATERLOO,ON N2L 3G1,CANADA. TUFTS UNIV NEW ENGLAND MED CTR,NEUROMUSCULAR DIV,BOSTON,MA 02111. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP Conwit, RA (reprint author), JOHNS HOPKINS BAYVIEW MED CTR,DEPT NEUROL,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 33 TC 19 Z9 19 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD AUG PY 1997 VL 20 IS 8 BP 976 EP 982 DI 10.1002/(SICI)1097-4598(199708)20:8<976::AID-MUS7>3.0.CO;2-3 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XL351 UT WOS:A1997XL35100007 PM 9236788 ER PT J AU Koonin, EV Abagyan, RA AF Koonin, EV Abagyan, RA TI TSG101 may be the prototype of a class of dominant negative ubiquitin regulators SO NATURE GENETICS LA English DT Letter ID SACCHAROMYCES-CEREVISIAE; PROTEIN; PATHWAY; CYCLIN C1 NYU,COURANT INST MATH,NEW YORK,NY 10016. NYU,SKIRBALL INST BIOMOL MED,NEW YORK,NY 10016. RP Koonin, EV (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 25 TC 93 Z9 96 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1997 VL 16 IS 4 BP 330 EP 331 DI 10.1038/ng0897-330 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XM909 UT WOS:A1997XM90900009 PM 9241264 ER PT J AU Heppner, C Kester, MB Agarwal, SK Debelenko, LV EmmertBuck, MR Guru, SC Manickam, P Olufemi, SE Skarulis, MC Doppman, JL Alexander, RH Kim, YS Saggar, SK Lubensky, IA Zhuang, ZP Liotta, LA Chandrasekharappa, SC Collins, FS Spiegel, AM Burns, AL Marx, SJ AF Heppner, C Kester, MB Agarwal, SK Debelenko, LV EmmertBuck, MR Guru, SC Manickam, P Olufemi, SE Skarulis, MC Doppman, JL Alexander, RH Kim, YS Saggar, SK Lubensky, IA Zhuang, ZP Liotta, LA Chandrasekharappa, SC Collins, FS Spiegel, AM Burns, AL Marx, SJ TI Somatic mutation of the MEN1 gene in parathyroid tumours SO NATURE GENETICS LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; SUPPRESSOR GENE; TUMORS; CHROMOSOME-11; CARCINOMA; RETINOBLASTOMA; METHYLATION AB Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1), In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2), In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal(3,4), suggesting that one important step in tumour development is a mutation in a progenitor cell, Approximately 30% of sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene(4-8). This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene(9). We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present, Among 33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome. C1 NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NHGRI,LAB GENE TRANSFER,NIH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 35 TC 306 Z9 309 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1997 VL 16 IS 4 BP 375 EP 378 DI 10.1038/ng0897-375 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA XM909 UT WOS:A1997XM90900021 PM 9241276 ER PT J AU Jonas, WB AF Jonas, WB TI Researching alternative medicine SO NATURE MEDICINE LA English DT Editorial Material ID COMPLEMENTARY MEDICINE; RHEUMATOID-ARTHRITIS; METAANALYSIS; TRIAL RP Jonas, WB (reprint author), NIH,OFF ALTERNAT MED,9000 ROCKVILLE PIKE,BLDG 31,ROOM 5B35,MSC 2182,BETHESDA,MD 20892, USA. NR 35 TC 25 Z9 25 U1 1 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 1997 VL 3 IS 8 BP 824 EP 827 DI 10.1038/nm0897-824 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XP014 UT WOS:A1997XP01400015 PM 9256264 ER PT J AU Carbone, M Rizzo, P Grimley, PM Procopio, A Mew, DJY Shridhar, V DeBartolomeis, A Esposito, V Giuliano, MT Steinberg, SM Levine, AS Giordano, A Pass, HI AF Carbone, M Rizzo, P Grimley, PM Procopio, A Mew, DJY Shridhar, V DeBartolomeis, A Esposito, V Giuliano, MT Steinberg, SM Levine, AS Giordano, A Pass, HI TI Simian virus-40 large-T antigen binds p53 in human mesotheliomas SO NATURE MEDICINE LA English DT Article ID LUNG-CARCINOMA; RAS MUTATIONS; MONKEY CELLS; ASBESTOS; GENE; DNA; TRANSFORMATION; INDUCTION; LINES AB We found that simian virus 40 (SV40) induces mesotheliomas in hamsters(1) and that 60% of human mesotheliomas contain and express SV40 sequences', results now confirmed by others [ref. 3-5, and presentations by D. Griffiths & R. Weiss, F. Galateau-SallE, and H.I.P. at ''Simian virus 40: A possible human polyoma virus,'' NIH workshop, 27-28 January 1997, Bethesda, MD (transcript available through SAG Corp., Washington, DC 20008)]. Mesothelioma(6-8), an aggressive malignancy resistant to therapy, originates from the serosal lining of the pleural, pericardial and peritoneal cavities. The incidence of mesothelioma continues to increase worldwide because of exposure to crocidolite asbestos. However, at least 20% of mesotheliomas in the United States are not associated with asbestos exposure, and only a minority of people exposed to high concentrations of asbestos develop mesothelioma(6-8). Thus, other carcinogens may induce mesothelioma in individuals not exposed to asbestos, and/or may render particular individuals more susceptible to the carcinogenic effect of asbestos. We investigated whether the expression of the 5V40 large T-antigen (Tag) interferes with the normal expression of the tumor suppressor gene p53 in human mesotheliomas. We found that SV40 Tag retains its ability to bind and to inactivate p53, a cellular protein that when normally expressed plays an important role in suppressing tumor growth and in inducing sensitivity to therapy. Our findings do not establish a cause-and-effect relation, but indicate that the possibility that SV40 contributes to the development of human mesotheliomas should be carefully investigated. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20889. UNIV CHIETI,LAB FISIOPATOL MOL,I-66013 CHIETI,ITALY. KARMANOS CANC INST,AERODIGEST PROGRAM,DETROIT,MI 48201. NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL ANAT & CELL BIOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,SBARRO INST CANC RES,PHILADELPHIA,PA 19107. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,BETHESDA,MD 20892. RP Carbone, M (reprint author), LOYOLA UNIV,DEPT PATHOL,CANC IMMUNOL PROGRAM,CARDINAL BERNARDIN CANC CTR,ROOM 205,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. RI Giordano, Antonio/F-1927-2010; OI Giordano, Antonio/0000-0002-5959-016X; de Bartolomeis, Andrea/0000-0002-3188-5652 FU NCI NIH HHS [CA 60999-01A1, CA 77220-01A1]; NINDS NIH HHS [NS 36466-01] NR 42 TC 212 Z9 213 U1 0 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 1997 VL 3 IS 8 BP 908 EP 912 DI 10.1038/nm0897-908 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XP014 UT WOS:A1997XP01400035 PM 9256284 ER PT J AU Huth, JR Bewley, CA Nissen, MS Evans, JNS Reeves, R Gronenborn, AM Clore, GM AF Huth, JR Bewley, CA Nissen, MS Evans, JNS Reeves, R Gronenborn, AM Clore, GM TI The solution structure of an HMG-I(Y)-DNA complex defines a new architectural minor groove binding motif SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID PROTEIN-STRUCTURE DETERMINATION; DNA-BINDING; CRYSTAL-STRUCTURE; DIRECT REFINEMENT; PEPTIDE MOTIF; HMG-I/Y; NMR; DOMAIN; GENE; SPECTROSCOPY AB The solution structure of a complex between a truncated form of HMG-I(Y), consisting of the second and third DNA binding domains (residues 51-90), and a DNA dodecamer containing the PRDII site of the interferon-beta promoter has been solved by multidimensional nuclear magnetic resonance spectroscopy. The stoichiometry of the complex is one molecule of HMC-I(Y) to two molecules of DNA. The structure reveals a new architectural minor groove binding motif which stabilizes B-DNA, thereby facilitating the binding of other transcription factors in the opposing major groove. The interactions involve a central Arg-Gly-Arg motif together with two other modules that participate in extensive hydrophobic and polar contacts. The absence of one of these modules in the third DNA binding domain accounts for its similar to 100 fold reduced affinity relative to the second one. C1 NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. WASHINGTON STATE UNIV,DEPT BIOCHEM & BIOPHYS,PULLMAN,WA 99164. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 46 TC 236 Z9 242 U1 1 U2 14 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD AUG PY 1997 VL 4 IS 8 BP 657 EP 665 DI 10.1038/nsb0897-657 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA XP316 UT WOS:A1997XP31600017 PM 9253416 ER PT J AU Kvetnansky, R Pacak, K Tokarev, D Jelokova, J Jezova, D Rusnak, M AF Kvetnansky, R Pacak, K Tokarev, D Jelokova, J Jezova, D Rusnak, M TI Chronic blockade of nitric oxide synthesis elevates plasma levels of catecholamines and their metabolites at rest and during stress in rats SO NEUROCHEMICAL RESEARCH LA English DT Article DE norepinephrine; epinephrine; dopamine; dihydroxyphenylglycol (DHPG); dihydroxyphenylacetic acid (DOPAC); immobilization stress; nitric oxide synthase inhibition; nitro-L-arginine methylesther (L-NAME) ID INHIBITS NOREPINEPHRINE RELEASE; SYMPATHETIC-NERVE STIMULATION; PIG PULMONARY-ARTERY; IMMOBILIZATION STRESS; NEUROEFFECTOR TRANSMISSION; MESENTERIC VASCULATURE; CHROMAFFIN CELLS; HYPERTENSIVE RAT; L-ARGININE; NORADRENALINE AB Formation of nitric oxide, an endothelium-derived relaxing factor, can be inhibited by administration of N-nitro-L-arginine methylesther (L-NAME). In the present study, the activity of the sympathoadrenal system in rats with blood pressure (BP) elevation induced by L-NAME was investigated. L-NAME was administered in a dose of 50 mg/kg, i.p. every 12 h for 4 days. Blood samples were collected via chronically inserted arterial catheters in conscious, freely moving rats at rest and during immobilization stress. Plasma epinephrine (EPI), norepinephrine (NE), and dopamine (DA), as well as catecholamine metabolites dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) were measured by HPLC method. In L-NAME treated animals, which showed a significant increase in BP, plasma EPI levels were markedly elevated both before and during stress. Plasma NE levels were not significantly increased, however, DHPG levels, which indicate NE turnover and reuptake, were highly elevated. Plasma DA levels were not changed after L-NAME administration but DA metabolite DOPAC showed a significant elevation both under basal conditions and during stress. Thus, the present results indicate that the prolonged blockade of nitric oxide synthesis that causes arterial hypertension is associated with an activation of the sympathoadrenal system. C1 WASHINGTON HOSP CTR,DEPT MED,WASHINGTON,DC 20010. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. RP Kvetnansky, R (reprint author), SLOVAK ACAD SCI,INST EXPT ENDOCRINOL,VLARSKA 3,BRATISLAVA 83306,SLOVAKIA. NR 39 TC 19 Z9 21 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD AUG PY 1997 VL 22 IS 8 BP 995 EP 1001 DI 10.1023/A:1022426910111 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA XK784 UT WOS:A1997XK78400011 PM 9239755 ER PT J AU Ye, FQ Smith, AM Yang, YH Duyn, J Mattay, VS Ruttimann, UE Frank, JA Weinberger, DR McLaughlin, AC AF Ye, FQ Smith, AM Yang, YH Duyn, J Mattay, VS Ruttimann, UE Frank, JA Weinberger, DR McLaughlin, AC TI Quantitation of regional cerebral blood flow increases during motor activation: A steady-state arterial spin tagging study SO NEUROIMAGE LA English DT Article ID HUMAN BRAIN; SENSORY STIMULATION; PERFUSION; MOVEMENTS; INVERSION; IMAGES; WATER; EPI; PET AB Steady-state arterial. spin tagging MRI approaches were used to quantitate regional cerebral blood flow increases during finger tapping tasks in seven normal subjects. Statistically significant increases in cerebral blood flow were observed ill the contralateral primary sensorimotor cortex in all seven subjects and in the supplementary motor area in five subjects. The intrinsic spatial resolution of the cerebral blood flow images was similar to 4 mna. If no spatial filtering was applied, the average increase in cerebral blood flow in the activated primary sensorimotor cortex was 60 +/- 10 cc/100 g/min (91 +/- 32%). If the images were filtered to a spatial resolution of 15 mm, the average increase in cerebral blood flow in the activated primary sensorimotor cortex was 23 +/- 7 cc/100 g/min (42 +/- 15%), in agreement with previously reported Xe-133 slid PET results. (C) 1997 Academic Press. C1 NIH,OIR,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. NIAAA,CLIN STUDIES LAB,NIH,BETHESDA,MD. RP Ye, FQ (reprint author), NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010 NR 29 TC 47 Z9 47 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 1997 VL 6 IS 2 BP 104 EP 112 DI 10.1006/nimg.1997.0282 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA XW955 UT WOS:A1997XW95500004 PM 9299384 ER PT J AU Pette, M Pette, DF Muraro, PA Farnon, E Martin, R McFarland, HF AF Pette, M Pette, DF Muraro, PA Farnon, E Martin, R McFarland, HF TI Interferon-beta interferes with the proliferation but not with the cytokine secretion of myelin basic protein-specific, T-helper type 1 lymphocytes SO NEUROLOGY LA English DT Article ID REMITTING MULTIPLE-SCLEROSIS; GAMMA-PRODUCTION; CELL ACTIVATION; INDIVIDUALS AB Interferon-beta (IFN-beta) has beneficial effects on the frequency and severity of relapses, as well as on disease progression in patients suffering from relapsing-remitting MS. Its mode of action, however, is not completely understood. Previous studies on T-lymphocyte bulk cultures and T-lymphocyte lines with specificity for different antigens suggested that the drug might partially act via suppression of T-cell proliferation and secretion of proinflammatory cytokines like interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha). In this study we investigated the effects of human recombinant IFN-beta(1b) on proliferation, interleukin 2 (IL-2) receptor (IL-2R) alpha-chain upregulation, and cytokine and chemokine secretion of myelin basic protein-reactive, MS patient-derived T-cell clones secreting T-helper type 1 (Th1) cytokines. IFN-beta partially suppressed both antigen-and IL-2-driven proliferation of these cells without affecting the expression of either IL-2 or IL-2R alpha-chain. There was no inhibitory effect on the secretion of IFN-gamma, TNF-alpha, and macrophage inflammatory protein (MIP)-1 alpha, but release was rather slightly enhanced. In conclusion, while IFN-beta does reduce proliferation of Th1-like, MBP-specific T cells in vitro, the drug does not result in overall dysfunction of these cells. Therefore, the effect of IFN-beta on MS may not depend on a primary inhibition of potentially encephalitogenic T lymphocytes. RP Pette, M (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH,BLDG 10,RM 5B16,10 CTR DR MSC 1400,BETHESDA,MD 20892, USA. NR 26 TC 40 Z9 40 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 AUG PY 1997 VL 49 IS 2 BP 385 EP 392 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA XR937 UT WOS:A1997XR93700012 PM 9270566 ER PT J AU Samii, A Wassermann, EM Hallett, M AF Samii, A Wassermann, EM Hallett, M TI Decreased postexercise facilitation of motor evoked potentials in patients with cerebellar degeneration SO NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; POST-TETANIC POTENTIATION; LONG-TERM POTENTIATION; ELECTRICAL-STIMULATION; SYNAPTIC TRANSMISSION; CORTICAL POTENTIALS; FATIGUE; DEPRESSION; CORTEX; HIPPOCAMPUS AB We studied the effects of exercise an motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects and II medication-free patients with cerebellar degeneration. Subjects performed repealed sets of isometric exercise of the extensor carpi radialis muscle until the muscle fatigued (subject became unable to maintain half maximal force). MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean preexercise MEP amplitude in normal subjects and 132% in cerebellar patients, indicating postexercise MEP facilitation in both groups. However, postexercise MEP facilitation, compared with the mean preexercise MEP amplitude, was not significant in the patients but was significant in the normal subjects. The amplitudes of MEPs recorded within the first few minutes after fatigue were 44% of the mean preexercise MEP amplitudes in both groups. We conclude that in patients with cerebellar degeneration, postexercise MEP facilitation is significantly reduced, whereas postexercise MEP depression after fatigue is similar to that of normal subjects. C1 NINCDS, HUMAN MOTOR CONTROL SECT, MED NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 44 TC 15 Z9 15 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 AUG PY 1997 VL 49 IS 2 BP 538 EP 542 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA XR937 UT WOS:A1997XR93700038 PM 9270592 ER PT J AU McLean, CA Storey, E Gardner, RJM Tannenberg, AEG Cervenakova, L Brown, P AF McLean, CA Storey, E Gardner, RJM Tannenberg, AEG Cervenakova, L Brown, P TI The D178N (cis-129M) ''fatal familial insomnia'' mutation associated with diverse clinicopathologic phenotypes in an Australian kindred SO NEUROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN GENE; CODON-178; FEATURES AB Fatal familial insomnia (FFI) is an inherited prion disease characterized by progressive insomnia and dysautonomia with only modest cognitive impairment early in the disease, associated with atrophy and gliosis in the medial thalamus, but without: spongiform change. FFI is associated with an aspartic acid to asparagine mutation at codon 178 of the PrP gene (D178N) in conjunction with methionine at the codon 129 polymorphic site on the mutant allele (cis-129M). We report a pedigree with this genotype in which marked clinicopathologic phenotypic heterogeneity occurred including typical Creutzfeldt-Jakob disease, FFI; and what was thought to be an autosomal dominant cerebellar ataxia (ADCA)-like illness, suggesting that the genotype-phenotype correlation is not as tight for this mutation as is frequently supposed. C1 ROYAL MELBOURNE HOSP,DEPT ANAT PATHOL,MELBOURNE,VIC,AUSTRALIA. ROYAL MELBOURNE HOSP,DEPT NEUROL,MELBOURNE,VIC,AUSTRALIA. ROYAL MELBOURNE HOSP,NEUROGENET CLIN,MELBOURNE,VIC,AUSTRALIA. ROYAL CHILDRENS HOSP,MURDOCH INST,VICTORIAN CLIN GENET SERV,PARKVILLE,VIC 3052,AUSTRALIA. MATER MISERICORDIAE HOSP,DEPT PATHOL,BRISBANE,QLD,AUSTRALIA. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. RP McLean, CA (reprint author), UNIV MELBOURNE,DEPT PATHOL,PARKVILLE,VIC 3052,AUSTRALIA. NR 17 TC 46 Z9 46 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1997 VL 49 IS 2 BP 552 EP 558 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA XR937 UT WOS:A1997XR93700041 PM 9270595 ER PT J AU Ryba, NJP Tirindelli, R AF Ryba, NJP Tirindelli, R TI A new multigene family of putative pheromone receptors SO NEURON LA English DT Article ID ACCESSORY OLFACTORY-BULB; VOMERONASAL SYSTEM; MOLECULAR-CLONING; G-PROTEINS; DIFFERENTIAL LOCALIZATION; SIGNAL-TRANSDUCTION; ADENYLYL-CYCLASE; GENE-EXPRESSION; BINDING PROTEIN; NEURONS AB The vomeronasal organ (VNO) mediates detection of pheromones related to social and reproductive behavior in most terrestrial vertebrates. We have identified a new multigene family of G protein-linked receptors (V2Rs) that are specifically expressed in the VNO. V2Rs have no significant homology to other putative pheromone receptors (V1Rs) or to olfactory receptors but are related to the Ca2+-sensing receptor and metabotropic glutamate receptors. V2Rs are expressed at high levels in small subpopulations of VNO neurons. V2Rs are primarily expressed in a different layer of VNO neurons from V1Rs, thus both gene families are likely to encode mammalian pheromone receptors. C1 UNIV PARMA,IST FISIOL UMANA,I-43100 PARMA,ITALY. RP Ryba, NJP (reprint author), NIDR,TASTE & SMELL UNIT,ORAL INFECT & IMMUNOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 48 TC 426 Z9 436 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD AUG PY 1997 VL 19 IS 2 BP 371 EP 379 DI 10.1016/S0896-6273(00)80946-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XU146 UT WOS:A1997XU14600015 PM 9292726 ER PT J AU Bushell, CM Martin, A AF Bushell, CM Martin, A TI Automatic semantic priming of nouns and verbs in patients with Alzheimer's disease SO NEUROPSYCHOLOGIA LA English DT Article DE semantic memory; aphasia; category-specific deficits; language ID LEXICAL-DECISION TASK; SENILE DEMENTIA; SPREADING ACTIVATION; NEURAL SYSTEMS; HUMAN BRAIN; MEMORY; KNOWLEDGE; IMPAIRMENT; RETRIEVAL; DEFICITS AB The status of semantic representations of nouns (concrete and abstract) and verbs (motion and non-motion) was investigated in patients with Alzheimer's disease (AD). Nouns and verbs have been argued to activate different neural substrates, given the selective difficulties reported for one or the other grammatical class in patients with focal lesions. Additionally, category-specific deficits have been reported for either abstract or concrete words, often in patients with bilateral neuropathology. We looked for these types of dissociations in patients with AD in a semantic priming experiment using a pronunciation task and a short stimulus onset asynchrony. The normal control subjects demonstrated automatic activation for both concrete nouns and motion verbs. The AD patients, however, demonstrated priming effects for concrete nouns, but not for motion verbs. This dissociation between concrete nouns and motion verbs found for the AD patients is discussed in terms of differences in the nature of semantic representations involving multiple physical and functional attributes in the case of concrete nouns, but only motion attributes in the case of motion verbs. Moreover, the typical distribution of neuropathology associated with AD may put motion verbs at risk, particularly given the neuroanatomical considerations suggested by recent positron emission tomography (PET) studies. C1 NIMH,LAB BRAIN & COGNIT,BETHESDA,MD 20896. RI martin, alex/B-6176-2009 NR 67 TC 20 Z9 21 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD AUG PY 1997 VL 35 IS 8 BP 1059 EP 1067 DI 10.1016/S0028-3932(97)00046-8 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA XM391 UT WOS:A1997XM39100001 PM 9256370 ER PT J AU Altemus, M Redwine, L Leong, YM Yoshikawa, T Yehuda, R DeteraWadleigh, S Murphy, DL AF Altemus, M Redwine, L Leong, YM Yoshikawa, T Yehuda, R DeteraWadleigh, S Murphy, DL TI Reduced sensitivity to glucocorticoid feedback and reduced glucocorticoid receptor mRNA expression in the luteal phase of the menstrual cycle SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material DE glucocorticoid receptor; menstrual cycle; lymphocyte; dexamethasone; cortisol; mRNA ID CORTICOTROPIN-RELEASING HORMONE; DEXAMETHASONE SUPPRESSION TEST; PITUITARY-ADRENAL AXIS; POTENTIAL CLINICAL IMPLICATIONS; POSTTRAUMATIC-STRESS-DISORDER; ESTROGEN-INDUCED ALTERATIONS; II CORTICOSTEROID RECEPTORS; MESSENGER-RIBONUCLEIC-ACID; RAT-BRAIN; FEMALE RAT AB We examined the effects of the menstrual cycle on hypothalamic-pituitary adrenal axis regulation in healthy women with no history of psychiatric illness by measuring plasma cortisol responses to a low-dose (0.25 mg) of dexamethasone (N = 23) and by measuring glucocorticoid receptor (type II) mRNA expression in lymphocytes using Northern blotting (N = 19). Both measures were performed in the early follicular and mid-luteal phases of the menstrual cycle. Dexamethasone suppression of plasma cortisol was greater in the follicular phase of the menstrual cycle compared to the mid-luteal phase (p < .01). In addition, type II glucocorticoid receptor mRNA expression in lymphocytes was 78% higher in the follicular phase compared to the mid-luteal phase (p < .02). These results indicate that glucocorticoid feedback regulation of the hypothalamic-pituitary-adrenal axis is reduced in the midluteal phase of the menstrual cycle. Reduced feedback regulation of central stress response systems may play a role in generation of common premenstrual symptoms of irritability and dysphoria. Published by Elsevier Science Inc. C1 GEORGETOWN UNIV, SCH MED, DEPT PHARMACOL, WASHINGTON, DC 20057 USA. NIMH, CLIN NEUROGENET BRANCH, DIV INTRAMURAL RES PROGRAMS, BETHESDA, MD USA. MT SINAI SCH MED, DEPT PSYCHIAT, NEW YORK, NY USA. RP Altemus, M (reprint author), CORNELL UNIV, COLL MED, DEPT PSYCHIAT, BOX 244, 1300 YORK AVE, NEW YORK, NY 10021 USA. OI Redwine, Laura/0000-0001-7633-2034 NR 106 TC 57 Z9 57 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1997 VL 17 IS 2 BP 100 EP 109 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XM913 UT WOS:A1997XM91300006 PM 9252985 ER PT J AU Katz, MM Bowden, C Stokes, P Casper, R Frazer, A Koslow, SH Kocsis, J Secunda, S Swann, A Berman, N AF Katz, MM Bowden, C Stokes, P Casper, R Frazer, A Koslow, SH Kocsis, J Secunda, S Swann, A Berman, N TI Can the effects of antidepressants be observed in the first two weeks of treatment? SO NEUROPSYCHOPHARMACOLOGY LA English DT Letter ID MAJOR DEPRESSIVE DISORDER; AMITRIPTYLINE; PLACEBO; IMIPRAMINE; PATTERN; ONSET RP Katz, MM (reprint author), NIMH,CRB COLLABORAT PROGRAM PSYCHOBIOL DEPRESS,BETHESDA,MD 20892, USA. NR 17 TC 11 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1997 VL 17 IS 2 BP 110 EP 112 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XM913 UT WOS:A1997XM91300007 PM 9252986 ER PT J AU Park, CS Lee, HS Lee, HY Krishna, G AF Park, CS Lee, HS Lee, HY Krishna, G TI An unprocessed pseudogene of inducible nitric oxide synthase gene in human SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE inducible nitric oxide synthase; unprocessed pseudogene; FISH; human ID MOLECULAR-CLONING; CHROMOSOMAL LOCALIZATION; STRUCTURAL DIVERSITY; BRAIN; EXPRESSION; MESSENGER; ISOFORM; REGION; NOS2 AB Inducible nitric oxide synthase (iNOS or NOSII) is one of three distinct NOS isoforms in human, The NOSII isoform is expressed in a variety of cells and tissues in response to endotoxins and cytokines, The human genome contains at least two loci for the NOSII gene, one of which (NOSII-1) has previously been assigned to proximal region of the long arm (cen-q11.2 or q11.2-q12) or to pericentric (p11-q11) regions of chromosome 17. The present study, carried out using fluorescence in situ hybridization (FISH) method, shows that a pseudogene gene (NOSII-2) is mapped to chromosome 17q11.2 site, The NOSII-2 sequence contains the exon and intron sequences present in NOSII-1 but with several mutations such as single base substitutions, additions, and deletions. Additionally, the NOSII-2 sequence also contains an incomplete reductase domain which corresponds only to the cofactor binding sites without the oxygenase domain that carry heme and substrate binding sites. NOSII-2, therefore, appears to be an unprocessed pseudogene, which cannot be translated to a functional enzyme because of its incomplete sequences and mutations. (C) 1997 Academic Press. C1 NHLBI, Lab Mol Immunol, Sect Chem Pharmacol, Bethesda, MD 20892 USA. NCI, Sect Expt Oncol, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Inha Univ, Dept Biol, Nam Gu, Inchon 402751, South Korea. RP Park, CS (reprint author), Inha Univ, Coll Med, Dept Pharmacol & Toxicol, Nam Gu, 253 Yonghyun Dong, Inchon 402751, South Korea. EM parkshin@dragon.inha.ac.kr NR 27 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD AUG PY 1997 VL 1 IS 4 BP 294 EP 300 DI 10.1006/niox.1997.0138 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZG183 UT WOS:000072975500003 PM 9441901 ER PT J AU De Luca, LM Ross, SA AF De Luca, LM Ross, SA TI Retinoic acid as a therapy for emphysema? SO NUTRITION REVIEWS LA English DT Review ID DIFFERENTIATION; PATTERN; ALTERS; LUNG AB In concert with its action as a morphogen during embryonal development, retinoic acid appears to be able to regenerate lung alveoli in an experimental model of elastase-induced emphysema in rats, thereby inhibiting manifestation of the disease. The application to humans is now an interesting possibility. C1 NCI, DIFFERENTIAT CONTROL SECT, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD AUG PY 1997 VL 55 IS 8 BP 307 EP 308 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA XU971 UT WOS:A1997XU97100005 PM 9287482 ER PT J AU Schmidt, LA Greenberg, BD Holzman, GB Schulkin, J AF Schmidt, LA Greenberg, BD Holzman, GB Schulkin, J TI Treatment of depression by obstetrician-gynecologists: A survey study SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PRIMARY-CARE; PREVALENCE AB Objective: We performed an exploratory survey of depression diagnosis, treatment, and patient referral patterns by Fellows of ACOG. We also examined obstetrician-gynecologists' professional training in the management of clinical depression. Methods: We sent a questionnaire to a total of 1370 ACOG Fellows. Sixty percent of the surveys were returned. Results: As a group, obstetrician-gynecologists reported diagnosing an average of four new cases of depression per month. Within the overall sample, the number of new diagnoses of depression made each month was significantly greater for those defining themselves as primary care physicians than for those defining themselves as specialists. When treating depression pharmacologically, obstetrician-gynecologists reported that they overwhelmingly (74% of the time) chose selective serotonin reuptake inhibitor antidepressants. Ninety-five percent of obstetrician-gynecologists reported that they referred severely depressed patients to a mental health professional. A majority of respondents neither received residency training (80%) nor completed a continuing medical education course (60%) on the treatment of clinical depression in women. Conclusion: Obstetrician-gynecologists who describe themselves as primary care physicians make significantly more diagnoses of depression than those considering themselves specialists. Studies further to assess obstetrician-gynecologists' management of depression and better to define needs for professional education are warranted. (C) 1997 by The American College of Obstetricians and Gynecologists. C1 AMER COLL OBSTETRICIANS & GYNECOLOGISTS,RES DEPT,WASHINGTON,DC 20024. UNIV MARYLAND,INST CHILD STUDY,COLLEGE PK,MD 20742. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. FU PHS HHS [MCJ 117016] NR 11 TC 49 Z9 50 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD AUG PY 1997 VL 90 IS 2 BP 296 EP 300 DI 10.1016/S0029-7844(97)00255-X PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XM912 UT WOS:A1997XM91200028 PM 9241311 ER PT J AU Green, FHY Harley, R Vallyathan, V Althouse, R Fick, G Dement, J Mitha, R Pooley, F AF Green, FHY Harley, R Vallyathan, V Althouse, R Fick, G Dement, J Mitha, R Pooley, F TI Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos workers SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE asbestos; chrysotile; tremolite; lung fibre burden ID FIBER CONTENT; LUNG-TISSUE; QUANTITATIVE ASSESSMENT; RESPIRATORY CANCER; TEXTILE WORKERS; DUST EXPOSURE; DISEASE; MORTALITY; MINERS; MILLERS AB Objectives-The relation between lifetime cumulative exposure to asbestos, pathological grade of pulmonary fibrosis, and lung burden of asbestos at death, was explored in a necropsy population of former workers in a chrysotile asbestos textile plant in South Carolina. Methods-Estimates of cumulative, mean, and peak exposures to asbestos were available for 54 workers. Necropsy records and lung tissue samples were obtained from hospital files. Matched control cases were selected from consecutive necropsies performed at the same hospitals. The extent and severity of pulmonary fibrosis was graded on tissue sections. Mineral fibres in lung tissue were characterised by transmission electron microscopy combined with x ray spectroscopy. Results-A significant positive correlation (r = 0.67, P< 0.0001) was found between lifetime cumulative exposure to asbestos and total lung burden of asbestos fibres. This relation was also found for the individual types of asbestos associated with the exposure: chrysotile and tremolite. Pulmonary fibrosis was correlated with both cumulative exposure to asbestos (r = 0.60, P< 0.01) and the concentration of asbestos fibres in the lung (r = 0.62, P< 0.0001). The concentration of tremolite fibres in the lung provided a better estimate of lung fibrosis than did the concentration of chrysotile. Asbestosis was usually present in asbestos textile workers with more than 20 fibre-years cumulative exposure. The lengths and aspect ratios of chrysotile asbestos, but not amphibole asbestos, were greater in the lungs of asbestos fibre workers than in the control population. Textile workers with lung cancer had significantly greater cumulative exposures and fibrosis scores than workers without lung cancer. Conclusions-Both cumulative exposure to asbestos and lung fibre burden are strongly correlated with severity of asbestosis. The data also support the hypothesis that the high prevalence of asbestosis and lung cancer in this population resulted from exposure to long fibres of chrysotile asbestos in the workplace. C1 UNIV CALGARY,DEPT COMMUNITY HLTH,CALGARY,AB T2N 4N1,CANADA. UNIV S CAROLINA,CHARLESTON,SC. NIOSH,DIV RESP DIS STUDIES,MORGANTOWN,WV 26505. NIEHS,RES TRIANGLE PK,NC 27709. UNIV WALES COLL CARDIFF,CARDIFF,S GLAM,WALES. RP Green, FHY (reprint author), UNIV CALGARY,DEPT PATHOL,3330 HOSPITAL DR NW,CALGARY,AB T2N 4N1,CANADA. NR 45 TC 37 Z9 37 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD AUG PY 1997 VL 54 IS 8 BP 549 EP 559 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XQ935 UT WOS:A1997XQ93500004 PM 9326158 ER PT J AU Magno, BV Datiles, MB Lasa, MSM Fajardo, MRQ Caruso, RC KaiserKupfer, MI AF Magno, BV Datiles, MB Lasa, MSM Fajardo, MRQ Caruso, RC KaiserKupfer, MI TI Evaluation of visual function following Neodymium:YAG laser posterior capsulotomy SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 14-19, 1995 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol ID CONTRAST SENSITIVITY; GLARE SENSITIVITY; DISABILITY GLARE; EARLY CATARACTS; ACUITY; ND; OPACIFICATION; VISION AB Purpose: Improvement in visual acuity is the primary endpoint for successful neodymium:YAG (Nd:YAG) laser posterior capsulotomy for posterior capsule opacification. There is limited information on related parameters of visual function that may also improve after laser treatment. The authors evaluate changes in contrast sensitivity and glare disability, aside from visual acuity, following Nd:YAG laser posterior capsulotomy, Methods: Measurements of visual acuity, contrast sensitivity (using the Pelli-Robson chart), and glare disability (using the Brightness Acuity Tester [Mentor O & O, Inc., Norwell, MA]) were obtained from 24 consecutive patients before and after Nd:YAG laser posterior capsulotomy, Glare testing was done with both the Pelli-Robson and Early Treatment Diabetic Retinopathy Study (ETDRS) charts, The degree of glare disability was indicated by the difference between visual function with glare (at medium and high settings) and without glare. Prelaser measurements were taken within 2 weeks prior to treatment, and postlaser measurements were obtained within 3 months after treatment. Only one eye per patient was evaluated, Results: Mean differences between prelaser and postlaser measurements were significantly different from zero: (1) Contrast sensitivity, mean difference = 0.24 log units (P < 0.0001); (2) High glare disability using Pelli-Robson chart, mean difference = 0.15 log units (P = 0.004); (3) Visual acuity using ETDRS chart, mean difference = 11 letters (P < 0.0001); 4) High glare disability using ETDRS chart, mean difference = 7 letters (P = 0.005). Conclusions: Using the above methods for visual function testing, Nd:YAG laser capsulotomy is shown to significantly improve visual acuity, contrast sensitivity, and glare disability measurements as compared with prelaser values, The ophthalmologist may find it helpful to document the last two measurements prior to Nd:YAG laser capsulotomy, especially in patients who have good visual acuity but complain of glare sensitivity. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,NIH,BETHESDA,MD 20892. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 32 TC 35 Z9 39 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1997 VL 104 IS 8 BP 1287 EP 1293 PG 7 WC Ophthalmology SC Ophthalmology GA XP841 UT WOS:A1997XP84100022 PM 9261315 ER PT J AU Berthold, CW Dionne, RA Corey, SE AF Berthold, CW Dionne, RA Corey, SE TI Comparison of sublingually and orally administered triazolam for premedication before oral surgery SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID ABSORPTION; DIAZEPAM; PLACEBO; FOOD AB Objectives. This study evaluated sublingual administration of triazolam for preoperative sedation in dental outpatients. Study design. A double-blind, placebo-controlled study compared 0.25 mg sublingual triazolam, 0.25 mg oral triazolam, and placebo administered 1 hour before oral surgery. Results. Sublingual triazolam resulted in significantly less anxiety and pain at 15 minutes intraoperatively than both oral triazolam and placebo (p < 0.05). Patients' global evaluation of the efficacy of sedation ranked sublingual triazolam as significantly more efficacious than placebo (p < 0.05) with oral triazolam intermediate between the two. No difference was demonstrated in the rate of. recovery or incidence of side effects between the two drug groups. Plasma triazolam levels were higher after sublingual administration during and after the surgical procedure. Conclusions. These results indicate that sublingual triazolam results in greater anxiolytic activity and less pain perception than oral administration as a result of greater plasma drug levels and may be useful as an alternative for nonparenteral outpatient sedation. C1 NIDR,NIH,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH PHARM,PITTSBURGH,PA. NR 23 TC 17 Z9 17 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD AUG PY 1997 VL 84 IS 2 BP 119 EP 124 DI 10.1016/S1079-2104(97)90055-X PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA XR145 UT WOS:A1997XR14500007 PM 9269010 ER PT J AU Caudle, RM AF Caudle, RM TI Comments on Andersen et al, Pain, 67 (1996) 369 SO PAIN LA English DT Letter ID NMDA RECEPTOR; POTENTIATION; DEXTRORPHAN; ANTAGONIST; RAT RP Caudle, RM (reprint author), NIDR,NIH,BLDG 49,ROOM 1A-11,49 CONVENT DR,MSC 4410,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD AUG PY 1997 VL 72 IS 1-2 BP 283 EP 284 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA XM773 UT WOS:A1997XM77300035 PM 9272815 ER PT J AU Shad, A Magrath, I AF Shad, A Magrath, I TI Non-Hodgkin's lymphoma SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID LARGE-CELL LYMPHOMA; PEDIATRIC-ONCOLOGY-GROUP; TUMOR-LYSIS-SYNDROME; ACUTE LYMPHOBLASTIC-LEUKEMIA; AFRICAN BURKITTS-LYMPHOMA; FRANKFURT-MUNSTER GROUP; BARR-VIRUS ASSOCIATION; HIGH-DOSE METHOTREXATE; C-MYC ONCOGENE; T-CELL AB Pediatric lymphomas are the third most common group of malignancies in children and adolescents. Unlike lymphomas in adults, pediatric lymphomas are diffuse, aggressive neoplasms with a propensity for widespread dissemination. Intensification of conventional treatment approaches along with improvements in supportive care have resulted in dramatic improvement in event-free survival rates of close to 90% in patients with B-cell lymphomas and only slightly lower in patients with T-cell lymphomas. Lymphoid neoplasms arise because of genetic changes that result in altered growth and differential patterns of lymphoid cells. The characterization of these molecular abnormalities and an understanding of their consequences has led to new approaches to diagnosis and the detection of minimal residual disease and also provides the basis for the future development of novel treatment approaches targeted specifically to the neoplastic cells. C1 NCI,LYMPHOMA BIOL SECT,PEDIAT BRANCH,BETHESDA,MD 20892. RP Shad, A (reprint author), GEORGETOWN UNIV,MED CTR,DIV PEDIAT HEMATOL ONCOL,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007, USA. NR 147 TC 20 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 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD AUG PY 1997 VL 44 IS 4 BP 863 EP & DI 10.1016/S0031-3955(05)70534-4 PG 30 WC Pediatrics SC Pediatrics GA XT840 UT WOS:A1997XT84000006 PM 9286289 ER PT J AU Kattwinkel, J Brooks, J Keenan, ME Malloy, M Willinger, M AF Kattwinkel, J Brooks, J Keenan, ME Malloy, M Willinger, M TI Does bed sharing affect the risk of SIDS? SO PEDIATRICS LA English DT Editorial Material AB The American Academy of Pediatrics endorses and accepts as its policy the position on bed sharing as articulated below by a panel of experts convened by the National Institute of Child Health and Human Development (NICHD). The Panel attended a conference sponsored by the NICHD entitled ''lnfant Sleep Environment and SIDS Risk'' in Bethesda, MD, on January 9-10, 1997. After hearing presentations from a variety of experts from the United States and several other countries, the Panel prepared the following statement regarding the relationship of bed sharing and SIDS. C1 UNIV VIRGINIA,CHARLOTTESVILLE,VA. BOSTON UNIV,BOSTON,MA 02215. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. WASHINGTON UNIV,ST LOUIS,MO. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. NICHHD,BETHESDA,MD 20892. RP Kattwinkel, J (reprint author), DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,HANOVER,NH 03756, USA. NR 0 TC 40 Z9 41 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 1997 VL 100 IS 2 BP 272 EP 272 PG 1 WC Pediatrics SC Pediatrics GA XP050 UT WOS:A1997XP05000031 ER PT J AU Mackenzie, PI Owens, IS Burchell, B Bock, KW Bairoch, A Belanger, A FournelGigleux, S Green, M Hum, DW Iyanagi, T Lancet, D Louisot, P Magdalou, J Chowdhury, JR Ritter, JK Schachter, H Tephly, TR Tipton, KF Nebert, DW AF Mackenzie, PI Owens, IS Burchell, B Bock, KW Bairoch, A Belanger, A FournelGigleux, S Green, M Hum, DW Iyanagi, T Lancet, D Louisot, P Magdalou, J Chowdhury, JR Ritter, JK Schachter, H Tephly, TR Tipton, KF Nebert, DW TI The UDP glycosyltransferase gene superfamily: Recommended nomenclature update based on evolutionary divergence SO PHARMACOGENETICS LA English DT Review DE glycosylation; glucuronidation; evolution; gene nomenclature; hyperbilirubinemia; human genetics ID CRIGLER-NAJJAR-SYNDROME; SYNDROME TYPE-I; BILIRUBIN URIDINE 5'-DIPHOSPHATE-GLUCURONOSYLTRANSFERASE; DRUG-METABOLIZING-ENZYMES; GILBERTS-SYNDROME; MOLECULAR-CLONING; MISSENSE MUTATION; HUMAN PHENOL; GLUCURONOSYLTRANSFERASE; PATIENT AB This review cc represents an update of the nomenclature system for the UDP glucuronosyltransferase gene superfamily, which is based on divergent evolution. Since the previous review in 1991, sequences of many related UDP glycosyltransferases from lower organisms have appeared in the database, which expand our database considerably. At latest count, in animals, yeast, plants and bacteria there are 110 distinct cDNAs/genes whose protein products all contain a characteristic 'signature sequence' and, thus, are regarded as members of the same superfamily, Comparison of a relatedness tree of proteins leads to the definition of 33 families, It should be emphasized that at least six cloned UDP-GlcNAc N-acetylglucosaminyltransferases are not sufficiently homologous to be included as members of this superfamily and may represent an example of convergent evolution, For naming each gene, it is recommended that the root symbol UGT for human (Ugt for mouse and Drosophila), denoting 'UDP glycosyltransferase,' be followed by an Arabic number representing the family, a letter designating the subfamily, and an Arabic numeral denoting the individual gene within the family or subfamily, e.g. 'human UGT2B4' and 'mouse Ugt2b5'. We recommend the name 'UDP glycosyltransferase' because many of the proteins do not preferentially use UDP glucuronic acid, or their nucleotide sugar preference is unknown. Whereas the gene is italicized, the corresponding cDNA, transcript, protein and enzyme activity should be written with upper-case letters and without italics, e.g. 'human or mouse UGT1A1. 