FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bracho, FA Bradley, MB Huges, RL Areman, E Davenport, V van de Ven, CV Cairo, MS AF Bracho, FA Bradley, MB Huges, RL Areman, E Davenport, V van de Ven, CV Cairo, MS TI Despite similar morphology and immunophenotypic characteristics, ex-vivo expanded dendritic cells (DC) derived from cord blood (CB) vs. mobilized adult peripheral blood (APB) plastic adherent mononuclear cells are significantly deficient in stimulating allogeneic T-cells. SO BLOOD LA English DT Meeting Abstract C1 Georgetown Univ Hosp, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Beckman Coulter, Miami, FL USA. NIH, Bethesda, MD 20892 USA. Columbia Univ, Childrens Hosp New York, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2764 BP 659A EP 659A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102777 ER PT J AU Watanabe, N DeRosa, SC Chao, NJ Herzenberg, LA Herzenberg, LA Roederer, M AF Watanabe, N DeRosa, SC Chao, NJ Herzenberg, LA Herzenberg, LA Roederer, M TI Dynamics of cytokine and perforin expression in T cells after allogeneic bone marrow transplantation: Possible predictors of GVHD. SO BLOOD LA English DT Meeting Abstract C1 IMSUT, Div Cell Proc, Tokyo, Japan. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. NCI, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Duke Univ, Bone Marrow Transplantat Program, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2771 BP 661A EP 661A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102784 ER PT J AU Michalek, J Collins, RH Hill, BJ Vitetta, ES Douek, DC AF Michalek, J Collins, RH Hill, BJ Vitetta, ES Douek, DC TI The emergence of specific T cell clones during the generation of GVHD. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA. NIH, Vaccine Res Ctr, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 71 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2783 BP 664A EP 664A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102796 ER PT J AU Medin, JA Liang, SB Qin, GJ Hou, J Fowler, D AF Medin, JA Liang, SB Qin, GJ Hou, J Fowler, D TI Retrovirally-transduced dendritic cell vaccines boost immunity to prostate antigen-expressing murine tumors. SO BLOOD LA English DT Meeting Abstract C1 Ontario Canc Inst, Div Expt Therapeut, Toronto, ON, Canada. NCI, Dept Expt Transplantat & Immunol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2915 BP 697A EP 698A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102928 ER PT J AU Wolins, NE Mondoro, TH Lozier, JN Eggerman, T Jones, E Morgan, RA Aguilar-Cordova, E Vostal, JG AF Wolins, NE Mondoro, TH Lozier, JN Eggerman, T Jones, E Morgan, RA Aguilar-Cordova, E Vostal, JG TI Intravenous administration of replication-incompetent adenovirus to rhesus monkeys induces thrombocytopenia by increasing in vivo platelet clearance. SO BLOOD LA English DT Meeting Abstract C1 US FDA, CBER, Bethesda, MD USA. NIH, NHGRI, Bethesda, MD USA. NIH, NCI, Bethesda, MD USA. Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2916 BP 698A EP 698A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102929 ER PT J AU Brown, KE Nguyen, QT Wong, S Heegaard, ED AF Brown, KE Nguyen, QT Wong, S Heegaard, ED TI Identification and characterization of a second novel human erythrovirus, A6. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Copenhagen, IMMI, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2964 BP 709A EP 709A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102977 ER PT J AU Horwitz, EM Hofmann, TJ Kelly, PF Vanin, EF Donahue, RE Brown, PS Dominici, M Persons, DA AF Horwitz, EM Hofmann, TJ Kelly, PF Vanin, EF Donahue, RE Brown, PS Dominici, M Persons, DA TI Nonadherent marrow stem cells give rise to blood and marrow mesenchymal stromal cells in mouse and monkey: Toward hematopoietic stem cell plasticity and the mesenchymal stem cell. SO BLOOD LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2981 BP 713A EP 714A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102994 ER PT J AU van der Kolk, DM Vellenga, E Scheffer, GL Muller, M Bates, SE Scheper, RJ de Vries, EGE AF van der Kolk, DM Vellenga, E Scheffer, GL Muller, M Bates, SE Scheper, RJ de Vries, EGE TI Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia. SO BLOOD LA English DT Meeting Abstract C1 Univ Groningen Hosp, Groningen, Netherlands. Free Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. Univ Wageningen, Wageningen, Netherlands. NIH, NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2989 BP 715A EP 716A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103002 ER PT J AU Frankel, AE Powell, BL Hall, PD Mone, AP Molnar, I Kreitman, RJ AF Frankel, AE Powell, BL Hall, PD Mone, AP Molnar, I Kreitman, RJ TI Phase I trial of a novel diphtheria toxin/GM-CSF fusion protein in refractory or relapsed acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract C1 Wake Forest Univ, Sch Med, Winston Salem, NC USA. Med Univ S Carolina, Charleston, SC 29425 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3014 BP 722A EP 722A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103027 ER PT J AU Chen, GB Miyazato, A Zeng, WH Maciejewski, JP Young, NS AF Chen, GB Miyazato, A Zeng, WH Maciejewski, JP Young, NS TI Distinct gene expression profile in CD34 cells from patients with specific karyotypic defects in myelodysplasia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3039 BP 728A EP 729A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103052 ER PT J AU Sloand, EM Kim, S Basu, A Nakamura, R Maciejewski, JP Risitano, A Barrett, AJ Young, NS AF Sloand, EM Kim, S Basu, A Nakamura, R Maciejewski, JP Risitano, A Barrett, AJ Young, NS TI Fas-mediated apoptosis is important in regulating cell replication and death in hematopoietic cells with trisomy 8 but not in cells with other chromosomal abnormalities. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3046 BP 730A EP 730A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103059 ER PT J AU Fry, TJ Sinha, M Thomas, EK Mackall, CL AF Fry, TJ Sinha, M Thomas, EK Mackall, CL TI Flt3 ligand: A potential new immunorestorative agent. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD USA. Immunex Corp, Div Extramural Res, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3064 BP 735A EP 735A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103077 ER PT J AU Chen, GB Kirby, M Young, NS Maciejewski, JP AF Chen, GB Kirby, M Young, NS Maciejewski, JP TI Superior growth of PNH progenitor cells in vitro is due to the higher apoptotic rate of progenitors of normal phenotype. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3118 BP 749A EP 749A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103131 ER PT J AU Rosenfeld, SJ Nunez, O Follmann, D Young, NS AF Rosenfeld, SJ Nunez, O Follmann, D Young, NS TI Long-term outcome in severe aplastic anemia is predicted by blood counts after treatment with intensive immunosuppression. SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Clin Res Informat, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3120 BP 749A EP 749A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103133 ER PT J AU Coignet, LJ Song, L Zlobin, A Brigaudeau, C Weijsen, S Jiang, Q Nacheva, E Davis, E Catovsky, D Grogan, T Staudt, L Fisher, RI Miele, L AF Coignet, LJ Song, L Zlobin, A Brigaudeau, C Weijsen, S Jiang, Q Nacheva, E Davis, E Catovsky, D Grogan, T Staudt, L Fisher, RI Miele, L TI Alteration of SMRT tumor suppressor function in transformed non-Hodgkin lymphomas. SO BLOOD LA English DT Meeting Abstract C1 Addenbrookes Hosp, Cambridge, England. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. Royal Marsden Hosp, London SW3 6JJ, England. Univ Arizona, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3164 BP 760A EP 760A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103177 ER PT J AU Lim, JB Provenzano, M Bettinotti, M Stroncek, DF AF Lim, JB Provenzano, M Bettinotti, M Stroncek, DF TI Identification of a new candidate HLA-A3 restricted CMV epitope as a target antigen to induce specific CMV cytotoxic T lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3244 BP 780A EP 780A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103257 ER PT J AU Nathwani, AC Davidoff, AM Hanawa, H Hu, YY Lozier, JN Hoffer, F Nikanorov, A Vanin, EF Slaughter, C Mandrell, TD Nienhuis, AW AF Nathwani, AC Davidoff, AM Hanawa, H Hu, YY Lozier, JN Hoffer, F Nikanorov, A Vanin, EF Slaughter, C Mandrell, TD Nienhuis, AW TI Sustained high level expression of human FIX following liver targeted delivery of recombinant adeno-associated virus encoding the human FIX gene in rhesus macaques. SO BLOOD LA English DT Meeting Abstract C1 UCL, London, England. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3251 BP 782A EP 782A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103264 ER PT J AU Otsuki, T Furukawa, Y Ikeda, K Endo, H Yamashita, T Shinohara, A Iwamatsu, A Ozawa, K Liu, JM AF Otsuki, T Furukawa, Y Ikeda, K Endo, H Yamashita, T Shinohara, A Iwamatsu, A Ozawa, K Liu, JM TI Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex. SO BLOOD LA English DT Meeting Abstract C1 Jichi Med Sch, Dept Hematol, Tochigi, Japan. Jichi Med Sch, Dept Mol Med, Tochigi, Japan. Jichi Med Sch, Dept Biol, Tochigi, Japan. Jichi Med Sch, Dept Biochem, Tochigi, Japan. Univ Tokyo, Dept Hematol Oncol, Tokyo, Japan. Cent Labs Key Technol, Prot Chem Sect, Kanagawa, Japan. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3253 BP 782A EP 783A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103266 ER PT J AU Alter, BP Rosenberg, PS AF Alter, BP Rosenberg, PS TI Cancer in Fanconi's anemia: A North American pilot survey. SO BLOOD LA English DT Meeting Abstract C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3257 BP 783A EP 783A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103270 ER PT J AU Gladwin, MT Schechter, AN Reiter, CD Cannon, RO AF Gladwin, MT Schechter, AN Reiter, CD Cannon, RO TI Reduced endothelial nitric oxide production in men with sickle cell anemia is associated with depletion of plasma S-nitrosothiols and nitric oxide scavenging by plasma heme complexes. SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NIDDK, Lab Chem Biol, NIH, Bethesda, MD USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3260 BP 784A EP 784A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103273 ER PT J AU Leigh, KR Wojda, U Njoroge, JM Aerbajinai, W Miller, JL AF Leigh, KR Wojda, U Njoroge, JM Aerbajinai, W Miller, JL TI Stem cell factor reprograms hemoglobin production among adult human erythroblasts. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Lab Chem Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3263 BP 785A EP 785A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103276 ER PT J AU Aoki, Y Tosato, G AF Aoki, Y Tosato, G TI STAT3-mediated constitutive expression of survivin in primary effusion lymphoma cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, Expt Transplantat & Immunol Dept, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3269 BP 786A EP 786A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103282 ER PT J AU Hematti, P Sloand, EM Albert, MR Yee, CL Childs, RW Barrett, JA Vogel, JC Dunbar, CE AF Hematti, P Sloand, EM Albert, MR Yee, CL Childs, RW Barrett, JA Vogel, JC Dunbar, CE TI Identification of keratinocyte stem cells originating from the donor graft following mobilized peripheral blood allogeneic transplantation. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3293 BP 792A EP 792A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103306 ER PT J AU Zhang, P Iwasaki-Arai, J Lodie, T Fenyus, ML Lekstrom-Himes, J Foerster, I Akashi, K Tenen, DG AF Zhang, P Iwasaki-Arai, J Lodie, T Fenyus, ML Lekstrom-Himes, J Foerster, I Akashi, K Tenen, DG TI C/EBP alpha deficiency blocks granulocytic differentiation at the common myeloid progenitor stage in both adult and fetal liver myelopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Harvard Inst Med, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. NIAID, LHD, Bethesda, MD USA. Tech Univ Munich, Inst Microbiol, Munich, Germany. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3297 BP 792A EP 793A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103310 ER PT J AU Herblot, S Aplan, PD Hoang, T AF Herblot, S Aplan, PD Hoang, T TI A gradient of E2A activity in B cell development. SO BLOOD LA English DT Meeting Abstract C1 Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada. NCI, Div Clin Sci, Med Branch, Dept Genet, Gaithersburg, MD USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3300 BP 793A EP 793A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103313 ER PT J AU Maciejewski, JR Risitano, AM Sloand, EM Nunez, O Young, NS AF Maciejewski, JR Risitano, AM Sloand, EM Nunez, O Young, NS TI Distinct clinical outcome for cytogenetic abnormalities evolving from aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3336 BP 802A EP 802A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103349 ER PT J AU Gutierrez, MI Ibrahim, MM Dale, JK Straus, SE Bhatia, KG AF Gutierrez, MI Ibrahim, MM Dale, JK Straus, SE Bhatia, KG TI Mutiple sequence variations in the Epstein-Barr virus BZLF1 gene promoter: Single nucleotide polymorphisms in the ZIA domain are associated with cellular clonality and malignancy. SO BLOOD LA English DT Meeting Abstract C1 King Faisal Specialist Hosp & Res Ctr, KFNCCC&R, Res Ctr, Riyadh 11211, Saudi Arabia. NIAID, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3348 BP 805A EP 805A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103361 ER PT J AU Orlic, D Kajstura, J Chimenti, S Limana, F Jakoniuk, I Quaini, F Nadal-Ginard, B Cline, A Leri, A Bodine, D Anversa, P AF Orlic, D Kajstura, J Chimenti, S Limana, F Jakoniuk, I Quaini, F Nadal-Ginard, B Cline, A Leri, A Bodine, D Anversa, P TI Cytokine-mobilized stem cells traffic to infarcted hearts and regenerate functional myocardium resulting in improved survival. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. New York Med Coll, Valhalla, NY 10595 USA. NR 0 TC 2 Z9 2 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3368 BP 810A EP 810A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103381 ER PT J AU Hematti, P Sellers, SE Agricola, BA Metzger, ME Donahue, RE Dunbar, CE AF Hematti, P Sellers, SE Agricola, BA Metzger, ME Donahue, RE Dunbar, CE TI Retroviral transduction efficiency of rhesus macaque G-CSF-SCF mobilized CD34+peripheral blood cells is superior to G-CSF alone or G-CSF+FLT3-L mobilized cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3392 BP 816A EP 816A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103405 ER PT J AU Alpan, O Kamala, T Velander, W Knight, J OSickey, T High, K Matzinger, P AF Alpan, O Kamala, T Velander, W Knight, J OSickey, T High, K Matzinger, P TI Milky way: An inexpensive and easy method of inducing tolerance to human F.IX. SO BLOOD LA English DT Meeting Abstract C1 NIAID, LCMI, NIH, Bethesda, MD 20892 USA. Virginia Tech, Blacksburg, VA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3430 BP 825A EP 825A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103443 ER PT J AU Stroncek, DF Rainer, T Cipolone, KM Noguchi, CT Klein, HG Schechter, AN Leitman, SF AF Stroncek, DF Rainer, T Cipolone, KM Noguchi, CT Klein, HG Schechter, AN Leitman, SF TI Hemoglobin S polymerization in sickle cell trait RBCs prevents effective leukocyte reduction by filtration. SO BLOOD LA English DT Meeting Abstract C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3442 BP 828A EP 828A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103455 ER PT J AU Leitman, SF Sharon, V Noguchi, CT Schechter, AN Klein, HG Stroncek, DF AF Leitman, SF Sharon, V Noguchi, CT Schechter, AN Klein, HG Stroncek, DF TI Collection of sickle cell trait red cells by apheresis allows effective leukocyte reduction by filtration. SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD USA. NIH, NIDDK, Biol Chem Lab, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3444 BP 829A EP 829A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103457 ER PT J AU Martinez, RV Widlund, H El-Hayek, K Ladd, C Sasaki, K Fisher, DE Ozato, K Golub, TR AF Martinez, RV Widlund, H El-Hayek, K Ladd, C Sasaki, K Fisher, DE Ozato, K Golub, TR TI The ETs protein TEL regulates the interferon gamma transcriptional response via ICSBP. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead MIT Ctr Genome Res, Cambridge, MA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3460 BP 833A EP 833A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103473 ER PT J AU Lam, DH Soloway, PD Tessarollo, L Aplan, PD AF Lam, DH Soloway, PD Tessarollo, L Aplan, PD TI Inhibition of hematopoietic differentiation - A potential mechanism of leukemogenesis by the NUP98-HOXD13 fusion gene. SO BLOOD LA English DT Meeting Abstract C1 Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY USA. Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY USA. NCI, Mouse Canc Genet Program, Neural Dev Grp, Frederick, MD USA. NCI, Canc Res Ctr, Genet Branch, Bethesda, MD USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3473 BP 836A EP 836A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103486 ER PT J AU Solomon, SR Tran, T Schindler, J Vitetta, E Barrett, AJ AF Solomon, SR Tran, T Schindler, J Vitetta, E Barrett, AJ TI T cell receptor (TCR) V beta-specific superantigen responses used as a model to optimize selective depletion of graft-versus-host disease (GVHD)-reacting T cells with an immunotoxin targeting the IL-2 receptor. SO BLOOD LA English DT Meeting Abstract C1 NIH, NHLBI, Stem Cell Autotransplantat Sect, Bethesda, MD USA. NIH, DTM, Cell Proc Sect, Bethesda, MD USA. Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3539 BP 852A EP 852A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103552 ER PT J AU Mena, O Igarashi, T Srinivasan, R Carvallo, C Takahashi, Y Re, F Young, NS Barrett, AJ Linehan, WM Childs, RW AF Mena, O Igarashi, T Srinivasan, R Carvallo, C Takahashi, Y Re, F Young, NS Barrett, AJ Linehan, WM Childs, RW TI Immunologic mechanisms involved in the graft-vs-tumor (GVT) effect in renal cell carcinoma (RCC) following nonmyeloablative allogeneic peripheral blood stem cell transplantation (NST). SO BLOOD LA English DT Meeting Abstract C1 NCI, Med & Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3555 BP 856A EP 856A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103568 ER PT J AU Confer, DL Haagenson, M Anderlini, P Fischer, J Leitman, S Kollman, C Rowley, SD Stroncek, DF Wingard, JR Anasetti, C AF Confer, DL Haagenson, M Anderlini, P Fischer, J Leitman, S Kollman, C Rowley, SD Stroncek, DF Wingard, JR Anasetti, C TI Collection of rhG-CSF-mobilized blood stem cells from 395 unrelated donors. SO BLOOD LA English DT Meeting Abstract C1 Natl Marrow Donor Program, Minneapolis, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Dusseldorf, Med Ctr, D-4000 Dusseldorf, Germany. Hackensack Univ, Med Ctr, Hackensack, NJ USA. NIH, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL 32611 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3560 BP 857A EP 858A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103573 ER PT J AU Anasetti, C Haagenson, M Kollman, C Matlack, M Anderlini, P Fischer, J Rowley, S Leitman, S Stroncek, D Wingard, JR Confer, D AF Anasetti, C Haagenson, M Kollman, C Matlack, M Anderlini, P Fischer, J Rowley, S Leitman, S Stroncek, D Wingard, JR Confer, D TI Transplantation of G-CSF-mobilized blood stem cells from unrelated donors. SO BLOOD LA English DT Meeting Abstract C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Dusseldorf, Med Ctr, ITZ, D-4000 Dusseldorf, Germany. Hackensack Univ, Med Ctr, Hackensack, NJ USA. NIH, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3561 BP 858A EP 858A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103574 ER PT J AU Antczak, C Karp, DR London, RE Bauvois, B AF Antczak, C Karp, DR London, RE Bauvois, B TI Reanalysis of the involvement of gamma-glutamyl transpeptidase in the cell activation process SO FEBS LETTERS LA English DT Article DE acivicin; apoptosis; differentiation; ectoprotease; proliferation; signaling ID DIPEPTIDYL PEPTIDASE-IV; SIGNAL-TRANSDUCTION; TRANSFERASE TRANSPEPTIDASE; ALANYL AMINOPEPTIDASE; GROWTH; INHIBITION; KINASE; PHOSPHORYLATION; NSC-163501; PATHWAYS AB The inhibitor of gamma -glutamyl transpeptidase (gamma -GT) acivicin modulates cellular responses including growth, myeloid maturation and apoptosis. Whether these effects result from the inhibition of gamma -GT enzyme activity remains unclear. We compared the cellular effects of acivicin against a more potent and specific inhibitor of gamma -GT (L-2-amino-4-boronobutanoic acid (L-ABBA)) in gamma -GT-negative (B lymphoblastoid Ramos) and gamma -GT-positive (myelomonocytie HL-60, y-GT-transfected Ramos) cell lines. Under non-oxidative stress conditions, acivicin-induced cell growth arrest, apoptosis and macrophage maturation occurred independent of gamma -GT While L-ABBA did not influence any of these processes. Acivicin triggered tyrosine phosphorylation and increased nuclear factor kappaB activity. Further insight into the role of gamma -GT in cellular processes is needed. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Inst Curie, Sect Rech, INSERM U365, F-75248 Paris 05, France. Univ Texas, SW Med Ctr, Dept Internal Med, Harold C Simmons Arthrit Res Ctr, Dallas, TX 75390 USA. Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Bauvois, B (reprint author), Inst Curie, Sect Rech, INSERM U365, F-75248 Paris 05, France. RI Bauvois, Brigitte/F-6776-2013 FU NIAID NIH HHS [R01 AI42772] NR 27 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 16 PY 2001 VL 508 IS 2 BP 226 EP 230 DI 10.1016/S0014-5793(01)03057-5 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 495PT UT WOS:000172350100012 PM 11718720 ER PT J AU Mottley, C Mason, RP AF Mottley, C Mason, RP TI Sulfur-centered radical formation from the antioxidant dihydrolipoic acid SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-LIPOIC ACID; MICROSOMAL LIPID-PEROXIDATION; ELECTRON-SPIN-RESONANCE; PULSE-RADIOLYSIS; DEPENDENT GENERATION; PHENOXYL RADICALS; HYPOCHLOROUS ACID; AQUEOUS-SOLUTIONS; INDUCED OXIDATION; HL-60 CELLS AB Lipoic acid and its reduced form, dihydrolipoic acid, are thought to be strong antioxidants. There are also reports of dihydrolipoic acid acting as a pro-oxidant under certain circumstances. This article reports the direct observation by ESR spectrometry of the disulfide radical anion and the spin trapping of the primary thiyl radical formed from the oxidation of dihydrolipoic acid through thiol pumping with phenol and horseradish peroxidase. The disulfide radical anion reacts rapidly with oxygen to form the reactive radical superoxide, which is also trapped. The radical species formed show a potential for pro-oxidant activity of this compound. Although antioxidants, in general, have been shown to have pro-oxidant potential, the pro-oxidant chemistry of dihydrolipoic acid has not been well characterized. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Luther Coll, Dept Chem, Decorah, IA 52101 USA. RP Mason, RP (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 45 TC 27 Z9 28 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 42677 EP 42683 DI 10.1074/jbc.M104889200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300007 PM 11546802 ER PT J AU Wallace, AD Cidlowski, JA AF Wallace, AD Cidlowski, JA TI Proteasome-mediated glucocorticoid receptor degradation restricts transcriptional signaling by glucocorticoids SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KAPPA-B-ALPHA; DOWN-REGULATION; ESTROGEN-RECEPTOR; GENE-EXPRESSION; 26S PROTEASOME; PHOSPHORYLATED SITES; MULTIPLE MECHANISMS; HORMONE RECEPTORS; PROTEIN STABILITY; UBIQUITIN SYSTEM AB Ligand-dependent down-regulation of the glucocorticoid receptor (GR) has been shown to limit hormone responsiveness, but the mechanisms involved in this process are poorly understood. The glucocorticoid receptor is a phosphoprotein that upon ligand binding becomes hyperphosphorylated, and recent evidence indicates that phosphorylation status of the glucocorticoid receptor plays a prominent role in receptor protein turnover. Because phosphorylation is a key signal for ubiquitination and proteasomal catabolism of many proteins, we evaluated whether the ubiquitin-proteasomal pathway had a role in glucocorticoid receptor down-regulation and the subsequent transcriptional response to glucocorticoids. Pretreatment of COS-1 cells expressing mouse glucocorticoid receptor with the proteasome inhibitor MG-132 effectively blocks glucocorticoid receptor protein down-regulation by the glucocorticoid dexamethasone. Interestingly, both MG-132 and a second proteasome inhibitor beta -lactone significantly enhanced hormone response of transfected mouse glucocorticoid receptor toward transcriptional activation of glucocorticoid receptor-mediated reporter gene expression. The transcriptional activity of the endogenous human glucocorticoid receptor in HeLa cells was also enhanced by MG-132. Direct evidence for ubiquitination of the glucocorticoid receptor was obtained by immunoprecipitation of cellular extracts from proteasome-impaired cells. Examination of the primary sequence of mouse, hu man, and rat glucocorticoid receptor has identified a candidate PEST degradation motif. Mutation of Lys-426 within this PEST element both abrogated ligand-dependent down-regulation of glucocorticoid receptor protein and simultaneously enhanced glucocorticoid receptor-induced transcriptional activation of gene expression. Unlike wild type GR, proteasomal inhibition failed to enhance significantly transcriptional activity of K426A mutant GR. Together these findings suggest a major role of the ubiquitin-proteasome pathway in regulating glucocorticoid receptor protein turnover, thereby providing a mechanism to terminate glucocorticoid responses. C1 NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 68 TC 235 Z9 248 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 42714 EP 42721 DI 10.1074/jbc.M106033200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300012 PM 11555652 ER PT J AU Mitchell, DC Niu, SL Litman, BJ AF Mitchell, DC Niu, SL Litman, BJ TI Optimization of receptor-G protein coupling by bilayer lipid composition I - Kinetics of rhodopsin-transducin binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METARHODOPSIN-II; PHOTORECEPTOR-MEMBRANES; LATERAL DIFFUSION; CRYSTAL-STRUCTURE; BOVINE RHODOPSIN; MOLECULAR ORDER; DISK MEMBRANES; CHOLESTEROL; PHOSPHOLIPIDS; LUMIRHODOPSIN AB The role of membrane composition in modulating the rate of G protein-receptor complex formation was examined using rhodopsin and transducin (G(t)) as a model system. Metarhodopsin II (MII) and MII-G(t) complex formation rates were measured, in the absence of GTP, via flash photolysis for rhodopsin reconstituted in 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (18:0,18:1PC) and 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0,22:6PC) bilayers, with and without 30 mol% cholesterol. Variation in bilayer lipid composition altered the lifetime of MII-G(t) formation to a greater extent than the lifetime of MII. MII-G(t) formation was fastest in 18:0,22:6PC and slowest in 18:0,18:1PC/30 mol% cholesterol. At 37 degreesC and a G(t) to photolyzed rhodopsin ratio of 1:1 in 18:0,22: 6PC bilayers, MII-G(t) formed with a lifetime of 0.6 +/-0.06 ms, which was not significantly different from the lifetime for MII formation. Incorporation of 30 mol% cholesterol slowed the rate of MII-G(t) complex formation by about 400% in 18:0,18:1PC, but by less than 25% in 18:0,22:6PC bilayers. In 18:0,22:6PC, with or without cholesterol, MII-G(t) formed rapidly after MII formed. In contrast, cholesterol in 18:0,18:IPC induced a considerable lag time in MII-G(t) formation after MII formed. These results demonstrate that membrane composition is a critical factor in determining the temporal response of a G protein-coupled signaling system. C1 NIAAA, Sect Fluorescence Studies, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. RP Litman, BJ (reprint author), NIAAA, Sect Fluorescence Studies, Lab Membrane Biochem & Biophys, Pk 5,Rm 158,12420 Parklawn Dr, Rockville, MD 20852 USA. NR 45 TC 82 Z9 84 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 42801 EP 42806 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300023 PM 11544258 ER PT J AU Niu, SL Mitchell, DC Litman, BJ AF Niu, SL Mitchell, DC Litman, BJ TI Optimization of receptor-G protein coupling by bilayer lipid composition II - Formation of metarhodopsin II-transducin complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FATTY-ACID DEFICIENCY; GTP-BINDING PROTEIN; DOCOSAHEXAENOIC ACID; CYTOPLASMIC LOOP; GAMMA-SUBUNITS; GUINEA-PIG; RHODOPSIN; MEMBRANES; CHOLESTEROL; EQUILIBRIUM AB The visual transduction system was used as a model to investigate the effects of membrane lipid composition on receptor-G protein coupling. Rhodopsin was reconstituted into large, unilamellar phospholipid vesicles with varying acyl chain unsaturation, with and without cholesterol. The association constant (K-alpha) for metarhodopsin II (MII) and transducin (G(t)) binding was determined by monitoring MII-G(t) complex formation spectrophotometrically. At 20 degreesC, in pH 7.5 isotonic buffer, the strongest MII-G(t) binding was observed in 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0,22:6PC), whereas the weakest binding was in 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (18:0,18:1PC) with 30 mol% cholesterol. Increasing acyl chain unsaturation from 18:0,18:1PC to 18:0,22:6PC resulted in a 3-fold increase in K-alpha. The inclusion of 30 mol% cholesterol in the membrane reduced K-alpha in both 18:0,22:6PC and 18:0,18:1PC. These findings demonstrate that membrane compositions can alter the signaling cascade by changing protein-protein interactions occurring predominantly in the hydrophilic region of the proteins, external to the lipid bilayer. These findings, if extended to other members of the superfamily of G protein-coupled receptors, suggest that a loss in efficiency of receptor-G protein binding is a contributing factor to the loss of cognitive skills, odor and spatial discrimination, and visual function associated with n-3 fatty acid deficiency. C1 NIAAA, Sect Fluorescence Studies, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. RP Litman, BJ (reprint author), NIAAA, Sect Fluorescence Studies, Lab Membrane Biochem & Biophys, Pk 5,Rm 158,12420 Parklawn Dr, Rockville, MD 20852 USA. NR 38 TC 77 Z9 78 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 42807 EP 42811 DI 10.1074/jbc.M105778200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300024 PM 11544259 ER PT J AU Pombo, I Martin-Verdeaux, S Iannascoli, B Le Mao, J Deriano, L Rivera, J Blank, U AF Pombo, I Martin-Verdeaux, S Iannascoli, B Le Mao, J Deriano, L Rivera, J Blank, U TI IgE receptor type 1-dependent regulation of a Rab3D-associated kinase - A possible link in the calcium-dependent assembly of snare complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNAPTIC-VESICLE FUSION; MAST-CELL SECRETION; SMALL G-PROTEINS; FC-EPSILON-RI; MEMBRANE-PROTEIN; TARGET MEMBRANE; RAB3 SUBFAMILY; EXOCYTOSIS; PHOSPHORYLATION; SYNTAXIN-4 AB Following activation through high affinity IgE receptors (Fc epsilon RI), mast cells release, within a few minutes, their granule content of inflammatory and allergic mediators. Fc epsilon RI-induced degranulation is a SNARE (soluble N-ethylmaleimide attachment protein receptors)-dependent fusion process. It is regulated by Rab3D, a subfamily member of Rab GTPases. Evidence exists showing that Rab3 action is calcium-regulated although the molecular mechanisms remain unclear. To obtain an understanding of Rab3D function we have searched for Rab3D-associated effectors that respond to allergic triggering through Fc epsilon RI. Using the RBL-2H3 mast cell line we detected a Ser/Thr kinase activity, termed here Rak3D (from Rab3D-associated kinase), because it was specifically co-immunoprecipitated with anti-Rab3D antibody. Rak3D activity, as measured by its auto- or transphosphorylation, was maximal in resting cells and decreased upon stimulation. The down-regulation of the observed activity was blocked with EGTA, but not with other degranulation inhibitors, suggesting that its activity functions downstream of calcium influx. We found that Rak3D phosphorylates the NH2-terminal regulatory domain of the t-SNARE syntaxin 4, but not syntaxin 2 or 3. The phosphorylation of syntaxin 4 decreased its binding to its partner SNAP23. Thus, we propose a novel phosphorylation-dependent mechanism by which Rab3D controls SNARE assembly in a calcium-dependent manner. C1 Inst Pasteur, Unite Immunoallergie, F-75724 Paris 15, France. NIAMS, Mol Inflammat Sect, NIH, Bethesda, MD 20892 USA. RP Blank, U (reprint author), Inst Pasteur, Unite Immunoallergie, 25-28 Rue Dr Roux, F-75724 Paris 15, France. NR 62 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 42893 EP 42900 DI 10.1074/jbc.M103527200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300036 PM 11555639 ER PT J AU Kalbfuss, B Mabon, SA Misteli, T AF Kalbfuss, B Mabon, SA Misteli, T TI Correction of alternative splicing of tau in frontotemporal dementia and Parkinsonism linked to chromosome 17 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; ANTISENSE OLIGONUCLEOTIDES; MESSENGER-RNA; NEURODEGENERATIVE DISORDERS; MICROTUBULE-BINDING; ALZHEIMERS-DISEASE; NEURONAL CELLS; SR PROTEINS; MUTATIONS; GENE AB Mutations in the human tau gene cause frontotemporal dementia and Parkinsonism associated with chromosome 17 (FTDP-17). One of the major disease mechanisms in FTDP-17 is the increased inclusion of tau exon 10 during pre-mRNA splicing. Here we show that modified oligonucleotides directed against the tau exon 10 splice junctions suppress inclusion of tau exon 10. The effect is mediated by the formation of a stable pre-mRNA-oligonucleotide hybrid, which blocks access of the splicing machinery to the pre-mRNA. Correction of tau splicing occurs in a tau minigene system and in endogenous tau RNA in neuronal pheochromocytoma cells and is specific to exon 10 of the tau gene. Antisense oligonucleotide-mediated exclusion of exon 10 has a physiological effect by increasing the ratio of protein lacking the microtubule-binding domain encoded by exon 10. As a consequence, the microtubule cytoskeleton becomes destabilized and cell morphology is altered. Our results demonstrate that alternative splicing defects of tau as found in FTDP-17 patients can be corrected by application of antisense oligonucleotides. These findings provide a tool to study specific tau isoforms in vivo and might lead to a novel therapeutic strategy for FTDP-17. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, 41 Lib Dr,Bldg 41, Bethesda, MD 20892 USA. NR 49 TC 56 Z9 58 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 42986 EP 42993 DI 10.1074/jbc.M105113200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300048 PM 11560926 ER PT J AU Ardon, O Bussey, H Philpott, C Ward, DM Davis-Kaplan, S Verroneau, S Jiang, B Kaplan, J AF Ardon, O Bussey, H Philpott, C Ward, DM Davis-Kaplan, S Verroneau, S Jiang, B Kaplan, J TI Identification of a Candida albicans ferrichrome transporter and its characterization by expression in Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR FACILITATOR SUPERFAMILY; MICROBIAL IRON TRANSPORT; PATHOGENIC BACTERIA; USTILAGO-MAYDIS; GENE; SIDEROPHORES; ANALOGS; ENCODES; COPPER; YEAST AB Saccharomyces cerevisiae can accumulate iron through the uptake of siderophore-iron. Siderophore-iron uptake can occur through the reduction of the complex and the subsequent uptake of iron by the high affinity iron transporter Fet3p/Ftr1p. Alternatively, specific siderophore transporters can take up the siderophore-iron complex. The pathogenic fungus Candida albicans can also take up siderophore-iron. Here we identify a C. albicans siderophore transporter, CaArn1p, and characterize its activity. CaARN1 is transcriptionally regulated in response to iron. Through expression studies in S. cerevisiae strains lacking endogenous siderophore transporters, we demonstrate that CaArn1p specifically mediates the uptake of ferrichrome-iron. Iron-ferrichrome and gallium-ferrichrome, but not desferri-ferrichrome, could competitively inhibit the uptake of iron from ferrichrome. Uptake of siderophore-iron resulting from expression of CaARN1 under the control of the MET25-promoter in S. cerevisiae was independent of the iron status of the cells and of Aft1p, the iron-sensing transcription factor. These studies demonstrate that the expression of CaArn1p is both necessary and sufficient for the non-reductive uptake of ferrichrome-iron and suggests that the transporter may be the only required component of the siderophore uptake system that is regulated by iron and Aft1p. C1 Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA. McGill Univ, Dept Biol, Montreal, PQ M3A 25T, Canada. NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. Elitra, Montreal, PQ H2X 248, Canada. RP Kaplan, J (reprint author), Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84132 USA. FU NCI NIH HHS [5 P30 CA 42014]; NIDDK NIH HHS [DK 30534] NR 34 TC 44 Z9 47 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 43049 EP 43055 DI 10.1074/jbc.M108701200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300056 PM 11562378 ER PT J AU Yabe, T Wilson, D Schwartz, JP AF Yabe, T Wilson, D Schwartz, JP TI NF kappa B activation is required for the neuroprotective effects of pigment epithelium-derived factor (PEDF) on cerebellar granule neurons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; GLUTAMATE-INDUCED NEUROTOXICITY; MANGANESE SUPEROXIDE-DISMUTASE; PRIMARY HIPPOCAMPAL-NEURONS; NECROSIS-FACTOR-ALPHA; APOPTOTIC CELL-DEATH; NEUROTROPHIC FACTOR; OXIDATIVE STRESS; FACTOR GENE; SURVIVAL FACTOR AB Pigment epithelium-derived factor (PEDF) protects immature cerebellar granule cells (1-3 days in vitro) against induced apoptosis and mature cells (5+ days in vitro) against glutamate toxicity, but its precise mechanism is still unknown. Because the transcription factor NF kappaB blocks cell death, including neuronal apoptosis, we have investigated the ability of PEDF to exert its effects via NF kappaB activation. PEDF induced an increased phosphorylation of I kappaB alpha, decreased levels of I kappaB proteins, and translocation of p65 (RelA) to the nucleus followed by a time-dependent increase of NF kappaB-DNA binding activity in both immature and mature neurons. The protective effects of PEDF against both induced apoptosis and glutamate toxicity were blocked by the addition of either the I kappaB kinase inhibitor BAY 11-7082 which inhibits the phosphorylation of I kappaB, or N-acetyl-Leu-Leu-norleucinal, which blocks. proteosome degradation of I kappaB, demonstrating that NF kappaB is required for the neuroprotective effects of PEDF. Reverse transcription-polymerase chain reaction analysis revealed that up-regulation of the anti-apoptotic genes for Bcl-2, Bcl-x, and manganese superoxide dismutase was observed in PEDF-treated immature but not mature neurons. Up-regulation of nerve growth factor, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor mRNA was long-lasting in mature neurons. These results suggest that PEDF promotes neuronal survival through activation of NF kappaB, which in turn induces expression of anti-apoptotic and/or neurotrophic factor genes. C1 NINCDS, NTFS, NIH, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NINCDS, NTFS, NIH, Bldg 36,Rm 4A31, Bethesda, MD 20892 USA. NR 63 TC 100 Z9 104 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 43313 EP 43319 DI 10.1074/jbc.M107831200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300089 PM 11553640 ER PT J AU Cheng, AW Chan, SL Milhavet, O Wang, SQ Mattson, MP AF Cheng, AW Chan, SL Milhavet, O Wang, SQ Mattson, MP TI p38 MAP kinase mediates nitric oxide-induced apoptosis of neural progenitor cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ACTIVATED PROTEIN-KINASE; N-TERMINAL KINASE; CENTRAL-NERVOUS-SYSTEM; AMYLOID BETA-PEPTIDE; ADULT HUMAN BRAIN; SIGNAL-TRANSDUCTION; NEURONAL APOPTOSIS; CYTOCHROME-C; NEURODEGENERATIVE DISORDERS; CASPASE ACTIVATION AB Neural progenitor cells (NPC) can proliferate, differentiate into neurons or glial cells, or undergo a form of programmed cell death called apoptosis. Although death of NPC occurs during development of the nervous system and in the adult, the underlying mechanisms are unknown. Here we show that nitric oxide (NO) can induce death of C17.2 NPC by a mechanism requiring activation of p38 MAP kinase, poly(ADP-ribose) polymerase, and caspase-3. Nitric oxide causes release of cytochrome c from mitochondria, and Bcl-2 protects the neural progenitor cells against nitric oxide-induced death, consistent with a pivotal role for mitochondrial changes in controlling the cell death process. Inhibition of p38 MAP kinase by SB203580 abolished NO-induced cell death, cytochrome c release, and activation of caspase-3, indicating that p38 activation serves as an upstream mediator in the cell death process. The antiapoptotic protein Bcl-2 protected NPC against nitric oxide-induced apoptosis and suppressed activation of p38 MAP kinase. The ability of nitric oxide to trigger death of NPC by a mechanism involving p38 MAP kinase suggests that this diffusible gas may regulate NPC fate in physiological and pathological settings in which NO is produced. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 4F02,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 106 TC 125 Z9 137 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 43320 EP 43327 DI 10.1074/jbc.M107698200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300090 PM 11555660 ER PT J AU Valasek, L Hasek, J Nielsen, KH Hinnebusch, AG AF Valasek, L Hasek, J Nielsen, KH Hinnebusch, AG TI Dual function of eIF3j/Hcr1p in processing 20 S pre-rRNA and translation initiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE HOMOLOG; P40/LAMININ RECEPTOR PRECURSOR; TRANS-ACTING FACTORS; RIBOSOMAL-SUBUNITS; ESCHERICHIA-COLI; PRT1 PROTEIN; YEAST; COMPLEX; GENES; EIF3 AB eIF3j/Hcr1p, a protein associated with eIF3, was shown to bind to, and stabilize, the multifactor complex containing eIFs 1, 2, 3, and 5 and Met-tRNA(i)(Met), whose formation is required for an optimal rate of translation initiation. Here we present evidence that eIF3j/Hcr1p is an RNA binding protein that enhances a late step in 40 S ribosome maturation involving cleavage of the 20 S precursor of 18 S rRNA in the cytoplasm. Immunofluorescence staining shows that eIF3j/Hcr1p is localized predominantly in the cytoplasm. The herl A mutant exhibits a decreased amount of 40 S subunits, hypersensitivity to paromomycin, and increased levels of 20 S pre-rRNA. Combining the hcr1 Delta mutation with drs2 Delta or rps0a Delta, deletions of two other genes involved in the same step of 40 S subunit biogenesis, produced a synthetic growth defect. p35, the human ortholog of eIF3j/Hcr1p, partially complemented the slow growth phenotype conferred by hcr1 Delta when overexpressed in yeast. heIF3j/p35 was found physically associated with yeast eIF3 and 43 S initiation complexes in vitro and in vivo. Because it did not complement the 40 S biogenesis defect of hcr1 Delta, it appears that heIF3j can substitute for eIF3j/Hcr1p only in translation initiation. We conclude that eIF3j/Hcr1p is required for rapid processing of 20 S to IS S rRNA besides its role in translation initiation, providing an intriguing link between ribosome biogenesis and translation. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Microbiol, CR-14220 Prague, Czech Republic. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, 6 Ctr Dr,Bldg 6A-B1A-13, Bethesda, MD 20892 USA. RI Valasek, Leos/I-5743-2014; Hasek, Jiri/H-2427-2014 NR 35 TC 45 Z9 45 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 16 PY 2001 VL 276 IS 46 BP 43351 EP 43360 DI 10.1074/jbc.M106887200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300094 PM 11560931 ER PT J AU Chen, SF Gunasekera, A Zhang, XP Kunkel, TA Ebright, RH Berman, HM AF Chen, SF Gunasekera, A Zhang, XP Kunkel, TA Ebright, RH Berman, HM TI Indirect readout of DNA sequence at the primary-kink site in the CAP-DNA complex: Alteration of DNA binding specificity through alteration of DNA kinking SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE catabolite activator protein (CAP); cAMP receptor protein (CRP); protein-DNA interaction; indirect readout; protein-induced DNA bending ID GENE ACTIVATOR PROTEIN; ESCHERICHIA-COLI; RECEPTOR PROTEIN; RECOGNITION; MUTATIONS; PROGRAM AB The catabolite activator protein (CAP) sharply bends DNA in the CAP-DNA complex, introducing a DNA kink, with a roll angle of similar to 40 degrees and a twist angle of similar to 20 degrees, between positions 6 and 7 of the DNA half-site, 5'-A(1)A(2)A(3)T(4)G(5)T(6)G(7)A(8)T(9)C(10)T(11)-3' ("primary kink"). CAP recognizes the base-pair immediately 5' to the primary-kink site, T:A(6), through an "indirect-readout" mechanism involving sequence effects on the energetics of primary-kink formation. CAP recognizes the base-pair immediately 3' to the primary-kink site, G:C-7, through a "direct-readout" mechanism involving formation of a hydrogen bond between Glu181 of CAP and G:C-7. Here, we report that substitution of the carboxylate sidechain of Glu181 of CAP by the one-methylene-group-shorter carboxylate side-chain of Asp changes DNA binding specificity at position 6 of the DNA half site, changing specificity for T:A(6) to specificity for C:G(6), and we report a crystallographic analysis defining the structural basis of the change in specificity. The Glu181 --> Asp substitution eliminates the primary kink and thus eliminates indirect-readout-based specificity for T:A(6). The Glu181 --> Asp substitution does not eliminate hydrogen-bond formation with G:C-7, and thus does not eliminate direct-readout-based specificity for G:C-7. (C) 2001 Academic Press. C1 Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. Rutgers State Univ, Waksman Inst, Piscataway, NJ 08854 USA. Howard Hughes Med Inst, Dept Chem, Waksman Inst, Piscataway, NJ 08854 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Berman, HM (reprint author), Rutgers State Univ, Dept Chem, 610 Taylor Rd, Piscataway, NJ 08854 USA. OI Ebright, Richard/0000-0001-8915-7140 FU NIGMS NIH HHS [GM21589, GM41376] NR 25 TC 44 Z9 45 U1 1 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 16 PY 2001 VL 314 IS 1 BP 75 EP 82 DI 10.1006/jmbi.2001.5090 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 495NA UT WOS:000172346200007 PM 11724533 ER PT J AU Dangi, B Pelupessey, P Martin, RG Rosner, JL Louis, JM Gronenborn, AM AF Dangi, B Pelupessey, P Martin, RG Rosner, JL Louis, JM Gronenborn, AM TI Structure and dynamics of MarA-DNA complexes: An NMR investigation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE MarA; DNA; promoter; NMR; backbone assignments ID MULTIPLE ANTIBIOTIC-RESISTANCE; GROUP HYDROGEN-EXCHANGE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; TRANSCRIPTIONAL ACTIVATION; BINDING DOMAIN; PROTEINS; PROMOTERS; SEQUENCE; REGULON AB An unanswered question regarding gene regulation is how certain proteins are capable of binding to DNA with high affinity at specific but highly degenerate consensus sequences. We have investigated the interactions between the Escherichia coli transcription factor, MarA, and its diverse binding sites using NMR techniques. Complete resonance assignments for the backbone of the MarA protein complexed with DNA oligomers corresponding to its binding sites at the mar, fumC, micF and the fpr promoters were obtained. Secondary structure analysis based on chemical shifts reveals that regions identified as helical in the X-ray structure of the MarA-mar complex are present in the solution structure, although some of the helices are less well defined. The chemical shift differences between the four complexes confirm that helix 3 and helix 6 constitute the major DNA-binding elements. However, in striking contrast with the X-ray data: (i) the protein appears to be present in two or more confirmations in each of the complexes; (ii) no slowly exchanging N-H-2 protons (indicative of hydrogen bonded groups) were observed by NMR for the two arginine residues proposed to form crucial hydrogen bonds in the X-ray structure; and (iii) regions at the N terminus, not observed in the X-ray structure, may be involved in DNA-binding. Taken together, the NMR results indicate that MarA in its complexes with DNA target sites is in a highly dynamic state, allowing for small but significant rearrangements of the side-chains and/or backbone to bind to the different DNA sequences. C1 NIDDKD, NIH, Lab Chem Phys, Bethesda, MD 20892 USA. NIDDKD, NIH, Lab Mol Biol, Bethesda, MD 20892 USA. RP Gronenborn, AM (reprint author), NIDDKD, NIH, Lab Chem Phys, Bethesda, MD 20892 USA. OI Gronenborn, Angela M/0000-0001-9072-3525 NR 26 TC 18 Z9 18 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 16 PY 2001 VL 314 IS 1 BP 113 EP 127 DI 10.1006/jmbi.2001.5106 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 495NA UT WOS:000172346200011 PM 11724537 ER PT J AU Chong, HS Garmestani, K Bryant, LH Brechbiel, MW AF Chong, HS Garmestani, K Bryant, LH Brechbiel, MW TI Synthesis of DTPA analogues derived from piperidine and azepane: Potential, contrast enhancement agents for magnetic resonance imaging SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CENTRAL ACETIC-ACID; RING EXPANSION; GADOLINIUM(III) COMPLEXES; MONOCLONAL-ANTIBODIES; IN-VIVO; STABILITY; LIGANDS; RELAXOMETRY; DENDRIMERS; BACKBONE AB Two DTPA derivatives (PIP-DTPA and AZEP-DTPA) as potential contrast enhancement agents in MRI are synthesized. The T1 and T2 relaxivities of their corresponding Gd(III) complexes are reported. At clinically relevant field strengths, the relaxivities of the complexes are comparable to that of the contrast agent, Gd(DTPA) which is in clinical use. The serum stability of the Gd-153-labeled complexes is assessed by measuring the release of Gd-153 from the ligands. The radiolabeled Gd chelates are found to be kinetically stable in human serum for up to at least 14 days without any measurable loss of radioactivity. C1 NCI, Chem Sect, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Chem Sect, NIH, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov NR 34 TC 31 Z9 31 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 16 PY 2001 VL 66 IS 23 BP 7745 EP 7750 DI 10.1021/jo0106344 PG 6 WC Chemistry, Organic SC Chemistry GA 492NQ UT WOS:000172174800026 PM 11701031 ER PT J AU Murabito, JM Evans, JC Larson, MG Kreger, BE Splansky, GL Freund, KM Moskowitz, MA Wilson, PWF AF Murabito, JM Evans, JC Larson, MG Kreger, BE Splansky, GL Freund, KM Moskowitz, MA Wilson, PWF TI Family breast cancer history and mammography - Framingham Offspring Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE family characteristics; mammography; smoking ID HEALTH INTERVIEW SURVEYS; SCREENING MAMMOGRAPHY; CIGARETTE-SMOKING; UNITED-STATES; PASSIVE SMOKING; ACTIVE EXPOSURE; INCREASED RISK; TOBACCO-SMOKE; WHITE WOMEN; AGE AB The authors examined mammography use according to family cancer history and identified predictors of recent use (less than or equal to2 years). Framingham Offspring Study participants in Framingham, Massachusetts, aged 40-79 years, completed a breast health questionnaire in 1996-1997. The study sample of women included 141 with a first-degree relative with breast cancer, 221 with a mother or sister(s) with other cancers, and 331 with a mother and sister(s) who participate in the Framingham Heart Study and did not report a history of cancer. Stepwise logistic regression analysis was used to identify predictors of recent mammography use. Among women with a family breast cancer history, 98% reported mammography use compared with 95% of other women. Recent mammography use was higher in women with a family breast cancer history (93%) compared with women with a family history of other cancer (80%) and women without a family history of cancer (84%) (p = 0.004). Odds ratios and 95% confidence intervals for significant predictors of recent mammography use were as follows: family history of breast cancer, 3.2 (95% confidence interval (CI): 1.4, 7.7); recent clinical breast examination, 17.4 (95% CI: 9.2, 32.8); and smoking, 0.4 (95% CI: 0.2, 0.7). Mammography use was high among women with a family breast cancer history. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Endocrinol Sect, Boston, MA 02118 USA. RP Murabito, JM (reprint author), NHLBI, Framingham Heart Dis Epidemiol Study, 5 Thurber St, Framingham, MA 01702 USA. OI Freund, Karen/0000-0002-9049-5574 FU NHLBI NIH HHS [N01-HC-38083] NR 45 TC 38 Z9 39 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2001 VL 154 IS 10 BP 916 EP 923 DI 10.1093/aje/154.10.916 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 492CJ UT WOS:000172149500007 PM 11700246 ER PT J AU Schroeder, JC Weinberg, CR AF Schroeder, JC Weinberg, CR TI Use of missing-data methods to correct bias and improve precision in case-control studies in which cases are subtyped but subtype information is incomplete SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE algorithms; bias (epidemiology); case-control studies; computer simulation; epidemiologic methods; logistic models ID MAXIMUM-LIKELIHOOD; EM ALGORITHM AB Histologic and genetic markers can sometimes make it possible to refine a disease into subtypes. In a case-control study, an attempt to subcategorize a disease in this way can be important to elucidating its etiology if the subtypes tend to result from distinct causal pathways. Using subtyped case outcomes, one can carry out either a case-case analysis to investigate etiologic heterogeneity or do polytomous logistic regression to estimate odds ratios specific to subtypes. Unfortunately, especially when such an analysis is undertaken after the study has been completed, it may be compromised by the unavailability of tissue specimens, resulting in missing subtype data for many enrolled cases. The authors propose that one can more fully use the available data, including that provided by cases with missing subtype, by using the expectation-maximization algorithm to estimate risk parameters. For illustration, they apply the method to a study of non-Hodgkin's lymphoma in the midwestern United States. The simulations then demonstrate that, under assumptions likely to hold in many settings, the approach eliminates bias that would arise if unclassified cases were ignored and also improves the precision of estimation. Under the same assumptions, empirical confidence interval coverage is consistent with the nominal 95%. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Schroeder, JC (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 16 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2001 VL 154 IS 10 BP 954 EP 962 DI 10.1093/aje/154.10.954 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 492CJ UT WOS:000172149500012 PM 11700251 ER PT J AU Hawkins, ME Pfleiderer, W Jungmann, O Balis, FM AF Hawkins, ME Pfleiderer, W Jungmann, O Balis, FM TI Synthesis and fluorescence characterization of pteridine adenosine nucleoside analogs for DNA incorporation SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE DNA; phosphoramidites; pteridine nucleoside analogs ID OLIGONUCLEOTIDES; ASSAY AB Two fluorescent adenosine analogs, 4-amino-6-methyl-8-(2-deoxy-beta -D-ribofuranosyl)-7(8H)-pteridone (6MAP) and 4-amino-2,6-dimethyl-8-(2'-deoxy-beta -D-ribofuranosyl)-7(8H)-pteridone (DMAP), have been synthesized as phosphoramidites. These probes are site-selectively incorporated into oligonucleotides using automated DNA synthesis. Relative quantum yields are 0.39 for 6MAP and 0.48 for DMAP as monomers and range from >0.01 to 0.11 in oligonucleotides. Excitation maxima are 310 (6MAP) and 330 nm (DMAP) and the emission maximum for each is 430 nm. Fluorescence decay curves of each are monoexponential exhibiting lifetimes of 3.8 and 4.8 ns for 6MAP and DMAP, respectively. When these probes are incorporated into oligonucleotides they display quenching of fluorescence intensity, increases in the complexity of decay curves, and decreases in mean lifetimes. Because these changes are apparently mediated by interactions with neighboring bases, spectral changes that occur as probe-containing oligonucleotides meet and react with other molecules provide a means of monitoring these interactions in real time. These probes are minimally disruptive to DNA structure as evidenced by melting temperatures of probe-containing oligonucleotides that are very similar to those of controls. Digestion of probe-containing oligonucleotides with P1 nuclease confirms probe stability as fluorescence levels are restored to those expected for each monomer. These adenosine analog probes are capable of providing information on DNA structure as it responds to binding or catalysis through interaction with other molecules. (C) 2001 Academic Press. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Konstanz, Fak Chem, D-7750 Constance, Germany. RP Hawkins, ME (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 11 TC 59 Z9 60 U1 3 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 15 PY 2001 VL 298 IS 2 BP 231 EP 240 DI 10.1006/abio.2001.5399 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 497JK UT WOS:000172451600010 PM 11700977 ER PT J AU Li, AQ Sowder, RC Henderson, LE Moore, SP Garfinkel, DJ Fisher, RJ AF Li, AQ Sowder, RC Henderson, LE Moore, SP Garfinkel, DJ Fisher, RJ TI Chemical cleavage at aspartyl residues for protein identification SO ANALYTICAL CHEMISTRY LA English DT Article ID HYDROLYSIS AB An alternative method to enzymatic digestion for protein identification by mass spectrometry has been developed that is based on chemical cleavage by formic acid. This method was tested on gel-purified apomyoglobin and BSA, as well as unknown proteins that cofractionate with Ty1-virus-like particles from Saccharomyces cerevisiae. Cleavage at aspartyl residues was found to be efficient and specific, and this specificity of cleavage lent itself easily to database searches. Parallel digestions using trypsin were also performed. The formic acid cleavage method generated comparable or better results than tryptic digestion for protein identification. C1 NCI, SAIC Frederick, Prot Chem Lab, AIDS Vaccine Program, Frederick, MD 21702 USA. NCI, SAIC Frederick, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Li, AQ (reprint author), NCI, SAIC Frederick, Prot Chem Lab, AIDS Vaccine Program, Bldg 469,Rm 240,POB B, Frederick, MD 21702 USA. RI Fisher, Robert/B-1431-2009 FU NCI NIH HHS [CO-56000] NR 11 TC 73 Z9 73 U1 2 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 15 PY 2001 VL 73 IS 22 BP 5395 EP 5402 DI 10.1021/ac010619z PG 8 WC Chemistry, Analytical SC Chemistry GA 493EQ UT WOS:000172209400007 PM 11816565 ER PT J AU Das, N Levine, RL Orr, WC Sohal, RS AF Das, N Levine, RL Orr, WC Sohal, RS TI Selectivity of protein oxidative damage during aging in Drosophila melanogaster SO BIOCHEMICAL JOURNAL LA English DT Article DE aconitase; hyperoxia; mitochondria; protein carbonylation; protein oxidation; oxidative stress ID CALORIC RESTRICTION; OXIDIZED PROTEINS; ESCHERICHIA-COLI; LIFE EXPECTANCY; MUSCA-DOMESTICA; ACONITASE; HYPEROXIA; INACTIVATION; MITOCHONDRIA; HOUSEFLIES AB The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative damage was accompanied by an approx. 50% loss in aconitase activity. An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidative stress causes age-associated losses in specific biochemical functions. C1 Univ So Calif, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90033 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. So Methodist Univ, Dept Biol Sci, Dallas, TX 75275 USA. RP Sohal, RS (reprint author), Univ So Calif, Dept Mol Pharmacol & Toxicol, 1985 Zonal Ave, Los Angeles, CA 90033 USA. RI Levine, Rodney/D-9885-2011 FU NIA NIH HHS [R01 AG17077] NR 46 TC 126 Z9 144 U1 1 U2 12 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 2001 VL 360 BP 209 EP 216 DI 10.1042/0264-6021:3600209 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497QL UT WOS:000172466900024 PM 11696009 ER PT J AU Rosenstein, DL Miller, FG Rubinow, DR AF Rosenstein, DL Miller, FG Rubinow, DR TI A curriculum for teaching psychiatric research bioethics SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bioethics; education; psychiatry; research; curriculum; teaching ID INFORMED CONSENT; RESEARCH ETHICS; SCHIZOPHRENIA; DISORDERS; CAPACITY; ISSUES AB Psychiatric research has received intense ethical scrutiny during the past decade. Changes in how studies are designed, reviewed by ethics boards, conducted, and reported in the literature have created a need for a systematic approach to teaching psychiatric research ethics to clinical researchers in training. The purpose of this article is to describe a model curriculum and comprehensive background reading list for training in psychiatric research bioethics. The curriculum was designed as an interactive seminar in a research fellowship program but can be adapted and incorporated into existing medical school and psychiatry residency training curricula. Participants in the seminar provide formal and informal evaluations of each session and the seminar as a whole. The seminar, now in it's third year, has been regularly attended and highly regarded by the NIMH research fellows who have participated. In response to recommendations by the participants, the content and organization of the seminar has been modified. Clinical research is both scientifically and ethically complex. Our initial experience with a formal curriculum in psychiatric research bioethics suggests that this educational activity has-been both meaningful and relevant for psychiatrists training to be clinical investigators. (C) 2001 Society of Biological Psychiatry. C1 NIMH, Off Clin Director, Bethesda, MD 20892 USA. RP Rosenstein, DL (reprint author), NIMH, Off Clin Director, Bldg 10,Room 3N242,10 Ctr Dr,MSC 1277, Bethesda, MD 20892 USA. NR 25 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2001 VL 50 IS 10 BP 802 EP 808 DI 10.1016/S0006-3223(01)01236-7 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 495RJ UT WOS:000172353900009 PM 11720699 ER PT J AU Kulkosky, J Culnan, DM Roman, J Dornadula, G Schnell, M Boyd, MR Pomerantz, RJ AF Kulkosky, J Culnan, DM Roman, J Dornadula, G Schnell, M Boyd, MR Pomerantz, RJ TI Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART SO BLOOD LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; LEUKEMIA-CELL LINE; CD-1 MOUSE SKIN; CD4(+) T-CELLS; HIV-1-INFECTED PATIENTS; PROMYELOCYTIC LEUKEMIA; NONPROMOTING PHORBOL; ESTABLISHMENT; TRANSCRIPTION AB Prostratin is a unique phorbol ester that stimulates protein kinase C activity but is nontumor promoting. Remarkably, prostratin is also able to inhibit de novo human immunodeficiency virus type 1 (HIV-1) infection yet up-regulate viral expression from latent proviruses. Prostratin's lack of tumor promotion, coupled with its ability to block viral spread yet induce latent proviral expression, prompted studies to determine whether this compound could serve as an inductive adjuvant therapy for patients treated with highly active antiretroviral therapy (HAART). The current experiments indicate that prostratin is a potent mitogen for mononuclear phagocytes possessing many of the activities of phorbol myristate acetate (PMA) with notable functional differences. Prostratin, like PMA, accelerates differentiation of the myeloid cell-lines, HL-60 and THP-1, as well as mononuclear phagocytes from bone marrow and peripheral blood. Enzyme-linked Immunosorbent assay and gene array analyses indicate significant changes in the expression of proteins and messenger RNA after treatment of cells with prostratin, consistent with phagocyte activation and differentiation. Prostratin blocks HIV-1 infection relating to down-regulation of CD4 receptor expression. The array analysis indicates a similar down-regulation of the HIV-1 coreceptors, CXCR4 and CCR5, and this may also reduce viral infectivity of treated host cells. Finally, prostratin is capable of up-regulating HIV-1 expression from CD8(+) T lymphocyte-depleted peripheral blood mononuclear cells of patients undergoing HAART. This novel observation suggests the agent may be an excellent candidate to augment HAART by inducing expression of latent HIV-1 with the ultimate goal of eliminating persistent viral reservoirs in certain individuals infected with HIV-1. (C) 2001 by The American Society of Hematology. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Med,Dorrance H Hamilton Labs, Div Infect Dis,Ctr Human Virol, Philadelphia, PA 19107 USA. Natl Canc Inst, Ctr Canc Res, Mol Targets Drug Discovery Program & Dev, Frederick, MD USA. RP Kulkosky, J (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Med,Dorrance H Hamilton Labs, Div Infect Dis,Ctr Human Virol, Philadelphia, PA 19107 USA. FU NIAID NIH HHS [R01AI46289] NR 36 TC 194 Z9 203 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2001 VL 98 IS 10 BP 3006 EP 3015 DI 10.1182/blood.V98.10.3006 PG 10 WC Hematology SC Hematology GA 492PW UT WOS:000172177600020 PM 11698284 ER PT J AU Aoki, Y Narazaki, M Kishimoto, T Tosato, G AF Aoki, Y Narazaki, M Kishimoto, T Tosato, G TI Receptor engagement by viral interleukin-6 encoded by Kaposi sarcoma-associated herpesvirus SO BLOOD LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Hematology CY DEC 01-05, 2000 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Hematol ID SIGNAL TRANSDUCER GP130; MODELING-GUIDED MUTAGENESIS; ENDOTHELIAL GROWTH-FACTOR; EPSTEIN-BARR-VIRUS; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; HUMAN IL-6; BINDING INTERFACE; MULTIPLE-MYELOMA; CYTOKINE AB Receptor usage by viral interleukin-6 (vIL-6), a virokine encoded by Kaposi sarcoma-associated herpesvirus, is an issue of controversy. Recently, the crystal structure of vIL-6 identified vIL-6 sites II and III as directly binding to glycoprotein (gp)130, the common signal transducer for the IL-6 family of cytokines. Site I of vIL-6, however, comprising the outward helical face of vIL-6, where human IL-6 (hIL-6) would interact with the specific a-chain IL-6 receptor (IL-6R), is accessible and not occupied by gp130. This study examined whether this unused vIL-6 surface is available for IL-6R binding. By enzyme-linked immunosorbent assay, vIL-6 bound to soluble gp130 (sgp130) but not to soluble IL-6R (sIL-6R). Using plasmon surface resonance, vIL-6 bound to sgp130 with a dissociation constant of 2.5 muM, corresponding to 1000-fold lower affinity than that of hIL-6/sIL-6R complex for gp130. sIL-6R neither bound to vIL-6 nor affected vIL-6 binding to gp130. In bioassays, vIL-6 activity was neutralized by 4 monoclonal antibodies (mAbs) recognizing a domain within vIL-6 site I, mapped to the C-terminal part of the AB-loop and the beginning of helix B. The homologous region in hIL-6 participates in site I binding to IL-6R. In addition, binding of vIL-6 to sgp130 was interfered with specifically by the 4 neutralizing anti-vIL-6 mAbs. Based on the vIL-6 crystal structure, the vIL-6 neutralizing mAbs; map outside the binding interface to gp130, suggesting that they either produce allosteric changes or block necessary conformational changes in vIL-6 preceding its binding to gp130. These results document that vIL-6 does not bind IL-6R and suggest that conformational change may be critical to vIL-6 function. (C) 2001 by The American Society of Hematology. C1 NCI, Ctr Canc Res, Med Branch, NIH, Bethesda, MD 20892 USA. Osaka Univ, Grad Sch Med, Dept Mol Med, Suita, Osaka, Japan. RP Aoki, Y (reprint author), NCI, Ctr Canc Res, Med Branch, NIH, 10 Ctr Dr,Rm 12N226 MSC1907, Bethesda, MD 20892 USA. RI Kishimoto, Tadamitsu/C-8470-2009; OI narazaki, masashi/0000-0002-5613-4409 NR 55 TC 46 Z9 47 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2001 VL 98 IS 10 BP 3042 EP 3049 DI 10.1182/blood.V98.10.3042 PG 8 WC Hematology SC Hematology GA 492PW UT WOS:000172177600025 PM 11698289 ER PT J AU Murphy, DL Li, Q Engel, S Wichems, C Andrews, A Lesch, KP Uhl, G AF Murphy, DL Li, Q Engel, S Wichems, C Andrews, A Lesch, KP Uhl, G TI Genetic perspectives on the serotonin transporter SO BRAIN RESEARCH BULLETIN LA English DT Article DE serotonin; transgenic (knockout/mutant) mice; personality; neuropsychiatric disorders; polymorphisms ID OBSESSIVE-COMPULSIVE DISORDER; ANXIETY-RELATED TRAITS; MESSENGER-RNA LEVELS; REUPTAKE INHIBITORS; ANIMAL-MODELS; BINDING-SITES; RAT-BRAIN; FUNCTIONAL POLYMORPHISM; PROMOTER POLYMORPHISM; EXPLORATORY-BEHAVIOR AB The serotonin transporter (5-HTT) is most well known as the site of action of the serotonin reuptake inhibitors, which were initially developed as antidepressants, but now are the most widely used agents in the treatment of many additional neuro psychiatric and related disorders. The discovery that the gene that expresses the 5-HTT possesses a functional promoter-region polymorphism, which is associated with temperament and personality traits such as anxiety and negative emotionality as well as some behaviors, led to many studies examining this polymorphism in individuals with different neuropsychiatric disorders. The subsequent development of mice with a targeted disruption of the 5-HTT in our laboratory has provided an experimental model to examine the many consequences of diminished (in +/-, heterozygote mice) or absent (in -/-, homozygote knockout mice) function of the 5-HTT. The 5-HTT-deficient mice were also crossed with other knockout mice, allowing the study of multiple neurobiologic dysfunctions. As multiple genes are probably involved in the expression of complex behaviors such as anxiety, as well as neuropsychiatric disorders, these more genetically complex mice may more closely model disorders with complex etiologies. Thus, the combination of these comparative human and mouse studies may extend the opportunities to examine genetic alterations from a novel "bottom-up" approach [gene knockout or partial gene knockout in a combinational gene x gene x (yet unknown) gene approach], which is complementary to the traditional "top-down" genetic approach based upon studies of individuals with diagnosed neuro psychiatric disorders and their family members. (C) 2001 Elsevier Science Inc. C1 NIMH, Clin Sci Lab, Ctr Clin, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Chem, University Pk, PA 16802 USA. Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. NIDA, Mol Neurobiol Res Branch, NIH, Bethesda, MD 20892 USA. RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, Ctr Clin, NIH, 10-3D41,10 Ctr Dr MSC 1264, Bethesda, MD 20892 USA. RI Andrews, Anne/B-4442-2011; Lesch, Klaus-Peter/J-4906-2013 OI Andrews, Anne/0000-0002-1961-4833; Lesch, Klaus-Peter/0000-0001-8348-153X NR 100 TC 141 Z9 143 U1 2 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV 15 PY 2001 VL 56 IS 5 BP 487 EP 494 DI 10.1016/S0361-9230(01)00622-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 505TE UT WOS:000172931000009 PM 11750794 ER PT J AU Joshi, BH Leland, P Asher, A Prayson, RA Varricchio, F Puri, RK AF Joshi, BH Leland, P Asher, A Prayson, RA Varricchio, F Puri, RK TI In situ expression of interleukin-4 (IL-4) receptors in human brain tumors and cytotoxicity of a recombinant IL-4 cytotoxin in primary glioblastoma cell cultures SO CANCER RESEARCH LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; CARCINOMA-CELLS; SARCOMA-CELLS; CANCER-CELLS; IN-VIVO; THERAPY; TOXIN; CHAIN AB We have reported that human malignant glioma cell lines express high levels of plasma membrane interleukin-4 receptors (IL-4R). We have also reported that biopsy/surgical samples or primary explant cell cultures from brain tumors express mRNA and protein for the IL-4R alpha chain, a primary IL4-binding protein. However, whether IL-4R are expressed in brain tumors ill situ has not been resolved. In addition, expression of IL-4R on the cell surface of various normal brain tissues is not known. We examined the expression of IL-4R by using a monoclonal antibody to the IL-4R alpha chain (also known as IL-4R beta) in surgical/biopsy samples of brain tumor tissues ti immunohistochemistry. Our data indicate that 15 of 18 glioblastoma multiforme (GBMs) tumors obtained from two different institutions and 12 other brain tumor samples are moderately to intensely positive for IL-4R alpha. In contrast, although IL-4R alpha mRNA was expressed, no IL-4R protein was detectable in two adult and one pediatric brain tissue specimens. In addition, a commercially available human neural tissue grid containing fixed tissues from various areas of brain showed no positive staining for the IL-4R alpha chain. IL-4R alpha expression was also demonstrated on astrocytoma grades I, II, and III. Because IL-4 cytotoxin comprised of a circularly permutated IL-4 and a mutated form of Pseudomonas exotoxin [IL4(38-37)-PE38KDEL] is cytotoxic to IL-4R-expressing cells, we tested whether primary GBM explant cell cultures are sensitive to IL-4 cytotoxin. Our data indicate that 13 of 15 GBM cell cultures were 25-74 times more sensitive to IL-4 cytotoxin compared with normal human astrocytes or the NT2 neuronal cell line. These observations indicate that human brain tumors ill situ overexpress IL-4R compared with normal brain tissues, thus confirming our previous conclusions that IL-4R in brain tumors may serve as an attractive target for anticancer therapy. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, Bethesda, MD 20892 USA. Carolina Neurosurg & Spine, Charlotte, NC 28207 USA. Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 20 TC 49 Z9 53 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2001 VL 61 IS 22 BP 8058 EP 8061 PG 4 WC Oncology SC Oncology GA 495AF UT WOS:000172317500002 PM 11719427 ER PT J AU Carreira, CM Nasser, SM di Tomaso, E Padera, TP Boucher, Y Tomarev, SI Jain, RK AF Carreira, CM Nasser, SM di Tomaso, E Padera, TP Boucher, Y Tomarev, SI Jain, RK TI LYVE-1 is not restricted to the lymph vessels: Expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis SO CANCER RESEARCH LA English DT Article ID NITRIC-OXIDE; HYALURONAN; RECEPTOR; CELLS; CD44 AB Lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 is thought to be restricted to lymph vessels and has been used as such to show that tumor lymphangiogenesis occurs on overexpression of lymphangiogenic factors in mouse tumor models. However, these studies have not yet been corroborated in human tumors. Here we show, first, that LYVE-1 is not exclusive to the lymph vessels. Indeed, LYVE-1 is also present in normal hepatic blood sinusoidal endothelial cells in mice and humans. Surprisingly, LYVE-1 is absent from the angiogenic blood vessels of human liver tumors and only weakly present in the microcirculation of regenerative hepatic nodules in cirrhosis, though both vessels are largely derived from the liver sinusoids. Second, we propose a novel approach to identify lymphatics in human and murine liver. By combining LYVE-1 and Prox 1 (a transcription factor) immunohistochemistry, we demonstrate that lymphatics are abundant in cirrhosis. In contrast, in human hepatocellular carcinoma and liver metastases, they are restricted to the tumor margin and surrounding liver. The absence of intratumor lymphatics in hepatocellular carcinomas and liver metastases may impair molecular and cellular transport in these tumors. Finally, the presence of LYVE-1 in liver sinusoidal endothelia suggests that LYVE-1 has functions beyond the lymph vascular system. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Stetle Lab Tumor Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Maine Med Ctr Res Inst, Ctr Mol Med, Scarborough, ME 04074 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Stetle Lab Tumor Biol, 100 Blossom St, Boston, MA 02114 USA. NR 28 TC 157 Z9 166 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2001 VL 61 IS 22 BP 8079 EP 8084 PG 6 WC Oncology SC Oncology GA 495AF UT WOS:000172317500006 ER PT J AU Touloukian, CE Leitner, WW Robbins, PF Rosenberg, SA Restifo, NP AF Touloukian, CE Leitner, WW Robbins, PF Rosenberg, SA Restifo, NP TI Mining the melanosome for tumor vaccine targets: P. polypeptide is a novel tumor-associated SO CANCER RESEARCH LA English DT Article ID T-LYMPHOCYTES; METASTATIC MELANOMA; TRANSGENIC MICE; ANTIGEN; TOLERANCE; DNA; IMMUNOTHERAPY; GP100; GENE AB To identify novel, tumor-specific target antigens for vaccine development, we studied immune responses to P.polypeptide, an M-r 110,000 integral melanosomal membrane protein associated with the Prader-Willi syndrome. Together with expressed sequence tag (EST) and serial analyses of gene expression (SAGE) library analyses, reverse transcription-PCR and Northern blotting verified that P.polypeptide expression was limited to melanoma and melanocytes. A single dominant epitope corresponding to positions 427-435 (IMLCLIAAV) was identified using allele-specific epitope forecasting combined with work in HLA-A*0201/K-b transgenic mice. This epitope was then used to generate de novo human P.polypeptide-specific CD8(+) T cells capable of recognizing P.polypeptide expressing human tumor cell lines in an HLA-A*0201-restricted fashion. Thus, P.polypeptide may be valuable in the creation of novel therapeutic anticancer vaccines. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 21 TC 13 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2001 VL 61 IS 22 BP 8100 EP 8104 PG 5 WC Oncology SC Oncology GA 495AF UT WOS:000172317500010 PM 11719435 ER PT J AU Wolfgang, CD Essand, M Lee, B Pastan, I AF Wolfgang, CD Essand, M Lee, B Pastan, I TI T-cell receptor gamma chain alternate reading frame protein (TARP) expression in prostate cancer cells leads to an increased growth rate and induction of caveolins and amphiregulin SO CANCER RESEARCH LA English DT Article ID INTERLEUKIN-1-BETA; MELANOMA; ALPHA AB Previously, we showed that prostate and prostate cancer cells express a truncated T-cell receptor gamma chain mRNA that uses an alternative reading frame to produce a novel nuclear T-cell receptor gamma chain alternate reading frame protein (TARP). TARP is expressed in the androgen-sensitive LNCaP prostate cancer cell line but not in the androgen-independent PC3 prostate cancer cell line, indicating that TARP may play a role in prostate cancer progression. To elucidate the function of TARP, we generated a stable PC3 cell line that expresses TARP in a constitutive manner. Expression of TARP in PC3 cells resulted in a more rapid growth rate with a 5-h decrease in doubling time. cDNA microarray analysis of 6538 genes revealed that caveolin 1, caveolin 2, amphiregulin, and melanoma growth stimulatory activity a were significantly up-regulated, whereas IL-1 beta was significantly down-regulated in PC3 cells expressing TARP. We also demonstrated that TARP expression is up-regulated by testosterone in LNCaP cells that express a functional androgen receptor. These results suggest that TARP has a role in regulating growth and gene expression in prostate cancer cells. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Uppsala, Div Clin Immunol, S-75185 Uppsala, Sweden. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 20 TC 26 Z9 26 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2001 VL 61 IS 22 BP 8122 EP 8126 PG 5 WC Oncology SC Oncology GA 495AF UT WOS:000172317500015 PM 11719440 ER PT J AU Phillips, JL Hayward, SW Wang, YH Vasselli, J Pavlovich, C Padilla-Nash, H Pezullo, JR Ghadimi, BM Grossfeld, GD Rivera, A Linehan, WM Cunha, GR Ried, T AF Phillips, JL Hayward, SW Wang, YH Vasselli, J Pavlovich, C Padilla-Nash, H Pezullo, JR Ghadimi, BM Grossfeld, GD Rivera, A Linehan, WM Cunha, GR Ried, T TI The consequences of chromosomal aneuploidy on gene expression profiles in a cell line model for prostate carcinogenesis SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CANCER; CARCINOMA; FIBROBLASTS; PROGRESSION AB Here we report the genetic characterization of immortalized prostate epithelial cells before and after conversion to tumorigenicity using molecular cytogenetics and microarray technology. We were particularly interested to analyze the consequences of acquired chromosomal aneuploidies with respect to modifications of gene expression profiles. Compared with nontumorigenic but immortalized prostate epithelium, prostate tumor cell lines showed high levels of chromosomal rearrangements that led to gains of 1p, 5, 11q, 12p, 16q, and 20q and losses of 1pter, 11p, 17, 20p, 21, 22, and Y. Of 5700 unique targets on a 6.5K cDNA microarray, similar to3% were subject to modification in expression levels; these included GRO-1, -2, IAP-1,- 2, MMP-9, and cyclin D1, which showed increased expression, and TRAIL, BRCA1, and CTNNA, which showed decreased expression. Thirty % of expression changes occurred in regions the genomic copy number of which remained balanced. Of the remainder, 42% of down-regulated and 51% of up-regulated genes mapped to regions present in decreased or increased genomic copy numbers, respectively. A relative gain or loss of a chromosome or chromosomal arm usually resulted in a statistically Significant increase or decrease, respectively, in the average expression level of all of the genes on the chromosome. However, of these genes, very few (e.g., 5 of 101 genes on chromosome 11q), and in some instances only two genes (MMP-9 and PROCR on chromosome 20q), were overexpressed by greater than or equal to1.7-fold when scored individually. Cluster analysis by gene function suggests that prostate tumorigenesis in these cell line models involves alterations in gene expression that may favor invasion, prevent apoptosis, and promote growth. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20817 USA. NCI, Genet Branch, NIH, Bethesda, MD 20817 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20817 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20817 USA. Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. RP Phillips, JL (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10 2B47,10 Ctr Dr, Bethesda, MD 20817 USA. NR 23 TC 142 Z9 148 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2001 VL 61 IS 22 BP 8143 EP 8149 PG 7 WC Oncology SC Oncology GA 495AF UT WOS:000172317500018 PM 11719443 ER PT J AU Kauraniemi, P Barlund, M Monni, O Kallioniemi, A AF Kauraniemi, P Barlund, M Monni, O Kallioniemi, A TI New amplified and highly expressed genes discovered in the ERBB2 amplicon in breast cancer by cDNA microarrays SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; ESOPHAGEAL-CARCINOMA; CELL-LINES; OVEREXPRESSION; HYBRIDIZATION; TUMORS; GRB7; CHROMOSOME-17; AMPLIFICATION; CHEMOTHERAPY AB Amplification of the ERBB2 oncogene at 17q12 has been well documented in breast cancer and has been shown to contribute to a poor clinical outcome. However, systematic surveys of copy number and expression levels of all genes within the 17q12 region have not been performed. Here, we used cDNA and comparative genomic hybridization microarray technologies to undertake a broad survey of genes involved in the 17q12 amplification in breast cancer. A chromosomal region-specific cDNA microarray containing 217 expressed sequence tag (EST) clones from 17q12 was constructed and used for parallel analysis of gene copy numbers and expression levels in seven breast cancer cell lines allowing direct identification of genes whose expression is elevated because of an increase in copy number in this chromosomal region. The copy number and expression survey identified 12 transcripts that showed a consistent pattern of increased copy number and expression in three or more of the 17q12-amplified cell lines. As expected, these included ERBB2 as well as the GRB7 and MLN64 genes previously shown to be coamplified with ERBB2. In addition, five other known genes and four uncharacterized ESTs were also found to be consistently activated by amplification in these breast cancer cell lines. Amplicon mapping by fluorescence in situ hybridization revealed a minimal common region of amplification containing four highly expressed genes, ERBB2, GRB7, MLN64, and an uncharacterized EST 48582. Furthermore, several other genes, although not located in the minimal common region of amplification, showed a correlated pattern of amplification and expression indicating that they might play a role in breast cancers with the 17q12 amplification. In conclusion, parallel analysis of gene copy number and expression levels by cDNA microarray can be used to directly identify candidate target genes involved in amplifications. Our results show that the 17q12 amplification in breast cancer leads to the simultaneous elevation of expression levels of several genes. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Tampere Univ, Inst Med Technol, Lab Canc Genet, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Miami, FL 33101 USA. RP Kallioniemi, A (reprint author), NHGRI, Canc Genet Branch, NIH, 49 Convent Dr,Rm 4B24, Bethesda, MD 20892 USA. OI Kallioniemi, Anne/0000-0003-3552-8158 NR 31 TC 173 Z9 174 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2001 VL 61 IS 22 BP 8235 EP 8240 PG 6 WC Oncology SC Oncology GA 495AF UT WOS:000172317500030 PM 11719455 ER PT J AU Nash, TE Pretell, J Garcia, HH AF Nash, TE Pretell, J Garcia, HH TI Calcified cysticerci provoke perilesional edema and seizures SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID TAENIA-SOLIUM TAENIASIS; NEUROCYSTICERCOSIS; EPILEPSY; LESIONS; EPIDEMIOLOGY; DIAGNOSIS; GLIOSIS AB In cases of cysticercosis, seizures and other symptoms occur in persons with only calcified brain lesions. The presence of perilesional edema has been documented in association with calcified lesions in symptomatic patients, but the frequency of this complication and characteristics of the patients who develop it are not known. Patients in Peru and the United States with neurocysticercosis, documented by positive results of serological testing and with only calcified lesions as shown using computerized tomography, were studied using magnetic resonance imaging. Perilesional edema was observed in slightly more than one-third of the patients, and some patients had frequent, severely disabling episodes. Those with an increased proportion of enhancing calcified lesions were more likely to show perilesional edema. Edema around calcified lesions is common in this population and is associated with seizures and neurological morbidity. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Inst Ciencias Neurol, Cysticercosis Unit, Lima, Peru. Univ Peruana Cayetano Heredia, Dept Microbiol, Lima, Peru. Univ Peruana Cayetano Heredia, Dept Pathol, Lima, Peru. RP Nash, TE (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4,Rm B1-06, Bethesda, MD 20892 USA. FU FDA HHS [FDR001107] NR 19 TC 46 Z9 47 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2001 VL 33 IS 10 BP 1649 EP 1653 DI 10.1086/323670 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 483TF UT WOS:000171651400005 PM 11595994 ER PT J AU Narita, M Hisada, M Thimmappa, B Stambaugh, JJ Ibrahim, E Hollender, ES Ashkin, D AF Narita, M Hisada, M Thimmappa, B Stambaugh, JJ Ibrahim, E Hollender, ES Ashkin, D TI Tuberculosis recurrence after directly observed therapy - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 AG Holley State TB Hosp, Lantana, FL 33462 USA. Florida Dept Hlth, Florida Bur TB Control & Prevent, Tallahassee, FL USA. Univ Miami, Sch Med, Div Pulm & Crit Care, Miami, FL USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Narita, M (reprint author), AG Holley State TB Hosp, 1199 W Lantana Rd, Lantana, FL 33462 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2001 VL 33 IS 10 BP 1798 EP 1798 DI 10.1086/323187 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 483TF UT WOS:000171651400037 ER PT J AU Owens, J Weinstein, J AF Owens, J Weinstein, J TI John Weinstein discusses information-intensive approaches to cancer drug discovery SO DRUG DISCOVERY TODAY LA English DT Editorial Material C1 NCI, NIH, Bethesda, MD 20892 USA. RP Owens, J (reprint author), NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD NOV 15 PY 2001 VL 6 IS 22 BP 1145 EP 1147 DI 10.1016/S1359-6446(01)02046-3 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 497BY UT WOS:000172433900005 ER PT J AU Michel, F Soler-Lopez, M Petosa, C Cramer, P Siebenlist, U Muller, CW AF Michel, F Soler-Lopez, M Petosa, C Cramer, P Siebenlist, U Muller, CW TI Crystal structure of the ankyrin repeat domain of Bcl-3: a unique member of the I kappa B protein family SO EMBO JOURNAL LA English DT Article DE Bcl-3; I kappa B proteins; NF-kappa B transcription factors ID CANDIDATE PROTOONCOGENE BCL-3; NUCLEAR EXPORT SIGNAL; ONCOPROTEIN BCL-3; P50 HOMODIMERS; REL PROTEINS; DNA-BINDING; ENCODES; ALPHA; REFINEMENT; COMPLEX AB I kappaB proteins associate with the transcription factor NF-kappaB via their ankyrin repeat domain. Bcl-3 is an unusual I kappaB protein because it is primarily nucleoplasmic and can lead to enhanced NF-kappaB-dependent transcription, unlike the prototypical I kappaB protein I kappaB alpha, which inhibits NF-kappaB activity by retaining it in the cytoplasm. Here we report the 1.9 Angstrom crystal structure of the ankyrin repeat domain of human Bcl-3 and compare it with that of I kappaB alpha bound to NF-kappaB. The two structures are highly similar over the central ankyrin repeats but differ in the N-terminal repeat and at the C-terminus, where Bcl-3 contains a seventh repeat in place of the acidic PEST region of I kappaB alpha Differences between the two structures suggest why Bcl-3 differs from I kappaB alpha in selectivity towards various NF-kappaB species, why Bcl-3 but not I kappaB alpha can associate with its NF-kappaB partner bound to DNA, and why two molecules of Bcl-3 but only one of I kappaB alpha can bind to its NF-kappaB partner. Comparison of the two structures thus provides an insight into the functional diversity of I kappaB proteins. C1 European Mol Biol Lab, Grenoble Outstn, F-38042 Grenoble 9, France. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Muller, CW (reprint author), European Mol Biol Lab, Grenoble Outstn, BP 181, F-38042 Grenoble 9, France. OI Mueller, Christoph/0000-0003-2176-8337 NR 49 TC 49 Z9 51 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 2001 VL 20 IS 22 BP 6180 EP 6190 DI 10.1093/emboj/20.22.6180 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 496NN UT WOS:000172403000002 PM 11707390 ER PT J AU Uptain, SM Sawicki, GJ Caughey, B Lindquist, S AF Uptain, SM Sawicki, GJ Caughey, B Lindquist, S TI Strains of [PSI+] are distinguished by their efficiencies of prion-mediated conformational conversion SO EMBO JOURNAL LA English DT Article DE amyloid; conformational conversion; epigenetics; [PSI+]; Sup35 ID DE-NOVO APPEARANCE; TRANSLATION TERMINATION EFFICIENCY; TRANSMISSIBLE MINK ENCEPHALOPATHY; SACCHAROMYCES-CEREVISIAE; YEAST PRION; RELEASE FACTOR; SUP35 PROTEIN; PROPAGATION; DETERMINANT; GENE AB Yeast prions are protein-based genetic elements that produce phenotypes through self-perpetuating changes in protein conformation. For the prion [PSI+] this protein is Sup35, which is comprised of a prion-determining region (NM) fused to a translational termination region. [PSI+] strains (variants) with different heritable translational termination defects (weak or strong) can exist in the same genetic background. [PSI+] variants are reminiscent of mammalian prion strains, which can be passaged in the same mouse strain yet have different disease latencies and brain pathologies. We found that [PSI+] variants contain different ratios of Sup35 in the prion and non-prion state that correlate with different translation termination efficiencies. Indeed, the partially purified prion form of Sup35 from a strong [PSI+] variant converted purified NM much more efficiently than that of several weak variants. However, this difference was lost in a second round of conversion in vitro. Thus, [PSI+] variants result from differences in the efficiency of prion-mediated conversion, and the maintenance of [PSI+] variants involves more than nucleated conformational conversion (templating) to NM alone. C1 Univ Chicago, Howard Hughes Med Inst, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Lindquist, S (reprint author), Univ Chicago, Howard Hughes Med Inst, Dept Mol Genet & Cell Biol, 5841 S Maryland Ave, Chicago, IL 60637 USA. FU NIGMS NIH HHS [GM57840, R01 GM057840] NR 64 TC 93 Z9 93 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 2001 VL 20 IS 22 BP 6236 EP 6245 DI 10.1093/emboj/20.22.6236 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 496NN UT WOS:000172403000007 PM 11707395 ER PT J AU Boehm, M Aguilar, RC Bonifacino, JS AF Boehm, M Aguilar, RC Bonifacino, JS TI Functional and physical interactions of the adaptor protein complex AP-4 with ADP-ribosylation factors (ARFs) SO EMBO JOURNAL LA English DT Article DE AP complex; ARF protein; brefeldin A; direct interaction; membrane recruitment ID GUANINE-NUCLEOTIDE EXCHANGE; GTPASE-ACTIVATING PROTEIN; GOLGI MEMBRANES; BREFELDIN-A; STRUCTURAL EXPLANATION; DEPENDENT INTERACTION; DOWNSTREAM EFFECTOR; SYNTHETIC LIPOSOMES; PHOSPHOLIPASE D1; APPENDAGE DOMAIN AB AP-4 is a member of the family of heterotetrameric adaptor protein (AP) complexes that mediate the sorting of integral membrane proteins in post-Golgi compartments. This complex consists of four subunits (epsilon, beta4, mu4 and sigma4) and localizes to the cytoplasmic face of the trans-Golgi network (TGN). Here, we show that the recruitment of endogenous AP-4 to the TGN in vivo is regulated by the small GTP-binding protein ARF1. In addition, we demonstrate a direct interaction of the epsilon and mu4 subunits of AP-4 with ARF1. epsilon binds only to ARF1.GTP and requires residues in the switch I and switch II regions of ARF1. In contrast, mu4 binds equally well to the GTP- and GDP-bound forms of ARF1 and is less dependent on switch I and switch II residues. These observations establish AP-4 as an ARF1 effector and suggest a novel mode of interaction between ARF1 and an AP complex involving both constitutive and regulated interactions. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 73 TC 62 Z9 62 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 2001 VL 20 IS 22 BP 6265 EP 6276 DI 10.1093/emboj/20.22.6265 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 496NN UT WOS:000172403000010 PM 11707398 ER PT J AU Gaba, A Wang, Z Krishnamoorthy, T Hinnebusch, AG Sachs, MS AF Gaba, A Wang, Z Krishnamoorthy, T Hinnebusch, AG Sachs, MS TI Physical evidence for distinct mechanisms of translational control by upstream open reading frames SO EMBO JOURNAL LA English DT Article DE Neurospora; ribosome reinitiation; ribosome scanning; Saccharomyces; uORF ID NEUROSPORA-CRASSA; MESSENGER-RNA; LEADER PEPTIDE; NASCENT-PEPTIDE; GENE-EXPRESSION; YEAST; ARGININE; RIBOSOME; INHIBITION; PROTEIN AB The Saccharomyces cerevisiae GCN4 mRNA 5'-leader contains four upstream open reading frames (uORFS) and the CPA1 leader contains a single uORF. To determine how these uORFs control translation, we examined mRNAs containing these leaders in cell-free translation extracts to determine where ribosomes were loaded first and where they were loaded during steady-state translation. Ribosomes predominantly loaded first at GCN4 uORF1. Following its translation, but not the translation of uORF4, they efficiently reinitiated protein synthesis at Gcn4p. Adding purified eIF2 increased reinitiation at uORFs 3 or 4 and reduced reinitiation at Gcn4p. This indicates that eIF2 affects the site of reinitiation following translation of GCN4 uORF1 in vitro. In contrast, for mRNA containing the CPA1 uORF, ribosomes reached the downstream start codon by scanning past the uORF. Addition of arginine caused ribosomes that had synthesized the uORF polypeptide to stall at its termination codon, reducing loading at the downstream start codon, apparently by blocking scanning ribosomes, and not by affecting reinitiation. The GCN4 and CPA1 uORFs thus control translation in fundamentally different ways. C1 Oregon Hlth & Sci Univ, ODI Sch Sci & Engn, Dept Biochem & Mol Biol, Beaverton, OR 97006 USA. NICHHD, Lab Eukaryot Gene Regulat, Bethesda, MD 20892 USA. Oregon Hlth & Sci Univ, Sch Med, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Sachs, MS (reprint author), Oregon Hlth & Sci Univ, ODI Sch Sci & Engn, Dept Biochem & Mol Biol, 20 000 NW Walker Rd, Beaverton, OR 97006 USA. FU NIGMS NIH HHS [GM47498-S, GM47498, R01 GM047498] NR 39 TC 93 Z9 94 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 2001 VL 20 IS 22 BP 6453 EP 6463 DI 10.1093/emboj/20.22.6453 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 496NN UT WOS:000172403000028 PM 11707416 ER PT J AU Vaisman, A Woodgate, R AF Vaisman, A Woodgate, R TI Unique misinsertion specificity of pol iota may decrease the mutagenic potential of deaminated cytosines SO EMBO JOURNAL LA English DT Article DE Rad30; translesion replication; UmuC; Y-family of DNA polymerases ID HUMAN DNA-POLYMERASE; ESCHERICHIA-COLI; MAMMALIAN-CELLS; XERODERMA-PIGMENTOSUM; MISMATCH REPAIR; FIDELITY; URACIL; BYPASS; DAMAGE; REPLICATION AB DNA polymerase iota (pol iota) is a distributive error-prone enzyme that can incorporate nucleotides opposite a variety of DNA lesions. Further elongation is, however, either substantially inhibited or completely abolished. Here, we provide evidence that pol tau can facilitate the efficient bypass of uracil and its derivatives as well as oxidized cytosine and guanine residues. The fidelity of translesion replication depends upon the lesion encountered. Correct nucleotides were inserted preferentially opposite 7,8-dihydro-8-oxo-guanine (8-oxoG) and 5-hydroxycytosine (5-OHC). However, when bypassing uracil, 5-hydroxyuracil (5-OHU) or 5,6-dihydrouracil (5,6-DHU), pol iota inserted T and G with a 4- to 26-fold preference over the Watson-Crick base, A. While the T:U, T:5-OHU and T:5,6-DHU mispairs were extended poorly, the G:U, G:5-OHU and G:5,6-DHU mispairs were extended with equal or greater efficiency than the correctly paired primer termini. Thus, pol iota -dependent misinsertion of G opposite uracil and its derivatives may actually provide a mechanism whereby mammalian cells can decrease the mutagenic potential of lesions formed via the deamination of cytosine. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RI Vaisman, Alexandra/C-3766-2013 OI Vaisman, Alexandra/0000-0002-2521-1467 NR 47 TC 80 Z9 91 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 2001 VL 20 IS 22 BP 6520 EP 6529 DI 10.1093/emboj/20.22.6520 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 496NN UT WOS:000172403000034 PM 11707422 ER PT J AU Dennis, K Fan, T Geiman, T Yan, QS Muegge, K AF Dennis, K Fan, T Geiman, T Yan, QS Muegge, K TI Lsh, a member of the SNF2 family, is required for genome-wide methylation SO GENES & DEVELOPMENT LA English DT Article DE Lsh; methylation; SNF2; SWI/SNF complex; chromatin ID HISTONE DEACETYLASE COMPLEX; DNA METHYLTRANSFERASE GENE; MAMMALIAN DEVELOPMENT; CPG-ISLAND; CYTOSINE; PROTEIN; CELLS; LYMPHOCYTES; INSTABILITY; EXPRESSION AB Methylation patterns of the mammalian genome are thought to be crucial for development. The precise mechanisms designating specific genomic loci for methylation are not known. Targeted deletion of Lsh results in perinatal lethality with a rather normal development. We report here, however, that Lsh(-/-) mice show substantial loss of methylation throughout the genome. The hypomethylated loci comprise repetitive elements and single copy genes. This suggests that global genomic methylation is not absolutely required for normal embryogenesis. Based on the similarity of Lsh to other SNF2 chromatin remodeling proteins, it suggests that alteration of chromatin affects global methylation patterns in mice. C1 Natl Canc Inst, SAIC, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RP Muegge, K (reprint author), Natl Canc Inst, SAIC, Mol Immunoregulat Lab, Frederick, MD 21702 USA. FU PHS HHS [N01-C0-56000] NR 35 TC 238 Z9 249 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 2001 VL 15 IS 22 BP 2940 EP 2944 DI 10.1101/gad.929101 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 495DJ UT WOS:000172324700004 PM 11711429 ER PT J AU Charite, J McFadden, DG Merlo, G Levi, G Clouthier, DE Yanagisawa, M Richardson, JA Olson, EN AF Charite, J McFadden, DG Merlo, G Levi, G Clouthier, DE Yanagisawa, M Richardson, JA Olson, EN TI Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer SO GENES & DEVELOPMENT LA English DT Article DE dHAND/HAND2; neural crest; branchial arches; endothelin-1; endothelin receptor A; Dlx6 ID BHLH TRANSCRIPTION FACTOR; RECEPTOR-DEFICIENT MICE; NEURAL CREST; A RECEPTOR; DEVELOPMENTAL EXPRESSION; MOUSE DEVELOPMENT; GENE-PRODUCTS; ZEBRAFISH; DIFFERENTIATION; CELL AB Neural crest cells play a key role in craniofacial development. The endothelin family of secreted polypeptides regulates development of several neural crest sublineages, including the branchial arch neural crest. The basic helix-loop-helix transcription factor dHAND is also required for craniofacial development, and in endothelin-1 (ET-1) mutant embryos, dHAND expression in the branchial arches is down-regulated, implicating it as a transcriptional effector of ET-1 action. To determine the mechanism that links ET-1 signaling to dHAND transcription, we analyzed the dHAND gene for cis-regulatory elements that control transcription in the branchial arches. We describe an evolutionarily conserved dHAND enhancer that requires ET-1 signaling for activity. This enhancer contains four homeodomain binding sites that are required for branchial arch expression. By comparing protein binding to these sites in branchial arch extracts from endothelin receptor A (EdnrA) mutant and wild-type mouse embryos, we identified D1x6, a member of the Distal-less family of homeodomain proteins, as an ET-1-dependent binding factor. Consistent with this conclusion, D1x6 was down-regulated in branchial arches from EdnrA mutant mice. These results suggest that D1x6 acts as an intermediary between ET-1 signaling and dHAND transcription during craniofacial morphogenesis. C1 Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75239 USA. Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75239 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75239 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75239 USA. Natl Canc Inst, IST, Lab Mol Morphogenesis, I-16132 Genoa, Italy. Natl Museum Nat Hist, CNRS, UMR 8572, Physiol Lab, Paris, France. RP Olson, EN (reprint author), Univ Texas, SW Med Ctr, Dept Mol Biol, 5323 Harry Hines Blvd, Dallas, TX 75239 USA. RI Clouthier, David/A-7062-2009; Levi, Giovanni/B-4416-2013 FU Telethon [TCP99003] NR 42 TC 85 Z9 86 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 2001 VL 15 IS 22 BP 3039 EP 3049 DI 10.1101/gad.931701 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 495DJ UT WOS:000172324700013 PM 11711438 ER PT J AU Colvin, MK Dunbar, K Grafman, J AF Colvin, MK Dunbar, K Grafman, J TI The effects of frontal lobe lesions on goal achievement in the water jug task SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID HUMAN WORKING-MEMORY; PLANNING ABILITY; RIGHT-HEMISPHERE; DECISION-MAKING; LONDON TASK; TOWER; ACTIVATION; IMPAIRMENTS; CORTEX; SYSTEM AB Patients with prefrontal cortex lesions are impaired on a variety of planning and problem-solving tasks. We examined the problem-solving performance of 27 patients with focal frontal lobe damage on the Water Jug task. The Water jug task has never been used to assess problem-solving ability in neurologically impaired patients nor in functional neuroimaging studies, despite sharing structural similarities Both other tasks sensitive to prefrontal cortex function, including the Tower of Hanoi, Tower of London, and Wisconsin Card Sorting Task (WCST), Our results demonstrate that the Water jug task invokes a unique combination of problem-solving and planning strategies, allowing a more precise identification of frontal lobe lesion patients' cognitive deficits. All participants (patients and matched controls) appear to be utilizing a hill-climbing strategy that does not require sophisticated planning; however, frontal lobe lesion patients (FLLs) struggled to make required "counterintuitive moves" not predicted by this strategy and found within both solution paths. Left and bilateral FLLs were more impaired than right FLLs. Analysis of the left hemisphere brain regions encompassed by the lesions of these patients found chat poor performance was linked to left dorsolateral prefrontal cortex damage, We propose that patients with left dorsolateral prefrontal cortex lesions have difficulty making a decision requiring the conceptual comparison of nonverbal stimuli, manipulation of select representations of potential solutions, and are unable to appropriately inhibit a response in keeping with the final goal. C1 NINCDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. McGill Univ, Montreal, PQ, Canada. Dartmouth Coll, Hanover, NH 03755 USA. RP Grafman, J (reprint author), NINCDS, Cognit Neurosci Sect, NIH, Room 5C205,Bldg 10,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 43 TC 29 Z9 31 U1 2 U2 5 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD NOV 15 PY 2001 VL 13 IS 8 BP 1129 EP 1147 DI 10.1162/089892901753294419 PG 19 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 500LW UT WOS:000172629900009 PM 11784450 ER PT J AU Bouchon, A Cella, M Grierson, HL Cohen, JI Colonna, M AF Bouchon, A Cella, M Grierson, HL Cohen, JI Colonna, M TI Cutting edge: Activation of NK cell-mediated cytotoxicity by a SAP-independent receptor of the CD2 family SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LINKED LYMPHOPROLIFERATIVE DISEASE; NATURAL-KILLER-CELLS; 2B4; CLONING; PROTEIN; GENE AB Some CD2 family receptors stimulate NK cell-mediated cytotoxicity through a signaling pathway, which is dependent on the recruitment of an adapter protein called SLAM-associated protein (SAP). In this work we identify a novel leukocyte cell surface receptor of the CD2 family called CD2-like receptor activating cytotoxic cells (CRACC). CRACC is expressed on cytotoxic lymphocytes, activated B cells, and mature dendritic cells, and activates NK cell-mediated cytotoxicity. Remarkably, although CRACC displays cytoplasmic motifs similar to those recruiting SAP, CRACC-mediated cytotoxicity occurs in the absence of SAP and requires activation of extracellular signal-regulated kinases-1/2. Thus, CRACC is a unique CD2-like receptor which mediates NK cell activation through a SAP-independent extracellular signal-regulated kinase-mediated pathway. C1 Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Basel Inst Immunol, Basel, Switzerland. NIH, Med Virol Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Colonna, M (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA. RI Cella, Marina/G-8850-2011; OI Colonna, Marco/0000-0001-5222-4987 NR 21 TC 103 Z9 104 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2001 VL 167 IS 10 BP 5517 EP 5521 PG 5 WC Immunology SC Immunology GA 491JZ UT WOS:000172106400001 PM 11698418 ER PT J AU Guthridge, JM Young, K Gipson, MG Sarrias, MR Szakonyi, G Chen, XJS Malaspina, A Donoghue, E James, JA Lambris, JD Moir, SA Perkins, SJ Holers, VM AF Guthridge, JM Young, K Gipson, MG Sarrias, MR Szakonyi, G Chen, XJS Malaspina, A Donoghue, E James, JA Lambris, JD Moir, SA Perkins, SJ Holers, VM TI Epitope mapping using the X-ray crystallographic structure of complement receptor type 2 (CR2)/CD21: Identification of a highly inhibitory monoclonal antibody that directly recognizes the CR2-C3d interface SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN LYMPHOCYTES-B; FOLLICULAR DENDRITIC CELLS; T-DEPENDENT ANTIGEN; CD21 LIGAND-BINDING; ACQUIRED-IMMUNITY; C3D; EXPRESSION; PROTEIN AB Complement receptor type 2 (CR2)/CD21 is a B lymphocyte cell membrane C3d/iC3b receptor that plays a central role in the immune response. Human CR2 is also the receptor for the EBV viral membrane glycoprotein gp350/220. Both C3d and gp350/220 bind CR2 within the first two of 15-16 repetitive domains that have been designated short consensus/complement repeats. Many mAbs react with human CR2; however, only one currently available mAb is known to block both C3d/iC3b find gp350/220 binding. We have used a recombinant form of human CR2 containing the short consensus/complement repeat 1-2 ligand-binding fragment to immunize Cr2(-/-) mice. Following fusion, we identified and further characterized four new anti-CR2 mAbs that recognize this fragment. Three of these inhibited binding of CR2 to C3d and gp350/220 in different forms. We have determined the relative inhibitory ability of the four mAbs to block ligand binding, and we have used overlapping peptide-based approaches to identify linear epitopes recognized by the inhibitory mAbs. Placement of these epitopes on the recently solved crystal structure of the CR2-C3d complex reveals that each inhibitory mAb recognizes a site either within or adjacent to the CR2-C3d contact site. One new mAb, designated 171, blocks CR2 receptor-ligand interactions with the greatest efficiency and recognizes a portion of the C3d contact site on CR2. Thus, we have created an anti-human CR2 mAb that blocks the C3d ligand by direct contact with its interaction site, and we have provided confirmatory evidence that the C3d binding site seen in its crystal structure exists in solution. C1 Univ Colorado, Hlth Sci Ctr, Dept Med & Immunol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80262 USA. Univ Penn, Prot Chem Lab, Philadelphia, PA 19104 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. UCL, Royal Free & Univ Coll Med Sch, Dept Biochem & Mol Biol, London, England. RP Holers, VM (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, Box B-115,4200 E 9th Ave, Denver, CO 80262 USA. EM michael.holers@uchsc.edu RI sarrias, maria rosa/D-6205-2014; OI sarrias, maria rosa/0000-0001-6929-8069; Lambris, John/0000-0002-9370-5776 FU NCI NIH HHS [R0-1 CA53615]; NIAID NIH HHS [R0-1 AI30040]; NIAMS NIH HHS [R0-1 AR45084, R0-1 AR01981] NR 52 TC 37 Z9 38 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2001 VL 167 IS 10 BP 5758 EP 5766 PG 9 WC Immunology SC Immunology GA 491JZ UT WOS:000172106400032 PM 11698449 ER PT J AU Umemura, T Alter, HJ Tanaka, E Yeo, AET Shih, JWK Orii, K Matsumoto, A Yoshizawa, K Kiyosawa, K AF Umemura, T Alter, HJ Tanaka, E Yeo, AET Shih, JWK Orii, K Matsumoto, A Yoshizawa, K Kiyosawa, K TI Association between SEN virus infection and hepatitis C in Japan SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID A-G HEPATITIS; POSTTRANSFUSION HEPATITIS; UNKNOWN ETIOLOGY; SEQUENCES; EXCRETION; PROTEIN; SANBAN; AREA AB There is a strong association between 2 SEN virus (SENV) variants (SENV-D and SENV-H) and transfusion-associated non-A-E hepatitis. In total, 200 subjects from a Japanese region where hepatitis C virus (HCV) is highly endemic and 194 persons from a contiguous area where HCV is not endemic were tested for SENV-D and SENV-H DNA by polymerase chain reaction. SENV DNA was detected equally in subjects from each area (56% prevalence in the area of high endemicity vs. 61% in the nonendemic area). Age-specific prevalence of SENV was similar to that of TT virus, with equal distribution at all ages in both areas; HCV was predominant in the elderly population. Alanine aminotransferase levels were significantly associated with HCV viremia but not with SENV viremia. SENV is a common infection that appears to have transmission routes and age-related prevalence that are distinct from those of HCV. No evidence was found that SENV caused hepatitis or worsened the course of hepatitis C. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. Shinshu Univ, Sch Med, Dept Internal Med 2, Matsumoto, Nagano 390, Japan. RP Umemura, T (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Rm 1C-711, Bethesda, MD 20892 USA. NR 19 TC 35 Z9 38 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2001 VL 184 IS 10 BP 1246 EP 1251 DI 10.1086/324210 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 487NZ UT WOS:000171883300003 PM 11679912 ER PT J AU Wang, SS Wheeler, CM Hildesheim, A Schiffman, M Herrero, R Bratti, MC Sherman, ME Alfaro, M Hutchinson, ML Morales, J Lorincz, A Burk, RD Carrington, M Erlich, HA Apple, RJ AF Wang, SS Wheeler, CM Hildesheim, A Schiffman, M Herrero, R Bratti, MC Sherman, ME Alfaro, M Hutchinson, ML Morales, J Lorincz, A Burk, RD Carrington, M Erlich, HA Apple, RJ TI Human leukocyte antigen class I and II alleles and risk of cervical neoplasia: results from a population-based study in Costa Rica SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the American-Association-for-Cancer-Research CY MAR 24-28, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Canc Res ID HUMAN-PAPILLOMAVIRUS INFECTION; NONRADIOACTIVE OLIGONUCLEOTIDE PROBES; INTRAEPITHELIAL NEOPLASIA; POLYMORPHISM; ASSOCIATION; CARCINOMA; DNA; CANCER; WOMEN AB To examine human leukocyte antigen (HLA) involvement in the development of all grades of cervical neoplasia, a nested case-control study of 10,077 women in Guanacaste, Costa Rica, was conducted. Participants had invasive cervical cancer, high-grade squamous intraepithelial lesions (HSILs; n = 166), or low-grade squamous intraepithelial lesions (LSILs); were positive for human papillomavirus (HPV) with no evidence of cervical neoplasia (n = 320); or were HPV negative with no evidence of cervical neoplasia but with a history of high-risk sexual behavior (n = 173). Compared with women who were HPV negative, women with HLA-DRB1*1301 were associated with decreased risk for cancer/HSILs (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.7) and for LSILs/HPV (OR, 0.6; 95% CI, 0.3-0.9). Women with both HLA-B*07 and HLA-DQB1*0302 had an 8.2-fold increased risk for cancer/HSILs (95% CI, 1.8-37.2) and a 5.3-fold increased risk for LSILs/HPV (95% CI, 1.2-23.7). These results support the hypothesis that multiple risk alleles are needed in order to increase risk for cervical neoplasia, but a single protective allele may be sufficient for protection. C1 NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Digene, Gaithersburg, MD USA. NCI, Lab Genet Divers, Div Basic Sci, Frederick, MD 21701 USA. Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Caja Costarricense Seguro Social, San Jose, Costa Rica. Women & Infants Hosp Rhode Isl, Dept Pathol, Providence, RI 02908 USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. Roche Mol Syst, Alameda, CA USA. RP Wang, SS (reprint author), NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA. RI apple, raymond/I-4506-2012 OI apple, raymond/0000-0002-8007-0345 FU NCI NIH HHS [N01CP21081, N01CP31061, CA-78527]; NIAID NIH HHS [AI/CA-32917] NR 15 TC 70 Z9 76 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2001 VL 184 IS 10 BP 1310 EP 1314 DI 10.1086/324209 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 487NZ UT WOS:000171883300011 PM 11679920 ER PT J AU Wilson, LE Umemura, T Astemborski, J Ray, SC Alter, HJ Strathdee, SA Vlahov, D Thomas, DL AF Wilson, LE Umemura, T Astemborski, J Ray, SC Alter, HJ Strathdee, SA Vlahov, D Thomas, DL TI Dynamics of SEN virus infection among injection drug users SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT, 2001 CL SAN FRANCISCO, CALIFORNIA SP Infect Dis Soc Amer ID HEPATITIS AB SEN virus (SENV) is a recently discovered group of DNA viruses whose members (SENV-D and SENV-H) are linked to posttransfusion hepatitis. Of 397 injection drug users (IDUs) in Baltimore, Maryland, SENV-D infection was detected by polymerase chain reaction in serum samples from 130 (32.7%) and SENV-H infection in 149 (37.5%). Of 41 IDUs in whom SENV-D DNA was initially detected, retesting for viral persistence a median of 9.3 years later detected SENV-D in 25 (61.0%), whereas SENV-H was detected on retesting in only 14 (26.9%) of 52 IDUs in whom the virus was originally found. Reinfection was apparent (>5% nucleotide difference) in 77.8% of IDUs who repeatedly tested positive for SENV-D DNA and in 55.6% of those who repeatedly tested positive for SENV-H DNA. Among Baltimore IDUs, SENV-D and SENV-H infections are common and dynamic, including both viral clearance and reinfection. The clinical significance of SENV infection in this setting remains unknown. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. RP Thomas, DL (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, 424 N Bond St, Baltimore, MD 21231 USA. RI Strathdee, Steffanie/B-9042-2009; Ray, Stuart/B-7527-2008 OI Ray, Stuart/0000-0002-1051-7260 FU NIDA NIH HHS [DA-04334, DA-10627, DA-12568] NR 15 TC 30 Z9 35 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2001 VL 184 IS 10 BP 1315 EP 1319 DI 10.1086/324001 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 487NZ UT WOS:000171883300012 PM 11679921 ER PT J AU Clark, RA Mulligan, K Stamenovic, E Chang, B Watts, H Andersen, J Squires, K Benson, C AF Clark, RA Mulligan, K Stamenovic, E Chang, B Watts, H Andersen, J Squires, K Benson, C TI Frequency of anovulation and early menopause among women enrolled in selected adult AIDS clinical trials group studies SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED WOMEN; MENSTRUAL-CYCLE; AGE AB To obtain information on the prevalence of anovulation and early menopause and on pituitary-gonadal function among human immunodeficiency virus type 1-infected women, a study was undertaken that used stored serum samples from women aged 20-42 years who participated in selected Adult AIDS Clinical Trials Group protocols. Defined progesterone and follicle-stimulating hormone (FSH) levels were considered presumptive evidence of ovulation and of menopause, respectively. Anovulation occurred in 16 (48%) of 33 women for whom progesterone levels were tested; early menopause occurred in 2 (8%) of 24 women for whom FSH levels were tested. No statistically significant differences were seen in the demographic and clinical characteristics of anovulatory and ovulatory women, although women who ovulated had higher CD4 T cell counts and were less likely to have reported a recent change in menstrual periods. These data support the findings of prior studies of increased frequency of amenorrhea and/or irregular menstrual cycles, particularly among women with lower CD4 T cell counts. C1 Louisiana State Univ, Hlth Sci Ctr, HIV Outpatient Program, New Orleans, LA 70112 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ So Calif, Los Angeles, CA USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. NICHHD, NIH, Rockville, MD USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Clark, RA (reprint author), Louisiana State Univ, Hlth Sci Ctr, HIV Outpatient Program, 136 S Roman St, New Orleans, LA 70112 USA. FU NCRR NIH HHS [RR-00083] NR 15 TC 58 Z9 60 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2001 VL 184 IS 10 BP 1325 EP 1327 DI 10.1086/323999 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 487NZ UT WOS:000171883300014 PM 11679923 ER PT J AU McFarland, EJ Borkowsky, W Fenton, T Wara, D McNamara, J Samson, P Kang, MH Mofenson, L Cunningham, C Duliege, AM Sinangil, F Spector, SA Jimenez, E Bryson, Y Burchett, S Frenkel, LM Yogev, R Gigliotti, F Luzuriaga, K Livingston, RA AF McFarland, EJ Borkowsky, W Fenton, T Wara, D McNamara, J Samson, P Kang, MH Mofenson, L Cunningham, C Duliege, AM Sinangil, F Spector, SA Jimenez, E Bryson, Y Burchett, S Frenkel, LM Yogev, R Gigliotti, F Luzuriaga, K Livingston, RA CA AIDS Clin Trial Grp 230 Collaborat TI Human immunodeficiency virus type 1 (HIV-1) gp120-specific antibodies in neonates receiving an HIV-1 recombinant gp120 vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th Conference on Retroviruses and Opportunistic Infections CY FEB 01-05, 1998 CL CHICAGO, ILLINOIS ID IMMUNE-RESPONSES; TRANSMISSION; VOLUNTEERS; ENVELOPE; INFANTS; TRIAL; IMMUNOGENICITY; ZIDOVUDINE; INFECTION; ADULTS AB Infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers were immunized at birth and at ages 4, 12, and 20 weeks with low-, medium-, or high-dose recombinant gp120 vaccine with MF59 adjuvant (HIV-1(SF-2); n = 52) or with MF59 alone as a placebo (n = 9). An accelerated schedule (birth and ages 2, 8, and 20 weeks) was used for an additional 10 infants receiving the defined optimal dose and for 3 infants receiving placebo. At 24 weeks, anti-gp120 ELISA titers were greater for vaccine-immunized than for placebo-immunized infants on both schedules, and 87% of vaccinees had a vaccine-induced antibody response. At 12 weeks, antibody titers of infants on the accelerated vaccine schedule exceeded those of infants receiving placebo (4949 vs. 551; P = .01), and 63% of the vaccinees met the response criteria. Thus, an accelerated schedule of gp120 vaccinations generated an antibody response to HIV-1 envelope distinct from transplacental maternal antibody by age 12 weeks. These results provide support for further studies of vaccine strategies to prevent mother-to-infant HIV-1 transmission. C1 Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. NYU, Sch Med, Dept Pediat, New York, NY USA. Syracuse Univ, Dept Pediat, Syracuse, NY USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. Chiron Corp, San Francisco, CA USA. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. NICHHD, NIH, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. San Juan City Hosp, Dept Pediat, San Juan, PR USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. RP McFarland, EJ (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pediat, Box C227,4200 E 9th Ave, Denver, CO 80262 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 15 TC 42 Z9 46 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2001 VL 184 IS 10 BP 1331 EP 1335 DI 10.1086/323994 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 487NZ UT WOS:000171883300016 PM 11679925 ER PT J AU Ma, L Imamichi, H Sukura, A Kovacs, JA AF Ma, L Imamichi, H Sukura, A Kovacs, JA TI Genetic divergence of the dihydrofolate reductase and dihydropteroate synthase genes in Pneumocystis carinii from 7 different host species SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 101st General Meeting of the American-Society-for-Microbiology CY MAY, 2001 CL ORLANDO, FLORIDA SP Ameri Soc Microbiol ID HYDROXYMETHYLDIHYDROPTERIN PYROPHOSPHOKINASE; MUTATIONS; RESISTANCE; EXPRESSION AB To investigate the phylogenetic and therapeutic implications of the genetic divergence in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes among different Pneumocystis carinii strains, these 2 genes in P. carinii obtained from 7 different host species were sequenced. Pairwise comparison of the DHPS sequences demonstrated 6%-24% and 6%-30% divergence in the nucleotide and deduced amino acid sequences, respectively. The DHFR gene was even more divergent, with differences of 15%-34% and 18%-42% in the nucleotide and deduced amino acid sequences, respectively. Phylogenetic analysis of DHFR and DHPS sequences revealed that all P. carinii strains were confined within a distinct group that was closely related to ascomycete fungi and that human-derived P. carinii was most closely related to monkey-derived P. carinii. Recognizing the substantial differences in the DHFR and DHPS genes among P. carinii from different host species has important implications for drug discovery and the development of new diagnostic methods. C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. Univ Helsinki, Fac Vet Med, Dept Vet Basic Sci, Helsinki, Finland. RP Ma, L (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. OI Sukura, Antti Kalle Kalervo/0000-0002-8992-1695 FU NCI NIH HHS [CO-5600] NR 15 TC 24 Z9 26 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2001 VL 184 IS 10 BP 1358 EP 1362 DI 10.1086/324208 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 487NZ UT WOS:000171883300022 PM 11679931 ER PT J AU Kuzhikandathil, EV Wang, HB Szabo, T Morozova, N Blumberg, PM Oxford, GS AF Kuzhikandathil, EV Wang, HB Szabo, T Morozova, N Blumberg, PM Oxford, GS TI Functional analysis of capsaicin receptor (vanilloid receptor subtype 1) multimerization and agonist responsiveness using a dominant negative mutation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE capsaicin; dominant negative; VR1; pain; resiniferatoxin; mutation; CHO cell ID ROOT GANGLION NEURONS; K+ CHANNEL; BINDING; HEAT; DESENSITIZATION; CALCIUM; REGION; ACID; VR1 AB The recently cloned vanilloid receptor subtype 1 (VR1) is a ligand-gated channel that is activated by capsaicin, protons, and heat. We have attempted to develop a dominant negative isoform by targeting several mutations of VR1 at highly conserved amino acids or at residues of potential functional importance and expressing the mutants in Chinese hamster ovary cells. Mutation of three highly conserved amino acid residues in the putative sixth transmembrane domain disrupts activation of the VR1 receptor by both capsaicin and resiniferatoxin. The vanilloid binding site in this mutant is intact, although the affinity for [H-3] resiniferatoxin (RTX) is diminished by nearly 40-fold. Interestingly, this mutant retains a significant but diminished response to protons, supporting the existence of multiple gating mechanisms for different stimuli. The mutant appears to function by interfering with the gating induced by vanilloids rather than the expression level or permeability of the receptor. In addition, this mutant was found to function as a strong dominant negative mutation when coexpressed with wild-type VR1, providing functional evidence that the VR1 receptor forms a multimeric complex. Analysis of both current density and [H-3] RTX affinity in cells cotransfected with different ratios of wild-type and mutant VR1 is consistent with tetrameric stoichiometry for the native capsaicin receptor. C1 Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. NCI, Bethesda, MD 20892 USA. RP Oxford, GS (reprint author), Univ N Carolina, Dept Cell & Mol Physiol, Box 7545,452 Med Sci Res Bldg, Chapel Hill, NC 27599 USA. RI Kuzhikandathil, Eldo/B-1278-2009 FU NINDS NIH HHS [NS18788, NS39420] NR 23 TC 92 Z9 96 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 2001 VL 21 IS 22 BP 8697 EP 8706 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 489VG UT WOS:000172012700003 PM 11698581 ER PT J AU Hammond, V Howell, B Godinho, L Tan, SS AF Hammond, V Howell, B Godinho, L Tan, SS TI disabled-1 functions cell autonomously during radial migration and cortical layering of pyramidal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE disabled-1; Reelin; development; cortex; Emx-1; radial migration ID MOUSE-BRAIN DEVELOPMENT; CEREBRAL-CORTEX; LAMINAR ORGANIZATION; MUTANT MICE; TYROSINE PHOSPHORYLATION; VISUAL-CORTEX; VLDL RECEPTOR; REELER MOUSE; NEOCORTEX; PROTEINS AB Genetic mosaics offer an excellent opportunity to analyze complex gene functions. Chimeras consisting of mutant and wildtype cells provide not only the avenue for lineage-specific gene rescue but can also distinguish cell-autonomous from non-cell-autonomous gene functions. Using an independent genetic marker for wild-type cells, we constructed Dab1(+/+) <->Dab1(-/-) chimeras with the aim of discovering whether or not the function of Dab1 during neuronal migration and cortical layering is cell autonomous. Dab1(+/+) cells were capable of radial migration and columnar formation in a Dab1(-/-) environment. Most Dab1(+/+) cells segregated to the superficial part of the mutant cortex, forming a multilayered supercortex. Neuronal birth-dating studies indicate that supercortex neurons were correctly layered, although adjacent mutant cortex neurons were in reversed order. Immunocytochemistry using Emx1, a marker for pyramidal neurons, indicates that the vast majority of Dab1(+/+) neurons in the supercortex were Emx1 immunoreactive. Confirmation of the pyramidal phenotype was demonstrated by the absence of GABA immunoreactivity among Dab1(+/+) cells in the supercortex. Myelin staining using 2'3'-cyclic nucleotide 3'-phosphodiesterase showed the supercortex was supported by a secondary white matter from which thick fiber tracts appear connected to the underlying mutant white matter. The presence of Dab1(+/+) cells failed to rescue inversion of cortical layers and the abnormal infiltration of the marginal zone by Dab1(+/+) cells. Conversely, mutant cells did not impose a mutant phenotype on adjacent wild-type neurons. These results suggest that Dab1 functions cell autonomously with respect to radial migration and cortical layering of pyramidal neurons. C1 Univ Melbourne, Howard Florey Inst Expt Physiol & Med, Dev Neurobiol Lab, Parkville, Vic 3010, Australia. NINCDS, NIH, Bethesda, MD 20892 USA. RP Tan, SS (reprint author), Univ Melbourne, Howard Florey Inst Expt Physiol & Med, Dev Neurobiol Lab, Parkville, Vic 3010, Australia. OI Howell, Brian/0000-0002-0204-0773 NR 50 TC 35 Z9 38 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 2001 VL 21 IS 22 BP 8798 EP 8808 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 489VG UT WOS:000172012700014 PM 11698592 ER PT J AU Schinelli, S Zanassi, P Paolillo, M Wang, H Feliciello, A Gallo, V AF Schinelli, S Zanassi, P Paolillo, M Wang, H Feliciello, A Gallo, V TI Stimulation of endothelin B receptors in astrocytes induces cAMP response element-binding protein phosphorylation and c-fos expression via multiple mitogen-activated protein kinase signaling pathways SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glia; Rap1; Elk-1; protein kinase C; Raf kinase; ribosomal S6 kinase ID NERVE GROWTH-FACTOR; MAP KINASE; REGULATED KINASE; HEMATOGENOUS METASTASES; COUPLED RECEPTORS; GLIOMA-CELLS; HUMAN BRAIN; RAP1; CREB; RAF AB The vasoconstrictor peptide endothelin (ET-1) exerts its physiological and pathological effects via activation of ETA and ETB receptor (ET-R) subtypes. In this study, we demonstrate that both ET-R subtypes are highly expressed in rat astrocytes in vivo, indicating that these cells are potential targets of the biological effects of ET-1 in the brain. In cultured cortical astrocytes, both ET-R subtypes are expressed, and selective stimulation of ETB-R with ET-1 induces phosphorylation of cAMP response element-binding protein (CREB). The signal transduction pathway activated by ET-1 includes the Rap1/B-Raf and the Ras/Raf-1 complexes, protein kinase C (PKC) together with extracellular signal-regulated kinases (ERK), and the ribosomal S6 kinase (RSK) isoforms RSK2 and RSK3, two kinases that lie immediately downstream of ERK and are able to phosphorylate CREB. Moreover, ET-1 activates the p38 mitogen-activated protein kinase (MAPK)-dependent, but not the c-jun N-terminal kinase (JNK)-dependent pathway. By using selective protein kinase inhibitors and expression of dominant-negative Rap1 protein, we also found that the Rap1/PKC/ERK-dependent pathway induces the phosphorylation of activating transcription factor-1, CREB, and Elk-1, whereas the p38MAPK-dependent pathway only causes CREB phosphorylation. ET-1-induced transcription of the immediate early gene c-fos requires the concomitant activation of both the PKC/ERK- and p38MAPK-dependent pathways, because inhibitors of either pathway block the ET-1-induced increase of c-fos mRNA. Our findings indicate that changes in the expression of cAMP response element-dependent immediate and delayed response genes could play a pivotal role in the physiological effects elicited by ET-1 in astrocytes. C1 NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. Univ Pavia, Fac Farm, Dipartimento Farmacol Sperimentale & Applicata, I-27100 Pavia, Italy. CNR, Dipartimento Biol & Patol Cellulare & Mol, I-80131 Naples, Italy. RP Gallo, V (reprint author), NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bldg 49,Room 5A-78, Bethesda, MD 20892 USA. RI Paolillo, Mayra/N-2615-2015; OI Paolillo, Mayra/0000-0002-7751-3336; Feliciello, Antonio/0000-0002-7932-2170 NR 52 TC 79 Z9 83 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 2001 VL 21 IS 22 BP 8842 EP 8853 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 489VG UT WOS:000172012700018 PM 11698596 ER PT J AU Tabak, J Rinzel, J O'Donovan, MJ AF Tabak, J Rinzel, J O'Donovan, MJ TI The role of activity-dependent network depression in the expression and self-regulation of spontaneous activity in the developing spinal cord SO JOURNAL OF NEUROSCIENCE LA English DT Article DE spontaneous activity; activity-dependent depression; network plasticity; homeostasis; spinal cord; chick embryo ID PATTERNED ELECTRICAL-ACTIVITY; CHICK-EMBRYO; SYNAPTIC TRANSMISSION; STATISTICAL-ANALYSIS; GANGLION-CELLS; RETINAL WAVES; IN-VITRO; NEURONS; OSCILLATIONS; HIPPOCAMPUS AB Spontaneous episodic activity occurs throughout the developing nervous system because immature circuits are hyperexcitable. It is not fully understood how the temporal pattern of this activity is regulated. Here, we study the role of activity-dependent depression of network excitability in the generation and regulation of spontaneous activity in the embryonic chick spinal cord. We demonstrate that the duration of an episode of activity depends on the network excitability at the beginning of the episode. We found a positive correlation between episode duration and the preceding inter-episode interval, but not with the following interval, suggesting that episode onset is stochastic whereas episode termination occurs deterministically, when network excitability falls to a fixed level. This is true over a wide range of developmental stages and under blockade of glutamatergic or GABAergic/glycinergic synapses. We also demonstrate that during glutamatergic blockade the remaining part of the network becomes more excitable, compensating for the loss of glutamatergic synapses and allowing spontaneous activity to recover. This compensatory increase in the excitability of the remaining network reflects the progressive increase in synaptic efficacy that occurs in the absence of activity. Therefore, the mechanism responsible for the episodic nature of the activity automatically renders this activity robust to network disruptions. The results are presented using the framework of our computational model of spontaneous activity in the developing cord. Specifically, we show how they follow logically from a bistable network with a slow activity-dependent depression switching periodically between the active and inactive states. C1 NINCDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. NYU, Courant Inst Math Sci, New York, NY 10003 USA. RP Tabak, J (reprint author), NINCDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RI tabak, joel/K-1549-2013; o'donovan, michael/A-2357-2015 OI o'donovan, michael/0000-0003-2487-7547 NR 35 TC 74 Z9 74 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 2001 VL 21 IS 22 BP 8966 EP 8978 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 489VG UT WOS:000172012700029 PM 11698607 ER PT J AU Topol, IA Nemukhin, AV Dobrogorskaya, YI Burt, SK AF Topol, IA Nemukhin, AV Dobrogorskaya, YI Burt, SK TI Interactions of azodicarbonamide (ADA) species with the model zinc finger site: Theoretical support of the zinc finger domain destruction in the HIV-1 nucleocapsid protein (NCp7) by ADA SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID DENSITY-FUNCTIONAL THEORY; INHIBITORS; REPLICATION; EJECTION; ATOMS AB Interactions of azodicarbonamide (ADA) species with zinc-containing sites, which mimic the zinc finger domains of the HIV-1 nucleocapsid protein (NCp7), have been investigated by quantum chemistry tools in order to provide theoretical insights into recent experimental findings. In the latter, reactions of ADA with NCp7 lead to destabilization of the zinc coordination sphere followed by HIV inhibition. In this work, energy profiles for the interactions of neutral and protonated ADA species with the Zn binding site have been calculated at the density functional theory level in the B3LYP approximation. The calculations show that the ADA molecule, protonated at the central nitrogen atom, reacts without activation barrier with the model zinc binding site, destructing the metal coordination sphere, while interactions of other ADA species do not lead to modification of the metal site. C1 NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119899, Russia. RP Topol, IA (reprint author), NCI, Adv Biomed Comp Ctr, SAIC Frederick, POB B, Frederick, MD 21702 USA. RI Nemukhin, Alexander/P-9662-2015 NR 31 TC 15 Z9 17 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD NOV 15 PY 2001 VL 105 IS 45 BP 11341 EP 11350 DI 10.1021/jp011734g PG 10 WC Chemistry, Physical SC Chemistry GA 493DG UT WOS:000172206300036 ER PT J AU Il'ichev, YV Perry, JL Manderville, RA Chignell, CF Simon, JD AF Il'ichev, YV Perry, JL Manderville, RA Chignell, CF Simon, JD TI The pH-Dependent primary photoreactions of Ochratoxin A SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID INTRAMOLECULAR PROTON-TRANSFER; PSORALEN RADICAL CATIONS; DNA ADDUCT FORMATION; NM LASER-LIGHT; AQUEOUS-SOLUTION; REDOX CHEMISTRY; PHOTOLYSIS; 4-CHLOROPHENOL; CHLORPROMAZINE; ELECTRON AB Steady-state and time-resolved spectroscopies are used to elucidate the primary photoprocesses following the excitation of ochratoxin A (OTA), its dechlorinated derivative ochratoxin B (OTB), and O-methyl ether of OTA (MOA). The excited-state dynamics of OTA and OTB depend on the protonation of the isocoumarin moiety. Fluorescence spectra of the protonated forms reveal anomalously large Stokes shifts that are attributed to the enol tautomer formed via an intramolecular excited-state proton transfer. No evidence for "normal" emission of the keto form of OTA and OTB is found even in aqueous solutions. MOA, which lacks a proton on the phenol moiety and exists, therefore, only in the keto form, exhibits weak fluorescence with a substantially smaller Stokes shift. The deprotonated species show relatively strong emission typical for phenolate anions. OTA decomposes slowly upon UV irradiation in aqueous solutions. The photoreaction quantum yield varies significantly with solution pH and O-2 concentration. The highest yield is observed for the deprotonated form of OTA in deoxygenated solutions. The corresponding hydroquinone (OHQ) is identified as a major photoproduct. Monophotonic photoionization of the fully deprotonated OTA in aqueous solution is demonstrated with nanosecond laser flash photolysis. In the absence of O-2 and other scavengers, hydrated electrons are trapped by OTA in the ground state with the diffusion-controlled rate constant. Photoirradiation of OTA in the presence of supercoiled plasmid DNA results in the formation of relaxed circular DNA (form II). The yield of form II correlates with the quantum yield of OTA photodecompositon in these solutions, because the photocleavage efficiency is higher in the absence Of O-2 and at basic pH. C1 Duke Univ, Dept Chem, Durham, NC 27708 USA. Wake Forest Univ, Dept Chem, Winston Salem, NC 27109 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Simon, JD (reprint author), Duke Univ, Dept Chem, Durham, NC 27708 USA. NR 81 TC 29 Z9 29 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD NOV 15 PY 2001 VL 105 IS 45 BP 11369 EP 11376 DI 10.1021/jp012683q PG 8 WC Chemistry, Physical SC Chemistry GA 493DG UT WOS:000172206300039 ER PT J AU Cornog, M Plantz, EJ AF Cornog, M Plantz, EJ TI A misunderstood faith SO LIBRARY JOURNAL LA English DT Editorial Material C1 Natl Lib Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD NOV 15 PY 2001 VL 126 IS 19 BP 82 EP 82 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 494KA UT WOS:000172280200158 ER PT J AU Rose, EA Gelijns, AC Moskowitz, AJ Heitjan, DF Stevenson, LW Dembitsky, W Long, JW Ascheim, DD Tierney, AR Levitan, RG Watson, JT Meier, P AF Rose, EA Gelijns, AC Moskowitz, AJ Heitjan, DF Stevenson, LW Dembitsky, W Long, JW Ascheim, DD Tierney, AR Levitan, RG Watson, JT Meier, P CA Randomized Evaluation Mech Assista TI Long-term use of a left ventricular assist device for end-stage heart failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CARDIAC TRANSPLANTATION; CONTROLLED TRIAL; MENTAL-HEALTH; EXPERIENCE; MORTALITY; VALIDITY; BRIDGE; DESIGN AB Background: Implantable left ventricular assist devices have benefited patients with end-stage heart failure as a bridge to cardiac transplantation, but their long-term use for the purpose of enhancing survival and the quality of life has not been evaluated. Methods: We randomly assigned 129 patients with end-stage heart failure who were ineligible for cardiac transplantation to receive a left ventricular assist device (68 patients) or optimal medical management (61). All patients had symptoms of New York Heart Association class IV heart failure. Results: Kaplan-Meier survival analysis showed a reduction of 48 percent in the risk of death from any cause in the group that received left ventricular assist devices as compared with the medical-therapy group (relative risk, 0.52; 95 percent confidence interval, 0.34 to 0.78; P=0.001). The rates of survival at one year were 52 percent in the device group and 25 percent in the medical-therapy group (P=0.002), and the rates at two years were 23 percent and 8 percent (P=0.09), respectively. The frequency of serious adverse events in the device group was 2.35 (95 percent confidence interval, 1.86 to 2.95) times that in the medical-therapy group, with a predominance of infection, bleeding, and malfunction of the device. The quality of life was significantly improved at one year in the device group. Conclusions: The use of a left ventricular assist device in patients with advanced heart failure resulted in a clinically meaningful survival benefit and an improved quality of life. A left ventricular assist device is an acceptable alternative therapy in selected patients who are not candidates for cardiac transplantation. C1 Columbia Univ, Coll Phys & Surg, New York, NY USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, New York, NY USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA. LDS Hosp, Salt Lake City, UT USA. NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Texas Heart Inst, Houston, TX 77025 USA. Thoratec Corp, Pleasanton, CA USA. RP Rose, EA (reprint author), Columbia Univ, Int Ctr Hlth Outcomes & Innovat, 600 W 168th St,7th Fl, New York, NY 10032 USA. RI Heitjan, Daniel/D-1116-2009; OI Moskowitz, Alan/0000-0002-4412-9450 FU NHLBI NIH HHS [HL-53986] NR 33 TC 1806 Z9 1856 U1 2 U2 56 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 15 PY 2001 VL 345 IS 20 BP 1435 EP 1443 DI 10.1056/NEJMoa012175 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 491WH UT WOS:000172132700001 PM 11794191 ER PT J AU Hoofnagle, JH AF Hoofnagle, JH TI Therapy for acute hepatitis C SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID VIRUS-INFECTION; UNITED-STATES; PREVALENCE C1 NIDDKD, Bethesda, MD 20817 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Bethesda, MD 20817 USA. NR 15 TC 26 Z9 27 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 15 PY 2001 VL 345 IS 20 BP 1495 EP 1497 DI 10.1056/NEJM200111153452013 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 491WH UT WOS:000172132700012 PM 11794202 ER PT J AU Kreitman, RJ Wilson, WH Pastan, I AF Kreitman, RJ Wilson, WH Pastan, I TI Treatment of hairy-cell leukemia - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID TERM FOLLOW-UP; CLADRIBINE C1 NCI, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 15 PY 2001 VL 345 IS 20 BP 1500 EP 1501 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 491WH UT WOS:000172132700019 ER PT J AU Boudsocq, F Iwai, S Hanaoka, F Woodgate, R AF Boudsocq, F Iwai, S Hanaoka, F Woodgate, R TI Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4): an archaeal DinB-like DNA polymerase with lesion-bypass properties akin to eukaryotic pol eta SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SINGLE-STRANDED-DNA; ESCHERICHIA-COLI; XERODERMA-PIGMENTOSUM; GENE ENCODES; MOUSE HOMOLOGS; THYMINE DIMER; LOW-FIDELITY; MUTAGENESIS; PROTEIN; ALIGNMENT AB Phylogenetic analysis of Y-family DNA polymerases suggests that it can be subdivided into several: discrete branches consisting of UmuC/DinB/Rev1/Rad30/Rad30A and Rad30B. The most diverse is the DinB family that is found in all three kingdoms of life. Searches of the complete genome of the crenarchaeon Sulfolobus solfataricus P2 reveal that it possesses a DinB homolog that has been termed DNA polymerase IV (Dpo4). We have overproduced and purified native Dpo4 protein and report here its enzymatic characterization. Dpo4 is thermostable, but can also synthesize DNA at 37 degreesC. Under these conditions, the enzyme exhibits misinsertion fidelities in the range of 8 x 10(-3) to 3 x 10(-4). Dpo4 is distributive but at high enzyme to template ratios can synthesize long stretches of DNA and can substitute for Taq polymerase in PCR. On damaged DNA templates, Dpo4 can facilitate translesion replication of an abasic site, a cis-syn thymine-thymine dimer, as well as acetyl aminofluorene adducted- and cisplatinated-guanine residues. Thus, although phylogenetically, related to DinB polymerases, our studies suggest that the archaeal Dpo4 enzyme exhibits lesion-bypass properties that are, in fact, more akin to those of eukaryotic pol eta. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. Biomol Engn Res Inst, Osaka 5650874, Japan. Osaka Univ, Inst Mol & Cellular Biol, Suita, Osaka 5650871, Japan. Japan Sci & Technol Corp, CREST, Suita, Osaka 5650871, Japan. RIKEN, Inst Phys & Chem Res, Wako, Saitama 3510198, Japan. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. NR 52 TC 149 Z9 151 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 2001 VL 29 IS 22 BP 4607 EP 4616 DI 10.1093/nar/29.22.4607 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496CK UT WOS:000172378000011 PM 11713310 ER PT J AU Atha, DH Kasprzak, W O'Connell, CD Shapiro, BA AF Atha, DH Kasprzak, W O'Connell, CD Shapiro, BA TI Prediction of DNA single-strand conformation polymorphism: analysis by capillary electrophoresis and computerized DNA modeling SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA STRUCTURE-ANALYSIS; SECONDARY STRUCTURE; MUTATIONS AB We have analyzed previously three representative p53 single-point mutations by capillary-electrophoresis single-strand conformation polymorphism (CE-SSCP). In the current study, we compared our CE-SSCP results with the potential secondary structures predicted by an RNA/DNA-folding algorithm with DNA, energy rules, used in conjunction with a computer analysis workbench called STRUCTURELAB. Each of these mutations produces measurable shifts in CE migration times relative to wild type. Using computerized folding analysis, each of the mutations was found to have a conformational difference relative to wild type, which accounts for the observed differences in CE migration. Additional properties exhibited in the CE electropherograms were also explained using the computerized analysis. These include the appearance of secondary peaks and the temperature dependence of the electrophoretic patterns. The results yield insight into the mechanism of SSCP and how the conditions of this measurement, especially temperature, may be optimized to improve the sensitivity of the SSCP method. The results may also impact other diagnostic methods, which would benefit by a better understanding of DNA single-strand conformation polymorphisms to optimize conditions for enzymatic cleavage and DNA hybridization reactions. C1 NIST, Div Biotechnol, Gaithersburg, MD 20899 USA. NCI, Canc Res Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. NCI, IRSP, SAIC Frederick, Frederick, MD 21702 USA. RP Atha, DH (reprint author), NIST, Div Biotechnol, Bldg 227,Room A-243, Gaithersburg, MD 20899 USA. FU NCI NIH HHS [N01-CO-56000] NR 14 TC 22 Z9 25 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 2001 VL 29 IS 22 BP 4643 EP 4653 DI 10.1093/nar/29.22.4643 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496CK UT WOS:000172378000015 PM 11713314 ER PT J AU Elmendorf, HG Singer, SM Nash, TE AF Elmendorf, HG Singer, SM Nash, TE TI The abundance of sterile transcripts in Giardia lamblia SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NATURAL ANTISENSE TRANSCRIPTS; PRIMITIVE EUKARYOTE; GLUTAMATE-DEHYDROGENASE; PHYLOGENETIC PLACE; LACKING PROTOZOAN; GENE PROMOTER; RNA; EXPRESSION; PROTEIN; IDENTIFICATION AB The protozoan parasite Giardia lamblia synthesizes a diverse and surprisingly abundant array of sterile transcripts unable to code for proteins. Random sampling of cDNAs from two evolutionarily divergent Giardia strains indicates that similar to 20% of cDNAs in the libraries represent polyadenylated sterile transcripts. RNase protection analysis and northern blot hybridization of three sterile transcript loci demonstrated that both the sterile transcript and a complementary mRNA were made in each case, further categorizing these sterile transcripts as antisense transcripts. Investigation of the genomic loci for these same three sterile antisense transcripts showed typical transcription units for the sense transcripts, but still failed to reveal a usable open reading frame for the sterile antisense transcripts. 5'-RACE mapped the transcription start site for one of the sterile antisense transcripts to an AT-rich region, as is typical for Giardia. It is unclear whether these sterile transcripts represent errors in transcription or whether they have regulatory functions within the cell, although preliminary investigations failed to reveal evidence for a role in developmental gene regulation. In either case, the presence of such a large pool of sterile antisense transcripts is dramatic evidence of the unusual molecular machinery of the early diverging protist G. Iamblia. C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Elmendorf, HG (reprint author), Georgetown Univ, Dept Biol, 306A Reiss Bldg,37th & O St NW, Washington, DC 20057 USA. NR 54 TC 50 Z9 52 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 15 PY 2001 VL 29 IS 22 BP 4674 EP 4683 DI 10.1093/nar/29.22.4674 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496CK UT WOS:000172378000018 PM 11713317 ER PT J AU Sonnhammer, ELL Wootton, JC AF Sonnhammer, ELL Wootton, JC TI Integrated graphical analysis of protein sequence features predicted from sequence composition SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE sequence analysis; graphical visualization; dot-plot; database search viewing; sequence complexity; transmembrane; coiled-coil; protein structure; nonglobular proteins; algorithms; data definition format ID TOPOLOGY PREDICTION; MEMBRANE-PROTEINS; DATABASES; COMPLEXITY; DNA AB Several protein sequence analysis algorithms are based on properties of amino acid composition and repetitiveness. These include methods for prediction of secondary structure elements, coiled-coils, transmembrane segments or signal peptides, and for assignment of low-complexity, nonglobular, or intrinsically unstructured regions. The quality of such analyses can be greatly enhanced by graphical software tools that present predicted sequence features together in context and allow judgment to be focused simultaneously on several different types of supporting information. For these purposes, we describe the SFINX package, which allows many different sets of segmental or continuous-curve sequence feature data, generated by individual external programs, to be viewed in combination alongside a sequence dot-plot or a multiple alignment of database matches. The implementation is currently based on extensions to the graphical viewers Dotter and Blixem and scripts that convert data from external programs to a simple generic data definition format called SFS. We describe applications in which dot-plots and flanking database matches provide valuable contextual information for analyses based on compositional and repetitive sequence features. The system is also useful for comparing results from algorithms run with a range of parameters to determine appropriate values for defaults or cutoffs for large-scale genomic analyses. (C) 2001 Wiley-Liss, Inc. C1 Karolinska Inst, Ctr Genomics & Bioinformat, S-17177 Stockholm, Sweden. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Sonnhammer, ELL (reprint author), Karolinska Inst, Ctr Genomics & Bioinformat, S-17177 Stockholm, Sweden. NR 33 TC 31 Z9 32 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 15 PY 2001 VL 45 IS 3 BP 262 EP 273 DI 10.1002/prot.1146 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 484PY UT WOS:000171699800011 PM 11599029 ER PT J AU Elster, EA Xu, H Tadaki, DK Montgomery, S Burkly, LC Berning, JD Baumgartner, RE Cruzata, F Marx, R Harlan, DM Kirk, AD AF Elster, EA Xu, H Tadaki, DK Montgomery, S Burkly, LC Berning, JD Baumgartner, RE Cruzata, F Marx, R Harlan, DM Kirk, AD TI Treatment with the humanized CD154-specific monoclonal antibody, hu5C8, prevents acute rejection of primary skin allografts in nonhuman primates SO TRANSPLANTATION LA English DT Article ID LONG-TERM SURVIVAL; INTRAHEPATIC ISLET ALLOGRAFTS; T-CELLS; ANTI-CD154 ANTIBODY; CD40; TOLERANCE; BLOCKING; PATHWAYS; LEADS; GAMMA AB Background. Allogeneic skin transplantation remains a rigorous test of any immune intervention designed to prevent allograft rejection. To date, no single, clinically available immunosuppressant has been reported to induce long-term primary skin allograft survival in primates. We have previously shown that treatment with the humanized CD154-specific monoclonal antibody, humanized 5C8 (hu5C8), induces long-term renal allograft survival in nonhuman primates. In this study, we evaluated the efficacy of hu5C8 in preventing primary skin allograft rejection in rhesus monkeys. Methods. Ten rhesus monkeys were transplanted with full-thickness skin allografts mismatched at both class I and class II major histocompatibility loci. Of these, two were given no treatment, five were treated with hu5C8 alone, and three received hu5C8 combined with whole blood donor-specific transfusion (DST). All recipients also received skin autografts for comparison. Animals were followed by inspection, serial biopsy, mixed lymphocyte culture, and alloantibody determination. Results. Treatment with hu5C8 alone or hu5C8 plus DST greatly prolonged allograft survival. Rejection occurred in the untreated group within 7 days. Mean allograft survival in the monotherapy hu5C8 group was > 236 days and in the DST group was > 202 days; these differences were not significant. Rejection eventually occurred in most animals. Allograft survival was not correlated with the development of T cell hyporesponsiveness in mixed lymphocyte culture. Rejection was not predicted by the development of donor-specific alloantibody. Conclusion. These results show that treatment with the CD154-specific monoclonal antibody, hu5C8, greatly delays the onset of acute skin allograft rejection. C1 NIDDK, USN, Transplantat & Autoimmun Branch, Bethesda, MD 20889 USA. Natl Naval Med Res Inst, Dept Gen Surg, Bethesda, MD 20889 USA. Biogen Inc, Cambridge, MA 02142 USA. RP Kirk, AD (reprint author), NIH, Bldg 10,Ctr Dr,Room 11S-219, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 FU NIAID NIH HHS [AI43900-01] NR 21 TC 66 Z9 67 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2001 VL 72 IS 9 BP 1473 EP 1478 DI 10.1097/00007890-200111150-00001 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 497QZ UT WOS:000172468100001 PM 11707732 ER PT J AU Liotta, LA Kohn, EC Petricoin, EF AF Liotta, LA Kohn, EC Petricoin, EF TI Clinical proteomics - Personalized molecular medicine SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID IMMOBILIZED PH GRADIENTS; 2-DIMENSIONAL ELECTROPHORESIS; QUANTITATIVE-ANALYSIS; PROTEIN; CANCER; COMPLEXES C1 NCI, CCR, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Liotta, LA (reprint author), 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. NR 25 TC 162 Z9 173 U1 1 U2 26 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 14 PY 2001 VL 286 IS 18 BP 2211 EP 2214 DI 10.1001/jama.286.18.2211 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 491VA UT WOS:000172129700001 PM 11710876 ER PT J AU King, MC Wieand, S Hale, K Lee, M Walsh, T Owens, K Tait, J Ford, L Dunn, BK Costantino, J Wickerham, L Wolmark, N Fisher, B AF King, MC Wieand, S Hale, K Lee, M Walsh, T Owens, K Tait, J Ford, L Dunn, BK Costantino, J Wickerham, L Wolmark, N Fisher, B TI Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2 - National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ASHKENAZI JEWISH WOMEN; OVARIAN-CANCER; GENE-MUTATIONS; CARRIERS; RISK; PROBABILITIES; CARCINOMAS; PREVALENCE; FREQUENCY; SEQUENCE AB Context Among cancer-free women aged 35 years or older, tamoxifen reduced the incidence of estrogen receptor (ER)-positive but not ER-negative breast cancer. The effect of tamoxifen on breast cancer incidence among women at extremely high risk due to inherited BRCA1 or BRCA2 mutations is unknown. Objective To evaluate the effect of tamoxifen on incidence of breast cancer among cancer-free women with inherited BRCA1 or BRCA2 mutations. Design, Setting, and Participants Genomic analysis of BRCA1 and BRCA2 for 288 women who developed breast cancer after entry into the randomized, double-blind Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel Project (between April 1, 1992, and September 30, 1999). Main Outcome Measure Among women with BRCA1 or BRCA2 mutations, incidence of breast cancer among those who were receiving tamoxifen vs incidence of breast cancer among those receiving placebo. Results Of the 288 breast cancer cases, 19 (6.6%) inherited disease-predisposing BRCA1,or BRCA2 mutations. Of 8 patients with BRCA1 mutations, 5 received tamoxifen and 3 received placebo (risk ratio, 1.67; 95% confidence interval, 0.32-10.70). Of 11 patients with BRCA2 mutations, 3 received tamoxifen and 8 received placebo (risk ratio, 0.38; 95% confidence interval, 0.06-1.56). From 10 studies, including this one, 83% of BRCA1 breast tumors were ER-negative, whereas 76% of BRCA2 breast tumors were ER-positive. Conclusion Tamoxifen reduced breast cancer incidence among healthy BRCA2 carriers by 62%, similar to the reduction in incidence of ER-positive breast cancer among all women in the Breast Cancer Prevention Trial. In contrast, tamoxifen use beginning at age 35 years or older did not reduce breast cancer incidence among healthy women with inherited BRCA1 mutations. Whether tamoxifen use at a younger age would reduce breast cancer incidence among healthy women with BRCA1 mutations remains unknown. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Genom Sci, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. RP King, MC (reprint author), Univ Washington, Dept Med, POB 357720, Seattle, WA 98195 USA. FU NCI NIH HHS [U10 CA37377, U10 CA69974] NR 39 TC 403 Z9 412 U1 2 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 14 PY 2001 VL 286 IS 18 BP 2251 EP 2256 DI 10.1001/jama.286.18.2251 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 491VA UT WOS:000172129700019 PM 11710890 ER PT J AU Collins, FS Guttmacher, AE AF Collins, FS Guttmacher, AE TI Genetics moves into the medical mainstream SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HUMAN-GENOME-PROJECT; HEALTH-PROFESSIONALS; CANCER; LEUKEMIA; SEQUENCE; FAMILIES; MUTATION; DISEASE; TRIAL; GENES C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA. EM francisc@mail.nih.gov NR 21 TC 57 Z9 59 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 14 PY 2001 VL 286 IS 18 BP 2322 EP 2324 DI 10.1001/jama.286.18.2322 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 491VA UT WOS:000172129700028 PM 11710899 ER PT J AU Camitta, MGW Gabel, SA Chulada, P Bradbury, JA Langenbach, R Zeldin, DC Murphy, E AF Camitta, MGW Gabel, SA Chulada, P Bradbury, JA Langenbach, R Zeldin, DC Murphy, E TI Cyclooxygenase-1 and-2 knockout mice demonstrate increased cardiac ischemia/reperfusion injury but are protected by acute preconditioning SO CIRCULATION LA English DT Article DE ischemia; reperfusion; preconditioning; prostaglandin; cyclooxygenase ID ARACHIDONIC-ACID; RAT-HEART; CARDIOMYOCYTES; APOPTOSIS; SYNTHASE; PRODUCTS AB Background-The purpose of this study was to examine the effects of cyclooxygenase (COX) deficiency on baseline functional characteristics and on recovery of left ventricular developed pressure (LVDP) after 20 minutes of global ischemia and 40 minutes of reperfusion in untreated and preconditioned hearts. Methods and Results-Compared with hearts from wild-type (WT) and COX-2(-/-) mice, baseline cardiac prostaglandin (PG) E-2 and 6-keto-PGF(1 alpha) levels were significantly decreased in hearts from COX-1(-/-) mice. After ischemia, cardiac PGE(2) levels increased in WT, COX-1(-/-), and COX-2(-/-) mice (P <0.05). Recovery of function (LVDP) after global ischemia in hearts from COX-1(-/-) and COX-2(-/-) mice was significantly less than in WT hearts. Pretreatment of WT mice with indomethacin for 2 days before ischemia significantly decreased LVDP recovery; however, perfusion of WT hearts with indomethacin for 40 minutes before ischemia did not significantly alter LVDP recovery, Postischemic recovery of LVDP in COX-1(-/-) and COX-2(-/-) was unchanged by perfusion with 5 mu mol/L PGE(2), PGD(2), PGF(2 alpha), or carboprostacyclin. Hearts from COX-2(-/-) mice showed an increase in ischemic contracture compared with hearts from WT and COX-1(-/-) mice; however, hearts did not differ in intracellular pH, ATP, or inorganic phosphate during ischemia. Ischemic preconditioning significantly improved postischemic LVDP recovery in COX-1(-/-), COX-2(-/-), and WT mice. Conclusions-Genetic disruption or 2-day chemical inhibition of COX-1 and COX-2 decreases recovery of LVDP after ischemia; however, acute perfusion with indomethacin is not detrimental. These data are consistent with protection due to the altered expression of some protein that is modulated by COX or its metabolites. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Div Pediat Cardiol, Durham, NC USA. RP Zeldin, DC (reprint author), NIEHS, NIH, MD D2-01, Res Triangle Pk, NC 27709 USA. NR 20 TC 62 Z9 66 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 13 PY 2001 VL 104 IS 20 BP 2453 EP 2458 DI 10.1161/hc4401.098429 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 494CF UT WOS:000172260600023 PM 11705824 ER PT J AU Jacobs, MP Fischbach, GD Davis, MR Dichter, MA Dingledine, R Lowenstein, DH Morrell, MJ Noebels, JL Rogawski, MA Spencer, SS Theodore, WH AF Jacobs, MP Fischbach, GD Davis, MR Dichter, MA Dingledine, R Lowenstein, DH Morrell, MJ Noebels, JL Rogawski, MA Spencer, SS Theodore, WH TI Future directions for epilepsy research SO NEUROLOGY LA English DT Article ID ELECTRICAL-STIMULATION; GENE-TRANSFER; HEAD-INJURY; SEIZURES; BRAIN; RAT; HIPPOCAMPAL; CHANNEL; MICE; EEG AB The authors propose that epilepsy research embark on a revitalized effort to move from targeting control of symptoms to strategies for prevention and cure. The recent advances that make this a realistic goal include identification of genes mutated in inherited epilepsy syndromes, molecular characterization of brain networks, better imaging of sites of seizure origin, and developments in seizure prediction by quantitative EEG analysis. Research directions include determination of mechanisms of epilepsy development, identification of genes for common epilepsy syndromes through linkage analysis and gene chip technology, and validation of new models of epilepsy and epileptogenesis. Directions for therapeutics include identification of new molecular targets, focal methods of drug delivery tied to EEG activity, gene and cell therapy, and surgical and nonablative therapies. Integrated approaches, such as coupling imaging with electrophysiology, are central to progress in localizing regions of epilepsy development in people at risk and better seizure prediction and treatment for people with epilepsy. C1 NINCDS, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Boston, MA USA. Columbia Presbyterian Med Ctr, Coll Phys & Surg, New York, NY 10032 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. RP Jacobs, MP (reprint author), NINCDS, NIH, Suite 2138,6001 Execut Blvd, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009; dingledine, Ray/F-5173-2011; OI Rogawski, Michael/0000-0002-3296-8193; Noebels, Jeffrey /0000-0002-2887-0839 NR 65 TC 66 Z9 71 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 13 PY 2001 VL 57 IS 9 BP 1536 EP 1542 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 492HA UT WOS:000172161300004 PM 11706087 ER PT J AU Kidwell, CS Saver, JL Mattiello, J Warach, S Liebeskind, DS Starkman, S Vespa, PM Villablanca, JP Martin, NA Frazee, J Alger, JR AF Kidwell, CS Saver, JL Mattiello, J Warach, S Liebeskind, DS Starkman, S Vespa, PM Villablanca, JP Martin, NA Frazee, J Alger, JR TI Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage SO NEUROLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; HIGH-RESOLUTION MEASUREMENT; BRAIN-BARRIER PERMEABILITY; SPONTANEOUS MASS LESION; TRACER BOLUS PASSAGES; WEIGHTED MRI; ISCHEMIC PENUMBRA; EDEMA FORMATION; ACUTE STROKE; SURGERY AB Background: It has been suggested that a zone of perihematomal ischemia analogous to an ischemic penumbra exists in patients with primary intracerebral hemorrhage (ICH). Diffusion-perfusion MRI provides a novel means of assessing injury in perihematomal regions in patients with ICH. Objective: To characterize diffusion-perfusion MRI changes in the perihematomal region in patients with hyperacute intracerebral hemorrhage. Methods: Twelve patients presenting with hyperacute, primary ICH undergoing CT scanning and diffusion-perfusion MRI within 6 hours of symptom onset were reviewed. An automated thresholding technique was used to identify decreased apparent diffusion coefficient (ADC) values in the perihematomal regions. Perfusion maps were examined for regions of relative hypo- or hyperperfusion. Results: Median baseline NIH Stroke Scale score was 17 (range, 6 to 28). Median hematoma volume was 13.3 mL (range, 3.0 to 74.8 mL). MRI detected the hematoma in all patients on echo-planar susceptibility-weighted imaging and in all seven patients imaged with gradient echo sequences. In six patients who underwent perfusion imaging, no focal defects were visualized on perfusion maps in tissues adjacent to the hematoma; however, five of six patients demonstrated diffuse ipsilateral hemispheric hypoperfusion. On diffusion imaging, perihematomal regions of decreased ADC values were identified in three of 12 patients. All three subsequently showed clinical and radiologic deterioration. Conclusions: A rim of perihematomal decreased ADC values was visualized in the hyperacute period in a subset of patients with ICH. The presence of a rim of decreased ADC outside the hematoma correlated with poor clinical outcome. Although perfusion maps did not demonstrate a focal zone of perihematomal decreased blood flow in any patient, most patients had ipsilateral hemispheric hypoperfusion. C1 Univ Calif Los Angeles, Med Ctr, Stroke Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Radiol Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Emergency Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Neurosurg, Los Angeles, CA 90095 USA. NINCDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Comprehens Stroke Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Kidwell, CS (reprint author), Univ Calif Los Angeles, Med Ctr, Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA. OI Martin, Neil/0000-0002-6565-4131; Saver, Jeffrey/0000-0001-9141-2251 FU NINDS NIH HHS [K24 NS 02092-01, K23 NS 02088-01, NS 39496] NR 46 TC 104 Z9 114 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 13 PY 2001 VL 57 IS 9 BP 1611 EP 1617 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 492HA UT WOS:000172161300018 PM 11706101 ER PT J AU Miyoshi, K Shillingford, JM Smith, GH Grimm, SL Wagner, KU Oka, T Rosen, JM Robinson, GW Hennighausen, L AF Miyoshi, K Shillingford, JM Smith, GH Grimm, SL Wagner, KU Oka, T Rosen, JM Robinson, GW Hennighausen, L TI Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium SO JOURNAL OF CELL BIOLOGY LA English DT Article DE prolactin receptor; Stat5; mammary gland; cell specification; epithelia ID GLAND DEVELOPMENT; C/EBP-BETA; FUNCTIONAL-DIFFERENTIATION; LOBULOALVEOLAR DEVELOPMENT; DUCTAL MORPHOGENESIS; TIGHT JUNCTIONS; CELL-ADHESION; MICE LACKING; E-CADHERIN; CYCLIN D1 AB Functional development of mammary epithelium during pregnancy depends on prolactin signaling. However, the underlying molecular and cellular events are not fully understood. We examined the specific contributions of the prolactin receptor (PrIR) and the signal transducers and activators of transcription 5a and 5b (referred to as Stat5) in the formation and differentiation of mammary alveolar epithelium. PrIR- and Stat5-null mammary epithelia were transplanted into wild-type hosts, and pregnancy-mediated development was investigated at a histological and molecular level. Stat5-null mammary epithelium developed ducts but failed to form alveoli, and no milk protein gene expression was observed. In contrast, PrIR-null epithelium formed alveoli-like structures with small open lumina. Electron microscopy revealed undifferentiated features of organelles and a perturbation of cell-cell contacts in PrIR- and Stat5-null epithelia. Expression of NKCC1, an Na-K-Cl cotransporter characteristic for ductal epithelia, and ZO-1, a protein associated with tight junction, were maintained in the alveoli-like structures of PrIR- and Stat5-null epithelia. In contrast, the Na-Pi cotransporter Npt2b, and the gap junction component connexin 32, usually expressed in secretory epithelia, were undetectable in PrIR- and Stat5-null mice. These data demonstrate that signaling via the PrIR and Stat5 is critical for the proliferation and differentiation of mammary alveoli during pregnancy. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. NCI, Lab Tumor Biol, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Univ Nebraska, Med Ctr, Omaha, NE 68198 USA. Univ Tokushima, Sch Dent, Dept Biochem, Tokushima 7708504, Japan. RP Miyoshi, K (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Rm 101, Bethesda, MD 20892 USA. EM mammary@nih.gov RI Wagner, Kay-Uwe/B-6044-2009; Robinson, Gertraud/I-2136-2012 NR 54 TC 193 Z9 197 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 12 PY 2001 VL 155 IS 4 BP 531 EP 542 DI 10.1083/jcb.200107065 PG 12 WC Cell Biology SC Cell Biology GA 494PQ UT WOS:000172291400006 PM 11706048 ER PT J AU Ward, TH Polishchuk, RS Caplan, S Hirschberg, K Lippincott-Schwartz, J AF Ward, TH Polishchuk, RS Caplan, S Hirschberg, K Lippincott-Schwartz, J TI Maintenance of Golgi structure and function depends on the integrity of ER export SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Golgi apparatus; FRAP; GFP; COPII; coatomer ID EARLY SECRETORY PATHWAY; ENDOPLASMIC-RETICULUM; LIVING CELLS; BREFELDIN-A; IN-VIVO; RECYCLING PATHWAY; PROTEIN ERGIC-53; EXIT SITES; COP-I; TRANSPORT AB The Golgi apparatus comprises an enormous array of components that generate its unique architecture and function within cells. Here, we use quantitative fluorescence imaging techniques and ultrastructural analysis to address whether the Golgi apparatus is a steady-state or a stable organelle. We found that all classes of Golgi components are dynamically associated with this organelle, contrary to the prediction of the stable organelle model. Enzymes and recycling components are continuously exiting and reentering the Golgi apparatus by membrane trafficking pathways to and from the ER, whereas Golgi matrix proteins and coatomer undergo constant, rapid exchange between membrane and cytoplasm. When ER to Golgi transport is inhibited without disrupting COPII-dependent ER export machinery (by brefeldin A treatment or expression of Arf1 [T31N]), the Golgi structure disassembles, leaving no residual Golgi membranes. Rather, all Golgi components redistribute into the ER, the cytoplasm, or to ER exit sites still active for recruitment of selective membrane-bound and peripherally associated cargos. A similar phenomenon is induced by the constitutively active Sari [H79G] mutant, which has the additional effect of causing COPII-associated membranes to cluster to a juxtanuclear region. In cells expressing Sar1[T39N], a constitutively inactive form of Sari that completely disrupts ER exit sites, Golgi glycosylation enzymes, matrix, and itinerant proteins all redistribute to the ER. These results argue against the hypothesis that the Golgi apparatus contains stable components that can serve as a template for its biogenesis. Instead, they suggest that the Golgi complex is a dynamic, steady-state system, whose membranes can be nucleated and are maintained by the activities of the Sar1-COPII and Arf1-coatomer systems. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Lib Dr, Bethesda, MD 20892 USA. RI Ward, Theresa/E-9650-2013 OI Ward, Theresa/0000-0002-9881-8649 NR 58 TC 306 Z9 311 U1 1 U2 17 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 12 PY 2001 VL 155 IS 4 BP 557 EP 570 DI 10.1083/jcb.200107045 PG 14 WC Cell Biology SC Cell Biology GA 494PQ UT WOS:000172291400008 PM 11706049 ER PT J AU Kovacs, A Wasserman, SS Burns, D Wright, DJ Cohn, J Landay, A Weber, K Cohen, M Levine, A Minkoff, H Miotti, P Palefsky, J Young, M Reichelderfer, P AF Kovacs, A Wasserman, SS Burns, D Wright, DJ Cohn, J Landay, A Weber, K Cohen, M Levine, A Minkoff, H Miotti, P Palefsky, J Young, M Reichelderfer, P CA DATRI WIHS Study Grp TI Determinants of HIV-1 shedding in the genital tract of women SO LANCET LA English DT Article; Proceedings Paper CT 6th Conference on Retroviruses and Opportunistic Infections CY JAN 31-FEB 04, 1999 CL CHICAGO, ILLINOIS ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 RNA LEVELS; MOTHER-TO-CHILD; HETEROSEXUAL TRANSMISSION; VIRAL LOAD; PERINATAL TRANSMISSION; CERVICOVAGINAL SECRETIONS; INFECTED WOMEN; RISK-FACTORS; BLOOD AB Background Plasma HIV-1 RNA concentration has been the best predictor for risk of heterosexual and perinatal transmission. However, direct contact with HIV-1 present locally in the genital tract might be necessary for transmission. We aimed to assess the relation between HIV-1 shedding (RNA or culturable virus) in female genital secretions and other factors that might affect HIV-1 shedding. Methods This was a cross-sectional study within the Women's Interagency HIV Study (WIHS), a prospective longitudinal cohort study of HIV-Infected women. We enrolled 311 HIV positive women from Jan 30, 1997 to July 1, 1998. We did clinical assessments, cultured HIV-1, and measured RNA in peripheral blood mononuclear cells (PBMC) and genital secretions. We compared the results with univariate and multivariate analyses. Presence of HIV-1 RNA or culturable virus in genital secretions was defined as HIV-1 shedding. Findings HIV-1 RNA was present in genital secretions of 57% (152/268) of women whereas infectious virus was detected only in 6% (17/271). Genital tract HIV-1 shedding was found in 80% (130/163) of women with detectable plasma RNA and 78% (116/148) of women with positive PBMC cultures. 33% (27/83) of women with less than 500 copies/mL plasma RNA and 39% (35/90) of those with negative PBMC cultures also had genital tract shedding. Interpretation Plasma RNA concentration, both qualitatively and quantitatively, was the most important factor in predicting genital HIV-1 shedding, even among women receiving potent antiretroviral therapy. However, HIV-1 shedding did occur in women with less than 500 copies/mL plasma HIV-1 RNA. This finding suggests that a separate reservoir of HIV-1 replication may exist in some women. C1 Univ So Calif, Sch Med, Comprehens Maternal Child & Adolescent HIV Manage, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Norris Canc Hosp, Los Angeles, CA 90033 USA. Univ Maryland, Dept Med, Baltimore, MD 21201 USA. NICHHD, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. Wayne State Univ, Sch Med, Div Infect Dis, Detroit, MI USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Maimonides Hosp, Brooklyn, NY 11219 USA. NIAID, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Kovacs, A (reprint author), Univ So Calif, Keck Sch Med, Los Angeles Cty Med Ctr, Comprehens Maternal Child & Adolescent HIV Manage, 1640 Marengo St,HRA Bldg, Los Angeles, CA 90033 USA. FU NIAID NIH HHS [U01-AI-42590, AI-34989, U01-AI-34993, U01-AI-35004, N01-AI-15123, U01-AI-31834, U01-AI-34994]; NICHD NIH HHS [U01-HD-32632] NR 40 TC 166 Z9 171 U1 0 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 10 PY 2001 VL 358 IS 9293 BP 1593 EP 1601 DI 10.1016/S0140-6736(01)06653-3 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 492VM UT WOS:000172188300013 PM 11716886 ER PT J AU Liang, W Hague, B Zhao, T Kindt, TJ AF Liang, W Hague, B Zhao, T Kindt, TJ TI HTLV-1 cell lines differ in constitutively activated signaling pathways that can be altered by cytokine exposure SO VIROLOGY LA English DT Article DE HTLV-1; Jak/STAT; cytokine; IL-4; IL-10 ID VIRUS TYPE-I; JAK-STAT PATHWAY; T-CELLS; JAK/STAT ACTIVATION; TAX PROTEIN; LEUKEMIA; EXPRESSION; TRANSCRIPTION; IL-10; PROLIFERATION AB Examination of signaling pathways used by HTLV-1-infected rabbit cell lines revealed differences between one, RH/K30, that mediates asymptomatic infection and another, RH/K34, that causes lethal experimental leukemia. Both lines are IL-2 independent; RH/K30 produces IL-4 while RH/K34 produces IL-10. Examination of the Jak/STAT (Janus kinase/signal transducer and activator of transcription) activation of the lines revealed constitutive phosphorylation of Jak1 in both. STAT6 phosphorylation, not previously reported for HTLV-1 cells, was observed in RH/K30; STAT1 and STAT3 were phosphorylated in RH/K34. Treatment with cytokines altered the activation of the STAT proteins: IL-2 induced STAT5 phosphorylation in both lines. Supernatant from RH/K34 or IL-10 induced STAT3 phosphorylation in RH/K30 cells. Supernatant from RH/K30 or IL-4 induced STAT6 phosphorylation in RH/K34 cells, which could be reversed with a Jak kinase inhibitor-AG-490. C1 NIAID, Mol & Cellular Immunogenet Sect, NIH, Bethesda, MD 20892 USA. RP Liang, W (reprint author), NIAID, Mol & Cellular Immunogenet Sect, NIH, Bldg 50,Room 5511,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2001 VL 290 IS 1 BP 91 EP 98 DI 10.1006/viro.2001.1156 PG 8 WC Virology SC Virology GA 497NY UT WOS:000172463400010 PM 11883009 ER PT J AU Minkoff, H Ahdieh, L Massad, LS Anastos, K Watts, DH Melnick, S Muderspach, L Burk, R Palefsky, J AF Minkoff, H Ahdieh, L Massad, LS Anastos, K Watts, DH Melnick, S Muderspach, L Burk, R Palefsky, J TI The effect of highly active antiretroviral therapy on cervical cytologic changes associated with oncogenic HPV among HIV-infected women SO AIDS LA English DT Article DE HAART; HIV; human papillomavirus; squamous intraepithelial lesions ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS INTRAEPITHELIAL LESIONS; PAPANICOLAOU SMEARS; RISK-FACTORS; NEOPLASIA; PREVALENCE; ABNORMALITIES; DYSPLASIA; AIDS AB Objective Cervical intraepithelial neoplasia (CIN), a common condition among HIV-infected women, has been linked to HIV load and immune status. Highly active antiretroviral therapy (HAART) improves immunologic and virologic status. This study was undertaken to determine the relationship between HAART use and CIN. Design Cohort study. The Women's Interagency HIV Study (WINS) in five cities in the USA (Bronx/Manhattan, New York; Brooklyn, New York; Chicago, Illinois; Los Angeles, California; San Francisco Bay area, California; Washington, District of Columbia). Methods HIV-infected women were followed every 6 months with Papanicolaou smears and cervicovaginal lavage for human papillomavirus (HPV) DNA testing. To characterize exposures that changed over time and to capture the dynamic nature of cytologic changes, Papanicolaou smear findings from each participant's consecutive visits were defined as a pair. We determined the proportion of all pairs that exhibited either regression or progression, according to HAART exposure, HPV results and Papanicolaou smear status. As participants could contribute multiple pairs, inferences were based on robust methods to adjust for correlated observations. Results Women with persistent HPV infection were more likely to have progression of their lesions. After adjustment for CD4 cell count and Papanicolaou smear status, women on HAART were 40% (95% confidence interval, 4-81%) more likely to demonstrate regression and less likely (odds ratio, 0.68; 95% confidence interval, 0.52-0.88) to demonstrate progression Conclusions HAART altered the course of HPV disease in HIV-infected women, reducing progression and increasing regression. As HPV disease is a common sex-specific manifestation of HIV disease this effect of HAART would be a major additional benefit from this modality of therapy. (C) 2001 Lippincott Williams & Wilkins. C1 Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. SUNY Hlth Sci Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. Johns Hopkins Univ, Sch Publ Hlth, Div Epidemiol, Baltimore, MD USA. Cook Cty Hosp, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Rush Med Coll, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. Lincoln Med & Mental Hlth Ctr, Dept Med, Bronx, NY USA. NICHHD, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Minkoff, H (reprint author), Maimonides Hosp, Dept Obstet & Gynecol, 967 48th St, Brooklyn, NY 11219 USA. FU NIAID NIH HHS [AI-34989, N01-AI-35161, U01-AI-31834, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-42590]; NICHD NIH HHS [U01-HD-35632] NR 56 TC 125 Z9 130 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 9 PY 2001 VL 15 IS 16 BP 2157 EP 2164 DI 10.1097/00002030-200111090-00011 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 495GU UT WOS:000172332500011 PM 11684935 ER PT J AU Mosser, VA Li, YH Quon, MJ AF Mosser, VA Li, YH Quon, MJ TI PTEN does not modulate GLUT4 translocation in rat adipose cells under physiological conditions SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE metabolism; signal transduction; insulin resistance; phosphatase; glucose ID TUMOR-SUPPRESSOR PTEN; INSULIN-STIMULATED TRANSLOCATION; PROTEIN-TYROSINE-PHOSPHATASE; FOCAL ADHESION KINASE; SIGNALING PATHWAY; COWDEN-DISEASE; PDZ DOMAIN; GENE; ACTIVATION; PTEN/MMAC1 AB PTEN is a 3'-inositol lipid phosphatase that dephosphorylates products of PI 3-kinase. Since PI 3-kinase is required for many metabolic actions of insulin, we investigated the role of PTEN in insulin-stimulated translocation of GLUT4. In control rat adipose cells, we observed a similar to2-fold increase in cell surface GLUT4 upon maximal insulin stimulation. Overexpression of wild-type PTEN abolished this response to insulin. Translocation of GLUT4 in cells overexpressing PTEN mutants without lipid phosphatase activity was similar to that observed in control cells. Overexpression of PTEN-CBR3 (mutant with disrupted membrane association domain) partially impaired translocation of GLUT4. In Cos-7 cells, overexpression of wild-type PTEN had no effect on ERK2 phosphorylation in response to acute insulin stimulation. However, Elk-1 phosphorylation in response to chronic insulin treatment was significantly decreased. Thus, when PTEN is overexpressed, both its lipid phosphatase activity and subcellular localization play a role in antagonizing metabolic actions of insulin that are dependent on PI 3-kinase but independent of MAP kinase. However, because translocation of GLUT4 in cells overexpressing a dominant inhibitory PTEN mutant (C124S) was similar to that of control cells, we conclude that endogenous PTEN may not modulate, metabolic functions of insulin under normal physiological conditions. (C) 2001 Academic Press. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 8C-218,10 Ctr Dr,MSC 1755, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 50 TC 13 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 9 PY 2001 VL 288 IS 4 BP 1011 EP 1017 DI 10.1006/bbrc.2001.5876 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 493VH UT WOS:000172243800043 PM 11689011 ER PT J AU Kiyatkin, EA Wise, RA AF Kiyatkin, EA Wise, RA TI Striatal hyperthermia associated with arousal: intracranial thermorecordings in behaving rats SO BRAIN RESEARCH LA English DT Article DE temperature; arousal; striatum; neural activation; heat production ID BRAIN TEMPERATURE; FEVER; STRESS; MECHANISMS; MODULATION; POTENTIALS; MICE AB Humans and experimental animals show strong increases in body temperature in response to a variety of stimuli presumed to have stress as their common denominator. To assess the brain's role in this 'emotional' hyperthermia. temperatures were continuously recorded in dorsal and ventral striatum and in deep temporal muscle of freely moving rats exposed to different arousing and mild stress stimuli (placement in the test cage. 20-s sound stimulation, i.v. saline injection. 3-min social interaction with conspecific, and 3-min tail-pinch). The stimuli caused brain hyperthermia of differing degrees but similar pattern, in both the dorsal and ventral striatum. Ventral striatum had similar to0.4 degreesC higher basal temperature than dorsal striatum, each of these brain temperatures was higher than that in deep temporal muscle, Maximal increases in brain temperature (similar to0.8-1.2 degreesC for 20-40 min) occurred upon placement in the test cages, during tail-pinch and during social interaction. all of which were accompanied by behavioral activation. These increases developed with short onset latencies (up to 5-15 s) and always preceded increases in muscle temperature. Significant but smaller increases in brain temperature (similar to0.2 degreesC for 4-6 min) were detected after sound stimulation and Lv. saline injection that induced minimal changes in behavior and no change in muscle temperature. Thus. it appears that brain hyperthermia can be triggered by quite different arousing or stressful stimuli that disturb an organism's homeostasis and demand adaptive responding. Although the exact mechanisms of local heat production in brain tissue remain to be confirmed, neuronal activation appears to be the primary triggering force behind changes in brain temperature that are sufficient to affect body temperature. Because most neural processes are temperature-dependent. change in local temperature may result in dramatic modulation of the efficiency of neural processes in situations critical for life-support and during adaptive behavior. Published by Elsevier Science B.V. C1 NIDA, Intramural Res Program, Behav Neurosci Branch, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Intramural Res Program, Behav Neurosci Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Wise, Roy/A-6465-2012 NR 36 TC 22 Z9 22 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 9 PY 2001 VL 918 IS 1-2 BP 141 EP 152 DI 10.1016/S0006-8993(01)02985-7 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 494TN UT WOS:000172302100017 PM 11684052 ER PT J AU Schindler, CW Zheng, JW Goldberg, SR AF Schindler, CW Zheng, JW Goldberg, SR TI Effects of cocaine and cocaine metabolites on cardiovascular function in squirrel monkeys SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; cocaine metabolites; blood pressure; heart rate; squirrel monkeys ID ANESTHETIZED RATS; CONSCIOUS RATS; IN-VITRO; COCAETHYLENE; HUMANS; TOXICITY; PHARMACOKINETICS; VASOCONSTRICTION; PHARMACOLOGY; NORCOCAINE AB The effects of cocaine and the cocaine metabolites norcocaine, ecgonine methyl ester, benzoylecgonine and cocaethylene were evaluated in conscious squirrel monkeys for their effects on blood pressure and heart rate. Norcocaine, ecgonine methyl ester and benzoylecgonine are produced in vivo following cocaine use. Cocaethylene is produced in vivo following concurrent cocaine and alcohol use. Increases in both blood pressure and heart rate were observed following cocaine doses of 0.3-3.0 mg/kg. Ecgonine methyl ester and benzoylecgonine had no effect on either parameter up to doses of 10.0 mg/kg. Norcocaine increased blood pressure, but was less potent than cocaine. Norcocaine did not affect heart rate at doses up to 3.0 mg/kg. In contrast to the other metabolites, cocaethylene increased blood pressure and heart rate similarly to cocaine, These results suggest that ecgonine methyl ester and benzoylecgonine are devoid of cardiovascular effects at doses comparable to cocaine and would not be expected to contribute to cocaine's overall cardiovascular effects. Norcocaine's effect on blood pressure might contribute to the cardiovascular effects of cocaine. but this metabolite is produced only at low levels in vivo. The one metabolite that might be expected to contribute to cocaine's overall cardiovascular effect is cocaethylene, although the degree of this contribution is not clear. Published by Elsevier Science B.V. C1 NIDA, Preclin Pharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Beijing Med Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China. RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 37 TC 5 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 9 PY 2001 VL 431 IS 1 BP 53 EP 59 DI 10.1016/S0014-2999(01)01406-6 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 496GT UT WOS:000172388400008 PM 11716843 ER PT J AU Sweet, DH Miller, DS Pritchard, JB AF Sweet, DH Miller, DS Pritchard, JB TI Ventricular choline transport - A role for organic cation transporter 2 expressed in choroid plexus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOLATERAL MEMBRANE-VESICLES; TISSUE DISTRIBUTION PATTERN; FUNCTIONAL-CHARACTERISTICS; RAT-KIDNEY; ANION TRANSPORTER; PROXIMAL TUBULES; APICAL MEMBRANE; BRAIN; CLONING; LOCALIZATION AB To determine whether organic cation transporter (OCT) family members might mediate choline transport in choroid plexus (CP), the handling of choline by cloned transporters and by intact CP isolated from the adult rat was investigated. Expression of OCT1 and OCT2 in Xenopus oocytes increased hemicholinium-3-sensitive choline uptake. In contrast, OCT3 did not mediate choline transport. Estimated K-m values for choline in rOCT1-, rOCT2-, and hOCT2-expressing oocytes were 346 +/- 50, 441 +/- 67, and 102 +/- 80 mum, respectively. Membrane potential was the major driving force for choline uptake in rat and human OCT2-expressing oocytes and in intact CP in vitro. Lowering of medium pH (6 versus 7.4) was equally effective at inhibiting choline uptake in CP, suggesting that there might be a non-OCT component of choline uptake that is responsive to an H+ gradient. However, choline efflux from CP was not stimulated by a trans-applied H+ gradient. Choline uptake by CP was Na+-independent with an estimated K-m of 183 mum. Reverse transcriptase-polymerase chain reaction detected OCT2 and OCT3, but not OCT1, mRNA expression in CP. Transfection of intact CP with a rOCT2/green fluorescent protein fusion construct resulted in strong apical membrane fluorescence with no detectable signal in the basal and lateral plasma membranes. These data indicate that OCT2 mediates choline transport across the ventricular membrane of CP. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Sweet, DH (reprint author), Univ Calif San Diego, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. RI Sweet, Douglas/H-7914-2013 OI Sweet, Douglas/0000-0002-8911-9184 NR 67 TC 98 Z9 100 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2001 VL 276 IS 45 BP 41611 EP 41619 DI 10.1074/jbc.M108472200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400012 PM 11553644 ER PT J AU Gallagher, PG Sabatino, DE Basseres, DS Nilson, DM Wong, C Cline, AP Garrett, LJ Bodine, DM AF Gallagher, PG Sabatino, DE Basseres, DS Nilson, DM Wong, C Cline, AP Garrett, LJ Bodine, DM TI Erythrocyte ankyrin promoter mutations associated with recessive hereditary spherocytosis cause significant abnormalities in ankyrin expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENHANCER-BLOCKING ACTIVITY; BETA-SPECTRIN GENE; TRANSGENIC MICE; GLOBIN GENE; DEFICIENCY; CELLS; DOMINANT; CTCF; METHYLATION; PROTEINS AB Ankyrin defects are the most common cause of hereditary spherocytosis (HS). In several kindreds with recessive, ankyrin-deficient HS, mutations have been identified in the ankyrin promoter that have been proposed to decrease ankyrin synthesis. We analyzed the effects of two mutations, - 108T to C and - 108T to C in cis with - 153G to A, on ankyrin expression. No difference between wild type and mutant promoters was demonstrated in transfection or gel shift assays in vitro. Transgenic mice with a wild type ankyrin promoter linked to a human (A)gamma -globin gene expressed gamma -globin in 100% of erythrocytes in a copy number-dependent, position-independent manner. Transgenic mice with the mutant -108 promoter demonstrated variegated gamma -globin expression, but showed copy number-dependent and position-independent expression similar to wild type. Severe effects in ankyrin expression were seen in mice with the linked -108/-153 mutations. Three transgenic lines had undetectable levels of (A)gamma -globin mRNA, indicating position-dependent expression, and four lines expressed significantly lower levels of (A)gamma -globin mRNA than wild type. Two of four expressing lines showed variegated gamma -globin expression, and there was no correlation between transgene copy number and RNA level, indicating copy number-independent expression. These data are the first demonstration of functional defects caused by HS-related, ankyrin gene promoter mutations. C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. NGHRI, Genet & Mol Biol Branch, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. Univ Estadual Campinas, Hemoctr, BR-13083970 Campinas, SP, Brazil. RP Gallagher, PG (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St,POB 208064, New Haven, CT 06520 USA. RI Basseres, Daniela/C-6623-2013 OI Basseres, Daniela/0000-0001-7745-3567 NR 40 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2001 VL 276 IS 45 BP 41683 EP 41689 DI 10.1074/jbc.M105844200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400021 PM 11527968 ER PT J AU Nishi, H Senoo, M Nishi, KH Murphy, B Rikiyama, T Matsumura, Y Habu, S Johnson, AC AF Nishi, H Senoo, M Nishi, KH Murphy, B Rikiyama, T Matsumura, Y Habu, S Johnson, AC TI p53 homologue p63 represses epidermal growth factor receptor expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR GENE; CELL-LINES; P53-RELATED PROTEIN; MUTATIONAL ANALYSIS; MOLECULAR-CLONING; BINDING FACTOR; RETINOIC ACID; HUMAN CANCERS; TRANSCRIPTION; PROMOTER AB Tumor suppressor p53 has been shown to transactivate epidermal growth factor receptor (EGFR) expression through binding to a putative p53 responsive element in the EGFR promoter between nucleotides -265 and -239 (EGFRp53RE). Isotypes of p63 gene products, recently identified as p53 relatives, have a similar function to transactivate several p53 target gene promoters. However, our results indicate that TAp63 gamma has a very low ability to bind to the EGFRp53RE and surprisingly represses both basal EGFR promoter activity and e dogenous EGFR expression. Transient transfection a says show that the EGFR promoter region between -348 and -293, containing two Sp1 sites, is crucial for the repression of the EGFR expression by TAp63 gamma. Mutations in these Spl sites in the reporter constructs result in loss of the TAp63 gamma repression effect. We further show that TAp63 gamma directly interacts with Sp1 by immunoprecipitation analysis and that TAp63 gamma impairs Spl binding to the target DNA site in electrophoretic mobility shift assays. These results suggest that TAp63 gamma is involved in the regulation of the EGFR gene expression through interactions with basal transcription factors. C1 NCI, Mol Biol Lab, CCR, NIH, Bethesda, MD 20892 USA. Tokai Univ, Sch Med, Dept Immunol, Isehara, Kanagawa 25911, Japan. RP Johnson, AC (reprint author), NCI, Mol Biol Lab, CCR, NIH, Bldg 37,Rm 2D18,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 63 TC 52 Z9 53 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2001 VL 276 IS 45 BP 41717 EP 41724 DI 10.1074/jbc.M101241200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400025 PM 11546792 ER PT J AU Abbott, DW Ivanova, VS Wang, XY Bonner, WM Ausio, J AF Abbott, DW Ivanova, VS Wang, XY Bonner, WM Ausio, J TI Characterization of the stability and folding of H2A.Z chromatin particles - Implications for transcriptional activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOSOME CORE PARTICLE; TETRAHYMENA-THERMOPHILA; HISTONE H2A.Z; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; STRUCTURAL-CHANGES; CRYSTAL-STRUCTURE; IONIC STRENGTHS; VARIANT; DNA AB H2A.Z and H2A.1 nucleosome core particles and oligonucleosome arrays were obtained using recombinant versions of these histones and a native histone H2B/H3/H4 complement reconstituted onto appropriate DNA templates. Analysis of the reconstituted nucleosome core particles using native polyacrylamide gel electrophoresis and DNase I footprinting showed that H2A.Z nucleosome core particles were almost structurally indistinguishable from its H2A.1 or native chicken erythrocyte counterparts. While this result is in good agreement with the recently published crystallographic structure of the H2A.Z nucleosome core particle (Suto, R. K., Clarkson, M J., Tremethick, D. J., and Luger, YL (2000) Nat. Struct. Biol. 7,1121-1124), the ionic strength dependence of the sedimentation coefficient of these particles exhibits a substantial destabilization, which is most likely the result of the histone H2A.Z-H213 dimer binding less tightly to the nucleosome. Analytical ultracentrifuge analysis of the H2A.Z 208-12, a DNA template consisting of 12 tandem repeats of a 208-base pair sequence derived from the sea urchin Lytechinus variegatus 5 S rRNA gene, reconstituted oligonucleosome complexes in the absence of histone HI shows that their NaCl-dependent folding ability is significantly reduced. These results support the notion that the histone H2A.Z variant may play a chromatin-destabilizing role, which may be important for transcriptional activation. C1 Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Univ Victoria, Dept Biochem & Microbiol, POB 3055,Petch Bldg,220, Victoria, BC V8W 3P6, Canada. EM jausio@uvic.ca NR 57 TC 100 Z9 104 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2001 VL 276 IS 45 BP 41945 EP 41949 DI 10.1074/jbc.M108217200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400054 PM 11551971 ER PT J AU Chew, LJ Yuan, XQ Scherer, SE Qie, L Huang, F Hayes, WP Gallo, V AF Chew, LJ Yuan, XQ Scherer, SE Qie, L Huang, F Hayes, WP Gallo, V TI Characterization of the rat GRIK5 kainate receptor subunit gene promoter and its intragenic regions involved in neural cell specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESTRICTIVE SILENCER FACTOR; SODIUM-CHANNEL GENE; GLUTAMATE-RECEPTOR; SYNAPTIC TRANSMISSION; REGULATORY ELEMENTS; MAMMALIAN-CELLS; AMPA RECEPTORS; GROWTH-FACTOR; ION CHANNELS; EXPRESSION AB The GRIK5 (glutamate receptor ionotropic kainate-5) gene encodes the kainate-preferring glutamate receptor subunit KA2. The GRIK5 promoter is TATA-less and GC-rich, with multiple consensus initiator sequences. Transgenic mouse lines carrying 4 kilobases of the GRIK5 5'-flanking sequence showed lacZ reporter expression predominantly in the nervous system. Reporter assays in central glial (CG-4) and non-neural cells indicated that a 1200-base pair (bp) 5'-flanking region could sustain neural cell-specific promoter activity. Transcriptional activity was associated with the formation of a transcription factor IID-containing complex on an initiator sequence located 1100 bp upstream of the first intron. In transfection studies, deletion of exonic sequences downstream of the promoter resulted in reporter gene activity that was no longer neural cell-specific. When placed downstream of the GRIK5 promoter, a 77-bp sequence from the deleted fragment completely silenced reporter expression in NIH3T3 fibroblasts while attenuating activity in CG-4 cells. Analysis of the 77-bp sequence revealed a functional SP1-binding site and a sequence resembling a neuron-restrictive silencer element. The latter sequence, however, did not display cell-specific binding of REST-like proteins. Our studies thus provide evidence for intragenic control of GRIK5 promoter activity and suggest that elements contributing to tissue-specific expression are contained within the first exon. C1 NICHHD, Sect Mol & Cellular Neurobiol, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. Catholic Univ Amer, Dept Biol, Washington, DC 20064 USA. RP Gallo, V (reprint author), NICHHD, Sect Mol & Cellular Neurobiol, Lab Cellular & Synapt Neurophysiol, NIH, Bldg 49,Rm 5A-78,49 Convent Dr, Bethesda, MD 20892 USA. NR 66 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2001 VL 276 IS 45 BP 42162 EP 42171 DI 10.1074/jbc.M101895200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400084 PM 11533047 ER PT J AU Lockwich, T Singh, BB Liu, XB Ambudkar, IS AF Lockwich, T Singh, BB Liu, XB Ambudkar, IS TI Stabilization of cortical actin induces internalization of transient receptor potential 3 (Trp3)-associated caveolar Ca2+ signaling complex and loss of Ca2+ influx without disruption of Trp3-inositol trisphosphate receptor association SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OPERATED HTRP3 CHANNELS; GLAND CELLS; PROTEIN-KINASE; F-ACTIN; STORE; ORGANIZATION; MEMBRANE; ENTRY; CYTOSKELETAL; DOMAINS AB Ca2+ influx via plasma membrane Trp3 channels is proposed to be regulated by a reversible interaction with inositol trisphosphate receptor (IP,R) in the endoplasmic reticulum. Condensation of the cortical actin layer has been suggested to physically disrupt this interaction and inhibit Trp3-mediated Ca2+ influx. This study examines the effect of cytoskeletal reorganization on the localization and function of Trp3 and key Ca2+ signaling proteins. Calyculin-A treatment resulted in formation of condensed actin layer at the plasma membrane; internalization of Trp3, G alpha (q/11), phospholipase C beta, and caveolin-1; and attenuation of 1-oleoyl-2-acetyl-sn-glycerol- and ATP-stimulated Sr2+ influx. Importantly, Trp3 and IP3R-3 remained co-localized inside the cell and were co-immunoprecipitated. Jasplakinolide also induced internalization of Trp3 and caveolin-1. Pretreatment of cells with cytochalasin D or staurosporine did not affect Trp3 but prevented calyculin-A-induced effects. Based on these data, we suggest that Trp3 is assembled in a caveolar Ca2+ signaling complex with IP3R, SERCA, G alpha (q/11), phospholipase C beta, caveolin-1, and ezrin. Furthermore, our data demonstrate that conditions which stabilize cortical actin induce loss of Trp3 activity due to internalization of the Trp3-signaling complex, not disruption of IP3R-Trp3 interaction. This suggests that localization of the Trp3-associated signaling complex, rather than Trp3-IP3R coupling, depends on the status of the actin cytoskeleton. C1 NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Rm 1N-113, Bethesda, MD 20892 USA. OI Singh, Brij/0000-0003-0535-5997 NR 42 TC 115 Z9 119 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2001 VL 276 IS 45 BP 42401 EP 42408 DI 10.1074/jbc.M106956200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400112 PM 11524429 ER PT J AU Yu, ST Cao, WQ Kashireddy, P Meyer, K Jia, YZ Hughes, DE Tan, YJ Feng, JC Yeldandi, AV Rao, MS Costa, RH Gonzalez, FJ Reddy, JK AF Yu, ST Cao, WQ Kashireddy, P Meyer, K Jia, YZ Hughes, DE Tan, YJ Feng, JC Yeldandi, AV Rao, MS Costa, RH Gonzalez, FJ Reddy, JK TI Human peroxisome proliferator-activated receptor alpha (PPAR alpha) supports the induction of peroxisome proliferation in PPAR alpha-deficient mouse liver SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACYL-COA OXIDASE; ACID BETA-OXIDATION; FUNCTIONAL-CHARACTERIZATION; TISSUE DISTRIBUTION; MICE LACKING; CDNA CLONING; GENE; EXPRESSION; RAT; IDENTIFICATION AB Peroxisome proliferators, which function as peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists, induce peroxisomal, microsomal, and mitochondrial fatty acid oxidation enzymes, in conjunction with peroxisome proliferation, in liver cells. Sustained activation of PPAR alpha leads to the development of liver tumors in rats and mice. The assertion that synthetic PPAR alpha ligands pose negligible carcinogenic risk to humans is attributable, in part, to the failure to observe peroxisome proliferation in human hepatocytes. To explore the mechanism(s) of species-specific differences in response to PPAR alpha ligands, we determined the functional competency of human PPAR alpha in vivo and compared its potency with that of mouse PPAR alpha. Recombinant adenovirus that expresses human or mouse PPAR alpha was produced and administered intravenously to PPAR alpha -deficient mice. Human as well as mouse PPAR alpha fully restored the development of peroxisome proliferator-induced immediate pleiotropic responses, including peroxisome proliferation and enhanced expression of genes involved in lipid metabolism as well as nonperoxisomal genes, such as CD36, Ly-6D, Rbp7, monoglyceride lipase, pyruvate dehydrogenase kinase-4, and CV, that have been identified recently to be up-regulated in livers with peroxisome proliferation. These studies establish that human PPAR alpha is functionally competent and is equally as dose-sensitive as mouse PPAR alpha in inducing peroxisome proliferation within the context of mouse liver environment and that it can heterodimerize with mouse retinoid X receptor, and this human PPAR alpha -mouse retinoid X receptor chimeric heterodimer transcriptionally activates mouse PPAR alpha target genes in a manner qualitatively similar to that of mouse PPAR alpha. C1 Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA. Univ Illinois, Coll Med, Dept Mol Genet, Chicago, IL 60607 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Reddy, JK (reprint author), Northwestern Univ, Sch Med, Dept Pathol, 303 E Chicago Ave, Chicago, IL 60611 USA. FU NCI NIH HHS [CA84472]; NIGMS NIH HHS [GM23750] NR 49 TC 51 Z9 51 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2001 VL 276 IS 45 BP 42485 EP 42491 DI 10.1074/jbc.M106480200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400121 PM 11551940 ER PT J AU Claing, A Chen, W Miller, WE Vitale, N Moss, J Premont, RT Lefkowitz, RJ AF Claing, A Chen, W Miller, WE Vitale, N Moss, J Premont, RT Lefkowitz, RJ TI beta-arrestin-mediated ADP-ribosylation factor 6 activation and beta(2)-adrenergic receptor endocytosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; PROTEIN-COUPLED RECEPTORS; PLASMA-MEMBRANE; CLATHRIN ADAPTER; GOLGI-COMPLEX; ARF6; GTPASE; CELLS; DOMAINS; BINDING AB beta -Arrestins are multifunctional adaptor proteins known to regulate internalization of agonist-stimulated G protein-coupled receptors by linking them to endocytic proteins such as clathrin and AP-2. Here we describe a previously unappreciated mechanism by which beta -arrestin orchestrates the process of receptor endocytosis through the activation of ADP-ribosylation factor 6 (ARF6), a small GTP-binding protein. Involvement of ARF6 in the endocytic process is demonstrated by the ability of GTP-binding defective and GTP hydrolysis-deficient mutants to inhibit internalization of the beta (2)-adrenergic receptor. The importance of regulation of ARF6 function is shown by the ability of the ARF GTPase-activating protein GIT1 to inhibit and of the ARF nucleotide exchange factor, ARNO, to enhance receptor endocytosis. Endogenous beta -arrestin is found in complex with ARNO. Upon agonist stimulation of the receptor, beta -arrestin also interacts with the GDP-liganded form of ARF6, thereby facilitating ARNO-promoted GTP loading and activation of the G protein. Thus, the agonist-driven formation of a complex including beta -arrestin, ARNO, and ARF6 provides a molecular mechanism that explains how the agonist-stimulated receptor recruits a small G protein necessary for the endocytic process and controls its activation. C1 Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. CNRS, Ctr Neurochim, UPR2356, F-67084 Strasbourg, France. NHLBI, Pulm Crit Care Med Branch, Nihon Univ, Bethesda, MD 20892 USA. RP Lefkowitz, RJ (reprint author), Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 FU NHLBI NIH HHS [HL16037] NR 44 TC 156 Z9 168 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2001 VL 276 IS 45 BP 42509 EP 42513 DI 10.1074/jbc.M108399200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400124 PM 11533043 ER PT J AU Carballo, E Cao, HP Lai, WS Kennington, EA Campbell, D Blackshear, PJ AF Carballo, E Cao, HP Lai, WS Kennington, EA Campbell, D Blackshear, PJ TI Decreased sensitivity of tristetraprolin-deficient cells to p38 inhibitors suggests the involvement of tristetraprolin in the p38 signaling pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TUMOR-NECROSIS-FACTOR; AU-RICH ELEMENTS; FINGER TRANSCRIPTION FACTOR; MESSENGER-RNA DEGRADATION; FACTOR-ALPHA; MAP KINASE; TNF-ALPHA; INFLAMMATORY DISEASE; PYRIDINYL IMIDAZOLES AB Treatment of macrophages with pyridinyl imidazole inhibitors of p38 protein kinases can inhibit lipopolysaccharide-stimulated tumor necrosis factor a secretion. However, bone marrow-derived macrophages from tristetraprolin (TTP)-deficient mice were less sensitive than normal macrophages to this effect of p38 inhibitors, despite evidence for normal p38 activation in response to lipopolysaccharide. TTP is known to cause decreased stability of tumor necrosis factor a and granulocyte-macrophage colony-stimulating factor mRNAs after binding to an AU-rich element in their 3'-untranslated regions. A recombinant TTP fusion protein could be phosphorylated by a recombinant p38 kinase in cell-free assays and was phosphorylated to the same extent by immunoprecipitated p38 derived from normal and TTP-deficient cells stimulated with lipopolysaccharide; in both cases, the enzyme activity was inhibited by the p38 inhibitors. TTP phosphorylation also was increased in intact macrophages after lipopolysaccharide stimulation, an effect that was blocked by the p38 inhibitors. Finally, TTP in mammalian cell extracts bound less well to an AU-rich element RNA probe than did the same amount of TTP following dephosphorylation. These results suggest that TTP may be a component of the signaling cascade, initiated by inflammatory stimuli and mediated in part by activation of p38, that ultimately leads to enhanced secretion of tumor necrosis factor a. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. AstraZeneca Pharmaceut, Macclesfield SK10 4TG, Cheshire, England. RP Blackshear, PJ (reprint author), NIEHS, Off Clin Res, POB 12233, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [Z01 ES090080-08] NR 43 TC 141 Z9 146 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 9 PY 2001 VL 276 IS 45 BP 42580 EP 42587 DI 10.1074/jbc.M104953200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400134 PM 11546803 ER PT J AU Vorel, SR Gardner, EL AF Vorel, SR Gardner, EL TI Drug addiction and the hippocampus - Response SO SCIENCE LA English DT Editorial Material ID RAT NUCLEUS-ACCUMBENS; VENTRAL SUBICULUM; DOPAMINE EFFLUX; STIMULATION; GLUTAMATE; RETRIEVAL; MEMORY C1 Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Vorel, SR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, 1300 Morris Pk Ave, Bronx, NY 10461 USA. NR 14 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 9 PY 2001 VL 294 IS 5545 BP U1 EP U1 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 491VF UT WOS:000172130200002 ER PT J AU Friesen, MD Rothman, N Strickland, PT AF Friesen, MD Rothman, N Strickland, PT TI Concentration of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in urine and alkali-hydrolyzed urine after consumption of charbroiled beef SO CANCER LETTERS LA English DT Article DE heterocyclic aromatic amine; broiled meat; carcinogen; PhIP; urine metabolites ID FOOD MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; HETEROCYCLIC AMINES; COLORECTAL-CANCER; CYTOCHROME P4501A2; COLON-CANCER; COOKED FOOD; WELL-DONE; RED MEAT; HUMANS; IDENTIFICATION AB Heterocyclic amines (HAs) and polycyclic aromatic hydrocarbons are carcinogenic products formed during the cooking of meat at moderate to high temperatures. We have previously shown that the urinary concentration of 1-hydroxypyrene-glucuronide, a metabolite of pyrene, increased significantly in ten subjects who had ingested charbroiled ground beef. We now report the time course and interindividual variation of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) concentration in the urine samples from these ten subjects. PhIP concentration was determined in both untreated and alkali-hydrolyzed urine to obtain estimates of the proportion of conjugated PhIP metabolites in each subject. PhIP was measured by gas chromatography-negative ion chemical ionization-mass spectrometry after derivatization with pentafluorobenzyl bromide. Ten healthy nonsmoking males consumed identical amounts of broiled beef on five consecutive days. The morning after the first day of broiled beef consumption, urinary concentration of PhIP increased 14-38 fold above mean pre-feed concentration of PhIP in individual alkali-hydrolyzed urine samples. Following cessation of broiled beef consumption, urinary PhIP concentration declined to near pre-feed levels within 48-72 hrs. The ratio of total alkali-labile PhIP metabolites to unmetabolized PhIP varied by about 2.7-fold among subjects, ranging from 18:1 to 48:1, suggesting that interindividual differences in PhIP metabolism occur and can be detected by this method. This study of urinary PhIP following ingestion of meat cooked by charbroiling, that contains both HAs and polycyclic aromatic hydrocarbons, extends previous studies of ingestion of pan-fried meat that contains primarily HAs. The results indicate that significant amounts of PhIP are bioavailable from ingestion of charbroiled ground beef and that measurement of proportions of alkali-labile PhIP metabolites and parent PhIP in human urine may yield information on individual metabolism of ingested PhIP. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Int Agcy Res Canc, Unit Gene Environm Interact, F-69372 Lyon, France. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. RP Strickland, PT (reprint author), 615 N Wolfe St, Baltimore, MD 21205 USA. RI Friesen, Marlin/D-7328-2012 FU NIEHS NIH HHS [P01-ES06052, P30-ES03819] NR 38 TC 23 Z9 24 U1 0 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 8 PY 2001 VL 173 IS 1 BP 43 EP 51 DI 10.1016/S0304-3835(01)00672-3 PG 9 WC Oncology SC Oncology GA 482ME UT WOS:000171579300007 PM 11578808 ER PT J AU Lin, HC Morin, PJ AF Lin, HC Morin, PJ TI A novel homozygous deletion at chromosomal band 6q27 in an ovarian cancer cell line delineates the position of a putative tumor suppressor gene SO CANCER LETTERS LA English DT Article DE homozygous deletion; 6q27; ovarian cancer ID HUMAN-MALIGNANT MELANOMA; LONG ARM; FREQUENT LOSS; HETEROZYGOSITY; CARCINOMAS; REGION; ALLELOTYPE; GRADE; TUMORIGENICITY; INVOLVEMENT AB Chromosomal band 6q27 is believed to contain a tumor suppressor gene important in the development of several cancer types, including ovarian cancer. However, repeated efforts to identify a tumor suppressor gene in this region have been unsuccessful. Because homozygous deletions have been useful in the positional cloning of a number of tumor suppressor genes, we initiated a systematic search for such deletions in ovarian cancer cell lines using 6q microsatellite markers. One of the cell lines, OV 167. was found to contain an 80 kb homozygous deletion encompassing marker D6S 193 at 6q27 but excluding nearby marker D6S297. No known genes were present in the deleted region. Because the homozygous deletion might affect the expression of nearby genes, we analyzed the expression of the two closest known genes flanking the deletion, RNASE6PL and RSK-3. The expression of these genes were unaffected by the homozygous deletion, suggesting that the functional target of the deletion is located between these two genes. A search of the region against expressed sequence tag (EST) databases revealed that it contained four sets of expressed sequences. The first expressed sequences were derived from a LINE repetitive element and were considered unlikely to represent a tumor suppressor gene. The other expressed sequence tags identified did not show homology to known genes and are currently being investigated. This data may significantly reduce the magnitude of the search for the 6q tumor suppressor gene as it suggests a small area as a prime target for investigation. Published by Elsevier Science Ireland Ltd. C1 NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Morin, PJ (reprint author), NIA, Cellular & Mol Biol Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 38 TC 5 Z9 7 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 8 PY 2001 VL 173 IS 1 BP 63 EP 70 DI 10.1016/S0304-3835(01)00677-2 PG 8 WC Oncology SC Oncology GA 482ME UT WOS:000171579300009 PM 11578810 ER PT J AU Shao, L Lewin, NE Lorenzo, PS Hu, ZJ Enyedy, IJ Garfield, SH Stone, JC Marner, FJ Blumberg, PM Wang, SM AF Shao, L Lewin, NE Lorenzo, PS Hu, ZJ Enyedy, IJ Garfield, SH Stone, JC Marner, FJ Blumberg, PM Wang, SM TI Iridals are a novel class of ligands for phorbol ester receptors with modest selectivity for the RasGRP receptor subfamily SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; TUMOR-CELL-LINES; ACTIVATOR-BINDING DOMAIN; CD-1 MOUSE SKIN; 12-MYRISTATE 13-ACETATE; INDOLACTAM-V; INHIBITORS; DISCOVERY; DELTA; CANCER AB Since 1990, the National Cancer Institute has performed extensive in vitro screening of compounds for anticancer activity. To date, more than 70 000 compounds have been screened for their antiproliferation activities against a panel of 60 human cancer cell lines. We probed this database to identify novel structural classes with a pattern of biological activity on these cell lines similar to that of the phorbol esters. The iridals form such a structural class. Using the program Autodock, we show that the iridals dock to the same position on the C1b domain of protein kinase C delta as do the phorbol esters, with the primary hydroxyl group of the iridal at the C3 position forming two hydrogen bonds with the amide group of Thr12 and with the carbonyl group of Leu 21 and the aldehyde oxygen of the iridal forming a hydrogen bond with the amide group of Gly23. Biological analysis of two iridals, NSC 631939 and NSC 631941, revealed that they bound to protein kinase C alpha with K-i values of 75.6 +/- 1.3 and 83.6 +/- 1.5 nM, respectively. Protein kinase C is now recognized to represent only one of five families of proteins with C1 domains capable of high-affinity binding of diacylglycerol and the phorbol esters. NSC 631939 and NSC 631941 bound to RasGRP3, a phorbol ester receptor that directly links diacylglycerol/phorbol ester signaling with Ras activation, with Ki values of 15.5 +/- 2.3 and 41.7 +/- 6.5 nM, respectively. Relative to phorbol 12,13-dibutyrate, they showed 15- and 6-fold selectivity for RasGRP3. Both compounds caused translocation of green fluorescent protein tagged RasGRP3 expressed in HEK293 cells, and both compounds induced phosphorylation of ERK1/2, a downstream indicator of Ras activation, in a RasGRP3-dependent fashion. We conclude that the iridals represent a promising structural motif for design of ligands for phorbol ester receptor family members. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Univ Michigan, Ctr Canc, Dept Internal Med, Drug Discovery Program, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Dept Med Chem, Drug Discovery Program, Ann Arbor, MI 48109 USA. Univ Cologne, Inst Biochem, D-50674 Cologne, Germany. Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada. RP Blumberg, PM (reprint author), NCI, Lab Cellular Carcinogenesis, Bldg 37,Room 3A01,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Wang, Shaomeng/E-9686-2010 NR 61 TC 28 Z9 28 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 8 PY 2001 VL 44 IS 23 BP 3872 EP 3880 DI 10.1021/jm010258f PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 490JK UT WOS:000172048600012 PM 11689073 ER PT J AU Xia, Y Yang, ZY Xia, P Hackl, T Hamel, E Mauger, A Wu, JH Lee, KH AF Xia, Y Yang, ZY Xia, P Hackl, T Hamel, E Mauger, A Wu, JH Lee, KH TI Antitumor agents. 211. Fluorinated 2-phenyl-4-quinolone derivatives as antimitotic antitumor agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BIOLOGICAL EVALUATION; TUBULIN; CYTOTOXICITY; COLCHICINE; IDENTIFICATION; INHIBITION AB Fluorinated 2-phenyl-4-quinolone derivatives were synthesized and evaluated in National Cancer Institute's 60 human tumor cell line in vitro screen. From the results, the ketone moiety plays an essential role in activity. Among the compounds tested, 2'-fluoro-6-pyrrol-2-phenyl-4-quinolone (13) exhibited the most potent cytotoxic activities (log GI(50) < -8.00) against renal and melanoma tumor cell lines. Compound 13 was also a potent inhibitor of tubulin polymerization (IC50 = 0.46 muM) and of radiolabeled colchicine binding to tubulin, with activities comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diagnosis,Frederick Canc Res, Frederick, MD 21702 USA. NCI, Screening Technol Branch,Frederick Canc Res & Dev, Dev Therapeut Program, Div Canc Treatment, Bethesda, MD 20892 USA. Hosp PLA 306, Dept Pharm, Beijing 100101, Peoples R China. RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. EM khlee@email.unc.edu FU NCI NIH HHS [CA-17625] NR 17 TC 107 Z9 108 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 8 PY 2001 VL 44 IS 23 BP 3932 EP 3936 DI 10.1021/jm0101085 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 490JK UT WOS:000172048600018 PM 11689079 ER PT J AU Zhang, Y Joseph, DB Bowen, WD Flippen-Anderson, JL Dersch, CM Rothman, RB Jacobson, AE Rice, KC AF Zhang, Y Joseph, DB Bowen, WD Flippen-Anderson, JL Dersch, CM Rothman, RB Jacobson, AE Rice, KC TI Synthesis and biological evaluation of tropane-like 1-{2-[bis(4-fluorophenyl)methoxy]ethyl}-4-(3-phenylpropyl) piperazine (GBR 12909) analogues SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DOPAMINE REUPTAKE INHIBITORS; BIOGENIC-AMINE TRANSPORTERS; HIGH-AFFINITY; MOUSE-BRAIN; GBR 12935; COCAINE ANALOG; BINDING-SITES; POTENT; SEROTONIN; ABUSE AB We have prepared azabicyclo [3.2.1] derivatives (C-3-substituted tropanes) that bind with high affinity to the dopamine transporter and inhibit dopamine reuptake. Within the series, 3-{2-[bis-(4-fluorophenyl)methoxyl ethylidene}-8-methyl-8-azabicyclo [3.2.1] octane (8) was found to have the highest affinity and selectivity for the dopamine transporter. These azabicyclo [3.2.1] (bridged piperidine) series of compounds differ from the well-known benztropines by a 2-carbon spacer between C-3 and a diarylmethoxy moiety. Interestingly, these new compounds demonstrated a much lower affinity for the muscarinic-1 site, at least a 100-fold decrease compared to benztropine. Replacing N-methyl with N-phenylpropyl in two of the compounds resulted in a 3-10-fold increase in binding affinity for the dopamine transporter. However, those compounds lost selectivity for the dopamine transporter over the serotonin transporter. Replacement of the ether oxygen in the diarylmethoxy moiety with a nitrogen atom gave relatively inactive amines, indicating the important role which is played by the ether oxygen in transporter binding. Reduction of the C-3 double bond in 8 gave 3 alpha -substituted tropanes, as shown by X-ray crystallographic analyses of 11, 12, and 19. The 3 alpha -substituted tropanes had lower affinity and less selectivity than the comparable unsaturated ligands. C1 NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, NIH, Bldg 8,Room B1-22, Bethesda, MD 20892 USA. EM kr2lf@nih.gov NR 41 TC 18 Z9 18 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 8 PY 2001 VL 44 IS 23 BP 3937 EP 3945 DI 10.1021/jm0101592 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 490JK UT WOS:000172048600019 PM 11689080 ER PT J AU Hummer, G Rasaiah, JC Noworyta, JP AF Hummer, G Rasaiah, JC Noworyta, JP TI Water conduction through the hydrophobic channel of a carbon nanotube SO NATURE LA English DT Article ID MOLECULAR-DYNAMICS; LIQUID WATER; SIMULATION; TRANSITION; PROTEINS; KINETICS; SYSTEMS; IONS AB Confinement of matter on the nanometre scale can induce phase transitions not seen in bulk systems(1). In the case of water, so-called drying transitions occur on this scale(2-5) as a result of strong hydrogen-bonding between water molecules, which can cause the liquid to recede from nonpolar surfaces to form a vapour layer separating the bulk phase from the surface(6). Here we report molecular dynamics simulations showing spontaneous and continuous filling of a nonpolar carbon nanotube with a one-dimensionally ordered chain of water molecules. Although the molecules forming the chain are in chemical and thermal equilibrium with the surrounding bath, we observe pulse-like transmission of water through the nanotube. These transmission bursts result from the tight hydrogen-bonding network inside the tube, which ensures that density fluctuations in the surrounding bath lead to concerted and rapid motion along the tube axis(7-9). We also rnd that a minute reduction in the attraction between the tube wall and water dramatically affects pore hydration, leading to sharp, two-state transitions between empty and filled states on a nanosecond timescale. These observations suggest that carbon nanotubes, with their rigid nonpolar structures(10,11), might be exploited as unique molecular channels for water and protons, with the channel occupancy and conductivity tunable by changes in the local channel polarity and solvent conditions. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Maine, Dept Chem, Orono, ME 04469 USA. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 28 TC 1892 Z9 1938 U1 63 U2 638 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 8 PY 2001 VL 414 IS 6860 BP 188 EP 190 DI 10.1038/35102535 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490AY UT WOS:000172029100042 PM 11700553 ER PT J AU Pannifer, AD Wong, TY Schwarzenbacher, R Renatus, M Petosa, C Bienkowska, J Lacy, DB Collier, RJ Park, S Leppla, SH Hanna, P Liddington, RC AF Pannifer, AD Wong, TY Schwarzenbacher, R Renatus, M Petosa, C Bienkowska, J Lacy, DB Collier, RJ Park, S Leppla, SH Hanna, P Liddington, RC TI Crystal structure of the anthrax lethal factor SO NATURE LA English DT Article ID PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; FACTOR CLEAVES; TOXIN; MACROPHAGES; PROTEIN; IDENTIFICATION; PROGRAM AB Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax(1-3). It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways(4-6). Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity. C1 Burnham Inst, La Jolla, CA 92037 USA. Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. RP Liddington, RC (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI Collier, R John/0000-0002-2427-4239 NR 31 TC 278 Z9 295 U1 2 U2 19 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 8 PY 2001 VL 414 IS 6860 BP 229 EP 233 DI 10.1038/n35101998 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490AY UT WOS:000172029100053 PM 11700563 ER PT J AU Guzick, DS Overstreet, JW Factor-Litvak, P Brazil, CK Nakajima, ST Coutifaris, C Carson, SA Cisneros, P Steinkampf, MP Hill, JA Xu, D Vogel, DL Natl Cooperative Reprod Med Network AF Guzick, DS Overstreet, JW Factor-Litvak, P Brazil, CK Nakajima, ST Coutifaris, C Carson, SA Cisneros, P Steinkampf, MP Hill, JA Xu, D Vogel, DL Natl Cooperative Reprod Med Network TI Sperm morphology, motility, and concentration in fertile and infertile men. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SEMEN ANALYSIS; QUALITY; COUNTS AB Background: Although semen analysis is routinely used to evaluate the male partner in infertile couples, sperm measurements that discriminate between fertile and infertile men are not well defined. Methods: We evaluated two semen specimens from each of the male partners in 765 infertile couples and 696 fertile couples at nine sites. The female partners in the infertile couples had normal results on fertility evaluation. The sperm concentration and motility were determined at the sites; semen smears were stained at the sites and shipped to a central laboratory for an assessment of morphologic features of sperm with the use of strict criteria. We used classification-and-regression-tree analysis to estimate threshold values for subfertility and fertility with respect to the sperm concentration, motility, and morphology. We also used an analysis of receiver-operating-characteristic curves to assess the relative value of these sperm measurements in discriminating between fertile and infertile men. Results: The subfertile ranges were a sperm concentration of less than 13.5 x 10(sup 6) per milliliter, less than 32 percent of sperm with motility, and less than 9 percent with normal morphologic features. The fertile ranges were a concentration of more than 48.0 x 10(sup 6) per milliliter, greater than 63 percent motility, and greater than 12 percent normal morphologic features. Values between these ranges indicated indeterminate fertility. There was extensive overlap between the fertile and the infertile men within both the subfertile and the fertile ranges for all three measurements. Although each of the sperm measurements helped to distinguish between fertile and infertile men, none was a powerful discriminator. The percentage of sperm with normal morphologic features had the greatest discriminatory power. Conclusions: Threshold values for sperm concentration, motility, and morphology can be used to classify men as subfertile, of indeterminate fertility, or fertile. None of the measures, however, are diagnostic of infertility. C1 Univ Rochester, Sch Med, Dept Obstet & Gynecol, Rochester, NY 14642 USA. Univ Calif Davis, Davis, CA 95616 USA. Columbia Univ, New York, NY USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Alabama, Birmingham, AL USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. RP Guzick, DS (reprint author), Univ Rochester, Sch Med, Dept Obstet & Gynecol, Box 668,601 Elmwood Ave, Rochester, NY 14642 USA. FU NICHD NIH HHS [U10 HD33172, U01 HD27006, U10 HD26975, U10 HD26981, U10 HD27001, U10 HD27009, U10 HD27049, U10 HD33173] NR 23 TC 535 Z9 572 U1 4 U2 35 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 8 PY 2001 VL 345 IS 19 BP 1388 EP 1393 DI 10.1056/NEJMoa003005 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 489VY UT WOS:000172014200004 PM 11794171 ER PT J AU Brodie, SG Xu, XL Qiao, WH Li, WM Cao, L Deng, CX AF Brodie, SG Xu, XL Qiao, WH Li, WM Cao, L Deng, CX TI Multiple genetic changes are associated with mammary tumorigenesis in Brca1 conditional knockout mice SO ONCOGENE LA English DT Article DE Brca1; p53; ErbB2; cyclin D1; c-Myc; tumorigenesis ID CANCER-SUSCEPTIBILITY GENES; DNA-DAMAGE RESPONSE; INTERACT IN-VIVO; BREAST-CANCER; CELL-CYCLE; TRANSGENIC MICE; TUMOR-FORMATION; MEIOTIC CELLS; 5 REGIONS; C-MYC AB Germline mutations in the tumor suppressor gene BRCA1 predispose women to breast cancer, however somatic mutations in the gene are rarely detected in sporadic cancers. To understand this phenomenon, we examined mouse models carrying conditional disruption of Brca1 in mammary epithelium in either p53 wild type (wt) or heterozygous backgrounds. Although a p53(+/-) mutation significantly accelerated tumorigenesis, both strains developed mammary tumors in a stochastic fashion, suggesting that multiple factors, in addition to p53 mutations, may be involved in Brca1 related tumorigenesis. A unique feature of Brca1 mammary tumors is their highly diverse histopathology accompanied by severe chromosome abnormalities. The tumors also display extensive genetic/molecular alterations, including overexpression of ErbB2, c-Myc, p27 and Cyclin D1 in the majority of tumors, while they were virtually ER alpha and p16 negative. Translocations involving p53 were also identified which lead to abnormal RNA and protein products. In addition, we generated cell lines from mammary tumors and found that the cells retained many of the genetic changes found in the primary tumors, suggesting that these genes may be players in Brca1-associated tumorigenesis. Despite their distinct morphology, all cultured tumor cells were Tamoxifen resistant but highly sensitive to Doxorubicin or irradiation, suggesting that these methods would be effective in treatment of this disease. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 63 TC 117 Z9 120 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 8 PY 2001 VL 20 IS 51 BP 7514 EP 7523 DI 10.1038/sj.onc.1204929 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 489DN UT WOS:000171976900008 PM 11709723 ER PT J AU Neill, JD Duck, LW Sellers, JC Musgrove, LC Kehrl, JH AF Neill, JD Duck, LW Sellers, JC Musgrove, LC Kehrl, JH TI A regulator of G Protein signaling, RGS3, inhibits gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion SO BMC CELL BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEINS; ANTERIOR-PITUITARY CELLS; PHOSPHOLIPASE-C; COUPLED RECEPTORS; ALPHA-SUBUNITS; DESENSITIZATION; GNRH; FAMILY; GAIP; BETA AB Background: Luteinizing hormone secreted by the anterior pituitary gland regulates gonadal function. Luteinizing hormone secretion is regulated both by alterations in gonadotrope responsiveness to hypothalamic gonadotropin releasing hormone and by alterations in gonadotropin releasing hormone secretion. The mechanisms that determine gonadotrope responsiveness are unknown but ay involve regulators of G protein signaling (RGSs). These proteins act by antagonizing or abbreviating interaction of G proteins with effectors such as phospholipase C beta. Previously, we reported that gonadotropin releasing hormone-stimulated second messenger inositol trisphosphate production was inhibited when RGS3 and gonadotropin releasing hormone receptor cDNAs were co-transfected into the COS cell line. Here, we present evidence for RGS3 inhibition of gonadotropin releasing hormone-induced luteinizing hormone secretion fro cultured rat pituitary cells. Results: A truncated version of RGS3 ( RGS3T = RGS3 314-519) inhibited gonadotropin releasing hormone-stimulated inositol trisphosphate production ore potently than did RSG3 in gonadotropin releasing hormone receptor-bearing COS cells. An RSG3/glutathione-S-transferase fusion protein bound ore S-35-Gq alpha than any other member of the G protein family tested. Adenoviral-mediated RGS3 gene transfer in pituitary gonadotropes inhibited gonadotropin releasing hormone-stimulated luteinizing hormone secretion in a dose-related fashion. Adeno-RGS3 also inhibited gonadotropin releasing hormone stimulated H-3-inositol phosphate accumulation, consistent with a molecular site of action at the Gq alpha protein. Conclusions: RGS3 inhibits gonadotropin releasing hormone-stimulated second messenger production (inositol trisphosphate) as well as luteinizing hormone secretion from rat pituitary gonadotropes apparently by binding and suppressing the transduction properties of Gq alpha protein function. A version of RGS3 that is amino-terminally truncated is even ore potent than intact RGS3 at inhibiting gonadotropin releasing hormone-stimulated inositol trisphosphate production. C1 Univ Alabama, Sch Med, Dept Physiol & Biophys, Birmingham, AL 35294 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Neill, JD (reprint author), Univ Alabama, Sch Med, Dept Physiol & Biophys, Birmingham, AL 35294 USA. FU NICHD NIH HHS [1-R01-HD 34862] NR 47 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD NOV 7 PY 2001 VL 2 AR 21 DI 10.1186/1471-2121-2-21 PG 10 WC Cell Biology SC Cell Biology GA 501NN UT WOS:000172691200001 PM 11716781 ER PT J AU Silverman, DHS Small, GW Chang, CY Lu, CS de Aburto, MAK Chen, W Czernin, J Rapoport, SI Pietrini, P Alexander, GE Schapiro, MB Jagust, WJ Hoffman, JM Welsh-Bohmer, KA Alavi, A Clark, CM Salmon, E de Leon, MJ Mielke, R Cummings, JL Kowell, AP Gambhir, SS Hoh, CK Phelps, ME AF Silverman, DHS Small, GW Chang, CY Lu, CS de Aburto, MAK Chen, W Czernin, J Rapoport, SI Pietrini, P Alexander, GE Schapiro, MB Jagust, WJ Hoffman, JM Welsh-Bohmer, KA Alavi, A Clark, CM Salmon, E de Leon, MJ Mielke, R Cummings, JL Kowell, AP Gambhir, SS Hoh, CK Phelps, ME TI Positron emission tomography in evaluation of dementia - Regional brain metabolism and long-term outcome SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ALZHEIMERS-DISEASE; DIFFERENTIAL-DIAGNOSIS; COGNITIVE DECLINE; FDG PET AB Context Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. Objective To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. Design, Setting, and Patients Positron emission tomography (PET) studies of [F-18]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. Main Outcome Measures Regional distribution of [F-18]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. Results Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neu ro pathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). Conclusion In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur. C1 Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Ahmanson Biol Imaging Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Kaiser Permanente, Dept Internal Med, Los Angeles, CA USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dept Clin Biochem, Pisa, Italy. Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. Duke Univ, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Dept Psychiat, Durham, NC 27710 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Univ Liege, Cyclotron Res Ctr, Liege, Belgium. NYU, Sch Med, Dept Psychiat, New York, NY USA. Max Planck Inst Neurol Res, Dept Neurol, D-50931 Cologne, Germany. Univ Calif San Diego, Div Nucl Med, San Diego, CA 92103 USA. RP Silverman, DHS (reprint author), Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Ahmanson Biol Imaging Ctr, CHS AR-144, Los Angeles, CA 90095 USA. FU NIA NIH HHS [P50 AG05128-07, AG10129, AG16570] NR 26 TC 464 Z9 487 U1 0 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 7 PY 2001 VL 286 IS 17 BP 2120 EP 2127 DI 10.1001/jama.286.17.2120 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 490CD UT WOS:000172032100031 PM 11694153 ER PT J AU Sostaric, JZ Riesz, P AF Sostaric, JZ Riesz, P TI Sonochemistry of surfactants in aqueous solutions: An EPR spin-trapping study SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ISOTOPE-EXCHANGE-REACTIONS; PULSE-RADIOLYSIS; HOT-SPOT; MULTIBUBBLE SONOLUMINESCENCE; THERMAL-DECOMPOSITION; ACOUSTIC CAVITATION; WATER MIXTURES; PHOTOFRIN-II; SONOLYSIS; ULTRASOUND AB The surfactant properties of solutes play an important role in the sonochemistry and sonoluminescence of aqueous solutions. Recently, it has been shown, for relatively low molecular weight surfactants, that these effects can be correlated with the Gibbs surface excess of the solute. In the present study we investigate whether this correlation is valid for relatively high molecular weight surfactants and the mechanisms of surfactant decomposition during sonolysis. Sonolysis of argon-saturated aqueous solutions of nonvolatile surfactants [n-alkanesulfonates, n-alkyl sulfates, n-alkylammoniopropanesulfonates (APS), and poly(oxyethylenes) (POE)] was investigated by EPR and spin-trapping with 3,5-dibromo-4-nitrosobenzenesulfonate. Secondary carbon radicals (-(CH)-C-.-), formed by abstraction reactions, were observed for all surfactants that were sonicated. The yield of primary carbon (-(CH2)-C-.) and methyl ((CH3)-C-.) radicals that are formed by pyrolysis is greatest for the zwitterionic (i.e., APS) and nonionic surfactants (i.e., POE). The yield of (-(CH)-C-.-) radicals was measured following sonolysis of n-alkyl anionic surfactants [sodium pentanesulfonate (SPSo), sodium octanesulfonate (SOSo), sodium octyl sulfate (SOS), and sodium dodecyl sulfate (SDS)]. In the concentration range of 0-0.3 mM, the -(CH)-C-.- radical yield increases in the order SDS approximate to SOS approximate to SOSo > SPSo. At higher concentrations, a plateau in the maximum (-(CH)-C-.-) radical yield is reached for each surfactant, which follows the order SPSo > SOS approximate to SOSo > SDS; i.e., the radical scavenging efficiency increases with decreasing n-alkyl chain length. A similar trend was observed for the (CH3)-C-. yield following sonolysis of a homologous series of n-alkyl APS surfactants. The results show that the Gibbs surface excess of certain nonvolatile surfactants does not correlate with the extent of decomposition following sonolysis in aqueous solutions. Instead, the decomposition of surfactants depends on their chemical structure and their ability to equilibrate between the bulk solution and the gas/solution interface of cavitation bubbles. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Sostaric, JZ (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RI Sostaric, Joe/A-6033-2008 NR 59 TC 55 Z9 55 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 7 PY 2001 VL 123 IS 44 BP 11010 EP 11019 DI 10.1021/ja010857b PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 490JR UT WOS:000172049200028 PM 11686706 ER PT J AU Lipsitz, RS Tjandra, N AF Lipsitz, RS Tjandra, N TI Carbonyl CSA restraints from solution NMR for protein structure refinement SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID LIQUID-CRYSTALLINE PHASE; HUMAN UBIQUITIN; AMINO-ACIDS; NITROGEN; PROTON; ANGLES C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Room 3513, Bethesda, MD 20892 USA. NR 17 TC 30 Z9 30 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 7 PY 2001 VL 123 IS 44 BP 11065 EP 11066 DI 10.1021/ja016854g PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 490JR UT WOS:000172049200035 PM 11686713 ER PT J AU Wiley, HE Gonzalez, EB Maki, W Wu, MT Hwang, ST AF Wiley, HE Gonzalez, EB Maki, W Wu, MT Hwang, ST TI Expression of CC chemokine receptor-7 and regional lymph node metastasis of B16 murine melanoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID I MALIGNANT-MELANOMA; CELL LOCALIZATION; CUTTING EDGE; TYROSINASE; INHIBITION; MIGRATION; FOLLICLES; RESPONSES; SURVIVAL; ADHESION C1 NIH, Ctr Canc Res, Dermatol Branch, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NIH, Ctr Canc Res, Dermatol Branch, Bldg 10,Rm 12N246,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. NR 32 TC 244 Z9 263 U1 2 U2 8 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 7 PY 2001 VL 93 IS 21 BP 1638 EP 1643 PG 6 WC Oncology SC Oncology GA 489ME UT WOS:000171994500012 PM 11698568 ER PT J AU Marrogi, AJ Khan, MA van Gijssel, HE Welsh, JA Rahim, H Demetris, AJ Kowdley, KV Hussain, SP Nair, J Bartsch, H Okby, N Poirier, MC Ishak, KG Harris, CC AF Marrogi, AJ Khan, MA van Gijssel, HE Welsh, JA Rahim, H Demetris, AJ Kowdley, KV Hussain, SP Nair, J Bartsch, H Okby, N Poirier, MC Ishak, KG Harris, CC TI Oxidative stress and p53 mutations in the carcinogenesis of iron overload-associated hepatocellular carcinoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NITRIC-OXIDE SYNTHASE; ENHANCED EXPRESSION; PRIMARY HEMOCHROMATOSIS; LIPID-PEROXIDATION; LUNG-CANCER; DNA-DAMAGE; IN-VIVO; LIVER; DISEASE; LOAD C1 NCI, Ctr Canc Res, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Pathol & Lab Med, Pittsburgh, PA USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. German Canc Res Ctr, D-6900 Heidelberg, Germany. Armed Forces Inst Pathol, Dept Hepat & Gastrointestinal Pathol, Washington, DC 20306 USA. RP Harris, CC (reprint author), NIH, Bldg 37,Rm 2C05,MSC 4255, Bethesda, MD 20892 USA. NR 35 TC 47 Z9 47 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 7 PY 2001 VL 93 IS 21 BP 1652 EP 1655 PG 4 WC Oncology SC Oncology GA 489ME UT WOS:000171994500014 PM 11698570 ER PT J AU Howe, HL Wingo, PA Thun, MJ Ries, LAG Rosenberg, HM Feigal, EG Edwards, BK AF Howe, HL Wingo, PA Thun, MJ Ries, LAG Rosenberg, HM Feigal, EG Edwards, BK TI Re: Annual report to the nation on the status of cancer (1973 through 1998), featuring cancer with recent increasing trends - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 N Amer Assoc Cent Canc Registries Inc, Springfield, IL USA. Ctr Dis Control & Prevent, CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA USA. Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Natl Ctr Hlth Stat, Div Vital Stat, Hyattsville, MD 20782 USA. RP Howe, HL (reprint author), N Amer Assoc Cent Canc Registries Inc, 2121 W White Oaks Dr, Springfield, IL USA. NR 1 TC 1 Z9 1 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 7 PY 2001 VL 93 IS 21 BP 1656 EP 1656 PG 1 WC Oncology SC Oncology GA 489ME UT WOS:000171994500016 ER PT J AU Ioannidis, JPA Rosenberg, PS Goedert, JJ Ashton, LJ Benfield, TL Buchbinder, SP Coutinho, RA Eugen-Olsen, J Gallart, T Katzenstein, TL Kostrikis, LG Kuipers, H Louie, LG Mallal, SA Margolick, JB Martinez, OP Meyer, L Michael, NL Operskalski, E Pantaleo, G Rizzardi, GP Schuitemaker, H Sheppard, HW Stewart, GJ Theodorou, ID Ullum, H Vicenzi, E Vlahov, D Wilkinson, D Workman, C Zagury, JF O'Brien, TR AF Ioannidis, JPA Rosenberg, PS Goedert, JJ Ashton, LJ Benfield, TL Buchbinder, SP Coutinho, RA Eugen-Olsen, J Gallart, T Katzenstein, TL Kostrikis, LG Kuipers, H Louie, LG Mallal, SA Margolick, JB Martinez, OP Meyer, L Michael, NL Operskalski, E Pantaleo, G Rizzardi, GP Schuitemaker, H Sheppard, HW Stewart, GJ Theodorou, ID Ullum, H Vicenzi, E Vlahov, D Wilkinson, D Workman, C Zagury, JF O'Brien, TR CA Int Meta Anal HIV Host Genetics TI Effects of CCR5-Delta 32, CCR2-641, and SDF-1 3 ' A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTOR GENE; ANTIRETROVIRAL THERAPY; INFECTED INDIVIDUALS; CORECEPTOR USAGE; AIDS PROGRESSION; CLINICAL COURSE; CELL COUNTS; VIRAL LOAD; CCR5 LOCUS AB Background: Studies relating certain chemokine and chemokine receptor gene alleles with the outcome of HIV-1 infection have yielded inconsistent results. Objective: To examine postulated associations of genetic alleles with HIV-1 disease progression. Design: Meta-analysis of individual-patient data. Setting: 19 prospective cohort studies and case-control studies from the United States, Europe, and Australia. Patients: Patients with HIV-1 infection who were of European or African descent. Measurements: Time to AIDS, death, and death after AIDS and HIV-1 RNA level at study entry or soon after seroconversion. Data were combined with fixed-effects and random-effects models. Results: Both the CCR5-Delta 32 and CCR2-641 alleles were associated with a decreased risk for progression to AIDS (relative hazard among seroconverters, 0.74 and 0.76, respectively; P = 0.01 for both), a decreased risk for death (relative hazard among seroconverters, 0.64 and 0.74; P < 0.05 for both), and lower HIV-1 RNA levels after seroconversion (difference, -0.18 log(10) copies/mL and -0.14 log(10) copies/mL; P < 0.05 for both). Having the CCR5-Delta 32 or CCR2-641 allele had no clear protective effect on the risk for death after development of AIDS. The results were consistent between seroconverters and seroprevalent patients. In contrast SDF-1 YA homozygotes showed no decreased risk for AIDS (relative hazard for seroconverters and seroprevalent patients, 0.99 and 1.03, respectively), death (relative hazard, 0.97 and 1.00), or death after development of AIDS (relative hazard, 0.81 and 0.97; P > 0.5 for all). Conclusions: The CCR5-Delta 32 and CCR2-641 alleles had a strong protective effect on progression of HIV-1 infection, but SDF-1 XA homozygosity carried no such protection. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP O'Brien, TR (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8016, Rockville, MD 20852 USA. RI Ioannidis, John/G-9836-2011; Kostrikis, Leondios/A-5330-2016; Pantaleo, Giuseppe/K-6163-2016 OI Kostrikis, Leondios/0000-0002-5340-7109; NR 47 TC 210 Z9 219 U1 1 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 6 PY 2001 VL 135 IS 9 BP 782 EP 795 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 489VT UT WOS:000172013700003 PM 11694103 ER PT J AU Sheifer, SE Manolio, TA Gersh, BJ AF Sheifer, SE Manolio, TA Gersh, BJ TI Unrecognized myocardial infarction SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID CORONARY-ARTERY DISEASE; EXERCISE TL-201 SCINTIGRAPHY; LEFT-VENTRICULAR DYSFUNCTION; BETA-ENDORPHIN LEVELS; ANGINA-PECTORIS; MENTAL STRESS; PAIN PERCEPTION; AUTONOMIC NEUROPATHY; DIABETES-MELLITUS; BLOOD-PRESSURE AB This review addresses myocardial infarctions that escape clinical recognition. It focuses on the prevalence, predisposing factors, and prognosis of these unrecognized infarctions, and incorporates data from relevant epidemiologic studies, basic science investigations, and review articles. These data indicate that at least one fourth of all myocardial infarctions are clinically unrecognized. The demographic characteristics and coronary risk factor profiles of persons with previously unrecognized myocardial infarctions appear to be similar to those of persons whose infarctions are clinically detected. Impaired symptom perception may contribute to lack of recognition, but both patients' and physicians' perceptions about the risk for myocardial infarction may also play an important role. Finally, mortality rates after unrecognized and recognized myocardial infarction are similar. Given the public health implications of unrecognized myocardial infarction, future studies should address screening strategies, risk stratification after detection of previously unrecognized myocardial infarction, and the role of standard postinfarction therapies in affected patients. C1 Georgetown Univ, Med Ctr, Div Cardiol, Fairfax, VA 22033 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Sheifer, SE (reprint author), Georgetown Univ, Med Ctr, Div Cardiol, 3700 Joseph Siewick Dr,Suite 102, Fairfax, VA 22033 USA. NR 88 TC 107 Z9 109 U1 0 U2 7 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 6 PY 2001 VL 135 IS 9 BP 801 EP 811 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 489VT UT WOS:000172013700005 PM 11694105 ER PT J AU Kar, SR Lebowitz, J Blume, S Taylor, KB Hall, LM AF Kar, SR Lebowitz, J Blume, S Taylor, KB Hall, LM TI SmtB-DNA and protein-protein interactions in the formation of the cyanobacterial metallothionein repression complex: Zn2+ does not dissociate the protein-DNA complex in vitro SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; BINDS; IONS; IDENTIFICATION; LOCUS AB The synechococcal metallothionein locus smt consists of two divergent genes: smtA coding for the metallothionein SmtA, and smtB coding for the trans-acting regulator SmtB. The latter binds at two inverted repeats, designated S1/S2 and S3/S4, in the overlapping promoter/operator sites between the two genes. We have determined the binding stoichiometries to the entire operator/promoter DNA and to the separate S1/S2 and S3/S4 half-operator oligonucletides using sedimentation equilibrium and sedimentation velocity measurements. The full promoter/operator DNA binds two SmtB dimers. The hydrodynamic behavior of this complex supports a compact nucleoprotein structure. Each separate S1/S2 and S3/S4 operator sequence also binds two dimers. An equal molar mixture of separate S1/S2 and S3/S4 operator sequences, in excess SmtB, forms a S1/S2-SmtB:SmtB-S3/S4 bridge complex. Combining these results with previously published binding interference data, which showed consecutive S1/S2 and S3/S4 SmtB occupancy on the operator/promoter DNA, we have developed a model for the establishment of the repression complex that appears to involve significant DNA compaction, presumably DNA bending, stabilized by SmtB-SmtB bridge interactions. DNase I footprinting titrations also showed consecutive S1/S2 and S3/S4 SmtB occupancy. The footprints expand considerably in the presence of Zn2+. Hence, SmtB remains bound to the operator sites when Zn2+ ions are present. This result is further supported by gel retardation assay. Failure of the metal ions to dissociate SmtB from the DNA points to a hitherto unknown function of SmtB in the regulation of the smt locus. C1 NIH, Div Bioengn & Phys Sci, ORS, Bethesda, MD 20892 USA. Univ Alabama, Grad Program Biophys Sci, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. RP Lebowitz, J (reprint author), NIH, Div Bioengn & Phys Sci, ORS, Bldg 13,Room 3N17,Off Bldg 13,Room 3E49,13 S Dr, Bethesda, MD 20892 USA. FU NCI NIH HHS [R29 CA075467] NR 27 TC 22 Z9 22 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 6 PY 2001 VL 40 IS 44 BP 13378 EP 13389 DI 10.1021/bi011289f PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 490NC UT WOS:000172057100029 PM 11683648 ER PT J AU Ribar, T Koenig, JL Bhargava, R AF Ribar, T Koenig, JL Bhargava, R TI FTIR imaging of polymer dissolution. 2. Solvent/nonsolvent mixtures SO MACROMOLECULES LA English DT Article ID POLY(METHYL METHACRYLATE); PENETRANT DIFFUSION; ATR SPECTROSCOPY; EVANESCENT FIELD; LIQUID-CRYSTALS; SYSTEMS; FILMS AB transform infrared (FTIR) spectroscopic imaging employing focal plane array (FPA) detection is used to study the dissolution of poly(alpha -methylstyrene) (PAMS) by solvent solutions containing systematically varied amounts of a nonsolvent. Sequential images were acquired as dissolution proceeded and the samples were not disturbed during image acquisition. Qualitative spatial and chemical distribution of each species within the field of view was obtained by analyzing images based on the characteristic vibrational modes of each species, while quantitative information was gathered through the calculation of individual concentration profiles along the chemical gradient. The images and absorbance profiles showed selective solvent penetration in all cases. In general, the dissolution rate of the polymer decreased linearly with the weight-percent of nonsolvent present in the solution. Anomalously high dissolution rates were observed for solutions containing similar to5-10% nonsolvent. This increase was attributed to the formation of a band of high polymer concentration perpendicular to solvent diffusion direction during the dissolution process. The efficacy of FTIR imaging in studying the spatiotemporal variation of microscopic gradient evolution in multicomponent systems is underscored. C1 Case Western Reserve Univ, Dept Macromol Sci, Cleveland, OH 44106 USA. NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. RP Koenig, JL (reprint author), Case Western Reserve Univ, Dept Macromol Sci, Cleveland, OH 44106 USA. OI Bhargava, Rohit/0000-0001-7360-994X NR 31 TC 28 Z9 29 U1 4 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD NOV 6 PY 2001 VL 34 IS 23 BP 8340 EP 8346 DI 10.1021/ma011152x PG 7 WC Polymer Science SC Polymer Science GA 489FN UT WOS:000171981500056 ER PT J AU Hinnebusch, AG AF Hinnebusch, AG TI Unleashing yeast genetics on a factor-independent mechanism of internal translation initiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID RIBOSOME ENTRY SITE; PROTEIN-SYNTHESIS; POLIOVIRUS RNA; VIRUS; EXPRESSION; COMPLEXES; CODONS; CELLS C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. NR 31 TC 1 Z9 1 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2001 VL 98 IS 23 BP 12866 EP 12868 DI 10.1073/pnas.241517998 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490WM UT WOS:000172076800005 PM 11698676 ER PT J AU Moskovitz, J Bar-Noy, S Williams, WM Berlett, BS Stadtman, ER AF Moskovitz, J Bar-Noy, S Williams, WM Berlett, BS Stadtman, ER TI Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OXIDATIVE STRESS; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; THIOREDOXIN REDUCTASE; ACTIVE-SITE; GENE; EXPRESSION; RESISTANCE; OVEREXPRESSION; RESTRICTION AB Oxidation of proteins by reactive oxygen species is associated with aging, oxidative stress, and many diseases. Although free and protein-bound methionine residues are particularly sensitive to oxidation to methionine sulfoxide derivatives, these oxidations are readily repaired by the action of methionine sulfoxide reductase (MsrA). To gain a better understanding of the biological roles of MsrA in metabolism, we have created a strain of mouse that lacks the MsrA gene. Compared with the wild type, this mutant: (i) exhibits enhanced sensitivity to oxidative stress (exposure to 100% oxygen); (ii) has a shorter lifespan under both normal and hyperoxic conditions; (iii) develops an atypical (tip-toe) walking pattern after 6 months of age; (iv) accumulates higher tissue levels of oxidized protein (carbonyl derivatives) under oxidative stress; and (v) is less able to up-regulate expression of thioredoxin reductase under oxidative stress. It thus seems that MsrA may play an important role in aging and neurological disorders. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Moskovitz, J (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. NR 27 TC 416 Z9 431 U1 5 U2 23 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2001 VL 98 IS 23 BP 12920 EP 12925 DI 10.1073/pnas.231472998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490WM UT WOS:000172076800019 PM 11606777 ER PT J AU Jones, JM Gellert, M AF Jones, JM Gellert, M TI Intermediates in V(D)J recombination: A stable RAG1/2 complex sequesters cleaved RSS ends SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-LIGASE-IV; DEPENDENT PROTEIN-KINASE; DOUBLE-STRAND BREAKS; CELL-CYCLE; RAG-2 ACCUMULATION; SIGNAL SEQUENCES; REPAIR FACTORS; XRCC4 PROTEIN; HISTONE H2AX; CODING ENDS AB Rearrangement of gene segments to generate antigen receptor coding regions depends on the RAG1/2 recombinase, which assembles a synaptic complex between two DNA signal sequences and then cleaves the DNA directly adjacent to the paired signals. After coupled cleavage of complementary signal sequences, virtually all of the cleaved signal ends remained associated with RAG1/2 instable complexes. These signal end complexes were distinct from various precleavage RAG1/2 signal complexes in that they were resistant to treatment with heparin. A mammalian joining apparatus consisting of purified Ku70/86, XRCC4, and DNA ligase IV proteins was sufficient to join deproteinized cleaved ends, but retention of signal sequences within the signal end complex blocked access to the DNA ends and prevented their joining by these proteins. Sequestration of cleaved ends within the signal end complex would account for the persistence of these ends in the cell after cleavage and may explain why they do not normally activate the DNA-damage-dependent cell cycle checkpoint. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gellert, M (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 241, Bethesda, MD 20892 USA. NR 49 TC 62 Z9 62 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2001 VL 98 IS 23 BP 12926 EP 12931 DI 10.1073/pnas.221471198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490WM UT WOS:000172076800020 PM 11606753 ER PT J AU Pierce, MM Maddelein, ML Roberts, BT Wickner, RB AF Pierce, MM Maddelein, ML Roberts, BT Wickner, RB TI A novel Rtg2p activity regulates nitrogen catabolism in yeast SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; SIGNALING PATHWAY; URE2P; PRION; PROTEIN; MITOCHONDRIA; TOR; LOCALIZATION AB The inactivity of Ure2p, caused by either a ure2 mutation or the presence of the [URE3] prion, increases DAL5 transcription and thus enables Saccharomyces cerevisiae to take up ureidosuccinate (USA+). Rtg2p regulates transcription of glutamate-repressible genes by facilitation of the nuclear entry of the Rtg1 and Rtg3 proteins. We find that rtg2 Delta cells take up USA even without the presence of [URE3]. Thus, the USA+ phenotype of rtg2 Delta strains is not the result generation of the [URE3] prion but is a regulatory effect. Because rtg1 Delta or rtg3 Delta mutations or the presence of glutamate do not produce the USA+ phenotype, this is a novel function of Rtg2p. The USA+ phenotype of rtg2 Delta strains depends on GLN3, is caused by overexpression of DAL5, and is blocked by mks1 Delta, but not by overexpression of Ure2p. These characteristics suggest that Rtg2p acts in the upstream part of the nitrogen catabolism regulation pathway. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov RI MADDELEIN, Marie-Lise/G-5395-2010 NR 43 TC 15 Z9 15 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2001 VL 98 IS 23 BP 13213 EP 13218 DI 10.1073/pnas.181486098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490WM UT WOS:000172076800069 PM 11687605 ER PT J AU Hikida, T Kaneko, S Isobe, T Kitabatake, Y Watanabe, D Pastan, I Nakanishi, S AF Hikida, T Kaneko, S Isobe, T Kitabatake, Y Watanabe, D Pastan, I Nakanishi, S TI Increased sensitivity to cocaine by cholinergic cell ablation in nucleus accumbens SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADDICTION; INTERNEURONS; INTEGRATION; SENSITIZATION; LOCALIZATION; SCOPOLAMINE; AMPHETAMINE; EXPRESSION; ACTIVATION; RECEPTORS AB Chronic exposure to cocaine causes long-lasting behavioral changes associated with cocaine reinforcement and addiction. An important neural substrate for cocaine addiction is the nucleus accurnbens (NAc), which receives dopaminergic input from the ventral tegmental area. Although the neural circuit of the NAc is controlled by several other neurotransmitters, their involvement in cocaine addiction remains elusive. In this investigation, we ablated cholinergic interneurons from the adult NAc with immunotoxin-mediated cell targeting and examined the role of acetylcholine transmitter in adaptive behavioral changes associated with cocaine reinforcement and addiction. Acute exposure to cocaine induced abnormal rotation in unilaterally cholinergic cell-eliminated mice, This abnormal turning was enhanced by repeated ex sure of cocaine. In bilaterally cholinergic cell-eliminated mice, chronic cocaine administration induced a prominent and progressive increase in locomotor activity. Moreover, these mice showed robust conditioned place preference with a lower dose of cocaine, compared with wild-type littermates. This investigation demonstrates that acetylcholine in the NAc plays a key role in both acute and chronic actions of cocaine. C1 Kyoto Univ, Grad Sch Biostudies, Fac Med, Dept Biol Sci, Kyoto 6068501, Japan. Kyoto Univ, Grad Sch Biostudies, Dept Mol & Syst Biol, Kyoto 6068501, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Nakanishi, S (reprint author), Kyoto Univ, Grad Sch Biostudies, Fac Med, Dept Biol Sci, Kyoto 6068501, Japan. NR 28 TC 63 Z9 66 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2001 VL 98 IS 23 BP 13351 EP 13354 DI 10.1073/pnas.231488998 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490WM UT WOS:000172076800093 PM 11606786 ER PT J AU Ulrich, T Dersch, CM Rothman, RB Jacobson, AE Rice, KC AF Ulrich, T Dersch, CM Rothman, RB Jacobson, AE Rice, KC TI Derivatives of 17-(2-methylallyl)-substituted noroxymorphone: Variation of the delta address and its effects on affinity and selectivity for the delta opioid receptor SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PLACE PREFERENCE; NALTRINDOLE; ANTAGONISTS; AGONISTS; BINDING; NALTREXONE; MORPHINE AB In an effort to establish the importance of the N-(2-methylallyl) substituent in the noroxymorphone series, several derivatives have been synthesized, retaining that N-substituent and modifying the delta address moiety. A few compounds showed moderate binding affinity and selectivity for the delta receptor; none displayed a pharmacological profile as exceptional as N-(2-methylallyl)noroxymorphindole, A second study showed that 3-O-methylation of all derivatives decreases binding affinity. The present results indicate that only a combination of the N-(2-methylallyl) group and an indole delta address provided high selectivity for the delta receptor. Published by Elsevier Science Ltd. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. EM kr21f@nih.gov NR 19 TC 1 Z9 2 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 5 PY 2001 VL 11 IS 21 BP 2883 EP 2885 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 484JF UT WOS:000171685900022 ER PT J AU Akari, H Bour, S Kao, S Adachi, A Strebel, K AF Akari, H Bour, S Kao, S Adachi, A Strebel, K TI The human immunodeficiency virus type 1 accessory protein Vpu induces apoptosis by suppressing the nuclear factor kappa B-dependent expression of antiapoptotic factors SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE TrCP; caspase; TNF-alpha; Bcl-xL; TRAF1 ID INDUCED CELL-DEATH; PLASMA-MEMBRANE; T-CELLS; PARTICLE RELEASE; CYTOCHROME-C; TRANSCRIPTION FACTORS; TRANSMEMBRANE DOMAIN; CYTOPLASMIC DOMAIN; CASPASE ACTIVATION; HIV-1 INFECTION AB Human immunodeficiency virus (HIV) type 1 Vpu is an integral membrane protein with a unique affinity for beta TrCP (TrCP), a key member of the SkpI-Cullin-F-box E3 ubiquitin ligase complex that is involved in the regulated degradation of cellular proteins, including I kappaB. Remarkably, Vpu is resistant to TrCP-mediated degradation and competitively inhibits TrCP-dependent degradation of I kappaB, resulting in the suppression of nuclear factor (NF)-kappaB activity in Vpu-expressing cells. We now report that Vpu, through its interaction with TrCP, potently contributes to the induction of apoptosis in HIV-infected T cells. Vpu-induced apoptosis is specific and independent of other viral proteins. Mutation of a TrCP-binding motif in Vpu abolishes its apoptogenic property, demonstrating a close correlation between this property of Vpu and its ability to inhibit NF-kappaB activity. The involvement of NF-kappaB in Vpu-induced apoptosis is further supported by the finding that the levels of antiapoptotic factors Bcl-xL, A1/Bfl-1, and TNF receptor-associated factor (TRAF)1, all of which are expressed in an NF-kappaB-dependent manner, are reduced and, at the same time, levels of active caspase-3 are elevated. Thus, Vpu induces apoptosis through activation of the caspase pathway by way of inhibiting the NF-kappaB-dependent expression of antiapoptotic genes. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Univ Tokushima, Sch Med, Dept Virol, Tokushima 7708503, Japan. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, NIH, 4-312 4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. NR 77 TC 94 Z9 100 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 5 PY 2001 VL 194 IS 9 BP 1299 EP 1311 DI 10.1084/jem.194.9.1299 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 492GF UT WOS:000172159500011 PM 11696595 ER PT J AU Baird, AE Warach, S Dambrosia, J AF Baird, AE Warach, S Dambrosia, J TI Prediction of outcome after stroke - Reply SO LANCET LA English DT Letter C1 NINCDS, NIH, Bethesda, MD 20892 USA. RP Baird, AE (reprint author), NINCDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 3 PY 2001 VL 358 IS 9292 BP 1553 EP 1554 DI 10.1016/S0140-6736(01)06608-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 490MN UT WOS:000172055800056 ER PT J AU Carroll-Pankhurst, C Engels, E Strickler, HD Goedert, JJ Wagner, J Mortimer, EA AF Carroll-Pankhurst, C Engels, E Strickler, HD Goedert, JJ Wagner, J Mortimer, EA TI Thirty-five year mortality following receipt of SV40-contaminated polio vaccine during the neonatal period SO BRITISH JOURNAL OF CANCER LA English DT Article DE SV40; poliovirus vaccines; cancer; newborns ID HUMAN BRAIN-TUMORS; PLEURAL MESOTHELIOMA; SIMIAN-VIRUS-40; CANCER; SV40; EXPOSURE; LYMPHOMA; RATES AB Early poliovirus vaccines, both inactivated and live attenuated, were inadvertently contaminated with simian virus 40 (SV40), a monkey virus known to be oncogenic for newborn hamsters. Although large epidemiologic studies have not identified an elevated cancer risk in persons who received SV40-contaminated vaccines, fragments of SV40 DNA have recently been identified in certain human tumours. We report the follow-up of a cohort of 1073 persons, unique because they received SV40-contaminated poliovirus vaccines as newborns in 1961-63. A previous report of the status of these subjects as of 1977-79 identified 15 deaths, none due to cancer. The present study utilized the National Death Index to identify deaths in the cohort for the years 1979-96. Expected deaths were calculated from Cleveland area sex-, age-, race- and year-specific mortality rates. Increased mortality from all causes was not found. 4 deaths from cancer were found compared to 3.16 expected (P = 0.77). However, 2 deaths from testicular cancer occurred, compared to 0.05 expected (P = 0.002), which may be a chance finding due to multiple comparisons. There were 2 deaths due to leukaemia, at non-significant finding, and no deaths due to tumours of the types putatively associated with SV40. Although these results are, for the most part, consistent with other negative epidemiologic investigations of risks from SV40-contaminated vaccines, further study of testicular cancer may be warranted, and it will be important to continue monitoring this cohort which is now reaching middle-age. (C) 2001 Cancer Research Campaign. C1 Case Western Reserve Univ, Mandel Sch Appl Social Sci, Cleveland, OH 44106 USA. NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. RP Carroll-Pankhurst, C (reprint author), Case Western Reserve Univ, Mandel Sch Appl Social Sci, Cleveland, OH 44106 USA. NR 21 TC 26 Z9 28 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 2 PY 2001 VL 85 IS 9 BP 1295 EP 1297 DI 10.1054/bjoc.2001.2065 PG 3 WC Oncology SC Oncology GA 495BA UT WOS:000172319300010 PM 11720463 ER PT J AU Engels, EA Rosenberg, PS Frisch, M Goedert, JJ AF Engels, EA Rosenberg, PS Frisch, M Goedert, JJ TI Cancers associated with Kaposi's sarcoma (KS) in AIDS: a link between KS herpesvirus and immunoblastic lymphoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE Kaposi's sarcoma; non-Hodgkin lymphoma; acquired immunodeficiency syndrome (AIDS); human immunodeficiency virus (HIV); Kaposi's sarcoma herpesvirus (KSHV) also known as human herpesvirus 8 ID MULTICENTRIC CASTLEMANS-DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS; CAVITY-BASED LYMPHOMAS; NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8 INFECTION; MULTIPLE-MYELOMA; KSHV/HHV-8; PATHWAY AB Kaposi's sarcoma (KS), common among persons with acquired immunodeficiency syndrome (AIDS), is caused by KS herpesvirus (KSHV) but whether KSHV causes other malignancies is uncertain. Using linked United States AIDS and cancer registries, we measured the incidence of specific malignancies in persons with AIDS (4-27 months after AIDS onset). We identified associations with KSHV by calculating a relative risk: cancer incidence in persons with KS (all were KSHV-infected) divided by incidence in persons without KS. Using Poisson regression, relative risks were adjusted for human immunodeficiency virus risk group, gender, age, race, and calendar year. We included 189 159 subjects (26 972 with KS). Immunoblastic lymphoma was significantly associated with KS (506 cases; relative risks: unadjusted 2.44, 95%Cl 2.00-2.96, adjusted 1.58, 95%Cl 1.29-1.93). Only one immunoblastic lymphoma had pleura as primary site. None of 37 other specified malignancies (other non-Hodgkin lymphomas, haematological malignancies, solid tumours) was significantly associated with KS. In summary, the association of immunoblastic lymphoma with KS was specific among examined malignancies and remained significant after statistical adjustment. Our findings, and the previously demonstrated presence of KSHV in the histologically related primary effusion lymphoma, suggest that KSHV is involved in the pathogenesis of some immunoblastic lymphomas. (C) 2001 Cancer Research Campaign. C1 NCI, Viral Epidemiol Branch, Rockville, MD USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Statens Serum Inst, Dept Epidemiol Res, Danish Epidemiol Sci Ctr, DK-2300 Copenhagen, Denmark. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, 6120 Execut Blvd, Rockville, MD USA. NR 37 TC 16 Z9 16 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 2 PY 2001 VL 85 IS 9 BP 1298 EP 1303 DI 10.1054/bjoc.2001.2052 PG 6 WC Oncology SC Oncology GA 495BA UT WOS:000172319300011 PM 11720464 ER PT J AU Landi, MT Baccarelli, A Calista, D Pesatori, A Fears, T Tucker, MA Landi, G AF Landi, MT Baccarelli, A Calista, D Pesatori, A Fears, T Tucker, MA Landi, G TI Combined risk factors for melanoma in a Mediterranean population SO BRITISH JOURNAL OF CANCER LA English DT Article DE melanoma; dysplastic nevi; Mediterranean populations; pigmentation; melanoma thickness; risk factors ID CUTANEOUS MALIGNANT-MELANOMA; SUN EXPOSURE; ITALIAN POPULATION; FAMILIAL MELANOMA; PIGMENTARY TRAITS; MELANOCYTIC NEVI; DYSPLASTIC NEVI; SUNSCREENS AB A case-control study of non-familial melanoma including 183 incident cases and 179 controls was conducted in North-Eastern Italy to identify important risk factors and determine how combination of these affects risk in a Mediterranean population. Presence of dysplastic nevi (OR = 4.2, 95% Cl = 2.4-7.4), low propensity to tan (OR = 2.4, 95% Cl = 1.1 -5.0), light eye (OR = 2.4, 95% Cl = 1.1-5.2), and light skin colour (OR = 4.1, 95% Cl = 1.4-12.1) were significantly associated with melanoma risk after adjustment for age, gender and pigmentation characteristics. A chart which identifies melanoma risk associated with combinations of these factors is presented; it can be used to identify subjects who would most benefit from preventive measures in Mediterranean populations. According to the combination of these factors, a relative risk range from 1 to 98.5 was found. Light skin colour, high number of sunburns with blistering, and low propensity to tan were significantly associated with melanoma thickness, possibly indicating that individuals with these characteristics underestimate their risk and seek attention when their lesion is already advanced. (C) 2001 Cancer Research Campaign. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Milan, EPOCA, Epidemiol Res Ctr, I-20122 Milan, Italy. Bufalini Hosp, Dermatol Unit, I-47023 Cesena, Italy. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Landi, G (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015; OI Baccarelli, Andrea/0000-0002-3436-0640; pesatori, angela/0000-0002-0261-3252 FU NCI NIH HHS [CA 65558-01A2, N02-CP-91026] NR 27 TC 50 Z9 50 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 2 PY 2001 VL 85 IS 9 BP 1304 EP 1310 DI 10.1054/bjoc.2001.2029 PG 7 WC Oncology SC Oncology GA 495BA UT WOS:000172319300012 PM 11720465 ER PT J AU Ye, W Chow, WH Lagergren, J Boffetta, P Boman, G Adami, WO Nyren, O AF Ye, W Chow, WH Lagergren, J Boffetta, P Boman, G Adami, WO Nyren, O TI Risk of adenocarcinomas of the oesophagus and gastric cardia in patients hospitalized for asthma SO BRITISH JOURNAL OF CANCER LA English DT Article DE asthma; gastro-oesophageal reflux; adenocarcinoma of the oesophagus and gastric cardia ID GASTROESOPHAGEAL-REFLUX DISEASE; BODY-MASS INDEX; PREVALENCE; CANCER; SWEDEN; SYMPTOMS; THERAPY; ALCOHOL; TOBACCO AB In the first cohort study of the question we followed 92 986 (42 663 men and 50 323 women) adult patients hospitalized for asthma in Sweden from 1965 to 1994 for an average of 8.5 years to evaluate their risk, of oesophageal and gastric cardia adenocarcinoma. Standardized incidence ratio (SIR) adjusted for gender, age and calendar year was used to estimate relative risk, using the Swedish nationwide cancer incidence rates as reference. Asthmatic patients overall had a moderately elevated risk for oesophageal adenocarcinoma (SIR = 1.5, 95% confidence interval Cl, 0.9-2.5) and gastric cardia cancer (SIR = 1.4, 95% Cl, 1.0-1.9). However, the excess risks were largely confined to asthmatic patients who also had a discharge record of gastro-oesophageal reflux (SIR = 7.5, 95% Cl, 1.6-22.0 and SIR = 7.1, 95% Cl, 3.1-14.0, respectively). No significant excess risk for oesophageal squamous-cell carcinoma or distal stomach cancer was observed. In conclusion, asthma is associated with a moderately elevated risk of developing oesophageal or gastric cardia adenocarcinoma. Special clinical vigilance vis-a-vis gastro-esophageal cancers seems unwarranted in asthmatic patients, but may be appropriate in those with clinically manifest gastro-oesophageal reflux. (C) 2001 Cancer Research Campaign. C1 Karolinska Inst, Dept Med Epidemiol, SE-17177 Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Uppsala Univ, Dept Med Sci Resp Med & Allergol, SE-75185 Uppsala, Sweden. Int Agcy Res Canc, Unit Environm Canc Epidemiol, F-69008 Lyon, France. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Ye, W (reprint author), Karolinska Inst, Dept Med Epidemiol, Box 281, SE-17177 Stockholm, Sweden. RI Ye, Weimin/A-5939-2008; OI Lagergren, Jesper/0000-0002-5143-5448 NR 31 TC 15 Z9 16 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 2 PY 2001 VL 85 IS 9 BP 1317 EP 1321 DI 10.1054/bjoc.2001.2094 PG 5 WC Oncology SC Oncology GA 495BA UT WOS:000172319300014 PM 11720467 ER PT J AU Lipardi, C Wei, Q Paterson, BM AF Lipardi, C Wei, Q Paterson, BM TI RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs SO CELL LA English DT Article ID DOUBLE-STRANDED-RNA; MESSENGER-RNA; C-ELEGANS; GENETIC INTERFERENCE; SYNTHASE GENE; NEUROSPORA; TRANSGENE; PLANTS; VIRUS; POLYMERASE AB In posttranscriptional gene silencing (PTGS), "quelling," and RNA interference (RNAi), 21-25 nucleotide RNA fragments are produced from the initiating dsRNA. These short interfering RNAs (siRNAs) mediate RNAi by an unknown mechanism. Here, we show that GFP and Pp-Luc siRNAs, isolated from a protein complex in Drosophila embryo extract, target mRNA degradation in vitro. Most importantly, these siRNAs, as well as a synthetic 21-nucleotide duplex GFP siRNA, serve as primers to transform the target mRNA into dsRNA. The nascent dsRNA is degraded to eliminate the incorporated target mRNA while generating new siRNAs in a cycle of dsRNA synthesis and degradation. Evidence is presented that mRNA-dependent siRNA incorporation to form dsRNA is carried out by an RNA-dependent RNA polymerase activity (RdRP). C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Paterson, BM (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 52 TC 276 Z9 379 U1 3 U2 21 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 2 PY 2001 VL 107 IS 3 BP 297 EP 307 DI 10.1016/S0092-8674(01)00537-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 489ZH UT WOS:000172022800002 PM 11701121 ER PT J AU Kaminski, RM Van Rijn, CM Turski, WA Czuczwar, SJ Van Luijtelaar, G AF Kaminski, RM Van Rijn, CM Turski, WA Czuczwar, SJ Van Luijtelaar, G TI AMPA and GABA(B) receptor antagonists and their interaction in rats with a genetic form of absence epilepsy SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE CGP 36742; LY 300164; AMPA/kainate receptor; GABA(B) receptor; absence epilepsy; WAG/Rij, rat; isobologram ID SPIKE-WAVE DISCHARGES; NON-NMDA; ANTICONVULSANT ACTIVITY; AMPA/KAINATE RECEPTORS; ANTIEPILEPTIC DRUGS; NONNMDA RECEPTORS; UNDERLYING SPIKE; KINDLING MODEL; ANIMAL-MODELS; INBRED STRAIN AB The effects of combined and single administration of the alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, 7,8-methylenedioxy-1-(4-aminophenyl)-4-methyl-3-acetyl-4,5-dihydro-2,3-benzodiazepine (LY 300164), and of the GABA(B) receptor antagonist gamma -aminopropyl-n-butyl-phosphinic acid (CGP 36742), on spontaneously occurring spike-wave discharges were investigated in WAG/Rij rats. LY 300164 had minor effects; only the highest dose (16 mg/kg) reduced the number of spike-wave discharges in a short time window. CGP 36742 was more effective as it significantly reduced the number of spike-wave discharges and shortened their duration at the doses of 25 and 100 mg/kg. The ED50 values for the inhibition of spike-wave discharges by LY 300164 and CGP 36742 in a time window 30-60 min after injection were 15.5 and 16.6 mg/kg, respectively. The ED50 of CGP 36742 was reduced to 8.0 mg/kg when this antagonist was administered in combination with LY 300164 (6 mg/kg). The interaction between the two antagonists appeared to be additive according to isobolographic analysis. Importantly, CGP 36742 and LY 300164 administered either alone or in combination had no apparent effects on behavior. These results may provide information for a rational approach to polytherapy for the treatment of generalized absence epilepsy. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Med Univ, Dept Pathophysiol, PL-20090 Lublin, Poland. Med Univ, Dept Pharmacol & Toxicol, PL-20090 Lublin, Poland. Inst Agr Med, Dept Toxicol, PL-20950 Lublin, Poland. Inst Agr Med, Isotope Lab, PL-20950 Lublin, Poland. Univ Nijmegen, Nijmegen Inst Cognit & Informat, Dept Comparat & Physiol Psychol, NL-6500 HE Nijmegen, Netherlands. RP Kaminski, RM (reprint author), NIDA, Addict Res Ctr, Integrat Neurosci Sect, Behav Neurosci Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI van Rijn, Clementina/D-5828-2012; van Luijtelaar, Gilles/D-2290-2010 NR 47 TC 30 Z9 30 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 2 PY 2001 VL 430 IS 2-3 BP 251 EP 259 DI 10.1016/S0014-2999(01)01393-0 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 495UT UT WOS:000172359300013 PM 11711038 ER PT J AU De Witt, BJ Marrone, JR Kaye, AD Keefer, LK Kadowitz, PJ AF De Witt, BJ Marrone, JR Kaye, AD Keefer, LK Kadowitz, PJ TI Comparison of responses to novel nitric oxide donors in the feline pulmonary vascular bed SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cat; circulation; diazeniumdiolate; diethylamine/NO; diethylenetriamine/NO; spermine/NO; sulfite/NO; Angeli's salt ID CONTROLLED BIOLOGICAL RELEASE; SMOOTH-MUSCLE RELAXATION; CYCLIC-GMP; COMPLEXES; MECHANISM; NO; HYPERTENSION; NUCLEOPHILES; NONOATES; AGENTS AB Pulmonary vascular responses to the novel diazeniumdiolate nitric oxide (NO) donors diethylamine/NO, diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt, were investigated and compared in the intact-chest cat. Under conditions of controlled blood flow, when tone in the pulmonary vascular bed had been raised to a high steady level, intralobar injections of diethylamine/NO (0.3-10 mug), diethylenetriamine/NO (10-30 mug), spermine/NO (10-30 mug), sulfite/NO (10-30 mug), and angeli's salt (10-30 mug) caused dose-related decreases in lobar arterial pressure without changing left atrial pressure. In terms of relative vasodilator activity in the pulmonary vascular bed, the dose of the compounds that decreased lobar arterial pressure 4 mm Hg (ED4 mm Hg) was significantly lower for diethylamine/NO compared to S-nitroso-N-acetylpenicillamine which was significantly less than diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt. The half-life of the vasodilator responses, as measured by 50% response recovery time, to diethylamine/NO, diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt was similar for doses with similar magnitudes of vasodilation, while the half-life to S-nitroso-N-acetylpenicillamine was significantly less than the diazeniumdiolate NO donors. The present data demonstrate that the diazeniumdiolate NO donors diethylamine/NO, diethylenetriamine/NO, spermine/NO, sulfite/NO, and angeli's salt have potent but relatively short-lasting vasodilator activity in the pulmonary vascular bed of the cat. (C) 2001 Published by Elsevier Science B.V. C1 Tulane Univ, Sch Med, Dept Pharmacol SL83, New Orleans, LA 70112 USA. Texas Tech Univ, Sch Med, Dept Anesthesiol, Lubbock, TX 79430 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Kadowitz, PJ (reprint author), Tulane Univ, Sch Med, Dept Pharmacol SL83, 1430 Tulane Ave, New Orleans, LA 70112 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NHLBI NIH HHS [HL-62000] NR 25 TC 19 Z9 19 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 2 PY 2001 VL 430 IS 2-3 BP 311 EP 315 DI 10.1016/S0014-2999(01)01289-4 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 495UT UT WOS:000172359300024 PM 11711049 ER PT J AU Jacobs, AR LeRoith, D Taylor, SI AF Jacobs, AR LeRoith, D Taylor, SI TI Insulin receptor substrate-1 pleckstrin homology and phosphotyrosine-binding domains are both involved in plasma membrane targeting SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; GLUT4 TRANSLOCATION; IN-VIVO; ACTIVATION; IRS-1; ADIPOCYTES; COMPARTMENTALIZATION; PHOSPHORYLATION; LOCALIZATION; ASSOCIATION AB The localization of insulin receptor substrate (IRS) molecules may be responsible for the differential biological activities of insulin and other peptides such as platelet-derived growth factor. The subcellular localization of IRS-1 is controversial, with some reports suggesting association with the cytoskeleton and other studies reporting membrane localization. In this study, we used immunofluorescence microscopy to define the localization of IRS-1. In the basal state, recombinant IRS-1 was localized predominantly in the cytoplasm. In response to insulin, recombinant IRS-1 translocated to the plasma membrane. We have also studied the localization of green fluorescent protein (GFP) fusion proteins. Unlike native IRS-1, a fusion protein containing GFP plus full-length IRS-1 appeared to localize in inclusion bodies. In contrast, when GFP was fused to the N terminus of IRS-1 (i.e. the pleckstrin homology and phosphotyrosine-binding domains), this fusion protein was targeted to the plasma membrane. Mutations of phosphoinositide-binding sites in both the pleckstrin homology and phosphotyrosine-binding domains significantly reduced the ability of Myc-tagged IRS-1 to translocate to the plasma membrane following insulin stimulation. However, these mutations did not cause a statistically significant impairment of tyrosine phosphorylation in response to insulin. This raises the possibility that IRS-1 tyrosine phosphorylation may occur prior to plasma membrane translocation. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. RP LeRoith, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Rm 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 32 TC 27 Z9 28 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 2 PY 2001 VL 276 IS 44 BP 40795 EP 40802 DI 10.1074/jbc.M105194200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488FM UT WOS:000171925600057 PM 11526109 ER PT J AU Li, YH Martin, LD Spizz, G Adler, KB AF Li, YH Martin, LD Spizz, G Adler, KB TI MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYRISTOYL-ELECTROSTATIC SWITCH; KINASE-C; SIGNAL-TRANSDUCTION; GOBLET CELLS; CGMP ANALOGS; IN-VITRO; ACTIVATION; RELEASE; ALPHA AB Hypersecretion of airway mucin characterizes numerous respiratory diseases. Although diverse pathological stimuli can provoke exocytotic release of mucin from secretory cells of the airway epithelium, mechanisms involved remain obscure. This report describes a new paradigm for the intracellular signaling mechanism regulating airway mucin secretion. Direct evidence is provided that the myristoylated alanine-rich C kinase substrate (MARCKS) is a central regulatory molecule linking secretagogue stimulation at the cell surface to mucin granule release by differentiated normal human bronchial epithelial cells in vitro. Down-regulation of MARCKS expression or disruption of MARCKS function in these cells inhibits the secretory response to subsequent stimulation. The intracellular mechanism controlling this secretory process involves cooperative action of two separate protein kinases, protein kinase C and cGMP-dependent protein kinase. Upon stimulation, activated protein kinase C phosphorylates MARCKS, causing translocation of MARCKS from the plasma membrane to the cytoplasm, where it is then dephosphorylated by a protein phosphatase 2A that is activated by cGMP-dependent protein kinase, and associates with both actin and myosin. Dephosphorylated cytoplasmic MARCKS would also be free to interact with mucin granule membranes and thus could link granules to the contractile cytoskeleton, mediating their movement to the cell periphery and subsequent exocytosis. These findings suggest several novel intracellular targets for pharmacological intervention in disorders involving aberrant secretion of respiratory mucin and may relate to other lesions involving exocytosis of membrane-bound granules in various cells and tissues. C1 N Carolina State Univ, Coll Vet Med, Dept Anat Physiol Sci & Radiol, Raleigh, NC 27606 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Adler, KB (reprint author), N Carolina State Univ, Coll Vet Med, Dept Anat Physiol Sci & Radiol, 4700 Hillsborough St, Raleigh, NC 27606 USA. FU NHLBI NIH HHS [R01 HL39862] NR 28 TC 103 Z9 110 U1 2 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 2 PY 2001 VL 276 IS 44 BP 40982 EP 40990 DI 10.1074/jbc.M105614200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488FM UT WOS:000171925600082 PM 11533058 ER PT J AU Hu, ZZ Meng, JP Dufau, ML AF Hu, ZZ Meng, JP Dufau, ML TI Isolation and characterization of two novel forms of the human prolactin receptor generated by alternative splicing of a newly identified exon 11 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; GENE; DEGRADATION; EXPRESSION; HORMONE; PROTEIN; LIVER; PATHWAYS; MULTIPLE; BINDING AB We have identified a novel exon 11 of the human prolactin receptor (hPRLR) gene that is distinct from its rodent counterparts and have demonstrated the presence of two novel short forms of the hPRLR (S1(a) and S1(b)), which are derived from alternative splicing of exons 10 and 11. S1(a) encodes 376 amino acids (aa) that contain partial exon 10 and a unique 39-aa C-terminal region encoded by exon 11. S1(b) encodes 288 as that lack the entire exon 10 and contains 3 amino acids at the C terminus derived from exon 11 using a shifted reading frame. These short forms, which were found in several normal tissues and in breast cancer cell lines, were expressed as cell surface receptors and possessed binding affinities comparable with the long form. Unlike the long form, neither short form was able to mediate the activation of the beta -casein gene promoter induced by prolactin. Instead they acted as dominant negative forms when co-expressed with the long form in transfected cells. Due to a marked difference in the cellular levels between the two short forms in transfected cells, S1(b) was more effective in inhibiting the prolactin-induced activation of the beta -casein gene promoter mediated by the long form of the receptor. The low cellular level of Sla was due to its more rapid turnover than the S1(b) protein. This is attributable to specific residues within the C-terminal unique 39 amino acids of the S1(a) form and may represent a new mechanism by which the hPRLR is modulated at the post-translational level. Since both short forms contain abbreviated cytoplasmic domains with unique C termini, they may also exhibit distinct signaling pathways in addition to modulating the signaling from the long form of the receptor. These receptors may therefore play important roles in the diversified actions of prolactin in human tissues. C1 NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, Bldg 49,Rm 6A36, Bethesda, MD 20892 USA. NR 34 TC 80 Z9 83 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 2 PY 2001 VL 276 IS 44 BP 41086 EP 41094 DI 10.1074/jbc.M102109200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488FM UT WOS:000171925600096 PM 11518703 ER PT J AU Cremo, CR Wang, F Facemyer, K Sellers, JR AF Cremo, CR Wang, F Facemyer, K Sellers, JR TI Phosphorylation-dependent regulation is absent in a nonmuscle heavy meromyosin construct with one complete head and one head lacking the motor domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; LIGHT-CHAIN; 2-HEADED STRUCTURE; IN-VITRO; 2 HEADS; ACTIN; SUBFRAGMENT-1; MECHANISM; BINDING AB To understand the domain requirements of phosphorylation-dependent regulation, we prepared three recombinant constructs of nonmuscle heavy meromyosin IIB containing 1) two complete heads, 2) one complete head and one head lacking the motor domain, and 3) one complete head and one head lacking both motor and regulatory domains. Steady-state ATPase measurements showed that phosphorylation did not alter the affinity for actin by more than a factor of 2 for any construct. Phosphorylation increased V-max by a factor of 10 for construct 1 and 1.5-3 for construct 2 but had no effect for construct 3. Single turnover measurements, a better measure of slow rates inherent to unphosphorylated regulated myosins, showed that the single-headed construct 2, like construct 3 retains less than 1% of the regulatory properties of the double-headed construct 1 (300-fold activation). Therefore, a complete head cannot be down-regulated by a regulatory domain (without the motor domain) on the partner head. Two motor domains are required for regulation. This result is predicted by a structural model (Wendt, T., Taylor, D., Messier, T., Trybus, K. M., and Taylor, K. A. (1999) J. Cell Biol. 147, 1385-1390) showing interaction between the motor domains for unphosphorylated smooth muscle myosin, if motor-motor interaction is the basis for down-regulation. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Univ Nevada, Dept Biochem, Reno, NV 89557 USA. RP Sellers, JR (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 34 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 2 PY 2001 VL 276 IS 44 BP 41465 EP 41472 DI 10.1074/jbc.M107103200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488FM UT WOS:000171925600143 PM 11517231 ER PT J AU Blanco, FJ Hess, S Pannell, LK Rizzo, NW Tycko, R AF Blanco, FJ Hess, S Pannell, LK Rizzo, NW Tycko, R TI Solid-state NMR data support a helix-loop-helix structural model for the N-terminal half of HIV-1 Rev in fibrillar form SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Rev protein; HIV; protein fibrils; solid-state NMR; structure determination ID HUMAN-IMMUNODEFICIENCY-VIRUS; C-13 CHEMICAL-SHIFT; RESPONSIVE ELEMENT RNA; PROTEIN EXPORT PATHWAY; TYPE-1 REV; ALPHA-HELIX; MAGIC-ANGLE; CRYSTAL-STRUCTURE; NUCLEAR EXPORT; BINDING-SITES AB Rev is a 116 residue basic protein encoded by the genome of human immunodeficiency virus type 1 (HIV-1) that binds to multiple sites in the Rev response element (RRE) of viral mRNA transcripts in nuclei of host cells, leading to transport of incompletely spliced and unspliced viral mRNA to the cytoplasm of host cells in the latter phases of the HIV-1 life cycle. Rev is absolutely required for viral replication. Because Rev aggregates and fibrillizes in solution at concentrations required for crystal growth or liquid state NMR measurements, high-resolution structural characterization of full-length Rev has not been possible. Previously, circular dichroism studies have shown that approximately 50% of the Rev sequence adopts helical secondary structure, predicted to correspond to a helix-loop-helix structural motif in the N-terminal half of the protein. We describe the application of solid-state NMR techniques to Rev fibrils as a means of obtaining site-specific, atomic-level structural constraints without requiring a high degree of solubility or crystallinity. Solid-state NMR measurements, using the double-quantum chemical shift anisotropy and constant-time double-quantum-filtered dipolar recoupling techniques, provide constraints on the phi and psi backbone dihedral angles at sites in which consecutive backbone carbonyl groups are labeled with C-13. Quantitative analysis of the solid-state NMR data, by comparison with numerical simulations, indicates helical phi and psi angles at residues Leu13 and Val16 in the predicted helix I segment, and at residues Arg39, Arg42, Arg43, and Arg44 in the predicted helix 2 segment. These data represent the first site-specific structural constraints from NMR spectroscopy on full-length Rev, and support the helix-loop-helix structural model for its N-terminal half. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Structural Mass Spectrometry Facil, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. RI Blanco, Francisco/D-4401-2009 OI Blanco, Francisco/0000-0003-2545-4319 NR 78 TC 38 Z9 39 U1 1 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 2 PY 2001 VL 313 IS 4 BP 845 EP 859 DI 10.1006/jmbi.2001.5067 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 490UB UT WOS:000172069600013 PM 11697908 ER PT J AU Tatum, J Sullivan, DC Kelloff, G AF Tatum, J Sullivan, DC Kelloff, G TI Congressional update: Report from the Biomedical Imaging Program of the National Cancer Institute - Molecular imaging and the microenvironment SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 NCI, Div Canc Treatment & Diag, Biomed Imaging Program, Rockville, MD 20852 USA. RP Sullivan, DC (reprint author), NCI, Div Canc Treatment & Diag, Biomed Imaging Program, Execut Plaza N,6130 Execut Blvd,Ste 600, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2001 VL 8 IS 11 BP 1192 EP 1193 DI 10.1016/S1076-6332(03)80736-5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 489JH UT WOS:000171987900013 PM 11721817 ER PT J AU Liberski, PP Guiroy, DC Williams, ES Walis, A Budka, H AF Liberski, PP Guiroy, DC Williams, ES Walis, A Budka, H TI Deposition patterns of disease-associated prion protein in captive mule deer brains with chronic wasting disease SO ACTA NEUROPATHOLOGICA LA English DT Article DE chronic wasting disease; immunocytochemistry; mule deer; prion diseases; transmissible spongiform encephalopathies ID ROCKY-MOUNTAIN ELK; CREUTZFELDT-JAKOB-DISEASE; CERVUS-ELAPHUS-NELSONI; WHITE-TAILED DEER; SPONGIFORM ENCEPHALOPATHY; ODOCOILEUS-HEMIONUS; AMYLOID PLAQUES; SCRAPIE; PRP; VARIANT AB Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) in captive and free-ranging cervids in the USA; its origin is obscure. Archival formalin-fixed and paraffin-embedded specimens of 16 captive mule deer brains with CWD were analyzed using immunocytochemistry for the disease-associated prion protein (PrP). The most prominent pattern of PrP deposition were plaque-like structures, a substantial proportion of which were florid plaques surrounded by a rim of spongiform vacuoles. The percentage of florid plaques was highly variable according to region, ranging from 0% to 52.7%. The highest percentage was observed in the medulla and basal ganglia, the lowest in the cerebral cortex. Only three brains contained no florid plaques. There were also punctate synaptic-type and perivascular deposits, particularly in areas of severe spongiform change, and subpial and subependymal plaque-like deposits, whereas cerebellar involvement was mild. Thus, CWD brain pathology prominently features florid PrP plaques, as does variant Creutzfeldt-Jakob disease (vCJD), but differs in other characteristics from vCJD. C1 Univ Vienna, Inst Neurol, A-1097 Vienna, Austria. Med Acad Lodz, Dept Mol Biol, Chair Oncol, Lodz, Poland. NINCDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. Univ Wyoming, Dept Vet Sci, Laramie, WY 82071 USA. RP Budka, H (reprint author), Univ Vienna, Inst Neurol, AKH 4J, A-1097 Vienna, Austria. OI Budka, Herbert/0000-0002-1933-1577 NR 35 TC 35 Z9 35 U1 0 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD NOV PY 2001 VL 102 IS 5 BP 496 EP 500 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 483XY UT WOS:000171662200013 PM 11699564 ER PT J AU Osuch, EA Cora-Locatelli, G Frye, MA Huggins, T Kimbrell, TA Ketter, TA Callahan, AM Post, RM AF Osuch, EA Cora-Locatelli, G Frye, MA Huggins, T Kimbrell, TA Ketter, TA Callahan, AM Post, RM TI Post-dexamethasone cortisol correlates with severity of depression before and during carbamazepine treatment in women but not men SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE dexamethasone; cortisol; depression; gender; menopause; carbamazepine ID CORTICOTROPIN-RELEASING HORMONE; SUPPRESSION TEST; DST; ILLNESS; AGE; PREDICTOR; GENDER AB Objective: Previous studies show a state-dependent relationship between depression and post-dexamethasone suppression test (DST) cortisol level, as well as differences in DST response with age and gender. Method: In this study, 74 research in-patients with affective disorders were given the DST on placebo and in a subgroup following treatment with carbamazepine. Depression was evaluated twice daily with the Bunney-Hamburg (BH) rating scale. Data were examined for the total subject population, by gender and by menopausal status in women. Results: A robust positive correlation was observed between depression severity and post-DST cortisol in pre- and postmenopausal females, but not in males. This relationship persisted in women when restudied on a stable dose of carbamazepine (n=42). Conclusion: The pathophysiological implications of this selective positive relationship between severity of depression and post-DST cortisol in women, but not men, should be explored further. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. N Little Rock VA Med Ctr, N Little Rock, AR USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Osuch, EA (reprint author), Uniformed Serv Univ Hlth Sci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. RI Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 NR 39 TC 12 Z9 12 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD NOV PY 2001 VL 104 IS 5 BP 397 EP 401 DI 10.1034/j.1600-0447.2001.00395.x PG 5 WC Psychiatry SC Psychiatry GA 485VY UT WOS:000171785200013 PM 11722323 ER PT J AU Cohen, SG Rizzo, PL AF Cohen, SG Rizzo, PL TI Asthma among the famous - Last of series - Patrick O'Brian (1914-2000) - British author SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Biographical-Item C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD NOV-DEC PY 2001 VL 22 IS 6 BP 383 EP 392 PG 10 WC Allergy SC Allergy GA 502ZP UT WOS:000172772900010 PM 11775397 ER PT J AU Sheps, DS Kaufmann, PG Sheffield, D Light, KC McMahon, RP Bonsall, R Maixner, W Carney, RM Freedland, KE Cohen, JD Goldberg, AD Ketterer, MW Raczynski, JM Pepine, CJ AF Sheps, DS Kaufmann, PG Sheffield, D Light, KC McMahon, RP Bonsall, R Maixner, W Carney, RM Freedland, KE Cohen, JD Goldberg, AD Ketterer, MW Raczynski, JM Pepine, CJ TI Sex differences in chest pain in patients with documented coronary artery disease and exercise-induced ischemia: Results from the PIMI study SO AMERICAN HEART JOURNAL LA English DT Article ID ENDORPHIN PLASMA-LEVELS; BETA-ENDORPHIN; MYOCARDIAL-ISCHEMIA; MENSTRUAL-CYCLE; GENDER; ANALGESIA; SENSITIVITY; PERCEPTION; STRESS; INFARCTION AB Background Sex differences in the pathophysiologic course of coronary artery disease (CAD) are widely recognized, yet accurate diagnosis of coronary artery disease in women remains challenging. Methods To determine sex differences in the clinical manifestation of CAD, we studied chest pain reported during daily activities, exercise, and mental stress in 170 men and 26 women. All patients had documented CAD (> 50% narrowing in at least 1 major coronary artery or prior myocardial infarction) and all had 1-mm ST-segment depression on treadmill exercise. We collected psychologic test results, serum samples (potassium, epinephrine, norepinephrine, cortisol, beta -endorphin, and glucose), and cardiac function, sensory threshold, and autonomic function data at specified times before, during, or after exercise and mental stress tests to assess measures of depression, anxiety, and neurohormonal and thermal pain perception. Results Women reported chest pain more often than men during daily activities (P = .04) and during laboratory mental stressors (P = .01) but not during exercise. Men had lower scores than women on measures of depression, trait anxiety, harm avoidance, and reward dependence (P < .05 for all). Women had significantly lower plasma (beta -endorphin levels at rest (4.2 +/- 3.9 vs 5.0 +/- 2.5 pmol/L for men; P = .005) and at maximal mental stress (6.4 +/- 5.1 vs 7.4 +/- 3.5 pmol/L for men, P < .01). A higher proportion of women than men had marked pain sensitivity to graded heat stimuli applied to skin (hot pain threshold < 41 degreesC, 33% vs 10%, P = .001). Conclusions Our results reflect sex differences in the affective and discriminative aspects of pain perception and may help explain sex-related differences in clinical presentations. C1 Univ Florida, Coll Med, Gainesville, FL 32610 USA. Malcom Randall Vet Affairs Med Ctr, Gainesville, FL USA. Dept Vet Affairs, Med Res Serv, Gainesville, FL USA. NHLBI, Bethesda, MD 20892 USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Univ N Carolina, Chapel Hill, NC USA. Emory Univ, Sch Med, Atlanta, GA USA. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. Washington Univ, Sch Med, St Louis, MO USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Alabama, Birmingham, AL USA. RP Sheps, DS (reprint author), Univ Florida, Coll Med, POB 100277, Gainesville, FL 32610 USA. RI McMahon, Robert/C-5462-2009; OI Sheffield, David/0000-0001-9121-1783 FU NHLBI NIH HHS [HV18114, HV18119, HV18120, HV18121, HV28127] NR 36 TC 37 Z9 39 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2001 VL 142 IS 5 BP 864 EP 871 DI 10.1067/mhj.2001.119133 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 491JE UT WOS:000172104600020 PM 11685176 ER PT J AU Yee, AJ Fuerst, T Salamone, L Visser, M Dockrell, M Van Loan, M Kern, M AF Yee, AJ Fuerst, T Salamone, L Visser, M Dockrell, M Van Loan, M Kern, M TI Calibration and validation of an air-displacement plethysmography method for estimating percentage body fat in an elderly population: a comparison among compartmental models SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE body composition; elderly; men; women; hydrostatic weighing; air-displacement plethysmography; multicompartment models; body density; percentage body fat ID 4-COMPARTMENT MODEL; WOMEN; AGE; DENSITY; WATER; MASS; MEN AB Background: The use of hydrostatic weighing (HW) to measure body composition in the elderly can be difficult and is based on the assumption of constancy of body compartments. Objective: We calibrated and validated a new air-displacement plethysmography (AP) method for measuring body composition in the elderly. Design: A 4-compartment equation for calculating percentage body fat (%BF) that used body density (D-b), total body water, and bone mineral content was used as the criterion for evaluating %BF estimated by the 2- and 3-compartment models. Db was measured by HW [D-b(HW)] and by use of the AP instrument [D-b(AP)] in 30 elderly men and 28 elderly women aged 70-79 y. Results: D-b(AP) was not significantly different from D-b(HW). However, analysis of variance showed a significant two-way interaction between sex and compartment model (P < 0.02), indicating that the comparisons between the sexes were different across all compartment models. The %BF calculated for the women was significantly higher than that calculated for the men by both HW and AP and for all compartment models. Conclusion: Our data indicate that D-b(AP) was not significantly different from D-b(HW). Although differences were seen in %BF between the sexes, we observed no significant differences among the compartment models within each sex for this group of older individuals. C1 San Francisco State Univ, Dept Kinesiol, Exercise Physiol Lab, San Francisco, CA 94132 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Calif Davis, USDA, Western Human Nutr Res Ctr, Davis, CA 95616 USA. RP Kern, M (reprint author), San Francisco State Univ, Dept Kinesiol, Exercise Physiol Lab, 1600 Holloway Ave, San Francisco, CA 94132 USA. FU NCRR NIH HHS [RR11805-02]; NIA NIH HHS [AG62106] NR 27 TC 16 Z9 18 U1 1 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2001 VL 74 IS 5 BP 637 EP 642 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 485TG UT WOS:000171779500015 PM 11684532 ER PT J AU Rapuri, PB Gallagher, JC Kinyamu, HK Ryschon, KL AF Rapuri, PB Gallagher, JC Kinyamu, HK Ryschon, KL TI Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE caffeine; bone loss; vitamin D receptor genotype; bone mineral density; elderly women ID POSTMENOPAUSAL WOMEN; MINERAL-DENSITY; GENE POLYMORPHISMS; CALCIUM-ABSORPTION; HIP FRACTURE; RISK-FACTORS; PREMENOPAUSAL WOMEN; OSTEOPOROTIC WOMEN; DIETARY CALCIUM; MASS AB Background: The role of caffeine as a risk factor for bone loss is controversial. Objective: Our goals were 1) to compare in both a cross-sectional study and a 3-y longitudinal study the bone mineral density (BMD) of postmenopausal women consuming high or low amounts of caffeine and 2) to study the interaction between caffeine intake, vitamin D receptor (VDR) polymorphism, and BMD in the longitudinal study. Design: The results are derived from cross-sectional measurements of BMD in 489 elderly women (aged 65-77 y) and from longitudinal measurements made in 96 of these women who were treated with a placebo for 3 y. Changes in BMD were adjusted for confounding factors and were compared between group, with either low (less than or equal to 300 mg/d) or high (> 300 mg/d) caffeine intakes and between the VDR genotype subgroups of the low- and high-caffeine groups. Results: Women with high caffeine intakes had significantly higher rates of bone loss at the spine than did those with low intakes (-1.90 +/- 0.97% compared with 1.19 +/- 1.08%; P = 0.038). When the data were analyzed according to VDR genotype and caffeine intake, women with the tt genotype had significantly (P = 0.054) higher rates of bone loss at the spine (-8.14 +/- 2.62%) than did women with the TT genotype (-0.34 +/- 1.42%) when their caffeine intake was >300 mg/d. Conclusions: Intakes of caffeine in amounts >300 mg/d (approximate to 514 g, or 18 oz, brewed coffee) accelerate bone loss at the spine in elderly postmenopausal women. Furthermore, women with the tt genetic variant of VDR appear to be at a greater risk for this deleterious effect of caffeine on bone. C1 Creighton Univ, Sch Med, Bone Metab Unit, Omaha, NE 68131 USA. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. Ryschon Hlth & Technol Serv, Valentine, NE USA. RP Rapuri, PB (reprint author), Creighton Univ, Sch Med, Bone Metab Unit, 601 N 30th St,Room 6718, Omaha, NE 68131 USA. FU NIA NIH HHS [UO1-AG10373, R01-AG10358] NR 41 TC 107 Z9 117 U1 2 U2 15 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2001 VL 74 IS 5 BP 694 EP 700 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 485TG UT WOS:000171779500023 PM 11684540 ER PT J AU Van Duyn, MAS Kristal, AR Dodd, K Campbell, MK Subar, AF Stables, G Nebeling, L Glanz, K AF Van Duyn, MAS Kristal, AR Dodd, K Campbell, MK Subar, AF Stables, G Nebeling, L Glanz, K TI Association of awareness, intrapersonal and interpersonal factors, and stage of dietary change with fruit and vegetable consumption: A national survey SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE health behavior; psychosocial; fruit and vegetables; diet surveys ID HEALTH BELIEF MODEL; CANCER PREVENTION; SOCIAL SUPPORT; FAT REDUCTION; ATTITUDES; NUTRITION; BEHAVIOR; INTERVENTIONS; KNOWLEDGE AB Purpose. To examine associations of awareness, intrapersonal and interpersonal factors, and stage of change with consumption of fruits and vegetables. Design. Nationally representative, random digit dial survey conducted in 1997 with a response rate of 44.5%. Psychosocial correlates of fruit and vegetable consumption were assessed using regression analyses. Setting. United States. Subjects. A total of 2605 adults who were 18 years and older. Measures. Awareness of the "5 A Day for Better Health" program and its message, along with stage of change; taste preferences; self-efficacy; and perceived benefits, barriers, threats, social support, and norms related to fruit and vegetable consumption. Results. Awareness and intrapersonal and interpersonal factors explained 24% of the variance in fruit and vegetable consumption beyond the 9% explained ly demographic characteristics. Knowledge of the 5 A Day message wa's associated with a 22% increase in fruit and vegetable consumption. Self-efficacy for eating fruits and vegetables and taste preferences (affect) were the factors most consistently and strongly associated with both higher consumption and higher likelihood of being in action or maintenance stages of change. Affect and perceived barriers were more strongly associated with increased vegetables and salad than fruit. Conclusions. Dietary intervention programs to increase fruit and vegetable consumption should emphasize the 5 A Day message, increased self-efficacy, and ways to make vegetables more palatable and easily accessible. Understanding the factors that influence dietary choices should be used when designing dietary interventions. C1 NCI, Off Commun, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. RP Van Duyn, MAS (reprint author), NCI, Off Commun, NIH, Bldg 31,Room 10A10, Bethesda, MD 20892 USA. OI Kristal, Alan/0000-0002-7329-1617 NR 52 TC 104 Z9 105 U1 1 U2 19 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD NOV-DEC PY 2001 VL 16 IS 2 BP 69 EP 78 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 494HV UT WOS:000172277100002 PM 11727591 ER PT J AU Tang, DC Prauner, R Liu, WL Kim, KH Hirsch, RP Driscoll, MC Rodgers, GP AF Tang, DC Prauner, R Liu, WL Kim, KH Hirsch, RP Driscoll, MC Rodgers, GP TI Polymorphisms within the angiotensinogen gene (GT-repeat) and the risk of stroke in pediatric patients with sickle cell disease: A case-control study SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE angiotensinogen; GT-repeat; stroke; sickle cell diseases ID HUMAN ESSENTIAL-HYPERTENSION; RELATIVE HYPERTENSION; INHIBITION; LINKAGE; LOCUS; MICE AB Stroke is one of the most devastating complications of patients with sickle cell disease (SCD). Currently, there are no known molecular or genetic markers that can be used to assess the risk of stroke in this population. We have previously shown that relative hypertension may be one risk factor for stroke in SCD. In a case-control study, we Investigated the association between GT-repeat polymorphism within the angiotensinogen (AGT) gene and the risk of stroke in pediatric patients with SCD. After informed consent was obtained, 63 patients (21 stroke subjects and 42 nonstroke control subjects matched according to age and sex) with SCD followed at local pediatric hematology clinics were genotyped to test the association of specific GT-repeat alleles of the AGT gene and occurrence of stroke. There were statistical differences in the distribution of the genotypes among stroke and nonstroke SCD patients (chi (2) = 10.82, df = 11, P < 0.05). We also found GT-repeat alleles A3 and/or A4 of the AGT gene conferred a four-fold increase in the risk of stroke (odds ratio [OR] = 4, P < 0.05). The attributable odds ratio for allele A3 and A4 is 2.24 and 4.33, respectively (P < 0.005). Our results suggest that GT-repeat within the AGT gene may be associated with risk of stroke in pediatric SCID. The relative risk of stroke in the presence of alleles A3 and/or A4 is fourfold greater than In the absence of these alleles. If these data are substantiated in a larger cohort of patients, our results indicate that the determination of GT-repeat of AGT gene may be a useful genetic marker to assess the risk for stroke of patients with SCD. Published 2001 Wiley-Liss, Inc.(dagger) C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Pediat, Washington, DC 20307 USA. George Washington Univ, Med Ctr, Dept Epidemiol & Stat, Washington, DC 20037 USA. Childrens Natl Med Ctr, Dept Hematol Oncol & Bone Marrow Transplantat, Washington, DC 20010 USA. RP Rodgers, GP (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N119, Bethesda, MD 20892 USA. NR 18 TC 19 Z9 20 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 2001 VL 68 IS 3 BP 164 EP 169 DI 10.1002/ajh.1173 PG 6 WC Hematology SC Hematology GA 482UM UT WOS:000171595700005 PM 11754397 ER PT J AU Huizing, M Anikster, Y Fitzpatrick, DL Jeong, AB D'Souza, M Rausche, M Toro, JR Kaiser-Kupfer, MI White, JG Gahl, WA AF Huizing, M Anikster, Y Fitzpatrick, DL Jeong, AB D'Souza, M Rausche, M Toro, JR Kaiser-Kupfer, MI White, JG Gahl, WA TI Hermansky-Pudlak syndrome type 3 in Ashkenazi Jews and other non-Puerto Rican patients with hypopigmentation and platelet storage-pool deficiency SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PROTEIN COMPLEX; OCULOCUTANEOUS ALBINISM; GRANULOMATOUS COLITIS; LOCUS HETEROGENEITY; PULMONARY FIBROSIS; VESICLE FORMATION; TYROSINASE GENE; HPS GENE; MUTATIONS; ADAPTER AB Hermansky-Pudlak syndrome (HPS), consisting of oculocutaneous albinism and a bleeding diathesis due to the absence of platelet dense granules, displays extensive locus heterogeneity. HPS1 mutations cause HPS-1 disease, and ADTB3A mutations cause HPS-2 disease, which is known to involve abnormal intracellular vesicle formation. A third HPS-causing gene, HPS3, was recently identified on the basis of homozygosity mapping of a genetic isolate of HPS in central Puerto Rico. We now describe the clinical and molecular characteristics of eight patients with HPS-3 who are of non-Puerto Rican heritage. Five are Ashkenazi Jews; three of these are homozygous for a 1303+1G -->A splice-site mutation that causes skipping of exon 5, deleting an RsaI restriction site and decreasing the amounts of mRNA found on northern blotting. The other two are heterozygous for the 1303+1G -->A mutation and for either an 1831+2T -->G or a 2621-2A -->G splicing mutation. Of 235 anonymous Ashkenazi Jewish DNA samples, one was heterozygous for the 1303+1G -->A mutation. One seven-year-old boy of German/Swiss extraction was compound heterozygous for a 2729+1G -->C mutation, causing skipping of exon 14, and resulting in a C1329T missense (R396W), with decreased mRNA production. A 15-year-old Irish/English boy was heterozygous for an 89-bp insertion between exons 16 and 17 resulting from abnormal splicing; his fibroblast HPS3 mRNA is normal in amount but is increased in size. A 12-year-old girl of Puerto Rican and Italian background has the 3,904-bp founder deletion from central Puerto Rico on one allele. All eight patients have mild symptoms of HPS; two Jewish patients had received the diagnosis of ocular, rather than oculocutaneous, albinism. These findings expand the molecular diagnosis of HPS, provide a screening method for a mutation common among Jews, and suggest that other patients with mild hypopigmentation and decreased vision should be examined for HPS. C1 NICHHD, NIH, Sect Human Biochem Genet, Heritable Disorders Branch, Bethesda, MD 20892 USA. NCI, NIH, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Clin Serv Branch, Bethesda, MD 20892 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. RP Gahl, WA (reprint author), NICHHD, NIH, Sect Human Biochem Genet, Heritable Disorders Branch, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9s-241, Bethesda, MD 20892 USA. NR 40 TC 54 Z9 56 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2001 VL 69 IS 5 BP 1022 EP 1032 DI 10.1086/324168 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 479PU UT WOS:000171413400010 PM 11590544 ER PT J AU Smith, MW Lautenberger, JA Shin, HD Chretien, JP Shrestha, S Gilbert, DA O'Brien, SJ AF Smith, MW Lautenberger, JA Shin, HD Chretien, JP Shrestha, S Gilbert, DA O'Brien, SJ TI Markers for mapping by admixture linkage disequilibrium in African American and Hispanic populations SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE SCAN; ADMIXED POPULATIONS; SUSCEPTIBILITY LOCUS; ETHNIC-DIFFERENCES; DNA-POLYMERASE; DISEASE RISK; GENES; MICROSATELLITES; PROPORTIONS; SELECTION AB Population linkage disequilibrium occurs as a consequence of mutation, selection, genetic drift, and population substructure produced by admixture of genetically distinct ethnic populations. African American and Hispanic ethnic groups have a history of significant gene flow among parent groups, which can be of value in affecting genome scans for disease-gene discovery in the case-control and transmission/disequilibrium test designs. Disease-gene discovery using mapping by admixture linkage disequilibrium (MALD) requires a map of polymorphic markers that differentiate between the founding populations, along with differences in disease-gene allele frequencies. We describe markers appropriate for MALD mapping by assessing allele frequencies of 744 short tandem repeats (STRs) in African Americans, Hispanics, European Americans, and Asians, by choosing STR markers that have large differences in composite delta, log-likelihood ratios, and/or I*(2) for MALD. Additional markers can be added to this MALD map by utilization of the rapidly growing single-nucleotide-polymorphism databases and the literature, to achieve a 3-10-cM scanning scale. The map will be useful for studies of diseases, including prostate and breast cancer, diabetes, hypertension, and end-stage renal disease, that have large differences in incidence between the founding populations of either Hispanics or African Americans. C1 NCI, Intramural Res Support Program, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Welsh Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. Celera Genom, Foster City, CA USA. RP Smith, MW (reprint author), NCI, Intramural Res Support Program, Sci Applicat Int Corp Frederick, POB B,7th St Extens, Frederick, MD 21702 USA. RI Smith, Michael/B-5341-2012 FU NCI NIH HHS [N01-CO-56000] NR 49 TC 108 Z9 112 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2001 VL 69 IS 5 BP 1080 EP 1094 DI 10.1086/323922 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 479PU UT WOS:000171413400016 PM 11590548 ER PT J AU Zahm, SH Blair, A AF Zahm, SH Blair, A TI Assessing the feasibility of epidemiologic research on migrant and seasonal farmworkers: An overview SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Editorial Material ID CANCER C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Zahm, SH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8074, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015 NR 18 TC 15 Z9 15 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 487 EP 489 DI 10.1002/ajim.10006 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900001 PM 11675617 ER PT J AU Zahm, SH Colt, JS Engel, LS Keifer, MC Alvarado, AJ Burau, K Butterfield, P Caldera, S Cooper, SP Garcia, D Hanis, C Hendrikson, E Heyer, N Hunt, LM Krauska, M MacNaughton, N McDonnell, CJ Mills, PK Mull, LD Nordstrom, DL Outterson, B Slesinger, DP Smith, MA Stallones, L Stephens, C Sweeney, A Sweitzer, K Veron, SW Blair, A AF Zahm, SH Colt, JS Engel, LS Keifer, MC Alvarado, AJ Burau, K Butterfield, P Caldera, S Cooper, SP Garcia, D Hanis, C Hendrikson, E Heyer, N Hunt, LM Krauska, M MacNaughton, N McDonnell, CJ Mills, PK Mull, LD Nordstrom, DL Outterson, B Slesinger, DP Smith, MA Stallones, L Stephens, C Sweeney, A Sweitzer, K Veron, SW Blair, A TI Development of a life events/icon calendar questionnaire to ascertain occupational histories and other characteristics of migrant farmworkers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE farmworkers; agricultural; occupation; questionnaire design; epidemiology; migrant; Hispanic ID CANCER; HISPANICS; HEALTH; ACCULTURATION; FEASIBILITY; WORKERS; LATINO; WHITES; WOMEN AB Background Specialized methods are necessary to collect data from migrant farm-workers for epidemiologic research. Methods We developed a questionnaire that collected lifetime occupational histories and other lifestyle risk factors via a life events/icon calendar; and administered the questionnaire to a convenience sample of 162 migrant farmworkers in nine areas of the U.S. Results The average duration of the interviews was about 1 h 30 min, with an average of 45 min for the work history section. The occupational histories covered a median of 27.6 years per person for men and 20.8 years per person for women. The median number of years spent in farm jobs was 11.3 for men and 5.8 for women. Thc median number of farm jobs (crop/task combination) per person was 59 among men and 27 among women. Many farmworkers performed the same crop/task combinations at multiple times throughout their lives, yielding a median of 13 unique farm jobs and 8 unique crops among men and 7 jobs and 5 crops among women. Conclusions The project demonstrated that it is feasible to collect detailed work histories and other risk factor data from farmworkers, documented the complexity of work histories encountered among farmworkers, and yielded recommendations for refining a questionnaire that will facilitate future epidemiologic research on farmworkers. (C) 2001 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Calif State Univ Fresno, Fresno, CA 93740 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Montana State Univ, Bozeman, MT 59717 USA. Migrant Clinicians Network, Austin, TX USA. Plan Salud Valle, Longmont, CO USA. Univ Texas, Sch Nursing, San Antonio, TX 78285 USA. La Clin, Wild Rose, WI USA. SRA Technol Inc, Falls Church, VA USA. Canc Registry Cent Calif, Fresno, CA USA. Assoc Farmworker Opportun Programs, Arlington, VA USA. Marshfield Med Res Fdn, Marshfield, WI 54449 USA. Univ Wisconsin, Madison, WI USA. Colorado State Univ, Ft Collins, CO 80523 USA. Montana Migrant Council Inc, Billings, MT USA. RP Zahm, SH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8074, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015 NR 28 TC 21 Z9 21 U1 2 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 490 EP 501 DI 10.1002/ajim.1117 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900002 PM 11675618 ER PT J AU Engel, LS Keifer, MC Zahm, SH AF Engel, LS Keifer, MC Zahm, SH TI Comparison of a traditional questionnaire with an icon/calendar-based questionnaire to assess occupational history SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE icon; calendar; questionnaire; occupational history; recall; memory aids ID BREAST-CANCER; WOMEN AB Background Self-reported work histories are an essential tool for estimating exposure in many occupational epidemiologic studies. However, the transience of some occupations such as farm work can hamper recall, resulting in inaccurate reporting. To address this problem, we have developed an icon/calendar-based questionnaire. This study compares work histories collected via this questionnaire to those collected via a traditional questionnaire. Methods Eighty-nine farmworkers and non-farmworkers were interviewed twice, 8-10 months apart, about their lifetime employment. In the first interview, subjects were asked to recount their entire work history, starting from the interview date and moving backwards in time ("traditional questionnaire"). In the second interview, subjects were first asked about important life events, which were recorded with icons on a calendar They were then asked to recount their work history, which was recorded, job-by-job, on the calendar with icons ("icon-calendar questionnaire"). Results Number of jobs and amount of work time accounted for since first employment were significantly greater using the icon-calendar questionnaire than the traditional questionnaire, the disparity increasing with time from the date of interview. The ratio of number of jobs in the traditional questionnaire to number of jobs in the icon-calendar questionnaire decreased from 100.0% in the most recent time period to 0.0% in the earliest time period. While the percentage of time explained by employment remained relatively constant across time periods in the icon-calendar questionnaire, ranging from 86.3 to 98.9%, it rapidly decreased with time in the traditional questionnaire, from 77.9% in the most recent time period to 0.0% in the earliest time period. Conclusions The icon-calendar questionnaire was more effective than the traditional questionnaire for obtaining complex work histories during interviews, producing a more complete picture of a person's work history. published 2001 Wiley-Liss, Inc. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Pacific NW Agr Safety & Hlth Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Med, Occupat Med Program, Seattle, WA 98195 USA. Univ Washington, Dept Environm Hlth, Occupat Med Program, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Engel, LS (reprint author), NCI, Occupat Epidemiol Branch, 6120 Execut Blvd,Room 8113, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015 FU NIEHS NIH HHS [ES07262]; PHS HHS [QTR50104, U07/CCU012926-02] NR 12 TC 30 Z9 30 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 502 EP 511 DI 10.1002/ajim.1118.abs PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900003 PM 11675619 ER PT J AU Engel, LS Keifer, MC Thompson, ML Zahm, SH AF Engel, LS Keifer, MC Thompson, ML Zahm, SH TI Test-retest reliability of an icon/calendar-based questionnaire used to assess occupational history SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE icon; calendar; questionnaire; occupational history; recall; memory aids; farmwork ID FOOD-FREQUENCY QUESTIONNAIRE; WORK HISTORIES; VALIDITY; INTERVIEW; REPRODUCIBILITY; VALIDATION; COHORT AB Background Self-reported work histories can be critical for both epidemiologic and clinical purposes. However; the complexity of some work histories, such as those of migrant farm workers, can hamper recall, resulting in inaccurate reporting. Memory aids may reduce such error This study, assesses the reliability of work histories collected using such aids in the form of an icon/calendar-based questionnaire. Methods Thirty-one males engaged in farmwork and other manual labor for a median 28 years (range: 10-64) were interviewed twice, 8-14 months apart, about their lifetime employment. In each interview, subjects were asked about important life events, which were recorded with icons on a calendar They were then asked to recount their work history, including for each job the tasks, crops or products handled, starting and ending dates, and location. This information was recorded, job-by-job, on the calendar with icons. Results Interquestionnaire agreement of cumulative reported employment duration (as measured by, the correlation coefficient) was moderate to high across all time periods for certain crops (e.g., r = 0.69-0.92 for apple-related work), by location (e.g., r = 0.76-0.95 for Washington State), and for agricultural work in general (r = 0.67-0.94), but was lower for specific tasks. Agreement of job counts was high for total work history for certain crops (e.g., r = 0.93 for apple-related work), by location (e.g., r = 0.90 for Washington State), and for agricultural work in general (r = 0.89), but paradoxically decreased with proximity to the interview date. Agreement of both measures tended to be highest for those tasks and crops in which subjects reported spending the most time. Categorization of subjects into tertiles on the basis of either cumulative duration or counts produced results similar to those observed for job counts. Conclusions The icon-calendar questionnaire is an effective tool for estimating cumulative duration of certain work categorizations among subjects with complex work histories. Published 2001 Wiley-Liss, Inc. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Pacific NW Agr Safety & Hlth Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Med, Occupat Med Program, Seattle, WA 98195 USA. Univ Washington, Dept Environm Hlth, Occupat Med Program, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Engel, LS (reprint author), NCI, Occupat Epidemiol Branch, 6120 Execut Blvd,Room 8113, Bethesda, MD 20892 USA. FU NIEHS NIH HHS [ES07262]; PHS HHS [QTR50104, U07/CCU012926-02] NR 21 TC 12 Z9 12 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 512 EP 522 DI 10.1002/ajim.1119 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900004 PM 11675620 ER PT J AU Colt, JS Engel, LS Keifer, MC Thompson, ML Zahm, SH AF Colt, JS Engel, LS Keifer, MC Thompson, ML Zahm, SH TI Comparability of data obtained from migrant farmworkers and their spouses on occupational history SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE migrant farmworkers; proxy respondents; epidemiologic methods; occupational history; questionnaire; agriculture ID PROXY RESPONDENTS; SURROGATE RESPONDENTS; PESTICIDE USE; VALIDITY; EXPOSURE; ACCURACY; INFORMATION; VALIDATION; INTERVIEW; FARMERS AB Background Epidemiologic studies, particularly case-control studies, often rely on proxy respondents to provide information about subjects' occupational histories. The quality of proxy-reported information in occupational histories has never been evaluated for migrant farmworkers. Methods We compared occupational histories self-reported by 31 farmworkers with those reported by their wives. Vie work histories were obtained using an icon/calendar-based questionnaire that was designed to facilitate recall for migrant farmworkers, who typically have complex work histories. Results The work histories provided by proxy respondents contained 32% fewer jobs and accounted for 24% fewer years than the self-reported histories. Correlations for lifetime duration of employment in different types of jobs were moderate to good for general agricultural jobs in Washington (0.70) and apple-related jobs (0.65), which were held by virtually all of the farmworkers; correlations were moderate to poor for less common jobs and for specific types of tasks. Agreement was better after marriage than before, and for jobs held in the current year compared to other time frames. Overall, the ability of the spouses to provide occupational histories for farmworkers was within the range observed in studies involving other occupations and industries. Conclusions In studies involving farmworkers, when study subjects cannot be interviewed, spouses cat? provide useful information on occupational histories. However, the information should be used only for more generalized exposure assessments; it is most appropriate for estimating cumulative duration of agricultural work, or recent work, by place or for common crops. (C) 2001 Wiley-Liss, Inc. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Occupat Med Program, Seattle, WA 98195 USA. Univ Washington, Dept Environm Hlth, Occupat Med Program, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Colt, JS (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8112, Bethesda, MD 20892 USA. NR 19 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 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 523 EP 530 DI 10.1002/ajim.1120 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900005 PM 11675621 ER PT J AU Cooper, SP Darragh, AR Vernon, SW Stallones, L MacNaughton, N Robison, T Hanis, C Zahm, SH AF Cooper, SP Darragh, AR Vernon, SW Stallones, L MacNaughton, N Robison, T Hanis, C Zahm, SH TI Ascertainment of pesticide exposures of migrant and seasonal farmworker children: Findings from focus groups SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE farmwork; migrant; pesticides; cancer; childhood; Hispanic; Texas; Colorado ID CANCER AB Background To design questionnaires for epidemiologic research among children of migrant farmworkers, researchers need to consider ways to best solicit information about pesticide exposures. Methods Bilingual facilitators conducted five focus groups with either migrant farmworker mothers or their children (age range 8-16 years) in southern Texas and northeastern Colorado. Guided questions were used to assess activities of migrant farmworker children and the ways to best elicit information about exposure to pesticides. Results Participants reported a large number of activities that may potentially expose children to pesticides through both direct and indirect routes. Prompting, indirect questions about chemical use, and use of local and trusted facilitators increased information elicited from focus group participants. Conclusions These focus groups helped to provide information for developing questionnaire items related to pesticide exposure among migrant farmworker children, and highlighted the importance of using bilingual community interviewers and including children as respondents. (C) 2001 Wiley-Liss, Inc. C1 Univ Texas, Sch Publ Hlth, Houston, TX 77225 USA. Univ Sacred Heart, Fairfield, CT USA. Colorado State Univ, Ft Collins, CO 80523 USA. NCI, Bethesda, MD 20892 USA. RP Cooper, SP (reprint author), Univ Texas, Sch Publ Hlth, POB 20186, Houston, TX 77225 USA. RI Darragh, Amy/E-2946-2011; Zahm, Shelia/B-5025-2015 NR 15 TC 16 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 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 531 EP 537 DI 10.1002/ajim.10009 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900006 PM 11675622 ER PT J AU Ward, MH Prince, JR Stewart, PA Zahm, SH AF Ward, MH Prince, JR Stewart, PA Zahm, SH TI Determining the probability of pesticide exposures among migrant farmworkers: Results from a feasibility study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE agriculture; migrant workers; pesticides; exposure assessment ID WORKERS; CANCER AB Background Migrant and seasonal farmworkers are exposed to pesticides through their work with crops and livestock. Because workers are usually unaware of the pesticides applied, specific pesticide exposures cannot be determined by interviews. We conducted a study to determine the feasibility of identifying probable pesticide exposures based on work histories. Methods The study included 162 farm workers in seven states. Interviews obtained a lifetime work history including the crops, tasks, months, and locations worked. We investigated the availability of sun,ey data oil pesticide use for crops and livestock in the seven pilot states. Probabilities of use for pesticide types (herbicides, insecticides, fungicides, etc.) and specific chemicals were calculated from the available data for two farm workers. The work histories were chosen to illustrate how the quality of the pesticide use information varied across crops, states, and years. Results For most vegetable and fruit crops there were regional pesticide use data ill the late 1970s, no data in the 1980s, and state-specific data every other year in the 1990s. Annual use surveys for cotton and potatoes began in the late 1980s. For a few crops, including asparagus, broccoli, lettuce, strawberries, plums, and Christmas trees, there were no federal data or data from the seven states before the 1990s. Conclusions We conclude that identifying probable pesticide exposures is feasible ill some locations. However, the lack of pesticide use data before the 1990s for many crops will limit the quality of historic exposure assessment for most workers. Published 2001 Wiley-Liss, Inc. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Ward, MH (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPN-8104, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015 NR 67 TC 11 Z9 11 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 538 EP 553 DI 10.1002/ajim.1121.abs PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900007 PM 11675623 ER PT J AU Hernandez-Valero, MA Bondy, ML Spitz, MR Zahm, SH AF Hernandez-Valero, MA Bondy, ML Spitz, MR Zahm, SH TI Evaluation of Mexican American migrant farmworker work practices and organochlorine pesticide metabolites SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE agriculture; migrant farmworkers; Mexican-Americans; adults; Texas; serum levels; organochlorine pesticides; work practices; living conditions; pesticide exposures ID BREAST-CANCER; RISK; LYMPHOMA AB Background Epidemiologic studies often must rely upon questionnaire data to assess past exposures. The ability of questionnaires to rank migrant farmworkers according to past pesticide exposure is not known. Methods We conducted a pilot feasibility, study to measure a panel of 21 organochlorine pesticides (OCPs) and correlate levels with reported occupational exposures in 26 Mexican-American migrant farmworkers in Baytown, Texas. The Migrant Farmworker Questionnaire developed by the National Cancer Institute (NCI) was administered and each participant donated a blood sample. Three OCPs [mean (ppb) levels: mirex 1.8, DDT 1.0, and trans-nonachlor 0.7] were detected despite the fact that these chemicals have been banned in the US for many years, and the detected levels were far higher than the standard provided by, the referent laboratory. Work clothes, protective attire, and self-reported pesticide exposures were significant predictors of OCP exposure. Similarly, personal hygiene, length of employment, and number of duties also predicted OCP exposure. Conclusions The results of this study indicate that data obtained from standardized questionnaires may be reasonable indicators of occupational exposure when biomarker data are not available. (C) 2001 Wiley-Liss, Inc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. NCI, Div, Rockville, MD USA. RP Hernandez-Valero, MA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, 1515 Holcombe Blvd,Box 536, Houston, TX 77030 USA. RI Zahm, Shelia/B-5025-2015 FU NCI NIH HHS [R01 CA55769] NR 15 TC 20 Z9 20 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 554 EP 560 DI 10.1002/ajim.10008 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900008 PM 11675624 ER PT J AU Stewart, PA Prince, JK Colt, JS Ward, MH AF Stewart, PA Prince, JK Colt, JS Ward, MH TI A method for assessing occupational pesticide exposures of farmworkers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE agriculture; migrant workers; pesticides; exposure assessment ID DERMAL EXPOSURE; CAPTAN; AZINPHOSMETHYL; CALIFORNIA; HARVESTERS; RESIDUES; WORKERS AB Background The health of farmworkers as related to pesticide exposure is of concern but assessing exposures for epidemiologic studies requires different techniques than approaches used for studies of industrial workers. Methods A review of the literature identified possible factors that affect exposure intensity. A model was developed to estimate an exposure score. Exposures in the literature were estimated using the model and compared to the measurements in the literature. Results Three studies were found with information appropriate for evaluation of the model. There was a statistical difference between the means of the scores corresponding to above and below the median of the measurements. The correlation coefficient between the scores and the measurements from the literature was 0.77. Conclusions Although the evaluation was limited, the model appeared to work well, but more testing is needed. More research is also needed to increase understanding of what affects the exposures of these workers. Published 2001 Wiley-Liss, Inc. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Stewart, PA (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, EPS 8102,6120 Execut Blvd MSC 7240, Bethesda, MD 20892 USA. NR 41 TC 17 Z9 17 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 561 EP 570 DI 10.1002/ajim.1122 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900009 PM 11675625 ER PT J AU Mills, PK Zahm, SH AF Mills, PK Zahm, SH TI Organophosphate pesticide residues in urine of farmworkers and their children in Fresno County, California SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article ID AGRICULTURAL RISK-FACTORS; EXPOSURE; METABOLITES; MINNESOTA; WORKERS; CANCER; IOWA; MEN AB Background Childhood cancer, notably leukemia, brain cancer, non-Hodgkin's lymphoma, soft tissue sarcoma, and Hodgkin's disease, has been associated with pesticide exposure, often with greater relative risks than among exposed adults, suggesting greater susceptibility, in children. These differences in risk may be due to developmental factors or differences in pesticide exposure. Methods A feasibility, study was conducted to determine levels of pesticide metabolites in urine of adults (n = 18) and children (n = 9) in Fresno County, California, an intensely agricultural county in the Central San Joaquin Valley. Spot urine samples were obtained and analyzed for six metabolites of organophosphate (OP) pesticides using gas chromatography with flame photometric detection methods. The metabolites of OP pesticides included DMP, DEP, DMTP, DMDTP, DETP, and DEDTP. Results Levels were generally low for both adults and children for most metabolites tested. Frequencies of detection ranged from 0 to 37%, with mean levels ranging from non-detectable to 13.22 pph. However levels of several metabolites were higher in children than in adults. The most frequently, detected metabolite, DMP, was found among 44% of the children and 33% of the adults. DMTP was detected among 33% of the children and 28% of the adults. Conclusions These results are difficult to interpret given the sampling variation associated with the small sample size. Nevertheless, because OP pesticides have been associated with increased cancer risk in animal and human studies, these results indicate a need to closely monitor children's exposure to environmental chemicals. (C) 2001 Wiley-Liss, Inc. C1 Canc Registry Cent Florida, Fresno, CA 93710 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Mills, PK (reprint author), Canc Registry Cent Florida, 1320 E Shaw Ave,Suite 160, Fresno, CA 93710 USA. RI Zahm, Shelia/B-5025-2015 NR 28 TC 36 Z9 38 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 571 EP 577 DI 10.1002/ajim.10007 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900010 PM 11675626 ER PT J AU Cooper, SP Burau, K Sweeney, A Robison, T Smith, MA Symanski, E Colt, JS Laseter, J Zahm, SH AF Cooper, SP Burau, K Sweeney, A Robison, T Smith, MA Symanski, E Colt, JS Laseter, J Zahm, SH TI Prenatal exposure to pesticides: A feasibility study among migrant and seasonal farmworkers SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE prenatal; farmwork; migrant; pesticides; cancer; occupation; Hispanic; Texas ID VOLATILE ORGANIC-COMPOUNDS; MATERNAL ADIPOSE-TISSUE; CORD-BLOOD; POLYCHLORINATED-BIPHENYLS; REFERENCE RANGE; MILK; PLACENTA; RESIDUES; HAZARDS; MOTHERS AB Background Migrant and seasonal farmworkers have a high potential for pesticide exposures, yet are rarely included in epidemiologic studies. This study examined the feasibility of assessing prenatal exposures to pesticides and other compounds in pregnant Hispanic farmworkers. Methods Nine women completed a survey about work experiences during pregnancy. Maternal urine, cord blood, and placenta samples were obtained at delivery for analysis of 51 analytes, including 6 phenoxy acid or triazine herbicides, 21 organochlorine insecticides, 10 PCBs, and 14 volatile organic compounds. Results Seven of 51 analytes were found in the biological samples. DDE, DDT dichlorbenzene, toluene, trimethylbenzene, and endosulfan sulfate were detected ill cord blood samples, and 2,4-D in urine from one or more women. Conclusions We documented the feasibility of following farmworkers to assess in utero exposure to pesticides and other contaminants, and demonstrated exposure to these compounds. Difficulties in measuring pesticides with short half lives were noted. (C) 2001 Wiley-Liss, Inc. C1 Univ Texas, Sch Publ Hlth, Houston, TX 77030 USA. Accu Chem Labs, Richardson, TX USA. NCI, Bethesda, MD 20892 USA. RP Cooper, SP (reprint author), Univ Texas, Sch Publ Hlth, POB 20186, Houston, TX 77030 USA. RI Zahm, Shelia/B-5025-2015 NR 45 TC 18 Z9 19 U1 2 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 578 EP 585 DI 10.1002/ajim.1123 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900011 PM 11675627 ER PT J AU Cooper, SP Burau, K Hanis, C Henry, J MacNaughton, N Robinson, T Smith, MA Sweeney, A Vernon, SW Zahm, SH AF Cooper, SP Burau, K Hanis, C Henry, J MacNaughton, N Robinson, T Smith, MA Sweeney, A Vernon, SW Zahm, SH TI Tracing migrant farmworkers in Starr County, Texas SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE farmwork; migrant; pesticides; cancer; occupation; Hispanic; Texas ID CANCER; HEALTH AB Background In response to The National Cancer Institute (NCI) concerns about the ability to conduct studies among migrant farmworkers, this study evaluated the feasibility of identifying migrant farmworkers in their home state and tracing them over an extended period of time. Methods In 1995, a group of 196 persons who had classified themselves as "migrant farmworkers" in two earlier chronic disease studies was identified. The primary objective of the current study was to determine the proportion of these farmworkers who could be located in 1995-1996. Results Of these farmworkers, 163 were located and were living (83.2%), 15 had died (7.6%), and 18 (9.2%) were lost to follow-up. Conclusions The excellent follow-up rate was due in part to the high participation rates among persons contacted for information, stability of the farmworker's permanent homes predictable timing of migration, and a longstanding health research program with established community contacts. (C) 2001 Wiley-Liss, Inc. C1 Univ Texas, Sch Publ Hlth, Houston, TX 77225 USA. NCI, Bethesda, MD 20892 USA. RP Cooper, SP (reprint author), Univ Texas, Sch Publ Hlth, POB 20186, Houston, TX 77225 USA. RI Zahm, Shelia/B-5025-2015 NR 11 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 586 EP 591 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900012 PM 11675628 ER PT J AU Nordstrom, DL Krauska, M DeStefano, F Colt, JS Zahm, SH AF Nordstrom, DL Krauska, M DeStefano, F Colt, JS Zahm, SH TI Ability to trace migrant farmworkers ten years after initial identification in a northern state (Wisconsin) SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE data collection; cohort studies; tracing; migrants; Mexican-Americans; agriculture; Wisconsin; Texas AB Background Migrant farmworkers have rarely been included in epidemiologic studies. To assess the feasibility of following farmworkers, over extended periods, a critical feature of many study designs, we attempted to trace a sample of Mexican-American farmworkers identified in a clinic in Wisconsin. Methods We randomly chose 100 farmworkers from a migrant health center registration list for 1984-85. In 1995, we searched recent clinic records, made telephone calls, and visited migrant camps to find these farmworkers in Wisconsin during the growing season. We also attempted to find 46 farmworkers at their homes in southwest Texas over a two-week period in 1996 using the address listed in the clinic records, local phone books, and conversations with next-door neighbors. Results Although 25 farmworkers had reregistered at the clinic in recent years, we found only 6 of them in Wisconsin in 1995. In southwest Texas, we either located or ascertained information about the vital status of 25 of the 46 farmworkers (54%). Conclusions Tracing efforts must include extensive contacts in farmworkers home states and must incorporate a variety of information sources. Tracing farmworkers in epidemiologic studies appears to be feasible but requires more intensive methods over longer periods of time than those used in this study. (C) 2001 Wiley-Liss, Inc. C1 Marshfield Clin Fdn Med Res & Educ, Dept Epidemiol & Biostat, Marshfield, WI 54449 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Nordstrom, DL (reprint author), State Dept Hlth & Family Serv, Wisconsin Div Publ Hlth, 1 W,Wilson St,Rm 218, Madison, WI 53703 USA. NR 10 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 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 592 EP 595 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900013 PM 11675629 ER PT J AU Colt, JS Stallones, L Cameron, LL Dosemeci, M Zahm, SH AF Colt, JS Stallones, L Cameron, LL Dosemeci, M Zahm, SH TI Proportionate mortality among US migrant and seasonal farmworkers in twenty-four states SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE agriculture; cancer; epidemiology; farmworker; migrant; mortality; occupation; pesticides ID CHRONIC NEUROLOGICAL SEQUELAE; GASTRIC-CANCER; EPIDEMIOLOGY; FARMERS; SUICIDE; WORKERS; HEALTH AB Background US migrant and seasonal farmworkers may be exposed to potentially carcinogenic pesticides and other agents. Little epidemiologic research has been conducted on this population. Methods We examined the proportionate mortality of 26,148 subjects (14,631 white men (WM),7,299 nonwhite men (NM), 1,081 white women (WW), and 3,137 nonwhite women (NW)) who were identified as farmworkers on death certificates from 24 US states during 1984-1993. Results Farmworkers had significantly elevated proportionate mortality from injuries, tuberculosis, mental disorders, cerebrovascular disease, respiratory diseases, ulcers, hypertension (NW), and cirrhosis (NW). There was significantly reduced mortality, from infectious diseases (other than tuberculosis), endocrine disorders, nervous system diseases, pneumoconioses, arteriosclerotic heart disease (WM), and all cancers combined. Proportionate cancer mortality analyses found excess cancers of the buccal cavity, larynx, esophagus, stomach, skin (NW), and cen,ix, and deficits for cancers of the colon, breast, kidney, pancreas (NW), and lymphohematopoietic system. Conclusions The excess deaths from injuries, respiratory disease, and stomach cancer, and the deficits of colon cancer and arteriosclerotic heart disease among farmworkers, are consistent with typical mortality patterns previously observed among farm owner/ operators. The excess buccal, laryngeal, esophageal, and cervical cancers, and the deficits of breast cancer and lymphohematopoietic cancers have not generally been observed in studies of farm owner/operators. Am. J. Ind. Med. 40:604-611, 2001. Published 2001 Wiley-Liss, Inc.(dagger) C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Colorado State Univ, Dept Environm Hlth, Ft Collins, CO 80523 USA. NIOSH, Illness Effects Sect, Surveillance Branch, Cincinnati, OH 45226 USA. RP Colt, JS (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8112, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015 NR 20 TC 27 Z9 28 U1 2 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 604 EP 611 DI 10.1002/ajim.1126 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900015 PM 11675631 ER PT J AU Mull, LD Engel, LS Outterson, B Zahm, SH AF Mull, LD Engel, LS Outterson, B Zahm, SH TI National farmworker database: Establishing a farmworker cohort for epidemiologic research SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE farmworker; epidemiology; prospective; cohort ID AGRICULTURE; OCCUPATION; WORKERS; RISK AB Background There is little research into the long-term health effects of pesticides and other agricultural exposures among seasonal and migrant farmworkers in the United States. We present results of a feasibility study that established a cohort of farmworkers for use in epidemiologic research. Methods Subjects consisted of migrant and seasonal farmworkers who joined the cohort while seeking social sen,ices through inembers of the Association of Farmworker Opportunity Programs (AFOP) and were entered in the National Farmworker Database (NFD) between the end of 1997 and March 1999. Uc designed an add-on interview with information that enhanced the utility of the database for epidemiologic research. Results We recruited and obtained basic demographic and employment information on 5,597 farmworkers at very modest cost and effort. Subjects were mostly seasonal (61.5%), female (56.7%), and Hispanic (67.4%), with a median age of 27. Most (62.6%) had not completed high school; almost all (99.1%) reported being U.S. citizens or permanent residents, an eligibility requirement for some of the sen,ices provided by AFOP. The majority (62.5%) had engaged in farmwork for less than 10 years, but had performed a wide variety of tasks on different crops, including row crops and tree fruits. Picking was the most common task reported. Most subjects had performed farmwork in Florida, North Carolina, Texas, Michigan, or Georgia. For usual source of health care, 63.7% reported use of U.S. hospitals or emergency rooms/clinics, 42.0% U.S. private physicians, and 29.7% migrant health clinics. Among subjects reporting a prior diagnosis of cancer, primary sources of health care for treatment of that cancer included U.S. private physicians (61.9%), U.S. hospitals or emergency rooms/clinics (23.8%), and migrant health clinics (10.5%). Conclusions Results suggest that by, adding a brief interview to the existing NFD data collection process, which was designed for other purposes, it is feasible to create all efficient tool for conducting longitudinal epidemiologic research among farmworkers. Am. J. Ind. Med. 40:612-618, 2001. (C) 2001 Wiley-Liss, Inc. C1 Assoc Farmworker Opportun Programs, Arlington, VA USA. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. RP Mull, LD (reprint author), Int Initiat End Child Labor, 1016 S Wayne St,Suite 702, Arlington, VA 22204 USA. RI Zahm, Shelia/B-5025-2015 NR 25 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2001 VL 40 IS 5 BP 612 EP 618 DI 10.1002/ajim.10016 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 490QQ UT WOS:000172062900016 PM 11675632 ER PT J AU Mandal, DM Wilson, AF Bailey-Wilson, JE AF Mandal, DM Wilson, AF Bailey-Wilson, JE TI Effects of misspecification of allele frequencies on the power of Haseman-Elston sib-pair linkage method for quantitative traits SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE quantitative trait; GASP; SAGE; Haseman-Elston sib-pair method; computer simulation; power study in linkage analysis ID SAMPLES; LOCUS AB It is well known that the Haseman-Elston (H-E) sib-pair linkage method does not assume that the genetic model underlying the trait phenotype is known without error, although this assumption is made for marker loci. However, misspecification of allele frequencies at the marker locus decreases power when some or all parental genotypes are unknown. In this study, the power of the H-E sib-pair method was compared for different types of traits when some or all parental data were missing and allele frequencies at the marker loci were misspecified. Data were generated for a quantitative trait and marker loci in nuclear families using G.A.S.P. (V3.3). Three types of traits were simulated with two equifrequent alleles with a random environmental effect (10%, 30%, and 50%). The simulated data were analyzed using (i) one of the parent's marker data, and (ii) no parental marker data, with both correct and incorrect marker allele frequencies. This test is found to be robust in most of the situations considered except for a slight decrease in power when sample size is small and when the marker locus is not very polymorphic. Published 2001 Wiley-Liss, Inc.(dagger). C1 NHGRI, NIH, Baltimore, MD 21224 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA USA. RP Bailey-Wilson, JE (reprint author), NHGRI, NIH, 333 Cassell Dr,Suite 2000, Baltimore, MD 21224 USA. RI Wilson, Alexander/C-2320-2009; OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCRR NIH HHS [1P41 RR 03655] NR 17 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 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 1 PY 2001 VL 103 IS 4 BP 308 EP 313 DI 10.1002/ajmg.1566 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 485KB UT WOS:000171752600008 PM 11746011 ER PT J AU Ng, D Mowrey, P Ragoussis, J Mirza, G Coll, E Di Fazio, MP Turner, C Levin, SW AF Ng, D Mowrey, P Ragoussis, J Mirza, G Coll, E Di Fazio, MP Turner, C Levin, SW TI Molecularly defined interstitial tandem duplication 6p case with mild manifestations SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE pure 6p duplication; FISH; developmental delay ID DELETION SYNDROME; REGION; MAP AB An interstitial tandem duplication of 6p21.1-p22.2 was found in a girl at 11 months of age when she was evaluated for developmental delay. Previous cases reported with partial 6p duplication usually have involved terminal duplications, with breakpoints ranging from 6p11 to 6p25. Our patient exhibits a milder phenotype compared to the previously reported cases in the literature. Features that she has in common with the other cases include craniofacial anomalies, such as broad nasal bridge and bulbous tip, thin lips, incomplete development of the scapha helix bilaterally, mild spastic paraparesis of the lower extremities, gross motor delay, and mild cognitive delays. (C) 2001 Wiley-Liss, Inc. C1 Walter Reed Army Med Ctr, Dept Pediat, Genet Sect, Washington, DC 20307 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. LabCorp, Dept Cytogenet, Res Triangle Pk, NC USA. Walter Reed Army Med Ctr, Dept Neurol, Washington, DC 20307 USA. Kings Coll London, GKT Med Sch, Div Med Mol Genet, London WC2R 2LS, England. RP Levin, SW (reprint author), Walter Reed Army Med Ctr, Dept Pediat, Genet Sect, Bldg 41, Washington, DC 20307 USA. EM sondra.levin@na.amedd.army.mil NR 12 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 1 PY 2001 VL 103 IS 4 BP 320 EP 325 DI 10.1002/1096-8628(20011101)103:4<320::AID-AJMG1577>3.3.CO;2-A PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 485KB UT WOS:000171752600010 PM 11746013 ER PT J AU Levy, LM AF Levy, LM TI Functional MR Imaging evaluation of spinal cord function by use of neurophysiologic stimuli SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material C1 NINCDS, NIH, Bethesda, MD 20892 USA. RP Levy, LM (reprint author), NINCDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 2001 VL 22 IS 10 BP 1811 EP 1812 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 532JV UT WOS:000174472100003 PM 11733307 ER PT J AU Naccasha, N Gervasi, MT Chaiworapongsa, T Berman, S Yoon, BH Maymon, E Romero, R AF Naccasha, N Gervasi, MT Chaiworapongsa, T Berman, S Yoon, BH Maymon, E Romero, R TI Phenotypic and metabolic characteristics of monocytes and granulocytes in normal pregnancy and maternal infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2001 CL RENO, NEVADA SP Soc Maternal Fetal Med DE leukocytes; normal pregnancy; infection; pyelonephritis; flow cytometry; neutrophils; monocytes ID WHOLE-BLOOD; ACTIVATION; LEUKOCYTES; PYELONEPHRITIS; PREECLAMPSIA; NEUTROPHIL; EXPRESSION; SEPSIS AB OBJECTIVE: Normal pregnancy has been proposed to be a state of physiologic activation of the innate limb of the immune response. Recent studies have concluded that normal pregnancy produces inflammatory changes in peripheral blood leukocytes akin to those of sepsis. This unexpected observation has implications that are critical to understanding the susceptibility of pregnant women to sepsis, the pathophysiology of preeclampsia, and the biology of normal pregnancy. This study was designed to examine the phenotypic and metabolic characteristics of monocytes and granulocytes in normal pregnancy and in pregnant patients with acute infection. STUDY DESIGN: A cross-sectional study was conducted that included nonpregnant women (n = 20), normal pregnant women (n = 57), and pregnant women with a positive blood culture and/or pyelonephritis (n = 16). Phenotypic and metabolic characteristics of monocytes and granulocytes were studied with the use of flow cytometry and monoclonal antibodies against surface markers (CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR). Intracellular reactive oxygen species were measured at basal conditions and after stimulation (oxidative burst). The stimulation index (ratio of intracellular reactive oxygen species after oxidative burst over basal state) was calculated. Nonparametric statistics were used. A probability value of <0.1 was considered statistically significant. RESULTS: Granulocytes from normal pregnant women had a higher median mean channel brightness for CD14 and CD64, but lower median mean channel brightness for CD16 and HLA-DR than granulocytes of nonpregnant women. Granulocytes of patients with acute infection had a higher median mean channel brightness for CD64 and CD66b than granulocytes of normal pregnant women. Monocytes from patients with acute infection had a higher mean channel brightness for CD11b, CD16, CD18, CD49d, CD64, and CD66b than monocytes of normal pregnant women. Baseline intracellular reactive oxygen species, oxidative burst, and stimulation index values were significantly higher in the granulocytes and monocytes of normal pregnant women than in the granulocytes and monocytes of nonpregnant women. Similarly, baseline intracellular reactive oxygen species, oxidative burst, and stimulation index values were higher in women with acute infections than in normal pregnant women. CONCLUSION: Normal pregnancy was associated with phenotypic and metabolic changes of granulocytes and monocytes; pregnant women with acute infection had more marked phenotypic and metabolic changes of leukocytes than normal pregnant women. These qualitative differences indicate that the innate limb of the immune response is not maximally activated during normal pregnancy. C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011 NR 21 TC 81 Z9 83 U1 0 U2 6 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2001 VL 185 IS 5 BP 1118 EP 1123 DI 10.1067/mob.2001.117682 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 496LB UT WOS:000172396100022 PM 11717644 ER PT J AU Gervasi, MT Chaiworapongsa, T Naccasha, N Blackwell, S Yoon, BH Maymon, E Romero, R AF Gervasi, MT Chaiworapongsa, T Naccasha, N Blackwell, S Yoon, BH Maymon, E Romero, R TI Phenotypic and metabolic characteristics of maternal monocytes and granulocytes in preterm labor with intact membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2001 CL RENO, NEVADA SP Soc Maternal Fetal Med DE preterm labor; leukocyte phenotype; maternal inflammatory response; inflammation; parturition ID WHOLE-BLOOD; INTRAAMNIOTIC INFECTION; PARTURITION; LEUKOCYTES; TERM AB OBJECTIVE: Experimental and clinical, studies support a role for the fetus in the control of the onset of labor. Fetal systemic Inflammation, but not a maternal inflammatory response, has been linked to the onset of preterm labor and delivery on the basis of the determination of inflammatory cytokines in fetal and maternal blood. We propose that parturition requires fetomaternal cooperation and that inflammation is an integral part of the parturitional process. This study used flow cytometry a sensitive technique for the detection of intravascular inflammation, to assess whether maternal inflammation is present in preterm labor. STUDY DESIGN: A prospective cross-sectional study was performed including patients with preterm labor (n = 55) and women with normal pregnancy (n = 50). Intravascular inflammation was studied by using flow cytometry. Maternal blood was assayed to determine granulocyte and monocyte phenotype by using monoclonal antibodies, which included the following cluster of differentiation (CD) markers: CD11b, CD14, CD15, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Oxidative burst and generation of basal intracellular oxygen radical species were assessed. Statistical analysis was conducted with the use of nonparametric methods. A P value of <0.1 was considered statistically significant. RESULTS: Preterm labor was associated with a significant increase in the median mean channel brightness of CD11b, CD15, and CD66b on granulocytes and median mean channel brightness of CD11b and CD15 on monocytes. The ratio of oxidative burst over basal intracellular oxygen radical species in both granulocytes and monocytes was increased in preterm labor (P <. 01). CONCLUSION: Preterm labor with intact membranes is associated with phenotypic and metabolic changes of maternal granulocytes and monocytes. C1 Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch,Dept OB GYN, Detroit, MI 48201 USA. Seoul Natl Univ, Seoul, South Korea. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch,Dept OB GYN, 4707 St Antoine Blvd, Detroit, MI 48201 USA. RI Yoon, Bo Hyun/H-6344-2011 NR 20 TC 51 Z9 52 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2001 VL 185 IS 5 BP 1124 EP 1129 DI 10.1067/mob.2001.117681 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 496LB UT WOS:000172396100023 PM 11717645 ER PT J AU Maymon, E Romero, R Chaiworapongsa, T Kim, JC Berman, S Gomez, R Edwin, S AF Maymon, E Romero, R Chaiworapongsa, T Kim, JC Berman, S Gomez, R Edwin, S TI Value of amniotic fluid neutrophil collagenase concentrations in preterm premature rupture of membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2001 CL RENO, NEVADA SP Soc Maternal Fetal Med DE preterm premature rupture of membranes; neonatal morbidity; intra-amniotic infection; amniotic fluid; matrix metalloproteinases; MMP-8 ID BLOOD-CELL COUNT; MATRIX METALLOPROTEINASE-9; INTRAAMNIOTIC INFECTION; INTRAUTERINE INFECTION; INTACT MEMBRANES; PROGNOSTIC VALUE; GRAM STAIN; INTERLEUKIN-6; PARTURITION; LABOR AB OBJECTIVE: Neutrophils in amniotic fluid are thought to be of fetal origin, and therefore the detection of these cells and/or their products in amniotic fluid may reflect the fetal inflammatory status. We propose that amniotic fluid neutrophil collagenase (matrix metalloproteinase-8) is a useful parameter to predict adverse neonatal outcome, Impending preterm labor/delivery, and intrauterine Infection in the setting of preterm premature rupture of the membranes. STUDY DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis from 101 patients with preterm premature rupture of the membranes (gestational age, 24-36 weeks). Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Amniotic fluid analysis included Gram stain, white blood cell count, and determination of interleukin-6 and matrix metalloproteinase-8 concentrations (enzyme-linked immunosorbent assay). RESULTS. Neonates with adverse neonatal outcome were born to mothers with a significantly higher median amniotic fluid matrix metalloproteinase-8 concentration than those without adverse neonatal outcome (median, 54.4 ng/mL; range, 0.82-14,500 ng/mL vs median, 28.9 ng/mL; range, 0.78-2451.8 ng/mL; P < .05, respectively). The higher the amniotic fluid matrix metalloproteinase-8 concentrations, the shorter the interval to delivery (Cox proportional hazards model adjusting for gestational age at delivery; hazard ratio, 1.9; 950% Cl, 1.1-3.5; P < .03). Amniotic fluid matrix metalloproteinase-8 concentration was more sensitive than an amniotic fluid white blood cell count and interleukin-6 In the detection of microbiologically proven intra-amniotic Infection. CONCLUSION. Increased concentrations of neutrophil collagenase (matrix metalloproteinase-8) in amniotic fluid are associated with intra-amniotic infection, Impending preterm delivery, and adverse neonatal outcome in patients with preterm premature rupture of the membranes. Moreover, matrix metalloproteinase-8 in amniotic fluid is a stronger predictor for the duration of pregnancy and intra-amniotic inflammation than interleukin-6 and an amniotic fluid white blood cell count. C1 Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch, Detroit, MI 48201 USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, NICHD, Perinatol Res Branch, 4707 St Antoine Blvd, Detroit, MI 48201 USA. NR 23 TC 43 Z9 45 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2001 VL 185 IS 5 BP 1143 EP 1148 DI 10.1067/mob.2001.118166 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 496LB UT WOS:000172396100026 PM 11717648 ER PT J AU Maymon, E Romero, R Chaiworapongsa, T Berman, S Conoscenti, G Gomez, R Edwin, S AF Maymon, E Romero, R Chaiworapongsa, T Berman, S Conoscenti, G Gomez, R Edwin, S TI Amniotic fluid matrix metalloproteinase-8 in preterm labor with intact membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-Maternal-Fetal-Medicine CY FEB 05-10, 2001 CL RENO, NEVADA SP Soc Maternal Fetal Med DE matrix metalloproteinase; intra-amniotic infection; preterm labor; neonatal death; neonatal morbidity; MMP-8 ID HUMAN NEUTROPHIL COLLAGENASE; PREMATURE RUPTURE; HISTOLOGIC CHORIOAMNIONITIS; INTRAAMNIOTIC INFECTION; INTRAUTERINE INFECTION; INFLAMMATORY RESPONSE; PARTURITION; DELIVERY; INTERLEUKIN-6; AMNIOCENTESIS AB OBJECTIVE: Intra-amniotic inflammation Is a major determinant of maternal and neonatal outcome in patients with preterm labor. Matrix metalloproteinase-8 is a sensitive marker of inflammation in body fluids. This study was conducted to examine the value of amniotic fluid matrix metalloproteinase-8 determinations In patients with preterm, labor and Intact membranes, STUDY DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis from 371 patients with preterm labor. Fluid was cultured for aerobic and anaerobic bacteria and Mycoplasmas. Amniotic fluid analysis included Gram stain examination, white blood cell count, and matrix metalloproteinase-8 (enzyme-linked immunosorbent assay) determination. Nonparametric statistics were used for analysis. RESULTS: The rate of preterm delivery was 54% (200/371) and that of intra-amniotic infection was 9.2% (34/371). The median amniotic fluid matrix metalloproteinase-8 concentration was more than 50-fold higher In patients with Intra-amniotic infection than in patients with no intra-amniotic Infection (median, 605.6 ng/mL; range, 0.65-15,000 ng/mL vs median, 10.6 ng/mL; range, <0.06-16,600 ng/mL, respectively P < .0001). The matrix metalloproteinase-8 amniotic fluid concentrations were significantly higher in patients who delivered preterm than in patients who delivered at term (median, 19.5 ng/mL; range, <0.06-16,600 ng/mL vs median, 2.1 ng/mL; range, <0.06-500 ng/mL, respectively; P < .001). After exclusion of patients with intra-amniotic Infection, patients who delivered preterm had a significantly higher median amniotic fluid matrix metalloproteinase-8 than patients who delivered at term (P < .05). An amniotic fluid matrix metalloproteinase-8 level of > 30 ng/mL was an independent predictor for the occurrence of neonatal morbidity (odds ratio, 3.4; 95% Cl, 1.9-5.8; P < .01). CONCLUSION: Increased amniotic fluid matrix metalloproteinase-8 concentrations identify patients at risk for intra-amniotic infection, Impending preterm delivery, and adverse neonatal outcome. C1 NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, Perinatol Res Branch, NICHD,Dept Obstet & Gynecol, 4707 St Antoine Blvd, Detroit, MI 48201 USA. NR 23 TC 49 Z9 51 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2001 VL 185 IS 5 BP 1149 EP 1155 DI 10.1067/mob.2001.118165 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 496LB UT WOS:000172396100027 PM 11717649 ER PT J AU Gray, RH Wabwire-Mangen, F Kigozi, G Sewankambo, NK Serwadda, D Moulton, LH Quinn, TC O'Brien, KL Meehan, M Abramowsky, C Robb, M Wawer, MJ AF Gray, RH Wabwire-Mangen, F Kigozi, G Sewankambo, NK Serwadda, D Moulton, LH Quinn, TC O'Brien, KL Meehan, M Abramowsky, C Robb, M Wawer, MJ TI Randomized trial of presumptive sexually transmitted disease therapy during pregnancy in Rakai, Uganda SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE sexually transmitted disease; HIV; birth weight; preterm; neonatal death; perinatal HIV transmission ID GENITAL-TRACT INFECTIONS; BACTERIAL VAGINOSIS; RURAL TANZANIA; PRETERM DELIVERY; COMMUNITY TRIAL; HIV-INFECTION; TRANSMISSION; PREVENTION; METRONIDAZOLE; NEWBORN AB OBJECTIVE: The purpose of this study was to assess presumptive sexually transmitted disease treatment on pregnancy outcome and HIV transmission. STUDY DESIGN: In a randomized trial in Rakai District, Uganda, 2070 pregnant women received presumptive sexually transmitted disease treatment 1 time during pregnancy at varying gestations, and 1963 control mothers received iron/folate and referral for syphilis. Maternal-infant sexually transmitted disease/HIV and infant outcomes were assessed. Intent-to-treat analyses estimated adjusted rate ratios and 95% confidence intervals. RESULTS: Sexually transmitted diseases were reduced: Trichomonas vaginalis (rate ratio, 0.28; 95% Cl, 0.18%-0.49%), bacterial vaginosis (rate ratio, 0.78; 95% Cl, 0.69-0.87), Neisseria gonorrhoeae/Chlamydia trachomatis (rate ratio, 0.43; 95% Cl, 0.27-0.68), and infant ophthalmia (rate ratio, 0.37; 95% Cl, 0.20-0.70). There were reduced rates of neonatal death (rate ratio, 0.83; 95% Cl, 0.71-0.97), low birth weight (rate ratio, 0.68; 95% Cl, 0.53-0.86), and preterm delivery (rate ratio, 0.77; 95% Cl, 0.56-1.05); but there were no effects on maternal HIV acquisition or perinatal HIV transmission. CONCLUSION: Reductions of maternal sexually transmitted disease improved pregnancy outcome but not maternal HIV acquisition or perinatal HIV transmission. C1 Johns Hopkins Univ, Dept Populat & Family Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Uganda Virus Res Inst, Rakai Project, Entebbe, Uganda. Makerere Univ, Dept Med, Kampala, Uganda. Makerere Univ, Clin Epidemiol Unit, Kampala, Uganda. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, NIH, Rockville, MD 20852 USA. Columbia Univ, Ctr Populat & Family Hlth, Joseph L Mailman Sch Publ Hlth, New York, NY 10027 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Pathol, Washington, DC 20307 USA. RP Gray, RH (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Suite 4030,615 N Wolfe St, Baltimore, MD 21205 USA. OI Sewankambo, Nelson/0000-0001-9362-053X; Moulton, Lawrence/0000-0001-7041-7387 FU FIC NIH HHS [5D43TW00010]; NIAID NIH HHS [R01 AI3426S, R01 AI34826]; NICHD NIH HHS [5P30HD06826] NR 25 TC 85 Z9 86 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2001 VL 185 IS 5 BP 1209 EP 1217 DI 10.1067/mob.2001.118158 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 496LB UT WOS:000172396100037 PM 11717659 ER PT J AU Djalilian, AR Smith, JA Walsh, TJ Malech, HL Robinson, MR AF Djalilian, AR Smith, JA Walsh, TJ Malech, HL Robinson, MR TI Keratitis caused by Candida glabrata in a patient with chronic granulomatous disease SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ENDOPHTHALMITIS AB PURPOSE: To report an unusual ocular presentation of Candida glabrata in a patient with chronic granulomatous disease. METHODS: Interventional case report. A 15-year-old boy with chronic granulomatous disease presented with bilateral limbal infiltrates. He had been receiving broad-spectrum systemic antibiotics for recurrent liver abscesses. The keratitis did not respond to antibiotics and did not resolve after a course of topical steroids. RESULTS: Corneal cultures revealed Candida glabrata. The same species was simultaneously isolated from the surgical drainage of the liver abscesses. The ocular and hepatic findings resolved on intravenous amphotericin B. CONCLUSION: Candida glabrata has recently emerged as an important nosocomial pathogen. It may present as a limbal keratitis in the setting of systemic infection. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 NEI, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Djalilian, AR (reprint author), NEI, NIH, Bldg 10,Rm 10N202,10 Ctr Dr MSC 1863, Bethesda, MD 20892 USA. NR 6 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2001 VL 132 IS 5 BP 782 EP 783 DI 10.1016/S0002-9394(01)01091-1 PG 2 WC Ophthalmology SC Ophthalmology GA 487PP UT WOS:000171884700023 PM 11704043 ER PT J AU Fine, HF Baffi, J Reed, GF Csaky, KG Nussenblatt, RB AF Fine, HF Baffi, J Reed, GF Csaky, KG Nussenblatt, RB TI Aqueous humor and plasma vascular endothelial growth factor in uveitis-associated cystoid macular edema SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To determine the association between cystoid macular edema and vascular endothelial growth factor concentration in the aqueous humor and plasma of uveitis patients. METHODS: Cross-sectional study. Vascular endothelial growth factor concentrations were measured by enzyme-linked immunosorbent assay in the aqueous humor of 20 uveitis patients (9 with and 11 without cystoid macular edema), and in the plasma of 40 uveitis patients (20 with and 20 without cystoid macular edema) and 20 healthy volunteers. RESULTS: Mean aqueous humor vascular endothelial growth factor concentrations for uveitis patients with and without cystoid macular edema were 152.3 and 109.5 pg/ml, respectively, P = .044. Mean plasma vascular endothelial growth factor concentrations in uveitis patients with and without cystoid macular edema and in healthy volunteers were 32.2, 29.6, and 55.0 pg/ml, respectively. Uveitis patients had lower plasma vascular endothelial growth factor levels than did healthy volunteers, P = .0002 CONCLUSION: In uveitis patients, vascular endothelial growth factor concentration is increased in the aqueous humor of eyes with cystoid macular edema. It may be useful to investigate vascular endothelial growth factor antagonists as a treatment for uveitis-associated cystoid macular edema. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 NEI, NIH, Immunol Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. NEI, Biometry Branch, NIH, Bethesda, MD 20892 USA. RP Fine, HF (reprint author), NEI, NIH, Immunol Lab, 10-10N202,10 Ctr Dr,MSC 1863, Bethesda, MD 20892 USA. NR 5 TC 63 Z9 65 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2001 VL 132 IS 5 BP 794 EP 796 DI 10.1016/S0002-9394(01)01103-5 PG 3 WC Ophthalmology SC Ophthalmology GA 487PP UT WOS:000171884700030 PM 11704050 ER PT J AU Morrisey, K Evans, RA Wakefield, L Phillips, AO AF Morrisey, K Evans, RA Wakefield, L Phillips, AO TI Translational regulation of renal proximal tubular epithelial cell transforming growth factor-beta 1 generation by insulin SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-BETA-1 MESSENGER-RNA; DIABETIC NEPHROPATHY; TGF-BETA-1 SYNTHESIS; GENE-TRANSCRIPTION; FACTOR-BETA; EXPRESSION; ACTIVATION; PATHWAYS; 3-KINASE; KIDNEY AB We have previously demonstrated that the proximal tubular cell may contribute to the pathogenesis of renal interstitial fibrosis in diabetes. Transforming growth factor (TGF)-beta1 is one of a group of pro-fibrotic cytokines and growth factors, which have been associated with the development of interstitial fibrosis. The aim of the current study was to examine the effect of insulin on the generation of TGF-beta1. by proximal tubular cells. HK-2 cells were grown to confluence in the absence of insulin, and serum deprived for 48 hours before all experimental manipulations. Addition of insulin (5 mug/ml) to the culture medium led to a time-dependent increase in TGF-beta1 concentration in the cell culture supernatant, and increased incorporation of radiolabeled amino acids into TGF-beta1 suggestive of de novo TGF-beta1 protein synthesis. Addition of insulin did not alter TGF-beta1 mRNA expression as assessed by reverse transcriptase-polymerase chain reaction or Northern analysis. insulin-induced increase in TGF-beta1 concentration was not abrogated by actinomycin D, however, stimulation by insulin, in the presence of cycloheximide led to a dose-dependent decrease in TGF-beta1 production. Addition of insulin had no effect on TGF-beta1 mRNA stability as assessed by actinomycin D chase, but led to increased binding of a cytoplasmic protein to a putative stem loop structure in the 5'-UTR of TGF-beta1 mRNA, previously implicated in the posttranscriptional control of TGF-beta1 synthesis. To address the functional significance of insulin-induced alteration in TGF-beta1 synthesis, we examined its effect on matrix turnover. Insulin stimulated type IV collagen gene expression and an increase in the concentrations of the type IV collagen laid down in the extracellular matrix. This increase in type IV collagen was abrogated when cells were stimulated by insulin in the presence of an anti-TGF-beta1-blocking antibody. in conclusion the data demonstrate that insulin may directly alter the production of TGF-beta1 by renal proximal tubular cells by a posttranscriptional mechanism, and that this may have implications for the increase in extracellular matrix that accompanies diabetic nephropathy. C1 Univ Wales Coll Med, Inst Nephrol, Cardiff CF14 4XN, S Glam, Wales. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Phillips, AO (reprint author), Univ Wales Coll Med, Inst Nephrol, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. NR 36 TC 47 Z9 60 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2001 VL 159 IS 5 BP 1905 EP 1915 DI 10.1016/S0002-9440(10)63037-4 PG 11 WC Pathology SC Pathology GA 489JJ UT WOS:000171988000033 PM 11696451 ER PT J AU Meyer-Lindenberg, A Poline, JB Kohn, PD Holt, JL Egan, MF Weinberger, DR Berman, KF AF Meyer-Lindenberg, A Poline, JB Kohn, PD Holt, JL Egan, MF Weinberger, DR Berman, KF TI Evidence for abnormal cortical functional connectivity during working memory in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PRINCIPAL-COMPONENT ANALYSIS; FMRI DATA; DYSFUNCTION; PET; NEUROPATHOLOGY; NETWORK; CORTEX; BRAIN AB Objective: Disturbed neuronal interactions may be involved in schizophrenia because it is without clear regional pathology. Aberrant connectivity is further suggested by theoretical formulations and neurochemical and neuroanatomical data. The authors applied to schizophrenia a recently available functional neuroimaging analytic method that permits characterization of cooperative action on the systems level. Method: Thirteen medication-free patients and 13 matched healthy comparison subjects performed a working memory (n-back) task and sensorimotor baseline task during positron emission tomography. "Functional connectivity" patterns, reflecting distributed correlated activity that differed most between groups, were extracted by a canonical variates analysis. Results: More than half the variance was explained by a single pattern showing inferotemporal, (para-)hippocampal, and cerebellar loadings for patients versus dorsolateral prefrontal and anterior cingulate activity for comparison subjects. Expression of this pattern perfectly separated all patient scans from comparison scans, thus showing promise as a trait marker. This result was validated prospectively by successfully classifying unrelated scans from the same patients and data from a new cohort. An additional 19% of variance corresponded to the pattern activated by the working memory task. Expression of this pattern was more variable in patients during working memory but not the control condition, suggesting inability to sustain a task-adequate neural network, consistent with the disconnection hypothesis. Conclusions: Pronounced disruptions of distributed cooperative activity in schizophrenia were found. A pattern showing disturbed frontotemporal interactions showed promise as a trait marker and may be useful for future investigations. C1 NIH, Unit Integrat Neuroimaging, Intramural Res Program, Bethesda, MD 20892 USA. CEA, Serv Hosp Frederic Joliot, Dept Rech Med, F-91406 Orsay, France. RP Meyer-Lindenberg, A (reprint author), NIH, Unit Integrat Neuroimaging, Intramural Res Program, Bldg 10,Room 4C101,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 32 TC 330 Z9 335 U1 6 U2 26 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2001 VL 158 IS 11 BP 1809 EP 1817 DI 10.1176/appi.ajp.158.11.1809 PG 9 WC Psychiatry SC Psychiatry GA 488QC UT WOS:000171946300007 PM 11691686 ER PT J AU Egan, MF Hyde, TM Bonomo, JB Mattay, VS Bigelow, LB Goldberg, TE Weinberger, DR AF Egan, MF Hyde, TM Bonomo, JB Mattay, VS Bigelow, LB Goldberg, TE Weinberger, DR TI Relative risk of neurological signs in siblings of patients with schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GENETICALLY COMPLEX TRAITS; SOFT SIGNS; EVOLUTIONARY ORIGINS; TARDIVE-DYSKINESIA; LINKAGE STRATEGIES; ABNORMALITIES; HANDEDNESS; POPULATION; PSYCHOSIS; DEFICITS AB Objective: First-degree relatives of patients with schizophrenia appear to have subtle neurological signs, suggesting that these measures could serve as intermediate phenotypes in genetic studies of schizophrenia. The strength of a possible genetic component is unknown, however, leaving it uncertain whether such traits could increase the power to find schizophrenia susceptibility loci. The authors' goal was to investigate the strength of this possible genetic component. Method: They estimated the relative risk of neurological impairments in a large group of siblings of patients with schizophrenia. Two standard neurological scales (the Neurological Evaluation Scale and the Woods Scale) were used to examine 115 patients, 185 of their siblings, and 88 normal comparison subjects. Results: There were significant differences between the siblings of patients with schizophrenia and the normal comparison subjects only on the Woods Scale. Relative risk of neurological impairment was significantly increased in the sibling group, but the significance was weak to moderate. Neurological impairment was not redundant with several other intermediate phenotypic measures based on cognitive impairment. Conclusions: These data suggest that neurological signs cluster in patients with schizophrenia and their families and could possibly identify a unique component of genetic variance for risk of schizophrenia. However, the fairly low relative risk and the uncertain pathophysiology of such signs may limit their usefulness. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Egan, MF (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bldg 10,Ctr Dr,Rm 4S-241,MSC1395, Bethesda, MD 20892 USA. NR 50 TC 74 Z9 75 U1 4 U2 9 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2001 VL 158 IS 11 BP 1827 EP 1834 DI 10.1176/appi.ajp.158.11.1827 PG 8 WC Psychiatry SC Psychiatry GA 488QC UT WOS:000171946300009 PM 11691688 ER PT J AU Fee, E Brown, TM Lazarus, J Theerman, P AF Fee, E Brown, TM Lazarus, J Theerman, P TI Immigrant mother and child: Chicago, 1910 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2001 VL 91 IS 11 BP 1764 EP 1764 DI 10.2105/AJPH.91.11.1764 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 487CE UT WOS:000171855400015 PM 11684596 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI Alice Hamilton: Settlement physician, occupational health pioneer SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 3 Z9 4 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2001 VL 91 IS 11 BP 1767 EP 1767 DI 10.2105/AJPH.91.11.1767 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 487CE UT WOS:000171855400017 PM 11684598 ER PT J AU Harik-Khan, RI Fleg, JL Muller, DC Wise, RA AF Harik-Khan, RI Fleg, JL Muller, DC Wise, RA TI The effect of anthropometric and socioeconomic factors on the racial difference in lung function SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE respiratory function tests; anthropology, physical; social class; body mass index; reference values ID SPIROMETRIC REFERENCE VALUES; PULMONARY-FUNCTION; VENTILATORY FUNCTIONS; MEXICAN-AMERICAN; NORMAL-CHILDREN; WHITE-CHILDREN; YOUNG-ADULTS; RISK-FACTORS; WEIGHT-GAIN; BLACK AB African-Americans have lower lung function than whites. However, the relative contributions of body habitus and socioeconomic factors are unknown. To address this question, we analyzed data from 1242 white (806 women, 436 men) and 1084 African-American (696 women, 388 men) asymptomatic, nonsmoking adult participants of the third National Health and Nutrition Examination Survey (NHANES III). African-Americans were poorer, had larger FEV1/FVC and body mass index (BMI), but lower sitting height, FEV1 and FVC than whites. Cross-sectional regression analyses using spirometric, anthropometric, and socioeconomic data were performed separately by sex to investigate racial differences in lung function. Sitting height accounted for 35-39% of the race difference in both sexes. Poverty index accounted for about 7.5% and 2.5% of the racial difference in women and men, respectively, whereas the effect of education accounted for about 2% in women and 4.7% in men. With further adjustment for BMI, we could account for only about half of the racial difference in FEV1 and FVC. We conclude that the racial difference in lung function is only partially explained by a shorter upper body segment in African-Americans. Although low socioeconomic indicators are related to lower lung function, they explain only a small proportion of this racial difference. C1 NIA, Clin Res Branch, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. Johns Hopkins Asthma & Allergy Ctr, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. RP Harik-Khan, RI (reprint author), NIA, Clin Res Branch, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr,Box 06, Baltimore, MD 21224 USA. NR 30 TC 58 Z9 60 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2001 VL 164 IS 9 BP 1647 EP 1654 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 499RR UT WOS:000172584600016 PM 11719304 ER PT J AU Gottlieb, DJ Wilk, JB Harmon, M Evans, JC Joost, O Levy, D O'Connor, GT Myers, RH AF Gottlieb, DJ Wilk, JB Harmon, M Evans, JC Joost, O Levy, D O'Connor, GT Myers, RH TI Heritability of longitudinal change in lung function - The Framingham Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE spirometry; epidemiologic studies; genetics ID OBSTRUCTIVE PULMONARY-DISEASE; SEGREGATION ANALYSIS; FAMILY; EPIDEMIOLOGY; SMOKING; SAMPLE; TWINS; RISK AB There have been multiple reports of heritability of lung function in cross-sectional analysis, but no prior reports of heritability of rate of change in lung function. We examined heritability of rate of change of lung function in families participating in the Framingham Heart Study. Spirometric measures from two time points were used to calculate annualized rate of change in FEV1, FVC, and FEV1/FVC ratio, adjusting for the effects of age, height, and weight using multiple linear regression models. Standardized residuals from these models were used as phenotypic variables in variance components analysis to assess effects of smoking and heritable factors on rate of change in lung function. Heritable factors explained a modest proportion of the population variance, with heritability estimates for change in FEV1, FVC, and ratio of 0.05, 0.18, and 0.13, respectively. Restricting the analysis to subjects concordant for smoking status during the interval over which lung function was measured, the heritability estimates increased to 0.18, 0.39, and 0.14, respectively, among interim smokers. These data suggest that in middle-aged and older persons in the general population, genetic factors contribute modestly to the overall population variance in rate of lung function decline, and further suggest the importance of gene-environment interactions. C1 VA Boston Healthcare Syst, Res Serv, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Gottlieb, DJ (reprint author), Ctr Pulm, 715 Albany St,R-304, Boston, MA 02118 USA. OI O'Connor, George/0000-0002-6476-3926 FU NHLBI NIH HHS [HL-49869, N01-HC-38038] NR 23 TC 38 Z9 38 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2001 VL 164 IS 9 BP 1655 EP 1659 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 499RR UT WOS:000172584600017 PM 11719305 ER PT J AU Seto, B AF Seto, B TI History of medical ethics and perspectives on disparities in minority recruitment and involvement in health research SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT National Conference on Capicity Building for Reasearch in Minority Health CY MAY 03-05, 2000 CL JACKSON, MISSISSIPPI DE medical ethics; history; abuse; minority recruitment AB The legitimate and successful recruitment of minorities as research participants in clinical trials should be addressed from an ethical and historical perspective. To gain an appreciation of the challenges, to develop strategies and to overcome the disparities of minority involvement in clinic trials, it is essential to be cognizant of previous violations and abuses of ethics and human rights. Also significant are major legislation, regulations and federal initiatives that resulted from those abuses. From history, we have learned we cannot generalize data and assume that, if we have the majority group in clinical trials, then we can accurately apply that data to minorities. There are cultural and environmental differences; thus, it is absolutely crucial that researchers approach recruitment of minority groups with cultural competence and cultural sensitivity. Federal regulations and legislation set the framework for protection of human participants in research. C1 NIH, Off Reports & Anal, Off Extramural Res, Bethesda, MD 20892 USA. RP Seto, B (reprint author), NIH, Off Reports & Anal, Off Extramural Res, 1 Ctr Dr,MSC 0164,Room 252, Bethesda, MD 20892 USA. NR 26 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD NOV PY 2001 VL 322 IS 5 BP 246 EP 250 DI 10.1097/00000441-200111000-00002 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 492QE UT WOS:000172178400002 ER PT J AU Ruffin, J Flagg-Newton, JL AF Ruffin, J Flagg-Newton, JL TI Building capacity for health disparity research at minority institutions SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT National Conference on Capicity Building for Reasearch in Minority Health CY MAY 03-05, 2000 CL JACKSON, MISSISSIPPI DE minority health; research; funding; NIH; EPSCOR AB The science and technology enterprise of the United States has consistently produced seminal work and cutting-edge technologies. It has responded promptly to both new opportunities and urgent crises. The success of this enterprise derives largely from the diversity of the types of institutions doing the work and from the many sources of public and private funding available to accomplish it. To those who argue that public-sector funds should support only the best science at the premier research institutions on the nation's East and West coasts, Dr. Rita Colwell, the director of the National Science Foundation (NSF) eloquently responds, "No one region, no one group of institutions, and no special communities have a corner on the market of good and great ideas, smart people, or outstanding researchers. Great ideas can come from just about anywhere.". C1 NIH, Minor Hlth Initiat Off Res, Bethesda, MD 20892 USA. RP Flagg-Newton, JL (reprint author), NIH, Minor Hlth Initiat Off Res, 1 Ctr Dr,MSC 0164,Room 260, Bethesda, MD 20892 USA. NR 24 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD NOV PY 2001 VL 322 IS 5 BP 251 EP 256 DI 10.1097/00000441-200111000-00003 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 492QE UT WOS:000172178400003 PM 11721796 ER PT J AU Durbin, AP Karron, RA Sun, W Vaughn, DW Reynolds, MJ Perreault, JR Thumar, B Men, R Lai, CJ Elkins, WR Chanock, RM Murphy, BR Whitehead, SS AF Durbin, AP Karron, RA Sun, W Vaughn, DW Reynolds, MJ Perreault, JR Thumar, B Men, R Lai, CJ Elkins, WR Chanock, RM Murphy, BR Whitehead, SS TI Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3 '-untranslated region SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID YELLOW-FEVER; NONHUMAN-PRIMATES; VOLUNTEERS; CONSTRUCTION; GENES; IMMUNIZATION; RECOMBINANT; RESPONSES; SEQUENCE; PROTEIN AB The recombinant dengue virus type-4 vaccine candidate 2A Delta 30 was attenuated in rhesus monkeys due to an engineered 30-nucleotide deletion in the 3'-untranslated region of the viral genome. A clinical trial to evaluate the safety and immunogenicity of a single dose of 2A Delta 30 was conducted with 20 adult human volunteers. The vaccine candidate was well tolerated and did not cause systemic illness in any of the 20 volunteers. Viremia was detectable in 14 volunteers at a mean level of 1.6 log(10) plaque-forming units/ml of serum, although all 20 volunteers seroconverted with a seven-fold or greater increase in serum neutralizing antibody titer on day 28 post-vaccination (mean titer = 1:580). A mild, asymptomatic, macular rash developed in 10 volunteers, and a transient elevation in the serum level of alanine aminotransferase was noted in five volunteers. The low level of reactogenicity and high degree of immunogenicity of this vaccine candidate warrant its further evaluation and its use to create chimeric vaccine viruses expressing the structural genes of dengue virus types 1, 2, and 3. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD 21205 USA. Walter Reed Army Inst Res, Dept Virus Dis, Silver Spring, MD 20910 USA. RP Whitehead, SS (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Room 100,7 Ctr Dr, Bethesda, MD 20892 USA. NR 43 TC 168 Z9 179 U1 0 U2 5 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2001 VL 65 IS 5 BP 405 EP 413 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 491ZD UT WOS:000172139700004 PM 11716091 ER PT J AU Troyer, JM Hanley, KA Whitehead, SS Strickman, D Karron, RA Durbin, AP Murphy, BR AF Troyer, JM Hanley, KA Whitehead, SS Strickman, D Karron, RA Durbin, AP Murphy, BR TI A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID AEDES-AEGYPTI; ORAL INFECTION; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; CONSTRUCTION; SUSCEPTIBILITY; VIREMIA; IMPACT; TYPE-4; GENES AB 2A Delta 30 is a live dengue-4 virus vaccine candidate with a 30-nucleotide deletion in its 3'-untranslated region. To assess the transmissibility of 2A Delta 30 by mosquitoes, we compared its in vivo replication in mosquitoes with that of its wild type DEN-4 parent. Both the vaccine candidate and wild type virus were equally able to infect the mosquito Toxorhynchites splendens after intrathoracic inoculation. Relative to its wild type parent, 2A Delta 30 was slightly restricted in its ability to infect the midgut of Aedes aegypti mosquitoes fed on an artificial blood meal and was even more restricted in its ability to disseminate from the midgut to the salivary glands. Thus, the 30-nucleotide deletion rendered the vaccine candidate more sensitive than its wild type parent to the mosquito rnidgut escape barrier. Most significantly, 2A Delta 30 was not transmitted to 352 Ae. albopictus mosquitoes fed on 10 vaccinees. all of whom were infected with the vaccine candidate. C1 Walter Reed Army Inst Res, Dept Entomol, Silver Spring, MD 20910 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. RP Troyer, JM (reprint author), Walter Reed Army Inst Res, Dept Entomol, 503 Robert Grant Rd, Silver Spring, MD 20910 USA. NR 34 TC 72 Z9 74 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2001 VL 65 IS 5 BP 414 EP 419 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 491ZD UT WOS:000172139700005 PM 11716092 ER PT J AU Steel, C Ottesen, EA Weller, PF Nutman, TB AF Steel, C Ottesen, EA Weller, PF Nutman, TB TI Worm burden and host responsiveness in Wuchereria bancrofti infection: Use of antigen detection to refine earlier assessments from the South Pacific SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ONCHOCERCIASIS-CONTROL-PROGRAMME; CIRCULATING PARASITE ANTIGEN; BRUGIA-PAHANGI; LYMPHATIC FILARIASIS; MICROFILARIAL LOAD; SEX; DIETHYLCARBAMAZINE; SUSCEPTIBILITY; IMMUNITY; AREA AB A population from the Witchereria bancrofti-endemic island of Mauke was reevaluated retrospectively by use of the Og4C3 circulating antigen (CAg) enzyme-link-ed immunosorbent assay to assess active infection in relation to host responses by age and gender. Use of microfilaremia (Mf) alone misclassified similar to 50% of infected people, although CAg and Mf levels were positively correlated. Levels of CAg peaked between those aged 31-60 years; men aged > 60 years had a significantly higher CAg prevalence (> 90%) than women. Filaria-specific immunoglobulin (Ig) G4 reached maximum levels in both genders at age 51-60 years. By analysis of variance, both age and gender significantly influenced CAg and IgG4, with men having higher levels of both in the total Population. Individuals positive for CAg had significantly lower lymphocyte proliferation responses to parasite antigen than did CAg-negative people, regardless of clinical status. This study reemphasizes the importance of CAg measurements for accurately assessing filarial prevalence and clinical status and demonstrates the relationship between active infection and immune responsiveness. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. WHO, Dept Control Prevent & Eradicat Infect Dis, CH-1211 Geneva, Switzerland. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Steel, C (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. NR 49 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2001 VL 65 IS 5 BP 498 EP 503 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 491ZD UT WOS:000172139700017 PM 11716104 ER PT J AU Neva, FA Gam, AA Maxwell, C Pelletier, LL AF Neva, FA Gam, AA Maxwell, C Pelletier, LL TI Skin test antigens for immediate hypersensitivity prepared from infective larvae of Strongyloides stercoralis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID EX-PRISONERS; WAR AB More rapid and simplified diagnostic procedures are needed for the diagnosis of strongyloidiasis. One approach is the use of an immediate hypersensitivity skin test that would reliably identify infected people. Accordingly, somatic and excretion/secretion (E/S) antigens were prepared from filariform larvae of Strongyloides stercoralis and were treated to remove possible adventitious agents. By use of a quantitative method for measurement of skin reactions, several preparations of the 2 antigens were tested in uninfected controls and in various groups of patients. Doses of 0.35 mug of E/S and 4 mug of somatic antigens elicited positive skin tests in 82-100% of infected people, depending on clinical status. A lower frequency of positive skin tests was found in strongyloidiasis patients also infected with human T-cell lymphotropic virus type 1. Cross-reactions, especially to somatic antigens, were frequently found in patients with filarial infections. Despite these limitations and the need for further study of specificity, these results provide a basis for future development of a diagnostic skin test antigen for strongyloidiasis. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Vet Adm Primary Care Facil, Med Serv, Wichita, KS 67218 USA. RP Neva, FA (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Bldg 40413, Bethesda, MD 20892 USA. NR 15 TC 12 Z9 13 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2001 VL 65 IS 5 BP 567 EP 572 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 491ZD UT WOS:000172139700029 PM 11716116 ER PT J AU Porto, AF Oliveira, J Neva, FA Orge, G Alcantara, L Gam, A Carvalho, EM AF Porto, AF Oliveira, J Neva, FA Orge, G Alcantara, L Gam, A Carvalho, EM TI Influence of human T-cell lymphocytotropic virus type 1 infection on serologic and skin tests for strongyloidiasis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID I INFECTION; STERCORALIS; RESPONSES; LEUKEMIA; OKINAWA; JAPAN AB The aim of this study was to determine whether human T-cell lymphocytotropic virus type I (HTLV-1) infection may affect the levels of parasite-specific immunoglobulin (Ig) G and IgE and the positivity of the skin test for strongyloidiasis. Participants included 67 patients with strongyloidiasis (40 without HTLV-1 infection and 27 coinfected with HTLV-1). We determined IgG and IgE levels by enzyme-linked immunosorbent assay, and the immediate hypersensitivity skin test was performed with the metabolic Strongyloides stercoralis antigen. Specific I-E levels and the size of skin reactions in patients without HTLV-1 were higher (P < 0.01) than those observed in patients coinfected with HTLV-1. Additionally, 89% of patients without HTLV-1 had specific IgE and 92.5% had positive skin tests; however, these values were significantly reduced (P < 0.01) in patients coinfected with HTLV-1 (44%, and 59%, respectively). These data show that HTLV-1 infection decreases the sensitivity of detection of S. stercoralis-specific IgE, the size of the immediate hypersensitivity reaction, and the sensitivity of these tests in the diagnosis of strongyloidiasis. C1 Univ Fed Bahia, Hosp Univ Prof Edgard Santos, Serv Imunol, Lab Imunol, BR-40110160 Salvador, BA, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Carvalho, EM (reprint author), Univ Fed Bahia, Hosp Univ Prof Edgard Santos, Serv Imunol, Lab Imunol, 5 Andar,Rua Joao das Botas S-N Canela, BR-40110160 Salvador, BA, Brazil. FU NIAID NIH HHS [AI-30639] NR 20 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2001 VL 65 IS 5 BP 610 EP 613 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 491ZD UT WOS:000172139700036 PM 11716123 ER PT J AU Soltis, J McElreath, R AF Soltis, J McElreath, R TI Can females gain extra paternal investment by mating with multiple males? A game theoretic approach SO AMERICAN NATURALIST LA English DT Article DE female multiple mating; polyandry; nonprocreative mating; paternal investment; mating benefits; mating strategy ID MACAQUES MACACA-SYLVANUS; MALE PARENTAL CARE; PRUNELLA-MODULARIS; BARBARY MACAQUES; MATE CHOICE; REPRODUCTIVE STRATEGIES; GENETIC INCOMPATIBILITY; SAGUINUS-FUSCICOLLIS; COURTSHIP STRATEGY; JAPANESE MACAQUES AB Although females may require only one mating to become inseminated, many female animals engage in costly mating with multiple males. One potential benefit of polyandrous mating is gaining parental investment from multiple males. We developed two game theoretic models to explore this possibility. Our first model showed that male care of multiple females' offspring evolves when male help substantially increases offspring fitness, future mating opportunity is limited, and group size is small. In our second model, we assumed that males invest in the offspring of former mates and evaluated the fitness consequences of female monogamous and polyandrous mating strategies. Females benefit only from limited polyandry, that is, mating with several males. Polyandry is discouraged because females must share male investment with other polyandrous females, and paternal care is likely to experience diminishing returns. Females may enhance their access to male investment by competing with rival females and monopolizing investment, however. The results support the argument that females can gain paternal investment by mating with several males in small social groups (e.g., dunnocks Prunella modularis). The results do not support the argument that females can gain paternal investment from pronounced multiple mating in large social groups, however, as observed in many primate species. C1 NIH, Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA. RP Soltis, J (reprint author), NIH, Anim Ctr, Comparat Ethol Lab, Box 529, Poolesville, MD 20837 USA. NR 68 TC 19 Z9 19 U1 3 U2 15 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0003-0147 J9 AM NAT JI Am. Nat. PD NOV PY 2001 VL 158 IS 5 BP 519 EP 529 DI 10.1086/323117 PG 11 WC Ecology; Evolutionary Biology SC Environmental Sciences & Ecology; Evolutionary Biology GA 486ZB UT WOS:000171848300006 PM 18707306 ER PT J AU Bhargava, R Levin, IW AF Bhargava, R Levin, IW TI Fourier transform infrared imaging: Theory and practice SO ANALYTICAL CHEMISTRY LA English DT Article ID PLANE ARRAY DETECTOR; IR; MICROSCOPY; SYSTEMS; SPECTROMETER; MORPHOLOGY; TISSUES; NOISE AB The signal-to-noise ratio (SNR) of spectral data obtained from a microimaging Fourier transform infrared (FT-IR) spectrometer assembly, employing a step-scan interferometer and focal plane array detector, is analyzed. Based on the methodology of data collection, a theoretical description for the performance characteristics is proposed and quantitative effects of the acquisition parameters on the SNR are explained theoretically and compared to experiment. To obtain the best strategy for achieving either the highest SNR in a given time interval or for attaining a given SNR in the shortest time period, the concept of characteristic plots is introduced. The theoretical analysis is extended to Fr-IR microimaging employing continuous scan interferometers in which the advantages of fast image collection are enumerated, while SNR limitations arising from mirror positioning errors are discussed. A step-scan method is suggested for faster data collection in which an optimal detector response and SNR benefits are retained. Theoretically obtained SNRs based upon the expressions proposed in this paper predict experimentally determined values quite well and can be used to obtain an understanding of the required developments for improved performance. Finally, SNRs for both microimaging systems and conventional microspectroscopic instrumentation are compared. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. OI Bhargava, Rohit/0000-0001-7360-994X NR 26 TC 72 Z9 73 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 2001 VL 73 IS 21 BP 5157 EP 5167 DI 10.1021/ac010380m PG 11 WC Chemistry, Analytical SC Chemistry GA 489LH UT WOS:000171992500032 PM 11721913 ER PT J AU Rodriguez-Niedenfuhr, M Papoutsi, M Christ, B Nicolaides, KH von Kaisenberg, CS Tomarev, SI Wilting, J AF Rodriguez-Niedenfuhr, M Papoutsi, M Christ, B Nicolaides, KH von Kaisenberg, CS Tomarev, SI Wilting, J TI Prox1 is a marker of ectodermal placodes, endodermal compartments, lymphatic endothelium and lymphangioblasts SO ANATOMY AND EMBRYOLOGY LA English DT Article DE chick embryo; human fetus; angiogenesis; lymphangiogenesis; endothelium ID GROWTH-FACTOR; VEGF RECEPTOR-3; CELLS; GENE; EXPRESSION; BLOOD; LYMPHANGIOGENESIS; ANGIOGENESIS; PROSPERO; LENS AB The lymphatic endothelium has mostly been thought to be derived by sprouting from specialized veins. Recently it has been shown that mice deficient for the homeobox transcription factor Prox1 are practically devoid of lymphatics. We have studied the expression of Prox1 mRNA and protein in chick embryos and human fetuses. In the chick, Prox1 is expressed in specific compartments of all germ layers. In the ectoderm, it is found in the neural tube, trigeminal, spinal and sympathetic ganglia and the retina, and also in placodal structures such as the lens, olfactory, otic, facial, glossopharyngeal and vagal placodes, and the apical ectodermal ridge. In the endoderm, Prox1 is a marker of hepatocytes, bile duct and pancreatic epithelium. In the mesoderm, weak expression is observed in cardiomyocytes, and strong expression in lymphatic endothelium. Identical expression domains are found in 19-week-old human fetuses. In day 6.5 chick embryos, there are several sites of contact of lymphatics with the jugular vein, which has a mixed endothelium of Prox1-positive and -negative cells. The only non-lymphatic endothelial cells expressing Prox1 are found on the concave side of the cardiac valves. To further analyse development of lymphatics, we studied early chick embryos and observed scattered Prox1-positive cells in the dermatome, giving rise to Prox1-positive lymphatic networks during subsequent development. Furthermore, the anlagen of the posterior lymph sacs and the paired thoracic duct can already be observed in day-4 chick embryos. Our studies show that lymphatics develop much earlier than previously described, and they mostly do not seem to be derived by sprouting from veins. In contrast, lymphangioblasts are present in the deep and superficial compartments of the early mesoderm, independently giving rise to the deep and superficial lymphatics. C1 Univ Freiburg, Inst Anat, D-79104 Freiburg, Germany. Kings Coll London Hosp, Harris Birthright Res Ctr Fetal Med, London, England. Univ Kiel, Frauenklin, D-24105 Kiel, Germany. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wilting, J (reprint author), Univ Freiburg, Inst Anat, Albertstr 17, D-79104 Freiburg, Germany. EM wilting@uni-freiburg.de FU NICHD NIH HHS [N01-HD-6-2915] NR 42 TC 70 Z9 73 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-2061 J9 ANAT EMBRYOL JI Anat. Embryol. PD NOV PY 2001 VL 204 IS 5 BP 399 EP 406 DI 10.1007/s00429-001-0214-9 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 506ZX UT WOS:000173002600004 PM 11789987 ER PT J AU You, WC Zhang, L Pan, KF Jiang, J Chang, YS Perez-Perez, GI Liu, WD Ma, JL Gail, MH Blaser, MJ Fraumeni, JF Xu, GW AF You, WC Zhang, L Pan, KF Jiang, J Chang, YS Perez-Perez, GI Liu, WD Ma, JL Gail, MH Blaser, MJ Fraumeni, JF Xu, GW TI Helicobacter pylori prevalence and CagA status among children in two counties of china with high and low risks of gastric cancer SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE H. pylori; CagA; children; garlic; gastric cancer ID PRECANCEROUS LESIONS; INFECTION; ADENOCARCINOMA; ANTIBODIES; POPULATION; AGE AB BACKGROUND: Studies in adult populations in selected countries with widely varying rates of gastric cancer have shown a weak correlation between gastric cancer mortality rates and the prevalence of CagA+ strains of H. pylori. However, only limited data are available in ethnically homogenous populations with varying rates in the same region. METHODS; We compared the prevalence of H. pylori in general and of CagA+ strains in particular among children in Shandong Province, China in areas at high (Linqu County) and low risk (Cangshan County) of gastric cancer. H. pylori status among children aged 3 to 12 years was determined by C-13-UBT, and CagA status was determined by enzyme-linked immunosorbent assay (ELISA). Because of the difficulty in obtaining blood from young children aged 3 to 4 years and from some children aged 5 years, CagA status was determined among part of children 5 years old and children 6 to 12 years old. RESULTS; Among 98 children aged 3 to 12 years in Linqu, 68 (69.4%) was H. pylori-positive, as compared with 29 (28.7%) among 101 children in Cangshan. Among children positive for C-13-UBT, the proportion of the CagA+ strains were identified was 46 (88.5%) of 52 in Linqu and 13 (81.3%) of 16 in Cangshan, respectively. CONCLUSIONS: The prevalence of H. pylori was nearly three times higher among children in Linqu than in Cangshan, which may contribute to the large differential in gastric cancer rates for two neighboring populations in Shandong Province, (C) 2001 Elsevier Science Inc. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Peking Univ, Beijing Inst Canc Res, Beijing, Peoples R China. Peking Univ, Sch Oncol, Beijing, Peoples R China. Beijing Union Med Coll, Beijing, Peoples R China. Vanderbilt Univ, Ctr Med, Nashville, TN USA. Linqu Publ Hlth Bur, Linqu, Peoples R China. RP You, WC (reprint author), NCI, Div Canc Epidemiol & Genet, EPS Room 8030, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-05613, N01-CP-33041, N01-CP-15620] NR 17 TC 19 Z9 21 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2001 VL 11 IS 8 BP 543 EP 546 DI 10.1016/S1047-2797(01)00227-7 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 491DG UT WOS:000172092300004 PM 11709273 ER PT J AU Merrill, RM Weed, DL AF Merrill, RM Weed, DL TI Measuring the public health burden of cancer in the United States through lifetime and age-conditional risk estimates SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE incidence; life expectancy; life table; malignant neoplasms; mortality; population ID DEVELOPING BREAST-CANCER; GLOBAL BURDEN; DISEASE; DISABILITY; MORTALITY; PROBABILITIES AB PURPOSE: Effects of an aging population in the United States on lifetime and age-conditional risk estimates of developing site-specific cancers are identified and the potential role these statistics play in monitoring disease burden discussed. METHODS: Risk estimates were derived by applying cross-sectional population-based incidence rates of cancer and mortality rates from other causes to a hypothetical cohort. The cohort was aged through a double decrement life table to determine the expected proportion of the population that would develop the disease. RESULTS: Despite black men having higher invasive cancer incidence rates than white men, and black and white women having similar rates, because of the better life expectancy among whites lifetime risk estimates of developing cancer are higher for whites than blacks: 45.5% in white men, 40.4% in black men, 39.2% in white women, and 32.4% in black women based on 1995-97 data. White men experience higher 10-year cancer risk than black men in only bladder cancer, non-Hodgkin's lymphomas (NHL), and leukemia. White women tended to show a greater risk than black women for cancers of the breast, corpus uteri, ovary, NHL, and leukemia. For both whites and blacks, the 10-year risk of lung cancer ranks first among men aged 40, ranks second to prostate cancer for men aged 50, 60, and 70, and ranks second to breast cancer for women aged 40, 50, 60, and 70. CONCLUSIONS: Lifetime and age-conditional risk measures reflect both changes in the disease incidence rates and age distribution over calendar time such that they are useful for monitoring the disease burden in the population. Even if cancer rates remain stable or fall, it is possible for the cancer burden, as reflected by lifetime and age-conditional risk estimates, to increase due to the aging population. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Brigham Young Univ, Dept Hlth Sci, Coll Hlth & Human Performance, Provo, UT 84602 USA. Univ Utah, Coll Med, Dept Family & Prevent Med, Salt Lake City, UT USA. Natl Canc Inst, Off Prevent Oncol, Div Canc Prevent, Rockville, MD USA. RP Merrill, RM (reprint author), Brigham Young Univ, Dept Hlth Sci, Coll Hlth & Human Performance, Provo, UT 84602 USA. RI Peng, Bo/A-6920-2009 OI Peng, Bo/0000-0001-8225-2284 NR 28 TC 23 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2001 VL 11 IS 8 BP 547 EP 553 DI 10.1016/S1047-2797(01)00254-X PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 491DG UT WOS:000172092300005 PM 11709274 ER PT J AU Sharma, S Ghoddoussi, M Gao, P Kelloff, GJ Steele, VE Kopelovich, L AF Sharma, S Ghoddoussi, M Gao, P Kelloff, GJ Steele, VE Kopelovich, L TI A quantitative angiogenesis model for efficacy testing of chemopreventive agents SO ANTICANCER RESEARCH LA English DT Article DE chemopreventive agents; angiogenesis inhibition; chorioallantoic membrane; in vivo model ID VASCULAR INTEGRIN ALPHA(V)BETA(3); GROWTH-FACTOR EXPRESSION; CARCINOMA CELL-LINES; HIGH-DOSE TAMOXIFEN; BREAST-CANCER; RETINOIC ACID; CHICK-EMBRYO; PHASE-II; CHORIOALLANTOIC MEMBRANE; INHIBITS ANGIOGENESIS AB One of the approaches in chemoprevention to prevent or delay the progression of precancerous lesions, is to apply chemopreventive agents that can potentially block angiogenesis. A quantitative in vivo angiogenesis inhibition assay was developed to test the efficacy of twelve chemopreventive agents that represent different chemical classes and multiple biological activities, using the chick chorioallantoic membrane (CAM) model and an oncogene- transfected angiogenic cell line (6 Ti ras/SV myc # 4). These tumorigenic cells held by a primary agarose pellet, were placed alone or with a secondary pellet incorporating five concentrations of the test agent, on an exposed CAM of 7-day-old chick embryo for 72 hours in a humidified chamber at 35degrees C. The cell-induced angiogenic blood vessels, including the microvessels radiating from the cell pellet focal area, were scored using a computerized custom image analysis system The results show that nonsteroidal antiinflammatory drugs (NSAIDS); aspirin, sulindac, sulindac sulfide and sulindac sulfone, were effective inhibitors of cell-induced angiogenesis (23-66%). Aspirin displayed a dose-dependent response with the highest inhibition at 300 muM and an EC50 (the effective molar concentration that inhibits angiogenesis by 50%) of 26muM. Sulindac sulfone was more effective than sulindac with an EC50 of 5 muM versus 85 muM. However sulindac sulfide showed an intermediate response with an EC50 of 41 muM. The retinoids; all-trans-retinoic acid (ATRA), 9-cis-retinoic acid (9cis-RA), and 13-cis-retinoic acid (13-cis-RA) were also highly effective inhibitors of cell-mediated CAM-angiogenesis. 13-cis-RA with an EC50 of 3.6 nM, has been the most efficacious test agent, > 400-fold more effective than 9-cis-RA,4 (1.5 muM). ATRA exhibited an intermediate response between 9-cis-RA and 13-cis-RA with an EC50 of 0.3 muM, and was 100-fold more efficacious than 9-cis-RA. However, the synthetic retinoid, N-(4-hydro.xphenyl) retinamide (4-HPR), was not an effective inhibitor of CAM angiogenesis. Thalidomide, a compound with multiple biological activities, exhibited dose-dependent inhibition ranging-from 10-1000 muM with an EC50 of 19 muM. Other agents that exhibited dose-dependent inhibition included Bowman-Birk inhibitor (BBI), EC50: 10 mug/ml, tamoxifen, EC50. 0.05 muM and difluoromethyl ornithine (DFMO), with an EC50 of 13 muM. These results suggest that tumor-associated angiogenesis can be modulated by non-toxic concentrations of chemopreventive agents representing multiple biological activities and multiple targets. C1 Mantech Environm Technol Inc, Cellular & Mol Toxicol Program, Res Triangle Pk, NC 27709 USA. NCI, Chemoprevent Agent Dev Res Grp, NIH, Bethesda, MD 20892 USA. RP Sharma, S (reprint author), Mantech Environm Technol Inc, Cellular & Mol Toxicol Program, POB 12313, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [N01-CN-85142] NR 70 TC 26 Z9 27 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2001 VL 21 IS 6A BP 3829 EP 3837 PG 9 WC Oncology SC Oncology GA 531ZK UT WOS:000174447000015 PM 11911254 ER PT J AU Hochhut, B Lotfi, Y Mazel, D Faruque, SM Woodgate, R Waldor, MK AF Hochhut, B Lotfi, Y Mazel, D Faruque, SM Woodgate, R Waldor, MK TI Molecular analysis of antibiotic resistance gene clusters in Vibrio cholerae O139 and O1SXT constins SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TRANSFERABLE R-PLASMID; NUCLEOTIDE-SEQUENCE; EL-TOR; DIHYDROFOLATE-REDUCTASE; PASTEURELLA-PISCICIDA; ESCHERICHIA-COLI; TRIMETHOPRIM; INTEGRATION; EPIDEMIC; INTEGRON AB Many recent Asian clinical Vibrio cholerae El Tor O1 and O139 isolates are resistant to the antibiotics sulfamethoxazole (Su), trimethoprim (Tm), chloramphenicol (Cm), and streptomycin (Sm). The corresponding resistance genes are located on large conjugative elements (SXT constins) that are integrated into prfC on the V. cholerae chromosome. We determined the DNA sequences of the antibiotic resistance genes in the SXT constin in MO10, an O139 isolate. In SXTMO10, these genes are clustered within a composite transposon-like structure found near the element's 5' end. The genes conferring resistance to Cm (floR), So (sulII), and Sm (strA and strB) correspond to previously described genes, whereas the gene conferring resistance to Tm, designated dfr18, is novel. In some other O139 isolates the antibiotic resistance gene cluster was found to be deleted from the SXT-related constin. The El Tor O1 SXT constin, SXT ET, does not contain the same resistance genes as SXTMO10. In this constin, the Tin resistance determinant was located nearly 70 kbp away from the other resistance genes and found in a novel type of integron that constitutes a fourth class of resistance integrons. These studies indicate that there is considerable flux in the antibiotic resistance genes found in the SXT family of constins and point to a model for the evolution of these related mobile elements. C1 Tufts Univ, Sch Med, New England Med Ctr, Div Geog Med Infect Dis, Boston, MA 02111 USA. Howard Hughes Med Inst, Boston, MA 02111 USA. Inst Pasteur, Unite Programmat Mol & Toxicol Genet, F-75724 Paris, France. Int Ctr Diarrhoeal Dis Res, Mol Genet Lab, Dhaka 1000, Bangladesh. NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Waldor, MK (reprint author), Tufts Univ, Sch Med, New England Med Ctr, Div Geog Med Infect Dis, Box 041,750 Washington St, Boston, MA 02111 USA. RI Mazel, Didier/F-9200-2013 OI Mazel, Didier/0000-0001-6482-6002 FU NIAID NIH HHS [AI42347, R01 AI042347, R37 AI042347]; NIDDK NIH HHS [P30 DK034928, P30DK-34928] NR 48 TC 188 Z9 211 U1 1 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2001 VL 45 IS 11 BP 2991 EP 3000 DI 10.1128/AAC.45.11.2991-3000.2001 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 483ZC UT WOS:000171664900003 PM 11600347 ER PT J AU Ma, L Kovacs, JA AF Ma, L Kovacs, JA TI Genetic analysis of multiple loci suggests that mutations in the Pneumocystis carinii f. sp hominis dihydropteroate synthase gene arose independently in multiple strains SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SULFONE PROPHYLAXIS; AIDS PATIENTS; REGIONS; PNEUMONIA AB To determine if mutations in the dihydropteroate synthase (DHPS) gene of Pneumocystis carinii f. sp. hominis arose in a single strain that was subsequently widely disseminated, we examined four genomic regions of 22 P. carinii clinical isolates selected based on the absence or presence of mutations in the DHPS gene. By single-strand conformation polymorphism and DNA sequencing, we found varying genotypes for each of the four regions in isolates with DH]PS mutations, suggesting that these mutations occurred independently in multiple strains of P. carinii. This suggests that exposure to sulfa will select for these mutations in diverse strains. C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Ma, L (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 16 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2001 VL 45 IS 11 BP 3213 EP 3215 DI 10.1128/AAC.45.11.3213-3215.2001 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 483ZC UT WOS:000171664900038 PM 11600382 ER PT J AU Goldstein, AM Tucker, MA AF Goldstein, AM Tucker, MA TI Genetic epidemiology of cutaneous melanoma - A global perspective SO ARCHIVES OF DERMATOLOGY LA English DT Review ID MULTIPLE PRIMARY MELANOMAS; FAMILIAL MELANOMA; GERMLINE MUTATIONS; PRONE FAMILIES; CDKN2A MUTATIONS; CDK4; RISK; P53; INHIBITION; KINDREDS C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Goldstein, AM (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Room 7004,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 34 TC 60 Z9 61 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 2001 VL 137 IS 11 BP 1493 EP 1496 PG 4 WC Dermatology SC Dermatology GA 492NH UT WOS:000172174100013 PM 11708953 ER PT J AU Buka, SL Tsuang, MT Torrey, EF Klebanoff, MA Bernstein, D Yolken, RH AF Buka, SL Tsuang, MT Torrey, EF Klebanoff, MA Bernstein, D Yolken, RH TI Maternal infections and subsequent psychosis among offspring SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HERPES-SIMPLEX VIRUS; COLLABORATIVE PERINATAL PROJECT; PRENATAL EXPOSURE; FOLLOW-UP; ADULT SCHIZOPHRENIA; BIPOLAR DISORDER; PREGNANCY; ENCEPHALITIS; INFLUENZA; TYPE-2 AB Background: We tested the hypothesis that maternal infections during pregnancy are associated with the subs equent development of schizophrenia and other psychoses in adulthood. Methods: We conducted a nested case-control study of 27 adults with schizophrenia and other psychotic illnesses and 54 matched unaffected control subjects (matched for sex, ethnicity, and date of birth) from the Providence, RI, cohort of the Collaborative Perinatal Project. We retrieved stored blood samples that had been obtained from these mothers at the end of pregnancy. These samples were analyzed for total class-specific immunoglobulins and for specific antibodies directed at recognized perinatal pathogens capable of affecting brain development. Results: Maternal levels of IgG and IgM class immunoglobulins before the mothers were delivered of their neonates were significantly elevated among the case series (t=3.06, P=.003; t=2.93, P=.004, respectively, for IgG and IgM immunoglobulin-albumin ratios). Secondary analyses indicated a significant association between maternal antibodies to herpes simplex virus type 2 glycoprotein gG2 and subsequent psychotic illness (matched t test=2.43, P=.02). We didn't find significant differences between case and control mothers in the serum levels of IgA class immunoglobulins, or in specific IgG antibodies to herpes simplex Virus type 1, cytomegalovirus, Toxoplasma gondii, rubella virus, human parvovirus B19, Chlamydia trachomatis, or human papillomavirus type 16. Conclusions: The offspring of mothers with elevated levels of total IgG and IgM immunoglobulins and antibodies to herpes simplex virus type 2 are at increased risk for the development of schizophrenia and other psychotic illnesses in adulthood. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. NICHHD, Stanley Res Lab, Bethesda, MD 20892 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Johns Hopkins Univ, Sch Med, Stanley Div Dev Neurovirol, Baltimore, MD USA. RP Buka, SL (reprint author), Harvard Univ, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02115 USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 53 TC 256 Z9 266 U1 2 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2001 VL 58 IS 11 BP 1032 EP 1037 DI 10.1001/archpsyc.58.11.1032 PG 6 WC Psychiatry SC Psychiatry GA 490MR UT WOS:000172056100005 PM 11695949 ER PT J AU Thomas, KM Drevets, WC Dahl, RE Ryan, ND Birmaher, B Eccard, CH Axelson, D Whalen, PJ Casey, BJ AF Thomas, KM Drevets, WC Dahl, RE Ryan, ND Birmaher, B Eccard, CH Axelson, D Whalen, PJ Casey, BJ TI Amygdala response to fearful faces in anxious and depressed children SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 6th International Conference of Functional Mapping of the Human Brain CY JUN 13, 2000 CL SAN ANTONIO, TEXAS ID POSTTRAUMATIC-STRESS-DISORDER; EMOTIONAL FACIAL EXPRESSIONS; SYMPTOM PROVOCATION; MAJOR DEPRESSION; BRAIN ACTIVATION; RECOGNITION; ANXIETY; DAMAGE; FMRI; VOLUMES AB Background: Alterations in amygdala function have been implicated in the pathophysiological characteristics of adult anxiety and depressive disorders. Studies with healthy adults and children, as well as with adults who have amygdala lesions, have found facial expressions of emotion to be useful probes of amygdala activity. Our study examined the amygdala response to fearful and neutral facial expressions in healthy, anxious, and depressed children. We hypothesized that children with anxiety and depression may show atypical amygdala responses to emotional stimuli. Methods: Twelve children (8-16 years of age) with generalized anxiety or panic disorder and 12 healthy comparison children underwent noninvasive functional magnetic resonance imaging while viewing photographs of fearful and neutral facial expressions. In a second comparison, 5 girls with major depressive disorder were compared with 5 anxious and 5 healthy girls from the previous sample. Results: Children with anxiety disorders showed an exaggerated amygdala response to fearful faces compared with healthy children, whereas depressed children showed a blunted amygdala response to these faces. In addition, the magnitude of the amygdala's signal change between fearful and neutral faces was positively correlated with the severity of everyday anxiety symptoms. Conclusions: Our results suggest that amygdala function is affected in both anxiety and depression during childhood and adolescence. Moreover, this disruption appears to be specific to the child's own rating of everyday anxiety. C1 Cornell Univ, Weill Med Coll, Sackler Inst Dev Psychobiol, Dept Psychiat, New York, NY 10021 USA. NIMH, Mood & Anxiety Disorders Neuroimaging Sect, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. RP Thomas, KM (reprint author), Cornell Univ, Weill Med Coll, Sackler Inst Dev Psychobiol, Dept Psychiat, 1300 York Ave,Box 140,Suite F-1332, New York, NY 10021 USA. RI Frank, David/E-8213-2012 FU NIMH NIH HHS [MH 41712] NR 52 TC 331 Z9 332 U1 7 U2 32 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2001 VL 58 IS 11 BP 1057 EP 1063 DI 10.1001/archpsyc.58.11.1057 PG 7 WC Psychiatry SC Psychiatry GA 490MR UT WOS:000172056100009 PM 11695953 ER PT J AU Blackburn, MB Jaffe, H Kochansky, J Raina, AK AF Blackburn, MB Jaffe, H Kochansky, J Raina, AK TI Identification of four additional myoinhibitory peptides (MIPs) from the ventral nerve cord of Manduca sexta SO ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY LA English DT Article DE Manduca sexta; myoinhibitory peptide; myoinhibiting peptide; allatostatin; prothoracicostatin ID JUVENILE-HORMONE BIOSYNTHESIS; BLOWFLY CALLIPHORA-VOMITORIA; GRYLLUS-BIMACULATUS ENSIFERA; DIPLOPTERA-PUNCTATA; COCKROACH ALLATOSTATINS; IMMUNOREACTIVE NEURONS; LOCUSTA-MIGRATORIA; TOBACCO HORNWORM; IN-VITRO; LOM-MIP AB Four new myoinhibitory peptides were isolated and identified from the ventral nerve cord of adult Manduca sexta. The new peptides are related to two previously identified myoinhibitory peptides also isolated from adult M. sexta, Alas-MIP I and Mas-MIP II. The sequences of the new peptides are APEKWAAFHGSWamide (Mas-MIP III), GWNDMSSAWamide (Mas-MIP IV), GWQDMSSAWamide (Mas-MIP V), and AWSALHGAWamide (Mas-MIP VI). Mas-MIPs III-VI were found to inhibit spontaneous peristalsis of the adult M. sexta anterior hindgut (ileum) in vitro. Published 2001 Wiley-Liss, Inc. C1 USDA ARS, PSI, IBL, BARC W,Insect Biocontrol Lab, Beltsville, MD 20705 USA. NINCDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. USDA ARS, BARC E, Bee Res Lab, PSI, Beltsville, MD USA. USDA ARS, So Reg Res Ctr, MSA, Formosan Subterranean Termite Res Unit, New Orleans, LA USA. RP Blackburn, MB (reprint author), USDA ARS, PSI, IBL, BARC W,Insect Biocontrol Lab, Bldg 011A,Rm 214, Beltsville, MD 20705 USA. NR 31 TC 30 Z9 32 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0739-4462 J9 ARCH INSECT BIOCHEM JI Arch. Insect Biochem. Physiol. PD NOV PY 2001 VL 48 IS 3 BP 121 EP 128 DI 10.1002/arch.1064 PG 8 WC Biochemistry & Molecular Biology; Entomology; Physiology SC Biochemistry & Molecular Biology; Entomology; Physiology GA 487PK UT WOS:000171884300002 PM 11673841 ER PT J AU Barontini, M Garcia-Rudaz, MC Veldhuis, JD AF Barontini, M Garcia-Rudaz, MC Veldhuis, JD TI Mechanisms of hypothalamic-pituitary-gonadal disruption in polycystic ovarian syndrome SO ARCHIVES OF MEDICAL RESEARCH LA English DT Review DE adolescents; LH; PCOS; anovulation; hyperandrogenism ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; PULSATILE LUTEINIZING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; GROWTH-FACTOR-I; ANDROGEN NEGATIVE FEEDBACK; PULSE FREQUENCY; CATECHOLAMINE METABOLISM; PUBERTAL DEVELOPMENT; APPROXIMATE ENTROPY AB Although the pathogenesis of polycystic ovarian syndrome (PCOS) is still controversial, a series of investigations has demonstrated an array of neuroendocrine abnormalities as a major component of the syndrome. From a neuroendocrine perspective, patients with PCOS exhibit an accelerated frequency and/or higher amplitude of LH pulses, augmentation of LH secretory burst mass, and a more disorderly LH release. Elevated in vitro LH bioactivity and a preponderance of basic LH isoforms, which correlate positively with elevated serum 17-hydroxyprogesterone, androstenedione, and testosterone concentrations, also characterize adolescents with PCOS. Heightened GnRH drive of gonadotropin secretion and a steroid-permissive milieu appear to jointly promote elevated secretion of basic LH isoforms. Positive feedback is implied, because hypersecretion of highly bioactive LH in PCOS probably contributes to inordinate androgen output. However, the precise nature of feedback disruption remains uncertain. Indeed, recent data suggest that PCOS is marked by anomalies of both feedforward and feedback signaling between GnRH/LH and ovarian androgens. From a single hormone perspective, the individual patterns of LH and androstenedione release are consistently more irregular in patients with PCOS. Bihormonal analysis has disclosed concomitant uncoupling of the pairwise synchrony of LH and testosterone, LH and androstenedione, and testosterone and androstenedione secretion. The foregoing ensemble of findings points to deterioration of both orderly uniglandular and coordinate bihormonal output in PCOS. Additional studies are needed to establish the primary pathophysiologic mechanisms underlying this disorder. (C) 2001 IMSS. Published by Elsevier Science Inc. C1 Hosp Ninos Dr Ricardo Gutierrez, Ctr Invest Endocrinol, RA-1425 Buenos Aires, DF, Argentina. Univ Virginia, Hlth Sci Ctr, Gen Clin Res Ctr,Dept Internal Med, NIH,Ctr Reprod Res,Div Endocrinol, Charlottesville, VA USA. RP Barontini, M (reprint author), Hosp Ninos Dr Ricardo Gutierrez, Ctr Invest Endocrinol, Gallo 1330, RA-1425 Buenos Aires, DF, Argentina. NR 122 TC 28 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0188-4409 J9 ARCH MED RES JI Arch. Med. Res. PD NOV-DEC PY 2001 VL 32 IS 6 BP 544 EP 552 DI 10.1016/S0188-4409(01)00325-3 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 507NC UT WOS:000173033700008 PM 11750729 ER PT J AU Poorkaj, P Tsuang, D Wijsman, E Steinbart, E Garruto, RM Craig, UK Chapman, NH Anderson, L Bird, TD Plato, CC Perl, DP Weiderholt, W Galasko, D Schellenberg, GD AF Poorkaj, P Tsuang, D Wijsman, E Steinbart, E Garruto, RM Craig, UK Chapman, NH Anderson, L Bird, TD Plato, CC Perl, DP Weiderholt, W Galasko, D Schellenberg, GD TI TAU as a susceptibility gene for amyotropic lateral sclerosis-parkinsonism dementia complex of Guam SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; FRONTOTEMPORAL DEMENTIA; LINKAGE DISEQUILIBRIUM; NEURODEGENERATIVE DISORDERS; FTDP-17 MUTATIONS; CHROMOSOME-17; CALCIUM; POLYMORPHISM; METABOLISM; FAMILIES AB Background: A Guam variant of amyotrophic lateral sclerosis (ALS-G) and parkinsonism. dementia complex (PDC-G) are found in the Chamorro people of Guam. Both disorders have overlapping neuropathologic findings, with neurofibrillary tangles in spinal cord and brain. The cause of ALS-G-PDC-G is unknown, although inheritance and environment appear important. Because neurofibrillary tangles containing tau protein are present in ALS-G-PDC-G, and because mutations in the tau gene (TAU) cause autosomal dominant frontotemporal dementia, TAU was examined as a candidate gene for ALS-G-PDC-G. Methods: TAU was evaluated by DNA sequence analysis in subjects with ALS-G-PDC-G, by linkage analysis of TAU polymorphisms in an extended pedigree from the village of Umatac, and by evaluation of linkage disequilibrium with polymorphic markers flanking and within TAU. Results: Linkage disequilibrium between ALS-G-PDC-G and the TAU polymorphism CA3662 was observed. For this 2-allele system, PDC and ALS cases were significantly less likely than Guamanian controls to have the 1 allele (4.9% and 2% vs 11.5%, respectively; Fisher exact P=.007). DNA sequence analysis of TAU coding regions did not demonstrate a mutation responsible for ALS-C-PDC-G. Analysis of TAU genotypes in an extended pedigree of subjects from Umatac showed obligate recombinants between TAU and ALS-G-PDC-G. Linkage analysis of the Umatac pedigree indicates that TAU is not the major gene for ALS-G-PDC-G. Conclusions: The genetic association between ALS-GPDC-G implicates TAU in the genetic susceptibility to ALS-G-PDC-G. TAU may be a modifying gene increasing risk for ALS-G-PDC-G in the presence of another, as yet, unidentified gene. C1 Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle Div, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ Clin Ctr, Seattle Div, Seattle, WA USA. Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. SUNY Binghamton, Dept Anthropol, Binghamton, NY USA. SUNY Binghamton, Dept Biol Sci, Binghamton, NY USA. NINCDS, NIH, Bethesda, MD 20892 USA. Univ Guam, Dept Publ Hlth, Mangilao, GU USA. Univ San Diego, Dept Neurosci, San Diego, CA 92110 USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Mt Sinai Sch Med, Dept Psychol, New York, NY USA. RP Schellenberg, GD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle Div, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU PHS HHS [P010135316] NR 57 TC 48 Z9 49 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2001 VL 58 IS 11 BP 1871 EP 1878 DI 10.1001/archneur.58.11.1871 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 490MH UT WOS:000172055300022 PM 11708997 ER PT J AU Panegyres, PK Toufexis, K Kakulas, BA Cernevakova, L Brown, P Ghetti, B Piccardo, P Dlouhy, SR AF Panegyres, PK Toufexis, K Kakulas, BA Cernevakova, L Brown, P Ghetti, B Piccardo, P Dlouhy, SR TI A new PRNP mutation (G131V) associated with Gerstmann-Straussler-Scheinker disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID CREUTZFELDT-JAKOB DISEASE; PRION PROTEIN GENE AB Background: Gerstmann-Straussler-Scheinker disease is a rare form of prion disease. Objective: To determine the prion mutation in a 51-year-old man without a family history of neurologic disease who died from Gerstmann-Straussler-Scheinker disease. Patient and Methods: The patient was a 51-year-old man who died after a 9-year illness characterized by dementia and eventually ataxia. Neuropathologic studies were performed, the results of which revealed abundant prion protein-immunopositive amyloid plaques in the cerebellum without spongiform degeneration. Results: Genetic analysis of the prion protein gene showed a novel mutation at codon 131 that caused a valine-for-glycine substitution (G131V) and homozygosity at codon 129 (129M). Proteinase K-resistant prion protein was detected by Western blot analysis. Conclusions: This is the first mutation described in the short, antiparallel P-sheet domain of the prion protein. This report highlights the importance of genetic analysis of patients with atypical dementia even in the absence of a family history. C1 Royal Perth Hosp, Dept Neuropathol, Perth, WA 6000, Australia. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. NINCDS, Cent Nervous Syst Studies Lab, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA. RP Panegyres, PK (reprint author), Royal Perth Hosp, Dept Neuropathol, Wellington St, Perth, WA 6000, Australia. RI Toufexis, Katina/A-6173-2012; Toufexis, Katina/D-3042-2012 OI Toufexis, Katina/0000-0002-6514-2988 FU NIA NIH HHS [P30 AG 10133] NR 17 TC 39 Z9 40 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2001 VL 58 IS 11 BP 1899 EP 1902 DI 10.1001/archneur.58.11.1899 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 490MH UT WOS:000172055300026 PM 11709001 ER PT J AU Li, QJ Ashraf, MF Shen, DF Green, WR Stark, WJ Chan, CC O'Brien, TP AF Li, QJ Ashraf, MF Shen, DF Green, WR Stark, WJ Chan, CC O'Brien, TP TI The role of apoptosis in the pathogenesis of Fuchs endothelial dystrophy of the cornea SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID DESCEMETS MEMBRANE; GROWTH-FACTORS; DEATH; FAS; ULTRASTRUCTURE; KERATOCYTES; MODULATION; UVEITIS; LIGAND; CELLS AB Objective: To investigate the potential role of apoptosis in the pathogenesis of Fuchs endothelial dystrophy of the cornea. Methods: Twenty-one corneal buttons from patients with Fuchs dystrophy and 15 control corneas were studied. Apoptosis was assessed by the in situ end-labeling of double-stranded DNA breaks, and by immunohistochemical characterization of cellular markers associated with apoptosis (Fas, FasL, Bcl-2, and Bax). Expression of Bcl-2 and Bax mRNA in the corneal stroma and endothelium was separately analyzed by a semiquantitative reverse transcriptase polymerase chain reaction. Furthermore, cultivated keratocytes generated from diseased corneal buttons and donor rims were exposed to camptothecin, an apoptotic inducer, for 6 and 24 hours. They were then examined for protein and messenger RNA (mRNA) expression of apoptotic regulatory molecules. Results: DNA fragmentation was seen in the epithelium, stroma, and endothelium in 6 of 7 corneas with Fuchs dystrophy. A statistically significant difference was identified in the expression of Bax and its mRNA in the stroma, but not in the endothelium of Fuchs dystrophy corneas. Following exposure to camptothecin, keratocytes from patients with Fuchs dystrophy responded with an increased level of Bax and a low level of Bcl-2. This trend was distinctively different from the response of normal keratocytes. Conclusions: The evidence in this study points to a disease-related disturbance in the regulation of apoptosis in Fuchs dystrophy. Our findings suggest that excessive apoptosis may be an important mechanism in the pathogenesis of Fuchs dystrophy. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. NEI, Immunol Lab, NIH, Bethesda, MD USA. RP O'Brien, TP (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St,Woods Bldg,Rm 255, Baltimore, MD 21205 USA. NR 35 TC 56 Z9 56 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2001 VL 119 IS 11 BP 1597 EP 1604 PG 8 WC Ophthalmology SC Ophthalmology GA 490ML UT WOS:000172055600001 PM 11709009 ER PT J AU Fine, HF Akin, C Hematti, P Butman, J Caruso, RC Csaky, KG Metcalfe, DD Nussenblatt, RB Robinson, MR AF Fine, HF Akin, C Hematti, P Butman, J Caruso, RC Csaky, KG Metcalfe, DD Nussenblatt, RB Robinson, MR TI Presumed choroidal and orbital mastocytosis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID SYSTEMIC MASTOCYTOSIS; CELLS C1 NEI, NIH, Bethesda, MD 20892 USA. RP Robinson, MR (reprint author), NEI, NIH, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 9 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2001 VL 119 IS 11 BP 1716 EP 1719 PG 4 WC Ophthalmology SC Ophthalmology GA 490ML UT WOS:000172055600021 PM 11709028 ER PT J AU Kaschner, S Hansen, A Jacobi, A Reiter, K Monson, NL Odendahl, M Burmester, GR Lipsky, PE Dorner, T AF Kaschner, S Hansen, A Jacobi, A Reiter, K Monson, NL Odendahl, M Burmester, GR Lipsky, PE Dorner, T TI Immunoglobulin V-lambda light chain gene usage in patients with Sjogren's syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTI-DNA AUTOANTIBODIES; B-CELLS; SOMATIC HYPERMUTATION; SELECTIVE INFLUENCES; RHEUMATOID FACTORS; H GENES; SUBSEQUENT SELECTION; MOLECULAR MECHANISMS; SEQUENCE-ANALYSIS AB Objective. To determine whether patients with Sjogren's syndrome (SS) have abnormalities in Ig V-lambda and J(lambda) gene usage, differences in somatic hypermutation, defects in selection, or indications for perturbations of B cell maturation. Methods. Individual peripheral B cells from SS patients were analyzed for their V-lambda gene usage by single-cell polymerase chain reaction amplification of genomic DNA and compared with those from normal controls. Results. Molecular differences from controls in V-lambda-J(lambda) recombination were identified that were reflected by findings in the nonproductive V-lambda repertoire of the patients, including enhanced rearrangement of V(lambda)10A and J(lambda)2/3 gene segments. In addition, a number of abnormalities in the productive repertoire were identified, indicating disordered selection. A greater usage of 4 V-lambda genes (2A2, 2B2, 2C, and 7A), representing 56% of all productive V-lambda rearrangements, was observed, suggesting positive selection of these genes. Overutilization of J(lambda)2/3 and underutilization of J(lambda)7 in both nonproductive and productive V-lambda rearrangements of SS patients compared with controls suggested decreased receptor editing in SS. The mutational frequency did not differ from that in controls, and positive selection of mutations into the productive V gene repertoire was found, similar to that in controls, although mutational targeting toward RGYW/WRCY motifs, typically found in controls, was not found in SS patients. Conclusion. Disturbed regulation of B cell maturation with abnormal selection, defects in editing Ig receptors, and abnormal mutational targeting may contribute to the emergence of autoimmunity in SS. C1 Univ Hosp Charite, Dept Med, D-10098 Berlin, Germany. Univ Texas, SW Med Ctr, Dallas, TX USA. Deutsch Rheumaforschungszentrum, Berlin, Germany. NIAMSD, Bethesda, MD 20892 USA. RP Dorner, T (reprint author), Univ Hosp Charite, Dept Med, Schumannstr 20-21, D-10098 Berlin, Germany. NR 54 TC 21 Z9 22 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2001 VL 44 IS 11 BP 2620 EP 2632 DI 10.1002/1529-0131(200111)44:11<2620::AID-ART442>3.0.CO;2-M PG 13 WC Rheumatology SC Rheumatology GA 498CC UT WOS:000172491400019 PM 11710718 ER PT J AU Drai, D Kafkafi, N Benjamini, Y Elmer, G Golani, I AF Drai, D Kafkafi, N Benjamini, Y Elmer, G Golani, I TI Rats and mice share common ethologically relevant parameters of exploratory behavior SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE phenotyping mouse behavior; locomotor behavior; computerized tracking; open field; dynamic systems; measuring behavior; behavior genetics; balb ID RATTUS-NORVEGICUS; ENVIRONMENT; CONSTRAINTS AB Detailed studies of rat exploratory behavior reveal that it consists of typical behavior patterns having a distinct structure. Recently we have developed interactive software that uses as input the automatically digitized time-series of the animal's location for the visualization, analysis, capturing and quantification of these patterns. We use this software here for the study of BALB/cJtau mouse behavior. The results suggest that a considerable number of rat patterns are also present in the mouse. These ethologically-relevant patterns have a significant potential as a phenotyping tool. (C) 2001 Published by Elsevier Science B.V. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Fac Exact Sci, Dept Stat & OR, IL-69978 Tel Aviv, Israel. Maryland Psychiat Res Inst, Baltimore, MD USA. Natl Inst Drug Abuse, Baltimore, MD USA. RP Golani, I (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. RI Benjamini, Yoav/C-4219-2008 FU NINDS NIH HHS [1R01 NS 40234-01] NR 18 TC 77 Z9 81 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 1 PY 2001 VL 125 IS 1-2 BP 133 EP 140 DI 10.1016/S0166-4328(01)00290-X PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 493VK UT WOS:000172244000019 PM 11682104 ER PT J AU Benjamini, Y Drai, D Elmer, G Kafkafi, N Golani, I AF Benjamini, Y Drai, D Elmer, G Kafkafi, N Golani, I TI Controlling the false discovery rate in behavior genetics research SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE multiple comparisons; exploratory behavior in mice; Bonferroni procedure; FDR ID MULTIPLE TEST PROCEDURES; STATISTICS; ERROR AB The screening of many endpoints when comparing groups from different strains, searching for some statistically significant difference, raises the multiple comparisons problem in its most severe form. Using the 0.05 level to decide which of the many endpoints' differences are statistically significant, the probability of finding a difference to be significant even though it is not real increases far beyond 0.05. The traditional approach to this problem has been to control the probability of making even one such error-the Bonferroni procedure being the most familiar procedure achieving such control. However, the incurred loss of power stemming from such control led many practitioners to neglect multiplicity control altogether. The False Discovery Rate (FDR), suggested by Benjamini and Hochberg [J Royal Stat Soc Ser B 57 (1995) 289], is a new. different, and compromising point of view regarding the error in multiple comparisons. The FDR is the expected proportion of false discoveries among the discoveries, and controlling the FDR goes a long way towards controlling the increased error from multiplicity while losing less in the ability to discover real differences. In this paper we demonstrate the problem in two studies: the study of exploratory behavior [Behav Brain Res (2001)], and the study of the interaction of strain differences with laboratory environment [Science 284 (1999) 1670]. We explain the FDR criterion, and present two simple procedures that control the FDR. We demonstrate their increased power when used in the above two studies. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Tel Aviv Univ, Sackler Fac Exact Sci, Dept Stat & OR, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. Maryland Psychiat Res Inst, Baltimore, MD USA. Natl Inst Drug Abuse, Baltimore, MD USA. RP Benjamini, Y (reprint author), Tel Aviv Univ, Sackler Fac Exact Sci, Dept Stat & OR, IL-69978 Tel Aviv, Israel. RI Benjamini, Yoav/C-4219-2008 FU NINDS NIH HHS [1R01 NS 40234-01] NR 16 TC 1505 Z9 1521 U1 6 U2 63 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 1 PY 2001 VL 125 IS 1-2 BP 279 EP 284 DI 10.1016/S0166-4328(01)00297-2 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 493VK UT WOS:000172244000034 PM 11682119 ER PT J AU McDonald, MP Miller, KM Li, C Deng, C Crawley, JN AF McDonald, MP Miller, KM Li, C Deng, C Crawley, JN TI Motor deficits in fibroblast growth factor receptor-3 null mutant mice SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE fibroblast growth factor; neurotrophic factor; motor behaviour; prepulse inhibition of acoustic startle; gene mutation; behavioural phenotyping; mouse ID PREPULSE INHIBITION; KNOCKOUT MICE; ACHONDROPLASIA; RAT; LOCALIZATION; MUTATIONS; STARTLE; DISEASE; FGFR-3; STRAIN AB Fibroblast growth factor receptor-3 (FGFR-3) regulates aspects of bone development. Mutations in the FGFR-3 gene (Fgfr3) in humans and mice produce vertebral abnormalities and bone deformities. The present study evaluated the behavioural concomitants of the Fgfr3 -/- mutation. Fgfr3 -/- null mutant mice displayed severe impairments of motor abilities as detected on the rotarod, wire hang and open field tests. Absence of prepulse inhibition of acoustic startle was seen at prepulse levels from 74 to 86 dB. The motor deficits appear to be a direct and predicted consequence of the skeletal kyphosis, scoliosis and long bone overgrowth previously reported in Fgfr3 null mutant mice. The behavioural phenotype displayed by these mutant mice complements their anatomical, physiological and biochemical phenotypes, to complete the characterization of the functional outcome of a single gene mutation. Simple, robust behavioural symptoms, such as poor rotarod performance in Fgfr3 knockout mice, can provide useful surrogate markers to evaluate pharmacological treatments and gene therapies for human genetic diseases. (C) 2001 Lippincott Williams & Wilkins. C1 NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. NIDDKD, Biochem & Metab Lab, Bethesda, MD 20892 USA. RP Crawley, JN (reprint author), NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bldg 10 Room 4D11, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 31 TC 8 Z9 8 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD NOV PY 2001 VL 12 IS 6-7 BP 477 EP 486 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 502BJ UT WOS:000172723600009 PM 11742142 ER PT J AU Ranaldi, R Bauco, P McCormick, S Cools, AR Wise, RA AF Ranaldi, R Bauco, P McCormick, S Cools, AR Wise, RA TI Equal sensitivity to cocaine reward in addiction-prone and addiction-resistant rat genotypes SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE cocaine self-administration; strain differences; brain stimulation reward; rat ID DIFFERENTIAL ETHANOL INTAKE; BRAIN-STIMULATION REWARD; FOOD-DEPRIVATION; DOPAMINE RESPONSIVENESS; INTRAVENOUS COCAINE; SELF-STIMULATION; LOW RESPONDERS; WISTAR RATS; BODY-WEIGHT; STRAINS AB Pat genotypes tentatively identified as addiction-prone or addiction-resistant on the basis of alcohol preference and locomotor responsiveness to novelty - Lewis versus Fischer strains and Nijmegen high versus low responder lines differed in time to develop intravenous cocaine self-administration habits, but did not differ in sensitivity to the ability of cocaine reward to summate with lateral hypothalamic brain stimulation reward. Moreover, rats from the Nijmegen low-responder line that initiated self-administration came to do so compulsively and to the same degree as did the Nijmegen high-responder rats. Thus the differences between both sets of genotypes appeared to reflect differences in reactions to the testing situation more than differences in reaction to the reinforcing drug per se. (C) 2001 Lippincott Williams & Wilkins. C1 Concordia Univ, Ctr Studies Behav Neurobiol, Montreal, PQ H3G 1M8, Canada. Univ Nijmegen, Dept Psychoneuropharmacol, Nijmegen, Netherlands. RP Wise, RA (reprint author), NIDA, IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Wise, Roy/A-6465-2012 NR 48 TC 23 Z9 23 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD NOV PY 2001 VL 12 IS 6-7 BP 527 EP 534 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 502BJ UT WOS:000172723600014 PM 11742147 ER PT J AU Bronsert, MR Mead, AN Hen, R Rocha, BA AF Bronsert, MR Mead, AN Hen, R Rocha, BA TI Amphetamine-induced locomotor activation in 5-HT1B knockout mice: effects of injection route on acute and sensitized responses SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE knockout mice; 5-HT1B receptors; amphetamine; behavioural sensitization; locomotion; intraperitoneal injection; intravenous injection ID INDUCED BEHAVIORAL SENSITIZATION; TIME-DEPENDENT SENSITIZATION; INDUCED CONDITIONED ACTIVITY; NUCLEUS-ACCUMBENS; RECEPTOR AGONIST; REPEATED COCAINE; DOPAMINE; STRESS; LACKING; INCREASES AB Knockout mice lacking serotonin(1B) (5-hydroxytryptamine(1B); 5-HT1B) receptors (IBKO) exhibit increased sensitivity to the stimulant and reinforcing effects of indirect dopamine (DA) agonists and are more reactive to mild stressors such as handling and the injection procedures that commonly occur when using the intraperitoneal (i.p.) route of drug administration. Since the intravenous (i.v.) route of administration allows minimal handling and injection-induced stress, the present study was designed to evaluate the effect of the administration route on amphetamine-induced locomotor activation and behavioural sensitization in 1BKO mice. For this purpose, IBKO and wild-type (WT) control mice were administered i.p. or i.v. amphetamine in a within-session design, which allows evaluation of a complete dose-response curve within a single session. The locomotor stimulant effects of i.p. (0.5-4.0 mg/kg) and i.v. (0.6-1.2 mg/kg) amphetamine were investigated both acutely and following repeated treatments (four treatments at 48 h intervals). The results showed that acute i.p. amphetamine injection induced a significant higher horizontal activity peak effect in 1BKO mice, while this difference was less profound after acute i.v. injection. However, repeated i.p. or i.v. administration of amphetamine induced significantly higher locomotion in 1BKO mice. We conclude that the stimulant effects of amphetamine can be influenced by the route of administration in a genotype-dependent manner, and that route of drug administration (and associated variables) should be considered an important factor in studies of psychostimulant action in knockout mice. (C) 2001 Lippincott Williams & Wilkins. C1 Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. Univ Maryland, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. RP Rocha, BA (reprint author), Merck & Co Inc, R80Y-140,126 E Lincoln Ave, Rahway, NJ 07095 USA. NR 40 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD NOV PY 2001 VL 12 IS 6-7 BP 549 EP 555 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 502BJ UT WOS:000172723600017 PM 11795245 ER PT J AU Hendler, RW Dracheva, S AF Hendler, RW Dracheva, S TI Importance of lipids for bacteriorhodopsin structure, photocycle, and function SO BIOCHEMISTRY-MOSCOW LA English DT Review DE bacteriorhodopsin; lipids; photocycle; Triton X-100; purple membranes; reconstitution ID TO-BLUE TRANSITION; PROTON TRANSLOCATION; CYTOPLASMIC SURFACE; PURPLE MEMBRANE; NATIVE LIPIDS; ASPARTIC-ACID; ACTINIC LIGHT; INTERMEDIATE; STATE; BEHAVIOR AB This review begins with a brief history of early studies on the involvement of lipids in certain bacteriorhodopsin (BR) properties. Such properties include the regulation of the pK for the purple to blue transition caused by deionization, and the reformation of trimers from monomers after exposure of the purple membrane to Triton X-100. Most of the review is devoted to newer studies which indicate an important role for the neutral lipid squalene in the functional stability of the fast-decaying M-intermediate, for its decay through a pathway involving the O-intermediate, and for the regulation of the relative amounts of slow-decaying and fast-decaying forms of M. Participation of a peripheral acidic amino acid in the overall expression of fast-decaying M is also discussed. Initial studies suggest that the acidic amino acid may be Asp36 and/or Asp38. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hendler, RW (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 31 TC 10 Z9 10 U1 1 U2 8 PU MAIK NAUKA/INTERPERIODICA PI NEW YORK PA C/O KLUWER ACADEMIC-PLENUM PUBLISHERS, 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0006-2979 J9 BIOCHEMISTRY-MOSCOW+ JI Biochem.-Moscow PD NOV PY 2001 VL 66 IS 11 BP 1311 EP 1314 DI 10.1023/A:1013143621346 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 507WN UT WOS:000173054400013 PM 11743875 ER PT J AU Knutson, B Momenan, R Rawlings, RR Fong, GW Hommer, D AF Knutson, B Momenan, R Rawlings, RR Fong, GW Hommer, D TI Negative association of neuroticism with brain volume ratio in healthy humans SO BIOLOGICAL PSYCHIATRY LA English DT Article DE stress; neuroticism; personality; brain volume; intracranial volume; magnetic resonance imaging ID INTRACRANIAL VOLUME; HIPPOCAMPAL VOLUME; MOOD DISORDERS; STRESS; PERSONALITY; TRAITS; MR; ABNORMALITIES; CHILDHOOD; DISEASE AB Background: Brain volume decreases with normal aging. We sought to determine whether, in addition to age, individual differences in stress reactivity (i.e., neuroticism) would also predict reductions in brain volume. Methods: Brain volume ratios were calculated for a sample of 86 healthy volunteers, based on segmented brain volumes taken from T-1-weighted magnetic resonance imaging and corrected for intracranial volume. Standardized self-reported measures of dispositional neuroticism were concurrently obtained by administering the Revised NEO Personality Inventory. Results: After statistically controlling for age and sex, neuroticism showed a significant negative association with the ratio of brain to the remainder of the intracranial volume, but was not related to intracranial volume itself. In particular, subfactors of neuroticism related to the chronic experience of arousing negative emotions were associated with reduced brain ratio. Conclusions: These results suggest that individual differences in stress reactivity contribute to reductions in brain volume observed during adulthood. (C) 2001 Society of Biological Psychiatry. C1 NIH, NIAAA, Clin Studies Lab, Sect Brain Imaging & Electrophysiol, Bethesda, MD 20892 USA. RP Knutson, B (reprint author), NIH, NIAAA, Clin Studies Lab, Sect Brain Imaging & Electrophysiol, 12 Ctr Dr,MSC 1610,Bldg 10,Room 6S240, Bethesda, MD 20892 USA. OI Knutson, Brian/0000-0002-7669-426X NR 38 TC 59 Z9 60 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2001 VL 50 IS 9 BP 685 EP 690 DI 10.1016/S0006-3223(01)01220-3 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 490DL UT WOS:000172035100005 PM 11704075 ER PT J AU Pine, DS Cohen, P Brook, J AF Pine, DS Cohen, P Brook, J TI Adolescent fears as predictors of depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anxiety; depression; prospective research; epidemiology ID DISORDERS; ANXIETY; CHILDREN; PARENTS; RISK AB Background: Recent studies raise questions on the relationship between adolescent fears and risk for major depression. Methods: An epidemiologic sample of 776 young people received psychiatric assessments in 1983, 1985-1986, and 1992. Prospective associations were examined between fears in adolescence and future episodes of major depression. Results: Both overall level of fears and specific fear of dark in adolescence predicted future risk for major depression. Conclusions: Relatively high levels of fear in adolescence represent a risk factor for later episodes of major depression. (C) 2001 Society of Biological Psychiatry. C1 NIMH, Intramural Res Program, Program Mood & Anxiety Disorders, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. New York State Psychiat Inst & Hosp, Div Epidemiol Mental Disorders, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. RP Pine, DS (reprint author), NIMH, Intramural Res Program, Program Mood & Anxiety Disorders, Bldg 10,Room 4N222, Bethesda, MD 20892 USA. FU NIDA NIH HHS [DA-03188, K05-DA-00244]; NIMH NIH HHS [K20-MH01391, MH 36971] NR 13 TC 50 Z9 50 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2001 VL 50 IS 9 BP 721 EP 724 DI 10.1016/S0006-3223(01)01238-0 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 490DL UT WOS:000172035100010 PM 11704080 ER PT J AU Graf, A Wallner, C Schubert, V Willeit, M Wlk, W Fischer, P Kasper, S Neumeister, A AF Graf, A Wallner, C Schubert, V Willeit, M Wlk, W Fischer, P Kasper, S Neumeister, A TI The effects of light therapy on mini-mental state examination scores in demented patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE light therapy; vascular dementia; alzheimer-type dementia; body temperature; cognitive functions ID REST-ACTIVITY RHYTHM; BRIGHT LIGHT; ALZHEIMERS-DISEASE; DISTURBANCES; DISORDERS AB Background: Preliminary evidence suggests that demented patients may experience beneficial effects of light therapy. The authors tested whether bright light therapy (BLT) is capable of improving cognitive functions in patients with Alzheimer-type dementia (AD) or vascular dementia (VD). Methods: Twenty-three patients with AD or VD were randomly assigned to either evening BLT or dim light therapy (DLT). Effects of light therapy on cognitive functions were assessed before and after light therapy using Mini-Mental State Examination (MUSE) scores. Body temperature rhythm (BTR) was additionally recorded pre- and posttreatment. Results: Irrespective of their diagnosis, patients treated with BLT (p =.0012) but not with DLT (p =.73) showed a statistically significant increase in MMSE total scores after light therapy. Evening BLT simultaneously induced a significant phase delay of 56 min on BTR (p =.025). Conclusions: Our preliminary results suggest that shortterm evening BLT may exert beneficial effects on cognitive functioning in patients with dementia. 2001 Society of Biological Psychiatry. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Vienna, Dept Gen Psychiat, Vienna, Austria. RP Neumeister, A (reprint author), NIMH, Mood & Anxiety Disorders Program, 9000 Rockville Pike,Bldg 1-B3-10, Bethesda, MD 20892 USA. NR 8 TC 31 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2001 VL 50 IS 9 BP 725 EP 727 DI 10.1016/S0006-3223(01)01178-7 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 490DL UT WOS:000172035100011 PM 11704081 ER PT J AU Bezrukov, SM Kasianowicz, JJ AF Bezrukov, SM Kasianowicz, JJ TI Neutral polymers in the nanopores of alamethicin and alpha-hemolysin SO BIOLOGICHESKIE MEMBRANY LA English DT Article ID SINGLE-ION CHANNEL; PORE; MEMBRANES; CONDUCTANCE; STATES AB The ability of polymers to enter nanometer-scale pores can be probed by ionic channel conductance measurements because the movement of neutral polymer (e.g. poly(ethylene glycol), PEG) into the channel displaces ions and reduces their mobility in the pore. Both result in a reduction of the channel's conductance. Therefore, the state of occupancy of the pore by polymer is reflected by the conductance which we use to determine the polymer partition coefficient. We conclude that the available theoretical approaches to the entropic interaction between polymer and a pore (hard spheres, random flight model, and scaling theory) do not describe the equilibrium partitioning of PEG into alamethicin and a-hemolysin. The empirically obtained partition coefficients for these two channels demonstrate a much sharper dependence on polymer molecular weight. C1 NICHHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. NIST, Div Biotechnol, Gaithersburg, MD 20899 USA. RP Bezrukov, SM (reprint author), NICHHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. NR 22 TC 7 Z9 7 U1 0 U2 2 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0233-4755 J9 BIOL MEMBRANY JI Biol. Membr. PD NOV-DEC PY 2001 VL 18 IS 6 BP 453 EP 457 PG 5 WC Cell Biology SC Cell Biology GA 522BE UT WOS:000173875200005 ER PT J AU Chernomordik, LV Melikyan, GB AF Chernomordik, LV Melikyan, GB TI Membrane fusion and ten reasons not to study it SO BIOLOGICHESKIE MEMBRANY LA English DT Review ID INFLUENZA-VIRUS HEMAGGLUTININ; INDUCED CONFORMATIONAL-CHANGES; CELL-CELL FUSION; SIMIAN IMMUNODEFICIENCY VIRUS; PLANAR BILAYER-MEMBRANES; COILED-COIL REGION; ENVELOPE GLYCOPROTEIN; ELECTRON-MICROSCOPY; MEDIATED FUSION; LIPID BILAYERS AB Tightly controlled, highly localized, and, in many cases, amazingly rapid remodeling of membranes plays a central role in diverse normal and pathological processes in any living cell. Even in the case of fusion mediated by viral envelope glycoproteins, where the fusogenic proteins are often reliably identified and characterized, the specific protein-lipid interplay underlying fusion of two lipid bilayers into one remains unknown. Here we discuss methodological approaches, phenomenology and hypothetical mechanisms of biological fusion as well as some limitations of the current "fusionology". C1 NICHHD, Sect Membrane Biol, NIH, Gaithersburg, MD 20899 USA. Rush Med Coll, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA. RP Chernomordik, LV (reprint author), NICHHD, Sect Membrane Biol, NIH, Bldg 10,Rm 10D04,10 Ctr Dr, Gaithersburg, MD 20899 USA. NR 126 TC 0 Z9 0 U1 0 U2 3 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0233-4755 J9 BIOL MEMBRANY JI Biol. Membr. PD NOV-DEC PY 2001 VL 18 IS 6 BP 477 EP 488 PG 12 WC Cell Biology SC Cell Biology GA 522BE UT WOS:000173875200008 ER PT J AU Brown, LL Pavlova, O Mukhin, A Kimes, AS Horti, AG AF Brown, LL Pavlova, O Mukhin, A Kimes, AS Horti, AG TI Radiosynthesis of 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-[C-11]methyl-2-(S)-pyrrolidinylme thoxy)pyridine, a high affinity ligand for studying nicotinic acetylcholine receptors by positron emission tomography SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID IN-VIVO TRACER; SCHIZOPHRENIA; BINDING; FLUORINE-18-FPH; EPIBATIDINE; RADIOTRACER; ANALOG AB 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)pyridine (1b) exhibited high affinity for nicotinic acetylcholine receptors in the in vitro competition binding assays, with a K-d value in the low picomolar range, performed at room temperature and at physiological temperature. An efficient radiochemical synthesis of 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-[C-11]methyl-2-(S)-pyrrolidinylmethoxy)pyridine (1c), a potential tracer for the study of nAChR by positron emission tomography, has been developed. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NIDA, Brain Imaging Ctr, NIH, Baltimore, MD 21224 USA. RP Brown, LL (reprint author), NIDA, Brain Imaging Ctr, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 24 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV PY 2001 VL 9 IS 11 BP 3055 EP 3058 DI 10.1016/S0968-0896(01)00224-3 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 485KF UT WOS:000171753000035 PM 11597489 ER PT J AU Iwasa, KH AF Iwasa, KH TI A two-state piezoelectric model for outer hair cell motility SO BIOPHYSICAL JOURNAL LA English DT Article ID ACTIVE FORCE GENERATION; GUINEA-PIG; MEMBRANE MOTOR; COCHLEAR AMPLIFIER; CAPACITANCE; FREQUENCY; CHARGE; MECHANISM; STIFFNESS; CURRENTS AB Recent studies have revealed that voltage-dependent length changes of the outer hair cell are based on charge transfer across the membrane. Such a motility can be explained by an "area motor" model, which assumes two states in the motor and that conformational transitions involve transfer of motor charge across the membrane and mechanical displacements of the membrane. Here It is shown that the area motor is piezoelectric and that the hair cell that incorporates such a motor in its lateral membrane is also piezoelectric. Distinctive features of the outer hair cell are its exceptionally large piezoelectric coefficient, which exceeds the best known piezoelectric material by four orders of magnitude, and its prominent nonlinearity due to the discreteness of motor states. C1 NIDOCD, Biophys Sect, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), NIDOCD, Biophys Sect, Lab Cellular Biol, NIH, Bldg 50,Rm 4152,50 South Dr,MSC-8027, Bethesda, MD 20892 USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 47 TC 47 Z9 47 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2001 VL 81 IS 5 BP 2495 EP 2506 PG 12 WC Biophysics SC Biophysics GA 485LE UT WOS:000171755200006 PM 11606265 ER PT J AU Harms, GS Cognet, L Lommerse, PHM Blab, GA Kahr, H Gamsjager, R Spaink, HP Soldatov, NM Romanin, C Schmidt, T AF Harms, GS Cognet, L Lommerse, PHM Blab, GA Kahr, H Gamsjager, R Spaink, HP Soldatov, NM Romanin, C Schmidt, T TI Single-molecule imaging of L-type Ca2+ channels in live cells SO BIOPHYSICAL JOURNAL LA English DT Article ID GREEN FLUORESCENT PROTEIN; CALCIUM CHANNELS; CORRELATION SPECTROSCOPY; DIHYDROPYRIDINE RECEPTORS; LATERAL DIFFUSION; ALPHA(1C) SUBUNIT; LIVING CELLS; MEMBRANE; DYNAMICS; EXCITATION AB L-type Ca2+ channels are an important means by which a cell regulates the Ca2+ influx into the cytosol on electrical stimulation. Their structure and dynamics in the plasma membrane, including their molecular mobility and aggregation, is of key interest for the in-depth understanding of their function. Construction of a fluorescent variant by fusion of the yellow-fluorescent protein to the ion channel and expression in a human cell line allowed us to address its dynamic embedding in the membrane at the level of individual channels in vivo. We report on the observation of individual fluorescence-labeled human cardiac L-type Ca2+ channels using wide-field fluorescence microscopy in living cells. Our fluorescence and electrophysiological data indicate that L-type Ca2+ channels tend to form larger aggregates which are mobile in the plasma membrane. C1 Leiden Univ, Dept Biophys, NL-2333 CA Leiden, Netherlands. Leiden Univ, Dept Biol, NL-2333 CA Leiden, Netherlands. Univ Linz, Inst Biophys, A-4040 Linz, Austria. NIA, NIH, Baltimore, MD 21224 USA. RP Schmidt, T (reprint author), Huygens Lab, Niels Bohrweg 2, NL-2333 AC Leiden, Netherlands. RI Schmidt, Thomas/B-6296-2009; Cognet, Laurent/F-4163-2011; Blab, Gerhard/D-2275-2011; Romanin, Christoph/D-5399-2009; OI Schmidt, Thomas/0000-0002-0045-1851; Cognet, Laurent/0000-0002-3573-5387; Romanin, Christoph/0000-0003-3756-4136; Gamsjaeger, Roland/0000-0003-1095-2569 NR 44 TC 134 Z9 138 U1 1 U2 9 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2001 VL 81 IS 5 BP 2639 EP 2646 PG 8 WC Biophysics SC Biophysics GA 485LE UT WOS:000171755200018 PM 11606277 ER PT J AU Kawabata, H Nakamaki, T Ikonomi, P Smith, RD Germain, RS Koeffler, HP AF Kawabata, H Nakamaki, T Ikonomi, P Smith, RD Germain, RS Koeffler, HP TI Expression of transferrin receptor 2 in normal and neoplastic hematopoietic cells SO BLOOD LA English DT Article ID MOLECULAR-CLONING; LEUKEMIA; GENE; LINE; HEMOCHROMATOSIS AB Iron is essential for cell proliferation, heme synthesis, and a variety of cellular metabolic processes. In most cells, transferrin receptor-mediated endocytosis is a major pathway for cellular iron uptake. Recently, transferrin receptor 2 (TfR2), another receptor for transferrin, was cloned. High levels of expression of TfR2 messenger RNA (mRNA) occur in the liver, as well as in HepG2 (a hepatoma cell line) and K562 (an erythroid leukemia cell line). In this study, TfR2 mRNA expression was analyzed in hematological cell lines, normal erythroid cells at various stages of differentiation, and leukemia and preleukemia cells. High levels of TfR2 expression occurred in all of the erythroid cell lines that were examined. Erythroid-specific expression of TfR2 protein in bone marrow cells was confirmed by immunohistochemical staining. Expression of TfR2 mRNA was high in normal CD34(+) erythroid precursor cells, and levels decreased during erythroid differentiation in vitro. Levels of expression of TfR2-alpha mRNA were significantly higher in erythroleukemia (M6) marrow samples than in nonmalignant control marrow samples. In addition, relatively higher levels of TfR2-alpha mRNA expression occurred In some samples of myelodysplastic syndrome that had erythroid hyperplasia in bone marrow, acute myelogenous leukemia M1, M2, and chronic myelogenous leukemia. Expression profiles of normal members of the erythroid lineage suggest that TfR2-alpha may be a useful marker of early erythroid precursor cells. The clinical significance of TfR2-alpha expression in leukemia cells remains to be determined. (C) 2001 by The American Society of Hematology. C1 Univ Calif Los Angeles, Sch Med, Burns & Allen Res Inst,Div Hematol Oncol, Cedars Sinai Med Ctr,Dept Med, Los Angeles, CA 90024 USA. Showa Univ, Sch Med, Dept Hematol, Tokyo 142, Japan. Kanazawa Med Univ, Div Hematol Immunol, Uchinada, Ishikawa, Japan. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Koeffler, HP (reprint author), Univ Calif Los Angeles, Sch Med, Burns & Allen Res Inst,Div Hematol Oncol, Cedars Sinai Med Ctr,Dept Med, Los Angeles, CA 90024 USA. NR 21 TC 77 Z9 81 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2001 VL 98 IS 9 BP 2714 EP 2719 DI 10.1182/blood.V98.9.2714 PG 6 WC Hematology SC Hematology GA 487CK UT WOS:000171855900018 PM 11675342 ER PT J AU Piekarz, RL Robey, R Sandor, V Bakke, S Wilson, WH Dahmoush, L Kingma, DM Turner, ML Altemus, R Bates, SE AF Piekarz, RL Robey, R Sandor, V Bakke, S Wilson, WH Dahmoush, L Kingma, DM Turner, ML Altemus, R Bates, SE TI Inhibitor of histone deacetylation, depsipeptide (FR901228), in the treatment of peripheral and cutaneous T-cell lymphoma: a case report SO BLOOD LA English DT Article ID CHROMOBACTERIUM-VIOLACEUM NO-968; CANCER; CLASSIFICATION; EXPRESSION; LEUKEMIA AB Depsipeptide, FR901228, has demonstrated potent in vitro and in vivo cytotoxic activity against murine and human tumor cell lines. In the laboratory, it has been shown to be a histone deacetylase (HDAC) inhibitor. In a phase I trial of depsipeptide conducted at the National Cancer Institute, 3 patients with cutaneous T-cell lymphoma had a partial response, and 1 patient with peripheral T-cell lymphoma, unspecified, had a complete response. Sezary cells isolated from patients after treatment had increased histone acetylation. These results suggest that inhibition of HDAC is a novel and potentially effective therapy for patients with T-cell lymphoma. (C) 2001 by The American Society of Hematology. C1 NCI, Med Branch, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Piekarz, RL (reprint author), 9000 Rockville Pike,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. NR 19 TC 357 Z9 365 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2001 VL 98 IS 9 BP 2865 EP 2868 DI 10.1182/blood.V98.9.2865 PG 4 WC Hematology SC Hematology GA 487CK UT WOS:000171855900040 PM 11675364 ER PT J AU Noguchi, CT Gladwin, M Diwan, B Merciris, P Smith, R Yu, XB Buzard, G Fitzhugh, A Keefer, LK Schechter, AN Mohandas, N AF Noguchi, CT Gladwin, M Diwan, B Merciris, P Smith, R Yu, XB Buzard, G Fitzhugh, A Keefer, LK Schechter, AN Mohandas, N TI Pathophysiology of a sickle cell trait mouse model: Human alpha beta(S) transgenes with one mouse beta-globin allele SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE sickle cell trait; pathophysiology; transgenic mouse; kidney pathology; oxygen affinity ID RENAL MEDULLARY CARCINOMA; THALASSEMIC MICE; HEMOGLOBIN; DISEASE; POLYMERIZATION; ABNORMALITIES; NEPHROPATHY AB As a potential model for sickle cell trait (AS), we examined mice containing one normal mouse beta-globin allele in combination with a human hemoglobin S (halphabeta(S)) transgene (mbeta/hS). The mice segregated into two subpopulations containing low and high proportions of hemoglobin S (mbeta/hS1 and mbeta/hS2, respectively) that was associated with one or two human halphabeta(S) transgenes. We noted striking kidney pathology (cortical cysts, hyperplastic tubules, and glomerulonephritis), increasing with age and with greater severity in mbeta/hS1. mbeta/hS2 animals were largely tolerant to 5% O-2 for 1 h, whereas 80% of mbeta/hS1 mice died, exhibiting acute sequestration of erythrocytes in spleen, liver, and heart. These pathologies appear to result from a decreased oxygen affinity of the hybrid (human alpha/mouse beta) hemoglobins with a mild beta-thalassemia phenotype. Thus, these mouse models of sickle trait seem to manifest their renal pathology and sensitivity to hypoxia by mechanisms related to low tissue oxygen delivery and are different from the human syndrome. Analyses of parameters such as P-50, red cell indices, and genetic background are necessary in establishing potential relevance of any mouse model of the sickle cell syndromes. C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, CC, Bethesda, MD 20892 USA. NCI, Intramural Res Support Program, SAIC, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. RP Noguchi, CT (reprint author), NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RI Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Schechter, Alan N/0000-0002-5235-9408 FU NCI NIH HHS [N01-CO-56000]; NHLBI NIH HHS [HL31579] NR 25 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD NOV-DEC PY 2001 VL 27 IS 6 BP 971 EP 977 DI 10.1006/bcmd.2001.0469 PG 7 WC Hematology SC Hematology GA 523VD UT WOS:000173977200002 PM 11831863 ER PT J AU Berardelli, A Rothwell, JC Thompson, PD Hallet, M AF Berardelli, A Rothwell, JC Thompson, PD Hallet, M TI Pathophysiology of bradykinesia in Parkinson's disease SO BRAIN LA English DT Review DE bradykinesia; Parkinson's disease; movement; motor control ID MOVEMENT-RELATED POTENTIALS; SUPPLEMENTARY MOTOR AREA; CHOICE-REACTION-TIME; CONTINGENT NEGATIVE-VARIATION; POSITRON EMISSION TOMOGRAPHY; TRANSCRANIAL MAGNETIC STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION; SEQUENTIAL FINGER MOVEMENTS; CEREBRAL BLOOD-FLOW; BASAL GANGLIA AB Bradykinesia means slowness of movement and is one of the cardinal manifestations of Parkinson's disease. Weakness, tremor and rigidity may contribute to but do not fully explain bradykinesia. We argue that bradykinesia results from a failure of basal ganglia output to reinforce the cortical mechanisms that prepare and execute the commands to move. The cortical deficit is most apparent in midline motor areas. This leads to particular difficulty with self-paced movements, prolonged reaction times and abnormal pre-movement EEG activity. Movements are often performed with normally timed EMG bursts but the amount of EMG activity is underscaled relative to the desired movement parameters. There are also abnormalities in sensory scaling and sensorimotor integration. The brain appears to be able to compensate to some degree for the basal ganglia deficit. There is overactivity in the lateral premotor areas during task performance and movements can be speeded by giving sensory cues. Attention to movement is also beneficial. However, we propose that the engagement of compensatory processes may also lead to reduced performance in other tasks. For example, patients' problems in performing more than one task at the same time could result from lack of sufficient resources both to compensate for their basal ganglia deficit and to run two tasks simultaneously. Surgical therapies are unlikely to work solely by normalizing basal ganglia output to that seen in healthy individuals. It seems more plausible that surgery removes an interfering signal that allows more efficient compensation by other structures. C1 Univ Roma La Sapienza, IRCCS, Ist Neurol Neuromed, Dipartimento Sci Neurol, I-00185 Rome, Italy. Inst Neurol, MRC, Human Movement & Balance Unit, London WC1N 3BG, England. Univ Adelaide, Dept Med, Royal Adelaide Hosp, Adelaide, SA 5001, Australia. NINCDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Berardelli, A (reprint author), Univ Roma La Sapienza, IRCCS, Ist Neurol Neuromed, Dipartimento Sci Neurol, Viale Univ 30, I-00185 Rome, Italy. OI Rothwell, John/0000-0003-1367-6467 NR 138 TC 323 Z9 332 U1 3 U2 28 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2001 VL 124 BP 2131 EP 2146 DI 10.1093/brain/124.11.2131 PN 11 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 494QC UT WOS:000172295500002 PM 11673316 ER PT J AU Schmidt, E Skrobek, C Kromminga, A Hashimoto, T Messer, G Brocker, EB Yancey, KB Zillikens, D AF Schmidt, E Skrobek, C Kromminga, A Hashimoto, T Messer, G Brocker, EB Yancey, KB Zillikens, D TI Cicatricial pemphigoid: IgA and IgG autoantibodies target epitopes on both intra- and extracellular domains of bullous pemphigoid antigen 180 SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE bullous disease; epitope; LAD-1; laminin-5; NC16A; subepidermal ID BETA-4 INTEGRIN SUBUNIT; INTRACELLULAR DOMAINS; SOLUBLE ECTODOMAIN; BP180 ECTODOMAIN; SKIN DISEASES; XVII COLLAGEN; DERMATOSIS; REACT; HEMIDESMOSOMES; KERATINOCYTES AB Background Cicatricial pemphigoid (CP) is an autoimmune subepidermal blistering disease where autoantibodies target various components of the dermal-epidermal junction, including the bullous pemphigoid antigen 180 (BP180). Objective We determined the exact specificity of circulating IgG and IgA autoantibodies to BP180 in a large number of CP patients. Methods Twenty-six consecutive CP sera were analysed by Western blotting using a panel of cell-derived and recombinant proteins covering the entire BP180 molecule. Results Circulating autoantibodies were detected in all CP sera. Seven sera reacting with laminin-5 were excluded from further analyses; the remaining 19 sera recognized BP180, including six sera (32%) that showed only IgA reactivity to this protein. With the combined use of the soluble BP180 ectodomain (LAD-1) and recombinant BP180 NC16A, 16 of these 19 CP sera (84%) targeted BP180. IgG reactivity was preferentially found against NC16A, whereas IgA antibodies predominantly recognized LAD-1. Thirty-two per cent of the BP180-reative sera revealed reactivity with the intracellular domain of this protein. Conclusions Our findings demonstrate that autoantibodies in CP target epitopes on both extra- and intracellular domains of BP180 and highlight the importance of testing for both IgG and IgA reactivity in these patients' sera. C1 Univ Wurzburg, Dept Dermatol, D-97080 Wurzburg, Germany. Inst Immunol Pathol & Mol Biol, Hamburg, Germany. Kurume Univ, Sch Med, Fukuoka, Japan. Univ Munich, Dept Dermatol, D-8000 Munich, Germany. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Zillikens, D (reprint author), Univ Wurzburg, Dept Dermatol, Josef Schneider Str 2, D-97080 Wurzburg, Germany. RI Schmidt, Enno/C-4008-2009; Zillikens, Detlef/C-8572-2011 OI Schmidt, Enno/0000-0002-1206-8913; NR 36 TC 47 Z9 48 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 2001 VL 145 IS 5 BP 778 EP 783 DI 10.1046/j.1365-2133.2001.04471.x PG 6 WC Dermatology SC Dermatology GA 495LJ UT WOS:000172342400012 PM 11736901 ER PT J AU Hagan, JJ Vorel, SR Ashby, CR Paul, M Liu, XH Hayes, R Middlemiss, DN Gardner, EL AF Hagan, JJ Vorel, SR Ashby, CR Paul, M Liu, XH Hayes, R Middlemiss, DN Gardner, EL TI The role of dopamine D-3 receptors in drug abuse SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 GlaxoSmithKline, Psychiat Ctr Excellence Drug Discovery, Verona, Italy. NIDA, Intramural Res Program, Baltimore, MD USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Eon Labs, Laurelton, NY USA. St Johns Univ, Jamaica, NY 11439 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD NOV PY 2001 VL 134 SU S MA 199P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 496AK UT WOS:000172372400199 ER PT J AU Canto, MT Anderson, WF Brawley, O AF Canto, MT Anderson, WF Brawley, O TI Geographic variation in breast cancer mortality for white and black women: 1986-1995 SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID SURVIVAL; RATES; US AB Breast cancer mortality rates have decreased during the last 20 years in the United States overall. However, declines in breast cancer mortality rates differ among individual states. This analysis ranked states from the highest to the lowest percentage change in mortality between 1986 to 1990 and 1991 to 1995. Data on white and black females were analyzed separately. Among white women, the 10 states showing the greatest percentage change in mortality during those two periods had the greatest baseline mortality in the 1986-to-1990 period. Similarly, the 10 states with the lowest percentage change in mortality had the lowest mortality rate in 1986 to 1990. In contrast, among black women, the top 10 states ranked by percentage change in mortality included either a decline or an increase. The disparities in mortality rates by state likely depend on the stage of disease at diagnoses, socioeconomic status, access to care, and adequacy of medical care. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NCI, Off Special Populat Res, Div Canc Prevent, Bethesda, MD USA. RP Canto, MT (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD NOV-DEC PY 2001 VL 51 IS 6 BP 367 EP 370 PG 4 WC Oncology SC Oncology GA 488ZN UT WOS:000171967400005 PM 11760571 ER PT J AU Demers, RY Tiwari, A Wei, J Weiss, LK Severson, RK Montie, J AF Demers, RY Tiwari, A Wei, J Weiss, LK Severson, RK Montie, J TI Trends in the utilization of androgen-deprivation therapy for patients with prostate carcinoma suggest an effect on mortality SO CANCER LA English DT Article DE prostate carcinoma; hormones; mortality; surveillance; epidemiology; and end results (SEER) Program ID CANCER SURVEILLANCE SERIES; DETROIT METROPOLITAN-AREA; RADICAL PROSTATECTOMY; INTERPRETING TRENDS; RADIATION-THERAPY; ANTIGEN; GUIDELINES; FLUTAMIDE; DIAGNOSIS; SURVIVAL AB BACKGROUND. After a surge in the incidence of prostate carcinoma in the early 1990s, diminishing rates of mortality became apparent in 1993. This decrease in mortality is unlikely to be explained entirely by treatment with curative intent alone following screen-detected cases, because the time frame between detection and mortality remains relatively brief. METHODS. This study used incidence and initial treatment data from the Detroit area SEER registry between 1973 and 1998 in addition to mortality data covering the Metropolitan Detroit area obtained from the Michigan Department of Community Health. Data for Caucasian and African -American men were analyzed. The use of androgen-deprivation therapy, which evolved during the study period, was evaluated in conjunction with mortality and incidence trend data for consideration of etiologic contributions. RESULTS. The incidence of prostate carcinoma, as noted previously in national data, increased sharply in 1988, peaking in 1992 in Southeast Michigan, whereas mortality rates began to decrease in approximately 1993, with a sustained decrease to the latest recorded data in 1998. These trends were identical in Caucasians and African Americans. A sharp increase in the use of androgen - deprivation therapy began in 1990. This use of androgen- deprivation therapy is high and sustained for patients with early-stage disease, increases for several years, and then diminishes for patients with regional disease. The use also diminished through the 1990s for patients with late-stage disease, paralleling the decrease in the incidence rate for late-stage disease. CONCLUSIONS. The pattern of androgen- deprivation therapy usage was consistent with that for hormonal monotherapy and adjuvant and neoadjuvant therapy. These findings suggest that androgen- deprivation therapy may contribute, along with advances in diagnostic techniques and curative therapy with radiation or surgery, toward decreasing prostate carcinoma mortality rates in Southeast Michigan. (C) 2001 American Cancer Society. C1 Josephine Ford Canc Ctr, Henry Ford Hlth Syst, Dept Urol, Detroit, MI 48202 USA. NCI, Organ Syst Branch, Ann Arbor, MI USA. Wayne State Univ, Epidemiol Sect, Barbara Ann Karmanos Canc Inst, Detroit Med Ctr, Detroit, MI USA. RP Demers, RY (reprint author), Josephine Ford Canc Ctr, Henry Ford Hlth Syst, Dept Urol, 1 Ford Pl,5C, Detroit, MI 48202 USA. NR 38 TC 31 Z9 32 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2001 VL 92 IS 9 BP 2309 EP 2317 DI 10.1002/1097-0142(20011101)92:9<2309::AID-CNCR1577>3.0.CO;2-8 PG 9 WC Oncology SC Oncology GA 485TR UT WOS:000171780500010 PM 11745285 ER PT J AU Tseng, JE Glisson, BS Khuri, FR Shin, DM Myers, JN El-Naggar, AK Roach, JS Ginsberg, LE Thall, PF Wang, XM Teddy, S Lawhorn, KN Zentgraf, RE Steinhaus, GD Pluda, JM Abbruzzese, JL Hong, WK Herbst, RS AF Tseng, JE Glisson, BS Khuri, FR Shin, DM Myers, JN El-Naggar, AK Roach, JS Ginsberg, LE Thall, PF Wang, XM Teddy, S Lawhorn, KN Zentgraf, RE Steinhaus, GD Pluda, JM Abbruzzese, JL Hong, WK Herbst, RS TI Phase II study of the antiangiogenesis agent thalidomide in recurrent or metastatic squamous cell carcinoma of the head and neck SO CANCER LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 19-23, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Soc Clin Oncol DE angiogenesis; thalidomide; squamous cell carcinoma of the head and neck; vascular endothelial growth factor; basic fibroblast growth factor ID FIBROBLAST-GROWTH-FACTOR; REFRACTORY MULTIPLE-MYELOMA; RNA HYBRIDIZATION TECHNIQUE; BREAST-CANCER PATIENTS; LUPUS-ERYTHEMATOSUS; CYTOKINE MODULATION; ANGIOGENIC FACTORS; BEHCETS SYNDROME; FACTOR RECEPTOR; TNF-ALPHA AB BACKGROUND. Thalidomide has been shown to have antiangiogenic effects in preclinical models as well as a significant antitumor effect in hematologic tumors such as multiple myeloma. The authors performed this Phase If study to determine the activity, toxicity profile, and antiangiogenic effect of thalidomide in patients with locoregionally recurrent or metastatic squamous cell carcinoma of the head and neck. METHODS. Twenty-one patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with single-agent thalidomide. All patients had received radiation therapy, and most had undergone surgery (95%) and/or chemotherapy (90%). Thalidomide was initiated at 200 mgdaily and increased to a target dose of 1000 mg daily. Patients continued treatment until disease progression, unacceptable toxicity, or death occurred, RESULTS. All 21 patients eventually developed progressive disease. Median time to progression was 50 days (95% confidence interval, 28-70), with median overall survival time of 194 days (95% lower confidence boundary, 151), similar to the progression and survival times reported for this patient group with other agents. Thalidomide was generally well tolerated, with few patients experiencing Grades 3 to 4 toxicities. Serum vascular endothelial growth factor and basic fibroblast growth factor levels increased in six of seven patients, for whom paired serum samples were available and all of whom had progressive disease. CONCLUSIONS. In this heavily pretreated population of patient,; with advanced squamous cell carcinoma of the head and neck, thalidomide does not appear to have single-agent antitumor activity. Further evaluation of the mechanism of action of thalidomide is indicated. Potentially, future evaluations of thalidomide may be performed in combination with other antiangiogenic or cytotoxic agents in patients with earlier stage disease or in patients with minimal residual disease. (C) 2001 American Cancer Society. C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. RP Herbst, RS (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Head & Neck Med Oncol, 1515 Holcombe Blvd,Box 432, Houston, TX 77030 USA. RI Ray, Dana/C-3470-2013; Shin, Dong Moon/G-9649-2013 FU NCI NIH HHS [UO1 CA-70172] NR 67 TC 43 Z9 45 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2001 VL 92 IS 9 BP 2364 EP 2373 DI 10.1002/1097-0142(20011101)92:9<2364::AID-CNCR1584>3.0.CO;2-P PG 10 WC Oncology SC Oncology GA 485TR UT WOS:000171780500017 PM 11745292 ER PT J AU Steenland, K Mannetje, A Boffetta, P Stayner, L Attfield, M Chen, JQ Dosemeci, M DeKlerk, N Hnizdo, E Koskela, R Checkoway, H AF Steenland, K Mannetje, A Boffetta, P Stayner, L Attfield, M Chen, JQ Dosemeci, M DeKlerk, N Hnizdo, E Koskela, R Checkoway, H TI Pooled exposure-response analyses and risk assessment for lung cancer in 10 cohorts of silica-exposed workers: an IARC multicentre study SO CANCER CAUSES & CONTROL LA English DT Article DE lung cancer; multicentre study; silica ID DIATOMACEOUS-EARTH INDUSTRY; AFRICAN GOLD MINERS; NESTED CASE-CONTROL; URANIUM MINERS; CRYSTALLINE SILICA; POTTERY WORKERS; DUST EXPOSURES; MORTALITY; MISCLASSIFICATION; ASSOCIATIONS AB Objectives: Silica is one of the most common occupational exposures worldwide. In 1997 the International Agency for Research on Cancer (IARC) classified inhaled crystalline silica as a human carcinogen (group 1), but acknowledged limitations in the epidemiologic data, including inconsistencies across studies and the lack of extensive exposure-response data. We have conducted a pooled exposure-response analysis of 10 silica-exposed cohorts to investigate lung cancer. Methods: The pooled cohort included 65,980 workers (44,160 miners, 21,820 nominees), and 1072 lung cancer deaths (663 miners, 409 nonminers). Follow-up has been extended for five of these cohorts beyond published data. Quantitative exposure estimates by job and calendar time were adopted, modified, or developed to permit common analyses by respirable silica (mg/m(3)) across cohorts. Results: The log of cumulative exposure, with a 15-year lag, was a strong predictor of lung cancer (p = 0.0001), with consistency across studies (test for heterogeneity, p = 0.34). Results for the log of cumulative exposure were consistent between underground mines and other facilities. Categorical analyses by quintile of cumulative exposure resulted in a monotonic trend with odds ratios of 1.0, 1.0, 1.3, 1.5, 1.6. Analyses using a spline curve also showed a monotonic increase in risk with increasing exposure. The estimated excess lifetime risk (through age 75) of lung cancer for a worker exposed from age 20 to 65 at 0.1 mg/m(3) respirable crystalline silica (the permissible level in many countries) was 1.1-1.7%, above background risks of 3-6%. Conclusions: Our results support the decision by the IARC to classify inhaled silica in occupational settings as a carcinogen, and suggest that the current exposure limits in many countries may be inadequate. These data represent the first quantitative exposure-response analysis and risk assessment for silica using data from multiple studies. C1 NIOSH, Cincinnati, OH 45226 USA. Int Agcy Res Canc, F-69372 Lyon, France. NIOSH, Morgantown, WV USA. Tongji Med Univ, Wuhan, Peoples R China. Natl Canc Inst, Washington, DC USA. Univ Western Australia, Perth, WA 6009, Australia. Finnish Inst Occupat Hlth, Helsinki, Finland. Univ Washington, Seattle, WA 98195 USA. RP Steenland, K (reprint author), Dept Hlth & Human Serv, Robert A Taft Labs, 4676 Columbia Pkwy, Cincinnati, OH 45226 USA. RI de Klerk, Nicholas/D-8388-2016 OI de Klerk, Nicholas/0000-0001-9223-0767 NR 57 TC 134 Z9 143 U1 1 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2001 VL 12 IS 9 BP 773 EP 784 DI 10.1023/A:1012214102061 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 479HB UT WOS:000171398000001 PM 11714104 ER PT J AU Hirvonen, T Virtamo, J Korhonen, P Albanes, D Pietinen, P AF Hirvonen, T Virtamo, J Korhonen, P Albanes, D Pietinen, P TI Flavonol and flavone intake and the risk of cancer in male smokers (Finland) SO CANCER CAUSES & CONTROL LA English DT Article DE cohort studies; flavonoids; neoplasms ID POTENTIALLY ANTICARCINOGENIC FLAVONOIDS; OCCURRING PLANT PHENOLS; DIETARY FLAVONOIDS; LUNG-CANCER; PROSPECTIVE COHORT; TEA CONSUMPTION; HEART-DISEASE; BLACK TEA; QUERCETIN; INHIBITION AB Objective: To study the associations between the intake of flavonols and flavones and the risk of cancer. Methods: The study cohort consisted of 27,110 male smokers, aged 50-69 years, without history of cancer. They were participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in Finland. The men completed a validated dietary questionnaire at baseline. Incident cases of cancers were identified through national registers. During an average 6.1-year follow-up, 791 lung cancers, 226 prostate cancers, 156 urothelial cancers, 133 colorectal cancers, 111 stomach cancers, and 92 renal cell cancers were diagnosed. Results: Intake of flavonols and flavones was inversely associated with the risk of lung cancer; multivariate relative risk in the highest vs. the lowest quartile 0.56, 95% confidence interval 0.45-0.69, p for trend 0.0001. The risk was similar in all histological types of lung cancer. No association was found between flavonol and flavone intake and the risk of other cancers. Conclusions: Intake of flavonols and flavones seemed to be inversely associated with the risk of lung cancer, but not with that of other cancers. C1 Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, FIN-0300 Helsinki, Finland. NCI, Div Clin Sci, Bethesda, MD USA. RP Hirvonen, T (reprint author), Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Mannerheimintie 166, FIN-0300 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-SC-45165] NR 49 TC 95 Z9 99 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2001 VL 12 IS 9 BP 789 EP 796 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 479HB UT WOS:000171398000003 PM 11714106 ER PT J AU Abnet, CC Borkowf, CB Qiao, YL Albert, PS Wang, E Merrill, AH Mark, SD Dong, ZW Taylor, PR Dawsey, SM AF Abnet, CC Borkowf, CB Qiao, YL Albert, PS Wang, E Merrill, AH Mark, SD Dong, ZW Taylor, PR Dawsey, SM TI Sphingolipids as biomarkers of fumonisin exposure and risk of esophageal squamous cell carcinoma in China SO CANCER CAUSES & CONTROL LA English DT Article DE esophageal cancer; fumonisin; sphinganine; sphingolipids; sphingosine ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; REPUBLIC-OF-CHINA; FUSARIUM-MONILIFORME; CANCER INCIDENCE; SPHINGOSINE; MYCOTOXINS; LINXIAN; SPHINGANINE; CORN AB Objective: Ecologic studies of esophageal squamous cell carcinoma (ESCC) have reported an association with consumption of maize contaminated with Fusarium verticillioides, which produce fungal toxins referred to as fumonisins. Fumonisins disrupt sphingolipid metabolism and serum sphingolipids have been proposed as biomarkers of fumonisin exposure. We conducted a prospective nested case-control study to examine the relationship between serum sphingolipids and ESCC incidence. Methods: Cases and controls were selected from a large prospective trial conducted in Linxian, People's Republic of China. Ninety-eight ESCC cases were randomly selected from the 639 incident ESCC ascertained during the initial 5.25 years of follow-up; 185 controls were also randomly selected based on the distribution of cases among six age and sex strata. Concentrations of sphinganine and sphingosine were determined by high-performance liquid chromatography in serum collected at the study baseline. Results: No significant associations were found between serum sphingosine, sphinganine, or the sphinganine/sphingosine ratio and ESCC incidence in conditional and unconditional logistic regression models with adjustment for age, sex, tobacco use, and alcohol use. Conclusion: Our study is the first prospective study to assess the relationship between sphingolipid levels, as biomarkers of fumonisin exposure, and cancer incidence. We found no significant association between sphingolipid levels and risk of ESCC. C1 NCI, Ctr Canc Res, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing, Peoples R China. NCI, Div Canc Treatment & Diag, Bethesda, MD USA. Emory Univ, Rollins Res Ctr, Dept Biochem, Atlanta, GA 30322 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Abnet, CC (reprint author), NCI, Ctr Canc Res, Canc Prevent Studies Branch, 6006 Execut Blvd,Room 321, Bethesda, MD 20892 USA. RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 38 TC 43 Z9 45 U1 1 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2001 VL 12 IS 9 BP 821 EP 828 DI 10.1023/A:1012228000014 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 479HB UT WOS:000171398000007 PM 11714110 ER PT J AU Hatch, EE Herbst, AL Hoover, RN Noller, KL Adam, E Kaufman, RH Palmer, JR Titus-Ernstoff, L Hyer, M Hartge, P Robboy, SJ AF Hatch, EE Herbst, AL Hoover, RN Noller, KL Adam, E Kaufman, RH Palmer, JR Titus-Ernstoff, L Hyer, M Hartge, P Robboy, SJ TI Incidence of squamous neoplasia of the cervix and vagina in women exposed prenatally to diethylstilbestrol (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE cervix; cohort study; diethylstilbestrol; squamous neoplasia; vagina ID YOUNG-WOMEN; IN-UTERO; DESAD PROJECT; NATIONAL-COOPERATIVE-DIETHYLSTILBESTROL-ADENOSIS-(DESAD)-PROJECT; INUTERO; CANCER AB Objectives: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the effect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. Methods: A cohort comprising 3899 DES-exposed and 1374 unexposed daughters was followed for 13 years (1982-1995) for pathology-confirmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% confidence intervals (95% CI), adjusting for age, calendar year, and other covariates. Results: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2-3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little effect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4-5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. Conclusions: The findings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Massachusetts, Med Ctr, Dept Obstet & Gynecol, Worcester, MA USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Boston Univ, Sch Publ Hlth, Slone Epidemiol Unit, Boston, MA USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. Informat Management Serv Inc, Rockville, MD USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. RP Hatch, EE (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 715 Albany St T3E, Boston, MA 02118 USA. NR 21 TC 40 Z9 42 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2001 VL 12 IS 9 BP 837 EP 845 DI 10.1023/A:1012229112696 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 479HB UT WOS:000171398000009 PM 11714112 ER PT J AU Abnet, CC Qiao, YL Mark, SD Dong, ZW Taylor, PR Dawsey, SM AF Abnet, CC Qiao, YL Mark, SD Dong, ZW Taylor, PR Dawsey, SM TI Prospective study of tooth loss and incident esophageal and gastric cancers in China SO CANCER CAUSES & CONTROL LA English DT Article DE esophageal cancer; gastric cancer; nitrosamines; tooth loss ID REPUBLIC-OF-CHINA; N-NITROSO COMPOUNDS; ENDOGENOUS FORMATION; RISK-FACTORS; LINXIAN; MORTALITY; DIET AB Objective: To determine the association between tooth loss and the risk of developing esophageal squamous cell carcinoma, gastric cardia adenocarcinoma, or gastric non-cardia adenocarcinoma in a prospective study. Methods: Cox proportional hazards regression was used to examine these associations in a 28,868-person cohort followed prospectively for 5.25 years. The baseline questionnaire included questions regarding tooth loss, and individuals reporting lost teeth had their teeth counted by study personnel. The analytic cohort included 620 esophagus, 431 gastric cardia, and 102 gastric non-cardia cancer cases. Results: Tooth loss was associated with a significantly elevated risk of developing all three cancers. When examined as median splits, tooth loss was associated with a relative risk (RR) (95% confidence interval, CI) of 1.3 (1.1-1.6) in the esophagus, 1.3 (1.0-1.6) in the gastric cardia, and 1.8 (1.1-3.0) in the gastric non-cardia. Further analysis demonstrated that this increased risk was most strongly associated with the loss of the first few teeth and was primarily confined to the younger members of our cohort. Conclusions: In this cohort tooth loss increased the risk of developing upper gastrointestinal cancer. We hypothesize that this may be related to alterations in oral bacterial flora and subsequent increases in the in-vivo production of carcinogens such as nitrosamines. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Dept Epidemiol, Beijing 100021, Peoples R China. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Abnet, CC (reprint author), NCI, Canc Prevent Studies Branch, Div Clin Sci, 6116 Execut Blvd,Room 705, Bethesda, MD 20892 USA. RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 19 TC 79 Z9 82 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2001 VL 12 IS 9 BP 847 EP 854 DI 10.1023/A:1012290009545 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 479HB UT WOS:000171398000010 PM 11714113 ER PT J AU Stecklair, KP Hamburger, DR Egorin, MJ Parise, RA Covey, JM Eiseman, JL AF Stecklair, KP Hamburger, DR Egorin, MJ Parise, RA Covey, JM Eiseman, JL TI Pharmacokinetics and tissue distribution of halofuginone (NSC 713205) in CD2F1 mice and Fischer 344 rats SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE halofuginone; pharmacokinetics; collagen type I; matrix metalloproteinase ID ANTICANCER DRUG TARGETS; VERSUS-HOST DISEASE; I SYNTHESIS; INTIMAL HYPERPLASIA; CELL-PROLIFERATION; INHIBITOR; ANGIOGENESIS; DISCOVERY; PROGRESSION; METASTASIS AB Purpose: Halofuginone (HF) inhibits synthesis of collagen type I and matrix metalloproteinase-2 and is being considered for clinical evaluation as an antineoplastic agent. Pharmacokinetic studies were performed in rodents to define the plasma pharmacokinetics, tissue distribution, and urinary excretion of HF after i.v. delivery and the bioavailability of HF after Lp. and oral delivery. Materials and methods: Studies were performed in CD2F1 mice and Fischer 344 rats. In preliminary toxicity studies in mice single HF i.v. bolus doses between 1.0 and 5.0 mg/kg were used. Pharmacokinetic studies were conducted in mice after administration of 1.5 mg/kg HF. In preliminary toxicity studies in male rats HF i.v. bolus doses between 0.75 and 4.5 mg/kg were used. In pharmacokinetic studies in rats an HF dose of 3.0 mg/kg was used. Compartmental and non-compartmental analyses were applied to the plasma concentration versus time data. Plasma, red blood cells, various organs, and urine were collected for analysis. Results: HF doses greater than or equal to1.5 mg/kg proved excessively toxic to mice. In mice, Lv. bolus delivery of 1.5 mg/kg HF produced "peak" plasma HF concentrations between 313 and 386 ng/ml, and an AUC of 19,874 ng/ml-min, which corresponded to a total body clearance (CLtb) of 75 ml/min per kg. Plasma HF concentration versus time data were best fit by a two-compartment open linear model. The bioavailability of HF after i.p. and oral delivery to mice was 100% and 0%, respectively. After i.v. bolus delivery to mice, HF distributed rapidly to all tissues, except brain. HF persisted in lung, liver, kidney, spleen, and skeletal muscle longer than in plasma. In the oral study, HF was undetectable in plasma and red blood cells, but was easily detectable in kidney, liver, and lung, and persisted in those tissues for 48 h. Urinary excretion of HF accounted for 7-11 % of the administered dose within the first 72 h after i.v. dosing and 15-16% and 16% of the administered dose within 24 and 48 h, respectively, after oral dosing. There were no observed metabolites of HF in mouse plasma or tissues. In rats, i.v. bolus delivery of 3.0 mg/kg produced a "peak" plasma HF concentration of 348 ng/ml, and an AUC of 43,946 ng/ml-min, which corresponded to a CLtb of 68 ml/min per kg. Plasma HF concentration versus time data were best fit by a two-compartment open linear model. After i.v. bolus delivery to rats, HF distributed rapidly to all tissues, with low concentrations detectable in brain and testes. HF was detectable in some tissues for up to 48 h. HF could be detected in rat plasma after a 3 mg/kg oral dose. Peak HF concentration (34 ng/ml) occurred at 90 min, but HF concentrations were less than the lower limit of quantitation (LLQ) by 420 min. Urinary excretion of HF accounted for 8-11 % of the administered dose within the first 48 h after i.v. dosing. No HF metabolites were detected in plasma, tissue, or urine. Conclusions: HF was rapidly and widely distributed to rodent tissues and was not converted to detectable metabolites. In mice, HF was 100% bioavailable when given i.p. but could not be detected in plasma after oral administration. suggesting limited oral bioavailability. However. substantial concentrations were present In liver. kidney. and lungs. HF was present in rat plasma after an oral dose. but the time course and low concentrations achieved precluded reliable estimation of bioavailability. These data may assist in designing and interpreting additional preclinical and clinical studies of HF. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Egorin, MJ (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, E1040 Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [N01-CM07106, 2P30 CA47904] NR 39 TC 9 Z9 10 U1 1 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2001 VL 48 IS 5 BP 375 EP 382 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 498BF UT WOS:000172489400006 PM 11761455 ER PT J AU Hildesheim, A Dosemeci, M Chan, CC Chen, CJ Cheng, YJ Hsu, MM Chen, IH Mittl, BF Sun, B Levine, PH Chen, JY Brinton, LA Yang, CS AF Hildesheim, A Dosemeci, M Chan, CC Chen, CJ Cheng, YJ Hsu, MM Chen, IH Mittl, BF Sun, B Levine, PH Chen, JY Brinton, LA Yang, CS TI Occupational exposure to wood, formaldehyde, and solvents and risk of nasopharyngeal carcinoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NONRADIOACTIVE OLIGONUCLEOTIDE PROBES; POLYMERASE CHAIN-REACTION; SQUAMOUS-CELL CANCERS; SINONASAL CANCER; NASAL CAVITY; WORKERS; MORTALITY; VIRUS; POLYMORPHISM; ANTIBODIES AB Our objective was to evaluate the link between occupational exposures to wood dust, formaldehyde, and solvents and the development of nasopharyngeal carcinoma (NPC). A case-control study was conducted among 375 newly diagnosed cases of NPC in Taipei, Taiwan, and 325 community controls matched to cases on sex, age, and geographical residence (99 and 87% response rates, respectively). Most cases (> 90%) were diagnosed with WHO Types 2 or 3 (nonkeratinizing and undifferentiated carcinomas), whereas the remaining cases were diagnosed with WHO Type I (squamous cell carcinomas). A complete occupational history was obtained via a personal interview and blindly assessed by an industrial hygienist for intensity and probability of exposure to wood dust, formaldehyde, and solvents. Information on socio-demographic characteristics, cigarette smoking, dietary consumption of nitrosamines, and other potential confounding factors was obtained via a personal interview. Blood specimens were tested for human leukocyte antigen class I/II genotypes, polymorphisms in cytochrome P450 2E1 genotype, and various anti-EBV antibodies known to be associated with NPC. Analysis was performed using logistic regression; relative risk (RR) estimates and 95% confidence intervals (CI) were calculated. Individuals exposed to wood dust had an adjusted RR of 1.7 (95% Cl = 1.0-3.0). Those exposed to wood dust for > 10 years had an adjusted RR of 2.4 (95% CI = 1-1-5-0; p(trend) = 0.02). Risk was strongest for those first exposed before the age of 25 years and those seropositive to EBV. Individuals exposed to formaldehyde were at a more modest and nonsignificant increased risk of NPC (RR = 1.4; 95% CI = 0.93-2.2). Those exposed to formaldehyde for > 10 years had an adjusted RR of 1.6 (95% Cl = 0.91-2.9). The association between formaldehyde and NPC was stronger in analyses restricted to EBV seropositive individuals (RR = 2.7; 95% CI = 1.2-5.9). However, no dose response was observed with increasing duration or cumulative use. No association was observed between solvent exposure and NPC (RR = 1.2; 95% CI = 0.86-1.7). Occupational exposure to wood dust is likely to be involved in the development of NPC, a finding that is consistent with the known link between wood exposure and nasal adenocarcinomas. Formaldehyde exposure is less clearly linked to NPC, whereas exposure to solvents is unlikely to be involved in NPC pathogenesis. C1 NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Bethesda, MD 20892 USA. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Occupat Med & Ind Hyg, Taipei 10764, Taiwan. Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol, Taipei 10764, Taiwan. Natl Taiwan Univ, Dept Otolaryngol, Taipei 10764, Taiwan. Natl Taiwan Univ, Coll Med, Dept Microbiol, Taipei, Taiwan. MacKay Mem Hosp, Dept Otolaryngol, Taipei, Taiwan. Westat Inc, Rockville, MD USA. RP Hildesheim, A (reprint author), NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, 6120 Execut Blvd,Room 7062, Bethesda, MD 20892 USA. RI Chen, Chien-Jen/C-6976-2008; Brinton, Louise/G-7486-2015; OI Brinton, Louise/0000-0003-3853-8562; CHAN, CHANG-CHUAN/0000-0002-7518-5236 NR 45 TC 78 Z9 84 U1 2 U2 13 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2001 VL 10 IS 11 BP 1145 EP 1153 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 492DX UT WOS:000172154100006 PM 11700262 ER PT J AU Stellman, SD Takezaki, T Wang, L Chen, Y Citron, ML Djordjevic, MV Harlap, S Muscat, JE Neugut, AI Wynder, EL Ogawa, H Tajima, K Aoki, K AF Stellman, SD Takezaki, T Wang, L Chen, Y Citron, ML Djordjevic, MV Harlap, S Muscat, JE Neugut, AI Wynder, EL Ogawa, H Tajima, K Aoki, K TI Smoking and lung cancer risk in American and Japanese men: An international case-control study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EX-SMOKERS; COMPARATIVE EPIDEMIOLOGY; CIGARETTE-SMOKING; UNITED-STATES; AGE; SUSCEPTIBILITY; MORTALITY; FREQUENCY; PATTERNS; CYP1A1 AB Rates of lung cancer in American men have greatly exceeded those in Japanese men for several decades despite the higher smoking prevalence in Japanese men. It is not known whether the relative risk of lung cancer associated with cigarette smoking is lower in Japanese men than American men and whether these risks vary by the amount and duration of smoking. To estimate smoking-specific relative risks for lung cancer in men, a multicentric case-control study was carried out in New York City, Washington, DC, and Nagoya, Japan from 1992 to 1998. A total of 371 cases and 373 age-matched controls were interviewed in United States hospitals and 410 cases and 252 hospital controls in Japanese hospitals; 411 Japanese age-matched healthy controls were also randomly selected from electoral rolls. The odds ratio (OR) for lung cancer in current United States smokers relative to nonsmokers was 40.4 [95% confidence interval (CI) = 21.8-79.6], which was > 10 times higher than the OR of 3.5 for current smokers in Japanese relative to hospital controls (95% CI = 1.6-7.5) and six times higher than in Japanese relative to community controls (OR = 6.3; 95% CI = 3.7-10.9). There were no substantial differences in the mean number of years of smoking or average daily number of cigarettes smoked between United States and Japanese cases or between United States and Japanese controls, but American cases began smoking on average 2.5 years earlier than Japanese cases. The risk of lung cancer associated with cigarette smoking was substantially higher in United States than in Japanese males, consistent with population-based statistics on smoking prevalence and lung cancer incidence. Possible explanations for this difference in risk include a more toxic cigarette formulation of American manufactured cigarettes as evidenced by higher concentrations of tobacco-specific nitrosamines in both tobacco and mainstream smoke, the much wider use of activated charcoal in the filters of Japanese than in American cigarettes, as well as documented differences in genetic susceptibility and lifestyle factors other than smoking. C1 Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. Amer Hlth Fdn, Div Epidemiol, Valhalla, NY 10595 USA. Aichi Canc Res Inst, Div Epidemiol, Nagoya, Aichi, Japan. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. ProHlth Inc, New Hyde Park, NY 11042 USA. NCI, Tobacco Control Res Branch, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. NYU, Sch Med, New York, NY 10016 USA. Aichi Mizuho Coll, Dept Human Sci, Toyota, Japan. Aichi Canc Ctr, Nagoya, Aichi 464, Japan. RP Stellman, SD (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 630 W 168th St PH-18, New York, NY 10032 USA. FU NCI NIH HHS [CA-17613, CA-32617, CA-68384] NR 46 TC 82 Z9 84 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2001 VL 10 IS 11 BP 1193 EP 1199 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 492DX UT WOS:000172154100012 PM 11700268 ER PT J AU London, SJ Xia, J Lehman, TA Yang, JH Granada, E Chunhong, L Dubeau, L Li, T David-Beabes, GL Li, Y AF London, SJ Xia, J Lehman, TA Yang, JH Granada, E Chunhong, L Dubeau, L Li, T David-Beabes, GL Li, Y TI Collection of buccal cell DNA in seventh-grade children using water and a toothbrush SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYMERASE CHAIN-REACTION; GENOMIC DNA; GENE; POPULATIONS; PCR; POLYMORPHISMS; MUTATIONS; SAMPLES; REGION; SWABS AB We developed a simple and effective method for collecting a large quantity of buccal cell DNA in school-based studies of seventh-grade and older children. Seventh-grade students at schools in Wuhan, China brushed each buccal surface with a soft toothbrush and then rinsed with 10 ml of water. We added 5 ml of 99% ethanol to preserve the sample. Among 1563 samples transported at room temperature over 1 week and then stored for 13-14 months at -70 degreesC before extraction, using a modified Gentra Puregene protocol, the median total DNA yield was 108 mug, range of 14 to 416 mug. We assayed every 20th sample (n = 77) for NAT2 by the PCR, and all samples gave a 1093-bp product. From the 1563 samples, we obtained a result for single nucleotide polymorphisms in the interleukin-13 gene (at +2044) by RFLP-PCR on 98.8% and in the promoter of the myeloperoxidase gene (at -463) by real-time PCR on 99.7%. A water-rinse method, that we used among 12th-grade students in Southern California, gave a lower total DNA yield than the toothbrush rinse (median of 17 mug) and a slightly reduced ability to generate a PCR product. However, 26 of 27 water-rinse samples gave a result for two genes, albumin and CYP1A1, using real-time PCR methods. We did not quantify human, versus bacterial, DNA in our samples. However, given the amounts of total DNA required for genotyping, a sample with the median yield of 108 mug should suffice for similar to 2160 genotypes by RFLP-PCR methods or five times as many by real-time PCR. We recommend the toothbrush-rinse method, combined with a modified Gentra Puregene DNA extraction protocol, for large-scale, in-person collections of buccal cell DNA in children. The method requires only inexpensive, readily available materials and produces a large quantity of high-quality DNA for PCR analyses. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. Wuhan Publ Hlth & AntiEpidem Stn, Wuhan 430022, Peoples R China. BioServe Biotechnol Ltd, Laurel, MD 20707 USA. Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP London, SJ (reprint author), NIEHS, Epidemiol Branch, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. OI London, Stephanie/0000-0003-4911-5290 FU NIEHS NIH HHS [5P30 ES07048, Z01 ES-49019] NR 24 TC 23 Z9 25 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2001 VL 10 IS 11 BP 1227 EP 1230 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 492DX UT WOS:000172154100018 PM 11700274 ER PT J AU Kawakami, K Husain, SR Bright, RK Puri, RK AF Kawakami, K Husain, SR Bright, RK Puri, RK TI Gene transfer of interleukin 13 receptor alpha 2 chain dramatically enhances the antitumor effect of IL-13 receptor-targeted cytotoxin in human prostate cancer xenografts SO CANCER GENE THERAPY LA English DT Article DE interleukin-13 receptor; cytotoxin therapy; gene therapy; prostate cancer; sensitization; Pseudomonas exotoxin ID GROWTH-FACTOR RECEPTORS; CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; (IL)-13 BINDING; SARCOMA-CELLS; CLONING; COMPONENT; IMMUNOTOXINS AB IL-13R alpha2 chain, the primary interleukin-13 (IL-13) binding protein, plays an important role in IL-13 binding and internalization. Based on these findings, in our previous study we transiently transfected four cancer cell lines that do not express IL-13R alpha2 chain and demonstrated that these cells acquired increased sensitivity to IL-13 receptor-targeted recombinant cytotoxin, IL13-PE38QQR, which is composed of IL-13 and a mutated form of a Pseudomonas exotoxin. Although some prostate cancer cell lines express functional IL-13R, they are not highly sensitive to IL-13 cytotoxin. Here we investigated whether human prostate cancer and normal prostate epithelial cell lines express IL-13R alpha2 chain and whether they can be sensitized to the cytotoxic effect of IL-13 cytotoxin after transient or stable gene transfer of IL-13R alpha2 chain. Gene transfer of IL-13R alpha2 chain improved binding activity of IL-13 and sensitivity to IL-13 cytotoxin in vitro. In vivo experiments demonstrated that gene transfer of IL-13R alpha2 chain dramatically enhanced the antitumor activity of IL-13 cytotoxin in human prostate cancer xenograft models. These results suggest that IL-13R-targeted cytotoxin therapy of prostate cancer may be dramatically enhanced by gene transfer of IL-13R alpha2 chain and this strategy, the combination of gene therapy and cytotoxin therapy, may be utilized in the treatment of localized prostate cancer. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Chiles Res Inst, Franz Canc Res Ctr, Portland, OR 97213 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 36 TC 29 Z9 30 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV PY 2001 VL 8 IS 11 BP 861 EP 868 DI 10.1038/sj.cgt.7700373 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 494GA UT WOS:000172272300004 PM 11773976 ER PT J AU Harford, JB AF Harford, JB TI The new era of molecular targets for cancer therapy SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV PY 2001 VL 8 IS 11 MA O17 BP 913 EP 913 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 494GA UT WOS:000172272300024 ER PT J AU Espinoza, LA Neto, JB Popescu, NC Casartelli, C AF Espinoza, LA Neto, JB Popescu, NC Casartelli, C TI Deletion 5p11 accompanied by multiple numerical changes in testicular lymphoma SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID GERM-CELL TUMORS; NON-HODGKINS-LYMPHOMA AB We describe a case of testicular B cell lymphoma with deletion of chromosome 5, del(5)(p11), as a sole structural abnormality. Histopathological diagnosis of the tumor was a high-grade lymphoma of the diffuse type containing cells positive for B cell specific antigen (CD20) and negative for the leukocyte common antigen (CD45). Deletion 5p may define the region of a tumor suppressor gene that could be associated with tumor progression and invasiveness and may serve as an indicator of poor prognosis in testicular lymphomas. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, Ribeirao Preto, SP, Brazil. Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Patol, Ribeirao Preto, SP, Brazil. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Espinoza, LA (reprint author), Georgetown Univ, Sch Med, Dept Biochem & Mol Biol, Basic Sci Bldg R345,3900 Reservoir Rd NW, Washington, DC 20007 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD NOV PY 2001 VL 131 IS 1 BP 79 EP 81 DI 10.1016/S0165-4608(01)00495-2 PG 3 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 500KR UT WOS:000172626800014 PM 11734324 ER PT J AU Bergmann-Leitner, ES Abrams, SI AF Bergmann-Leitner, ES Abrams, SI TI Treatment of human colon carcinoma cell lines with anti-neoplastic agents enhances their lytic sensitivity to antigen-specific CD8(+) cytotoxic T lymphocytes SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE human; CTL; apoptosis; tumor immunity; caspases ID FAS-MEDIATED CYTOTOXICITY; CANCER-CELLS; GAMMA-INTERFERON; APOPTOSIS; 5-FLUOROURACIL; EXPRESSION; THERAPY; CTL; INDUCTION; DRUGS AB Certain anti-neoplastic agents at subtoxic doses may exert immunomodulatory effects, which alter the expression of specific tumor cell surface molecules. We reasoned that potential increases in tumor cell surface markers. such as those important for facilitating effector-target contact, as well as triggering cell death pathways, might then improve antigen (Ag-specific T-cell-mediated tumor cytolysis. Here, in a human colon carcinoma cell model in vitro, we examined whether the anti-neoplastic agents 5-fluorouracil (5-FU), CPT-11 or cisplatin (CDDP) could upregulate the expression of specific tumor cell surface markers, which may then enhance productive lytic interactions between CD8(+) CTL and Ag-bearing tumor cells. Based on our earlier studies, IFN-gamma treatment was included as a control for sensitization to CTL-mediated lysis. Pretreatment of the SW480 primary colon carcinoma cell line with IFN-gamma, 5-FU, CPT-11 or CDDP enhanced ICAM-1 and Fas expression, resulting in Ag-specific CTL-mediated lysis involving Fas-dependent and -independent mechanisms. In contrast, pretreatment of the SW620 metastatic isolate, derived from the same patient, with IFN-gamma, CPT-11 or CDDP, but not 5-FU. enhanced ICAM-1 expression, resulting in Ag-specific CTL-mediated lysis via Fas-independent mechanisms only. Flow cytometric-based assays were then developed to measure the effects of drug treatment on caspase signaling and apoptosis incurred by tumor targets after interaction with CTL. We found that the lytic enhancement caused by drug treatment of SW480 or SW620 targets was accompanied by an increase in caspase-3-like protease activity. A peptide-based caspase inhibitor abrogated CTL-mediated apoptosis., suggesting that "chemomodulation" involved regulation of the caspase pathway. These results revealed for the first time an important role for components of the caspase pathway, such as caspase-3-like proteases, in the sensitization of human colon carcinoma cells by anti-neoplastic agents to Ag-specific CTL. Thus, certain anti-neoplastic agents may display unique immunoregulatory properties that facilitate human colon carcinoma death by engaging the lytic capacity of Ag-specific CTL, which may have implications for chemoimmunotherapy strategies. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Abrams, SI (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bldg 10,Room 5B46,10 Ctr Dr, Bethesda, MD 20892 USA. RI Bergmann-Leitner, Elke/B-3548-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956 NR 33 TC 59 Z9 60 U1 2 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD NOV PY 2001 VL 50 IS 9 BP 445 EP 455 DI 10.1007/s002620100229 PG 11 WC Oncology; Immunology SC Oncology; Immunology GA 498BE UT WOS:000172489300001 PM 11761438 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI Cellular therapy: An introduction SO CANCER JOURNAL LA English DT Editorial Material ID LYMPHOCYTES AB Cellular therapy is defined as the transfer, to the intact host, of living cells with the intent of introducing new host functions or correcting defective functions. The appeal and the promise of cellular therapy derive from the ability to manipulate, ex vivo, cellular and molecular biologic pathways in a way that is not possible in the intact organism. C1 NCI, Surg Branch, COP, DCT,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, COP, DCT,Ctr Canc Res,NIH, Bldg 10 Room 2B42,10 Ctr Dr MSC 1502, Bethesda, MD 20892 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD NOV-DEC PY 2001 VL 7 SU 2 BP S51 EP S52 PG 2 WC Oncology SC Oncology GA 503ZJ UT WOS:000172831300001 PM 11777264 ER PT J AU Kershaw, MH Hsu, C Mondesire, W Parker, LL Wang, G Overwijk, WW Lapointe, R Yang, JC Wang, RF Restifo, NP Hwu, P AF Kershaw, MH Hsu, C Mondesire, W Parker, LL Wang, G Overwijk, WW Lapointe, R Yang, JC Wang, RF Restifo, NP Hwu, P TI Immunization against endogenous retroviral tumor-associated antigens SO CANCER RESEARCH LA English DT Article ID DENDRITIC CELLS; METASTATIC MELANOMA; ANTITUMOR IMMUNITY; T-CELLS; PEPTIDE; GENE; EXPRESSION; VIRUS; PROTEIN; CANCER AB Endogenous retroviral gene products have been found in some human tumors, and therefore, may serve as antigens for immunotherapy approaches. The murine colorectal carcinoma CT26 and melanoma B16 have recently been found to express the endogenous retroviral gene products gp70 and p15E, respectively, that can serve as antigens recognized by T cells. To date, though, there has been no demonstration of tumor treatment using an endogenous retroviral protein. In this study, we demonstrate that mice immunized with recombinant vaccinia encoding the gp70 H2-L-d-restricted minimal determinant were protected from CT26 tumor challenge. Splenocytes from mice immunized with vaccinia gp70 specifically secreted IFN-gamma in response to gp70 peptide-pulsed stimulators. Although this strategy could protect against subsequent tumor challenge, it was ineffective against established tumors. Therefore, to investigate the treatment of established CT26 or B16 lung metastases, mice were treated with cultured dendritic cells (DCs) pulsed with gp70 or p15E peptide. Significant inhibition of established lung metastases required immunization with peptide-pulsed DCs pretreated with CD40 ligand that has been demonstrated to increase the T-cell stimulatory activity of DCs. The ability to immunize against endogenous retroviral tumor antigens may have relevance in the induction of antitumor immunity for some human cancers. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20814 USA. Baylor Coll Med, Dept Immunol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. RP Hwu, P (reprint author), NCI, Ctr Canc Res, NIH, Bldg 10,Room 2B-42,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 40 TC 34 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2001 VL 61 IS 21 BP 7920 EP 7924 PG 5 WC Oncology SC Oncology GA 489VQ UT WOS:000172013500034 PM 11691813 ER PT J AU Yuan, RQ Fan, S Achary, M Stewart, DM Goldberg, ID Rosen, EM AF Yuan, RQ Fan, S Achary, M Stewart, DM Goldberg, ID Rosen, EM TI Altered gene expression pattern in cultured human breast cancer cells treated with hepatocyte growth factor/scatter factor in the setting of DNA damage SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR; FACTOR PROTECTS; APOPTOSIS; DEATH; PHOSPHORYLATION; KINASE; REPAIR; POLYCYSTIN-1; GLIOBLASTOMA; REGULATOR AB The cytokine hepatocyte growth factor/scatter factor (HGF/SF) protects epithelial and cancer cells against DNA-damaging agents via a pathway involving signaling from c-Met --> phosphatidylinositol-3-kinase --> c-Akt. However, the downstream alterations in gene expression resulting from this pathway have not been established. On the basis of cDNA microarray and semiquantitative RT-PCR assays, we found that MDA-MB-453 human breast cancer cells preincubated with HGF/SF and then exposed to Adriamycin (ADR), a DNA topoisomerase II inhibitor, exhibit an altered pattern of gene expression, as compared with cells treated with ADR only. [HGF/SF+ADR]-treated cells showed altered expression of genes involved in the DNA damage response, cell cycle regulation, signal transduction, metabolism, and development. Some of these alterations suggest mechanisms by which HGF/SF may exert its protective activity, e.g., up-regulation of polycystic kidney disease-1 (a survival-promoting component of cadherin-catenin complexes), downregulation of 51C (an inositol polyphosphate-5-phosphatase), and downregulation of TOPBP1 (a topoisomerase IIB binding protein). We showed that enforced expression of the cdc42-interacting protein CIP4, a cytoskeleton-associated protein for which expression was decreased in [HGF/SF+ADR]-treated cells, inhibited HGF/SF-mediated protection against ADR. The cDNA microarray approach may open up new avenues for investigation of the DNA damage response and its regulation by HGF/SF. C1 Long Isl Jewish Med Ctr, Albert Einstein Coll Med, Dept Radiat Oncol, New Hyde Pk, NY 11040 USA. Albert Einstein Coll Med, Dept Radiat Oncol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Rosen, EM (reprint author), Long Isl Jewish Med Ctr, Albert Einstein Coll Med, Dept Radiat Oncol, Long Isl Campus,270-05 76th Ave, New Hyde Pk, NY 11040 USA. FU NIEHS NIH HHS [R01-ES09169]; PHS HHS [R01-82599, R01-80000] NR 33 TC 32 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2001 VL 61 IS 21 BP 8022 EP 8031 PG 10 WC Oncology SC Oncology GA 489VQ UT WOS:000172013500049 PM 11691828 ER PT J AU Kelavkar, UP Nixon, JB Cohen, C Dillehay, D Eling, TE Badr, KF AF Kelavkar, UP Nixon, JB Cohen, C Dillehay, D Eling, TE Badr, KF TI Overexpression of 15-lipoxygenase-1 in PC-3 human prostate cancer cells increases tumorigenesis SO CARCINOGENESIS LA English DT Article ID ENDOTHELIAL-CELL; LINOLEIC-ACID; 12(S)-HYDROXYEICOSATETRAENOIC ACID; BREAST-CARCINOMA; EXPRESSION; 12-LIPOXYGENASE; METASTASIS; 13-HODE; 5-LIPOXYGENASE; ANGIOGENESIS AB The effect of overexpression of 15-lipoxygenase-1 (15-LO-1) was studied in the human prostate cancer cell line, PC-3. Stable PC-3 cell lines were generated by transfection with 15-LO-1-sense (15-LOS), 15-LO-1-antisense (15-LOAS) or vector (Zeo) and selection with Zeocin. After characterization by RT-PCR, western and HPLC, a PC3-15LOS clone was selected that possessed 10-fold 15-LO-1 enzyme activity compared with parental PC-3 cells. The PC3-15LOAS clone displayed little or no 15-LO-1 activity. These PC-3 cell lines were characterized for properties of tumorigenesis. The proliferation rates of the cell lines were as follows: PC3-15LOS > PC-3 = PC3-Zeo > PC3-15LOAS. Addition of a specific 15-LO-1 inhibitor, PD146176, caused a dose-dependent inhibition of proliferation in vitro. Overexpression of 15-LO-1 also caused [IR]thymidine incorporation to increase by 4.0-fold (P < 0.01). Compared with parental and PC-3-Zeo cells, PC3-15LOS enhanced whereas PC3-15LOAS reduced the ability of PC-3 cells to grow in an anchorage-independent manner, as assessed by colony formation in soft agar. These data suggested a pro-tumorigenic role for 15-LO-1 in PC-3 cells in vitro. Therefore, to clarify the role of 15-LO-1 in vivo, the effect of 15-LO-1 expression on the growth of tumors in nude mice was investigated. The PC-3 cell lines were inoculated subcutaneously into athymic nude mice. The frequency of tumor formation was increased and the sizes of the tumors formed were much larger in the PC3-15LOS compared with PC3-15LOAS, parental PC-3 and PC-3-Zeo cells. Immunohistochemistry for 15-LO-1 confirmed expression throughout the duration of the experiment. The expression of factor VIII, an angiogenesis marker, in tumor sections was increased in tumors derived from PC3-15LOS cells and decreased in those from PC3-15LOAS cells compared with tumors from parental or Zeo cells. These data further supported the evaluation by ELISA of vascular endothelial growth factor (VEGF) secretion by PC-3 cells in culture. Secretion of this angiogenic factor was elevated in PC3-15LOS cells compared with the other cell lines. These results support a role for 15-LO-1 in a novel growth-promoting pathway in the prostate. C1 Emory Univ, Div Renal, Atlanta, GA 30322 USA. Emory Univ, Dept Anat Pathol, Atlanta, GA 30322 USA. Natl Inst Environm Hlth, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon. RP Kelavkar, UP (reprint author), Emory Univ, Div Renal, 1639 Pierce Dr, Atlanta, GA 30322 USA. NR 36 TC 95 Z9 104 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2001 VL 22 IS 11 BP 1765 EP 1773 DI 10.1093/carcin/22.11.1765 PG 9 WC Oncology SC Oncology GA 493AD UT WOS:000172199100004 PM 11698337 ER PT J AU Sun, XY Donald, SP Phang, JM AF Sun, XY Donald, SP Phang, JM TI Testosterone and prostate specific antigen stimulate generation of reactive oxygen species in prostate cancer cells SO CARCINOGENESIS LA English DT Article ID ADENOCARCINOMA; BINDING; PLASMA; ASSAY; PSA AB Prostate specific antigen, the clinical marker for prostate cancer, is a neutral serine protease whose function is to lyse seminal proteins. Recent work by our laboratory has suggested that prostate specific antigen stimulates the generation of reactive oxygen species in prostate cancer cells. Using 2',7'-dichlorofluorescin diacetate, a dye that fluoresces in the presence of hydrogen peroxide or hydroxyl radicals, we found that prostate specific antigen markedly stimulated reactive oxygen species generation in LNCaP cells. The effect was concentration dependent and its specificity was supported by the fact that anti-prostate specific antigen antibodies abolished the response. Since testosterone stimulates the production of prostate specific antigen, we considered that the reactive oxygen species response to testosterone may be linked to prostate specific antigen. We found that the testosterone effect on reactive oxygen species was blocked by flutamide and by anti-prostate specific antigen antibody. Additionally, though PC3 and DU145 could not respond to testosterone, they readily increased reactive oxygen species in response to prostate specific antigen. Focusing on the mechanism of the prostate specific antigen effect, we tested two other serine proteases, trypsin and chymotrypsin, but found no effect on reactive oxygen species in LNCaP cells. Nevertheless, serine protease inhibitors, alpha (1)-antichymotrypsin, alpha (2)-macroglobulin and Bowman-Birk inhibitor, blocked reactive oxygen species generation stimulated by prostate specific antigen. This apparent paradox was investigated with the use of a specific anti-'prostate specific antigen' antibody which recognizes an epitope away from the catalytic site and which does not inhibit protease activity. Despite the lack of inhibition of proteolytic activity, this antibody blocked the effect of prostate specific antigen on reactive oxygen species generation. These findings suggest that although the integrity of the prostate specific antigen molecule is necessary for stimulating reactive oxygen species generation, its proteolytic activity is not. The underlying mechanism is currently under investigation. C1 NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA. NR 18 TC 52 Z9 53 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2001 VL 22 IS 11 BP 1775 EP 1780 DI 10.1093/carcin/22.11.1775 PG 6 WC Oncology SC Oncology GA 493AD UT WOS:000172199100005 PM 11698338 ER PT J AU Newmark, HL Yang, K Lipkin, M Kopelovich, L Liu, Y Shinozaki, H AF Newmark, HL Yang, K Lipkin, M Kopelovich, L Liu, Y Shinozaki, H TI A Western-style diet induces benign and malignant neoplasms in the colon of normal C57Bl/6 mice SO CARCINOGENESIS LA English DT Article ID EPITHELIAL-CELL HYPERPROLIFERATION; NUTRITIONAL STRESS DIET; 4 COMPONENTS; MOUSE COLON; FOLATE; HYPERPLASIA; CANCER; DEFICIENCY; CALCIUM; DNA AB Decreased dietary intakes of calcium, vitamin D and folic acid have been suggested as risk factors for human colon cancer. We previously fed a Western-style diet (WD) containing reduced calcium, vitamin D and increased fat content to normal C57/B16 mice: hyperproliferation, hyperplasia and whole crypt dysplasias developed in the colon following WD administration. Utilizing the same diet, we now also decreased the levels of several nutrients that are required for biochemical reactions involving methyl group inadequacy, i.e. folic acid, methionine, choline and vitamin B-12. Dietary levels of these nutrients were reduced to nutrient-density levels approximating those consumed by large segments of human Western populations. This further modification of the WD resulted in adenoma and carcinoma development in normal mouse colon (P < 0.04 compared with AIN-76A diet). The results indicate, for the first time, that a semi-purified rodent diet designed to mimic the human Western diet can induce colonic tumors in normal mice without carcinogen exposure. C1 Strang Canc Prevent Ctr, New York, NY 10021 USA. NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Lipkin, M (reprint author), Strang Canc Prevent Ctr, New York, NY 10021 USA. FU NCI NIH HHS [N01 CN 75011] NR 34 TC 123 Z9 128 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2001 VL 22 IS 11 BP 1871 EP 1875 DI 10.1093/carcin/22.11.1871 PG 5 WC Oncology SC Oncology GA 493AD UT WOS:000172199100018 PM 11698351 ER PT J AU Hulla, JE AF Hulla, JE TI Letter to editor SO CARCINOGENESIS LA English DT Letter C1 Natl Inst Environm Hlth Sci, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Hulla, JE (reprint author), Natl Inst Environm Hlth Sci, Lab Environm Carcinogenesis & Mutagenesis, POB 12233, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2001 VL 22 IS 11 BP 1891 EP 1891 DI 10.1093/carcin/22.11.1891 PG 1 WC Oncology SC Oncology GA 493AD UT WOS:000172199100021 PM 11698354 ER PT J AU Neuss, M Crow, MT Chesley, A Lakatta, EG AF Neuss, M Crow, MT Chesley, A Lakatta, EG TI Apoptosis in cardiac disease - What is it - How does it occur SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Review DE apoptosis; heart; caspase; mitochondria; adrenergic receptor ID ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE-HEART-FAILURE; HYPOXIA-INDUCED APOPTOSIS; NECROSIS-FACTOR-ALPHA; FAILING HUMAN HEART; MYOCYTE CELL-DEATH; LEFT-VENTRICULAR DYSFUNCTION; ISCHEMIA-REPERFUSION INJURY; RENIN-ANGIOTENSIN SYSTEM; CARDIOMYOCYTES IN-VITRO AB This review will present a summary of a description of apoptotic pathways in the heart, followed by ways to measure it and the experimental and clinical evidence for the role of apoptosis in cardiac disease. An evaluation of the effectiveness of pharmacological and other therapeutic interventions in the prevention of apoptosis in the context of cardiac disease will also be presented. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. German Heart Inst, Dept Med Cardiol, D-13353 Berlin, Germany. RP Crow, MT (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 187 TC 25 Z9 25 U1 0 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD NOV PY 2001 VL 15 IS 6 BP 507 EP 523 DI 10.1023/A:1013715704835 PG 17 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 512JQ UT WOS:000173321600006 PM 11916360 ER PT J AU McNairy, SA AF McNairy, SA TI Message from the Director SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Editorial Material C1 NIH, Natl Ctr Res Resouces, Div Res Infrastruct, Bethesda, MD 20892 USA. RP McNairy, SA (reprint author), NIH, Natl Ctr Res Resouces, Div Res Infrastruct, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD NOV PY 2001 VL 47 IS 7 BP 1099 EP 1099 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 517AV UT WOS:000173589700002 ER PT J AU Bonville, CA Mehta, PA Krilov, LR Rosenberg, HF Domachowske, JB AF Bonville, CA Mehta, PA Krilov, LR Rosenberg, HF Domachowske, JB TI Epithelial cells infected with respiratory syncytial virus are resistant to the anti-inflammatory effects of hydrocortisone SO CELLULAR IMMUNOLOGY LA English DT Article DE paramyxovirus; hydrocortisone; interleukin-8; macrophage inflammatory; protein 1-alpha ID RANDOMIZED CONTROLLED TRIAL; TUMOR-NECROSIS-FACTOR; NEBULIZED BUDESONIDE; ORAL DEXAMETHASONE; KAPPA-B; BRONCHIOLITIS; EXPRESSION; INTERLEUKIN-8; PLACEBO; RANTES AB In this work we continue our study of the biochemical responses of respiratory epithelial cells to infection with human paramyxovirus pathogens. In our earlier studies, we detected elevated concentrations of the proinflammatory chemokines MIP-1alpha and IL-8 in upper and lower respiratory tract secretions from patients infected with respiratory syncytial virus (RSV). Here we demonstrate the same trend for individuals infected with parainfluenza virus (PIV), with elevated concentrations of MIP-1a and IL-8 (means of 309 +/- 51 and 2280 +/- 440 pg/ml/mg protein, respectively) detected in nasal wash samples from 17 patients with culture-positive PIV. Similar to our findings with RSV, cells of the HEp-2 epithelial line and primary cultures of human bronchial epithelial cells respond to PIV infection with production and release of both MIP-1alpha and IL-8. Addition of the glucocorticoid anti-inflammatory agent hydrocortisone (200-1000 ng/ml) attenuated the production of MIP-1alpha and IL-8 in PIV-infected cells while having minimal to no effect on the production of these mediators from cells infected with RSV. Neither virus infection resulted in a change in the total cellular concentration of glucocorticoid receptors, nor did hydrocortisone exert any differential effect on viral replication. As repression of chemokine production by epithelial cells is likely to result in diminished recruitment of proinflammatory leukocytes, these results may explain in part why glucocorticoid therapy reduces the symptoms associated with acute PIV infection, but have little to no effect in the overall outcome in the case of RSV. (C) 2001 Elsevier Science (USA). C1 SUNY Upstate Med Univ, Dept Pediat, Div Infect Dis, Syracuse, NY 13210 USA. Winthrop Univ Hosp, Dept Pediat, Mineola, NY 11501 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Domachowske, JB (reprint author), SUNY Upstate Med Univ, Dept Pediat, Div Infect Dis, 750 E Adams St, Syracuse, NY 13210 USA. NR 32 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV 1 PY 2001 VL 213 IS 2 BP 134 EP 140 DI 10.1006/cimm.2001.1869 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 524AH UT WOS:000173989400006 PM 11831875 ER PT J AU Inbaraj, JJ Kukielczak, BM Bilski, P Sandvik, SL Chignell, CF AF Inbaraj, JJ Kukielczak, BM Bilski, P Sandvik, SL Chignell, CF TI Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 1. Berberine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SUPEROXIDE; EPR; DNA AB Goldenseal is an herb which is widely used for many medical applications such as in eyewashes and skin lotions and which is currently undergoing testing by the National Toxicology Program. The main alkaloid constituent of Goldenseal is berberine. The topical application of Goldenseal or berberine to the skin or eyes raises the possibility that an adverse phototoxic reaction may result from an interaction between the alkaloid and light. We have therefore studied the photochemistry of berberine in different solvents and its phototoxicty to HaCaT keratinocytes. Irradiation of berberine in aqueous solutions does not generate O-1(2), but in CH2Cl2, O-1(2) is produced with a quantum yield phi = 0.34. With the aid of the electron paramagnetic resonance (EPR) spin trapping technique and 5,5-dimethyl-1-pyrroline N-oxide (DMPO), we have detected oxygen-centered radicals photogenerated by berberine in water and acetonitrile. In the latter solvent and in the absence of oxygen, the neutral berberine radical formed by one electron reduction was observed. Methanol radicals were detected by EPR in water/alcohol low-temperature glasses irradiated in the berberine long-wavelength absorption band. In such alcoholic glasses, we have also detected an EPR signal from the berberine triplet at 77 K, in contrast to aqueous glasses where neither triplet nor radicals were detectable. Our data show that, although a weak photosensitizer in water, berberine is able to produce both O-1(2) and radical species in a nonpolar environment. UVA irradiation of HaCaT keratinocytes in the presence of 50 muM berberine resulted in an 80% decrease in cell viability and a 3-fold increase in DNA damage as measured by the Comet assay. These findings suggest that exposure to sunlight or artificial light sources emitting UVA should be avoided when topical preparations derived from Goldenseal or containing berberine are used. C1 Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NR 23 TC 48 Z9 48 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 2001 VL 14 IS 11 BP 1529 EP 1534 DI 10.1021/tx0155247 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 496LA UT WOS:000172396000009 PM 11712911 ER PT J AU Potekhin, SA Melnik, TN Popov, V Lanina, NF Vazina, AA Rigler, P Verdini, AS Corradin, G Kajava, AV AF Potekhin, SA Melnik, TN Popov, V Lanina, NF Vazina, AA Rigler, P Verdini, AS Corradin, G Kajava, AV TI De novo design of fibrils made of short alpha-helical coiled coil peptides SO CHEMISTRY & BIOLOGY LA English DT Article DE coiled coil; design; fibril; peptide synthesis; stimulus-sensitive hydrogel ID LEUCINE-ZIPPER; TRANSCRIPTIONAL ACTIVATOR; CRYSTAL-STRUCTURE; PROTEIN DESIGN; HIGH AVIDITY; STABILITY; HYDROGELS; BUNDLE; DOMAIN; YEAST AB Background: The alpha -helical coiled coil structures formed by 25-50 residues long peptides are recognized as one of Nature's favorite ways of creating an oligomerization motif. Known de novo designed and natural Coiled Coils use the lateral dimension for oligomerization but not the axial one. Previous attempts to design alpha -helical peptides with a potential for axial growth led to fibrous aggregates which have an unexpectedly big and irregular thickness. These facts encouraged us to design a coiled coil peptide which self-assembles into Soluble oligomers with a fixed lateral dimension and whose alpha -helices associate in a staggered manner and trigger axial growth of the coiled coil. Designing the coiled coil with a large number of subunits, we also pursue the practical goal of obtaining a valuable scaffold for the construction of multivalent fusion proteins. Results: The designed 34-residue peptide self-assembles into long fibrils at slightly acid pH and into spherical aggregates at neutral pH. The fibrillogenesis is completely reversible upon pH change. The fibrils were characterized using circular dichroism spectroscopy, sedimentation diffusion, electron microscopy, differential scanning calorimetry and X-ray Fiber diffraction. The peptide was deliberately engineered to adopt the structure of a five-stranded coiled coil rope with adjacent alpha -helices, staggered along the fibril axis. As shown experimentally, the most likely structure matches the predicted five-stranded arrangement. Conclusions: The fact that the peptide assembles in an expected fibril arrangement demonstrates the credibility of our conception of design. The discovery of a short peptide with fibril-forming ability and stimulus-sensitive behavior opens new opportunities for a number of applications. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. Russian Acad Sci, Inst Cell Biophys, Pushchino 142292, Moscow Region, Russia. Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142292, Moscow Region, Russia. Ecole Polytech Fed Lausanne, Inst Phys Chem, CH-1015 Lausanne, Switzerland. Dictagene, CH-1066 Epalinges, Switzerland. Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland. RP Kajava, AV (reprint author), NIH, Ctr Mol Modeling, CIT, Bldg 12A, Bethesda, MD 20892 USA. RI Potekhin, Sergey/M-8274-2015; Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 37 TC 101 Z9 102 U1 1 U2 28 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD NOV PY 2001 VL 8 IS 11 BP 1025 EP 1032 DI 10.1016/S1074-5521(01)00073-4 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 507FR UT WOS:000173016800002 PM 11731294 ER PT J AU Ling, A AF Ling, A TI Electron beam CT in syndrome X SO CHEST LA English DT Editorial Material ID NORMAL CORONARY ARTERIOGRAMS; COMPUTED-TOMOGRAPHY; FOLLOW-UP; CLINICAL CHARACTERISTICS; ARTERY CALCIFICATION; CALCIUM; ATHEROSCLEROSIS; ULTRASOUND; DISEASE; EXTENT C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Ling, A (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1C-660, Bethesda, MD 20892 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2001 VL 120 IS 5 BP 1437 EP 1439 DI 10.1378/chest.120.5.1437 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 494GW UT WOS:000172274300007 PM 11713115 ER PT J AU Orbach, Y Lamb, ME Sternberg, KJ Williams, JMG Dawud-Noursi, S AF Orbach, Y Lamb, ME Sternberg, KJ Williams, JMG Dawud-Noursi, S TI The effect of being a victim or witness of family violence on the retrieval of autobiographical memories SO CHILD ABUSE & NEGLECT LA English DT Article DE family violence; autobiographical memories; depression ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD PHYSICAL ABUSE; LONG-TERM-MEMORY; DOMESTIC VIOLENCE; DEPRESSION; ORGANIZATION; CHILDREN; SPECIFICITY; SUICIDE; PARENTS AB Objective: This study was designed to determine whether greater reliance on general memory retrieval in children was related to depression, and whether family violence affected the specificity of children's memory retrieval. Method: We compared children who had experienced some form of family violence with children who had never experienced any form of family violence, based on their responses to questions concerning child-parent and interparental disagreements. Results: As expected, there was a positive correlation between the extent of "generic-categoric" memory retrieval and depression level. There was no evidence, however, that autobiographical memory was affected by family violence. Conclusions: This study is the first to report significant associations between depression and autobiographical memory style in children. The results suggest that the effect of family violence on children's memory retrieval may be mediated by depression. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD 20892 USA. Univ Wales, Sch Psychol, Bangor, Gwynedd, Wales. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, Rockledge 1,Suite 8048,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 53 TC 25 Z9 25 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD NOV PY 2001 VL 25 IS 11 BP 1427 EP 1437 DI 10.1016/S0145-2134(01)00283-6 PG 11 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA 493WW UT WOS:000172247300003 PM 11766009 ER PT J AU Dionne, RA Khan, AA Gordon, SM AF Dionne, RA Khan, AA Gordon, SM TI Analgesia and COX-2 inhibition SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 1st International Congress on Natural Spa Therapy CY NOV 21-24, 2001 CL DEAD SEA, ISRAEL DE selective COX-2 inhibitors; microdialysis; acute pain ID ACUTE POSTOPERATIVE PAIN; IMPACTED 3RD MOLARS; IMMUNOREACTIVE BRADYKININ; PROSTAGLANDIN E-2; CONTROLLED TRIAL; BETA-ENDORPHIN; TISSUE-LEVELS; DENTAL PAIN; IBUPROFEN; SUPPRESSION AB While non-steroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain and rheumatoid arthritis, toxicity associated with chronic administration limits their benefit-to-risk relationship in many patients. A series of studies is reviewed that assesses the relationship between cytokines released at the site of tissue injury and NSAID analgesia, and the in vivo selectivity of a selective cyclooxygenase (COX)-2 inhibitor (celecoxib) in comparison to a dual COX-1/COX-2 inhibitor (ketorolac). Three replicate studies in the oral surgery model of acute pain used submucosal microdialysis sample collection for the measurement of prostaglandin E-2 (PGE(2); a product of both COX-1 and COX-2) and thromboxane B-2 (as a biomarker for COX-1 activity) with parallel assessments of pain. The time course of PGE(2) production was consistent with early release due to COX-1 activity followed by increased production 2-3 hours after surgery, consistent with COX-2 expression. Ketorolac 30 mg at pain onset suppressed both pain and peripheral PGE(2) levels. Ketorolac 1 mg either at the site of injury or intramuscularly also produced analgesia but without any effect on peripheral PGE2 levels. Celecoxib selectively suppressed PGE2 but not TxB(2) at time points consistent with COX-2 activity, while producing analgesia. These studies demonstrate the ability to assess the time course and selective effects of COX-2 inhibitors in vivo and suggest that suppression of COX-2 mediated PGE, is temporally related to NSAID analgesia. C1 Natl Inst Dent & Craniofacial Res, NIH, Washington, DC USA. RP Dionne, RA (reprint author), 1351 28th St NW, Washington, DC 20007 USA. NR 41 TC 15 Z9 19 U1 0 U2 2 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD NOV-DEC PY 2001 VL 19 IS 6 SU 25 BP S63 EP S70 PG 8 WC Rheumatology SC Rheumatology GA 485ZL UT WOS:000171793300012 PM 11695255 ER PT J AU Ikonen, T Matikainen, M Mononen, N Hyytinen, ER Helin, HJ Tommola, S Tammela, TLJ Pukkala, E Schleutker, J Kallioniemi, OP Koivisto, PA AF Ikonen, T Matikainen, M Mononen, N Hyytinen, ER Helin, HJ Tommola, S Tammela, TLJ Pukkala, E Schleutker, J Kallioniemi, OP Koivisto, PA TI Association of E-cadherin germ-line alterations with prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID FAMILIAL GASTRIC-CANCER; SUSCEPTIBILITY LOCUS; CELL-ADHESION; COLORECTAL-CANCER; GENE; MUTATIONS; EXPRESSION; RISK; CHROMOSOME; CARCINOMA AB In our recent cancer registry-based study, the incidence of gastric carcinoma was increased up to 5-fold in male relatives of early-onset prostate cancer (PCA) patients. This association may reflect the influence of genetic factors predisposing individuals to both tumor types. Germ-line mutations of the CDH1 gene at 16q have recently been associated with familial gastric cancer. Furthermore, two genome-wide linkage studies of PCA recently reported positivity at 16q. We therefore identified families and individual patients with both gastric and PCA and investigated whether the CDH1 gene mutations were involved in cancer predisposition in these cases. Fifteen of the 180 Finnish hereditary PCA families (8.3%) bad one or more gastric cancer cases. No truncating or splice site CDH1 mutations were identified by PCR single-strand conformational polymorphism in these families or in eight individual patients who had both prostate and gastric cancer. However, a novel S270A missense mutation in exon 6 of the CDH1 gene was seen in a single family with four prostate and two gastric cancers. A large-scale population-based survey indicated a higher prevalence of S270A among both familial PCA cases (3.3%; n = 120; P = 0.01) and unselected PCA patients (1.5%; n = 472; P = 0.12) as compared with blood donors serving as population controls (0.5%; n = 923). We conclude that individual rare mutations and polymorphisms in the CDH1 gene, such as S270A, may contribute to the onset of PCA and warrant further investigations in other populations. However, the CDH1 gene does not appear to explain the link between prostate and gastric cancer. C1 Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Clin Genet, FIN-33521 Tampere, Finland. Tampere Univ Hosp, Dept Pathol, FIN-33521 Tampere, Finland. Finnish Canc Registry, FIN-00170 Helsinki, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Ikonen, T (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, POB 607, FIN-33101 Tampere, Finland. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NHGRI NIH HHS [N01-HG-55389] NR 47 TC 30 Z9 32 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 BP 3465 EP 3471 PG 7 WC Oncology SC Oncology GA 491JX UT WOS:000172106200024 PM 11705864 ER PT J AU Sato, N Kobayashi, H Saga, T Nakamoto, Y Ishimori, T Togashi, K Fujibayashi, Y Konishi, J Brechbiel, MW AF Sato, N Kobayashi, H Saga, T Nakamoto, Y Ishimori, T Togashi, K Fujibayashi, Y Konishi, J Brechbiel, MW TI Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice SO CLINICAL CANCER RESEARCH LA English DT Article ID STARBURST POLYAMIDOAMINE DENDRIMERS; SUICIDE GENE-THERAPY; MONOCLONAL-ANTIBODY; PLASMID DNA; CATIONIC LIPOSOMES; EFFICIENT TRANSFER; PAMAM DENDRIMERS; NUDE-MOUSE; IN-VIVO; OLIGONUCLEOTIDES AB To establish an effective nonviral gene delivery and a corresponding imaging method. for i.p.-disseminated tumors, various oligonucleotide-carrier complexes were synthesized, and their in vitro and in vivo properties were examined. The 20-mer multiamino-linked oligonucleotide (oligo), synthesized as antisense against the c-erbB-2 sequence, and the 3'-biotinylated form of the same oligonucleotide (oligo-Bt) were In-111 labeled through a diethylenetriaminepentaacetic acid chelate. In-111-oligo was mixed with generation 4 polyamidoamine dendrimer (G4) or with biotinylated G4 (G4-Bt), which are positively charged to form electrostatic complexes. In-111-oligo/G4-Bt and In-111-oligo-Bt were conjugated to avidin (In-111-oligo/G4-Av and In-111-oligo-Av, respectively). In-111-oligo/G4. In-111-oligo/G4-Av, In-111-oligo-Av, and carrier-free In-111-oligo (2.96 kBq/22.4-45.9 ng of oligo) were examined for internalization in vitro in human ovarian cancer cells (SHIN3). Biodistribution of In-111-oligo-carrier complexes or In-111-oligo was examined in normal (n = 4-7) or i.p. SHIN3 tumor-bearing (n = 6-10) mice 2-24 h after Lp. injection (74 kBq/125-300 ng). Scintigraphy of i.p. tumor-bearing and normal mice was performed at various times postinjection of In-111-oligo-carrier complex or In-111-oligo (1.85 MBq/2.2 ng). In-111-oligo-carrier complexes bound to the tumor cells were internalized at a rate of 34-56% at 24 h. In vivo, G4, G4-Av, and Av significantly enhanced tumor delivery of In-111-oligo [9.1, 14.5, and 24.4% of injected dose per g of tissue (ID/g) at 24 h; P < 0.05, < 0.01, and < 0.0001, respectively] compared with delivery without carrier (0.8% ID/g). Scintigrams of In-111-oligo delivered to the i.p.-disseminated tumors by the carriers were successfully obtained. In conclusion, G4, G4-Av, and Av can effectively deliver In-111-oligo to i.p.-dissenunated tumors. In-111-oligo-carrier complexes also have potential as tracers for imaging and monitoring of gene delivery. C1 Kyoto Univ, Hitachi Med Co,Grad Sch Med, Dept Diagnost & Intervent Imagiol, Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Dept Nucl Med & Diagnost Imaging, Kyoto 6068507, Japan. Fukui Med Univ, Biomed Imaging Res Ctr, Mol Imaging Div, Fukui 9101193, Japan. NCI, Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), Kyoto Univ, Hitachi Med Co,Grad Sch Med, Dept Diagnost & Intervent Imagiol, Sakyo Ku, 54 Kawaharacho, Kyoto 6068507, Japan. NR 41 TC 84 Z9 84 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 BP 3606 EP 3612 PG 7 WC Oncology SC Oncology GA 491JX UT WOS:000172106200043 PM 11705883 ER PT J AU Overmoyer, B Robertson, K Persons, M Shenk, R Lewin, J Jesberger, J Ziats, N Tserng, K Hoppel, C Hartman, P Wasman, J Abdul-Karim, F Waas, J Pluda, J McCrae, K Remick, S AF Overmoyer, B Robertson, K Persons, M Shenk, R Lewin, J Jesberger, J Ziats, N Tserng, K Hoppel, C Hartman, P Wasman, J Abdul-Karim, F Waas, J Pluda, J McCrae, K Remick, S TI A phase I pharmacokinetic and pharmacodynamic study of SU5416 and doxorubicin in inflammatory breast cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 31 BP 3659S EP 3659S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800032 ER PT J AU Yazawa, H Roessler, PG Wiltrout, RH Watanabe, M AF Yazawa, H Roessler, PG Wiltrout, RH Watanabe, M TI Delayed in vivo growth of Lewis lung carcinoma cells that have been genetically engineered to secrete the kringle 5 domain of plasminogen. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 44 BP 3662S EP 3662S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800045 ER PT J AU Rapisarda, A Uranchimeg, B Scudiero, DA Selby, MH Sausville, EA Shoemaker, RH Melillo, G AF Rapisarda, A Uranchimeg, B Scudiero, DA Selby, MH Sausville, EA Shoemaker, RH Melillo, G TI Identification of novel inhibitors of HIF-1 transcripitonal activation and VEGF expression using a high throughput targeted screen. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 SAIC Frederick, Frederick, MD USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 54 BP 3664S EP 3664S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800055 ER PT J AU Weeraratna, AT Bittner, M Jiang, Y Meltzer, P Trent, JM AF Weeraratna, AT Bittner, M Jiang, Y Meltzer, P Trent, JM TI Investigation of Wnt5a as a molecular target for invasive melanoma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 78 BP 3669S EP 3669S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800080 ER PT J AU Steeg, P Hartsough, MT Clare, S Ouatas, T AF Steeg, P Hartsough, MT Clare, S Ouatas, T TI Increased nm23-H1 metastasis suppressor gene expression in human breast carcinoma cells by medroxyprogesterone acetate. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Northwestern Univ, Evanston, IL 60208 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 83 BP 3670S EP 3670S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800084 ER PT J AU Lee, S Nguyen, P Stevens, LM Khanna, C Linehan, WM Helman, LJ Kim, J Horisberger, MA Trepel, JB Mushinski, JF AF Lee, S Nguyen, P Stevens, LM Khanna, C Linehan, WM Helman, LJ Kim, J Horisberger, MA Trepel, JB Mushinski, JF TI Inhibition of tumor cell motility by the interferon-inducible GTPase MxA. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Novartis Pharma AG, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 88 BP 3671S EP 3671S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800089 ER PT J AU Paciotti, GF Myer, LD Kim, TH Wang, S Alexander, HR Weinreich, D Tamarkin, L AF Paciotti, GF Myer, LD Kim, TH Wang, S Alexander, HR Weinreich, D Tamarkin, L TI Colloidal gold: A novel colloidal nanoparticle vector for tumor-directed drug delivery. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Cytimmune Sci Inc, College Pk, MD USA. NIH, NCI, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 104 BP 3673S EP 3674S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800104 ER PT J AU Elezra, M Ford, H Marquez, VE Johns, DG Agbaria, R AF Elezra, M Ford, H Marquez, VE Johns, DG Agbaria, R TI Thymidine triphosphate depletion enhances N-methanocarbathymidine phosphorylation and DNA incorporation in murine colon cancer cells expressing herpes simplex virus thymidine kinase. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. NCI, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 118 BP 3676S EP 3677S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800118 ER PT J AU Gupta, S Zgodinski, J Tabibi, E Vishnuvajjala, R AF Gupta, S Zgodinski, J Tabibi, E Vishnuvajjala, R TI Compatibility studies of NSC 330507, 17-AAG, clinical formulation in commonly used intravenous fluids. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Ben Venue Lab Inc, Bedford, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 119 BP 3677S EP 3677S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800119 ER PT J AU Wulfkuhle, JD McLean, K Sgroi, D Sahin, A Petricoin, E Steeg, P AF Wulfkuhle, JD McLean, K Sgroi, D Sahin, A Petricoin, E Steeg, P TI Proteomic analysis of breast cancer progression. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, NCI, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 153 BP 3684S EP 3684S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800152 ER PT J AU Monks, A Connelly, JW Sausville, EA AF Monks, A Connelly, JW Sausville, EA TI Determination of gene expression changes in MCF-7 induced by a novel antitumor agent, 2-(4-amino-3-methylphenyl) benzothiazole, using serial analysis of gene expression (SAGE) libraries. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, DTP, DCTD, Rockville, MD USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 166 BP 3686S EP 3686S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800165 ER PT J AU Qiu, TH Alkharouf, NW Hunter, KW Liu, ET AF Qiu, TH Alkharouf, NW Hunter, KW Liu, ET TI Analysis of gene expression profiles in MMTV-PyMT transgenic mice in different genomic background. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 165 BP 3686S EP 3686S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800164 ER PT J AU Jezequel, P Campion, L El-Kahloun, A Cherel, M Ricolleau, G Classe, J Fiche, M Dravet, F Fumoleau, P Deporte, R AF Jezequel, P Campion, L El-Kahloun, A Cherel, M Ricolleau, G Classe, J Fiche, M Dravet, F Fumoleau, P Deporte, R TI Breast cancer subtyping by gene expression profiling using an unsupervised classification methodology. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Ctr Rene Gauducheau, Saint Herblain, France. NHGRI, CGB, NIH, Bethesda, MD 20892 USA. RI Jezequel, Pascal/K-8206-2015; Cherel, Michel/F-8298-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 172 BP 3687S EP 3688S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800170 ER PT J AU Wei, JS Khan, J Ringner, M Ladanyi, M Meltzer, PS AF Wei, JS Khan, J Ringner, M Ladanyi, M Meltzer, PS TI Histogenesis and molecular subclassification of Ewing's sarcoma using cDNA microarrays. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 170 BP 3687S EP 3687S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800168 ER PT J AU Bichsel, VE Calvert, VS Charboneau, L Trock, BJ Sgroi, DC Liotta, LA Petricoin, EF AF Bichsel, VE Calvert, VS Charboneau, L Trock, BJ Sgroi, DC Liotta, LA Petricoin, EF TI Profiling of signal transduction pathways in laser capture micro-dissected breast cancer epithelium. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, Natl Canc Inst, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 202 BP 3693S EP 3693S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800199 ER PT J AU Reed, E Sarosy, GA Gordon, AN Weems, G Herdrich, L AF Reed, E Sarosy, GA Gordon, AN Weems, G Herdrich, L TI Clinical activity of Irofulven in pretreated advanced ovarian cancer (AOC) patients. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. US Oncol, Dallas, TX USA. MG1 Pharma Inc, Bloomington, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 219 BP 3697S EP 3697S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800216 ER PT J AU Yu, X Guo, Z Marcu, MG Neckers, L Chen, G Nguyen, DM Schrump, DS AF Yu, X Guo, Z Marcu, MG Neckers, L Chen, G Nguyen, DM Schrump, DS TI Depsipeptide-mediated apoptosis coincides with depletion of mutant p53, erbB1, erbB2, and raf-1 protein levels in lung cancer cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 228 BP 3698S EP 3698S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800225 ER PT J AU Scudiero, D Selby, M Silvers, T Laudeman, J Clopper, S Grams-Fowler, J Tenen, D Radomska, H Sausville, E Shoemaker, R AF Scudiero, D Selby, M Silvers, T Laudeman, J Clopper, S Grams-Fowler, J Tenen, D Radomska, H Sausville, E Shoemaker, R TI Development of a cell-based high throughput screen for inducers of C/EBP alpha. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. Harvard Univ, Inst Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 246 BP 3702S EP 3702S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800243 ER PT J AU Zhang, Z Li, J Yao, R Wang, Y Lubet, R You, M AF Zhang, Z Li, J Yao, R Wang, Y Lubet, R You, M TI Generating tumors for chemoprevention and chemotherapeutic studies employing transgenic mice with a dominant negative mutation in the p53 tumor suppressor gene. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 252 BP 3703S EP 3704S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800249 ER PT J AU Friedrichs, WE Degraffenried, LA Green, JE Burgering, B Hidalgo, M AF Friedrichs, WE Degraffenried, LA Green, JE Burgering, B Hidalgo, M TI A strategy to combine tissue specificity with hormone-independent regulation into a complex vector to improve animal models of prostate and breast cancers with unregulated Akt kinase activity. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NIH, Bethesda, MD 20892 USA. Univ Utrecht, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 264 BP 3706S EP 3706S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800261 ER PT J AU Xu, W Marcu, MG Yuan, X Mimnaugh, EG Patterson, C Neckers, L AF Xu, W Marcu, MG Yuan, X Mimnaugh, EG Patterson, C Neckers, L TI Identification of a novel E3 ubiquitin ligase that may mediate geldanamycin-induced ErbB2 degradation. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 275 BP 3708S EP 3708S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800271 ER PT J AU Hochster, H Liebes, L Buckley, M Sorich, J Fry, D Hamilton, A Wright, J Muggia, F AF Hochster, H Liebes, L Buckley, M Sorich, J Fry, D Hamilton, A Wright, J Muggia, F TI Inhibition of H-ras membrane binding and topoisomerase-1 in a phase I trial of topotecan combined with the farnesyl transferase inhibitor, R115777 (Zarnestra). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NYU, Sch Med, New York, NY USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 281 BP 3710S EP 3710S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800277 ER PT J AU Komiya, T Tamura, K Fukuoka, M Kelley, MJ Kubo, A Kaye, FJ Matsunaga, S Fusetani, N Nakagawa, K AF Komiya, T Tamura, K Fukuoka, M Kelley, MJ Kubo, A Kaye, FJ Matsunaga, S Fusetani, N Nakagawa, K TI Ritterazine B, a new cytotoxic marine product, induces apoptosis and G2/M arrest. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Natl Naval Med Res Inst, NCI, Bethesda, MD USA. Kinki Univ, Sch Med, Osakasayama, Japan. Duke Univ, Durham, NC USA. Univ Tokyo, Tokyo, Japan. RI kaye, frederic/E-2437-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 309 BP 3716S EP 3716S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800305 ER PT J AU Sayers, TJ Brooks, A Seki, N Murphy, WJ Elliott, PJ AF Sayers, TJ Brooks, A Seki, N Murphy, WJ Elliott, PJ TI The proteasome inhibitor PS-341 sensitizes tumor cells to TRAIL-mediated apoptosis. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, SAIC Frederick, Frederick, MD 21701 USA. Millennium Pharmaceut, Cambridge, MA USA. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 319 BP 3718S EP 3718S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800315 ER PT J AU Yu, Q He, M Liu, E AF Yu, Q He, M Liu, E TI Transcriptional regulation of c-Myc-mediated sensitization to DNA damage induced apoptosis. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Gaithersburg, MD USA. RI Liu, Edison/C-4141-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 327 BP 3719S EP 3719S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800323 ER PT J AU Leach, RA Zhang, P Ng, P Caridha, D Asher, L Novak, M Smith, WJ Zeichner, SL Chiang, PK AF Leach, RA Zhang, P Ng, P Caridha, D Asher, L Novak, M Smith, WJ Zeichner, SL Chiang, PK TI Induction of apoptosis by an alkylating agent in Jurkat cells by inhibiting PDK1-Akt pathway. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Walter Reed Army Inst Res, Silver Spring, MD USA. NCI, NIH, Bethesda, MD 20892 USA. US Army Med Inst Chem Def, Aberdeen Proving Ground, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 340 BP 3721S EP 3722S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800336 ER PT J AU Kosakowska-Cholody, T Cholody, WM Hollingshead, MG Michejda, CJ AF Kosakowska-Cholody, T Cholody, WM Hollingshead, MG Michejda, CJ TI WMC79, a potent agent against colon and pancreatic cancers, induces apoptosis through a p53-dependent pathway. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 343 BP 3722S EP 3722S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800339 ER PT J AU Piekarz, R Robey, R Sandor, V Fojo, AT Bakke, S Wilson, W Kingma, D Turner, M Tucker, E Bates, SE AF Piekarz, R Robey, R Sandor, V Fojo, AT Bakke, S Wilson, W Kingma, D Turner, M Tucker, E Bates, SE TI Potential value of the histone deacetylase inhibitor depsipeptide (FR901228) in the treatment of peripheral and cutaneous T-cell lymphoma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 360 BP 3726S EP 3726S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800355 ER PT J AU Covey, JM Feng, WY Zheng, H Chan, KK AF Covey, JM Feng, WY Zheng, H Chan, KK TI Stability and preliminary pharmacokinetics of the bradykinin antagonist polypeptide B201 in the mouse determined by electrospray LC/MS/MS. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, DCTD, Dev Therapeut Program, Rockville, MD USA. Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 396 BP 3733S EP 3733S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800390 ER PT J AU Loaiza-Perez, AI Vistica, D Kenney, S Hose, C Ciolino, H Yeh, G Trepel, J Sausville, E AF Loaiza-Perez, AI Vistica, D Kenney, S Hose, C Ciolino, H Yeh, G Trepel, J Sausville, E TI The aryl hydrocarbon receptor mediates sensitivity of MCF-7 breast cancer cells to the antitumor agent aminoflavone NSC 686288. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, Natl Canc Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 413 BP 3737S EP 3737S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800407 ER PT J AU Tarasova, NI Amadei, G Seth, R Hrycyna, C Gottesman, M Michejda, C AF Tarasova, NI Amadei, G Seth, R Hrycyna, C Gottesman, M Michejda, C TI New paradigm for the development of inhibitors of ABC transporters and other polytopic membrane proteins. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 419 BP 3738S EP 3738S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800413 ER PT J AU Abraham, J Edgerly, M Wilson, R Medina, W Hermonstine, L Rutt, A Bakke, S Robey, R Grem, J Bates, S Fojo, T Chen, C Dwyer, A Goldspiel, B Van Tellingen, O Norris, D Steiner, J Waterfall, J AF Abraham, J Edgerly, M Wilson, R Medina, W Hermonstine, L Rutt, A Bakke, S Robey, R Grem, J Bates, S Fojo, T Chen, C Dwyer, A Goldspiel, B Van Tellingen, O Norris, D Steiner, J Waterfall, J TI A study of the novel P-glycoprotein (P-gp) antagonist, XR9576 in combination with vinorelbine. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD USA. Antoni Van Leeuwenhoek Hosp, Amsterdam, Netherlands. Xenova Ltd, Slough, Berks, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 426 BP 3739S EP 3740S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800420 ER PT J AU Lubet, R You, M Ruchon, Y End, D Wouters, W Christov, K Grubbs, C AF Lubet, R You, M Ruchon, Y End, D Wouters, W Christov, K Grubbs, C TI Therapeutic and chemopreventive effects of R115777, a farnesyl-transferase inhibitor (FTI), on methylnitrosourea (MNU)-induced rat mammary cancer and effects on potential biomarkers. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. Ohio State Univ, Columbus, OH 43210 USA. Johnson & Johnson, Titusville, NJ USA. Univ Illinois, Chicago, IL USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 453 BP 3745S EP 3745S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800446 ER PT J AU Watanabe, M Wiltrout, RH AF Watanabe, M Wiltrout, RH TI Differential impact of local production interleukin-2 and interleukin-12 on initial appearance and long-term progression of B16F10 melanoma in mice. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 501 BP 3754S EP 3754S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800494 ER PT J AU Liu, K Rosenberg, SA AF Liu, K Rosenberg, SA TI Transduction of an interleukin-2 (IL2) gene into human melanoma reactive lymphocytes results in their continued growth in the absence of exogenous IL2 and maintains their specific antitumor activity. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 504 BP 3755S EP 3755S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800497 ER PT J AU Kallioniemi, A Hyman, E Kauraniemi, P Monni, O Mousses, S Bittner, M Chen, Y Elkahloun, A Kallioniemi, O AF Kallioniemi, A Hyman, E Kauraniemi, P Monni, O Mousses, S Bittner, M Chen, Y Elkahloun, A Kallioniemi, O TI Genome-wide copy number and expression analysis for identification of putative molecular targets in cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, NHGRI, Bethesda, MD 20892 USA. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 529 BP 3760S EP 3760S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800521 ER PT J AU Chandra, J Mow, B Weisberg, E Griffin, J Sausville, EA Tefferi, A Kaufmann, SH AF Chandra, J Mow, B Weisberg, E Griffin, J Sausville, EA Tefferi, A Kaufmann, SH TI Effects of the bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on leukemic cells in vitro. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 571 BP 3768S EP 3769S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800563 ER PT J AU Dennis, PA Brognard, J Sun, H Jung, M Streicher, S Kozikowski, A AF Dennis, PA Brognard, J Sun, H Jung, M Streicher, S Kozikowski, A TI Molecular modeling-based synthesis of novel Akt inhibitors that cause tumor cell apoptosis. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 574 BP 3769S EP 3769S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800566 ER PT J AU Gussio, R McGrath, CF Burnett, JC Zaharevitz, DW Sausville, EA AF Gussio, R McGrath, CF Burnett, JC Zaharevitz, DW Sausville, EA TI A supermolecule approach to the structural characterization of cyclin-depenent kinases. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 582 BP 3771S EP 3771S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800574 ER PT J AU Marcu, MG Hendershot, L Bertolotti, A Ron, D Neckers, L AF Marcu, MG Hendershot, L Bertolotti, A Ron, D Neckers, L TI Heat shock protein 90 (Hsp90) stabilizes IRE1 and PERK, transmembrane kinases of the endoplasmic reticulum that mediate the unfolded protein response. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 620 BP 3778S EP 3778S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800612 ER PT J AU Isaacs, J Jung, Y Mimnaugh, EG Neckers, L AF Isaacs, J Jung, Y Mimnaugh, EG Neckers, L TI Geldanamycin destabilizes HIF-1 alpha protein and antagonizes its function via a VHL-independent pathway. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 627 BP 3779S EP 3779S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800619 ER PT J AU Mimnaugh, EG Neckers, L AF Mimnaugh, EG Neckers, L TI Biologic rationale for the combination of an Hsp90 antagonist with a proteasome inhibitor. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 623 BP 3779S EP 3779S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800615 ER PT J AU Becker, KF Mages, J Kremmer, E Senekowitsch, R Pastan, I Hoefler, H AF Becker, KF Mages, J Kremmer, E Senekowitsch, R Pastan, I Hoefler, H TI Personalized medicine for gastric cancer patients: individual gene mutations as targets for tumor-specific interventions. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 GSF Natl Res Ctr Munich, Neuherberg, Germany. Tech Univ Munich, D-8000 Munich, Germany. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 648 BP 3784S EP 3784S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800641 ER PT J AU Mandler, R Hinson, ER Davis, MY Sausville, EA Newman, DJ Yang, D Roettinger, AJ Brechbiel, MW Waldmann, TA AF Mandler, R Hinson, ER Davis, MY Sausville, EA Newman, DJ Yang, D Roettinger, AJ Brechbiel, MW Waldmann, TA TI Herceptin : geldanamycin immunoconjugates augment the efficacy of Herceptin in mice bearing HER2-overexpressing xenografts. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, CCR, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. NCI, Rockville, MD USA. Georgetown Univ, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 658 BP 3786S EP 3786S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800651 ER PT J AU Desiervi, A Diggs, J Lahusen, T Patel, V Sausville, EA Gutkind, S Senderowicz, AM AF Desiervi, A Diggs, J Lahusen, T Patel, V Sausville, EA Gutkind, S Senderowicz, AM TI Perifosine, a novel oral antitumor alkylphospholipid, arrest cells in G(1)/S and G(2)/M due to a p53-independent induction of p21(waf1). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. NCI, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 679 BP 3790S EP 3790S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800672 ER PT J AU Lahusen, T Orellana, E Senderowicz, AM AF Lahusen, T Orellana, E Senderowicz, AM TI Alsterpaullone (alp), a novel cyclin-dependent kinase inhibitor, induces apoptosis by activation of both caspase 8 and caspase 9 cascades. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 689 BP 3792S EP 3792S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800682 ER PT J AU Lahusen, T Sy, T Hollingshead, M Sausville, EA Senderowicz, AM AF Lahusen, T Sy, T Hollingshead, M Sausville, EA Senderowicz, AM TI Rapamycin promotes G(1)/S arrest and antitumor effects by an FKBP-dependent downregulation of cyclin D3 in prostate carcinoma cell lines. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD USA. NCI, DTP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 688 BP 3792S EP 3792S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800681 ER PT J AU Bhonde, M Magrini, R Lenz, M Hanski, M Kobalz, U Notter, M Sausville, E Scherubl, H Zeitz, M Hanski, C AF Bhonde, M Magrini, R Lenz, M Hanski, M Kobalz, U Notter, M Sausville, E Scherubl, H Zeitz, M Hanski, C TI Modulation of cytotoxicity of UCN-01 (7-hydroxystaurosporine) by lesions in p53 gene and in mismatch repair system. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Clin Benjamin Franklin, Berlin, Germany. NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 693 BP 3793S EP 3793S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800686 ER PT J AU Adams, DJ Gamscik, MP Colvin, OM Flowers, JL Chen, S Hollister, BA Manikumar, G Wani, MC Wall, ME Pommier, YG AF Adams, DJ Gamscik, MP Colvin, OM Flowers, JL Chen, S Hollister, BA Manikumar, G Wani, MC Wall, ME Pommier, YG TI Peptidyl-camptothecins are effective topoisomerase I inhibitors and potent antitumor agents. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Duke Univ, Durham, NC USA. So Piedmont Conservat Res Ctr, Morrisville, NC USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 704 BP 3795S EP 3795S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800696 ER PT J AU Cunliffe, H Walker, R Scherr, M Rossi, JJ Meltzer, PS AF Cunliffe, H Walker, R Scherr, M Rossi, JJ Meltzer, PS TI Use of cDNA microarrays to identify signalling pathways associated with AIB1 overexpression in breast cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. Hannover Med Sch, D-3000 Hannover, Germany. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 735 BP 3801S EP 3801S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800726 ER PT J AU Azorsa, DO Young, K Khan, J Meltzer, PS AF Azorsa, DO Young, K Khan, J Meltzer, PS TI Inhibition of transactivation mediated by the alveolar rhabdomyosarcoma fusion oncoprotein PAX3-FKHR using anti-PAX3-FKHR-specific intrabodies. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NHGRI, Bethesda, MD 20892 USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 738 BP 3802S EP 3802S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800729 ER PT J AU Chung, EJ Hwang, S Nguyen, P Kim, J Kim, JW Henkart, PA Bottaro, DP Soon, L Muraiso, K Bonvini, P Rubin, JS Trepel, JB AF Chung, EJ Hwang, S Nguyen, P Kim, J Kim, JW Henkart, PA Bottaro, DP Soon, L Muraiso, K Bonvini, P Rubin, JS Trepel, JB TI beta-catenin regulates leukemic cell adhesion, growth and survival. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 748 BP 3804S EP 3804S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800739 ER PT J AU Grecula, JC Grever, M Gupta, N Goodman, J Barth, R Christoforidis, G Miles, D Renschler, M Maher, J Wang, D Kangarlu, A Jalil, AA Bauer, C McGregor, J Newton, H Chakeres, D Chaudhury, A Young, D Fischer, B Adams, D Balcerzak, S Ivy, P AF Grecula, JC Grever, M Gupta, N Goodman, J Barth, R Christoforidis, G Miles, D Renschler, M Maher, J Wang, D Kangarlu, A Jalil, AA Bauer, C McGregor, J Newton, H Chakeres, D Chaudhury, A Young, D Fischer, B Adams, D Balcerzak, S Ivy, P TI Phase I trial of motexafin gadolinium (Gd-Tex) during G-knife boost for glioblastoma multiforme. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Ohio State Univ, Columbus, OH 43210 USA. Pharmacycl Inc, Sunnyvale, CA USA. NCI, Bethesda, MD 20892 USA. RI Gupta, Nilendu/E-3171-2011; Grecula, John/E-3149-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 762 BP 3807S EP 3807S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800753 ER PT J AU Fojo, AT Kotz, H Abraham, J Agrawal, M Bates, SE Balis, F Widemann, B Bakke, S Edgerly, M Rutt, A Damle, B Sonnichsen, D Lebwohl, D AF Fojo, AT Kotz, H Abraham, J Agrawal, M Bates, SE Balis, F Widemann, B Bakke, S Edgerly, M Rutt, A Damle, B Sonnichsen, D Lebwohl, D TI A phase I clinical trial of BMS-247550 (NSC 710428), an epothilone B analog, in patients with refractory neoplasms. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. W Virginia Univ, Morgantown, WV 26506 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Wallingford, CT 06492 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 774 BP 3809S EP 3809S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800765 ER PT J AU Poruchynsky, MS Annable, T Kim, J Fojo, T Loganzo, F Greenberger, L AF Poruchynsky, MS Annable, T Kim, J Fojo, T Loganzo, F Greenberger, L TI Tumor cells resistant to a tubulin-depolymerizing hemiasterlin analog, WAY-174286, display different resistance mechanisms, including mutations in alpha- or beta-tubulin. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Wyeth Ayerst, Oncol Res, Pearl River, NY USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 780 BP 3810S EP 3810S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800771 ER PT J AU Wang, H Wang, S Wang, Z Li, M Nan, L Tomaszewski, JE Rhie, JK Zhang, R Hill, DL AF Wang, H Wang, S Wang, Z Li, M Nan, L Tomaszewski, JE Rhie, JK Zhang, R Hill, DL TI Pre-clinical in vitro and in vivo studies with epothilone D, a novel tubulin stabilizing anti-cancer agent. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. NIH, Toxicol & Pharmacol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 781 BP 3810S EP 3811S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800772 ER PT J AU Jung, Y Isaacs, J Neckers, L AF Jung, Y Isaacs, J Neckers, L TI Microtubule-depolymerizing agents induce HIF-1 alpha via NF-kappa B activation. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 783 BP 3811S EP 3811S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800774 ER PT J AU Shilkaitis, A Aldaz, C Steele, VE Lubet, R Grubbs, C Christov, K AF Shilkaitis, A Aldaz, C Steele, VE Lubet, R Grubbs, C Christov, K TI Terminal replicative senescence, a potential target for breast cancer chemoprevention strategies. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Illinois, Chicago, IL USA. Univ Texas, MD Anderson Canc Ctr, Smithville, TX USA. NCI, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 790 BP 3812S EP 3812S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800781 ER PT J AU Kavanaugh, C Couldrey, C Green, J AF Kavanaugh, C Couldrey, C Green, J TI Initiating oncogenic pathway determines whether cycloxygenase-2 is a target for therapy in transgenic mouse models of mammary cancer: lack of correlation between COX-2 expression and estrogen receptor alpha status. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 796 BP 3813S EP 3813S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800787 ER PT J AU Dowlati, A Payne, J Robertson, K Ksenich, P Makkar, V Overmoyer, B Jacobberger, J Whitacre, C Cooper, B Lazarus, H Gerson, S Murgo, A Remick, S AF Dowlati, A Payne, J Robertson, K Ksenich, P Makkar, V Overmoyer, B Jacobberger, J Whitacre, C Cooper, B Lazarus, H Gerson, S Murgo, A Remick, S TI Phase I trial of combination bryostatin-1 and vincristine in B-cell malignancies: Final report. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Hosp Cleveland, Dev Therapeut Program, Ctr Comprehens Canc, Cleveland, OH USA. Case Western Reserve Univ, Dev Therapeut Program, Ctr Comprehens Canc, Cleveland, OH USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 800 BP 3814S EP 3814S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800791 ER PT J AU Marshall, JL Rizvi, N Fox, E Figueira, M Arlen, P Gulley, J Tsang, K Schlom, J AF Marshall, JL Rizvi, N Fox, E Figueira, M Arlen, P Gulley, J Tsang, K Schlom, J TI A phase I study of sequential vaccinations with fowlpox-CEA (6D)-TRICOM (B7/ICAM/LFA3) alone, and in combination with vaccinia-CEA (6D)-TRICOM and GM-CSF in patients with CEA expressing carcinomas. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Vincent T Lombardi Canc Res Ctr, Washington, DC USA. NCI, CCR, Tumor Immunol & Biol Lab, Bethesda, MD USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 798 BP 3814S EP 3814S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800789 ER PT J AU Staudt, LM AF Staudt, LM TI Molecular diagnosis of lymphoma by gene expression profiling reveals novel molecular targets. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA P804 BP 3815S EP 3815S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800795 ER PT J AU Trent, JM AF Trent, JM TI Classification and predictive modeling using microarrays. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA P805A BP 3815S EP 3815S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800797 ER PT J AU Mills, G Lu, Y Fang, X Wang, H Eder, A Mao, M Swaby, R Cheng, KW Siminovitch, K Kohn, EC Stokoe, D Kuo, WL Jaffe, R Gray, J AF Mills, G Lu, Y Fang, X Wang, H Eder, A Mao, M Swaby, R Cheng, KW Siminovitch, K Kohn, EC Stokoe, D Kuo, WL Jaffe, R Gray, J TI Role of genetic abnormalities of PTEN and the phosphatidylinositol 3 kinase pathway in breast and ovarian cancer tumorigenesis, prognosis and therapy. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Toronto, Toronto, ON, Canada. NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA P820 BP 3820S EP 3821S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800813 ER PT J AU Amundson, SA Fornace, AJ AF Amundson, SA Fornace, AJ TI Exploiting cDNA arrays to understand radiation targets in human cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA W827 BP 3822S EP 3823S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800820 ER PT J AU Tofilon, PJ AF Tofilon, PJ TI Signaling pathways as targets for radiosensitization. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA W826 BP 3822S EP 3822S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800819 ER PT J AU Dancey, J AF Dancey, J TI Mammalian target of rapamycin (mTOR) as a target for cancer therapeutic development. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Natl Canc Inst, Rockville, MD USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA W830 BP 3823S EP 3824S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800823 ER PT J AU Biesecker, BB AF Biesecker, BB TI Goals of genetic counseling SO CLINICAL GENETICS LA English DT Review DE genetic counseling; goals of counseling; review of genetic counseling; specific aims of genetic counseling ID NONDIRECTIVENESS; SATISFACTION; INFORMATION; ATTITUDES; OUTCOMES; ISSUES; RECALL AB The goals of genetic counseling have differed over the past three decades. Two schools of thought are prominent in reviewing past literature. One upholds the goal of preventing birth defects and genetic disorders while the other promotes a goal of improved psychological well-being in client adaptation to a genetic condition or risk. Both types of goals emphasize that clients should make their own reproductive decisions; however. the former relies on clients making decisions that will reduce the impact of genetic disorders. The differences in the types of goals may be due to the training and orientation of genetics health care providers. socio-cultural views, or priorities of health care settings. Regardless. there are ample reasons to dismiss the prevention of birth defects as a goal. This mini-review recommends use of genetic counseling sub-specialties as a framework for considering different client needs and thus different counseling goals and specific aims in the reproductive, pediatric/adult. and common disease settings. Given the extent of new genetic information, technologies. and the need to evaluate genetic counseling practice. genetics health care providers should work toward arriving at consensus on the goals of genetic counseling, and in doing so., the needs of clients should be considered. C1 NHGRI, NIH, Bethesda, MD 20897 USA. RP Biesecker, BB (reprint author), NHGRI, NIH, 10 Ctr Dr MSC 1852,Bldg 10,Room 10C101, Bethesda, MD 20897 USA. NR 47 TC 78 Z9 80 U1 1 U2 16 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD NOV PY 2001 VL 60 IS 5 BP 323 EP 330 DI 10.1034/j.1399-0004.2001.600501.x PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 497UZ UT WOS:000172475000001 PM 11903329 ER PT J AU Egan, CA Brown, M White, JD Yancey, KB AF Egan, CA Brown, M White, JD Yancey, KB TI Treatment of epidermolysis bullosa acquisita with the humanized anti-Tac mAb daclizumab SO CLINICAL IMMUNOLOGY LA English DT Article DE autoimmunity; bullous disease; therapy ID INTERLEUKIN-2 RECEPTOR; ACUTE REJECTION; SKIN; TRANSPLANTATION; IDENTIFICATION; BLOCKADE; DISEASE; BINDING AB Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease characterized by IgG anti-basement membrane autoantibodies to collagen VII. Since autoantibody formation in EBA patients is thought to be T-cell-dependent, the degree of T cell activation in three patients (all males, ages 33-44 years) was assessed by quantitation of soluble Tac, a fragment of the a-subunit of the high-affinity IL-2 receptor (CD25). Soluble Tac levels in all patients were elevated [highest random values, 2430, 920, and 560 IU/ml (normal range, 112-502)] Based on such findings, these patients were treated with the humanized murine monoclonal anti-Tac antibody daclizumab (1 mg/kg, 6-12 iv treatments at 2- to 4-week intervals). All patients had a significant, rapid, and persistent decrease in lymphocyte CD25 expression. Though a moderate decrease in lymphocyte expression of 7G7, an IL-2 receptor epitope not bound by daclizumab, was noted, stable levels of CD3 cells and in vitro saturation studies indicated that daclizumab effectively bound CD25 and did not promote clearance of such cells from peripheral blood. There were no complications and no patient developed antibodies against daclizumab. While no apparent clinical benefit was seen in two patients with dermolytic disease, one patient with inflammatory EBA had a favorable response. While on daclizumab, this patient stopped prednisone, significantly reduced dapsone, and improved clinically. Furthermore, his disease flared when treatment was stopped, and resumption of daclizumab again effected improvement within 2 weeks. Daclizumab therapy is safe and well tolerated in EBA patients. It may be effective as a corticosteroid sparing agent in patients with inflammatory EBA. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Lab Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Off Canc Complementary & Alternat Med, NIH, Bethesda, MD 20892 USA. RP Egan, CA (reprint author), Beaumont Hosp, Dept Dermatol, Beaumont Rd, Dublin 9, Ireland. NR 18 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD NOV PY 2001 VL 101 IS 2 BP 146 EP 151 DI 10.1006/clim.2001.5113 PG 6 WC Immunology SC Immunology GA 494AJ UT WOS:000172255600004 PM 11683573 ER PT J AU Rompalo, AM Gaydos, CA Shah, N Tennant, M Crotchfelt, KA Madico, G Quinn, TC Daniel, R Shah, KV Gaydos, JC McKee, KT AF Rompalo, AM Gaydos, CA Shah, N Tennant, M Crotchfelt, KA Madico, G Quinn, TC Daniel, R Shah, KV Gaydos, JC McKee, KT TI Evaluation of use of a single intravaginal swab to detect multiple sexually transmitted infections in active-duty military women SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CHLAMYDIA-TRACHOMATIS INFECTION; LIGASE CHAIN-REACTION; NEISSERIA-GONORRHOEAE; VAGINAL SWABS; PCR; DIAGNOSIS; PREVALENCE; SPECIMENS; SAMPLES AB The accuracy and suitability of use of a single intravaginal swab (SIS) for polymerase chain reaction detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and human papillomavirus infection was assessed in a cross-sectional study of 841 active-duty military women. The SIS, compared with standard diagnostic tests, allowed detection of more gonorrhea, more chlamydial infection, and more trichomoniasis. Sensitivity and specificity of SIS detection compared with adjudicated true-positive diagnoses were 95.8% and 97.8%, respectively, for gonorrhea, 94.6% and 99.3% for chlamydial infection, and 92.2% and 98.2% for trichomonal infection. Results with SISs were comparable to those with cervical swabs tested for human papillomavirus. Assay of clinician-collected and self-collected SISs yielded prevalences similar to those of standard diagnostic tests for all sexually transmitted infections. Therefore, the use of SISs is acceptable for the simultaneous diagnosis of multiple sexually transmitted infections and has potential for use as a self-administered diagnostic tool with widespread applicability among women. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. Dept Def Global Emerging Infect Surveillance & Re, Silver Spring, MD USA. Womack Army Med Ctr, Ft Bragg, NC USA. RP Rompalo, AM (reprint author), 1830 E Monument St,Rm 447, Baltimore, MD 21287 USA. RI Gaydos, Charlotte/E-9937-2010 NR 24 TC 44 Z9 44 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2001 VL 33 IS 9 BP 1455 EP 1461 DI 10.1086/322588 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 479PE UT WOS:000171412100002 PM 11568849 ER PT J AU Moscicki, EK AF Moscicki, EK TI Epidemiology of completed and attempted suicide: toward a framework for prevention SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE suicide; attempted suicide; epidemiology; risk factor; prevention ID SAN-DIEGO SUICIDE; RISK-FACTORS; ADOLESCENT SUICIDE; MENTAL-DISORDERS; SEXUAL ORIENTATION; TEENAGE SUICIDE; PANIC DISORDER; YOUTH SUICIDE; PSYCHOLOGICAL AUTOPSY; GENERAL POPULATION AB Suicide is an important public health problem. It is a complex. long-term outcome of mental illness, with multiple. interacting antecedents. This paper reviews descriptive and analytic epidemiologic studios of completed and attempted suicide, discusses the primary sources of epidemiologic data, and describes the major risk factors for completed and attempted suicide. Risk factors are described within a framework that distinguishes between distal and proximal. and individual and environmental antecedents. Organization of our knowledge of risk and protective factors for both completed and attempted suicide provides opportunities to develop and implement life-saving preventive strategies. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIMH, Bethesda, MD 20892 USA. RP Moscicki, EK (reprint author), NIMH, Room 8209,MSC 9663,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 156 TC 145 Z9 148 U1 8 U2 29 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD NOV PY 2001 VL 1 IS 5 BP 310 EP 323 AR PII S1566-2772(01)00032-9 DI 10.1016/S1566-2772(01)00032-9 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529FE UT WOS:000174288700002 ER PT J AU Miller, NH Schwab, DL Sponseller, PD Manolio, TA Pugh, EW Wilson, AP AF Miller, NH Schwab, DL Sponseller, PD Manolio, TA Pugh, EW Wilson, AP TI Characterization of idiopathic scoliosis in a clinically well-defined population SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID GENES; TWINS AB Idiopathic scoliosis is a highly prevalent disorder, familial in nature, with marked clinical variability. The purpose of this study was to characterize idiopathic scoliosis in a large series of families to be used for a genome-wide search. One hundred thirty-one multigenerational families (892 individuals) with at least two affected individuals were studied. Data obtained included curve pattern, treatment, and back pain. Maximum curvature as a continuous variable was evaluated using t tests for dichotomous characteristics and linear correlation for continuous variables. An analysis of familial loading was done. Four hundred forty-four individuals were classified as affected (82% female; 18% male). The right thoracic and left lumbar curves had the highest mean curvature (49 degrees). Mean curve size was greater in individuals with back pain. Back pain was most prevalent in the right thoracic and left lumbar curve pattern. The Pearson correlation coefficient between the number of affected family members and the maximum degree of curvature was 0.16, suggesting that the greater the lateral curvature, the higher the proportion of family members affected with scoliosis. The sample population is consistent with those of previous studies in relation to gender and curve size. Statistically, the familial nature of this disorder is supported. C1 Johns Hopkins Univ, Dept Orthopaed Surg, Baltimore, MD 21287 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Triad Technol Ctr, Ctr Inherited Dis REs, Baltimore, MD USA. NHGRI, Genometr Sect, NIH, Baltimore, MD USA. RP Miller, NH (reprint author), Johns Hopkins Univ, Dept Orthopaed Surg, 601 N Caroline St, Baltimore, MD 21287 USA. RI Wilson, Alexander/C-2320-2009 NR 54 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2001 IS 392 BP 349 EP 357 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 491BA UT WOS:000172087100045 PM 11716406 ER PT J AU Furuta, T Shirai, N Xiao, F Ohashi, K Ishizaki, T AF Furuta, T Shirai, N Xiao, F Ohashi, K Ishizaki, T TI Effect of high-dose lansoprazole on intragastic pH in subjects who are homozygous extensive metabolizers of cytochrome P4502C19 SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID S-MEPHENYTOIN 4'-HYDROXYLATION; GASTRIC-ACID BREAKTHROUGH; PROTON PUMP INHIBITORS; GASTROESOPHAGEAL REFLUX; DUODENAL-ULCER; GENOTYPE STATUS; OMEPRAZOLE; POLYMORPHISM; CYP2C19; JAPANESE AB Backgrounds and Aim: Lansoprazole is mainly metabolized by cytochrome P4502C19 (CYP2C19) in the liver. The effect of lansoprazole is assumed to be insufficient in subjects who are homozygous extensive metabolizers of CYP2C19. This study aimed to examine whether the CYP2C19 genotype status affected the acid-inhibitory effects of lansoprazole and to develop a strategy to overcome this pharmacogenetic problem. Methods: Eighteen Helicobacter pylori-negative healthy volunteers, whose CYP2C19 genotypic status had been assessed, participated in the study. They consisted of 7 subjects who were homozygous extensive metabolizers, 7 subjects who were heterozygous extensive metabolizers, and 4 subjects who were poor metabolizers of CYP2C19, who took a placebo or lansoprazole 30 mg once daily in the morning for 8 days. On day 8 of closing, 24-hour intragastric pH values were recorded. Five of the homozygous extensive metabolizer subjects underwent the 24-hour intragastric pH monitoring on day 8 of dosing of lansoprazole 30 mg 4 times daily. Results: When lansoprazole 30 mg was given once daily, the mean 24-hour intragastric pH values in the subjects who were homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers were 4.5, 4.9, and 5.5, respectively (P < .005). On day 8 of dosing of lansoprazole 30 mg 4 times daily in subjects who were homozygous extensive metabolizers, the mean 24-hour intragastric pH value was 7.4. Conclusion: The effect of lansoprazole on intragastric pH depended significantly on CYP2C19 genotype status. Complete acid inhibition could be achieved by the frequent administration of lansoprazole (eg, 30 mg 4 times daily) in subjects who were homozygous extensive metabolizers. A genotyping test of CYP2C19 status appears useful for prescribing an optimal dosing scheme of lansoprazole. C1 Hamamatsu Univ Sch Med, Dept Med 1, Hamamatsu, Shizuoka 43131, Japan. Hamamatsu Univ Sch Med, Dept Clin Pharmacol, Hamamatsu, Shizuoka 43131, Japan. Kumamoto Univ, Grad Sch Clin Pharm, Dept Pharmacol & Therapeut, Kumamoto, Japan. RP Furuta, T (reprint author), NCI, Mol Pharmacol Lab, NIH, 37 Convent Dr,Bldg 37,Room 4D15, Bethesda, MD 20892 USA. EM furutat@mail.nih.gov NR 33 TC 79 Z9 85 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2001 VL 70 IS 5 BP 484 EP 492 DI 10.1067/mcp.2001.119721 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 500KH UT WOS:000172625900011 PM 11719736 ER PT J AU Pham, DL AF Pham, DL TI Spatial models for fuzzy clustering SO COMPUTER VISION AND IMAGE UNDERSTANDING LA English DT Article DE fuzzy clustering; fuzzy c-means; image segmentation; Markov random fields; cross-validation ID IMAGE SEGMENTATION; RESTORATION; ALGORITHM AB A novel approach to fuzzy clustering for image segmentation is described. The fuzzy C-means objective function is generalized to include a spatial penalty on the membership functions. The penalty term leads to an iterative algorithm that is only slightly different from the original fuzzy C-means algorithm and allows the estimation of spatially smooth membership functions. To determine the strength of the penalty function, a criterion based on cross-validation is employed. The new algorithm is applied to simulated and real magnetic resonance images and is shown to be more robust to noise and other artifacts than competing approaches. (C) 2001 Elsevier Science (USA). C1 NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Pham, DL (reprint author), NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 24 TC 185 Z9 204 U1 0 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1077-3142 J9 COMPUT VIS IMAGE UND JI Comput. Vis. Image Underst. PD NOV PY 2001 VL 84 IS 2 BP 285 EP 297 DI 10.1006/cviu.2001.0951 PG 13 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 527PR UT WOS:000174195400005 ER PT J AU Garnett, N Gipson, C AF Garnett, N Gipson, C TI Suggestions to bring electronic protocol system into compliance SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Letter C1 NIH, Off Lab Anim Welf, Bethesda, MD 20892 USA. USDA, APHIS, Washington, DC 20250 USA. RP Garnett, N (reprint author), NIH, Off Lab Anim Welf, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD NOV PY 2001 VL 40 IS 6 BP 8 EP 8 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 494XF UT WOS:000172310600003 PM 11757526 ER PT J AU Piatigorsky, J AF Piatigorsky, J TI Enigma of the abundant water-soluble cytoplasmic proteins of the cornea - The "refracton" hypothesis SO CORNEA LA English DT Article DE corneal proteins; crystallins; gene expression; refracton ID RETINOL-BINDING PROTEIN; ALDEHYDE DEHYDROGENASE; TRANSGENIC MICE; EYE LENS; GENE-EXPRESSION; BOVINE CORNEA; CUBOMEDUSAN JELLYFISH; STRUCTURAL PROTEIN; ULTRAVIOLET FILTER; CRYSTALLIN GENE AB It is accepted that the taxon-specific, multifunctional crystallins. (small heat-shock proteins and enzymes) serve structural roles contributing to the transparent and refractive properties of the lens. The transparent cornea also accumulates unexpectedly high proportions of taxon-specific, multifunctional proteins particularly, but not only, in the epithelium. For example, aldehyde dehydrogenase 3 (ALDH3) is the main water-soluble protein in corneal epithelial cells of most mammals (but ALDH1 predominates in the rabbit), whereas gelsolin predominates in the zebrafish corneal epithelium. Moreover, some invertebrates (e.g., squid and scallop) accumulate proteins in their corneas that are similar to their lens crystallins. Pax-6, among other transcription factors, is implicated in development and tissue-specific gene expression of the lens and cornea. Environmental factors appear to influence gene expression in the cornea, but not the lens. Although no direct proof exists, the diverse, abundant corneal proteins may have evolved a crystallinlike role, in addition to their enzymatic or cytoskeletal functions, by a gene sharing mechanism similar to the lens crystallins. Consequently, it is proposed that the cornea and lens be considered as a single refractive unit, called here the "refracton," to emphasize their similarities and common function. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, 6 Ctr Dr,Bldg 6,Room 201, Bethesda, MD 20892 USA. NR 66 TC 74 Z9 75 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 2001 VL 20 IS 8 BP 853 EP 858 DI 10.1097/00003226-200111000-00015 PG 6 WC Ophthalmology SC Ophthalmology GA 488ZB UT WOS:000171965900014 PM 11685065 ER PT J AU Blum, A Cannon, RO AF Blum, A Cannon, RO TI L-Arginine for the prevention and treatment of coronary artery disease SO CORONARY ARTERY DISEASE LA English DT Review DE L-arginine; nitric oxide; endothelium; atherosclerosis ID NITRIC-OXIDE SYNTHASE; ORAL L-ARGININE; ENDOTHELIUM-DEPENDENT VASODILATION; HUMAN MONOCYTE ADHESION; STABLE ANGINA-PECTORIS; DIETARY L-ARGININE; HYPERCHOLESTEROLEMIC RABBITS; ASYMMETRIC DIMETHYLARGININE; RELAXING FACTOR; DYSFUNCTION C1 Poriya Govt Hosp, Dept Internal Med, IL-15208 Lower Galilee, Israel. NIH, Cardiol Branch, Bethesda, MD 20892 USA. RP Blum, A (reprint author), Poriya Govt Hosp, Dept Internal Med, IL-15208 Lower Galilee, Israel. NR 56 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD NOV PY 2001 VL 12 IS 7 BP 535 EP 539 DI 10.1097/00019501-200111000-00002 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 495CL UT WOS:000172322600002 PM 11714992 ER PT J AU Karp, JE Kaufmann, SH Adjei, AA Lancet, JE Wright, JJ End, DW AF Karp, JE Kaufmann, SH Adjei, AA Lancet, JE Wright, JJ End, DW TI Current status of clinical trials of farnesyltransferase inhibitors SO CURRENT OPINION IN ONCOLOGY LA English DT Review ID FARNESYL TRANSFERASE INHIBITORS; PROTEIN TRANSFERASE; IN-VITRO; ANTITUMOR-ACTIVITY; GROWTH-INHIBITION; PHASE-I; RAS; TARGET; CELLS; RESISTANCE AB Farnesyltransferase inhibitors represent a new class of agents that target signal transduction pathways responsible for the proliferation and survival of diverse malignant cell types. Although these agents were developed to prevent a processing step necessary for membrane attachment and maturation of Ras proteins, recent studies suggest that farnesyltransferase inhibitors block the farnesylation of additional cellular polypeptides, thereby exerting antitumor effects independent of the presence of activating ras gene mutations. Clinical trials of two farnesyltransferase inhibitors-the tricyclic SCH66336 and the methylquinolone R115777-as single agents have demonstrated disease stabilization or objective responses in 10 to 15% of patients with refractory malignancies. Combinations of farnesyltransferase inhibitors with cytotoxic chemotherapies are yielding complete and partial responses in patients with advanced solid tumors. A phase I trial of R115777 in refractory and relapsed acute leukemias induced responses in 8 (32%) of 25 patients with acute myelogenous leukemia (including two complete remissions) and in two of three with chronic myelogenous leukemia in blast crisis. In patients with solid tumors, accessible normal tissues such as peripheral blood lymphocytes or, perhaps more germane to epithelial malignancies, buccal mucosa have provided surrogate tissues that allow confirmation that farnesyltransferase is inhibited in vivo at clinically achievable drug doses. In conjunction with the R115777 acute leukemia trial, serial measurements provided evidence of farnesyltransferase enzyme inhibition, interference with farnesyltransferase function (ie, protein processing), and blockade of signal transduction pathways in leukemic bone marrow cells. Preclinical studies of farnesyltransferase inhibitor resistance and clinical trials of farnesyltransferase inhibitors in combination with other agents currently are in progress. Curr Opin Oncol 2001, 13:470-476 (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Mayo Clin, Dept Oncol, Rochester, MN USA. Univ Rochester, Ctr Canc, Rochester, NY USA. NCI, Bethesda, MD 20892 USA. Janssen Res Fdn, Titusville, NJ USA. RP Karp, JE (reprint author), Univ Maryland, Greenebaum Canc Ctr, 22 S Greene St,Room S9D07, Baltimore, MD 21201 USA. FU NCI NIH HHS [U01 CA669854] NR 53 TC 98 Z9 103 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD NOV PY 2001 VL 13 IS 6 BP 470 EP 476 DI 10.1097/00001622-200111000-00009 PG 7 WC Oncology SC Oncology GA 487XR UT WOS:000171905100009 PM 11673687 ER PT J AU Leitner, WW Hammerl, P Thalhamer, J AF Leitner, WW Hammerl, P Thalhamer, J TI Nucleic acid for the treatment of cancer: Genetic vaccines and DNA adjuvants SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID CYTOTOXIC-T-LYMPHOCYTE; COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; B-CELL LYMPHOMA; ANTIGEN-PRESENTING CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; MYCOBACTERIUM-BOVIS BCG; MARROW-DERIVED CELLS; TOLL-LIKE RECEPTOR-2; PLASMID DNA AB Despite some interesting pilot experiments more than a century ago, nucleic acid has only recently been added to the list of agents used for the prevention and therapy of cancer. Two distinct features of nucleic acids are used for this purpose: in DNA and RNA vaccines, genetic information for pathogen- or tumor-derived antigens is delivered to the host who then produces the encoded antigen and initiates an immune response. In DNA adjuvants, immunostimulatory sequences (CpG motifs) present in DNA of bacterial origin are used. Such sequences are delivered in the form of oligonucleotides or within the sequence of DNA vaccine. In addition, CpG oligonucleotides by themselves have successfully been used to stimulate the immune system in an antigen-independent manner for the treatment of experimental tumors. DNA and RNA vaccines for the treatment and prevention of cancer and other diseases suffer from two some shortcomings: insufficient immunogenicity and - in the case of RNA - low stability. A variety of strategies are being explored to improve the efficacy of nucleic acid vaccines (genetic vaccines) especially for self-antigens in the case of cancer. Among the most recent improvements are self-replicating RNA vaccines and replicase-based DNA-vaccines in which antigen expression is under the control of an alphaviral replicase. Despite highly promising results in many animal tumor models the efficacy of nucleic acid vaccines and adjuvants in the clinic remains to be seen. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Salzburg Univ, Immunol Grp, Inst Chem & Biochem, A-5020 Salzburg, Austria. RP Leitner, WW (reprint author), NCI, Surg Branch, NIH, Room 2B46,Bldg 10, Bethesda, MD 20892 USA. RI Leitner, Wolfgang/F-5741-2011; Thalhamer, Josef/E-5787-2011 OI Leitner, Wolfgang/0000-0003-3125-5922; Thalhamer, Josef/0000-0003-2285-6400 NR 203 TC 27 Z9 27 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD NOV PY 2001 VL 7 IS 16 BP 1641 EP 1667 DI 10.2174/1381612013397249 PG 27 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 486QC UT WOS:000171827600007 PM 11562304 ER PT J AU Roy, KK Sausville, EA AF Roy, KK Sausville, EA TI Early development of cyclin dependent kinase modulators SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID RNA-POLYMERASE-II; BREAST-CARCINOMA CELLS; DNA-DAMAGE CHECKPOINT; NATURAL PRODUCT HYMENIALDISINE; CDK-ACTIVATING KINASE; ACTIVITY IN-VIVO; FACTOR P-TEFB; PROTEIN-KINASE; SELECTIVE INHIBITOR; TUMOR-SUPPRESSOR AB The protein kinase family presents remarkable opportunities for drug discovery and development targeting mainly to the ATP binding cleft. Cyclin-dependent kinases CDKs control the cell division in by controlling its sub phases. The regulation of CDKs is altered in a number of tumor types, and therefore CDKs are a particularly attractive target group of kinases with reference to proliferative disorders including cancer, but also extending to graft stenosis, and autoimmune disorders. Screening of chemical modulators of CDKs that modulate aberrant CDK activity might be beneficial for cancer therapy by directly inhibiting kinase activity, or influencing cell cycle "checkpoint" function, which is mediated through effects of exogenous cellular regulators of CDK activity. In this regard small molecule modulators such as flavopiridol and UCN-01 are in early clinical trials. Other more selective modulators of CDK function are being actively sought, and initial results with flavopiridol analogs, indirubins, paullones, and purine-based inhibitors will be considered. C1 NCI, Clin Trials Unit, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Roy, KK (reprint author), NCI, Clin Trials Unit, Dev Therapeut Program, Div Canc Treatment & Diag, 10 Ctr Dr,Bldg 10,Room 6N 113, Bethesda, MD 20892 USA. NR 190 TC 19 Z9 19 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD NOV PY 2001 VL 7 IS 16 BP 1669 EP 1687 DI 10.2174/1381612013397230 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 486QC UT WOS:000171827600008 PM 11562305 ER PT J AU Frank, S Ebert, AD AF Frank, S Ebert, AD TI License to kill tumors: How much hope is justified for trail? SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID APOPTOSIS-INDUCING LIGAND; NF-KAPPA-B; DOMAIN-CONTAINING PROTEIN; FADD-DEPENDENT APOPTOSIS; NECROSIS-FACTOR-ALPHA; HUMAN-MELANOMA CELLS; DEATH RECEPTOR GENE; DECOY RECEPTORS; TNF-ALPHA; NK CELLS AB In 1995, a new cytokine termed TRAIL (tumor necrosis factor - related apoptosis-inducing ligand) was discovered and demonstrated to selectively induce programmed cell death in transformed cell lines. Preclinical cytotoxicity studies in mice and nonhuman primates have produced promising results by demonstrating that TRAIL exerts potent tumoricidal activity but lacks severe toxicity towards normal tissues making it a potentially ideal candidate for cancer therapy. This article reviews aspects of our current understanding of TRAIL signaling pathways and summarizes how this knowledge is currently being translated into TRAIL-based tumor selective therapeutic strategies. C1 NINCDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Tumor Growth Factor Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD USA. Free Univ Berlin, Dept Obstet & Gynecol, D-1000 Berlin, Germany. RP Frank, S (reprint author), NINCDS, Biochem Sect, Surg Neurol Branch, NIH, Bldg 10,Room 4N258, Bethesda, MD 20892 USA. NR 136 TC 9 Z9 10 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD NOV PY 2001 VL 7 IS 16 BP 1689 EP 1701 DI 10.2174/1381612013397212 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 486QC UT WOS:000171827600009 PM 11562306 ER PT J AU Bergmann-Leitner, ES AF Bergmann-Leitner, ES TI The novel approaches for the development of anti-cancer drugs - Preface SO CURRENT PHARMACEUTICAL DESIGN LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Bergmann-Leitner, ES (reprint author), Walter Reed Army Inst Res, Dept Immunol, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. RI Bergmann-Leitner, Elke/B-3548-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD NOV PY 2001 VL 7 IS 16 BP U2 EP U3 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 486QC UT WOS:000171827600001 ER PT J AU Poggi, MM Coleman, CN Mitchell, JB AF Poggi, MM Coleman, CN Mitchell, JB TI Sensitizers and protectors of radiation and chemotherapy SO CURRENT PROBLEMS IN CANCER LA English DT Review ID PHASE-I TRIAL; HYPOXIC-CELL RADIOSENSITIZER; THERAPY ONCOLOGY GROUP; LOCALLY ADVANCED HEAD; TUMOR BLOOD-FLOW; ADVANCED PROSTATE-CANCER; HAMSTER OVARY CELLS; HIGH-GRADE GLIOMAS; INDUCED DNA DAMAGE; ELECTRON-PARAMAGNETIC-RESONANCE C1 NCI, Radiat Oncol Sci Program, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Poggi, MM (reprint author), NCI, Radiat Oncol Sci Program, Radiat Biol Branch, Bethesda, MD 20892 USA. NR 452 TC 16 Z9 17 U1 0 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0147-0272 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD NOV-DEC PY 2001 VL 25 IS 6 BP 334 EP 411 DI 10.1067/mcn.2001.120122 PG 78 WC Oncology SC Oncology GA 503VM UT WOS:000172822200001 PM 11740469 ER PT J AU Ardekani, AM Herman, EH Sistare, FD Liotta, LA Petricoin, EF AF Ardekani, AM Herman, EH Sistare, FD Liotta, LA Petricoin, EF TI Molecular profiling of cancer and drug-induced toxicity using new proteomic technologies SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT Workshop on Adverse Drug Events in Pediatrics CY APR 09-10, 2001 CL ROCKVILLE, MD DE proteomics; toxicity; cancer; SELDI-TOF; microdissection ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PATTERNS; POLYACRYLAMIDE-GEL ELECTROPHORESIS; TRANSITIONAL-CELL CARCINOMAS; PROSTATE-SPECIFIC ANTIGEN; ACID-BINDING PROTEIN; LOW-FEMTOMOLE LEVEL; MASS-SPECTROMETRY; MESSENGER-RNA; EPITHELIAL-CELLS AB Background: Completion of the mapping of the human genome has brought the field of research in biological sciences into a new dawn of discovery. Within this postgenomics era in science, proteomic technologies are positioned to play a major role in discovery of new biomarkers for early detection of diseases and drug-induced toxicity, new molecular targets for therapy, and new end points for therapeutic efficacy and toxicity. Objective: Development of patient-specific targeted therapeutics with reduced toxicity and increased efficacy using cells or sera from patients with disease. Methods: New proteomic technologies such as laser capture microscopy are providing rapid, easy access to the purified, diseased human cells from tissue specimens that previously has not been possible. Due to limited availability of patient material, highly sensitive mass spectrometric techniques such as surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) are used to complement 2-dimensional gel electrophoresis for multiparametric protein characterization. Results: The use of high-throughput SELDI-TOF protein pattern generation techniques should prove valuable for new molecular classification of human tumors, disease stages, and drug-induced toxicity. The use of newly developed high-density protein arrays, antibody arrays, and small molecular arrays in conjunction with laser capture microscopy could have a substantial impact on proteomic profiling of human tumors and human tissues affected in response to drug treatments. SELDI-TOF and laser capture microscopy technologies in conjunction with new bioinformatic software will be powerful tools in the near future for identifying protein fingerprints in cells or sera of patients to predict the outcomes of therapies for any diagnosed disease. Conclusions: The application of all new proteomic technologies should enhance our efforts in designing rational drug therapy strategies that are based on an individual patient's molecular profiling of cellular proteins in the disease state and can identify proteomic fingerprints associated with drug-induced toxicity directly in sera samples. This should provide us with the detailed knowledge necessary to develop novel therapeutics for the treatment of diseases and/or detection of diseases and toxicity at an early stage. C1 NCI, Div Therapeut Prod, US FDA, Clin Proteom Program,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Laurel, MD USA. RP Petricoin, EF (reprint author), NCI, Div Therapeut Prod, US FDA, Clin Proteom Program,Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29A,Room 2B02, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 73 TC 7 Z9 7 U1 1 U2 2 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD NOV PY 2001 VL 62 IS 11 BP 803 EP 819 DI 10.1016/S0011-393X(01)80087-4 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 501VN UT WOS:000172706900007 ER PT J AU Roederer, M AF Roederer, M TI Spectral compensation for flow cytometry: Visualization artifacts, limitations, and caveats SO CYTOMETRY LA English DT Article DE flow cytometry; data analysis; compensation; multicolor immunophenotyping ID SENSITIVITY; COLOR AB Background: In multicolor flow cytometric analysis, compensation for spectral overlap is nearly always necessary. For the most part, such compensation has been relatively simple, producing the desired rectilinear distributions. However, in the realm of multicolor analysis, visualization of compensated often results in unexpected distributions, principally the appearance of a large number of events on the axis, and even more disconcerting, an inability to bring the extent of compensated data down to "autofluorescence" levels. Materials and Methods: A mathematical model of detector measurements with variable photon intensities, spillover parameters, measurement errors, and data storage characteristics was used to illustrate sources of apparent error in compensated data. Immunofluorescently stained cells were collected under conditions of limiting light collection and high spillover between detectors to confirm aspects of the model. Results: Photon-counting statistics contribute a nonlinear error to compensated parameters. Measurement errors and log-scale binning error contribute linear errors to compensated parameters. These errors are most apparent with the use of red or far-red fluorochromes (where the emitted light is at low intensity) and with large spillover between detectors. Such errors can lead to data visualization artifacts that can easily lead to incorrect conclusions about data, and account for the apparent "undercompensation" previously described for multicolor staining. Conclusions: There are inescapable errors arising from imperfect measurements, photon-counting statistics, and even data storage methods that contribute both linearly and nonlinearly to a "spreading" of a properly compensated autofluorescence distribution. This phenomenon precludes the use of "quadrant" statistics or gates to analyze affected data; it also precludes visual adjustment of compensation. Most importantly, it is impossible to properly compensate data Using standard visual graphical interfaces (histograms or dot plots). Computer-assisted compensation is required, as well as careful gating and experimental design to determine the distinction between positive and negative events. Finally, the use of special staining controls that employ all reagents except for the one of interest (termed fluorescence minus one, or "FMO" controls) becomes necessary to accurately identify expressing cells in the fully stained sample, Cytometry 45: 194 - 205, 2001. (C) 2001 Wiley-Liss, Inc. C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIH, Vaccine Res Ctr, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. RI Roederer, Mario/G-1887-2011 NR 13 TC 274 Z9 283 U1 4 U2 21 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD NOV 1 PY 2001 VL 45 IS 3 BP 194 EP 205 DI 10.1002/1097-0320(20011101)45:3<194::AID-CYTO1163>3.0.CO;2-C PG 12 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 489ZF UT WOS:000172022600005 PM 11746088 ER PT J AU Belting, HG Hauptmann, G Meyer, D Abdelliah-Seyfried, S Chitnis, A Eschbach, C Soll, I Thisse, C Thisse, B Artinger, KB Lunde, K Driever, W AF Belting, HG Hauptmann, G Meyer, D Abdelliah-Seyfried, S Chitnis, A Eschbach, C Soll, I Thisse, C Thisse, B Artinger, KB Lunde, K Driever, W TI spiel ohne grenzen/pou2 is required during establishment of the zebrafish midbrain-hindbrain boundary organizer SO DEVELOPMENT LA English DT Article DE hindbrain; MHB; midbrain; isthmus; engrailed; fgf8; gbx2; otx2; pax2.1; spg; wnt1; POU domain; Danio rerio ID EMBRYONIC BRAIN; MID/HINDBRAIN ORGANIZER; ISTHMIC ORGANIZER; OTX2 EXPRESSION; CHICK-EMBRYO; NEURAL PLATE; MOUSE-BRAIN; GENE; FGF8; MUTANT AB The vertebrate midbrain-hindbrain boundary (MHB) organizes patterning and neuronal differentiation in the midbrain and anterior hindbrain. Formation of this organizing center involves multiple steps, including positioning of the MHB within the neural plate, establishment of the organizer and maintenance of its regional identity and signaling activities. Juxtaposition of the Otx2 and Gbx2 expression domains positions the MHB. How the positional information is translated into activation of Pax2, Wnt1 and Fgf8 expression during MHB establishment remains unclear. In zebrafish spiel ohne grenzen (spg) mutants, the MHB is not established, neither isthmus nor cerebellum form, the midbrain is reduced in size and patterning abnormalities develop within the hindbrain. In spg mutants, despite apparently normal expression of otx2, gbx1. and fgf8 during late gastrula stages, the initial expression of pax2.1, wnt1 and eng2, as well as later expression of fgf8 in the MHB primordium are reduced. We show that spg mutants have lesions in pou2, which encodes a POU-domain transcription factor. Maternal pou2 transcripts are distributed evenly in the blastula, and zygotic expression domains include the midbrain and hindbrain primordia during late gastrulation. Microinjection of pou2 mi can rescue pax2.1 and wnt1 expression in the MHB of spg/pou2 mutants without inducing ectopic expression. This indicates an essential but permissive role for pou2 during MHB establishment. pou2 is expressed normally in noi/pax2.1 and ace/fgf8 zebrafish mutants, which also form no MHB. Thus, expression of pou2 does not depend on fgf8 and pax2.1. Our data suggest that pou2 is required for the establishment of the normal expression domains of wntl and pax2.1 in the MHB primordium. C1 Univ Freiburg, Inst Biol 1, D-79104 Freiburg, Germany. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. NICHHD, Unit Vertebrate Neural Dev, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. IGBMC, F-67404 Illkirch Graffenstaden, France. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Driever, W (reprint author), Univ Freiburg, Inst Biol 1, Hauptstr 1, D-79104 Freiburg, Germany. FU NICHD NIH HHS [F32 HD008209, F32 HD008209-04] NR 65 TC 72 Z9 74 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 2001 VL 128 IS 21 BP 4165 EP 4176 PG 12 WC Developmental Biology SC Developmental Biology GA 496HF UT WOS:000172389600006 PM 11684654 ER PT J AU Coppola, V Kucera, J Palko, ME Martinez-De Velasco, J Lyons, WE Fritzsch, B Tessarollo, L AF Coppola, V Kucera, J Palko, ME Martinez-De Velasco, J Lyons, WE Fritzsch, B Tessarollo, L TI Dissection of NT3 functions in vivo by gene replacement strategy SO DEVELOPMENT LA English DT Article DE NT3; BDNF; TrkA; TrkB; TrkC; DRG; cochlea; sensory neurons; mouse ID NERVE GROWTH-FACTOR; MUSCLE SENSORY NEURONS; DORSAL-ROOT-GANGLIA; NEUROTROPHIC FACTOR; SIGNAL-TRANSDUCTION; MESSENGER-RNA; INNER-EAR; IN-VIVO; TARGET INNERVATION; PRECURSOR CELLS AB The development of the peripheral nervous system is governed in part by a family of neurotrophic factors that signal through Trk tyrosine kinase receptors. Neurotrophin 3 (NT3) ablation in mice causes a more severe neuronal phenotype than deletion of its receptor TrkC, suggesting that NT3 acts also through other non-preferred Trk receptors. To study the role of low-affinity ligand receptor interactions in vivo, we have replaced the Nt3 gene with the gene for brain-derived neurotrophic factor (BDNF), a TrkB ligand. As in NT3 and TrkC null mice, the proprioception system of these mutants failed to assemble. However, sensory fiber projections in the embryonic spinal cord suggest chemotropic effects of BDNF in vivo. In the dorsal root ganglia, the developmental dynamic of neuron numbers demonstrates that NT3 is required for activation of TrkB during neurogenesis and that TrkA is required during target tissue innervation. In the inner ear, the ectopic BDNF rescued the severe neuronal deficits caused by NT3 absence, indicating that TrkB and TrkC activate equivalent pathways to promote survival of cochlear neurons. However, specific increased innervation densities suggest unique functions for BDNF and NT3 beyond promoting neuronal survival. This mouse model has allowed the dissection of specific spatiotemporal Trk receptor activation by NT3. Our analysis provides examples of how development can be orchestrated by complex high- and low-affinity interactions between ligand and receptor families. C1 NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. RP Tessarollo, L (reprint author), NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA. RI Coppola, Vincenzo/E-2917-2011; OI Coppola, Vincenzo/0000-0001-6163-1779; Fritzsch, Bernd/0000-0002-4882-8398 FU NIDCD NIH HHS [2 P01 DC00215] NR 61 TC 54 Z9 57 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 2001 VL 128 IS 21 BP 4315 EP 4327 PG 13 WC Developmental Biology SC Developmental Biology GA 496HF UT WOS:000172389600018 PM 11684666 ER PT J AU Ahn, K Mishina, Y Hanks, MC Behringer, RR Crenshaw, EB AF Ahn, K Mishina, Y Hanks, MC Behringer, RR Crenshaw, EB TI BMPR-IA signaling is required for the formation of the apical ectodermal ridge and dorsal-ventral patterning of the limb SO DEVELOPMENT LA English DT Article DE apical ectodermal ridge; bone morphogenetic protein receptor; dorsal-ventral patterning; engrailed 1; limb development; loxP/cre conditional knockout; mouse ID DEVELOPING CHICK LIMB; NAIL-PATELLA SYNDROME; VERTEBRATE LIMB; SONIC-HEDGEHOG; TARGETED MUTAGENESIS; POLARIZING ACTIVITY; MOUSE; EXPRESSION; NOGGIN; GENE AB We demonstrate that signaling via the bone morphogenetic protein receptor IA (BMPR-IA) is required to establish two of the three cardinal axes of the limb: the proximal-distal axis and the dorsal-ventral axis. We generated a conditional knockout of the gene encoding BMPR-IA (Bmpr) that disrupted BMP signaling in the limb ectoderm. In the most severely affected embryos, this conditional mutation resulted in gross malformations of the limbs with complete agenesis of the hindlimbs. The proximal-distal axis is specified by the apical ectodermal ridge (AER), which forms from limb ectoderm at the distal tip of the embryonic limb bud. Analyses of the expression of molecular markers, such as Fgf8, demonstrate that formation of the AER was disrupted in the Bmpr mutants. Along the dorsal/ventral axis, loss of engrailed 1 (En1) expression in the non-ridge ectoderm of the mutants resulted in a dorsal transformation of the ventral limb structures. The expression pattern of Bmp4 and Bmp7 suggest that these growth factors play an instructive role in specifying dorsoventral pattern in the limb. This study demonstrates that BMPR-IA signaling plays a crucial role in AER formation and in the establishment of the dorsal/ventral patterning during limb development. C1 Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Procter & Gamble Pharmaceut, Mason, OH USA. RP Crenshaw, EB (reprint author), Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 USA. NR 60 TC 171 Z9 177 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 2001 VL 128 IS 22 BP 4449 EP 4461 PG 13 WC Developmental Biology SC Developmental Biology GA 499FC UT WOS:000172559500006 PM 11714671 ER PT J AU Gallo-Hendrikx, E Murray, SA Vonderhaar, BK Xiao, ZXJ AF Gallo-Hendrikx, E Murray, SA Vonderhaar, BK Xiao, ZXJ TI Vanadate disrupts mammary gland development in whole organ culture SO DEVELOPMENTAL DYNAMICS LA English DT Article DE vanadate; protein tyrosine phosphatases; development; mammary gland; whole organ culture ID PROTEIN-TYROSINE PHOSPHATASES; CASEIN-GENE-EXPRESSION; PROGRAMMED CELL-DEATH; HUMAN-BREAST-CANCER; EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX; VANADIUM COMPOUNDS; GROWTH-HORMONE; DNA-SYNTHESIS; NEU ONCOGENE AB Protein tyrosine kinases and phosphatases are signaling molecules involved in all aspects of development, including proliferation, differentiation, and apoptosis. How disruption of protein tyrosine phosphatase affects mammary gland development is not entirely clear. We examined the effects of sodium vanadate, which is known to primarily inhibit tyrosine phosphatases, in mouse mammary gland development in whole organ culture. Mammary epithelial differentiation was effectively inhibited by vanadate in a dose-dependent manner as indicated by lack of epithelial alveoli compared to the contralateral nontreated gland controls. Mammary glands in the differentiation medium after four days in the presence of vanadate did not differentiate into alveoli. Instead, they exhibited prominent terminal end buds and lost the distinctive epithelial structures. The inhibitory effect of vanadate on mammary epithelial cell differentiation was irreversible after one day of treatment. Immunohistochemical staining for PCNA (Proliferating Cell Nuclear Antigen) showed that vanadate-treated glands exhibited elevated proliferation signals in the differentiation medium. Expression of beta -casein protein in the vanadate-treated glands decreased dramatically and progressively. Short-term exposure (up to 72 hours) of mammary glands to vanadate resulted in an increase in mammary epithelial cell density and loss of organization of the mammary structures. TUNEL assay of mammary glands with prolonged exposure to vanadate revealed widespread apoptosis. Furthermore, some cells were still proliferating or expressing beta -casein after prolonged exposure to vanadate. Taken together, these data indicate that vanadate treatment blocks mammary epithelial cell differentiation and promotes abnormal proliferation and apoptosis, likely through the inhibition of protein tyrosine phosphatase-mediated signaling. (C) 2001 Wiley-Liss, Inc. C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. NCI, Tumor Immunol & Biol Lab, Mol & Cellular Endocrinol Sect, Bethesda, MD 20892 USA. RP Xiao, ZXJ (reprint author), Boston Univ, Sch Med, Dept Med, 88 E Newton St,E605, Boston, MA 02118 USA. EM jxiao@bu.edu FU NHLBI NIH HHS [HL47049] NR 52 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2001 VL 222 IS 3 BP 354 EP 367 DI 10.1002/dvdy.1193 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 489XT UT WOS:000172018600004 PM 11747071 ER PT J AU Li, CL Guo, HM Xu, XL Weinberg, W Deng, CX AF Li, CL Guo, HM Xu, XL Weinberg, W Deng, CX TI Fibroblast growth factor receptor 2 (Fgfr2) plays an important role in eyelid and skin formation and patterning SO DEVELOPMENTAL DYNAMICS LA English DT Article DE mouse; Fgfr2; cell proliferation; morphogenetic transition; organogenesis ID TARGETED DISRUPTION; LIMB DEVELOPMENT; HAIR FOLLICLE; INNER-EAR; MICE; MOUSE; MORPHOGENESIS; PROLIFERATION; EXPRESSION; MUTATION AB Initiating as protruding ridges above and below the optic vesicle, the eyelids of mice grow across the eye and temporarily fuse in fetal life. Mutations of a number of genes disrupt this developmental process and result in a birth defect, "open-eyelids at birth." Here we show that a critical event for eyelid induction occurs at embryonic day 11.5 (E11.5) when the single cell-layered ectoderm in the presumptive eyelid territory increases proliferation and undergoes morphologic transition to form cube-shaped epithelial cells. Using embryos lacking the Fgfr2 Ig domain III (Fgfr2(Delta III/Delta III)) generated by tetraploid rescue and chimeric embryo formation approaches, we demonstrate that this event is controlled by Fgfr2 signals as the Fgfr2(Delta III/Delta III) mutation blocks these changes and results in embryos without eyelids. Fgfr2 and its ligands are differentially expressed in the ectoderm and underlying mesenchyme and function in a reciprocal interacting loop that specifies eyelid development. We also demonstrate that similar defects account for failure of skin formation at early stages. Interestingly, Fgfr2-independent skin formation occurs at E14.5 mutant embryos, resulting in much thinner, yet well-differentiated epidermis. Notably, mutant skin remains thin with decreased hair density after transplantation to wild-type recipients. These data demonstrate an essential role of Fgfr2 in eyelid and skin formation and patterning. Published 2001 Wiley-Liss, Inc. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, DMA, Bethesda, MD USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 56 TC 44 Z9 47 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2001 VL 222 IS 3 BP 471 EP 483 DI 10.1002/dvdy.1205 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 489XT UT WOS:000172018600014 PM 11747081 ER PT J AU Appelbaum, M Belsky, J Booth, C Bradley, R Brownell, C Burchinal, M Caldwell, B Campbell, S Clarke-Stewart, A Cox, M Friedman, S Hirsh-Pasek, K Huston, A Jaeger, E Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Spieker, S Vandell, DL Weinraub, M AF Appelbaum, M Belsky, J Booth, C Bradley, R Brownell, C Burchinal, M Caldwell, B Campbell, S Clarke-Stewart, A Cox, M Friedman, S Hirsh-Pasek, K Huston, A Jaeger, E Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Phillips, D Pianta, R Spieker, S Vandell, DL Weinraub, M CA NICHD Early Child Care Res Network TI Child-care and family predictors of preschool attachment and stability from infancy SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID BEHAVIOR; METAANALYSIS; CONSEQUENCES; SECURITY; QUALITY; PARENT; LIFE; AGE AB This study used multinomial logistic regression to examine relationships between child-care experience (in the context of overall family functioning) and preschool attachment. Attachment behavior was assessed at 36 months with the Strange Situation, and A, B, C, and D attachment classifications were assigned using the MacArthur coding system. Maternal sensitivity was the strongest predictor of preschool attachment classification. With respect to child-care effects, as at 15 months, no child-care factors (quantity, quality, or type) predicted, in and of themselves, attachment security at 36 months. However, I of 3 interactions involving child care that were detected at 15 months reemerged at 36 months: When maternal sensitivity was low, more hours per week in care somewhat increased the risk of the insecure-ambivalent (C) classification. There was significant but modest stability of attachment classifications from 15 to 36 months, especially for children with A and C classifications. C1 NICHHD, Publ Informat & Commun Branch, Bethesda, MD 20892 USA. Univ London Birkbeck Coll, London WC1E 7HX, England. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Washington, Seattle, WA 98195 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR USA. Univ Calif Irvine, Irvine, CA 92717 USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Texas, Austin, TX 78712 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Harvard Univ, Cambridge, MA 02138 USA. Univ N Carolina, Greensboro, NC 27412 USA. Univ Texas, Dallas, TX 75230 USA. Georgetown Univ, Washington, DC 20057 USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Washington, Seattle, WA 98195 USA. Univ Wisconsin, Madison, WI 53706 USA. RP Appelbaum, M (reprint author), NICHHD, Publ Informat & Commun Branch, Bldg 31,2A32,31 Ctr Dr, MSC 2425, Bethesda, MD 20892 USA. RI Marshall, Nancy/C-3428-2012 NR 61 TC 97 Z9 97 U1 5 U2 25 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD NOV PY 2001 VL 37 IS 6 BP 847 EP 862 DI 10.1037//0012-1649.37.6.847 PG 16 WC Psychology, Developmental SC Psychology GA 487EY UT WOS:000171861700010 ER PT J AU Looker, HC Knowler, WC Hanson, RL AF Looker, HC Knowler, WC Hanson, RL TI Changes in BMI and weight before and after the development of type 2 diabetes SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; PIMA-INDIANS; OBESITY; NIDDM; GAIN; COMPLICATIONS; RETINOPATHY; OVERWEIGHT; PREVALENCE; MORTALITY AB OBJECTIVE - To examine weight changes occurring before and after the diagnosis of diabetes and the association Of these changes with treatment and microvascular complications. RESEARCH DESIGN AND METHODS - We undertook an analysis of serial examinations conducted between 1965 and 2000 in residents of the Gila River Community in Central Arizona. Data were taken from 4,226 examinations of 816 individuals in whom diabetes developed over the course of a longitudinal study and who had undergone a nondiabetic examination within 4 years preceding diagnosis, We measured changes in BMI between examinations. RESULTS - Before diagnosis Of diabetes, there were steady gains in weight: mean BMI climbed between 0.43 and 0.71 kg/m(2) per year. After diagnosis, the weight gain declined, and weight loss was generally seen the mean rate of change of BMI ranged between -0.61 and +0.22 kg/m(2) per year. When current treatment was considered, there was greater weight stability in individuals taking insulin compared with those not taking hypoglycemic medication. Medication was a statistically significant factor for change in weight for Most of the time intervals analyzed. There was no statistically significant association with retinopathy or nephropathy. CONCLUSIONS - Before development of diabetes, there was a progressive rise in weight , and after diagnosis, there was a tendency toward weight loss, Weight-loss interventions in individuals with diabetes will need to account for this tendency if they are to successfully modify, the course of the disease. C1 NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix, AZ USA. RP Looker, HC (reprint author), NIDDK, Diabet & Arthrit Epidemiol Sect, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 28 TC 64 Z9 68 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2001 VL 24 IS 11 BP 1917 EP 1922 DI 10.2337/diacare.24.11.1917 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488LZ UT WOS:000171937800012 PM 11679457 ER PT J AU Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Gingerich, R Egan, JM Finegood, DT Elahi, D AF Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Gingerich, R Egan, JM Finegood, DT Elahi, D TI Effect of glucagon-like peptide 1 on non-insulin-mediated glucose uptake in the elderly patient with diabetes SO DIABETES CARE LA English DT Article ID IN-VITRO; IV; POLYPEPTIDE; DEGRADATION; DISPOSAL; HORMONE; DISPOSITION; TOLERANCE; RATES; NIDDM AB An important cause of elevated glucose levels in elderly patients with diabetes is an alteration in non-insulin-mediated glucose uptake (NIMGU). Glucagon-like peptide 1 (GLP-1) is an intestinal insulinotropic hormone. It has been proposed that this hormone also lowers glucose levels by enhancing NIMGU. This study was conducted to determine whether GLP-1 augments ;NIMGU in elderly patients with diabetes, a group in which NIMGU is known to be impaired. Studies were conducted on 10 elderly patients with type 2 diabetes (aged 75 +/- 2 years, BMI 27 +/- 1 kg/m(2)) who under-went paired 240-min glucose clamp studies. In each study, octreotide was infused to suppress endogenous insulin release, and tritiated glucose methodology was used to measure glucose production and disposal rates. For the first 180 min, no glucose was infused. From 180 to 240 min, glucose was increased to 11 mmol/l using the glucose clamp protocol. In the GLP-1 study, GLP-1 was infused from 30 to 240 min. In a subsequent control Study, insulin was infused using the glucose clamp protocol from 30 to 240 min to match the insulin levels that occurred during the GLP-1 infusion study, During hyperglycemia, GLP-1 enhanced glucose disposal (control study: 2.52 +/- 0.19 mg . kg(-1). min(-1) GLP-1 study: 2.90 +/- 0.17 mg . kg(-1). min(-1); P < 0.0001). Hepatic glucose output,vas not different between studies. We conclude that GLP-1 may partially reverse the defect in NIMGU that occurs in elderly patients with diabetes. C1 Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Physiol, Vancouver, BC V5Z 1M9, Canada. Simon Fraser Univ, Sch Kinesiol, Burnaby, BC V5A 1S6, Canada. NIA, Gerontol Res Ctr, Lab Clin Physiol, NIH, Baltimore, MD 21224 USA. Linco Res, St Charles, MO USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Lab Mol Endocrinol, Howard Hughes Med Inst, Boston, MA USA. RP Meneilly, GS (reprint author), Vancouver Hosp & Hlth Sci Ctr, UBC Site,2211 Wesbrook Mall,Rm S 169, Vancouver, BC V6T 2B5, Canada. NR 36 TC 45 Z9 46 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2001 VL 24 IS 11 BP 1951 EP 1956 DI 10.2337/diacare.24.11.1951 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488LZ UT WOS:000171937800018 PM 11679463 ER PT J AU Sumner, AE Farmer, NM Cochran, CS Sebring, NG Vanevski, K Reynolds, JC Premkumar, A Boston, RC AF Sumner, AE Farmer, NM Cochran, CS Sebring, NG Vanevski, K Reynolds, JC Premkumar, A Boston, RC TI Obese premenopausal African-American women with normal and impaired glucose tolerance have a similar degree of insulin resistance but differ in beta-cell function SO DIABETES CARE LA English DT Article ID VISCERAL ADIPOSE-TISSUE; FREE FATTY-ACID; ABDOMINAL FAT; SENSITIVITY; SECRETION; PREDICT; WHITE; RISK AB OBJECTIVE - To determine whether insulin resistance and secretion differ in obese premenopausal African-American women with and without glucose intolerance. RESEARCH DESIGN AND METHODS - A total of 63 women underwent oral glucose tolerance tests (OGTTs). A total of 48 women underwent frequently sampled intravenous glucose tolerance tests (FSIGTs). Insulin resistance was determined from the insulin sensitivity index (S-I) from the FSIGT. Insulin secretion during the OGTT was determined by (I-30 (min)-I-0 min)/(G(30 min) - - G(0 min)) and during the FSIGT by the acute insulin response to glucose (AIRg), The disposition index, the product of AIRg and S-I was used to determine whether AlRg was adequate to compensate for insulin resistance. Statistical analyses included one-way analysis of variance with Bonferroni corrections for multiple comparisons and regression analyses. RESULTS - The women were divided into three groups: nonobese glucose tolerant (n = 32), obese glucose tolerant (n = 17), and obese glucose intolerant (n = 14). The BMI of the three groups were 24.8 +/- 2.3, 37.8 +/- 5.5, and 42.0 +/- 7.6 kg/m(2) (mean +/- SD) respectively (P < 0.0001). The ages of the three groups were 34.9 +/- 8.4, 32.1 +/- 5.0, and 41.1 +/- 6.3 years (P = 0.011). S-I was higher in the nonobese women than in the obese glucose-tolerarnt women (3.99 +/- 1.44 vs. 2.66 +/- 2.14 l (.) mU(-1) (.) min(-1), P = 0.03). S-I was similar in the obese glucose-intolerant, and obese glucose-tolerant women (2.12 +/- 1.27 vs 2.66 +/- 2.14 l(.)mU(-1.)min(-1), P = 0.9). OGTT showed that insulin secretion was lower in the glucose-intolerant than the obese glucose-tolerant women (1.73 +/- 1.38 vs. 3.62 +/- 2.11, P = 0.005). FSIGT showed that AIRg was not significantly lower in glucose-intolerant than in obese glucose-tolerant women (807 +/- 665 vs.. 1,253 +/- 655 mU(-1.)l(-1.)min, P = 0.078). The disposition index was lower in glucose-in tolerant than in obese glucose-tolerant women (1,324 +/- 1,061 vs. 2,656 +/- 1,415, P = 0.014). CONCLUSIONS - Obese premenopausal African-American women with and without glucose intolerance have a similar degree of insulin resistance but differ in insulin secretion. C1 NIDDK, NIH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Sumner, AE (reprint author), NIDDK, NIH, Bldg 10,Rm 8S235D, Bethesda, MD 20892 USA. NR 26 TC 5 Z9 7 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2001 VL 24 IS 11 BP 1978 EP 1983 DI 10.2337/diacare.24.11.1978 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488LZ UT WOS:000171937800023 PM 11679468 ER PT J AU Bennett, PH Knowler, WC Krakoff, J AF Bennett, PH Knowler, WC Krakoff, J TI Idiopathic Type 1 Diabetes? SO DIABETES CARE LA English DT Letter ID KETOACIDOSIS C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. RP Bennett, PH (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. NR 4 TC 1 Z9 2 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2001 VL 24 IS 11 BP 2012 EP 2012 DI 10.2337/diacare.24.11.2012 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488LZ UT WOS:000171937800041 PM 11679486 ER PT J AU Neamat-Allah, M Feeney, SA Savage, DA Maxwell, AP Hanson, RL Knowler, WC El Nahas, AM Plater, ME Shaw, J Boulton, AJM Duff, GW Cox, A AF Neamat-Allah, M Feeney, SA Savage, DA Maxwell, AP Hanson, RL Knowler, WC El Nahas, AM Plater, ME Shaw, J Boulton, AJM Duff, GW Cox, A TI Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus SO DIABETIC MEDICINE LA English DT Article DE aldose reductase; polymorphism; Type 1 diabetes; Type 2 diabetes; diabetic nephropathy ID FAMILIAL PREDISPOSITION; PIMA-INDIANS; SUSCEPTIBILITY; RETINOPATHY; 5'-END; COMPLICATIONS; EXPRESSION; DISEASE; RATS; NEUROPATHY AB Aims To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta-analysis of published results. Methods We have investigated the role of two aldose reductase polymorphisms in four independent cohorts of cases and controls (two each with Type 1 and Type 2 diabetes) drawn from two ethnic populations, including 471 patients with nephropathy and 494 control diabetic patients without nephropathy. A C/T transition at position -106, and a (CA)(n) microsatellite marker 2.1 kb from the start site of the aldose reductase gene were genotyped in nephropathic patients and non-nephropathic controls from each cohort. Results Carriage of the -106 T allele was significantly associated with diabetic nephropathy in three of the four study groups. The Mantel-Haenszel combined odds ratio was 2.22 (95% Cl 1.69, 2.94), P = 1.05 x 10(-8). We found no evidence for association of the microsatellite marker with nephropathy, despite moderate levels of disequilibrium between the two markers. Meta-analysis of published data yielded no evidence for association of the microsatellite marker with diabetic nephropathy in Type 2 diabetes, but varying degrees of association with diabetic nephropathy in Type 1 diabetes. Conclusions Meta-analyses provide more convincing evidence of a role for the ALR2-106 marker than for the microsatellite marker in diabetic nephropathy (DN). More studies are now required to confirm these results and to establish whether the ALR2-106 polymorphism has a functional role in DN. C1 Univ Sheffield, Sch Med, Inst Canc Studies, Div Med & Mol Genet, Sheffield S10 2RX, S Yorkshire, England. Queens Univ Belfast, Dept Med Genet, Belfast, Antrim, North Ireland. Belfast City Hosp, Reg Nephrol Unit, Belfast BT9 7AD, Antrim, North Ireland. NIDDK, NIH, Phoenix, AZ USA. No Gen Hosp, Sheffield Kidney Inst, Sheffield S5 7AU, S Yorkshire, England. Royal Hallamshire Hosp, Diabet Unit, Sheffield S10 2JF, S Yorkshire, England. Manchester Royal Infirm, Manchester M13 9WL, Lancs, England. RP Cox, A (reprint author), Univ Sheffield, Sch Med, Inst Canc Studies, Div Med & Mol Genet, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. RI Shaw, Jonathan/E-7388-2010; Hanson, Robert/O-3238-2015; OI Shaw, Jonathan/0000-0002-6187-2203; Hanson, Robert/0000-0002-4252-7068; Cox, Angela/0000-0002-5138-1099; Maxwell, Alexander P./0000-0002-6110-7253 NR 36 TC 31 Z9 36 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD NOV PY 2001 VL 18 IS 11 BP 906 EP 914 DI 10.1046/j.0742-3071.2001.00598.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 496NK UT WOS:000172401500009 PM 11703436 ER PT J AU Krausz, KW Goldfarb, I Buters, JTM Yang, TJ Gonzalez, FJ Gelboin, HV AF Krausz, KW Goldfarb, I Buters, JTM Yang, TJ Gonzalez, FJ Gelboin, HV TI Monoclonal antibodies specific and inhibitory to human cytochromes P4502C8, 2C9, and 2C19 SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN LIVER-MICROSOMES; ANTIPEPTIDE ANTIBODY; METABOLISM; CDNA; ENZYMES; HYDROXYLATION; 7-ETHOXYCOUMARIN; MEPHENYTOIN; TOLBUTAMIDE; EXPRESSION AB Hybridomas were isolated that produce 13 monoclonal antibodies (mAbs) that are specific and highly inhibitory to members of the human P450 2C subfamily, 2C8, 2C9,2C9*2, and 2C19. Many of the mAbs to P450 2C8, 2C9, and 2C19 are specific and exhibit potent inhibitory activity (85-95%). mAb 281-1-1 specifically binds, immunoblots, and strongly inhibits the activity of P450 2C8. mAb 763-15-5 specifically binds and strongly inhibits the activity of P450 2C9. mAb 1-7-4-8 specifically binds and strongly inhibits the activity of P450 2C19. The other mAbs bind and inhibit sets and subsets of the P450 2C family. The single and the combinatorial use of the mAbs can "reaction phenotype", i.e., determine the metabolic contribution and interindividual variation of a P450 isoform for the metabolism of a drug or nondrug xenobiotic in human liver microsomes. The utility of the mAb-based analytic system was examined with the model substrates Taxol (paclitaxel), diazepam, tolbutamide, diclofenac, mephenytoin, and imipramine. The mAb system can identify drugs metabolized by a common P450 or several P450s and polymorphic P450s. The mAb system identifies drugs or drug metabolic pathways that are catalyzed by a single P450 and thus may be used for in vivo phenotyping. The mAb system can identify whether a particular drug is metabolized by a single P450 that may exhibit polymorphic expression in humans. The mAb system offers large potential for studies of cytochrome P450 function useful in drug discovery and reduces the possibility of adverse drug reactions due to polymorphisms and drug interactions. C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gelboin, HV (reprint author), NCI, Mol Carcinogenesis Lab, NIH, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. RI Buters, Jeroen/G-5070-2011 NR 39 TC 27 Z9 28 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV PY 2001 VL 29 IS 11 BP 1410 EP 1423 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 485QG UT WOS:000171765600008 PM 11602516 ER PT J AU Sciortino, S Gurtner, A Manni, I Fontemaggi, G Dey, A Sacchi, A Ozato, K Piaggio, G AF Sciortino, S Gurtner, A Manni, I Fontemaggi, G Dey, A Sacchi, A Ozato, K Piaggio, G TI The cyclin B1 gene is actively transcribed during mitosis in HeLa cells SO EMBO REPORTS LA English DT Article ID DEPENDENT REGULATION; MITOTIC REPRESSION; S-PHASE; PROMOTER; EXPRESSION; INHIBITION; CHROMATIN; COMPLEX AB In mammalian cells, the expression level of the cyclin B1 gene plays a critical role in the progression through mitosis. Here we demonstrate that the transcriptional activity of the human cyclin B1 promoter, as well as the rate of gene transcription, is high during mitosis. Indeed, the cyclin B1 promoter maintains an open chromatin configuration at the mitotic stage. Consistent with this, we show that the cyclin B1 promoter is occupied and bound to NF-Y during mitosis in vivo. Our results provide the first example of RNA polymerase II-dependent transcription during mitosis in mammalian cells. C1 Ist Regina Elena, Dipartimento Oncol Sperimentale, I-00158 Rome, Italy. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Piaggio, G (reprint author), Ist Regina Elena, Dipartimento Oncol Sperimentale, Via Messi DOro 156, I-00158 Rome, Italy. OI gurtner, aymone/0000-0002-7661-9059; piaggio, giulia/0000-0003-2114-1892; Fontemaggi, Giulia/0000-0001-8332-8842 NR 21 TC 38 Z9 38 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD NOV PY 2001 VL 2 IS 11 BP 1018 EP 1023 DI 10.1093/embo-reports/kve223 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 496CX UT WOS:000172379200013 PM 11606417 ER PT J AU Geary, N Asarian, L Korach, KS Pfaff, DW Ogawa, S AF Geary, N Asarian, L Korach, KS Pfaff, DW Ogawa, S TI Deficits in E2-dependent control of feeding, weight gain, and cholecystokinin satiation in ER-alpha null mice SO ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; CENTRAL-NERVOUS-SYSTEM; FEMALE RATS; FOOD-INTAKE; GENE DISRUPTION; BODY-WEIGHT; OVARIECTOMIZED RATS; MEAL PATTERNS; EXPRESSION; ESTRADIOL AB To test the role of gene expression of the classical ER (ER alpha) in the inhibitory effects of E on food intake and body weight, we ovariectomized and administered E2 benzoate (75 pg/d) or vehicle to wild-ty pe (WT) mice and mice with a null mutation of ER alpha (alpha ERKO). Mice were ovariectomized at age 9 wk, at which time there was no significant effect of genotype on food intake or body weight. During an 18-d test after recovery from ovariectomy, vehicle-treated WT mice increased daily food intake and gained more body weight than E2-treated WT mice, whereas food intake and body weight gain were not different in E2- and vehicle-treated aERKO mice. Carcass analysis revealed parallel changes in body lipid content, but not water or protein content. Because an increase in the potency of the peripheral cholecystokinin (CCK) satiation-signaling system mediates part of E2's influence on feeding in rats, the influence of ip injections of 250 mug of the selective CCKA receptor antagonist devazepide was then tested. Devazepide increased 3-h food intake in E2-treated WT mice, but was ineffective in both groups of alpha ERKO mice. Furthermore, ip injections of 4 mug/kg CCK-8 increased the number of cells expressing c-Fos immunoreactivity in the nuclei of the solitary tract of E2-treated WT mice more than it did in vehicle-treated WT mice, whereas E2 had no such effect in alpha ERRO mice. Thus, ER alpha is necessary for normal responsivity of food intake, body weight, adiposity, and the peripheral CCK satiation-signaling system to E2 in mice, and ER beta is not sufficient for any of these effects. This is the first demonstration that ER alpha gene expression is involved in the estrogenic control of feeding behavior and weight regulation of female mice. C1 Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Psychiat,Bourne Behav Res Lab, White Plains, NY 10605 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Rockefeller Univ, Neurobiol & Behav Lab, New York, NY 10021 USA. RP Geary, N (reprint author), Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, Dept Psychiat,Bourne Behav Res Lab, 21 Bloomingdale Rd, White Plains, NY 10605 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 46 TC 158 Z9 164 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2001 VL 142 IS 11 BP 4751 EP 4757 DI 10.1210/en.142.11.4751 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488BT UT WOS:000171915300019 PM 11606440 ER PT J AU Kreda, SM Sumner, M Fillo, S Ribeiro, CM Luo, GX Xie, WH Daniel, KW Shears, S Collins, S Wetsel, WC AF Kreda, SM Sumner, M Fillo, S Ribeiro, CM Luo, GX Xie, WH Daniel, KW Shears, S Collins, S Wetsel, WC TI alpha(1)-adrenergic receptors mediate LH-releasing hormone secretion through phospholipases C and A(2) in immortalized hypothalamic neurons SO ENDOCRINOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; ARACHIDONIC-ACID RELEASE; LUTEINIZING-HORMONE; RAT-BRAIN; MOLECULAR-CLONING; CELL-LINE; ALPHA(1D)-ADRENERGIC RECEPTOR; ALPHA-1-ADRENERGIC RECEPTOR; PULSATILE RELEASE; MESSENGER-RNA AB Norepinephrine has long been known to stimulate the pulsatile and preovulatory release of LH-releasing hormone (LHRH). In vivo and in vitro studies indicate that these effects are mediated primarily through alpha (1)-adrenergic receptors (alpha (1)-ARs). With the immortalized hypothalamic LHRH neurons, we have found that alpha (1)-adrenergic agents directly stimulate the secretion of LHRH in a dose-dependent manner. Ligand binding and RNA studies demonstrate that the GT1 cells contain both alpha (1A)- and alpha (1B)-ARs. Competition binding experiments show that approximately 75% of the binding is due to alpha (1B)-ARs; the remainder is made up of alpha (1A)-ARs. Receptor activation leads to stimulation of PLC.PLC beta1 and PLC beta3 are expressed in GT1 neurons, and these PLCs are probably responsible for the release of diacylglycerol and IP as well as the increase in intracellular calcium. The mobilization of cytoplasmic calcium is sufficient to stimulate cytosolic PLA(2) (cPLA(2)) and release arachidonic acid. A dissection of the contributions of the phospholipases to LHRH secretion suggests that cPLA(2) acts downstream of PLC and that it significantly augments the PLC-stimulated LHRH secretory response. Inasmuch as the alpha (1)-ARs are known to play a critical role in LHRH physiology, we propose that both PLC and cPLA(2) are critical in regulating and amplifying LHRH release. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. NIEHS, Lab Signal transduct, Res Triangle Pk, NC 27709 USA. RP Wetsel, WC (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3497,028 CARL Bldg, Durham, NC 27710 USA. RI Ribeiro, Carla Maria/A-6955-2009 NR 61 TC 12 Z9 13 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2001 VL 142 IS 11 BP 4839 EP 4851 DI 10.1210/en.142.11.4839 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488BT UT WOS:000171915300031 PM 11606452 ER PT J AU Dupont, J Khan, J Qu, BH Metzler, P Helman, L LeRoith, D AF Dupont, J Khan, J Qu, BH Metzler, P Helman, L LeRoith, D TI Insulin and IGF-1 induce different patterns of gene expression in mouse fibroblast NIH-3T3 cells: Identification by cDNA microarray analysis SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3'-KINASE; TYROSINE KINASE; BINDING-PROTEINS; RECEPTOR KINASE; SHC PROTEINS; PHOSPHORYLATION; SUBSTRATE; DOMAIN AB The IGF-1 receptor and the related insulin receptor are similar in structure and activate many of the same postreceptor signaling pathways, yet they mediate distinct biological functions. It is still not understood how the specificity of insulin vs. IGF-1 signaling is controlled. In this study, we have used cDNA microarrays to monitor the gene expression patterns that are regulated by insulin and IGF-1. Mouse fibroblast NIH-3T3 cells expressing either the wild-type human IGF receptor or the insulin receptor were stimulated with either IGF-1 or insulin, respectively. Thirty genes, 27 of which were not previously known to be IGF-1 responsive, were up-regulated by IGF-1 but not by insulin. Nine genes, none of which was previously known to be insulin responsive, were up-regulated by insulin but not by IGF-1. The IGF- and insulin-induced regulation of 10 of these genes was confirmed by Northern blot analysis. Interestingly, more than half of the genes up-regulated by IGF-1 are associated with mitogenesis and differentiation, whereas none of the genes specifically up-regulated by insulin are associated with these processes. Our results indicate that under the conditions used in this study, IGF-1 is a more potent activator of the mitogenic pathway than insulin in mouse fibroblast NIH-3T3 cells. C1 NIDDKD, Sect Cellular & Mol Physiol, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Genet Branch, NHGRI, Bethesda, MD 20892 USA. NIH, Mol Oncol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDKD, Sect Cellular & Mol Physiol, Clin Endocrinol Branch, NIH, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 60 TC 70 Z9 72 U1 1 U2 6 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2001 VL 142 IS 11 BP 4969 EP 4975 DI 10.1210/en.142.11.4969 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488BT UT WOS:000171915300044 PM 11606465 ER PT J AU Arima, H House, SB Gainer, H Agiulera, G AF Arima, H House, SB Gainer, H Agiulera, G TI Direct stimulation of arginine vasopressin gene transcription by cAMP in parvocellular neurons of the paraventricular nucleus in organotypic cultures SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA; SUPRAOPTIC NUCLEI; OXYTOCIN NEURONS; RAT HYPOTHALAMUS; CYCLIC-AMP; EXPRESSION; RESPONSES; PROTEIN; HYPEROSMOLALITY; SECRETION AB The regulation of arginine vasopressin (AVP) gene transcription in the paraventricular nucleus (PVN) was studied in rat hypothalamic organotypic cultures using intronic in situ hybridization. While AVP heteronuclear (hn) RNA was not detected in the PVN under basal conditions, a marked induction of AVP hnRNA was observed after 2 and 3 h incubation of slices with forskolin. In contrast to the stimulatory effects of forskolin, phorbol 12-myristate 13-acetate (PMA) was completely ineffective in inducing AVP ImRNA in the PVN at any time examined (1-3 h), Forskolin-induced AVP ImRNA expression was unaffected by blockade of neurotransmission by the sodium channel inhibitor, tetrodotoxin, indicating that forskolin acts directly on AVP cells in the PVN. Dual staining in situ hybridization of forskolin-stimulated hypothalamic sections using both radiolabeled AVP hnRNA and digoxigenin-labeled CRH mRNA probes revealed colocalization of both transcripts, indicating AVP hnRNA is expressed in the parvocellular neurons. The data demonstrate that cAMP directly activates AVP gene transcription in parvocellular neurons of the PVN. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINCDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Arima, H (reprint author), Nagoya Univ, Sch Med, Dept Internal Med 1, Syowa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan. RI Arima, Hiroshi/I-7383-2014 OI Arima, Hiroshi/0000-0003-3746-1997 NR 30 TC 21 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2001 VL 142 IS 11 BP 5027 EP 5030 DI 10.1210/en.142.11.5027 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488BT UT WOS:000171915300050 PM 11606471 ER PT J AU Schroeder, JC Olshan, AF Baric, R Dent, GA Weinberg, CR Yount, B Cerhan, JR Lynch, CF Schuman, LM Tolbert, PE Rothman, N Cantor, KP Blair, A AF Schroeder, JC Olshan, AF Baric, R Dent, GA Weinberg, CR Yount, B Cerhan, JR Lynch, CF Schuman, LM Tolbert, PE Rothman, N Cantor, KP Blair, A TI Agricultural risk factors for t(14;18) subtypes of non-Hodgkiin's lymphoma SO EPIDEMIOLOGY LA English DT Article DE lymphoma; non-Hodgkin; case-control studies; EM algorithm; translocation (genetics); genes; bcl-21; agriculture; pesticides; molecular ID CANCER MORTALITY; MALIGNANT-LYMPHOMAS; STRUCTURAL-ANALYSIS; CELL SURVIVAL; BCL-2 GENE; EXPOSURE; WORKERS; TRANSLOCATION; EPIDEMIOLOGY; INDUSTRY AB The t(14;18) translocation is a common somatic mutation in non-Hodgkin's lymphoma (NHL) that is associated with bcl-2 activation and inhibition of apoptosis. We hypothesized that some risk factors might act specifically along t(14;18)-dependent pathways, leading to stronger associations with t(14;18)-positive than t(14;18)-negative non-Hodgkin's lymphoma. Archival biopsies from 182 non-Hodgkin's lymphoma cases included in a case-control study of men in Iowa and Minnesota (the Factors Affecting Rural Men, or FARM study) were assayed for t(14;18) using polymerase chain reaction amplification; 68 (37%) were t(14; 18)-positive. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for various agricultural risk factors and t(14;18)-positive and -negative cases of non-Hodgkin's lymphoma, based on polytomous logistic regression models fit using the expectation-maximization (EM) algorithm. T(14; 18)-positive non-Hodgkin's lymphoma was associated with farming (OR 1.4, 95% CI = 0.9-2.3), dieldrin (OR 3.7, 95% Cl = 1.9-7.0), toxaphene (OR 3.0, 95% CI = 1.5-6.1), lindane (OR 2.3, 95% CI = 1.3-3.9), atrazine (OR 1.7, 95% Cl = 1.0-2.8), and fungicides (OR 1.8, 95% Cl = 0.9-3.6), in marked contrast to null or negative associations for the same self-reported exposures and t(14;18)-negative non-Hodgkin's lymphoma. Causal relations between agricultural exposures and t(14;18)-positive non-Hodgkin's lymphoma are plausible, but associations should be confirmed in a larger study. Results suggest that non-Hodgkin's lymphoma classification based on the t(14;18) translocation is of value in etiologic research. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NCI, Occupat & Epidemiol Branch, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Pub Hlth, Atlanta, GA 30322 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Mayo Clin, Rochester, MN USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. RP Schroeder, JC (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Tolbert, Paige/A-5676-2015 FU NCI NIH HHS [N01-CP-11020, R03CA71617, K07 CA64220] NR 63 TC 79 Z9 82 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2001 VL 12 IS 6 BP 701 EP 709 DI 10.1097/00001648-200111000-00020 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 485CT UT WOS:000171736500019 PM 11679800 ER PT J AU Woolhiser, MR Okayama, Y Gilfillan, AM Metcalfe, DD AF Woolhiser, MR Okayama, Y Gilfillan, AM Metcalfe, DD TI IgG-dependent activation of human mast cells following up-regulation of Fc gamma RI by IFN-gamma SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE mast cell; Fc receptor; degranulation; cytokine; IgG ID NECROSIS-FACTOR-ALPHA; COLONY-STIMULATING FACTOR; HIGH-AFFINITY; RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; RECEPTOR; NEUTROPHILS; VASCULITIS; EXPRESSION AB It has been reported that Fc gamma RI is up-regulated on human mast cells (huMC) by IFN-gamma and aggregation of this receptor using mouse F(ab')(2) specific for receptor-bound, mouse anti-CD64 F(ab')2 results in activation. To determine whether huMC can similarly be stimulated by aggregation of Fc gamma RI-bound human IgG, IFN-gamma -treated, CD34(+)-derived, cultured huMC were sensitized with human immunoglobulins and activation was evaluated following addition of antibodies specific for each IgG isotype. Degranulation was also examined following simultaneous IgG- and IgE-dependent aggregation of Fc gamma RI and Fc epsilon RI. Activation of IFN-gamma -treated huMC sensitized with 100 ng/ml IgG(1) resulted in 40% beta -hexosaminidase (beta -hex) release; minimal degranulation was observed using IgG(2), IgG(3) or IgG(4). IgG(1)-dependent activation led to PGD(2) and LTC4 generation as well as elevated cytokine production, most notably TNF-alpha. Preincubation of cells with F(ab')(2) from CD64-specific clones 10.1 and 32.2 reduced IgG(1)-medlated beta -hex release by 46% and 74%, respectively. While IgG-dependent cell stimulation induced half-maximal degranulation by 11 min, IgE-dependent activation resulted in half maximal responses within 1 min. Simultaneous activation of huMC via Fc gamma RI and Fc epsilon RI led to additive degranulation using suboptimal concentrations of IgG(1) and IgE. Activation of huMC thus may occur via monomeric IgG and Fc gamma RI thereby providing a novel paradigm for huMC recruitment into inflammation. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. NR 31 TC 58 Z9 61 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2001 VL 31 IS 11 BP 3298 EP 3307 DI 10.1002/1521-4141(200111)31:11<3298::AID-IMMU3298>3.0.CO;2-U PG 10 WC Immunology SC Immunology GA 494JD UT WOS:000172278000019 PM 11745347 ER PT J AU Mazzei, M Miele, M Nieddu, E Barbieri, F Bruzzo, C Alama, A AF Mazzei, M Miele, M Nieddu, E Barbieri, F Bruzzo, C Alama, A TI Unsymmetrical methylene derivatives of indoles as antiproliferative agents SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE unsymmetrical methylene derivatives; indoles; coumarins; antiproliferative agents; indole-3-carbinol ID BREAST-CANCER CELLS; INDOLE-3-CARBINOL; CHEMOPREVENTION; MIGRATION; INVASION; ARREST; CYCLE AB Indole-3-carbinol is a natural product which has been shown to reduce the incidence of spontaneous and carcinogen-induced mammary tumours in animals, Eighteen unsymmetrical methylene derivatives of indoles were prepared by reaction of Mannich bases of 7-hydroxycoumarins with substituted indoles in acetic or propionic anhydride. The synthesised molecules were tested in vitro against the MCF7 and MDA-MB-231 breast cancer cell lines by MTT and cell count assays. Results from 16 tested compounds showed that 60% of them exerted some effects against the MDA-MB-231 compared to about 30% towards the MCF7. Among all, the 3-(7'-acetoxy-4-methylcoumarin-8'-yl)methyl-2-methylindole resulted the most effective in both cell lines, compared to indole-3-carbinol, In conclusion, these preliminary results report that some of these compounds might be promising potential antiproliferative agents. (C) 2001 Editions scientifiques et medicales Elsevier SAS. C1 Dept Pharmaceut Sci, I-16132 Genoa, Italy. Natl Canc Inst, Lab Pharmacol & Neurosci, I-16132 Genoa, Italy. RP Mazzei, M (reprint author), Dept Pharmaceut Sci, Viale Benedetto XV 3, I-16132 Genoa, Italy. RI Barbieri, Federica/L-8753-2015 OI Barbieri, Federica/0000-0001-8988-6896 NR 13 TC 7 Z9 7 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD NOV-DEC PY 2001 VL 36 IS 11-12 BP 915 EP 923 DI 10.1016/S0223-5234(01)01286-7 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 515ZX UT WOS:000173527600007 PM 11755234 ER PT J AU Green, PG Dahlqvist, SRA Isenberg, WM Miao, FJP Levine, JD AF Green, PG Dahlqvist, SRA Isenberg, WM Miao, FJP Levine, JD TI Role of adrenal medulla in development of sexual dimorphism in inflammation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE 17 beta-oestradiol; gonadectomy; oestrogen receptor; plasma extravasation; puberty; sympathoadrenal axis ID INDUCED PLASMA EXTRAVASATION; WALL INDUCED POLYARTHRITIS; MALE-RATS; MATERNAL-BEHAVIOR; INDUCED ARTHRITIS; JOINT INJURY; FEMALE RATS; KNEE-JOINT; TESTOSTERONE; BRADYKININ AB Many inflammatory diseases show a female predilection in adults, but not prepubertally. Because sex differences in the inflammatory response in the adult rat are mediated, in part, by sexual dimorphism in adrenal medullary function, we investigated the contribution of the adrenal medulla to the ontogeny of sexual dimorphism in inflammation. Whilst there was no sex difference in the magnitude of the plasma extravasation (PE) induced by the potent inflammatory mediator bradykinin (BK) in prepubertal rats, in adult rats BK-induced PE was markedly greater in males. Also, adult male rats, gonadectomized prior to puberty, had a lower magnitude of BK-induced PE than did adult male controls, whilst adult females gonadectomized prepubertally had higher BK-induced PE than did controls. In rats gonadectomized after puberty, the magnitude of BK-induced PE in adult males was not affected, whilst in females it resulted in significantly higher BK-induced PE, similar to the effect of prepubertal gonadectomy. When tested prepubertally, adrenal denervation increased the magnitude of BK-induced PE in females, but not in males. In contrast, in both males and females tested as adults, but castrated prepubertally, and in gonad-intact adult females, adrenal denervation significantly increased the magnitude of BK-induced PE. Adrenal denervation in prepubertal females given adult levels of 17 beta -oestradiol produced a marked enhancement in the denervation-induced increase in magnitude of BK-induced PE compared to females not exposed prematurely to sex hormones. These studies suggest that an adrenal medulla-dependent inhibition of BK-induced PE is present in female but not male rats, and is enhanced by oestrogen but suppressed by testosterone. C1 Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Hosp, Dept Rheumatol, SE-90185 Umea, Sweden. RP Green, PG (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, C-522,Box 0440, San Francisco, CA 94143 USA. RI Green, Paul/C-5943-2011 FU NINR NIH HHS [NR04880] NR 50 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2001 VL 14 IS 9 BP 1436 EP 1444 DI 10.1046/j.0953-816x.2001.01768.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 496XJ UT WOS:000172423400003 PM 11722605 ER PT J AU Kook, H Zeng, WH Chen, GB Kirby, M Young, NS Maciejewski, JP AF Kook, H Zeng, WH Chen, GB Kirby, M Young, NS Maciejewski, JP TI Increased cytotoxic T cells with effector phenotype in aplastic anemia and myelodysplasia SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MULTIPLE-SCLEROSIS PATIENTS; BONE-MARROW TRANSPLANTATION; PERFORIN MESSENGER-RNA; MEDIATED CYTOTOXICITY; PERIPHERAL-BLOOD; ANTITHYMOCYTE GLOBULIN; RHEUMATOID-ARTHRITIS; CLONAL EXPANSIONS; CD28 EXPRESSION; GRANZYME-A AB Objective. We hypothesized that an active autoimmune process in aplastic anemia (AA) corresponds to the expansion of cytotoxic lymphocytes (CTLs) displaying mature effector phenotype. We determined whether the numbers of effector CTLs in blood of patients with bone marrow failure syndromes are elevated and correlate with the disease activity and responsiveness to immunosuppression. Patients and Methods. We analyzed samples from patients with AA, myelodysplastic syndrome (MDS), polytransfused patients with nonimmune-mediated hematologic disease, and normal controls for the presence of effector T lymphocytes using four-color How cytometry. Expression of CD57 and loss of CD28 on CD8(+)CD3(+) CTL were used as markers for the terminal effector phenotype. In addition, intracellular staining for perforin and granzyme B was preformed. The numbers of effector CTL did not differ between healthy individuals and hematologic controls and the two groups were pooled. Results. The percentages of CD8(+)CD28(-) and CD8(+)CD28(-)CD57(+) cells were significantly higher in AA and MDS patients than in controls. There was a trend toward a gradual decrease in the effector CTLs from the high values observed in untreated new patients and patients who did not respond to immunosuppression, intermediate levels for partial responders and complete responders, to the lowest levels seen in controls. However, severity of pancytopenia did not correlate with the size of the effector cell population. In contrast to CD57(+) CTLs, expression of perforin or granzyme B in the cytotoxic effector cells did not differ in AA patients from those of controls. Conclusions. Our results indicate that phenotypically defined effector CTLs are increased in AA and MDS and the effector phenotype may be useful to isolate and characterize antigen-specific T cells in AA in order to delineate the possible inciting or driving agents in AA. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Maciejewski, JP (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 53 TC 68 Z9 75 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD NOV PY 2001 VL 29 IS 11 BP 1270 EP 1277 DI 10.1016/S0301-472X(01)00736-6 PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 490QA UT WOS:000172061500004 PM 11698122 ER PT J AU Vawter, MP Usen, N Thatcher, L Ladenheim, B Zhang, PS VanderPutten, DM Conant, K Herman, MM van Kammen, DP Sedvall, G Garver, DL Freed, WJ AF Vawter, MP Usen, N Thatcher, L Ladenheim, B Zhang, PS VanderPutten, DM Conant, K Herman, MM van Kammen, DP Sedvall, G Garver, DL Freed, WJ TI Characterization of human cleaved N-CAM and association with schizophrenia SO EXPERIMENTAL NEUROLOGY LA English DT Article DE synaptosome; MALDI-TOF; protein sequence; ventricular enlargement; protease; N-CAM; cell adhesion molecule; cell recognition molecule; schizophrenia; proteolysis ID CELL-ADHESION MOLECULE; TISSUE-PLASMINOGEN ACTIVATOR; SERINE-PROTEASE INHIBITOR; RECOGNITION MOLECULES; SYNAPTIC PLASTICITY; BIPOLAR DISORDER; NERVOUS-SYSTEM; EXPRESSION; NCAM; HIPPOCAMPUS AB The neural cell adhesion molecule (N-CAM) is a cell recognition molecule involved in cellular migration, synaptic plasticity, and CNS development. A 105- to 115-kDa isoform. of N-CAM (cleaved N-CAM or cN-CAM) is increased in schizophrenia in hippocampus, prefrontal cortex, and CSF. We purified and partially characterized cN-CAM, a putative novel isoform, and confirmed that the first 9 amino acids were identical to exon 1 of N-CAM, without the signal sequence. Analysis of trypsin-digested cN-CAM fragments by matrix-assisted laser desorption ionization on a time-of-flight mass spectrometer (MALDI-TOF) yielded peptides that could be identified as being derived from the first 548 amino acid residues of the expected N-CAM amino acid sequence. Immunological identification with four specific N-CAM antisera directed toward cytoplasmic, secreted, variable alternative spliced exon, or GPI epitopes failed to indicate other known splice variants. Neuraminidase treatment of cN-CAM produced a minor alteration resulting in a faster migrating immunoreactive band, indicating partial glycosylation of cN-CAM. Membranous particles from cytosolic brain extract containing cN-CAM were obtained by ultracentrifugation; however, CSF contained few such particles. cN-CAM and synaptophysin were colocalized on these particles. Both cN-CAM and N-CAM 180 were present in synaptosomal preparations of human brain. Following incubation of synaptosomes or brain tissue without protease inhibitors, N-CAM 180 was degraded and cN-CAM was increased. A cN-CAM-like band was present in human fetal neuronal cultures, but not in fetal astrocyte cultures. Thus, cN-CAM represents a protease- and neuraminidase-susceptible fragment possibly derived by proteolytic cleavage of N-CAM 180. An enlargement in ventricular volume in a group of adult patients with schizophrenia over a 2-year interval was found to be correlated with CSF cN-CAM levels as measured at the time of the initial MRI scan (r=0.53, P=0.01). cN-CAM is associated with ventricular enlargement; thus, the release of N-CAM fragments may be part of the pathogenic mechanism of schizophrenia in vulnerable brain regions such as the hippocampus and prefrontal cortex. Alternatively, the increases in cN-CAM in schizophrenia may be a reflection of a more general abnormality in the regulation of proteolysis or of extracellular matrix stability. (C) 2001 Academic Press. C1 NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch, Baltimore, MD 21224 USA. DirectGene, Annapolis, MD 21401 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. NIMH, Clin Brain Disorders Branch, IRP, Bethesda, MD 20892 USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA. Karolinska Hosp & Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Louisville, KY 40222 USA. Univ Calif Irvine, Irvine, CA 92697 USA. RP Freed, WJ (reprint author), NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch, 550 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 49 TC 52 Z9 55 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2001 VL 172 IS 1 BP 29 EP 46 DI 10.1006/exnr.2001.7790 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 491BH UT WOS:000172087800003 PM 11681838 ER PT J AU Newton, DL Rybak, SM AF Newton, DL Rybak, SM TI Antibody targeted therapeutics for lymphoma: new focus on the CD22 antigen and RNA SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE antibody; CD22; immunotoxin; lymphoma; ribonuclease ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; 16S RIBOSOMAL-RNA; ANTI-CD22 MONOCLONAL-ANTIBODY; HUMAN IMMUNOTOXIN ANALOG; PHASE-I; CYTOTOXIC RIBONUCLEASE; GROWTH-FACTOR; P-30 PROTEIN; RICIN-A AB The approval of antibodies for cancer treatment has provoked increased interest in the development of new and improved antibody-mediated therapies. This emerging approach centres on targeting CD22 on human B-cells with a monoclonal antibody (mAb). Anti-CD22 antibodies conjugated to a cytotoxic RNAse elicits potent and specific killing of the lymphoma cells in vitro and in human lymphoma models in severe combined immune deficiency (SCID) mice. RNA damage caused by RNAses could be an important alternative to standard DNA damaging chemotherapeutics. Moreover, targeted RNAses may overcome problems of toxicity and immunogenicity associated with plant- or bacterial toxin-containing immunotoxins. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Rybak, SM (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 100 TC 10 Z9 11 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD NOV PY 2001 VL 1 IS 6 BP 995 EP 1003 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 541RJ UT WOS:000174997300008 PM 11728231 ER PT J AU Virador, VM Muller, J Wu, XF Abdel-Malek, ZA Yu, ZX Ferrans, VJ Kobayashi, N Wakamatsu, K Ito, S Hammer, JA Hearing, VJ AF Virador, VM Muller, J Wu, XF Abdel-Malek, ZA Yu, ZX Ferrans, VJ Kobayashi, N Wakamatsu, K Ito, S Hammer, JA Hearing, VJ TI Influence of alpha-melanocyte-stimulating hormone and of ultraviolet radiation on the transfer of melanosomes to keratinocytes SO FASEB JOURNAL LA English DT Article DE skin color; tanning; melanosome transfer ID MOUSE MELANOCYTES; EPIDERMAL-KERATINOCYTES; IN-VITRO; PROTEIN; CELLS; EXOCYTOSIS; SYNTAXIN-4; TRANSPORT; SECRETION; SNAP-23 AB The epidermal melanin unit in human skin is composed of melanocytes and keratinocytes. Melanocytes, located in the basal layer of the epidermis, manufacture melanin-loaded organelles called melanosomes. Through their dendritic processes, melanocytes distribute melanosomes to neighboring keratinocytes, where their presence confers to the skin its characteristic color and photoprotective properties. In this study, we used murine melanocytes and keratinocytes alone and in coculture to characterize the processes involved in melanosome transfer. Ultraviolet (UV) radiation induced an accumulation of melanosomes in melanocytes, whereas treatment with alpha -melanocyte-stimulating hormone (MSH) induced exocytosis of melanosomes accompanied by ruffling of the melanocyte membrane. We found that keratinocytes phagocytose melanosomes and latex beads equally well and that this phagocytic process was increased by exposure of keratinocytes to UV radiation or to MSH. Coculture of melanocytes and keratinocytes resulted in an increase in MSH released to the medium. Gene array analysis of MSH-treated melanocytes showed up-regulation of many genes associated with exocytosis. In our studies, we never observed cytophagocytosis of melanosome-filled processes. This result, together with the other findings, suggests that a combination of signals that increase melanosome production and release by melanocytes and that stimulate phagocytosis by keratinocytes are the most relevant mechanisms involved in skin tanning. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Dermatol, Cincinnati, OH 45267 USA. NHLBI, Pathol Sect, Bethesda, MD 20892 USA. Nara Med Univ, Dept Dermatol, Kashihara, Nara 634, Japan. Fujita Hlth Univ, Sch Hlth Sci, Dept Chem, Toyoake, Aichi 4701192, Japan. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1B25, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 53 TC 6 Z9 6 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2001 VL 15 IS 13 BP 105 EP + DI 10.1096/fj.01-0518fje PG 27 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 496WR UT WOS:000172420500031 ER PT J AU Ikeyama, S Kokkonen, G Shack, S Wang, XT Holbrook, NJ AF Ikeyama, S Kokkonen, G Shack, S Wang, XT Holbrook, NJ TI Loss in oxidative stress tolerance with aging linked to reduced extracellular signal-regulated kinase and Akt kinase activities SO FASEB JOURNAL LA English DT Article DE epidermal growth factor signaling; apoptosis; Akt protein kinase ID ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR; AGE-RELATED DECLINE; EXTENDED LIFE-SPAN; CALORIC RESTRICTION; CAENORHABDITIS-ELEGANS; RAT HEPATOCYTES; CELL-SURVIVAL; EGF RECEPTOR; EXTENSION AB Oxidative stress is believed to be an important factor in the development of age-related diseases, and studies in lower organisms have established links between oxidative stress tolerance and longevity. We have hypothesized that aging is associated with a reduced ability to mount acute host defenses to oxidant injury, which increases the vulnerability of aged cells to stress. We tested this hypothesis by using primary hepatocytes from young (4-6 months) and aged (24-26 months) rats. Old hepatocytes were more sensitive to H(2)O(2)-induced apoptosis than were young cells. Lower survival was associated with reduced activations of extracellular signal-regulated kinase (ERK) and Akt kinase, both of which protect against oxidant injury. That reduced ERK and Akt activities contribute to lower survival of aged cells was supported by additional findings. First, pharmacologic inhibition of ERK and Akt activation in young cells markedly increased their sensitivity to H(2)O(2). Second, caloric restriction, which increases rodent life span and delays the onset of many age-related declines in physiologic function, prevented loss in ERK and Akt activation by H(2)O(2) and enhanced survival of old hepatocytes to levels similar to those of young cells. Strategies aimed at boosting these host responses to acute oxidant injury could have significant anti-aging benefits. C1 NIA, LCMB, Gerontol Res Ctr, IRP, Baltimore, MD 21224 USA. RP Holbrook, NJ (reprint author), NIA, LCMB, Gerontol Res Ctr, IRP, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM nikki-holbrook@nih.gov NR 35 TC 2 Z9 2 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2001 VL 15 IS 13 BP 114 EP + DI 10.1096/fj.01-0409fje PG 16 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 496WR UT WOS:000172420500037 ER PT J AU Yazawa, H Yu, ZX Takeda, K Le, Y Gong, WH Ferrans, VJ Oppenheim, JJ Li, CCH Wang, JM AF Yazawa, H Yu, ZX Takeda, K Le, Y Gong, WH Ferrans, VJ Oppenheim, JJ Li, CCH Wang, JM TI beta amyloid peptide (A beta(42)) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages SO FASEB JOURNAL LA English DT Article DE amyloid beta; Alzheimer's disease; internalization; colocalization ID DISEASE-LIKE PATHOLOGY; NECROSIS-FACTOR-ALPHA; ALZHEIMERS-DISEASE; A-BETA; SCAVENGER RECEPTOR; MICROGLIAL CELLS; MURINE MICROGLIA; HUMAN MONOCYTES; NITRIC-OXIDE; NEUROTOXICITY AB The 42 amino acid form of beta amyloid (A beta (42)) plays a pivotal role in neurotoxicity and the activation of mononuclear phagocytes in Alzheimer's disease (AD). Our recent study revealed that FPRL1, a G-protein-coupled receptor, mediates the chemotactic and activating effect of A beta (42) on mononuclear phagocytes (monocytes and microglia), suggesting that FPRL1 may be involved in the proinflammatory responses in AD. We investigated the role of FPRL1 in cellular uptake and the subsequent fibrillar formation of A beta (42) by using fluorescence confocal microscopy. We found that upon incubation with macrophages or HEK293 cells genetically engineered to express FPRL1, A beta (42) associated with FPRL1 and the A beta (42)/FPRL1 complexes were rapidly internalized into the cytoplasmic compartment. The maximal internalization of A beta (42)/FPRL1 complexes occurred by 30 min after incubation. Removal of free A beta (42) from culture supernatants at 30 min resulted in a progressive recycling of FPRL1 to the cell surface and degradation of the internalized A beta (42). However, persistent exposure of the cells to A beta (42) over 24 h resulted in retention of A beta (42)/FPRL1 complexes in the cytoplasmic compartment and the formation of Congo red positive fibrils in macrophages but not in HEK 293 cell transfected with FPRL1. These results suggest that besides mediating the proinflammatory activity of A beta (42), FPRL1 is also involved in the internalization of A beta (42), which culminates in the formation of fibrils only in macrophages. C1 NCI, Mol Immunoregulat Lab, SAIC Frederick, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Ctr Canc Res, Frederick, MD 21702 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, SAIC Frederick, Ctr Canc Res, Bldg 560,Room 31-40, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 58 TC 98 Z9 104 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2001 VL 15 IS 13 BP 2454 EP 2462 DI 10.1096/fj.01-0251com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 496WR UT WOS:000172420500015 PM 11689470 ER PT J AU Wedemeyer, H Gagneten, S Davis, A Bartenschlager, R Feinstone, S Rehermann, B AF Wedemeyer, H Gagneten, S Davis, A Bartenschlager, R Feinstone, S Rehermann, B TI Oral immunization with HCV-NS3-transformed Salmonella: Induction of HCV-specific CTL in a transgenic mouse model SO GASTROENTEROLOGY LA English DT Article ID HEPATITIS-C VIRUS; CELLULAR IMMUNE-RESPONSES; CYTOTOXIC T-LYMPHOCYTES; NONSTRUCTURAL PROTEINS; DENDRITIC CELLS; DNA VACCINATION; INFECTION; TYPHIMURIUM; VACCINES; IDENTIFICATION AB Background & Aims: The ability to induce cytotoxic T cells is considered an important feature of a candidate hepatitis C virus (HCV) vaccine. We used an oral immunization strategy with attenuated HCV-NS3-transformed Salmonella typhimurium to deliver DNA directly to the gut-associated lymphoid tissue. Methods: HLA-A2.1 transgenic mice were immunized once with transformed attenuated Salmonella. HCV-specific CD8(+) T cells were analyzed in vitro as well as in vivo by challenge of mice with recombinant HCV-NS3 vaccinia virus. Results. Salmonella (10(8) colony-forming units; 20 mug plasmid DNA) induced cytotoxic and IFN-gamma -producing CD8+ T cells specific for the immunodominant epitope NS3-1073 in 26 of 30 mice (86%) that persisted for at least 10 months. A second epitope (NS3-1169) was also recognized by cytotoxic and IFN-gamma -producing T cells, whereas a third. one (NS3-1406) stimulated IFN-gamma production without cytotoxicity. The minimal amount of: plasmid DNA required to induce CTLs was 2 ng. Upon challenge with recombinant HCV-NS3- expressing vaccinia virus, vaccinia titers were significantly lower in mice immunized with Salmonella-NS3 than in mice immunized with control Salmonella, demonstrating the in vivo function of CTLs. Conclusions:, Oral immunization with attenuated Salmonella typhimurium as a carrier for HCV DNA induces long-lasting T-cell responses. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20014 USA. Univ Mainz, Inst Virol, D-6500 Mainz, Germany. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, NIH, Bldg 10,Room 9B16,10 Ctr Dr MSC 1800, Bethesda, MD 20892 USA. RI Bartenschlager, Ralf/L-2582-2015 NR 45 TC 52 Z9 56 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2001 VL 121 IS 5 BP 1158 EP 1166 DI 10.1053/gast.2001.29311 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 487RY UT WOS:000171890100020 PM 11677208 ER PT J AU Thomson, M Nascimbeni, M Gonzales, S Murthy, KK Rehermann, B Liang, TJ AF Thomson, M Nascimbeni, M Gonzales, S Murthy, KK Rehermann, B Liang, TJ TI Emergence of a distinct pattern of viral mutations in chimpanzees infected with a homogeneous inoculum of hepatitis C virus SO GASTROENTEROLOGY LA English DT Article ID MOLECULAR CLONE; GENOTYPE 1B; CDNA CLONE; RNA; GENOME; TRANSLATION; TRANSCRIPTS; INITIATION; STABILITY; PROTEIN AB Background & Aims: Prospective, long-term study of viral evolution and immunologic responses in chimpanzees infected with a homogeneous hepatitis C virus (HCV) population is crucial in understanding the pathogenesis of HCV-host interactions. Methods: A molecular clone was constructed of HCV genotype 1b and RNA transcribed from this clone inoculated intrahepatically into chimpanzee X0142. Serum was taken from X0142 at week 2 and inoculated intravenously into a second chimpanzee (X0234). Detailed virologic, serologic, and immunologic, analyses of these 2 chimpanzees were, performed. Results. Both chimpanzees developed persistent viremia, with titers of 10(3) to :10(5) genomes/mL, for 80 weeks (X0142) and 55 weeks (X0234) of followup. A late antibody response against the nonstructural proteins and a weak, transient T-helper proliferative response were detected in both animals. In X0142, 25 mutations emerged in the virus population by week 78 and 15 in X0234 by week 35. A relatively large proportion of mutations affecting protein sequences appeared in the NS5A gene (33% in X0142 and X0234 combined), and 5 mutations were common to both chimpanzees. Conclusions. In this long-term study of the molecular evolution of HCV genotype lb from a cloned source, the appearance of a distinct pattern of mutations is suggestive of an adaptive response of HCV in vivo. In addition, a limited virus-specific immunity may contribute to HCV persistence. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, Bldg 10,Room 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HB-27091] NR 26 TC 45 Z9 46 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2001 VL 121 IS 5 BP 1226 EP 1233 DI 10.1053/gast.2001.28669 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 487RY UT WOS:000171890100028 PM 11677216 ER PT J AU Knopf, KB Warren, JL Feuer, EJ Brown, ML AF Knopf, KB Warren, JL Feuer, EJ Brown, ML TI Bowel surveillance patterns after a diagnosis of colorectal cancer in Medicare beneficiaries SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 19-23, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Soc Clin Oncol ID FOLLOW-UP; COLON-CANCER; SURGERY; GUIDELINES; CARCINOMA; RESECTION; STRATEGIES; RECURRENCE; PHYSICIANS; RATES AB Background: Postoperative colon surveillance has been recommended for patients with a diagnosis of local/regional colorectal cancer. The extent to which these recommendations are followed in practice is poorly characterized. Patterns of surveillance after surgery for colorectal cancer were determined by using a large population-based database. Methods: This is a retrospective cohort study with cancer registry data linked to Medicare claims. Identified were 52,283 patients treated for local/regional colorectal cancer between 1986 and 1996, and surveillance patterns through 1998 were determined. Surveillance patterns were analyzed by using survival analysis and by computing the proportion of surviving patients who underwent procedures during 4 time periods after treatment: 2 to 14 months, 15 to 50 months, 51 to 86 months and more than 87 months. Results: Median times to first through fifth surveillance events were 20,14,15,15, and 15 months, respectively. For 17% of the cohort there was no surveillance event. Younger patients were more likely to undergo surveillance. Surveillance patterns were not affected by stage. The proportions of the cohort that underwent no surveillance during the 4 respective time periods were 54%, 52%, 60%, and 69%. The percentages of patients who underwent surveillance annually or more frequently in the latter 3 time periods, respectively, were 19%, 10%, and 5%, or 11% overall, treating the data for the 3 events as a whole. Over the period from 1986 to 1998, the proportion of patients who had no surveillance procedures gradually decreased, whereas the proportion of those who underwent procedures annually or more frequently remained relatively constant. Conclusions: During the period from 1986 to 1998 there was low utilization of postdiagnosis colon surveillance in a substantial proportion of elderly patients with a diagnosis of local/regional colorectal cancer. Over time there was a trend toward increasing receipt of any surveillance procedures. The percentages of patients undergoing surveillance annually or more frequently did not change between earlier and later periods. C1 NCI, Hlth Serv & Econ Branch, Appl Res Program, DCCPS,NIH, Bethesda, MD 20892 USA. RP Knopf, KB (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, DCCPS,NIH, EPN 4009A,6130 Execut Blvd MSC 7344, Bethesda, MD 20892 USA. NR 29 TC 38 Z9 39 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2001 VL 54 IS 5 BP 563 EP 571 DI 10.1067/mge.2001.118949 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 488HW UT WOS:000171922700005 PM 11677471 ER PT J AU Pugliese, V Pujic, N Saccomanno, S Gatteschi, B Pera, C Aste, H Ferrara, GB Nicolo, G AF Pugliese, V Pujic, N Saccomanno, S Gatteschi, B Pera, C Aste, H Ferrara, GB Nicolo, G TI Pancreatic intraductal sampling during ERCP in patients with chronic pancreatitis and pancreatic cancer: cytologic studies and k-ras-2 codon 12 molecular analysis in 47 cases SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID RETROGRADE BRUSH CYTOLOGY; K-RAS GENES; BILE-DUCT; DIAGNOSIS; STRICTURES; BILIARY; JUICE; RISK; ASPIRATION; CARCINOMA AB Background: A preoperative tissue diagnosis of pancreatic cancer is desirable but difficult to obtain. Methods: Pancreatic brush cytology, salvage cytology, and collection of pancreatic juice were attempted prospectively during ERCP in 34 patients with pancreatic cancer and 11 with chronic pancreatitis. K-ras-2 codon 12 was analyzed for presence and type of point mutations. Results: Brush cytology coupled with salvage cytology had a sensitivity of 74%. The addition of cytologic analysis of pancreatic juice did not substantially improve sensitivity (76%). K-ras-2 was mutated in both cancer (87%) and pancreatitis (40%). The specificity for cytology was 100% and for K-ras-2 mutations 60%. Combining cytology with mutation analysis increased sensitivity to 93% but reduced the positive predictive value. The negative predictive value never exceeded 75%. None of the patients with chronic pancreatitis had cancer develop (median follow-up 60 months). Conclusions: Pancreatic ductal brushing with salvage cytology is useful in the diagnosis of cancer, whereas cytologic analysis of pancreatic juice can be abandoned. At present, K-ras-2 mutation is not useful for differentiating pancreatic cancer from chronic pancreatitis or the identification of patients with chronic pancreatitis at risk for malignant transformation. C1 Univ Genoa, Dept Oncol, Ctr Gastrointestinal Endoscopy, I-16132 Genoa, Italy. Univ Genoa, Dept Biol, I-16132 Genoa, Italy. Univ Genoa, Dept Genet, I-16132 Genoa, Italy. Natl Canc Inst, Serv Digest Endoscopy & Gastroenterol, Genoa, Italy. Natl Canc Inst, Dept Pathol, Genoa, Italy. Natl Canc Inst, Dept Immunogenet, Genoa, Italy. RP Pugliese, V (reprint author), Univ Genoa, Dept Oncol, Ctr Gastrointestinal Endoscopy, Largo R Benzi 10, I-16132 Genoa, Italy. NR 37 TC 54 Z9 54 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2001 VL 54 IS 5 BP 595 EP 599 DI 10.1067/mge.2001.119220 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 488HW UT WOS:000171922700009 PM 11677475 ER PT J AU Auroy, S Avril, MF Chompret, A Pham, D Goldstein, AM Bianchi-Scarra, G Frebourg, T Joly, P Spatz, A Rubino, C Demenais, F Bressac-de Paillerets, B AF Auroy, S Avril, MF Chompret, A Pham, D Goldstein, AM Bianchi-Scarra, G Frebourg, T Joly, P Spatz, A Rubino, C Demenais, F Bressac-de Paillerets, B CA French Hereditary Melanoma Study G TI Sporadic multiple primary melanoma cases: CDKN2A germline mutations with a founder effect SO GENES CHROMOSOMES & CANCER LA English DT Article ID TUMOR-SUPPRESSOR P16(INK4A); CYCLIN-DEPENDENT KINASE-4; FAMILIAL MELANOMA; SUSCEPTIBILITY LOCUS; PRONE FAMILIES; P16 GENE; INHIBITION; CDK4; P16/CDKN2; DELETIONS AB Multiple primary cancers are one of the hallmarks of inherited predisposition. Outside the familial context, multiple primary tumors could be related either to germline de novo mutations or to low-penetrance mutations, in predisposing genes. We selected 100 patients who displayed multiple primary melanoma (MPM) without any known melanoma cases recorded within their families and looked for germline mutations in the two melanoma-predisposing genes identified to date, CDKN2A and CDK4 exon 2. Nine patients (9%) had germline mutations in CDKN2A, whereas none carried germline mutations in exon 2 of CDK4. Seven cases displayed a recurrent missense mutation, G101W, already described in more than 20 melanoma-prone families; one case carried a missense mutation never reported to date (PI 14S), and the last case was a carrier of a 6 bp insertion at nucleotide 57 resulting in a duplication of codons 18 and 19. To ascertain whether the G101W was a mutational hot spot for de novo mutations or a common founder mutation, we genotyped eight microsatellite markers flanking the CDKN2A gene. After allowing for recombination over time, haplotype sharing provided evidence for an original G101W mutation common to 6 out of 7 sporadic MPM cases. Therefore, it can be concluded that de novo germline CDKN2A mutations associated with MPM are rare. (C) 2001 Wiley-Liss, Inc. C1 Inst Gustave Roussy, Serv Genet, F-94805 Villejuif, France. Inst Gustave Roussy, Serv Dermatol, F-94805 Villejuif, France. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Univ Genoa, Dept Oncol Biol & Genet, Genoa, Italy. IFMRP, INSERM EP19906, Fac Med & Pharm, Rouen, France. CHU Charles Nicolle, Serv Dermatol, Rouen, France. Inst Gustave Roussy, Dept Anatomopathol, Villejuif, France. Hop St Louis, INSERM EPI 00 06, Paris, France. RP Bressac-de Paillerets, B (reprint author), Inst Gustave Roussy, Serv Genet, 39 Rue Camille Desmoulins, F-94805 Villejuif, France. RI Bianchi Scarra, Giovanna/G-8933-2014; Demenais, Florence/G-3298-2013 OI Bianchi Scarra, Giovanna/0000-0002-6127-1192; Demenais, Florence/0000-0001-8361-0936 NR 37 TC 50 Z9 51 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD NOV PY 2001 VL 32 IS 3 BP 195 EP 202 DI 10.1002/gcc.1183 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 479UQ UT WOS:000171422300001 PM 11579459 ER PT J AU Gahl, WA AF Gahl, WA TI Genotypes and phenotypes SO GENETICS IN MEDICINE LA English DT Editorial Material ID CYSTINOSIS C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV-DEC PY 2001 VL 3 IS 6 BP 385 EP 386 DI 10.1097/00125817-200111000-00001 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 497LT UT WOS:000172457500001 PM 11715000 ER PT J AU Sano, Y Shimada, T Nakashima, H Nicholson, RH Eliason, JF Kocarek, TA Ko, MSH AF Sano, Y Shimada, T Nakashima, H Nicholson, RH Eliason, JF Kocarek, TA Ko, MSH TI Random monoallelic expression of three genes clustered within 60 kb of mouse t complex genomic DNA SO GENOME RESEARCH LA English DT Article ID X-LINKED GENE; CLEIDOCRANIAL DYSPLASIA; ALLELIC EXCLUSION; CELL DEVELOPMENT; TME LOCUS; CHROMOSOME; TRANSCRIPTION; INACTIVATION; RECEPTOR; BINDING AB Mammals achieve gene dosage control by (1) random X-chromosome inactivation in females, (2) parental origin-specific imprinting of selected autosomal genes, and (3) random autosomal inactivation. Genes belonging to the third category of epigenetic phenomenon are just now emerging, with only six identified so far. Here we report three additional genes, Nubp2, Igfals, and Jsap1, that show 50%-methylated CpG sites by Southern blot analyses and primarily monoallelic expression in single-cell allele-specific RT-PCP analysis of bone marrow stromal cells and hepatocytes. Furthermore, we show that, in contrast to X inactivation, alleles can switch between active and inactive states during the formation of daughter cells. These three genes are the first in their category to exist as a tight cluster, in the proximal region of mouse chromosome 17, providing a thus far unique example of a region of autosomal random monoallelic expression. C1 NIH, NIA, Dev Genom & Aging Sect, Genet Lab, Baltimore, MD 21224 USA. Keio Univ, Sch Med, Dept Prevent Med & Publ Hlth, Tokyo 160, Japan. Wayne State Univ, Dept Sci Biol, Detroit, MI 48201 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Inst Chem Toxicol, Detroit, MI 48201 USA. RP Ko, MSH (reprint author), NIH, NIA, Dev Genom & Aging Sect, Genet Lab, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU NICHD NIH HHS [R01 HD-32248] NR 55 TC 30 Z9 31 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2001 VL 11 IS 11 BP 1833 EP 1841 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 491QZ UT WOS:000172121300007 PM 11691847 ER PT J AU Wheelan, SJ Church, DM Ostell, JM AF Wheelan, SJ Church, DM Ostell, JM TI Spidey: A tool for mRNA-to-genomic alignments SO GENOME RESEARCH LA English DT Article ID PROGRAM; DNA AB We have developed a computer program that aligns spliced sequences to genomic Sequences, using local alignment algorithms and heuristics to Put together a global spliced alignment. Spidey can produce reliable alignments quickly, even when confronted with noise from alternative splicing, polymorphisms, Sequencing errors, or evolutionary divergence. We show how Spidey was used to align reference sequences to known genomic sequences and then to the draft human genome, to align mRNAs to gene clusters, and to align mouse mRNAs to human genomic sequence. We compared Spidey to two other spliced alignment programs; Spidey generally performed quite well in a very reasonable amount of time. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. RP Wheelan, SJ (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20894 USA. EM wheelan@ncbi.nlm.nih.gov NR 5 TC 226 Z9 243 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2001 VL 11 IS 11 BP 1952 EP 1957 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 491QZ UT WOS:000172121300020 PM 11691860 ER PT J AU Nyholm, PG Mulard, LA Miller, CE Lew, T Olin, R Glaudemans, CPJ AF Nyholm, PG Mulard, LA Miller, CE Lew, T Olin, R Glaudemans, CPJ TI Conformation of the O-specific polysaccharide of Shigella dysenteriae type 1: molecular modeling shows a helical structure with efficient exposure of the antigenic determinant alpha-L-Rhap-(1 -> 2)-alpha-D-Galp SO GLYCOBIOLOGY LA English DT Article DE conformation; molecular mechanics; molecular modeling; O-antigen; Shigella ID NUCLEAR-MAGNETIC-RESONANCE; CELL-WALL POLYSACCHARIDE; STREPTOCOCCUS GROUP-A; MM3 FORCE-FIELD; NMR-SPECTROSCOPY; TETRASACCHARIDE SEQUENCES; OLIGOSACCHARIDES; TRISACCHARIDE; MECHANICS; DISACCHARIDE AB The O-specific polysaccharide of Shigella dysenteriae type 1, which has the repeating tetrasaccharide unit -->3)-alpha -L-Rhap-(1-->3)-alpha -L-Rhap-(1 --> 2)-alpha -D-Galp-(1 -->3)-alpha -D-GlcNAcp-(1--> (A-B-C-D), is a major virulence factor, and it is believed that antibodies against this polysaccharide confer protection to the host. The conformational properties of fragments of this O-antigen were explored using systematic search with a modified HSEA method (GLYCAN) and with molecular mechanics MM3(96). The results show that the alpha -D-Gal-(1-->3)-alpha -D-GlcNAc linkage adopts two favored conformations, phi/psi approximate to -40 degrees/-30 degrees (I) and = 15 degrees /30 degrees (II), whereas the other glycosidic linkages only have a single favored phi/psi conformational range. MM3 indicates that the trisaccharide B-C-D and tetrasaccharides containing the B-C-D moiety exist as two different conformers, distinguished by the conformations I and II of the C-D linkage. For the pentasaccharide A-B-C-D-A' and longer fragments, the calculations show preference for the C-D conformation II. These results can explain previously reported nuclear magnetic resonance data. The pentasaccharide in its favored conformation It is sharply bent, with the galactose residue exposed at the vertex. This hairpin conformation of the pentasaccharide was successfully docked with the binding site of a monoclonal IgM antibody (E3707 E9) that had been homology modeled from known crystal structures. For fragments made of repetitive tetrasaccharide units, the hairpin conformation leads to a left-handed helical structure with the galactose residues protruding radially at the helix surface. This arrangement results in a pronounced exposure of the galactose and also the adjacent rhamnose in each repeating unit, which is consistent with the known role of the as alpha -L-Rhap-(1 -->2)-alpha -D-Galp moiety as a major antigenic epitope of this O-specific polysaccharide. C1 Univ Gothenburg, Dept Med Biochem, S-40530 Gothenburg, Sweden. Univ Gothenburg, Ctr Struct Biol, S-40530 Gothenburg, Sweden. Inst Pasteur, Unite Chim Organ, F-75724 Paris 15, France. NIDDK, Sect Carbohydrates, NIH, Bethesda, MD 20892 USA. Univ Toronto, Dept Med Genet, Toronto, ON M5S 1A8, Canada. RP Nyholm, PG (reprint author), Univ Gothenburg, Dept Med Biochem, Medicinaregatan 7, S-40530 Gothenburg, Sweden. NR 37 TC 11 Z9 12 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2001 VL 11 IS 11 BP 945 EP 955 DI 10.1093/glycob/11.11.945 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 506RX UT WOS:000172986500002 PM 11744629 ER PT J AU Michener, CM Simon, NL AF Michener, CM Simon, NL TI Ovarian conservation in a woman of reproductive age with mullerian adenosarcoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE mullerian adenosarcoma; uterine sarcoma; ovarian conservation ID GYNECOLOGIC-ONCOLOGY-GROUP; CLINICOPATHOLOGICAL ANALYSIS; UTERUS AB Background. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is generally considered optimal therapy for patients with uterine sarcomas. Local resection of the tumor or hysterectomy with ovarian conservation has been used in only a small number of patients. Recurrence risk in women undergoing ovarian-sparing surgery for mullerian adenosarcomas can be difficult to evaluate due to the paucity of literature in this area. We present a reproductive-age woman with a mullerian adenosarcoma and review the literature on conservative surgical management of this class of tumors. Case. A 25-year-old nulligravida was diagnosed with a uterine adenosarcoma and the question of conservative surgical therapy arose. Following a literature review, discussion with the patient led to the decision for ovarian preservation at the time of hysterectomy. The pelvis and abdomen were grossly free of metastatic disease at laparotomy and all tumor was confined to the uterus on pathologic examination. She is free of disease 36 months postoperatively and is now considering in vitro fertilization using a surrogate. Conclusion. Ovarian conservation can probably be offered safely in carefully selected women of reproductive age with mullerian adenosarcomas. (C) 2001 Academic Press. C1 NCI, Dept Pathol, Sect Mol Signaling, Bethesda, MD 20892 USA. Bethesda Hosp, Dept Obstet & Gynecol, Cincinnati, OH 45242 USA. RP Michener, CM (reprint author), NCI, Dept Pathol, Sect Mol Signaling, Bldg 10,Rm 2A33, Bethesda, MD 20892 USA. NR 17 TC 18 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2001 VL 83 IS 2 BP 424 EP 427 DI 10.1006/gyno.2001.6398 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 490JW UT WOS:000172049600043 PM 11606111 ER PT J AU Messick, K Sanders, JC Goedert, JJ Eyster, ME AF Messick, K Sanders, JC Goedert, JJ Eyster, ME TI Hepatitis C viral clearance and antibody reactivity patterns in persons with haemophilia and other congenital bleeding disorders SO HAEMOPHILIA LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Gastroenterological Association CY MAY 21-24, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Gastroenterol Assoc DE haemophilia; HCV RNA; hepatitis C; HIV coinfection; RIBA patterns; viral clearance ID HUMAN-IMMUNODEFICIENCY-VIRUS; NON-B HEPATITIS; NATURAL-HISTORY; LIVER-DISEASE; HCV INFECTION; FACTOR-VIII; RNA LEVELS; HEMOPHILIACS; PREVALENCE; TRANSFUSION AB We studied hepatitis C virus (HCV) clearance and antibody reactivity patterns in a cohort of 100 haemophiliacs exposed to unsterilized blood products, of whom 25 were antiHCV negative and 75 were antiHCV positive [49 human immunodeficiency virus (HIV) negative and 26 HIV positive]. HCV RNA was measured by the 2.0 bDNA assay and an 'in-house' polymerase chain, reaction assay. Antibody reactivity patterns were examined using a recombinant immunoblot assay (RIBA). Prior HCV infection was found in two (8%) of 25 antiHCV negative patients. HCV viraemia persisted in all 26 antiHCV+ patients who were coinfected with HIV. HCV RNA clearance was found in 12 (25%) of 49 antiHCV+, HIV- patients. Viral clearance was associated with younger current age (P < 0.01) and age at infection (P < 0.001), but not with duration of infection or with dose or frequency of clotting factor use. RIBA ratios reflecting an index of each patient's overall reactivity to four HCV epitopes were significantly lower in those. with viral clearance (P < 0.0001). Over a period of 15 years, those with viral clearance demonstrated significant loss of reactivity to the NS3, NS4 and NS5 epitopes, while those with viral persistence demonstrated relatively stable reactivities to all epitopes. We conclude that spontaneous HCV RNA clearance in haemophiliacs is age-related and is unlikely to occur in those coinfected with HIV. The loss of antibody reactivity for some epitopes, especially c22 (core), may be a marker for the natural resolution of chronic HCV infection. C1 Penn State Univ, Coll Med, Dept Med, Hershey, PA USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Eyster, ME (reprint author), Milton S Hershey Med Ctr, Div Hematol Oncol, POB 850,H046, Hershey, PA 17033 USA. NR 26 TC 30 Z9 31 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD NOV PY 2001 VL 7 IS 6 BP 568 EP 574 DI 10.1046/j.1365-2516.2001.00559.x PG 7 WC Hematology SC Hematology GA 511CM UT WOS:000173247100006 PM 11851755 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Relationship of serum leptin concentration and other measures of adiposity with gallbladder disease SO HEPATOLOGY LA English DT Article ID REGIONAL FAT DISTRIBUTION; GALLSTONE DISEASE; GLUCOSE-TOLERANCE; UNITED-STATES; OBESE HUMANS; JAPANESE MEN; WEIGHT-LOSS; POPULATION; INSULIN; PREVALENCE AB Obesity increases the risk of gallstones, especially in women. Most gallbladder disease studies have used body mass index (BMI) as a measure of overall adiposity, although BMI does not distinguish between fat and lean body mass. Central adiposity may also increase gallstone risk, although this is less well studied. Leptin is a peptide whose serum concentration is highly correlated with total body fat mass. We examined the relationship of gallbladder disease with anthropometric measures and serum leptin concentration in a large, national, population-based study. A total of 13,962 adult participants in the Third National Health and Nutrition Examination Survey underwent gallbladder ultrasonography and anthropometric measurements of BMI, body circumferences, and skinfold thicknesses, and a random subgroup of 5,568 had measures of fasting serum leptin concentrations. Gallstone-associated gallbladder disease was defined as ultrasound-documented gallstones or evidence of cholecystectomy. When controlling for BMI and other gallbladder disease risk factors in multivariate analysis, a test for trend for increasing waist-to-hip circumference ratio and risk of gallbladder disease was statistically significant among women (P=.043) and men (P=.007). BMI remained strongly associated with gallbladder disease among women (P < .001), but was unrelated among men (P=.46). Leptin concentration was associated with gallbladder disease in both sexes (P < .001), but not after controlling for BMI and waist-to-hip circumference in either women (P=.29) or men (P=.65). In conclusion, waist-to-hip circumference ratio was related to gallbladder disease among women and men. Serum leptin concentration was not a better predictor of gallbladder disease than anthropometry. C1 Social & Sci Syst Inc, Silver Spring, MD 20910 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave, Silver Spring, MD 20910 USA. FU NIDDK NIH HHS [N01-DK-6-2220] NR 34 TC 24 Z9 26 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2001 VL 34 IS 5 BP 877 EP 883 DI 10.1053/jhep.2001.29005 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 487HN UT WOS:000171868600003 PM 11679957 ER PT J AU Yin, M Gabele, E Wheeler, MD Connor, H Bradford, BU Dikalova, A Rusyn, I Mason, R Thurman, RG AF Yin, M Gabele, E Wheeler, MD Connor, H Bradford, BU Dikalova, A Rusyn, I Mason, R Thurman, RG TI Alcohol-induced free radicals in mice: Direct toxicants or signaling molecules? SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INDUCED LIVER-INJURY; KUPFFER CELLS; FACTOR-ALPHA; HYDROXYL RADICALS; AQUEOUS-SOLUTION; KAPPA-B; ETHANOL; RAT; DISEASE AB Tumor necrosis factor a (TNF-a) and free radicals are produced in early alcohol-induced liver injury. Recently, pathology caused by alcohol was blocked nearly completely in tumor necrosis factor a receptor 1 (TNF-RI) knockout mice. With this model, it is now possible to evaluate whether free radicals are directly toxic or act as redox regulators of TNF-a production. Specifically, if free radicals were directly toxic, a parallel decrease in free radicals and pathology in TNF-R1 knockout mice would be predicted. If they only affect TNF-a production, radicals would be expected to remain high while pathology is diminished. Accordingly, free radical production in TNF-RI knockout mice was studied here. The enteral alcohol delivery model used mice lacking TNF-R1 (p55) and wild-type control C57B1/6J mice. Animals received a liquid diet continuously with either ethanol or isocaloric maltose-dextrin as control for 4 weeks. Urine ethanol levels fluctuated from 10 to 500 mg/dL in a cyclic pattern in mice receiving ethanol. Ethanol elevated liver:body weight ratios, serum alanine transaminase (ALT) levels, and pathology scores in wild-type mice. These parameters were blunted nearly completely in TNF-R1 knockout mice. Ethanol treatment increased free radical production in wild-type mice compared with animals fed a high-fat control diet. There were no differences in intensity of free radical signals regardless of the presence or absence of TNF-RI; however, pathology differed markedly between these groups. These findings are consistent with the hypothesis that free radicals act as redox signals for TNF-a production and do not directly damage cells in early alcohol-induced hepatic injury. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Gabele, E (reprint author), Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. RI Rusyn, Ivan/S-2426-2016 NR 43 TC 51 Z9 53 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2001 VL 34 IS 5 BP 935 EP 942 DI 10.1053/jhep.2001.28888 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 487HN UT WOS:000171868600010 PM 11679964 ER PT J AU Liburd, N Ghosh, M Riazuddin, S Naz, S Khan, S Ahmed, Z Riazuddin, S Liang, Y Menon, PSN Smith, T Smith, ACM Chen, KS Lupski, JR Wilcox, ER Potocki, L Friedman, TB AF Liburd, N Ghosh, M Riazuddin, S Naz, S Khan, S Ahmed, Z Riazuddin, S Liang, Y Menon, PSN Smith, T Smith, ACM Chen, KS Lupski, JR Wilcox, ER Potocki, L Friedman, TB TI Novel mutations of MYO15A associated with profound deafness in consanguineous families and moderately severe hearing loss in a patient with Smith-Magenis syndrome SO HUMAN GENETICS LA English DT Article ID UNCONVENTIONAL MYOSIN; INTERSTITIAL DELETION; DOMINANT DEAFNESS; HAIR-CELLS; GENE; DFNB3; SHAKER-2; (17)(P11.2P11.2); MEMBRANE; LINKAGE AB Mutations in myosin XVA are responsible for the shaker 2 (sh2) phenotype in mice and nonsyndromic autosomal recessive profound hearing loss DFNB3 on chromosome 17p 11.2. We have ascertained seven families with profound congenital hearing loss from Pakistan and India with evidence of linkage to DFNB3 at 17p11.2. We report three novel homozygous mutations in MYO15A segregating in three of these families. In addition, one hemizygous missense mutation of MYO15A was found in one of eight Smith-Magenis syndrome (del(17)p11.2) patients from North America who had moderately severe sensorineural hearing loss. C1 Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, Rockville, MD 20850 USA. All India Inst Med Sci, Dept Pediat, Genet Unit, New Delhi, India. Ctr Excellence Mol Biol, Lahore, Pakistan. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Texas Childrens Hosp, Houston, TX 77030 USA. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Genet Mol Lab, NIH, 5 Res Court,Room 2A-015, Rockville, MD 20850 USA. RI Chen, Ken-Shiung/A-2204-2011; OI Naz, Sadaf/0000-0002-1912-0235 FU NCI NIH HHS [P01CA75719]; NCRR NIH HHS [M01RR00188]; NICHD NIH HHS [HD94021, K08HD01149]; NIDCD NIH HHS [1 Z01 DC00039-04, 1 Z01 DC00035-04] NR 33 TC 72 Z9 77 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2001 VL 109 IS 5 BP 535 EP 541 DI 10.1007/s004390100604 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 498QM UT WOS:000172522000009 PM 11735029 ER PT J AU Otsuki, T Furukawa, Y Ikeda, K Endo, H Yamashita, T Shinohara, A Iwamatsu, A Ozawa, K Liu, JM AF Otsuki, T Furukawa, Y Ikeda, K Endo, H Yamashita, T Shinohara, A Iwamatsu, A Ozawa, K Liu, JM TI Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex SO HUMAN MOLECULAR GENETICS LA English DT Article ID CELL-CYCLE ARREST; SWI-SNF COMPLEX; GROUP C PROTEIN; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL ACTIVATORS; COMPLEMENTATION ANALYSIS; GLUCOCORTICOID-RECEPTOR; NUCLEAR ACCUMULATION; POSITIONAL CLONING; ALKYLATING-AGENTS AB Fanconi anemia (FA) is a genetic disorder that predisposes to hematopoietic failure, birth defects and cancer. We identified an interaction between the FA protein, FANCA andbrm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase activity. FANCA was demonstrated to associate with the endogenous SWI/SNF complex. We also found a significant increase in the molecular chaperone, glucose-regulated protein 94 (GRP94) among BRG1-associated factors isolated from a FANCA-mutant cell line, which was not seen in either a normal control cell line or the mutant line complemented by wild-type FANCA. Despite this specific difference, FANCA did not appear to be absolutely required for in vitro chromatin remodeling. Finally, we demonstrated co-localization in the nucleus between transfected FANCA and BRG1. The physiological action of FANCA on the SWI/SNF complex remains to be clarified, but our work suggests that FANCA may recruit the SWI/SNF complex to target genes, thereby enabling coupled nuclear functions such as transcription and DNA repair. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Jichi Med Sch, Dept Biochem, Minami Kawachi, Tochigi 3290498, Japan. Jichi Med Sch, Dept Biol, Minami Kawachi, Tochigi 3290498, Japan. Jichi Med Sch, Ctr Mol Med, Dept Hematol, Minami Kawachi, Tochigi 3290498, Japan. Univ Tokyo, Inst Med Sci, Div Genet Diag, Minato Ku, Tokyo 108, Japan. Kirin Brewery Co Ltd, Cent Labs Key Technol, Sect Prot Chem, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. RP Liu, JM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 74 TC 58 Z9 58 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2001 VL 10 IS 23 BP 2651 EP 2660 DI 10.1093/hmg/10.23.2651 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 497GE UT WOS:000172446400006 PM 11726552 ER PT J AU Kondrashov, FA Koonin, EV AF Kondrashov, FA Koonin, EV TI Origin of alternative splicing by tandem exon duplication SO HUMAN MOLECULAR GENETICS LA English DT Article ID DROSOPHILA-MELANOGASTER; GENE DUPLICATION; BINDING-PROTEIN; NEW-GENERATION; MESSENGER-RNA; SHORT ISOFORM; EXPRESSION; SUBUNIT; IDENTIFICATION; ORGANIZATION AB Genes with new functions often evolve by gene duplication. Alternative splicing is another means of evolutionary innovation in eukaryotes, which allows a single gene to encode functionally diverse proteins. We investigate a connection between these two evolutionary phenomena. For similar to 10% of the described cases of substitution alternative splicing, such that either one or another amino acid sequence is included into the protein, evidence of origin by tandem exon duplication was found. This is a conservative estimate because alternative exons are typically short and, on many occasions, duplicates may have diverged beyond recognition. Dating exon duplications through a combination of the available experimental data on alternative splicing in orthologous genes from different species and computational analysis indicates that most of the duplications antedate at least the radiation of mammalian orders or even the radiation of vertebrate classes. At present, tandem exon duplication is the only mechanism of evolution of substitution alternative splicing that can be specifically demonstrated. Along with gene duplication, this could be a major route for generating functional diversity during evolution of multicellular eukaryotes. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 53 TC 95 Z9 99 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 1 PY 2001 VL 10 IS 23 BP 2661 EP 2669 DI 10.1093/hmg/10.23.2661 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 497GE UT WOS:000172446400007 PM 11726553 ER PT J AU Dunson, DB Sinai, I Colombo, B AF Dunson, DB Sinai, I Colombo, B TI The relationship between cervical secretions and the daily probabilities of pregnancy: effectiveness of the TwoDay Algorithm SO HUMAN REPRODUCTION LA English DT Article DE Bayesian; cervical secretions; fecundability; fertile interval; natural family planning ID POSTERIOR DISTRIBUTIONS; HUMAN-FERTILITY; MARKOV-CHAINS; OVULATION; INTERCOURSE; FAILURE; MODELS AB BACKGROUND: The TwoDay Algorithm is a simple method for identifying the fertile window. It classifies a day as fertile if cervical secretions are present on that day or were present on the day before. This approach may be an effective alternative to the ovulation and symptothermal methods for populations and programmes that find current natural family planning methods difficult to implement. METHODS: We used data on secretions from a large multinational European fecundability study to assess the relationship between the days predicted to be potentially fertile by the TwoDay Algorithm and the day-specific probabilities of pregnancy based on intercourse patterns in 434 conception cycles from the study. RESULTS: The days around ovulation that had the highest fecundability were the days most likely to be classified as fertile by the TwoDay Algorithm. In addition, intercourse on a particular day in the fertile interval was twice as likely to result in a pregnancy if cervical secretions were present on that day or the day before. CONCLUSIONS: The TwoDay Algorithm is effective, both in identifying the fertile days of the cycle and in predicting days within the fertile interval that have a high pregnancy rate. Our data provide, the first direct evidence that cervical secretions are associated with higher fecundability within the fertile window. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Georgetown Univ, Inst Reprod Hlth, Washington, DC USA. Univ Padua, Dept Stat, Padua, Italy. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233 MD A3-03, Res Triangle Pk, NC 27709 USA. NR 26 TC 33 Z9 33 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 2001 VL 16 IS 11 BP 2278 EP 2282 DI 10.1093/humrep/16.11.2278 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 491FK UT WOS:000172097200008 PM 11679504 ER PT J AU McVeigh, E Ozturk, C AF McVeigh, E Ozturk, C TI Imaging myocardial strain SO IEEE SIGNAL PROCESSING MAGAZINE LA English DT Article ID TAGGED MR-IMAGES; OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY; VENTRICULAR PACING SITES; CANINE LEFT-VENTRICLE; PHASED-ARRAY COIL; MAGNETIC-RESONANCE; SPATIAL MODULATION; DILATED CARDIOMYOPATHY; MECHANICAL ACTIVATION; CONDUCTION DELAY C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Bogazici Univ, Inst Biomed Engn, Istanbul, Turkey. RP McVeigh, E (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. RI Magazine, Signal Processing/E-9947-2015; Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 NR 73 TC 11 Z9 12 U1 1 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1053-5888 J9 IEEE SIGNAL PROC MAG JI IEEE Signal Process. Mag. PD NOV PY 2001 VL 18 IS 6 BP 44 EP 56 DI 10.1109/79.962277 PG 13 WC Engineering, Electrical & Electronic SC Engineering GA 486VC UT WOS:000171836800007 ER PT J AU Alexander, DC Pierpaoli, C Basser, PJ Gee, JC AF Alexander, DC Pierpaoli, C Basser, PJ Gee, JC TI Spatial transformations of diffusion tensor magnetic resonance images SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE diffusion tensor magnetic resonance imaging; DTI; DT-MRI; image processing; registration; spatial transformation; warp AB We address the problem of applying spatial transformations (or "image warps") to diffusion tensor magnetic resonance images. The orientational information that these images contain must be handled appropriately when they are transformed spatially during image registration. We present solutions for global transformations of three-dimensional images up to 12-parameter affine complexity and indicate how our methods can be extended for higher order transformations. Several approaches are presented and tested using synthetic data. One method, the preservation of principal direction algorithm, which takes into account shearing, stretching and rigid rotation, is shown to be the most effective. Additional registration experiments are performed on human brain data obtained from a single subject, whose head was imaged in three different orientations within the scanner. All of our methods improve the consistency between registered and target images over naive warping algorithms. C1 UCL, Dept Comp Sci, London WC1E 6BT, England. NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Alexander, DC (reprint author), UCL, Dept Comp Sci, Gower St, London WC1E 6BT, England. EM daniel.alexander@cs.ucl.ac.uk RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 FU NINDS NIH HHS [R01-NS33662] NR 22 TC 421 Z9 423 U1 1 U2 24 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD NOV PY 2001 VL 20 IS 11 BP 1131 EP 1139 DI 10.1109/42.963816 PG 9 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 488JX UT WOS:000171933000003 PM 11700739 ER PT J AU Delon, J Kaibuchi, K Germain, RN AF Delon, J Kaibuchi, K Germain, RN TI Exclusion of CD43 from the immunological synapse is mediated by phosphorylation-regulated relocation of the cytoskeletal adaptor moesin SO IMMUNITY LA English DT Article ID T-CELL ACTIVATION; EZRIN/RADIXIN/MOESIN ERM PROTEINS; RHO-ASSOCIATED KINASE; F-ACTIN BINDING; ANTIGEN RECOGNITION; FAMILY MEMBERS; B-CELLS; C-THETA; LYMPHOCYTES; RECEPTOR AB Formation of the immunological synapse requires TOR signal-dependent protein redistribution. However, the specific molecular mechanisms controlling protein relocation are not well defined. Moesin is a widely expressed phospho-protein that links many transmembrane molecules to the cortical actin cytoskeleton. Here, we demonstrate that TCR-induced exclusion of the large sialoprotein CD43 from the synapse is an active event mediated by its reversible binding to moesin. Our results also reveal that relocalization of moesin is associated with changes in the phosphorylation status of this cytoskeletal adaptor protein. Finally, these findings raise the possibility that the change in moesin localization resulting from TCR engagement modifies the overall topology of the lymphocyte membrane and facilitates molecular interactions at the site of presenting cell contact. C1 NIAID, Immunol Lab, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. Nagoya Univ, Grad Sch Med, Dept Cell Pharmacol, Aichi 4668550, Japan. RP Germain, RN (reprint author), NIAID, Immunol Lab, Lymphocyte Biol Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 52 TC 198 Z9 202 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2001 VL 15 IS 5 BP 691 EP 701 DI 10.1016/S1074-7613(01)00231-X PG 11 WC Immunology SC Immunology GA 498UE UT WOS:000172528200003 PM 11728332 ER PT J AU Betts, MR Casazza, JP Koup, RA AF Betts, MR Casazza, JP Koup, RA TI Monitoring HIV-specific CD8+T cell responses by intracellular cytokine production SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 3rd International Meeting on Immunological Correlates of Protection from HIV Infection and Disease CY NOV 30-DEC 03, 2000 CL LEVANTE, ITALY SP European Unions Qual Life & Management Living Resource Programme, NIH, Off AIDS Res, SmithKline Beecham Biol, Merck Res Labs, WHO, AIDS DE intracellular cytokine; peptide; CD8 ID ACTIVE ANTIRETROVIRAL THERAPY; CYTOTOXIC T-LYMPHOCYTES; PRIMARY INFECTION; VIRUS; VIREMIA; ESCAPE; INDIVIDUALS; SUPPRESSION; SELECTION; EFFECTOR AB Human immunodeficiency virus (HIV)-specific CD8 + T cells play an important role in controlling HIV infection. Accurate monitoring of these cells is crucial in determining the effects of HIV therapy and vaccine efficacy. Using an intracellular cytokine staining based assay, we are able to directly quantify functional HIV-specific CD8 + T cells. This assay is highly reproducible, and can be performed using both fresh and cryopreserved peripheral blood cells. Importantly, this assay can be used to examine multiple HIV-peptide epitopes simultaneously, and is independent of patient HLA haplotype. Here, we examine the HIV-specific CD8 + T cell response to 95 optimized HIV-derived cytotoxic T lymphocyte (CTL) epitopes in 21 HIV-infected patients of varying HLA haplotype, using peptide mixes and matrices. We find that when using mixes of multiple HIV peptides, the CD8 + T cell response to the mixture is equivalent to the sum of the responses to the individual peptides contained therein. Detailed comparison of the responses in patients suggests that most patients generate a diverse CD8 + T cell response, recognizing multiple HIV epitopes derived from HIV Gag, Pol, Env, or Nef. Although some patients sharing HLA alleles occasionally recognize common peptides, rarely are responses to those peptides dominant within the same group of patients. These results confirm our previous findings that the responses to single HIV-peptides are rarely representative of the entire HIV response. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Koup, RA (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 40,Room 3502,40 Convent Dr,MSC 3022, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R37 AI 35522, R01 AI 47603, U01 AI 43638] NR 19 TC 51 Z9 54 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD NOV 1 PY 2001 VL 79 IS 1-2 BP 117 EP 125 DI 10.1016/S0165-2478(01)00273-5 PG 9 WC Immunology SC Immunology GA 489PP UT WOS:000172000500017 PM 11595298 ER PT J AU Carrington, M Nelson, G O'Brien, SJ AF Carrington, M Nelson, G O'Brien, SJ TI Considering genetic profiles in functional studies of immune responsiveness to HIV-1 SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 3rd International Meeting on Immunological Correlates of Protection from HIV Infection and Disease CY NOV 30-DEC 03, 2000 CL LEVANTE, ITALY SP European Unions Qual Life & Management Living Resource Programme, NIH, Off AIDS Res, SmithKline Beecham Biol, Merck Res Labs, WHO, AIDS DE disease progression; genetic profile ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; MANNAN-BINDING-PROTEIN; CC-CHEMOKINE RECEPTOR-5; MACROPHAGE-TROPIC HIV-1; MULTICENTER AIDS COHORT; ALPHA PROMOTER REGION; DISEASE PROGRESSION; TYPE-1 INFECTION; MESSENGER-RNA AB Over the last two decades HIV-1 has spread worldwide and has now surpassed malaria as the leading cause of infectious disease mortality in adults (http://www.who.int/infectious-disease-report/pages/ch1text.html). The clinical course and outcome of HIV-1 infection are highly variable among individuals. Most individuals infected with HIV develop AIDS within 10 years. However about 1-5% remain relatively healthy for 15 years or more (long-term nonprogressors), while others progress to AIDS within the first 2-3 years after infection (rapid progressors). A small number of individuals are resistant to infection, while some individuals appear to eliminate the virus. Factors that influence susceptibility to infection and rate of disease progression are a combination of viral, host, and environmental determinants. With few exceptions, genetic resistance to infectious diseases is likely to involve a complex array of host genetic effects involving variants that have very subtle, but significant consequences on gene expression or protein function. We have gained considerable insight into the genetic effects on HIV-1 disease, yet we likely have uncovered only a fraction of the total picture. The greater our knowledge of various effects on HIV disease, the more likely we will be able to predict disease outcome on an individual-by-individual basis. While this may seem obvious, there is no standard practice of taking into account the genetic profile (i.e. genotypes at loci known to associate with rate of AIDS progression) of subjects used in functional studies of immune responsiveness to HIV-1. Here, we propose an approach for assessing overall genetic risk on an individual basis, and suggest that this information be considered when selecting comparison groups in studies of immune responses to HIV and/or in the interpretation of data derived from such studies. Published by Elsevier Science B.V. C1 Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Carrington, M (reprint author), Sci Applicat Int Corp, Intramural Res Support Program, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 133 TC 39 Z9 45 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD NOV 1 PY 2001 VL 79 IS 1-2 BP 131 EP 140 DI 10.1016/S0165-2478(01)00275-9 PG 10 WC Immunology SC Immunology GA 489PP UT WOS:000172000500019 PM 11595300 ER PT J AU Migueles, SA Connors, M AF Migueles, SA Connors, M TI Frequency and function of HIV-specific CD8(+) T cells SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 3rd International Meeting on Immunological Correlates of Protection from HIV Infection and Disease CY NOV 30-DEC 03, 2000 CL LEVANTE, ITALY SP European Unions Qual Life & Management Living Resource Programme, NIH, Off AIDS Res, SmithKline Beecham Biol, Merck Res Labs, WHO, AIDS DE CTL epitopes; tetramers; ELIspot; intracytoplasmic cytokines; long term nonprogressors ID IMMUNODEFICIENCY-VIRUS TYPE-1; LONG-TERM NONPROGRESSORS; NEUTRALIZING ANTIBODY-RESPONSES; ANTIRETROVIRAL THERAPY; LYMPHOCYTE ACTIVITY; INFECTION; PROGRESSION; DISEASE; VIREMIA; RNA AB The virus-specific CD8(+) T cell responses of 27 HIV-infected patients were studied, including a unique cohort of long term nonprogressors (LTNP) with normal CD4(+) T cell counts, low levels of plasma viral RNA, strong proliferative responses to HIV antigens and an over-representation of the HLA B*5701 class I allele. The frequencies of CD8+ T cells specific to the majority of HIV gene products were measured by flow cytometric detection of intracellular interferon-gamma (IFN-gamma) in response to HIV-vaccinia recombinant infected autologous B cells. Very high frequencies (1.4-22%) of circulating CD8(+) T cells were found to be HIV-specific and were not only found in LTNP with reduced plasma virus. No correlation was evident between the frequency of HIV-specific CD8(+) T cells and levels of plasma viremia. In each case, the vast majority of cells (up to 17.2%) responded to Gag-Pol gene products. Although similar frequencies of Gag peptide-specific CD8(+) T cells were found in LTNP and progressors by either intracellular IFN-gamma or MHC class I tetramer staining, the breadth of these responses was greater in patients with progressive HIV infection compared with the LTNP group. The frequency of CD8(+) T cells specific for a single peptide was not representative of an individual patient's total HIV-specific CD8(+) T cell response. These data demonstrate that high numbers of HIV-specific CD8(+) T cells exist even in patients with high level viremia and progressive disease. Further, they suggest that other qualitative parameters of the CD8(+) T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive infection. Published by Elsevier Science B.V. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Connors, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B-09,10 Ctr Dr MSC 1876, Bethesda, MD 20892 USA. NR 37 TC 50 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD NOV 1 PY 2001 VL 79 IS 1-2 BP 141 EP 150 DI 10.1016/S0165-2478(01)00276-0 PG 10 WC Immunology SC Immunology GA 489PP UT WOS:000172000500020 PM 11595301 ER PT J AU Mucci, N Ianni, A Ursini, CL Arzani, D Bhat, NK Navarra, P Romano-Spica, V AF Mucci, N Ianni, A Ursini, CL Arzani, D Bhat, NK Navarra, P Romano-Spica, V TI In vivo modulation of ETS genes induced by electromagnetic fields SO IN VIVO LA English DT Article DE ETS genes; T-lymphocyte; calcium ions; corticosterone; BALB/c mice ID INTRACELLULAR CALCIUM OSCILLATIONS; COLON-CANCER CELLS; MAGNETIC-FIELDS; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; RESEARCH NEEDS; T-CELLS; FREQUENCY; EXPRESSION; ACTIVATION AB We have previously shown that electromagnetic field (EMF) exposure induces ETS1 oncogene overexpression it? different cell lines. In order to investigate in vivo EMF effects, BALB/c mice were exposed at different times to 50 MHz radiation, modulated (80%) at 16 Hz. The exposed and control animals were sacrificed and the spleen excised for rt-pcr and western blot analysis. We observed an increase in ETS1 mRNA and protein expression, but a decrease in ETS2 protein levels. Preliminary results from this experimental model show in vivo evidence of the effect of EMF on ETS oncogene expression. C1 Univ Sacred Heart, Inst Hyg, I-00168 Rome, Italy. Univ Sacred Heart, Inst Pharmacol, I-00168 Rome, Italy. ISPESL, Dept Occupat Med, Rome, Italy. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp Inc, Recombinant DNA Lab, Frederick, MD 21702 USA. RP Romano-Spica, V (reprint author), Univ Sacred Heart, Inst Hyg & Publ Hlth, Lgo F Vito, I-00168 Rome, Italy. NR 40 TC 0 Z9 0 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD NOV-DEC PY 2001 VL 15 IS 6 BP 489 EP 494 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 526DJ UT WOS:000174113200007 PM 11887334 ER PT J AU Park, MK Hoffmann, KF Cheever, AW Amichay, D Wynn, TA Farber, JM AF Park, MK Hoffmann, KF Cheever, AW Amichay, D Wynn, TA Farber, JM TI Patterns of chemokine expression in models of Schistosoma mansoni inflammation and infection reveal relationships between type 1 and type 2 responses and chemokines in vivo SO INFECTION AND IMMUNITY LA English DT Article ID ELICITED GRANULOMA-FORMATION; IFN-GAMMA; T-CELLS; DIFFERENTIAL EXPRESSION; HEPATIC-FIBROSIS; EOSINOPHIL RECRUITMENT; MURINE SCHISTOSOMIASIS; MYCOBACTERIAL TYPE-1; RECEPTOR EXPRESSION; CYTOKINE RESPONSES AB To explore the roles of chemokines in type 1 and type 2 responses in vivo, we examined mRNA expression for a panel of up to 17 chemokines in experimental mouse models using Schistosoma mansoni. These studies revealed that Mig (monokine induced by gamma interferon), cytokine-responsive gene 2/10-kDa interferon-inducible protein, RANTES, lymphotactin, macrophage inflammatory protein 1 beta (MIP-1 beta), JE/monocyte chemoattractant protein 1, and MIP-2 are associated with type 1 egg-induced responses and that thymus-derived chemotactic agent 3 (TCA3), eotaxin, MIP-1 alpha, and MIP-1 gamma are associated with type 2 egg-induced responses. After cercarial infection, both type 1-associated and type 2-associated chemokines were elevated in the livers of infected mice presensitized with eggs and recombinant interieukin-12 (rIL-12), a regimen that diminishes pathology. Neutralization of IL-12 or gamma interferon during egg deposition reversed the effects of prior treatment with rIL-12, leading to a return to larger granulomas; persistently elevated expression of TCA3, eotaxin, and MIP-1 alpha; and a marked reduction in the expression of type 1-associated chemokines despite the maintenance of a dominant type 1 cytokine response in the draining lymph nodes. Our findings suggest that there are patterns of coordinate chemokine expression characteristic of type 1 and type 2 responses in vivo; that the cells recruited by a given pattern of chemokines may differ, depending on the composition of peripheral populations; and that patterns of tissue expression of chemokines may determine the character of an inflammatory response independently of the dominant pattern of differentiation of antigen-specific T cells. Our data reveal new relationships between chemokines and polarized immune responses and suggest that end organ inflammation might be altered by chemokine blockade without necessitating reversal of the phenotype of the majority of differentiated T cells. C1 NIAID, Parasit Dis Lab, Immunobiol Sect, Schistosomiasis Immunol & Pathol Unit,NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Wynn, TA (reprint author), NIAID, Parasit Dis Lab, Immunobiol Sect, Schistosomiasis Immunol & Pathol Unit,NIH, Bldg 4,Rm 126,MSC 0425, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 62 TC 34 Z9 36 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2001 VL 69 IS 11 BP 6755 EP 6768 DI 10.1128/IAI.69.11.6755-6768.2001 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 485DX UT WOS:000171739200026 PM 11598048 ER PT J AU Hertle, R Mrsny, R Fitzgerald, DJ AF Hertle, R Mrsny, R Fitzgerald, DJ TI Dual-function vaccine for Pseudomonas aeruginosa: Characterization of chimeric exotoxin A-pilin protein SO INFECTION AND IMMUNITY LA English DT Article ID RECEPTOR-BINDING DOMAIN; FIBROSIS EPITHELIAL-CELLS; TOXIN-A; CYSTIC-FIBROSIS; OUTER-MEMBRANE; CONJUGATE VACCINE; CANDIDA-ALBICANS; PILUS ADHESIN; TYPE-4 PILUS; STRAINS PAK AB Pseudomonas aeruginosa is the major infectious agent of concern for cystic fibrosis patients. Strategies to prevent colonization by this bacterium and/or neutralize its virulence factors are clearly needed. Here we characterize a dual-function vaccine designed to generate antibodies to reduce bacterial adherence and to neutralize the cytotoxic activity of exotoxin A. To construct the vaccine, key sequences from type IV pilin were inserted into a vector encoding a nontoxic (active-site deletion) version of exotoxin A. The chimeric protein, termed PE64 Delta 553pil, was expressed in Escherichia coli, refolded to a near-native conformation, and then characterized by various biochemical and immunological assays. PE64 Delta 553pil bound specifically to asialo-GM1, and, when injected into rabbits, produced antibodies that reduced bacterial adherence and neutralized the cell-killing activity of exotoxin A. Results support further evaluation of this chimeric protein as a vaccine to prevent Pseudomonas colonization in susceptible individuals. C1 NCI, Biotherapy Sect, Mol Biol Lab, CCR, Bethesda, MD 20892 USA. Genentech Inc, S San Francisco, CA 94080 USA. RP Fitzgerald, DJ (reprint author), NCI, Biotherapy Sect, Mol Biol Lab, CCR, Bldg 37,4B03,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 54 TC 21 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2001 VL 69 IS 11 BP 6962 EP 6969 DI 10.1128/IAI.69.11.6962-6969.2001 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 485DX UT WOS:000171739200049 PM 11598071 ER PT J AU Rogers, JD Palmer, RJ Kolenbrander, PE Scannapieco, FA AF Rogers, JD Palmer, RJ Kolenbrander, PE Scannapieco, FA TI Role of Streptococcus gordonii amylase-binding protein a in adhesion to hydroxyapatite, starch metabolism, and biofilm formation SO INFECTION AND IMMUNITY LA English DT Article ID SALIVARY ALPHA-AMYLASE; ORAL STREPTOCOCCI; INTRAGENERIC COAGGREGATION; DENTAL PLAQUE; DL1 CHALLIS; GENE ABPA; SURFACE; BACTERIA; SANGUIS; IDENTIFICATION AB Interactions between bacteria and salivary components are thought to be important in the establishment and ecology of the oral microflora. oz-Amylase, the predominant salivary enzyme in humans, binds to Streptococcus gordonii, a primary colonizer of the tooth. Previous studies have implicated this interaction in adhesion of the bacteria to salivary pellicles, catabolism of dietary starches, and biofilm formation. Amylase binding is mediated at least in part by the amylase-binding protein A (AbpA). To study the function of this protein, an erythromycin resistance determinant [erm(AM)] was inserted within the abpA gene of S. gordonii strains Challis and FAS4 by allelic exchange, resulting in abpA mutant strains Challis-E1 and FAS4-E1. Comparison of the wild-type and mutant strains did not reveal any significant differences in colony morphology, biochemical metabolic profiles, growth in complex or defined media, surface hydrophobicity, or coaggregation properties. Scatchard analysis of adhesion isotherms demonstrated that the wild-type strains adhered better to human parotid-saliva- and amylase-coated hydroxyapatite than did the AbpA mutants. In contrast, the mutant strains bound to whole-saliva-coated hydroxyapatite to a greater extent than did the wild-type strains. While the wild-type strains preincubated with purified salivary amylase grew well in defined medium with potato starch as the sole carbohydrate source, the AbpA mutants did not grow under the same conditions even after preincubation with amylase. In addition, the wild-type strain produced large microcolonies in a flow cell biofilm model, while the abpA mutant strains grew much more poorly and produced relatively small microcolonies. Taken together, these results suggest that AbpA of S. gordonii functions as an adhesin to amylase-coated hydroxyapatite, in salivary-amylase-mediated catabolism of dietary starches and in human saliva-supported biofilm formation by S. gordonii. C1 SUNY Buffalo, Sch Dent Med, Dept Oral Biol, Buffalo, NY 14214 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Scannapieco, FA (reprint author), SUNY Buffalo, Sch Dent Med, Dept Oral Biol, 109 Foster Hall, Buffalo, NY 14214 USA. FU NIDCR NIH HHS [DE 09838, R01 DE009838, R56 DE009838, DE 00158] NR 52 TC 48 Z9 49 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2001 VL 69 IS 11 BP 7046 EP 7056 DI 10.1128/IAI.69.11.7046-7056.2001 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 485DX UT WOS:000171739200058 PM 11598080 ER PT J AU Hayman, JR Hayes, SF Amon, J Nash, TE AF Hayman, JR Hayes, SF Amon, J Nash, TE TI Developmental expression of two spore wall proteins during maturation of the microsporidian Encephalitozoon intestinalis SO INFECTION AND IMMUNITY LA English DT Article ID AIDS PATIENTS; CHRONIC DIARRHEA; FINE-STRUCTURE; CUNICULI; MICE; PATHOGEN; IMMUNOCOMPETENT; IDENTIFICATION; INFECTIVITY; HELLEM AB Microsporidia are intracellular eukaryotes that infect many animals and cause opportunistic infections in AIDS patients. The disease is transmitted via environmentally resistant spores. Two spore wall constituents from the microsporidian Encephalitozoon intestinalis were characterized. Spore wall protein 1 (SWP1), a 50-kDa glycoprotein recognized by monoclonal antibody (MAb) 11B2, was detected in developing sporonts and at low levels on the surfaces of mature spores. In contrast, SWP2, a 150-kDa glycoprotein recognized by MAb 7G7, was detected on fully formed sporonts and was more abundant on mature spores than SWP1 Nevertheless, the SWPs appeared to be complexed on the surfaces of mature spores. SWP1 and SWP2 are similar at the DNA and protein levels and have 10 conserved cysteines. in the N-terminal domain, suggesting similar secondary structures. The C-terminal domain of SWP2 has a unique region containing 50 repeating 12- or 15-amino-acid units that lacks homology to known protein motifs. Antibodies from mice infected with E. intestinalis recognized SWP1 and SNVP2. The characterization of two immunogenic SWPs from E. intestinalis will allow the study of exospore structure and function and may lead to the development of useful tools in the diagnosis and treatment of microsporidiosis. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Hayman, JR (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room B1-06,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. NR 33 TC 40 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2001 VL 69 IS 11 BP 7057 EP 7066 DI 10.1128/IAI.69.11.7057-7066.2001 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 485DX UT WOS:000171739200059 PM 11598081 ER PT J AU Collins, GD Le, SY Zhang, KZ AF Collins, GD Le, SY Zhang, KZ TI A new algorithm for computing similarity between RNA structures SO INFORMATION SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Workshop on Biomolecular Informatics CY FEB 27-MAR 03, 2000 CL ATLANTIC CITY, NEW JERSEY DE molecular biology; RNA structures; similarity ID SECONDARY STRUCTURES AB The primary structure of a ribonucleic acid (RNA) molecule is a sequence of nucleotides (bases) over the four-letter alphabet {A, C, G, U}. The secondary or tertiary structure of an RNA is a set of base-pairs (nucleotide pairs) which form bonds between A-U and C-G. For secondary structures, these bonds have been traditionally assumed to be one-to-one and non-crossing. We consider the edit distance between two RNA structures. This is a notion of similarity, introduced in [Proceedings of the Tenth Symposium on Combinatorial Pattern Matching, Lecture Notes in Computer Science, vol. 1645, Springer, Berlin, 1999, p. 281], between two RNA molecule structures taking into account the primary, the secondary and the tertiary structures. In general this problem is NP-hard for tertiary structures. In this paper, we consider this notion under some constraints. We present an algorithm and then show how to use this algorithm for practical applications. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Western Ontario, Dept Comp Sci, London, ON N6A 5B7, Canada. NCI, Lab Expt & Comp Biol, NIH, Frederick, MD 21702 USA. RP Zhang, KZ (reprint author), Univ Western Ontario, Dept Comp Sci, London, ON N6A 5B7, Canada. NR 19 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0020-0255 J9 INFORM SCIENCES JI Inf. Sci. PD NOV PY 2001 VL 139 IS 1-2 BP 59 EP 77 DI 10.1016/S0020-0255(01)00157-8 PG 19 WC Computer Science, Information Systems SC Computer Science GA 500RV UT WOS:000172641300004 ER PT J AU Ahlers, JD Belyakov, IM Matsui, S Berzofsky, JA AF Ahlers, JD Belyakov, IM Matsui, S Berzofsky, JA TI Signals delivered through TCR instruct IL-12 receptor (IL-12R) expression: IL-12 and tumor necrosis factor-alpha synergize for IL-12R expression at low antigen dose SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cellular activation; cytokine; cytokine receptors; T lymphocyte; T(h)1/T(h)2 ID ALTERED PEPTIDE LIGANDS; PHENOTYPE DEVELOPMENT; TNF-ALPHA; TH2 CELLS; IFN-GAMMA; T-CELLS; CYTOKINE; DIFFERENTIATION; INTERLEUKIN-12; LYMPHOCYTES AB Regulation of the IL-12 receptor (IL-12R) beta2 chain has been suggested to function as a molecular switch in determining T cell phenotype. However, because most studies have been carried out under conditions in which cell proliferation was occurring, it has been difficult to distinguish between instructive and selective mechanisms in regulating this key receptor. Here, in the course of trying to understand the mechanism for synergy between IL-12 and TNF-alpha in up-regulating IFN-gamma production, we find that when the stimulus through the TCR is too weak to induce cell proliferation, which would be needed for selection, IL-12 and TNF-alpha synergize to up-regulate not only IFN-gamma, but also the IL-12R beta2 chain, which triggers IFN-gamma production. Neither cytokine alone was sufficient. This observation held true both in the absence of antigen-presenting cells (APC), when the stimulus was anti-CD3 on plastic, and in the presence of APC presenting ovalbumin peptide to TCR-transgenic T cells. In contrast, when the TCR signal was stronger, no cytokines were necessary to up-regulate the IL-12R. Our results support the strength of signal model in instructing Th phenotype, and suggest both an instructive role and, later, through the production of IFN-gamma, a selective role, of this synergistic combination of cytokines in the preferential differentiation and expansion of TO cells. C1 NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA. NR 29 TC 21 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2001 VL 13 IS 11 BP 1433 EP 1442 DI 10.1093/intimm/13.11.1433 PG 10 WC Immunology SC Immunology GA 491FY UT WOS:000172099100009 PM 11675375 ER PT J AU Pompeia, C Boaventura, MFC Curi, R AF Pompeia, C Boaventura, MFC Curi, R TI Antiapoptotic effect of dipyrone on HL-60, Jurkat and Raji cell lines submitted to UV irradiation, arachidonic acid and cycloheximide treatments SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE dipyrone; metamizol; leukocytes; apoptosis; antiapoptotic effect; cytoprotection ID APOPTOSIS; ANALGESIA; PATHWAY AB The effect of dipyrone (metamizol) on cell viability was evaluated in human leukocyte cell lines upon different apoptotic treatments: arachidonic acid (AA), cycloheximide (CHX), tumor necrosis factor (TNF) and ultraviolet (UV) irradiation, Dipyrone had a dual effect: at high concentrations (beyond 300 muM), it was cytotoxic, leading to apoptosis, whereas at lower concentrations (37.5-300 muM), it was cytoprotective, delaying the loss of membrane integrity triggered by arachidonic acid (100-200 muM) and UV irradiation and the cytotoxicity of cycloheximide (25-50 muM). No effect of dipyrone was found on TNF-induced cytotoxicity (250 ng/ml). The cytoprotective effect of dipyrone is associated with a decrease in DNA fragmentation, as assessed by electrophoresis of genomic DNA and by flow cytometry; a reduction in the percentage of condensed nuclei, as evaluated by DNA staining with Hoescht 33342 and a decrease in poly(ADP)-ribose polymerase (PARP) cleavage, as assessed by Western blotting. The cytoprotective effect of dipyrone on leukocyte apoptosis occurs at concentrations usually found for the main active metabolite of the drug and may have implications on the therapeutic and side effects caused by this agent. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Inst Deafness & Other Commun Disorders, Natl Inst Hlth USA, Bethesda, MD 20892 USA. Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Lab Cell Physiol, BR-05508900 Sao Paulo, SP, Brazil. RP Pompeia, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Natl Inst Hlth USA, Bldg 36,Rdm 5D-15,36 Convent Dr, Bethesda, MD 20892 USA. RI Curi , Rui/C-9351-2012; Cury-Boaventura, Maria Fernanda/B-3945-2012 NR 15 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD NOV PY 2001 VL 1 IS 12 BP 2173 EP 2182 DI 10.1016/S1567-5769(01)00144-8 PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 489BL UT WOS:000171972100012 PM 11710546 ER PT J AU Bornstein, MH Cote, LR AF Bornstein, MH Cote, LR TI Mother-infant interaction and acculturation: I. Behavioural comparisons in Japanese American and South American families SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID UNITED-STATES; CHILD-DEVELOPMENT; SCALE; SELF; IDENTITY; PSYCHOLOGY; AGREEMENT; CULTURE; PLAY AB This study examined similarities and differences in mothers' and infants' activities and interactions among 37 Japanese American and 40 South American dyads. Few relations between maternal acculturation level or individualism/collectivism and maternal parenting or infant behaviours emerged in either group. However, group differences were found in mothers' and infants' behaviours indicating that culture-of-origin continues to influence parenting behaviour in acculturating groups. C1 NICHHD, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov; 1c140v@nih.gov NR 93 TC 24 Z9 24 U1 3 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD NOV PY 2001 VL 25 IS 6 BP 549 EP 563 PG 15 WC Psychology, Developmental SC Psychology GA 483HX UT WOS:000171630700008 ER PT J AU Cote, LR Bornstein, MH AF Cote, LR Bornstein, MH TI Mother-infant interaction and acculturation: II. Behavioural coherence and correspondence in Japanese American and South American families SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID UNITED-STATES; NATURALISTIC EXCHANGES; SELF; METAANALYSIS; PSYCHOLOGY; ATTACHMENT; CHILDREN; CONTEXTS; CULTURE AB This study examined cultural generality and specificity in relations among and between mothers' and infants' behaviours in 37 Japanese American and 40 South American acculturating families. Few relations among mothers' behaviours emerged, except for that between mothers' social behaviour and other types of maternal behaviour, which appear to re? ect the common collectivist orientation of these two cultural groups. Few relations among infants' behaviours emerged, suggesting that there is independence and plasticity in infant behavioural organisation. Several expected relations between mothers' and infants' behaviours emerged, pointing to some universal characteristics in mother-infant interactions. C1 NICHHD, Bethesda, MD 20892 USA. RP Cote, LR (reprint author), NICHHD, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 71 TC 7 Z9 7 U1 1 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD NOV PY 2001 VL 25 IS 6 BP 564 EP 576 PG 13 WC Psychology, Developmental SC Psychology GA 483HX UT WOS:000171630700009 ER PT J AU Colevas, AD Read, R Thornhill, J Adak, S Tishler, R Busse, P Li, Y Posner, M AF Colevas, AD Read, R Thornhill, J Adak, S Tishler, R Busse, P Li, Y Posner, M TI Hypothyroidism incidence after multimodality treatment for stage III and IV squamous cell carcinomas of the head and neck SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE hypothyroidism; thyroid; radiation; thyroid-stimulating hormone ID INDUCTION CHEMOTHERAPY; THYROID ABNORMALITIES; CANCER; FLUOROURACIL; LEUCOVORIN; CISPLATIN; RADIATION; DOCETAXEL; TRIAL AB Purpose: Treatment of head-and-neck cancer patients with surgery, radiotherapy (RT), and chemotherapy has been associated with posttherapy hypothyroidism (HT). We evaluated the rate of posttherapy HT in patients with locally advanced squamous cell carcinoma of the head and neck, treated with multimodality therapy to determine which factors might predict this condition and at what interval the condition developed. Methods: We reviewed the prospectively collected thyroid function data of patients treated with sequential chemotherapy, RT, and neck dissection. The incidence of posttherapy HT was estimated. The patients tumor, and treatment factors possibly associated with HT were evaluated. Results: Of 203 patients, 118 had data adequate for evaluation. HT developed in 45% at a median of 24.4 months after therapy. HT occurred in 14% and 27% of patients at 6 months and 1 year after treatment, respectively. Univariate and multivariate analyses of sex, age, RT dose, RT fractionation, T and N stage, tumor site, and neck dissection failed to identify a clinically relevant risk factor. Conclusions: A high number of patients undergoing aggressive organ-sparing multimodality therapy for advanced squamous cell carcinoma of the head and neck are at risk for subsequent HT. We recommend that all patients definitively irradiated to the head and neck region undergo frequent serum thyroid-stimulating hormone screening for HT, beginning 6 months after RT. (C) 2001 Elsevier Science Inc. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Colevas, AD (reprint author), NCI, Canc Therapy Evaluat Program, DCTD, Invest Drug Branch, Execut Plaza N,Room 7131,6130 Execut Blvd, Rockville, MD 20852 USA. OI Thornhill, John/0000-0002-2923-0059 NR 17 TC 44 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2001 VL 51 IS 3 BP 599 EP 604 DI 10.1016/S0360-3016(01)01688-1 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 487TX UT WOS:000171892800004 PM 11597798 ER PT J AU Shill, HA Hallett, M AF Shill, HA Hallett, M TI Cerebellar diseases SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID MULTIPLE SYSTEM ATROPHY; FRIEDREICHS ATAXIA; ABNORMALITIES; DEGENERATION AB Cerebellar diseases are recognized by a combination of clinical findings consisting of gait ataxia, dysarthria, incoordination and eye movement abnormalities. The patient with a cerebellar syndrome can be classified by age of onset of symptoms and course of illness. In general, an acute presentation is more likely to have a symptomatic cause whereas a chronic, progressive course is likely to represent a neurodegenerative condition. Increasingly, the spectrum of cerebellar degeneration is being elucidated as molecular techniques identify genetic causes. This review synthesizes the clinical features of cerebellar dysfunction and presents a method for classifying the cerebellar disorders. Evaluation would then follow according to this classification and prognosis and treatment based on specific etiology determined. C1 NINCDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINCDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Rm 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 34 TC 2 Z9 2 U1 0 U2 0 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD NOV PY 2001 VL 13 IS 4 BP 261 EP 267 PG 7 WC Psychiatry SC Psychiatry GA 490UR UT WOS:000172071000004 ER PT J AU Brady, JP Garland, DL Green, DE Tamm, ER Giblin, FJ Wawrousek, EF AF Brady, JP Garland, DL Green, DE Tamm, ER Giblin, FJ Wawrousek, EF TI alpha B-crystallin in lens development and muscle integrity: A gene knockout approach SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HEAT-SHOCK-PROTEIN; DESMIN-RELATED MYOPATHY; NON-LENTICULAR TISSUES; OXYGEN IN-VIVO; A-CRYSTALLIN; HYPERBARIC-OXYGEN; SKELETAL-MUSCLE; NONLENTICULAR TISSUES; MOLECULAR CHAPERONE; MISSENSE MUTATION AB Purpose. To study the role of alphaB-crystallin (alphaB) in the developing lens and its importance in lens structure and function. Methods. Gene targeting in embryonic stem cells was used to generate mouse lines in which the alphaB gene and its protein product were absent. Gene structure and expression were characterized by genomic Southern blot, immunoblot, and Northern blot analyses, and two-dimensional gel electrophoresis. The gene knockout mice were screened for cataract with slit lamp biomicroscopy, and dissected tenses were examined with dark field microscopy. Lenses and other tissues were analyzed by standard histology and immunohistochemistry. Chaperone activity was determined by heating lens homogenate supernatants anti measuring absorbance changes. Results. In an unexpected result, lenses in the alphaB gene knockout mice developed normally and were remarkably similar to wild-type mouse lenses. All the other crystallins were present. The thermal stability of a lens homogenate supernatant was mildly compromised, and when oxidatively stressed in vivo with hyperbaric oxygen, the knockout lenses reacted similarly to wild type. In targeting the alphaB gene. the adjacent HSPB2 gene. which is not expressed in the lens, was also disrupted. Loss of alphaB and/or HSPB2 function leads to degeneration of some skeletal Muscles. Conclusions. alphaB is not essential for normal development of a transparent lens in the mouse. and therefore is more dispensable to the lens than the closely related alphaA-crystallin. It may play a small role in maintaining transparency throughout life. alphaB and/or the closely related HSPB2 is required to maintain muscle cell integrity in some skeletal muscles. C1 NEI, NIH, Bethesda, MD 20892 USA. NIH, Pathol Sect, Off Res Serv, Bethesda, MD 20892 USA. Univ Erlangen Nurnberg, Dept Anat, D-8520 Erlangen, Germany. Oakland Univ, Eye Res Inst, Rochester, MI USA. RP Wawrousek, EF (reprint author), NEI, NIH, Bldg 6,Room 218,6 Ctr Dr MSC 2730, Bethesda, MD 20892 USA. RI Wawrousek, Eric/A-4547-2008 FU NEI NIH HHS [EY05230, EY02027] NR 58 TC 201 Z9 209 U1 0 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2001 VL 42 IS 12 BP 2924 EP 2934 PG 11 WC Ophthalmology SC Ophthalmology GA 488ZK UT WOS:000171967100029 PM 11687538 ER PT J AU Katz, ML Redmond, TM AF Katz, ML Redmond, TM TI Effect of Rpe65 knockout on accumulation of lipofuscin fluorophores in the retinal pigment epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID AGE-RELATED-CHANGES; DIETARY VITAMIN-A; MACULAR DEGENERATION; FLUORESCENCE; DYSTROPHY; ABCR; RAT; PROTEIN; DISEASE; DAMAGE AB Purpose. In all mammalian species examined to date the retinal pigment epithelium (RPE) has been found to accumulate autofluorescent lysosomal storage bodies (lipofuscin) during senescence. Substantial evidence indicates that retinoids in the RPE-retina complex play a major role in RPE lipofuscin formation. Indeed, at least one RPE lipofuscin fluorophore is derived in part from vitamin A aldehyde. However, the precise mechanisms by which retinoids modulate RPE lipofuscin accumulation have not been elucidated. In mice without a functional Rpe65 gene, isomerization of all-trans- to 11-cis-retinol is blocked. Experiments were performed to determine whether this impairment of retinoid metabolism alters RPE lipofuscin accumulation. Methods. RPE lipofuscin fluorophore content was compared in 12- to 13-month-old Rpe65(+/+), Roe65(+/-), and Rpe65(-/-) mice. Lipofuscin fluorophore content was determined using quantitative fluorometric measurements. RPE lipofuscin content was also estimated with quantitative Ultrastructural techniques. Results. In the Rpe65(-/-) mice, RPE lipofuscin fluorophore accumulation was almost abolished. In addition, a significantly reduced accumulation of lipofuscin fluorophores was also observed in the RPe65(+/-) animals. The inability of the RPE of Rpe65(-/-) mice to supply 11-cis-retinal from the RPE to the retinal photoreceptors was accompanied by a massive accumulation of lipid droplets in the RPE that appeared to contain substantial amounts of retinoids. Conclusions. These findings indicate that formation of RPE lipofuscin fluorophores is almost completely dependent on a normal visual cycle. The absence of retinal (both all-trans and 11-cis) in Rpe65 knockout mice drastically reduced formation of lipofuscin fluorophores in these animals. Even an excessive accumulation of retinyl fatty acid esters in the RPE of Rpe65 knockout mice did not contribute to lipofuscin accumulation. C1 Univ Missouri, Sch Med, Mason Eye Inst, Columbia, MO 65212 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Katz, ML (reprint author), Univ Missouri, Sch Med, Mason Eye Inst, 1 Hosp Dr, Columbia, MO 65212 USA. OI Redmond, T. Michael/0000-0002-1813-5291 NR 46 TC 82 Z9 84 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2001 VL 42 IS 12 BP 3023 EP 3030 PG 8 WC Ophthalmology SC Ophthalmology GA 488ZK UT WOS:000171967100042 PM 11687551 ER PT J AU Fletcher, BW Grella, CE AF Fletcher, BW Grella, CE TI Preface to the JAR special issue: The Drug Abuse Treatment Outcome Studies for Adolescents SO JOURNAL OF ADOLESCENT RESEARCH LA English DT Editorial Material ID ANTISOCIAL PERSONALITY-DISORDER; SUBSTANCE USE DISORDERS; HIV RISK BEHAVIORS; HOMELESS ADOLESCENTS; CONDUCT DISORDER; COMORBIDITY; RUNAWAY; SEX C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Drug Abuse Res Ctr, Los Angeles, CA 90024 USA. RP Fletcher, BW (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Rm 5159,MSC 9589, Bethesda, MD 20892 USA. NR 27 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0743-5584 J9 J ADOLESCENT RES JI J. Adolesc. Res. PD NOV PY 2001 VL 16 IS 6 BP 537 EP 544 DI 10.1177/0743558401166001 PG 8 WC Psychology, Developmental SC Psychology GA 484QR UT WOS:000171701500001 ER PT J AU Delany, PJ Broome, KM Flynn, PM Fletcher, BW AF Delany, PJ Broome, KM Flynn, PM Fletcher, BW TI Treatment service patterns and organizational structures: An analysis of programs in DATOS-A SO JOURNAL OF ADOLESCENT RESEARCH LA English DT Article ID DRUG-ABUSE TREATMENT; JUVENILE JUSTICE SYSTEM; FOLLOW-UP OUTCOMES; TREATMENT RETENTION; TREATMENT UNITS; SUBSTANCE USE; EPIDEMIOLOGY; DISORDERS; YOUTH AB The availability of a variety of treatment services was examined within a national sample of programs treating adolescent drug abuse patients. Treatment service delivery profiles were created and examined in the context of organizational variables such as program modality program directors' academic credentials, program capacity staff composition, accreditation, and patient problems. Results suggested that distinct profiles of services existed within residential and outpatient modalities and that these service profiles were related both to organizational factors and to patient problem profiles. C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. Texas Christian Univ, Ft Worth, TX 76129 USA. RP Delany, PJ (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd, Bethesda, MD 20892 USA. NR 41 TC 16 Z9 16 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0743-5584 J9 J ADOLESCENT RES JI J. Adolesc. Res. PD NOV PY 2001 VL 16 IS 6 BP 590 EP 607 DI 10.1177/0743558401166004 PG 18 WC Psychology, Developmental SC Psychology GA 484QR UT WOS:000171701500004 ER PT J AU Whetstone, LM Fozard, JL Metter, EJ Hiscock, BS Burke, R Gittings, N Fried, LP AF Whetstone, LM Fozard, JL Metter, EJ Hiscock, BS Burke, R Gittings, N Fried, LP TI The Physical Functioning Inventory: A procedure for assessing physical function in adults SO JOURNAL OF AGING AND HEALTH LA English DT Article ID MEDICAL CONDITIONS; OLDER ADULTS; DISABILITY; LIMITATIONS; RELIABILITY; AGREEMENT; VALIDITY; CARE AB The Physical Functioning Inventory, an instrument designed to assess changes in how and how often activities are performed in persons reporting difficulty with a task as well as in those who do not, is described. The measure is designed for adults. Interrater and test-retest reliability were assessed with active participants in the Baltimore Longitudinal Study of Aging (BLSA). Percentage agreement ranged from 63% to 100%. The instrument was also given to 392 inactive BLSA participants as part of a follow-up telephone interview. Fifty-eight percent of the respondents reported no difficulty in per-forming a task, yet reported a change in how or how often they performed that task. The results indicate that the instrument is reliable and effective in detecting early stages of disability in activities of daily living, instrumental activities of daily living, and mobility. The instrument is somewhat less reliable for moderate and strenuous physical activities. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, Longitudinal Studies Sect, Clin Invest Lab, Baltimore, MD 21224 USA. RP Metter, EJ (reprint author), NIA, Gerontol Res Ctr, Longitudinal Studies Sect, Clin Invest Lab, Box 6,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Fozard, James Leonard/B-3660-2009 NR 26 TC 12 Z9 12 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD NOV PY 2001 VL 13 IS 4 BP 467 EP 493 DI 10.1177/089826430101300402 PG 27 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 481WP UT WOS:000171543700002 PM 11813737 ER PT J AU Young, Y Myers, AH Provenzano, G AF Young, Y Myers, AH Provenzano, G TI Factors associated with time to first hip fracture SO JOURNAL OF AGING AND HEALTH LA English DT Article ID RISK-FACTORS; OLDER ADULTS; WOMEN; FALLS; OSTEOPOROSIS; POPULATION; MEN AB Objective: To examine the relationship between risk factors associated with first hip fracture ever and its time to first fracture. Methods: Data were from the Longitudinal Study on Aging. Of the 7,527 participants, 334 sustained a first hip fracture between 1984 and 1991. Results: Results from the Cox proportional hazards model indicate the time to first fracture was inversely related to the number of risk factors involved. The risk factors significantly associated with first fracture were increasing age, female, Caucasian race, history of falls, insufficient exercise, infrequent church attendance (a likely proxy for outside the home activities), hospitalization in the year before the study, and low body mass index. Conclusion: As the number of risk factors increases, the estimated time to fracture becomes shorter; thus. the window of opportunity for prevention is smaller. To reduce the incidence of first hip fracture and to prolong the time to first fracture, interventions should focus on modifiable risk factors identified: increasing exercise, increasing outside-the-home activities, and improving or maintaining body mass index. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. NIA, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Battelle Inc, Ctr Publ Hlth Res & Evaluat, Sequim, WA USA. RP Young, Y (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, 624 N Broadway, Baltimore, MD 21205 USA. EM yyoung1@jhsph.edu NR 31 TC 20 Z9 21 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 EI 1552-6887 J9 J AGING HEALTH JI J. Aging Health PD NOV PY 2001 VL 13 IS 4 BP 511 EP 526 DI 10.1177/089826430101300404 PG 16 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 481WP UT WOS:000171543700004 PM 11813738 ER PT J AU Jakob, T Ring, J Udey, MC AF Jakob, T Ring, J Udey, MC TI Multistep navigation of Langerhans/dendritic cells in and out of the skin SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Langerhans cells; dendritic cells; migration-trafficking; adhesion; chemokines; skin; allergy; immune regulation ID HUMAN PERIPHERAL-BLOOD; CPG-CONTAINING OLIGODEOXYNUCLEOTIDES; INFLAMMATORY PROTEIN 3-ALPHA; CADHERIN-MEDIATED ADHESION; CUTANEOUS DENDRITIC CELLS; NECROSIS-FACTOR-ALPHA; DRAINING LYMPH-NODES; CONTACT HYPERSENSITIVITY; CHEMOKINE RECEPTORS; TH1 RESPONSES AB Langerhans cells (LCs) are specialized antigen-presenting cells that reside in the epidermis as sentinels of the immune system. LCs constantly monitor the epidermal microenvironment by taking up antigen and processing it into fragments that can be recognized by cells of the adaptive immune response. Because of their unique migratory ability, LCs can transport antigen from the epidermis to regional lymph nodes, where they can initiate systemic immune responses. The mechanisms of LC trafficking thus seem to be of particular relevance for the induction and maintenance of cutaneous immunity. LCs or their putative precursors express surface molecules that allow them to home to skin and localize in the epidermis for prolonged periods of time. Tissue injury, microbial infection, and other perturbants of epidermal homeostasis (eg, contact allergens) provide danger signals, leading to a local production of proinflammatory cytokines that induce LC mobilization to the lymphoid tissue. At the same time, signals are generated that recruit LC precursors into the skin to maintain the epidermal LC population. Distinct pairs of chemokines and their receptors control the migration from blood to epidermis and from there to the regional lymphatics. In addition, trafficking is controlled at the level of cell adhesion, where LCs downregulate some adhesion molecules to exit the epidermis and upregulate others to migrate across the extracellular matrix and home to T-cell areas of regional lymphoid tissue. The improved understanding of mechanisms that regulate LC trafficking might offer new opportunities for therapeutic interventions to suppress, stimulate, or deviate cutaneous immune responses. C1 Tech Univ Munich, Dept Dermatol & Allergy Biederstein, Div Environm Dermatol & Allergy GSF TUM, D-80802 Munich, Germany. GSF, Natl Res Ctr Environm & Hlth, Div Environm Dermatol & Allergy GSF TUM, Neuherberg, Germany. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Jakob, T (reprint author), Tech Univ Munich, Dept Dermatol & Allergy Biederstein, Div Environm Dermatol & Allergy GSF TUM, Biedersteiner Str 29, D-80802 Munich, Germany. RI Jakob, Thilo/J-1621-2012 NR 66 TC 97 Z9 105 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2001 VL 108 IS 5 BP 688 EP 696 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 498RG UT WOS:000172523800005 PM 11692090 ER PT J AU Chapin, RE Wine, RN Harris, MW Borchers, CH Haseman, JK AF Chapin, RE Wine, RN Harris, MW Borchers, CH Haseman, JK TI Structure and control of a cell-cell adhesion complex associated with spermiation in rat seminiferous epithelium SO JOURNAL OF ANDROLOGY LA English DT Article DE cadherins; cell adhesions; control; integrins; spermiation ID INTEGRIN-LINKED KINASE; PROTEIN-KINASE; ECTOPLASMIC SPECIALIZATIONS; TYROSINE PHOSPHORYLATION; SERTOLI CELLS; CYTOPLASMIC DOMAIN; MAP KINASE; SIGNALING PROTEINS; ADHERENS JUNCTION; DOWN-REGULATION AB Spermiation, the release of late spermatids from the Sertoli cell, is disrupted by a number of toxicants. Control of the spermiation process, and the proteins that interact to adhere mature spermatids to Sertoli cells, is poorly understood. In these studies we used immunohistochemistry, coimmunoprecipitation/Western blotting, and mass spectrometry to refine an earlier model of sperm adhesion proposed by our laboratory. We have identified specific proteins linked together as part of a multiprotein complex, as well as several additional proteins (cortactin, ERK1/2, and 14-3-3 zeta) that may be functioning in both structural and signal transduction roles. The current and prior data suggest that protein phosphorylation is central to the control of spermiation. We also present and characterize an in vitro tubule culture system that allowed functional testing of the spermiation model by pharmacologic manipulation, and yielded data consistent with the importance of protein phosphorylation in spermiation. C1 NIEHS, Reprod Toxicol Grp, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Chapin, RE (reprint author), Dupont Pharmaceut Co, POB 30,1090 Elkton Rd, Newark, DE 19714 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 82 TC 66 Z9 69 U1 0 U2 1 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD NOV-DEC PY 2001 VL 22 IS 6 BP 1030 EP 1052 PG 23 WC Andrology SC Endocrinology & Metabolism GA 487FU UT WOS:000171863600015 PM 11700851 ER PT J AU Sass, HJ Musco, G Stahl, SJ Wingfield, PT Grzesiek, S AF Sass, HJ Musco, G Stahl, SJ Wingfield, PT Grzesiek, S TI An easy way to include weak alignment constraints into NMR structure calculations SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE orientation; protein; pseudo-inverse; residual tensorial coupling; structure calculation ID ORIENTED MACROMOLECULES; DIPOLAR COUPLINGS; SPECTRA AB We have recently shown that an energy penalty for the incorporation of residual tensorial constraints into molecular structure calculations can be formulated without the explicit knowledge of the Saupe orientation tensor (Moltke and Grzesiek, J. Biomol. NMR, 1999, 15, 77-82). Here we report the implementation of such an algorithm into the program X-PLOR. The new algorithm is easy to use and has good convergence properties. The algorithm is used for the structure refinement of the HIV-1 Nef protein using 252 dipolar coupling restraints. The approach is compared to the conventional penalty function with explicit knowledge of the orientation tensor's amplitude and rhombicity. No significant differences are found with respect to speed, Ramachandran core quality or coordinate precision. C1 Univ Basel, Biozentrum, Dept Biol Struct, CH-4056 Basel, Switzerland. Hosp San Raffaele, Dept Neurosci, Dept Biol & Technol Res, I-20132 Milan, Italy. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Sass, HJ (reprint author), Univ Basel, Biozentrum, Dept Biol Struct, CH-4056 Basel, Switzerland. RI musco, giovanna/I-7122-2012 OI musco, giovanna/0000-0002-0469-2994 NR 22 TC 37 Z9 37 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD NOV PY 2001 VL 21 IS 3 BP 275 EP 280 DI 10.1023/A:1012998006281 PG 6 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 496EM UT WOS:000172383300008 PM 11775744 ER PT J AU Koch, CA Chrousos, GP AF Koch, CA Chrousos, GP TI Editorial: Is the Diminuto/Dwarf1 gene involved in physiologic adrenocortical size regulation and tumor formation? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CUSHINGS-DISEASE; APOPTOSIS; ATROPHY; MANAGEMENT; NEOPLASMS; SURVIVIN C1 NINDS, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NINDS, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. EM kochc@exchange.nih.gov; chrousog@mail.nih.gov RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 27 TC 2 Z9 2 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5127 EP 5129 DI 10.1210/jc.86.11.5127 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600005 PM 11701664 ER PT J AU Phillips, SA Rotman-Pikielny, P Lazar, J Ando, S Hauser, P Skarulis, MC Brucker-Davis, F Yen, PM AF Phillips, SA Rotman-Pikielny, P Lazar, J Ando, S Hauser, P Skarulis, MC Brucker-Davis, F Yen, PM TI Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR-BETA GENE; GENERALIZED RESISTANCE; TRANSCRIPTIONAL REGULATION; BINDING DOMAIN; LIGAND-BINDING; MUTATION; FAMILIES; MICE; EXPRESSION; PHENOTYPE AB Resistance to thyroid hormone (RTH) is a syndrome in which patients have elevated thyroid hormone (TH) levels and decreased sensitivity to its action. We describe a child with extreme RTH and a severe phenotype. A 22-month-old female presented to the NIH with goiter, growth retardation, short stature, and deafness. Additionally, the patient had hypotonia, mental retardation, visual impairment, and a history of seizures. Brain magnetic resonance imaging showed evidence of demyelination and bilateral ventricular enlargement. The patient had markedly elevated free T(3) and free T(4) levels of more than 2000 pg/dl (normal, 230-420 pg/dl) and more than 64 pmol/liter (normal, 10.3-20.6 pmol/liter), respectively, and TSH of 6.88 mU/liter (normal, 0.6-6.3 mU/liter). These are the highest TH levels reported for a heterozygous RTH patient. A T(3) stimulation test confirmed the diagnosis of RTH in the pituitary and peripheral tissues. Molecular analyses of the patient's genomic DNA by PCR identified a single base deletion in exon 10 of her TR beta gene that resulted in a frameshift and early stop codon. This, in turn, encoded a truncated receptor that lacked the last 20 amino acids. Cotransfection studies showed that the mutant TR was transcriptionally inactive even in the presence of 10(-6) M T(3) and had strong dominant negative activity over the wild-type receptor. It is likely that the severely defective TR beta mutant contributed to the extreme RTH phenotype and resistance in our patient. C1 NIDDKD, Clin Endocrinol Branch, Mol Regulat & Neuroendocrinol Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Univ Nice, Ctr Hosp, Dept Med, Nice, France. RP Yen, PM (reprint author), NIDDKD, Clin Endocrinol Branch, Mol Regulat & Neuroendocrinol Sect, NIH, Bldg 10,Room 8D12, Bethesda, MD 20892 USA. EM pauly@intra.niddk.nih.gov NR 34 TC 14 Z9 16 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5142 EP 5147 DI 10.1210/jc.86.11.5142 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600008 PM 11701667 ER PT J AU Gibril, F Venzon, DJ Ojeaburu, JV Bashir, S Jensen, RT AF Gibril, F Venzon, DJ Ojeaburu, JV Bashir, S Jensen, RT TI Prospective study of the natural history of gastrinoma in patients with MEN1: Definition of an aggressive and a nonaggressive form SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; ZOLLINGER-ELLISON-SYNDROME; PROGNOSTIC FACTORS; LONG-TERM; METASTATIC GASTRINOMAS; SURGICAL-TREATMENT; PANCREATIC TUMORS; TYPE-1; MANAGEMENT; SURGERY AB The natural history of pancreatic endocrine tumors (PETS) in patients with MEN1 is largely unknown. Recent studies in patients with sporadic PETS show that in a subset, tumor growth is aggressive. To determine whether PETS in patients with MEN1 show similar growth behavior, we report results from a long-term prospective study of 57 patients with MEN1 and Zollinger-Ellison syndrome. All patients had tumor imaging studies yearly, and the mean follow-up was 8 yr. Only patients with PETS 2.5 em or larger underwent abdominal surgical exploration. Hepatic metastases occurred in 23%, and in 14% tumors demonstrated aggressive growth. Three tumor-related deaths occurred, each due to liver metastases, and in each, aggressive tumor growth was present. Overall, 4% of the study group, 23% with liver metastases and 38% with aggressive disease, died. Aggressive growth was associated with higher gastrins and larger tumors. Patients with liver metastases with aggressive growth differed from those with liver metastases without aggressive growth in age at MEN1 onset or diagnosis and primary tumor size. Survival was decreased (P = 0.0012) in patients with aggressive tumor growth compared with those with liver metastases without aggressive growth or with no liver metastases without aggressive growth. Based on these results a number of factors were identified that may be clinically useful in determining in which patients aggressive tumor growth may occur. These results demonstrate in a significant subset of patients with MEN1 and Zollinger-Ellison syndrome, aggressive tumor growth occurs and can lead to decreased survival. The identification of prognostic factors that identify this group will be important clinically in allowing more aggressive treatment options to be instituted earlier. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 64 TC 65 Z9 67 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5282 EP 5293 DI 10.1210/jc.86.11.5282 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600031 PM 11701693 ER PT J AU Sandrini, F Farmakidis, C Kirschner, LS Wu, SM Tullio-Pelet, A Lyonnet, S Metzger, DL Bourdony, CJ Tiosano, D Chan, WY Stratakis, CA AF Sandrini, F Farmakidis, C Kirschner, LS Wu, SM Tullio-Pelet, A Lyonnet, S Metzger, DL Bourdony, CJ Tiosano, D Chan, WY Stratakis, CA TI Spectrum of mutations of the AAAS gene in Allgrove syndrome: Lack of mutations in six kindreds with isolated resistance to corticotropin SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SODIUM-CHANNEL GENE; TRIPLE-A SYNDROME; GLUCOCORTICOID DEFICIENCY; ACHALASIA; ALACRIMA; DISEASE; INSENSITIVITY; INSUFFICIENCY; RECEPTOR; MARKERS AB Familial glucocorticoid deficiency due to corticotropin (ACTH) resistance consists of two distinct genetic syndromes that are both inherited as autosomal recessive traits: isolated ACTH resistance (iACTHR), which may be caused by inactivating mutations of the ACTH receptor (the MC2R gene) or mutations in an as yet unknown gene(s), and Allgrove syndrome (AS). The latter is also known as triple-A syndrome (MIM 231550). In three large cohorts of AS kindreds, the disease has been mapped to chromosome 12; most recently, mutations in the AAAS gene on 12q13 were found in these AS families. AAAS codes for the WD-repeat containing ALADIN (for alacrima-achalasia-adrenal insufficiency-neurologic disorder) protein. We investigated families with iACTHR (n = 4) and AS (n = 6) and a Bedouin family with ACTHR and a known defect of the TSH receptor. Four AS families were, of mixed extraction from Puerto Rico (PR); most of the remaining six families were Caucasian families from North America, (NA). Sequencing analysis found no MC2R genetic defects in any of the kindreds. No iACTHR kindreds, but all of AS families, had AAAS mutations. The previously reported 1VS14+1G -->A splice donor mutation was found in all PR families, apparently due to a founder effect; one NA kindred was heterozygous for this mutation. In the latter family, long-range PCR failed to identify a deletion or other rearrangements of the AAAS gene. No other heterozygote or transmitting parent had any phenotype that could be considered part, off AS. The IVS14+1G -->A mutation results in a premature termination of the predicted protein; although it was present in all PR families (in the homozygote state in three of them), there was substantial clinical variation between them. One PR family also carried a novel splice donor mutation of the AAAS gene in exon 11, IVS11+1G -->A; the proband was a compound heterozygote. A novel point mutation, 43C -->A(Gln(16)Lys), in exon 1 of the AAAS gene was identified in the homozygote state in a Canadian AS kindred with a milder AS phenotype. The predicted amino acid substitution in this family is located in a sequence that may participate in the preservation of stability of ALADIN beta -strands, whereas the splicing mutation in exon 11 may interfere with the formation of WD repeats in this molecule. We conclude that 1) AAAS does not appear to be frequently mutated in families with iACTHR; 2) AAAS is mutated in AS families from PR (that had previously been mapped to 12q13) and NA; and, 3) there is significant clinical variability between patients with the same HAAS defect. C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Dept Cell Biol, Washington, DC 20007 USA. Georgetown Univ, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Hop Necker Enfants Malad, Dept Genet, U393, INSERM,Unite Rech Handicaps Genet, F-75743 Paris 15, France. British Columbia Childrens Hosp, Endocrinol & Diabet Unit, Vancouver, BC V6H 3V4, Canada. Childrens Hosp, Dept Pediat, San Juan, PR 00907 USA. Rambam Med Ctr, Dept Pediat, IL-31096 Haifa, Israel. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. EM stratakc@ccl.nichd.nih.gov NR 25 TC 52 Z9 56 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5433 EP 5437 DI 10.1210/jc.86.11.5433 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600053 PM 11701718 ER PT J AU Mather, KJ Hunt, AE Steinberg, HO Paradisi, G Hook, G Katz, A Quon, MJ Baron, AD AF Mather, KJ Hunt, AE Steinberg, HO Paradisi, G Hook, G Katz, A Quon, MJ Baron, AD TI Repeatability characteristics of simple indices of insulin resistance: Implications for research applications SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; GLUCOSE-TOLERANCE; CELL FUNCTION; SENSITIVITY; TESTS; INVIVO; INDEX; SECRETION; DISPOSAL; BRUNECK AB The objectives of this study were to evaluate test characteristics, such as normality of distribution, variation, and repeatability, of simple fasting measures of insulin sensitivity and to use the results to choose among these measures. Duplicate fasting samples of insulin and glucose were collected before 4 h of euglycemic hyperinsulinemic clamping using insulin infusion rates ranging from 40-600 mU/m(2.)min. Currently recommended estimates of insulin sensitivity, including the fasting insulin, 40/insulin, the homeostasis model assessment, the logarithmic transformation of the homeostasis model assessment, and the Quantitative Insulin Sensitivity Check Index, were evaluated. The normality of distribution and the variability of the tests (coefficient of variation and discriminant ratio) were compared between the measures and against the "gold standard" hyperinsulinemic clamp. Data from 253 clamp studies in 152 subjects were examined, including 79 repeated studies for repeatability analysis. In subjects ranging from lean to diabetic, the log transformed fasting measures combining insulin and glucose had normal distributions and test characteristics superior to the stasis model assessment coefficient of variation, 0.55; discriminant ratio, 13; Quantitative Insulin Sensitivity Check Index coefficient of variation, 0.05; discriminant ratio, 10) and statistically comparable to euglycemic hyperinsulinemic clamps (coefficient of variation, 0.10; discriminant ratio, 6.4). These favorable characteristics helped explain the superior correlations of these measures with the hyperinsulinemic clamps among insulin-resistant subjects. Furthermore, therapeutic changes in insulin sensitivity were as readily demonstrated with these simple measures as with the hyperinsulinemic clamp. The test characteristics of the logarithmic transformation of the homeostasis model assessment and the Quantitative Insulin Sensitivity Check Index are superior to other simple indices of insulin sensitivity. This helps explain their excellent correlations with formal measures both at baseline and with changes in insulin sensitivity and supports their broader application in clinical research. C1 Indiana Univ, Sch Med, Div Endocrinol & Metab, Indianapolis, IN 46250 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Mather, KJ (reprint author), Indiana Univ, Sch Med, Div Endocrinol, CL 459,541 N Clin Dr, Indianapolis, IN 46202 USA. EM kmather@iupui.edu RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU NCRR NIH HHS [MO1-RR750-19]; NIDDK NIH HHS [DK20452, DK42469] NR 26 TC 236 Z9 259 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5457 EP 5464 DI 10.1210/jc.86.11.5457 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600057 PM 11701722 ER PT J AU Ando, S Sarlis, NJ Oldfield, EH Yen, PM AF Ando, S Sarlis, NJ Oldfield, EH Yen, PM TI Somatic mutation of TR beta can cause a defect in negative regulation of TSH in a TSH-secreting pituitary tumor SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID THYROID-HORMONE RECEPTOR; INSTITUTES-OF-HEALTH; RESISTANCE; GENE; KINDREDS; MUTANT; IDENTIFICATION; TRANSCRIPTION; MICROADENOMA; EXPRESSION AB In patients with TSH-secreting tumors (TSHomas), serum TSH is poorly suppressed by thyroid hormone. The mechanism for this defect in negative regulation of TSH secretion is not known. To investigate the possibility of a somatic mutation of TR causing this defect, we performed mutational analysis of TR beta by RT-PCR using RNA obtained from five surgically resected TSHomas. In one TSHoma, we identified a somatic mutation in the ligand-binding domain of TR beta that caused a His to Tyr substitution at codon 435 of TR beta1 corresponding to codon 450 of TR beta2. Interestingly, this mutation occurred in the same codon as two mutations (TR beta H435L and H435Q) previously identified in patients with the syndrome of resistance to thyroid hormone. This mutant TR beta had impaired T(3) binding and T(3)-mediated negative regulation. It also blocked the negative regulation by wild-type TR beta2 on glycoprotein hormone a-subunit and TSH beta reporter genes in cotransfection studies. Our results demonstrate that somatic mutation of TR beta occurred in a TSHoma and was probably responsible for the defect in negative regulation of TSH by thyroid hormone in the tumor. C1 NIDDKD, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Yen, PM (reprint author), NIDDKD, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bldg 10,Room 8D12, Bethesda, MD 20892 USA. EM pauly@intra.niddk.nih.gov NR 30 TC 63 Z9 66 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5572 EP 5576 DI 10.1210/jc.86.11.5572 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600072 PM 11701737 ER PT J AU Kino, T Stauber, RH Resau, JH Pavlakis, GN Chrousos, GP AF Kino, T Stauber, RH Resau, JH Pavlakis, GN Chrousos, GP TI Pathologic human GR mutant has a transdominant negative effect on the wild-type GR by inhibiting its translocation into the nucleus: Importance of the ligand-binding domain for intracellular GR trafficking SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN GLUCOCORTICOID RECEPTOR; PRIMARY CORTISOL RESISTANCE; ACID-BINDING; PROTEIN; LOCALIZATION; MUTATION; DETERMINANTS; TRANSPORT; EXPORTIN; COMPLEX AB The syndrome of familial or sporadic glucocorticoid resistance is characterized by hypercortisolism without the clinical stigmata of Cushing syndrome. This condition is usually caused by mutations of the human GR, a ligand-activated transcription factor that shuttles between the cytoplasm and the nucleus. A pathological human mutant receptor, in which Ile was replaced by Asn at position 559, had negligible ligand binding, was transcriptionally extremely weak, and exerted a transdominant negative effect on the transactivational activity of the wild-type GR, causing severe glucocorticoid resistance in the heterozygous state. To understand the mechanism of this mutant's trans-dominance, we constructed several N-terminal GR fusion chimeras to green fluorescent protein (GFP) and demonstrated that their transactivational activities were similar to those of the original proteins. The GFP-human (h) GR alpha I559N chimera was predominantly localized in the cytoplasm, and only high doses or prolonged glucocorticoid treatment triggered complete nuclear import that took 180 vs. 12 min for GFP-hGR alpha. Furthermore, hGR alpha I559N inhibited nuclear import of the wild-type GFP-hGR alpha, suggesting that its trans-dominant activity on the wild-type receptor is probably exerted at the process of nuclear translocation. As the ligand-binding domain (LBD) of the GR appears to play an important role in its nucleocytoplasmic shuttling, we also examined two additional GR-related fusion proteins. The natural hGRisoform beta (GFP-hGR beta), containing a unique LBD, was transactivation-inactive, moderately trans-dominant, and localized instantaneously and predominantly in the nucleus; glucocorticoid addition did not change its localization. Similarly, GFP-hGR514, lacking the entire LBD, was instantaneously and predominantly localized in the nucleus regardless of presence of glucocorticoids. Using a cell fusion system we demonstrated that nuclear export of GFP-hGR alpha I559N (250 min) and GFP-hGR beta (300 min) was drastically impaired compared with that of GFP-hGR alpha (50 min) and GFP-hGR514 (50 min), suggesting that an altered LBD may impede the exit of the GR from the nucleus. We conclude that the trans-dominant negative effect of the pathological mutant is exerted primarily at the translocation step, whereas that of the natural isoform beta is exerted at the level of transcription. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Human Retrovirus Sect, Ctr Canc Res, Frederick, MD 21702 USA. RP Kino, T (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42,10 Ctr Dr,MSC 1583, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov; james.resau@vai.org OI Stauber, Roland/0000-0002-1341-4523 NR 36 TC 72 Z9 79 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5600 EP 5608 DI 10.1210/jc.86.11.5600 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600076 PM 11701741 ER PT J AU Cohen-Mansfield, J Pawlson, G Lipson, S Volpato, S AF Cohen-Mansfield, J Pawlson, G Lipson, S Volpato, S TI The measurement of health: A comparison of indices of disease severity SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE adult day care; aged; severity-of-illness index ID ILLNESS RATING-SCALE; VALIDATION AB This study compared the utility of different health indicators in frail older people, as a component of a larger study of medical evaluations of 183 adult day care participants in five Maryland centers. Indices examined included: number of disease categories, number of active categories, number of severe categories, number of categories with worsening trajectory, and average severity score. In predicting survival, none of the medical indicators without dementia was a strong predictor of survival. When dementia was included. number of categories with worsening trajectory seemed to be the best indicator of survival, with average severity score being a close second. Among the diagnoses, dementia and its severity were the strongest predictors of survival. Prediction of continuous stay in the community (in contrast to death or entry into a nursing home) was significant for most indices and is easier to predict from medical indices than death. Different indicators provided best utility depending on the criterion applied. (C) 2001 Elsevier science Inc. All rights reserved. C1 Hebrew Home Greater Washington, Res Inst, Rockville, MD 20852 USA. George Washington Univ, Sch Publ Hlth, Washington, DC USA. Natl Ctr Qual Assurance, Washington, DC USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Cohen-Mansfield, J (reprint author), Hebrew Home Greater Washington, Res Inst, 6111 Montrose Rd, Rockville, MD 20852 USA. RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [R01 AG08675, KO1 AG00547] NR 19 TC 2 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD NOV PY 2001 VL 54 IS 11 BP 1094 EP 1102 DI 10.1016/S0895-4356(01)00389-4 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 484PE UT WOS:000171698100004 PM 11675160 ER PT J AU Yang, YF Tomura, M Iwasaki, M Ono, S Zou, JP Uno, K Shearer, GM Fujiwara, H Hamaoka, T AF Yang, YF Tomura, M Iwasaki, M Ono, S Zou, JP Uno, K Shearer, GM Fujiwara, H Hamaoka, T TI IFN-alpha acts on T-cell receptor-triggered human peripheral leukocytes to up-regulate CCR5 expression on CD4(+) and CD8(+) T cells SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE IFN-alpha; IL-12; chemokine receptor; CCR5; T cell ID INTERFERON-GAMMA PRODUCTION; NATURAL-KILLER; CHEMOKINE RECEPTORS; STIMULATORY FACTOR; CHEMOTACTIC RESPONSIVENESS; CYTOKINE RESPONSES; IL-12 PRODUCTION; INTERLEUKIN-12; LYMPHOCYTES; STAT4 AB Interleukin-12 (IL-12) as well as IL-2 was recently shown to up-regulate CCR5 expression on T-cell receptor (TCR)triggered human T cells. Because of the functional similarity between interferon-alpha (IFN-alpha) and IL-12. the present study investigated whether IFN-alpha also up-regulates T cell CCR5 expression. CCR5 was marginally detected on T cells from unstimulated human peripheral blood leukocytes (PBLs) and only slightly induced on PBL T cells following stimulation with anti-CD3 plus anti-CD28 monoclonal antibodies (mAbs). When anti-CD3/anti-CD28-triggered PBLs were exposed to IFN-alpha. T cells expressed high levels of CCR5. The levels of CCR5 expression were comparable to those induced by IL-12. However, when purified T cells instead of unfractionated PBL were stimulated with anti-CD3/CD28 and then exposed to IL-12 or IFN-alpha. CCR5 expression was induced by IL-12 but not by IFN-alpha. IFN-alpha was found to act on anti-CD3/anti-CD28-stimulated PBL to promote their IL-12 production. Moreover, addition of anti-IL-12 mAb to IFN-alpha-stimulated cultures of anti-CD3/CD28-pretreated PBL resulted in considerable inhibition of CCR5 expression. Together, these results indicate that IFN-alpha as well as IL-12 up-regulates CCR5 expression on TCR-triggered T cells and that IFN-alpha functions not by acting directly on T cells but via enhancing IL-12 production by PBL. C1 Osaka Univ, Grad Sch Med, Dept Oncol C6, Biomed Res Ctr, Suita, Osaka 5650871, Japan. Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China. Louis Pasteur Ctr Med Res, Kyoto 606, Japan. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Fujiwara, H (reprint author), Osaka Univ, Grad Sch Med, Dept Oncol C6, Biomed Res Ctr, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. NR 46 TC 19 Z9 20 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 2001 VL 21 IS 6 BP 402 EP 409 DI 10.1023/A:1013173610032 PG 8 WC Immunology SC Immunology GA 512HA UT WOS:000173317900004 PM 11811785 ER PT J AU Notkins, AL Lernmark, A AF Notkins, AL Lernmark, A TI Autoimmune type 1 diabetes: resolved and unresolved issues SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; ISLET-CELL-ANTIBODIES; PROTEIN-TYROSINE-PHOSPHATASE; HL-A ANTIGENS; INSULIN AUTOANTIBODIES; TRANSMEMBRANE PROTEIN; GENERAL-POPULATION; YOUNG-ADULTS; MELLITUS; IDDM C1 Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Robert H Williams Lab, Seattle, WA 98195 USA. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Room 121,30 Convent Dr,MSC 4322, Bethesda, MD 20892 USA. NR 45 TC 172 Z9 177 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2001 VL 108 IS 9 BP 1247 EP 1252 DI 10.1172/JCI14257 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 490KM UT WOS:000172051100002 PM 11696564 ER PT J AU Leslie, D Lipsky, P Notkins, AL AF Leslie, D Lipsky, P Notkins, AL TI Autoantibodies as predictors of disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; STEROID 21-HYDROXYLASE AUTOANTIBODIES; GLUTAMIC-ACID DECARBOXYLASE; CLINICAL ADDISONS-DISEASE; PRIMARY BILIARY-CIRRHOSIS; FIRST-DEGREE RELATIVES; CELIAC-DISEASE; RHEUMATOID-ARTHRITIS; TISSUE TRANSGLUTAMINASE; PERNICIOUS-ANEMIA C1 St Bartholomews Hosp, Dept Diabet & Metab, London EC1A 7BE, England. NIAMSD, Lab Autoimmun, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Leslie, D (reprint author), St Bartholomews Hosp, Dept Diabet & Metab, London EC1A 7BE, England. NR 46 TC 92 Z9 98 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2001 VL 108 IS 10 BP 1417 EP 1422 DI 10.1172/JCI14452 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 495QW UT WOS:000172352700002 PM 11714731 ER PT J AU Barry-Lane, PA Patterson, C van der Merwe, M Hu, ZY Holland, SM Yeh, ETH Runge, MS AF Barry-Lane, PA Patterson, C van der Merwe, M Hu, ZY Holland, SM Yeh, ETH Runge, MS TI p47phox is required for atherosclerotic lesion progression in ApoE(-/-) mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VASCULAR SMOOTH-MUSCLE; SUPEROXIDE ANION PRODUCTION; ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; NADPH-OXIDASE; PHORBOL ESTER; CELLS; EXPRESSION; ACTIVATION; P47(PHOX) AB NADPH oxidase is upregulated in smooth muscle cells (SMCs) in response to growth factor stimulation, concomitant with increased reactive oxygen species (ROS) production. We investigated the role of ROS production by NADPH oxidase in SMC responses to growth factors and in atherosclerotic lesion formation in ApoE(-/-) mice. SMCs from wild-type, p47phox(-/-), and gp91phox(-/-) mice differed markedly with respect to growth factor responsiveness and ROS generation. p47phox(-/-) SMCs had diminished superoxide production and a decreased proliferative response to growth factors compared with wild-type cells, whereas the response of gp91phox(-/-) SMCs was indistinguishable from that of wild-type SMCs. The relevance of these in vitro observations was tested by measuring atherosclerotic lesion formation in genetically modified (wild-type, p47phox(-/-), ApoE(-/-), and ApoE(-/-)/p47phox(-/-)) mice. ApoE(-/-)/p47phox(-/-) mice had less total lesion area than ApoE(-/-) mice, regardless of whether mice were fed standard chow or a high-fat diet. Together, these studies provide convincing support for the hypothesis that superoxide generation in general, and NADPH oxidase in particular, have a requisite role in atherosclerotic lesion formation, and they provide a rationale for further studies to dissect the contributions of ROS to vascular lesion formation. C1 Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ Texas, Med Branch, Sealy Ctr Mol Cardiol, Galveston, TX 77550 USA. Univ N Carolina, Carolina Cardiovasc Biol Ctr, Div Cardiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Res Ctr Cardiovasc Dis, Houston, TX USA. RP Runge, MS (reprint author), Univ N Carolina, Dept Med, 3033 Old Clin Bldg,Campus Box 7005, Chapel Hill, NC 27599 USA. FU NHLBI NIH HHS [R01 HL057352, HL-59652, HL-57352] NR 46 TC 329 Z9 338 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2001 VL 108 IS 10 BP 1513 EP 1522 DI 10.1172/JCI11927 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 495QW UT WOS:000172352700014 PM 11714743 ER PT J AU Zhang, ZS Torii, N Hu, ZY Jacob, J Liang, TJ AF Zhang, ZS Torii, N Hu, ZY Jacob, J Liang, TJ TI X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID B-VIRUS; PROTEASOME COMPLEX; GENE-PRODUCT; HBX PROTEIN; DNA-BINDING; TRANSCRIPTION FACTORS; FULMINANT-HEPATITIS; III-PROMOTERS; TRANSACTIVATION; INFECTION AB The X protein (HBX) of the hepatitis B virus (HBV) has been shown to be important for the establishment of HBV infection in vivo. Our previous studies suggested that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. In this study, we generated a series of woodchuck hepatitis virus (WHV) X mutants, including mutants of the domain interacting with the proteasome, and studied their infectivity in woodchucks. Many of the mutants were defective in transactivation but none of them were completely replication defective in vitro. In vivo, all the wild-type and some X mutant-transfected animals demonstrated evidence of infection with and-WHc and/or anti-WHs seroconversion. Most of the wild-type- and X mutant-transfected animals had transient viremia. Some animals were later challenged with infectious WHV. Animals inoculated with X mutants, including those with no serologic evidence of infection, were protected from the challenge, suggesting previous infection with resulting protective immunity. Our study demonstrates that the previously described functional domains of HBX are biologically important and the X-defective mutants, possibly as attenuated viruses, are not completely replication defective in vivo. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Cornell Univ, Coll Vet Med, Ithaca, NY 14853 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. FU NIAID NIH HHS [N01AI05399] NR 35 TC 45 Z9 46 U1 2 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2001 VL 108 IS 10 BP 1523 EP 1531 DI 10.1172/JCI13787 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 495QW UT WOS:000172352700015 PM 11714744 ER PT J AU Franklin, CL Gorelick, PL Riley, LK Dewhirst, FE Livingston, RS Ward, JM Beckwith, CS Fox, JG AF Franklin, CL Gorelick, PL Riley, LK Dewhirst, FE Livingston, RS Ward, JM Beckwith, CS Fox, JG TI Helicobacter typhlonius sp nov., a novel murine urease-negative Helicobacter species SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; CHRONIC ACTIVE HEPATITIS; SCID MICE; SYRIAN-HAMSTERS; CAMPYLOBACTER-CINAEDI; BACTERIAL-INFECTION; LABORATORY MICE; BILIS; IDENTIFICATION; GASTRITIS AB Over the past decade, several Helicobacter species have been isolated from rodents. With the advent of PCR for the diagnosis of infectious agents, it has become clear that several previously uncharacterized Helicobacter species also colonize rodents. In this report, we describe a novel urease-negative helicobacter, Helicobacter typhlonius sp. nov., which was isolated from colonies of laboratory mice independently by two laboratories. Infection of immunodeficient mice by this bacterium resulted in typhlocolitis similar to that observed with other helicobacter infections. H. typhlonius is genetically most closely related to H. hepaticus. Like H. hepaticus, it is a spiral bacterium with bipolar sheathed flagella. However, this novel species contains a large intervening sequence in its 16S rRNA gene and is biochemically distinct from H. hepaticus. Notably, H. typhlonius does not produce urease or H2S nor does it hydrolize indoxyl-acetate. Compared to other Helicobacter species that commonly colonize rodents, H. typhlonius was found to be less prevalent than H. hepaticus and H. rodentium but as prevalent as H. bilis. H. typhlonius joins a growing list of helicobacters that colonize mice and are capable of inducing enteric disease in various strains of immunodeficient mice. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Univ Missouri, Dept Vet Pathobiol, Res Anim Diagnost & Investigat Lab, Columbia, MO 65211 USA. NCI, Anim Hlth Diagnost Lab, Lab Anim Sci Program, FCRDC,Sci Applicat Int Corp, Frederick, MD 21701 USA. Forsyth Inst, Boston, MA 02115 USA. Natl Canc Inst, Vet & Tumor Pathol Sect, Ctr Canc Res, Boston, MA 02115 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, Bldg 16-825C,77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NCI NIH HHS [R01 CA067529, R01CA67529]; NCRR NIH HHS [P41RR0600] NR 48 TC 40 Z9 41 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2001 VL 39 IS 11 BP 3920 EP 3926 DI 10.1128/JCM.39.11.3920-3926.2001 PG 7 WC Microbiology SC Microbiology GA 488KK UT WOS:000171934200017 PM 11682508 ER PT J AU Muellbacher, W Boroojerdi, B Ziemann, U Hallett, M AF Muellbacher, W Boroojerdi, B Ziemann, U Hallett, M TI Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE tongue; motor cortex; bilateral motor representations; humans; TMS ID TRANSCRANIAL MAGNETIC STIMULATION; CORTICO-HYPOGLOSSAL PROJECTIONS; HUMAN BRAIN-STEM; INTRACORTICAL INHIBITION; HEMISPHERIC STROKE; EVOKED-POTENTIALS; MUSCLES; RESPONSES; LESIONS; PRIMATE AB How the human brain controls activation of the ipsilateral part of midline muscles is unknown. We studied corticospinal and corticocortical network excitability of both ipsilateral and contralateral motor representations of the tongue to determine whether they are under analogous or disparate inhibitory and facilitatory corticocortical control. Motor evoked potentials (MEPs) to unilateral focal transcranial magnetic stimulation (TMS) of the tongue primary motor cortex were recorded simultaneously from the ipsilateral and contralateral lingual muscles. Single-pulse TMS Was used to assess motor threshold (MT) and MEP recruitment. Paired-pulse TMS was used to study intracortical inhibition (ICI) and intracortical facilitation (ICF) at various interstimulus intenals (ISIs) between the conditioning stimulus (CS) and the test stimulus (TS), and at different CS and TS intensities, respectively. Focal TMS invariably produced MEPs in both ipsilateral and contralateral lingual muscle,. MT was lower and MEP recruitment was steeper When recorded from the contralateral muscle group. ICI and ICF were identical in the ipsilateral and contralateral representations, with inhibition occurring at short ISIs (2 and 3 ms) and facilitation occurring at longer ISIs (10 and 15 ms). Moreover, changing one stimulus parameter regularly produced analogous changes in MEP size bilaterally, revealing strong linear cor-relations between ipsilateral and contralateral ICI and ICF (P < 0.0001). These findings indicate that the ipsilateral and contralateral representations of the tongue are under analogous inhibitory and facilitatory control, possibly by a common intracortical network. C1 NINCDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20892 USA. NINCDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Ludwig Boltzmann Inst Epilepsy & Neuromuscular Di, Vienna, Austria. JW Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany. RP Hallett, M (reprint author), NINCDS, Human Cortical Physiol Sect, NIH, Bldg 10,Rm 5N226,Ctr Dr MSC-1428, Bethesda, MD 20892 USA. NR 32 TC 34 Z9 34 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD NOV PY 2001 VL 18 IS 6 BP 550 EP 558 DI 10.1097/00004691-200111000-00005 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 508PK UT WOS:000173097500005 PM 11779968 ER PT J AU Katz, SI AF Katz, SI TI Dermatological research in the 21st century: Our fantastic future SO JOURNAL OF DERMATOLOGY LA English DT Article AB During the second half of the twentieth century, dermatology came of age. just as clinical dermatology, through new diagnostic and therapeutic modalities, matured to a point where the dermatologist could affect peoples' lives profoundly, so too did dermatological research enhance our understanding of skin diseases enormously. Dermatology should not be viewed as a scientific discipline-advances come from fundamental scientific areas such as cell and molecular biology, biochemistry, immunology, microbiology, technology, the clinical sciences and others. Thus, dermatology and skin biology live within a universe of science, only a small part of which is dermatology and skin biology, and our patients and our science are dependent on integration and interdigitation with the universe of science for future success. In this lecture I will elaborate on where I think the next 10-20 years will take us in this universe. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JAPANESE DERMATOLGICAL ASSOC PI TOKYO PA TAISEI-BLDG., 14-10 HONGO 3-CHOME, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0385-2407 J9 J DERMATOL JI J. Dermatol. PD NOV PY 2001 VL 28 IS 11 BP 599 EP 601 PG 3 WC Dermatology SC Dermatology GA 503QM UT WOS:000172811500003 PM 11770713 ER PT J AU Mendez, S Fernandez-Perez, FJ Santin, N De la Fuente, C Cuquerella, M Gomez-Munoz, MT Alunda, JM AF Mendez, S Fernandez-Perez, FJ Santin, N De la Fuente, C Cuquerella, M Gomez-Munoz, MT Alunda, JM TI Correlation between in vitro and in vivo infectivity of Leishmania infantum clones SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE canine leishmaniasis; clones; growth; hamsters; macrophages; protozoa; resistance; virulence; visceral leishmaniasis ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO; PROMASTIGOTES; MACROPHAGES; DONOVANI; VIRULENT; SENSITIVITY; TROPISM; STRAINS; SPAIN AB Eleven clones of a single strain of Leishmania infantum (NCAN/ES/88/ISS441, Doba) were analyzed for biological behavior in vivo and in vitro, Different clones showed differences in growth dependent upon the two culture media employed. All clones displayed only slight differences in H2O2 and NaNO2 sensitivity compared to the original strain, whereas in vitro infectivity For mouse peritoneal macrophages differed significantly among the clones. In vivo infections in hamsters correlated strongly with in vitro infectivity. The phenotypic differences found suggest a polyclonal structure fur the Leishmania infantum strain studied. C1 Univ Complutense Madrid, Fac Vet, Dept Patol Anim Sanidad Anim 1, Madrid 28040, Spain. NIAID, NIH, Bethesda, MD 20892 USA. RP Alunda, JM (reprint author), Univ Complutense Madrid, Fac Vet, Dept Patol Anim Sanidad Anim 1, Madrid 28040, Spain. RI Gomez_Munoz, Maria Teresa/S-3800-2016 OI Gomez_Munoz, Maria Teresa/0000-0001-8104-845X NR 34 TC 4 Z9 4 U1 0 U2 4 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD NOV-DEC PY 2001 VL 48 IS 6 BP 616 EP 621 DI 10.1111/j.1550-7408.2001.tb00200.x PG 6 WC Microbiology SC Microbiology GA 516VB UT WOS:000173576500002 PM 11831769 ER PT J AU Ribeiro, JMC Francischetti, IMB AF Ribeiro, JMC Francischetti, IMB TI Platelet-activating-factor-hydrolyzing phospholipase C in the salivary glands and saliva of the mosquito Culex quinquefasciatus SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE platelet activating factor; saliva; hematophagy; phospholipase C; mosquito; Culex quinquefasciatus ID GLYCERYL ETHER PHOSPHORYLCHOLINE; RHODNIUS-PROLIXUS; AEDES-AEGYPTI; BLOODSUCKING BUG; NITRIC-OXIDE; HEME PROTEIN; PAF-ACETHER; AGGREGATION; PURIFICATION; PATHWAY AB A phospholipase C activity specific for platelet-activating factor (PAF), named PAF phosphoryleholine hydrolase, was found in the salivary glands and saliva of the human-feeding mosquito Culex quinquefasciatus. The enzymatic activity was demonstrated by inhibition of PAF-induced platelet aggregation, and by identification of substrate consumption and production of diacyl glyceride by electrospray-ionisation mass spectrometry. The activity has a neutral optimal pH and an apparent molecular mass of 40-50 kDa. Two anthropophilic mosquito species, Aedes aegypti and Anopheles gambiae, do not have this salivary activity. The results are interpreted within the evolutionary context of the genera Culex, Aedes and Anopheles. C1 NIAID, Sect Med Entomol, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Ribeiro, JMC (reprint author), NIAID, Sect Med Entomol, Parasit Dis Lab, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. OI Ribeiro, Jose/0000-0002-9107-0818 NR 42 TC 15 Z9 18 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD NOV PY 2001 VL 204 IS 22 BP 3887 EP 3894 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 500UH UT WOS:000172644800007 PM 11807106 ER PT J AU Studer, SM Orens, JB Rosas, I Krishnan, JA Cope, KA Yang, S Conte, JV Becker, PB Risby, TH AF Studer, SM Orens, JB Rosas, I Krishnan, JA Cope, KA Yang, S Conte, JV Becker, PB Risby, TH TI Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; HEART-LUNG; OBLITERATIVE BRONCHIOLITIS; LIPID-PEROXIDATION; RISK-FACTORS; ANTIOXIDANT STATUS; OXIDATIVE STRESS; MANAGEMENT; REPERFUSION; METABOLISM AB Background: Obliterative bronchiolitis (OB) remains one of the leading causes of death in lung transplant recipients after 2 years, and acute rejection (AR) of lung allograft is a major risk factor for OB. Treatment of AR may reduce the incidence of OB, although diagnosis of AR often requires bronchoscopic lung biopsy. In this study, we evaluated the utility of exhaled-breath biomarkers for the non-invasive diagnosis of AR. Methods: We obtained breath samples from 44 consecutive lung transplant recipients who attended ambulatory follow-up visits for the Johns Hopkins Lung Transplant Program. Bronchoscopy within 7 days of their breath samples showed histopathology in 21of these patients, and we included them in our analysis. We measured hydrocarbon markers of pro-oxidant events (ethane and 1-pentane), isoprene, acetone, and sulfur-containing compounds (hydrogen sulfide and carbonyl sulfide) in exhaled breath and compared their levels to the lung histopathology, graded as stable (non-rejection) or AR. None of the study subjects were diagnosed with OB or infection at the time of the clinical bronchoscopy. Results: We found no significant difference in exhaled levels of hydrocarbons, acetone, or hydrogen sulfide between the stable and AR groups. However, we did find significant increase in exhaled carbonyl sulfide (COS) levels in AR subjects compared with stable subjects. We also observed a trend in 7 of 8 patients who had serial sets of breath and histopathology data that supported a role for COS as a breath biomarker of AR. Conclusions: This study demonstrated elevations in exhaled COS levels in subjects with AR compared with stable subjects, suggesting a diagnostic role for this non-invasive Z biomarker. Further exploration of breath analysis in lung transplant recipients is warranted to complement fiberoptic bronchoscopy and obviate the need for this procedure in some patients. C1 Johns Hopkins Med Inst, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. NHLBI, Bethesda, MD 20892 USA. RP Studer, SM (reprint author), CUNY, Mt Sinai Med Ctr, RMTI-Box 1104,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NHLBI NIH HHS [P01-HL56091] NR 28 TC 85 Z9 86 U1 3 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 2001 VL 20 IS 11 BP 1158 EP 1166 DI 10.1016/S1053-2498(01)00343-6 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 492LW UT WOS:000172170700004 PM 11704475 ER PT J AU Murphy, WJ Page, JE Smith, C Desrosiers, RC O'Brien, SJ AF Murphy, WJ Page, JE Smith, C Desrosiers, RC O'Brien, SJ TI A radiation hybrid mapping panel for the rhesus macaque SO JOURNAL OF HEREDITY LA English DT Article ID PRIMATE GENOME PROJECT; MAP; ORGANIZATION; CAT AB The genomes of nonhuman primates have recently become highly visible candidates for full genome analysis, as they provide powerful models of human disease and a better understanding of the evolution of the human genome. We describe the creation of a 5000 rad radiation hybrid (RH) mapping panel for the rhesus macaque. Duplicate genotypes of 84 microsatellite and coding gene sequence tagged sites from six macaque chromosomes produced an estimated whole genome retention frequency of 0.33. To test the mapping ability of the panel, we constructed RH maps for macaque chromosomes 7 and 9 and compared them to orthologous locus orders in existing human and baboon maps derived from different methodologies. Concordant marker order between all three species maps suggests that the current panel represents a powerful mapping resource for generating high-density comparative maps of the rhesus macaque and other species genomes. C1 NCI, Lab Genome Divers, FCRCD, Frederick, MD 21702 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Murphy, WJ (reprint author), NCI, Lab Genome Divers, FCRCD, Bldg 560,Rm 11-10, Frederick, MD 21702 USA. NR 17 TC 13 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD NOV-DEC PY 2001 VL 92 IS 6 BP 516 EP 519 DI 10.1093/jhered/92.6.516 PG 4 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 543TC UT WOS:000175116400013 PM 11948222 ER PT J AU Gerschenson, M Nguyen, VT St Claire, MC Harbaugh, SW Harbaugh, JW Proia, LA Poirier, MC AF Gerschenson, M Nguyen, VT St Claire, MC Harbaugh, SW Harbaugh, JW Proia, LA Poirier, MC TI Chronic stavudine exposure induces hepatic mitochondrial toxicity in adult Erythrocebus patas monkeys SO JOURNAL OF HUMAN VIROLOGY LA English DT Article DE skeletal muscle; oxidative phosphorylation; mitochondrial DNA; 2 ',3 '-didehydro-3 '-deoxythymidine; clinical chemistry ID LACTIC-ACIDOSIS; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; LIVER-FAILURE; NUCLEOSIDE; HYPERLACTATEMIA; STEATOSIS; ZIDOVUDINE; LAMIVUDINE; DRUGS AB Objectives: To understand the mitochondrial mechanisms underlying the lactic acidosis and hepatic steatosis seen in some HIV-1-infected individuals after long-term stavudine (d4T) exposure, we have explored mitochondrial integrity in adult monkeys (Erythrocebus patas) given a daily human equivalent dose of d4T for 78 days. Study Design/Methods: Three Erythrocebus patas (patas) monkeys were given 3 mg d4T orally twice daily (total 6 mg d4T), or approximately 1.2 mg d4T/kg body weight per day, for 78 days and compared with 3 unexposed animals. Blood taken from controls and from treated monkeys before and after drug exposure was subjected to a complete clinical chemistry profile. Liver and skeletal muscles were examined for oxidative phosphorylation enzyme specific activities, mitochondrial deoxyribonucleic acid (mtDNA) quantity by slot blot, and mtDNA integrity by Southern blot. Results: Clinical chemistry assays demonstrated few significant differences; however, one d4T-exposed monkey had a serum lactate of 8.1 mmol/L after 78 days of oral d4T ingestion. Specific activities of oxidative phosphorylation Complexes I, II, and IV were significantly altered in both livers and skeletal muscles from the d4T-exposed animals, compared with the controls (p less than or equal to 0.05). Significant depletion of mitochondrial DNA was observed in livers of drug-exposed monkeys, but not in skeletal muscle (p less than or equal to 0.05). Further examination of liver DNA by Southern blot confirmed hepatic mtDNA depletion in drug exposed animals. Conclusions: The data suggest that direct examination of the liver may be required to elucidate clinical d4T-induced hepatotoxicity related to mitochondrial damage. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. BioQual Inc, Rockville, MD USA. Rush Med Coll, Chicago, IL 60612 USA. RP Poirier, MC (reprint author), NCI, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Rm 2A05, Bethesda, MD 20892 USA. NR 37 TC 21 Z9 22 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD NOV-DEC PY 2001 VL 4 IS 6 BP 335 EP 342 DI 10.1097/01.GHV.000019968.51560.90 PG 8 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 574YF UT WOS:000176917500006 PM 12082400 ER PT J AU Svetkey, LP Moore, TJ Simons-Morton, DG Appel, LJ Bray, GA Sacks, FM Ard, JD Mortensen, RM Mitchell, SR Conlin, PR Kesari, M AF Svetkey, LP Moore, TJ Simons-Morton, DG Appel, LJ Bray, GA Sacks, FM Ard, JD Mortensen, RM Mitchell, SR Conlin, PR Kesari, M CA DASH Collaborative Res Grp TI Angiotensinogen genotype and blood pressure response in the Dietary Approaches to Stop Hypertension (DASH) study SO JOURNAL OF HYPERTENSION LA English DT Article DE angiotensin converting enzyme; angiotensinogen; blood pressure; DASH; diet; genetics; hypertension ID CONVERTING-ENZYME GENE; DEPENDENT DIABETES-MELLITUS; MYOCARDIAL-INFARCTION; SERUM ANGIOTENSINOGEN; INSERTION/DELETION POLYMORPHISM; DELETION POLYMORPHISM; MOLECULAR VARIANT; AFRICAN-AMERICANS; CLINICAL-TRIAL; ASSOCIATION AB Objective To determine the relationship between angiotensinogen (ANG) genotype and blood pressure response to the dietary patterns of the Dietary Approaches to Stop Hypertension (DASH) trial. The angiotensin converting enzyme (ACE) gene was also tested. Design The DASH trial was a randomized outpatient feeding study comparing the effects on blood pressure (BP) of three dietary patterns: a control diet, similar to typical American intake; a 'fruits and vegetables' diet (F/V) that is rich in fruits and vegetables but otherwise resembles the control diet; and the DASH diet that is reduced in fats and that emphasizes fruits, vegetables and low-fat dairy products. Participants' genotype was also determined. Setting Four clinical sites. Participants Adults with above-optimal BP or stage I hypertension. Intervention Participants ate one of the three dietary patterns for 8 weeks. Sodium intake and weight were held constant. In 356 of 459 DASH participants, DNA was extracted from leukocytes and genotyped for the G-6A ANG polymorphism and the D/I ACE polymorphism, by the polymerase chain reaction. Main outcomes Genotype at ANG and ACE loci; BP after 8 weeks of intervention diet. Results There was no association between ACE genotype and BP response. Associations with ANG polymorphism were significant: net systolic and diastolic BP response to the DASH diet was greatest in individuals with the AA genotype (-6.93/-3.68 mmHg) and least in those with the GG genotype (-2.80/0.20 mmHg). A similar relationship existed for the F/V diet. Conclusions ANG genotype is associated with BP response to the DASH diet The AA genotype confers excess risk of hypertension and is associated with increased responsiveness to diet. (C) 2001 Lippincott Williams & Wilkins. C1 Duke Hypertens Ctr, Durham, NC 27705 USA. Duke Univ, Med Ctr, Sarah W Stedman Ctr Nutrit Studies, Durham, NC USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrine Hypertens, Boston, MA 02115 USA. Merck & Co Inc, Boston, MA USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Welch Ctr Prevent, Baltimore, MD USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70803 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. RP Svetkey, LP (reprint author), Duke Hypertens Ctr, 3020 Pickett Rd, Durham, NC 27705 USA. FU NCRR NIH HHS [MO1 RR02636, RR00722, RR02635]; NHLBI NIH HHS [U01-HL50981, P50 HL55000, U01-HL50968, U01-HL50972, U01-HL50977, U01-HL50982] NR 50 TC 52 Z9 53 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD NOV PY 2001 VL 19 IS 11 BP 1949 EP 1956 DI 10.1097/00004872-200111000-00004 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 489KG UT WOS:000171990100004 PM 11677359 ER PT J AU Snyder, DS Small, PLC AF Snyder, DS Small, PLC TI Staining of cellular mitochondria with LDS-751 SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE mitochondria; LDS-751; staining; confocal microscopy ID APOPTOSIS; RHODAMINE-123; CELLS AB We have found the dye LDS-751 to bind almost exclusively to mitochondria when incubated with viable, nucleated cells. Treatment of cells with the nuclear stain acridine orange and LDS-751 revealed little colocalization when the cells were examined by confocal microscopy. Staining with the dye rhodamine 123, which is known to bind polarized mitochondria, was virtually identical to the pattern observed with LDS-751. This staining pattern was observed to be consistent over a range of 0.02-20 mug/ml LDS-751 and was consistent between both fibroblasts and monocytes. Depolarization of mitochondria with the mitochondrial depolarizing agents phenyl arsine oxide and carbonyl cyanide m-chlorophenylhydrazone (CCCP) dramatically reduced both LDS-751 staining, and rhodamine 123 fluorescence. Taken together, these results suggest that LDS-751 is excluded from the nucleus and binds the polarized membranes of mitochondria. Given this, interpretation of LDS-751 fluorescence as being indicative of nuclear status, as is commonly done to discriminate between leukocytes and erythrocytes, is unwarranted and may lead to erroneous conclusions if mitochondria become depolarized upon processing. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Snyder, DS (reprint author), NIAID, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 10 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD NOV 1 PY 2001 VL 257 IS 1-2 BP 35 EP 40 DI 10.1016/S0022-1759(01)00440-9 PG 6 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 489JT UT WOS:000171988800003 PM 11687236 ER PT J AU Spence, SE Lohrey, NC Ortiz, M Gooya, J Keller, JR AF Spence, SE Lohrey, NC Ortiz, M Gooya, J Keller, JR TI Detection of growth factor receptor RNA in individual hematopoietic cells by in situ RT-PCR; comparison with RT-PCR SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE hematopoiesis; receptors; stem cells; gene expression; in situ RT-PCR ID POLYMERASE CHAIN-REACTION; COLONY-STIMULATING FACTOR; MESSENGER-RNA; STEM-CELLS; GENE-EXPRESSION; DIFFERENTIATION; INTERLEUKIN-3; CYTOKINE; INVITRO; LIVER AB The ability to detect changes in RNA expression in single cells would greatly enhance understanding of the molecular basis of biological responses to positive and negative growth regulators. To this end, we compared expression of RNA encoding the receptors for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, leukemia inhibitory factor (LIF) and stem cell factor (SCF) in populations of primitive hematopoietic progenitors (lineage marker negative, Lin(-), and Lin(-) c-Kit(+)) by RT-PCR and in situ RT-PCR. Both Lin(-) and Lin(-) c-Kit(+) progenitors expressed all receptors by RT-PCR. However, RT-PCR could not distinguish between the possibility that all cells expressed growth factor receptor RNA, or the possibility that only a proportion of cells expressed RNA. Therefore, we used in situ RT-PCR to examine growth factor receptor mRNA expression in individual cells. In contrast to RT-PCR, we observed that only 40-80% of Lin(-) cells and 75-100% of Lin(-) c-Kit(+) cells were positive for expression of the growth factor receptor subunits, demonstrating that not all cells were receptor positive. We found that in situ RT-PCR could also be used to measure induction or repression of receptor RNA expression in these cell populations. Specifically, the percentage of cells expressing IL-6 alpha receptor RNA decreased from 88% positive in freshly harvested cells to 9% in Lin(-) c-Kit(+) cells cultured in IL-3 for 18 h. Thus, in situ RT-PCR can be used to detect and quantify the number of individual cells that express growth factor receptor mRNA, and may also be useful to measure changes in expression of other endogenous genes or genes introduced by transfection and gene therapy vectors. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NCI, Intramural Res Support Program, SAIC Frederick, Div Basic Sci, Frederick, MD 21702 USA. NCI, Lab Leukocyte Biol, Div Basic Sci, Frederick, MD 21702 USA. RP Spence, SE (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Div Basic Sci, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 22 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD NOV 1 PY 2001 VL 257 IS 1-2 BP 123 EP 136 DI 10.1016/S0022-1759(01)00457-4 PG 14 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 489JT UT WOS:000171988800013 PM 11687246 ER PT J AU Wu, MT Fang, H Hwang, ST AF Wu, MT Fang, H Hwang, ST TI Cutting edge: CCR4 mediates antigen-primed T cell binding to activated dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ADHESION RECEPTORS; IMMUNE-RESPONSES; LANGERHANS CELLS; IN-VITRO; CHEMOKINE; LYMPHOCYTES; SKIN; CHEMOATTRACTANT; ENGAGEMENT; SUBSETS AB The binding of a T cell to an Ag-laden dendritic cell (DC) is a critical step of the acquired immune response. Herein, we address whether a DC-produced chemokine can induce the arrest of T cells on DC under dynamic flow conditions. Ag-primed T cells and a T cell line were observed to rapidly (similar to0.5 s) bind to immobilized DC at low shear stress (0.1-0.2 dynes/cm(2)) in a pertussis toxin-sensitive fashion. Quantitatively, Ag-primed T cells displayed 2- to 3-fold enhanced binding to DC compared with unprimed T cells (p < 0.01). In contrast to naive T cells, primed T cell arrest was largely inhibited by pertussis toxin, neutralization of the CC chemokine, macrophage-derived chemokine (CCL22), or by desensitization of the CCL22 receptor, CCR4. Our results demonstrate that DC-derived CCL22 induces rapid binding of activated T cells under dynamic conditions and that Ag-primed and naive T cells fundamentally differ with respect. to chemokine-dependent binding to DC. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NCI, Dermatol Branch, Bldg 10,Room 12N246,10 Ctr Dr, Bethesda, MD 20892 USA. NR 32 TC 30 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2001 VL 167 IS 9 BP 4791 EP 4795 PG 5 WC Immunology SC Immunology GA 487DN UT WOS:000171858500001 PM 11673480 ER PT J AU Curiel, RE Garcia, CS Farooq, L Aguero, MF Espinoza-Delgado, I AF Curiel, RE Garcia, CS Farooq, L Aguero, MF Espinoza-Delgado, I TI Bryostatin-1 and IL-2 synergize to induce IFN-gamma expression in human peripheral blood T cells: Implications for cancer immunotherapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-C; TUMOR-BEARING MICE; INTERFERON-GAMMA; MESSENGER-RNA; PHORBOL ESTERS; IN-VIVO; ACTIVATOR BRYOSTATIN-1; ANTICANCER AGENT; GENE-EXPRESSION; HUMAN MONOCYTES AB Bryostatin-1 (Bryo-1), a protein kinase C modulator with antineoplastic activity, may exert some of its antitumor activity through activation of the immune response. Studies in tumor-bearing hosts have indicated that the T cell response, particularly IFN-gamma production, is impaired. To evaluate whether Bryo-1 plus IL-2 may affect the activation pattern of T cells, we investigated the expression of IFN-gamma mRNA and protein in human primary T cells. Northern blot analysis and ELISAs demonstrated that Bryo-1 and IL-2 synergized to induce both IFN-gamma mRNA and protein expression. This synergistic induction was seen within 3 h of treatment and with as little as 10 U/ml IL-2 and 1.0 ng/ml Bryo-1. In vitro transcription assays revealed that Bryo-1 plus IL-2 induced transcriptional activation of the IFN-gamma gene. Furthermore, mRNA stability studies indicated that this treatment also enhanced the IFN-gamma mRNA half-life. Both CD4(+) and CD8(+) T cells responded to the treatment with IFN-gamma expression. The induction of the IFN-gamma expression was decreased by a specific p38 mitogen-activated protein kinase inhibitor, but not by a protein kinase C inhibitor. Our results demonstrate for the first time that Bryo-1 in combination with IL-2 control IFN-gamma gene expression at both the transcriptional and post-transcriptional levels through a p38 mitogen-activated protein kinase-dependent process. Given the pivotal role that IFN-gamma plays in the orchestration of an effective Th1 type of response, our results suggest that Bryo-1 plus IL-2 may be a valuable combined therapy for cancer treatment. C1 Louisiana State Univ, Med Ctr, Dept Med, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA. RP Espinoza-Delgado, I (reprint author), NIA, Gerontol Res Ctr, Hematol Oncol Sect, 5600 Nathan Shock Dr,Room 4C10, Baltimore, MD 21224 USA. FU NCI NIH HHS [CA83632] NR 68 TC 23 Z9 24 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2001 VL 167 IS 9 BP 4828 EP 4837 PG 10 WC Immunology SC Immunology GA 487DN UT WOS:000171858500007 PM 11673486 ER PT J AU Horikawa, K Kaku, H Nakajima, H Davey, HW Henninghausen, L Iwamoto, I Yasue, T Kariyone, A Takatsu, K AF Horikawa, K Kaku, H Nakajima, H Davey, HW Henninghausen, L Iwamoto, I Yasue, T Kariyone, A Takatsu, K TI Essential role of Stat5 for IL-5-dependent IgH switch recombination in mouse B cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; RECEPTOR-ALPHA CHAIN; IMMUNOGLOBULIN CLASS SWITCH; INTERLEUKIN-5 IL-5; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; CD38 LIGATION; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODY; CYTOPLASMIC DOMAIN AB IL-5 stimulation of CD38-activated murine splenic B cells induces mu-gammal CSR at the DNA level leading to a high level of IgG1 production. Further addition of IL-4 in the system enhances IL-5-dependent mu-gammal CSR. Although some of the postreceptor signaling events initiated by IL-5 in activated B cells have been characterized, the involvement of Stat in IL-5 signaling has not been thoroughly evaluated. In this study, we examined the activation of Stat5 and activation-induced cytidine deaminase (AID) in CD38-activated murine splenic B cells by IL-5. The role of Stat5a and Stat5b in IL-5-induced mu-gammal CSR and also IgG1 and IgM production was documented, as IL-5 does not act on CD38-stimulated splenic B cells from Stat5a(-/-) and Stat5b(-/-) mice. Expression levels of CD38-induced germline gamma1 transcripts and AID in Stat5a-/- and Stat5b-/- B cells upon IL-5 stimulation were comparable to those of wild-type B cells. The impaired mu-gammal CSR by Stat5b-/- B cells, but not by Stat5a-/- B cells, was rescued in part by IL-4, as the addition of IL-4 to the culture of CD38- and IL-5-stimulated B cells induced mu-gammal CSR leading to IgG1 production. Analysis of cell division cycle number of wild-type B cells revealed that mu-gammal CSR was observed after five or six cell divisions. Stat5a(-/-) and Stat5b(-/-) B cells showed similar cell division cycles, but they did not undergo mu-gammal CSR. Our data support the notion that both Stat5a and Stat5b are essential for IL-5-dependent mu-gammal CSR and Ig secretion; however, their major target may not be AID. Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function. C1 Univ Tokyo, Inst Med Sci, Dept Immunol, Minato Ku, Tokyo 1088639, Japan. Chiba Univ, Sch Med, Dept Internal Med 2, Chiba 280, Japan. AgRes, Hamilton, New Zealand. NIDDKD, Bethesda, MD USA. RP Takatsu, K (reprint author), Univ Tokyo, Inst Med Sci, Dept Immunol, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. EM takatsuk@ims.u-tokyo.ac.jp NR 69 TC 24 Z9 24 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2001 VL 167 IS 9 BP 5018 EP 5026 PG 9 WC Immunology SC Immunology GA 487DN UT WOS:000171858500031 PM 11673510 ER PT J AU Packard, BZ Komoriya, A Brotz, TM Henkart, PA AF Packard, BZ Komoriya, A Brotz, TM Henkart, PA TI Caspase 8 activity in membrane blebs after anti-Fas ligation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID APOPTOSIS; LYMPHOCYTES; CLEAVAGE; DAMAGE AB Previous studies of thymocyte apoptosis using a series of cell-permeable fluorogenic peptide substrates showed that Fas crosslinking triggered a caspase cascade in which cleavage of the IETDase (caspase 8-selective) substrate was the earliest caspase activity measured by flow cytometry. This result was expected in light of the abundant evidence for caspase 8 activation as an initiating event in the Fas death pathway. However, when apoptosis was induced by anti-Fas in CTL and the caspase cascade examined by this approach, IETDase activation followed increases in LEHDase, YVHDase, and VEIDase activities (selective for caspases 9, 1, and 6, respectively). When examined by confocal microscopy, anti-Fas-treated CTL showed the early appearance of IETDase-containing plasma membrane vesicles and their release from the CTL surface, followed by activation of other caspase activities in the cell interior. Since these vesicles were not included in the flow cytometry analysis, the early IETDase activity had been underestimated. In contrast to anti-Fas, induction of apoptosis in these CTL by IL-2 withdrawal resulted in early IETDase activity in the cytoplasm, with no plasma membrane vesiculation. Thus, anti-Fas-induced initiation of caspase activity at the plasma membrane may In some cells result in local proteolysis of submembrane proteins, leading to generation of membrane vesicles that are highly enriched in active caspase 8. C1 NCI, Expt Immunol Branch, NHI, Bethesda, MD 20892 USA. Oncolmmunin Inc, Gaithersburg, MD 20877 USA. RP Henkart, PA (reprint author), NCI, Expt Immunol Branch, NHI, Bldg 10,Rm 4B36, Bethesda, MD 20892 USA. RI Brotz, Tilmann/R-6599-2016 OI Brotz, Tilmann/0000-0001-8212-459X NR 16 TC 24 Z9 25 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2001 VL 167 IS 9 BP 5061 EP 5066 PG 6 WC Immunology SC Immunology GA 487DN UT WOS:000171858500036 PM 11673515 ER PT J AU Mocellin, S Fetsch, T Abati, T Phan, GQ Wang, J Provenzano, M Stroncek, D Rosenberg, SA Marincola, FM AF Mocellin, S Fetsch, T Abati, T Phan, GQ Wang, J Provenzano, M Stroncek, D Rosenberg, SA Marincola, FM TI Laser scanning cytometry evaluation of MART-1, gp100, and HLA-A2 expression in melanoma metastases SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma; MART-1; gp100; HLA; laser scanning cytometer ID CYTOTOXIC T-LYMPHOCYTES; DNA FLOW-CYTOMETRY; CLASS-I; IMMUNOPHENOTYPIC ANALYSIS; PROGNOSTIC-SIGNIFICANCE; CELL-LINES; RECOGNITION; LESIONS; BENIGN; TUMORS AB Assessment of antigen expression by solid tumors has relied predominantly on immunohistochemistry, flow cytometry, and more recently quantitative realtime polymerase chain reaction. However, all these techniques present intrinsic limits. The laser scanning cytometer, by combining the properties of light and fluorescence microscopy with those of laser cytometry, can quantitatively and objectively analyze hypocellular samples such as fine-needle aspirates on an individual cell basis. To validate the fidelity of laser scanning cytometry for quantitative immunophenotyping of fine-needle aspirates, the authors measured the expression of the melanoma-associated antigens MART-1 and P100 as well as HLA-A2, a HLA class 1 restriction element associated with their recognition by melanoma-specific T cells. Expression of melanoma antigens and HLA was measured by laser scanning cytometry and immunohistochemistry in fine-needle aspirates from melanoma metastases. In addition, transcription levels of both melanoma antigens were recorded by quantitative real-time polymerase chain reaction. A quantity of less than 1,000 cells per sample (average 682 cells) was sufficient for the analysis. Laser scanning cytometry estimates correlated with those of immunohistochemistry and quantitative real-time polymerase chain reaction for MART-1 and gp100. A good correlation in HLA-A2 detection by laser scanning cytometry and immunohistochemistry was also observed. Moreover, the laser scanning cytometer could discriminate subsets of cells from the same lesion with heterogeneous melanoma antigen expression, leading to the observation that cells with a DNA index greater than 2.5 expressed significantly less gp100. Thus, laser scanning cytometry yields detailed information on protein expression in individual cells and represents a new tool for dissecting the immune response in the tumor microenvironment. C1 NCI, Surg Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Cytopathol Sect, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Ctr Clin, NIH, Bldg 10,Room 2B42,10 Ctr Dr MSC 1502, Bethesda, MD 20892 USA. NR 36 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2001 VL 24 IS 6 BP 447 EP 458 DI 10.1097/00002371-200111000-00002 PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 494LE UT WOS:000172283300002 PM 11759068 ER PT J AU Cortez, KJ Erdman, DD Peret, TCT Gill, VJ Childs, R Barrett, AJ Bennett, JE AF Cortez, KJ Erdman, DD Peret, TCT Gill, VJ Childs, R Barrett, AJ Bennett, JE TI Outbreak of human parainfluenza virus 3 infections in a hematopoietic stem cell transplant population SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; MOLECULAR EPIDEMIOLOGY; MARROW TRANSPLANTATION; RAPID DIAGNOSIS; RECIPIENTS; TYPE-3; ADULTS; WARD AB Clinical manifestations and epidemiological features are described for a cluster of 12 cases of human parainfluenza virus 3 (HPIV3) infection that occurred among 64 allogeneic hematopoietic stem cell transplant (SCT) recipients in an 11-week period during spring 2000. Upper respiratory symptoms predominated. Pneumonia occurred in 3 patients and was a contributing factor in the death of 1 patient. Exposure histories and molecular analysis of HPIV3 isolates suggested that both community acquired and nosocomially transmitted infections occurred during this outbreak. A chain of transmission within the outpatient clinic appeared to have occurred in 4 outpatients and to have extended to 2 hospitalized patients. Molecular epidemiology was useful in discerning routes of transmission in this outbreak. C1 NIAID, Clin Invest Lab, Clin Mycol Sect, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA. NHLBI, NIH, Hematol Branch, Stem Cell Allotransplant Unit, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Resp & Enter Viruses Branch, Atlanta, GA USA. RP Bennett, JE (reprint author), NIH, Ctr Clin, Rm 11C304, Bethesda, MD 20892 USA. EM jb46y@nih.gov NR 24 TC 53 Z9 54 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2001 VL 184 IS 9 BP 1093 EP 1097 DI 10.1086/322041 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 482EC UT WOS:000171561000001 PM 11598830 ER PT J AU Coombs, RW Wright, DJ Reichelderfer, PS Burns, DN Cohn, J Cu-Uvin, S Baron, PA Cohen, MH Landay, AL Lewis, S Kovacs, A AF Coombs, RW Wright, DJ Reichelderfer, PS Burns, DN Cohn, J Cu-Uvin, S Baron, PA Cohen, MH Landay, AL Lewis, S Kovacs, A CA Womens Hlth Study 001 Team TI Variation of human immunodeficiency virus type 1 viral RNA levels in the female genital tract: Implications for applying measurements to individual women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BLOOD; HIV-1; LOAD; SECRETIONS AB The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at greater than or equal to1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P < .001) or with concomitant genital tract infection (P = .003). Endocervical canal wicks should be considered as an adjunct to cervicovaginal lavage, to improve the sensitivity and precision of HIV-1 RNA detection. C1 Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. Univ Washington, Dept Med, Seattle, WA 98104 USA. NIH, Bethesda, MD 20892 USA. Wayne State Univ, Detroit, MI 48202 USA. Miriam Hosp, Providence, RI 02906 USA. Columbia Univ Coll Phys & Surg, St Lukes Roosevelt Hosp Ctr, New York, NY 10032 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ So Calif, Los Angeles, CA 90089 USA. RP Coombs, RW (reprint author), Univ Washington, Dept Lab Med, Box 359690, Seattle, WA 98104 USA. EM bcoombs@u.washington.edu FU NIAID NIH HHS [AI-27664, AI-30731]; NICHD NIH HHS [HD-33162] NR 15 TC 52 Z9 52 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2001 VL 184 IS 9 BP 1187 EP 1191 DI 10.1086/323660 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 482EC UT WOS:000171561000014 PM 11598843 ER PT J AU Goedert, JJ Hatzakis, A Sherman, KE Eyster, ME AF Goedert, JJ Hatzakis, A Sherman, KE Eyster, ME CA Multicenter Hemophila Cohort Study TI Lack of association of hepatitis C virus load and genotype with risk of end-stage liver disease in patients with human immunodeficiency virus coinfection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NATURAL-HISTORY; INFECTION; HEMOPHILIACS; COHORT; RNA AB In hepatitis C virus (HCV) infection, virus load and the risk for HCV-related end-stage liver disease (ESLD) are increased among persons with human immunodeficiency virus (HIV) coinfection. To clarify these relationships, 42 hemophilic patients who developed ESLD and random samples from 164 hemophilic patients with HCV infection alone and 146 with HCV-HIV coinfection were tested for HCV load and genotype. HCV genotype was unrelated to HIV and age. In contrast, HCV load was higher with older age (P(trend) = .0001) and with HIV coinfection (6.2 vs. 5.9 log(10) genome equivalents/mL, P = .0001). During 16 years of follow- up of dually infected patients, ESLD risk was unrelated to HCV load overall (P(trend) = .64) or separately to HCV genotype 1 and genotypes 2 or 3 (P(trend) greater than or equal to .70). Irrespective of virus load, incidence of ESLD was marginally increased 2-fold (95% confidence interval, 0.8-5.6) with HCV genotype 1. Understanding the discordance between HCV load and ESLD, despite HIV's link to each of these, may help clarify the pathogenesis of HCV-related disease. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD USA. Univ Cincinnati, Med Ctr, Div Digest Dis, Cincinnati, OH 45267 USA. Penn State Univ, Coll Med, Div Hematol Oncol, Dept Med, Hershey, PA 17033 USA. Univ Athens, Dept Hyg & Epidemiol, Natl Retrovirus Reference Ctr, Athens, Greece. RP Goedert, JJ (reprint author), 6120 Execut Blvd,Ste 8012,MSC 7248, Rockville, MD 20852 USA. EM GoedertJ@mail.nih.gov FU NCI NIH HHS [CP-33002] NR 15 TC 31 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2001 VL 184 IS 9 BP 1202 EP 1205 DI 10.1086/323665 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 482EC UT WOS:000171561000017 PM 11598846 ER PT J AU Cecil, JA Howell, MR Tawes, JJ Gaydos, JC McKee, KT Quinn, TC Gaydos, CA AF Cecil, JA Howell, MR Tawes, JJ Gaydos, JC McKee, KT Quinn, TC Gaydos, CA TI Features of Chlamydia trachomatis and Neisseria gonorrhoeae infection in male army recruits SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LIGASE CHAIN-REACTION; MILITARY RECRUITS; URINE; DISEASE; URETHRITIS; MEN AB Non-health care-seeking male United States Army recruits were tested for Chlamydia trachomatis (n = 2245) and Neisseria gonorrhoeae (n = 884), using a urine ligase chain reaction test to determine prevalence and potential risk factors for infection. The prevalence of chlamydial infection was 5.3%. Black race, a new sex partner, a history of trichomonas, and the presence of symptoms were associated with chlamydial infection. The prevalence of N. gonorrhoeae infection was 0.6%. Only a reported history of or positive test for C. trachomatis was associated with gonorrheal infection. Of those testing positive for chlamydia, 14% reported symptoms versus 40% of those with gonorrhea. Younger age was not a predictor of either infection, as has been shown for women. A substantial number of male army recruits are infected with C. trachomatis, but few are infected with N. gonorrhoeae. Screening on the basis of symptoms alone would miss the majority of both infections. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. Dept Def Global Emerging Infect Surveillance, Silver Spring, MD USA. HM Jackson Fdn, Rockville, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Womack Army Med Ctr, Ft Bragg, NC USA. RP Gaydos, CA (reprint author), 1159 Ross Bldg,720 Rutland St, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 15 TC 60 Z9 63 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2001 VL 184 IS 9 BP 1216 EP 1219 DI 10.1086/323662 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 482EC UT WOS:000171561000020 PM 11598849 ER PT J AU Savory, J Ghribi, O Forbes, MS Herman, MM AF Savory, J Ghribi, O Forbes, MS Herman, MM TI Aluminium and neuronal cell injury: inter-relationships between neurofilamentous arrays and apoptosis SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 4th Keele Meeting on Aluminium CY FEB 25-27, 2001 CL ENGLAND ID INDUCED NEUROFIBRILLARY TANGLES; AMYOTROPHIC-LATERAL-SCLEROSIS; ALZHEIMERS-DISEASE; CYTOCHROME-C; PERMEABILITY TRANSITION; BRAIN INJURY; TAU; IMMUNOREACTIVITY; DEGENERATION; RELEASE C1 Univ Virginia, Dept Pathol, Hlth Sci Ctr, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. NIMH, IRP, NIH, Bethesda, MD 20892 USA. RP Savory, J (reprint author), Univ Virginia, Dept Pathol, Hlth Sci Ctr, Box 168, Charlottesville, VA 22908 USA. NR 34 TC 27 Z9 31 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD NOV PY 2001 VL 87 IS 1-2 BP 15 EP 19 DI 10.1016/S0162-0134(01)00309-9 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 499TB UT WOS:000172585500004 PM 11709208 ER PT J AU Lange-Asschenfeldt, B Velasco, P Streit, M Hawighorst, T Pike, SE Tosato, G Detmar, M AF Lange-Asschenfeldt, B Velasco, P Streit, M Hawighorst, T Pike, SE Tosato, G Detmar, M TI The angiogenesis inhibitor vasostatin does not impair wound healing at tumor-inhibiting doses SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE calreticulin; cancer; endothelium; tissue repair ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-VESSEL MATURATION; ENDOGENOUS INHIBITOR; VASCULAR DEVELOPMENT; FACTOR EXPRESSION; TRANSGENIC MICE; SKIN; CALRETICULIN; ENDOSTATIN; THROMBOSPONDIN-2 AB Inhibition of tumor angiogenesis represents a promising new approach for the treatment of human cancers. It has remained unclear, however, whether inhibition of tumor angiogenesis may also result in impaired wound healing, a process thought to be angiogenesis dependent. To determine the effects of the angiogenesis inhibitor vasostatin, a 180 amino acid calreticulin fragment, on wound healing at tumor inhibiting doses, full-thickness wounds were generated on the back of nude mice that were also injected intradermally with CA46 Burkitt lymphoma cells. Mice were treated with daily injections of vasostatin or vehicle control at a site between the wounds and the transplanted tumor cells over 14 d. Vasostatin potently inhibited tumor growth and significantly reduced tumor angiogenesis, as measured by computer-assisted image analysis of CD31-stained tumor sections. Moreover, vasostatin treatment resulted in an increased fraction of mature tumor-associated blood vessels. In contrast, no impairment of wound healing was observed in vasostatin-treated mice, despite a significantly reduced vascularity of the wound granulation tissue. Our results reveal a different sensitivity of malignant tumor growth and physiologic wound healing to inhibition of angiogenesis, and they suggest that therapeutic inhibition of tumor angiogenesis may be achieved without impairment of tissue repair. C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Bldg 149,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [CA69184, CA86410] NR 38 TC 31 Z9 34 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2001 VL 117 IS 5 BP 1036 EP 1041 DI 10.1046/j.0022-202x.2001.01519.x PG 6 WC Dermatology SC Dermatology GA 492ZX UT WOS:000172198500002 PM 11710910 ER PT J AU Suzuki, H Kalair, W Shivji, GM Wang, BH Toto, P Amerio, P Kraemer, KH Sauder, DN AF Suzuki, H Kalair, W Shivji, GM Wang, BH Toto, P Amerio, P Kraemer, KH Sauder, DN TI Impaired ultraviolet-B-induced cytokine induction in xeroderma pigmentosum fibroblasts SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE DNA repair; photoimmunology; skin cancer ID NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; DELAYED-TYPE HYPERSENSITIVITY; DNA-REPAIR GENE; HUMAN KERATINOCYTES; SKIN-CANCER; TRANSCRIPTION FACTOR; MALIGNANT-MELANOMA; IN-VIVO; UV AB Xeroderma pigmentosum is a rare, autosomal recessive disease in which patients develop excessive solar damage at an early age and have a 1000-fold increased risk of developing cutaneous neoplasms. Xeroderma pigmentosum can be classified into seven complementation groups (A-G) with defects in different DNA nucleotide excision repair genes. Xeroderma pigmentosum patients also have impaired immune function including reduced natural killer cell activity and impaired induction of interferon-gamma. We hypothesized that altered cytokine induction may contribute to the immune defect in xeroderma pigmentosum patients. We examined cytokine mRNA expression after ultraviolet B irradiation using reverse transcriptase polymerase chain reaction in fibroblasts derived from five xeroderma pigmentosum patients in complementation groups A, C, and D and in complemented XP-A and XP-D cells. Cytokines interleukin-lp and interleukin-6 displayed impaired ultraviolet B induction whereas interleukin-8 had normal induction in the xeroderma pigmentosum fibroblasts. Stable complementation of XP-A and XP-D cell lines increased ultraviolet-B-induced interleukin-lp and interleukin-6 expression. These results demonstrate a deficient response of xeroderma pigmentosum fibroblasts to ultraviolet B in terms of cytokine interleukin-lo and interleukin-6 induction but normal interleukin-8 induction and exhibit a role for DNA repair in cytokine induction. C1 Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Div Dermatol, Toronto, ON, Canada. Univ G DAnnunzio, Chieti, Italy. Univ Ancona, Dept Dermatol, Ancona, Italy. NCI, Basic Res Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA. RP Kraemer, KH (reprint author), NCI, Basic Res Labs, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. OI AMERIO, Paolo/0000-0003-1589-9672 FU Intramural NIH HHS [Z01 BC004517-31] NR 49 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2001 VL 117 IS 5 BP 1151 EP 1155 DI 10.1046/j.0022-202x.2001.01525.x PG 5 WC Dermatology SC Dermatology GA 492ZX UT WOS:000172198500018 PM 11710926 ER PT J AU Harvat, BL Jetten, AM AF Harvat, BL Jetten, AM TI Decreased growth inhibitory responses of squamous carcinoma cells to interferon-gamma involve failure to recruit cki proteins into cdk2 complexes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE keratinocyte; p27(Kip1); p21 (WAF1/Cip1); p130 ID HUMAN EPIDERMAL-KERATINOCYTES; MAMMARY EPITHELIAL-CELLS; CYCLIN-DEPENDENT KINASES; GENE-EXPRESSION; RETINOBLASTOMA FAMILY; IRF-1 EXPRESSION; E7 ONCOPROTEIN; LUNG-CARCINOMA; DIFFERENTIATION; P27(KIP1) AB Interferon-gamma induces an irreversible growth arrest and squamous differentiation in normal human epidermal keratinocytes. We present for the first time a careful biochemical analysis of the cell-cycle-related events that occur during interferon-gamma treatment of normal human epidermal keratinocytes. The interferon-gamma -induced irreversible growth arrest state is characterized by inhibition of cyclin-dependent kinases, prevention of Rb and p130 (Rb2) phosphorylation, and increases in p27(Kip1), p16(Ink4a), and p130 proteins, together with a transient increase in p21(Waf1/Cip1). Cells derived from squamous cell carcinomas are less responsive to interferon-gamma and do not terminally differentiate. We exploited these differences in response to interferon-gamma in order to identify the particular molecular defects in cell cycle control that promote carcinogenesis in squamous epithelia. In several squamous cell carcinoma cell lines as well as in interferon-gamma -insensitive HaCaT cells, interferon gamma was unable to significantly induce levels of p130 and/or p16 protein. In addition, p21 association with cdk2 complexes was undetectable in either the absence or the presence of interferon-gamma and, unlike normal human epidermal keratinocytes, p27 association with cdk2 did not increase with interferon-gamma treatment. These multiple defects appear to be intrinsic to the mechanisms of cell cycle regulation rather than due to defects in the interferon-ly signaling pathway, as induction of several interferon-gamma -responsive genes including Stat 1, IRF-1, and p21 itself was normal. Interestingly, exogenous expression of p21 protein in the squamous cell carcinoma cell lines by adenovirus carrying wildtype p53 or p21 cDNA cooperated with interferon-gamma to produce a greater inhibition of growth than either agent alone, even though p21 protein could barely be detected in cdk2 complexes. We conclude that squamous cell carcinoma cells have intrinsic defects in their ability to regulate cdk-cki complexes in response to differentiation signals. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, LSRC, Durham, NC 27710 USA. Natl Inst Environm Hlth Sci, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC USA. RP Harvat, BL (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, LSRC, Box 3813, Durham, NC 27710 USA. OI Jetten, Anton/0000-0003-0954-4445 FU NIEHS NIH HHS [1K22ES00343-01] NR 56 TC 12 Z9 12 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2001 VL 117 IS 5 BP 1274 EP 1281 DI 10.1046/j.0022-202x.2001.01495.x PG 8 WC Dermatology SC Dermatology GA 492ZX UT WOS:000172198500036 PM 11710944 ER PT J AU Becker, KG Barnes, KC AF Becker, KG Barnes, KC TI Underlying disease specificity of genetic loci in atopic dermatitis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID SUSCEPTIBILITY LOCUS; AUTOIMMUNE-DISEASE; ENCEPHALOMYELITIS C1 NIA, Gerontol Res Ctr, DNA Array Unit, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. RP Becker, KG (reprint author), NIA, Gerontol Res Ctr, DNA Array Unit, NIH, Room 4-D16,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Becker, Kevin/0000-0002-6794-6656 NR 14 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2001 VL 117 IS 5 BP 1325 EP 1327 DI 10.1046/j.0022-202x.2001.01559.x PG 3 WC Dermatology SC Dermatology GA 492ZX UT WOS:000172198500046 PM 11710954 ER PT J AU Kirschstein, RL AF Kirschstein, RL TI Ruth L. Kirschstein, MD SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Kirschstein, RL (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD NOV PY 2001 VL 49 IS 6 BP 467 EP 468 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 493MT UT WOS:000172227800001 ER PT J AU Kao, CHK Sassaman, MB Szajek, LP Ma, Y Waki, A Eckelman, WC AF Kao, CHK Sassaman, MB Szajek, LP Ma, Y Waki, A Eckelman, WC TI The sequential syntheses of [Br-76]FBAU 3 ',5 '-dibenzoate and [Br-76]FBAU SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE bromine-76; thymidine; proliferation marker; PET; FBAU ID DNA-SYNTHESIS; PET; THYMIDINE; NUCLEOSIDES; TISSUES; I-123; F-18 AB Thymidine analogs labeled with positron emitting radionuclides are potential proliferation markers for positron emission tomography (PET). Bromine-76 (T-1/2 = 16.2 h) is our choice of radionuclide, because it allows for maximal DNA incorporation of the tracer. Following the literature descriptions, Br-76 was produced using the As-75 (He-3, 2n) Br-76 reaction. We then recovered Br-76 from the target in the form of [Br-76]NH4Br with a yield of 60 +/- 12% (n = 32). Peracetic acid was used as the oxidant for electrophilic bromodestannylation to prepare [Br-76]FBAU 3 ' ,5 ' -dibenzoate (71.2 +/- 12.1%, RCY) and a basic hydrolysis of the dibenzoate then yielded [Br-76]FBAU. The yield of the hydrolysis reaction was 53.1 +/- 9.2% when heated at 100 degreesC for 15 min or quantitative (decay corrected) when left at room temperature overnight. The sequential synthesis of [Br-76]FBAU 3 ' ,5 ' -dibenzoate and [Br-76]FBAU allowed us to perform a side-by-side comparison of their metabolic stabilities. While [Br-76]FBAU 3 ' ,5 ' -dibenzoate was hydrolyzed to [Br-76]FBAU within 10 minutes by hepatocyte at 37 degreesC, [Br-76]FBAU was stable and no [Br-76]Br- was released from either radiopharmaceutical. Both compounds are potential proliferation markers for PET. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 NIH, Positron Emiss Tomog Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Kao, CHK (reprint author), NIH, CC, PET, 10-1C495,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. EM CK132j@nih.gov NR 26 TC 9 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD NOV PY 2001 VL 44 IS 13 BP 889 EP 898 DI 10.1002/jlcr.515 PG 10 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 496ZQ UT WOS:000172428600002 ER PT J AU Mason, D Andre, P Bensussan, A Buckley, C Civin, C Clark, E de Haas, M Goyert, S Hadam, M Hart, D Horejsi, V Meuer, S Morrissey, J Schwartz-Albiez, R Shaw, S Simmons, D Uguccioni, M van der Schoot, E Vivier, E Zola, H AF Mason, D Andre, P Bensussan, A Buckley, C Civin, C Clark, E de Haas, M Goyert, S Hadam, M Hart, D Horejsi, V Meuer, S Morrissey, J Schwartz-Albiez, R Shaw, S Simmons, D Uguccioni, M van der Schoot, E Vivier, E Zola, H TI CD antigens 2001 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE HLDA workshops; leukocyte molecules ID HUMAN DENDRITIC CELLS; MONOCLONAL-ANTIBODY; MOLECULAR CHARACTERIZATION; SURFACE-MOLECULE; PERIPHERAL-BLOOD; RECEPTOR; MEMBER; CLONING; FAMILY; MACROPHAGES AB This paper reviews the Seventh Human Leucocyte Differentiation Antigen (HLDA7) workshop. Due to the limitations of "blind" antibody screening, which had been evident at the previous meeting in 1996, participants at HLDA7 adopted a more selective approach to the choice of antibodies by identifying new CD specificities. This resulted in the addition of more than 80 new CD specificities. Plans for the eighth and subsequent workshops are also previewed. C1 John Radcliffe Hosp, Dept Haematol, Oxford OX3 9DU, England. MRC, Ctr Immune Regulat, Div Immun & Infect, Birmingham, W Midlands, England. Celltech Ltd, R&D, Cambridge, England. CNRS, INSERM, Ctr Immunol, Marseille, France. INSERM, Creteil, France. Johns Hopkins Comprehens Canc Ctr, Baltimore, MD USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Netherlands Dept Expt Immunohematol, Cent Lab, Amsterdam, Netherlands. Cornell Univ, Coll Med, Lab Mol Hematol, Div Mol Med, Manhasset, NY 11030 USA. Med Hsch Hannover, Kinderklin, Hannover, Germany. Univ Heidelberg, Inst Immunol, Heidelberg, Germany. German Canc Res Ctr, Heidelberg, Germany. Mater Hosp, Mater Med Res Inst, S Brisbane, SA, Australia. Womens & Childrens Hosp, Child Hlth Res Inst, N Adelaide, SA, Australia. Acad Sci Czech Republ, Inst Mol Genet, Prague, Czech Republic. Univ Illinois, Coll Med, Urbana, IL 61801 USA. NIH, Bethesda, MD 20892 USA. Inst Res Biomed, Bellinzona, Switzerland. RP Mason, D (reprint author), John Radcliffe Hosp, Dept Haematol, Oxford OX3 9DU, England. RI Horejsi, Vaclav/G-3113-2014; Bensussan, Armand/E-5434-2017; OI Uguccioni, Mariagrazia/0000-0002-9570-7011 NR 33 TC 3 Z9 4 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2001 VL 70 IS 5 BP 685 EP 690 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 491ZM UT WOS:000172140500001 PM 11698486 ER PT J AU Rosenberg, HF Domachowske, JB AF Rosenberg, HF Domachowske, JB TI Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE pneumonia virus of mice; major basic protein ID CATIONIC PROTEIN; SYNCYTIAL VIRUS; PNEUMONIA VIRUS; AIRWAY HYPERREACTIVITY; INFLAMMATORY RESPONSE; ANTIVIRAL ACTIVITY; VIRAL-INFECTIONS; RAPID EVOLUTION; MICE; GENE AB Eosinophils remain among the most enigmatic of cells, as our appreciation of their detrimental activities-e.g., asthma and allergic disease-far outweighs our understanding of their beneficial effects. Among the major secretory effector proteins of eosinophils are the ribonucleases eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in primates and their orthologs, the eosinophil-associated ribonucleases (EARS) in rodents. The rapid diversification observed among these ribonucleases suggested that the ultimate target(s) might be similarly efficient at generating sequence diversity while maintaining an unalterable susceptibility to ribonucleolytic cleavage. This has prompted us to consider a role for these proteins and by extension, for eosinophils, in host defense against single-stranded RNA virus pathogens. We detail our studies of the antiviral activity of eosinophils and eosinophil ribonucleases against respiratory syncytial virus (RSV) in vitro and the related, natural rodent pathogen, pneumonia virus of mice (PVM), in vivo, and consider the possibility that antiviral host defense and the dysregulated responses leading to asthma represent opposing sides of an eosinophil-mediated double-edged sword. C1 NIAID, Eosinophil Biol Unit, Host Def Lab, NIH, Bethesda, MD 20892 USA. SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY USA. RP Rosenberg, HF (reprint author), NIAID, Eosinophil Biol Unit, Host Def Lab, NIH, Bldg 10,Room 11N104, Bethesda, MD 20892 USA. NR 63 TC 169 Z9 178 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2001 VL 70 IS 5 BP 691 EP 698 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 491ZM UT WOS:000172140500002 PM 11698487 ER PT J AU Dykstra, M Cherukuri, A Pierce, SK AF Dykstra, M Cherukuri, A Pierce, SK TI Rafts and synapses in the spatial organization of immune cell signaling receptors SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE multichain immune recognition receptors; Src family kinases; tyrosine phosphorylation; immune cell activation ID FC-EPSILON-RI; PROTEIN-TYROSINE KINASE; GPI-ANCHORED PROTEINS; LIPID RAFTS; MEMBRANE DOMAINS; ANTIGEN RECEPTOR; PLASMA-MEMBRANE; T-CELLS; IMMUNOLOGICAL SYNAPSE; TRANSMEMBRANE DOMAIN AB The multichain immune recognition receptors (MIRRs), including the T cell and B cell antigen receptors and the high affinity receptor for IgE, play an important role in immune cell signaling. The MIRRs have no inherent kinase activity, but rather associate with members of the Src-family kinases to initiate signaling. Although a great deal is understood about the biochemical cascades triggered by MIRRs, the mechanism by which signaling is initiated was not known. The evidence now indicates that the Src-family kinases are concentrated in cholesterol- and sphingolipid-rich membrane microdomains, termed lipid rafts, that exclude the MIRRs. Upon ligand-induced crosslinking the MIRRs translocate into rafts where they are phosphorylated. The MIRRs subsequently form highly ordered, polarized structures termed immunological synapses that provide for prolonged signaling. An understanding of the biochemical composition of rafts and synapses and the mechanisms by which these form should lend insight into the regulation of immune cell activation. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 200B,MSC 8180, Rockville, MD 20852 USA. NR 96 TC 43 Z9 47 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2001 VL 70 IS 5 BP 699 EP 707 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 491ZM UT WOS:000172140500003 PM 11698488 ER PT J AU Praetorius, HA Spring, KR AF Praetorius, HA Spring, KR TI Bending the MDCK cell primary cilium increases intracellular calcium SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE flow; calcium-induced calcium release; mechanical sensitivity; IP(3); gap junction; gadolinium ID LATERAL INTERCELLULAR SPACES; CANINE KIDNEY-CELLS; TUBULE; RAT; ACTIVATION; EPITHELIUM; SECRETION; SHEAR; ATP; K+ AB We tested the hypothesis that the primary cilium of renal epithelia is mechanically sensitive and serves as a flow sensor in MDCK cells using differential interference contrast and fluorescence microscopy. Bending the cilium, either by suction with a micropipette or by increasing the flow rate of perfusate, causes intracellular calcium to substantially increase as indicated by the fluorescent indicator, Fluo-4. This calcium signal is initiated by Ca(2+)-influx through mechanically sensitive channels that probably reside in the cilium or its base. The influx is followed by calcium release from IP(3)-sensitive stores. The calcium signal then spreads as a wave from the perturbed cell to its neighbors by diffusion of a second messenger through gap junctions. This spreading of the calcium wave points to flow sensing as a coordinated event within the tissue, rather than an isolated phenomenon in a single cell. Measurement of the membrane potential difference by microelectrode during perfusate flow reveals a profound hyperpolarization during the period of elevated intracellular calcium. We conclude that the primary cilium in MDCK cells is mechanically sensitive and responds to flow by greatly increasing intracellular calcium. C1 NTH, NHLBI, LKEM, Bethesda, MD 20892 USA. RP Praetorius, HA (reprint author), NTH, NHLBI, LKEM, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM praetorh@nhlbi.nih.gov NR 29 TC 491 Z9 508 U1 1 U2 23 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD NOV 1 PY 2001 VL 184 IS 1 BP 71 EP 79 DI 10.1007/s00232-001-0075-4 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 488UK UT WOS:000171954100008 PM 11687880 ER PT J AU Xavier, JB Schnell, A Wuertz, S Palmer, R White, DC Almeida, JS AF Xavier, JB Schnell, A Wuertz, S Palmer, R White, DC Almeida, JS TI Objective threshold selection procedure (OTS) for segmentation of scanning laser confocal microscope images SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE objective threshold selection; confocal laser scanning microscopy; robust automatic threshold selection ID BIOFILMS; COMMUNITY; GROWTH AB The determination of volumes and interface areas from confocal laser scanning microscopy (CLSM) images requires the identification of component objects by segmentation. An automated method for the determination of segmentation thresholds for CLSM imaging of biofilms was developed. The procedure, named objective threshold selection (OTS), is a three-dimensional development of the approach introduced by the popular robust automatic threshold selection (RATS) method. OTS is based on the statistical properties of local gray-values and gradients in the image, By characterizing the dependence between a volumetric feature and the intensity threshold used for image segmentation, the former can be determined with an arbitrary confidence level, with no need for user intervention. The identification of an objective segmentation procedure renders the possibility for the full automation of volume and interfacial area measurement. Images from two distinct biofilm systems, acquired using different experimental techniques and instrumental setups were segmented by OTS to determine biofilm volume and interfacial area. The reliability of measurements for each case was analyzed to identify optimal procedure for image acquisition. The automated OTS method was shown to reproduce values obtained manually by an experienced operator. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Oak Ridge Natl Lab, Div Environm Sci, Oak Ridge, TN 37831 USA. Univ Tennessee, Ctr Environm Biotechnol, Knoxville, TN 37932 USA. Natl Inst Dent Craniofacial Res, NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. Tech Univ Munich, Inst Water Qual Control & Waste Management, D-85748 Garching, Germany. Univ Nova Lisboa, Inst Tecnol Quim & Biol, P-2780 Oeiras, Portugal. RP Almeida, JS (reprint author), Med Univ S Carolina, Dept Biometry & Epidemiol, 135 Rutledge Ave,POB 250551, Charleston, SC 29425 USA. NR 23 TC 35 Z9 36 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD NOV PY 2001 VL 47 IS 2 BP 169 EP 180 DI 10.1016/S0167-7012(01)00298-6 PG 12 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 481GB UT WOS:000171510600004 PM 11576681 ER PT J AU Lappin, S Cahlik, J Gold, B AF Lappin, S Cahlik, J Gold, B TI Robot printing of reverse dot blot arrays for human mutation detection SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Clinical-Chemistry CY AUG 02-06, 1998 CL CHICAGO, ILLINOIS SP Amer Assoc Clin Chem ID POLYMERASE CHAIN-REACTION; BETA-THALASSEMIA MUTATIONS; CYSTIC-FIBROSIS MUTATIONS; DNA; HYBRIDIZATION; GENE AB We report on a generally useful, partially automated, human mutation detection method based upon printing moderate density oligonucleotide arrays using a biorobot on activated nylon membranes. The Beckman Biomek 2000 was adapted to this task through fabrication of aluminum membrane filter holders and the development of an addressable Tool Command Language (Tcl) program, which can be invoked through BioScript. During program execution, a robot arm is moved along the x, y, and z axes to expel liquid, without dripping, from disposable barrier pipette tips and then to touch the drops on preactivated membranes. Printed arrays consist of alternating rows of oligonucleotides containing normal and mutant sequences. Hybridization of biotin labeled polymerase chain reaction products derived from human patient genomic DNA samples are visualized using chemiluminescent or chromogenic indicators. This technique allows unequivocal genotyping of 32 mutations at the beta -thalassemia locus (11p15.5) and of 34 mutations and one polymorphism at the cystic fibrosis transconductance membrane regulator locus (7p35). C1 Quest Diagnost, Van Nuys, CA USA. Beckman Coulter, Fullerton, CA USA. RP Gold, B (reprint author), Natl Canc Inst, Lab Genomic Divers, Human Genet Sect, Frederick, MD 21702 USA. FU NCI NIH HHS [U24 CA092782, R24 CA092782] NR 21 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2001 VL 3 IS 4 BP 178 EP 188 DI 10.1016/S1525-1578(10)60670-8 PG 11 WC Pathology SC Pathology GA 489JX UT WOS:000171989200008 PM 11687602 ER PT J AU Rashid, MA Gustafson, KR Boyd, MR AF Rashid, MA Gustafson, KR Boyd, MR TI New cytotoxic N-methylated beta-carboline alkaloids from the marine ascidian Eudistoma gilboverde SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID OLIVACEUM; GLAUCUS AB Bioassay-guided fractionation of an extract of the marine ascidian Eudistoma gilboverde provided three new beta -carboline alkaloids identified as 2-methyleudistomin D (1), 2-methyleudistomin J (2), and 14-methyleudistomidin C (3). Six known metabolites, eudistomins C, D (4), E, J (5), K, and L, were also isolated and characterized. The structures of the new metabolites were elucidated by spectroscopic analyses and by comparison of their spectral data with related literature values. Of the three now compounds, 14-methyleudistomidin C (3) exhibited the most potent cytotoxic activity with IC50's of < 1.0 mug/mL against four different human tumor cell lines. C1 NCI, Ctr Canc Res, Mol Targets Drug Discovery Program, Frederick, MD 21702 USA. NCI, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Ctr Canc Res, Mol Targets Drug Discovery Program, Bldg 1052,Room 121, Frederick, MD 21702 USA. EM boyd@dtpax2.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 24 TC 41 Z9 44 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD NOV PY 2001 VL 64 IS 11 BP 1454 EP 1456 DI 10.1021/np010214+ PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 498EE UT WOS:000172496200015 PM 11720532 ER PT J AU Meragelman, KM McKee, TC Boyd, MR AF Meragelman, KM McKee, TC Boyd, MR TI 10-demethoxystegane, a new lignan from Steganotaenia araliacea SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID BISBENZOCYCLOOCTADIENOLACTONIC LIGNAN; HOCHST; NEOISOSTEGANE; LACTONE AB A new dibenzocyclooctadiene lactone lignan, 10-demethoxystegane (1), together with the known compounds steganone (2) and prestegane B (3), have been isolated from the organic extract of Steganotaenia araliaeca (Apiaceae). Steganone (2) showed antiproliferative activity against an ovarian cancer cell line (OVCAR-3). C1 NCI, Canc Res Ctr, Mol Targets Drug Discovery Program, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Canc Res Ctr, Mol Targets Drug Discovery Program, Frederick, MD 21702 USA. EM boyd@dtpax2.ncifcrf.gov NR 17 TC 9 Z9 10 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD NOV PY 2001 VL 64 IS 11 BP 1480 EP 1482 DI 10.1021/np010248h PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 498EE UT WOS:000172496200024 PM 11720541 ER PT J AU Xiong, LW Raymond, LD Hayes, SF Raymond, GJ Caughey, B AF Xiong, LW Raymond, LD Hayes, SF Raymond, GJ Caughey, B TI Conformational change, aggregation and fibril formation induced by detergent treatments of cellular prion protein SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE circular dichroism; detergents; fibrils; fluorescence; infrared; prion protein ID SCRAPIE PRION; INFRARED-SPECTROSCOPY; SYNTHETIC PEPTIDES; PRP 27-30; RESISTANT; CONVERSION; FORM; POLYPEPTIDE; KINETICS; BRAIN AB The conversion of protease-sensitive prion protein (PrP-sen) to a high beta -sheet, protease-resistant and often fibrillar form (PrP-res) is a central event in transmissible spongiform encephalopathies (TSE) or prion diseases. This conversion can be induced by PrP-res itself in cell-free conversion reactions. The detergent sodium N-lauroyl sarkosinate (sarkosyl) is a detergent that is widely used in PrP-res purifications and is known to stimulate the PrP-res-induced conversion reaction. Here we report effects of sarkosyl and other detergents on recombinant hamster PrP-sen purified from mammalian cells under oxidizing conditions that maintain the single native disulfide bond. Low concentrations of sarkosyl (0.001-0.1%) induced aggregation of PrP-sen molecules, increased light scattering, altered fluorescence excitation and emission spectra, and enhanced the proportion of beta -sheet secondary structure according to circular dichroism and infrared spectroscopies. An enhancement of beta -sheet content was also seen with 0.001% sodium dodecyl sulfate (SIDS) but not several other types of detergents. Electron microscopy revealed that sarkosyl induced the formation of both amorphous and fibrillar aggregates. The fibrils appeared to be constructed from spherical bead-like protofibrils. Neither TSE infectivity nor the characteristic partial proteinase K resistance of PrP-res was detected in the sarkosyl-induced PrP aggregates. We conclude that certain anionic detergents can disrupt the conformation of PrP-sen and induce high beta -sheet aggregates that are distinct from scrapie-associated PrP-res in terms of protease-resistance, infrared spectrum and infectivity. These results reinforce the idea that not all high-beta aggregates of PrP are equivalent to the pathologic form, PrP-res. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Microscopy Branch, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 46 TC 45 Z9 47 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2001 VL 79 IS 3 BP 669 EP 678 DI 10.1046/j.1471-4159.2001.00606.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 488UM UT WOS:000171954300021 PM 11701770 ER PT J AU Levin-Allerhand, J McEwen, BS Lominska, CE Lubahn, DB Korach, KS Smith, JD AF Levin-Allerhand, J McEwen, BS Lominska, CE Lubahn, DB Korach, KS Smith, JD TI Brain region-specific up-regulation of mouse apolipoprotein E by pharmacological estrogen treatments SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apolipoprotein E; 17 alpha-estradiol; 17 beta-estradiol; estrogen receptor alpha knockout ID FIBRILLARY ACIDIC PROTEIN; HYPOTHALAMIC ARCUATE NUCLEUS; DENDRITIC SPINE DENSITY; CENTRAL-NERVOUS-SYSTEM; BETA MESSENGER-RNA; E GENE-EXPRESSION; RECEPTOR-BETA; ALZHEIMERS-DISEASE; RAT-BRAIN; IN-VITRO AB Cerebral apolipoprotein E (apoE) has been implicated in neuronal protection and repair. Dub to the variable levels and types of estrogen receptors within different brain regions, the effect of estrogen on apoE and the mechanism of this effect may vary within different regions. Ovariectomized female C57BL/6 mice were treated with pharmacological levels of 17 beta -estradiol or placebo for 5 days, resulting in supraphysiological plasma levels of estradiol in the treated mice. ApoE and glial fibrillary acidic protein (GFAP) levels were measured in the cortex, hippocampus and diencephalon. 17 beta -Estradiol up-regulated apoE but not GFAP in the cortex and diencephalon, whereas in the hippocampus, GFAP and apoE were equally up-regulated. Treatment of estrogen receptor (ER) knockout mice with 17 beta -estradiol or treatment of C57BL/6 mice with 17 alpha -estradiol, a poor estrogen receptor agonist, specifically induced apoE in the cortex, but not in the diencephalon. These results indicate that 17 beta -estradiol effects on apoE are either directly or indirectly mediated by ER alpha in the diencephalon, while the effects in the cortex may be mediated by a non-classical mechanism or by ER beta. Measurement of mRNA levels in estrogen versus placebo-treated wildtype mice indicated that the effect of 17 beta -estradiol on apoE was not associated with changes in apoE mRNA levels. C1 Rockefeller Univ, Biochem Genet & Metab Lab, New York, NY 10021 USA. Univ Missouri, Dept Biochem, Columbia, MO USA. Univ Missouri, Dept Child Hlth, Columbia, MO 65201 USA. NIEHS, Lab Reprod Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Smith, JD (reprint author), Rockefeller Univ, Biochem Genet & Metab Lab, 1230 York Ave, New York, NY 10021 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 58 TC 41 Z9 42 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2001 VL 79 IS 4 BP 796 EP 803 DI 10.1046/j.1471-4159.2001.00627.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 495AG UT WOS:000172317600009 PM 11723172 ER PT J AU Umeno, MM Goldberg, ME AF Umeno, MM Goldberg, ME TI Spatial processing in the monkey frontal eye field. II. Memory responses SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATERAL INTRAPARIETAL AREA; SUPERIOR COLLICULUS; PARIETAL CORTEX; NEURONAL-ACTIVITY; SINGLE NEURONS; VISUAL SPACE; REPRESENTATION; MOVEMENTS; MAINTENANCE; SALIENCE AB Monkeys and humans can easily make accurate saccades to stimuli that appear and disappear before an intervening saccade to a different location. We used the flashed-stimulus task to study the memory processes that enable this behavior, and we found two different kinds of memory responses under these conditions. In the short-term spatial memory response, the monkey fixated, a stimulus appeared for 50 ms outside the neuron's receptive field, and from 200 to 1,000 ms later the monkey made a saccade that brought the receptive field onto the spatial location of the vanished stimulus. Twenty-eight of 48 visuomovement cells and 21/32 visual cells responded significantly under these circumstances even though they did not discharge when the monkey made the same saccade without the stimulus present or when the stimulus appeared and the monkey did not make a saccade that brought its spatial location into the receptive field. Response latencies ranged from 48 ms before the beginning of the saccade (predictive responses) to 272 ms after the beginning of the saccade. After the monkey made a series of 16 saccades that brought a stimulus into the receptive field, 21 neurons demonstrated a longer term, intertrial memory response: they discharged even on trials in which no stimulus appeared at all. This intertrial memory response was usually much weaker than the within-trial memory response, and it often lasted for over 20 trials. We suggest that the frontal eye field maintains a spatially accurate representation of the visual world that is not dependent on constant or continuous visual stimulation, and can last for several minutes. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. American Univ, Dept Phys, Washington, DC 20016 USA. Georgetown Univ, Sch Med, Dept Neurol, Washington, DC 20007 USA. RP Goldberg, ME (reprint author), NEI, Sensorimotor Res Lab, Bldg 10,Rm 2A50, Bethesda, MD 20892 USA. NR 26 TC 91 Z9 91 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2001 VL 86 IS 5 BP 2344 EP 2352 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 489VH UT WOS:000172012800020 PM 11698524 ER PT J AU Eberwine, J Kacharmina, JE Andrews, C Miyashiro, K McIntosh, T Becker, K Barrett, T Hinkle, D Dent, G Marciano, P AF Eberwine, J Kacharmina, JE Andrews, C Miyashiro, K McIntosh, T Becker, K Barrett, T Hinkle, D Dent, G Marciano, P TI mRNA expression analysis of tissue sections and single cells SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LOCAL PROTEIN-SYNTHESIS; GENE-EXPRESSION; NEURONS; HYBRIDIZATION; MACHINERY; DENDRITES; PROFILES; AMYGDALA; ARRAYS; BRAIN C1 Univ Penn, Med Ctr, Dept Pharmacol & Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Neurosurg, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. NIA, DNA Array Unit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Eberwine, J (reprint author), Univ Penn, Med Ctr, Dept Pharmacol, 36th & Hamilton Walk, Philadelphia, PA 19104 USA. RI Eberwine, James/B-2247-2010; OI Becker, Kevin/0000-0002-6794-6656 NR 26 TC 59 Z9 64 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2001 VL 21 IS 21 BP 8310 EP 8314 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 482ZL UT WOS:000171608600007 PM 11606616 ER PT J AU Diamond, JS AF Diamond, JS TI Neuronal glutamate transporters limit activation of NMDA receptors by neurotransmitter spillover on CA1 pyramidal cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE spillover; glutamate transporters; diffusion; Monte Carlo simulation; hippocampus; NMDA receptor ID SYNAPTICALLY RELEASED GLUTAMATE; CEREBELLAR GRANULE CELLS; BERGMANN GLIAL-CELLS; MOSSY FIBER SYNAPSES; TIME-COURSE; EXTRASYNAPTIC GLUTAMATE; RAT HIPPOCAMPUS; SILENT SYNAPSES; DENDRITIC MORPHOLOGY; PARALLEL FIBER AB Glutamate released at synapses in the CA1 region of the hippocampus escapes the synaptic cleft and activates extrasynaptic targets; it also may "spill over" into neighboring synapses and activate receptors there. Glutamate transporters in glial membranes restrict extrasynaptic diffusion, but it is unclear whether neuronal glutamate transporters also limit transmitter diffusion and receptor activation by spillover. I examined the effects of a low-affinity competitive NMDA receptor antagonist on EPSCs in acute hippocampal slices to distinguish receptors activated within active synapses from those activated by spillover. Glutamate spillover is observed between Schaffer collateral fiber synapses onto CA1 pyramidal cells only when transporters in the postsynaptic neuron are inhibited. Because glutamate transporters operate most effectively at negative membrane potentials, these results suggest that activation of NMDA receptors by spillover may depend on postsynaptic activity. C1 NINCDS, Synapt Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Diamond, JS (reprint author), NINCDS, Synapt Physiol Unit, NIH, Bldg 36,Room 2C09,36 Convent Dr, Bethesda, MD 20892 USA. RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 NR 64 TC 177 Z9 179 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2001 VL 21 IS 21 BP 8328 EP 8338 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 482ZL UT WOS:000171608600011 PM 11606620 ER PT J AU Singer, JH Mirotznik, RR Feller, MB AF Singer, JH Mirotznik, RR Feller, MB TI Potentiation of L-type calcium channels reveals nonsynaptic mechanisms that correlate spontaneous activity in the developing mammalian retina SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retinal waves; development; visual system; calcium imaging; network; gap junctions ID GAP JUNCTIONAL COMMUNICATION; DEVELOPING NEURAL CIRCUITS; VISUAL-SYSTEM DEVELOPMENT; GANGLION-CELLS; AMACRINE CELLS; CONNEXIN EXPRESSION; GLYCYRRHETINIC ACID; GLUTAMATE RELEASE; BURSTING ACTIVITY; INFERIOR OLIVE AB Although correlated neural activity is a hallmark of many regions of the developing nervous system, the neural events underlying its propagation remain largely unknown. In the developing vertebrate retina, waves of spontaneous, correlated neural activity sweep across the ganglion cell layer. Here, we demonstrate that L-type Ca2+ channel agonists induce large, frequent, rapidly propagating waves of neural activity in the developing retina. In contrast to retinal waves that have been described previously, these L-type Ca2+ channel agonist-potentiated waves propagate independent of fast synaptic transmission. Bath application of nicotinic acetylcholine, AMPA, NMDA, glycine, and GABAA receptor antagonists does not alter the velocity, frequency, or size of the potentiated waves. Additionally, these antagonists do not alter the frequency or magnitude of spontaneous depolarizations that are recorded in individual retinal ganglion cells. Like normal retinal waves, however, the area over which the potentiated waves propagate is reduced dramatically by 18 alpha -glycyrrhetinic acid, a blocker of gap junctions. Additionally, like normal retinal waves, L-type Ca2+ channel agonist-potentiated waves are abolished by adenosine deaminase, which degrades extracellular adenosine, and by aminophylline, a general adenosine receptor antagonist, indicating that they are dependent on adenosine-mediated signaling. Our study indicates that although the precise spatiotemporal properties of retinal waves are shaped by local synaptic inputs, activity may be propagated through the developing mammalian retina by nonsynaptic pathways. C1 NINCDS, Synapse Format & Funct Unit, NIH, Bethesda, MD 20892 USA. RP Singer, JH (reprint author), NINCDS, Synapse Format & Funct Unit, NIH, MSC-4066,Bldg 36,Room 2C09, Bethesda, MD 20892 USA. NR 64 TC 48 Z9 48 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2001 VL 21 IS 21 BP 8514 EP 8522 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 482ZL UT WOS:000171608600031 PM 11606640 ER PT J AU Piper, DR Mujtaba, T Keyoung, H Roy, NS Goldman, SA Rao, MS Lucero, MT AF Piper, DR Mujtaba, T Keyoung, H Roy, NS Goldman, SA Rao, MS Lucero, MT TI Identification and characterization of neuronal precursors and their progeny from human fetal tissue SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE stem cells; differentiation; electrophysiology ID CENTRAL-NERVOUS-SYSTEM; NEUROEPITHELIAL STEM-CELLS; EMBRYONIC HUMAN CNS; ADULT HUMAN BRAIN; HUMAN SPINAL-CORD; IN-VITRO; MONOCLONAL-ANTIBODIES; NEURAL PRECURSORS; WHITE-MATTER; MULTIPOTENT AB We have examined primary human neuronal precursors (HNPs) from 18-22-week-old fetuses. We showed that E-NCAM/MAP2/beta -III tubulin-immunoreactive neuronal precursors divide in vitro and could be induced to differentiate into mature neurons in 2 weeks. HNPs did not express nestin and differentiated slowly compared to rodent neuronal restricted precursors (NRPs, 5 days). Immunocytochemical and physiological analyses showed that HNPs could generate a heterogeneous population of neurons that expressed neurofilament-associated protein and various neurotransmitters, neurotransmitter synthesizing enzymes, voltage-gated ion channels, and ligand-gated neurotransmitter receptors and could fire action potentials. Undifferentiated and differentiated HNPs did not coexpress glial markers. Only a subset of cells that expressed GFP under the control of the T alpha1 tubulin promoter was E-NCAM/beta -III tubulin-immunoreactive, indicating nonexclusive overlap between these two HNP cell populations. Overall, HNPs resemble NRPs isolated from rodent tissue and appear to be a neuronal precursor population. (C) 2001 Wiley-Liss, Inc. C1 Univ Utah, Sch Med, Dept Physiol, Salt Lake City, UT 84108 USA. NIA, NIUS, GRC, Baltimore, MD 21224 USA. Cornell Univ, Coll Med, Dept Neurol & Neurosci, New York, NY USA. RP Univ Utah, Sch Med, Dept Physiol, 410 Chipeta Way,Room 155, Salt Lake City, UT 84108 USA. EM mary.lucero@m.cc.utah.edu FU NIDCD NIH HHS [DC02994, R01 DC002994, R01 DC002994-05S1] NR 39 TC 55 Z9 56 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 2001 VL 66 IS 3 BP 356 EP 368 DI 10.1002/jnr.1228 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 488LH UT WOS:000171936300006 PM 11746353 ER PT J AU Jahnke, GD Brunssen, S Maier, WE Harry, G AF Jahnke, GD Brunssen, S Maier, WE Harry, G TI Neurotoxicant-induced elevation of adrenomedullin expression in hippocampus and glia cultures SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE adrenomedullin; astrocytes; trimethyltin; TNF alpha; IL-1 alpha; GFAP ID TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; GENE-RELATED PEPTIDE; SMOOTH-MUSCLE CELLS; FACTOR-ALPHA; BRAIN; NEUROBLASTOMA; TRIMETHYLTIN; ASTROCYTES; INTERLEUKIN-1 AB Adrenomedullin (AM), a vasoactive peptide first isolated from pheochromocytoma, has been reported to be present in neurons in the central nervous system and in tumors of neural and glial origin. In this study, we investigated AM expression both in the hippocampus and in glial cell cultures using a chemical-induced model of injury. An acute intraperitoneal injection of the organometal trimethyltin (TMT) results in neurodegeneration of the hippocampal CA3-4 pyramidal cell layer. Within 4 days of injection, sparse, punctate staining for AM and lectin was evident in the CA3-4 region; by 10 days, a minimal level of CA3-4 neuronal degeneration was evident, with an increase in glial fibrillary acidic protein (GFAP)-positive astrocytes throughout the hippocampus. Degeneration progressed in severity until 30 days post-TMT, with distinct positive immunoreactivity for AM in the CA4 region. mRNA levels for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, GFAP, and AM in the hippocampus were increased over control levels within 4 days following TMT. In cultured glial cells, a 6 hr exposure to TMT (10 muM) produced a morphological response of the cells and increased immunoreactivity for vimentin, GFAP, and AM. mRNA levels for TNF alpha, IL-1 alpha, GFAP, vimentin, and AM were elevated within 3-6 hr of exposure. In culture, neutralizing antibodies to IL-1 alpha and TNF alpha were effective in inhibiting the TMT-induced elevation of AM mRNA. These data suggest an interaction between the proinflammatory cytokines and glia response in the regulation of AM in response to injury. Published 2001 Wiley-Liss, Inc. C1 NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Jahnke, GD (reprint author), NIEHS, Toxicol Lab, POB 12233,MD EC-32, Res Triangle Pk, NC 27709 USA. NR 36 TC 18 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 2001 VL 66 IS 3 BP 464 EP 474 DI 10.1002/jnr.1237 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 488LH UT WOS:000171936300017 PM 11746364 ER PT J AU Richardson, MA AF Richardson, MA TI Biopharmacologic and herbal therapies for cancer: Research update from NCCAM SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 11th Annual Research Conference on Diet, Nutrition and Cancer CY JUL 16-17, 2001 CL WASHINGTON, D.C. SP Amer Inst Canc Res DE alternative; complementary; cancer; research; NCCAM ID ALTERNATIVE MEDICINE USE; BREAST-CANCER; COMPLEMENTARY/ALTERNATIVE MEDICINE; ONCOLOGY; WOMEN AB During the past decade, use of complementary and alternative medicine (CAM) by the American public increased from 34% in 1990 to 42% in 1995 with related out-of-pocket expenditures estimated at $27 billion. Among cancer patients, use of CAM ranges between 30 and 75% worldwide and includes dietary approaches, herbals and other biologically based treatments such as melatonin, mushrooms, shark cartilage and high dose vitamins and minerals. Concerns about herb-nutrient-drug interactions and product quality and standardization emphasize the need for rigorous research. In 1998, Congress mandated the creation of the National Center for Complementary and Alternative Medicine (NCCAM) to conduct and support such research of CAM therapies. The NCCAM portfolio for oncology is rapidly growing. As of July 2001, 26 projects are underway, two specialized centers are funded for cancer research and four botanical centers are cofunded with the Office of Dietary Supplements. Investigations are targeting herbals and complex herbal formulas; single dietary supplements and complex dietary regimens; biological agents; and mind-body, body-based and frontier approaches. Of these, biopharmacologic and herbal therapies are a major focus of research. The NCCAM portfolio illustrates how research of CAM, particularly studies of biopharmacologic and herbal approaches for cancer, is developing systematically and rigorously. C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Richardson, MA (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NR 15 TC 17 Z9 18 U1 0 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2001 VL 131 IS 11 SU S BP 3037S EP 3040S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 496AH UT WOS:000172372200004 PM 11694644 ER PT J AU Hursting, SD Perkins, SN Phang, JM Barrett, JC AF Hursting, SD Perkins, SN Phang, JM Barrett, JC TI Diet and cancer prevention studies in p53-deficient mice SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 11th Annual Research Conference on Diet, Nutrition and Cancer CY JUL 16-17, 2001 CL WASHINGTON, D.C. SP Amer Inst Canc Res DE nutrition; chemoprevention; transgenic animals; calorie restriction; insulin-like growth factor-1; leptin ID CALORIE RESTRICTION; SPONTANEOUS TUMORIGENESIS; CELL-PROLIFERATION; TRANSGENIC MICE; GROWTH; LEPTIN; P53; PROGRESSION; INHIBITION; APOPTOSIS AB Progress in mechanism-based cancer prevention research may be facilitated by the use of animal models displaying specific genetic susceptibilities for cancer such as mice deficient in the p53 tumor suppressor gene, the most frequently altered gene in human cancer. We observed in p53-knockout (p53-/-) mice that calorie restriction (CR; 60% of the control group's intake of carbohydrate energy) increased the latency of spontaneous tumor development (mostly lymphomas) similar to 75%, decreased serum insulin-like growth factor (IGF)-1 and leptin levels, significantly slowed thymocyte cell cycle traverse and induced apoptosis in immature thymocytes. In heterozygous p53-deficient (p53+/-) mice, CR and 1 d/wk of food deprivation each significantly delayed spontaneous tumor development (a mix of lymphomas, sarcomas and epithelial tumors) and decreased serum IGF-1 and leptin levels even when begun late in life. We have also developed a rapid and relevant p53+/- mouse mammary tumor model by crossing p53-deficient mice with MMTV-Wnt-1 transgenic mice, and found that CR and 1 d/wk food deprivation significantly increased mammary tumor latency (greater than twofold) and reduced the mean serum IGF-1 and leptin levels to < 50% of that of control mice (P < 0.0001). In addition, fluasterone, fenretinide and soy each delayed tumor development but had little effect on IGF-1 or leptin levels. We have capitalized on the susceptibility of p53+/- mice to chronic, low dose, aromatic amine-induced bladder carcinogenesis to develop a useful model for evaluating bladder cancer prevention approaches such as cyclooxygenase-2 inhibition. As demonstrated by these examples, mice with specific (and human-like) genetic susceptibilities for cancer provide powerful new tools for testing and characterizing interventions that may inhibit the process of carcinogenesis in humans. C1 NCI, Bethesda, MD 20892 USA. RP Hursting, SD (reprint author), NCI, Bethesda, MD 20892 USA. NR 26 TC 42 Z9 42 U1 1 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2001 VL 131 IS 11 SU S BP 3092S EP 3094S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 496AH UT WOS:000172372200014 PM 11694654 ER EF