FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Halvorson, MJ Coligan, JE Sturmhofel, K AF Halvorson, MJ Coligan, JE Sturmhofel, K TI The vitronectin receptor (alpha V beta 3) as an example for the role of integrins in T lymphocyte stimulation SO IMMUNOLOGIC RESEARCH LA English DT Article DE vitronectin receptor; integrin; costimulation; T cell activation; outside-in signaling; gamma/delta T cell ID PROTEIN-TYROSINE KINASE; EXTRACELLULAR-MATRIX PROTEINS; CELL-ADHESION RECEPTORS; GROWTH FACTOR-BETA; TRANSMEMBRANE LINKAGE; FIBRONECTIN RECEPTOR; SIGNAL TRANSDUCTION; ACTIVATION ANTIGEN; GENE-EXPRESSION; LIGAND-BINDING AB Integrins are a family of cell surface receptors which mediate the adhesion of cells to each other or to extracellular matrix (ECM) proteins, The interaction of integrins with their ligands or counter-receptors was initially considered to be a one-way process in that cells actively regulate the interaction of integrins with their ligands ('inside-out signal'). In contrast, it was not obvious that cells would receive a signal from the outside via the integrin heterodimers following ligand binding ('outside-in signal'). Recent evidence increasingly supports the active role of integrins in cell activation and proliferation. Many reports describe the effects of integrin-mediated signaling in lymphoid cells, Our studies of gamma/delta T cells, expressing the beta 3 integrin vitronectin receptor (VNR), reflect some of the consequences this active interaction between lymphocytes and the ECM could have for T cell activation and differentiation. The VNR has been described as a T cell costimulatory molecule, We recently reported that the VNR has the potential to stimulate cytokine secretion in T cell hybridomas without involvement of T cell receptor-mediated signals. Further studies demonstrated tyrosine phosphorylation of proteins following VNR cross-linking and the interaction of the VNR with protein kinases, Intensive research focuses on the signal transduction mechanisms of integrins and their interaction with other costimulatory or activation molecules, This knowledge is important to better understand the role of adhesion molecules, the ECM, and the cellular microenvironment for lymphocyte activation and differentiation. C1 NIAID,NIH,MOLEC STRUCT LAB,ROCKVILLE,MD. NR 96 TC 13 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 1996 VL 15 IS 1 BP 16 EP 29 DI 10.1007/BF02918281 PG 14 WC Immunology SC Immunology GA UJ790 UT WOS:A1996UJ79000002 PM 8739562 ER PT J AU Gupta, D Singh, VK Rajasingh, J Shinohara, T Misra, R Agarwal, SS AF Gupta, D Singh, VK Rajasingh, J Shinohara, T Misra, R Agarwal, SS TI Cellular immune responses of patients with juvenile chronic arthritis to retinal antigens and their synthetic peptides SO IMMUNOLOGIC RESEARCH LA English DT Article DE juvenile chronic arthritis; peptide M; peptide G; retinal S-antigen; histone H3 peptide ID EXPERIMENTAL AUTOIMMUNE UVEITIS; LYMPHOCYTE CROSS-REACTION; BOVINE S-ANTIGEN; MOLECULAR MIMICRY; UVEITOPATHOGENIC SITE; RHEUMATOID-ARTHRITIS; ANTINUCLEAR ANTIBODIES; SEQUENCE HOMOLOGY; BINDING PROTEIN; DISEASE AB The objective of this study was to determine the proliferative responses of peripheral blood lymphocytes of ocular antigens like retinal S-antigen, peptides M and G of S-antigen, yeast histone H3 peptide 106-121 homologous to peptide M and peptide R16 of interphotoreceptor retinoid binding protein (IRBP) in children with juvenile chronic arthritis (JCA). We have studied the in vitro proliferative response of peripheral blood lymphocytes from 41 patients with JCA (10 with and 31 without uveitis) and 23 healthy controls against the above antigens, The responders were retested after 1 or 6 months. Fifty (5/10) and 9.7% (3/31) of JCA patients with and without uveitis, respectively, responded (stimulation index > 3) to S-antigen or one of its peptide listed above or yeast histone H3 peptide or R16 of IRBP, None of the healthy controls responded to ally of these antigens, The difference in the frequency of responders (SI > 3) between JCA associated with uveitis and healthy controls was statistically significant (p = 0.001), Similarly, the difference between JCA with and without uveitis was also significant (p = 0.013), Our findings suggest that these antigens may have a role in the pathogenesis of uveitis in a subset of patients with JCA. C1 NEI,LRCMB,MOLEC BIOL SECT,NIH,BETHESDA,MD 20892. SANJAY GANDHI POSTGRAD INST MED SCI,DEPT IMMUNOL,LUCKNOW,UTTAR PRADESH,INDIA. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 35 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 1996 VL 15 IS 1 BP 74 EP 83 DI 10.1007/BF02918285 PG 10 WC Immunology SC Immunology GA UJ790 UT WOS:A1996UJ79000006 PM 8739566 ER PT J AU Kawakami, Y Rosenberg, SA AF Kawakami, Y Rosenberg, SA TI T-cell recognition of self peptides as tumor rejection antigens SO IMMUNOLOGIC RESEARCH LA English DT Article DE tumor antigens; melanoma; MART-1; self antigens; T lymphocytes; MHC binding motif; tolerance, immunologic; epitopes, dominance and crypticity; autoimmunity; immunotherapy ID HUMAN-MELANOMA ANTIGENS; INFILTRATING LYMPHOCYTES; IN-VITRO; IMMUNODOMINANT PEPTIDE; MULTIPLE EPITOPES; PERIPHERAL-BLOOD; ANCHOR RESIDUES; IDENTIFICATION; CTL; IMMUNOTHERAPY AB Human melanoma antigens and their epitopes recognized by T cells have recently been identified. HLA-A2 binding epitopes of melanoma antigens MART-1 and gp100 were characterized and suspected to be subdominant/cryptic self determinants. Together with other findings of tumor-specific mutated self peptides as tumor antigens recognized by T cells, the nature of the antitumor immune response to human melanoma has been revealed at a molecular level. These findings have implications not only for understanding of the immune response to self peptides in normal and pathologic conditions, but also for the development of immunotherapies for cancer and autoimmune diseases. RP Kawakami, Y (reprint author), NCI,SURG BRANCH,SB,COP,DCT,NIH,BLDG 10,RM 2B42,10 CTR DR,MSC-1502,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 51 TC 44 Z9 45 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 1996 VL 15 IS 3 BP 179 EP 190 DI 10.1007/BF02918248 PG 12 WC Immunology SC Immunology GA VK663 UT WOS:A1996VK66300001 PM 8902575 ER PT J AU Singh, VK Nagaraju, K AF Singh, VK Nagaraju, K TI Experimental autoimmune uveitis: Molecular mimicry and oral tolerance SO IMMUNOLOGIC RESEARCH LA English DT Review DE uveitis, experimental autoimmune; molecular mimicry; oral tolerance; autoantigens ID MYELIN BASIC-PROTEIN; RETINAL S-ANTIGEN; T-CELL-RECEPTOR; INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; EXPERIMENTAL ALLERGIC UVEITIS; DELAYED-TYPE HYPERSENSITIVITY; NATURAL SUPPRESSOR CELLS; HEAT-SHOCK PROTEIN; GROWTH-FACTOR-BETA; IMMUNE-RESPONSES AB Intraocular inflammatory disease or uveitis, which affects the uveal tract and the retina of the eyes in human, is the major cause of visual impairment. Experimental autoimmune uveitis (EAU) is a T-cell-mediated autoimmune disease directed against retinal proteins and has been studied in several mammalian species including subhuman primates as a model for human posterior uveitis. Autoimmune responses provoked by molecular mimicry occur when the nonself and host determinants are similar enough to cross-react yet different enough to break immunological tolerance, and is one of the proposed mechanisms for induction of autoimmune diseases. Therapeutic immunomodulatory strategies have been used to induce antigen-specific peripheral immune tolerance in animal models of T-cell-mediated autoimmune diseases by oral administration of autoantigens. Oral tolerance leads to unique mechanisms of tissue and disease-specific immunosuppression, which would circumvent the immunotherapeutic problem of multiple target tissue autoreactivity. Several groups have investigated the effects of delivering autoantigens across gastric mucosal surfaces. This review briefly discusses molecular mimicry and the mechanism of induction of oral tolerance with respect to immunopathogenesis of T-cell-mediated autoimmune diseases in general and EAU in particular. C1 SANJAY GANDHI POSTGRAD INST MED SCI,DEPT IMMUNOL,LUCKNOW,UTTAR PRADESH,INDIA. NIAMSD,CONNECT TISSUE DIS SECT,ARTHRITIS & RHEUMATISM BRANCH,NIH,BETHESDA,MD. NR 179 TC 11 Z9 11 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 1996 VL 15 IS 4 BP 323 EP 346 DI 10.1007/BF02935316 PG 24 WC Immunology SC Immunology GA WB494 UT WOS:A1996WB49400005 PM 8988399 ER PT J AU Duchmann, R Jaffe, J Ehrhardt, R Alling, DW Strober, W AF Duchmann, R Jaffe, J Ehrhardt, R Alling, DW Strober, W TI Differential usage of T-cell receptor v beta gene families by CD4(+) and CD8(+) T cells in patients with CD8(hi) common variable immunodeficiency: Evidence of a post-thymic effect SO IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; CD8+; EXPRESSION; SEGMENTS; SUBSETS; DISEASE; CD4+ AB In this study, we report that differences between T-cell receptor (TCR) V beta gene family usage in CD4(+) and CD8(+) T cells are significantly greater in a subgroup of patients with common variable immunodeficiency (CVI) and high levels of activated CD8(+) T cells (CD8(hi) CVI) than in controls (P < 0.001). In CD8(hi) CVI patients, such differences were also significantly greater for V beta 12 than for other V beta families. As the causes of the differential usage of V beta gene families by CD4(+) and CD8(+) T cells are under investigation, it was interesting that the combined differences between V beta gene family usage in the CD4(+) and CD8(+) T-cell subpopulations as a whole were significantly lower than the combined differences between individual V beta gene family usage in either CD4(+) or CD8(+) T-cell subpopulations (P < 0.001 in both control and CD8(hi) CVI patients). Further, the pattern of V beta gene family usage in CD4(+) T cells was remarkably similar to that in CD8(+) T cells in both groups. These data strongly suggest that differences in V beta gene family usage arising from coselection by major histocompatibility complex (MHC) class I versus MHC class II restriction elements do not fundamentally distort 'basic' V beta gene family usage patterns. They also support the concept that differences in CD4(+) and CD8(+) T-cell V beta gene family usage, which were increased in CD8(hi) CVI, can arise from high-affinity interactions between disease-associated antigens or superantigens and T cells in the post-thymic T-cell compartment. C1 UNIV MAINZ,DEPT INTERNAL MED 1,W-6500 MAINZ,GERMANY. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NIAID,OFF DIRECTOR INTRAMURAL RES,BETHESDA,MD 20892. NR 28 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JAN PY 1996 VL 87 IS 1 BP 99 EP 107 PG 9 WC Immunology SC Immunology GA TQ489 UT WOS:A1996TQ48900015 PM 8666443 ER PT S AU Felix, K Janz, S Pitha, J Williams, JA Mushinski, EB Bornkamm, GW Potter, M AF Felix, K Janz, S Pitha, J Williams, JA Mushinski, EB Bornkamm, GW Potter, M BE Potter, M Rose, NR TI Cytotoxicity and membrane damage in vitro by inclusion complexes between gamma-cyclodextrin and siloxanes SO IMMUNOLOGY OF SILICONES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on the Immunology of Silicones CY MAR 13-14, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD HO NIH, NATCHER CONF CTR AB Inclusion complexes of gamma-cyclodextrin and octamethylcyclotetrasiloxane (D4), decamethyltetrasiloxane (M10TS), and 1,3,5,7-tetramethyltetravinylcyclotetra-siloxane (TMTV-D4) were prepared to compare the cytotoxic effects of siloxanes in vitro. In these preparations, the hydrophobic siloxanes are surrounded by a hydrophilic shell of eight circularly linked D-glucose molecules (gamma-cyclodextrin), and upon contact with plasma membranes the siloxane molecule can intercalate into the lipid bilayer of the cell membrane. XRPC24, 2-11 plasmacytoma, CH12.LX lymphoma and P388D1 macrophage-like cells were used as indicator cells in toxicity assays. Using an MTT tetrazolium reduction to formazan test, a colorimetric method to determine the number of viable cells, the 50% minimal lethal doses (CD50) for the siloxane compounds were found to range from 30 to 50 mu M. Sublethal doses (e.g., 15 mu M and lower) resulted in the loss oi lactate dehydrogenase (LDH) and glutathione (GSH) from the cytosolic compartment of the target cells and thus indicated cytotoxicity. Treatment of macrophages with siloxanes resulted in a higher production of interleukin-6 (IL-6) than was exhibited by untreated macrophages. The B9 cell bioassay of these treated cells showed as much as a 10 fold higher production (500 U/ml) of TL-h than did the untreated cells. The degree of increase was dependent on the compound and concentration used. The results of this study show that low molecular weight siloxanes produce lethal effects on B-lymphocyte derived target cells in vitro and permeabilize the plasma membranes at lower sublethal concentrations. C1 NCI,GENET LAB,NIH,BETHESDA,MD 20892. NIA,MACROMOL CHEM SECT,NIH,BALTIMORE,MD. NIH,IMMUNOL LAB,FDA,BETHESDA,MD 20892. RP Felix, K (reprint author), GSF MUNICH,INST KLIN MOL BIOL & TUMORGENET,HAMATOLOGIKUM,MUNICH,GERMANY. NR 13 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60272-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 210 BP 93 EP 99 PG 7 WC Immunology; Microbiology SC Immunology; Microbiology GA BF83W UT WOS:A1996BF83W00010 PM 8565593 ER PT S AU Alving, CR Wassef, NM Potter, M AF Alving, CR Wassef, NM Potter, M BE Potter, M Rose, NR TI Antibodies to cholesterol: Biological implications of antibodies to lipids SO IMMUNOLOGY OF SILICONES SE Current Topics in Microbiology and Immunology LA English DT Review CT Workshop on the Immunology of Silicones CY MAR 13-14, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD HO NIH, NATCHER CONF CTR ID SILICONE-GEL; LIPOSOMES; BINDING; PHOSPHOLIPIDS; GLYCOLIPIDS AB Injection of silicone gel or silicone oil intraperitoneally into BALB/c mice induced the formation of antibodies that reacted by ELISA with highly purified crystalline cholesterol and, to a much lesser extent, antibodies that reacted with a phospholipid (dimyristoyl phosphatidylglycerol). Although IgM and IgG antibodies to cholesterol were detected, the titers of IgG antibodies were low when compared with IgM. The titers of IgM antibodies to cholesterol in certain sera exhibited activities that reached baseline values at dilutions as high as 1:5000, thus making them equivalent to titers that have been previously published for ascites fluid containing murine monoclonal antibodies to cholesterol. The antibodies to cholesterol induced by silicone compounds are indistinguishable in their binding to crystalline cholesterol from naturally-occurring antibodies to cholesterol in normal human serum. They are also indistiguishable from antibodies induced by a proposed vaccine to cholesterol that is currently in late preclinical development for prevention of hypercholesterolemia in humans. The anti-cholesterol vaccine, which consists of liposomes heavily laden with cholesterol as an antigen and lipid A as an adjuvant, induces antibodies that react with low density lipoproteins (LDL) and opsonize them for removal by liver macrophages. It appears that silicone gel or silicone oil causes recruitment and adsorption of cholesterol at the injection site, and also serves as an adjuvant that may have immunostimulant properties similar to lipid A for inducing antibodies to lipids. Antibodies to lipids such as cholesterol or phospholipids are not harmful to intact cell membranes because of steric hindrance from surrounding lipids and larger macromolecules that block binding of the antibodies. C1 NCI, GENET LAB, DCBDC, NIH, BETHESDA, MD 20892 USA. RP Alving, CR (reprint author), WALTER REED ARMY INST RES, DEPT MEMBRANE BIOCHEM, WASHINGTON, DC 20307 USA. NR 19 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-60272-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 210 BP 181 EP 186 PG 6 WC Immunology; Microbiology SC Immunology; Microbiology GA BF83W UT WOS:A1996BF83W00018 PM 8565556 ER PT S AU OHanlon, TP Okada, S Love, LA Dick, G Young, VL Miller, FW AF OHanlon, TP Okada, S Love, LA Dick, G Young, VL Miller, FW BE Potter, M Rose, NR TI Immunohistopathology and T cell receptor gene expression in capsules surrounding silicone breast implants SO IMMUNOLOGY OF SILICONES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on the Immunology of Silicones CY MAR 13-14, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD HO NIH, NATCHER CONF CTR ID MUSCLE-INFILTRATING LYMPHOCYTES; GEL; DISEASE C1 US FDA,CTR FOOD SAFETY & APPL NUTR,CLIN RES & REVIEW STAFF,WASHINGTON,DC 20204. NIH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DIV PLAST SURG,ST LOUIS,MO 63110. RP OHanlon, TP (reprint author), US FDA,CTR BIOL EVALUAT & RES,MOL IMMUNOL LAB,BETHESDA,MD 20892, USA. OI Miller, Frederick/0000-0003-2831-9593 NR 17 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60272-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 210 BP 237 EP 242 PG 6 WC Immunology; Microbiology SC Immunology; Microbiology GA BF83W UT WOS:A1996BF83W00023 PM 8565561 ER PT S AU Rabkin, CS Silverman, S Tricot, G Garland, LL Ballester, O Potter, M AF Rabkin, CS Silverman, S Tricot, G Garland, LL Ballester, O Potter, M BE Potter, M Rose, NR TI The national cancer institute silicone implant/multiple myeloma registry SO IMMUNOLOGY OF SILICONES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on the Immunology of Silicones CY MAR 13-14, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD HO NIH, NATCHER CONF CTR C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90211. UNIV ARKANSAS MED SCI HOSP,LITTLE ROCK,AR 72205. UNIV S FLORIDA,H LEE MOFFITT CANC CTR,COLL MED,TAMPA,FL 33612. NCI,GENET LAB,BETHESDA,MD 20892. RP Rabkin, CS (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 5 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60272-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 210 BP 385 EP 387 PG 3 WC Immunology; Microbiology SC Immunology; Microbiology GA BF83W UT WOS:A1996BF83W00041 PM 8565581 ER PT S AU Potter, M Morrison, S AF Potter, M Morrison, S BE Potter, M Rose, NR TI Plasmacytoma development in mice injected with silicone gels SO IMMUNOLOGY OF SILICONES SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on the Immunology of Silicones CY MAR 13-14, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD HO NIH, NATCHER CONF CTR ID MILKY SPOTS; C-MYC; INDUCTION; PRISTANE; SUSCEPTIBILITY; RECOMBINATIONS; GENES RP Potter, M (reprint author), NCI,GENET LAB,DCBDC,NIH,BETHESDA,MD 20892, USA. NR 20 TC 11 Z9 11 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60272-0 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 210 BP 397 EP 407 PG 11 WC Immunology; Microbiology SC Immunology; Microbiology GA BF83W UT WOS:A1996BF83W00043 PM 8565584 ER PT J AU Shearer, GM Clerici, M AF Shearer, GM Clerici, M TI Protective immunity against HIV infection: Has nature done the experiment for us? SO IMMUNOLOGY TODAY LA English DT Article ID RESPONSES; IMMUNIZATION; INDIVIDUALS; LYMPHOCYTES; VACCINATION; PARTNERS; ANTIGENS; CHILDREN; EXPOSURE; STRATEGY AB Numerous reports indicate that human immunodeficiency virus (HIV)-exposed individuals from several high-risk groups remain seronegative but exhibit strong HIV-specific cell-mediated immunity. Here, Gene Shearer and Mario Clerici postulate that a potent cellular response can be protective against HIV infection and speculate on the significance of these data with respect to the development of vaccines. C1 UNIV MILAN,CATTEDRA IMMUNOL,I-20133 MILAN,ITALY. RP Shearer, GM (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 169 Z9 170 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JAN PY 1996 VL 17 IS 1 BP 21 EP 24 DI 10.1016/0167-5699(96)80564-0 PG 4 WC Immunology SC Immunology GA TQ015 UT WOS:A1996TQ01500011 PM 8652046 ER PT J AU Morse, HC AF Morse, HC TI Molecular mimicry: CLIP, MHC class II supermotifs and MAIDS SO IMMUNOLOGY TODAY LA English DT Letter ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; MICE RP Morse, HC (reprint author), NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JAN PY 1996 VL 17 IS 1 BP 47 EP 48 DI 10.1016/0167-5699(96)80569-X PG 2 WC Immunology SC Immunology GA TQ015 UT WOS:A1996TQ01500017 PM 8652054 ER PT J AU Hornstein, EH Vassilopoulos, D Thomas, DE Friedman, FK Tsokos, GC AF Hornstein, EH Vassilopoulos, D Thomas, DE Friedman, FK Tsokos, GC TI Modulation of human T-lymphocyte plasma membrane Ca+2 permeability by imidazole antimycotics. SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article ID INTRACELLULAR CA2+ STORES; CELL ANTIGEN RECEPTOR; CA-2+ INFLUX; CALCIUM; CYTOCHROME-P-450; INHIBITION; MOBILIZATION; THAPSIGARGIN; ACTIVATION; AGENTS AB The role of cytochrome P-450 in the regulation of plasma membrane Ca+2 permeability of human peripheral T-lymphocytes by intracellular Ca+2 was examined. We assessed the effect of imidazole inhibitors of cytochrome P-450 on the intracytoplasmic free Ca+2 ([Ca+2]i) response generated using the microsomal ATPase inhibitor thapsigargin (THG) to deplete the intracellular Ca+2 stores. Econazole, miconazole and clotrimazole dramatically inhibited the THG mediated increase in [Ca-2]i and induced an increase in [Ca+2]i themselves. This inhibitory effect was previously observed in other cell systems and was attributed to inhibition of cytochrome P-450 by these agents. However, we evaluated a variety of structurally dissimilar P-450 inhibitors and found that none affected [Ca+2]i, indicating that the mechanism of imidazole action does not involve P-450. C1 WALTER REED ARMY MED CTR,DEPT MED,WASHINGTON,DC 20307. NCI,MOLEC CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. WALTER REED ARMY INST RES,DEPT CLIN PHYSIOL,WASHINGTON,DC 20307. RP Hornstein, EH (reprint author), WALTER REED ARMY MED CTR,DEPT CLIN INVEST,WASHINGTON,DC 20307, USA. RI Friedman, Fred/D-4208-2016 NR 23 TC 6 Z9 6 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0892-3973 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PY 1996 VL 18 IS 2 BP 237 EP 245 DI 10.3109/08923979609052734 PG 9 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA UP002 UT WOS:A1996UP00200005 PM 8771369 ER PT S AU Bacon, CM Cho, SS O'Shea, JJ AF Bacon, CM Cho, SS O'Shea, JJ BE Lotze, MT Trinchieri, G Gately, M Wolf, S TI Signal transduction by interleukin-12 and interleukin-2 - A comparison and contrast SO INERLEUKIN 12: CELLULAR AND MOLECULAR IMMUNOLOGY OF AN IMPORTANT REGULATORY CYTOKINE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Interleukin-12 - Cellular and Molecular Immunology of an Important Regulatory Cytokine CY NOV 09-12, 1995 CL NEW YORK, NEW YORK SP New York Acad Sci, Genet Inst Inc, Hoffmann La Roche Inc, Boehringer Ingelheim Pharm Inc, Bristol Myers Squibb Pharm Res Inst, Lab Line Instruments Inc, Merck & Co Inc, NCI, Pfizer Inc, Upjohn Co, SmithKline Beecham Pharm, Wyeth Ayerst Res ID RECEPTOR-GAMMA-CHAIN; PROTEIN-TYROSINE KINASE; SEVERE COMBINED IMMUNODEFICIENCY; DEFECTIVE LYMPHOID DEVELOPMENT; NATURAL-KILLER-CELLS; HUMAN GROWTH-HORMONE; DNA-BINDING ACTIVITY; JAK-3 JANUS KINASE; HUMAN T-CELLS; IL-2 RECEPTOR C1 NIAMSD, Arthrit & Rheumatism Branch, Lymphocyte Cell Biol Sect, NIH, Bethesda, MD 20892 USA. RP Bacon, CM (reprint author), NIAMSD, Arthrit & Rheumatism Branch, Lymphocyte Cell Biol Sect, NIH, Bldg 10,Room 9N262,10 CTR DR MSC 1820, Bethesda, MD 20892 USA. NR 106 TC 11 Z9 11 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 1-57331-018-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 795 BP 41 EP 59 DI 10.1111/j.1749-6632.1996.tb52654.x PG 19 WC Biochemistry & Molecular Biology; Cell Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Immunology; Science & Technology - Other Topics GA BK04A UT WOS:000070968300006 PM 8958916 ER PT S AU Kelsall, BL Stuber, E Neurath, M Strober, W AF Kelsall, BL Stuber, E Neurath, M Strober, W BE Lotze, MT Trinchieri, G Gately, M Wolf, S TI Interleukin-12 production by dendritic cells - The role of CD40-CD40L interactions in Th1 T-cell responses SO INERLEUKIN 12: CELLULAR AND MOLECULAR IMMUNOLOGY OF AN IMPORTANT REGULATORY CYTOKINE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Interleukin-12 - Cellular and Molecular Immunology of an Important Regulatory Cytokine CY NOV 09-12, 1995 CL NEW YORK, NEW YORK SP New York Acad Sci, Genet Inst Inc, Hoffmann La Roche Inc, Boehringer Ingelheim Pharm Inc, Bristol Myers Squibb Pharm Res Inst, Lab Line Instruments Inc, Merck & Co Inc, NCI, Pfizer Inc, Upjohn Co, SmithKline Beecham Pharm, Wyeth Ayerst Res ID ANTIBODY; LIGAND; CD40; GP39 C1 NIAID, Clin Invest Lab, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. RP Kelsall, BL (reprint author), NIAID, Clin Invest Lab, Mucosal Immun Sect, NIH, Bldg 10,11N238,10 Ctr Dr, Bethesda, MD 20892 USA. NR 19 TC 116 Z9 119 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 1-57331-018-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 795 BP 116 EP 126 DI 10.1111/j.1749-6632.1996.tb52660.x PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Immunology; Science & Technology - Other Topics GA BK04A UT WOS:000070968300012 PM 8958922 ER PT S AU Sher, A Jankovic, D Cheever, A Wynn, T AF Sher, A Jankovic, D Cheever, A Wynn, T BE Lotze, MT Trinchieri, G Gately, M Wolf, S TI An IL-12-based vaccine approach for preventing immunopathology in schistosomiasis SO INERLEUKIN 12: CELLULAR AND MOLECULAR IMMUNOLOGY OF AN IMPORTANT REGULATORY CYTOKINE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Interleukin-12 - Cellular and Molecular Immunology of an Important Regulatory Cytokine CY NOV 09-12, 1995 CL NEW YORK, NEW YORK SP New York Acad Sci, Genet Inst Inc, Hoffmann La Roche Inc, Boehringer Ingelheim Pharm Inc, Bristol Myers Squibb Pharm Res Inst, Lab Line Instruments Inc, Merck & Co Inc, NCI, Pfizer Inc, Upjohn Co, SmithKline Beecham Pharm, Wyeth Ayerst Res ID INTERFERON-GAMMA PRODUCTION; CELL STIMULATORY FACTOR; CD4+ T-CELLS; IFN-GAMMA; LEISHMANIA-MAJOR; MESSENGER-RNA; MANSONI; IL-12; INTERLEUKIN-12; TH1 C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sher, A (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126, Bethesda, MD 20892 USA. NR 22 TC 22 Z9 22 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 1-57331-018-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 795 BP 202 EP 207 DI 10.1111/j.1749-6632.1996.tb52669.x PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Immunology; Science & Technology - Other Topics GA BK04A UT WOS:000070968300021 PM 8958931 ER PT S AU Brunda, MJ Luistro, L Rumennik, L Wright, RB Wigginton, JM Wiltrout, RH Hendrzak, JA Palleroni, AV AF Brunda, MJ Luistro, L Rumennik, L Wright, RB Wigginton, JM Wiltrout, RH Hendrzak, JA Palleroni, AV BE Lotze, MT Trinchieri, G Gately, M Wolf, S TI Interleukin-12: Murine models of a potent antitumor agent SO INERLEUKIN 12: CELLULAR AND MOLECULAR IMMUNOLOGY OF AN IMPORTANT REGULATORY CYTOKINE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Interleukin-12 - Cellular and Molecular Immunology of an Important Regulatory Cytokine CY NOV 09-12, 1995 CL NEW YORK, NEW YORK SP New York Acad Sci, Genet Inst Inc, Hoffmann La Roche Inc, Boehringer Ingelheim Pharm Inc, Bristol Myers Squibb Pharm Res Inst, Lab Line Instruments Inc, Merck & Co Inc, NCI, Pfizer Inc, Upjohn Co, SmithKline Beecham Pharm, Wyeth Ayerst Res ID NATURAL-KILLER-CELLS; IFN-GAMMA PRODUCTION; T-CELLS; IN-VIVO; TUMOR-REGRESSION; INTERFERON-GAMMA; RECOMBINANT IL-12; EXPRESSION; CYTOKINE; MICE C1 Hoffmann La Roche Inc, Dept Oncol, Nutley, NJ 07110 USA. SAIC Frederick, Biol Carcinogenesis & Dev Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Brunda, MJ (reprint author), Hoffmann La Roche Inc, Dept Oncol, 340 Kingsland St, Nutley, NJ 07110 USA. NR 48 TC 26 Z9 26 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-018-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 795 BP 266 EP 274 DI 10.1111/j.1749-6632.1996.tb52676.x PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Immunology; Science & Technology - Other Topics GA BK04A UT WOS:000070968300028 PM 8958938 ER PT S AU Neurath, MF Fuss, I Kelsall, B Zum Buschenfelde, KHM Strober, W AF Neurath, MF Fuss, I Kelsall, B Zum Buschenfelde, KHM Strober, W BE Lotze, MT Trinchieri, G Gately, M Wolf, S TI Effects of IL-12 and antibodies to IL-12 on established granulomatous colitis in mice SO INERLEUKIN 12: CELLULAR AND MOLECULAR IMMUNOLOGY OF AN IMPORTANT REGULATORY CYTOKINE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Interleukin-12 - Cellular and Molecular Immunology of an Important Regulatory Cytokine CY NOV 09-12, 1995 CL NEW YORK, NEW YORK SP New York Acad Sci, Genet Inst Inc, Hoffmann La Roche Inc, Boehringer Ingelheim Pharm Inc, Bristol Myers Squibb Pharm Res Inst, Lab Line Instruments Inc, Merck & Co Inc, NCI, Pfizer Inc, Upjohn Co, SmithKline Beecham Pharm, Wyeth Ayerst Res ID INFLAMMATORY BOWEL-DISEASE; ULCERATIVE-COLITIS C1 NIAID, Mucosal Immun Sect, LCI, NIH, Bethesda, MD 20892 USA. RP Neurath, MF (reprint author), NIAID, Mucosal Immun Sect, LCI, NIH, Bldg 10,Room 11N238,Rockville Pike, Bethesda, MD 20892 USA. NR 9 TC 31 Z9 31 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 1-57331-018-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 795 BP 368 EP 370 DI 10.1111/j.1749-6632.1996.tb52695.x PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Immunology; Science & Technology - Other Topics GA BK04A UT WOS:000070968300047 PM 8958957 ER PT S AU Wigginton, JM Komschlies, KL Green, JE Cox, GW Jorcyk, CL Back, TC Franco, JL Brunda, MJ Wiltrout, RH AF Wigginton, JM Komschlies, KL Green, JE Cox, GW Jorcyk, CL Back, TC Franco, JL Brunda, MJ Wiltrout, RH BE Lotze, MT Trinchieri, G Gately, M Wolf, S TI Evaluation of the antitumor activity of the interleukin-12 pulse interleukin-2 combination SO INERLEUKIN 12: CELLULAR AND MOLECULAR IMMUNOLOGY OF AN IMPORTANT REGULATORY CYTOKINE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Interleukin-12 - Cellular and Molecular Immunology of an Important Regulatory Cytokine CY NOV 09-12, 1995 CL NEW YORK, NEW YORK SP New York Acad Sci, Genet Inst Inc, Hoffmann La Roche Inc, Boehringer Ingelheim Pharm Inc, Bristol Myers Squibb Pharm Res Inst, Lab Line Instruments Inc, Merck & Co Inc, NCI, Pfizer Inc, Upjohn Co, SmithKline Beecham Pharm, Wyeth Ayerst Res ID CELL STIMULATORY FACTOR; NATURAL-KILLER-CELLS; NK-CELLS; T-CELLS; IL-12; EXPRESSION; RESPONSES; PROLIFERATION; LYMPHOCYTES; SYNERGIZES C1 SAIC Frederick, Biol Carcinogenesis & Dev Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Oncol Mol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Expt Immunol Lab, Frederick, MD 21702 USA. Hoffmann La Roche Inc, Dept Oncol, Nutley, NJ 07110 USA. RP Wigginton, JM (reprint author), SAIC Frederick, Biol Carcinogenesis & Dev Program, Frederick, MD 21702 USA. NR 18 TC 8 Z9 8 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 1-57331-018-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 795 BP 434 EP 439 DI 10.1111/j.1749-6632.1996.tb52714.x PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Immunology; Science & Technology - Other Topics GA BK04A UT WOS:000070968300066 PM 8958976 ER PT J AU Bosworth, BT Samuel, JE Moon, HW OBrien, AD Gordon, VM Whipp, SC AF Bosworth, BT Samuel, JE Moon, HW OBrien, AD Gordon, VM Whipp, SC TI Vaccination with genetically modified Shiga-like toxin IIe prevents edema disease in swine SO INFECTION AND IMMUNITY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; ESCHERICHIA-COLI O157-H7; TRANSFER RNA-BINDING; HEMORRHAGIC COLITIS; CALF DIARRHEA; CYTO-TOXIN; SLT-IIV; PIGS; STRAINS; RIBOSOMES AB Escherichia coli strains producing Shiga-like toxin II variant (SLT-IIe, formerly called SLT-IIv) cause edema disease in weaned pigs, Vaccination of pigs with a genetically modified form of Shiga like toxin IIe, SLT-IIe(E167Q), has been previously shown to he nontoxic and to induce antibodies to SLT-IIe (V. M. Gordon, S. C. Whipp, H. W. Moon, A. D. O'Brien, and J. E. Samuel, Infect. Immun. 60:485-502, 1992), Fifty micrograms of SLT-IIe(E167Q) toxin was used to vaccinate suckling pigs at 1 and 2 weeks of age, Both vaccinated and nonvaccinated pigs were orally inoculated with an SLT-IIe-producing strain of E. coli after weaning (3 to 4 weeks of age). Pigs fed a low-protein diet that were not vaccinated with SLT-IIe(E167Q) developed subclinical edema disease, histologically evident as vascular necrosis, Pigs fed a high-protein diet that were not vaccinated with SLT-IIe(E167Q) developed clinical edema disease manifested as vascular necrosis, reduced weight gain, ataxia, palpebral edema, lateral recumbency, and death, Pigs vaccinated with SLT-IIe(E167Q) had a reduction in the incidence of subclinical edema disease and never developed clinical edema disease. These data demonstrate that vaccination with a genetically modified form of SLT-IIe prevents edema disease and are consistent with the notion that diet influences susceptibility to edema disease. C1 TEXAS A&M UNIV,COLL MED,DEPT MED MICROBIOL & IMMUNOL,COLLEGE STN,TX 77843. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. RP Bosworth, BT (reprint author), USDA ARS,NATL ANIM DIS CTR,PHYSIOPATHOL RES UNIT,POB 70,AMES,IA 50010, USA. NR 38 TC 40 Z9 47 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 1996 VL 64 IS 1 BP 55 EP 60 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TM718 UT WOS:A1996TM71800009 PM 8557374 ER PT J AU Schwan, WR Kugler, S Schuller, S Kopecko, DJ Goebel, W AF Schwan, WR Kugler, S Schuller, S Kopecko, DJ Goebel, W TI Detection and characterization by differential PCR of host eukaryotic cell genes differentially transcribed following uptake of intracellular bacteria SO INFECTION AND IMMUNITY LA English DT Article ID POLYMERASE CHAIN-REACTION; LISTERIA-MONOCYTOGENES; MESSENGER-RNA; SALMONELLA-TYPHIMURIUM; SIGNAL-TRANSDUCTION; MAMMALIAN-CELLS; PROTEIN; EXTRACTION; EXPRESSION; SEQUENCE AB Host eukaryotic cell genes that are differentially transcribed after phagocytosis of various pathogenic and nonpathogenic bacterial cells were identified by a differential PCR (DPCR) system, This DPCR procedure favors detection and isolation of host genes affected at the transcriptional level by selecting for poly(A) tails but differs substantially from reverse transcription-PCR, Several unidentified macrophage gene fragments from genes that were either transcriptionally activated or downregulated following uptake of Listeria monocytogenes into J774 mouse macrophage cells were initially defined by this DPCR procedure, Because of the sensitivity of the DPCR technique, all of the genes exhibited less than a 10-fold difference in transcription compared with noninfected cells as measured by limiting-dilution PCR, One of the gene fragments has a very high level of homology with a mitogen-activated protein kinase phosphatase (MKP-1), whereas the other affected fragments showed no homologies to known gene sequences, In addition, one of the gene fragments (WS30-B2/1) was specifically downregulated after L. monocytogenes uptake and another gene was repressed by uptake of either Shigella flexneri or L. monocytogenes, while transcription of the genes represented by fragment WS13-B9/9, and to some extent MKP-1, was activated following general phagocytosis (i.e., following uptake of any species of bacterium tested). Further characterization of the affected genes was conducted by using mutants of L. monocytogenes. A hemolysin-negative mutant of L. monocytogenes failed to elicit transcriptional regulation of gene fragment WS10-B4/14 or WS30-B2/1, and it elicited only minimal regulation of MKP-1, suggesting that escape from the phagosome may be required to initiate these responses, Furthermore, mutants with mutations in mpl and actA, two genes whose gene products are involved in actin polymerization and intrahost spread, also did not induce regulation of WS10-B4/14. These results demonstrate that (i) DPCR can identify specific host cell genes which are differentially transcribed after infection with certain microorganisms and (ii) some of these genes may be new or may never before have been linked to interactions between hosts and pathogens. C1 UNIV WURZBURG,LEHRSTUHL MIKROBIOL,THEODOR BOVERI INST BIOWISSENSCH,D-97074 WURZBURG,GERMANY. RP Schwan, WR (reprint author), FDA,CBER,HFM440,LAB ENTER & SEXUALLY TRANSMITTED DIS,NIH CAMPUS,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. RI Schuller, Stephanie/C-1063-2013 OI Schuller, Stephanie/0000-0003-3260-9112 NR 43 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 1996 VL 64 IS 1 BP 91 EP 99 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TM718 UT WOS:A1996TM71800014 PM 8557379 ER PT J AU Dew, RB Susla, GM AF Dew, RB Susla, GM TI Once-daily aminoglycoside treatment SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Review ID CRITICALLY ILL; BETA-2-MICROGLOBULIN EXCRETION; ADAPTIVE RESISTANCE; GENTAMICIN THERAPY; DOSAGE REGIMENS; RENAL-FAILURE; BODY-WEIGHT; ANTIBIOTICS; NEPHROTOXICITY; TOBRAMYCIN C1 NIH,CLIN CTR PHARM DEPT,BETHESDA,MD 20892. RP Dew, RB (reprint author), ST ELIZABETHS MED CTR,DEPT PHARM SERV,736 CAMBRIDGE ST,BOSTON,MA 02135, USA. NR 58 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD JAN PY 1996 VL 5 IS 1 BP 12 EP 24 DI 10.1097/00019048-199601000-00004 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TT943 UT WOS:A1996TT94300005 ER PT B AU Thevenaz, P Unser, M AF Thevenaz, P Unser, M BE Delogne, P TI A pyramid approach to sub-pixel image fusion based on mutual information SO INTERNATIONAL CONFERENCE ON IMAGE PROCESSING, PROCEEDINGS - VOL I LA English DT Proceedings Paper CT International Conference on Image Processing (ICIP-96) CY SEP 16-19, 1996 CL LAUSANNE, SWITZERLAND SP IEEE Signal Proc Soc C1 NIH,BETHESDA,MD 20892. NR 0 TC 20 Z9 31 U1 0 U2 2 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-3259-8 PY 1996 BP 265 EP 268 PG 4 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BG63E UT WOS:A1996BG63E00067 ER PT B AU Unser, M AF Unser, M BE Delogne, P TI Vanishing moments and the approximation power of wavelet expansions SO INTERNATIONAL CONFERENCE ON IMAGE PROCESSING, PROCEEDINGS - VOL I LA English DT Proceedings Paper CT International Conference on Image Processing (ICIP-96) CY SEP 16-19, 1996 CL LAUSANNE, SWITZERLAND SP IEEE Signal Proc Soc C1 NCRR,IMAGE PROCESSING GRP,BIOMED ENGN & INSTRUMENTAT PROGRAM,NIH,BETHESDA,MD 20892. NR 0 TC 4 Z9 5 U1 0 U2 1 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-3259-8 PY 1996 BP 629 EP 632 PG 4 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BG63E UT WOS:A1996BG63E00158 ER PT J AU Tian, H Lempicki, R King, L Donoghue, E Samelson, LE Cohen, DI AF Tian, H Lempicki, R King, L Donoghue, E Samelson, LE Cohen, DI TI HIV envelope-directed signaling aberrancies and cell death of CD4(+) T cells in the absence of TCR co-stimulation SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytopathic effect; Fyn; HIV-1; Lck; protein tyrosine kinase ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-TYROSINE KINASE; RECEPTOR ZETA-CHAIN; ANTIGEN RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; MONOCLONAL-ANTIBODY; SYNCYTIUM FORMATION; SURFACE-ANTIGENS; ACTIVATION; PHOSPHORYLATION AB HIV-1 infection in CD4(+) T cells initiates a viral cytopathic effect (CPE) that is dependent on the activation of intracellular protein tyrosine kinases (PTK). PTK in T cells are also activated during the course of TCR or CD4 receptor engagement and the manner of receptor engagement may generate signals leading either to cell proliferation, tolerance induction (anergy) or programmed cell death (PCD), We have identified PTK triggered during the interaction of cells stably expressing surface HIV envelope (gp120/gp41; HIVenv) and CD4(+) T cells, which leads to extensive and rapid individual cell death, We have found that this killing is accompanied by tyrosine phosphorylation and activation of the CD4-associated p56(ick) kinase, and by activation of a second member of the src family of PTK, p59(fyn) kinase, normally associated with T cell stimulation through the TCR, Interestingly, in contrast with normal T cell signaling, the zeta subunit of the TCR fails to become tyrosine-phosphorylated during signaling accompanying HIV-directed cell killing, Downstream activation of the ZAP-70 PTK also does not occur, Unlike T cell apoptosis triggered by soluble HIVenv glycoproteins, which requires co-stimulation of CD4 and the antigen-specific TCR, T cell killing by membrane-associated HIVenv does not require TCR co-stimulation, because aberrant signaling and cell death are triggered by CD4(+) but TCR(-) cell lines, These results are the first report where dual activation of the Lck and Fyn PTK does not result in normal downstream signaling through the ZAP PTK, We suggest by analogy to SCID resulting from ZAP-70 mutations, that the dissociation of upstream PTK activation from ZAP-70 signaling contributes to T cell depletion by HIV and to the development of AIDS. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 60 TC 23 Z9 23 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 1996 VL 8 IS 1 BP 65 EP 74 DI 10.1093/intimm/8.1.65 PG 10 WC Immunology SC Immunology GA TT329 UT WOS:A1996TT32900007 PM 8671590 ER PT J AU Barthlott, T Potocnik, AJ Kohler, H Carsetti, R Pircher, H Fowlkes, BJ Eichmann, K AF Barthlott, T Potocnik, AJ Kohler, H Carsetti, R Pircher, H Fowlkes, BJ Eichmann, K TI A novel mouse thymocyte antigen (F3Ag): Down-regulation during the CD4(+)CD8(+) double-positive stage indicates positive selection SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD4; CD8; T cell development; TCR; thymic selection; transgenic mice ID T-CELL-RECEPTOR; INFECTED INSECT CELLS; TRANSGENIC MICE; MONOCLONAL-ANTIBODY; CD4+8+ THYMOCYTES; THYMIC SELECTION; PEANUT AGGLUTININ; CD8+ THYMOCYTES; EXPRESSION; SUBSETS AB We describe a novel mAb (F3) which reacts with a 65 kDa thymocyte surface protein, expressed on similar to 80% of thymocytes, referred to as F3Ag. In ontogeny, F3Ag expression begins in the CD4(-)CD8(-) double-negative (LN) CD25(+) population and is maintained through similar to 85% of the CD4(+)CD8(+) double-positive (DP) stage. DP cells with high TCR expression and CD4(+) single-positive (SP) cells are predominantly negative for F3Ag, whereas many CD8(+) SP thymocytes express F3Ag, F3Ag(-) it thymocytes show a reduced expression of RAG-1 and RAG-2, compared with F3Ag(+) DP cells. The shutdown of F3Ag expression during the DP stage is related to positive selection: mice deficient for MHs class I and class II molecules maintain F3Ag expression in almost all LP cells. Transgenic (tg) mice carrying TsR restricted for MHs class II show a more pronounced down-regulation of F3Ag in the DP compartment than normal mice, depending on the presence of a positively selecting MHC, The size of the F3Ag(-) DP subset is positively correlated with the efficacy of positive selection into the CD4(+) st compartment. Because some CD8(+) SP cells express F3Ag, the relationship between F3Ag down-regulation and positive selection is less obvious in DP cells of mice carrying MHC class I-restricted tg TCR, However, in reaggregate thymic organ cultures, sorted F3Ag(-) it cells differentiate into CD8(+) SP cells more rapidly than do F3Ag(+) it cells, Thus, after down-regulation in the it stage, a proportion of CD8(+) SP cells appears to re-express F3Ag. In addition, the proportion of FBAg- CD8(+) st cells depends on the efficacy of positive selection into the CD8 lineage, Taken together, the regulation of the expression of the F3Ag appears to be associated with signals that control thymic repertoire selection. C1 MAX PLANCK INST IMMUNBIOL,D-79108 FREIBURG,GERMANY. UNIV FREIBURG,INST MED MIKROBIOL,D-79104 FREIBURG,GERMANY. NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. RI carsetti, rita/K-7616-2016 OI carsetti, rita/0000-0002-2632-1078 NR 61 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 1996 VL 8 IS 1 BP 101 EP 113 DI 10.1093/intimm/8.1.101 PG 13 WC Immunology SC Immunology GA TT329 UT WOS:A1996TT32900011 PM 8671594 ER PT J AU Harkins, SW Taylor, JR Mattay, VS AF Harkins, SW Taylor, JR Mattay, VS TI Tacrine in patients with dementia of the Alzheimer's type: Cerebral perfusion change is related to change in mental status - Response SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE dementia of the Alzheimer's type; cerebral hypoperfusion; tacrine ID ORAL TETRAHYDROAMINOACRIDINE; SENILE DEMENTIA; DOUBLE-BLIND; BLOOD-FLOW; DISEASE; MULTICENTER; LECITHIN; TOMOGRAPHY; POPULATION; TRIAL AB We evaluated change in cerebral hypoperfusion by single photon emission computed tomography (SPECT) in 12 patients with a clinical diagnosis of dementia Alzheimer's type (DAT) before and after treatment with Tacrine. Based on clinical evaluation of the SPECT scans before and after treatment, two groups of patients were identified. One (N = 5) experienced a relative decrease in cerebral perfusion and a decrease in mini-mental status examination (MMSE) scores across the treatment interval and was labled ''non-responders.'' A second group consisting of 7 patients was judged as showing an increase in cerebral perfusion at follow-up compared to baseline and an increase in MMSE scores. These were termed ''responders''. The group difference in MMSE score change was significant (Fisher's exact test: p < 0.008). Sensitivity (0.85) and specificity (1.0) and Receiver Operating Characteristic values (discriminability or d' = 3.12 and bias or beta = 4.6) indicated that direction of change in cerebral perfusion was a reasonable indicator of direction of change in MMSE scores. These results suggest that SPECT determined changes in cerebral perfusion may be useful in identification of DAT patients who are more likely to respond to centrally active agents such as tacrine. C1 VIRGINIA COMMONWEALTH UNIV,DEMENTIA CLIN NEUROL,RICHMOND,VA 23298. NIMH,NIH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. RP Harkins, SW (reprint author), VIRGINIA COMMONWEALTH UNIV,DEPT GERONTOL,DEMENTIA CLIN,BOX 980266,RICHMOND,VA 23298, USA. NR 22 TC 5 Z9 5 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0020-7454 J9 INT J NEUROSCI JI Int. J. Neurosci. PY 1996 VL 84 IS 1-4 BP 149 EP 156 DI 10.3109/00207459608987260 PG 8 WC Neurosciences SC Neurosciences & Neurology GA UB227 UT WOS:A1996UB22700015 PM 8707476 ER PT J AU Bild, DE Sholinsky, P Smith, DE Lewis, CE Hardin, JM Burke, GL AF Bild, DE Sholinsky, P Smith, DE Lewis, CE Hardin, JM Burke, GL TI Correlates and predictors of weight loss in young adults: The CARDIA study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE weight loss; epidemiology; health behaviour; diet; exercise; obesity ID UNITED-STATES ADULTS; BODY-WEIGHT; SMOKING CESSATION; NATIONAL COHORT; BLOOD-PRESSURE; MAINTENANCE; OBESITY; GAIN; EXERCISE; RELAPSE AB OBJECTIVE: To determine associations of sociodemographic characteristics, behaviors, attitudes and medical factors with weight loss in a population-based biracial cohort of young adults. DESIGN:Two-year longitudinal observation study. SUBJECTS: 4278 black and white men and women aged 18-30 years in 1985-1986. MEASUREMENTS: Weight, height. education, income, subscapular skinfold thickness, waist and hip circumferences, medical history, smoking, physical activity, dietary energy, fat and alcohol intake, physical fitness measured by treadmill testing. self-reported dieting, history of weight loss and regain, perception of body size and belief in health consequences of overweight. RESULTS: Weight loss, defined as reduction of 5% or more of baseline weight, occurred in 8.9% of the cohort, ranging from 4.9% among white men who were not overweight at baseline to 21.5% among white women who were overweight. Weight loss was more common in women than men and in overweight white women than overweight black women, Although findings differed among the four race-sex groups, weight loss was generally associated with greater baseline fatness, lower baseline physical fitness level, self-perception of being overweight. dieting and previous weight loss and regain, Greater baseline fatness, a perception of being overweight and dieting were also associated with weight gain. Among the overweight, low baseline fitness and an increase in physical activity were the factors most consistently associated with weight loss. CONCLUSION: Weight loss in young adults varies by race, sex and body weight and is associated with a variety of behaviors and attitudes, some of which are also associated with weight gain and, thus, may be associated with weight fluctuation. C1 UNIV ALABAMA,DIV GEN & PREVENT MED,BIRMINGHAM,AL 35205. UNIV ALABAMA,SCH PUBL HLTH,DEPT BIOSTAT,BIRMINGHAM,AL 35294. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27157. RP Bild, DE (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,FED BLDG,ROOM 300,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [N01-HC-95095, N01-HC-48047] NR 38 TC 38 Z9 39 U1 1 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JAN PY 1996 VL 20 IS 1 BP 47 EP 55 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA TN489 UT WOS:A1996TN48900008 PM 8788322 ER PT J AU Gross, C Skowronski, RJ Plymate, SR Rhim, JS Peehl, DM Feldman, D AF Gross, C Skowronski, RJ Plymate, SR Rhim, JS Peehl, DM Feldman, D TI Simian virus 40-, but not human papillomavirus-, transformation of prostatic epithelial cells results in loss of growth-inhibition by 1,25-dihydroxyvitamin D-3 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE simian virus 40; human papillomavirus; prostate; 1,25-dihydroxyvitamin D-3 ID VITAMIN-D RECEPTOR; D ENDOCRINE SYSTEM; GENE-EXPRESSION; P53 GENE; CARCINOMA; CLONING; DIFFERENTIATION; ACTIVATION; SEQUENCE; BINDING AB In addition to its well known calcemic actions, 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D] exhibits differentiating and antiproliferative effects in several types of cancer cells. 1,25(OH)(2)D receptors (VDR) as well as 1,25(OH)(2)D-mediated growth-inhibition have been demonstrated in human prostate cancer cell lines. In order to further develop model systems for the study of 1,25(OH)(2)D action and to elucidate the mechanism of growth-inhibition, we studied several human prostate cell lines immortalized with either simian virus 40 (SV40) or human papillomavirus type 18 (HPV). The SV40-transformed cell lines P69SV40-T and P153SV40-T were not growth-inhibited by 1,25(OH)(2)D at concentrations as high as 100 nM, whereas the HPV-transformed cells PZ-HPV-7 and CA-HPV-10 were growth-inhibited. All cell lines expressed VDR, and VDR mRNA was demonstrated by Northern blot analysis. All cells exhibited induction of 24-hydroxylase mRNA, a 1,25(OH)(2)D responsive gene, after 1,25(OH)(2)D treatment. In an attempt to understand the apparent dissociation of 1,25(OH)(2)D actions in the SV40-transformed cells, we turned to the human prostate cancer cell line DU 145. These cells, like the SV40-transformed cells, are not growth-inhibited but demonstrate induction of 24-hydroxylase mRNA after 1,25(OH)(2)D treatment. DU 145 cells contain a mutated retinoblastoma gene (Rb) which contributes to their uncontrolled growth, analogous to the disruption of Rb by SV40 and HPV. We compared DU,145 cells to DU 145 cells transfected with normal Rb (DU 145/Rb). Similar to DU 145, DU 145/Rb cells were not growth-inhibited by 1,25(OH)(2)D, while 24-hydroxylase mRNA was induced. These results suggest that divergent pathways mediate the growth-inhibitory effect of 1,25(OH)(2)D and its induction of 24-hydroxylase. It also appears that the antiproliferative effect of 1,25(OH)(2)D is mediated by an Rb-independent mechanism. C1 STANFORD UNIV,SCH MED,DEPT MED,STANFORD,CA 94305. STANFORD UNIV,SCH MED,DEPT UROL,STANFORD,CA 94305. AMERICAN LAKE VET ADM MED CTR,TACOMA,WA 98493. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. NR 40 TC 13 Z9 13 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD JAN PY 1996 VL 8 IS 1 BP 41 EP 47 PG 7 WC Oncology SC Oncology GA TM024 UT WOS:A1996TM02400006 PM 21544329 ER PT J AU Magruder, KM Schulberg, HC Oxman, TE AF Magruder, KM Schulberg, HC Oxman, TE TI Measurement and meaning of disablement in primary care SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Editorial Material ID PSYCHIATRIC-DISORDERS; DIAGNOSTIC INTERVIEW; DEPRESSION; PREVALENCE; DISABILITY; ANXIETY; MANAGEMENT; SCHEDULE; OUTCOMES C1 UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15260. DARTMOUTH COLL SCH MED,LEBANON,NH. RP Magruder, KM (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 31 TC 4 Z9 4 U1 2 U2 2 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 1996 VL 26 IS 4 BP 355 EP 362 PG 8 WC Psychiatry SC Psychiatry GA WN760 UT WOS:A1996WN76000001 PM 9071630 ER PT J AU Alkon, DL AF Alkon, DL TI Persistent synaptic transformations store associative memory SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 3114 EP 3114 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85702048 ER PT J AU Neville, H Bavelier, D Corina, D Padmanabhan, S Clar, VP Braun, A Rauschecker, J Jezzard, P Turner, R AF Neville, H Bavelier, D Corina, D Padmanabhan, S Clar, VP Braun, A Rauschecker, J Jezzard, P Turner, R TI Effects of experience on cerebral organization for language: fMRI studies of hearing and deaf subjects SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 UNIV OREGON,EUGENE,OR 97403. UNIV WASHINGTON,SEATTLE,WA 98195. NIMH,BETHESDA,MD 20892. NIDCD,BETHESDA,MD. NHLBI,BETHESDA,MD 20892. INST NEUROL,LONDON WC1N 3BG,ENGLAND. RI Turner, Robert/C-1820-2008; Rauschecker, Josef/A-4120-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 4344 EP 4344 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85703289 ER PT J AU ZahnWaxler, C AF ZahnWaxler, C TI Social-emotional development SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 4551 EP 4551 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85703584 ER PT J AU Nsamenang, AB Lamb, ME AF Nsamenang, AB Lamb, ME TI Ecology of infants: Some implications from preliminary data regarding the Nso in northwest Cameroon SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 ECOLE NORMALE SUPER,BAMENDU,CAMEROON. NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 4651 EP 4651 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85703599 ER PT J AU Costa, PT AF Costa, PT TI Personality theories in the wake of the five-factor model SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 1 U2 6 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 4851 EP 4851 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85703908 ER PT J AU Colby, CL AF Colby, CL TI A neurophysiological distinction between attention and intention SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 2 U2 2 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 5641 EP 5641 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85704212 ER PT J AU Ungerleider, LG AF Ungerleider, LG TI Functional MRI studies of preattentive and attentive mechanisms in vision SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 5646 EP 5646 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85704217 ER PT J AU Tallent, KA Ramsey, NF Frank, JA Moonen, CT Weinberger, DR AF Tallent, KA Ramsey, NF Frank, JA Moonen, CT Weinberger, DR TI Test-retest reliability of functional MRI SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BETHESDA,MD 20892. RI Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 12451 EP 12451 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85700199 ER PT J AU Goulet, S Murray, EA AF Goulet, S Murray, EA TI Neural substrate of intramodal and crossmodal memory in rhesus monkeys SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NIMH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 38420 EP 38420 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85702777 ER PT J AU Dore, FY Thornton, J White, NM Murray, EA AF Dore, FY Thornton, J White, NM Murray, EA TI Effects of hippocampectomy on learning and retention of a touchscreen visuospatial task in rhesus monkeys SO INTERNATIONAL JOURNAL OF PSYCHOLOGY LA English DT Meeting Abstract C1 NIMH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0020-7594 J9 INT J PSYCHOL JI Int. J. Psychol. PY 1996 VL 31 IS 3-4 BP 38422 EP 38422 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VE857 UT WOS:A1996VE85702779 ER PT J AU Kondo, T Riesz, P AF Kondo, T Riesz, P TI Sonolysis of ubiquinone in aqueous solutions. An EPR spin-trapping study SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID FREE-RADICALS; LIPID-PEROXIDATION; PYROLYSIS RADICALS; ULTRASOUND; SONOCHEMISTRY; INHIBITION; VESICLES AB Free radical formation in aqueous solutions of ubiquinone (coenzyme Q(0)) induced by ultrasound was studied by EPR and spin trapping with 3,5-dibromo-4-nitrosobenzene sulphonate. When aqueous solutions of ubiquinone were sonicated with 50-kHz ultrasound in the presence of argon or nitrogen, radicals formed by addition of (OH)-O-. or H-. to the double bonds of the ubiquinone ring and methyl radicals were observed as the major spin adducts. The methyl radicals were formed by pyrolysis of ubiquinone. These radicals led to the degradation of ubiquinone. The reduced from of ubiquinone, ubiquinol, was formed by sonication in the presence of argon, and its formation was prevented by addition of native but not of denatured superoxide dismutase. Sodium formate, which scavenges (OH)-O-. to form CO2-., enhanced ubiquinol formation but partially inhibited the degradation of the ubiquinone ring. No ubiquinol was formed in nitrogen- or oxygen-saturated solutions under our conditions. These results indicate that ubiquinol was formed by reduction of ubiquinone by O-2(-.), which was generated by the sonolysis of argon-saturated water. C1 NCI,NIH,RADIAT BIOL BRANCH,BETHESDA,MD 20892. KOBE UNIV,SCH MED,DEPT RADIAT BIOPHYS,CHUO KU,KOBE 650,JAPAN. NR 27 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD JAN PY 1996 VL 69 IS 1 BP 113 EP 121 DI 10.1080/095530096146246 PG 9 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA TX068 UT WOS:A1996TX06800012 PM 8601750 ER PT J AU Quinn, TC AF Quinn, TC TI Association of sexually transmitted diseases and infection with the human immunodeficiency virus: Biological cofactors and markers of behavioural interventions SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article; Proceedings Paper CT Conference on HIV Behavioural Interventions CY JUN 21-23, 1995 CL ROYAL SOC MED, LONDON, ENGLAND SP Royal Soc Med, London, England, NIH, Off AIDS Res, Bethesda, USA HO ROYAL SOC MED ID GENITAL ULCER DISEASE; HIV-INFECTION; RISK-FACTORS; UNITED-STATES; HOMOSEXUAL MEN; HETEROSEXUAL TRANSMISSION; AIDS; EPIDEMIOLOGY; NAIROBI; AFRICA C1 NIAID, BETHESDA, MD 20892 USA. NR 81 TC 50 Z9 51 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0956-4624 EI 1758-1052 J9 INT J STD AIDS JI Int. J. STD AIDS PY 1996 VL 7 SU 2 BP 17 EP 24 DI 10.1258/0956462961917735 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UU794 UT WOS:A1996UU79400004 PM 8799790 ER PT J AU Krause, RM AF Krause, RM TI Reflections on the first decade of the HIV/AIDS pandemic: Opportunities and priorities for international behavioural research and interventions SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Article; Proceedings Paper CT Conference on HIV Behavioural Interventions CY JUN 21-23, 1995 CL ROYAL SOC MED, LONDON, ENGLAND SP Royal Soc Med, London, England, NIH, Off AIDS Res, Bethesda, USA HO ROYAL SOC MED RP Krause, RM (reprint author), NIH,FOGARTY INT CTR,16 CTR DR,MSC 6705,BETHESDA,MD 20892, USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC MEDICINE SERVICES LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PY 1996 VL 7 SU 2 BP 47 EP 51 DI 10.1258/0956462961917780 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UU794 UT WOS:A1996UU79400009 PM 8799795 ER PT J AU Williamson, DL Tully, JG Rosen, L Rose, DL Whitcomb, RF AbalainColloc, ML Carle, P Bove, JM Smyth, H AF Williamson, DL Tully, JG Rosen, L Rose, DL Whitcomb, RF AbalainColloc, ML Carle, P Bove, JM Smyth, H TI Spiroplasma diminutum sp nov, from Culex annulus mosquitoes collected in Taiwan SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID CLASS MOLLICUTES; CLASSIFICATION; DEFORMATION; TAXONOMY AB Initially, strain CUAS-1(T) (T = type strain), which was isolated from a frozen triturate of Culex annulus mosquitoes collected in Taiwan, was thought to be a member of spiroplasma group MI, This placement was based on the spiroplasma deformation test titer observed when strain CUAS-1(T) spiroplasmas were tested with Spiroplasma monobiae MQ-1(T) antiserum, The results of subsequent reciprocal spiroplasma deformation, metabolism inhibition, and growth inhibition tests clearly revealed that strain CUAS-1(T) is not serologically related to previously described spiroplasma groups (groups I to XXIV) and thus is a representative of a new group, group XXV, Strain CUAS-1(T) was characterized by using the minimal standards for mollicute species descriptions, During logarithmic-phase growth, strain CUAS-1(T) cells are characteristically very short helices with 1.5 to 2 helical turns (1 to 2 mu m), highly motile, and bounded by a single trilaminar membrane and form granular colonies with satellites when the organism is grown aerobically on MID medium containing 1.6% agar, Growth in M1D broth occurs at temperatures ranging from 10 to 37 degrees C, and the optimum temperature is 30 degrees C, Substrate utilization tests revealed that cholesterol is required for growth, that glucose is hydrolyzed, and that arginine is not hydrolyzed both in the presence and in the absence of glucose, The genome of strain CUAS-1(T) is 1,080 kbp long, and the guanine-plus-cytosine content is 26 +/- 1 mol%, On the basis of the results of our studies we propose that strain CUAS-1(T) (group XXV) should be placed in a new species, Spiroplasma diminutum. Strain CUAS-1 (= ATCC 49235) is the type strain of S. diminutum. C1 NIAID,FREDERICK CANC RES FACIL,MOLEC MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD 21702. UNIV HAWAII MANOA,PACIFIC BIOMED RES CTR,HONOLULU,HI 96822. USDA,BELTSVILLE AGR RES CTR,INST PLANT PROTECT,INSECT PATHOL LAB,BELTSVILLE,MD 20705. FAC MED BREST,BACTERIOL LAB,F-29285 BREST,FRANCE. INRA,LAB BIOL CELLULAIRE & MOLEC,F-33883 VILLENAVE DORNON,FRANCE. UNIV BORDEAUX 2,F-33883 VILLENAVE DORNON,FRANCE. RP Williamson, DL (reprint author), SUNY STONY BROOK,HLTH SCI CTR,DEPT ANAT SCI,STONY BROOK,NY 11794, USA. NR 25 TC 18 Z9 18 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JAN PY 1996 VL 46 IS 1 BP 229 EP 233 PG 5 WC Microbiology SC Microbiology GA TP738 UT WOS:A1996TP73800033 PM 8573499 ER PT J AU Tobin, GJ Nagashima, K Gonda, MA AF Tobin, GJ Nagashima, K Gonda, MA TI Synthesis and assembly of chimeric human immunodeficiency virus gag pseudovirions SO INTERVIROLOGY LA English DT Article; Proceedings Paper CT Workshop on Chimeric Virus-Like Particles as Vaccines CY MAY 17-19, 1995 CL HUMBOLDT UNIV, CHARITE MED SCH, BERLIN, GERMANY HO HUMBOLDT UNIV, CHARITE MED SCH DE human immunodeficiency virus; pseudovirion; immunoelectron microscopy; baculovirus; virus-like particle; particulate vaccines ID RECOMBINANT BACULOVIRUS; TYPE-1 GAG; PARTICLE FORMATION; RECEPTOR-BINDING; HIV-1 INFECTION; INSECT CELLS; EXPRESSION; GENE; RESPONSES; PRECURSOR AB Expression of the HIV Gag precursor in insect cells by recombinant baculoviruses results in the assembly and budding of noninfectious pseudovirions that resemble immature virus. Three strategies for packaging additional viral epitopes into pseudovirions were examined: coinfection of insect cells with individual baculoviruses encoding separate Gag and Env structural genes, inframe Gag-Env fusion proteins, and Gag-frameshift-Env fusion proteins, Electron microscopy and Western blot analysis indicated that neither the coinfection nor the inframe fusion strategies reliably produced large quantities of structurally stable chimeric pseudovirions. The frameshift fusion method utilized the retroviral Gag-Pol ribosomal frameshift mechanism for the coexpression of Gag and Gag-frameshift-Env fusion proteins. Large quantities of pseudovirions containing both the Gag and Env epitopes were produced in insect cells, Mice inoculated with the Gag-frameshift-Env pseudovirions developed cytotoxic lymphocyte responses to both HIV Gag and Env epitopes, Vaccine and immunotherapeutic applications of chimeric pseudovirions are discussed. RP Tobin, GJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,LAB CELL & MOL STRUCT,SAIC,POB B,FREDERICK,MD 21702, USA. NR 43 TC 11 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD JAN-APR PY 1996 VL 39 IS 1-2 BP 40 EP 48 DI 10.1159/000150473 PG 9 WC Virology SC Virology GA VW123 UT WOS:A1996VW12300006 PM 8957668 ER PT S AU Corcoran, ML EmmertBuck, MR McClanahan, JL PelinaParker, M StetlerStevenson, WG AF Corcoran, ML EmmertBuck, MR McClanahan, JL PelinaParker, M StetlerStevenson, WG BE Suzuki, K Bond, JS TI TIMP-2 mediates cell surface binding of MMP-2 SO INTRACELLULAR PROTEIN CATABOLISM SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 10th International Conference on Intracellular Protein Catabolism CY OCT 30-NOV 03, 1994 CL TOKYO, JAPAN SP Commemorat Assoc Japan World Exposit 1970, Fdn Adv Int Sci, Pharm Soc Japan, Japanese Agr Chem Soc Japan, Japanese Biochem Soc, Japanese Soc Cell Biol, Molec Biol Soc Japan, Protein Engn Soc Japan ID ERYTHROID-POTENTIATING ACTIVITY; CONSERVED PEPTIDE SEQUENCE; HUMAN-TISSUE INHIBITOR; IV COLLAGENASE; PLASMINOGEN-ACTIVATOR; CYSTEINE-SWITCH; METALLOPROTEINASES-2 TIMP-2; TERMINAL DOMAIN; FAMILY; GELATINASE AB In order to understand the mechanism for neoplastic cell invasion, we utilized binding studies of TIMP-2, gelatinase A and the TIMP-2/gelatinase A complex to neoplastic cells and correlated these results with their capacity to invade a matrix substrate in a modified Boyden chamber assay. Binding studies were performed on malignant human breast cancer cells and fibrosarcoma cells with rTIMP-2, rGelatinase A, and TIMP-2/gelatinase A complex. Competition studies of the binding characteristics of these proteins indicated that gelatinase A and gelatinase A/TIMP-2 complex bound to the surface of cells via TIMP-2. Furthermore, the localization of either latent or active protease to the surface of MDA-MB-435 breast cancer cells facilitated the invasion of these neoplastic cells through a matrigel barrier. This suggests that in addition to binding this complex, these cells can activate this pro-enzyme-inhibitor complex and use this activity to facilitate cellular invasion. Moreover, their enhanced invasion was suppressed by exogenous additions of rTIMP-2. A working hypothesis and model for the role of gelatinase A/TIMP-2 complex in cellular invasion is presented. RP Corcoran, ML (reprint author), NCI,EXTRACELLULAR PATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 41 TC 14 Z9 14 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45201-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 389 BP 295 EP 304 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BF18P UT WOS:A1996BF18P00036 PM 8861023 ER PT B AU Basta, M AF Basta, M BE Kazatchkine, MD Morell, A TI Modulation of complement-mediated tissue damage by intravenous immunoglobulin SO INTRAVENOUS IMMUNOGLOBULIN: RESEARCH AND THERAPY LA English DT Proceedings Paper CT 4th Interlaken International Symposium on Intravenous Immunoglobulin Therapy CY JUN, 1996 CL INTERLAKEN, SWITZERLAND SP Swiss Red Cross, ZLB Cent Lab, Blood Transfus Serv, Bern, Sandoz Pharma Ltd, Basel RP Basta, M (reprint author), NIH,DEPT HLTH & HUMAN SERV,BLDG 10,10 CTR DR MSC 1382,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER, ENGLAND LA6 2LA BN 1-85070-766-9 PY 1996 BP 83 EP 87 PG 5 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA BH05D UT WOS:A1996BH05D00011 ER PT B AU Dalakas, MC AF Dalakas, MC BE Kazatchkine, MD Morell, A TI Clinical relevance in modulation of complement-mediated tissue damage by intravenous immunoglobulin: Implications in dermatomyositis, Guillain-Barre syndrome and myasthenia gravis SO INTRAVENOUS IMMUNOGLOBULIN: RESEARCH AND THERAPY LA English DT Proceedings Paper CT 4th Interlaken International Symposium on Intravenous Immunoglobulin Therapy CY JUN, 1996 CL INTERLAKEN, SWITZERLAND SP Swiss Red Cross, ZLB Cent Lab, Blood Transfus Serv, Bern, Sandoz Pharma Ltd, Basel RP Dalakas, MC (reprint author), NIH,NEUROMUSCULAR DIS SECT,NINDS,BLDG 10,10 CTR DR MSC 1382,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER, ENGLAND LA6 2LA BN 1-85070-766-9 PY 1996 BP 89 EP 93 PG 5 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA BH05D UT WOS:A1996BH05D00012 ER PT B AU Dalakas, MC AF Dalakas, MC BE Kazatchkine, MD Morell, A TI Experience with intravenous immunoglobulin for the treatment of inflammatory myopathies SO INTRAVENOUS IMMUNOGLOBULIN: RESEARCH AND THERAPY LA English DT Proceedings Paper CT 4th Interlaken International Symposium on Intravenous Immunoglobulin Therapy CY JUN, 1996 CL INTERLAKEN, SWITZERLAND SP Swiss Red Cross, ZLB Cent Lab, Blood Transfus Serv, Bern, Sandoz Pharma Ltd, Basel RP Dalakas, MC (reprint author), NINCDS,NIH,NEUROMUSCULAR DIS SECT,BLDG 10,10 CTR DR,MSC 1382,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER, ENGLAND LA6 2LA BN 1-85070-766-9 PY 1996 BP 275 EP 284 PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA BH05D UT WOS:A1996BH05D00036 ER PT J AU Smith, M Ho, PTC AF Smith, M Ho, PTC TI Pediatric drug development: A perspective from the cancer therapy evaluation program (CTEP) of the National Cancer Institute (NCI) SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE bryostatin; cyclin-dependent kinases; differentiation agents; isoprenylation; pediatric; phase I; protein kinase C; trial design ID PROTEIN-KINASE-C; TRANS-RETINOIC ACID; PHASE-I TRIAL; CELL-CYCLE ARREST; SOLID TUMORS; CLINICAL-TRIALS; FARNESYLTRANSFERASE INHIBITORS; EXPERIMENTAL CHEMOTHERAPY; HUMAN MEDULLOBLASTOMA; PERILLYL ALCOHOL AB Well-designed and carefully conducted pediatric phase I trials are critical to the process of evaluating new agents for potential benefit in children with cancer, and the National Cancer Institute (NCI) has for a number of years sponsored pediatric phase I trials. The development of new agents for children with cancer differs in important ways from drug development for adults with cancer, primarily necessitated by the smaller number of children eligible for phase I trials in comparison to adults. Pediatric drug development is characterized by a greater need to prioritize new agents for evaluation, since many more agents can be evaluated in adults than can be evaluated in children. Pediatric phase I trials are also commonly conducted as multi-institutional collaborations, since most single institutions do not have enough eligible patients to complete phase I trials within a reasonable time. In addition, pediatric phase I trials begin at doses close to the adult maximum tolerated dose, thereby minimizing the number of patients required to complete pediatric phase I trials. While pediatric phase I trials have traditionally evaluated conventional cytotoxic agents, new classes of agents with distinctive mechanisms of action are entering clinical evaluation. These agents target specific cellular proteins (e.g., protein tyrosine kinases, protein kinase C isoforms, enzymes involved in controlling progression through the cell cycle). Determining whether these agents with specificity for critical cellular proteins will be effective anti-cancer agents will be an important objective of pediatric clinical investigations in the coming years. C1 NCI,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. RP Smith, M (reprint author), NCI,CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH,PEDIAT SECT,BETHESDA,MD 20892, USA. NR 73 TC 9 Z9 9 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PY 1996 VL 14 IS 1 BP 11 EP 22 DI 10.1007/BF00173678 PG 12 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA VG017 UT WOS:A1996VG01700002 PM 8880389 ER PT J AU Forsyth, P Cairncross, G Stewart, D Goodyear, M Wainman, N Eisenhauer, E AF Forsyth, P Cairncross, G Stewart, D Goodyear, M Wainman, N Eisenhauer, E TI Phase II trial of docetaxel in patients with recurrent malignant glioma: A study of the National Cancer Institute of Canada Clinical Trials group SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE docetaxel; malignant glioma; phase II ID BRAIN-TUMORS; CHEMOTHERAPY; PACLITAXEL AB Background. We conducted a phase II study to determine the response to, and toxicity of, docetaxel (Taxotere; Rhone Poulenc Rorer Pharmaceuticals, Inc) in patients with recurrent malignant glioma. Patients and methods. Eighteen patients with recurrent malignant glioma were treated with 100 mg/m(2) (no prior chemotherapy) or 75 mg/m(2) (prior adjuvant chemotherapy) of docetaxel intravenously over 1 hour, every 3 weeks. Premedication with dexamethasone, diphenhydramine and ranitidine or cimetidine was given to all patients. Five (28%) had gioblastoma multiforme (GEM) and the rest other malignant gliomas. Eleven (61%) had an ECOG performance status of 0 or 1, and 13 (72%) were on corticosteroids at the start of treatment. Rigorous response criteria were used. All were eligible and evaluable for response. Results. No complete or partial responses were observed; the objective response rate was 0% (95% confidence interval: 0-15.3%). Patients received a median of 2 cycles (range, 1-6). Grade 3 or 4 neutropenia occurred in 17 (94%) patients and was associated with fever that required intravenous antibiotics in 4 (22%) patients. An additional patient received intravenous antibiotics for an infection not associated with neutropenia. Six (33%) patients had mild hypersensitivity reactions. Onychodystrophy, peripheral edema and peripheral neuropathy were uncommon and mild. Conclusions. Docetaxel has no significant activity in patients with recurrent malignant glioma. C1 FOOTHILLS PROV GEN HOSP,TOM BAKER CANC CTR & CLIN NEUROSCI,DEPT MED,CALGARY,AB T2N 2T9,CANADA. UNIV WESTERN ONTARIO,DEPT CLIN NEUROL SCI & ONCOL,LONDON,ON,CANADA. UNIV OTTAWA,DEPT MED,OTTAWA,ON,CANADA. OTTAWA REG CANC CTR,OTTAWA,ON K1Y 4K7,CANADA. LONDON REG CANC CTR,LONDON,ON N6A 4L6,CANADA. HAMILTON REG CANC CTR,HAMILTON,ON L8V 1C3,CANADA. NCI,CANADA CLIN TRIALS GRP,KINGSTON,ON,CANADA. NR 8 TC 26 Z9 26 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PY 1996 VL 14 IS 2 BP 203 EP 206 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA VP123 UT WOS:A1996VP12300010 PM 8913841 ER PT J AU Wang, Y Burnier, M Detrick, B Hooks, JJ AF Wang, Y Burnier, M Detrick, B Hooks, JJ TI Genetic predisposition to coronavirus-induced retinal disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE coronavirus; genetic disease; retinal degeneration; retinal inflammation; viral infection AB Purpose. Retinal inflammatory and degenerative processes in humans and animals frequently are associated with genetic factors. The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. The genetic constitution of the host and the virus serotype can be critical factors in determining the outcome of a virus infection. The purpose of this study was to evaluate the possible role of host genetics in murine coronavirus-induced retinal disease. Methods. JHM virus was inoculated by the intravitreal route into BALB/c, CD-1, and A/J mice. At varying times after inoculation, eye tissues were evaluated histologically. Antibody responses to the virus were evaluated by neutralization assays. Results. JHM virus induces a biphasic retinal disease in BALB/c mice. In the early phase, 1 to 7 days after inoculation, retinal vasculitis is observed. The second phase, characterized by retinal degeneration in the absence of inflammation, is seen by day 10 and progresses for several months. There is a similar biphasic disease process in JHM virus-infected A/J mice. However, retinal changes are less severe than those seen in BALB/c mice. Retinal tissue damage induced by JHM virus in CD-1 mice is different. Only the early phase of the disease, consisting of retinal vasculitis, was observed. These CD-1 mice do not develop the retinal degenerative disease. In fact, after day 10, the retina has a normal appearance. These differences in retinal tissue damage are seen over a wide range of infectivity of the virus inocula. Virus concentrations ranging from 10(1.4) to 10(4.4) TCID50/5 mu l were capable of inducing both inflammation and degeneration in BALB/c mice, whereas, the highest concentration of virus (10(4.4) TCID50/5 mu l) in CD-1 mice resulted in only the early inflammatory changes. Conclusions. The authors show that the genetics of the host can profoundly affect the nature of retinal tissue damage. These studies substantiate the concept that a virus can indeed trigger retinal degenerative processes in genetically susceptible hosts. C1 NEI,IMMUNOL & VIROL SECT,IMMUNOL LAB,BETHESDA,MD 20892. MCGILL UNIV,DEPT OPHTHALMOL,MONTREAL,PQ H3A 2T5,CANADA. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. NR 9 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 1996 VL 37 IS 1 BP 250 EP 254 PG 5 WC Ophthalmology SC Ophthalmology GA TQ213 UT WOS:A1996TQ21300028 PM 8550331 ER PT B AU Bouville, A AF Bouville, A GP AUSTRIAN ASSOC RADIAT PROTECT TI Evaluation of thyroid doses from radioiodine releases SO IRPA9 - 1996 INTERNATIONAL CONGRESS ON RADIATION PROTECTION / NINTH INTERNATIONAL CONGRESS OF THE INTERNATIONAL RADIATION PROTECTION ASSOCIATION, PROCEEDINGS, VOL 1 LA English DT Proceedings Paper CT 1996 International Congress on Radiation Protection / 9th International Congress of the International-Radiation-Protection-Association (IRPA9) CY APR 14-19, 1996 CL VIENNA, AUSTRIA SP Austrian Assoc Radiat Protect, Int Radiat Protect Assoc RP Bouville, A (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT RADIATION PROTECTION ASSOC PI MONTREAL PA 2155 RUE GUY, BUREAU 820, MONTREAL PQ H3H 2R9, CANADA BN 3-9500255-4-5 PY 1996 BP A197 EP A204 PG 8 WC Engineering, Environmental; Public, Environmental & Occupational Health; Nuclear Science & Technology SC Engineering; Public, Environmental & Occupational Health; Nuclear Science & Technology GA BH13P UT WOS:A1996BH13P00021 ER PT J AU Mozes, E Segal, R Sthoeger, Z Dayan, M Zinger, H Kohn, LD Singer, DS AF Mozes, E Segal, R Sthoeger, Z Dayan, M Zinger, H Kohn, LD Singer, DS TI Modulation of experimental systemic lupus erythematosus SO ISRAEL JOURNAL OF MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT 9th Autoimmunity Meeting CY JAN 03, 1995 CL CHAIM SHEBA MED CTR, TEL HASHOMER, ISRAEL HO CHAIM SHEBA MED CTR DE autoimmunity; systemic lupus erythematosus; modulation of disease; cytokine profile; class I role in SLE ID ANTI-DNA IDIOTYPE; INDUCTION; MICE C1 NIDDK, BIOCHEM & METAB LAB, BETHESDA, MD USA. NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. RP Mozes, E (reprint author), WEIZMANN INST SCI, DEPT CHEM IMMUNOL, IL-76100 REHOVOT, ISRAEL. NR 16 TC 1 Z9 1 U1 0 U2 0 PU ISRAEL JOURNAL MED SCIENCES PI JERUSALEM PA 2 ETZEL ST, FRENCH HILL, JERUSALEM 97853, ISRAEL SN 0021-2180 J9 ISRAEL J MED SCI JI Isr. J. Med. Sci. PD JAN PY 1996 VL 32 IS 1 BP 19 EP 21 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA TT001 UT WOS:A1996TT00100005 PM 8550341 ER PT J AU Wolf, SS Weinberger, DR AF Wolf, SS Weinberger, DR TI Schizophrenia: A new frontier in developmental neurobiology SO ISRAEL JOURNAL OF MEDICAL SCIENCES LA English DT Article DE schizophrenia; development; clozapine ID C-FOS; CORTICAL DEVELOPMENT; TEMPORAL-LOBE; RAT STRIATUM; EXPRESSION; ABNORMALITIES; CLOZAPINE; DISTURBANCES; AMPHETAMINE; HALOPERIDOL AB Evidence from diverse sources, including postmortem investigations, in vivo imaging studies and animal models, suggests that schizophrenia has its origins in early cortical maldevelopment which in rum may lead to dysfunctional connectivity during brain maturation and clinical symptomatology in early adulthood. Antipsychotic drugs, including the atypical agent clozapine, appear to act at key sites involved in higher cortical-limbic connectivity, possibly mediated by a variety of neurotransmitters. Studies of gene expression may provide a better understanding of how antipsychotic drug effects are integrated at the postsynaptic level. The data from schizophrenia research are discussed within a neurodevelopmental framework. RP Wolf, SS (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,DIV INTRAMURAL RES PROGRAMS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 40 TC 3 Z9 3 U1 0 U2 0 PU ISRAEL JOURNAL MED SCIENCES PI JERUSALEM PA 2 ETZEL ST, FRENCH HILL, JERUSALEM 97853, ISRAEL SN 0021-2180 J9 ISRAEL J MED SCI JI Isr. J. Med. Sci. PD JAN PY 1996 VL 32 IS 1 BP 51 EP 55 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TT001 UT WOS:A1996TT00100012 PM 8550349 ER PT J AU Tsai, CM Perng, RP Chang, KT Venzon, D Gazdar, AF AF Tsai, CM Perng, RP Chang, KT Venzon, D Gazdar, AF TI Evaluation of the relative cytotoxic effects of anticancer agents in serum-supplemented versus serum-free media using a tetrazolium colorimetric assay SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE serum-free medium; drug testing; anticancer agent; lung cancer ID CANCER CELL-LINES; HUMAN-LUNG-CANCER; FREE DEFINED MEDIUM; CLINICAL SPECIMENS; GROWTH; INVITRO; CARCINOMA; 5-FLUOROURACIL; ESTABLISHMENT; METHOTREXATE AB Most cell culture and in vitro drug sensitivity assays utilize serum-supplemented media (SSM). However, fully defined serum-free media (SFM) offer several advantages and are being used increasingly for initiation and maintenance of cell cultures. Because serum inhibits the in vitro cytotoxicity of certain antineoplastic agents, we investigated the inter-relationships between medium type, cell proliferation and cytotoxic effect. Twenty-four human lung cancer cell lines were tested with nine anticancer agents in both media types, A semi-automated tetrazolium (MTT) colorimetric assay was used for assaying cell survival. Cell lines initiated and maintained in SFM preferentially proliferated in that medium type or proliferated equally well in both media types. In contrast, cell lines established in SSM varied considerably in their medium of preference. There appeared to be a direct correlation or trend between cell proliferative rate and cytotoxicity of all drugs with the possible exceptions of methotrexate and carmustine. In general, the cell lines were more sensitive to anticancer agents when they were exposed in the culture medium in which they preferentially proliferated. Therefore, to determine the influence of culture media on cytotoxicity, we analyzed the data only from lines that replicated equally efficiently in both media. After correction for cell proliferative rate, SSM had a negative effect on the cytotoxic action of some drugs (especially methotrexate, 5-fluorouracil and, to a lesser extent, mitomycin-C). Our results demonstrate that fully defined SFM may be suitable for initiating cell lines and for use in in vitro cytotoxicity assays for selection of individualized therapy or for screening of new anti-neoplastic agents, and thus may increase the number of antineoplastic agents that can be tested satisfactorily. C1 NATL YANG MING UNIV,SCH MED,DEPT MED,TAIPEI 11217,TAIWAN. NCI,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX. RP Tsai, CM (reprint author), VET GEN HOSP,DEPT CHEST,SECT THORAC ONCOL,TAIPEI 11217,TAIWAN. RI Venzon, David/B-3078-2008 NR 33 TC 5 Z9 7 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD JAN PY 1996 VL 87 IS 1 BP 91 EP 97 PG 7 WC Oncology SC Oncology GA TZ320 UT WOS:A1996TZ32000015 PM 8609055 ER PT J AU Premkumar, A Marincola, F Taubenberger, J Chow, C Venzon, D Schwartzentruber, D AF Premkumar, A Marincola, F Taubenberger, J Chow, C Venzon, D Schwartzentruber, D TI Metastatic melanoma: Correlation of MRI characteristics and histopathology SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance; melanoma; pathology ID UVEAL MALIGNANT MELANOMAS; CHOROIDAL MELANOMA; RELAXATION RATES; RESONANCE; TUMORS; IMAGE AB To correlate the findings on MRI with histopathology of metastatic melanoma, MRI was performed on 29 patients with 36 lesions, using spin-echo and inversion recovery sequences. Histopathologic examination of lesions was performed within 4 weeks of imaging. Lesions were categorized according to cell type and were also evaluated for the presence and extent of melanin, iron, and necrosis, These data were then correlated with the signal intensities of the lesions. Enhancement of lesions after injection of intravenous gadolinium was calculated and correlated to vascularity of the tumor. Melanin was present more frequently in lesions appearing hyperintense or with mixed signal intensity (12/15) than in those appearing hypo- or isointense (6/21) on the T1-weighted sequence. This trend was significant (P=.013), Also, more lesions appearing mixed, ie, having both hypo- and hyperintense components, contained melanin (15/23), as opposed to lesions that appeared to be only hyperintense (3/13) on the STIR sequence, There was no clear association between signal intensity and melanin content on the T2-weighted sequence. There was no significant association between the signal intensities on the MR images and the iron content, tumor size, or tumor cell type of these lesions, There was no clear association between enhancement after gadolinium injection and vascularity, as assessed by histology. The authors concluded in this study that T1 shortening and hypointensity on the STIR sequence seen in patients with metastatic melanoma are most closely related to the melanin content of the tumor. RP Premkumar, A (reprint author), NIH,HENRY M JACKSON FDN,CTR CLIN,DEPT DIAGNOST RADIOL,BLDG 10,ROOM 1C660,10 CTR DR,MSC 1182,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 17 TC 32 Z9 32 U1 0 U2 2 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD JAN-FEB PY 1996 VL 6 IS 1 BP 190 EP 194 DI 10.1002/jmri.1880060134 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TZ568 UT WOS:A1996TZ56800033 PM 8851427 ER PT J AU Cereseto, A Mulloy, JC Franchini, G AF Cereseto, A Mulloy, JC Franchini, G TI Insights on the pathogenicity of human T-lymphotropic/leukemia virus types I and II SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article; Proceedings Paper CT VIIth International Conference on Human Retrovirology CY OCT 17-21, 1995 CL INST PASTEUR, PARIS, FRANCE HO INST PASTEUR DE human T-lymphotropic/leukemia virus type I (HTLV-I); HTLV-II; T-cell transformation ID RECEPTOR-GAMMA-CHAIN; CELL LEUKEMIA-LYMPHOMA; PAPILLOMAVIRUS-E5 TRANSFORMING PROTEIN; GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR GENE; HTLV-1 TAX PROTEIN; JAK-3 JANUS KINASE; INTERLEUKIN-2 RECEPTOR; IL-2 RECEPTOR; BETA-CHAIN AB Human T-lymphotropic/leukemia virus types I and II (HTLV-I and HTLV-II) are phylogenetically and immunologically related viruses that differ in their pathogenicity in vivo. HTLV-I is the etiologic agent of adult T-cell leukemia/lymphoma, as well as a chronic progressive myelopathy, HTLV-I-associated myelopathy/tropical spastic paraparesis. In contrast, HTLV-II has not been conclusively associated with specific diseases. Both HTLV-I and HTLV-II transform CD4(+) T-cells in vitro, but their in vivo target cells appear to differ. HTLV-I is found mainly in CD4(+) cells, whereas HTLV-II has been demonstrated mainly in CD8(+) cells. Clearly the definition of the viral genetic determinants responsible for the different tropism and pathogenicity in vivo may provide the basis of our understanding of the HTLV-I oncogenicity. In this short review we emphasize two aspects of viral infection of T cells: (1) the influence of viral infection on the major proteins involved in the G0-G1 phase of the cell cycle and (2) the effect of viral infection on the S phase of the cell cycle, i.e., the interleukin-2 receptor pathway. C1 NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 80 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PY 1996 VL 13 SU 1 BP S69 EP S75 DI 10.1097/00042560-199600001-00013 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VG828 UT WOS:A1996VG82800013 PM 8797707 ER PT J AU Jacobson, S AF Jacobson, S TI Cellular immune responses to HTLV-I: Immunopathogenic role in HTLV-I-associated neurologic disease SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article; Proceedings Paper CT VIIth International Conference on Human Retrovirology CY OCT 17-21, 1995 CL INST PASTEUR, PARIS, FRANCE HO INST PASTEUR DE HTLV-I-immunopathogenesis; disease association; cytotoxic T lymphocyte ID TROPICAL SPASTIC PARAPARESIS; VIRUS TYPE-I; CYTOTOXIC LYMPHOCYTES-T; CENTRAL-NERVOUS-SYSTEM; PROVIRAL DNA; SPINAL-CORD; HAM TSP; MYELOPATHY; LEUKEMIA; PX AB This review examines current information on cellular immune responses to the human T lymphotropic virus type I (HTLV-I). HTLV-I has been associated with a number of diseases, but this review focuses primarily on the relationship of HTLV-I with a slowly progressive neurologic disorder termed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In particular, this review discusses the role of cellular immune responses to HTLV-I in patients with HAM/TSP and how these responses may be associated with the pathogenesis of this disorder, While a number of immunologic responses have been shown to be abnormal in HAM/TSP patients, studies on HTLV-I-specific cytotoxic T-cell responses (cytotoxic T lymphocytes) are specifically examined. By defining such antigen-specific functional cellular host responses to HTLV-I, ae hope to understand better the underlying mechanisms that may be involved in the neuropathology of HTLV-I-associated neurologic disease. This has led to a number of HTLV-I-associated immunopathogenic models that may be operative in HAM/TSP patients. Importantly, based on these models, potential immunotherapeutic strategies for disease intervention can be devised. Moreover, such an analysis may have significant implications for our understanding of other HTLV-I-associated clinical disorders. RP Jacobson, S (reprint author), NINCDS,VIRAL IMMUNOL SECT,NEUROIMMUNOL BRANCH,NIH,BLDG 10,ROOM 5B-16,BETHESDA,MD 20892, USA. NR 46 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PY 1996 VL 13 SU 1 BP S100 EP S106 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VG828 UT WOS:A1996VG82800017 PM 8797711 ER PT J AU Waldmann, TA AF Waldmann, TA TI The promiscuous IL-2/IL-15 receptor: A target for immunotherapy of HTLV-I-associated disorders SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article; Proceedings Paper CT VIIth International Conference on Human Retrovirology CY OCT 17-21, 1995 CL INST PASTEUR, PARIS, FRANCE HO INST PASTEUR DE human T-cell lymphotropic virus I (HTLV-I); interleukin-2 (IL-2); IL-2/IL-15 receptor; adult T-cell leukemia; HTLV-1-associated disorders ID T-CELL LEUKEMIA; ACTIVATED KILLER-CELLS; ANTI-TAC-H; INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODY; HUMANIZED ANTIBODY; GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; IL-2 RECEPTOR; RADIOIMMUNOTHERAPY AB Human T-cell lymphotrophic virus I (HTLV-I)-encoded tax plays a role in the early phases of HTLV-I-induced disease by deregulating the expression of the genes that encode interleukin-2 (IL-2) and the multisubunit (IL-2R alpha, IL-2R beta, and IL-2R gamma) IL-2 receptor (IL-2). However, later in the course of the disease adult T-cell leukemia (ATL), cells no longer produce IL-2 yet continue to express the IL-2R. During studies to define the pathogenic mechanisms that underlie this IL-2-independent proliferation, we defined a cytokine designated IL-T/IL-15 that stimulates T-cell proliferation and requires the expression of IL-2R beta and IL-2R gamma for its action. To exploit the fact that IL-2Rs are present on abnormal T cells in patients with tropical parasitic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and ATL but not on normal resting cells, different forms of IL-2R-directed therapy have been initiated. Unmodified humanized anti-Tac is being used to treat patients with TSP/HAM. To enhance its effector function for the treatment of ATL anti-Tac was armed with alpha- and beta-emitting radionuclides. In a clinical trial with Y-90-anti-Tac at the doses used (5, 10, and 15 mCi), 9 of the 18 patients with ATL underwent a partial or sustained complete remission. Thus the clinical application of IL-2R-directed therapy using a humanized monoclonal antibody or that antibody armed with radionuclides provides a new perspective for the treatment of autoimmune disorders such as TSP/HAM and certain neoplastic diseases including ATL. RP Waldmann, TA (reprint author), NEI,METAB BRANCH,NIH,BETHESDA,MD 20892, USA. NR 43 TC 11 Z9 11 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PY 1996 VL 13 SU 1 BP S179 EP S185 DI 10.1097/00042560-199600001-00027 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VG828 UT WOS:A1996VG82800027 PM 8797721 ER PT J AU Goldman, AI Carlin, BP Crane, LR Launer, C Korvick, JA Deyton, L Abrams, DI AF Goldman, AI Carlin, BP Crane, LR Launer, C Korvick, JA Deyton, L Abrams, DI TI Response of CD4 lymphocytes and clinical consequences of treatment using ddI or ddC in patients with advanced HIV infection SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE surrogate marker; didanosine; zalcitabine; ZDV failure; ZDV intolerance ID IMMUNODEFICIENCY-VIRUS INFECTION; CONTROLLED TRIAL; ZIDOVUDINE; PROGRESSION; THERAPY; MODELS AB The value of CD4 lymphocyte counts as a surrogate marker in persons with advanced human immunodeficiency virus infection during antiretroviral treatment was assessed using longitudinal models and data from the Terry Beirn Community Programs for Clinical Research on AIDS didanosine/zalcitabine trial of 467 HIV-infected patients. Patients with AIDS or two CD4 counts of less than or equal to 300 who fulfilled specific criteria for zidovudine intolerance or failure were randomized to receive either 500 mg didanosine (ddI) daily or 2.25 mg zalcitabine (ddC) per day. Absolute CD4 counts were recorded at study entry and at as many as four visits. Patients were followed for clinical disease progression and survival. At 2 months, the difference in mean CD4 count from baseline was + 15.4 cells/mm(3) in the ddI group but - 1.3 cells/mm(3) in the ddC group. Patients assigned to ddI had a greater chance of a CD4 response at 2 months than those on ddC, yet only those in the ddC group with a response showed significant improvement in progression of disease or survival compared with ddC nonresponders, ddI responders, and ddI nonresponders (p = 0.03). We conclude that a CD4 response does not necessarily correlate with improved outcome and is therefore not a useful surrogate marker in these patients. C1 US FDA,ANTIRETROVIRAL DRUG PROD,ROCKVILLE,MD 20857. NIAID,DIV AIDS,BETHESDA,MD 20892. WAYNE STATE UNIV,DETROIT MED CTR,HIV AIDS PROGRAM,DETROIT,MI. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO COMMUN CONSORTIUM AIDS,SAN FRANCISCO,CA 94143. RP Goldman, AI (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,BOX 303,MAYO MEM BLDG,MINNEAPOLIS,MN 55455, USA. FU NIAID NIH HHS [N01-AI05073, 1-R29-AI33466] NR 19 TC 25 Z9 27 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PY 1996 VL 11 IS 2 BP 161 EP 169 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TR348 UT WOS:A1996TR34800007 PM 8556398 ER PT J AU Biggar, RJ Melbye, M AF Biggar, RJ Melbye, M TI Marital status in relation to Kaposi's sarcoma, non-Hodgkin's lymphoma, and anal cancer in the pre-AIDS era SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE Kaposi's sarcoma; non-Hodgkin's lymphoma; anal cancer; marital status ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HOMOSEXUAL MEN; ASSOCIATION AB Persons with human immunodeficiency virus/AIDS are at high risk of Kaposi's sarcoma (KS), non-Hodgkin lymphoma (NHL), and possibly anal cancers. To examine whether this risk preceded the AIDS epidemic, we used pre-AIDS era data from the Surveillance, Epidemiology, and End Results program (excluding Connecticut) from 1973 to 1976, and the Connecticut Tumor Registry from 1940 to 1976. We compared risk of being single (a surrogate to identify men who might be homosexual) to those ever married, using a case control matching study with up to 10 controls per case. Overall, no excess risk was observed for KS (risk ratio for men 20-59 years old: 1.00; 95% confidence interval 0.218-3.61), but there was a suggestion of higher risk (4.00; 0.54-29.48) in 1973-1976, the period just before the AIDS epidemic. The NHL risk (0.85; 0.74-0.99) was slightly low, but for anal cancer the risk ratio of being single was significantly high both in men 20-59 years old (5.68) and older men (2.78) long before the AIDS epidemic. If the excess risk was solely due to being homosexual, the actual relative risk in the subset who were homosexual must have been much higher, given that only a fraction of the single men would have been homosexual. As comparison groups to verify the methodology, we used colon (no association with marital status) and prostatic cancer (decreased in single men), with findings as reported in other studies. Thus, single men may have been at an excess risk of KS (but a slightly low risk of NHL) just before the AIDS epidemic and have been at excess risk of anal cancer for many years before the AIDS epidemic. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. STATE SERUM INST,DANISH EPIDEMIOL SCI CTR,COPENHAGEN,DENMARK. NR 24 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PY 1996 VL 11 IS 2 BP 178 EP 182 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TR348 UT WOS:A1996TR34800009 PM 8556400 ER PT J AU Klausner, JD Makonkawkeyoon, S Akarasewi, P Nakata, K Kasinrerk, W Corral, L Dewar, RL Lane, HC Freedman, VH Kaplan, G AF Klausner, JD Makonkawkeyoon, S Akarasewi, P Nakata, K Kasinrerk, W Corral, L Dewar, RL Lane, HC Freedman, VH Kaplan, G TI The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M-tuberculosis infection SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE human immunodeficiency syndrome type 1; tuberculosis; tumor necrosis factor alpha (TNF-alpha); thalidomide; wasting ID TUMOR-NECROSIS-FACTOR; ERYTHEMA-NODOSUM LEPROSUM; T-CELL CLONE; FACTOR-ALPHA; TNF-ALPHA; EXPRESSION; AIDS; INDUCTION; REPLICATION; CACHEXIA AB Tumor necrosis factor alpha (TNF-alpha), a cytokine produced during the host defense against infection, is associated with fevers, weakness, and progressive weight loss. Thalidomide inhibits the synthesis of TNF-alpha both in vitro and in vivo and may have clinical usefulness. We therefore initiated a pilot study of thalidomide treatment in patients with human immunodeficiency virus type 1 (HIV-1)-associated wasting with or without concomitant infection with tuberculosis. Thirty-nine patients were randomly allocated to treatment with either thalidomide or placebo in a double-blind manner for 21 days. Thirty-two patients completed the study. In patients with concomitant HIV-1 and tuberculosis infections, thalidomide therapy was associated with a reduction in both plasma TNF-alpha levels and HIV-1 levels. No significant reduction in either TNF-alpha or HIV-1 levels was observed in patients with HIV-1 infection only. During the study period, patients receiving thalidomide treatment (n = 16) showed a significant weight gain (mean +/- SEM: 6.5 +/- 1.2%; p < 0.02) relative to placebo-treated patients (n = 16). Patients with simultaneous HIV-1 and tuberculosis infections experienced a higher mean weight gain during thalidomide treatment than the group of patients with HIV-1 infection only. The results of this pilot study suggest that thalidomide may have a clinical role in enhancing weight gain and possibly reducing TNF-alpha and HIV-1 levels in patients with HIV-1 and concomitant mycobacterial infections. C1 ROCKEFELLER UNIV,CELLULAR PHYSIOL & IMMUNOL LAB,NEW YORK,NY 10021. NIAID,NIH,BETHESDA,MD 20892. CELGENE CORP,WARREN,NJ. CHIANG MAI UNIV,DEPT MICROBIOL,CHIANG MAI 50000,THAILAND. CHIANG MAI UNIV,FAC MED,CHIANG MAI 50000,THAILAND. CHIANG MAI ANTI TB ASSOC,CHIANG MAI,THAILAND. NYU,MED CTR,DEPT MED,NEW YORK,NY. NYU,MED CTR,DEPT PULM & CRIT CARE MED,NEW YORK,NY. FU NIAID NIH HHS [AI24775, AI33124] NR 33 TC 149 Z9 152 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PY 1996 VL 11 IS 3 BP 247 EP 257 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TZ110 UT WOS:A1996TZ11000005 PM 8603261 ER PT J AU Craig, TJ Moeckli, JK Mawhorter, SD AF Craig, TJ Moeckli, JK Mawhorter, SD TI Splenomegaly in idiopathic hypereosinophilic syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 NIH,BETHESDA,MD. RP Craig, TJ (reprint author), UNIV IOWA,200 HAWKINS DR,IOWA CITY,IA 52242, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1996 VL 97 IS 1 BP 139 EP 140 DI 10.1016/S0091-6749(96)70299-3 PN 1 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA TR947 UT WOS:A1996TR94700024 PM 8568132 ER PT J AU Marshall, JS Rivera, J Hewlett, B Stead, R Shaikh, N AF Marshall, JS Rivera, J Hewlett, B Stead, R Shaikh, N TI Fc epsilon R1 beta-subunit expression is enhanced by in vivo administration of IgE in rats. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1996 VL 97 IS 1 BP 328 EP 328 PN 3 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA TV536 UT WOS:A1996TV53600328 ER PT J AU Druey, KM Tuscano, JM Riva, A Pena, J Thompson, CB AF Druey, KM Tuscano, JM Riva, A Pena, J Thompson, CB TI bcl-x rather than bcl-2 promotes cell survival during centrocyte selection in the germinal center. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1996 VL 97 IS 1 BP 980 EP 980 PN 3 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA TV536 UT WOS:A1996TV53600980 ER PT J AU Magae, J Miller, MW Nagai, K Shearer, GM AF Magae, J Miller, MW Nagai, K Shearer, GM TI Effect of metacycloprodigiosin, an inhibitor of killer T cells, on murine skin and heart transplants SO JOURNAL OF ANTIBIOTICS LA English DT Article ID MEDIATING ALLOGRAFT-REJECTION; PRODIGIOSIN 25-C; SUPPRESSION; SPLENOCYTES; MECHANISMS; INDUCTION; SUBSETS; INVIVO AB Metacycloprodigiosin is an antibiotic that has been shown to suppress T-cell proliferation induced by concanavalin A in vitro. We examined the effect of metacycloprodigiosin on murine allogeneic skin and heart transplantation models, and compared graft rejection with donor-specific cytotoxic T-cells and antibody activity. The antibiotic slightly prolonged the survival of C57B1/6 heart and skin grafts in BALB/c mice, although the effect was less than that of cyclosporin A. The effect was more evident in Bm1 (H-2D mutant) skin grafts on C57B1/6 hosts or in a minor histocompatibility antigen-mismatched model. In contrast, metacycloprodigiosin suppressed anti-graft cytotoxic T-cell activity of BALB/c spleen grafted with C57B1/6 skin as comparable to cyclosporin A, but had only partial effect on antibody production. Thus, metacycloprodigiosin is more effective in reducing splenic cytotoxic T-cell activity than in prolonging murine skin or cardiac allografts. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. TOKYO INST TECHNOL,DEPT BIOENGN,MIDORI KU,YOKOHAMA,KANAGAWA 227,JAPAN. NR 32 TC 40 Z9 43 U1 0 U2 2 PU JAPAN ANTIBIOT RES ASSN PI TOKYO PA 2 20 8 KAMIOSAKI SHINAGAWA KU, TOKYO 141, JAPAN SN 0021-8820 J9 J ANTIBIOT JI J. Antibiot. PD JAN PY 1996 VL 49 IS 1 BP 86 EP 90 PG 5 WC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy GA TR597 UT WOS:A1996TR59700016 PM 8609093 ER PT J AU Lei, PS Ogawa, Y Kovac, P AF Lei, PS Ogawa, Y Kovac, P TI New N-acylating reagents derived from 3-deoxy-L-glycero-tetronic acid SO JOURNAL OF CARBOHYDRATE CHEMISTRY LA English DT Article ID LIPOPOLYSACCHARIDE; ALCOHOLS AB Commercially available N-Boc-4-O-benzyl-L-homoserine was treated with trifluoroacetic acid and the corresponding, N-deprotected derivative was submitted to deamination to give 4-O-benzyl-3-deoxy-L-glycero-tetronic acid (5). In another approach to 3-deoxy-L-glycero-tetronic acid protected at position 4, the carboxylic groups in L-malic acid were reduced, and the resulting triol was benzylidenated. Oxidation of the 2,4-O-benzylidene derivative formed with CrO3-pyridine complex in the presence of t-butyl alcohol gave t-butyl 2,4-O-benzylidene-3-deoxy-L-glycero-tetronate (13). The latter was saponified with aqueous sodium hydroxide to give, after Na+ exchange for H+, 2,4-O-benzylidene-3-deoxy-L-glycero-tetronic acid (15). Opening of the acetal ring in 13, followed by hydrolytic cleavage of the t-butyl ester function gave material indistinguishable from 5 obtained in the original way. When tested for their efficiency of N-acylation of derivatives of D-perosamine, both acids 5 and 15 gave the corresponding tetronamido derivatives in high yields. C1 NIDDK,NIH,BETHESDA,MD 20892. NR 24 TC 14 Z9 14 U1 1 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8303 J9 J CARBOHYD CHEM JI J. Carbohydr. Chem. PY 1996 VL 15 IS 4 BP 485 EP 500 DI 10.1080/07328309608005668 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA UP004 UT WOS:A1996UP00400008 ER PT J AU Cottam, DW Corbitt, RH Gomez, DE Rees, RC Thorgeirsson, UP AF Cottam, DW Corbitt, RH Gomez, DE Rees, RC Thorgeirsson, UP TI Alterations in endothelial cell proteinase and inhibitor polarized secretion following treatment with interleukin-1, phorbol ester, and human melanoma cell conditioned medium SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE endothelium; polarization; proteinases; IL-1 alpha ID TUMOR-NECROSIS-FACTOR; PLASMINOGEN-ACTIVATOR INHIBITORS; IV COLLAGENASE; EXTRACELLULAR-MATRIX; TISSUE INHIBITOR; GENE-EXPRESSION; METASTASIS; METALLOPROTEINASES; MEMBRANE; CANCER AB Polarized secretion of matrix metalloproteinases and plasminogen activators by monkey aortic endothelial cells was studied in vitro, using transwell inserts. The endothelial cells constitutively expressed matrix metalloproteinase-2, tissue inhibitors of metalloproteinases 1 and 2, urokinase, and tissue plasminogen activator, all with basal preference. Matrix metalloproteinase-9 activity was induced by phorbol 12-myristate 13-acetate (apical), interleukin-1 alpha (basal), and by conditioned medium from DX3 human melanoma cells (basal). The DX3 melanoma conditioned medium also stimulated basal secretion of matrix metalloproteinase-2, urokinase, tissue plasminogen activator, and tissue inhibitors of metalloproteinases. The rise in proteolytic activity in the basal direction was reflected by increased capacity to degrade subendothelial basement membrane type IV collagen, shown immunohistologically, using monkey kidney tissue sections and basement membrane deposited by endothelial cells into the transwell membrane. Thus, IL-1 alpha and DX3 melanoma conditioned medium can stimulate endothelial cells in vitro to concentrate secretion of proteinases spatially onto the underlying basement membrane. We suggest that the stimulation of endothelial cell proteinase activity by tumor cells may facilitate tumor cell extravasation. (C) 1996 Wiley-Liss, Inc.* C1 NCI,NIH,TUMOR BIOL & CARCINOGENESIS SECT,OFF DIRECTOR,DIV CANC ETIOL,BETHESDA,MD 20892. UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,SHEFFIELD S10 2RX,S YORKSHIRE,ENGLAND. OI Gomez, Daniel E/0000-0002-8629-0787 NR 49 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN PY 1996 VL 60 IS 1 BP 148 EP 160 DI 10.1002/(SICI)1097-4644(19960101)60:1<148::AID-JCB17>3.0.CO;2-L PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TT662 UT WOS:A1996TT66200017 PM 8825424 ER PT J AU Kelloff, GJ Boone, CW Crowell, JA Steele, VE Lubet, RA Doody, LA Malone, WF Hawk, ET Sigman, CC AF Kelloff, GJ Boone, CW Crowell, JA Steele, VE Lubet, RA Doody, LA Malone, WF Hawk, ET Sigman, CC TI New agents for cancer chemoprevention SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Review DE cancer chemopreventive agents; drug development; retinoids; DFMO; NSAIDs; oltipraz; Phase I clinical trials; Phase II clinical trials ID TYROSINE-KINASE INHIBITOR; 9-CIS RETINOIC ACID; SYNTHETIC ORGANOSELENIUM COMPOUND; MONOTERPENE PERILLYL ALCOHOL; SPRAGUE-DAWLEY RATS; VITAMIN-D ANALOGS; ORNITHINE DECARBOXYLASE ACTIVITY; OCCURRING ORGANOSULFUR COMPOUNDS; COLONIC ADENOCARCINOMA CELLS; MAMMARY-GLAND CARCINOGENESIS AB Clinical chemoprevention trials of more than 30 agents and agent combinations are now in progress or being planned. The most advanced agents are well known and are in large Phase III chemoprevention intervention trials or epidemiological studies. These drugs include several retinoids [e.g., retinol, retinyl palmitate, all-trans-retinoic acid, and 13-cis-retinoic acid], calcium, beta carotene, vitamin E, tamoxifen, and finasteride. Other newer agents are currently being evaluated in or being considered for Phase II and early Phase III chemoprevention trials. Prominent in this group are all-trans-N-(4-hydroxy phenyl)retinamide (4-HPR) (alone and in combination with tamoxifen), 2-difluoromethylornithine (DFMO), nonsteroidal antiinflammatory drugs (aspirin, piroxicam, sulindac), oltipraz, and dehydroepiandrostenedione (DHEA). A third group is new agents showing chemopreventive activity in animal models, epidemiological studies, or in pilot clinical intervention studies. They are now in preclinical toxicology testing or Phase I safety and pharmacokinetics trials preparatory to chemoprevention efficacy trials. These agents include S-allyl-l-cysteine, curcumin, DHEA analog 8354 (fluasterone), genistein, ibuprofen, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, sulindac sulfone, tea extracts, ursodiol, vitamin D analogs, and p-xylyl selenocyanate. A new generation of agents and agent combinations will soon enter clinical chemoprevention studies based primarily on promising chemopreventive activity in animal models and in mechanistic studies. Among these agents are more efficacious analogs of known chemopreventive drugs including novel carotenoids (e.g., alpha-carotene and lutein). Also included are safer analogs which retain the chemopreventive efficacy of the parent drug such as vitamin D-3 analogs. Other agents of high interest are aromatase inhibitors (e.g., (+)-vorozole), and protease inhibitors (e.g., Bowman-Birk soybean trypsin inhibitor). Combinations are also being considered, such as vitamin E with l-selenomethionine. Analysis of signal transduction pathways is beginning to yield classes of potentially active and selective chemopreventive drugs. Examples are ras isoprenylation and epidermal growth factor receptor inhibitors. C1 CCS ASSOCIATES, MT VIEW, CA 94043 USA. RP NCI, CHEMOPREVENT LAB, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. NR 409 TC 1 Z9 1 U1 0 U2 0 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 1996 SU 26 BP 1 EP 28 PG 28 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WX846 UT WOS:A1996WX84600002 ER PT J AU Kelloff, GJ Boone, CW Crowell, JA Nayfield, SG Hawk, E Malone, WF Steele, VE Lubet, RA Sigman, CC AF Kelloff, GJ Boone, CW Crowell, JA Nayfield, SG Hawk, E Malone, WF Steele, VE Lubet, RA Sigman, CC TI Risk biomarkers and current strategies for cancer chemoprevention SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Prospects for Chemoprevention in Cohorts with Cancer Risk Markers CY OCT 05-07, 1995 CL EASTON, MD SP Natl Canc Inst, Div Canc Prevent Control, Chemoprevent Branch DE chemoprevention; genetic/regulatory biomarkers; high-risk cohorts; intraepithelial neoplasia; phase II clinical trials, risk biomarkers ID TUMOR-SUPPRESSOR GENE; OVARIAN-CANCER; MOLECULAR DOSIMETRY; BREAST-CANCER; LUNG-CANCER; INTRAEPITHELIAL NEOPLASIA; FAMILIAL BREAST; BLADDER-CANCER; UNITED-STATES; RATS AB Quantifiable, well-characterized cancer risk factors demonstrate the need for chemoprevention and define cohorts for chemopreventive intervention. For chemoprevention, the important cancer risk factors are those that can be measured quantitatively in the subject at risk. These factors, called risk biomarkers, can be used to identify cohorts for chemoprevention. Those modulated by chemopreventive agents may also be used as endpoints in chemoprevention studies. Generally, the risk biomarkers fit into categories based on those previously defined by Hulka: 1) carcinogen exposure, 2) carcinogen exposure/effect, 3) genetic predisposition, 4) intermediate biomarkers of cancer, and 5) previous cancers. Besides their use in characterizing cohorts for chemoprevention trials, some risk biomarkers can be modulated by chemopreventive agents. These biomarkers may be suitable surrogate endpoints for cancer incidence in chemoprevention intervention trials. The criteria for risk biomarkers defining cohorts and serving as endpoints are the same, except that those defining cohorts are not necessarily modulated by chemopreventive agents. A primary criterion is that the biomarkers fit expected biological mechanisms of early carcinogenesis-i.e., differential expression in normal and high-risk tissue, on or closely linked to the causal pathway for the cancer, and short latency compared with cancer. They must occur in sufficient number to allow their biological and statistical evaluation. Further, the biomarkers should be assayed reliably and quantitatively, measured easily, and correlated to cancer incidence. Particularly important for cancer risk screening in normal subjects is the ability to use noninvasive techniques that are highly specific, sensitive, and quantitative. Since carcinogenesis is a multipath process, single biomarkers are difficult to correlate to cancer, as they may appear on only one or a few of the many possible causal pathways. As shown in colorectal carcinogenesis, the risks associated with the presence of biomarkers may be additive or synergistic. That is, the accumulation of genetic lesions is the more important determinant of colorectal cancer compared with the presence of any single lesion. Thus, batteries of biomarker abnormalities, particularly those representing the range of carcinogenesis pathways, may prove more useful than single biomarkers both in characterizing cohorts at risk and defining modulatable risks. Risk biomarkers are already being integrated into many chemoprevention intervention trials. One example is the phase II trial of oltipraz inhibition of carcinogen-DNA adducts in a Chinese population exposed to aflatoxin B-1. Also, urine samples from subjects in this trial will be screened for the effect of oltipraz on urinary mutagens. A second example is a chemoprevention protocol developed for patients at high risk for breast cancer; the cohort is defined both by hereditary risk and the presence of biomarker abnormalities. Modulation of the biomarker abnormalities is a proposed endpoint. Also, dysplastic lesions, such as prostatic intraepithelial neoplasia, oral leukoplakia and colorectal adenomas, have been used to define high-risk cohorts and as potential modulatable surrogate endpoints in chemoprevention trials. (C) 1997 Wiley-Liss, Inc.(dagger) C1 CCS ASSOCIATES, MT VIEW, CA USA. RP Kelloff, GJ (reprint author), NCI, CHEMOPREVENT BRANCH,DCPC,NIH,9000 ROCKVILLE PIKE, EPN SUITE 201, BETHESDA, MD 20892 USA. NR 73 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 25 BP 1 EP 14 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WG728 UT WOS:A1996WG72800002 ER PT J AU Oie, HK Russell, EK Carney, DN Gazdar, AF AF Oie, HK Russell, EK Carney, DN Gazdar, AF TI Cell culture methods for the establishment of the NCI series of lung cancer cell lines SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE lung cancer cell lines; cell culture techniques; SErum-free; defined medium ID FREE DEFINED MEDIUM; SERUM; GROWTH; CARCINOMA AB More than 200 human small cell lung cancer and non-smalt cell lung cancer cell lines were established over 15 years mainly by utilizing the serum-free, hormone and growth factor supplemented, defined media HITES and ACL4. Use of modified, established cell culture techniques such as the mechanical spillout method for the releasing of cell aggregates from tumor tissue, ficoll gradient centrifugation for the separation of tumor cells from erythrocytes and tissue debris, and an apparatue consisting of a platinum tubing attached to a suction flask for removal of spent medium have greatly contributed to the success in culturing tumor cells. Characterization of these lung cancer cell lines have extended our knowledge of lung cell biology. Studies elucidating the nutritional requirements of lung cancer cell growth may be helpful for the manipulation of these tumors in patients. (C) 1996 Wiley-Liss, Inc. C1 NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. MATER MISERICORDIAE HOSP, DEPT MED ONCOL, DUBLIN 7, IRELAND. UNIV TEXAS, SW MED CTR, DALLAS, TX 75235 USA. RP Oie, HK (reprint author), NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20814 USA. NR 22 TC 18 Z9 18 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 24 EP 31 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300005 ER PT J AU Greenwald, P AF Greenwald, P TI Cancer risk factors for selecting cohorts for large-scale chemoprevention trials SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Prospects for Chemoprevention in Cohorts with Cancer Risk Markers CY OCT 05-07, 1995 CL EASTON, MD SP Natl Canc Inst, Div Canc Prevent Control, Chemoprevent Branch DE biomarkers; cancer risk assessment; gene-environment interactions; large-scale trials; prevention trials decision network; twin studies ID HODGKINS-DISEASE; SPONTANEOUS TUMORIGENESIS; GENETIC SUSCEPTIBILITY; PROSTATE-CANCER; PREVENTION; CONCORDANCE; FENRETINIDE; BREAST; TWINS; MICE AB Many anticipate that application of findings in molecular genetics will help to achieve greater precision in defining high-risk populations that may benefit from chemopreventive interventions. We must recognize, however, that genetic susceptibility, environmental factors, and complex gene-environment interactions are all likely to be risk determinants for most cancers. Cohort studies of twins and cancer indicate that having ''identical'' genes is generally not a very accurate predictor of cancer incidence. Data from twin studies support the suggestion that environmental factors such as tobacco use significantly influence cancer risk. The complexities of the genetic contribution to disease risk are exemplified by the development of Duchenne muscular dystrophy in only one of monozygotic twin girls, hypothesized to be the result of X chromosome inactivation, with the distribution patterns of the X chromosome being skewed to the female X in the manifesting twin and to the male X in the normal twin. Evidence from transgenic and genetic-environmental studies in animals support the possibility of genetic-environmental interactions. Calorie restriction modifies tumor expression in p53 knockout mice; a high-fat, low-calcium, low-vitamin D diet increases prepolyp hyperplasia formation in Ape-mutated mice; and calorie restriction early in life influences development of obesity in the genetically obese Zucker rat (fafa). Such environmental modulation of gene expression suggests that chemoprevention has the potential to reduce risk for both environmentally and genetically determined cancers. In view of the growing research efforts in chemoprevention, the NCI has developed a Prevention Trials Decision Network (PTDN) to formalize the evaluation and approval process for large-scale chemoprevention trials. The PTDN addresses large trial prioritization and the associated issues of minority recruitment and retention; identification and validation of biomarkers as intermediate endpoints for cancer; and chemopreventive agent selection and development. A comprehensive database is being established to support the PTDN's decision-making process and will help to determine which agents investigated in preclinical and early phase clinical trials should move to large-scare testing. Cohorts for large-scale chemoprevention trials include individuals who are determined to be at high risk as a result of genetic predisposition, carcinogenic exposure, or the presence of biomarkers indicative of increased risk. Current large-scale trials in well-defined, high-risk populations include the Breast Cancer Prevention Trial (tamoxifen), the Prostate Cancer Prevention Trial (finasteride), and the N-(4-hydroxyphenyl) retinamide (4-HPR) breast cancer prevention study being conducted in Milan. Biomarker studies will provide valuable information for refining the design and facilitating the implementation of future large-scale trials. For example, potential biomarkers are being assessed at biopsy in women with ductal carcinoma in situ (DCIS). The women are then randomized to either placebo, tamoxifen, 4-HPR, or tamoxifen plus 4-HPR for 2-4 weeks, at which time surgery is performed and the biomarkers reassessed to determine biomarker modulation by the interventions. For prostate cancer, modulation oi. prostatic intraepithelial neoplasia (PIN) by 4-HPR and difluoromethylornithine is being investigated; similar studies are being planned for oltipraz, dehydroepiandrosterone, and vitamin E plus selenomethionine. The validation of biomarkers as surrogate endpoints for cancer incidence in high-risk cohorts will allow more agents to be evaluated in shorter studies that use fewer subjects to achieve the desired statistical power. (C) 1997 Wiley-Liss, Inc.(dagger) C1 NCI,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892. NR 37 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 25 BP 29 EP 36 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WG728 UT WOS:A1996WG72800005 ER PT J AU Steele, VE Sharma, S Mehta, R Elmore, E Redpath, JL Rudd, C Bagheri, D Sigman, CC Kelloff, GJ AF Steele, VE Sharma, S Mehta, R Elmore, E Redpath, JL Rudd, C Bagheri, D Sigman, CC Kelloff, GJ TI Use of in vitro assays to predict the efficacy of chemopreventive agents in whole animals SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE chemoprevention; carcinogenesis; in vitro assays; animal models ID ANCHORAGE-INDEPENDENT GROWTH; MOUSE EPIDERMAL-CELLS; MAMMARY-GLAND INVITRO; EPITHELIAL-CELLS; DRUG DEVELOPMENT; ORGAN-CULTURE; TRANSFORMATION; INHIBITION; RETINOIDS; CARCINOGENESIS AB Five in vitro assays have been applied to screen the efficacy of potential chemopreventive agents. These assays measure a) inhibition of morphological transformation in rat tracheal epithelial (RTE) cells, b) inhibition of anchorage independence in human lung tumor (A427) cells, c) inhibition of hyperplastic alveolar nodule formation in mouse mammary organ cultures (MMOC), d) inhibition of anchorage independence in mouse JB6 epidermal cells, and e) the inhibition of calcium tolerance in human foreskin epithelial cells. The efficacy of many of these same agents in whole animal studies of lung, colon, mammary gland, skin, and urinary bladder carcinogenesis has also been measured. The aim herein is to estimate the positive and negative predictive values of these in vitro assays against whole animal chemopreventive efficacy data using the same chemicals. For three of these assays-using RTE, A427 cells and mouse mammary organ culture (MMOC)-enough data are available to allow the estimate to be made. Such extrapolations of in vitro data to the in vivo situation are difficult at best. There are many dissimilarities between the two assay systems. The in vitro assays use respiratory and mammary epithelial cells, while the in vivo assays use respiratory, mammary, colon, bladder and skin cells. The in vitro assays use the carcinogens benzo(a)pyrene (B(a)P) and 7,12-dimethylbenz(a)anthracene (DMBA), while the in vivo assays use B(a)P, DMBA, N-methyl-N-nitrosourea (MNU), N,N'-diethylnitrosamine (DEN), azoxymethane (AOM), and N-butyl-N-(4-hydroxybutyl)nitrosoamine (OH-BBN). There are vast differences in pharmacodynamics and pharmacokinetics in vitro and in vivo, yet it is possible to rapidly screen chemicals in vitro for efficacy at one-tenth the cost and complete tests in weeks instead of months. A positive in vitro assay was defined as a 20% inhibition (compared with control) for the RTE and A427 assays and a 60% inhibition for the MMOC assay at nontoxic concentrations. For in vivo assays, the criterion for a positive result was a statistically significant inhibition of incidence, multiplicity or a significant increase in latency (mean time to first tumor). For an agent to be considered negative in animals, it required negative results in at least two different organ systems and no positive results. Using the battery of three in vitro tests, the positive predictive value for having one, two, or three positive in vitro assays and at least one positive whole animal test was 76%, 80%, and 83% respectively. The negative predictive values for one, two or all three in vitro assays was 25%, 27%, and 50%. From these data it is observed that in vitro assays give valuable positive predictive values and less valuable negative predictive values. The mechanisms of chemoprevention are not well understood. Seven categories of agents were examined for their cancer preventing activity both in vitro and in vivo: antiinflammatories, antioxidants, arachadonic acid metabolism inhibitors, GSH inducers, GST inducers, ODC inhibitors, and PKC inhibitors. Three or even five in vitro assays cannot be all-inclusive of the many mechanisms of cancer prevention. However, three assays help to predict whole animal efficacy with reasonable positive predictive values. Much work and development remains to be done to rapidly identify new chemopreventive drugs. C1 MANTECH ENVIRONM TECHNOL INC,RES TRIANGLE PK,NC 27709. UNIV ILLINOIS,COLL MED,SPECIALIZED CANC CTR,CHICAGO,IL 60612. UNIV CALIF IRVINE,IRVINE,CA 92715. SRI INT,MENLO PK,CA 94025. CCS ASSOCIATES,MT VIEW,CA 94043. RP Steele, VE (reprint author), NCI,CHEMOPREVENT LAB,DIV CANC PREVENT & CONTROL,NIH,9000 ROCKVILLE PIKE,EXECUT PLAZA N,SUITE 201,BETHESDA,MD 20892, USA. NR 28 TC 9 Z9 9 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 26 BP 29 EP 53 PG 25 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WX846 UT WOS:A1996WX84600003 ER PT J AU Phelps, RM Johnson, BE Ihde, DC Gazdar, AF Carbone, DP Linnoila, PRMRI Matthews, MJ Bunn, PA Carney, D Minna, JD Mulshine, JL AF Phelps, RM Johnson, BE Ihde, DC Gazdar, AF Carbone, DP Linnoila, PRMRI Matthews, MJ Bunn, PA Carney, D Minna, JD Mulshine, JL TI NCI-Navy Medical Oncology Branch cell line data base SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE cell lines; clinical correlation; in vitro data; polymorphic markers; lung cancer ID FREE DEFINED MEDIUM; LUNG-CANCER; BRONCHOGENIC-CARCINOMA; CLINICAL SPECIMENS; CHEMOTHERAPY; GROWTH; THERAPY; INVITRO; TRIAL AB The cell line data base described in this paper includes both clinical information about the patients from whom the cell lines were derived and information about the in vitro analyses performed of the cell lines. The cell line data base has evolved as a part of a systematic effort by a research group at the NCl since 1976 to generate human cell lines as biological toots to study cancer and other diseases. The cell lines were generated from clinical specimens obtained as part of a series of Institutional Review Board-approved clinical protocols, The preponderance of the data is on lung cancer cell lines, though a broad range of other cancers are represented. A bank of over 300 human cell lines including cancer cell and in some instances autologous B-lymphoblastoid cells from the NCI-VA and NCI-Navy Medical Oncology Branch are reposited at the American Type Culture Collection. The cell lines are available for the research community. The entire database is available on the American Type Culture Collection Web Site (WWW:http://www.atcc.org/). (C) 1996 Wiley-Liss, Inc.* C1 NATL NAVAL MED CTR, NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20897 USA. AMER TYPE CULTURE COLLECT, ROCKVILLE, MD 20852 USA. NR 16 TC 56 Z9 57 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 32 EP 91 PG 60 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300006 ER PT J AU Gould, MN Lubet, RA Kelloff, GJ Haag, JD AF Gould, MN Lubet, RA Kelloff, GJ Haag, JD TI Inherited susceptibility and acquired allelic imbalance in rat mammary carcinogenesis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Prospects for Chemoprevention in Cohorts with Cancer Risk Markers CY OCT 05-07, 1995 CL EASTON, MD SP Natl Canc Inst, Div Canc Prevent Control, Chemoprevent Branch DE mammary cancer; cancer genetics; epigenetic; chemoprevention ID CARCINOMA SUPPRESSOR GENE; EXPRESSION; MODEL; SITE AB Individual genetically determined susceptibility to cancer as well as acquired epigenetic and genetic organ specific alterations are important considerations in choosing target populations for chemopreventive trials. These individual epigenetic and generic alterations can also serve as potential biomarkers for chemoprevention clinical trials. In order to model these potential markers for chemoprevention investigations, we are examining a series of interrelated rat models. Inbred rats vary in their susceptibility to mammary cancer induction by environmental agents. For example, the WF strain is highly susceptible to chemically induced mammary cancer while the Cop rdt is almost completely resistant. The F344 is intermediate in susceptibility to chemically induced mammary cancer. These differential susceptibilities are inherited in a dominant pattern. For example, resistance is due to the inheritance of Mcs gene(s) which likely act by altering the differentiation lineage of mammary epithelial cells. As tumors form in the mammary glands of these rats, they acquire additional epigenetic and genetic alterations. Epigenetic initiation is a very frequent cellular event following carcinogen exposure which may predispose cells to genetic change including allelic imbalance. For example, following a standard dose of NMU or DMBA over 1% of cells are epigenetically initiated. During the carcinogenesis process, initialed cells may acquire genetic change such as oncogene activation and allelic imbalance. Interestingly, the pattern of allelic imbalance appears to be an inherited trait. For example, a non-random loss of heterozygosity (LOH) in rat chromosome 1 following DMBA only occurs in certain strains, such as Cop rats. Interestingly this change does not occur following initiation by ionizing radiation. It will thus be important to identify these epigenetic and genetic events which underlie mammary carcinogenesis as well as determine their patterns of inherited predisposition and temporal occurrence. Such knowledge is critical if we are to develop new molecular markers for chemoprevention trials. (C) 1997 Wiley-Liss, Inc. C1 NIH,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD. RP Gould, MN (reprint author), UNIV WISCONSIN,DEPT HUMAN ONCOL,K4-332,600 HIGHLAND AVE,MADISON,WI 53792, USA. RI Gould, Michael/C-7414-2014 NR 11 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 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 25 BP 37 EP 40 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WG728 UT WOS:A1996WG72800006 ER PT J AU Liu, JF Wang, Y Gu, P Patrick, J Crist, KA Sabourin, CLK Stoner, GD Mitchell, MF Fanning, JD Kim, K Goldblatt, PJ Kelloff, GJ Boone, CW You, M AF Liu, JF Wang, Y Gu, P Patrick, J Crist, KA Sabourin, CLK Stoner, GD Mitchell, MF Fanning, JD Kim, K Goldblatt, PJ Kelloff, GJ Boone, CW You, M TI Detection of genomic alterations in human cervical cancer by two-dimensional gel electrophoresis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Prospects for Chemoprevention in Cohorts with Cancer Risk Markers CY OCT 05-07, 1995 CL EASTON, MD SP Natl Canc Inst, Div Canc Prevent Control, Chemoprevent Branch DE two-dimensional gel electrophoresis; cervical cancer; genomic alterations; genomic scanning; chemoprevention ID SQUAMOUS-CELL CARCINOMA; RAS ONCOGENE EXPRESSION; TUMOR-SUPPRESSOR GENE; UTERINE CERVIX; DNA METHYLATION; SCANNING METHOD; INTRAEPITHELIAL NEOPLASIA; RLGS METHOD; P53; HETEROZYGOSITY AB Two-dimensional gel electrophoresis was used to comprehensively scan the whole genome of 6 cervical intraepithelial neoplasia (CIN) lesions, 7 cervical squamous cell carcinomas, 1 cervical adenosquamous cell carcinoma, and 2 cervical adenocarcinomas for multiple genetic alterations, such as DNA amplification, chromosome deletion, loss of heterozygosity, and chromosome translocation, as compared with the paired normal tissues. DNA spot analysis of the genomic 2-dimensional gels was performed by a computer color overlay system and by spot recognition software allowing for objective spot comparison and quantitation. Nine spots were found to be amplified in the cervical carcinomas while two amplified spots were detected in the CIN III lesions. Fourteen DNA spots were either reduced in their intensity or absent in cervical carcinomas as compared to their normal paired tissues. Reduction of intensity in 6 spots was observed in the 5 CIN III lesions. These genetic alterations may represent changes in cancer genes that are associated with human cervical carcinogenesis. Further characterization of these alterations may be significant to the understanding of cervical tumorigenesis and to the development of biomarkers for clinical trials in cancer chemoprevention. (C) 1997 Wiiey-Liss, Inc. C1 MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43614. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. NCI,NIH,BETHESDA,MD 20892. NR 45 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 25 BP 41 EP 48 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WG728 UT WOS:A1996WG72800007 ER PT J AU Crist, KA Kim, K Goldblatt, PJ Boone, CW Kelloff, GJ You, M AF Crist, KA Kim, K Goldblatt, PJ Boone, CW Kelloff, GJ You, M TI DNA quantification in cervical intraepithelial neoplasia thick tissue sections by confocal laser scanning microscopy SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Prospects for Chemoprevention in Cohorts with Cancer Risk Markers CY OCT 05-07, 1995 CL EASTON, MD SP Natl Canc Inst, Div Canc Prevent Control, Chemoprevent Branch DE cervical intraepithelial neoplasia; confocal microscopy; DNA quantitation ID CELL LUNG-CARCINOMA; ACID-LABILE DNA; PROGNOSTIC FACTORS; BREAST-CARCINOMA; IMAGE CYTOMETRY; BLADDER-CANCER; PLOIDY; CHEMOTHERAPY; SURVIVAL; FEULGEN AB Image analysis of tissue biopsies for determination of DNA content as an early marker of neoplasia is hampered by the complexity of corrections necessary to deal with nuclear truncation and overlap in thin sections. The use of confocal laser scanning microscopy (CLSM) for measurement of cellular DNA content on whole cells within thick tissue sections offers the advantage of preservation of cellular architecture, capacity for 3-dimensional analysis, and absence of sectioning artifacts. We have applied this technique to pararosaniline-feulgen stained human cervical tissues graded from normal to cervical intraepithelial neoplasia (GIN) III. For the purpose of comparison, 15 mu m sections were stained and mapped so that the same cell population could be analyzed by both integrated optical density and fluorescence intensity. Distribution of DNA content from normal cervical epithelial cells 2-3 layers out from the basal cell layer measured by both methodologies showed a stable G0/G1 population with no observable S-phase or G2 cells. Cells measured from areas of increasing CIN grade showed progressively higher DNA content values that were not observable in normal tissue. Although these data are preliminary they suggest that CLSM can be used to identify aneuploid states within defined structural areas of pre-invasive neoplasia. (C) 1997 Wiley-Liss, Inc. C1 MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT INVEST STUDIES BRANCH,NIH,BETHESDA,MD 20892. RP Crist, KA (reprint author), MED COLL OHIO,DEPT SURG,3000 ARLINGTON AVE,TOLEDO,OH 43699, USA. NR 29 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 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 25 BP 49 EP 56 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WG728 UT WOS:A1996WG72800008 ER PT J AU Kelloff, GJ Crowell, JA Hawk, ET Steele, VE Lubet, RA Boone, CW Covey, JM Doody, LA Omenn, GS Greenwald, P Hong, WK Parkinson, DR Bagheri, D Baxter, GT Blunden, M Doeltz, MK Eisenhauer, KM Johnson, K Knapp, GG Longfellow, DG Malone, WF Nayfield, SG Seifried, HE Swall, LM Sigman, CC AF Kelloff, GJ Crowell, JA Hawk, ET Steele, VE Lubet, RA Boone, CW Covey, JM Doody, LA Omenn, GS Greenwald, P Hong, WK Parkinson, DR Bagheri, D Baxter, GT Blunden, M Doeltz, MK Eisenhauer, KM Johnson, K Knapp, GG Longfellow, DG Malone, WF Nayfield, SG Seifried, HE Swall, LM Sigman, CC TI Strategy and planning for chemopreventive drug development: Clinical Development Plans II SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article ID NUTRITION INTERVENTION TRIALS; ADVANCED BREAST-CANCER; FOLIC-ACID; DIETARY INDOLE-3-CARBINOL; URSODEOXYCHOLIC ACID; AROMATASE INHIBITOR; CERVICAL DYSPLASIA; MAMMARY-TUMORS; PHASE-II; SUPPLEMENTATION AB This is the second publication of Clinical Development Plans from the National Cancer Institute, Division of Cancer Prevention and Control, Chemoprevention Branch and Agent Development Committee. The Clinical Development Plans summarize the status of promising chemopreventive agents regarding evidence for safety and chemopreventive efficacy in preclinical and clinical studies. They also contain the strategy for further development of these drugs, addressing pharmacodynamics, drug effect measurements, intermediate biomarkers for monitoring efficacy, toxicity, supply and formulation, regulatory approval, and proposed clinical trials. Sixteen new Clinical Development Plans are presented here: curcumin, dehydroepiandrosterone, folic acid, genistein, indole-3-carbinol, perillyl alcohol, phenethyl isothiocyanate, 9-cis-retinoic acid, 13-cis-retinoic acid, l-selenomethionine and 1,4-phenylenebis(methylene)selenocyanate, sulindac sulfone, tea, ursodiol, vitamin A, and (+)-vorozole. The objective of publishing these plans is to stimulate interest and thinking among the scientific community on the prospects for developing these and future generations of chemopreventive drugs. (C) 1997 Wiley-Liss, Inc. C1 NCI,AGENT WORKING GRP,CHEMOPREVENT BRANCH,DCPC,BETHESDA,MD 20892. NCI,PHARMACOL BRANCH,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20892. CCS ASSOCIATES,MT VIEW,CA 94043. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. NCI,COMMUNITY ONCOL & REHABIL BRANCH,DCPC,BETHESDA,MD 20892. NCI,DIV CANC BIOL,CHEM & PHYS CARCINOGENESIS BRANCH,BETHESDA,MD 20892. RP Kelloff, GJ (reprint author), NCI,AGENT DEV COMM,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. OI Omenn, Gilbert S./0000-0002-8976-6074 NR 30 TC 39 Z9 39 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 26 BP 54 EP 71 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WX846 UT WOS:A1996WX84600004 ER PT J AU Mark, SD AF Mark, SD TI Defining and analyzing cohorts using molecular markers of cancer risk SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Prospects for Chemoprevention in Cohorts with Cancer Risk Markers CY OCT 05-07, 1995 CL EASTON, MD SP Natl Canc Inst, Div Canc Prevent Control, Chemoprevent Branch DE biological markers; cancer; gastric cancer; genetics; log rank test; lung cancer; molecular biology; molecular epidemiology; polymorphisms; p53; prevention; power; sample size; survival analyses; trials ID PRECANCEROUS GASTRIC-LESIONS; SQUAMOUS-CELL CARCINOMA; LUNG; TRIALS AB Cancer is currently regarded to be the phenotypic expression of an accumulation of heritable alterations in the regulators of cell growth and differentiation. Though detailed knowledge of the sequence and in vivo mechanistic effects of these alterations is rudimentary for most, if not all, cancers, their identification does offer the potential for classifying groups of individuals who are heterogeneous with respect to their cancer risks, into more nearly homogeneous subgroups. In this paper, we illustrate the value of using markers, which we define as any manifestation of cellular molecular diversity, to increase subgroup homogeneity. In the context of time-to-event data, we demonstrate for both somatic mutations (acquired p53 abnormalities in gastric mucosal cells) and inherited polymorphisms (polymorphisms in the phase 1 and 2 detoxifying enzymes) how knowledge regarding the population frequency of the marker, the effect of the marker on the risk of cancer development, and/or the effect of the marker on response to therapy, can be used to plan and analyze such trials. Using as paradigms demographic features of the recently begun Shandong precancerous gastric lesion intervention trial, and the recently completed alpha-tocopherol beta-carotene (ATBC) lung cancer prevention study, we review the information, assumptions, and mathematical structure required for planning cancer prevention trials. We graphically demonstrate how informative markers make available strategies for selection, stratification, and optimal weighing, which, when properly implemented, increase the power of rests of effective cancer prevention agents. (C) 1997 Wiley-Liss, Inc.(dagger) RP Mark, SD (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,BIOSTAT BRANCH,EXECUT PLAZA N,ROOM 403,6130 EXECUT BLVD,MSC 7368,BETHESDA,MD 20892, USA. NR 18 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 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 25 BP 69 EP 79 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WG728 UT WOS:A1996WG72800011 ER PT J AU Linnoila, RI AF Linnoila, RI TI Spectrum of neuroendocrine differentiation in lung cancer cell lines featured by cytomorphology, markers, and their corresponding tumors SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE lung cancer cell lines; neuroendocrine differentiation; cytomorphology; markers; tumors ID L-DOPA DECARBOXYLASE; SUPPLEMENTED MEDIUM; GROWTH-PROPERTIES; CARCINOID-TUMORS; CHROMOGRANIN-A; ENDOCRINE; EXPRESSION; INVITRO; IDENTIFICATION; ESTABLISHMENT AB Lung cancer cell lines which show features of neuroendocrine (NE) differentiation can be divided into 4 types which have distinct clinicopathologic correlates: classic small cell lung cancer (SCLC), variant SCLC, pulmonary carcinoid, and non-small cell lung cancer with NE features (NSCLC-NE). These cell lines form a spectrum regarding their degree of NE differentiation which ranges from high levels seen in carcinoid cell lines to very low which is typical of the variant SCLC. A careful comparison of the properties of tumors and their cell lines and correlating these data with the clinical history of the patient has markedly enhanced the relevance of cell lines as models for NE biology and lung carcinogenesis. (C) 1996 Wiley-Liss, Inc.* RP Linnoila, RI (reprint author), NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CLIN SCI,NIH,9610 MED CTR DR,SUITE 300,ROCKVILLE,MD 20850, USA. NR 64 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 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 92 EP 106 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300007 ER PT J AU Nayfield, SG AF Nayfield, SG TI Ethical and scientific considerations for chemoprevention research in cohorts at genetic risk for breast cancer SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Conference on Prospects for Chemoprevention in Cohorts with Cancer Risk Markers CY OCT 05-07, 1995 CL EASTON, MD SP Natl Canc Inst, Div Canc Prevent Control, Chemoprevent Branch DE carcinogenesis; predisposing mutation; malignancy; DNA testing ID OVARIAN-CANCER; SUSCEPTIBILITY GENE; BRCA1 MUTATIONS; FAMILIES; PREVENTION; TAMOXIFEN; WOMEN; EPIDEMIOLOGY; CARRIERS; TRIALS AB Identification of cohorts at genetic risk for cancer offers unique research opportunities to explore the steps in carcinogenesis, from the inheritance of a predisposing mutation to the development of preinvasive lesions or overt malignancy, and to evaluate interventions to modulate the carcinogenic process. However, cancer prevention strategies for most inherited cancer predisposition syndromes are of unproven benefit, and the potential for adverse psychosocial effects and employment or insurance discrimination associated with genetic testing is substantial. Thus testing for genetic cancer risk remains highly controversial, and the National Center for Human Genome Research and the American Society of Human Genetics advise DNA testing for presymptomatic identification of cancer risk only in the setting of a carefully monitored research environment. The commercial availability of predictive genetic resting, particularly for inherited susceptibility to cancer, has focused attention not only on the urgent need for research in cancer prevention for cohorts at genetic cancer risk but also on ethical considerations surrounding clinical prevention research in genetic risk groups. This paper addresses the interrelationship of ethical and scientific issues in conducting chemoprevention research in these cohorts, especially for those studies which require presymptomatic testing for specific gene mutations as a study entry criterion or as a criterion for stratification. Practical approaches to study design and implementation issues for chemoprevention research in genetic risk cohorts are discussed, emphasizing the interactions of ethical and scientific considerations at all levels of the research process. (C) 1997 Wiley-Liss, Inc.(+) RP Nayfield, SG (reprint author), NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,EXECUT PLAZA N,ROOM 201A,BETHESDA,MD 20892, USA. NR 40 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 25 BP 123 EP 130 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WG728 UT WOS:A1996WG72800018 ER PT J AU Pass, HI Mew, DJY AF Pass, HI Mew, DJY TI In vitro and in vivo studies of mesothelioma SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE mesothelioma; cytogenetics; growth factors; oncogenes; asbestos ID HUMAN-MALIGNANT MESOTHELIOMA; CELL-LINES; PLEURAL MESOTHELIOMA; CHROMOSOMAL-ABNORMALITIES; ASBESTOS FIBERS; GROWTH-FACTOR; MITOMYCIN-C; NUDE-MICE; EXPRESSION; P53 AB Pleural mesothelioma is an asbestos-related malignancy characterized by progressive local growth, late metastases, and median survivals between 8 and 18 months. It is only recently that the in vitro and in vivo characteristics of the malignancy have been investigated. These investigations have been aided by the development of cell lines from patients with the disease, as well as lines developed from asbestos-exposed animals. Nude mouse models constructed with subcutaneous, intraabdominal, or intrathoracic innoculation of cultured cell lines or fresh tumor have been used for evaluating response to innovative therapies. Karyotyping has been performed on a number of cell lines and multiple abnormalities involving many chromosomes have been identified. Aneuploidy is commonly seen, along with reported non-random patterns of chromosomal abberations. The role of tumor suppressor genes, including p53 is controversial. Multiple growth factors including PDGF are being investigated for a possible paracrine/autocrine loop, and PDGF receptors seem to be differentially expressed in mesothelioma cells compared to normal mesothelial cells. The role of cytokines in the pathophysiology of the disease, secreted either by the tumor cells themselves or by monocyte/macrophages in the local tumor environment, remains to be defined. (C) 1996 Wiley-Liss, Inc.* RP Pass, HI (reprint author), NCI,THORAC ONCOL SECT,SURG BRANCH,NIH,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 71 TC 1 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 142 EP 151 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300010 ER PT J AU Sullivan, FJ Carmichael, J Glatstein, E Mitchell, JB AF Sullivan, FJ Carmichael, J Glatstein, E Mitchell, JB TI Radiation biology of lung cancer SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE lung cancer; radiation sensitivity; oncogenes; dose rate; chemosensitivity ID HUMAN SMALL CELL; INVITRO PHOTODYNAMIC THERAPY; DOSE-RATE IRRADIATION; RAS ONCOGENE; MAMMALIAN-CELLS; PROTO-ONCOGENE; MYC ONCOGENE; H-RAS; IONIZING-RADIATION; P53 ONCOGENE AB The enormous problem that is lung cancer still defies satisfactory therapeutic strategy. This article summarizes some of the more important laboratory efforts directed at understanding the biology of this complex disease. The radiation sensitivities of established lung cancer cell lines are outlined. The effect of radiation dose rate and chemotherapy is explored. The emerging biology of oncogenetic alterations is explored as it relates to radiation sensitivity in general, and lung cancer in particular. Finally, novel therapeutic approaches including photodynamic therapy are introduced. (C) 1996 Wiley-Liss, Inc.* C1 NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20992. GEN HOSP,NOTTINGHAM HLTH AUTHOR,DEPT CLIN ONCOL,NOTTINGHAM NG1 6HA,ENGLAND. UNIV SW TEXAS,SIMMONS CANC CTR,DALLAS,TX. NR 68 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 152 EP 159 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300011 ER PT J AU Kratzke, RA Kramer, BS AF Kratzke, RA Kramer, BS TI Evaluation of in vitro chemosensitivity using human lung cancer cell lines SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE chemosensitivity; MTT; synergy; lung cancer; supraadditive ID HIGH-DOSE LEUCOVORIN; INVITRO DRUG-SENSITIVITY; NECK-CANCER; CYTO-TOXICITY; ADVANCED HEAD; MTT ASSAY; CHEMOTHERAPY; CISPLATIN; 5-FLUOROURACIL; FLUOROURACIL AB The use of well-characterized human lung cancer cell lines has allowed for new opportunities in preclinical and clinical drug evaluation. Development of semiautomated tests of in vitro cytotoxicity such as the MTT assay, which utilizes the formazan salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), has allowed for preclinical evaluation of novel chemotherapeutic agents and drug combinations. In addition, techniques such as this make possible the testing of sufficient data sets to allow determination of true biochemical drug synergy. Assessment of drug combinations which possess in vitro synergy or supraadditive effects can suggest chemotherapeutic regimens for further clinical testing. Using the MTT assay in conjunction with isobolographic analysis, it is possible to test commonly used regimens which are based on presumed or apparent in vivo drug synergy, such as the combination of etoposide and cis-platinum. This frequently prescribed combination was found to lack in vitro biochemical synergy when tested with human lung cancer cell lines, indicating that the observed clinical benefits of this drug combination may be due to factors in the tumor microenvironment, drug metabolism, or non-overlapping toxicities. Finally, although it remains to be determined if a significant role for in vitro drug testing will be found in direct clinical applications, preclinical drug evaluation during the drug development process using cultured tumor cell lines may ultimately allow for disease or patient specific therapies for testing. (C) 1996 Wiley-Liss, Inc.* C1 NCI,EARLY DETECT & COMMUNITY ONCOL PROGRAM,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20889. VET AFFAIRS MED CTR,DEPT MED,MINNEAPOLIS,MN. RP Kratzke, RA (reprint author), NCI,NAVY MED ONCOL BRANCH,DIV CANC TREATMENT,BETHESDA,MD 20889, USA. NR 31 TC 5 Z9 5 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 160 EP 164 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300012 ER PT J AU Dearing, MP EngleeMiller, MJ Kratzke, RA Kramer, BS Chu, E Weinstein, J Anderson, M Venzon, D Mulshine, JL Gazdar, AF AF Dearing, MP EngleeMiller, MJ Kratzke, RA Kramer, BS Chu, E Weinstein, J Anderson, M Venzon, D Mulshine, JL Gazdar, AF TI Dipyridamole mediated enhanced antiproliferative activity of 10-ethyl-10-deazaaminopterin (10-EDAM) against human lung cancer cell lines SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE 10-EDAM; dipyridamole; methotrexate; lung cancer ID 10-DEAZA-AMINOPTERIN SERIES; FOLATE ANALOGS; CYTO-TOXICITY; DOSE METHOTREXATE; CARCINOMA; 5-FLUOROURACIL; POTENTIATION; METABOLISM; MODULATION; ETOPOSIDE AB 10-ethyl-10-deazaaminopterin (10-EDAM) is a rationally designed derivative of the antifolate, methotrexate (MTX). In a number of tumor models these design features have resulted in an improved spectrum of antiproliferative activity as compared with the parent compound. Using an MTT growth assay, we compared in vitro antiproliferative activity of 10-EDAM with MTX in eight lung cancer cell lines. Growth was inhibited in all lines tested by clinically achievable concentrations of 10-EDAM (0.1-1,000 nM). 10-EDAM was more cytotoxic than MTX at the same concentrations in all eight lung cancer cell lines. In an effort to enhance the antiproliferative effect, we evaluated the addition of dipyridamole (DPM), an inhibitor of nucleoside transport, to 10-EDAM (0.1-10 mu m). DPM decreased the concentration of 10-EDAM required to cause 50% growth inhibition (IC50) in all eight cell lines tested. This suppression was statistically significant by 2-sided sign test (P = .0078). By contrast, the IC50 of MTX was decreased in only two of the eight cell lines when DPM was added (0.1-10 mu M). In defined thymidine depleted media, cell kill by the combination of 10-EDAM and DPM was no greater than 10-EDAM alone, consistent with the possibility that DPM exerts some of its effect by inhibition of extrinsic nucleoside salvage. In consideration of the published activity of 10-EDAM in lung cancer and the modest clinical toxicity of DPM based biochemical modulation, we conclude the current in vitro data provide justification for clinical evaluation of this combination in patients with lung cancer. (C) 1996 Wiley-Liss, Inc.* C1 NCI,NAVAL MED ONCOL BRANCH,DIV CANC TREATMENT,BETHESDA,MD 20889. NCI,EARLY DETECT & COMMUNITY ONCOL PROGRAM,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20889. NCI,MATH BIOL LAB,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20889. NCI,BIOSTAT & DATA MANAGEMENT SECT,DIV CANC TREATMENT,BETHESDA,MD 20889. RI Venzon, David/B-3078-2008 NR 33 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 165 EP 172 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300013 ER PT J AU Shaw, GL Gazdar, AF Phelps, R Steinberg, SM Linnoila, RI Johnson, BE Oie, HK Russell, EK Ghosh, BC Pass, HI Minna, JD Mulshine, JL Ihde, DC AF Shaw, GL Gazdar, AF Phelps, R Steinberg, SM Linnoila, RI Johnson, BE Oie, HK Russell, EK Ghosh, BC Pass, HI Minna, JD Mulshine, JL Ihde, DC TI Correlation of in vitro drug sensitivity testing results with response to chemotherapy and survival: Comparison of non-small cell lung cancer and small cell lung cancer SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE non-small cell lung cancer; small cell lung cancer; drug resistance; cell survival ID FREE DEFINED MEDIUM; CLINICAL SPECIMENS; ENDOCRINE TUMORS; GROWTH; LINES; CARCINOMA; INVITRO; IDENTIFICATION; ESTABLISHMENT; TRIAL AB Clinical protocols for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) were devised to prospectively select individualized chemotherapy based on in vitro drug sensitivity testing (DST) of cell lines derived from the patient's SCLC tumor cell lines or the patient's fresh NSCLC tumor. DST data derived from SCLC tumor cell lines were available for 33/115 (29%) patients. The DST-selected chemotherapy regimen was administered to 21 (18%) patients, or 64% of patients with DST. In SCLC, the DST-selected chemotherapy was administered either during weeks 13-24 following 12 weeks of etoposide/cisplatin, or at relapse after complete response to etoposide/cisplatin. Several parameters of in vitro drug sensitivity were significantly associated (two-sided P < 0.05) with clinical response to primary therapy and also with response to the DST-selected chemotherapy regimen, but were not associated with survival (P = 0.24). Five patients treated with their DST-seleaed chemotherapy attained a complete or partial response, compared to 5 of 68 who received an empiric regimen (P = 0.057). A total of 36/165 (22%) NSCLC patients had DST successfully completed. These results directed management for 21/96 (22%) patients who eventually received chemotherapy, or 58% of patients with DST. Response to chemotherapy for the patients treated prospectively with their DST-seleaed chemotherapy regimen (2/21; 9%) was not significantly different than the response rate for patients treated empirically with etoposide/cisplatin (10/69; 14%) in the absence of in vitro results to direct chemotherapy (P = 0.73). There was no difference in survival by treatment group for the NSCLC patients. The correlation between in vitro and clinical response was not significant for any individual drug or for all drugs considered together, illustrating the poor predictive value of in vitro testing with currently available chemotherapy in NSCLC. (C) 1996 Wiley-Liss, Inc. C1 UNIV TEXAS, SW MED CTR, SIMMONS COMPREHENS CANC CTR, DALLAS, TX 75235 USA. NCI, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, PULM DIS SECT, BETHESDA, MD 20889 USA. WASHINGTON UNIV, SCH MED, ST LOUIS, MO 63110 USA. RP Shaw, GL (reprint author), UNIV S FLORIDA, H LEE MOFFIT CANC CTR & RES INST, 12902 MAGNOLIA DR, TAMPA, FL 33612 USA. NR 34 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 173 EP 185 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300014 ER PT J AU Buchhagen, DL AF Buchhagen, DL TI Frequent involvement of chromosome 3p alterations in lung carcinogenesis: Allelotypes of 215 established cell lines at six chromosome 3p loci SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE lung cancer; chromosome 3p; allelotypes; DNA; heterozygosity ID HUMAN-BREAST CARCINOMA; SHORT ARM; DNA-SEQUENCE; HOMOZYGOUS DELETION; ALLELIC LOSS; REGION 3P21; CANCER; HETEROZYGOSITY; GENE; RECEPTOR AB We have determined the allelotypes of 215 established lung cancer cell lines by PCR analysis at six loci on the short arm of chromosome 3 (3p): D3S3 (3p12-p13), D3S30 (3p13), D3S2 (3p14-p21.1), D3S32 (3p21), D3F15S2 (3p21), and THRB (3p24). Eighty seven small cell lung cancer (SCLC), 93 non-small cell lung cancer (NSCLC), 6 extrapulmonary SCLC, 6 mesothelioma, and 23 normal B lymphocyte (BL) cell lines were analyzed. Low levels of heterozygosity at all six 3p loci were seen in both the SCLC and NSCLC cells. SCLC cell lines exhibited the lowest frequencies of heterozygosity at D3S3 (3%), D3S2 (3%), D3F15S2 (10%), and THRB (6%) when compared with frequencies of 8, 42, 48, and 34% at these same loci in the normal population. The lowest frequencies of heterozygosities among the NSCLC cell lines were seen at D3S3 (5%), DF15S2 (17%), and THRB (15%). Adenocarcinoma (Ad) was the only subtype of NSCLC that exhibited any heterozygosity (7%) at D3S3. In addition to D3S3, the lowest frequencies of heterozygosity were seen at D3F15S2 for Ad (9%), D3S2 for large cell carcinomas (8%), and THRB for adenosquamous (0%), bronchioloalveolar (0%), and large cell (8%) carcinomas. In summary, the 3p chromosome region near the D3S3 locus (3p12-p13) appears to be involved in all forms of lung cancer with additional involvement of regions close to the D3S2 (3p14-p21.1), D3F15S2 (3p21), and THRB (3p24) loci. (C) 1996 Wiley-Liss, Inc. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. RP Buchhagen, DL (reprint author), UNIFORMED SERV UNIV HLTH SCI,NCI,NMOB,NATL NAVAL MED CTR,BETHESDA,MD 20814, USA. NR 46 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 198 EP 209 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300016 ER PT J AU Johnson, BE Russell, E Simmons, AM Phelps, R Steinberg, SM Ihde, DC Gazdar, AF AF Johnson, BE Russell, E Simmons, AM Phelps, R Steinberg, SM Ihde, DC Gazdar, AF TI MYC family DNA amplification in 126 tumor cell lines from patients with small cell lung cancer SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE lung neoplasms; oncogenes; drug therapy; mortality; pathology ID C-MYC; CYTOGENETIC ABNORMALITIES; GENE AMPLIFICATION; N-MYC; EXPRESSION; CHEMOTHERAPY; CARCINOMA; ONCOGENE; PROTOONCOGENES; REARRANGEMENT AB We identified 126 tumor cell lines established from patients with small cell cancer at the NCI-Navy Medical Oncology Branch from 1977 through 1992. Extensive clinical information was available on 96 patients from whom these cell lines were established. These patients comprised approximately one fourth of the 407 patients treated on prospective therapeutic clinical trials during the same time period. The proportion of tumor cell lines established from previously untreated patients with both limited and extensive stage small cell lung cancer increased during the 16 years of the study (P = 0.008). MYC family DNA amplification was present in 16 of 44 (36%) tumor cell lines established from previously treated patients compared to 7 of 52 (11%) of tumor cell lines established from untreated patients (P = 0.009). MYC DNA amplification in tumor cell lines established from patients previously treated with chemotherapy continued to be associated with shortened survival (P = 0.001). The initiation of a policy to obtain tumor tissue for the purpose of selecting chemotherapeutic agents given to individual patients was associated with an increase in the proportion of patients from whom tumor cell lines could be established for both extensive and limited stage patients (P = 0.0001 and 0.05, respectively). (C) 1996 Wiley-Liss, Inc. C1 NCI, OFF DIRECTOR, BETHESDA, MD 20892 USA. NCI, BIOMARKERS & PREVENT RES BRANCH, BETHESDA, MD 20892 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, CLIN ONCOL PROGRAM, BETHESDA, MD 20892 USA. RP Johnson, BE (reprint author), NATL NAVAL MED CTR, NCI, NAVY MED ONCOL BRANCH, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NR 30 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 210 EP 217 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300017 ER PT J AU Sabichi, AL Birrer, MJ AF Sabichi, AL Birrer, MJ TI Regulation of nuclear oncogenes expressed in lung cancer cell lines SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE lung cancer; cell lines; nuclear oncogenes; myc genes; c-jun; c-fos; transcription factors ID FAMILY DNA AMPLIFICATION; MYC GENE FAMILY; C-MYC; PROTEIN; TRANSCRIPTION; BINDING; MAX; ONCOPROTEIN; ACTIVATION; TUMORS AB Lung cancer is a major cause of mortality in the United States and accounts for the majority of all cancer deaths in both men acid women, It is hoped that through broadening our understanding of the mechanisms involved in transformation of bronchial epithelial cells we will be able to improve methods of diagnosis and treatment of this disease, with the ultimate goal of reducing on lung cancer mortality. A knowledge of the molecular mechanisms involved in processes such as cell division and differentiation is paramount to this task, because it is known that aberrant responses to growth factors or cytokines found in the normal cellular milieu can lead to abnormal cell growth and/or transformation. Signals initiated at the cell membrane by tumor promoters, growth factors, or cytokines are transduced from the cell membrane to the nucleus and are, in part, mediated centrally by transcription factors encoded by nuclear protooncogenes. The transcription factor myc, jun, and fos have been characterized in both normal and transformed lung epithelial cells through detailed studies using cell lines. In this manuscript, we review what is known about the expression and regulation of these nuclear protooncogenes in normal and malignant epithelial cells of the lung, and their role in the development of lung cancer. (C) 1996 Wiley-Liss, Inc.* RP Sabichi, AL (reprint author), NCI,BIOMARKERS & PREVENT RES BRANCH,DIV CLIN SCI,9610 MED CTR DR,SUITE 300,ROCKVILLE,MD 20850, USA. NR 31 TC 0 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 218 EP 227 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300018 ER PT J AU Viallet, J Sausville, EA AF Viallet, J Sausville, EA TI Involvement of signal transduction pathways in lung cancer biology SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE transduction; biological signals; oncogenesis; lung cancer; bombesin ID BOMBESIN-INDUCED MITOGENESIS; SWISS 3T3 CELLS; CALCIUM MOBILIZATION; CHOLERA-TOXIN; CARCINOMA CELLS; DOWN-REGULATION; G-PROTEINS; RECEPTOR; KINASE; INHIBITION AB Pathways involved in the transduction of biological signals within cells overlap with those involved in oncogenesis. Previous studies have identified a number of discrete disturbances of some elements of these pathways in human lung cancer cells, by virtue of the overexpression or the mutation of certain key molecules. The sequence of biochemical events triggered by a mitogenic stimulus such as the exposure to bombesin-like peptides are being unravelled. The opportunity exists to identify additional changes involving regulatory proteins which may contribute to the regulation of these systems and which may function as suppressors of the malignant phenotype. Furthermore, the understanding of these pathways may identify targets for the pharmacological regulation of tumor cell response to mitogens which may be usable in the clinic. (C) 1996 Wiley-Liss, Inc. C1 HOP NOTRE DAME DE BON SECOURS,DEPT MED,MONTREAL,PQ H2L 4M1,CANADA. UNIV MONTREAL,MONTREAL,PQ H2L 4M1,CANADA. NCI,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,DCT,BETHESDA,MD 20892. RP Viallet, J (reprint author), HOP NOTRE DAME DE BON SECOURS,CTR ONCOL,1560 RUE SHERBROOKE E,MONTREAL,PQ H2L 4M1,CANADA. NR 53 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 228 EP 236 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300019 ER PT J AU Fathi, Z Way, JW Corjay, MH Viallet, J Sausville, EA Battey, JF AF Fathi, Z Way, JW Corjay, MH Viallet, J Sausville, EA Battey, JF TI Bombesin receptor structure and expression in human lung carcinoma cell lines SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE bombesin receptor; gastrin releasing peptide receptor; neuromedin B receptor; bombesin; autocrine growth ID GASTRIN-RELEASING PEPTIDE; SWISS 3T3 CELLS; ANTAGONIST RC-3095; MOLECULAR-CLONING; GROWTH-FACTORS; NEUROMEDIN-B; EPITHELIAL-CELLS; DNA-SYNTHESIS; CANCER CELLS; BREAST AB Mammalian bombesin-like peptides gastrin-releasing peptide (GRP) and neuromedin B (NMB) are regulatory neuropeptides involved in numerous physiologic processes, and have been implicated as autocrine and/or paracrine growth factors in human lung carcinoma. Three structurally and pharmacologically distinct bombesin receptor subtypes have been isolated and characterized: the gastrin releasing peptide receptor (GRP-R), the neuromedin B receptor (NMB-R), and bombesin receptor subtype-3 (BRS-3). The three receptors are structurally related, sharing about 50% amino acid identity. They are members of the G-protein coupled receptor superfamily with a seven predicted transmembrane segment topology characteristic of receptors in this family. The signal transduction pathway for GRP-R and NMB-R involves coupling to a pertussis-toxin insensitive G-protein, activation of phospholipase C (PLC), generation of inositol trisphosphate (IP3), release of intracellular calcium, and activation of protein kinase C. While all three bombesin receptors are activated by bombesin agonists, GRP-R, NMB-R, and BRS-3 have very different affinities for the mammalian bombesin-like peptides GRP and NMB, as well as bombesin receptor antagonists. The three bombesin receptor subtypes are expressed in an overlapping subset of human lung carcinoma cell lines. Any therapeutic strategy based on modulation of bombesin growth responses in human lung carcinoma would be well served to take into account the pharmacologic heterogeneity of the relevant receptors. (C) 1996 Wiley-Liss, Inc.* C1 MONTREAL GEN HOSP,DIV ONCOL,MONTREAL,PQ H3G 1A4,CANADA. RP Fathi, Z (reprint author), NCI,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,BETHESDA,MD 20892, USA. NR 42 TC 10 Z9 10 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 237 EP 246 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300020 ER PT J AU Moody, TW Zia, F Venugopal, R Fagarasan, M Oie, H Hu, V AF Moody, TW Zia, F Venugopal, R Fagarasan, M Oie, H Hu, V TI GRP receptors are present in non small cell lung cancer cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE GRP receptor; cytosolic calcium; growth; arachidonic acid; protein kinase C ID GASTRIN-RELEASING PEPTIDE; SWISS 3T3 CELLS; BOMBESIN-LIKE PEPTIDES; NEUROMEDIN-B; ANTAGONIST RC-3095; CYTOSOLIC CALCIUM; ANALOGS FUNCTION; CLONAL GROWTH; HIGH-AFFINITY; LINES AB Previously, GRP receptors were characterized in small cell lung cancer cells and here non-small cell lung cancer (NSCLC) cells were investigated: (I-125-Tyr(4)) bombesin (BN) or I-125-GRP bound with high affinity to NCI-H720 (lung carcinoid) and NCI-H1299 (large cell carcinoma) cells. Binding was specific, time dependent, and saturable. Specific (I-125-Tyr(4))BN binding to NCI-H1299 cells was inhibited with high affinity by GRP, BN, GRP(14-27), (D-Phe(6))BN(6-13)methyl ester, moderate affinity by NMB, and low affinity by GRP(1-16). BN (10 nM) transiently elevated cytosolic calcium in a dose dependent manner. BN caused translocation of protein kinase C from the cytosol to the membrane and the translocation caused by BN was reversed by (D-Phe(6))BN(6-13)methylester. BN stimulated arachidonic acid release and the increase caused by BN was reversed by (D-Phe(6))BN(6-13)methylester. Using a clonogenic assay, BN stimulated the growth of NCI-H720 cells, and the number of colonies was reduced using (D-Phe(6))BN(6-13)methylester. These data suggest that GRP receptors that are present in lung carcinoid and NSCLC cells may regulate proliferation. (C) 1996 Wiley-Liss, Inc.* C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT MICROBIOL,WASHINGTON,DC 20037. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. RP Moody, TW (reprint author), NCI,BPRP,9610 MED CTR DR,BLDG C,RM 300,ROCKVILLE,MD 20850, USA. OI Hu, Valerie/0000-0002-3357-0777 NR 32 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 247 EP 256 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300021 ER PT J AU Vos, MD Scott, FM Iwai, N Treston, AM AF Vos, MD Scott, FM Iwai, N Treston, AM TI Expression in human lung cancer cell lines of genes of prohormone processing and the neuroendocrine phenotype SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE small cell lung cancer; non-small cell lung cancer; peptidylglycine alpha-amidating monooxygenase; lung tumor cell lines ID ALPHA-AMIDATING MONOOXYGENASE; PEPTIDE; BOMBESIN; DECARBOXYLASE; BIOSYNTHESIS; ENDOCRINE; GROWTH; ENZYME; CDNA AB Lung tumor cells and cell lines, principally the histologically classified small cell lung cancer, are characterized by the expression of neuroendocrine (NE) features including AADC (aromatic amino acid decarboxylase, previously called DOPA decarboxylase) and the production of many peptide hormones. The general mechanisms by which most aspects of the NE phenotype affect the clinical behavior of lung tumor cells are unknown, but it is well recognized that peptide hormones can have systemic effects (paraneoplastic syndromes) and several have been shown to be autocrine growth factors for cancer cells. In order to determine the relationship between expression of different aspects of the NE phenotype in lung cancer cell lines, we have compared expression of a gene required for biosynthesis of some active peptide hormones (PAM, peptidylglycine a-amidating monooxygenase) to the gene for AADC in 32 lung cancer cell lines. Expression of these genes was quantified by both steady state Northern blot analysis and radiochemical enzymatic activity measurements. To ensure a range of expression of NE markers, non-small cell lung cancer (NSCLC) cell lines were chosen to include several which had previously been shown to express NE markers, and several small cell lung cancer (SCLC) cell lines with previous low levels of AADC were included. PAM enzyme activity and Northern blot analysis showed a two to three log variation in levels of expression in both the small cell and non-small cell lines. A smaller range was found for AADC expression. Using the highly sensitive PAM enzyme assays, all cell lines were found to express detectable PAM. PAM activities were secreted into the growth medium of all cell lines. There was no simple correlation apparent between AADC and PAM gene expression in the lung cancer cell lines. However, classic small cell lines demonstrated high levels of expression of both PAM and AADC genes, as did the carcinoid subset of the NSCLC lines. NSCLC lines expressed levels of PAM mRNA and enzyme activities equivalent to those of SCLC, but had infrequent expression of AADC (principally only carcinoid NSCLC expressed AADC). These data demonstrate that separate aspects of the NE phenotype can be differentially expressed in lung cancer histological sub-types. Expression of PAM enzymes in all sub-types of lung cancer suggests that peptide prohormone activation may be a common mechanism for autocrine growth stimulation even in non-NE NSCLC cell lines, or may reflect maintenance in cell lines of a common pathway of lung tumor promotion. (C) 1996 Wiley-Liss, Inc.* C1 NCI, BIOMARKERS & PREVENT RES BRANCH, ROCKVILLE, MD 20850 USA. NR 38 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 257 EP 268 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300022 ER PT J AU Zia, F Jacobs, S Kull, F Cuttitta, F Mulshine, JL Moody, TW AF Zia, F Jacobs, S Kull, F Cuttitta, F Mulshine, JL Moody, TW TI Monoclonal antibody alpha IR-3 inhibits non-small cell lung cancer growth in vitro and in vivo SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE IGF-I; non-small cell lung cancer; monoclonal antibodies; growth; receptors ID I IGF-I; BINDING-PROTEINS; INSULIN-RECEPTOR; PEPTIDE; LINES; INVITRO; TUMORS; ACID AB The ability of monoclonal antibody (mAb) alpha IR-3 to interact with non-small cell lung cancer (NSCLC) cells was investigated. MAb alpha IR-3 inhibited specific binding of I-125-IGF-I and I-125-alpha-IR-3 to a panel of 8 NSCLC cell lines with high affinity (IC50 = 200 and 50 ng/ml, respectively). I-125-alpha IR-3 bound with high affinity (Kd = 40 ng/ml) to a single class of sites (Bmax = 8,000/cell) using NCI-H838 cells. I-125-alpha IR-3 was internalized when exposed to NCI-H838 or H1299 cells at 37 degrees C but not 4 degrees C. alpha IR-3 immunoprecipitated major 90 and 130 kD proteins. IGF-I stimulated and alpha IR-3 inhibited the clonal growth of NCI-H1299 cells. alpha IR-3 slowed the growth of NCI-H157 and H838 xenografts in nude mice. In a biodistribution study I-125-alpha IR-3 was preferentially localized to the tumor as opposed to other organs. These data suggest that IGF-I may be a regulatory agent in NSCLC. (C) 1996 Wiley-Liss, Inc.* C1 NCI,BPRP,ROCKVILLE,MD 20850. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT MICROBIOL,WASHINGTON,DC 20037. BURROUGHS WELLCOME CO,DIV CELL BIOL,RES TRIANGLE PK,NC 27709. NR 22 TC 8 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 269 EP 275 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300023 ER PT J AU Weiner, RE Avis, I Neumann, RD Mulshine, JL AF Weiner, RE Avis, I Neumann, RD Mulshine, JL TI Transferrin dependence of Ga (NO3)(3) inhibition of growth in human-derived small cell lung cancer cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE Ga nitrate; transferrin; transferrin receptors; small cell lung cancer ID IRON-METABOLISM; RIBONUCLEOTIDE REDUCTASE; GALLIUM NITRATE; MONOCLONAL-ANTIBODY; RECEPTOR; INVITRO; GA-67; PROLIFERATION; MECHANISMS; INVIVO AB The effect of a combination of anti-transferrin receptor (TFR) antibody, 42/6, and Ga(NO3)(3) on cell growth was examined in small cell lung cancer (SCLC) cell lines: classic, NCI-H209, NCI-H345, NCI-H510; and variant, NCI-H82 and NCI-N417. The role of TFR and transferrin (TF) in Ga(NO3)(3) cellular uptake was also tested. Exogenous TF did not enhance the cytotoxicity of Ga. At > 3 mu g/mL, Ga(NO3)(3) inhibited growth in all cell lines in TF-supplemented or deficient media. At < 3 mu g/mL, Ga stimulated growth for all cells but this effect was eliminated by TF or 42/6. Classic SCLC lines required 3-4-fold less exogenous gallium than variant lines to reduce cell number by 50%. The mean Ga uptake (ng/10(6) cells) in H345 and H209 cell lines tvas 4-5-fold compared to H82 and N417 uptake (P < 0.001). 