FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Tkaczyk, C Tuan, A Kirshenbaum, A Metcalfe, DD Gilfillan, AM AF Tkaczyk, C Tuan, A Kirshenbaum, A Metcalfe, DD Gilfillan, AM TI FceRI-Aggregation initiates both tyrosine phosphorylation and tyrosine dephosphorylation in human mast cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 262 BP S87 EP S87 DI 10.1016/S0091-6749(00)90692-4 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100260 ER PT J AU Trostel, A Druey, K AF Trostel, A Druey, K TI D-AKAP2 inhibits Gs alpha-induced cAMP generation in HEK293 cells SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 1062 BP S360 EP S361 DI 10.1016/S0091-6749(00)91488-X PN 2 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530101056 ER PT J AU Uzel, G Donnan, S Brown, M Akin, C Cook, J Holland, S AF Uzel, G Donnan, S Brown, M Akin, C Cook, J Holland, S TI Multiple immunophenotypic abnormalities in patients with pulmonary nontuberculous mycobacterial infections SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Natl Jewish Med & Res Ctr, New Hyde Park, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 534 BP S176 EP S177 DI 10.1016/S0091-6749(00)90962-X PN 2 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100530 ER PT J AU Wood, P Lammas, D Casanova, JL Holland, S Kumararatne, D AF Wood, P Lammas, D Casanova, JL Holland, S Kumararatne, D TI Lack of TH1 cytokines and atopic disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Birmingham, Dept Immunol, Birmingham, W Midlands, England. Hop Necker Enfants Malad, Unite Immunol, Paris, France. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2000 VL 105 IS 1 SU S MA 325 BP S109 EP S109 DI 10.1016/S0091-6749(00)90754-1 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 287WR UT WOS:000085530100322 ER PT J AU Zinaman, MJ Brown, CC Selevan, SG Clegg, ED AF Zinaman, MJ Brown, CC Selevan, SG Clegg, ED TI Semen quality and human fertility: A prospective study with healthy couples SO JOURNAL OF ANDROLOGY LA English DT Article DE male fertility; sperm parameters ID INFERTILITY; MOTILITY AB Measures of semen quality are used as surrogate measures of male fertility in clinical andrology, reproductive toxicology, epidemiology, and risk assessment, However, only limited data are available to relate those measures to fertility. This prospective study with 210 reproductive-age couples was conducted to provide information on the value of semen quality measures for predicting human male fertility potential and for development of models to estimate the effects of changes in semen quality on fertility in a given population for risk assessment. Couples without known risk factors for infertility and who had discontinued contraception to have a child were accepted. The study followed each couple for up to 12 menstrual cycles while they attempted to conceive and evaluated semen quality measures from multiple ejaculates per man with known abstinence intervals. For each cycle, the day of ovulation was predicted, and the couple was advised to have intercourse multiple times on that day and on the days around it. Among the demographic variables assessed, parity, contraception status prior to entering the study, male education level, and male smoking were associated significantly with 12-cycle pregnancy rate. Several semen quality measures also were associated significantly with pregnancy rate, with percentage morphologically normal sperm by strict criteria and measures involving total number of sperm showing particularly strong associations. Localized regression-smoothing plots of semen quality data against proportion of couples pregnant suggested levels below which fertility declines for several semen quality measures. These results have applications in both clinical andrology and in assessment of risk to male fecundity from environmental or pharmaceutical exposures. In particular, they contribute information on behavior of fertility with varying semen quality and can allow development of models to predict effects on fertility in populations from decrements in semen quality. C1 Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. RP Zinaman, MJ (reprint author), Loyola Univ, Med Ctr, Dept Obstet & Gynecol, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 22 TC 112 Z9 123 U1 0 U2 8 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD JAN-FEB PY 2000 VL 21 IS 1 BP 145 EP 153 PG 9 WC Andrology SC Endocrinology & Metabolism GA 279FN UT WOS:000085033900015 PM 10670528 ER PT J AU Gerber, L El-Gabalawy, H Arayssi, T Furst, G Yarboro, C Schumacher, HR AF Gerber, L El-Gabalawy, H Arayssi, T Furst, G Yarboro, C Schumacher, HR TI Polyarticular arthritis, independent of rheumatoid factor, is associated with poor functional outcome in recent onset inflammatory synovitis SO JOURNAL OF BACK AND MUSCULOSKELETAL REHABILITATION LA English DT Article DE inflammatory arthritis; functional activity ID HEALTH-STATUS; IMPACT; DISABILITY; DISEASE AB The biological, physical and functional status change was measured in 104 patients with recent (< 1 year) onset synovitis. Measurements were taken initially and at 1 year. The purpose was to determine which biological and physical measures correlated with pour performance. Patients completed questionnaires quantifying activity, (the Human Activity Profile [HAP] and Sickness Impact Profile [SIP]), pain (Wisconsin Brief Pain Inventory), fatigue (Multidimensional Assessment of Fatigue). sleep, and mood (POMS and CESD). They were evaluated for articular involvement (Ritchie: Index) and biological markers of disease activity (platelets, sedimentation rate, C-reactive protein and rheumatoid factor) (RF). In all, 30 men and 74 women participated. A total of 45 patients met the American College of Rheumatology criteria for rheumatoid arthritis (RA): of these, 24 were rheumatoid factor (RF) positive, 18 had spondylitis, and 41 had unclassified arthritis. Low activity level at 1 year (HAP and SIP) correlated with high numbers of inflamed joints initially (p < 0.002); with more than 10 involved joints regardless of diagnostic group (p = 0.001); and joint symmetry (p < 0.009) A high platelet count was associated with low activity level at 1 year (p = 0.01): and high sedimentation rate was associated with mon pain (p < 0.05). Low activity level (p < 0.04), fatigue (p = 0.03) and sleeplessness (p = 0.02) were correlated with RF+ RA. C1 NIH, Dept Rehabil Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Gerber, L (reprint author), NIH, Dept Rehabil Med, Warren Grant Magnuson Clin Ctr, Bldg 10,RM 6S235,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA. OI Arayssi, Thurayya/0000-0003-2469-0272 NR 19 TC 6 Z9 6 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8127 J9 J BACK MUSCULOSKELET JI J. Back Musculoskelet. Rehabil. PY 2000 VL 14 IS 3 BP 105 EP 109 PG 5 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 455FF UT WOS:000170016300005 ER PT J AU Hill, SA AF Hill, SA TI Opa expression correlates with elevated transformation rates in Neisseria gonorrhoeae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PILIN ANTIGENIC VARIATION; MEMBRANE PROTEIN-II; GENETIC TRANSFORMATION; DNA TRANSFORMATION; OPACITY PROTEINS; GONOCOCCI; COMPETENCE; SEQUENCE; INFECTION; MUTANTS AB Neisseria gonorrhoeae is naturally competent for DNA transformation. Under most conditions encountered in vivo, gonococci express one or more opacity (Opa) proteins on their surfaces. Recently, it was shown that DNA preferentially binds to the surfaces of Opa-expressing organisms compared to those of isogenic Opa-negative strains, presumably due to the numerous cationic residues in the predicted surface-exposed loops of the Opa protein. This study examined whether Opa-DNA interactions actually influence DNA transformation of the gonococcus. The data show that Opa-expressing gonococci are more efficient recipients of DNA for transformation and are more susceptible to exogenous DNase I treatment at early stages during the DNA transformation process than non-Opa expressors, Furthermore, inhibition of the transformation process was demonstrable for Opa(+) populations when either nonspecific DNA or the polyanion heparin was used. Overall, the data suggest that Opa expression, with its presumptive positive surface charge contribution, promotes DNA transformation by causing a more prolonged sequestration of donor DNA at the cell surface, which translates into more efficient transformation over time. C1 No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA. NIH, Microbial Struct & Funct Lab, Rocky Mt Labs, NIAID, Hamilton, MT 59840 USA. RP Hill, SA (reprint author), No Illinois Univ, Dept Biol Sci, De Kalb, IL 60115 USA. NR 38 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2000 VL 182 IS 1 BP 171 EP 178 PG 8 WC Microbiology SC Microbiology GA 265WP UT WOS:000084269400023 PM 10613877 ER PT J AU King, RA Madsen, PL Weisberg, RA AF King, RA Madsen, PL Weisberg, RA TI Constitutive expression of a transcription termination factor by a repressed prophage: Promoters for transcribing the phage HK022 nun gene SO JOURNAL OF BACTERIOLOGY LA English DT Article ID N-ANTITERMINATION PROTEIN; BACTERIOPHAGE-LAMBDA; RNA-POLYMERASE; DNA-BINDING; SINGLE; PHAGE-HK022; SUPPRESSOR; MUTATIONS; CLONING; REGION AB Lysogens of phage HK022 are resistant to infection by phage lambda. Lambda resistance is caused by the action of the HK022 Nun protein, which prematurely terminates early lambda transcripts. We report here that transcription of the nun gene initiates at a constitutive prophage promoter, P-Nun, located just upstream of the protein coding sequence. The 5 ' end of the transcript was determined by primer extension analysis of RNA isolated from HK022 lysogens or RNA made in vitro by transcribing a template containing the promoter with purified Escherichia call RNA polymerase. Inactivation of P-Nun by mutation greatly reduced Nun activity and Nun antigen in an HK022 lysogen, However, a low level of residual activity was detected, suggesting that a secondary promoter also contributes to nun expression. We found one possible secondary promoter, P-Nun', just upstream of P-Nun. Neither promoter is likely to increase the expression of other phage genes in a lysogen because their transcripts should be terminated downstream of nun. We estimate that HK022 lysogens in stationary phase contain several hundred molecules of Nun per cell and that cells in exponential phase probably contain fewer. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP King, RA (reprint author), NICHHD, Mol Genet Lab, NIH, Bldg 6B,Room 408,6 Ctr Dr,MSC 2785, Bethesda, MD 20892 USA. NR 37 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2000 VL 182 IS 2 BP 456 EP 462 DI 10.1128/JB.182.2.456-462.2000 PG 7 WC Microbiology SC Microbiology GA 270BH UT WOS:000084515200026 PM 10629193 ER PT J AU Jernigan, RL Bahar, I Covell, DG Atilgan, AR Erman, B Flatow, DT AF Jernigan, RL Bahar, I Covell, DG Atilgan, AR Erman, B Flatow, DT TI Relating the structure of HIV-1 reverse transcriptase to its processing step SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article; Proceedings Paper CT 11th Conversation in Biomolecular Stereodynamics CY JUN 15-19, 1999 CL SUNY ALBANY, ALBANY, NY SP SUNY Albany, Dept Chem, SUNY Albany, Inst Biomolec Stereodynam HO SUNY ALBANY ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIBRATIONAL DYNAMICS; ANGSTROM RESOLUTION; SINGLE-PARAMETER; FOLDED PROTEINS; FLUCTUATIONS; MOTIONS; DNA; COMPLEX; FORMS AB By treating an enzyme as a coarse-grained uniform block of material, utilizing only the alpha -Carbon positions, the normal modes of motion can be obtained. For reverse transcriptase the slower of these motions are suggestive of being involved in the processing step, where the RNA or DNA strand is copied onto a new DNA strand at a polymerase site, and the RNA strand is subsequently cut up at the distant Ribonuclease H site. The slowest mode of motion involves hinge bending about a site midway between the polymerase and Ribonuclease H sites, suggesting that it can push or pull the RNA strand between these two sites. Pulling the nucleic acid strand would require tight binding to the RNase H site. The next slowest mode involves a hinge that opens and closes the protein like a clamp, which could facilitate the release of the nucleic acids for their step-wise progression. The third mode could rotate the substrate. An overall description of the step-wise processing step would involve close coordination among these steps. Results suggest that the smaller p51 subunit serves only as ballast to support the various modes of motion involving the different parts of the p66 subunit. C1 NCI, Mol Struct Sect, Lab Expt & Computat Biol, Div Basic Sci,NIH, Bethesda, MD 20892 USA. Bogazici Univ, Ctr Polymer Res, TR-80815 Bebek, Turkey. TUBITAK Adv Polymer Mat ResCtr, TR-80815 Bebek, Turkey. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Sabanci Univ, Sabanci Ctr, TR-80745 Istanbul, Turkey. RP Jernigan, RL (reprint author), NCI, Mol Struct Sect, Lab Expt & Computat Biol, Div Basic Sci,NIH, MSC 5677, Bethesda, MD 20892 USA. EM Robert_Jernigan@nih.gov RI Atilgan, Ali Rana/A-7805-2011; Jernigan, Robert/A-5421-2012; OI ERMAN, BURAK/0000-0002-2496-6059 NR 23 TC 2 Z9 2 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PY 2000 SI S1 BP 49 EP 55 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 375PH UT WOS:000165410100007 ER PT J AU Kumar, S Tsai, CJ Ma, BY Nussinov, R AF Kumar, S Tsai, CJ Ma, BY Nussinov, R TI Contribution of salt bridges toward protein thermostability SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article; Proceedings Paper CT 11th Conversation in Biomolecular Stereodynamics CY JUN 15-19, 1999 CL SUNY ALBANY, ALBANY, NEW YORK SP SUNY Albany, Dept Chem, SUNY Albany, Inst Biomolec Stereodynam HO SUNY ALBANY ID HYDROPHOBIC FOLDING UNITS; COMPLETE GENOME SEQUENCE; ION-PAIR NETWORKS; GLUTAMATE-DEHYDROGENASE; PYROCOCCUS-FURIOSUS; THERMAL-STABILITY; ACTIVE-SITE; HYPERTHERMOPHILIC ARCHAEBACTERIUM; ELECTROSTATIC INTERACTIONS; HIGH-TEMPERATURES AB We present an extensive study of the structural factors suggested to be responsible for thermostability, in 18 nonredundant families of thermophilic and mesophilic proteins. Each of these 18 families consists of homologous thermophile-mesophile pairs. with high resolution crystal structures for both pair-members available in the Protein Data Bank (PDB). We observe that both the thermophilic and the mesophilic proteins have similar hydrophobicities, oligomeric states, and hydrogen bonds. On the other hand, salt bridges increase in most of the thermophilic proteins. Yet, on the other hand, salt bridges have been proposed to destabilize protein structures. Hence, here we seek to understand why do salt bridges occur more frequently in thermophilic proteins. Investigating this problem, we focus on the glutamate dehydrogenase family. Computation of the electrostatic contribution of salt bridge energies by solving the Poisson equation in a continuum solvent medium, shows that the salt bridges in the glutamate dehydrogenase from the hyperthermophile Pyrococcus furiosus are highly stabilizing. In contrast. the salt bridges in the mesophilic Clostridium symbiosum glutamate dehydrogenase contribute only marginally to protein stability. The presence of a larger number of salt bridges cooperatively enhances their strength. Our results indicate that salt bridges and their networks may have an important role in rigidifying the protein structure at high temperatures. Formation of salt bridge networks may help in explaining the increased occurrence and stability of salt bridges in hyperthermophiles. C1 NCI, Intramural Res Support Program, SAIC Frederick, Canc Res & Dev Ctr,lab Expt & Computat Biol, Frederick, MD 21702 USA. NCI, Lab Expt & Computat Biol, FCRDC, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Canc Res & Dev Ctr,lab Expt & Computat Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. OI Ma, Buyong/0000-0002-7383-719X NR 52 TC 16 Z9 16 U1 0 U2 5 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PY 2000 SI S1 BP 79 EP 85 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 375PH UT WOS:000165410100011 ER PT J AU Karamychev, VN Panyutin, IG Neumann, RD Zhurkin, VB AF Karamychev, VN Panyutin, IG Neumann, RD Zhurkin, VB TI DNA and RNA folds in transcription complex as evidenced by iodine-125 radioprobing SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article; Proceedings Paper CT 11th Conversation in Biomolecular Stereodynamics CY JUN 15-19, 1999 CL SUNY ALBANY, ALBANY, NEW YORK SP SUNY Albany, Dept Chem, SUNY Albany, Inst Biomolec Stereodynam HO SUNY ALBANY ID ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; POLYMERASE-II; ANGSTROM RESOLUTION; TEMPLATE STRAND; ELONGATION; INITIATION; HYBRID; BACTERIOPHAGE-T7; TERMINATION AB Folding of the DNA and RNA strands in an arrested T7 RNA polymerase (RNAP) transcription complex was studied by radioprobing, a novel method based on an analysis of the strand breaks produced by decay of the iodine-125 incorporated at the C5 position of cytosine. I-125- labeled cytosines were incorporated into transcripts at different positions relative to the site of the arrest. The intensities of the DNA breaks inversely correlate with the distances from the I-125 decay site, so the radioprobing data provide information about the spatial RNA/DNA folding during transcription. We found that the yield of DNA strand breaks is significantly higher in the template than the non-template strand. This is consistent with local opening of the DNA duplex and formation of a hybrid between RNA and the template DNA strand. Our data demonstrate that the RNA-DNA hybrid has a nonuniform A-like structure. When the I-125 is incorporated seven nucleotides from the active center of RNAP, the yield of strand breaks is substantially lower than if I-125 is positioned at the ends of the hybrid. Consequently, the DNA and RNA strands are located closer to each other at the ends of the hybrid and somehow separated in the middle. Surprisingly, the I-125-induced breaks were detected in both DNA strands upstream from the transcription "bubble" indicating that DNA and RNA are closely associated outside the RNAP cleft. Thus, radioprobing data imply that the RNA/DNA fold in the complex with T7 RNAP is more complicated than had been anticipated by the existing models. Based on the present data, we suggest a sterically feasible model explaining how formation of the long RNA-DNA hybrid can result in the initiation-to-elongation switch in the T7 transcription complex. According to this model, the topological linkage between the DNA and RNA strands provides the necessary stability for the elongation complex, while permitting movement of the polymerase along the DNA duplex. C1 Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Novosibirsk Bioorgan Chem Inst, Novosibirsk 630090, Russia. RP Panyutin, IG (reprint author), Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NR 42 TC 2 Z9 2 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PY 2000 SI S1 BP 155 EP 167 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 375PH UT WOS:000165410100021 ER PT J AU Kamath, S Sarma, MH Zhurkin, VB Turner, CJ Sarma, RH AF Kamath, S Sarma, MH Zhurkin, VB Turner, CJ Sarma, RH TI DNA bending and sugar switching SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article; Proceedings Paper CT 11th Conversation in Biomolecular Stereodynamics CY JUN 15-19, 1999 CL SUNY ALBANY, ALBANY, NY SP SUNY Albany, Dept Chem, SUNY Albany, Inst Biomolec Stereodynam HO SUNY ALBANY ID CRYSTAL-STRUCTURE; CONFORMATIONAL-ANALYSIS; COUPLING-CONSTANTS; BENT DNA; NMR; COMPLEX; TRACT; RING; POLY(DA).POLY(DT); NUCLEOTIDES AB Using high frequency antiphase NMR spectroscopy and computer simulations of the antiphase spectra, we studied the equlibria in the sugar conformations in the DNA duplex 11-mer containing the AAA tract surrounded by cytosines. We demonstrate that at the 3'-end of the A-tract, the sugar switches from the common S-conformer (B-like form) to the N-conformer (A-like form) with the probability of 50-60%, thus creating a purine-pyrimidine step with heteronomous characteristics. The presence of this local B-Ajunction in one strand leads to compression of the interphosphate distance in this strand. We calculate the effect of this sugar switch on the helical parameters that are related to DNA bending. Finally, we suggest that the heteronomous deformation present in the A(n)C motif of unbound DNA duplexes might be the initial recognition site for proteins which bind to such junctions; and that in A(n)C stretches, DNA bending is a complicated dynamic process, ie., locally noncanonical N conformers of the sugar phosphate backbone mix in with the B-like S conformers leading to bending. C1 SUNY Albany, Dept Chem, Inst Biomol Stereodynam, Albany, NY 12222 USA. NCI, Mol Struct Sect, Lab Computat & Expt Biol, NIH, Bethesda, MD 20892 USA. MIT, Francis Bitter Natl Magnet Lab, Cambridge, MA 02139 USA. RP SUNY Albany, Dept Chem, Inst Biomol Stereodynam, 1400 Washington Ave, Albany, NY 12222 USA. EM rhs07@cnsvax.albany.edu NR 40 TC 0 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0739-1102 EI 1538-0254 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PY 2000 SI S2 BP 317 EP 325 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 375PJ UT WOS:000165410200019 ER PT J AU Grzesik, WJ Cheng, H Oh, JS Kuznetsov, SA Mankani, MH Uzawa, K Robey, PG Yamauchi, M AF Grzesik, WJ Cheng, H Oh, JS Kuznetsov, SA Mankani, MH Uzawa, K Robey, PG Yamauchi, M TI Cementum-forming cells are phenotypically distinct from bone-forming cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE cementum; bone; cementoblasts; osteoblasts; cementogenesis ID MARROW STROMAL FIBROBLASTS; RAT MOLARS; IN-VITRO; CELLULAR CEMENTOGENESIS; FIBER ARRANGEMENT; MATRIX PROTEINS; EXPRESSION; VIVO; IMMUNOLOCALIZATION; SIALOPROTEIN AB Normal human cementum-derived cells (HCDCs), expanded in vitro, Formed mineralized matrix when attached to a ceramic carrier and transplanted subcutaneously into immunodeficient mice, The mineralized matrix elaborated by transplanted HCDC exhibited several features identical to cementum in situ and was significantly different from bone deposited by similarly transplanted human bone marrow stromal cells (BMSCs), No bone marrow formation and very few or no tartrate-resistant acid phosphatase (TRAP)-positive cells (osteoclasts and osteoclastic precursors) were found in HCDC transplants, In contrast, in BMSC transplants both hematopoiesis and TRAP-positive cells were routinely observed. Furthermore, compared with BMSC-derived matrix, HCDC-derived matrix nas less cellular, numerous empty lacunae were present, and fewer cells were found on the cementum matrix/ceramic carrier interface, The organization of collagen fibers in HCDC-derived matrix, as visualized by using the Picrosirus red staining method, was similar to cementum, with typical unorganized bundles of collagen fibers, In contrast, bone matrix elaborated by transplanted BMSC had lamellar structure, identical to mature bone in situ, Finally, cementocytes embedded in the cementum-like matrix were immunopositive for fibromodulin and lumican, whereas osteocytes within the bonelike matrix were negative. This pattern is consistent with the cementum and bone in situ, respectively. These results indicate that human cementum cells are phenotypically distinct from bone cells and provide further validation of the combined in vitro/in vivo model of human cementogenesis recently developed in our laboratory. C1 Univ N Carolina, Dent Res Ctr, Dept Periodont, Sch Dent, Chapel Hill, NC 27599 USA. Chapel Hill High Sch, Chapel Hill, NC USA. NIH, Craniofacial & Skeletal Dis Branch, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Grzesik, WJ (reprint author), Univ N Carolina, Dent Res Ctr, Dept Periodont, Sch Dent, CB 7455,307 Dental Res Bldg, Chapel Hill, NC 27599 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU NIDCR NIH HHS [DE 10489, DE-12403] NR 35 TC 35 Z9 35 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2000 VL 15 IS 1 BP 52 EP 59 DI 10.1359/jbmr.2000.15.1.52 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 268MU UT WOS:000084420800009 PM 10646114 ER PT J AU Bianco, P Riminucci, M Majolagbe, A Kuznetsov, SA Collins, MT Mankani, MH Corsi, A Bone, HG Wientroub, S Spiegel, AM Fisher, LW Robey, PG AF Bianco, P Riminucci, M Majolagbe, A Kuznetsov, SA Collins, MT Mankani, MH Corsi, A Bone, HG Wientroub, S Spiegel, AM Fisher, LW Robey, PG TI Mutations of the GNAS1 gene, stromal cell dysfunction, and osteomalacic changes in non-McCune-Albright fibrous dysplasia of bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fibrous dysplasia; McCune-Albright syndrome; mutation analysis; Gs alpha; GNAS1; PNA; transplantation; animal model ID ACTIVATING G(S)ALPHA MUTATION; PROTEIN-COUPLED RECEPTORS; STIMULATORY G-PROTEIN; INTRAVENOUS PAMIDRONATE; SIGNAL-TRANSDUCTION; MOLECULAR-BASIS; ALPHA-SUBUNIT; IN-VIVO; DEFECTS; DISEASE AB Activating missense mutations of the GNAS1 gene, encoding the alpha subunit of the stimulatory G protein (Gs), have been identified in patients with the McCune-Albright syndrome (MAS; characterized by polyostotic fibrous dysplasia, cafe au lait skin pigmentation, and endocrine disorders). Because fibrous dysplasia (FD) of bone also commonly occurs outside of the context of typical MAS, we asked whether the same mutations could be identified routinely in non-MAS FD lesions, We analyzed a series of 8 randomly obtained, consecutive cases of non-MAS FD and identified R201 mutations in the GNAS1 gene in all of them by sequencing cDNA generated by amplification of genomic DNA using a standard primer set and by using a novel, highly sensitive method that uses a protein nucleic acid (PNA) primer to block amplification of the normal allele. Histologic findings were not distinguishable from those observed in MAS-related FD and included subtle changes in cell shape and collagen texture putatively ascribed to excess endogenous cyclic adenosine monophosphate (cAMP), Osteomalacic changes (unmineralized osteoid) were prominent in lesional FD bone. In an in vivo transplantation assay, stromal cells isolated from FD failed to recapitulate a normal ossicle; instead, they generated a miniature replica of fibrous dysplasia, These data provide evidence that occurrence of GNAS1 mutations, previously noted in individual cases of FD, is a common and perhaps constant finding in non-MAS FD. These findings support the view that FD, MAS, and nonskeletal isolated endocrine lesions associated with GNAS1 mutations represent a spectrum of phenotypic expressions (likely reflecting different patterns of somatic mosaicism) of the same basic disorder, We conclude that mechanisms underlying the development of the FD lesions, and hopefully mechanism-targeted therapeutic approaches to be developed, must also be the same in MAS and non-MAS FD. C1 NIH, Craniofacial & Skeletal Dis Branch, Nat Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. St Johns Med Ctr, Michigan Bone & Min Clin, Detroit, MI USA. Tel Aviv Univ, Ctr Med, Dept Pediat Orthoped, Dana Childrens Hosp,Sackler Sch Med, IL-69978 Tel Aviv, Israel. NIH, Metab Dis Branch, NIDDK, Bethesda, MD 20892 USA. Univ Aquila, Dipartimento Med Sperimentale, I-67100 Laquila, Italy. RP Robey, PG (reprint author), NIH, Craniofacial & Skeletal Dis Branch, Nat Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.1029] NR 34 TC 127 Z9 132 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2000 VL 15 IS 1 BP 120 EP 128 DI 10.1359/jbmr.2000.15.1.120 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 268MU UT WOS:000084420800016 PM 10646121 ER PT J AU Medgyes, A Bajza I Farkas, E Pozsgay V Liptak, A AF Medgyes, A Bajza, I Farkas, E Pozsgay, V Liptak, A TI Synthetic studies towards the O-specific polysaccharide of Shigella sonnei SO JOURNAL OF CARBOHYDRATE CHEMISTRY LA English DT Article ID PROMOTED REACTIONS; THIOGLYCOSIDES; DERIVATIVES; OXIDATION; ACCEPTOR AB Synthetic routes are described to zwitter-ionic disaccharides that are diastereoisomerically related to frame-shifted repeating units of the title polysaccharide that contains 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose and 2-acetamido-2-deoxy-L-altruronic acid. The intermediates corresponding to the trideoxygalactose residue feature acylamino functions at C-2 and an azido group at C-4. Best results were obtained with N-phthaloyl- and N-trichloroacetyl-protected derivatives. The intermediates corresponding to the uronic acid residue were either a D-altruronic acid-derived acceptor or a D-altrose-derived donor in which C-6 was oxidized after disaccharide formation. C1 Univ Debrecen, Inst Biochem, Debrecen, Hungary. Hungarian Acad Sci, Res Grp Carbohydrates, H-1051 Budapest, Hungary. NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. RP Liptak, A (reprint author), Univ Debrecen, Inst Biochem, Debrecen, Hungary. NR 21 TC 3 Z9 3 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0732-8303 J9 J CARBOHYD CHEM JI J. Carbohydr. Chem. PY 2000 VL 19 IS 3 BP 285 EP 310 DI 10.1080/07328300008544079 PG 26 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 305MJ UT WOS:000086543600002 ER PT J AU Kikyo, N Wolffe, AP AF Kikyo, N Wolffe, AP TI Reprogramming nuclei: insights from cloning, nuclear transfer and heterokaryons SO JOURNAL OF CELL SCIENCE LA English DT Editorial Material DE cloning; nucleus; cell cycle; chromatin; histone; transcriptional control ID EARLY XENOPUS-EMBRYOS; MAJOR DEVELOPMENTAL TRANSITION; TRANSCRIPTION IN-VIVO; BINDING-PROTEIN MECP2; FULL-TERM DEVELOPMENT; LINKER HISTONES B4; CELL-CYCLE-STAGE; DNA-REPLICATION; ERYTHROCYTE NUCLEI; GENE-EXPRESSION AB Mammals and amphibians can be cloned following the transfer of embryonic nuclei into enucleated eggs or oocytes. As nuclear functions become more specialized in the differentiated cells of an adult, successful cloning using these nuclei as donors becomes more difficult. Differentiation involves the assembly of specialized forms of repressive chromatin including linker histones, Polycomb group proteins and methyl-CpG-binding proteins. These structures compartmentalize chromatin into functional domains and maintain the stability of the differentiated state through successive cell divisions. Efficient cloning requires the erasure of these structures. The erasure can be accomplished through use of molecular chaperones and enzymatic activities present in the oocyte, egg or zygote. We discuss the mechanisms involved in reprogramming nuclei after nuclear transfer and compare them with those that occur during remodeling of somatic nuclei after heterokaryon formation. Finally we discuss how one might alter the properties of adult nuclei to improve the efficiency of cloning. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. NR 156 TC 94 Z9 107 U1 1 U2 8 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN PY 2000 VL 113 IS 1 BP 11 EP 20 PG 10 WC Cell Biology SC Cell Biology GA 279GK UT WOS:000085035900004 PM 10591621 ER PT J AU Bernier, M Kole, HK Montrose-Rafizadeh, C Kole, S AF Bernier, M Kole, HK Montrose-Rafizadeh, C Kole, S TI Discrete region of the insulin receptor carboxyl terminus plays key role in insulin action SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE receptor tyrosine kinase; signal transduction; thymidine incorporation; phosphatidylinositol 3 '-kinase; mitogen-activated protein kinase; CHO cells; transfection ID FACTOR-I RECEPTORS; PROTEIN-TYROSINE-PHOSPHATASE; KINASE-ACTIVITY; SIGNAL-TRANSDUCTION; BETA-SUBUNIT; COOH-TERMINUS; INTACT-CELLS; C-TERMINUS; DOMAIN; PHOSPHORYLATION AB In the present study, we attempted to determine the importance of a 23-amino-acid sequence within the carboxyl terminus of the human insulin receptor (IR) molecule in modulating insulin action in Chinese hamster ovary cells. Stable expression of a minigene encoding the receptor fragment led to an increase in insulin-induced IR autophosphorylation that was 2.4-fold higher when compared to that of IR-expressing cells transfected with empty vector. Insulin-stimulated downstream signaling was also significantly elevated in cells expressing the minigene. It was found that expression of the minigene had no effect toward insulin-like growth factor I receptor kinase activity and function. These results indicate that the IR carboxyl terminus contains a motif that acts as a physiologic modulator of insulin signaling. Published 2000 Wiley-Liss, Inc.(dagger). C1 NIA, Diabet Sect, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Bernier, M (reprint author), NIA, Diabet Sect, Clin Invest Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Bernier, Michel/0000-0002-5948-368X NR 34 TC 0 Z9 1 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2000 VL 78 IS 1 BP 160 EP 169 DI 10.1002/(SICI)1097-4644(20000701)78:1<160::AID-JCB15>3.0.CO;2-G PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 317FV UT WOS:000087216100015 PM 10797575 ER PT J AU Reyes-Cruz, G Vazquez-Prado, J Muller-Esterl, W Vaca, L AF Reyes-Cruz, G Vazquez-Prado, J Muller-Esterl, W Vaca, L TI Regulation of the human bradykinin B2 receptor expressed in sf21 insect cells: A possible role for tyrosine kinases SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE human bradykinin receptor; receptor desensitization; intracellular calcium; Sf21 cells ID PROTEIN-COUPLED RECEPTORS; SUBSTANCE-P RECEPTOR; SF9 CELLS; SIGNAL-TRANSDUCTION; MUSCARINIC RECEPTOR; INDUCED PHOSPHORYLATION; FUNCTIONAL EXPRESSION; MUSCLE-CELLS; C-DELTA; DESENSITIZATION AB The functional regulation of the human bradykinin B2 receptor expressed in sf21 cells was studied. Human bradykinin B2 receptors were immunodetected as a band of 75-80 kDa in membranes from recombinant baculovirus-infected cells and visualized at the plasma membrane, by confocal microscopy, using an antibody against an epitope from its second extracellular loop. B2 receptors, detected in membranes by [H-3-bradykinin] binding, showed a Kd of 0.66 nmol/L and an expression level of 2.57 pmol/mg of protein at 54 h postinfection. In these cells, bradykinin induced a transient increase of intracellular calcium ([Ca2+](i)) in fura 2-AM loaded sf21 cells, and promoted [S-35]-GTP(gamma)S binding to membranes. The effects of bradykinin were dose dependent (with an EC50 of 50 nmol/L for calcium mobilization) and were inhibited by N-alpha-adamantaneacetyl-D-Arg-[Hyp(3),Thi(5,8),D-phe(7)]-Bk, a specific B2 receptor antagonist. When the B2 antagonist was applied at the top of the calcium transient, it accelerated the decline of the peak, suggesting that calcium mobilization at this point was still influenced by receptor occupation. No calcium mobilization was elicited by 1 mu mol/L (Des-Arg(9))-Bk a B1 receptor agonist that did not inhibit the subsequent action of 100 nmol/L bradykinin. No effect of bradykinin was detected in uninfected cells or cells infected with the wild-type baculovirus. Bradykinin-induced [Ca2+](i) mobilization was increased by genistein and tyrphostin A51. These tyrosine kinase inhibitors did not modify basal levels of [Ca2+](i). Homologous desensitization of the B2 receptor was observed after repeated applications of bradykinin, which resulted in attenuated changes in intracellular calcium. In addition, genistein promoted an increased response to a third exposure to the agonist when applied after washing the cells that had been previously challenged with two increasing doses of bradykinin. Genistein did not affect the calcium mobilization induced by activation of the endogenous octopamine G protein-coupled receptor or by thapsigargin. The B2 receptor, detected by confocal microscopy in unpermeabilized cells, remained constant at the surface of cells stimulated with bradykinin for 10 min, in the presence or absence of genistein. Agonist-promoted phosphorylation of the B2 receptor was markedly accentuated by genistein treatment. Phosphoaminoacid analysis revealed the presence of phosphoserine and traces of phosphothreonine, but not phosphotyrosine, suggesting that the putative tyrosine kinase(s), activated by bradykinin, could act in a step previous to receptor phosphorylation. Interestingly, genistein prevented agonist-induced G protein uncoupling from B2 receptors, determined by in vitro bradykinin-stimulated [S-35]-GTP(gamma)S binding, in membranes from bradykinin pretreated cells. Our results suggest that tyrosine kinase(s) regulate the activity of the human B2 receptor in sf21 cells by affecting its coupling to G proteins and its phosphorylation. (C) 2000 Wiley-Liss, inc. C1 Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Mexico City 04510, DF, Mexico. Univ Mainz, Inst Physiol Chem & Pathobiochem, D-55099 Mainz, Germany. RP Reyes-Cruz, G (reprint author), NIDDK, Metab Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 8C101, Bethesda, MD 20892 USA. RI VAZQUEZ-PRADO, JOSE/C-1630-2017; OI Vaca, Luis/0000-0003-2266-4847 NR 59 TC 13 Z9 13 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2000 VL 76 IS 4 BP 658 EP 673 DI 10.1002/(SICI)1097-4644(20000315)76:4<658::AID-JCB14>3.0.CO;2-7 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 280KH UT WOS:000085101600014 PM 10653985 ER PT J AU Boone, CW Kelloff, GJ AF Boone, CW Kelloff, GJ TI Endpoint markers for cancer chemoprevention trials derived from the lesion of precancer (intraepithelial neoplasia) measured by computer-assisted quantitative image analysis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Translational Chemoprevention - Breast and Colon Cancer CY JUN 21-24, 1998 CL HAIFA, ISRAEL SP Chemoprevent Branch, Div Canc Prevent, Control Natl Canc Inst, Israel Canc Assoc, Univ Michigan DE endpoint markers; chemoprevention trials; computer-assisted image analysis AB Endpoint markers for cancer chemoprevention clinical trials are described that are developed from the morphological properties of the precancerous lesion of intraepithelial neoplasia itself, as measured by computer-assisted quantitative image analysis. The markers include increased proliferative fraction (percentage MIB-1 positive nuclear area); nuclear DNA content (DNA ploidy), including DNA content exceeding fivefold the haploid amount (5C-exceeding rate); nuclear/nucleolar morphometry; and disorganization of nuclear chromatin pattern as characterized by Markovian parameters and other functions. A significant new advance in image analysis is the process of "tiling," in which hundreds of fu II monitor image fields of a given histological section at X40 magnification are reduced in size and fused seamlessly to produce a single image of the histological section at X1.25 magnification. The operator may review the low-power image and retrieve x40 magnification of any desired area by point/clicking with a mouse, J. Cell. Biochem. Suppl. 34:67-72, 2000. Published 2000 Wiley-Liss, Inc.(dagger) C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Boone, CW (reprint author), 6130 Execut Blvd, Rockville, MD 20815 USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2000 SU 34 BP 67 EP 72 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 298YV UT WOS:000086169600012 ER PT J AU Lawrence, JA Malpas, PB Sigman, CC Kelloff, GJ AF Lawrence, JA Malpas, PB Sigman, CC Kelloff, GJ TI Clinical development of estrogen modulators for breast cancer chemoprevention in premenopausal vs. postmenopausal women SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Translational Chemoprevention - Breast and Colon Cancer CY JUN 21-24, 1998 CL HAIFA, ISRAEL SP Chemoprevent Branch, Div Canc Prevent, Control Natl Canc Inst, Israel Canc Assoc, Univ Michigan DE selective estrogen receptor modulators; SERMs; aromatase inhibitors; isoflavones; ovarian-pituitary axis; bone turnover; lipid metabolism; endometrium ID HORMONE REPLACEMENT THERAPY; CARDIOVASCULAR RISK-FACTORS; ADJUVANT TAMOXIFEN THERAPY; CORONARY HEART-DISEASE; BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; MENSTRUAL-CYCLE; RANDOMIZED TRIAL; SOY PROTEIN; AROMATASE INHIBITORS AB Tamoxifen has proven to be beneficial in the chemoprevention of breast cancer in women at increased risk For the disease. Other compounds that mediate the estrogen pathway remain to be tested for clinical efficacy. The mechanism of action, efficacy, and dose response of the estrogen modulators is determined by the hormonal milieu of the host which should be considered in the early clinical trials for dose range finding studies and surrogate endpoint biomarker (SEB) evaluation. This review presents the hormonal effects to consider in the clinical testing of an agent in premenopausal vs. postmenopausal cohorts. Recommended SEBs that may be evaluated in Phase I/II clinical trials of estrogen modulators for breast cancer chemoprevention are presented. J. Cell. Biochem. Suppl. 34:103-114, 2000. (C) 2000 Wiley-Liss, Inc. C1 NCI, Chemoprevent Branch, Div Canc Prevent, Bethesda, MD 20892 USA. CCS Associates, Mountain View, CA USA. RP Lawrence, JA (reprint author), NCI, Chemoprevent Branch, Div Canc Prevent, Execut Plaza N,Suite 201,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 135 TC 1 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 EI 1097-4644 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 2000 SU 34 BP 103 EP 114 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 298YV UT WOS:000086169600017 PM 10762022 ER PT J AU Koehler-Stec, EM Li, K Maher, F Vannucci, SJ Smith, CB Simpson, IA AF Koehler-Stec, EM Li, K Maher, F Vannucci, SJ Smith, CB Simpson, IA TI Cerebral glucose utilization and glucose transporter expression: Response to water deprivation and restoration SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE deoxyglucose; GLUT1; GLUT3; hypothalamoneurohypophysial system; energy metabolism; glucose transport ID MESSENGER-RNA; GENE-EXPRESSION; RAT-BRAIN; CAPILLARY DENSITY; NEURAL LOBE; BC1 RNA; GLUT1; PROTEINS; SYSTEM; TRANSCRIPTION AB The relationship between local rates of cerebral glucose utilization (lCMR(glc)) and glucose transporter expression was examined during physiologic activation of the hypothalamoneurohypophysial system. Three days of water deprivation, which is known to activate the hypnthalamoneurohypophysial system, resulted in increased lCMR(glc) and increased concentrations of GLUT1 and GLUT3 in the neurohypophysis; mRNA levels of GLUT1 and GLUT3 were decreased and increased, respectively. Water deprivation also increased lCMR(glc) in the hypothalamic supraoptic and paraventricular nuclei; mRNA levels of GLUT1 and GLUT3 appeared to increase in these nuclei, but the changes did not achieve statistical significance. Restoration of water for 3 to 7 days reversed all observed changes in GLUT expression (protein and mRNA); restoration of water also reversed changes in lCMR(glc) in both the neurohypophysis and the hypothalamic nuclei. These results indicate that under conditions of neural activation and recovery, changes in lCMR(glc) and the levels of GLUT1 and GLUT3 an temporally correlated in the neurohypophysis and raise the possibility that GLUT1 and GLUT3 transporter expression may be regulated by chronic changes in functional activity. In addition, increases in the expression of GLUT5 mRNA in the neurohypophysis after dehydration provide evidence for involvement of microglial activation. C1 NIDDK, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. RP Simpson, IA (reprint author), NIDDK, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bldg 10,Room 5N102,10 Ctr Dr,MSC 1420, Bethesda, MD 20892 USA. NR 49 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2000 VL 20 IS 1 BP 192 EP 200 DI 10.1097/00004647-200001000-00024 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 281PJ UT WOS:000085169600024 PM 10616808 ER PT J AU Daly, JW Garraffo, HM Jain, P Spande, TF Snelling, RR Jaramillo, C Rand, AS AF Daly, JW Garraffo, HM Jain, P Spande, TF Snelling, RR Jaramillo, C Rand, AS TI Arthropod-frog connection: Decahydroquinoline and pyrrolizidine alkaloids common to microsympatric myrmicine ants and dendrobatid frogs SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE alkaloids; coccinellines; decahydroquinolines; indolizidines; pyrrolidines; pyrrolizidines; dendrobatid frogs; myrmicine ants; coccinellid beetles; millipedes ID DIETARY ALKALOIDS; SKIN ALKALOIDS AB Neotropical poison frogs (Dendrobatidae) contain a wide variety of lipophilic alkaloids, apparently accumulated unchanged into skin glands from dietary sources. Panamanian poison frogs (Dendrobates auratus) raised in a large, screened, outdoor cage and provided for six months with leaf-litter from the frog's natural habitat, accumulated a variety of alkaloids into the skin. These included two isomers of the ant pyrrolizidine 251K; two isomers of the 3,5-disubstituted indolizidine 195B; an alkaloid known to occur in myrmicine ants; another such indolizidine, 211E; two pyrrolidines, 197B and 223N, the former known to occur in myrmicine ants; two tricyclics, 193C and 219I, the former known to occur as precoccinelline in coccinellid beetles; and three spiropyrrolizidines, 222, 236, and 252A, representatives of an alkaloid class known to occur in millipedes. The alkaloids 211E, 197B, and 223N appear likely to derive in part from ants that entered the screened cage. In addition, the frog skin extracts contained trace amounts of four alkaloids, 205D, 207H, 219H, and 231H, of unknown structures and source. Wild-caught frogs from the leaf-litter site contained nearly 40 alkaloids, including most of the above alkaloids. Pumiliotoxins and histrionicotoxins were major alkaloids in wild-caught frogs, but were absent in captive-raised frogs. Ants microsympatric with the poison frog at the leaf-litter site and at an island site nearby in the Bay of Panama were examined for alkaloids. The decahydroquinoline (-)-cis-195A and two isomers of the pyrrolizidine 251K were found to be shared by microsympatric myrmicine ants and poison frogs. The proportions of the two isomers of 251K were the same in ant and frog. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Los Angeles Cty Museum Nat Hist, Los Angeles, CA 90007 USA. Smithsonian Trop Res Inst, Panama City, Panama. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 16 TC 66 Z9 71 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0098-0331 EI 1573-1561 J9 J CHEM ECOL JI J. Chem. Ecol. PD JAN PY 2000 VL 26 IS 1 BP 73 EP 85 DI 10.1023/A:1005437427326 PG 13 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA 284LP UT WOS:000085334100005 ER PT J AU Uttl, B Graf, P Cosentino, S AF Uttl, B Graf, P Cosentino, S TI Exacting assessments: Do older adults fatigue more quickly? SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Psychological-Society CY JUN, 1999 CL DENVER, COLORADO SP Amer Psychol Soc ID LIFE-SPAN; TEST-PERFORMANCE; AGE-DIFFERENCES; IQ GAINS; INTELLIGENCE; DEPRESSION; AMERICANS; CHILDREN; DEMENTIA; MEMORY AB To determine whether neuropsychological testing is fatiguing, and whether it is more fatiguing to older than younger adults, 351 healthy, community living adults, between 18 and 91 years of age, completed a 3 to 4 hour battery of tests focusing on sensation, perception, attention, memory and knowledge. The battery included 3 critical tests: one for assessing the speed of making simple reactions and two for assessing the speed of making decisions. For half of the participants, the critical tests were administered only once, at the end of the session; for the remaining participants, the critical tests were given at the beginning and end of the session. The results show no evidence of fatigue effects with participants from any age group. In view of the type and variety of instruments in our battery, we believe our results will generalize to a wide range of testing situations. The participants in our study were healthy adult volunteers, however, and thus we recommend caution in generalizing the results to clinical populations. C1 Oregon State Univ, Dept Psychol, Corvallis, OR 97331 USA. Univ British Columbia, Dept Psychol, Vancouver, BC V5Z 1M9, Canada. Drexel Univ, Psychol Sociol & Anthropol Dept, Philadelphia, PA USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Uttl, B (reprint author), Oregon State Univ, Dept Psychol, 204C Moreland Hall, Corvallis, OR 97331 USA. NR 42 TC 12 Z9 12 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2000 VL 22 IS 4 BP 496 EP 507 DI 10.1076/1380-3395(200008)22:4;1-0;FT496 PG 12 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 340TE UT WOS:000088550400007 PM 10923059 ER PT J AU Sarlis, NJ Chanock, SJ Nieman, LK AF Sarlis, NJ Chanock, SJ Nieman, LK TI Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the Endocrine-Society CY JUN 21-29, 1998 CL NEW ORLEANS, LA SP Endocrine Soc ID PNEUMOCYSTIS-CARINII-PNEUMONIA; CORTICOTROPIN-RELEASING HORMONE; DEXAMETHASONE-SUPPRESSION TEST; ISLET CELL-CARCINOMA; OPPORTUNISTIC INFECTIONS; DIFFERENTIAL-DIAGNOSIS; GLUCOCORTICOID THERAPY; COMPLICATIONS; DISEASES; CANCER AB Because high circulating levels of glucocorticoids impair immunity and predispose to infections, we evaluated whether indices of cortisol (F) production could predict infections in patients with Cushing syndrome (GS) caused by ectopic production of ACTH (EA). Charts of 54 consecutive patients with untreated EA, without underlying diagnosis of small cell carcinoma of the lung, were reviewed, and types of infections, white blood cell (WBC) count, fever, as well as the glucocorticoid indices [0800 h F, daily urine F excretion (UFC), and daily urine 17-hydroxysteroid/g creatinine excretion (17OHS)], were recorded. Thirty-five patients had no or clinically mild infection; the remaining 19 patients had severe, systemic infection (n = 13) and/or sepsis (n = 6), including either bacterial or opportunistic pathogens or both (73.7%, 42.1%, and 13.8%, respectively). The latter group of patients had significantly higher indices of hypercortisolism (F, UFC, and 17OHS) than those with mild or no infections, but these indices did not correlate with temperature or WBC count. Thresholds for identifying severe infection were selected for maximal positive predictive value and were: F, 43.1 mu g/dL; UFC, 2000 mu g/day; and 17OHS, 35 mg/g creatinine. The most accurate discriminator for severe infection was 17OHS, based on a positive predictive value of 64.7%. Our data strongly suggests that the likelihood for a bacterial or opportunistic infection in CS patients, even without underlying small cell carcinoma of the lung, is greatest in patients with extreme hypercortisolism. The predictive value of total WBC count or the presence of an elevated temperature is not sufficient to identify patients with severe, life-threatening infection. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 9S261,10 Ctr Dr,MSC 1834, Bethesda, MD 20892 USA. EM niemanl@nih.gov NR 42 TC 82 Z9 85 U1 1 U2 5 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 JAN PY 2000 VL 85 IS 1 BP 42 EP 47 DI 10.1210/jc.85.1.42 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272CP UT WOS:000084633200008 PM 10634361 ER PT J AU Goebel, SU Heppner, C Burns, AL Marx, SJ Spiegel, AM Zhuang, ZP Lubensky, IA Gibril, F Jensen, RT Serrano, J AF Goebel, SU Heppner, C Burns, AL Marx, SJ Spiegel, AM Zhuang, ZP Lubensky, IA Gibril, F Jensen, RT Serrano, J TI Genotype/phenotype correlation of multiple endocrine neoplasia type 1 gene mutations in sporadic gastrinomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ZOLLINGER-ELLISON-SYNDROME; TUMOR-SUPPRESSOR GENE; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; MEDULLARY-THYROID CARCINOMA; RET PROTOONCOGENE; MEN1 GENE; METASTATIC GASTRINOMAS; GERMLINE MUTATIONS; DUODENAL GASTRINOMAS; SURGICAL-MANAGEMENT AB Multiple endocrine neoplasia type 1 (MEN1) gene mutations are reported in some gastrinomas occurring in patients without MEN1 as well as in some other pancreatic endocrine tumors (PETs). In some inherited syndromes phenotype-genotype correlations exist for disease severity, location, or other manifestations. The purpose of the present study was to correlate mutations of the MEN1 gene in a large cohort of patients with sporadic gastrinomas to disease activity, tumor location, extent, and growth pattern. DNA was extracted from frozen gastrinomas from 51 patients and screened by dideoxyfingerprinting (ddF) for abnormalities in the 9 coding exons and adjacent splice junctions of the MEN1 gene. Tumor DNA exhibiting abnormal ddF patterns was sequenced for mutations. The findings were correlated with clinical manifestations of the disease, primary tumor site, disease extent, and tumor growth postoperatively. Tumor growth was determined by serial imaging studies. Sixteen different MEN1 gene mutations in the 51 sporadic gastrinomas (31%) were identified (11 truncating, 4 missense, and 1 in-frame deletion). Nine of the 16 mutations were located in exon 2 compared to 7 of 16 in the remaining 8 coding exons (P = 0.005 on a per nucleotide basis). Primary pancreatic or lymph node gastrinomas with a mutation had only exon 2 mutations, whereas duodenal tumors uncommonly harbored exon 2 mutations (P = 0.011). Similarly, small primary tumors (<1 cm) more frequently contained a nonexon 2 mutation (P = 0.02). There was no difference between patients with or without a mutation with respect to clinical characteristics, primary tumor site, disease extent, or proportion of patients disease free after surgery. Postoperative tumor growth tended to be more aggressive inpatients with a mutation (P = 0.09). No correlation in the rate of disease-free status or postoperative tumor growth in patients with active disease to the location of the mutation was seen. These results demonstrate that the MEN1 gene is mutated in 31% of sporadic gastrinomas, and mutations are clustered between amino acids 66 - 166, which differs from patients with familial MEN1, in whom mutations occur throughout the gene. The presence of an MEN1 gene mutation does not correlate with clinical characteristics of patients with gastrinomas, gastrinoma extent, or growth pattern; however, the location of the mutation differed with gastrinoma location. These data suggest that mutations in the MEN1 gene are important in a proportion of sporadic gastrinomas, but the presence or absence of these mutations will not identify the clinically important subgroups with different growth patterns. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 66 TC 67 Z9 69 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 JAN PY 2000 VL 85 IS 1 BP 116 EP 123 DI 10.1210/jc.85.1.116 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272CP UT WOS:000084633200021 PM 10634374 ER PT J AU Rotman-Pikielny, P Reynolds, JC Barker, WC Yen, PM Skarulis, MC Sarlis, NJ AF Rotman-Pikielny, P Reynolds, JC Barker, WC Yen, PM Skarulis, MC Sarlis, NJ TI Recombinant human thyrotropin for the diagnosis and treatment of a highly functional metastatic struma ovarii SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 71st Annual Meeting of the American-Thyroid-Association CY SEP 16-20, 1998 CL PORTLAND, OR SP Amer Thyroid Assoc ID DIFFERENTIATED THYROID-CANCER; RADIOIODINE I-131 THERAPY; RADIATION HEPATITIS; RADIOACTIVE IODINE; CARCINOMA; MANAGEMENT; HORMONE; RADIOTHERAPY; DOSIMETRY; THYROTOXICOSIS AB The optimal treatment of metastatic thyroid cancer that produces high amounts of thyroid hormone has not been well defined. A 46-yr-old woman presented with a follicular thyroid carcinoma arising from a struma ovarii with hepatic metastases. After the removal of both the struma and the thyroid gland, the liver metastases showed evidence of a high degree of hormonogenesis. Brain, chest, abdomen, and bone imaging was negative for additional metastases. Because iodine uptake by most thyroid carcinomas is quite low in the absence of high levels of ambient TSH, we used recombinant human TSH (rhTSH) (Thyrogen) to achieve a concentration of I-131 activity in the tumor high enough for a significant cytotoxic effect. After rhTSH administration (0.9 mg im daily for 2 consecutive days), a I-131 diagnostic whole body scan confirmed the existence of 17 discrete hepatic fool of I-131 uptake. To calculate the amount of I-131 that would deliver an absorbed radiation dose that would be optimally cytotoxic to the metastases (>8000 rad/lesion) and not. to the normal liver, we performed lesion dosimetry. Analysis of dosimetric data showed that 15 of 17 lesions would receive an adequate radiation dose following the administration of 65 mCi of I-131. Additionally, we performed whole body dosimetry to assure that this dose would not cause bone marrow toxicity. The patient was reevaluated 6 months after therapy; the liver metastases showed significant, but partial, response. In conclusion, we used the combination of rhTSH with lesional and whole body dosimetry for the treatment of highly functional metastases from follicular thyroid carcinoma arising within a struma ovarii. This strategy can be applied to determine a safe and effective dose of I-131 for the treatment of any thyroid cancer metastases that produce enough TH to preclude stimulation of endogenous pituitary TSH secretion. C1 NIH, Clin Endocrinol Branch, NIDDK, Bethesda, MD 20892 USA. NIH, Div Intramural Res, NIDDK, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), NIH, Clin Endocrinol Branch, NIDDK, Bldg 10,Room 8D12C,10 Ctr Dr,MSC 1758, Bethesda, MD 20892 USA. EM njsarlis@helix.nih.gov RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 60 TC 43 Z9 47 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 JAN PY 2000 VL 85 IS 1 BP 237 EP 244 DI 10.1210/jc.85.1.237 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272CP UT WOS:000084633200041 PM 10634393 ER PT J AU Chuman, Y Zhan, ZR Fojo, T AF Chuman, Y Zhan, ZR Fojo, T TI Construction of gene therapy vectors targeting adrenocortical cells: Enhancement of activity and specificity with agents modulating the cyclic adenosine 3 ',5 '-monophosphate pathway SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VIRUS THYMIDINE KINASE; CYTOSINE DEAMINASE; ADRENAL Y1; IN-VIVO; EXPRESSION; CARCINOMA; P450SCC; IDENTIFICATION; TRANSCRIPTION; SEQUENCES AB In preliminary studies we demonstrated that the CYP11B1 (11 beta-hydroxylase) promoter could direct specific expression of a suicide gene in adrenocortical cancer cells, providing a potentially specific therapeutic option for adrenocortical cancer. In this present study we describe our attempts to enhance the activity of the CYP11B1 promoter while maintaining its specificity for adrenal cells. Using a putative enhancer element from the cholesterol side-chain cleavage (P450scc) gene, the activity of the CYP11B1 promoter in and its specificity for adrenocortical cells were enhanced. Treatment with 8-bromo-cAMP or forskolin resulted in further enhancement. In stably transfected Y-1 cells, in which the herpes simplex virus thymidine kinase (HSV-TK) gene was driven by the CYP11B1 promoter with the P450scc enhancer element, HSV-TK expression and ganciclovir sensitivity were augmented by treatment with 8-bromo-cAMP, forskolin, and ACTH. In summary, we report the construction of a suicide HSV-TK vector with preferential toxicity to adrenocortical cells. We propose that a similar strategy using differentiating agents may be useful in the gene therapy of tumors with unique differentiated properties, including those arising from other endocrine organs. C1 NIH, Med Branch, Div Clin Sci, NCI, Bethesda, MD 20892 USA. RP Chuman, Y (reprint author), Kagoshima Univ, Dept Surg 1, Fac Med, Sakuragaoka 8-35-1, Kagoshima 8908520, Japan. NR 24 TC 12 Z9 12 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 JAN PY 2000 VL 85 IS 1 BP 253 EP 262 DI 10.1210/jc.85.1.253 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272CP UT WOS:000084633200044 PM 10634396 ER PT J AU Slayden, OD Rubin, JS Lacey, DL Brenner, RM AF Slayden, OD Rubin, JS Lacey, DL Brenner, RM TI Effects of keratinocyte growth factor in the endometrium of rhesus macaques during the luteal-follicular transition SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EPITHELIAL-CELLS; DIFFERENTIAL EXPRESSION; PROGESTIN RECEPTORS; REPRODUCTIVE-TRACT; ESTROGEN-RECEPTORS; PROTEIN-KINASE; MESSENGER-RNA; KGF RECEPTOR; APOPTOSIS; ACTIVATION AB We previously reported that keratinocyte growth factor (KGF) is up-regulated by the action of progesterone (P) in the primate endometrium, and we suggested that this protein is a likely mediator of P-dependent stromal-epithelial paracrine interactions in this tissue. At the end of the menstrual cycle, P levels fall, and the abundance of endometrial KGF transcripts decreases approximately 9-fold. In macaques, withdrawal of P induces the luteal-follicular transition (LFT), marked by menstrual sloughing of the functionalis zone and apoptotic regression of the basalis zone. Because KGF levels fall so dramatically during the LFT, we hypothesized that replacement with exogenous KGF during the LFT would prevent some of the endometrial changes seen after P withdrawal. Here we describe two studies of the effects of exogenously administered KGF during the LFT in rhesus macaques. In one experiment we administered KGF systemically to ovariectomized, juvenile rhesus macaques during an LFT induced by hormonal manipulations. KGF had dramatic proliferative effects on the bladder and salivary glands, known targets of KGF, but did not affect cell proliferation in the endometrium or block menstrual sloughing and bleeding. However, KGF strongly inhibited apoptosis in the basalis zone, increased glandular sacculation and folding in this zone, and had a marked trophic effect on the spiral arteries. In the second experiment we installed oviductal catheters in ovariectomized adult rhesus macaques and infused KGF directly into the uterine lumen during a hormonally induced LFT. Again, arteriotrophic, antiapoptotic, and basalis gland sacculation effects were observed in the absence of any effect on cell proliferation. We concluded that although KGF is mitogenic for many epithelial cell types, it does not play this role in the primate endometrium. Its most important roles may be to stimulate spiral artery growth and inhibit glandular apoptosis during the nonfertile menstrual cycle. Because its expression rises coincident with the time of implantation and because spiral arteries are essential to successful establishment of pregnancy, the role of KGF in the fertile menstrual cycle deserves further study. C1 Oregon Reg Primate Res Ctr, Div Repord Sci, Beaverton, OR 97006 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Slayden, OD (reprint author), Oregon Reg Primate Res Ctr, Div Repord Sci, Beaverton, OR 97006 USA. FU NICHD NIH HHS [HD-07675, HD-19182, P30-HD-18185] NR 41 TC 20 Z9 21 U1 0 U2 2 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 JAN PY 2000 VL 85 IS 1 BP 275 EP 285 DI 10.1210/jc.85.1.275 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 272CP UT WOS:000084633200047 PM 10634399 ER PT J AU Burt, RK Brenner, M Burns, W Courier, E Firestein, G Hahn, B Heslop, H Link, C McFarland, H Roland, M Territo, M Tsokos, G Traynor, A AF Burt, RK Brenner, M Burns, W Courier, E Firestein, G Hahn, B Heslop, H Link, C McFarland, H Roland, M Territo, M Tsokos, G Traynor, A TI Gene-marked autologous hematopoietic stem cell transplantation of autoimmune disease SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE hematopoietic stem cell transplantation; gene-marked autologous stem cells; autoimmune disease ID SYSTEMIC LUPUS-ERYTHEMATOSUS; FLUORESCENT PROTEIN GENE; RHEUMATOID-ARTHRITIS; PERIPHERAL-BLOOD; MULTIPLE-SCLEROSIS; ANTIGEN RECEPTOR; T-LYMPHOCYTES; TARGET-CELLS; TRANSDUCTION; EXPRESSION AB In phase I(safety) trials, we have demonstrated the feasibility of autologous hematopoietic stem cell transplantation (HSCT) for patients with autoimmune diseases. Although this review comments on results of our phase I trials, the focus is on phase II (efficacy) trials using gene-marked autologous stem cells. C1 Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. Rupert H Lurie Canc Ctr, Chicago, IL 60611 USA. Baylor Coll Med, Cell & Gene Therapy Ctr, Houston, TX 77030 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Human Gene Therapy Res Inst, Des Moines, IA USA. NIH, Bethesda, MD 20892 USA. Henry M Jackson Fdn Advancement Mil Sci, Rockville, MD USA. RP Burt, RK (reprint author), Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. NR 41 TC 11 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JAN PY 2000 VL 20 IS 1 BP 1 EP 9 DI 10.1023/A:1006673408343 PG 9 WC Immunology SC Immunology GA 309JK UT WOS:000086764600001 PM 10798601 ER PT J AU Huang, CA Fuchimoto, Y Scheier-Dolberg, R Murphy, MC Neville, DM Sachs, DH AF Huang, CA Fuchimoto, Y Scheier-Dolberg, R Murphy, MC Neville, DM Sachs, DH TI Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; T-CELL DEPLETION; MAJOR HISTOCOMPATIBILITY COMPLEX; TOTAL-BODY IRRADIATION; VS-HOST DISEASE; MINIATURE SWINE; ALLOGENEIC CHIMERAS; ANKYLOSING-SPONDYLITIS; MONOCLONAL-ANTIBODIES; RADIATION CHIMAERAS AB Bone marrow transplantation (BMT) has considerable potential for the treatment of malignancies, hemoglobinopathies, and autoimmune diseases, as well as the induction of transplantation allograft tolerance. Toxicities associated with standard preparative regimens for bone marrow transplantation, however make this approach unacceptable for all but the most severe of these clinical situations. Here, we demonstrate that stable mixed hematopoietic cell chimerism and donor-specific tolerance can be established in miniature swine, using a relatively mild, non-myeloablative preparative regimen. We conditioned recipient swine with whole-body and thymic irradiation, and we depleted their T-cells by CD3 immunotoxin-treatment. Infusion of either bone marrow cells or cytokine-mobilized peripheral blood stem cells from leukocyte antigen-matched animals resulted in stable mixed chimerism, as detected by flow cytometry in the peripheral blood, thymus, and bone marrow, without any clinical evidence of graft-versus-host disease (GvHD). Long-term acceptance of donor skin and consistent rejection of third-party skin indicated that the recipients had developed donor-specific tolerance. C1 Massachusetts Gen Hosp, Tranplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Tranplantat Biol Res Ctr, MGH East,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [1RO1 HL-63430, 5RO1 HL-46532] NR 37 TC 152 Z9 159 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2000 VL 105 IS 2 BP 173 EP 181 DI 10.1172/JCI7913 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 275HX UT WOS:000084815700006 PM 10642595 ER PT J AU Kido, Y Burks, DJ Withers, D Bruning, JC Kahn, CR White, MF Accili, D AF Kido, Y Burks, DJ Withers, D Bruning, JC Kahn, CR White, MF Accili, D TI Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DEPENDENT DIABETES-MELLITUS; GROWTH-FACTOR-I; PHOSPHOTYROSINE PROTEIN; GLUCOSE-TOLERANCE; SUBSTRATE FAMILY; NIDDM; DISRUPTION; MUSCLE; TRAITS; MEMBER AB Type 2 diabetes is characterized by abnormalities of insulin action in muscle, adipose tissue, and Liver and by altered beta-cell function. To analyze the role of the insulin signaling pathway in these processes, we have generated mice with combined heterozygous null mutations in insulin receptor (ir), insulin receptor substrate (irs-1), and/or irs-2. Diabetes developed in 40% of ir/irs-1/irs-2(+/-), 20% of ir/irs-1(+/-), 17% of ir/irs-2(+/-), and 5% of ir(+/-) mice. Although combined heterozygosity for ir/irs-1(+/-) and ir/irs-2(+/-) results in a similar number of diabetic mice, there are significant differences in the underlying metabolic abnormalities. ir/irs-1(+/-) mice develop severe insulin resistance in skeletal muscle and liver, with compensatory beta-cell hyperplasia, In contrast, ir/irs-2(+/-) mice develop severe insulin resistance in liver, mild insulin resistance in skeletal muscle, and modest beta-cell hyperplasia. Triple heterozygotes develop severe insulin resistance in skeletal muscle and liver and marked beta-cell hyperplasia. These data indicate tissue-specific differences in the roles of IRSs to mediate insulin action, with irs-1 playing a prominent role in skeletal muscle and irs-2 in Liver. They also provide a practical demonstration of the polygenic and genetically heterogeneous interactions underlying the inheritance of type 2 diabetes. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20842 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Howard Hughes Med Inst, Boston, MA 02215 USA. RP Accili, D (reprint author), Berrie Res Pavil,1150 St Nicholas Ave,Room 238A, New York, NY 10032 USA. RI Withers, Dominic/D-7671-2014 OI Withers, Dominic/0000-0002-8009-7521 NR 39 TC 324 Z9 343 U1 2 U2 17 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2000 VL 105 IS 2 BP 199 EP 205 DI 10.1172/JCI7917 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 275HX UT WOS:000084815700009 PM 10642598 ER PT J AU Hamilton, RS Gravell, M Major, EO AF Hamilton, RS Gravell, M Major, EO TI Comparison of antibody titers determined by hemagglutination inhibition and enzyme immunoassay for JC virus and BK virus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HUMAN POLYOMAVIRUS JC; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; SIMIAN VIRUS-40; SIALIC-ACID; GLIAL-CELLS; PLEURAL MESOTHELIOMA; REGULATORY REGION; IMMUNE-RESPONSE; CHOROID-PLEXUS; DNA-SEQUENCES AB A comparison of antibody titers to JC virus (JCV) or BK virus (BKV) was made by hemagglutination inhibition (HI) and enzyme immunoassay (EIA) with 114 human plasma samples. Antibody titers to JCV or BKV determined by HI were lower than those determined by EIA. Nevertheless, as HI titers increased so did EW titers, When antibody data were compared by the Spearman rank correlation test, highly significant correlations were found between HI and EIA titers, Results obtained by plotting EIA antibody titers for JCV against those for BW generally showed a reciprocal relationship, i.e., samples with high antibody titers to JCV had lower antibody titers to BKV and vice versa, Some samples, however, had antibody titers to both viruses. Of the samples tested, 25.4% (25 of 114) had HI and EIA antibody titers to JCV and BKV which were identical or closely related. This is not the scenario one would expect for cross-reactive epitopes shared by the two viruses, but one suggesting that these samples were from individuals who had experienced infections by both viruses. Adsorption with concentrated JCV or BW antigen of sera with high antibody titers to both JCV and BKV and testing by JCV and BKV EIA gave results which support this conclusion. Although 52.6% (51 of 97) of the samples from the Japanese population tested had very high antibody titers (greater than or equal to 40,960) to either JCV or BW, none of the samples were found by a dot blot immunoassay to have antibodies which cross-reacted with simian virus 40. The results from this study, in agreement with those of others, suggest that humans infected by JCV or BKV produce antibodies to species-specific epitopes on their VP1 capsid protein, which is associated with hemagglutination and cellular binding. C1 NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Gravell, M (reprint author), NINDS, Lab Mol Med & Neurosci, Bldg 36,Rm 5W21,MSC 4164,36 Convent Dr, Bethesda, MD 20892 USA. NR 36 TC 72 Z9 72 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2000 VL 38 IS 1 BP 105 EP 109 PG 5 WC Microbiology SC Microbiology GA 273CN UT WOS:000084689800020 PM 10618072 ER PT J AU Conville, PS Fischer, SH Cartwright, CP Witebsky, FG AF Conville, PS Fischer, SH Cartwright, CP Witebsky, FG TI Identification of Nocardia species by restriction endonuclease analysis of an amplified portion of the 16S rRNA gene SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL-RNA; RAPID IDENTIFICATION; DNA AMPLIFICATION; ASTEROIDES; BRASILIENSIS; RECOGNITION; STRAINS; COMPLEX; TAXA AB Identification of clinical isolates of Nocardia to the species level is important for defining the spectrum of disease produced by each species and for predicting antimicrobial susceptibility. We evaluated the usefulness of PCR amplification of a portion of the Nocardia 16S rRNA gene and subsequent restriction endonuclease analysis (REA) for species identification. Unique restriction fragment length polymorphism (RFLP) patterns were found for Nocardia sp. type strains (except for the N. asteroides type strain) and representative isolates of the drug pattern types of Nocardia asteroides (except for N. asteroides drug pattern type IF: which gave inconsistent amplification). A variant RFLP pattern for Nocardia nova was also observed. Twenty eight clinical isolates were evaluated both by traditional biochemical identification and by amplification and REA of portions of the 16S rRNA gene and the 65-kDa heat shock protein (HSP) gene. There aas complete agreement among the three methods on identification of 24 of these isolates. One isolate gave a 16S rRNA RFLP pattern consistent with the biochemical identification but was not identifiable by its HSP gene RFLP patterns, Three isolates gave 16S rRNA RFLP patterns which were inconsistent with the identification obtained by both biochemical tests and BSP gene RFLP; sequence analysis suggested that mo of these isolates may belong to undefined species, The PCR and REA technique described appears useful both for the identification of clinical isolates of Nocardia and for the detection of new or unusual species. C1 NIH, Microbiol Serv, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Conville, PS (reprint author), NIH, Microbiol Serv, Dept Clin Pathol, Warren Grant Magnuson Clin Ctr, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. NR 19 TC 74 Z9 79 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2000 VL 38 IS 1 BP 158 EP 164 PG 7 WC Microbiology SC Microbiology GA 273CN UT WOS:000084689800028 PM 10618080 ER PT J AU Gravitt, PE Peyton, CL Alessi, TQ Wheeler, CM Coutlee, F Hildesheim, A Schiffman, MH Scott, DR Apple, RJ AF Gravitt, PE Peyton, CL Alessi, TQ Wheeler, CM Coutlee, F Hildesheim, A Schiffman, MH Scott, DR Apple, RJ TI Improved amplification of genital human papillomaviruses SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; YOUNG-WOMEN; INFECTION; RISK AB Genital human papillomaviruses (HPVs) are commonly detected from clinical samples by consensus PCR methods. Two commonly used primer systems, the MY09-MY11 (MY09/11) primers and the GP5+-GP6+ (GP5+/6+) primers, amplify a broad spectrum of HPV genotypes, but with various levels of sensitivity among the HPV types. Analysis of the primer-target sequence homology for the MY09/11 primers showed an association between inefficient amplification of HPV types and the number and position of mismatches, despite accommodation of sequence variation by inclusion of degenerate base sites. The MY09/11 primers were redesigned to increase the sensitivity of amplification across the type spectrum by using the same primer binding regions in the L1 open reading frame. Sequence heterogeneity was accommodated by designing multiple primer sequences that were combined into an upstream pool of 5 oligonucleotides (PGMY11) and a downstream pool of 13 oligonucleotides (PGMY09), thereby avoiding use of degenerate bases that yield irreproducible primer syntheses. The performance of the PGMY09-PGMY11 (PGMY09/11) primer system relative to that of the standard MY09/11 system was evaluated with a set of 262 cervicovaginal lavage specimens. There was a 91.5% overall agreement between the two systems (kappa = 0.83; P < 0.001), The PGMY09/11 system appeared to be significantly more sensitive than the MY09/11 system, detecting an additional 20 HPV-positive specimens, for a prevalence of 62.8% versus a prevalence of 55.1% with the MY09/11 system (McNemar's chi(2) = 17.2; P < 0.001), The proportion of multiple infections detected increased with the PGMY09/11 system (40.0 versus 33.8% of positive infections). HPV types 26, 35, 42, 45, 52, 54, 55, 59, 66, 73, and MM7 were detected at least 25% more often with the PGMY09/11 system. The PGMY09/11 primer system affords an increase in type-specific amplification sensitivity over that of the standard MY09/11 primer system, This new primer system will be useful in assessing the natural history of HPV infections, particularly when the analysis requires HPV typing. C1 Roche Mol Syst, Dept Human Genet, Alameda, CA 94501 USA. Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. CHUM, Dept Microbiol Infectiol, Montreal, PQ, Canada. NCI, Environm Epidemiol Branch, Rockville, MD USA. Kaiser Permanente, Dept Pathol, Portland, OR USA. RP Gravitt, PE (reprint author), 2810 St Paul St 1, Baltimore, MD 21218 USA. RI apple, raymond/I-4506-2012 OI apple, raymond/0000-0002-8007-0345 NR 18 TC 747 Z9 769 U1 3 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2000 VL 38 IS 1 BP 357 EP 361 PG 5 WC Microbiology SC Microbiology GA 273CN UT WOS:000084689800064 PM 10618116 ER PT J AU Schwan, TG Piesman, J AF Schwan, TG Piesman, J TI Temporal changes in outer surface proteins A and C of the Lyme disease-associated spirochete, Borrelia burgdorferi, during the chain of infection in ticks and mice SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IXODES-DAMMINI ACARI; WHITE-FOOTED MICE; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODY; ACTIVE IMMUNIZATION; IMMUNE-RESPONSE; IN-VITRO; OSPA; TRANSMISSION; ARTHROPOD AB The Lyme disease-associated spirochete, Borrelia burgdorferi, is maintained in enzootic cycles involving Ixodes ticks and small, mammals. Previous studies demonstrated that B. Burgdorferi expresses outer surface protein A (OspA) but not OspC when residing in the midgut of unfed ticks. However, after ticks feed on blood, some spirochetes stop making OspA and express OspC, Our current work examined the timing and frequency of OspA and OspC expression by B. burgdorferi in infected Ixodes scapularis nymphs as they fed on uninfected mice and in uninfected I. scapularis larvae and nymphs as they first acquired spirochetes from infected mite. Smears of midguts from previously infected ticks were prepared at 12- or 24-h intervals following attachment through repletion at 96 h, and spirochetes were stained for immunofluorescence for detection of antibodies to OspA and OspC. As shown previously, prior to feeding spirochetes in nymphs expressed OspA but not OspC. During nymphal feeding, however, the proportion of spirochetes expressing OspA decreased, while spirochetes expressing OspC became detectable. In fact, spirochetes rapidly began to express OspC, with the greatest proportion of spirochetes having this protein at 48 h of attachment and then with the proportion decreasing significantly by the time that the ticks had completed feeding. In vitro cultivation of the spirochete at different temperatures showed OspC to be most abundant when the spirochetes were grown at 37 degrees C. Yet, the synthesis of this protein waned with continuous passage at this temperature. Immunofluorescence staining of spirochetes in smears of midguts from larvae and nymphs still attached or having completed feeding on infected mice demonstrated that OspA but not OspC was produced by these spirochetes recently acquired from mice, Therefore, the temporal synthesis of OspC by spirochetes only in feeding ticks that were infected prior to the blood meal suggests that this surface protein is involved in transmission from tick to mammal but not from mammal to tick. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, Ft Collins, CO 80522 USA. RP Schwan, TG (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 47 TC 276 Z9 281 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2000 VL 38 IS 1 BP 382 EP 388 PG 7 WC Microbiology SC Microbiology GA 273CN UT WOS:000084689800068 PM 10618120 ER PT J AU Stark, A Hulka, BS Joens, S Novotny, D Thor, AD Wold, LE Schell, MJ Melton, LJ Liu, ET Conway, K AF Stark, A Hulka, BS Joens, S Novotny, D Thor, AD Wold, LE Schell, MJ Melton, LJ Liu, ET Conway, K TI HER-2/neu amplification in benign breast disease and the risk of subsequent breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; DUCTAL CARCINOMA INSITU; C-ERBB-2 ONCOGENE; MICROSATELLITE ALTERATIONS; PROGNOSTIC FACTORS; COPY NUMBER; C-MYC; EXPRESSION; OVEREXPRESSION; LESIONS AB Purpose: The purpose of this study was to determine whether the presence of HER-2/neu gene amplification and/or overexpression in benign breast disease was associated with an increased risk of subsequent breast cancer. Patients and Methods: We conducted a nested case-control study of a cohort of women who were diagnosed with benign breast disease at the Mayo Clinic and who were subsequently observed for the development of breast cancer, Patients who developed breast cancer formed the case group, and a matched sample from the remaining cohort served as controls. Benign tissue samples from 137 cases and 156 controls and malignant tissues from 99 cases provided DNA or tissue for evaluation of HER-2/neu amplification and protein overexpression, Results: Among the controls, seven benign tissues (4.5%) demonstrated low-level HER-2/neu amplification, whereas 13 benign (9.5%) and 18 malignant (18%) tissue specimens from cases exhibited amplification. HER-2/neu amplification in benign breast biopsies was associated with an increased risk of breast cancer (odds ratio [OR] = 2.2; 95% confidence interval [CI], 0.9 to 5.8); this association approached statistical significance, The risks for breast cancer associated with benign breast histopathologic diagnoses were OR = 1.1 (95% CI, 0.6 to 1.9) for lesions exhibiting proliferation without atypia and OR = 1.5 (95% CI, 0.4 to 5.6) for the diagnosis of atypical ductal hyperplasia, For women having both HER-2/neu amplification and a proliferative histopathologic diagnosis (either typical or atypical), the risk of breast cancer was more than seven-fold (OR = 7.2; 95% CI, 0.9 to 60.8). Overexpression of the HER-2/neu protein product, defined as membrane staining in 10% or more of epithelial cells, was found in 30% of the breast tumors but was not detected in any of the benign breast tissues. Case patients who had HER-2/neu gene amplification in their malignant tumor were more likely to have had HER-2/neu amplification in their prior benign biopsy (P = .06, Fisher's exact test). Conclusion: Women with benign breast biopsies demonstrating both HER-2/neu amplification and a proliferative histopathologic diagnosis may be at substantially increased risk for subsequent breast cancer. (C) 2000 by American Society of Clinical Oncology. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Northwestern Univ, Dept Pathol & Lab Med, Chicago, IL 60611 USA. Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. Natl Canc Inst, Div Clin Sci, Bethesda, MD USA. RP Conway, K (reprint author), Univ N Carolina, Dept Epidemiol, Campus Box 7400,2101 McGavran,Greenberg Hall, Chapel Hill, NC 27599 USA. RI Liu, Edison/C-4141-2008 FU NCI NIH HHS [CA 46332, CA 58223]; NIEHS NIH HHS [T32-ES07018] NR 54 TC 82 Z9 87 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 2 BP 267 EP 274 PG 8 WC Oncology SC Oncology GA 275TK UT WOS:000084836100005 PM 10637239 ER PT J AU Conley, B O'Shaughnessy, J Prindiville, S Lawrence, J Chow, C Jones, E Merino, MJ Kaiser-Kupfer, MI Caruso, RC Podger, M Goldspiel, B Venzon, D Danforth, D Wu, SL Noone, M Goldstein, J Cowan, KH Zujewski, J AF Conley, B O'Shaughnessy, J Prindiville, S Lawrence, J Chow, C Jones, E Merino, MJ Kaiser-Kupfer, MI Caruso, RC Podger, M Goldspiel, B Venzon, D Danforth, D Wu, SL Noone, M Goldstein, J Cowan, KH Zujewski, J TI Pilot trial of the safety, tolerability, and retinoid levels of N-(4-hydroxyphenyl) retinamide in combination with tamoxifen in patients at high risk for developing invasive breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTMENOPAUSAL WOMEN; FENRETINIDE 4-HPR; DARK-ADAPTATION; FEMALE RAT; VITAMIN-A; PREVENTION; GROWTH; CELLS; INHIBITION; METABOLISM AB Purpose: N-(4-hydroxyphenyl) retinamide([4-HPR], Fenretinide; R.W. Johnson Pharmaceutical Research Institute, Springhouse, PA) and tamoxifen (TAM) have synergistic antitumor and chemopreventive activity against mammary cancer in preclinical studies. We performed a pilot study of this combination in women at high risk for developing breast cancer. Patients and Methods: Thirty-two women were treated with four cycles of 4-HPR, 200 mg orally (PO) for 25 days of each 28-day cycle, and TAM, 20 mg PO once daily for 23 months beginning after 1 month of 4-HPR alone. Tolerability, dark adaptometry, tissue biopsies, and retinoid plasma concentrations (Cp) were evaluated. Results: Symptomatic reversible nyctalopia developed in two patients (6%) on 4-HPR, but 16 (73%) of 22 patients had reversible changes in dark adaptation, which correlated with relative decrease in Cp retinol (P less than or equal to .01), Four patients stopped treatment for side effects, and 84% of patients had hot flashes. Other commonly reported (grade less than or equal to 2) reversible toxicities included skin and ocular dryness, fatigue, and mood changes. Serum high-density lipoprotein increased and cholesterol decreased from baseline to month 4. Baseline mean +/- SD Cp retinol was 708 +/- 280 ng/mL. Mean +/- SD Cp of 4-HPR, N-(4-methoxyphenyl) retinamide (4-MPR), and retinol after 1 month of 4-HPR were 0.34 +/- 0.21 mu mol/L, 0.28 +/- 0.21 mu mol/L, and 282 +/- 127 ng/mL, respectively. Mean retinoid Cps did not change after 3 months of Q-HPR + TAM. Conclusions: TAM administration did not affect Cp 4-HPR or 4-MPR. Reversible nyctalopia correlated with relative decrease in Cp retinol but was not symptomatic for most patients. TAM + 4-HPR has acceptable tolerability for this high-risk cohort. (C) 2000 by American Society of Clinical Oncology. C1 Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Div Hematol & Oncol, Baltimore, MD 21201 USA. NEI, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Med Branch, Pathol Lab, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. RP Zujewski, J (reprint author), NCI, Med Branch, Ctr Clin, NIH, Rm 12N226,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 43 TC 50 Z9 51 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 2 BP 275 EP 283 PG 9 WC Oncology SC Oncology GA 275TK UT WOS:000084836100006 PM 10637240 ER PT J AU Socie, G Curtis, RE Deeg, HJ Sobocinski, KA Filipovich, AH Travis, LB Sullivan, KM Rowlings, PA Kingma, DW Banks, PM Travis, WD Witherspoon, RP Sanders, J Jaffe, ES Horowitz, MM AF Socie, G Curtis, RE Deeg, HJ Sobocinski, KA Filipovich, AH Travis, LB Sullivan, KM Rowlings, PA Kingma, DW Banks, PM Travis, WD Witherspoon, RP Sanders, J Jaffe, ES Horowitz, MM TI New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM SURVIVORS; BONE-MARROW; HODGKINS-DISEASE; APLASTIC-ANEMIA; 2ND MALIGNANCIES; THYROID-CANCER; RADIATION; NEOPLASMS; CHILDREN AB Purpose: To determine the incidence of and risk factors for second malignancies after allogeneic bone mar row transplantation (BMT) far childhood leukemia. Patients and Methods: We studied a cohort of 3,182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age and sex-matched general population. Risks factors were evaluated using Poisson regression. Results: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P <.001), Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT, Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7.5), T-cell-depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). Conclusion: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers. (C) 2000 by American Society of Clinical Oncology. C1 Hop St Louis, Serv Hematol Greffe Moelle, F-75475 Paris 10, France. NCI, Pathol Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Pathol Lab, Div Canc Biol & Diag, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Milwaukee, WI 53226 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Curtis, RE (reprint author), Hop St Louis, Serv Hematol Greffe Moelle, 1 Ave Claude Vellefaux, F-75475 Paris 10, France. FU NCI NIH HHS [CP-51028, CP-51027, P01-CA-40053] NR 50 TC 202 Z9 204 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 2 BP 348 EP 357 PG 10 WC Oncology SC Oncology GA 275TK UT WOS:000084836100015 PM 10637249 ER PT J AU Boccardo, F Rubagotti, A AF Boccardo, F Rubagotti, A CA Italian Prostate Canc Project TI Is the use of anti-androgen monotherapy appropriate in patients with advanced prostate cancer? In reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID CASTRATION; SURVIVAL; CASODEX; QUALITY; LIFE C1 Univ Genoa, Genoa, Italy. Natl Canc Inst, Genoa, Italy. RP Boccardo, F (reprint author), Univ Genoa, Genoa, Italy. NR 8 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 2000 VL 18 IS 2 BP 449 EP 450 PG 2 WC Oncology SC Oncology GA 275TK UT WOS:000084836100033 ER PT J AU Alfaro, CL Lam, YWF Simpson, J Ereshefsky, L AF Alfaro, CL Lam, YWF Simpson, J Ereshefsky, L TI CYP2D6 inhibition by fluoxetine, paroxetine, sertraline, and venlafaxine in a crossover study: Intraindividual variability and plasma concentration correlations SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc ID SEROTONIN REUPTAKE INHIBITORS; HUMAN LIVER-MICROSOMES; DRUG-INTERACTIONS; IN-VITRO; ANTIDEPRESSANTS; DESIPRAMINE; METABOLISM; PHARMACOKINETICS; DEXTROMETHORPHAN; QUANTIFICATION AB The authors report the CYP2D6 inhibitory effects of fluoxetine, paroxetine, sertraline, and venlafaxine in an open-label, multiple-dose, crossover design. Twelve CYP2D6 extensive metabolizers were phenotyped, using the dextromethorphan/dextrorphan (DM/DX) urinary ratio, before and after administration of fluoxetine 60 mg (loading dose strategy), paroxetine 20 mg, sertraline 100 mg, and venlafaxine 150 mg Paroxetine, sertraline, and venlafaxine sequences were ran; domized with 2-week washouts between treatments; fluoxetine was the last antidepressant (AD) administered. Comparing within groups, baseline DM/DX ratios (0.017) were significantly lower than DM/DX ratios after treatment (DM/DXAD) with fluoxetine (0.313, p < 0.0001) and paroxetine (0.602, p < 0.0001) but not for sertraline (0.026, p = 0.066) or venlafaxine (0.023, p = 0.485). Between groups, DM/DXAD ratios were significantly higher for fluoxetine and paroxetine compared to sertraline and venlafaxine. No differences between DM/DXAD ratios were found for fluoxetine and paroxetine although more subjects phenocopied to PM status. after receiving the latter (42% vs. 83%; chi(2) = 4.44, p = 0.049, df = 1). Similarly, no differences between DM/DXAD ratios were found for sertraline and venlafaxine. Of note, the DM/DXAD for 1 subject was much lower after treatment with paroxetine (0.058) compared to fluoxetine (0.490), while another subject exhibited a much lower ratio after treatment with fluoxetine (0.095) compared to paroxetine (0.397). Significant correlations between RD plasma concentration and DM/DXAD were found for paroxetine (r(2) = 0.404, p = 0.026) and sertraline (r(2) = 0.64, p = 0.002) but not fluoxetine or venlafanine. In addition, DM/DXAD correlated with baseline isoenzyme activity for paroxetine, sertraline, and venlafaxine groups. These results demonstrate the potent, but. variable, CYP2D6 inhibition of fluoxetine and paroxetine compared to sertraline and venlafaxine. CYP2D6 inhibition may be related, in part to dose, plasma concentration, and baseline isoenzyme activity, and these correlations merit further investigation. (C) 2000 the American College of Clinical Pharmacology. C1 Univ Texas, Hlth Sci Ctr, Pharmacotherapy Div, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Coll Pharm, Austin, TX 78712 USA. Alamo Mental Hlth Grp, San Antonio, TX USA. NIH, Hlth Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. RP Ereshefsky, L (reprint author), Univ Texas, Hlth Sci Ctr, Pharmacotherapy Div, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 35 TC 91 Z9 96 U1 3 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JAN PY 2000 VL 40 IS 1 BP 58 EP 66 DI 10.1177/00912700022008702 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 269FH UT WOS:000084465700008 PM 10631623 ER PT J AU Frye, MA Ketter, TA Leverich, GS Huggins, T Lantz, C Denicoff, KD Post, RM AF Frye, MA Ketter, TA Leverich, GS Huggins, T Lantz, C Denicoff, KD Post, RM TI The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 149th Annual Meeting of the American-Psychiatric-Association CY MAY 04-09, 1996 CL NEW YORK, NEW YORK SP Amer Psychiat Assoc ID BIPOLAR AFFECTIVE-DISORDER; MANIC-DEPRESSIVE ILLNESS; ANTIRETROVIRAL THERAPY; MAJOR DEPRESSION; LITHIUM; LAMOTRIGINE; EFFICACY; CARBAMAZEPINE; PROPHYLAXIS; VALPROATE AB Background: Few studies have approached the subject of polypharmacotherapy systematically. This retrospective review of 178 patients with refractory bipolar disorder or unipolar depression (Research Diagnostic Criteria or DSM-III-R criteria) discharged from the National Institute of Mental Health (NIMH) Biological Psychiatry Branch between 1974 and 1996 was conducted to assess the degree and efficacy of "add-on" pharmacotherapy. Method: Following completion of formal structured blinded research protocols, patients entered a treatment phase (often again on a blind basis) in which all agents available in the community could be utilized. Each patient's retrospective life chart and all prospective double-blind nurse- and self-rated NIMH data were reviewed. The overall degree of improvement at discharge was assessed by rating on the Clinical Global Impressions scale (CGI) as modified for bipolar illness (CGI-BP). Results: A 78% improvement rate (moderate or marked on the CGI) was achieved at the time of discharge. There was a significant relationship between number of medications utilized at discharge as a function of discharge date (r = 0.45, p < .0001). The percentages of patients discharged on treatment with 3 or more medications were 3.3% (1974-1979), 9.3% (1980-1984), 34.9% (1985-1989), and 43.8% (1990-1995), No correlation was found between polypharmacy and age (r = -0.03, p = .66). Patients more recently discharged from the NIMH had an earlier age at illness onset, more lifetime weeks depressed, and a higher rate of rapid cycling than patients in the earlier cohorts. Conclusion: Increasing numbers of medications in more recent NIMH cohorts were required to achieve the same degree of improvement at hospital discharge. More systematic approaches to the complex regimens required for treatment of patients with refractory mood disorder are clearly needed. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, Bldg 10,Room 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 63 TC 179 Z9 179 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2000 VL 61 IS 1 BP 9 EP 15 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 285RY UT WOS:000085402900003 PM 10695639 ER PT J AU Giedd, JN AF Giedd, JN TI Bipolar disorder and attention-deficit/hyperactivity disorder in children and adolescents SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; CHILDHOOD-ONSET SCHIZOPHRENIA; BASAL GANGLIA VOLUMES; CORPUS-CALLOSUM; MRI ANALYSIS; FOLLOW-UP; MANIA; PREVALENCE; HYPERINTENSITIES; ABNORMALITIES AB The relationship between bipolar disorder and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents has been one of the most hotly debated topics in recent child psychiatry literature. At the heart of the matter is whether large numbers of children with bipolar disorder are being unrecognized or misdiagnosed. The differential diagnoses of juvenile-onset bipolar disorder can be complicated by many factors, but the most common clinical dilemmas seem to arise from overlapping symptomatology with ADHD and the differing treatment strategies these diagnoses imply. This article discusses the similarities and differences between these disorders with respect to phenomenology, epidemiology, family history, brain imaging, and treatment response. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 4C110,10 Ctr Dr,MSC 1367, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 60 TC 34 Z9 34 U1 14 U2 17 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2000 VL 61 SU 9 BP 31 EP 34 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 314YQ UT WOS:000087085500005 PM 10826658 ER PT J AU Manji, HK Lenox, RH AF Manji, HK Lenox, RH TI The nature of bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Bipolar Disorder Advisory Summit CY AUG 13-15, 1999 CL NEW YORK, NEW YORK SP Janssen Pharmaceutica ID PROTEIN-KINASE-C; MANIC-DEPRESSIVE ILLNESS; LONG-TERM LITHIUM; PLATELET MEMBRANE PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE; IMMORTALIZED HIPPOCAMPAL CELLS; SIGNAL-TRANSDUCTION PATHWAYS; RECEPTOR-MEDIATED ACTIVATION; ENDOGENOUS ADP-RIBOSYLATION; CYCLIC-AMP; ADENYLATE-CYCLASE AB The underlying pathophysiology of bipolar disorder is a continually evolving complexity of multilayer interacting and independent systems. The dearth of adequate preclinical or clinical models that incorporate the various features of the illness, i.e., acute and chronic, recurrent and episodic, and timecourse and treatment-related variables, has made the consistency and interpretation of data difficult. Newer technologies and the availability of structurally and mechanistically distinct pharmacologic agents have expanded opportunities for experimental study. In addition to the well-known neurotransmitter systems that are disrupted in mood disorders, critical guanine nucleotide-binding protein (G protein)-coupled signaling pathways are implicated in modulating mood state. Regulation of gene expression and identification of factors regulating neuroplasticity and neurotrophic events in the central nervous system in bipolar disorder are 2 of the more recent approaches contributing to clarification of the pathophysiology and potential treatment options. C1 Wayne State Univ, Mol Pathophysiol Lab, Dept Psychiat & Behav Neurosci, Detroit, MI 48202 USA. Wayne State Univ, Mol Pathophysiol Lab, Dept Pharmacol, Cellular & Clin Neurobiol Program, Detroit, MI 48202 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, 49 Convent Dr,MSC 4405,Bldg 49,Room B1EE16, Bethesda, MD 20892 USA. FU NIMH NIH HHS [R01-MH6247, R01-MH57743, R01-MH59107] NR 142 TC 69 Z9 69 U1 1 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2000 VL 61 SU 13 BP 42 EP 57 PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 388ZB UT WOS:000166212000007 PM 11153812 ER PT J AU Brotman, MA Fergus, EL Post, RM Leverich, GS AF Brotman, MA Fergus, EL Post, RM Leverich, GS TI High exposure to neuroleptics in bipolar patients: A retrospective review SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 151st Annual Meeting of the American-Psychiatric-Association CY MAY 30-JUN 05, 1998 CL TORONTO, CANADA SP Amer Psychiat Assoc ID MANIC-DEPRESSIVE ILLNESS; TARDIVE-DYSKINESIA; AFFECTIVE-DISORDER; MOOD DISORDERS; LITHIUM; INTERMITTENT; CLOZAPINE; ANTIPSYCHOTICS; SCHIZOPHRENIA; HALOPERIDOL AB Background: Acute and long-term use of neuroleptics to treat bipolar disorder remains prevalent despite safety concerns. Neuroleptic-treated patients with bipolar disorder have been reported to have rates of tardive dyskinesia, akathisia, and acute dystonia as high as or higher than patients with schizophrenia. Moreover, the pattern of repeated, intermittent use of neuroleptics in bipolar disorder may increase rather than decrease the risk of tardive dyskinesia. Method: Retrospective life charts of 133 treatment-refractory patients with bipolar disorder (diagnosed according to Research Diagnostic Criteria or a clinical interview with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or the Structured Clinical Interview for DSM-IV Axis I Disorders) admitted to the National Institute of Mental Health (NIMH) were reviewed for prior neuroleptic use, medication exposure, and course of illness variables. Patients' medication response and degree of improvement while at NIMH were also assessed. Results: A total of 72.2% (N = 96) of the bipolar patients examined had exposure to neuroleptics prior to referral to NIMH. Neuroleptic-treated patients had a mean of 5.6 neuroleptic trials with a mean duration of 166.4 days for each trial and a dose range of 25 to 960 mg in chlorpromazine equivalents. Life chart data showed that the neuroleptic-exposed and nonexposed bipolar patients were distinguished by 1 course-of-illness variable: increased suicidality in the neuroleptic-treated group. Patients with and without prior neuroleptic exposure experienced the same high degree of improvement at discharge from NIMH. Only 12.5% (N = 12) of the group previously treated with typical neuroleptics (N = 96) required neuroleptics at discharge. Conclusion: Our data suggest that the majority of even treatment-refractory bipolar patients can be stabilized without neuroleptics. Given the high risk of tardive dyskinesia and the availability of other novel agents, the routine intermittent use of typical neuroleptics to treat patients with bipolar disorder should be minimized. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Fergus, EL (reprint author), NIMH, Biol Psychiat Branch, Bldg 10,Room 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. RI Brotman, Melissa/H-7409-2013 NR 51 TC 18 Z9 19 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 2000 VL 61 IS 1 BP 68 EP 74 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 285RY UT WOS:000085402900021 PM 10695653 ER PT J AU Ishai, A Ungerleider, LG Martin, A Haxby, JV AF Ishai, A Ungerleider, LG Martin, A Haxby, JV TI The representation of objects in the human occipital and temporal cortex SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; HUMAN VISUAL-CORTEX; AUTOMATED ALGORITHM; FACE RECOGNITION; NEURAL SYSTEMS; PERCEPTION; MECHANISMS; PROSOPAGNOSIA; ORGANIZATION; REGIONS AB Recently, we identified, using fMRI, three bilateral regions in the ventral temporal cortex that responded preferentially to faces, houses, and chairs [Ishai, A., Ungerleider, L. G., Martin, A., Schouten, J. L., & Haxby, J. V. (1999). Distributed representation of objects in the human ventral visual pathway. Proceedings of the National Academy of Sciences, U.S.A., 96, 9379-9384]. Here, we report differential patterns of activation, similar to those seen in the ventral temporal cortex, in bilateral regions of the ventral occipital cortex. We also found category-related responses in the dorsal occipital cortex and in the superior temporal sulcus. Moreover, rather chan activating discrete, segregated areas, each category was associated with its own differential pattern of response across a broad expanse of cortex. The distributed patterns of response were similar across tasks (passive viewing, delayed matching) and presentation formats (photographs, line drawings). We propose that the representation of objects in the ventral visual pathway, including both occipital and temporal regions, is not restricted to small, highly selective patches of cortex but, instead, is a distributed representation of information about object form. Within this distributed system, the representation of faces appears to be less extensive as compared to the representations of nonface objects. C1 NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Ishai, A (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C110, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 46 TC 201 Z9 205 U1 0 U2 10 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 VL 12 SU 2 BP 35 EP 51 DI 10.1162/089892900564055 PG 17 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 388QX UT WOS:000166194100005 PM 11506646 ER PT J AU Kastner, S AF Kastner, S TI Mechanisms of visual attention in the human cortex SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RI Winstein, Carolee/A-8375-2008 NR 0 TC 0 Z9 0 U1 1 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S BP 12 EP 12 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800013 ER PT J AU Reynolds, J AF Reynolds, J TI Competitive mechanisms of selective visual attention SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S BP 12 EP 12 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800012 ER PT J AU Weisberg, J van Turennout, M AF Weisberg, J van Turennout, M TI Effects of object form and task demands on repetition priming: An event-related fMRI study SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 59A BP 30 EP 30 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800088 ER PT J AU Corina, D San Jose, L Ackerman, D Guillemin, A Braun, A AF Corina, D San Jose, L Ackerman, D Guillemin, A Braun, A TI A comparison of neural systems underlying human action and American sign language processing: A PET study SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Univ Puerto Rico, Rio Piedras, PR 00931 USA. NIDCDS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 6B BP 43 EP 44 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800153 ER PT J AU Wharton, CM Thompson, J Sevostianov, A Graesser, AC Fromm, SJ Courtney, S Bowles, A Braun, AR AF Wharton, CM Thompson, J Sevostianov, A Graesser, AC Fromm, SJ Courtney, S Bowles, A Braun, AR TI The neural basis of language and situation models. