FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kimbro, KS Migliaccio, S Korach, KS AF Kimbro, KS Migliaccio, S Korach, KS TI Analysis of bone from mice with the disrupted estrogen receptor gene. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIEHS,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP 121 EP 121 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500121 ER PT J AU Schwartzberg, P Xing, L Lowell, CA Lee, E Garrett, L Reddy, S Roodman, GD Boyce, B Varmus, HE AF Schwartzberg, P Xing, L Lowell, CA Lee, E Garrett, L Reddy, S Roodman, GD Boyce, B Varmus, HE TI Complementation of osteopetrosis in SRC-/-mice does not require SRC kinase activity. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIH, BETHESDA, MD 20892 USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP 162 EP 162 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500163 ER PT J AU Xing, L Schwartzberg, P Reddy, SV Roodman, GD Mundy, GR Varmus, HE Boyce, BF AF Xing, L Schwartzberg, P Reddy, SV Roodman, GD Mundy, GR Varmus, HE Boyce, BF TI Induction of osteoclast apoptosis in transgenic mice by a truncated Src protein SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP 182 EP 182 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500183 ER PT J AU Ding, CL Usdin, TB Labuda, M Levine, MA AF Ding, CL Usdin, TB Labuda, M Levine, MA TI Molecular genetic analysis of pseudohypoparathyroidism type 1B: Exclusion of the genes encoding the type 1 and type 2 PTH receptors. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,DEPT PSYCHIAT,BALTIMORE,MD 21205. NIMH,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M483 EP M483 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500828 ER PT J AU Fisher, LW Young, MF Whitson, M Whitson, SW AF Fisher, LW Young, MF Whitson, M Whitson, SW TI Cortisol and PTH affect matrix mineralization and mRNA levels of osteocalcin, bone sialoprotein and osteopontin. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. SO ILLINOIS UNIV,ALTON,IL 62002. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M445 EP M445 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500791 ER PT J AU Jayme, JJ Harman, SM OConnor, KG Tobin, JD Roy, TA StClair, C Gusenoff, J Blackman, MR AF Jayme, JJ Harman, SM OConnor, KG Tobin, JD Roy, TA StClair, C Gusenoff, J Blackman, MR TI The inverse relationship between cortisol secretion and bone mineral density in healthy elderly persons is related to gender and body composition. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M586 EP M586 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500933 ER PT J AU Migliaccio, S Toverud, S Teti, A Jefferson, WN Korach, KS Taranta, A Newbold, RR AF Migliaccio, S Toverud, S Teti, A Jefferson, WN Korach, KS Taranta, A Newbold, RR TI Transient alterations of estrogen levels during development affect osteoclastic cells in adulthood SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV ROMA LA SAPIENZA,HISTOL EMBRIOL GEN INST,I-00161 ROME,ITALY. UNIV LAQUILA,DEPT MED SPER,IDI,I-76100 ROME,ITALY. NIEHS,LRDT,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH DENT,CHAPEL HILL,NC 27514. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M407 EP M407 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500752 ER PT J AU Takemura, M Bergwitz, C Usdin, TB Juppner, H Segre, GV AF Takemura, M Bergwitz, C Usdin, TB Juppner, H Segre, GV TI Specific determinants in the first and second transmembrane helices of the PTH/PTHrP receptor are necessary for stimulating phospholipase C, but not for stimulating adenylyl cyclase SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M499 EP M499 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500844 ER PT J AU Tanaka, H Liang, CT AF Tanaka, H Liang, CT TI Basic fibroblast growth factor regulates proliferation and differentiation in rat bone marrow stromal cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M315 EP M315 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500660 ER PT J AU Wakasaka, A Liang, CT AF Wakasaka, A Liang, CT TI Effect of minocycline on bone turnover in ovariectomized old rats. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M666 EP M666 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501013 ER PT J AU Young, MF Kutznesov, SA Robey, PG OConnell, B AF Young, MF Kutznesov, SA Robey, PG OConnell, B TI Lysine conjugated adenovirus-DNA complexes: A novel method of gene transfer into normal human cells derived from the skeleton SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP M363 EP M363 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500708 ER PT J AU Bellahcene, A Antoine, N Clausse, N Tagliabue, E Fisher, LW Kerr, JM Jarez, P Castronovo, V AF Bellahcene, A Antoine, N Clausse, N Tagliabue, E Fisher, LW Kerr, JM Jarez, P Castronovo, V TI Detection of bone sialoprotein in human breast cancer tissue and cell lines at both protein and messenger ribonucleic acid levels. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 METASTASIS RES LAB,LIEGE,BELGIUM. IST NAZL TUMORI,I-20133 MILAN,ITALY. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. PATHOL LAB,BARCELONA,SPAIN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP P224 EP P224 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500208 ER PT J AU Kremer, R Papavasiliou, V Rabbani, SA Rhim, JS Goltzman, D AF Kremer, R Papavasiliou, V Rabbani, SA Rhim, JS Goltzman, D TI Reversal of hypercalcemia with the vitamin D analog EB1089 in a human model of squamous cancer. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 ROYAL VICTORIA HOSP,DEPT MED,MONTREAL,PQ H3A 1A1,CANADA. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP P289 EP P289 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500273 ER PT J AU Riminucci, M Shenker, A Spiegel, A Bianco, P Robey, PG AF Riminucci, M Shenker, A Spiegel, A Bianco, P Robey, PG TI Cell retraction and abnormal expression of adhesive and anti-adhesive proteins in bone lesions of McCune-Albright Syndrome (MAS). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NIDDK,NIH,BETHESDA,MD 20892. UNIV LAQUILA,I-67100 LAQUILA,ITALY. UNIV ROMA LA SAPIENZA,ROME,ITALY. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP P227 EP P227 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500210 ER PT J AU Cohen, IR Gajko, A Marini, JC AF Cohen, IR Gajko, A Marini, JC TI Expression and regulation of type I collagen and other matrix components in Osteogenesis Imperfecta osteoblasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NICHHD,HDB,SECT CONNECT TISSUE DISORDERS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP S644 EP S644 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500623 ER PT J AU Czerwiec, FS Cutler, GB AF Czerwiec, FS Cutler, GB TI Somatostatin as a modulator of osteoblast differentiation: Implications for the therapy of fibrous dysplasia of bone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP S640 EP S640 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500619 ER PT J AU Langlois, JA Maagi, S AF Langlois, JA Maagi, S TI Weight and physical disability as risk factors for hip fracture in older men. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. UNIV PADUA,CNR,PROGRAM AGING,INST HYG,I-35128 PADUA,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP S571 EP S571 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500551 ER PT J AU LethbridgeCejku, M Hochberg, MC Roy, TA Plato, CC Tobin, JD AF LethbridgeCejku, M Hochberg, MC Roy, TA Plato, CC Tobin, JD TI Smoking is associated with lower femoral neck bone mineral density in men but not in women: Data from the Baltimore longitudinal study of aging. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV MARYLAND,BALTIMORE,MD 21224. NIA,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP S534 EP S534 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49500513 ER PT J AU Barsony, J Gould, DL McKoy, W Holick, MF Chen, TC Htun, H Hager, GL AF Barsony, J Gould, DL McKoy, W Holick, MF Chen, TC Htun, H Hager, GL TI Rapid actions of steroids are independent from receptors on the plasma membrane but related to translocation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,BOSTON,MA 02118. NIDDK,LCBB,BETHESDA,MD 20892. NCI,MOL VIROL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP T532 EP T532 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501349 ER PT J AU Benayahu, D Fisher, LW Stubbs, JT Robey, PG AF Benayahu, D Fisher, LW Stubbs, JT Robey, PG TI A novel protein expressed by marrow stromal cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BONE RES BRANCH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP T370 EP T370 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501188 ER PT J AU Delany, AM Young, MF Canalis, E AF Delany, AM Young, MF Canalis, E TI Basic fibroblast growth factor (bFGF) downregulates osteonectin expression in osteoblasts by transcriptional mechanisms. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 ST FRANCIS HOSP & MED CTR,HARTFORD,CT 06105. NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP T413 EP T413 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501230 ER PT J AU Dieudonne, S Xu, T Chou, J Kuznetsov, S Robey, PG Young, M AF Dieudonne, S Xu, T Chou, J Kuznetsov, S Robey, PG Young, M TI Immortalization of marrow stromal fibroblasts from a patient with a null mutation in the estrogen receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BRB,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP T520 EP T520 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501337 ER PT J AU Kuznetsov, SA Riminucci, M Shenker, A Liu, B Spiegel, A Robey, PG AF Kuznetsov, SA Riminucci, M Shenker, A Liu, B Spiegel, A Robey, PG TI Mutation of Gs alpha in the bone microenvironment from patients with McCune-Albright syndrome SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NIDDK,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1996 VL 11 SU 1 BP T342 EP T342 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA495 UT WOS:A1996VA49501160 ER PT J AU Kelley, CA Sellers, JR Gard, DL Bui, D Adelstein, RS Baines, IC AF Kelley, CA Sellers, JR Gard, DL Bui, D Adelstein, RS Baines, IC TI Xenopus nonmuscle myosin heavy chain isoforms have different subcellular localizations and enzymatic activities SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; IMMUNOFLUORESCENCE MICROSCOPY; ACANTHAMOEBA-CASTELLANII; MITOTIC SPINDLE; CLEAVAGE FURROW; CELLULAR MYOSIN; MESSENGER-RNAS; B ISOFORM; CELLS; ACTIN AB There are two isoforms of the vertebrate nonmuscle myosin heavy chain, MHC-A and MHC-B, that are encoded by two separate genes. We compared the enzymatic activities as well as the subcellular localizations of these isoforms in Xenopus cells, MHC-A and MHC-B were purified from cells by immunoprecipitation with isoform-specific peptide antibodies followed by elution with their cognate peptides. Using an in vitro motility assay, we found that the velocity of movement of actin filaments by MHC-A was 3.3-fold faster than that by MHC-B. Likewise, the V-max of the actin-activated Mg2+-ATPase activity of MHC-A was 2.6-fold greater than that of MHC-B. Immunofluorescence microscopy demonstrated distinct localizations for MHC-A and MHC-B. In interphase cells, MHC-B was present in the cell cortex and diffusely arranged in the cytoplasm. In highly polarized, rapidly migrating interphase cells, the lamellipodium was dramatically enriched for MHC-B suggesting a possible involvement of MHC-B based contractions in leading edge extension and/or retraction. In contrast, MHC-A was absent from the cell periphery and was arranged in a fibrillar staining pattern in the cytoplasm, The two myosin heavy chain isoforms also had distinct localizations throughout mitosis. During prophase, the MHC-B redistributed to the nuclear membrane, and then resumed its interphase localization by metaphase. MHC-A, while diffuse within the cytoplasm at all stages of mitosis, also localized to the mitotic spindle in two different cultured cell lines as well as in Xenopus blastomeres, During telophase both isoforms colocalized to the contractile ring. The different subcellular localizations of MHC-A and MHC-B, together with the data demonstrating that these myosins have markedly different enzymatic activities, strongly suggests that they have different functions. C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV UTAH,DEPT BIOL,SALT LAKE CITY,UT 84112. RP Kelley, CA (reprint author), NHLBI,MOL CARDIOL LAB,NIH,BLDG 10,ROOM 8N-202,BETHESDA,MD 