42/6 reduced exogenous TF-stimulated growth. Antibody plus Ga(NO3)(3) caused a slight further cell number decline in all cell lines in TF-supplemented or deficient media. These results suggest that the addition of 42/6 antibody treatment would not increase the effectiveness of Ga(NO3)(3) in patients. Both exogenous and endogenous TF and TFR play an important role in Ga uptake in these cells. (C) 1996 Wiley-Liss, Inc. C1 NIH,CTR CLIN,BETHESDA,MD 20892. NCI,INTERVENT SECT,BIOMARKERS & PREVENT BRNCH,ROCKVILLE,MD 20850. RP Weiner, RE (reprint author), UNIV CONNECTICUT,CTR HLTH,DEPT NUCL MED,263 FARMINGTON AVE,FARMINGTON,CT 06030, USA. NR 35 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1996 SU 24 BP 276 EP 287 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UV113 UT WOS:A1996UV11300024 ER PT J AU Danielpour, D AF Danielpour, D TI Induction of transforming growth factor-beta autocrine activity by all-trans-retinoic acid and 1 alpha,25-dihydroxyvitamin D-3 in NRP-152 rat prostatic epithelial cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PHENOL-CHLOROFORM EXTRACTION; SINGLE-STEP METHOD; VITAMIN-D; DIFFERENTIAL REGULATION; RNA ISOLATION; TGF-BETA; CANCER; EXPRESSION; FACTOR-BETA-1; KERATINOCYTES AB Retinoids and vitamin D analogues are known to inhibit the proliferation of a variety of cells in culture and prevent the formation of certain tumors in mammals. Although it is well established that these hormones control the transcription of many genes upon binding to and activating specific nuclear receptors, the mechanisms by which they prevent cancer are as yet poorly understood. In this study the role of the transforming growth factor-beta (TGF-beta) growth inhibitors, in promoting the biological activities of all-trans-retinoic acid (RA) and 1 a,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) was studied in NRP-152 cells, a nontumorigenic epithelial line derived from rat dorsal-lateral prostate. Inhibition of growth by nanomolar concentrations of RA was associated with an increase in both mRNA and protein for all three TGF-beta isoforms, with greater and much earlier increases for TGF-beta s 2 and 3 (5.5 h) than for TGF-beta 1 (24 h). A monoclonal antibody against TGF-beta and TGF-beta 1 latency associated peptide (LAP), both of which neutralize all three TGF-beta isoforms, each block the ability of RA to inhibit growth of NRP-152 cells by >95%. Neutralization of growth inhibition by isoform-specific antibodies suggested that all three TGF-beta s are involved in this effect. The ability of RA to upregulate fibronectin and thrombospondin expression in NRP-152 cells was also blocked by the monoclonal antibody. 1,25-(OH)(2)D-3, which also induced TGF-beta s 2 and 3 but not TGF-beta 1, and their respective mRNAs, also induced fibronectin and thrombospondin through induction of TGF-beta. Thus, autocrine production of TGF-beta s may be a significant part of the mechanisms by which RA and 1,25-(OH)(2)D-3 promote cellular differentiation. (C) 1996 Wiley-Liss, Inc. RP Danielpour, D (reprint author), NCI,CHEMOPREVENT LAB,BLDG 41,ROOM C629,BETHESDA,MD 20892, USA. NR 46 TC 93 Z9 95 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JAN PY 1996 VL 166 IS 1 BP 231 EP 239 DI 10.1002/(SICI)1097-4652(199601)166:1<231::AID-JCP24>3.0.CO;2-G PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA TM554 UT WOS:A1996TM55400024 PM 8557772 ER PT J AU Sadato, N Ibanez, V Deiber, MP Campbell, G Leonardo, M Hallett, M AF Sadato, N Ibanez, V Deiber, MP Campbell, G Leonardo, M Hallett, M TI Frequency-dependent changes of regional cerebral blood flow during finger movements SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain; cerebral blood flow; fingers; motor cortex; positron emission tomography; reference values ID POSITRON EMISSION TOMOGRAPHY; CONTRASTING NEURONAL-ACTIVITY; CORTICAL FIELD POTENTIALS; ANTERIOR CINGULATE CORTEX; PRECENTRAL MOTOR CORTEX; PET IMAGES; MONKEY; STIMULATION; RESPONSES; SUPPLEMENTARY AB To study the effect of the repetition rate of a simple movement on the distribution and magnitude of neuronal recruitment, we measured regional CBF (rCBF) in eight normal volunteers, using positron emission tomography and O-15-labeled water. An auditory-cued, repetitive flexion movement of the right index finger against the thumb was performed at very slow (0.25 and 0.5 Hz), slow (0.75 and 1 Hz), fast (2 and 2.5 Hz), and very fast (3 and 4 Hz) rates. The increase of rCBF during movement relative to the resting condition was calculated for each pair of movement conditions. Left primary sensorimotor cortex showed no significant activation at the very slow rates. There was a rapid rise of rCBF between the slow and the fast rates, but no further increase at the very fast rates. The right cerebellum showed similar changes. Changes in the left primary sensorimotor cortex and the cerebellum likely reflect the effect of the movement rate. The posterior supplementary motor area (SMA) showed its highest activation at the very slow rates but no significant activation at the very fast rates. Changes correlating with those in the SMA were found in the anterior cingulate gyrus, right prefrontal area, and right thalamus. The decreases in CBF may reflect a progressive change in performance from reactive to predictive. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. RI Deiber, Marie-Pierre/M-5949-2014 NR 46 TC 155 Z9 155 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 1996 VL 16 IS 1 BP 23 EP 33 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA TM214 UT WOS:A1996TM21400003 PM 8530552 ER PT J AU Suh, T Schutz, CG Johanson, CE AF Suh, T Schutz, CG Johanson, CE TI Family structure and initiating non-medical drug use among adolescents SO JOURNAL OF CHILD & ADOLESCENT SUBSTANCE ABUSE LA English DT Article ID SUBSTANCE USE; MENTAL-HEALTH; MARITAL DISRUPTION; FOLLOW-UP; CHILDREN; DIVORCE; ANTECEDENTS; CHILDHOOD; CONSEQUENCES; NEIGHBORHOOD AB Using data from the 1991 and 1992 National Household Survey on Drug Abuse, multiple logistic regression models were used to estimate the relative risk of initiating non-medical drug use by 12-17-year-old adolescents living in families without both biological parents present compared to those living with both biological parents. To hold constant unmeasured socio-environmental confounding factors, we employed an epidemiological strategy that involves post-stratification of adolescents into neighborhood risk sets. The results indicated that adolescents living in families without both parents were more likely to initiate non-medical drug use, but the-se associations varied by sex. These results help measure the impact of divorce/separation/death and/or remarriage of parents on adolescents and identify subgroups at higher risk for initiating non-medical drug use. C1 NIDA,INTRAMURAL RES PROGRAM,ETIOL BRANCH,LEXINGTON,KY 40583. RP Suh, T (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,624 N BROADWAY,BALTIMORE,MD 21205, USA. NR 58 TC 11 Z9 11 U1 4 U2 9 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 SN 1067-828X J9 J CHILD ADOLES SUBST JI J. Child Adolesc. Subst. Abus. PY 1996 VL 5 IS 3 BP 21 EP 36 PG 16 WC Substance Abuse SC Substance Abuse GA WM455 UT WOS:A1996WM45500002 ER PT J AU VelezYanguas, MC Kalebic, T Maggi, M Kappel, CC Letterio, J Uskokovic, M Helman, LJ AF VelezYanguas, MC Kalebic, T Maggi, M Kappel, CC Letterio, J Uskokovic, M Helman, LJ TI 1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531) modulation of insulin-like growth factor-binding protein-3 and induction of differentiation and growth arrest in a human osteosarcoma cell line SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CLONAL OSTEOBLASTIC CELLS; FETAL-RAT CALVARIAE; FACTOR-I; OSTEOCALCIN SYNTHESIS; COLLAGEN-SYNTHESIS; FACTOR IGF; BONE; 1-ALPHA,25-DIHYDROXYVITAMIN-D3; 1,25-DIHYDROXYVITAMIN-D3; SEQUENCE AB 1 alpha,25-Dihydroxycholecalciferol [1,25-(OH)(2)D-3] is a potent differentiating agent in a variety of tumor cell lines. However, the induction of severe hypercalcemia has limited its clinical use. Several analogs have been synthesized that retain the antiproliferative differentiating effects of 1,25(OH)(2)D-3, but do not have the calcitropic effect of the parent compound. One such analog, 1 alpha,25(OH)(2)-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), can induce differentiation in HL-60 cells and does not induce hypercalcemia in animal models. We, therefore, evaluated the effect of Ro24-5531 on a human osteosarcoma cell Line, MG-63. Compared with 1,25-(OH)(2)D-3, the analog Ro24-5531 is 10-100 times more potent as an inhibitor of MG-63 cell proliferation, as determined by [H-3]thymidine incorporation and/or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The inhibition in cell growth is accompanied by a decrease in the expression of p34cdc2 (>4-fold), a protein critically involved in cell cycle regulation. Ro24-5531 treatment of MG-63, at a concentration of 10(-8) mol/L, induced expression of the bone differentiation markers biglycan and osteocalcin, as determined by Northern analysis. These data suggest that Ro24-3531 treatment induces growth arrest coupled with differentiation. To begin to evaluate the mechanisms by which Ro24-5531 may exert an effect, we evaluated the effect of Ro24-5531 on components of the insulin-like growth factor I (IGF-II signaling pathway, an important regulator of normal bone growth and differentiation. The expression of IGF-binding protein (IGFBP), IGFBP-3 messenger ribonucleic acid, and protein levels are increased 20-fold after 72 h of treatment with Ro24-5531 and are associated with a marked increase in detectable binding of ligand to binding protein, as measured by RRA. These data suggest an association between Ro24-5531-induced growth arrest and increased expression of IGFBP-3. C1 NCI, MOLEC ONCOL SECT, PEDIAT BRANCH, BETHESDA, MD 20892 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. HOFFMANN LA ROCHE INC, NUTLEY, NJ 07110 USA. UNIV FLORENCE, DEPT CLIN PHYSIOPATHOL, FLORENCE, ITALY. NR 43 TC 21 Z9 21 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 1996 VL 81 IS 1 BP 93 EP 99 DI 10.1210/jc.81.1.93 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TP939 UT WOS:A1996TP93900016 PM 8550801 ER PT J AU Karl, M VonWichert, G Kempter, E Katz, DA Reincke, M Monig, H Ali, IU Stratakis, CA Oldfield, EH Chrousos, GP Schulte, HM AF Karl, M VonWichert, G Kempter, E Katz, DA Reincke, M Monig, H Ali, IU Stratakis, CA Oldfield, EH Chrousos, GP Schulte, HM TI Nelson's syndrome associated with a somatic frame shift mutation in the glucocorticoid receptor gene SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN PITUITARY-TUMORS; RESISTANCE; TRANSCRIPTION; CORTISOL; ADENOMAS; BINDING; COMPLEX; DISEASE; ORIGIN; SITE AB Nelson's syndrome is the appearance and/or progression of ACTH-secreting pituitary macroadenomas in patients who had previously undergone bilateral adrenalectomy for Cushing's disease. Extremely high plasma ACTH levels and aggressive neoplastic growth might be explained by the lack of appropriate glucocorticoid negative feedback due to defective glucocorticoid signal transduction. To study the glucocorticoid receptor (GR) gene in Nelson's syndrome, DNA was extracted from pituitary adenomas and leukocytes of four patients with this condition and amplified by PGR for direct sequence analysis. In one of the tumors, a heterozygous mutation, consisting of an insertion of a thymine between complementary DNA nucleotides 1188 and 1189, was found in exon 2. This frame-shift mutation led to premature termination at amino acid residue 366 of the wild-type coding sequence, excluding the expression of a functioning receptor protein from the defective allele. The mutation was not detected in the sequence of the GR gene in the patient's leukocyte DNA, indicating a somatic origin. By lowering the receptor number in tumorous cells, this defect might have caused local resistance to negative glucocorticoid feedback similar to that caused by the presence of a null allele in a kindred with the generalized glucocorticoid resistance syndrome. P53 protein accumulation, previously reported in 60% of corticotropinomas, could not be detected in any of the four pituitary tumors examined by immunohistochemistry. We suggest that a somatic GR defect might have played a pathophysiological role in the tumorigenesis of the corticotropinoma bearing this mutation. C1 NINCDS, OFF CLIN DIRECTOR, BETHESDA, MD 20892 USA. NINCDS, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. INST HORMONE & FERTIL RES, W-2000 HAMBURG, GERMANY. UNIV WURZBURG, DEPT MED, W-8700 WURZBURG, GERMANY. CHRISTIAN ALBRECHTS UNIV KIEL, DEPT GEN INTERNAL MED, KIEL, GERMANY. RP Karl, M (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,MSC 1862, 10 CTR DR, BETHESDA, MD 20892 USA. NR 35 TC 64 Z9 67 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 1996 VL 81 IS 1 BP 124 EP 129 DI 10.1210/jc.81.1.124 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TP939 UT WOS:A1996TP93900020 PM 8550738 ER PT J AU Andersson, S Geissler, WM Wu, L Davis, DL Grumbach, MM New, MJ Schwarz, HP Blethen, SL Mendonca, BB Bloise, W Witchel, SF Cutler, GB Griffin, JE Wilson, JD Russell, DW AF Andersson, S Geissler, WM Wu, L Davis, DL Grumbach, MM New, MJ Schwarz, HP Blethen, SL Mendonca, BB Bloise, W Witchel, SF Cutler, GB Griffin, JE Wilson, JD Russell, DW TI Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TESTICULAR 17-KETOSTEROID REDUCTASE; MALE PSEUDOHERMAPHRODITISM; GYNECOMASTIA; HYPOGONADISM; ANDROGENS; SECRETION; TESTES AB Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedi one to testosterone by one or more of the unaffected 17 beta-hydroxysteroid dehydrogenase isoenzymes. C1 UNIV TEXAS, SW MED CTR, DEPT MOLEC GENET, DALLAS, TX 75235 USA. MERCK & CO INC, MERCK SHARP & DOHME RES LABS, DEPT BIOCHEM, RAHWAY, NJ 07065 USA. UNIV CALIF SAN FRANCISCO, DEPT PEDIAT, SAN FRANCISCO, CA 94143 USA. CORNELL UNIV, NEW YORK HOSP, MED CTR, DEPT PEDIAT, NEW YORK, NY 10021 USA. UNIV MUNICH, DEPT PEDIAT, MUNICH, GERMANY. SUNY STONY BROOK, DEPT PEDIAT, STONY BROOK, NY 11794 USA. UNIV SAO PAULO, DEPT MED, BR-05508 SAO PAULO, BRAZIL. UNIV PITTSBURGH, DEPT PEDIAT, PITTSBURGH, PA 15260 USA. NICHHD, BETHESDA, MD 20892 USA. UNIV TEXAS, SW MED CTR, DEPT INTERNAL MED, DALLAS, TX 75235 USA. RI Mendonca, Berenice/C-2827-2012; OI Russell, David/0000-0002-0277-403X FU NCRR NIH HHS [M01-RR-01271]; NIDDK NIH HHS [DK-03892]; NIGMS NIH HHS [GM-43753] NR 29 TC 133 Z9 139 U1 2 U2 4 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 1996 VL 81 IS 1 BP 130 EP 136 DI 10.1210/jc.81.1.130 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TP939 UT WOS:A1996TP93900021 PM 8550739 ER PT J AU Gross, DJ Avishai, N Meiner, V Filon, D Zbar, B Abeliovich, D AF Gross, DJ Avishai, N Meiner, V Filon, D Zbar, B Abeliovich, D TI Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMOR-SUPPRESSOR GENE; DISEASE; IDENTIFICATION AB We report a three generation, 25 member kindred with familial pheochromocytoma. Seven subjects of generations I and II had pheochromocytoma, in five of the seven, the tumors were bilateral, and in two of the seven, the tumors were both adrenal and extraadrenal. One patient also had a carotid body chemodectoma, and one patient had a malignant adrenal tumor and abdominal paraganglioma. In the patient with the chemodectoma, a cerebellar hemangioblastoma became manifest 25 yr after his initial diagnosis with pheochromocytoma, leading only then to a clinical diagnosis of von Hippel-Lindau disease (VHL). A mutational analysis of the VHL gene revealed a novel nucleotide 709 G-->T transversion present in all affected subjects and in four presymptomatic children. In familial pheochromocytoma the diagnosis of VHL should be considered, even when the formal criteria for diagnosis of the syndrome are lacking. C1 HADASSAH UNIV HOSP, DEPT HUMAN GENET, IL-91120 JERUSALEM, ISRAEL. HADASSAH UNIV HOSP, DEPT HEMATOL, IL-91120 JERUSALEM, ISRAEL. HEBREW UNIV JERUSALEM, HADASSAH MED SCH, IL-91120 JERUSALEM, ISRAEL. NCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. RP Gross, DJ (reprint author), HADASSAH UNIV HOSP, DEPT ENDOCRINOL & METAB, POB 12000, IL-91120 JERUSALEM, ISRAEL. NR 16 TC 43 Z9 45 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 1996 VL 81 IS 1 BP 147 EP 149 DI 10.1210/jc.81.1.147 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TP939 UT WOS:A1996TP93900024 PM 8550742 ER PT J AU DeRijk, RH Petrides, J Deuster, P Gold, PW Sternberg, EM AF DeRijk, RH Petrides, J Deuster, P Gold, PW Sternberg, EM TI Changes in corticosteroid sensitivity of peripheral blood lymphocytes after strenuous exercise in humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NECROSIS-FACTOR-ALPHA; GLUCOCORTICOID RECEPTOR; INTERLEUKIN-2 RECEPTORS; MONONUCLEAR LEUKOCYTES; TREADMILL EXERCISE; WHOLE-BLOOD; RESPONSES; THERAPY; RELEASE; CYTOKINES AB Although plasma corticosteroid concentrations can be measured accurately, the biological effect on the target tissue is uncertain. The availability of an accurate measure of corticosteroid sensitivity would potentially clarify the putative roles of endogenous glucocorticoids in illnesses such as inflammatory disease and obesity and allow evaluation of an additional regulatory level of glucocorticoid action. To measure corticosteroid sensitivity, we developed an assay based on the inhibition by dexamethasone (Dex) of lipopolysaccharide (LPS)-induced Interleukin-6 (IL-6) production and release in whole unseparated blood in vitro. LPS induced a dose-dependent increase in IL-6 concentrations up to 34 +/- 6.6 ng/mL, reaching plateau levels after 8 h, whereas Dex dose dependently inhibited LPS-induced IL-6 production. Involvement of the glucocorticoid receptor in this response was supported by abrogation of Dex (10(-7) mol/L) inhibition of IL-6 production by the glucocorticoid receptor antagonist RU 38486. To determine whether corticosteroid sensitivity is a dynamic phenomenon, we subjected healthy males to a graded quantifiable exercise associated with increases in plasma ACTH and cortisol. Before exercise, 3 x 10(-8) mol/L Dex inhibited LPS-induced IL-6 production in vitro; after exercise, 3 x 10(-8) and 10(-7) mol/L Dex were unable to inhibit IL-6 production. We conclude that Dex suppression of LPS-induced IL-6 production is an effective means of determining corticosteroid sensitivity and that corticosteroid sensitivity in human subjects is a dynamic, rather than a static, phenomenon. C1 UNIFORMED SERV UNIV HLTH SCI, DEPT PHYSIOL, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT MIL & EMERGENCY MED, BETHESDA, MD 20892 USA. RP DeRijk, RH (reprint author), NIMH, CLIN NEUROENDOCRINOL BRANCH,BLDG 10,ROOM 3S231, 10 CTR DR, MSC 1284, BETHESDA, MD 20892 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 34 TC 71 Z9 72 U1 0 U2 3 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 1996 VL 81 IS 1 BP 228 EP 235 DI 10.1210/jc.81.1.228 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TP939 UT WOS:A1996TP93900037 PM 8550757 ER PT J AU Ishikawa, N Eguchi, K Ohmori, T Momotani, N Nagayama, Y Hosoya, T Oguchi, H Mimura, T Kimura, S Nagataki, S Ito, K AF Ishikawa, N Eguchi, K Ohmori, T Momotani, N Nagayama, Y Hosoya, T Oguchi, H Mimura, T Kimura, S Nagataki, S Ito, K TI Defective organification of iodide causing congenital goitrous hypothyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN THYROID PEROXIDASE; IMPROVED ASSAY-METHOD; MICROSOMAL ANTIGEN; IDENTIFICATION; SEQUENCE; GOITER; ACID; THYROTROPIN; EXPRESSION; CDNA AB A 26-yr-old Japanese woman with congenital goitrous hypo-thyroidism and sensorineural deafness underwent a thyroidectomy. Examination of the thyroid gland revealed characteristic features of multinodular goiter. The T-3 and T-4 content in thyroglobulin (Tg) were 0.03 and 0.02 mol/mol Tg, respectively. Iodide incorporation into Tg, using slices of the thyroid tissue, revealed that iodide organification of thyroid tissue from our patient was markedly lower than that of normal controls. Then, guaiacol and iodide oxidation activities of thyroid peroxidase (TPO) in our patient's thyroid tissue were lower than those of normal controls (guaiacol assay: 1.92 vs. 30.0 +/- 5.7 mGU/mg protein; iodide assay: 1.1 us. 6.6 +/- 2.8 mIU/mg protein). Lineweaver-Burk plot analysis of the oxidation rates of guaiacol and iodide indicated that this patient's TPO had a defect in the binding of guaiacol and iodide, but the coupling activity of the patient's TPO was not decreased compared with those of two normal thyroids. In this case and in control subjects, Nothern gel analysis of TPO messenger RNA from unstimulated and TSH-stimulated thyroid cells revealed a 3.2 kilobase species in the former and four distinct messenger RNA species of 4.0, 3.2, 2.1, and 1.7 kilobases in the latter. Western blot analysis of TPOs obtained from this patient and from control subjects identified the same 107 kDa protein, using antimicrosomal antibody-positive serum. We analyzed the coding sequence in the patient's TPO gene by using polymerase chain reaction technique. A single point mutation of G-->C at 1265 base pair was detected only in the TPO gene, but this point mutation does not alter the amino acid residue. It is possible that posttranslational modification such as abnormal glycosylation may occur in the TPO molecules. Furthermore, it is possible that there are differences in the tertiary structures of the TPO molecules between our patient and normal subjects. The above abnormalities of TPO molecules may play an important role in our patient's dyshormonogenesis. C1 CHIBA UNIV, FAC PHARMACEUT SCI, CHIBA 263, JAPAN. NAGASAKI UNIV, SCH MED, DEPT INTERNAL MED 1, NAGASAKI 852, JAPAN. NCI, MOLEC CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. RP Ishikawa, N (reprint author), ITO HOSP, SHIBUYA KU, 4-3-6 JINGUMAE, TOKYO 150, JAPAN. OI nagataki, shigenobu/0000-0002-9974-3554 NR 24 TC 7 Z9 8 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 1996 VL 81 IS 1 BP 376 EP 383 DI 10.1210/jc.81.1.376 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TP939 UT WOS:A1996TP93900059 PM 8550781 ER PT J AU Hill, JM McCune, SK Alvero, RJ Glazner, GW Henins, KA Stanziale, SF Keimowitz, JR Brenneman, DE AF Hill, JM McCune, SK Alvero, RJ Glazner, GW Henins, KA Stanziale, SF Keimowitz, JR Brenneman, DE TI Maternal vasoactive intestinal peptide and the regulation of embryonic growth in the rodent SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE embryo; growth and embryonic development; growth factor; vasoactive intestinal peptide; maternal-fetal exchange ID FETAL THYROID-FUNCTION; NEUROTROPHIC ACTION; SPINAL-CORD; RAT; SURVIVAL; VIP; RECEPTORS; MITOSIS; WEIGHT; ONSET AB Vasoactive intestinal peptide (VIP) has been shown to regulate early postimplantation growth in rodents through central nervous sq stem receptors, However, the source of VIP mediating these effects is unknown. Although VIP binding sites are present prenatally, VIP mRNA was not detected in the rat central nervous system before birth and was detected in the periphery only during the last third of pregnancy, In the present study, the embryonic day (E11) rat embryo/trophoblast was shown to have four times the VIP concentration of the E17 fetus and to have VIP receptors in the central nervous system. However, no VIP mRNA was detected in the Ell rat embryo or embryonic membranes by in situ hybridization or reverse transcriptase-PCR, RIA of rat maternal serum revealed a peak in VIP concentration at days E10-E12 of pregnancy, with VIP rising to levels 6-10-fold higher than during the final third of pregnancy, After intravenous administration of radiolabeled VIP to pregnant female mice, undegraded VIP was found in the E10 embryo, These results suggest that maternal tissues may provide neuroendocrine support for embryonic growth through a surge of VIP during early postimplantation development in the rodent. C1 JOHNS HOPKINS UNIV HOSP,DEPT PEDIAT,DIV NEONATOL,BALTIMORE,MD 21287. RP Hill, JM (reprint author), NICHHD,DEV NEUROBIOL LAB,SECT DEV & MOLEC PHARMACOL,BLDG 49,ROOM 5A38,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 40 TC 50 Z9 50 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 1 PY 1996 VL 97 IS 1 BP 202 EP 208 DI 10.1172/JCI118391 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TQ105 UT WOS:A1996TQ10500028 PM 8550835 ER PT J AU Brunetti, A Brunetti, L Foti, D Accili, D Goldfine, ID AF Brunetti, A Brunetti, L Foti, D Accili, D Goldfine, ID TI Human diabetes associated with defects in nuclear regulatory proteins for the insulin receptor gene SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE insulin receptor; insulin resistance; non-insulin-dependent diabetes mellitus; gene transcription; trans-acting factors ID ACANTHOSIS NIGRICANS; PROMOTER REGION; DNA-BINDING; RESISTANCE; TRANSCRIPTION; EXPRESSION; MUTATIONS; DIFFERENTIATION; IDENTIFICATION; SEQUENCE AB The control of gene transcription is mediated bq sequence-specific DNA-binding proteins (trans-acting factors) that bind to upstream regulatory elements (cis elements), We have previously identified two DNA-binding proteins that specifically interact with two unique AT-rich sequences of the 5' regulatory region of the insulin receptor gene which have in vivo promoter activity, Herein we have investigated the expression of these DNA-binding proteins in cells from two unrelated patients with insulin resistance and non-insulin-dependent diabetes mellitus. In these patients, the insulin receptor gene was normal. In EBV-transformed lymphoblasts from both patients, insulin receptor mRNA levels and insulin receptor expression were decreased. The expression of nuclear-binding proteins for the 5' regulatory region of the insulin receptor gene was markedly reduced, and this defect paralleled the decrease in insulin receptor protein expression. These studies indicate that DNA-binding proteins to the regulatory region of the insulin receptor gene are important for expression of the insulin receptor. Further, they suggest that in affected individuals, defects in the expression of these proteins may cause decreased insulin receptor expression and insulin resistance. C1 UNIV REGGIO CALABRIA,FAC MED & CHIRURG,CATTEDRA ENDOCRINOL,I-88100 CATANZARO,ITALY. UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,DEPT MED,DIV DIABET & ENDOCRINE RES,SAN FRANCISCO,CA 94120. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. OI Foti, Daniela/0000-0002-9536-5736 FU NIDDK NIH HHS [DK26667] NR 40 TC 19 Z9 20 U1 3 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 1 PY 1996 VL 97 IS 1 BP 258 EP 262 DI 10.1172/JCI118400 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TQ105 UT WOS:A1996TQ10500036 PM 8550844 ER PT J AU Moss, RB Scott, TA Goldrich, M Pitale, M Daniel, A Lebovics, R Walker, R Igarashi, Y Kaliner, MA AF Moss, RB Scott, TA Goldrich, M Pitale, M Daniel, A Lebovics, R Walker, R Igarashi, Y Kaliner, MA TI Nasal mucosal cells in human immunodeficiency virus type 1-seropositive patients with sinusitis SO JOURNAL OF CLINICAL LABORATORY ANALYSIS LA English DT Article DE AIDS; CD4 cells; mast cells; opportunistic infections; upper airway; tissue phenotyping ID INFECTION; HIV-1 AB Recently, sinusitis has been recognized as a frequent clinical problem in human immunodeficiency virus (HIV-1)-infected individuals. We hypothesized that quantitative defects in immune cells in the nasal mucosa of HIV-positive subjects might mirror those in the peripheral blood and explain a predisposition to sinus disease in this population. Nasal mucosa biopsies were obtained from three different groups of patients--HIV-1 seropositive with sinusitis, HIV-1 seronegative with sinusitis, and HIV-1 seronegative without sinusitis (normal volunteer)--and phenotyped for cluster of differentiation antigen (CD) markers. In this study, we found patients with HIV-1 and sinus disease to have significantly lower numbers of both CD3 and CD4 nasal mucosa lymphocytes than seronegative controls in the nasal mucosa (P<0.05, P<0.01, respectively). A correlation between nasal mucosal CD4 cells and peripheral-blood CD4 cells was noted (R = 0.67, P less than or equal to 0.01). No deficiency in the number of nasal mucosa T or TC type mast cells was noted for the HIV-1-positive sinusitis group. Further study is warranted to define more completely the pathophysiology and microbiology of, and therapy for, this important clinical problem. (C) 1996 Wiley-Liss, Inc. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,NIH,BETHESDA,MD 20892. NIDCD,BETHESDA,MD. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 13 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-8013 J9 J CLIN LAB ANAL JI J. Clin. Lab. Anal. PY 1996 VL 10 IS 6 BP 418 EP 422 DI 10.1002/(SICI)1098-2825(1996)10:6<418::AID-JCLA18>3.0.CO;2-# PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA VV830 UT WOS:A1996VV83000018 PM 8951613 ER PT J AU Smith, M Arthur, D Camitta, B Carroll, AJ Crist, W Gaynon, P Gelber, R Heerema, N Korn, EL Link, M Murphy, S Pui, CH Pullen, J Reaman, G Sallan, SE Sather, H Shuster, J Simon, R Trigg, M Tubergen, D Uckun, F Ungerleider, R AF Smith, M Arthur, D Camitta, B Carroll, AJ Crist, W Gaynon, P Gelber, R Heerema, N Korn, EL Link, M Murphy, S Pui, CH Pullen, J Reaman, G Sallan, SE Sather, H Shuster, J Simon, R Trigg, M Tubergen, D Uckun, F Ungerleider, R TI Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PEDIATRIC-ONCOLOGY-GROUP; UNFAVORABLE PRESENTING FEATURES; POOR-PROGNOSIS; CANCER-GROUP; LYMPHOMATOUS PRESENTATION; TREATMENT FAILURE; BLAST CELLS; CHILDHOOD; THERAPY; INTENSIFICATION AB Purpose: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCl) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (FOG), Dana-Farber Cancer Institute (DFCl), St Jude Children's Research Hospital (SJCRH), and the CTEP. Methods: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. Results: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, similar to 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/mu L. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, similar to 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treat ment (eg, day-14 bone marrow), immunophenotype, and CNS status. Conclusions: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research. C1 ST JUDE CHILDRENS RES HOSP, CHILDRENS CANC GRP, MEMPHIS, TN 38105 USA. ST JUDE CHILDRENS RES HOSP, PEDIAT ONCOL GRP, MEMPHIS, TN 38105 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. RP Smith, M (reprint author), NCI, CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH, PEDIAT SECT,ROOM 741, EXECUT PLAZA N, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA 13539, CA 29139, CA 30969] NR 42 TC 487 Z9 494 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1996 VL 14 IS 1 BP 18 EP 24 PG 7 WC Oncology SC Oncology GA TP687 UT WOS:A1996TP68700004 PM 8558195 ER PT J AU Tolcher, AW Cowan, KH Noone, MH Denicoff, AM Kohler, DR Goldspiel, BR Barnes, CS McCabe, M Gossard, MR Zujewski, J OShaughnessy, JA AF Tolcher, AW Cowan, KH Noone, MH Denicoff, AM Kohler, DR Goldspiel, BR Barnes, CS McCabe, M Gossard, MR Zujewski, J OShaughnessy, JA TI Phase I study of paclitaxel in combination with cyclophosphamide and granulocyte colony-stimulating factor in metastatic breast cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL-LINES; TAXOL; MESNA AB Purpose: In vitro data suggest that prolonged exposure to paclitaxel enhances breast cancer cytotoxicity. Our objective in this phase I study was to determine the tolerability of paclitaxel administered by 72-hour continuous intravenous (IV) infusion (CIVI) in combination with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) in the ambulatory setting to metastatic breast cancer patients. Patients and Methods: Paclitaxel was administered over 72 hours by CIVI and cyclophosphamide was given daily by IV bolus on days 1,2, and 3, followed by G-CSF every 21 days. The availability of ambulatory infusion pumps and paclitaxel-compatible tubing permitted outpatient administration. Results: Fifty-five patients with metastatic breast cancer who had been previously treated with a median of two prior chemotherapy regimens were entered onto the study. Dose-limiting toxicity of grade 4 neutropenia for longer than 5 days and grade 4 thrombocytopenia occurred in three of five patients treated with paclitaxel 160 mg/m(2) CIVI and cyclophosphamide 3,300 mg/m(2) followed by G-CSF. The maximum-tolerated dose (MTD) was paclitaxel 160 mg/m(2) CIVI and cyclophosphamide 2,700 mg/m(2) in divided doses with G-CSF. Nonhematologic toxicities were moderate and included diarrhea, mucositis, and arthalgias. Although hemorrhagic cystitis developed in six patients, recurrence was prevented with IV and oral mesna, which permitted continued outpatient delivery. One hundred seventy-four cycles were safely administered in the ambulatory setting using infusional pumps and tubing. Objective responses occurred in 23 (one complete and 22 partial) of 42 patients with bidimensionally measurable disease (55%; 95% confidence interval, 38% to 70%), with a response rate of 73% (11 of 15) seen at the highest dose levels. Conclusion: paclitaxel by 72-hour CIVI with daily cyclophosphamide followed by G-CSF can be administered safely in the ambulatory setting, has acceptable toxicity, and is an active regimen in the treatment of metastatic breast cancer. (C) 1996 by American Society of Clinical Oncology. C1 NCI,MED BRANCH,BIOSTAT SECT,BETHESDA,MD 20892. NCI,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NR 21 TC 29 Z9 29 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1996 VL 14 IS 1 BP 95 EP 102 PG 8 WC Oncology SC Oncology GA TP687 UT WOS:A1996TP68700014 PM 8558227 ER PT J AU Benichou, J Gail, MH Mulvihill, JJ AF Benichou, J Gail, MH Mulvihill, JJ TI Graphs to estimate an individualized risk of breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROBABILITIES AB Purpose: Clinicians who counsel women about their risk for developing breast cancer need a rapid method to estimate individualized risk (absolute risk), as well as the confidence limits around that point, The Breast Cancer Detection Demonstration Project (BCDDP) model (sometimes called the Gall model) assumes no genetic model and simultaneously incorporates five risk factors, but involves cumbersome calculations and interpolations. This report provides graphs to estimate the absolute risk of breast cancer from the BCDDP model. Patients and Methods: The BCDDP recruited 280,000 women from 1973 to 1980 who were monitored for 5 years, From this cohort, 2,852 white women developed breast cancer and 3,146 controls were selected, all with complete risk-factor information. The BCDDP model, previously developed from these data, was used to prepare graphs that relate a specific summary relative-risk estimate to the absolute risk of developing breast cancer over intervals of 10, 20, and 30 years. Results: Once a summary relative risk is calculated, the appropriate graph is chosen that shows the 10, 20-, or 90-year absolute risk of developing breast cancer. A separate graph gives the 95% confidence limits around the point estimate of absolute risk. Once a clinician rules out a single gene trait that predisposes to breast cancer and elicits information on age and four risk factors, the tables and figures permit an estimation of a woman's absolute risk of developing breast cancer in the next three decodes. Conclusion: These results are intended to be applied to women who undergo regular screening, They should be used only in a formal counseling program to maximize a woman's understanding of the estimates and the proper use of them. C1 UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA. RP Benichou, J (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EXECUT PLAZA N,ROOM 403,MSC 7368,BETHESDA,MD 20892, USA. NR 33 TC 51 Z9 52 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1996 VL 14 IS 1 BP 103 EP 110 PG 8 WC Oncology SC Oncology GA TP687 UT WOS:A1996TP68700015 PM 8558184 ER PT J AU Thall, PF Simon, RM Estey, EH AF Thall, PF Simon, RM Estey, EH TI New statistical strategy for monitoring safety and efficacy in single-arm clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; CYTOSINE-ARABINOSIDE; VINCRISTINE; COMBINATION AB Purpose: Efficacy and toxicity are both important outcomes in cancer clinical trials. Nonetheless, most statistical designs for phase II trials only provide rules for evaluating treatment efficacy, and moreover only allow early stopping after fixed cohorts of patients have been treated. We illustrate a new statistical design strategy for monitoring both adverse and efficacy outcomes on a patient-by-patient basis in phase II and other single-arm clinical trials. Design: The new strategy is used to design a phase II trial of the experimental regimen idarubicin plus cytarabine (ara-C) plus cyclosporine for treatment of patients with intermediate-prognosis acute myelogenous leukemia (AML). The design requires a maximum of 56 patients and provides continuous monitoring boundaries to terminate the trial if the toxicity rate is unacceptably high or the complete remission (CR) rate is unacceptably low compared with the rates of these events with the standard regimen of anthracycline plus ara-C. Results: The design has an 88% to 91% probability of stoping the trial early with ct median of 15 to 18 patients if the toxicity rate of the experimental regimen is .05 to .10 above that of the standard and there is no improvement in the CR rate, If there is a .15 improvement in the CR rate and the toxicity rate is no more than .05 above that of the standard, then there is at least an 83% probability that the trial will run to completion. Conclusion: The proposed monitoring strategy provides a flexible, practical means to continuously monitor both safety and efficacy in single-arm cancer clinical trials. The design strategy can be implemented easily using a freely available menu-driven computer program, and provides a scientifically sound alternative to the use of ad hoc safety monitoring rules. (C) 1996 by American Society of Clinical Oncology. C1 UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT HEMATOL,HOUSTON,TX 77030. NCI,DIV CANC TREATMENT,BIOMETR RES BRANCH,ROCKVILLE,MD. RP Thall, PF (reprint author), UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT BIOMATH,BOX 237,1515 HOLCOMBE BVD,HOUSTON,TX 77030, USA. NR 9 TC 71 Z9 71 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1996 VL 14 IS 1 BP 296 EP 303 PG 8 WC Oncology SC Oncology GA TP687 UT WOS:A1996TP68700040 PM 8558211 ER PT J AU Pickar, D AF Pickar, D TI New strategies for treating psychosis - Introduction SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material RP Pickar, D (reprint author), NIH,DEPT HLTH & HUMAN SERV,EXPT THERAPEUT BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1996 VL 57 SU 11 BP 3 EP 3 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VV133 UT WOS:A1996VV13300001 ER PT J AU Potter, WZ AF Potter, WZ TI Adrenoceptors and serotonin receptor function: Relevance to antidepressant mechanisms of action SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 2nd International Conference on New Directions in Affective Disorders CY SEP 03-08, 1995 CL JERUSALEM, ISRAEL ID CEREBROSPINAL-FLUID; RAT; RELEASE; NOREPINEPHRINE; MICRODIALYSIS; ACETYLCHOLINE; METABOLITES; ANTAGONISTS; MODULATION; IDAZOXAN AB Hypotheses of antidepressant action which that even norepinephrine (NE) uptake inhibitors ultimately work through potentiation of serotonergic function are critically reviewed. Preclinical electrophysiologic data can be interpreted as evidence for enhanced serotonin (5-HT) throughput as a common mechanism of action of all antidepressants. Biochemical data in rats (e.g., microdialysis) and humans (e.g., opposite effects of ECT on 5-HIAA in cerebrospinal fluid), however, suggest that more is involved than simply enhanced 5-HT function when NE uptake inhibition is combined with 5-HT uptake inhibition. The case, however, for noradrenergic effects on 5-HT function is quite strong either with regard to stimulation of alpha(1) receptors on 5-HT cell bodies or alpha(2) heteroreceptors on 5-HT nerve endings. Even the reported ability of pindolol to potentiate the antidepressant effects of 5-HT uptake inhibitors may prove to involve noradrenergic effects and not simply antagonism of 5-HT1A receptors as currently hypothesized. The biochemically specific drugs needed to directly test these concepts are not yet available. On the other hand, compounds which combine noradrenergic and serotonergic effects (e.g., alpha(2) antagonism and 5-HT2 antagonism) that go beyond those of the classic uptake inhibitors are emerging as agents to test the clinical potential of selective manipulation of these interacting neurotransmitter systems. RP Potter, WZ (reprint author), NIMH, CLIN PHARMACOL SECT, BLDG 10, ROOM 2D 46, BETHESDA, MD 20892 USA. NR 45 TC 21 Z9 21 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1996 VL 57 SU 4 BP 4 EP 8 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA UP161 UT WOS:A1996UP16100002 PM 8636064 ER PT J AU Frye, MA Altshuler, LL Szuba, MP Finch, NN Mintz, J AF Frye, MA Altshuler, LL Szuba, MP Finch, NN Mintz, J TI The relationship between antimanic agent for treatment of classic or dysphoric mania and length of hospital stay SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 1st International Bipolar Conference CY JUN 22-24, 1994 CL PITTSBURGH, PA ID AFFECTIVE-ILLNESS; BIPOLAR DISORDER; CARBAMAZEPINE; VALPROATE; LITHIUM; EFFICACY AB Background: This retrospective study was conducted to evaluate the relationship between the mood-stabilizing agents lithium, carbamazepine, and divalproex sodium and time course of drug response as measured by length of hospital stay. Method: Seventy-eight patients were evaluated. Discharge date and length of hospitalization were obtained by review of the dictated discharge summary by investigators who were blind to medication status. Drug choice, including blood levels, was then identified as well as any adjunctive treatment. Statistical evaluation (SAS software) of time to improvement was conducted using nonparametric survival models. possible confounding variables were assessed by parametric survival regression models and proportional hazards models. Results: The individual survival curves of four major antimanic treatment groups revealed a significant difference by the second week of hospitalization in the divalproex sodium and the lithium/carbamazepine combination groups as compared with the lithium or carbamazepine groups (chi(2) = 13.83, df = 3, p = .003). The mean +/- SD length of stay was approximately 40% shorter for the divalproex sodium (10.2 +/- 2.0 days) and the lithium/carbamazepine combination (11.7 +/- 2.1 days) groups compared with the lithium alone (17.6 +/- 1.0 days) and the carbamazepine alone (18.1 +/- 3.0 days) groups. Regression analysis of possible confounding variables including adjunctive treatment (benzodiazepines and neuroleptics), severity of illness (number of years ill and previous hospitalizations), and discharge date revealed no statistically significant effect. Conclusion: Shortcomings of our study include those inherent in the design of a nonrandomized, small naturalistic study and retrospective chart review. Our study does, however, suggest different drug response rates for the treatment of classic and dysphoric mania and warrants further controlled investigation. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,VET ADM MED CTR,LOS ANGELES,CA 90024. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. OLIVE VIEW UCLA MED CTR,DEPT PSYCHIAT,SEPULVEDA,CA. NR 29 TC 41 Z9 42 U1 2 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JAN PY 1996 VL 57 IS 1 BP 17 EP 21 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA TP980 UT WOS:A1996TP98000004 PM 8543542 ER PT J AU Manji, HK Chen, G Hsiao, JK Risby, ED Masana, MI Potter, WZ AF Manji, HK Chen, G Hsiao, JK Risby, ED Masana, MI Potter, WZ TI Regulation of signal transduction pathways by mood-stabilizing agents: Implications for the delayed onset of therapeutic efficacy SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Time Course of Improvement in Acute Mania and Rationale for Drug Selection CY MAR 22, 1996 CL DALLAS, TX ID PROTEIN-KINASE-C; MONOAMINE NEUROTRANSMITTER INTERACTIONS; CYCLIC ADENOSINE-MONOPHOSPHATE; ADENYLATE-CYCLASE ACTIVITY; BIPOLAR AFFECTIVE-DISORDER; CEREBRAL-CORTEX; PHORBOL ESTER; LITHIUM TREATMENT; DOWN-REGULATION; GTP-BINDING AB A series of investigations were performed to elucidate the mechanisms of action of lithium, valproate, and carbamazepine. We have found that lithium exerts major effects on G proteins, most likely via a posttranslational process stabilizing the inactive heterotrimeric (alpha beta gamma) form of the protein. We also find that chronic lithium and valproate exert major, very similar effects on the PKC signaling pathway, with both drugs decreasing the levels of membrane-associated PKC alpha and epsilon, and have similar effects on the DNA binding activity of the transcription factor, AP-1. By contrast, we find that carbamazepine exerts major, direct inhibitory effect at the level of adenylyl cyclases. Overall, the results suggest that signal transduction pathways are targets for the actions of mood-stabilizing agents; given their key roles in the amplification and integration of signals in the central nervous system, these findings have clear implications not only for research into the etiology/pathophysiology of manic-depressive illness, but also for the development of innovative treatment strategies. C1 WAYNE STATE UNIV,SCH MED,DEPT PSYCHIAT & BEHAV NEUROSCI,MOL PATHOPHYSIOL PROGRAM,DETROIT,MI 48201. NIMH,SCHIZOPHRENIA BRANCH,ROCKVILLE,MD 20857. EMORY UNIV,SCH MED,DEPT PSYCHIAT,ATLANTA,GA 30322. NORTHWESTERN UNIV,DEPT BIOL CHEM & MOL PHARMACOL,CHICAGO,IL 60611. LILLY RES LABS,INDIANAPOLIS,IN. RP Manji, HK (reprint author), WAYNE STATE UNIV,SCH MED,DEPT PSYCHIAT & BEHAV NEUROSCI,DETROIT,MI 48201, USA. RI Chen, Guang/A-2570-2017 NR 109 TC 58 Z9 61 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1996 VL 57 SU 13 BP 34 EP 48 PG 15 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VY378 UT WOS:A1996VY37800005 PM 8970503 ER PT J AU Sunderland, T AF Sunderland, T TI Treatment of the elderly suffering from psychosis and dementia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Roundtable Meeting on Antipsychotic Drug Therapy - Current Status CY MAR 03, 1995 CL NEW ORLEANS, LA SP Janssen Pharm Inc ID NONCOGNITIVE BEHAVIORAL DISTURBANCES; NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE; EXTRAPYRAMIDAL SIGNS; SENSITIVITY; HALOPERIDOL; LOXAPINE AB Studies with elderly demented subjects have suggested that overt hostility agitation, hallucinosis, and hyperactivity are the most likely symptom profiles to respond to neuroleptics, but the available research data do not point to any one clear choice of medications. Meanwhile, recent government regulations require specific diagnosis-related indications for the use of neuroleptics. Unfortunately, there is still a general shortage of double-blind, placebo-controlled studies with either typical or atypical neuroleptics. Clinical treatment with neuroleptics requires careful evaluation of all extrapyramidal and possible cognitive side effects, especially with drugs having high anticholinergic potency. The long-term risk-benefit ratio for the use of typical or atypical neuroleptics in elderly demented patients is also uncertain, so adequate consideration should be given to non-neuroleptic medications before initiating a long-term trial of neuroleptics. RP Sunderland, T (reprint author), NIMH,NIH,CTR CLIN,SECT GERIATR PSYCHIAT,LAB CLIN SCI,BLDG 10,ROOM 3D41,10 CTR DR MSC 1264,BETHESDA,MD 20892, USA. NR 30 TC 19 Z9 19 U1 2 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1996 VL 57 SU 9 BP 53 EP 56 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VK186 UT WOS:A1996VK18600009 PM 8823351 ER PT J AU Goldberg, TE Weinberger, DR AF Goldberg, TE Weinberger, DR TI Effects of neuroleptic medications on the cognition of patients with schizophrenia: A review of recent studies SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Roundtable Meeting on Antipsychotic Drug Therapy - Current Status CY MAR 03, 1995 CL NEW ORLEANS, LA SP Janssen Pharm Inc ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; PSYCHIATRIC-SYMPTOMS; CLOZAPINE; ATTENTION; PLACEBO AB In this review, we have examined the effects of neuroleptic medications on neurocognitive functions in articles published since 1990. Based on recent work and reviews of older studies, neuroleptics do not appear to have marked positive or negative effects on working memory or secondary memory. In contrast, neuroleptic medications appear to have a salutary effect on sustained vigilance or response readiness. The relationship or lack thereof between changes in cognition and changes in clinical state (produced by neuroleptics) is also discussed. RP Goldberg, TE (reprint author), NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NIH,WASHINGTON,DC 20032, USA. NR 23 TC 97 Z9 100 U1 3 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1996 VL 57 SU 9 BP 62 EP 65 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VK186 UT WOS:A1996VK18600011 PM 8823353 ER PT J AU Bachus, SE Kleinman, JE AF Bachus, SE Kleinman, JE TI The neuropathology of schizophrenia SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; D2 DOPAMINE-RECEPTORS; CEREBRAL BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; MEDIAL TEMPORAL-LOBE; DECREASED HIPPOCAMPAL EXPRESSION; GLUTAMIC-ACID DECARBOXYLASE; NEUROLEPTIC-NAIVE PATIENTS; INCREASED BRAIN DOPAMINE; H-3 RACLOPRIDE BINDING AB Neuropharmacologic discoveries have driven much of the research on neural substrates of schizophrenia since the advent of neuroleptic drugs, which appear to share blockade of dopamine receptors as their common denominator. Yet, despite concerted efforts to identify the source of putative dopaminergic hyperactivity in the brain in schizophrenia, definitive evidence for the ''dopamine hypothesis of schizophrenia'' remains elusive. More recently, a ''neural systems'' approach, focusing on the limbic system, has yielded substantial convergent evidence, from bath in vivo imaging and postmortem morphological, biochemical, and molecular biological methods, implicating limbic cortex in the neuropathology underlying schizophrenia. Moreover, these limbic cortical regions modulate dopaminergic function in the striatum and nucleus accumbens, via glutamatergic projections. Increasingly, focus is shifting to a role for glutamatergic dysfunction in schizophrenia, opening the possibility that drugs that act upon glutamate function, either directly or indirectly via co-modulators of glutamate transmission, could potentially be developed as adjunctive or primary novel pharmacotherapeutic strategies. C1 ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. NR 240 TC 39 Z9 39 U1 7 U2 10 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 1996 VL 57 SU 11 BP 72 EP 83 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VV133 UT WOS:A1996VV13300011 PM 8941174 ER PT J AU Heinz, A Knable, MB Weinberger, DR AF Heinz, A Knable, MB Weinberger, DR TI Dopamine D-2 receptor imaging and neuroleptic drug response SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on New Strategies for Treating Psychosis CY JAN 12, 1996 CL COCONUT GROVE, FL ID POSITRON EMISSION TOMOGRAPHY; NAIVE SCHIZOPHRENIC-PATIENTS; ATYPICAL NEUROLEPTICS; CLINICAL-RESPONSE; BASAL GANGLIA; HUMAN BRAIN; OCCUPANCY; CLOZAPINE; BLOCKADE; PET AB Studies with positron emission tomography and single photon emission computed tomography have yielded important findings concerning the relationship between dopamine D-2 receptor occupancy and neuroleptic dose, plasma neuroleptic levels. and clinical response. For ''typical'' neuroleptics, therapeutic response is associated with occupancy levels as lour as 60%-70%, which can be achieved at lower doses than are routinely used. For these drugs, extrapyramidal side effects increase, and therapeutic response remains unchanged with higher occupancy levels. Although the mechanisms responsible for the improved clinical efficacy and tolerability of atypical neuroleptics are still poorly understood, antipsychotic efficacy has been observed at lower D-2 receptor occupancy rates than with typical neuroleptics. It is unclear whether the lower incidence of extrapyramidal side effects observed with the atypical neuroleptic clozapine can be attributed to its lower D-2 occupancy, its relatively specific effects on the ventral striatum, or its nondopaminergic effects. There are a number of additional unresolved issues, including the high interindividual variation in scan outcome measurements, possible effects of concomitant medication, possible effects of endogenous dopamine, and assumptions in various strategies used to model receptor densities and occupancy rates. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,DIV INTRAMURAL RES PROGRAMS,WASHINGTON,DC 20032. NR 42 TC 20 Z9 20 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1996 VL 57 SU 11 BP 84 EP 88 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA VV133 UT WOS:A1996VV13300012 PM 8941175 ER PT J AU Davatzikos, C Vaillant, M Resnick, SM Prince, JL Letovsky, S Bryan, RN AF Davatzikos, C Vaillant, M Resnick, SM Prince, JL Letovsky, S Bryan, RN TI A computerized approach for morphological analysis of the corpus callosum SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE image analysis; corpus callosum; image registration; brain, morphology; magnetic resonance imagery ID SEX-RELATED DIFFERENCES; MAGNETIC-RESONANCE; MORPHOMETRIC ANALYSIS; DIMORPHISM; HANDEDNESS; ISTHMUS; HAND AB Objective: A new technique for analyzing the morphology of the corpus callosum is presented, and it is applied to a group of elderly subjects. Materials and Methods: The proposed approach normalizes subject data into the Talairach space using an elastic deformation transformation. The properties of this transformation are used as a quantitative description of the callosal shape with respect to the Talairach atlas, which is treated as a standard. In particular, a deformation function measures the enlargement/shrinkage associated with this elastic deformation. Intersubject comparisons are made by comparing deformation functions. Results: This technique was applied to eight male and eight female subjects. Based on the average deformation functions of each group, the posterior region of the female corpus callosum was found to be larger than its corresponding region in the males. The average callosal shape of each group was also found, demonstrating visually the callosal shape differences between the two groups in this sample. Conclusion: The proposed methodology utilizes the full resolution of the data, rather than relying on global descriptions such as area measurements. The application of this methodology to an elderly group indicated sex-related differences in the callosal shape and size. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL & RADIOL SCI,NEUROIMAGING LAB,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,DEPT ELECT & COMP ENGN,IMAGE ANAL & COMMUN LAB,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,LAB PERSON & COGNIT,BALTIMORE,MD 21224. RI Prince, Jerry/A-3281-2010; Bryan, R. Nick/P-1661-2014 OI Prince, Jerry/0000-0002-6553-0876; FU NIA NIH HHS [1-AG-3-2124, 1R01 AG13743-01] NR 29 TC 226 Z9 226 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 1996 VL 20 IS 1 BP 88 EP 97 DI 10.1097/00004728-199601000-00017 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TT590 UT WOS:A1996TT59000017 PM 8576488 ER PT J AU Horowitz, AM Nourjah, PA AF Horowitz, AM Nourjah, PA TI Patterns of screening for oral cancers among US adults. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 9 EP 9 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100009 ER PT J AU Tomar, SL Winn, DM Kleinman, DV AF Tomar, SL Winn, DM Kleinman, DV TI Smokeless tobacco-associated oral lesions in US school children. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 CDC,OFF SMOKING & HLTH,ATLANTA,GA. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 13 EP 13 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100011 ER PT J AU Simmons, D Gu, TT Leach, R Krebsbach, PH MacDougall, M AF Simmons, D Gu, TT Leach, R Krebsbach, PH MacDougall, M TI Identification and temporal expression of cDNA for murine ameloblastin. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SCH DENT,SAN ANTONIO,TX 78284. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 73 EP 73 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100073 ER PT J AU Drury, TF Snowden, CB AF Drury, TF Snowden, CB TI The oral health of poor adults in metropolitan America. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NIDR,LANHAM,MD. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 135 EP 135 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100132 ER PT J AU KayserJones, J Bird, W Redford, M AF KayserJones, J Bird, W Redford, M TI An ethnographic study of oral health problems and eating behavior. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 136 EP 136 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100136 ER PT J AU Brunelle, JA Marcus, SE Winn, DM Brown, LJ AF Brunelle, JA Marcus, SE Winn, DM Brown, LJ TI Trends in oral health status of the elderly, 1971-1991. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 192 EP 192 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100192 ER PT J AU Ruhl, S Sandberg, AL Cisar, JO AF Ruhl, S Sandberg, AL Cisar, JO TI Salivary proteins and glycoproteins recognized by Actinomyces and streptococcal adhesions SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV REGENSBURG,DEPT OPERAT DENT,W-8400 REGENSBURG,GERMANY. UNIV REGENSBURG,DEPT PERIODONTOL,W-8400 REGENSBURG,GERMANY. NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 208 EP 208 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100208 ER PT J AU Leiendecker, TM York, AK Poindexter, FR Chisick, MC Kaste, LM White, BA Zion, G AF Leiendecker, TM York, AK Poindexter, FR Chisick, MC Kaste, LM White, BA Zion, G TI Tobacco use among Navy and Marine Corps recruits. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NDRI DET,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 519 EP 519 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100516 ER PT J AU Eidelman, N Fowler, BO Joshi, R Levy, RJ AF Eidelman, N Fowler, BO Joshi, R Levy, RJ TI Characterization of calcified deposits on polyurethane implants by FTIR microscopy. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 ADAHF PRC,GAITHERSBURG,MD. NIST,NIDR,GAITHERSBURG,MD 20899. UNIV MICHIGAN,SCH MED,ANN ARBOR,MI. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 574 EP 574 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100575 ER PT J AU Shugars, DC McNeely, TB Eisenberg, SP Wahl, SM AF Shugars, DC McNeely, TB Eisenberg, SP Wahl, SM TI Secretory leukocyte protease inhibitor targets an early event in HIV infection. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV N CAROLINA,SCH DENT,CHAPEL HILL,NC. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 775 EP 775 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100772 ER PT J AU Yamada, KM Robey, PG BirkedalHansen, H AF Yamada, KM Robey, PG BirkedalHansen, H TI Symposium: Cell interactions in development. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 826 EP 826 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100829 ER PT J AU Mackert, JR Russell, CM EvansWilliams, AL AF Mackert, JR Russell, CM EvansWilliams, AL TI Evidence of a critical leucite particle radius for microcracking in dental porcelains. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NIST,AMER DENT ASSOC HLTH FDN,GAITHERSBURG,MD 20899. MED COLL GEORGIA,AUGUSTA,GA 30912. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 866 EP 866 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100869 ER PT J AU Code, JE Antonucci, JM Schumacher, GE Bennett, PS AF Code, JE Antonucci, JM Schumacher, GE Bennett, PS TI Silane-modified dentin bonding systems. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD. NIST,AMER DENT ASSOC HLTH FDN,GAITHERSBURG,MD 20899. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 870 EP 870 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100871 ER PT J AU Furman, LJ Adesanya, MR Streckfus, CF Brown, LJ AF Furman, LJ Adesanya, MR Streckfus, CF Brown, LJ TI Effects of aging on periodontal status: The Baltimore longitudinal study of aging. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. UNIV MISSISSIPPI,MED CTR,JACKSON,MS 39216. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 899 EP 899 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100898 ER PT J AU Dionne, RA AF Dionne, RA TI Review of preemptive analgesia for dental pain. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,NAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 950 EP 950 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100951 ER PT J AU Dionne, RA Gordon, SM Dubner, R AF Dionne, RA Gordon, SM Dubner, R TI Relationship of prostaglandin E(2) to acute pain and analgesia. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,NAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 954 EP 954 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100957 ER PT J AU Selwitz, RH Leverett, DH Billings, RJ AF Selwitz, RH Leverett, DH Billings, RJ TI Relation between dental fluorosis and use of dietary fluoride supplements. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 EASTMAN DENT CTR,ROCHESTER,NY. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 999 EP 999 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80100996 ER PT J AU Skrtic, D Antonucci, JM Eanes, ED AF Skrtic, D Antonucci, JM Eanes, ED TI Modified amorphous calcium phosphate fillers for bioactive composite applications. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NIST,GAITHERSBURG,MD 20899. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1017 EP 1017 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101017 ER PT J AU Shklar, G Schwartz, JL AF Shklar, G Schwartz, JL TI Retinoid and carotenoid action differs on tumor angiogenesis SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,SCH DENT MED,CAMBRIDGE,MA 02138. NIDR,DIV MOLEC EPIDEMIOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1062 EP 1062 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101063 ER PT J AU Ho, D Litz, M Letterio, J Roberts, AB DSouza, RN AF Ho, D Litz, M Letterio, J Roberts, AB DSouza, RN TI Histopathological analyses of dentition in adult TGF beta 1-deficient mice. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DENT BRANCH,HOUSTON,TX 77225. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1160 EP 1160 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101160 ER PT J AU Guckes, AD Roberts, MW Chiou, F Mccarthy, GR AF Guckes, AD Roberts, MW Chiou, F Mccarthy, GR TI Permanent teeth present in individuals with ectodermal dysplasia and severe hypodontia. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1200 EP 1200 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101200 ER PT J AU Kaste, LM Baird, DD HertzPicciotto, I Rowland, AS Savitz, DA Shy, C Weintraub, JA Winn, DM AF Kaste, LM Baird, DD HertzPicciotto, I Rowland, AS Savitz, DA Shy, C Weintraub, JA Winn, DM TI Spontaneous abortion and mixing amalgam among female dentists. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC 27515. NIEHS,RES TRIANGLE PK,NC 27709. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1340 EP 1340 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101342 ER PT J AU Marcus, SE Winn, DM Brown, LJ AF Marcus, SE Winn, DM Brown, LJ TI Tobacco use and tooth loss in the United States, 1988-91 SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1347 EP 1347 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101346 ER PT J AU Stack, KM Selwitz, R Drury, TF AF Stack, KM Selwitz, R Drury, TF TI Socioeconomic variations in sealant presence among US children ages 5-17 SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1359 EP 1359 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101356 ER PT J AU NowjackRaymer, RE Drury, TF Selwitz, RH AF NowjackRaymer, RE Drury, TF Selwitz, RH TI Association of sealant presence and untreated decay in US children SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1360 EP 1360 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101360 ER PT J AU Watson, EL AF Watson, EL TI Risk factor assessment in a clinical setting to identify osteoporotic patients. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1365 EP 1365 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101363 ER PT J AU Whittaker, CJ Kolenbrander, PE AF Whittaker, CJ Kolenbrander, PE TI Analysis of an intrageneric coaggregation-relevant adhesin gene from Streptococcus gordonii DL1 SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1523 EP 1523 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101521 ER PT J AU Andersen, RN Kolenbrander, PE AF Andersen, RN Kolenbrander, PE TI Binding of Helicobacter pylori with oral fusobacteria SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1526 EP 1526 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101526 ER PT J AU Adesanya, MR Baur, U Brunelle, JA Kaste, LM Zion, G Streckfus, CF Brown, LJ AF Adesanya, MR Baur, U Brunelle, JA Kaste, LM Zion, G Streckfus, CF Brown, LJ TI Periodontal measurement issues in a low disease population SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. UNIV MISSISSIPPI,MED CTR,JACKSON,MS 39216. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1532 EP 1532 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101533 ER PT J AU Ren, K Dubner, R AF Ren, K Dubner, R TI An inflammation hyperalgesia model for the study of orofacial pain SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UMAB,SCH DENT,DEPT ORAL & CRANIOFACIAL BIOL SCI,BALTIMORE,MD. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1595 EP 1595 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101592 ER PT J AU Yamane, A Takahashi, K Vo, H ZeichnerDavid, M Slavkin, H AF Yamane, A Takahashi, K Vo, H ZeichnerDavid, M Slavkin, H TI Effect of TGF alpha on Myf5 expression during tongue myogenesis SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 TSURUMI UNIV,YOKOHAMA,KANAGAWA,JAPAN. UNIV SO CALIF,CTR CRANIOFACIAL MOLEC BIOL,LOS ANGELES,CA 90033. NIDR,BETHESDA,MD 20892. RI Zeichner-David, Margarita/A-6567-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1728 EP 1728 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101726 ER PT J AU Hoffman, MP Letterio, JJ Lee, SK Kleinman, HK AF Hoffman, MP Letterio, JJ Lee, SK Kleinman, HK TI TGF-beta 2 and -beta 3 isoforms predominate in acinar differentiation and in submandibular gland development SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1865 EP 1865 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101863 ER PT J AU He, X Kiujpers, GAJ Goping, G Pollard, HB Baum, BJ AF He, X Kiujpers, GAJ Goping, G Pollard, HB Baum, BJ TI An immortalized rat submandibular epithelial cell exhibits surface polarity and acinar-like characteristics SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NIDDK,NIH,LCBG,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1870 EP 1870 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101869 ER PT J AU Meehan, S Ambudkar, IS AF Meehan, S Ambudkar, IS TI Characterization of agonist-induced Ca2+ responses in a rat submandibular gland epithelial cell line SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,CLIN INVEST & PATIENT CARE BRANCH,SECRETORY PHYSIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1871 EP 1871 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101866 ER PT J AU Atchison, KA Gift, HC AF Atchison, KA Gift, HC TI Application of qualitative research in oral health SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH DENT,LOS ANGELES,CA 90024. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1875 EP 1875 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101872 ER PT J AU ZeichnerDavid, M Arzate, H Gonzales, E Bringas, P Vo, H Slavkin, HC AF ZeichnerDavid, M Arzate, H Gonzales, E Bringas, P Vo, H Slavkin, HC TI Characterization of Hertwig's epithelial root sheath (HERS) cells maintained in cell culture SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV SO CALIF, SCH DENT, CTR CRANIOFACIAL MOLEC BIOL, LOS ANGELES, CA 90089 USA. Univ Nacl Autonoma Mexico, MEXICO CITY, DF, MEXICO. NIDR, BETHESDA, MD 20892 USA. RI Zeichner-David, Margarita/A-6567-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1944 EP 1944 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101942 ER PT J AU Kobayashi, S Ando, Y Yagi, M Saski, T Kobayashi, H Horowitz, AM AF Kobayashi, S Ando, Y Yagi, M Saski, T Kobayashi, H Horowitz, AM TI DMFT trends in Niigata of 12-year-olds with and without use of fluoride mouthrinse SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIIGATA UNIV,NIIGATA 95021,JAPAN. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1965 EP 1965 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101961 ER PT J AU Jung, JY Paik, DI Moon, HS Kim, JB Horowitz, AM AF Jung, JY Paik, DI Moon, HS Kim, JB Horowitz, AM TI Knowledge, opinions and practices about caries prevention among Korean oral hygienists SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 SEOUL NATL UNIV,COLL DENT,SEOUL,SOUTH KOREA. NIDR,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1968 EP 1968 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101966 ER PT J AU Albandar, JM Brown, LJ Kingman, A AF Albandar, JM Brown, LJ Kingman, A TI Association between calculus and gingival inflammation and the progression of early onset periodontitis over 6 years SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1978 EP 1978 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101979 ER PT J AU Ehrich, D Lundgren, J Dionne, R Nicoll, B Hutter, J AF Ehrich, D Lundgren, J Dionne, R Nicoll, B Hutter, J TI Comparison of oral triazolam, diazepam, and placebo as outpatient premedication for endodontic patients SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 USN,SCH DENT,BETHESDA,MD. NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 1996 EP 1996 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80101996 ER PT J AU Redford, M Drury, TF AF Redford, M Drury, TF TI Self-reported use of, and perceived problems with, complete dentures SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2006 EP 2006 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102005 ER PT J AU Gannot, G Chen, ZJ Fox, PC AF Gannot, G Chen, ZJ Fox, PC TI Fas-mediated effects on a human salivary cell line SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,LOM,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2025 EP 2025 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102023 ER PT J AU Grisius, MM Bermudez, D Fox, PC AF Grisius, MM Bermudez, D Fox, PC TI Salivary TGF-beta 1 in primary Sjogren's syndrome SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2026 EP 2026 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102027 ER PT J AU Sun, D EmmertBuck, MR Fox, PC AF Sun, D EmmertBuck, MR Fox, PC TI Localization of cytokine production in human labial salivary glands SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NCI,NIH,PATHOL LAB,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2027 EP 2027 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102024 ER PT J AU Wu, AJ Lafrenie, R Park, C Apinhasmit, W Chen, AJ Yamada, KM BirkedalHansen, H StetlerStevenson, WG Baum, BJ AF Wu, AJ Lafrenie, R Park, C Apinhasmit, W Chen, AJ Yamada, KM BirkedalHansen, H StetlerStevenson, WG Baum, BJ TI Production of matrix metalloproteinases in Sjogren's syndrome SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2028 EP 2028 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102028 ER PT J AU Kingman, A Duggan, DM Martin, LR Reinhardt, JW AF Kingman, A Duggan, DM Martin, LR Reinhardt, JW TI Quality control procedures used in the NIDR amalgam study. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2255 EP 2255 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102249 ER PT J AU Gu, X Schwartz, JL Wright, L Diehl, SR AF Gu, X Schwartz, JL Wright, L Diehl, SR TI HPV infection in benign and malignant oral lesions. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIH,NIDR,MOLEC EPIDEMIOL & DIS INDICATORS BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2525 EP 2525 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102520 ER PT J AU Schumcher, GE Antonucci, JM Nikaido, T Code, JE AF Schumcher, GE Antonucci, JM Nikaido, T Code, JE TI Molar efficiency of N-phenyliminodiacetic acid in dentin bonding. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2641 EP 2641 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102638 ER PT J AU Satomura, K Ibaraki, K Kuznetsov, SA Rowe, D Young, MF Robey, PG AF Satomura, K Ibaraki, K Kuznetsov, SA Rowe, D Young, MF Robey, PG TI Protein tyrosine kinase expression in human bone marrow stromal fibroblasts. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BONE RES BRANCH,BETHESDA,MD. 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 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2666 EP 2666 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102666 ER PT J AU Brown, LJ Albandar, JM Brunelle, JA Loe, H AF Brown, LJ Albandar, JM Brunelle, JA Loe, H TI A 6-year study on the progression of early onset periodontitis. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2691 EP 2691 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102687 ER PT J AU Tessler, SJ Turner, RJ AF Tessler, SJ Turner, RJ TI The xerostomic effect of selected antihypertensive, antihistaminic, antidepressant and antimanic drugs is not due to downregulation of salivary Na+-K+Cl- cotransporter activity SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2856 EP 2856 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102853 ER PT J AU OConnell, AC Ambudkar, IS AF OConnell, AC Ambudkar, IS TI The functional integrity of irradiated salivary gland cells. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,CIPCB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 2862 EP 2862 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80102860 ER PT J AU Ried, KI Dionne, RA Denucci, DJ Dubner, R AF Ried, KI Dionne, RA Denucci, DJ Dubner, R TI Effect of TMJ anesthesia on muscle pain pressure thresholds. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UNIV KENTUCKY,LEXINGTON,KY 40506. NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 3327 EP 3327 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80103320 ER PT J AU Denucci, DJ Dionne, RA Graham, B Smoller, B Brodski, J Dubner, R AF Denucci, DJ Dionne, RA Graham, B Smoller, B Brodski, J Dubner, R TI Relationship of sleep disorders to the pathophysiology of chronic orofacial palm. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PY 1996 VL 75 SI SI BP 3328 EP 3328 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TT801 UT WOS:A1996TT80103324 ER PT J AU Rapoport, SI AF Rapoport, SI TI Modulation of blood-brain barrier permeability SO JOURNAL OF DRUG TARGETING LA English DT Editorial Material ID RAT-BRAIN; TUMOR BARRIER; INTRACAROTID INFUSION; CEREBRAL ENDOTHELIUM; HYPEROSMOTIC ARABINOSE; TIGHT JUNCTIONS; TISSUE-CULTURE; IN-VITRO; DISRUPTION; CHEMOTHERAPY AB Genetic and other defects leading to brain changes in Down syndrome, Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, Gaucher disease, hypertension and other disorders are rapidly being identified. If brain access were possible, new candidates for gene replacement therapy, antisense oligonucleotides, immune proteins or growth factors might be used for heating these diseases (Lowenstein et al., 1994; Wielbo et al., 1995). Further, a number of drugs, peptides, antibodies and biological response modifiers have proven valuable in inhibiting malignant, infectious and other pathological processes in vitro, but are unlikely to be employed clinically because of their limited access to brain. RP Rapoport, SI (reprint author), NIA,NIH,NEUROSCI LAB,BLDG 10,RM 6C103,BETHESDA,MD 20892, USA. NR 101 TC 35 Z9 35 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 1061-186X J9 J DRUG TARGET JI J. Drug Target. PY 1996 VL 3 IS 6 BP 417 EP 425 DI 10.3109/10611869609015962 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VC790 UT WOS:A1996VC79000002 PM 8863135 ER PT J AU Burklow, TR Moak, JP Bailey, JJ AF Burklow, TR Moak, JP Bailey, JJ TI Normal saline modulation of autonomic responses during tilt table testing SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 21st Annual ISCE Conference on Research and Technology Transfer in Computerized Electrocardiology CY APR 20-25, 1996 CL CHANDLER, AZ SP ISCE C1 NIH,BETHESDA,MD 20892. RP Burklow, TR (reprint author), CHILDRENS NATL MED CTR,WASHINGTON,DC 20010, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 1996 VL 29 SU S BP 97 EP 97 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WC574 UT WOS:A1996WC57400036 ER PT J AU Norman, JE Levy, D AF Norman, JE Levy, D TI Adjustment of ECG left ventricular hypertrophy criteria for body mass index and age improves classification accuracy: The effects of hypertension and obesity SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT 21st Annual ISCE Conference on Research and Technology Transfer in Computerized Electrocardiology CY APR 20-25, 1996 CL CHANDLER, AZ SP ISCE DE ECG criteria; left ventricular hypertrophy; body mass index; age; Cornell voltage-duration product ID ELECTROCARDIOGRAPHIC DIAGNOSIS; VALIDATION AB Population-based data from the Framingham Heart Study have served as the basis for adjusting electrocardiographic (EGG) criteria for echocardiographically determined left ventricular hypertrophy (LVH) for two determinants of their sensitivity: body mass index and age. Estimated regression equations that predict echo-derived left ventricular mass from an ECG LVH voltage criterion, body mass index, and age, for 1,468 men and 1,883 women, provide a simple and effective means of adjusting that criterion for these variables. The authors evaluated five different ECG LVH criteria, comparing the performances of their original and adjusted versions within this database. All adjusted criteria significantly outperformed their unadjusted counterparts. Of these five criteria, the Cornell voltage duration product, (RAVL + SV3). QRS interval, exhibited the greatest sensitivity at all levels of specificity for both sexes (39 and 51% sensitivity at 95% specificity in men and women, respectively). Its performance was further evaluated with separate adjustment algorithms developed for lean versus obese and normotensive versus hypertensive men and women. Age and body mass index adjustment produced significant improvements for both lean and obese women and for obese men. A marginal gain in sensitivity was found in lean normotensive men. Within the relatively small subgroup of lean hypertensive men, no improvement was observed. These results suggest that among Caucasian adults, the Cornell voltage duration product adjusted for body mass index and age offers significant improvement for the detection of echocardiographically determined LVH in all but lean men; within the latter group, it loses no sensitivity in comparison with the original criterion. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. RP Norman, JE (reprint author), NHLBI,ROOM 8148,2 ROCKLEDGE CTR,6701 ROCKLEDGE DR,MSC 7,BETHESDA,MD 20892, USA. NR 16 TC 14 Z9 15 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PY 1996 VL 29 SU S BP 241 EP 247 DI 10.1016/S0022-0736(96)80070-7 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WC574 UT WOS:A1996WC57400070 PM 9238407 ER PT J AU Kelsall, BL Strober, W AF Kelsall, BL Strober, W TI Distinct populations of dendritic cells are present in the subepithelial dome and T cell regions of the murine Peyer's patch SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MONOCLONAL-ANTIBODY; LANGERHANS CELLS; MOUSE SPLEEN; ANTIGEN; IDENTIFICATION; INTESTINE; MICE; MACROPHAGES; EXPRESSION; ORGANS AB Despite the fact that the Peyer's patch (PP) is the primary site for antigen uptake in the intestine, the cellular basis of antigen handling after transport into the PP is poorly understood. We performed immunohistology of murine PPs using the dendritic cell (DC)-reactive monoclonal antibodies N418, NLDC-145, M342, and 2A1, as well as antibodies to other T cell, B cell, and macrophage markers. N418(+), 2A1(+), NLDC-145(-), M342(-) cells form a dense layer of cells in the subepithelial dome (SED), just beneath the follicle epithelium, and are scattered throughout the follicle, sparing the germinal center. In contrast, N418(+), 2A1(+), NLDC-145(+), and M342(+) DCs are present in the interfollicular T cell regions (IFR). CD3(+) and CD4(+), but no CD8(+) T cells were present in the SED and the follicle, including the germinal center, while CD3(+), CD4(+), and CD8(+) T cells were present in the IFR. B cells and macrophages were poorly represented in the SED as no B220(+) cells, only few Mac-1(lo) cells, and no F4/80(+) cells were present at this site. In contrast, Mac-1(hi) cells were found in the IFR and lamina propria of intestinal villi, while F4/80(+) cells were found only in the latter. In further phenotypic studies, we analyzed surface molecules of PP and spleen DCs by flow cytometry and found that these cells had similar fluorescence profiles when stained with N418, NLDC-145, and 33D1 DC-reactive antibodies, and antibodies to the costimulatory molecules B7-1 (1G10) and B7-2 (GL1). In contrast, PP DCs expressed 5-10-fold higher levels of major major histocompatibility complex class II antigens (IE(k)) than spleen DCs. Finally, in functional studies, we demonstrated that both PP and spleen DCs process soluble protein antigens during overnight culture and induce similar levels of proliferation in CD3(+) T cells, and CD4(+)/Mel 14(hi) T cells from T receptor transgenic mice. The in vivo relevance of such presentation was shown by the fact that PP DCs isolated from Balb/c mice after being fed ovalbumin stimulated proliferation in ovalbumin T cell receptor T cells. Taken together, our data suggest that DCs in the SED of the PP are uniquely positioned for the processing of antigens passed into the PP from the overlying M cell, and that PP DCs are effective at processing and presenting oral antigens to naive T cells. RP Kelsall, BL (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BLDG 10,ROOM 11N238,9000 ROCKVILLE PIKE,BETHESDA,MD 20814, USA. NR 36 TC 284 Z9 293 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 1 PY 1996 VL 183 IS 1 BP 237 EP 247 DI 10.1084/jem.183.1.237 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA TP365 UT WOS:A1996TP36500025 PM 8551227 ER PT J AU Wilkinson, DJ Mansoura, MK Watson, PY Smit, LS Collins, FS Dawson, DC AF Wilkinson, DJ Mansoura, MK Watson, PY Smit, LS Collins, FS Dawson, DC TI CFTR: The nucleotide binding folds regulate the accessibility and stability of the activated state SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS GENE; CHLORIDE CHANNEL; ESCHERICHIA-COLI; ATP-BINDING; ADENYLATE KINASE; STRUCTURAL MODEL; FUNCTIONAL ROLES; XENOPUS OOCYTES; BETA-SUBUNIT AB The functional roles of the two nucleotide binding folds, NBF1 and NBF2, in the activation of the cystic fibrosis transmembrane conductance regulator (CFTR) were investigated by measuring the rates of activation and deactivation of CFTR Cl- conductance in Xenopus oocytes. Activation of wild-type CFTR in response to application of forskolin and 3-isobutyl-1-methylxanthine (IBMX) was described by a single exponential. Deactivation after washout of the cocktail consisted of two phases: an initial slow phase, described by a latency, and an exponential decline, Rate analysis of CFTR variants bearing analogous mutations in NBF1 and NBF2 permitted us to characterize amino acid substitutions according to their effects on the accessibility and stability of the active state. Access to the active state was very sensitive to substitutions for the invariant glycine (G551) in NBF1, where mutations to alanine (A), serine (S), or aspartic acid (D) reduced the apparent on rate by more than tenfold. The analogous substitutions in NBF2 (G1349) also reduced the on rate, by twofold to 10-fold, but substantially destabilized the active state as well, as judged by increased deactivation rates. In the putative ATP-binding pocket of either NBF, substitution of alanine, glutamine (Q), or arginine (R) for the invariant lysine (K464 or K1250) reduced the on rate similarly, by two- to fourfold. III contrast, these analogous substitutions produced opposite effects on the deactivation rate. NBF1 mutations destabilized the active state, whereas the analogous substitutions in NBF2 stabilized the active state such that activation was prolonged compared with that seen with wild-type CFTR. Substitution of asparagine (N) for a highly conserved aspartic acid (D572) in the ATP-binding pocket of NBF1 dramatically slowed the on rate and destabilized the active state. In contrast, the analogous substitution in NBF2 (D1370N) did not appreciably affect the on rate and markedly stabilized the active state. These results are consistent with a hypothesis for CFTR activation that invokes the binding and hydrolysis of ATP at NBF1 as a crucial step in activation, while at NBF2, ATP binding enhances access to the active state, but the rate of ATP hydrolysis controls the duration of the active state. The relatively slow time courses for activation and deactivation suggest that slow processes modulate ATP-dependent gating. C1 UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,BIOENGN PROGRAM,ANN ARBOR,MI 48109. HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK29786, DK45880] NR 56 TC 47 Z9 47 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JAN PY 1996 VL 107 IS 1 BP 103 EP 119 DI 10.1085/jgp.107.1.103 PG 17 WC Physiology SC Physiology GA TQ794 UT WOS:A1996TQ79400008 PM 8741733 ER PT J AU Shakil, AO DiBisceglie, AM Hoofnagle, JH AF Shakil, AO DiBisceglie, AM Hoofnagle, JH TI Seizures during alpha interferon therapy SO JOURNAL OF HEPATOLOGY LA English DT Article DE alpha interferon; chronic hepatitis; seizures; side-effects ID CHRONIC HEPATITIS-B; CONTROLLED TRIAL; ALFA THERAPY AB Background/Aims: Alpha interferon is now used widely in the therapy of chronic viral hepatitis. The common side effects of interferon are well known; the uncommon side effects are less well defined. We have evaluated the incidence and characteristics of seizures that occurred during alpha interferon therapy. Methods: A retrospective chart review was done on 311 patients with chronic hepatitis treated with alpha interferon between 1983 and 1994 at the National Institutes of Health. Results: Four of 311 patients (1.3%) developed grand mal seizures while on therapy with alpha interferon. Three patients had chronic hepatitis B (two had an accompanying glomerulonephritis) and one chronic delta hepatitis. Interferon had been given in doses of 5-10 million units each day or three times weekly for 2-14 months before the onset of seizures. No other obvious cause for seizures was identified. Seizures resolved once interferon was stopped, and did not recur even without chronic anticonvulsant therapy. Conclusions: Alpha interferon in the doses used to treat chronic viral hepatitis caused seizures in approximately 1% of patients. C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD 20892. NR 18 TC 43 Z9 45 U1 0 U2 2 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. PD JAN PY 1996 VL 24 IS 1 BP 48 EP 51 DI 10.1016/S0168-8278(96)80185-1 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TT384 UT WOS:A1996TT38400008 PM 8834024 ER PT J AU Saldise, L Martinez, A Montuenga, LM Treston, A Springall, DR Polak, JM Vazquez, JJ AF Saldise, L Martinez, A Montuenga, LM Treston, A Springall, DR Polak, JM Vazquez, JJ TI Distribution of peptidyl-glycine alpha-amidating mono-oxygenase (PAM) enzymes in normal human lung and in lung epithelial tumors SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE human lung; lung tumors; amidation; PAM; PHM; PAL ID GASTRIN-RELEASING PEPTIDE; MONOOXYGENASE PAM; PROCESSING ENZYME; NERVOUS-SYSTEM; CELLS; EXPRESSION; ENDOTHELIN; BOMBESIN; GROWTH; SECRETION AB C-terminal alpha-amidation is a post-translational modification necessary for the biological activity of many regulatory peptides produced in the respiratory tract. This modification is a two-step process catalyzed by two separate enzyme activities, both derived from the peptidyl-glycine alpha-amidating mono-oxygenase (PAM) precursor. The distribution of these two enzymes, peptidyl-glycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), was studied in the normal lung and in lung tumors using immunocytochemical methods and in sim hybridization. In normal lung the enzymes were located in some cells of the airway epithelium and glands, the endothelium of blood vessels, some chondrocytes of the bronchial cartilage, the alveolar macrophages, smooth muscle ails, neurons of the intrinsic ganglia, and in myelinated nerves, A total of 24 lung tumors of seven different histological types were studied, All cases contained PAM-immunoreactive cells with various patterns of distribution. All immunoreactive cells were positive for the PHM antiserum but only some of them for the PAL antiserum. The distribution of PAM co-localizes with some other previously described amidated peptides, suggesting that amidation is an important physiological process taking place in the normal and malignant human lung tissue. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,DCPC,ROCKVILLE,MD 20850. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 58 TC 27 Z9 27 U1 1 U2 4 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JAN PY 1996 VL 44 IS 1 BP 3 EP 12 PG 10 WC Cell Biology SC Cell Biology GA TM845 UT WOS:A1996TM84500002 PM 8543779 ER PT J AU Lederer, JA Liou, JS Kim, SM Rice, N Lichtman, AH AF Lederer, JA Liou, JS Kim, SM Rice, N Lichtman, AH TI Regulation of NF-kappa B activation in T helper 1 and T helper 2 cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; TH2 CLONES; ALPHA; MECHANISM; PROTEINS; RECEPTOR; ENCODES; BCL-3; PHOSPHORYLATION; INTERLEUKIN-2 AB In most cell types, NF-kappa B is activated by release from a cytoplasmic inhibitor protein, I kappa B, followed by its translocation to the nucleus where it binds to the regulatory regions of many genes, including the IL-2 gene in T lymphocytes. We have previously shown by electrophoretic mobility shift assays that nuclear extracts prepared from activated, non-IL-2-producing Th2 cell clones contain significantly less p65(RelA)-p50 NF-kappa B complexes than nuclear extracts from IL-2-producing Th1 and Th0 clones. We show here that Th1 and Th2 cells have similar levels of cytoplasmic p65(RelA) and p50, but TCR stimulation fails to induce the nuclear translocation of p65(RelA) in Th2 cells. Nuclear translocation of p65(RelA) can be induced by IL-1 stimulation of Th2 cells, indicating that a basic mechanism of NF-kappa B activation common to many cells is intact in Th2 cells. We demonstrate that IL-1 and TNF induce rapid nuclear translocation of p65(RelA) in T cell clones, whereas TCR-induced NF-kappa B activation in Th1 cells is delayed and may be longer in duration. This suggests that the TCR pathway of NF-kappa B activation is different from the cytokine pathway. Furthermore, we show that Th1 and Th2 cells express different levels and/or different forms of I kappa B alpha, and that cytokines, but not TCR stimuli, significantly modulate detectable levels of cytoplasmic I kappa B alpha. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV IMMUNOL RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NHLBI NIH HHS [HL07627] NR 35 TC 55 Z9 56 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1996 VL 156 IS 1 BP 56 EP 63 PG 8 WC Immunology SC Immunology GA TM171 UT WOS:A1996TM17100010 PM 8598494 ER PT J AU Chen, PW Wang, M Bronte, V Zhai, YF Rosenberg, SA Restifo, NP AF Chen, PW Wang, M Bronte, V Zhai, YF Rosenberg, SA Restifo, NP TI Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumor-associated antigen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEDIATED GENE-TRANSFER; INFILTRATING LYMPHOCYTES; CYSTIC-FIBROSIS; GLYCOPROTEIN-B; VIRUS; IDENTIFICATION; VACCINES; DISEASE; INVIVO; CELLS AB Recombinant adenovirus (rAd), deleted of critical genes that enable viral replication and replaced with genes encoding heterologous proteins, has been shown to be a safe and effective vector in gene therapy studies. To evaluate a potential role for rAd as an immunogen, we used two different replication-defective type 2 rAds encoding the model Ag, beta-galactosidase (beta-gal). To determine whether rAd elicited the kind of immune responses therapeutic in an anti-tumor setting, the beta-gal-expressing adenocarcinoma, CT26.CL25, was used, Splenocytes from BALB/c mice immunized with 1 x 10(7) infectious units (iu) of rAd demonstrated anti-beta-gal activity after in vitro culture with the relevant L(d) beta-gal peptide. Adoptive transfer of these same splenocytes produced dramatic regression of established pulmonary metastases. However, when tumor-bearing mice were treated with 1 x 10(7) iu of rAd, no reduction in established disease was observed even when rAd was given with exogenous IL-2. To increase the viral dose delivered to each animal, we used an E1/E4-deleted rAd that could be grown to much higher titers. Significant reduction occurred when 10-fold more rAd (1 x 10(8) iu) was administered. Exogenous IL-2 administration with 1 x 10(8) iu of rAd resulted in augmentation of this anti-tumor effect. These findings demonstrate that when using a nonreplicating virus, the viral dose is directly related to the immune response generated. These data constitute the first reported use of rAd in the treatment of an established experimental cancer and may have implications for the treatment of human cancer. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20814. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 48 TC 105 Z9 106 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1996 VL 156 IS 1 BP 224 EP 231 PG 8 WC Immunology SC Immunology GA TM171 UT WOS:A1996TM17100031 PM 8598466 ER PT J AU Irvine, KR Rao, JB Rosenberg, SA Restifo, NP AF Irvine, KR Rao, JB Rosenberg, SA Restifo, NP TI Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VACCINIA VIRUS-VACCINE; DIRECT GENE-TRANSFER; DOSE RECOMBINANT INTERLEUKIN-2; STIMULATORY FACTOR-II; CYTOTOXIC T-CELLS; IMMUNE-RESPONSES; LYMPHOCYTES-T; ADOPTIVE IMMUNOTHERAPY; PARTICLE BOMBARDMENT; CELLULAR MECHANISMS AB DNA immunization can result in the induction of Ag-specific cellular and humoral immune responses and in protective immunity in several Ag systems. To evaluate the utility of DNA-based immunization as a potential cancer treatment strategy, we employed an experimental murine tumor, CT26, expressing the model tumor-associated Ag, beta-galactosidase (beta-gal), designated CT26,CL25. A plasmid expressing beta-gal (pCMV/beta-gal) administered by particle-mediated gene delivery to the epidermis using a hand-held, helium-driven ''gene gun'' induced beta-gal-specific Ab and lytic responses. Immunization with this construct prevented the growth of pulmonary metastatic tumor, and the adoptive transfer of splenocytes generated by pCMV/beta-gal in vivo immunization and cultured in vitro with the beta-gal(876-884) immunodominant peptide reduced the number of established pulmonary nodules. DNA immunization alone had little or no impact on the growth of established lung metastases. To enhance the function of DNA immunization for active immunotherapy, a panel of cytokines was added as adjuvants following DNA administration, Significant reduction in the number of established metastases was observed when human rlL-2, mouse rlL-6, human rIL-7, or mouse rlL-12 were given after DNA inoculation; mouse rlL-12 as an adjuvant had the most profound effect. These findings suggest that the cytokines involved in the activation and expansion of lymphocyte populations may improve the therapeutic effects of DNA immunization. Given the ease with which plasmid DNA can be prepared to high purity for safe use in humans with infectious diseases and cancers, DNA immunization administered together with cytokine adjuvant may be an attractive alternative to recombinant viral vaccines. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 75 TC 204 Z9 214 U1 2 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 1996 VL 156 IS 1 BP 238 EP 245 PG 8 WC Immunology SC Immunology GA TM171 UT WOS:A1996TM17100033 PM 8598468 ER PT J AU Kim, CJ Taubenberger, JK Simonis, TB White, DE Rosenberg, SA Marincola, FM AF Kim, CJ Taubenberger, JK Simonis, TB White, DE Rosenberg, SA Marincola, FM TI Combination therapy with interferon-gamma and interleukin-2 for the treatment of metastatic melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE interferon-gamma; interleukin-2; melanoma ID PHASE-I TRIAL; TUMOR-INFILTRATING LYMPHOCYTES; HLA CLASS-I; CANCER-PATIENTS; RECOMBINANT INTERLEUKIN-2; NECROSIS-FACTOR; SOLID TUMORS; EXPRESSION; TOXICITY; CELLS AB The toxicity and clinical response to treatment with the combination of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients with metastatic melanoma was evaluated. From May 1993 through February 1994, 20 patients were treated with 24 courses of IFN-gamma with or without IL-2, A 7-day course of subcutaneous IFN-gamma alone was administered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m(2). Thirteen patients received escalating doses of IFN-gamma between 0.2 and 0.5 mg/m(2) followed by the intravenous (i.v.) administration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval, Five additional patients were treated with five courses of IFN-gamma, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated had the diagnosis of metastatic melanoma. The maximal tolerated dose of subcutaneous IFN-gamma was established at 0.3 mg/m(2) with dose-limiting hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combination of IFN-gamma and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial response and 12 months for the complete response. IFN-gamma was tolerated with minimal side effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased toxicities were found with the combination treatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-gamma alone from hemorrhage into brain metastases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-gamma. From these findings, we conclude that further studies looking at this combination treatment are not warranted. C1 NCI, SURG BRANCH,CLIN ONCOL PROGRAM,DIV CANC TREATMENT, NIH, BETHESDA, MD 20892 USA. NIH, DEPT TRANSFUS MED, HLA LAB, BETHESDA, MD USA. ARMED FORCES INST PATHOL, DEPT CELLULAR PATHOL, WASHINGTON, DC 20306 USA. NR 48 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 EI 1537-4513 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 1996 VL 19 IS 1 BP 50 EP 58 DI 10.1097/00002371-199601000-00006 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UG280 UT WOS:A1996UG28000006 PM 8859724 ER PT J AU Rosenberg, SA White, DE AF Rosenberg, SA White, DE TI Vitiligo in patients with melanoma: Normal tissue antigens can be targets for cancer immunotherapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma; vitiligo; immunotherapy; antigens, melanocyte-differentiation ID CYTOLYTIC T-LYMPHOCYTES; ACTIVATED KILLER CELLS; METASTATIC MELANOMA; INTERLEUKIN-2 AB Patients with metastatic renal cell cancer and metastatic melanoma treated with high-dose interleukin-2-based immunotherapy were prospectively evaluated for the development of vitiligo. All patients seen in the Surgery Branch, NCI Immunotherapy Clinic, who had been followed for at least 1 year were evaluated. Of 104 patients with metastatic renal cancer none developed vitiligo, though vitiligo was seen in 11 of 74 (15%) patients with metastatic melanoma (p(2) = 0.0001). No vitiligo was seen in 27 patients who did not respond to immunotherapy, although vitiligo was seen in 11 of 43 (26%) melanoma patients who had an objective response to IL-2-based immunotherapy (p(2) = 0.0002). These findings provide further evidence that the presence of a growing melanoma can sensitize patients to melanocyte-differentiation antigens and that the immune response against these antigens is associated with cancer regression in patients undergoing immunotherapy. RP Rosenberg, SA (reprint author), NCI,SURG BRANCH,CLIN ONCOL PROGRAM,DIV CLIN SCI,NIH,BLDG 10,ROOM 2B42,10 CTR DR,MSC 1502,BETHESDA,MD 20892, USA. NR 20 TC 241 Z9 243 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 1996 VL 19 IS 1 BP 81 EP 84 DI 10.1097/00002371-199601000-00009 PG 4 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UG280 UT WOS:A1996UG28000009 PM 8859727 ER PT J AU Shirai, M Chen, M Arichi, T Masaki, T Nishioka, M Newman, M Nakazawa, T Feinstone, SM Berzofsky, JA AF Shirai, M Chen, M Arichi, T Masaki, T Nishioka, M Newman, M Nakazawa, T Feinstone, SM Berzofsky, JA TI Use of intrinsic and extrinsic helper epitopes for in vivo induction of anti-hepatitis C virus cytotoxic T lymphocytes (CTL) with CTL epitope peptide vaccines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NON-B-HEPATITIS; CHRONIC NON-A; MHC CLASS-II; ENVELOPE GLYCOPROTEIN; SYNTHETIC PEPTIDE; CELL EPITOPES; HTLV-III; RESPONSES; HIV-1; MOLECULES AB The induction of virus-specific cytotoxic T lymphocytes (CTL) is an important part of vaccine strategy, CTL induction in vivo by two hepatitis C virus (HCV) peptides containing CTL epitopes, one from the NS5 region (P17) and one from the core (C7), was compared, P17 required covalent attachment of a helper peptide (PCLUS3 containing a cluster of epitopes from the human immunodeficiency virus envelope protein), whereas C7 did not, However, the minimal decapeptide of C7, C7A10, alone did not induce CTL. The helper cells induced by PCLUS3-17 or by C7 were shown to be CD4(+) and to produce interleukin-2 (IL-2), Thus, help can be supplied by a natural helper epitope intrinsic to the CTL peptide, as in C7, or by attaching a helper epitope from another protein, as in the case of P17, The cluster peptides may be useful promiscuous helper peptides for a variety of CTL epitopes from diverse pathogens. C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,LAB HEPATITIS RES,BETHESDA,MD. YAMAGUCHI UNIV,SCH MED,DEPT MICROBIOL,YAMAGUCHI,JAPAN. KAGAWA MED SCH,DEPT INTERNAL MED 3,KAGAWA,JAPAN. CAMBRIDGE BIOTECH CORP,WORCESTER,MA. NR 49 TC 42 Z9 42 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 1996 VL 173 IS 1 BP 24 EP 31 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TM343 UT WOS:A1996TM34300005 PM 8537666 ER PT J AU Clements, ML Makhene, MK Karron, RA Murphy, BR Steinhoff, MC Subbarao, K Wilson, MH Wright, PF AF Clements, ML Makhene, MK Karron, RA Murphy, BR Steinhoff, MC Subbarao, K Wilson, MH Wright, PF TI Effective immunization with live attenuated influenza A virus can be achieved in early infancy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID COLD-ADAPTED INFLUENZA; WILD-TYPE VIRUS; REASSORTANT VIRUS; A-VIRUS; YOUNG-CHILDREN; AVIAN-HUMAN; INACTIVATED VACCINE; INFECTION; H1N1; ADULTS AB The immunogenicity of vaccines can be modified in infancy by maternal antibodies and other immunizations, Hence, the safety and immunogenicity of two doses of 10(7) TCID50 of live, attenuated cold-adapted (ca) influenza A/Kawasaki/86 (H1N1) reassortant virus vaccine given with or apart from childhood immunizations were evaluated in infants, starting at 2, 4, or >6 months of age, in randomized, double-blind trials, The ca vaccine was safe and did not significantly reduce the immunogenicity of the childhood vaccines in these infants. Infectivity of ca virus (virus shedding, greater than or equal to 4-fold rise in serum hemagglutination inhibition antibody titer, or both) was affected by age, quantity of ca virus given, and prior ca virus infection. Two doses of 10(7) TCID50 of ca influenza virus infected all infants, indicating that both doses are probably needed to achieve immunity against influenza in infants <6 months of age. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. PEDIAT CARE CTR,BETHESDA,MD. VANDERBILT UNIV,MED CTR,DEPT PEDIAT,NASHVILLE,TN 37232. RP Clements, ML (reprint author), JOHNS HOPKINS UNIV,CTR IMMUNIZAT RES,SCH PUBL HLTH,DEPT INT HLTH,HAMPTON HOUSE 125,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [AI-15095] NR 38 TC 37 Z9 38 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 1996 VL 173 IS 1 BP 44 EP 51 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TM343 UT WOS:A1996TM34300008 PM 8537681 ER PT J AU Montefiori, DC Pantaleo, G Fink, LM Zhou, JT Zhou, JY Bilska, M Miralles, GD Fauci, AS AF Montefiori, DC Pantaleo, G Fink, LM Zhou, JT Zhou, JY Bilska, M Miralles, GD Fauci, AS TI Neutralizing and infection-enhancing antibody responses to human immunodeficiency virus type 1 in long-term nonprogressors SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID DEPENDENT ENHANCEMENT; HIV-1 INFECTION; RECOMBINANT GP160; HUMAN-MONOCYTES; COMPLEMENT; INDIVIDUALS; RECIPIENTS; VACCINE; INVITRO; BINDING AB Serum antibodies from human immunodeficiency virus type 1 (HIV-1)-infected long-term nonprogressors (LTNPs) and non-LTNPs were evaluated for virus neutralization and infection enhancement in vitro. Sera from LTNPs had higher average titers of neutralizing antibodies to HIV-1 strains IIIB and MN and more frequently neutralized primary isolates from progressors (14.9% vs, 1.3%, P = .002). Replication-competent HIV-1 was isolated from peripheral blood mononuclear cells and lymph nodes of 3 LTNPs. All viruses from LTNPs had a non-syncytium-inducing phenotype, were resistant to neutralization by autologous serum obtained at the time of virus isolation, and showed little evidence of a heightened sensitivity to neutralization by heterologous sera. Complement-mediated, antibody-dependent enhancement (C'-ADE) of HIV-1(IIIB) and primary isolates was equally prevalent for sera from LTNPs and non-LTNPs. Results indicate that LTNPs produce vigorous serum antibody responses and that long-term nonprogression is not associated with homologous neutralization or the absence of C'-ADE. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP Montefiori, DC (reprint author), DUKE UNIV,MED CTR,DEPT SURG,POB 2926,DURHAM,NC 27710, USA. RI Pantaleo, Giuseppe/K-6163-2016 FU NIAID NIH HHS [AI-28662, AI-45218] NR 43 TC 221 Z9 226 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 1996 VL 173 IS 1 BP 60 EP 67 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TM343 UT WOS:A1996TM34300010 PM 8537683 ER PT J AU Leport, C Chene, G Morlat, P Luft, BJ Rousseau, F Pueyo, S Hafner, R Miro, J Aubertin, J Salamon, R Vilde, JL Blanc, AP Schmitt, JL Arlaud, J Estavoyer, JM Guillevin, L Bentata, M Beylot, J Lacut, JY Granier, P Cosnard, F Bazin, C Dormont, J Rey, M Delaunay, C Troisvallet, D Micoud, M Weinbreck, P Trepo, C Gallais, H Gastaut, JA Allard, C Janbon, F Canton, P Grolleau, JY Cassuto, J Dellamonica, P Duret, P Frottier, J Herson, S Seligmann, M Sereni, D Giraudon, BB Dien, G Ruel, M Storck, D Jaubert, D Lafeuillade, A Mouton, Y Choutet, P Lafaix, C Gatell, JM Guelar, A Mildvan, D Soiero, R Jacobson, JM Murray, HW Steigbigel, NH Sachs, HH Valentine, F Grieco, MH Armstrong, D Lederman, M Bartlett, JA Waskin, HA Nicholas, P Fessel, JW MacArthur, RD Glatt, AE Phair, JP Powderly, W Hewitt, R Steigbigel, RT Blair, DC Skahan, KJ Frame, P Cheeseman, SH Connor, EM Balfour, HH VanderHorst, C Ho, M AF Leport, C Chene, G Morlat, P Luft, BJ Rousseau, F Pueyo, S Hafner, R Miro, J Aubertin, J Salamon, R Vilde, JL Blanc, AP Schmitt, JL Arlaud, J Estavoyer, JM Guillevin, L Bentata, M Beylot, J Lacut, JY Granier, P Cosnard, F Bazin, C Dormont, J Rey, M Delaunay, C Troisvallet, D Micoud, M Weinbreck, P Trepo, C Gallais, H Gastaut, JA Allard, C Janbon, F Canton, P Grolleau, JY Cassuto, J Dellamonica, P Duret, P Frottier, J Herson, S Seligmann, M Sereni, D Giraudon, BB Dien, G Ruel, M Storck, D Jaubert, D Lafeuillade, A Mouton, Y Choutet, P Lafaix, C Gatell, JM Guelar, A Mildvan, D Soiero, R Jacobson, JM Murray, HW Steigbigel, NH Sachs, HH Valentine, F Grieco, MH Armstrong, D Lederman, M Bartlett, JA Waskin, HA Nicholas, P Fessel, JW MacArthur, RD Glatt, AE Phair, JP Powderly, W Hewitt, R Steigbigel, RT Blair, DC Skahan, KJ Frame, P Cheeseman, SH Connor, EM Balfour, HH VanderHorst, C Ho, M TI Pyrimethamine for primary prophylaxis of toxoplasmic encephalitis in patients with human immunodeficiency virus infection: A double-blind, randomized trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; NERVOUS-SYSTEM TOXOPLASMOSIS; TRIMETHOPRIM-SULFAMETHOXAZOLE; AEROSOLIZED PENTAMIDINE; DAPSONE-PYRIMETHAMINE; AIDS; THERAPY; GONDII; COTRIMOXAZOLE; SULFADIAZINE AB Pyrimethamine (50 mg) with folinic acid (15 mg) given three times weekly was assessed as primary prophylaxis for toxoplasmic encephalitis (TE) in 554 human immunodeficiency virus-infected patients seropositive for Toxoplasma gondii and with <200 CD4 cells/mm(3). At 1 year, the incidence of TE was similar in pyrimethamine, 12%, and placebo, 13%, groups (relative risk [RR], 0.9; 95% confidence interval [CI], 0.6-1.4), and the survival rate was also similar, 85% and 80%, respectively (RR, 0.9; 95% CI, 0.7-1.2). Rash was the only adverse event that appeared significantly more frequently in the pyrimethamine arm (7% vs. 1%), In the on-treatment analysis, the incidence of TE was lower in the pyrimethamine arm, 4%, than in the placebo arm, 12% (P < .006). Thus, pyrimethamine cannot be recommended as a first-line regimen for primary prophylaxis of TE if the patient can take cotrimoxazole. However, it should be considered for patients who are intolerant to cotrimoxazole, especially in high-risk patients with <100 CD4 cells/mm(3). C1 UNIV BORDEAUX 2,INSERM U330,DEPT MED INFORMAT,F-33076 BORDEAUX,FRANCE. HOP PELLEGRIN,CLIN MED & MALAD INFECT,F-33076 BORDEAUX,FRANCE. SUNY STONY BROOK,DEPT MED,DIV INFECT DIS,STONY BROOK,NY 11794. NIAID,DIV AIDS,BETHESDA,MD 20892. HOSP CLIN BARCELONA,INFECT DIS UNIT,BARCELONA,SPAIN. RP Leport, C (reprint author), UNIV PARIS 07,HOP BICHAT,SERV MALAD INFECT & TROP,46 RUE HENRI HUCHARD,F-75877 PARIS 18,FRANCE. RI chene, genevieve/H-8665-2014; OI Luft, Benjamin/0000-0001-9008-7004 NR 36 TC 54 Z9 58 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 1996 VL 173 IS 1 BP 91 EP 97 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TM343 UT WOS:A1996TM34300014 PM 8537688 ER PT J AU Blazka, ME Germolec, DR Simeonova, P Bruccoleri, A Pennypacker, KR Luster, MI AF Blazka, ME Germolec, DR Simeonova, P Bruccoleri, A Pennypacker, KR Luster, MI TI Acetaminophen-induced hepatotoxicity is associated with early changes in NF-kappa B and NF-IL6 DNA binding activity SO JOURNAL OF INFLAMMATION LA English DT Article DE liver; immunohistochemistry; transcription factors; parenchymal cell; Kupffer cell ID FACTOR-KAPPA-B; TRANSCRIPTION FACTORS; EXPRESSION; ACTIVATION; LIVER; HEPATOCYTES; SUBUNIT; GENE; RAT; INTERLEUKIN-6 AB Nuclear transcription factors, such as NF-B and NF-IL6, are believed to play an important role in regulating the expression of genes that encode for products involved in tissue damage and inflammation and, thus, may represent early biomarkers for chemical toxicities. In the present study changes in DNA binding activity of these factors were examined in livers of mice administered hepatotoxic doses of acetaminophen (APAP). NF-kB and NF-IL6 DNA binding occurred constitutively in control mouse liver. However, within 4 hr following administration of hepatotoxic doses of APAP, their binding activities were transiently lost and is in contrast to AP-1 transcription factor where activation occurs under similar conditions. These changes corresponded with increased release of inflammatory mediators (IL-6, serum amyloid A) and increased levels of enzymatic markers of hepatocyte damage. Similarly, treatment of mice with gadolinium chloride, an inhibitor of Kupffer cell activation and known to protect against APAP-induced hepatotoxicity, reduced the observed pathophysiological response in the liver while altering the APAP-associated changes in NF-kB DNA binding activity. NF-kB was found predominantly in parenchymal and endothelial cells mad was composed primarily of relatively inactive p50 homodimer subunits in control liver. Taken together, these studies suggest that hepatotoxicity is associated with early and complex changes in DNA binding activities of specific transcription factors. fn particular NF-kB and NF-IL6 may serve as negative regulators of hepatocyte-derived inflammatory mediators and is analogous to that previously observed in certain other cell systems such as B lymphocytes. (C) 1997 Wiley-Liss, Inc. C1 NIOSH,HELD,MORGANTOWN,WV 26505. NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. UNIV S FLORIDA,DEPT THERAPEUT & PHARMACOL,TAMPA,FL. RI Pennypacker, Keith/I-5092-2012 NR 29 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1078-7852 J9 J INFLAMM JI J. Inflamm. PY 1996 VL 47 IS 3 BP 138 EP 150 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Hematology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Hematology; Immunology GA WF055 UT WOS:A1996WF05500003 ER PT J AU Stuber, F Udalova, IA Book, M Drutskaya, LN Kuprash, DV Turetskaya, RL Schade, FU Nedospasov, SA AF Stuber, F Udalova, IA Book, M Drutskaya, LN Kuprash, DV Turetskaya, RL Schade, FU Nedospasov, SA TI 308 tumor necrosis factor (TNF) polymorphism is not associated with survival in severe sepsis and is unrelated to lipopolysaccharide inducibility of the human TNF promoter SO JOURNAL OF INFLAMMATION LA English DT Article DE TNF; sepsis; LPS; macrophage; gene; polymorphism; transcription ID DEPENDENT DIABETES-MELLITUS; ORGAN FAILURE; ALPHA GENE; KAPPA-B; BETA; MACROPHAGES; LYMPHOTOXIN; BACTEREMIA; CACHECTIN; CHILDREN AB Tumor necrosis factor (TNF) is recognized as a central mediator of sepsis, septic shock, and multiple organ failure. These host reactions are associated with increased TNF levels in circulation, presumably due to increased TNF production. A previously described nucleotide variation at position -308 in the promoter region of the human TNF gene was shown to be associated with the clinical outcome of malaria. In this study we addressed the relevance of the -308 polymorphism for expression of the human TNF gene in response to bacterial endotoxin in vivo and in vitro. First, we typed 80 patients suffering from severe sepsis and 153 healthy individuals and found no association of the -308 variation with incidence of the disease. In contrast the NcoI marker in the closely linked lymphotoxin-alpha (LT-alpha) gene showed association with survival. This discrepancy can be explained by the linkage of the TNFB2 (NcoI) allele to the common TNF1 (-308) allele. Second toe generated reporter gene constructs with promoter deletions and with both -308 variation in the context of the extended human TNF promoter region. Although such constructs were highly inducible by lipopolysaccharide (LPS) in transient transfections into a macrophage cell line, the -308 variation had no significant effect on transcription, consistent with the promoter deletion study. We conclude that the functional consequence of the -308 polymorphism may be unrelated to transcriptional response of the TNF gene to bacterial endotoxin. (C) 1996 Wiley-Liss, Inc. C1 UNIV HOSP,CLIN RES GRP SHOCK & MULTIPLE ORGAN FAILURE,ESSEN,GERMANY. RUSSIAN ACAD SCI,ENGELHARDT INST MOLEC BIOL,LAB CYTOKINE MOLEC BIOL,MOSCOW,RUSSIA. BELOZERSKY PHYSICOCHEM BIOL INST,MOSCOW,RUSSIA. SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,DIV BASIC SCI,FREDERICK,MD 21702. RP Stuber, F (reprint author), CHRISTIAN ALBRECHTS UNIV KIEL,CLIN ANESTHESIOL & INTENS CARE MED,D-24105 KIEL,GERMANY. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 41 TC 165 Z9 171 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1078-7852 J9 J INFLAMM JI J. Inflamm. PY 1996 VL 46 IS 1 BP 42 EP 50 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Hematology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Hematology; Immunology GA UA114 UT WOS:A1996UA11400006 ER PT J AU Shearer, GM AF Shearer, GM TI Molecular medicine: Cytokines in health and disease SO JOURNAL OF INFLAMMATION LA English DT Editorial Material RP Shearer, GM (reprint author), NCI,EXPTL IMMUNOL BRANCH,NIH,BLDG 10,BETHESDA,MD 20892, 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 SN 1078-7852 J9 J INFLAMM JI J. Inflamm. PY 1996 VL 46 IS 1 BP 61 EP 63 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Hematology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Hematology; Immunology GA UA114 UT WOS:A1996UA11400008 ER PT J AU Pan, MG Xiong, J Copeland, NG Gilbert, DJ Jenkins, NA Goeddel, DV AF Pan, MG Xiong, J Copeland, NG Gilbert, DJ Jenkins, NA Goeddel, DV TI Sequence, genomic organization, and chromosome localization of the mouse TRADD gene SO JOURNAL OF INFLAMMATION LA English DT Article DE tumor necrosis factor; TNF-R1; TRADD, NF-kappa B; apoptosis; cell death; gene structure; gene expression; chromosome localization ID NECROSIS-FACTOR RECEPTOR; DEATH DOMAIN; CELL-DEATH; TNF RECEPTOR; PROTEIN; INTERACTS; MONOCYTOGENES; APOPTOSIS; RESISTANT; INFECTION AB Signals triggered by tumor necrosis factor (TNF) are mediated by its two receptors: the 55 kDa TNF receptor one (TNF-R1) and the 75 kDa TNF receptor two (TNF-R2). Activation of TNF-R1 induces cell death, NF-kappa B activation, inflammatory response and anti-viral activity, while TNF-R2 mainly stimulates cell proliferation and NF-kappa B activation. The TNF-R2-associated factor TRAF2 has been shown to mediate activation of NF-kappa B by TNF-R2 and CD40. The human TNF-R1-associated death domain protein (TRADD) induces cell death and NF-kappa B activation when overexpressed. Here we describe the clotting and gene structure of the mouse homolog of TRADD. Mouse TRADD shares 75% overall amino acid sequence identity with human TRADD, suggesting high conservation of function. Mouse TRADD specifically interacts with wild type TNF-R1 but not with a truncated mutant TNF-R1 lacking its C-terminal 20 amino acids. Like human TRADD, mouse TRADD also induces activation of NF-kappa B and cell death. The expression of TRADD in mouse embryo appears developmentally regulated. The mTRADD gene contains four exerts, with the fourth exon encoding all of the death domain. The mouse TRADD gene was localized to the distal region of chromosome 8. (C) 1996 Wiley-Liss, Inc. C1 TULARIK INC,DEPT MOL BIOL,S SAN FRANCISCO,CA 94080. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 29 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1078-7852 J9 J INFLAMM JI J. Inflamm. PY 1996 VL 46 IS 3 BP 168 EP 175 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Hematology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Hematology; Immunology GA VA324 UT WOS:A1996VA32400005 ER PT J AU Matern, D Niederhoff, H Brandis, M Chou, JY AF Matern, D Niederhoff, H Brandis, M Chou, JY TI Verification of diagnosis in a 17-year-old boy with clinical glycogen storage disease type Ia by mutation screening SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-the-Study-of-Inborn-Errors-of-Metabolism CY SEP 12-15, 1995 CL TOLEDO, OH SP Soc Study Inborn Errors Metabolism C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. RP Matern, D (reprint author), UNIV FREIBURG,CHILDRENS HOSP,MATHILDENSTR 1,D-79106 FREIBURG,GERMANY. NR 8 TC 6 Z9 6 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PY 1996 VL 19 IS 2 BP 205 EP 208 DI 10.1007/BF01799430 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA UJ354 UT WOS:A1996UJ35400027 PM 8739966 ER PT J AU Puri, SK Dutta, GP Levy, HB Maheshwari, RK AF Puri, SK Dutta, GP Levy, HB Maheshwari, RK TI Poly ICLC inhibits Plasmodium cynomolgi B malaria infection in rhesus monkeys SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID GAMMA-INTERFERON; L-LYSINE; CANCER; ACID; HEPATOCYTES; PARASITES; INDUCTION; COMPLEX AB Prophylatic treatment with a single dose of 1.0 or 2.0 mg/kg (body weight) of polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (Poly ICLC), a potent interferon (IFN) inducer and immune enhancer, 18 h before intravenous inoculation of sporozoites (1.04 x 10(5)-0.70 x 10(6) sporozoites) of Plasmodium cynomolgi B in the rhesus monkey, completely abolished the infectivity of sporozoites. The inhibitory effect of Poly ICLC is dose dependent in monkeys infected with P. cynomolgi B sporozoites. Treatment with lower doses of Poly ICLC (0.5 mg/kg) provided significant protection, but the lowest dose of Poly ICLC used (0.1 mg/kg) failed to provide any protection. Prophylactic treatment with Poly ICLC, however, had no protective effect against trophozoite-induced infection. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. CENT DRUG RES INST,LUCKNOW 226001,UTTAR PRADESH,INDIA. NIAID,BETHESDA,MD 20892. NR 33 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD JAN PY 1996 VL 16 IS 1 BP 49 EP 52 DI 10.1089/jir.1996.16.49 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA TR264 UT WOS:A1996TR26400008 PM 8640451 ER PT B AU Harris, CC AF Harris, CC BE OKeefe, E TI p53: At the crossroads of molecular carcinogenesis and molecular epidemiology SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS, VOL 1, NO 2, APRIL 1996: SKIN CANCER: PATHOMECHANISMS, EPIDEMIOLOGY AND CLINICAL MANIFESTATIONS AND NEW APPROACHES TO TREATMENT - MELANOMA CELL ADHESION MOLECULE LA English DT Proceedings Paper CT 44th Annual Symposium on the Biology of Skin - Skin Cancer: Pathomechanisms, Epidemiology and Clinical Manifestations and New Approaches to Treatment CY JUL 11-15, 1995 CL SNOWMASS, CO SP Natl Psoriasis Fdn, Estee Lauder, Orentreich Fdn Adv Sci, Burroughs Wellcome, Beiersdorf Inc, Glaxo Dermatol, Procter & Gamble Pharm, Amgen Inc AB The p53 tumor suppressor gene is frequently mutated in human cancer, including squamous cell carcinoma and basal cell carcinoma of the skin, but is rarely mutated in skin melanoma. The p53 mutation spectrum provides insight into both the etiology of human cancer and the functional regions of the encoded protein that lead to clonal expansion of the p53 mutant cell. RP Harris, CC (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C01,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA COMMERCE PLACE 350 MAIN ST, MALDEN, MA 02148 PY 1996 BP 115 EP 118 PG 4 WC Dermatology SC Dermatology GA BG97M UT WOS:A1996BG97M00001 ER PT B AU Yuspa, SH Dlugosz, AA Denning, MF Glick, AB AF Yuspa, SH Dlugosz, AA Denning, MF Glick, AB BE OKeefe, E TI Multistage carcinogenesis in the skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS, VOL 1, NO 2, APRIL 1996: SKIN CANCER: PATHOMECHANISMS, EPIDEMIOLOGY AND CLINICAL MANIFESTATIONS AND NEW APPROACHES TO TREATMENT - MELANOMA CELL ADHESION MOLECULE LA English DT Proceedings Paper CT 44th Annual Symposium on the Biology of Skin - Skin Cancer: Pathomechanisms, Epidemiology and Clinical Manifestations and New Approaches to Treatment CY JUL 11-15, 1995 CL SNOWMASS, CO SP Natl Psoriasis Fdn, Estee Lauder, Orentreich Fdn Adv Sci, Burroughs Wellcome, Beiersdorf Inc, Glaxo Dermatol, Procter & Gamble Pharm, Amgen Inc DE keratinocytes; protein kinase C; epidermal growth factor receptor; transforming growth factor beta AB The multistage evolution of squamous cell cancer on mouse skin has provided a model to dissect the biological and genetic changes that contribute to specific stages of carcinogenesis, Keratinocyte cell culture models have been developed that reproduce the genetic and epigenetic events in multistage skin carcinogenesis, and these provide insights into the biochemistry of the process. When the v-ras(Ha) oncogene is transduced into normal mouse keratinocytes, the resultant papilloma phenotype is characterized by a high rate of cell proliferation, an aberrant program of differentiation marker expression, and resistance to terminal differentiation. These changes are attributed to differential effects on isoforms of protein kinase C coupled to activation of the epidermal growth factor receptor, Premalignant progression requires additional genetic changes in the v-ras(Ha)-transduced cells, The acquisition of these changes is suppressed by transforming growth factor beta (TGF beta), and the absence of TGF beta in premalignant tumors indicates a high risk for malignant progression, Keratinocytes that are genetically null for the TGF beta 1 gene rapidly progress to squamous cell carcinomas when transduced with the v-ras(Ha) oncogene. In culture, TGF beta 1 null keratinocytes exhibit a high rate of gene amplification that can be suppressed by concentrations of exogenous TGF beta well below those required to inhibit proliferation. This model is well-suited to identifying critical genetic changes that contribute to premalignant progression. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV CANC ETIOL,BETHESDA,MD 20892. RP Yuspa, SH (reprint author), BLDG 37,ROOM 3B25,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA COMMERCE PLACE 350 MAIN ST, MALDEN, MA 02148 PY 1996 BP 147 EP 150 PG 4 WC Dermatology SC Dermatology GA BG97M UT WOS:A1996BG97M00007 ER PT B AU Tennenbaum, T Belanger, AJ Quaranta, V Yuspa, SH AF Tennenbaum, T Belanger, AJ Quaranta, V Yuspa, SH BE OKeefe, E TI Differential regulation of integrins and extracellular matrix binding in epidermal differentiation and squamous tumor progression SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS, VOL 1, NO 2, APRIL 1996: SKIN CANCER: PATHOMECHANISMS, EPIDEMIOLOGY AND CLINICAL MANIFESTATIONS AND NEW APPROACHES TO TREATMENT - MELANOMA CELL ADHESION MOLECULE LA English DT Proceedings Paper CT 44th Annual Symposium on the Biology of Skin - Skin Cancer: Pathomechanisms, Epidemiology and Clinical Manifestations and New Approaches to Treatment CY JUL 11-15, 1995 CL SNOWMASS, CO SP Natl Psoriasis Fdn, Estee Lauder, Orentreich Fdn Adv Sci, Burroughs Wellcome, Beiersdorf Inc, Glaxo Dermatol, Procter & Gamble Pharm, Amgen Inc DE alpha 6 beta 4; laminin; keratinocytes; skin cancer AB Cell surface receptors of the integrin family regulate physiological and pathological processes in skin, including proliferation, diffrentiation, and malignant transformation. In skin, integrins are compartmentalized, While alpha 6 beta 4 is restricted to the basal surface of basal cells, beta 1. integrins are expressed in basal and suprabasal layers, In vivo and in Ca2+-induced differentiation of mouse keratinocytes in vitro, the loss of attachment to laminin via alpha 6 beta 4 integrin is an early event associated with initiation of spinous differentiation, The restricted expression of alpha 6 beta 4 to the basal cells in normal skin is disrupted early in the development of squamous cancer, where benign papillomas at high risk for malignant progression express alpha 6 beta 4 suprabasally in an expanded proliferative compartment, The aberrant suprabasal alpha 6 beta 4 is associated with reduced keratin 1 expression and upregulation of keratin 13, keratin 8, and gamma-glutamyltranspeptidase, During malignant conversion, the increase in alpha 6 beta 4 protein and mRNA is associated with novel expression of an alternatively spliced form of the alpha 6 subunit, alpha 6B. The induction of alpha 6B both in vivo and in vitro is particularly high in malignant cells produced by transduction of both v-fos and v-ras(Ha) oncogenes into normal keratinocytes where it was associated with increased attachment to laminin. Furthermore binding to laminin is increased by introduction of alpha 6B into a papilloma cell line, These results establish a link between squamous tumor progression and the upregulation of the alpha 6 beta 4 integrin and suggest that expression of alpha 6B could be functionally relevant to interaction df tumor cells with the laminin matrix during malignant conversion. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,DIV CANC ETIOL,BETHESDA,MD 20892. RP Yuspa, SH (reprint author), BLDG 37,ROOM 3B25,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA COMMERCE PLACE 350 MAIN ST, MALDEN, MA 02148 PY 1996 BP 157 EP 161 PG 3 WC Dermatology SC Dermatology GA BG97M UT WOS:A1996BG97M00009 ER PT J AU Clark, KF Slymen, DJ Schneider, JA Thoene, JG Gahl, WA Sebring, NG Parisi, R AF Clark, KF Slymen, DJ Schneider, JA Thoene, JG Gahl, WA Sebring, NG Parisi, R TI Indomethacin therapy for the short-term treatment of the Fanconi syndrome in cistinosis SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,DEPT PEDIAT,LA JOLLA,CA 92093. SAN DIEGO STATE UNIV,GRAD SCH PUBL HLTH,SAN DIEGO,CA 92182. UNIV MICHIGAN,ANN ARBOR,MI 48109. NICHHD,CTR CLIN,DEPT NUTR,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 1996 VL 44 IS 1 BP A169 EP A169 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TP690 UT WOS:A1996TP69000901 ER PT J AU Coleman, M Fairbanks, V Merritt, D Rodgers, G Thibodeau, S Steinberg, M Jones, R AF Coleman, M Fairbanks, V Merritt, D Rodgers, G Thibodeau, S Steinberg, M Jones, R TI Compound heterozygosity for alpha thalassemia-2 and hemoglobin seal rock produces mild Hb H disease: The alpha-globin chain mutation in Hb seal rock is a TAA->GAA transversion in the termination codon of the 5' alpha 2-globin gene. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 VET ADM MED CTR,ST LOUIS,MO 63125. UNIV MISSISSIPPI,DEPT MED,ST LOUIS,MO. UNIV WASHINGTON,ST LOUIS,MO. NIH,BETHESDA,MD 20892. MAYO CLIN,ROCHESTER,MN. UNIV OREGON,PORTLAND,OR. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 1996 VL 44 IS 1 BP A36 EP A36 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TP690 UT WOS:A1996TP69000203 ER PT J AU Krakow, D Biesecker, L VanDop, C Lachman, RS Rimoin, DL Graham, JM AF Krakow, D Biesecker, L VanDop, C Lachman, RS Rimoin, DL Graham, JM TI Acrodysostosis: Is it a G protein abnormality? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,CEDARS SINAI MED CTR,CTR MED GENET BIRTH DEFECTS,LOS ANGELES,CA. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 1996 VL 44 IS 1 BP A131 EP A131 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TP690 UT WOS:A1996TP69000698 ER PT J AU Shinar, RZ Sikorski, RS Varmus, HE AF Shinar, RZ Sikorski, RS Varmus, HE TI In vivo gene targeting to the mouse mammary gland using cationic lipids SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 UNIV CALIF SAN DIEGO,SCH MED,LA JOLLA,CA 92093. NCI,VARMUS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 1996 VL 44 IS 1 BP A166 EP A166 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TP690 UT WOS:A1996TP69000884 ER PT J AU Eden, G AF Eden, G TI Untitled - Response SO JOURNAL OF LEARNING DISABILITIES LA English DT Letter ID DEVELOPMENTAL DYSLEXIA; CORTEX RP Eden, G (reprint author), NIMH,SECT FUNCT BRAIN IMAGING,BETHESDA,MD 20892, USA. NR 14 TC 0 Z9 0 U1 3 U2 3 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK BLVD, AUSTIN, TX 78757-6897 SN 0022-2194 J9 J LEARN DISABIL JI J. Learn. Disabil. PD JAN PY 1996 VL 29 IS 1 BP 5 EP & PG 3 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA TP329 UT WOS:A1996TP32900004 ER PT J AU Taub, DD Ortaldo, JR TurcovskiCorrales, SM Key, ML Longo, DL Murphy, WJ AF Taub, DD Ortaldo, JR TurcovskiCorrales, SM Key, ML Longo, DL Murphy, WJ TI beta Chemokines costimulate lymphocyte cytolysis, proliferation, and lymphokine production SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT 4th International Chemokine Symposium - Molecules to Disease CY JUN 27-30, 1995 CL BATH, ENGLAND DE MIP-1 alpha; MIP-1 beta; RANTES; MCP-1; cytotoxic T lymphocytes; natural killer cells ID NATURAL-KILLER-CELLS; T-CELLS; ANTIGEN RECEPTOR; INTERLEUKIN-2; MIP-1-BETA; BIOLOGY; FAMILY; GROWTH AB We report here the ability of the beta chemokines MIP-1 alpha, MIP-1 beta, RANTES, acid MCP-1 to enhance some lymphocyte effector functions, Initial studies focused on the effects of chemokines on human and mouse cytotoxic T lymphocyte (CTL)- and natural killer (NK) cell-specific cytolytic responses. The results demonstrate that beta chemokines are capable of augmenting mouse and human CTL and human NK- but not lymphokine-activated killer cell- or antibody-dependent cell cytotoxicity-specific: cytolytic responses, Neutralization analysis utilizing integrin-specific antibodies revealed that CTL/NK-tunor cell conjugate formation is required for chemokine-induced killing, In addition, both CTLs and NK cells incubated with various beta chemokines were induced to degranulate and release granule-derived serine esterases, suggesting that chemokines may be important costimulators of CTL and NK sell degranulation and may thus augment local target cell destruction, Chemokines also modulate antigen-driven T cell proliferative responses as well as effects on lymphokine production, Many of the beta chemokines were found to potentiate human and mouse antigen-specific Th1 and Th2 clone activation promoting cellular proliferation and the release of various lymphokines, This chemokine-mediated T cell proliferation was chemokine and antigen dose dependent as well as clone dependent. Chemokine pretreatment analyses with T cells and antigen-presenting cells (APCs) revealed that chemokines up-regulate both T cell and APC functions, Costimulation assays using immobilized anti-CD3 monoclonal antibody-coated plates and purified human and mouse T cells and T cell clones in the presence of various chemokines also exhibited enhanced proliferation and lymphokine secretion, This costimulation was interleukin-2 dependent and required the presence of free extracellular calcium, Examination of chemokine-treated APCs revealed that the T cell costimulatory molecule B7-1 was induced by various beta chemokines, Neutralization of endogenously produced chemokines with specific antibodies during an antigen-specific T cell response blocked cellular proliferation, suggesting that the chemokines have an autocrine and/or paracrine role in antigen-induced T cell proliferative responses, Together, these results suggest that chemokines play a significant role in the activation of polyclonal as well as antigen-specific helper and cytotoxic T cells during the genesis of an immune response. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP Taub, DD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,SERV CLIN PROGRAM,BLDG 560,ROOM 11-23,FREDERICK,MD 21702, USA. NR 33 TC 187 Z9 192 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 1996 VL 59 IS 1 BP 81 EP 89 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA TR604 UT WOS:A1996TR60400013 PM 8558072 ER PT J AU Young, HA Cippitelli, M Ye, J Ghosh, P Viggiano, V Mikovits, J Ruscetti, F Dorman, L Sica, A AF Young, HA Cippitelli, M Ye, J Ghosh, P Viggiano, V Mikovits, J Ruscetti, F Dorman, L Sica, A TI Regulation of interferon-gamma gene expression: Multiple mechanisms of control. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,LEI,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,IRSP,SAIC FREDERICK,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,LLB,DBS,FREDERICK,MD. 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 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1996 SU S BP 2 EP 2 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA VE906 UT WOS:A1996VE90600003 ER PT J AU Langenbach, R Chulada, PC Lee, CA Morham, SG Tiano, HF AF Langenbach, R Chulada, PC Lee, CA Morham, SG Tiano, HF TI Inflammatory responses in cyclooxygenase 1 and 2 deficient mice. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27511. NIEHS,RES TRIANGLE PK,NC 27709. 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 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1996 SU S BP 11 EP 11 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA VE906 UT WOS:A1996VE90600011 ER PT J AU Musso, T Bresciani, S Ponzi, AN Wang, JM Turano, A Badolato, R AF Musso, T Bresciani, S Ponzi, AN Wang, JM Turano, A Badolato, R TI Serum amyloid a enhances PMN-mediated anti-candida activity and stimulates the production of anion superoxide. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 UNIV TURIN,INST MICROBIOL,I-10124 TURIN,ITALY. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,IRSP,FREDERICK,MD. UNIV BRESCIA,DEPT PEDIAT,BRESCIA,ITALY. UNIV BRESCIA,DEPT MICROBIOL,BRESCIA,ITALY. RI Badolato, Raffaele/A-8081-2010 OI Badolato, Raffaele/0000-0001-7375-5410 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 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1996 SU S BP 164 EP 164 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA VE906 UT WOS:A1996VE90600165 ER PT J AU Badgett, A Bonner, JC Brody, AR AF Badgett, A Bonner, JC Brody, AR TI Interferon-gamma modulates lung macrophage production of PDGF-BB and fibroblast growth SO JOURNAL OF LIPID MEDIATORS AND CELL SIGNALLING LA English DT Article DE interferon-gamma; PGDF; fibroblast growth; lung macrophage ID NONSMOKING INDIVIDUALS; ALVEOLAR MACROPHAGES; PULMONARY FIBROSIS; IMMUNE INTERFERON; PROLIFERATION; ASBESTOS; CELLS; GENES; RECEPTORS; PROTEIN AB Platelet-derived growth factor (PDGF) is a potent mediator of fibroblast proliferation and chemotaxis. We have studied here the cytokine interferon-gamma (IFN-gamma) which is known to prime macrophages for increased PDGF production. Thus, we postulated that IFN-gamma would act as a positive regulator of PDGF-BB secretion by rat alveolar macrophages, and in addition we asked whether or not the IFN-gamma (a known anti-mitogenic cytokine) would block the growth response of primary lung fibroblasts to the PDGF-BB. Macrophages incubated with IFN-gamma or iron spheres alone for 24 h secreted 2.5-fold more PDGF-BB than control macrophages incubated in serum-free medium. Preincubation of macrophages with IFN-gamma prior to the addition of iron spheres synergistically increased PDGF-BB production 2-10-fold after 24 h. In contrast, when IFN-gamma was added to quiescent rat lung fibroblasts (RLFs) in the presence of PDGF-BB, the cytokine induced a concentration-dependent decrease in cell growth, while IFN-gamma alone did not affect proliferation. [I-125]PDGF-BB receptor assays showed that neither preincubation nor coincubation of RLF with IFN-gamma affected PDGF-BB binding to its receptors. C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 28 TC 18 Z9 18 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0929-7855 J9 J LIPID MEDIAT CELL JI J. Lipid Mediat. Cell Signal. PD JAN PY 1996 VL 13 IS 1 BP 89 EP 97 DI 10.1016/0929-7855(95)00048-8 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TQ981 UT WOS:A1996TQ98100008 PM 8821811 ER PT J AU Shinomiya, K Muto, M Kabasawa, Y Fales, HM Ito, Y AF Shinomiya, K Muto, M Kabasawa, Y Fales, HM Ito, Y TI Protein separation by improved cross-axis coil planet centrifuge with eccentric coil assemblies SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID COUNTERCURRENT CHROMATOGRAPHY; SYSTEMS AB The new prototype of the cross-axis coil planet centrifuge (X-axis CPC) fabricated in our laboratory provides various improvements over the original unit such as ambient temperature control, good visibility of the rotary frame and substantial reduction of the torque by a round transparent case, direct motor shaft coupling to the rotary frame to stabilize the system, and ease of belt tension adjustment using idler pulleys. The capability of the system was demonstrated in the separation of stable proteins with a polymer phase system using a pair of eccentric coil assembly separation columns. Cytochrome C, myoglobin and trypsinogen were well resolved and eluted in 5.5 h at a partition efficiency of 200 theoretical plates. The method provides a gentle environment for proteins without causing their deactivation or loss. C1 NIHON UNIV,SCI & TECHNOL RES INST,MACHINE SHOP,FUNABASHI,CHIBA 274,JAPAN. NHLBI,NIH,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP Shinomiya, K (reprint author), NIHON UNIV,COLL PHARM,7-7-1 NARASHINODAI,FUNABASHI,CHIBA 274,JAPAN. NR 5 TC 34 Z9 35 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1996 VL 19 IS 3 BP 415 EP 425 DI 10.1080/10826079608001225 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UD347 UT WOS:A1996UD34700007 ER PT J AU Du, QZ Shu, AM Ito, Y AF Du, QZ Shu, AM Ito, Y TI Purification of fish oil ethyl esters by high-speed countercurrent chromatography using non-aqueous solvent systems SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB High-speed countercurrent chromatography (HSCCC) was applied to purification of fish oil ethyl esters (FOEE). The CCC separations were performed using non-aqueous two-phase solvent systems in two steps: The first purification was carried out with a hexane-acetonitrile system where 30 mL of crude FOEE was cleaned in 140 min yielding 23.1 mL of refined FOEE. The product was colorless and free of saturated fatty acid esters. The second and final purification was performed with a hexane-dichloromethane-acetonitrile (5:1:4, v/v/v) where 1 g of the refined FOEE was resolved into three fractions, ethyl hexadecenoate, ethyl octadecenoate and the third composed of 56.4% of ethyl docosahexaenoate and 39.3% of ethyl eicosapentenoate. The separation was completed in 145 min. However, polyunsaturated fatty acids are not resolved with this solvent system due to their low partition coefficients. C1 NHLBI,BIOPHYS CHEM LAB,NIH,BETHESDA,MD 20892. RP Du, QZ (reprint author), CHINESE ACAD AGR SCI,TEA RES INST,HANGZHOU 310008,PEOPLES R CHINA. NR 5 TC 9 Z9 10 U1 1 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1996 VL 19 IS 9 BP 1451 EP 1457 DI 10.1080/10826079608007194 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UJ034 UT WOS:A1996UJ03400007 ER PT J AU Roilides, E Blake, C Holmes, A Pizzo, PA Walsh, TJ AF Roilides, E Blake, C Holmes, A Pizzo, PA Walsh, TJ TI Granulocyte-macrophage colony-stimulating factor and interferon-gamma prevent dexamethasone-induced immunosuppression of antifungal monocyte activity against Aspergillus fumigatus hyphae SO JOURNAL OF MEDICAL AND VETERINARY MYCOLOGY LA English DT Article ID FUNGICIDAL ACTIVITY; IFN-GAMMA; HYDROGEN-PEROXIDE; CUSHINGS-SYNDROME; GENE-EXPRESSION; RECOMBINANT; INVITRO; DAMAGE; NEUTROPHILS; INFECTIONS AB Treatment with corticosteroids is an important risk factor for development of invasive aspergillosis. We evaluated the effect of dexamethasone (DEX) on superoxide anion (O-2(-)) release and damage caused by elutriated human monocytes (EHM) on unopsonized hyphae of Aspergillus fumigatus. In addition, we studied the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on these functions of DEX-treated EHM. Treatment of EHM with concentrations of DEX ranging from 5 to 500 nM (1.4-140 ng ml(-1)) for 48 h suppressed O-2(-) release in response to phorbol myristate acetate in a dose-dependent fashion. Similarly, DEX significantly suppressed hyphal damage caused by EHM as measured by colorimetric MTT assay. Both GM-CSF (5 ng ml(-1)) and IFN-gamma (1.2 ng ml(-1)) added at day 0 to the EHM together with DEX (500 nM) significantly enhanced O-2(-) release and percentage hyphal damage, preventing the DEX-induced suppression of EHM function. Thus, GM-CSF and IFN-gamma prevented the deleterious effects of DEX on antifungal activity of EHM against Aspergillus suggesting a potential therapeutic role in patients at risk for or suffering from invasive aspergillosis. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NR 42 TC 60 Z9 65 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0268-1218 J9 J MED VET MYCOL JI J. Med. Vet. Mycol. PD JAN-FEB PY 1996 VL 34 IS 1 BP 63 EP 69 PG 7 WC Mycology SC Mycology GA UB625 UT WOS:A1996UB62500009 PM 8786473 ER PT J AU Kingston, HM Ledbetter, DH Tomlin, PI Gaunt, KL AF Kingston, HM Ledbetter, DH Tomlin, PI Gaunt, KL TI Miller-Dieker syndrome resulting from rearrangement of a familial chromosome 17 inversion detected by fluorescence in situ hybridisation SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE Miller-Dieker syndrome; fluorescence in situ hybridisation; chromosome 17 inversion ID SUBMICROSCOPIC DELETIONS; DISTAL 17Q; GENE; HYBRIDIZATION; DUPLICATION; 17P13 AB We report a case of Miller-Dieker syndrome (MDS) owing to an unbalanced rearrangement of a familial pericentric inversion of chromosome 17 (inv(17) (p13.3q25.1)). In addition to Lissencephaly and the facial features of MDS, the affected child had other congenital malformations consistent with distal 17q duplication. Initial cytogenetic analysis failed to show any abnormality and fluorescence in situ hybridisation (FISH) studies confirmed the 17p deletion in the proband and identified the chromosome 17 inversion in his mother. FISH studies were performed in other relatives and enabled first trimester prenatal diagnosis by chorionic villus sampling in a subsequent pregnancy of the proband's mother. These findings underline the value of FISH in the investigation of MDS families. C1 NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. ROYAL PRESTON HOSP,PAEDIAT NEUROL DEPT,PRESTON PR2 4HT,LANCS,ENGLAND. RP Kingston, HM (reprint author), ST MARYS HOSP,REG GENET SERV,HATHERSAGE RD,MANCHESTER M13 0JH,LANCS,ENGLAND. NR 29 TC 9 Z9 9 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JAN PY 1996 VL 33 IS 1 BP 69 EP 72 DI 10.1136/jmg.33.1.69 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TP217 UT WOS:A1996TP21700013 PM 8825053 ER PT J AU Takeda, K Yu, ZX Nishikawa, T Tanaka, M Hosoda, S Ferrans, VJ Kasajima, T AF Takeda, K Yu, ZX Nishikawa, T Tanaka, M Hosoda, S Ferrans, VJ Kasajima, T TI Apoptosis and DNA fragmentation in the bulbus cordis of the developing rat heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE apoptosis; mesenchymal cells; DNA fragmentation; phagocytosis; bulbus cordis; nick end labelling; cardiac morphogenesis ID CELL-DEATH AB Histologic, ultrastructural and nick end labeling studies were made of the process of apoptosis in the bulbus cordis of rat embryos. Apoptosis was observed between the 14th and 16th days of gestational age, at which time the bulbus cordis undergoes extensive remodeling. Three types of mesenchymal cells were identified in this region: cells undergoing apoptosis, cells engaging in the phagocytic removal of apoptotic cells, and cells not involved in either of these two processes. Fragmentation of DNA, demonstrated by nick end labeling, was found only in the apoptotic cells. The combined use of morphologic and labeling techniques is extremely useful in the evaluation of the contribution of apoptosis to cardiac morphogenesis. (C) 1996 Academic Press Limited C1 TOKYO WOMENS MED COLL, DEPT CARDIOL, SHINJUKU KU, TOKYO 162, JAPAN. NHLBI, PATHOL SECT, BETHESDA, MD 20892 USA. RP Takeda, K (reprint author), TOKYO WOMENS MED COLL, DEPT PATHOL, SHINJUKU KU, 8-1 KAWADA CHO, TOKYO 162, JAPAN. NR 12 TC 46 Z9 47 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JAN PY 1996 VL 28 IS 1 BP 209 EP 215 DI 10.1006/jmcc.1996.0020 PG 7 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA TP809 UT WOS:A1996TP80900020 PM 8745228 ER PT J AU Rivas, G Tangemann, K Minton, AP Engel, J AF Rivas, G Tangemann, K Minton, AP Engel, J TI Binding of fibrinogen to platelet integrin alpha IIb beta 3 in solution as monitored by tracer sedimentation equilibrium SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Article DE fibrinogen; integrin; binding; tracer sedimentation equilibrium ID GLYCOPROTEIN-IIB-IIIA; GPIIB-IIIA; MOLECULAR CHARACTERIZATION; CONSTITUENT GLYCOPROTEINS; ELECTRON-MICROSCOPY; RECEPTOR; MEMBRANE; COMPLEX; PROTEINS; LIGANDS AB Fibrinogen showed essentially no binding (K-D > 1 mM) to platelet alpha IIb beta 3 integrin in solution in the presence of Triton or octylglucoside above critical micellar concentrations, Under these conditions the integrin was an alpha beta monomer, After removal of the detergent from the Triton containing buffer (25 mM Tris/HCl;, 150 mM NaCl, 1 mM CaCl2, 1 mM MgCl2, pH 7.4) the integrin formed aggregates with hexamers as the most prominent species, as demonstrated by analytical ultracentrifugation and electron microscopy, Tracer sedimentation equilibrium experiments indicate that fibrinogen binds to the integrin aggregates, but with a surprisingly large K-D (at least 3 mu M). This value is 10- to 100-fold higher than values determined by solid phase assays or with integrins reconstituted onto lipid bilayers. C1 UNIV BASEL,BIOZENTRUM,CH-4003 BASEL,SWITZERLAND. NIDDKD,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. OI Rivas, German/0000-0003-3450-7478 NR 57 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD JAN-FEB PY 1996 VL 9 IS 1 BP 31 EP 38 DI 10.1002/(SICI)1099-1352(199601)9:1<31::AID-JMR237>3.3.CO;2-F PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UG955 UT WOS:A1996UG95500005 PM 8723317 ER PT J AU Dai, JR Hallock, YF Cardellina, JH Boyd, MR AF Dai, JR Hallock, YF Cardellina, JH Boyd, MR TI Vasculyne, a new cytotoxic acetylenic alcohol from the marine sponge Cribrochalina, vasculum SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID VACUUM LIQUID-CHROMATOGRAPHY; SEPARATION; MIXTURES AB A new C-43 acetylenic alcohol, vasculyne (1), was isolated by cytotoxicity-guided fractionation of the Caribbean sponge Cribrochalina vasculum. The structure of 1 was determined by spectroscopic methods. C1 NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAGNOSIS & CTR,FREDERICK,MD 21702. NR 11 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 1996 VL 59 IS 1 BP 88 EP 89 DI 10.1021/np9600199 PG 2 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA UR599 UT WOS:A1996UR59900022 PM 8984159 ER PT J AU Drake, CL Schwartz, PJ Turner, EH Rosenthal, NE AF Drake, CL Schwartz, PJ Turner, EH Rosenthal, NE TI Cognitive performance in seasonal affective disorder: Pattern recognition and the stroop task SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID ASSESSMENT BATTERY; DEPRESSION C1 NIMH,INTRAMURAL RES PROGRAM,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 21 TC 6 Z9 7 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 1996 VL 184 IS 1 BP 56 EP 59 DI 10.1097/00005053-199601000-00011 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TR860 UT WOS:A1996TR86000010 PM 8551292 ER PT J AU Kaelber, CT AF Kaelber, CT TI Psychiatric epidemiology: Assessment concepts and methods - Mezzich,JE, Jorge,MR, Salloum,IM SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP Kaelber, CT (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JAN PY 1996 VL 184 IS 1 BP 66 EP 66 DI 10.1097/00005053-199601000-00020 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TR860 UT WOS:A1996TR86000018 ER PT J AU Egan, MF Chrapusta, S Karoum, F Lipska, BK Wyatt, RJ AF Egan, MF Chrapusta, S Karoum, F Lipska, BK Wyatt, RJ TI Effects of chronic neuroleptic treatment on dopamine release: Insights from studies using 3-methoxytyramine SO JOURNAL OF NEURAL TRANSMISSION LA English DT Review DE neuroleptics; dopamine release; depolarization inactivation; 3-methoxytyramine; schizophrenia ID FREELY MOVING RATS; CHRONIC HALOPERIDOL TREATMENT; ATYPICAL ANTIPSYCHOTIC-DRUGS; MONOAMINE-OXIDASE INHIBITORS; NUCLEUS ACCUMBENS INVIVO; DECREASES BASAL DOPAMINE; MEDIAL PREFRONTAL CORTEX; TRANS-STRIATAL DIALYSIS; DEPOLARIZATION BLOCK; CHRONIC CLOZAPINE AB Antipsychotic medications appear to exert their therapeutic effects by blocking D2 receptors. While D2 blockade occurs rapidly, reduction in psychotic symptoms is often delayed. This time discrepancy has been attributed to the relatively slow development of depolarization inactivation (DI) of dopaminergic neurons. The reduced firing rates associated with DI has been hypothesized to reduce dopamine release and thus psychotic symptoms. Studies assessing changes in dopamine release during chronic neuroleptic treatment, using microdialysis and voltammetry, have been inconsistent. This may be due to methodological differences between studies, the invasive nature of these procedures, or other confounds. To investigate the effects of DI on dopamine release: 3-MT accumulation, an index of dopamine release that does not involve disruption of brain tissue: was measured during acute and chronic neuroleptic treatment. These results are compared with those using other techniques. 3-MT levels remained elevated after chronic treatment: suggesting that DI does not markedly reduce release. Regulation of dopamine release during DI was examined using two techniques known to block dopamine neuronal impulse flow. 3-MT levels were markedly reduced by both, implying that DI does not alter the portion of dopamine release mediated by neuronal impulse flow. Overall, studies to date suggest that the delayed therapeutic effects of neuroleptics are not due to reductions in impulse dependent dopamine release. Recent studies using a neurodevelopmental animal model of schizophrenia have pointed to altered pre- and post-synaptic indices of dopamine neurotransmission. The results suggest that neuroleptics may exert their therapeutic effects, in part, by limiting the fluctuations in dopamine release, and raise new issues for future research. RP Egan, MF (reprint author), NIMH,CTR RES NEUROSCI,CLIN BRAIN DISORDERS BRANCH,2700 M L KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 139 TC 14 Z9 14 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 1996 VL 103 IS 7 BP 777 EP 805 DI 10.1007/BF01273358 PG 29 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UZ999 UT WOS:A1996UZ99900002 PM 8872864 ER PT J AU Yasar, S Goldberg, JP Goldberg, SR AF Yasar, S Goldberg, JP Goldberg, SR TI Are metabolites of 1-deprenyl (selegiline) useful or harmful? Indications from preclinical research SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article ID L-DEPRENYL SELEGILINE; MONOAMINE-OXIDASE INHIBITORS; ABUSE LIABILITY; STIMULANT-DRUGS; DOPAMINE UPTAKE; B INHIBITOR; D-ISOMERS; AMPHETAMINE; RATS; METHAMPHETAMINE AB A frequent topic of controversy has been whether metabolism of l-deprenyl (selegiline) to active metabolites is a detriment to clinical use. This paper reviews possible roles of the metabolites of l-deprenyl in producing unwanted adverse side effects or in augmenting or mediating its clinically useful actions. Levels of l-amphetamine and l-methamphetamine likely to be reached, even with excessive intake of l-deprenyl, would be unlikely to produce neurotoxicity and there is no preclinical or clinical evidence of abuse liability of l-deprenyl. In contrast, there is evidence that l-amphetamine and 1-methamphetamine have some qualitatively different actions than their disomer counterparts on EEG and cognitive functioning which might result in beneficial clinical effects and complement beneficial clinical actions of 1-deprenyl itself. C1 NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,NIH,BEHAV PHARMACOL & GENET SECT,DIV INTRAMURAL RES,BALTIMORE,MD 21224. VISTA HILL HOSP,CHULA VISTA,CA. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NR 50 TC 29 Z9 31 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 1996 IS 48 BP 61 EP 73 PG 13 WC Neurosciences SC Neurosciences & Neurology GA VX963 UT WOS:A1996VX96300008 ER PT J AU Finberg, JPM Lamensdorf, I Commissiong, JW Youdim, MBH AF Finberg, JPM Lamensdorf, I Commissiong, JW Youdim, MBH TI Pharmacology and neuroprotective properties of rasagiline SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article ID MONOAMINE-OXIDASE INHIBITORS; L-DOPA; RAT STRIATUM; HUMAN-BRAIN; METABOLISM; DEPRENYL; NEURONS; SURVIVAL; DEATH AB Rasagiline [R(+)-N-propargyl-1-aminoindane] is a selective irreversible inhibitor of MAO-B which is not metabolised to amphetamine-like derivatives. Like deprenyl, when given to rats in a dose selective for inhibition of MAO-B, it does not affect striatal extracellular fluid dopamine levels, but when administered chronically (21 days) it increased striatal microdialysate dopamine without reduction in deaminated metabolites. Similarly to deprenyl, rasagiline (10(-6)M) increased the percentage of tyrosine hydroxylase positive cells in a primary culture of rat fetal mesencephalic cells (6 days in culture). Rasagiline, but not deprenyl, also increased the number of neurons per held in this organotypic culture. C1 NINCDS,NIH,BETHESDA,MD 20892. TECHNION ISRAEL INST TECHNOL,RAPPAPORT FAMILY INST RES MED SCI,IL-31096 HAIFA,ISRAEL. RP Finberg, JPM (reprint author), TECHNION ISRAEL INST TECHNOL,BRUCE RAPPAPORT FAC MED,PHARMACOL UNIT,POB 9649,IL-31096 HAIFA,ISRAEL. NR 29 TC 72 Z9 73 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 1996 IS 48 BP 95 EP 101 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VX963 UT WOS:A1996VX96300011 PM 8988465 ER PT J AU Brown, P AF Brown, P TI Transmissible cerebral amyloidosis SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article; Proceedings Paper CT 4th International Symposium of the Research Initiative EBEWE CY OCT 13-15, 1995 CL VIENNA, AUSTRIA ID CREUTZFELDT-JAKOB-DISEASE; STRAUSSLER-SCHEINKER DISEASE; PRION PROTEIN GENE; FATAL FAMILIAL INSOMNIA; PERSON TRANSMISSION; GERSTMANN; MUTATION; LINKAGE AB Transmissible cerebral amyloidosis occurs in three forms - sporadic, iatrogenic, and familial. Clinical and epidemiological aspects of sporadic disease are briefly described, followed by an up-to-date review of the increasing numbers and varieties of iatrogenic and mutation-positive familial cases. RP Brown, P (reprint author), NINCDS,CNS STUDIES LAB,NIH,BLDG 36,ROOM 5B21,BETHESDA,MD 20892, USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 1996 IS 47 BP 219 EP 229 PG 11 WC Neurosciences SC Neurosciences & Neurology GA UZ461 UT WOS:A1996UZ46100016 ER PT J AU Lin, PX Kusano, K Zhang, QL Felder, CC Geiger, PM Mahan, LC AF Lin, PX Kusano, K Zhang, QL Felder, CC Geiger, PM Mahan, LC TI GABA(A) receptors modulate early spontaneous excitatory activity in differentiating P19 neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE GABA(A) receptor; neuronal differentiation; PCR; embryonal carcinoma; cell line; GABA ID EMBRYONAL CARCINOMA-CELLS; SUBUNIT MESSENGER-RNAS; CENTRAL-NERVOUS-SYSTEM; RAT SPINAL-CORD; POSTNATAL-DEVELOPMENT; EXPRESSION; NEUROTRANSMITTERS; SIGNALS; CALCIUM; LINE AB P19 embryonic carcinoma (EC) stem cells are pluripotent and are efficiently induced to differentiate into neurons and glia with retinoic acid (RA) treatment. Within 5 days, a substantial number of differentiating P19 cells express gene products that are characteristic of a neuronal phenotype. P19 neurons were used as a model to explore the relationship between neuronal ''differentiation'' in vitro and the acquisition of gamma-aminobutyric acid (GABA(A)) receptors and functional GABA responses. Pulse-labeling experiments using bromodeoxyuridine indicated that all neurons had become postmitotic within 3-4 days after treatment with RA. This was confirmed by a reduction in the immunocytochemical detection of the undifferentiated stem cell antigen SSEA-1. Subsequently, a transient expression of nestin was observed during the first 5 days in vitro (DIV) after exposure to RA. By 5-10 DIV after RA, a significant number of neurons (similar to 80-90%) expressed immunocytochemically detectable glutamate decarboxylase and GABA coincident with the acquisition of membrane binding sites for tetanus toxin. These phenotypic markers were maintained for >30 DIV after RA. Under current-clamp conditions, random, low-amplitude, spontaneous electrical activity appeared in neurons within the first few days after RA treatment and this was blocked by the specific GABA(A) receptor antagonist bicuculline. Thereafter, the appearance and progressive increases in the frequency of spontaneous action potentials in P19 neurons were observed that were similarly attenuated by bicuculline. In neurons > 5 DIV after RA, exogenous application of GABA elicited similar action potentials, The onset of excitatory responses to GABA or muscimol in voltage-clamped neurons appeared immediately after the cessation of neuronal mitosis and before the previously reported acquisition of responses to glutamate. In fura-e imaging studies, the exogenous application of GABA resulted in neuron-specific increases in intracellular Ca2+. Thus, P19 neurons provide an in vitro model for the study of the early acquisition and properties of electrical excitability to GABA and the expression of functional GABA(A) receptors. C1 NINCDS,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD. RP Lin, PX (reprint author), NINCDS,NEUROCHEM LAB,BLDG 36,ROOM 4D20,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 42 Z9 42 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 1996 VL 66 IS 1 BP 233 EP 242 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TK603 UT WOS:A1996TK60300030 PM 8522959 ER PT J AU Sei, Y Paul, IA Saito, K Layar, R Hartley, JW Morse, HC Skolnick, P Heyes, MP AF Sei, Y Paul, IA Saito, K Layar, R Hartley, JW Morse, HC Skolnick, P Heyes, MP TI Quinolinic acid levels in a murine retrovirus-induced immunodeficiency syndrome SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE LP-BM5 murine leukemia virus; zidovudine; azidothymidine; brain; blood; macrophages; quinolinic acid ID CEREBROSPINAL-FLUID; IMMUNE ACTIVATION; LEUKEMIA VIRUSES; COAT PROTEIN; L-TRYPTOPHAN; BRAIN; AIDS; DISEASE; HIV-1; CELLS AB Mice infected with the retrovirus mixture designated LP-BM5 murine leukemia virus (MuLV) develop an immunosuppressive disease, Quinolinic acid (QUIN) is an endogenous neurotoxic N-methyl-D-aspartate agonist that may contribute to the pathogenesis of HIV-associated neurologic disease. In the present study, the levels of QUIN in brain and blood were measured in mice infected with LP-BM5 MuLV and compared with those in uninfected mice and mice infected with the nonpathogenic strain of ecotropic MuLV (helper component of LP-BM5 MuLV). Infection with LP-BM5 MuLV resulted in progressive increases in blood QUIN levels beginning 2 weeks after inoculation that peaked by 16 weeks postinfection. QUIN levels were also increased in cerebral cortex, hippocampus, and striatum. In systemic tissues, QUIN levels were increased in lung, liver, and spleen. In contrast, infection with the ecotropic viral component of the LP-BM5 MuLV mixture was not associated with any changes in brain, blood, or systemic tissue QUIN levels, even though helper virus burdens were comparable to those in mice infected with LP-BM5 MuLV. Treatment of LP-BM5 MuLV-infected mice with the antiretroviral agent zidovudine (azidothymidine) significantly reduced blood and brain QUIN levels in association with reductions in viral load in brain and spleen. These observations suggest that elevated QUIN production is not attributable to productive infection with retrovirus per se but occurs in response to an agent or agents, such as cytokines, that are produced by the host in response to virus infection. C1 NIMH,ANALYT BIOCHEM SECT,CLIN SCI LAB,BETHESDA,MD 20892. NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. OI Morse, Herbert/0000-0002-9331-3705 NR 45 TC 33 Z9 33 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 1996 VL 66 IS 1 BP 296 EP 302 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TK603 UT WOS:A1996TK60300037 PM 8522967 ER PT J AU Yu, OF Chuang, DM AF Yu, OF Chuang, DM TI Inhibition of excitatory amino acid-induced phosphoinositide hydrolysis as a possible mechanism of nitroprusside neurotoxicity SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE nitroprusside; nitric oxide donors; phosphoinositide hydrolysis; quisqualate; kainate; NMDA; glutamate; neurotoxicity ID CEREBELLAR GRANULE CELLS; GLUTAMATE-RECEPTOR AGONISTS; CYCLIC-GMP PRODUCTION; BDNF MESSENGER-RNA; NITRIC-OXIDE; SODIUM-NITROPRUSSIDE; PRIMARY CULTURES; CALCIUM INFLUX; NMDA RECEPTORS; NEUROTROPHIC FACTOR AB Inclusion of sodium nitroprusside {Na-2[Fe2+(CN)(5)NO]} into the culture medium is toxic to cultured rat cerebellar granule neurons. A possible underlying mechanism may be the inhibition of phosphoinositide (PI) response to excitatory amino acids (EAAs) because activation of glutamate receptors can be neuroprotective and neurotrophic in differentiating neurons. Sodium nitroprusside selectively inhibited the PI response to EAAs (NMDA > glutamate = quisqualate > kainate) without affecting that to carbachol or KCl. In contrast, S-nitroso-N-acetyl-penicillamine (SNAP), another nitric oxide (NO) donor, potentiated NRSDA-induced PI hydrolysis. Hemoglobin reversed the effects of nitroprusside and SNAP. However, NO may not be involved because NO solution was without effect and N-acetylpeniciilamine, a SNAP analogue that does not contain a NO moiety, also potentiated NMDA-induced PI hydrolysis in a hemoglobin-sensitive manner, Furthermore, the metabolites of NO (nitrate and nitrite), L-arginine, reduced glutathione, 8-bromo-cyclic guanosine 3':5'-cyclic monophosphate (8-Br-cGMP), and atrial natriuretic peptide, which accelerates the production of cGMP independent of NO, were ineffective as modulators. However, potassium ferrocyanide {K-4[Fe2+(CN)(6)]}, but not potassium ferricyanide {K-3[Fe-3+(CM)(6)]}, inhibited NMDA-induced PI hydrolysis as effectively as nitroprusside, but this inhibition was not reversed by hemoglobin. Cyanide, a product from the disintegration of nitroprusside, potentiated rather than inhibited NMDA-induced PI hydrolysis. Taken together, these results suggest that the parent molecule itself, nitroprusside, contributes primarily in inhibiting EAA-induced PI hydrolysis. Inhibition dEAA-induced PI hydrolysis may in part mediate the mechanisms of nitroprusside toxicity in primary cultures of differentiating cerebellar granule neurons. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,WASHINGTON,DC 20032. NR 62 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 1996 VL 66 IS 1 BP 346 EP 354 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TK603 UT WOS:A1996TK60300043 PM 8522973 ER PT J AU Nishida, K Markey, SP Kustova, Y Morse, HC Skolnick, P Basile, AS Sei, Y AF Nishida, K Markey, SP Kustova, Y Morse, HC Skolnick, P Basile, AS Sei, Y TI Increased brain levels of platelet-activating factor in a murine acquired immune deficiency syndrome are NMDA receptor-mediated SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE AIDS; LP-BM5 murine leukemia virus; brain; encephalopathy; platelet-activating factor ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; MODEL; CELLS; AIDS AB Mice infected with the LP-BM5 murine leukemia virus (MuLV) develop an immunodeficiency syndrome (murine AIDS) and an encephalopathy characterized by impaired spatial learning and memory. Because platelet-activating factor (PAF) has been implicated in the pathogenesis of HIV-associated dementia complex, brain PAF levels were measured in LP-BM5 MuLV-infected mice. PAF levels in cerebral cortex and hippocampus were significantly increased at 6 and 12 weeks after LP-BM5 MuLV inoculation, whereas significant increases in striatal and cerebellar PAF levels were observed only at 12 weeks after inoculation. Administration of the NMDA antagonist MK-801 significantly reduced the increased PAF levels in the cerebral cortex and hippocampus of LP-BM5 MuLV-infected mice. These results indicate that the LP-BM5 MuLV-induced increases in brain PAF levels are the result of NMDA receptor activation and are consistent with the hypothesis that elevated CNS PAF levels contribute to the behavioral deficits observed in LP-BM5 MuLV-infected mice. C1 NIDDKD, NEUROSCI LAB, BETHESDA, MD 20892 USA. NIMH, CLIN SCI LAB, ANALYT BIOCHEM SECT, BETHESDA, MD 20892 USA. NIAID, IMMUNOPATHOL LAB, BETHESDA, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 NR 19 TC 41 Z9 43 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JAN PY 1996 VL 66 IS 1 BP 433 EP 435 PG 3 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TK603 UT WOS:A1996TK60300055 PM 8522986 ER PT J AU Acevedo, LD Holloway, HW Rapoport, SI Shetty, HU AF Acevedo, LD Holloway, HW Rapoport, SI Shetty, HU TI Increased uptake of myo-inositol in cortical neurons from the trisomy 16 mouse SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S14 EP S14 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200056 ER PT J AU Amin, ND Pant, AC Veeranna Pant, HC AF Amin, ND Pant, AC Veeranna Pant, HC TI Expression of a human neurofilament (NF-H), KSPXK multiple repeat peptide and its phosphorylation by neuronal CDK5. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,LNC,NIH,BETHESDA,MD 20892. NHLBI,LBG,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S65 EP S65 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200257 ER PT J AU Araki, T Taniwaki, T Becerra, SP Chader, GJ Hirashima, N Etcheberrigaray, R Schwartz, JP AF Araki, T Taniwaki, T Becerra, SP Chader, GJ Hirashima, N Etcheberrigaray, R Schwartz, JP TI Pigment epithelium-derived factor (PEDF) protects cerebellar granule cells against glutamate toxicity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,NIH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NEI,NIH,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NINCDS,NIH,ADAPT SYST LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S13 EP S13 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200050 ER PT J AU Armstrong, RC Kim, JG Hudson, LD AF Armstrong, RC Kim, JG Hudson, LD TI Differential expression of proteins of the CCHC class of ''zinc finger'' DNA-binding proteins SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S19 EP S19 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200075 ER PT J AU Cadet, JL AF Cadet, JL TI BCL2 protects against methamphetamine induced neurotoxicity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIDA,MOL NEUROPSYCHIAT SECT,NIH,IRP,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 2 BP S111 EP S111 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UN209 UT WOS:A1996UN20900444 ER PT J AU Chang, MC Rabin, O Grange, E Hayakawa, T Bell, J AF Chang, MC Rabin, O Grange, E Hayakawa, T Bell, J TI Intravenous injection of [9,10-H-3]stearate to examine brain lipid metabolism in awake rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S46 EP S46 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200181 ER PT J AU Deutsch, J Rapoport, SI Purdon, AD AF Deutsch, J Rapoport, SI Purdon, AD TI Comparison of unesterified fatty acid and acyl-CoA changes in brain during decapitation-ischemia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S94 EP S94 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200376 ER PT J AU Dienel, GA Wang, RY Cruz, NF AF Dienel, GA Wang, RY Cruz, NF TI Fate of glucose during ''aerobic glycolysis'': Increased flux into brain glycogen after sensory stimulation SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S95 EP S95 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200377 ER PT J AU Donovan, M Hahn, R Tessorollo, L Hempstead, BL AF Donovan, M Hahn, R Tessorollo, L Hempstead, BL TI Neurotrophin 3 is essential for mammalian cardiac development SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 CHILDRENS HOSP,BOSTON,MA. CORNELL UNIV MED COLL,NEW YORK,NY. NCI,FREDERICK,MD 21701. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 2 BP S6 EP S6 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UN209 UT WOS:A1996UN20900024 ER PT J AU Dosemeci, A AF Dosemeci, A TI Role of CaM kinase II in synaptic modification: A historical perspective. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,NIH,NEUROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S31 EP S31 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200123 ER PT J AU Farrer, RG Quarles, RH AF Farrer, RG Quarles, RH TI A sulfated ganglioside expressed by oligodendrocyte progenitors is the most reactive glycolipid antigen for the A2B5 antibody SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,NIH,MYELIN & BRAIN DEV SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S37 EP S37 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200147 ER PT J AU Goldberg, SR Yasar, S AF Goldberg, SR Yasar, S TI Methamphetamine administration and associated neurotoxicity: Effects of l-deprenyl (selegiline). SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIDA,NIH,DIR,PRECLIN PHARMACOL LAB,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 2 BP S20 EP S20 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UN209 UT WOS:A1996UN20900078 ER PT J AU Horinaka, N Pak, H Jehle, J Kennedy, C Sokoloff, L AF Horinaka, N Pak, H Jehle, J Kennedy, C Sokoloff, L TI Effect of intravenous caffeine injection on cerebral blood flow response to hypoglycemia. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S95 EP S95 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200378 ER PT J AU Jones, CR Arai, T Bell, J Rapoport, SI AF Jones, CR Arai, T Bell, J Rapoport, SI TI Effect of cholinergic stimulation on synaptic incorporation of radiolabeled plasma arachidonic and palmitic acid in rat brain. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S47 EP S47 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200187 ER PT J AU Kawai, N McCarron, RM Spatz, M AF Kawai, N McCarron, RM Spatz, M TI Effect of endothelin and hypoxia on brain capillary Na+-K+-Cl cotransport activity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,NIH,STROKE BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S99 EP S99 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200396 ER PT J AU McCall, M Gregg, R Behringer, RR Brenner, M Zheng, CL Pearce, RA Chiu, SY Delaney, CL Messing, A AF McCall, M Gregg, R Behringer, RR Brenner, M Zheng, CL Pearce, RA Chiu, SY Delaney, CL Messing, A TI Targeted deletion in astrocyte intermediate filament (GFAP) alters neuronal physiology SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S75 EP S75 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200297 ER PT J AU Nussenblatt, R AF Nussenblatt, R TI Mechanisms of intraocular inflammatory disease and possible interventions SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NEI,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S54 EP S54 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200214 ER PT J AU Quarles, RH Farrer, RG Yim, SH AF Quarles, RH Farrer, RG Yim, SH TI Gangliosides in the differentiation of oligodendrocytes SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,NIH,MYELIN & BRAIN DEV SECT,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S97 EP S97 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200387 ER PT J AU Rabin, O Grange, E Deutsch, J Chang, MCJ Rapoport, SI Purdon, AD AF Rabin, O Grange, E Deutsch, J Chang, MCJ Rapoport, SI Purdon, AD TI Brain acyl-CoA concentrations in ischemia reperfusion. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S98 EP S98 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200389 ER PT J AU Rapoport, SI Chandrasekaran, K Brady, DR Hatanpaa, K AF Rapoport, SI Chandrasekaran, K Brady, DR Hatanpaa, K TI Brain oxidative metabolism in Alzheimer disease (AD). SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S74 EP S74 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200293 ER PT J AU Ricketts, MH Goldman, D Long, JC Manowitz, P AF Ricketts, MH Goldman, D Long, JC Manowitz, P TI Arylsulfatase A pseudodeficiency associated mutations: Population studies and identification of a novel haplotype SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,PISCATAWAY,NJ 08854. NIAAA,BETHESDA,MD 20205. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S91 EP S91 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200363 ER PT J AU Sasagasako, N Quarles, TH AF Sasagasako, N Quarles, TH TI Myelin gene expression in immortalized S16 Schwann cells is stimulated by plasma membrane fractions from these cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,NIH,MOLEC & CELLULAR NEUROBIOL LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S49 EP S49 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200194 ER PT J AU Sokoloff, L AF Sokoloff, L TI Quantitative determination of cerebral blood flow and energy metabolism SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S72 EP S72 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200286 ER PT J AU South, SA Deibler, GE DeVries, GH AF South, SA Deibler, GE DeVries, GH TI The mitogenic effect of myelin basic protein is mediated by calcium and cell surface receptors. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 LOYOLA UNIV,MED CTR,DEPT CELL BIOL NEUROBIOL & ANAT,MAYWOOD,IL 60153. NIMH,NIH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S22 EP S22 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200087 ER PT J AU Spatz, M McCarron, RM AF Spatz, M McCarron, RM TI The role of endothelin-1 in human cerebromicrovascular endothelium SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 2 BP S108 EP S108 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UN209 UT WOS:A1996UN20900432 ER PT J AU Stebbins, JW Jaffe, H Fales, HM Moller, JR AF Stebbins, JW Jaffe, H Fales, HM Moller, JR TI Determination of the carboxy-terminus of a proteolysis product derived from myelin-associated glycoprotein (dMAG) SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,DEMYELINATING DISORDERS UNIT,LMCN,BETHESDA,MD 20892. NINCDS,LNC,PROT PEPTIDE SEQUENCING FACIL,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S5 EP S5 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200019 ER PT J AU Suchy, SF Nussbaum, RL AF Suchy, SF Nussbaum, RL TI A defective phosphatidylinositol 4,5-bisphosphate 5-phosphatase is responsible for the oculocerebrorenal syndrome of Lowe. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S45 EP S45 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200180 ER PT J AU Veeranna Shetty, KT Amin, N Jaffe, H Pant, HC AF Veeranna Shetty, KT Amin, N Jaffe, H Pant, HC TI A multimeric kinase-cytoskeletal complex associates with Munc-18/P67 in rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S64 EP S64 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200256 ER PT J AU Warrington, AE Wiese, C Hudson, LD AF Warrington, AE Wiese, C Hudson, LD TI Inactivation of the myelin transcription factor, MyTl SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,NIH,LAB DEV NEUROGENET,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S18 EP S18 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200072 ER PT J AU Williams, WM Chang, MCJ Grange, E Rapoport, SI AF Williams, WM Chang, MCJ Grange, E Rapoport, SI TI Incorporation of radiolabeled arachidonate and palmitate into rat brain microvessels SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S44 EP S44 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200176 ER PT J AU Yim, SH Quarles, RH AF Yim, SH Quarles, RH TI MAP kinase activation by growth factors in O-2A lineage cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINCDS,MYELIN & BRAIN DEV SECT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1996 VL 66 SU 1 BP S67 EP S67 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TY002 UT WOS:A1996TY00200267 ER PT J AU Fukuhara, K Kvetnansky, R Weise, VK Ohara, H Yoneda, R Goldstein, DS Kopin, IJ AF Fukuhara, K Kvetnansky, R Weise, VK Ohara, H Yoneda, R Goldstein, DS Kopin, IJ TI Effects of continuous and intermittent cold (SART) stress on sympathoadrenal system activity in rats SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE SART stress; cold stress; plasma catecholamines; plasma catecholamine metabolites; tyrosine hydroxylase activity ID PLASMA-CATECHOLAMINE RESPONSES; TYROSINE-HYDROXYLASE ACTIVITY; PHYSIOLOGICAL SIGNIFICANCE; NOREPINEPHRINE TURNOVER; ADRENAL-MEDULLA; BLOOD-PRESSURE; EXPOSURE; MICE; 3,4-DIHYDROXYPHENYLALANINE; IMMOBILIZATION AB We compared sympathoadrenal responses to intermittent cold (SART) stress (in which cold exposure is interrupted by 4-hourly intervals daily at room temperature) with those to continuous cold (-3 degrees C) stress. Plasma levels of dihydroxyphenylalanine (DOPA), catecholamines and their metabolites as well as tyrosine hydroxylase (TH) activities in sympathetically innervated tissues were examined in rats exposed to each stressor for 1 day or for 5 days. Neither SART nor continuous exposure to cold for 1 day or 5 days altered plasma epinephrine (EPI) levels, However, norepinephrine (NE) and dihydroxyphenylglycol (DHPG) levels increased markedly during exposure to these stressors. On the first day of SART or continuous cold stress, NE levels were increased similarly, but the increments in DHPG levels were greater during SART stress, Since DHPG is formed in neurons, neural reuptake of NE may be more enhanced on the first day of SART stress than on the first day of continuous cold stress. After 5 days of SART stress plasma NE levels were significantly higher than those found after 5 days of continuous cold exposure. Plasma levels of DHPG were elevated to the same extent in both 5 days SART- and continuously cold-stressed rats, whereas plasma levels of methoxyhydroxyphenylglycol (MHPG) increased only by 5 days SART stress. Even at 1 h after the removal from 5 days SART stress, increased plasma levels of NE, DHPG and MHPG were still evident, These results suggest that 5 days SART stress elevates extraneuronal O-methylation of DHPG, and that NE turnover is more greatly increased by SART stress than by continuous cold stress, Plasma levels of DOPA, dopamine, dihydroxyphenylacetic acid and homovanillic acid also increased after either SART or continuous cold stress for 1 day and 5 days. Adrenal TH activities were significantly increased in rats exposed to SART or continuous cold stress for 1 day and 5 days, but in brown fat TH activity was elevated only in rats exposed to 5 days of continuous cold, Both SART and continuous cold stress are selective and potent stimuli for activation of the sympathoneural system, apparently without significant adrenomedullary EPI release, The increase of TH activity in the brown fat pad as well as of plasma NE and its metabolites is probably a result of adaptation to cold. It appears that even short intervals of return to a normal environmental temperature, as in SART, are sufficient to diminish sympathetic adaptation to cold. C1 SLOVAK ACAD SCI,INST EXPTL ENDOCRINOL,BRATISLAVA 83306,SLOVAKIA. NINCDS,NIH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP Fukuhara, K (reprint author), NIPPON ZOKI PHARMACEUT CO LTD,INST BIOACT SCI,DEPT PHARMACOL 1,YASHIRO,HYOGO 67314,JAPAN. NR 51 TC 30 Z9 31 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JAN PY 1996 VL 8 IS 1 BP 65 EP 72 DI 10.1111/j.1365-2826.1996.tb00687.x PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA TW090 UT WOS:A1996TW09000008 PM 8932738 ER PT J AU Litvan, I Hauw, JJ Bartko, JJ Lantos, PL Daniel, SE Horoupian, DS McKee, A Dickson, D Bancher, C Tabaton, M Jellinger, K Anderson, DW AF Litvan, I Hauw, JJ Bartko, JJ Lantos, PL Daniel, SE Horoupian, DS McKee, A Dickson, D Bancher, C Tabaton, M Jellinger, K Anderson, DW TI Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE neuropathology; Pick's disease; postencephalitic parkinsonism; progressive supranuclear palsy; reliability; validity ID ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; POSTENCEPHALITIC PARKINSONISM; SENILE DEMENTIA; DEGENERATION; DIAGNOSIS AB We investigated the validity and reliability of diagnoses made by eight neuropathologists who used the preliminary NINDS neuropathologic diagnostic criteria for progressive supranuclear palsy (PSP) and related disorders. The specific disorders were typical, atypical, and combined PSP, postencephalitic parkinsonism, corticobasal ganglionic degeneration, and Pick's disease. These disorders were chosen because of the difficulties in their neuropathologic differentiation. We assessed validity by measuring sensitivity and positive predictive value. Reliability was evaluated by measuring pairwise and group agreement. From a total of 62 histologic cases, each neuropathologist independently classified 16 to 19 cases for the pairwise analysis and 5 to 6 cases for the group analysis. The neuropathologists were unaware of the study design, unfamiliar with the assigned cases, and initially had no clinical information about the cases. Our results showed that with routine sampling and staining methods, neuropathologic examination alone was not fully adequate for differentiating the disorders. The main difficulties were discriminating the subtypes of PSP and separating postencephalitic parkinsonism from PSP. Corticobasal ganglionic degeneration and Pick's disease were less difficult to distinguish from PSP. The addition of minimal clinical information contributed to the accuracy of the diagnosis. On the basis of results obtained, we propose clinicopathologic diagnostic criteria to improve on the NINDS criteria. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. HOP LA PITIE SALPETRIERE,ASSOC CLAUDE BERNARD,INSERM U360,RAYMOND ESCOUROLLE NEUROPATHOL LAB,PARIS,FRANCE. NIMH,DIV EPIDEMIOL & RES STUDIES,BETHESDA,MD 20892. INST PSYCHIAT,DEPT NEUROPATHOL,LONDON SE5 8AF,ENGLAND. INST NEUROL,DEPT NEUROPATHOL,LONDON WC1N 3BG,ENGLAND. INST NEUROL,PARKINSONS DIS SOC BRAIN TISSUE BANK,LONDON WC1N 3BG,ENGLAND. STANFORD UNIV,SCH MED,DEPT PATHOL NEUROPATHOL,STANFORD,CA 94305. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. ALBERT EINSTEIN COLL MED,DEPT NEUROPATHOL,BRONX,NY. LAINZ HOSP,LUDWIG BOLTZMANN INST CLIN NEUROBIOL,A-1130 VIENNA,AUSTRIA. CASE WESTERN RESERVE UNIV,DIV NEUROPATHOL,CLEVELAND,OH 44106. RP Litvan, I (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Dickson, Dennis W/0000-0001-7189-7917; Litvan, Irene/0000-0002-3485-3445 NR 39 TC 289 Z9 295 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 1996 VL 55 IS 1 BP 97 EP 105 DI 10.1097/00005072-199601000-00010 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA TP445 UT WOS:A1996TP44500010 PM 8558176 ER PT J AU McClurkin, JW Optican, LM AF McClurkin, JW Optican, LM TI Primate striate and prestriate cortical neurons during discrimination .1. Simultaneous temporal encoding of information about color and pattern SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PRIMARY VISUAL-CORTEX; TWO-DIMENSIONAL PATTERNS; STATE DEPENDENT ACTIVITY; SACCADIC EYE-MOVEMENTS; SINGLE UNITS; SPIKE TRAINS; ORIENTATION SELECTIVITY; TRANSMITTED INFORMATION; 2-DIMENSIONAL PATTERNS; FUNCTIONAL-ANATOMY AB 1. We recorded the responses of neurons in cortical areas V1, V2, and V4 to a set of 36 colored patterns while monkeys discriminated among the stimuli on the basis of their color or their pattern. In the discrimination task a colored square or a black and white pattern was presented foveally as a cue stimulus. The monkey was required to choose, by making a saccade, which of three peripheral targets had the same property as the cue. One of the peripheral targets was centered on the receptive field of the neuron, and the other two were positioned at equally distant points around the circumference of an imaginary circle centered on the cue and passing through the receptive field. 2. An examination of the responses to the stimuli showed that there was a complex interaction between the effects of color and of pattern on the neuronal responses. Because of these interactions, we tested sensitivity to color and pattern by sorting the responses to all stimuli according to the color or pattern of the stimulus. We found that the number of spikes in the responses was affected by only one or the other of the stimulus parameters, but that the temporal distribution of spikes was affected by both stimulus parameters. We quantified the relative sensitivities of each neuron to color and pattern by dividing the amount of information the neuron transmitted about color by the amount of information the neuron transmitted about pattern. The distributions of information ratios assuming a spike count code were broad, indicating that many neurons were sensitive to only one stimulus parameter or the other. In contrast, the distributions of information ratios assuming a waveform code were narrow and centered near 1.0, indicating nearly equal sensitivities to both stimulus parameters. 3. In our initial experiments, it appeared that the color or pattern used as the cue for the discrimination task affected the responses of many neurons to stimuli on the receptive field. To determine whether the cue effect was due to simple visual interactions or to the cognitive requirements of the discrimination task, we performed a control experiment in which the cue was turned on 80 ms after the peripheral stimuli. For many of the neurons in the control experiment, an effect related to the cue appeared in the response before the cue had been turned on. Thus the effect we observed must have been due to visual interactions with the distracter targets, even though these were outside the neuron's classically defined receptive field. 4. We compared the rate at which color and pattern information developed in the response over time assuming either a spike count or a waveform code. The spike count code gained more of its information in the first 20 ms of the response than did the waveform code, but thereafter the information carried by the spike count code developed more slowly and reached a lower asymptote than did the information carried by the waveform code. 5. The waveform codes carried nearly equal amounts of information about color and pattern, but the messages about these two parameters did not develop at the same rate in all areas. The messages about color and pattern developed at the same rate in area V1, but messages about color developed more slowly than did the messages about pattern in areas V2 and V4. 6. These results offer a neurophysiological basis for both the psychological separateness of color and pattern, and the binding of color and pattern into a unified percept. We propose that the separateness of color and form arises not by virtue of their being encoded by different populations of neurons, but by virtue of their being encoded by separable waveform codes in the responses of single neurons, We propose that the binding of color and form occurs by virtue of their codes being multiplexed on the same neurons. RP McClurkin, JW (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 49,RM 2A50,49 CONVENT DR MSC 4435,BETHESDA,MD 20892, USA. NR 55 TC 26 Z9 26 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 1996 VL 75 IS 1 BP 481 EP 495 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA TT526 UT WOS:A1996TT52600036 PM 8822572 ER PT J AU McClurkin, JW Zarbock, JA Optican, LM AF McClurkin, JW Zarbock, JA Optican, LM TI Primate striate and prestriate cortical neurons during discrimination .2. Separable temporal codes for color and pattern SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ORIENTATION SELECTIVITY; CHROMATIC MECHANISMS; FUNCTIONAL-ANATOMY; CORTEX; MACAQUE; MONKEY; FORM; PERCEPTION; VISION; SEGREGATION AB 1. In the previous paper we reported our analysis of the responses of neurons in cortical areas V1, V2, and V4 to a set of stimuli that consisted of all 36 combinations of six colors and six patterns. Neurons in all three cortical areas simultaneously encoded information about both the color and pattern of the stimulus in the number and temporal distribution of spikes in their responses. To account for this ability, we propose that a neuron's response consists of separable temporal codes representing the color and pattern of the stimulus that are multiplexed together. 2. We used nonlinear regression to fit the model parameters to the data. We used the responses to 30 of the 36 stimuli as a training set to estimate the parameters of the model and the responses to the remaining 6 stimuli as a test set. After training, the model fitted the responses to stimuli in the training sets very well and predicted the responses to stimuli in the test sets. Thus neuronal responses to colored patterns contain separate temporal codes representing color and pattern. 3. After establishing the model parameters, we obtained the waveforms that represented each neuron's temporal codes for the six colors and six patterns of our stimulus set. We then proceeded with a series of analyses to determine whether these waveforms were viable candidates for neuronal codes. Cluster analysis revealed that there were only a few different classes of waveforms representing each color and pattern, and there were many neurons in each class. Further, neurons that used similar waveforms to represent one color or pattern also tended to use similar waveforms to represent other colors or patterns. The waveforms representing five of the six colors and three of the six patterns were similar in the two monkeys used in this study. 4. We compared the shapes of the code waveforms across cortical areas and found no differences among areas in the shapes of the waveforms representing four of the six colors. In contrast, we found that there were differences among areas in the shapes of the waveforms representing all six patterns. These results suggest that messages about color are encoded at an early level and are then propagated upward, but that messages about pattern are altered in each successive cortical area. 5. Our results offer a neurophysiological explanation for the psychophysical evidence that color and form are processed by different channels. We propose that the psychophysical channels for color and pattern arise from the separability of the temporal codes for color and pattern in the responses of single neurons. This hypothesis implies that psychophysical channels correspond to classes of temporal codes rather than to classes of neurons. RP McClurkin, JW (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 49,RM 2A50,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 14 Z9 14 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 1996 VL 75 IS 1 BP 496 EP 507 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA TT526 UT WOS:A1996TT52600037 PM 8822573 ER PT J AU Fukuyama, R Brady, DR Rapoport, SI AF Fukuyama, R Brady, DR Rapoport, SI TI Development and application of a modified monoclonal hybridoma technique for isolating monoclonal antibodies to human brain regions (vol 59, pg 199, 1995) SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Correction DE hybridoma; antibody; entorhinal cortex; Western blot; regional vulnerability RP NIA, NIH, NEUROSCI LAB, BLDG 10, BETHESDA, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN PY 1996 VL 64 IS 1 BP 135 EP 135 DI 10.1016/0165-0270(94)00183-9 PG 1 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TZ412 UT WOS:A1996TZ41200016 PM 8869493 ER PT J AU Thompson, BG Pluta, RM Girton, ME Oldfield, EH AF Thompson, BG Pluta, RM Girton, ME Oldfield, EH TI Nitric oxide mediation of chemoregulation but not autoregulation of cerebral blood flow in primates SO JOURNAL OF NEUROSURGERY LA English DT Article DE nitric oxide; endothelial-derived relaxing factor; cerebral blood flow; cerebrovascular regulation; cynomolgus monkey ID PURIFIED GUANYLATE-CYCLASE; RELAXING FACTOR; L-ARGININE; SUBARACHNOID HEMORRHAGE; ENDOTHELIAL-CELLS; BASILAR ARTERY; INHIBITION; TONE; HYPERTENSION; RELAXATION AB The authors sought to develop a model for assessing in vivo regulation of cerebral vasoregulation by nitric oxide (NO), originally described as endothelial-derived relaxing factor, and to use this model to establish the role of NO in the regulation of cerebral blood flow (CBE) in primates. By using regional intraarterial perfusion, the function of NO in cerebral vasoregulation was examined without producing confounding systemic physiological effects. Issues examined were: whether resting vasomotor tone requires NO; whether NO mediates vasodilation during chemoregulation and autoregulation of CBF; and whether there is a relationship between the degree of hypercapnia and hypotension and NO production. Twelve anesthetized (0.5% isoflurane) cynomolgus monkeys were monitored continuously for cortical CBF, PaCO2, and mean arterial pressure (MAP), which were systematically altered to provide control and experi mental curves of chemoregulation (CBF vs. PaCO2) and autoregulation (CBF vs. MAP) during continuous intracarotid infusion of 1) saline and 2) an NO synthase inhibitor (NOSI), either L-n-monomethyl arginine or nitro L-arginine. During basal conditions (PaCO2 of 38-42 mm Hg) NOSI infusion of internal carotid artery (ICA) reduced cortical CBF from 62 (saline) to 53 ml/100 g/per minute (p < 0.01), although there was no effect on MAP. Increased CBF in response to hypercapnia was completely blocked by ICA NOSI. The difference in regional (r)CBF between TCA saline and NOSI infusion increased linearly with PaCO2 when PaCO2 was greater than 40 mm Hg, indicating a graded relationship of NO production, increasing PaCO2, and increasing CBF. Diminution of CBF with NOSI infusion was reversed by simultaneous ICA infusion of L-arginine, indicating a direct role of NO synthesis in the chemoregulation of CBF. Hypotension and hypertension were induced with trimethaphan camsylate (Arfonad) and phenylephrine at constant PaCO2 (40 +/- 1 mm Hg). Autoregulation in response to changes in MAP from 50 to 140 mm Hg was unaffected by ICA infusion of NOSI. In primates, cerebral vascular tone is modulated in vivo by NO; continuous release of NO is necessary to maintain homeostatic cerebral vasodilation; vasodilation during chemoregulation of CBF is mediated directly by NO production; autoregulatory vasodilation with hypotension is not mediated by NO; and increasing PaCO2 induces increased NO production. C1 NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NR 62 TC 83 Z9 84 U1 3 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 1996 VL 84 IS 1 BP 71 EP 78 DI 10.3171/jns.1996.84.1.0071 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA TL444 UT WOS:A1996TL44400011 PM 8613839 ER PT J AU Kalhan, SC Kim, SK AF Kalhan, SC Kim, SK TI Stable isotopic traces in nutrition and metabolism - Foreword SO JOURNAL OF NUTRITION LA English DT Editorial Material C1 NIH,DIV RES GRANTS,NUTR & METAB SCI INITIAL REVIEW GRP,NUTR STUDY SECT,BETHESDA,MD 20892. RP Kalhan, SC (reprint author), CASE WESTERN RESERVE UNIV,SCH MED,DEPT PEDIAT,CLEVELAND,OH 44106, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 1996 VL 126 IS 1 BP S347 EP S347 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TQ543 UT WOS:A1996TQ54300040 ER PT J AU Yergey, AL AF Yergey, AL TI Analytical instruments for stable isotopic tracers in mineral metabolism SO JOURNAL OF NUTRITION LA English DT Article DE trace minerals; mass spectrometry; calcium; magnesium; zinc; iron ID PLASMA MASS-SPECTROMETRY; FAST-ATOM-BOMBARDMENT; COUPLED ARGON PLASMA; BIOLOGICAL-MATERIALS; ZINC-ABSORPTION; ERYTHROCYTE INCORPORATION; COPPER ABSORPTION; IRON-ABSORPTION; ION-SOURCE; ICP-MS AB Thermal ionization mass spectrometry (TIMS) is the best of four currently used techniques for obtaining results of high accuracy and precision in studies of metal metabolism. TIMS is also the most general technique because it allows measurements of all the metallic elements of interest. The highest absolute sensitivity as well as the ability to determine multiple elements are simultaneously obtained with inductively coupled plasma mass spectrometry (ICP-MS). Current results with this technique show that, although element quantification may be done with acceptable accuracy and precision, use of ICP-MS in metabolic studies at low levels of isotopic labels may be limited. The most favorable elements for study using ICP-MS in metabolic studies appear to be Mg, Zn and possibly Fe. Use of this technique is limited further by isobaric interferences from plasma jet ion molecule reactions, and metabolic studies of Ca are particularly limited. Acceptable levels of accuracy and precision have been obtained from fast atom bombardment-secondary ion mass spectrometry (FAB-SIMS), which has allowed these approaches to be used in metabolic studies of ZN, Fe and Ca, but the approaches are ultimately limited by hydride isobaric interferences. Both FAB-SIMS and gas chromatography-mass spectrometry of metal chelates have the advantage of using widely available instrumentation. GC-MS of metal chelates has been shown to be useful in studies of Cr and Se metabolism and for the determination of a number of other metals. Values of accuracy and precision from use of this approach have been satisfactory. RP Yergey, AL (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 59 TC 17 Z9 17 U1 1 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 1996 VL 126 IS 1 BP S355 EP S361 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TQ543 UT WOS:A1996TQ54300042 PM 8558322 ER PT J AU Myers, AH Palmer, MH Engel, BT Warrenfeltz, DJ Parker, JA AF Myers, AH Palmer, MH Engel, BT Warrenfeltz, DJ Parker, JA TI Mobility in older patients with hip fractures: Examining prefracture status, complications, and outcomes at discharge from the acute-care hospital SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE hip fracture; hospitalization; elderly; mobility; outcomes; complications ID COGNITIVE IMPAIRMENT; URINARY-INCONTINENCE; PROSPECTIVE PAYMENT; ELDERLY PATIENTS; RISK-FACTORS; IMPACT; POPULATION; MANAGEMENT; MORTALITY; HEALTH AB The purpose of this study was to examine the relationships among prefracture status, development of complications, mobility outcomes at discharge, and disposition at discharge. We singled out a case series of consecutive noninstitutionalized elderly persons hospitalized for hip fracture (ICD 820.0-820.9) at two Baltimore hospitals during 1992-1993. Data were abstracted from the medical records for the following variables: sociodemographic information, prefracture status, selected medical conditions, injury and surgical treatment, complications, functional mobility and assistance needed at discharge, and disposition. Factors associated with four complications were identified from multiple logistic regression analyses. (a) Prefracture needs for assistance with activities of daily living (ADL), and age greater than or equal to 80, were associated with the development of pressure ulcers. (b) Male gender and prefracture urinary incontinence (UI) were associated with pneumonia. (c) Prefracture UI and weight-bearing status were associated with UI after removal of an indwelling catheter. (d) Age greater than or equal to 80 was associated with urinary retention. The amount of assistance needed for mobility tasks at discharge was associated with prefracture need for assistance with ADLs, gender, weight-bearing status, and hospitals with shorter lengths of stay and fewer physical therapy sessions. Patients who were older and had shorter lengths of stay and less physical therapy were more likely to go to another health facility than directly home. Prefracture status (ADL, prefracture UI) was significantly associated with the development of complications. Prefracture needs for assistance with ADL and complications were associated with mobility outcomes at discharge. These prefracture factors have an effect on outcomes and need to be addressed in the development of critical pathways for case treatment. Specific protocols for subgroups of patients may need to be designed and evaluated. C1 NINR,CLIN THERAPEUT LAB,BALTIMORE,MD. RP Myers, AH (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 44 TC 18 Z9 18 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PY 1996 VL 10 IS 2 BP 99 EP 107 DI 10.1097/00005131-199602000-00005 PG 9 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA TU448 UT WOS:A1996TU44800005 PM 8932668 ER PT J AU Magrath, IT AF Magrath, IT TI The molecular biology of Burkitt's lymphoma (BL) SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract C1 NCI,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0022-3417 J9 J PATHOL JI J. Pathol. PY 1996 VL 179 SU S BP A52 EP A52 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA VE907 UT WOS:A1996VE90700208 ER PT J AU Ruttimann, UE Pollack, MM AF Ruttimann, UE Pollack, MM TI Variability in duration of stay in pediatric intensive care units: A multiinstitutional study SO JOURNAL OF PEDIATRICS LA English DT Article ID MORTALITY; PATIENT AB Objective: Development of a statistical model to predict length of stay (LOS) in a pediatric intensive care unit (PICU) that adjusts for patient-related risk factors at admission. Design: Randomized selection of sites by cluster sampling from a 1989 national survey of all hospitals with PICUs, stratified for four quality-of-care factors into 16 clusters (size, presence of an intensive care specialist, medical school affiliation, coordination of care). The data collection was prospective in the selected units. Patients: 5415 consecutive medical, surgical, or emergency admissions to 16 PICUs. Measurements: Patients: Pediatric Risk of Mortality (PRISM) score for the initial 24 hours, admission diagnosis classified into system and cause of the primary dysfunction, operative status, preadmission care, critical care modalities required during the first 24 hours, age, sex, PICU length of stay, and outcome. PICU sites: admission volume, coordination of care, presence of an intensivist, presence of residents, and number of pediatric ICU and pediatric hospital beds. Methods: Log-logistic regression analysis of LOS on patient-related and institution-related factors. Results. Significant (p <0.05) patient-related predictors of LOS included PRISM, 10 diagnostic groups, 3 preadmission factors (operative status, inpatient/outpatient, previous PICU admission), and first-day use of mechanical ventilation. The ratio of observed to predicted LOS varied among PICUs from 0.83 to 1.25, with three PICUs displaying significantly (p <0.05) shorter and three PICUs longer LOS. The PICU factors associated (p <0.05) with shorter (5% to 11%) LOS were presence of an intensivist, presence of residents, and coordination of care, whereas an increased ratio of PICU to hospital beds was associated with longer (p <0.05) LOS. Medical school affiliation, admission volume, number of pediatric hospital beds, and PICU mortality rates did not have statistically significant effects on LOS when adjusted for patient conditions. Conclusions: The predictor can be used to adjust LOS in PICUs for patient-related risk factors, enabling the comparison of resource utilization among different institutions. Organizational factors known to foster team-oriented care are associated with shorter LOS, whereas increased relative PICU size may pose an incentive to keep PICU beds occupied longer. C1 CHILDRENS NATL MED CTR, CHILDRENS NATL MED CTR, CTR HLTH SERV & CLIN RES, WASHINGTON, DC 20010 USA. GEORGE WASHINGTON UNIV, SCH MED, DEPT PEDIAT, WASHINGTON, DC 20052 USA. GEORGE WASHINGTON UNIV, SCH MED, DEPT ANESTHESIOL, WASHINGTON, DC 20052 USA. NIAAA, ROCKVILLE, MD 20852 USA. FU PHS HHS [MCH-110584] NR 23 TC 60 Z9 60 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 1996 VL 128 IS 1 BP 35 EP 44 DI 10.1016/S0022-3476(96)70425-0 PG 10 WC Pediatrics SC Pediatrics GA TQ167 UT WOS:A1996TQ16700005 PM 8551419 ER PT J AU Moye, J Rich, KC Kalish, LA Sheon, AR Diaz, C Cooper, ER Pitt, J Handelsman, E AF Moye, J Rich, KC Kalish, LA Sheon, AR Diaz, C Cooper, ER Pitt, J Handelsman, E TI Natural history of somatic growth in infants born to women infected by human immunodeficiency virus SO JOURNAL OF PEDIATRICS LA English DT Article ID ANTHROPOMETRIC INDICATORS; BODY-COMPOSITION; CHILDREN; HORMONE; WEIGHT; INVITRO; BIRTH AB Objective. To evaluate the nature and magnitude of the effect of congenitally or perinatally acquired human immunodeficiency virus (HIV) infection on somatic growth from birth through 18 months of age. Study design: Anthropometry was performed serially in 282 term infants born to HIV-infected women in a multicenter prospective natural history cohort study. Repeated measures analysis was used to compare z-score anthropometric indexes of weight-for-age, length-for-age, weight-for-length, and head circumference-for-age between infected and uninfected infants, with adjustment for covariates including infant gender; maternal education; prenatal alcohol, tobacco, and/or illicit drug exposure; and mean prenatal CD4(+) T-lymphocyte count. A separate repeated measures model was used to assess the effect of infant zidovudine treatment on growth. Results: Infants infected with HIV were an estimated average 0.28 kg lighter and 1.64 cm shorter than uninfected infants at birth, were 0.71 kg lighter and 2.25 cm shorter by 18 months of age, and had a sustained estimated average decrement of 0.70 to 0.75 cm in head circumference. Patterns of growth were similar in male and female infants. Infected infants had a progressive decrement in body mass index from birth through 6 months of age. Infection with HIV was associated with significant decrements across all standardized growth outcome measures after adjustment for covariates. Mean z scores were lower for weight by 0.612 (p <0.001), for length by 0.735 (p <0.001), for weight-for-length by 0.255 (p = 0.02), and for head circumference by 0.563 (p <0.001) SD units compared with uninfected infants. Zidovudine treatment was not associated with improved growth. Conclusion: The effect of congenitally or perinatally acquired HIV infection on infant growth is one of early and progressive decrements in attained linear growth and growth in mass, early and sustained decrements in head growth, and marked early decrements in body mass index. C1 NIAID, DIV AIDS, VACCINE TRIALS & EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. UNIV ILLINOIS, DEPT PEDIAT, CHICAGO, IL USA. NEW ENGLAND RES INST, WATERTOWN, MA 02172 USA. UNIV PUERTO RICO, DEPT PEDIAT, SAN JUAN, PR 00936 USA. BOSTON UNIV, BOSTON CITY HOSP, SCH MED, DEPT PEDIAT, BOSTON, MA 02118 USA. COLUMBIA UNIV, COLL PHYS & SURG, DEPT PEDIAT, DIV INFECT DIS, NEW YORK, NY USA. SUNY HLTH SCI CTR, BROOKLYN, NY 11203 USA. RP Moye, J (reprint author), NICHHD, PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH, BETHESDA, MD 20892 USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [N01-AI-82505, N01-AI-85005]; NICHD NIH HHS [N01-HD-8-2913] NR 50 TC 93 Z9 97 U1 0 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 1996 VL 128 IS 1 BP 58 EP 69 DI 10.1016/S0022-3476(96)70428-6 PG 12 WC Pediatrics SC Pediatrics GA TQ167 UT WOS:A1996TQ16700008 PM 8551422 ER PT J AU Hirschfeld, S Laue, L Cutler, GB Pizzo, PA AF Hirschfeld, S Laue, L Cutler, GB Pizzo, PA TI Thyroid abnormalities in children infected with human immunodeficiency virus SO JOURNAL OF PEDIATRICS LA English DT Article ID THYROXINE-BINDING GLOBULIN; ENDOCRINE FUNCTION; HORMONE; PROGRESSION; CORTISOL; GROWTH; INJURY AB Objective: To study thyroid function in children infected with human immunodeficiency virus (HIV) and determine whether there are correlates of thyroid dysfunction with disease progression. Study design: Total and free thyroxine, triiodothyronine, reverse triiodothyronine, thyrotropin, and thyroxine binding globulin (TBG) were measured in 167 children with HIV infection (age, 1 to 19 years; mean, 9.15 years), Setting: Pediatric Blanch, National Cancer Institute. Results: Flee thyroxine was at or below the lower limit of normal (normal, 1.0 to 1.9 ng/dl) in 18% of the children; thyrotropin and TBG levels were above the normal range in 31% and 30%, respectively. There was an inverse correlation between CD4(+) cell count and thyrotropin, and between CD4(+) cell count and TBG, No correlation was found between thyroid function and other disease symptoms or medications. Conclusion: These findings indicate that thyroid abnormalities occur more frequently in children with HIV infection than was previously reported, have a different profile from the thyroid abnormalities associated with other chronic disease conditions, and correlate with disease progression. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP Hirschfeld, S (reprint author), NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 22 TC 21 Z9 22 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 1996 VL 128 IS 1 BP 70 EP 74 DI 10.1016/S0022-3476(96)70429-8 PG 5 WC Pediatrics SC Pediatrics GA TQ167 UT WOS:A1996TQ16700009 PM 8551423 ER PT J AU Vowells, SJ Fleisher, TA Sekhsaria, S Alling, DW Maguire, TE Malech, HL AF Vowells, SJ Fleisher, TA Sekhsaria, S Alling, DW Maguire, TE Malech, HL TI Genotype-dependent variability in flow cytometric evaluation of reduced nicotinamide adenine dinucleotide phosphate oxidase function in patients with chronic granulomatous disease SO JOURNAL OF PEDIATRICS LA English DT Article AB We studied phagocyte reduced nicotinamide adenine dinucleotide phosphate function to evaluate production of reactive oxygen species in both X-linked and autosomal forms of chronic granulomatous disease. We found a consistent and significant difference between the activated granulocyte response of the X-linked (gp91-phagocyte oxidase) form of chronic granulomatous disease (n = 18) and that of the most common autosomal recessive (p47-phagocyte oxidase) form of the disease (n = 17). The data indicate that mutations in the p47-phagocyte oxidase component of the reduced nicotinamide adenine dinucleotide phosphate oxidase component do not completely prevent oxidation despite severe defects in superoxide generation. C1 NIAID, HOST DEF LAB, BETHESDA, MD 20892 USA. NIH, CTR CLIN, SERV IMMUNOL, BETHESDA, MD 20892 USA. NR 9 TC 63 Z9 67 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 1996 VL 128 IS 1 BP 104 EP 107 DI 10.1016/S0022-3476(96)70437-7 PG 4 WC Pediatrics SC Pediatrics GA TQ167 UT WOS:A1996TQ16700016 PM 8551399 ER PT J AU Horsky, J Pitha, J AF Horsky, J Pitha, J TI Hydroxypropyl cyclodextrins: Potential synergism with carcinogens SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID BETA-CYCLODEXTRIN; AROMATIC-HYDROCARBONS; AQUEOUS-SOLUTIONS; BILE-SALTS; RATS AB The solubility of the lipophilic carcinogens benzo[a]pyrene and aflatoxin B-1 in water increases linearly and substantially with the concentration of hydroxypropyl beta-cyclodextrin present. Results of a kinetic study of naphthalene, a model for more potent carcinogens, indicate that the increase in the dissolution rate and in the transport through the aqueous phase into a nonpolar phase is on the same order of magnitude as the increase in solubility. Consequently, hydroxypropyl beta-cyclodextrin, when used in pharmaceutical formulations, has the potential to increase the absorption of carcinogens which enter the gastrointestinal tract either as food components or from air pollution through saliva. Only the above mechanism's simple proportionality needs be considered for estimating the increases in carcinogen absorption in the upper gastrointestinal tract and in the colon. In the presence of bile, however, additional factors are involved and the proportionality does not apply. Bile micelles, which themselves are effective solubilizers of lipophilic carcinogens, were disrupted by hydroxypropyl beta-cyclodextrin because of the formation of complexes with bile salts. Thus, in the presence of bile, two systems for delivery of carcinogens may coexist: that of cotransport with lipids and that of delivery through solubilization by hydroxypropyl beta-cyclodextrin. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RI Horsky, Jiri/G-3442-2014 NR 26 TC 14 Z9 14 U1 1 U2 4 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD JAN PY 1996 VL 85 IS 1 BP 96 EP 100 DI 10.1021/js9501324 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA TP970 UT WOS:A1996TP97000018 PM 8926593 ER PT J AU ThorntonManning, J Appleton, ML Gonzalez, FJ Yost, GS AF ThorntonManning, J Appleton, ML Gonzalez, FJ Yost, GS TI Metabolism of 3-methylindole by vaccinia-expressed P450 enzymes: Correlation of 3-methyleneindolenine formation and protein-binding SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CDNA-DIRECTED EXPRESSION; COVALENT BINDING; HUMAN-LIVER; RABBIT LUNG; IDENTIFICATION; INDOLE-3-CARBINOL; INHIBITION; SEQUENCE; ADDUCT; BIOACTIVATION AB The toxicity of 3-methylindole (3 MI), a selective pneumotoxin, is dependent upon cytochrome P450-mediated bioactivation(3). Using vaccinia-expressed P450 enzymes, the metabolites of radiolabeled 3 MI produced by 14 individual P450s were identified and quantified by high performance liquid chromatography. Indole-3-carbinol was produced from incubations of 3 MI with only four enzymes. Although 3-methyloxindole was a product of several P450s, human 1A2 was most efficient in producing this metabolite. The toxic intermediate of 3 MI is believed to be a reactive methylene imine, 3-methyleneindolenine. In this study, this intermediate was detected as its mercapturate adduct, when N-acetylcysteine was added to the incubations. 3-Methyleneindolenine was produced by CYP2A6 at a rate of 50.9 +/- 8.9 pmol/mg protein/hr and by CYP2F1 at a rate of 205.7 +/- 12.5 pmol/mg/hr. The mouse 1a-2 and rabbit 4B1 enzymes produced the reactive intermediate in amounts that exceeded that of the human 2F1 enzyme by 1.4-fold and 1.9-fold, respectively. The toxicity of 3 MI is believed to be due to covalent binding of a P450-generated intermediate to critical pulmonary proteins, Comparison of covalent binding studies to the formation of the metabolites revealed a strong correlation between the amount of the 3 MI adduct detected and covalent binding. This study showed that the methylene imine electrophile is produced by only a few P450 enzymes and is the metabolite responsible for the covalent binding and, presumably, the toxicity of 3 MI. Remarkable product preferences between the desaturation pathway to form the methyleneindolenine by CYP2F1 and the ring epoxidation pathway to form the oxindole by CYP1A2, were observed. C1 UNIV UTAH,DEPT PHARMACOL & TOXICOL,SALT LAKE CITY,UT 84112. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL13645, HL02119] NR 67 TC 68 Z9 74 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 1996 VL 276 IS 1 BP 21 EP 29 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TP439 UT WOS:A1996TP43900004 PM 8558432 ER PT J AU Hough, CJ Irwin, RP Gao, XM Rogawski, MA Chuang, DM AF Hough, CJ Irwin, RP Gao, XM Rogawski, MA Chuang, DM TI Carbamazepine inhibition of N-methyl-D-aspartate-evoked calcium influx in rat cerebellar granule cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RECEPTOR-MEDIATED INCREASES; NMDA RECEPTOR; (+/-)-5-AMINOCARBONYL-10,11-DIHYDRO-5H-DIBENZOCYCLOHEPTEN-5,10-IMIN E ADCI; TRICYCLIC ANTIDEPRESSANTS; HIPPOCAMPAL-NEURONS; AFFECTIVE-DISORDERS; CULTURE; DRUGS; DIZOCILPINE; MECHANISMS AB The effect of carbamazepine (CBZ) on N-methyl-D-aspartate (NMDA)-stimutated Ca++ influx in rat cerebellar granule cells was studied by use of fura-2 microfluorometry, CBZ inhibited the rise in intracellular free Ca++ concentration ([Ca++](i)) induced by NMDA and glycine in a rapid, reversible and concentration-dependent manner. CBZ's inhibition of the [Ca++](i) increase was noncompetitive with respect to NMDA, glycine and the facilitatory neurosteroid pregnenolone sulfate, The degree of inhibition of the NMDA response produced by CBZ increased with increasing concentrations of extracellular KCl. Excluding non-NMDA receptor-mediated contributions to Ca++ influx, depolarization by 50 mM KCl resulted in a 20-fold decrease (from 723 to 33 mu M) in the IC50 for CBZ blockade of the NMDA response. Thus, significant blockade of NMDA receptor responses in cerebellar granule cells can occur at concentrations of CBZ within the therapeutic range under conditions believed to accompany seizures. Moreover, the common toxic side effects of CBZ, which include signs of cerebellar dysfunction, may occur as a result of CBZ blockade of the NMDA receptors of cerebellar granule cells. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NINCDS,NEURONAL EXCITABIL SECT,BETHESDA,MD 20892. NINCDS,EPILEPSY RES BRANCH,BETHESDA,MD 20892. RP Hough, CJ (reprint author), NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BLDG 10,RM 3N-212,10 CTR DR,MSC 1272,BETHESDA,MD 20892, USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 37 TC 62 Z9 63 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 1996 VL 276 IS 1 BP 143 EP 149 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TP439 UT WOS:A1996TP43900020 PM 8558424 ER PT J AU McMahon, JB Buckheit, RW Gulakowski, RJ Currens, MJ Vistica, DT Shoemaker, RH Stinson, SF Russell, JD Bader, JP Narayanan, VL Schultz, RJ Brouwer, WG Felauer, EE Boyd, MR AF McMahon, JB Buckheit, RW Gulakowski, RJ Currens, MJ Vistica, DT Shoemaker, RH Stinson, SF Russell, JD Bader, JP Narayanan, VL Schultz, RJ Brouwer, WG Felauer, EE Boyd, MR TI Biological and biochemical anti-human immunodeficiency virus activity of UC 38, a new non-nucleoside reverse transcriptase inhibitor SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NONNUCLEOSIDE INHIBITORS; HIV-1 REPLICATION; VIRAL RESISTANCE; TYPE-1; DERIVATIVES; INVITRO; POTENT AB UC 38, a simple analog of oxathin carboxanilide, UG 84, lacking the oxathin ring, was found to be a potent inhibitor of human immunodeficiency virus (HIV)-1-induced cell killing and HIV replication in a variety of human cell fines, as well as in human peripheral blood lymphocytes and macrophages. UC 38 was active against a wide range of biologically diverse laboratory and clinical strains of HIV-1. However, UC 38 was inactive against HIV-2 and both nevirapine- and pyridinone-uesistant strains of HIV-1. UC 38 selectively inhibited HIV-1 reverse transcriptase (RT), but not HIV-2 RT. Combination of UC 38 with 3'-azido-3'-deoxythymidine synergistically, inhibited HIV-induced cell killing. An HIV-1 isolate resistant to UC 38 was selected in cell culture, and the mutations in the RT nucleotide sequences were determined. Comparison with the wild-type RT sequence revealed an amino acid change at position 181 (Tyr to Cys). The UC 38-resistant virus was found to be cross-resistant to a variety of structurally diverse non-nucleoside RT inhibitors. UC 38 was susceptible to rapid degradation in vitro and in vive; yet, nontoxic in vive concentrations of UC 38 many-fold in excess of the in vitro effective concentrations could be achieved and maintained after s.c. or p.o. administration in hamsters. These results establish UC 38 as a new chemotype within the general class of HIV-1-specific RT inhibitors. the favorable physical characteristics, lack of toxicity, potency and bioavailability of UC 38 may make it a candidate for combination chemotherapy of acquired immune deficiency syndrome. C1 NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,FREDERICK,MD 21702. NR 36 TC 6 Z9 6 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 1996 VL 276 IS 1 BP 298 EP 305 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TP439 UT WOS:A1996TP43900041 PM 8558446 ER PT J AU Dudek, SM AF Dudek, SM TI A discussion of activity-dependent forms of synaptic weakening and their possible role in ocular dominance plasticity SO JOURNAL OF PHYSIOLOGY-PARIS LA English DT Article DE long-term depression; homosynaptic plasticity; heterosynaptic plasticity; binocular competition; Hebbian synapse; BCM model ID LONG-TERM DEPRESSION; CAT VISUAL-CORTEX; PHOSPHOINOSITIDE TURNOVER; ANESTHETIZED RATS; CRITICAL PERIOD; DENTATE GYRUS; AREA CA1; HIPPOCAMPUS; POTENTIATION; INDUCTION AB Activity-dependent synaptic weakening is likely to be involved in numerous types of developmentally regulated cortical plasticity. The possible roles of two models of synaptic weakening, homosynaptic- and heterosynaptic-long-term-depression (LTD), are discussed. Metabotropic glutamate receptors (mGluRs) as they relate to LTD and ocular dominance plasticity will also be considered. RP NICHHD, NATL INST HLTH, BLDG 49, ROOM 5A38, 49 CONVERT DR, BETHESDA, MD 20892 USA. OI Dudek, Serena M./0000-0003-4094-8368 NR 36 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0928-4257 EI 1769-7115 J9 J PHYSIOL-PARIS JI J. Physiol.-Paris PY 1996 VL 90 IS 3-4 BP 167 EP 170 DI 10.1016/S0928-4257(97)81417-9 PG 4 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WN395 UT WOS:A1996WN39500006 PM 9116661 ER PT J AU Wiener, L Riekert, K Pizzo, PA Siegel, K Battles, H AF Wiener, L Riekert, K Pizzo, PA Siegel, K Battles, H TI Exploratory study of residents' perceptions of a housing facility for pediatric patients and family members SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article AB The National Association of Children's Hospitals and Related Institutions (NACHRI) estimates that between 3 million and 4 million children are hospitalized in the United States each year (NACHRI, personal communication, August 13, 1996). As hospital care has become more regionalized and specialized, families have had to travel greater distances to receive health care (Home Away Front Home, 1989). These treatments can be prolonged, and housing costs associated with this temporary relocation can be substantial. The existing literature documents a tremendous need for low-cost housing near medical centers to minimize lodging costs and to reduce the time and expense related to traveling to and from the hospital as well as the emotional stress experienced by patients and families (Home Away Front Home, 1989). When residential services are available, parents do not have the additional burden of finding temporary and affordable housing near the treatment facility. Despite these facts, little research has been conducted on residential services for pediatric patients and their families. Ronald McDonald Houses are residential facilities provided for pediatric patients and their families while the child is receiving care at a medical center away from home. Two articles have recently been published about these Ronald McDonald Houses (Hamilton, 1991; Sanford, 1993). These descriptive articles tend to focus mainly on the history of Ronald McDonald Houses, available facilities and services, financial information, patient demographics, and administrative facts such as occupancy rates. although these facilities appear to reduce the financial and psychological strain on families, empirical data to support this assertion are lacking. C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. HARVARD UNIV,SCH MED,CHAIR PEDIAT,BOSTON,MA. CHILDRENS HOSP,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,DEPT SOCIAL WORK,NEW YORK,NY 10021. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP Wiener, L (reprint author), NCI,PEDIAT BRANCH,PEDIAT HIV PSYCHOSOCIAL SUPPORT PROGRAM,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 1996 VL 14 IS 3 BP 69 EP 80 DI 10.1300/J077V14N03_05 PG 12 WC Psychology, Social SC Psychology GA VZ978 UT WOS:A1996VZ97800005 ER PT J AU Horowitz, AM AF Horowitz, AM TI Introduction to the symposium on minimal intervention techniques for caries SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT IADR Symposium on Minimal Intervention Techniques for Dental Caries, as part of the 73rd General Session of the International-Association-for-Dental-Research CY JUN 28-JUL 01, 1995 CL SINGAPORE, SINGAPORE SP Int Assoc Dent Res DE dental caries management; ART; tooth conservation AB Although dental caries has declined precipitously in many industrialized countries, this disease has escalated in less developed countries. Moreover, dental caries remains a public health problem even in most industrialized countries because the disease frequently is more prevalent among subpopulations without access to preventive regimens and treatment In some developing countries where dental facilities and providers are rare, alternative measures for managing frank lesions are being used. One example of these minimal intervention techniques is ''Atraumatic Restorative Treatment'' (ART). This procedure, endorsed and actively promoted by the World Health Organization, requires no anesthetic and its costs are minimal. This symposium addresses several aspects and issues of minimal intervention techniques for caries management. RP Horowitz, AM (reprint author), NIDR,NIH,BLDG 45,ROOM 3AN-44B,BETHESDA,MD 20892, USA. NR 11 TC 11 Z9 12 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PY 1996 VL 56 IS 3 SI SI BP 133 EP 134 DI 10.1111/j.1752-7325.1996.tb02422.x PG 2 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA VN838 UT WOS:A1996VN83800003 PM 8915957 ER PT J AU Scott, DB AF Scott, DB TI The dawn of a new era SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT Proceedings of the International Symposium Celebrating the 50th Anniversary of Water Fluoridation CY SEP, 1995 CL GRAND RAPIDS, MI DE wafer fluoridation; dental caries; Grand Rapids fluoridation study; age of prevention; age of caries control; history of water fluoridation AB This paper reviews the scientific events culminating in the fluoridation of communal water supplies. Dental and medical studies completed by 1942 had established the safety and benefits of exposure to drinking water naturally containing fluoride. Researchers and public health workers concluded that it was possible to test the hypothesis that the dental benefits attained where fluoride levels around I ppm occurred naturally in drinking water could be safely replicated in low-fluoride areas by raising the level to this optimal concentration. Grand Rapids became the first test site and by the time the demonstration ended in 1959, around 40 million people in about 2,000 communities already were drinking water with fluoride levels that had been adjusted to optimal. The success of fluoridation brought the dawn of the era of caries control and created great opportunities for research and public health. C1 NIDR,NIH,BETHESDA,MD 20892. NR 7 TC 2 Z9 3 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PY 1996 VL 56 IS 5 SI SI BP 235 EP 238 DI 10.1111/j.1752-7325.1996.tb02444.x PG 4 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA WG338 UT WOS:A1996WG33800002 PM 9034966 ER PT J AU Slavkin, HC AF Slavkin, HC TI And the next 50 years? The future of recombinant DNA technology in oral medicine SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT Proceedings of the International Symposium Celebrating the 50th Anniversary of Water Fluoridation CY SEP, 1995 CL GRAND RAPIDS, MI DE craniofacial, oral, and dental diseases; transcription factors, growth factors, and cognate receptors; recombinant DNA technology; animal models; human disease genes; genetically engineered vaccines; viral and bacterial diseases ID COLLINS SYNDROME LOCUS; HOMEOBOX GENES; DISTAL-LESS; DEVELOPING FOREBRAIN; EXPRESSION PATTERNS; TRANSGENIC MICE; RIEGER SYNDROME; GROWTH-FACTORS; IN-VITRO; MOUSE AB As we celebrate this spectacular 50th anniversary, fluoridation continues to be the most effective public health strategy to reduce the disease burden of dental caries. Curiously, while N. Trendley Dean and his colleagues at the National Institutes of Health were investigating the effects of fluoride on tooth enamel in the mid-1930s, two young boys, one in London and the other in Chicago, were growing up to become the catalysts for another ''biological revolution. '' These two very talented individuals, James Watson and Francis Crick, would later meet by accident at Cambridge and produce their seminal discovery published in April 1953 as a letter in Nature, a one-page article provoking an international scientific adventure to understand living organisms in terms of the structure and function of deoxyribonucleic acid (DNA), a universal genetic code and a rationale for the applications of recombinant DNA Technology (rDNA) in fields as diverse as agriculture, energy, industry and health. As we now reflect upon the triumphs from fluoridation and ponder the next 50 years and the complexities of craniofacial, oral, and dental diseases, it becomes increasingly evident that recombinant DNA technology coupled with health promotion, disease prevention, and public education offers the promise for remarkable advances in prevention, diagnosis, and therapeutics in oral medicine. RP Slavkin, HC (reprint author), NIDR, NIH, 31 CTR DR, BLDG 31C, ROOM 2C39, BETHESDA, MD 20892 USA. NR 68 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PY 1996 VL 56 IS 5 SI SI BP 278 EP 285 DI 10.1111/j.1752-7325.1996.tb02452.x PG 8 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA WG338 UT WOS:A1996WG33800010 PM 9034974 ER PT J AU Baum, BJ AF Baum, BJ TI The dental curriculum: What should be new in the 21st century? SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT Proceedings of the International Symposium Celebrating the 50th Anniversary of Water Fluoridation CY SEP, 1995 CL GRAND RAPIDS, MI DE dental education; biology; health care delivery system; economic factors; 21st century ID HEALTH-CARE; MEDICINE; REFORM AB Dental education is at a critical juncture. The success of water fluoridation has reduced the caries burden of Americans and, consequently, has raised questions about the disproportionate technical emphasis on treating the sequelae of caries in US dental schools. Additionally, several powerful external factors-such as changing demographics, advances in biological science, fundamental changes in our health care delivery system, and a modest US economy-are forcing dental educators to question the appropriateness of retaining the current dental curriculum into the 21st century. The author considers These factors, suggests what type of dentist will be needed by society in approximately 20 years, and concludes that today's dental educational system is inadequate to produce such a dentist Several elements, in addition to technical excellence, are required for the dental curriculum, including major changes in pedagogy, relevant science training, practical fluency in medicine, an increased mix of stomatologic skills, and broader contact with other health care providers. RP Baum, BJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BLDG 10,ROOM 1N113,10 CTR DR,MSC 1190,BETHESDA,MD 20892, USA. NR 23 TC 8 Z9 8 U1 0 U2 1 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PY 1996 VL 56 IS 5 SI SI BP 286 EP 290 DI 10.1111/j.1752-7325.1996.tb02453.x PG 5 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA WG338 UT WOS:A1996WG33800011 PM 9034975 ER PT J AU Pak, MD Fishman, PH AF Pak, MD Fishman, PH TI Anomalous behavior of CGP 12177A on beta(1)-adrenergic receptors SO JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; HUMAN BETA-2-ADRENERGIC RECEPTOR; HUMAN BETA-3-ADRENERGIC RECEPTOR; HUMAN BETA-1-ADRENERGIC RECEPTOR; TERNARY COMPLEX MODEL; BROWN ADIPOSE-TISSUE; ADENYLATE-CYCLASE; CYCLIC-AMP; MOLECULAR-CLONING; DOWN-REGULATION AB CGP 12177A originally was developed as a hydrophilic antagonist to detect cell surface beta(1)- and beta(2)-adrenergic receptors, and subsequently was found to be a partial agonist for the atypical or beta(3)-adrenergic receptor. Using hamster cells stably expressing either the human beta(1)-, human beta(2)- or rat beta(1)-adrenergic receptor, we found that CGP 12177A behaved as an agonist for beta(1)-adrenergic receptors. Whereas at low concentrations, CGP 12177A behaved as an antagonist and inhibited isoproterenol stimulation of adenylyl cyclase activity, at higher concentrations, it stimulated a response even in the absence of isoproterenol. The agonistic properties of CGP 12177A were positively correlated with the level of beta(1)-adrenergic receptor expression. Thus, at low receptor densities, CGP 12177A behaved as a weak, partial agonist whereas as high receptor densities, the drug was a full agonist. At similar high densities of the beta(2)-adrenergic receptor, CGP 12177A acted only as a partial agonist. Competition binding studies to membranes from cells expressing beta(1)-adrenergic receptors indicated that similar to 90% of the receptors were in a high affinity, guanine nucleotide-insensitive state for CGP 12177A whereas similar to 10% of the receptors were in a lower affinity, guanine nucleotide-sensitive state for CGP 12177A. We propose that the latter receptors are precoupled to stimulatory G proteins and recognize CGP 12177A as an agonist whereas the high affinity, uncoupled receptors recognize CGP 12177A as an antagonist. C1 NINCDS,MEMBRANE BIOCHEM SECT,CELLULAR & MOLEC NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 44 TC 69 Z9 70 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1079-9893 J9 J RECEPT SIGNAL TR R JI J. Recept. Signal Transduct. Res. PY 1996 VL 16 IS 1-2 BP 1 EP 23 DI 10.3109/10799899609039938 PG 23 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UP020 UT WOS:A1996UP02000001 PM 8771528 ER PT J AU Castle, PE Dean, J AF Castle, PE Dean, J TI Molecular genetics of the zona pellucida: Implications for immunocontraceptive strategies SO JOURNAL OF REPRODUCTION AND FERTILITY LA English DT Article; Proceedings Paper CT International Symp on Prospects of Zona Pellucida Glycoproteins for Immunocontraception, at 7th Annual Conf of Indian-Society-for-the-Study-of-Reproduction-and-Fertility CY DEC 02-05, 1995 CL NEW DELHI, INDIA SP Indian Soc Study Reprod & Fertil, Natl Inst Immunol, New Delhi ID SPERM RECEPTOR ACTIVITY; OOCYTE-SPECIFIC EXPRESSION; O-LINKED OLIGOSACCHARIDES; MOUSE OOCYTES; MONOCLONAL-ANTIBODIES; DEVELOPMENTAL REGULATION; GLYCOPROTEIN ZP3; PROTEIN; GENES; FERTILIZATION AB Successful immunocontraceptive agents must prevent fertilization without compromising the health of the individual exposed to immunization. The zona pellucida, which surrounds all mammalian eggs and is unique to the female gamete, represents a potential target for immunocontraception. Mouse and human zonae pellucidae are composed of three glycoproteins, designated ZP1, ZP2 and ZP3. The genes are conserved and the transcripts that encode the zona proteins have been characterized in both species. In mice, the expression of the zona genes is oocyte specific. The recent elucidation of the primary structure of the zona proteins in a number of species has provided critical information for the rational design of a contraceptive vaccine. We and others have demonstrated that both passive and active immunization strategies that target individual zona proteins can prevent fertilization. Although various contraceptive strategies have been tested in a laboratory setting, the applicability of these protocols to humans remains to be determined. The recent revolution in transgenesis coupled with the cloning of the human zona pellucida genes provide the means to produce animal models for testing immunocontraceptive strategies that target human zona proteins. These models could provide a system for the initial evaluation of vaccine candidates prior to trials in primates. RP Castle, PE (reprint author), NIDDK, CELLULAR & DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 39 TC 0 Z9 0 U1 0 U2 1 PU SOC REPRODUCTION FERTILITY PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE CB5 8DT, ENGLAND SN 0022-4251 J9 J REPROD FERTIL JI J. Reprod. Fertil. PY 1996 SU 50 BP 1 EP 8 PG 8 WC Reproductive Biology SC Reproductive Biology GA VL292 UT WOS:A1996VL29200002 ER PT J AU Alexander, NJ Schlaff, WD AF Alexander, NJ Schlaff, WD TI Highlights of the symposium SO JOURNAL OF REPRODUCTION AND FERTILITY LA English DT Editorial Material C1 UNIV COLORADO, HLTH SCI CTR, DEPT OBSTET & GYNECOL, DENVER, CO 80262 USA. RP Alexander, NJ (reprint author), NIH, CONTRACEPT DEV BRANCH, POPULAT RES CTR, 6100 EXECUT BLVD, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC REPRODUCTION FERTILITY PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE CB5 8DT, ENGLAND SN 0022-4251 J9 J REPROD FERTIL JI J. Reprod. Fertil. PY 1996 SU 50 BP 191 EP 194 PG 4 WC Reproductive Biology SC Reproductive Biology GA VL292 UT WOS:A1996VL29200024 ER PT J AU Svikis, DS Brooner, RK Rutigliano, P Gazaway, P Fagan, P Gupman, A AF Svikis, DS Brooner, RK Rutigliano, P Gazaway, P Fagan, P Gupman, A TI Psychosexual functioning in opioid-dependent women SO JOURNAL OF SEX RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 13, 1993 CL TORONTO, CANADA SP Coll Problems Drug Dependence ID INTRAVENOUS-DRUG-USERS; SEXUAL BEHAVIORS; AFRICAN-AMERICAN; SUBSTANCE-ABUSE; OPIATE ADDICTS; INFECTION; DSFI AB Psychosexual functioning of opioid-dependent women (N = 63) was compared to a socioeconomically similar group of non-drug-abusing women (N = 53) using the Derogatis Sexual Functioning Inventory (DSFI). Initial analyses revealed differences in sexual drive, liberal attitude, and both masculine and feminine gender-role affiliation. When demographic differences between the two groups were statistically controlled however, only liberal attitude and femininity subscale differences remained significant. Although both opioid-dependent and comparison group women reported similar types of sexual experiences (lifetime), opioid-dependent women reported greater recent reduction in sexual behaviors related to anal intercourse and anal stimulation. Both opioid-dependent and clinic women differed significantly from the DSFI normative sample, highlighting the importance of controlling for demographic differences when using standardized psychological assessment tools. Implications of study findings for AIDS prevention and intervention with drug-dependent women are discussed. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 31 TC 0 Z9 0 U1 0 U2 0 PU SOC SCIENTIFIC STUDY SEX INC PI MT VERNON PA PO BOX 208, MT VERNON, IA 52314 SN 0022-4499 J9 J SEX RES JI J. Sex Res. PY 1996 VL 33 IS 2 BP 103 EP 111 PG 9 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA UV436 UT WOS:A1996UV43600003 ER PT J AU Trus, BL Kocsis, E Conway, JF Steven, AC AF Trus, BL Kocsis, E Conway, JF Steven, AC TI Digital image processing of electron micrographs: The PIC system-III SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; ESCHERICHIA-COLI; SIMIAN VIRUS-40; RECONSTRUCTION; MICROSCOPY; CRYSTALLINE; SUBUNIT; MASS; SPECIMENS; SYMMETRY AB The PIC system is an integrated package of image processing software written in Fortran and G. Throughout its 16 years of continuous development, PIG has been designed for the processing of electron micrographs with emphasis on the particular requirements for structural analysis of biological macromolecules. PIG has been implemented on successive generations of Digital Equipment Corporation dedicated minicomputers and workstations, The latest version, PIG-III, runs on Alpha workstations and represents a substantial upgrading in functionality compared with PIG-II, the VAX version previously described (B. L. Trus et al. (1992), Scanning Microsc. Suppl. 6, 441-451), PIG now possesses an X-windows menu-driven graphical user interface that many be utilized from both local or remote X-window terminals or workstations. Other new features include dynamic memory allocation; an open systems approach to interfacing with other image processing software packages; interface options with visualization software; and programs to reconstruct three-dimensional density maps of both helical filaments and free-standing particles with and without symmetry. (C) 1996 Academic Press, Inc. C1 NIAMSD,NIH,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RP Trus, BL (reprint author), NIAMSD,NIH,COMPUTAT BIOSCI & ENGN LAB,DIV COMP RES & TECHNOL,BLDG 12A,ROOM 2033,BETHESDA,MD 20892, USA. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 40 TC 42 Z9 42 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN-FEB PY 1996 VL 116 IS 1 BP 61 EP 67 DI 10.1006/jsbi.1996.0011 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TX606 UT WOS:A1996TX60600011 PM 8742724 ER PT J AU Conway, JF Trus, BL Booy, FP Newcomb, WW Brown, JC Steven, AC AF Conway, JF Trus, BL Booy, FP Newcomb, WW Brown, JC Steven, AC TI Visualization of three-dimensional density maps reconstructed from cryoelectron micrographs of viral capsids SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; FROZEN-HYDRATED SPECIMENS; 3-DIMENSIONAL RECONSTRUCTION; EQUINE HERPESVIRUS-1; ELECTRON-MICROGRAPHS; MICROSCOPY; IMAGES; NEUTRALIZATION; REPRESENTATION; RESOLUTION AB Full evaluation of three-dimensional density maps calculated from cryoelectron micrographs of complex supramolecular structures requires that the maps be sifted by a variety of complementary visualization techniques. We present here a primer for a number of such techniques in current widespread use, including surface rendering; serial sections; simulated motion; and real-time manipulation of tiled surfaces displayed on an advanced workstation, The principles on which these techniques operate are briefly reviewed, as are their advantages and limitations, with emphasis on the requirements for visual representation of viral capsid structures. These methods are illustrated in application to a density map of herpes simplex virus type 1 (HSV-1) capsid at 24 Angstrom resolution, which reveals more detailed information than heretofore concerning the inner surface of the icosahedral capsid shell and the 150-Angstrom-long channels that pass through each of the 162 capsomers. (C) 1996 Academic Press, Inc. C1 NIAMSD,NIH,STRUCT BIOL LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMPUTAT BIOSCI & ENGN LAB,BETHESDA,MD 20892. UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,CTR CANC,CHARLOTTESVILLE,VA 22908. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 FU NIAID NIH HHS [AI-1375549] NR 44 TC 29 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN-FEB PY 1996 VL 116 IS 1 BP 200 EP 208 DI 10.1006/jsbi.1996.0031 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TX606 UT WOS:A1996TX60600031 PM 8742744 ER PT J AU Steven, AC Baumeister, W AF Steven, AC Baumeister, W TI Special issue: Advances in computational image processing for microscopy SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Editorial Material C1 MAX PLANCK INST BIOCHEM,D-82152 MARTINSRIED,GERMANY. RP Steven, AC (reprint author), NIAMS,STRUCT BIOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN-FEB PY 1996 VL 116 IS 1 BP 248 EP 249 DI 10.1006/jsbi.1996.0038 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TX606 UT WOS:A1996TX60600038 ER PT J AU Grant, BF AF Grant, BF TI Prevalence and correlates of drug use and DSM-IV drug dependence in the United States: Results of the National Longitudinal Alcohol Epidemiologic Survey SO JOURNAL OF SUBSTANCE ABUSE LA English DT Article ID PSYCHIATRIC-DISORDERS; INTERVIEW SCHEDULE; COMORBIDITY-SURVEY AB This study presents updated estimates of the prevalence and examines the correlates of drug use and dependence in a representative sample of the U.S. population. The prevalence of lifetime drug use was 15.6%, with 4.9% of the respondents reporting drug use during the past 12 months. Lifetime and 12-month prevalence of drug dependence were estimated at 2.9% and 0.8%, respectively. Men were significantly more likely to use drugs than women, and drug use and dependence were much more common among cohorts born after World War II. The data indicated that rates of dependence among women were quickly approaching the rates among men in the younger cohorts. Members of the youngest cohort, between the ages of 18 and 24 years at the time of the interview, were more likely to use drugs, to become dependent, and to persist in dependence compared to the older cohorts, including Cohort 2 who experienced adolescence at the height of widespread introduction of illicit drugs among youth in the mid-1960s. The demographic correlates of first use, onset of dependence, and persistence of dependence varied as a function of the stage of progression. Implications of these findings are discussed in terms of changes over time in drugs of choice and dependence liability and vulnerability among recent drug users. RP Grant, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 22 TC 90 Z9 91 U1 7 U2 12 PU ABLEX PUBL CORP PI NORWOOD PA 355 CHESTNUT ST, NORWOOD, NJ 07648 SN 0899-3289 J9 J SUBST ABUSE JI J. SUBST. ABUSE PY 1996 VL 8 IS 2 BP 195 EP 210 DI 10.1016/S0899-3289(96)90249-7 PG 16 WC Substance Abuse SC Substance Abuse GA VG726 UT WOS:A1996VG72600004 PM 8880660 ER PT J AU Dawson, DA AF Dawson, DA TI Gender differences in the probability of alcohol treatment SO JOURNAL OF SUBSTANCE ABUSE LA English DT Article ID GENERAL-POPULATION; WOMEN ALCOHOLICS; MEN; SEEKING; ABUSE; ENTRY AB Interview data from 7,359 adults 18 years of age and over who met the DSM-IV criteria for alcohol abuse or dependence at some point during their lives revealed that 23.0% of the men and 15.1% of the women ever received treatment for alcohol problems. The median interval from onset of disorder to first treatment was between 2 and 3 years longer for men than women. This difference did not result from women being more likely than men to initiate treatment shortly after onset of an alcohol use disorder, but rather from men being more likely than women to initiate treatment in the period well after onset. Excluding treatment initiated prior to the clinical onset of the disorders or after cessation of drinking, men's and women's cumulative conditional probabilities of having initiated treatment by 30 years after onset of alcohol abuse or dependence were .424 and .356, respectively. Within the first 8 years after onset of abuse or dependence, men's and women's probabilities of initiating treatment were about the same, but men were 13% to 20% more likely to initiate treatment in the period from 8 to 25 years after onset Use of proportional hazards models to adjust for factors including sociodemographic characteristics, prior consumption, severity of disorder, and comorbid drug use and depression revealed that men's and women's likelihoods of ever having received treatment did not differ for the most severely affected, those with 20 or more symptoms of abuse or dependence. Among those less severely affected, the male-re-female ratio in the likelihood of treatment declined with severity from 1.75 (1 symptom) to 1.24 (15 symptoms). RP Dawson, DA (reprint author), NIAAA,DBE,WILLCO BLDG,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 44 TC 40 Z9 41 U1 2 U2 4 PU ABLEX PUBL CORP PI NORWOOD PA 355 CHESTNUT ST, NORWOOD, NJ 07648 SN 0899-3289 J9 J SUBST ABUSE JI J. SUBST. ABUSE PY 1996 VL 8 IS 2 BP 211 EP 225 DI 10.1016/S0899-3289(96)90260-6 PG 15 WC Substance Abuse SC Substance Abuse GA VG726 UT WOS:A1996VG72600005 PM 8880661 ER PT J AU Johnstone, PAS Sindelar, WF AF Johnstone, PAS Sindelar, WF TI Radical reoperation for advanced pancreatic carcinoma SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE adjuvant therapy; pancreatic cancer; resection ID ADENOCARCINOMA; SURGERY; CANCER AB The indications and outcomes of aggressive reoperation in patients referred to the National Cancer Institute (NCI) for protocol therapy of locally advanced pancreatic carcinoma were investigated. Twenty-nine patients referred to the NCI after exploration and determination of unresectability elsewhere were considered to have localized disease after a metastatic work-up. These patients were then entered onto NCI adjuvant therapy protocols and taken to exploratory laparotomy. Intraoperatively, patients underwent complete resection if possible; otherwise varying palliative surgical procedures were performed. Of the 29 patients, 16 underwent complete resection of their disease, and 13 were unresectable. Two patients suffered postoperative mortality. Disease-specific survival of the resected patients was significantly better than that of the unresectable patients (P < 0.01). The two long-term survivors (53 and >109 months) underwent definitive surgery after a palliative procedure elsewhere. Complete resection of pancreatic carcinoma contributes to increased survival. The intraoperative definition of unresectability in pancreatic cancer varies with the degree of pancreatitis present, the surgical expertise of the surgeon, and the available ancillary services. Given the extremely grave prognosis of patients with unresectable pancreatic carcinoma, locally unresectable patients without peritoneal seeding or distant metastases at exploration should be considered for referral for protocol therapy to centers where expertise in radical surgery for pancreatic cancer exists. (C) 1996 Wiley-Liss, Inc.* C1 USN,MED CTR,DEPT RADIOL,DIV RADIAT ONCOL,SAN DIEGO,CA 92134. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NATL CANC INST,SURG BRANCH,BETHESDA,MD. RP Johnstone, PAS (reprint author), USN,MED CTR,DEPT CLIN INVEST,SAN DIEGO,CA 92134, USA. NR 10 TC 10 Z9 10 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JAN PY 1996 VL 61 IS 1 BP 7 EP 11 DI 10.1002/(SICI)1096-9098(199601)61:1<7::AID-JSO2>3.0.CO;2-H PG 5 WC Oncology; Surgery SC Oncology; Surgery GA TQ289 UT WOS:A1996TQ28900002 PM 8544466 ER PT J AU Jensen, PS Irwin, RAC Josephson, AM Davis, H Xenakis, SN Bloedau, L Ness, R Mabe, A Lee, B Traylor, J Clawson, L AF Jensen, PS Irwin, RAC Josephson, AM Davis, H Xenakis, SN Bloedau, L Ness, R Mabe, A Lee, B Traylor, J Clawson, L TI Data-gathering tools for ''real world'' clinical settings: A multisite feasibility study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE research methods; clinical database; knowledge transfer; services research; patient registry; assessment ID ATTENTION DEFICIT DISORDER; PSYCHOTHERAPY-RESEARCH; PSYCHIATRY; CHILD AB Objective: To determine the mental health needs and optimal treatments for children and families in ''real world'' settings, data-gathering strategies are needed that can be easily implemented across a variety of clinical settings. To address this need, the authors developed and piloted a ''clinician-friendly'' questionnaire that includes demographic, psychosocial, medical, and family history variables, such as those routinely gathered in standard clinical evaluations. Method: Optical scanning technology was used to encode data from more than 1,900 children, including 1,458 consecutive referrals in four military child psychiatry clinics, 285 consecutive admissions to a civilian psychiatric state hospital, 71 pediatric patients, and a community sample of 113 children. Results: Despite geographic and logistic obstacles, clinical data were reliably obtained across multiple settings. Data analyses revealed meaningful differences across samples in subjects' presenting complaints, and a range of psychosocial, demographic, and background variables. Data were characterized by an apparently high degree of accuracy and completeness. Conclusions: Findings illustrate the importance and feasibility of standardized data-gathering approaches in routine clinical settings and clarify the hazards as well as the opportunities afforded by these research approaches. Such data-gathering tools appear to have significant merit and deserve further implementation and testing across a range of clinical and research settings. C1 MED COLL GEORGIA,AUGUSTA,GA 30912. EISENHOWER ARMY MED CTR,FT GORDON,GA. AUGUSTA COLL,AUGUSTA,GA 30904. TRIPLER ARMY MED CTR,HONOLULU,HI 96859. RP Jensen, PS (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROOM 18C-17,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 22 TC 15 Z9 15 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 1996 VL 35 IS 1 BP 55 EP 66 DI 10.1097/00004583-199601000-00013 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA TL432 UT WOS:A1996TL43200013 PM 8567613 ER PT J AU Chilcoat, HD Anthony, JC AF Chilcoat, HD Anthony, JC TI Impact of parent monitoring on initiation of drug use through late childhood SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE child; parenting; substance abuse ID SUBSTANCE USE; RISK-FACTORS; SCHOOL; ADOLESCENCE; PREDICTORS; BEHAVIORS; STUDENTS; CARE AB Objective: To examine whether parental supervision and monitoring in middle childhood might have a sustained impact on risk of drug use later in childhood and adolescence. Method: An epidemiological sample of 926 urban-dwelling youths were individually interviewed annually, beginning in 1989 when the children were 8 to 10 years old, continuing through 1992. Standardized questions measured drug use, parenting behaviors, and other suspected determinants of drug use. Results: Survival analysis estimates indicated that children in the lowest quartile of parent monitoring initiated drug use at earlier ages. The contrast in risk of initiating alcohol, tobacco, or other drug use across levels of parent monitoring was greatest when children were under 11 years old; at older ages there was no difference in risk. However, in analyses focused specifically on marijuana, cocaine, and inhalant drugs, we observed a sustained higher risk of starling to use these drugs among youths who had been monitored at the lowest levels in middle childhood. Conclusion: These results add to the chain of inference that effective supervision and monitoring in middle childhood by parents or guardians might induce a delay or prevent onset of drug use among youths living in urban areas, a hypothesis that now ought to be tested in rigorous field experiments. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. NIDA,DIV INTRAMURAL RES,ETIOL BRANCH,BALTIMORE,MD. RP Chilcoat, HD (reprint author), HENRY FORD HLTH SCI CTR,DEPT PSYCHIAT,1 FORD PL,3A,DETROIT,MI 48202, USA. FU NIDA NIH HHS [DA04392]; NIMH NIH HHS [MH42968] NR 24 TC 157 Z9 159 U1 3 U2 20 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 1996 VL 35 IS 1 BP 91 EP 100 DI 10.1097/00004583-199601000-00017 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA TL432 UT WOS:A1996TL43200018 PM 8567618 ER PT J AU Shiota, T Jones, M Yamada, I Heinrich, RS Ishii, M Sinclair, B Yoganathan, AP Sahn, DJ AF Shiota, T Jones, M Yamada, I Heinrich, RS Ishii, M Sinclair, B Yoganathan, AP Sahn, DJ TI Evaluation of aortic regurgitation with digitally determined color Doppler-imaged flow convergence acceleration: A quantitative study in sheep SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MITRAL REGURGITATION; VALVULAR REGURGITATION; CONTINUOUS-WAVE; ORIFICE; QUANTIFICATION; INVITRO; VOLUME; REGION; INSUFFICIENCY; IMPACT AB Objectires. The aim of the present study was to validate a digital color Doppler-based centerline velocity/distance acceleration profile method for evaluating the severity of aortic regurgitation. Background. Clinical and in vivo experimental applications of the Bow convergence axial centerline velocity/distance profile method have recently been used to estimate regurgitant Bow rates and regurgitant volumes in the presence of mitral regurgitation. Methods. In six sheep, a total of 19 hemodynamic states were obtained pharmacologically 14 weeks after the original operation in which a portion of the aortic noncoronary (n = 3) or right coronary (n = 3) leaflet was excised to produce aortic regurgitation. Echocardiographic studies were performed to obtain complete proximal axial flow acceleration velocity/distance profiles during the time of peak regurgitant flow (usually early in diastole) for each hemodynamic state. For each steady state, the severity of aortic regurgitation was assessed by measurement of the magni tude of the regurgitant flow volume/beat, regurgitant fraction and instantaneous regurgitant Bow rates determined by using both aortic and pulmonary artery electromagnetic flow probes. Results. Grade I regurgitation (regurgitant volume/beat <15 ml, six conditions), grade II regurgitation (regurgitant volume/ beat between 16 ml and 30 ml, five conditions) and grade III-IV regurgitation (regurgitant volume/beat >30 ml, eight conditions) were clearly separated by using the color Doppler centerline velicity/distance profile domain technique. Additionally, an equation for correlating ''a'' (the coefficient from the multiplicative curve fit for the velocity/distance relation) with the peak regurgitant flow rates (Q [liters/min]) was derived showing a high correlation between calculated peak flow rates by the color Doppler method and the actual peak how rates (Q = 13a + 1.0, r = 0.95, p < 0.0001, SEE = 0.76 liters/min). Conclusions. This study, using quantified aortic regurgitation, demonstrates that the flow convergence axial centerline velocity/ distance acceleration profile method can be used to evaluate the severity of aortic regurgitation. C1 NHLBI,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. GEORGIA INST TECHNOL,ATLANTA,GA 30332. FU NHLBI NIH HHS [HL43287] NR 35 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN PY 1996 VL 27 IS 1 BP 203 EP 210 DI 10.1016/0735-1097(95)00392-4 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TN261 UT WOS:A1996TN26100028 PM 8522696 ER PT J AU Slavkin, HC AF Slavkin, HC TI 'The flu zone' SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JAN PY 1996 VL 127 IS 1 BP 127 EP 129 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TP748 UT WOS:A1996TP74800019 PM 8568090 ER PT J AU Handa, VL Landerman, R Hanlon, JT Harris, T Cohen, HJ AF Handa, VL Landerman, R Hanlon, JT Harris, T Cohen, HJ TI Do older women use estrogen replacement? Data from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE) SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID POSTMENOPAUSAL WOMEN; HORMONE-THERAPY; RISK-FACTORS; DISEASE; OSTEOPOROSIS; FRACTURES; BLACK; HIP AB OBJECTIVES: The primary purpose of this study was to determine the prevalence of current and past estrogen use among older, community-dwelling, postmenopausal women. The secondary purpose was to describe factors associated with estrogen use in this population. DESIGN: A survey. SETTING: The Piedmont region of North Carolina. PARTICIPANTS: The sample included 2602 community-dwelling women over the age of 65 who were interviewed for the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). MEASUREMENTS: Current and past use of estrogen. RESULTS: Of the women surveyed, 6.1% reported current estrogen use, and 18.5% reported past use. Approximately half of the participants reported using estrogen for more than 2 years. Multivariate analysis demonstrated that current estrogen users were younger, more affluent, had smaller families, and were more likely to be white and to live in an urban area than were never users. Current users were also more likely to drink alcohol and to take calcium supplements; and compared with past estrogen users, they were more likely to be white, have smaller families, and to drink alcohol. CONCLUSION: Estrogen replacement therapy is used by a small minority of older women, especially blacks. Moreover, although women with some risk factors for osteoporosis are more likely to use estrogen, the chief determinants of estrogen utilization are socioeconomic. C1 DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DIV GERIATR,DURHAM,NC 27710. UNIV N CAROLINA,SCH PHARM,DURHAM,NC. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,DURHAM,NC. FU NIA NIH HHS [N01-AG-1-2102, K07 AG033174] NR 35 TC 76 Z9 76 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 1996 VL 44 IS 1 BP 1 EP 6 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TP328 UT WOS:A1996TP32800001 PM 8537578 ER PT J AU Vaitkevicius, PV Fleg, JL AF Vaitkevicius, PV Fleg, JL TI An abnormal exercise treadmill test in an asymptomatic older patient SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID CORONARY-ARTERY DISEASE; ELDERLY PATIENTS; MYOCARDIAL-ISCHEMIA; ELECTROCARDIOGRAPHY; SCINTIGRAPHY C1 NIA,JOHNS HOPKINS BAYVIEW MED CTR,CTR GERONTOL RES,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS SCH MED,DIV GERIATR MED,BALTIMORE,MD. NR 25 TC 5 Z9 5 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 1996 VL 44 IS 1 BP 83 EP 88 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TP328 UT WOS:A1996TP32800014 PM 8537597 ER PT J AU Lancaster, FW Ulvila, JW Humphrey, SM Smith, LC Allen, B Herner, S AF Lancaster, FW Ulvila, JW Humphrey, SM Smith, LC Allen, B Herner, S TI Evaluation of interactive knowledge-based systems: Overview and design for empirical testing SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Article ID EXPERT SYSTEMS; COLLECTION DEVELOPMENT; SELECTION AB An overview of levels and approaches in the evaluation of knowledge-based systems is presented. There is a need for empirical studies using objective criteria in advance of completing the technical evaluation of such systems. A methodology for this type of evaluation developed for a particular knowledge-based indexing system is presented. It is suggested that the proposed study may serve as a model for the design of any evaluation in which the results of existing intellectual procedures are compared with results achieved when these procedures are aided by use of an appropriate expert system. C1 DECIS SCI ASSOCIATES, MANASSAS, VA 22110 USA. NATL LIB MED, LISTER HILL NATL CTR BIOMED COMMUN, BETHESDA, MD 20894 USA. HERNER & CO, ARLINGTON, VA 22201 USA. RP Lancaster, FW (reprint author), UNIV ILLINOIS, GRAD SCH LIB & INFORMAT SCI, CHAMPAIGN, IL 61820 USA. NR 52 TC 7 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD JAN PY 1996 VL 47 IS 1 BP 57 EP 69 DI 10.1002/(SICI)1097-4571(199601)47:1<57::AID-ASI6>3.0.CO;2-1 PG 13 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA TK884 UT WOS:A1996TK88400006 ER PT J AU Xu, YD Zhang, X Yergey, AL AF Xu, YD Zhang, X Yergey, AL TI Electrospray ionization of copper-glycine solutions SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID MASS-SPECTROMETRY; METAL-IONS; GAS-PHASE; ALKALINE-EARTH; LARGE BIOMOLECULES; AQUEOUS-SOLUTION; AMINO-ACIDS; COMPLEXES; EVAPORATION; EQUILIBRIA AB We have characterized the electrospray ionization (ESI) spectra of mixtures of the 3d transition metal ion CU2+ with both a model amino acid (glycine) and a simple peptide system (glycylglycine). We found what appear to be two major classes of ions. We suggest that these apparent classes may offer some further insight into the nature of the ion formation process in ESI. Specifically, we argue that one group of ions is a consequence of gas-phase reactions of the intramolecular charge transfer type. We also argue that the second group of ions has a close association with species that have been identified in the bulk phase, and which therefore may arise in ESI by a direct desorption process. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NR 38 TC 27 Z9 27 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JAN PY 1996 VL 7 IS 1 BP 25 EP 29 DI 10.1016/1044-0305(95)00625-7 PG 5 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA TT648 UT WOS:A1996TT64800003 PM 24202791 ER PT J AU Wu, GH Zhang, FT Salley, RK Diana, JN Su, TP Chien, SF AF Wu, GH Zhang, FT Salley, RK Diana, JN Su, TP Chien, SF TI Delta opioid extends hypothermic preservation time of the lung SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID EURO-COLLINS SOLUTION; FLUSH PERFUSION; TRANSPLANTATION; HIBERNATION; ISCHEMIA; NALOXONE; MODEL; RAT; INDUCTION; TRIGGER AB To test the hypothesis that a delta opioid, DADLE ([D-Ala(2), D-Leu(5)]-enkephalin), could protect tissue from ischemic damage during hypothermic lung preservation, we studied three groups of rats, In group 1 (n = 8), lung function was studied immediately after harvesting, In group 2 (n = 8), the lung was flushed with 4 degrees C Euro-Collins solution and preserved for 24 hours. In group 3 (n = 8), the lung was hushed with 4 degrees C Euro-Collins solution plus DADLE (1 mg/kg) and preserved for 23 hours, Lung function was studied by using a living rat perfusion model, Venous blood from the host rat perfused the pulmonary artery of the isolated lung, Blood from the isolated lung was returned to the carotid artery of the host rat with a roller pump, Severe pulmonary edema, hemorrhage, and occlusive pulmonary artery resistance occurred in group 2 within 30 minutes of perfusion, Perfusion studies were carried out for more than 60 minutes in groups 1 and 3, Pulmonary blood flow was lower in group 2 than in either group 1 or group 3, Pulmonary vascular resistance was much higher in group 2 than in groups 1 and 3 (p < 0.05). Airway pressure and airway resistance were much higher in group 2 than in groups 1 and 3 (p < 0.05), Airway resistance was also higher in group 3 than in group 1 after 20 minutes of perfusion (p < 0.05). Oxygen tensions from the pulmonary vein of the isolated lung in group 2 were lower than those in groups 1 and 3 (p < 0.05). Alveolar-arterial oxygen difference was much higher in group 2 than in groups 1 and 3 (p < 0.05). Lung tissue wet/dry weight ratio after perfusion was much higher in group 2 than in groups 1 and 3. The results clearly show, for the first time, that DADLE can effectively enhance hypothermic lung preservation in rats. C1 UNIV KENTUCKY,MED CTR,DEPT SURG,LEXINGTON,KY 40536. UNIV KENTUCKY,MED CTR,DEPT PHYSIOL & BIOPHYS,LEXINGTON,KY 40536. NIDR,IRP,BALTIMORE,MD. FU NHLBI NIH HHS [HL-36552]; NIGMS NIH HHS [GM-43890] NR 35 TC 18 Z9 20 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 1996 VL 111 IS 1 BP 259 EP 267 DI 10.1016/S0022-5223(96)70424-5 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA TQ336 UT WOS:A1996TQ33600040 PM 8551774 ER PT J AU Mao, Y Liu, KJ Jiang, JJ Shi, XL AF Mao, Y Liu, KJ Jiang, JJ Shi, XL TI Generation of reactive oxygen species by Co(II) from H2O2 in the presence of chelators in relation to DNA damage and 2'-deoxyguanosine hydroxylation SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID HYDROGEN-PEROXIDE; SINGLET OXYGEN; FREE-RADICALS; SODIUM CHROMATE(VI); SUPEROXIDE; COBALT(II); CARCINOGENESIS; MECHANISM; ESR; PHENANTHROLINE AB The generation of reactive oxygen species by Co(II) from H2O2 in the presence of chelators and related DNA damage was investigated by electron spin resonance (ESR), electrophoretic assays, and high-performance liquid chromatography (HPLC). Incubation of Co(II) with beta-alanyl-3-methyl-L-histidine (anserine) and H2O2 generated (OH)-O-. radicals. Omission of any one component sharply reduced the amount of (OH)-O-. radicals generated, indicating that anserine modulated the oxidation potential of Co(II) to enhance its capability to generate (OH)-O-. radicals from H2O2. Formate only moderately decreased the (OH)-O-. radical generation, while ethanol had no observable effect, indicating that the generation of (OH)-O-. radical is site specific. The metal ion chelator I, 10-phenanthroline reduced the (OH)-O-. radical generation, and deferoxamine suppressed it with the formation of deferoxamine nitroxide radical. Electrophoretic assays using both lambda Hind III linear DNA and PM2 supercoiled DNA showed that (OH)-O-. radicals generated from a mixture of Co(II), H2O2, and anserine caused DNA strand breaks. A mixture of Co(II), H2O2, and I,10-phenanthroline also caused DNA strand breaks, which were inhibited by sodium azide, indicating that O-1(2) was involved in DNA damage. HPLC measurements showed that (OH)-O-. radicals and O-1(2) generated by Co(II) reactions caused 2'-deoxyguanosine hydroxylation to form 8-hydroxy-2'-deoxyguanosine. ESR spin trapping measurements provided evidence for O-1(2), generation by Co(II) from H2O2 in the presence of I, 10-phenanthroline. The results indicate that the oxidation potential of Co(II) can be modulated by chelators to facilitate its generation of reactive oxygen species from H2O2. These species may be involved in Co(II)-induced cellular damage. C1 NCI,LAB EXPTL PATHOL,BETHESDA,MD 20892. DARTMOUTH COLL SCH MED,DEPT RADIOL,HANOVER,NH. RI Shi, Xianglin/B-8588-2012 NR 36 TC 31 Z9 32 U1 1 U2 4 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD JAN PY 1996 VL 47 IS 1 BP 61 EP 75 DI 10.1080/009841096161933 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TR340 UT WOS:A1996TR34000005 PM 8568912 ER PT J AU Aus, G Hugosson, J Norlen, L Abrahamsson, PA Adami, HO Taube, A Kim, KM Zelen, M Kulldorff, M AF Aus, G Hugosson, J Norlen, L Abrahamsson, PA Adami, HO Taube, A Kim, KM Zelen, M Kulldorff, M TI Long-term survival and mortality in prostate cancer treated with noncurative intent SO JOURNAL OF UROLOGY LA English DT Letter C1 UPPSALA UNIV,DEPT CANC EPIDEMIOL,S-75120 UPPSALA,SWEDEN. UPPSALA UNIV,DEPT STAT,S-75120 UPPSALA,SWEDEN. HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. NCI,DCPC,BIOMETRY BRANCH,BETHESDA,MD 20892. RP Aus, G (reprint author), LUND UNIV,DEPT UROL,LUND,SWEDEN. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 1996 VL 155 IS 1 BP 296 EP 297 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA TJ434 UT WOS:A1996TJ43400122 ER PT J AU Brokaw, JL Blanco, M McBride, AA AF Brokaw, JL Blanco, M McBride, AA TI Amino acids critical for the functions of the bovine papillomavirus type 1 E2 transactivator SO JOURNAL OF VIROLOGY LA English DT Article ID CARBOXY-TERMINAL DOMAIN; E1 REPLICATION PROTEIN; OPEN READING FRAMES; TRANSCRIPTIONAL ACTIVATION; MUTATIONAL ANALYSIS; TRANSFORMED CELLS; TRANS-ACTIVATOR; DNA-REPLICATION; MOUSE CELLS; ORIGIN AB The N-terminal domain of the bovine papillomavirus type 1 E2 protein is important for viral DNA replication, for transcriptional transactivation, and for interaction with the El protein. To determine which residues of this 200-amino-acid domain are important for these activities, single conservative amino acid substitutions have been generated in 17 residues that are invariant among all papillomavirus E2 proteins. The resulting mutated E2 proteins were tested for the ability to support viral DNA replication, activate transcription, and cooperatively bind to the origin of replication with the El protein, We identified five mutated proteins that were completely defective for transcriptional activation and either were defective or could support viral DNA replication at only low levels. However, several of these proteins could still interact efficiently with the El protein, In addition, we identified several mutated proteins that were unable to efficiently cooperatively bind to the origin with the El protein, Although a number of the mutated proteins demonstrated wild-type activity in all of the functions tested, only 3 out of 17 mutated viral genomes were able to induce foci in a C127 focus formation assay when the mutations were generated in the background of the entire bovine papillomavirus type 1 genome, This finding suggests that the E2 protein may have additional activities that are important for the viral life cycle. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. OI McBride, Alison/0000-0001-5607-5157 NR 42 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1996 VL 70 IS 1 BP 23 EP 29 PG 7 WC Virology SC Virology GA TJ650 UT WOS:A1996TJ65000004 PM 8523530 ER PT J AU Kurokohchi, K Akatsuka, T Pendleton, CD Takamizawa, A Nishioka, M Battegay, M Feinstone, SM Berzofsky, JA AF Kurokohchi, K Akatsuka, T Pendleton, CD Takamizawa, A Nishioka, M Battegay, M Feinstone, SM Berzofsky, JA TI Use of recombinant protein to identify a motif-negative human cytotoxic T-cell epitope presented by HLA-A2 in the hepatitis C virus NS3 region SO JOURNAL OF VIROLOGY LA English DT Article ID NON-B-HEPATITIS; TOXIC LYMPHOCYTES-T; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; CHRONIC NON-A; HEPATOCELLULAR-CARCINOMA; CYTO-TOXICITY; INFECTION; PEPTIDES; ANTIGEN AB To define cytotoxic T-cell (CTL) epitopes, the common approach involving the use of a series of overlapping synthetic peptides covering the whole protein sequence is impractical for large proteins. Motifs identify only a fraction of epitopes. To identify human CTL epitopes in the NS3 region of hepatitis C virus (HCV), we modified an approach using recombinant protein and the ability of short peptides to bind to class I major histocompatibility complex (MHC) molecules. Peripheral blood mononuclear cells from an HCV-infected patient were stimulated dth a proteolytic digest of the recombinant NS3 protein to expand CTL to any active peptides in the digest. The digest was fractionated by reverse-phase high-performance liquid chromatography, and fractions were assessed for the ability to sensitize targets for lysis by CTL. The most active fraction was sequenced, identifying a 15-residue peptide (NS3-1J; TITTGAPVTYSTYGK). This sequence was confirmed to be the source of the activity by synthesis of the corresponding peptide. CTL lines specific for NS3-1J were established from two HCV-infected patients (both HLA-A2 and -B7 positive) by stimulation with the synthetic peptide in vitro. The CTL were HLA-A2 restricted, and the minimal epitope was mapped to a decapeptide NS3-1J (10.4). As this minimal epitope lacks the common HLA-A2-binding motif, this technique is useful for mapping CTL epitopes independent of known motifs and without the requirement for enormous numbers of overlapping peptides. Because this peptide is presented by the most common HLA class I molecule, present in almost half the population, it might be a useful component of a vaccine against HCV. C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,HEPATITIS RES LAB,BETHESDA,MD 20892. KAGAWA MED SCH,DIV INTERNAL MED 3,MIKI,KAGAWA 76107,JAPAN. OSAKA UNIV,RES FDN MICROBIAL DIS,KANONJI,KAGAWA 768,JAPAN. NR 78 TC 44 Z9 44 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1996 VL 70 IS 1 BP 232 EP 240 PG 9 WC Virology SC Virology GA TJ650 UT WOS:A1996TJ65000030 PM 8523531 ER PT J AU Ribas, JC Wickner, RB AF Ribas, JC Wickner, RB TI Saccharomyces cerevisiae L-BC double-stranded RNA virus replicase recognizes the L-A positive-strand RNA 3' end SO JOURNAL OF VIROLOGY LA English DT Article ID POL FUSION PROTEIN; Q-BETA REPLICASE; GAG-POL; MESSENGER-RNA; COAT PROTEIN; YEAST; INVITRO; EXPRESSION; ENCAPSIDATION; PARTICLES AB L-A and L-BC are two double-stranded RNA viruses present in almost all strains of Saccharomyces cervisiae. L-A, the major species, has been extensively characterized with in vitro systems established, but little is known about L-BC, Here we report in vitro template-dependent transcription, replication, and RNA recognition activities of L-BC. The L-BC replicase activity converts positive, single stranded RNA to double-stranded RNA by synthesis of the complementary RNA strand, Although L-A and L-BC do not interact in vivo, in vitro L-BC virions can replicate the positive, single-stranded RNA of L-A and its satellite, M(1), with the same 3' end sequence and stem-loop requirements shown by L-A virions for its own template, However, the L-BC virions do not recognize the internal replication enhancer of the L-A positive strand. In a direct comparison of L-A and L-BC virions, each preferentially recognizes its own RNA for binding, replication, and transcription, These results suggest a close evolutionary relation of these two viruses, consistent with their RNA-dependent RNA polymerase sequence similarities. C1 NIDDKD,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892. RI Ribas, Juan/C-9864-2015 OI Ribas, Juan/0000-0001-6430-0895 NR 52 TC 6 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1996 VL 70 IS 1 BP 292 EP 297 PG 6 WC Virology SC Virology GA TJ650 UT WOS:A1996TJ65000037 PM 8523538 ER PT J AU Freed, EO Martin, MA AF Freed, EO Martin, MA TI Domains of the human immunodeficiency virus type 1 matrix and gp41 cytoplasmic tail required for envelope incorporation into virions SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; TRANSMEMBRANE PROTEIN; INTRACELLULAR-TRANSPORT; MUTATIONAL ANALYSIS; FUSION ACTIVITY; MATURE VIRIONS; GAG-PROTEINS; HOST-RANGE; CELL-TYPES; GLYCOPROTEIN AB We recently demonstrated that a single amino acid substitution in matrix residue 12 (12LE) or 30 (30LE blocks the incorporation of human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins into virions and that this block can be reversed by pseudotyping,vith heterologous retroviral envelope glycoproteins with short cytoplasmic tails or by truncating the cytoplasmic tail of HIV-1 transmembrane glycoprotein gp41 by 104 or 144 amino acids, In this study, we mapped the domain of the gp41 cytoplasmic tail responsible for the block to incorporation into virions by introducing a series of eight truncation mutations that eliminated 23 to 93 amino acids from the C terminus of gp41. We found that incorporation into virions of a HIV-1 envelope glycoprotein with a deletion of 23, 30, 51, or 56 residues from the C terminus of gp41 is specifically blocked by the 12LE matrix mutation, whereas truncations of greater than 93 amino acids reverse this defect. To elucidate the role of matrix residue 12 in this process, we introduced a number of additional single amino acid substitutions at matrix positions 12 and 13. Charged substitutions at residue 12 blocked envelope incorporation and virus infectivity, whereas more subtle amino acid substitutions resulted in a spectrum of envelope incorporation defects, To characterize further the role of matrix in envelope incorporation into virions, we obtained and analyzed second-site revertants to two different matrix residue 12 mutations. A Val-->Ile substitution at matrix amino acid 34 compensated for the effects of both amino acid 12 mutations, suggesting that matrix residues 12 and 33 interact during the incorporation of HIV-1 envelope glycoproteins into nascent virions. RP Freed, EO (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,RM 307,BETHESDA,MD 20892, USA. NR 70 TC 266 Z9 266 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1996 VL 70 IS 1 BP 341 EP 351 PG 11 WC Virology SC Virology GA TJ650 UT WOS:A1996TJ65000044 PM 8523546 ER PT J AU Hasenkrug, KJ Brooks, DM Nishio, J Chesebro, B AF Hasenkrug, KJ Brooks, DM Nishio, J Chesebro, B TI Differing T-cell requirements for recombinant retrovirus vaccines SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; HOST IMMUNE-RESPONSE; FRIEND-VIRUS; GENETIC-CONTROL; LYMPHOCYTES-T; MOLECULAR-BIOLOGY; ENV GENE; RECOVERY; IDENTIFICATION; ANTIBODIES AB Friend murine leukemia virus is a retrovirus complex that induces rapid erythroleukemia and immunosuppression in susceptible strains of adult mice. Using this model, we directly examined the T-cell subsets required for a protective retrovirus vaccine. Paradoxically, recovery in mice immunized with a chimeric envelope containing only T-helper (T-H) and B-cell epitopes was dependent on CD8(+) T cells as well as CD4(+) T cells despite the fact that the vaccine contained no CD8(+) cytolytic T-Lymphocyte (CTL) epitopes, However, the requirement for CD8(+) T cells was overcome by inclusion of additional T-H and B-cell epitopes in the immunizing protein. These additional epitopes primed for more rapid production of virus-neutralizing antibody which appeared to limit virus spread sufficiently to protect even in the absence of CD8(+) T cells. Inclusion of an immunodominant CTL epitope in the vaccine was not sufficient to overcome dependence on CD4(+) T cells, These data suggest that T-H priming is more critical for retrovirus immunity than CTL priming. RP Hasenkrug, KJ (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 35 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1996 VL 70 IS 1 BP 368 EP 372 PG 5 WC Virology SC Virology GA TJ650 UT WOS:A1996TJ65000047 PM 8523549 ER PT J AU Ludert, JE Feng, NG Yu, JH Broome, RL Hoshino, Y Greenberg, HB AF Ludert, JE Feng, NG Yu, JH Broome, RL Hoshino, Y Greenberg, HB TI Genetic mapping indicates that VP4 is the rotavirus cell attachment protein in vitro and in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID SA-11 ROTAVIRUS; BINDING; NEUTRALIZATION; GLYCOPROTEIN; INFECTION; CULTURE; IDENTIFICATION; HEMAGGLUTININ; DETERMINANTS; PURIFICATION AB To identify the rotavirus protein which mediates attachment to cells in culture, viral reassortants between the simian rotavirus strain RRV and the murine strains EHP and EW or between the simian strain SA-11 and the human strain DS-1 were isolated. These parental strains differ in the requirement for sialic acid to bind and infect cells in culture. Infectivity and binding assays with the parental and reassortant rotaviruses indicate that gene 4 encodes the rotaviros protein which mediates attachment to cells in culture for both sialic acid-dependent and -independent strains, Using ligated intestinal segments of newborn mice and reassortants obtained between the murine strain EW and RRV, we developed an in vivo infectivity assay, In this system, the infectivity of EW was not affected by prior treatment of the enterocytes with neuraminidase, while neuraminidase treatment reduced the infectivity of a reassortant carrying gene 4 from RRV on an EW background more than 80% relative to the controls, Thus, VP4 appears to function as the cell attachment protein in vivo as well as in vitro. C1 STANFORD UNIV,SCH MED,DIV GASTROENTEROL,DEPT MED MICROBIOL & IMMUNOL,STANFORD,CA 94305. NIAID,BETHESDA,MD 20892. RP Ludert, JE (reprint author), VET ADM MED CTR,DIV GASTROENTEROL 154C,3801 MIRANDA AVE,PALO ALTO,CA 94304, USA. FU NIAID NIH HHS [R01AI21632]; NIDDK NIH HHS [DK38707] NR 41 TC 88 Z9 89 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1996 VL 70 IS 1 BP 487 EP 493 PG 7 WC Virology SC Virology GA TJ650 UT WOS:A1996TJ65000058 PM 8523562 ER PT J AU Karczewski, MK Strebel, K AF Karczewski, MK Strebel, K TI Cytoskeleton association and virion incorporation of the human immunodeficiency virus type 1 Vif protein SO JOURNAL OF VIROLOGY LA English DT Article ID INTERMEDIATE FILAMENTS; INFECTED-CELLS; DNA-SYNTHESIS; SOR GENE; HIV-1; EXPRESSION; VIMENTIN; MUTANTS; TRANSMISSION; REPLICATION AB The human immunodeficiency virus type 1 (HIV-1) Vif protein has an important role in the regulation of virus infectivity. This function of Vif is cell type specific, and virions produced in the absence of Vif in restrictive cells have greatly reduced infectivity. We show here that the intracellular localization of Vif is dependent on the presence of the intermediate filament vimentin. Fractionation of acutely infected T cells or transiently transfected HeLa cells demonstrates the existence of a soluble and a cytoskeletal form and to a lesser extent the presence of a detergent-extractable form of Vif. Confocal microscopy suggests that in HeLa cells, Vif is predominantly present in the cytoplasm and closely colocalizes with the intermediate filament vimentin. Treatment of cells with drugs affecting the structure of vimentin filaments affect the localization of Vif accordingly, indicating a close association of Vif with this cytoskeletal component. The association of Vif with vimentin can cause the collapse of the intermediate filament network into a perinuclear aggregate. In contrast, analysis of Vif in vimentin-negative cells reveals significant staining of the nucleus and the nuclear membrane in addition to diffuse cytoplasmic staining. In addition to the association of Vif with intermediate filaments, analyses of virion preparations demonstrate that Vif is incorporated into virus particles. In sucrose density gradients, Vif cosediments with capsid proteins even after detergent treatment of virus preparations, suggesting that Vif is associated with the inner core of HIV particles. We propose a model in which Vif has a crucial function as a virion component either by regulating virus maturation or following virus entry into a host cell possibly involving an interaction with the cellular cytoskeletal network. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 50 TC 131 Z9 135 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1996 VL 70 IS 1 BP 494 EP 507 PG 14 WC Virology SC Virology GA TJ650 UT WOS:A1996TJ65000059 PM 8523563 ER PT J AU Yasutomi, Y Robinson, HL Lu, S Mustafa, F Lekutis, C Arthos, J Mullins, JI Voss, G Manson, K Wyand, M Letvin, NL AF Yasutomi, Y Robinson, HL Lu, S Mustafa, F Lekutis, C Arthos, J Mullins, JI Voss, G Manson, K Wyand, M Letvin, NL TI Simian immunodeficiency virus-specific cytotoxic T-lymphocyte induction through DNA vaccination of rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Note ID MACAQUES; PROTECTION; INFECTION; INJECTION; VACCINES; GENE AB In view of the growing evidence that virus-specific cytotoxic T lymphocytes (CTL) play an important role in containing the early spread of human immunodeficiency virus type 1 (HIV-1) in infected individuals, novel vaccine strategies capable of eliciting HIV-1-specific CTL are being pursued in attempts to create an effective AIDS vaccine. We have used the simian immunodeficiency virus of macaques (SIVmac)/rhesus monkey model to explore the induction of AIDS virus-specific CTL responses by DNA vaccination. We found that the inoculation of rhesus monkeys with plasmid DNA encoding SIVmac Env and Gag elicited a persisting SiVmac-specific memory CTL response. These CTL were CD8(+) and major histocompatibility complex class I restricted. These studies provide evidence for the potential utility of DNA inoculation as an approach to an HIV-1 vaccine. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV VIRAL PATHOGENESIS,BOSTON,MA 02215. UNIV MASSACHUSETTS,MED CTR,DEPT PATHOL,WORCESTER,MA 01655. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195. TSI MASON LABS INC,WORCESTER,MA 01608. FU NCI NIH HHS [CA-50139]; NIAID NIH HHS [AI-15114, AI-35166] NR 30 TC 127 Z9 132 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1996 VL 70 IS 1 BP 678 EP 681 PG 4 WC Virology SC Virology GA TJ650 UT WOS:A1996TJ65000087 PM 8523593 ER PT J AU Lipman, RD Chrisp, CE Hazzard, DWG Bronson, RT AF Lipman, RD Chrisp, CE Hazzard, DWG Bronson, RT TI Pathologic characterization of Brown Norway, Brown Norway x Fischer 344, and Fischer 344 x Brown Norway rats with relation to age SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID BODY-WEIGHT; NUTRITIONAL INFLUENCES; DIETARY RESTRICTION; AGING RESEARCH; SURVIVAL; GROWTH; MODEL; MICE AB The rat is a common laboratory animal utilized in a variety of investigations including experimental gerontology. Gerontologic investigations can be compromised when the differences observed when comparing young and old animals are actually differences between normal and disease states. It is of critical interest to know the pathology of the animals being studied and to understand the impact of these disease processes on the parameters being measured. The incidence and average age of occurrence for lesions have been characterized and are reported here for ane inbred (Brown Norway) and two hybrid strains (Brown Norway x Fischer 344 and Fischer 344 x Brown Norway) of rat. Total lesion incidence functions as a biomarker of aging for all of the strains examined (p less than or equal to .00001). These three genotypes have significantly lower incidence of several major pathologic processes (including glomerulonephritis, retinal atrophy, and leukemia) than do the Fischer 344 and the Wistar rats, two commonly utilized strains. Additionally, the BN and F344 x BN F-1 hybrid attain 50% mortality at 130 and 146 weeks of age, respectively, which is significantly greater than the 103 weeks for the F344 rat. It is hoped that access to basic information on these three rat genotypes will increase their utilization by the community of gerontologic scientists. C1 UNIV MICHIGAN,UNIT LAB ANIM MED,ANN ARBOR,MI 48109. NIA,BIOL AGING PROGRAM,BETHESDA,MD 20892. RP Lipman, RD (reprint author), TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,711 WASHINGTON ST,BOSTON,MA 02111, USA. FU NIA NIH HHS [N01-AG-7-2102, AG-077747]; PHS HHS [2555-1] NR 25 TC 153 Z9 155 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 1996 VL 51 IS 1 BP B54 EP B59 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TP043 UT WOS:A1996TP04300009 PM 8548501 ER PT J AU Schaefer, VI Talan, MI Shechtman, O AF Schaefer, VI Talan, MI Shechtman, O TI The effect of exercise training on cold tolerance in adult and old C57BL/6J mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID FISCHER 344 RATS; BROWN ADIPOSE-TISSUE; INDUCED THERMOGENESIS; EXHAUSTIVE EXERCISE; BODY-TEMPERATURE; SKELETAL-MUSCLE; AGE; STRESS; THERMOREGULATION; METABOLISM AB In order to ascertain the effect of aging on cross-adaptation between exercise training and cold tolerance, we studied cold tolerance in adult and old C57BL/6J male mice before and after 6 weeks of an exercise regimen of moderate intensity. There were two age groups of 32 mice each, including 12-month-old (adult) and 24-month-old (aged) mice equally divided into control and exercise groups. The exercise consisted of daily runs on a treadmill (1 hr/day, 5 days/week) for 6 weeks, while the control mice spent the same time on a stationary treadmill. All mice were subjected to a cold stress test (3-hr partial restraint at 6 degrees C) prior to and following the designated regimen. The results revealed a statistically significant interaction between age and exercise training. In adult mice, exercise resulted in a reduction of cold-induced heat production and weakening of cold tolerance, while in aged mice, the opposite effect was observed; i.e., an increase in cold-induced heat production accompanied by greater cold tolerance. However, only the attenuating effect on cold tolerance of adults was statistically significant. The results of our experiments do not support the existence of cross-adaptation between exercise training and cold tolerance. They indicate, however, that exercise training affects the cold tolerance in adult and old mice through different physiological mechanisms. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,BALTIMORE,MD 21224. UNIV FLORIDA,DEPT OCCUPAT THERAPY,GAINESVILLE,FL. NR 37 TC 10 Z9 10 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 1996 VL 51 IS 1 BP B38 EP B42 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TP043 UT WOS:A1996TP04300006 PM 8548498 ER PT J AU Mayuga, R Arrington, CT OConnor, FC Fleg, JL AF Mayuga, R Arrington, CT OConnor, FC Fleg, JL TI Why do exercise-induced ventricular arrhythmias increase with age? Role of M-mode echocardiographic aging changes SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID APPARENTLY HEALTHY-VOLUNTEERS; CORONARY-ARTERY DISEASE; HEART-DISEASE; HYPERTROPHY; HYPERTENSION; POPULATION; PREVALENCE; FREQUENT; ABSENCE; IMPACT AB Background. Although advancing age is associated with a higher prevalence and complexity of exercise-induced ventricular arrhythmias (EIVA), the role of age-associated cardiac anatomic and functional characteristics in this relationship has not been explored. Methods. We performed both M-mode echocardiography and maximal treadmill exercise testing within two consecutive visits in 366 healthy volunteers ages 20 to 90 years from the Baltimore Longitudinal Study of Aging. Results. Simple (i.e., isolated) EIVA were detected in 79 subjects (21%) and complex EIVA (i.e., EIVA comprising greater than or equal to 10% of beats in any minute or occurring in runs) in another 17 (5%). Univariate predictors of any EIVA, whether simple or complex, were older age (p < .0001), greater LV mass index (p < .0001), male gender (p < .001), higher peak exercise systolic blood pressure (p = .003), and larger body surface area (p = .005). By multiple logistic regression analysis, only age (p = .0001) independently predicted the occurrence of EIVA. For complex EIVA alone, the strongest univariate predictors were age (p = .004), male gender (p = .008), lower maximal heart rate (p = .01), greater left atrial size (p = .03), and larger LV posterior wall thickness (p = .04); on multiple logistic regression, only older age (p = .03) and larger left atrial size (p = .04) independently predicted the presence of complex EIVA. Conclusion. In healthy volunteers undergoing maximal treadmill exercise, greater LV wall thickness and mass are associated with the development of EIVA but they do not independently predict EIVA once the powerful effect of age is considered. The association between complex EIVA and left atrial dilatation may be mediated by higher LV end diastolic pressure and volume during exercise in subjects with larger left atria. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 32 TC 10 Z9 10 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 1996 VL 51 IS 1 BP M23 EP M28 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TP043 UT WOS:A1996TP04300020 PM 8548509 ER PT J AU Verbrugge, LM GruberBaldini, AL Fozard, JL AF Verbrugge, LM GruberBaldini, AL Fozard, JL TI Age differences and age changes in activities: Baltimore longitudinal study of aging SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the Gerontological-Society-of-America CY NOV, 1992 CL WASHINGTON, DC SP Gerontol Soc Amer ID DAILY LIFE; RETIREMENT; TIME AB This study examines cross-sectional age differences, longitudinal age changes, and secular changes in obligatory, committed, and discretionary activities, using activity questionnaires completed by men and women participants in the Baltimore Longitudinal Study of Aging between 1958 and 1992. (1) Time spent, on obligatory activities and passive leisure is greatest, and on committed activities and active leisure least, for older adults. (2) Longitudinal patterns usually mirror cross-sectional ones. There are pronounced exceptions for women whose paid work time has been increasing and housework decreasing, while cross-sectional patterns show the reverse. (3) Over recent decades, time in committed activities shifted in opposite ways for men and women. Men decreased paid work and increased housework, repairs and yardwork, shopping, and child-care, while women increased paid work and decreased housework. In sum, the age structure of activities has persisted in the midst of new social opportunities; gender roles have proven more malleable than age roles. C1 UNIV MARYLAND,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. NIA,GERONTOL RES CTR,LONGITUDINAL STUDIES BRANCH,BALTIMORE,MD 21224. RP Verbrugge, LM (reprint author), UNIV MICHIGAN,INST GERONTOL,300 N INGALLS,ANN ARBOR,MI 48109, USA. RI Fozard, James Leonard/B-3660-2009 FU NIA NIH HHS [T32 AG00114-07] NR 45 TC 80 Z9 80 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JAN PY 1996 VL 51 IS 1 BP S30 EP S41 PG 12 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA TP045 UT WOS:A1996TP04500010 PM 8548521 ER PT J AU Balow, JE Boumpas, DT Fessler, BJ Austin, HA AF Balow, JE Boumpas, DT Fessler, BJ Austin, HA TI Management of lupus nephritis SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 5th Annual North American Pediatric Renal Transplantation Cooperative Study CY APR 16-21, 1993 CL SAN FRANCISCO, CA ID CONTROLLED TRIAL; INTRAVENOUS CYCLOPHOSPHAMIDE; PULSE CYCLOPHOSPHAMIDE; THERAPY; PREDNISONE; ERYTHEMATOSUS; DRUGS RP Balow, JE (reprint author), NIDDK,KIDNEY DIS SECT,BLDG 10,ROOM 9N-222,BETHESDA,MD 20892, USA. NR 31 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 1996 VL 49 SU 53 BP S88 EP S92 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA TQ506 UT WOS:A1996TQ50600016 ER PT J AU Esposito, C Phillips, CL Liu, ZH Patel, A Striker, GE Striker, LJ AF Esposito, C Phillips, CL Liu, ZH Patel, A Striker, GE Striker, LJ TI Molecular analysis of human glomerular disease SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 5th Annual North American Pediatric Renal Transplantation Cooperative Study CY APR 16-21, 1993 CL SAN FRANCISCO, CA ID POLYMERASE CHAIN-REACTION; C VIRUS-INFECTION; RENAL-ALLOGRAFT REJECTION; MESSENGER-RNA; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; IV COLLAGEN; GLOMERULOSCLEROSIS; EXPRESSION; NEPHROPATHY; BIOPSY AB The development of molecular techniques has added a significant new dimension to the study of experimental pathology and of cellular biology of the kidney. Since the field is relatively new and many methods lack the sensitivity required for small fragments of tissue, there is very little data on renal biopsies [1]. In addition, ethical considerations have limited the amount of tissue that can be devoted to experimental techniques. These have combined to slow progress in understanding the molecular events underlying human renal diseases, but there has been recent clarification by a consensus conference [2]. This review will be restricted to DNA and mRNA detection in renal tissue. We will not consider genetic mutations, such as those present in Alport's disease, since the gene defect is present in all somatic cells and analysis can be performed with circulating cells. C1 NIDDK,RCBS,MDB,BETHESDA,MD 20892. NR 31 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 1996 VL 49 SU 53 BP S21 EP S25 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA TQ506 UT WOS:A1996TQ50600005 ER PT J AU Hijazi, Y Tsokos, M Steinberg, S Tzen, CY Horowitz, M Meyer, W Wexler, L Parham, D AF Hijazi, Y Tsokos, M Steinberg, S Tzen, CY Horowitz, M Meyer, W Wexler, L Parham, D TI Neuroectodermal differentiation does not play a role in the prognosis of Ewing's Sarcoma (ES) versus primitive neuroectodermal tumor (PNET) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 21 EP 21 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700052 ER PT J AU Zhuang, Z Bryant, B Pham, T Shelton, W Merino, MJ Chandra, R AF Zhuang, Z Bryant, B Pham, T Shelton, W Merino, MJ Chandra, R TI Identical genetic changes are detected in different components of Wilms' tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. CHILDRENS HOSP,DEPT PATHOL,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 42 EP 42 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75701102 ER PT J AU Quezado, M Middleton, LP Merino, MJ AF Quezado, M Middleton, LP Merino, MJ TI Epithelioid sarcomas: Prognostic factors and immunohistochemical profile SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 47 EP 47 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700078 ER PT J AU Quezado, M Zhuang, Z Middleton, LP Wang, C Bryant, B Lane, K Weiss, SW Merino, MJ AF Quezado, M Zhuang, Z Middleton, LP Wang, C Bryant, B Lane, K Weiss, SW Merino, MJ TI Detection of allelic loss in chromosome 22q in epithelioid sarcomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV MICHIGAN HOSP,ANN ARBOR,MI 48109. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 48 EP 48 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700079 ER PT J AU Chuaqui, R Zhuang, Z EmmertBuck, MR Liotta, L Merino, MJ AF Chuaqui, R Zhuang, Z EmmertBuck, MR Liotta, L Merino, MJ TI Genetic analysis of breast cancer precursor lesions using tissue microdissection and polymerase chain reaction SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,DEPT PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 72 EP 72 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700103 ER PT J AU Merino, MJ Middleton, LP Grases, P Tresserra, F AF Merino, MJ Middleton, LP Grases, P Tresserra, F TI Breast cancer and pregnancy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NATL CANC INST,BETHESDA,MD. INST DEXEUS,BARCELONA,SPAIN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 99 EP 99 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700130 ER PT J AU Middleton, LP Tressera, F Grases, P Merino, MJ AF Middleton, LP Tressera, F Grases, P Merino, MJ TI Infiltrating micropapillary carcinoma of the breast SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. INST DEXEUS,BARCELONA,SPAIN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 100 EP 100 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700131 ER PT J AU Zhuang, Z Nayar, R Merino, MJ Silverberg, SG AF Zhuang, Z Nayar, R Merino, MJ Silverberg, SG TI Loss of heterozygosity (LOH) on chromosome 11q13 in lobular lesions (ALH, LCIS, ILC) of the breast using tissue microdissection and polymerase chain reaction (PCR). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 139 EP 139 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700170 ER PT J AU Abati, A Jaffurs, W Wilder, AM Solomon, D AF Abati, A Jaffurs, W Wilder, AM Solomon, D TI Squamous atypia in the atrophic cervical vaginal smear. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 163 EP 163 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700194 ER PT J AU Chuaqui, R Vargas, MP Castiglioni, T Elsner, B Zhuang, Z EmmertBuck, MR Merino, MJ AF Chuaqui, R Vargas, MP Castiglioni, T Elsner, B Zhuang, Z EmmertBuck, MR Merino, MJ TI Detection of loss of heterozygosity (LOH) at chromosome 11Q13 in fine needle aspiration (FNA) of breast carcinomas using microdissection and polymerase chain reaction (PCR) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,DEPT PATHOL,BETHESDA,MD 20892. CEMIC,BUENOS AIRES,DF,ARGENTINA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 176 EP 176 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700207 ER PT J AU Xu, QB Ganju, L Fawcett, TW Holbrook, NJ AF Xu, QB Ganju, L Fawcett, TW Holbrook, NJ TI Vasopressin-induced heat shock protein expression in renal tubular cells SO LABORATORY INVESTIGATION LA English DT Article ID AGE-DEPENDENT RESPONSE; FACTOR-II; STRESS; EPINEPHRINE; ACTIVATION; INDUCTION AB Heat shock proteins (HSPs), which have been shown to be induced in the kidney by a variety of stress conditions, including ischemia, inflammation, oxidative stress, and toxin exposure, are believed to protect the cells from injury. In the present study, we demonstrated that administration of vasopressin iv. to Wistar rats leads to HSP70 induction in the kidney. The effect was specific to the kidney (ie., absent in brain, heart, lung, muscle, etc.) and selective for the HSP70 gene family (HSP27, HSP60, and HSP90 were not induced). Western blot analysis demonstrated that HSP70 protein expression peaked between 6 and 12 hours after vasopressin administration. Immunohistochemical staining revealed that induction was localized to renal tubule lining cells, with no expression seen in glomerular or interstitial regions. The elevated protein levels were preceded by the induction of HSP70 mRNA within 30 minutes after vasopression injection. The induction of HSP70 mRNA was associated with the activation of heat shock transcription factor 1 (HSF1), suggesting that the response was regulated at the level of transcription. This HSP70 expression was completely blocked in the presence of both a general vasopressin receptor antagonist (V-1 and V-2 receptors) and an antidiuretic antagonist (V-2), but not in the presence of a vasopressor antagonist (V-1). These observations could be significant for understanding the possible involvement of HSP70 in physiological processes of the kidney, as well as pathophysiologic conditions associated with either elevated or deficient levels of vasopressin. C1 NIA,SECT GENE EXPRESS & AGING,BALTIMORE,MD 21224. NR 40 TC 30 Z9 30 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 178 EP 187 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700019 PM 8569180 ER PT J AU Sgrignoli, A Abati, A AF Sgrignoli, A Abati, A TI Cytologic diagnosis of anaplastic large cell SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 201 EP 201 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700232 ER PT J AU Borkowski, A Berman, JJ Bennett, WP Jones, RT Harris, CC Kao, GF Trump, BF AF Borkowski, A Berman, JJ Bennett, WP Jones, RT Harris, CC Kao, GF Trump, BF TI Waf-1 growth suppressor gene activity in keratoacanthoma (KA) and squamous cell carcinoma (SCC) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 BALTIMORE VAMC,BALTIMORE,MD. UNIV MARYLAND,BALTIMORE,MD 21201. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 217 EP 217 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700248 ER PT J AU Hijazi, Y Fetsch, P Duray, P Cormier, J Marincola, F AF Hijazi, Y Fetsch, P Duray, P Cormier, J Marincola, F TI Immunocytochemical evaluation of a novel melanoma antibody, anti-MART-1 (M2-7, C10) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 230 EP 230 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700261 ER PT J AU Vargas, MP Zhuang, Z Wang, C Linehan, M Merino, MJ AF Vargas, MP Zhuang, Z Wang, C Linehan, M Merino, MJ TI Genetic alterations of sporadic pheochromocytoma are detected on the neuroblastoma and VHL disease gene locus SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 291 EP 291 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700322 ER PT J AU Vargas, MP Vargas, HI Kleiner, DE Merino, MJ AF Vargas, MP Vargas, HI Kleiner, DE Merino, MJ TI The role of prognostic markers (MIB 1, p53, RB and Bcl-2) in the diagnosis of parathyroid tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 292 EP 292 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700323 ER PT J AU Vargas, MP Kleiner, DE Merino, MJ AF Vargas, MP Kleiner, DE Merino, MJ TI The role of prognostic factors (MiB 1, p53 and RB) in the diagnosis of adrenocortical neoplasms (ACN) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 293 EP 293 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700324 ER PT J AU Zhuang, Z Debelenko, LV EmmertBuck, MR Dong, Q Chandrasekharappa, S Guru, SC Manickam, P Olufemi, ES Merino, MJ Spiegel, AM Marx, SJ Collins, FS Liotta, LA Lubensky, IA AF Zhuang, Z Debelenko, LV EmmertBuck, MR Dong, Q Chandrasekharappa, S Guru, SC Manickam, P Olufemi, ES Merino, MJ Spiegel, AM Marx, SJ Collins, FS Liotta, LA Lubensky, IA TI Chromosome 11q13 allelic deletions and X chromosome inactivation analysis of tumors in patients with MEN 1 SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,NIDDK,NCHGR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 294 EP 294 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700325 ER PT J AU Roth, M Liu, S Solomon, D Zhou, B Copeland, C Wang, G Dawsey, S AF Roth, M Liu, S Solomon, D Zhou, B Copeland, C Wang, G Dawsey, S TI Esophageal cytology and the Bethesda system in China SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,DCPC,BETHESDA,MD. NCI,LP,BETHESDA,MD. CHINESE ACAD MED SCI,INST CANC,BEIJING,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 363 EP 363 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700394 ER PT J AU AlboresSaavedra, J Ashfaq, R Henson, DE AF AlboresSaavedra, J Ashfaq, R Henson, DE TI Carcinoid and small cell carcinoma of the uterine cervix SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 499 EP 499 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700530 ER PT J AU Chuaqui, R Nogales, F Merino, MJ AF Chuaqui, R Nogales, F Merino, MJ TI The spectrum of histologic changes in atypical polypoid adenomyoma of the uterus SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,DEPT PATHOL,BETHESDA,MD 20892. UNIV GRANADA,GRANADA,SPAIN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 506 EP 506 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700537 ER PT J AU Kussick, SJ Chang, K Pastan, I Gown, AM AF Kussick, SJ Chang, K Pastan, I Gown, AM TI Monoclonal antibody K1 is a highly sensitive and relatively specific marker for papillary serous ovarian carcinoma in deparaffinized, formalin-fixed tissue. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 UNIV WASHINGTON,SEATTLE,WA 98195. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 537 EP 537 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700568 ER PT J AU Silva, E Tornos, C Zhuang, M Merino, M Gershenson, D AF Silva, E Tornos, C Zhuang, M Merino, M Gershenson, D TI Tumor recurrence in stage I ovarian serous low malignant potential neoplasms. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 565 EP 565 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700596 ER PT J AU ElenitobaJohnson, KSJ Medeiros, LJ Khorsand, J King, TC AF ElenitobaJohnson, KSJ Medeiros, LJ Khorsand, J King, TC TI p53 overexpression in Hodgkin's disease is correlated with mutation or MDM-2 expression SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. CITY HOPE NATL MED CTR,DUARTE,CA 91010. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 643 EP 643 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700674 ER PT J AU ElenitobaJohnson, KSJ Khorsand, J Medeiros, LJ Gelb, A King, TC AF ElenitobaJohnson, KSJ Khorsand, J Medeiros, LJ Gelb, A King, TC TI Mutational analysis of p53 and Ras oncogenes in solitary plasmacytomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA. CITY HOPE NATL MED CTR,DUARTE,CA 91010. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 644 EP 644 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700675 ER PT J AU Kaldjian, EP Jaffe, ES Shaw, S AF Kaldjian, EP Jaffe, ES Shaw, S TI Immunohistochemical characterization of the lymph node reticular network: Implications for intra-nodal information transfer and stromal proliferation SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 661 EP 661 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700692 ER PT J AU Kamel, OW Weiss, LM vandeRijn, M Kingma, DW Jaffe, ES AF Kamel, OW Weiss, LM vandeRijn, M Kingma, DW Jaffe, ES TI Hodgkin's disease and Hodgkin's disease-like large cell lymphomas in patients receiving long-term low-dose methotrexate therapy SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 STANFORD UNIV,MED CTR,STANFORD,CA 94305. CITY HOPE NATL MED CTR,DUARTE,CA 91010. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 662 EP 662 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700693 ER PT J AU Krenacs, L Raffeld, M Jaffe, ES AF Krenacs, L Raffeld, M Jaffe, ES TI Cytotoxic cell-related antigen expression in anaplastic large cell lymphoma (ALCL) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. RI Krenacs, Laszlo/L-8063-2014 OI Krenacs, Laszlo/0000-0001-6541-3031 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 666 EP 666 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700697 ER PT J AU Kumar, S Otsuki, T Kumar, D Harris, CA Wellmann, A Jaffe, ES Raffeld, M AF Kumar, S Otsuki, T Kumar, D Harris, CA Wellmann, A Jaffe, ES Raffeld, M TI BCL-1 rearrangement in multiple lymphomatous polyposis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,HEMATOPATHOL SECT,BETHESDA,MD 20892. UNIV MARYLAND,MED SYST,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 668 EP 668 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700699 ER PT J AU Kumar, S Green, GA TeruyaFeldstein, J Raffeld, M Jaffe, ES AF Kumar, S Green, GA TeruyaFeldstein, J Raffeld, M Jaffe, ES TI Utility of CD23 (BU38) immunostaining on fixed tissue sections in the differential diagnosis between small lymphocytic lymphoma and mantle cell lymphoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,HEMATOPATHOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 669 EP 669 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700700 ER PT J AU Lim, MS StetlerStevenson, M Straus, SE Sneller, MC Dale, JK Strober, W Jaffe, ES AF Lim, MS StetlerStevenson, M Straus, SE Sneller, MC Dale, JK Strober, W Jaffe, ES TI Pathology of human autoimmune lymphoproliferative syndrome associated with fas gene mutations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 671 EP 671 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700702 ER PT J AU Marmaduke, DP Rosai, J Warnke, R Foucar, K EmmertBuck, MR Liotta, LA Willman, CL AF Marmaduke, DP Rosai, J Warnke, R Foucar, K EmmertBuck, MR Liotta, LA Willman, CL TI Molecular assessment of clonality in sinus histiocytosis with massive lymphadenopathy (SHML): A reactive disorder of polyclonal histocytes SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 UNIV NEW MEXICO,SCH MED,ALBUQUERQUE,NM 87131. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. STANFORD UNIV,STANFORD,CA 94305. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 677 EP 677 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700708 ER PT J AU Alonsozana, ELC Abruzzo, LV Kumar, D Frantz, C Kingma, DW Sun, CCJ AF Alonsozana, ELC Abruzzo, LV Kumar, D Frantz, C Kingma, DW Sun, CCJ TI Epstein-Barr virus associated leiomyosarcomas in a child with AIDS. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,DEPT PEDIAT,BALTIMORE,MD 21201. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 743 EP 743 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700774 ER PT J AU Lash, A EmmertBuck, M Merino, MJ Liotta, L Zhuang, ZP AF Lash, A EmmertBuck, M Merino, MJ Liotta, L Zhuang, ZP TI Identification of Kaposi's sarcoma-associated herpes-like virus in Kaposi's sarcoma lesions from archival material using microdissection and PCR amplification SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 756 EP 756 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700787 ER PT J AU Shieh, WJ Ksaizek, T Bethke, FR Greer, PW Zaki, SR AF Shieh, WJ Ksaizek, T Bethke, FR Greer, PW Zaki, SR TI Immunohistochemical diagnosis of flavivirus infection in paraffin-embedded human tissues SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. BCDP,SAIC,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 764 EP 764 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700795 ER PT J AU Przygodzki, RM Finkelstein, SD Keohavong, P Bakker, A Swalsky, PA Soini, Y Ishak, KG Bennett, WP AF Przygodzki, RM Finkelstein, SD Keohavong, P Bakker, A Swalsky, PA Soini, Y Ishak, KG Bennett, WP TI Sporadic and thorotrast-induced angiosarcomas of the liver manifest a high rate and multiple point mutations in K-ras-2 SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 ARMED FORCES INST PATHOL,DEPT PULM PATHOL,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT HEPAT PATHOL,WASHINGTON,DC 20306. UNIV PITTSBURGH,MED CTR,DEPT PATHOL,PITTSBURGH,PA. GRAD SCH PUBL HLTH,PITTSBURGH,PA. NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 793 EP 793 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700824 ER PT J AU Vortmeyer, AO Zhuang, Z Gnarra, JR EmmertBuck, M Katz, D Linehan, WM Oldfield, EH AF Vortmeyer, AO Zhuang, Z Gnarra, JR EmmertBuck, M Katz, D Linehan, WM Oldfield, EH TI Genetic changes in cerebellar hemangioblastomas associated with von Hippel-Lindau disease SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NIH,NCI,NINDS,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 813 EP 813 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700844 ER PT J AU Kotoula, V Tsokos, M AF Kotoula, V Tsokos, M TI Loss of heterozygosity in nerve sheath tumors (NST) at the CRYB2 locus SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 821 EP 821 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700852 ER PT J AU Beckner, ME Liotta, LA AF Beckner, ME Liotta, LA TI Modulation of endothelial cell formation of capillary-like tubes by AAMP and heparin SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NATL CANC INST,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 835 EP 835 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700866 ER PT J AU Neuenschwander, S Schwartz, AM Wood, TL Roberts, CT Henninghausen, L LeRoith, D AF Neuenschwander, S Schwartz, AM Wood, TL Roberts, CT Henninghausen, L LeRoith, D TI IGF-1 modulates involution of the lactating mammary gland in a transgenic mouse model SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,WASHINGTON,DC. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 864 EP 864 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700895 ER PT J AU Lash, A Beaty, M Kleiner, D Zhuang, ZP AF Lash, A Beaty, M Kleiner, D Zhuang, ZP TI Pneumocystis carinii DNA identified in a spleen showing dystrophic calcification and sclerosis of white pulp in a pediatric HIV+ patient SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 880 EP 880 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700911 ER PT J AU Quezado, M Gosnay, R Abaza, M Tsokos, M AF Quezado, M Gosnay, R Abaza, M Tsokos, M TI The value of EWS-FLI1/ERG transcripts and 12E7 in the diagnosis of Ewing's sarcoma family (ESF) of tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 887 EP 887 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700918 ER PT J AU Quezado, M Toskos, M AF Quezado, M Toskos, M TI Detection of the PAX3/FKHR fusion transcript in solid alveolar rhabdomyosarcoma (RMS) by RT-PCR SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 888 EP 888 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700919 ER PT J AU Tsokos, M Szentendrei, T Vassilopoulos, D Quezado, M Kovacs, B Karameris, A Tsokos, G AF Tsokos, M Szentendrei, T Vassilopoulos, D Quezado, M Kovacs, B Karameris, A Tsokos, G TI Fas-mediated apoptosis in peripheral primitive neuroectodermal tumor (PNET) Ewing's sarcoma (ES) cell lines SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. RES INST,WASHINGTON,DC. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 890 EP 890 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700921 ER PT J AU Abati, A Sanford, J Fetsch, P Pass, H AF Abati, A Sanford, J Fetsch, P Pass, H TI Detection of aneuploidy in mesothelioma cell lines by fluorescence in situ hybridization (FISH) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 893 EP 893 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700924 ER PT J AU Bennett, WP ElDeiry, WS Guinee, DG Caporaso, NE Welsh, JA Jones, RT Borkowski, A Travis, WD Colby, TV Trastek, V Pairolero, PC Tazelaar, HF Midthun, D Jett, JR Liotta, LA Vogelstein, B Harris, CC AF Bennett, WP ElDeiry, WS Guinee, DG Caporaso, NE Welsh, JA Jones, RT Borkowski, A Travis, WD Colby, TV Trastek, V Pairolero, PC Tazelaar, HF Midthun, D Jett, JR Liotta, LA Vogelstein, B Harris, CC TI p53/p21((waf1/cip1)) expression in human lung cancer SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. NCI,BETHESDA,MD 20892. UNIV UTAH,MED CTR,SALT LAKE CITY,UT. UNIV MARYLAND,BALTIMORE,MD 21201. BALTIMORE VA MED CTR,BALTIMORE,MD. ARMED FORCES INST PATHOL,WASHINGTON,DC. MAYO CLIN SCOTTSDALE,SCOTTSDALE,AZ. MAYO CLIN,ROCHESTER,MN. PITTSBURGH CANC CTR,PITTSBURGH,PA. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 895 EP 895 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700926 ER PT J AU Fleming, MV Falk, R Przygodzki, R Zhang, J Bennett, WP Travis, WD Colby, TV Jett, J Tazelaar, H Trastek, V Pairolero, P Liotta, LA Caporaso, NE Ferrans, VJ Harris, CC AF Fleming, MV Falk, R Przygodzki, R Zhang, J Bennett, WP Travis, WD Colby, TV Jett, J Tazelaar, H Trastek, V Pairolero, P Liotta, LA Caporaso, NE Ferrans, VJ Harris, CC TI Gender, age, and environmental exposures are associated with increased apoptosis in non-small-cell (NSC) lung carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NHLBI,DIV INTRAMURAL RES,BETHESDA,MD 20892. MAYO CLIN,ROCHESTER,MN 55905. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 904 EP 904 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700935 ER PT J AU Guinee, DG Fleming, M Hayashi, T Woodward, M Zhang, J Koss, M Ferrans, V Travis, W AF Guinee, DG Fleming, M Hayashi, T Woodward, M Zhang, J Koss, M Ferrans, V Travis, W TI Association of p53 and Waf1 expression with DNA damage and apoptosis in diffuse alveolar damage. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 UNIV UTAH,DEPT PATHOL,SALT LAKE CITY,UT. AFIP,DEPT PULM & MEDIASTINAL PATHOL,WASHINGTON,DC. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 914 EP 914 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700945 ER PT J AU Hayashi, T Fleming, MV StetlerStevenson, WG Liotta, LA Moss, J Ferrans, VJ Travis, WD AF Hayashi, T Fleming, MV StetlerStevenson, WG Liotta, LA Moss, J Ferrans, VJ Travis, WD TI Immunohistochemical study of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pulmonary lymphangioleiomyomatosis (LAM) SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 916 EP 916 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700947 ER PT J AU Horiba, K Fukuda, Y StetlerStevenson, WG Liotta, LA Ferrans, VJ AF Horiba, K Fukuda, Y StetlerStevenson, WG Liotta, LA Ferrans, VJ TI Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) during rat tracheal wound healing SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NIPPON MED COLL,TOKYO,JAPAN. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 917 EP 917 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700948 ER PT J AU Jensen, SM Linnoila, RI AF Jensen, SM Linnoila, RI TI The pathology of bronchiolization of the alveoli: Progressive changes during human lung carcinogenesis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 919 EP 919 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700950 ER PT J AU Przygodzki, RM Caporaso, NE Bennett, WP Travis, WD Colby, TV Jett, J Tazelaar, H Pairolero, P Trastek, V Liotta, LA Harris, CC AF Przygodzki, RM Caporaso, NE Bennett, WP Travis, WD Colby, TV Jett, J Tazelaar, H Pairolero, P Trastek, V Liotta, LA Harris, CC TI K-ras-2 mutations in subjects with lung carcinoma in the NCI-Mayo lung cancer study SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,PULM PATHOL DEPT,WASHINGTON,DC 20306. MAYO CLIN,ROCHESTER,MN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 946 EP 946 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700977 ER PT J AU Raja, KN Khan, MA Jones, RT Borkowski, A Bennett, WP AF Raja, KN Khan, MA Jones, RT Borkowski, A Bennett, WP TI p53 protein is stable after storage at room temperature for 2-5 years: Analysis of human tumor sections of lung, esophagus and head & neck SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV MARYLAND,BALTIMORE,MD 21201. BALTIMORE VA HOSP,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 948 EP 948 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75700979 ER PT J AU Beckner, ME Krutzsch, HC Liotta, LA AF Beckner, ME Krutzsch, HC Liotta, LA TI A new alpha-actinin antibody is specific for an assembled epitope that is shared with AAMP SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 994 EP 994 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75701025 ER PT J AU Fest, T Wellmann, A Quezado, M Gosnay, R Tsokos, M Jaffe, ES Raffeld, M AF Fest, T Wellmann, A Quezado, M Gosnay, R Tsokos, M Jaffe, ES Raffeld, M TI A comparative study of DGGE and SSCP for assessing p53 mutations SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 1003 EP 1003 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75701034 ER PT J AU Geradts, J Kratzke, RA Niehans, GA Birrer, MJ Olshan, AF AF Geradts, J Kratzke, RA Niehans, GA Birrer, MJ Olshan, AF TI Immunohistochemical evaluation of tumor suppressor gene products pRB and p16 in routinely processed human tumors SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC. VET ADM MED CTR,MINNEAPOLIS,MN. NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1996 VL 74 IS 1 BP 1005 EP 1005 PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA TT757 UT WOS:A1996TT75701036 ER PT B AU Dean, M AF Dean, M BE Landegren, U TI SSCP and heteroduplex analysis SO LABORATORY PROTOCOLS FOR MUTATION DETECTION LA English DT Proceedings Paper CT 3rd International Workshop on Mutation Detection - Mutation Detection 1995 CY MAY 18-21, 1995 CL VISBY, SWEDEN SP Human Genome Org C1 NCI,FREDERICK CANC RES & DEV FAC,FREDERICK,MD 21702. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI NEW YORK PA 198 MADISON AVENUE, NEW YORK, NY 10016 BN 0-19-857795-8 PY 1996 BP 23 EP 26 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BF52N UT WOS:A1996BF52N00005 ER PT J AU Holzer, SES Ludlow, CL AF Holzer, SES Ludlow, CL TI The swallowing side effects of botulinum toxin type A injection in spasmodic dysphonia SO LARYNGOSCOPE LA English DT Article ID SPASTIC DYSPHONIA; SPEECH AB Botulinum toxin type A (BOTOX (R)) injection of the thyroarytenoid muscle is used to control speech symptoms in patients with adductor spasmodic dysphonia. Transient difficulty in swallowing liquids is a common treatment side effect. Laryngeal movement durations were measured during swallowing in 13 adductor spasmodic dysphonia patients undergoing treatment and in 6 normal control subjects in order to determine the following: 1. whether, prior to the injection, laryngeal movement durations were longer in the spasmodic dysphonia patients than in the control subjects; 2. whether movement durations increased following the injections; 3. whether preinjection swallowing difficulties related to postinjection swallowing measurements and postinjection patient reports of swallowing problems. A piezoelectric movement transducer was shown to be accurate for noninvasive measurement of laryngeal movement duration in relation to muscle onset and offset for hyoid elevation and relaxation. Before botulinum toxin type A injection, no significant differences in swallowing duration were found between the patient and control groups. Pour patients with swallowing complaints prior to injection had longer laryngeal movement durations than the other spasmodic dysphonia patients and the control subjects. Following injection, laryngeal movement durations increased in the patients with spasmodic dysphonia, and eight patients reported dysphagia for an average of 2 weeks. Relationships were found between the patients' initial reports of swallowing problems and increased laryngeal movement durations before and after botulinum toxin type A injection. Those patients initially reporting swallowing difficulties had severe dysphagia for 2 weeks after the injection. Patient reports of dysphagia prior to injection may indicate a greater likelihood of significant dysphagia following thyroarytenoid injection with botulinum toxin type A. C1 NATL INST DEAFNESS & OTHER COMMUN DISORDERS,VOICE & SPEECH SECT,BETHESDA,MD 20892. OI Ludlow, Christy/0000-0002-2015-6171 NR 20 TC 18 Z9 18 U1 4 U2 13 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JAN PY 1996 VL 106 IS 1 BP 86 EP 92 PN 1 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA TN814 UT WOS:A1996TN81400017 PM 8544635 ER PT J AU Poppas, DP Massicotte, JM Stewart, RB Roberts, AB Atala, A Retik, AB Freeman, MR AF Poppas, DP Massicotte, JM Stewart, RB Roberts, AB Atala, A Retik, AB Freeman, MR TI Human albumin solder supplemented with TGF-beta(1) accelerates healing following laser welded wound closure SO LASERS IN SURGERY AND MEDICINE LA English DT Article ID FIBROBLAST GROWTH-FACTOR; PROTEIN SOLDER; REPAIR; MODEL; SKIN; BETA; EGF AB Background and Objective: We examined the possibility that human albumin solder can be used as a vehicle for site specific delivery of growth factors for the purpose of accelerating tissue repair following laser welded wound closure. Certain human recombinant growth factors have been shown to accelerate wound healing in model systems. Pilot in vitro studies have established that several growth factors, including TGF-beta(1), maintain bioactivity following exposure to temperatures achieved during laser tissue welding. Using a temperature controlled laser delivery system (TCL) to precisely maintain welding temperatures, it is now possible to avoid thermal denaturation of exogenous bioactive molecules such as growth factors. Study Design/Materials and Methods: HB-EGF, bFGF, and TGF-beta(1) were tested in vitro for maintenance of bioactivity after exposure to 80 degrees C. In vivo experiments using porcine skin determined the efficacy of solders augmented with growth factors. Incisions were repaired using human albumin alone or supplemented with HB-EGF (2 mu g), bFGF (10 mu g), or TGF-beta(1) (1 mu g). Wounds were excised at 3, 5, and 7 days post-operatively. Tensile strength, total collagen content, and histology were performed. Results: At 3 days, tensile strength (TS) of TGF-beta(1) wounds were 36% (P < 0.05) and 20% (n.s.) stronger than laser alone and suture closures, respectively. By 5 days the TS of the TGF-beta(1) group increased by 50% (P < 0.05) and 59% (P < 0.02) over laser alone and suture groups, respectively. At 7 days the TGF-beta(1) group was 50% (P < 0.05) and 79% (P < 0.01) stronger than laser solder alone or suture, respectively. The HB-EGF and bFGF groups were equivalent to the laser solder group at all time points. Total collagen content at 7 days increased in the TGF-beta(1) group by 7% (n.s.) over the suture group and 21% (P < 0.05) in the laser group. Conclusion: Human albumin solder supplemented with TGF-beta(1) increases the early post-operative strength of laser welded wounds. This novel application of laser tissue soldering augmented with a growth factor has the potential to bring about immediate fluid tight seals while providing site specific delivery of biological modifiers. This may lead to an overall improvement in post-operative convalescence, wound infections, and hospital costs. C1 HARVARD UNIV, CHILDRENS HOSP, SCH MED, DEPT SURG, DIV UROL, BOSTON, MA 02115 USA. ABIOMED R&D INC, DANVERS, MA 01923 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. RP Poppas, DP (reprint author), CORNELL UNIV, NEW YORK HOSP,DEPT UROL,MED CTR,DIV PEDIAT UROL, JAMES BUCHANAN BRADY FDN, NEW YORK, NY 10021 USA. OI Atala, Anthony/0000-0001-8186-2160 FU NIDDK NIH HHS [R41DK50505-01] NR 33 TC 51 Z9 52 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PY 1996 VL 19 IS 3 BP 360 EP 368 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA VR669 UT WOS:A1996VR66900013 PM 8923433 ER PT B AU Shih, JH Louis, TA AF Shih, JH Louis, TA BE Jewell, NP Kimber, AC Lee, MLT Whitmore, GA TI Assessing gamma frailty models for clustered failure time data SO LIFETIME DATA: MODELS IN RELIABILITY AND SURVIVAL ANALYSIS LA English DT Proceedings Paper CT 1994 International Research Conference on Lifetime Data Models in Reliability and Survival Analysis CY JUN 15-17, 1994 CL HARVARD UNIV, CAMBRIDGE, MA SP Amer Stat Assoc, Boston Chapter, Harvard Univ, Stat Dept, Channing Lab, Brigham & Womens Hosp, Harvard Med Sch, Kluwer Acad Publ, Pfizer Inc HO HARVARD UNIV AB Proportional hazards frailty models use a random effect, so called frailty, to construct association for clustered failure time data. It is customary to assume that the random frailty follows a gamma distribution. In this paper, we propose a graphical method for assessing adequacy of the proportional hazards frailty models. In particular, we focus on the assessment of the gamma distribution assumption for the frailties. We calculate the average of the posterior expected frailties at several followup time points and compare it at these time points to 1, the known mean frailty. Large discrepancies indicate lack of fit. To aid in assessing the goodness of fit, we derive and estimate the standard error of the mean of the posterior expected frailties at each time point examined. We give an example to illustrate the proposed methodology. RP Shih, JH (reprint author), NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-3783-2 PY 1996 BP 299 EP 305 PG 7 WC Statistics & Probability SC Mathematics GA BH17J UT WOS:A1996BH17J00039 ER PT J AU Ward, G Woods, J Reyzer, M Salem, N AF Ward, G Woods, J Reyzer, M Salem, N TI Artificial rearing of infant rats on milk formula deficient in n-3 essential fatty acids: A rapid method for the production of experimental n-3 deficiency SO LIPIDS LA English DT Article; Proceedings Paper CT Symposium on Dietary Fat and Neural Development, at the AOCS Annual Meeting and Expo CY MAY 07-11, 1995 CL SAN ANTONIO, TX SP AOCS, Wyeth Ayerst, Mead Johnson, Martek Biosci, Nestle, Ross Labs ID ALPHA-LINOLENIC ACID; RHESUS-MONKEYS; BRAIN; GROWTH; DIET; SUBSTITUTES; MEMBRANES; ACCRETION; BEHAVIOR; FEMALE AB Research into the function of docosahexaenoic acid (DHA; 22:6n-3), the predominant polyunsaturated fatty acid (PUFA) in the central nervous system (CNS), is often hindered by the difficulty in obtaining dramatic experimental decreases in DHA in the brain and retina of laboratory rats. In this study, the artificial rearing procedure, whereby infant rats are removed from their mothers, gastrostomized, and fed synthetic formula, was used in an attempt to produce rapid changes in CNS levels of DHA. Female rats were raised, from day 4-5 of life, on one of two formulas-one containing the essential fatty acids of both the n-6 and n-3 series in proportions approximately equal to those of rat milk, and the other containing high levels of 18.2n-6 but very little n-3 fatty acid. At weaning, both groups were given A1N-76A diets modified so that the PUFA content resembled that of the preweaning formula. At eight weeks of age, the n-3-deficient group exhibited decreases of more than 50% in total DHA content in the brain, accompanied by increases in arachidonic acid (AA) (20:4n-6) and, especially, docosapentaenoic acid (22:5n-6). Other artificially-reared rats were mated and their offspring were also maintained on the respective diets. in spite of the fact that they had been reared artificially, the rats mated successfully and reared litters with no obvious abnormalities. At both ten days of age and again at eight weeks, offspring of the n-3-deficient mothers exhibited decreases of more than 90% in total DHA content. Again, the long-chain n-6 PUFA increased proportionately so that total PUFA levels in the brain were not lower. As these differences are greater than those commonly reported, even after 2-3 generations of normal dietary deprivation in rodents, this procedure may be an important tool in the study of the effects of n-3 deficiency on neural development and, subsequently, of the function of DHA in nervous tissue. C1 NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,ROCKVILLE,MD 20852. NR 37 TC 49 Z9 50 U1 0 U2 2 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD JAN PY 1996 VL 31 IS 1 BP 71 EP 77 DI 10.1007/BF02522414 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA TP733 UT WOS:A1996TP73300012 PM 8649237 ER PT J AU Bizzi, A Righini, A Turner, R leBihan, D Bockhorst, KH Alger, JR AF Bizzi, A Righini, A Turner, R leBihan, D Bockhorst, KH Alger, JR TI Imaging focal reperfusion injury following global ischemia with diffusion-weighted magnetic resonance imaging and H-1-magnetic resonance spectroscopy SO MAGNETIC RESONANCE IMAGING LA English DT Article DE cerebral ischemia; proton magnetic resonance spectroscopy; magnetic resonance imaging; diffusion; reperfusion ID ACUTE CEREBRAL-ISCHEMIA; ACUTE HUMAN STROKE; CARDIAC-ARREST; WATER DIFFUSION; NMR-SPECTROSCOPY; BRAIN ISCHEMIA; RAT-BRAIN; CAT BRAIN; MR; ENERGY AB The purpose of the study was to determine whether diffusion-weighted magnetic resonance imaging (DWI) could identify focal lesions that develop in ischemia-sensitive cerebral tissues during reperfusion following global brain ischemia, Localized H-1-Magnetic Resonance Spectroscopy (H-1-MRS) measurements were also obtained to determine whether abnormal spectroscopic markers were associated with focal lesions and to define time correlations between DWI and metabolic changes, Brain diffusion-weighted magnetic resonance imaging measurements were made in a cat model of repetitive global cerebral ischemia and reperfusion, Five animals were exposed to three episodes of 10 min vascular occlusions at hourly intervals, Three animals were evaluated as controls, DWI, T2WI, and H-1-MRS data were acquired for up to 12 h. Transient focal DWI hyperintensity was detected in the hippocampus, basal ganglia, and cortical watershed areas, These focal abnormalities usually appeared during the final reperfusion and eventually spread to encompass all of the gray matter, Spectroscopic measurements demonstrated the expected elevation of the lactate signal intensity during vessel occlusion, which returned to normal during early reperfusion, A subsequent rise in the lactate signal occurred approximately 3-4 h after the beginning of the third reperfusion, This late lactate elevation occurred after focal hyperintensities were identified by DWI, No significant signal changes were seen in spectroscopic metabolites other than lactate. The study illustrates that DWI and H-1-MRS are sensitive to focal cerebral lesions that occur during reperfusion following global cerebral ischemia. C1 NINCDS, NEUROIMAGING BRANCH, NIH, BETHESDA, MD 20892 USA. RI Turner, Robert/C-1820-2008; Bizzi, Alberto/K-3141-2016 OI Bizzi, Alberto/0000-0002-0253-5274 NR 63 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X EI 1873-5894 J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PY 1996 VL 14 IS 6 BP 581 EP 592 DI 10.1016/0730-725X(96)00094-X PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VL874 UT WOS:A1996VL87400002 PM 8897360 ER PT J AU Rajapakse, JC Giedd, JN DeCarli, C Snell, JW McLaughlin, A Vauss, YC Krain, AL Hamburger, S Rapoport, JL AF Rajapakse, JC Giedd, JN DeCarli, C Snell, JW McLaughlin, A Vauss, YC Krain, AL Hamburger, S Rapoport, JL TI A technique for single-channel MR brain tissue segmentation: Application to a pediatric sample SO MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; brain imaging; white matter; gray matter; cerebrospinal fluid; region growing ID MAGNETIC-RESONANCE IMAGES; GRAY-MATTER; CLASSIFICATION; MORPHOMETRY; WHITE; CSF; LOCALIZATION; VALIDATION; MORPHOLOGY; VOLUMES AB A segmentation method is presented for gray matter, white matter, and cerebrospinal fluid (CSF) in thin-sliced single-channel brain magnetic resonance (MR) scans, The method is based on probabilistic modeling of intensity distributions and on a region growing technique, Interrater and intrarater reliabilities for the method were high, and comparison with phantom studies and hand-traced results from an experienced rater indicated good validity, The method was designed to account for spatially dependent image intensity inhomogeneities. Segmentation of MR brain scans of 105 (56 male and 49 female) healthy children and adolescents showed that although the total brain volume was stable over age 4-18, white matter increased and gray matter decreased significantly. There were no sex differences in total gray and white matter growth after correction for total brain volume. White matter volume increased the most in superior and posterior regions and laterality effects were seen in hemisphere tissue volumes. These findings are consistent with other reports, and further validate the segmentation technique. 1996 Elsevier Science Inc. RP Rajapakse, JC (reprint author), NIMH, CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR, MSC 1600, BETHESDA, MD 20892 USA. RI Giedd, Jay/A-3080-2008; DeCarli, Charles/B-5541-2009; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 44 TC 24 Z9 24 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PY 1996 VL 14 IS 9 BP 1053 EP 1065 DI 10.1016/S0730-725X(96)00113-0 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA WG847 UT WOS:A1996WG84700007 PM 9070996 ER PT J AU Kanthimathi, T Hughes, L Subramanian, S AF Kanthimathi, T Hughes, L Subramanian, S TI The solution structure of TRH - A H-1 NMR reinvestigation SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE NMR; H-1 NMR; TRH; molecular mechanics; 2D COSY; rotamer populations AB High-resolution H-1 NMR and molecular mechanics calculations were used to evaluate the solution structure of TRH (pyroglutamic acid-histidine-prolinamide). The results indicate that there are only two rotamers present at room temperature with a sufficient energy barrier on the 400 MHz NMR time-scale to be well resolved, These are in the ratio of ca. 9:1. A time-averaged single conformer was obtained when the NMR experiment was carried out at 90 degrees C. A two-dimensional COSY experiment further confirmed the presence of only two rotamers, Molecular mechanics calculations predict the presence of three rotamers, although statistically only two of them will be populated in the ratio of 95:5 at room temperature. Very little secondary structure was indicated from a 2D NOESY experiment and it is concluded that TRH adapts an extended and not a 'hairpin' structure. The 1:1 Li-TRH adduct also exhibits the presence of the same rotamers, although lithium binding is evidenced by a downfield shift of histidine NH resonances in both rotamers to the same extent of 80 Hz. C1 INDIAN INST TECHNOL,DEPT CHEM,MADRAS 600036,TAMIL NADU,INDIA. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. NR 20 TC 0 Z9 0 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD JAN PY 1996 VL 34 IS 1 BP 83 EP 88 DI 10.1002/(SICI)1097-458X(199601)34:1<83::AID-OMR818>3.0.CO;2-0 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA TP235 UT WOS:A1996TP23500015 ER PT J AU Vymazal, J Brooks, RA Baumgarner, C Tran, V Katz, D Bulte, JWM Bauminger, ER DiChiro, G AF Vymazal, J Brooks, RA Baumgarner, C Tran, V Katz, D Bulte, JWM Bauminger, ER DiChiro, G TI The relation between brain iron and NMR relaxation times: An in vitro study SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE brain iron; ferritin; T-2 shortening; T-i ID DIFFERENT FIELD STRENGTHS; FERRITIN; MR; TISSUE; T2 AB T-1 and T-2 relaxation times and iron concentrations were measured in 24 specimens of gray matter from fresh human and monkey brains at magnetic fields from 0.05 to 1.5 Tesla, Three different effects were found that correlate with iron content: a T-1-shortening that falls off somewhat at high fields, a T-2-shortening that is field-independent and thus important at low fields, and a contribution to 1/T-2 that increases linearly with field strength, This linear field dependence has been seen only in ferritin and other ferric oxyhydroxide particles, Our results are in agreement with in vivo MRI studies and are generally consistent with values for ferritin solution, except for differences such as clustering of ferritin in tissue, A cerebral cavernous hemangioma specimen showed similar T-2-shortening, but with a 2.7 times larger magnitude, attributed to larger clusters of hemosiderin in macrophages, The dependence on interecho time 2 tau was measured in three brains; 1/T-2 increased significantly for tau up to 32 ms, as expected from the size of the ferritin clusters, These findings support the theory that ferritin iron is the primary determinant of MRI contrast in normal gray matter. C1 NATL INST HLTH, NINDS, NEUROIMAGING BRANCH, BETHESDA, MD 20892 USA. NATL INST HLTH, NINDS, OFF CLIN DIRECTOR, BETHESDA, MD 20892 USA. NATL INST HLTH, NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NATL INST HLTH, OFF DIRECTOR, LAB DIAGNOST RADIOL RES, BETHESDA, MD 20892 USA. HEBREW UNIV JERUSALEM, RACAH INST PHYS, IL-91904 JERUSALEM, ISRAEL. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 15 TC 121 Z9 122 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 1996 VL 35 IS 1 BP 56 EP 61 DI 10.1002/mrm.1910350108 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TN368 UT WOS:A1996TN36800007 PM 8771022 ER PT J AU Pekar, J Jezzard, P Roberts, DA Leigh, JS Frank, JA McLaughlin, AC AF Pekar, J Jezzard, P Roberts, DA Leigh, JS Frank, JA McLaughlin, AC TI Perfusion imaging with compensation for asymmetric magnetization transfer effects SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cerebral blood flow; cat brain; magnetization transfer; adiabatic rapid passage ID POSITRON EMISSION TOMOGRAPHY; RELAXATION; WATER; TISSUE; O-15 AB The effects of off-resonance radio-frequency irradiation on the intensity of the MR signal from water protons in the cat brain are asymmetric around the chemical shift of the water signal, This asymmetry, which could arise from a shift in the magnetization transfer spectrum similar to 1.5 ppm upfield from the solvent water signal, must be taken into account to compensate for magnetization transfer effects inherent in arterial spin tagging approaches that use a single radio-frequency coil, Two approaches that either correct for, or circumvent, the apparent upfield shift of the magnetization transfer spectrum are presented, and a perfusion image of the cat brain, using flow-induced adiabatic inversion of arterial water protons, is presented. Other problems in obtaining quantitative cerebral blood flow values using the arterial spin tagging approach are discussed. C1 NIH,NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. NIH,OIR,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. NIH,NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. UNIV PENN,DEPT RADIOL,PHILADELPHIA,PA 19104. OI Jezzard, Peter/0000-0001-7912-2251 NR 23 TC 110 Z9 110 U1 1 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JAN PY 1996 VL 35 IS 1 BP 70 EP 79 DI 10.1002/mrm.1910350110 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TN368 UT WOS:A1996TN36800009 PM 8771024 ER PT J AU Ceci, JD AF Ceci, JD TI Mouse Chromosome 8 SO MAMMALIAN GENOME LA English DT Article RP Ceci, JD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PY 1996 VL 6 SI SI BP S151 EP S169 PG 19 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UX771 UT WOS:A1996UX77100008 PM 8800762 ER PT J AU Huppi, K Siwarski, D Eppig, JT Mock, BA AF Huppi, K Siwarski, D Eppig, JT Mock, BA TI Mouse Chromosome 15 SO MAMMALIAN GENOME LA English DT Article C1 JACKSON LAB,BAR HARBOR,ME 04609. RP Huppi, K (reprint author), NCI,GENET LAB,NIH,BLDG 37,RM 2B-21,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PY 1996 VL 6 SI SI BP S256 EP S270 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UX771 UT WOS:A1996UX77100015 PM 8800770 ER PT J AU Kozak, CA Bucan, M Goffinet, A Stephenson, DA AF Kozak, CA Bucan, M Goffinet, A Stephenson, DA TI Mouse Chromosome 5 SO MAMMALIAN GENOME LA English DT Article C1 UNIV PENN, DEPT PSYCHIAT, PHILADELPHIA, PA 19104 USA. FUNDP, SCH MED, DEPT PHYSIOL, NAMUR, BELGIUM. UCL, DEPT GENET & BIOMETRY, LONDON NX1 2HE, ENGLAND. RP Kozak, CA (reprint author), NIAID, MOLEC MICROBIOL LAB, BETHESDA, MD 20892 USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PY 1996 VL 6 SI SI BP S97 EP S112 PG 16 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UX771 UT WOS:A1996UX77100005 PM 8800781 ER PT J AU Mock, BA Stoye, J Spence, J Jackson, I Eppig, JT Fiedorek, FT Neumann, PE AF Mock, BA Stoye, J Spence, J Jackson, I Eppig, JT Fiedorek, FT Neumann, PE TI Mouse Chromosome 4 SO MAMMALIAN GENOME LA English DT Article C1 NATL INST MED RES,LONDON NW7 1AA,ENGLAND. WESTERN GEN HOSP,MRC,HUMAN GENET UNIT,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND. JACKSON LAB,BAR HARBOR,ME 04609. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. DALHOUSIE UNIV,DEPT ANAT & NEUROBIOL,HALIFAX,NS B3H 4H7,CANADA. RP Mock, BA (reprint author), NCI,GENET LAB,NIH,BLDG 37,RM 2B08,37 CONVENT DR MSC4255,BETHESDA,MD 20892, USA. NR 0 TC 12 Z9 12 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PY 1996 VL 6 SI SI BP S73 EP S96 PG 24 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UX771 UT WOS:A1996UX77100004 PM 8800780 ER PT B AU Sastry, S Vanmeter, JW Carson, RE AF Sastry, S Vanmeter, JW Carson, RE BE Hanson, KM Silver, RN TI Multimodality Bayesian algorithm for image reconstruction in positron emission tomography SO MAXIMUM ENTROPY AND BAYESIAN METHODS SE FUNDAMENTAL THEORIES OF PHYSICS LA English DT Proceedings Paper CT 15th International Workshop on Maximum Entropy and Bayesian Methods CY JUL 31-AUG 04, 1995 CL ST JOHNS COLL, SANTA FE, NM SP Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos Natl Lab, Radiog Diagnost Program, Santa Fe Inst HO ST JOHNS COLL DE Positron Emission Tomography; Magnetic Resonance images; Multimodality Image Reconstruction; Expectation Maximization; image segmentation AB Bayesian reconstruction algorithms offer a method for improving the image quality for Positron Emission Tomography. We present a new method which follows the overall strategy of Bayesian image reconstruction with priors, but without assumptions of global or piecewise smoothness, which are not satisfied in practice. Specifically, we use segmented Magnetic Resonance (MR) images to assign tissue composition to each reconstruction pixel. The reconstruction is performed as a constrained expection-maximization of activities of each tissue type, applying a prior based on the MR segmentations. The algorithm is tested in realistic simulations employing a full physical scanner model. RP Sastry, S (reprint author), NIH,PHYS SCI LAB,DIV COMP RES & TECH,BLDG 12A,ROOM 2007,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-4311-5 J9 FUND THEOR PY 1996 VL 79 BP 437 EP 441 PG 5 WC Multidisciplinary Sciences; Physics, Multidisciplinary; Physics, Mathematical; Statistics & Probability SC Science & Technology - Other Topics; Physics; Mathematics GA BH89J UT WOS:A1996BH89J00056 ER PT J AU Hellmich, HL Kos, L Cho, ES Mahon, KA Zimmer, A AF Hellmich, HL Kos, L Cho, ES Mahon, KA Zimmer, A TI Embryonic expression of glial cell-line derived neurotrophic factor (GDNF) suggests multiple developmental roles in neural differentiation and epithelial-mesenchymal interactions SO MECHANISMS OF DEVELOPMENT LA English DT Article DE gene expression; central nervous system; kidney development; intestine development; mesenchyme ID GROWTH-FACTOR-BETA; EARLY TOOTH DEVELOPMENT; DENTAL MESENCHYME; SYNDECAN; INDUCTION; KIDNEY; MORPHOGENESIS; ORGANOGENESIS; PROLIFERATION; TENASCIN AB We describe the cloning of the mouse glial cell line-derived neurotrophic factor (GDNF) gene and its expression during embryogenesis. GDNF is a distant member of the superfamily of TGF-beta related genes that was originally identified on the basis of its striking neurotrophic activity. GDNF is expressed in a highly dynamic pattern in the anterior neuroectoderm during early stages of neurogenesis between E7.5 and E10.5. Beginning at E10.5 GDNF is also expressed in several organs that develop through inductive epithelial-mesenchymal interactions. In those organs, GDNF expression is strictly confined to mesenchymal tissues and is not found in epithelia. Our results suggest multiple roles for GDNF during early stages of neuronal development and in epithelial-mesenchymal interactions. C1 NIMH,CELL BIOL LAB,DEV BIOL UNIT,BETHESDA,MD 20892. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RI Zimmer, Andreas/B-8357-2009 NR 42 TC 159 Z9 167 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JAN PY 1996 VL 54 IS 1 BP 95 EP 105 DI 10.1016/0925-4773(95)00464-5 PG 11 WC Developmental Biology SC Developmental Biology GA TT689 UT WOS:A1996TT68900009 PM 8808409 ER PT S AU Zheng, LX Fisher, G Combadiere, B Hornung, F Martin, D Pelfrey, C Wang, J Lenardo, M AF Zheng, LX Fisher, G Combadiere, B Hornung, F Martin, D Pelfrey, C Wang, J Lenardo, M BE Gupta, S Cohen, JJ TI Mature T lymphocyte apoptosis in the healthy and diseased immune system. SO MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VI: CELL CYCLE AND PROGRAMMED CELL DEATH IN THE IMMUNE SYSTEM SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Proceedings Paper CT 6th International Conference on Lymphocyte Activation and Immune Regulation - Cell Cycle and Programmed Cell Death in the Immune System CY FEB 02-04, 1996 CL NEWPORT BEACH, CA ID TUMOR-NECROSIS-FACTOR; FACTOR TNF RECEPTOR; CELL-DEATH; FAS-LIGAND; ACTIVATION; INDUCTION; CYTOTOXICITY; MICE; MECHANISMS; GENE RP Zheng, LX (reprint author), NIAID,IMMUNOL LAB,NATL INST HLTH,BLDG 10,BETHESDA,MD 20892, USA. RI Combadiere, Behazine/G-3881-2013; OI Pelfrey, Clara/0000-0002-6108-7555 NR 28 TC 6 Z9 6 U1 0 U2 1 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-2598 BN 0-306-45483-1 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1996 VL 406 BP 229 EP 239 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA BG55U UT WOS:A1996BG55U00024 PM 8910689 ER PT S AU Hallenbeck, JM AF Hallenbeck, JM BE Baethmann, A Kempski, O Plesnila, N Staub, F TI Significance of the inflammatory response in brain ischemia SO MECHANISMS OF SECONDARY BRAIN DAMAGE IN CEREBRAL ISCHEMIA AND TRAUMA SE ACTA NEUROCHIRURGICA SUPPLEMENTA LA English DT Proceedings Paper CT Vth International Symposium on Mechanisms of Secondary Brain Damage CY 1995 CL MAULS, ITALY DE leukocytes; inflammation; adhesion receptors; ischemia; stroke RP Hallenbeck, JM (reprint author), NINCDS,NIH,BLDG 36,RM 4A03,36 CONVENT DR MSC 4128,BETHESDA,MD 20892, USA. NR 0 TC 66 Z9 66 U1 0 U2 1 PU SPRINGER-VERLAG PI VIENNA PA MOLKERBASTEI 5, POSTFACH 367, A-1011 VIENNA, AUSTRIA SN 0065-1419 BN 3-211-82817-6 J9 ACT NEUR S JI Acta Neurochir. Suppl. PY 1996 VL 66 BP 27 EP 31 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BF81B UT WOS:A1996BF81B00005 PM 8780793 ER PT J AU DeBenedetti, V Bennett, WP Greenblatt, MS Harris, CC AF DeBenedetti, V Bennett, WP Greenblatt, MS Harris, CC TI p53 tumor suppressor gene: Implications for iatrogenic cancer and cancer therapy SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on the Long-Term Complications of Treatment of Children and Adolescents with Cancer CY JUN 10-11, 1994 CL NIAGARA FALLS, NY SP Glaxo Inc, Bristol Myers, Oncol Div, Assoc Res Childhood Canc Inc, Amer Canc Soc, New York State Div, Roswell Park Canc Inst ID HEPATITIS-B VIRUS; WILD-TYPE P53; CELL LUNG-CANCER; INDUCED POINT MUTATIONS; ORAL-CONTRACEPTIVE USE; NON-HODGKINS LYMPHOMA; HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; IONIZING-RADIATION; LIVER-CANCER C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 128 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PY 1996 SU 1 BP 2 EP 11 PG 10 WC Oncology; Pediatrics SC Oncology; Pediatrics GA UL890 UT WOS:A1996UL89000002 ER PT J AU Boice, JD AF Boice, JD TI Cancer following irradiation in childhood and adolescence SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on the Long-Term Complications of Treatment of Children and Adolescents with Cancer CY JUN 10-11, 1994 CL NIAGARA FALLS, NY SP Glaxo Inc, Bristol Myers, Oncol Div, Assoc Res Childhood Canc Inc, Amer Canc Soc, New York State Div, Roswell Park Canc Inst ID A-BOMB SURVIVORS; THYROID-CANCER; BREAST-CANCER; TUBERCULOSIS PATIENTS; ALKYLATING-AGENTS; X-RAYS; RADIATION; MORTALITY; LEUKEMIA; INFANCY RP Boice, JD (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,NIH,EXECUT PLAZA N,RM 408,BETHESDA,MD 20892, USA. NR 42 TC 1 Z9 1 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PY 1996 SU 1 BP 29 EP 34 PG 6 WC Oncology; Pediatrics SC Oncology; Pediatrics GA UL890 UT WOS:A1996UL89000006 ER PT J AU Newman, AH Shah, JH Izenwasser, S Heller, B Mattson, M Tortella, FC AF Newman, AH Shah, JH Izenwasser, S Heller, B Mattson, M Tortella, FC TI Highly selective sigma(1) ligands based on dextromethorphan SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article ID METHYL-D-ASPARTATE; RECEPTOR; PHARMACOPHORE; DEXTRORPHAN; ANALOGS; AGENTS AB A series of 17-substituted-3-hydroxy- or 3-alkoxy- analogs of dextromethorphan [(+)-3-methoxy-17-methylmorphinan] was prepared and evaluated for their binding affinities at sigma(1), sigma(2), and PCP sites on the NMDA receptor channel, in rat brain. The most potent and sigma(1)-selective compound was 3-ethoxy-17-benzylmorphinan (3e; K-i = 8.0 nM) that was >130 fold selective over sigma(2) sites and >5000-fold less potent at PCP sites. All of the compounds demonstrated low affinity at sigma(2) sites (K-i range of similar to 0.5 --> 10 mu M) and at PCP sites (K-i range of similar to 0.5 - 98 mu M). These compounds may provide useful tools for elucidation of the functional role of sigma(1) receptors in the central nervous system. C1 NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT NEUROPHARMCOL & MOL BIOL,WASHINGTON,DC 20307. RP Newman, AH (reprint author), NIDA,PSYCHOBIOL SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224, USA. RI Izenwasser, Sari/G-9193-2012 NR 31 TC 13 Z9 13 U1 0 U2 0 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PY 1996 VL 6 IS 2 BP 102 EP 117 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UP312 UT WOS:A1996UP31200003 ER PT J AU Nie, JY Shi, D Daly, JW Kirk, KL AF Nie, JY Shi, D Daly, JW Kirk, KL TI Synthesis of fluorodopamines: Effect of aryl fluoro substituents on affinities for adrenergic and dopaminergic receptors SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article ID RAT-BRAIN; BINDING; SITES; AGONIST; SYSTEM; D1 AB Monofluorine-substituted dopamines (1b-d) have been prepared previously. Synthetic routes to di- and trifluorinated dopamines (1e-h) were based on side chain elaboration of precursor fluorinated veratraldehydes. Binding data indicate that a 6-fluoro substituent decreases affinity at D-1-, D-2-, D-3- and D-4-dopamine receptors with the reduction (14-fold) being greatest at the D-2-dopamine receptor. A 2-fluoro or 5-fluoro substituent had little or no effect. Additional 2- and/or 5-fluoro substituents further reduced affinity of 6-fluorodopamine for dopamine receptors. At adrenergic receptors, mono-fluoro substituents had only modest (2-fold or less) effects on affinity, while 2,6-di-, and 5,6-difluoro substitution modestly decreased affinity. 