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIDCD, NIH, Bethesda, MD USA. Univ Tennessee, Memphis, TN 38163 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 40B BP 50 EP 50 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800187 ER PT J AU Knutson, B Adams, S Kaiser, E Walker, J Hommer, D AF Knutson, B Adams, S Kaiser, E Walker, J Hommer, D TI FMRI visualization of brain activity during anticipation of monetary reward. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 74B BP 56 EP 56 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800221 ER PT J AU Ishai, A Haxby, JV Ungerleider, LG AF Ishai, A Haxby, JV Ungerleider, LG TI Distributed neural systems for the generation of visual images SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 23C BP 70 EP 70 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800285 ER PT J AU Chao, LL Martin, A AF Chao, LL Martin, A TI Memory in hand: Grasping the concept of tools SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI martin, alex/B-6176-2009 NR 0 TC 2 Z9 2 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 56C BP 76 EP 76 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800318 ER PT J AU Sevostianov, A Fromm, S Braun, A AF Sevostianov, A Fromm, S Braun, A TI Changes in fMRI signal support a right ear advantage in an auditory non-verbal dichotic attention task. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIDCD, NIH, Bethesda, MD USA. Inst Human Brain, St Petersburg, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 86C BP 81 EP 81 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800348 ER PT J AU Sirigu, A Giraux, P Zalla, T Basso, G Pietrini, P Grafman, J AF Sirigu, A Giraux, P Zalla, T Basso, G Pietrini, P Grafman, J TI Metabolic correlates of the perception of monetary gain and loss using fMRI. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Inst Cognit Sci, CNRS, Bron, France. NIH, Cognit Neurosci Sect, Bethesda, MD USA. RI Basso, Gianpaolo/A-9208-2012 OI Basso, Gianpaolo/0000-0002-6245-9402 NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 76D BP 100 EP 101 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800456 ER PT J AU Bokat, CE Elvevaag, B Goldberg, TE AF Bokat, CE Elvevaag, B Goldberg, TE TI Comparison of the semantic and lexical systems in schizophrenic patients and Alzheimer's disease patients SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, CBDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 79D BP 101 EP 101 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800459 ER PT J AU Gscheidle, TA Egan, MF Goldberg, TE Rawlins, R Bigelow, LB Weinberger, DR AF Gscheidle, TA Egan, MF Goldberg, TE Rawlins, R Bigelow, LB Weinberger, DR TI Cognitive dysfunction in siblings of patients with schizophrenia: Evidence for familiality SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 83D BP 102 EP 102 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800463 ER PT J AU Romero, SG Granetz, J Makale, M Manly, C Grafman, J AF Romero, SG Granetz, J Makale, M Manly, C Grafman, J TI Learning and memory in developmental dyscalculia SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 97D BP 104 EP 104 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800476 ER PT J AU Ernst, M Bolla, K Contoreggi, C Mouratidis, M Kurian, V Cadet, JL Kimes, A London, ED AF Ernst, M Bolla, K Contoreggi, C Mouratidis, M Kurian, V Cadet, JL Kimes, A London, ED TI Pattern of brain activation during a Gambling task. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 10E BP 109 EP 109 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800497 ER PT J AU San Jose, L Corina, D Ackerman, D Guillemin, A Braun, A AF San Jose, L Corina, D Ackerman, D Guillemin, A Braun, A TI H2O-15 positron emission tomography (PET) during American sign language (ASL) production in the deaf. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Puerto Rico, Rio Piedras, PR 00931 USA. Univ Washington, Seattle, WA 98195 USA. NIDCD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 63E BP 119 EP 119 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800550 ER PT J AU Xu, B Grafman, J Gaillard, WD Spanaki, M Ishii, K Balsamo, L Dunn, T Theodore, W AF Xu, B Grafman, J Gaillard, WD Spanaki, M Ishii, K Balsamo, L Dunn, T Theodore, W TI Activation during semantic and phonological processing: Cross-paradigm interference in functional imaging SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 113E BP 128 EP 128 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800598 ER PT J AU Anderson, KC Murray, EA Corkin, S Miller, EK AF Anderson, KC Murray, EA Corkin, S Miller, EK TI Conditional visuomotor learning in the amnesic patient HM SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. MIT, Ctr Learning & Memory, Cambridge, MA 02139 USA. MIT, RIKEN, Ctr Res Neurosci, Cambridge, MA 02139 USA. NIMH, Lab Neurospsychol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 28F BP 134 EP 134 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800630 ER PT J AU Jiang, Y Haxby, JV Martin, A Ungerleider, LG Parasuraman, R AF Jiang, Y Haxby, JV Martin, A Ungerleider, LG Parasuraman, R TI Complementary neural mechanisms for tracking items in human working memory SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2000 SU S MA 84F BP 144 EP 145 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 292UQ UT WOS:000085813800686 ER PT J AU Desper, R Jiang, F Kallioniemi, OP Moch, H Papadimitriou, CH Schaffer, AA AF Desper, R Jiang, F Kallioniemi, OP Moch, H Papadimitriou, CH Schaffer, AA TI Distance-based reconstruction of tree models for oncogenesis SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE cancer; algorithms; phylogenetic trees; comparative genomic hybridization ID RENAL-CELL CARCINOMA; COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; NUMERICAL TAXONOMY; CLONAL EVOLUTION; BREAST-CANCER; ABNORMALITIES; HETEROGENEITY; DELETIONS AB Comparative genomic hybridization (CGH) is a laboratory method to measure gains and losses in the copy number of chromosomal regions in tumor cells. It is hypothesized that certain DNA gains and losses are related to cancer progression and that the patterns of these changes are relevant to the clinical consequences of the cancer. It is therefore of interest to develop models which predict the occurrence of these events, as well as techniques for learning such models from CGH data. We continue our study of the mathematical foundations for inferring a model of tumor progression from a CGH data set that we started in Desper et al, (1999). In that paper, we proposed a class of probabilistic tree models and showed that an algorithm based on maximum-weight branching in a graph correctly infers the topology of the tree, under plausible assumptions. In this paper, we extend that work in the direction of the so-called distance-based trees, in which events are leaves of the tree, in the style of models common in phylogenetics, Then we show how to reconstruct the distance-based trees using tree-fitting algorithms developed by researchers in phylogenetics, The main advantages of the distance-based models are that 1) they represent information about co-occurrences of all pairs of events, instead of just some pairs, 2) they allow quantitative predictions about which events occur early in tumor progression, and 3) they bring into play the extensive methodology and software developed in the context of phylogenetics, We illustrate the distance-based tree method and how it complements the branching tree method, with a CGH data set for renal cancer. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Basel, Inst Pathol, Basel, Switzerland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. Deutsch Krebsforschungszentrum, Abt Theoret Bioinformat, D-6900 Heidelberg, Germany. RP Schaffer, AA (reprint author), NIH, Natl Ctr Biotechnol Informat, Bldg 38A,Room 8N 805,8600 Rockville Pike, Bethesda, MD 20894 USA. EM schaffer@helix.nih.gov RI Kallioniemi, Olli/H-5111-2011; Schaffer, Alejandro/F-2902-2012; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 36 TC 63 Z9 66 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 EI 1557-8666 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2000 VL 7 IS 6 BP 789 EP 803 DI 10.1089/10665270050514936 PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 421ET UT WOS:000168049700003 PM 11382362 ER PT J AU Byrant, P Gooch, B Backinger, C Lester, A Dornoto, P Capilouto, E White, BA AF Byrant, P Gooch, B Backinger, C Lester, A Dornoto, P Capilouto, E White, BA TI Expanding horizons, strengthening alliances to conduct practise-based and community-based research SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 CDC, Behav Sci Hlth Serv & Educ Res Grp, Atlanta, GA 30333 USA. NCI, Behav Sci Hlth Serv & Educ Res Grp, Bethesda, MD 20892 USA. Univ Washington, Behav Sci Hlth Serv & Educ Res Grp, Seattle, WA 98195 USA. Univ Alabama, Behav Sci Hlth Serv & Educ Res Grp, Birmingham, AL 35294 USA. Kaiser Permanente Ctr Hlth Res, Behav Sci Hlth Serv & Educ Res Grp, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1 BP 144 EP 144 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000002 ER PT J AU Antonucci, JM Stansbury, JW Fowler, BO AF Antonucci, JM Stansbury, JW Fowler, BO TI Synthesis and characterization of ethyl alpha-hydroxymethylacrylate, a novel isomeric analog of HEMA. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIST, Gaithersburg, MD 20899 USA. NIDCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 30 BP 147 EP 147 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000032 ER PT J AU Duthie, J Woodworth, W Knowler, W Pettitt, D Dunford, R Schlossman, M Carter, L AF Duthie, J Woodworth, W Knowler, W Pettitt, D Dunford, R Schlossman, M Carter, L TI Predictors of maxillary antral pseudocysts in a Pima Indian population SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 SUNY Buffalo, Sch Dent Med, Dept Oral Diagnost Sci, Buffalo, NY 14260 USA. SUNY Buffalo, Sch Dent Med, Dept Oral Biol, Buffalo, NY 14260 USA. NIDDK, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 176 BP 165 EP 165 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000176 ER PT J AU Moon, HS Jung, SH Horowitz, AM Paik, DI AF Moon, HS Jung, SH Horowitz, AM Paik, DI TI Public health center directors: Opinions about fluoridation. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. Seoul Natl Univ, Coll Dent, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 486 BP 204 EP 204 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000486 ER PT J AU Atkinson, JC Selwitz, RH Jones, GK Ragain, J Diamond, F AF Atkinson, JC Selwitz, RH Jones, GK Ragain, J Diamond, F TI BIS-DMA rapidly degrades in whole saliva. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, CRC, Bethesda, MD USA. NIDCR, HPADB, Bethesda, MD USA. NDRI, Great Lakes, IL USA. Natl Med Serv, Willow Grove, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 622 BP 221 EP 221 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000622 ER PT J AU Redmond, ND Kolenbrander, PE AF Redmond, ND Kolenbrander, PE TI Colonization of oral bacteria: Fluid mechanics of in vitro modeling SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 633 BP 223 EP 223 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000632 ER PT J AU Michalowicz, B Diehl, S Gunsolley, J Sparkes, B Brooks, C Koertge, T Califano, J Burmeister, J Schenkein, H AF Michalowicz, B Diehl, S Gunsolley, J Sparkes, B Brooks, C Koertge, T Califano, J Burmeister, J Schenkein, H TI Quantitative genetic studies of adult periodontitis in twins. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN USA. NIDCR, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 917 BP 258 EP 258 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000913 ER PT J AU Navazesh, M Mulligan, R Barron, Y Redford, M Greenspan, D Phelan, J AF Navazesh, M Mulligan, R Barron, Y Redford, M Greenspan, D Phelan, J TI Longitudinal evaluation of xerostomia and salivary gland hypofunction in HIV-women. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA 90089 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NIDCR, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. N Port V A LI, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 933 BP 260 EP 260 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937000929 ER PT J AU Roden, RD Thyagarajan, T Cho, A Sreenath, T Kulkarni, AB AF Roden, RD Thyagarajan, T Cho, A Sreenath, T Kulkarni, AB TI Linear analysis of murine craniofacial morphogenesis and tooth mineralization. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Alabama, Sch Dent, Birmingham, AL 35294 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1479 BP 328 EP 328 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001471 ER PT J AU Shum, L Nuckolls, GH Nonaka, K Dashner, R Slavkin, HC AF Shum, L Nuckolls, GH Nonaka, K Dashner, R Slavkin, HC TI Functional analysis of the Dach gene in tooth morphogenesis SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIAMSD, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1505 BP 332 EP 332 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001500 ER PT J AU Fedarko, NS Fohr, B Fisher, LW AF Fedarko, NS Fohr, B Fisher, LW TI DMP1 inactivates complement by bridging factor H to cell surface receptors. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1561 BP 339 EP 339 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001556 ER PT J AU Albander, JM Lamster, IB Adesanya, MR Diehl, SR Winn, D AF Albander, JM Lamster, IB Adesanya, MR Diehl, SR Winn, D TI Association between crevicular and serum IgG levels to P-gingivalis and early-onset periodontitis. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Bergen, Bergen, Norway. Columbia Univ, New York, NY USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1581 BP 341 EP 341 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001574 ER PT J AU Aframian, DJ Cukierman, E Nikolovski, J Zheng, C Goldsmith, C Mooney, DJ Yamada, KM Baum, BJ AF Aframian, DJ Cukierman, E Nikolovski, J Zheng, C Goldsmith, C Mooney, DJ Yamada, KM Baum, BJ TI Use of suicide gene in an allogeneic graft cell. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 1618 BP 346 EP 346 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937001616 ER PT J AU Albandar, JM Adesanya, MR Winn, DM AF Albandar, JM Adesanya, MR Winn, DM TI Cigars, pipes, and cigarettes as risk factors for periodontal disease. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Bergen, Bergen, Norway. NIDCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2047 BP 399 EP 399 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002038 ER PT J AU Cisar, JO Xu, DQ Thompson, J Swaim, W Hu, L Kopecko, D AF Cisar, JO Xu, DQ Thompson, J Swaim, W Hu, L Kopecko, D TI Absence of nanobacteria in human saliva and dental plaque. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2231 BP 422 EP 422 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002222 ER PT J AU Bartlett, JD Caterina, JJ Xue, J AF Bartlett, JD Caterina, JJ Xue, J TI Enamelysin (MMP-20) promoter characterization SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2241 BP 424 EP 424 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002235 ER PT J AU Reid, BC Winn, DM Garcia, AI Rozier, RG AF Reid, BC Winn, DM Garcia, AI Rozier, RG TI Comorbidity index development in a head and neck cancer population. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Connecticut, Farmington, CT USA. NIDCR, NIH, Bethesda, MD USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2519 BP 458 EP 458 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002510 ER PT J AU Gemmel, A Tavares, M Crawford, S Alperin, S Bellinger, D Soncini, J Braveman, N AF Gemmel, A Tavares, M Crawford, S Alperin, S Bellinger, D Soncini, J Braveman, N TI Serum lead levels and number of caries in the children's amalgam trial. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. Forsyth Inst, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2543 BP 461 EP 461 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002534 ER PT J AU Crawford, S Tavares, M Alpen, S Gemmel, A Soncini, J Braveman, N AF Crawford, S Tavares, M Alpen, S Gemmel, A Soncini, J Braveman, N TI Comparison of baseline variables for subjects in the children's amalgam trial. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. Forsyth Inst, Boston, MA USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2545 BP 462 EP 462 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002539 ER PT J AU Tavares, M Crawford, S Alperin, S Soncini, J Gemmell, A Braveman, N AF Tavares, M Crawford, S Alperin, S Soncini, J Gemmell, A Braveman, N TI Caries prevalence and treatment needs in the children's amalgam TnaI SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. New England Res Inst, Watertown, MA 02172 USA. NIDCR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2546 BP 462 EP 462 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002543 ER PT J AU Drury, TF Redford, M AF Drury, TF Redford, M TI Completing the clinical picture of America's adult oral health. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 2873 BP 503 EP 503 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937002867 ER PT J AU Woodworth, W Genco, RJ Knowler, W Pettitt, D Shlossman, M Dunford, R Duthie, J Carter, L AF Woodworth, W Genco, RJ Knowler, W Pettitt, D Shlossman, M Dunford, R Duthie, J Carter, L TI Calcified carotid atherosclerotic plaque as a predictor of CVD death. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDDKD, Phoenix, AZ USA. SUNY Buffalo, Buffalo, NY 14260 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3042 BP 524 EP 524 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003037 ER PT J AU Thyagarajan, TC Sreenath, T Cho, A Kulkarni, AB AF Thyagarajan, TC Sreenath, T Cho, A Kulkarni, AB TI Targeted over-expression of TGF-beta 1 in teeth results in dysplastic dentin. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, Funct Genom Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3057 BP 526 EP 526 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003049 ER PT J AU Ramirez, JL Brennan, MT Grisius, MM AF Ramirez, JL Brennan, MT Grisius, MM TI Salivary interleukin-4 in Primary Sjogren's Syndrome. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3072 BP 527 EP 527 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003064 ER PT J AU Khoo, LS Neloms, SM Goodman, HS Horowitz, AM AF Khoo, LS Neloms, SM Goodman, HS Horowitz, AM TI Epidemiology of oral cancer in Maryland. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Dept Hlth & Mental Hyg, Off Oral Hlth, Baltimore, MD USA. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3275 BP 553 EP 553 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003266 ER PT J AU Canto, MT Horowitz, AM Child, WL AF Canto, MT Horowitz, AM Child, WL TI Maryland physicians' views on oral cancer prevention and early detection. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIDCR, NIH, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3286 BP 554 EP 554 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003279 ER PT J AU Clovis, J Horowitz, AM Poel, DH AF Clovis, J Horowitz, AM Poel, DH TI British Columbia and Nova Scotia dental hygienists' knowledge of oral cancer. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Dalhousie Univ, Halifax, NS B3H 3J5, Canada. NIDR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3285 BP 554 EP 554 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003275 ER PT J AU Horowitz, AM Sheikh, A Siriphant, P Child, WL AF Horowitz, AM Sheikh, A Siriphant, P Child, WL TI Perspectives of Maryland dentists on oral cancer. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Chapel Hill, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3283 BP 554 EP 554 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003274 ER PT J AU Siriphant, P Horowitz, AM Child, WL AF Siriphant, P Horowitz, AM Child, WL TI Maryland nurse practitioners' perspectives on oral cancer SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3284 BP 554 EP 554 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003278 ER PT J AU Swango, P Kleinman, DV Drury, TF Horowitz, AM AF Swango, P Kleinman, DV Drury, TF Horowitz, AM TI Lifespan variations an oral musesal lesions among U.S adults. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethlehem, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3287 BP 554 EP 554 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003276 ER PT J AU Michalowicz, B Wu, T Best, A Schenkein, H Diehl, S AF Michalowicz, B Wu, T Best, A Schenkein, H Diehl, S TI Continuous measures of early-onset periodontitis for genetic research. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Minnesota, Minneapolis, MN USA. NIDCR, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3509 BP 582 EP 582 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003499 ER PT J AU Stevens, DR Cukierman, E Yamada, KM AF Stevens, DR Cukierman, E Yamada, KM TI Human fibroblast cell spreading in 3D extracellular matrix. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Creighton Univ, Sch Dent, Omaha, NE 68178 USA. NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3564 BP 589 EP 589 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003558 ER PT J AU Mulligan, R Navazesh, M Komaroff, E Greenspan, D Redford, M Phelan, J Alves, M AF Mulligan, R Navazesh, M Komaroff, E Greenspan, D Redford, M Phelan, J Alves, M TI Salivary gland disease indicators in HIV plus women from the WIHS. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA USA. NERI, Boston, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIDCR, Bethesda, MD USA. UIC, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3664 BP 601 EP 601 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003656 ER PT J AU Barros, S Chiariello, M Gutkind, S AF Barros, S Chiariello, M Gutkind, S TI Biological interaction between p73 and HPV E6 oncoprotein. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. Univ Campinas, Campinas, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3809 BP 620 EP 620 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003801 ER PT J AU Shi, S Mankani, M Albandar, JM Satomura, K Kuznetsov, S Robey, PG AF Shi, S Mankani, M Albandar, JM Satomura, K Kuznetsov, S Robey, PG TI Generating bent and fibrous tissues on the surfaces of human dentin and cementum by transplantation of human bone marrow stromal cells in vivo. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3821 BP 621 EP 621 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003811 ER PT J AU Young, MF Thyagarajan, T Aria, D Liang, J Chen, XD Sommer, B Mankani, M Xu, T AF Young, MF Thyagarajan, T Aria, D Liang, J Chen, XD Sommer, B Mankani, M Xu, T TI Biglycan and decorin are critical to craniofacial bone mass. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 2000 VL 79 SI SI MA 3822 BP 621 EP 621 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 277MH UT WOS:000084937003815 ER PT J AU Bailey, JJ Berson, AS Handelsman, H AF Bailey, JJ Berson, AS Handelsman, H TI Dysrhythmia hazard after hospitalization for myocardial infarction: Two ECG prognostic methods compared SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Conference of the International-Society-for-Computerized-Electrocardiology CY APR 29-MAY 04, 2000 CL YOSEMITE, CALIFORNIA SP Agilent Technologies Inc, GE Marquette Med Syst Inc, Medtron Physio Control Corp, Mortara Instrument Inc, Schillerag, Siemens Elema AB, Spacelabs Burdick Inc, Zymed Inc, NHLBI DE risk stratification; heart rate variability; signal-averaged electrocardiogram ID COST-EFFECTIVENESS; DEFIBRILLATOR; SURVIVORS; THERAPY; DEATH; RISK AB We retrieved reports of heart rate variability and signal-averaged electrocardiograms (SAECG) used to predict risk of a dysrhythmic event. From each report the number of cases with and without events was extracted to establish accurate values for true positive rate (tpr = sensitivity) and false positive rate (fpr = 1 minus specificity). For all the heart rate variability reports, these values were collected and tpr values were plotted versus fpr. The (fpr,tpr) data were summarized by a meta ROC graph using the method of Moses and Shapiro. A composite weighted mean value and 95% confidence interval were also derived. A summary meta-ROC curve for thc SAECG reports was similarly obtained., Meta-ROC analysis of multiple reports better summarizes the performances of different prognostic methods and allows the effect of combining tests for a larger population to be simulated. C1 NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NHLBI, Bioengn Sci Res Grp, Bethesda, MD 20892 USA. Agcy Healthcare Res & Qual, Ctr Practice & Technol Assessment, Rockville, MD USA. RP Bailey, JJ (reprint author), NIH, Ctr Informat Technol, Bldg 12A,Room 2007,MSC 5620, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 2000 VL 33 SU S BP 151 EP 154 DI 10.1054/jelc.2000.20294 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 404JV UT WOS:000167095000023 PM 11265715 ER PT J AU Dvorak, JA Kobayashi, S Abe, K Fujiwara, T Takeuchi, T Nagao, E AF Dvorak, JA Kobayashi, S Abe, K Fujiwara, T Takeuchi, T Nagao, E TI The application of the atomic force microscope to studies of medically important protozoan parasites SO JOURNAL OF ELECTRON MICROSCOPY LA English DT Article DE atomic force microscopy; contact mode; tapping mode; elasticity map imaging; phase imaging; parasitic protozoa; preparative protocols ID LIVING CELLS; SURFACE AB Both living and fixed specimens of the medically-important parasitic protozoa, Trypanosoma cruzi, Toxoplasma gondii, Giardia lamblia, Entamoeba histolytica, and Acanthamoeba spp. were studied by atomic force microscopy (AFM). The preparation of fixed specimens was similar to methods used for either scanning or transmission electron microscopy. AFM scanning was performed using both contact and tapping modes. A classical fixation procedure utilizing glutaraldehyde followed by ethanol dehydration was not suitable for all parasite species. AFM images could not be obtained from fixed samples of T. cruzi, T. gondii or E. histolytica. However, excellent topographic images could be obtained from specimens of G. lamblia and Acanthamoeba under identical conditions. Critical point drying permitted AFM imaging of both trypomastigote and epimastigote stages of T. cruzi. Phase imaging of T. cruzi elucidated unique surface details at a level of resolution not visible using any other imaging modalities. AFM elasticity map imaging of ir: cruzi-infected and T. gondii-infected cells demonstrated that both parasites were markedly firmer than the surrounding host cell cytoplasm. The parasitophorous vacuole surrounding replicating T. gondii tachyzoites was also visualized by elasticity map imaging. These data suggest that although much remains to be learned about preparing parasitic protozoa for AFM imaging, the technique has the potential of providing unique and important insights into these disease causing organisms. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Keio Univ, Sch Med, Dept Trop Med & Parasitol, Shinjuku Ku, Tokyo 1608582, Japan. Hokkaido Univ, Grad Sch Med, Dept Anat, Kita Ku, Sapporo, Hokkaido 0608638, Japan. Keio Univ, Sch Med, Electron Microscopy Lab, Shinjuku Ku, Tokyo 1608582, Japan. RP Dvorak, JA (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room B2-11, Bethesda, MD 20892 USA. RI Kobayashi, seiki/L-4026-2013 NR 28 TC 13 Z9 14 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-0744 J9 J ELECTRON MICROSC JI J. Electron Microsc. PY 2000 VL 49 IS 3 BP 429 EP 435 PG 7 WC Microscopy SC Microscopy GA 336NA UT WOS:000088308100006 PM 11108031 ER PT J AU Nagao, E Nishijima, H Akita, S Nakayama, Y Dvorak, JA AF Nagao, E Nishijima, H Akita, S Nakayama, Y Dvorak, JA TI The cell biological application of carbon nanotube probes for atomic force microscopy: comparative studies of malaria-infected erythrocytes SO JOURNAL OF ELECTRON MICROSCOPY LA English DT Article DE atomic force microscopy; malaria; nanotube probe; erythrocyte; Plasmodium falciparum; knobs ID TIPS AB We describe the first cell. biological application of carbon nanotube (CN) probes for atomic force microscopy studies. Topographic and phase images were collected from Plasmodium falciparum malaria-infected erythrocytes using both TappingMode Etched Silicon Probes (TESP probe) and CN probes. We estimate that the lateral resolution of a CN probe-generated topographic image is at least four-fold higher than that of the TESP probe. Carbon nanotube probe-generated phase images of P. falciparum-induced knobs on the surface of erythrocytes also show a markedly higher lateral resolution than comparable TESP probe-generate phase images of the same area. We conclude that CN probes are useful for cell biological atomic force microscopy studies and should play an increasingly important role in the future of this evolving discipline. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Osaka Prefecture, Dept Phys & Elect, Osaka 5998531, Japan. RP Dvorak, JA (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA. RI akita, seiji/G-4679-2012 OI akita, seiji/0000-0002-2116-4034 NR 12 TC 18 Z9 21 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-0744 J9 J ELECTRON MICROSC JI J. Electron Microsc. PY 2000 VL 49 IS 3 BP 453 EP 458 PG 6 WC Microscopy SC Microscopy GA 336NA UT WOS:000088308100009 PM 11108034 ER PT J AU Chen, JT Hortin, GL AF Chen, JT Hortin, GL TI Interferences with semen detection by an immunoassay for a seminal vesicle-specific antigen SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; semen; identification; seminal vesicles; immunoassay seminal vesicle specific antigen ID MONOCLONAL-ANTIBODY; IDENTIFICATION; ELISA AB A commercial enzyme-linked immunosorbent assay (ELISA), the SEMA(R) assay, for a seminal vesicle-specific antigen (SVSA) provides highly sensitive detection of semen. Here we show marked interference of proteins such as albumin, serum proteins, or mucin with the assay. This would substantially decrease the sensitivity for detecting semen mixed with other biological fluids such as blood or vaginal secretions. C1 NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Clin Pathol, Bldg 10,Room 2C-407,10 Ctr Dr, Bethesda, MD 20892 USA. NR 8 TC 4 Z9 5 U1 0 U2 2 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD JAN PY 2000 VL 45 IS 1 BP 234 EP 235 PG 2 WC Medicine, Legal SC Legal Medicine GA 293BB UT WOS:000085830700039 PM 10641949 ER PT J AU Li-Smerin, YY Hackos, DH Swartz, KJ AF Li-Smerin, YY Hackos, DH Swartz, KJ TI alpha-helical structural elements within the voltage-sensing domains of a K+ channel SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE secondary structure; scanning mutagenesis; amphipathic; Fourier transform; voltage-dependent gating ID SHAKER POTASSIUM CHANNEL; TRANSMEMBRANE SEGMENTS; MOLECULAR-BASIS; S4 SEGMENT; ELECTROSTATIC INTERACTIONS; PHOSPHOLIPID-MEMBRANES; SUBUNIT STOICHIOMETRY; GATING MODIFIER; SODIUM-CHANNEL; TEA BLOCKADE AB Voltage-gated K+ channels are tetramers with each subunit containing six (S1-S6) putative membrane spanning segments. The fifth through sixth transmembrane segments (S5-S6) from each of four subunits assemble to form a central pore domain. A growing body of evidence suggests that the first four segments (S1-S4) comprise a domain-like voltage-sensing structure. While the topology of this region is reasonably well defined, the secondary and tertiary structures of these transmembrane segments are not. To explore the secondary structure of the voltage-sensing domains, we used alanine-scanning mutagenesis through the region encompassing the first four transmembrane segments in the drk1 voltage-gated K+ channel. We examined the mutation-induced perturbation in gating free energy for periodicity characteristic of alpha-helices. Our results are consistent with at least portions of S1, S2, S3, and S4 adopting alpha-helical secondary structure. In addition, both the S1-S2 and S3-S4 linkers exhibited substantial helical character: The distribution of gating perturbations for S1 and S2 suggest that these two helices inter-act primarily with two environments. In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain. C1 NINDS, Mol Physiol & Biophys Unit, NIH, Bethesda, MD 20892 USA. RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Unit, NIH, Bldg 36 Room 2C19,36 Convent Dr,MSC 4066, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA NS002945-13] NR 54 TC 138 Z9 141 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JAN PY 2000 VL 115 IS 1 BP 33 EP 49 PG 17 WC Physiology SC Physiology GA 273GA UT WOS:000084698500005 PM 10613917 ER PT J AU Kim, JM Hong, Y Jeang, KT Kim, S AF Kim, JM Hong, Y Jeang, KT Kim, S TI Transactivation activity of the human cytomegalovirus IE2 protein occurs at steps subsequent to TATA box-binding protein recruitment SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID RNA-POLYMERASE-II; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTIONAL ACTIVATION DOMAINS; IMMEDIATE-EARLY PROTEINS; SV40 EARLY PROMOTER; NF-KAPPA-B; IN-VIVO; TERMINAL DOMAIN; FACTOR TFIIB; TYPE-1 TAT AB The IE2 protein of human cytomegalovirus transactivates viral and cellular promoters through a wide variety of cis-elements, but the mechanism of its action has not been well characterized. Here, IE2-Sp1 synergy and IE2-TATA box-binding protein (TBP) interaction are examined by artificial recruitment of either Sp1 or TBP to the promoter. It was found that IE2 could cooperate with DNA-bound Sp1.A 117 amino acid glutamine-rich fragment of Sp1, which can interact with Drosophila TAF(II)110 and human TAF(II)130, was sufficient for the augmentation of IE2-driven transactivation. In binding assays in vitro, IE2 interacted directly with the C-terminal region of Sp1,which contains the zinc finger DNA-binding domain, but not with its transactivation domain, suggesting that synergy between IE2 and the transactivation domain of Sp1 might be mediated by other proteins such as TAF or TBP. It was also found that TBP recruitment to the promoter markedly increased IE2-mediated transactivation. Thus, IE2 acts synergistically with DNA-bound Sp1 and DNA-bound TBP. These results suggest that, in human cytomegalovirus IE2 transactivation, Sp1 functions at an early step such as recruitment of TBP and IE2 acts to accelerate rate-limiting steps after TBP recruitment. C1 Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. NIAID, Bethesda, MD 20892 USA. RP Kim, S (reprint author), Seoul Natl Univ, Inst Mol Biol & Genet, Bldg 105, Seoul 151742, South Korea. RI Jeang, Kuan-Teh/A-2424-2008 NR 55 TC 11 Z9 12 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JAN PY 2000 VL 81 BP 37 EP 46 PN 1 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 272CG UT WOS:000084632500004 PM 10640540 ER PT J AU Tamura, K Jones, M Yamada, I Ferrans, VJ AF Tamura, K Jones, M Yamada, I Ferrans, VJ TI Wound healing in the mitral valve SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID COLLAGEN-SYNTHESIS; CELLS; ANGIOGENESIS; PROSTHESES; REPAIR; INVIVO AB Background and aims of the study: Limited information is available on the healing of wounds in the mitral valve. In the present study, this process has been evaluated in young sheep. Methods: Histologic, histochemical and transmission electron microscopic studies were made of the healing of wounds produced surgically under cardiopulmonary bypass, in the mitral valve (a 1 cm-long radially oriented incision at the free edge of the anterior leaflet) of young sheep (n = 11). Results: All animals developed severe mitral regurgitation, as demonstrated by hemodynamic, ultrasound and ventriculographic studies. At four to five weeks, the edges of the incision were only partially covered by endothelium and had small deposits of fibrin. Two types of granulation tissue were associated with wound healing. The first covered the cut edge and consisted of myxoid tissue that extended from the valvular spongiosa and fibrosa; the second type consisted of spindle-shaped cells arranged parallel to the surface and surrounded by a slightly myxoid stroma. This granulation tissue resembled that caused by reactive fibrosis in regurgitant mitral valves. The connective tissue cells in granulation tissue developed increasing amounts of actin-like filaments as a function of time after operation. This differentiation resulted in the development of myofibroblasts. In contrast to the avascular nature of normal mitral leaflets, capillaries and arterioles first appeared in the middle portion of the leaflet at eight weeks, and at the proximal edges of the wounds at 12 weeks. Conclusion: The healing of mitral valvular wounds is a slow process that requires between eight and 12 weeks for the formation of a dense collagenous scar at the edges and complete restoration of the endothelial lining. Progression of healing is associated with the phenotypic modulation of connective tissue cells from fibroblasts to myofibroblasts and neovascularization of the leaflets. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA. RP Tamura, K (reprint author), Nippon Med Sch, Dept Pathol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138602, Japan. NR 22 TC 27 Z9 28 U1 0 U2 1 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD, ENGLAND HA6 2ET SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD JAN PY 2000 VL 9 IS 1 BP 53 EP 63 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 276YH UT WOS:000084905600011 PM 10678376 ER PT J AU Romeo, R Hegerich, P Emerson, SU Colombo, M Purcell, RH Bukh, J AF Romeo, R Hegerich, P Emerson, SU Colombo, M Purcell, RH Bukh, J TI High prevalence of TT virus (TTV) infection in naive chimpanzees and in HCV positive humans. Identification of new TTV genotypes in chimpanzees SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract C1 Univ Milan, Dept Internal Med, I-20122 Milan, Italy. NIH, Hepatitis Viruses Sect, Bethesda, MD 20892 USA. NIH, Mol Hepatitis Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2000 VL 32 SU 2 BP 90 EP 90 DI 10.1016/S0168-8278(00)80677-7 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 315GP UT WOS:000087104500249 ER PT J AU Lopex-Labrador, FX He, XS Berenguer, M Lu, Y Boisvert, J Cheung, R Rehermann, B Davis, MM Wright, T Greenberg, HB AF Lopex-Labrador, FX He, XS Berenguer, M Lu, Y Boisvert, J Cheung, R Rehermann, B Davis, MM Wright, T Greenberg, HB TI Visualisation of hepatitis C virus-specific cytotoxic T cells using peptide-MHC tetramers: Variations in the viral epitope and relationship with the viral load SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract C1 VAMC, Palo Alto, CA USA. Stanford Univ, San Francisco, CA USA. NIDDK, NIH, Bethesda, MD USA. Univ Calif San Francisco, VAMC, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PY 2000 VL 32 SU 2 BP 172 EP 172 DI 10.1016/S0168-8278(00)80983-6 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 315GP UT WOS:000087104500555 ER PT J AU Fan, Y Hwang, K Gill, M Huang, HK AF Fan, Y Hwang, K Gill, M Huang, HK TI Some connectivity and security issues of NGI in medical imaging applications SO JOURNAL OF HIGH SPEED NETWORKS LA English DT Article DE Internet; Internet2; Next Generation Internet (NGI); medical imaging; telemedicine; teleradiology; data security AB The next generation internet (NGI) or Internet2 is an initiative for the integration of higher speed backbone communication networks as a means to replace the current inadequate Internet for many applications including medical imaging. This paper first reviews the current status of the Internet2 and reasons why telemedicine and teleradiology require its service. A case study is given using the private ATM OC-3 network at the Laboratory for Radiological Informatics, UCSF as an example for connecting a local site to the Internet2. Network security and data integrity are discussed in both the global and the local network level. Some preliminary results on Internet2 performance in the regional and the national level, as well as comparing with other WAN technologies are given. C1 Univ Calif San Francisco, Lab Radiol Informat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Enterprise Network Serv, San Francisco, CA 94134 USA. Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Fan, Y (reprint author), Univ So Calif, Childrens Hosp Los Angeles, Dept Radiol, Mailstop 81,4650 Sunset Blvd, Los Angeles, CA 90027 USA. NR 10 TC 9 Z9 9 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-6801 J9 J HIGH SPEED NETW JI J. High Speed Netw. PY 2000 VL 9 IS 1 BP 3 EP 13 PG 11 WC Computer Science, Information Systems SC Computer Science GA 340NT UT WOS:000088541400002 ER PT J AU Lan, JC Chen, Q Wu, DL Ding, H Pong, DB Zhao, TM AF Lan, JC Chen, Q Wu, DL Ding, H Pong, DB Zhao, TM TI Genetic polymorphism of RhD-negative associated haplotypes in the Chinese SO JOURNAL OF HUMAN GENETICS LA English DT Article DE molecular basis of Rh blood group; novel RhD-negative haplotypes; Chinese population ID MOLECULAR-CLONING; BLOOD; POLYPEPTIDE; PATIENT; DONORS; DNA AB The Rh blood group is the most polymorphic human blood group system, and is clinically significant in transfusion medicine: Individuals are classified as Rh-positive and Rh-negative depending on the presence or absence of the D antigen on the red cell surface. The RhD-negative trait could be generated by multiple genetic mechanisms, which have been shown to be ethnic group-dependent. In this study. we evaluated the status of seven RND-specific exons (exons 3, 4, 5, 6, 7, 9, and 10) and RH intron 4 in 119 Chinese blood donors, using the sequence-specific primers polymerase chain reaction (SSP-PCR). Of the 87 individuals who were RhD-negative, 52 with the ce ce, ce/cE, or Ce/ce genotype (60%) lacked the above seven RHD exons, 22 with the Ce/Ce or Ce/ce genotype (25%) had all the RHD exons examined; 13 with the Ce/ce genotype (15%) carried at least one RHD exon. Antigen association analysis suggested the existence of a novel class of RhD-negative associated haplotypes in the Chinese, tentatively denoted D(nf)Ce. The D(nf)Ce haplotype consisted of a normal RHCe allele and a nonfunctional RHD gene, which vary depending on the structure of the RHD gene. Among the RhD-negative Chinese, the estimated frequencies of the dce, dCe, and D(nf)Ce haplotypes were 0.7500, 0.0465. and 0.2035, respectively. No statistically significant deviation from Hardy-Weinberg equilibrium was observed using this genetic model. C1 NIAID, Mol & Cellular Immunogenet Sect, NIH, Bethesda, MD 20892 USA. Nanfang Hosp, Blood Bank, Guangzhou, Peoples R China. Inst Blood Transfus, Chengdu, Peoples R China. RP Zhao, TM (reprint author), NIAID, Mol & Cellular Immunogenet Sect, NIH, Bldg 9,Room 1S111,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 20 Z9 48 U1 1 U2 1 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113, JAPAN SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PY 2000 VL 45 IS 4 BP 224 EP 227 DI 10.1007/s100380050006 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 334ZL UT WOS:000088216700006 PM 10944852 ER PT J AU Yang, QF Sakurai, T Shan, L Yu, ZG Yoshimura, G Suzuma, T Tamaki, T Umemura, T Nakamura, M Nakamura, Y Mori, I Kakudo, K AF Yang, QF Sakurai, T Shan, L Yu, ZG Yoshimura, G Suzuma, T Tamaki, T Umemura, T Nakamura, M Nakamura, Y Mori, I Kakudo, K TI Novel polymorphisms of prostate-specific antigen (PSA) gene associated with PSA mRNA expression in breast cancer SO JOURNAL OF HUMAN GENETICS LA English DT Article DE prostate-specific antigen gene; polymorphism; promoter; breast cancer; Japanese; genotyping ID HORMONE-RELATED PROTEIN; MESSENGER-RNA; WOMEN AB A growing body of evidence suggests that prostate-specific antigen (PSA) is a novel prognostic factor for breast cancer. The molecular mechanism of variant PSA expression in breast cancer has remained poorly understood in spite of intensive research. Previous studies have shown that the coding region of the PSA gene is not a target for mutations in prostate: cancer and breast cancer. The purpose of this: study was to analyze genetic variations in the promoter region of the PSA gene, and to detect whether such variations are correlated with PSA mRNA expression in breast tumors. We identified two polymorphisms in the proximal promoter legion of the PSA gene. These polymorphisms al-e located at positions -252 (G or A) and -205 (A or AA), and generate three genotypes. The genotypes were associated with PSA mRNA expression. Our findings suggest that these polymorphisms identified in the proximal promoter region may affect the transcriptional activity of PSA. C1 Wakayama Med Coll, Dept Pathol 2, Wakayama 6410012, Japan. Wakayama Med Coll, Affiliated Kihoku Hosp, Dept Surg, Wakayama 6410012, Japan. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Yang, QF (reprint author), Wakayama Med Coll, Dept Pathol 2, 811-1 Kimiidera, Wakayama 6410012, Japan. RI Nakamura, Yasushi/J-5143-2014 NR 21 TC 12 Z9 14 U1 0 U2 1 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113, JAPAN SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PY 2000 VL 45 IS 6 BP 363 EP 366 DI 10.1007/s100380070009 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 376TE UT WOS:000165472200009 PM 11185746 ER PT J AU Luoto, R Sharrett, AR Schreiner, P Sorlie, PD Arnett, D Ephross, S AF Luoto, R Sharrett, AR Schreiner, P Sorlie, PD Arnett, D Ephross, S TI Blood pressure and menopausal transition: the Atherosclerosis Risk in Communities study (1987-95) SO JOURNAL OF HYPERTENSION LA English DT Article DE menopause; blood pressure; hypertension; weight change; ethnicity ID HEART-DISEASE; WOMEN; HYSTERECTOMY; FRAMINGHAM; POPULATION; WEIGHT; AGE AB Objective Blood pressure changes during menopausal transition have not been studied previously using a biracial sample. We invesigated whether menopausal transition was associated with change in blood pressure in African-American or white women. Design, setting and participants The prospective multicenter study, the Atherosclerosis Risk In Communities (ARIC) Study (1987-95) was utilized. Included were never-users of hormone replacement therapy (3800 women, 44% of the original sample). Main outcome measure Changes in blood pressure were adjusted for baseline age and body mass index, baseline blood pressure, antihypertensive use, ARIC field center and weight change. The menopausal transition group was compared to the non-transition group, separately, by ethnicity, Results Women undergoing the menopausal transition did not differ significantly in regard to systolic blood pressure change [5.2, 95% confidence interval (CI) 4.0- 6.4] from non-transitional women (4.6, 95% CI 4.0-5.2); adjustment for age, baseline systolic blood pressure and other factors did not alter this finding. Transitional women had significantly less diastolic blood pressure change (-0.5, 95% CI -1.1 to 0.2) than non-transitional women (-2.0, 95% CI -2.4 to -1.7, P = 0.000) but, after adjustment for other covariates, the result was not significant. African-American women had significantly (P = 0.003) higher systolic blood pressure change compared to white women, but this difference became non-significant (P = 0.21) after restricting the sample to women younger than 55 years of age. Interactions between menopausal transition and ethnicity were not significant, either in systolic blood pressure or diastolic blood pressure change. Conclusion Menopausal transition is not associated with significant blood pressure change in African-American or white women. J Hypertens 2000, 18:27-33 (C) Lippincott Williams & Wilkins. C1 Natl Publ Hlth Inst, Dept Hlth & Disabil, FIN-00300 Helsinki, Finland. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Glaxo Wellcome Inc, Worldwide Epidemiol, Res Triangle Pk, NC 27709 USA. RP Luoto, R (reprint author), Natl Publ Hlth Inst, Dept Hlth & Disabil, Mannerheimintie 166, FIN-00300 Helsinki, Finland. NR 20 TC 23 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JAN PY 2000 VL 18 IS 1 BP 27 EP 33 DI 10.1097/00004872-200018010-00005 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 278VK UT WOS:000085009500005 PM 10678540 ER PT J AU Adams, D van der Weyden, L Rasko, J Copeland, N Ioannou, P Morris, B AF Adams, D van der Weyden, L Rasko, J Copeland, N Ioannou, P Morris, B TI RNA binding protein control of renin expression SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract C1 Univ Sydney, Sydney, NSW 2006, Australia. Centennary Inst, Sydney, NSW, Australia. NCI, Frederick, MD 21701 USA. Murdoch Inst, Melbourne, Vic, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PY 2000 VL 18 SU 4 BP S3 EP S3 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 366HW UT WOS:000090000800011 ER PT J AU Bagrov, A Lopatin, D Lakatta, E Fedorova, O AF Bagrov, A Lopatin, D Lakatta, E Fedorova, O TI Phosphorylation of the sodium pump - a mechanism for interaction of endogenous Na,K-ATPase ligands and other vasoreactive hormones SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract C1 NIA, NIH, Cardiovasc Sci Lab, Baltimore, MD USA. Ott Inst Obstet & Gynecol, St Petersburg, Russia. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PY 2000 VL 18 SU 4 BP S244 EP S245 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 366HW UT WOS:000090000801349 ER PT J AU Fedorova, O Talan, M Agalakova, N Kolodkin, N Howald, W Lakatta, E Bagrov, A AF Fedorova, O Talan, M Agalakova, N Kolodkin, N Howald, W Lakatta, E Bagrov, A TI An endogenous ligand of alpha-1, Na,K-ATPase in Dahl hypertension SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Verta Peptides Inc, St Petersburg, Russia. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PY 2000 VL 18 SU 4 BP S72 EP S72 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 366HW UT WOS:000090000800378 ER PT J AU Lenders, J Pacak, K Friberg, P Walther, M Keiser, H Eisenhofer, G AF Lenders, J Pacak, K Friberg, P Walther, M Keiser, H Eisenhofer, G TI Plasma free metanephrines: A promising new neurochemical test for pheochromocytoma SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract C1 UMC St Radboud, Dept Internal Med, Nijmegen, Netherlands. Univ Gothenburg, Dept Clin Physiol, Gothenburg, Sweden. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. NIC, Urol Oncol Branch, NIH, Bethesda, MD USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neurocardiol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PY 2000 VL 18 SU 4 BP S34 EP S34 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 366HW UT WOS:000090000800169 ER PT J AU Chang, JT Segal, BM Shevach, EM AF Chang, JT Segal, BM Shevach, EM TI Role of costimulation in the induction of the IL-12/PL-12 receptor pathway and the development of autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CD40 LIGAND EXPRESSION; T-CELLS; CLONAL EXPANSION; IL-2 RECEPTOR; B-CELLS; TH2; CTLA-4; CD28; RESPONSES AB Costimulation mediated by the interactions of the B7 Ags (CD80/CD86) on APC with CD28 on the responding T cell regulates the magnitude of the immune response and may influence Th1/Th2 development. The IL-12R beta 2 subunit plays a critical role in maintaining IL-12 responsiveness and controlling Th1 lineage commitment. We demonstrate that IL-2 and IL-12 resulting from CD28/B7 interactions both play a critical role in the induction of expression of the IL-12R beta 2 subunit and as a result the differentiation of pathogenic autoreactive effector cells. These findings suggest that targeting IL-2 and IL-12 simultaneously may be effective in the treatment of Th1-mediated autoimmunity. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 41 TC 40 Z9 40 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 100 EP 106 PG 7 WC Immunology SC Immunology GA 266VP UT WOS:000084321200017 PM 10604999 ER PT J AU Thornton, AM Shevach, EM AF Thornton, AM Shevach, EM TI Suppressor effector function of CD4(+)CD25(+) immunoregulatory T cells is antigen nonspecific SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR TRANSGENIC MICE; IN-VITRO; AUTOIMMUNE-DISEASES; SELF-TOLERANCE; BASIC-PROTEIN; SUBSET; GENERATION; CONTAINS; THYMUS AB CD4(+)CD25(+) T cells represent a unique population of "professional" suppressor T cells that prevent induction of organ-specific autoimmune disease. In vitro, CD4(+)CD25(+) cells were anergic to simulation via the TCR and when cultured with CD4(+)CD25(-) cells, markedly suppressed polyclonal T cell proliferation by specifically inhibiting the production of IL-2, Suppression was cytokine independent, cell contact dependent, and required activation of the suppressors via their TCR, Further characterization of the CD4(+)CD25(+) population demonstrated that they do not contain memory or activated T cells and that they act through an APC-independent mechanism. CD4(+)CD25(+) T cells isolated from TCR transgenic (Tg) mice inhibited responses of CD4(+)CD25(-) Tg T cells to the same Ag, but also inhibited the Ag-specific responses of Tg cells specific for a distinct Ag, Suppression required that both peptide/MHC complexes be present in the same culture, but the Ags could be presented by two distinct populations of APC,When CD4(+)CD25(+) T cells were cultured with anti-CD3 and IL-2, they expanded, remained anergic, and in the absence of restimulation via their TCR, suppressed Ag-specific responses of CD4(+)CD25(-) T cells from multiple TCR transgenics, Collectively, these data demonstrate that CD4(+)CD25(+) T cells require activation via their TCR to become suppressive, but once activated, their suppressor effector function is completely nonspecific, The cell surface molecules involved in this T-T interaction remain to be characterized. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. NR 31 TC 893 Z9 936 U1 2 U2 16 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 183 EP 190 PG 8 WC Immunology SC Immunology GA 266VP UT WOS:000084321200028 PM 10605010 ER PT J AU Lee, JK Sayers, TJ Brooks, AD Back, TC Young, HA Komschlies, KL Wigginton, JM Wiltrout, RH AF Lee, JK Sayers, TJ Brooks, AD Back, TC Young, HA Komschlies, KL Wigginton, JM Wiltrout, RH TI IFN-gamma-dependent delay of in vivo tumor progression by Fas overexpression on murine renal cancer cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE-TRANSFER; DEATH FACTOR; LIGAND; EXPRESSION; APOPTOSIS; ANTIGEN; REGRESSION; MODULATION; CYTOKINES; INDUCTION AB The role of Fas in the regulation of solid tumor growth was investigated. Murine renal carcinoma (Renca) cells were constitutively resistant to Fas-mediatcd killing in vitro, but exhibited increased expression of Fas and sensitivity to Fas-mediated killing after exposure to IFN-gamma and TNF. Transfected Renca cells overexpressing Fas were efficiently killed in vitro upon exposure to anti-Fas Ab (Jo2). When Fas-overexpressing Renca cells were injected into syngenic BALB/c mice, there was a consistent and significant delay in tumor progression, reduced metastasis, and prolonged survival that was not observed for Renca cells that overexpressed a truncated nonfunctional Fas receptor. The delay of in vivo tumor growth induced by Fas overexpression was not observed in IFN-gamma(-/-) mice, indicating that IFN-gamma is required for the delay of in vivo tumor growth, However, there was a significant increase of infiltrated T cells and in vivo apoptosis in Fas-overexpressing Renca tumors, and Fas-overexpressing Renca cells were also efficiently killed in vitro by T cells. In addition, a strong therapeutic effect was observed on Pas-overexpressing tumor cells by in vivo administration of anti-Fas Abl confirming that overexpressed Fas provides a functional target in vivo for Fas-specific ligands, Therefore, our findings demonstrate that Fas overexpression on solid tumor cells can delay tumor growth and provides a rationale for therapeutic manipulation of Fas expression as a means of inducing tumor regression in vivo. C1 NCI, Expt Therapeut Sect, Expt Immunol Lab, Div Basic Sci,Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. NCI, Pediat Oncol Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Wiltrout, RH (reprint author), NCI, Expt Therapeut Sect, Expt Immunol Lab, Div Basic Sci,Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-93, Ft Detrick, MD 21702 USA. RI Sayers, Thomas/G-4859-2015 FU NCI NIH HHS [N01-CO-56000] NR 30 TC 58 Z9 61 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 JAN 1 PY 2000 VL 164 IS 1 BP 231 EP 239 PG 9 WC Immunology SC Immunology GA 266VP UT WOS:000084321200034 PM 10605016 ER PT J AU Dzuris, JL Sidney, J Appella, E Chesnut, RW Watkins, DI Sette, A AF Dzuris, JL Sidney, J Appella, E Chesnut, RW Watkins, DI Sette, A TI Conserved MHC class I peptide binding motif between humans and rhesus macaques SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; T-CELL EPITOPES; ENDOGENOUS PEPTIDES; ANCHOR RESIDUES; LYMPHOCYTES-T; HEPATITIS-E; ANTIGEN; MOLECULES; MONKEYS; DEFINITION AB Since the onset of the HIV pandemic, the use of nonhuman primate models of infection has increasingly become important. An excellent model to study HIV infection and immunological responses, in particular cell-mediated immune responses, is SIV infection of rhesus macaques, CTL epitopes have been mapped using SIV-infected rhesus macaques, but, to date, a peptide binding moth has been described for only one rhesus class I MHC molecule, Mamu-A*01. Herein, we have established peptide-live cell binding assays for four rhesus MNC class I molecules: Mamu-A*11, -B*03, -B*04, and -B*17. Using such assays, peptide binding motifs have been established for all four of these rhesus MHC class I molecules. With respect to the nature and spacing of crucial anchor positions, the motifs defined for Mamu-B*04 and -B*17 present unique features not previously observed for other primate species, The motifs identified for Mamu-A*11 and -B*03 are very similar to the peptide binding moths previously described for human HLA-B*44 and -B*27, respectively, Accordingly, naturally processed peptides derived from HLA-B*44 and HLA-B*27 specifically hind Mamu-A*11 and Mamu-B*03, respectively, indicating that conserved MHC class I binding capabilities exist between rhesus macaques and humans. The definition of four rhesus MHC class I-specific moths expands our ability to accurately detect and quantitate immune responses to MHC class I-restricted epitopes in rhesus macaques and to rationally design peptide epitope-based model vaccine constructs destined for use in nonhuman primates. C1 Epimmune, San Diego, CA 92121 USA. NIH, NCI, Bethesda, MD 20892 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. RP Dzuris, JL (reprint author), Epimmune, 5820 Nancy Ridge Dr, San Diego, CA 92121 USA. OI Dzuris, John/0000-0002-0046-8426 FU NIAID NIH HHS [2 R44 AI38081]; PHS HHS [R01 A14193, N01-A1-45241] NR 57 TC 47 Z9 49 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 283 EP 291 PG 9 WC Immunology SC Immunology GA 266VP UT WOS:000084321200040 PM 10605022 ER PT J AU Korthauer, U Nagel, W Davis, EM Le Beau, MM Menon, RS Mitchell, EO Kozak, CA Kolanus, W Bluestone, JA AF Korthauer, U Nagel, W Davis, EM Le Beau, MM Menon, RS Mitchell, EO Kozak, CA Kolanus, W Bluestone, JA TI Anergic T lymphocytes selectively express an integrin regulatory protein of the cytohesin family SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GUANINE-NUCLEOTIDE-EXCHANGE; ADP-RIBOSYLATION FACTOR; CELL CLONAL ANERGY; ANTIGEN RECEPTOR; PERIPHERAL TOLERANCE; TRANSGENIC MICE; IL-2 GENE; MONOCLONAL-ANTIBODIES; EXTRATHYMIC TOLERANCE; SIGNALING PATHWAY AB It has been proposed that the maintenance of T cell anergy depends on the induction of negative regulatory factors. Differential display of reverse transcribed RNA was used to identify novel genes that might mediate this function in anergic Th1 clones. We report that anergic Th1 clones do indeed express a genetic program different from that of responsive T cells. Moreover, one gene, the general receptor of phosphoinositides 1 (GRP1), was selectively induced in anergic T cells. The GRP1, located in the plasma membrane, regulated integrin-mediated adhesion and was invariably associated with unresponsiveness in multiple models of anergy, T cells expressing retrovirally transduced GRP1 exhibited normal proliferation and cytokine production. However, GRP1-transduced T cells mere not stable and rapidly lost GRP1 expression, Thus, although GRP1 may not directly mediate T cell anergy, it regulates cell expansion and survival, perhaps through its integrin-associated activities. C1 Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Munich, Gene Ctr, Mol Biol Lab, Munich, Germany. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Bluestone, JA (reprint author), Univ Chicago, Ben May Inst Canc Res, 5841 S Maryland Ave,MC 1089, Chicago, IL 60637 USA. FU NCI NIH HHS [CA40046]; NIAID NIH HHS [P01AI35294-6] NR 75 TC 27 Z9 29 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 308 EP 318 PG 11 WC Immunology SC Immunology GA 266VP UT WOS:000084321200043 PM 10605025 ER PT J AU Sada, K Zhang, J Siraganian, RP AF Sada, K Zhang, J Siraganian, RP TI Point mutation of a tyrosine in the linker region of Syk results in a gain of function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-ANTIGEN RECEPTOR; AFFINITY IGE RECEPTOR; FC-EPSILON-RI; PHOSPHOTYROSINE-BINDING DOMAIN; MEDIATED SIGNAL-TRANSDUCTION; ACTIVATION MOTIF; KINASE P72(SYK); INTEGRIN ALPHA(IIB)BETA(3); PROTOONCOGENE PRODUCT; CA2+ MOBILIZATION AB The protein tyrosine kinase Syk plays an essential role in Fc epsilon RI-mediated histamine release in mast cells by regulating the phosphorylation of other proteins. We investigated the functional role of a putative Syk phosphorylation site, Tyr(317). This tyrosine in the linker region of Syk is a possible site for binding by the negative regulator Chi, Syk with Tyr(317) mutated to Phe (Y317F) was expressed in a Syk-negative variant of the RBL-2H3 mast cells. Compared with cells expressing wild-type Syk, expression of the Y317F mutant resulted in an increase in the Fc epsilon RI-mediated tyrosine phosphorylation of phospholipase C-gamma and a dramatic enhancement of histamine release. The in vivo Fc epsilon RI-induced tyrosine phosphorylation of wild-type Syk and that of the Y317F mutant were similar. Although the FceRI-induced tyrosine phosphorylation of total cellular proteins was enhanced in the cells expressing the Y317F Syk, the phosphorylation of some other molecules, including the receptor subunits, Vav and mitogen-activated protein kinase, was not increased, The Fc epsilon RI-induced phosphorylation of Cbl was downstream of Syk kinase activity and was unchanged by expression of the Y317F mutation. These data indicate that Tyr(317) in the linker region of Syk functions to negatively regulate the signals leading to degranulation. C1 NIH, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Sada, K (reprint author), NIH, Receptors & Signal Transduct Sect, Oral Infect & Immun Branch, Natl Inst Dent & Craniofacial Res, Bldg 10,1N106, Bethesda, MD 20892 USA. RI Sada, Kiyonao/H-7373-2015 OI Sada, Kiyonao/0000-0001-6124-3100 NR 63 TC 49 Z9 50 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 338 EP 344 PG 7 WC Immunology SC Immunology GA 266VP UT WOS:000084321200046 PM 10605028 ER PT J AU Link, AA Kino, T Worth, JA McGuire, JL Crane, ML Chrousos, GP Wilder, RL Elenkov, IJ AF Link, AA Kino, T Worth, JA McGuire, JL Crane, ML Chrousos, GP Wilder, RL Elenkov, IJ TI Ligand-activation of the adenosine A2a receptors inhibits IL-12 production by human monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TNF-ALPHA PRODUCTION; T-CELL ACTIVATION; INTERLEUKIN-12; RELEASE; INJURY; ISCHEMIA; IMMUNITY; INNATE; MICE; REPERFUSION AB Adenosine (ADO) exerts potent anti-inflammatory and immunosuppressive effects. In this paper we address the possibility that these effects are partly mediated by inhibition of the secretion of IL-12, a proinflammatory cytokine and a major inducer of Th1 responses. We demonstrate that 5'-N-ethylcarboxamidoadenosine (NECA), a nonspecific ADO analogue, and 2-p-(2-carbonylethyl)phenylethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680), a specific A2a receptor agonist, dose-dependently inhibited, in whole blood ex vivo and monocyte cultures, the production of human IL-12 induced by LPS and Stapholococcus aureus Cowan strain 1, However, the Al receptor agonist 2-Chloro-N-6-cyclopentyladenosine and the A3 receptor agonists N-6-Benzyl-NECA and 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-yl]-N-methyl-beta-D-ribofuranuronamide expressed only weak inhibitory effects. On the other hand, NECA and CGS-21680 dose-dependently potentiated the production of IL-10, The differential effect of these drugs on monocyte IL-12 and IL-10 production implies that these effects are mediated by A2a receptor signaling rather than by intracellular toxicity of ADO analogue's metabolites. Moreover, CGS-21680 inhibited IL-12 production independently of endogenous IL-10 induction, because anti-IL-10 Abs failed to prevent its effect, The selective A2a antagonist 8-(3-Chlorostyryl) caffeine prevented the inhibitory effect of CGS-21680 on IL-12 production, The phosphodiesterase inhibitor Ro 20-1724 dose-dependently potentiated the inhibitory effect of CGS-21680 and, furthermore, Rp-cAMPS, a protein kinase A inhibitor, reversed the inhibitory effect of CGS-21680, implicating a cAMP/protein kinase A pathway in its action. Thus, ligand activation of A2a receptors simultaneously inhibits IL-12 and stimulates IL-10 production by human monocytes, Through this mechanism, ADO released in excess during inflammatory and ischemic conditions, or tissue injury, may contribute to selective suppression of Th1 responses and cellular immunity. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Elenkov, IJ (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N240,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. NR 36 TC 161 Z9 164 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 436 EP 442 PG 7 WC Immunology SC Immunology GA 266VP UT WOS:000084321200058 PM 10605040 ER PT J AU Panelli, MC Riker, A Kammula, U Wang, E Lee, KH Rosenberg, SA Marincola, FM AF Panelli, MC Riker, A Kammula, U Wang, E Lee, KH Rosenberg, SA Marincola, FM TI Expansion of tumor-T cell pairs from fine needle aspirates of melanoma metastases SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; INFILTRATING LYMPHOCYTES; MONOCLONAL-ANTIBODIES; PERIPHERAL-BLOOD; ANTIGEN MART-1; LYMPH-NODES; HLA-A; EXPRESSION; PEPTIDE; RECOGNITION AB Lymphocytes expanded fi om excised specimens can be used to characterize intratumoral T cell responses. These analyses, however, are limited to one time point in the natural history of the removed tumor. The expansion of autologous tumor cells and tumor-infiltrating lymphocytes (TIL) from fine needle aspirates (FNA) of tumors potentially allows a dynamic evaluation of T cell responses within the same lesion at moments relevant to the disease course or response to therapy. Fourteen TIL cultures and 8 tumor cell lines cr ere generated from 18 FNA (12 patients). Five of six Tn that could be tested against autologous tumor demonstrated specific reactivity. Two additional TIL for which no autologous tumor was available demonstrated recognition of HLA-matched melanoma cell lines. Serial FNA of the same lesions were performed in five HLA-A*0201 patients vaccinated with the emulsified melanoma Ag (MA) epitopes: MART-1:27-35; tyrosinase:368-376(370D); gp100:280-288(288V); and gp100:209-217 (210M). FNA material was separately cultured for a short time in IL-2 (300 IU/ml) after stimulation with irradiated autologous PBMC pulsed with each peptide or FluM1:58-66 (1 mu mol/ml). No peptide-specific TIL could be expanded from prevaccination FN,I, However, after vaccination, TIL specific for gp100:280(g280), gp100:209 (g209), and MART-1:27-35 (MART-1)-related epitopes were identified in three, three, and two patients, respectively, No Flu reactivity could be elicited in TIL, whereas it was consistently present in Dal allel PBMC cultures, This excluded PBMC contamination of the FNA material. This analysis suggests the feasibility of TIL expansion from minimal FNA material and localization of vaccine-specific T cells at the tumor site. C1 NCI, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Div Clin Sci, Bldg 10,Room 2B42,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. RI Riker, Adam/A-6065-2011 NR 49 TC 58 Z9 60 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2000 VL 164 IS 1 BP 495 EP 504 PG 10 WC Immunology SC Immunology GA 266VP UT WOS:000084321200065 PM 10605047 ER PT J AU Kawakami, Y Dang, N Wang, X Tupesis, J Robbins, PF Wang, RF Wunderlich, JR Yannelli, JR Rosenberg, SA AF Kawakami, Y Dang, N Wang, X Tupesis, J Robbins, PF Wang, RF Wunderlich, JR Yannelli, JR Rosenberg, SA TI Recognition of shared melanoma antigens in association with major HLA-A alleles by tumor infiltrating T lymphocytes from 123 patients with melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma antigens; HLA-A alleles; tumor-infiltrating lymphocytes ID AUTOLOGOUS MELANOMA; METASTATIC MELANOMA; PEPTIDE EPITOPES; GENE; IDENTIFICATION; TYROSINASE; GP100; CELLS; IMMUNOTHERAPY; REJECTION AB A total of 123 tumor-infiltrating T lymphocyte (TIL) cultures established from patients with HLA-A1, -A2, -A3, -A24, or -A31 metastatic melanoma in the Surgery Branch, National Cancer Institute, were screened for recognition of shared melanoma antigens including five melanosomal proteins (tyrosinase, MART-1/melan-A. gp100, TRP1, TRP2) as well as peptides derived from MAGE-1 and MAGE-3. Examination of the specificity of these T cells indicated that 16% of HLA-A1 TIL, 57% of HLA-A2 TIL, 7% of HLA-A3 TIL, 13% of HLA-A24 TIL, and 27% of HLA-A31 TIL, recognized shared melanoma antigens restricted by major histocompatibility complex class I. Melanosomal proteins were frequently recognized by these TIL, and MART-1(27-35), gp100(154-162), gp100(209-217), and gp100(280-288) represent highly immunogenic epitopes that were recognized by a high percentage of HLA-A2 restricted melanoma reactive TIL. Recognition of gp100 by HLA-A2 restricted TIL significantly correlated with clinical response to adoptive immunotherapy with TIL in 21 HLA-A2 melanoma patients (p = 0.024). Four HLA-A1, two HLA-A2, two HLA-A3, one HLA-A24, and two HLA-A31 restricted shared antigen-specific TIL did not recognize the previously identified antigens tested in this study, and may be useful for the identification of new melanoma antigens. The observation that TILs isolated from patients with metastatic melanoma recognized melanosomal proteins in the context of predominant HLA-A alleles implies that it may be possible to develop immunotherapies for patients with melanoma expressing diverse HLA types. C1 NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Div Clin Sci, NIH, 9000 Rockville Pike,Bldg 10,Room 2B42, Bethesda, MD 20892 USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 45 TC 71 Z9 75 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 2000 VL 23 IS 1 BP 17 EP 27 DI 10.1097/00002371-200001000-00004 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 280WV UT WOS:000085127500003 PM 10687134 ER PT J AU Ladanyi, A Nishimura, MI Rosenberg, SA Yang, JC AF Ladanyi, A Nishimura, MI Rosenberg, SA Yang, JC TI Tumorigenicity and immunogenicity of murine tumor cells expressing an MHC class II molecule with a covalently bound antigenic peptide SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE MHC class II; CD4(+) lymphocytes; tumor antigens; vaccination ID COMPLEX CLASS-I; MELANOMA-ASSOCIATED ANTIGEN; T-LYMPHOCYTES RECOGNIZE; HLA-DR; INFILTRATING LYMPHOCYTES; INVARIANT CHAIN; CANCER-IMMUNOTHERAPY; REJECTION ANTIGEN; AUTOLOGOUS TUMOR; CLONES AB The significance of CD4(+) lymphocytes and major histocompatibility complex (MHC) class II-restricted antigens in antitumor immunity has been demonstrated in several animal models as well as in some human tumors. However, because of the lack of known class II-restricted antigens, the participation of CD4(+) cells in antitumor responses has not been well characterized. Recent reports showed that class II proteins covalently linked to an antigenic peptide could be constructed and cells expressing these fusion proteins were recognized by specific T-H cells. The aim of this study was to determine the effect of the expression of a class II-peptide construct on the tumorigenicity and immunogenicity of transfected murine tumor cells. We have constructed a gene for I-E-d beta chain covalently coupled to the I-E-d-restricted T-H cell determinant of sperm whale myoglobin (SWM132-145). This class II fusion protein was recognized by a specific T-H cell line on the surface of COS-7 cells or BALB/c sarcoma cells. The sarcoma cells expressing the MHC-peptide complex were rejected by immunocompetent BALB/c mice, and in vivo T-cell subset depletion experiments suggested the importance of CD4(+) cells in the rejection. Moreover, splenocytes from mice immunized with tumor cells expressing the I-E-d-SWM complex showed specific peptide recognition in vitro. Such covalent MHC-peptide complexes could prove useful in studies on the role of CD4(+) lymphocytes in antitumor immune responses, and also in designing new, more effective vaccine approaches to the immunotherapy of cancer, as class II-restricted tumor-associated antigens are identified for human cancers. C1 NCI, Surg Branch, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Surg Branch, Div Canc Treatment, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 43 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 2000 VL 23 IS 1 BP 36 EP 47 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 280WV UT WOS:000085127500005 PM 10687136 ER PT J AU Lin, J Panigraphy, D Trinh, LB Folkman, J Shiloach, J AF Lin, J Panigraphy, D Trinh, LB Folkman, J Shiloach, J TI Production process for recombinant human angiostatin in Pichia pastoris SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE angiostatin; Pichia pastoris ID METHANOL CONCENTRATION; FERMENTATION; ANGIOGENESIS; EXPRESSION; GENE; SUPPRESSION; CARCINOMA; PROTEIN AB A pilot-scale production method of recombinant human angiostatin, a 38-kD fragment of plasminogen which has been reported to have antiangiogenic activity, has been successfully established by expressing the protein in the methylotrophic yeast Pichia pastoris, The secreted protein inhibited cultured endothelial cell proliferation in vitro and Lewis lung carcinoma growth in mice. The fermentation process was carried out using an on-line methanol controller, administering methanol to the growing culture and keeping its concentration under 2 g L-1. The fermentation lasted 90 h, of which 70 h were growth on methanol. During growth on methanol the culture volume increased 64%, from 7 L to 11.5 L, producing 200 mg angiostatin and 5 kg of biomass. C1 NIDDK, Biotechnol Unit, LCDB, NIH, Bethesda, MD 20892 USA. Harvard Univ, Childrens Hosp, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Unit, LCDB, NIH, Bldg 6,Rm B1-33, Bethesda, MD 20892 USA. NR 18 TC 13 Z9 16 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD JAN PY 2000 VL 24 IS 1 BP 31 EP 35 DI 10.1038/sj.jim.2900766 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 311BJ UT WOS:000086864300006 ER PT J AU Schooley, RT Mladenovic, J Sevin, A Chiu, S Miles, SA Pomerantz, RJ Campbell, TB Bell, D Ambruso, D Wong, R Landay, A Coombs, RW Fox, L Kamoun, M Jacovini, J AF Schooley, RT Mladenovic, J Sevin, A Chiu, S Miles, SA Pomerantz, RJ Campbell, TB Bell, D Ambruso, D Wong, R Landay, A Coombs, RW Fox, L Kamoun, M Jacovini, J CA AIDS Clinical Trials Grp 285 Study TI Reduced mobilization of CD34(+) stem cells in advanced human immunodeficiency virus type 1 disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th International Congress on Drug Therapy in HIV Infection CY NOV 08-12, 1998 CL GLASGOW, SCOTLAND ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC PROGENITOR CELLS; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-BONE-MARROW; PERIPHERAL-BLOOD; NORMAL DONORS; IN-VITRO; T-CELL; HIV-1 REPLICATION; NORMAL VOLUNTEERS AB Granulocyte colony-stimulating factor (r-met Hu G-CSF; filgrastim; 10 mu g/kg/day for 7 days) was used to mobilize CD34(+) stem cells into the peripheral blood of human immunodeficiency virus type 1 (HIV-1)-infected individuals and a group of HIV-1-uninfected donors as a measure of immunologic reserve in HIV-1-infected people. G-CSF mobilized CD34(+) cells of HIV-1-infected individuals with cell counts >500 CD4(+) cells/mm(3), as well as in HIV-1-uninfected donors. In contrast, CD34(+) cell mobilization was significantly blunted in HIV-1-infected individuals with cell counts <500 CD4+ cells/mm(3) (<200 cell days vs. >650 cell days, P < .0005, compared with the >500 CD4(+) cell cohort). At least 1.75 X 10(7) CD34(+) cells were harvested by leukapheresis from patients in each study cohort. CD34(+) cell viability and the ability to differentiate precursor cells into myeloid and erythroid progenitor cells were not affected by HIV-1 infection. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Belle Bonfils Blood Ctr, Denver, CO 80262 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Ctr Human Virol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol, Philadelphia, PA 19107 USA. Social & Sci Syst, Rockville, MD USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Rush Med Ctr, Dept Immunol, Chicago, IL USA. Univ Washington, Dept Med, Seattle, WA USA. RP Schooley, RT (reprint author), Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Campus Box B 168,4200 E 9th Ave, Denver, CO 80262 USA. FU NIAID NIH HHS [AI 32783, AI 38858, AI 32770] NR 65 TC 24 Z9 24 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 2000 VL 181 IS 1 BP 148 EP 157 DI 10.1086/315168 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 282QJ UT WOS:000085229300019 PM 10608761 ER PT J AU Cooper, PJ Fekade, D Remick, DG Grint, P Wherry, J Griffin, GE AF Cooper, PJ Fekade, D Remick, DG Grint, P Wherry, J Griffin, GE TI Recombinant human interleukin-10 fails to alter proinflammatory cytokine production or physiologic changes associated with the Jarisch-Herxheimer reaction SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR; IMPAIRS HOST-DEFENSE; SEPTIC SHOCK; RELAPSING FEVER; FACTOR-ALPHA; PNEUMOCOCCAL PNEUMONIA; PROTECTS MICE; IL-10; ENDOTOXEMIA; LETHALITY AB Interleukin (IL)-10 may have a role in the treatment of cytokine-associated inflammatory syndromes. The Jarisch-Herxheimer reaction (J-HR), which follows antibiotic treatment of Borrelia recurrentis infection, is a useful model of acute systemic inflammation associated with a cytokine surge and characteristic pathophysiologic changes. In a double-blind, placebo-controlled study, 49 Ethiopian men with B. recurrentis infection were randomized to receive a single intravenous bolus of either 25 mu g/kg of recombinant human (rh) IL-10 or vehicle control shortly before receiving intramuscular penicillin. Patients were monitored for physiologic changes, and plasma samples were taken repeatedly for 24 h after treatment. rhIL-10 had no impact on changes in any of the physiologic parameters of J-HR, plasma cytokine levels, or the rate of spirochete clearance. A single intravenous bolus of 25 mu g/kg of rhIL-10 does not seem to have a useful role in the treatment of the J-HR associated with B, recurrentis infection. C1 Univ London St Georges Hosp, Sch Med, Div Infect Dis, London SW17 0RE, England. Univ Addis Ababa, Black Lion Hosp, Dept Internal Med, Addis Ababa, Ethiopia. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Cooper, PJ (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. NR 30 TC 21 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 2000 VL 181 IS 1 BP 203 EP 209 DI 10.1086/315183 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 282QJ UT WOS:000085229300026 PM 10608768 ER PT J AU Angus, CW Klivington-Evans, D Dubey, JP Kovacs, JA AF Angus, CW Klivington-Evans, D Dubey, JP Kovacs, JA TI Immunization with a DNA plasmid encoding the SAG1 (P30) protein of Toxoplasma gondii is immunogenic and protective in rodents SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT American-Society-of-Biochemistry-and-Molecular-Biology Annual Meeting CY MAY 15-20, 1998 CL WASHINGTON, D.C. SP Amer Soc Biochem & Molec Biol ID MAJOR SURFACE-ANTIGEN; P-30 ANTIGEN; T-CELLS; MICE; INFECTION; VACCINATION; IMMUNITY; VACCINES; MACROPHAGES; EXPRESSION AB Immunization with DNA can induce humoral and cell-mediated immune responses, both of which are important in conferring immunity to Taxoplasma gondii, The efficacy of genetic vaccination with a cDNA encoding the T. gondii SAG1 (P30) surface antigen was evaluated. Sera of immunized mice showed recognition of T. gondii tachyzoites by immunofluorescence and exhibited high titers of antibody to SAG1 by ELISA, SAG1-stimulated splenocytes from vaccinated mice produced primarily interferon-gamma and interleukin-2, Vaccinated mice survived challenge with 80 tissue cysts of ME49 strain, whereas all control mice died; challenge with 20 tissue cysts resulted in fewer brain cysts, compared with controls, Challenge of vaccinated rats with VEG strain oocysts resulted in a reduction in brain cysts. No protection was observed when mice were challenged with the highly virulent RH strain tachyzoites, These results suggest that nucleic acid vaccination can provide protection against T. gondii infection in mice. C1 NIH, Dept Crit Care Med, Off Review, NCRR, Bethesda, MD 20892 USA. ARS, Parasite Biol & Epidemiol Lab, Inst Livestock & Poultry Sci, USDA, Beltsville, MD USA. RP Angus, CW (reprint author), NIH, Dept Crit Care Med, Off Review, NCRR, 6705 Rockledge Dr,Suite 6104, Bethesda, MD 20892 USA. NR 34 TC 77 Z9 93 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 2000 VL 181 IS 1 BP 317 EP 324 DI 10.1086/315186 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 282QJ UT WOS:000085229300039 PM 10608781 ER PT J AU Connick, E Lederman, MM Kotzin, BL Spritzler, J Kuritzkes, DR St Clair, M Sevin, AD Fox, L Chiozzi, MH Leonard, JM Rousseau, F Roe, JD Martinez, A Kessler, H Landay, A AF Connick, E Lederman, MM Kotzin, BL Spritzler, J Kuritzkes, DR St Clair, M Sevin, AD Fox, L Chiozzi, MH Leonard, JM Rousseau, F Roe, JD Martinez, A Kessler, H Landay, A TI Immune reconstitution in the first year of potent antiretroviral therapy and its relationship to virologic response SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th Conference on Retroviruses and Opportunistic Infections CY FEB 01-05, 1998 CL CHICAGO, ILLINOIS ID T-CELL FUNCTION; HUMAN-IMMUNODEFICIENCY-VIRUS; LOAD REDUCTION; HIV-1 DISEASE AB The effects of 1 year of zidovudine, lamivudine, and ritonavir treatment on immune reconstitution were evaluated in 34 human immunodeficiency virus (HIV)-infected individuals. After 48 weeks of therapy, 20 (59%) subjects had <100 copies HIV RNA/mL. CD4(+) T cells increased from a median of 192/mm(3) at baseline to 362/mm(3) at week 48, Lymphocyte proliferative responses to Candida normalized within 12 weeks, but responses to HIV and tetanus remained depressed throughout therapy. Alloantigen responses increased within 12 weeks and then declined to baseline levels. Recovery of delayed-type hypersensitivity responses occurred after 12 weeks for Candida and after 48 weeks for mumps. The magnitude of virologic suppression was correlated with numeric increases in CD4(+) T cells, but not with measures of functional immune reconstitution, Plasma virus suppression <100 copies/mL was not significantly correlated with increases in CD4(+) T cells or functional immune reconstitution. C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA. Vet Adm Med Ctr, Div Infect Dis, Denver, CO USA. Vet Adm Med Ctr, Div Clin Immunol, Denver, CO USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Glaxo Wellcome Inc, Durham, NC USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. NIAID, Div AIDS, NIH, Rockville, MD USA. Social & Sci Syst Inc, Rockville, MD USA. Abbott Labs, Abbott Pk, IL 60064 USA. Rush Med Coll, Dept Immunol Microbiol, Chicago, IL 60612 USA. Rush Med Coll, Infect Dis Sect, Chicago, IL 60612 USA. RP Connick, E (reprint author), Univ Colorado, Hlth Sci Ctr, Box B168,4200 E 9th Ave, Denver, CO 80220 USA. FU NIAID NIH HHS [AI-25879, AI-25915, AI-32770] NR 14 TC 139 Z9 143 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 2000 VL 181 IS 1 BP 358 EP 363 DI 10.1086/315171 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 282QJ UT WOS:000085229300047 PM 10608789 ER PT J AU Chen, YM Ting, CC Peng, JW Yang, WK Yang, KY Tsai, CM Perng, RP AF Chen, YM Ting, CC Peng, JW Yang, WK Yang, KY Tsai, CM Perng, RP TI Restoration of cytotoxic T lymphocyte function in malignant pleural effusion: Interleukin-15 vs. interleukin-2 SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID LUNG-CANCER PATIENTS; CELL GROWTH-FACTOR; IN-VIVO; IL-15; INDUCTION; PROLIFERATION; ACTIVATION; RECEPTOR AB The present study attempts to define the role of interleukin-15 (IL-15), as compared with IL-2, in generating cytotoxic T lymphocytes (CTL) from the malignant effusions of cancer patients. Effusion-associated lymphocytes (EAL) from malignant effusion were incubated with IL-15 or IL-2 with or without alpha CD3. Proliferation and cytotoxicity assays mere performed. IL-15 was found to have at least an equivalent, if not higher, activity to IL-2 in terms of lymphocyte proliferation and generation of CTL from EAL, The proliferative response of EAL, cocultured with IL-15, with or without alpha CD3, was partly inhibited by pretreatment with an anti-IL-2 receptor beta chain monoclonal antibody (mAb), The proliferative response of EAL, cocultured with alpha CD3, IL-2, or both, was partly inhibited by pretreatment with an anti-IL-2 receptor alpha chain mAb, Overnight [Cr-51] release assays against K562, Daudi, and the patients' autologous tumor cells were done to evaluate EAL's cytolytic activity. MHC class I Ab blocked the stimulated cytolytic activity of EAL against autologous tumors. An mAb depletion assay showed that the phenotype of the restored EAL was CD16(-)CD4(-)CD8(+); thus, the restored activity of EAL was CTL activity. The results suggest that both IL-15 and IL-2 can restore CTL activity from EAL in the presence of T cell receptor (TCR)-CD3 engagement, but the effect of IL-15 was superior. C1 Vet Gen Hosp, Chest Dept, Taipei, Taiwan. Natl Yang Ming Univ, Sch Med, Taipei, Taiwan. NCI, Lab Immune Cel Biol, NIH, Bethesda, MD 20892 USA. Natl Hlth Res Inst, Div Canc Res, Taipei, Taiwan. RP Chen, YM (reprint author), Vet Gen Hosp, Chest Dept, Shih Pai Rd, Taipei, Taiwan. NR 19 TC 16 Z9 17 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JAN PY 2000 VL 20 IS 1 BP 31 EP 39 DI 10.1089/107999000312711 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 278WX UT WOS:000085012900005 PM 10670650 ER PT J AU Lazarova, Z Hsu, R Yee, C Yancey, KB AF Lazarova, Z Hsu, R Yee, C Yancey, KB TI Human anti-laminin 5 autoantibodies induce subepidermal blisters in an experimental human skin graft model SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE autoimmunity; basement membrane zone; bullous disease; pemphigoid ID EPIDERMAL BASEMENT-MEMBRANE; ANCHORING FILAMENTS; ADHESION; INTEGRIN; KALININ; EPILIGRIN; HEMIDESMOSOMES; AUTOIMMUNE; MOLECULES; DISEASES AB Patients with one form of cicatricial pemphigoid have IgG antibasement membrane autoantibodies against laminin 5 (alpha 3 beta 3 gamma 2). Although passive transfer of rabbit anti-laminin 5 IgG to neonatal mice has been shown to induce subepidermal blisters that mimic those in patients, it has not been possible to directly assess the pathogenic activity of human autoantibodies in this animal model because the latter do not bind murine skin. To address this question, a disease model in adult mice as well as SCID mice bearing human skin grafts was developed. Adult BALB/C mice challenged with rabbit anti-laminin 5 IgG developed, in a concentration-related fashion, erythema, erosions, and crusts surrounding injection sites, histologic evidence of noninflammatory, subepidermal blisters, and deposits of rabbit IgG and murine C3 in epidermal basement membranes. Anti-laminin 5 IgG also induced subepidermal blisters in: adult complement-, mast cell-, and immuno-deficient mice; adult BALB/C mice pretreated with dexamethasone; and human skin grafts on SCID mice. Alterations did not develop in matching controls challenged with identical amounts of purified normal rabbit IgG or bovine serum albumin. Using this adult mouse model, human skin grafts on SCID mice were challenged with purified IgG from patients with alpha subunit-specific, anti-laminin 5 autoantibodies, or normal controls. Patient (but not control) IgG induced epidermal fragility as well as noninflammatory, subepidermal blisters in grafted human (but not adjacent murine) skin. Moreover, whereas all mice that received patient autoantibodies had anti-laminin 5 IgG in their circulation, deposits of human IgG were present only in the epidermal basement membranes of grafts. Interestingly, these in situ and circulating autoantibodies were predominately of the IgG(4) subclass. These studies demonstrate that human anti-laminin 5 autoantibodies are pathogenic in vivo and describe an animal model that can be used to define disease pathomechanisms and biologically important domains within this autoantigen. C1 NCI, Dermatol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Yancey, KB (reprint author), NCI, Dermatol Branch, Div Clin Sci, NIH, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. NR 28 TC 51 Z9 51 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 BP 178 EP 184 DI 10.1046/j.1523-1747.2000.00829.x PG 7 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700029 PM 10620135 ER PT J AU Udey, MC AF Udey, MC TI Tgf beta 1 and Langerhans cell development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 BP 209 EP 209 PG 1 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700053 ER PT J AU Saeki, H Hwang, ST AF Saeki, H Hwang, ST TI Dermal expression of stromal cell-derived factor (SDF)-1 contributes to the recruitment of mature dendritic cells from skin to regional lymph nodes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 BP 210 EP 210 PG 1 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700057 ER PT J AU von Stebut, E Udey, MC AF von Stebut, E Udey, MC TI C57bl/6 (b6) and BALB/c skin-derived dendritic cells (DC) produce different amounts of IL-1 alpha DC-derived IL-1 alpha may antagonize TH2 development in mice that are genetically resistant to Leishmania major (L-major) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 BP 212 EP 212 PG 1 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700067 ER PT J AU Cohen, SS Kawamura, T Zoeteweij, JP Aquilino, EA Qalbani, M Orenstein, JM Neurath, AR Blauvelt, A AF Cohen, SS Kawamura, T Zoeteweij, JP Aquilino, EA Qalbani, M Orenstein, JM Neurath, AR Blauvelt, A TI HIV primary isolate infection of immature Langerhans cells within epithelial tissue explants: a novel model to study early biologic events involved in sexual transmission of HIV SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. New York Blood Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 BP 218 EP 218 PG 1 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700101 ER PT J AU Kawamura, T Qalbani, M Orenstein, JM Blauvelt, A AF Kawamura, T Qalbani, M Orenstein, JM Blauvelt, A TI Human monocyte-derived dendritic cells propagated in the presence of GM-CSF, IL4, and TGF beta 1 morphologically, phenotypically, and functionally resemble resident epidermal Langerhans cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 MA 067 BP 221 EP 221 PG 1 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700119 ER PT J AU Yang, D Howard, OMZ Chertov, O Chen, Q Bykovskaia, SN Shogan, J Anderson, M Schroder, JM Wang, JM Oppenheim, JJ AF Yang, D Howard, OMZ Chertov, O Chen, Q Bykovskaia, SN Shogan, J Anderson, M Schroder, JM Wang, JM Oppenheim, JJ TI CCR6 is expressed by both CD34(+) progenitor-derived and monocyte-derived human immature dendritic cells and serves as a receptor for human beta-defensins SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Mol Immunoregulat Lab, DBS, FCRDC, Frederick, MD 21701 USA. Allegheny Univ Hlth Sci, Pittsburgh, PA USA. Magainin Res Inst, Plymouth Meeting, PA USA. Univ Kiel, Dept Dermatol, D-2300 Kiel, Germany. RI Schroeder, Jens/B-3994-2009; Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 MA 075 BP 222 EP 222 PG 1 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700126 ER PT J AU Marovich, MA McDowell, MA Nutman, TB Sacks, DL AF Marovich, MA McDowell, MA Nutman, TB Sacks, DL TI Infectious stage Leishmania major induction of IL-12p70 in huma dendritic cells is CD401 dependent SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2000 VL 114 IS 1 MA 158 BP 236 EP 236 PG 1 WC Dermatology SC Dermatology GA 276GF UT WOS:000084866700210 ER PT J AU Sandoval, CM Liow, K Feuillan, PP Biesecker, LG Theodore, WH AF Sandoval, CM Liow, K Feuillan, PP Biesecker, LG Theodore, WH TI Neuroendocrine changes in gelastic seizure with hypothalmic hamartoma. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NINDS, Epilepsy Res Branch, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NHGRI, Lab Genet Dis Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 150 BP 28A EP 28A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600158 ER PT J AU Langer, DA Housseau, F Levitsky, HI Pardoll, DM Topalian, ST AF Langer, DA Housseau, F Levitsky, HI Pardoll, DM Topalian, ST TI Characterization of prostate carcinoma reactive T lymphocytes. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Univ Colorado, Sch Med, HHMI, NIH, Denver, CO USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 429 BP 79A EP 79A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600433 ER PT J AU Nickles, AL Fox, E Adamson, PC AF Nickles, AL Fox, E Adamson, PC TI An in vitro model to examine the schedule dependence of methotrexate and trimetrexate in osteosarcoma. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2000 VL 48 IS 1 SU S MA 464 BP 85A EP 85A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 302CD UT WOS:000086346600468 ER PT J AU Moutsopoulos, NM Wild, T Horn, J Orenstein, JM Wahl, SM AF Moutsopoulos, NM Wild, T Horn, J Orenstein, JM Wahl, SM TI Enhanced susceptibility of tonsil lymphoid cells to HIV infection in vivo and in vitro. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC 20037 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 2 BP 10 EP 10 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200004 ER PT J AU Pessach, I Leto, TL Levy, R AF Pessach, I Leto, TL Levy, R TI Essential requirement of cytosolic phospholipase A(2) for stimulation of NADPH oxidase diaphorase activity in granulocyte like cells. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Ben Gurion Univ Negev, Soroka Med Ctr, Beer Sheva, Israel. 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 43 BP 17 EP 17 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200043 ER PT J AU Kamohara, H Yamashiro, S Yoshimura, T AF Kamohara, H Yamashiro, S Yoshimura, T TI Induction of discoidin domain receptor 1 (DDR1) in human leukocytes. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 48 BP 18 EP 18 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200051 ER PT J AU Yang, D Chertov, O Rosenberg, HF Chen, Q Anderson, M Schroder, JM Oppenheim, JJ AF Yang, D Chertov, O Rosenberg, HF Chen, Q Anderson, M Schroder, JM Oppenheim, JJ TI Mobilization of various types of leukocytes by human granulocyte-derived antimicrobial proteins: Identification of novel activities and/or receptors for defensins, cathelicidin, and eosinophil-derived neurotoxin (EDN) SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NIAID, NIH, Bethesda, MD 20892 USA. Magainin Res Inst, Plymouth Meeting, PA 19642 USA. Univ Kiel, Dept Dermatol, D-24103 Kiel, Germany. RI Schroeder, Jens/B-3994-2009 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 63 BP 20 EP 20 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200062 ER PT J AU Wang, JM Le, Y Oppenheim, JJ AF Wang, JM Le, Y Oppenheim, JJ TI New insights into the role of formyl peptide receptors: Implications for AIDS and Alzheimer's disease SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, LMI,DBS, NIH, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 69 BP 21 EP 21 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200068 ER PT J AU McCartney-Francis, N Mizel, D Wahl, S AF McCartney-Francis, N Mizel, D Wahl, S TI Enhanced Toll-like receptor (TLR4) expression in TGF-beta 1 null mice. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NIDCR, 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 75 BP 22 EP 22 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200074 ER PT J AU Yoshimura, T Yamashiro, S Wang, JM Yang, D Gong, WH Kamohara, H AF Yoshimura, T Yamashiro, S Wang, JM Yang, D Gong, WH Kamohara, H TI Human PMN can be driven by selected cytokines to acquire some of the phenotypic and functional features of dendritic cells. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 74 BP 22 EP 22 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200076 ER PT J AU Askenase, PW Kawikova, I Ramabhadran, R Akahira-Azuma, M Taub, D Hugli, TE Gerard, C Tsuji, RF AF Askenase, PW Kawikova, I Ramabhadran, R Akahira-Azuma, M Taub, D Hugli, TE Gerard, C Tsuji, RF TI Innate immunity is required for recruitment of acquired T cell immunity in contact sensitivity SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT 06405 USA. NIH, Inst Aging, Baltimore, MD 21224 USA. Scripps Res Inst, La Jolla, CA USA. Harvard Univ, Boston, MA 02115 USA. Noda Inst, Tokyo 278, Japan. 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 100 BP 26 EP 26 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200101 ER PT J AU Fang, JY Mikovits, JA Bagui, R Ruscetti, FW AF Fang, JY Mikovits, JA Bagui, R Ruscetti, FW TI Hut 78 cell: DNA methyltransferase and HIV-1 infection SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, NIH, Lab Leukocyte Biol, 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2000 SU S MA 116 BP 29 EP 29 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 353CY UT WOS:000089257200118 ER PT J AU Issaq, HJ AF Issaq, HJ TI Untitled - Foreword SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Editorial Material C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Issaq, HJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 1 BP VII EP VIII PG 2 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 274MD UT WOS:000084768900001 ER PT J AU Yuan, HM Janini, GM Issaq, HJ Thompson, RA Ellison, DK AF Yuan, HM Janini, GM Issaq, HJ Thompson, RA Ellison, DK TI Separation of closely related heptadecapeptides by micellar electrokinetic chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID CAPILLARY ZONE ELECTROPHORESIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; CLOSELY-RELATED PEPTIDES; NONIONIC SURFACTANT; MASS; SELECTIVITY; PROTEINS; ANALOGS; CHARGE AB Separations of five synthetic heptadecapeptides from the p-loop region of p21 Ras proteins, differing mostly in a single amino acid at the same position, were investigated. The studies were performed at low pHs in polyacryamide-coated capillaries, where the peptides were slightly positively charged. CZE, without surfactants, failed to separate all the peptides. Separations by MEKC employing an anionic surfactant sodium dodecyl sulfate (SDS), a neutral surfactant Tween 20 and a cationic surfactant cetyltrimethylammonium bromide (CTAB) provided results with varying degrees of success. Tween 20, slightly improved the separation while CTAB resulted in almost baseline separation of all the peptides. The effects of applying acetonitrile to MEKC were also examined. The separation results are analyzed with regard to the properties of the peptides and the surfactants. Implications of the results on peptide-micelle interactions and general aspects of peptide separation by MEKC are discussed. C1 Merck & Co Inc, Merck Res Labs, Analyt Res Dept, Rahway, NJ 07065 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Yuan, HM (reprint author), Merck & Co Inc, Merck Res Labs, Analyt Res Dept, Rahway, NJ 07065 USA. NR 27 TC 4 Z9 4 U1 2 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 1 BP 127 EP 143 DI 10.1081/JLC-100101440 PG 17 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 274MD UT WOS:000084768900011 ER PT J AU Issaq, HJ Chan, KC Janini, GM Muschik, GM AF Issaq, HJ Chan, KC Janini, GM Muschik, GM TI Multidimensional multimodal instrumental separation of complex mixtures SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID CAPILLARY ZONE ELECTROPHORESIS; CHROMATOGRAPHY; PEPTIDES AB Presented here is a simple approach to the application of HPLC/CE for the separation of complex mixtures. A two-dimensional HPLC/CE instrumental setup was assembled from commercially available equipment. Fractions of the effluent from the HPLC system are collected into microtiter plates with the aid of a microfraction collector which allows the collection of samples by time, drops, or external signal (peaks). The fractions are then dried under vacuum at room temperature in a special unit, reconstituted, and analyzed by CZE. Any size or type of HPLC or CE column can be used with no limitation on the amount of sample injected into the HPLC. Any CE detection procedure, such as LIF, MS, UV, or other, can be used. This setup is practical, simple, robust, and allows the separation of complex mixtures. Preliminary results show the utility of this system for the analysis of a mixture of two protein digests, cytochrome C and myoglobin. C1 NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 1 BP 145 EP 154 DI 10.1081/JLC-100101441 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 274MD UT WOS:000084768900012 ER PT J AU Ito, Y AF Ito, Y TI Continuous flow method for monitoring protein precipitation by ammonium sulfate SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB I have proposed "Centrifugal Precipitation Chromatography"(1) as a new method for the precipitation of proteins using a linear gradient of ammonium sulfate (AS). However data on the solubility of proteins under these specific conditions are not available. Therefore, the following method is proposed to obtain these data. It uses an HPLC pump to form a linear concentration gradient between a protein solution and a concentrated ammonium sulfate (AS) solution (90% saturation) which is continuously monitored with a uv detector at 280 nm. At a low flow rate of 0.1 mL/min the protein is exposed to a gradually increasing AS concentration until it reaches the critical point where precipitation takes place. The resulting light scattering increases the absorbance reading to form a distinct peak on the uv gradient curve where the valley and summit of the peak correspond to the starting and ending points of the protein precipitation, respectively. The method has been tested with a set of stable proteins at various pHs and ionic strengths of potassium phosphate buffer. Ten protein samples tested may be divided into two groups: The first group represented by albumin precipitates at 60-70% AS saturation and decreases in solubility at an acidic pH. The second group includes globulins which precipitate at 35-40% AS saturation and tend to increase their solubility at an acidic pH. The present method may be improved by the use of a nephelometric detection system with a small capacity flow cell. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP NHLBI, Biophys Chem Lab, NIH, Bldg 10,Rm 7N322, Bethesda, MD 20892 USA. NR 2 TC 6 Z9 6 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6076 EI 1520-572X J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 2 BP 241 EP 249 DI 10.1081/JLC-100101448 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 274MH UT WOS:000084769300005 ER PT J AU Weiss, E Ziffer, H Ito, Y AF Weiss, E Ziffer, H Ito, Y TI Use of countercurrent chromatography (CCC) to separate mixtures of artemisinin, artemisitene, and arteannuin B SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID QINGHAOSU AB A series of solvent systems was developed for CCC to separate mixtures containing variable amounts of artemisinin, artemisitene, and arteannuin B. To purify multigram quantities of artemisinin by CCC it was necessary to maximize the amount of a mixture that could be dissolved in a fixed quantity of the solvent mixture. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NHLB, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Weiss, E (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,B1-31, Bethesda, MD 20892 USA. NR 6 TC 5 Z9 5 U1 4 U2 6 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 6 BP 909 EP 913 DI 10.1081/JLC-100101497 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 304PK UT WOS:000086492500007 ER PT J AU Shinomiya, K Hirozane, S Kabasawa, H Ito, Y AF Shinomiya, K Hirozane, S Kabasawa, H Ito, Y TI Protein separation by cross-axis coil planet centrifuge with two different positions of eccentric coil assemblies using polyethylene glycol-dextran solvent system SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID POLYMER PHASE SYSTEMS; PREPARATIVE COUNTERCURRENT CHROMATOGRAPHY; STATIONARY-PHASE; ROTARY SEALS; APPARATUS; DESIGN; ACCELERATION; EFFICIENCY; RETENTION; COLUMNS AB Countercurrent chromatography (CCC) of proteins was performed by the cross-axis coil planet centrifuge (cross-axis CPC) using polyethylene glycol (PEG) - dextran biphasic systems. A pair of eccentric coil assemblies was mounted at two different positions (off-center and central) on the rotary frame. The best separation was obtained from a two-phase solvent system composed of 4.0% (w/w) PEG 8000 - 5.0% (w/w) dextran T500 in 5 mM potassium phosphate buffer (pH 7.0) and 3 M sodium chloride using the upper PEG-rich phase as the mobile phase. The off-center column position yielded substantially better peak resolution between lysozyme and myoglobin than that obtained from the central position under otherwise identical conditions. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. NR 15 TC 8 Z9 8 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 7 BP 1119 EP 1129 DI 10.1081/JLC-100101513 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 309QM UT WOS:000086780200012 ER PT J AU Shinomiya, K Komatsu, T Murata, T Kabasawa, Y Ito, Y AF Shinomiya, K Komatsu, T Murata, T Kabasawa, Y Ito, Y TI Countercurrent chromatographic separation of vitamins by cross-axis coil planet centrifuge with eccentric coil assemblies SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID ROTARY SEALS; EFFICIENCY; APPARATUS; PHASE AB Vitamins were resolved by high-speed countercurrent chromatography using a cross-axis coil planet centrifuge equipped with eccentric coil assemblies. A two-phase solvent system composed of 1-butanol/ethanol/aqueous 0.15 M monobasic potassium phosphate (8:3:8) was used for the separation of water-soluble vitamins such as thiamine nitrate, pyridoxine hydrochloride, and nicotinamide, while 2,2,4-trimethyl pentane (isooctane)/methanol (1:1) was used for the separation of fat-soluble vitamins such as calciferol, vitamin A acetate, and (+/-)-alpha-tocopherol acetate. Overall results of experiments revealed that the cross-axis coil planet centrifuge is useful for the separation of vitamins by selecting suitable two-phase solvent systems. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. SS Pharmaceut Corp, Chuo Ku, Tokyo 1030007, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. NR 9 TC 8 Z9 9 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 9 BP 1403 EP 1412 DI 10.1081/JLC-100100423 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 317ZE UT WOS:000087257700009 ER PT J AU Shinomiya, K Sasaki, Y Shibusawa, Y Kishinami, K Kabasawa, Y Ito, Y AF Shinomiya, K Sasaki, Y Shibusawa, Y Kishinami, K Kabasawa, Y Ito, Y TI Countercurrent chromatographic separation of hippuric acid and related compounds using cross-axis coil planet centrifuge with eccentric coil assemblies SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID POLYMER PHASE SYSTEMS; PROTEIN SEPARATION; ROTARY SEALS; EFFICIENCY; APPARATUS; COLUMNS; SPEED AB Countercurrent chromatographic separation of hippuric acid (HA) and related compounds was performed using the cross-axis coil planet centrifuge equipped with a pair of eccentric coil assemblies mounted in an off-center position. Partition coefficients of HA and a set of related compounds were determined on a polar two-phase solvent system composed of methyl t-butyl ether, 1-butanol, acetonitrile and aqueous 0.1% trifluoroacetic acid at various volume ratios. The optimal volume ratio of 1 : 0 : 0 : 1 was successfully used to resolve p-amino HA, HA, p-methyl HA, and (+/-)-mandelic acid by the lower aqueous phase mobile, and benzoic acid, p-methyl HA and HA by the upper organic phase mobile. C1 Nihon Univ, Coll Pharm, Funabashi, Chiba 2748555, Japan. Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Analyt Chem, Tokyo 1920355, Japan. Showa Coll Pharmaceut Sci, Machida, Tokyo 1940042, Japan. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shinomiya, K (reprint author), Nihon Univ, Coll Pharm, 7-7-1 Narashinodai, Funabashi, Chiba 2748555, Japan. NR 13 TC 8 Z9 8 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 10 BP 1575 EP 1583 DI 10.1081/JLC-100100436 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 327AR UT WOS:000087770500010 ER PT J AU Sookkumnerd, T Hsu, JT Ito, Y AF Sookkumnerd, T Hsu, JT Ito, Y TI Purification of PEG-protein conjugates by centrifugal precipitation chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID POLYETHYLENE-GLYCOL; POLY(ETHYLENE GLYCOL); ATTACHMENT AB Preparative scale purification of PEG-protein conjugates by centrifugal precipitation chromatography is discussed. By utilizing the transport of ammonium sulfate across a membrane and the centrifugal force, an ammonium sulfate gradient is formed and used for differential precipitation of PEG-protein conjugates. Native proteins can be separated from PEG-protein conjugates by using this technique. C1 Lehigh Univ, Dept Chem Engn, Biopharmaceut Technol Inst, Bethlehem, PA 18015 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hsu, JT (reprint author), Lehigh Univ, Dept Chem Engn, Biopharmaceut Technol Inst, Bethlehem, PA 18015 USA. NR 17 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 13 BP 1973 EP 1979 DI 10.1081/JLC-100100466 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 347QQ UT WOS:000088941000004 ER PT J AU Patel, K Krishna, G Sokoloski, E Ito, Y AF Patel, K Krishna, G Sokoloski, E Ito, Y TI Preparative separation of curcuminoids from crude curcumin and turmeric powder by pH-zone-refining countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID CYTOCHROME-P450; CANCER AB Turmeric powder and its main component, curcumin, have a wide range of medicinal and culinary uses. The purpose of this study was to separate and purify curcumin from demethoxycurcumin and bis-demethoxycurcumin which are present in both turmeric powder, and commercial crude curcumin. The separation and purification of curcumin was accomplished through standard high-speed countercurrent chromatography (CCC) as well as pH-zone-refining CCC. The pH-zone-refining CCC technique was able to separate multi-gram quantities of curcumin and other curcuminoids from crude curcumin and turmeric powder, while maintaining a high level of purity. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Patel, K (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Room 7N322, Bethesda, MD 20892 USA. NR 17 TC 23 Z9 24 U1 1 U2 11 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 14 BP 2209 EP 2218 DI 10.1081/JLC-100100482 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 350JZ UT WOS:000089098700008 ER PT J AU Wu, CJ Du, QZ Ren, QL Ito, Y AF Wu, CJ Du, QZ Ren, QL Ito, Y TI Retention of stationary phase and partition efficiency of multilayer helical column rotated around its horizontal axis SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID COIL AB Using a multilayer helical separation column coaxially mounted on a horizontal rotary shaft, retention of the stationary phase and partition efficiency were studied at various rotation speeds ranging from 20 to 800 rpm. A binary two-phase solvent system composed of chloroform/water was used to elute the lower organic phase through the head of the rotating column. The results indicated that best retention of the stationary phase was obtained at a low rotation speed of 75 rpm yielding the highest peak resolution between caffeine and theophylline. Because of its simplicity and low rotation speed, the system has a potential to be scaled-up for an industrial-scale separation simply by increasing the capacity of the helical column. C1 Zhejiang Univ, Dept Chem Engn, Hangzhou 310027, Zhejiang, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Rm 7N322,10 Ctr Dr MSC 1676, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 14 BP 2219 EP 2224 DI 10.1081/JLC-100100483 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 350JZ UT WOS:000089098700009 ER PT J AU Du, QZ Wu, PD Ito, Y AF Du, QZ Wu, PD Ito, Y TI Van Deemter plot in high-speed countercurrent chromatography with a fixed volume of stationary phase SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB An adaptability of countercurrent chromatographic data to Van Deemter equation (H = A + B/u + Cu) is examined under a fixed volume of the stationary phase. Three lest samples, epigallochatechin gallate (EGCG), gallocatechin-gallate (GCG), and epicatechin gallate (ECG) were separated using a two-phase solvent system of n-hexane/ethyl acetate/water (3.5:1:10, v/v/v) at various linear flow rates (u). Our mathematical treatment produced a set of formulae, H-EGCG = 6.5 + 1/u + 6u; H-GCG = 6.5 + 1.3/u + 7u and H-ECG = 6.5 + 2.5/u + 9u, which showed excellent fit to the experimental data for each component. Constants B and C show high correlation with the partition coefficient values of three components. Based on the high correlation between log u and log H when u > 1, the plate height (H) for three components may be expressed by H = Du(k), where D is the plate height at u = 1 cm/s and k, the constant for each component. C1 Hangzhou Univ Commerce, Inst Food Engn, Hangzhou 310035, Peoples R China. Zhejiang Univ, Dept Chem Engn, Hangzhou 310027, Peoples R China. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Du, QZ (reprint author), Hangzhou Univ Commerce, Inst Food Engn, Hangzhou 310035, Peoples R China. NR 8 TC 4 Z9 4 U1 1 U2 8 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2000 VL 23 IS 19 BP 2929 EP 2935 DI 10.1081/JLC-100101833 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 380CF UT WOS:000165680200002 ER PT J AU Spencer, RGS Fishbein, KW AF Spencer, RGS Fishbein, KW TI Measurement of spin-lattice relaxation times and concentrations in systems with chemical exchange using the one-pulse sequence: Breakdown of the Ernst model for partial saturation in nuclear magnetic resonance spectroscopy SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE chemical exchange; one-pulse experiment; saturation factors; partial saturation; progressive saturation ID CREATINE-KINASE; NMR; HEART AB A fundamental problem in Fourier transform NMR spectroscopy is the calculation of observed resonance amplitudes for a repetitively pulsed sample, as first analyzed by Ernst and Anderson in 1966. Applications include determination of spin-lattice relaxation times (T-1's) by progressive saturation and correction for partial saturation in order to determine the concentrations of the chemical constituents of a spectrum. Accordingly, the Ernst and Anderson formalism has been used in innumerable studies of chemical and, more recently, physiological systems. However, that formalism implicitly assumes that no chemical exchange occurs. Here, we present an analysis of N sites in an arbitrary chemical exchange network, explicitly focusing on the intermediate exchange rate regime in which the spin-lattice relaxation rates and the chemical exchange rates are comparable in magnitude. As a special case of particular importance, detailed results are provided for a system with three sites undergoing mutual exchange. Specific properties of the N-site network are then detailed. We find that (i) the Ernst and Anderson analysis describing the response of a system to repetitive pulsing is inapplicable to systems with chemical exchange and can result in large errors in T, and concentration measurements; (ii) T-1's for systems with arbitrary exchange networks may still be correctly determined from a one-pulse experiment using the Ernst formula, provided that a short interpulse delay time and a large flip angle are used; (iii) chemical concentrations for exchanging systems may be correctly determined from a one-pulse experiment either by using a short interpulse delay time with a large flip angle, as for measuring T-1's, and correcting for partial saturation by use of the Ernst formula, or directly by using a long interpulse delay time to avoid saturation; (iv) there is a significant signal-to-noise penalty for performing one-pulse experiments under conditions which permit accurate measurements of T-1's and chemical concentrations. The present results are analogous to but are much more general than those that we have previously derived for systems with two exchanging sites. These considerations have implications for the design and interpretation of one-pulse experiments for all systems exhibiting chemical exchange in the intermediate exchange regime, including virtually all physiologic samples. C1 NIA, NIH, Baltimore, MD 21224 USA. RP Spencer, RGS (reprint author), NIA, NIH, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Fishbein, Kenneth/0000-0002-6353-4603 NR 17 TC 42 Z9 42 U1 1 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2000 VL 142 IS 1 BP 120 EP 135 DI 10.1006/jmre.1999.1925 PG 16 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 282MM UT WOS:000085222700013 PM 10617442 ER PT J AU Devasahayam, N Subramanian, S Murugesan, R Cook, JA Afeworki, M Tschudin, RG Mitchell, JB Krishna, MC AF Devasahayam, N Subramanian, S Murugesan, R Cook, JA Afeworki, M Tschudin, RG Mitchell, JB Krishna, MC TI Parallel coil resonators for time-domain radiofrequency electron paramagnetic resonance imaging of biological objects SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID PULSED MAGNETIC-RESONANCE; SPIN-RESONANCE; HIGH-RESOLUTION; LOW-FREQUENCY; FREE-RADICALS; EPR; SPECTROMETER; PROBE; SPECTROSCOPY; OXIMETRY AB Resonators suitable for time-domain electron paramagnetic resonance spectroscopy and imaging at a radiofrequency capable of accommodating experimental animals such as mice are described. Design considerations included B-1 field homogeneity, optimal Q, spectral bandwidth, resonator ring-down, and sensitivity. Typically, a resonator with 25-mm diameter and 25-mm length was constructed by coupling 11 single loops in parallel with a separation of 2.5 mm. To minimize the resonator ring-down time and provide the necessary spectral bandwidth for in vivo imaging experiments, the Q was reduced predominantly by overcoupling. Capacitative coupling was utilized to minimize microphonic effects. The B-1 field in the resonator was mapped both radially and axially and found to be uniform and adequate for imaging studies. Imaging studies with phantom objects containing a narrow-line spin probe as well as in vivo objects administered with the spin probe show the suitability of these resonators for valid reproduction of the spin probe distribution in three dimensions. The fabrication of such resonators is simple and can be scaled up with relative ease to accommodate larger objects as well. (C) 2000 Academic Press. C1 NCI, Div Clin Sci, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Devasahayam, N (reprint author), NCI, Div Clin Sci, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NR 33 TC 46 Z9 46 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2000 VL 142 IS 1 BP 168 EP 176 DI 10.1006/jmre.1999.1926 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 282MM UT WOS:000085222700019 PM 10617448 ER PT J AU Ishii, Y Tycko, R AF Ishii, Y Tycko, R TI Sensitivity enhancement in solid state N-15 NMR by indirect detection with high-speed magic angle spinning SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE solid state NMR; magic angle spinning; indirect detection; nitrogen-15 NMR; peptides ID DIPOLAR-CORRELATION SPECTROSCOPY; NUCLEAR-MAGNETIC-RESONANCE; ROTATING SOLIDS; SHIFT CORRELATION; QUANTUM NMR; COUPLINGS; PROTON; FIELD; HELIX; POLARIZATION AB Enhancement of sensitivity in solid state N-15 NMR by indirect detection through H-1 NMR signals under high-speed magic angle spinning and high-field conditions is demonstrated experimentally on two N-15-labeled peptides, polycrystalline AlaGlyGly and the helix-forming, 17-residue peptide MB(i + 4)EK in lyophilized form. Sensitivity enhancement factors ranging from 2.0 to 3.2 are observed experimentally, depending on the (1)5N and H-1 linewidths and polarization transfer efficiencies. The H-1-detected two-dimensional H-1/N-15 correlation spectrum of AlaGlyGly illustrates the possibility of increased spectral resolution and resonance assignments in indirectly detected experiments, in addition to the sensitivity enhancement. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Ishii, Y (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Ishii, Yoshitaka/F-4558-2014 OI Ishii, Yoshitaka/0000-0002-7724-6469 NR 41 TC 129 Z9 130 U1 7 U2 35 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2000 VL 142 IS 1 BP 199 EP 204 DI 10.1006/jmre.1999.1976 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 282MM UT WOS:000085222700024 PM 10617453 ER PT J AU Kramer, BS AF Kramer, BS TI Spiral computed tomography screening SO JOURNAL OF MEDICAL SCREENING LA English DT Editorial Material ID LUNG-CANCER C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Kramer, BS (reprint author), NCI, Div Canc Prevent, Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 2000 VL 7 IS 3 BP 121 EP 122 DI 10.1136/jms.7.3.121 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 381MP UT WOS:000165766900001 PM 11126157 ER PT J AU Tang, J Hu, M Lee, S Roblin, R AF Tang, J Hu, M Lee, S Roblin, R TI A polymerase chain reaction based method for detecting Mycoplama/Acholeplasma contaminants in cell culture SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Acholeplasma laidlawii; cell culture contaminants; Mycoplasma detection; polymerase chain reaction (PCR) ID PCR-BASED DETECTION; IDENTIFICATION; MYCOPLASMAS; SPACER AB a detection system that utilizes a primer mixture in a nested polymerase chain reaction for detecting Mycoplasma contaminants in cell cultures is described. Primers were designed to amplify the spacer regions between the 16S and 23S ribosomal RNA genes of Mycoplasma and Acholeplasma. This detection system was able to detect 20-180 colony forming units per milliliter of sample. Eight commonly encountered Mycoplasma and Acholeplasma contaminants, which include Mycoplasma (M.) arginini, M. fermentans, M. hominis, M. hyorhinis, M. orale, M. pirum, M. salivarium, and Acholeplasma laidlawii, were consistently amplified. Mycoplasma contaminants generated a single DNA band of 236-365 base pairs (bp), whereas A. laidlawii produced a characteristic two-band pattern of 426 and 219 bp amplicons. Species identification could be achieved by size determination and restriction enzyme digestion. Minor cross-reactions were noted with a few closely related gram positive bacteria and DNA from rat cell lines. A Mycoplasma Detection Kit for detecting Mycoplasma contaminants in cell cultures has been developed based on this approach. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Amer Type Culture Collect, Bacteriol Program, Manassas, VA 20110 USA. Pro Virus Inc, Gaithersburg, MD 20877 USA. NIH, Dept Cell & Canc Biol, Bethesda, MD 20892 USA. Point Care Technol, Rockville, MD 20850 USA. RP Tang, J (reprint author), Amer Type Culture Collect, Bacteriol Program, 10801 Univ Blvd, Manassas, VA 20110 USA. EM jtang@atcc.org NR 17 TC 52 Z9 55 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JAN PY 2000 VL 39 IS 2 BP 121 EP 126 DI 10.1016/S0167-7012(99)00107-4 PG 6 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 256DV UT WOS:000083711400003 PM 10576701 ER PT J AU Bichsel, VE Petricoin, EF Liotta, LA AF Bichsel, VE Petricoin, EF Liotta, LA TI The state of the art microdissection and its downstream applications SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article; Proceedings Paper CT EuroConference on Microdissection and its Downstream Tools CY SEP 15-17, 2000 CL BONN, GERMANY SP European Commiss ID LASER CAPTURE MICRODISSECTION C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 6 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PY 2000 VL 78 IS 7 BP B20 EP B20 PG 1 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 357CY UT WOS:000089482000006 PM 11043383 ER PT J AU Li, LP Pedersen, LG Beard, WA Bebenek, K Wilson, SH Kunkel, TA Darden, TA AF Li, LP Pedersen, LG Beard, WA Bebenek, K Wilson, SH Kunkel, TA Darden, TA TI A molecular dynamics model of HIV-1 reverse transcriptase complexed with DNA: Comparison with experimental structures SO JOURNAL OF MOLECULAR MODELING LA English DT Article DE HIV-1 reverse transcriptase; minor groove binding track; Particle-mesh Ewald ID IMMUNODEFICIENCY-VIRUS TYPE-1; ALANINE-SCANNING MUTAGENESIS; GROOVE BINDING TRACK; PARTICLE MESH EWALD; DOUBLE-STRANDED DNA; ANGSTROM RESOLUTION; NONNUCLEOSIDE INHIBITORS; CRYSTAL-STRUCTURE; TEMPLATE-PRIMER; THUMB SUBDOMAIN AB We have built a molecular dynamics model for human immunodeficiency virus (HIV-1) reverse transcriptase (RT) complexed with a 19/18-mer template/primer by combining the structural information of a low resolution crystal structure of a HIV-1 RT/DNA complex (1hmi) with that of a high resolution crystal structure of unliganded HIV-1 RT (1rtj). The process involved slow forcing of the alpha -carbons of 1rtj onto those of 1hmi using constrained MD simulations, while immersing the protein in aqueous solution. A similar technique was used to build the bent all-atom DNA duplex, which was then docked into the modeled protein. The resulting model complex was refined using molecular dynamics simulation with the Particle-mesh Ewald method employed to accommodate long-range electrostatic interactions. New parameters of the Amber force field that affect DNA twist are tested and largely validated. The model has been used successfully to explain the results of vertical scanning mutagenesis of residue 266 (Trp266). Recently, the low resolution crystal structure of the HIV-1 RT/DNA complex has been refined to a 2.8 Angstrom resolution (2hmi) and a crystal structure of a HIV-1/RT/dTTP ternary complex has been determined at 3.2 Angstrom resolution (1rtd). A detailed structural comparison of the prior model structure and the two experimental structures becomes possible. Overall, the three structures share many similarities. The root mean square deviations of the alpha -carbons for the individual subdomains among the three structures are within the same ranges. The secondary structure assignments in the three structures are nearly identical. Key protein-DNA contacts such as those in the region of the primer grip are also similar in the three structures. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC USA. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Darden, TA (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 37 TC 3 Z9 4 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0948-5023 J9 J MOL MODEL JI J. Mol. Model. PY 2000 VL 6 IS 10-11 BP 575 EP 586 DI 10.1007/s0089400060575 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Chemistry; Computer Science GA 382QP UT WOS:000165834000001 ER PT J AU Newman, JD AF Newman, JD TI Affective neuroscience: The foundations of human and animal emotions. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. RP Newman, JD (reprint author), NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 2000 VL 188 IS 1 BP 59 EP 59 DI 10.1097/00005053-200001000-00015 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 273WL UT WOS:000084732300014 ER PT J AU Nowak, G Li, Y Paul, IA AF Nowak, G Li, Y Paul, IA TI Chronic glycine treatment desensitizes the behavioral response to 1-aminocyclopropanecarboxylic acid (ACPC), a partial agonist at the strychnine-insensitive glycine site of the NMDA receptor complex SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE glycine; ACPC; NMDA receptor; forced swim test; mice ID EXHIBIT ANTIDEPRESSANT; ANIMAL-MODEL; ANTAGONISTS; DEPRESSION; ADAPTATION; POTENT; MK-801; IMIPRAMINE AB Chronic treatment with 1-aminocyclopropanecarboxylic acid (ACPC) but not with dizocilpine or imipramine produces desensitization to the behavioral response in ACPC challenge in the forced swim test (forced swim test). The mechanism by which ACPC produces this effect is unclear and may depend upon either its functional antagonist or its agonist properties at the NMDA receptor. We now report that chronic treatment with glycine or ACPC desensitizes the behavioral effect of challenge with ACPC in the forced swim test. The desensitization of the acute effects of ACPC cannot be explained by the presence of residual glycine because 24h after the last of 14 daily glycine injections (i.e. the time of forced swim test) cortical and hippocampal glycine concentrations were unchanged. Likewise, the affinity of glycine to displace specific [H-3]5,7-DCKA binding to glycine sites of the NMDA receptor complex was unchanged by chronic glycine administration. These results support the hypothesis that antidepressants produce adaptation of the NMDA receptor complex by mechanisms other than simply increasing synaptic glycine concentrations. Moreover, these results indicate that the behavioral adaptation in the forced swim test induced by chronic treatment with ACPC results from its agonist properties. C1 Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, DNBR,Lab Neurobehav Pharmacol & Immunol, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Dept Pharmacol, Jackson, MS 39216 USA. NIDDK, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Polish Acad Sci, Inst Pharmacol, Krakow, Poland. Jagiellonian Univ, Collegium Medicum, Lab Radioligand Res, Krakow, Poland. RP Paul, IA (reprint author), Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, DNBR,Lab Neurobehav Pharmacol & Immunol, 2500 N State St,Box 127, Jackson, MS 39216 USA. NR 27 TC 3 Z9 4 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PY 2000 VL 107 IS 2 BP 123 EP 131 DI 10.1007/s007020050011 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 282TM UT WOS:000085235000001 PM 10847554 ER PT J AU Kaelin-Lang, A Liniger, P Probst, A Lauterburg, T Burgunder, JM AF Kaelin-Lang, A Liniger, P Probst, A Lauterburg, T Burgunder, JM TI Adenosine A(2A) receptor gene expression in the normal striatum and after 6-OH-dopamine lesion SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE mouse; cat; human; rat; striatum; adenosine A(2A) receptors; 6-OH-dopamine ID H-3 CGS 21680; MESSENGER-RNA; RAT STRIATUM; MOLECULAR-CLONING; HUMAN BRAIN; NEURONS; COEXPRESSION; LOCALIZATION; GANGLIA AB Adenosine A(2A) receptors are present on enkephalinergic medium sized striatal neurons in the rat and have an important function in the modulation of striatal output. In order to establish more accurately whether adenosine transmission is a generalized phenomenon in mammalian striatum we compared the A(2A) R expression in the mouse, rat, cat and human striatum. Secondly we compared the modulation of enkephalin gene expression and A(2A) receptor gene expression in rat striatal neurons after 6-OH-dopamine lesion of the substantia nigra. Hybridization histochemistry was performed with a S-35-labelled radioactive oligonucleotide probe. The results showed high expression of A(2A) adenosine receptor genes only in the medium-sized cells of the striatum in all examined species. In the rat striatum, expression of A(2A) receptors was not significantly altered after lesion of the dopaminergic pathways with 6-OH-dopamine even though enkephalin gene expression was up-regulated. The absence of a change in A(2A) receptor gene expression after 6-OH-dopamine treatment speaks against a dependency on dopaminergic innervation. The maintained inhibitory function of A(2R) R on motor activity in spite of dopamine depletion could be partly responsible for the depression of locomotor activity observed in basal ganglia disorders such as Parkinson's disease. C1 Univ Hosp Bern, Inselspital, Dept Neurol, Neuromorphol Lab, CH-3010 Bern, Switzerland. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. RP Kaelin-Lang, A (reprint author), NINDS, NIH, Bldg 10,Room 5N234,10 Ctr Dr,MSC 1430, Bethesda, MD 20892 USA. NR 27 TC 23 Z9 23 U1 0 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PY 2000 VL 107 IS 8-9 BP 851 EP 859 DI 10.1007/s007020070037 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 347WG UT WOS:000088951700001 PM 11041267 ER PT J AU Kim, S Nelson, PG AF Kim, S Nelson, PG TI Involvement of calpains in the destabilization of the acetylcholine receptor clusters in rat myotubes SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE calpains; calpain inhibitor I; calpain inhibitor II; calpeptin; rat clusters ID DUCHENNE MUSCULAR-DYSTROPHY; UTROPHIN-DEFICIENT MICE; CULTURED MUSCLE-CELLS; NEUROMUSCULAR-JUNCTIONS; SKELETAL-MUSCLE; PROTEASE INHIBITORS; NEUTRAL PROTEASE; BETA-SPECTRIN; PHORBOL ESTER; CALCIUM AB The effects of calpain inhibitors on the total number of acetylcholine receptors (AChRs) on cultured rat myotubes and on the stability of AChR clusters in these myotubes were investigated. The degradation rate of total AChRs labeled with I-125-alpha-bungarotoxin was assessed from radioactivity remaining in the myotubes as a function of time, Treatment with calpain inhibitors resulted in a two- to three-fold increase in the half-life of total AChRs. Incubation with these inhibitors produced 40% increases in intracellular AChRs but no major changes in surface AChRs, indicating that the increased AChR half-life is due to intracellular accumulation, The rate loss of AChRs from the clusters was assessed by measuring the loss of fluorescence intensity in rhodaminated-alpha-bungarotoxin-labeled clusters with time. Treatment with calpain inhibitors resulted in two-fold increases in cluster half-life. Thus, there was generally no change in total surface receptors with the calpain inhibitors, whereas cluster half-life was substantially increased. Furthermore, with a low dose of calpeptin there was no change in turnover of total cellular AChRs, whereas cluster half-life was doubted, Taken together, these results suggest that the increased half-life of clusters produced by the calpain inhibitors may be due to retardation of the lateral movement from AChRs in the clusters. (C) 2000 John Wiley & Sons, Inc.* C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, S (reprint author), NICHHD, Dev Neurobiol Lab, NIH, Bldg 49,Rm 5A 38,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 48 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD JAN PY 2000 VL 42 IS 1 BP 22 EP 32 DI 10.1002/(SICI)1097-4695(200001)42:1<22::AID-NEU3>3.0.CO;2-# PG 11 WC Neurosciences SC Neurosciences & Neurology GA 266PX UT WOS:000084309300003 PM 10623898 ER PT J AU Walcourt, A Nash, HA AF Walcourt, A Nash, HA TI Genetic effects on an anesthetic-sensitive pathway in the brain of Drosophila SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE general anesthesia; halothane; mushroom body; escape response; Drosophila melanogaster ID CAENORHABDITIS-ELEGANS; VOLATILE ANESTHETICS; GENERAL-ANESTHETICS; SHAKER MUTANT; MELANOGASTER; MUTATIONS; POTASSIUM; FLIGHT AB General anesthetics are known to inhibit the electrically induced escape response of the fruitfly through action within the brain. We examined this response and its sensitivity to anesthetics in several mutants that cause significant disruption of the mushroom body and other structures of the central brain in adult flies. Because we show here that anesthesia sensitivity is influenced by genetic background, we have used a set of congenic mutant lines. Sensitivity to halothane is normal in most of these lines, indicating that the anesthetic target is unaffected by the gross status of the central brain. Thus, for the escape response, anesthetic sensitivity is not a global feature but reflects action at a localized target. Only the mushroom body defect (mud) line showed an increased sensitivity of the escape response to halothane, Sensitivity to tno other anesthetics is also perturbed in this line, albeit less dramatically so. The behavior of mud/+ heterozygotes and the comparison of brain anatomy among all the mutant lines imply that the effect of the mud mutation on anesthesia is not via gross alteration of central brain structures. The possibility that an adventitious mutation in the mud line is responsible for the effects on anesthesia is disfavored by the behavior of a heterozygote between two mud alleles. Although we do not yet know whether the mud gene encodes an anesthetic target or influences the functioning of an anesthetic-sensitive neuron in this pathway, our work indicates that this gene regulates the effects of halothane on a circumscribed pathway. (C) 2000 John Wiley & Sons, Inc.* C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Nash, HA (reprint author), NIMH, Mol Biol Lab, Bldg 36,Room 1B08, Bethesda, MD 20892 USA. NR 34 TC 11 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD JAN PY 2000 VL 42 IS 1 BP 69 EP 78 DI 10.1002/(SICI)1097-4695(200001)42:1<69::AID-NEU7>3.3.CO;2-R PG 10 WC Neurosciences SC Neurosciences & Neurology GA 266PX UT WOS:000084309300007 PM 10623902 ER PT J AU Hashimoto, K Guroff, G Katagiri, Y AF Hashimoto, K Guroff, G Katagiri, Y TI Delayed and sustained activation of p42/p44 mitogen-activated protein kinase induced by proteasome inhibitors through p21(ras) in PC12 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE proteasome; signal transduction; mitogen-activated protein kinase; nerve growth factor; PC12 cells ID NERVE GROWTH-FACTOR; SIGNAL-REGULATED KINASE; CELL-CYCLE ARREST; MAP-KINASE; NEURITE OUTGROWTH; NEUROBLASTOMA-CELLS; PC-12 CELLS; LACTACYSTIN; INDUCTION; DIFFERENTIATION AB Proteolysis by the ubiquitin/proteasome pathway regulates the intracellular level of several proteins, some of which control cell proliferation and cell cycle progression. To determine what kinds of signaling cascades are activated or inhibited by proteasome inhibition, we treated PC12 cells with specific proteasome inhibitors and subsequently performed in-gel kinase assays. N-Acetyl-Leu-Leu-norleucinal and lactacystin, which inhibit the activity of the proteasome, induced the activation of p42/p44 mitogen-activated protein (MAP) kinases [extracellular signal-regulated kinases (ERKs) 1 and 2], In contrast, N-acetyl-Leu-Leu-methional, which inhibits the activity of calpains, but not of the proteasome, failed to induce ERK activation. Uniquely, the kinetics of MAP kinase activation induced by proteasome inhibitors are very slow compared with those resulting from activation by nerve growth factor; ERK activation is detectable only after a 5-h treatment with the inhibitors, and its activity remained unchanged for at least until 27 h. Proteasome inhibitor-initiated ERK activation is inhibited by pretreatment with the ERK kinase inhibitor PD 98059, as well as by overexpression of a dominant-negative form of Pas. Thus, proteasome inhibitors induce sustained ERK activation in a Pas-dependent manner. Proteasome inhibitor-induced neurite outgrowth, however, is not inhibited by PD 98059, indicating that sustained activation of ERKs is not the factor responsible for proteasome inhibitor-induced morphological differentiation. Our data suggest the presence of a novel mechanism for activation of the MAP kinase cascade that involves proteasome activity. C1 NICHHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. RP Katagiri, Y (reprint author), NICHHD, Growth Factors Sect, NIH, Bldg 49,Room 5A51,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2000 VL 74 IS 1 BP 92 EP 98 DI 10.1046/j.1471-4159.2000.0740092.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 266HM UT WOS:000084294600009 PM 10617109 ER PT J AU Camandola, S Poli, G Mattson, MP AF Camandola, S Poli, G Mattson, MP TI The lipid peroxidation product 4-hydroxy-2,3-nonenal increases AP-1-binding activity through caspase activation in neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; hippocampus; 4-hydroxy-2,3-nonenal; c-Jun N-terminal kinase; neurons; transcription factor ID AMYLOID BETA-PEPTIDE; MITOCHONDRIAL PERMEABILITY TRANSITION; AMYOTROPHIC-LATERAL-SCLEROSIS; JUN NH2-TERMINAL KINASE; PROGRAMMED CELL-DEATH; MANGANESE SUPEROXIDE-DISMUTASE; DRUG-INDUCED APOPTOSIS; DNA-BINDING ACTIVITY; C-FOS PROTOONCOGENE; TRANSCRIPTION FACTOR AB The transcription factor activator protein-1 (AP-1) is activated in response to physiological activity in neuronal circuits and in response to neuronal injury associated with various acute and chronic neurodegenerative conditions. The membrane lipid peroxidation product 4-hydroxy-2,3-nonenal (HNE) is increasingly implicated in the disruption of neuronal calcium homeostasis that occurs in various paradigms of neuronal excitotoxicity and apoptosis. The possible mechanistic links between lipid peroxidation and alterations in gene transcription during neuronal apoptosis have not previously been examined. We now report that exposure of cultured rat cortical neurons to an apoptotic concentration of HNE results in a large increase in AP-I DNA-binding activity. The protein synthesis inhibitor cycloheximide blocked the induction of AP-1, consistent with a requirement for induction of expression of AP-I family members. The broad-spectrum caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone and the caspase-3 inhibitor N-acetyl-Asp-Glu-Val-Asp-aldehyde blocked HNE-induced increases in AP-I DNA-binding activity, demonstrating a requirement for caspase activation in the activation of AP-1, HNE induced phosphorylation of c-Jun N-terminal kinase (JNK), which was prevented by caspase inhibitors, indicating that HNE was acting at or upstream of JNK phosphorylation. The intracellular calcium chelator BAPTA-acetoxymethyl ester completely prevented stimulation of AP-1 DNA-binding by HNE, indicating a requirement for calcium. Moreover, agents that suppress mitochondrial calcium uptake (ruthenium red) and membrane permeability transition (cyclosporin A) attenuated AP-1 activation by HNE, suggesting a contribution of mitochondrial alterations to AP-I activation, Collectively, our data suggest a scenario in which HNE disrupts neuronal calcium homeostasis and perturbs mitochondrial function, resulting in caspase activation. Activated caspases, in turn, induce activation of JNK, resulting in stimulation of AP-I DNA-binding protein production. This transcriptional pathway induced by HNE may modulate the cell death process. C1 Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Univ Turin, SL Gonzaga Hosp, Dept Clin & Biol Sci, Orbassano, Italy. RP Mattson, MP (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 97 TC 130 Z9 143 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2000 VL 74 IS 1 BP 159 EP 168 DI 10.1046/j.1471-4159.2000.0740159.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 266HM UT WOS:000084294600017 PM 10617117 ER PT J AU Xiao, DM Pak, JH Wang, XM Sato, T Huang, FL Chen, HC Huang, KP AF Xiao, DM Pak, JH Wang, XM Sato, T Huang, FL Chen, HC Huang, KP TI Phosphorylation of HMG-I by protein kinase C attenuates its binding affinity to the promoter regions of protein kinase C gamma and neurogranin/RC3 genes SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE protein kinase C gamma; neurogranin/RC3; chromosomal nonhistone high-mobility-group; protein-I; phosphorylation; DNA-binding protein ID MOBILITY-GROUP PROTEINS; IMMUNOCYTOCHEMICAL LOCALIZATION; CDC2 KINASE; RAT-BRAIN; CELLS; IDENTIFICATION; CHROMATIN; ISOZYMES; PURIFICATION; EXPRESSION AB A 20-kDa DNA-binding protein that binds the AT-rich sequences within the promoters of the brain-specific protein kinase C (PKC) gamma and neurogranin/RC3 genes has been characterized as chromosomal nonhistone high-mobility-group protein (HMG)-I, This protein is a substrate of PKC alpha, beta, gamma, and delta but is poorly phosphorylated by PKC epsilon and zeta. Two major (Ser(44) and Ser(64)) and four minor phosphorylation sites have been identified. The extents of phosphorylation of Ser(44) and Ser(64) were 1:1, whereas those of the four minor sites all together were <30% of the major one. These PKC phosphorylation sites are distinct from those phosphorylated by cdc2 kinase, which phosphorylates Thr(53) and Thr(78). Phosphorylation of HMG-I by PKC resulted in a reduction of DNA-binding affinity by 28-fold as compared with 12-fold caused by the phosphorylation with cdc2 kinase, HMG-I could be additively phosphorylated by cdc2 kinase and PKC, and the resulting doubly phosphorylated protein exhibited a >100-fold reduction in binding affinity. The two cdc2 kinase phosphorylation sites of HMG-I are adjacent to the N terminus of two of the three predicted DNA-binding domains. In comparison, one of the major PKC phosphorylation sites, Ser(64), is adjacent to the C terminus of the second DNA-binding domain, whereas Ser(44) is located within the spanning region between the first and second DNA-binding domains. The current results suggest that phosphorylation of the mammalian HMG-I by PKC alone or in combination with cdc2 kinase provides an effective mechanism for the regulation of HMG-I function. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A36,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. EM kphuang@helix.nih.gov NR 26 TC 45 Z9 46 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 2000 VL 74 IS 1 BP 392 EP 399 DI 10.1046/j.1471-4159.2000.0740392.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 266HM UT WOS:000084294600044 PM 10617144 ER PT J AU Ahmad, A Greiner, RS Moriguchi, T Salem, N AF Ahmad, A Greiner, RS Moriguchi, T Salem, N TI Effects of dietary omega-3 fatty acid on the morphology of the hippocampus SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S88 EP S88 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200350 ER PT J AU Akbar, M Kim, HY AF Akbar, M Kim, HY TI Protective effect of docosahexaenoic acid in neuronal apoptosis: Involvement of phosphatidyl inositol 3-kinase pathway SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIAAA, Sect Mass Spectrometry, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S7 EP S7 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200026 ER PT J AU Bridgman, PC Tullio, AN Wei, Q Adelstein, RS AF Bridgman, PC Tullio, AN Wei, Q Adelstein, RS TI Myosin IIB regulates growth cone motility and actin organization. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NHLBI, NIH, Mol Cardiol Lab, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S91 EP S91 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200365 ER PT J AU Chan, SL Lee, J Kruman, Y Mattson, MP AF Chan, SL Lee, J Kruman, Y Mattson, MP TI Evidence that upregulation of presenilins in primary neurons during metabolic stress is neuroprotective. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S6 EP S6 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200025 ER PT J AU Cohen, RI Maric, D Barker, J Hudson, LD AF Cohen, RI Maric, D Barker, J Hudson, LD TI In vivo and in vitro microarray analysis of developing oligodendroglia. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, LDN, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S91 EP S91 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200364 ER PT J AU Contreras, MA Greiner, RS Chang, MCJ Myers, CS Bell, JM Balbo, A Salem, N Rapoport, SL AF Contreras, MA Greiner, RS Chang, MCJ Myers, CS Bell, JM Balbo, A Salem, N Rapoport, SL TI Chronic deprivation of alpha-linolenic acid decreases the turnover of docosahexaenoate in rats brain phospholipids. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NIAAA, LMBB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S88 EP S88 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200352 ER PT J AU Culmsee, C Monnig, J Kemp, BE Mattson, MP AF Culmsee, C Monnig, J Kemp, BE Mattson, MP TI Evidence that AMP activated protein kinase protects against metabolic, excitotoxic and oxidative insults in embryonic hippocampal neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. St Vincents Hosp, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. RI Mattson, Mark/F-6038-2012; Kemp, Bruce/L-2633-2014 OI Kemp, Bruce/0000-0001-6735-5082 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S74 EP S74 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200296 ER PT J AU Dashiell, SM Tanner, SL Pant, HC Quarles, RH AF Dashiell, SM Tanner, SL Pant, HC Quarles, RH TI Myelin-associated glycoprotein modulates expression and phosphorylation of neuronal cytoskeletal elements and their associated kinases in vitro and in vivo. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S45 EP S45 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200178 ER PT J AU Fields, RD AF Fields, RD TI Regulation of schwann cell proliferation by action potentials in premyelinated axons. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S54 EP S54 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200215 ER PT J AU Gallo, V Ghiani, CA Heckman, T McBain, CJ AF Gallo, V Ghiani, CA Heckman, T McBain, CJ TI Neurotransmittter receptors and ionic channels regulate cell cycle progression in oligodendrocyte progenitor cells. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S54 EP S54 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200214 ER PT J AU Ginis, I Liu, J Spatz, M Hallenbeck, JM Shohami, E AF Ginis, I Liu, J Spatz, M Hallenbeck, JM Shohami, E TI Tumor necrosis factor and reactive oxygen species cooperative cytotoxicity is mediated via inhibition of NF kB. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91120 Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S7 EP S7 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200029 ER PT J AU Gioio, AE Zhang, HS Wen, H Guiditta, A Kaplan, BB AF Gioio, AE Zhang, HS Wen, H Guiditta, A Kaplan, BB TI Differential mrna display: Identification of the constituents of a diverse population of mrnas in the axon and presynaptic nerve terminal. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Naples, Dept Gen Physiol, Naples, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S91 EP S91 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200362 ER PT J AU Haughey, NJ Mattson, MP Nath, A Hochman, S Geiger, JD AF Haughey, NJ Mattson, MP Nath, A Hochman, S Geiger, JD TI Facilitation of NMDA-mediated calcium flux by the HIV-1 protein Tat involves tyrosine kinase-dependent modulation of the zinc site an NMDA receptors. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. Emory Univ, Dept Physiol, Atlanta, GA 30322 USA. Univ Manitoba, Dept Pharmacol, Winnipeg, MB, Canada. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S19 EP S19 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200074 ER PT J AU Itoh, Y Gotoh, J Kuang, TY Cook, M Law, MJ Sokoloff, L AF Itoh, Y Gotoh, J Kuang, TY Cook, M Law, MJ Sokoloff, L TI No evidence for glucose-6-phosphatase activity in cultured astroglia. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIHM, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S81 EP S81 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200325 ER PT J AU Kruman, II Chan, SL Kruman, Y Penix, L Mattson, MP AF Kruman, II Chan, SL Kruman, Y Penix, L Mattson, MP TI Disturbance of endoplasmic reticulum function accompanies neurotoxicity of homocysteine SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S74 EP S74 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200297 ER PT J AU Lee, J Duan, W Herman, JP Mattson, MP AF Lee, J Duan, W Herman, JP Mattson, MP TI Neuroprotective effect of dietary restriction involves a stress response and increased expression of neurotrophic factors. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013; Herman, James/D-4960-2015 OI Herman, James/0000-0003-3571-2406 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S18 EP S18 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200073 ER PT J AU Lu, C Chan, SL Mattson, MP AF Lu, C Chan, SL Mattson, MP TI The lipid peroxidation product 4-hydroxynonenal enhances voltage-dependent calcium current AMPA- and NMDA-induced currents in hippocampal neurons. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S66 EP S66 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200263 ER PT J AU Mattson, MP Camandola, S Culmsee, C Yu, ZF AF Mattson, MP Camandola, S Culmsee, C Yu, ZF TI Elucidating the roles of NF-kappa B in neuronal plasticity and neurodegenerative disorders. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S51 EP S51 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200204 ER PT J AU Mattson, MP Partin, J AF Mattson, MP Partin, J TI Control of neuronal polarity by calcium and mitochondria. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S1 EP S1 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200005 ER PT J AU Mezey, E Chandross, KJ Harta, G Maki, RA McKercher, SR AF Mezey, E Chandross, KJ Harta, G Maki, RA McKercher, SR TI Hematopoietic cells give rise to neural cells in the brain. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. Burnham Inst, La Jolla, CA 92037 USA. Neurocrine Biosci, San Diego, CA 92121 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S40 EP S40 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200161 ER PT J AU Murphy, EJ Shapiro, MB Rapoport, SI Shetty, HU AF Murphy, EJ Shapiro, MB Rapoport, SI Shetty, HU TI Phospholipid composition and levels are altered in Down Syndrome brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, SBPM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S88 EP S88 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200353 ER PT J AU Murphy, EJ AF Murphy, EJ TI Plasmalogens and lipid-mediated signal transduction: Compatibility in the central nervous system? SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, SBPM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S55 EP S55 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200220 ER PT J AU Ohara, Y McCarron, RM Hoffman, T Chen, Y Lenz, FA Spatz, M AF Ohara, Y McCarron, RM Hoffman, T Chen, Y Lenz, FA Spatz, M TI Modulation of TNF alpha-stimulated ICAM-1 expression on human brain microvascular endothelial cells by isoproterenol. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 JHU, Sch Med, Dept Neurosurg, Baltimore, MD USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S71 EP S71 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200284 ER PT J AU Patrick, CB Rapoport, SI Murphy, EJ AF Patrick, CB Rapoport, SI Murphy, EJ TI A fluormetric method to measure 85 kDa phospholipase A(2) (type IV) in brain cytosol SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Cumberland Coll, Dept Biol, Williamsburg, KY USA. NIA, SBPM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S89 EP S89 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200356 ER PT J AU Patrick, CB Ramassamy, C Krzywkowski, P Poirier, J Rapoport, SI Murphy, EJ AF Patrick, CB Ramassamy, C Krzywkowski, P Poirier, J Rapoport, SI Murphy, EJ TI Phospholipase A(2) activity is decreased in the hippocampus of Apo E deficient mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Cumberland Coll, Dept Biol, Williamsburg, KY USA. Douglas Hosp, Res Ctr, Verdun, PQ H4H 1R3, Canada. NIA, SBPM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S89 EP S89 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200354 ER PT J AU Rapoport, SI Chang, MC Connolly, K Kessler, D Bokde, A Carson, RE Herscovitch, P Channing, M Eckelman, WC AF Rapoport, SI Chang, MC Connolly, K Kessler, D Bokde, A Carson, RE Herscovitch, P Channing, M Eckelman, WC TI In vivo imaging of phospholipase A(2)-mediated signaling in human brain using [C-11]arachidonic acid and positron emission tomography (PET) SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Sect Brain Physiol Metab, Bethesda, MD 20892 USA. NIH, PET Dept, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S21 EP S21 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200083 ER PT J AU Rosenberger, TA Rapoport, SI Murphy, EJ AF Rosenberger, TA Rapoport, SI Murphy, EJ TI Heterogeneous synthesis and distribution of ether phospholipids in the adult rat brain. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S88 EP S88 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200351 ER PT J AU Stevens, B Fields, RD AF Stevens, B Fields, RD TI Activity-dependent release of ATP from DRG axons regulates Schwann cell differentiation and development. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S82 EP S82 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200326 ER PT J AU Weiss, MD Haminer, JA Quarles, RH AF Weiss, MD Haminer, JA Quarles, RH TI Biochemical changes in the brains of aging mice lacking the myelin-associated glycoprotein (MAG) are indicative of an oligodendrogliopathy SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, Myelin & Brain Dev Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 2000 VL 74 SU S BP S33 EP S33 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 285DB UT WOS:000085373200133 ER PT J AU Tao-Cheng, JH Du, J McBain, CJ AF Tao-Cheng, JH Du, J McBain, CJ TI Snap-25 is polarized to axons and abundant along the axolemma: an immunogold study of intact neurons SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID PERIPHERAL NERVOUS-SYSTEM; DENSE-CORED VESICLES; CELLS; SYNTAXIN-1; EXOCYTOSIS; ORGANELLES; TERMINALS; MEMBRANES; PROTEINS; COMPLEX AB SNAP-25, synaptosomal associated protein of 25 kDa, is reported to be a t-SNARE (target receptor associated with the presynaptic plasma membrane) involved in the docking and fusion of synaptic vesicles. We present here the first ultrastructural localization of SNAP-25 in intact neurons by pre-embedding EM immunocytochemistry in rat brains, hippocampal slice cultures, and PC12 cells. In differentiated neurons, SNAP-25 labeling was clearly membrane-associated. The labeling was most prominent in the plasma membrane of axons and excluded from the plasma membranes of soma and dendrites. Furthermore, SNAP-25 did not appear to be restricted to the synaptic junctions. SNAP-25 labeling was seen in the cytoplasm of the soma and large dendrites, mostly associated with the Golgi complexes. There were also some SNAP-25 labeled tubulo-vesicular structures in the cytoplasm of the soma and the axons, but rarely in the smaller dendrites. In PC12 cells, after 5-10 minutes of high potassium (75 mM) stimulation in the presence of HRP, SNAP-25 labeling appeared, additionally, on HRP-filled early endosomes. After a longer (20-30 minutes) HRP incubation, most of the later stage endosomes and lysosomes were loaded with HRP but they were negative for SNAP-25. These results suggest that SNAP-25 is sorted out of these late endosomal compartments, and that the bulk of the SNAP-25 protein is probably recycled back to the axolemma from the early endosomes. In contrast, in those samples which were incubated with HRP for longer periods, there were still some SNAP-25-positive vesicular structures which were HRP-negative. These structures most likely represent anterograde vesicles that carry newly synthesized SNAP-25 from the soma to the axolemma by axonal transport. SNAP-25 appears to be sorted at the Golgi complex to reach the axolemma specifically. Its widespread distribution all along the axolemma does not support the view of SNAP-25 as a t-SNARE limited for synaptic exocytosis. C1 NINDS, EM Facil, NIH, Bethesda, MD 20892 USA. NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Tao-Cheng, JH (reprint author), NINDS, EM Facil, NIH, Bethesda, MD 20892 USA. RI Du, Jing/A-9023-2012 NR 23 TC 38 Z9 39 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD JAN PY 2000 VL 29 IS 1 BP 67 EP 77 DI 10.1023/A:1007168231323 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 371AU UT WOS:000165156100006 PM 11068335 ER PT J AU Guan, ZH Scott, RL Nash, HA AF Guan, ZH Scott, RL Nash, HA TI A new assay for the genetic study of general anesthesia in Drosophila melanogaster: Use in analysis of mutations in the X-chromosomal 12E region SO JOURNAL OF NEUROGENETICS LA English DT Article DE halothane; mushroom body; dose-response curve; behavioral assay; genetic mapping ID MUTANTS; SENSITIVITY; HALOTHANE; ENCODES AB We describe a new measure of the influence of general anesthetics on Drosophila that uses the robust tendency of fruit flies to briskly walk upwards after being tapped down. We expose flies to a fixed concentration of anesthetic gas in a 50 ml tube for a period of up to Ih and then test the distribution of flies in the tube shortly after tapping them to its bottom. By measuring the effect of a series of anesthetic concentrations on the fraction of flies that fail to climb, we derive quantitative descriptors of the potency of the drug. This "distribution test" is superior to previous assays of anesthetic potency in terms of ease and reliability. We have used the assay to further the genetic analysis of several mutations that cluster on the X chromosome and are known to influence both neural function and anesthesia sensitivity. The results establish complementation patterns between the mutations, refine their genetic map positions, and open the way for the molecular identification of the relevant gene(s). C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Nash, HA (reprint author), NIMH, Mol Biol Lab, Bldg 36,Room 1B08, Bethesda, MD 20892 USA. NR 29 TC 22 Z9 23 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 0167-7063 J9 J NEUROGENET JI J. Neurogenet. PY 2000 VL 14 IS 1 BP 25 EP 42 DI 10.3109/01677060009083475 PG 18 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA 333MD UT WOS:000088133100002 PM 10938546 ER PT J AU Pau, A Dorcaratto, A Viale, GL Castellani, P Siri, A Zardi, L AF Pau, A Dorcaratto, A Viale, GL Castellani, P Siri, A Zardi, L TI Oncofetal matrix glycoproteins in cerebral arteriovenous malformations and neighbouring vessels SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Letter ID ED-B C1 Univ Genoa, Sch Med, Div Neurosurg, Dept Surg,S Martino Hosp, I-16132 Genoa, Italy. Natl Canc Inst, Cell Biol Lab, Genoa, Italy. RP Pau, A (reprint author), Univ Genoa, Sch Med, Div Neurosurg, Dept Surg,S Martino Hosp, Pad 2,Largo Rosanna Benzi 10, I-16132 Genoa, Italy. NR 5 TC 3 Z9 3 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JAN PY 2000 VL 68 IS 1 BP 101 EP 102 DI 10.1136/jnnp.68.1.101 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 270AL UT WOS:000084513200028 PM 10671114 ER PT J AU Miyake, K Kimura, S Nakanishi, M Hisada, A Hasegawa, M Nagao, S Abe, Y AF Miyake, K Kimura, S Nakanishi, M Hisada, A Hasegawa, M Nagao, S Abe, Y TI Transforming growth factor-beta 1 stimulates contraction of human glioblastoma cell-mediated collagen lattice through enhanced alpha 2 integrin expression SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE extracellular matrix; glioblastoma; HVJ-liposome; integrin; TGF-beta 1 ID MESSENGER-RNA EXPRESSION; EXTRACELLULAR-MATRIX; FACTOR-BETA; GLIOMA-CELLS; TUMOR PROGRESSION; GEL CONTRACTION; GENE-EXPRESSION; HUMAN BRAIN; IN-VITRO; FIBROBLASTS AB Rapid invasiveness is a feature of the highly malignant glioblastoma tumor and is closely related to patient prognosis. The interaction between extracellular matrix (ECM) and cell surface receptors such as integrin heterodimers play a key role in the process of tumor invasion. We investigated the effects of transforming growth factor-beta (TGF-beta 1), which is a mitogenic factor for glial cells. on integrin expression in T98G human glioblastoma cells using an in vitro model 3-dimensional collagen lattice. Exogenously applied TGF-beta 1 dose-dependently enhanced collagen lattice contraction. Among the inhibitory antibodies tested against alpha integrin subunits, the anti-alpha 2 antibody, P1-E6, alone prevented the enhanced contractile response by TGF-beta 1, whereas any alpha integrin antibody (including P1-E6) had little effect on lattice contraction when cultured without TGF-beta 1. RT-PCR analysis revealed that TGF-beta 1 strongly increased alpha 2, integrin transcript level. Furthermore, pretreatment with antisense phosphorothioate oligodeoxynucleotides against human alpha 2 integrin using hemagglutinating virus of Japan (HVJ) liposome-mediated transfer prevented the effects of TGF-beta 1 and also reduced the lattice contraction even in the absence of TGF-beta 1. This data indicates that increased expression of alpha 2 integrin is responsive to enhanced collagen lattice contraction by TGF-beta 1. We suggest that TGF-beta 1 exerts its effects on the invasive property of glioblastoma cells via upregulation of the alpha 2 integrin subunit expression. C1 NCI, Med Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. DNA VEC Res Inc, Ibaraki, Osaka, Japan. Osaka Univ, Microbial Dis Res Inst, Osaka, Japan. Osaka Univ, Microbial Dis Res Inst, Osaka, Japan. Kagawa Med Univ, Dept Neurol Surg, Kagawa, Japan. Kagawa Med Univ, Dept Pharmacol, Kagawa, Japan. RP Miyake, K (reprint author), NCI, Med Branch, Natl Inst Hlth, Bldg 10,Rm 12N-200,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 58 TC 18 Z9 18 U1 0 U2 2 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JAN PY 2000 VL 59 IS 1 BP 18 EP 28 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 279FL UT WOS:000085033700003 PM 10744032 ER PT J AU Stanley, EF AF Stanley, EF TI Presynaptic calcium channels and the depletion of synaptic cleft calcium ions SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CHICK CILIARY GANGLION; TRANSMITTER RELEASE; NEURONS; INACTIVATION; CURRENTS; CA2+; FACE AB The entry of calcium ions (Ca2+) through voltage-gated calcium channels is an essential step in the release of neurotransmitter at the presynaptic nerve terminal. Because the calcium channels are clustered at the release sites, the flux of Ca2+ into the terminal inevitably removes the ion from the adjacent extracellular space, the synaptic cleft. We have used the large calyx-type synapse of the chick ciliary ganglion to test for synaptic cleft Ca2+ depletion. The terminal was voltage clamped at a holding potential (V-H) of -80 mV and a depolarizing pulse was applied to a range of potentials (-60 to +60 mV). The voltage pulse activated a sustained inward calcium current and was followed, on return of the membrane potential to V-H by an inward calcium tail current. The amplitude of the tail current reflects both the number of open calcium channels at the end of the voltage pulse and the Ca2+ electrochemical gradient. External barium was substituted for calcium as the charge-carrying ion because initial experiments demonstrated calcium-dependent inactivation of the presynaptic calcium channels. Tail current recruitment was compared in calyx nerve terminals that remained attached to the postsynaptic neuron and therefore retained a synaptic cleft, with terminals that had been fully isolated. in isolated terminals, the tail currents exhibited recruitment curves that could be fit by a Boltzmann distribution with a mean V-1/2 of 0.4 mV and a slope factor of 5.4. However, in attached calyces tail current recruitment was skewed to depolarized potentials with a mean V-1/2 of 11.9 mV and a slope factor of 12.0. The degree of skew of the recruitment curve in the attached calyces correlated with the amplitude of the inward current evoked by the step depolarization. The simplest interpretation of these findings is that during the depolarizing pulse Ba2+ is removed from the synaptic cleft faster than it is replenished, thus reducing the tail current by reducing the driving force for ion entry. Ca2+ depletion during presynaptic calcium channel activation is likely to be a general property of chemical transmission at fast synapses that sets a functional limit to the duration of sustained secretion. The synapse may have evolved to minimized cleft depletion by developing a calcium-efficient mechanism to gate transmitter release that requires the concurrent opening of only a few low conductance calcium channels. C1 NINDS, Synapt Mech Sect, Bethesda, MD 20892 USA. RP Stanley, EF (reprint author), Toronto Western Res Inst, Div Cell & Mol Biol, Main Pavil 14-320,399 Bathurst St, Toronto, ON M5T 2S8, Canada. NR 22 TC 38 Z9 49 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2000 VL 83 IS 1 BP 477 EP 482 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 274RA UT WOS:000084777800043 PM 10634889 ER PT J AU Smith, GD Cox, CL Sherman, SM Rinzel, J AF Smith, GD Cox, CL Sherman, SM Rinzel, J TI Fourier analysis of sinusoidally driven thalamocortical relay neurons and a minimal integrate-and-fire-or-burst model SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATERAL GENICULATE-NUCLEUS; METABOTROPIC GLUTAMATE RECEPTORS; ACTIVATED CATION CURRENT; PIG THALAMIC NEURONS; ELECTROPHYSIOLOGICAL PROPERTIES; IN-VIVO; SPIKE; OSCILLATIONS; MECHANISMS; DYNAMICS AB We performed intracellular recordings of relay neurons from the lateral geniculate nucleus of a cat thalamic slice preparation. We measured responses during both tonic and burst firing modes to sinusoidal current injection and performed Fourier analysis on these responses. For comparison. we constructed a minimal "integrate-and-fire-or-burst" (IFB) neuron model that reproduces salient features of the relay cell responses. The IFB model is constrained to quantitatively fit our Fourier analysis of experimental relay neuron responses, including: the temporal tuning of the response in both tonic and burst modes, including a finding of low-pass and sometimes broadband behavior of tonic firing and band-pass characteristics during bursting, and the generally greater linearity of tonic compared with burst responses at low frequencies. In tonic mode, both experimental and theoretical responses display a frequency-dependent transition from massively superharmonic spiking to phase-locked superharmonic spiking near 3 Hz, followed by phase-locked subharmonic spiking at higher frequencies. Subharmonic and superharmonic burst responses also were observed experimentally. Characterizing the response properties of the "tuned" IFB model leads to insights regarding the observed stimulus dependence of burst versus tonic response mode in relay neurons. Furthermore the simplicity of the IFB model makes it a candidate for large scale network simulations of thalamic functioning. C1 SUNY Stony Brook, Dept Neurobiol, Stony Brook, NY 11794 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. NYU, Courant Inst Math Sci, New York, NY 10003 USA. NIDDK, Math Res Branch, NIH, Bethesda, MD 20814 USA. RP Sherman, SM (reprint author), SUNY Stony Brook, Dept Neurobiol, Stony Brook, NY 11794 USA. FU NEI NIH HHS [EY-03038, EY-06903-01] NR 36 TC 106 Z9 107 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2000 VL 83 IS 1 BP 588 EP 610 PG 23 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 274RA UT WOS:000084777800051 PM 10634897 ER PT J AU Ferraina, S Pare, M Wurtz, RH AF Ferraina, S Pare, M Wurtz, RH TI Disparity sensitivity of frontal eye field neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SUPERIOR COLLICULUS; FUNCTIONAL-PROPERTIES; RHESUS-MONKEY; VISUAL-CORTEX; VERGENCE; MOVEMENTS; AREA; CONVERGENCE; MECHANISMS; MIDBRAIN AB Information about depth is necessary to generate saccades to visual stimuli located in three-dimensional space. To determine whether monkey frontal eye field (FEF) neurons play a role in the visuo-motor processes underlying this behavior, we studied their visual responses to stimuli at different disparities. Disparity sensitivity was tested from 3 degrees of crossed disparity (near) to 3 degrees degrees of uncrossed disparity (far). The responses of about two thirds of FEF visual and visuo-movement neurons were sensitive to disparity and showed a broad tuning in depth for near or far disparities. Early phasic and late tonic visual responses often displayed different disparity sensitivity. These findings provide evidence of depth-related signals in FEF and suggest a role for FEF in the control of disconjugate as well as conjugate eye movements. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Ferraina, S (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,9000 Rockville Pike,Room 2A50, Bethesda, MD 20892 USA. NR 29 TC 53 Z9 53 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2000 VL 83 IS 1 BP 625 EP 629 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 274RA UT WOS:000084777800055 PM 10634901 ER PT J AU Mazzanti, B Hemmer, B Traggiai, E Ballerini, C McFarland, HF Massacesi, L Martin, R Vergelli, M AF Mazzanti, B Hemmer, B Traggiai, E Ballerini, C McFarland, HF Massacesi, L Martin, R Vergelli, M TI Decrypting the spectrum of antigen-specific T-cell responses: The avidity repertoire of MBP-specific T-cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE myelin basic protein; multiple sclerosis; T-cell response; antigen concentration ID MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS; FINE SPECIFICITY; PROTEOLIPID PROTEIN; CEREBROSPINAL-FLUID; HEALTHY-INDIVIDUALS; RECEPTOR USAGE; RECOGNITION; LINES; EPITOPES AB Myelin basic protein (MBP) is a well-characterized autoantigen potentially involved in the pathogenesis of the most common human demyelinating disease of the central nervous system (CNS), multiple sclerosis (MS). it is known that MBP-specific T-cell responses differ widely among different individuals and also within a single donor in terms of fine specificity and functional characteristics including the avidity in antigen recognition. In this report, we demonstrate that the in vitro selection of MBP-reactive T-cell repertoire is strictly dependent upon the antigen dose used in the primary cultures. MBP-specific T-cell lines (TCLs) were generated from MS patients and healthy donors using different antigen concentration in cultures (0.1 to 50 mu g/ml). In both MS patients and controls, the number of obtained T-cell lines was affected by the antigen concentration. In addition, low and high antigen concentrations selected in vitro different T-cell populations in terms of peptide specificity patterns and different functional avidities in antigen recognition. Low concentrations of MBP in the primary cultures yielded a small number of TCLs recognizing the specific antigen with higher avidity whereas high antigen concentrations allowed the in vitro expansion of a higher numbers of T-cells recognizing MBP with lower avidity. The use of different antigen concentrations in the primary cultures can be applied as a simple experimental system to investigate the overall avidity repertoire of antigen-specific T-cell response in humans. (C) 2000 Wiley-Liss, Inc. C1 Univ Florence, Dept Neurol & Psychiat Sci, I-50134 Florence, Italy. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD USA. Univ Marburg, Dept Neurol, Clin Neurimmunol Grp, Marburg, Germany. RP Vergelli, M (reprint author), Univ Florence, Dept Neurol & Psychiat Sci, Viale Morgagni 85, I-50134 Florence, Italy. RI traggiai, elisabetta/A-2316-2009; ballerini, clara/I-6460-2012; OI Massacesi, Luca/0000-0001-5083-372X; ballerini, clara/0000-0002-7812-9029 NR 34 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JAN 1 PY 2000 VL 59 IS 1 BP 86 EP 93 DI 10.1002/(SICI)1097-4547(20000101)59:1<86::AID-JNR10>3.0.CO;2-U PG 8 WC Neurosciences SC Neurosciences & Neurology GA 270ZY UT WOS:000084568000010 PM 10658188 ER PT J AU Levy, EI Heiss, JD Kent, MS Riedel, CJ Oldfield, EH AF Levy, EI Heiss, JD Kent, MS Riedel, CJ Oldfield, EH TI Spinal cord swelling preceding syrinx development - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE syringomyelia; Chiari malformation ID SYRINGOMYELIA; PATHOGENESIS AB The pathophysiology of syrinx development is controversial. The authors report on a patient with progressive cervical myelopathy and a Chiari I malformation in whom spinal cord swelling preceded, by a few months, the development of a syrinx in the same location. The patient underwent a craniocervical decompressive procedure and duraplasty, and complete resolution of cord swelling and syringomyelia was achieved. This report is consistent with the theory that patients with Chiari I malformation have increased transmural flow of cerebrospinal fluid, which causes spinal cord swelling that later coalesces into a syrinx. The pathophysiology of syrinx development from spinal cord edema and the success of surgical decompressive treatments that do not invade the central nervous system support the prompt treatment of patients with spinal cord edema who are at risk, for the development of a syrinx. C1 NIH, Surg Neurol Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Presbyterian Univ Hosp, Dept Neurol Surg, Pittsburgh, PA USA. Cornell Univ, Dept Neurol Surg, Ithaca, NY 14853 USA. Columbia Univ, New York, NY USA. Neurol Inst, Dept Neurol Surg, New York, NY USA. RP Heiss, JD (reprint author), NIH, Surg Neurol Branch, 10 Ctr Dr,10-5D37,MSC 1414, Bethesda, MD 20892 USA. NR 20 TC 38 Z9 40 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2000 VL 92 IS 1 SU S BP 93 EP 97 DI 10.3171/spi.2000.92.1.0093 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 271VU UT WOS:000084615400015 PM 10616064 ER PT J AU Pluta, RM Afshar, JKB Thompson, BG Boock, RJ Harvey-White, J Oldfield, EH AF Pluta, RM Afshar, JKB Thompson, BG Boock, RJ Harvey-White, J Oldfield, EH TI Increased cerebral blood flow but no reversal or prevention of vasospasm in response to L-arginine infusion after subarachnoid hemorrhage SO JOURNAL OF NEUROSURGERY LA English DT Article DE nitric oxide; subarachnoid hemorrhage; vasospasm; cerebral blood flow; L-arginine ID NITRIC-OXIDE SYNTHASE; GUANYLATE-CYCLASE; ENDOTHELIAL-CELLS; BASILAR ARTERY; MECHANISMS; ACTIVATION; PATHWAY; HYPERCAPNIA; ASTROCYTES; EXPRESSION AB Object. The reduction in the level of nitric oxide (NO) is a purported mechanism of delayed vasospasm after subarachnoid hemorrhage (SAH). Evidence in support of a causative role for NO includes the disappearance of nitric oxide synthase (NOS) from the adventitia of vessels in spasm, the destruction of NO by hemoglobin released from the clot into the subarachnoid space, and reversal of vasospasm by intracarotid NO. The authors sought to establish whether administration of L-arginine, the substrate of the NO-producing enzyme NOS, would reverse and/or prevent vasospasm in a primate model of SAH. Methods. The study was composed of two sets of experiments: one in which L-arginine was infused over a brief period into the carotid artery of monkeys with vasospasm, and the other in which L-arginine was intravenously infused into monkeys over a longer period of time starling at onset of SAH. In the short-term infusion experiment, the effect of a 3-minute intracarotid infusion of L-arginine (intracarotid concentration 10(-6)M) on the degree of vaso spasm of the right middle cerebral artery (MCA) and on regional cerebral blood flow (rCBF) was examined in five cynomolgus monkeys. In the long-term infusion experiment, the effect of a 14-day intravenous infusion of saline (control group, five animals) or L-arginine (10(-3) M; six animals) on the occurrence and degree of cerebral vasospasm was examined in monkeys. The degree of vasospasm in all experiments was assessed by cerebral arteriography, which was performed preoperatively and on postoperative Days 7 (short and long-term infusion experiments) and 14 (long-term infusion experiment). In the long-term infusion experiment, plasma revels of L-arginine were measured at these times in the monkeys to confirm L-arginine availability. Vasospasm was not affected by the intracarotid infusion of L-arginine (shown by the reduction in the right MCA area on an anteroposterior arteriogram compared with preoperative values). However, intracarotid L-arginine infusion in creased rCBF by 21% (p < 0.015; PCO2 38-42 mm Hg) in all vasospastic monkeys compared with rCBF measured during the saline infusions. In the long-term infusion experiment, vasospasm of the right MCA occurred with similar intensity with or without continuous intravenous administration of L-arginine on Day 7 and had resolved by Day 14. The mean plasma L-arginine level increased during infusion from 12.7 +/- 4 mu g/ml on Day 0 to 21.9 +/- 13.1 mu g/ml on Day 7 and was 18.5 +/- 3.1 mu g/ml on Day 14 (p < 0.05). Conclusions. Brief intracarotid and continuous intravenous infusion of L-arginine did not influence the incidence or degree of cerebral vasospasm. After SAH, intracarotid infusion of L-arginine markedly increased rCBF in a primate model of SAH. These findings discourage the use of L-arginine as a treatment for vasospasm after SAH. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D-37,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 63 TC 31 Z9 33 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2000 VL 92 IS 1 BP 121 EP 126 DI 10.3171/jns.2000.92.1.0121 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 268ZP UT WOS:000084451500016 PM 10616090 ER PT J AU Ashford, JW Shih, WJ Coupal, J Shetty, R Schneider, A Cool, C Aleem, A Kiefer, VH Mendiondo, MS Schmitt, FA AF Ashford, JW Shih, WJ Coupal, J Shetty, R Schneider, A Cool, C Aleem, A Kiefer, VH Mendiondo, MS Schmitt, FA TI Single SPECT measures of cerebral cortical perfusion reflect time-index estimation of dementia severity in Alzheimer's disease SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE Alzheimer's disease; SPECT; computer-assisted image processing; cognitive dysfunction; dementia severity ID STEREOTAXIC SURFACE PROJECTIONS; MINI-MENTAL-STATE; BLOOD-FLOW; BRAIN; DIAGNOSIS; PET; GLUCOSE; IMPAIRMENT; PARKINSONS; MODEL AB To determine the relationship between cerebral cortical blood flow loss and the temporal development of the dementia in Alzheimer's disease (AD), SPECT was studied in a cross section of AD patients with a broad range of impairment. Methods: Thirty patients with a diagnosis of probable AD had their mini-mental state examination scores transformed into time-index values to give an estimation of dementia severity relative to the developmental time course. SPECT images were obtained using Tc-99m-ethyl cysteinate dimer and a 3-head camera. Cortical surface perfusion was analyzed, including modified Talairach standardization, to obtain cortical elements from the convexity teach representing about 0.25 cm(2) at the surface, 6.6-mm cortical depth) referenced to the mean perfusion of the full greater cerebellar hemisphere. These element ratios were analyzed (individually and by averages of estimated Brodmann's areas and brain regions) using linear regression with the time-index value. Results: For individual posterotemporal and inferoparietal Brodmann's areas (21, 22 and 39, 40, respectively) the correlation coefficients between cortical perfusion ratios and dementia severity ranged between -0.67 and -0.78 (P < 0.001). Perfusion ratios from these regions declined 2.5%-4.2% for each estimated year of progression. Prefrontal area perfusion showed less association with severity. Perfusion in primary cortical regions had no significant association with dementia severity. Conclusion: Cerebral cortical perfusion loss is temporally related to development of dementia. The spatial pattern of high, significant correlations between cortical perfusion and dementia severity shows a regional distribution that corresponds closely to the distribution of AD pathology described in autopsy studies. C1 Univ Kentucky, Coll Med, Sanders Brown Ctr Aging, NIA,Dept Psychiat, Lexington, KY 40509 USA. Univ Kentucky, Coll Med, Sanders Brown Ctr Aging, NIA,Dept Neurol, Lexington, KY 40509 USA. Univ Kentucky, Coll Med, Sanders Brown Ctr Aging, NIA,Dept Diagnost Radiol, Lexington, KY 40509 USA. Univ Kentucky, Coll Med, Sanders Brown Ctr Aging, NIA,Dept Stat, Lexington, KY 40509 USA. Univ Kentucky, Coll Med, Sanders Brown Ctr Aging, NIA,Alzheimers Dis Res Ctr, Lexington, KY 40509 USA. Vet Affairs Med Ctr, Mental Hlth Serv, Lexington, KY USA. Vet Affairs Med Ctr, Nucl Med Serv, Lexington, KY USA. Vet Affairs Med Ctr, Med Serv, Lexington, KY USA. Vet Affairs Med Ctr, Nursing Serv, Lexington, KY USA. RP Ashford, JW (reprint author), Univ Kentucky, Coll Med, Sanders Brown Ctr Aging, NIA,Dept Psychiat, 3470 Blazer Pkwy, Lexington, KY 40509 USA. FU NIA NIH HHS [AG 10483, AG 05144] NR 41 TC 34 Z9 34 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2000 VL 41 IS 1 BP 57 EP 64 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 274JJ UT WOS:000084762500012 PM 10647605 ER PT J AU Harden, JT McFarland, G AF Harden, JT McFarland, G TI Avoiding gender and minority barriers to NIH funding SO JOURNAL OF NURSING SCHOLARSHIP LA English DT Article DE research subjects; clinical research; research administration; gender; minority ID CLINICAL RESEARCH AB Purpose: To inform investigators of the National Institutes of Health (NIH) guidelines for the inclusion of women and minorities as subjects in clinical research and provide tips on avoiding barriers to federal funding. Methods: Information about gender and minority barriers to funding was obtained by reviewing NIH policies, information submitted by applicants, and comments provided by NIH reviewers. Organizing Framework: A brief history of the goals of U.S. federal legislation to increase opportunities for obtaining information to help enhance health and disease treatment for all Americans and to detect and account for ethnic and gender differences is described. Examples were derived from NIH Summary Statement comments of initial review groups. Conclusions: Applications submitted to NIH are being barred from initial funding, even with excellent priority scores, if the plan for inclusion of women and minorities is judged to be scientifically unacceptable by the initial review group. This situation is correctable and avoidable. C1 NIA, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth, Ctr Sci Review, Bethesda, MD USA. RP Harden, JT (reprint author), NIA, NIH, Bldg 31,Room 5C35,31 Ctr Dr,MSC 2292, Bethesda, MD 20892 USA. NR 11 TC 12 Z9 12 U1 0 U2 0 PU SIGMA THETA TAU INT PI INDIANAPOLIS PA 550 W NORTH STREET, INDIANAPOLIS, IN 46202 USA SN 1527-6546 J9 J NURS SCHOLARSHIP JI J. Nurs. Scholarsh. PY 2000 VL 32 IS 1 BP 83 EP 86 DI 10.1111/j.1547-5069.2000.00083.x PG 4 WC Nursing SC Nursing GA 325YV UT WOS:000087705600019 PM 10819743 ER PT J AU Rouse, B Matalon, R Koch, R Azen, C Levy, H Hanley, W Trefz, F de la Cruz, F AF Rouse, B Matalon, R Koch, R Azen, C Levy, H Hanley, W Trefz, F de la Cruz, F TI Maternal phenylketonuria syndrome: Congenital heart defects, microcephaly, and developmental outcomes SO JOURNAL OF PEDIATRICS LA English DT Article ID MALFORMATIONS; POPULATION; PHENOTYPE; MUTATIONS; GENOTYPE AB Objective: A cohort of women with phenylketonuria (PKU) were selected to explore the impact of phenylalanine (Phe) levels and other factors on congenital heart defects (CHDs), microcephaly, and development of their offspring. Study design: Three hundred fifty-four women with PKU were followed up weekly with diet records, blood Phe levels, and sonograms obtained at 18 to 20 and 32 weeks' gestation. At birth, 413 offspring Lr ere examined and followed up at 6 months and annually by means of Bayley Mental Developmental Index and Psychomotor Developmental Index tests at 1 and 2 years. The women had Wechsler Adult Intelligence Scales and DNA testing. Results: Thirty-one offspring had CHDs; of these, 17 also had microcephaly Mean Phe levels at 4 to 8 weeks' gestation predicted CHDs (P < .0001), An infant with a CHD had a 3-fold risk of having microcephaly when the mother had higher Phe levels (P = .02). The Bayley Mental Developmental Index and Psychomotor Developmental Index scores correlated with both CHDs (P = .037 and .0015, respectively) and microcephaly (P = .0001 for both). No direct relationship to the PKU mutation was found. Conclusion: None of the women whose offspring had CHDs had blood Phe levels in control during the brat 8 weeks of gestation. Women with PKU need to be well controlled on a low-phenylalanine diet before conception and throughout pregnancy. (J Pediatr 2000;136:57-61). C1 Univ Texas, Med Branch, Childrens Hosp, Dept Pediat, Galveston, TX 77555 USA. Univ Illinois, Dept Human Nutr & Dietet, Chicago, IL USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Childrens Hosp, Boston, MA 02115 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Tuebingen, Kinderklin, Reutlingen, Germany. NICHHD, NIH, Bethesda, MD 20892 USA. RP Rouse, B (reprint author), Univ Texas, Med Branch, Childrens Hosp, Dept Pediat, 301 Univ Blvd, Galveston, TX 77555 USA. FU NICHD NIH HHS [N01-HD-2-3148, N01-HD-2-3149, N01-HD-2-3155] NR 18 TC 33 Z9 35 U1 1 U2 2 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 JAN PY 2000 VL 136 IS 1 BP 57 EP 61 DI 10.1016/S0022-3476(00)90050-7 PG 5 WC Pediatrics SC Pediatrics GA 277AF UT WOS:000084910000015 PM 10636975 ER PT J AU Grether, JK Nelson, KB AF Grether, JK Nelson, KB TI Possible decrease in prevalence of cerebral palsy in premature infants SO JOURNAL OF PEDIATRICS LA English DT Letter ID MORTALITY; TRENDS C1 Dept Hlth Serv, Calif Birth Defects Monitoring Program, Emeryville, CA 94608 USA. NINDS, Neuroepidemiol Branch, Bethesda, MD 20892 USA. RP Grether, JK (reprint author), Dept Hlth Serv, Calif Birth Defects Monitoring Program, Emeryville, CA 94608 USA. NR 4 TC 13 Z9 13 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 JAN PY 2000 VL 136 IS 1 BP 133 EP 133 DI 10.1016/S0022-3476(00)90071-4 PG 1 WC Pediatrics SC Pediatrics GA 277AF UT WOS:000084910000033 PM 10636990 ER PT J AU McCrae, RR Costa, PT Ostendorf, F Angleitner, A Hrebickova, M Avia, MD Sanz, J Sanchez-Bernardos, ML Kusdil, ME Woodfield, R Saunders, PR Smith, PB AF McCrae, RR Costa, PT Ostendorf, F Angleitner, A Hrebickova, M Avia, MD Sanz, J Sanchez-Bernardos, ML Kusdil, ME Woodfield, R Saunders, PR Smith, PB TI Nature over nurture: Temperament, personality, and life span development SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 106th Annual Convention of the American-Psychological-Association CY AUG 15-16, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Psychol Assoc ID INDIVIDUAL-DIFFERENCES; ADULT PERSONALITY; 5-FACTOR MODEL; TRAITS; SELF; DIMENSIONS; INVENTORY; STABILITY; CHILDREN; CULTURES AB Temperaments are often regarded as biologically based psychological tendencies with intrinsic paths of development. It is argued that this definition applies to the personality traits of the five-factor model. Evidence for the endogenous nature of traits is summarized from studies of behavior genetics, parent-child relations, personality structure, animal personality, and the longitudinal stability of individual differences. New evidence for intrinsic maturation is offered from analyses of NEO Five-Factor Inventory scores for men and women age 14 and over in German, British, Spanish, Czech, and Turkish samples (N = 5,085). These data support strong conceptual Links to child temperament despite modest empirical associations. The intrinsic maturation of personality is complemented by the culturally conditioned development of characteristic adaptations that express personality; interventions in human development are best addressed to these. C1 NIA, Personal Stress & Coping Sect, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Bielefeld, Dept Psychol, D-4800 Bielefeld, Germany. Acad Sci Czech Republ, Inst Psychol, Brno, Czech Republic. Univ Complutense Madrid, Dept Psychol, Madrid, Spain. Univ Sussex, Sch Social Sci, Brighton BN1 9RH, E Sussex, England. RP McCrae, RR (reprint author), NIA, Personal Stress & Coping Sect, Gerontol Res Ctr, NIH, Box 3,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Sanchez-Bernardos, Maria Luisa/C-6038-2011; Avia, Maria Dolores/C-7061-2011; Sanz, Jesus/B-9175-2008; Woodfield, Ruth/A-3797-2013; Hrebickova, Martina/H-4410-2014; Kusdil, Muharrem/D-2834-2016; OI Sanchez-Bernardos, Maria Luisa/0000-0003-4931-867X; Sanz, Jesus/0000-0003-2229-1665; Hrebickova, Martina/0000-0003-4356-567X; Costa, Paul/0000-0003-4375-1712 NR 94 TC 503 Z9 512 U1 20 U2 160 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD JAN PY 2000 VL 78 IS 1 BP 173 EP 186 DI 10.1037/0022-3514.78.1.173 PG 14 WC Psychology, Social SC Psychology GA 274HT UT WOS:000084760900013 PM 10653513 ER PT J AU Bauer, KS Cude, KJ Dixon, SC Kruger, EA Figg, WD AF Bauer, KS Cude, KJ Dixon, SC Kruger, EA Figg, WD TI Carboxyamido-triazole inhibits angiogenesis by blocking the calcium-mediated nitric-oxide synthase-vascular endothelial growth factor pathway SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SIGNAL-TRANSDUCTION; TUMOR ANGIOGENESIS; CELL-LINES; RELEASE; PHARMACOKINETICS; METASTASIS; INDUCTION; L-651,582; CARCINOMA; GAMMA AB The induction of angiogenesis is known to play a critical role in the successful growth, invasion, and metastasis of a tumor. A tumor will not grow beyond a few cubic millimeters without the formation of its own capillary network. Several antiangiogenic agents are under investigation in the clinic setting for the treatment of cancer. Carboxyamido-triazole (CAI), an inhibitor of Ca2+-mediated signal transduction, has been previously shown to inhibit angiogenesis in vitro and in vivo and to downregulate matrix metalloproteinase-2 in vitro. Diminished levels of intracellular Ca2+ result in decreased nitric-oxide synthase (NOS) activity and thereby inhibit the production and release of NO. The antiangiogenic activity of CAI was investigated by assessing microvessel growth from rat aortic segments and in cell culture using human aortic endothelial cells (HAECs). With these models, vascular endothelial growth factor (VEGF) and NOS production and secretion were evaluated. CAI concentrations ranging from 0.25 to 12.0 mu g/ml inhibited new microvessel formation in rat aortic cultures and HAEC proliferation in a dose-dependent manner. Additionally, HAECs treated with CAI showed a dose-dependent decrease of NOS expression and a decrease in both VEGF expression and secretion. Rat aortic segments demonstrated decreased VEGF expression in situ on immunostaining. These data suggest that modulation of the NOS-NO-VEGF pathway through Ca2+-mediated signaling by CAI inhibits angiogenesis in vitro. C1 NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Div Clin Sci, Med Branch, NIH, Bldg 10,Room 5A01,10 Ctr Dr, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 28 TC 42 Z9 44 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2000 VL 292 IS 1 BP 31 EP 37 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 267AD UT WOS:000084331700006 PM 10604929 ER PT J AU Chahdi, A Fraundorfer, PF Beaven, MA AF Chahdi, A Fraundorfer, PF Beaven, MA TI Compound 48/80 activates mast cell phospholipase D via heterotrimeric GTP-binding proteins SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ARACHIDONIC-ACID RELEASE; RBL-2H3 CELLS; SUBSTANCE-P; KINASE-C; HISTAMINE-SECRETION; EXOCYTOSIS; RECEPTORS; LINE; MASTOPARAN; ALPHA AB Previous studies have indicated the presence of a cholera toxin-sensitive phospholipase D (PLD) in cultured RBL-2H3 mast cells that is synergistically activated via calcium, protein kinase C, and another unidentified signal. Here we identify a third potential signal for activation transduced by a pertussis toxin-sensitive trimeric GTP-binding protein, most likely via G(i2) or G(i3). Quercetin-treated RBL-2H3 cells in which expression of G(alpha i2) and G(alpha i3) is enhanced more than 7-fold respond to the G(i) stimulant compound 48/80 with the activation of PLD, a transient activation of phospholipase C, and enhanced membrane GTPase activity. The activation of PLD was blocked in pertussis toxin-treated cells and, as with other stimulants of PLD, was enhanced in cholera toxin-treated cells. The PLD response to compound 48/80 was only partially inhibited by calcium deprivation and inhibition of protein kinase C to indicate a component of the response that was independent of calcium, protein kinase C, and, presumably, phospholipase C. Based on these and other data, we hypothesized that beta gamma-subunits, released from G(i2) or G(i3) by compound 48/80 or from G(s) by cholera toxin, provide an additional signal for the activation of PLD. Consistent with this hypothesis, recombinant G(beta 2 gamma 2) subunits, but not G(alpha i-3) subunits, at concentrations of 50 to 300 nM markedly synergized PLD activation by compound 48/80 in permeabilized RBL-2H3 cells. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, NIH, Room 8N109 Bldg 10, Bethesda, MD 20892 USA. NR 40 TC 52 Z9 54 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2000 VL 292 IS 1 BP 122 EP 130 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 267AD UT WOS:000084331700015 PM 10604938 ER PT J AU Du, J Haak, LL Phillips-Tansey, E Russell, JT McBain, CJ AF Du, J Haak, LL Phillips-Tansey, E Russell, JT McBain, CJ TI Frequency-dependent regulation of rat hippocampal somato-dendritic excitability by the K+ channel subunit Kv2.1 SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID POTASSIUM-CHANNEL; FUNCTIONAL-CHARACTERIZATION; PYRAMIDAL NEURONS; EXPRESSION; INTERNEURONS; BRAIN; IDENTIFICATION; ANTISENSE; CELLS; CULTURES AB 1. The voltage-dependent potassium channel subunit Kv2.1 is widely expressed throughout the mammalian CNS and is clustered primarily on the somata and proximal dendrites, but not axons, of both principal neurones and inhibitory interneurones of the cortex and hippocampus. This expression pattern suggests that Kv2.1-containing channels may play a role in the regulation of pyramidal neurone excitability. To test this hypothesis and to determine the functional role of Kv2.1-containing channels, cultured hippocampal slices were incubated with antisense oligonucleotides directed against Kv2.1 mRNA. 2. Western blot analysis demonstrated that Kv2.1 protein content of cultured slices decreased > 90 % following 2 weeks of treatment with antisense oligonucleotides, when compared with either control missense-treated or untreated cultures. Similarly, Kv2.1 immunostaining was selectively decreased in antisense-treated cultures. 3. Sustained outward potassium currents, recorded in both whole-cell and outside-out patch configurations, demonstrated a selective reduction of amplitude only in antisense-treated CA1 pyramidal neurones. 4. Under current-clamp conditions, action potential durations were identical in antisense-treated, control missense-treated and untreated slices when initiated by low frequency stimulation (0.2 Hz). In contrast, spike repolarization was progressively prolonged during higher frequencies of stimulation (1 Hz) only in cells from antisense-treated slices. Similarly action potentials recorded during electrographic interictal activity in the 'high [K+](o)' model of epilepsy demonstrated pronounced broadening of their late phase only in cells fi om antisense-treated slices. 5. Consistent with the frequency-dependent spike broadening, calcium imaging experiments from single CA1 pyramidal neurones revealed that high frequency Schaffer collateral stimulation resulted in a prolonged elevation of dendritic [Ca2+](i) transients only in antisense-treated neurones. 6. These studies demonstrate that channels containing Kv2.1 play a role in regulating pyramidal neurone somato-dendritic excitability primarily during episodes of high frequency synaptic transmission. C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP McBain, CJ (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, Room 5A72,49 Convent Dr, Bethesda, MD 20892 USA. RI Haak, Laurel/C-4986-2008; Du, Jing/A-9023-2012 OI Haak, Laurel/0000-0001-5109-3700; NR 32 TC 128 Z9 131 U1 1 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN 1 PY 2000 VL 522 IS 1 BP 19 EP 31 DI 10.1111/j.1469-7793.2000.t01-2-00019.xm PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 279GT UT WOS:000085036600003 PM 10618149 ER PT J AU Omata, Y Dai, RK Smith, SV Robinson, RC Friedman, FK AF Omata, Y Dai, RK Smith, SV Robinson, RC Friedman, FK TI Synthetic peptide mimics of a predicted topographical interaction surface: The cytochrome P4502B1 recognition domain for NADPH-cytochrome P450 reductase SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE protein structure; protein-protein interactions; peptide mimics; cytochrome P450; drug metabolism ID SITE-DIRECTED MUTAGENESIS; ELECTRON-TRANSFER COMPLEX; NADPH-CYTOCHROME-P-450 REDUCTASE; MONOCLONAL-ANTIBODY; RESIDUES; PURIFICATION; INHIBITION; MECHANISM; LYSINE; MODEL AB In order to identify the cytochrome P450-binding domain for NADPH-cytochrome P450 reductase, synthetic peptide mimics of predicted surface regions of rat cytochrome P450 2B1 were constructed and evaluated for inhibition of the P450-reductase interaction. A peptide corresponding to residues 116-134, which includes the C helix, completely inhibited reductase-mediated benzphetamine demethylation by purified P450 2B1. Replacement of Arg-125 by Glu yielded a noninhibitory peptide, suggesting that this residue significantly contributes to the reductase-P450 interaction. Additional P450 peptides were prepared which correspond to combinations of regions distant in primary sequence, but predicted to-he spatially proximate. A peptide derived from segments of the C and L helices was a more potent inhibitor than peptides derived from either segment alone. This topographically designed peptide not only inhibited P450 2B1 in its purified form, but also when membrane-bound in rat liver microsomes. The peptide also inhibited microsomal aryl hydrocarbon hydroxylase, aniline hydroxylase, and erythromycin demethylase activities derived from other P450s. These results indicate that the C and L helices contribute to a reductase-binding site common to multiple P450s, and present a peptide mimic for this region that is useful for inhibition of P450-mediated microsomal activities. C1 NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Friedman, FK (reprint author), NCI, Mol Carcinogenesis Lab, Bldg 37,Room 3E-24, Bethesda, MD 20892 USA. RI Friedman, Fred/D-4208-2016 NR 36 TC 7 Z9 7 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JAN PY 2000 VL 19 IS 1 BP 23 EP 32 DI 10.1023/A:1007038724874 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 327DJ UT WOS:000087777700003 PM 10882169 ER PT J AU Vawter, MP Frye, MA Hemperly, JJ VanderPutten, DM Usen, N Doherty, P Saffell, JL Issa, F Post, RM Wyatt, RJ Freed, WJ AF Vawter, MP Frye, MA Hemperly, JJ VanderPutten, DM Usen, N Doherty, P Saffell, JL Issa, F Post, RM Wyatt, RJ Freed, WJ TI Elevated concentration of N-CAM VASE isoforms in schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE schizophrenia; bipolar disorder; cerebrospinal fluid; electrophoresis; neural cell adhesion molecule; variable alternative spliced exon; Western immunoblot; psychiatric symptom assessment scale; Hamilton depression rating scale ID CELL-ADHESION MOLECULE; LONG-TERM POTENTIATION; NEURITE OUTGROWTH; CEREBROSPINAL-FLUID; RECOGNITION MOLECULES; CYTOPLASMIC DOMAIN; CDNA CLONES; RAT-BRAIN; NCAM; L1 AB Neural cell adhesion molecule (N-CAM) is a cell recognition molecule, four major isoforms (180: 140, 120, and 105-115 kDa) of which are present in brain. N-CAM has several roles in cellular organization and CNS development. Previously we have found an elevation in CSF N-CAM 120 kDa in the CSF of patients with schizophrenia, bipolar disorder, and depression. We now report an increase in the variable alternative spliced exon (VASE), a 10 amino acid sequence inserted into the fourth N-CAM domain, in the CSF of patients with schizophrenia, but not in bipolar disorder or depression. VASE-immunoreactive (VASE-ir) bands were measured in CSF from patients with schizophrenia (n = 14), bipolar disorder I (n = 7), bipolar disorder II (n = 9), unipolar depression (n = 17) and matched controls (n = 37) by Western immunoblotting. Three VASE-ir bands were distinguished in lumbar CSF corresponding to heavy (165 kDa), medium (155 kDa) and low (140 kDa) MW. A logarithmic transformation was applied to the VASE protein units and analyzed with a MANOVA. There was a 51% and 45% increase in VASE heavy (p = 0.0008) and medium (p = 0.04) MW protein, respectively, in patients with schizophrenia as compared with normal controls. Current neuroleptic treatment in patients with schizophrenia had no effect on CSF VASE concentrations. VASE concentration correlated significantly with behavioral ratings in patients with schizophrenia but not affective disorders. Thus, VASE immunoreactivity is increased in schizophrenia but not in affective disorders. These results provide further evidence of an abnormality of N-CAM protein in chronic schizophrenia and suggest differences between schizophrenia and affective disorders in regulation of N-CAM. Published by Elsevier Science Ltd. C1 NIDA, Cellular Neurobiol Branch, IRP, Baltimore, MD 21224 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Lab Biochem Genet, Bethesda, MD 20892 USA. NIMH, Neuropsychiat Branch, Bethesda, MD 20892 USA. Becton Dickinson & Co, Res Ctr, Neurobiol Sect, Res Triangle Pk, NC 27709 USA. Guys Hosp, Dept Expt Pathol, London SE1 9RT, England. RP Vawter, MP (reprint author), NIDA, Cellular Neurobiol Branch, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Doherty, Patrick/A-8752-2008 NR 56 TC 30 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD JAN-FEB PY 2000 VL 34 IS 1 BP 25 EP 34 DI 10.1016/S0022-3956(99)00026-6 PG 10 WC Psychiatry SC Psychiatry GA 281FG UT WOS:000085146800005 PM 10696830 ER PT J AU Aitchison, KJ Jann, MW Zhao, JH Sakai, T Zaher, H Wolff, K Collier, DA Kerwin, RW Gonzalez, FJ AF Aitchison, KJ Jann, MW Zhao, JH Sakai, T Zaher, H Wolff, K Collier, DA Kerwin, RW Gonzalez, FJ TI Clozapine pharmacokinetics and pharmacodynamics studied with CYP1A2-null mice SO JOURNAL OF PSYCHOPHARMACOLOGY LA English DT Article DE clozapine; CYP1A2; cytochrome P450; knockout; metabolism; pharmacodynamics; pharmacokinetics ID REFRACTORY SCHIZOPHRENIC-PATIENTS; INDUCED AGRANULOCYTOSIS; CLINICAL-RESPONSE; PLASMA CLOZAPINE; IN-VITRO; N-DESMETHYLCLOZAPINE; 5'-FLANKING REGION; HUMAN NEUTROPHILS; METABOLISM; PHENOTYPES AB The aim of this study was to use the CYP1A2-null mouse to investigate the in-vivo contribution of CYP1A2 to clozapine pharmacokinetics and pharmacodynamics. An intraperitoneal injection of 10 mg/kg clozapine was administered to four male CYP1A2 -/- mice and four male wild-type mice. Clozapine, desmethylclozapine, and clozapine N-oxide concentrations in sequential tail blood samples were measured by HPLC with UV detection. Behavioural parameters were recorded at each time point. The area under the curve (AUC) of clozapine was 2.6 times greater, the clearance of clozapine was 2.6 times slower, and the half-life was 1.2 times longer in the CYP1A2 -/- mice (p = 0.0143) as compared to the wild-type mice. Sixty-one percent of the clozapine clearance in wild-type mice was calculated to be mediated by CYP1A2, The AUC of desmethylclozapine was 1.6 times lower in the CYP1A2 -/- mice compared to the wild-type mice (p = 0.0286), while there was a trend for the AUC of clozapine N-oxide to be greater in the CYP1A2 -/- mice (p = 0.0571). The CYP1A2 -/- mice were significantly more drowsy and showed more motor impairment (p = 0.0145) and myoclonus than the wild-type mice. Our results indicate that, in vivo, CYP1A2 is the major determinant of clozapine clearance, contributes significantly to the demethylation of clozapine, and has a negligible contribution to the N-oxidation, Our data also indicate that CYP1A2 poor metabolizers might be more susceptible than extensive metabolizers to dose-related adverse effects of clozapine, such as sedation, myoclonus and seizures. C1 Inst Psychiat, Clin Pharmacol Sect, London SE5 8AF, England. Inst Psychiat, Sect Genet Epidemiol & Biostat, London SE5 8AF, England. Mercer Univ Pharm Practice, Atlanta, GA USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Natl Addict Ctr, London, England. RP Aitchison, KJ (reprint author), Inst Psychiat, Clin Pharmacol Sect, 1 Windsor Walk,Denmark Hill, London SE5 8AF, England. RI Aitchison, Katherine/G-4476-2013 OI Aitchison, Katherine/0000-0002-1107-3024 NR 61 TC 24 Z9 24 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 0269-8811 J9 J PSYCHOPHARMACOL JI J. Psychopharmacol. PY 2000 VL 14 IS 4 BP 353 EP 359 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 389UZ UT WOS:000166258200005 PM 11198052 ER PT J AU Hamann, HA Croyle, RT Smith, KR Quan, BNM McCance, KL Botkin, JR AF Hamann, HA Croyle, RT Smith, KR Quan, BNM McCance, KL Botkin, JR TI Interest in a support group among individuals tested for a BRCA1 gene mutation SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-for-Behavioral-Medicine CY MAR, 1998 CL NEW ORLEANS, LOUISIANA SP Soc Behav Med, MacArthur Fdn Res Network Successful Aging DE support group; cancer; genetic testing ID STRUCTURED PSYCHIATRIC INTERVENTION; BREAST-OVARIAN CANCER; SELF-HELP GROUPS; DECISION-MAKING; FAMILY HISTORY; ASHKENAZI JEWS; GROUP-THERAPY; MENTALLY-ILL; EVENT SCALE; NON-MEMBERS AB This article explores interest in a support group among 218 individuals tested for a mutation in BRCA1, a breast and ovarian cancer susceptibility gene. When queried 4 to 7 months after receiving the BRCA1 test results, approximately one-fourth of the participants expressed interest in a hypothetical support group. A mixed-carrier status and multiple family group was preferred over a carrier-only and single-family group. The information about interest in a support group among individuals tested for a BRCA1 mutation represents an important step in identifying those who are most receptive to psychosocial interventions. C1 Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA. NCI, Bethesda, MD 20892 USA. Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. Univ Utah, Dept Family & Consumer Studies, Salt Lake City, UT 84112 USA. RP Hamann, HA (reprint author), Univ Utah, Dept Psychol, 390 South 1530 East,Room 502, Salt Lake City, UT 84112 USA. NR 62 TC 6 Z9 6 U1 1 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2000 VL 18 IS 4 BP 15 EP 37 DI 10.1300/J077v18n04_02 PG 23 WC Psychology, Social SC Psychology GA 388BL UT WOS:000166157500002 ER PT J AU Boyer, GS Templin, DW Bowler, A Lawrence, RC Heyse, SP Everett, DF Cornoni-Huntley, JC Goring, WP AF Boyer, GS Templin, DW Bowler, A Lawrence, RC Heyse, SP Everett, DF Cornoni-Huntley, JC Goring, WP TI Spondyloarthropathy in the community: Differences in severity and disease expression in Alaskan Eskimo men and women SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE spondyloarthropathy; men; women; clinical comparison; severity ID ANKYLOSING-SPONDYLITIS; REACTIVE ARTHRITIS; CRITERIA AB Objectives. To determine the relative severity and compare the clinical expression of spondyloarthropathy (SpA) in men and women. Methods, A clinical study was conducted in 43 women and 40 men who made up 80% of all individuals identified as having SpA in a community-wide epidemiologic study of Alaskan Eskimos. The study included interviews, physical, laboratory, radiographic and electrocardiographic examinations, record reviews, and functional assessments. A measure of relative severity was developed to evaluate disease impact in individual patients. The results in men and women were compared. Results. No significant differences between men and women were found in many features, including the age of onset, frequency of inflammatory joint swelling or inflammatory back pain, physical signs of sacroiliitis, presence of skin changes, or positive family history of SpA. Women were less likely to have sacroiliac joint fusion, advanced spinal changes, uveitis, severe cardiac conduction and valvular abnormalities, and elevated erythrocyte sedimentation rates. According to our relative severity measure, a smaller proportion of women had severe disease than men. Conclusion. Although as many women as men were affected by SpA in the communities studied, severe disease was seen more often in men and a number of disease manifestations were more frequent or mon marked in men. These discrepancies in disease severity and expression may contribute to the underdiagnosis of SpA in women and the long standing impression that SpA is a disease predominantly of men. C1 Alaska Area Nat Hlth Serv, Anchorage, AK USA. NIAMSD, Bethesda, MD 20892 USA. NEI, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. Duke Univ, Sch Publ Hlth, Durham, NC USA. Univ Arizona, Off Vice President Res, Tucson, AZ USA. RP Boyer, GS (reprint author), 500 E Rudasill Rd, Tucson, AZ 85704 USA. FU NIAMS NIH HHS [YO2-AR-00005-02] NR 28 TC 10 Z9 11 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2000 VL 27 IS 1 BP 170 EP 176 PG 7 WC Rheumatology SC Rheumatology GA 274RC UT WOS:000084778000029 PM 10648035 ER PT J AU Edmond, SL Felson, DT AF Edmond, SL Felson, DT TI Prevalence of back symptoms in elders SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE back pain; prevalence; elderly; sex; age ID DESCRIPTIVE EPIDEMIOLOGY; SECULAR TRENDS; UNITED-STATES; PAIN; POPULATION; DISABILITY; COMMUNITY; MORTALITY; BRITAIN; HEALTH AB Objective, The prevalence of back pain has not been well studied in elders in the US. We describe the prevalence of back symptoms in a cohort of elderly subjects residing in the US by age, sex, examination site, and location of pain. Methods. Data from this study are based on 1037 surviving members of the original Framingham Heart Study cohort aged 68-100 years who participated in the 22nd biennial examination in 1992-93, Subjects were questioned about back pain and timing and location of pain. Results. Prevalence estimates varied, depending on the question used to assess back symptoms and the manner in which the question was asked. For example, back symptoms on most days occurred in 22.3 of 100 elders. Low back symptoms were more prevalent than those in the mid or upper back. Prevalence was higher among women than men, especially for symptoms in the mid or upper back area. Age did not affect the prevalence of back symptoms in this elderly cohort. Back symptoms were also more prevalent among subjects who were examined in their residence than among those who were examined at the examination site. Most subjects who were examined at their residence chose this location for health reasons. Conclusion. Back symptoms are highly prevalent in the elderly, although, among elders, they do not increase in prevalence with age. They are more common in women than men. Elders confined mostly to their homes have an especially high prevalence of back symptoms. C1 Boston Univ, Arthrit Ctr, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Edmond, SL (reprint author), Calif State Univ Sacramento, Phys Therapy Degree Program, 6000 J St, Sacramento, CA 95819 USA. FU NHLBI NIH HHS [N01-HC-38038]; NIA NIH HHS [AG09300]; NIAMS NIH HHS [AR20613] NR 25 TC 31 Z9 33 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JAN PY 2000 VL 27 IS 1 BP 220 EP 225 PG 6 WC Rheumatology SC Rheumatology GA 274RC UT WOS:000084778000036 PM 10648042 ER PT J AU Dawson, DA AF Dawson, DA TI Drinking patterns among individuals with and without DSM-IV alcohol use disorders SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID HEALTH INTERVIEW SURVEY; UNITED-STATES; III-R; DIAGNOSTIC-CRITERIA; GENERAL-POPULATION; DEPENDENCE; ABUSE; CONSUMPTION; DRINKERS; SAMPLE AB Objective: The purpose of this study was to compare alcohol consumption patterns among individuals with and without alcohol use disorders, using a representative sample of the general population that would not exaggerate differences as a result of selection biases associated with treatment for alcohol problems. Method: Based on data from 18,352 past-year drinkers selected from a nationally representative sample of U.S. households, 11 measures of past-year alcohol consumption were compared for three diagnostic groups: (1) individuals who did not meet the criteria for either alcohol abuse or dependence, i.e., those without a DSM-TV alcohol use disorder (AUD); (2) those classified with abuse only; and (3) those classified with alcohol dependence, with or without abuse. Results: For all measures reflecting frequency and quantity of drinking, frequency of heavy drinking and intoxication, and frequency of atypical temporal drinking patterns, the values for abusers lay midway between those for individuals without an AUD and those with dependence. Individuals with alcohol use disorders drank a greater proportion of their ethanol intake in the form of beer and a lower proportion in the form of wine than did those without an AUD. Of all the consumption measures considered, frequency of intoxication showed the strongest association with the probability of having an AUD, followed by frequency of drinking 5 + drinks, prevalence of morning drinking and total volume of intake. The ratios of consumption measures for individuals with disorders relative to those without an AUD showed relatively little significant variation across demographic subgroups of the population. Conclusions: The findings supported the distinction between the disorders of alcohol abuse and dependence, and implicated loss of control as an important element of this distinction. They also indicated that even among individuals with alcohol use disorders, demographic differentials reflecting cultural, physiological and normative forces were maintained and should be considered in approaches to treatment. C1 NIAAA, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Div Biometry & Epidemiol, NIH, Willco Bldg,Suite 514,6000 Execut Blvd MSC 7003, Bethesda, MD 20892 USA. NR 46 TC 40 Z9 41 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JAN PY 2000 VL 61 IS 1 BP 111 EP 120 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 266VQ UT WOS:000084321300015 PM 10627104 ER PT J AU Dawson, DA Room, R AF Dawson, DA Room, R TI Towards agreement on ways to measure and report drinking patterns and alcohol-related problems in adult general population surveys: the Skarpo Conference overview SO JOURNAL OF SUBSTANCE ABUSE LA English DT Article; Proceedings Paper CT Conference of the Kettil-Bruun-Society for Social and Epidemiological Research on Alcohol CY APR 02-07, 2000 CL SKARPO, SWEDEN SP Kettil Bruun Soc DE consumption; social harm; measurement ID CONSUMPTION MEASURES; GENDER DIFFERENCES; WORKSHOP; HARM AB A thematic conference of the Kettil Bruun Society (KBS) for Social and Epidemiological Research on Alcohol was held in Skarpo, near Stockholm, on April 3-7, 2000. The goals of the meeting were to develop consensus sets of questionnaire items for measuring alcohol consumption and social harm, to delineate statistical and practical concerns related to the aggregation of consumption and harm data and to identify summary measures to be used for descriptive purposes and in analyses of the association between alcohol intake and alcohol-related outcomes. The results of the conference discussions are summarized below, with emphasis on both areas where the conference yielded recommendations for measures and methods of aggregation for analysis, and on areas where consensus could not be obtained and/or where additional research is needed. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIAAA, DBE, NIH, Bethesda, MD 20892 USA. Stockholm Univ, Ctr Social Res Alcohol & Drugs, S-10691 Stockholm, Sweden. RP Dawson, DA (reprint author), NIAAA, DBE, NIH, Suite 514,Willco Bldg,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 30 TC 109 Z9 110 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-3289 J9 J SUBST ABUSE JI J. SUBST. ABUSE PY 2000 VL 12 IS 1-2 BP 1 EP 21 DI 10.1016/S0899-3289(00)00037-7 PG 21 WC Substance Abuse SC Substance Abuse GA 414CP UT WOS:000167648600001 PM 11288465 ER PT J AU Dawson, DA AF Dawson, DA TI Alternative measures and models of hazardous consumption SO JOURNAL OF SUBSTANCE ABUSE LA English DT Article; Proceedings Paper CT Conference of the Kettil-Bruun-Society for Social and Epidemiological Research on Alcohol CY APR 02-07, 2000 CL SKARPO, SWEDEN SP Kettil Bruun Soc DE hazardous consumption; social problems; acute outcomes ID ALCOHOL; RISK; DRINKING; HARM AB Hazardous alcohol consumption has been conceptualized (1) as all alcohol consumed on days when some threshold, usually approximate to 60 g, is exceeded, and (2) as only that portion of intake that exceeds this threshold. The first measure is hypothesized to be a better predictor of acute alcohol-related outcomes, because of its greater capacity to discriminate between individuals who frequently exceed the hazardous threshold by a small amount and those who infrequently exceed the threshold by a large amount. To test this hypothesis, the two approaches were used to construct alternative estimates of a number of measures of hazardous consumption. Individually and in combination, these measures were compared in a series of multiplicative models predicting four alcohol-related outcomes: impaired driving, fighting, interpersonal problems and injuries. There was no consistent evidence for one approach being superior to the other as a predictor of these outcomes. In fact, the use of appropriate linear transformations of the consumption variables had a far greater effect on improving the proportion of variance explained. The most highly predictive models were those based on frequency of hazardous consumption, mean volume of hazardous intake consumed per hazardous drinking day, volume of nonhazardous intake and their interactions. Differences among models were small, and models using combinations of simple, easy-to-obtain measures performed nearly on a par with those utilizing far more complex measures. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIAAA, DBE, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, DBE, NIH, Willco Bldg,Suite 514,6000 Execut Blvd,MSC 7003, Bethesda, MD 20892 USA. NR 17 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-3289 J9 J SUBST ABUSE JI J. SUBST. ABUSE PY 2000 VL 12 IS 1-2 BP 79 EP 91 DI 10.1016/S0899-3289(00)00041-9 PG 13 WC Substance Abuse SC Substance Abuse GA 414CP UT WOS:000167648600006 PM 11288476 ER PT J AU Faden, VB Graubard, BI AF Faden, VB Graubard, BI TI Maternal substance use during pregnancy and developmental outcome at age three SO JOURNAL OF SUBSTANCE ABUSE LA English DT Article DE substance use; pregnancy; development; behavior ID PRENATAL ALCOHOL EXPOSURE; FOLLOW-UP; MOTOR DEVELOPMENT; MARIJUANA USE; CHILDREN; CIGARETTES; GROWTH; BIRTH; DRINKING; DEFICITS AB Purpose: The data from the National Maternal and Infant Health Survey (NMIHS) and its 3-year follow-up offer a unique opportunity to study the effects of substance (alcohol, marijuana, and tobacco) use during gestation on development at age three in a nationally representative sample. Using this data, the relationship of development (language, gross motor, fine motor, and adaptive behavior) and specific behaviors (eating problems, length of play, activity level, difficulty of management, level of happiness, fearfulness, ability to get along with peers, tantrums, eating nonfood) and maternal drinking, marijuana use, and cigarette smoking was studied in a sample of live births who had been followed up at age three. Methods: The data were analyzed using a cumulative legit model of ordinal responses. Results: Higher activity level, greater difficulty of management, tantrums, eating problems, and eating nonfood were related to maternal drinking during pregnancy. Increased fearfulness, poorer motor skills, and shorter length of play were associated with maternal marijuana use during pregnancy. Less well developed language, higher activity level, greater difficulty of management, fearfulness, decreased ability to get along with peers, and increased tantrums were associated with maternal cigarette smoking during pregnancy. The preponderance of significant effects involved the behaviors studied rather than the developmental indices. Implications: It may be that the effects of substance use during pregnancy, especially more subtle ones, show up in behavior before they can be measured by developmental scales. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIAAA, Div Biometry & Epidemiol, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RP Faden, VB (reprint author), NIAAA, Div Biometry & Epidemiol, 6000 Execut Blvd, Bethesda, MD 20892 USA. NR 31 TC 48 Z9 48 U1 10 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-3289 J9 J SUBST ABUSE JI J. SUBST. ABUSE PY 2000 VL 12 IS 4 BP 329 EP 340 DI 10.1016/S0899-3289(01)00052-9 PG 12 WC Substance Abuse SC Substance Abuse GA 447EY UT WOS:000169559400002 PM 11452837 ER PT J AU Ernst, M Cookus, BA Moravec, BC AF Ernst, M Cookus, BA Moravec, BC TI Pictorial Instrument for Children and Adolescents (PICA-III-R) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE diagnosis; conduct disorder; childhood psychosis; depression; visual analog scale ID DIAGNOSTIC INTERVIEW SCHEDULE; STRUCTURED PSYCHIATRIC INTERVIEW; RELIABILITY; SYMPTOMS; AGREEMENT; VALIDITY; PARENT; SCALE; DISK AB Objective: The Pictorial Instrument for Children and adolescents (PICA-III-R) is presented as part of a comprehensive review of the tools used to diagnose psychiatric disorders in children and adolescents. Method: The PICA-III-R's development, content, initial psychometric properties, and directions for use are described. Results: The PICA-III-R assesses all DSM-III-R Axis I psychiatric disorders in children aged 6 to 16 years, categorically (diagnosis present or absent) and dimensionally (range of severity). It comprises 137 pictures organized in modules that cover 5 diagnostic categories, including disorders of anxiety, mood, psychosis, disruptive behavior, and substance abuse. Its initial psychometric properties are promising, with good internal consistency, significant discriminative power for diagnoses, and sensitivity to changes. Conclusions: Despite great interest expressed by child and adolescent psychiatrists, further testing has not been possible for practical reasons unrelated to the scientific Importance of such work. Although it needs to be modified to follow DSM-IV criteria, the PICA-III-R can be of significant help to child and adolescent psychiatrists, far clinical as well as research diagnostic purposes. In addition, it can be used for the assessment of non-English-speaking or hearing/speech-impaired children. C1 NIDA, Brain Imaging Ctr, NIH, Baltimore, MD 21224 USA. RP Ernst, M (reprint author), NIDA, Brain Imaging Ctr, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 23 TC 16 Z9 16 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2000 VL 39 IS 1 BP 94 EP 99 DI 10.1097/00004583-200001000-00021 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 270CT UT WOS:000084518400021 PM 10638072 ER PT J AU Albert, MR Mackool, BT AF Albert, MR Mackool, BT TI A dermatology ward at the beginning of the 20th century SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article C1 Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Consultat & Inpatient Serv, Boston, MA USA. RP Albert, MR (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,12N262,10 Ctr Dr, Bethesda, MD 20892 USA. NR 47 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2000 VL 42 IS 1 BP 113 EP 123 DI 10.1016/S0190-9622(00)90018-5 PN 1 PG 11 WC Dermatology SC Dermatology GA 272VQ UT WOS:000084672000015 PM 10607329 ER PT J AU Cohen, C Turner, ML Stratakis, CA AF Cohen, C Turner, ML Stratakis, CA TI Pigmented lesions of the conjunctiva in Carney's complex SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID MYXOMAS C1 NICHHD, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, C (reprint author), NICHHD, Dermatol Branch, NIH, 10 Ctr Dr MSC 1908,Bldg 10,12N238, Bethesda, MD 20892 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JAN PY 2000 VL 42 IS 1 BP 145 EP 145 DI 10.1016/S0190-9622(00)90027-6 PN 1 PG 1 WC Dermatology SC Dermatology GA 272VQ UT WOS:000084672000024 PM 10607338 ER PT J AU Lane, MA AF Lane, MA TI Metabolic mechanisms of longevity: Caloric restriction in mammals and longevity mutations in Caenorhabditis elegans; A common pathway?? SO JOURNAL OF THE AMERICAN AGING ASSOCIATION LA English DT Article ID LIFE-SPAN; INSULIN-RECEPTOR; PHOSPHOINOSITIDE 3-KINASE; SKELETAL-MUSCLE; OXIDATIVE DAMAGE; RHESUS-MONKEYS; FAMILY MEMBER; AGING RATS; C-ELEGANS; GENES AB Several recent studies in Caenorhabditis elegans have reported significant extension of the lifespan by probable loss of function mutations in various genes. When sequenced, many of these genes exhibited significant homology to genes in the mammalian insulin signaling cascade. For example, the daf-2 gene that has been shown to regulate lifespan in C elegans shares significant sequence homology with the insulin and IGF-1 receptor genes in mammals. Another longevity gene in the nematode, age- 1, is homologous with the p110 subunit of phosphatidylinositol 3-kinase in mammals. This enzyme functions early in the mammalian insulin response cascade to influence many important cellular growth and metabolic processes. These findings and others have led to the suggestion that lifespan regulation in nematodes is controlled by a mechanism similar to that involved in lifespan extension by caloric restriction in mammals. Many intriguing similarities exist between these two model systems providing some support for this idea. However, at present there is insufficient data to conclude that similar genes or mechanisms regulate lifespan determination in nematodes and in mammals. C1 NIA, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Lane, MA (reprint author), NIA, Intramural Res Program, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 59 TC 13 Z9 15 U1 0 U2 1 PU AMER AGING ASSOC PI MEDIA PA SALLY BALIN MEDICAL CENTER, 110 CHESLEY DR, MEDIA, PA 19063 USA SN 0161-9152 J9 J AM AGING ASSOC JI J. Am. Aging Assoc. PD JAN PY 2000 VL 23 IS 1 BP 1 EP 7 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 352AL UT WOS:000089192300001 PM 23604793 ER PT J AU Mattison, JA Wright, C Bronson, RT Roth, GS Ingram, DK Bartke, A AF Mattison, JA Wright, C Bronson, RT Roth, GS Ingram, DK Bartke, A TI Studies of aging in Ames dwarf mice: Effects of caloric restriction SO JOURNAL OF THE AMERICAN AGING ASSOCIATION LA English DT Article ID GROWTH FACTOR-I; DIETARY RESTRICTION; FOOD RESTRICTION; FISCHER-344 RATS; RHESUS-MONKEYS; INSULIN SENSITIVITY; BODY-TEMPERATURE; TRANSGENIC MICE; LIFE-SPAN; AGE AB Ames dwarf mice, which are small and deficient in growth homone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH) live much longer (1-1.25 years) than their normal siblings. It was of interest to examine the response of these animals to caloric restriction (CR) because of the possibility that dwarf mice are voluntarily caloric restricted. We are testing the hypothesis that this possible natural caloric restriction will negate any benefits of an imposed CR on lifespan. Male and female Ames dwarf mice and their normal counterparts have been fed ad libitum (AL) or a 30% CR diet for 25-29 months. Animals were monitored daily and weighed weekly. At 12-15 months of age, CR mice weighed significantly less than their AL fed counterparts (normal females: -42%, normal males: -23%, dwarf females: -18.8%, and dwarf males: -22.2%). Only in dwarf females has this significant difference disappeared with age. At one year of age, a comparison of daily food consumption revealed that female dwarf mice consume significantly more food per gram body weight than normal females and a similar tendency is evident for males. Although they received 30% less food, CR mice ate the same amount as AL mice per gram body weight. On measures of total locomotor activity, CR mice were significantly more active than their AL-fed counterparts. On an inhibitory avoidance learning task, 18-21 month old dwarf mice exhibited significantly better retention than their age- and diet-matched normal counterparts. Histopathological analysis in aging dwarf versus normal mice suggested that the incidence of tumors does not differ between the two groups but tumors appear to develop later in dwarf than in normal mice. After 2.25 years on the study 27% of AL normals, 52% of CR normals, 74% of AL dwarfs, and 87% of CR dwarfs are still alive. We conclude that Ames dwarfs are not CR mimetics although they share many characteristics. It remains to be determined whether CR will delay aging and cause a further life extension in Ames dwarf mice. C1 So Illinois Univ, Dept Physiol, Carbondale, IL 62901 USA. Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Mattison, JA (reprint author), So Illinois Univ, Dept Physiol, Carbondale, IL 62901 USA. RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X NR 43 TC 62 Z9 63 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 J AM AGING ASSOC JI J. Am. Aging Assoc. PD JAN PY 2000 VL 23 IS 1 BP 9 EP 16 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 352AL UT WOS:000089192300002 PM 23604794 ER PT J AU Slavkin, HC AF Slavkin, HC TI Health promotion made easy - Give a gift! SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID NEURAL-TUBE DEFECTS; FOLIC-ACID; PREVENTION; FOLATE; METABOLISM C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JAN PY 2000 VL 131 IS 1 BP 87 EP 91 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 273ZA UT WOS:000084738200022 PM 10649879 ER PT J AU Aronson, AR Bodenreider, O Chang, HF Humphrey, SM Mork, JG Nelson, SJ Rindflesch, TC Wilbur, WJ AF Aronson, AR Bodenreider, O Chang, HF Humphrey, SM Mork, JG Nelson, SJ Rindflesch, TC Wilbur, WJ TI The NLM Indexing Initiative SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc ID JOURNAL DESCRIPTORS AB The objective of NLM's Indexing Initiative (IND) is to investigate methods whereby automated indexing methods partially or completely substitute for current indexing practices. The project will be considered a success if methods can be designed and implemented that result in retrieval performance that is equal to or better than the retrieval performance of systems based principally on humanly assigned index terms. We describe the current state of the project and discuss If our plans for the future. C1 Natl Lib Med, LHNCBC, Bethesda, MD 20894 USA. Natl Lib Med, Div Lib Operat, Bethesda, MD 20894 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Aronson, AR (reprint author), Natl Lib Med, LHNCBC, Bethesda, MD 20894 USA. NR 16 TC 15 Z9 15 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 17 EP 21 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500005 ER PT J AU Bodenreider, O AF Bodenreider, O TI Using UMLS semantics for classification purposes SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc ID MEDICAL LANGUAGE SYSTEM AB The Unified Medical Language System (UMLS) contains semantic information about terms from various sources; each concept can be understood and located by its relationships to other concepts. We describe a method in which the semantic relationships between UMLS concepts are exploited for the purpose of classification. This method combines three existing components: I)Mapping terms to UMLS concepts; 2)Restricting UMLS concepts to MeSH; and 3) Mapping MeSH terms to disease categories. When applied to the automatic classification of condition terms into broad disease categories in the Clinical Trials, database, this method assigned relevant categories to 92% of the 1823 condition terms encountered. 135 (7%) failed to be classified and 14 ( .77%) were misclassified. The limits of this method are discussed, as well as the reuse of existing components, and the tuning required to achieve automatic classification. C1 Natl Lib Med, Bethesda, MD USA. RP Bodenreider, O (reprint author), Natl Lib Med, Bethesda, MD USA. NR 8 TC 6 Z9 6 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 86 EP 90 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500019 ER PT J AU Hole, WT Srinivasan, S AF Hole, WT Srinivasan, S TI Discovering missed synonymy in a large concept-oriented metathesaurus SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc AB The Unified Medical Language System (R) (UMLS (R)) [1, 2] Metathesuarus (R) is concept-oriented; its goal is to unite all names with identical meaning in a single Concept. The names come from its constituent vocabularies or "sources" - a wide variety of biomedical terminologies including many controlled vocabularies and classifications used in patient records, administrative health data, bibliographic, research, full-text, and expert systems. Many offer little definitional information, and many are not themselves concept-oriented, so identifying synonymy is a challenging semantic task [3]. The rapidly increasing size of the Metathesaurus makes the task daunting, demanding effective computational support; there are more than 1.5 million names for 730,000 concepts in the January 2000 release. Vocabularies are added and updated using sophisticated lexical matching, selective algorithms, and expert review [4, 5, 6]. Yet the result is imperfect; we have discovered and corrected missed synonymy in approximately 1% of previously released concepts each year. This paper reviews general methods for finding missed synonymy and describes several specific novel approaches which we have found effective. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Hole, WT (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 354 EP 358 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500073 ER PT J AU Rindflesch, TC Bean, CA Sneiderman, CA AF Rindflesch, TC Bean, CA Sneiderman, CA TI Argument identification for arterial branching predications asserted in cardiac catheterization reports SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CA SP Amer Med Informat Assoc AB The language describing coronary vasculature provides a suitable paradigm for research in semantic interpretation of anatomical text. As a pilot project we investigate the possibility of highly accurate retrieval of arterial branching relationships asserted in cardiac catheterization reports. Our methodology relies on the cooperation of underspecified linguistic analysis and structured domain knowledge. The satisfactory results of formal evaluation on both a training and testing set support the promise of this approach. C1 Natl Lib Med, Bethesda, MD 20894 USA. Univ Tennessee, Knoxville, TN 37996 USA. RP Natl Lib Med, Bethesda, MD 20894 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 704 EP 708 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500144 ER PT J AU Weeber, M Klein, H Aronson, AR Mork, JG de Jong-van den Berg, LTW Vos, R AF Weeber, M Klein, H Aronson, AR Mork, JG de Jong-van den Berg, LTW Vos, R TI Text-based discovery in biomedicine: The architecture of the DAD-system SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc ID FISH-OIL; CONNECTIONS; LITERATURES; RAYNAUDS AB Current scientific research takes place in highly specialized contexts with poor communication between disciplines as a likely consequence. Knowledge from one discipline may be useful for the other without researchers knowing it. As scientific publications area condensation of this knowledge, literature-based discovery tools may help the individual scientist to explore new useful domains. We report on the development of the DAD-system, a concept-based Natural Language Processing system for PubMed citations that provides the biomedical researcher such a tool. We describe the general architecture and illustrate its operation by a simulation of a well-known text-based discovery: The favorable effects of fish oil on patients suffering from Raynaud's disease [1]. C1 Univ Groningen, Inst Drug Explorat, Sch Pharm & Pharmacoepidemiol, Groningen, Netherlands. Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. Univ Maastricht, Fac Hlth Sci, Maastricht, Netherlands. RP Weeber, M (reprint author), Univ Groningen, Inst Drug Explorat, Sch Pharm & Pharmacoepidemiol, Groningen, Netherlands. NR 16 TC 13 Z9 15 U1 0 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 903 EP 907 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500184 ER PT J AU Wilbur, WJ AF Wilbur, WJ TI Boosting nai ve Bayesian learning on a large subset of MEDLINE (R) SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 04-08, 2000 CL LOS ANGELES, CALIFORNIA SP Amer Med Informat Assoc AB We are concerned with the rating of new documents that appear in a large database (MEDLINE) and are candidates for inclusion in a small specialty database (REBASE (R). The requirement is to rank the new documents as nearly in order of decreasing potential to be added to the smaller database as possible, so as to improve the coverage of the smaller database without increasing the effort of those who manage this specialty database. To perform this ranking task we have considered several machine learning approaches based on the not ve Bayesian algorithm. We find that adaptive boosting outperforms nai ve Bayes, but that a new form of boosting which we term staged Bayesian retrieval outperforms adaptive boosting. Staged Bayesian retrieval involves two stages of Bayesian retrieval and we further end that if the second stage is replaced by a support vector machine we again obtain a significant improvement over the strictly Bayesian approach. C1 Natl Lib Med, NCBI, Bethesda, MD 20894 USA. RP Wilbur, WJ (reprint author), Natl Lib Med, NCBI, Bethesda, MD 20894 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 918 EP 922 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500187 ER PT J AU Bodenreider, O AF Bodenreider, O TI A semantic navigation tool for the UMLS SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD 20894 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 971 EP 971 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500223 ER PT J AU Chang, HF Nelson, SJ AF Chang, HF Nelson, SJ TI An interoperable disease description database SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD 20894 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 979 EP 979 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500231 ER PT J AU Divita, G Browne, AC Tse, T Cheh, ML Loane, RF Abramson, M AF Divita, G Browne, AC Tse, T Cheh, ML Loane, RF Abramson, M TI A spelling suggestion technique for terminology servers SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 994 EP 994 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500246 ER PT J AU Marcelo, AB AF Marcelo, AB TI A comparison of open source electronic medical records systems SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1078 EP 1078 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500329 ER PT J AU Marcelo, AB AF Marcelo, AB TI Developing healthcare applications using Common Open Source Medical Objects (COSMOS) SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1079 EP 1079 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500330 ER PT J AU Roth, L Hole, WT AF Roth, L Hole, WT TI Managing name ambiguity in the UMELS Metathesaurus SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1124 EP 1124 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500375 ER PT J AU Shin, D AF Shin, D TI XML information retrieval mapped to hybrid storage model SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Natl Lib Med, Bethesda, MD 20894 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 2000 SU S BP 1137 EP 1137 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RC UT WOS:000170207500388 ER PT J AU Banwell, M Edwards, A Smith, J Hamel, E Verdier-Pinard, P AF Banwell, M Edwards, A Smith, J Hamel, E Verdier-Pinard, P TI Convergent synthesis and preliminary biological evaluation of (+/-)-B-norrhazinal SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID RHAZINILAM; TUBULIN; BIPHENYLS AB The title compound 3, an analogue of the naturally-derived spindle toxin rhazinilam (1), has been synthesised, characterised crystallographically and subjected to a preliminary biological evaluation. C1 Australian Natl Univ, Inst Adv Studies, Res Sch Chem, Canberra, ACT 0200, Australia. NCI, Screening Technol Branch, Dev Therapeut Program,Div Canc Treatmen & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Banwell, M (reprint author), Australian Natl Univ, Inst Adv Studies, Res Sch Chem, Canberra, ACT 0200, Australia. RI smith, jason/J-7391-2014; Banwell, Martin/H-8354-2014 OI smith, jason/0000-0001-6313-3298; NR 23 TC 17 Z9 17 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1472-7781 J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PY 2000 IS 10 BP 1497 EP 1499 DI 10.1039/b001731k PG 3 WC Chemistry, Organic SC Chemistry GA 319BF UT WOS:000087318600004 ER PT J AU Dunson, DB AF Dunson, DB TI Bayesian latent variable models for clustered mixed outcomes SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE Gibbs sampler; mixture model; multihit model; multiple outcomes; reproductive applications ID SAMPLING-BASED APPROACH; RESPONSE MODELS; MARKOV-CHAINS; DISCRETE; BINARY AB A general framework is proposed for modelling clustered mixed outcomes. A mixture of generalized linear models is used to describe the joint distribution of a set of underlying variables, and an arbitrary function relates the underlying variables to the observed outcomes. The model accommodates multilevel data structures, general covariate effects and distinct link functions and error distributions for each underlying variable. Within the framework proposed, novel models are developed for clustered multiple binary, unordered categorical and joint discrete and continuous outcomes. A Markov chain Monte Carlo sampling algorithm is described for estimating the posterior distributions of the parameters and latent variables. Because of the flexibility of the modelling framework and estimation procedure, extensions to ordered categorical outcomes and more complex data structures are straightforward. The methods are illustrated by using data from a reproductive toxicity study. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 136 Z9 137 U1 2 U2 11 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2000 VL 62 BP 355 EP 366 DI 10.1111/1467-9868.00236 PN 2 PG 12 WC Statistics & Probability SC Mathematics GA 303QM UT WOS:000086433600009 ER PT J AU Dunson, DB AF Dunson, DB TI Models for papilloma multiplicity and regression: applications to transgenic mouse studies SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE EM algorithm; latent variables; skin painting studies; transition models; tumorigenicity ID MICE; SKIN; LIKELIHOOD AB In cancer studies that use transgenic or knockout mice, skin tumour counts are recorded over time to measure tumorigenicity. In these studies cancer biologists are interested in the effect of endogenous and/or exogenous factors on papilloma onset, multiplicity and regression. In this paper an analysis of data from a study conducted by the National Institute of Environmental Health Sciences on the effect of genetic factors on skin tumorigenesis is presented. Papilloma multiplicity and regression are modelled by using Bernoulli, Poisson and binomial latent variables, each of which can depend on covariates and previous outcomes. An EM algorithm is proposed for parameter estimation, and generalized estimating equations adjust for extra dependence between outcomes within individual animals. A Cox proportional hazards model is used to describe covariate effects on the onset of tumours. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233,MD A3-03, Res Triangle Pk, NC 27709 USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2000 VL 49 BP 19 EP 30 DI 10.1111/1467-9876.00176 PN 1 PG 12 WC Statistics & Probability SC Mathematics GA 284UP UT WOS:000085351200002 ER PT J AU Dunson, DB AF Dunson, DB TI Models for papilloma multiplicity and regression: applications to transgenic mouse studies (vol 49, pg 19, 2000) SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Correction C1 Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2000 VL 49 BP 421 EP 421 DI 10.1111/1467-9876.00202 PN 3 PG 1 WC Statistics & Probability SC Mathematics GA 336HG UT WOS:000088295400010 ER PT J AU Korach, KS AF Korach, KS TI Estrogen receptor knock-out mice: Molecular and endocrine phenotypes SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 10-13, 1999 CL ATLANTA, GEORGIA SP Soc Gynecol Invest DE estrogen receptor knock-out mice; alpha ERKO; beta ERKO; transgenic mice; estrogen receptor alpha and beta; gene-targeting techniques ID DISRUPTION; GENE AB Using gene-targeting techniques, transgenic, knock-out (KO) mice, homozygous for the disrupted estrogen receptor alpha (alpha ERKO) and beta gene (beta ERKO) have been produced. Estrogen receptor (ER) beta expression does not appear to be dependent on ER alpha expression. Progesterone receptor (PR) mRNA is detected in alpha ERKO mice and appears to have both estrogen-independent and -dependent gene regulation. The phenotypic differences in alpha ERKO and beta ERKO mice are described. Additional studies will further define the specific roles of ER alpha and ER beta in various tissues. (J Soc Gynecol Investig 2000;7:S16-7) Copyright (C) 2000 by the Society for Gynecologic Investigation. C1 NIEHS, Environm Dis Med Program, NIH, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, Environm Dis Med Program, NIH, POB 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 6 TC 30 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD JAN-FEB PY 2000 VL 7 IS 1 SU S BP S16 EP S17 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 294CP UT WOS:000085892600006 PM 10732323 ER PT J AU Ginsburg, A AF Ginsburg, A TI Reversible, thermally induced domain unfolding in oligomeric proteins - Spectral and DSC measurements SO JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY LA English DT Article; Proceedings Paper CT XXth Italian Calorimetry Thermal Analysis and Experimental Thermodynamics Conference CY 1999 CL ROME, ITALY DE Acanthamoeba myosin II rod coiled-coil; amino terminal domain of enzyme I of the phosphoenolpyruvate : sugar phosphotransferase system of E. coli; circular dichroism; differential scanning calorimetry; dodecameric glutamine synthetase; oligomeric protein domains; thermal unfolding; UV-spectra ID ACANTHAMOEBA MYOSIN-II; DODECAMERIC GLUTAMINE-SYNTHETASE; SUGAR PHOSPHOTRANSFERASE SYSTEM; ESCHERICHIA-COLI PHOSPHOENOLPYRUVATE; DIFFERENTIAL SCANNING CALORIMETRY; N-TERMINAL DOMAIN; STATISTICAL MECHANICAL DECONVOLUTION; SKELETAL-MUSCLE MYOSIN; AMINO-ACID-SEQUENCE; ENZYME-I AB Spectral and differential scanning calorimetry (DSC) results for three oligomeric proteins are briefly reviewed. (A) Reversible, thermally-induced partial unfolding reactions in dodecameric glutamine synthetase from E. coli involve cooperative, two two-state transitions of subunits and demonstrate communication among subunits. (B) Thermal unfolding of intact Acanthamoeba myosin II is more cooperative than that of mammalian skeletal muscle myosin. Nucleotide-induced conformational changes thermally stabilize head domains in both myosins. The long dimeric coiled-coil rod of Acanthamoeba myosin II undergoes a reversible, cooperative, single two-state thermal transition with concomitant chain dissociation. (C) The amino terminal domain of enzyme I of the E. coli PEP:sugar phosphotransferase system is destabilized by phosphorylation of the active-site His 189. C1 NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Ginsburg, A (reprint author), NHLBI, Sect Prot Chem, Biochem Lab, NIH, Bldg 3,Room 208, Bethesda, MD 20892 USA. NR 50 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1418-2874 J9 J THERM ANAL CALORIM JI J. Therm. Anal. PY 2000 VL 61 IS 2 BP 425 EP 436 DI 10.1023/A:1010113300190 PG 12 WC Thermodynamics; Chemistry, Analytical; Chemistry, Physical SC Thermodynamics; Chemistry GA 351CB UT WOS:000089137500010 ER PT J AU Naughton, CK Ornstein, DK Smith, DS Catalona, WJ AF Naughton, CK Ornstein, DK Smith, DS Catalona, WJ TI Pain and morbidity of transrectal ultrasound guided prostate biopsy: A prospective randomized trial of 6 versus 12 cores SO JOURNAL OF UROLOGY LA English DT Article DE biopsy, needle; morbidity; diagnosis; prostatic neoplasms ID CANCER; COMPLICATIONS; ACCEPTANCE AB Purpose: An increasing number of studies suggest that 6-sector transrectal ultrasound guided biopsy of the prostate provides insufficient material to detect all clinically important prostate cancers and more cores may improve detection rates. We performed a prospective, randomized study to determine the effect of increasing the number of cores from 6 to 12 on pain and other morbidity associated with the biopsy procedure. Materials and Methods: A total of 160 men (44 black, 28%) with a mean age plus or minus standard deviation of 65 +/- 8 years who had serum prostate specific antigen between 2.5 and 20.0 ng./ml, and/or digital rectal examination findings suspicious for cancer were prospectively randomized to undergo 6 or 12-core biopsy. Patients completed a self-administered questionnaire addressing pain and other morbidity before, and immediately and 2 and 4 weeks after biopsy. Results: There was no difference between groups in mean pain scale with time for abdominal and rectal pain. For probe insertion, needle insertion and overall pain there was a significant increase in pain recalled at 2 which persisted at 4 weeks compared to immediately after biopsy. However, there was no difference for these 3 post-biopsy pain measures between the 6 and la-core groups. In the 12-core group there was a statistically significant increase in hematochezia and hematospermia (24% versus 10%, p = 0.04 and 89% versus 71%, p = 0.01, respectively) but no significant difference between groups reporting morbidity as a moderate or major problem. There was no significant change in International Prostate Symptom Score, fever or hospitalization in the 12-core group. Conclusions: The 12-core prostate biopsy procedure is generally well tolerated and can be safely performed with no significant difference in pain or morbidity compared to the B-core procedure. C1 Washington Univ, Sch Med, Dept Surg, Div Urol, St Louis, MO 63110 USA. NCI, Urol Oncol Div, Bethesda, MD 20892 USA. RP Naughton, CK (reprint author), Washington Univ, Sch Med, Dept Surg, Div Urol, 4960 Childrens Pl, St Louis, MO 63110 USA. NR 13 TC 110 Z9 117 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2000 VL 163 IS 1 BP 168 EP 171 DI 10.1016/S0022-5347(05)67996-7 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 266XE UT WOS:000084324900049 PM 10604338 ER PT J AU Peeples, ME Collins, PL AF Peeples, ME Collins, PL TI Mutations in the 5 ' trailer region of a respiratory syncytial virus minigenome which limit RNA replication to one step SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTION ELONGATION-FACTOR; MESSENGER-RNA; SENDAI VIRUS; N-PROTEIN; TERMINAL COMPLEMENTARITY; GENOME REPLICATION; GENE-START; EXPRESSION; POLYMERASE; SEQUENCE AB The 3' termini of the genomic and antigenomic RNAs of human respiratory syncytial virus (RSV) are identical at 10 of the first 11 nucleotide positions and 21 of the first 26 positions. These consented S'-terminal sequences are thought to contain the genomic and antigenomic promoters. Furthermore, the complement of each conserved sequence (i.e., the 5' end of the RNA it encodes) might contain an encapsidation signal. Using an RSV minigenome system, we individually mutated each of the last seven nucleotides in the 5' trailer region of the genome. We analyzed effects of these mutations on encapsidation of the T7 polymerase-transcribed negative-sense genome, its ability to function as a template for RSV-driven synthesis of positive-sense anti-genome and mRNA, and the ability of this antigenome to be encapsidated and to function as template for the synthesis of more genome. As a technical complication, mutations in the last five nucleotides of the trailer region were found to affect the efficiency of the adjoining T7 promoter over more than a 10-fold range, even though three nonviral G residues had been included between the core promoter and the trailer to maximize the efficiency of promoter activity, This was controlled in all experiments by monitoring the levels of total and encapsidated genome. The efficiency of encapsidation of the T7 polymerase-transcribed genome was not affected by any of the trailer mutations. Furthermore, neither the efficiency of positive-sense RNA synthesis from the genome nor the efficiency of encapsidation of the encoded antigenome was affected by the mutations. However, nucleotide substitution at positions 2, 3, 6, or 7 relative to the 5' end of the trailer blocked the production of progeny genome, whereas substitution at positions 1 and 5 allowed a low level of genome production and substitutions at position 4 were tolerated. Position 4 is the only one of the seven positions examined that is not conserved between the 3' ends of genomic and antigenomic RNA. The mutations that blocked the synthesis of progeny genome thus limited RNA replication to one step, namely, the synthesis and encapsidation of antigenome. Restoration of terminal complementarity for one of the trailer mutants by making a compensatory mutation in the leader region did not restore synthesis of genomic RNA, confirming that its loss was not due to reduced terminal complementarity. Interestingly, this leader mutation appeared to prevent antigenome synthesis with only a slight effect on mRNA synthesis, apparently providing a dissociation between these two synthetic activities, Genomes in which the terminal 24 or 325 nucleotides of the trailer have been deleted were competent fur encapsidation and the synthesis of mRNA and antigenomic RNA, further confirming that terminal complementarity was not required fur these functions. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 26 TC 43 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 1 BP 146 EP 155 PG 10 WC Virology SC Virology GA 263QQ UT WOS:000084137100018 PM 10590101 ER PT J AU Halvas, EK Svarovskaia, ES Pathak, VK AF Halvas, EK Svarovskaia, ES Pathak, VK TI Development of an in vivo assay to identify structural determinants in murine leukemia virus reverse transcriptase important for fidelity SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVATING RETROVIRAL VECTORS; NUCLEIC ACID INTERACTIONS; SINGLE REPLICATION CYCLE; HIGH-LEVEL RESISTANCE; DOUBLE-STRANDED DNA; RNASE-H-DOMAIN; MISPAIR EXTENSION; MUTATION-RATE; IN-VIVO AB Error-prone DNA synthesis by retroviral reverse transcriptases (RTs) is a major contributor to variation in retroviral populations. Structural features of retroviral RTs that are important fur accuracy of DNA Synthesis in vivo are not known. To identify structural elements of murine leukemia virus (MLV) RT important for fidelity in vivo, we developed a D17-based encapsidating cell line (ANGIE P) which is designed to express the amphotropic MLV envelope. ANGIE: P also contains an MLV-based retroviral vector (GA-1) which encodes a wild-type bacterial beta-galactosidase gene (lacZ) and a neomycin phosphotransferase gene. Transfection of ANGIE P cells with wild-type or mutated MLV gag-pol expression constructs generated GA-1 virus that was able to undergo only one cycle of viral replication upon infection of D17 cells. The infected D17 cell clones were characterized by staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal), and the frequencies of inactivating mutations in lacZ were quantified. Three mutations in the YVDD motif (V223M, V223S, and V223A) and two mutations in the RNase H domain (S526A and R657S) exhibited frequencies of lacZ inactivation 1.2- to 2.3-fold higher than that for the wild-type MLV RT (P < 0.005). Two mutations (V223I and Y598V) did not affect the frequency of lacZ inactivation. These results establish a sensitive in vivo assay for identification of structural determinants important for accuracy of DNA synthesis and indicate that several structural determinants may have an effect on the in vivo fidelity of MLV RT. C1 W Virginia Univ, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. W Virginia Univ, Dept Biochem, Morgantown, WV 26506 USA. RP Pathak, VK (reprint author), NCI, Frederick Canc Res & Dev Ctr, HIV Drug Resistance Program, DBS, Bldg 535,Rm 334, Frederick, MD 21702 USA. FU NCI NIH HHS [CA58875] NR 66 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 1 BP 312 EP 319 PG 8 WC Virology SC Virology GA 263QQ UT WOS:000084137100036 PM 10590119 ER PT J AU Salzwedel, K Smith, ED Dey, B Berger, EA AF Salzwedel, K Smith, ED Dey, B Berger, EA TI Sequential CD4-coreceptor interactions in human immunodeficiency virus type 1 Env function: Soluble CD4 activates Env for coreceptor-dependent fusion and reveals blocking activities of antibodies against cryptic conserved epitopes on gp120 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN CELL-LINES; ENVELOPE GLYCOPROTEIN; CHEMOKINE RECEPTOR; MONOCLONAL-ANTIBODIES; VACCINIA VIRUS; HIV GP120; CD4-INDEPENDENT INFECTION; ANTIGENIC VARIATION; VIRAL ENTRY; SUBTYPE-A AB We devised an experimental system to examine sequential events by which the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) interacts with CD4 and coreceptor to induce membrane fusion. Recombinant soluble CD4 (sCD4) activated fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) but lacking CD4. sCD4-activated fusion was dose dependent, occurred comparably with two- and four-domain proteins, and demonstrated Env-coreceptor specificities parallel to those reported in conventional fusion and infectivity systems. Fusion activation occurred upon sCD4 preincubation and washing of the Env-expressing effector cells but not the coreceptor-bearing target cells, thereby demonstrating that sCD4 exerts its effects by acting on Env. These findings provide direct functional evidence for a sequential two-step model of Env-receptor interactions, whereby gp120 binds first to CD4 and becomes activated for subsequent functional interaction with coreceptor, leading to membrane fusion. We used the sCD4-activated system to explore neutralization by the anti-gp120 human monoclonal antibodies 17b and 48d. These antibodies reportedly bind conserved CD4-induced epitopes involved in coreceptor interactions but neutralize HIV-1 infection only weakly. We found that 17b and 48d had minimal effects in the standard cell fusion system using target cells expressing both CD4 and coreceptor but potently blocked sCD4-activated fusion with target cells expressing coreceptor alone. Both antibodies strongly inhibited sCD4-activated fusion by Ems from genetically diverse HIV-1 isolates. Thus, the sCD4-activated system reveals conserved Env-blocking epitopes that are masked in native Env and hence not readily detected by conventional systems. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 236, Bethesda, MD 20892 USA. NR 61 TC 119 Z9 124 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 1 BP 326 EP 333 PG 8 WC Virology SC Virology GA 263QQ UT WOS:000084137100038 PM 10590121 ER PT J AU Askovic, S McAtee, FJ Favara, C Portis, JL AF Askovic, S McAtee, FJ Favara, C Portis, JL TI Brain infection by neuroinvasive but avirulent murine oncornaviruses SO JOURNAL OF VIROLOGY LA English DT Article ID AMINO-ACID TRANSPORTER; CELL-SURFACE RECEPTOR; INDUCED SPONGIFORM NEURODEGENERATION; LEUKEMIA-VIRUS PVC-211; MOTOR NEURON DISEASE; INCUBATION PERIOD; NEUROLOGIC DISEASE; NEUROTROPIC RETROVIRUS; ECOTROPIC RETROVIRUS; HIPPOCAMPAL-NEURONS AB The chimeric murine oncornavirus FrCas(E) causes a rapidly progressive noninflammatory spongiform encephalomyelopathy after neonatal inoculation. The virus was constructed by the introduction of pol-env sequences from the wild mouse virus CasBrE into the genome of a neuroinvasive but nonneurovirulent strain of Friend murine leukemia virus (FMuLV), FB29. Although the brain infection by FrCasE as well as that by other neurovirulent murine retroviruses has been described in detail, little attention has been paid to the neuroinvasive but nonneurovirulent viruses. The purpose of the present study was to compare brain infection by FrCasE with that by FB29 and another nonneurovirulent virus, F43, which contains pol-env sequences from FMuLV 57. Both FB29 and F43 infected the same spectrum of cell types in the brain as that infected by FrCasE, including endothelial cells, microglia, and populations of neurons which divide postnatally. Viral burdens achieved by the two nonneurovirulent viruses in the brain were actually higher than that of FrCasE. The widespread infection of microglia by the two nonneurovirulent viruses is notable because it is infection of these cells by FrCasE which is thought to be a critical determinant of its neuropathogenicity. These results indicate that although the sequence of the envelope gene determines neurovirulence, this effect appears to operate through a mechanism which does not influence either viral tropism or viral burden in the brain. Although all three viruses exhibited similar tropism for granule neurons in the cerebellar cortex, there was a striking difference in the distribution of envelope proteins in those cells in vivo. The FrCas(E) envelope protein accumulated in terminal axons, whereas those of FB29 and F43 remained predominantly in the cell bodies. These observations suggest that differences in the intracellular sorting of these proteins may exist and that these differences appear to correlate with neurovirulence. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Askovic, S (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 South 4th St, Hamilton, MT 59840 USA. NR 47 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 1 BP 465 EP 473 PG 9 WC Virology SC Virology GA 263QQ UT WOS:000084137100053 PM 10590136 ER PT J AU Kashanchi, F Agbottah, ET Pise-Masison, CA Mahieux, R Duvall, J Kumar, A Brady, JN AF Kashanchi, F Agbottah, ET Pise-Masison, CA Mahieux, R Duvall, J Kumar, A Brady, JN TI Cell cycle-regulated transcription by the human immunodeficiency virus type 1 Tat transactivator SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-POLYMERASE-II; C-TERMINAL DOMAIN; ACTIVATION-RESPONSIVE REGION; FACTOR P-TEFB; HIV-1 TAT; IN-VITRO; GENE-EXPRESSION; VPR GENE; T-CELLS; DEPENDENT TRANSCRIPTION AB Cyclin-dependent kinases are required for the Tat-dependent transition from abortive to productive elongation. Further, the human immunodeficiency virus type 1 (HIV-1) Vpr protein prevents proliferation of infected cells by arresting them in the G(2) phase of the cell cycle. These findings suggest that the life cycle of the virus may be integrally related to the cell cycle. We now demonstrate by in vitro transcription analysis that Tat-dependent transcription takes place in a cell cycle-dependent manner. Remarkably, Tat activates gene expression in two distinct stages of the cell cycle. Tat-dependent long terminal repeat activation is observed in G(1). This activation is TAR dependent and requires a functional Sp1 binding site. A second phase of transactivation by Tat is observed in G(2) and is TAR independent. This later phase of transcription is enhanced by a natural cell cycle blocker of HIV-1, vpr, which arrests infected cells at the G(2)/M boundary. These studies link the HIV-1 Tat protein to cell cycle-specific biological functions. C1 NIH, NCI, Virus Tumor Biol Sect, LRGBE, Bethesda, MD 20892 USA. George Washington Univ, Dept Biochem, Washington, DC USA. RP Brady, JN (reprint author), NIH, NCI, Virus Tumor Biol Sect, LRGBE, Bldg 41,Room B201, Bethesda, MD 20892 USA. EM bradyj@exchange.nih.gov NR 92 TC 45 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 2 BP 652 EP 660 DI 10.1128/JVI.74.2.652-660.2000 PG 9 WC Virology SC Virology GA 268ND UT WOS:000084421700007 PM 10623726 ER PT J AU Race, R Oldstone, M Chesebro, B AF Race, R Oldstone, M Chesebro, B TI Entry versus blockade of brain infection following oral or intraperitoneal scrapie administration: Role of prion protein expression in peripheral nerves and spleen SO JOURNAL OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; PRP KNOCKOUT MICE; SPONGIFORM ENCEPHALOPATHIES; LYMPHORETICULAR-SYSTEM; HAMSTER SCRAPIE; B-LYMPHOCYTES; MOUSE SCRAPIE; AGENT; PATHOGENESIS; RESISTANT AB Naturally occurring transmissible spongiform encephalopathy (TSE) diseases such as bovine spongiform encephalopathy in cattle are probably transmitted by oral or other peripheral routes of infection. While prion protein (PrP) is required for susceptibility, the mechanism of spread of infection to the brain is not clear. Two prominent possibilities include hematogenous spread by leukocytes and neural spread by axonal transport. In the present experiments, following oral or intraperitoneal infection of transgenic mice with hamster scrapie strain 263K, hamster PrP expression in peripheral nerves was sufficient for successful infection of the brain, and cells of the spleen were not required either as a site of amplification or as transporters of infectivity. The role of tissue-specific PrP expression of foreign PrP in interference with scrapie infection was also studied in these transgenic mice. Peripheral expression of heterologous PrP completely protected the majority of mice from clinical disease after oral or intraperitoneal scrapie infection. Such extensive protection has not been seen in earlier studies on interference, and these results suggested that gene therapy with mutant PrP may be effective in preventing TSE diseases. C1 NIH, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. Scripps Res Inst, Div Virol, Dept Neuropharmacol, La Jolla, CA 92037 USA. RP Chesebro, B (reprint author), NIH, Persistent Viral Dis Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM bchesebro@nih.gov FU NIA NIH HHS [AG04342, P01 AG004342] NR 44 TC 138 Z9 139 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 2 BP 828 EP 833 DI 10.1128/JVI.74.2.828-833.2000 PG 6 WC Virology SC Virology GA 268ND UT WOS:000084421700026 PM 10623745 ER PT J AU Imamichi, T Sinha, T Imamichi, H Zhang, YM Metcalf, JA Falloon, J Lane, HC AF Imamichi, T Sinha, T Imamichi, H Zhang, YM Metcalf, JA Falloon, J Lane, HC TI High-level resistance to 3 '-azido-3 '-deoxythimidine due to a deletion in the reverse transcriptase gene of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; PROTEASE INHIBITOR; DRUG-RESISTANCE; ZIDOVUDINE AZT; NONNUCLEOSIDE INHIBITOR; COMBINATION THERAPY; POL GENE; MUTATIONS; REPLICATION AB A variant of human immunodeficiency virus type 1 (HIV-1) possessing a deletion in the reverse transcriptase (RT) gene at codon 67 was identified in a patient who had failed combination antiretroviral therapy. This deletion initially emerged under the selective pressure of combination therapy with 3'-azido-3'-deoxythymidine (AZT) plus 2',3'-dideoxyinosine. It has persisted for more than 3 years in association with the accumulation of a variety of other well-described drug resistance mutations and an uncharacterized mutation at RT codon 69 (T69G). Phenotypic studies demonstrated that the codon 67 deletion by itself had little effect on AZT sensitivity. However, in the context of the T69G mutation and three other mutations known to be associated with AZT resistance (K70R, T215F, and K219Q), this deletion led to a increase in AZT resistance from 8.5-fold to 145-fold. A further increase in resistance (up to 1,813-fold) was observed when two mutations associated with nonnucleoside RT inhibitor resistance (K103N and L7-1I) were added to the deletion T69G K70R T215F K219Q construct. Hence, these results establish that a deletion at RT codon 67 may be selected for in the presence of antiretroviral therapy and may lead to high-level resistance to AZT. C1 NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Lane, HC (reprint author), NIAID, Immunoregulat Lab, 10 Ctr Dr,Rm 11S231, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 52 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2000 VL 74 IS 2 BP 1023 EP 1028 DI 10.1128/JVI.74.2.1023-1028.2000 PG 6 WC Virology SC Virology GA 268ND UT WOS:000084421700049 PM 10623768 ER PT J AU Carmelli, D Kelly-Hayes, M Wolf, PA Swan, GE Jack, LM Reed, T Guralnik, JM AF Carmelli, D Kelly-Hayes, M Wolf, PA Swan, GE Jack, LM Reed, T Guralnik, JM TI The contribution of genetic influences to measures of lower-extremity function in older male twins SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PHYSICAL PERFORMANCE; NHLBI TWIN; RISK-FACTORS; DISABILITY; CONCORDANCE; DISEASE; FRAILTY AB Tests of balance, gait and endurance were administered to 95 monozygotic: (MZ) and 92 dizygotic (DZ), white male twins aged 68 to 79 years who had been born in the United States. Within-twin-pair correlations were calculated for each individual task and for an overall summary performance score. These were subjected to structural equation modeling to determine the contributions of genetic and environmental influences to individual differences in performance scores. MZ intraclass correlations were significant and greater than DZ correlations for the g-foot walk and the repeated chair stands task, but not for the standing balance task. The heritability of the lower-extremity summary score was 57%, of which 39% was due to additive genetic effects and 18% due to nonadditive effects. In addition, we found that genetic influences contributed primarily to twin similarity in the poorest quartile of performance, whereas shared environmental influences contributed to twin similarity in the best quartile. C1 SRI Int, Ctr Hlth Sci, Menlo Park, CA 94025 USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. Indiana Univ, Sch Med, Dept Med Genet, Indianapolis, IN 46202 USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Carmelli, D (reprint author), SRI Int, Ctr Hlth Sci, 333 Ravenswood Ave, Menlo Park, CA 94025 USA. FU NHLBI NIH HHS [HL51429] NR 20 TC 42 Z9 43 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2000 VL 55 IS 1 BP B49 EP B53 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XN UT WOS:000088044100009 PM 10719763 ER PT J AU Ghezzi, EM Wagner-Lange, LA Schork, MA Metter, EJ Baum, BJ Streckfus, CF Ship, JA AF Ghezzi, EM Wagner-Lange, LA Schork, MA Metter, EJ Baum, BJ Streckfus, CF Ship, JA TI Longitudinal influence of age, menopause, hormone replacement therapy, and other medications on parotid flow rates in healthy women SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID SALIVARY-GLAND FUNCTION; ORAL DISCOMFORT; POSTMENOPAUSAL WOMEN; DRY MOUTH; INDIVIDUALS; WHOLE AB Background. Recent investigations have demonstrated that parotid salivary dysfunction is not a normal process of aging, bur may be the consequence of systemic conditions and their treatment, including medications and menopause. The purpose of this study was to assess longitudinally the influence of age, menopausal status, hormone replacement therapy, and other medications on stimulated parotid flow rates (SPFRs) in healthy women. Methods. Medical diagnoses, menopausal status, medication utilization, and 2% citric acid stimulated parotid salivas were collected from 396 women, aged 21 to 96 years, from the Baltimore Longitudinal Study of Aging (National Institute on Aging, National Institutes of Health) over a 17-year span by three investigators. Results. There was no overall longitudinal effect of time on SPFR. Age at first visit was a significant predictor of a decrease in SPFR when adjusted for time and xerostomic medications. However, the deleterious effect of taking one xerostomic medication was equivalent to approximately 14 years of aging. Menopausal status and hormone replacement therapy were not consistently associated with diminished SPFR. Conclusions. These results suggest that menopause and hormone replacement therapy are not associated with parotid salivary dysfunction. Aging may have a statistically significant yet small deleterious influence on SPFR; however, the adverse influence of xerostomic medications is much larger. C1 Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Natl Inst Dental & Craniofacial Res, NIH, Bethesda, MD USA. Univ Mississippi, Sch Dent, Jackson, MS 39216 USA. RP Ship, JA (reprint author), Univ Michigan, Sch Dent, 1011 N Univ,Room G-004, Ann Arbor, MI 48109 USA. FU BHP HRSA HHS [D31-AH90005-01] NR 45 TC 24 Z9 24 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2000 VL 55 IS 1 BP M34 EP M42 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 331XN UT WOS:000088044100017 PM 10719771 ER PT J AU Leveille, SG Penninx, BWJH Melzer, D Izmirlian, G Guralnik, JM AF Leveille, SG Penninx, BWJH Melzer, D Izmirlian, G Guralnik, JM TI Sex differences in the prevalence of mobility disability in old age: The dynamics of incidence, recovery, and mortality SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article; Proceedings Paper CT 51st Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 20-24, 1998 CL PHILADELPHIA, PENNSYLVANIA SP Gerontol Soc Amer ID ACTIVE LIFE EXPECTANCY; UNITED-STATES; MAINTAINING MOBILITY; DISABLEMENT PROCESS; PHYSICAL FUNCTION; ALAMEDA COUNTY; RECENT TRENDS; HEALTH-STATUS; POPULATION; GENDER AB Objectives. This study examined sex differences in the prevalence of mobility disability in older adults according to the influences of three components of prevalence: disability incidence, recovery from disability, and mortality. Methods. Participants in a population-based study of older adults from three communities in the United States (N = 10,263) were studied for up to 7 years. Life table methods were used to estimate the influence of each of the three components of disability prevalence in women and men. Sex differences in probabilities for transition states were measured by relative risks derived from a single model using a Markov chain approach. Results. The proportion of disabled women increased from 22% of women aged 70 years to 81% of those aged 90 years. In men, comparable figures were 15% and 57%. Incidence had the greatest impact on the sex differences in disability prevalence until age 90 and older when recovery rates had a greater impact on differences in prevalence. Mortality differences in men and women had only a modest impact on sex differences in disability prevalence. These findings initially seemed to contradict striking sex differences observed in the relative risks for mortality in men compared with women. Subsequent graphical analyses showed that incidence rather than recovery or mortality largely accounted for sex differences in disability prevalence in old age. Conclusion. Disability incidence, recovery from disability and mortality dynamically influence the sex differences in the prevalence of mobility disability. However, incidence has the greatest impact overall on the higher prevalence of disability in women compared with men. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Inst Res Extramural Med, NL-1081 HV Amsterdam, Netherlands. RP Leveille, SG (reprint author), Hebrew Rehabil Ctr Aged, Res & Trading Inst, 1200 Ctr St, Boston, MA 02131 USA. NR 30 TC 142 Z9 142 U1 0 U2 7 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JAN PY 2000 VL 55 IS 1 BP S41 EP S50 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 331YA UT WOS:000088045200011 PM 10728129 ER PT J AU Ojo, AO Hanson, JA Wolfe, RA Leichtman, AB Agodoa, LY Port, FK AF Ojo, AO Hanson, JA Wolfe, RA Leichtman, AB Agodoa, LY Port, FK TI Long-term survival in renal transplant recipients with graft function SO KIDNEY INTERNATIONAL LA English DT Article DE graft loss; end-stage renal disease; kidney transplant; posttransplant mortality risks; and renal transplant survival ID KIDNEY-TRANSPLANTATION; FOLLOW-UP; CADAVERIC TRANSPLANTATION; PATIENT SURVIVAL; MORTALITY RISK; DEATH; DISEASE; DIALYSIS; FAILURE; HEMODIALYSIS AB Background Death with graft function (DWGF) is a common cause of graft loss. The risks and determinants of DWGF have not been studied in a recent cohort of renal transplant recipients. We performed a population-based survival analysis of U.S. patients with end-stage renal disease (ESRD) transplanted between 1988 and 1997. Methods. Registry data were used to evaluate long-term patient survival and cause-specific risks of DWGF in 86,502 adult (greater than or equal to 18 years) renal transplant recipients. Results. Out of 18,482 deaths, 38% (N = 7040) were deaths with graft function. This accounts for 42.5% of all graft loss. Patient survival with graft function was 97, 91, and 86% at 1, 5, and 10 years, respectively. The risk of DWGF decreased by 67% (RR = 0.33, P < 0.001) between 1988 and 1997. The adjusted rate of DWGF was 4.6, 0.8, 2.2, and 1.4 deaths per 1000 person-years for cardiovascular disease, stroke, infections, and malignancy, respectively. The suicide rate was 15.7 versus 9.0 deaths per 100,000 person-years in the general population (P < 0.001). In multivariate analysis, the following factors were independently and significantly predictive of DWGF: white recipient, age at transplantation, ESRD caused by hypertension or diabetes mellitus, length of pretransplant dialysis, delayed graft function, acute rejection, panel reactive antibody >30%, African American donor race, age >45 years, and donor death caused by cerebrovascular disease. Conclusions. Patients with graft function have a high longterm survival. Although DWGF is a major cause of graft loss, the risk has declined substantially since 1990. Cardiovascular disease was the predominant reported cause of DWGF. Other causes vary by post-transplant time period. Attention to atherosclerotic risk factors may be the most important challenge to further improve the longevity of patients with successful renal transplants. C1 Univ Michigan, Dept Biostat & Epidemiol, Ann Arbor, MI 48109 USA. NIDDKD, US Renal Data Syst, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. RP Ojo, AO (reprint author), Univ Michigan, Med Ctr, Dept Internal Med, 3914 Taubman Ctr,Box 0364, Ann Arbor, MI 48109 USA. NR 43 TC 438 Z9 462 U1 2 U2 5 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2000 VL 57 IS 1 BP 307 EP 313 DI 10.1046/j.1523-1755.2000.00816.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 276GN UT WOS:000084868200033 PM 10620213 ER PT J AU Kohda, Y Murakami, H Moe, OW Star, RA AF Kohda, Y Murakami, H Moe, OW Star, RA TI Analysis of segmental renal gene expression by laser capture microdissection SO KIDNEY INTERNATIONAL LA English DT Article DE tissue microdissection; renal injury; nephron; fibrosis; necrosis ID POLYMERASE CHAIN-REACTION; GROWTH-FACTOR-BETA; RAT-KIDNEY; MOLECULAR ANALYSIS; NEPHRON SEGMENTS; MESSENGER-RNA; PROTECTS; ISCHEMIA; TUBULES; FAILURE AB Background. The study of normal renal physiology has been greatly aided by microdissection techniques that have delineated the exceptional functional and cellular heterogeneity both along the nephron and between different nephron populations. These techniques are not widely used to study renal injury as microdissection is difficult because of tissue necrosis or fibrosis. We developed a procedure to detect specific gene expression in specific locations of the kidney in histologic sections. Methods. The anatomic specificity of laser capture microdissection (LCM) was employed with the sensitivity of reverse transcriptase-polymerase chain reaction (RT-PCR). Results. LCM/RT-PCR detected mRNA for podoplanin in 2% of a single glomerulus, rat basic amino acid transporter in 6% of a single cross-section of proximal straight tubule, and renin in eight proximal convoluted tubule cross-sections. LCM/RT-PCR could isolate pure populations of proximal convoluted tubules, proximal straight tubules, and thick ascending limbs from renal histologic sections, although pure collecting ducts could not be isolated. LCM/RT-PCR localized ischemia reperfusion-induced induction of KC/interleukin-8 primarily to the medullary thick ascending limb, and detected transforming growth factor-beta (TGF-beta) mRNA in glomeruli of a patient with membranous glomerulonephropathy. Conclusions. When used with an appropriate laser spot size, LCM/RT-PCR can measure gene expression in glomeruli or specific parts of the nephron and can study alterations in steady-state mRNA levels in animal models of renal disease. The applications, limitations, and refinements of this approach are discussed. C1 NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Vet Adm Med Ctr, Dallas, TX USA. RP Star, RA (reprint author), NIH, Bldg 10,Room 3N108,10 Ctr Dr MSC 1268, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK48482, DK54396, DK45923] NR 23 TC 78 Z9 81 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2000 VL 57 IS 1 BP 321 EP 331 DI 10.1046/j.1523-1755.2000.00824.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 276GN UT WOS:000084868200035 PM 10620215 ER PT J AU Kimmel, PL AF Kimmel, PL TI Just whose quality of life is it anyway? Controversies and consistencies in measurements of quality of life SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT XVth International Congress of Nephrology CY MAY 08-09, 1999 CL PUNTA DEL ESTE, URUGUAY DE hemodialysis; chronic kidney disease; depression; social support; effects of illness ID STAGE RENAL-DISEASE; BECK DEPRESSION INVENTORY; OF-LIFE; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; BEHAVIORAL COMPLIANCE; HEALTH-STATUS; FUNCTIONAL HEALTH; FAMILY SUPPORT; SOCIAL SUPPORT AB The proper means of measuring quality of life (QOL) in patients with renal disease, including end-stage renal disease, have not been agreed upon. QOL has health-related and non-health-related domains. QOL measures may be subjective or objective, function-based or satisfaction-based, non-specific or applied to a particular disease. Domains of health-related QOL typically include measures of physical functioning, mental health, and social relationships. There is increasing interest in measures of happiness or global satisfaction in patients and in assessing how patients' feelings reflect their relationships with caregivers. There are advantages and disadvantages to the use of older psychologically based measures as QOL indicators as well as newer questionnaires such as the Kidney Disease Quality of Life (KDQOL) Instrument. Challenges for the future include correlation of QOL measures with patient biochemical and disease measures, and with meaningful patient outcomes. Most important, we must create and apply methods to enhance our patients' QOL. C1 NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. RP Kimmel, PL (reprint author), NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Room 6AS19B,Bldg 45, Bethesda, MD 20892 USA. NR 63 TC 44 Z9 44 U1 1 U2 8 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2000 VL 57 SU 74 BP S113 EP S120 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 276GQ UT WOS:000084868400019 ER PT J AU Strandberg, J AF Strandberg, J TI The future of research on NHPs: Southwest Regional Primate Research Center SO LAB ANIMAL LA English DT Article AB The NIH's recent dedication of a new regional primate research center at the Southwest Foundation for Biomedical Research underscores the importance of disease research with NHPs, especially in light of the emergence of new and deadly viral diseases. C1 NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Strandberg, J (reprint author), NIH, Natl Ctr Res Resources, 6705 Rockledge Dr,Suite 6168, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JAN PY 2000 VL 29 IS 1 BP 26 EP 29 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 275VU UT WOS:000084841500007 ER PT J AU Devouassoux-Shisheboran, M Vortmeyer, AO Silver, SA Zhuang, ZP Tavassoli, FA AF Devouassoux-Shisheboran, M Vortmeyer, AO Silver, SA Zhuang, ZP Tavassoli, FA TI Teratomatous genotype detected in malignancies of a non-germ cell phenotype SO LABORATORY INVESTIGATION LA English DT Article ID OVARIAN TERATOMAS; CYSTIC TERATOMA; ANGIOSARCOMA; ORIGIN AB Originating from post-meiotic germ cells, mature ovarian teratomas (MOT) are genetically homozygous tumors within heterozygous hosts. MOT may be associated with malignant tumors of a non-germ cell phenotype (so-called malignant transformation). Based on the presence of in situ changes, some cases have been hypothesized to arise from teratomatous tissue. However, other malignancies associated with mature teratomas, such as sarcomas, may originate from either teratomatous elements or preexisting somatic ovarian tissue. Eight cases of MOT containing various histologic types of malignancy, including four squamous cell carcinomas, two sarcomas, one thyroid carcinoma, and one carcinoid tumor, were selected for study. Using selective tissue microdissection and PCR-based analysis of the extracted DNA, we compared the genotypic pattern of the mature teratomatous components to the associated malignant neoplasm with a random panel of highly informative genetic markers for different chromosomes. In all eight cases, genetic analysis of the malignant component revealed a homozygous genotype. In seven cases, the genetic profiles of mature teratomas and the associated malignant tumors were identical, suggesting a direct pathogenetic relationship between these lesions. In one case, the malignant component revealed homozygosity of different alleles compared with mature teratoma, suggesting independent teratomatous growth processes. This finding indicates that some ovarian malignancies of the non-germ cell phenotype arise in teratoma and fall into the spectrum of germ cell tumors. C1 NINDS, SNB, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA. RP Zhuang, ZP (reprint author), NINDS, SNB, NIH, Bldg 10,Room 5037,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 14 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2000 VL 80 IS 1 BP 81 EP 86 DI 10.1038/labinvest.3780011 PG 6 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 277MR UT WOS:000084937800010 PM 10653006 ER PT S AU Teng, CT Grant, DJ Negishi, M AF Teng, CT Grant, DJ Negishi, M BE Shimazaki, K Tsuda, H Tomita, M Kuwata, T Perraudin, JP TI Lactoferrin gene: methylation, expression and cancer SO LACTOFERRIN: STRUCTURE, FUNCTION AND APPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 4th International Conference on Lactoferrin Structure, Function and Applications CY MAY 18-22, 1999 CL SAPPORO, JAPAN SP Morinaga Milk Ind Co Ltd, Meiji Milk Prod Co Ltd, Agennix Inc, Armor Proteines SAS, Avonmore Waterford Ingredients, Biopole, DMV Int, Domo, Ferro Dynam Inc, Gist Brocades B V, Jasco Corp, Pharming Holding N V, San Ei Gen F F I Inc, Snow Brand Milk Prod Co Ltd, Akiyama Fdn, Tatua Co op Dairy Co Ltd, Ajinomoto Co Ltd, Aliment Ind Co Ltd, Dainippon Printing Co Ltd, Genzyme Transgen Corp Japan, Hokkaido Milk Record & Test Assoc, Kanebo Foods Co Ltd, Mitsui & Co Ltd, Nestle Japan Ltd, Nippon Beet Sugar Mfg Co Ltd, Nippon Prot Co Ltd, Nissei Kyoueki Co Ltd, NFO Co Ltd, Onishi Food Co Ltd, Sci Tanaka Co Ltd, Sigma Genosys Japan Co Ltd SRL Inc Ltd, Taiyo Yushi K K, Takanashi Milk Ind Co, Takasago Int Corp, T Hasegawa Co Ltd, Toppan Print Co Ltd, Yotsuba Milk Prod Co Ltd, Zeria Pharmaceut Co Ltd, Dept Econ Affairs, Hokkaido Govt, Minist Agr, Forestry & Fisheries Japan, Japan Soc Biosci BioTechnol & Agrochem, Japan Biochem Soc, Japan Natl Assoc Racing, Hokkaido Fujihira Ind Co Ltd DE automatic sequencing; CpG site; estrogen; methylation sensitive restriction enzyme; neonatal ID DNA METHYLATION; MESSENGER-RNA; BINDING-PROTEIN; BREAST-CANCER; PROMOTER; CELLS; MICE; DIETHYLSTILBESTROL; MYELOPOIESIS; MUTATION AB Altered DNA methylation patterns have been correlated with changes in gene expression and are a consistent molecular change in human tumors. DNA hypermethylation has been observed in the promoter region of tumor suppressor and other genes in a variety of carcinomas. Lactoferrin, a multifunctional iron-binding glycoprotein, was found decreased or absent in most cancer cells suggesting, that the control of expression in this gene may be impaired as a result of tumorgenesis. Previous work in our laboratory revealed differences in the degree of methylation with methylation-sensitive restriction enzyme sites in the lactoferrin gene in genomic DNA isolated from the leukemic cells of cancer patients, human breast cancer and leukemia cell lines. In addition, changes in lactoferrin expression were detected by immunohistochemical staining of these tissues. These data supported the link between the methylation state of the lactoferrin gene and its expression. In malignancy, overall decreases in the total amount of methylated DNA have been consistently found. However, hypermethylation of DNA, especially in the 5' areas of specific genes, has been observed in cancer. We analyzed the transcriptional activity of lactoferrin promoter in transiently transfected human endometrial carcinoma cells after in vitro methylation to explore the relationship between methylation status of the lactoferrin promoter and its expression in normal and abnormal tissues. The in vivo methylation state of three sites in the promoter region was assessed using Southern blot analysis of DNA digested with methylation-insensitive and sensitive restriction enzymes. We found correlation between the tissue-specific pattern of methylation and constitutive expression of lactoferrin. With respect to alterations in the methylation state of the lactoferrin gene promoter in abnormal tissue, we examined five CpG sites of the lactoferrin promoter from neonatal estrogen-exposed and then estrogen-treated mature mouse uterus. We found that a specific CpG site in the lactoferrin promoter was demethylated by neonatal DES treatment. The mode of demethylation is reminiscent of uterine tumor formation, which also depends on both neonatal estrogen-exposure and ovarian hormone stimulation in adulthood. Collectively the results suggest that the methylation state of the lactoferrin gene promoter affects its expression in normal and abnormal cells. Moreover, alteration of the methylation state at a specific site which resulted from earlier DES exposure could serve as a marker for tumorigenesis. C1 NIEHS, Gene Regulat Grp, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), NIEHS, Gene Regulat Grp, Lab Reprod & Dev Toxicol, NIH, POB 12233,MD E2-01, Res Triangle Pk, NC 27709 USA. EM Teng@niehs.nih.gov NR 40 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50317-X J9 INT CONGR SER JI Int. Congr. Ser. PY 2000 VL 1195 BP 247 EP 255 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ32M UT WOS:000087987900029 ER PT J AU McCubrey, JA May, WS Duronio, V Mufson, A AF McCubrey, JA May, WS Duronio, V Mufson, A TI Serine/threonine phosphorylation in cytokine signal transduction SO LEUKEMIA LA English DT Article DE signal transduction; phosphorylation; cytokine; apoptosis; chemotherapeutic drugs ID ACTIVATED-PROTEIN-KINASE; COLONY-STIMULATING FACTOR; P70 S6 KINASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; RECEPTOR TYROSINE KINASE; CELL-CYCLE REGULATION; DNA-BINDING ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSCRIPTIONAL ACTIVATION; HEMATOPOIETIC-CELLS AB Over the past decade, the involvement of tyrosine kinases in signal transduction pathways evoked by cytokines has been intensively investigated. Only relatively recently have the roles of serine/threonine kinases in cytokine-induced signal transduction and anti-apoptotic pathways been examined. Cytokine receptors without intrinsic kinase activity such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and the interferons were thought to transmit their regulatory signals primarily by the receptor-associated Jak family of tyrosine kinases. This family of tyrosine kinases activates STAT transcription factors, which subsequently transduced their signals into the nucleus to modulate gene expression. Cytokine receptors with intrinsic tyrosine kinase activity such as c-Kit were initially thought to transduce their signals independently of serine/threonine kinase cascades. Recently, both of these types of receptor signaling pathways have been shown to interact with serine/threonine kinase pathways as maximal activation of these tyrosine kinase regulated cascades involve serine/threonlne phosphorylation modulated by, for example MAP kinases. A common intermediate pathway initiating from cytokine receptors is the Ras/Raf/MEK/ERK (MAPK) cascade, which can result in the phosphorylation and activation of additional downstream kinases and transcription factors such as p90(Rsk), ORES, Elk and Egr-1. Serine/threonine phosphorylation is also involved in the regulation of the apoptosis-controlling Bcl-2 protein, as certain phosphorylation events induced by cytokines such as IL-3 are anti-apoptotic, whereas other phosphorylation events triggered by chemotherapeutic drugs such as Paclitaxel are associated with cell death. Serine/threonine phosphorylation is implicated in the etiology of certain human cancers as constitutive serine phosphorylation of STATs 1 and 3 is observed in chronic lymphocytic leukemia and can be inhibited by the chemotherapeutic drug fludarabine, Serine/threonine phosphorylation also plays a role in the etiology of immunodeficiencies. Activated STAT5 proteins are detected in reduced levels in lymphocytes recovered from HIV-infected individuals and immunocompromised mice. Serine/threonine phosphorylation may be an important target of certain chemotherapeutic drugs which recognize the activated proteins. This meeting report and mini-review will discuss the interactions of serine/threonine kinases with signal transduction and apoptotic molecules and how some of these pathways can be controlled by chemotherapeutic drugs. C1 E Carolina Univ, Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. Univ Texas, Med Branch, Sealy Ctr Oncol Hematol, Galveston, TX 77550 USA. Univ British Columbia, Dept Med, Vancouver, BC, Canada. Jack Bell Res Ctr, VH&HSC, Vancouver, BC, Canada. NCI, Canc Immunol & Hematol Branch, NIH, Bethesda, MD 20892 USA. RP McCubrey, JA (reprint author), E Carolina Univ, Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. OI McCubrey, James/0000-0001-6027-3156 FU NCI NIH HHS [R01CA51025] NR 141 TC 150 Z9 155 U1 1 U2 9 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2000 VL 14 IS 1 BP 9 EP 21 DI 10.1038/sj.leu.2401657 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 277GX UT WOS:000084925300002 PM 10637471 ER PT J AU Pospisil, R Silverman, GJ Marti, GE Aruffo, A Bowen, MA Mage, RG AF Pospisil, R Silverman, GJ Marti, GE Aruffo, A Bowen, MA Mage, RG TI CD5 is a potential selecting ligand for B-cell surface immunoglobulin: A possible role in maintenance and selective expansion of normal and malignant B cells SO LEUKEMIA & LYMPHOMA LA English DT Article DE B-CLL; B-cell superantigens; CD5 domains; surface immunoglobulin; positive selection V-H framework regions ID CHRONIC LYMPHOCYTIC-LEUKEMIA; VARIABLE REGION GENES; CYSTEINE-RICH DOMAIN; MOLECULAR CHARACTERIZATION; ANTIGENIC EXPRESSION; LYMPHOID ORGANS; T-CELL; RECEPTOR; REPERTOIRE; HEAVY AB Although the function of CD5 on B cells is unknown, previous studies suggested that CD5 interaction with V-H framework regions of surface immunoglobulins (Igs) may contribute to survival and expansion of B cells, Here we used B-chronic lymphocytic leukemia (B-CLL) cells and transformed B-cell Lines from normal and B-CLL patients to study CD5-Ig interactions. Immobilized Ig binds and permits isolation of CD5 from lysates of CD5-expressing cell lines. Immunoglobulins or Fab fragments of different V-H families varied in their effective ness as inhibitors of anti-CD5 staining of CLL cells, appendix and tonsil tissue sections. Human Ig also binds to purified recombinant CD5. We show here for the first time that the unconventional Ig-CD5 interaction maps to the extracellular CD5-D2 domain whereas conventional epitopes recognized by anti-CD5 antibodies are localized in the D1 domain of CD5. We propose that interactions of V-H framework regions with CD5 as a ligand may maintain, select or expand normal, autoimmune or transformed B cells and also contribute to skewing of the normal V-H repertoire. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,11N311 MSC 1892,10 Ctr Dr, Bethesda, MD 20892 USA. RI Pospisil, Richard/B-7467-2012 FU NIAID NIH HHS [R01 AI 40305] NR 72 TC 20 Z9 20 U1 0 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 2000 VL 36 IS 3-4 BP 353 EP + DI 10.3109/10428190009148857 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 279AG UT WOS:000085020700015 PM 10674908 ER PT B AU Zivadinovic, D Dzakula, Z Andjus, RK AF Zivadinovic, D Dzakula, Z Andjus, RK BE Heldmaier, G Klingenspor, M TI Temperature modulation of glucocorticoid-receptor affinity in a hibernator, the European ground squirrel, and a non-hibernator, the rat SO LIFE IN THE COLD LA English DT Proceedings Paper CT 11th International Hibernation Symposium on Life in the Cold CY AUG 13-18, 2000 CL JUNGHOLZ, AUSTRIA ID LACTATE-DEHYDROGENASE; FUNCTIONAL-PROPERTIES; FISH AB The time course of the specific binding of triamcinolone acetonide (a synthetic glucocorticoid) to its cytoplasmic receptor (rat and ground squirrel liver cytosol preparations) has been recorded at a series of incubation temperatures, from 0 to 37 degreesC. Experimental results were fitted with a theoretical model accounting for the temperature dependence of complex formation and dissociation. A pronounced instability of the hormone-receptor complex was noted at relatively high incubation temperatures. Binding maxims formed bell-shaped temperature dependence profiles, peaking at a considerably lower temperature in the hibernator. A detailed study of the temperature dependence of the equilibrium dissociation constant (K-D) showed that, with both preparations. K-D values substantially increased with increasing temperature above 15 degreesC ("positive temperature modulation of affinity"). A U-shaped temperature profile of the dissociation constant (K-D), with its minimum at about 10 degreesC, was obtained with preparations from the hibernator. Empirical data agreed completely with theoretical predictions, suggesting that the observed thermal modulation of affinity might be a direct consequence of intrinsic kinetic properties of steroid-receptor interactions. In the case of the rat, however, empirical data points deviated appreciably from model-predictions in the low temperature region, forming a "J"-type plot rather than the predicted U-shape profile. The lowest K-D value was situated at about 15 degreesC, five degrees above the hibernator's K, inversion temperature. In the case of both species, temperatures characterized by the smallest K, values (greatest hormone-receptor affinity) were close to body temperatures representing. temperature limits of spontaneous recovery from induced hypothermia. C1 NICHD, ERRB, NIH, Bethesda, MD 20892 USA. Mol Simulat Inc, San Diego, CA 92121 USA. Univ Belgrade, Ctr Multidisciplinary Studies, YU-11000 Belgrade, Yugoslavia. RP Zivadinovic, D (reprint author), NICHD, ERRB, NIH, Convent Dr,MSC 4510, Bethesda, MD 20892 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-67410-1 PY 2000 BP 277 EP 284 PG 8 WC Physiology; Zoology SC Physiology; Zoology GA BR21M UT WOS:000165863300030 ER PT B AU Marjanovic, M Dzakula, Z Zivadinovic, D Andjus, RK AF Marjanovic, M Dzakula, Z Zivadinovic, D Andjus, RK BE Heldmaier, G Klingenspor, M TI Temperature dependence of coupled and uncoupled oxidations in brain synaptosomes from hibernators and non-hibernators SO LIFE IN THE COLD LA English DT Proceedings Paper CT 11th International Hibernation Symposium on Life in the Cold CY AUG 13-18, 2000 CL JUNGHOLZ, AUSTRIA AB In the presence of saturating glucose concentrations, Arrhenius plot for glucose oxidation in the ground squirrel synaptosomes showed no discontinuity, while a sharp break was present when rat synaptosomes were used. The addition of 2,4-dinitrophenol (DNP), a potent uncoupler of oxidative phosphorylation, resulted in an increase of glucose oxidation rates. The stimulatory effect was significantly higher in the case of hibernator's synaptosomes, and a break occurred in the Arrhenius plot for both species. Multiple-dose experiments with DNP provided bell-shaped dose-response profiles, quantitatively defined by an optimal stimulatory dose (EDopt) and the corresponding maximum stimulatory effect (S-max). Cooling from 32 degrees to 5 degreesC resulted in the decrease of both EDopt and S-max (shifting to the left and flattening of the dose-response profiles). The effect of temperature was enhanced by factors capable of further reducing the rate of ATP generation (low substrate concentration), and opposed by factors leading to reduced rates of ATP utilization (suppression of active transport by the elimination of sodium ions in the medium). In comparison to rat darn, ground squirrel synaptosomes showed a markedly increased responsiveness to DNP stimulation (much higher S-max), and an increased resistance to cold-induced alterations of the dose-response profiles. In addition, the use of DNP and low incubation temperature (5 degreesC) revealed differences between active and actually hibernating hibernator, in correlation with data on their respective tolerances to reduced body temperature. C1 Eastern Illinois Univ, Dept Sci Biol, Charleston, IL 61920 USA. Mol Simulat Inc, San Diego, CA 92121 USA. NICHD, ERRB, NIH, Bethesda, MD 20892 USA. Univ Belgrade, Ctr Multidisciplinary Studies, YU-11000 Belgrade, Yugoslavia. RP Marjanovic, M (reprint author), Eastern Illinois Univ, Dept Sci Biol, Charleston, IL 61920 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 3-540-67410-1 PY 2000 BP 361 EP 368 PG 8 WC Physiology; Zoology SC Physiology; Zoology GA BR21M UT WOS:000165863300039 ER PT J AU Schneeweiss, FHA Mukherjee, AS Sharan, RN Feinendegen, LE Muller-Gartner, HW AF Schneeweiss, FHA Mukherjee, AS Sharan, RN Feinendegen, LE Muller-Gartner, HW TI Response of high mobility group proteins of human kidney T1 and murine L 929 cell lines to heat shock SO LIFE SCIENCES LA English DT Article DE T1 cells in vitro; L 929 cells in vitro; high mobility group proteins; heat shock; chromatin organization; DNase I ID DROSOPHILA AB High mobility group (HMG) proteins in human kidney T1 and murine L 929 cells have been investigated after exposure to heat shock at 41 degrees C and their influence on the organizational change of chromatin under heat shock condition has been examined. Results reveal that the two cell lines show differential response of the HMG proteins 1 & 2 and 14 & 17 to heat shock. Neither T1 nor L 929 cells show significant differences in response to heat shock with respect to the binding affinities of HMG proteins 1 & 2 or 14 & 17 to DNA, as revealed by DNase I sensitivity and chromatin reconstitution assays. Furthermore, the HMG proteins of both the non-heat shocked and the heat shocked T1 and L 929 cells can recover their chromatin activity following reconstitution. These findings suggest that although the HMG proteins might undergo some change in response to heat shock, their inherent potential of reassociation with DNA is still retained. C1 Res Ctr, Inst Med, D-52425 Julich, Germany. Univ Calcutta, Dept Zool, Genet Res Unit, Calcutta 700019, W Bengal, India. NE Hill Univ, Dept Biochem, Shillong 793022, Meghalaya, India. NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA. Univ Dusseldorf, Dept Nucl Med, D-40001 Dusseldorf, Germany. RP Schneeweiss, FHA (reprint author), Res Ctr, Inst Med, D-52425 Julich, Germany. RI Sharan, Rajeshwar/L-3007-2016 OI Sharan, Rajeshwar/0000-0002-7120-8023 NR 15 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PY 2000 VL 66 IS 3 BP 193 EP 200 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 268FF UT WOS:000084403100002 PM 10665993 ER PT J AU Zia, H Leyton, J Casibang, M Hau, V Brenneman, D Fridkin, M Gozes, I Moody, TW AF Zia, H Leyton, J Casibang, M Hau, V Brenneman, D Fridkin, M Gozes, I Moody, TW TI (N-stearyl, norleucine(17)) VIP hybrid inhibits the growth of pancreatic cancer cell lines SO LIFE SCIENCES LA English DT Article DE VIP antagonist; pancreatic cancer; cAMP; c-fos ID VASOACTIVE-INTESTINAL-PEPTIDE; ADENYLATE-CYCLASE; LUNG-CANCER; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; RECEPTOR; POLYPEPTIDE; ADENOCARCINOMA; BOMBESIN; CARCINOMA AB The effects vasoactive intestinal peptide (VIP) antagonists were investigated on pancreatic cancer cell lines. (N-Stearyl, Norleucine(17)) VIP hybrid ((SN)VIPhyb) inhibited I-125-VIP binding to human Capan-2 cells with an IC50 value of 0.01 mu M whereas VIPhybrid had an IC50 value of 0.2 mu M. By RT-PCR and Northern blot, VPAC(1) receptor mRNA was detected in CAPAN-2 cells. One mu M (SN)VIPhyb and 10 mu M VIPhyb inhibited the ability of 30 nM VIP to elevate cyclic AMP and increase c-fos mRNA. (SN)VIPhyb, 1 mu M inhibited the clonal growth of CAPAN-2 cells in vitro. In vivo, (SN)VIPhyb (10 mu g/day s.c.) inhibited CAPAN-2 xenograft growth in nude mice. These results indicate that (SN)VIPhyb is a pancreatic cancer VPAC receptor antagonist. C1 NCI, Med Branch, Cell & Canc Biol Dept, Rockville, MD 20850 USA. NICHHD, Unit Neurochem, Dev Neurobiol Lab, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Moody, TW (reprint author), NCI, Med Branch, Cell & Canc Biol Dept, Rockville, MD 20850 USA. NR 31 TC 18 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PY 2000 VL 66 IS 5 BP 379 EP 387 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 268FL UT WOS:000084403600002 PM 10670826 ER PT J AU Peters, DC Korosec, FR Grist, TM Block, WF Holden, JE Vigen, KK Mistretta, CA AF Peters, DC Korosec, FR Grist, TM Block, WF Holden, JE Vigen, KK Mistretta, CA TI Undersampled projection reconstruction applied to MR angiography SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE rapid imaging; projection reconstruction; contrast-enhanced; sparse sampling ID FIELD-OF-VIEW; ACQUISITION ORDER; K-SPACE; REDUCTION AB Undersampled projection reconstruction (PR) is investigated as an alternative method for MRA (MR angiography). In conventional 3D Fourier transform (FT) MRA, resolution in the phase-encoding direction is proportional to acquisition time. Since the PR resolution in all directions is determined by the readout resolution, independent of the number of projections (N-p), high resolution can be generated rapidly. However, artifacts increase for reduced N-p. In X-ray CT, undersampling artifacts from bright objects like bone can dominate other tissue. In MRA, where bright, contrast-filled vessels dominate, artifacts are often acceptable and the greater resolution per unit time provided by undersampled PR can be realized. The resolution increase is limited by SNR reduction associated with reduced voxel size. The hybrid 3D sequence acquires fractional echo projections in the k(x)-k(y) plane and phase encodings in k(z). PR resolution and artifact characteristics are demonstrated in a phantom and in contrast-enhanced volunteer studies. Magn Reson Med 43:91-101,2000, (C) 2000 Wiley-Liss, Inc. C1 Univ Wisconsin, Dept Phys, Madison, WI 53706 USA. Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA. RP Peters, DC (reprint author), NIH, Bldg 10,BID 416,10 Ctr Dr,MSC 1061, Bethesda, MD 20892 USA. FU NCI NIH HHS [T32 CA09206]; NHLBI NIH HHS [R01 HL52747] NR 31 TC 238 Z9 238 U1 1 U2 9 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JAN PY 2000 VL 43 IS 1 BP 91 EP 101 DI 10.1002/(SICI)1522-2594(200001)43:1<91::AID-MRM11>3.0.CO;2-4 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 270MA UT WOS:000084538500011 PM 10642735 ER PT B AU Gao, XJ Lester, S Veale, A Boettcher, B Currie, B McCluskey, J Chelvanayagam, G AF Gao, XJ Lester, S Veale, A Boettcher, B Currie, B McCluskey, J Chelvanayagam, G BE Kasahara, M TI HLA class I alleles in Australian aborigines and their peptide binding profiles SO MAJOR HISTOCOMPATIBILITY COMPLEX: EVOLUTION, STRUCTURE AND FUNCTION LA English DT Proceedings Paper CT 6th International Workshop on Major Histocompatibility Complex Evolution CY MAY 25-29, 1999 CL HAYAMA, JAPAN SP Minist Educ, Sci, Sports & Culture Japan, Grad Univ, Adv Studies DE major histocompatibility complex; class I human leucocyte antigen gene; human evolution; peptide presentation; Australian aborigines ID MAJOR HISTOCOMPATIBILITY COMPLEX; ANCHOR RESIDUES; B ALLELES; MOLECULES; EVOLUTION; DIVERSITY; SELECTION; HLA-DRB1; LOCI AB The HLA system is under balancing selection. HLA alleles are maintained in populations by their divergent functions. The peptide binding profiles of HLA alleles may hold the key to a better understanding of HLA diversification and polymorphism maintenance. Long isolated Australian aboriginal populations provide a good model for these studies. The four HLA-A, seven B and five or six C alleles commonly detected in them represent the minimum class I repertoire carried by the founder group as well as the minimum class I polymorphism that needs to be maintained in these populations. All these alleles have a unique combination of the P2 and P9 anchor preferences indicating unique peptide binding profiles that have 'earned' their place in the minimum allele set. This study of Australian aborigines provides further insights into the mechanism of HLA evolution in general. C1 NCI, FCRD, SAIC Frederick, IRSP, Frederick, MD 21701 USA. RP Gao, XJ (reprint author), NCI, FCRD, SAIC Frederick, IRSP, Frederick, MD 21701 USA. RI McCluskey, James/A-1291-2007 OI McCluskey, James/0000-0002-8597-815X NR 31 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-70276-8 PY 2000 BP 446 EP 462 PG 17 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA BP68Z UT WOS:000085866100033 ER PT J AU Chadwick, BP Leyne, M Gill, S Liebert, CB Mull, J Mezey, E Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Gusella, JF Slaugenhaupt, SA AF Chadwick, BP Leyne, M Gill, S Liebert, CB Mull, J Mezey, E Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Gusella, JF Slaugenhaupt, SA TI Cloning, mapping, and expression of a novel brain-specific transcript in the Familial Dysautonomia candidate region on Chromosome 9q31 SO MAMMALIAN GENOME LA English DT Article ID EXON AMPLIFICATION; GENES; PROTEINS C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. NIMH, Genet Lab, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Unit Dev Mol Biol & Genet Engn, IL-91120 Jerusalem, Israel. NYU, Dept Pediat, Sch Med, New York, NY 10016 USA. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. RP Slaugenhaupt, SA (reprint author), HIM Bldg,Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Brownstein, Michael/B-8609-2009; Pinkett, Heather/M-9235-2014 FU NINDS NIH HHS [NS36326] NR 15 TC 6 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JAN PY 2000 VL 11 IS 1 BP 81 EP 83 DI 10.1007/s003350010017 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 267EU UT WOS:000084344800017 PM 10603000 ER PT J AU Coelho, VR Cooper, RA Rodrigues, SD AF Coelho, VR Cooper, RA Rodrigues, SD TI Burrow morphology and behavior of the mud shrimp Upogebia omissa (Decapoda : Thalassinidea : Upogebiidae) SO MARINE ECOLOGY PROGRESS SERIES LA English DT Article DE shrimp; burrow; feeding; Upogebia; decapoda; thalassinidea ID CALLIANASSA-CALIFORNIENSIS; FUNCTIONAL-MORPHOLOGY; BRITISH-COLUMBIA; TROPHIC MODES; CRUSTACEA; BIOTURBATION; ECOLOGY; BRAZIL; COMMUNITIES; MEIOFAUNA AB The burrow morphology, burrowing behavior and feeding mechanisms of the thalassinidean shrimp Upogebia omissa were studied. Twenty burrow casts were made in situ with epoxy resin, and an overall 'Y' shape was most frequently observed. Several burrows consisted of a single, oblique tunnel; burrow diameter was positively correlated with burrow length, maximum depth and distance between openings. Additionally, burrow length was positively associated with maximum depth, indicating that as burrow length increased burrow depth increased; i.e, burrows spread vertically rather than horizontally, Total sediment displacement by the burrows accounted for 2.6 % of sediment to a depth of 30 cm. The sediment-water interface increased by 290 % in areas containing burrows compared to areas without burrows. Solitary adults were trapped in 15 casts. Three casts were interconnected, but each burrow contained only 1 shrimp. Regression analysis revealed shrimp length to be positively correlated with burrow diameter and area. In aquaria, U. omissa displayed a dual feeding behavior: the shrimp filtered suspended particles, and also fed directly on the sediment. Filter-feeding occurred mainly within U-shaped tunnels, while deposit-feeding was observed in association with the oblique tunnels of the burrow. Although filter-feeding has been considered as the main trophic mode in upogebiids, we present evidence that U. omissa may have a more pronounced deposit-feeding behavior than described for other species of this group. Based on our findings, we suggest that current models on the functional morphology of burrows in relation to feeding should be used cautiously in inferring the trophic behavior of these shrimp. C1 Univ Sao Paulo, Inst Biociencias, Dept Zool, BR-05422970 Sao Paulo, Brazil. NIH, Bethesda, MD 20892 USA. Univ Sao Paulo, Inst Biociencias, Dept Ecol Geral, BR-05422970 Sao Paulo, Brazil. RP Coelho, VR (reprint author), Columbia Univ, Biosphere Ctr 2, 32540 Biosphere Rd, Oracle, AZ 85623 USA. EM vcoelho@bio2.edu NR 49 TC 46 Z9 47 U1 0 U2 8 PU INTER-RESEARCH PI OLDENDORF LUHE PA NORDBUNTE 23, D-21385 OLDENDORF LUHE, GERMANY SN 0171-8630 J9 MAR ECOL PROG SER JI Mar. Ecol.-Prog. Ser. PY 2000 VL 200 BP 229 EP 240 DI 10.3354/meps200229 PG 12 WC Ecology; Marine & Freshwater Biology; Oceanography SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Oceanography GA 342NM UT WOS:000088651400020 ER PT J AU Lamb, ME AF Lamb, ME TI The history of research on father involvement: An overview SO MARRIAGE AND FAMILY REVIEW LA English DT Article; Proceedings Paper CT Conference on Father Involvement CY OCT 10-11, 1996 CL BETHESDA, MARYLAND SP NICHHD, Family & Child Well Being Network DE father involvement; fatherhood; history AB Both our understanding and operationalization of fatherhood and father involvement have changed over time. Fatherhood has always been a multifaceted concept, although over time the dominant or defining motif has shifted in turn from moral guidance to breadwinning to sex-role modeling, marital support, and finally nurturance. As a result of these changing concepts, the extent of father involvement has been viewed and indexed in different ways at different times. In the late 1960s and early 1970s, at a time when societal concerns about the effects of fatherlessness were coming to the fore, social scientists also became much more interested in quantification of concepts such as father involvement, motivated in part by the emergence and popularity of time-use methodologies. This prompted a shift from a focus on qualitative dimensions (such as masculinity and dominance) to quantifiable dimensions (the amount of time spent by fathers with their children). This led to a restricted focus on paternal nurturance with little if any attention paid to the other functions or aspects of fatherhood. The narrowly focused view of fatherhood that resulted, ignored subcultural variation in the definition and understanding of fatherhood. Social scientists are only now beginning to seek a broader and more inclusive understanding of fatherhood-efforts that should permit more insightful research on the effects of variations in performance of the relevant roles. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20814 USA. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, 9190 Rockville Pike, Bethesda, MD 20814 USA. NR 45 TC 158 Z9 163 U1 10 U2 60 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0149-4929 J9 MARRIAGE FAM REV JI Marriage Fam. Rev. PY 2000 VL 29 IS 2-3 BP 23 EP 42 PG 20 WC Family Studies SC Family Studies GA 324GG UT WOS:000087613000003 ER PT J AU Marsiglio, W Day, RD Lamb, ME AF Marsiglio, W Day, RD Lamb, ME TI Exploring fatherhood diversity: Implications for conceptualizing father involvement SO MARRIAGE AND FAMILY REVIEW LA English DT Article; Proceedings Paper CT Workshop on the Theory Construction and Research Methodology CY 1997 CL WASHINGTON, D.C. SP Natl Council Family Relat DE fatherhood; father involvement ID FAMILY TRANSCENDENCE; PARADIGM; CHILDREN; DIFFERENTIATION AB Our analysis, grounded in a social constructionist perspective, explores the theoretical and political complexities facing researchers and policymakers as they attempt to conceptualize, study, and promote fathers' involvement with their children. Taking into account the growing diversity of life course and residency patterns for men and children today, we stress how the definition of fatherhood and conceptualization of paternal involvement are interwoven. As our starting point, we highlight how diverse stakeholders construct differing images and types of fatherhood during an era when men are "doing fatherhood" in a wide range of contexts. Next, we explore issues associated with a broad conceptualization of father involvement, influence, and motivation with an eye toward fatherhood diversity. We then consider how several family processes are implicated in the way men develop, negotiate, and sustain their rights, privileges, and obligations as fathers in different types of family structures. We conclude by suggesting how our treatment of these issues can guide future research an fatherhood. C1 Univ Florida, Gainesville, FL 32611 USA. Brigham Young Univ, Provo, UT 84602 USA. Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. RP Marsiglio, W (reprint author), Univ Florida, Gainesville, FL 32611 USA. NR 78 TC 55 Z9 56 U1 6 U2 24 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0149-4929 J9 MARRIAGE FAM REV JI Marriage Fam. Rev. PY 2000 VL 29 IS 4 BP 269 EP 293 DI 10.1300/J002v29n04_03 PG 25 WC Family Studies SC Family Studies GA 327NG UT WOS:000087799500003 ER PT J AU Cabrera, N Peters, HE AF Cabrera, N Peters, HE TI Public policies and father involvement SO MARRIAGE AND FAMILY REVIEW LA English DT Article DE fatherhood; family policy ID CHILD-SUPPORT; SCHEDULES; OUTCOMES; CUSTODY; IMPACT; WORK AB The last two decades have been marked by a series of social and policy developments that are changing both how men see themselves as fathers and how policies conceptualize and encourage their involvement in the lives of children and families. This paper focuses on several areas of intersection between research on fathers and policy. The paper first summarizes the research that led to the current political and social interest in fathers. The paper then describes the Fatherhood Initiative, a set of activities that stemmed from a 1995 memorandum from President Clinton. This Initiative led to coordinated efforts by U.S. Federal Statistical agencies to collect better data about fathers. The paper concludes with a discussion of what we know about the effects on father involvement of policies such as welfare reform, child support, work place policies, responsible fatherhood programs, and other fatherhood interventions. Examples of new programs and initiatives on father involvement are also given. C1 NICHHD, Demog & Behav Res Branch, Bethesda, MD 20892 USA. Cornell Univ, Dept Policy Anal & Management, Ithaca, NY 14853 USA. RP Cabrera, N (reprint author), NICHHD, Demog & Behav Res Branch, Bethesda, MD 20892 USA. NR 62 TC 17 Z9 18 U1 3 U2 12 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0149-4929 J9 MARRIAGE FAM REV JI Marriage Fam. Rev. PY 2000 VL 29 IS 4 BP 295 EP 314 DI 10.1300/J002v29n04_04 PG 20 WC Family Studies SC Family Studies GA 327NG UT WOS:000087799500004 ER PT J AU Smith, MV Portier, CJ AF Smith, MV Portier, CJ TI Incorporating observability thresholds of tumors into the two-stage carcinogenesis model SO MATHEMATICAL BIOSCIENCES LA English DT Article DE rodent tumor analysis; non-homogeneous coefficients; backward Kolmogorov equation ID 2-MUTATION MODEL; CANCER AB This paper discusses a general way of incorporating the growth kinetics of malignant tumors with the two-stage carcinogenesis model. The model is presented using time-homogeneous rate parameters. In that case, the differential equations comprising the model are straightforward to solve using standard numerical techniques and software, An extension of the method to time-dependent rate parameters is included in Appendix A. Allowing the rate parameters to be time-dependent does incur computational cost. An expression is given for the expected time without visible tumor, a generalization of the expected time to an observable tumor that includes the possibility of tumor regression. The model is illustrated using incidental liver tumor data in control rats from NTP rodent carcinogenicity studies, using linear birth-death kinetics of tumors combined with a non-absorbing detection limit, The approach is also shown to be potentially useful with tumor observability thresholds having more complicated features. (C) 2000 Published by Elsevier Science Inc. All rights reserved. C1 Analyt Sci Inc, Durham, NC 27713 USA. NIEHS, Lab Computat Biol & Risk Assessment, Res Triangle Pk, NC 27709 USA. RP Smith, MV (reprint author), Analyt Sci Inc, Suite 200,2605 Meridian Pkwy, Durham, NC 27713 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 19 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD JAN PY 2000 VL 163 IS 1 BP 75 EP 89 DI 10.1016/S0025-5564(99)00048-6 PG 15 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 275BT UT WOS:000084800100004 PM 10652846 ER PT J AU Klein, HG AF Klein, HG TI Transfusion safety: Avoiding unnecessary bloodshed SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID AUTOLOGOUS BLOOD; COST-EFFECTIVENESS; DONATION; RISK C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C711,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 5 Z9 6 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2000 VL 75 IS 1 BP 5 EP 7 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 270ZN UT WOS:000084567200001 PM 10630750 ER PT S AU Damjanovski, S Amano, T Li, Q Ueda, S Shi, YB Ishizuya-Oka, A AF Damjanovski, S Amano, T Li, Q Ueda, S Shi, YB Ishizuya-Oka, A BE Zakeri, Z Lockshin, RA MartinezA, C TI Role of ECM remodeling in thyroid hormone-dependent apoptosis during anuran metamorphosis SO MECHANISMS OF CELL DEATH II SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd Annual Conference of the International-Cell-Death-Society CY MAY 06-10, 2000 CL ESCORIAL, SPAIN SP Int Cell Death Soc, European Commiss, NIH, CUNY, Queens Coll, BD Biosci, Biocolor, Biomol, Intergen, Merck, Nature, Pharmacia, R&D Syst, St Johns Univ DE thyroid hormone; amphibian metamorphosis; matrix metalloproteinases; apoptosis ID PROGRAMMED CELL-DEATH; IMPLICATES DISTINCT FUNCTIONS; SMALL-INTESTINE; TRANSCRIPTIONAL ACTIVATION; RECEPTOR SUPERFAMILY; EXTRACELLULAR-MATRIX; MOLECULAR MECHANISMS; HUMAN STROMELYSIN-3; FROG METAMORPHOSIS; XENOPUS-LAEVIS AB Programmed cell death or apoptosis is an important aspect in organogenesis and tissue remodeling. It is precisely controlled both temporally and spatially during development. Amphibian metamorphosis is an excellent model to study developmental control of apoptosis in vertebrates. This process involves the transformation of essentially every organ/tissue as tadpoles change to frogs, yet is controlled by a single hormone, thyroid hormone (TH). Although different organs and tissues undergo vastly different developmental changes, including de novo development and total resorption, most require apoptotic elimination of at least some cell types. Such properties and the dependence on TH make frog metamorphosis a unique model to isolate and functionally characterize genes participating in the regulation of tissue specific cell death during organ development in vertebrates. Indeed, molecular studies of the TH-dependent gene regulation cascade have led to the discovery of a group of genes encoding matrix metalloproteinases (MMPs) participating in metamorphosis. In vivo and in vitro studies have provided strong evidence to support a role of MMP-mediated remodeling of the extracellular matrix in regulating apoptotic tissue remodeling during metamorphosis. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Dokkyo Univ, Sch Med, Dept Histol & Neurobiol, Mibu, Tochigi 32102, Japan. RP Shi, YB (reprint author), NICHHD, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 53 TC 12 Z9 13 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-320-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 926 BP 180 EP 191 PG 12 WC Cell Biology; Multidisciplinary Sciences SC Cell Biology; Science & Technology - Other Topics GA BT10R UT WOS:000171967000018 PM 11193034 ER PT J AU Duckers, HJ Nabel, EG AF Duckers, HJ Nabel, EG TI Prospects for genetic therapy of cardiovascular disease SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID MUSCLE CELL-PROLIFERATION; ADENOASSOCIATED VIRUS VECTORS; FIBROBLAST GROWTH-FACTOR; REPLICATION-DEFECTIVE ADENOVIRUS; DEPENDENT KINASE INHIBITOR; IN-VIVO; RECOMBINANT ADENOVIRUS; LOCAL OVEREXPRESSION; BALLOON ANGIOPLASTY; NEOINTIMA FORMATION AB An understanding of the molecular and genetic pathogenesis of cardiovascular disease might lead to the implementation of gene therapies, in the last 10 years, the field of gene therapy has matured from basic science studies to testing in animal models and to initiation of human studies. This article discusses the general principles of gene transfer and presents data from animal models and clinical trials to support its use in cardiovascular disease. C1 NHLBI, Clin Res Program, NIH, Bethesda, MD 20892 USA. Erasmus Univ, Ctr Thorax, Dept Expt Cardiol, NL-3000 DR Rotterdam, Netherlands. RP Nabel, EG (reprint author), NHLBI, Clin Res Program, NIH, Bldg 10,Room 8C103, Bethesda, MD 20892 USA. NR 53 TC 10 Z9 10 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JAN PY 2000 VL 84 IS 1 BP 199 EP + DI 10.1016/S0025-7125(05)70214-5 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 281AT UT WOS:000085136500012 PM 10685135 ER PT S AU Yoo, TS Ackerman, MJ Vannier, M AF Yoo, TS Ackerman, MJ Vannier, M BE Delp, S DiGioia, AM Jaramaz, B TI Toward a common validation methodology for segmentation and registration algorithms SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2000 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 3rd International Conference on Medical Image Computing and Computer-Assisted Intervention CY OCT 11-14, 2000 CL PITTSBURGH, PENNSYLVANIA AB The National Library of Medicine and its partners are sponsoring Insight, a public software toolkit for segmentation and registration of high dimensional medical data. An essential element of this initiative is the development of a validation methodology, a common means of comparing the precision, accuracy, and efficiency of segmentation and registration methods. The goal is to make accessible the data, protocol standards, and support soft-ware necessary for a common platform for the whole medical image processing community. This paper outlines the issues and design principles for the test and training data and the supporting software that comprise the proposed Insight Validation Suite, We present the methods for establishing the functional design requirements. We also present a framework for the validation of segmentation and registration software and make some suggestions for validation trials. We conclude with some specific recommendations to improve the infrastructure for validating medical image processing research. C1 Natl Lib Med, NIH, Bethesda, MD 20894 USA. Univ Iowa, Coll Med, Dept Radiol, Iowa City, IA 52242 USA. RP Yoo, TS (reprint author), Natl Lib Med, NIH, Bethesda, MD 20894 USA. NR 7 TC 8 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-41189-5 J9 LECT NOTES COMPUT SC PY 2000 VL 1935 BP 422 EP 431 PG 10 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BT09M UT WOS:000171938700043 ER PT S AU Mullick, R Bryan, N Butman, J AF Mullick, R Bryan, N Butman, J BE Mun, SK TI Confocal volume rendering: Fast segmentation-free visualization of internal structures SO MEDICAL IMAGING 2000: IMAGE DISPLAY AND VISUALIZATION SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE volume rendering; segmentation; visualization; diagnostic evaluation; screening; surgery pre-planning ID BRAIN IMAGES; MRI DATA; SURFACE AB Volume rendering is now a common tool for multi-dimensional data exploration in biology, medicine, meteorology, geology, material science, and other fields. In order to perform volume rendering, users are often forced to preprocess and segment their data. This step of processing before visualization often inhibits the use of volume rendering as it can be quite cumbersome and can also introduce undesirable artifacts. In order to enhance the use of direct volume visualization, powerful, yet easy-to-use methods need to be developed. In this paper, we present an approach that offers the user data-dependent control over the focal region (in physical depth terms) of the visualization. This approach enables the user to easily visualize interior structures in the dataset by controlling physically defined parameters, without performing segmentation. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM rmulick@nih.gov OI Butman, John/0000-0002-1547-9195 NR 24 TC 2 Z9 2 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3593-7 J9 PROC SPIE PY 2000 VL 3976 BP 70 EP 76 DI 10.1117/12.383084 PG 7 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28B UT WOS:000087784900008 ER PT S AU Clarke, LP Croft, BY Staab, E AF Clarke, LP Croft, BY Staab, E BE Mun, SK TI New NCI initiatives in computer aided diagnosis SO MEDICAL IMAGING 2000: IMAGE DISPLAY AND VISUALIZATION SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol AB The National Cancer Institute (NCI) is interested in supporting the development of an image database for lung cancer screening using spiral X-ray CT. A cooperative agreement is envisioned (NCI UOI support mechanism) that will involve applications from investigators who are interested in joining a consortium of institutions to construct such a database as a public resource. The intent is to develop standards for generating the database resource and to allow this database to be used for evaluating computer aided diagnostic (CAD) software methods. Initial interest is focused on spiral CT of the lung because of the recent interest in using this imaging modality for lung cancer screening for patients at high risk, where early intervention may significantly reduce cancer mortality rates. The use of CAD methods is rapidly emerging for this large-scale cancer screening application as these methods have the potential of improving the efficiency of screening. Lung imaging is a good physical model in that it involves the use of 3D CAD methods that require critical software optimization for both detection and classification (benign verses malignant cancer). In addition, the detection of change in the CT images over time, or changes in lung nodule size, has the potential to provide either improved early cancer detection or improved classification. C1 NCI, Biomed Imaging Program, Bethesda, MD 20892 USA. RP NCI, Biomed Imaging Program, Bethesda, MD 20892 USA. RI Croft, Barbara/D-1248-2013 OI Croft, Barbara/0000-0003-2544-150X NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3593-7 J9 PROC SPIE PY 2000 VL 3976 BP 370 EP 373 DI 10.1117/12.383061 PG 4 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28B UT WOS:000087784900038 ER PT S AU Long, LR Thoma, GR AF Long, LR Thoma, GR BE Hanson, KM TI Segmentation and image navigation in digitized spine x-rays SO MEDICAL IMAGING 2000: IMAGE PROCESSING, PTS 1 AND 2 SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE x-ray; image processing; Active Shape Modeling; statistical shape analysis; segmentation; NHANES; NLM AB The National Library of Medicine has archived a collection of 17,000 digitized x-rays of the cervical and lumbar spines. Extensive health information has been collected on the subjects of these x-rays, but no information has been derived from the image contents themselves. We are researching algorithms to segment anatomy in these images and to derive from the segmented data measurements useful for indexing this image set for characteristics important to researchers in rheumatology, bone morphometry, and related areas. Active Shape Modeling is currently being investigated for use in location and boundary definition for the vertebrae in these images. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Long, LR (reprint author), Natl Lib Med, Bethesda, MD 20894 USA. EM long@nlm.nih.gov NR 10 TC 6 Z9 6 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3596-1 J9 PROC SPIE PY 2000 VL 3979 BP 169 EP 179 DI 10.1117/12.387654 PG 5 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ42Z UT WOS:000088355500020 ER PT S AU Summers, RM Sneller, MC Langford, CA Shelhamer, JH Wood, BJ AF Summers, RM Sneller, MC Langford, CA Shelhamer, JH Wood, BJ BE Chen, CT Clough, AV TI Improved virtual bronchoscopy using a multi-slice helical CT scanner SO MEDICAL IMAGING 2000: PHYSIOLOGY AND FUNCTION FORM MULTIDIMENSIONAL IMAGES SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE bronchus; trachea; Wegener's granulomatosis; region growing; surface rendering; virtual bronchoscopy; visualization; multi-slice helical CT; segmentation ID ENDOBRONCHIAL LESIONS; RECONSTRUCTION; SIMULATIONS; PARAMETERS; RESOLUTION; STENOSES; DISPLAY AB Virtual bronchoscopy reconstructions of the airway noninvasively provide useful morphologic information of structural abnormalities such as stenoses and masses. To date, virtual bronchoscopy has been mainly applied to the central ah-ways. In this paper, we show how virtual bronchoscopy can be applied to more peripheral airways by making use of the capabilities of a multi-slice helical CT scanner. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM rms@nih.gov NR 22 TC 5 Z9 5 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3595-3 J9 PROC SPIE PY 2000 VL 3978 BP 117 EP 121 DI 10.1117/12.383390 PG 5 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28E UT WOS:000087787100012 ER PT S AU Yim, PJ Mullick, R Summers, RM Marcos, H Cebral, JR Lohner, R Choyke, PL AF Yim, PJ Mullick, R Summers, RM Marcos, H Cebral, JR Lohner, R Choyke, PL BE Chen, CT Clough, AV TI Measurement of stenosis from magnetic resonance angiography using vessel skeletons SO MEDICAL IMAGING 2000: PHYSIOLOGY AND FUNCTION FORM MULTIDIMENSIONAL IMAGES SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE atherosclerosis; carotid artery; stenosis; magnetic resonance angiography; surface reconstruction; deformable model; surface merging; skeletonization ID SURFACE RECONSTRUCTION; MR-ANGIOGRAPHY; IMAGES; SEGMENTATION; ANEURYSMS AB Measurement of stenosis due to atherosclerosis is essential for interventional planning. Currently, measurement of stenosis from magnetic resonance angiography (MRA) is made based on 2D maximum intensity projection (MIP) images. This methodology, however, is subjective and does not take full advantage of the 3D nature of MRA. To address these limitations we present a deformable model for reconstructing the vessel surface with particular application to the carotid artery. The deformable model is based on a cylindrical coordinate system of a curvilinear axes. In this coordinate system, the location of each point on the surface of the deformable model is described by its axial, circumferential and radial position. The points on the surface deform in the radial direction so as to minimize discontinuity in radial position between adjacent points while maximizing the proximity of the surface to local edges in the image. The algorithm has no bias towards either narrower or wider cross-sectional shapes and is thus appropriate for the measurement of stenosis. Axes of the vessels are indicated manually or determined by axes detection methods. Once completed, the surface reconstruction lends itself directly to 3D methods for measuring cross-sectional diameter and area. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Yim, PJ (reprint author), NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 19 TC 10 Z9 9 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3595-3 J9 PROC SPIE PY 2000 VL 3978 BP 245 EP 255 DI 10.1117/12.383404 PG 5 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28E UT WOS:000087787100025 ER PT S AU Rio, DE Rawlings, RR Hommer, DW AF Rio, DE Rawlings, RR Hommer, DW BE Chen, CT Clough, AV TI Application of a linear time invariant model in the Fourier domain to perform statistical analysis of functional magnetic resonance images SO MEDICAL IMAGING 2000: PHYSIOLOGY AND FUNCTION FORM MULTIDIMENSIONAL IMAGES SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE functional MRI; image processing; time series analysis; Fourier analysis; statistics AB A linear time invariant model is applied to functional fMRI blood flow data. This model assumes that the fMRI stochastic output sequence can be determined by a constant plus a linear filter (hemodynamic response function) of several fixed deterministic inputs and an error term, assumed stationary with zero mean and error spectrum. An on-off finger tapping experiment was performed where the subject repetitively tapped their fingers for 30 seconds and remained still for 30 seconds. Thirty three disjoint frequency bands, 3 wave numbers wide were chosen to analyze the data. At each band an F-statistical image was constructed to test (alpha = .05/33) whether power fi-om the input signal induced a response in the output signal. Activation was seen at frequency .0154Hz close to the frequency for maximum power of the input signal, .0167Hz in the contralateral motor strip and motor cortex. In conclusion, (1) No assumptions are made about the filter. (2) Several different deterministic inputs may be applied. (3) Problems with temporal correlation are avoided by performing the statistics in the Fourier domain. (4) Testing can be performed for differences in the hemodynamic transfer function at different spatial locations under different experimental conditions. C1 NIAAA, Sect Brain Electrophysiol & Imaging, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Rio, DE (reprint author), NIAAA, Sect Brain Electrophysiol & Imaging, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3595-3 J9 PROC SPIE PY 2000 VL 3978 BP 265 EP 275 DI 10.1117/12.383406 PG 3 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28E UT WOS:000087787100027 ER PT S AU Hattery, D Chernomordik, V Gannot, I Loew, M Gandjbakhche, A AF Hattery, D Chernomordik, V Gannot, I Loew, M Gandjbakhche, A BE Chen, CT Clough, AV TI Fluorescence measurement of localized, deeply embedded physiological processes SO MEDICAL IMAGING 2000: PHYSIOLOGY AND FUNCTION FORM MULTIDIMENSIONAL IMAGES SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE fluorescence; lifetime; fluorophore; photon; turbid; imaging; tissue optics; random walk; molecular tagging; diffusion ID BIOLOGICAL MEDIA; MODEL; TISSUE AB Intrinsic and exogenous fluorescent molecules may be used as specific markers of disease processes, or metabolic status. A variety of fluorescent markers have been successfully used for transparent tissue, in-vitro studies, and in cases where the markers are located close to the tissue surface. For example, given fluorescence Lifetime measurements of a fluorophore such as bis(carboxylic acid) dye, the known relationship of pH on its lifetime may be used to determine the pH of tissue at the fluorophore's location. For fluorophore depths greater than approximately one millimeter in normal tissue, such as might be encountered in in vivo studies, multiple scattering makes it impossible to make direct measurements of characteristics such as fluorophore lifetime. In a multiple scattering environment, the collected intensity depends heavily on the scattering and absorption coefficients of the tissue at both the excitation and emission frequencies. Thus, to obtain values for specific fluorophore characteristics such as the Lifetime, a theoretical description of the complex photon paths is required. We have applied Random-walk theory to successfully model photon migration in turbid media such as tissue. We show how time-resolved intensity measurements may be used to determine fluorophore location and lifetime even when the fluorophore site is located many mean photon scattering lengths from the emitter and detector. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Hattery, D (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, Bldg 12A,Room 2041, Bethesda, MD 20892 USA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3595-3 J9 PROC SPIE PY 2000 VL 3978 BP 377 EP 382 DI 10.1117/12.383419 PG 4 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28E UT WOS:000087787100039 ER PT S AU Cannata, JM Chen, WH Ritter, TA Shung, KK AF Cannata, JM Chen, WH Ritter, TA Shung, KK BE Shung, KK Insana, MF TI Fabrication of high-frequency single element ultrasonic transducers using lithium SO MEDICAL IMAGING 2000: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE ultrasonic transducers; single element; high frequency; lithium niobate AB The design and fabrication of high frequency single element ultrasonic transducers present a multitude of challenges for the transducer engineer, from size constraints to electrical impedance matching. This paper discusses the trade-offs involved in a procedure used to fabricate transducers with center frequencies in the 25MHz-100MHz range using 36 degrees rotated Y-cut lithium niobate (LiNbO3) as the active element. Transducers of varying dimensions were built according to an f-number range of 2-3.5. A lambda/4 silver epoxy matching layer with an acoustic impedance of 7.3Mrayls was used. Desired focal depths were achieved with use of an acoustic lens. Silver epoxy backing with an acoustic impedance of approximately 5.9 Mrayls was also used in all designs. All transducers were designed around a 50 Omega send and receive circuit. Electrical tuning of the transducer to the receive circuitry was achieved by using an RF transformer. All transducers were tested in a pulse-echo arrangement using a Panametrics 5900PR pulser, a Wavetek function generator and a LeCroy digital oscilloscope. The bandwidth, insertion loss, and depth of focus were measured. Several transducers were fabricated with -6dB bandwidths ranging from 62% to 74%, and two-way insertion loss values ranging from -14dB to -22dB. C1 Penn State Univ, NIH, Res Ctr Med Ultrason Transducer Engn, University Pk, PA 16802 USA. RP Cannata, JM (reprint author), Penn State Univ, NIH, Res Ctr Med Ultrason Transducer Engn, 205 Hallowell Blvd, University Pk, PA 16802 USA. NR 6 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3599-6 J9 PROC SPIE PY 2000 VL 3982 BP 86 EP 91 DI 10.1117/12.382215 PG 6 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28Q UT WOS:000087812200009 ER PT S AU Ritter, T Shung, KK Tutwiler, R Shrout, T AF Ritter, T Shung, KK Tutwiler, R Shrout, T BE Shung, KK Insana, MF TI High frequency transducer arrays for medical imaging SO MEDICAL IMAGING 2000: ULTRASONIC IMAGING AND SIGNAL PROCESSING SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2000 Conference CY FEB 13-17, 2000 CL SAN DIEGO, CA SP SPIE, Merge Technologies Inc, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, IEEE, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE transducers; piezoelectric composites; ultrasound arrays; high frequency arrays; imaging arrays ID ULTRASOUND; APERTURE; MHZ AB This paper discusses the design, fabrication, testing, and simulated imaging performance of high frequency linear arrays. Both a 2-2 PZT composite array with a fine spatial scale and a PbTiO3 array have been investigated at 30 MHz. The composite array demonstrated a seven-fold increase in sensitivity over the PbTiO3 array, as well as increased bandwidth and reduced crosstalk. The electrical impedance magnitude of the composite array was 56 ohms at 30 MHz, and the measured insertion loss was -14 dB. Simulated results demonstrate excellent lateral and axial resolution when imaging a phantom using a synthetic aperture approach. A 35 MHz device is also under development. An interconnect method using a flex circuit and sputtered metal films is used to electrically connect to each element. A curve fitting technique was then used to characterize elements of the array. Electromechanical coupling coefficients from 0.55 to 0.62 and clamped relative permittivities (epsilon(33)(S)'/epsilon(0)) from 1200 to 2000 were observed. C1 Penn State Univ, NIH, Ctr Med Ultrason Transducer Technol, University Pk, PA 16802 USA. RP Ritter, T (reprint author), Penn State Univ, NIH, Ctr Med Ultrason Transducer Technol, 205 Hallowell Bldg, University Pk, PA 16802 USA. NR 23 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3599-6 J9 PROC SPIE PY 2000 VL 3982 BP 208 EP 216 DI 10.1117/12.382227 PG 9 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BQ28Q UT WOS:000087812200024 ER PT S AU Bodenreider, O Zweigenbaum, P AF Bodenreider, O Zweigenbaum, P BE Hasman, A Blobel, B Dudeck, J Engelbrecht, R Gell, G Prokosch, HU TI Identifying proper names in parallel medical terminologies SO MEDICAL INFOBAHN FOR EUROPE, PROCEEDINGS SE STUDIES IN HEALTH TECHNOLOGY AND INFORMATICS LA English DT Proceedings Paper CT 16th Medical Informatics Europe Congress/45th Annual Congress of the German-Association-for-Medical-Informatics-Biometry-and-Epidemiology CY JUN, 2000 CL Hanover, GERMANY SP German Assoc Med Informat Biometry & Epidemiol AB We propose several criteria to identify proper names in biomedical terminologies. Traditional, pattern-based methods that rely on the immediate context of a proper name are not applicable. However, the availability of translations of some terminologies supports methods based on invariant words instead. A combination of five criteria achieved 86% precision and 88% recall on the 16,401 word forms of the International Classification of Diseases. C1 US Natl Lib Med, Bethesda, MD USA. RP Bodenreider, O (reprint author), US Natl Lib Med, Bethesda, MD USA. FU Intramural NIH HHS [Z99 LM999999] NR 8 TC 2 Z9 2 U1 0 U2 0 PU I O S PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 1-58603-063-9 J9 ST HEAL T PY 2000 VL 77 BP 443 EP 447 PG 5 WC Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BR37L UT WOS:000166218700090 PM 11187591 ER PT J AU Tiraboschi, IN Bennett, JE Kauffman, CA Rex, JH Girmenia, C Sobel, JD Menichetti, F AF Tiraboschi, IN Bennett, JE Kauffman, CA Rex, JH Girmenia, C Sobel, JD Menichetti, F TI Deep Candida infections in the neutropenic and non-neutropenic host: an ISHAM symposium SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT XIVth Congress of the International-Society-for-Human-and-Animal-Mycology CY MAY 08-12, 2000 CL BUENOS AIRES, ARGENTINA SP Int Soc Human & Anim Mycol DE Candida; candidemia; candidiasis; candiduria ID REMISSION-INDUCTION THERAPY; ACUTE MYELOID-LEUKEMIA; AMPHOTERICIN-B; CANCER-PATIENTS; RISK-FACTORS; FUNGEMIA; ENDOPHTHALMITIS; FLUCONAZOLE; MORTALITY; ALBICANS AB A symposium was held on May 8, 2000 to discuss the management of deep infections with Candida species. Among the findings discussed were the following. Candiduria is most often benign, though it occurs in patients with serious underlying diseases. Candida species are now the fourth most common cause of nosocomial bloodstream infections, usually arising from an intravenous catheter. Candida albicans represents only 50-60% of the isolates. There has been no change in the frequency of fluconazole resistance in C. albicans but some of the other species now being isolated from blood are constitutively more resistant to this drug. Nevertheless, for most non-neutropenic patients with candidemia, fluconazole is a reasonable choice for initial therapy. In the neutropenic patient, candidemia is now uncommon. Deep candida infections in neutropenic patients are usually being treated empirically with an amphotericin B formulation. Hepatosplenic candidiasis is usually detected only after recovery from neutropenia but can be suspected by imaging techniques. Improved diagnostic techniques for deep candidiasis in the neutropenic patient remain a critical requirement. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. Univ Buenos Aires, Div Infect Dis Hosp Clin, RA-1053 Buenos Aires, DF, Argentina. Vet Affairs Ann Arbor Healthcare Syst, Dept Internal Med, Div Infect Dis, Ann Arbor, MI USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Univ Texas, Sch Med, Dept Internal Med, Div Infect Dis, Houston, TX USA. Azienda Osped Pisana, Unita Operat Malattie Infett, Pisa, Italy. Univ La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, Rome, Italy. Wayne State Univ, Sch Med, Dept Internal Med, Div Infect Dis, Detroit, MI 48201 USA. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 11 Z9 14 U1 0 U2 0 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2000 VL 38 SU 1 BP 199 EP 204 DI 10.1080/mmy.38.s1.199.204 PG 6 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 401ZE UT WOS:000166958800021 PM 11204146 ER PT J AU Kwon-Chung, KJ Sorrell, TC Dromer, F Fung, E Levitz, SM AF Kwon-Chung, KJ Sorrell, TC Dromer, F Fung, E Levitz, SM TI Cryptococcosis: clinical and biological aspects SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT XIVth Congress of the International-Society-for-Human-and-Animal-Mycology CY MAY 08-12, 2000 CL BUENOS AIRES, ARGENTINA SP Int Soc Human & Anim Mycol DE Cryptococcus neoformans; genomics; immunology ID NEOFORMANS INFECTION; CYTOKINE PROFILES; VIRULENCE FACTORS; AMPHOTERICIN-B; MATING TYPES; 2 VARIETIES; MICE; IDENTIFICATION; MENINGITIS; ANTIGENS AB The incidence of cryptococcosis rose dramatically with the advent of the acquired immune deficiency syndrome (AIDS) epidemic in the early 1980s until the early 1990s. The frequency of cryptococcosis has been declining since mid 1990s in Europe and America due to the development of more effective antiretroviral therapy and prophylactic treatment regimens designed to prevent fungal infections. The disease, however, is still recognized as one of the most common life-threatening opportunistic fungal infections in immunocompromised patients, particularly among those infected with human immunodeficiency virus (HIV). For this reason, research interest in clinical and biological aspects of the disease remains high. In addition to previously embarked areas of research, the cryptococcal research community has taken advantage of the current sequencing technology and initiated genome sequencing of Cryptococcus neoformans var. neoformans. This review includes various areas of research interest ranging from pathobiology, biochemistry and immunology, to genomics. C1 NIAID, Mol Microbiol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Univ Sydney, Ctr Infect Dis & Microbiol, Sydney, NSW 2006, Australia. Inst Pasteur, Unite Mycol, Paris, France. Stanford Univ, Sequencing Ctr, Stanford, CA 94305 USA. Boston Univ Hosp, Infect Dis Sect, Boston, MA USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Clin Invest Lab, NIH, Bldg 10,11C304, Bethesda, MD 20892 USA. FU NIAID NIH HHS [U01 AI47087] NR 49 TC 61 Z9 65 U1 3 U2 5 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2000 VL 38 SU 1 BP 205 EP 213 PG 9 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 401ZE UT WOS:000166958800022 PM 11204147 ER PT J AU Graybill, JR Tollemar, J Torres-Rodriguez, JM Walsh, TJ Roilides, E Farmaki, E AF Graybill, JR Tollemar, J Torres-Rodriguez, JM Walsh, TJ Roilides, E Farmaki, E TI Antifungal compounds: controversies, queries and conclusions SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT XIVth Congress of the International-Society-for-Human-and-Animal-Mycology CY MAY 08-12, 2000 CL BUENOS AIRES, ARGENTINA SP Int Soc Human & Anim Mycol DE antifungal prophylaxis; immunomodulation; lipid-carried amphotericin B ID COLONY-STIMULATING FACTOR; INVASIVE FUNGAL-INFECTIONS; LIPOSOMAL AMPHOTERICIN-B; ACUTE MYELOID-LEUKEMIA; ASPERGILLUS-FUMIGATUS HYPHAE; BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; NEUTROPENIC PATIENTS; PULMONARY ASPERGILLOSIS; FLUCONAZOLE PROPHYLAXIS AB A new session in this Congress was the development of a discussion panel regarding controversies and queries about the main topics of treatment and prophylaxis of severe systemic mycoses. Experts presenting each side of three controversial areas provided an interchange of ideas and clarified those areas where there remain substantial disagreements. Some common recommendations have been made, and some differences persist. The contents of this session are compiled in this paper. Due to the limitations of space, this paper presents the most relevant parts of each presentation. The large and up-to-date list of references should be useful to gain a better understanding of these subjects. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Huddinge Univ Hosp, Karolinska Inst, Dept Transplantat Surg, Stockholm, Sweden. Huddinge Univ Hosp, Karolinska Inst, Dept Clin Immunol, Stockholm, Sweden. Univ Autonoma Barcelona, IMIM, Clin & Expt Mycol Grp, E-08193 Barcelona, Spain. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54006 Salonika, Greece. RP Graybill, JR (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 84 TC 13 Z9 13 U1 0 U2 0 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2000 VL 38 SU 1 BP 323 EP 333 DI 10.1080/mmy.38.s1.323.333 PG 11 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 401ZE UT WOS:000166958800034 PM 11204160 ER PT J AU Walsh, TJ Viviani, MA Arathoon, E Chiou, C Ghannoum, M Groll, AH Odds, FC AF Walsh, TJ Viviani, MA Arathoon, E Chiou, C Ghannoum, M Groll, AH Odds, FC TI New targets and delivery systems for antifungal therapy SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT XIVth Congress of the International-Society-for-Human-and-Animal-Mycology CY MAY 08-12, 2000 CL BUENOS AIRES, ARGENTINA SP Int Soc Human & Anim Mycol DE amphotericin B; drug delivery; echinocandins; triazoles ID IN-VITRO ACTIVITY; AMPHOTERICIN-B; CRYPTOCOCCUS-NEOFORMANS; CANDIDA-ALBICANS; SEMISYNTHETIC ECHINOCANDIN; MK-0991 L-743,872; DRUG-DELIVERY; PHARMACEUTICAL APPLICATIONS; PULMONARY ASPERGILLOSIS; PROLONGED CIRCULATION AB Development of new approaches for treatment of invasive fungal infections encompasses new delivery systems for approved and investigational compounds, as well as exploiting the cell membrane, cell wall and virulence factors as putative antifungal targets. Novel delivery systems consisting of cyclodextrins, cochleates, nanoparticles/nanospheres and long circulating ('stealth') liposomes, substantially modulate the pharmacokinetics of existing compounds, and may also be useful to enhance the delivery of antifungal agents to sites of infection. Further insights into the structure-activity relationship of the antifungal triazoles that target the biosynthesis of ergosterol in the fungal cell membrane have led to the development of highly potent broad spectrum agents, including posaconazole, ravuconazole and voriconazole. Similarly, a novel generation of cell-wall active semisynthetic echinocandin 1,3 beta -glucan inhibitors (caspofungin, FK463, and VER-002) has entered clinical development. These agents have potent and broad-spectrum activity against Candida spp, and potentially useful activity against Aspergillus spp. and Pneumocystis carinii. The ongoing convergence of the fields of molecular pathogenesis, antifungal pharmacology and vaccine development will afford the opportunity to develop novel targets to complement the existing antifungal armamentarium. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Inst Igiene Med Prevent, Milan, Italy. Asociac Salud Integral, Clin Familiar Luis Angel Garcia, Guatemala City, Guatemala. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Ctr Med Mycol, Cleveland, OH 44106 USA. Inst Med Sci, Dept Mol & Cell Biol, Aberdeen, Scotland. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 82 TC 96 Z9 100 U1 0 U2 12 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PY 2000 VL 38 SU 1 BP 335 EP 347 DI 10.1080/mmy.38.s1.335.347 PG 13 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 401ZE UT WOS:000166958800035 PM 11204162 ER PT S AU Peters, DC Epstein, FH McVeigh, ER AF Peters, DC Epstein, FH McVeigh, ER BE AlvaradoGil, JJ Contreras, JG Corral, GH TI Functional cardiac MR imaging SO MEDICAL PHYSICS SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 4th Mexican Symposium on Medical Physics CY MAR 01-04, 2000 CL MERIDA, MEXICO SP CINVESTAV Gen Directorate, Natl Univ, Coordinat Sci Res, Natl Univ, Phys Inst AB Undersampled projection reconstruction acquisitions are investigated for use in functional cardiac MR imaging. 256 x 256 resolution is obtainable using only 64 projections, with acceptable artifact level. Reduced FOV techniques decrease artifact. Variable angular sampling using projection reconstruction is investigated. C1 NIH, Lab Cardiac Energet, Bethesda, MD 20892 USA. RP Peters, DC (reprint author), NIH, Lab Cardiac Energet, Bldg 10, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 1-56396-963-7 J9 AIP CONF PROC PY 2000 VL 538 BP 107 EP 111 PG 5 WC Engineering, Biomedical; Physics, Applied SC Engineering; Physics GA BR18J UT WOS:000165808400012 ER PT J AU Ogryzko, V AF Ogryzko, V TI Mammalian histone acetyltransferase complexes SO MEDICINA-BUENOS AIRES LA English DT Article; Proceedings Paper CT International Symposium on New Directions in Cancer Managemet CY AUG 07-08, 2000 CL ACAD NACL MED, BUENON AIRES, ARGENTINA SP Fritz Bender Fdn, Fdn Bank Boston, Fdn Bunge & Born, Fdn Konex, Fdn Perez Companc, Fdn Rene Baron, Fdn Roemmers, Fdn Telefon Argentina, Gador SA, Gautier SA, Inst Sidus SA, John Wyeth Lab SA, Kampel Martian Asta Med SA, Labs Filaxis SA, Nestle SA, Novartis SA, Omint SA, Prod Roche SA, Qualitas SA, WestDeutsch Landesbank, Girozentrale, Duesseldorf HO ACAD NACL MED DE chromatin; acetylation; proteome; transcription; apoptosis ID TRANSCRIPTIONAL REGULATION; CORE; CHROMATIN; PROTEIN; ACETYLATION; OCTAMER; TIP60; TAFS AB Over the last decade, great progress has been made in elucidating how the human genome operates in the chromatin context. This paper describes our work on two human acetyltransferases, PCAF and TIP60, and their interaction partners. This study provides new clues on the function of these enzymes. In a striking parallel with the general transcription factor TFIID, PCAF complex contains proteins that have histone-like domains. We speculate that these subunits can presumably form a nucleosome-like structure on DNA, which would allow PCAF to contribute to the maintenance of an active state of chromatin. On the other hand, TIP60 complex contains two eukaryotic homologs of bacterial RuvB helicase/ATPse, involved in recombination and repair. Accordingly, expression of a dominant negative mutant of TIP60 in living cells interferes with their ability to repair DNA damage, which points out, for the first time, a role for a histone acetyltransferase in a process other than transcription. We also have evidence implicating TIP60 in the apoptotic response to DNA damage. C1 NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Ogryzko, V (reprint author), NICHD, Lab Mol Growth Regulat, NIH, 9000 Rockville Pike,Bldg 6,Rm 416, Bethesda, MD 20892 USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 30 TC 2 Z9 2 U1 0 U2 0 PU MEDICINA (BUENOS AIRES) PI BUENOS AIRES PA DONATO ALVAREZ 3150, 1427 BUENOS AIRES, ARGENTINA SN 0025-7680 J9 MEDICINA-BUENOS AIRE JI Med.-Buenos Aires PY 2000 VL 60 SU 2 BP 21 EP 26 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 373WQ UT WOS:000165313400007 PM 11188926 ER PT J AU Yuspa, SH Hansen, L Li, LW Joseloff, E Weinberg, W Fernandez-Salas, E AF Yuspa, SH Hansen, L Li, LW Joseloff, E Weinberg, W Fernandez-Salas, E TI Interacting signaling pathways in the pathogenesis of squamous cell carcinoma SO MEDICINA-BUENOS AIRES LA English DT Article; Proceedings Paper CT XLV Scientific Meeting of the Argentine-Society-of-Clinical-Investigation/XLVIII Scientific Meeting of the Argentine-Society-of-Immunology CY NOV 22-25, 2000 CL MAR DEL PLATA, ARGENTINA SP Argentine Soc Clin Investigat, Argentine Soc Immunol ID GROWTH-FACTOR RECEPTOR; KINASE-C-DELTA; FACTOR-ALPHA; TYROSINE PHOSPHORYLATION; EPIDERMAL-KERATINOCYTES; MALIGNANT CONVERSION; TARGETED DISRUPTION; SKIN CARCINOGENESIS; V-RAS(HA) ONCOGENE; P53 LOSS C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NR 26 TC 1 Z9 2 U1 0 U2 0 PU MEDICINA (BUENOS AIRES) PI BUENOS AIRES PA DONATO ALVAREZ 3150, 1427 BUENOS AIRES, ARGENTINA SN 0025-7680 J9 MEDICINA-BUENOS AIRE JI Med.-Buenos Aires PY 2000 VL 60 IS 5 BP 689 EP 692 PN 2 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 382DM UT WOS:000165804000007 PM 11188883 ER PT J AU Thorgeirsson, SS AF Thorgeirsson, SS TI Molecular and cellular biology of hepatic stem cells SO MEDICINA-BUENOS AIRES LA English DT Article; Proceedings Paper CT XLV Scientific Meeting of the Argentine-Society-of-Clinical-Investigation/XLVIII Scientific Meeting of the Argentine-Society-of-Immunology CY NOV 22-25, 2000 CL MAR DEL PLATA, ARGENTINA SP Argentine Soc Clin Investigat, Argentine Soc Immunol C1 NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDICINA (BUENOS AIRES) PI BUENOS AIRES PA DONATO ALVAREZ 3150, 1427 BUENOS AIRES, ARGENTINA SN 0025-7680 J9 MEDICINA-BUENOS AIRE JI Med.-Buenos Aires PY 2000 VL 60 IS 5 BP 693 EP 693 PN 2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 382DM UT WOS:000165804000008 ER PT J AU May, EL Aceto, MD Bowman, ER Traynor, JR Woods, JH Jacobson, AE Harris, LS AF May, EL Aceto, MD Bowman, ER Traynor, JR Woods, JH Jacobson, AE Harris, LS TI Enantiomeric (-)-(1R,5R,9R) and (+)-(1S,5S,9S) heterocyclic N-substituted-normetazocines: Synthesis of potent and selective antinociceptives and opioid antagonists through N-substituent modification SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article ID ANALGESICS; MEMBRANES; AGONISTS; BINDING AB A number of diverse N-substituted-N-normetazocine heterocycles ((-)-1R,5R,9R)- and (+)-(1S,5S,9S)-5,9-dimethyl-2'-hydroxy-2-substituted-6,7-benzomorphans) were synthesized and evaluated. Conversion of an antinociceptively inactive alcohol to an ether (-)-1R,5R,9R)-5,9-dimethyl-2'-hydroxy-2(2-methoxyethyl)-6,7-benzomorphan ((-)-N-methoxyethylnormetazocine, 4), gave a compound that was 10 to 40 times more potent than morphine as an antinociceptive agent, but did not attenuate morphine withdrawal in monkeys. Other (-)-enantiomers also had patent antinociceptive activity and one, (-)-N-fluoropropylnormetazocine (9), was a potent opioid antagonist. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol, Richmond, VA 23298 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20894 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. RP May, EL (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol, Richmond, VA 23298 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PY 2000 VL 10 IS 3 BP 178 EP 185 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 373QN UT WOS:000165300500004 ER PT J AU Yu, QS Greig, NH Holloway, HW Flippen-Anderson, JL Brossi, A AF Yu, QS Greig, NH Holloway, HW Flippen-Anderson, JL Brossi, A TI (-)-(3aS)-eseroline carbamate (II), a potent cholinesterase inhibitor and close analogue of physostigmine: Reanalysis SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article ID ALZHEIMERS-DISEASE; (-)-ESEROLINE; PHENSERINE AB (-)-Eseroline 8 on reaction with trimethylsilyl isocyanate in refluxing toluene directly gave the crystalline tricyclic urea 2. Carbamate 1 was made by debenzylation of 2',4'-dimethoxybenzylcarbamate 17. The structures of carbamate 1 and tricyclic urea 2 were confirmed by X-ray crystallography. Carbamate 1, like physostigmine, was found to possess high inhibitory activity against human acetyl- (AChE) and butyrylcholinesterase (BChE) in vitro and potent action when administered to rats in in vivo studies. C1 NIA, Neurosci Lab, Gerontol Res Ctr 4B02, Intramural Res Program,NIH, Baltimore, MD 21224 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA. RP Greig, NH (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr 4B02, Intramural Res Program,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 24 TC 3 Z9 3 U1 1 U2 2 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PY 2000 VL 10 IS 3 BP 186 EP 199 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 373QN UT WOS:000165300500005 ER PT J AU Csako, G Byrd, D Wesley, RA Sarlis, NJ Skarulis, MC Nieman, LK Pucino, F AF Csako, G Byrd, D Wesley, RA Sarlis, NJ Skarulis, MC Nieman, LK Pucino, F TI Assessing the effects of thyroid suppression on benign solitary thyroid nodules - A model for using quantitative research synthesis SO MEDICINE LA English DT Article ID FINE-NEEDLE ASPIRATION; L-THYROXINE; MYOCARDIAL-INFARCTION; MEDICAL-TREATMENT; RANDOMIZED TRIAL; NONTOXIC GOITER; DRUG-THERAPY; BONE-DENSITY; DOUBLE-BLIND; LEVOTHYROXINE C1 NCI, Dept Clin Pathol, NIH, Bethesda, MD 20892 USA. NCI, Dept Pharm, NIH, Bethesda, MD 20892 USA. NCI, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Csako, G (reprint author), NIH, Dept Clin Pathol, Ctr Clin, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. NR 89 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2000 VL 79 IS 1 BP 9 EP 26 DI 10.1097/00005792-200001000-00002 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 278MM UT WOS:000084993600002 PM 10670406 ER PT B AU Sherman, SS Goldstein, RE Crawford, SL Ory, M Guralnik, JM AF Sherman, SS Goldstein, RE Crawford, SL Ory, M Guralnik, JM BE Aso, T Yanaihara, T Fujimoto, S TI Menopause and six chronic conditions of aging: the Study of Women's Health Across the Nation (SWAN) SO MENOPAUSE AT THE MILLENNIUM LA English DT Proceedings Paper CT 9th World Congress on the Menopause CY OCT 17-21, 1999 CL YOKOHAMA, JAPAN SP Int Menopause Soc C1 NIA, NIH, Bethesda, MD 20892 USA. RP Sherman, SS (reprint author), NIA, NIH, Gateway Bldg,Suite 3E327,7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND BN 1-85070-709-X PY 2000 BP 117 EP 121 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BQ99L UT WOS:000165310100015 ER PT J AU Bellino, FL AF Bellino, FL TI Nonprimate animal models of menopause: Workshop report SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE animal models; dog; nonprimate; rabbit; rodent; pig; sheep ID E-DEFICIENT MICE; FATTY STREAK FORMATION; REPLACEMENT THERAPY; OVARIAN-FUNCTION; BONE METABOLISM; RHESUS-MONKEYS; BEAGLE DOGS; RAT MODEL; ESTROGEN; ATHEROSCLEROSIS AB Objective: Menopause, an understudied, normal biological process in middle-aged women, is associated with loss of fertility and increased risk for osteoporosis and cardiovascular disease. Appropriate animal models allow in-depth investigation of biological mechanisms that underlie the increased risk for adverse health events in menopausal women, Although some species of older female nonhuman primates experience a menopause-like condition, with cessation of reproductive cycles, decreased bone density, and perhaps an increased risk for atherosclerosis, several factors restrict their usefulness for research (e.g,, expense of purchase and care, relatively small numbers of animals available, risk for disease transmission to humans, limited facilities fur experimentation). Thus, it may be useful to consider nonprimate animal species as potential models for pathophysiological changes associated with loss of reproductive function. Design: A workshop was convened in June 1998 at the National Institutes of Health to explore the suitability of nonprimate animal species in this context. The focus of this workshop was on middle-aged, ovariectomized females of various laboratory animal species and the ability of exogenous estrogen to reverse pathophysiological changes in the skeleton, cardiovascular system, and thermoregulatory control mechanisms in these species, Conclusions: Of the species considered (mice, rats, dogs, rabbits, pigs, and sheep) and because of the limitations of relatively small amounts of research in ovariectomized, middle-aged animals for most of these species, mice (largely because of transgenic technology) have the potential to be good models for the effect of ovariectomy and estrogen replacement on associated bone and cardiovascular changes. Rats are an excellent model for bone but a poor model for the cardiovascular system changes associated with loss of reproductive function. Usefulness of the pig, which is usually considered to be a good model for the human cardiovascular system, is limited by the dearth of information available on ovariectomized mature pigs in cardiovascular and bone studies, sensitivity of bone density to dietary calcium, the difficult-to-manage size of regular pigs, and the relatively high cost of minipigs. Rabbits show good potential as a cardiovascular model despite the limited numbers of studies and the difference from primates in coronary artery structure, Although rabbits are the smallest species known to have Haversian bone remodeling processes, the limited number of bone studies in ovariectomized rabbits is confounded by effects of dietary calcium. Although there are virtually no studies on the cardiovascular system of the ovariectomized dog, bone studies that have been conducted suggest that it is a poor model for the menopausal human. Furthermore, the role of estrogen in bone and cardiovascular physiology is difficult to interpret because of the limitation of two estrus cycles per year in the dog. The sheep seems to be a promising large animal model for the bone and cardiovascular systems, but more research is needed. Of the species examined for estrogen effects on vasomotor symptoms (guinea pig, mouse, rat, and monkey), only rats and monkeys show evidence of hot flashes associated with loss of reproductive function. (Menopause 2000;7:14-24. (C) 2000, The North American Menopause Society.). C1 NIA, Biol Aging Program, Bethesda, MD 20892 USA. RP Bellino, FL (reprint author), NIA, Biol Aging Program, Gateway Bldg,Suite 2C231, Bethesda, MD 20892 USA. NR 53 TC 57 Z9 63 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD JAN-FEB PY 2000 VL 7 IS 1 BP 14 EP 24 DI 10.1097/00042192-200007010-00004 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 273QK UT WOS:000084718200004 PM 10646699 ER PT J AU Muenke, M Cohen, MM AF Muenke, M Cohen, MM TI Genetic approaches to understanding brain development: Holoprosencephaly as a model SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE brain development; holoprosencephaly; Sonic Hedgehog gene ID LEMLI-OPITZ-SYNDROME; MURINE HOMEOBOX GENE; SONIC-HEDGEHOG; RETINOIC ACID; CRITICAL REGION; DELTA-7-STEROL REDUCTASE; MUTATIONS; EXPRESSION; MOUSE; DROSOPHILA AB Holoprosencephaly (HPE) is the most common major developmental defect of the forebrain in humans. Clinical expression is variable, ranging from a small brain with a single cerebral ventricle and cyclopia to clinically unaffected carriers in familial HPE. Significant etiologic heterogeneity exists in HPE and includes both genetic and environmental causes. Defects in the cell signaling pathway involving the Sonic Hedgehog (SHH) gene, as well as defects in the cholesterol biosynthesis have been shown to cause HPE in humans. More recently, HPE genes from additional signaling pathways have been identified. These discoveries and current genetic approaches serve asa paradigm for studying normal and abnormal brain morphogenesis. (C) 2000 Wiley-Liss, Inc. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. Dalhousie Univ, Hlth Serv Adm Sociol & Social Anthropol, Dept Oral & Maxillofacial Surg, Halifax, NS, Canada. Dalhousie Univ, Hlth Serv Adm Sociol & Social Anthropol, Dept Pediat, Halifax, NS, Canada. Dalhousie Univ, Hlth Serv Adm Sociol & Social Anthropol, Dept Epidemiol & Community Hlth, Halifax, NS, Canada. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, Bldg 10,10C101, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD28732, HD29862] NR 73 TC 45 Z9 45 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2000 VL 6 IS 1 BP 15 EP 21 DI 10.1002/(SICI)1098-2779(2000)6:1<15::AID-MRDD3>3.0.CO;2-8 PG 7 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 290XM UT WOS:000085703200003 PM 10899793 ER PT J AU Tierney, E Nwokoro, NA Kelley, RI AF Tierney, E Nwokoro, NA Kelley, RI TI Behavioral phenotype of RSH/Smith Lemli-Opitz syndrome SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE cholesterol; genetic disorder; autistic disorder; Autism Diagnostic Interview-Revised (ADI-R); Sensory Profile ID DEFECTIVE CHOLESTEROL-BIOSYNTHESIS; SENSORY PROFILE; CHILDREN; AUTISM; DISABILITIES; PERFORMANCE AB Smith-Lemli-Opitz syndrome (SLOS, RSH/SLO syndrome, MIM 270400) is an autosomal recessive multiple malformation/mental retardation syndrome initially described by Smith et al. [1964] that is due to a defect in cholesterol biosynthesis. The behavioral phenotype of Smith-Lemli-Opitz syndrome demonstrates cognitive abilities from borderline intellectual functioning to profound mental retardation, sensory hyperreactivity, irritability, language impairment, sleep cycle disturbance, self-injurious behavior, and autism spectrum behaviors. In a recent study of 28 subjects, 14 subjects (50%) with SLOS also exhibited the behavior of throwing themselves backward in a characteristic upper body movement ("opisthokinesis") and 2 adolescents had a stretching motion of the upper body accompanied by hand flicking [Tierney et al., 1999]. In that same study, 6 of 13 subjects (46%) met the Autism Diagnostic Interview-Revised (ADI-R) algorithm criteria (Lord et al. [1993] infant Mental Health 14:234-252; Lord et al. [1994] J Autism Dev Disord 24:659-685) and the Diagnostic and Statistical Manual (APA [1994] DSM-IV) diagnostic criteria for autistic disorder. Smith-Lemli-Opitz syndrome is a metabolic disorder that is associated with autism. (C) 2000 Wiley-Liss, Inc. C1 Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Kennedy Krieger Inst, Div Intermediary Metab, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. RP Tierney, E (reprint author), Kennedy Krieger Inst, Dept Psychiat, 1750 E Fairmount Ave, Baltimore, MD 21231 USA. NR 29 TC 46 Z9 46 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2000 VL 6 IS 2 BP 131 EP 134 DI 10.1002/1098-2779(2000)6:2<131::AID-MRDD7>3.0.CO;2-R PG 4 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 321JB UT WOS:000087451400007 PM 10899806 ER PT J AU Rumsey, JM Ernst, M AF Rumsey, JM Ernst, M TI Functional neuroimaging of autistic disorders SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE autism; autistic disorder; Asperger's disorder; functional neuroimaging; PET; SPECT; MRS; MEG; FMRI ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE SPECTROSCOPY; SEROTONIN SYNTHESIS CAPACITY; INFANTILE-AUTISM; CHILDHOOD AUTISM; GLUCOSE-METABOLISM; IN-VIVO; MAGNETOENCEPHALOGRAPHIC PATTERNS; EPILEPTIFORM ACTIVITY AB Functional neuroimaging methods hold promise for elucidating the neurobiology of autistic disorders, yet they present difficult practical and scientific challenges when applied to these complex and heterogeneous syndromes. Single-state studies of brain metabolism and blood flow thus far have failed to yield consistent findings, but suggest considerable variability in regional patterns of cerebral synaptic activity. Patients with idiopathic autism are less likely to show abnormalities than are patients with comorbid illness or epilepsy. Activation studies have begun to suggest alterations in brain organization for language and cognition. Neurotransmitter studies using positron emission tomography (PET) suggest abnormalities of serotonergic acid dopaminergic function. Studies using magnetic resonance spectroscopy (MRS) have begun to document metabolic deficits in the frontal cortex and cerebellum. A single study using magnetoencephalography suggests a high incidence of epileptiform activity in children with autistic regression. Research needs include well-controlled developmental studies, particularly of young subjects and relatively homogeneous subgroups, which balance scientific rigor with ethical constraints. Investigations of the serotonergic and dopaminergic systems, limbic-based memory and emotional systems, and the role of epileptiform activity in autism represent priorities for future research. Published 2000 Wiley-Liss, Inc.(dagger) C1 NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. NIDA, Brain Imaging Ctr, Bethesda, MD 20892 USA. RP Rumsey, JM (reprint author), NIMH, Clin Neurosci Branch, 6001 Execut Blvd,Room 7175,MSC 9639, Bethesda, MD 20892 USA. NR 64 TC 55 Z9 57 U1 2 U2 14 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2000 VL 6 IS 3 BP 171 EP 179 DI 10.1002/1098-2779(2000)6:3<171::AID-MRDD4>3.0.CO;2-N PG 9 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 349ZM UT WOS:000089075600004 PM 10982494 ER PT J AU Gaillard, WD AF Gaillard, WD TI Structural and functional imaging in children with partial epilepsy SO MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS LA English DT Review DE MRI; PET; fMRI; complex partial epilepsy; children ID TEMPORAL-LOBE EPILEPSY; POSITRON-EMISSION-TOMOGRAPHY; COMPLEX PARTIAL SEIZURES; COMPUTED-TOMOGRAPHY; LANGUAGE DOMINANCE; FDG-PET; HIPPOCAMPAL ATROPHY; BLOOD-FLOW; ELECTROCORTICAL STIMULATION; REGIONAL HYPOMETABOLISM AB Imaging plays an increasingly important role in the evaluation of children with complex partial seizures. Most partial epilepsy, especially of temporal lobe origin, begins during childhood. Structural imaging with high-resolution MRI can help identify the etiology of partial seizure disorders in many children. MRI studies also show the more widespread effect of seizures on brain structure. Progressive volume loss of the hippocampal formation in some patients with temporal lobe epilepsy provides evidence that continued seizures may be associated with progressive neuronal injury. FDC-PET studies show regional decreases in glucose consumption in the cortical zone from which seizures arise. Functional abnormalities often are more extensive than the seizure focus. Studies in children with recent-onset epilepsy show that metabolic abnormalities are considerably less common than in adults with partial epilepsy, supporting the notion that in some patients there may be progressive metabolic changes that occur with continued seizures. Functional MRI may be used to identify language areas in children with partial epilepsy. fMRI language tasks reliably identify the dominant hemisphere for language dominance when compared to the intracarotid amytal procedure. Tests of verbal fluency and semantic decision identify frontal lobe language areas, while reading text paradigms and auditory passage paradigms are better for identifying temporal language areas. A panel of paradigms is best used to identify language areas in children being considered for epilepsy surgery. fMRI is a valuable tool for elucidating the impact of chronic neurologic disease stales on the functional organization of language networks during development. Published 2000 Wiley-Liss, Inc.(dagger) C1 George Washington Univ, Childrens Natl Med Ctr, Dept Neurol, Sch Med, Washington, DC 20010 USA. NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Gaillard, WD (reprint author), George Washington Univ, Childrens Natl Med Ctr, Dept Neurol, Sch Med, 111 Michigan Ave NW, Washington, DC 20010 USA. FU NINDS NIH HHS [KO8 NS01663] NR 92 TC 6 Z9 7 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1080-4013 J9 MENT RETARD DEV D R JI Ment. Retard. Dev. Disabil. Res. Rev. PY 2000 VL 6 IS 3 BP 220 EP 226 PG 7 WC Clinical Neurology; Neurosciences; Pediatrics; Psychiatry SC Neurosciences & Neurology; Pediatrics; Psychiatry GA 349ZM UT WOS:000089075600010 PM 10982500 ER PT B AU Chefer, SI Mukhin, AG Horti, AG Koren, AO Pavlova, OI Kurian, V Stratton, M Kimes, AS AF Chefer, SI Mukhin, AG Horti, AG Koren, AO Pavlova, OI Kurian, V Stratton, M Kimes, AS BE Valafar, F TI 2-[F-18]Fluoro-A-85380: A novel pet ligand for nicotinic acetylcholine receptors SO METMBS'00: PROCEEDINGS OF THE INTERNATIONAL CONFERENCE ON MATHEMATICS AND ENGINEERING TECHNIQUES IN MEDICINE AND BIOLOGICAL SCIENCES, VOLS I AND II LA English DT Proceedings Paper CT International Conference on Mathematics and Engineering Techniques in Medicine and Biological Sciences (METMBS 00) CY JUN 26-29, 2000 CL LAS VEGAS, NV SP Comp Sci, Res, Educ & Applicat Press, Int Technol Inst, Korea Informat Processing Soc, PDPTA DE PET; nicotinic acetylcholine receptors; neuroimaging; non-human primates ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; RADIOIODINATED ANALOG; EPIBATIDINE; BINDING; ALZHEIMER; BRAIN; RADIOTRACER; DISEASE AB The density of brain nicotinic acetylcholine receptors (nAChRs) in Rhesus monkey was measured in vivo by PET with 2-[F-18]fluoro-3-(2(S)-azetidinylmethoxy (2-[F-18]Fluoro-A-85380). The results of blocking studies with cytisine suggested the use of cerebellum for estimation of non-specific ligand accumulation in the thalamus. Therefore, the specific binding (SB) was measured as a difference between the total radioactivity in the thalamus and that in the cerebellum. The saturation of 2-fluoro-A-85380 SE in the thalamus was analyzed on the same animal by administering different masses of the ligand. Our results demonstrated that the SE in the thalamus was saturable. The ligand at a dose of 70 nmol/kg occupied 85% of nAChRs and at a dose of ca. 8.7 nmol/kg (ED50) 50% of nAChRs Using Scatchard analysis, the density of nAChRs in Rhesus monkey thalamus in vivo was calculated as ca. 5.5 pmol/g tissue. This value was in close agreement with estimates from in vitro assays of Rhesus monkey brain tissue. C1 NIDA, Brain Imaging Ctr, NIH, Baltimore, MD 21224 USA. RP Chefer, SI (reprint author), NIDA, Brain Imaging Ctr, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 19 TC 2 Z9 2 U1 0 U2 1 PU C S R E A PRESS PI ATHENS PA 115 AVALON DR, ATHENS, GA 30606 USA BN 1-892512-62-9 PY 2000 BP 409 EP 415 PG 7 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematics, Interdisciplinary Applications SC Computer Science; Engineering; Mathematics GA BR81W UT WOS:000167662700061 ER PT B AU Mukhin, AG Chefer, SI Horti, AG Koren, AO Vaupel, DB Gundisch, D Pavlova, OA Stratton, M Kurian, V Kimes, AS London, ED AF Mukhin, AG Chefer, SI Horti, AG Koren, AO Vaupel, DB Gundisch, D Pavlova, OA Stratton, M Kurian, V Kimes, AS London, ED BE Valafar, F TI Radiohalogenated analogs of A-85380 as potential ligands for in vivo monitoring of the alpha 4 beta 2 nicotinic receptor alteration in Alzheimer's disease SO METMBS'00: PROCEEDINGS OF THE INTERNATIONAL CONFERENCE ON MATHEMATICS AND ENGINEERING TECHNIQUES IN MEDICINE AND BIOLOGICAL SCIENCES, VOLS I AND II LA English DT Proceedings Paper CT International Conference on Mathematics and Engineering Techniques in Medicine and Biological Sciences (METMBS 00) CY JUN 26-29, 2000 CL LAS VEGAS, NV SP Comp Sci, Res, Educ & Applicat Press, Int Technol Inst, Korea Informat Processing Soc, PDPTA ID POSITRON-EMISSION-TOMOGRAPHY; ACETYLCHOLINE-RECEPTORS; IN-VIVO; BINDING-SITES; RADIOIODINATED ANALOG; PARKINSONS-DISEASE; CEREBRAL-CORTEX; BRAIN; RADIOLIGAND; PET AB Postmortem studies have revealed dramatic losses of nicotinic acetylcholine receptors (nAChRs) in the brains of patients with Alzheimer's disease (AD). As loss of nAChRs may be an early marker for neurodegeneration in AD, noninvasive in vivo assays of nAChRs might be useful for diagnosis. In an effort to develop selective radioligands for imaging nAChRs in vivo, we synthesized a series of radiohalogenated analogs of 3-(2(S)-azetidinylmethoxy)pyridine (A-85380). These compounds include 5-[I-123/125]iodo, 2-[F-18]fluoro, and 6-[F-18]fluoro derivatives, with the halogen incorporated into the 3-pyridyl moiety. In vitro and in vivo studies demonstrated that these ligands had low toxicity as well as high affinity and high selectivity for the alpha4 beta2 nAChR subtype, one of the two most abundant varieties of nAChRs in mammalian brain. Studies in non-human primates showed that these radioligands; can be used for in vivo quantification of alpha4 beta2 nAChRs. Taken together, these results suggest that radiohalogenated analogs of A-85380 represent promising probes for in vivo imaging of the alpha4 beta2 subtype of nAChRs in human brain. C1 NIDA, Brain Imaging Ctr, NIH, Baltimore, MD 21224 USA. RP Mukhin, AG (reprint author), NIDA, Brain Imaging Ctr, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 45 TC 0 Z9 0 U1 0 U2 1 PU C S R E A PRESS PI ATHENS PA 115 AVALON DR, ATHENS, GA 30606 USA BN 1-892512-62-9 PY 2000 BP 429 EP 435 PG 7 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematics, Interdisciplinary Applications SC Computer Science; Engineering; Mathematics GA BR81W UT WOS:000167662700065 ER PT S AU Chalmers, JM Everall, NJ Schaerberle, MD Levin, IW Lewis, EN Kidder, LH Pearson, M Chesters, MA Bozec, L Pollock, HM Hammiche, A AF Chalmers, JM Everall, NJ Schaerberle, MD Levin, IW Lewis, EN Kidder, LH Pearson, M Chesters, MA Bozec, L Pollock, HM Hammiche, A BE Williams, DB Shimizu, R TI FTIR-microspectroscopy of polymers advances into the 21(st) century! SO MICROBEAM ANALYSIS 2000, PROCEEDINGS SE INSTITUTE OF PHYSICS CONFERENCE SERIES LA English DT Article; Proceedings Paper CT 2nd Conference of the International-Union-of-Microbeam-Analysis-Societies CY JUL 09-14, 2000 CL KAILUA KONA, HAWAII SP Australian Microbeam Anal Soc, Brasilian Soc Microscopy & Microanal, Microscopy Soc Canada, China Joint Comm Microbeam Anal, European Microbeam Anal Soc, Japan Soc Promot Sci, Comm 141 Microbeam Anal, Korean Soc Electron Microscopy, Microbeam Anal Soc ID MICROSCOPY C1 VSConsulting, Stokesley TS9 5NW, England. ICI Technol, Wilton Res Ctr, Middlesbrough TS90 8JE, Cleveland, England. NIH, Chem Phys Lab, Bethesda, MD 20892 USA. Spectral Dimens Inc, Olney, MD 20832 USA. Univ Nottingham, Fac Sci, Sch Chem, Nottingham NG7 2RD, England. Univ Lancaster, Sch Phys & Chem, Lancaster LA1 4YB, England. RP Chalmers, JM (reprint author), VSConsulting, 14 Croft Hills,Tame Bridge, Stokesley TS9 5NW, England. NR 5 TC 0 Z9 0 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TECHNO HOUSE, REDCLIFFE WAY, BRISTOL, ENGLAND BS1 6NX SN 0951-3248 BN 0-7503-0685-8 J9 INST PHYS CONF SER PY 2000 IS 165 BP 41 EP 42 PG 2 WC Instruments & Instrumentation; Microscopy; Physics, Multidisciplinary; Spectroscopy SC Instruments & Instrumentation; Microscopy; Physics; Spectroscopy GA BR57H UT WOS:000166835400021 ER PT S AU Lewis, EN Haka, AS Levin, IW Kidder, LH AF Lewis, EN Haka, AS Levin, IW Kidder, LH BE Williams, DB Shimizu, R TI New applications and analytical methods for vibrational spectroscopic imaging SO MICROBEAM ANALYSIS 2000, PROCEEDINGS SE INSTITUTE OF PHYSICS CONFERENCE SERIES LA English DT Article; Proceedings Paper CT 2nd Conference of the International-Union-of-Microbeam-Analysis-Societies CY JUL 09-14, 2000 CL KAILUA KONA, HAWAII SP Australian Microbeam Anal Soc, Brasilian Soc Microscopy & Microanal, Microscopy Soc Canada, China Joint Comm Microbeam Anal, European Microbeam Anal Soc, Japan Soc Promot Sci, Comm 141 Microbeam Anal, Korean Soc Electron Microscopy, Microbeam Anal Soc C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Spectral Dimens Inc, Olney, MD 20832 USA. RP Lewis, EN (reprint author), Spectral Dimens Inc, 3403 Olandwood Court,Suite 102, Olney, MD 20832 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TECHNO HOUSE, REDCLIFFE WAY, BRISTOL, ENGLAND BS1 6NX SN 0951-3248 BN 0-7503-0685-8 J9 INST PHYS CONF SER PY 2000 IS 165 BP 73 EP 74 PG 2 WC Instruments & Instrumentation; Microscopy; Physics, Multidisciplinary; Spectroscopy SC Instruments & Instrumentation; Microscopy; Physics; Spectroscopy GA BR57H UT WOS:000166835400037 ER PT S AU Leapman, RD Andrews, SB AF Leapman, RD Andrews, SB BE Williams, DB Shimizu, R TI Strategies for optimizing detection limits in elemental mapping of biological specimens by electron energy-loss spectrum-imaging SO MICROBEAM ANALYSIS 2000, PROCEEDINGS SE INSTITUTE OF PHYSICS CONFERENCE SERIES LA English DT Article; Proceedings Paper CT 2nd Conference of the International-Union-of-Microbeam-Analysis-Societies CY JUL 09-14, 2000 CL KAILUA KONA, HAWAII SP Australian Microbeam Anal Soc, Brasilian Soc Microscopy & Microanal, Microscopy Soc Canada, China Joint Comm Microbeam Anal, European Microbeam Anal Soc, Japan Soc Promot Sci, Comm 141 Microbeam Anal, Korean Soc Electron Microscopy, Microbeam Anal Soc ID EELS C1 NIH, ORS, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Leapman, RD (reprint author), NIH, ORS, Div Bioengn & Phys Sci, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TECHNO HOUSE, REDCLIFFE WAY, BRISTOL, ENGLAND BS1 6NX SN 0951-3248 BN 0-7503-0685-8 J9 INST PHYS CONF SER PY 2000 IS 165 BP 185 EP 186 PG 2 WC Instruments & Instrumentation; Microscopy; Physics, Multidisciplinary; Spectroscopy SC Instruments & Instrumentation; Microscopy; Physics; Spectroscopy GA BR57H UT WOS:000166835400093 ER PT J AU Chida, T Okamura, N Ohtani, K Yoshida, Y Arakawa, E Watanabe, H AF Chida, T Okamura, N Ohtani, K Yoshida, Y Arakawa, E Watanabe, H TI The complete DNA sequence of the O antigen gene region of Plesiomonas shigelloides serotype O17 which is identical to Shigella sonnei form I antigen SO MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Plesiomonas shigelloides O17; Shigella sonnei form I; rfb gene cluster; O antigen ID ESCHERICHIA-COLI; MOLECULAR-CLONING; SALMONELLA-TYPHIMURIUM; LIPOPOLYSACCHARIDE; BIOSYNTHESIS; RESISTANCE; PLASMIDS; POLYSACCHARIDE; IMMUNIZATION; PROTECTION AB We cloned and determined the sequence of a DNA region of approximately 15-kb containing the cluster of genes required for O17 antigen expression in the Escherichia coli K-12 strain from the chromosome of Plesiomonas shigelloides serotype O17:H2 strain. The sequencing analysis revealed that the minimum essential region of the P. shigelloides O17 antigen gene cluster had a size of approximately 11.5-kb and contained 9 contiguous open reading frames (ORFs), which were almost identical to the corresponding ORFs of Shigella sonnei form I antigen gene region, except for 1S630 sequence, at the DNA as well as amino acid levels. The putative function of most of the ORFs could be determined on the basis of amino acid sequence similarities and characteristics. In addition, the G + C content of the P. shigelloides O17 antigen genes was lower than that of the chromosomal DNA of P. shigelloides and S. sonnei, suggesting that both P. shigelloides O17 and S. sonnei form I antigen genes had been derived from the same origin with a low G + C content. C1 Tokyo Med & Dent Univ, Sch Allied Hlth Sci, Fac Med, Dept Clin Microbiol & Immunol,Bunkyo Ku, Tokyo 1138519, Japan. Tokyo Med & Dent Univ, Human Gene Sci Ctr, Bunkyo Ku, Tokyo 1138519, Japan. Inst Publ Hlth, Dept Microbiol, Minato Ku, Tokyo 1080071, Japan. NIAID, Dept Bacteriol, Shinjuku Ku, Tokyo 1628640, Japan. RP Okamura, N (reprint author), Tokyo Med & Dent Univ, Sch Allied Hlth Sci, Fac Med, Dept Clin Microbiol & Immunol,Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138519, Japan. NR 39 TC 8 Z9 10 U1 0 U2 1 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 4-16 YAYOI 2-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0385-5600 J9 MICROBIOL IMMUNOL JI Microbiol. Immunol. PY 2000 VL 44 IS 3 BP 161 EP 172 PG 12 WC Immunology; Microbiology SC Immunology; Microbiology GA 291QY UT WOS:000085748600002 PM 10789503 ER PT J AU Elster, EA Blair, PJ Kirk, AD AF Elster, EA Blair, PJ Kirk, AD TI Potential of costimulation-based therapies for composite tissue allotransplantation SO MICROSURGERY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Composite Tissue Allotransplantation CY MAY 17-18, 2000 CL LOUISVILLE, KENTUCKY ID DONOR-SPECIFIC TRANSFUSION; RENAL-ALLOGRAFT REJECTION; MONOCLONAL-ANTIBODY; T-HELPER; SKIN; CD40; CELL; TRANSPLANTATION; TOLERANCE; ISLET AB Clinical success has not been routinely achieved for composite tissue allotransplantation (CTA). Although most of the technical details of CTA have been overcome, the immunological aspects of these procedures have proved complex. Many traumatic conditions requiring CTA contraindicate acute global immunosuppression. Moreover, the risk of longterm immunosuppression is difficult to reconcile with non-life-threatening defects that can be adequately palliated. Recently, several successful immunomodulating strategies have been introduced for solid organ transplantation. They include therapies that alter costimulatory signals at engraftment. One approach, using treatment with a monoclonal antibody directed against CD154, has shown promise in rodent and nonhuman primate models and is discussed as a potential strategy for CTA. (C) 2000 Wiley-Liss, Inc. C1 USN, NIDDK, Navy Transplantat & Autoimmun Branch, Res Ctr, Bethesda, MD 20889 USA. RP Kirk, AD (reprint author), USN, NIDDK, Navy Transplantat & Autoimmun Branch, Res Ctr, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. RI Kirk, Allan/B-6905-2012 NR 37 TC 22 Z9 24 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0738-1085 J9 MICROSURG JI Microsurgery PY 2000 VL 20 IS 8 BP 430 EP 434 DI 10.1002/1098-2752(2000)20:8<430::AID-MICR14>3.0.CO;2-K PG 5 WC Surgery SC Surgery GA 389MV UT WOS:000166242900013 PM 11150995 ER PT J AU Alexander, GA Brawley, OW AF Alexander, GA Brawley, OW TI Association of Helicobacter pylori infection with gastric cancer SO MILITARY MEDICINE LA English DT Article ID DUODENAL-ULCER DISEASE; CAMPYLOBACTER-PYLORI; HIGH-RISK; ATROPHIC GASTRITIS; PATHOLOGICAL SEQUENCE; INTESTINAL METAPLASIA; ANTIBODY PREVALENCE; CARCINOMA; EPIDEMIOLOGY; SERUM AB Background: Helicobacter pylori has generated public health interest since its identification in 1983, Past studies have suggested that the bacterium plays a role in the pathogenesis of gastric cancer, More recent studies support the conclusion that the association of H, pylori with gastric cancer is causal, The purpose of this article is to review the available evidence supporting the association of H, pylori with gastric cancer. Methods: We performed a critical review of the relevant literature published in the English language on H. pylori and gastric cancer using MEDLINE, Index Medicus for the years 1985 to 1997, The reference lists of selected articles also were reviewed to capture citations for further pertinent studies. Results: H, pylori is thought to be the major cause of chronic atrophic gastritis. H. pylori gastritis is worldwide in distribution. H. pylori is now categorized by the International Agency for Cancer Research as a group 1 carcinogen, i.e., an agent that is carcinogenic to humans. Several reports from the United States have found the highest frequencies of gastric cancer in geographic areas and populations with the highest rates of acquisition of H. pylori infection. The high prevalence of Il. pylori infection has been documented most notably in blacks and Hispanics, who also are at high risk for gastric cancer, Conclusions: New studies that focus on the epidemiology and pathology of H. pylori improve our understanding of its relationship with gastric cancer and advance the development of gastric cancer prevention and control strategies that are proposed. C1 NCI, Off Special Populat Res, NIH, Bethesda, MD 20892 USA. RP Alexander, GA (reprint author), NCI, Off Special Populat Res, NIH, Execut Plaza S,Room 320, Bethesda, MD 20892 USA. NR 87 TC 17 Z9 23 U1 1 U2 2 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JAN PY 2000 VL 165 IS 1 BP 21 EP 28 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 276HE UT WOS:000084871300005 PM 10658423 ER PT J AU Srivastava, RK Srivastava, AR Cho-Chung, YS AF Srivastava, RK Srivastava, AR Cho-Chung, YS TI Synergistic effects of 8-Cl-cAMP and retinoic acids in the inhibition of growth and induction of apoptosis in ovarian cancer cells: Induction of retinoic acid receptor beta SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE retinoic acid; RAR beta; protein kinase A; apoptosis; caspase ID EXPRESSION; DIFFERENTIATION; ACTIVATION; PROTEIN; DEATH; PROLIFERATION; ELEMENT; LINE; GENE AB Both cAMP and retinoids play a role in cell differentiation and the control of cell growth. A site-selective cAMP analog, 8-Cl-cAMP and retinoic acid synergistically inhibit growth and induce apoptosis in certain cancer cells. In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective even at doses that are toxic to the host. The objective of our present study was to examine the mechanism(s) of synergistic effects of retinoic acid (9-cis, 13-cis or all-trans RA) and 8-Cl-cAMP on apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. RA induced growth inhibition and apoptosis in OVCAR-3 and OVCAR-8 cells. 8-Cl-cAMP acted synergistically with RA in inducing and activating retinoic acid receptor beta (RAR beta) which correlates with growth inhibition and apoptosis in both cell types. In addition, induction of apoptosis by RA plus 8-Cl-cAMP requires caspase-3 activation followed by cleavage of anti-poly(ADP-ribose) polymerase. Furthermore, mutations in CRE-related motif within the RAR beta promoter resulted in loss of both transcriptional activation of RAR beta and synergy between RA and 8-Cl-cAMP. RAR beta expression appears to be associated with induction of apoptosis. Introduction of the RAR beta gene into OVCAR-3 cells resulted in gain of RA sensitivity. Loss of RAR beta expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. Thus, combined treatment with RA and 8-Cl-cAMP may provide an effective means for inducing RAR beta expression leading to apoptosis in ovarian cancer cells. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, Bldg 10,Room 5B05, Bethesda, MD 20892 USA. NR 30 TC 15 Z9 19 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 2000 VL 204 IS 1-2 BP 1 EP 9 DI 10.1023/A:1007074814676 PG 9 WC Cell Biology SC Cell Biology GA 286TV UT WOS:000085463000001 PM 10718618 ER PT J AU Song, S Grenfell, TZ Garfield, S Erikson, RL Lee, KS AF Song, S Grenfell, TZ Garfield, S Erikson, RL Lee, KS TI Essential function of the polo box of Cdc5 in subcellular localization and induction of cytokinetic structures SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE CDC5; XENOPUS EGG EXTRACTS; KINESIN-LIKE PROTEIN; CELL-CYCLE CONTROL; ANIMAL-CELLS; SERINE/THREONINE KINASE; DROSOPHILA POLO; SEPTIN FUNCTION; BUDDING YEAST; GENE AB Members of the polo subfamily of protein kinases play pivotal roles in cell proliferation. In addition to the kinase domain, polo kinases have a strikingly conserved sequence in the noncatalytic C-terminal domain, termed the polo box. Here we show that the budding-yeast polo kinase Cdc5, when fused to green fluorescent protein and expressed under its endogenous promoter, localizes at spindle poles and the mother bud neck. Overexpression of Cdc5 can induce a class of cells with abnormally elongated buds in a polo box- and kinase activity-dependent manner. In addition to localizing at the spindle poles and cytokinetic neck filaments, Cdc5 induces and localizes to additional septin ring structures within the elongated buds. Without impairing kinase activity, conservative mutations in the polo box abolish the ability of Cdc5 to functionally complement the defect associated with a cdc5-1 temperature-sensitive mutation, to localize to the spindle poles and cytokinetic neck filaments, and to induce elongated cells with ectopic septin ring structures. Consistent with the polo box-dependent subcellular localization, the C-terminal domain of Cdc5, but not its polo box mutant, is sufficient for subcellular localization, and its overexpression appears to inhibit cytokinesis, These data provide evidence that the polo box is required to direct Cdc5 to specific subcellular locations and induce or organize cytokinetic structures. C1 NCI, Lab Metab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Lee, KS (reprint author), NCI, Lab Metab, Div Basic Sci, NIH, 9000 Rockville Pike,Bldg 37,Rm 3D25, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA42580] NR 50 TC 115 Z9 115 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2000 VL 20 IS 1 BP 286 EP 298 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 265DY UT WOS:000084227100029 PM 10594031 ER PT J AU Soldaini, E John, S Moro, S Bollenbacher, J Schindler, U Leonard, WJ AF Soldaini, E John, S Moro, S Bollenbacher, J Schindler, U Leonard, WJ TI DNA binding site selection of dimeric and tetrameric Stat5 proteins reveals a large repertoire of divergent tetrameric Stat5a binding sites SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-HORMONE; NUCLEIC-ACIDS; AMINO-ACID; GENE; SEQUENCE; TRANSCRIPTION; PROMOTER; CLONING; DOMAIN; INTERLEUKIN-3 AB We have defined the optimal binding sites for Stat5a and Stat5b homodimers and found that they share similar core TTC(T/C)N(G/A)GAA interferon gamma-activated sequence (GAS) motifs. Stat5a tetramers can bind to tandemly linked GAS motifs, but the binding site selection revealed that tetrameric binding also can be seen with a wide range of nonconsensus motifs, which in many cases did not allow Stat5a binding as a dimer. This indicates a greater degree of flexibility in the DNA sequences that allow binding of Stat5a tetramers than dimers. Indeed, in an oligonucleotide that could bind both dimers and tetramers, it was possible to design mutants that affected dimer binding without affecting tetramer binding. A spacing of 6 bp between the GAS sites was most frequently selected, demonstrating that this distance is favorable for Stat5a tetramer binding. These data provide insights into tetramer formation by Stat5a and indicate that the repertoire of potential binding sites for this transcription factor is broader than expected. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Tularik Inc, S San Francisco, CA 94080 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252, Bethesda, MD 20892 USA. RI Moro, Stefano/A-2979-2012 OI Moro, Stefano/0000-0002-7514-3802 NR 40 TC 119 Z9 125 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2000 VL 20 IS 1 BP 389 EP 401 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 265DY UT WOS:000084227100039 PM 10594041 ER PT J AU Herrera, JE West, KL Schiltz, RL Nakatani, Y Bustin, M AF Herrera, JE West, KL Schiltz, RL Nakatani, Y Bustin, M TI Histone H1 is a specific repressor of core histone acetylation in chromatin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; ACETYLTRANSFERASE ACTIVITY; TRANSCRIPTIONAL REGULATION; NUCLEOSOMAL ARRAYS; LINKER HISTONES; MMTV PROMOTER; ADA-COMPLEX; IN-VIVO; DNA; GENE AB Although a link between histone acetylation and transcription has been established, it is not clear how acetylases function in the nucleus of the cell and how they access their targets in a chromatin fiber containing H1 and folded into a highly condensed structure. Here we show that the histone acetyltransferase (HAT) p300/CBP-associated factor (PCAF), either alone or in a nuclear complex, can readily acetylate oligonucleosomal substrates. The linker histones, H1 and H5, specifically inhibit the acetylation of mono- and oligonucleosomes and not that of free histones or histone-DNA mixtures. We demonstrate that the inhibition is due mainly to steric hindrance of H3 by the tails of linker histones and not to condensation of the chromatin fiber. Cellular PCAF, which is complexed with accessory proteins in a multiprotein complex, can overcome the linker histone repression. We suggest that linker histones hinder access of PCAF, and perhaps other HATs, to their target acetylation sites and that perturbation of the linker histone organization in chromatin is a prerequisite for efficient acetylation of the histone tails in nucleosomes. C1 NCI, Prot Sect, Mol Carcinogenesis Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Herrera, JE (reprint author), NCI, Prot Sect, Mol Carcinogenesis Lab, Div Basic Sci,NIH, Bldg 37,Room 3D20, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 NR 60 TC 59 Z9 59 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2000 VL 20 IS 2 BP 523 EP 529 DI 10.1128/MCB.20.2.523-529.2000 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 270VZ UT WOS:000084559000011 PM 10611231 ER PT J AU Nishimura, S Takahashi, S Kuroha, T Suwabe, N Nagasawa, T Trainor, C Yamamoto, M AF Nishimura, S Takahashi, S Kuroha, T Suwabe, N Nagasawa, T Trainor, C Yamamoto, M TI A GATA box in the GATA-1 gene hematopoietic enhancer is a critical element in the network of GATA factors and sites that regulate this gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; MICE LACKING; EXPRESSION; CELLS; DIFFERENTIATION; PROMOTER; PROTEINS; GROWTH; DISRUPTION; LINEAGES AB A region located at kbp -3.9 to -2.6 5' to the first hematopoietic exon of the GATA-1 gene is necessary to recapitulate gene expression in both the primitive and definitive erythroid lineages. In transfection analyses, this region activated reporter gene expression from an artificial promoter in a position- and orientation-independent manner, indicating that the region functions as the GATA-1 gene hematopoietic enhancer (G1HE), However, when analyzed in transgenic embryos in viveo, G1HE activity was orientation dependent and also required the presence of the endogenous GATA-1 gene hematopoietic promoter. To define the boundaries of G1HE, a series of deletion constructs were prepared and tested in transfection and transgenic mice analyses, We show that G1HE contains a 149-bp core region which is critical for GATA-1 gene expression in both primitive and definitive erythroid cells but that expression in megakaryocytes requires the core plus additional sequences from G1HE. This core region contains one GATA, one GAT, and two E boxes. Mutational analyses revealed that only the GATA box is critical for gene-regulatory activity. Importantly, G1HE was active in SCL-/- embryos, These results thus demonstrate the presence of a critical network of GATA factors and GATA binding sites that controls the expression of this gene. C1 Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 3058577, Japan. Univ Tsukuba, Inst Basic Med Sci, Tsukuba, Ibaraki 3058577, Japan. Univ Tsukuba, Inst Clin Med, Tsukuba, Ibaraki 3058577, Japan. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yamamoto, M (reprint author), Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, 1-1-1 Tennoudai, Tsukuba, Ibaraki 3058577, Japan. RI Yamamoto, Masayuki/A-4873-2010 NR 36 TC 93 Z9 95 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2000 VL 20 IS 2 BP 713 EP 723 DI 10.1128/MCB.20.2.713-723.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 270VZ UT WOS:000084559000030 PM 10611250 ER PT J AU Chong, LD Park, EK Latimer, E Friesel, R Daar, IO AF Chong, LD Park, EK Latimer, E Friesel, R Daar, IO TI Fibroblast growth factor receptor-mediated rescue of x-ephrin B1-induced cell dissociation in Xenopus embryos SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NEURAL CREST MIGRATION; MOTOR AXON GUIDANCE; FGF RECEPTOR; TYROSINE KINASE; TRANSMEMBRANE LIGANDS; ADHESION MOLECULES; MESODERM INDUCTION; DROSOPHILA EMBRYO; NERVOUS-SYSTEM; MESSENGER-RNA AB The Eph family of receptor tyrosine kinases and their membrane-bound ligands, the ephrins, have been implicated in regulating cell adhesion and migration during development by mediating cell-to-cell signaling events. Genetic evidence suggests that ephrins may transduce signals and become tyrosine phosphorylated during embryogenesis. However, the induction and functional significance of ephrin phosphorylation is not yet clear. Here, we report that when we used ectopically expressed proteins, we found that an activated fibroblast growth factor (FGF) receptor associated with and induced the phosphorylation of ephrin B1 on tyrosine. Moreover, this phosphorylation reduced the ability of overexpressed ephrin B1 to reduce cell adhesion. In addition, we identified a region in the cytoplasmic tail of ephrin B1 that is critical for interaction with the FGF receptor; we also report FGF-induced phosphorylation of ephrins in a neural tissue. This is the first demonstration of communication between the FGF receptor family and the Eph ligand family and implicates cross talk between these two cell surface molecules in regulating cell adhesion. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Maine Med Ctr, Res Inst, Ctr Mol Med, Portland, ME 04106 USA. RP Daar, IO (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Bldg 567,Room 228, Frederick, MD 21702 USA. OI Daar, Ira/0000-0003-2657-526X FU NCI NIH HHS [N01-CO-5600]; NIDCR NIH HHS [DE 13248, R01 DE013248] NR 80 TC 69 Z9 72 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 2000 VL 20 IS 2 BP 724 EP 734 DI 10.1128/MCB.20.2.724-734.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 270VZ UT WOS:000084559000031 PM 10611251 ER PT S AU Nehlin, JO Skovgaard, GL Bohr, VA AF Nehlin, JO Skovgaard, GL Bohr, VA BE Toussaint, O Osiewacz, HD Lithgow, GJ Brack, C TI The Werner syndrome - A model for the study of human aging SO MOLECULAR AND CELLULAR GERONTOLOGY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT EMBO Workshop on Molecular and Cellular Gerontology CY SEP 18-22, 1999 CL SERPIANO, SWITZERLAND SP European Molec Biol Org, AETAS, Biogerontology, Kluwer Acad Publishers, Clontech AG, Crossair Ltd Co Reg European Air Transport, F Hoffmann La Roche AG, Freiwillege Akad Gesell, Geriatr Univ Clin, Novartis Pharma AG, Psychiat Univ Clin, Res Into Aging, London, Swiss Acad Med Sci, Verum, Fdn Behav & Environm ID REPLICATION PROTEIN-A; SINGLE-STRANDED-DNA; SYNDROME GENE-PRODUCT; NUCLEOTIDE EXCISION-REPAIR; LYMPHOBLASTOID CELL-LINES; S-PHASE; HELICASE GENE; RECQ FAMILY; IN-VIVO; NUCLEAR-LOCALIZATION AB Human aging is a complex process that leads to the gradual deterioration of body functions with time. Various models to approach the study of aging have been launched over the years such as the genetic analysis of life span in the yeast S. cerevisiae, the worm C. elegans, the fruitfly, and mouse, among others. In human models, there have been extensive efforts using replicative senescence, the study of centenerians, comparisons of young versus old at the organismal, cellular, and molecular levels, and the study of premature aging syndromes to understand the mechanisms leading to aging. One good model for studying human aging is a rare autosomal recessive disorder known as the Werner syndrome (WS), which is characterized by accelerated aging in vivo and in vitro. A genetic defect implicated in WS was mapped to the WRY locus. Mutations in this gene are believed to be associated, early in adulthood, with clinical symptoms normally found in old individuals. WRN functions as a DNA helicase, and recent evidence, summarized in this review, suggests specific biochemical roles for this multifaceted protein. The interaction of WRN protein with RPA (replication protein A) and p53 will undoubtedly direct efforts to further dissect the genetic pathway(s) in which WRN protein functions in DNA metabolism and mill help to unravel its contribution to the human aging profess. C1 Univ Copenhagen Hosp, Lab Mol Gerontol & Dermatol, DK-2100 Copenhagen, Denmark. NIA, Gerontol Res Ctr, Mol Genet Lab, Baltimore, MD 21224 USA. RP Nehlin, JO (reprint author), Univ Copenhagen Hosp, Lab Mol Gerontol & Dermatol, Blegdamsvej 9,Sect 6311, DK-2100 Copenhagen, Denmark. NR 105 TC 35 Z9 37 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-271-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 908 BP 167 EP 179 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Geriatrics & Gerontology SC Biochemistry & Molecular Biology; Cell Biology; Geriatrics & Gerontology GA BQ53H UT WOS:000088671200016 PM 10911957 ER PT J AU Deyev, SM Yazynin, SA Hartley, RW AF Deyev, SM Yazynin, SA Hartley, RW TI Modified ribonuclease gene ensures efficient positive selection in molecular cloning SO MOLECULAR BIOLOGY LA English DT Article DE molecular cloning; ribonuclease; polylinker ID PLASMID VECTOR; FRAGMENTS; BARNASE AB A novel strategy is proposed for positive selection of recombinant plasmids, based on the use of a conditionally lethal gene. Expression in Escherichia coli of the gene for a bacterial ribonuclease, barnase, kills the host cell. Incorporation of foreign DNA into the barnase gene results in synthesis of a defective catalytically inactive protein that does not affect the cell viability. Thus, colonies are formed only by the cells that carry plasmids with cloned DNA inserts, whereas any "background" that can arise from cells that have acquired the vector not cleaved by the restriction enzyme or with the ribonuclease gene restored by ligation or other events is obviated because such cells die. This approach was implemented using plasmids that carried the native barnase gene as well as variants with in-frame recognition sites for commonly used restriction enzymes. Computer modeling of the spatial structure of the corresponding barnase derivatives enabled prediction of their catalytic properties in order to choose the optimal version. The pMT440 vector construct contained the entire pUC19 polylinker instead of the Val36 codon of the barnase gene. The cytotoxity of barnase was not affected by this 19-aa insert, which validated our structural-functional premises. C1 Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. NIDNDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Deyev, SM (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. RI Deyev, Sergey/F-8191-2014 OI Deyev, Sergey/0000-0002-3952-0631 NR 15 TC 0 Z9 0 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU, 233 SPRING ST, NEW YORK, NY 10013 USA SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD JAN-FEB PY 2000 VL 34 IS 1 BP 39 EP 44 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 294JY UT WOS:000085909200008 ER PT B AU Klein, HG AF Klein, HG BE Sibinga, CTS Klein, HG TI Molecular biology in blood transfusion - Introduction SO MOLECULAR BIOLOGY IN BLOOD TRANSFUSION SE DEVELOPMENTS IN HEMATOLOGY AND IMMUNOLOGY LA English DT Proceedings Paper CT 24th International Symposium on Blood Transfusion CY 1999 CL GRONINGEN, NETHERLANDS SP Blood Bank Noord Nederland ID POLYMERASE CHAIN-REACTION; GENE-THERAPY; SEQUENCES C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-6534-8 J9 DEV HEMATOL PY 2000 VL 35 BP 3 EP 12 PG 10 WC Biochemistry & Molecular Biology; Hematology SC Biochemistry & Molecular Biology; Hematology GA BR72N UT WOS:000167335500001 ER PT J AU Lewis, MJ Nichols, BJ Prescianotto-Baschong, C Riezman, H Pelham, HRB AF Lewis, MJ Nichols, BJ Prescianotto-Baschong, C Riezman, H Pelham, HRB TI Specific retrieval of the exocytic SNARE Snc1p from early yeast endosomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SYNTAXIN HOMOLOG; ENDOPLASMIC-RETICULUM; ENDOCYTIC PATHWAY; SECRETORY PATHWAY; LATE-GOLGI; ALKALINE-PHOSPHATASE; TRANSMEMBRANE DOMAIN; MEMBRANE-PROTEINS; VACUOLAR MEMBRANE AB Many endocytosed proteins in yeast travel to the vacuole, but some are recycled to the plasma membrane. We have investigated the recycling of chimeras containing green fluorescent protein (GFP) and the exocytic SNARE Snc1p. GFP-Snc1p moves from the cell surface to internal structures when Golgi function or exocytosis is blocked, suggesting continuous recycling via the Golgi. Internalization is mediated by a conserved cytoplasmic signal, whereas diversion from the vacuolar pathway requires sequences within and adjacent to the transmembrane domain. Delivery from the Golgi to the surface is also influenced by the transmembrane domain, but the requirements are much less specific. Recycling requires the syntaxins Tlg1p and Tlg2p but not Pep12p or proteins such as Vps4p and Vps5p that have been implicated in late endosome-Golgi traffic. Subtle changes to the recycling signal cause GFP-Snc1p to accumulate preferentially in punctate internal structures, although it continues to recycle to the surface. The internal GFP-Snc1p colocalizes with Tlg1p, and immunofluorescence and immunoelectron microscopy reveal structures that contain Tlg1p, Tlg2p, and Kex2p but lack Pep12p and Sec7p. We propose that these represent early endosomes in which sorting of Snc1p and late Golgi proteins occurs, and that transport can occur directly from them to the Golgi apparatus. C1 MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Univ Basel, Biozentrum, CH-4056 Basel, Switzerland. RP Pelham, HRB (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Riezman, Howard/0000-0003-4680-9422 NR 60 TC 227 Z9 231 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 2000 VL 11 IS 1 BP 23 EP 38 PG 16 WC Cell Biology SC Cell Biology GA 278YJ UT WOS:000085016300004 PM 10637288 ER PT J AU Appukuttan, B Sood, R Ott, S Makalowska, I Patel, RJ Wang, XG Robbins, CM Brownstein, MJ Stout, JT AF Appukuttan, B Sood, R Ott, S Makalowska, I Patel, RJ Wang, XG Robbins, CM Brownstein, MJ Stout, JT TI Isolation and characterization of the human homeobox gene HOX D1 SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE development; exon; homeodomain; intron; labial ID DUANES RETRACTION SYNDROME; EMBRYONAL CARCINOMA-CELLS; RETINOIC ACID; EXPRESSION; ORGANIZATION; MURINE; FAMILY; NERVE; LOCI AB Homeobox genes, first identified in Drosophila, encode transcription factors that regulate embryonic development along the anteroposterior axis of an organism. Vertebrate homeobox genes are described on the basis of their homology to the genes found within the Drosophila Antennapedia and Bithorax homeotic gene complexes. Mammals possess four paralogous homeobox (HOX) gene clusters, HOX A, HOX B, HOX C and HOX D, each located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. We report the characterization of the human HOX D1 gene. This gene consists of two exons, encoding a 328 amino acid protein, separated by an intron of 354 bp. The human HOX D1 protein is one amino acid longer (328 amino acids) than the mouse protein (327 amino acids) and is 82% identical to the mouse HOX D1 homolog. The DNA binding homeodomain region of the human protein exhibits a 97% and 80% identity between mouse Hoxd1 and Drosophila labial homeodomains, respectively. The exon/intron and intron/exon splice junctions are conserved in position between human and mouse genes. Determination of the human HOX D1 gene structure permits the use of PCR based analysis of this gene for the assessment of mutations, for diseases that link to the HOXD cluster (such as Duanes Retraction Syndrome (DRS)), or polymorphisms associated with human variation. Molecular characterization of the HOXD1 gene may also permit analysis of the functional role of this gene in human neurogenisis. C1 Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Div Ophthalmol, Los Angeles, CA 90027 USA. NHGRI, NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Stout, JT (reprint author), Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. RI Brownstein, Michael/B-8609-2009 NR 27 TC 2 Z9 3 U1 0 U2 2 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. PY 2000 VL 27 IS 4 BP 195 EP 201 DI 10.1023/A:1011048931477 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439QT UT WOS:000169129100001 PM 11455954 ER PT J AU McCall, MJ Hendry, P Mir, AA Conaty, J Brown, G Lockett, TJ AF McCall, MJ Hendry, P Mir, AA Conaty, J Brown, G Lockett, TJ TI Small, efficient hammerhead ribozymes SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE ribozyme; hammerhead; miniribozyme; minizyme; ribozyme design ID NUCLEASE-RESISTANT RIBOZYMES; MESSENGER-RNA LEVELS; STEM-LOOP-II; IN-VITRO; OLIGONUCLEOTIDE FACILITATORS; CATALYTIC ACTIVITY; MEDIATED CLEAVAGE; ALPHA RIBOZYME; SELF-CLEAVAGE; SITES AB The hammerhead ribozyme is able to cleave RNA in a sequence-specific manner. These ribozymes are usually designed with four basepairs in helix II, and with equal numbers of nucleotides in the 5' and 3' hybridizing arms that bind the RNA substrate on either side of the cleavage site. Here guidelines are given for redesigning the ribozyme so that it is small, but retains efficient cleavage activity. First, the ribozyme may be reduced in size by shortening the 5' arm of the ribozyme to five or six nucleotides; for these ribozymes, cleavage of short substrates is maximal. Second: the internal double-helix of the ribozyme (helix II) may be shortened to one or no basepairs, forming a miniribozyme or minizyme, respectively. The sequence of the shortened helix + loop II greatly affects cleavage rates. With eight or more nucleotides in both the 5' and the 3' arms of a miniribozyme containing an optimized sequence for helix + loop II, cleavage rates of short substrates are greater than for analogous ribozymes possessing a longer helix II. Cleavage of gene-length RNA substrates may be best achieved by miniribozymes. C1 CSIRO Mol Sci, N Ryde, NSW 1670, Australia. NCI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. RI Hendry, Philip/D-5795-2011; McCall, Maxine/H-4707-2013; Lockett, Trevor/H-8970-2013 OI McCall, Maxine/0000-0003-4000-8069; Lockett, Trevor/0000-0002-8063-071X NR 53 TC 9 Z9 10 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD JAN PY 2000 VL 14 IS 1 BP 5 EP 17 DI 10.1385/MB:14:1:5 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 306BL UT WOS:000086576200002 PM 10911611 ER PT J AU Nebert, D Tennant, R Walker, C AF Nebert, D Tennant, R Walker, C TI Twelfth International Conference on Carcinogenesis and Risk Assessment Gene Environment Interactions: Emerging Issues, Technologies, and Biological Paradigms SO MOLECULAR CARCINOGENESIS LA English DT Editorial Material C1 Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Texas, MD Anderson Canc Ctr, Div Res, Smithville, TX 78957 USA. RP Nebert, D (reprint author), Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2000 VL 27 IS 1 BP 1 EP 1 DI 10.1002/(SICI)1098-2744(200001)27:1<1::AID-MC1>3.0.CO;2-# PG 1 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 280LA UT WOS:000085103200001 ER PT J AU Moysich, KB Freudenheim, JL Baker, JA Ambrosone, CB Bowman, ED Schisterman, EF Vena, JE Shields, PG AF Moysich, KB Freudenheim, JL Baker, JA Ambrosone, CB Bowman, ED Schisterman, EF Vena, JE Shields, PG TI Apolipoprotein E genetic polymorphism, serum lipoproteins, and breast cancer risk SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 12th International Conference on Carcinogenesis and Risk Assessment CY DEC 02-05, 1998 CL AUSTIN, TEXAS DE breast neoplasms; molecular epidemiology; apolipoprotein E allelic frequency; dietary fat; serum lipoproteins ID PLASMA-LIPIDS; DIETARY-FAT; NUTRITIONAL EPIDEMIOLOGY; INSULIN-RESISTANCE; CIGARETTE-SMOKING; E PHENOTYPE; FOLLOW-UP; CHOLESTEROL; WOMEN; TRIGLYCERIDE AB Apolipoprotein E (apoE) is a polymorphic gene involved in lipid metabolism with three common variant alleles (epsilon 2, epsilon 3 and epsilon 4). The epsilon 4 allele has been associated with elevated levels of cholesterol as well as greater risk of coronary heart disease and Alzheimer's disease. In this case-control study we examined whether apoE genotype affected the association between serum lipids and breast cancer risk. In a subset of a study in western New York, 260 women with incident, primary breast cancer and 332 community controls were interviewed and provided blood samples. Polymerase chain reaction-restriction fragment length polymorphism analyses of the apoE polymorphism were performed. Participants were classified as apoE2 (epsilon 2, epsilon 2 or epsilon 2, epsilon 3), apoE2 (epsilon 3, epsilon 3), or apoE4 (epsilon 4, epsilon 4 or epsilon 4, epsilon 3). no unconditional logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CI). Compared with women with the apoE3 genotype, there were no association with the risk for women with the apoE2 (OR = 1.0; 95% CI = 0.91 - 1.64) or apoE4 genotype (OR = 0.97; 95% CI = 0.63 - 1.54). higher serum levels of total cholesterol, HDL cholesterol, and LDL cholesterol were not associated with risk, either in the total sample or among subgroups of women defined by the apoE genotype. Women with the highest serum triglyceride levels had an increase in risk (OR = 1.63; 95% CI = 1.03 - 2.59) compared to women with the lowest levels. This effect was not apparent among women with the apoE2 or apoE3 genotype, but much stronger among women with the apoE4 genotype (OR = 4.69; 95% CI = 1.49 - 14.7). These data suggest that the apoE4 genotype may modify the association between serum triglycerides and brest cancer risk. (C) 2000 Wiley-Liss, Inc. C1 Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Buffalo, NY 14263 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NCI, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Moysich, KB (reprint author), Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Elm & Carlton St, Buffalo, NY 14263 USA. RI Shields, Peter/I-1644-2012; OI Schisterman, Enrique/0000-0003-3757-641X NR 56 TC 37 Z9 40 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2000 VL 27 IS 1 BP 2 EP 9 DI 10.1002/(SICI)1098-2744(200001)27:1<2::AID-MC2>3.0.CO;2-W PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 280LA UT WOS:000085103200002 PM 10642431 ER PT J AU Dunn, SE Torres, JC Nihei, N Barrett, JC AF Dunn, SE Torres, JC Nihei, N Barrett, JC TI The insulin-like growth factor-1 elevates urokinase-type plasminogen activator-1 in human breast cancer cells: A new avenue for breast cancer therapy SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 12th International Conference on Carcinogenesis and Risk Assessment CY DEC 02-05, 1998 CL AUSTIN, TEXAS DE breast cancer; insulin-like growth factor-1; metastasis; urokinase-type plasminogen activator-1 ID FACTOR-I RECEPTOR; METASTASIS; INVASION; TAMOXIFEN; MICE; INVASIVENESS; ANGIOGENESIS; EXPRESSION; PREVENTION; INHIBITOR AB Tumor recurrence is a common problem in the treatment of breast cancer. In breast cancer, the expression of high protein levels of the insulin-like growth factor-1 receptor (IGF-1R) and urokinase-type plasminogen activator-1 (uPA) is strongly associated with breast cancer recurrence and decreased survival. The expression of uPA by tumors is thought to not only stimulate tumor invasion but also facilitate angiogenesis. In this study, our goal was to address whether IGF-1R could influence the expression of the extracellular matrix proteases, matrix metalloproteinase (MMP), or uPA thus allowing a selective advantage for tumor invasion and concomitant neovascularization. Initially, we determined whether or not insulin-like growth factor (IGF)-1 regulated the production MMP or uPA in the human breast cancer MDA-MB-231 cells. There was no increase in MMP activity when the cells were treated with IGF-1 (10 ng/mL) for 24 h. In contrast, uPA mRNA and protein were induced in a time-dependent manner. Furthermore, clones expression a dominant negative inhibitor of IGF-1R termed 486stop had less uPA mRNA, and the clones were less invasive through Matrigel. Taken together, these data illustrate that IGF-1R stimulates uPA production. Hence, these two prognostic indicators may be interrelated, suggesting they may function in a synergistic manner to facilitate local tumor invasion as well as angiogenesis. Our data suggest that disruption of IGF-1 signaling in breast cancer may lead to breast cancer prevention and intervention by decreasing uPA expression. (C) 2000 Wiley-Liss, Inc. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Barrett, JC (reprint author), NIEHS, NIH, 111 TW Alexander Dr,Mail Drop AZ-01, Res Triangle Pk, NC 27709 USA. NR 33 TC 39 Z9 39 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2000 VL 27 IS 1 BP 10 EP 17 DI 10.1002/(SICI)1098-2744(200001)27:1<10::AID-MC3>3.0.CO;2-Z PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 280LA UT WOS:000085103200003 PM 10642432 ER PT J AU Blazer, DG Umbach, DM Bostick, RM Taylor, JA AF Blazer, DG Umbach, DM Bostick, RM Taylor, JA TI Vitamin D receptor polymorphisms and prostate cancer SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 12th International Conference on Carcinogenesis and Risk Assessment CY DEC 02-05, 1998 CL AUSTIN, TEXAS DE vitamin D receptor; prostate cancer; polymorphism; epidemiology; vitamin D ID CELL-LINES; D METABOLITES; GENE POLYMORPHISMS; UNITED-STATES; MESSENGER-RNA; ASSOCIATION; ALLELES; INHIBITION; EXPRESSION; GROWTH AB Prostate can be a common disease, yet determinants of prostate cancer risk remain largely unidentified. Low circulating levels of 1,23-dihydroxy vitamin D (1,25-D) have been implicated as a risk factor for prostate cancer. In addition, 1,25-D exhibits significant antineoplastic properties both in vitro and in vivo, and these antiproliferative effects appear to be mediated through the vitamin D receptor (VDR). The VDR has a number of common polymorhisms, including a TaqI restriction fragment length polymorphism in exon 9 and a poly(A) length polymorphism in the 3'-untranslated region. Previous studies have found an association between the TaqI T allele or poly(A) L allele and prostate cancer. To further investigate the putative link between VDR polymorphisms and prostate cancer, we conducted a case-control study of prostate cancer patients from the Piedmont region of North Carolina. Using polymerase chain reaction-based techniques on DNA extracted from peripheral blood, we genotyped 77 cases (70 white, seven black) and 183 controls (169 white, 14 black) for the TaqI and poly(A) alleles. We report here an overall lack of association between either the TaqI or poly(A) genotype and prostate cancer odds ratio (OR) = 1.4, 95% confidence interval (Cl) = 0.7-2.8; and OR = 1.2, 95% Cl = 0.6-2.5, respectively). Using a case-case analysis, we tested whether these polymorphisms wight be associated with more advanced disease but found no statistically significant association for the TaqI or poly(A) L allele (OR = 2.5, 95% Cl = 0.3-2.17; OR = 2.8, 95% Cl = 0.3-23.8, respectively). We report strong evidence of linkage disequilibrium between the TaqI and poly(A) polymorphisms (P < 0.0001), with whites demonstrating stronger linkage disequilibrium than blacks (D = =0.24 vs. D = 0.18). (C) Wiley-Liss, Inc. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Wake Forest Univ, Bowman Gray Sch Med, Mol Carcinogenesis Lab, Winston Salem, NC USA. Wake Forest Univ, Bowman Gray Sch Med, Biostat Branch, Winston Salem, NC USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci Epidemiol, Winston Salem, NC USA. RP Taylor, JA (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. RI Blazer, Dan/F-7659-2015; OI Blazer, Dan/0000-0002-7261-9254; taylor, jack/0000-0001-5303-6398 NR 35 TC 70 Z9 70 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2000 VL 27 IS 1 BP 18 EP 23 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 280LA UT WOS:000085103200004 PM 10642433 ER PT J AU Trempus, CS Bishop, WR Njoroge, FG Boll, RJ Battalora, MS Mahler, JG Haseman, JK Tennant, RW AF Trempus, CS Bishop, WR Njoroge, FG Boll, RJ Battalora, MS Mahler, JG Haseman, JK Tennant, RW TI A farnesyl transferase inhibitor suppresses TPA-mediated skin tumor development without altering hyperplasia in the ras transgenic Tg.AC mouse SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 12th International Conference on Carcinogenesis and Risk Assessment CY DEC 02-05, 1998 CL AUSTIN, TEXAS DE phorbol ester; farnesylation; skin tumorigenesis ID FARNESYLTRANSFERASE INHIBITORS; PROTEIN TRANSFERASE; PAPILLOMA DEVELOPMENT; MICE; CARCINOGENESIS; TUMORIGENESIS; ASSOCIATION; REGRESSION; EXPRESSION; MUTATIONS AB The Tg.AC mouse carries an activated v-Ha-ras oncogene fused to an embryonic zeta-globin promoter and develops cutaneous papillomas in response to specific chemicals, full thickness wounding, and ultraviolet radiation. Papilloma development in these mice has been suggested to be dependent upon activation of ras transgene expression, thus providing a potential model for studying ras-inhibitory componds. Farnesyl transferase inhibitors (FTIs) prevent a critical posttranslational modification step necessary for activation of ras proteins. Our studies demonstrated that a tricyclic FTI (SCH 56582) applied directly to the skin of homozygous Tg.AC mice 1 h prior to administration of the tumor promoter TPA decreased tumor multiplicity compared to TPA-only controls. In addition, a reduction of TPA-induced tumor development was seen in similarly treated hemizygous Tg.AC mice either on an FVB/N strain background or 50% C57BL/6. Histological examination of skin from Tg.AC(+/-) FVB/N mice revealed no differences with respect to 12-O-tetradecamoylpharbol-13-acetate (TPA)-mediated hyperplasia. Keratinocytes isolated from treated and control skin were assayed for ras transgene expression by reverse transcription-polymerase chain reaction, and expression was detected in both TPA- and FTI + TPA-treated tissue, although the appearance of transgene positive pre-papillomas was observed only in histological sections taken 21 d after the first treatment. In summary, we have used a regimen of topical application of an FTI (SCH 56582) to suppress TPA-mediated papillomagenesis in v-Ha-ras transgenic Tg.AC mice. These studies demonstrate that TPA-induced epidermal hyperplasia is a ras-independent process, while papilloma development in response to TPA treatment requires the function of activated ras. (C) 2000 Wiley-Liss, Inc. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Trempus, CS (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. NR 33 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2000 VL 27 IS 1 BP 24 EP 33 DI 10.1002/(SICI)1098-2744(200001)27:1<24::AID-MC5>3.0.CO;2-M PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 280LA UT WOS:000085103200005 PM 10642434 ER PT J AU Kunz, J Wilson, MP Kisseleva, M Hurley, JH Majerus, PW Anderson, RA AF Kunz, J Wilson, MP Kisseleva, M Hurley, JH Majerus, PW Anderson, RA TI The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity SO MOLECULAR CELL LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; PROTEIN-KINASE; 4-PHOSPHATE 5-KINASE; PLASMA-MEMBRANE; FACTOR RECEPTOR; HUMAN PLATELETS; PH DOMAIN; IN-VIVO; PHOSPHORYLATION; BINDING AB Phosphatidylinositol-4,5-bisphosphate plays a pivotal role in the regulation of cell proliferation and survival, cytoskeletal reorganization, and membrane trafficking. However, little is known about the temporal and spatial regulation of its synthesis. Higher eukaryotic cells have the potential to use two distinct pathways for the generation of phosphatidylinositol-4,5-bisphosphate. These pathways require two classes of phosphatidylinositol phosphate kinases, termed type I and type II PIP kinases. While highly related by sequence, these kinases localize to different subcellular compartments, phosphorylate distinct substrates, and are functionally nonredundant Here, we show that a 20- to 25-amino acid loop spanning the catalytic site, termed the activation loop, determines both enzymatic specificity and subcellular targeting of PIP kinases. Therefore, the activation loop controls signaling specificity and PIP kinase function at multiple levels. C1 Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. Washington Univ, Sch Med, Dept Internal Med, Div Hematol Oncol, St Louis, MO 63100 USA. Washington Univ, Sch Med, Dept Biol Chem, Div Hematol Oncol, St Louis, MO 63100 USA. Washington Univ, Sch Med, Dept Mol Biophys, Div Hematol Oncol, St Louis, MO 63100 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Anderson, RA (reprint author), Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. OI Anderson, Richard/0000-0001-6265-8359 NR 55 TC 102 Z9 103 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JAN PY 2000 VL 5 IS 1 BP 1 EP 11 DI 10.1016/S1097-2765(00)80398-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 281MB UT WOS:000085163400001 PM 10678164 ER PT J AU Kirshner, S Palmer, L Bodor, J Saji, M Kohn, LD Singer, DS AF Kirshner, S Palmer, L Bodor, J Saji, M Kohn, LD Singer, DS TI Major histocompatibility class I gene transcription in thyrocytes: A series of interacting regulatory DNA sequence elements mediate thyrotropin/cyclic adenosine 3 ',5 '-monophosphate repression SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NF-KAPPA-B; CAMP RESPONSE ELEMENT; RECEPTOR PROMOTER; THYROID-CELLS; TSH RECEPTOR; CREM GENE; EXPRESSION; BINDING; COMPLEX; PROTEIN AB in response to TSH, thyroid cells decrease major histocompatibility (MHC) class I expression and transcription, providing an excellent model for studying the dynamic modulation of transcription of MHC class I genes. Here we show that protein kinase A (PKA), a downstream effector of the TSH/cAMP pathway, reproduces the effects of TSH in repressing class I transcription. PKA/cAMP-mediated repression of transcription involves multiple interacting upstream response elements in the class I promoter: an element extending from -127 to -90 bp containing a CRE-like core, and at least two elements within an upstream 30-bp segment (-160 to -130 bp), which overlaps with the interferon regulatory element. ICER (inducible cAMP early response), a transcriptional repressor induced by TSH/cAMP can decrease class I promoter activity when introduced into FRTL-5 thyroid cells in the absence of TSH/cAMP. ICER binds to both the CRE-like element and the upstream 30-bp segment, generating a novel TSH-induced ternary complex. The present studies led to the proposal that TSH-mediated repression of class I transcription is the result of integrating signals from transcription factors through the higher order interactions of multiple regulatory elements. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B-36, Bethesda, MD 20892 USA. EM Dinah.Singer@nih.gov RI Saji, Motoyasu/E-4007-2011 NR 39 TC 13 Z9 13 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 JAN PY 2000 VL 14 IS 1 BP 82 EP 98 DI 10.1210/me.14.1.82 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 269NX UT WOS:000084485400008 PM 10628749 ER PT J AU Imada, K Leonard, WJ AF Imada, K Leonard, WJ TI The Jak-STAT pathway SO MOLECULAR IMMUNOLOGY LA English DT Review ID RECEPTOR-GAMMA-CHAIN; SEVERE COMBINED IMMUNODEFICIENCY; PROTEIN-TYROSINE KINASE; DEFECTIVE LYMPHOID DEVELOPMENT; COLONY-STIMULATING FACTOR; PERIPHERAL-BLOOD CELLS; DNA-BINDING ACTIVITY; MICE LACKING JAK3; SIGNAL-TRANSDUCTION; GENE-EXPRESSION AB A variety of important cellular functions are regulated by cytokines, The Jak-STAT pathway is one of the important signaling pathways downstream of cytokine receptors, Following binding of a ligand to its cognate receptor, receptor-associated Jaks are activated. STAT proteins are then in turn activated by tyrosine phosphorylation by Jak kinases, allowing their dimerization and subsequent translocation into the nucleus, where they modulate expression of target genes. Indispensable functions of Jaks and STATs in cytokine signaling in vivo have been revealed through knockout mouse studies, Moreover, the recent discovery of the CIS/SOCS/JAB/SSI family of inhibitors has contributed to understanding how this pathway is negatively regulated. Published by Elsevier Science Ltd. C1 NHLBI, Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Mol Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 127 TC 354 Z9 383 U1 2 U2 31 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 JAN-FEB PY 2000 VL 37 IS 1-2 BP 1 EP 11 DI 10.1016/S0161-5890(00)00018-3 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 318MP UT WOS:000087288200001 PM 10781830 ER PT J AU Johnson, AC Murphy, BA Matelis, CM Rubinstein, Y Piebenga, EC Akers, LM Neta, G Vinson, C Birrer, M AF Johnson, AC Murphy, BA Matelis, CM Rubinstein, Y Piebenga, EC Akers, LM Neta, G Vinson, C Birrer, M TI Activator protein-1 mediates induced but not basal epidermal growth factor receptor gene expression SO MOLECULAR MEDICINE LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; BREAST-CANCER CELLS; DNA-BINDING PROTEIN; EGF-RECEPTOR; TRANSCRIPTION FACTOR; T(15-17) TRANSLOCATION; MOLECULAR-CLONING; HUMAN P53; PROMOTER; ONCOGENE AB Background: The epidermal growth factor receptor (EGFR) is expressed at different levels in many cell types and found overexpressed in many cancers. EGFR expression is increased or decreased in response to extracellular stimuli. We examined the effect of increased c-Jun expression on EGFR promoter activity. Materials and Methods: We used DNAse I footprinting analysis to determine the binding of activator protein 1 (AP-1) to the promoter region. We also used cotransfection experiments and western blotting analysis to determine the effect of AP-1 family members on EGFR expression. Results: AP-1 was able to bind to at least seven sites in the EGFR promoter region. Cotransfection of MCF-7 cells with a c-Jun expression vector and the EGFR promoter reporter resulted in a 7-fold increase in promoter activity. JunB, but not c-fos, also enhanced the EGFR promoter activity. An A-Fos-dominant negative shown to inhibit Jun-dependent transactivation was able to prevent c-Jun induction of the promoter activity, but only slightly decreased the basal activity of the promoter. Furthermore, the A-Fos dominant negative was able to inhibit phorbol ester induction of the EGFR promoter. Examination of EGFR expression of MCF-7 stable cell lines that overexpress c-Jun revealed an increase in EGFR expression. Additionally, a cisplatin-resistant cell line, A2780/CP70, which has an increase in AP-1 activity compared with the parental cell line, A2780, was found to have an increase in EGFR level. Conclusions: These results indicate that AP-1 can act to increase the expression of EGFR and may play a role in upregulation of EGFR in cancer cells. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Biomarkers & Prevent Res Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37 Room 2D18,37 Convent Dr MSC-4255, Bethesda, MD 20892 USA. EM aj2e@nih.gov NR 59 TC 54 Z9 61 U1 0 U2 1 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PD JAN PY 2000 VL 6 IS 1 BP 17 EP 27 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 304CJ UT WOS:000086464800002 PM 10803405 ER PT J AU Hayward, RE DeRisi, JL Alfadhli, S Kaslow, DC Brown, PO Rathod, PK AF Hayward, RE DeRisi, JL Alfadhli, S Kaslow, DC Brown, PO Rathod, PK TI Shotgun DNA microarrays and stage-specific gene expression in Plasmodium falciparum malaria SO MOLECULAR MICROBIOLOGY LA English DT Article ID TRANSMISSION-BLOCKING ANTIBODIES; DRUG-RESISTANCE; CLONING; PROTEIN; ANTIGENS; TARGET AB Malaria infects over 200 million individuals and kills 2 million young children every year. Understanding the biology of malarial parasites will be facilitated by DNA microarray technology, which can track global changes in gene expression under different physiological conditions. However, genomes of Plasmodium sp. (and many other important pathogenic organisms) remain to be fully sequenced so, currently, it is not possible to construct gene-specific microarrays representing complete malarial genomes. In this study, 3648 random inserts from a Plasmodium falciparum mung bean nuclease genomic library were used to construct a shotgun DNA microarray. Through differential hybridization and sequencing of relevant clones, large differences in gene expression were identified between the blood stage trophozoite form of the malarial parasite and the sexual stage gametocyte form. The present study lengthens our list of stage-specific transcripts in malaria by at least an order of magnitude above all previous studies combined. The results offer an unprecedented number of leads for developing transmission blocking agents and for developing vaccines directed at blood stage antigens. A significant fraction of the stage-selective transcripts had no sequence homologues in the current genome data bases, thereby underscoring the importance of the shotgun approach. The malarial shotgun microarray will be useful for unravelling additional important aspects of malaria biology and the general approach may be applied to any organism, regardless of how much of its genome is sequenced. C1 Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Biochem, Stanford, CA 94305 USA. RP Rathod, PK (reprint author), Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. FU NIAID NIH HHS [AI26912, AI40956] NR 30 TC 173 Z9 179 U1 0 U2 8 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2000 VL 35 IS 1 BP 6 EP 14 DI 10.1046/j.1365-2958.2000.01730.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 276GJ UT WOS:000084867000002 PM 10632873 ER PT J AU Masereeuw, R Terlouw, SA van Aubel, RAMH Russel, FGM Miller, DS AF Masereeuw, R Terlouw, SA van Aubel, RAMH Russel, FGM Miller, DS TI Endothelin B receptor-mediated regulation of ATP-driven drug secretion in renal proximal tubule SO MOLECULAR PHARMACOLOGY LA English DT Article ID ORGANIC ANION TRANSPORTER; NONIONIC CONTRAST-MEDIA; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; MESSENGER-RNA; RAT-KIDNEY; LOCALIZATION; MECHANISMS; ABSORPTION; SUBTYPES AB In the kidney, endothelins (ETs) are important regulators of blood flow, glomerular hemodynamics, and sodium and water homeostasis. They have been implicated in the pathophysiology of acute ischemic renal failure, nephrotoxicity by cyclosporine, cisplatin and radiocontrast agents, and vascular rejection of kidney transplants. Here, we used intact killifish renal proximal tubules, fluorescent substrates for Mrp2 (fluorescein-methotrexate, FL-MTX) and P-glycoprotein (a fluorescent CSA derivative, NBD-CSA), and confocal microscopy to reveal a new role for renal ET: regulation of ATP-driven drug transport in proximal tubule. Subnanomolar to nanomolar concentrations of ET-1 rapidly reduced the cell-to-tubular lumen transport of both fluorescent compounds. These effects were prevented by an ETB receptor antagonist but not by an ETA receptor antagonist. Immunostaining with an antibody to mammalian ETB receptors showed specific localization to the basolateral membrane of the fish tubular epithelial cells. ET-1 effects on transport were blocked by protein kinase C-selective inhibitors, implicating protein kinase C in ET-1 signaling. Finally, the nephrotoxic radiocontrast agent iohexol reduced cell-to-lumen FL-MTX and NBD-CSA transport, and these effects were abolished by an ETB receptor antagonist. These are the first results linking ET to the control of xenobiotic transport and the first demonstrating control of renal multidrug resistance-associated protein 2 and P-glycoprotein by a hormone. C1 Catholic Univ Nijmegen, Dept Pharmacol & Toxicol 233, NL-6500 HB Nijmegen, Netherlands. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME USA. RP Masereeuw, R (reprint author), Catholic Univ Nijmegen, Dept Pharmacol & Toxicol 233, POB 9101, NL-6500 HB Nijmegen, Netherlands. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014; OI Russel, Frans/0000-0002-7959-2314; Masereeuw, Rosalinde/0000-0002-1560-1074 NR 43 TC 72 Z9 76 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2000 VL 57 IS 1 BP 59 EP 67 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 271EB UT WOS:000084580300008 PM 10617679 ER PT J AU Schetz, JA Benjamin, PS Sibley, DR AF Schetz, JA Benjamin, PS Sibley, DR TI Nonconserved residues in the second transmembrane-spanning domain of the D-4 dopamine receptor are molecular determinants of D-4-selective pharmacology SO MOLECULAR PHARMACOLOGY LA English DT Article ID BINDING-SITE CREVICE; PROTEIN-COUPLED RECEPTORS; SELECTIVE AGONIST BINDING; DELTA-OPIOID RECEPTOR; D2 RECEPTOR; EXTRACELLULAR LOOP; ANTAGONIST BINDING; IDENTIFICATION; SEGMENT; LIGANDS AB The molecular determinants that govern selective ligand binding to the rat D-4 dopamine receptor were investigated by substituting D-2 dopamine receptor sequences into a D-4 dopamine receptor background. The resulting mutant D-4 dopamine receptors were then screened with a panel of 10 selective and nonselective ligands, which included two allosteric modulators as sensitive measures of protein conformational changes. Mutation of a phenylalanine at position 88 in the second transmembrane-spanning domain (TMS2) of the D-4 receptor to the corresponding valine in the D-2 receptor D-4-F88V resulted in an similar to 100-fold decrease in the affinity of the highly D-4-selective drug 3-{[4-(4-iodophenyl) piperazin-1-yl]methyl}-1H-pyrrolo[2,3-b]pyridine (L-750,667) without substantially affecting the binding of the other ligands. Mutations at the extracellular side of D-4-TMS3 produced moderate decreases in L-750,667 binding affinities with concomitant increases in binding affinity for the D-2/D-3-selective antagonist (-)-raclopride. However, the binding affinities of these same D-4-TMS3 mutants for the allosteric modulator isomethylbutylamiloride also were an anomalous 6- to 20-fold higher than either wild-type receptor. In the combined D-4-F88V/TMS3 mutants, L-750,667 binding affinity was further decreased, but this decrease was not additive. More importantly, the combined D-4-F88V/TMS3 mutants had (2)- raclopride and isomethylbutylamiloride binding properties that reverted back to those of the wild-type D-4-receptor. In contrast to the D-4-F88V mutant, the adjacent D-4-L87W mutant had an increased affinity for ligands with extended structures, but had essentially no effect on ligands with compact structures. These findings demonstrate that two residues near the extracellular side of D-4-TMS2 are critical molecular determinants for the selective binding of L-750,667 and ligands with extended structures. C1 NINCDS, Expt Therapeut Branch, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. RP Schetz, JA (reprint author), NINCDS, Expt Therapeut Branch, Mol Neuropharmacol Sect, NIH, Bldg 10,Room 5C 108,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 25 Z9 25 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2000 VL 57 IS 1 BP 144 EP 152 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 271EB UT WOS:000084580300018 PM 10617689 ER PT J AU Verdier-Pinard, P Kepler, JA Pettit, GR Hamel, E AF Verdier-Pinard, P Kepler, JA Pettit, GR Hamel, E TI Sustained intracellular retention of dolastatin 10 causes its potent antimitotic activity SO MOLECULAR PHARMACOLOGY LA English DT Article ID VINCA ALKALOIDS; CELL-LINES; MICROTUBULE DYNAMICS; P-GLYCOPROTEIN; LYMPHOMA-CELLS; TUBULIN; VINBLASTINE; BINDING; VINCRISTINE; INHIBITION AB Dolastatin 10 is a highly cytotoxic antimitotic peptide in phase II clinical trials. Its cytotoxicity has been as much as 50-fold greater than that of vinblastine, despite quantitatively similar effects of the two drugs on tubulin polymerization. We compared uptake and efflux of radiolabeled dolastatin 10 and vinblastine in human Burkitt lymphoma CA46 cells to gain an understanding of the greater cytotoxicity of the peptide. In the Burkitt cells, dolastatin 10 was 20-fold more cytotoxic than vinblastine (IC50 values, 50 pM and 1.0 nM). When drug uptake at 24 h was compared at IC50 values of the two drugs, the intracellular concentrations were almost identical (50-100 nM). The accumulation factor observed for dolastatin 10 was 900 to 1800 versus 60 to 100 for vinblastine. The two drugs showed very divergent uptake kinetics, however. Vinblastine and dolastatin 10 reached maximum intracellular concentrations after 20 min and 6 h, respectively. Depletion of cellular ATP content did not alter the uptake of either drug, indicating passive uptake of both. When drug-preloaded cells were transferred to drug-free medium, there was no loss of dolastatin 10 for at least 2 h, whereas vinblastine exited the cells rapidly (approximate intracellular half-life, 10 min), with less than 10% of the initial drug remaining in the cells after the 2-h incubation. The potency of dolastatin 10 probably derives from its tenacious binding to tubulin, a property that in cells becomes translated into prolonged intracellular retention of the drug. Optimal clinical use of dolastatin 10 may require administration by infusion rather than by bolus. C1 NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Lab Drug Discovery Res & De, Frederick, MD 21702 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem, Tempe, AZ 85287 USA. RP Hamel, E (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag, Dev Therapeut Program,Lab Drug Discovery Res & De, Bldg 469,Room 237, Frederick, MD 21702 USA. NR 40 TC 25 Z9 26 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2000 VL 57 IS 1 BP 180 EP 187 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 271EB UT WOS:000084580300022 PM 10617693 ER PT J AU Hamer, D Sirota, L AF Hamer, D Sirota, L TI Beware the chopsticks gene SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID ASSOCIATION; DISEQUILIBRIUM; LINKAGE C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Hamer, D (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Rm YA13, Bethesda, MD 20892 USA. NR 12 TC 58 Z9 58 U1 1 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2000 VL 5 IS 1 BP 11 EP 13 DI 10.1038/sj.mp.4000662 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 281MX UT WOS:000085165600006 PM 10673763 ER PT J AU Morris, JC Wildner, O AF Morris, JC Wildner, O TI Therapy of head and neck squamous cell carcinoma with an oncolytic adenovirus expressing HSV-tk SO MOLECULAR THERAPY LA English DT Article DE gene therapy; replication-competent adenovirus; HSV-1-tk/ganciclovir; head and neck cancer ID LATE GENE-EXPRESSION; P53 STATUS; MONOCLONAL-ANTIBODIES; NUCLEOSIDE ANALOGS; THYMIDINE KINASE; MESSENGER-RNA; BRAIN-TUMORS; SUICIDE GENE; IN-VIVO; CANCER AB Currently available therapeutic modalities for advanced head and neck squamous cell carcinoma (HNSCC), such as radical surgery, high-dose radiotherapy, and chemotherapy, are of limited efficacy. Overall survival has not significantly improved over the past 30 years; thus, HNSCC represents a promising target for new therapeutic approaches, such as gene therapy. A major obstacle to the development of effective suicide gene therapy strategies that rely on in situ transduction of tumor cells is the poor distribution of the vector throughout the tumor. To address this problem we evaluated the use of Ad.OW34, an E1b 55 kD and HSV-tk-carrying, replication-competent adenoviral vector that has a wild-type adenovirus phenotype in replicating cells, in combination with ganciclovir (GCV) as a treatment for HNSCC xenografts in nude mice and compared its efficacy with that of a standard replication-deficient adenovirus expressing HSV-tk (Ad.TK). In this model, Ad.OW34 had a significantly greater antitumor effect than the traditional Ad.TK vector, administered alone or in combination with GCV. Interestingly, GCV did not further enhance the oncolytic efficacy of Ad.OW34. GCV also aborts viral replication and thus represents a fail-safe feature of this vector not found in wild-type adenovirus. C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Wildner, O (reprint author), NHGRI, Clin Gene Therapy Branch, NIH, Bldg 10,Room 10C103, Bethesda, MD 20892 USA. NR 42 TC 61 Z9 62 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JAN PY 2000 VL 1 IS 1 BP 56 EP 62 DI 10.1006/mthe.1999.0014 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 366RL UT WOS:000090018300011 PM 10933912 ER PT J AU Metman, LV Konitsiotis, S Chase, TN AF Metman, LV Konitsiotis, S Chase, TN TI Pathophysiology of motor response complications in Parkinson's disease: Hypotheses on the why, where, and what SO MOVEMENT DISORDERS LA English DT Editorial Material ID LEVODOPA-INDUCED DYSKINESIAS; LONG-TERM TREATMENT; CENTRAL DOPAMINERGIC MECHANISMS; PROGRESSIVE SUPRANUCLEAR PALSY; NMDA RECEPTOR BLOCKADE; L-DOPA; BASAL GANGLIA; NIGROSTRIATAL DAMAGE; SUPER-SENSITIVITY; D2 DOPAMINE C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Metman, LV (reprint author), NINDS, Expt Therapeut Branch, NIH, Bldg 10,Room 5C104,10 Ctr Dr MSC 1406, Bethesda, MD 20892 USA. NR 64 TC 61 Z9 62 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 2000 VL 15 IS 1 BP 3 EP 8 DI 10.1002/1531-8257(200001)15:1<3::AID-MDS1003>3.0.CO;2-E PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 269WM UT WOS:000084500600002 PM 10634235 ER PT J AU Hallett, M AF Hallett, M TI Physiology of human posthypoxic myoclonus SO MOVEMENT DISORDERS LA English DT Article; Proceedings Paper CT Workshop on Posthypoxic Myoclonus CY MAR 21-22, 1999 CL WASHINGTON, D.C. SP NINDS, Off Rare Dis, NIH, Myoclonus Res Fdn ID EPILEPTIC NEGATIVE MYOCLONUS; REFLEX MYOCLONUS; POSTANOXIC COMA; STARTLE REFLEX AB There are two types of posthypoxic myoclonus. acute and chronic. The acute type has not been intensively studied but is likely to be brain stem in origin. Chronic posthypoxic myoclonus is most commonly cortical reflex myoclonus, but reticular reflex myoclonus and exaggerated startle may also occur. These three conditions have characteristic physiological features. In assessing the relevance of an animal model, it would be appropriate to identify the myoclonus with one of these three patterns. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1428, Bethesda, MD 20892 USA. NR 30 TC 39 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PY 2000 VL 15 SU 1 BP 8 EP 13 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 295LW UT WOS:000085968800003 PM 10755266 ER PT J AU Ludlow, CL Bielamowicz, S Rosenberg, MD Ambalavanar, R Rossini, K Gillespie, M Hampshire, V Testerman, R Erickson, D Carraro, U AF Ludlow, CL Bielamowicz, S Rosenberg, MD Ambalavanar, R Rossini, K Gillespie, M Hampshire, V Testerman, R Erickson, D Carraro, U TI Chronic intermittent stimulation of the thyroarytenoid muscle maintains dynamic control of glottal adduction SO MUSCLE & NERVE LA English DT Article DE neuroprosthesis; dysphagia; canine; larynx; airway protection ID LARYNGEAL NERVE STIMULATOR; ELECTRICAL-STIMULATION; SPASTIC DYSPHONIA; CANINE; CLOSURE; IMPLANTATION; ISOMYOSINS; ASPIRATION; PARALYSIS; SWALLOW AB Patients with laryngeal motor control disorders need improved dynamic glottal closure far speech and swallowing. To evaluate the functional outcome of intermittent chronic thyroarytenoid muscle stimulation in an animal model, 6 canines were implanted with bilateral Medtronic Xtrel systems containing Peterson-type electrodes in the inferior and superior portions of the thyroarytenoid muscle. Stimulation was on one side only at 60 Hz, for 5 s on and 5 s off, over 8 h, 5 days per week, up to 8 months. Monthly videorecordings were done under anesthesia to measure the voltage threshold for detectable movement on each side, and vocal ford displacement and velocity during maximal stimulation of each side. Movement thresholds were tower in the inferior portion of the thyroarytenoid muscle (P less than or equal to 0.0005). Movement velocity was greater on the stimulated than on the nonstimulated side after 3 to 8 months (P = 0.039). No differences in the percentage distribution of different myosin heavy chain types were found between the stimulated and nonstimulated muscle samples. Sustained dynamic glottal adduction with no alteration in thyroarytenoid muscle function or fiber type was achieved with intermittent stimulation over 8 months. The results suggest that chronic intermittent thyroarytenoid stimulation has good potential for improving airway protection in dysphagia. (C) 2000 John Wiley & Sons, Inc. C1 NINCDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Div Otolaryngol Head & Neck Surg, Washington, DC USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. Medtron Inc, Minneapolis, MN USA. Univ Padua, Dept Biomed Sci, CNR, Unit Muscle Biol & Pathophysiol, Padua, Italy. RP Ludlow, CL (reprint author), NINCDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bldg 10,Room 5D38,10 Ctr Dr,MSC 1416, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 47 TC 8 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JAN PY 2000 VL 23 IS 1 BP 44 EP 57 DI 10.1002/(SICI)1097-4598(200001)23:1<44::AID-MUS6>3.0.CO;2-E PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 269GC UT WOS:000084467500005 PM 10590405 ER PT J AU Kelecsenyi, Z Spencer, DL Caspary, WJ AF Kelecsenyi, Z Spencer, DL Caspary, WJ TI Molecular analysis of 5-azacytidine-induced variants in mammalian cells SO MUTAGENESIS LA English DT Article ID CANCER CHEMOTHERAPEUTIC-AGENTS; SISTER-CHROMATID EXCHANGES; HAMSTER EMBRYO FIBROBLASTS; AS52 CELLS; ESCHERICHIA-COLI; DNA METHYLATION; MORPHOLOGICAL TRANSFORMATION; SALMONELLA-TYPHIMURIUM; C3H-10T1/2 CLONE-8; CYTIDINE ANALOGS AB 5-Azacytidine induces 6-thioguanine resistance in AS52 cells. To characterize these resistant clones, we isolated 148 of them from 50 independently treated flasks. Less than nine (6%) of the 148 variants were spontaneous. PCR amplification of the DNA primers flanking the gpt gene produced no product in 15 clones (10%), Of the 133 remaining clones, 52 showed sequence alterations in the gpt structural gene. Of these 52, 34 (65%) were GC-->CG transversions. Only seven were located in CPG sequences, Thus, methyltransferase complexes are not major contributors to 5-azacytidine-induced point mutations in AS52 cells, The remaining 81 clones had no sequence alterations within the coding region of the gpt gene, Southern blot analysis of a sample of these variants (37/81) indicated that the 6-thioguanine-resistant phenotype was not due to local rearrangements or deletions (resolution 50 bp), Sequence analysis of the early promoter region of another sample of these variants (24/81) indicated that lesions in the promoter could not be responsible for the 6-thioguanine resistance observed, Thus, a majority of these variants were formed via a mechanism other than small genomic rearrangements, point mutations or deletions of the gpt structural gene or its promoter. Neither the mechanisms leading to these variants nor the biological and morphological consequences of these variants are known. C1 NIH, Canc Genet Grp, Res Triangle Pk, NC 27709 USA. Orszagos Kemiai Biztonsagi Intezet Gyali, H-1966 Budapest, Hungary. RP Caspary, WJ (reprint author), NIH, Canc Genet Grp, Res Triangle Pk, NC 27709 USA. NR 53 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JAN PY 2000 VL 15 IS 1 BP 25 EP 31 DI 10.1093/mutage/15.1.25 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 278BZ UT WOS:000084969200004 PM 10640527 ER PT J AU Preisler, V Caspary, WJ Hoppe, F Hagen, R Stopper, H AF Preisler, V Caspary, WJ Hoppe, F Hagen, R Stopper, H TI Aflatoxin B1-induced mitotic recombination in L5178Y mouse lymphoma cells SO MUTAGENESIS LA English DT Article ID HUMAN HEPATOCELLULAR CARCINOMAS; KI-RAS ONCOGENE; P53 GENE; RECESSIVE ALLELES; MAMMALIAN-CELLS; LIVER-TUMORS; DNA ADDUCTS; IN-SITU; HETEROZYGOSITY; EXPRESSION AB Aflatoxin B1 is a human hepatocarcinogen, It is also a known point mutagen in bacteria and mammalian cells. This mutagenic activity may be at least partly responsible for its carcinogenic activity. However, recent studies show that aflatoxin B1 induces mitotic recombination in the yeast Saccharomyces cerevisiae, Because numerous reports have implicated mitotic recombination in mechanisms leading to carcinogenesis and because no one has shown that aflatoxin B1 induces recombination in mammalian cells, we decided to examine the ability of aflatoxin B1 to induce recombination in a mammalian cell line. We used a combination of methods, analysis for loss of heterozygosity and whole chromosome in situ hybridization, to identify mechanisms of chromosome mutation, including mitotic recombination in the mammalian L5178Y mouse lymphoma cell system. Our experiments revealed that mitotic recombination caused similar to 60% or more of the aflatoxin B1-induced mutagenic lesions in this cell system. Thus, mitotic recombination plays an important role in aflatoxin B1-induced mutagenesis in mammalian cells and possibly in chemically induced mutagenesis and carcinogenesis. This work suggests that multiple genetic lesions may be involved in aflatoxin B1-induced pathology. C1 NIH, Res Triangle Pk, NC 27709 USA. Univ Wurzburg, Dept Otorhinolaryngol, D-97078 Wurzburg, Germany. Univ Wurzburg, Dept Toxicol, D-97078 Wurzburg, Germany. RP Caspary, WJ (reprint author), NIH, Res Triangle Pk, NC 27709 USA. NR 48 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JAN PY 2000 VL 15 IS 1 BP 91 EP 97 DI 10.1093/mutage/15.1.91 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 278BZ UT WOS:000084969200013 PM 10640536 ER PT S AU Froehlich, JP Bamberg, E Kane, DJ Mahaney, JE Albers, RW AF Froehlich, JP Bamberg, E Kane, DJ Mahaney, JE Albers, RW BE Taniguchi, K Kaya, S TI Contribution of quaternary protein interactions to the mechanism of energy transduction in Na+/K+-ATPase SO NA/K-ATPASE AND RELATED ATPASES SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 9th International Conference on the Na/K-ATPase and Related ATPases CY AUG 18-23, 1999 CL SAPPORO, JAPAN SP Minist Educ, Sport & Culture Japan, Pharmaceut Mfg Assoc Tokyo, Osaka Pharmaceut Mfg Assoc, Oriental Yeast Co Ltd, ITo Sci Co Ltd, Astec Co Ltd, Hokkaido Prefecture, Naito Fdn, Akiyama Sci Fdn, Nagase Sci & Technol Fdn, Uehara Mem Fdn, Novartis Sci Fdn, Ito Fdn Promot Med Sci ID STEADY-STATE; NA,K-ATPASE; NA+,K+-ATPASE; DEPHOSPHORYLATION; TRIPHOSPHATASE; BINDING; SITE C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Froehlich, JP (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50421-4 J9 INT CONGR SER PY 2000 VL 1207 BP 349 EP 356 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BS27Z UT WOS:000169355900059 ER PT S AU Bagrov, AY Lakatta, EG Fedorova, OV AF Bagrov, AY Lakatta, EG Fedorova, OV BE Taniguchi, K Kaya, S TI Marinobufagenin, an endogenous bufodienolide sodium pump inhibitor SO NA/K-ATPASE AND RELATED ATPASES SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 9th International Conference on the Na/K-ATPase and Related ATPases CY AUG 18-23, 1999 CL SAPPORO, JAPAN SP Minist Educ, Sport & Culture Japan, Pharmaceut Mfg Assoc Tokyo, Osaka Pharmaceut Mfg Assoc, Oriental Yeast Co Ltd, ITo Sci Co Ltd, Astec Co Ltd, Hokkaido Prefecture, Naito Fdn, Akiyama Sci Fdn, Nagase Sci & Technol Fdn, Uehara Mem Fdn, Novartis Sci Fdn, Ito Fdn Promot Med Sci ID DIGITALIS-LIKE; VOLUME EXPANSION; RAT AORTA; OUABAIN; NA,K-ATPASE; NA+,K+-ATPASE; HYPERTENSION; HYPOVENTILATION; ATPASE; TOAD C1 NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NR 29 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50421-4 J9 INT CONGR SER PY 2000 VL 1207 BP 647 EP 654 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BS27Z UT WOS:000169355900117 ER PT S AU Fedorova, OV Lakatta, EG Bagrov, AY AF Fedorova, OV Lakatta, EG Bagrov, AY BE Taniguchi, K Kaya, S TI Marinobufagenin and cardiovascular remodeling in Dahl rats on a high NaCl diet SO NA/K-ATPASE AND RELATED ATPASES SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 9th International Conference on the Na/K-ATPase and Related ATPases CY AUG 18-23, 1999 CL SAPPORO, JAPAN SP Minist Educ, Sport & Culture Japan, Pharmaceut Mfg Assoc Tokyo, Osaka Pharmaceut Mfg Assoc, Oriental Yeast Co Ltd, ITo Sci Co Ltd, Astec Co Ltd, Hokkaido Prefecture, Naito Fdn, Akiyama Sci Fdn, Nagase Sci & Technol Fdn, Uehara Mem Fdn, Novartis Sci Fdn, Ito Fdn Promot Med Sci ID MYOCARDIAL-INFARCTION; K+-ATPASE; CONSEQUENCES; HYPERTENSION; HYPERTROPHY; NA,K-ATPASE; OUABAIN; NA+ C1 NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Fedorova, OV (reprint author), NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50421-4 J9 INT CONGR SER PY 2000 VL 1207 BP 685 EP 688 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BS27Z UT WOS:000169355900122 ER PT B AU Walker, FL Thoma, GR AF Walker, FL Thoma, GR BE Williams, ME TI Read it to me! SO NATIONAL ONLINE MEETING, PROCEEDINGS 2000 LA English DT Proceedings Paper CT 21st National Online Meeting CY MAY 16-18, 2000 CL NEW YORK, NY SP Informat Today Inc, Lexis Nexis DE DocMorph Server; speech synthesis; image processing; World Wide Web; TIFF; PDF; OCR; DocView; NLM; Ariel; Internet AB New technology and software such as Ariel and DocView have made it possible for libraries to distribute information to patrons over the Internet. Ariel, a product of the Research Libraries Group, converts paper-based documents to monochrome bitmapped images, and delivers them over the Internet, while the National Library of Medicine's DocView enables library patrons to receive, display and manage documents received from Ariel systems. While libraries and their patrons are beginning to reap the benefits of this new technology, both technological and social barriers still exist that lead to difficulties in the use of library document information. For example, the formats of files received through the Internet may not be usable on the recipient's computer. In addition, disadvantaged groups of people such as the blind and visually impaired often have difficulties in reading either printed or electronic information. To investigate solutions to some of these barriers, the Communications Engineering Branch of the Lister Hill National Center for Biomedical Communications, an R&D division of NLM, has developed a web site called the DocMorph Server. This is part of an ongoing R&D program in document imaging that has spanned many aspects of electronic document conversion and preservation, Internet document transmission and document usage. The DocMorph Server web site allows users to upload document image files via the Internet for conversion to alternative formats (e.g., TIFF to PDF), thereby enabling wider delivery and easier usage of library document information. A recent development in the DocMorph Server is speech synthesis to permit users to convert scanned images of the printed word into the spoken word. From any place on the Internet, a user can upload scanned images of a book, for example, and have DocMorph return a web page that allows the user's computer to read the material out loud. This reading facility enables certain groups of people to read material that would otherwise be difficult or impossible to read. This paper describes the architecture of the prototype DocMorph Server and the design of its computer-assisted reading facility. C1 Natl Lib Med, Bethesda, MD 20894 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055 USA BN 1-57387-102-8 PY 2000 BP 473 EP 483 PG 11 WC Information Science & Library Science SC Information Science & Library Science GA BR04Z UT WOS:000165502800047 ER PT S AU Abu-Raya, S Bloch-Shilderman, E Jiang, H Adermann, K Schaefer, EM Goldin, E Yavin, E Lazarovici, P AF Abu-Raya, S Bloch-Shilderman, E Jiang, H Adermann, K Schaefer, EM Goldin, E Yavin, E Lazarovici, P BE Tu, AT Gaffield, W TI Cellular signaling in PC12 affected by pardaxin SO NATURAL AND SELECTED SYNTHETIC TOXINS: BIOLOGICAL IMPLICATIONS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT 216th National Meeting of the American-Chemical-Society CY AUG 21-27, 1998 CL BOSTON, MASSACHUSETTS SP Amer Chem Soc, Div Polymer Mat, Sci & Engn Inc, Div Polymer Mat, Exxon Res & Engn CO, Amer Chem Soc, Petr Res Fund, Amer Chem Soc, Div Fluorine Chem, Amer Chem Soc, Div Organ Chem, Amer Chem Soc, Corp Associates, Dow Agrosci, Monsanto Co, Eastman Kodak Co, Schering Plough, Merck Res Labs, Cent Glass Int Inc, Daikin Ind, Kanto Denka Kogyo Co, Asahi Glass Co, Div Agr & Food Chem ID ADRENAL CHROMAFFIN CELLS; SEA MOSES SOLE; ARACHIDONIC-ACID; NEUROTRANSMITTER RELEASE; CATECHOLAMINE SECRETION; PARDACHIRUS-MARMORATUS; PHOSPHOLIPASE A(2); DEFENSE SECRETION; CHANNEL FORMATION; CALCIUM-ENTRY AB Pardaxins, a family of polypeptide, excitatory neurotoxins, isolated from the gland's secretion of Pardachirus fish are used as pharmacological tools to investigate calcium-dependent and calcium-independent signaling leading to neurotransmitter release. In PC12 cells, a neural model to study exocytosis, pardaxin forms voltage-dependent pores which are involved in pardaxin-induced increase in intracellular calcium and calcium-dependent dopamine release. Pardaxin-induced calcium-independent, dopamine release from PC12 cells is attributed to the stimulation of the arachidonic acid cascade and the increased release of the arachidonic acid metabolites produced by the lipoxygenase pathways. Pardaxin rapidly stimulates MAPK phosphorylation activity, which is proposed to be involved in pardaxin-induced arachidonic acid and dopamine release. It seems likely that pardaxin delayed stimulation of stress-kinases JNK and p38 will play a prominent role in triggering cell death. Collectively, these results demonstrate that pardaxin selectively modulates neuronal signaling to achieve massive exocytosis and neurotoxicity. C1 Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Dept Pharmacol, Jerusalem, Israel. NICHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Niedersaechs Inst Peptide Forsch, D-30625 Hannover, Germany. Promega Co, Madison, WI 53711 USA. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP Lazarovici, P (reprint author), Hebrew Univ Jerusalem, Fac Med, Sch Pharm, Dept Pharmacol, Jerusalem, Israel. NR 49 TC 1 Z9 1 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3630-5 J9 ACS SYM SER PY 2000 VL 745 BP 22 EP 42 PG 21 WC Chemistry, Multidisciplinary; Toxicology SC Chemistry; Toxicology GA BP75P UT WOS:000086072600003 ER PT J AU Rashid, MA Gustafson, KR Cardellina, JH Boyd, MR AF Rashid, MA Gustafson, KR Cardellina, JH Boyd, MR TI A new podophyllotoxin derivative from Bridelia ferruginea SO NATURAL PRODUCT LETTERS LA English DT Article DE Bridelia ferruginea; podophyllotoxin; glycosides; cytostatic activity; tubulin ID TUMOR-CELL-LINES; ARYLTETRALIN LIGNANS AB Bioassay-guided fractionation of an extract of Bridelia ferruginea provided a new glycoside, 5'-demethoxy-beta-peltatin-5-O-beta-D-glucopyranoside (1), and three known compounds, beta-peltatin (2), beta-peltatin-5-O-beta-D-glucopyranoside (3), and desoxypodophyllotoxin (4). The structure of 1 was elucidated by detailed NMR analyses and by comparison of its spectral data with related compounds. Compounds 1 and 3 exhibited cytotoxic and cytostatic activity in the NCI's 60 cell antitumor screen. C1 NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. NR 17 TC 16 Z9 18 U1 0 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1057-5634 J9 NAT PROD LETT JI Nat. Prod. Lett. PY 2000 VL 14 IS 4 BP 285 EP 292 DI 10.1080/10575630008041244 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 344AJ UT WOS:000088735200008 ER PT J AU Rashid, MA Gustafson, KR Boyd, MR AF Rashid, MA Gustafson, KR Boyd, MR TI Pellynol I, a new cytotoxic polyacetylene from the sponge Pellina sp. SO NATURAL PRODUCT LETTERS LA English DT Article DE pellynol; polyacetylene; Pellina; cytotoxic activity ID MARINE SPONGE AB Bioassay-guided fractionation of an organic extract of a South African collection of the sponge Pellina sp. afforded six polyacetylenic metabolites. These were identified as pellynols A-D, pellynol F, and a new compound, pellynol I (1). The structure of 1 was elucidated by NMR and MS analyses and by comparison of its spectral data with related compounds. The six pellynols all exhibited cytotoxic activity against human tumor cell lines. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. NR 14 TC 10 Z9 10 U1 0 U2 4 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1057-5634 J9 NAT PROD LETT JI Nat. Prod. Lett. PY 2000 VL 14 IS 5 BP 387 EP 392 DI 10.1080/10575630008043772 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 361UH UT WOS:000089742200010 ER PT J AU Beutler, JA Jato, J Cragg, GM Boyd, MR AF Beutler, JA Jato, J Cragg, GM Boyd, MR TI Schweinfurthin D, a cytotoxic stilbene from Macaranga schweinfurthii SO NATURAL PRODUCT LETTERS LA English DT Article DE stilbene; cytotoxicity; Macaranga; Euphorbiaceae AB A novel cytotoxic stilbene, schweinfurthin D, was isolated from Macaranga schweinfurthii (Euphorbiaceae) and its structure was determined by spectroscopic methods. Schweinfurthin D showed comparable potency to schweinfurthin B. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. Univ Yaounde, Fac Med & Biomed Sci, Yaounde, Cameroon. NCI, Nat Prod Branch, DTP, DCTD, Bethesda, MD 20892 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 4 TC 24 Z9 24 U1 1 U2 7 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1057-5634 J9 NAT PROD LETT JI Nat. Prod. Lett. PY 2000 VL 14 IS 5 BP 399 EP 404 DI 10.1080/10575630008043774 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 361UH UT WOS:000089742200012 ER PT J AU Daly, JW Garraffo, HM Spande, TF Decker, MW Sullivan, JP Williams, M AF Daly, JW Garraffo, HM Spande, TF Decker, MW Sullivan, JP Williams, M TI Alkaloids from frog skin: the discovery of epibatidine and the potential for developing novel non-opioid analgesics SO NATURAL PRODUCT REPORTS LA English DT Review ID NICOTINIC ACETYLCHOLINE-RECEPTORS; IN-VITRO CHARACTERIZATION; POISON FROG; (S)-3-METHYL-5-(1-METHYL-2-PYRROLIDINYL)ISOXAZOLE ABT-418; CHOLINERGIC RECEPTORS; ANXIOLYTIC ACTIVITIES; SODIUM-CHANNEL; HIGH-AFFINITY; RAY-ANALYSIS; LIGAND C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Abbott Labs, Div Pharmaceut Prod, Abbott Pk, IL 60064 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 49 TC 74 Z9 75 U1 2 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0265-0568 J9 NAT PROD REP JI Nat. Prod. Rep. PY 2000 VL 17 IS 2 BP 131 EP 135 DI 10.1039/a900728h PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 307HG UT WOS:000086647200002 PM 10821107 ER PT J AU Newman, DJ Cragg, GM Snader, KM AF Newman, DJ Cragg, GM Snader, KM TI The influence of natural products upon drug discovery SO NATURAL PRODUCT REPORTS LA English DT Review ID CYCLIN-DEPENDENT KINASES; ANTIMALARIAL AGENT ARTEMISININ; CEPHALOSPORIN 3'-QUINOLONE ESTERS; IMMUNODEFICIENCY-VIRUS PROTEASE; ANGIOTENSIN-CONVERTING ENZYME; NATIONAL-CANCER-INSTITUTE; BETA-LACTAM ANTIBIOTICS; BIOLOGICAL EVALUATION; BRYOSTATIN ANALOGS; PHASE-I C1 NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. NCI, Pharmaceut Resources Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. RP Newman, DJ (reprint author), NCI, Nat Prod Branch, POB B, Frederick, MD 21702 USA. NR 203 TC 574 Z9 600 U1 14 U2 110 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0265-0568 J9 NAT PROD REP JI Nat. Prod. Rep. PY 2000 VL 17 IS 3 BP 215 EP 234 DI 10.1039/a902202c PG 20 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 316DG UT WOS:000087151900002 PM 10888010 ER PT J AU Burkhart, JG AF Burkhart, JG TI Fishing for mutations SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Burkhart, JG (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. NR 4 TC 2 Z9 3 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2000 VL 18 IS 1 BP 21 EP 22 DI 10.1038/71869 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 273GQ UT WOS:000084699900015 PM 10625381 ER PT J AU Lipkin, SM Wang, V Jacoby, R Banerjee-Basu, S Baxevanis, AD Lynch, HT Elliott, RM Collins, FS AF Lipkin, SM Wang, V Jacoby, R Banerjee-Basu, S Baxevanis, AD Lynch, HT Elliott, RM Collins, FS TI MLH3: a DNA mismatch repair gene associated with mammalian microsatellite instability SO NATURE GENETICS LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; COLON-TUMOR SUSCEPTIBILITY; MICE DEFICIENT; MUTATION; MOUSE; PMS2; DATABASE; TISSUES; CELLS; MSH6 AB DNA mismatch repair is important because of its role in maintaining genomic integrity and its association with hereditary non-polyposis colon cancer (HNPCC). To identify new human mismatch repair proteins, we probed nuclear extracts with the conserved carboxy-terminal MLH1 interaction domain. Here we describe the cloning and complete genomic sequence of MLH3, which encodes a new DNA mismatch repair protein that interacts with MLH1. MLH3 is more similar to mismatch repair proteins from yeast, plants, worms and bacteria than to any known mammalian protein, suggesting that its conserved sequence may confer unique functions in mice and humans. Cells in culture stably expressing a dominant-negative MLH3 protein exhibit microsatellite instability. MIh3 is highly expressed in gastrointestinal epithelium and physically maps to the mouse complex trait locus colon cancer susceptibility I (Ccs1). Although we were unable to identify a mutation in the protein-coding region of MIh3 in the susceptible mouse strain, colon tumours from congenic Ccs1 mice exhibit microsatellite instability. Functional redundancy among MIh3, Pms1 and Pms2 may explain why neither Pms1 nor Pms2 mutant mice develop colon cancer, and why PMS1 and PMS2 mutations are only rarely found in HNPCC families. C1 NIH, Natl Ctr Human Genome Res Inst, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NIH, Natl Ctr Human Genome Res Inst, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Med, Div Gastroenterol, Madison, WI USA. New York State Dept Hlth, Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Creighton Univ, Hereditary Canc Inst, Omaha, NE 68178 USA. RP Collins, FS (reprint author), NIH, Natl Ctr Human Genome Res Inst, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA62225] NR 49 TC 194 Z9 203 U1 0 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2000 VL 24 IS 1 BP 27 EP 35 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 271TH UT WOS:000084609200011 PM 10615123 ER PT J AU Ray, SC Quinn, TC AF Ray, SC Quinn, TC TI Sex and the genetic diversity of HIV-1 SO NATURE MEDICINE LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; GENITAL SECRETIONS; SEROCONVERSION; TRANSMISSION; RESERVOIR; BLOOD; RNA AB The genetic variability of HIV-1 is an important aspect of its pathogenesis, even though studies in men have demonstrated that the viral population is usually homogeneous during the first months of infection. Now, a large study comparing men and women shows that even before an antibody response is detectable, the viral population differs between the sexes (pages 71-75). C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Ray, SC (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. RI Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 NR 19 TC 10 Z9 10 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JAN PY 2000 VL 6 IS 1 BP 23 EP 25 DI 10.1038/71487 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 271FJ UT WOS:000084583300024 PM 10613817 ER PT J AU Hoffman, EA Haxby, JV AF Hoffman, EA Haxby, JV TI Distinct representations of eye gaze and identity in the distributed human neural system for face perception SO NATURE NEUROSCIENCE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; TEMPORAL CORTEX; FUNCTIONAL-ORGANIZATION; FACIAL EXPRESSION; RHESUS-MONKEYS; HUMAN AMYGDALA; ATTENTION; RECOGNITION; ACTIVATION AB Face perception requires representation of invariant aspects that underlie identity recognition as well as representation of changeable aspects, such as eye gaze and expression, that facilitate social communication. Using functional magnetic resonance imaging (fMRI), we investigated the perception of face identity and eye gaze in the human brain. Perception of face identity was mediated more by regions in the inferior occipital and fusiform gyri, and perception of eye gaze was mediated more by regions in the superior temporal sulci. Eye-gaze perception also seemed to recruit the spatial cognition system in the intraparietal sulcus to encode the direction of another's gate and to focus attention in that direction. C1 NIMH, Sect Funct Brain Imaging, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Hoffman, EA (reprint author), NIMH, Sect Funct Brain Imaging, Lab Brain & Cognit, Bldg 10,Room 4C104, Bethesda, MD 20892 USA. NR 46 TC 712 Z9 728 U1 8 U2 77 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2000 VL 3 IS 1 BP 80 EP 84 DI 10.1038/71152 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 292TB UT WOS:000085810200016 PM 10607399 ER PT J AU Agodoa, L AF Agodoa, L TI United States Renal Data System (USRDS) SO NEFROLOGIA LA English DT Article C1 NIH, USRDS, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA. RP Agodoa, L (reprint author), NIH, USRDS, Div Kidney Urol & Hematol Dis, Bldg 45,Room 6AS13B,45 Ctr Dr, Bethesda, MD 20892 USA. NR 5 TC 8 Z9 8 U1 0 U2 0 PU SOC ESPANOLA NEFROLOGIA DR RAFAEL MATESANZ PI MADRID PA HOSPITAL RAMON Y CAJAL CTR DE COLMENAR, KM 9,100, 28034 MADRID, SPAIN SN 0211-6995 J9 NEFROLOGIA JI Nefrologia PY 2000 VL 20 SU 5 BP 13 EP 16 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 403LK UT WOS:000167043200005 PM 11190101 ER PT J AU Gadlin, H AF Gadlin, H TI The ombudsman: What's in a name? SO NEGOTIATION JOURNAL-ON THE PROCESS OF DISPUTE SETTLEMENT LA English DT Article AB The role of the ombudsman is perhaps the least well understood in the field of alternative dispute resolution (ADR). This essay introduces readers tb the differing conceptions of the role; the sometimes fractious divide that has existed in the past between "classical" and " organizational" ombudsmen; and a collection of essays by four well-known practitioners that shed light on what it is ombudsmen do; the kinds of disputes they deal with and how they operate; how they view their role (and how others view it); and both the possibilities and limitations of the ombuds function. C1 NIH, Ombudsmans Off, Bethesda, MD 20892 USA. RP Gadlin, H (reprint author), NIH, Ombudsmans Off, Bldg 31,Room 1B 39, Bethesda, MD 20892 USA. NR 3 TC 5 Z9 5 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0748-4526 J9 NEGOTIATION J JI Negot. J.-Process Disput. Settl. PD JAN PY 2000 VL 16 IS 1 BP 37 EP 48 PG 12 WC Management; Social Sciences, Interdisciplinary SC Business & Economics; Social Sciences - Other Topics GA 281LH UT WOS:000085161300003 ER PT J AU Theodore, WH Gaillard, WD AF Theodore, WH Gaillard, WD TI Positron emission tomography in neocortical epilepsies SO NEOCORTICAL EPILEPSIES SE ADVANCES IN NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; CEREBRAL GLUCOSE-METABOLISM; COMPLEX PARTIAL SEIZURES; BENZODIAZEPINE-RECEPTOR-BINDING; LENNOX-GASTAUT SYNDROME; MU-OPIATE RECEPTORS; BLOOD-FLOW; LANGUAGE LOCALIZATION; CORTICAL DEVELOPMENT; WORKING-MEMORY C1 NINCDS, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Neurol & Pediat, Washington, DC 20010 USA. RP Theodore, WH (reprint author), NINCDS, NIH, Bethesda, MD 20892 USA. NR 76 TC 6 Z9 6 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-3952 J9 ADV NEUROL JI Adv.Neurol. PY 2000 VL 84 BP 435 EP 446 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BT72X UT WOS:000173887800034 PM 11091886 ER PT J AU Hoffman, JM AF Hoffman, JM TI Imaging in cancer: A National Cancer Institute "extraordinary opportunity" SO NEOPLASIA LA English DT Editorial Material C1 NCI, Biomed Imaging Program, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Hoffman, JM (reprint author), NCI, Biomed Imaging Program, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 36 Z9 36 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JAN-APR PY 2000 VL 2 IS 1-2 BP 5 EP 8 PG 4 WC Oncology SC Oncology GA 305BV UT WOS:000086519700001 PM 10933064 ER PT J AU Feikova, S Wolff, L Bies, J AF Feikova, S Wolff, L Bies, J TI Constitutive ubiquitination and degradation of c-Myb by the 26S proteasome during proliferation and differentiation of myeloid cells SO NEOPLASMA LA English DT Article DE c-Myb; proteolysis; 26S proteasome; ubiquitin; cell cycle ID TRANSFORMATION; PATHWAY; JUN; PROTEOLYSIS; EXPRESSION; KINASES; GROWTH; LEADS AB Steady state levels of transcription factors play an important role in proliferation and differentiation of hematopoietic cells. The transcription factor c-Myb is frequently activated by retrovirus integration in murine and avian leukemias. Its deregulation has been also implicated in human acute and chronic leukemias and some other nonhematopoietic tumors. It is a short-lived protein, which is rapidly degraded by the 26S proteasome. Truncation at the carboxyl (COOH) terminus, which has occurred in some oncogenic forms of c-Myb, results in the increased resistance to proteolysis. This stabilization correlates in vitro with less efficient ubiquitination. Here, we report the first evidence of post-translational modification of c-Myb by ubiquitin in vivo using HA-labeled ubiquitin. We also show that, in contrast to the unstable wild type or amino (NH2)-terminally truncated c-Myb form, stable carboxyl (COOH)-terminally truncated c-Myb is not targeted to degradation by covalent attachment of ubiquitin in vivo. In addition, following an analysis of subcellular fractionation of proteins from cells treated with a 26S proteasome inhibitor we were able to localize c-Myb exclusively in the nuclear compartment, suggesting the absence of a requirement for export to cytoplasm prior proteolytic processing. Furthermore, pulse-chase experiments of c-Myb protein isolated from interphase cells or cells synchronized in the G2/M or G1 phases of cell cycle did not reveal substantial cell cycle dependent differences in proteolytic processing by the 26S proteasome. Also, the demonstration that the half-life of c-Myb in myeloid progenitor M1 cells induced to differentiate along the monocytic pathway is the same as in undifferentiated cells suggested that proteolytic breakdown of c-Myb is a constitutive process during proliferation and differentiation. C1 Slovak Acad Sci, Canc Res Inst, Mol Virol Lab, Bratislava 83392, Slovakia. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Feikova, S (reprint author), Slovak Acad Sci, Canc Res Inst, Mol Virol Lab, Bratislava 83392, Slovakia. NR 22 TC 13 Z9 13 U1 0 U2 0 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57 NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0028-2685 J9 NEOPLASMA JI Neoplasma PY 2000 VL 47 IS 4 BP 212 EP 218 PG 7 WC Oncology SC Oncology GA 345PP UT WOS:000088824600003 PM 11043824 ER PT J AU Metman, LV Del Dotto, P LePoole, K Konitsiotis, S Fang, J Chase, TN AF Metman, LV Del Dotto, P LePoole, K Konitsiotis, S Fang, J Chase, TN TI Amantadine for levodopa-induced dyskinesias SO NERVENHEILKUNDE LA German DT Article DE morbus Parkinson; amantadine; dyskinesias ID PARKINSONS-DISEASE; MOTOR FLUCTUATIONS; BLOCKADE AB Background: In a recent acute study, amantadine was found to have antidyskinetic effect against levodopo-induced motor complications in patients with Parkinson disease. The longevity of this effect was not addressed but is of interest in light of the controversy in the literature regarding the duration of amantadine's well-established antiparkinsonion action. Obiective: To determine the duration of the antidyskinetic effect of amantadine in advanced Parkinson disease. Design. One year after completion of on acute, double-blind, placebo-controlled, crossover study, patients returned for re-evaluation of motor symptoms and dyskinesias using a nonrandomized, double-blind, placebo-controlled follow-up paradigm. Setting: National Institutes of Health Clinical Center. Patients: Seventeen of the original 18 patients with advanced Parkinson disease complicated by dyskinesias and motor fluctuations participated in this study, 1 was lost to follow-vp. Thirteen of the 17 individuals had remained on amantadine therapy for the entire year. Interventions: Ten days prior to the followup assessment, amantadine was replaced with identical capsules containing either amantadine or placebo. Main Outcome Measures: Parkinsonian symptoms and dyskinesia severity were scored using standard rating scales, while subjects received steady-state intravenous levodopa infusions at the same rate as 1 year earlier. Results: One year after initiation of amantadine cotherapy, its antidyskinetic effect was similar in magnitude (56% reduction in dyskinesia compared with 60% 1 year earlier). Motor complications occurring with the patients' regular oral levodopa regimen also remained improved according to the Unified Parkinson's Disease Rating Scale (UPDRS-IV). Conclusion: The beneficial effects of amantadine on motor response complications ore maintained for at least 1 year after treatment initiation. C1 NIH, Bethesda, MD 20892 USA. RP Metman, LV (reprint author), NIH, Bldg 10,Room SC 104,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0722-1541 J9 NERVENHEILKUNDE JI Nervenheilkunde PY 2000 VL 19 IS 5 BP 276 EP 279 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 331MN UT WOS:000088023000012 ER PT S AU Lu, B Gottschalk, W AF Lu, B Gottschalk, W BE Seil, FJ TI Modulation of hippocampal synaptic transmission and plasticity by neurotrophins SO NEURAL PLASTICITY AND REGENERATION SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 8th International Symposium on Neural Regeneration CY DEC 08-12, 1999 CL ASILOMAR CONF CTR, PACIFIC GROVE, CALIFORNIA SP US Dept Vet Affairs, Med Res Serv, Paralyzed Vet Amer, Spin Cord Res Fdn, NINDS, Christopher Reeve Paralysis Fdn, Eastern Paralyzed Vet Assoc HO ASILOMAR CONF CTR ID LONG-TERM POTENTIATION; NERVE GROWTH-FACTOR; DEVELOPING NEUROMUSCULAR SYNAPSES; PAIRED-PULSE FACILITATION; CORTICAL DENDRITIC GROWTH; MESSENGER-RNA EXPRESSION; DEVELOPING VISUAL-CORTEX; POSTNATAL RAT-BRAIN; BDNF KNOCKOUT MICE; DENTATE GYRUS C1 NICHD, Dev Neurobiol Lab, Unit Synapse Dev & Plast, NIH, Bethesda, MD 20892 USA. RP Lu, B (reprint author), NICHD, Dev Neurobiol Lab, Unit Synapse Dev & Plast, NIH, Bldg 49,Room 5A38,49 Convent Dr,MSC 4480, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012 NR 110 TC 97 Z9 102 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50209-2 J9 PROG BRAIN RES PY 2000 VL 128 BP 231 EP 241 PG 11 WC Neurosciences SC Neurosciences & Neurology GA BS30B UT WOS:000169388600019 PM 11105682 ER PT S AU Saavedra, RA Murray, M de Lacalle, S Tessler, A AF Saavedra, RA Murray, M de Lacalle, S Tessler, A BE Seil, FJ TI In vivo neuroprotection of injured CNS neurons by a single injection of a DNA plasmid encoding the Bcl-2 gene SO NEURAL PLASTICITY AND REGENERATION SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 8th International Symposium on Neural Regeneration CY DEC 08-12, 1999 CL ASILOMAR CONF CTR, PACIFIC GROVE, CALIFORNIA SP US Dept Vet Affairs, Med Res Serv, Paralyzed Vet Amer, Spin Cord Res Fdn, NINDS, Christopher Reeve Paralysis Fdn, Eastern Paralyzed Vet Assoc HO ASILOMAR CONF CTR ID CLARKES NUCLEUS NEURONS; RETINAL GANGLION-CELLS; SPINAL-CORD; TRANSGENIC MICE; ADULT-RAT; AXONAL REGENERATION; IN-VIVO; DEATH; APOPTOSIS; RESCUE C1 MCP Hahnemann Univ, Dept Anat & Neurobiol, Philadelphia, PA 19129 USA. Calif State Univ Los Angeles, Dept Biol & Microbiol, Los Angeles, CA 90032 USA. VA Med Ctr, Philadelphia, PA USA. RP Saavedra, RA (reprint author), NINDS, Ctr Neurosci, NIH, Suite 3208,6001 Execut Blvd, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS24707] NR 30 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50209-2 J9 PROG BRAIN RES PY 2000 VL 128 BP 365 EP 372 PG 8 WC Neurosciences SC Neurosciences & Neurology GA BS30B UT WOS:000169388600031 PM 11105694 ER PT J AU Steigleman, A Hertle, RW Jain, A Caruso, RC AF Steigleman, A Hertle, RW Jain, A Caruso, RC TI Optic nerve and cortical atrophy in a patient with hyper-IgM syndrome SO NEURO-OPHTHALMOLOGY LA English DT Article DE hyper-IgM syndrome; optic nerve atrophy; cortical atrophy ID X-LINKED IMMUNODEFICIENCY; CD40 AB A case of a 7-year-old male with X-linked hyper-IgM syndrome who developed cerebellar cortical atrophy and optic nerve atrophy following a brief febrile illness is discussed. After an episode of gastroenteritis, he experienced cognitive deterioration, progressive ataxia, dysarthria, cerebellar eye signs, and bilateral optic nerve atrophy that stabilized after seven months. Although we believe that he had direct neural infection, extensive microbiologic, immunologic, and radiologic investigations failed to identify a definite etiology to explain his neurologic abnormalities. This is, to our knowledge, the first reported neuro-ophthalmic disease associated with the hyper-IgM syndrome. C1 NEI, Pediat Ophthalmol Strabismus & Eye Movement Serv, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA. NEI, Natl Naval Med Ctr, NIH, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD USA. RP Hertle, RW (reprint author), NEI, Pediat Ophthalmol Strabismus & Eye Movement Serv, Lab Sensorimotor Res, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0165-8107 J9 NEURO-OPHTHALMOLOGY JI Neuro-Ophthalmol. PY 2000 VL 23 IS 1 BP 43 EP 47 PG 5 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 310QM UT WOS:000086838900007 ER PT S AU Rothman, RB Partilla, JS Dersch, CM Carroll, FI Rice, KC Baumann, MH AF Rothman, RB Partilla, JS Dersch, CM Carroll, FI Rice, KC Baumann, MH BE Ali, SF TI Methamphetamine dependence: Medication development efforts based on the dual deficit model of stimulant addiction SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID BIOGENIC-AMINE TRANSPORTERS; MESOLIMBIC DOPAMINE; REUPTAKE INHIBITORS; COCAINE WITHDRAWAL; RHESUS-MONKEYS; FENFLURAMINE; AMPHETAMINE; PHENTERMINE; SEROTONIN; RATS AB Converging lines of evidence indicate that withdrawal from prolonged exposure to stimulants and alcohol results in synaptic deficits of both dopamine (DA) and serotonin (5-HT). According to the dual deficit model proposed by the authors, DA dysfunction during cocaine or alcohol withdrawal underlies anhedonia and psychomotor retardation, whereas 5-HT dysfunction gives rise to depressed mood, obsessional thoughts, and lack of impulse control. This model predicts that pharmacotherapies which correct only one of the two neurochemical deficits will not be effective. On the other hand, pharmacotherapies which "correct" both of the proposed DA and 5-HT abnormalities should be effective in treating stimulant and alcohol dependence. This paper reviews two approaches, based on the dual deficit model, taken by our laboratory to develop medications to treat stimulant abuse. C1 NIDA, Clin Psyhcopharmacol Sect, Intramural Res Program, DIR,NIH, Baltimore, MD 21224 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Rothman, RB (reprint author), NIDA, Clin Psyhcopharmacol Sect, Intramural Res Program, DIR,NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 38 TC 13 Z9 13 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 71 EP 81 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100008 PM 11085310 ER PT S AU Cadet, JL Ordonez, S AF Cadet, JL Ordonez, S BE Ali, SF TI Serum withdrawal potentiates the toxic effects of methamphetamine in vitro SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID DISMUTASE TRANSGENIC MICE; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; FREE-RADICALS; DOPAMINERGIC NEUROTOXICITY; NEURONAL DEATH; APOPTOSIS; AMPHETAMINES; ATTENUATION; MELATONIN AB Methamphetamine (METH) has been shown to cause neurotoxic damage both in vitro and in vivo. The mechanisms of action are thought to involve the production of pathophysiologic concentration of free radicals. The present study was undertaken to assess the toxic effects of METH caused dose-dependent increased production of reactive oxygen species (ROS) and cell death. Cell death caused by METH was characterized by cytoplasmic vacuolar formation, shrinkage of cytoplasm and nuclear dissolution. Flow cytometric evaluation also revealed that this toxin causes changes similar to those observed in cells undergoing apoptosis. When taken together these observations suggest the METH can cause these cells to die Aa apoptosis. Further experiments indicated that growth of these cells in low (1 %) serum or in the absence of serum markedly enhanced the apoptotic effects of METH. These data provide further support for the ideas that METH can cause ROS-mediated apoptosis. C1 NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 26 TC 3 Z9 4 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 82 EP 91 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100009 PM 11085311 ER PT S AU Baumann, MH Ayestas, MA Dersch, CM Partilla, JS Rothman, RB AF Baumann, MH Ayestas, MA Dersch, CM Partilla, JS Rothman, RB BE Ali, SF TI Serotonin transporters, serotonin release, and the mechanism of fenfluramine neurotoxicity SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID INCREASES EXTRACELLULAR SEROTONIN; PRIMARY PULMONARY-HYPERTENSION; BIOGENIC-AMINE TRANSPORTERS; PARA-CHLOROAMPHETAMINE; RAT-BRAIN; M-CHLOROPHENYLPIPERAZINE; P-CHLOROAMPHETAMINE; META-CHLOROPHENYLPIPERAZINE; UPTAKE INHIBITION; INDAN ANALOGS AB Administration of dl-fenfluramine (FEN), or the more active isomer d-fenfluramine (dFEN), causes long-term depletion of forebrain serotonin (5-HT) in animals. The mechanism underlying FEN-induced 5-HT depletion is not known, but appears to involve 5-HT transporters (SERTs) in the brain. Some investigators have postulated that 5-HT release evoked by FEN is responsible for the deleterious effects of the drug. In the present work, we sought to examine the relationship between drug-induced 5-HT release and long-term 5-HT depletion. The acute 5-HT-releasing effects of dFEN and the non-amphetamine 5-HT agonist 1-(m-chlorophenyl)piperazine (mCPP) were evaluated using in vivo microdialysis in rat nucleus accumbens. The ability of dFEN and mCPP to interact with SERTs was assessed using in vitro assays for [-H-3]-transmitter uptake and release in rat forebrain synaptosomes. Drugs were subsequently tested for potential long-lasting effects on brain tissue 5-HT after repeated dosing (2.7 or 8.1 mg/kg, ip X 4). dFEN and mCPP were essentially equipotent in their ability to stimulate acute 5-HT release in vivo and in vitro. Both drugs produced very selective effects on 5-HT with minimal effects on dopamine. Interestingly, when dFEN or mCPP was administered repeatedly, only dFEN caused long-term 5-HT depletion in the forebrain at 2 weeks later. These data suggest that acute 5-HT release per se does not mediate the longterm 5-HT depletion associated with dFEN. We hypothesize that dFEN and other amphetamine-type releasers gain entrance into 5-HT neurons via interaction with SERTs. Once internalized in nerve terminals, drugs accumulate to high concentrations, causing damage to cells. The relevance of this hypothesis for explaining clinical side effects of FEN and dFEN, such as cardiac valvulopathy and primary pulmonary hypertension, warrants further study. C1 NIDA, Med Dev Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Baumann, MH (reprint author), NIDA, Med Dev Res Branch, Intramural Res Program, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 60 TC 16 Z9 17 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 172 EP 186 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100017 PM 11085319 ER PT S AU Baumann, MH Pablo, JP Ali, SF Rothman, RB Mash, DC AF Baumann, MH Pablo, JP Ali, SF Rothman, RB Mash, DC BE Ali, SF TI Noribogaine (12-hydroxyibogamine): A biologically active metabolite of the antiaddictive drug ibogaine SO NEUROBIOLOGICAL MECHANISMS OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Neurobiological Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY AUG 04-06, 1999 CL COPENHAGEN, DENMARK SP Int Soc Neurochem, Neuroresearch, Sevier Amer, Bie & Berntsen AS, Parke Davis, Neurosci Res Div, USDA, Natl Ctr Toxicol Res ID INDUCED LOCOMOTOR-ACTIVITY; ANTI-ADDICTIVE DRUG; NUCLEUS-ACCUMBENS; RADIOLIGAND-BINDING; ALKALOID IBOGAINE; RATS; MORPHINE; SEROTONIN; MECHANISMS; DOPAMINE AB lbogaine (IBO) is a plant-derived alkaloid that is being evaluated as a possible medication for substance use disorders. When administered peripherally to monkeys and humans, IBO is rapidly converted to an o-demethylated metabolite, 12-hydroxyibogamine (NORIBO). We have found in rats that peak blood levels of NORIBO can exceed those of the parent compound, and NORIBO persists in the bloodstream for at least 24 h. Surprisingly few studies have examined the in vivo biological activity of NORIBO. In the present series of experiments, we compared the effects of intravenous (iv) administration of IBO and NORIBO (1 and 10 mg/kg) on unconditioned behaviors, circulating stress hormones, and extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of male rats. IBO caused dose-related increases in tremors and forepaw treading, whereas NORIBO did not. Both IBO and NORIBO produced significant elevations in plasma corticosterone and prolactin, but IBO was more potent as a stimulator of corticosterone secretion. Neither drug affected extracellular DA levels in the nucleus accumbens. However, both IBO and NORIBO increased extracellular 5-HT levels, and NORIBO was more potent in this regard. The present data demonstrate that NORIBO is biologically active and undoubtedly contributes to the in vivo pharmacological profile of IBO in rats. Most importantly, NORIBO appears less likely to produce the adverse effects associated with IBO (i.e., tremors and stress-axis activation), suggesting that the metabolite may be a safer alternative for medication development. C1 NIDA, IRP, Clin Psychopharmacol Sect, NIH, Baltimore, MD 21224 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Baumann, MH (reprint author), NIDA, IRP, Clin Psychopharmacol Sect, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 15 Z9 16 U1 1 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-279-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 914 BP 354 EP 368 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BT09R UT WOS:000171939100033 PM 11085335 ER PT J AU Launer, LJ Ross, GW Petrovitch, H Masaki, K Foley, D White, LR Havlik, RJ AF Launer, LJ Ross, GW Petrovitch, H Masaki, K Foley, D White, LR Havlik, RJ TI Midlife blood pressure and dementia: the Honolulu-Asia aging study SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; vascular dementia; blood pressure; cardiovascular disease; epidemiology; longitudinal study; elderly; middle age adults ID CORONARY HEART-DISEASE; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; COGNITIVE DECLINE; APOLIPOPROTEIN-E; JAPANESE MEN; RISK-FACTORS; HYPERTENSION; STROKE; ATHEROSCLEROSIS AB We studied the association of mid-life blood pressure to late age dementia, specifically Alzheimer's disease and vascular dementia. Data are from the cohort of 3703 Japanese-American men who were followed in the Honolulu Heart Program (HHP,1965-l971), and subsequently re-examined in 1991 for dementia. We assessed the risk (odds ratio (95% CI)) for dementia associated with categories of systolic (SBP) and diastolic blood pressure (DBP), stratified by never/ever treatment with anti-hypertensive medications, and adjusting for age, education, apolipoprotein epsilon allele, smoking and alcohol intake. Among those never treated (57% sample), the risk for dementia was OR 95%CI 3.8 (1.6-8.7) for DBP of 90-94 mmHg, and 4.3 (1.7-10.8) for DBP of 95 mmHg and over compared to those with DBP of 80 to 89 mmHg. Compared to those with SEP of 110 to 139 mmHg, the risk for dementia was 4.8 (2.0-11.0) in those with SEP 160 mmHg and higher. Blood pressure was not associated with the risk for dementia in treated men. These results were consistent for Alzheimer's disease and vascular dementia. This study suggests elevated levels of blood pressure in middle age can increase the risk for late age dementia in men never treated with anti-hypertensive medication. (C) 2000 Published by Elsevier Science Inc. All rights reserved. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs, Honolulu, HI USA. Univ Hawaii, Sch Med, Honolulu Heart Program, Kuakini Med Ctr, Honolulu, HI 96822 USA. Univ Hawaii, Sch Med, Dept Med, Honolulu, HI 96822 USA. RP Launer, LJ (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, Gateway Bldg 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HR-02901]; NIA NIH HHS [N01-AG-42149] NR 42 TC 492 Z9 501 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN-FEB PY 2000 VL 21 IS 1 BP 49 EP 55 DI 10.1016/S0197-4580(00)00096-8 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 312FA UT WOS:000086931500007 PM 10794848 ER PT J AU Petrovitch, H White, LR Izmirilian, G Ross, GW Havlik, RJ Markesbery, W Nelson, J Davis, DG Hardman, J Foley, DJ Launer, LJ AF Petrovitch, H White, LR Izmirilian, G Ross, GW Havlik, RJ Markesbery, W Nelson, J Davis, DG Hardman, J Foley, DJ Launer, LJ TI Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS SO NEUROBIOLOGY OF AGING LA English DT Article DE population-based longitudinal study; hypertension; Alzheimer's disease; neuropathology ID PROGRESSIVE SUPRANUCLEAR PALSY; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; CEREBRAL ATROPHY; APOLIPOPROTEIN-E; NONDEMENTED INDIVIDUALS; CLINICAL-DIAGNOSIS; HYPERTENSION; HEALTH; ASSOCIATION AB Midlife hypertension is associated with later development of cognitive impairment, vascular dementia (VsD), and possibly Alzheimer's disease (AD). Neuropathic cerebrovascular lesions and brain atrophy have been associated with elevated blood pressure (BP), however, to our knowledge there have been no prospective investigations of an association of blood pressure levels measured in midlife with the microscopic lesions of AD. The investigated the relationship of BP level in midlife to development of neurofibrillary tangles (NFT), neuritic plaques (WP), and low brain weight at autopsy among Japanese-American men who were members of the Honolulu Heart Program/Honolulu-Asia aging Study (HHP/HAAS) cohort. The HHP/HAAS is a population-based, longitudinal study of cognitive function and dementia with 36 years of follow-up. Neocortical and hippocampal NFT and NP were counted per mm(2) and fixed brain weight was measured for 243 decedents. Elevated systolic BP, (greater than or equal to 160 mm Hg) in midlife was associated with low brain weight and greater numbers of NP in both neocortex and hippocampus. Diastolic BP elevation, (greater than or equal to 95 mm Hg) was associated with greater numbers of NFT in hippocampus. Results indicate that in addition to the accepted association of high BP with neuropathic cerebrovascular lesions, there is a direct relationship with brain atrophy, NP and NFT. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Kuakini Med Ctr, Honolulu Asia Aging Study, Honolulu, HI 96813 USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Univ Hawaii, John A Burns Sch Med, Dept Pathol, Honolulu, HI 96822 USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs, Honolulu, HI USA. Louisiana State Univ, Dept Pathol, New Orleans, LA USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY USA. Univ Kentucky, Dept Pathol & Lab Med, Lexington, KY 40506 USA. RP Petrovitch, H (reprint author), Kuakini Med Ctr, Honolulu Asia Aging Study, Suite 307,846 S Hotel St, Honolulu, HI 96813 USA. FU NHLBI NIH HHS [N01-HC-O5102]; NIA NIH HHS [1-PO1-AGO5119, N01-AG-4-2149] NR 38 TC 239 Z9 240 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JAN-FEB PY 2000 VL 21 IS 1 BP 57 EP 62 DI 10.1016/S0197-4580(00)82479-3 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 312FA UT WOS:000086931500008 PM 10794849 ER PT J AU Longstreth, WT Arnold, AM Manolio, TA Burke, GL Bryan, N Jungreis, CA O'Leary, D Enright, PL Fried, L AF Longstreth, WT Arnold, AM Manolio, TA Burke, GL Bryan, N Jungreis, CA O'Leary, D Enright, PL Fried, L CA Cardiovasc Hlth Study Collaborativ TI Clinical correlates of ventricular and sulcal size on cranial magnetic resonance imaging of 3,301 elderly people - The cardiovascular health study SO NEUROEPIDEMIOLOGY LA English DT Article DE magnetic resonance imaging; aged; cognition; hypertension ID ESTROGEN-REPLACEMENT THERAPY; MINI-MENTAL STATE; ALZHEIMERS-DISEASE; OLDER ADULTS; BRAIN; ABNORMALITIES; RISK; MR; HYPERTENSION; PERFORMANCE AB To identify potential risk factors for and clinical manifestations of ventricular and sulcal enlargement on cranial magnetic resonance imaging (MRI), 3,301 community-dwelling people 65 years or older without a history of stroke or transient ischemic attack underwent extensive standardized evaluations and MRI. In the multivariate model, increased age and white matter grade on MRI were the dominant risk factors for ventricular and sulcal grade. For ventricular grade, other than race, for which non-Blacks had higher grades, models for men and women shared no other factors. For sulcal grades, models for men and women shared variables reflecting cigarette smoking and diabetes. Clinical features were correlated more strongly with ventricular than sulcal grade and more strongly for women than men. Significant age-adjusted correlations between ventricular grade and the Digit-Symbol Substitution Test were found for men and women. Prospective studies will be needed to extend findings of this cross-sectional analysis. Copyright (C) 2000 S. Karger AG. Basel. C1 Univ Washington, Dept Neurol & Epidemiol, Seattle, WA 98104 USA. Univ Washington, Dept Biostat, Seattle, WA 98104 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Pittsburgh, Med Ctr, Dept Radiol, Neuroradiol Div, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Neurol Surg, Neuroradiol Div, Pittsburgh, PA USA. Tufts Univ, New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. Univ Arizona, Resp Sci Ctr, Tucson, AZ 85721 USA. RP Longstreth, WT (reprint author), Univ Washington, Harborview Med Ctr, Dept Neurol, Box 359775,325 9th Ave, Seattle, WA 98104 USA. FU NHLBI NIH HHS [N01-HC-85086, N01-HC-85079, N01-HC-95103] NR 27 TC 93 Z9 94 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD JAN-FEB PY 2000 VL 19 IS 1 BP 30 EP 42 DI 10.1159/000026235 PG 13 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 269KJ UT WOS:000084475700004 PM 10654286 ER PT S AU Sternberg, EM AF Sternberg, EM BE Conti, A Maestroni, GJM McCann, SM Sternberg, EM Lipton, JM Smith, CC TI Does stress make you sick and belief make you well? The science connecting body and mind SO NEUROIMMUNOMODULATION: PERSPECTIVES AT THE NEW MILLENNIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Congress of the International-Society-for-Neuroimmunomodulation CY SEP 29-OCT 02, 1999 CL LUGANO, SWITZERLAND SP State Canton Ticino, Dept Educ, Univ Insubria, Med Sch, Swiss Canc League, Lega Ticinese Lotta Contro Cancro C1 NIMH, CNE, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, CNE, NIH, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-287-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 917 BP 1 EP 3 PG 3 WC Immunology; Multidisciplinary Sciences; Clinical Neurology SC Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09U UT WOS:000171939400001 PM 11268334 ER PT S AU Rogers, TJ Steele, AD Howard, OMZ Oppenheim, JJ AF Rogers, TJ Steele, AD Howard, OMZ Oppenheim, JJ BE Conti, A Maestroni, GJM McCann, SM Sternberg, EM Lipton, JM Smith, CC TI Bidirectional heterologous desensitization of opioid and chemokine receptors SO NEUROIMMUNOMODULATION: PERSPECTIVES AT THE NEW MILLENNIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Congress of the International-Society-for-Neuroimmunomodulation CY SEP 29-OCT 02, 1999 CL LUGANO, SWITZERLAND SP State Canton Ticino, Dept Educ, Univ Insubria, Med Sch, Swiss Canc League, Lega Ticinese Lotta Contro Cancro ID PROTEIN-KINASE-C; PERIPHERAL-BLOOD; MET-ENKEPHALIN; PHAGOCYTIC FUNCTIONS; MONONUCLEAR-CELLS; ANTIBODY-RESPONSE; INTERFERON-GAMMA; BETA-ENDORPHIN; MORPHINE; CHEMOTAXIS AB Opioids are known to suppress a number of elements of the immune response, including antimicrobial resistance, antibody production, and delayed-type hypersensitivity. Phagocytic cells may be particularly susceptible to opioid administration, since reduced production of the cytokines IL-1, IL-6 and TNF-alpha, monocyte-mediated phagocytosis, and both neutrophil and monocyte chemotaxis have all been well established. Earlier studies have shown that both mu- and delta -opioid agonists induce a chemotactic response in monocytes and neutrophils. In addition, mu- and delta -opioid administration inhibited the chemotactic response of these cell populations to a number of chemokines through a process of heterologous desensitization. We report here that mu-, delta-, and kappa -opioid agonists also induce a chemotactic response in T lymphocytes. Using the human T-cell line Jurkat, we have confirmed previous observations that pre-incubation with met-enkephalin (MetEnk), an endogenous opioid agonist, prevents the subsequent chemotactic response to the chemokine RANTES. On the other hand, treatment with MetEnk does not alter the response to the chemokine SDF-1 alpha. Moreover, we found that pretreatment with RANTES prevented a subsequent response of monocytes to the mu -opioid agonist DAMGO. These results suggest that activation of members of the opioid and chemokine receptor families leads to downregulation of each other's leukocyte migratory activities. C1 Temple Univ, Sch Med, Dept Microbiol & Immunol, Ctr Subst Abuse Res, Philadelphia, PA 19140 USA. Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Rogers, TJ (reprint author), Temple Univ, Sch Med, Dept Microbiol & Immunol, Ctr Subst Abuse Res, 3400 N Broad St, Philadelphia, PA 19140 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU NIDA NIH HHS [DA-06650, DA-11130] NR 51 TC 63 Z9 67 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-287-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 917 BP 19 EP 28 PG 10 WC Immunology; Multidisciplinary Sciences; Clinical Neurology SC Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09U UT WOS:000171939400003 PM 11268344 ER PT S AU Chrousos, GP AF Chrousos, GP BE Conti, A Maestroni, GJM McCann, SM Sternberg, EM Lipton, JM Smith, CC TI The stress response and immune function: Clinical implications - The 1999 Novera H. Spector Lecture SO NEUROIMMUNOMODULATION: PERSPECTIVES AT THE NEW MILLENNIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Congress of the International-Society-for-Neuroimmunomodulation CY SEP 29-OCT 02, 1999 CL LUGANO, SWITZERLAND SP State Canton Ticino, Dept Educ, Univ Insubria, Med Sch, Swiss Canc League, Lega Ticinese Lotta Contro Cancro ID PITUITARY-ADRENAL AXIS; RECEPTOR ANTAGONIST; DAYTIME SLEEPINESS; INTERLEUKIN-6; CYTOKINES; HORMONES; INFLAMMATION; DISORDERS; FATIGUE; DISEASE C1 NICHHD, Pediat Endocrinol Sect, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NICHHD, Pediat Endocrinol Sect, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10-9D42, Bethesda, MD 20892 USA. NR 24 TC 104 Z9 108 U1 0 U2 8 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-287-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 917 BP 38 EP 67 PG 30 WC Immunology; Multidisciplinary Sciences; Clinical Neurology SC Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09U UT WOS:000171939400005 PM 11268364 ER PT S AU Elenkov, IJ Chrousos, GP Wilder, RL AF Elenkov, IJ Chrousos, GP Wilder, RL BE Conti, A Maestroni, GJM McCann, SM Sternberg, EM Lipton, JM Smith, CC TI Neuroendocrine regulation of IL-12 and TNF-alpha/IL-10 balance - Clinical implications SO NEUROIMMUNOMODULATION: PERSPECTIVES AT THE NEW MILLENNIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Congress of the International-Society-for-Neuroimmunomodulation CY SEP 29-OCT 02, 1999 CL LUGANO, SWITZERLAND SP State Canton Ticino, Dept Educ, Univ Insubria, Med Sch, Swiss Canc League, Lega Ticinese Lotta Contro Cancro ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR-ALPHA; HUMAN-MONOCYTES; GENE-EXPRESSION; INTERLEUKIN-10 LEVELS; CYTOKINE PRODUCTION; CD4(+) LYMPHOCYTES; MONONUCLEAR-CELLS; ADENOSINE RELEASE; IGE PRODUCTION AB Interleukin-12 and tumor necrosis factor (TNF)-alpha promote T-helper (Th) I responses and cellular immunity, whereas IL-10 suppresses Th1 activities and stimulates Th2 and humoral immune responses. Recent evidence indicates that glucocorticoids, norepinephrine, epinephrine, histamine, and adenosine inhibit the production of human IL-12 and TNF-alpha, whereas they do not affect or even stimulate the production of IL-10. Through this mechanism these neuroendocrine mediators may cause a selective suppression of Th1 responses and a Th2 shift rather than generalized Th suppression. The substantial Th2-driving force of endogenous stress mediators, as well as histamine and adenosine, can be amplified to a great extent during certain conditions and may play a role in increased susceptibility of the organism to various infections that are normally cleared by Th1 responses. In addition, conditions that contribute to a substantial increase or decrease of local or systemic concentrations of these mediators via modulation of IL-12, TNF alpha /IL-10 balance may also play a role in induction, expression, and progression of certain autoimmune diseases, allergic/atopic reactions, and tumor growth. These conditions include: acute or chronic stress; cessation of chronic stress or chronic hypoactivity of the stress system; severe exercise; serious surgical procedures or traumatic injuries; major burns, severe ischemia or hypoxia; pregnancy and the postpartum period. Thus, better understanding of the neuroendocrine regulation of IL-12, TNF-alpha /IL-10 balance might help the development of new therapeutic strategies for the treatment of Th1- and Th2-mediated human diseases. C1 NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Elenkov, IJ (reprint author), NICHHD, PREB, Pediat Endocrinol Sect, NIH, Bldg 10,Room 9D42,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. EM elenkovi@mail.nih.gov NR 59 TC 90 Z9 90 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-287-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 917 BP 94 EP 105 PG 12 WC Immunology; Multidisciplinary Sciences; Clinical Neurology SC Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09U UT WOS:000171939400008 PM 11268424 ER PT S AU Wilder, RL Griffiths, MM Cannon, GW Caspi, R Remmers, EF AF Wilder, RL Griffiths, MM Cannon, GW Caspi, R Remmers, EF BE Conti, A Maestroni, GJM McCann, SM Sternberg, EM Lipton, JM Smith, CC TI Susceptibility to autoimmune disease and drug addiction in inbred rats - Are there mechanistic factors in common related to abnormalities in hypothalamic-pituitary-adrenal axis and stress response function? SO NEUROIMMUNOMODULATION: PERSPECTIVES AT THE NEW MILLENNIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Congress of the International-Society-for-Neuroimmunomodulation CY SEP 29-OCT 02, 1999 CL LUGANO, SWITZERLAND SP State Canton Ticino, Dept Educ, Univ Insubria, Med Sch, Swiss Canc League, Lega Ticinese Lotta Contro Cancro ID CORTICOTROPIN-RELEASING HORMONE; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; COLLAGEN-INDUCED ARTHRITIS; CONDITIONED PLACE PREFERENCE; ADJUVANT-INDUCED ARTHRITIS; QUANTITATIVE TRAIT LOCUS; VENTRAL TEGMENTAL AREA; CENTRAL-NERVOUS-SYSTEM; WALL-INDUCED ARTHRITIS; BROWN-NORWAY RAT AB DA and LEW inbred rats are extraordinarily susceptible to a wide range of experimental autoimmune diseases. These diseases include rheumatoid arthritis models such as collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA), multiple sclerosis models such as myelin-basic-protein (MBP)-induced experimental autoimmune encephalomyelitis (MBP-EAE), and autoimmune uveitis models such as retinal S antigen (SAG) and interphotoreceptor-retinoid-binding-protein (IRBP) -induced experimental autoimmune uveitis (SAG-EAU and IRBP-EAU, respectively). DA and LEW rats are also addiction-prone to various drugs of abuse, such as cocaine. Moreover, they exhibit a variety of behavioral and biochemical characteristics that appear to be related to their susceptibility to addiction. By contrast, F344 and BN rats show quite different phenotypes. They are relatively resistant to CIA, AIA, MBP-EAE, SAG-EAU, and IRBP-EAU, and they are relatively resistant to addiction. Interestingly, both DA and LEW rats, in contrast to F344 and BN rats, have abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function. For example, circadian production of corticosteroids is very abnormal in DA and LEW rats; that is, they exhibit minimal circadian variation in corticosterone levels. Since corticosteroids potentially have significant influences on immune function and autoimmune disease susceptibility and may also influence sensitivity to drugs of abuse, we have begun to dissect genetic control of these various phenotypic differences, focusing initially on the regulation of autoimmune disease expression. Using genomewide scanning techniques involving F2 crosses of DA X F344 (CIA and AIA), DA X BN (CIA), and LEW X F344 [IRBP-EAU and streptococcal-cell-wall arthritis (SCWA)], we have identified, to date, 14 genomic regions [quantitative trait loci (QTL)] that regulate disease expression in these crosses. Development and analysis of QTL-congenic rats involving these loci are in progress and should permit us to address the relationships among autoimmune disease susceptibility, drug addiction, and HPA axis and stress response function. These initial data, however, indicate that the genetic control of the autoimmune disease traits is highly complex. C1 NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Utah, Vet Affairs Med Ctr, Sch Med, Dept Med,Res Serv, Salt Lake City, UT 84132 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Wilder, RL (reprint author), NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N240, Bethesda, MD 20892 USA. NR 78 TC 20 Z9 20 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-287-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 917 BP 784 EP 796 PG 13 WC Immunology; Multidisciplinary Sciences; Clinical Neurology SC Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09U UT WOS:000171939400078 PM 11268408 ER PT S AU Jafarian-Tehrani, M Sternberg, EM AF Jafarian-Tehrani, M Sternberg, EM BE Conti, A Maestroni, GJM McCann, SM Sternberg, EM Lipton, JM Smith, CC TI Neuroendocrine and other factors in the regulation of inflammation - Animal models SO NEUROIMMUNOMODULATION: PERSPECTIVES AT THE NEW MILLENNIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Congress of the International-Society-for-Neuroimmunomodulation CY SEP 29-OCT 02, 1999 CL LUGANO, SWITZERLAND SP State Canton Ticino, Dept Educ, Univ Insubria, Med Sch, Swiss Canc League, Lega Ticinese Lotta Contro Cancro ID SYMPATHETIC NERVOUS-SYSTEM; PITUITARY-ADRENAL AXIS; INDUCED ARTHRITIS; AUTOIMMUNE-DISEASES; LEWIS RATS; SUSCEPTIBILITY; STRESS; LOCI; IDENTIFICATION; COMMUNICATION AB A variety of animal models have been used to study the role of neuroendocrine responses in various aspects of autoimmune/inflammatory disease. Complex models of autoimmune disease, such as inflammatory arthritis in rats and thyroiditis in chickens, indicate a role for blunted HPA axis and dysregulated sympathoneuronal responses in susceptibility to autoimmune disease. A variety of approaches including pharmacological, surgical (ablation, transplantation), genetic linkage and segregation studies have been used to identify factors contributing to the phenotypes of susceptibility or resistance to inflammatory/autoimmune disease. Innate inflammation, or the earliest nonspecific form of the inflammatory response, which is characterized by fluid exudation and migration of immune cells to inflammatory sites, is a subtrait of these forms of inflammatory disease. Genetic linkage and segregation studies in inflammatory susceptible and resistant rat strains indicate that this subtrait is multigenic and polygenic; that is, that multiple loci on multiple chromosomes, each with a weak effect, control this trait, and that there is a large environmental component to the variability of this trait. Such information derived from animal studies can be used to target candidate genes for further study and to inform the design of human studies. C1 NIMH, Integrat Neural Immune Program, CNE, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Integrat Neural Immune Program, CNE, NIH, Bldg 10 Rm 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 32 TC 6 Z9 6 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-287-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 917 BP 819 EP 824 PG 6 WC Immunology; Multidisciplinary Sciences; Clinical Neurology SC Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09U UT WOS:000171939400081 PM 11268411 ER PT S AU Chikanza, IC Petrou, P Chrousos, G AF Chikanza, IC Petrou, P Chrousos, G BE Conti, A Maestroni, GJM McCann, SM Sternberg, EM Lipton, JM Smith, CC TI Perturbations of arginine vasopressin secretion during inflammatory stress - Pathophysiologic implications SO NEUROIMMUNOMODULATION: PERSPECTIVES AT THE NEW MILLENNIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 4th International Congress of the International-Society-for-Neuroimmunomodulation CY SEP 29-OCT 02, 1999 CL LUGANO, SWITZERLAND SP State Canton Ticino, Dept Educ, Univ Insubria, Med Sch, Swiss Canc League, Lega Ticinese Lotta Contro Cancro ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; LEWIS RATS; SUBSTANCE-P; GLUCOCORTICOID RECEPTOR; AUTOIMMUNE-DISEASE; IMMUNE-RESPONSES AB Pro-inflammatory cytokines, such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha), released from inflammatory foci, can activate the hypothalamus to produce corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP). These hypothalamic peptides in synergy increase ACTH production by the pituitary gland and hence corticosteroid (CS) secretion by the adrenal cortices. CS dampens inflammation. The pituitary also produces prolactin (PRL), which is proinflammatory, and macrophage inhibitory factor (MIF), which by counteracting the anti-inflammatory and immunosuppressive effects of CS, is pro-inflammatory. Lewis rats develop a variety of induced-autoimmune inflammatory conditions, such as streptococcal cell wall arthritis, whereas the histocompatible F344 Fisher rats are resistant to this condition. Lewis rats have a defective hypothalamic-pituitary adrenal (HPA) response to a variety of hypothalamic stimuli, but have augmented systemic secretion of AVP. Patients with rheumatoid arthritis (RA) have deficient CS with exaggerated PRL responses to inflammatory stimuli. Within inflammatory foci, CRH is pro-inflammatory. AVP, which augments autologous mixed lymphocyte reactions, can replace the IL-2 requirement for gamma IFN production by T cells via V-1a receptors and potentiates primary antibody responses, is also pro-inflammatory. Lewis rats have significantly high plasma levels, hypothalamic content, and in vitro release of AVP in comparison to the inflammatory disease-resistant Fischer rats. Immunoneutralization of AVP attenuates inflammatory responses. In Sprague-Dawley rats, AVP potentiates PRL secretion. Preliminary studies in patients with RA have shown that the circulating levels of AVP are significantly increased, which might be a compensatory response to low CS levels or a result of elevated levels of IL-6 in these patients but could nevertheless contribute to rheumatoid inflammation. A similar observation has been made in patients with ankylosing spondylitis. C1 St Bartholomews & Royal London Sch Med & Dent, Bone & Joint Res Unit, London EC1 6BQ, England. Appolon Hosp, Rheumatol Clin, Nicosia, Cyprus. NICHHD, Endocrinol Sect, Bethesda, MD 20892 USA. RP Chikanza, IC (reprint author), St Bartholomews & Royal London Hosp, Sch Med & Dent, Bone & Joint Res Unit, New Sci Bldg,Charterhouse Sq, London EC1M 6BQ, England. RI chen, xuanlan/H-4158-2011 NR 89 TC 44 Z9 44 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-287-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 917 BP 825 EP 834 PG 10 WC Immunology; Multidisciplinary Sciences; Clinical Neurology SC Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BT09U UT WOS:000171939400082 PM 11268412 ER PT J AU Ryu, SY Jeong, KS Yoon, WK Park, SJ Kang, BN Kim, SH Park, BK Cho, SW AF Ryu, SY Jeong, KS Yoon, WK Park, SJ Kang, BN Kim, SH Park, BK Cho, SW TI Somatostatin and substance P induced in vivo by lipopolysaccharide and in peritoneal macrophages stimulated with lipopolysaccharide or interferon-gamma have differential effects on murine cytokine production SO NEUROIMMUNOMODULATION LA English DT Article DE somatostatin; substance P; cytokine; macrophage ID VASOACTIVE-INTESTINAL-PEPTIDE; BLOOD MONONUCLEAR-CELLS; HUMAN-MONOCYTES; SPLEEN-CELLS; RECEPTOR; NEUROPEPTIDES; MODULATION; MOUSE; PROLIFERATION; INTERLEUKIN-6 AB We have investigated whether lipopolysaccharide (LPS) induces substance P (SP) and somatostatin (SOM) in popliteal lymph nodes in vivo and whether macrophages are a source of SP and SOM in vitro. We have also investigated the effect of SP and SOM treatment on the production of cytokines, SP reached a maximum 3 days after injection of LPS (100 mu g/footpad) and then declined. SOM expression after LPS injection reached a maximum at 5-7 days. Stimulation of thioglycolate-elicited peritoneal macrophages with LPS (20 mu g/ml), recombinant interferon-gamma (rIFN-gamma, 100 U/ml), and LPS plus rIFN-gamma induced SOM and SP. Thioglycolate-elicited, unstimulated peritoneal macrophages also synthesized these peptides, SOM (10(-12)-10(-8) M) Significantly inhibited IL-6 and IFN-gamma production, whereas SP at those concentrations enhanced cytokine production by activated lymphocytes and macrophages. These findings suggest that neuropeptides which originate from macrophages and nerve fibers act as immunomodulators to mediate changes in the pattern of cytokine production. Copyright (C) 2000 S. Karger AG, Basel. C1 Chungnam Natl Univ, Coll Vet Med, Dept Vet Med, Taejon 305764, South Korea. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. Kyungpook Natl Univ, Coll Vet Med, Taegu 702701, South Korea. Chonnam Natl Univ, Coll Vet Med, Kwangju, South Korea. RP Ryu, SY (reprint author), Chungnam Natl Univ, Coll Vet Med, Dept Vet Med, Taejon 305764, South Korea. NR 33 TC 24 Z9 25 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2000 VL 8 IS 1 BP 25 EP 30 DI 10.1159/000026449 PG 6 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 328BX UT WOS:000087829900005 PM 10859485 ER PT J AU Cohen, J Sugita, Y Chader, GJ Schwartz, JP AF Cohen, J Sugita, Y Chader, GJ Schwartz, JP TI Recombinant forms of the neurotrophic factor pigment epithelium-derived factor activate cellular metabolism and inhibit proliferation of the RAW macrophage cell line SO NEUROIMMUNOMODULATION LA English DT Article DE MTS assay; glioma growth inhibition; pigment epithelium-derived factor; urea; gliatrophic ID GROWTH-FACTOR-BETA; CEREBELLAR GRANULE CELLS; NONINHIBITORY SERPIN; COLORIMETRIC ASSAY; FACTOR PEDF; FACTOR-BETA-1; CULTURE; IDENTIFICATION; ASTROCYTES; MICROGLIA AB Recombinant forms of the neurotrophic factor pigment epithelium-derived factor (PEDF) activate metabolism of RAW macrophage cells while simultaneously inhibiting their proliferation. The recombinant forms (rPEDF) acted with EC(50)s of 0.1-1 nM while full-length native bovine PEDF was inactive. Urea, which is the buffer used to extract recombinant PEDF, stimulated RAW cell proliferation, the first report of an effect of urea on non-kidney cells. PEDF acted within 12 h and its effects persisted up to 72 h with continuous exposure. Although rPEDF had no direct action on glioma cell lines, it increased the amount of a soluble factor released by RAW cells which was capable of blocking glioma cell division. Thus PEDF may function as a neuroimmune modulator, affecting both neural and immune system cells. Copyright (C) 1999 S. Karger AG, Basel. C1 NINDS, NTFS, Mol Genet Sect, Clin Neurosci Branch,NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NINDS, NTFS, Mol Genet Sect, Clin Neurosci Branch,NIH, Bldg 36 Room 4A31, Bethesda, MD 20892 USA. NR 28 TC 7 Z9 8 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2000 VL 7 IS 1 BP 51 EP 58 DI 10.1159/000026420 PG 8 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 290JZ UT WOS:000085674300007 PM 10601819 ER PT J AU Orban, Z Mitsiades, N Burke, TR Tsokos, M Chrousos, GP AF Orban, Z Mitsiades, N Burke, TR Tsokos, M Chrousos, GP TI Caffeic acid phenethyl ester induces leukocyte apoptosis, modulates nuclear factor-kappa B and suppresses acute inflammation SO NEUROIMMUNOMODULATION LA English DT Article DE NF-kappa B; p65; apoptosis; acute inflammation; caffeic acid phenethyl ester ID SPLENIC MICROARCHITECTURE; TRANSCRIPTION FACTORS; RECEPTOR ANTAGONIST; TUMOR-CELLS; IN-VIVO; ACTIVATION; EXPRESSION; RESPONSES; DISEASE; MICE AB Nuclear factor kappa-B (NF-kappa B) is a heterodimeric transcription factor with a pivotal role in orchestrating immune and inflammatory processes, Inflammatory cytokines and prostanoids activate NF-kappa B, which, in turn, stimulates expression of cytokines, proteases, adhesion molecules and other inflammatory mediators. Caffeic acid phenethyl ester (CAPE) is a compound that modulates nuclear binding of the NF-kappa B p65 subunit (RelA). To determine whether CAPE decreases the viability of cells participating in host defense, we first tested its in vitro effect on a glucocorticoid-sensitive and -resistant cell line of lymphoid origin. CAPE induced apoptotic cell death in a dose-dependent fashion and to a similar extent in both cell lines. Furthermore, a low concentration of CAPE decreased the LD50 of dexamethasone by 3- to 5-fold. Since therapeutic induction of apoptosis of activated inflammatory cells holds the attraction of destroying effector cells safely without secondary tissue damage, we examined the effects of CAPE in a rat model of carrageenin-induced subcutaneous inflammation. Local administration of CAPE resulted in increased leukocyte apoptosis and marked reduction in exudate leukocyte, neutrophil and monocyte concentrations at the inflammatory site. CAPE decreased expression of cytosolic I kappa B alpha and increased nuclear translocation of p65. These findings may suggest that novel anti-inflammatory therapies can be based upon activation of NF-kappa B-mediated transcription of genes curbing the inflammatory response and that CAPE or its analogs hold therapeutic promise. Copyright (C) 2000 S. Karger AG, Basel. C1 NICHD, DEB, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Bethesda, MD 20892 USA. RP Orban, Z (reprint author), NICHD, DEB, Bldg 10,Room 10N262,10 Ctr Dr, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014 NR 34 TC 109 Z9 115 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2000 VL 7 IS 2 BP 99 EP 105 DI 10.1159/000026427 PG 7 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 290TM UT WOS:000085694000007 PM 10686520 ER PT J AU Lao, GF Scheuss, V Gerwin, CM Su, QN Mochida, S Rettig, J Sheng, ZH AF Lao, GF Scheuss, V Gerwin, CM Su, QN Mochida, S Rettig, J Sheng, ZH TI Syntaphilin: A syntaxin-1 clamp that controls SNARE assembly SO NEURON LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; RAT HIPPOCAMPAL-NEURONS; TRANSMITTER RELEASE; MEMBRANE-FUSION; NEUROTRANSMITTER RELEASE; ADAPTER PROTEINS; CALCIUM CHANNELS; COMPLEX; SYNAPTOTAGMIN; SYNAPSES AB Syntaxin-1 is a key component of the synaptic vesicle docking/fusion machinery that forms the SNARE complex with VAMP/synaptobrevin and SNAP-25. Identifying proteins that modulate SNARE complex formation is critical for understanding the molecular mechanisms underlying neurotransmitter release and its modulation. We have cloned and characterized a protein called syntaphilin that is selectively expressed in brain. Syntaphilin competes with SNAP-25 for binding to syntaxin-1 and inhibits SNARE complex formation by absorbing free syntaxin-1. Transient overexpression of syntaphilin in cultured hippocampal neurons significantly reduces neurotransmitter release. Furthermore, introduction of syntaphilin into presynaptic superior cervical ganglion neurons in culture inhibits synaptic transmission. These findings suggest that syntaphilin may function as a molecular clamp that controls free syntaxin-1 availability for the assembly of the SNARE complex, and thereby regulates synaptic vesicle exocytosis. C1 NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. Max Planck Inst Biophys Chem, Dept Membrane Biophys, D-37077 Gottingen, Germany. Tokyo Med Univ, Dept Physiol, Tokyo 1608402, Japan. RP Sheng, ZH (reprint author), NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. RI Rettig, Jens/K-5103-2013; Volker, Scheuss/G-7846-2015 OI Rettig, Jens/0000-0001-6160-3954; NR 50 TC 68 Z9 74 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN PY 2000 VL 25 IS 1 BP 191 EP 201 DI 10.1016/S0896-6273(00)80882-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 279KP UT WOS:000085043200021 PM 10707983 ER PT J AU Chao, CC Hu, SX Gekker, G Lokensgard, JR Heyes, MP Peterson, PK AF Chao, CC Hu, SX Gekker, G Lokensgard, JR Heyes, MP Peterson, PK TI U50,488 protection against HIV-1-related neurotoxicity: involvement of quinolinic acid suppression SO NEUROPHARMACOLOGY LA English DT Article DE HIV; neurotoxicity; N-methyl-D-aspartate receptor; opioids; quinolinate ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; CENTRAL NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; HUMAN BRAIN; HIV-1 INFECTION; CEREBRAL-ISCHEMIA; NITRIC-OXIDE; CULTURES; MACROPHAGES AB The pathogenesis of human immunodeficiency virus type 1 (HIV-1) encephalopathy has been associated with multiple factors including the neurotoxin quinolinate (an endogenous N-methyl-D-aspartate [NMDA] receptor ligand) and viral proteins. The kappa opioid receptor (KOR) agonist U50,488 recently has been shown to inhibit HIV-1 p24 antigen production in acutely infected microglial cell cultures. Using primary human brain cell cultures in the present study, we found that U50,488 also suppressed in a dose-dependent manner the neurotoxicity mediated by supernatants derived from HIV-l-infected microglia. This neuroprotective effect of U50,488 was blocked by the KOR selective antagonist nor-binaltorphimine. The neurotoxic activity of the supernatants from HIV-1-infected microglia was blocked by the NMDA receptor antagonists 2-amino-5-phosphsnovalerate and MK-801. HIV-1 infection of microglial cell cultures induced the release of quinolinate, and U50,488 dose-dependently suppressed quinolinate release by infected microglial cell cultures with a corresponding inhibition of HIV-1 p24 antigen levers. These findings suggest that the kappa opioid ligand U50,488 may have therapeutic potential in HIV-1 encephalopathy by attenuating microglial cell production of the neurotoxin quinolinate and viral proteins. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Minneapolis Med Res Fdn, Inst Brain & Immune Disorders, Minneapolis, MN USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. NIMH, Neurotoxicol Lab, Bethesda, MD 20892 USA. RP Peterson, PK (reprint author), Hennepin Cty Med Ctr, 701 Pk Ave, Minneapolis, MN 55415 USA. FU NIDA NIH HHS [DA04381, DA09924, T32-DA07239] NR 41 TC 24 Z9 24 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2000 VL 39 IS 1 BP 150 EP 160 DI 10.1016/S0028-3908(99)00063-5 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 268MG UT WOS:000084419700015 PM 10665828 ER PT J AU Wang, Y Chiang, YH Su, TP Hayashi, T Morales, M Hoffer, BJ Lin, SZ AF Wang, Y Chiang, YH Su, TP Hayashi, T Morales, M Hoffer, BJ Lin, SZ TI Vitamin D-3 attenuates cortical infarction induced by middle cerebral arterial ligation in rats SO NEUROPHARMACOLOGY LA English DT Article DE vitamin D-3; infarction; ischemia; neuroprotection; glial cell line-derived neurotrophic factor ID CELL-LINE; NEUROTROPHIC FACTOR; 1,25-DIHYDROXYVITAMIN D-3; RETINOIC ACID; 1,25(OH)(2) VITAMIN-D-3; NEUROBLASTOMA-CELLS; TOPICAL APPLICATION; STROKE INCIDENCE; NEURONAL DAMAGE; MESSENGER-RNAS AB We have previously reported that intracerebral administration of glial cell line derived neurotrophic factor (GDNF) reduces the extent of middle cerebral arterial (MCA) ligation-induced cortical infarction in rats. Recent studies have shown that application of 1,25 dihydroxyvitamin D-3 (D3) enhances GDNF mRNA expression in vitro. The purpose of the present study was to investigate if administration of D3 in vivo will protect against ischemic brain injury. Adult male Sprague-Dawley rats were injected daily with D3 or with saline for four or eight days. Animals received a 90-min right MCA ligation on the 4(th) or 8(th) day after anesthesia with chloral hydrate. Animals were sacrificed for tri-phenyl-tetrazolium chloride (TTC) staining 24 h after the onset of reperfusion. A subset of animals receiving eight days of D3 or saline treatment were used for blood gas and cerebral GDNF protein level analysis. We found that pretreatment with D3 for four days did not attenuate the ischemic injury. However, animals receiving eight days of D3 injections showed a significant reduction in the amount of infarction in the cortex. Eight day D3 treatment did not alter blood gases or blood pressure; however, it did increase calcium levels. Pretreatment with D3 significantly increased GDNF levels in the cortex. In conclusion, our data indicate that D3 reduces ischemia- induced brain damage and supports the hypothesis that this effect may be through the up-regulation of GDNF mechanisms in cortex. Published by Elsevier Science Ltd. C1 NIDA, NIH, Baltimore, MD 21224 USA. Natl Def Med Ctr, Tri Serv Gen Hosp, Taipei, Taiwan. RP Wang, Y (reprint author), NIDA, NIH, Baltimore, MD 21224 USA. RI Hayashi, Teruo/A-9690-2008 NR 44 TC 128 Z9 134 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2000 VL 39 IS 5 BP 873 EP 880 DI 10.1016/S0028-3908(99)00255-5 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 291TA UT WOS:000085751100017 PM 10699453 ER PT J AU Gasior, M Ungard, JT Beekman, M Carter, RB Witkin, JM AF Gasior, M Ungard, JT Beekman, M Carter, RB Witkin, JM TI Acute and chronic effects of the synthetic neuroactive steroid, ganaxolone, against the convulsive and lethal effects of pentylenetetrazol in seizure-kindled mice: comparison with diazepam and valproate SO NEUROPHARMACOLOGY LA English DT Article DE antiepileptic drugs; convulsions; lethality; locomotor activity; behavioral effects; epilepsy ID GABA(A) RECEPTOR; CATAMENIAL EPILEPSY; ANTIEPILEPTIC DRUGS; ANTICONVULSANT; NEUROSTEROIDS; COMPLEX; RATS; BENZODIAZEPINE; POTENTIATION; PROGESTERONE AB A high-affinity positive modulator of the GABA, receptor complex, ganaxolone, is a 3 beta-methylated analog of the naturally occurring neuroactive steroid allopregnanolone. in the present study, ganaxolone was tested for its ability to (1) suppress seizures (clonic and tonic) and lethality induced by pentylenetetrazol (PTZ) in PTZ-kindled mice (anticonvulsive effect) and (2) to attenuate the development of sensitization to the convulsive and lethal effects of PTZ in kindled mice (anti-epileptogenic effect) when given as a pretreatment prior to each PTZ injection during kindling acquisition. Two classical antiepileptic drugs, diazepam and valproate, were tested for comparison. All three drugs dose-dependently suppressed tonic seizures and lethality induced by PTZ in kindled mice; only ganaxolone was effective against clonic seizures. Ganaxolone showed anti-epileptogenic properties as it reduced the sensitivity of kindled mice to the convulsive (clonic and tonic seizures) and lethal effects of PTZ, Diazepam showed anti-epileptogenic effects against tonic seizures and lethality, but not clonic seizures; valproate was ineffective in preventing development of any of these effects. Sensitivity to PTZ-induced seizures and lethality was not affected in mice with a history of repeated treatment with ganaxolone, diazepam, or valproate. The drugs had effects on ambulatory activity that ranged from no effect (ganaxolone) through moderate impairment (diazepam) to marked disruption (valproate). Taken together, the results of the present study add to accumulating evidence of the unique anticonvulsive/behavioral profile of neuroactive steroids. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NIDA, Addict Res Ctr, Drug Dev Grp, Behav Neurosci Res Branch,NIH, Baltimore, MD 21224 USA. Univ Groningen, Ctr Pharm, Dept Med Chem, NL-9713 AW Groningen, Netherlands. CoCensys Inc, Dept Pharmacol, Irvine, CA 92618 USA. RP Gasior, M (reprint author), NIDA, Addict Res Ctr, Drug Dev Grp, Behav Neurosci Res Branch,NIH, Baltimore, MD 21224 USA. NR 37 TC 48 Z9 50 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2000 VL 39 IS 7 BP 1184 EP 1196 DI 10.1016/S0028-3908(99)00190-2 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 311KJ UT WOS:000086883100007 PM 10760361 ER PT J AU Peoples, RW Stewart, RR AF Peoples, RW Stewart, RR TI Alcohols inhibit N-methyl-D-aspartate receptors via a site exposed to the extracellular environment SO NEUROPHARMACOLOGY LA English DT Article DE NMDA; alcohol; ethanol; pentanol; ion channel; extracellular ID CEREBELLAR GRANULE CELLS; ETHANOL-INDUCED INHIBITION; LONG-TERM POTENTIATION; ACTIVATED ION CURRENT; PROTEIN-KINASE-C; NMDA RECEPTORS; HIPPOCAMPAL-NEURONS; NR1 SUBUNIT; GLYCINE RECEPTORS; ADULT-RAT AB N-Methyl-D-aspartate (NMDA) receptors are important CNS target sites of alcohols, but the site and mechanism of action of alcohols on NMDA receptors remains unclear. In CHO-K1 cells transfected with NR1/NR2B NMDA receptor subunits, ethanol inhibited NMDA-activated current with an IC50 of 138 mM. Truncation of the intracellular C-terminal domain of the NR1 subunit (NR1T) did not alter ethanol sensitivity when combined with the NR2B subunit, but a similar truncation of the NR2B subunit (NR2BT) slightly enhanced ethanol sensitivity of receptors formed from coexpression with either NR1 or NR1T subunits. 1-Pentanol applied externally inhibited NMDA receptors with an IC50 of 9.9 mM, but intracellular application of 1-pentanol (25 mM) did not alter NMDA receptor inhibition by externally applied ethanol or 1-pentanol. In addition, the amplitude of NMDA-activated current did not decrease during the time required for 1-pentanol (25 mM) to diffuse throughout the cytoplasm. Ethanol did not inhibit NMDA receptors when bath-applied in cell-attached patches or when applied to the cytoplasmic face of inside-out membrane patches. These results appear to be best explained by an action of alcohols on the NMDA receptor-channel protein, at a site located in a domain exposed to, or only accessible from, the extracellular environment. Published by Elsevier Science Ltd. C1 NIAAA, Unit Cellular Neuropharmacol, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Peoples, RW (reprint author), NIAAA, Unit Cellular Neuropharmacol, Mol & Cellular Neurobiol Lab, NIH, Pk 5 Bldg,Rm 158,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. NR 48 TC 45 Z9 45 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2000 VL 39 IS 10 BP 1681 EP 1691 DI 10.1016/S0028-3908(00)00067-8 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 339EX UT WOS:000088465600001 PM 10884550 ER PT J AU Wang, Y Chou, J Jeng, CH Morales, M Wang, JY AF Wang, Y Chou, J Jeng, CH Morales, M Wang, JY TI Chronic methamphetamine exposure decreases high affinity uptake function in norepinephrine afferents in the cerebellar cortex: an electrophysiological and electrochemical study SO NEUROPHARMACOLOGY LA English DT Article DE methamphetamine; voltammetry; electrophysiology; norepinephrine; high affinity uptake ID PURKINJE-CELL RESPONSES; RAT-BRAIN; STRIATAL DOPAMINE; UPTAKE SITES; D-AMPHETAMINE; RELEASE; POTENTIATION; NEURONS; ETHANOL; USERS AB It has been reported that chronic methamphetamine (MA) treatment decreases monoamine release in different brain regions. However, the clearance of norepinephrine (NE) after chronic MA intake is not clear. In the present study, we administered MA to Sprague-Dawley rats for I month. The animals were later anesthetized with urethane for electrophysiological recording. Previous studies have indicated that gamma-aminobutyric acid (GABA)-induced electrophysiological responses are enhanced by norepinephrine (NE) acting via postsynaptic beta-adrenergic receptors. We found that local application of the NE high affinity uptake inhibitor desmethylimipramine (DMI) significantly potentiated GABA-induced electrophysiological depressions in cerebellar Purkinje neurons in control rats. In contrast, DMI did not augment GABA responses in rats chronically treated with MA for 1 month, or in rats withdrawn from MA for 7-14 days after a I-month MA treatment. To further examine if DMI-induced GABA modulation is altered by post- or pre-synaptic mechanisms in chronic MA-treated rats, we examined the electrophysiological interaction of GABA and isoproterenol (ISO), a postsynaptic beta-adrenergic receptor agonist, in Purkinje neurons. We found that GABA-induced inhibition is potentiated by local application of ISO in both control and chronic MA rats, suggesting that the reduction in DMI/GABA interactions is probably not mediated through post-synaptic noradrenergic mechanisms. Presynaptic NE clearance was further examined using in vivo chronoamperometric methods. Extracellular NE levels in the cerebellar cortex were measured using Nafion-coated carbon fiber sensors. We found that local application of DMI inhibited NE clearance in control rats, but not in chronic MA animals, suggesting that presynaptic NE clearance is reduced after chronic MA treatment. In addition, NE levels in cerebellar tissue were measured using HPLC-ECD. The NE concentration was significantly decreased in chronic MA rats. Taken together, our data suggest that regulation of uptake by DMI at central noradrenergic nerve terminals is abnormal after chronic MA exposure. Published by Elsevier Science Ltd. C1 Natl Inst Drug Abuse, Baltimore, MD 21224 USA. Natl Def Med Ctr, Taipei, Taiwan. RP Wang, Y (reprint author), Natl Inst Drug Abuse, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 42 TC 9 Z9 10 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 2000 VL 39 IS 11 BP 2112 EP 2123 DI 10.1016/S0028-3908(00)00021-6 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 350AV UT WOS:000089079100018 PM 10963754 ER PT J AU Ali, SO Denicoff, KD Altshuler, LL Hauser, P Li, XM Conrad, AJ Mirsky, AF Smith-Jackson, EE Post, RM AF Ali, SO Denicoff, KD Altshuler, LL Hauser, P Li, XM Conrad, AJ Mirsky, AF Smith-Jackson, EE Post, RM TI A preliminary study of the relation of neuropsychological performance to neuroanatomic structures in bipolar disorder SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID TEMPORAL-LOBE STRUCTURE; MAGNETIC-RESONANCE; MOOD DISORDERS; SIGNAL HYPERINTENSITIES; VENTRICULAR ENLARGEMENT; ELDERLY DEPRESSIVES; BRAIN ABNORMALITIES; COGNITIVE CHANGES; AFFECTIVE-ILLNESS; NORMATIVE DATA AB Objective: To investigate the relation between neuropsychological dysfunction and volumetric measures of neuroanatomic structures in patients with bipolar disorder; Background: Previous research suggests that neuropsychological deficits are associated with neuroanatomic changes in patients with bipolar disorder. Method: Twenty-six outpatients who met Diagnostic and Statistical Manual, Third Edition-Revised criteria for bipolar disorder were administered a battery of neuropsychological tests that assessed, memory, abstracting ability, psychomotor performance, sustained attention, and intelligence. Patients also received a magnetic resonance imaging scan, from which volumes of the temporal lobes, hippocampus, third ventricle, and areas of the lateral ventricles were calculated. Using multiple regression analyses, neuroanatomic structures were compared with neuropsychological test variables. Results: Data suggest that a larger right hippocampal volume is associated with poorer neuropsychological functioning. Conclusions: Further studies are needed to both replicate and examine the relation between potential mechanisms of neuroanatomic alterations and neuropsychological dysfunction in patients with bipolar disorder. C1 NIMH, Psychol Sect, Biol Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Sect Clin & Expt Neuropsychol, Lab Brain & Cognit, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Baltimore Vet Affairs Med Ctr, Psychiat Serv, Baltimore, MD USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Natl Inst Genet, Los Angeles, CA USA. RP Denicoff, KD (reprint author), NIMH, Psychol Sect, Biol Psychiat Branch, Bldg 10,Room 3N212,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Ali, Syed/0000-0003-3131-3299 NR 66 TC 53 Z9 54 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JAN PY 2000 VL 13 IS 1 BP 20 EP 28 PG 9 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 273BZ UT WOS:000084688500004 PM 10645733 ER PT J AU Kestler, LP Malhotra, AK Finch, C Adler, C Breier, A AF Kestler, LP Malhotra, AK Finch, C Adler, C Breier, A TI The relation between dopamine D-2 receptor density and personality: Preliminary evidence from the NEO personality inventory-revised SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; NOVELTY SEEKING; MAJOR DEPRESSION; GENE; SCHIZOPHRENIA; POLYMORPHISM; ASSOCIATION; BINDING; TRAITS AB Objective: To examine the relation between dopamine (DA) D-2 receptor-specific binding and personality, we assessed the relation between DA D-2 binding and the NEO Personality Inventory Revised (NEO PI-R). Background: Previous studies have demonstrated a relation between DA D-2 receptor-specific binding and a personality trait involving personal detachment as defined by the Karolinska Scales of Personality. A subsequent study using a different measure of personal detachment failed to replicate this finding, suggesting that metric properties of the personality scale may be important. To further examine this issue, we assessed the relation between DA D-2 binding and a third personality measure, the NEO PI-R. Methods: Eighteen adult subjects completed the NEO PI-R and participated in an C-11-raclopride positron emission tomography study to quantify striatal DA D-2 receptor binding. Results: We did not find a significant relation between binding and detachment-like traits on the NEO PI-R; however, we found a significant relation between DA D-2 receptor binding and the NEO PI-R personality facet of Depression (r = 0.75, p <0.0001). Conclusions: The results fail to replicate the findings of previous studies reporting an association between DA D-2 receptor density and personal detachment, suggesting that the relation is relatively specific to the trait defined by the Karolinska Scales of Personality. The relation between a nonclinical personality trait of depression and DA D-2 binding, if replicated, may help to elucidate the role of dopamine in depression. C1 NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. Hillside Hosp, Unit Mol Psychiat, Glen Oaks, NY 11004 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Kestler, LP (reprint author), Emory Univ, 202 Psychol Bldg, Atlanta, GA 30322 USA. NR 34 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JAN PY 2000 VL 13 IS 1 BP 48 EP 52 PG 5 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 273BZ UT WOS:000084688500007 PM 10645736 ER PT J AU King, DE Herning, RI Gorelick, DA Cadet, JL AF King, DE Herning, RI Gorelick, DA Cadet, JL TI Gender differences in the EEG of abstinent cocaine abusers SO NEUROPSYCHOBIOLOGY LA English DT Article DE cocaine; EEG; gender differences ID DEPENDENT PATIENTS; QUANTITATIVE EEG; ALCOHOL; TECHNETIUM-99M-HMPAO; WITHDRAWAL; PERFUSION; INSOMNIA; SAMPLE; USERS AB Gender differences in the EEG were explored in cocaine-abusing individuals not seeking treatment. Twenty currently abstinent cocaine-abusing females aged 21-41 were studied. Their cocaine use history was matched to 20 currently abstinent cocaine-abusing males, Twelve female and 20 male non-drug-abusing individuals served as a control group. Resting eyes closed EEG was recorded from 8 leads, The males who used cocaine had elevated EEG beta (p < 0.0125) and reduced alpha (p < 0.0125) when compared to the cocaine-abusing females and control subjects. These findings suggest that the EEG of cocaine-abusing women may be more normal than that of cocaine-abusing men. Such gender-specific differences for cocaine-abusing populations may require gender-specific treatment to improve outcome. Copyright (C) 2000 S. Karger AG, Basel. C1 NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Herning, RI (reprint author), NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 44 TC 18 Z9 18 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 2000 VL 42 IS 2 BP 93 EP 98 DI 10.1159/000026678 PG 6 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 344WG UT WOS:000088782000007 PM 10940764 ER PT J AU Rickard, TC Romero, SG Basso, G Wharton, C Flitman, S Grafman, J AF Rickard, TC Romero, SG Basso, G Wharton, C Flitman, S Grafman, J TI The calculating brain: an fMRI study SO NEUROPSYCHOLOGIA LA English DT Article DE fMRI; math; cognition; arithmetic; number processing ID MENTAL CALCULATION; LEFT-HEMISPHERE; ACTIVATION; DYSCALCULIA; ACALCULIA; MULTIPLICATION; FACTS; PET AB To explore brain areas involved in basic numerical computation, functional magnetic imaging (fMRI) scanning was performed on college students during performance of three tasks; simple arithmetic, numerical magnitude judgment, and a perceptual-motor control task. For the arithmetic relative to the other tasks, results for all eight subjects revealed bilateral activation in Brodmann's area 44, in dorsolateral prefrontal cortex (areas 9 and 10), in inferior and superior parietal areas, and in lingual and fusiform gyri. Activation was stronger on the left for all subjects, but only at Brodmann's area 44 and the parietal cortices. No activation was observed in the arithmetic task in several other areas previously implicated for arithmetic, including the angular and supramarginal gyri and the basal ganglia. In fact, angular and supramarginal gyri were significantly deactivated by the verification task relative to both the magnitude judgment and control tasks for every subject. Areas activated by the magnitude task relative to the control were more variable, but in five subjects included bilateral inferior parietal cortex. These results confirm some existing hypotheses regarding the neural basis of numerical processes, invite revision of others, and suggest productive lines for future investigation. Published by Elsevier Science Ltd. C1 NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. Univ Colorado, Boulder, CO 80309 USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. RP Rickard, TC (reprint author), NIH, Cognit Neurosci Sect, 10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. RI Basso, Gianpaolo/A-9208-2012; OI Basso, Gianpaolo/0000-0002-6245-9402; Grafman, Jordan H./0000-0001-8645-4457 NR 42 TC 174 Z9 180 U1 5 U2 29 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2000 VL 38 IS 3 BP 325 EP 335 DI 10.1016/S0028-3932(99)00068-8 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 276MP UT WOS:000084881900009 PM 10678698 ER PT J AU Carlin, D Bonerba, J Phipps, M Alexander, G Shapiro, M Grafman, J AF Carlin, D Bonerba, J Phipps, M Alexander, G Shapiro, M Grafman, J TI Planning impairments in frontal lobe dementia and frontal lobe lesion patients SO NEUROPSYCHOLOGIA LA English DT Article DE planning; Tower of London; frontal lobe lesion; frontal lobe dementia ID TOWER-OF-LONDON; POSITRON EMISSION TOMOGRAPHY; SPATIAL WORKING-MEMORY; DYSFUNCTION; TASK; NEUROPSYCHOLOGY; CHILDREN; DEFICITS; SYSTEMS AB Patients with frontal lobe brain damage are reportedly impaired on tasks that require plan development and execution. In this study, we examined the performance of 15 patients diagnosed with frontal lobe dementia and 14 patients with focal frontal lobe lesions on the Tower of London planning task. Patients with frontal lobe dementia committed a significantly higher number of rule violations, made more moves, and demonstrated longer solution time latencies compared to their matched controls. Patients with frontal lobe lesions demonstrated significantly delayed solution times and also made more moves compared to their matched controls. Frontal lobe lesion patient performance suggests an impairment in execution-related processes, while frontal lobe dementia patients appear to be impaired in both plan development and execution. Despite these findings, the identification of a specific cognitive impairment that induces these planning problems remains elusive. Published by Elsevier Science Ltd. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. OI Phipps, Michael/0000-0001-8398-5404; Grafman, Jordan H./0000-0001-8645-4457 NR 30 TC 75 Z9 77 U1 6 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2000 VL 38 IS 5 BP 655 EP 665 DI 10.1016/S0028-3932(99)00102-5 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 291RX UT WOS:000085750800013 PM 10689042 ER PT J AU Parasuraman, R Greenwood, PM Alexander, GE AF Parasuraman, R Greenwood, PM Alexander, GE TI Alzheimer disease constricts the dynamic range of spatial attention in visual search SO NEUROPSYCHOLOGIA LA English DT Article DE Alzheimer disease; attention; aging; visual search; parietal cortex ID VISUOSPATIAL ATTENTION; FEATURE-INTEGRATION; APOLIPOPROTEIN-E; SENILE DEMENTIA; ASYMMETRIES; AGE; CONJUNCTION; DEFICIT; NEURONS; ADULTS AB A cued visual search task was used to examine the dynamic range over which spatial attention affects target identification during visual search. Precues varied in validity (valid, invalid, or neutral) and in precision (cue size) of target localization. Participants were "young-old" (65-74 years) and "old-old" (75-85 years) elderly adults and individuals in the mild stage of dementia of the Alzheimer type (DAT). For all participants. search was speeded us the precision with which a precue surrounding the location of a subsequently appearing target increased (precue size decreased). The cue size effect was evident in both feature and conjunction search. but was greatly reduced in both old-old and DAT groups compared to the young-old. However, whereas all non-demented adults showed a progressive modulation of search efficiency over the entire range of cue sizes, the dynamic range of spatial attention was restricted to the most precise cue in the DAT group. The restriction in the dynamic range of spatial attention may represent an underlying component of the impairment in perceptual and memory functioning found in early-stage DAT. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. NIA, Neurosci Lab, Bethesda, MD 20892 USA. RP Parasuraman, R (reprint author), Catholic Univ Amer, Cognit Sci Lab, 250 O Boyle Hall, Washington, DC 20064 USA. FU NIA NIH HHS [AG07569, AG12387] NR 57 TC 40 Z9 41 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2000 VL 38 IS 8 BP 1126 EP 1135 DI 10.1016/S0028-3932(00)00024-5 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 326NF UT WOS:000087741100003 PM 10838147 ER PT J AU Beauchamp, MS Haxby, JV Rosen, AC DeYoe, EA AF Beauchamp, MS Haxby, JV Rosen, AC DeYoe, EA TI A functional MRI case study of acquired cerebral dyschromatopsia SO NEUROPSYCHOLOGIA LA English DT Article DE functional neuroimaging; achromatopsia; extrastriate visual; Farnsworth-Munsell 100-Hue test ID CORTICAL COLOR-BLINDNESS; HUMAN VISUAL-CORTEX; CENTRAL ACHROMATOPSIA; STRIATE CORTEX; MACAQUE MONKEY; DISCRIMINATION; PERCEPTION; PATIENT; IMAGERY; LESIONS AB Evidence from imaging studies suggests that primary visual cortex and multiple areas in ventral occipitotemporal cortex subserve color perception in humans. To learn more about the organization of these areas, we used structural and functional MRI (fMRI) to examine a patient with damage to ventral cortex. An art professor. KC, suffered a cerebrovascular accident during heart surgery that impaired his ability to perceive color. The Farnsworth-Munsell 100-Hue test was used to assess the extent of his deficit. When tested 12 months after the lesion. KG performed worse than 95% of age-matched normals on the 100-Hue test, but well above chance. Structural and functional MRI studies were conducted 3 years after the lesion to investigate the neuroanatomical correlates of KG'ss remaining color ability. Structural MRI revealed bilateral damage to ventral occipitotemporal cortex. In young and age-matched normal controls, an fMRI version of the 100-Hue reliably activated bilateral, color-selective regions in primary visual cortex and anterior and posterior ventral cortex. In subject KG, color-selective cortex was found in bilateral primary visual cortex. In ventral cortex, no color-selective activity was observed in right ventral cortex, and only a small area of activity was observed in left anterior ventral cortex. However, significant color-selective activity was observed in posterior left ventral cortex spared by the lesion. This posterior left ventral activation was similar in extent, position, and degree of color-selectivity to the posterior left posterior activation observed in normal controls, suggesting that this focus may be the cortical substrate underlying KG's remaining color perception. Published by Elsevier Science Ltd. C1 NIMH, Sect Funct Brain Imaging, Bethesda, MD 20892 USA. Palo Alto VA Med Ctr, Aging Clin Res Ctr Study Senile Demcntia, Palo Alto, CA USA. Med Coll Wisconsin, Dept Cell Biol & Anat, Milwaukee, WI 53226 USA. RP Beauchamp, MS (reprint author), NIMH, Sect Funct Brain Imaging, 10 Ctr Dr MSC 1366,Bldg 10,Room 4C104, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY-10244]; NIMH NIH HHS [MH-51358] NR 46 TC 21 Z9 22 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2000 VL 38 IS 8 BP 1170 EP 1179 DI 10.1016/S0028-3932(00)00017-8 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 326NF UT WOS:000087741100007 PM 10838151 ER PT J AU Grant, S Contoreggi, C London, ED AF Grant, S Contoreggi, C London, ED TI Drug abusers show impaired performance in a laboratory test of decision making SO NEUROPSYCHOLOGIA LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Neuroscience CY OCT 25-30, 1997 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci ID CARD SORTING TEST; OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; GLUCOSE METABOLIC RATES; HUMAN PREFRONTAL CORTEX; PERSONALITY-DISORDERS; COCAINE ABUSERS; FRONTAL DAMAGE; LOBE; ACTIVATION AB A defining feature of drun addiction is persistent drug use despite long-term adverse consequences. This study examined the performance of drug abusers on a neuropsychological test that requires evaluation of long-term outcomes in the presence of a complex set of mixed reward/punishment contingencies (the Gambling Task). In order to control for generalized deficits related to choice and planning, subjects were also administered the Wisconsin Card Sorting Task. Thirty polysubstance abusers were compared to a comparison group of 24 subjects who did not use illicit drugs of abuse. Drug abusers performed much mure poorly on the Gambling Task (net score = 10.2+/-4.7, mean +/- s.e.m.) than controls (26.0 +/- 5.3), but did not differ from controls on the Wisconsin Card Sorting Task. The results show that drug abusers are mon likely to make maladaptive decisions in the Gambling Task that result in long-term losses exceeding short-term gains. These findings indicate that the Gambling Task may be a useful model in laboratory studies of cognitive dysfunctions associated with drug abuse. Published by Elsevier Science Ltd. C1 NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD 21224 USA. RP Grant, S (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 52 TC 359 Z9 367 U1 9 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2000 VL 38 IS 8 BP 1180 EP 1187 DI 10.1016/S0028-3932(99)00158-X PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 326NF UT WOS:000087741100008 PM 10838152 ER PT J AU Westergaard, GC Liv, C Haynie, MK Suomi, SJ AF Westergaard, GC Liv, C Haynie, MK Suomi, SJ TI A comparative study of aimed throwing by monkeys and humans SO NEUROPSYCHOLOGIA LA English DT Article DE capuchin; Cebus apella; handedness; human; laterality; motor skill; posture ID CAPUCHINS CEBUS-APELLA; HAND PREFERENCE; OVERARM THROWS; MOVEMENTS; INTELLIGENCE; POSTURE; TOOLS AB This research examined hand preference and postural characteristics of aimed throwing in capuchin monkeys and humans. We sought to directly compare the throwing performances of these primates, particularly the extent to which target distance influences hand preference, throwing posture, and throwing accuracy. For both species we found positive correlations between target distances for throwing accuracy, direction and strength of hand preference, percentage of bipedal vs tripedal throws, and percentage of overarm vs underarm throws. Throwing accuracy did not vary as a function of right vs left hand use although for monkeys throwing accuracy was positively associated with hand preference strength. We noted a sex difference among humans as males threw more accurately than did females. Between-species analysis indicated that humans exhibited greater right- vs left-hand use, greater hand preference strength, a greater relative percentage of bipedal vs tripedal throws, and a lower relative percentage of overarm vs underarm throws than did monkeys. We believe that the capuchin monkey is an informative nonhuman primate model of aimed throwing in humans and that research examining the throwing behavior of capuchins provides insight into the neurological and behavioral characteristics that underlie coordinated multi-joint movements across the primate order. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 LABS Virginia Inc, Div Res, Yemassee, SC 29945 USA. NICHHD, Lab Comparat Ethol, Poolesville, MD 20837 USA. RP Westergaard, GC (reprint author), LABS Virginia Inc, Div Res, POB 557, Yemassee, SC 29945 USA. FU NCRR NIH HHS [R24 RR09983] NR 28 TC 26 Z9 27 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2000 VL 38 IS 11 BP 1511 EP 1517 DI 10.1016/S0028-3932(00)00056-7 PG 7 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 357DY UT WOS:000089484300007 PM 10906376 ER PT J AU Elvevag, B Egan, MF Goldberg, TE AF Elvevag, B Egan, MF Goldberg, TE TI Paired-associate learning and memory interference in schizophrenia SO NEUROPSYCHOLOGIA LA English DT Article DE memory interference; list-learning; neuropsychiatry ID MILDLY DISTURBED SCHIZOPHRENICS; NEUROPSYCHOLOGICAL DEFICITS; EPISODE SCHIZOPHRENIA; AMNESIC PATIENTS; MATCHED TASKS; RECALL; RECOGNITION; DYSFUNCTION; HIPPOCAMPUS; IMPAIRMENT AB Patients with frontal lobe damage have been shown to exhibit disproportionate impairments of second list learning as a result of interference effects. Based upon the assumption that schizophrenia is associated with frontal dysfunction, we attempted to explore how various manipulations of paired-associate learning tasks would interfere with schizophrenic patients' memory performance. Patients with schizophrenia were administered four tests of paired-associate learning, in which cue and response words were manipulated to increase interference across two study lists. In two tests of paired-associate learning (AB-AC lest), cue words used in one list were repeated in a second list but were associated with different response words (e.g. lion-hunter, lion-circus). One version of this test employed moderately related word pairs and the other version employed unrelated word pairs. In the other two tests (AB-ABr test), all words used in one list were repeated in a second list but were rearranged to form new pairs. Again, one version of this test used moderately related word pairs and the other version used unrelated word pairs. We hypothesized that patients with schizophrenia would exhibit disproportionate impairment of second-list learning as a result of interference effects and that they would do especially poorly in the AB-ABr task, where the word pairs were unrelated. However, these predictions were not supported. Furthermore, it was difficult to tease apart a specific problem in list discrimination from the generally poor memory of the schizophrenic patients. We suggest that the susceptibility to these interference effects in patients with schizophrenia is not a specific problem in cognition, but rather one that is confounded by general memory problems. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Room 4S235,MSC 1379,Bldg 10, Bethesda, MD 20892 USA. NR 55 TC 25 Z9 25 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PY 2000 VL 38 IS 12 BP 1565 EP 1575 DI 10.1016/S0028-3932(00)00074-9 PG 11 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 374JV UT WOS:000165342800002 PM 11074079 ER PT J AU Bartzokis, G Lu, PH Beckson, M Rapoport, R Grant, S Wiseman, EJ London, ED AF Bartzokis, G Lu, PH Beckson, M Rapoport, R Grant, S Wiseman, EJ London, ED TI Abstinence from cocaine reduces high-risk responses on a gambling task SO NEUROPSYCHOPHARMACOLOGY LA English DT Letter ID HUMAN PREFRONTAL CORTEX; MEMORY C1 Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, Little Rock, AR USA. Greater Los Angeles VA Healthcare Syst, W Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. NIDA, Brain Imaging Ctr, Baltimore, MD USA. RP Bartzokis, G (reprint author), Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. RI Bartzokis, George/K-2409-2013 NR 5 TC 67 Z9 68 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2000 VL 22 IS 1 BP 102 EP 103 DI 10.1016/S0893-133X(99)00077-9 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 267YU UT WOS:000084387500014 PM 10633497 ER PT J AU Chefer, VI Moron, JA Hope, B Rea, W Shippenberg, TS AF Chefer, VI Moron, JA Hope, B Rea, W Shippenberg, TS TI Kappa-opioid receptor activation prevents alterations in mesocortical dopamine neurotransmission that occur during abstinence from cocaine SO NEUROSCIENCE LA English DT Article DE U-69593; sensitization; medial prefrontal cortex; microdialysis; dopamine uptake ID MEDIAL PREFRONTAL CORTEX; RAT NUCLEUS-ACCUMBENS; VENTRAL TEGMENTAL AREA; MICRODIALYSIS EXTRACTION FRACTION; INDUCED BEHAVIORAL SENSITIZATION; EXTRACELLULAR DOPAMINE; QUANTITATIVE MICRODIALYSIS; INVIVO MICRODIALYSIS; EVOKED RELEASE; TIME COURSE AB In vivo microdialysis was used to characterize basal dopamine dynamics and cocaine-evoked dopamine levels in the medial prefrontal cortex of male Sprague-Dawley rats that had previously received once daily injections of cocaine (days 1-5; 20 mg/kg, i.p.) in combination with the selective kappa-opioid receptor agonist U-69593 (days 3-5; 0.32 mg/kg, s.c.) or its vehicle. The influence of these treatments on [H-3]dopamine uptake in medial prefrontal cortex synaptosomes was also determined. Three days following the cessation of drug treatment, animals with prior history of cocaine administration exhibited enhanced psychomotor stimulation in response to a subsequent cocaine challenge. This effect was not apparent in animals that had previously received the cocaine treatment regimen in combination with the kappa-opioid receptor agonist U-69593. Cocaine challenge increased prefrontal dopamine levels in all pretreatment groups, but cocaine-pre-exposed animals had lower cocaine-evoked dopamine levels and higher basal in vivo extraction fraction, indicative of an increase in basal dopamine uptake relative to controls. Pretreatment with U-69593 prevented these effects of cocaine. Measurement of [H-3]dopamine uptake in synaptosomes revealed a significant increase in uptake three days after the cessation of cocaine treatment. No increase in uptake was observed in animals that had received the cocaine treatment regimen in combination with U-69593. These results demonstrate that the early phase of abstinence from cocaine is associated with marked alterations in medial prefrontal cortex dopamine neurotransmission and that these neuroadaptations are prevented by the activation of kappa-opioid receptors. Furthermore, they raise the possibility that mesocortical dopamine neurons may be an important neural substrate upon which kappa-opioid agonists act to prevent the development of cocaine-induced behavioral sensitization. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 NIDA, Intramural Res Program, Behav Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Chefer, VI (reprint author), NIDA, Intramural Res Program, Behav Neurosci Lab, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Moron, Jose/F-3236-2012; Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 NR 62 TC 49 Z9 50 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 101 IS 3 BP 619 EP 627 DI 10.1016/S0306-4522(00)00417-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 381QJ UT WOS:000165774200013 PM 11113311 ER PT J AU Qu, Y Eysel, UT Vandesande, F Arckens, L AF Qu, Y Eysel, UT Vandesande, F Arckens, L TI Effect of partial sensory deprivation on monoaminergic neuromodulators in striate cortex of adult cat SO NEUROSCIENCE LA English DT Article DE noradrenaline; dopamine; serotonin; activity-dependent regulation; visual cortex; neuromodulator ID METHYL-D-ASPARTATE; VISUAL CORTICAL PLASTICITY; IMMEDIATE-EARLY GENES; EXTRACELLULAR CONCENTRATIONS; DIFFERENTIAL EXPRESSION; NORADRENALINE RELEASE; DOPAMINE RELEASE; CEREBRAL-CORTEX; NERVE-TERMINALS; C-FOS AB The role of monoaminergic neuromodulators in the reorganization of cortical topography following limited sensory deprivation in the adult cat was investigated. The total concentrations of dopamine, noradrenaline, serotonin and their major metabolites were measured in the visual cortex of both normal control and experimental animals using microbore high-performance liquid chromatography coupled with electrochemical detection. The experimental animals were subjected to a binocular retinal lesion corresponding to the central 10 degrees of vision and killed two weeks post-lesion. The sensory deprivation was confirmed in area 17 by measuring immediate-early gene zif-268 messenger RNA expression. Following the retinal lesion, the total concentrations of noradrenaline and dopamine were significantly higher in the non-deprived cortex of retinal lesion cats than in the deprived cortex of retinal lesion cats and the cortex of normal animals. This pattern follows the release of the excitatory neurotransmitter glutamate under the same conditions. Serotonin levels were significantly lower in the deprived cortex, and its metabolite 5-hydroxyindole-3-acetic acid was significantly higher in the non-deprived cortex than in deprived cortex and normal cortex. From these results, we suggest that the modulation of noradrenaline, dopamine and serotonin is regulated by visual afferent activity. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Catholic Univ Louvain, Lab Neuroendocrinol & Immunol Biotechnol, B-3000 Louvain, Belgium. Ruhr Univ Bochum, Sch Med, Dept Neurophysiol, D-44770 Bochum, Germany. RP Eysel, UT (reprint author), NIA, Sect Brain Physiol & Metab, NIH, Bldg 10,Rm 6N202, Bethesda, MD 20892 USA. RI Arckens, Lutgarde/C-3822-2016 NR 51 TC 12 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 101 IS 4 BP 863 EP 868 DI 10.1016/S0306-4522(00)00441-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 385BZ UT WOS:000165982900006 PM 11113334 ER PT J AU Sabo, T Lomnitski, L Nyska, A Beni, S Maronpot, RR Shohami, E Roses, AD Michaelson, DM AF Sabo, T Lomnitski, L Nyska, A Beni, S Maronpot, RR Shohami, E Roses, AD Michaelson, DM TI Susceptibility of transgenic mice expressing human apolipoprotein E to closed head injury: The allele E3 is neuroprotective whereas E4 increases fatalities SO NEUROSCIENCE LA English DT Article DE Alzheimer's disease; animal models; apolipoprotein E3; apolipoprotein E4 ID E-DEFICIENT MICE; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; TYPE-4 ALLELE; BETA-PROTEIN; BRAIN INJURY; AMYLOID-BETA; E GENOTYPE; APOE; NEURONS AB Apolipoprotein E, the major brain lipid-binding protein, is expressed in humans as three common isoforms (E2, E3 and E4). Previous studies revealed that the allele apolipoprotein E4 is a major genetic risk factor of Alzheimer's disease and that traumatic brain injury is associated with increased risk for developing this disease. Furthermore, it has been suggested that the effects of traumatic head injury and apolipoprotein E4 in Alzheimer's disease are synergistic. To test the hypothesis that the apolipoprotein E genotype affects susceptibility to brain injury, we subjected transgenic mice, expressing either human apolipoprotein E3 or human apolipoprotein E4 on a null mouse apolipoprotein E background and apolipoprotein E-deficient knockouts, to closed head injury and compared mortality, neurological recovery and the extent of brain damage of the survivors. More than 50% of the transgenic mice expressing human apolipoprotein E4 died following closed head injury, whereas only half as many of the transgenic mice expressing human apolipoprotein E3, and of the control and apolipoprotein E-deficient mice died during this period (P < 0.02). A neurological severity score used for clinical assessment of the surviving mice up to 11 days after closed head injury revealed that the four mouse groups displayed similar severity of damage at 1 h following injury. At three and 11 days post-injury, however, the neurological severity scores of the transgenic mice expressing human apolipoprotein E3 were significantly lower than those of the other three groups whose scores were similar, indicating better recovery of the transgenic mice expressing human apolipoprotein E3. Histopathological examination of the mice performed 11 days post-injury revealed, consistent with the above neurological results, that the size of the damaged brain area of the transgenic mice expressing human apolipoprotein E3 was smaller than that of the other head-injured groups. These findings show that transgenic mice expressing human apolipoprotein E4 are more susceptible than those expressing apolipoprotein E3 to closed head injury. We suggest that this effect is due to both a protective effect of apolipoprotein E3 and an apolipoprotein E4-related pathological function. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. NIEHS, Res Triangle Pk, NC 27709 USA. Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91120 Jerusalem, Israel. Glaxo Wellcome Inc, Div Res, Res Triangle Pk, NC 27709 USA. Israel Inst Biol Res, IL-70450 Ness Ziona, Israel. RP Michaelson, DM (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. NR 54 TC 87 Z9 87 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 101 IS 4 BP 879 EP 884 DI 10.1016/S0306-4522(00)00438-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 385BZ UT WOS:000165982900008 PM 11113336 ER PT J AU Grimm, JW See, RE AF Grimm, JW See, RE TI Chronic haloperidol-induced alterations in pallidal GABA and striatal D-1-mediated dopamine turnover as measured by dual probe microdialysis in rats SO NEUROSCIENCE LA English DT Article DE antipsychotic; basal ganglia; dihydrexidine; female; GABA; tardive dyskinesia ID DIHYDREXIDINE RELEASES ACETYLCHOLINE; GLUTAMIC-ACID DECARBOXYLASE; LONG-TERM HALOPERIDOL; FREELY MOVING RATS; TARDIVE-DYSKINESIA; BASAL GANGLIA; RECEPTOR AGONISTS; SUBSTANTIA-NIGRA; BRAIN DIALYSIS; STRIATOPALLIDAL NEURONS AB Using dual probe microdialysis, assessment of extracellular neurotransmitter levels in the corpus striatum and globus pallidus was performed in ovariectomized and gonadally intact female, Sprague-Dawley rats following chronic (24 weeks) oral haloperidol administration. Vacuous chewing movements, an animal analog of orofacial dyskinesia, were also recorded at several time points during haloperidol administration and throughout the dialysis sampling session. Basal GABA levels were significantly elevated in the globus pallidus of haloperidol-treated rats compared with vehicle animals. Injection of the dopamine D-1 agonist dihydrexidine (3 mg/kg, s.c.) decreased striatal dopamine levels in both vehicle and haloperidol-treated rats, with a larger decrease seen in haloperidol-treated rats. Furthermore, dihydrexidine reduced striatal 3.4-dihydroxyphenylacetic acid and homovanillic acid levels only in haloperidol-treated rats. Gonadal status had no effect on any neurochemical measure. Vacuous chewing movements were significantly elevated in haloperidol-treated groups by the sixth week of treatment, with higher counts seen in gonadally intact rats. Vacuous chewing movements were significantly elevated above baseline in all groups following dihydrexidine, with no differential effect of prior haloperidol treatment or gonadal status. These results indicate a tonic increase in pallidal GABA levels and a hypersensitivity of D-1-mediated striatal dopamine and dopamine metabolite decreases following chronic haloperidol treatment. While not found to be correlated with neurochemical measures, the heightened vacuous chewing movements in gonadally intact vs ovariectomized rats may serve as a model of hormone-mediated differences in neuroleptic-induced oral dyskinesia. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP See, RE (reprint author), Med Univ S Carolina, Dept Physiol & Neurosci, 167 Ashley Ave, Charleston, SC 29425 USA. FU NIDCR NIH HHS [DE09678] NR 51 TC 22 Z9 22 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 100 IS 3 BP 507 EP 514 DI 10.1016/S0306-4522(00)00310-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 369JA UT WOS:000165061100008 PM 11098113 ER PT J AU Wang, T Palkovits, M Rusnak, M Mezey, E Usdin, TB AF Wang, T Palkovits, M Rusnak, M Mezey, E Usdin, TB TI Distribution of parathyroid hormone-2 receptor-like immunoreactivity and messenger RNA in the rat nervous system SO NEUROSCIENCE LA English DT Article DE immunohistochemistry; in situ hybridization; anatomical localization; neuropeptide receptor ID PTH2 RECEPTOR; RIBONUCLEIC-ACID; CYCLIC-AMP; HYPOTHALAMUS; EXPRESSION; AGONIST AB The parathyroid hormone-2 receptor is a member of the secretin family of guanine nucleotide-binding protein-coupled receptors, The human parathyroid hormone-2, receptor is activated by parathyroid hormone and a recently purified hypothalamic polypeptide, tubero-infundibular peptide of 39 residues, while the rat parathyroid hormone-2 receptor is poorly activated by parathyroid hormone and is potently activated by tubero-infundibular peptide of 39 residues. In order to provide a foundation for studies on the physiological role of the parathyroid hormone-2 receptor and tubero-infundibular peptide of 39 residues, we investigated the cellular distribution of the parathyroid hormone-2 receptor in the rat CNS using both immunohistochemistry and in situ hybridization histochemistry. The receptor is found in discrete groups of neurons in many regions. It is present in scattered small cells throughout the cerebral cortex, in small and medium-sized cells in the striatum, and is quite abundant in the septum and the midline thalamic nuclei. Its expression is high in the hypothalamus, particularly in the periventricular and arcuate nuclei. Fibers and terminals in the external zone of the median eminence, and in the superficial layers of the caudal spinal trigeminal tract and the spinal cord dorsal horn, art: strongly and dramatically labeled by a parathyroid hormone-2 receptor-selective antibody. The localization of parathyroid hormone-2 receptor suggests a role in the regulation of pituitary hormone secretion, sensory information processing and homeostatic regulation. Published by Elsevier Science Ltd. C1 NIMH, Genet Lab, Cell Biol Unit, Bethesda, MD 20892 USA. Natl Inst Neurol Dis, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), NIMH, Genet Lab, Cell Biol Unit, 36 Convent Dr,MSC4094, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 22 TC 32 Z9 32 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 100 IS 3 BP 629 EP 649 DI 10.1016/S0306-4522(00)00282-7 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 369JA UT WOS:000165061100021 PM 11098126 ER PT J AU Schwartz, WJ Carpino, A de la Iglesia, HO Baler, R Klein, DC Nakabeppu, Y Aronin, N AF Schwartz, WJ Carpino, A de la Iglesia, HO Baler, R Klein, DC Nakabeppu, Y Aronin, N TI Differential regulation of fos family genes in the ventrolateral and dorsomedial subdivisions of the rat suprachiasmatic nucleus SO NEUROSCIENCE LA English DT Article DE AP-1; circadian rhythms; fos; immediate-early genes; suprachiasmatic nucleus; vasopressin ID MAMMALIAN CIRCADIAN CLOCK; DNA-BINDING ACTIVITY; GASTRIN-RELEASING PEPTIDE; IMMEDIATE-EARLY GENE; C-FOS; INTERGENICULATE LEAFLET; PHOTIC REGULATION; MESSENGER-RNA; IN-VITRO; TRANSCRIPTION FACTORS AB Extensive studies have established that light regulates c-fos gene expression in the suprachiasmatic nucleus, the site of an endogenous circadian clock, but relatively little is known about the expression of genes structurally related to c-Sos, including fra-1, fra-2 and fosB. We analysed the photic and temporal regulation of these genes at the messenger RNA and immunoreactive protein levels in rat suprachiasmatic nucleus, and we found different expression patterns after photic stimulation and depending on location in the ventrolateral or dorsomedial subdivisions. In the ventrolateral suprachiasmatic nucleus, c-fos, fra-2 and fosB expression was stimulated after a subjective-night (but not subjective-day) light pulse. Expression of the fra-2 gene was prolonged following photic stimulation, with elevated messenger RNA and protein levels that appeared unchanged for at least a few hours beyond the c-fos peak. Unlike c-fos and fra-2, the fosB gene appeared to be expressed constitutively in the ventrolateral suprachiasmatic nucleus throughout the circadian cycle; immunohistochemical analysis suggested that Delta FosB was the protein product accounting for this constitutive expression, while FosB was induced by the subjective-night light pulse. In the dorsomedial suprachiasmatic nucleus, c-fos and fra-2 expression exhibited an endogenous circadian rhythm, with higher levels during the early subjective day, although the relative abundance was much lower than that measured after light pulses in the ventrolateral suprachiasmatic nucleus. Double-label immunohistochemistry suggested that some of the dorsomedial cells responsible for the circadian expression of c-Fos also synthesized arginine vasopressin. No evidence of suprachiasmatic nucleus fra-1 expression was found. In summary, fos family genes exhibit differences in their specific expression patterns in the suprachiasmatic nucleus, including their photic and circadian regulation in separate cell populations in the ventrolateral and dorsomedial subdivisions. The data, in combination with our previous results [Takeuchi J. et al. (1993) Neuron 11, 825-836], suggest that activator protein-1 binding sites on ventrolateral suprachiasmatic nucleus target genes are constitutively occupied by Delta FosB/JunD complexes, and that c-Fos, Fra-2, FosB and JunB compete for binding after photic stimulation. The differential regulation of fos family genes in the ventrolateral and dorsomedial suprachiasmatic nucleus suggests that their circadian function(s) and downstream target(s) are likely to be cell specific. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, Bethesda, MD 20892 USA. Kyushu Univ, Med Inst Bioregulat, Dept Biochem, Fukuoka 812, Japan. Univ Massachusetts, Sch Med, Dept Med & Cell Biol, Worcester, MA 01655 USA. RP Schwartz, WJ (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 55 Lake Ave N, Worcester, MA 01655 USA. RI Nakabeppu, Yusaku/A-8902-2011 FU NINDS NIH HHS [R01 NS24542] NR 68 TC 70 Z9 71 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 98 IS 3 BP 535 EP 547 DI 10.1016/S0306-4522(00)00140-8 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 330CL UT WOS:000087945200013 PM 10869847 ER PT J AU Kiyatkin, EA Kiyatkin, DE Rebec, GV AF Kiyatkin, EA Kiyatkin, DE Rebec, GV TI Phasic inhibition of dopamine uptake in nucleus accumbens induced by intravenous cocaine in freely behaving rats SO NEUROSCIENCE LA English DT Article DE cocaine self-administration; dopamine uptake; voltammetry; reward (euphoria); addictive behavior ID CARBON-FIBER MICROELECTRODES; REAL-TIME MEASUREMENT; IN-VIVO; MOVING RATS; EXTRACELLULAR DOPAMINE; CYCLIC VOLTAMMETRY; PREFRONTAL CORTEX; BINDING-SITES; TRANSPORTERS; RELEASE AB A new approach combining fast-scan cyclic voltammetry with iontophoretic dopamine delivery was used in freely behaving rats to evaluate the time-course of dopamine uptake inhibition in nucleus accumbens induced by intravenous cocaine at a dose (1.0 mg/kg) known to maintain self-administration behavior. Cocaine significantly increased the decay time of the dopamine response without altering its magnitude or time to peak. An increase in decay time was evident at 2 min, peaked at 6 min (+ 87%), and decreased to baseline at 18 min after a single cocaine injection. The change in decay time was similar in all rats and remained essentially the same, albeit slightly larger, for subsequent cocaine injections both within a session and over repeated sessions. The change in dopamine decay time did not correlate with cocaine-induced motor activation, which was maximal during the first minute after injection and decreased slowly over the next 20 min. Our data provide direct evidence for a phasic change in dopamine uptake induced by intravenous cocaine under behaviorally relevant conditions. The relatively slow and gradual development of dopamine uptake inhibition, which peaks at times when behaving rats self-inject cocaine, is inconsistent with the suggested role of this mechanism in the acute rewarding (euphoric) effects of self-injected cocaine, but supports its role in the activational and motivational aspects of drug-seeking and drug-taking behavior. Because intravenous cocaine enters the brain rapidly and peaks in neural tissue (1-2 min) long before it effectively inhibits dopamine uptake (6 min), it appears that some of the acute psychoemotional ("rush"), behavioral, autonomic, and neuronal effects of this drug, which are apparently resistant to dopamine receptor blockade, are mediated via rapid central or peripheral mechanisms independent of monoamine uptake. Published by Elsevier Science Ltd. C1 Indiana Univ, Dept Psychol, Program Neural Sci, Bloomington, IN 47405 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA 00335, DA 02451] NR 56 TC 49 Z9 49 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 98 IS 4 BP 729 EP 741 DI 10.1016/S0306-4522(00)00168-8 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 338NY UT WOS:000088427200012 PM 10891616 ER PT J AU Ong, WY Hu, CY Soh, YP Lim, TM Pentchev, PG Patel, SC AF Ong, WY Hu, CY Soh, YP Lim, TM Pentchev, PG Patel, SC TI Neuronal localization of sterol regulatory element binding protein-1 in the rodent and primate brain: A light and electron microscopic immunocytochemical study SO NEUROSCIENCE LA English DT Article DE SREBP-1; cholesterol; fatty acids; gene expression; neurons; Niemann-Pick type C disease ID LIPOPROTEIN RECEPTOR PROMOTER; BOUND TRANSCRIPTION FACTOR; LEUCINE ZIPPER PROTEIN; PICK C1 PROTEIN; CHOLESTEROL HOMEOSTASIS; NUCLEAR-PROTEIN; CELL-MEMBRANES; GENE; SREBP-1; BIOSYNTHESIS AB Sterol regulatory element binding proteins are membrane-bound transcription factors that activate expression of several genes controlling cellular cholesterol and fatty acid homeostasis. The present study aimed to investigate the in vivo expression of sterol regulatory element binding protein-1 in the normal rodent and primate brain, and in the brain in Niemann-Pick type C disease mice. These mutant animals have lysosomal cholesterol accumulation and progressive neurodegeneration caused by an inactivating mutation of the NPC1 gene whose protein product functions in vesicular lipid trafficking. Western blot analysis of rat hippocampal homogenates with an affinity purified rabbit polyclonal antibody directed against an internal epitope of sterol regulatory element binding protein-1 identified a major 68,000 mel. wt protein consistent with the amino-terminal, transcriptionally active fragment of sterol regulatory element binding proteins-1. Immunocytochemically, this antibody revealed dense sterol regulatory element binding protein-1 staining of nuclei and light staining of the cytoplasm of cells in the neocortex and hippocampus in the rat, mouse and monkey brain. By electron microscopy of immunogold-labeled brain sections, these densely labeled cells were found to be neurons. In contrast, normal glial cells had little or no sterol regulatory element binding protein-1 immunoreactivity even at a developmental stage (postnatal day 9) which coincides with active myelination in the rat brain. Also, in contrast to the normal mouse brain, Niemann-Pick type C mice showed reduced staining of cortical and hippocampal neuronal nuclei. Since sterol regulatory element binding protein-1 has been shown to be a transcriptional regulator of fatty acid synthesis in vivo, the current findings of a predominantly neuronal nuclear expression of the 68,000 mel. wt transcriptionally active fragment of sterol regulatory element binding protein-1 highlights the established role of phospholipid metabolites and other fatty-acid containing lipids in neuronal signal transduction and other neuronal functions. Reduced sterol regulatory element binding protein-1 expression in neurons in Niemann-Pick type C may reflect a deficiency in fatty acid synthesis that could contribute to the neuronal dysfunction in this disorder. (C) 2000 IBRO. Published by Elsevier Science Ltd. C1 VA Connecticut Healthcare Syst, Neurol Serv, Newington, CT 06111 USA. Natl Univ Singapore, Dept Anat, Singapore 119260, Singapore. Natl Univ Singapore, Dept Biol Sci, Singapore 119260, Singapore. NINDS, Sect Cellular & Mol Pathophysiol, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Patel, SC (reprint author), VA Connecticut Healthcare Syst, Neurol Serv, 555 Willard Ave, Newington, CT 06111 USA. FU NINDS NIH HHS [NS34339] NR 28 TC 26 Z9 26 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 97 IS 1 BP 143 EP 153 DI 10.1016/S0306-4522(00)00031-2 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 309DD UT WOS:000086751600014 PM 10771346 ER PT J AU Kanda, S Bishop, JF Eglitis, MA Yang, Y Mouradian, MM AF Kanda, S Bishop, JF Eglitis, MA Yang, Y Mouradian, MM TI Enhanced vulnerability to oxidative stress by alpha-synuclein mutations and C-terminal truncation SO NEUROSCIENCE LA English DT Article DE Parkinson's disease; alpha-synuclein; oxidative stress; neuron; cell death ID LEWY-BODY-DISEASE; PARKINSONS-DISEASE; NEURODEGENERATIVE DISORDERS; IN-VITRO; PROTEIN; BODIES; AGGREGATION; FILAMENTS; MUTANT; IMMUNOREACTIVITY AB alpha-Synuclein is a key component of Lewy bodies found in the brains of patients with Parkinson's disease and two point mutations in this protein, Ala53Thr and Ala30Pro, are associated with rare familial forms of the disease. Several lines of evidence suggest the involvement of oxidative stress in the pathogenesis of nigral neuronal death in Parkinson's disease. In the present work we studied the effects of changes in the alpha-synuclein sequence on the susceptibility of cells to reactive oxygen species. Human dopaminergic neuroblastoma SH-SY5Y cells were stably transduced with various isoforms of a-synuclein and their survival following exposure to hydrogen peroxide or to the dopaminergic neurotoxin MPP+ was assessed. Cells expressing the two point mutant isoforms of alpha-synuclein were significantly more vulnerable to oxidative stress, with the Ala53Thr engineered cells faring the worst. In addition, cells expressing C-terminally truncated alpha-synuclein, particularly the 1-120 residue protein, were more susceptible than control beta-galactosidase engineered cells. The present experiments indicate that point mutations and C-terminal truncation of a-synuclein exaggerate the susceptibility of dopaminergic cells to oxidative damage. Thus, these observations provide a pathogenetic link between alpha-synuclein aberrations and a putative cell death mechanism in Parkinson's disease. (C) 2000 IBRO. Published by Elsevier Science Ltd. C1 NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 28 TC 148 Z9 149 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 97 IS 2 BP 279 EP 284 DI 10.1016/S0306-4522(00)00077-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 314PK UT WOS:000087064400009 PM 10799759 ER PT J AU Liu, B Du, L Kong, LY Hudson, PM Wilson, BC Chang, RC Abel, HH Hong, JS AF Liu, B Du, L Kong, LY Hudson, PM Wilson, BC Chang, RC Abel, HH Hong, JS TI Reduction by naloxone of lipopolysaccharide-induced neurotoxicity in mouse cortical neuron-glia co-cultures SO NEUROSCIENCE LA English DT Article DE naloxone stereoisomer; microglia; mouse; cortical cultures; neuroprotection ID HUMAN-IMMUNODEFICIENCY-VIRUS; KAPPA-OPIOID RECEPTORS; BRAIN-CELL-CULTURES; NITRIC-OXIDE; INDUCED HYPERACTIVITY; ALZHEIMERS-DISEASE; MICROGLIAL CELLS; MIXED GLIA; ASTROCYTES; RESPONSES AB An inflammatory response in the CNS mediated by activation of microglia is a key event in the early stages of the development of neurodegenerative diseases. Using mouse cortical mixed glia cultures, we have previously demonstrated that the bacterial endotoxin lipopolysaccharide induces the activation of microglia and the production of proinflammatory factors. Naloxone, an opioid receptor antagonist, inhibits the lipopolysaccharide-induced activation of microglia and the production of proinflammatory factors. Using neuron-glia co-cultures, we extended our study to determine if naloxone has a neuroprotective effect against lipopolysaccharide-induced neuronal damage and analysed the underlying mechanism of action for its potential neuroprotective effect. Pretreatment of cultures with naloxone (1 mu M) followed by treatment with lipopolysaccharide significantly inhibited the lipopolysaccharide-induced production of nitric oxide and the release of tumor necrosis factor-alpha, and significantly reduced the lipopolysaccharide-induced damage to neurons. More importantly, both naloxone and its opioid-receptor ineffective enantiomer (+)-naloxone were equally effective in inhibiting the lipopolysaccharide-induced generation of proinflammatory factors and the activation of microglia, as well as in the protection of neurons. These results indicate that the neuroprotective effect of naloxone is mediated by its inhibition of microglial activity and may be unrelated to its binding to the classical opioid receptors. Published by Elsevier Science Ltd. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Liu, B (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233,MDF1-01, Res Triangle Pk, NC 27709 USA. RI Chang, Raymond Chuen-Chung/C-1107-2009; liu, Bin/A-7695-2009 OI Chang, Raymond Chuen-Chung/0000-0001-8538-7993; NR 45 TC 66 Z9 69 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 97 IS 4 BP 749 EP 756 DI 10.1016/S0306-4522(00)00057-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 324VH UT WOS:000087641700015 PM 10842020 ER PT J AU Chang, RCC Hudson, PM Wilson, BC Liu, B Abel, H Hong, JS AF Chang, RCC Hudson, PM Wilson, BC Liu, B Abel, H Hong, JS TI High concentrations of extracellular potassium enhance bacterial endotoxin lipopolysaccharide-induced neurotoxicity in glia-neuron mixed cultures SO NEUROSCIENCE LA English DT Article DE glia; potassium; microglia; nitric oxide; tumor necrosis factor-alpha; cerebral inflammation ID NITRIC-OXIDE SYNTHASE; TNF-ALPHA; MICROGLIAL ACTIVATION; SPREADING DEPRESSION; GENE-EXPRESSION; CELL-CULTURES; BRAIN; RAT; CHANNELS; INVOLVEMENT AB A sudden increase in extracellular potassium ions (K+) often occurs in cerebral ischemia and after brain trauma. This increase of extracellular K+ constitutes the basis for spreading depression across the cerebral cortex, resulting in the expansion of neuronal death after ischemic and traumatic brain injuries. Besides spreading depression, it has become clear that cerebral inflammation also is a key factor contributing to secondary brain injury in acute neurological disorders. Experiments to validate the relationship between elevated levels of extracellular K+ and inflammation have not been studied. This study aims to elucidate the roles of high concentrations of extracellular K+ in bacterial endotoxin lipopolysaccharide-induced production of inflammatory factors. Increased concentration of KCl in the medium (20 mM) significantly enhanced neurotoxicity by lipopolysaccharide in glia-neuron mixed cultures. To delineate the underlying mechanisms of increased neurotoxicity, the effects of high extracellular K+ were examined by using mixed glial cultures. KCl at 20 mM significantly enhanced nitrite, an index for nitric oxide, production by about twofold, and was pronounced from 24 to 48 h, depending on the concentration of KCl. Besides nitric oxide production of tumor necrosis factor-alpha was also enhanced. The augmentative effects of high KCl on the production of inflammatory factors were probably due to the further activation of microglia, since high KCl also enhanced the production of tumor necrosis factor-alpha in microglia-enriched cultures. The increased production of nitrite by high K+ was eliminated through use of a K+-blocker. Taken together, the results show that increases of extracellular K+ concentrations in spreading depression augment lipopolysaccharide-elicited neurotoxicity, because production of inflammatory factors such as nitric oxide and tumor necrosis factor-alpha are potentiated. Since spreading depression and cerebral inflammation are important in acute neurological disorders, the present results suggest a biochemical mechanism: elevated extracellular K+ concentrations augment glial inflammatory responses, and thus the neurotoxicity. Published by Elsevier Science Ltd. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27713 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, POB 12233 MFDF1-01, Res Triangle Pk, NC 27713 USA. RI Chang, Raymond Chuen-Chung/C-1107-2009; liu, Bin/A-7695-2009 OI Chang, Raymond Chuen-Chung/0000-0001-8538-7993; NR 35 TC 28 Z9 28 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 97 IS 4 BP 757 EP 764 DI 10.1016/S0306-4522(00)00059-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 324VH UT WOS:000087641700016 PM 10842021 ER PT J AU Quan, N Mhlanga, JDM Whiteside, MB Kristensson, K Herkenham, M AF Quan, N Mhlanga, JDM Whiteside, MB Kristensson, K Herkenham, M TI Chronic sodium salicylate treatment exacerbates brain neurodegeneration in rats infected with Trypanosoma brucei SO NEUROSCIENCE LA English DT Article DE tumor necrosis factor; interleukin-1; neurotoxicity; trypanosome; parasite; aspirin ID NF-KAPPA-B; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; T-CELL RESPONSES; AFRICAN TRYPANOSOMIASIS; ANTIINFLAMMATORY DRUGS; ALZHEIMERS-DISEASE; PROSTAGLANDIN E(2); REYES-SYNDROME; MESSENGER-RNA AB We have reported previously that axonal degeneration in specific brain regions occurs in rats infected with the parasite Trypanosoma brucei. These degenerative changes occur in spatiotemporal association with over-expression of pro-inflammatory cytokine messenger RNAs in the brain. To test how aspirin-like anti-inflammatory drugs might alter the disease process, we fed trypanosome-infected rats with 200 mg/kg of sodium salicylate (the first metabolite of aspirin) daily in their drinking water. Sodium salicylate treatment in uninfected rats did not cause any neural damage. However, sodium salicylate treatment greatly exacerbated neurodegeneration in trypanosome-infected rats, resulting in extensive terminal and neuronal cell body degeneration in the cortex, hippocampus, striatum, thalamus, and anterior olfactory nucleus. The exaggerated neurodegeneration, which occurred in late stages of infection, was temporally and somewhat spatially associated with a late-appearing enhancement of messenger RNA expression of interleukin-1 beta, interleukin-1 beta converting enzyme, tumor necrosis factor-alpha, and inhibitory factor kappa B alpha in the brain parenchyma. Restricted areas showed elevations in messenger RNA expression of interleukin-1 receptor antagonist, interleukin-6, inducible nitric oxide synthase, interferon-gamma, and inducible cyclooxygenase. The association suggests that increased production of pro-inflammatory cytokines in the brain may be an underlying mechanism for neural damage induced by the chronic sodium salicylate treatment. Furthermore, the results reveal a serious complication in using aspirin-like drugs for the treatment of trypanosome infection. Published by Elsevier Science Ltd. C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. Karolinska Inst, Dept Neurosci, Stockholm, Sweden. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, Bldg 36,Room 2D15, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 54 TC 10 Z9 12 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 96 IS 1 BP 181 EP 194 DI 10.1016/S0306-4522(99)00492-3 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 283XG UT WOS:000085300900021 PM 10683422 ER PT J AU Chiesa, N Barlow, C Wynshaw-Boris, A Strata, P Tempia, F AF Chiesa, N Barlow, C Wynshaw-Boris, A Strata, P Tempia, F TI Atm-deficient mice Purkinje cells show age-dependent defects in calcium spike bursts and calcium currents SO NEUROSCIENCE LA English DT Article DE Atm-deficient; calcium; cerebellum; mouse; Purkinje cell ID ELECTRO-PHYSIOLOGICAL PROPERTIES; MAMMALIAN CEREBELLAR SLICES; CENTRAL-NERVOUS-SYSTEM; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; DNA-DAMAGE; C-ABL; PROTEIN; NEURONS; INVITRO AB Ataxia telangiectasia in humans results from homozygous loss-of-function mutations in ATM. Neurological deterioration is the major cause of death in ataxia telangiectasia patients: in the cerebellum, mainly Purkinje cells are affected. We have generated Atm-deficient mice which display neurological abnormalities by several tests of motor function consistent with an abnormality of cerebellar function, but without histological evidence of neuronal degeneration. Here we performed a more detailed morphological analysis and an electrophysiological study on Purkinje cells from Atm-deficient mice of different ages. We found no histological or immunohistochemical abnormalities. Electrophysiology revealed no abnormalities in resting membrane potential, input resistance or anomalous rectification. In contrast, there was a significant decrease in the duration of calcium and sodium firing. The calcium deficit became significant between six to eight and 12-20 weeks of age, and appeared to be progressive. By voltage-clamp recording, we found that the firing deficits were due to a significant decrease in calcium currents, while inactivating: potassium currents seem unaffected. In other mutant mice, calcium current deficits have been shown to be related to cell death. Our experiments suggest that the electrophysiological defects displayed by Atm-deficient mice are early predegenerative lesions and may be a precursor of Purkinje cell degeneration displayed by ataxia telangiectasia patients. (C) 2000 IBRO. Published by Elsevier Science Ltd. C1 Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Turin, Dept Neurosci, I-10125 Turin, Italy. RP Tempia, F (reprint author), Univ Perugia, Inst Human Physiol, I-06126 Perugia, Italy. RI Tempia, Filippo/A-5883-2012 NR 47 TC 30 Z9 31 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 96 IS 3 BP 575 EP 583 DI 10.1016/S0306-4522(99)00581-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 298TZ UT WOS:000086156400011 PM 10717437 ER PT J AU Schutz, B Chen, L Schafer, MKH Weihe, E Eiden, LE AF Schutz, B Chen, L Schafer, MKH Weihe, E Eiden, LE TI Somatomotor neuron-specific expression of the human cholinergic gene locus in transgenic mice SO NEUROSCIENCE LA English DT Article DE acetylcholine; cholinergic gene locus; choline acetyltransferase; motorneuron; vesicular acetylcholine transporter ID VESICULAR ACETYLCHOLINE TRANSPORTER; PERIPHERAL NERVOUS-SYSTEM; ACETYLTRANSFERASE GENE; PROMOTER REGION; SYNAPTIC VESICLES; GROWTH-FACTOR; RAT; SILENCER; ORGANIZATION; LOCALIZATION AB We examined the expression pattern of the vesicular acetylcholine transporter in the mouse nervous system, using rodent-specific riboprobes and antibodies, prior to comparing it with the distribution of vesicular acetylcholine transporter expressed from a human transgene in the mouse, using riboprobes and antibodies specific for human. Endogenous vesicular acetylcholine transporter expression was high in spinal and brainstem somatomotor neurons, vagal visceromotor neurons, and postganglionic parasympathetic neurons, moderate in basal forebrain and brainstem projection neurons and striatal interneurons, and low in intestinal intrinsic neurons. Vesicular acetylcholine transporter expression in intrinsic cortical neurons was restricted to the entorhinal cortex. The sequence of the mouse cholinergic gene locus to 5.1 kb upstream of the start of transcription of the vesicular acetylcholine transporter gene was determined and compared with the corresponding region of the human gene. Cis-regulatory domains implicated previously in human or rat cholinergic gene regulation are highly conserved in mouse, indicating their probable relevance to the regulation of the mammalian cholinergic gene locus in vivo. Mouse lines were established containing a human transgene that included the vesicular acetylcholine transporter gene and sequences spanning 5 kb upstream and 1.8 kb downstream of the vesicular acetylcholine transporter open reading frame. In this transgene, the intact human vesicular acetylcholine transporter was able to act as its own reporter. This allowed elements within the vesicular acetylcholine transporter open reading frame itself, shown previously to affect transcription in vitro, to be assessed in vivo with antibodies and riboprobes that reliably distinguished between human and mouse vesicular acetylcholine transporters and their messenger RNAs. Expression of the human vesicular acetylcholine transporter was restricted to mouse cholinergic somatomotor neurons in the spinal cord and brainstem, but absent from other central and peripheral cholinergic neurons. The mouse appears to be an appropriate model for the study of the genetic regulation of the cholinergic gene locus, and the physiology and neurochemistry of the mammalian cholinergic nervous system, although differences exist in the distribution of cortical cholinergic neurons between the mouse and other mammals. The somatomotor neuron-specific expression pattern of the transgenic human vesicular acetylcholine transporter suggests a mosaic model for cholinergic gene locus regulation in separate subdivisions of the mammalian cholinergic nervous system. (C) 2000 IBRO. Published by Elsevier Science Ltd. C1 NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. Univ Marburg, Inst Anat & Cell Biol, Dept Mol Neuroimmunol, D-35033 Marburg, Germany. RP Bldg 36,Room 2A-11,9000 Rockville Pike, Bethesda, MD 20892 USA. EM eiden@codon.nih.gov OI Eiden, Lee/0000-0001-7524-944X NR 49 TC 14 Z9 14 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 96 IS 4 BP 707 EP 722 DI 10.1016/S0306-4522(99)00587-4 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 299ND UT WOS:000086204000007 PM 10727789 ER PT J AU Krasnova, IN Bychkov, ER Lioudyno, VI Zubareva, OE Dambinova, SA AF Krasnova, IN Bychkov, ER Lioudyno, VI Zubareva, OE Dambinova, SA TI Intracerebroventricular administration of substance P increases dopamine content in the brain of 6-hydroxydopamine-lesioned rats SO NEUROSCIENCE LA English DT Article DE dopamine; 6-hydroxydopamine; substance P; striatum; nucleus accumbens ID VENTRAL TEGMENTAL AREA; STRIATAL DOPAMINE; PARKINSONS-DISEASE; NUCLEUS-ACCUMBENS; TACHYKININ RECEPTORS; AMINO-ACIDS; IN-VIVO; RELEASE; NEOSTRIATUM; NEURONS AB The interactions existing between substance P- and dopamine-positive neurons, notably in the basal ganglia, suggest that substance P may have therapeutic use in treatment of Parkinson's disease characterized by impaired dopaminergic transmission. The effects of intracerebroventricularly administered substance P were tested on the levels of dopamine and its metabolites in the striatum, nucleus accumbens and frontal cortex of 6-hydroxydopamine-lesioned rats. Intracerebroventricular injection of 6-hydroxydopamine decreased the levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the brain structures under investigation. Administration of substance P in low dose (0.35 nmol/kg) had no effect on the 6-hydroxydopamine-induced reduction of the dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid contents in the brain. However, treatment with substance P in higher dose (3.5 nmol/kg) increased the concentrations of dopamine and its metabolites in the striatum, nucleus accumbens and frontal cortex relative to saline-treated group. Additionally, 6-hydroxydopamine lesions significantly increased 3,4-dihydroxyphenylacetic acid/dopamine and homovanillic acid/dopamine ratios in the striatum and nucleus accumbens. Substance P (3.5 nmol/kg) partially reversed lesion-induced increases in 3,4-dihydroxyphenylacetic acid/dopamine and homovanillic acid/dopamine ratios in the striatum, but did not alter these ratios in nucleus accumbens. To test whether substance P fragmentation is responsible for this phenomenon, substance P5-11, which is one of the main substance P fragments in rat CNS, was administered in equimolar dose. Substance P5-11 was found to have no effect on the content of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the striatum and nucleus accumbens. In the frontal cortex, substance P5-11 produced decreases in dopamine levels and increases in homovanillic acid/dopamine ratio. The results of this study suggest that substance P helps to restore dopamine deficit in the brain in an animal model of Parkinson's disease, with the positive effects being more prominent on the nigrostriatal than on the mesocorticolimbic dopaminergic system, but substance P5-11 is not responsible for this effect. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Russian Acad Sci, Inst Human Brain, Mol Neurobiol Lab, St Petersburg 197376, Russia. Russian Acad Sci, Inst Expt Med, Pavlov Dept Physiol, St Petersburg 197376, Russia. RP Krasnova, IN (reprint author), NIDA, Mol Neuropsychiat Sect, Div Intramural Res, NIH, POB 5180, Baltimore, MD 21224 USA. NR 46 TC 33 Z9 36 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 95 IS 1 BP 113 EP 117 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 262ML UT WOS:000084071000012 PM 10619467 ER PT J AU Proescholdt, MG Hutto, B Brady, LS Herkenham, M AF Proescholdt, MG Hutto, B Brady, LS Herkenham, M TI Studies of cerebrospinal fluid flow and penetration into brain following lateral ventricle and cisterna magna injections of the tracer [C-14]inulin in rat SO NEUROSCIENCE LA English DT Article DE cerebrospinal fluid; intracerebroventricular; parasynaptic communication; volume transmission; [C-14]inulin; autoradiography ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL-NERVOUS-SYSTEM; FOS MESSENGER-RNA; CIRCUMVENTRICULAR ORGANS; VOLUME TRANSMISSION; BETA-ENDORPHIN; SUPRACHIASMATIC NUCLEUS; INTERSTITIAL FLUID; RAPID DISTRIBUTION; INDUCED SEIZURES AB Parasynaptic communication, also termed volume transmission, has been suggested as an important means to mediate information transfer within the central nervous system. The purpose of the present study was to visualize by autoradiography the available channels for fluid movement within the extracellular space following injection of the inert extracellular marker [C-14]inulin into the lateral ventricle or cisterna magna. Bolus injections of 5 mu l of 1 mu Ci of [C-14]inulin were made in awake rats via chronically implanted cannulae. After survival times ranging from 5 min to 4 h, brains were processed for in vivo autoradiography. At 5 min the tracer distributed throughout the ventricles, subarachnoid spaces and cisterns "downstream" of the injection sites. Penetration into the brain from these sites was complex with preferential entry along the ventral side of the brain, especially into the hypothalamus and brainstem. By 4 h virtually the entire brain was labeled irrespective of the site of tracer application. Sustained tracer entry from subarachnoid spaces suggests that some areas act as depots to trap circulating material. This mechanism may contribute to the pattern of deep penetration at later time-points. The spatial and temporal characteristics of fluid movement throughout the brain are instructive in the interpretation of many experimental procedures involving injection of molecules into the cerebrospinal fluid (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, Bldg 36,Room 2D-15, Bethesda, MD 20892 USA. NR 67 TC 119 Z9 120 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 95 IS 2 BP 577 EP 592 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 266MK UT WOS:000084303600029 PM 10658638 ER PT J AU Tonelli, L Johren, O Hoe, KL Hauser, W Saavedra, JM AF Tonelli, L Johren, O Hoe, KL Hauser, W Saavedra, JM TI Gerbil Angiotensin II AT(1) receptors are highly expressed in the hippocampus and cerebral cortex during postnatal development SO NEUROSCIENCE LA English DT Article DE renin-Angiotensin system; brain; in situ hybridization; autoradiography; limbic system ID MESSENGER-RNA EXPRESSION; LONG-TERM POTENTIATION; RAT-BRAIN; GENE-EXPRESSION; SUBTYPES; AUTORADIOGRAPHY; CALIBRATION; PITUITARY; STANDARDS; CLONING C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. RI Johren, Olaf/G-6967-2011 NR 38 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 95 IS 4 BP 981 EP 991 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 277EL UT WOS:000084919700006 PM 10682705 ER PT J AU Tomac, AC Grinberg, A Huang, SP Nosrat, C Wang, Y Borlongan, C Lin, SZ Chiang, YH Olson, L Westphal, H Hoffer, BJ AF Tomac, AC Grinberg, A Huang, SP Nosrat, C Wang, Y Borlongan, C Lin, SZ Chiang, YH Olson, L Westphal, H Hoffer, BJ TI Glial cell line-derived neurotrophic factor receptor oil availability regulates glial cell line-derived neurotrophic factor signaling: Evidence from mice carrying one or two mutated alleles SO NEUROSCIENCE LA English DT Article DE GDNF; GFR alpha 1; ischemia; transplantation; kidney; neuroprotection ID MIDDLE CEREBRAL-ARTERY; BOLUS INTRAVENTRICULAR-INJECTION; C-RET PROTOONCOGENE; SUBSTANTIA-NIGRA; TYROSINE KINASE; NERVOUS-SYSTEM; LACKING GDNF; DOPAMINERGIC-NEURONS; SUPEROXIDE-DISMUTASE; TOPICAL APPLICATION AB Glial cell line-derived neurotrophic factor receptor alpha 1 (GFR alpha 1, also known as GDNFR-alpha) is a glycolipid-anchored membrane protein of the GFR alpha family, which binds glial cell line-derived neurotrophic factor [Jing S. er al. (1996) Cell 85, 1113-1124; Treanor J. J. et nl. (1996) Nature 382, 80-83], a survival factor for several populations of central and peripheral neurons, including midbrain dopamine neurons [Lin L. F. et nl. (1993) Science 260, 1130-1132], and mediates its ligand-induced cell response via a tyrosine kinase receptor called Ret [Takahashi M. er al. (1988) Oncogene 3, 571-578; Takahashi M. and Cooper G. M. (1987) Molec. Cell Biol, 7, 1378-1385]. In this paper, we show that mice with a null mutation of the GFRa 1 gene manifest epithelial-mesenchymal interaction deficits in kidney and severe disturbances of intestinal tract development similar to those seen with glial cell line-derived neurotrophic factor or Ret null mutations. There is a marked renal dysgenesis or agenesis and the intrinsic enteric nervous system fails completely to develop. We also show that newborn GFR alpha 1-deficient mice display no or minimal changes in dorsal root and sympathetic ganglia. This is in contrast to the deficits reported in these neuronal populations in glial cell line-derived neurotrophic factor and Ret null mutations. Mesencephalic dopaminergic neurons in the substantia nigra and ventral tegmental area appear intact at the time of birth of the mutated mice. Mice homozygous for the GFR alpha 1 null mutation die within 24h of birth because of uremia. Heterozygous animals, however, live to adulthood. There is a significantly reduced neuroprotective effect of glial cell line-derived neurotrophic factor in such heterozygous animals, compared with wild-type littermates, after cerebral ischemia. Taken together with previous data on glial cell line-derived neurotrophic factor and Ret, our results strongly suggest that GFRa 1 is the essential GFR alpha receptor for signaling in the glial cell line-derived neurotrophic factor-Ret pathway in the kidney and enteric nervous system development, and that GFR alpha 2 or GFR alpha 3 cannot substitute for the absence of GFR alpha 1. Moreover, neuroprotective actions of exogenous glial cell line-derived neurotrophic factor also require full GFR alpha 1 receptor expression. Published by Elsevier Science Ltd. C1 NIDA, NIH, Baltimore, MD 21224 USA. NIH, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. Natl Def Med Ctr, Dept Neurosurg, Taipei, Taiwan. RP Hoffer, BJ (reprint author), NIDA, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 50 TC 78 Z9 81 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2000 VL 95 IS 4 BP 1011 EP 1023 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 277EL UT WOS:000084919700009 PM 10682708 ER PT B AU Hou, J Jensen, PN Major, EO AF Hou, J Jensen, PN Major, EO BE Peterson, PK Remington, JS TI The biology and clinical consequence of JC virus infection in the human brain - Progressive multifocal leukoencephalopathy SO NEW CONCEPTS IN THE IMMUNOPATHOGENESIS OF CNS INFECTIONS LA English DT Proceedings Paper CT Conference on New Concepts in the Immunopathogenesis of CNS Infections CY OCT, 1999 CL SANTA FE, NM ID MAJOR CAPSID PROTEIN; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NERVOUS-SYSTEM DISEASE; HUMAN POLYOMAVIRUS; SIMIAN VIRUS-40; ANTIRETROVIRAL THERAPY; CEREBROSPINAL-FLUID; MOLECULAR-BIOLOGY; AIDS PATIENTS; INSECT CELLS C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Hou, J (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. NR 77 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 0-632-04528-0 PY 2000 BP 205 EP 222 PG 18 WC Immunology; Infectious Diseases; Clinical Neurology SC Immunology; Infectious Diseases; Neurosciences & Neurology GA BQ82L UT WOS:000089708800011 ER PT B AU Chesebro, B AF Chesebro, B BE Peterson, PK Remington, JS TI Transmissible spongiform encephalopathies and prion protein SO NEW CONCEPTS IN THE IMMUNOPATHOGENESIS OF CNS INFECTIONS LA English DT Proceedings Paper CT Conference on New Concepts in the Immunopathogenesis of CNS Infections CY OCT, 1999 CL SANTA FE, NM ID CREUTZFELDT-JAKOB DISEASE; PRP KNOCKOUT MICE; SCRAPIE INFECTIVITY; TRANSGENIC MICE; HAMSTER SCRAPIE; MESSENGER-RNA; VIRUS-LIKE; AGENT; SUSCEPTIBILITY; EXPRESSION C1 NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Chesebro, B (reprint author), NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 63 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 0-632-04528-0 PY 2000 BP 223 EP 235 PG 13 WC Immunology; Infectious Diseases; Clinical Neurology SC Immunology; Infectious Diseases; Neurosciences & Neurology GA BQ82L UT WOS:000089708800012 ER PT J AU Scheffel, U Horti, AG Koren, AO Ravert, HT Banta, JP Finley, PA London, ED Dannals, RF AF Scheffel, U Horti, AG Koren, AO Ravert, HT Banta, JP Finley, PA London, ED Dannals, RF TI 6-[F-18]fluoro-A-85380: An in vivo tracer for the nicotinic acetylcholine receptor SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE 6-[F-18]FA; A-85380 derivative; nicotinic acetylcholine receptor (nAChR); mouse brain distribution; radiotracer; PET ID IN-VIVO; BINDING-SITES; CEREBRAL-CORTEX; BRAIN; FLUORINE-18-FPH; SCHIZOPHRENIA; RADIOLIGAND; RADIOTRACER; EPIBATIDINE; AFFINITY AB 6-[F-18]Fluoro-3-(2(S)-azetidinylmethoxy (6-[F-18]fluoro-A-85380 or 6-[F-18]FA), a new tracer for positron emission tomography, was synthesized by no-carrier-added [F-18] fluorination of 6-iodo-3-((1-tert-butoxycarbonyl-2 (S)-azetidinyl)methoxy)pyridine followed by acidic deprotection. 6-[F-18]FA followed the regional densities of brain nicotinic acetylcholine receptors (nAChRs) reported in the literature. Evidence of binding to nAChRs and high specificity of the binding in vivo was demonstrated by inhibition with nAChR selective ligands as well as with unlabeled 6-FA. A preliminary toxicology study of the 6-FA showed a relatively low biological effect. NUCL MED BIOL 27;1:51-56, 2000. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Johns Hopkins Med Inst, Div Nucl Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Div Radiat Hlth Sci, Baltimore, MD 21205 USA. NIDA, Brain Imaging Ctr, Intramural Res Program, Baltimore, MD USA. CTI Inc, Knoxville, TN USA. RP Dannals, RF (reprint author), Johns Hopkins Med Inst, Div Nucl Med, 615 N Wolfe St, Baltimore, MD 21205 USA. NR 32 TC 30 Z9 33 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2000 VL 27 IS 1 BP 51 EP 56 DI 10.1016/S0969-8051(99)00082-7 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 288NY UT WOS:000085570900006 PM 10755645 ER PT J AU Chappell, LL Dadachova, E Milenic, DE Garmestani, K Wu, CC Brechbiel, MW AF Chappell, LL Dadachova, E Milenic, DE Garmestani, K Wu, CC Brechbiel, MW TI Synthesis, characterization, and evaluation of a novel bifunctional chelating agent for the lead isotopes Pb-203 and Pb-212 SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE macrocycles; lead-203; radioimmunoconjugate; radioimmunoimaging; radioimmunotherapy ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; RADIOIMMUNOTHERAPY; COMPLEXES; STABILITY; B72.3; CARCINOMA; CLEAVAGE; CANCER; SM-153; DOTA AB Radioisotopes of Pb(II) have been of some interest in radioimmunotherapy and radioimmunoimaging (RII). However, the absence of a kinetically stable bifunctional chelating agent for Pb(II) has hampered its use for these applications. Pb-203 (T-1/2 = 52.02 h) has application potential in RII, with a gamma-emission that is ideal for single photon emission computerized tomography, whereas Pb-212 (T-1/2 = 10 h) is a source of highly cytotoxic alpha-particles via its decay to its Bi-212 (T-1/2 = 60 min) daughter. The synthesis of the novel bifunctional chelating agent 2-(4-isothiocyanotobenzyl)-1,4,7,10-tetraaza-1,4,7,10-tetra-(2-carbamoyl methyl)-cyclododecane (4-NCS-Bz-TCMC) is reported herein. The Pb[TCMC](2+) complex was less labile to metal ion release than Pb[DOTA](2-) at pH 3. and below in isotopic exchange experiments. In addition to increased stability to Pb2+ ion release at low pH, the bifunctional TCMC ligand was found to have many other advantages over the bifunctional 1,4,7,10-tetraazacyclodocane-1,4,7,10-tetraacetic acid (DOTA) ligand, These include a shorter and more straightforward synthetic route, a more efficient conjugation reaction to a monoclonal antibody (mAb), with a higher chelate to protein ratio, a higher percent immuroreactivity, and a more efficient radiolabeling reaction of the mAb-ligand conjugate with Pb-203. NUCL MED BIOL 27;1:93-100, 2000. Published by Elsevier Science Inc. C1 NIH, Radioimmune & Inorgan Chem Sect, ROB, DCS, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, DBS, NIH, Bethesda, MD 20892 USA. Rel Tek Inc, Rockville, MD USA. RP Brechbiel, MW (reprint author), NIH, Radioimmune & Inorgan Chem Sect, ROB, DCS, 10 Ctr Dr,Bldg 10,Room B3 B69, Bethesda, MD 20892 USA. RI Dadachova, Ekaterina/I-7838-2013 NR 39 TC 56 Z9 56 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2000 VL 27 IS 1 BP 93 EP 100 DI 10.1016/S0969-8051(99)00086-4 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 288NY UT WOS:000085570900013 PM 10755652 ER PT J AU Baxevanis, AD AF Baxevanis, AD TI The Molecular Biology Database Collection: an online compilation of relevant database resources SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The Molecular Biology Database Collection represents an effort geared at making molecular biology database resources more accessible to biologists. This online resource, available at http://www.oup.co.uk/nar/Volume_28/Issue_01/html/gkd115_gml.html, is intended to serve as a searchable, up-to-date, centralized jumping-off point to individual Web sites. An emphasis has also been placed on including databases where new value is added to the underlying data by virtue of curation, new data connections, or other innovative approaches. C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bldg 49,Room 4A-22, Bethesda, MD 20892 USA. NR 2 TC 32 Z9 36 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 1 EP 7 DI 10.1093/nar/28.1.1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300001 PM 10592167 ER PT J AU Wheeler, DL Chappey, C Lash, AE Leipe, DD Madden, TL Schuler, GD Tatusova, TA Rapp, BA AF Wheeler, DL Chappey, C Lash, AE Leipe, DD Madden, TL Schuler, GD Tatusova, TA Rapp, BA TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN GENES; MAP AB In addition to maintaining the GenBank(R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI) provides data analysis and retrieval and resources that operate on the data in GenBank and a variety of other biological data made available through NCBI's Web site. NCBI data retrieval resources include Entrez, PubMed, LocusLink and the Taxonomy Browser, Data analysis resources include BLAST, Electronic PCR, OrfFinder, RefSeq, UniGene, Database of Single Nucleotide Polymorphisms (dbSNP), Human Genome Sequencing pages, GeneMap'99, Davis Human-Mouse Homology Map, Cancer Chromosome Aberration Project (CCAP) pages, Entrez Genomes, Clusters of Orthologous Groups (COGs) database, Retroviral Genotyping Tools, Cancer Genome Anatomy Project (CGAP) pages, SAGEmap, Online Mendelian Inheritance in Man (OMIM) and the Molecular Modeling Database (MMDB), Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of the resources can be accessed through the NCBI home page at: http://www.ncbi.nlm.nih.gov. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Rapp, BA (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. OI Lash, Alex/0000-0003-3787-1590 NR 22 TC 327 Z9 344 U1 1 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 10 EP 14 DI 10.1093/nar/28.1.10 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300003 PM 10592169 ER PT J AU Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Rapp, BA Wheeler, DL AF Benson, DA Karsch-Mizrachi, I Lipman, DJ Ostell, J Rapp, BA Wheeler, DL TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSED SEQUENCE TAGS; DATABASE AB The GenBank(R) sequence database incorporates publicly available DNA sequences of >55 000 different organisms, primarily through direct submission of sequence data from individual laboratories and large-scale sequencing projects. Most submissions are made using the Banklt (Web) or Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping and protein structure information, plus the biomedical literature via PubMed. Sequence similarity searching is provided by the BLAST family of programs. Complete bimonthly releases and daily updates of the GenBank database are available by FTP, NCBI also offers a wide range of WWW retrieval and analysis services based on GenBank data. The GenBank data-base and related resources are freely accessible via the NCBI home page at http://www.ncbi.nlm.nih.gov. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Benson, DA (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 15 TC 682 Z9 710 U1 0 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 15 EP 18 DI 10.1093/nar/28.1.15 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300004 PM 10592170 ER PT J AU Tatusov, RL Galperin, MY Natale, DA Koonin, EV AF Tatusov, RL Galperin, MY Natale, DA Koonin, EV TI The COG database: a tool for genome-scale analysis of protein functions and evolution SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SEQUENCE; FAMILIES AB Rational classification of proteins encoded sequenced genomes is critical for making the genome sequences maximally useful for functional and evolutionary studies, The database of Clusters of Orthologous Groups of proteins (COGs) is an attempt on a phylogenetic classification of the proteins encoded in 21 complete genomes of bacteria, archaea and eukaryotes (http://www.ncbi.nlm.nih.gov/COG), The COGs were constructed by applying the criterion of consistency of genome-specific best hits to the results of an exhaustive comparison of all protein sequences from these genomes, The database comprises 2091 COGs that include 56-83% of the gene products from each of the complete bacterial and archaeal genomes and similar to 35% of those from the yeast Saccharomyces cerevisiae genome. The COG database is accompanied by the COGNITOR program that is used to fit new proteins into the COGs and can be applied to functional and phylogenetic annotation of newly sequenced genomes. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 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 NR 13 TC 1288 Z9 1340 U1 8 U2 72 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 33 EP 36 DI 10.1093/nar/28.1.33 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300009 PM 10592175 ER PT J AU Ploger, R Zhang, J Bassett, D Reeves, R Hieter, P Boguski, M Spencer, F AF Ploger, R Zhang, J Bassett, D Reeves, R Hieter, P Boguski, M Spencer, F TI XREFdb: cross-referencing the genetics and genes of mammals and model organisms SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSED SEQUENCE TAGS; DATABASE AB XREFdb supports the investigation of protein function in the context of information available through work in multiple organisms. In addition to facilitating the association of functional data among known genes from multiple organisms, XREFdb has developed strategies that provide access to information associated with as-yet unstudied genes. The database organizes protein similarity and genetic map positional information from diverse sources in the public domain to facilitate investigator evaluation of potential functional significance. XREFdb is found at URL www.ncbi.nlm.nih. gov/XREFdb. C1 Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. Rosetta Inpharmat, Kirkland, WA USA. Univ British Columbia, Ctr Mol Med, Vancouver, BC V5Z 1M9, Canada. RP Spencer, F (reprint author), Johns Hopkins Univ, Sch Med, Inst Med Genet, Ross 1167-720 Rutland Ave, Baltimore, MD 21205 USA. FU NHGRI NIH HHS [HG00971] NR 13 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 120 EP 122 DI 10.1093/nar/28.1.120 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300032 PM 10592198 ER PT J AU Maglott, DR Katz, KS Sicotte, H Pruitt, KD AF Maglott, DR Katz, KS Sicotte, H Pruitt, KD TI NCBI's LocusLink and RefSeq SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE AB The NCBI has introduced two new web resources-LocusLink and RefSeq-that facilitate retrieval of gene-based information and provide reference sequence standards. These resources are designed to provide a non-redundant view of current knowledge about human genes, transcripts and proteins. Additional information about these resources is available on the LocusLink web site at http://www. ncbi.nlm.nih.gov/Locuslink/. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Pruitt, KD (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 8 TC 113 Z9 118 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 126 EP 128 DI 10.1093/nar/28.1.126 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300034 PM 10592200 ER PT J AU Pesole, G Liuni, S Grillo, G Licciulli, F Larizza, A Makalowski, W Saccone, C AF Pesole, G Liuni, S Grillo, G Licciulli, F Larizza, A Makalowski, W Saccone, C TI UTRdb and UTRsite: specialized databases of sequences and functional elements of 5 ' and 3 ' untranslated regions of eukaryotic mRNAs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MESSENGER-RNA DEGRADATION; GENE-EXPRESSION; TRANSLATIONAL REGULATION; 3'-UNTRANSLATED REGION; PROTEIN INTERACTIONS; BINDING-PROTEINS; IRON-METABOLISM; CIS-ELEMENT; SELENOCYSTEINE; LOCALIZATION AB The-5' and 3' untranslated regions of eukaryotic mRNAs may play a crucial role in the regulation of gene expression controlling mRNA localization, stability and translational efficiency. For this reason we developed UTRdb, a specialized database of 5' end 3' untranslated sequences of eukaryotic mRNAs cleaned from redundancy. UTRdb entries are enriched with specialized information not present in the primary databases including the presence of nucleotide sequence patterns already demonstrated by experimental analysis to have some functional role. All these patterns have been collected in the UTRsite database so that it is possible to search any input sequence for the presence of annotated functional motifs, Furthermore, UTRdb entries have been annotated for the presence of repetitive elements. All internet resources implemented for retrieval and functional analysis of 5' and 3' untranslated regions of eukaryotic mRNAs are accessible at http://bigarea.area.ba.cnr. it:8000/EmbIT/UTRHome/. C1 Univ Milan, Dipartimento Fisiol & Biochim Gen, I-20133 Milan, Italy. CNR, Area Ric Bari, I-70126 Bari, Italy. CNR, Ctr Studio Mitocondri & Metab Energet, I-70126 Bari, Italy. Univ Bari, Dipartmento Biochim & Biol Mol, I-70126 Bari, Italy. NIH, NLM, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Pesole, G (reprint author), Univ Milan, Dipartimento Fisiol & Biochim Gen, Via Celoria 26, I-20133 Milan, Italy. RI Pesole, Graziano/C-1408-2009; Pesole, Graziano/E-9051-2014; Licciulli, Flavio/B-8984-2015; Makalowski, Wojciech/I-2843-2016; Grillo, Giorgio/F-7617-2015 OI Pesole, Graziano/0000-0003-3663-0859; Pesole, Graziano/0000-0003-3663-0859; Licciulli, Flavio/0000-0002-1861-8947; Grillo, Giorgio/0000-0002-0137-5811 NR 38 TC 62 Z9 63 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 193 EP 196 DI 10.1093/nar/28.1.193 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300057 PM 10592223 ER PT J AU Wang, YL Addess, KJ Geer, L Madej, T Marchler-Bauer, A Zimmerman, D Bryant, SH AF Wang, YL Addess, KJ Geer, L Madej, T Marchler-Bauer, A Zimmerman, D Bryant, SH TI MMDB: 3D structure data in Entrez SO NUCLEIC ACIDS RESEARCH LA English DT Article AB Three-dimensional structures are now known for roughly half of all protein families. It is thus quite likely, in searching sequence databases, that one will encounter a homolog with known structure and be able to use this information to infer structure-function properties. The goal of Entrez's 3D structure database is to make this information accessible and useful to molecular biologists, To this end, Entrez's search engine provides three powerful features: (i) Links between databases; one may search by term matching in Medline(R), for example, and link to 3D structures reported in these articles, (ii) Sequence and structure neighbors; one may select all sequences similar to one of interest, for example, and link to any known 3D structures, (iii) Sequence and structure visualization; identifying a homolog with known structure, one may view a combined molecular-graphic and alignment display, to infer approximate 3D structure. Entrez's MMDB (Molecular Modeling DataBase) may be accessed at: http://www.ncbi.nlm.nih.gov/Entrez/structure.html. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RI Marchler-Bauer, Aron/A-9681-2009; Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 NR 9 TC 32 Z9 34 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 243 EP 245 DI 10.1093/nar/28.1.243 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300070 PM 10592236 ER PT J AU Sullivan, SA Aravind, L Makalowska, I Baxevanis, AD Landsman, D AF Sullivan, SA Aravind, L Makalowska, I Baxevanis, AD Landsman, D TI The Histone Database: a comprehensive WWW resource for histones and histone fold-containing proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING; NUCLEOSOME CORE; CHROMATIN; RESOLUTION; VARIETY; OCTAMER; MOTIF AB The Histone Database (HDB) is an annotated and searchable collection of all full-length sequences and structures of histone and non-histone proteins containing the histone fold motif. These sequences are both eukaryotic and archaeal in origin. Several new histone fold-containing proteins have been identified, including Spt7p, and a few false positives have been removed from the earlier version of HDB. Database contents include compilations of post-translational modifications for each of the core and linker histones, as well as genomic information in the form of map loci for the human histone gene complement, with the genetic loci linked to Online Mendelian Inheritance in Man (OMIM). Conflicts between similar sequence entries from a number of source databases are also documented. Newly added to the HDB are multiple sequence alignments in which predicted functions of histone fold amino acid residues are annotated. The database is freely accessible through the WWW at http://genome.nhgri.nih.gov/histones/. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Landsman, D (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A Room 8N805, Bethesda, MD 20894 USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 24 TC 24 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 320 EP 322 DI 10.1093/nar/28.1.320 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300094 PM 10592260 ER PT J AU Banerjee-Basu, S Ryan, JF Baxevanis, AD AF Banerjee-Basu, S Ryan, JF Baxevanis, AD TI The Homeodomain Resource: a prototype database for a large protein family SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING; ANTENNAPEDIA HOMEODOMAIN; ENGRAILED HOMEODOMAIN; CRYSTAL-STRUCTURE; COMPLEX; SPECTROSCOPY; SPECIFICITY AB The Homeodomain Resource is an annotated collection of non-redundant protein sequences, three-dimensional structures and genomic information for the homeodomain protein family. Release 2.0 contains 765 full-length,homeodomain-containing sequences, 29 experimentally derived structures and 116 homeobox loci implicated: in human genetic disorders. Entries are fully hyperlinked to facilitate easy retrieval of the original records from source databases. A simple search engine with a graphical user interface is provided to query the component databases and assemble customized data sets. A new feature for this release is the addition of more automated methods for database searching, maintenance and implementation of efficient data management. The Homeodomain Resource is freely available through the WWW at http://genome.nhgri.nih.gov/homeodomain. C1 Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NR 13 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 329 EP 330 DI 10.1093/nar/28.1.329 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300097 PM 10592263 ER PT J AU Smigielski, EM Sirotkin, K Ward, M Sherry, ST AF Smigielski, EM Sirotkin, K Ward, M Sherry, ST TI dbSNP: a database of single nucleotide polymorphisms SO NUCLEIC ACIDS RESEARCH LA English DT Article AB In response to a need for a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, the National Cancer for Biotechnology Information (NCBI) has established the dbSNP database. Submissions to dbSNP will be integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data, The complete contents of dbSNP are available to the public at website:http://www.ncbi.nlm.nih.gov/SNP, Submitted SNPs can also be downloaded via anonymous FTP at ftp://ncbi. nlm.nih.gov/snp/. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Sherry, ST (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 8 TC 182 Z9 192 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 2000 VL 28 IS 1 BP 352 EP 355 DI 10.1093/nar/28.1.352 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 276UT UT WOS:000084896300106 PM 10592272 ER PT J AU Siddiqui, MA Driscoll, JS Abushanab, E Kelley, JA Barchi, JJ Marquez, VE AF Siddiqui, MA Driscoll, JS Abushanab, E Kelley, JA Barchi, JJ Marquez, VE TI The "beta-fluorine effect" in the non-metal hydride radical deoxygenation of fluorine-containing nucleoside xanthates SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article ID HIGHLY DIASTEREOSELECTIVE SYNTHESIS; HIV; RIBONUCLEOSIDES; AGENTS; TIN AB An alternative method to conduct a Barton-McCombie deoxygenation in nucleosides Is described. The utility of the procedure is limited to structures with an electronegative substituent, particularly fluorine, in the beta-position relative to the radical center. The process is radical in nature and triggered by peroxides. The abstraction of hydrogen from the solvent is favorably influenced by the presence of a beta-fluorine. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 25 TC 8 Z9 8 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2000 VL 19 IS 1-2 BP 1 EP 12 DI 10.1080/15257770008032993 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311BC UT WOS:000086863600003 PM 10772699 ER PT J AU Gao, WY Johns, DG Mitsuya, H AF Gao, WY Johns, DG Mitsuya, H TI Potentiation of the anti-HIV activity of zalcitabine and lamivudine by a CTP synthase inhibitor, 3-deazauridine SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; DEOXYRIBONUCLEOSIDE TRIPHOSPHATES; SUBSTRATE CYCLES; ENZYMATIC ASSAY; TYPE-1; HYDROXYUREA; 2',3'-DIDEOXYNUCLEOSIDES; REPLICATION; INVITRO AB Low levels of the CTP synthase inhibitor 3-deazauridine (3-DU) strongly potentiated the anti-HLV-1 activity of the 5'-triphosphates of the cytidine-based analogues [-]2'-deoxy-3'-thiacytidine (3TC; lamivudine) and 2',3'-dideoxycytidine (ddC). The potentiation was associated with a 3-DU-induced decrease in dCTP pool size; no changes were seen in cellular pool sizes of dATP, dGTP or dTTP. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Expt Retrovirol Sect, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Johns, DG (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 18 TC 22 Z9 23 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2000 VL 19 IS 1-2 BP 371 EP 377 DI 10.1080/15257770008033015 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 311BC UT WOS:000086863600025 PM 10772721 ER PT J AU Verheijen, JC Chen, L Bayly, SF Torrence, PF van der Marel, GA van Boom, JH AF Verheijen, JC Chen, L Bayly, SF Torrence, PF van der Marel, GA van Boom, JH TI Synthesis and RNase L binding and activation of a 2-5A-(5 ')-DNA-(3 ')-PNA chimera, a novel potential antisense molecule SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article ID SOLID-PHASE SYNTHESIS; RIBONUCLEASE-L; NUCLEIC-ACIDS; DEGRADATION; DNA; SERUM; OLIGONUCLEOTIDES; PURIFICATION AB Fully automated solid-phase synthesis gave access to a hybrid in which 5'-phosphorylated-2'-5'-linked oligoadenylate (2-5A) is connected to the 5'-terminus of DNA which, in turn, is linked at the 3'-end to PNA [2-5A-(5')-DNA-(3')-PNA chimera]. This novel antisense molecule retains full RNase L activation potency while suffering only a slight reduction in binding affinity. C1 Gorlaeus Labs, Leiden Inst Chem, NL-2300 RA Leiden, Netherlands. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. No Arizona Univ, Dept Chem, Flagstaff, AZ 86011 USA. RP van Boom, JH (reprint author), Gorlaeus Labs, Leiden Inst Chem, POB 9502, NL-2300 RA Leiden, Netherlands. NR 26 TC 5 Z9 5 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PY 2000 VL 19 IS 10-12 SI SI BP 1821 EP 1830 DI 10.1080/15257770008045463 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 389LM UT WOS:000166239400024 PM 11200276 ER PT J AU Davis, JS AF Davis, JS TI Kinetic analysis of dynamics of muscle function SO NUMERICAL COMPUTER METHODS, PART C SE METHODS IN ENZYMOLOGY LA English DT Review ID HUXLEY-SIMMONS PHASE-2; FORCE GENERATION; TENSION TRANSIENTS; TEMPERATURE-JUMP; FIBERS; PHOTOGENERATION; CONTRACTION; TRANSITION; PHOSPHATE; RESPONSES C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Davis, JS (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2000 VL 321 BP 23 EP 37 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ69J UT WOS:000089207400002 PM 10909049 ER PT J AU Dimitriadis, EK Lewis, MS AF Dimitriadis, EK Lewis, MS TI Optimal data analysis using transmitted light intensities in analytical ultracentrifuge SO NUMERICAL COMPUTER METHODS, PART C SE METHODS IN ENZYMOLOGY LA English DT Review C1 NIH, Div Bioengn & Phys Sci, ORS, OD, Bethesda, MD 20892 USA. RP Dimitriadis, EK (reprint author), NIH, Div Bioengn & Phys Sci, ORS, OD, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2000 VL 321 BP 121 EP 136 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ69J UT WOS:000089207400007 PM 10909054 ER PT J AU Lewis, MS Junghans, RP AF Lewis, MS Junghans, RP TI Ultracentrifugal analysis of molecular mass of glycoproteins of unknown or ill-defined carbohydrate composition SO NUMERICAL COMPUTER METHODS, PART C SE METHODS IN ENZYMOLOGY LA English DT Review ID HUMAN INTERLEUKIN-2 RECEPTOR; FC FRAGMENT; TAC ANTIGEN; AMINO-ACID; CELLS; CORE C1 NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Inst Human Genet, Biotherapeut Dev Lab, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. RP Lewis, MS (reprint author), NIH, Div Bioengn & Phys Sci, Bldg 10, Bethesda, MD 20892 USA. NR 22 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2000 VL 321 BP 136 EP 149 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ69J UT WOS:000089207400008 PM 10909055 ER PT J AU van Osdol, WW Myers, TG Weinstein, JN AF van Osdol, WW Myers, TG Weinstein, JN TI Neural network techniques for informatics of cancer drug discovery SO NUMERICAL COMPUTER METHODS, PART C SE METHODS IN ENZYMOLOGY LA English DT Review ID TUMOR-CELL-LINES; DIFFERENTIAL CYTOTOXICITY DATA; MOLECULAR PHARMACOLOGY; SELF-ORGANIZATION; IDENTIFICATION; SCREEN; FEASIBILITY; SENSITIVITY; INHIBITORS; MECHANISM C1 ALZA Corp, Mt View, CA 94043 USA. NCI, Informat Technol Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP van Osdol, WW (reprint author), ALZA Corp, Mt View, CA 94043 USA. NR 45 TC 6 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2000 VL 321 BP 369 EP 395 PG 27 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ69J UT WOS:000089207400020 PM 10909067 ER PT J AU Anderson, G Monsen, RB Prows, CA Tinley, S Jenkins, J AF Anderson, G Monsen, RB Prows, CA Tinley, S Jenkins, J TI Preparing the nursing profession for participation in a genetic paradigm in health care SO NURSING OUTLOOK LA English DT Article ID REVOLUTION AB It is critical that nurses be recognized for their ability to deliver genetic services in collaboration with medical genetics, genetic counselors, physicians, and providers from other disciplines. The purpose of this special communication is to describe progress made by the International Society of Nurses in Genetics toward incorporating genetics into nursing education and practice. C1 Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Bethesda Naval Hosp, NCI, Bethesda, MD USA. NR 27 TC 11 Z9 11 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JAN-FEB PY 2000 VL 48 IS 1 BP 23 EP 27 DI 10.1067/mno.2000.99810 PG 5 WC Nursing SC Nursing GA 293BN UT WOS:000085831800004 PM 10715078 ER PT J AU Ponnamperuma, RM Shimizu, Y Kirchhof, SM De Luca, LM AF Ponnamperuma, RM Shimizu, Y Kirchhof, SM De Luca, LM TI beta-carotene pails to act as a tumor promoter, induces RAR expression, and prevents carcinoma formation in a two-stage model of skin carcinogenesis in male Sencar mice SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID RETINOIC ACID; CANCER CHEMOPREVENTION; MOUSE SKIN; VITAMIN-A; CARDIOVASCULAR-DISEASE; LUNG-CANCER; HIGH-RISK; INHIBITION; PAPILLOMA; RECEPTORS AB Clinical trials have shown a significant increase in incidence of lung cancer among smokers and asbestos workers supplemented with beta-carotene, suggesting a tumor-promoting activity for this agent We set out to test possible tumor-promoting and chemoprerentive activities of dietary and topical beta-carotene in the two-stage 7,12-dimethylbenz[a]anthracene-12-O-tetradecanoylphorbol 13-acetate (TPA) model of mouse skin carcinogenesis. In the first study, the effects of three levels of dietary beta-carotene (6, 60, and 600 mu g/g purified diet containing no other retinoid or carotenoid) were assessed over a period of 42 weeks. Carcinoma yield was reduced by similar to 50% in the 600 mu g/g diet group (mean 0.22 carcinomas/mouse) compared with the 6 mu g/g diet group (mean 0.44 carcinomas/mouse, p = 0003). The 60 mu g/g diet group showed a pattern of inhibition similar to the 600 mu g/g diet group. A protective effect (25% reduction) of beta-carotene (in the 600 mu g/g diet group) on papilloma formation was also found. However, the intermediate 60 mu g/g diet group showed the same incidence as the low 6 mu g/g diet group. This points to a lack of correlation between papilloma and carcinoma incidence, as we also found in previous work on dietary retinoids and carotenoids. The purpose of the second study was to assess whether topical beta-carotene (2 mu g) has hrmor-promoting or chemopreventive activity in the two-stage protocol. In the absence of TPA, beta-carotene had no significant tumor-promoting activity. Instead, papilloma yield induced by TPA was decreased by topical beta-carotene om an average of 20 to similar to 10 papillomas/mouse (p = 2.5 x 10(-7)). The effect of topical p-carotene persisted beyond the treatment period (Week 24) until the termination of the study at Week 42. Western blot analysis of mouse skin extracts showed that topical beta-carotene upregulated retinoic acid receptor-alpha and -gamma expression in the dorsal skin. This finding suggests that beta-carotene may work as a chemopreventive agent by upregulating the expression of retinoid receptors in mouse skin. In conclusion, our data show that beta-carotene prevents skin carcinoma formation, induces retinoic acid receptor expression, and fails to act as a tumor promoter in the two-stage model of skin tumorigenesis. C1 NCI, Differentiat Control Sect, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. ROW Sci, Bethesda, MD 20814 USA. RP De Luca, LM (reprint author), NCI, Differentiat Control Sect, Cellular Carcinogenesis & Tumor Promot Lab, Bldg 37 Rm 3A-17,37 Convent Dr, Bethesda, MD 20892 USA. NR 35 TC 24 Z9 25 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2000 VL 37 IS 1 BP 82 EP 88 DI 10.1207/S15327914NC3701_11 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 344RN UT WOS:000088772800011 PM 10965524 ER PT J AU Cascante, M Centelles, JJ Veech, RL Lee, WNP Boros, LG AF Cascante, M Centelles, JJ Veech, RL Lee, WNP Boros, LG TI Role of thiamin (vitamin B-1) and transketolase in tumor cell proliferation SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Review ID PENTOSE-PHOSPHATE PATHWAY; OXYTHIAMINE; GLUCOSE AB Metabolic control analysis predicts that stimulators of transketolase enzyme synthesis such as thiamin (vitamin B-1) support a high rate of nucleic acid ribose synthesis necessary for tumor cell survival, chemotherapy resistance, and proliferation. Metabolic control analysis also predicts that transketolase inhibitor drugs will have the opposite effect on tumor cells. This may have important implications in the nutrition and future treatment of patients with cancer. C1 Univ Calif Los Angeles, Sch Med, Harbor UCLA Res & Educ Inst, Torrance, CA 90502 USA. Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Dept Biochem & Mol Biol, E-08028 Barcelona, Catalonia, Spain. NIAAA, NIH, Rockville, MD 20852 USA. RP Boros, LG (reprint author), Univ Calif Los Angeles, Sch Med, Harbor UCLA Res & Educ Inst, RB-1,1124 W Carson St, Torrance, CA 90502 USA. EM boros@gcrc.humc.edu RI Centelles, Josep Joan/K-2972-2014 OI Centelles, Josep Joan/0000-0002-6289-9678 NR 32 TC 39 Z9 44 U1 1 U2 8 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2000 VL 36 IS 2 BP 150 EP 154 DI 10.1207/S15327914NC3602_2 PG 5 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 327PX UT WOS:000087802900002 PM 10890024 ER PT J AU Tseng, M Ingram, DD Darden, R Ziegler, RG Longnecker, MP AF Tseng, M Ingram, DD Darden, R Ziegler, RG Longnecker, MP TI Eating frequency and risk of colorectal cancer SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID COLON-CANCER; MEAL FREQUENCY; FOLLOW-UP; DIET AB Case-control studies have found elevated risk of colorectal cancer with higher eating frequency. The present analyses, the first to examine this association using prospectively collected information, utilized nationally representative data from the Epidemiologic Follow-Up Study of the First National Health and Nutrition Examination Survey (NHEFS). The study population included 9,978 subjects followed from 1982-84 to 1992. Colorectal cancer cases (n = 141) were identified by self-report, hospital records, and death certificates. Interviews conducted in 1982-84 provided information on meal and snack frequencies and covariates of interest. Relative risk (RR) of colorectal cancer and 95% confidence intervals (CI) were estimated using Cox proportional hazards models adjusted for age, gender, and race and energy, alcohol, total fat, and fiber intake. Compared with those eating <3 times/day, those eating 3-4 times/day had an RR of 0.66 (95% CI = 0.42-1.03) and those eating >4 times/day had an RR of 0.74 (95% CI = 0.41-1.32). The association was due to decreased risk with more meals rather than more snacks per day. Given limitations of previous studies as well as the possibility of a protective effect of higher eating frequency through improved glycemic control, the present findings suggest that the influence of eating frequency on colorectal cancer risk is more complex than has been previously supposed and merits additional study. C1 Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. WESTAT Corp, Durham, NC 27703 USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Tseng, M (reprint author), Fox Chase Canc Ctr, Div Populat Sci, 7701 Burholme Ave, Philadelphia, PA 19111 USA. RI Tseng, Marilyn/B-9334-2016; OI Tseng, Marilyn/0000-0002-9969-9055; Longnecker, Matthew/0000-0001-6073-5322 NR 23 TC 6 Z9 6 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2000 VL 36 IS 2 BP 170 EP 176 DI 10.1207/S15327914NC3602_5 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 327PX UT WOS:000087802900005 PM 10890027 ER PT J AU Habash, T Eskay, RL Kuenzel, WJ Castonguay, TW AF Habash, T Eskay, RL Kuenzel, WJ Castonguay, TW TI Interactions of glucocorticoids, NPY and hypothalamic serotonin SO NUTRITIONAL NEUROSCIENCE LA English DT Article DE adrenalectomy; corticosterone; food intake; hypothalamus; insulin ID OBESE ZUCKER RATS; MESSENGER-RIBONUCLEIC-ACID; NEUROPEPTIDE-Y; PARAVENTRICULAR NUCLEUS; FEEDING-BEHAVIOR; FOOD-DEPRIVATION; INTRACEREBROVENTRICULAR INFUSION; ENERGY-METABOLISM; BODY-WEIGHT; INSULIN AB Neuropeptide Y (NPY), insulin, corticosterone (CORT) and 5-hydroxytryptamine (5-HT), or serotonin, are all involved in energy homeostasis. To show how they might interact, the effects of NPY on plasma insulin and on 5-HT metabolism in the paraventricular hypothalamic nucleus (PVN), the ventromedial hypothalamic nucleus (VMN), the arcuate nucleus (ARC), and the locus coeruleus (LC) were measured in separate groups of intact, adrenalectomized (ADX), or ADX and CORT replaced Sprague-Dawley rats. Fifteen minutes after ICV injection of NPY, no effect on 5-HT metabolism in the intact animal was observed. 5-HT and its metabolite, 5-HIAA, increased in the PVN as a result of ADX, an eff ect that was reversed with CORT replacement. NPY also reversed these effects. Similar effects of ADX, CORT replacement and NPY were noted with 5-HIAA in the ARC. This suggests a role for 5-HT in the attenuation of weight gain in ADX animals. NPY also caused an increase in plasma insulin in the CORT replaced animal, but not the intact animal. This was most likely due to an inability of CORT replaced animals to adjust their CORT levels in response to NPY. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. NIAAA, NIH, Bethesda, MD 20892 USA. RP Castonguay, TW (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. OI Castonguay, Thomas/0000-0003-1176-5095 NR 40 TC 1 Z9 1 U1 0 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1028-415X J9 NUTR NEUROSCI JI Nutr. Neurosci. PY 2000 VL 3 IS 3 BP 183 EP 192 PG 10 WC Neurosciences; Nutrition & Dietetics SC Neurosciences & Neurology; Nutrition & Dietetics GA 380FH UT WOS:000165688800004 PM 27414052 ER PT J AU Shen, DF Buggage, RR Eng, HC Chan, CC AF Shen, DF Buggage, RR Eng, HC Chan, CC TI Cytokine gene expression in different strains of mice with endotoxin-induced uveitis (EIU) SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article; Proceedings Paper CT Annaul Meeting of the Society-for-Ocular-Immunoinfectiology (SOIE 2000) CY MAR 17-19, 2000 CL PARIS, FRANCE DE cytokine; endotoxin-induced uveitis ( EIU); interleukin-6 (IL-6); RT-PCR; mouse ID TUMOR-NECROSIS-FACTOR; MACROPHAGE; RAT; INDUCTION AB Purpose: The kinetics of various cytokines in the eye plays a critical role in endotoxin-induced uveitis (EIU). This study examined the cytokine kinetics and susceptibility of EIU in four mice strains. Methods: Four strains of TLR-4 or Toll-like receptor-4 (Lps, lipopolysaccharide-susceptible) gene-positive mice (C3H/HeN of H-2(k), C-57/B6 of H-2(b), Balb/C of H-2(d), and 129/J of H-2(b)) were injected subcutaneously with either lipopolysaccharide (LPS) in phosphate-buffered saline ( PBS) or PBS alone in two repeated experiments. Mice were sacrificed 1, 3, 6, 24 (1 d), 72 (3 d), 120 (5 d), or 168 (7 d) hours after LPS injection. Ocular histology and reverse transcriptase-polymerase chain reaction (RT-PCR) to detect ocular interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA were performed. Serum IL-1, IL-1, IL-6, and TNF-alpha levels were measured using enzyme-linked immunosorbent assay ( ELISA). Results: No ocular inflammation was present in any mice within six hours after LPS injection. Only the C3H/HeN mice developed a biphasic ocular inflammatory response ( 1 d and 5 d), during which all proinflammatory cytokine messages were expressed. In the other three strains with minimal (129/J and Balb/C) to mild (C-57/B6) EIU that peaked at 1 d, IL-6 mRNA was barely detectable in C-57/B6 and Balb/C; GM-CSF mRNA was also present in C-57/B6. Serum IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha were high in all EIU mice within six hours after LPS injection. Control mice did not develop uveitis or measurable cytokine messages. Conclusion: In the most susceptible strain, C3H/HeN, EIU was biphasic and correlated to multiple proinflammatory cytokines released in the eye. The less susceptible mice strains exhibited a monophasic response to LPS that may result from no cytokine cascade. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Mol Signaling & Oncogenesis, NIH, Bethesda, MD 20892 USA. Duke Univ, Durham, NC USA. RP Chan, CC (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. NR 14 TC 16 Z9 17 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2000 VL 8 IS 4 BP 221 EP 225 DI 10.1076/ocii.8.4.221.6461 PG 5 WC Ophthalmology SC Ophthalmology GA 395QR UT WOS:000166592700002 PM 11262651 ER PT J AU Cassoux, N Merle-Beral, H Leblond, V Bodaghi, B Milea, D Gerber, S Fardeau, C Reux, I Xuan, KH Chan, CC LeHoang, P AF Cassoux, N Merle-Beral, H Leblond, V Bodaghi, B Milea, D Gerber, S Fardeau, C Reux, I Xuan, KH Chan, CC LeHoang, P TI Ocular and central nervous system lymphoma: clinical features and diagnosis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article; Proceedings Paper CT Annaul Meeting of the Society-for-Ocular-Immunoinfectiology (SOIE 2000) CY MAR 17-19, 2000 CL PARIS, FRANCE DE ocular lymphoma; cerebral lymphoma; diagnostic vitrectomy; PCR; chemotherapy ID PRIMARY INTRAOCULAR LYMPHOMA; RETICULUM-CELL SARCOMA; POLYMERASE-CHAIN-REACTION; COMBINED-MODALITY THERAPY; PRIMARY CNS LYMPHOMA; INCREASING INCIDENCE; CHEMOTHERAPY; MICRODISSECTION; INTERLEUKIN-10; MANAGEMENT AB Purpose: To evaluate the clinical, angiographic, and cytopathologic features of ocular and central nervous system (CNS) lymphoma. Patients and methods: Retrospective study of 44 patients over a 10-year period. Results: A total of 36 women and six men, mean age 54 years (range: 36-90 years), were included. The mean time interval between onset of ocular symptoms and diagnosis was 40 months (range: 1-144 months). Ocular involvement was bilateral in 84% of the cases. Laser flare photometry readings averaged 9.6 photons/ms (2.9-78.3 photons/ms). Vitritis was constant. Funduscopy revealed RPE abnormalities in 60.49% of the cases and punctuate retinal infiltrates in 33.5%. The most common findings with fluorescein angiography were window defects and hypofluorescent round lesions. Patients had CNS involvement in 66% of the cases. Cytologic examination of the vitreous samples showed high-grade B lymphoma in 86% of the cases. Interleukin-10 dosage, when performed, showed elevated levels averaging 2352 pg/ml in all vitreous samples. Molecular biology based on PCR confirmed the diagnosis in 12 patients. Treatment included systemic chemotherapy alone or associated with radiotherapy in various regimens. Fourteen patients died during follow-up. Only 12 patients were in complete remission. Conclusion: The prognosis of the disease remains poor. However, the new diagnostic tools and therapeutic strategies may improve the diagnostic delay and the survival outcome. C1 Hop La Pitie Salpetriere, Dept Ophthalmol, F-75651 Paris 13, France. Hop La Pitie Salpetriere, Dept Hematol, F-75651 Paris, France. Hop La Pitie Salpetriere, Dept Neuroradiol, F-75651 Paris 13, France. Hop La Pitie Salpetriere, Dept Neurol, F-75651 Paris 13, France. NIH, Dept Immunol, Bethesda, MD 20892 USA. RP LeHoang, P (reprint author), Hop La Pitie Salpetriere, Dept Ophthalmol, 47-83 Bd Hop, F-75651 Paris 13, France. RI Cassoux, Nathalie/D-6844-2015 OI Cassoux, Nathalie/0000-0002-5535-9649 NR 30 TC 83 Z9 85 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2000 VL 8 IS 4 BP 243 EP 250 DI 10.1076/ocii.8.4.243.6463 PG 8 WC Ophthalmology SC Ophthalmology GA 395QR UT WOS:000166592700005 PM 11262654 ER PT J AU Pearson, JL AF Pearson, JL TI Preventing late life suicide: National institutes of health initiatives SO OMEGA-JOURNAL OF DEATH AND DYING LA English DT Article ID PRIMARY-CARE; PSYCHOLOGICAL AUTOPSY; DEPRESSION; MANAGEMENT; BEHAVIOR; PEOPLE AB From a public health perspective, late life suicide is seen primarily as a consequence of untreated mental disorder, particularly depression. However, due to the stigma and agism surrounding mental disorders in late life, there has been limited public awareness that the elderly have the highest rates of suicide, and that they often have treatable depression prior to their suicide. Late life suicide is slowly gaining attention in both the scientific and public arenas. This article reviews in chronological order a number of efforts that have led to heightened awareness and initial public health policy development of late life suicide prevention strategies. The next steps for NIH-sponsored research in late life suicide are described. C1 NIMH, Bethesda, MD 20892 USA. RP Pearson, JL (reprint author), NIMH, 6001 Execut Blvd,Rm 7160,MSC 9635, Bethesda, MD 20892 USA. NR 43 TC 1 Z9 1 U1 6 U2 8 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0030-2228 J9 OMEGA-J DEATH DYING JI Omega-J. Death Dying PY 2000 VL 42 IS 1 BP 9 EP 20 DI 10.2190/FMRG-87W0-YXDK-6EFY PG 12 WC Psychology, Multidisciplinary; Social Sciences, Biomedical SC Psychology; Biomedical Social Sciences GA 428MZ UT WOS:000168466600002 ER PT J AU Shillitoe, EJ May, M Patel, V Lethanakul, C Ensley, JF Strausberg, RL Gutkind, JS AF Shillitoe, EJ May, M Patel, V Lethanakul, C Ensley, JF Strausberg, RL Gutkind, JS TI Genome-wide analysis of oral cancer - early results from the Cancer Genome Anatomy Project SO ORAL ONCOLOGY LA English DT Article DE oral cancer; gene expression; CGAP ID SQUAMOUS-CELL CARCINOMAS; EXPRESSION; HEAD; NECK; P53; SEQUENCE; SURVIVAL; BCL-2; GENES AB The Cancer Genome Anatomy Project (CGAP) is a large cooperative effort sponsored by the US National Institutes of Health designed to End, catalog and annotate genes that are expressed during cancer development. In the past 2 years, the CGAP has sequenced over 700,000 clones from approximately 140 cDNA libraries, resulting in the identification of over 30,000 new human genes. As a first seep in applying this project to oral cancer we entered four cell lines-two from oral cancer, one from primary oral keratinocytes, and one from oral keratinocytes which had been immortalized by human papillomavirus. Libraries of cDNA were made and sequenced and the data were deposited in GenBank. The expressed genes were then identified where possible. The call lines, and the total number of expressed genes that were cloned from each were: HN3 (oral cancer), 263 genes; HN4 (oral cancer), 550 genes; HN5 (primary keratinocytes), 237 genes; HN6 (immortalized keratinocytes), 408 genes. The total number of different genes that were found was 1160. A total of 38 new genes, of unknown function, were discovered. The data presented here represent a beginning of the application of the CGAP technology to oral cancer. Even though the data are still quite incomplete, they already represent a large quantity of new information and clones of potential utility to the oral cancer community, and provide a glimpse of the data sets to be forthcoming from the Project. It must therefore be expected that there will soon be a large expansion in the volume of data regarding the genetics of oral cancer. Those who study this disease must be prepared to develop new methods of analysis and storage for handling the oncoming volumes of information. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 SUNY Coll Med, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Dept Hematol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI 48201 USA. NCI, Canc Genom Off, Bethesda, MD 20892 USA. RP SUNY Coll Med, Dept Microbiol & Immunol, 750 E Adams St, Syracuse, NY 13210 USA. EM shillite@hscsyr.edu RI Gutkind, J. Silvio/A-1053-2009 NR 26 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD JAN PY 2000 VL 36 IS 1 BP 8 EP 16 DI 10.1016/S1368-8375(99)00071-8 PG 9 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 275AC UT WOS:000084796400003 PM 10889913 ER PT J AU LaCour, TG Guo, CX Boyd, MR Fuchs, PL AF LaCour, TG Guo, CX Boyd, MR Fuchs, PL TI Cephalostatin support studies. Part 19. Outer-ring stereochemical modulation of cytotoxicity in cephalostatins SO ORGANIC LETTERS LA English DT Article ID TUNICATE RITTERELLA-TOKIOKA; RITTERAZINE-B; PYRAZINES AB [GRAPHICS] 20- and 25'-epimers of cephalostatin 7, prepared by directed unsymmetrical pyrazine synthesis, address outer-ring topographical and stability questions and intimate an oxacarbenium ion rationale for the role in bioactivity of the spiroketal (E/F, E'/F') rings of this class of antitumor agents. C1 Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. NCI, Frederick Canc Res Ctr, Frederick, MD 21702 USA. RP LaCour, TG (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. FU NCI NIH HHS [CA 60548] NR 23 TC 28 Z9 28 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JAN PY 2000 VL 2 IS 1 BP 33 EP 36 DI 10.1021/ol991153y PG 4 WC Chemistry, Organic SC Chemistry GA 288GN UT WOS:000085554500010 PM 10814239 ER PT J AU Hirsch, R Guralnik, JM Ling, SM Fried, LP Hochberg, MC AF Hirsch, R Guralnik, JM Ling, SM Fried, LP Hochberg, MC TI The patterns and prevalence of hand osteoarthritis in a population of disabled older women: The Women's Health and Aging Study SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article; Proceedings Paper CT 2nd International Workshop on Hand Osteoarthritis CY MAY 21-22, 1999 CL BOSTON, MASSACHUSETTS SP Labs Pharmasclence DE prevalence; hand osteoarthritis; disabled older women ID OSTEO-ARTHRITIS; RADIOGRAPHIC OSTEOARTHRITIS; JOINT DISEASES; HAVEN SURVEY; DISABILITY; CRITERIA; PEOPLE AB Objective. To describe the prevalence of hand osteoarthritis (OA) by joint site, joint count and severity in a representative population of older disabled women. Methods: 1002 moderately to severely disabled women aged greater than or equal to 65 years were selected from a representative population of community-dwelling women. Hand OA was established using a reproducible algorithm based on self-reported pain, standardized physical examinations, hand photographs, and physician questionnaire responses. OA was categorized as either symptomatic disease, intermittently symptomatic/asymptomatic disease, possible disease, or no disease. Results: Symptomatic OA, requiring the presence of hand pain on most days for at least 1 month, occurred in approximately 23% of disabled older women in each age group, and most reported pain in the moderate to severe range. The prevalence of intermittently symptomatic/asymptomatic OA was higher with increasing age. Finally, the most commonly affected hand OA sites were the distal interphalangeal (DIP) and the first carpometacarpal (CMC1) joint groups. Conclusion: These findings demonstrate the very high prevalence of clinical hand OA in disabled older women and show that a large proportion of hand OA results in substantial symptoms. (C) 2000 OsteoArthritis Research Society International. C1 NIA, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Geriatr & Gerontol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Rheumatol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. RP Hirsch, R (reprint author), NIA, NIH, Gateway Bldg,Room 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. FU NIA NIH HHS [N01-AG-1-2112] NR 25 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PY 2000 VL 8 SU A BP S16 EP S21 PG 6 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 382TC UT WOS:000165837700006 PM 11156487 ER PT J AU Robbins, JA Hirsch, CH Whitmer, R Cauley, J Harris, TB Davis, UC AF Robbins, JA Hirsch, CH Whitmer, R Cauley, J Harris, TB Davis, UC TI Association of BMI and depression in an elderly population SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIA, Bethesda, MD 20892 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2000 VL 11 SU 2 MA 210 BP S112 EP S113 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337GB UT WOS:000088348100231 ER PT J AU Zmuda, JM Cauley, JA Kuller, LH Newman, AB Robbins, J Harris, T Ferrell, RE AF Zmuda, JM Cauley, JA Kuller, LH Newman, AB Robbins, J Harris, T Ferrell, RE TI Androgen receptor CAG repeat polymorphism: A novel molecular marker of osteoporotic risk in men SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif Davis, Davis, CA 95616 USA. NIA, Bethesda, MD 20892 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 2000 VL 11 SU 2 MA 355 BP S151 EP S151 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337GB UT WOS:000088348100374 ER PT B AU Sterneck, E Johnson, PF AF Sterneck, E Johnson, PF BE Adashi, EY TI Expression and function of CCAAT/enhancer binding proteins (C/EBPs) in the ovary SO OVULATION: EVOLVING SCIENTIFIC AND CLINICAL CONCEPTS SE SERONO SYMPOSIA, USA LA English DT Proceedings Paper CT International Symposium on Ovulation - Evolving Scientific and Clinical Concepts CY SEP 24-27, 1998 CL SALT LAKE CITY, UT SP Serono Symposia USA ID PROSTAGLANDIN ENDOPEROXIDE SYNTHASE-2; LEUCINE-ZIPPER; DNA-BINDING; TRANSCRIPTION FACTOR; GRANULOSA-CELLS; GENE-TRANSCRIPTION; BASIC REGION; RAT OVARY; MYELOMONOCYTIC CELLS; NEGATIVE INHIBITOR C1 NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Mol Mech Dev Grp, Frederick, MD 21702 USA. RP Sterneck, E (reprint author), NCI, Frederick Canc Res & Dev Ctr, Regulat Cell Growth Lab, Mol Mech Dev Grp, Frederick, MD 21702 USA. NR 62 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-95124-5 J9 SERONO SYMP PY 2000 BP 277 EP 291 PG 15 WC Endocrinology & Metabolism; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA BR70S UT WOS:000167234000023 ER PT S AU Murray, EA Bussey, TJ Hampton, RR Saksida, LM AF Murray, EA Bussey, TJ Hampton, RR Saksida, LM BE Scharfman, HE Witter, MP Schwarcz, R TI The parahippocampal region and object identification SO PARAHIPPOCAMPAL REGION: IMPLICATIONS FOR NEUROLOGICAL AND PSYCHIATRIC DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Hippocampal Region - Basic Science and Clinical Implications CY SEP 23-26, 1999 CL BALTIMORE, MARYLAND SP New York Acad Sci, NIH ID PERIRHINAL CORTEX ABLATION; RHINAL CORTEX; RHESUS-MONKEYS; MEMORY IMPAIRMENT; INFEROTEMPORAL CORTEX; VISUAL RECOGNITION; RETROGRADE-AMNESIA; LESIONS; RATS; FORNIX AB The hippocampus has long been thought to be critical for memory, including memory for objects. However, recent neuropsychological studies in nonhuman primates have indicated that other regions within the medial temporal lobe, specifically, structures in the parahippocampal region, are primarily responsible for object recognition and object identification. This article reviews the behavioral effects of removal of structures within the parahippocampal region in monkeys, and cites relevant work in rodents as well. It is argued that the perirhinal cortex, in particular, contributes to object identification in at least two ways: (i) by serving as the final stage in the ventral visual cortical pathway that represents stimulus features, and (ii) by operating as part of a network for associating together sensory inputs within and across sensory modalities. C1 NIMH, Lab Neuropsychol, Bethesda, MD 20892 USA. RP Murray, EA (reprint author), NIMH, Lab Neuropsychol, Bldg 49,Room 1B80,49 Convent Dr, Bethesda, MD 20892 USA. RI Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016; OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642 NR 42 TC 71 Z9 71 U1 1 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-263-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2000 VL 911 BP 166 EP 174 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BQ52E UT WOS:000088609700011 PM 10911873 ER PT S AU Brown, KE Young, NS AF Brown, KE Young, NS BE Faisst, S Rommelaere, J TI Epidemiology and pathology of erythroviruses SO PARVOVIRUSES: FROM MOLECULAR BIOLOGY TO PATHOLOGY AND THERAPEUTIC USES SE CONTRIBUTIONS TO MICROBIOLOGY LA English DT Proceedings Paper CT 7th International Parvovirus Workshop CY SEP, 1997 CL HEIDELBERG, GERMANY ID HUMAN PARVOVIRUS B19; HEMATOPOIETIC PROGENITOR CELLS; ERYTHROID LINEAGE CELLS; HUMAN-BONE MARROW; ERYTHEMA-INFECTIOSUM; SIMIAN PARVOVIRUS; P-ANTIGEN; NONSTRUCTURAL PROTEIN; CYNOMOLGUS MONKEYS; PERIPHERAL-BLOOD C1 NIH, Bethesda, MD 20892 USA. RP Brown, KE (reprint author), NIH, Bldg 10,Room 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 75 TC 1 Z9 1 U1 1 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1420-9519 BN 3-8055-6946-7 J9 CONTRIB MICROBIOL PY 2000 VL 4 BP 107 EP 122 PG 16 WC Microbiology; Virology SC Microbiology; Virology GA BS87Y UT WOS:000171311900007 PM 10941573 ER PT B AU Maronpot, RR Flagler, ND Ton, TVT Foley, JF Goldsworthy, TL AF Maronpot, RR Flagler, ND Ton, TVT Foley, JF Goldsworthy, TL BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Measurement of cell replication and apoptosis in mice SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID ARCHIVAL RODENT TISSUES; NUCLEAR ANTIGEN; RAT-LIVER; S-PHASE; HEPATOCELLULAR PROLIFERATION; TRITIATED-THYMIDINE; CYCLE PROGRESSION; GROWTH-FACTOR; DEATH; BROMODEOXYURIDINE C1 NIH, Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Maronpot, RR (reprint author), NIH, Natl Inst Environm Hlth Sci, Lab Expt Pathol, POB 12233, Res Triangle Pk, NC 27709 USA. EM Maronpot@niehs.nih.gov; Maronpot@niehs.nih.gov NR 88 TC 1 Z9 1 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 45 EP 60 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800005 ER PT B AU Ward, JM Devor-Henneman, DE AF Ward, JM Devor-Henneman, DE BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Gestational mortality in genetically engineered mice: Evaluating the extraembryonal embryonic placenta and membranes SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID LEUKEMIA INHIBITORY FACTOR; RECEPTOR TYROSINE KINASE; BLOOD-VESSEL DEVELOPMENT; TARGETED DISRUPTION; DEFICIENT MICE; TISSUE FACTOR; CELLULAR PROLIFERATION; VASCULAR DEVELOPMENT; MESODERMAL DEFECTS; EGF RECEPTOR C1 NIH, NCI, NCIFCRDC, Off Lab Anim Resources,Vet & Tumor Pathol Sect, Frederick, MD 21702 USA. RP Ward, JM (reprint author), NIH, NCI, NCIFCRDC, Off Lab Anim Resources,Vet & Tumor Pathol Sect, Frederick, MD 21702 USA. NR 78 TC 8 Z9 8 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 103 EP 122 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800008 ER PT B AU Jacobowitz, DM Abbott, LC Kallarakal, AT Tohda, C Lau, FC Gillespie, JW AF Jacobowitz, DM Abbott, LC Kallarakal, AT Tohda, C Lau, FC Gillespie, JW BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Normal brain development and gene discovery in the embryo SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH C1 NIH, NIMH, Clin Sci Lab, Sect Histopharmacol, Bethesda, MD 20892 USA. RP Jacobowitz, DM (reprint author), NIH, NIMH, Clin Sci Lab, Sect Histopharmacol, Bldg 10,Room 3D-48, Bethesda, MD 20892 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 123 EP 134 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800009 ER PT B AU Mahler, JF AF Mahler, JF BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Genetic background effects on the interpretation of phenotypes in induced mutant mice SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID INTESTINAL NEOPLASIA; TRANSGENIC MICE; MOUSE MODELS; DISEASE; STRAIN; RECEPTOR; CANCER; SUSCEPTIBILITY; SENSITIVITY; DISRUPTION C1 NIH, Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Mahler, JF (reprint author), NIH, Natl Inst Environm Hlth Sci, Lab Expt Pathol, POB 12233, Res Triangle Pk, NC 27709 USA. NR 44 TC 3 Z9 3 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 137 EP 144 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800010 ER PT B AU Devor-Henneman, DE AF Devor-Henneman, DE BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Clinical evaluation of genetically engineered mice SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH C1 NCI, Frederick Canc Res & Dev Ctr, Vet & Tumor Pathol Sect, Frederick, MD 21702 USA. RP Devor-Henneman, DE (reprint author), NCI, Frederick Canc Res & Dev Ctr, Vet & Tumor Pathol Sect, Frederick, MD 21702 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 145 EP 154 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800011 ER PT B AU Ward, JM AF Ward, JM BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Pathology phenotyping of genetically engineered mice SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID RECEPTOR-DEFICIENT MICE; MOUSE GENOME; TARGETED DISRUPTION; TRANSGENIC MICE; KNOCKOUT MICE; DISEASE; COMPENDIUM; MODELS; MUTANT; GENE C1 NCI, Frederick Canc Res & Dev Ctr,NIH, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Frederick, MD 21702 USA. RP Ward, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr,NIH, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Frederick, MD 21702 USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 155 EP 160 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800012 ER PT B AU Ward, JM Anver, MR Mahler, JF Devor-Henneman, DE AF Ward, JM Anver, MR Mahler, JF Devor-Henneman, DE BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Pathology of mice commonly used in genetic engineering (C57BL/6; 129; B6,129; and FVB/N) SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID WILD-TYPE MICE; SPONTANEOUS LESIONS; P53-DEFICIENT MICE; INBRED STRAIN; RESTRICTION; MOUSE; MUTANT; CELL C1 NCI, Frederick Canc Res & Dev Ctr,NIH, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Frederick, MD 21702 USA. RP Ward, JM (reprint author), NCI, Frederick Canc Res & Dev Ctr,NIH, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Frederick, MD 21702 USA. NR 48 TC 36 Z9 36 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 161 EP 179 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800013 ER PT B AU Crawley, JN AF Crawley, JN BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Strategies for behavioral phenotyping of transgenic and knockout mice SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID MORPHINE-INDUCED ANALGESIA; TARGETED DISRUPTION; GENE; LACKING; ABNORMALITIES; PARTURITION; DISEASES; OXYTOCIN; STRAINS; MODELS C1 NIMH, Behav Neuropharmacol Sect, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Crawley, JN (reprint author), NIMH, Behav Neuropharmacol Sect, Expt Therapeut Branch, NIH, Bldg10,Room 4D11, Bethesda, MD 20892 USA. NR 32 TC 0 Z9 0 U1 1 U2 2 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 233 EP 238 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800016 ER PT B AU Mahler, M Rozell, B Mahler, JF Merlino, G Devor-Henneman, D Ward, JM Sundberg, JP AF Mahler, M Rozell, B Mahler, JF Merlino, G Devor-Henneman, D Ward, JM Sundberg, JP BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Pathology of the gastrointestinal tract of genetically engineered and spontaneous mutant mice SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID GROWTH-FACTOR-ALPHA; INFLAMMATORY BOWEL-DISEASE; MULTIPLE INTESTINAL NEOPLASIA; 2 INBRED STRAINS; CD4(+) T-CELLS; FAMILIAL ADENOMATOUS POLYPOSIS; INTERLEUKIN-2 DEFICIENT MICE; TRANSGENIC MOUSE MODELS; TOOTH ERUPTION; APC GENE C1 NIEHS, Lab Exptl Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Mahler, M (reprint author), NIEHS, Lab Exptl Pathol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 181 TC 6 Z9 7 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 269 EP 297 PG 29 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800019 ER PT B AU Mahler, JF AF Mahler, JF BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Pathology of the reproductive system in genetically engineered and spontaneous mutant mice SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID FOLLICLE-STIMULATING-HORMONE; ESTROGEN-RECEPTOR GENE; TUMOR-SUPPRESSOR GENE; GERM-CELL APOPTOSIS; LARGE-T-ANTIGEN; TRANSGENIC MICE; TARGETED DISRUPTION; DEFICIENT MICE; OVARIAN-TUMORS; GROWTH-FACTOR C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Mahler, JF (reprint author), NIEHS, Lab Expt Pathol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 73 TC 0 Z9 0 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 337 EP 346 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800022 ER PT B AU Eckhaus, MA Kopp, JB AF Eckhaus, MA Kopp, JB BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Renal diseases in genetically engineered mice SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID POLYCYSTIC KIDNEY-DISEASE; ANGIOTENSIN-CONVERTING ENZYME; SALT-SENSITIVE HYPERTENSION; ATRIAL-NATRIURETIC-PEPTIDE; BRADYKININ B-2 RECEPTOR; BETA TRANSGENIC MICE; GROWTH FACTOR-I; BLOOD-PRESSURE; PROGRESSIVE GLOMERULOSCLEROSIS; GENE-EXPRESSION C1 NIH, Off Res Serv, Vet Resources Program, Bethesda, MD 20892 USA. RP Eckhaus, MA (reprint author), NIH, Off Res Serv, Vet Resources Program, Bethesda, MD 20892 USA. NR 101 TC 2 Z9 2 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 347 EP 364 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800023 ER PT B AU Taddesse-Heath, L Morse, HC AF Taddesse-Heath, L Morse, HC BE Ward, JM Mahler, JF Maronpot, RR Sundberg, JP TI Lymphomas in genetically engineered mice SO PATHOLOGY OF GENETICALLY ENGINEERED MICE LA English DT Proceedings Paper CT Symposium on the Pathology of Genetically-Engineered Mice CY 1999 CL NIH, BETHESDA, MD SP NCI HO NIH ID TUMOR-SUPPRESSOR GENE; T-CELL LYMPHOMAS; TRANSGENIC MICE; B-CELL; COMPOSITE LYMPHOMA; TARGETED MUTATION; RAPID DEVELOPMENT; MOUSE MODELS; C-MYC; N-MYC C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Taddesse-Heath, L (reprint author), NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NR 59 TC 10 Z9 10 U1 0 U2 0 PU IOWA STATE UNIV PRESS PI AMES PA 2121 STATE AVE, AMES, IA 50014-8300 USA BN 0-8138-2521-0 PY 2000 BP 365 EP 381 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pathology SC Biochemistry & Molecular Biology; Pathology GA BR80H UT WOS:000167601800024 ER PT J AU Hori, M Inagawa, S Shimazaki, J Itabashi, M Hori, M AF Hori, M Inagawa, S Shimazaki, J Itabashi, M Hori, M TI Overexpression of mitogen-activated protein kinase superfamily proteins unrelated to Ras and AF-1 of estrogen receptor alpha mutation in advanced stage human breast cancer SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE mitogen-activated protein kinase; Ras oncogene; estrogen receptor alpha; activation function-1; human breast cancer ID MAP KINASE; GENE; CELLS; PHOSPHATASE; EXPRESSION; CARCINOMA; TAMOXIFEN; PHOSPHORYLATION; CARCINOGENESIS; LOCALIZATION AB Transactivation of the activation function-1 (AF-1) region of the estrogen receptor alpha (ER-alpha) gene is regulated by pathway "cross-talk" from Ras mitogen-activated protein kinase (MAPK). An analysis of this system is important for solving the problem of resistance to anti-estrogen agents used in the treatment of human breast cancer. We investigated the ER-alpha and Ras gene mutations and the MAPK-related protein status in 103 cases of breast cat-cinema. None of the cases showed mutations in the AF-1 region of the ER-alpha gene. Despite the extremely low frequency of K- and H-Ras mutations in codon 12(2/103 and 0/103), Ras p21 overexpression was identified in 29.1% (30/103), suggesting that the Ras activation in almost all cases we studied was not caused by point mutations but by enhanced expression. Our immunohistochemical analysis showed that the cases with overexpression of Ras and MAPK proteins (Ras p21, ERK-1, JNK-1, and p38) had a progressive tendency towards invasive growth, advanced-stage cancer, and decreased levels of ER-alpha protein. These results suggest that enhanced MAPK activity could be one of the characteristics of advanced breast cancer and that it could be involved in the transformation into estrogen-independent growth. C1 Ibaraki Prefectural Cent Hosp & Canc Ctr, Dept Pathol, Ibaraki, Osaka 3091703, Japan. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Hori, M (reprint author), Ibaraki Prefectural Cent Hosp & Canc Ctr, Dept Pathol, 6528 Koibuchi, Ibaraki, Osaka 3091703, Japan. EM ms-hori@chubyoin.pref.ibaraki.jp NR 39 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2000 VL 196 IS 12 BP 817 EP 826 PG 10 WC Pathology SC Pathology GA 389AH UT WOS:000166215000003 PM 11156322 ER PT J AU Nanni, L Schelper, RL Muenke, M AF Nanni, L Schelper, RL Muenke, M TI Molecular genetics of holoprosencephaly SO PEDIATRIC PATHOLOGY & MOLECULAR MEDICINE LA English DT Review DE holoprosencephaly; forebrain development; Sonic Hedgehog; ZIC2; SIX3; Nodal; TGIF; review ID LEMLI-OPITZ-SYNDROME; SONIC-HEDGEHOG GENE; MURINE HOMEOBOX GENE; CRITICAL REGION; RETINOIC ACID; FOREBRAIN DEVELOPMENT; REDUCTASE GENE; NEURAL-TUBE; MUTATIONS; DROSOPHILA AB Holoprosencephaly (HPE) is a common developmental defect of the human forebrain and midface. Pathological studies have identified different categories of severity of the brain and craniofacial malformations observed in HPE, although the variable clinical spectrum of HPE extends in unbroken sequence from alobar HPE and cyclopia to clinically unaffected carriers in familial HPE. The etiology of HPE is extremely heterogeneous including both environmental and genetic causes. Here we focus on molecular aspects of HPE in light of the recent identification of some of the genes causing human HPE and other candidate genes involved in forebrain development, through different approaches, such as positional cloning and functional cloning, based on animal models. These approaches will aid in the identification of additional genes involved in HPE and in a better understanding of the molecular genetics of brain development. C1 Univ Penn, Sch Med, Dept Pediat, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurol, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. SUNY Hlth Sci Ctr, Dept Pathol, Syracuse, NY 13120 USA. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,10C101, Bethesda, MD 20892 USA. NR 83 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1522-7952 J9 PEDIATR PATHOL MOL M JI Pediatr. Pathol. Mol. Med. PD JAN-FEB PY 2000 VL 19 IS 1 BP 1 EP 19 PG 19 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 330JB UT WOS:000087958100001 ER PT J AU Wu, SM Leschek, EW Rennert, OM Chan, WY AF Wu, SM Leschek, EW Rennert, OM Chan, WY TI Luteinizing hormone receptor mutations in disorders of sexual development and cancer SO PEDIATRIC PATHOLOGY & MOLECULAR MEDICINE LA English DT Review DE molecular endocrinology; luteinizing hormone receptor; activating; familial male-limited precocious puberty; inactivating; Leydig cell hypoplasia; male pseudohermaphroditism; amenorrhea; review ID LIMITED PRECOCIOUS PUBERTY; LEYDIG-CELL HYPOPLASIA; CONSTITUTIVELY ACTIVATING MUTATION; HUMAN LUTROPIN/CHORIOGONADOTROPIN RECEPTOR; HORMONE/CHORIONIC GONADOTROPIN RECEPTOR; PROTEIN-COUPLED RECEPTORS; 2 DIFFERENT PHENOTYPES; EXTRACELLULAR DOMAIN; CHORIOGONADOTROPIN RECEPTOR; MALE PSEUDOHERMAPHRODITISM AB Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea. C1 Georgetown Univ, Childrens Med Ctr, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Childrens Med Ctr, Dept Cell Biol, Washington, DC 20007 USA. Georgetown Univ, Childrens Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NICHHD, Ctr Res Mothers & Childrens, NIH, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chan, WY (reprint author), Georgetown Univ, Childrens Med Ctr, Dept Pediat, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 87 TC 1 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1522-7952 J9 PEDIATR PATHOL MOL M JI Pediatr. Pathol. Mol. Med. PD JAN-FEB PY 2000 VL 19 IS 1 BP 21 EP 40 PG 20 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 330JB UT WOS:000087958100002 ER PT J AU Stratakis, CA AF Stratakis, CA TI Genetics of Carney complex and related familial lentiginoses, and other multiple tumor syndromes SO PEDIATRIC PATHOLOGY & MOLECULAR MEDICINE LA English DT Review DE lentigines; myxoma; carney complex; multiple endocrine neoplasia; Peutz-Jeghers syndrome; Ruvalcaba-Myhre-Smith syndrome; LEOPARD syndrome; arterial dissections; genetics; review ID PEUTZ-JEGHERS-SYNDROME; SPOTTY SKIN PIGMENTATION; PSAMMOMATOUS MELANOTIC SCHWANNOMA; ADRENOCORTICAL NODULAR DYSPLASIA; LAUGIER-HUNZIKER SYNDROME; INCLUDING CARDIAC MYXOMA; AU-LAIT SPOTS; ENDOCRINE OVERACTIVITY; POLYPOSIS SYNDROMES; LEOPARD-SYNDROME AB Carney complex is a multiple endocrine neoplasia (MEN) syndrome that affects the adrenal cortex, the pituitary and thyroid glands, and the gonads. The complex is also associated with skin and mucosa pigmentation abnormalities and myxoid and other neoplasms of mesenchymal and neural crest origin. Thus, this syndrome also belongs to another group of genetic disorders, the lentiginoses (or lentigenoses), which include the Peutz-Jeghers, LEOPARD, arterial dissections and lentiginosis, and Laugier-Hunziker syndromes, Cowden disease and Ruvalcaba-Myhre-Smith (Bannayan-Zonana) syndrome and the centrofacial, benign patterned and segmental lentiginoses, all of which can be associated with a variety of developmental defects. The inheritance of Carney complex, just like that of the other MENs and the lentiginoses, is autosomal dominant. Genetic loci or genes have been identified for Carney complex, Peutz-Jeghers and Ruvalcaba-Myhre-Smith syndromes, but not for other lentiginoses. Elucidation of the molecular defects responsible for these disorders is expected to shed light on aspects of early neural crest differentiation, the regulation of pigmentation, the development of autonomous endocrine function, and endocrine and nonendocrine tumorigenesis. C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 128 TC 7 Z9 7 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1522-7952 J9 PEDIATR PATHOL MOL M JI Pediatr. Pathol. Mol. Med. PD JAN-FEB PY 2000 VL 19 IS 1 BP 41 EP 68 DI 10.1080/15227950050033765 PG 28 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 330JB UT WOS:000087958100003 ER PT J AU Vajo, Z Munnich, A AF Vajo, Z Munnich, A TI Coenzyme Q deficiency in two unrelated patients - Molecular studies SO PEDIATRIC PATHOLOGY & MOLECULAR MEDICINE LA English DT Article DE coenzyme Q ID UBIQUINONE BIOSYNTHESIS; SACCHAROMYCES-CEREVISIAE; MITOCHONDRIAL AB Coenzyme Q (CoQ) is a key lipid component in the mitochondrial respiratory chain. Unambiguous and severe CoQ deficiency associated with encephalomyopathy has been reported in only two patients. We tested both patients for mutations in the COQ7 cDNA, the only identified human gene involved in CoQ biosynthesis and show that their CoQ deficiency does not result from mutations in the COQ7 coding region. It is possible the CoQ deficiency in these individuals results from a mutation in another yet unidentified CoQ biosynthesis gene. C1 Necker Hosp, Gen Med Serv, Paris, France. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Vet Affairs Med Ctr, Phoenix, AZ 85012 USA. RP Vajo, Z (reprint author), Vet Affairs Med Ctr, 650 E Indian Sch Rd,111E, Phoenix, AZ 85012 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1522-7952 J9 PEDIATR PATHOL MOL M JI Pediatr. Pathol. Mol. Med. PD JAN-FEB PY 2000 VL 19 IS 1 BP 69 EP 72 PG 4 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 330JB UT WOS:000087958100004 ER PT J AU Anikster, Y Lucero, C Guo, JR Huizing, M Shotelersuk, V Bernardini, I McDowell, G Iwata, F Kaiser-Kupfer, MI Jaffe, R Thoene, J Schneider, JA Gahl, WA AF Anikster, Y Lucero, C Guo, JR Huizing, M Shotelersuk, V Bernardini, I McDowell, G Iwata, F Kaiser-Kupfer, MI Jaffe, R Thoene, J Schneider, JA Gahl, WA TI Ocular nonnephropathic cystinosis: Clinical, biochemical, and molecular correlations SO PEDIATRIC RESEARCH LA English DT Article ID SPLICE-SITE MUTATION; NEPHROPATHIC CYSTINOSIS; CYSTEAMINE THERAPY; RENAL-FUNCTION; GENE; TRANSPORT; PATIENT; COMPLICATIONS; INSUFFICIENCY; SUBSTITUTIONS AB Ocular nonnephropathic cystinosis, a variant of the classic nephropathic type of cystinosis, is an autosomal recessive lysosomal storage disorder characterized by photophobia due to corneal cystine crystals but absence of renal disease. We determined the molecular basis for ocular cystinosis in four individuals. All had mutations in the cystinosis gene CTNS, indicating that ocular cystinosis is allelic with classic nephropathic cystinosis. The ocular cystinosis patients each had one severe mutation and one mild mutation, the latter consisting of either a 928 G-->A (G197R) mutation or an IVS10-3 C-->G splicing mutation resulting in the insertion of 182 bp of IVS10 into the CTNS mRNA. The mild mutations appear to allow for residual CTNS mRNA production, significant amounts of lysosomal cystine transport, and lower levels of cellular cystine compared with those in nephropathic cystinosis. The lack of kidney involvement in ocular cystinosis may be explained by two different mechanisms. On the one hand (e.g. the G197R mutation), significant residual cystinosin activity may be present in every tissue. On the other hand (e.g. the IVS10-3 C-->G mutation), substantial cystinosin activity may exist in the kidney because of that tissue's specific expression of factors that promote splicing of a normal CTNS transcript. Each of these mechanisms could result in minimally reduced lysosomal cystine transport in the kidneys. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Clin Serv Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. RP Gahl, WA (reprint author), NICHD, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 39 TC 45 Z9 48 U1 2 U2 5 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2000 VL 47 IS 1 BP 17 EP 23 DI 10.1203/00006450-200001000-00007 PG 7 WC Pediatrics SC Pediatrics GA 268MD UT WOS:000084419400007 PM 10625078 ER PT J AU Uauy, R Mena, P Wegher, B Nieto, S Salem, N AF Uauy, R Mena, P Wegher, B Nieto, S Salem, N TI Long chain polyunsaturated fatty acid formation in neonates: Effect of gestational age and intrauterine growth SO PEDIATRIC RESEARCH LA English DT Article ID DOCOSAHEXAENOIC ACIDS; ARACHIDONIC-ACID; MAGNETIC-RESONANCE; VISUAL-ACUITY; INFANTS; BIRTH AB The present study was designed to evaluate the effect of gestational age and intrauterine growth on the long chain polyunsaturated fatty acid (LCP) synthesis from dietary precursors in neonates as reflected by plasma pools. These have been considered conditionally essential nutrients for normal growth, sensory maturation, and neurodevelopment. In vivo elongation/desaturation of deuterated d5-linoleic acid (d5-LA) to form arachidonic acid (AA), and d5-alpha-linolenic acid (d5-LNA) to form docosahexaenoic acid (DHA), was studied in 19 preterm appropriate-for-gestational-age (AGA) infants, 11 AGA term, and 11 intrauterine growth-retarded (IUGR) infants. They received a dose of 50 mg/kg body weight of d5-LA and d5-LNA enterally during the first days of life; d5-labeled derivatized fatty acids were determined in blood samples obtained at 24, 48, and 96 h after dosing. Lipids were extracted and fatty acids analyzed by gas chromatography and negative ion mass spectrometry. Mean concentrations, mu g/mL, and d5/d0 for n-3 and n-6 precursor and products were computed at various times and were also integrated over the complete study period. Significantly higher time-integrated concentration of d5-AA and d5-DHA were observed in preterm infants relative to the other two groups. Time-integrated enrichment of DHA relative to LNA was 100-fold lower in preterms, 410-fold lower in term, and 27-fold lower in IUGR infants. Similar significant declines in product to precursor enrichments were noted for the n-6 series. A significant negative correlation of AA and DHA formation based on time-integrated d5/d0 ratios with gestational age was noted; product/precursor enrichment versus gas chromatography for the n-6 series had an r of -0.5, p = 0.001, and for the n-3 series had an r of -0.6, p = 0.0001. Birth weight or weight adequacy did not add further strength to the relationship. We conclude that LCP formation from deuterated precursors occurs as early as 26 wk gestation, and in fact is more active at earlier gestational ages; growth retardation appears to slow down or diminish LCP formation. No quantitative estimates of LCP synthesis or nutritional sufficiency can be derived from these data. C1 Univ Chile, INTA, Santiago, Chile. Retina Fdn SW, Dallas, TX USA. NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. Hosp Sotero del Rio, Unidad Neonatol, Santiago, Chile. RP Uauy, R (reprint author), Univ Chile, INTA, Macul 5540,Casilla 138-11, Santiago, Chile. NR 32 TC 140 Z9 147 U1 0 U2 10 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD JAN PY 2000 VL 47 IS 1 BP 127 EP 135 DI 10.1203/00006450-200001000-00022 PG 9 WC Pediatrics SC Pediatrics GA 268MD UT WOS:000084419400022 PM 10625093 ER PT J AU Walsh-Sukys, MC Tyson, JE Wright, LL Bauer, CR Korones, SB Stevenson, DK Verter, J Stoll, BJ Lemons, JA Papile, LA Shankaran, S Donovan, EF Oh, W Ehrenkranz, RA Fanaroff, AA AF Walsh-Sukys, MC Tyson, JE Wright, LL Bauer, CR Korones, SB Stevenson, DK Verter, J Stoll, BJ Lemons, JA Papile, LA Shankaran, S Donovan, EF Oh, W Ehrenkranz, RA Fanaroff, AA TI Persistent pulmonary hypertension of the newborn in the era before nitric oxide: Practice variation and outcomes SO PEDIATRICS LA English DT Article DE pulmonary hypertension of the newborn; newborn; treatments; outcomes; practice variation ID EXTRACORPOREAL MEMBRANE-OXYGENATION; SEVERE RESPIRATORY-FAILURE; NEONATAL INTENSIVE-CARE; INFANTS; HYPERVENTILATION; MANAGEMENT; MORTALITY; PROSTATECTOMY; RATES AB Objectives. In the era before widespread use of inhaled nitric oxide, to determine the prevalence of persistent pulmonary hypertension (PPHN) in a multicenter cohort, demographic descriptors of the population, treatments used, the outcomes of those treatments, and variation in practice among centers. Study Design. A total of 385 neonates who received greater than or equal to 50% inspired oxygen and/or mechanical ventilation and had documented evidence of PPHN (2D echocardiogram or preductal or postductal oxygen difference) were tracked from admission at 12 Level III neonatal intensive care units. Demographics, treatments, and outcomes were documented. Results. The prevalence of PPHN was 1.9 per 1000 live births (based on 71 558 inborns) with a wide variation observed among centers (.43-6.82 per 1000 live births). Neonates with PPHN were admitted to the Level III neonatal intensive care units at a mean of 12 hours of age (standard deviation: 19 hours). Wide variations in the use of all treatments studied were found at the centers. Hyperventilation was used in 65% overall but centers ranged from 33% to 92%, and continuous infusion of alkali was used in 75% overall, with a range of 27% to 93% of neonates. Other frequently used treatments included sedation (94%; range: 77%-100%), paralysis (73%; range: 33%-98%), and inotrope administration (84%; range: 46%-100%). Vasodilator drugs, primarily tolazoline, were used in 39% (range: 13%-81%) of neonates. Despite the wide variation in practice, there was no significant difference in mortality among centers. Mortality was 11% (range: 4%-33%). No specific therapy was clearly associated with a reduction in mortality. To determine whether the therapies were equivalent, neonates treated with hyperventilation were compared with those treated with alkali infusion. Hyperventilation reduced the risk of extracorporeal membrane oxygenation without increasing the use of oxygen at 28 days of age. In contrast, the use of alkali infusion was associated with increased use of extracorporeal membrane oxygenation (odds ratio: 5.03, compared with those treated with hyperventilation) and an increased use of oxygen at 28 days of age. Conclusions. Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN. Randomized trials are needed to evaluate the role of these common therapies. C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NICHHD, Bethesda, MD 20892 USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Memphis, TN USA. Stanford Univ, Stanford, CA 94305 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Emory Univ, Atlanta, GA 30322 USA. Indiana Univ, Indianapolis, IN 46204 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Yale Univ, New Haven, CT USA. RP Walsh-Sukys, MC (reprint author), Rainbow Babies & Childrens Hosp, Room 3020,11100 Euclid Ave, Cleveland, OH 44106 USA. FU NICHD NIH HHS [U10HD21373, U10HD27851, U10HD27881] NR 27 TC 217 Z9 232 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2000 VL 105 IS 1 BP 14 EP 20 DI 10.1542/peds.105.1.14 PG 7 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400003 PM 10617698 ER PT J AU Pathomvanich, A Merke, DP Chrousos, GP AF Pathomvanich, A Merke, DP Chrousos, GP TI Early puberty: A cautionary tale SO PEDIATRICS LA English DT Editorial Material ID FUNCTIONAL OVARIAN HYPERANDROGENISM; PREMATURE PUBARCHE; GIRLS; HISTORY; HYPERINSULINEMIA; CHILDREN C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. US PHS, Washington, DC 20201 USA. RP Pathomvanich, A (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 12 TC 11 Z9 11 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2000 VL 105 IS 1 BP 115 EP 116 DI 10.1542/peds.105.1.115 PG 2 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400018 PM 10617713 ER PT J CA Comm Infect Dis TI Varicella vaccine update SO PEDIATRICS LA English DT Article ID HEALTHY-CHILDREN; UNITED-STATES; FOLLOW-UP; INFECTIONS; CHICKENPOX; VIRUS; EFFICACY AB Recommendations for routine varicella vaccination were published by the American Academy of Pediatrics in May 1995, but many eligible children remain unimmunized. This update provides additional information on the varicella disease burden before the availability of varicella vaccine, potential barriers to immunization, efforts to increase the level of coverage, new safety data, and new recommendations for use of the varicella vaccine after exposure and in children with human immunodeficiency virus infections. Pediatricians are strongly encouraged to support public health officials in the development and implementation of varicella immunization requirements for child care and school entry. C1 AAP Council Pediat Practice, Elk Grove Village, IL 60007 USA. Amer Thorac Soc, New York, NY 10019 USA. Canadian Paediat Soc, Ottawa, ON, Canada. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. Natl Vaccine Program Off, Rockville, MD USA. Columbia Univ, New York, NY 10027 USA. RP AAP Council Pediat Practice, Elk Grove Village, IL 60007 USA. NR 32 TC 2 Z9 8 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JAN PY 2000 VL 105 IS 1 BP 136 EP 141 PG 6 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400024 ER PT J CA Comm Infect Dis TI Prevention of Lyme disease SO PEDIATRICS LA English DT Article ID OUTER-SURFACE PROTEIN; BORRELIA-BURGDORFERI TRANSMISSION; NEW-YORK STATE; TICK BITES; ANTIBIOTIC-PROPHYLAXIS; RISK-FACTORS; NEW-JERSEY; VACCINE; OSPA; ARTHRITIS AB Lyme disease is currently the most frequently reported vector-borne illness in the United States, accounting for more than 95% of such cases. The purpose of this report is to provide recommendations for preventing Lyme disease, including the use of Lyme disease vaccine. Individuals can reduce their risk of Lyme disease by avoiding tick-infested habitats when in endemic areas. If exposure to tick-infested habitats cannot be avoided, individuals may reduce their risk of infection by using repellents, wearing protective clothing, and regularly checking for and removing attached ticks. Morbidity from Lyme disease can be reduced significantly by detecting and treating the infection in its early stages; early and appropriate treatment almost always results in a prompt and uncomplicated cure. A Lyme disease vaccine (LYMErix, SmithKline Beecham, Collegeville, PA) was licensed by the US Food and Drug Administration on December 21, 1998, for persons 15 to 70 years of age. This vaccine seems to be safe and effective, but whether its use is cost-effective has yet to be clearly established. Use of this vaccine causes false-positive enzyme immunoassay results for Lyme disease. Lyme disease can be diagnosed in vaccinated persons by immunoblot testing. Decisions about the use of this vaccine should be based on an assessment of a person's risk as determined by activities and behaviors relating to tick exposure in endemic areas. This vaccine should be considered an adjunct to, not a replacement for, the practice of personal protective measures against tick exposure and the early diagnosis and treatment of Lyme disease. C1 AAP Council Pediat Practice, Elk Grove Village, IL 60007 USA. Amer Thorac Soc, New York, NY 10019 USA. Canadian Paediat Soc, Ottawa, ON, Canada. Natl Vaccine Program Off, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 USA. RP Comm Infect Dis (reprint author), AAP Council Pediat Practice, Elk Grove Village, IL 60007 USA. NR 46 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2000 VL 105 IS 1 BP 142 EP 147 PG 6 WC Pediatrics SC Pediatrics GA 273KL UT WOS:000084706400025 ER EF