20892, USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 47 TC 130 Z9 131 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1996 VL 134 IS 3 BP 675 EP 687 DI 10.1083/jcb.134.3.675 PG 13 WC Cell Biology SC Cell Biology GA VB682 UT WOS:A1996VB68200008 PM 8707847 ER PT J AU Reynolds, K Zimmer, AM Zimmer, A AF Reynolds, K Zimmer, AM Zimmer, A TI Regulation of RAR beta 2 mRNA expression: Evidence for an inhibitory peptide encoded in the 5'-untranslated region SO JOURNAL OF CELL BIOLOGY LA English DT Article ID OPEN READING FRAMES; GCN4 MESSENGER-RNA; RETINOIC ACID; TRANSLATIONAL CONTROL; EUKARYOTIC RIBOSOMES; SECONDARY STRUCTURE; TRANSGENIC MICE; RXR-ALPHA; INITIATION; UPSTREAM AB Regulation of mRNA translation and stability plays an important role in the control of gene expression during embryonic development, We have recently shown that the tissue-specific expression of the RAR beta 2 gene in mouse embryos is regulated at the translational level by short upstream open reading frames (uORFs) In the 5'-untranslated region (Zimmer, A., A,M. Zimmer, and K. Reynolds. 1994. J. Cell Biol, 127:1111-1119). To gain insight into the molecular mechanism, we have performed a systematic mutational analysis of the uORFs. Two series of constructs were tested: in one series, each uORF was individually inactivated by introducing a point mutation in its start codon in the second series, all but one ORF were inactivated, Our results indicate that individual uORFs may have different functions, uORF4 seems to inhibit translation of the major ORF in heart and brain, while uORFs 2 and 5 appear to be important for efficient translation in all tissues. To determine whether the polypeptide encoded by uORF4 or the act of translating it, is the significant event, we introduced point mutations to create silent mutations or amino acid substitutions in uORF4. Our results indicate that the uORF4 amino acid coding sequence is important for the inhibitory effect on translation of the downstream major ORF. C1 NIMH,DEV BIOL UNIT,CELL BIOL LAB,BETHESDA,MD 20892. RI Zimmer, Andreas/B-8357-2009 NR 45 TC 59 Z9 59 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1996 VL 134 IS 4 BP 827 EP 835 DI 10.1083/jcb.134.4.827 PG 9 WC Cell Biology SC Cell Biology GA VD431 UT WOS:A1996VD43100002 PM 8769409 ER PT J AU Radhakrishna, H Klausner, RD Donaldson, JG AF Radhakrishna, H Klausner, RD Donaldson, JG TI Aluminum fluoride stimulates surface protrusions in cells overexpressing the ARF6 GTPase SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ADP-RIBOSYLATION FACTOR; RECEPTOR-MEDIATED ENDOCYTOSIS; ACTIN STRESS FIBERS; GOLGI MEMBRANES; PHOSPHOLIPASE-D; BREFELDIN-A; BINDING-PROTEIN; GUANINE-NUCLEOTIDE; BETA-COP; ACTIVATION AB To study the effector function of the ADP-ribosylation factor (ARF) 6 GTP-binding protein, we transfected HeLa cells with wild-type, epitope-tagged ARF6. Previously shown to indirectly activate the ARF1 GTPase, aluminum fluoride (AIF) treatment of ARF6-transfected cells resulted in a redistribution of both ARF6 and actin to discrete sites on the plasma membrane, which became increasingly protrusive over time. The effects of AlF were reversible, specific to cells transfected with wild-type ARF6, and resembled the cellular protrusions observed in cells expressing the GTPase defective mutant of ARF6. Importantly, the protrusions observed in cells transfected with ARF6 were distinct from the enhanced stress fibers and membrane ruffles observed in cells transfected with RhoA and Rad, respectively, In cells forming protrusions, there was an apparent stimulation of macropinocytosis and membrane recycling within the protrusive structures, In contrast, no block in transferrin uptake or alteration of the distribution of clathrin AP-2 complexes was detected in these cells. The AlF-induced, ARF6-dependent formation of protrusive structures was blocked by cytochalasin D and inhibitors of the lipoxygenase pathway. These observations support a novel role for the ARF6 GTPase in modeling the plasma membrane and underlying cytoskeleton. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. NR 59 TC 199 Z9 199 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1996 VL 134 IS 4 BP 935 EP 947 DI 10.1083/jcb.134.4.935 PG 13 WC Cell Biology SC Cell Biology GA VD431 UT WOS:A1996VD43100011 PM 8769418 ER PT J AU Goldman, RD Khuon, S Chou, YH Opal, P Steinert, PM AF Goldman, RD Khuon, S Chou, YH Opal, P Steinert, PM TI The function of intermediate filaments in cell shape and cytoskeletal integrity SO JOURNAL OF CELL BIOLOGY LA English DT Article ID EPIDERMOLYSIS-BULLOSA SIMPLEX; MICROTUBULE-ASSOCIATED PROTEINS; CULTURED FIBROBLASTS; CYTOPLASMIC FIBERS; SMOOTH-MUSCLE; IN-VIVO; VIMENTIN; KERATIN; SEQUENCE; NETWORKS AB This study describes the development and use of a specific method for disassembling intermediate filament (IF) networks in living cells. It takes advantage of the disruptive effects of mimetic peptides derived from the amino acid sequence of the helix initiation 1A domain of IF protein chains. The results demonstrate that at 1:1 molar ratios, these peptides disassemble vimentin IF into small oligomeric complexes and monomers within 30 min at room temperature in vitro. Upon microinjection into cultured fibroblasts, these same peptides induce the rapid disassembly of IF networks. The disassembly process is accompanied by a dramatic alteration in cell shape and the destabilization of microtubule and actin-stress fiber networks. These changes in cell shape and IF assembly states are reversible. The results are discussed with respect to the roles of IF in cell shape and the maintenance of the integrity and mechanical properties of the cytoplasm, as well as the stability of the other major cytoskeletal systems. C1 NIAMSD,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. RP Goldman, RD (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT CELL & MOL BIOL,303 E CHICAGO AVE,CHICAGO,IL 60611, USA. NR 76 TC 232 Z9 238 U1 1 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1996 VL 134 IS 4 BP 971 EP 983 DI 10.1083/jcb.134.4.971 PG 13 WC Cell Biology SC Cell Biology GA VD431 UT WOS:A1996VD43100014 PM 8769421 ER PT J AU Strouboulis, J Wolffe, AP AF Strouboulis, J Wolffe, AP TI Functional compartmentalization of the nucleus SO JOURNAL OF CELL SCIENCE LA English DT Review DE nucleus; compartmentalization; chromosome; replication; transcription; splicing; nuclear export ID PRE-MESSENGER-RNA; ACUTE PROMYELOCYTIC LEUKEMIA; MAMMALIAN-CELL NUCLEI; DNA-REPLICATION; RIBOSOMAL-RNA; INTRANUCLEAR DISTRIBUTION; XENOPUS-LAEVIS; COILED BODIES; POLYMERASE-II; HELA-CELLS AB Recent applications of cell biology and molecular genetics have built an image of nuclear organization in which the molecular machines involved in transcription, RNA processing and replication assemble morphologically distinct nuclear organelles with defined functional properties. These observations indicate a very high level of structural organization for the various metabolic activities occurring within the nucleus. We discuss the possible existence of novel regulatory functions inherent to nuclear architecture itself. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. NR 114 TC 119 Z9 120 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG PY 1996 VL 109 BP 1991 EP 2000 PN 8 PG 10 WC Cell Biology SC Cell Biology GA VC215 UT WOS:A1996VC21500002 PM 8856494 ER PT J AU Hoffman, MP Kibbey, MC Letterio, JJ Kleinman, HK AF Hoffman, MP Kibbey, MC Letterio, JJ Kleinman, HK TI Role of laminin-1 and TGF-beta 3 in acinar differentiation of a human submandibular gland cell line (HSG) SO JOURNAL OF CELL SCIENCE LA English DT Article DE HSG cell; acinar differentiation; matrigel; laminin-1; basement membrane; TGF-beta 3; salivary gland ID GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; BASEMENT-MEMBRANES; TGF-BETA; EXPRESSION; CLONING; FORMS; FACTOR-BETA-1; LOCALIZATION; APOPTOSIS AB Previous studies show that culturing an immortalized human submandibular gland cell line (HSG) on Matrigel, a basement membrane extract, induces cytodifferentiation. We have further defined this model system and identified factors involved in HSG cell acinar development and cytodifferentiation. Acinar development is marked by cell migration into multi-cellular spherical structures, cell