2,5,6-Trifluorodopamine had very low affinity. RP Nie, JY (reprint author), NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PY 1996 VL 6 IS 5 BP 318 EP 332 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VF006 UT WOS:A1996VF00600003 ER PT J AU Kayakiri, H Jacobson, AE Rice, KC Rothman, RB Xu, H FlippenAnderson, JL George, C Aceto, MD Bowman, ER Harris, LS May, EL Partilla, JS Becketts, K AF Kayakiri, H Jacobson, AE Rice, KC Rothman, RB Xu, H FlippenAnderson, JL George, C Aceto, MD Bowman, ER Harris, LS May, EL Partilla, JS Becketts, K TI Probes for narcotic receptor mediated phenomena .24. Synthesis, single crystal X-ray analyses, in vitro and in vivo properties of 6 alpha- and 6 beta-iodo-3,14-dihydroxy-17-methyl-4,5 alpha-epoxymorphinans SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article ID OPIOID-MU-RECEPTORS; LIGAND-SELECTIVITY; RHESUS-MONKEYS; CLONED HUMAN; IOXY-AGO; TOMOGRAPHY; OPIATE AB The 6 alpha- and 6 beta-iodo-3,14-dihydroxy-17-methyl-4,5 alpha-epoxymorphinans, potential SPECT ligands, were synthesized and found to be mu-selective opioids, more potent in vitro and in vivo than their 6-hydroxy relatives. Single-crystal analysis showed that the 6 alpha- and 6 beta-iodine atoms are spatially closely located although the C-ring conformations of these compounds are quite different (twist-boat form vs. chair). These epimeric conformational differences were not reflected in their binding affinities. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL,RICHMOND,VA 23298. USN,RES LAB,WASHINGTON,DC 20375. NIDA,CLIN PSYCHOPHARMACOL SECT,ADDICT RES CTR,BALTIMORE,MD 21224. RP Kayakiri, H (reprint author), NIDDKD,MED CHEM LAB,NIH,BLDG 8,ROOM B1-22,8 CTR DR MSC 0815,BETHESDA,MD 20892, USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PY 1996 VL 6 IS 6 BP 427 EP 438 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VM091 UT WOS:A1996VM09100008 ER PT S AU Hearing, VJ AF Hearing, VJ BE Hori, Y Hearing, VJ Nakayama, J TI Melanogenic proteins as specific melanoma antigens SO MELANOGENESIS AND MALIGNANT MELANOMA: BIOCHEMISTRY, CELL BIOLOGY, MOLECULAR BIOLOGY, PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENT SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT International Symposium on Melanogenesis and Malignant Melanoma CY DEC 04-06, 1995 CL FUKUOKA, JAPAN SP Minist Educ Sci & Culture, Japan DE CTL; gp100; MARTI; TRP; tyrosinase C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82209-7 J9 INT CONGR SER PY 1996 VL 1096 BP 135 EP 148 PG 14 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA BG27L UT WOS:A1996BG27L00015 ER PT J AU Nemukhin, AV Solovev, VN Sergeev, GB Topol, IA AF Nemukhin, AV Solovev, VN Sergeev, GB Topol, IA TI Structure and spectra of methylmagnesium Grignard complexes SO MENDELEEV COMMUNICATIONS LA English DT Article ID ATOM; ABINITIO; CLUSTER; BOND AB The results of ab initio quantum chemistry calculations at the HF/6-31G* and MP2/6-31G* levels for the structure and vibrational spectra of the CH(3)MgX and CH(3)MgMgX (X = F, Cl, Br) Grignard reagents are presented. C1 NCI,FREDERICK CANC RES & DEV CTR,STRUCT BIOCHEM PROGRAM,FREDERICK BIOMED SUPERCOMP CTR,SAIC,FREDERICK,MD 21702. RP Nemukhin, AV (reprint author), MOSCOW MV LOMONOSOV STATE UNIV,DEPT CHEM,MOSCOW 119899,RUSSIA. RI Sergeev, Gleb/C-2644-2015; Nemukhin, Alexander/P-9662-2015 NR 14 TC 9 Z9 9 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0959-9436 J9 MENDELEEV COMMUN JI Mendeleev Commun. PD JAN PY 1996 IS 1 BP 5 EP 7 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA UJ324 UT WOS:A1996UJ32400003 ER PT B AU Porter, DW Nelson, VC Fivash, MJ Kasprzak, KS AF Porter, DW Nelson, VC Fivash, MJ Kasprzak, KS BE Collery, P Corbella, J Domingo, JL Etienne, JC Llobet, JM TI Mechanistic studies on the inhibition by Ni(II) of 8-oxo-2'-deoxyguanosine-5'-triphosphatase (MutT), a nucleotide pool-sanitizing enzyme SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 4 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 4th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 1996 CL BARCELONA, SPAIN SP Natl Ctr Toxicol Res, Food & Drug Adm, NCI, Assoc Reg Enseignement & Rech Sci Champagne Ardenne, Int Res Inst Metal Ions, Univ Rovira Virgili, Univ Barcelona, Escola Profess Med Treball, Direcc Gen Investigac Cient & Tecn, Commiss Univ Rec CIRIT Generalitat Catalunya RP Porter, DW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE BN 2-7420-0130-1 J9 MET ION BIO PY 1996 VL 4 BP 60 EP 62 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BH13A UT WOS:A1996BH13A00019 ER PT B AU McKenna, IM Waalkes, MP AF McKenna, IM Waalkes, MP BE Collery, P Corbella, J Domingo, JL Etienne, JC Llobet, JM TI Effects of zinc on metallothionein gene expression and cadmium accumulation in the testes and liver of rats SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 4 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 4th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 1996 CL BARCELONA, SPAIN SP Natl Ctr Toxicol Res, Food & Drug Adm, NCI, Assoc Reg Enseignement & Rech Sci Champagne Ardenne, Int Res Inst Metal Ions, Univ Rovira Virgili, Univ Barcelona, Escola Profess Med Treball, Direcc Gen Investigac Cient & Tecn, Commiss Univ Rec CIRIT Generalitat Catalunya RP McKenna, IM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE BN 2-7420-0130-1 J9 MET ION BIO PY 1996 VL 4 BP 63 EP 66 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BH13A UT WOS:A1996BH13A00020 ER PT B AU McKenna, IM Gordon, T Chen, LC Waalkes, MP AF McKenna, IM Gordon, T Chen, LC Waalkes, MP BE Collery, P Corbella, J Domingo, JL Etienne, JC Llobet, JM TI Pulmonary responses of Wistar rats and C57 and DBA mice to inhaled cadmium oxide SO METAL IONS IN BIOLOGY AND MEDICINE, VOL 4 SE METAL IONS IN BIOLOGY AND MEDICINE LA English DT Proceedings Paper CT 4th International Symposium on Metal Ions in Biology and Medicine CY MAY 19-22, 1996 CL BARCELONA, SPAIN SP Natl Ctr Toxicol Res, Food & Drug Adm, NCI, Assoc Reg Enseignement & Rech Sci Champagne Ardenne, Int Res Inst Metal Ions, Univ Rovira Virgili, Univ Barcelona, Escola Profess Med Treball, Direcc Gen Investigac Cient & Tecn, Commiss Univ Rec CIRIT Generalitat Catalunya RP McKenna, IM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN LIBBEY EUROTEXT PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE BN 2-7420-0130-1 J9 MET ION BIO PY 1996 VL 4 BP 465 EP 468 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BH13A UT WOS:A1996BH13A00132 ER PT S AU Abashkin, YG Burt, SK Collins, JR Cachau, RE Russo, N Erickson, JW AF Abashkin, YG Burt, SK Collins, JR Cachau, RE Russo, N Erickson, JW BE Russo, N Salahub, DR TI Density functional modeling of ligand-metal interactions and enzymatic activities in metalloenzymes. Peptide bond cleavage by carboxypeptidase A SO METAL-LIGAND INTERACTIONS: STRUCTURE AND REACTIVITY SE NATO ADVANCED SCIENCE INSTITUTES SERIES, SERIES C, MATHEMATICAL AND PHYSICAL SCIENCES LA English DT Proceedings Paper CT NATO Advanced Study Institute on Metal-Ligand Interactions - Structure and Reactivity CY SEP 04-16, 1994 CL CETRARO, ITALY SP NATO, CNR C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. NR 0 TC 13 Z9 13 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0258-2023 BN 0-7923-3833-2 J9 NATO ADV SCI INST SE PY 1996 VL 474 BP 1 EP 22 PG 22 WC Chemistry, Inorganic & Nuclear; Chemistry, Physical SC Chemistry GA BE86U UT WOS:A1996BE86U00001 ER PT S AU Ebnet, K Simon, MM Shaw, S AF Ebnet, K Simon, MM Shaw, S BE Ades, EW Morse, SA Rest, RF TI Regulation of chemokine gene expression in human endothelial cells by proinflammatory cytokines and Borrelia burgdorferi SO MICROBIAL PATHOGENESIS AND IMMUNE RESPONSE II SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Microbial Pathogenesis and Immune Response II CY OCT 25-28, 1995 CL NEW YORK, NY SP New York Acad Sci, AMGEN Inc, Ctr Dis Control & Prevent, Bristol Myers Squibb Pharm Res Inst, Merck Res Labs, Pfizer Inc, SmithKline Beecham Pharm ID ADHESION MOLECULES; SYNERGISTIC INDUCTION; RANTES CHEMOKINE; LYME ARTHRITIS; IFN-GAMMA; TNF-ALPHA; INTERLEUKIN-8; SECRETION; MONOCYTES; RECOGNITION C1 NCI, EXPT IMMUNOL BRANCH, NIH, BETHESDA, MD 20892 USA. RI Ebnet, Klaus/C-8314-2009 NR 32 TC 36 Z9 36 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 1-57331-017-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 797 BP 107 EP 117 DI 10.1111/j.1749-6632.1996.tb52953.x PG 11 WC Immunology; Microbiology; Multidisciplinary Sciences; Music SC Immunology; Microbiology; Science & Technology - Other Topics; Music GA BH28T UT WOS:A1996BH28T00011 PM 8993355 ER PT S AU Wynn, TA AF Wynn, TA BE Ades, EW Morse, SA Rest, RF TI Development of an antipathology vaccine for schistosomiasis SO MICROBIAL PATHOGENESIS AND IMMUNE RESPONSE II SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Microbial Pathogenesis and Immune Response II CY OCT 25-28, 1995 CL NEW YORK, NY SP New York Acad Sci, AMGEN Inc, Ctr Dis Control & Prevent, Bristol Myers Squibb Pharm Res Inst, Merck Res Labs, Pfizer Inc, SmithKline Beecham Pharm ID GAMMA IFN-GAMMA; GRANULOMA-FORMATION; TH2 CYTOKINES; MANSONI EGG; CELL CLONES; INTERLEUKIN-12; IL-12; INFLAMMATION; MICE; EXPRESSION RP Wynn, TA (reprint author), NIH, IMMUNOBIOL SECT, PARASIT DIS LAB, BLDG 4-126, BETHESDA, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 27 TC 12 Z9 13 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 1-57331-017-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 797 BP 191 EP 195 DI 10.1111/j.1749-6632.1996.tb52960.x PG 5 WC Immunology; Microbiology; Multidisciplinary Sciences; Music SC Immunology; Microbiology; Science & Technology - Other Topics; Music GA BH28T UT WOS:A1996BH28T00018 PM 8993362 ER PT J AU Wendler, D AF Wendler, D TI Deception in medical and behavioral research: Is it ever acceptable? SO MILBANK QUARTERLY LA English DT Article ID INFORMED CONSENT; ESCAPE AB Ethicists argue that deception is unacceptable, whereas researchers regard it as a necessary part of (certain kinds of) research. This impasse could be resolved by establishing the specific conditions under which deception in medical and behavioral research can be tolerated. An approach based on a consideration of the ''Ethical Principles of Psychologists and Code of Conduct,'' one of the few writings on this topic, would satisfy the needs of both parties. It takes the form of a requirement that subjects be informed of the use of deception before enrolling in a deceptive study. This ''second order consent'' approach to acceptable deception represents our best chance for reconciling respect for subjects with the occasional scientific need for deceptive research. RP Wendler, D (reprint author), NCI,BIOETH PROGRAM,BLDG 10,ROOM 1C 116,BETHESDA,MD 20892, USA. NR 18 TC 20 Z9 20 U1 0 U2 5 PU BLACKWELL PUBLISHERS PI CAMBRIDGE PA 350 MAIN STREET, STE 6, CAMBRIDGE, MA 02148-5023 SN 0887-378X J9 MILBANK Q JI Milbank Q. PY 1996 VL 74 IS 1 BP 87 EP & DI 10.2307/3350434 PG 29 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA UB321 UT WOS:A1996UB32100007 PM 8596525 ER PT J AU VanGent, DC McBlane, JF Ramsden, DA Sadofsky, MJ Hesse, JE Gellert, M AF VanGent, DC McBlane, JF Ramsden, DA Sadofsky, MJ Hesse, JE Gellert, M TI Initiation of V(D)J recombination in a cell-free system by RAG1 and RAG2 proteins SO MOLECULAR ANALYSIS OF DNA REARRANGEMENTS IN THE IMMUNE SYSTEM SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID BROKEN DNA-MOLECULES; MOUSE THYMOCYTES; REARRANGEMENT; INTERACTS; SIGNALS; BREAKS; CYCLE; GENE; ENDS RP VanGent, DC (reprint author), NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 22 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 217 BP 1 EP 10 PG 10 WC Immunology; Microbiology SC Immunology; Microbiology GA BJ66K UT WOS:A1996BJ66K00001 PM 8787614 ER PT J AU Ye, JP Zhang, XY Dong, ZG AF Ye, JP Zhang, XY Dong, ZG TI Characterization of the human granulocyte-macrophage colony-stimulating factor gene promoter: An AP1 complex and an Sp1-related complex transactivate the promoter activity that is suppressed by a YY1 complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ADENOVIRUS E1A PROTEIN; SERUM RESPONSE FACTOR; BOX-BINDING-PROTEINS; REGULATORY ELEMENTS; T-CELLS; C-FOS; SP1; TRANSCRIPTION; EXPRESSION; ACTIVATION AB It is well documented that a repeated CATT element in the human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoter is required for promoter activity. However, the transcription factors that are able to transactivate this enhancer element remain unidentified, Recently, we have found that nuclear factor YY1 can interact with the enhancer element. Here, we report that in addition to YY1, two other nuclear factors have been identified in the DNA-protein complexes formed by the CATT oligonucleotide and the Jurkat T-cell nuclear protein. One of these factors is AP1, and the other one is an Sp1-related protein. Results from transient transfection of Jurkat T cells have revealed that formation of both AP1 and the Sp1-related complex is required for the full enhancer activity of the CATT element. This result is supported by cotransfection of a c-jun expression vector and mutational analysis of the AP1 site or the Spl-related protein binding site. In contrast, formation of the WI complex suppresses enhancer activity, since deletion of the YY1 complex induces an augmentation of the enhancer activity and overexpression of WI results in an attenuation of the enhancer activity. Results from the mechanism study have revealed that YY1 is able to inhibit transactivation mediated by either AP1 or the Sp1-related protein, and YY1 suppressive activity is DNA binding dependent. Taken together, these data support the ideas that AP1 and the Sp1-related nuclear protein are required for transactivation of the human GM-CSF gene promoter and that YY1 can suppress transactivation of the promoter even under inducible conditions. C1 UNIV MINNESOTA,HORMEL INST,AUSTIN,MN 55912. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NR 46 TC 70 Z9 70 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1996 VL 16 IS 1 BP 157 EP 167 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TL345 UT WOS:A1996TL34500018 PM 8524292 ER PT J AU Preston, GA Lyon, TT Yin, YX Lang, JE Solomon, G Annab, L Srinivasan, DG Alcorta, DA Barrett, JC AF Preston, GA Lyon, TT Yin, YX Lang, JE Solomon, G Annab, L Srinivasan, DG Alcorta, DA Barrett, JC TI Induction of apoptosis by c-Fos protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING ACTIVITY; WILD-TYPE P53; HAMSTER EMBRYO CELLS; IMMEDIATE-EARLY GENE; V-FOS; CELLULAR-TRANSFORMATION; REDOX REGULATION; RAPID INDUCTION; TRANSGENIC MICE; CARCINOMA-CELLS AB The role of c-Fos in apoptosis was examined in two Syrian hamster embryo cell lines (sup(+)I and sup(-)II) and a human colorectal carcinoma cell line (RKO), using the chimeric Fos-estrogen receptor fusion protein c-FosER. As previously reported, contrasting responses were observed when these two cell lines were placed under growth factor deprivation conditions; sup(+)I cells were highly susceptible to apoptosis, whereas sup(-)II cells were resistant. In this report, we show that the activated c-FosER protein induces apoptosis in sup(-)II preneoplastic cells in serum-free medium, indicating that c-Fos protein can induce apoptotic cell death in these cells. c-Fos-induced apoptosis was not blocked by the protein synthesis inhibitor cycloheximide, suggesting that the c-Fos transcriptional activation activity is not involved. This conclusion was further supported by the observation that overexpression of v-Fos, which is highly proficient in transcriptional activation but deficient in the transcriptional repression activity associated with c-Fos, did not induce apoptosis. Constitutively expressed Bcl-2 delayed the onset of low-serum-induced apoptosis in sup(+)I cells and enhanced survival in sup(-)II cells. Further, coexpression of Bcl-2 and c-FosER in sup(+)I or sup(-)II cells protected the cells from c-FosER-induced apoptosis. The possibility that c-FosER-induced apoptosis requires a p53 function was examined. Colorectal carcinoma RKO(p53+/+) cells, which do not normally undergo apoptosis in serum-free medium, showed apoptotic DNA fragmentation upon expression and activation of c-FosER. Further, when the wild-type p53 protein was diminished in the RKO cells by infection with the papillomavirus E6 gene, subsequent c-FosER-induced apoptosis was blocked. The data suggest that c-Fos protein plays a causal role in the activation of apoptosis in a p53-dependent manner. This activity does not require new protein synthesis and is blocked by overexpression of Bcl-2 protein. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 83 TC 175 Z9 176 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1996 VL 16 IS 1 BP 211 EP 218 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TL345 UT WOS:A1996TL34500023 PM 8524298 ER PT J AU Atwood, A Lin, JH Levin, HL AF Atwood, A Lin, JH Levin, HL TI The retrotransposon Tf1 assembles virus-like particles that contain excess Gag relative to integrase because of a regulated degradation process SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; STRANDED-RNA VIRUS; POL FUSION PROTEIN; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; ELEMENT TRANSPOSITION; REVERSE-TRANSCRIPTASE; TY1 TRANSPOSITION; EXPRESSION AB The retrotransposon Tf1, isolated from Schizosaccharomyces pombe, contains a single open reading frame with sequences encoding Gag, protease, reverse transcriptase, and integrase (IN), Tf1 has previously been shown to possess significant transposition activity. Although Tf1 proteins do assemble into virus like particles, the assembly does not require readthrough of a translational reading frame shift or stop codon, common mechanisms used by retroelements to express Gag in molar excess of the polymerase proteins, This study was designed to determine if Tf1 particles contain equal amounts of Gag and polymerase proteins or whether they contain the typical molar excess of Gag, lifter using two separate methods to calibrate the strength of our antibodies, we found that both S. pombe extracts and partially purified Tf1 particles contained a 26-fold molar excess of Gag relative to IN. Knowing that Gag and IN are derived from the same Tf1 primary translation product, we concluded that the excess Gag most likely resulted from specific degradation of IN, We obtained evidence of regulated IN degradation in comparisons of Tf1 protein extracted from lag-phase cells and that extracted from stationary-phase cells. The log-phase cells contained equal molar amounts of Gag and IN, whereas cells approaching stationary phase rapidly degraded IN, leaving an excess of Gag, Analysis of the reverse transcripts indicated that the bulk of reverse transcription occurred within the particles that possess a molar excess of Gag. C1 NICHHD, MOLEC GENET LAB, BETHESDA, MD 20892 USA. NR 39 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1996 VL 16 IS 1 BP 338 EP 346 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TL345 UT WOS:A1996TL34500037 PM 8524313 ER PT J AU Gorospe, M Martindale, JL Sheikh, MS Fornace, AJ Holbrook, NJ AF Gorospe, M Martindale, JL Sheikh, MS Fornace, AJ Holbrook, NJ TI Regulation of p21(CIP1/WAF1) expression by cellular stress: p53-dependent and p53-independent mechanisms SO MOLECULAR AND CELLULAR DIFFERENTIATION LA English DT Article DE genotoxic stress; signal transduction; mRNA stability; protein stability; p53 ID P53; PROTEIN; INHIBITOR; KINASES; ARREST; CELLS; P21 AB p21(CIP1/WAF1) (also referred to as SDI1, CIP1, WAF1, CAP20, and MDA6) was independently identified in several different laboratories based on its enhanced expression in senescent cells (SDI1) [1], its inhibitory effect on cyclin-dependent kinase (cdk) activity (CIP1) [2], its p53-mediated induction (WAF1) [3], and its elevated expression during differentiation (MDA6) [4]. p21(CIP1/WAF1) was also isolated in the original hamster library from which the growth arrest and DNA damage-inducible genes GADD45 and GADD153 were cloned; at least 5 independent isolates were subsequently found to encode the hamster gene, including DDIA13 and DDIA20 [5]. Given its growth inhibitory properties and its regulation by p53, it has received broad attention as a critical mediator of p53 tumor suppressive functions, most notably the G1 growth arrest and/or apoptosis that occur with certain genotoxic stresses. However, a number of recent studies have demonstrated that p21(CIP/WAF1) is upregulated in response to a variety of stress signals in the absence of p53, indicating the existence of alternative mechanisms involved in regulating p21(CIP/WAF1) expression and suggesting a more generalized role for this protein during the cellular response to stress. In this review, we summarize our current knowledge concerning the mechanisms serving to regulate p21(CIP1/WAF1) gene expression in response to genotoxic and related growth-suppressive agents. We focus on the signal transduction pathways involved in the transcriptional activation of p21(CIP1/WAF1) the posttranscriptional control of p21(CIP1/WAF1) expression, and the requirement for p53 in these processes. Finally, we address the functional role of p21(CIP1/WAF1) in the cellular response to genotoxic stress. While we appreciate the fact that many of the agents discussed can lead to terminal differentiation in certain cell types, p21(CIP1/WAF1) expression during development and differentiation will not be emphasized here. C1 NIA,GERONTOL RES CTR,SECT GENE EXPRESS & AGING,NIH,BALTIMORE,MD 21224. NCI,MOLEC PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. NR 60 TC 25 Z9 25 U1 0 U2 2 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, BOCA RATON, FL 33431 SN 1065-3074 J9 MOL CELL DIFFER JI Mol. Cell. Differ. PY 1996 VL 4 IS 1 BP 47 EP 65 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UP326 UT WOS:A1996UP32600005 ER PT J AU Alesse, E Krutzsch, H Michelotti, G Levens, D AF Alesse, E Krutzsch, H Michelotti, G Levens, D TI A positive acting cis-element in intron I of c-myc mutated in Burkitt's lymphoma binds RFX1 SO MOLECULAR AND CELLULAR DIFFERENTIATION LA English DT Article DE c-myc; RFX; Burkitt lymphoma ID DNA-BINDING; 1ST INTRON; GENE; ACTIVATION; EXPRESSION; CELLS; TRANSCRIPTION; MUTATIONS; ENHANCER; PROTEIN AB The c-myc gene is required for the regulation of normal cell growth, differentiation, and apoptosis. Deregulated c-myc expression contributes to the pathogenesis of many neoplasms. Proper regulation of c-myc is lost in Burkitt's lymphoma, which inevitably suffers a chromosomal translocation between the c-myc locus on chromosome 8 and one of the immunoglobulin loci. In addition, mutations, deletions, and/or duplications are often detected in exon I and intron I of the translocated allele, clustered in discrete domains defining cis-elements or protein binding sites. A 20-bp segment of the intron I of the human c-myc gene has been identified previously as a binding site for a 138-kDa nuclear phosphoprotein termed myc intron factor (MIF). This binding site is mutated in about 80% of the Burkitt's lymphomas and the mutations abolish binding activity. In this article we describe the biochemical characterization of MIF protein and its identity with RFX1, a major transregulator of MHC class II genes. The existence of a 35-kDa polypeptide component of the MIF protein is also demonstrated. Because the intron I site recognized by MIF/RFX1 up-regulates a transfected myc promoter, a scheme linking the positive action and mutation of the MIF-RFX1 intron binding site with c-myc disregulation and the pathogenesis of Burkitt's lymphoma is discussed. C1 NATL CANC INST,PATHOL LAB,NATL INST HLTH,BETHESDA,MD 20892. RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 43 TC 1 Z9 1 U1 0 U2 1 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, BOCA RATON, FL 33431 SN 1065-3074 J9 MOL CELL DIFFER JI Mol. Cell. Differ. PY 1996 VL 4 IS 2 BP 127 EP 148 PG 22 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UU576 UT WOS:A1996UU57600001 ER PT J AU Freemerman, AJ Maloney, NJ Birrer, MJ Szabo, E Grant, S AF Freemerman, AJ Maloney, NJ Birrer, MJ Szabo, E Grant, S TI Bryostatin 1 potentiates 1-[beta-D-arabinofuranosyl]cytosine-mediated antiproliferative effects in c-jun dominant-negative human myeloid leukemia cells (U937/TAM67) through a nonapoptotic mechanism SO MOLECULAR AND CELLULAR DIFFERENTIATION LA English DT Article DE apoptosis; ara-C; bryostatin 1; c-jun; TAM67; U937 cells ID PROTEIN-KINASE-C; HL-60 CELLS; MACROPHAGE DIFFERENTIATION; MONOCYTIC DIFFERENTIATION; EXPRESSION; ACTIVATOR; APOPTOSIS; MUTANT; DEATH; TRANSFORMATION AB Recent studies suggest that exposure of leukemic cells to a differentiating stimulus following a DNA-damaging agent leads to potentiation of apoptosis or programmed cell death. The present studies were undertaken to evaluate the contribution of the transcription factor c-Jun to apoptosis and growth inhibition induced by the sequential administration of 1-beta-D-arabinofuranosylcytosine (ara-C) and the protein kinase C activator bryostatin 1 in human monocytic leukemia cells (U937). To address this issue, a U937 cell Line stably transfected with a dominant-negative, c-Jun transactivation domain-deficient mutant (TAM67), was employed. The mutant TAM67 protein interferes with normal c-Jun function and AP-1 activation through a ''quenching'' mechanism. TAM67-expressing cells and cells containing empty vector (pMM) were equally susceptible to apoptosis induced by exposure to ara-C (1 mu M; 6 h); moreover, this effect was not altered by subsequent exposure of cells to bryostatin 1 (10 nM; 24 h). However, clonogenic TAM67-expressing cells were less susceptible to the antiproliferative effects of ara-C and more susceptible to growth inhibition by bryostatin 1 than their empty vector counterparts. In addition, subsequent exposure to bryostatin 1 substantially increased growth inhibition by ara-C in TAM67-expressing cells despite failing to potentiate apoptosis. Whereas 10 nM bryostatin 1 was ineffective in triggering maturation of pMM cells, it partially induced differentiation in their TAM67-expressing counterparts, manifested by increased expression of the maturation marker CD11b, modest up-regulation of native c-Jun, and limited dephosphorylation of the retinoblastoma protein pRb. Sequential administration of ara-C followed by bryostatin 1 led to further up-regulation of native c-Jun, particularly in TAM67-expressing cells, but failed to induce pRb hypophosphorylation in either cell line. Collectively, these findings indicate that bryostatin 1 reverses, at least in part, the reduced susceptibility of clonogenic U937 cells to ara-C conferred by c-Jun dysregulation, and further suggest that this phenomenon proceeds via nonapoptotic mechanisms. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,DIV HEMATOL ONCOL,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL,RICHMOND,VA 23298. NCI,PREVENT RES BRANCH,ROCKVILLE,MD 20850. NR 41 TC 2 Z9 2 U1 0 U2 1 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, BOCA RATON, FL 33431 SN 1065-3074 J9 MOL CELL DIFFER JI Mol. Cell. Differ. PY 1996 VL 4 IS 3 BP 247 EP 262 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VL191 UT WOS:A1996VL19100003 ER PT J AU Nieroda, C Pestka, S Schlom, J Greiner, JW AF Nieroda, C Pestka, S Schlom, J Greiner, JW TI Interferon-omega augments major histocompatibility and human tumor-associated antigen expression SO MOLECULAR AND CELLULAR DIFFERENTIATION LA English DT Article DE interferon-omega; carcinoembryonic antigen; ICAM-1; HLA expression ID HUMAN-LEUKOCYTE INTERFERONS; MONOCLONAL-ANTIBODY CC49; HUMAN ALPHA-INTERFERON; CARCINOEMBRYONIC ANTIGEN; GAMMA-INTERFERON; ANTIPROLIFERATIVE ACTIVITY; COLON-CARCINOMA; MELANOMA-CELLS; I INTERFERONS; RECOMBINANT AB Human interferon-omega (IFN-omega) is a recently described interferon species with an amino acid sequence that is approximately 60% homologous with IFN-alpha 2a, like IFN-beta it is a single gene species that contains a site for N-glycosylation. The present study investigated the ability of IFN-omega omega to upregulate the level of expression of major histocompatibility (MHC) and non-MHC (i.e., tumor-associated antigens) on the surface of human colorectal and breast carcinoma cells. Flow cytometric data clearly showed that treatment of human colorectal (i.e., HT-29, WiDr) or breast (MCF-7) tumor cells with IFN-omega increased carcinoembryonic antigen (CEA) and episialin (DF3/MUC1) expression. IFN-omega treatment also increased HLA class I and ICAM-1 expression on the surface of those as well as other human colorectal (MIP) and breast (BT-20, ZR-75-1, T47D) tumor cells. Preincubation with anti-IFN-alpha, -beta, or -gamma-neutralizing antibodies failed to alter the antigen upregulation properties of IFN-omega. IFN-omega was unable to induce HLA class II expression. Therefore, the changes in CEA and HLA class I expression agreed with previous studies that IFN-omega functions as a type I interferon. Additional results revealed additive/synergistic increases of CEA, HLA class I, and ICAM-1 expression when low doses of IFN-omega and IFN-gamma were combined. IFN-omega exhibited lower antiproliferative activity compared with other type I (i.e., IFN-alpha 2a and IFN-beta) interferons. Additional studies should compare the in vivo ability of IFN-omega to upregulate MHC and non-MHC antigen expression in monoclonal antibody and/or vaccine-based approaches to tumor detection/therapy. C1 NCI,NIH,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MOL GENET & MICROBIOL,PISCATAWAY,NJ 08854. NR 52 TC 4 Z9 4 U1 0 U2 1 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 SN 1065-3074 J9 MOL CELL DIFFER JI Mol. Cell. Differ. PY 1996 VL 4 IS 4 BP 335 EP 351 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC134 UT WOS:A1996WC13400003 ER PT J AU Adachi, H Dawson, MI Jetten, AM AF Adachi, H Dawson, MI Jetten, AM TI Suppression by retinoids of the induction of the CCAAT/enhancer-binding protein alpha and the nuclear receptors PPAR gamma and ROR gamma during adipocyte differentiation of 3T3-L1 cells SO MOLECULAR AND CELLULAR DIFFERENTIATION LA English DT Article DE retinoids; enhancer-binding protein alpha; nuclear receptor PPAR gamma and ROR gamma; adipocyte differentiation; 3T3-L1 cells ID GENE-EXPRESSION; PEROXISOME PROLIFERATOR; ADIPOSE DIFFERENTIATION; MESSENGER-RNA; ACID; PREADIPOCYTES; BETA; ADIPOGENESIS; ENHANCER; IDENTIFICATION AB In this study, we analyze in 3T3-L1 preadipocytes the effects of retinoids on the expression of PPAR gamma and C/EBP alpha, two transcriptional factors that play a key regulatory role early in adipogenesis, and the nuclear orphan receptors ROR alpha and ROR gamma which are induced at a later stage of adipocyte differentiation. We demonstrate that the RAR-selective retinoid SRI-6751-84 inhibited the induction of PPAR gamma, C/EBP alpha, ROR alpha and gamma, as well as the adipocyte marker aP2, while the RXR-selective retinoid SR11217 had only a minimal effect. The RAR-selective retinoid was able to repress the expression of these mRNAs at nanomolar concentrations. The RAR alpha-selective antagonist Ro41-5253 was able to block the repression of PPAR gamma, C/EBP alpha, aP2, ROR alpha and -gamma expression by the RAR-selective retinoid. The retinoid SR11302, which exhibits anti-AP1 activity but no RARE- or RXRE-dependent transactivating activity, had no effect on the induction of these genes, suggesting that the inhibition of adipogenesis by retinoids is not related to their anti-API activity. In addition, the RAR alpha-selective retinoid Ro40-6055 but not the RAR gamma-selective retinoid CD437/SR11248 inhibited the induction of ROR gamma and PPAR gamma. The repression of PPAR gamma and C/EBP alpha expression suggest that retinoids inhibit adipogenesis at an early stage of differentiation. This response may at least in part be responsible for the inhibition of ROR and aP2 expression. In addition, our observations indicate that the repression of PPAR gamma, C/EBP alpha and RORs by retinoids is mediated through an RAR alpha-dependent signaling pathway. C1 NIEHS,NIH,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. SRI INT,BIOORGAN CHEM LAB,MENLO PK,CA 94025. OI Jetten, Anton/0000-0003-0954-4445 NR 44 TC 11 Z9 11 U1 0 U2 1 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 SN 1065-3074 J9 MOL CELL DIFFER JI Mol. Cell. Differ. PY 1996 VL 4 IS 4 BP 365 EP 381 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WC134 UT WOS:A1996WC13400005 ER PT J AU Fan, CM Kuwana, E Bulfone, A Fletcher, CF Copeland, NG Jenkins, NA Crews, S Martinez, S Puelles, L Rubenstein, JLR TessierLavigne, M AF Fan, CM Kuwana, E Bulfone, A Fletcher, CF Copeland, NG Jenkins, NA Crews, S Martinez, S Puelles, L Rubenstein, JLR TessierLavigne, M TI Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of down syndrome SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID SPATIALLY RESTRICTED EXPRESSION; CNS MIDLINE DEVELOPMENT; GENETIC-LINKAGE MAP; DIOXIN RECEPTOR; FLOOR PLATE; FOREBRAIN; PROTEIN; ORGANIZATION; CLONING; ENCODES AB The single-minded (sim) gene encodes a transcriptional regulator that functions as a key determinant of central nervous system (CNS) midline development in Drosophila, We report here the identification of two murine homologs of sim, Sim1 and Sim2 whose products show a high degree of sequence conservation with Drosophila SIM in their amino-terminal halves, with each containing a basic helix-loop-helix domain as well as a PAS domain, Sim1 maps to the proximal region of mouse chromosome 10, whereas Sim2 maps to a portion of the distal end of chromosome 16 that is syntenic to the Down syndrome critical region of human chromosome 21., Recent exon-trapping studies have identified in the critical region several exons of a human sim homolog which appears to be the homolog of murine Sim2; this has led to the hypothesis that increased dosage of this sim homolog in cases of trisomy 21 might be a causal factor in the pathogenesis of Down syndrome, We have examined the expression patterns of the Sim genes during embryogenesis. Both genes are expressed in dynamic and selective fashion in specific neuromeric compartments of the developing forebrain, and the expression pattern of Sima provides evidence for early regionalization of the diencephalon prior to any overt morphological differentiation in this region, Outside the CNS, Sim1 is expressed in mesodermal and endodermal tissues, including developing somites, mesonephric duct, and foregut, Sim2 is expressed in facial and trunk cartilage, as well as trunk muscles. Both murine Sim genes are also expressed in the developing kidney, Our data suggest that the Sim genes play roles in directing the regionalization of tissues where they are expressed, Moreover, the expression pattern documented for Sima may provide insights into its potential roles in Down syndrome. C1 UNIV CALIF SAN FRANCISCO,DEPT ANAT,CELL BIOL PROGRAM,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT ANAT,PROGRAM DEV BIOL,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT ANAT,PROGRAM NEUROSCI,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,CTR NEUROBIOL & PSYCHIAT,PROGRAM DEV BIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,CTR NEUROBIOL & PSYCHIAT,PROGRAM NEUROSCI,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,LANGLEY PORTER PSYCHIAT INST,SAN FRANCISCO,CA 94143. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599. UNIV MURCIA,FAC MED,DEPT MORPHOL SCI,E-30100 MURCIA,SPAIN. OI Martinez, Salvador/0000-0002-2910-8926; Martinez, Salvador/0000-0002-9320-4103 FU NIMH NIH HHS [K02 MH01046-01, R01 MH4942801, R01 MH51561-01A1]; Telethon [TGM06S01, TGM94000] NR 56 TC 157 Z9 159 U1 0 U2 9 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD JAN PY 1996 VL 7 IS 1 BP 1 EP 16 DI 10.1006/mcne.1996.0001 PG 16 WC Neurosciences SC Neurosciences & Neurology GA TX496 UT WOS:A1996TX49600001 PM 8812055 ER PT J AU Schiffmann, R AF Schiffmann, R TI Studies on patients with an unclassified leukodystrophy SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article; Proceedings Paper CT Scientific Symposium on the MRI Suggests a Leukodystrophy, but Test are Negative - What Should We Do CY MAY 07-09, 1994 CL KISHWAUKEE COMMUNITY HOSPITAL, DE KALB, IL SP United Leukodystrophy Fdn HO KISHWAUKEE COMMUNITY HOSPITAL RP Schiffmann, R (reprint author), NIND,DEV & METAB NEUROL BRANCH,NIH,BETHESDA,MD, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD JAN PY 1996 VL 27 IS 1 BP 46 EP 47 PG 2 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA TU533 UT WOS:A1996TU53300046 ER PT S AU Bellus, GA McIntosh, I Szabo, J Aylsworth, A Kaitila, I Francomano, CA AF Bellus, GA McIntosh, I Szabo, J Aylsworth, A Kaitila, I Francomano, CA BE deCrombrugghe, B Horton, WA Olsen, BR Ramirez, F TI Hypochondroplasia: Molecular analysis of the fibroblast growth factor receptor 3 gene SO MOLECULAR AND DEVELOPMENTAL BIOLOGY OF CARTILAGE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Molecular and Developmental Biology of Cartilage CY SEP 27-30, 1995 CL BETHESDA, MD SP New York Acad Sci ID ACHONDROPLASIA; MUTATIONS; FGFR3; DWARFISM; LINKAGE; DOMAIN; 4P C1 NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21287. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,BRAIN DEV RES CTR,CHAPEL HILL,NC 27599. HELSINKI UNIV HOSP,DEPT CLIN GENET,SF-00290 HELSINKI,FINLAND. NR 25 TC 18 Z9 18 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 1-57331-010-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 785 BP 182 EP 187 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Science & Technology - Other Topics GA BF92H UT WOS:A1996BF92H00021 PM 8702125 ER PT S AU Bernier, SM Yamada, Y AF Bernier, SM Yamada, Y BE deCrombrugghe, B Horton, WA Olsen, BR Ramirez, F TI Modulation of annexin V during chondrocytic differentiation in vitro SO MOLECULAR AND DEVELOPMENTAL BIOLOGY OF CARTILAGE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Molecular and Developmental Biology of Cartilage CY SEP 27-30, 1995 CL BETHESDA, MD SP New York Acad Sci ID MATRIX VESICLES; CELL-LINE; BINDING RP Bernier, SM (reprint author), NIDR,DEV BIOL LAB,30 CONVENT DR MSC 4370,BETHESDA,MD 20892, USA. NR 5 TC 2 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 1-57331-010-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 785 BP 212 EP 214 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Science & Technology - Other Topics GA BF92H UT WOS:A1996BF92H00028 PM 8702132 ER PT S AU FrancisWest, PH Richardson, MK Bell, E Chen, P Luyten, F Adelfattah, A Barlow, AJ Brickell, PM Wolpert, L Archer, CW AF FrancisWest, PH Richardson, MK Bell, E Chen, P Luyten, F Adelfattah, A Barlow, AJ Brickell, PM Wolpert, L Archer, CW BE deCrombrugghe, B Horton, WA Olsen, BR Ramirez, F TI The effect of overexpression of BMPs and GDF-5 on the development of chick limb skeletal elements SO MOLECULAR AND DEVELOPMENTAL BIOLOGY OF CARTILAGE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Molecular and Developmental Biology of Cartilage CY SEP 27-30, 1995 CL BETHESDA, MD SP New York Acad Sci ID TGF-BETA-SUPERFAMILY; MEMBER C1 ST GEORGE HOSP, SCH MED, DEPT ANAT, LONDON SW17 0RE, ENGLAND. UCL, DEPT ANAT & DEV BIOL, LONDON W1P 6DB, ENGLAND. NIDR, NIH, BONE RES BRANCH, BETHESDA, MD 20892 USA. UNIV WALES COLL CARDIFF, DEPT ANAT, CARDIFF CF1 3YF, S GLAM, WALES. RP FrancisWest, PH (reprint author), UNITED MED & DENT SCH, DEPT CRANIOFACIAL DEV, GUYS TOWER, FLOOR 28, LONDON SE1 9RT, ENGLAND. RI Bell, Esther/C-5329-2009; Richardson, Michael/E-8269-2011 NR 3 TC 14 Z9 15 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 1-57331-011-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 785 BP 254 EP 255 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Science & Technology - Other Topics GA BF92H UT WOS:A1996BF92H00040 PM 8702145 ER PT S AU Nakata, K Miyamoto, S Bernier, S Tanaka, M Utani, A Krebsbach, P Rhodes, C Yamada, Y AF Nakata, K Miyamoto, S Bernier, S Tanaka, M Utani, A Krebsbach, P Rhodes, C Yamada, Y BE deCrombrugghe, B Horton, WA Olsen, BR Ramirez, F TI The C-propeptide of type II procollagen binds to the enhancer region of the Type II procollagen gene and regulates its transcription SO MOLECULAR AND DEVELOPMENTAL BIOLOGY OF CARTILAGE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Molecular and Developmental Biology of Cartilage CY SEP 27-30, 1995 CL BETHESDA, MD SP New York Acad Sci RP Nakata, K (reprint author), NIDR,NIH,BETHESDA,MD 20892, USA. NR 2 TC 8 Z9 8 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 1-57331-010-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 785 BP 307 EP 308 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Science & Technology - Other Topics GA BF92H UT WOS:A1996BF92H00057 PM 8702163 ER PT S AU Keller, JR Ruscetti, FW Heidecker, G Linnekin, DM Rapp, U Troppmair, J Gooya, J Muszynski, KW AF Keller, JR Ruscetti, FW Heidecker, G Linnekin, DM Rapp, U Troppmair, J Gooya, J Muszynski, KW BE Wolff, L Perkins, AS TI The effect of c-raf antisense oligonucleotides on growth factor-induced proliferation of hematopoietic cells SO MOLECULAR ASPECTS OF MYELOID STEM CELL DEVELOPMENT SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Molecular Aspects of Myeloid Stem Cell Development CY APR 30-MAY 03, 1995 CL ANNAPOLIS, MD SP Natl Canc Inst, AMGEN Inc, Bristol Myers Squibb Pharm Inst, Merck, Sandoz Res Inst, Bayer Corp, Upjohn Co ID COLONY-STIMULATING FACTOR; SIGNAL TRANSDUCTION; KINASE-ACTIVITY; PROTEIN-KINASE; MAP KINASE; STEM-CELLS; PHOSPHORYLATION; ACTIVATION; PROTOONCOGENE; RECEPTORS AB While it is well established that Raf-l kinase is activated by phosphorylation in growth factor-dependent hematopoietic cell lines stimulated with a variety of hematopoietic growth factors, little is known about the biological effects of Raf-1 activation on normal hematopoietic cells. Therefore, we examined the requirement for Raf-l in growth factor-regulated proliferation and differentiation of hematopoietic cells using c-raf antisense oligonucleotide. Raf-l is required for the proliferation of growth factor dependent cell lines stimulated by IL-2, IL-3, G-CSF, GM-CSF and EPO that bind to the hematopoietin class of receptors. Raf-l is also required for the proliferation of cell lines stimulated by growth factors that use the tyrosine kinase containing receptor class, including SLF and CSF-1. In addition, Raf-l is also required for IL-6-, LIF- and OSM-induced proliferation whose receptors share the gp 130 subunit. In contrast to previous results which demonstrated that IL-4 could not activate Raf-l kinase, c-raf antisense oligonucleotides also inhibited IL-4-induced proliferation of T cell and myeloid cell lines. Using normal hematopoietic cells, c-raf antisense oligonucleotides completely suppressed the colony formation of murine hematopoietic progenitors in response to single growth factors, such as IL-3, CSF-1 or GM-CSF. Further, c-raf antisense oligonucleotides inhibited the growth of murine progenitors stimulated with synergistic combinations of growth factors (required for primitive progenitor growth) including two, three and four factor combinations. In comparison to murine hematopoietic cells, c-raf antisense oligonucleotides also inhibited both IL-3 and GM-CSF-induced colony formation of CD 34+ purified human progenitors. In addition, Raf-l is required for the synergistic response of CD 34+ human bone marrow progenitors to multiple cytokines; however, this effect was only observed when additional antisense oligonucleotides were added to the cultures at day 7 of a 14 day assay. Finally, Raf-l is required for the synergistic response of human Mo-7e cells and of normal human fetal liver cells to five factor combinations. Thus, Raf-l is required to transduce growth factor-induced proliferative signals in factor-dependent progenitor cell lines for all known classes of hematopoietic growth factor receptors, and is required for the growth of normal murine and human bone marrow-derived progenitors. C1 NCI,FREDERICK CANC RES & DEV PROGRAM,BRMP,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV PROGRAM,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Keller, JR (reprint author), NCI,FREDERICK CANC RES & DEV PROGRAM,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 25 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60414-6 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 211 BP 43 EP 53 PG 11 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BG27J UT WOS:A1996BG27J00005 PM 8585963 ER PT S AU Li, W Pierce, JH AF Li, W Pierce, JH BE Wolff, L Perkins, AS TI Protein kinase C-delta, an important signaling molecule in the platelet-derived growth factor beta receptor pathway SO MOLECULAR ASPECTS OF MYELOID STEM CELL DEVELOPMENT SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Molecular Aspects of Myeloid Stem Cell Development CY APR 30-MAY 03, 1995 CL ANNAPOLIS, MD SP Natl Canc Inst, AMGEN Inc, Bristol Myers Squibb Pharm Inst, Merck, Sandoz Res Inst, Bayer Corp, Upjohn Co ID CELLS; DIFFERENTIATION; ACTIVATION; EXPRESSION; PDGF; PHOSPHORYLATION; TRANSDUCTION; ALPHA RP Li, W (reprint author), NCI,CELLULAR & MOL BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 23 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60414-6 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 211 BP 55 EP 65 PG 11 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BG27J UT WOS:A1996BG27J00006 PM 8585964 ER PT S AU Wolff, L Koller, R Bies, J Nazarov, V Hoffman, B Amanullah, A Krall, M Mock, B AF Wolff, L Koller, R Bies, J Nazarov, V Hoffman, B Amanullah, A Krall, M Mock, B BE Wolff, L Perkins, AS TI Retroviral insertional mutagenesis in murine promonocytic leukemias: C-myb and Mm/1. SO MOLECULAR ASPECTS OF MYELOID STEM CELL DEVELOPMENT SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Molecular Aspects of Myeloid Stem Cell Development CY APR 30-MAY 03, 1995 CL ANNAPOLIS, MD SP Natl Canc Inst, AMGEN Inc, Bristol Myers Squibb Pharm Inst, Merck, Sandoz Res Inst, Bayer Corp, Upjohn Co ID V-MYB; TRANSCRIPTIONAL ACTIVATION; TERMINAL DIFFERENTIATION; MYELOID CELLS; BALB/C MICE; GENE; EXPRESSION; PROTEINS; TUMORS; SITES AB Studies have focused on two genetic loci, c-myb and MmlI, whose activation by retroviral insertional mutagenesis contribute to promonocytic leukemia in our acute monocytic leukemia (AMoL) model. Multiple mechanisms of activation of c-myb by retroviral insertional mutagenesis implicate both transcriptional deregulation and protein truncation in conversion of this proto-oncogene to an oncogene. Because transformation by c-Myb can be viewed as a block to differentiation our studies moved into two in vitro systems to evaluate effects of truncated forms of c-Myb on cytokine induced maturation of myeloid progenitors to the granulocyte and macrophage lineages. Deregulated expression of truncated and full length c-Myb did not result in maintenance of the myelomonocytic progenitor state but rather a. block in differentiation at intermediate to late steps in the maturation processes of myelomonocytic cells. Our results argue that inhibition of differentiation is due to c-Myb's ability to maintain the proliferative state of cells. Interestingly, the phenotype of continuously proliferating monocytic cells resembles that of the tumor cell phenotype, Recently we identified a new target of integration, MmlI, which is rearranged in ten promonocytic leukemias that do not have c-myb rearrangements. This locus which was mapped to chromosome 10 is presently being characterized. C1 TEMPLE UNIV,SCH MED,FELS INST CANC RES & MOL BIOL,PHILADELPHIA,PA 19140. RP Wolff, L (reprint author), NCI,GENET LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 33 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60414-6 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 211 BP 191 EP 199 PG 9 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BG27J UT WOS:A1996BG27J00019 PM 8585950 ER PT S AU Ohashi, T Masuda, M Ruscetti, SK AF Ohashi, T Masuda, M Ruscetti, SK BE Wolff, L Perkins, AS TI Activation of stat-related DNA-binding factors by erythropoietin and the spleen focus-forming virus SO MOLECULAR ASPECTS OF MYELOID STEM CELL DEVELOPMENT SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Molecular Aspects of Myeloid Stem Cell Development CY APR 30-MAY 03, 1995 CL ANNAPOLIS, MD SP Natl Canc Inst, AMGEN Inc, Bristol Myers Squibb Pharm Inst, Merck, Sandoz Res Inst, Bayer Corp, Upjohn Co ID PROTEIN-TYROSINE; RECEPTOR; ERYTHROLEUKEMIA; GLYCOPROTEIN; ASSOCIATION; INDUCTION; CELLS; JAK2; PHOSPHORYLATION; OLIGOMERIZATION RP Ohashi, T (reprint author), NCI,MOL ONCOL LAB,FREDERICK,MD 21702, USA. RI Ohashi, Takashi/C-4671-2012 OI Ohashi, Takashi/0000-0002-3769-4224 NR 33 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60414-6 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 211 BP 223 EP 231 PG 9 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BG27J UT WOS:A1996BG27J00022 PM 8585953 ER PT S AU Largaespada, DA Brannan, CI Shaughnessy, JD Jenkins, NA Copeland, NG AF Largaespada, DA Brannan, CI Shaughnessy, JD Jenkins, NA Copeland, NG BE Wolff, L Perkins, AS TI The neurofibromatosis type 1 (NF1) tumor suppressor gene and myeloid leukemia SO MOLECULAR ASPECTS OF MYELOID STEM CELL DEVELOPMENT SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Molecular Aspects of Myeloid Stem Cell Development CY APR 30-MAY 03, 1995 CL ANNAPOLIS, MD SP Natl Canc Inst, AMGEN Inc, Bristol Myers Squibb Pharm Inst, Merck, Sandoz Res Inst, Bayer Corp, Upjohn Co ID CHRONIC MYELOMONOCYTIC LEUKEMIA; MYELODYSPLASTIC SYNDROMES; RAS MUTATIONS; MICE; INTEGRATION; DISORDERS; PROTEINS; P21(RAS); CHILDREN; TISSUES AB Activating mutations of RAS genes are a common event in the genesis of a wide variety of human tumor types (for review see Barbacid 1990). It has also become increasingly clear that many tumors without RAS gene mutations have acquired genetic lesions that contribute to tumorigenesis by causing increased or prolonged activation of Ras. In this paper we review and describe studies using human and mouse cells on the association between NF1 gene loss and the development of myeloid leukemia. The NF1 gene product, neurofibromin, has GTPase activating protein (GAP) activity for Ras and thus, could negatively regulate Ras. Therefore, NF1 gene loss in myeloid cells may contribute to leukemogenesis by activating Ras. C1 UNIV FLORIDA,DEPT MOL GENET & MICROBIOL,GAINESVILLE,FL 32610. UNIV FLORIDA,CTR MAMMALIAN GENET,GAINESVILLE,FL 32610. RP Largaespada, DA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702, USA. RI Largaespada, David/C-9832-2014 NR 29 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60414-6 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 211 BP 233 EP 239 PG 7 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BG27J UT WOS:A1996BG27J00023 PM 8585954 ER PT S AU Hajra, A Liu, PP Collins, FS AF Hajra, A Liu, PP Collins, FS BE Wolff, L Perkins, AS TI Transforming properties of the leukemic inv(16) fusion gene CBFB-MYH11. SO MOLECULAR ASPECTS OF MYELOID STEM CELL DEVELOPMENT SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Molecular Aspects of Myeloid Stem Cell Development CY APR 30-MAY 03, 1995 CL ANNAPOLIS, MD SP Natl Canc Inst, AMGEN Inc, Bristol Myers Squibb Pharm Inst, Merck, Sandoz Res Inst, Bayer Corp, Upjohn Co ID ACUTE MYELOID-LEUKEMIA; MYOSIN HEAVY-CHAIN; CORE-BINDING-FACTOR; TRANSCRIPTION FACTOR; SMOOTH-MUSCLE; AML1; FAMILY; LOCALIZATION; BETA; DNA RP Hajra, A (reprint author), NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892, USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 23 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN 33 PA HEIDELBERGER PLATZ 3, W-1000 BERLIN 33, GERMANY SN 0070-217X BN 3-540-60414-6 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1996 VL 211 BP 289 EP 298 PG 10 WC Oncology; Cell Biology; Immunology; Microbiology SC Oncology; Cell Biology; Immunology; Microbiology GA BG27J UT WOS:A1996BG27J00029 PM 8585960 ER PT J AU Yokoyama, WM Reichlin, A Margulies, DH Smith, HRC AF Yokoyama, WM Reichlin, A Margulies, DH Smith, HRC TI MHC class I-dependent and -independent NK cell specificity SO MOLECULAR BASIS OF NK CELL RECOGNITION AND FUNCTION SE CHEMICAL IMMUNOLOGY LA English DT Review ID NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; LY-49 MULTIGENE FAMILY; MARROW GRAFT-REJECTION; BONE-MARROW; MOLECULAR-CLONING; CARBOHYDRATE-RECOGNITION; MONOCLONAL-ANTIBODY; P53-DEFICIENT MICE; MEMBRANE-PROTEINS C1 JEWISH HOSP ST LOUIS,DEPT MED,DIV RHEUMATOL,ST LOUIS,MO 63110. JEWISH HOSP ST LOUIS,DEPT PATHOL,ST LOUIS,MO 63110. NIH,IMMUNOL LAB,BETHESDA,MD 20892. RP Yokoyama, WM (reprint author), WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,DIV RHEUMATOL,660 S EUCLID AVE,CAMPUS BOX 8045,ST LOUIS,MO 63110, USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 88 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem.Immunol. PY 1996 VL 64 BP 1 EP 18 PG 18 WC Immunology SC Immunology GA BG58U UT WOS:A1996BG58U00001 PM 8942068 ER PT J AU Teplukhin, AV Zhurkin, VB Jernigan, R Poltev, VI AF Teplukhin, AV Zhurkin, VB Jernigan, R Poltev, VI TI Monte Carlo modeling of DNA hydration. Poly(A)-water interaction in the major groove stabilizes the B' conformation SO MOLECULAR BIOLOGY LA English DT Article DE nucleic acids; A tracts; poly(dA)center dot poly(dT); B'-DNA; DNA curvature; Monte Carlo method; hydration; water structure ID MINOR GROOVE; SIMULATION; CURVATURE; GEOMETRY; TRACTS; DUPLEX; SPINE; BASES; HELIX; BENT AB Hydration of two kinds of DNA duplex containing A tracts was assessed by Monte Carlo simulation. Conformations of B'-DNA with narrowed minor groove proved advantageous in the hydration energy over canonical B-DNA. The effect is mainly due to adenine-water interactions in the major groove. The energy of these interactions in the minor groove did not appreciably vary with groove width, while for the major groove the energy monotonically increased with widening at the expense of the other groove. Analysis of the H-bond networks in the duplex water jackets revealed that such dissimilar dependences are due to the structural peculiarities of water in the DNA grooves. Decisive for stabilization of the B' conformation is the rise in the number of water H-bonds with adenine N7 and generation of ''triples,'' i.e., formation by one water molecule of three H-bonds: two with N7 atoms of adjacent adenines and a third with the amino group in one of the latter. C1 RUSSIAN ACAD SCI,VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. RUSSIAN ACAD SCI,INST THEORET & EXPTL BIOPHYS,PUSHCHINO 142292,MOSCOW REG,RUSSIA. RP Teplukhin, AV (reprint author), RUSSIAN ACAD SCI,INST MATH PROBLEMS BIOL,PUSHCHINO 142292,MOSCOW REG,RUSSIA. RI Jernigan, Robert/A-5421-2012; Teplukhin, Alexander/J-9827-2012 OI Teplukhin, Alexander/0000-0002-3285-0240 NR 25 TC 10 Z9 10 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU 233 SPRING ST, NEW YORK, NY 10013 SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD JAN-FEB PY 1996 VL 30 IS 1 BP 75 EP 84 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK854 UT WOS:A1996UK85400001 ER PT B AU Linnekin, D Weiler, SR Mou, S DeBerry, CS Keller, JR Ruscetti, FW Ferris, DK Longo, DL AF Linnekin, D Weiler, SR Mou, S DeBerry, CS Keller, JR Ruscetti, FW Ferris, DK Longo, DL BE Abraham, NG Asano, S Brittinger, G Maestroni, GJM Shadduck, RK TI JAK2 is constitutively associated with c-kit and is phosphorylated in response to stem cell factor SO MOLECULAR BIOLOGY OF HEMATOPOIESIS 5 LA English DT Proceedings Paper CT 9th Symposium on Molecular Biology of Hematopoiesis and Treatment of Leukemias and Lymphomas CY JUN 23-27, 1995 CL GENOA, ITALY SP Menarini Int Fdn AB Stem cell factor (SCF) interacts with the receptor tyrosine kinase c-kit and has potent effects on hematopoiesis; We have examined the role of JAK2 in the SCF signal transduction pathway. JAK2 and c-kit were constitutively associated and treatment with SCF resulted in rapid and transient tyrosine phosphorylation of JAK2. Incubation of cells with JAK2 antisense oligonucleotides resulted in significant decreases in SCF-induced proliferation These data suggest that JAK2 plays a role in SCF-induced proliferation. RP Linnekin, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LAB LEUKOCYTE BIOL,BLDG 567,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45318-5 PY 1996 BP 369 EP 376 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Hematology; Transplantation SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Hematology; Transplantation GA BG81N UT WOS:A1996BG81N00045 ER PT J AU Andrews, KL Nettesheim, P Asai, DJ Ostrowski, LE AF Andrews, KL Nettesheim, P Asai, DJ Ostrowski, LE TI Identification of seven rat axonemal dynein heavy chain genes: Expression during ciliated cell differentiation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID TRACHEAL EPITHELIUM; AIRWAY EPITHELIUM; BINDING SITES; SEQUENCE; MICROCOMPUTER; EXPOSURE AB Axonemal dyneins are molecular motors that drive the beating of cilia and flagella. We report here the identification and partial cloning of seven unique axonemal dynein heavy chains from rat tracheal epithelial (RTE) cells. Combinations of axonemal-specific and degenerate primers to conserved regions around the catalytic site of dynein heavy chains were used to obtain cDNA fragments of rat dynein heavy chains. Southern analysis indicates that these are single copy genes, with one possible exception, and Northern analysis of RNA from RTE cells shows a transcript of similar to 15 kb for each gene. Expression of these genes was restricted to tissues containing axonemes (trachea, testis, and brain). A time course analysis during ciliated cell differentiation of RTE cells in culture demonstrated that the expression of axonemal dynein heavy chains correlated with the development of ciliated cells, while cytoplasmic dynein heavy chain expression remained constant. In addition, factors that regulate the development of ciliated cells in culture regulated the expression of axonemal dynein heavy chains in a parallel fashion. These are the first mammalian dynein heavy chain genes shown to be expressed specifically in axonemal tissues. Identification of the mechanisms that regulate the cell-specific expression of these axonemal dynein heavy chains will further our understanding of the process of ciliated cell differentiation. C1 NIEHS,PULM PATHOBIOL LAB,AIRWAY CELL BIOL GRP,RES TRIANGLE PK,NC 27709. PURDUE UNIV,DEPT BIOL SCI,W LAFAYETTE,IN 47907. FU NIGMS NIH HHS [GM-49889] NR 41 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JAN PY 1996 VL 7 IS 1 BP 71 EP 79 PG 9 WC Cell Biology SC Cell Biology GA TR507 UT WOS:A1996TR50700007 PM 8741840 ER PT J AU Csiszar, K Entersz, I Trackman, PC Samid, D Boyd, CD AF Csiszar, K Entersz, I Trackman, PC Samid, D Boyd, CD TI Functional analysis of the promoter and first intron of the human lysyl oxidase gene SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE lysyl oxidase; transcription; ras-regulation ID MENKES DISEASE; MESSENGER-RNA; RAT FIBROBLASTS; CANDIDATE GENE; COLLAGEN GENE; CELL-LINE; H-RAS; C-MYC; EXPRESSION; TRANSFORMATION AB Alterations in the synthesis and activity of lysyl oxidase occur concomitant with developmental changes in collagen and elastin deposition and with the pathogenesis of several acquired and heritable connective tissue disorders. To begin to unravel the mechanisms that control lysyloxidase gene expression, we have previously reported the complete exon-intron structure of the human lysyl oxidase gene. We have now sequenced this entire gene, including all six introns and 4 kb of DNA 5' of exon 1. Analysis of over 13 kb of intervening sequence and 5' flanking sequence revealed a concentration of conserved consensus sequence elements within the first intron and 1 kb immediately 5' of exon 1. Analysis of intron 1 and the 5' Banking domain, using recombinant plasmids containing the chloramphenicol acetyl transferase (CAT) reporter gene, identified functional DNA sequence elements within these non-coding domains responsible for inhibition and up-regulation of CAT activity in primary cultures of human skin fibroblasts, in smooth muscle cells, revertant cells derived from an osteosarcoma cell Line and malignant c-Ha-ras-transformed osteosarcoma cells. DNA sequence elements within intron I, in particular, resulted in a marked increase in CAT reporter activity in cultured fibroblasts, smooth muscle cells and osteosarcoma cells. In c-Ha-ras-transform osteosarcoma cells, however, no such enhancer activity of intron 1 sequence was observed. Ras-transformed osteosarcoma cells exhibited reduced steady-state levels of lysyl oxidase mRNA that was primarily controlled through reduced transcription of the lysyl oxidase gene. The lack of any up-regulation of CAT activity in these ras-transformed cells by sequence elements within intron 1 suggests a complex interaction between cis-acting domains and trans-acting transcriptional factors in the 5'promoter domain and the first intron of the lysyl oxidase gene. C1 BOSTON UNIV,SCH MED,GOLDMAN SCH GRAD DENT,BOSTON,MA 02118. NCI,CLIN PHARMACOL BRANCH,NIH,BETHESDA,MD 20892. RP Csiszar, K (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT SURG,NEW BRUNSWICK,NJ 08903, USA. FU NHLBI NIH HHS [HL 37438, HL 39869, HL 42798] NR 54 TC 22 Z9 23 U1 0 U2 0 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 1996 VL 23 IS 2 BP 97 EP 108 DI 10.1007/BF00424435 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VY626 UT WOS:A1996VY62600004 PM 8983023 ER PT J AU Borovitskaya, AE Evtushenko, VI Sabol, SL AF Borovitskaya, AE Evtushenko, VI Sabol, SL TI Gamma-radiation-induced cell death in the fetal rat brain possesses molecular characteristics of apoptosis and is associated with specific messenger RNA elevations SO MOLECULAR BRAIN RESEARCH LA English DT Article DE apoptosis; radiation; fetal rat brain; messenger RNA; p53; Fos; JunB; Bax ID WILD-TYPE P53; C-JUN; FOLLICULAR LYMPHOMA; IONIZING-RADIATION; RIBONUCLEIC-ACID; CEREBRAL-CORTEX; GROWTH-FACTORS; GENE; EXPRESSION; PROTEIN AB Low-dose ionizing irradiation of 16-18-day pregnant rats rapidly kills stem cells in the fetal forebrain. We have examined gamma-irradiated 17-day fetal rat brain tissue for molecular characteristics of apoptosis and changes in levels of mRNAs relevant to apoptosis. In many forebrain cells radiation elicits within 5 h nuclear condensation and fragmentation consistent with apoptosis. An electrophoretic DNA ladder indicative of internucleosomal chromatin cleavage was prominent within 3 h after irradiation. Pretreatment of pregnant rats with cycloheximide, or pretreatment of dissociated fetal brain cells in culture with actinomycin D, abolished the radiation-induced internucleosomal DNA fragmentation, demonstrating requirements for protein and RNA synthesis. Irradiation dramatically increased the level of the p53 transcription factor and the abundances of mRNAs coding for the cell-cycle inhibitor p21/Waf-1/Cip-1 and the AP-1-associated transcription factors Fos and JunB. Irradiation moderately increased the level of mRNA for the positive apoptosis regulator Bax. In contrast, irradiation reduced by 50-70% the abundances of most other mRNAs tested, including those for housekeeping proteins, p53, Jun, Myc, interleukin-1-beta-converting enzyme, and the negative apoptosis regulators Bcl-2 and Bcl-x(L). These results indicate that radiation-elicited apoptosis of fetal brain cells is associated with activation of the p53 system, probable increases in AP-1 Fos/JunB heterodimers, and an increased ratio of Bax to Bcl-2 + Bcl-x(L). C1 CENT INST ROENTGENOL & RADIOL, LAB GENET ENGN, ST PETERSBURG 189646, RUSSIA. RP Borovitskaya, AE (reprint author), NHLBI, LAB BIOCHEM GENET, BLDG 36, ROOM 1C-06, BETHESDA, MD 20892 USA. NR 69 TC 44 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JAN PY 1996 VL 35 IS 1-2 BP 19 EP 30 DI 10.1016/0169-328X(95)00177-T PG 12 WC Neurosciences SC Neurosciences & Neurology GA TU209 UT WOS:A1996TU20900003 ER PT J AU Acs, G Lee, J Marquez, VE Blumberg, PM AF Acs, G Lee, J Marquez, VE Blumberg, PM TI Distinct structure-activity relations for stimulation of Ca-45 uptake and for high affinity binding in cultured rat dorsal root ganglion neurons and dorsal root ganglion membranes SO MOLECULAR BRAIN RESEARCH LA English DT Article DE capsaicin; resiniferatoxin; vanilloid receptor; cultured neurons; dorsal root ganglia; rat; receptor subclasses ID VANILLOID CAPSAICIN RECEPTOR; SENSORY-EFFERENT FUNCTION; PRIMARY AFFERENT NEURONS; RESINIFERATOXIN BINDING; URINARY-BLADDER; CHEMICAL-STRUCTURE; SPINAL-CORD; COOPERATIVITY; CAPSAZEPINE; MECHANISMS AB The [H-3]resiniferatoxin (RTX) binding assay using membrane preparations has been used to identify and characterize the vanilloid receptors in the central and peripheral nervous system of different species. In the present study, using cultured adult rat dorsal root ganglion neurons either in suspension or attached to the tissue culture plates, we developed an assay to measure specific [H-3]RTX binding by the intact cells. We were able to characterize the vanilloid binding characteristics of the neurons and compared those to the properties of vanilloid binding sites present in rat dorsal root ganglia membrane preparations. We found that [H-3]RTX bound with similar affinity and positive cooperativity to attached neurons (cultured for 5 days before being assayed), neurons in suspension (using a filtration assay) and dorsal root ganglion membrane preparations. Dissociation constants obtained in the three assays were 47.6 +/- 3.5 pM, 38.4 +/- 3.1 pM and 42.6 +/- 3.1 pM, respectively. The cooperativity indexes determined by fitting the data to the Hill equation were 1.73 +/- 0.11, 1.78 +/- 0.12 and 1.78 +/- 0.09, respectively. The maximal binding capacity was 0.218 +/- 0.026 fmol/10(3) cells and 0.196 +/- 0.021 fmol/10(3) cells in the case of the attached cells and cells in suspension, respectively. Nonradioactive RTX, capsaicin, capsazepine and resiniferonol 20-homovanillylamide fully displaced specifically bound [H-3]RTX from cells in suspension with K-i and Hill coefficient values of 42.5 +/- 5.3 pM, 2.06 +/- 0.16 mu M, 3.16 +/- 0.21 mu M and 32.4 +/- 4.1 nM and 1.79 +/- 0.17, 1.68 +/- 0.06, 1.72 +/- 0.11 and 1.81 +/- 0.12, respectively. Structure-activity analysis of different vanilloid derivatives revealed that the various compounds have distinct potencies for receptor binding and inducing Ca-45 uptake in rat dorsal root ganglion neurons. Affinities for receptor binding and stimulation of Ca-45 uptake of RTX, resiniferonol 20-homovanillylamide, RTX-thiourea, tinyatoxin, phorbol 12,13-dibenzoate 20-homovanillylamide and capsaicin were 38.5 +/- 2.9 pM, 25.7 +/- 3.0 nM, 68.5 +/- 3.8 nM, 173 +/- 25 pM, 7.98 +/- 0.83 mu M and 4.93 +/- 0.35 mu M as compared to 0.94 +/- 0.12 nM, 26.5 +/- 3.5 nM, 149 +/- 30 nM, 1.46 +/- 0.25 nM, 1.41 +/- 0.48 mu M and 340 +/- 57 nM. Computer fitting of the data yielded Hill coefficient values indicating positive cooperativity of receptor binding; however, stimulation of Ca-45 uptake appeared to follow a non-cooperative mechanism of action. The competitive capsaicin antagonist capsazepine inhibited specific binding of [H-3]RTX by rat dorsal root ganglion membrane preparations with K-i and Hill coefficient values of 3.89 +/- 0.38 mu M and 1.74 +/- 0.11. On the other hand it inhibited the induction of Ca-45 uptake into the cells induced by capsaicin and RTX in a non-cooperative fashion with K-i values of 271 +/- 29 nM and 325 +/- 47 nM. Our results show that the membrane binding assay relates to the reality of receptor function in the intact, cultured neurons, both in terms of affinity and positive cooperativity. However the different vanilloid derivatives displayed markedly distinct structure-activity relations for high affinity receptor binding and stimulation of Ca-45 uptake into rat dorsal root ganglion neurons. Among various explanations for this discrepancy, we favor the possibility that the two assays detect distinct classes of the vanilloid (capsaicin) receptor present in primary sensory neurons. C1 NCI,DIV BASIC SCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. NCI,DIV BASIC SCI,MED CHEM LAB,BETHESDA,MD 20892. NR 49 TC 57 Z9 58 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JAN PY 1996 VL 35 IS 1-2 BP 173 EP 182 DI 10.1016/0169-328X(95)00204-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA TU209 UT WOS:A1996TU20900020 ER PT J AU Zhang, LX Smith, MA Kim, SY Rosen, JB Weiss, SRB Post, RM AF Zhang, LX Smith, MA Kim, SY Rosen, JB Weiss, SRB Post, RM TI Changes in cholecystokinin mRNA expression after amygdala kindled seizures: An in situ hybridization study SO MOLECULAR BRAIN RESEARCH LA English DT Article DE kindling; in situ hybridization; cholecystokinin; seizure; electroconvulsive seizure ID ACID-INDUCED SEIZURES; OCTAPEPTIDE CCK-8; RAT-BRAIN; HIPPOCAMPUS; ENKEPHALIN; MORPHINE; PREPROCHOLECYSTOKININ; IMMUNOREACTIVITIES; LOCALIZATION; SOMATOSTATIN AB Cholecystokinin (CCK) can be a potent anticonvulsant neuropeptide in certain seizure models. Therefore, we examined whether seizures produced by electrical kindling of the amygdala or electroconvulsive seizures (ECS) would affect the expression of CCK mRNA in rat brain. Following a single kindled seizure, CCK mRNA expression was decreased about 20-58% in the amygdala. In contrast, after multiple consecutive kindled seizures, CCK mRNA expression was increased in the amygdala, cerebral cortex, CA1 pyramidal cell layer of the hippocampus and dentate hilus. A single ECS produced no effect on CCK mRNA expression, but multiple ECS increased expression in the interneurons of the hippocampus 24 h after the last seizure. Since seizures produced by ECS can be anticonvulsant to further ECS or kindled seizures, the CCK increases in the hippocampus may represent a compensatory anticonvulsant adaptation observed in both models. Overall, the kindling-induced alterations in CCK expression appear to be more complex involving multiple brain regions and distinct temporal properties. RP Zhang, LX (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 20 Z9 22 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JAN PY 1996 VL 35 IS 1-2 BP 278 EP 284 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TU209 UT WOS:A1996TU20900031 ER PT J AU Kaech, S Kim, JB Cariola, M Ralston, E AF Kaech, S Kim, JB Cariola, M Ralston, E TI Improved lipid-mediated gene transfer into primary cultures of hippocampal neurons SO MOLECULAR BRAIN RESEARCH LA English DT Article DE transfection; neuronal culture; hippocampus; liposomes; beta-galactosidase ID CENTRAL-NERVOUS-SYSTEM; BETA-GALACTOSIDASE; EXPRESSION; RECEPTOR; VECTOR; CELLS AB We have examined lipids as transfection agents to introduce recombinant plasmids into primary cultures of rat hippocampal neurons. By modifying the protocol for transfection mediated by the commercial reagent DOTAP, we were able to achieve a transfection efficiency of about 3%. Expression of various transfected gene products was sustained for several weeks in culture, the neurons developed normally and the transfected gene products were targeted to the appropriate subcellular compartment. C1 NINCDS,NEUROBIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 22 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JAN PY 1996 VL 35 IS 1-2 BP 344 EP 348 DI 10.1016/0169-328X(95)00238-N PG 5 WC Neurosciences SC Neurosciences & Neurology GA TU209 UT WOS:A1996TU20900042 ER PT J AU Chen, H Zhang, L Rubinow, DR Chuang, DM AF Chen, H Zhang, L Rubinow, DR Chuang, DM TI Chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA and binding sites in various regions of the rat hippocampus (vol 32, pg 348, 1995) SO MOLECULAR BRAIN RESEARCH LA English DT Correction, Addition C1 NIMH,BIOL PSYCHIAT BRANCH,SECT BEHAV ENDOCRINOL,BETHESDA,MD 20892. RP Chen, H (reprint author), NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JAN PY 1996 VL 35 IS 1-2 BP 359 EP 359 PG 1 WC Neurosciences SC Neurosciences & Neurology GA TU209 UT WOS:A1996TU20900045 ER PT J AU Kenney, NJ Smith, GH Maroulakou, IG Green, JH Muller, WJ Callahan, R Salomon, DS Dickson, RB AF Kenney, NJ Smith, GH Maroulakou, IG Green, JH Muller, WJ Callahan, R Salomon, DS Dickson, RB TI Detection of amphiregulin and Cripto-1 in mammary tumors from transgenic mice SO MOLECULAR CARCINOGENESIS LA English DT Article DE growth factors; transgenic mouse; mammary cancer; amphiregulin; Cripto-1 ID EPIDERMAL GROWTH-FACTOR; BREAST-CANCER; EPITHELIAL-CELLS; FACTOR RECEPTOR; EXPRESSION; GENE; INDUCTION; ONCOGENE; FAMILY; ALPHA AB Epidermal growth factor family members are widely expressed in human breast cancer and are thought to play an important dual role in mammary gland development and tumorigenesis. Overexpression of two relatively new members of this family, amphiregulin (AR) and Cripto-1 (CR-1), has been previously shown to transform immortalized human and mouse mammary epithelial cells. Here, we extend these results and address the dysregulated expression of AR and CR-1 in many types of transgenic neoplastic mouse mammary tissues. Transgenic mouse strains overexpressing the oncogenes transforming growth factor-alpha, neu, int-3, polyoma virus middle T antigen, and simian virus 40 large T antigen have been previously shown to develop spontaneous mammary neoplasia. These models were each examined for mammary-tumor expression of AR and CR-1 by reverse transcription-polymerase chain reaction, western blot, and immunocytochemical analyses. Mammary tumors from each source expressed AR and CR-1. Western blot analysis revealed that, in all mammary tumors, AR and CR-1 protein species were processed differently than in virgin and lactating mouse mammary tissue. In addition, immunohistochemical detection of AR and CR-I in tumor tissue revealed different patterns of growth-factor localization in different types of transgenic mouse mammary-derived tumors. These findings are consistent with the possibility of widespread roles for AR and CR-1 in the promotion and/or progression stages of mouse mammary tumorigenesis. (C) 1996 Wiley-Liss, Inc. C1 GEORGETOWN UNIV,LOMBARDI CANC CTR,WASHINGTON,DC 20007. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,CANC RES & DEV CTR,FREDERICK,MD 21701. MCMASTER UNIV,INST MOLEC BIOL & BIOTECHNOL,HAMILTON,ON,CANADA. NR 37 TC 42 Z9 42 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 1996 VL 15 IS 1 BP 44 EP 56 PG 13 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA TR176 UT WOS:A1996TR17600007 PM 8561865 ER PT J AU Ohmori, M Shimura, H Shimura, Y Kohn, LD AF Ohmori, M Shimura, H Shimura, Y Kohn, LD TI A Y-box protein is a suppressor factor that decreases thyrotropin receptor gene expression SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RAT-THYROID CELLS; C-MYC GENE; BINDING-PROTEIN; H-DNA; CHROMOSOMAL LOCALIZATION; PROMOTER INTERACTS; RESPONSE ELEMENT; CDNA SEQUENCE; FRTL-5 CELLS; MALIC ENZYME AB The decanucleotides in a tandem repeat, -162 to -140 bp, are suppressor elements that decrease TSH receptor (ISHR) gene expression by different mechanisms. A factor(s) interacting with the 3'-decanucleotide compete for proteins that bind the cAMP response element, -139 to -132 bp, a constitutive enhancer necessary for efficient TSHR expression. The 5'-decanucleotide is in a CT-rich, S1 nuclease-sensitive region of the promoter; its suppressor activity has been related to its ability to bind a nonthyroid-specific protein to its coding strand. In this report we clone a complementary DNA encoding a single strand DNA-binding protein that forms a specific protein-DNA complex with the coding strand of the 5'- but not the 3'-decanucleotide and not with the 5'-decanucleotide noncoding or double strand. We show, by cotransfection with TSHR promoter-chloramphenicol acetyltransferase chimeras, that the protein is a suppressor that regulates the function of the 5'- but not the 3'-decanucleotide. The protein is a Y-box protein that was previously cloned as an enhancer factor from the rat liver; it is, however, 95% identical to human YB-1, which suppresses major histocompatibility class II gene expression, and to human nuclease-sensitive element protein-1, a Y-box protein identified by its ability to bind single strand, CT-rich, nuclease-sensitive elements of genes that, like the TSHR, have CC-rich promoters. Unexpectedly, the Y-box protein binds two other sites in the minimal TSHR promoter in a single strand-specific fashion and acts a suppressor at each of these sites. One is associated with the insulin response element of the minimal TSHR promoter and is not in an overtly CT-rich region. The other is located 3' to the cAMP response element in a region termed the S-box, -120 to -113 bp, because of its homology to the S-box of the major histocompatibility class II promoter; this site is in a CT-rich area and, as in the class II promoter, is linked to cAMP-induced gene suppression. A conserved CCTC sequence in each site is important for the binding and suppressor function of the Y-box protein. C1 NIDDKD, DEPT BIOCHEM & METAB, CELL REGULAT SECT, BIOCHEM & METAB LAB, BETHESDA, MD 20892 USA. NR 45 TC 36 Z9 37 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 1996 VL 10 IS 1 BP 76 EP 89 DI 10.1210/me.10.1.76 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TP323 UT WOS:A1996TP32300008 PM 8838147 ER PT J AU Minta, JO Wong, MJ Kozak, CA KunnathMuglia, LM Goldberger, G AF Minta, JO Wong, MJ Kozak, CA KunnathMuglia, LM Goldberger, G TI cDNA cloning, sequencing and chromosomal assignment of the gene for mouse complement factor I (C3b/C4b inactivator): Identification of a species specific divergent segment in factor I SO MOLECULAR IMMUNOLOGY LA English DT Article DE complement factor I; evolution; mouse chromosome ID AMINO-ACID-SEQUENCE; LDL-RECEPTOR; C3B INACTIVATOR; FACTOR-X; BLOOD-COAGULATION; MESSENGER-RNA; COMPONENT C-3; ALPHA-SUBUNIT; BETA-SUBUNIT; PROTEIN C8 AB Factor I is an essential regulatory serine proteinase of the complement cascade. It cleaves and inactivates the C3b and C4b constituents of the C3 and C5 convertases and thereby regulates many complement-mediated activities. The human protein is a heterodimer composed of a 50 kDa non-catalytic subunit (which contains several domains, i.e. FIM, CD5, LDLr type A) disulfide linked to a 38 kDa catalytic subunit. Recent characterization of Xenopus factor I cDNA revealed a 29 residue negatively charged region in its heavy chain which is absent in the human protein (Kunnath-Muglia et al., Molec. Immun. 30, 1249-1256, 1993). We report the complete cDNA sequence of mouse factor I as well as a partial chicken factor I cDNA sequence. Alignment of these two sequences with the published sequences for human and Xenopus proteins (a) demonstrates an overall conservation of primary structure and domain organization of mouse factor I, and (b) defines a divergent segment (D segment) in each species. In Xenopus protein, the D segment includes the 29 residue negatively charged region. In each of the four species examined, the D segment differed in length, sequence, organization, and number of repeated subregions. These differences reflect a considerable evolution of D segment. The significance of the diversity of the D segment is at present unclear. We also report the chromosomal localization of the mouse factor I gene (Cfi) to distal chromosome 3 near Egf. C1 NIAID,BETHESDA,MD 20892. CHILDRENS HOSP,DIV INFECT DIS,BOSTON,MA 02115. CAMBRIDGE HOSP,DEPT PSYCHIAT,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,BOSTON,MA. RP Minta, JO (reprint author), UNIV TORONTO,DEPT CELLULAR & MOLEC PATHOL,100 COLL ST,TORONTO,ON M5S 1A8,CANADA. NR 52 TC 34 Z9 37 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 1996 VL 33 IS 1 BP 101 EP 112 DI 10.1016/0161-5890(95)00116-6 PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA TZ850 UT WOS:A1996TZ85000011 PM 8604219 ER PT J AU Ouaaz, P Ruscetti, FW Dugas, B Mikovits, J Agut, H Debre, P Mossalayi, MD AF Ouaaz, P Ruscetti, FW Dugas, B Mikovits, J Agut, H Debre, P Mossalayi, MD TI Role of IgE immune complexes in the regulation of HIV-1 replication and increased cell death of infected U1 monocytes: Involvement of CD23/Fc epsilon RII-mediated nitric oxide and cyclic AMP pathways SO MOLECULAR MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LOW AFFINITY RECEPTOR; MONONUCLEAR PHAGOCYTES; MAST-CELLS; CD23; MACROPHAGES; ACTIVATION; SYNTHASE; FC-EPSILON-R2; AMPLIFICATION AB Background: IgE/anti-IgE immune complexes (IgE-IC) induce the release of multiple mediators from monocytes/macrophages and the monocytic cell line U937 following the ligation of the low-affinity Fc epsilon receptors (Fc epsilon RII/CD23). These effects are mediated through an accumulation of cAMP and the generation of L-arginine-dependent nitric oxide (NO). Since high IgE levels predict more rapid progression to acquired immunodeficiency syndrome, we attempted to define the effects of IgE-IC on human immunodeficiency virus (HIV) production in monocytes. Materials and Methods: Two variants of HIV-1 chronically infected monocytic U1 cells were stimulated with IgE-IC and virus replication was quantified. NO and cAMP involvement was tested through the use of agonistic and antagonistic chemicals of these two pathways. Results: IgE-IC induced p24 production by U1 cells with low-level constitutive expression of HIV-1 mRNAs and extracellular HIV capsid protein p24 levels (U1(low)), upon their pretreatment with interleukin 4 (LL-4) or IL-13. This effect was due to the crosslinking of CD23, as it was reversed by blocking the IgE binding site on CD23. The IgE-IC effect could also be mimicked by crosslinking of CD23 by a specific monoclonal antibody. p24 induction by IgE-IC was then shown to be due to CD23-mediated stimulation of cAMP, NO, and tumor necrosis factor a (TNF alpha) generation. In another variant of U1 cells with >1 log higher constitutive production of p24 levels (Ul(high)), IgE-IC addition dramatically deceased all cell functions tested and accelerated cell death. This phenomenon was reversed by blocking the nitric oxide generation Conclusions: These data point out a regulatory role of IgE-IC on HIV-1 production in monocytic cells, through CD23-mediated stimulation of cAMP and NO pathways. IgE-IC can also stimulate increased cell death in high HIV producing cells through the NO pathway. C1 HOP LA PITIE SALPETRIERE, GRP IMMUNOHEMATOL MOL, CNRS, URA 625, F-75013 PARIS, FRANCE. HOP LA PITIE SALPETRIERE, DEPT VIROL, CNRS, EP 57, F-75013 PARIS, FRANCE. NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NR 63 TC 0 Z9 0 U1 0 U2 0 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 1996 VL 2 IS 1 BP 38 EP 49 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA TZ456 UT WOS:A1996TZ45600006 ER PT J AU Partin, KM Mayer, ML AF Partin, KM Mayer, ML TI Negative allosteric modulation of wild-type and mutant AMPA receptors by GYKI 53655 SO MOLECULAR PHARMACOLOGY LA English DT Article ID GLUTAMATE RECEPTORS; HIPPOCAMPAL-NEURONS; CYCLOTHIAZIDE; KAINATE; 2,3-BENZODIAZEPINE; DESENSITIZATION; RESPONSES; CHANNELS; ACID AB Benzothiadiazides such as cyclothiazide potentiate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor responses, whereas 2,3-benzodiazepines such as 1-(4-aminophenyl)-3-methylcarbamyl-4-methyl-7,8-methylenedioxy-3-4-dihydro-5H-2,3-benzodiazepine (GYKI 53655) act as noncompetitive antagonists; both drugs act through allosteric modulation. Controversy exists as to whether cyclothiazide and GYKI 53655 act at a common site. Recent mutational analysis has led to the identification of a serine residue in flip splice variants that is critical for directing the interaction of cyclothiazide with AMPA receptors. We tested whether the mutation of this residue to glutamine, which abolishes potentiation by cyclothiazide, can in addition block antagonism by 2,3-benzodiazepines, as would be predicted for action at a common site. We found that the S to Q mutation does not alter antagonism by 2,3-benzodiazepines, suggesting. that the molecular determinants directing the interaction between GYKI 53655 and AMPA receptors are not identical to those controlling sensitivity to cyclothiazide. Additional support for this was obtained from analysis of the responses of AMPA receptor flip/flop splice variants, which, despite differences in equilibrium desensitization and sensitivity to cyclothiazide, show only small differences in sensitivity to 2,3-benzodiazepines. Furthermore, introduction of the flip exon from GluRA into GluR6, conferred sensitivity to cyclothiazide but did not increase sensitivity to 2,3-benzodiazepines. Of interest, experiments with native AMPA receptors generated from hippocampal and forebrain poly(A)(+) mRNA revealed greater sensitivity to 2,3-benzodiazepines than receptors generated by expression of recombinant AMPA receptors, possibly indicating the existence of an unidentified accessory protein or novel receptor subunit. C1 NICHHD,LCMN,BETHESDA,MD 20892. RI Mayer, Mark/H-5500-2013; Partin, Kathryn/A-8706-2015 OI Partin, Kathryn/0000-0003-3801-3299 NR 32 TC 55 Z9 55 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 1996 VL 49 IS 1 BP 142 EP 148 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TR467 UT WOS:A1996TR46700018 PM 8569699 ER PT B AU Hauser, SE Berman, LE Thoma, GR AF Hauser, SE Berman, LE Thoma, GR BE Kuo, CCJ TI Performance of RAID as a storage system for Internet image delivery SO MULTIMEDIA STORAGE AND ARCHIVING SYSTEMS SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Multimedia Storage and Archiving Systems CY NOV 18-19, 1996 CL BOSTON, MA SP Soc Photo Opt Instrumentat Engineers DE RAID performance; storage subsystems performance; Internet applications AB Redundant Array of Inexpensive Disks (RAID) vendors rely on multi-megabyte files and large numbers of physical disks to achieve the high transfer rates and Input/Output Operations Per Second (IOPS) quoted in the promotional literature. Practical image database applications do not always deliver such large files and cannot always afford the cost of the large numbers of disks required to match the vendors' performance claims. Because the user is often waiting on-line to view the images, applications deployed on the World Wide Web (WWW) are especially sensitive to keeping inline images relatively small. For such applications, the expected performance advantages of RAID storage may not be achieved. The Lister Hill National Center for Biomedical Communications houses three image datasets on a SPARC storage Array RAID system. Applications deliver these images to users via the Internet using the WWW and other client/server programs. Although approximately 3% of the images exceed 1 MB in size, the average file size is less than 200 KB and approximately 60% of the files are less than 100 KB in size. A study was undertaken to determine the configuration of the RAID system that will provide the fastest retrieval of these image files and to discover general principles of RAID performance. Average retrieval times with single processes and with concurrent processes are measured and compared for several configurations of RAID levels 5 and 0+1. A few trends have emerged showing a tradeoff between optimally configuring the RAID for a single process or for concurrent processes. RP Hauser, SE (reprint author), NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,BETHESDA,MD 20894, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-2318-1 J9 P SOC PHOTO-OPT INS PY 1996 VL 2916 BP 14 EP 22 DI 10.1117/12.257289 PG 9 WC Computer Science, Information Systems; Optics SC Computer Science; Optics GA BG67L UT WOS:A1996BG67L00002 ER PT S AU Wolff, J AF Wolff, J BE Nagataki, S Yamashita, S TI Iodide prophylaxis for reactor accidents SO NAGASAKI SYMPOSIUM - RADIATION AND HUMAN HEALTH: PROPOSAL FROM NAGASAKI SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT Nagasaki Symposium on Radiation and Human Health - Proposal from Nagasaki, 50th Anniversary Meeting of the Atomic Bombing in Nagasaki CY SEP 19, 1995 CL NAGASAKI, JAPAN SP Nagasaki Med Assoc Hibakushas Med Care DE potassium iodide, thyroid blockade; Chernobyl; thyroid inhibitors; iodolactones; 2-iodohexadecanal C1 NIDDKD,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-82287-9 J9 INT CONGR SER PY 1996 VL 1103 BP 227 EP 237 PG 11 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA BG26B UT WOS:A1996BG26B00018 ER PT J AU McCloud, TG Klueh, PA Pearl, KC Cartner, LK Muschik, GM Poole, KK AF McCloud, TG Klueh, PA Pearl, KC Cartner, LK Muschik, GM Poole, KK TI Isolation of illudin S from the mature basidiocarp of Omphalotus illudens, and isolation of illudins S and M from the fermentation broth of Omphalotus olearis SO NATURAL PRODUCT LETTERS LA English DT Article DE Omphalotus illudens; Omphalotus olearis; illudin M; illudin S; analytical HPLC; fermentation ID PRECLINICAL EVALUATION; ANTICANCER AGENTS AB The cytotoxic sesquiterpene illudin S was isolated from the fruiting body of the fungus Omphalotus illudens. From the fermentation broth of Omphalotus olearis, ATCC-11719, both illudin S and illudin M were isolated. Normal and reverse phase HPLC analytical methods for the title compounds were developed. C1 SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FERMENTAT PROD FACIL,FREDERICK,MD 21702. NR 13 TC 8 Z9 8 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1057-5634 J9 NAT PROD LETT JI Nat. Prod. Lett. PY 1996 VL 9 IS 2 BP 87 EP 95 DI 10.1080/10575639608044931 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA WD874 UT WOS:A1996WD87400002 ER PT J AU Bokesch, HR McKee, TC Currens, MJ Gulakowski, RJ McMahon, JB Cardellina, JH Boyd, MR AF Bokesch, HR McKee, TC Currens, MJ Gulakowski, RJ McMahon, JB Cardellina, JH Boyd, MR TI HIV-inhibitory gallotannins from Lepidobotrys staudtii SO NATURAL PRODUCT LETTERS LA English DT Article DE Lepidobotrys staudtii; galloylquinic acid; HIV-2 inhibitory tannins ID REVERSE-TRANSCRIPTASE; ACID AB Three galloylquinic acids, 1,3,4,5-tetra-O-galloylquinic acid (1), 3,4,5-tri-O-galloylquinic acid (2), and methyl 3,4,5-tri-O-galloylquinate (3) were isolated from the stem bark of the monotypic plant Lepidobotrys staudtii. Compound 1 protected target cells from the cytopathic effects of HIV-1 and HIV-2 and also exhibited potent inhibition of cellular DNA polymerases, as well as of the reverse transcriptases of HIV-1 and HIV-2, but not of other retroviruses tested. C1 NCI,DIV CANC TREATMENT DIAG & CTR,DEV THERAPEUT PROGRAM,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD 21702. NR 9 TC 13 Z9 13 U1 0 U2 3 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1057-5634 J9 NAT PROD LETT JI Nat. Prod. Lett. PY 1996 VL 8 IS 2 BP 133 EP 136 DI 10.1080/10575639608043252 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA UG385 UT WOS:A1996UG38500009 ER PT J AU Fuller, RW Cardellina, JH Boyd, MR AF Fuller, RW Cardellina, JH Boyd, MR TI HIV-inhibitory natural products .28. Diterpene carboxylic acid from fruits of Xylopia sp SO NATURAL PRODUCT LETTERS LA English DT Article DE HIV-inhibitory; kaurane; diterpene acid; Xylopia sp AB A new kaurane diterpene was isolated and identified as the major HIV-inhibitory constituent of the aqueous extract of fruits of a Xylopia sp. plant. Analysis of spectral data revealed the structure of the compound, xylopinic acid (1), a new diastereomer of a compound previously known only as a chemical/microbial transformation product. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 13 TC 6 Z9 6 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1057-5634 J9 NAT PROD LETT JI Nat. Prod. Lett. PY 1996 VL 8 IS 3 BP 169 EP 172 DI 10.1080/10575639608044890 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA UH942 UT WOS:A1996UH94200003 ER PT S AU Kisilevsky Blake Pepys Damas Kirschner Costa Lundgren Benson Merlini Caughey Kelly AF Kisilevsky Blake Pepys Damas Kirschner Costa Lundgren Benson Merlini Caughey Kelly GP CIBA FDN TI Fibril structure - General discussion I SO NATURE AND ORIGIN OF AMYLOID FIBRILS SE CIBA FOUNDATION SYMPOSIA LA English DT Editorial Material CT Symposium on the Nature and Origin of Amyloid Fibrils CY OCT 23-25, 1995 CL OEIRAS, PORTUGAL SP Ciba Fdn, Gulbenkian Fdn, Inst Sci Oeiras C1 UMEA UNIV, DEPT CELL & MOL BIOL, S-90187 UMEA, SWEDEN. TEXAS A&M UNIV, DEPT CHEM, COLLEGE STN, TX 77843 USA. UNIV MASSACHUSETTS, DEPT SCI BIOL, LOWELL, MA 01854 USA. HAMMERSMITH HOSP, ROYAL POSTGRAD MED SCH, IMMUNOL MED UNIT, LONDON W12 0NN, ENGLAND. VET AFFAIRS MED CTR, INDIANA UNIV, SCH MED, DEPT MED, DIV RHEUMATOL, INDIANAPOLIS, IN 46202 USA. UNIV OXFORD, MOL BIOPHYS LAB, OXFORD OX1 3QU, ENGLAND. UNIV OXFORD, OXFORD CTR MOL SCI, OXFORD OX1 3QU, ENGLAND. NIAID, PERSISTENT VIRAL DIS LAB, NIH, ROCKY MT LABS, HAMILTON, MT 59840 USA. HOSP ST ANTONIO, CTR ESTUDOS PARAMILOIDOSE, P-4100 OPORTO, PORTUGAL. UNIV PORTO, INST CIENCIAS BIOMED ABEL SALAZAR, P-4050 OPORTO, PORTUGAL. UNIV PAVIA, HOSP IRCCS S MATTEO, RES LAB BIOTECHNOL, INST MED CLIN 2, I-27100 PAVIA, ITALY. RP Kisilevsky (reprint author), QUEENS UNIV, DEPT PATHOL, KINGSTON, ON K7L 3N6, CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER, WEST SUSSEX, ENGLAND PO19 1UD SN 0300-5208 BN 0-471-96361-5 J9 CIBA F SYMP PY 1996 VL 199 BP 40 EP 44 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Medicine, General & Internal; Neurosciences SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; General & Internal Medicine; Neurosciences & Neurology GA BG31D UT WOS:A1996BG31D00003 ER PT S AU Caughey Prusiner AF Caughey Prusiner GP CIBA FDN TI Cell-free conversion of protease-sensitive prion protein to the protease-resistant state: Requirement for aggregates of scrapie-associated prion protein - General discussion IV SO NATURE AND ORIGIN OF AMYLOID FIBRILS SE CIBA FOUNDATION SYMPOSIA LA English DT Editorial Material CT Symposium on the Nature and Origin of Amyloid Fibrils CY OCT 23-25, 1995 CL OEIRAS, PORTUGAL SP Ciba Fdn, Gulbenkian Fdn, Inst Sci Oeiras ID DISEASES; BIOLOGY; MODEL C1 UNIV CALIF SAN FRANCISCO,DEPT NEUROL BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. RP Caughey (reprint author), NIAID,LAB PERSISTENT VIRAL DIS,NIH,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA BAFFINS LANE, CHICHESTER, WEST SUSSEX, ENGLAND PO19 1UD SN 0300-5208 BN 0-471-96361-5 J9 CIBA F SYMP PY 1996 VL 199 BP 202 EP 204 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Medicine, General & Internal; Neurosciences SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; General & Internal Medicine; Neurosciences & Neurology GA BG31D UT WOS:A1996BG31D00017 ER PT J AU Permutt, MA Ghosh, S AF Permutt, MA Ghosh, S TI Rat model contributes new loci for NIDDM susceptibility in man SO NATURE GENETICS LA English DT Editorial Material ID DIABETES-MELLITUS C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Permutt, MA (reprint author), WASHINGTON UNIV,SCH MED,DIV ENDOCRINOL DIABET & METAB,660 S EUCLID,BOX 8127,ST LOUIS,MO 63110, USA. NR 15 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1996 VL 12 IS 1 BP 4 EP 6 DI 10.1038/ng0196-4 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA TM555 UT WOS:A1996TM55500003 PM 8528249 ER PT J AU Guan, XY Zhang, H Bittner, M Jiang, Y Meltzer, P Trent, J AF Guan, XY Zhang, H Bittner, M Jiang, Y Meltzer, P Trent, J TI Chromosome arm painting probes SO NATURE GENETICS LA English DT Letter ID INSITU HYBRIDIZATION; GENERATION; LIBRARIES RP Guan, XY (reprint author), NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892, USA. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 10 TC 82 Z9 85 U1 0 U2 4 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1996 VL 12 IS 1 BP 10 EP 11 DI 10.1038/ng0196-10 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA TM555 UT WOS:A1996TM55500006 PM 8528238 ER PT J AU DeLaurenzi, V Rogers, GR Hamrock, DJ Marekov, LN Steinert, PM Compton, JG Markova, N Rizzo, WB AF DeLaurenzi, V Rogers, GR Hamrock, DJ Marekov, LN Steinert, PM Compton, JG Markova, N Rizzo, WB TI Sjogren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene SO NATURE GENETICS LA English DT Article ID CULTURED FIBROBLASTS; ALCOHOL; OXIDOREDUCTASE AB Sjogren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder characterized by mental retardation, spasticity and ichthyosis, SLS patients have a profound deficiency in fatty aldehyde dehydrogenase (FALDH) activity. We have now cloned the human FALDH cDNA and show that it maps to the SLS locus on chromosome 17p11.2. Sequence analysis of FALDH amplified from fibroblast mRNA and genomic DNA from 3 unrelated SLS patients reveals distinct mutations, including deletions, an insertion and a point mutation. The cloning of FALDH and the identification of mutations in SLS patients opens up possibilities for developing therapeutic approaches to ameliorate the neurologic and cutaneous symptoms of the disease. C1 NIAMSD,SKIN BIOL LAB,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,IST DERMOPAT DELL IMMACOLATA IRCCS,DEPT EXPTL MED,BIOCHEM LAB,I-00167 ROME,ITALY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. FU NCRR NIH HHS [M01 RR00065] NR 22 TC 169 Z9 169 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1996 VL 12 IS 1 BP 52 EP 57 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA TM555 UT WOS:A1996TM55500014 PM 8528251 ER PT J AU Benjamin, J Li, L Patterson, C Greenberg, BD Murphy, DL Hamer, DH AF Benjamin, J Li, L Patterson, C Greenberg, BD Murphy, DL Hamer, DH TI Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking SO NATURE GENETICS LA English DT Letter ID VARIANTS; TRAITS C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 29 TC 823 Z9 846 U1 6 U2 43 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1996 VL 12 IS 1 BP 81 EP 84 DI 10.1038/ng0196-81 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TM555 UT WOS:A1996TM55500019 PM 8528258 ER PT J AU Zuo, L Weger, J Yang, QB Goldstein, AM Tucker, MA Walker, GJ Hayward, N Dracopoli, NC AF Zuo, L Weger, J Yang, QB Goldstein, AM Tucker, MA Walker, GJ Hayward, N Dracopoli, NC TI Germline mutations in the p16(INK4a) binding domain of CDK4 in familial melanoma SO NATURE GENETICS LA English DT Letter ID RET PROTOONCOGENE C1 SEQUANA THERAPEUT INC,LA JOLLA,CA 92037. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. QUEENSLAND INST MED RES,HERSTON,QLD 4029,AUSTRALIA. RI Tucker, Margaret/B-4297-2015; hayward, nicholas/C-1367-2015 OI hayward, nicholas/0000-0003-4760-1033 NR 30 TC 511 Z9 517 U1 2 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1996 VL 12 IS 1 BP 97 EP 99 DI 10.1038/ng0196-97 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA TM555 UT WOS:A1996TM55500024 PM 8528263 ER PT J AU Accili, D Drago, J Lee, EJ Johnson, MD Cool, MH Salvatore, P Asico, LD Jose, PA Taylor, SI Westphal, H AF Accili, D Drago, J Lee, EJ Johnson, MD Cool, MH Salvatore, P Asico, LD Jose, PA Taylor, SI Westphal, H TI Early neonatal death in mice homozygous for a null allele of the insulin receptor gene SO NATURE GENETICS LA English DT Letter ID GROWTH FACTOR-I; SUBSTRATE PHOSPHORYLATION; TYROSINE KINASE; BETA-SUBUNIT; AUTOPHOSPHORYLATION; MUTATION; LEPRECHAUNISM; EXPRESSION; BINDING; IGF-1 C1 NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20007. RP Accili, D (reprint author), NIDDKD,DIABET BRANCH,BETHESDA,MD 20892, USA. OI SALVATORE, Paola/0000-0002-7294-9253 NR 29 TC 354 Z9 365 U1 1 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 1996 VL 12 IS 1 BP 106 EP 109 DI 10.1038/ng0196-106 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TM555 UT WOS:A1996TM55500027 PM 8528241 ER PT J AU Schupke, H Bauer, C McNeilly, PJ Hempel, R Strong, J Kupferberg, HJ Kronbach, T AF Schupke, H Bauer, C McNeilly, PJ Hempel, R Strong, J Kupferberg, HJ Kronbach, T TI N-glucuronidation as a major metabolic pathway of the new anticonvulsant D-23129 in rats, dogs and man SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 ARZNEIMITTELWERK DRESDEN GMBH,DEPT BIOCHEM,CORP R&D ASTA MED GRP,DRESDEN,GERMANY. US FDA,DIV CLIN PHARMACOL,ROCKVILLE,MD 20850. NINCDS,NIH,EPILEPSY BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PY 1996 VL 354 IS 4 SU 1 BP 170 EP 170 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VN593 UT WOS:A1996VN59300168 ER PT J AU Striker, LJ Striker, GE AF Striker, LJ Striker, GE TI Glomerular sclerosis: An historical review SO NEPHROLOGIE LA French DT Review RP Striker, LJ (reprint author), NIDDK,KINGS COLL,RENAL CELL BIOL SECT,ROOM 3 NIIO,NIH MSC 1268,BETHESDA,MD 20892, USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78 AVE ROSERALE, 1211 GENEVA 4, SWITZERLAND SN 0250-4960 J9 NEPHROLOGIE JI Nephrologie PY 1996 VL 17 IS 8 BP 457 EP 461 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA WB133 UT WOS:A1996WB13300008 PM 9036371 ER PT J AU Striker, GE Eastman, RD Striker, LJ AF Striker, GE Eastman, RD Striker, LJ TI Diabetic nephropathy: Molecular analysis of extracellular matrix and clinical studies update SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE diabetes mellitus; extracellular matrix; glomerulosclerosis; molecular analysis ID BOVINE GROWTH-HORMONE; TRANSGENIC MICE; GENE-EXPRESSION; MESSENGER-RNAS; MELLITUS; GLOMERULI; GLOMERULOSCLEROSIS; COLLAGEN; INSULIN; RATS AB Background Progressive glomerulosclerosis associated with decreasing kidney function, resulting in end-stage renal failure, is the major finding in diabetic nephropathy. There are multiple components of the extracellular matrix, and neither the exact composition nor the factors responsible for its increase in diabetic nephropathy is known. Methods. We examined matrix synthesis and degradation at the level of gene expression and ECM composition, in the glomeruli of diabetic mice transgenic for a mutated bGH and their littermate controls, and in renal biopsies of patients with diabetic nephropathy. Results. found that streptozotocin-treated C57BL/SJL mice developed histological lesions closely resembling human diabetic glomerulosclerosis, whereas there were no glomerular lesions in diabetic mice transgenic for a growth hormone analogue which competes with native GH and results in dwarfism. We found that diabetic glomerulosclerosis in mice was associated with an increase in type IV collagen and laminin synthesis, and that these changes are selectively inhibited in dwarf mice transgenic for the mutant GH analogue. Preliminary examination of glomeruli isolated from renal biopsies revealed a homogeneous elevation in the alpha 2/alpha 3IV ratio among diabetics. Conclusions. These data suggested that diabetic nephropathy is characterized by modifications in ECM gene regulation in both mouse models and in diabetics, and that GH may promote the susceptibility to this complication. Finally, the data from the Diabetes Control and Complications Trial is updated, emphasizing the importance of close glucose control in the amelioration of an elevated albumin excretion rate as a continuous function of the level of control. C1 NIDDKD,DIV DIABET ENDOCRINOL & METAB DIS,NIH,BETHESDA,MD 20892. NIH,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. RP Striker, GE (reprint author), NIDDKD,DIV KIDNEY UROL & HEMATOL DIS,NIH,BETHESDA,MD 20892, USA. NR 31 TC 12 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PY 1996 VL 11 SU 5 BP 58 EP 61 PG 4 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA WH973 UT WOS:A1996WH97300013 PM 9044309 ER PT J AU Striker, LJ Striker, GE AF Striker, LJ Striker, GE TI Administration of AGEs in vivo induces extracellular matrix gene expression SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE advanced glycosylation end-products; extracellular matrix; glomeruli ID ADVANCED GLYCOSYLATION; DIABETIC RATS; END-PRODUCTS; COLLAGEN AB The role that advanced glycosylation end-products (AGEs) may play in the development of diabetic nephropathy is still not completely understood. In order to elucidate the nature of their effect, the consequences of exogenously administered AGEs on extracellular matrix gene expression were examined in mice by competitive PCR. Normal adult mice receiving repeated injections of AGEs had an increase in the expression of genes coding for type IV collagen and laminin in the glomeruli. The increase was accompanied by up-regulation of TGF-beta 1 but not PDGF-B expression. The expression of smooth muscle and beta-actin did not change, showing that the increase in gene expression was specific for genes implicated in the early stages of diabetic nephropathy. The co-administration of aminoguanidine, a drug that inhibits AGEs cross-links, prevented the up-regulation of gene expression in AGEs-injected mice. Thus, AGEs can induce extracellular matrix genes in the absence of hyperglycaemia. C1 NIH,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. NR 11 TC 23 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PY 1996 VL 11 SU 5 BP 62 EP 65 PG 4 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA WH973 UT WOS:A1996WH97300014 PM 9044310 ER PT J AU Softky, WR AF Softky, WR TI Fine analog coding minimizes information transmission SO NEURAL NETWORKS LA English DT Article DE information; infomax; analog; binary; coding; noise; signal-to-noise; coarse coding ID NEURAL NETWORK; SPIKE TRAINS; POTENTIALS; DENDRITES; NEURONS; CELLS AB One measure of the computational power of a single unit in a network is the rate at which ii can transfer information. Because that rate depends both on the unit's analog resolution and on its speed, many types of units may reach their optimum information flow when they operate very fast, with only coarse or binary resolution at each time step (this occurs because the information rate scales linearly with speed or bandwidth, but only logarithmically with analog resolution). Furthermore, calculations for a mean-square-limited channel with Gaussian noise show that the optimum information rate for the best possible analog code ir only about 30% better than the optimum rate for the simplest binary code. For the biologically realistic case of an irregular neural spike train, a binary code carries about two orders of magnitude more information than an analog rate-code using the same spikes, and is equally consistent with neurophysiology. Thus, neural networks that optimally transfer information would probably use a binary (or coarse analog) code, rather than the high-resolution, real-valued codes usually explored. RP Softky, WR (reprint author), NIDDK,MATH RES BRANCH,NIH,9190 WISCONSIN AVE,SUITE 350,BETHESDA,MD 20892, USA. NR 30 TC 15 Z9 15 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD JAN PY 1996 VL 9 IS 1 BP 15 EP 24 DI 10.1016/0893-6080(95)00012-7 PG 10 WC Computer Science, Artificial Intelligence SC Computer Science GA TX666 UT WOS:A1996TX66600004 ER PT S AU Grady, CL AF Grady, CL BE Wurtman, RJ Corkin, S Growdon, JH Nitsch, RM TI Age-related changes in cortical blood flow activation during perception and memory SO NEUROBIOLOGY OF ALZHEIMER'S DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th Meeting of the International-Study-Group-on-the-Pharmacology-of-Memory-Disorders-Associ ated-with-Aging on the Neurobiology of Alzheimers Disease CY FEB 17-19, 1995 CL ZURICH, SWITZERLAND SP Int Study Grp Pharm Memory Disorders Associated Aging, Ctr Brain Sci & Metabolism Charitable Trust, Cambridge Massachusetts, Alzheimers Assoc, French Fdn, Helen Bader Fdn, John D & Catherine T MacArthur Fdn ID HUMAN-BRAIN; CORTEX AB Although many cognitive functions are affected by age, some are relatively maintained. There also are numerous age-related changes in brain structure, but not much is known about how these changes impact upon the alterations seen in cognition. In order to understand the basis for the reductions and sparings of cognitive function in the aged, experiments were carried out to compare regional cerebral blood flow (rCBP) and performance in young and old subjects on visual perceptual and memory tasks. In the first experiment, which examined the perception of faces and spatial locations, old subjects were as accurate as young subjects, and both groups had rCBF activation in fusiform gyrus during face matching and in superior parietal cortex during location matching. However, old subjects had less activation of prestriate cortex and more activation of frontal and lateral temporal cortex than did young subjects. The second experiment tested recognition memory for faces, a task on which old subjects were impaired. Young subjects had rCBF activation in left prefrontal and inferior temporal cortex and in right hippocampus during encoding of the faces, and in right prefrontal and parietal cortex during recognition. Old subjects showed no significant activation of the areas involved in encoding, but did have increased rCBF in right prefrontal cortex during recognition. These results suggest that the aging brain can demonstrate alterations of the functional systems involved in some cognitive processes, such as perception, that may serve as a compensatory mechanism to maintain performance. Failure to show such compensation, coupled with dysfunction of the areas primarily involved in processing may lead to more marked deficits in performance. RP Grady, CL (reprint author), NIA,NEUROSCI LAB,NIH,10-6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 18 TC 36 Z9 37 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-974-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 777 BP 14 EP 21 DI 10.1111/j.1749-6632.1996.tb34396.x PG 8 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BF30Z UT WOS:A1996BF30Z00002 PM 8624077 ER PT S AU Wolozin, BL BasaricKeys, J Canter, R Li, Y Vanderputten, D Sunderland, T AF Wolozin, BL BasaricKeys, J Canter, R Li, Y Vanderputten, D Sunderland, T BE Wurtman, RJ Corkin, S Growdon, JH Nitsch, RM TI Differential regulation of APP secretion by apolipoprotein E3 and E4 SO NEUROBIOLOGY OF ALZHEIMER'S DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th Meeting of the International-Study-Group-on-the-Pharmacology-of-Memory-Disorders-Associ ated-with-Aging on the Neurobiology of Alzheimers Disease CY FEB 17-19, 1995 CL ZURICH, SWITZERLAND SP Int Study Grp Pharm Memory Disorders Associated Aging, Ctr Brain Sci & Metabolism Charitable Trust, Cambridge Massachusetts, Alzheimers Assoc, French Fdn, Helen Bader Fdn, John D & Catherine T MacArthur Fdn ID ONSET ALZHEIMER-DISEASE; AMYLOID-BETA-PEPTIDE; TYPE-4 ALLELE; BINDING AB The apolipoprotein E isozyme, apolipoprotein E4, has been implicated as a risk factor for Alzheimer's disease. One reason for the increased risk may be that apolipoprotein E binds to the AP peptide, but there may be other factors as well. We show that apolipoprotein E is a potent regulator of the secretion of amyloid precursor protein. In cultures of PC12 cells, nanomolar levels of apolipoprotein E3 induce a rapid decrease in the secretion of APP, being observable in 30 min. and stable over 24 hours. Apolipoprotein E4, in contrast, increases secretion of APP over a similar time course. Reciprocal changes occur in cellular amyloid precursor protein. Differential characteristics are also seen in apo E binding to the cells, where apo E4 binds over a slower time course than apo E3. These results suggest a novel mechanism by which apolipoprotein E may be influencing the metabolism of amyloid precursor protein. C1 NIMH,LAB BIOCHEM GENET,BETHESDA,MD 20892. RP Wolozin, BL (reprint author), NIMH,SECT GERIATR PSYCHIAT,BLDG 10,RM 3D41,10 CTR DR,MSC 1264,BETHESDA,MD 20892, USA. NR 7 TC 12 Z9 12 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-974-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 777 BP 322 EP 326 DI 10.1111/j.1749-6632.1996.tb34440.x PG 5 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BF30Z UT WOS:A1996BF30Z00046 PM 8624107 ER PT S AU Mason, RP Trumbore, MW Pettegrew, JW AF Mason, RP Trumbore, MW Pettegrew, JW BE Wurtman, RJ Corkin, S Growdon, JH Nitsch, RM TI Molecular membrane interactions of a phospholipid metabolite - Implications for Alzheimer's disease pathophysiology SO NEUROBIOLOGY OF ALZHEIMER'S DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 8th Meeting of the International-Study-Group-on-the-Pharmacology-of-Memory-Disorders-Associ ated-with-Aging on the Neurobiology of Alzheimers Disease CY FEB 17-19, 1995 CL ZURICH, SWITZERLAND SP Int Study Grp Pharm Memory Disorders Associated Aging, Ctr Brain Sci & Metabolism Charitable Trust, Cambridge Massachusetts, Alzheimers Assoc, French Fdn, Helen Bader Fdn, John D & Catherine T MacArthur Fdn ID BRAIN AB Alzheimers's disease is characterized by changes in phospholipid metabolism leading to a perturbation in the levels of phosphomonoesters, including L-Phosphoserine (L-PS). These early changes in lipid metabolism may result in a defect in membrane bilayer structure, leading to increased rates of beta-amyloid formation. To investigate the effect of L-PS on membrane lipid bilayers, small angle x-ray diffraction and high resolution differential scanning calorimetry (DSC) approaches were used with liposomes composed of lecithin and cholesterol. A one-dimensional electron density profile of a control dimyristoyl phosphatidylcholine (DMPC)/cholesterol lipid bilayer with a unit cell dimension of 52 Angstrom at 37 degrees C was generated from the x-ray diffraction data. Following incubation with 2.0 mM L-PS, a broad decrease in electron density +/-4-12 Angstrom from the lipid bilayer center was observed concomitant with an increase in the width of the phospholipid headgroup electron density and a 3 Angstrom reduction in lipid bilayer width. The interactions of L-PS with DMPC lipid bilayers were concentration-dependent, highly affected by cholesterol content and reproduced in egg phosphatidylcholine/cholesterol liposomes. DSC analysis showed that millimolar (1.0-5.0 mM) L-PS levels decreased the phase transition cooperative unit size of DMPC liposomes in a highly concentration-dependent manner which was significantly greater in preparations containing 10 mol% cholesterol. These data provide direct evidence that phosphomonoester levels modulate the biophysical properties of the membrane lipid bilayer which may, in turn, lead to altered structure/function relationships in AD. C1 NCI,NIH,BETHESDA,MD 20892. UNIV PITTSBURGH,LAB NEUROPHYS,PITTSBURGH,PA. RP Mason, RP (reprint author), MED COLL PENN & HAHNEMANN UNIV,NEUROSCI RES CTR,320 E NORTH AVE,ALLEGHENY CAMPUS,PITTSBURGH,PA 15212, USA. FU NIA NIH HHS [AG05133, AG08371, AG08974] NR 10 TC 8 Z9 8 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-974-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 777 BP 368 EP 373 DI 10.1111/j.1749-6632.1996.tb34447.x PG 6 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BF30Z UT WOS:A1996BF30Z00053 PM 8624114 ER PT B AU Bing, GY Wilson, B McMillian, M Feng, ZH Qi, QP Kim, HC Wang, W Jensen, K Hong, JS AF Bing, GY Wilson, B McMillian, M Feng, ZH Qi, QP Kim, HC Wang, W Jensen, K Hong, JS BE Fiskum, G TI Long-term expression of proenkephalin and prodynorphin in the rat brain after systemic administration of kainic acid - An in situ hybridization study SO NEURODEGENERATIVE DISEASES: MOLECULAR AND CELLULAR MECHANISMS AND THERAPEUTIC ADVANCES SE GWUMC DEPARTMENT OF BIOCHEMISTRY ANNUAL SPRING SYMPOSIA LA English DT Proceedings Paper CT 15th Washington International Spring Symposium on Health Science - Neurodegenerative Diseases: Molecular and Cellular Mechanisms and Therapeutic Advances CY MAY 15-17, 1995 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC HO GEORGE WASHINGTON UNIV C1 NIEHS,NIH,LAB ENVIRONM NEUROSCI,RES TRIANGLE PK,NC 27709. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45298-7 J9 GWUMC DEPT PY 1996 BP 9 EP 18 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BF46Q UT WOS:A1996BF46Q00002 ER PT B AU Wolozin, B BasaricKeys, J Canter, R Li, YH Strickland, D Sunderland, T AF Wolozin, B BasaricKeys, J Canter, R Li, YH Strickland, D Sunderland, T BE Fiskum, G TI Differential regulation of APP secretion by apolipoprotein E3 and E4 SO NEURODEGENERATIVE DISEASES: MOLECULAR AND CELLULAR MECHANISMS AND THERAPEUTIC ADVANCES SE GWUMC DEPARTMENT OF BIOCHEMISTRY ANNUAL SPRING SYMPOSIA LA English DT Proceedings Paper CT 15th Washington International Spring Symposium on Health Science - Neurodegenerative Diseases: Molecular and Cellular Mechanisms and Therapeutic Advances CY MAY 15-17, 1995 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC HO GEORGE WASHINGTON UNIV C1 NIMH,SECT GERIATR PSYCHIAT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45298-7 J9 GWUMC DEPT PY 1996 BP 97 EP 102 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BF46Q UT WOS:A1996BF46Q00014 ER PT B AU Sokoloff, L Takahashi, S AF Sokoloff, L Takahashi, S BE Fiskum, G TI Functional activation of energy metabolism in nervous tissue: Where and why SO NEURODEGENERATIVE DISEASES: MOLECULAR AND CELLULAR MECHANISMS AND THERAPEUTIC ADVANCES SE GWUMC DEPARTMENT OF BIOCHEMISTRY ANNUAL SPRING SYMPOSIA LA English DT Proceedings Paper CT 15th Washington International Spring Symposium on Health Science - Neurodegenerative Diseases: Molecular and Cellular Mechanisms and Therapeutic Advances CY MAY 15-17, 1995 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC HO GEORGE WASHINGTON UNIV C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45298-7 J9 GWUMC DEPT PY 1996 BP 147 EP 169 PG 23 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BF46Q UT WOS:A1996BF46Q00021 ER PT B AU Merril, CR Zullo, S Ghanbari, H AF Merril, CR Zullo, S Ghanbari, H BE Fiskum, G TI Is there a relationship between conditions associated with chronic hypoxia, the mitochondria, and neurodegenerative diseases, such as Alzheimer's disease? SO NEURODEGENERATIVE DISEASES: MOLECULAR AND CELLULAR MECHANISMS AND THERAPEUTIC ADVANCES SE GWUMC DEPARTMENT OF BIOCHEMISTRY ANNUAL SPRING SYMPOSIA LA English DT Proceedings Paper CT 15th Washington International Spring Symposium on Health Science - Neurodegenerative Diseases: Molecular and Cellular Mechanisms and Therapeutic Advances CY MAY 15-17, 1995 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC HO GEORGE WASHINGTON UNIV C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,LAB BIOCHEM GENET,NIH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45298-7 J9 GWUMC DEPT PY 1996 BP 181 EP 184 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BF46Q UT WOS:A1996BF46Q00023 ER PT B AU Harris, HW AF Harris, HW BE Fiskum, G TI Neuronal differentiation of PC12 cells in the absence of extracellular matrix adhesion induces apoptosis SO NEURODEGENERATIVE DISEASES: MOLECULAR AND CELLULAR MECHANISMS AND THERAPEUTIC ADVANCES SE GWUMC DEPARTMENT OF BIOCHEMISTRY ANNUAL SPRING SYMPOSIA LA English DT Proceedings Paper CT 15th Washington International Spring Symposium on Health Science - Neurodegenerative Diseases: Molecular and Cellular Mechanisms and Therapeutic Advances CY MAY 15-17, 1995 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC HO GEORGE WASHINGTON UNIV C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45298-7 J9 GWUMC DEPT PY 1996 BP 405 EP 407 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BF46Q UT WOS:A1996BF46Q00049 ER PT J AU Quan, N Zhang, ZB Emery, M Bonsall, R Weiss, JM AF Quan, N Zhang, ZB Emery, M Bonsall, R Weiss, JM TI Detection of interleukin-1 bioactivity in various brain regions of normal healthy rats SO NEUROIMMUNOMODULATION LA English DT Article DE interleukin-1; bioactivity; brain; cytokine; D10 cell assay ID CORTICOTROPIN-RELEASING FACTOR; TUMOR-NECROSIS-FACTOR; MESSENGER-RNA; IMMUNOREACTIVE INTERLEUKIN-1-BETA; CEREBROSPINAL-FLUID; ALPHA-MSH; IN-VITRO; INDUCTION; LIPOPOLYSACCHARIDE; SLEEP AB Although interleukin-1 (IL-1) has been implicated in an array of brain functions, past studies usually have failed to detect IL-1 bioactivity in the brain of normal healthy animals. However, in view of the potency of IL-1 in brain, small amounts of this cytokine may normally act in brain, and such quantities can escape detection by assay methods usually employed. Although bioassays are highly sensitive for detecting IL-1, these can be compromised by molecules in brain tissue other than IL-1, and attempts to purify IL-1 from brain tissue can result in significant loss of IL-1 from samples. In this study, we have refined our method of assessing brain IL-1 bioactivity by first semi-isolating IL-1 with a Sephadex minicolumn and then measuring IL-1 activity with a sensitive D10 cell assay. To confirm that our assay was specific for IL-1, a monoclonal antibody against IL-1 receptor was used to block any observed IL-1 activity. We report here that IL-1 bioactivity can be reliably detected in both the cell-free supernatant and cell lysate of brainstem, cortex, diencephalon, and hippocampus of normal rat brain. These results lend support to some recent studies that found IL-1 may play important roles in the functions of normal brain. C1 GEORGIA MENTAL HLTH INST,ATLANTA,GA 30306. EMORY UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,ATLANTA,GA 30322. NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. FU NIMH NIH HHS [MH-50420] NR 34 TC 37 Z9 40 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD JAN-FEB PY 1996 VL 3 IS 1 BP 47 EP 55 DI 10.1159/000097226 PG 9 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA VJ393 UT WOS:A1996VJ39300004 PM 8892360 ER PT J AU Quan, N Zhang, ZB Emery, M Lai, E Bonsall, R Kalyanaraman, VS Weiss, JM AF Quan, N Zhang, ZB Emery, M Lai, E Bonsall, R Kalyanaraman, VS Weiss, JM TI In vivo induction of interleukin-1 bioactivity in brain tissue after intracerebral infusion of native gp120 and gp160 SO NEUROIMMUNOMODULATION LA English DT Article DE interleukin-1; gp120, native; gp160, native; brain; bioactivity ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; CORTICOTROPIN-RELEASING FACTOR; CELLULAR IMMUNE-RESPONSES; CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; ENVELOPE PROTEIN; HIV-INFECTION; FACTOR-ALPHA; GLIAL-CELLS AB We have previously reported that intracerebral infusion of recombinant human immunodeficiency virus envelope protein gp120 induced interleukin-1 (IL-1) bioactivity in rat brain. In this study, we tested the ability of native gp120 and gp160 to induce IL-1 activity in rat brain and also examined whether altering the secondary and tertiary structures of these proteins by carboxymethylation could influence the IL-1-inducing effect of these peptides, Results showed that both native gp120 and gp160 can induce IL-1 activity in rat brain in vivo, and that intact secondary and tertiary structures of these proteins appear critical for this effect. C1 GEORGIA MENTAL HLTH INST, ATLANTA, GA 30306 USA. EMORY UNIV, SCH MED, DEPT PSYCHIAT & BEHAV SCI, ATLANTA, GA 30322 USA. NIMH, FUNCT NEUROANAT SECT, BETHESDA, MD 20892 USA. ADV BIOSCI LABS, KENSINGTON, MD USA. FU NIMH NIH HHS [MH-50420] NR 35 TC 12 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD JAN-FEB PY 1996 VL 3 IS 1 BP 56 EP 61 DI 10.1159/000097227 PG 6 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA VJ393 UT WOS:A1996VJ39300005 PM 8892361 ER PT J AU Higgins, JJ Nee, LE Vasconcelos, O Ide, SE Lavedan, C Goldfarb, LG Polymeropoulos, MH AF Higgins, JJ Nee, LE Vasconcelos, O Ide, SE Lavedan, C Goldfarb, LG Polymeropoulos, MH TI Mutations in American families with spinocerebellar ataxia (SCA) type 3: SCA3 is allelic to Machado-Joseph disease SO NEUROLOGY LA English DT Article ID HUNTINGTONS-DISEASE; DEGENERATION; EXPANSION; REPEAT AB We identified an expansion of the CAG trinucleotide repeat in the coding region of the Machado-Joseph disease gene in 7 of 24 American families diagnosed with autosomal dominant ataxia. All affected individuals were heterozygous for an expanded allele that ranged from 67 to more than 200 CAG repeats, whereas the normal allele had 14 to 33 repeats. In contrast to the Azorean-Portuguese origins of Machado-Joseph disease, the two largest American families were of German and Dutch-African descent. Clinical, pathologic, and genetic evaluations suggest that American families with spinocerebellar ataxia type 3 differ from those with Machado-Joseph disease by their ethnic origins, predominant spinopontine atrophy, lack of dystonic features, and larger CAG repeat expansion. C1 NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892. RP Higgins, JJ (reprint author), NINCDS,CLIN NEUROGENET UNIT,MED NEUROL BRANCH,ROOM 5N234,BETHESDA,MD 20892, USA. NR 28 TC 51 Z9 52 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 1996 VL 46 IS 1 BP 208 EP 213 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA TR671 UT WOS:A1996TR67100042 PM 8559377 ER PT S AU Donovan, DM Miner, LL Sharpe, L Cho, HJ Takemura, M Unterwald, E Nyberg, F Kreek, MJ Uhl, GR AF Donovan, DM Miner, LL Sharpe, L Cho, HJ Takemura, M Unterwald, E Nyberg, F Kreek, MJ Uhl, GR BE Crawley, JN McLean, S TI Transgenic mice: Preproenkephalin and the mu opiate receptor SO NEUROPEPTIDES: BASIC AND CLINICAL ADVANCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 1995 Summer Neuropeptide Conference CY JUN 25-29, 1995 CL MARTHAS VINEYARD, MA SP Int Neuropeptide Soc, Amgen Inc, Bachem Biosci Inc, Bristol Myers Squibb Co, Burroughs Wellcome Co, Cephalon Inc, Council Tobacco Res US Inc, Dupont Merck Pharm Co, Int Soc Neurochem, Eli Lilly & Co, Lilly Res Labs, Marion Merrell Dow Res Inst, Merck Sharp & Dohme Res Labs, NIDA, Warner Lambert Co, Parke Davis Pharm Res, Pfizer Inc, Pfizer Cent Res, Wyeth Ayerst Res ID MESSENGER-RNA; PROENKEPHALIN GENE; CDNA CLONING; CYCLIC AMP; EXPRESSION; ENKEPHALIN; STIMULATION; DYNORPHIN; ELEMENT; NEURONS C1 KYUNG POOK NATL UNIV, SCH MED, DEPT ANAT, KTAEGU, SOUTH KOREA. OSAKA UNIV, FAC DENT, DEPT ANAT, SUITA, OSAKA 565, JAPAN. ROCKEFELLER UNIV, BIOL ADDICT DIS LAB, NEW YORK, NY 10021 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21224 USA. UNIV UPPSALA, DEPT PHARMACOL, S-75124 UPPSALA, SWEDEN. RP Donovan, DM (reprint author), NIDA, MOL NEUROBIOL BRANCH, DIV INTRAMURAL RES, NIH, POB 5180, BALTIMORE, MD 21224 USA. NR 25 TC 1 Z9 1 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 0-89766-990-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 780 BP 19 EP 28 DI 10.1111/j.1749-6632.1996.tb15108.x PG 10 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BF66U UT WOS:A1996BF66U00002 PM 8602733 ER PT S AU Schwartz, JP Taniwaki, T Messing, A Brenner, M AF Schwartz, JP Taniwaki, T Messing, A Brenner, M BE Crawley, JN McLean, S TI Somatostatin as a trophic factor - Analysis of transgenic mice overexpressing somatostatin in astrocytes SO NEUROPEPTIDES: BASIC AND CLINICAL ADVANCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1995 Summer Neuropeptide Conference CY JUN 25-29, 1995 CL MARTHAS VINEYARD, MA SP Int Neuropeptide Soc, Amgen Inc, Bachem Biosci Inc, Bristol Myers Squibb Co, Burroughs Wellcome Co, Cephalon Inc, Council Tobacco Res US Inc, Dupont Merck Pharm Co, Int Soc Neurochem, Eli Lilly & Co, Lilly Res Labs, Marion Merrell Dow Res Inst, Merck Sharp & Dohme Res Labs, NIDA, Warner Lambert Co, Parke Davis Pharm Res, Pfizer Inc, Pfizer Cent Res, Wyeth Ayerst Res ID INFLUENCE NEURONAL EXPRESSION; HORMONE-RELEASING HORMONE; DEVELOPING CHICK BRAIN; TRANSIENT EXPRESSION; RAT CEREBELLUM; MESSENGER-RNA; SMS 201-995; GROWTH; INHIBITION; ANALOG C1 NINCDS,NIH,STROKE BRANCH,BETHESDA,MD 20892. UNIV WISCONSIN,SCH VET MED,DEPT PATHOBIOL SCI,MADISON,WI 53706. RP Schwartz, JP (reprint author), NINCDS,NIH,CLIN NEUROSCI BRANCH,MOLEC GENET SECT,BLDG 10,ROOM 3N256,BETHESDA,MD 20892, USA. NR 28 TC 9 Z9 9 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 SN 0077-8923 BN 0-89766-990-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1996 VL 780 BP 29 EP 35 DI 10.1111/j.1749-6632.1996.tb15109.x PG 7 WC Multidisciplinary Sciences; Neurosciences SC Science & Technology - Other Topics; Neurosciences & Neurology GA BF66U UT WOS:A1996BF66U00003 PM 8602737 ER PT J AU Gunnersen, D Kaufman, CM Skolnick, P AF Gunnersen, D Kaufman, CM Skolnick, P TI Pharmacological properties of recombinant ''diazepam-insensitive'' GABA(A) receptors SO NEUROPHARMACOLOGY LA English DT Article DE GABA(A) receptor; imidazobenzodiazepine; benzodiazepine; Ro 15-4513; diazepam-insensitive; recombinant receptors ID GAMMA-AMINOBUTYRIC-ACID; CEREBELLAR GRANULE CELLS; H-3 RO 15-4513; BENZODIAZEPINE RECEPTORS; A RECEPTORS; SUBUNIT COMPOSITION; ALCOHOL ANTAGONIST; ALPHA-SUBUNIT; SINGLE HISTIDINE; RO 15-4513 AB Both native and recombinant ''diazepam-insensitive'' GABA(A) receptors (DI) are characterized by the very low affinities of prototypic 1,4-benzodiazepines such as diazepam and the high affinity of an imidazobenzodiazepine, Ro 15-4513. The presence of either an alpha(4) or alpha(6) subunit imparts this unusual pharmacological profile to DI. Based on the affinities of these compounds at recombinant DI, the pharmacological properties of alpha(4)- and alpha(6)-bearing receptor isoforms appear to be very similar if not identical. Using a larger sample of structurally diverse compounds, we now demonstrate distinct but related ligand binding profiles of recombinant alpha(4) beta(2) gamma(2) and alpha(6) beta(2) gamma(2) DI. Comparison of 18 ligands drawn from three principal structural groups (beta-carbolines, imidazobenzodiazepines and pyrazoloquinolinones) revealed that the affinity of at least one representative from each group differed by >5-fold between alpha(4)- and alpha(6) beta(2) gamma(2) receptors. While the high correlation (r(2) = 0.926; p < 0.001) obtained between the affinities of these ligands at alpha(4)- and alpha(6)-containing receptors underscores the similarity between these receptor isoforms, a significant deviation of the slope of this correlation (0.792; 95% C.I. 0.673-0.911) from unity is substantive evidence that these DI possess distinct pharmacological profiles. These findings indicate that it is feasible to develop selective ligands for these DI isoforms. Published by Elsevier Science Ltd. RP Gunnersen, D (reprint author), NIDDK,NIH,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 43 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PY 1996 VL 35 IS 9-10 BP 1307 EP 1314 DI 10.1016/S0028-3908(96)00054-8 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA WC182 UT WOS:A1996WC18200019 PM 9014146 ER PT J AU Mapou, RL Law, WA Heyes, MP Turnicky, R Ling, GSF Dopler, B Martin, A Brown, D Temoshok, LR AF Mapou, RL Law, WA Heyes, MP Turnicky, R Ling, GSF Dopler, B Martin, A Brown, D Temoshok, LR TI Relationships among cerebrospinal fluid human immunodeficiency virus type 1 (HIV-1) culture, quinolinic acid level, and reaction time in HIV-1-infected individuals SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID L-TRYPTOPHAN; INFECTION; BRAIN; AIDS; ABNORMALITIES; BLOOD; DEFICIENCY; DEMENTIA; ANTIGEN; SERUM AB This study examined the relationships among cerebrospinal fluid (CSF) HIV-1 culture, quinolinic acid (QUIN) levels, and neurobehavioral functioning as measured by reaction time (RT) in HIV-1-infected (HIV+) individuals. Twenty HIV+ subjects completed lumbar puncture, neurological screening, magnetic resonance imaging scan, RT procedures, an estimated IQ measure, and self-reported mood state measures. Routine CSF laboratory studies, including white blood cell count (WBC), red blood cell count, protein, glucose; and percentage IgG were conducted. CSF was cultured for HIV-1 and assayed for QUIN. Subjects with positive HIV-1 CSF culture (CSF+) had significantly higher QUIN levels than subjects with negative HIV-1 CSF culture (CSF-), although this difference was attenuated when WBC was controlled. Controlling for age and education, MANCOVA showed that CSF+ subjects had significantly slower RTs than CSF- subjects. Controlling for WBC did not change RT findings. Logistic regression indicated that both RT and QUIN contributed to the prediction of culture group. Group differences could not be explained by demographic factors, history, neurologic status, or medical status. Findings suggest a link among ability to culture HIV-1 from CSF, elevated QUIN, and slowed RT. This link, in turn, suggests a potential HIV-1-specific biological marker associated with neurobehavioral change in HIV-1 disease. Findings may be related to subclinical brain inflammation. C1 MIL MED CONSORTIUM APPL RETROVIRAL RES,ROCKVILLE,MD 20850. WALTER REED ARMY INST RES,ROCKVILLE,MD. NIMH,WASHINGTON,DC. WALTER REED ARMY MED CTR,WASHINGTON,DC. RP Mapou, RL (reprint author), HENRY M JACKSON FDN ADVANCEMENT MIL MED,1 TAFT COURT,SUITE 250,ROCKVILLE,MD 20850, USA. RI martin, alex/B-6176-2009 NR 36 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JAN PY 1996 VL 9 IS 1 BP 43 EP 49 PG 7 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA TN508 UT WOS:A1996TN50800006 ER PT J AU Schulz, H Jobert, M Coppola, R Herrmann, WM Pantev, M AF Schulz, H Jobert, M Coppola, R Herrmann, WM Pantev, M TI The use of diurnal vigilance changes in the EEG to verify vigilance-enhancing effects of memantine in a clinical pharmacological study SO NEUROPSYCHOBIOLOGY LA English DT Article DE memantine; pharmaco-EEG; EEG mapping; descriptive data analysis; distance computation; vigilance model ID MAPS AB In elderly subjects there is a vigilance decrease from morning to noon which was used in a clinical pharmacological model as a state condition to verify vigilance-enhancing effects of an antidementia drug. In this model the effects of Memantine (20 mg, single-dose application) on the quantified EEG were investigated in 16 elderly (mean age: 65 +/- 5 years), healthy subjects (10 females, 6 males) in a randomised, twofold cross-over design vs. placebo under double-blind conditions. EEG was recorded before medication, and 2 and 4 h after medication under reaction time (RT) and resting (RS) conditions. EEG data were subjected to spectral analysis and the topographic distribution of the amplitude values was mapped. The results show that a time-dependent decrease (from morning to noon) in vigilance (indicated by an increase in average EEG amplitudes caused by increased synchronisation in the alpha and beta range and an increase in delta) occurred under placebo which was counteracted by Memantine. The diurnal variations of the EEG and their compensation by a pharmacological agent represent an effective model for investigating the vigilance-enhancing effects of antidementia drugs. C1 PAREXEL INDEPENDENT PHARMACEUT RES ORG GMBH,KLINIKUM WESTEND,D-14050 BERLIN,GERMANY. FREE UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,DEPT PSYCHIAT,LAB CLIN PSYCHOPHYSIOL,W-1000 BERLIN,GERMANY. MERZ & CO PHARMA,CLIN CNS RES,FRANKFURT,GERMANY. NIMH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. NR 33 TC 23 Z9 24 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 1996 VL 33 IS 1 BP 32 EP 40 DI 10.1159/000119246 PG 9 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA TT262 UT WOS:A1996TT26200006 PM 8821373 ER PT J AU Gold, JM Berman, KF Randolph, C Goldberg, TE Weinberger, DR AF Gold, JM Berman, KF Randolph, C Goldberg, TE Weinberger, DR TI PET validation of a novel prefrontal task: Delayed response alternation SO NEUROPSYCHOLOGY LA English DT Article ID WORKING-MEMORY; FRONTAL-CORTEX; DISSOCIATION; PERFORMANCE; HUMANS; OBJECT AB Deficits in working memory have been proposed to explain the performance failures of frontally lesioned primates on delayed alternation(DA) and delayed response (DR) tasks. The authors examined a computerized test of delayed response alternation (DRA), which combines elements of DR and DA in a sample of 18 normal volunteers who underwent oxygen-15 PET regional cerebral blood flow scans during the DRA and a sensorimotor control task. Significant activations were observed in a network of frontal, parietal, occipital, and temporal regions during initial task performance. A qualitatively similar but somewhat reduced set of activations was observed in a subset of participants who repeated the task after practice and instruction. These results are consistent with distributed models of working memory derived from studies of nonhuman primates and suggest that the frontal lobes contribute to human working memory function. C1 ST ELIZABETH HOSP, NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. NR 32 TC 64 Z9 67 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 1996 VL 10 IS 1 BP 3 EP 10 PG 8 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA TN430 UT WOS:A1996TN43000001 ER PT J AU Ingraham, LJ Aiken, CB AF Ingraham, LJ Aiken, CB TI An empirical approach to determining criteria for abnormality in test batteries with multiple measures SO NEUROPSYCHOLOGY LA English DT Article ID COMPLEX AB Investigators and clinicians are sometimes confronted with the task of determining whether a pattern of scores on a variety of measures reflects impairment. As the number of measures increases, so does the probability that scores on some of the measures will be in the abnormal range. A simple method for setting an overall criterion for abnormality when using multiple measures is presented, and an approach for setting criteria when some of the measures are correlated is suggested. The approach is applied to a study of the neuropsychological manifestations of HIV-1 infection, and the model is found to agree with observed results. RP Ingraham, LJ (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BLDG 10,ROOM 4C110,BETHESDA,MD 20892, USA. NR 10 TC 118 Z9 119 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 1996 VL 10 IS 1 BP 120 EP 124 DI 10.1037/0894-4105.10.1.120 PG 5 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA TN430 UT WOS:A1996TN43000014 ER PT J AU Higley, JD King, ST Hasert, MF Champoux, M Suomi, SJ Linnoila, M AF Higley, JD King, ST Hasert, MF Champoux, M Suomi, SJ Linnoila, M TI Stability of interindividual differences in serotonin function and its relationship to severe aggression and competent social behavior in rhesus macaque females SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin; 5-Hydroxyindoleacetic acid; aggression; stress; primate; social competence ID CEREBROSPINAL-FLUID MONOAMINE; MONKEYS MACACA-MULATTA; MALE VERVET MONKEYS; 5-HYDROXYINDOLEACETIC ACID; ELECTROCHEMICAL DETECTION; AMINE METABOLITES; HOMOVANILLIC-ACID; STRESS; BRAIN; FENFLURAMINE AB Few studies have investigated longitudinally interindividual stability of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations in adult nonhuman primates across time and between baseline and stressful conditions. Furthermore, whereas studies with male macaques consistently have reported a significant, negative correlation between CSF 5-HIAA and rates of spontaneous aggression, wounding, and severe aggression, very few studies have examined this relationship in adult female nonhuman primates. Even fewer studies have investigated correlations between CSF 5-HIAA and competent social behavior, such as social dominance, in female monkeys. In the present study, two social groups of adult rhesus monkeys (Macaca mulatta) were formed by placing 16 females (aged 42 to 180 months, mean age: 68 months) in one of two indoor-outdoor enclosures with one or two adult males. CSF norepinephrine (NE), monoamine metabolites, and behavioral data were collected systematically over a 24-week period. In week 5 of the study, one additional female, not familiar to any of the other subjects, was added to each social group. Thereafter the groups were left undisturbed, and data characterizing spontaneous aggressive wounding and severe wound injuries in the females were collected for an additional year The results showed that both group introduction and the addition of a new subject into each group resulted in increased monoamine turnover in the animals within the social groups. Interindividual differences in CSF concentrations of each of the monoamine metabolites and NE were highly stable from the baseline period to the stress samplings, and between stress samplings. Females with low CSF 5-HIAA exhibited higher rates of spontaneous aggressive wounding, and they were more likely to be removed from their social groups for aggressive wounding and/or treatment of injuries. CSF NE concentrations also were negatively correlated with rates of spontaneous aggression. In contrast, competitive aggression, i.e. noninjurious aggression used to maintain social dominance ranking, was not correlated with CSF 5-HIAA or NE. Females with above average CSF 5-HIAA prior to and following group formation were more likely to attain and maintain a high social dominance ranking within their social group than females with below average CSF 5-HIAA. The present findings indicate that CNS monoamine functioning in adult female rhesus macaques is traitlike, showing a high degree of interindividual stability across time and setting. These findings also suggest a role for serotonin in controlling impulses that regulate aggression and that competent social behavior among nonhuman primates may require average or above average serotonin functioning. C1 NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892. NICHHD,ANIM CTR,COMPARAT ETHOL LAB,POOLESVILLE,MD. NR 51 TC 164 Z9 164 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 1996 VL 14 IS 1 BP 67 EP 76 DI 10.1016/S0893-133X(96)80060-1 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA TQ832 UT WOS:A1996TQ83200007 PM 8719031 ER PT J AU Ketter, TA George, MS Kimbrell, TA Benson, BE Post, RM AF Ketter, TA George, MS Kimbrell, TA Benson, BE Post, RM TI Functional brain imaging, limbic function, and affective disorders SO NEUROSCIENTIST LA English DT Review DE cerebral blood flow and metabolism; positron emission tomography; single photon emission tomography; magnetic resonance spectroscopy; mood disorders ID MAGNETIC-RESONANCE SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; SEASONAL AFFECTIVE-DISORDER; GLUCOSE-METABOLISM; DEPRESSED-PATIENTS; UNIPOLAR DEPRESSION; SLEEP-DEPRIVATION; MAJOR DEPRESSION; BIPOLAR DISORDER AB For more than a century, mesial cerebral structures have been candidate substrates for the mediation of emotional experience. Although limbic structures were originally conceived as forming a midline ring, emerging evidence suggests that emotional processes may be related more closely to anterior paralimbic (anterior limbic and nearby cortical) regions than to posterior limbic regions, In addition, basal ganglia-thalamocortical circuits for various cerebral processes have been proposed, including one involving anterior paralimbic structures thought to mediate emotion, Recent brain imaging studies have advanced this thesis by demonstrating anterior paralimbic activation during affective arousal in healthy volunteers, The overwhelming majority of functional imaging studies of both primary and secondary depression has demonstrated decreased anterior paralimbic and prefrontal cortical activity, the latter of which often correlated with severity of depression and resolved with symptom remission. A few studies have noted increased activity in these same regions, which may reflect heterogeneity due to particular illness subtypes, Preliminary evidence has suggested that baseline functional abnormalities in these structures may relate to diagnostic subtypes and provide differential markers of therapeutic responses. New imaging methods with greater sensitivity, spatial and temporal resolution, and biochemical specificity promise to fuel further insights into the neurobiology of normal emotion in health, subtypes of affective disorders, and perhaps even improved targeting of therapeutic interventions. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,STANFORD,CA 94305. MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT RADIOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. NR 65 TC 75 Z9 77 U1 5 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD JAN PY 1996 VL 2 IS 1 BP 55 EP 65 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UV100 UT WOS:A1996UV10000014 ER PT J AU Wink, DA Grisham, MB Mitchell, JB Ford, PC AF Wink, DA Grisham, MB Mitchell, JB Ford, PC TI Direct and indirect effects of nitric oxide in chemical reactions relevant to biology SO NITRIC OXIDE, PT A - SOURCES AND DETECTION OF NO; NO SYNTHASE SE METHODS IN ENZYMOLOGY LA English DT Review ID WOODCHUCK HEPATITIS-VIRUS; N-NITROSATION REACTIONS; AQUEOUS-SOLUTION; SUPEROXIDE-DISMUTASE; HYDROXYL RADICALS; NITROGEN-DIOXIDE; MARMOTA-MONAX; OXIDATION; PEROXYNITRITE; KINETICS C1 UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA 93106. LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,SHREVEPORT,LA 71130. NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892. RP Wink, DA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702, USA. RI Ford, Peter/D-1826-2011 OI Ford, Peter/0000-0002-5509-9912 NR 81 TC 122 Z9 124 U1 2 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 268 BP 12 EP 31 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG02D UT WOS:A1996BG02D00003 PM 8782570 ER PT J AU Christodoulou, D Kudo, S Cook, JA Krishna, MC Miles, A Grisham, MB Murugesan, R Ford, PC Wink, DA AF Christodoulou, D Kudo, S Cook, JA Krishna, MC Miles, A Grisham, MB Murugesan, R Ford, PC Wink, DA TI Electrochemical methods for detection of nitric oxide SO NITRIC OXIDE, PT A - SOURCES AND DETECTION OF NO; NO SYNTHASE SE METHODS IN ENZYMOLOGY LA English DT Review ID RELEASE; NO; NITROSATION; ELECTRODE; KINETICS; RAT C1 NCI,RADIAT BIOL BRANCH,RADIAT BIOL SECT,BETHESDA,MD 20892. UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA 93106. LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,SHREVEPORT,LA 71130. MADURAI KAMARAJ UNIV,SCH CHEM,MADURAI 625021,TAMIL NADU,INDIA. RP Christodoulou, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702, USA. RI Ford, Peter/D-1826-2011 OI Ford, Peter/0000-0002-5509-9912 NR 25 TC 52 Z9 52 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 268 BP 69 EP 83 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG02D UT WOS:A1996BG02D00007 PM 8782574 ER PT J AU Nims, RW Cook, JC Krishna, MC Christodoulou, D Poore, CMB Miles, AM Grisham, MB Wink, DA AF Nims, RW Cook, JC Krishna, MC Christodoulou, D Poore, CMB Miles, AM Grisham, MB Wink, DA TI Colorimetric assays for nitric oxide and nitrogen oxide species formed from nitric oxide stock solutions and donor compounds SO NITRIC OXIDE, PT A - SOURCES AND DETECTION OF NO; NO SYNTHASE SE METHODS IN ENZYMOLOGY LA English DT Review ID WOODCHUCK HEPATITIS-VIRUS; MARMOTA-MONAX; OXIDATION; NITRATE; MECHANISM; KINETICS; AGENTS; NO C1 LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,SHREVEPORT,LA 71130. NCI,RADIAT BIOL BRANCH,RADIAT BIOL SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,CHEM SYNTH ANAL LAB,FREDERICK,MD 21702. RP Nims, RW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702, USA. NR 23 TC 153 Z9 154 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 268 BP 93 EP 105 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG02D UT WOS:A1996BG02D00009 PM 8782576 ER PT J AU Miles, AM Wink, DA Cook, JC Grisham, MB AF Miles, AM Wink, DA Cook, JC Grisham, MB TI Determination of nitric oxide using fluorescence spectroscopy SO NITRIC OXIDE, PT A - SOURCES AND DETECTION OF NO; NO SYNTHASE SE METHODS IN ENZYMOLOGY LA English DT Review ID CONTROLLED BIOLOGICAL RELEASE; FLUOROMETRIC-DETERMINATION; ESCHERICHIA-COLI; NITROSATION; NITRATE; AGENTS; CELLS; NUCLEOPHILES; MACROPHAGES; COMPLEXES C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. NCI,RADIAT BIOL SECT,RADIAT BIOL BRANCH,BETHESDA,MD 20892. RP Miles, AM (reprint author), LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,SHREVEPORT,LA 71130, USA. FU NCI NIH HHS [CA63641]; NIDDK NIH HHS [DK47663] NR 31 TC 123 Z9 125 U1 1 U2 12 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 268 BP 105 EP 120 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG02D UT WOS:A1996BG02D00010 PM 8782577 ER PT J AU Wink, DA Grisham, MB Miles, AM Nims, RW Krishna, MC Pacelli, R Teague, D Poore, CMB Cook, JA Ford, PC AF Wink, DA Grisham, MB Miles, AM Nims, RW Krishna, MC Pacelli, R Teague, D Poore, CMB Cook, JA Ford, PC TI Determination of selectivity of reactive nitrogen oxide species for various substrates SO NITRIC OXIDE, PT A - SOURCES AND DETECTION OF NO; NO SYNTHASE SE METHODS IN ENZYMOLOGY LA English DT Review ID NITRIC-OXIDE; OXIDATION; NITROSATION; INHIBITION; DIOXIDE; PROTEIN; PEROXYNITRITE; KINETICS; AGENTS; CELLS C1 NCI,RADIAT BIOL BRANCH,RADIAT BIOL SECT,BETHESDA,MD 20892. LOUISIANA STATE UNIV,DEPT PHYSIOL,MED CTR,SHREVEPORT,LA 71130. RP Wink, DA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702, USA. RI Ford, Peter/D-1826-2011 OI Ford, Peter/0000-0002-5509-9912 NR 26 TC 38 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 268 BP 120 EP 130 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG02D UT WOS:A1996BG02D00011 PM 8782578 ER PT J AU Keefer, LK Nims, RW Davies, KM Wink, DA AF Keefer, LK Nims, RW Davies, KM Wink, DA TI ''NONOates'' (1-substituted diazen-1-ium-1,2-diolates) as nitric oxide donors: Convenient nitric oxide dosage forms SO NITRIC OXIDE, PT A - SOURCES AND DETECTION OF NO; NO SYNTHASE SE METHODS IN ENZYMOLOGY LA English DT Review ID CONTROLLED BIOLOGICAL RELEASE; NUCLEOPHILES; COMPLEXES; PROLIFERATION; AGENTS; NO C1 GEORGE MASON UNIV,DEPT CHEM,FAIRFAX,VA 22030. NCI,RADIAT BIOL BRANCH,RADIAT BIOL SECT,BETHESDA,MD 20892. RP Keefer, LK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 18 TC 514 Z9 520 U1 4 U2 32 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1996 VL 268 BP 281 EP 293 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BG02D UT WOS:A1996BG02D00027 PM 8782594 ER PT B AU Grzesiek, S Vuister, GW Wang, AC Delaglio, F Bax, A AF Grzesiek, S Vuister, GW Wang, AC Delaglio, F Bax, A BE Rao, BDN Kemple, MD TI Recent developments in protein NMR spectroscopy SO NMR AS A STRUCTURAL TOOL FOR MACROMOLECULES: CURRENT STATUS AND FUTURE DIRECTIONS LA English DT Proceedings Paper CT International Symposium on NMR as a Structural Tool for Macromolecules - Current Status and Future Directions CY OCT 30-NOV 01, 1994 CL INDIANAPOLIS, IN C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45313-4 PY 1996 BP 117 EP 120 PG 4 WC Biochemical Research Methods; Biophysics; Spectroscopy SC Biochemistry & Molecular Biology; Biophysics; Spectroscopy GA BF84L UT WOS:A1996BF84L00009 ER PT B AU Clore, GM Fesik, SW Gorenstein, DG LeMaster, DM Markley, JL AF Clore, GM Fesik, SW Gorenstein, DG LeMaster, DM Markley, JL BE Rao, BDN Kemple, MD TI Extension of techniques to larger molecules - Panel discussion SO NMR AS A STRUCTURAL TOOL FOR MACROMOLECULES: CURRENT STATUS AND FUTURE DIRECTIONS LA English DT Proceedings Paper CT International Symposium on NMR as a Structural Tool for Macromolecules - Current Status and Future Directions CY OCT 30-NOV 01, 1994 CL INDIANAPOLIS, IN C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45313-4 PY 1996 BP 207 EP 219 PG 13 WC Biochemical Research Methods; Biophysics; Spectroscopy SC Biochemistry & Molecular Biology; Biophysics; Spectroscopy GA BF84L UT WOS:A1996BF84L00016 ER PT B AU Clore, GM Gronenborn, AM AF Clore, GM Gronenborn, AM BE Rao, BDN Kemple, MD TI Structures of multimeric proteins by NMR SO NMR AS A STRUCTURAL TOOL FOR MACROMOLECULES: CURRENT STATUS AND FUTURE DIRECTIONS LA English DT Proceedings Paper CT International Symposium on NMR as a Structural Tool for Macromolecules - Current Status and Future Directions CY OCT 30-NOV 01, 1994 CL INDIANAPOLIS, IN C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45313-4 PY 1996 BP 237 EP 242 PG 6 WC Biochemical Research Methods; Biophysics; Spectroscopy SC Biochemistry & Molecular Biology; Biophysics; Spectroscopy GA BF84L UT WOS:A1996BF84L00018 ER PT B AU Brooks, B Cohn, M James, TL Prendergast, FG Smith, JL AF Brooks, B Cohn, M James, TL Prendergast, FG Smith, JL BE Rao, BDN Kemple, MD TI NMR vis-a-vis other structural methods - Panel discussion SO NMR AS A STRUCTURAL TOOL FOR MACROMOLECULES: CURRENT STATUS AND FUTURE DIRECTIONS LA English DT Proceedings Paper CT International Symposium on NMR as a Structural Tool for Macromolecules - Current Status and Future Directions CY OCT 30-NOV 01, 1994 CL INDIANAPOLIS, IN C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 BN 0-306-45313-4 PY 1996 BP 327 EP 338 PG 12 WC Biochemical Research Methods; Biophysics; Spectroscopy SC Biochemistry & Molecular Biology; Biophysics; Spectroscopy GA BF84L UT WOS:A1996BF84L00024 ER PT J AU Ugur, O Kostakoglu, L Hui, ET Fisher, DR Garmestani, K Gansow, OA Cheung, NKV Larson, SM AF Ugur, O Kostakoglu, L Hui, ET Fisher, DR Garmestani, K Gansow, OA Cheung, NKV Larson, SM TI Comparison of the targeting characteristics of various radioimmunoconjugates for radioimmunotherapy of neuroblastoma: Dosimetry calculations incorporating cross-organ beta doses SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE radioimmunotherapy; radiation dosimetry; monoclonal antibody; neuroblastoma ID GD2-SPECIFIC MONOCLONAL-ANTIBODY; COLON-CARCINOMA XENOGRAFTS; B-CELL LYMPHOMA; NUDE-MICE; TUMOR-LOCALIZATION; FRAGMENTS; THERAPY; CANCER; BIODISTRIBUTION; RADIONUCLIDES AB To optimize the efficacy of radioimmunotherapy (RIT), the ideal antibody-radioisotope combinations should be used to deliver the highest tumor and the lowest normal tissue doses. In a mouse model, tumor and critical organ-absorbed doses delivered by different radioimmunoconjugates were calculated and compared. We used a Medical Internal Radiation Dosimetry (MIRD)-style mouse dosimetry model that incorporates cross-organ beta doses to make refined estimates of the radiation absorbed dose to tissues. Biodistribution data from neuroblastoma xenografted nude mice were used to estimate tumor, organ and bone marrow absorbed dose values for Y-90-3F8, I-131-3F8 and I-131-F(ab')(2) fragments. Immunoreactive fractions of the radiolabeled antibodies were comparable. Although tumor uptake of the radioiodinated and radiometal labeled 3F8 was much higher than that of the radioiodinated F(ab')(2) fragments (maximum percent injected dose per gram values were 39.4, 33.2 and 20.1 for I-131-3F8, Y-90-3F8 and I-131-F(ab')(2), respectively), tumor to nontumor ratios were higher for radioiodinated fragments (with the exception of tumor to kidney ratio). For the minimum tumor dose necessary for complete ablation, the bone marrow received 195, 278 and 401 cGy for I-131-F(ab')2, I-131-3F8 and Y-90/3F8, respectively. Tumor doses were 50.1, 232 and 992 cGy/MBq for I-131-F(ab')(2), I-131-3F8 and Y-90-3F8, respectively. Tumor to bone marrow dose, which is defined as the therapeutic index, was 21.5, 14.7 and 10.4 for I-131-F(ab')(2), I-131-3F8 and Y-90-3F8. I-131-F(ab')(2) fragments produced the highest therapeutic index but also the lowest tumor dose for radioimmunotherapy. Radiometal conjugated IgG produced the highest tumor dose but also the lowest therapeutic index. C1 MEM SLOAN KETTERING CANC CTR, DEPT PEDIAT, NEW YORK, NY 10021 USA. PACIFIC NW LAB, RICHLAND, WA 99352 USA. NIH, BETHESDA, MD 20892 USA. NR 39 TC 21 Z9 21 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 1996 VL 23 IS 1 BP 1 EP 8 DI 10.1016/0969-8051(95)02001-2 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TR546 UT WOS:A1996TR54600001 PM 9004907 ER PT J AU Benson, DA Boguski, M Lipman, DJ Ostell, J AF Benson, DA Boguski, M Lipman, DJ Ostell, J TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The GenBank sequence database continues to expand its data coverage, quality control, annotation content and retrieval services. GenBank is comprised of DNA sequences submitted directly by authors as well as sequences from the other major public databases. An integrated retrieval system, known as Entrez, contains data from GenBank and from the major protein sequence and structural databases, as well as related MEDLINE abstracts. Users may access GenBank over the Internet through the World Wide Web and through special client-server programs for text and sequence similarity searching. FTP, CD-ROM and e-mail servers are alternate means of access. RP Benson, DA (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 9 TC 119 Z9 122 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1996 VL 24 IS 1 BP 1 EP 5 DI 10.1093/nar/24.1.1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TR975 UT WOS:A1996TR97500001 PM 8594554 ER PT J AU Hollstein, M Shomer, B Greenblatt, M Soussi, T Hovig, E Montesano, R Harris, CC AF Hollstein, M Shomer, B Greenblatt, M Soussi, T Hovig, E Montesano, R Harris, CC TI Somatic point mutations in the p53 gene of human tumors and cell lines: Updated compilation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN CANCERS; DELETIONS; DNA AB In 1994 we described a list of similar to 2500 point mutations in the p53 gene of human tumors and cell lines which we had compiled from the published literature and made available electronically through the file server at the EMBL Data Library. This database, updated twice a year, now contains records on 4496 published mutations (July 1995 release) and can be obtained from the EMBL Outstation-the European Bioinformatics Institute (EBI) through the network or on CD-ROM. This report describes the criteria for inclusion of data in this database, a description of the current format and a brief discussion of the current relevance of p53 mutation analysis to clinical and biological questions. C1 EUROPEAN BIOINFORMAT INST,EMBL OUTSTN,CAMBRIDGE,ENGLAND. UNIV VERMONT,COLL MED,BURLINGTON,VT 05405. INST GENET MOLEC,INSERM,U301,F-75010 PARIS,FRANCE. NORWEGIAN RADIUM HOSP,INST CANC RES,N-0310 OSLO,NORWAY. INT AGCY RES CANC,F-69372 LYON 08,FRANCE. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP Hollstein, M (reprint author), GERMAN CANC RES CTR,NEUENHEIMER FELD 280,D-69120 HEIDELBERG,GERMANY. RI Hovig, Eivind/H-2474-2011; OI Hovig, Eivind/0000-0002-9103-1077; soussi, thierry/0000-0001-8184-3293 NR 26 TC 448 Z9 462 U1 0 U2 6 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1996 VL 24 IS 1 BP 141 EP 146 DI 10.1093/nar/24.1.141 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TR975 UT WOS:A1996TR97500032 PM 8594564 ER PT J AU Baxevanis, AD Landsman, D AF Baxevanis, AD Landsman, D TI Histone sequence database: A compilation of highly-conserved nucleoprotein sequences SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA POLYMERASE-II; TRANSCRIPTION; ALIGNMENT; OCTAMER; TOOL AB By searching the current protein sequence databases using sequences from human and chicken histones H1/H5, H2A, H2B, H3 and H4, a database of aligned histone protein sequences with statistically significant sequence similarity to the search sequences was constructed, In addition, a nucleotide sequence database of the corresponding coding regions for these proteins has been assembled, The region of each of the core histones containing the histone fold motif is identified in the protein alignments. The database contains >1300 protein and nucleotide sequences, All sequences and alignments in this database are available through the World Wide Web at http://www.ncbi.nlm.nih.gov/Baxevani/HISTONES. C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 17 TC 25 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 1 PY 1996 VL 24 IS 1 BP 245 EP 247 DI 10.1093/nar/24.1.245 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TR975 UT WOS:A1996TR97500057 PM 8594591 ER PT J AU Siddiqui, MA Ford, H George, C Marquez, VE AF Siddiqui, MA Ford, H George, C Marquez, VE TI Synthesis, conformational analysis, and biological activity of a rigid carbocyclic analogue of 2'-deoxyaristeromycin built on a bicyclo[3.1.0]hexane template SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article ID NUCLEOSIDES; ARISTEROMYCIN AB A new chiral synthesis of the pseudosugar synthon (1R,2S,4R,5S)-1-[(benzyloxy)methyl]-2-tert-butyloxy-4-hydroxybicyclo[3.1.0]hexane (12) is reported. This compound was used as a template for the construction of carbocyclic nucleoside 4, a conformationally rigid analogue of 2'-deoxyaristeromycin. The X-ray structure and H-1 NMR analysis confirmed the exclusive North [2'-exo ((2)E)] conformation of 4 which is vastly different from that of other non-rigid carbocyclic nucleosides. Compound 4 showed good in vitro antiviral activity against human cytomegalovirus and EBV with minimal cytotoxicity. C1 NCI,NIH,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,LAB MED CHEM,BETHESDA,MD 20892. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. NR 17 TC 75 Z9 75 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1996 VL 15 IS 1-3 BP 235 EP 250 DI 10.1080/07328319608002382 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TV075 UT WOS:A1996TV07500018 ER PT J AU Siddiqi, SM Ji, XD Melman, N Olah, ME Jain, R Evans, P Glashofer, M Padgett, WL Cohen, LA Daly, JW Stiles, GL Jacobson, KA AF Siddiqi, SM Ji, XD Melman, N Olah, ME Jain, R Evans, P Glashofer, M Padgett, WL Cohen, LA Daly, JW Stiles, GL Jacobson, KA TI A survey of nonxanthine derivatives as adenosine receptor ligands SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article ID RAT-BRAIN; ANTAGONISTS AB The binding affinities at rat A(1), A(2a), and A(3) adenosine receptors of a wide range of heterocyclic derivatives have been determined. Mono-, bi-, tricyclic and macrocyclic compounds were screened in binding assays, using either [H-3]PIA or [H-3]CGS 21680 in rat brain membranes or [I-125]AB-MECA in CHO cells stably transfected with rat A(3) receptors. Several new classes of adenosine antagonists (e.g. 5-oxoimidazopyrimidines and a pyrazoloquinazoline) were identified. Various sulfonylpiperazines, 11-hydroxytetrahydrocarbazolenine, 4H-pyrido[1,2a]pyrimidin-one, folic acid, and cytochalasin H and J bound to A(3) receptors selectively. Moreover, cytochalasin A, which bound to A(1) adenosine receptors with K-i value of 1.9 mu M, inhibited adenylyl cyclase in rat adipocytes, but not via reversible Al receptor binding. C1 NIDDKD,NIH,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. NIDDKD,NIH,PHARMACODYNAM SECT,BETHESDA,MD 20892. NIDDKD,NIH,BIOCHEM MECHANISMS SECT,BIOORGAN CHEM LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 40 TC 21 Z9 21 U1 0 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1996 VL 15 IS 1-3 BP 693 EP 717 DI 10.1080/07328319608002416 PG 25 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TV075 UT WOS:A1996TV07500052 PM 27043138 ER PT J AU Schwartz, JL Shklar, G AF Schwartz, JL Shklar, G TI Glutathione inhibits experimental oral carcinogenesis, p53 expression, and angiogenesis SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID VITAMIN-E; MULTISTAGE CARCINOGENESIS; BETA-CAROTENE; CANCER; PREVENTION; INDUCTION; MUTATIONS; MODEL; SKIN AB Previous studies have shown that reduced glutathione (GSH) inhibits experimental oral carcinogenesis in the hamster buccal pouch model. To gain further understanding of molecular mechanisms in the anticancer effect of GSH, these studies examined levels of p53 protein expression. 7,12-Dimethylbenz[a]anthracene (DMBA) was applied to the buccal pouches of 20 Syrian Golden hamsters (Mesocricetus auratus) in a 0.5% solution in mineral oil thrice weekly for 14 weeks. In 10 animals, 10 mg/kg reduced glutathione (GSH) in 0.5 ml of mineral oil was administered by mouth thrice weekly on days alternate to the DMBA painting. An additional 20 animals served as DMBA-untreated and GSH controls. At the termination of the experimental period, there were fewer tumors in the DMBA-GSH than in the DMBA tumor control group, and the tumors were smaller (tumor burden 315 vs. 3,040 mm(3)). Histologically, the DMBA-GSH group showed a marked reduction in dysplasia, carcinoma in situ, and invasive epidermoid carcinoma sites. Immunohistochemically, by use of monoclonal antibodies for wild-type p53 (PAb 246), changes were observed in protein expression levels at dysplastic sites and within the malignant tumors. Staining for p53 protein was slightly increased in dysplasia and squamous cell carcinoma in the tumor control animals (painted with DMBA) compared with the untreated controls that were free of tumors. In the GSH and DMBA treatment group, p53 protein expression levels were strongly increased in dysplastic and tumor sites. The significant inhibition of oral carcinogenesis associated with the administration of GSH was correlated with the increased levels of the wild-type p53 turner suppressor gene, suggesting its possible use as a biomarker for GSH chemoprevention. The inhibition of oral carcinogenesis by reduced GSH was also related to a very significant inhibition of tumor angiogenesis, defined by factor VIII staining. Thus angiogenesis inhibition may be an additional mechanism for antioxidant chemoprevention, and this suggests another possible biomarker for antioxidant chemoprevention. C1 NIDR,MOL EPIDEMIOL & ORAL DIS INDICATORS BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH DENT MED,DIV ORAL PATHOL,DEPT ORAL MED & DIAGNOST SCI,BOSTON,MA 02115. NR 22 TC 30 Z9 30 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1996 VL 26 IS 2 BP 229 EP 236 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA VE853 UT WOS:A1996VE85300010 PM 8875560 ER PT J AU De Luca, LM Tarone, R Huynh, M Jones, CS Chen, LC AF De Luca, LM Tarone, R Huynh, M Jones, CS Chen, LC TI Dietary retinoic acid inhibits mouse skin carcinogenesis irrespective of age at initiation SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID FEMALE SENCAR MICE; TUMORIGENESIS; ISOTRETINOIN; PREVENTION; PAPILLOMA; CARCINOMA; 2-STAGE; TUMORS AB In the two-stage protocol of skin carcinogenesis, the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) is applied to the skin of mice at around seven weeks of age. We previously performed DMBA initiation at three weeks of age to study the effect of pharmacological (30 mu g/g diet) dietary, retinoic acid (RA) on skin carcinogenesis. In this study we asked whether dietary pharmacological RA is equally effective against skin carcinogenesis when mice are initiated with (DMBA) at 7 weeks of age and then subjected to weekly applications of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or mezerein (MEZ) for 20 weeks. Similar to the three-week initiation protocol, high dietary RA inhibited papilloma incidence and yield in MEZ- but not in TPA-promoted female SENCAR mice. In addition, carcinoma incidence and yield were decreased by high dietary RA in TPA- as well as MEZ-treated mice. These data demonstrate that the high dietary RA diet is as effective in inhibiting papilloma and carcinoma formation when the DMBA is applied al seven weeks of age as at three weeks. RP De Luca, LM (reprint author), NCI, NIH,DIFFERENTIAT CONTROL SECT, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37, RM 3A17, BETHESDA, MD 20892 USA. NR 19 TC 12 Z9 12 U1 0 U2 0 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 1996 VL 25 IS 3 BP 249 EP 257 PG 9 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA UN293 UT WOS:A1996UN29300004 PM 8771568 ER PT J AU Rao, GN Edmondson, J Hildebrandt, PK Bruner, RH AF Rao, GN Edmondson, J Hildebrandt, PK Bruner, RH TI Influence of dietary protein, fat, and fiber on growth, blood chemistry, and tumor incidences in fischer 344 rats SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID BODY-WEIGHT; F344/N RATS; SURVIVAL; MICE AB Composition of diets may influence grow th, diseases, tumor rates, and responses to chemical treatment. For two fears, Fischer 344 rats were fed the NIH-07 open-formula nonpurified diet (similar to 23% protein, similar to 5% fat, and similar to 3.5% fiber) and nonpurified experimental diets (NTP-90, NTP-91, and NTP-92) containing lower protein and higher fat and fiber (14.6-15.3% protein, 7.2-8.5% fat, and 9.4-14% fiber) than the NIH-07 diet. Rats were evaluated for growth patterns, survival, hematology, serum chemistry, nephropathy, and tumor incidences. Growth patterns were similar in rats fed the experimental diets and in those fed the NIH-07 diet. However, in rats fed the experimental diets, the adult body weights were significantly (6-9%) lower and the survival at 110 weeks of age was significantly higher (15-20%) than in rats fed the NIH-07 diet. Lower protein content of experimental diets decreased the severity of nephropathy. Higher fat content of experimental diets appears to have decreased the incidence or delayed the development of leukemia and associated mortality in males. Higher fiber content of experimental diets appears to have delayed the development of mammary tumors and associated mortality in females. Higher fat and/or fiber of the experimental diets decreased the incidence of pheochromocytomas in males. The low,er protein and higher fat and fiber contents of the experimental diets decreased the spontaneous tumor burden in two-year studies. These studies indicate that diets for rats in long-term studies could be modified to decrease the severity of nephropathy and to decrease/delay the development of spontaneous tumors. C1 PATHCO,IJAMSVILLE,MD 21754. PATHOL ASSOCIATES INT,W CHESTER,OH 45069. RP Rao, GN (reprint author), NIEHS,NTP,MD B3-08,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 22 TC 9 Z9 9 U1 0 U2 0 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 1996 VL 25 IS 3 BP 269 EP 279 PG 11 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA UN293 UT WOS:A1996UN29300006 PM 8771570 ER PT J AU Hartman, AM Block, G Chan, W Williams, J McAdams, M Banks, WL Robbins, A AF Hartman, AM Block, G Chan, W Williams, J McAdams, M Banks, WL Robbins, A TI Reproducibility of a self-administered diet history questionnaire administered three times over three different seasons SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; ASSESSMENT INSTRUMENTS; TERM RECALL; OLDER MEN; VALIDITY; RELIABILITY; RECORDS; NUTRIENT; WOMEN; CAROTENOIDS AB The reproducibility of the widely, used Health Habits and History Questionnaire (HHHQ) for estimating ''usual past-year'' nutrient intake was examined. The HHHQ was self-administered on three occasions during three different seasons, 68 women (avg age 43 yrs) provided usable data for all three questionnaires in the appropriate seasons. Intraclass correlations (ICC) among the three administrations ranged from 0.56 (carotene) to 0.82 (fat as percentage of energy), with a median of 0.72. Thus, reliability was moderate to good, and season of administration/ordinality generally had little impact on ranking of individuals. The point estimates of intake of energy and a number of nutrients were higher in the first administration (winter). Except for dietary fiber and possibly carotene, most differences disappeared when adjusted for energy using a nutrient density approach, as well as using repeated-measures regression models. The higher intake in the first administration may be due more to either learning or fatigue effects rather than an effect of seasonal food availability on perceptions of ''usual'' intake. These data should be used in conjunction with validity data in the future to help evaluate the gain in precision of group means (and changes in these means) and improved estimates of odds ratios and correlations between nutrients and factors such as serum values, if a questionnaire is administered more than once. C1 UNIV CALIF BERKELEY,SCH PUBL HLTH,PUBL HLTH NUTR PROGRAM,BERKELEY,CA 94720. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DEPT BIOCHEM & MOLEC BIOPHYS,RICHMOND,VA 23298. ST ANTHONY HOSP CENT,DENVER,CO 80204. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. MED COLL VIRGINIA HOSP,DEPT DIETET,RICHMOND,VA 23298. RP Hartman, AM (reprint author), NCI,DIV CANC PREVENT & CONTROL,EPN ROOM 313,6130 EXECUTIVE BLVD,MSC 7344,BETHESDA,MD 20892, USA. RI Block, Gladys/E-3304-2010 NR 50 TC 50 Z9 50 U1 2 U2 3 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 1996 VL 25 IS 3 BP 305 EP 315 PG 11 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA UN293 UT WOS:A1996UN29300009 PM 8771573 ER PT J AU Trimble, CL Hildesheim, A Brinton, LA Shah, KV Kurman, RJ AF Trimble, CL Hildesheim, A Brinton, LA Shah, KV Kurman, RJ TI Heterogeneous etiology of squamous carcinoma of the vulva SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; HUMAN PAPILLOMAVIRUS DNA; CELL CARCINOMA; INSITU HYBRIDIZATION; WOMEN AB Objective: To correlate various previously identified risk factors, different histologic types, and the presence of human papillomaviruses (HPV) in squamous vulvar carcinomas and intraepithelial precursor lesions. Methods: Cases of squamous vulvar carcinomas and intraepithelial precursor lesions from a case-control study were analyzed by histologic type, the presence of HPV, and HPV type. These findings were correlated with demographic and interview data. Results: Significant differences (P < .001) in the prevalence of HPV DNA were noted between the following: 1) patients with high-grade vulvar intraepithelial neoplasia (VIN) (48 of 54 [88.9%]), 2) different types of squamous carcinomas, designated basaloid and warty carcinomas (18 of 21 [85.7%]), and 3) keratinizing squamous carcinoma (three of 48 [6.3%]). When the risk factor profiles for basaloid or warty carcinoma and keratinizing squamous carcinoma were compared, it was found that basaloid and warty carcinoma was significantly associated with the classical cervical cancer risk factors (lifetime number of sexual partners, age at first intercourse, abnormal Papanicolaou smears, venereal warts, low socioeconomic status, and cigarette smoking) whereas keratinizing squamous carcinoma was less strongly linked to these factors and in some cases not at all. The risk profile for VIN was similar to that of basaloid and warty carcinoma (with respect to sexual and reproductive history and smoking), although effects were weaker for some factors. Conclusion: The results of this study further support the view that vulvar carcinoma has two different etiologies, one related to HPV infection and one that is not. C1 NCI,BETHESDA,MD 20892. JOHNS HOPKINS HLTH INST,BALTIMORE,MD. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [CA 57550] NR 16 TC 120 Z9 123 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 1996 VL 87 IS 1 BP 59 EP 64 DI 10.1016/0029-7844(95)00351-7 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA TM645 UT WOS:A1996TM64500013 PM 8532267 ER EF