'The UGT1 gene (spanning > 500 kb) contains at least 12 promoters/first exons, which call be spliced and joined with common exons 2 through 5, leading to different N-terminal halves but identical C-terminal halves of the gene products; in this scheme each first exon is regarded as a distinct gene (e.g. UGT1A1, UGT1A2, ... UGT1A12). When an orthologous gene between species cannot be identified with certainty, as occurs in the UGT2B subfamily, sequential naming of the genes is being carried out chronologically as they become characterized, We suggest that the Human Gene Nomenclature Guidelines (http://www.gene.acl.ac.uk/nomenclature/guidelines.html) be used for all species other than the mouse and Drosophila. Thirty published human UGT1A1 mutant alleles responsible for clinical hyperbilirubinemias are listed herein, and given numbers following an asterisk (e.g. UGT1A1*30:) consistent with the Human Gene Nomenclature Guidelines. It is anticipated that this UGT gene nomenclature system will require updating on a regular basis. C1 UNIV CINCINNATI,SCH MED,CTR ENVIRONM GENET,CINCINNATI,OH 45267. UNIV CINCINNATI,SCH MED,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267. FLINDERS UNIV S AUSTRALIA,DEPT CLIN PHARMACOL,BEDFORD PK,SA 5042,AUSTRALIA. NICHHD,SECT GENET DISORDERS DRUG METAB,HUMAN GENET BRANCH,BETHESDA,MD 20892. UNIV DUNDEE,NINEWELLS HOSP & MED SCH,DEPT BIOCHEM MED,DUNDEE DD1 9SY,SCOTLAND. UNIV TUBINGEN,DEPT TOXICOL,TUBINGEN,GERMANY. UNIV GENEVA,CTR MED UNIV GENEVA,DEPT BIOCHIM MED,GENEVA,SWITZERLAND. UNIV LAVAL,CTR HOSP,CTR RECH ENDOCRINOL MOL,ST FOY,PQ G1K 7P4,CANADA. UNIV NANCY 1,URA CNRS 1288,F-54506 VANDOEUVRE NANCY,FRANCE. UNIV IOWA,DEPT PHARMACOL,IOWA CITY,IA 52242. HIMEJI INST TECHNOL,FAC SCI,DEPT LIFE SCI,HIMEJI,HYOGO 67122,JAPAN. WEIZMANN INST SCI,DEPT MEMBRANE RES & BIOPHYS,IL-76100 REHOVOT,ISRAEL. UR MED LYON SUD,BIOCHIM LAB,OULLINS,FRANCE. ALBERT EINSTEIN COLL MED,MARION BESSIN LIVER RES CTR,DEPT MED & MOL GENET,NEW YORK,NY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298. HOSP SICK CHILDREN,RES INST,DEPT BIOCHEM,TORONTO,ON M5G 1X8,CANADA. UNIV DUBLIN TRINITY COLL,DEPT BIOCHEM,DUBLIN 2,IRELAND. OI Bairoch, Amos/0000-0003-2826-6444 FU NIEHS NIH HHS [P30 ES06096] NR 58 TC 757 Z9 798 U1 14 U2 71 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD AUG PY 1997 VL 7 IS 4 BP 255 EP 269 DI 10.1097/00008571-199708000-00001 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA XT988 UT WOS:A1997XT98800001 PM 9295054 ER PT J AU Oriji, GK Keiser, HR AF Oriji, GK Keiser, HR TI Protein kinase C mediates angiotensin II-induced contractions and the release of endothelin and prostacyclin in rat aortic rings SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID VASCULAR SMOOTH-MUSCLE; IMMUNOREACTIVE ENDOTHELIN; INOSITOL PHOSPHOLIPIDS; PLATELET ACTIVATION; CELLS; CALCIUM; INCREASES; PHOSPHORYLATION; PROSTAGLANDINS; LIPOMODULIN AB Angiotensin II (Ang II) stimulation of vascular smooth muscle results in a myriad of intracellular signals that interact to produce the final physiologic response of the cell. We used rat aortic rings to investigate the role of protein kinase C (PKC) in Ang II-induced contractions and in the concomitant release of endothelin (ET) and prostacyclin (PGI(2)). Ang II (10(-9)M) produced a rapid contraction which was sustained for 10 min. When aortic rings were pretreated with graded concentrations of each of the four different inhibitors of PKC, that is, (i) 1-(5-isoquinolinesultonylmethyl) piperazine (H7); (ii) 1-(5-isoquinolinesulfonyl) piperazine(CL); (iii) staurosporine; or (iv) calphostin C, inhibition of Ang II-induced contractions began at 10(-9)M, and was nearly complete at 10(-6)M. Ang II-induced contractions were associated with a 10-fold increase in the release of both ET and PGI(2). Pretreatment with 10(-6)M of any one of the same four PKC inhibitors blocked Ang II-induced release of both ET and PGI(2). Pretreatment with a blocker of the endothelin-A receptor, BQ123 (10(-6)M), inhibited, by approximately 50%, Ang II-induced contractions, and the release of both ET and PGI(2). In aortic rings denuded of endothelium, Ang II-induced contractions, and the release of both ET and PGI(2) were significantly reduced, compared to intact rings. We conclude that PKC mediates Ang II-induced contractions in rat aortic rings and that the secondary release of both ET and PGI(2) during Ang II-induced contractions is mediated, at least in part, by PKC. In addition, approximately half of Ang II-induced contractile force and of PGI(2) release is dependent upon the ET released from endothelial cells. RP Oriji, GK (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH,10 CTR DR,MSC 1754,BETHESDA,MD 20892, USA. NR 42 TC 18 Z9 18 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD AUG PY 1997 VL 57 IS 2 BP 135 EP 141 DI 10.1016/S0952-3278(97)90003-X PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA XN106 UT WOS:A1997XN10600004 PM 9250696 ER PT J AU Kawana, Y Komiya, A Ueda, T Nihei, N Kuramochi, H Suzuki, H Yatani, R Imai, T Dong, JT Imai, T Yoshie, O Barrett, JC Isaacs, JT Shimazaki, J Ito, H Ichikawa, T AF Kawana, Y Komiya, A Ueda, T Nihei, N Kuramochi, H Suzuki, H Yatani, R Imai, T Dong, JT Imai, T Yoshie, O Barrett, JC Isaacs, JT Shimazaki, J Ito, H Ichikawa, T TI Location of KAI1 on the short arm of human chromosome 11 and frequency of allelic loss in advanced human prostate cancer SO PROSTATE LA English DT Article DE loss of heterozygosity; prostate cancer; human chromosome 11; KAI1; metastasis suppressor gene ID TUMOR-SUPPRESSOR GENE; SYNCYTIUM FORMATION; MAMMARY-CANCER; METASTASIS; LOCI; HETEROZYGOSITY; LOCALIZATION; CARCINOMA; PROGRESSION; MARKERS AB BACKGROUND. We recently isolated the KAI1 gene, a metastasis suppressor gene for prostate cancer, from human chromosome region 11p13-cen-containing rat prostate cancer cells. The present study was performed to further locate the region of the KAI1 gene on the short arm of chromosome 11, and to examine whether loss of this region is significant during progression of human prostate cancer. METHODS. The small portion of human chromosome 11 (i.e., 11p13-cen) was reintroduced into highly metastatic rat prostate cancer cells by using microcell-mediated chromosome transfer. Loss of heterozygosity (LOH) at polymorphic microsatellite loci on the human chromosome 11 was examined in human prostate cancer tissues. RESULTS. The minimum region of human chromosome 11 that contained the KAI1 gene was located on the proximal region of 11p11.2 divided by the D11S554 locus. The percentage of LOH or allelic imbalance at the D11S1344 locus, which is located on the same region as the KAI1 locus, in metastasis tissues from autopsy cases who died from metastatic prostate cancer was 70% (7 of 10 informative cases), whereas the percentages in primary tumors from the same cases and from cases with clinically localized prostate cancer were 33% (3 of 9 informative cases) and 8% (1 of 12 informative cases), respectively. CONCLUSIONS. These findings demonstrate a high frequency of LOH or allelic imbalance at the centromeric region of 11p, which contains the KAI1 gene in advanced prostate cancer. (C) 1997 Wiley-Liss, Inc. C1 TEIKYO UNIV, SCH MED, ICHIHARA HOSP, DEPT UROL, ICHIHARA, CHIBA 29901, JAPAN. CHIBA UNIV, SCH MED, DEPT UROL, CHIBA 260, JAPAN. MIE UNIV, FAC MED, DEPT PATHOL, TSU, MIE 514, JAPAN. NATL INST RADIOL SCI, DIV GENET, CHIBA 260, JAPAN. UNIV VIRGINIA, DEPT PATHOL, CHARLOTTESVILLE, VA 22903 USA. SHIONOGI INST MED SCI, SETTSU, OSAKA, JAPAN. NIEHS, MOL CARCINOGENESIS LAB, ENVIRONM CARCINOGENESIS PROGRAM, RES TRIANGLE PK, NC 27709 USA. JOHNS HOPKINS UNIV, SCH MED,JOHNS HOPKINS ONCOL CTR, JAMES BUCHANAN BRADY UROL INST,DEPT UROL, BALTIMORE, MD 21205 USA. NR 27 TC 55 Z9 61 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0270-4137 J9 PROSTATE JI Prostate PD AUG 1 PY 1997 VL 32 IS 3 BP 205 EP 213 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA XN992 UT WOS:A1997XN99200007 PM 9254900 ER PT J AU Wallqvist, A Smythers, GW Covell, DG AF Wallqvist, A Smythers, GW Covell, DG TI Identification of cooperative folding units in a set of native proteins SO PROTEIN SCIENCE LA English DT Article DE autonomous folding units; empirical protein folding potential; structurally conserved amino acids; threading ID PANCREATIC TRYPSIN-INHIBITOR; KNOWLEDGE-BASED POTENTIALS; FRENCH BEAN PLASTOCYANIN; CREVICE-FORMING MUTANTS; AMIDE-PROTON-EXCHANGE; CYTOCHROME-C; STAPHYLOCOCCAL NUCLEASE; HYDROGEN-EXCHANGE; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE AB Cooperative unfolding penalties are calculated by statistically evaluating an ensemble of denatured states derived from native structures. The ensemble of denatured states is determined by dividing the native protein into short contiguous segments and defining all possible combinations of native, i.e., interacting, and non-native, i.e., non-interacting, segments. We use a novel knowledge-based scoring function, derived from a set of non-homologous proteins in the Protein Data Bank, to describe the interactions among residues. This procedure is used for the structural identification of cooperative folding cores for four globular proteins: bovine pancreatic trypsin inhibitor, horse heart cytochrome c, French bean plastocyanin, and staphylococcal nuclease. The theoretical folding units are shown to correspond to regions that exhibit enhanced stability against denaturation as determined from experimental hydrogen exchange protection factors. Using a sequence similarity score for related sequences, we show that, in addition to residues necessary for enzymatic function, those amino acids comprising structurally important folding cores are also preferentially conserved during evolution. This implies that the identified folding cores may be part of an array of fundamental structural folding units. RP Wallqvist, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702, USA. NR 85 TC 19 Z9 19 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 1997 VL 6 IS 8 BP 1627 EP 1642 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XQ361 UT WOS:A1997XQ36100004 PM 9260276 ER PT J AU Wingfield, PT Stahl, SJ Kaufman, J Zlotnick, A Hyde, CC Gronenborn, AM Clore, GM AF Wingfield, PT Stahl, SJ Kaufman, J Zlotnick, A Hyde, CC Gronenborn, AM Clore, GM TI The extracellular domain of immunodeficiency virus gp41 protein: Expression in Escherichia coli, purification, and crystallization SO PROTEIN SCIENCE LA English DT Article DE E-coli protein expression; HIV-1 and SIV gp41 ectodomain; physiochemical analysis; protein crystallization; protein folding and purification; x-ray diffraction ID CIRCULAR-DICHROISM; GLYCOPROTEIN; POLYMERASE; SEQUENCE; FUSION; GENES; AIDS AB The env gene of SN and HIV-1 encodes a single glycoprotein gp160, which is processed to give a noncovalent complex of the soluble glycoprotein gp120 and the transmembrane glycoprotein gp41. The extracellular region (ectodomain), minus the N-terminal fusion peptide, of gp41 from HIV-1 (residues 27-154) and SIV (residues 27-149) have been expressed in Escherichia coli. These insoluble proteins were solubilized and subjected to a simple purification and folding scheme, which results in high yields of soluble protein. Purified proteins have a trimeric subunit composition and high alpha-helical content, consistent with the predicted coil-coil structure. SIV gp41 containing a double cysteine mutation was crystallized. The crystals are suitable for X-ray structure determination and, preliminary analysis, together with additional biochemical evidence, indicates that the gp41 trimer is arranged as a parallel bundle with threefold symmetry. C1 NIAMSD,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Wingfield, PT (reprint author), NIAMSD,PROT EXPRESS LAB,NIH,BLDG 6B,ROOM 1B130,6 CTR DR MSC 2775,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 36 TC 39 Z9 39 U1 0 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 1997 VL 6 IS 8 BP 1653 EP 1660 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XQ361 UT WOS:A1997XQ36100006 PM 9260278 ER PT J AU Neuwald, AF AF Neuwald, AF TI An unexpected structural relationship between integral membrane phosphatases and soluble haloperoxidases SO PROTEIN SCIENCE LA English DT Article DE Aur1p; bromoperoxidase; Dri42; PAP2; PgpB; vanadate ID LYSOPHOSPHATIDIC ACID; COMPLEXES AB The mechanism of a membrane-bound enzyme important in phospholipid signaling, type 2 phosphatidic acid phospha tase, is suggested by sequence motifs shared with a soluble vanadium-dependent chloroperoxidase of known structure, These regions are also conserved in other soluble globular and membrane-associated proteins, including bacterial acid phosphatases, mammalian glucose-6-phosphatases, and the Drosophila developmental protein Wunen. This implies that a similar arrangement of catalytic residues specifies the active sits within both soluble and membrane spanning domains. RP Neuwald, AF (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 30 TC 99 Z9 100 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 1997 VL 6 IS 8 BP 1764 EP 1767 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XQ361 UT WOS:A1997XQ36100017 PM 9260289 ER PT J AU Dasgupta, S Iyer, GH Bryant, SH Lawrence, CE Bell, JA AF Dasgupta, S Iyer, GH Bryant, SH Lawrence, CE Bell, JA TI Extent and nature of contacts between protein molecules in crystal lattices and between subunits of protein oligomers SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE potential of mean force; molecular recognition; protein interfaces; salt bridges; hydrophobic interaction; protein crystallization; contact patches ID MACROMOLECULAR STRUCTURES; SHAPE COMPLEMENTARITY; ACCESSIBLE SURFACE; REPRESENTATIVE SET; DATA-BANK; DOCKING; RECOGNITION; PACKING; INTERFACES; STABILITY AB A survey was compiled of several characteristics of the intersubunit contacts in 58 oligomeric proteins, and of the intermolecular contacts in the lattice for 223 protein crystal structures, The total number of atoms in contact and the secondary structure elements involved are similar in the two types of interfaces, Crystal contact patches are frequently smaller than patches involved in oligomer interfaces, Crystal contacts result from more numerous interactions by polar residues, compared with a tendency toward nonpolar amino acids at oligomer interfaces. Arginine is the only amino acid prominent in both types of interfaces, Potentials of mean Terce far residue-residue contacts at both crystal and oligomer interfaces were derived from comparison of the number of observed residue-residue interactions with the number expected by mass action, They show that hydrophobic interactions at oligomer interfaces favor aromatic amino acids and methionine over aliphatic amino acids; and that crystal contacts form in such a way as to avoid inclusion of hydrophobic interactions, They also suggest that complex salt bridges with certain amino acid compositions might be important in oligomer formation, For a protein that is recalcitrant to crystallization, substitution of lysine residues with arginine or glutamine is a recommended strategy. (C) 1997 Wiley-Liss, Inc. C1 RENSSELAER POLYTECH INST,DEPT CHEM,TROY,NY 12180. RENSSELAER POLYTECH INST,CTR BIOPHYS,TROY,NY 12180. NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894. NEW YORK STATE DEPT HLTH,LAB BIOMETR,WADSWORTH CTR LABS & RES,ALBANY,NY 12237. RI Dasgupta, Swagata/A-3821-2009; OI Dasgupta, Swagata/0000-0003-2074-1247 FU NIGMS NIH HHS [GM50817] NR 56 TC 123 Z9 126 U1 2 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD AUG PY 1997 VL 28 IS 4 BP 494 EP 514 DI 10.1002/(SICI)1097-0134(199708)28:4<494::AID-PROT4>3.0.CO;2-A PG 21 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XP463 UT WOS:A1997XP46300004 PM 9261866 ER PT J AU SamsDodd, F Lipska, BK Weinberger, DR AF SamsDodd, F Lipska, BK Weinberger, DR TI Neonatal lesions of the rat ventral hippocampus result in hyperlocomotion and deficits in social behaviour in adulthood SO PSYCHOPHARMACOLOGY LA English DT Article DE hyperactivity; hippocampus; neonate; negative symptoms; positive symptoms; rat; schizophrenia; social behaviour ID NEGATIVE SYMPTOMS; SCHIZOPHRENIA; CLOZAPINE; AMPHETAMINE; DAMAGE; PHENCYCLIDINE; TRACKING; DRUGS; MODEL; RISK AB The neonatal ibotenic acid lesion of the ventral hippocampus in the rat is an animal model of several aspects of schizophrenia. This lesion produces a number of behavioural abnormalities, such as hyperlocomotion and deficits in prepulse inhibition of startle, that present themselves relatively late in development, i.e. after puberty. Some of these abnormalities, which are thought to model the positive symptoms of schizophrenia, can be normalized by chronic treatment with neuroleptics. In the present study, we examined the effects of the neonatal hippocampal lesion on social behaviour. Social withdrawal and isolation are key components of the negative symptoms of schizophrenia that have not been previously addressed in this model. Rats were lesioned on postnatal day 7 (PD7) and tested for social interaction on PD35 and PD65. They were then treated with clozapine (1.9 and 7.4 mu mol/kg or 0.63 and 2.5 mg/kg) for 21 days and retested. The results show that although, as previously reported, spontaneous hyperlocomotion emerged in the lesioned rats only after puberty (PD65), social interaction deficits and behaviors that may reflect anxiety were present at both PD35 and PD65. Clozapine normalized locomotion, but did not ameliorate putative anxiety or social inter-action deficits in the neonatally lesioned rats. Our results indicate that the neonatal hippocampal lesion in the rat models some aspects of both positive and negative symptoms of schizophrenia. The effects of clozapine appear inconsistent with its putative benefit for negative symptoms. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,IRP,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. RP SamsDodd, F (reprint author), H LUNDBECK & CO AS,PHARMACOL RES,OTTILIAVEJ 9,DK-2500 VALBY,DENMARK. RI Lipska, Barbara/E-4569-2017 NR 32 TC 224 Z9 229 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 1997 VL 132 IS 3 BP 303 EP 310 DI 10.1007/s002130050349 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA XR397 UT WOS:A1997XR39700012 PM 9292631 ER PT J AU Littlefield, LG Travis, LB Sayer, AM Voelz, GL Jensen, RH Boice, JD AF Littlefield, LG Travis, LB Sayer, AM Voelz, GL Jensen, RH Boice, JD TI Cumulative genetic damage in hematopoietic stem cells in a patient with a 40-year exposure to alpha particles emitted by thorium dioxide SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; GLYCOPHORIN-A LOCUS; CHROMOSOME-ABERRATIONS; X-IRRADIATION; LYMPHOCYTES; RADIATION; THOROTRAST; FREQUENCY; MUTATIONS; HUMANS AB Thorotrast, a colloidal suspension of the long-lived radionuclide, thorium-232, was widely used as a radiographic contrast medium far several decades. Due to the poor excretion of the sol, however, Thorotrast would deposit in the liver, bone marrow and other tissue, and patients would receive alpha-particle irradiation for life. To gauge the cumulative genetic damage to hematopoietic stem cells due to chronic exposure to alpha particles, we conducted a multi-end-point evaluation in a 72-year-old man who had been administered a 32-ml bolus of Thorotrast during cerebral angiography performed over 40 years ago in 1950. Peripheral T lymphocytes were cultured to quantify the frequencies and cellular distributions of asymmetrical and symmetrical types of chromosome aberrations in first-division metaphases and micronuclei in cytokinesis-arrested interphase II cells. Aberrations were scored using classical chromosome group analysis methods and chromosome painting techniques. Assays of glycophorin-A (GPA) mutations in red blood cells were also performed to obtain a relative measurement of damage sustained by the erythroid stem cell population. Results revealed that approximately 30% of the lymphocytes in this patient contained one or more chromosome aberrations, the majority of which were of the ''stable'' type. About one-third of the lymphocytes with chromosome damage carried multiple aberrations, suggesting that significant numbers of stem cells survive exposures to alpha-particle radiation that induce complex genomic alterations. Increased frequencies of GPA mutations were observed, demonstrating that genomic damage is also induced in erythroid progenitors. The numbers of micronuclei in lymphocytes were only moderately increased compared to expected values for persons of comparable age, and thus this end point was not useful for quantifying exposure level. Despite the relatively severe burden of somatic cell damage induced by 40 years of internal cr-particle irradiation, the patient remains surprisingly free of any serious illness. (C) 1997 by Radiation Research Society. C1 NCI, RADIAT EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. LOS ALAMOS NATL LAB, OCCUPAT MED GRP, LOS ALAMOS, NM 87545 USA. UNIV CALIF SAN FRANCISCO, SCH MED, DEPT LAB MED, SAN FRANCISCO, CA 94143 USA. INT EPIDEMIOL INST, ROCKVILLE, MD 20850 USA. RP Littlefield, LG (reprint author), OAK RIDGE INST SCI & EDUC, ENVIRONM & HLTH SCI DIV, OAK RIDGE, TN 37830 USA. FU PHS HHS [Y01-000501] NR 41 TC 22 Z9 22 U1 0 U2 0 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD AUG PY 1997 VL 148 IS 2 BP 135 EP 144 DI 10.2307/3579570 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA XP963 UT WOS:A1997XP96300005 PM 9254732 ER PT J AU Lucier, GW AF Lucier, GW TI Dose-response relationships for endocrine disruptors: What we know and what we don't know SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT ISRTP Meeting on Assessing the Risks of Adverse Endocrine-Mediated Effects CY JAN 13-14, 1997 CL RES TRIANGLE PK, NC SP Int Soc Regulatory Toxicol & Pharm RP Lucier, GW (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 5 Z9 5 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 1997 VL 26 IS 1 BP 34 EP 35 DI 10.1006/rtph.1997.1114 PN 1 PG 2 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA XZ586 UT WOS:A1997XZ58600005 PM 9339476 ER PT J AU Rogers, MJ Bukhman, YV McCutchan, TF Draper, DE AF Rogers, MJ Bukhman, YV McCutchan, TF Draper, DE TI Interaction of thiostrepton with an RNA fragment derived from the plastid-encoded ribosomal RNA of the malaria parasite SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE antibiotic; Plasmodium falciparum; ribosome; RNA hyperchromicity; transcription ID PLASMODIUM-FALCIPARUM; TERTIARY STRUCTURE; PROTEIN-SYNTHESIS; AMMONIUM ION; THERMODYNAMICS; ANTIBIOTICS; MICROCOCCIN; SEQUENCE; BINDING; SITES AB Although eukaryotes are not generally sensitive to thiostrepton, growth of the human malaria parasite Plasmodium falciparum is severely inhibited by the drug. The proposed target in P. falciparum is the ribosome of the plastid-like organelle (35 kb circular genome) of unknown function. Positive identification of the drug target would confirm that the organelle is essential for blood-stage development of Plasmodium and help clarify the plastid's biological role. The action of thiostrepton as an antibiotic relates to its affinity for a conserved domain of eubacterial rRNA. Its effect on organelles is unknown. Because a number of different point mutations within the Escherichia coli domain abrogates thiostrepton binding, extensive sequence differences between eubacterial and plastid domains brings into question the site of drug action. We have examined temperature-dependent hyperchromicity profiles of synthetic RNAs corresponding to domains in the plastid and cytoplasmic RNAs of P. falciparum. Thiostrepton induces a tertiary structure in the plastid-like fragment similar to that seen in eubacterial rRNA, even though the two share only about 60% sequence identity. A single point mutation in the plastid-like fragment removes thiostrepton-dependent tertiary structure formation. Thus, the plastid and eubacterial RNAs share a stabilized tertiary structure induced by the drug. This direct indicator of drug sensitivity in eubacteria suggests that the plastid-encoded ribosome is similarly sensitive to thiostrepton and that the plastid is the site of drug action. Correlation of thiostrepton-sensitive and -resistant phenotypes with physical parameters suggests thiostrepton resistance as a selectable marker for plastid transformation. C1 NIAID,GROWTH & DEV SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT CHEM,BALTIMORE,MD 21218. FU NIGMS NIH HHS [GM29048] NR 39 TC 39 Z9 41 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD AUG PY 1997 VL 3 IS 8 BP 815 EP 820 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XP329 UT WOS:A1997XP32900001 PM 9257641 ER PT J AU Coe, JE Ross, MJ AF Coe, JE Ross, MJ TI Electrophoretic polymorphism of a hamster pentraxin, female protein (amyloid P component) SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID C-REACTIVE PROTEIN; SYRIAN-HAMSTER; HUMAN-SERUM; ARMENIAN HAMSTER; CONSTITUENT; GENE AB Serum amyloid P protein (SAP) is a ubiquitous vertebrate protein distinguished by its conservative evolution and paucity of polymorphic forms. The SAP homologue in the Syrian hamster (Mesocricetus auratus), called Female Protein [FP(SAP)] is unique because its synthesis is controlled by sex hormones. These observations were limited to the commercially available standard Syrian hamsters that are descendants of three littermates captured in Syria in 1930., The authors examined FP(SAP) expression in nine inbred lines of Syrian hamsters that were derived from 12 wild hamsters captured in 1971. In general, regulation of FP(SAP) was similar in the new wild hamster strains, although a novel electrophoretically slower FP(SAP) was found in three of the strains, The slow FP(SAP) was not distinguished by size, antigenicity, binding capacity, or regulation. The electrophoretic difference was still apparent after deglycosylation. Hybrid offspring coexpressed both fast and slow FP monomers and formed a unique hybrid pentamer that had a new mobility between the fast and slow parent FP(SAP), The origin of this unusual polymorphism could be related to the amyloidogenesis associated with expression of FP(SAP) in the standard Syrian hamster. RP Coe, JE (reprint author), NIAID,ROCKY MT LAB,PERSISTENT VIRAL DIS LAB,NIH,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 27 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD AUG PY 1997 VL 46 IS 2 BP 180 EP 186 DI 10.1046/j.1365-3083.1997.d01-109.x PG 7 WC Immunology SC Immunology GA XN007 UT WOS:A1997XN00700011 PM 9583999 ER PT J AU Johnson, BE Cortazar, P Chute, JP AF Johnson, BE Cortazar, P Chute, JP TI Second lung cancers in patients successfully treated for lung cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID SMALL-CELL-CARCINOMA; LONG-TERM SURVIVORS; 2ND PRIMARY CANCERS; HODGKINS-DISEASE; PRIMARY TUMORS; RISK; CHEMOTHERAPY; RECURRENCE; RESECTION; FOLLOW C1 USN,MED RES INST,DEPT MED,DIV HEMATOL ONCOL,BETHESDA,MD 20889. RP Johnson, BE (reprint author), USN,MED RES INST,NCI,LUNG CANC BIOL SECT,MED BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. NR 47 TC 40 Z9 42 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1997 VL 24 IS 4 BP 492 EP 499 PG 8 WC Oncology SC Oncology GA XR607 UT WOS:A1997XR60700016 PM 9280229 ER PT J AU Rompalo, AM Shepherd, M Lawlor, JP Rand, S Fox, R Brookmeyer, R Quinn, TC Zenilman, J Hook, EW AF Rompalo, AM Shepherd, M Lawlor, JP Rand, S Fox, R Brookmeyer, R Quinn, TC Zenilman, J Hook, EW TI Definitions of genital ulcer disease and variation in risk for prevalent human immunodeficiency virus infection SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; INTRAVENOUS-DRUG-USERS; HIV-INFECTION; HOMOSEXUAL MEN; SAN-FRANCISCO; HERPES; TYPE-1; TRANSMISSION; ASSOCIATION; SEROCONVERSION AB Objectives: Although genital ulcer disease (GUD) has been associated with human immunodeficiency virus (HIV) infection in a number of studies, definitions of genital ulceration have varied. The authors hypothesized that the association of GUD with prevalent HIV infection may vary according to the definition of GUD that is used. Methods: As part of a prospective cohort study, 863 patients were interviewed and examined who presented to a sexually transmitted disease (STD) clinic for new symptom evaluation and who agreed to HIV testing to determine demographic and behavioral risk associated with prevalent HIV infection. To determine the association between GUD and prevalent HIV the following definitions of GUD were used: observed ulcers, history of syphilis, serologic evidence of syphilis, observed culture-proven genital herpes, and serologic evidence of herpes simplex virus type II (HSV-2) infection. Results: Of 481 men and 382 women enrolled, prevalent HN infection was detected in 12.5% and 5.2%, respectively. In multivariate analyses controlling for known HIV risk behaviors, prevalent HIV infection was associated with observed GUD (odds ratio [OR] = 2.0, 95% confidence intervals (CI)= 1.0-3.9), a history of syphilis (OR = 6.0, CI = 2.8-12.7), and serologic evidence of syphilis (OR = 3.7, CI = 1.9-7.0), but not with serologic evidence of HSV-2 (OR = 1.2, CI = 0.7-2.1), nor with observed HSV-2 culture-positive genital ulcerations (OR = 1.0, CI = 0.4-4.2), Factors contributing to different strengths of association between HIV infection and a history of syphilis or serologic evidence of syphilis included the presence of underdiagnosed syphilis infection in people with reactive serologic tests and the absence of serologic reactivity in people with a positive history. Conclusions: Although GUD is strongly associated with prevalent HIV, the strength of the association depends on the definition of GUD used. For accurate evaluation of people at risk for HIV, clinicians and researchers should use multiple definitions of GUD. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. BALTIMORE CITY DEPT HLTH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [5 RO1 AI27727] NR 35 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD AUG PY 1997 VL 24 IS 7 BP 436 EP 442 DI 10.1097/00007435-199708000-00009 PG 7 WC Infectious Diseases SC Infectious Diseases GA XP796 UT WOS:A1997XP79600009 PM 9263366 ER PT J AU Chen, YD Dougherty, ER AF Chen, YD Dougherty, ER TI Optimal and adaptive reconstructive granulometric bandpass filters SO SIGNAL PROCESSING LA English DT Article AB Granulometric spectral decomposition results from partitioning an image according to the manner in which a granulometry diminishes the image, An optimal granulometric bandpass filter is one that passes spectral components in a way to minimize the expected area of the symmetric difference between the filtered and ideal images. The present paper treats bandpass optimization for reconstructive granulometries. For these, each connected grain in the input image is either fully passed or eliminated, Such filters are well-suited for elimination of clutter or; equivalently, locating grains in size-shape bands. The observed image is typically modeled as a disjoint union of signal and clutter grains and the filter is designed to best eliminate clutter while maintaining the signal. The method is very general: grains are considered to be realizations of random sets; there are no shape constraints on signal and noise grains; there are no similarity constraints between granulometric and image generators; and the method applies to overlapping grains by filtering the image model resulting from segmentation preprocessing. Three filter design paradigms are considered, one for optimal and two for adaptive filters. (C) 1997 Elsevier Science B.V. C1 NIH,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. NR 12 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1684 J9 SIGNAL PROCESS JI Signal Process. PD AUG PY 1997 VL 61 IS 1 BP 65 EP 81 DI 10.1016/S0165-1684(97)00092-3 PG 17 WC Engineering, Electrical & Electronic SC Engineering GA XZ057 UT WOS:A1997XZ05700006 ER PT J AU Lambert, PA Somers, KD Kohn, EC Perry, RR AF Lambert, PA Somers, KD Kohn, EC Perry, RR TI Antiproliferative and antiinvasive effects of carboxyamido-triazole on breast cancer cell lines SO SURGERY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Society-of-University-Surgeons CY FEB 13-15, 1997 CL TAMPA, FL SP Soc Univ Surgeons ID CALCIUM INFLUX INHIBITOR; SIGNAL-TRANSDUCTION; BASEMENT-MEMBRANE; IV COLLAGENASE; INVITRO; ANGIOGENESIS; INVASIVENESS; METASTASIS; EXPRESSION; INVASION AB Background. Basement membrane invasion is one of the critical components of the metastatic cascade. The antiproliferative and antiinvasive activity of carboxyamido-triazole (CAI), a calcium influx inhibitor, was studied in five human breast cancer cell lines (MCF-7, MCF-7/ADR(R), MDA-231, MDA-231R44, and BT-474). Methods. Sensitivity of the cell lines to CAI was measured with a microculture tetrazolium assay. The Boyden chamber Matrigel chemoinvasion assay was used to measure the antiinvasive activity of CAI. Matrix metalloproteinase activity was analyzed by gelatin zymography. Results. The 50% inhibitory concentrations of CAI were cell line dependent and ranged from 7.49 +/- 4.05 mu mol/L to 46.1 +/- 8.6 mu mol/L. CAI at a low, minimally toxic concentration (5 mu mol/L) inhibited invasion by greater than 75% in the four invasive cell lines (MCF-7/ADR(R), MDA-231, MDA-231R44, and BT-474) regardless of estrogen receptor or p-glycoprotein status (p < 0.01). CAI treatment also reduced matrix metalloproteinase activity in conditioned media from three of the four invasive lines (p < 0.05). Conclusions. CAI at clinically achievable concentrations is an effective antiproliferative and antiinvasive agent against human breast cancer cell lines regardless of estrogen receptor or p-glycoprotein status. Reduction in matrix metalloproteinase activity may be partially responsible for CAI inhibition of invasion. C1 EASTERN VIRGINIA MED SCH,DIV SURG ONCOL,DEPT SURG,NORFOLK,VA 23507. EASTERN VIRGINIA MED SCH,DEPT MICROBIOL,NORFOLK,VA 23507. EASTERN VIRGINIA MED SCH,DEPT IMMUNOL,NORFOLK,VA 23507. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 25 TC 30 Z9 30 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1997 VL 122 IS 2 BP 372 EP 378 DI 10.1016/S0039-6060(97)90029-5 PG 7 WC Surgery SC Surgery GA XU463 UT WOS:A1997XU46300058 PM 9288143 ER PT J AU Pracyk, JB Hegland, DD Tanaka, K AF Pracyk, JB Hegland, DD Tanaka, K TI Effect of a dominant negative ras on myocardial hypertrophy by using adenoviral-mediated gene transfer SO SURGERY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Society-of-University-Surgeons CY FEB 13-15, 1997 CL TAMPA, FL SP Soc Univ Surgeons ID MUSCLE CELL HYPERTROPHY; DEPENDENT PATHWAYS; PROTEIN-KINASES; GROWTH; EXPRESSION; MYOCYTES; HEART AB Background. The small guanosine triphosphate-binding protein ras regulates a signal transduction cascade linking cell surface receptors to mitogen-activated protein kinase (MAPK). Because the molecular signaling mechanisms underlying cardiac hypertrophy remain unclear, the current study examined the regulatory role of ras in both the biochemical and morphologic aspects of hypertrophy. Methods. Adenoviral-mediated gene transfer was used to express a dominant negative mutant of ras (rasN17) at high efficiency in primary neonatal ventricular myocytes. Beta-galactosidase staining and Western blot analysis confirmed successful transfection and expression of the rasN17 gene product. MAPK activity was measured by an in vitro kinase assay resulting in radioactive Phosphorus labeled product. Morphologic hypertrophy was assessed by fluorescein-conjugated phalloidin. Results. Compared with uninfected or control adenoviral-infected cells, myocytes infected with rasN17 demonstrated attenuated basal MAPK activity. In contrast, rasN17 expression did not affect endothelin 1-induced MAPK activation. Morphologic studies showed that although rasN17 produced a phenotypic difference in the basal state, the ability of cardiac myocytes to morphologically respond to endothelin 1 stimulation, as manifested by sarcomeric reorganization remained unaltered by the expression of the rasN17 gene product. Conclusions. Endothelin 1-stimulated MAPK activation and endothelin 1-induced morphologic hypertrophy are ras-independent processes. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NATL INST GEN MED SCI,PHARMACOL RES ASSOCIATE PROGRAM,NIH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DEPT SURG,DALLAS,TX 75235. NR 18 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1997 VL 122 IS 2 BP 404 EP 410 DI 10.1016/S0039-6060(97)90033-7 PG 7 WC Surgery SC Surgery GA XU463 UT WOS:A1997XU46300066 PM 9288147 ER PT J AU Musachio, JL Villemagne, VL Scheffel, U Stathis, M Finley, P Horti, A London, ED Dannals, RF AF Musachio, JL Villemagne, VL Scheffel, U Stathis, M Finley, P Horti, A London, ED Dannals, RF TI [I-125/123]IPH: A radioiodinated analog of epibatidine for in vivo studies of nicotinic acetylcholine receptors SO SYNAPSE LA English DT Article DE iodine-123; iodine-125; epibatidine; nicotinic acetylcholine receptor; SPECT ID POSITRON EMISSION TOMOGRAPHY; IN-VIVO; CHOLINERGIC RECEPTORS; HUMAN BRAIN; ALPHA-BUNGAROTOXIN; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; BINDING-SITES; H-3 CYTISINE; MOUSE-BRAIN AB Tomographic imaging of central nicotinic acetylcholine receptors (nAChRs) via single photon emission computed tomography (SPECT) has been hampered by the lack of a radioligand with suitable in vivo binding characteristics. Therefore, a novel analog of epibatidine, (+/-)-exo-2-(2-iodo-5-pyridyl)-7-azabicyclo [2.2.1]heptane (IPH), labeled with [I-125] or [I-123] was evaluated as an in vivo marker of central nicotinic acetylcholine receptors (nAChRs). [I-125]IPH showed substantial brain penetration (4.2% of the injected dose at 30 min) and a cerebral biodistribution in mice consistent with the in vivo labeling of nAChRs (% injected dose/gram of thalamus, superior colliculi >> cerebellum). [I-125]IPH binding sites were shown to be saturable with unlabeled IPH (ED50 approximately 1 mu g/kg). The uptake of [I-125]IPH was blocked significantly by the nicotinic agonists, cytisine, lobeline, and (-)-nicotine, but not by the noncompetitive nAChR antagonist, mecamylamine. Antagonists of muscarinic (scopolamine), serotonin (ketanserin), and opioid (naloxone) receptors had no significant effect on [I-125]IPH binding. A preliminary SPECT imaging study with [I-123]IPH in a baboon showed [I-123]IPH to localize in nAChR-rich areas of brain (thalamus > frontal cortex > cerebellum). [I-123]IPH binding in baboon brain was also displaced (35-45% displacement) by a challenge dose of cytisine showing that a well-characterized nicotinic agonist effectively competes for [I-123]IPH binding sites. [I-123]IPH seems well suited for imaging studies of nAChRs and, to our knowledge, is the first SPECT agent that has allowed for the visualization of nAChRs in primate brain. (C) 1997 Wiley-Liss, Inc. C1 JOHNS HOPKINS MED INST,DEPT RADIOL,DIV NUCL MED,BALTIMORE,MD 21287. NIDA,BRAIN IMAGING SECT,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. NR 41 TC 61 Z9 62 U1 1 U2 2 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 AUG PY 1997 VL 26 IS 4 BP 392 EP 399 DI 10.1002/(SICI)1098-2396(199708)26:4<392::AID-SYN7>3.0.CO;2-1 PG 8 WC Neurosciences SC Neurosciences & Neurology GA XJ056 UT WOS:A1997XJ05600007 PM 9215598 ER PT J AU Kohler, HP Boothby, M McCormack, L Knowler, WC Gant, PJ AF Kohler, HP Boothby, M McCormack, L Knowler, WC Gant, PJ TI Incidence of Arg506->Gln mutation (factor V Leiden) in Pima Indians SO THROMBOSIS AND HAEMOSTASIS LA English DT Letter ID ACTIVATED PROTEIN-C; COAGULATION-FACTOR-V; VENOUS THROMBOSIS; RESISTANCE; STROKE C1 NIDDKD,PHOENIX,AZ. RP Kohler, HP (reprint author), GEN INFIRM,DIV MED,UNIT MOL VASC MED,G FLOOR,MARTIN WING,LEEDS LS1 3EX,W YORKSHIRE,ENGLAND. NR 14 TC 8 Z9 8 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1997 VL 78 IS 2 BP 961 EP 962 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA XQ021 UT WOS:A1997XQ02100035 PM 9268205 ER PT J AU Tsutsui, T Tanaka, Y Ushimura, A Ide, T Matsumura, M Barrett, JC AF Tsutsui, T Tanaka, Y Ushimura, A Ide, T Matsumura, M Barrett, JC TI In vitro cytotoxicity of diverse preparations used in dental practice to human gingival keratinocytes SO TOXICOLOGY IN VITRO LA English DT Article ID CHROMOSOME-ABERRATIONS; TOXICITY AB The cytotoxicities of diverse preparations used for dental practice were examined with normal human keratinocytes from gingival tissues by the uptake of neutral red (NR assay). Cultures from different individuals were established, and secondary cultures in serum-free medium were used. The cytotoxicities to cells treated for 2 days with gargles, mouthwashes, gingival massages, fluoride preparations, dentifrices and local anaesthetics were determined from the dose-response curves of inhibition of NR uptake. As a quantitative measure of cytotoxicity, NR50 (the concentration of the preparations that resulted in a 50% decrease in NR uptake relative to untreated controls) was interpolated from dose-response curves. Dentifrices examined showed cytotoxicity similar to gingival massages but were more cytotoxic than any fluoride preparations, local anaesthetics, and most gargles and mouthwashes. The cytotoxicities of dentifrices were at least 6.5-fold those of fluoride preparations and 7.9-fold those of local anaesthetics. The results provide useful estimates of relative toxicities of dental preparations to human oral mucosa and are useful as a standard for cytotoxic assessment of newly developed preparations for dental use. Published by Elsevier Science Ltd. C1 NIPPON DENT UNIV TOKYO,DEPT PHARMACOL,SCH DENT,CHIYODA KU,TOKYO 102,JAPAN. NIEHS,MOL CARCINOGENESIS LAB,ENVIRONM CARCINOGENESIS PROGRAM,NIH,RES TRIANGLE PK,NC 27709. NR 11 TC 1 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD AUG PY 1997 VL 11 IS 4 BP 393 EP 398 DI 10.1016/S0887-2333(97)00030-1 PG 6 WC Toxicology SC Toxicology GA XV797 UT WOS:A1997XV79700009 PM 20654326 ER PT J AU Hengen, PN AF Hengen, PN TI Chemiluminescent detection methods SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID DNA; BLOTS AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses some tips for using chemiluminescent detection methods. For details on how to partake in the newsgroup, see the accompanying box. RP Hengen, PN (reprint author), FREDERICK CANC RES & DEV CTR,NCI,FREDERICK,MD 21702, USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1997 VL 22 IS 8 BP 313 EP 314 DI 10.1016/S0968-0004(97)01095-5 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XR128 UT WOS:A1997XR12800012 PM 9270305 ER PT J AU Carroll, RG Riley, JL Levine, BL Kaushal, S Bernstein, W StLouis, DC June, CH Berger, EA AF Carroll, RG Riley, JL Levine, BL Kaushal, S Bernstein, W StLouis, DC June, CH Berger, EA TI Control of HIV co-receptor expression: Implications for pathogenesis and treatment - Response SO TRENDS IN MICROBIOLOGY LA English DT Article ID CD28 C1 NIAID,NIH,BETHESDA,MD 20892. RP Carroll, RG (reprint author), WALTER REED ARMY INST RES,ROCKVILLE,MD 20850, USA. RI Levine, Bruce/D-1688-2009 NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD AUG PY 1997 VL 5 IS 8 BP 302 EP 303 DI 10.1016/S0966-842X(97)01093-7 PG 2 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA XQ007 UT WOS:A1997XQ00700004 ER PT J AU Hackstadt, T AF Hackstadt, T TI The chlamydial inclusion membrane as an engine of survival - Response SO TRENDS IN MICROBIOLOGY LA English DT Letter ID CELLS; MACROPHAGES; PSITTACI RP Hackstadt, T (reprint author), NIAID,ROCKY MT LABS,HOST PARASITE INTERACT SECT,INTRACELLULAR PARASITES LAB,NIH,HAMILTON,MT 59840, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD AUG PY 1997 VL 5 IS 8 BP 305 EP 306 DI 10.1016/S0966-842X(97)82225-1 PG 2 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA XQ007 UT WOS:A1997XQ00700007 ER PT J AU Walther, MM Delaney, TF Smith, PD Friauf, WS Thomas, GF Shawker, TH Vargas, MP Choyke, PL Linehan, WM Abraham, EH Okunieff, PG Glatstein, E AF Walther, MM Delaney, TF Smith, PD Friauf, WS Thomas, GF Shawker, TH Vargas, MP Choyke, PL Linehan, WM Abraham, EH Okunieff, PG Glatstein, E TI Phase I trial of photodynamic therapy in the treatment of recurrent superficial transitional cell carcinoma of the bladder SO UROLOGY LA English DT Article ID PHOTORADIATION THERAPY; LIGHT DOSIMETRY; TUMORS; CANCER; EXPERIENCE; DIAGNOSIS; INSITU; OXYGEN; SITU AB Objectives. A Phase I trial of photodynamic therapy (PDT) in the treatment of superficial transitional cell carcinoma (TCC) of the bladder was performed. Methods. Twenty patients with recurrent superficial TCC of the bladder after receiving a mean of 2.6 (range 1 to 6) courses of intravesical therapy were treated with PDT. Tt ie photosensitizer Photofrin II dose was 1.5 or 2.0 mg/kg. A 650-nm intravesical red laser was used to activate the photosensitizer 2 days after administration of Photofrin II. A 0.01% intralipid solution was used as a bladder-filling medium to scatter light and achieve more homogeneous light distribution. Light doses from 5.1 to 25.6 J/cm(2) (total dosage 1500 to 5032 J) were used to illuminate the bladder. Results. Twenty patients underwent 21 treatments with PDT. Complications included asymptomatic reflux in 4 patients. One other patient, treated at the highest total light dose, experienced bladder contraction and fibrosis. Nine patients (45%) had no tumor evident at cystoscopy, on random biopsies, or in urinary cytology at the 3-month evaluation after treatment. Four patients remained without recurrent disease for 23 to 56 months. Sixteen of 20 (80%) patients experienced recurrence, and 8 of the 16 underwent cystectomy. Conclusions. An intravenous photosensitizer dose of 1.5 mg/kg Photofrin II followed by light energy in the range of 15 J/cm(2) (total light dose 2500 to 3250 J) was defined as a safe treatment parameter and resulted in tumor responses. With present technologies, administration of PDT requires careful dosimetry. C1 NIH,NATL CTR RES RESOURCES,UROL ONCOL BRANCH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENT BRANCH,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP Walther, MM (reprint author), NCI,UROL ONCOL BRANCH,DSC,DEPT PATHOL,NIH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2B-43,10 CTR DR,BETHESDA,MD 20898, USA. NR 39 TC 23 Z9 25 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD AUG PY 1997 VL 50 IS 2 BP 199 EP 206 DI 10.1016/S0090-4295(97)00211-2 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA XP368 UT WOS:A1997XP36800008 PM 9255289 ER PT J AU Walther, MM Kleiner, DE Lubensky, IA Pozzatti, R Nyguen, T Gnarra, JR Hurley, K Venzon, D Linehan, WM StetlerStevenson, WG AF Walther, MM Kleiner, DE Lubensky, IA Pozzatti, R Nyguen, T Gnarra, JR Hurley, K Venzon, D Linehan, WM StetlerStevenson, WG TI Progelatinase A mRNA expression in cell lines derived from tumors in patients with metastatic renal cell carcinoma correlates inversely with survival SO UROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; MATRIX METALLOPROTEINASE INHIBITOR; IV COLLAGENASE; TRANSFORMING GROWTH-FACTOR-BETA-1; INVASION; ADENOCARCINOMA; DEGRADATION; GELATINASES; FIBROBLASTS; POTENTIALS AB Objectives. Tumors are thought to metastasize by a process involving tumor cell attachment to extracellular matrix, degradation of matrix components by tumor-associated proteases, and cellular movement into the area modified by protease activity. Type IV collagen comprises the major element tumor cells must degrade to gain access to the rest of the body. Renal cancer cell line progelatinase A (E.C. 3.4.24.24; 72-kDa type IV collagenase; MMP-2) mRNA expression was correlated with patient survival. Methods. Total cellular mRNA was extracted from tumor cell lines derived from patients with metastatic renal cell carcinoma. The results of the densitometric analysis of Northern blots were correlated with patient survival. Formalin-fixed, paraffin-embedded tissue sections of primary renal cancers were examined for immunohistochemical expression of MMP-2. Results. Cell lines established from 23 primary renal tumors and six metastatic sites in 26 patients with metastatic renal carcinoma were studied. Variable expression of progelatinase A, relative to A2058 melanoma cells (mean +/- SEM, 0.60 +/- 0.21; median, 0.082; range, 0 to 4.78), was found. There was a significant inverse association between patient survival and the log of the MMP-2 expression (P = 0.045 by the Cox proportional-hazards model). Using a cutoff value of 0.10, the closest round number to the median expression of MMP-2, a significant difference between survival of patients with lower and higher MMP-2 expression in their primary renal cell line was found (P = 0.0054). Cell lines with low, intermediate, and high expression of MMP-2 mRNA all had primary tumors with high tissue immunohistochemical expression of MMP-2. Conclusions. These studies demonstrate an inverse relationship between renal cancer cell line MMP-2 mRNA expression and patient survival. Immunohistochemical studies of the primary tumors from which the cell lines were derived uniformly showed high MMP-2 expression. Previous work suggests local renal factors upregulate cellular expression of MMP-2 in the primary tumor, and are not active at extrarenal sites. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,COP,DCT,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,COP,DCT,NIH,BETHESDA,MD 20892. RP Walther, MM (reprint author), NCI,UROL ONCOL BRANCH,DCS,NIH,COP,DCT,BLDG 10,ROOM 2B-43,10 CTR DR MSC 1502,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008; Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Kleiner, David/0000-0003-3442-4453 NR 34 TC 21 Z9 21 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD AUG PY 1997 VL 50 IS 2 BP 295 EP 301 DI 10.1016/S0090-4295(97)00220-3 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA XP368 UT WOS:A1997XP36800029 PM 9255309 ER PT J AU Chuaqui, RF Englert, CR Strup, SE Vocke, CD Zhuang, ZP Duray, PH Bostwick, DG Linehan, WM Liotta, LA EmmertBuck, MR AF Chuaqui, RF Englert, CR Strup, SE Vocke, CD Zhuang, ZP Duray, PH Bostwick, DG Linehan, WM Liotta, LA EmmertBuck, MR TI Identification of a novel transcript up-regulated in a clinically aggressive prostate carcinoma SO UROLOGY LA English DT Article ID HUMAN BREAST-CANCER; CLONING AB Objectives. To identify differentially expressed genes in tumor cells of patients with prostate cancer by means of tissue microdissection and targeted differential display. Methods. RNA was recovered from pure populations of microdissected normal epithelium and invasive tumor from frozen tissue sections of a radical prostatectomy specimen. Reverse transcriptian-polymerase chain reaction (PCR) using arbitrary and zinc finger PCR primers was performed. Results, A 130-base pair product was identified that appeared selectively in the tumor sample. DNA sequence analysis revealed it to be a clone from the expressed sequence tag database (GenBank accession R00504). Microdissection of normal epithelium and the corresponding invasive tumor was subsequently performed on a test panel of 10 prostate carcinoma specimens. Comparison of R00504 levels in normal epithelium and invasive carcinoma, using beta-actin as an internal control, showed the transcript to be substantially overexpressed in 5 of 10 carcinomas. Northern blotting revealed R00504 to be a 2.6-kilobase gene. Conclusions. A navel transcript up-regulated in an aggressive prostate carcinoma was identified using degenerate zinc finger primers in microdissected tissue samples. The approach used in this study may be helpful in quantitative comparison of known genes and identification of novel gel?es in microdissected human tissue samples. (C) 1997, Elsevier Science Inc. All rights reserved. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,DEPT PATHOL,ROCHESTER,MN 55905. NR 16 TC 32 Z9 35 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD AUG PY 1997 VL 50 IS 2 BP 302 EP 307 DI 10.1016/S0090-4295(97)00194-5 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA XP368 UT WOS:A1997XP36800030 PM 9255310 ER PT J AU Zhang, C Cornette, JL Berzofsky, JA DeLisi, C AF Zhang, C Cornette, JL Berzofsky, JA DeLisi, C TI The organization of human leucocyte antigen class I epitopes in HIV genome products: implications for HIV evolution and vaccine design SO VACCINE LA English DT Article DE anchor residue motif; T-cell epitopes; r-scan statistics; antigenic variation ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; ALLELE-SPECIFIC MOTIFS; ENDOGENOUS PEPTIDES; 3-DIMENSIONAL STRUCTURE; ENVELOPE GLYCOPROTEIN; MASS-SPECTROMETRY; PROTEIN SEQUENCES; GENETIC-VARIATION; CRYSTAL-STRUCTURE AB Knowledge of human leucocyte antigen (HLA) peptide binding motifs permits rapid selection of candidate viral protein fragments for induction of T cell-mediated immunity. A search for HLA class I peptide binding motifs in structural proteins of human immunodeficiency virus (HIV) of different genetic lineages provides a map of the genetic organization of potential T cell antigenic sites, and at the same time identifies all motifs in highly conserved regions of HIV-1 env, gag and pol. The density of motifs is anomalous at both the high and low end of the spectrum: local organization is characterized by anomalously long runs between motifs. The former is expected simply due to the fact that motifs often have overlapping anchor residue sets. A detailed statistical analysis of the latter, however, shows that the length of the runs cannot be accounted for by chance alone. Although motif clusters show no preference to be in either conserved or variable regions, low motif density stretches occur preferentially in variable portions of the protein sequence, which suggests that the virus may be mutating to evade the cellular arm of the immune system. (C) 1997 Elsevier Science Ltd. C1 BOSTON UNIV,DEPT BIOMED ENGN,BOSTON,MA 02215. IOWA STATE UNIV,DEPT MATH,AMES,IA 50011. NCI,MOL IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI30535] NR 65 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD AUG-SEP PY 1997 VL 15 IS 12-13 BP 1291 EP 1302 DI 10.1016/S0264-410X(97)00040-6 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XV342 UT WOS:A1997XV34200002 PM 9302734 ER PT J AU Yang, ST Carroll, MW TorresDuarte, AP Moss, B Davidson, EA AF Yang, ST Carroll, MW TorresDuarte, AP Moss, B Davidson, EA TI Addition of the MSA1 signal and anchor sequences to the malaria merozoite surface antigen 1 C-terminal region enhances immunogenicity when expressed by recombinant vaccinia virus SO VACCINE LA English DT Article DE malaria vaccine; merozoite surface antigen 1; vaccinia virus ID PLASMODIUM-FALCIPARUM MEROZOITES; PROTECTS AOTUS MONKEYS; HUMAN-ERYTHROCYTES; SAIMIRI MONKEYS; ENVELOPE GENE; PROTEIN-1; IMMUNITY; PRECURSOR; VECTOR; DNA AB Genes encoding four different C-terminal fragments of a Plasmodium falciparum merozoite surface antigen were generated: MSA1C-(Si,A), containing signal and anchor; MSA1C-(nSi,A), containing the anchor but not the signal, and MSA1C-(nSi,nA) containing neither the signal nor the anchor region. Each gene was inserted into the thymidine kinase region of vaccinia virus, under the control of a synthetic strong early/late promoter. When the plasmodial genes were expressed in cells infected by the recombinant vaccinia virus, the two proteins containing the signal region were transported to the surface of infected cells. Infection of mice and rabbits with the latter recombinant viruses stimulated C-terminal-specific antibody levels that were 10-80-fold higher than those induced by the two recombinant viruses with the signal region. The combination of the signal and anchor regions with the C-terminal MSA1 protein also generated the most effective neutralization in a P. falciparum invasion assay. (C) 1997 Published by Elsevier Science Ltd. C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. NIAID,VIRAL DIS LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 44 TC 9 Z9 11 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD AUG-SEP PY 1997 VL 15 IS 12-13 BP 1303 EP 1313 DI 10.1016/S0264-410X(97)00039-X PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XV342 UT WOS:A1997XV34200003 PM 9302735 ER PT J AU Murphy, BR Park, EJ Gottlieb, P Subbarao, K AF Murphy, BR Park, EJ Gottlieb, P Subbarao, K TI An influenza A live attenuated reassortant virus possessing three temperature-sensitive mutations in the PB2 polymerase gene rapidly loses temperature sensitivity following replication in hamsters SO VACCINE LA English DT Article DE influenza virus; vaccine; temperature-sensitive mutants; PB2 gene ID A VIRUS; SQUIRREL-MONKEYS; AVIAN-HUMAN; NEURAMINIDASE; VACCINES; VIRULENCE; MUTANT; IMMUNOGENICITY; DETERMINANTS; CHIMPANZEES AB The purpose of the present study was to produce an influenza A H2N2 donor virus from which an attenuating PB2 gene bearing three discrete temperature sensitive (ts) mutations could be readily transferred to currently epidemic influenza A H1N1 and H3N2 viruses via genetic reassortment. An influenza A transfectant virus was first produced that contained site-directed ts mutations at amino acids 112, 265, and 556 in the PB2 gene of influenza A/AA/60 virus origin in a background of the other seven RNA segments fron the influenza A/LA/87 (H3N2) virus. The A/LA/87 PB2 is transfectant virus (clone 22B1) was mated with the A/AA/60 (H2N2) wild type virus, and six H2N2 is reassortants were obtained. One reassortant virus, clone 25Al, possessed the triple ts PB2 gene in the context of all seven other genes of homologous A/AA/60 origin. Isolation of this reassortment permitted an examination of the contribution of the ts PB2 transfectant virus to its attenuation and phenotypic stability independent from an effect of the A/AA/60-A/LA/87 gene constellation on attenuation, and less phenotypically stable than the A/LA/87 triple ts transfectant virus from which it was derived. The A/AA/60 reassortment possessing the PB2 gene containing three introduced ts mutations underwent rapid and significant loss of its temperature sensitivity following replication in the lungs of immunocompetent hamsters. This indicated that the A/AA/60-A/LA/87 gene constellation contributed significantly to the overall level of temperature-sensitivity, attenuation, and stability of the A/LA/87 triple is transfectant virus. It is likely that the instability of the ts phenotype exhibited by the A/AA/60 triple ts reassortment virus would not be acceptable for a vaccine to be used in humans. The implications of these findings for the usefulness of ts mutations as the sole attenuating mutation in influenza virus vaccines is discussed. Published by Elsevier Science Ltd. RP Murphy, BR (reprint author), NIAID,INFECT DIS LAB,NIH,7 CTR DR,MSC 0720,BETHESDA,MD 20892, USA. NR 28 TC 31 Z9 33 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD AUG-SEP PY 1997 VL 15 IS 12-13 BP 1372 EP 1378 DI 10.1016/S0264-410X(97)00031-5 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XV342 UT WOS:A1997XV34200015 PM 9302747 ER PT J AU Walther, MM Cutler, GB AF Walther, MM Cutler, GB TI Urodynamic abnormalities in two brothers with adrenomyeloneuropathy SO WORLD JOURNAL OF UROLOGY LA English DT Article ID PEROXISOMAL DISORDERS; PROBABLE VARIANT; ADRENOLEUKODYSTROPHY AB Adrenoleukodystrophy is an X-linked disorder characterized by loss of adrenal function and demyelinating nervous disease. A slowly progressive form, adrenomyeloneuropathy, has been described that can mimic multiple sclerosis. Two brothers are presented whose contrasting urodynamic findings are compatible with upper and mixed (upper and lower) motor neuron disease, respectively. C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. RP Walther, MM (reprint author), NCI,DCS,UROL ONCOL BRANCH,NIH,10 CTR DR,MSC 1502,BETHESDA,MD 20898, USA. NR 11 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD AUG PY 1997 VL 15 IS 4 BP 262 EP 265 DI 10.1007/BF01367665 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA XR432 UT WOS:A1997XR43200009 PM 9280056 ER PT J AU Turkel, S Liao, XB Farabaugh, PJ AF Turkel, S Liao, XB Farabaugh, PJ TI GCR1-dependent transcriptional activation of yeast retrotransposon Ty2-917 SO YEAST LA English DT Article DE yeast retrotransposon; GCR1; transcription ID SACCHAROMYCES-CEREVISIAE ENCODES; GLYCOLYTIC GENE-EXPRESSION; DNA-BINDING PROTEIN; TRANSPOSABLE ELEMENT; CHROMATIN STRUCTURE; DEHYDROGENASE GENE; REGULATORY ELEMENT; SEQUENCE; UPSTREAM; COMPLEX AB Transcription of Saccharomyces cerevisiae Ty2-917 retrotransposon depends on regulatory elements both upstream and downstream of the transcription initiation site. An upstream activation sequence (UAS) and a downstream enhancer stimulate transcription synergistically. Here we show that activation by both of these sites depends on the GCR1 product, a transcription factor which also regulates the genes encoding yeast glycolytic enzymes. Eliminating GCR1 causes a 100-fold decrease in transcription of Ty2-917. Activation by the isolated Ty2-917 UAS also strongly depends on GCR1. Unexpectedly, GCR1-dependent activation by the Ty2-917 enhancer is strongly position-dependent. Activation by the enhancer in its normal position within the transcription unit depended strongly on GCR1, but eliminating GCR1 reduced activation only three-fold when the enhancer was moved upstream of the transcribed region. Gel mobility shift and DNaseI protection assays indicated that GCR1 binds specifically to multiple sites within the Ty2-917 UAS and enhancer regions. (C) 1997 by John Wiley & Sons, Ltd. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. UNIV MARYLAND,DEPT SCI BIOL,BALTIMORE,MD 21228. UNIV MARYLAND,MOL & CELLULAR BIOL PROGRAM,BALTIMORE,MD 21228. RP Turkel, S (reprint author), ABANT IZZET BAYSAL UNIV,FAC ARTS & SCI,DEPT BIOL,TR-14280 BOLU,TURKEY. FU NIGMS NIH HHS [GM-29480] NR 61 TC 22 Z9 23 U1 2 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD AUG PY 1997 VL 13 IS 10 BP 917 EP 930 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA XQ153 UT WOS:A1997XQ15300003 PM 9271107 ER PT J AU Alberdi, E Becerra, SP AF Alberdi, E Becerra, SP TI Heparin and heparan sulfate with affinity for the neurotrophic factor PEDF. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1386 BP A1094 EP A1094 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601872 ER PT J AU Allan, CB Stadtman, TC AF Allan, CB Stadtman, TC TI Mechanistic studies of a tRNA-modifying enzyme that catalyzes the replacement of sulfur in 2-thiouridine nucleotides with selenium SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 940 BP A1019 EP A1019 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601426 ER PT J AU Allison, KC Henkart, PA AF Allison, KC Henkart, PA TI Enhancement of phagocytosis of apoptotic cells by serum SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, EIB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2250 BP A1241 EP A1241 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602737 ER PT J AU Amin, ND Pant, HC AF Amin, ND Pant, HC TI Functional domains of p35 that activate neuronal cyclin dependent kinase-5 (CDK5) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1912 BP A1184 EP A1184 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602399 ER PT J AU Anderson, HA Roche, PA AF Anderson, HA Roche, PA TI Phosphorylation of invariant chain occurs on serine residues 26 and 29 by a kinase activity associated with professional antigen presenting cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1192 BP A1061 EP A1061 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601680 ER PT J AU Arya, SK AF Arya, SK TI HIV-2 lentivirus vectors for gene transfer SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Natl Canc Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 733 BP A982 EP A982 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601220 ER PT J AU Baier, LJ Wiedrich, C Hanson, RL Bogardus, C AF Baier, LJ Wiedrich, C Hanson, RL Bogardus, C TI Association of Met -> Ile substitution in the regulatory subunit of PI3 kinase with non-insulin dependent diabetes mellitus (NIDDM) in Pima women. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2864 BP A1347 EP A1347 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603349 ER PT J AU Bailey, AL Chernomordik, LV AF Bailey, AL Chernomordik, LV TI Lipid effects in liposome cell fusion mediated by influenza hemagglutinin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Cellular & Mol Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1219 BP A1065 EP A1065 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601703 ER PT J AU Balagurumoorthy, P Appella, E Harrington, RE AF Balagurumoorthy, P Appella, E Harrington, RE TI Flexibility/bending in the p53 response elements and its biological implications SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Nevada, Reno, NV 89557 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2296 BP A1249 EP A1249 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602783 ER PT J AU Barclay, TB Peters, JM Gonzalez, FJ Sewer, MB Morgan, ET AF Barclay, TB Peters, JM Gonzalez, FJ Sewer, MB Morgan, ET TI PPAR alpha mediates induction of P450 4A10 in endotoxin-stimulated mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Atlanta, GA USA. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P193 BP A804 EP A804 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600195 ER PT J AU Basi, NS Rebois, RV AF Basi, NS Rebois, RV TI GTP analogs differ in their ability to promote G delta subunit dissociation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Membrane Biochem Sect, LMCN, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1121 BP A1049 EP A1049 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601606 ER PT J AU Berger, EA AF Berger, EA TI Chemokine receptors: Doors for HIV entry and windows on transmission and pathogenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, NIAID, Viral Dis Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 57 BP A867 EP A867 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600544 ER PT J AU Biagini, C Celier, C Carver, G Philpot, R AF Biagini, C Celier, C Carver, G Philpot, R TI Coexpression of cytochrome P450 2C11 and NADPH-P450 oxidoreductase in insect cells allows structure-function relationship analyses. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. INSERM U75, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P121 BP A792 EP A792 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600124 ER PT J AU Bos, MP Grunert, F Belland, RJ AF Bos, MP Grunert, F Belland, RJ TI Differential recognition of carcinoembryonic antigens by Opa variants of Neisseria gonorrhoeae SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Freiburg, Inst Immunobiol, D-7800 Freiburg, Germany. NIAID, NIH, Rocky Mt Labs, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3409 BP A1439 EP A1439 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603894 ER PT J AU Brosh, RM Balajee, AS Bischoff, C Evans, MK Machwe, A Nehlin, JO Orren, DK Bohr, VA AF Brosh, RM Balajee, AS Bischoff, C Evans, MK Machwe, A Nehlin, JO Orren, DK Bohr, VA TI Investigation of the molecular defects in premature aging syndromes. Functional analysis of the sequence-related CSB and WRN proteins. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1970 BP A1194 EP A1194 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602455 ER PT J AU Bryant, SH AF Bryant, SH TI Structure prediction by protein threading SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1562 BP A1124 EP A1124 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602047 ER PT J AU Burkholder, WF Zhu, ZX Hendrickson, WA Gragerov, A Gottesman, ME AF Burkholder, WF Zhu, ZX Hendrickson, WA Gragerov, A Gottesman, ME TI Mutational analysis of substrate binding by the molecular chaperone DnaK. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 295 BP A908 EP A908 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600784 ER PT J AU Butscher, W Powers, C Vinson, C Gardner, K AF Butscher, W Powers, C Vinson, C Gardner, K TI Coordinate transactivation of the CD28 response element of the interleukin-2 promoter by C-Rel and ATF-1/CREB2. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2036 BP A1205 EP A1205 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602520 ER PT J AU Cabaniols, JP Ravichandran, V Valdez, A Roche, PA AF Cabaniols, JP Ravichandran, V Valdez, A Roche, PA TI Identification and characterization of a "SNARE kinase" SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1190 BP A1060 EP A1060 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601676 ER PT J AU Caffrey, JJ Craxton, A Shears, SB AF Caffrey, JJ Craxton, A Shears, SB TI Molecular cloning and characterization of rat hepatic multiple inositol polyphosphate phosphatase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2887 BP A1351 EP A1351 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603375 ER PT J AU Cain, SA Padlan, EA Helm, BA AF Cain, SA Padlan, EA Helm, BA TI Expression of the IgE high affinity receptor in Pichia pastoris SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Sheffield, Krebs Inst, Dept Molbiol & Biotech, Sheffield S10 2UH, S Yorkshire, England. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1789 BP A1163 EP A1163 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602273 ER PT J AU Casas-Finet, JR Urbaneja, MA Nower, PN Gorelick, RJ Bosche, WJ Kane, BP Johnson, DJ Henderson, LE AF Casas-Finet, JR Urbaneja, MA Nower, PN Gorelick, RJ Bosche, WJ Kane, BP Johnson, DJ Henderson, LE TI Functional properties of point-mutated MoMuLV nucleocapsid (NC) protein p10. SO FASEB JOURNAL LA English DT Meeting Abstract C1 SAIC, AVP, Frederick, MD USA. NCI, FCRDC, Frederick, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 729 BP A981 EP A981 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601215 ER PT J AU Castagnino, P Bottaro, DP AF Castagnino, P Bottaro, DP TI Identification of tissue inhibitor of metalloproteinases-3 as a gene induced by hepatocyte growth factor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2772 BP A1332 EP A1332 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603259 ER PT J AU Chae, HZ Kang, SW Kim, HJ Kim, K Baines, IC Rhee, SG AF Chae, HZ Kang, SW Kim, HJ Kim, K Baines, IC Rhee, SG TI Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin and their role in signal transduction SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 981 BP A1025 EP A1025 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601467 ER PT J AU Chao, CC Stadtman, ER AF Chao, CC Stadtman, ER TI Decreased activity of antioxidant enzymes in human fibroblasts from old donors. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2352 BP A1259 EP A1259 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602838 ER PT J AU Clark, JA AF Clark, JA TI Analysis of the transmembrane topology and membrane assembly of the GAT-1 GABA transporter. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Genet Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 661 BP A970 EP A970 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601148 ER PT J AU Clark, WA Chen, L Northup, JK AF Clark, WA Chen, L Northup, JK TI Analysis of G-protein-receptor interactions by surface plasmon resonance using immobilized receptor. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1149 BP A1054 EP A1054 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601635 ER PT J AU Collins, FS AF Collins, FS TI Genome analysis and cancer susceptibility SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2588 BP A1301 EP A1301 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603075 ER PT J AU Craigie, R AF Craigie, R TI Integration of HIV DNA into the host cell genome SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, NIDDK, Mol Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 59 BP A867 EP A867 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600545 ER PT J AU Davis, DA Newcomb, FM Starke, DW Ott, DE Mieyal, JJ Yarchoan, R AF Davis, DA Newcomb, FM Starke, DW Ott, DE Mieyal, JJ Yarchoan, R TI Glutathionylated forms of the HIV-1 protease are substrates for human thioltransferase (glutaredoxin), an enzyme also detected in HIV-1 virions SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, HAMB, Bethesda, MD 20892 USA. Frederick Canc Res & Dev Ctr, SAIC, AIDS Vaccine Program, Frederick, MD 21702 USA. Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 735 BP A982 EP A982 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601221 ER PT J AU DebBurman, SK Raymond, GJ Caughey, B Lindquist, SL AF DebBurman, SK Raymond, GJ Caughey, B Lindquist, SL TI Chaperone-mediated conversion of cellular prion protein PrP-C to its protease-resistant form. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 290 BP A907 EP A907 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600776 ER PT J AU Ding, L Zhang, YH Sun, P Coleman, WG AF Ding, L Zhang, YH Sun, P Coleman, WG TI Crystallization and preliminary x-ray diffraction studies of ADP-L-glycero-D-mannoheptose 6-epimerase from E-coli K12 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2430 BP A1272 EP A1272 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602918 ER PT J AU Dixon, SC Horti, J Arah, IN Reed, E Figg, WD AF Dixon, SC Horti, J Arah, IN Reed, E Figg, WD TI Optimization of extraction and PCR of DNA from frozen serum SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, DCS, Med Branch, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2082 BP A1213 EP A1213 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602567 ER PT J AU Duensing, TD van Putten, JPM AF Duensing, TD van Putten, JPM TI Polysaccharide mediated interaction of Neisseria gonorrhoeae with Chinese Hamster Ovary cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3414 BP A1440 EP A1440 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603903 ER PT J AU Duhe, RJ DaSilva, L Evans, GA Erwin, RA Kirken, RA Farrar, WL AF Duhe, RJ DaSilva, L Evans, GA Erwin, RA Kirken, RA Farrar, WL TI Two independent mechanisms regulate the catalytic activity of Janus kinases SO FASEB JOURNAL LA English DT Meeting Abstract C1 SAIC, Intramural Res Suopport Program, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Cytokine Mol Mechanisms Sect, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1829 BP A1170 EP A1170 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602314 ER PT J AU Erickson, JW AF Erickson, JW TI Structural mechanisms of drug resistance for HIV-1 protease mutants. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Struct Biochem Program, SAIC, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA A24 BP A856 EP A856 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600485 ER PT J AU Fan, GF Goldsmith, PK Collins, R Dunn, CK Krapcho, KJ Rogers, KV Spiegel, AM AF Fan, GF Goldsmith, PK Collins, R Dunn, CK Krapcho, KJ Rogers, KV Spiegel, AM TI Glycosylation of the human Ca2+-receptor: Characterization and effect on cell surface expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NPS Pharmaceut, Salt Lake City, UT 84103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1784 BP A1162 EP A1162 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602270 ER PT J AU Farshori, PO Kachar, B AF Farshori, PO Kachar, B TI Redistribution and phosphorylation of occludin during tight junction disruption and formation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1921 BP A1186 EP A1186 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602407 ER PT J AU Feinberg, M AF Feinberg, M TI AIDS as a paradigm for understanding the biology of zoonotic diseases SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 855 BP A1003 EP A1003 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601340 ER PT J AU Fu, W Shah, SR Dave, HPG Joshi, JB AF Fu, W Shah, SR Dave, HPG Joshi, JB TI DNA : protein interactions at the HTLV-I tax(1) responsive proximal sequences in the proenkephalin gene promoter SO FASEB JOURNAL LA English DT Meeting Abstract C1 VAMC, Washington, DC USA. NHLBI, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1249 BP A1070 EP A1070 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601733 ER PT J AU Furumura, M Sakai, C Ollmann, M Potterf, SB Vieira, W Barsh, GS Hearing, VJ AF Furumura, M Sakai, C Ollmann, M Potterf, SB Vieira, W Barsh, GS Hearing, VJ TI Novel genes modulated during pheomelanogenesis identified by differential display and subtractive hybridization SO FASEB JOURNAL LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1478 BP A1109 EP A1109 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601965 ER PT J AU Gao, G Al-Toukhi, D Manganiello, VC AF Gao, G Al-Toukhi, D Manganiello, VC TI Cyclic nucleotide phosphodiesterases (PDE) 3 and 4 in peripheral human monocytes and macrophages from peripheral blood SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1501 BP A1113 EP A1113 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601986 ER PT J AU Ge, L Remmers, EF Hansen, C Wilder, RL AF Ge, L Remmers, EF Hansen, C Wilder, RL TI Fine chromosomal mapping of the rat OP (osteopetrotic) gene SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMSD, NIH, Bethesda, MD USA. NIH, Genet Resources Sect, Vet Resources Program, Natl Ctr Res Resources, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 527 BP A947 EP A947 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601014 ER PT J AU Geng, Y Tsai-Morris, CH Buczko, E Dufau, M AF Geng, Y Tsai-Morris, CH Buczko, E Dufau, M TI Expression of the human Luteinizing Hormone Receptor gene: Evidence for multiple promoter activity and gene diversity SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 497 BP A942 EP A942 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600984 ER PT J AU Ghosh, MC Klee, CB AF Ghosh, MC Klee, CB TI Native calcineurin is a Fe2+ enzyme SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 970 BP A1024 EP A1024 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601456 ER PT J AU Glover, CJ Hartman, KD Felsted, RL AF Glover, CJ Hartman, KD Felsted, RL TI Human N-myristoyltransferase N-terminus effects targetting to the ribosomal subcellular fraction SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 628 BP A964 EP A964 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601114 ER PT J AU Goodwin, DC Gunther, MR Hsi, LC Crews, BC Eling, TE Mason, RP Marnett, LJ AF Goodwin, DC Gunther, MR Hsi, LC Crews, BC Eling, TE Mason, RP Marnett, LJ TI Nitric oxide trapping of the Y385 radical during prostaglandin endoperoxide synthase turnover SO FASEB JOURNAL LA English DT Meeting Abstract C1 Vanderbilt Univ, Nashville, TN USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1697 BP A1148 EP A1148 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602185 ER PT J AU Gottesman, S Majdalani, N Sledjeski, D AF Gottesman, S Majdalani, N Sledjeski, D TI Transcriptional and translational control by DSRA, a small RNA SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Microbiol, Toledo, OH 43699 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 75 BP A870 EP A870 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600562 ER PT J AU Grabczyk, E Usdin, K AF Grabczyk, E Usdin, K TI Length dependent transcription attenuation in the Friedreich's ataxia triplet expansion mutation (GAA) via triple helix formation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1998 BP A1199 EP A1199 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602483 ER PT J AU Grobler, JA Hurley, JH AF Grobler, JA Hurley, JH TI Calcium and phospholipid binding to phospholipase C-delta(1): A role for the C2 domain? SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2851 BP A1345 EP A1345 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603339 ER PT J AU Han, JS Kim, HC Chung, JK Kang, HS Donaldson, J Koh, JK AF Han, JS Kim, HC Chung, JK Kang, HS Donaldson, J Koh, JK TI Potential role of Cdc42 protein purified from rat brain cytosol in phospholipase D activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Hanyang Univ, Coll Med, Dept Biochem, Seoul 133791, South Korea. NHLBI, Lab Cell Signalling, Nih, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1769 BP A1160 EP A1160 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602254 ER PT J AU Haque, RM Lee, SJ Jang, JS Chang, LS Trepel, JB AF Haque, RM Lee, SJ Jang, JS Chang, LS Trepel, JB TI Control of the retinoblastoma family of cell-cycle regulatory proteins by an inhibitor of the mevalonate pathway. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2109 BP A1218 EP A1218 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602595 ER PT J AU Helm, BA Sayers, I Machado, DC Padlan, EA AF Helm, BA Sayers, I Machado, DC Padlan, EA TI Applications of rationally designed hIgE-Fc-derived peptides as antagonists of the allergic response. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Sheffield, Dept Mol Biol & Biotechnol, Krebs Inst, Sheffield S10 2UH, S Yorkshire, England. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2723 BP A1323 EP A1323 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603208 ER PT J AU Hinnebusch, A Anderson, J Cuesta, R Garcia-Barrio, M Qiu, H Marton, M Pavitt, G Phan, L Tamame, M de Aldana, CV Yang, W AF Hinnebusch, A Anderson, J Cuesta, R Garcia-Barrio, M Qiu, H Marton, M Pavitt, G Phan, L Tamame, M de Aldana, CV Yang, W TI Translational control of GCN4 by factors controlling initiator tRNA(Met) binding to ribosomes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Bethesda, MD USA. Univ Salamanca, E-37008 Salamanca, Spain. RI Pavitt, Graham/A-1363-2010 OI Pavitt, Graham/0000-0002-8593-2418 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3440 BP A1445 EP A1445 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603931 ER PT J AU Hu, ZZ Zhuang, L Meng, JP Dufau, ML AF Hu, ZZ Zhuang, L Meng, JP Dufau, ML TI Steroidogenic factor-1 is an essential transcriptional activator for gonad-specific expression of promoter I of the rat prolactin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2032 BP A1205 EP A1205 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602518 ER PT J AU Huh, TL Kim, YO Ko, HJ Kim, SH Park, HC Lee, IJ Song, BJ AF Huh, TL Kim, YO Ko, HJ Kim, SH Park, HC Lee, IJ Song, BJ TI Human mitochondrial NAD(+)-specific isocitrate dehydrogenase beta and gamma subunits: Cloning, tissue specific expression, and functional analyses of the recombinant proteins. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Kyungpook Natl Univ, Dept Genet Engn, Taegu 702701, South Korea. NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 199 BP A892 EP A892 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600685 ER PT J AU Ibeanu, GC Rettie, AE Haining, RL Ghanayem, BI Goldstein, JA AF Ibeanu, GC Rettie, AE Haining, RL Ghanayem, BI Goldstein, JA TI Structural determinants of regiospecificity of human CYP2C19 for R-warfarin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P135 BP A794 EP A794 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600137 ER PT J AU Ishaq, M Fan, M Natarajan, V AF Ishaq, M Fan, M Natarajan, V TI Activation-induced down-regulation of RXR alpha expression in human T cells - A possible role in cell cycle SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1237 BP A1068 EP A1068 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601721 ER PT J AU Islam, MN Jones, CS Chiantore, MV Andreola, F De Luca, M AF Islam, MN Jones, CS Chiantore, MV Andreola, F De Luca, M TI Liarozole potentiates retinoic acid effects on human prostate carcinoma cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2327 BP A1255 EP A1255 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602814 ER PT J AU Iyer, V DeRisi, J Eisen, M Ross, D Spellman, P Hudson, J Schuler, G Lashkari, D Shalon, D Botstein, D Brown, P AF Iyer, V DeRisi, J Eisen, M Ross, D Spellman, P Hudson, J Schuler, G Lashkari, D Shalon, D Botstein, D Brown, P TI Use of DNA microarrays to monitor differential gene expression in yeast and humans. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Res Genet Inc, Huntsville, AL 35801 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Synteni Inc, Fremont, CA USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1571 BP A1126 EP A1126 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602056 ER PT J AU Jhon, DY Rhee, SG AF Jhon, DY Rhee, SG TI Identification of multiple residues in PLC-beta 1 phosphorylated by PKC SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2873 BP A1348 EP A1348 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603359 ER PT J AU Jin, HM Kikly, K Qiu, XY Kirkpatrick, RB Abdel-Meguid, SS Copeland, NG Rosenberg, M AF Jin, HM Kikly, K Qiu, XY Kirkpatrick, RB Abdel-Meguid, SS Copeland, NG Rosenberg, M TI Molecular characterization of YM-1, a chitinase-related gene expressed in mouse hematopoietic cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 SmithKline Beecham Pharmaceut, R&D, King Of Prussia, PA 19406 USA. Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2091 BP A1214 EP A1214 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602577 ER PT J AU Khan, AR Chernaia, MM Tarasova, NI James, MNG AF Khan, AR Chernaia, MM Tarasova, NI James, MNG TI Structure of folding intermediate during activation of an aspartic proteinase zymogen SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alberta, Edmonton, AB, Canada. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3162 BP A1397 EP A1397 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603648 ER PT J AU Kim, JR Lee, C Kang, HS Chung, JK Sekiya, F Han, JS Kim, SR Bae, YS Morris, AJ Rhee, SG AF Kim, JR Lee, C Kang, HS Chung, JK Sekiya, F Han, JS Kim, SR Bae, YS Morris, AJ Rhee, SG TI Inhibition of phospholipase D by clathrin assembly protein 3 (AP3) SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. RI Morris, Andrew/B-7869-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2865 BP A1347 EP A1347 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603352 ER PT J AU Kim, SY Bae, CD Choi, EY Marekov, LN Steinert, PM AF Kim, SY Bae, CD Choi, EY Marekov, LN Steinert, PM TI The expression of transglutaminase 1 in normal neurons and fibroblasts SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 148 BP A883 EP A883 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600635 ER PT J AU Klee, CB Wang, XT AF Klee, CB Wang, XT TI Calcineurin: Coupling between oxidative stress and calcium signaling. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Biochem Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1542 BP A1120 EP A1120 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602028 ER PT J AU Klose, TS Ghanayem, BI Goldstein, JA AF Klose, TS Ghanayem, BI Goldstein, JA TI Determination of active sites of metabolism for diclofenac by human CYP2C chimeras in a bacterial expression system SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P136 BP A794 EP A794 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600135 ER PT J AU Kostenis, E Degtyarev, M Conklin, B Wess, J AF Kostenis, E Degtyarev, M Conklin, B Wess, J TI Importance of the amino terminal extension of G alpha q in receptor/G-protein coupling specificity SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1137 BP A1052 EP A1052 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601623 ER PT J AU Kresse, H Schonherr, E O'Connell, B Fisher, LW Young, M Schittny, J Vischer, P AF Kresse, H Schonherr, E O'Connell, B Fisher, LW Young, M Schittny, J Vischer, P TI Expression of decorin in endothelial cells undergoing angiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Munster, Inst Physiol Chem & Pathobiochem, D-4400 Munster, Germany. NIDR, NIH, Bethesda, MD 20892 USA. Univ Bern, Inst Anat, Bern, Switzerland. Univ Munster, Inst Arteriosclerosis Res, D-4400 Munster, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2535 BP A1291 EP A1291 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603024 ER PT J AU Kundu, GC Mukherjee, AB AF Kundu, GC Mukherjee, AB TI Human uteroglobin receptors(s) in normal and cancer cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Sect Dev Genet, HDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1152 BP A1054 EP A1054 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601639 ER PT J AU Lavandero, S Perez, V Foncea, R Sapag-Hagar, M LeRoith, D AF Lavandero, S Perez, V Foncea, R Sapag-Hagar, M LeRoith, D TI IGF-I activates polyphosphoinositide hydrolysis, protein kinase C isoforms and ERK pathway in cultured neonatal rat cardiac myocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Chile, Santiago, Chile. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 352 BP A917 EP A917 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600839 ER PT J AU Le, Y Gagneten, S Larson, T Miller, J Sauer, B AF Le, Y Gagneten, S Larson, T Miller, J Sauer, B TI Brief expression of a GFPcre fusion gene in embryonic stem cells allows rapid retrieval of site-specific genomic deletions SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKD, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1985 BP A1197 EP A1197 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602471 ER PT J AU Lee, BJ Chittum, HS Baek, HJ Park, SI Yang, ES Gladyshev, VN Park, JM Moustafa, ME Carlson, BA Diamond, AM Hatfield, DL AF Lee, BJ Chittum, HS Baek, HJ Park, SI Yang, ES Gladyshev, VN Park, JM Moustafa, ME Carlson, BA Diamond, AM Hatfield, DL TI Role of selenocysteine (Sec) tRNA([SER]SEC) in selenoprotein biosynthesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 SNU, IMBG, LMG, Seoul, South Korea. NCI, LBR, DBS, NIH, Bethesda, MD 20892 USA. Univ Chicago, DRCO, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2199 BP A1233 EP A1233 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602685 ER PT J AU Lee, M Anderson, WB AF Lee, M Anderson, WB TI Activation or Raf-1 protein kinase by hydrogen peroxide treatment of cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1920 BP A1185 EP A1185 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602406 ER PT J AU Lee, SH Yajima, S Mouradian, MM AF Lee, SH Yajima, S Mouradian, MM TI Sp family transcription factors regulate the rat D2 dopamine receptor gene SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3046 BP A1378 EP A1378 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603538 ER PT J AU Lee, SR Kwon, KS Wu, YL Rhee, SG AF Lee, SR Kwon, KS Wu, YL Rhee, SG TI Reversible inactivation of protein tyrosine phosphatase 1B by hydrogen peroxide generated in A431 cells stimulated with epidermal growth factor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2921 BP A1356 EP A1356 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603407 ER PT J AU Lesma, E Moss, J Brewer, HB Bortell, R Greiner, D Mordes, J Rossini, A AF Lesma, E Moss, J Brewer, HB Bortell, R Greiner, D Mordes, J Rossini, A TI Injection of anti-RT6.1 antibodies into diabetes-resistant rats increases plasma RT6 alloantigen. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Pulm & Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Med Ctr, Diabet Div, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 623 BP A963 EP A963 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601111 ER PT J AU Li, Q Bruton, F Reed, E AF Li, Q Bruton, F Reed, E TI Regulation of ERCC1 mRNA expression in human ovarian cancer cells in response to pharmacologic agents. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1248 BP A1070 EP A1070 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601735 ER PT J AU Li, YL Grivel, JC Viswanathan, M Smith-Gill, SJ AF Li, YL Grivel, JC Viswanathan, M Smith-Gill, SJ TI High-resolution epitope mapping of Hen Egg Lysozyme mAbs by alanine-scanning mutagenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1087 BP A1043 EP A1043 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601574 ER PT J AU Liu, YS Pineyro, MA Wang, XY Martindale, JL Holbrook, NJ AF Liu, YS Pineyro, MA Wang, XY Martindale, JL Holbrook, NJ TI Arsenite activates ERK MAP kinase and enhances interaction between Grb2 and Shc SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA, Biol Chem Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2943 BP A1360 EP A1360 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603430 ER PT J AU Lorenzi, MV Castagnino, P Chen, QO Chedid, M Miki, T AF Lorenzi, MV Castagnino, P Chen, QO Chedid, M Miki, T TI Ligand independent activation of fibroblast growth factor receptor-2 by carboxyl terminal alterations SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2770 BP A1331 EP A1331 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603255 ER PT J AU Luo, G Blaisdell, J Hodgson, E Goldstein, JA AF Luo, G Blaisdell, J Hodgson, E Goldstein, JA TI Cloning of mouse CYP2C subfamily SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P310 BP A824 EP A824 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600310 ER PT J AU Lyakh, L Ghosh, P Rice, NR AF Lyakh, L Ghosh, P Rice, NR TI Expression of NFAT-family proteins in normal human T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 SAIC, ABL Basic Res Program, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 475 BP A938 EP A938 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600961 ER PT J AU Ma, J Fiedorek, JT Ramachandran, S Zeldin, DC AF Ma, J Fiedorek, JT Ramachandran, S Zeldin, DC TI Cloning, expression and chromosomal localization of mouse CYP2J5 and CYP2J6. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC 27515 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P204 BP A806 EP A806 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600204 ER PT J AU Makar, TK Accili, D Giovanni, G Milstien, S AF Makar, TK Accili, D Giovanni, G Milstien, S TI Nitric oxide-mediated apoptosis in astrocytes from insulin receptor knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, LCMR, Bethesda, MD USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3388 BP A1436 EP A1436 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603880 ER PT J AU Marsh, JW Schrager, JA Nunn, MF AF Marsh, JW Schrager, JA Nunn, MF TI HIV Nef lowers threshold for T cell activation and associates with a serine kinase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 738 BP A982 EP A982 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601225 ER PT J AU Marshall, AD McPhie, P Jakoby, WB AF Marshall, AD McPhie, P Jakoby, WB TI Alteration of activity and substrate specificity of aryl sulfotransferase IV upon cysteine oxidation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1641 BP A1138 EP A1138 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602127 ER PT J AU Meacci, E Vasta, V Moorman, JP Hahn, C Bobak, D Bruni, P Moss, J Vaughan, M AF Meacci, E Vasta, V Moorman, JP Hahn, C Bobak, D Bruni, P Moss, J Vaughan, M TI Effect of inhibition of Rho and ADP-ribosylation factor (ARF) activities on phorbol myristate acetate (PMA)-stimulated phospholipase D activity in human adenocarcinoma A549 cells and human primary bronchial epithelial cells (HBEC). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Univ Florence, Dept Biochem Sci, Florence, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2219 BP A1236 EP A1236 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602704 ER PT J AU Moskovitz, J Berlett, BS Poston, JM Stadtman, ER AF Moskovitz, J Berlett, BS Poston, JM Stadtman, ER TI Antioxidant activity of methionine sulfoxide reductase (MSRA) in yeast cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 939 BP A1018 EP A1018 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601425 ER PT J AU Nagababu, E Balagopalakrishna, C Rifkind, JM AF Nagababu, E Balagopalakrishna, C Rifkind, JM TI Hydrogen peroxide produced during autoxidation associated with heme degradation SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, NIA, LCMB, Mol Dynam Sect, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 775 BP A989 EP A989 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601264 ER PT J AU Nagaich, AK Appella, E Harrington, RE AF Nagaich, AK Appella, E Harrington, RE TI DNA bending is essential for the site specific recognition by DNA binding domain of tumor suppressor protein p53 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Nevada, Dept Biochem 330, Reno, NV 89557 USA. NCI, Cell Biol Lab, NIDDK, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3343 BP A1428 EP A1428 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603832 ER PT J AU Nair, RMG Pennill, L Singh, D Thomas, P AF Nair, RMG Pennill, L Singh, D Thomas, P TI Studies on the combined biological activity of cytotoxic & hormonal drugs on breast tumors in animal models. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Savannah State Univ, Coll Sci & Technol, Savannah, GA USA. Meharry Med Sch, Nashville, TN USA. NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2305 BP A1251 EP A1251 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602791 ER PT J AU Negishi, M Sueyoshi, T AF Negishi, M Sueyoshi, T TI Using Peptitergent to engineer microsomal P450 to soluble enzyme. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Pharmacogenet Sect, LRDT, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P67 BP A782 EP A782 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600069 ER PT J AU Normant, E Loh, YP AF Normant, E Loh, YP TI Carboxypeptidase E acts as a sorting receptor for routing proinsulin and proenkephalin but not chromogranin A to the regulated secretory pathway SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Cellular Neurobiol Sect, LDN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 431 BP A931 EP A931 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600918 ER PT J AU Nosworthy, NJ Seok, YJ Peterkofsky, A Ginsburg, A AF Nosworthy, NJ Seok, YJ Peterkofsky, A Ginsburg, A TI E-coli phosphotransferase (PTS) enzyme I amino terminal domain stability SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 286 BP A906 EP A906 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600771 ER PT J AU Ooi, GT Hurst, KR Poy, MN Rechler, MM Boisclair, YR AF Ooi, GT Hurst, KR Poy, MN Rechler, MM Boisclair, YR TI Growth hormone stimulation of the acid-labile subunit (ALS) gene expression in rat liver cells is mediated by STAT5a and -5b isoforms. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3074 BP A1382 EP A1382 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603557 ER PT J AU Osheroff, WP Beard, WA Prasad, R Wilson, SH Kunkel, TA AF Osheroff, WP Beard, WA Prasad, R Wilson, SH Kunkel, TA TI Alteration of an active site contact is human DNA polymerase beta results in a frameshift mutator polymerase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1965 BP A1193 EP A1193 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602452 ER PT J AU Park, JM Hatfield, DL Lee, BJ AF Park, JM Hatfield, DL Lee, BJ TI Purification and characterization of Xenopus transcription factor IIIB SO FASEB JOURNAL LA English DT Meeting Abstract C1 Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2059 BP A1209 EP A1209 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602546 ER PT J AU Patel, BKR Pierce, JH LaRochelle, WJ AF Patel, BKR Pierce, JH LaRochelle, WJ TI Regulation of IL-4-mediated signalling by the naturally occurring dominant negative and attenuated forms of human Stat6 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1824 BP A1169 EP A1169 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602311 ER PT J AU Paul, WE AF Paul, WE TI Prospects for immunologic control of HIV infection SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Off AIDS Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 853 BP A1003 EP A1003 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601339 ER PT J AU Pena, MSR Woodard, C Collins, R Spiegel, A AF Pena, MSR Woodard, C Collins, R Spiegel, A TI Decreased insulin content and secretion in RIN 1046-38 cells overexpressing alpha 2a-adrenergic SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, MDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1783 BP A1162 EP A1162 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602267 ER PT J AU Pham, PT McHenry, CS Schaaper, RM AF Pham, PT McHenry, CS Schaaper, RM TI The in vitro fidelity of E-coli DNA polymerase III holoenzyme from wild-type and mutD5 strains SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2991 BP A1368 EP A1368 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603474 ER PT J AU Poirot, S Gigoux, V Escrieut, C Maigret, B Vaysse, N Wank, S Fourmy, D AF Poirot, S Gigoux, V Escrieut, C Maigret, B Vaysse, N Wank, S Fourmy, D TI Mapping of the agonist binding sites of the CCK-A and CCK-B/gastrin receptors SO FASEB JOURNAL LA English DT Meeting Abstract C1 CHU Rangueil, IFR L Bugnard, INSERM U151, F-31403 Toulouse, France. CNRS UA 510, Nancy, France. NIDDK, NIH, Bethesda, MD USA. RI Poirot, Sandrine/D-5448-2017 NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1762 BP A1159 EP A1159 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602250 ER PT J AU Qu, W Fiedorek, FT Zeldin, DC AF Qu, W Fiedorek, FT Zeldin, DC TI Nutritional status modulates rat liver p450 arachidonic acid metabolism. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P202 BP A806 EP A806 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600203 ER PT J AU Ray, K Fan, GF Goldsmith, PK Spiegel, AM AF Ray, K Fan, GF Goldsmith, PK Spiegel, AM TI Mutational analysis of the carboxyl-terminal region of the human calcium-sensing receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1823 BP A1169 EP A1169 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602308 ER PT J AU Raymond, G Hope, J Kocisko, D Priola, S Raymond, L Bossers, A Lansbury, P Caughey, B AF Raymond, G Hope, J Kocisko, D Priola, S Raymond, L Bossers, A Lansbury, P Caughey, B TI Molecular assessment of human susceptibility to BSE and scrapie SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT USA. MIT, Cambridge, MA 02139 USA. DLO, Lelystad, Netherlands. RI Hope, James/C-4966-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3419 BP A1441 EP A1441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603905 ER PT J AU Rebois, RV Basi, NS AF Rebois, RV Basi, NS TI Gpp[NH]p binding to G delta in solution causes large conformational changes in the heterotrimer but not subunit dissociation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1120 BP A1049 EP A1049 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601608 ER PT J AU Richter-Cook, NJ Dever, TE Merrick, WC AF Richter-Cook, NJ Dever, TE Merrick, WC TI Purification and characterization of a new eukaryotic translation factor: Eukaryotic translation factor 4H. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3195 BP A1403 EP A1403 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603687 ER PT J AU Rubin, I He, X Kelley, M Uren, A Schaudies, P Popescu, N Rudikoff, S Aaronson, S Varmus, H Finch, P AF Rubin, I He, X Kelley, M Uren, A Schaudies, P Popescu, N Rudikoff, S Aaronson, S Varmus, H Finch, P TI Purification and molecular cloning of a secreted, frizzled-related Wnt antagonist SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1483 BP A1110 EP A1110 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601968 ER PT J AU Sakata, H Stahl, SJ Taylor, WG Rosenberg, JM Sakaguchi, K Wingfield, PT Rubin, JS AF Sakata, H Stahl, SJ Taylor, WG Rosenberg, JM Sakaguchi, K Wingfield, PT Rubin, JS TI Heparin-binding and oligomerization of hepatocyte growth factor/scatter factor isoforms; Heparan sulfate glycosaminoglycan requirement for Met binding and signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 391 BP A924 EP A924 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600877 ER PT J AU Sauer, RT Roche, E Gottesman, S AF Sauer, RT Roche, E Gottesman, S TI Targeted degradation of bacterial proteins SO FASEB JOURNAL LA English DT Meeting Abstract C1 MIT, Dept Biol, Cambridge, MA USA. NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 17 BP A860 EP A860 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600503 ER PT J AU Sayers, I Machado, DC Cain, SA Pickett, M Padlan, EA Helm, BA AF Sayers, I Machado, DC Cain, SA Pickett, M Padlan, EA Helm, BA TI A kinetic analysis of the IgE-Fc epsilon RI alpha interaction using surface plasmon resonance. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Sheffield, Krebs Inst, MBB, Sheffield S10 2UH, S Yorkshire, England. Univ Southampton, Dept Mol Microbiol, Southampton, Hants, England. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2952 BP A1362 EP A1362 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603444 ER PT J AU Schedin, S Sindelar, P Pentchev, P Dallner, G AF Schedin, S Sindelar, P Pentchev, P Dallner, G TI Peroxisomal defects associated with Niemann-Pick type C disease SO FASEB JOURNAL LA English DT Meeting Abstract C1 Stockholm Univ, S-10691 Stockholm, Sweden. Karolinska Inst, Stockholm, Sweden. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3371 BP A1433 EP A1433 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603863 ER PT J AU Sekiya, F Kim, JR Chung, JK Kang, HS Lee, C Kim, SR Bae, YS Morris, AJ Rhee, SG AF Sekiya, F Kim, JR Chung, JK Kang, HS Lee, C Kim, SR Bae, YS Morris, AJ Rhee, SG TI Synaptojanin inhibition of phospholipase D activity by hydrolysis of phosphatidylinositol 4,5-bisphosphate. SO FASEB JOURNAL LA English DT Meeting Abstract C1 SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RI Morris, Andrew/B-7869-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2869 BP A1348 EP A1348 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603357 ER PT J AU Shakur, Y Manganiello, VC AF Shakur, Y Manganiello, VC TI Membrane targeting of cyclic nucleotide phosphodiesterase (PDE3). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1209 BP A1064 EP A1064 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601695 ER PT J AU Sharma, M Pant, HC AF Sharma, M Pant, HC TI Regulation of phosphorylation of neurofilaments in SHSY5Y neuroblastoma cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Lab Neurobiol & Neurochem, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1914 BP A1184 EP A1184 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602400 ER PT J AU Sharma, P Barchi, JJ Huang, X Amin, ND Albers, RW Pearlstein, R Pant, HC AF Sharma, P Barchi, JJ Huang, X Amin, ND Albers, RW Pearlstein, R Pant, HC TI Phosphorylation of neurofilament proteins by neuronal cyclin dependent kinase-5: Structural basis SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neurochem Lab, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, Bethesda, MD 20892 USA. NIH, Struct Biol Lab, Dept Comp Res & Training, Bethesda, MD 20892 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1913 BP A1184 EP A1184 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602397 ER PT J AU Shears, S AF Shears, S TI Versatility of inositol phosphate signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2570 BP A1297 EP A1297 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603057 ER PT J AU Shen, TJ Ikonomi, P Noguchi, CT Ho, C AF Shen, TJ Ikonomi, P Noguchi, CT Ho, C TI Multiribozyme suppression of human alpha-globin gene expression in K562 cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. RI Ho, Chien/O-6112-2016 OI Ho, Chien/0000-0002-4094-9232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 3218 BP A1407 EP A1407 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603710 ER PT J AU Soh, Y Kallarakal, AT Jeng, J Song, BJ AF Soh, Y Kallarakal, AT Jeng, J Song, BJ TI Critical role of the Arg(433) residue in rat transketolase as probed by site-directed mutagenesis and molecular modeling SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 980 BP A1025 EP A1025 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601464 ER PT J AU Soh, Y Kim, MK Seidel, J Green, MV Carrasquiloo, JA Paik, CH Song, BJ AF Soh, Y Kim, MK Seidel, J Green, MV Carrasquiloo, JA Paik, CH Song, BJ TI Protective effect of a CYP2E1 inhibitor, YH439, on CCl4-induced acute hepatitis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, Bethesda, MD USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P309 BP A824 EP A824 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600312 ER PT J AU Swann, PG Song, S Szallasi, Z Blumberg, PM Rivera, J AF Swann, PG Song, S Szallasi, Z Blumberg, PM Rivera, J TI Association of PKC delta with Src kinase family members in the RBL-2H3 mucosal mast cell line: Implications on the regulation of Src and Lyn activity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2930 BP A1358 EP A1358 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603415 ER PT J AU Szweda, PA Tsaiy, L Szweda, LI AF Szweda, PA Tsaiy, L Szweda, LI TI Chemical characterization of a fluorescent 4-hydroxy-2-nonenal-derived protein cross-link: Detection in biological samples SO FASEB JOURNAL LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2374 BP A1263 EP A1263 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602861 ER PT J AU Takenaka, T Hendrickson, CS Tudor, M Schiffmann, R Brady, RO Medin, JA AF Takenaka, T Hendrickson, CS Tudor, M Schiffmann, R Brady, RO Medin, JA TI Extending metabolic cooperativity in gene transfer for Fabry disease: Transduction of patient bone marrow cells leads to intracellular enzymatic correction and secretion. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, DMNB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1364 BP A1090 EP A1090 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601852 ER PT J AU Tang, PZ Tsai-Morris, CH Hu, ZZ Dufau, ML AF Tang, PZ Tsai-Morris, CH Hu, ZZ Dufau, ML TI Differential regulation of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in gonadotropin-induced steroidogenic desensitization of gonadal cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Sect Mol Endocrinol, ERRB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 950 BP A1020 EP A1020 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601434 ER PT J AU Tomassetti, A Mangiarotti, F Mazzi, M Colnaghi, MI Miotti, S Nachmanoff, K Canevari, S Elwood, PC AF Tomassetti, A Mangiarotti, F Mazzi, M Colnaghi, MI Miotti, S Nachmanoff, K Canevari, S Elwood, PC TI Transcriptional regulation of the human alpha folate receptor: Functional analysis of the P1 and P4 promoters in ovarian carcinoma cell lines. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Ist Nazl Tumori, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 456 BP A935 EP A935 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600945 ER PT J AU Valdez, A Roche, P AF Valdez, A Roche, P TI Identification of a novel syntaxin-like protein present in multiple tissues SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1203 BP A1063 EP A1063 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601689 ER PT J AU Venkatachalam, KV Akita, H Strott, CA AF Venkatachalam, KV Akita, H Strott, CA TI Molecular cloning, expression and characterization of human bifunctional PAPS synthase and its functional domains SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Sect Steroid Regulat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1007 BP A1030 EP A1030 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601495 ER PT J AU Walker, H Ferretti, J Stadtman, TC AF Walker, H Ferretti, J Stadtman, TC TI Mechanistic studies of E-coli selenophosphate synthetase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1708 BP A1150 EP A1150 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602194 ER PT J AU Walker, SL Wonderling, RS Owens, RA AF Walker, SL Wonderling, RS Owens, RA TI Identification of critical residues in the adeno-associated virus Rep68 protein necessary for site-specific endonuclease activity SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, IMCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1973 BP A1194 EP A1194 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602459 ER PT J AU Wang, QJ Acs, P Goodnight, J Blumberg, PM Mischak, H Mushinski, JF AF Wang, QJ Acs, P Goodnight, J Blumberg, PM Mischak, H Mushinski, JF TI The catalytic domain of PKC-epsilon in reciprocal PKC-delta and -epsilon chimeras contains the major determinants for cell transformation and tumorigenicity in NIH 3T3 cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Mischak, Harald/E-8685-2011; Wang, Qiming/B-6064-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1933 BP A1188 EP A1188 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602419 ER PT J AU Wess, J Gomeza, J Kostenis, E AF Wess, J Gomeza, J Kostenis, E TI Structural analysis of receptor/G-protein coupling specificity SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1136 BP A1051 EP A1051 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601622 ER PT J AU Wibbenmeyer, JA Wagner, RA Xavier, KA Smith-Gill, SJ Willson, RC AF Wibbenmeyer, JA Wagner, RA Xavier, KA Smith-Gill, SJ Willson, RC TI Testing the structural basis of lysozyme recognition by antibody HyHEL-5. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Houston, Dept Chem Engn, Houston, TX 77204 USA. Univ Houston, Dept Biochem & Biophys Sci, Houston, TX 77204 USA. NCI, NIH, Bethesda, MD 20995 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA M22 BP A834 EP A834 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600369 ER PT J AU Witteveen, CFB Giovanelli, J Yim, MB Kaufman, S AF Witteveen, CFB Giovanelli, J Yim, MB Kaufman, S TI The first half reaction of nitric oxide synthase: The conversion of arginine to N-hydroxyarginine. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Neurochem Lab, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1028 BP A1033 EP A1033 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601512 ER PT J AU Wolff, EC Joe, YA Lee, YB Folk, JE Park, MH AF Wolff, EC Joe, YA Lee, YB Folk, JE Park, MH TI Identification of an active site residue in deoxyhypusine synthase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1645 BP A1139 EP A1139 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602132 ER PT J AU Wu, JO Ozarowski, A Maki, AH Urbaneja, MA Henderson, LE Casas-Finet, JR AF Wu, JO Ozarowski, A Maki, AH Urbaneja, MA Henderson, LE Casas-Finet, JR TI Phosphorescence & optical detection of magnetic resonance (ODMR) study of nucleic acid binding of HIV-1 NC protein (P7) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif Davis, Dept Chem, Livermore, CA 95616 USA. NCI, Frederick Canc Res & Dev Ctr, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2415 BP A1270 EP A1270 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602902 ER PT J AU Wu, YL Rhee, SG AF Wu, YL Rhee, SG TI Probing cellular protein target(s) of oxidant signaling and oxidative damage with fluorescent labeled thiol-specific reagents SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Lab Cell Signalling, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 1135 BP A1051 EP A1051 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601619 ER PT J AU Yang, TJ Krausz, KW Shou, MG Gonzalez, FJ Gelboin, HV AF Yang, TJ Krausz, KW Shou, MG Gonzalez, FJ Gelboin, HV TI A monoclonal antibody (MAb) inhibitory to human P450 2D6: A paradigm for determining an individual P450s role in the tissue metabolism of specific drugs SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA P321 BP A826 EP A826 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600324 ER PT J AU Yang, YL Jakoby, WB AF Yang, YL Jakoby, WB TI Purification and identification of a rat liver ethylene carbonate-hydrolyzing enzyme as an imidase SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 207 BP A893 EP A893 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305600692 ER PT J AU Yim, MB Kang, JH Yim, HS Chock, PB Stadtman, ER AF Yim, MB Kang, JH Yim, HS Chock, PB Stadtman, ER TI Enhanced free radical-generating function of Cu,Zn-SOD FALS mutants: Clinical severity and the K-m value. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 985 BP A1026 EP A1026 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305601472 ER PT J AU Yoon, HW Bae, YS Rhee, SG AF Yoon, HW Bae, YS Rhee, SG TI Mechanism by which hydrogen peroxide enhances intracellular calcium in A431 cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, LCS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2922 BP A1357 EP A1357 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603414 ER PT J AU Yuan, CJ Zhang, ZJ Mukherjee, AB AF Yuan, CJ Zhang, ZJ Mukherjee, AB TI Transcriptional regulation of mouse cyclooxygenase-2 gene by group-I phospholipase A2 in MC3T3 cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2024 BP A1203 EP A1203 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602508 ER PT J AU Zdanovsky, AG FitzGerald, DJ AF Zdanovsky, AG FitzGerald, DJ TI Region of Pseudomonas exotoxin a surrounding Trp(281) is important for the toxicity of exotoxin A-derived immunotoxins. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Promega, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2736 BP A1325 EP A1325 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305603223 ER PT J AU Zhou, XY Ding, L Coleman, WG AF Zhou, XY Ding, L Coleman, WG TI Glycine 6 is a functionally important residue in ADP-L-glycero-D-mannoheptose 6-epimerase from Escherichia coli. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, Biochem Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL 31 PY 1997 VL 11 IS 9 SU S MA 2432 BP A1272 EP A1272 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ZK302 UT WOS:000073305602919 ER PT J AU Varmus, H AF Varmus, H TI US support for malaria research SO NATURE LA English DT Letter RP Varmus, H (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 31 PY 1997 VL 388 IS 6641 BP 416 EP 416 DI 10.1038/41193 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XN553 UT WOS:A1997XN55300014 PM 9242391 ER PT J AU Ramsden, DA Paull, TT Gellert, M AF Ramsden, DA Paull, TT Gellert, M TI Cell-free V(D)J recombination SO NATURE LA English DT Article ID DNA-LIGASE-I; MOUSE THYMOCYTES; MAMMALIAN-CELLS; REARRANGEMENT; REPAIR AB V(D)J recombination generates diversity in the immune system through the lymphoid-specific assembly of multiple gene segments into functional immunoglobulin and T-cell receptor genes (for reviews, see refs 1, 2). The first step in V(D)J recombination is cleavage of DNA at recombination signal sequences. Cleavage produces a blunt DNA end on each signal sequence and a hairpin end on adjacent coding gene segments(3,4), and can be reproduced in vitro by using purified RAG1 and RAG2 proteins(5,6). The later steps involve processing and joining of the cleaved DNA ends, and until now have been studied only in cells, Here we reconstitute the complete V(D)J recombination reaction in a cell-free system, We find that the RAG proteins are not only involved in cleavage, but are also needed in the later steps for efficient joining of coding ends. Joining is largely directed by short pieces of identical sequence in the coding flanks, but addition of human DNA ligase I results in greater diversity. Coding junctions contain short deletions as well as additions complementary to a coding flank (P nucleotides). Addition of non-templated nucleotides into coding junctions is mediated by terminal deoxyribonucleotidyl transferase. The cell-free reaction can therefore reproduce the complete set of processing events that occur in cells. C1 NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 22 TC 107 Z9 108 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 JUL 31 PY 1997 VL 388 IS 6641 BP 488 EP 491 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XN553 UT WOS:A1997XN55300052 PM 9242409 ER PT J AU Gordin, FM Matts, JP Miller, C Brown, LS Hafner, R John, SL Klein, M Vaughn, A Besch, CL Perez, G Szabo, S ElSadr, W AF Gordin, FM Matts, JP Miller, C Brown, LS Hafner, R John, SL Klein, M Vaughn, A Besch, CL Perez, G Szabo, S ElSadr, W TI A controlled trial of isoniazid in persons with anergy and human immunodeficiency virus infection who are at high risk for tuberculosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NEW-YORK-CITY; ACTIVE TUBERCULOSIS; DRUG-USERS; HIV; EPIDEMIOLOGY; PROGRESSION; OUTBREAK AB Background Patients with human immunodeficiency virus (HIV) infection and latent tuberculosis are at substantial risk for the development of active tuberculosis. As a public health measure, prophylactic treatment with isoniazid has been suggested for HIV-infected persons who have anergy and are in groups with a high prevalence of tuberculosis. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled trial of six months of prophylactic isoniazid treatment in HIV-infected patients with anergy who have risk factors for tuberculosis infection. The primary end point was culture-confirmed tuberculosis. Results The study was conducted from November 1991 through June 1996. Over 90 percent of the patients had two or more risk factors for tuberculosis infection, and nearly 75 percent of patients were from greater New York City. After a mean follow-up of 33 months, tuberculosis was diagnosed in only 6 of 257 patients in the placebo group and 3 of 260 patients in the isoniazid group (risk ratio, 0.48; 95 percent confidence interval, 0.12 to 1.91; P=0.30). There were no significant differences between the two groups with regard to death, the progression of HIV disease or death, or adverse events. Conclusions Even in HIV-infected patients with anergy and multiple risk factors for latent tuberculosis infection, the rate of development of active tuberculosis is low. This finding does not support the use of isoniazid prophylaxis in high-risk patients with HIV infection and anergy unless they have been exposed to active tuberculosis. (C) 1997, Massachusetts Medical Society. C1 GEORGETOWN UNIV,WASHINGTON,DC. UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,COMMUNITY PROGRAMS CLIN RES AIDS STAT CTR,MINNEAPOLIS,MN 55455. ADDICT RES TREATMENT CORP,NEW YORK,NY. COLUMBIA UNIV,NEW YORK,NY. NIAID,DIV AIDS,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,HARLEM HOSP CTR,DIV INFECT DIS,NEW YORK,NY 10032. CLIN DIRECTORS NETWORK REG 2 INC,NEW YORK,NY. TULANE UNIV,MED CTR,NEW ORLEANS,LA. NEW JERSEY COMMUNITY RES INITIAT,NEWARK,NJ. DELAWARE COMMUNITY PROGRAM CLIN RES AIDS,WILMINGTON,DE. RP Gordin, FM (reprint author), VET AFFAIRS MED CTR,INFECT DIS SECT 151B,MED SERV,50 IRVING ST NW,WASHINGTON,DC 20422, USA. NR 29 TC 127 Z9 129 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 31 PY 1997 VL 337 IS 5 BP 315 EP 320 DI 10.1056/NEJM199707313370505 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA XN119 UT WOS:A1997XN11900005 PM 9233868 ER PT J AU Curtis, RE Rowlings, PA Deeg, HJ AF Curtis, RE Rowlings, PA Deeg, HJ TI Solid cancers after bone marrow transplantation - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CHILDHOOD; NEOPLASMS C1 MED COLL WISCONSIN,MILWAUKEE,WI 53226. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP Curtis, RE (reprint author), NCI,BETHESDA,MD 20852, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 31 PY 1997 VL 337 IS 5 BP 346 EP 346 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XN119 UT WOS:A1997XN11900018 ER PT J AU Alimandi, M Heidaran, MA Gutkind, JS Zhang, JC Ellmore, N Valius, M Kazlauskas, A Pierce, JH Li, WQ AF Alimandi, M Heidaran, MA Gutkind, JS Zhang, JC Ellmore, N Valius, M Kazlauskas, A Pierce, JH Li, WQ TI PLC-gamma activation is required for PDGF-beta R-mediated mitogenesis and monocytic differentiation of myeloid progenitor cells SO ONCOGENE LA English DT Article DE PLC-gamma; PDGF-beta R; monocytic differentiation ID PROTEIN-KINASE-C; GROWTH-FACTOR; PHOSPHOLIPASE-C; MONOCLONAL-ANTIBODY; RECEPTOR; DELTA; ALPHA; AUTOPHOSPHORYLATION; PHOSPHORYLATION; INVOLVEMENT AB To investigate the molecular mechanisms mediating hematopoietic cell differentiation and mitogenesis by activation of the platelet-derived growth factor beta receptor (PDGF-beta R), the mild type PDGF-beta R (PDGF-beta RWT) and tyrosine to phenylalanine mutants of the PDGF-beta R, including F751, F966, F970, F1009, F1021 and F1009/F1021 were overexpressed in FDC-P2 myeloid progenitor cells by retroviral-mediated gene transfer. Stimulation of PDGF-beta RWT and F966, F970 and F1009 infectants with PDGF-BB led to the increased expression of monocytic differentiation markers, In contrast, activation of PDGF-beta R in the parental line or the F1021 or F1009/F1021 mutant infectants failed to induce monocytic differentiation, PDGF-BB stimulation of PDGF-beta RWT, F751, F966, F970 and F1009 infectants led to pronounced DNA synthesis, whereas F1021 and F1009/F1021 infectants did not reveal any increase in mitogenesis when compared to that of the FDC-P2 line, While PDGF stimulation of FDC-2 cells overexpressing PDGF-beta RWT led to a pronounced increase in inositol phosphate formation due to phospholipase C-gamma (PLC-gamma) activation, PDGF-BB induced phosphoinositol hydrolysis was completely abolished in the F1021 and F1009/F1021 infectants, GF 109203X, a specific inhibitor of protein kinase C (PKC) activation, fully blocked PDGF-beta R-mediated monocytic differentiation and mitogenesis, Taken together, these results suggest that stimulation of the PDGF-beta R signaling pathway can mediate monocytic differentiation when PDGF-beta R is expressed at sufficient levels and that activation of PLC-gamma and PKC plays a pivotal role in PDGF-beta R-mediated differentiation and mitogenesis in FDC-P2 cell system. C1 NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NIDR,MOL SIGNALING UNIT,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. LITHUANIA ACAD SCI,INST BIOCHEM,LT-2600 VILNIUS,LITHUANIA. HARVARD UNIV,SCH MED,SCHEPENS EYE RES INST,BOSTON,MA 02114. RI Gutkind, J. Silvio/A-1053-2009 FU NCI NIH HHS [CA55063]; NIGMS NIH HHS [GM48339] NR 31 TC 26 Z9 26 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 31 PY 1997 VL 15 IS 5 BP 585 EP 593 DI 10.1038/sj.onc.1201221 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XN255 UT WOS:A1997XN25500010 PM 9247312 ER PT J AU Li, Q Notkins, AL Lan, MS AF Li, Q Notkins, AL Lan, MS TI Molecular characterization of the promoter region of a neuroendocrine tumor marker, IA-1 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID INSULIN-II GENE; TRANSCRIPTIONAL ELEMENTS; LESS PROMOTER; DNA-BINDING; CELL-LINES; RAT; EXPRESSION; ENHANCER; INITIATION; SEQUENCES AB IA-1 is an intronless gene, which encodes a 510 amino acid protein with a zinc-finger DNA-binding motif that is expressed in tumors of neuroendocrine origin, The 5'-upstream region of the IA-1 gene was recently sequenced. In this paper, the regulatory elements and the promoter region of the 5'-upstream region were analyzed by use of a series of deletion mutants (ranging from +26 bp to -2090 bp upstream of the IA-1 gene), which were tested in a pituitary tumor cell line, AtT-20, and Hela cells by transient transfection assays. These experiments showed that a 506 base pair upstream sequence was sufficient for maximal expression of a reporter gene. Multiple known regulatory elements were found within this region including three E boxes and a clustered Sp-1 site. In addition, Southwestern blot analysis, using a radiolabeled promoter sequence (extending from -108 bp to -66 bp) and nuclear extracts from both neuroendocrine and non-neuroendocrine cell lines, revealed four promoter binding proteins designated PBP1, PBP2, PBP3 and PBP4 with molecular weights of 55 kD, 32 kD, 29 kD, and 27/28 kD, respectively. These studies suggest that several different regulatory elements in the 5'-upstream region of the IA-1 gene and at least four different nuclear proteins may be involved in the cell-specific expression of IA-1. (C) 1997 Academic Press. C1 NIDR,ORAL INFECT & IMMUN BRANCH,NIH,BETHESDA,MD 20892. NR 18 TC 11 Z9 11 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 30 PY 1997 VL 236 IS 3 BP 776 EP 781 DI 10.1006/bbrc.1997.7054 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XQ533 UT WOS:A1997XQ53300049 PM 9245732 ER PT J AU Thompson, PA Eaton, WA Hofrichter, J AF Thompson, PA Eaton, WA Hofrichter, J TI Laser temperature jump study of the helix reversible arrow coil kinetics of an alanine peptide interpreted with a 'kinetic zipper' model SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; ALPHA-HELIX; CIRCULAR-DICHROISM; ELECTRIC-FIELD; TRANSITION; DYNAMICS; WATER; ACID); EQUILIBRIUM; SIMULATIONS AB The kinetics of the helix reversible arrow coil transition of an alanine-based peptide following a laser-induced temperature jump were monitored by the fluorescence of an N-terminal probe, 4-(methylamino)benzoic acid (MABA). This probe forms a peptide hydrogen bond to the helix backbone, which changes its fluorescence quantum yield. The MABA fluorescence intensity decreases in a single exponential relaxation, with relaxation times that are weakly temperature dependent, exhibiting a maximum value of similar to 20 ns near the midpoint of the melting transition. We have developed a new model, the kinetic version of the equilibrium 'zipper' model for helix reversible arrow coil transitions to explain these results. In this 'kinetic zipper' model, an enormous reduction in the number of possible species results from the assumption that each molecule contains either no helical residues or a single contiguous region of helix (the single-sequence approximation). The decay of the fraction of N-terminal residues that are helical, calculated from numerical solutions of the kinetic equations which describe the model, can be approximately described by two exponential relaxations having comparable amplitudes. The shorter relaxation time results from rapid unzipping (and zipping) of the helix ends in response to the temperature jump, while the longer relaxation time results from equilibration of helix-containing and non-helix-containing structures by passage over the nucleation free energy barrier. The decay of the average helix content is dominated by the slower process. The model therefore explains the experimental observation that relaxation for the N-terminal fluorescent probe is similar to 8-fold faster than that for the infrared probe of Williams et al. [(1996) Biochemistry 35, 691-697], which measures the average helix content, but does not account far the absence of observable amplitude for the slow relaxation in the fluorescence experiments (<10% slow phase). If we assume that the activation barrier for the coil-->helix rate is purely entropic, the model can also explain the maximum in the temperature dependence of the relaxation time for the fluorescent probe. Parameters that best reproduce the melting curves and the ratio of relaxation times predict a value of the cooperativity parameter sigma which is similar to 3-fold larger than previously reported values obtained from fitting equilibrium data only. The helix growth rate of similar to 10(8) s(-1) that reproduces the experimental relaxation times is similar to 100-fold slower than those observed in molecular dynamics simulations. These parameters can be used to simulate the kinetically cooperative formation of a helix from the all-coil state. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 64 TC 332 Z9 335 U1 2 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 29 PY 1997 VL 36 IS 30 BP 9200 EP 9210 DI 10.1021/bi9704764 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XN574 UT WOS:A1997XN57400015 PM 9230053 ER PT J AU PerezPerez, GI Bhat, N Gaensbauer, J Fraser, A Taylor, DN Kuipers, EJ Zhang, L You, WC Blaser, MJ AF PerezPerez, GI Bhat, N Gaensbauer, J Fraser, A Taylor, DN Kuipers, EJ Zhang, L You, WC Blaser, MJ TI Country-specific constancy by age in cagA(+) proportion of Helicobacter pylori infections SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GASTRIC-CARCINOMA; DUODENAL-ULCER; RISK; EXPRESSION; CANCER; ADENOCARCINOMA; SEROPREVALENCE; CYTOTOXICITY; CHILDHOOD; ANTIGEN AB Helicobacter pylori strains may be either cagA(+) or cagA(-), and in logitudinal studies, infection with a cagA(+) strain has been associated with increased risk for the development of atrophic gastritis and cancer of the distal stomach. We sought to determine the relative proportion of strains producing CagA in different geographic locales, and the extent to which CagA seroprevalence varied in countries with different gastric and esophageal cancer rates. Using an enzyme-linked immunosorbent assay (ELISA) to detect serum IgG to CagA, we examined sera from 468 asymptomatic H. pylori-infected adults from Canada, Peru, China, Thailand, The Netherlands and 3 different ethnic groups in New Zealand. The CagA seroprevalence in Peru and Thailand (82.2% and 78.8%, respectively) were each substantially higher than for the Chinese (37.9%), Canadian (41.9%), Dutch (39.0%) and New Zealand (28.2%) subjects, but within each population, rates were relatively constant across gender and age groups. Reported gastric but not esophageal cancer rates for the 8 studied populations were significantly associated with H. pylori seroprevalence. Variation in CagA positivity rates was not significantly associated with variation in either gastric or esophageal cancer rates. Our data suggest that CagA seroprevalence is not the major factor influencing gastric cancer rates. (C) 1997 Wiley-Liss, Inc. C1 UNIV AUCKLAND,AUCKLAND 1,NEW ZEALAND. USN,MED RES INST DETACHMENT,LIMA,PERU. FREE UNIV AMSTERDAM HOSP,AMSTERDAM,NETHERLANDS. BEIJING INST CANC RES,BEIJING,PEOPLES R CHINA. NCI,BETHESDA,MD 20892. DEPT VET AFFAIRS MED CTR,NASHVILLE,TN 37212. RP PerezPerez, GI (reprint author), VANDERBILT UNIV,SCH MED,DIV INFECT DIS,A-3310 MED CTR N,1161 21ST AVE S,NASHVILLE,TN 37232, USA. FU NIDDK NIH HHS [R01DK50837] NR 36 TC 88 Z9 91 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 29 PY 1997 VL 72 IS 3 BP 453 EP 456 DI 10.1002/(SICI)1097-0215(19970729)72:3<453::AID-IJC13>3.0.CO;2-D PG 4 WC Oncology SC Oncology GA XM692 UT WOS:A1997XM69200013 PM 9247289 ER PT J AU Funatomi, H Itakura, J Ishiwata, T Pastan, I Thompson, SA Johnson, GR Korc, M AF Funatomi, H Itakura, J Ishiwata, T Pastan, I Thompson, SA Johnson, GR Korc, M TI Amphiregulin antisense oligonucleotide inhibits the growth of T3M4 human pancreatic cancer cells and sensitizes the cells to EGF receptor-targeted therapy SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MAMMARY EPITHELIAL-CELLS; FACTOR-ALPHA; FACTOR FAMILY; EXPRESSION; BINDING; LINE; CARCINOMAS; INDUCTION; MEMBER; GENE AB Human pancreatic cancers overexpress the epidermal growth factor (EGF) receptor (EGFR) and all 5 ligands that bind to this receptor, including amphiregulin. It is not known, however, whether amphiregulin contributes in an autocrine manner to enhance pancreatic cancer cell growth, Therefore, we used an amphiregulin antisense oligonucleotide (AR-AS) to suppress amphiregulin expression in T3M4 human pancreatic cancer cells, These cells express high levels of EGFR and amphiregulin. AR-AS abolished amphiregulin immunoreactivity in T3M4 cells, decreased amphiregulin release into the medium and inhibited cell growth in a dose-dependent manner, Exogenous amphiregulin reversed AR-AS-mediated growth inhibition, A random oligonucleotide (AR-R) did not alter either cell growth or cellular amphiregulin immunoreactivity, AR-AS also increased cellular EGFR protein levels and enhanced the growth inhibitory actions of TP40, a chimeric protein consisting of transforming growth factor-alpha coupled to Pseudomonas exotoxin that internalizes into cells via EGFR, These findings indicate that there is an important EGFR/amphiregulin autocrine loop in T3M4 cells and raise the possibility that modalities aimed at abrogating amphiregulin action may prove useful in pancreatic cancer, especially when used in conjunction with EGFR-targeted therapy. (C) 1997 Wiley-Liss, Inc. C1 UNIV CALIF IRVINE,DIV ENDOCRINOL DIABET & METAB MED SCI 1,DEPT MED,IRVINE,CA 92697. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92697. UNIV CALIF IRVINE,DEPT PHARMACOL,IRVINE,CA 92697. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. BERLEX BIOSCI,RICHMOND,CA. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. FU NCI NIH HHS [CA-4062] NR 34 TC 51 Z9 52 U1 2 U2 5 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 JUL 29 PY 1997 VL 72 IS 3 BP 512 EP 517 DI 10.1002/(SICI)1097-0215(19970729)72:3<512::AID-IJC21>3.0.CO;2-C PG 6 WC Oncology SC Oncology GA XM692 UT WOS:A1997XM69200021 PM 9247297 ER PT J AU Merchenthaler, I Maderdrut, JL Cianchetta, P Shughrue, P Bronstein, D AF Merchenthaler, I Maderdrut, JL Cianchetta, P Shughrue, P Bronstein, D TI In situ hybridization histochemical localization of prodynorphin messenger RNA in the central nervous system of the rat SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE brain; chemical neuroanatomy; dynorphin; opioid peptides; riboprobe; spinal cord ID DYNORPHIN-IMMUNOREACTIVE NEURONS; THYROTROPIN-RELEASING-HORMONE; GENE-RELATED PEPTIDE; INSITU HYBRIDIZATION; SUBSTANCE-P; TYROSINE-HYDROXYLASE; NUCLEUS-ACCUMBENS; CEREBRAL-CORTEX; NEUROKININ-B; SPINAL-CORD AB The distribution of preprodynorphin messenger RNA-containing perikarya in the central nervous system of the rat was determined with in situ hybridization histochemistry using a S-35-labelled complementary RNA probe. All of the regions of the central nervous system reported by other investigators to contain perikarya that synthesize prodynorphin-derived peptides, except the pedunculopontine tegmental nucleus, the accessory trigeminal nucleus, and the ventral nucleus of the trapezoid body, also contained perikarya that synthesize preprodynorphin messenger RNA. However, the olfactory bulb, the anterior olfactory nucleus, the islands of Calleja, the CA1-CA3 fields of the hippocampus, the septohippocampal nucleus, the diagonal band of Broca, the basal and cortical amygdaloid nuclei, the entopeduncular nucleus, the subthalamic nucleus, the superior colliculus, the Edinger-Westphal nucleus, the dentate nucleus, the raphes linearis and pontis, the dorsal cochlear nucleus, the medial vestibular nucleus, the inferior olive, and the dorsal motor nucleus of the vagus nerve also contained preprodynorphin messenger RNA-synthesizing perikarya. These observations suggest that prodynorphin-derived peptides have a much more pervasive role in central nervous system function than previously suspected. However, before the physiological significance of these observations can be judged, it will be necessary to determine whether all of the novel sites of preprodynorphin messenger RNA synthesis are sites of prohormone synthesis and conventional processing. C1 NIEHS,MOL & INTEGRAT NEUROSCI LAB,FUNCT MORPHOL SECT,RES TRIANGLE PK,NC 27709. WYETH AYERST RES,WOMENS HLTH RES INST,RADNOR,PA 19087. TULANE UNIV,HEBERT CTR,US JAPAN BIOMED RES LABS,DEPT MED,BELLE CHASSE,LA 70037. NIEHS,MOL & INTEGRAT NEUROSCI LAB,PHARMACOL SECT,RES TRIANGLE PK,NC 27709. NR 58 TC 41 Z9 41 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 28 PY 1997 VL 384 IS 2 BP 211 EP 232 PG 22 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA XH829 UT WOS:A1997XH82900004 PM 9215719 ER PT J AU Couceyro, P Shoaib, M McCoy, M Goldberg, SR Kuhar, MJ AF Couceyro, P Shoaib, M McCoy, M Goldberg, SR Kuhar, MJ TI Cocaine self-administration alters brain NADH dehydrogenase mRNA levels SO NEUROREPORT LA English DT Article DE cocaine; differential display; drugs of abuse; gene regulation; mitochondria; NADH dehydrogenase; PCR; self-administration; transcription ID MESSENGER-RNA; RAT-BRAIN; C-FOS; DIFFERENTIAL DISPLAY; REWARD REGIONS; WITHDRAWAL; STRIATUM; AMPHETAMINE; PATHWAYS; SYSTEM AB USING differential display PCR, we identified a cDNA whose expression is altered in several brain regions in rats self-administering cocaine. The cDNA sequence corresponds to bases 13687-13723 of the rat NADH dehydrogenase subunit 6 gene. Northern analysis indicated a 26% decrease in nucleus accumbens, a 305% increase in the ventral midbrain and no changes in the caudate putamen mRNA levels; changes were also noted in the hypothalamus and cerebellum. This is the first demonstration of an effect of cocaine self-administration on mitochondrial gene expression and suggests that regional metabolic changes elicited by cocaine may be relevant to and involved in its reinforcing properties. C1 EMORY UNIV,YERKES REG PRIMATE RES CTR,DIV NEUROSCI,ATLANTA,GA 30329. NIDA,LAB MOL PSYCHIAT,NIH,BALTIMORE,MD. NIDA,PRECLIN PHARMACOL LAB,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD. FU NCRR NIH HHS [RR00165] NR 19 TC 8 Z9 8 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 JUL 28 PY 1997 VL 8 IS 11 BP 2437 EP 2441 DI 10.1097/00001756-199707280-00006 PG 5 WC Neurosciences SC Neurosciences & Neurology GA XP313 UT WOS:A1997XP31300009 PM 9261805 ER PT J AU Grady, CL VanMeter, JW Maisog, JM Pietrini, P Krasuski, J Rauschecker, JP AF Grady, CL VanMeter, JW Maisog, JM Pietrini, P Krasuski, J Rauschecker, JP TI Attention-related modulation of activity in primary and secondary auditory cortex SO NEUROREPORT LA English DT Article DE attention; audition; human; neuroimaging; perception ID SELECTIVE ATTENTION; BRAIN POTENTIALS AB WE investigated the effects of auditory attention on brain activity using functional magnetic resonance imaging. Subjects listened to three word lists, three times each, and were instructed to count the number of times they heard a target word during two of these presentations. For the third, they listened to the words without counting. All subjects showed significant areas of activation in auditory cortex during the listening conditions compared to rest. There was significantly more activation and a larger area of activation, particularly in association cortex, in the left temporal lobe during counting of targets compared to the no-target conditions, with a similar trend in the right hemisphere. These results provide evidence of an attention-related enhancement of both activation magnitude and extent in auditory cortex. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NIMH,LAB BRAIN & COGNIT,BETHESDA,MD 20892. GEORGETOWN UNIV,INST COGNIT & COMPUTAT SCI,WASHINGTON,DC. RI Rauschecker, Josef/A-4120-2013 NR 25 TC 121 Z9 121 U1 0 U2 6 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 28 PY 1997 VL 8 IS 11 BP 2511 EP 2516 DI 10.1097/00001756-199707280-00019 PG 6 WC Neurosciences SC Neurosciences & Neurology GA XP313 UT WOS:A1997XP31300022 PM 9261818 ER PT J AU Pigarev, IN Nothdurft, HC Kastner, S AF Pigarev, IN Nothdurft, HC Kastner, S TI Evidence for asynchronous development of sleep in cortical areas SO NEUROREPORT LA English DT Article DE area V4; development of sleep; monkey; neuronal activity; sleep; visual cortex ID NEURONS AB WE have recorded from extrastriate area V4 in monkeys performing a visual search task. When animals became tired or drowsy, responses to visual stimulation were often reduced or even completely blocked, and background activity changed to the burst-pause pattern typically seen in sleep. In spite of such neuronal sleep observed in V4, animals continued to perform the visual task, indicating that at least the primary visual cortex was still working. This observation shows that sleep does not develop simultaneously in all cortical areas but may affect some areas earlier than others. In particular conditions, local sleep of certain areas may be a stable and long-lasting phenomenon. C1 MAX PLANCK INST BIOPHYS CHEM,AG NEUROBIOL,D-37018 GOTTINGEN,GERMANY. RUSSIAN ACAD SCI,INST PROBLEMS INFORMAT TRANSMISS,MOSCOW 101447,RUSSIA. NIMH,LAB BRAIN & COGNIT,LPP,BETHESDA,MD 20892. NR 8 TC 67 Z9 70 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 28 PY 1997 VL 8 IS 11 BP 2557 EP 2560 DI 10.1097/00001756-199707280-00027 PG 4 WC Neurosciences SC Neurosciences & Neurology GA XP313 UT WOS:A1997XP31300030 PM 9261826 ER PT J AU Taha, TE Biggar, RJ Broadhead, RL Mtimavalye, LAR Justesen, AB Liomba, GN Chiphangwi, JD Miotti, PG AF Taha, TE Biggar, RJ Broadhead, RL Mtimavalye, LAR Justesen, AB Liomba, GN Chiphangwi, JD Miotti, PG TI Effect of cleansing the birth canal with antiseptic solution on maternal and newborn morbidity and mortality in Malawi: Clinical trial SO BRITISH MEDICAL JOURNAL LA English DT Article ID VAGINAL CHLORHEXIDINE DISINFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; GROUP-B STREPTOCOCCI; VERTICAL TRANSMISSION; INFECTION; INFANT; LABOR AB Objective: To determine if cleansing the birth canal with an antiseptic at del Design: Clinical trial; two months of no intervention were followed by three months of intervention and a final month of no intervention. Setting: Queen Elizabeth Central Hospital (tertiary care urban hospital), Blantyre, Malawi. Subjects: A total of 6965 women giving birth in a six month period and their 7160 babies. Intervention: Manual wipe of the maternal canal with a 0.25% chlorhexidine solution at every vaginal examination before delivery. Babies born during the intervention were also wiped with chlorhexidine. Main Outcome Measures: Effects of the intervention on neonatal and maternal morbidity and mortality. Results: 3635 women giving birth to 3743 babies were enrolled in the intervention phase and 3330 women giving birth to 3417 babies were enrolled in the non-intervention phase, There were no adverse reactions related to the intervention among the mothers al their children. Among infants bent in the intervention phase, overall neonatal admissions were reduced (634/3743 (16.9%) v 661/3417 (19.3%), P < 0.01), as were admissions for neonatal sepsis (7.8 v 17.9 per 1000 live births, P < 0.0002), overall neonatal mortality (28.6 v 36.9 per 1000 live births, P < 0.06), and mortality due to infectious causes (2.4 v 7.3 per 1000 Live births, P < 0.005). Among mothers receiving the intervention, admissions related to delivery were reduced (29.4 v 40.2 per 1000 deliveries, P< 0.02). as iz ere admissions due to postpartum infections (1.7 v 5.1 per 1000 deliveries, P = 0.02) and duration of hospitalisation (Wilcoxan P = 0.008). Conclusions: Cleansing the birth canal with chlorhexidine reduced early neonatal and maternal postpartum infectious problems, The safety, simplicity and low cost of the procedure suggest that it should be considered as standard care to lower infant and maternal morbidity and mortality. C1 NCI, VIRAL EPIDEMIOL BRANCH, BETHESDA, MD 20852 USA. UNIV MALAWI, COLL MED, BLANTYRE, MALAWI. RP Taha, TE (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, INFECT DIS PROGRAMME, RM E6011, BALTIMORE, MD 21205 USA. RI Sandall, Jane/D-4146-2009 OI Sandall, Jane/0000-0003-2000-743X NR 12 TC 102 Z9 104 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD JUL 26 PY 1997 VL 315 IS 7102 BP 216 EP 219 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XN517 UT WOS:A1997XN51700021 PM 9253269 ER PT J AU Rothman, N Cantor, KP Blair, A Bush, D Brook, JW Helzlsouer, K Zahm, SH Needham, LL Pearson, GR Hoover, RN Comstock, GW Strickland, PT AF Rothman, N Cantor, KP Blair, A Bush, D Brook, JW Helzlsouer, K Zahm, SH Needham, LL Pearson, GR Hoover, RN Comstock, GW Strickland, PT TI A nested case-control study of non-Hodgkin lymphoma and serum organochlorine residues SO LANCET LA English DT Article ID POLYCHLORINATED-BIPHENYLS; CANCER MORTALITY; DIETARY FACTORS; WORKERS; CONSUMPTION; EXPOSURE AB Background The steady worldwide increase in the incidence of non-Hodgkin lymphoma during the past few decades remains mostly unexplained. Several studies suggest that there may be an association between the agricultural use of the organochlorine 1,1,1-trichloro-2,2'bis(p-chlorophenyl)ethane (DDT) and increased. risk of non-Hodgkin lymphoma. We have investigated the association between risk of non-Hodgkin lymphoma and body burden of selected organochlorines in the general population in a nested case-control study. Methods We measured prediagnostic serum concentrations of DDT, its metabolites, and other organochlorines, including polychlorinated biphenyls (PCBs), in 74 cases of non-Hodgkin lymphoma and 147 matched controls identified from a prospective cohort of 25 802 adults, established in 1974 in Washington County, Maryland, USA. We report results for total lipid-corrected serum concentrations of DDT and total PCBs. Findings There was a strong dose-response relation between quartiles of total lipid-corrected serum PCB concentrations and risk of non-Hodgkin lymphoma overall (odds ratios by quartile: 1.0; 1.3 [95% CI 0.5-3.3]; 2-8 [1.1-7.6]); and 4.5 [1.7-12.0]; p for trend=0.0008) and separately in men and in women. There was also evidence suggesting that seropositivity for the Epstein-Barr virus early antigen potentiated the effects of serum PCBs. By contrast, total lipid-corrected serum concentrations of DDT were not associated with risk of non-Hodgkin lymphoma. Interpretation These results should be regarded as hypothesis-generating. Before causal inferences can be made about exposure to PCBs and increased risk of non-Hodgkin lymphoma, our findings require replication and the biological plausibility of the association needs further investigation. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD. CTR DIS CONTROL & PREVENT,NATL CTR ENVIRONM HLTH,ATLANTA,GA. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. RP Rothman, N (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892, USA. RI Needham, Larry/E-4930-2011; Zahm, Shelia/B-5025-2015 FU NCI NIH HHS [CA60754]; NHLBI NIH HHS [HL21670]; NIEHS NIH HHS [ES03819] NR 32 TC 131 Z9 137 U1 1 U2 5 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 26 PY 1997 VL 350 IS 9073 BP 240 EP 244 DI 10.1016/S0140-6736(97)02088-6 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XM866 UT WOS:A1997XM86600010 PM 9242800 ER PT J AU Pack, S Vortmeyer, AO Pak, E Liotta, LA Zhuang, ZP AF Pack, S Vortmeyer, AO Pak, E Liotta, LA Zhuang, ZP TI Detection of gene deletion in single metastatic tumour cells in lymphnode tissue by fluorescent in-situ hybridisation SO LANCET LA English DT Article C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RI Pack, Svetlana/C-2020-2014 NR 3 TC 6 Z9 6 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 26 PY 1997 VL 350 IS 9073 BP 264 EP 265 DI 10.1016/S0140-6736(05)62228-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XM866 UT WOS:A1997XM86600019 PM 9242809 ER PT J AU Goldman, D Urbanek, R Guenther, D Robin, R Long, JC AF Goldman, D Urbanek, R Guenther, D Robin, R Long, JC TI Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism, substance abuse and schizophrenia in southwestern American Indians SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE dopamine; sib-pair linkage; linkage disequilibrium ID DOPAMINE-D2 RECEPTOR GENE; ALLELIC ASSOCIATION; A1 ALLELE; LOCUS; RFLP; DISEQUILIBRIUM; GENOTYPE; ACID AB Alcoholism is one of a group of common psychiatric diseases which are well-defined clinically and strongly influenced genetically, but which are likely to be highly heterogeneous in causation, genetically and otherwise, Dopamine is a key neurotransmitter in drug-mediated reinforcement, Based on association studies with the Taq1A downstream marker, the D2 dopamine receptor has been proposed to be the ''Reward Deficiency Syndrome Gene,'' Ser311Cys, a naturally occurring variant which largely inactivates transduction after D2 receptor activation, was abundant (0.16) in a Southwestern American Indian population we studied. Therefore, we were able to provide a critical test of the D2 hypothesis of vulnerability to alcoholism by evaluating Ser311Cys and also the intron-2 STR and Taq1A markers at this locus in a total of 459 subjects, including 373 sib pairs, from large families, The result is that neither alcoholism, substance use disorders nor schizophrenia show a relationship to Ser311Cys genotype, even when the 15 Cys311/Cys311 homozygous individuals are compared to others, Furthermore, sib pair analysis incorporating information across all three sib pair categories: concordant affected, discordant and concordant unaffected revealed no effect of DRD2 genotype or haplotype on alcoholism or substance use disorder. (C) 1997 Wiley-Liss, Inc. RP Goldman, D (reprint author), NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NCRR NIH HHS [1 P41 RR03655] NR 38 TC 67 Z9 69 U1 1 U2 2 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 JUL 25 PY 1997 VL 74 IS 4 BP 386 EP 394 DI 10.1002/(SICI)1096-8628(19970725)74:4<386::AID-AJMG9>3.0.CO;2-N PG 9 WC Genetics & Heredity SC Genetics & Heredity GA XP268 UT WOS:A1997XP26800009 PM 9259374 ER PT J AU Vandenbergh, DJ Rodriguez, LA Miller, IT Uhl, GR Lachman, HM AF Vandenbergh, DJ Rodriguez, LA Miller, IT Uhl, GR Lachman, HM TI High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE abuse; cocaine; opiates; polymorphism; dopamine ID GENE; ASSOCIATION; PHARMACOGENETICS; POLYMORPHISM; EXPRESSION; CLONING; DRUG AB Allelic variants at the catechol-O-methyltransferase (COMT) locus are candidates to contribute to genetic components of interindividual differences in vulnerability to substance abuse, COMT plays a prominent role in dopaminergic circuits important for drug reward, and CORIT alleles encode enzymes whose activities vary from three- to fourfold. We compared COMT allele frequencies in control research volunteers reporting insignificant lifetime use of addictive substances with those in volunteers reporting substantial polysubstance use, Homozygosity for the high-activity COMT allele was found in 18% of controls, 31% of volunteers with high lifetime substance use, and 39% meeting DSMIII-R substance abuse criteria [odds ratio (relative risks) 2.0 (control vs, use; 95% confidence interval 1.2-3.5; P < 0.013) and 2.8 (control vs. DSM; 1.3-6.1; P < 0.008)], Individuals with the high-activity COMT variant may have greater genetic vulnerability to drug abuse. (C) 1997 Wiley-Liss, Inc. C1 ALBERT EINSTEIN COLL MED,DEPT MED,BRONX,NY 10461. ALBERT EINSTEIN COLL MED,DEPT PSYCHIAT,BRONX,NY 10461. NIDA,MOL NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NR 25 TC 131 Z9 139 U1 2 U2 5 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 JUL 25 PY 1997 VL 74 IS 4 BP 439 EP 442 DI 10.1002/(SICI)1096-8628(19970725)74:4<439::AID-AJMG16>3.0.CO;2-J PG 4 WC Genetics & Heredity SC Genetics & Heredity GA XP268 UT WOS:A1997XP26800016 PM 9259381 ER PT J AU Gejman, PV AF Gejman, PV TI Ernst Rudin and Nazi euthanasia: Another stain on his career SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter RP Gejman, PV (reprint author), NIMH,UNIT MOL CLIN INVEST,CLIN NEUROGENET BRANCH,IRP,NIH,BLDG 10,ROOM 4N320,10 CTR DR,MSC 1384,BETHESDA,MD 20892, USA. NR 11 TC 13 Z9 13 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 25 PY 1997 VL 74 IS 4 BP 455 EP 456 DI 10.1002/(SICI)1096-8628(19970725)74:4<455::AID-AJMG22>3.0.CO;2-G PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XP268 UT WOS:A1997XP26800022 PM 9259387 ER PT J AU Gershon, ES AF Gershon, ES TI Ernst Rudin, a Nazi psychiatrist and geneticist SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Letter RP Gershon, ES (reprint author), NIMH,CLIN NEUROGENET BRANCH 103N218,BETHESDA,MD 20892, USA. NR 7 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 25 PY 1997 VL 74 IS 4 BP 457 EP 458 DI 10.1002/(SICI)1096-8628(19970725)74:4<457::AID-AJMG23>3.0.CO;2-G PG 2 WC Genetics & Heredity SC Genetics & Heredity GA XP268 UT WOS:A1997XP26800023 PM 9259388 ER PT J AU Kauppila, LI Polak, JF Cupples, LA Hannan, MT Kiel, DP Wilson, PWF AF Kauppila, LI Polak, JF Cupples, LA Hannan, MT Kiel, DP Wilson, PWF TI New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: A 25-year follow-up study SO ATHEROSCLEROSIS LA English DT Article DE aortic calcification; atherosclerosis; epidemiological study ID ATHEROSCLEROSIS AB The purpose of the present study was to assess the location, severity and progression of radiopaque lumbar aortic calcifications and to evaluate the utility of summary scores of lumbar calcification in a population-based cohort. Lateral lumbar films, obtained in 617 Framingham heart study participants, were analysed for the presence of abdominal aortic wall calcification in the region corresponding to the first through fourth lumbar vertebrae. The severity of the anterior and posterior aortic calcification were graded individually on a 0-3 scale for each lumbar segment and the results were summarized to develop four different composite scores: (1) affected segments score (range 0-4); (2) anterior and posterior affected score (range 0-8); and (3) antero-posterior severity score (range 0-24). The prevalence of aortic calcification was 37% in men and 27% in women at baseline and 86% in both genders al the follow-up exam 25 years later. During the follow-up interval, the mean of the affected segments score increased from 0.7 in men (0.5 in women) to 2.7 (2.8 in women), the mean of the anterior and posterior affected score from 1.2 (0.8 in women) (P = 0.012 for difference between genders) and the mean of the antero-posterior severity score increased from 1.5 (1.3 in women) to 9.3 (10.3 in women). The antero-posterior severity score offered a slight advantage over other composite scores and had the highest inter-rater intra-class correlations. In summary, lumbar aortic calcification can be graded and composite summary scores are reproducible. This technique appears to provide a simple, low cost assessment of subclinical vascular disease. (C) 1997 Elsevier Science Ireland Ltd. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. BOSTON UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,BOSTON,MA 02118. NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA 01701. HEBREW REHABIL CTR AGED,BOSTON,MA 02131. HARVARD UNIV,SCH MED,BOSTON,MA 02131. OI Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-38038] NR 16 TC 238 Z9 262 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JUL 25 PY 1997 VL 132 IS 2 BP 245 EP 250 DI 10.1016/S0021-9150(97)00106-8 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XL447 UT WOS:A1997XL44700015 PM 9242971 ER PT J AU Fasciano, J Steele, T Castagnoli, N Katz, J Ricaurte, G AF Fasciano, J Steele, T Castagnoli, N Katz, J Ricaurte, G TI The effect of N-methylation on fenfluramine's neurotoxic and pharmacologic actions SO BRAIN RESEARCH LA English DT Article DE serotonin; neurotoxicity; anorexia; discriminative stimulus effect; fenfluramine; amphetamine ID DISCRIMINATIVE STIMULUS PROPERTIES; TYROSINE-HYDROXYLASE ACTIVITY; RAT-BRAIN; SEROTONIN NEUROTOXICITY; TRYPTOPHAN-HYDROXYLASE; PARA-CHLOROAMPHETAMINE; STRIATAL DOPAMINE; UPTAKE SITES; AMPHETAMINE; METHAMPHETAMINE AB N-Methylation separates methamphetamine's neurotoxic and pharmacologic effects. In particular, N-methylation eliminates methamphetamine's neurotoxic activity while preserving its behavioral pharmacologic activity. The purpose of the present studies was to determine whether N-methylation could also be used to separate fenfluramine's neurotoxic and pharmacologic effects. Fenfluramine-induced serotonin neurotoxicity was assessed by measuring serotonin axonal markers 2 weeks after fenfluramine administration. Pharmacologic effects of fenfluramine were assessed by measuring fenfluramine-induced anorexia and fenfluramine discrimination. Both fenfluramine and its N-methylated analog, N-methylfenfluramine, produced dose-related effects in food intake, drug-discrimination and neurotoxicity studies. Although N-methylation reduced the neurotoxic potency of fenfluramine, it also reduced its pharmacologic activity. Neurotoxic potency was reduced 4- to 8-fold (depending on brain region), while pharmacologic potency was reduced 4- to 10-fold (depending on paradigm). Notably, N-methylation did not change the efficacy of fenfluramine as a serotonin neurotoxin, anorectic agent or discrimination stimulus. These results indicate that fenfluramine's behavioral and neurotoxic effects, unlike those of methamphetamine, are not dissociated by N-methylation. Further, the present results suggest that the effectiveness of side-chain nitrogen substitution in separating the behavioral and neurotoxic effects of amphetamine derivatives is strongly influenced by ring substitutions. (C) 1997 Elsevier Science B.V. C1 JOHNS HOPKINS MED INST, DEPT NEUROL, BALTIMORE, MD 21224 USA. VIRGINIA POLYTECH INST & STATE UNIV, DEPT CHEM, BALTIMORE, MD 21224 USA. NIDA, ADDICT RES CTR, PSYCHOBIOL SECT, BALTIMORE, MD 21224 USA. OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [R01 DA06275, K02 DA00206] NR 51 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 25 PY 1997 VL 763 IS 2 BP 182 EP 190 DI 10.1016/S0006-8993(97)00110-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XT038 UT WOS:A1997XT03800004 PM 9296558 ER PT J AU Zhang, L Joseph, JA Roth, GS AF Zhang, L Joseph, JA Roth, GS TI Effect of aging on vulnerability of striatal D-1 and D-2 dopamine receptor-containing neurons to kainic acid SO BRAIN RESEARCH LA English DT Article DE aging; D-1 and D-2 dopamine receptors; kainic acid ID BRAIN; RATS AB Kainic acid lesions elicit reductions in ligand binding to both D-1 and D-2 striata dopamine receptors in young and old rats. Relative reductions are greatest for both receptors in young animals than old. In addition, D-1 receptor binding is reduced more than D-2 at both ages. These findings support the idea that those dopamine receptor neurons lost during aging may reside in a kainic acid sensitive population. (C) 1997 Elsevier Science B.V. C1 NIA,MOL PHYSIOL & GENET SECT,CELLULAR & MOL BIOL LAB,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. CHINESE UNIV HONG KONG,FAC MED,DEPT ANAT,SHATIN,NT,HONG KONG. TUFTS UNIV,USDA ARS NHRCA,BOSTON,MA 02111. NR 15 TC 4 Z9 4 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 JUL 25 PY 1997 VL 763 IS 2 BP 264 EP 266 DI 10.1016/S0006-8993(97)00485-X PG 3 WC Neurosciences SC Neurosciences & Neurology GA XT038 UT WOS:A1997XT03800015 PM 9296569 ER PT J AU Gfroerer, J Wright, D Kopstein, A AF Gfroerer, J Wright, D Kopstein, A TI Prevalence of youth substance use: the impact of methodological differences between two national surveys SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE drugs; questionnaires; methodological differences ID DRUG-USE; RELIABILITY; VALIDITY AB This study compared two major Federally sponsored surveys of adolescent substance use and assessed the impact that methodological differences have on the prevalence estimates they generate. The Monitoring the Future Survey, a school-based survey, was compared to the National Household Survey on Drug Abuse, a household survey of the population aged 12 years and older. Response rates were higher in the household survey due to high rates of refusal in the school based survey. The school survey has a larger overall sample size, but sampling errors more similar than one might expect, because of the larger design effects in the school survey. Rates of drug use obtained were larger in the school survey than in the household survey, possibly because of greater under-reporting in the household setting than in the classroom and the different questionnaires used in the two surveys. (C) 1997 Elsevier Science Ireland Ltd. C1 NIDA,DIV EPIDEMIOL & PREVENT RES,ROCKVILLE,MD 20857. RP Gfroerer, J (reprint author), SUBSTANCE ABUSE & MENTAL HLTH SERV ADM,OFF APPL STUDIES,ROOM 16C-06,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 36 TC 87 Z9 87 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 25 PY 1997 VL 47 IS 1 BP 19 EP 30 DI 10.1016/S0376-8716(97)00063-X PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XR990 UT WOS:A1997XR99000003 PM 9279494 ER PT J AU Vaughan, M AF Vaughan, M TI Oxidative modification of macromolecules minireview series - Prologue SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Editorial Material RP Vaughan, M (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892, USA. NR 0 TC 30 Z9 31 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1997 VL 272 IS 30 BP 18513 EP 18513 DI 10.1074/jbc.272.30.18513 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XM342 UT WOS:A1997XM34200001 ER PT J AU Olive, M Krylov, D Echlin, DR Gardner, K Taparowsky, E Vinson, C AF Olive, M Krylov, D Echlin, DR Gardner, K Taparowsky, E Vinson, C TI A dominant negative to activation protein-1 (AP1) that abolishes DNA binding and inhibits oncogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GCN4 LEUCINE-ZIPPER; C-JUN; DIMERIZATION SPECIFICITY; INDUCED TRANSFORMATION; COILED COILS; GENE FAMILY; T-CELLS; FOS; TRANSCRIPTION; GROWTH AB We describe a dominant negative (DN) to activation protein-1 (AP1) that inhibits DNA binding in an equimolar competition, AP1 is a heterodimer of the oncogenes Fos and Jun, members of the bZIP family of transcription factors. The DN, termed A-Fos, consists of a newly designed acidic amphipathic protein sequence appended onto the N-terminus of the Fos leucine zipper, replacing the normal basic region critical for DNA binding. The acidic extension and the Jun basic region form a heterodimeric coiled coil structure that stabilizes the complex over 3000-fold and prevents the basic region of Jun from binding to DNA. Gel shift assays indicate that A Fos can inactivate the DNA binding of a Fos:Jun heterodimer in an equimolar competition. Transient transfection assays indicate that A-Pos inhibits Jun-dependent transactivation. Both the acidic extension and the Fos leucine zipper are critical for this inhibition. Expression of A-Fos in mouse fibroblasts inhibits focus formation more than colony formation, reflecting the ability of A-Fos to interfere with the AP1 biological functions in mammalian cells. This reagent is more potent than a deletion of either the Fos or Jun transactivation domain, which has been used previously as a dominant negative to AP1 activity. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. PURDUE UNIV,DEPT BIOL SCI,W LAFAYETTE,IN 47907. NR 49 TC 202 Z9 202 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 JUL 25 PY 1997 VL 272 IS 30 BP 18586 EP 18594 DI 10.1074/jbc.272.30.18586 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XM342 UT WOS:A1997XM34200016 PM 9228025 ER PT J AU Yan, SZ Huang, ZH Rao, VD Hurley, JH Tang, WJ AF Yan, SZ Huang, ZH Rao, VD Hurley, JH Tang, WJ TI Three discrete regions of mammalian adenylyl cyclase form a site for G(s alpha) activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-GAMMA-SUBUNITS; PROTEIN; ALPHA; FORSKOLIN; MODELS AB The interaction between the alpha subunit of G protein G(s) (G(s alpha)) and the two cytoplasmic domains of adenylyl cyclase (C-1 and C-2) is a key step in the stimulation of cAMP synthesis by hormones, Mutational analysis reveals that three discrete regions in the primary sequence of adenylyl cyclase affect the EC50 values for G(s alpha) activation and thus are the affinity determinants of G(s alpha). Based on the three-dimensional structure of C-2 forskolin dimer, these three regions (C-2, alpha 2, C-2 alpha 3/beta 4, and C-1 beta 1) are close together and form a negatively charged and hydrophobic groove the width of an alpha helix that can accommodate the positively charged adenylyl cyclase binding region of G(s alpha). Two mutations in the C-2 alpha 3/beta 4 region decrease the V-max values of G(s alpha) activation without an increase in the EC50 values, Since these three regions are distal to the catalytic site, the likely mechanism for G(s alpha) activation is to modulate the structure of the active site by controlling the orientation of the C-2 alpha 2 and alpha 3/beta 4 structures. C1 UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL SCI,CHICAGO,IL 60637. NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM53459] NR 28 TC 47 Z9 48 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1997 VL 272 IS 30 BP 18849 EP 18854 DI 10.1074/jbc.272.30.18849 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XM342 UT WOS:A1997XM34200052 PM 9228061 ER PT J AU Rumsey, SC Kwon, O Xu, GW Burant, CF Simpson, I Levine, M AF Rumsey, SC Kwon, O Xu, GW Burant, CF Simpson, I Levine, M TI Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID L-ASCORBIC-ACID; VITAMIN-C; HUMAN-NEUTROPHILS; XENOPUS OOCYTES; FRUCTOSE TRANSPORTER; TISSUE DISTRIBUTION; HUMAN-ERYTHROCYTES; GENE LOCALIZATION; DIABETES-MELLITUS; SKELETAL-MUSCLE AB Dehydroascorbic acid (DHA) is rapidly taken up by cells and reduced to ascorbic acid (AA). Using the Xenopus laevis oocyte expression system we examined transport of DHA and AA via glucose transporter isoforms GLUT1-5 and SGLT1, The apparent K-m of DHA transport via GLUT1 and GLUT3 was 1.1 +/- 0.2 and 1.7 +/- 0.3 mM, respectively, High performance liquid chromatography analysis confirmed 100% reduction of DHA to AA within oocytes, GLUT4 transport of DHA was only 2-4-fold above control and transport kinetics could not be calculated, GLUT2, GLUT5, and SGLT1 did not transport DHA and none of the isoforms transported AA. Radiolabeled sugar transport confirmed transporter function and identity of all cDNA clones was confirmed by restriction fragment mapping. GLUT1 and GLUT3 cDNA were further verified by polymerase chain reaction, DHA transport activity in both GLUT1 and GLUT3 was inhibited by 2-deoxyglucose, D-glucose, and S-O-methylglucose among other hexoses while fructose and L-glucose showed no inhibition, Inhibition by the endofacial inhibitor, cytochalasin B, was non-competitive and inhibition by the exofacial inhibitor, 4,6-O-ethylidene-alpha-glucose, was competitive. Expressed mutant constructs of GLUT1 and GLUT3 did not transport DHA. DHA and a-deoxyglucose uptake by Chinese hamster ovary cells overexpressing either GLUT1 or GLUT3 was increased 2-8 fold over control cells. These studies suggest GLUT1 and GLUT3 isoforms are the specific glucose transporter isoforms which mediate DHA transport and subsequent accumulation of AA. C1 NIDDK,NIH,MOL & CLIN NUTR SECT,BETHESDA,MD 20892. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. OI Burant, Charles/0000-0001-9189-5003 NR 67 TC 262 Z9 267 U1 3 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1997 VL 272 IS 30 BP 18982 EP 18989 DI 10.1074/jbc.272.30.18982 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XM342 UT WOS:A1997XM34200071 PM 9228080 ER PT J AU Stokoe, D Stephens, LR Copeland, T Gaffney, PRJ Reese, CB Painter, GF Holmes, AB McCormick, F Hawkins, PT AF Stokoe, D Stephens, LR Copeland, T Gaffney, PRJ Reese, CB Painter, GF Holmes, AB McCormick, F Hawkins, PT TI Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B SO SCIENCE LA English DT Article ID C-AKT; V-AKT AB Protein kinase B (PKB) is a proto-oncogene that is activated in signaling pathways initiated by phosphoinositide 3-kinase. Chromatographic separation of brain cytosol revealed a kinase activity that phosphorylated and activated PKB only in the presence of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P-3]. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P-3 was determined to have a dual role: its binding to the pleckstrin homology domain of PKB was required to allow phosphorylation by the upstream kinase and it directly activated the upstream kinase. C1 ONYX PHARMACEUT,RICHMOND,CA 94806. BABRAHAM INST,CAMBRIDGE CB2 4AT,ENGLAND. NCI,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV LONDON KINGS COLL,DEPT CHEM,LONDON WC2R 2LS,ENGLAND. UNIV CAMBRIDGE,DEPT CHEM,CAMBRIDGE CB2 3RA,ENGLAND. NR 23 TC 896 Z9 917 U1 1 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 25 PY 1997 VL 277 IS 5325 BP 567 EP 570 DI 10.1126/science.277.5325.567 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM867 UT WOS:A1997XM86700052 PM 9228007 ER PT J AU Kennedy, KA Stoll, BJ Ehrenkranz, RA Oh, W Wright, LL Stevenson, DK Lemons, JA Sowell, A Mele, L Tyson, JE Verter, J AF Kennedy, KA Stoll, BJ Ehrenkranz, RA Oh, W Wright, LL Stevenson, DK Lemons, JA Sowell, A Mele, L Tyson, JE Verter, J TI Vitamin A to prevent bronchopulmonary dysplasia in very-low-birth-weight infants: Has the dose been too low? SO EARLY HUMAN DEVELOPMENT LA English DT Article DE vitamin A; retinol; bronchopulmonary dysplasia; chronic lung disease ID RETINOL-BINDING PROTEIN; A SUPPLEMENTATION; ALPHA-TOCOPHEROL; PLASMA RETINOL; SERUM; PREMATURE; CAROTENE; ESTERS; LIVER; NUTRITION AB Objective: Inconsistent effects of vitamin A supplementation on prevention of bronchopulmonary dysplasia have been reported. Meta-analysis of these reports resulted in a relative risk of 0.69-1.02 for death or bronchopulmonary dysplasia associated with vitamin A supplementation. Effective dosage regimens or serum retinol concentrations have not been determined in previous reports. The purpose of this pilot study was to define a vitamin A regimen that produces serum retinol concentrations of 25-55 mu g/dl. Study design: In this three-phase study, 91 infants (mean birth weight 799-864 g) were enrolled. Vitamin A was administered three times/week for 4 weeks at an average daily dose of 986-2143 IU/day. Physical examinations were performed and serum retinol specimens were collected weekly to assess clinical signs of toxicity. Results: The majority of serum retinol concentrations remained < 25 mu g/dl until an intramuscular vitamin A dose of 5000 IU/dose three times/week was used. No clinical signs of toxicity were associated with the higher dosage and higher serum concentrations of vitamin A. Conclusion: A large clinical trial of vitamin A supplementation with 5000 IU/dose three times/week (25-114% more than the dose used in the three published clinical trials) is needed to assess whether vitamin A supplementation safely reduces the risk of bronchopulmonary dysplasia in very-low-birth-weight infants. (C) 1997 Elsevier Science Ireland Ltd. C1 EMORY UNIV,ATLANTA,GA 30322. YALE UNIV,NEW HAVEN,CT 06520. BROWN UNIV,WOMEN & INFANTS HOSP,PROVIDENCE,RI. NICHHD,BETHESDA,MD 20892. STANFORD UNIV,STANFORD,CA 94305. INDIANA UNIV,INDIANAPOLIS,IN 46204. CTR DIS CONTROL & PREVENT,ATLANTA,GA. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC 20052. RP Kennedy, KA (reprint author), UNIV TEXAS,SW MED CTR,DEPT PEDIAT,5323 HARRY HINES BLVD,E3 600,DALLAS,TX 75235, USA. FU NICHD NIH HHS [U10 HD27851, U10 HD21373, U10 HD27811] NR 30 TC 35 Z9 38 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD JUL 24 PY 1997 VL 49 IS 1 BP 19 EP 31 DI 10.1016/S0378-3782(97)01869-0 PG 13 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA XC438 UT WOS:A1997XC43800003 PM 9179535 ER PT J AU Goedert, JJ Steinmeyer, LA Nakatsuji, Y AF Goedert, JJ Steinmeyer, LA Nakatsuji, Y TI Hepatitis G infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HEMOPHILIACS; VIRUS C1 SHINSHU UNIV,MATSUMOTO,NAGANO 390,JAPAN. RP Goedert, JJ (reprint author), NCI,ROCKVILLE,MD 20852, USA. NR 5 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 JUL 24 PY 1997 VL 337 IS 4 BP 277 EP 277 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XL994 UT WOS:A1997XL99400014 PM 9229694 ER PT J AU Gorelick, DA AF Gorelick, DA TI Subpoenas and science SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Gorelick, DA (reprint author), NIDA,BALTIMORE,MD 21224, USA. 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 JUL 24 PY 1997 VL 337 IS 4 BP 282 EP 283 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XL994 UT WOS:A1997XL99400025 PM 9229701 ER PT J AU DeYoung, KL Ray, ME Su, YA Anzick, SL Johnstone, RW Trapani, JA Meltzer, PS Trent, JM AF DeYoung, KL Ray, ME Su, YA Anzick, SL Johnstone, RW Trapani, JA Meltzer, PS Trent, JM TI Cloning a novel member of the human interferon-inducible gene family associated with control of tumorigenicity in a model of human melanoma SO ONCOGENE LA English DT Article DE interferon-inducible; melanoma; tumorigenicity ID HUMAN-MALIGNANT MELANOMA; CHROMOSOME-6; IDENTIFICATION; CLUSTER; CELLS AB Chromosome 6-mediated suppression of tumorigenicity in malignant melanoma cell lines provides a model system to identify genes associated with the reversion of the tumorigenic phenotype. Using subtractive cDNA selection, we recently identified a series of novel genes which are differentially expressed in association with chromosome 6-mediated suppression. We now report the molecular characterization of a novel gene termed AIM2 for (Absent In Melanoma), which represents a 1485 bp cDNA. An open reading frame of 1032 base pairs, corresponding to 344 amino acid residues, is predicted. The predicted protein shares a conserved sequence domain of approximately 200 amino acids with known interferon-inducible genes of both human and mouse. We demonstrate that the AIM2 gene encodes a transcript of approximately 2 kb which is expressed in spleen, small intestine, and peripheral blood leukocytes. In addition, we have localized AIM2 to the long arm of human chromosome 1 (band q22) in a highly conserved region which also contains the known interferon-inducible genes IFI16 and MNDA. We have also demonstrated that, like IFI16 and MNDA, AIM2 is induced in HL60 cells by interferon gamma. Our findings support the existence of a family of genes in this region similar to the well-characterized mouse Ifi200 gene family. C1 NATL HUMAN GENOME RES INST,CANC GENET LAB,NIH,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. AUSTIN HOSP,AUSTIN RES INST,HEIDELBERG,VIC 3084,AUSTRALIA. NR 23 TC 122 Z9 131 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 24 PY 1997 VL 15 IS 4 BP 453 EP 457 DI 10.1038/sj.onc.1201206 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA XM238 UT WOS:A1997XM23800010 PM 9242382 ER PT J AU Ferrucci, L Guralnik, JM Corti, MC Pahor, M AF Ferrucci, L Guralnik, JM Corti, MC Pahor, M TI Dehydration, delirium, and disability in elderly patients - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 UNIV TENNESSEE,MEMPHIS,TN. RP Ferrucci, L (reprint author), NIA,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 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 JUL 23 PY 1997 VL 278 IS 4 BP 287 EP 288 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XL059 UT WOS:A1997XL05900016 ER PT J AU Burke, W Daly, M Garber, J Botkin, J Kahn, MJE Lynch, P McTiernan, A Offit, K Perlman, JA Petersen, G Thomson, E AF Burke, W Daly, M Garber, J Botkin, J Kahn, MJE Lynch, P McTiernan, A Offit, K Perlman, JA Petersen, G Thomson, E TI Benefits and risks of screening mammography in women with BRCA1 and BRCA2 mutations - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV UTAH,SALT LAKE CITY,UT. NATL BREAST CANC COALIT,RICHMOND,VA. UNIV TEXAS,HOUSTON,TX. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. MEM SLOAN KETTERING INST CANC RES,NEW YORK,NY. NCI,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD. NATL HUMAN GENOME RES INST,BETHESDA,MD. RP Burke, W (reprint author), UNIV WASHINGTON,SEATTLE,WA 98195, USA. NR 3 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 JUL 23 PY 1997 VL 278 IS 4 BP 290 EP 290 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XL059 UT WOS:A1997XL05900024 ER PT J AU Kaplan, JE Masur, H Jaffe, HW Holmes, KK AF Kaplan, JE Masur, H Jaffe, HW Holmes, KK TI Preventing opportunistic infections in persons infected with HIV: 1997 guidelines SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 CTR DIS CONTROL & PREVENT,NATL CTR HIV STD & TB PREVENT,ATLANTA,GA 30333. NIAID,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,CTR AIDS & STD,SEATTLE,WA 98195. RP Kaplan, JE (reprint author), CTR DIS CONTROL & PREVENT,DIV HIV AIDS PREVENT SURVEILLANCE & EPIDEMIOL,NATL CTR INFECT DIS,ATLANTA,GA 30333, USA. NR 21 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 JUL 23 PY 1997 VL 278 IS 4 BP 337 EP 338 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XL059 UT WOS:A1997XL05900038 PM 9228443 ER PT J AU Pak, CC Puri, A Blumenthal, R AF Pak, CC Puri, A Blumenthal, R TI Conformational changes and fusion activity of vesicular stomatitis virus glycoprotein: [I-125]iodonaphthyl azide photolabeling studies in biological membranes SO BIOCHEMISTRY LA English DT Article ID INFLUENZA-VIRUS; LOW-PH; PHOTOGENERATED REAGENTS; ENVELOPE GLYCOPROTEIN; CELL-MEMBRANES; HEMAGGLUTININ; ACTIVATION; PROTEINS; PEPTIDE; ANALOGS AB The interaction of VSV glycoprotein (VSV G) with biological membranes was studied by photosensitized labeling. The method is based on photosensitized activation by the fluorescent lipid analog 3,3'-dioctadecyloxacarbocyanine (DiO) of a hydrophobic probe, [I-125]iodonaphthyl azide ((125)INA), that rapidly partitions into the membrane bilayer of virus and cells. (125)INA labeling of proteins and lipids can be confined to the site of chromophore localization by photosensitized labeling. Photoactivation using visible Light of target membrane labeled with DiO and (125)INA, to which unlabeled virions are bound, results in exclusive labeling of envelope glycoproteins inserted into the target membrane [Pak et al. (1994) J. Biol. Chem. 263, 14614]. In this study, we labeled Lipid symmetric erythrocyte ghosts with (125)INA and DiO. Photosensitized activation of VSV prebound to labeled ghosts with visible light resulted in VSV G labeling under fusogenic conditions. Photoactivation of (125)INA by UV light, which is nonspecific, produced labeled VSV G at both acidic and neutral pH, Photosensitized labeling of VSV G by DiO-(125)INA-ghosts was also observed at pH 5.5, 4 degrees C, in the absence of mixing between viral and cellular lipids, suggesting insertion of the ectodomain of VSV G. Soluble VSV G lacking the transmembrane domain inserted into DiO-(125)INA-ghosts under the same conditions as intact VSV G. DiO inserted into intact VSV appeared to be a suitable fluorophore for continuous kinetic measurements of membrane fusion by fluorescence dequenching. Our photosensitized labeling results establish biochemical correlates for the three states of VSV G, which we had proposed based on kinetic data [Clague et al., Biochemistry 29, 1303]. in addition, we found that VSV G insertion into the target membrane is reversible, suggesting a ''velcro''-like attachment of the fusogenic domain with the target membrane. C1 NCI,FREDERICK CANC RES & DEV CTR,SECT MEMBRANE STRUCT & FUNCT,DIV BASIC SCI,FREDERICK,MD 21702. NR 48 TC 51 Z9 53 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 JUL 22 PY 1997 VL 36 IS 29 BP 8890 EP 8896 DI 10.1021/bi9702851 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XM538 UT WOS:A1997XM53800026 PM 9220976 ER PT J AU Hasenkrug, KJ Chesebro, B AF Hasenkrug, KJ Chesebro, B TI Immunity to retroviral infection: The Friend virus model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; T-CELL RESPONSIVENESS; LONG-TERM SURVIVOR; FBL-3 TUMOR-CELLS; PASSIVE IMMUNOTHERAPY; INDUCED IMMUNOSUPPRESSION; INDUCED ERYTHROLEUKEMIA; MONOCLONAL-ANTIBODIES; SPONTANEOUS-RECOVERY AB Friend virus infection of adult immunocompetent mice is a well established model for studying genetic resistance to infection by an immunosuppressive retrovirus, This paper reviews both the genetics of immune resistance and the types of immune responses required for recovery from infection, Specific major histocompatibility complex (MHC) class I and II alleles are necessary for recovery, as is a non-MHC gene, Rfv-3, which controls virus-specific antibody responses, In concordance with these genetic requirements are immunological requirements for cytotoxic T lymphocyte, T helper, and antibody responses, each of which provides essential nonoverlapping functions, The complexity of responses necessary for recovery from Friend virus infection has implications for both immunotherapies and vaccines, For example, it is shown that successful passive antibody therapy is dependent on MHC type because of the requirement for T cell responses, For vaccines, successful immunization requires priming of both T cell and B cell responses, In vivo depletion experiments demonstrate different requirements for CD8(+) T cells depending on the vaccine used, The implications of these studies for human retroviral diseases are discussed. RP Hasenkrug, KJ (reprint author), NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,NIH,HAMILTON,MT 59840, USA. NR 94 TC 84 Z9 84 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 1997 VL 94 IS 15 BP 7811 EP 7816 DI 10.1073/pnas.94.15.7811 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800019 PM 9223268 ER PT J AU Leapman, RD Gallant, PE Reese, TS Andrews, SB AF Leapman, RD Gallant, PE Reese, TS Andrews, SB TI Phosphorylation and subunit organization of axonal neurofilaments determined by scanning transmission electron microscopy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR DE electron energy loss spectroscopy; squid axon; intermediate filaments ID ENERGY-LOSS SPECTROSCOPY; EPIDERMAL KERATIN FILAMENTS; INTERMEDIATE FILAMENTS; LOSS SPECTRA; TAIL DOMAIN; ROD DOMAIN; PROTEIN; MASS; MICROANALYSIS; SPECTROMETER AB Phosphorylation plays a critical role in controlling the function of cytoskeletal assemblies but no direct method yet exists to measure the phosphorylation stale of proteins at the level of individual molecules and assemblies, Herein, we apply scanning transmission electron microscopy in combination with electron energy loss spectroscopy to measure the distributions of mass and phosphorus in neurofilaments (NFs) isolated from the squid giant: axon, We find that native squid NFs, in contrast to typical reconstituted intermediate filaments, are a relatively homogeneous population containing only eight coiled-foil dimers per cross section, The measured stoichiometry of similar to 1:1 for light/heavy peptides strongly suggests that squid NFs are composed oi heterodimers, Furthermore, each heavy chain of the dimers carries at least 100 phosphate groups and is, therefore, near-maximally phosphorylated. These results also demonstrate that scanning transmission electron microscopy combined with electron energy loss spectroscopy at the nanometer scale is capable of characterizing the level and distribution of phosphorylation in individual mass-mapped protein assemblies. C1 NINCDS,NEUROBIOL LAB,NIH,BETHESDA,MD 20892. RP Leapman, RD (reprint author), NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,NATL CTR RES RESOURCES,BLDG 13,ROOM 3N17,BETHESDA,MD 20892, USA. NR 36 TC 27 Z9 27 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 1997 VL 94 IS 15 BP 7820 EP 7824 DI 10.1073/pnas.94.15.7820 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800021 PM 9223270 ER PT J AU Buckbinder, L VelascoMiguel, S Chen, Y Xu, NZ Talbott, R Gelbert, L Gao, JZ Seizinger, BR Gutkind, JS Kley, N AF Buckbinder, L VelascoMiguel, S Chen, Y Xu, NZ Talbott, R Gelbert, L Gao, JZ Seizinger, BR Gutkind, JS Kley, N TI The p53 tumor suppressor targets a novel regulator of G protein signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR ID GENE; ACTIVATION; MUTATIONS; INDUCTION; ONCOGENES; CANCER; CELLS AB Heterotrimeric G proteins transduce multiple growth-factor-receptor-initiated and intracellular signals that may lead to activation of the mitogen-activated or stress-activated protein kinases, Herein we report on the identification of a novel p53 target gene (A28-RGS14) that is induced in response to genotoxic stress and encodes a novel member of a family of regulators of G protein signaling (RGS) proteins with proposed GTPase-activating protein activity. Overexpression of A28-RGS14p protein inhibits both G(i)- and G(q)-coupled growth-factor-receptor-mediated activation of the mitogen-activated protein kinase signaling pathway in mammalian cells. Thus, through the induction of A28-RGS14, p53 may regulate cellular sensitivity to growth and/or survival factors acting through G protein-coupled receptor pathways. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOL GENET,PRINCETON,NJ 08543. NIDR,MOL SIGNALING UNIT,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT BIOMOLEC DRUG DISCOVERY,PRINCETON,NJ 08543. RI Gutkind, J. Silvio/A-1053-2009 NR 24 TC 78 Z9 84 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 1997 VL 94 IS 15 BP 7868 EP 7872 DI 10.1073/pnas.94.15.7868 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800030 PM 9223279 ER PT J AU Dressman, HK Wang, CC Karam, JD Drake, JW AF Dressman, HK Wang, CC Karam, JD Drake, JW TI Retention of replication fidelity by a DNA polymerase functioning in a distantly related environment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR DE replication fidelity; DNA polymerase; bacteriophage T4; bacteriophage RB69 ID SPONTANEOUS MUTATION; EXONUCLEASE ACTIVITY; BACTERIOPHAGE-T4; INVITRO; ACCURACY; PROTEIN; MUTAGENESIS; SPECIFICITY; FREQUENCY; ABSENCE AB The primary structures of the replicative DNA polymerases (gp43s) of bacteriophage T4 and its distant phylogenetic relative RB69 are diverged, retaining only 61% identity and 74% similarity, Nevertheless, RB69 gp43 substitutes effectively for T4 gp43 in T4 DNA replication in vivo. We show here that RB69 gp43 replicates T4 genomes in vivo with a fidelity similar Co that achieved by T4 gp43. Furthermore, replication by RB69 gp43 in the distantly related environment does not enhance the mutator activities of mutations in T4 genes that encode other components of the multienzyme DNA replicase, We also show that the fidelities of RB69 gp43 and T4 gp43 are both high in vitro and that they are similarly and sharply reduced in vivo bg mutations that eliminate the 3'-exonucleolytic proofreading function, We conclude that gp43 interactions with the other replication proteins are probably nonessential for polymerase fidelity. C1 NIEHS, MOL GENET LAB, RES TRIANGLE PK, NC 27709 USA. TULANE UNIV, SCH MED, DEPT BIOCHEM, NEW ORLEANS, LA 70112 USA. FU NIGMS NIH HHS [GM54627, GM18842] NR 47 TC 24 Z9 25 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 1997 VL 94 IS 15 BP 8042 EP 8046 DI 10.1073/pnas.94.15.8042 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800062 PM 9223311 ER PT J AU Day, PM Yewdell, JW Porgador, A Germain, RN Bennink, JR AF Day, PM Yewdell, JW Porgador, A Germain, RN Bennink, JR TI Direct delivery of exogenous MHC class I molecule-binding oligopeptides to the endoplasmic reticulum of viable cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR ID RECEPTOR-MEDIATED ENDOCYTOSIS; TOXIC LYMPHOCYTES-T; BREFELDIN-A; ANTIGEN PRESENTATION; GOLGI PROTEINS; PEPTIDES; COMPLEX; BETA-2-MICROGLOBULIN; SEQUENCE; TAP AB After brief incubation of sells with fluorescein-conjugated peptides that bind major histocompatibility complex (MI-IC) class 1 molecules, peptides were detected within the endoplasmic reticulum (ER) by microscopy or by binding to radiolabeled class I molecules. ER delivery of a nonfluorescent peptide was demonstrated using a mAb highly specific for the peptide-class I molecule complex, ER localization of peptides: (i) required expression of appropriate class I molecules in the ER but not on the cell surface, (ii) was diminished by expression of TAP, the MHC-encoded cytosol to ER peptide transporter, and (iii) was blacked by pinocytosis inhibitors but not by brefeldin A. These findings demonstrate the existence of a pathway, likely vesicular in nature, that conveys small extracellular substances to the ER without traversing the Golgi complex or the cytosol. This pathway contributes to the loading of exogenous peptides to MHC class I molecules, but its evolutionary significance may lie in other cellular processes, such as maintaining ER homeostasis or signaling by extracellular substances. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 43 TC 82 Z9 82 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 1997 VL 94 IS 15 BP 8064 EP 8069 DI 10.1073/pnas.94.15.8064 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800066 PM 9223315 ER PT J AU Kwon, ED Hurwitz, AA Foster, BA Madias, C Feldhaus, AL Greenberg, NM Burg, MB Allison, JP AF Kwon, ED Hurwitz, AA Foster, BA Madias, C Feldhaus, AL Greenberg, NM Burg, MB Allison, JP TI Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR DE CTLA-4; B7.1; CD28; tumor rejection; cellular immunity ID CTLA-4; GENE; CD28 AB The identification of potentially useful immune-based treatments for prostate cancer has been severely constrained by the scarcity of relevant animal research models for this disease, Moreover, some of the most critical mechanisms involved in complete and proper antitumoral T cell activation have only recently been identified for experimental manipulation, namely, components involved in the costimulatory pathway for T cell activation, Thus, we have established a novel syngeneic murine prostate cancer model that permits us to examine two distinct manipulations intended to elicit an antiprostate cancer response through enhanced T cell costimulation: (i) provision of direct costimulation by prostate cancer cells transduced to express the B7.1 ligand and (ii) in vivo antibody-mediated blockade of the T cell CTLA-4, which prevents T cell down-regulation. In the present study we found that a tumorigenic prostate cancer cell line, TRAMPC1 (pTC1), derived from transgenic mice, is rejected by syngeneic C57BL/6 mice, but not athymic mice, after this cell line is transduced to express the costimulatory ligand B7.1, Also, we demonstrated that in vivo antibody-mediated blockade of CTLA-4 enhances antiprostate cancer immune responses, The response raised by anti-CTLA-4 administration ranges from marked reductions in wild-type pTC1 growth to complete rejection of these cells, Collectively, these experiments suggest that appropriate manipulation of T cell costimulatory and inhibitory signals may provide a fundamental and highly adaptable basis for prostate cancer immunotherapy, Additionally, the syngeneic murine model that we introduce provides a comprehensive system for further testing of immune-based treatments for prostate cancer. C1 UNIV CALIF BERKELEY,CANC RES LAB,BERKELEY,CA 94720. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,SCOTT DEPT UROL,HOUSTON,TX 77030. TARGETED GENET,SEATTLE,WA 98101. RP Kwon, ED (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,ROOM 1N105,BLDG 9,9 MEM DR,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA57986, CA64851, T32 CA009179, P50 CA058204, R01 CA064851, CA40041, R01 CA040041] NR 22 TC 234 Z9 240 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 1997 VL 94 IS 15 BP 8099 EP 8103 DI 10.1073/pnas.94.15.8099 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800072 PM 9223321 ER PT J AU Liu, YJ Hoffmann, A Grinberg, A Westphal, H McDonald, MP Miller, KM Crawley, JN Sandhoff, K Suzuki, K Proia, RL AF Liu, YJ Hoffmann, A Grinberg, A Westphal, H McDonald, MP Miller, KM Crawley, JN Sandhoff, K Suzuki, K Proia, RL TI Mouse model of G(M2) activator deficiency manifests cerebellar pathology and motor impairment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetics and the Origin of Species CY JAN 30-FEB 01, 1997 CL NATL ACAD SCIENCES BECKMAN CTR, IRVINE, CA SP Natl Acad Sciences HO NATL ACAD SCIENCES BECKMAN CTR DE animal model; G(M2) gangliosidosis; gene targeting; lysosomal storage disease ID TAY-SACHS-DISEASE; TARGETED DISRUPTION; HEXA GENE; PROTEIN; MICE; MUTATION AB The G(M2) activator deficiency (also known as the AB variant), Tay-Sachs disease, and Sandhoff disease are the major forms of the G(M2) gangliosidoses, disorders caused by defective degradation of G(M2) ganglioside. Tay-Sachs and Sandhoff diseases are caused by mutations in the genes (HEXA and HEXB) encoding the subunits of beta-hexosaminidase A. The G(M2) activator deficiency is caused by mutations in the GM2A gene encoding the G(M2) activator protein, For degradation of G(M2) ganglioside by beta-hexosamindase A, the G(M2) activator protein must participate by forming a soluble complex with the ganglioside, In each of the disorders, G(M2) ganglioside and related lipids accumulate to pathologic levels in neuronal lysosomes, resulting in clinically similar disorders with an onset in the first year of life, progressive neurodegeneration, and death by early childhood, We previously have described mouse models of Tay-Sachs (Hexa -/-) and Sandhoff (Hexb -/-) diseases with vastly different clinical phenotypes. The Hexa -/- mice were asymptomatic whereas the Hexb -/- mice were severely affected. Through gene disruption in embryonic stem cells we now have established a mouse model of the G(M2) activator deficiency that manifests an intermediate phenotype. The Gm2a -/- mice demonstrated neuronal storage but only in restricted regions of the brain (piriform, entorhinal cortex, amygdala, and hypothalamic nuclei) reminiscent of the asymptomatic Tay-Sachs model mice, However, unlike the Tay-Sachs mice, the Gm2a -/- mice displayed significant storage in the cerebellum and defects in balance and coordination, The abnormal ganglioside storage in the Gm2a -/- mice consisted of G(M2) with a low amount of G(A2). The results demonstrate that the activator protein is required for G(M2) degradation and also may indicate a role for the G(M2) activator in G(A2) degradation. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NIMH,SECT BEHAV NEUROPHARMACOL,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. UNIV BONN,INST ORGAN CHEM & BIOCHEM,D-53121 BONN,GERMANY. UNIV N CAROLINA,CTR NEUROSCI,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PATHOL & LAB MED,CHAPEL HILL,NC 27599. RP Liu, YJ (reprint author), NIDDKD,SECT BIOCHEM GENET,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892, USA. RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [P30 HD003110, P30-HD 03110]; NINDS NIH HHS [R01 NS024453, R01-NS 24453] NR 13 TC 63 Z9 64 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 1997 VL 94 IS 15 BP 8138 EP 8143 DI 10.1073/pnas.94.15.8138 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XM428 UT WOS:A1997XM42800079 PM 9223328 ER PT J AU Carlyle, JR Michie, AM Furlonger, C Nakano, T Lenardo, MJ Paige, CJ ZunigaPflucker, JC AF Carlyle, JR Michie, AM Furlonger, C Nakano, T Lenardo, MJ Paige, CJ ZunigaPflucker, JC TI Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; HEMATOPOIETIC STEM-CELLS; HUMAN T-CELLS; C-KIT; FETAL THYMOCYTES; B-CELLS; DENDRITIC CELLS; MURINE THYMUS; BONE-MARROW; EXPRESSION AB Bipotent progenitors for T and natural killer (NK) lymphocytes are thought to exist among early precursor thymocytes. The identification and functional properties of such a progenitor population remain undefined. We report the identification of a novel developmental stage during fetal thymic ontogeny that delineates a population of T/NK-committed progenitors (NK1.1(+)/CD117(+)/CD44(+)/CD25(-)). Thymocytes at this stage in development are phenotypically and functionally distinguishable from the pool of multipotent lymphoid-restricted (B, T, and NK) precursor thymocytes. Exposure of multipotent precursor thymocytes or fetal liver-derived hematopoietic progenitors to thymic stroma induces differentiation to the bipotent developmental stage. Continued exposure to a thymic microenvironment results in predominant commitment to the T cell lineage, whereas coculture with a bone marrow-derived stromal cell line results in the generation of mature NK cells. Thus, the restriction point to T and NK lymphocyte destinies from a multipotent progenitor stage is marked by a thymus-induced differentiation step. C1 UNIV TORONTO,DEPT IMMUNOL,TORONTO,ON M5S 1A8,CANADA. UNIV TORONTO,WELLESLEY HOSP,RES INST,TORONTO,ON M4Y 1J3,CANADA. OSAKA UNIV,MICROBIAL DIS RES INST,DEPT MOL CELL BIOL,SUITA,OSAKA 565,JAPAN. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI Zuniga-Pflucker, Juan/H-1295-2012; OI Zuniga-Pflucker, Juan Carlos/0000-0003-2538-3178 NR 45 TC 111 Z9 113 U1 0 U2 3 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 JUL 21 PY 1997 VL 186 IS 2 BP 173 EP 182 DI 10.1084/jem.186.2.173 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XM669 UT WOS:A1997XM66900001 PM 9221746 ER PT J AU Boesteanu, A DeSilva, AD Nakajima, H Leonard, WJ Peschon, JJ Joyce, S AF Boesteanu, A DeSilva, AD Nakajima, H Leonard, WJ Peschon, JJ Joyce, S TI Distinct roles for signals relayed through the common cytokine receptor gamma chain and interleukin 7 receptor alpha chain in natural T cell development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PROMPTLY PRODUCE INTERLEUKIN-4; CLASS-I MOLECULES; IL-2 RECEPTOR; BETA-CHAIN; RECEPTOR-ALPHA/BETA(+) CELLS; DEFICIENT MICE; EXPRESSION; COMPLEX; EXPANSION; SUBSET AB The commitment, differentiation, and expansion of mainstream alpha/beta T cells during ontogeny depend on the highly controlled interplay of signals relayed by cytokines through their receptors on progenitor cells. The role of cytokines in the development of natural killer (NK)1(+) natural T cells is less clearly understood. In an approach to define the role of cytokines in the commitment, differentiation, and expansion of NK1(+) T cells, their development was studied in common cytokine receptor gamma chain (gamma c) and interleukin (IL)-7 receptor alpha (IL-7R alpha)-deficient mice. These mutations block mainstream alpha/beta T cell ontogeny at an early prethymocyte stage. Natural T cells do not develop in gamma c-deficient mice; they are absent in the thymus and peripheral lymphoid organs such as the liver and the spleen. In contrast, NK1(+) T cells develop in IL-7R alpha-deficient mice in the thymus, and they are present in the liver and in the spleen. However, the absolute number of NK1(+) T cells in the thymus of IL-7R alpha-deficient mice is reduced to similar to 10%, compared to natural T cell number in the wild-type thymus. Additional data revealed that NK1(+) T cell ontogeny is not impaired in IL-2- or IL-4-deficient mice, suggesting that neither IL-2, IL-4, nor IL-7 are required for their development. From these data, we conclude that commitment and/or differentiation to the NK1(+) natural T cell lineage requires signal transduction through the gamma c, and once committed, their expansion requires signals relayed through the IL-7R alpha. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA 17033. NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. FU NHLBI NIH HHS [R01 HL54977, R01 HL054977] NR 37 TC 37 Z9 37 U1 0 U2 1 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 JUL 21 PY 1997 VL 186 IS 2 BP 331 EP 336 DI 10.1084/jem.186.2.331 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA XM669 UT WOS:A1997XM66900018 PM 9221763 ER PT J AU Colaianni, LA AF Colaianni, LA TI An intractable error in MEDLINE - Comment SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Letter RP Colaianni, LA (reprint author), NATL LIB MED,LIB OPERAT,BETHESDA,MD 20894, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AUSTRALASIAN MED PUBL CO LTD PI SYDNEY PA LEVEL 1, 76 BERRY ST, SYDNEY NSW 2060, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD JUL 21 PY 1997 VL 167 IS 2 BP 111 EP 112 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XM763 UT WOS:A1997XM76300023 ER PT J AU Durbin, AP Siew, JW Murphy, BR Collins, PL AF Durbin, AP Siew, JW Murphy, BR Collins, PL TI Minimum protein requirements for transcription and RNA replication of a minigenome of human parainfluenza virus type 3 and evaluation of the rule of six SO VIROLOGY LA English DT Article ID MESSENGER-RNA; SENDAI VIRUS; VACCINIA VIRUS; SYNTHETIC ANALOGS; EXPRESSION SYSTEM; PARA-INFLUENZA; REPORTER GENE; P-GENE; SEQUENCE; RESCUE AB A reconstituted transcription and RNA replication system for human parainfluenza virus type 3 (HPIV3) was developed using components expressed intracellularly from transfected plasmids driven by T7 RNA polymerase supplied by a vaccinia virus recombinant The system is based on a negative-sense analog of HPIV3 genomic RNA in which the viral genes were deleted and replaced with that encoding bacterial chloramphenicol acetyl transferase (CAT). The N, P, and L proteins expressed from cotransfected plasmids were necessary and sufficient to direct efficient transcription and RNA replication. Transcription yielded subgenomic polyadenylated mRNA, which was isolated by oligo(dT) chromatography. RNA replication yielded a mini-antigenome and progeny minigenome, which were shown to be encapsidated based on resistance to digestion with micrococcal nuclease. A panel of cDNAs was constructed to encode minigenomes which differed in length by single-nucleotide increments. Transcription and RNA replication in the reconstituted system were most efficient for the minigenome whose length was an even multiple of six. Both RNA replication and transcription appeared to be governed by the rule. However, minigenomes whose lengths were one nucleotide greater than or less than an even multiple of six also were very active, especially in RNA replication, indicating that the rule was not absolute. (C) 1997 Academic Press. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 36 TC 62 Z9 67 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 21 PY 1997 VL 234 IS 1 BP 74 EP 83 DI 10.1006/viro.1997.8633 PG 10 WC Virology SC Virology GA XN039 UT WOS:A1997XN03900007 PM 9234948 ER PT J AU Shakil, AO Hadziyannis, S Hoofnagle, JH DiBisceglie, AM Gerin, JL Casey, JL AF Shakil, AO Hadziyannis, S Hoofnagle, JH DiBisceglie, AM Gerin, JL Casey, JL TI Geographic distribution and genetic variability of hepatitis delta virus genotype I SO VIROLOGY LA English DT Article ID EVOLUTIONARY TREES; MOLECULAR-CLONING; RNA; ANTIGEN; SERUM; PARTICLES; SEQUENCES; OCCURS; AGENT AB Three genotypes of hepatitis delta virus (HDV) have been identified, each with different geographic distributions and disease associations. To better define the geographic distribution and genetic variability of HDV genotype I, and to evaluate the extent of genome variability in populations with different patterns of HDV infection, we have analyzed the sequence of Nov RNA in the sera of 72 patients from different areas. Patients were primarily residents of the United States and areas in and around Greece, including Archangelos, Rhodes. All sequences obtained belonged to HDV genotype I, confirming the wide geographic distribution of this genotype and its predominance in Europe and the United States. In contrast to previous studies, phylogenetic analysis of this large and diverse group of sequences, along with all available previously published HDV sequences, showed no well-defined subtypes within genotype I. Low sequence diversity was found for isolates from the United States, Archangelos, Turkey, and Albania, suggesting that HDV was introduced more recently and/or from fewer sources into these areas as compared to mainland Greece, Italy, and north Africa, where sequence diversity is much greater. The low sequence diversity among isolates from Archangelos is particularly interesting in light of the unusually mild pattern of HDV disease found in this community. Comparison of nucleic acid and amino acid sequences within and among genotypes indicated both highly conserved regions as well as genotype-specific sequences that could be related to functional differences. The most distinctive of the latter was that corresponding to the C-terminal 19-20 amino acids of the long form of hepatitis delta antigen, which is highly conserved within each genotype but considerably diverged among them. (C) 1997 Academic Press. C1 GEORGETOWN UNIV,MED CTR,DIV MOL VIROL & IMMUNOL,ROCKVILLE,MD. NIDDKD,NIH,BETHESDA,MD 20892. UNIV ATHENS,SCH MED,DEPT MED 2,GR-11527 ATHENS,GREECE. FU NIAID NIH HHS [N01-AI-45179] NR 41 TC 70 Z9 74 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 21 PY 1997 VL 234 IS 1 BP 160 EP 167 DI 10.1006/viro.1997.8644 PG 8 WC Virology SC Virology GA XN039 UT WOS:A1997XN03900016 PM 9234957 ER PT J AU Fraser, JK Sugarman, J McCurdy, PR Martin, NL Ammann, AJ AF Fraser, JK Sugarman, J McCurdy, PR Martin, NL Ammann, AJ TI Scientific, logistical, and ethical issues related to creation of a stem cell repository for use in experimental trials of gene therapy for AIDS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material ID UMBILICAL-CORD-BLOOD; PLACENTAL BLOOD; TRANSPLANTATION; MOUSE C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED HEMATOL ONCOL,LOS ANGELES,CA 90095. JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90095. DUKE UNIV,MED CTR,DURHAM,NC 27710. NHLBI,BETHESDA,MD 20892. PEDIAT AIDS FDN,SANTA MONICA,CA 90404. AMER FDN AIDS RES,SAN RAFAEL,CA 94901. AMER FDN AIDS RES,NEW YORK,NY. US FDA,ROCKVILLE,MD 20857. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. AMER RED CROSS,CAROLINAS BLOOD BANK,CHARLOTTE,NC. RI Fraser, John/I-7309-2013 NR 16 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 20 PY 1997 VL 13 IS 11 BP 905 EP 907 DI 10.1089/aid.1997.13.905 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XK471 UT WOS:A1997XK47100001 PM 9223405 ER PT J AU Reimann, KA Lin, WY Bixler, S Browning, B Ehrenfels, BN Lucci, J Miatkowski, K Olson, D Parish, TH Rosa, MD Oleson, FB Hsu, YM Padlan, EA Letvin, NL Burkly, LC AF Reimann, KA Lin, WY Bixler, S Browning, B Ehrenfels, BN Lucci, J Miatkowski, K Olson, D Parish, TH Rosa, MD Oleson, FB Hsu, YM Padlan, EA Letvin, NL Burkly, LC TI A humanized form of a CD4-specific monoclonal antibody exhibits decreased antigenicity and prolonged plasma half-life in rhesus monkeys while retaining its unique biological and antiviral properties SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; ANTI-CD4 ANTIBODY; CD4 DOMAIN-2; T4 MOLECULE; CELL-FUSION; INFECTION; INHIBITION; RESPONSES; RECEPTOR AB Certain monoclonal antibodies (MAbs) directed against CD4 can efficiently block HIV-1 replication in vitro, To explore CD4-directed passive immunotherapy for prevention or treatment of AIDS virus infection, we previously examined the biological activity of a nondepleting CD4-specific murine MAb, mu5A8, This MAb, specific for domain 2 of CD4, blocks HIV-1 replication at a post-gp120-CD4 binding step, When administered to normal rhesus monkeys, all CD4(+) target cells were coated with antibody, yet no cell clearance or measurable immunosuppression occurred, However, strong anti-mouse Ig responses rapidly developed in all monkeys, In the present study, we report a successfully humanized form of mu5A8 (hu5A8) that retains binding to both human and monkey CD4 and anti-AIDS virus activity, When administered intravenously to normal rhesus monkeys, hu5A8 bound to all target CD4(+) cells without depletion and showed a significantly longer plasma half-life than mu5A8, Nevertheless, an anti-hu5AS response directed predominantly against V region determinants did eventually appear within 2 to 4 weeks in most animals, However, when hu5A8 was administered to rhesus monkeys chronically infected with the simian immunodeficiency virus of macaques, anti-hu5AS antibodies were not detected, Repeated administration of hu5A8 in these animals resulted in sustained plasma levels and CD4(+) cell coating with humanized antibody for 6 weeks, These studies demonstrate the feasibility of chronic administration of CD4-specific MAb as a potential means of treating or preventing HIV-1 infection. C1 BIOGEN INC,CAMBRIDGE,MA 02142. NIDDKD,MOL BIOL LAB,NIH,BETHESDA,MD 20892. RP Reimann, KA (reprint author), HARVARD UNIV,DIV VIRAL PATHOGENESIS,BETH ISRAEL DEACONESS MED CTR,DEPT MED,SCH MED,RE-113,BOSTON,MA 02215, USA. FU NCRR NIH HHS [RR00055, RR00168] NR 41 TC 49 Z9 51 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 20 PY 1997 VL 13 IS 11 BP 933 EP 943 DI 10.1089/aid.1997.13.933 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XK471 UT WOS:A1997XK47100005 PM 9223409 ER PT J AU Tsai, WP Rimelzwaan, GF Merges, MJ Wu, SC Conley, S Kung, HF Garrity, R Goudsmit, J Nara, PL AF Tsai, WP Rimelzwaan, GF Merges, MJ Wu, SC Conley, S Kung, HF Garrity, R Goudsmit, J Nara, PL TI Preliminary findings of an in vitro human spleen mononuclear cell culture system for primary isolates of HIV type 1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN KUPFFER CELLS; CAPILLARY ENDOTHELIAL-CELLS; POLYMERASE CHAIN-REACTION; MESSENGER-RNA EXPRESSION; INFECTIOUS-ANEMIA VIRUS; T-CELLS; RHESUS MACAQUES; VIRAL BURDEN; DISEASE PROGRESSION AB Acute HIV-1 infection is often manifested with a high level of viremia, The cell types and tissues/organs that contribute to the virus load are thought to be of central and peripheral lymphoreticular origin, The establishment and permissiveness of organ-based cell culture systems from spleen with laboratory strains or primary isolates of HIV-1 have not been reported, We studied unseparated splenic mononuclear cells (SMCs) and adherent cells derived from human spleen and liver in comparison with blood monocyte-derived macrophages (MDMs), Unstimulated, SMCs were highly permissive to primary lymphotropic HIV-1 and dual/macrophage-tropic isolates (which are able to replicate in both MDMs and PBMCs). Furthermore, SMCs were found to replicate virus to high titer in a rapid log-phase manner and exhibited a prolonged stationary phase of virus production, unlike PBMCs, which required conventional activation with mitogens and exhibited a much shorter period of virus production, Interestingly, the SMCs maintained themselves as a mixed phenotype of nested lymphocytes with complex and well-differentiated macrophage(s) for extended periods of time, In addition, splenic macrophages readily purified by adherence were highly permissive to a dual/macrophage-tropic primary isolate, HIV-1(ADA), intermediate with two laboratory strains, HIV-1(RF) and HIV-1(HXB3), and least permissive to the lymphotropic primary isolate HIV-1(Mr452) and two other laboratory strains, HIV-1(CC) and HIV-1(MN). The replication of HIV-1(ADA) as measured by extracellular p24 was sustained for up to 7 weeks and similar to the replication patterns observed with adherent hepatic macrophages and blood-derived MDMs, This study demonstrates that exogenous stimulation is not required for infection of these cells; either adherence-isolated and/or mixed lymphoid populations can be studied together, and viable stocks can be readily prepared and cryopreserved, In addition, these cells could be used for isolating new and/or other variants of HIV-1. Thus, the use of the SMC primary in vitro cell culture system for future studies involving HIV-1 is warranted. C1 NCI,FREDERICK CANC RES & DEV CTR,VACCINE RESISTANT DIS SECT,DIRECTORS LAB,OFF DIRECTOR,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,DIV BASIC SCI,FREDERICK,MD 21702. ACAD MED CTR,HUMAN RETROVIRUS LAB,DEPT VIROL,AMSTERDAM,NETHERLANDS. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. SCI APPLICAT INT CORP,FREDERICK,MD 21702. NR 78 TC 3 Z9 3 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 JUL 20 PY 1997 VL 13 IS 11 BP 967 EP 977 DI 10.1089/aid.1997.13.967 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XK471 UT WOS:A1997XK47100009 PM 9223413 ER PT J AU Hanazono, Y Yu, JM Dunbar, CE Emmons, RVB AF Hanazono, Y Yu, JM Dunbar, CE Emmons, RVB TI Green fluorescent protein retroviral vectors: Low titer and high recombination frequency suggest a selective disadvantage SO HUMAN GENE THERAPY LA English DT Article ID MAMMALIAN-CELLS; GENE-TRANSFER; EXPRESSION; MARKER AB Green fluorescent protein (GFP) has been used as a reporter molecule for gene expression because it fluoresces green after blue-light excitation. Inclusion of this gene in a vector could allow rapid, nontoxic selection of successfully transduced cells, However, many attempts by our laboratory to isolate stable retroviral producer cell clones secreting biologically active vectors containing either the highly fluorescent S65T-GFP mutant or humanized GFP have failed. Vector plasmids containing various forms of GFP and the neomycin resistance gene were transfected into three different packaging cell lines and fluorescence was observed for several days, but stable clones selected with G418 no longer fluoresced. Using confocal microscopy, the brightest cells were observed to contract and die within a matter of days. RNA slot-blot analysis of retroviral producer supernatants showed no viral production from the GFP plasmid-transfected clones, although all clones derived after transfection with an identical retroviral construct not containing GFP produced virus. Genomic Southern analysis of the GFP-transduced clones showed a much higher probability of rearrangement of the priviral sequences than in the control non-GFP clones. Overall, 18/34 S65T-GFP clones and 17/33 humanized-GFP clones had rearrangements, whereas 2/15 control non-GFP clones had rearrangements. Hence, producer cells expressing high levels of these GFP genes seem to be selected against, with stable clones undergoing major rearrangements or other mutations that both abrogate GFP expression and prevent vector production. These observations indicate that GFP may not be an appropriate reporter gene for gene transfer applications in our vector/packaging system. C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 18 TC 91 Z9 100 U1 1 U2 5 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 JUL 20 PY 1997 VL 8 IS 11 BP 1313 EP 1319 DI 10.1089/hum.1997.8.11-1313 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA XT345 UT WOS:A1997XT34500002 PM 9295126 ER PT J AU Pettitt, DJ Forman, MR Hanson, RL Knowler, WC Bennett, PH AF Pettitt, DJ Forman, MR Hanson, RL Knowler, WC Bennett, PH TI Breastfeeding and incidence of non-insulin-dependent diabetes mellitus in Pima Indians SO LANCET LA English DT Article ID FORMULA-FED INFANTS; 1ST YEAR; BREAST; MILK; LIFE AB Background Early exposure to cow's milk has been implicated in the occurrence of insulin-dependent diabetes mellitus but there is little information about infant-feeding practices and subsequent non-insulin-dependent diabetes mellitus (NIDDM). We examined the association between breastfeeding and NIDDM in a population with a high prevalence of this disorder, the Pima Indians. Methods Glucose-tolerance status was obtained from a 75 g oral glucose-tolerance test. A standard questionnaire given to mothers was used to classify infant-feeding practices for the first 2 months of life into three groups; exclusively breastfed, some breastfeeding, or exclusively bottlefed. The association between the three infant-feeding groups and NIDDM was analysed by multiple logistic regression. Findings Data were available for 720 Pima Indians aged between 10 and 39 years. 325 people who were Background Early exposure to cow's milk has been implicated in the occurrence of insulin-dependent diabetes mellitus but there is little information about infant-feeding practices and subsequent non-insulin-dependent diabetes mellitus (NIDDM). We examined the association between breastfeeding and NIDDM in a population with a high prevalence of this disorder, the Pima Indians. Methods Glucose-tolerance exclusively bottlefed had significantly higher age-adjusted and sex-adjusted mean relative weights (146%) than 144 people who were exclusively breastfed (140%) or 251 people who had some breastfeeding (139%) (p=0.019), People who were exclusively breastfed had significantly lower rates of NIDDM than those who were exclusively bottlefed in ail age-groups (age 10-19, 0 of 56 vs 6 [3.6%] of 165; age 20-29, 5 [8.6%] of 58 vs 17 [14.7%] of 116]; age 30-39, 6 [20.0%] of 30 vs 13 [29.6%] of 44). The odds ratio for NIDDM in exclusively breastfed people, compared with those exclusively bottlefed, was 0.41 (95% CI 0.18-0.93) adjusted for age, sex, birthdate, parental diabetes, and birthweight. Interpretation Exclusive breastfeeding for the first 2 months of life is associated with a significantly lower rate of NIDDM in Pima Indians. The increase in prevalence of diabetes in some populations may be due to the concomitant decrease in breastfeeding. C1 NIDDK,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ 85014. NATL CANC INST,CANC PREVENT STUDIES BRANCH,BETHESDA,MD. RP Pettitt, DJ (reprint author), NIDDK,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ 85014, USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 34 TC 156 Z9 158 U1 0 U2 5 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 19 PY 1997 VL 350 IS 9072 BP 166 EP 168 DI 10.1016/S0140-6736(96)12103-6 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA XL722 UT WOS:A1997XL72200010 PM 9250183 ER PT J AU Cervenakova, L Rohwer, R Williams, ES Brown, P Gajdusek, DC AF Cervenakova, L Rohwer, R Williams, ES Brown, P Gajdusek, DC TI High sequence homology of the PrP gene in mule deer and Rocky Mountain elk SO LANCET LA English DT Letter C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892. VET ADM MED CTR,MOL NEUROVIROL UNIT,BALTIMORE,MD. UNIV WYOMING,DEPT VET SCI,LARAMIE,WY 82071. NR 5 TC 10 Z9 12 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 19 PY 1997 VL 350 IS 9072 BP 219 EP 220 DI 10.1016/S0140-6736(05)62387-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XL722 UT WOS:A1997XL72200057 PM 9250209 ER PT J AU Gubin, AN Reddy, B Njoroge, JM Miller, JL AF Gubin, AN Reddy, B Njoroge, JM Miller, JL TI Long-term, stable expression of green fluorescent protein in mammalian cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article AB Despite the proven utility of green fluorescent protein (GFP) as a reporter molecule for transient gene expression, the adequacy of this marker for models requiring durable, high-level gene expression has not been fully tested. To address this issue, we performed the transfection of Chinese Hamster Ovary (CHO) cells with plasmid DNA encoding both GFP and neomycin phosphotransferase (neo) cassettes. The expression of GFP was measured after the cells were cultured in the presence or absence of G418-mediated selective pressure. After removal of G418 from the growth medium, the percentage of pooled G418 resistant transfectants which co-expressed the GFP transgene increased or remained unchanged. Flow cytometric and visual isolation of GFP-expressing cells was possible without continued selection in G418, One cloned cell line, C463, maintained high-level green fluorescence for 18 weeks in G418 and an additional 12 weeks in nonselective medium. Our data suggest expression of GFP does not confer a growth disadvantage in mammalian cells, (C) 1997 Academic Press. C1 NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NR 14 TC 46 Z9 73 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 18 PY 1997 VL 236 IS 2 BP 347 EP 350 DI 10.1006/bbrc.1997.6963 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XM955 UT WOS:A1997XM95500024 PM 9240438 ER PT J AU Conner, EA Wirth, PJ Kiss, A SantoniRugiu, E Thorgeirsson, SS AF Conner, EA Wirth, PJ Kiss, A SantoniRugiu, E Thorgeirsson, SS TI Growth inhibition and induction of apoptosis by HGF in transformed rat liver epithelial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEPATOCELLULAR-CARCINOMA CELLS; C-MYC; PROTEIN; RECEPTOR; PROLIFERATION; FIBROBLASTS; ONCOGENE; CLONING; HEPATOCYTES; TUMORS AB Recently we demonstrated in a transgenic mouse model that hepatocyte growth factor (HGF) inhibits c-myc dependent hepatocarcinogenesis. The inhibitory effects of HGF in carcinogenesis were further characterized using a series of rat liver epithelial (RLE) cell lines which were transformed in vitro with either aflatoxin or oncogenes, or spontaneously. HGF caused a cytostatic effect and enhanced cell motility in spontaneously and aflatoxin-transformed cells. In normal RLE cells HGF was slightly stimulatory and did not induce scattering, The HGF receptor was tyrosine phosphorylated in all cell lines, indicating that it is functionally active and capable of signaling events. In the aflatoxin transformed cells HGF also induced apoptosis, associated with constitutive c-myc expression and 1 Kb bax-alpha transcripts. These findings indicate that transformed RLE cell lines may provide a useful model to further examine the mechanism(s) by which HGF and its receptor modulate neoplastic development. (C) 1997 Academic Press. C1 NCI, EXPT CARCINOGENESIS LAB, DIV BASIC SCI, BETHESDA, MD 20892 USA. NR 37 TC 39 Z9 39 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 18 PY 1997 VL 236 IS 2 BP 396 EP 401 DI 10.1006/bbrc.1997.6938 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XM955 UT WOS:A1997XM95500034 PM 9240448 ER PT J AU Clair, T Krutzsch, HC Liotta, LA Stracke, ML AF Clair, T Krutzsch, HC Liotta, LA Stracke, ML TI Nucleotide binding to autotaxin: Crosslinking of bound substrate followed by lysC digestion identifies two labeled peptides SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MOTILITY-STIMULATING PROTEIN; MOLECULAR-CLONING; CDNA CLONING; ADENOSINE; PHOSPHODIESTERASE; PC-1; DIFFERENTIATION; PURIFICATION; GENERATION; MEMBRANES AB Autotaxin (ATX) is a 125 kDa glycoprotein motility factor and exoenzyme which can catalyze the hydrolysis of either the alpha-beta or at the beta-gamma phosphodiester bond in ATP. Its motility stimulating activity requires an intact 5'-nucleotide phosphodiesterase (PDE) active site, Photolysis-dependent labeling of ATX with alpha[P-32]-8-N-3-ATP, lysC digestion, and peptide HPLC resolved two radioactive fractions containing single peptides whose amino-terminal sequences were determined. Peptide A (T(210)FPNLYTLATG...) was derived from the PDE active site and peptide B (Y(318)GPFGPEMTNP...) was not previously known to be involved in any of the activities of ATX. The differential effect of NaCl concentration on the labeling of these two peptides, as well as on the two reaction types catalyzed by ATX, allows a classification of activities which predicts both the position of preferential peptide labeling by bound ATP and also the position of phosphodiester bond hydrolysis. (C) 1997 Academic Press. RP Clair, T (reprint author), NCI,PATHOL LAB,DIV CLIN SCI,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 32 TC 9 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 18 PY 1997 VL 236 IS 2 BP 449 EP 454 DI 10.1006/bbrc.1997.6982 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XM955 UT WOS:A1997XM95500045 PM 9240459 ER PT J AU Shick, KA Xavier, KA Rajpal, A SmithGill, SJ Willson, RC AF Shick, KA Xavier, KA Rajpal, A SmithGill, SJ Willson, RC TI Association of the anti-hen egg lysozyme antibody HyHEL-5 with avian species variant and mutant lysozymes SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE molecular recognition; enthalpy; antibody; lysozyme; calorimetry ID 3-DIMENSIONAL STRUCTURE; ANTILYSOZYME ANTIBODIES; MONOCLONAL-ANTIBODY; PROTEIN ANTIGEN; REACTIVE SITE; BINDING; COMPLEX; THERMODYNAMICS; RESIDUES; TRYPSIN AB The energetics of association of the murine anti-hen egg lysozyme antibody HyHEL-5 with bobwhite quail lysozyme, California quail lysozyme, and the Arg45 --> Lys mutant of hen egg lysozyme was characterized by isothermal titration calorimetry. The association of each lysozyme with HyHEL-5 is enthalpically driven in the temperature range 10 degrees C to 37 degrees C. The calorimetric results indicate that the salt-links between Arg45 and Arg68 of hen egg lysozyme and GluH50 on the HyHEL-5 paratope are energetically important in HyHEL-5/HEL association. In contrast to previous studies, the results suggest that the three characteristic 'quail' mutations affect the energetics of antibody/antigen association, even though they are buried and not in direct contact with the antibody. (C) 1997 Published by Elsevier Science B.V. C1 UNIV HOUSTON,DEPT CHEM ENGN,HOUSTON,TX 77204. TANOX BIOSYST INC,HOUSTON,TX 77025. JOHNS HOPKINS UNIV,DEPT CHEM,BALTIMORE,MD 21218. UNIV CALIF BERKELEY,DEPT CHEM,BERKELEY,CA 94720. NCI,GENET LAB,NIH,BETHESDA,MD 20892. UNIV HOUSTON,DEPT BIOCHEM & BIOPHYS SCI,HOUSTON,TX 77204. FU NIGMS NIH HHS [GM44344] NR 46 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD JUL 18 PY 1997 VL 1340 IS 2 BP 205 EP 214 DI 10.1016/S0167-4838(97)00035-6 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XM216 UT WOS:A1997XM21600005 PM 9252107 ER PT J AU Wood, GK Lipska, BK Weinberger, DR AF Wood, GK Lipska, BK Weinberger, DR TI Behavioral changes in rats with early ventral hippocampal damage vary with age at damage SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE neonatal lesion; hippocampus; ibotenic acid; stereotypy; amphetamine; apomorphine; dopamine ID HALOPERIDOL-INDUCED CATALEPSY; INDUCED STEREOTYPIC BEHAVIORS; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; CORTICAL-LESIONS; ANIMAL-MODEL; SCHIZOPHRENIA; 6-HYDROXYDOPAMINE; DOPAMINE; ADULT AB Our previous work demonstrated that neonatal (on postnatal day 7, PD7) excitotoxic damage of the ventral hippocampus (VH) results in delayed emergence of behaviors related to dopaminergic (DA) transmission. In this study, the developmental effects of VH lesions induced at two other ages were investigated in the rat. Ibotenic acid or artificial cerebrospinal fluid was infused into the VH of 3- (PD3) or 14- (PD14)-day-old rat pups. Amphetamine-induced (1.5 mg/kg, i.p.) locomotor activity was assessed in the sham and lesioned rats prior to (PD35) and after puberty (PD56 and PD86). Apomorphine-induced (0.75 mg/kg s.c.) stereotypic behaviors were measured on PD56. Similar VH lesions resulted in different profiles of behavioral abnormalities depending upon the age at which they were induced. The PD3 lesioned rats displayed hyperlocomotion to amphetamine only after puberty, while the PD14 lesioned rats manifest hyperlocomotion as early as 3 weeks after surgery (at PD35). Moreover, the PD3 lesioned rats tended to show more stereotypic behaviors in response to apomorphine than the sham-operated controls, while the PD14 rats had a profoundly diminished stereotypic response. The behavioral changes in the PD3 lesioned rats are reminiscent of those previously described in animals lesioned at PD7. In contrast, the deficits in the PD14 lesioned animals resemble those seen before in rats lesioned in adulthood. These results indicate that the pattern of impairments associated with the excitotoxic VH lesion varies with age at lesion, i.e. a similar pattern seems to be associated with lesions up to PD7, but not by PD14. To the extent that the neonatal VH lesion in the rat models certain phenomenological aspects of schizophrenia, including the temporal pattern of symptom onset, these results provide evidence that the model requires an early defect in limbic cortical development. (C) 1997 Elsevier Science B.V. C1 NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,NIH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. RI Lipska, Barbara/E-4569-2017 NR 59 TC 53 Z9 53 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JUL 18 PY 1997 VL 101 IS 1-2 BP 17 EP 25 DI 10.1016/S0165-3806(97)00050-3 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA XP152 UT WOS:A1997XP15200003 ER PT J AU Cloud, JL Marconi, RT Eggers, CH Garon, CF Tilly, K Samuels, DS AF Cloud, JL Marconi, RT Eggers, CH Garon, CF Tilly, K Samuels, DS TI Cloning and expression of the Borrelia burgdorferi lon gene SO GENE LA English DT Article DE Lyme disease; ATP-dependent protease; lpxA; temperature-sensitive mutant ID ATP-DEPENDENT PROTEASE; ESCHERICHIA-COLI; MYXOCOCCUS-XANTHUS; ION GENE; NUCLEOTIDE-SEQUENCE; BACILLUS-SUBTILIS; ENCODES; LA AB The ATP-dependent protease Lon (La) of Escherichia coli degrades abnormal proteins and is involved in the regulation of capsular polysaccharide synthesis. In addition, mutations in the E. coli ion gene suppress temperature-sensitive mutations in other genes. The ion gene of Borrelia burgdorferi, encoding a homolog of the Lon protease, has been cloned and sequenced. The gene encodes a protein of 806 amino acids. The deduced amino acid sequence of the B. burgdorferi Lon protease shares substantial sequence identity with those of other known Lon proteases. The transcription start point of the B. burgdorferi ion gene was identified by primer extension analysis and the potential promoter did not show similarities to the consensus heat-shock promoter in E. coli. The 5'-end of the B. burgdorferi ion gene appears to suppress the temperature-sensitive phenotype of an E. coli lpxA mutant. (C) 1997 Elsevier Science B.V. C1 UNIV MONTANA,DIV BIOL SCI,MISSOULA,MT 59812. MAGIC VALLEY REG MED CTR,TWIN FALLS,ID 83301. NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,HAMILTON,MT 59840. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MICROBIOL & IMMUNOL,RICHMOND,VA 23298. NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 FU NIAID NIH HHS [AI39695, AI37787, R15 AI039695, R15 AI039695-01] NR 20 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 18 PY 1997 VL 194 IS 1 BP 137 EP 141 DI 10.1016/S0378-1119(97)00196-0 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA XN884 UT WOS:A1997XN88400018 PM 9266683 ER PT J AU Bujacz, G Alexandratos, J Wlodawer, A AF Bujacz, G Alexandratos, J Wlodawer, A TI Binding of different divalent cations to the active site of avian sarcoma virus integrase and their effects on enzymatic activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; CATALYTIC DOMAIN; RESOLUTION; PROTEIN; REGION AB Retroviral integrases (INs) contain two known metal binding domains, The N-terminal domain includes a zinc finger motif and has been shown to bind Zn2+, whereas the central catalytic core domain includes a triad of acidic amino acids that bind Mn2+ or Mg2+, the metal cofactors required for enzymatic activity, The integration reaction occurs in two distinct steps; the first is a specific endonucleolytic cleavage step called ''processing,'' and the second is a polynucleotide transfer or ''joining'' step, Our previous results showed that the metal preference for in vitro activity of avian sarcoma virus IN is Mn2+ > Mg2+ and that a single cation of either metal is coordinated by two of the three critical active site residues (Asp-64 and Asp-121) in crystals of the isolated catalytic domain, Here, we report that Ca2+, Zn2+, and Cd2+ can also bind in the active site of the catalytic domain, Furthermore, two zinc and cadmium cations are bound at the active site, with all three residues of the active site triad (Asp-64, Asp-121, and Glu-157) contributing to their coordination, These results are consistent with a two-metal mechanism for catalysis by retroviral integrases, We also show that Zn2+ can serve as a cofactor for the endonucleolytic reactions catalyzed by either the full-length protein, a derivative lacking the N-terminal domain, or the isolated catalytic domain of avian sarcoma virus IN, However, polynucleotidyl transferase activities are severely impaired or undetectable in the presence of Zn2+. Thus, although the processing and joining steps of integrase employ a similar mechanism and the same active site triad, they can be clearly distinguished by their metal preferences. C1 NCI,FREDERICK CANC RES & DEV CTR,MACROMOL STRUCT LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. TECH UNIV LODZ,FAC FOOD CHEM & BIOTECHNOL,PL-90924 LODZ,POLAND. FU NCI NIH HHS [CA-06927, CA-47486] NR 28 TC 116 Z9 122 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 18 PY 1997 VL 272 IS 29 BP 18161 EP 18168 DI 10.1074/jbc.272.29.18161 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL735 UT WOS:A1997XL73500041 PM 9218451 ER PT J AU Pohl, M Silvente-Poirot, S Pisegna, JR Tarasova, NI Wank, SA AF Pohl, M Silvente-Poirot, S Pisegna, JR Tarasova, NI Wank, SA TI Ligand-induced internalization of cholecystokinin receptors - Demonstration of the importance of the carboxyl terminus for ligand-induced internalization of the rat cholecystokinin type B receptor but not the type a receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; AGONIST-INDUCED INTERNALIZATION; SWISS 3T3 CELLS; G-PROTEIN; SIGNAL-TRANSDUCTION; INDUCED DESENSITIZATION; PHEROMONE RECEPTOR; SEQUESTRATION; ENDOCYTOSIS AB Internalization of a variety of different heptahelical G protein-coupled receptors has been shown to be influenced by a number of different structural determinants of the receptors, including the carboxyl terminus. To investigate the role of the carboxyl terminus of cholecystokinin (CCK) receptors in receptor internalization, the rat wild type (WT) CCK-A receptor (WT CCKAR) and the rat WT CCK-B receptor (WT CCKBR) were truncated after amino acid residue 399 (CCKAR Tr399) and 408 (CCKBR Tr408), thereby deleting the carboxyl-terminal 45 and 44 residues, respectively. All WT and mutant CCK receptors were stably expressed in NIH/3T3 cells. Internalization of the CCKAR Tr399 was not significantly different from the WT CCKAR. In contrast, internalization of the CCKBR Tr408 was decreased to 26% compared with the WT CCKBR internalization of 92%. The mutation of all 10 serine and threonine residues (as potential phosphorylation sites) in the carboxyl terminus of the CCKBR to alanines (mutant CCKBR Delta SP/T) could account for the majority of this effect (39% internalization). All mutant receptors displayed similar ligand binding characteristics, G protein coupling, and signal transduction as their respective WT receptors, indicating that the carboxyl termini are not necessary for these processes. Thus, internalization of the CCKBR, unlike that of the CCKAR, depends on the carboxyl terminus of the receptor. These results suggest that, despite the high degree of homology between CCKAR and CCKBR, the structural determinants that mediate the interaction with the endocytic pathway reside in different regions of the receptors. C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOL ASPECTS DRUG DESIGN SECT, FREDERICK, MD 21702 USA. RI Poirot, Sandrine/D-5448-2017 NR 44 TC 34 Z9 34 U1 2 U2 4 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 JUL 18 PY 1997 VL 272 IS 29 BP 18179 EP 18184 DI 10.1074/jbc.272.29.18179 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL735 UT WOS:A1997XL73500043 PM 9218453 ER PT J AU Balla, T Downing, GJ Jaffe, H Kim, S Zolyomi, A Catt, KJ AF Balla, T Downing, GJ Jaffe, H Kim, S Zolyomi, A Catt, KJ TI Isolation and molecular cloning of wortmannin-sensitive bovine type III phosphatidylinositol 4-kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KINASE-ACTIVITY; PROTEIN-KINASE; PHOSPHOINOSITIDE 3-KINASE; SIGNAL TRANSDUCTION; BINDING PROTEIN; PURIFICATION; GENE; CELLS; PHOSPHORYLATION; TRANSFORMATION AB Agonist-sensitive phosphoinositide pools are maintained by recently-identified wortmannin (WT)-sensitive phosphatidylinositol (PI) 4-kinase(s) (Nakanishi, S., Catt, K. J., and Balla, T. (1995) Proc, Natl. Acad. Sci, U.S.A. 92, 5317-5321). Two loosely membrane-associated WT-sensitive type III: PI 4-kinases were isolated from bovine adrenal cortex as [H-3]WT-labeled 110- and 210-kDa proteins, Based on peptide sequences from the smaller enzyme, a 3.9-kilobase pair (kb) cDNA with an open reading frame encoding a 90-kDa protein was isolated from a bovine brain cDNA library, Expression of this cDNA in COS-7 cells yielded a 110-kDa protein with WT-sensitive PI 4-kinase activity. Northern blot analysis of a human mRNA panel showed a single similar to 3.8-kb transcript. Peptide sequences obtained from the 210-kDa enzyme corresponded to those of a recently described rat 230-kDa PI 4-kinase, A 6.5-kb cDNA containing an open reading frame of 6129 nucleotides that encoded a 230-kDa protein, was isolated from brain cDNA, Northern blot analysis of human mRNA revealed a major 7.5-kb transcript, The molecular cloning of these novel WT-sensitive type III PI 4-kinases will allow detailed analysis of their signaling and other regulatory functions in mammalian cells. C1 NINCDS,LNC,PROT PEPTIDE SEQUENCING FACIL,NIH,BETHESDA,MD 20892. RP Balla, T (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BLDG 49,RM 6A36,49 CONVENT DR,BETHESDA,MD 20892, USA. OI Balla, Tamas/0000-0002-9077-3335 NR 52 TC 68 Z9 70 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 JUL 18 PY 1997 VL 272 IS 29 BP 18358 EP 18366 DI 10.1074/jbc.272.29.18358 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL735 UT WOS:A1997XL73500067 PM 9218477 ER PT J AU Kresse, H Liszio, C Schonherr, E Fisher, LW AF Kresse, H Liszio, C Schonherr, E Fisher, LW TI Critical role of glutamate in a central leucine-rich repeat of decorin for interaction with type I collagen SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DERMATAN SULFATE PROTEOGLYCAN; CORE PROTEIN; FIBRILLAR COLLAGEN; TENDON COLLAGEN; BINDING; EXPRESSION; FIBROBLASTS; CDNA; LOCALIZATION; FIBRONECTIN AB The chondroitin/dermatan sulfate proteoglycan decorin is known to interact via its core protein with fibrillar collagens, thereby influencing the kinetics of fibril formation and the final diameter of the fibrils. To define the binding site(s) for type I collagen along the core protein, which is mainly composed of leucine-rich repeat structures, decorin cDNAs were constructed and expressed in human kidney 293 cells. The constructs encoded (i) C-terminally truncated molecules, (ii) core proteins with deletions of selected leucine-rich repeats, or (iii) various point mutations, The deletion of the sixth leucine-rich repeat Met(176)-Lys(201) and the mutation E180K drastically interfered with the binding to reconstituted type I collagen fibrils, In contrast, the deletion of the seventh repeat Leu(202)-Ser(222) led at the most to a marginally impaired binding, although the secretion of this proteoglycan was abnormally low. Decorin with two other point mutations in the sixth leucine-rich repeat, Lys(187) --> Gln and Lys(200) --> Gln, respectively, bound type I collagen either normally or even better than the normal recombinant proteoylycan. These data suggest that a major collagen-binding site of decorin is located within the sixth leucine-rich repeat and that glutamate-180 within this repeat is of special importance for ionic interactions between the two matrix components. C1 NIDR,CRANIOFACIAL & SKELETAL DIS BRANCH,NIH,BETHESDA,MD 20892. RP Kresse, H (reprint author), UNIV MUNSTER,INST PHYSIOL CHEM & PATHOBIOCHEM,WALDEYERSTR 15,D-48149 MUNSTER,GERMANY. NR 50 TC 78 Z9 78 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 JUL 18 PY 1997 VL 272 IS 29 BP 18404 EP 18410 DI 10.1074/jbc.272.29.18404 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XL735 UT WOS:A1997XL73500073 PM 9218483 ER PT J AU Chan, KC Muschik, GM Issaq, HJ AF Chan, KC Muschik, GM Issaq, HJ TI High-speed electrophoretic separation of DNA fragments using a short capillary SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article; Proceedings Paper CT 7th Annual Frederick Conference on Capillary Electrophoresis CY OCT 21-23, 1996 CL HOOD COLL CAMPUS, FREDERICK, MD SP SAIC Frederick, Hood Coll Adm HO HOOD COLL CAMPUS DE DNA ID GEL-ELECTROPHORESIS; PROTEINS; ARRAY AB Capillary electrophoresis using a replaceable gel buffer was applied to the separation of DNA fragments. A short effective length capillary (1-2 cm) at low electric field allowed the separation of a 20-1000 bp ladder in 1 min. Although similar separation speed was achieved with a longer capillary at high held, the resolution of larger fragments was degraded. The short effective length capillaries were able to separate the wildtype and mutant PCR products of the TGF-beta(1) gene in under 45 s. RP Chan, KC (reprint author), NCI,CHEM SYNTH & ANAL LAB,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 11 TC 25 Z9 27 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD JUL 18 PY 1997 VL 695 IS 1 BP 113 EP 115 DI 10.1016/S0378-4347(97)00257-0 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XN723 UT WOS:A1997XN72300013 PM 9271135 ER PT J AU Sanders, JM Burka, LT Shelby, MD Newbold, RR Cunningham, ML AF Sanders, JM Burka, LT Shelby, MD Newbold, RR Cunningham, ML TI Determination of tamoxifen and metabolites in serum by capillary electrophoresis using a nonaqueous buffer system SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article; Proceedings Paper CT 7th Annual Frederick Conference on Capillary Electrophoresis CY OCT 21-23, 1996 CL HOOD COLL CAMPUS, FREDERICK, MD SP SAIC Frederick, Hood Coll Adm HO HOOD COLL CAMPUS DE tamoxifen; N-desmethyltamoxifen; 4-hydroxytamoxifen ID BREAST-CANCER; MOUSE; RAT AB Tamoxifen (TAM), an antiestrogen, is widely used to treat hormone-dependent breast cancer in post-menopausal women. TAM may be used as a chemopreventive agent in women of child-bearing age; however, few data exist describing potential TAM-induced fetal toxicity. In support of the National Toxicology Program's characterization of reproductive and developmental effects of TAM, this work describes an analytical technique utilizing capillary electrophoresis (CE) for the detection of circulating levels of TAM, N-desmethyltamoxifen (DMT), and 4-hydroxytamoxifen (4-HT) in maternal rodent serum. Greater than 90% of H-3-labeled TAM was extractable from serum using 98:2 hexane-isoamyl alcohol. Optimum separation of TAM, DMT, and 4-HT was obtained on a 57 cmX50 mu m capillary using a nonaqueous buffer system of 1:1 methanol-acetonitrile containing 50 mM ammonium acetate and 1% acetic acid. 4-Dimethylaminopyridine was used as internal standard. Temperature and voltage were optimized at 40 degrees C and 15 kV, respectively. The limit of detection of TAM by UV detection at 214 nm was approximately 800 amol. TAM and DMT were confirmed in serum of female rats 4 h following a single oral dose of 120 mg/kg. Transplacental exposure of TAM to fetal tissue will be evaluated using this technique. RP Sanders, JM (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 14 TC 29 Z9 30 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD JUL 18 PY 1997 VL 695 IS 1 BP 181 EP 185 DI 10.1016/S0378-4347(97)00099-6 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA XN723 UT WOS:A1997XN72300021 PM 9271143 ER PT J AU Liang, F Navarro, HA Abraham, P Kotian, P Ding, YS Fowler, J Volkow, N Kuhar, MJ Carroll, FI AF Liang, F Navarro, HA Abraham, P Kotian, P Ding, YS Fowler, J Volkow, N Kuhar, MJ Carroll, FI TI Synthesis and nicotinic acetylcholine receptor binding properties of exo-2-(2'-fluoro-5'-pyridinyl)-7-azabicyclo-[2.2.1]heptane: A new positron emission tomography ligand for nicotinic receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID EPIBATIDINE; (+)-EPIBATIDINE; (-)-EPIBATIDINE; (+/-)-EPIBATIDINE; POISON; BRAIN; FROG C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. BROOKHAVEN NATL LAB,UPTON,NY 11973. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. FU NINDS NIH HHS [NS15380] NR 27 TC 55 Z9 56 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 18 PY 1997 VL 40 IS 15 BP 2293 EP 2295 DI 10.1021/jm970187d PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XL787 UT WOS:A1997XL78700002 PM 9240344 ER PT J AU Cushman, M He, HM Katzenellenbogen, JA Varma, RK Hamel, E Lin, CM Ram, S Sachdeva, YP AF Cushman, M He, HM Katzenellenbogen, JA Varma, RK Hamel, E Lin, CM Ram, S Sachdeva, YP TI Synthesis of analogs of 2-methoxyestradiol with enhanced inhibitory effects on tubulin polymerization and cancer cell growth SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ENDOGENOUS MAMMALIAN METABOLITE; COLCHICINE BINDING-SITE; ANGIOGENESIS; ESTRADIOL; ETHER AB A new series of estradiol analogs was synthesized in an attempt to improve on the anticancer activity of 2-methoxyestradiol, a naturally occurring mammalian tubulin polymerization inhibitor. The compounds were evaluated as inhibitors of tubulin polymerization and the binding of [H-3]colchicine to tubulin, as well as for in vitro cytotoxicity in human cancer cell cultures. Overall, the most potent of the new compounds were 2-(2',2',2'-trifluoroethoxy)-6-oximinoestradiol, 2-ethoxy-6-oximinoestradiol, and 2-ethoxy-6-methoximinoestradiol. These agents lacked significant affinity for the estrogen receptor. The cytotoxicities of the compounds correlated in general with their abilities to inhibit tubulin polymerization, thus supporting inhibition of tubulin polymerization as the primary mechanism causing inhibition of cell growth. C1 UNIV ILLINOIS,DEPT CHEM,URBANA,IL 61801. NCI,DRUG SYNTH & CHEM BRANCH,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,ROCKVILLE,MD 20852. NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. PHARM ECO LABS INC,LEXINGTON,MA 02173. RP Cushman, M (reprint author), PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & MOL PHARMACOL,W LAFAYETTE,IN 47907, USA. FU NCI NIH HHS [N01-CM-17512, N01-CM-27764] NR 46 TC 84 Z9 86 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 18 PY 1997 VL 40 IS 15 BP 2323 EP 2334 DI 10.1021/jm9700833 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA XL787 UT WOS:A1997XL78700006 PM 9240348 ER PT J AU Boullin, JM AF Boullin, JM TI Privatization of a journal SO SCIENCE LA English DT Letter RP Boullin, JM (reprint author), OXFORD UNIV PRESS,JOURNAL NATL CANC INST,9030 OLD GEORGETOWN RD,BETHESDA,MD 20814, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 18 PY 1997 VL 277 IS 5324 BP 297 EP 298 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL358 UT WOS:A1997XL35800003 PM 9518352 ER PT J AU VarghaKhadem, F Gadian, DG Watkins, KE Connelly, A VanPaesschen, W Mishkin, M AF VarghaKhadem, F Gadian, DG Watkins, KE Connelly, A VanPaesschen, W Mishkin, M TI Differential effects of early hippocampal pathology on episodic and semantic memory SO SCIENCE LA English DT Article ID RHESUS-MONKEYS; ASSOCIATION; IMPAIRMENT; EPILEPSY; AMNESIA; CORTEX AB Global anterograde amnesia is described in three patients with brain injuries that occurred in one case at birth, in another by age 4, and in the third at age 9. Magnetic resonance techniques revealed bilateral hippocampal pathology in ail three cases. Remarkably, despite their pronounced amnesia For the episodes of everyday life, all three patients attended mainstream schools and attained levels of speech and language competence, literacy, and factual knowledge that are within the low average to average range. The findings provide support for the view that the episodic and semantic components of cognitive memory are partly dissociable, with only the episodic component being fully dependent an the hippocampus. C1 UCL, SCH MED, INST CHILD HLTH, RADIOL & PHYS UNIT, LONDON WC1N 1EH, ENGLAND. INST NEUROL, LONDON WC1N 3BG, ENGLAND. NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. RP VarghaKhadem, F (reprint author), UCL, SCH MED,WOLFSON CTR,INST CHILD HLTH, COGNIT NEUROSCI UNIT, MECKLENBURGH SQ, LONDON WC1N 2AP, ENGLAND. RI Gadian, David/C-4961-2008; Vargha-Khadem, Faraneh/C-2558-2008; Van Paesschen, Wim/A-4540-2010; Watkins, Kate/A-6559-2012; Connelly, Alan/A-9065-2013; OI Van Paesschen, Wim/0000-0002-8535-1699; Watkins, Kate/0000-0002-2621-482X FU Wellcome Trust NR 36 TC 973 Z9 990 U1 13 U2 93 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 18 PY 1997 VL 277 IS 5324 BP 376 EP 380 DI 10.1126/science.277.5324.376 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL358 UT WOS:A1997XL35800048 PM 9219696 ER PT J AU Polymeropoulos, MH AF Polymeropoulos, MH TI Genetic complexity and Parkinson's disease - Response SO SCIENCE LA English DT Article RP Polymeropoulos, MH (reprint author), NIH,NATL HUMAN GENOME RES INST,LAB GENET DIS RES,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 18 PY 1997 VL 277 IS 5324 BP 389 EP 389 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL358 UT WOS:A1997XL35800053 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI Hitchhiking with peptides SO SCIENCE LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 1 TC 1 Z9 1 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 JUL 18 PY 1997 VL 277 IS 5324 BP 397 EP 398 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL358 UT WOS:A1997XL35800058 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Jurassic mouse SO SCIENCE LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Sikorski, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 18 PY 1997 VL 277 IS 5324 BP 397 EP 397 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL358 UT WOS:A1997XL35800057 ER PT J AU Sikorski, R Peters, R AF Sikorski, R Peters, R TI Robot spotting SO SCIENCE LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Sikorski, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 18 PY 1997 VL 277 IS 5324 BP 398 EP 399 DI 10.1126/science.277.5324.398 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL358 UT WOS:A1997XL35800059 ER PT J AU Schoen, TJ Chandrasekharappa, SC Guru, SC Mazuruk, K Chader, GJ Rodriguez, IR AF Schoen, TJ Chandrasekharappa, SC Guru, SC Mazuruk, K Chader, GJ Rodriguez, IR TI Human gene for the RNA polymerase II seventh subunit (hsRPB7): Structure, expression and chromosomal localization SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE chromosome 11; mapping; GATA repeat ID TRANSCRIPTION; DYSTROPHY; MARKERS; HYBRIDS; REGION; REPAIR; CANCER AB The human gene for the seventh largest subunit of RNA polymerase II complex, hsRPB7 was cloned, sequenced and mapped. This complex is an integral part of the transcription-coupled DNA repair mechanism and has been shown to be involved in several human genetic diseases and implicated in many others. The hsRPB7 gene consists of 8 exons and spans approximately 5.1 kb. Southern blots of genomic and cloned DNA suggest that hsRPB7 is coded for by a single gene. Using human radiation hybrids and YACs, the gene was localized to 11q13.1, within 70 kb of marker D11S1765. The sequence of the 5' flanking region does not contain a TATA element, but does contain several Spl binding sites, an AP-1 site and a novel inverted polymorphic GATA tandem repeat. This novel GATA repeat can be used for linkage analysis. The hsRPB7 gene seems to be highly conserved among eukaryotic species, showing general sequence conservation to yeast and Drosophila. Northern blot analysis reveals a high degree of tissue-specific expression. For example, adult retina, brain and kidney exhibit a relatively high level of expression. A moderate level of expression is observed in heart, lung, testis, cornea, retinal pigmented epithelium/choroid and placenta with a lower level of expression in the uterus, small intestine and skeletal muscle. A very low level of expression was observed in stomach and liver. Comparison between four fetal and adult tissues also demonstrate a surprising level of developmental specificity. Expression in fetal retina is considerably lower than fetal brain but similar to adult retina. (C) 1997 Published by Elsevier Science B.V. C1 NEI,NIH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 23 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD JUL 17 PY 1997 VL 1353 IS 1 BP 39 EP 49 DI 10.1016/S0167-4781(97)00041-9 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XL422 UT WOS:A1997XL42200007 PM 9256063 ER PT J AU Slavc, I Rodriguez, IR Mazuruk, K Chader, GJ Biegel, JA AF Slavc, I Rodriguez, IR Mazuruk, K Chader, GJ Biegel, JA TI Mutation analysis and loss of heterozygosity of PEDF in central nervous system primitive neuroectodermal tumors SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EPITHELIUM-DERIVED FACTOR; P53 GENE-MUTATIONS; RETINOBLASTOMA CELLS; NEURITE OUTGROWTH; 17P DELETIONS; MEDULLOBLASTOMAS; EXPRESSION; CHILDHOOD; 17P13.3; SERPIN AB Deletion of 17p is the most frequent abnormality observed in central nervous system (CNS) primitive neuroectodermal tumors (PNETs), implicating the presence of a tumor suppressor gene which maps to 17p. The gene for pigment epithelium-derived factor (PEDF) has been cloned and mapped to 17p13. PEDF belongs to the serine protease inhibitor (SERPIN) gene family. The PEDF protein has neurotrophic and neuronal-survival activities and is expressed in the CNS. Twenty tumor and matched normal DNA samples from patients with PNETs were screened by single-strand conformation polymorphism (SSCP) analysis to determine loss of heterozygosity (LOH) and to identify potential mutations within the 8 exons of the PEDF gene. Ten of the 20 tumors demonstrated LOH, consistent with the deletion status of 17p determined by cytogenetic or fluorescence in site hybridization studies. SSCP analysis of the genomic DNA from the IO cases with LOH demonstrated several polymorphisms in exons 4 and 7, but no mutations. Our results are consistent with a loss of alleles on 17p in 50% of CNS PNETs, but do not suggest that PEDF is a candidate for the PNET suppressor gene in 17p 13. (C) 1997 Wiley-Liss, Inc. C1 NEI,NIH,BETHESDA,MD 20892. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. RP Slavc, I (reprint author), UNIV VIENNA,KINDERKLIN,DEPT PEDIAT,WAHRINGER GURTEL 18-20,A-1090 VIENNA,AUSTRIA. FU NCI NIH HHS [R01 CA46274] NR 29 TC 7 Z9 8 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 17 PY 1997 VL 72 IS 2 BP 277 EP 282 DI 10.1002/(SICI)1097-0215(19970717)72:2<277::AID-IJC13>3.0.CO;2-D PG 6 WC Oncology SC Oncology GA XH810 UT WOS:A1997XH81000013 PM 9219833 ER PT J AU Haluska, FG Thiele, C Goldstein, A Tsao, H Benoit, EP Housman, D AF Haluska, FG Thiele, C Goldstein, A Tsao, H Benoit, EP Housman, D TI Lack of phospholipase A(2) mutations in neuroblastoma, melanoma and colon-cancer cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN COLORECTAL-CANCER; INTESTINAL NEOPLASIA; DYSPLASTIC NEVUS; MAJOR MODIFIER; MOM1 LOCUS; GENE; DELETIONS; CANDIDATE; MAPS AB A candidate murine tumor-suppressor gene, Mom1, has been identified as the secretory phospholipase A2 (GDB nomenclature: PLA2G2A) gene. Evidence suggests that PLA2G2A functions as a tumor-suppressor because mice lacking PLA2G2A expression demonstrate increased colonic polyposis, The human homologue of PLA2G2A has been mapped to chromosome 1p36, a region frequently implicated in the pathogenesis of neuroblastoma, colon cancer and melanoma. We identified 2 alterations in the PLA2G2A gene in a single neuroblastoma cell line out of 20 examined; however, we found no mutations in 24 melanoma cell lines, 12 lymphoblastoid cell lines from patients having chromosome 1-linked familial melanoma and 10 colon cancer cell lines, Secretory phospholipase A2 is unlikely to play a significant role in the pathogenesis of these tumors. (C) 1997 Wiley-Liss, Inc. C1 MIT,CTR CANC RES,CAMBRIDGE,MA 02139. NCI,CELL & MOL BIOL SECT,PEDIAT BRANCH,NIH,BETHESDA,MD. NIH,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. RP Haluska, FG (reprint author), MASSACHUSETTS GEN HOSP,DEPT HEMATOL ONCOL,COX BLDG,ROOM 640,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 20 TC 18 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 17 PY 1997 VL 72 IS 2 BP 337 EP 339 DI 10.1002/(SICI)1097-0215(19970717)72:2<337::AID-IJC22>3.0.CO;2-B PG 3 WC Oncology SC Oncology GA XH810 UT WOS:A1997XH81000022 PM 9219842 ER PT J AU Spoonster, JR Masiero, L Savage, SA Probst, J Kohn, EC AF Spoonster, JR Masiero, L Savage, SA Probst, J Kohn, EC TI Regulation of cell spreading during differentiation in the muscarinic M5 receptor tumor-suppressor model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID FOCAL ADHESION KINASE; PROTEIN-TYROSINE KINASE; ARACHIDONIC-ACID RELEASE; SIGNAL-TRANSDUCTION; CALCIUM INFLUX; GROWTH-FACTOR; ACETYLCHOLINE-RECEPTORS; PHOSPHORYLATION; PP125(FAK); ASSOCIATION AB Activation of the muscarinic receptor in Chinese hamster ovary (CHO) cells results in a reversal of the malignant phenotype for which spreading into a bipolar, fibroblastic morphology is a marker. The process of morphologic change requires multiple events, including alterations in adhesions to substrates and cytoskeletal re-arrangement, In this report, we demonstrate the calcium-dependent involvement of p125(FAK) in this cellular shape change using an inhibitor of ligand-induced calcium influx, carboxyamido-triazole (CAI), p125(FAK) becomes tyrosine-phosphorylated after exposure to the agonist carbachol (CC), reaching maximal phosphorylation prior to initiation of cellular shape change at 1 hr into CC exposure (386 +/- 103%), Phosphorylation remained elevated through the shape change (4-12 hr). CHOm5 cell exposure to the Ca2+-mobilizing agents maitotoxin and ionomycin also resulted in p125(FAK) phosphorylation. Inhibition of Ca2+ influx with CAI, an inhibitor of ligand-induced Ca2+ influx, had little effect on CC-induced phosphorylation but partially inhibited ionomycin-mediated p125(FAK) phosphorylation. While the intracellular Ca2+ chelator BAPTA failed to prevent CC-induced p125(FAK) tyrosine phosphorylation, it inhibited phosphorylation due to ionomycin, CC induced Ca2+-independent binding of phosphorylated p125(FAK) selectively to the C-terminal SH2 domain of phosphatidylinositol-3'-kinase (PI3K). Further, CC, maitotoxin and ionomycin induced in vitro kinase activity of p125(FAK) for the exogenous substrate poly(Glu(4)Tyr(1),), Kinase activity stimulated by all 3 agonists was inhibited by preincubation with either CAI or BAPTA. Our results indicate that increasing intracellular Ca2+ can stimulate both p125(FAK) autophosphorylation and kinase activity; however, p125(FAK) phosphorylation in response to CC also may be induced through a Ca2+-independent pathway. (C) 1997 Wiley-Liss, Inc. C1 NCI, PATHOL LAB, MOL SIGNALING SECT, BETHESDA, MD 20892 USA. RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 40 TC 6 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 17 PY 1997 VL 72 IS 2 BP 362 EP 368 DI 10.1002/(SICI)1097-0215(19970717)72:2<362::AID-IJC27>3.0.CO;2-G PG 7 WC Oncology SC Oncology GA XH810 UT WOS:A1997XH81000027 PM 9219847 ER PT J AU Alkhatib, G Liao, F Berger, EA Farber, JM Peden, KWC AF Alkhatib, G Liao, F Berger, EA Farber, JM Peden, KWC TI A new SIV co-receptor, STRL33 SO NATURE LA English DT Letter C1 NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,RETROVIRUS RES LAB,BETHESDA,MD 20892. RP Alkhatib, G (reprint author), NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892, USA. NR 18 TC 105 Z9 109 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 JUL 17 PY 1997 VL 388 IS 6639 BP 238 EP 238 DI 10.1038/40789 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL121 UT WOS:A1997XL12100035 PM 9230431 ER PT J AU Raymond, GJ Hope, J Kocisko, DA Priola, SA Raymond, LD Bossers, A Ironside, J Will, RG Chen, SG Petersen, RB Gambetti, P Rubenstein, R Smits, MA Lansbury, PT Caughey, B AF Raymond, GJ Hope, J Kocisko, DA Priola, SA Raymond, LD Bossers, A Ironside, J Will, RG Chen, SG Petersen, RB Gambetti, P Rubenstein, R Smits, MA Lansbury, PT Caughey, B TI Molecular assessment of the potential transmissibilities of BSE and scrapie to humans SO NATURE LA English DT Article ID BOVINE SPONGIFORM ENCEPHALOPATHY; PRION PROTEIN; SHEEP; GENOTYPE; FIBRILS; DISEASE; CATTLE; MICE; PRP AB More than a million cattle infected with bovine spongiform encephalopathy (BSE) may have entered the human food chain(1). Fears that BSE might transmit to man were raised when atypical cases of Creutzfeldt-Jakob disease (CJD), a human transmissible spongiform encephalopathy (TSE), emerged in the UK2,3. I, BSE and other TSE diseases, the conversion of the protease-sensitive host prion protein (PrP-sen) to a protease-resistant isoform (PrP-res) is an important event in pathogenesis(4-7). Biological aspects of TSE diseases are reflected in the specificities of in vitro PrP conversion reactions(8-12). Here we show that there is a correlation between in vitro conversion efficiencies and known transmissibilities of BSE, sheep scrapie and CJD. On this basis, we used an in vitro system to gauge the potential transmissibility of scrapie and BSE to humans. We found Limited conversion of human PrP-sen to PrP-res driven by PrP-res associated with both scrapie (PrPSc) and BSE (prp(BSE)). The efficiencies of these heterologous conversion reactions were similar but much lower than those of relevant homologous conversions. Thus the inherent ability of these infectious agents of BSE and scrapie to affect humans following equivalent exposure may be finite but similarly low. C1 BBSRC,INST ANIM HLTH,COMPTON LAB,NEWBURY RG20 7NN,BERKS,ENGLAND. NIAID,ROCKY MT LABS,NIH,HAMILTON,MT 59840. MIT,DEPT CHEM,CAMBRIDGE,MA 02139. DLO,INST ANIM SCI & HLTH,DEPT BACTERIOL,NL-8200 AB LELYSTAD,NETHERLANDS. WESTERN GEN HOSP,CJD SURVEILLANCE UNIT,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NEW YORK STATE INST BASIC RES DEV DISABIL,NEW YORK,NY 10314. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,BOSTON,MA 02115. RI Petersen, Robert/B-5075-2011; Hope, James/C-4966-2011; smits, mari/J-4892-2013; Chen, Shu/O-4750-2014; OI Petersen, Robert/0000-0002-3154-0072; smits, mari/0000-0002-3493-291X; Chen, Shu/0000-0001-7180-3001; Bossers, Alex/0000-0002-6586-717X NR 26 TC 201 Z9 207 U1 1 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 17 PY 1997 VL 388 IS 6639 BP 285 EP 288 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL121 UT WOS:A1997XL12100053 PM 9230438 ER PT J AU Rowe, JA Moulds, JM Newbold, CI Miller, LH AF Rowe, JA Moulds, JM Newbold, CI Miller, LH TI P-falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1 SO NATURE LA English DT Article ID PLASMODIUM-FALCIPARUM; INFECTED ERYTHROCYTES; SWAIN-LANGLEY; MALARIA; EXPRESSION; PHENOTYPES; CYTOADHERENCE; ANTIGENS; SURFACE; DOMAINS AB The factors determining disease severity in malaria are complex and include host polymorphisms, acquired immunity and parasite virulence(1). Studies in Africa have shown that severe malaria is associated with the ability of erythrocytes infected with the parasite Plasmodium falciparum to bind uninfected erythrocytes and form rosettes(2-5). The molecular basis of resetting is not well understood, although a group of low-molecular-mass proteins called rosettins have been described as potential parasite ligands(6). Infected erythrocytes also bind to endothelial cells, and this interaction is mediated by the parasite-derived variant erythrocyte membrane protein PfEMP1 (refs 7, 8), which is encoded by the var gene family(9-11). Here we report that the parasite ligand for resetting in a P. falciparum done is PfEMP1, encoded by a specific var gene, We also report that Complement-receptor 1 (CR1) on erythrocytes plays a role in the formation of rosettes and that erythrocytes with a common African CR1 polymorphism (Sl(a(-)))(12) have reduced adhesion to the domain of PfEMP1 that binds normal erythrocytes. Thus we describe a new adhesive function for PfEMP1 and raise the possibility that CR1 polymorphisms in Africans that influence the interaction between erythrocytes and PfEMP1 may protect against severe malaria. C1 JOHN RADCLIFFE HOSP,INST MOL MED,MOL PARASITOL GRP,OXFORD OX3 9DU,ENGLAND. UNIV TEXAS,HOUSTON MED SCH,DIV RHEUMATOL & CLIN IMMUNOGENET,HOUSTON,TX 77030. RP Rowe, JA (reprint author), NIAID,PARASIT DIS LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Newbold, Chris/0000-0002-9274-3789 FU Wellcome Trust NR 29 TC 387 Z9 393 U1 2 U2 15 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 17 PY 1997 VL 388 IS 6639 BP 292 EP 295 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA XL121 UT WOS:A1997XL12100055 PM 9230440 ER PT J AU Koh, KK Cannon, RO AF Koh, KK Cannon, RO TI Hormone-replacement therapy and coagulation - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Koh, KK (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. RI Davis, Susan/A-3111-2009 NR 4 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 JUL 17 PY 1997 VL 337 IS 3 BP 201 EP 202 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA XK818 UT WOS:A1997XK81800019 ER PT J AU Landsberger, N Wolffe, AP AF Landsberger, N Wolffe, AP TI Remodeling of regulatory nucleoprotein complexes on the Xenopus hsp70 promoter during meiotic maturation of the Xenopus oocyte SO EMBO JOURNAL LA English DT Article DE heat shock; meiosis; nucleoprotein; transcription repression; Xenopus ID RNA-POLYMERASE-II; NUCLEOSOME ASSEMBLY INVITRO; TRANSCRIPTION IN-VIVO; HEAT-SHOCK PROMOTER; GENE-TRANSCRIPTION; SOMATIC-CELLS; CHROMATIN TEMPLATES; DNA-REPLICATION; LAEVIS OOCYTES; TBP BINDING AB Transcriptional repression occurs during meiotic maturation of Xenopus oocytes. Injection of a DNA template containing an hsp70 promoter into Xenopus oocytes, followed by progesterone-induced maturation has been used to demonstrate a dynamic competition between the assembly of transcription factor-containing nucleoprotein complexes and repressive nucleosomal arrays during the maturation process. In particular, it is shown that increased levels of injected heat shock protein, the transcriptional activator Gal4-VP16 or the DNA template itself all lead to reduced repression of transcription on maturation. Conversely, injection of additional histone increases repression, Repression of transcription is shown to be accompanied by the formation of a more regular array of nucleosomes and by an increase in the efficiency of nucleosome assembly on the injected plasmid. Meiotic maturation is therefore accompanied by replacement of transcription factor complexes by a repressive chromatin environment. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. OI Landsberger, Nicoletta/0000-0003-0820-3155 NR 79 TC 20 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 16 PY 1997 VL 16 IS 14 BP 4361 EP 4373 DI 10.1093/emboj/16.14.4361 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XM406 UT WOS:A1997XM40600022 PM 9250680 ER PT J AU Kostis, JB Davis, BR Cutler, J Grimm, RH Berge, KG Cohen, JD Lacy, CR Perry, HM Blaufox, MD WassertheilSmoller, S Black, HR Schron, E Berkson, DM Curb, JD Smith, WM McDonald, R Applegate, WB AF Kostis, JB Davis, BR Cutler, J Grimm, RH Berge, KG Cohen, JD Lacy, CR Perry, HM Blaufox, MD WassertheilSmoller, S Black, HR Schron, E Berkson, DM Curb, JD Smith, WM McDonald, R Applegate, WB TI Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; UNITED-STATES; MORTALITY; MORBIDITY; TRIAL; PREVALENCE AB Context.-Heart failure is often preceded by isolated systolic hypertension, but the effectiveness of antihypertensive treatment in preventing heart failure is not known. Objective.-To assess the effect of diuretic-based antihypertensive stepped-care treatment on the occurrence of heart failure in older persons with isolated systolic hypertension. Design.-Analysis of data from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Participants.-A total of 4736 persons aged 60 years and older with systolic blood pressure between 160 and 219 mm Hg and diastolic blood pressure below 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP). Intervention.-Stepped-care antihypertensive drug therapy, in which the step 1 drug is chlorthalidone (12.5-25 mg) or matching placebo, and the step 2 drug is atenolol (25-50 mg) or matching placebo. Main Outcome Measures.-Fatal and nonfatal heart failure. Results.-During an average of 4.5 years of follow-up, fatal or nonfatal heart failure occurred in 55 of 2365 patients randomized to active therapy and 105 of the 2371 patients randomized to placebo (relative risk [RR], 0.51; 95% confidence interval [CI], 0.37-0.71; P<.001; number needed to treat to prevent 1 event [NNT], 48). Among patients with a history of or electrocardiographic evidence of prior myocardial infarction (MI), the RR was 0.19 (95% CI, 0.06-0.53; P=.002; NNT, 15). Older patients, men, and those with higher systolic blood pressure or a history of or electrocardiographic evidence of MI at baseline had higher risk of developing heart failure. Conclusion.-In older persons with isolated systolic hypertension, stepped-care treatment based on low-dose chlorthalidone exerted a strong protective effect in preventing heart failure. Among patients with prior MI, an 80% risk reduction was observed. C1 UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX. NHLBI,BETHESDA,MD 20892. MINNEAPOLIS MED RES FDN INC,SHAPIRO CTR EVIDENCE BASED MED,MINNEAPOLIS,MN. UNIV MINNESOTA,MINNEAPOLIS,MN. MAYO CLIN & MAYO FDN,MAYO MED SCH,DEPT INTERNAL MED,ROCHESTER,MN 55905. ALBERT EINSTEIN COLL MED,DEPT NUCL MED,BRON,FRANCE. ALBERT EINSTEIN COLL MED,DEPT SOCIAL MED,BRON,FRANCE. ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL,BRON,FRANCE. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PREVENT MED,CHICAGO,IL 60612. NORTHWESTERN UNIV,SCH MED,DEPT MED,CHICAGO,IL 60611. IDA & NORMAN STONE MED CTR,CHICAGO,IL. UNIV HAWAII,JOHN A BURNS SCH MED,DEPT MED,HONOLULU,HI 96822. PACIFIC HLTH RES INST,HONOLULU,HI. SRI INT,DIV HLTH SCI,MENLO PK,CA 94025. UNIV PITTSBURGH,SCH MED,DEPT MED,PITTSBURGH,PA. UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN. RP Kostis, JB (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MED,NEW BRUNSWICK,NJ 08903, USA. NR 25 TC 238 Z9 244 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 16 PY 1997 VL 278 IS 3 BP 212 EP 216 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XK108 UT WOS:A1997XK10800026 PM 9218667 ER PT J AU Mullins, LS Hong, SB Gibson, GE Walker, H Stadtman, TC Raushel, FM AF Mullins, LS Hong, SB Gibson, GE Walker, H Stadtman, TC Raushel, FM TI Identification of a phosphorylated enzyme intermediate in the catalytic mechanism for selenophosphate synthetase SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ESCHERICHIA-COLI; SELENOCYSTEINE SYNTHASE; SELENIUM DONOR; TRANSFER-RNAS; PURIFICATION; SEQUENCE; ATP C1 TEXAS A&M UNIV,DEPT CHEM,COLLEGE STN,TX 77843. NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. RI Raushel, Frank/B-7125-2015 OI Raushel, Frank/0000-0002-5918-3089 NR 20 TC 19 Z9 21 U1 0 U2 1 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 JUL 16 PY 1997 VL 119 IS 28 BP 6684 EP 6685 DI 10.1021/ja971074m PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA XL343 UT WOS:A1997XL34300034 ER PT J AU Gordis, L Berry, DA Chu, SY Fajardo, LL Hoel, DG Laufman, LR Rufenbarger, CA Scott, JR Sullivan, DC Wasson, JH Westhoff, CL Zern, RT AF Gordis, L Berry, DA Chu, SY Fajardo, LL Hoel, DG Laufman, LR Rufenbarger, CA Scott, JR Sullivan, DC Wasson, JH Westhoff, CL Zern, RT TI National Institutes of Health Consensus Development Conference Statement: Breast cancer screening for women ages 40-49, January 21-23, 1997 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; POSITIVE PREDICTIVE VALUE; FOLLOW-UP; ABNORMAL MAMMOGRAMS; STATISTICAL POWER; SAMPLE-SIZE; MORTALITY; STOCKHOLM; METAANALYSIS; PREVALENCE AB Objective. To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the effectiveness of mammography screening for women ages 40-49. Participants. A non-Federal, nonadvocate, 12-member panel representing the fields of oncology, radiology, obstetrics and gynecology, geriatrics, public health, and epidemiology and including patient representatives. In addition, 32 experts in oncology, surgical oncology, radiology, public health, and epidemiology, presented data to the panel and to a conference audience of 1,100. Evidence. The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. Consensus Process. The panel, answering predefined questions, developed its conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised draft statement at the end of the conference. The final statement with a minority report was completed within several weeks after the conference. Conclusions. The Panel concludes that the data currently available do not warrant a universal recommendation for mammography for all women in their forties. Each woman should decide for herself whether to undergo mammography. Her decision may be based not only on an objective analysis of the scientific evidence and consideration of her individual medical history, but also on how she perceives and weighs each potential risk and benefit, the values she places on each, and how she deals with uncertainty. However, it is not sufficient just to advise a woman to make her own decision about mammograms. Given both the importance and the complexity of the issues involved in assessing the evidence, a woman should have access to the best possible relevant information regarding both benefits and risks, presented in an understandable and usable form. Information should be developed for women in their forties regarding potential benefits and risks to be provided to enable each woman to make the most appropriate decision, In addition, educational material to accompany this information should be prepared that will lead women step by step through the process of using such information in the best possible way for reaching a decision. For women in their forties who choose to have mammography performed, the costs of the mammograms should be reimbursed by third-party payers or covered by health maintenance organizations so that financial impediments will not influence a woman's decision, Additionally, a woman's health care provider must be equipped with sufficient information to facilitate her decisionmaking process. Therefore, educational material for physicians should be developed to assist them in providing the guidance and support needed by the women in their care who are making difficult decisions regarding mammography, The two panel members writing a minority report believed the risks of mammography to be overemphasized by the majority and concluded that the data did support a recommendation for mammography screening for all women in this age group and that the survival benefit and diagnosis at an earlier stage outweigh the potential risks. RP Gordis, L (reprint author), NIH,OFF MED APPLICAT RES,FED BLDG,RM 618,BETHESDA,MD 20892, USA. NR 94 TC 105 Z9 105 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 JUL 16 PY 1997 VL 89 IS 14 BP 1015 EP 1026 PG 12 WC Oncology SC Oncology GA XL163 UT WOS:A1997XL16300011 ER PT J AU Hayes, RB Yin, SN Dosemeci, M Li, GL Wacholder, S Travis, LB Li, CY Rothman, N Hoover, RN Linet, MS AF Hayes, RB Yin, SN Dosemeci, M Li, GL Wacholder, S Travis, LB Li, CY Rothman, N Hoover, RN Linet, MS TI Benzene and the dose-related incidence of hematologic neoplasms in China SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INDUSTRY WIDE MORTALITY; PLIOFILM COHORT; EXPOSURE ASSESSMENT; WORKERS; LEUKEMIA; RISK; CARCINOGENICITY; UPDATE; MICE AB Background: Benzene is a widely distributed environmental contaminant known to cause leukemia, particularly acute nonlymphocytic leukemia, and perhaps other hematologic neoplasms and disorders, Few epidemiologic studies, however, have been able to address relationships between the extent of benzene exposure and the level of risk. Purpose: A large cohort study was carried out in China to evaluate the risks of developing specific hematologic neoplasms and selected related disorders in relationship to quantitative estimates of occupational benzene exposure, Methods: A cohort of 74828 benzene exposed and 35805 unexposed workers employed from 1972 through 1987 in 12 cities in China was identified and followed to determine the incidence of hematologic neoplasms and related disorders, Estimates of benzene exposure were derived from work histories and available historic benzene measurements, Existing pathologic material and supporting medical records were reviewed to establish diagnoses of disease, Relative risks (RRs) (i.e., ratios of incidence rates for specific hematologic neoplasms and related disorders in the benzene-exposed group to incidence rates in the unexposed group) were determined by use of Poisson regression analysis, with stratification by age and sex, Results: For workers historically exposed to benzene at average levels of less than 10 parts per million (ppm), the RR for all hematologic neoplasms combined was 2.2 (95% confidence interval [CI] = 1.1-4.2), and, for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes, the RR was 3.2 (95% CI = 1.0-10.1), For individuals who were occupationally exposed to benzene at constant levels of 25 ppm or more, the RR for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was 7.1 (95% CI = 2.1-23.7), Workers with 10 or more years of benzene exposure had an RR of developing non-Hodgkin's lymphoma of 4.2 (95% CI = 1.1-15.9), and the development of this neoplasm was linked most strongly to exposure that had occurred at least 10 years before diagnosis (i.e., distant exposure) (P for trend = .005, two-sided), In contrast, the risk for the combination of acute nonlymphocytic leukemia and related myelodysplastic syndromes was significantly increased among those with more recent benzene exposure (P for trend = .003, two-sided), but it was not linked to distant exposure (P for trend = .51, two-sided), Conclusions: The results of this study suggest that benzene exposure is associated with a spectrum of hematologic neoplasms and related disorders in humans, Risks for these conditions are elevated at average benzene-exposure levels of less than 10 ppm and show a tendency, although not a strong one, to rise with increasing levels of exposure, The temporal pattern of benzene exposure appears to be important in determining the risk of developing specific diseases. C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. CHINESE ACAD PREVENT MED,INST OCCUPAT MED,BEIJING 100050,PEOPLES R CHINA. MAYO CLIN,HEMATOPATHOL SECT,ROCHESTER,MN. RI Alejandro Martin, Serguei/A-6593-2012 NR 37 TC 215 Z9 219 U1 0 U2 8 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 16 PY 1997 VL 89 IS 14 BP 1065 EP 1071 DI 10.1093/jnci/89.14.1065 PG 7 WC Oncology SC Oncology GA XL163 UT WOS:A1997XL16300017 PM 9230889 ER PT J AU Wolters, PL Brouwers, P Civitello, L Moss, HA AF Wolters, PL Brouwers, P Civitello, L Moss, HA TI Receptive and expressive language function of children with symptomatic HIV infection and relationship with disease parameters: A longitudinal 24-month follow-up study SO AIDS LA English DT Article DE pediatric HIV infection; language; cognitive; neurodevelopment; encephalopathy; long-term effects ID IMMUNODEFICIENCY-VIRUS-INFECTION; ZIDOVUDINE; THERAPY; ABNORMALITIES; INFUSION; BRAIN; AIDS; BORN AB Objectives: To longitudinally assess the receptive and expressive language functioning of children with symptomatic HIV disease and to explore the relationship between immune status, computed tomography (CT) brain scan abnormalities, and language dysfunction over lime. Methods: Children with symptomatic HIV infection were administered an age-appropriate standardized comprehensive language test and general cognitive measure prior to starting antiretroviral therapy (n = 44) and again after 6 months (n = 29) and 24 months (n = 17). CD4 percentage and CT brain scans were also obtained at each evaluation. Results: Expressive language was significantly more impaired than receptive language at the baseline, 6- and 24-month evaluations. No significant changes over time were found in receptive or expressive language from baseline to after 6 months of antiretroviral therapy, but despite treatment, language scores declined significantly between 6 and 24 months. Overall cognitive function, however, remained stable from baseline to 24 months. Age-adjusted CD4 percentage increased significantly over the initial 6 months, then remained stable. Overall CT brain scan severity ratings did not change significantly over 24 months. Conclusion: Expressive language was consistently more impaired than receptive language over 24 months, further supporting an earlier finding that expressive language was differentially affected by HIV in children with symptomatic disease. Both receptive and expressive language declined significantly after 24 months despite antiretroviral therapy, although overall cognitive function remained stable. Thus, functioning in some domains may be more vulnerable to the effects of HIV and global measures of cognitive ability may mask such differential changes in specific brain functions. C1 MED ILLNESS COUNSELING CTR, CHEVY CHASE, MD USA. CHILDRENS NATL MED CTR, WASHINGTON, DC 20010 USA. RP Wolters, PL (reprint author), NCI, HIV AIDS MALIGNANCY BRANCH,NIH,10 CTR DR,BLDG 10, 13N240, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CM-47002-09, CM-17529-41] NR 33 TC 43 Z9 46 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 15 PY 1997 VL 11 IS 9 BP 1135 EP 1144 DI 10.1097/00002030-199709000-00009 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA XJ644 UT WOS:A1997XJ64400009 PM 9233461 ER PT J AU Kulldorff, M Feuer, EJ Miller, BA Freedman, LS AF Kulldorff, M Feuer, EJ Miller, BA Freedman, LS TI Breast cancer clusters in the northeast United States: A geographic analysis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; cluster analysis; confounding; epidemiologic methods; geography; parity; statistics ID FEMALE ELECTRICAL WORKERS; LONG-ISLAND; MORTALITY; RISK; HYPOTHESIS; ALCOHOL; CONSUMPTION; RADIATION; PATTERNS; 1ST AB High breast cancer mortality rates have been reported in the northeastern part of the United States, with recent attention focused on Long Island, New York. In this study, the authors investigate whether the high breast cancer mortality is evenly spread over the Northeast, in the sense that any observed clusters of deaths can be explained by chance alone, or whether there are clusters of statistical significance. Demographic data and age-specific breast cancer mortality rates for women were obtained for all 244 counties in 11 northeastern states and for the District of Columbia for 1988-1992. A recently developed spatial scan statistic is used, which searches for clusters of cases without specifying their size or location ahead of time, and which tests for their statistical significance while adjusting for the multiple testing inherent in such a procedure. The basic analysis is adjusted for age, with further analyses examining how the results are affected by incorporating race, urbanicity, and parity as confounding variables. There is a statistically significant and geographically broad cluster of breast cancer deaths in the New York City-Philadelphia Pennsylvania, metropolitan area (p = 0.0001), which has a 7.4% higher mortality rate than the rest of the Northeast. The cluster remains significant when race, urbanicity, and/or parity are included as confounding variables. Four smaller subclusters within this area are also significant on their own strength: Philadelphia with suburbs (p = 0.0001), Long Island (p = 0.0001), central New Jersey (p = 0.0001), and northeastern New Jersey (p = 0.0001). The elevated breast cancer mortality on Long Island might be viewed less as a unique local phenomenon and more as part of a more general situation involving large parts of the New York City-Philadelphia metropolitan area. The several known and hypothesized risk factors for which we could not adjust and that may explain the detected cluster are most notably age at first birth, age at menarche, age at menopause, breastfeeding, genetic mutations, and environmental factors. C1 UPPSALA UNIV,DEPT STAT,UPPSALA,SWEDEN. RP Kulldorff, M (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EPN 344,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Kulldorff, Martin/H-4282-2011; OI Kulldorff, Martin/0000-0002-5284-2993 NR 50 TC 200 Z9 206 U1 1 U2 11 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 15 PY 1997 VL 146 IS 2 BP 161 EP 170 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XL764 UT WOS:A1997XL76400007 PM 9230778 ER PT J AU DeCederfelt, HJ Grimes, GJ Green, L DeCederfelt, RO Daniels, CE AF DeCederfelt, HJ Grimes, GJ Green, L DeCederfelt, RO Daniels, CE TI Handling of gene-transfer products by the National Institutes of Health Clinical Center pharmacy department SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE administration; aseptic areas; dispensing; drug distribution systems; drugs, investigational; Food and Drug Administration (US); gene therapy; guidelines; National Institutes of Health; personnel, pharmacy; pharmacy, institutional, hospital; safety AB Policies and procedures for handling gene-transfer products at the National Institutes of Health (NIH) Clinical Center pharmacy department are described. The pharmacy at the Clinical Center is responsible for handling in vivo gene-transfer delivery systems, which are gene-transfer products that are prepared for direct administration to patients. The gene-transfer products currently handled by the pharmacy are investigational and are composed of viruses containing the gene encoding either of the melanoma antigens MART-1 and gp100. The pharmacy has prepared guidelines, based on the principles of aseptic technique and FDA guidelines for manufacturing facilities, intended to help pharmacy personnel safely dilute a concentrated gene-transfer product into a dose suitable for administration. Before a product is handled, the biological safety level is determined and a biohazard sign is posted. Worksheets detailing all supplies, calculations for dilutions, and procedures that will be required are prepared in advance; the worksheets are part of a drug fact sheet prepared for all investigational drugs dispensed. Personnel must be properly trained and dressed in protective clothing. Aseptic technique and decontamination procedures are used as specified in the guidelines, and all materials used are disposed of as biohazardous waste. All work is documented. If a worker is accidentally exposed, standard procedures are followed. The handling of gene-transfer products at the NIH Clinical Center pharmacy is based on the principles of aseptic technique, FDA guide lines, and experience. C1 AMGEN INC,PROFESS SERV,THOUSAND OAKS,CA 91320. RP DeCederfelt, HJ (reprint author), NIH,CC,PHAR,PDS,PHARMACEUT DEV SERV SECT,DEPT PHARM,WARREN GRANT MAGNUSON CLIN CTR,WGMCC,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUL 15 PY 1997 VL 54 IS 14 BP 1604 EP 1610 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XM182 UT WOS:A1997XM18200008 PM 9248603 ER PT J AU Kopp, JB Miller, KD Mican, JAM Feuerstein, IM Vaughan, E Baker, C Pannell, LK Falloon, J AF Kopp, JB Miller, KD Mican, JAM Feuerstein, IM Vaughan, E Baker, C Pannell, LK Falloon, J TI Crystalluria and urinary tract abnormalities associated with indinavir SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE crystalluria; urinary tract; indinavir; human immunodeficiency virus infections; kidney calculi ID PROTEASE INHIBITOR; PATHOGENESIS; L-735,524 AB Background: Indinavir, a protease inhibitor widely used to treat patients with HIV infection, has been associated with nephrolithiasis. Distinctive urinary crystals and a spectrum of urologic disorders were noted in patients receiving indinavir. Objective: To determine the composition of urinary crystals and the frequency of asymptomatic crystalluria and urinary tract symptoms in patients receiving indinavir. Patients: Patients with HIV infection who were enrolled in studies conducted at the National Institutes of Health. Measurements: Microscopic urinalysis, high-performance liquid chromatography (HPLC) and mass spectrometry of urinary crystals and stones, and clinical evaluation of patients with urologic symptoms. Results: Of 240 patients receiving indinavir, 142 provided urine specimens for analysis. Twenty-nine (20%) had crystals consisting of plate-like rectangles and fan-shaped or starburst forms. Mass spectrometry and HPLC confirmed that these crystals were composed of indinavir. OF 40 patients who were not receiving indinavir, none had similar crystals (P < 0.001). Nineteen of the 240 patients receiving indinavir (8%) developed urologic symptoms. Of these, 7 (3%) had nephrolithiasis and the other 12 (5%) had previously undescribed syndromes: crystalluria associated with dysuria and crystalluria associated with back or flank pain. Four of the patients with the latter syndrome had radiographic evidence of intrarenal sludging. Conclusions: Indinavir forms characteristic crystals in the urine. This crystalluria may be associated with dysuria and urinary frequency, with flank or back pain associated with intrarenal sludging, and with the classic syndrome of renal colic. C1 NIAID,NIH,BETHESDA,MD. RP Kopp, JB (reprint author), NIDDK,WARREN GRANT MAGNUSON CLIN CTR,NIH,BLDG 10,ROOM 3N116,BETHESDA,MD 20892, USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 22 TC 213 Z9 217 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 JUL 15 PY 1997 VL 127 IS 2 BP 119 EP & PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA XK158 UT WOS:A1997XK15800006 PM 9230000 ER PT J AU Karp, BI Laureno, R AF Karp, BI Laureno, R TI Hyponatremia and myelinolysis - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID RAPID CORRECTION; SEQUELAE; PONTINE C1 WASHINGTON HOSP CTR,WASHINGTON,DC 20010. RP Karp, BI (reprint author), NIH,BETHESDA,MD 20892, USA. NR 5 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 JUL 15 PY 1997 VL 127 IS 2 BP 163 EP 163 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA XK158 UT WOS:A1997XK15800017 ER PT J AU Washburn, BS Rein, KS Baden, DG Walsh, PJ Hinton, DE Tullis, K Denison, MS AF Washburn, BS Rein, KS Baden, DG Walsh, PJ Hinton, DE Tullis, K Denison, MS TI Brevetoxin-6 (PbTx-6), a nonaromatic marine neurotoxin, is a ligand of the aryl hydrocarbon receptor SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE brevetoxin; marine toxins; natural toxins; Ah receptor; EROD; cytochrome P4501A1 ID AH-RECEPTOR; BINDING; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; QUANTITATION; HYDROXYLASE; INDUCTION; BIPHENYLS; TOXICITY; AGONISTS; PROTEIN AB Brevetoxins (PbTx) are a family of marine polyether toxins that exert their toxic action by activating voltage-sensitive sodium channels. Two forms of brevetoxin, PbTx-2 and -3, induce hepatic cytochrome P4501A1, measured as ethoxyresorufin O-deethylase (EROD) activity, in redfish and striped bass. P4501A1 induction is transcriptionally regulated through the binding of a ligand, typically a planar aromatic compound, to the aryl hydrocarbon receptor (AhR) and subsequent complex formation with the dioxin response element (DRE), an upstream regulatory region of the CYP1A1 gene. To determine if PbTx, a nonaromatic compound, induced EROD by this mechanism, two sets of experiments were performed. Initially, saturation binding assays with PbTx-2, -3, and -6 were carried out to determine if PbTx-2, -3, or -6 was an AhR ligand. Results showed that PbTx-6 inhibited specific binding of dioxin to the AhR, whereas PbTx-2 and -3 had no effect. Subsequently, gel retardation assays showed that PbTx-6 caused a concentration-dependent increase in AhR-DRE complex formation. The most abundant and neurotoxic forms of brevetoxin, PbTx-2 and -3, did not appear to be involved in this process. However, PbTx-6, the epoxide which is a likely biotransformation product, is at least one of the forms of PbTx involved in EROD induction. (C) 1997 Academic Press. C1 UNIV CALIF DAVIS,SCH VET MED,DEPT ANAT PHYSIOL & CELL BIOL,DAVIS,CA 95616. UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,MARINE & FRESHWATER BIOMED SCI CTR,NIEHS,MIAMI,FL 33149. UNIV CALIF DAVIS,DEPT ENVIRONM TOXICOL,DAVIS,CA 95616. FU FDA HHS [NA 37FD0078]; NIEHS NIH HHS [ES05705, ES07685] NR 27 TC 24 Z9 26 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 15 PY 1997 VL 343 IS 2 BP 149 EP 156 DI 10.1006/abbi.1997.0149 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XL431 UT WOS:A1997XL43100001 PM 9224724 ER PT J AU Morales, TI AF Morales, TI TI The role and content of endogenous insulin-like growth factor-binding proteins in bovine articular cartilage SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE insulin-like growth factors (IGFs); insulin-like growth factor binding proteins (IGF-BPs); transforming growth factor-beta (TGF-beta); proteoglycan synthesis; articular cartilage ID FACTOR-BETA; CHONDROCYTES; PROTEOGLYCANS; METABOLISM; CULTURES; INVITRO; ANALOGS; CELLS; BASAL AB Previous work identified insulin-like growth factor (IGF)-binding proteins (IGF-BPs) in chondrocyte culture fluids, but the relationship of these proteins to the composition of intact cartilage was not established. The aim of this work was to analyze the IGF-BP system resident in bovine articular cartilage and to examine its role in IGF-1-regulated proteoglycan (PG) metabolism. Protein extracts of freshly dissected or cultured cartilage slices were analyzed by I-125-IGF-2 ligand blotting, Fresh tissue and basal cultured samples (serum-free) from nine animals, aged fetal to adult, contained two major IGF-BPs of similar to 31,000 and 24,000-21,500 M-r, with the latter doublet being dominant. The 31,000 M-r, protein was identified as IGF-BP-2 by specific immunoreactivity with two polyclonal antibodies, and the 24,000-21,500 M-r doublet was identified as IGF-BP-6 by reactivity with a specific polyclonal antibody and by marked preferential affinity for IGF-2 over IGF-1 by ligand blotting. Treatment of the cartilage cultures with 10 ng/ml transforming growth factor-beta (TGF-beta 1) for 1 week led to an accumulation of IGF-BP-2, while IGF-BP-6 was unchanged (ligand blots, n = 6 animals), IGF-1 had a similar but much less pronounced effect. The IGF-BP increase following TG;F-P treatment, quantified by charcoal assay, was on average 6-fold, while total protein increased only 1.2-fold (n = 4). By contrast, IGF-1 (10 ng/ml) increased IGF-BP by <2-fold (n = 4), and retinoic acid, at 1 x 10(-8) M was not effective (n = 3), As before, 10 ng/ml TGP-P or IGF-1 increased proteoglycan synthesis and maintained its homeostasis. IGF-1 analogs with reduced affinity for the IGF-BPs were tested. The effect of an A-chain analog (Thr(49), Ser(50), IIe(51)) on PG synthesis was comparable to that of IGF-1, even though the analog had one-half of the IGF-1 affinity for the type I IGF receptor. A B-chain analog, with one-third the receptor affinity of IGF-I, promoted an average 2-fold higher PG synthesis in the linear response range to concentration. Thus, in relation to their respective affinities for the IGF-type I receptor, both IGF analogs were more effective than native IGF-1, These results suggest that an overall effect of the endogenous IGF-BP activity in articular cartilage under the test conditions is the inhibition of IGF-1-stimulated proteoglycan can synthesis. (C) 1997 Academic Press. C1 NIDR,OFF SCI DIRECTOR,CARTILAGE METAB PROGRAM,NIH,BETHESDA,MD 20892. NR 29 TC 50 Z9 51 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 15 PY 1997 VL 343 IS 2 BP 164 EP 172 DI 10.1006/abbi.1997.0166 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA XL431 UT WOS:A1997XL43100003 PM 9224726 ER PT J AU Chittum, HS Baek, HJ Diamond, AM FernandezSalguero, P Gonzalez, F Ohama, T Hatfield, DL Kuehn, M Lee, BJ AF Chittum, HS Baek, HJ Diamond, AM FernandezSalguero, P Gonzalez, F Ohama, T Hatfield, DL Kuehn, M Lee, BJ TI Selenocysteine tRNA([Ser]Sec) levels and selenium-dependent glutathione peroxidase activity in mouse embryonic stem cells heterozygous for a targeted mutation in the tRNA[(Ser]Sec) gene SO BIOCHEMISTRY LA English DT Article ID TRANSFER-RNAS; TRANSFER RNASEC; MAMMALIAN-CELLS; ANTICODON; MICE; DISRUPTION; RECEPTOR; TRSP AB To investigate the effect of a reduced level of selenocysteine (Sec) tRNA([Ser]Sec) in selenoprotein biosynthesis, two mouse embryonic stem (ES) cell lines heterozygous for the corresponding gene were generated by homologous recombination of the host genome with targeting vectors encoding a deleted or a disrupted tRNA([Ser]Sec) gene, The presence of a single functional gene in ES cells afforded us an opportunity to determine directly in the cell line the effect of reduced gene dosage on (1) the levels of the Sec tRNA([Ser]Sec) population, (2) the distributions of the isoacceptors within the Sec tRNA population, and (3) selenoprotein biosynthesis. We therefore determined the amounts and distributions of the two major tRNA([Ser]Sec) isoacceptors, designated mcm(5)U and mcm(5)Um, within the Sec tRNA population and determined the activity of the anti-oxidant, selenium-containing glutathione peroxidase (GPx) in the heterozygotes and in wild type cells grown in media with and without added selenium, The level of the Sec tRNA([Ser]Sec) population in the heterozygotes was approximately 60% of that of wild type cells grown in media under normal conditions, while the ratio of the mcmU isoacceptor in wild type vs mutant cells was approximately 2:1 and of the mcmUm isoacceptor approximately 1:1, In the presence of media supplemented with selenium, the Sec tRNA([Ser]Sec) population increased about 20% in wild type cells and virtually not all in heterozygous cells, and the level of the Sec tRNA([Ser]Sec) population was, therefore, approximately 50% of that of wild type cells, GPx activity was indistinguishable among these cell lines in either selenium-supplemented or unsupplemented media, indicating that the resultant changes in tRNA([Ser]Sec) levels did not have a measurable effect on GPx biosynthesis. C1 SEOUL NATL UNIV,INST MOL BIOL & GENET,MOL GENET LAB,SEOUL 151742,SOUTH KOREA. NCI,SECT MOL BIOL SELENIUM,LAB BASIC RES,LAB METAB,EXPT IMMUNOL BRANCH,DIV BASIC SCI,NIH,BETHESDA,MD 20892. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. RI Kuehn, Michael/A-4573-2014; OI Kuehn, Michael/0000-0002-7703-9160; Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 26 TC 13 Z9 13 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 JUL 15 PY 1997 VL 36 IS 28 BP 8634 EP 8639 DI 10.1021/bi970608t PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XK856 UT WOS:A1997XK85600025 PM 9214310 ER PT J AU Pickworth, WB Fant, RV Butschky, MF Goffman, AL Henningfield, JE AF Pickworth, WB Fant, RV Butschky, MF Goffman, AL Henningfield, JE TI Evaluation of cranial electrostimulation therapy on short-term smoking cessation SO BIOLOGICAL PSYCHIATRY LA English DT Article DE cranial electrostimulation; tobacco withdrawal; smoking cessation ID OPIATE ABSTINENCE SYNDROME; ELECTRICAL-STIMULATION; TOBACCO WITHDRAWAL; NICOTINE; SYMPTOMS; ANALGESIA AB The effect of cranial electrical stimulation (CES) on short-term smoking cessation were evaluated in a double-blind study of cigarette smokers who wished to stop smoking. Subjects were randomly assigned to a CES- (n = 51) or a sham-treated group (n = 50). On 5 consecutive days subjects received CES treatments (30-mu A, 2-mesc, 10-Hz pulsed signal) or no electrical current (sham). There were no significant differences between groups on daily cigarettes smoked, exhaled carbon monoxide, urinary continine levels, treatment retention, smoking urges, or total tobacco withdrawal scores, although subjects in the CES group had less cigarette craving and anxiety during the first 2 experimental days. The ineffectiveness of CES to reduce withdrawal symptoms and facilitate smoking cessation are similar to results of other clinical studies of CES in drug dependence, although positive effects of CES in animal studies have been reported. (C) 1997 Society of Biological Psychiatry. RP Pickworth, WB (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 19 TC 12 Z9 12 U1 0 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 JUL 15 PY 1997 VL 42 IS 2 BP 116 EP 121 DI 10.1016/S0006-3223(96)00294-6 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XG238 UT WOS:A1997XG23800006 PM 9209728 ER PT J AU Schwartz, PJ Rosenthal, NE Turner, EH Drake, CL Liberty, V Wehr, TA AF Schwartz, PJ Rosenthal, NE Turner, EH Drake, CL Liberty, V Wehr, TA TI Seasonal variation in core temperature regulation during sleep in patients with winter seasonal affective disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE body temperature; seasonal affective disorder; seasons; depression; skin temperature; light; circadian rhythm; thermoregulation ID BODY-TEMPERATURE; SYRIAN-HAMSTERS; CIRCADIAN-RHYTHM; LIGHT TREATMENT; BRAIN; DEPRESSION; HYPERTHERMIA; HUMANS; STATES; PHASE AB Nocturnal core temperature during sleep is elevated during depression compared with remission in nonseasonally depressed patients. Similarly, nocturnal core temperature is higher during winter depression compared with remission induced by light treatment in seasonal affective disorder (SAD) patients. We investigated whether nocturnal core temperature in SAD patients naturally becomes lower in summer (during remission) compared with winter (during depression). Twenty-four-hour core temperature profiles were obtained in winter and summer in 22 SAD patients and 22 controls, The nocturnal core temperature minima were fewer in summer compared with winter in SAD patients (p < .005), but not controls (p > .4). The seasonal charges in nocturnal core temperatures in SAD patients may reflect a unique physiological responsiveness of SAD patients to the change of seasons, and may be intimately related to the seasonal disturbances of mood and energy that are characteristic of SAD. (C) 1997 Society of Biological Psychiatry. RP Schwartz, PJ (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,RM 4S-239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 41 TC 18 Z9 18 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 1997 VL 42 IS 2 BP 122 EP 131 DI 10.1016/S0006-3223(96)00332-0 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XG238 UT WOS:A1997XG23800007 PM 9209729 ER PT J AU Sconocchia, G Titus, JA Segal, DM AF Sconocchia, G Titus, JA Segal, DM TI Signaling pathways regulating CD44-dependent cytolysis in natural killer cells SO BLOOD LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; PROTEIN-KINASE-C; PHOSPHATIDYLINOSITOL 3-KINASE; MEDIATED CYTOTOXICITY; EXTRACELLULAR-MATRIX; CONJUGATE FORMATION; CYTOPLASMIC DOMAIN; GLYCOPROTEIN CD44; ACTIVATION; VARIANT AB CD44 is a cytotoxic triggering molecule on activated, but not fresh natural killer (NK) cells. In the current study, metabolic pathways used in CD44-directed lysis (CD44DL) were examined using activated human NK cells as effecters, We found that CD44 expressed by activated NK cells was indistinguishable in isoform and molecular weight from CD44 on unactivated cells. However, de novo protein expression was required for the induction of CD44DL, suggesting that activated NK cells contain proteins not present in fresh NK cells that couple CD44 to the lytic machinery. Concanimycin A, a selective inhibitor of perforin-based cytolysis, totally blocked CD44DL, natural cytototoxicity, and antibody-dependent cell-mediated cytolysis (ADCC). Moreover, studies in which kinase inhibitors were added during the effector phase of lysis indicated that protein-tyrosine and ser/thr kinases were required for all three cytolytic activities and that protein kinase C played a nonessential role in lysis. By contrast, wortmannin totally inhibited CD44DL, but failed to block natural cytotoxicity and only partially blocked ADCC, suggesting that phosphatidylinositol 3-kinase (PI 3-kinase) is required at an early, receptor-specific stage of CD44DL, Finally, cytochalasin B enhanced CD44DL, but not ADCC, indicating that CD44DL is modulated by actin polymerization. Taken together, our data suggest that CD44 in NK cells inter acts with proteins induced during interleukin-2 activation in a triggering pathway that induces perforin release, requires PI 3-kinase, and is modulated by the cytoskeleton. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 55 TC 31 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1997 VL 90 IS 2 BP 716 EP 725 PG 10 WC Hematology SC Hematology GA XL774 UT WOS:A1997XL77400025 PM 9226172 ER PT J AU Yang, YL Hosaka, N Pahwa, S AF Yang, YL Hosaka, N Pahwa, S TI Downregulation of increased CD95 (APO-1/Fas) ligand in T cells from human immunodeficiency virus-type 1-infected children after antiretroviral therapy - Response SO BLOOD LA English DT Letter C1 NYU,N SHORE UNIV HOSP,SCH MED,DEPT PEDIAT,MANHASSET,NY. RP Yang, YL (reprint author), NCI,LAB IMMUNE CELL BIOL,NIH,BETHESDA,MD 20892, USA. NR 6 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 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1997 VL 90 IS 2 BP 887 EP 888 PG 2 WC Hematology SC Hematology GA XL774 UT WOS:A1997XL77400044 ER PT J AU McKneally, MF Dickens, BM Meslin, EM Singer, PA AF McKneally, MF Dickens, BM Meslin, EM Singer, PA TI Bioethics for clinicians .13. Resource allocation SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID PSYCHOSOCIAL EVALUATION; TRANSPLANT CANDIDATES; COST-EFFECTIVENESS; CRITERIA; OUTCOMES; OREGON; HEART AB QUESTIONS OF RESOURCE ALLOCATION can pose practical and ethical dilemmas for clinicians. In the Aristotelian conception of distributive justice, the unequal allocation of a scarce resource may be justified by morally relevant factors such as need or likelihood of benefit. Even using these criteria, it can be difficult to reconcile completing claims to determine which patients should be given priority. To what extent the physician's fiduciary duty toward a patient should supersede the interests of other patients and society as a whole is also a matter of controversy. Although the courts have been reluctant to become involved in allocation decisions in health care, they expect physicians to show allegiance to their patients regardless of budgetary concerns. The allocation of resources on the basis of clinically irrelevant factors such as religion or sexual orientation is prohibited. Clear, fair and publicly acceptable institutional and professional policies can help to ensure that resource allocation decisions are transparent and defensible. C1 TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA. NIH,ETH LEGAL & SOCIAL IMPLICAT RES PROGRAM,NATL HUMAN GENOME RES INST,BETHESDA,MD. UNIV TORONTO,SUN LIFE CHAIR BIOETH,TORONTO,ON,CANADA. UNIV TORONTO,JOINT CTR BIOETH,TORONTO,ON,CANADA. NR 24 TC 42 Z9 42 U1 0 U2 1 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUL 15 PY 1997 VL 157 IS 2 BP 163 EP 167 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA XL710 UT WOS:A1997XL71000028 PM 9238146 ER PT J AU Thompson, FH Taetle, R Trent, JM Liu, Y MasseyBrown, K Scott, KM Weinstein, RS Emerson, JC Alberts, DS Nelson, MA AF Thompson, FH Taetle, R Trent, JM Liu, Y MasseyBrown, K Scott, KM Weinstein, RS Emerson, JC Alberts, DS Nelson, MA TI Band 1p36 abnormalities and t(1;17) in ovarian carcinoma SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID NEUROBLASTOMA; HETEROZYGOSITY; TRANSLOCATION; CLUSTER; GENE AB In a series of 128 karyotyped ovarian carcinomas, 42% of cases with chromosome 1 clonal structural abnormalities had breaks at band 1p36 (usually involving translocations of unknown material). Fluorescent in situ hybridization (FISH) studies using combinations of 1 centromere and 1p36.3-specific probes (16 cases) or I centromeric and 17 whole-chromosome paint probes (11 cases with 1p+) revealed a trend toward deletion of 1pter relative to 1 centromere (63%); intratumor heterogeneity; and the origin of 1p+ in 3/11 cases (27%) from chromosome 17 [t(1;17)(p36;?)]. The frequency of this specific breakpoint and its involvement in recurrent translocations suggest that these regions are loci for genes important in the pathogenesis of a subset of sporadic ovarian carcinomas. (C) Elsevier Science Inc., 1997. C1 UNIV ARIZONA,COLL MED,ARIZONA CANC CTR,ONCOL MOL LAB,TUCSON,AZ 85724. UNIV ARIZONA,COLL MED,DEPT PATHOL,TUCSON,AZ 85721. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. FU NCI NIH HHS [CA-23074, CA-41183, R29CA70145-01] NR 16 TC 28 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUL 15 PY 1997 VL 96 IS 2 BP 106 EP 110 DI 10.1016/S0165-4608(96)00307-X PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA XH472 UT WOS:A1997XH47200003 PM 9216715 ER PT J AU Lin, T Trent, JM Milliken, D Shimm, DS Donaldson, R Hill, AB AF Lin, T Trent, JM Milliken, D Shimm, DS Donaldson, R Hill, AB TI Increased frequency of P-glycoprotein gene amplification in colchicine-resistant rat-1 clones transformed by v-src SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID ROUS-SARCOMA VIRUS; WILD-TYPE P53; CELL-LINES; HUMAN FIBROBLASTS; DNA; EXPRESSION; EVOLUTION; PROTEINS; ACTIVATION; VARIANTS AB A rat fibroblast cell line (Rat-1) carrying a temperature-sensitive mutation of v-src was used to determine whether inducible cellular transformation altered the ability of cells to amplify the p-glycoprotein gene in response to colchicine selection. Transformed and nontransformed Rat-1 fibroblasts selected under 4 times the LD50 generated the same number of colchicine-resistant colonies. We next examined colchicine-resistant colonies derived from transformed cells and compared them to colchicine-resistant colonies derived from nontransformed cells. When Rat-1 cells were selected at 35 degrees C (transforming temperature), 7 out of 7 clones exhibited a 3- to 5-fold p-glycoprotein gene amplification. These results contrasted to those found at the nontransforming temperature (40 degrees C); none of the 8 colchicine-resistant clones examined had amplified the p-glycoprotein gene. Thus in Rat-1 cells carrying a temperature-sensitive v-src gene, p-glycoprotein gene amplification was observed at a high frequency only in transformed clones selected at the temperature permissive for v-src activity. (C) Elsevier Science Inc., 1997. C1 UNIV ARIZONA,ARIZONA CANC CTR,TUCSON,AZ. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. FU NCI NIH HHS [CA 23074, CA47547] NR 45 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUL 15 PY 1997 VL 96 IS 2 BP 157 EP 165 DI 10.1016/S0165-4608(96)00324-X PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA XH472 UT WOS:A1997XH47200012 PM 9216724 ER PT J AU Sipowicz, MA Amin, S Desai, D Kasprzak, KS Anderson, LM AF Sipowicz, MA Amin, S Desai, D Kasprzak, KS Anderson, LM TI Oxidative DNA damage in tissues of pregnant female mice and fetuses caused by the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) SO CANCER LETTERS LA English DT Article DE oxidative DNA damage; NNK; transplacental exposure; tobacco-specific nitrosamine ID HUMAN-FETAL LIVERS; MATERNAL SMOKING; CHILDHOOD-CANCER; N-NITROSAMINES; EXPRESSION; RISK; CYTOCHROME-P-450; CARCINOGEN; ACTIVATION; MOUSE AB The tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), induces the promutagenic oxidative-damage DNA lesion, 8-oxo-2'-deoxyguanosine (8-oxo-dG), in adult animals. To investigate whether this alteration occurs in DNA after transplacental exposure, pregnant Swiss mice were administered single or multiple doses of NNK. The 8-oxo-dG was quantified in placenta, and maternal and fetal tissues. In maternal lungs, single and multiple doses of NNK significantly increased levels of 8-oxo-dG by 23% and 32%, respectively. In maternal liver, a significant 38% increase was observed after multiple dose treatment. In the fetuses, a significant 45% increase in 8-oxo-dG levels was observed in liver after multiple doses of NNK. This is the first demonstration of oxidative DNA damage after transplacental exposure to NNK, and supports the concept of maternal smoking as a contributor to the development of childhood cancer. (C) 1997 Elsevier Science Ireland Ltd. C1 AMER HLTH FDN,VALHALLA,NY 10595. RP Sipowicz, MA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,COMPARAT CARCINOGENESIS LAB,BLDG 538,RM 205,FREDERICK,MD 21702, USA. FU NCI NIH HHS [CA-17613] NR 32 TC 24 Z9 25 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 15 PY 1997 VL 117 IS 1 BP 87 EP 91 DI 10.1016/S0304-3835(97)00208-5 PG 5 WC Oncology SC Oncology GA XK319 UT WOS:A1997XK31900013 PM 9233836 ER PT J AU Andreola, F FernandezSalguero, PM Chiantore, MV Petkovich, MP Gonzalez, FJ De Luca, LM AF Andreola, F FernandezSalguero, PM Chiantore, MV Petkovich, MP Gonzalez, FJ De Luca, LM TI Aryl hydrocarbon receptor knockout mice (AHR(-/-)) exhibit liver retinoid accumulation and reduced retinoic acid metabolism SO CANCER RESEARCH LA English DT Article ID VITAMIN-A; BINDING; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; INHIBITION; TISSUES; RAT AB Livers from aryl hydrocarbon receptor-null mice showed a 3-fold increase in retinoids and a 65% decrease in retinoic acid metabolism. Levels of expression of the retinoic acid 4-hydroxylase, P450RAI, did not change, whereas cytochrome P4501A2 levels were lower in the null mouse, as shown earlier; however, this enzyme was found not to be active toward retinoic acid. These data suggest that aryl hydrocarbon receptor controls retinoic acid catabolism, through modulation of an unidentified target gene. Aldehyde dehydrogenases 1 and 2 were down-regulated markedly in the aryl hydrocarbon receptor-deficient mouse liver, 2,3,7,8-Tetrachlorodibenzo-p-dioxin induced cytochrome P4501A2 but not the aldehyde dehydrogenases in wild-type mice, suggesting that aryl hydrocarbon receptor is not involved directly in the down-regulation of this gene. Transglutaminase II, a retinoic acid-responsive gene product, was increased 2-fold, consistent with the liver fibrosis phenotype observed in the null mice. These findings suggest a molecular connection between xenobiotic-activated receptor signaling and retinoid homeostasis. C1 NCI, LCCTP, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. QUEENS UNIV, CANC RES LABS, KINGSTON, ON K7L 3N6, CANADA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 25 TC 91 Z9 95 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1997 VL 57 IS 14 BP 2835 EP 2838 PG 4 WC Oncology SC Oncology GA XL162 UT WOS:A1997XL16200005 PM 9230184 ER PT J AU Rothman, N Smith, MT Hayes, RB Traver, RD Hoener, BA Campleman, S Li, GL Dosemeci, M Linet, M Zhang, LP Xi, LQ Wacholder, S Lu, W Meyer, KB TitenkoHolland, N Stewart, JT Yin, SN Ross, D AF Rothman, N Smith, MT Hayes, RB Traver, RD Hoener, BA Campleman, S Li, GL Dosemeci, M Linet, M Zhang, LP Xi, LQ Wacholder, S Lu, W Meyer, KB TitenkoHolland, N Stewart, JT Yin, SN Ross, D TI Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQ01 C-609->T mutation and rapid fractional excretion of chlorzoxazone SO CANCER RESEARCH LA English DT Article ID GENETIC POLYMORPHISMS; 5'-FLANKING REGION; HUMAN CYP2E1; METABOLISM; P450IIE1; EXPOSURE; WORKERS; IDENTIFICATION; VARIABILITY; EXPRESSION AB Benzene is a ubiquitous occupational hematotoxin and leukemogen, but people vary in their response to this toxic agent, To evaluate the impact of interindividual variation in enzymes that activate (i.e., CYP2E1) and detoxify (i.e., NQO1) benzene and its metabolites, we carried out a case-control study in Shanghai, China, of occupational benzene poisoning (BP; i.e., hematotoxicity), which we show is itself strongly associated with subsequent development of acute nonlymphocytic leukemia and the related myelodysplastic syndromes (relative risk, 70.6; 95% confidence interval, 11.4-439.3). CYP2E1 and NQO1 genotypes were determined by PCR-RFLP, and CYP2E1 enzymatic activity was estimated by the fractional excretion of chlorzoxazone (fe(6-OH)) for 50 cases of BP and 50 controls, Subjects with both a rapid fe6--OH and two copies of the NQO1 C-609-->T mutation had a 7.6-fold (95% confidence interval, 1.8-31.2) increased risk of BP compared to subjects with a slow fe(6-OH) who carried one or two wild-type NQO1 alleles, In contrast, the CYP2E1 PstI/RsaI polymorphism did not influence BP risk. This is the first report that provides evidence of human susceptibility to benzene-related disease. Further evaluation of susceptibility for hematotoxicity and hematological malignancy among workers with a history of occupational exposure to benzene is warranted. C1 UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. UNIV COLORADO,HLTH SCI CTR,SCH PHARM,DENVER,CO 80262. UNIV CALIF SAN FRANCISCO,SCH PHARM,SAN FRANCISCO,CA 94143. CHINESE ACAD PREVENT MED,BEIJING,PEOPLES R CHINA. SHANGHAI HYG & ANTIEPIDEM CTR,SHANGHAI,PEOPLES R CHINA. UNIV GEORGIA,COLL PHARM,ATHENS,GA 30602. RP Rothman, N (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EPN 418,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [P42ES04705] NR 35 TC 216 Z9 236 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1997 VL 57 IS 14 BP 2839 EP 2842 PG 4 WC Oncology SC Oncology GA XL162 UT WOS:A1997XL16200006 PM 9230185 ER PT J AU Hursting, SD Perkins, SN Brown, CC Haines, DC Phang, JM AF Hursting, SD Perkins, SN Brown, CC Haines, DC Phang, JM TI Calorie restriction induces a p53-independent delay of spontaneous carcinogenesis in p53-deficient and wild-type mice SO CANCER RESEARCH LA English DT Article ID SPONTANEOUS TUMORIGENESIS; P53 AB We reported previously that calorie restriction (CR) delays spontaneous carcinogenesis in p53-deficient (p53(-/-)) mice, suggesting that CR modulates carcinogenesis by p53-independent mechanisms, To further evaluate the role of p53, we monitored tumor development in p53(-/-) and wild-type (p53(+/+)) mice fed ad libitum (AL) or a CR regimen (60% of AL calorie intake), CR delayed tumor mortality in p53(-/-) and p53(+/+) mice (mean time to death, 169 and 648 days, respectively) relative to AL feeding (104 and 470 days). The estimated age-specific cancer death rate AL:CR ratios were 4.3 for p53(-/-) mice and 4.4 for p53(+/+) mice, Thus, despite the accelerated onset of carcinogenesis in p53(-/-) mice, the tumor-delaying effect of CR was similar in the two genotypes. C1 NCI,LAB NUTR & MOL REGULAT,DIV BASIC SCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. SCI APPLICAT INT CORP,FREDERICK CANC RES & DEV CTR,PATHOL HISTOTECHNOL LAB,FREDERICK,MD 21702. NCI,BIOMETRY BRANCH,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA16672] NR 15 TC 52 Z9 53 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1997 VL 57 IS 14 BP 2843 EP 2846 PG 4 WC Oncology SC Oncology GA XL162 UT WOS:A1997XL16200007 PM 9230186 ER PT J AU Chang, J Park, K Bang, YJ Kim, WS Kim, D Kim, SJ AF Chang, J Park, K Bang, YJ Kim, WS Kim, D Kim, SJ TI Expression of transforming growth factor beta type II receptor reduces tumorigenicity in human gastric cancer cells SO CANCER RESEARCH LA English DT Article ID TGF-BETA; MICROSATELLITE INSTABILITY; GENE; COLON; INHIBITION; MUTATION; CLONING; COMPLEX; KINASE AB Expression of transforming growth factor beta (TGF-beta) receptor type II (RII) is required for the growth-inhibitory effects of TGF-beta on proliferating epithelial cells, TGF-beta RII mutations have been identified in a broad spectrum of human epithelial malignancies, including colon and gastric cancers, and are highly correlated with development of TGF-beta resistance in cell lines derived from these tumors, In this study, the role of TGF-beta RII in regulating the tumorigenic potential of the SNU-638 human gastric cancer cell line was investigated by infecting these cells with retroviral construct (MFG) expressing TGF-beta RII, The SNU-638 cell line displays the DNA replication error phenotype and encodes a truncated, inactive TGF-beta RII protein, Infection of these cells with retroviral constructs expressing wild-type TGF-beta RII led to significant increases in TGF-beta RII mRNA and protein expression, These cells responded to exogenous TGF-beta with reduced proliferation compared to that of control cells infected with retroviral vector expressing chloramphenicol acetyltranferase. Addition of TGF-beta-neutralizing antibodies led to increased proliferation of wild-type TGF-beta RII-expressing SNU-638 cells but had no effect on control cells, The latter finding suggests that TGF-beta acts in an autocrine fashion to inhibit cell proliferation in SNU-638 cells, When transplanted into athymic nude mice, wild-type TGF-beta RII-expressing SNU-638 cells showed decreased and delayed tumorigenicity compared with control cells, This study suggests a strong association between the expression of wild-type TGF-beta RII and the degree of malignancy in human gastric cancer cells. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. SUNGKYUNKWAN UNIV,COLL MED,DEPT MED,DIV HEMATOL ONCOL,SEOUL,SOUTH KOREA. SUNGKYUNKWAN UNIV,COLL MED,SAMSUNG MED CTR,DEPT MED,DIV HEMATOL ONCOL,SEOUL,SOUTH KOREA. SEOUL NATL UNIV,COLL MED,CANC RES CTR,SEOUL,SOUTH KOREA. RI Bang, Yung Jue/J-2759-2012 NR 21 TC 80 Z9 89 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1997 VL 57 IS 14 BP 2856 EP 2859 PG 4 WC Oncology SC Oncology GA XL162 UT WOS:A1997XL16200010 PM 9230189 ER PT J AU Wang, JX Wang, M Liu, JM AF Wang, JX Wang, M Liu, JM TI Transformation properties of the ETO gene, fusion partner in t(8:21) leukemias SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TRANSCRIPTIONAL ACTIVATION; ZINC FINGERS; AML1 GENE; IDENTIFICATION; CELLS; DIFFERENTIATION; TRANSLOCATION; BREAKPOINTS; DOMAINS AB The (8;21)(q22;q22) translocation, reported in 40% of M2-subtype acute myeloid leukemias (AMLs), is the second-most frequently observed example of a nonrandom genetic alteration associated with AML. Juxtaposition of the AML1 gene on chromosome 21 to the ETO gene on chromosome 8 fuses the NH2-terminal portion of AML1 to near-full length ETO, creating AML1/ETO. Previous work has been focused on perturbation of AML1 gene function by the chimeric fusion protein as a mechanism of leukemogenesis. Here, we demonstrate that ETO itself has transforming properties. Ectopic ETO expression in NIH/3T3 cells led to foci of transformation and colony growth in soft agar. ETO-expressing cells grew to higher saturation densities and induced tumors following injection into irradiated and splenectomized nude mice. Our data suggests that ETO may play an important role in the leukemic transforming potential of the AML1/ETO fusion protein. C1 NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. NIDDKD,MOL HEMATOL SECT,BIOL CHEM LAB,BETHESDA,MD 20892. NR 29 TC 15 Z9 18 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1997 VL 57 IS 14 BP 2951 EP 2955 PG 5 WC Oncology SC Oncology GA XL162 UT WOS:A1997XL16200028 PM 9230207 ER PT J AU Bennett, SE Umar, A Oshima, J Monnat, RJ Kunkel, TA AF Bennett, SE Umar, A Oshima, J Monnat, RJ Kunkel, TA TI Mismatch repair in extracts of Werner syndrome cell lines SO CANCER RESEARCH LA English DT Article ID VARIEGATED TRANSLOCATION MOSAICISM; SKIN FIBROBLASTS; SYNDROME REGION; DNA HELICASE; IMMORTALIZATION; CHROMOSOME-8; MARKERS; HOMOLOG; CANCER AB Werner syndrome (WS) is an autosomal recessive disease, the phenotype of which is a caricature of premature aging, WS cells and cell lines display several types of genetic instability, and WS patients have an increased risk of developing cancer, The WS locus (WRN) encodes a protein that shows significant sequence homology to the RecQ family of DNA helicases, Because a DNA helicase may function in DIVA mismatch repair, we examined extracts of WS cell lines for mismatch repair activity, Extracts from four different WS lymphoblastoid cell lines containing different WRN mutations and from three within-pedigree control cell lines were all proficient in mismatch repair, In marked contrast, extracts from three independent WS fibroblastoid cell lines were deficient in repair of base-base and insertion/deletion mismatches, Extracts of one of these lines restored activity to extracts of mismatch repair-deficient tumor cells with defined mutations in hMSH2, hMSH3, hMSH6, hMLH1, or hPMS2. This suggests that the WRN mutation in this fibroblast line is not a dominant negative inhibitor of mismatch repair activity and that the repair defect does not reside in these five known mismatch repair genes, Defective mismatch repair in fibroblastoid but not lymphoblastoid cells is consistent with the possibility that WRN protein could have a cell type- and/or tissue-specific role in mismatch repair. Alternatively, a mutation in WRN could predispose cells to mutations in other genes required for mismatch repair activity, at least one of which could be an unknown gene. C1 NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. NR 43 TC 47 Z9 47 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1997 VL 57 IS 14 BP 2956 EP 2960 PG 5 WC Oncology SC Oncology GA XL162 UT WOS:A1997XL16200029 PM 9230208 ER PT J AU Isaacs, JS Chiao, C Merrick, BA Selkirk, JK Barrett, JC Weissman, BE AF Isaacs, JS Chiao, C Merrick, BA Selkirk, JK Barrett, JC Weissman, BE TI p53-dependent p21 induction following gamma-irradiation without concomitant p53 induction in a human peripheral neuroepithelioma cell line SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; WILD-TYPE P53; HUMAN PAPILLOMAVIRUS TYPE-16; CYCLE CHECKPOINT PATHWAY; DNA-DAMAGING AGENTS; IN-VITRO; P53-INDEPENDENT PATHWAY; NUCLEAR ACCUMULATION; GENE AMPLIFICATION; TRANSFORMED-CELLS AB We previously generated cell hybrids between a derivative of the E6-containing HeLa cell line and a p53 null peripheral neuroepithelonma (PNET) cell line. Although p53 protein from the hybrids was genotypically wild the, it did not demonstrate wild-type behavior, Therefore, in the present study, we introduced wild-type p53 into the PNET parent to investigate whether p53 retained wild-type function within this cell line. Although the p53 null PNET parent lacked detectable p21 protein, introduction of wild-type p53 resulted in a detectable expression of p21 protein in all clones tested, suggestive of mild-type p53 function, In addition, p53 expression was necessary for induction of p21 in response to irradiation, and, furthermore, we show this induction to occur at the transcriptional level. Although introduction of wild-type p53 seems to be responsible for p21 induction, the overall protein levels of p53 were not induced, The involvement of p53 in up-regulating p21 is further substantiated by the observation that p21 up-regulation was dependent on the introduction of the wild-type protein, Our results suggest that mild-type p53 is capable of up-regulating p21 in response to DNA damage in the absence of p53 induction. C1 UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599. NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA44470] NR 69 TC 18 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1997 VL 57 IS 14 BP 2986 EP 2992 PG 7 WC Oncology SC Oncology GA XL162 UT WOS:A1997XL16200034 PM 9230213 ER PT J AU Smith, LM Birrer, MJ Stampfer, MR Brown, PH AF Smith, LM Birrer, MJ Stampfer, MR Brown, PH TI Breast cancer cells have lower activating protein 1 transcription factor activity than normal mammary epithelial cells SO CANCER RESEARCH LA English DT Article ID SIGNAL TRANSDUCTION PATHWAYS; EPIDERMAL GROWTH-FACTOR; C-JUN; FOS GENE; INDUCED TRANSFORMATION; BINDING AFFINITIES; PHORBOL ESTERS; AP-1 ACTIVITY; DNA-BINDING; EXPRESSION AB To determine whether normal breast cells have different levels of activating protein 1 (AP-1) expression and activation relative to breast cancer cells, we have compared the level of c-Jun and c-Fos expression and AP-1 activity in human mammary epithelial cells (HMECs) at different stages of transformation (normal proliferating (HMECs, immortal HMECs, oncogene-transformed HMECs, and breast cancer cell lines). These studies demonstrated that normal and immortal HMECs have a high basal level of expression of cJun and cFos and higher AP-1 DNA-binding and transcriptional activating activities than do oncogene-transformed HMECs or human breast cancer cells, with a gradual decrease in AP-1 transactivating activity as cells progress through the carcinogenesis pathway (normal > immortal > oncogene-transformed > cancer cell lines). The AP-1 activity in normal or immortal cells was not modulated by growth factor supplementation or oncogene overexpression, as it is in breast cancer cells. However, the addition of suramin, a nonspecific growth factor antagonist, did inhibit. AP-1 in these HMECs, suggesting that this high level of AP-1 present in normal HMECs mag be due to autocrine stimulation of growth factor pathways. The differences in AP-1 activity in normal and malignant breast cells may indicate that normal cells are more dependent on AP-1-mediated signals for their growth than are breast cancer cells. C1 UNIV TEXAS,HLTH SCI CTR,DIV MED ONCOL,DEPT MED,SAN ANTONIO,TX 78284. NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD 20850. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,BERKELEY,CA 94720. FU NCI NIH HHS [CA-24844, Z01 CN000179, 5P50 CA-58183] NR 51 TC 28 Z9 28 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1997 VL 57 IS 14 BP 3046 EP 3054 PG 9 WC Oncology SC Oncology GA XL162 UT WOS:A1997XL16200042 PM 9230221 ER PT J AU Harrell, RL Rajanayagam, S Doanes, AM Guzman, RJ Hirschowitz, EA Crystal, RG Epstein, SE Finkel, T AF Harrell, RL Rajanayagam, S Doanes, AM Guzman, RJ Hirschowitz, EA Crystal, RG Epstein, SE Finkel, T TI Inhibition of vascular smooth muscle cell proliferation and neointimal accumulation by adenovirus-mediated gene transfer of cytosine deaminase SO CIRCULATION LA English DT Article DE angioplasty; adenoviruses; muscles, smooth ID RAT CAROTID-ARTERY; THYMIDINE KINASE GENE; IN-VIVO; BALLOON ANGIOPLASTY; 5-FLUOROCYTOSINE; SENSITIVITY; THERAPY; INJURY; TUMOR AB Background Restenosis remains a significant problem after balloon angioplasty. Previous studies have demonstrated that recombinant adenoviruses are efficient vectors for gene transfer to the arterial wall and can be used to inhibit the proliferative aspect of restenosis. We sought to extend these observations using AdCMV.CD, an adenovirus that encodes cytosine deaminase (CD) and is capable of metabolizing 5-fluorocytosine (5-FC) to 5-fluorouracil. Methods and Results Infection of vascular smooth muscle cells (VSMC) with AdCMV.CD increases by two to three orders of magnitude the growth-inhibitory effects of 5-FC. The degree of VSMC inhibition in vitro was a function of 5-FC concentration and the level of CD expression. Cells infected with AdCMV.CD exhibited a profound bystander effect on the growth of neighboring cells, which did not require direct cell-to-cell contact. The predominant effect of AdCMV.CD on growth of VSMC appeared to be cytostatic, not cytotoxic. Assessment of this strategy in a rabbit femoral artery model of balloon-induced injury demonstrated that compared with animals in either of two control groups, animals treated with the active combination of infection with AdCMV.CD and 1-week treatment with parenteral 5-FC had a significant reduction at 30 days in the neointimal-to-medial ratio. Conclusions Our results suggest that adenovirus-mediated gene transfer of CD along with 5-FC administration may be a useful strategy to treat the proliferative aspects of restenosis. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE,NEW YORK,NY 10021. NR 23 TC 54 Z9 57 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 JUL 15 PY 1997 VL 96 IS 2 BP 621 EP 627 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA XM003 UT WOS:A1997XM00300043 PM 9244235 ER PT J AU Phillips, AC Bates, S Ryan, KM Helin, K Vousden, KH AF Phillips, AC Bates, S Ryan, KM Helin, K Vousden, KH TI Induction of DNA synthesis and apoptosis are separable functions of E2F-1 SO GENES & DEVELOPMENT LA English DT Article DE E2F; apoptosis; cell cycle; p53 ID TRANSCRIPTION FACTOR E2F-1; CELL-CYCLE CONTROL; S-PHASE ENTRY; RETINOBLASTOMA GENE-PRODUCT; NEGATIVE REGULATION; PROTEIN; EXPRESSION; PROMOTER; BINDING; GROWTH AB The family of E2F transcription factors have an essential role in mediating cell cycle progression, and recently, one of the E2F protein family, E2F-1, has been shown to participate in the induction of apoptosis. Cooperation between E2F and the p53 tumor suppressor protein in this apoptotic response had led to the suggestion that cell cycle progression induced by E2F-1 expression provides an apoptotic signal when placed in conflict with an arrest to cell cycle progression, such as provided by p53. We show here that although apoptosis is clearly enhanced by p53, E2F-1 can induce significant apoptosis in the absence of p53. furthermore, this apoptotic function of E2F-1 is separable from the ability to accelerate entry into DNA synthesis, Analysis of E2F-1 mutants indicates that although DNA-binding is required, transcriptional transactivation is not necessary for the induction of apoptosis by E2F-1, suggesting that it may be mediated through alleviation of E2F-dependent transcriptional repression. These results indicate that E2F-1 can show independent cell cycle progression and apoptotic functions, consistent with its putative role as a tumor suppressor. C1 NCI,ABL,BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. EUROPEAN INST ONCOL,DEPT EXPT ONCOL,I-20141 MILAN,ITALY. NR 49 TC 244 Z9 247 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 15 PY 1997 VL 11 IS 14 BP 1853 EP 1863 DI 10.1101/gad.11.14.1853 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XM835 UT WOS:A1997XM83500008 PM 9242492 ER PT J AU Andersen, B Weinberg, WC Rennekampff, O McEvilly, RJ Bermingham, JR Hooshmand, F Vasilyev, V Hansbrough, JF Pittelkow, MR Yuspa, SH Rosenfeld, MG AF Andersen, B Weinberg, WC Rennekampff, O McEvilly, RJ Bermingham, JR Hooshmand, F Vasilyev, V Hansbrough, JF Pittelkow, MR Yuspa, SH Rosenfeld, MG TI Functions of the POU domain genes Skn-1a/i and Tst-1/Oct-6/SCIP in epidermal differentiation SO GENES & DEVELOPMENT LA English DT Article DE POU; epidermis; differentiation; wound healing ID EXPRESSION; CELLS; PROTEIN; OCT-1; ANTIBODIES; PROMOTER; SURFACE; MICE AB Here we report on investigation of the role of the POU domain genes Skin-1a/i (Skn-1a/i/Epoc/Oct-11) and Testes-1 (Tst-1/Oct-6/SCIP) in epidermis where proliferating basal keratinocytes withdraw from the cell cycle, migrate suprabasally, and terminally differentiate to form a multilayered, stratified epithelium. The expression of the Skn-1a/i and Tst-1 genes is linked to keratinocyte differentiation in vivo and in vitro, whereas the ubiquitous POU domain factor Oct-1 is expressed highly in both proliferating and post-mitotic keratinocytes. Analysis of Skn-1a/i gene-deleted mice reveals that the Skn-1a/i gene modulates the pattern of expression of the terminal differentiation marker loricrin and inhibits expression of genes encoding markers of the epidermal keratinocyte wounding response. Although epidermis from Tst-1 gene-deleted mice develops normally, epidermis from mice deleted for both Skn-1a/i and Tst-1 is hyperplastic and fails to suppress expression of K14 and Spr-1 in suprabasal cells when transplanted onto athymic mice. This suggests that Skn-1a/i and Tst-1 serve redundant functions in epidermis. Therefore, at least two POU domain genes, Skn-1a/i and Tst-1, serve both distinct and overlapping functions to regulate differentiation of epidermal keratinocytes during normal development and wound healing. C1 UNIV CALIF SAN DIEGO, SCH MED, HOWARD HUGHES MED INST, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, DEPT MED, HOWARD HUGHES MED INST, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, DEPT SURG, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, DIV ENDOCRINOL & METAB, LA JOLLA, CA 92037 USA. NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, NIH, BETHESDA, MD 20892 USA. MAYO CLIN & MAYO FDN, DEPT DERMATOL, ROCHESTER, MN 55905 USA. MAYO CLIN & MAYO FDN, DEPT MOL BIOL & BIOCHEM, ROCHESTER, MN 55905 USA. RI Weinberg, Wendy/A-8920-2009 FU NIDDK NIH HHS [DK02411] NR 50 TC 72 Z9 72 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 15 PY 1997 VL 11 IS 14 BP 1873 EP 1884 DI 10.1101/gad.11.14.1873 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA XM835 UT WOS:A1997XM83500010 PM 9242494 ER PT J AU Sugino, H Yoshihara, Y Copeland, NG Gilbert, DJ Jenkins, NA Mori, K AF Sugino, H Yoshihara, Y Copeland, NG Gilbert, DJ Jenkins, NA Mori, K TI Genomic organization and chromosomal localization of the mouse telencephalin gene, a neuronal member of the ICAM family SO GENOMICS LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; DNA-BINDING SPECIFICITY; CELL-ADHESION; IMMUNOGLOBULIN SUPERFAMILY; TRANSCRIPTIONAL ACTIVATOR; MEMBRANE GLYCOPROTEIN; PROTEIN; CLONING; EXPRESSION; PROMOTER AB Telencephalin is a cell adhesion molecule belonging to the immunoglobulin (Ig) superfamily, whose expression is restricted to subsets of neurons in the telencephalon, the most rostral segment of brain. Of all the Ig superfamily molecules so far identified, the structure of telencephalin is most closely related to those of intercellular adhesion molecules (ICAMs)-1 and -3. Here we report the cloning, characterization, and chromosomal localization of the mouse telencephalin gene (Tlcn). The Tlcn gene spanned about 6.3 kb and consisted of 11 exons. A signal peptide and individual nine Ig-like domains of telencephalin were encoded by a single exon, while the transmembrane and cytoplasmic regions were fused in a same exon. The primer extension technique was used to establish that the transcription initiation sites were located 92-95 bp upstream from the ATG start codon. DNA sequencing of the 5'-flanking region revealed the presence of a strong initiator element for TATA-less genes, two CAAT boxes, and numerous potential transcription factor binding sites including four E-box and two N-box sequences. Interspecific backcross analysis demonstrated that the Tlcn gene was mapped in the proximal region of mouse chromosome 9 in close vicinity to the Icam-1 gene, suggesting that Tlcn and Icam-1 are derived from a common ancestral gene by gene duplication. (C) 1997 Academic Press. C1 OSAKA BIOSCI INST,DEPT NEUROSCI,SUITA,OSAKA 565,JAPAN. RIKEN,FRONTIER RES PROGRAM,LAB NEURONAL RECOGNIT MOL,WAKO,SAITAMA 35101,JAPAN. OSAKA MED COLL,DEPT BIOCHEM,TAKATSUKI,OSAKA 569,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Yoshihara, Yoshihiro/N-6481-2015 NR 58 TC 7 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1997 VL 43 IS 2 BP 209 EP 215 DI 10.1006/geno.1997.4812 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XN413 UT WOS:A1997XN41300012 PM 9244438 ER PT J AU Malfroy, L Roth, MP Carrington, M Borot, N Volz, A Ziegler, A Coppin, H AF Malfroy, L Roth, MP Carrington, M Borot, N Volz, A Ziegler, A Coppin, H TI Heterogeneity in rates of recombination in the 6-Mb region telomeric to the human major histocompatibility complex SO GENOMICS LA English DT Article ID FIELD GEL-ELECTROPHORESIS; LINKAGE DISEQUILIBRIUM; GENE; HEMOCHROMATOSIS; MHC; ASSOCIATION; HAPLOTYPES AB Analysis of 784 informative meioses in the CEPH pedigrees revealed a total of 22 recombination events having occurred in the 6-Mb region between D6S265 (70 kb centromeric of HLA-A) and D6S276. These 22 breakpoints were localized with respect to anonymous polymorphic markers, leading to a detailed genetic map of the region telomeric to the human major histocompatibility complex. A nonrandom pattern of recombination was observed throughout this region: the low recombination rate of 0.19% within the 4-Mb interval centromeric to the HLA class I-like candidate gene for hemochromatosis indeed contrasts with the approximate 1% rate observed within the most telomeric two megabases. This reduced rate of recombination may be due to selective constraints depending on environmental factors related to immunity and iron status or to structural variations hampering proper meiotic pairing of homologous sequences. Population data from other human genome segments are now needed to determine whether linkage disequilibrium extending over 4 Mb is unique to this region. (C) 1997 Academic Press. C1 CHU PURPAN,CNRS UPR 8291,CTR IMMUNOPATHOL & GENET HUMAINE,F-31300 TOULOUSE,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. HUMBOLDT UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,INST EXPT ONKOL & TRANSPLANTAT MED,D-14050 BERLIN,GERMANY. RI coppin, helene/G-4326-2013 NR 21 TC 57 Z9 59 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 JUL 15 PY 1997 VL 43 IS 2 BP 226 EP 231 DI 10.1006/geno.1997.4800 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XN413 UT WOS:A1997XN41300015 PM 9244441 ER PT J AU Engelen, JJM Esterling, LE Albrechts, JCM DeteraWadleigh, SD vanEys, GJJM AF Engelen, JJM Esterling, LE Albrechts, JCM DeteraWadleigh, SD vanEys, GJJM TI Assignment of the human gene for smoothelin (SMTN) to chromosome 22q12 by fluorescence in situ hybridization and radiation hybrid mapping SO GENOMICS LA English DT Article ID MUSCLE CELLS; CALPONIN; REGION C1 UNIV LIMBURG,DEPT MOL GENET & CELL BIOL,NL-6200 MD MAASTRICHT,NETHERLANDS. NIMH,UNIT GENE MAPPING & EXPRESS,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. NIDCD,GENET MOL LAB,NIH,BETHESDA,MD 20892. NR 17 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1997 VL 43 IS 2 BP 245 EP 247 DI 10.1006/geno.1997.9999 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA XN413 UT WOS:A1997XN41300019 PM 9244445 ER PT J AU McDiarmid, R Xing, X AF McDiarmid, R Xing, X TI Nonadiabatic coupling of the 3p Rydberg and pi pi* valence states of acetone SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MULTI-PHOTON IONIZATION; CONFIGURATION-INTERACTION; EXCITED-STATES; FORMALDEHYDE; SPECTROSCOPY; ASSIGNMENTS AB The 3p Rydberg region of the spectra of acetone and acetone-d(6) has been studied by resonantly enhanced multiphoton ionization and photoacoustic spectroscopies. Differences between the spectra of cold and room temperature samples, between REMPI and PA spectral measurements, and between the laser power dependences of the different 3p<--(X) over tilde origins have been deduced to arise from a nonadiabatic coupling of the A(1) 3p Rydberg and A(1) pi pi* states of acetone. The coupling is proposed to arise from a seam of conical intersection between these two Al states on the CO stretch-C2CO pyramidalization plane. An analogous seam is proposed to exist between the A(1) 3d Rydberg and A(1) pi pi* states. (C) 1997 American Institute of Physics. RP McDiarmid, R (reprint author), NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 20 TC 10 Z9 10 U1 0 U2 5 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 JUL 15 PY 1997 VL 107 IS 3 BP 675 EP 679 DI 10.1063/1.475152 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA XK179 UT WOS:A1997XK17900001 ER PT J AU Muraro, PA Vergelli, M Kalbus, M Banks, DE Nagle, JW Tranquill, LR Nepom, GT Biddison, WE McFarland, HF Martin, R AF Muraro, PA Vergelli, M Kalbus, M Banks, DE Nagle, JW Tranquill, LR Nepom, GT Biddison, WE McFarland, HF Martin, R TI Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE multiple sclerosis; autoimmune diseases; CD4-positive T lymphocytes; autoantigens; complementarity-determining region ID ANTIGEN-PRESENTING CELLS; CLASS-II MOLECULES; MULTIPLE-SCLEROSIS; AUTOIMMUNE ENCEPHALOMYELITIS; FINE SPECIFICITY; LYMPHOCYTE-T; BETA-CHAIN; HLA-DR; ALLERGIC ENCEPHALOMYELITIS; HEALTHY-INDIVIDUALS AB The pathogenesis of multiple sclerosis (MS) is currently ascribed in part to a T cell-mediated process targeting myelin components. The T cell response to one candidate autoantigen, myelin basic protein (MBP), in the context of HLA-DR15Dw2, has been previously studied in detail, However, the characteristics of cellular immunity in the context of other MS-associated HLA-DR haplotypes are scarcely known, MBP-specific T cell lines (TCL) were generated from HLA-DR4 (B1*0401)-positive MS subjects, Out of 275 MBP-specific TCL, 178 (64.7%) specifically recognized region MBP(111-129), predominantly in the context of DRB1*0401. The major T cell epitope for MBP recognition corresponded to residues MBP(116-123). These TCL expressed disparate profiles of cytokine secretion and cytotoxicity, T cell receptor analysis, on the other hand, revealed a strikingly limited heterogeneity of rearrangements, In contrast to MBP(81-99), which binds with high affinity to HLA-DR15 and is recognized by a diverse T cell repertoire, MBP(111-129) binds weakly to DRB1*0401, suggesting that only high affinity T cell receptors might be able to efficiently engage such unstable MHC/peptide complexes, thus accounting for the T cell receptor restriction we observed, This study provides new insight about MBP recognition and proposes an alternative mechanism for immunodominance of self-antigen T cell epitopes in humans. C1 NINCDS,DNA SEQUENCING FACIL,NIH,BETHESDA,MD 20892. UNIV G DANNUNZIO,SCH MED,DEPT ONCOL & NEUROSCI,I-66100 CHIETI,ITALY. UNIV TUBINGEN,SCH MED,DEPT NEUROL,D-72076 TUBINGEN,GERMANY. VIRGINIA MASON RES CTR,SEATTLE,WA 98101. RP Muraro, PA (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH,BLDG 10,ROOM 5B-16,10 CTR DR,MSC 1400,BETHESDA,MD 20892, USA. OI Muraro, Paolo/0000-0002-3822-1218 NR 73 TC 90 Z9 91 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL 15 PY 1997 VL 100 IS 2 BP 339 EP 349 DI 10.1172/JCI119539 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XN372 UT WOS:A1997XN37200013 PM 9218510 ER PT J AU Gressens, P Marret, S Hill, JM Brenneman, DE Gozes, I Fridkin, M Evrard, P AF Gressens, P Marret, S Hill, JM Brenneman, DE Gozes, I Fridkin, M Evrard, P TI Vasoactive intestinal peptide prevents excitotoxic cell death in the murine developing brain SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE activity-dependent neurotrophic factor; cerebral palsy; ibotenic acid; N-methyl-D-aspartate; vasoactive intestinal peptide ID CYCLASE-ACTIVATING POLYPEPTIDE; CENTRAL-NERVOUS-SYSTEM; CEREBRAL-PALSY; FUNCTIONAL EXPRESSION; NEURONAL SURVIVAL; VIP RECEPTORS; RAT-BRAIN; ANTAGONIST; MOUSE; MAGNESIUM AB Excitotoxic damage may be a critical factor in the formation of brain lesions associated with cerebral palsy. When injected at birth, the glutamatergic analog ibotenate induces mouse brain lesions that strikingly mimic human microgyria. When ibotenate is injected at postnatal day 5, it produces transcortical necrosis and white matter cysts that mimic human perinatal hypoxic-like lesions. Vasoactive intestinal peptide (VIP) has potent growth-related actions and neuroprotective properties that influence mitosis and neuronal survival in culture. The goal of this study was to assess the protective role of VIP against excitotoxic lesions induced by ibotenate in developing mouse brain. VIP cotreatment reduced ibotenate-induced microgyric-like cortical lesions and white matter cysts by up to 77 and 85%, respectively. VIP protective effects were reproduced by a peptide derived from activity-dependent neurotrophic factor (ADNF), a trophic factor released by VIP-stimulated astrocytes, and by stearyl norleucine VIP, a specific VIP agonist that does not activate adenylate cyclase. Neither forskolin, an adenylate cyclase activator, nor pituitary adenylate cyclase-activating peptide, provided VIP-like protection. VIP and neurotrophic analogs, acting through a cAMP-independent mechanism and inducing ADNF release, could represent new avenues in the understanding and prevention of human cerebral palsy. C1 FAC XAVIER BICHAT,F-75019 PARIS,FRANCE. HOP CHARLES NICOLLE,SERV NEONATOL,F-76000 ROUEN,FRANCE. NICHHD,SECT DEV & MOL PHARMACOL,DEV NEUROBIOL LAB,BETHESDA,MD 20892. TEL AVIV UNIV,DEPT CLIN BIOCHEM,IL-69978 TEL AVIV,ISRAEL. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-78100 REHOVOT,ISRAEL. RP Gressens, P (reprint author), HOP ROBERT DEBRE,SERV NEUROPEDIAT,48 BLVD SERURIER,F-75019 PARIS,FRANCE. NR 61 TC 154 Z9 156 U1 0 U2 4 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 JUL 15 PY 1997 VL 100 IS 2 BP 390 EP 397 DI 10.1172/JCI119545 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA XN372 UT WOS:A1997XN37200019 PM 9218516 ER PT J AU Vinitsky, A Anton, LC Snyder, HL Orlowski, M Bennink, JR Yewdell, JW AF Vinitsky, A Anton, LC Snyder, HL Orlowski, M Bennink, JR Yewdell, JW TI The generation of MHC class I associated peptides is only partially inhibited by proteasome inhibitors - Involvement of nonproteasomal cytosolic proteases in antigen processing? SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MULTICATALYTIC PROTEINASE COMPLEX; CHYMOTRYPSIN-LIKE ACTIVITY; TOXIC LYMPHOCYTES-T; HLA-B ANTIGENS; ENDOPLASMIC-RETICULUM; INTERFERON-GAMMA; CELL-LINES; PROTEOLYTIC ACTIVITY; LINKED LMP AB The proteasome is believed to participate in the generation of a large percentage of peptide ligands for MHC class I molecules, This conclusion is based largely on the activities of peptidyl aldehydes that block proteasome activity, We tested the ability of a panel of proteasome inhibitors to affect the generation of MHC class I binding peptides in mouse L929 cells, Included in the panel are peptidyl aldehydes and a microbial product, lactacystin, that blocks proteasome activity in a distinct and more specific manner, Contrary to expectations, proteasome inhibitors failed to block the generation of a large portion of high affinity peptides as inferred by measuring cell surface expression of newly synthesized MHC class I molecules, These findings were confirmed by examining the effects of the inhibitors on the presentation of individual antigenic determinants from endogenously synthesized or exogenously delivered influenza virus proteins, Presentation of peptides derived from exogenous basic polymerase 1, endogenous basic polymerase 1, and nonstructural-l proteins was decreased by inhibitors in a manner consistent with proteasomal involvement, Presentation of peptides derived from endogenous nucleoprotein was not significantly affected by the proteasome inhibitors, while presentation of exogenous hemagglutinin and nucleoprotein was enhanced by the proteasome inhibitors, These data are consistent with the involvement of both proteasomes and nonproteasomal cytosolic proteases in the generation of a significant portion of MHC class I binding peptides. C1 CUNY MT SINAI SCH MED,DEPT PHARMACOL,NEW YORK,NY 10029. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012; Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X FU NIDDK NIH HHS [DK25377] NR 71 TC 90 Z9 92 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 JUL 15 PY 1997 VL 159 IS 2 BP 554 EP 564 PG 11 WC Immunology SC Immunology GA XJ674 UT WOS:A1997XJ67400005 PM 9218569 ER PT J AU Schwartz, GN Liao, F Gress, RE Farber, JM AF Schwartz, GN Liao, F Gress, RE Farber, JM TI Suppressive effects of recombinant human monokine induced by IFN-gamma (rHuMig) chemokine on the number of committed and primitive hemopoietic progenitors in liquid cultures of CD34(+) human bone marrow cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-INDUCIBLE PROTEIN-10; UMBILICAL-CORD BLOOD; COLONY-FORMING CELLS; GROWTH-FACTOR-II; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; LONG-TERM CULTURES; PLATELET FACTOR-IV; FUNCTIONAL-CHARACTERIZATION; HEMATOPOIETIC-CELLS; LIMITING DILUTION AB Studies in this report investigated potential hemopoietic suppressive effects of human monokine induced by IFN-gamma (HuMig), a CXC chemokine that is chemotactic for activated lymphocytes. rHuMig was purified from Trichoplusia ni cells after infection with a recombinant baculovirus. The recombinant protein was added to liquid cultures of CD34(+) human marrow cells stimulated with IL-3 alone or with both IL-3 and either insulin-like growth factor II (ICF-II) or stem cell growth factor (SCF). The number of committed progenitors, colony-forming units for granulocytes and macrophages (CFU-CM), and primitive progenitors, long term culture-initiating cells (LTC-IC) derived from liquid cultures of CD34(+) cells, was determined. rHuMig abrogated the IGF-II-dependent enhancement of CFU-GM and long term culture-initiating cell numbers. Additional studies demonstrated that in liquid cultures of CD34(+) cells both rHuMig and IFN-inducible protein-10, another CXC chemokine that is related to HuMig, inhibited the production or expansion of CFU-CM. For a subset of marrows, rHuMig also abrogated SCF enhancement of CFU-CM numbers in cultures of CD34(+) cells stimulated with both IL-3 and SCF, These studies are the first to demonstrate that rHuMig can act as a negative regulator of in vitro hemopoiesis, that both rHuMig and IP-10 can suppress an increase in the number of committed progenitors from CD34(+) cells, and that chemokines can abrogate hemopoietic stimulatory effects oi IGF-II. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP Schwartz, GN (reprint author), NCI,DEPT EXPTL TRANSPLANTAT & IMMUNOL,MED BRANCH,NIH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 56 TC 19 Z9 20 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 JUL 15 PY 1997 VL 159 IS 2 BP 895 EP 904 PG 10 WC Immunology SC Immunology GA XJ674 UT WOS:A1997XJ67400045 PM 9218609 ER PT J AU Sun, B Rizzo, LV Sun, SH Chan, CC Wiggert, B Wilder, RL Caspi, RR AF Sun, B Rizzo, LV Sun, SH Chan, CC Wiggert, B Wilder, RL Caspi, RR TI Genetic susceptibility to experimental autoimmune uveitis involves more than a predisposition to generate a T helper-1-like or a T helper-2-like response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETINOID-BINDING PROTEIN; FUNCTIONAL-PROPERTIES; IN-VIVO; UVEORETINITIS; EXPRESSION; MICE; DISEASE; MODEL; GAMMA; INTERLEUKIN-2 AB This study examines whether genetic susceptibility vs resistance to experimental autoimmune uveoretinitis (EAU) in mice is associated with dominant type 1 vs type 2 cytokine response profiles. Mice from six strains were immunized with the uveitogenic retinal Ag IRBP. EAU was evaluated by histopathology, As judged by disease scores, three of the strains were susceptible, one was minimally susceptible, and two were resistant. Ag-specific type 1 vs type 2 cytokine responses (protein and/or mRNA) in draining lymph node cells, and IgG2a vs IgG1 Ab isotypes to IRBP, were measured as indicators of Th1-like vs Th2-like responses, respectively, The three susceptible strains (B10.A, C57BL/10, and BALB/k) showed a dominant Th1-like response profile characterized by high IFN-gamma and IL-12p40 (but not IL-4) responses, and a predominance of IgG2a Abs, The minimally susceptible strain (A/J) had an IFN-gamma response detectable only at the mRNA level, but produced predominantly IgG2a Abs, One of the two resistant strains (BALB/c) showed a characteristic Th2-like response with dominant Ag-specific IL-4 and IL-10 responses but no IFN-gamma, and predominantly IgG1 Abs. However, the other resistant strain (AKR) did not show a Th2-dominated response pattern, in that it had low, or no, IL-4 and IL-10 responses, and made predominantly IgG2a Abs to IRBP, These results suggest that whereas a Th1 response is required for susceptibility, resistance is not dependent on a Th2 response pattern. We suggest that regulatory influences other than skewing the response toward the Th2 pathway may be equally effective at conferring genetic resistance to EAU. C1 NEI, IMMUNOL LAB, NIH, BETHESDA, MD 20892 USA. NEI, RETINAL CELL & MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. NIAMSD, ARTHRIT & RHEUMATISM BRANCH, NIH, BETHESDA, MD 20892 USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 41 TC 110 Z9 123 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1997 VL 159 IS 2 BP 1004 EP 1011 PG 8 WC Immunology SC Immunology GA XJ674 UT WOS:A1997XJ67400059 PM 9218623 ER PT J AU Nirenberg, MJ Chan, J Vaughan, RA Uhl, GR Kuhar, MJ Pickel, VM AF Nirenberg, MJ Chan, J Vaughan, RA Uhl, GR Kuhar, MJ Pickel, VM TI Immunogold localization of the dopamine transporter: An ultrastructural study of the rat ventral tegmental area (vol 17, pg 4037, 1997) SO JOURNAL OF NEUROSCIENCE LA English DT Correction, Addition DE dopamine; transporter; uptake; ultrastructure; ventral tegmental area; midbrain; mesocorticolimbic; electron microscopy; immunogold; dendritic release; plasma membrane; cocaine; amphetamine; neurotoxicity ID VESICULAR MONOAMINE TRANSPORTER-2; DENDRO-DENDRITIC SYNAPSES; SUBSTANTIA-NIGRA; TYROSINE-HYDROXYLASE; AUTORADIOGRAPHIC LOCALIZATION; ENDOPLASMIC-RETICULUM; REGIONAL DIFFERENCES; NUCLEUS-ACCUMBENS; INVIVO DIALYSIS; UPTAKE SITES AB The dopamine transporter (DAT) plays an important role in the plasmalemmal reuptake of dopamine and, thus, in the termination of normal dopaminergic neurotransmission. DAT is also a major binding site for cocaine and other stimulants, the psychoactive effects of which are associated primarily with the inhibition of dopamine reuptake within mesocorticolimbic dopaminergic neurons. We used electron microscopy with an anti-peptide antiserum directed against the N-terminal domain of DAT to determine the subcellular localization of this transporter in the rat ventral tegmental area (VTA), the region that contains the cell bodies and dendrites of these dopaminergic neurons. We show that in the VTA, almost 95% of the DAT immunogold-labeled profiles are neuronal perikarya and dendrites, and the remainder are unmyelinated axons. Within perikarya and large proximal dendrites, almost all of the DAT immunogold particles are associated with intracellular membranes, including saccules of Golgi and cytoplasmic tubulovesicles. In contrast, within medium-to small-diameter dendrites and unmyelinated axons, most of the DAT gold particles are located on plasma membranes. In dually labeled tissue, peroxidase reaction product for the catecholamine-synthesizing enzyme tyrosine hydroxylase is present in DAT-immunoreactive profiles. These findings suggest that intermediate and distal dendrites are both the primary sites of dopamine reuptake and the principal targets of cocaine and related psychostimulants within dopaminergic neurons in the VTA. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,BRANCH MOL NEUROBIOL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. EMORY UNIV,YERKES REG PRIMATE RES CTR,DIV NEUROSCI,ATLANTA,GA 30322. RP Nirenberg, MJ (reprint author), CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,411 E 69TH ST,ROOM KB-410,NEW YORK,NY 10021, USA. FU NIDA NIH HHS [DA04600]; NIMH NIH HHS [MH00078, MH40342] NR 69 TC 64 Z9 65 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1997 VL 17 IS 14 BP 5255 EP & PG 9 WC Neurosciences SC Neurosciences & Neurology GA XV075 UT WOS:A1997XV07500002 PM 9204909 ER PT J AU Glass, M Felder, CC AF Glass, M Felder, CC TI Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: Evidence for a G(s) linkage to the CB1 receptor SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cannabinoid; G-protein; adenylate cyclase; CB1 receptor; dopamine; D2 receptor; striatum ID SIGNAL-TRANSDUCTION PATHWAYS; CYCLIC-AMP ACCUMULATION; ADENYLATE-CYCLASE; BASAL GANGLIA; BETA-2-ADRENERGIC RECEPTOR; MOLECULAR-CLONING; PHOSPHOLIPASE-C; CALCIUM INFLUX; CHOLERA TOXIN; RAT STRIATUM AB Cannabinoids act at the CB1 receptor to inhibit adenylate cyclase activity via a pertussis toxin-sensitive G-protein. Within the striatum, CB1 receptors have been shown to be localized on the same neurons as G(i)-coupled dopamine D2 receptors. In this study we have examined the interactions of CB1 and D2 receptors on adenylate cyclase. In striatal neurons in primary culture, both the CB1 receptor agonist [3-(1,1 -dimethylheptyl)-11 -hydroxy-Delta(8)tetrahydrocannabinol] (HU210) and the D2 receptor agonist quinpirole inhibited forskolin-stimulated cAMP accumulation when applied separately. In contrast, HU210 and quinpirole in combination augmented cAMP accumulation. This augmentation was blocked by the CB1 receptor antagonist SR141716A or the D2 antagonist sulpride. Pertussis toxin treatment of striatal neurons prevented the inhibition of cAMP accumulation by D2 receptors but unmasked a cannabinoid receptor-mediated stimulatory effect on cAMP accumulation. The cannabinoid receptor-stimulated accumulation of cAMP was blocked in a concentration-dependent manner by SR141716A, suggesting that the response was regulated through the CB1 receptor. Similar augmentation of cAMP accumulation after pertussis toxin treatment was observed in Chinese hamster ovary (CHO) cells transfected with, and stably expressing, the CB1 receptor. This stimulation of cAMP was not Ca2+-sensitive and was unaffected by a range of protein kinase inhibitors. Treatment of the pertussis toxin-treated cells with cholera toxin before CB1 receptor activation amplified the stimulatory pathway, suggesting that this response was mediated through a G(s)-type G-protein. Stimulation of cAMP accumulation was not observed after pertussis toxin treatment of CHO cells expressing the human CB2 receptor, suggesting that this novel signaling pathway is unique to the cannabinoid CB1 receptor. C1 NIMH,LAB CELLULAR & MOL REGULAT,BETHESDA,MD 20892. OI Glass, Michelle/0000-0002-5997-6898 NR 43 TC 357 Z9 374 U1 1 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1997 VL 17 IS 14 BP 5327 EP 5333 PG 7 WC Neurosciences SC Neurosciences & Neurology GA XV075 UT WOS:A1997XV07500010 PM 9204917 ER EF