proliferation and apoptosis of the centrally localized cells, In addition, functional differentiation was determined by indirect immunofluorescence and immunoblot analysis for cystatin, a salivary gland acinar cell-specific protein found to be produced by differentiated HSG cells. Matrigel contains multiple extracellular matrix proteins, however, laminin-1 was identified as the major matrix component that induced HSG cell acinar development and cytodifferentiation, Antibodies against specific components of Matrigel and against cell surface adhesion molecules were added to cells in culture to identify components important for HSG cell acinar differentiation. Immunostaining of HSG cell acini identified TGF-beta 2 and beta 3 as the predominant isoforms within the cells, Neutralizing antibodies directed against TGF-beta 3 significantly decreased (P less than or equal to 0.0002) the size of acini formed, These results indicate that multiple components, including laminin-1 and TGF-beta 3, contribute to HSG cell acinar development, This model system will be useful to study acinar differentiation and salivary gland-specific protein expression in vitro. C1 NIDR,CELL BIOL SECT,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. IGEN INC,GAITHERSBURG,MD 20877. NR 50 TC 114 Z9 116 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG PY 1996 VL 109 BP 2013 EP 2021 PN 8 PG 9 WC Cell Biology SC Cell Biology GA VC215 UT WOS:A1996VC21500005 PM 8856497 ER PT J AU Hummer, G Szabo, A AF Hummer, G Szabo, A TI Calculation of free-energy differences from computer simulations of initial and final states SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PHOTOSYNTHETIC REACTION CENTER; ELECTRON-TRANSFER; MOLECULAR-DYNAMICS; IONIZABLE GROUPS; PROTEINS; HYDRATION; WATER; MODEL; POTENTIALS; LYSOZYME AB A class of simple expressions of increasing accuracy for the free-energy difference between two states is derived based on numerical thermodynamic integration. The implementation of these formulas requires simulations of the initial and fnal (and possibly a few intermediate) states. They involve higher free-energy derivatives at these states which are related to the moments of the probability distribution of the perturbation. Given a specified number of such derivatives, these integration formulas are optimal in the sense that they are exact to the highest possible order of free-energy perturbation theory. The utility of this approach is illustrated for the hydration free energy of water. This problem provides a quite stringent test because the free energy is a highly nonlinear function of the charge so that even fourth order perturbation theory gives a very poor estimate of the free-energy change. Our results should prove most useful for complex, computationally demanding problems where foe-energy differences arise primarily from changes in the electrostatic interactions (e.g., electron transfer, charging of ions, protonation of amino acids in proteins). (C) 1996 American Institute of Physics. C1 LOS ALAMOS NATL LAB, CTR NONLINEAR STUDIES, LOS ALAMOS, NM 87545 USA. NIDDKD, CHEM PHYS LAB, NIH, BETHESDA, MD 20892 USA. RP Hummer, G (reprint author), LOS ALAMOS NATL LAB, THEORET BIOL & BIOPHYS GRP T10, MS K710, LOS ALAMOS, NM 87545 USA. RI Szabo, Attila/H-3867-2012; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 45 TC 114 Z9 116 U1 4 U2 24 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD AUG 1 PY 1996 VL 105 IS 5 BP 2004 EP 2010 DI 10.1063/1.472068 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA UZ525 UT WOS:A1996UZ52500026 ER PT J AU BruckerDavis, F Skarulis, MC Pikus, A Ishizawar, D Mastroianni, MA Koby, M Weintraub, BD AF BruckerDavis, F Skarulis, MC Pikus, A Ishizawar, D Mastroianni, MA Koby, M Weintraub, BD TI Prevalence and mechanisms of hearing loss in patients with resistance to thyroid hormone SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONGENITAL HYPOTHYROIDISM; OTOACOUSTIC EMISSIONS; RECEPTOR; KINDREDS; ORGAN; CORTI; FETAL; GENE; EAR AB Hearing impairment was anecdotally reported in resistance to thyroid hormone (RTH), a condition caused by mutations in the beta-thyroid hormone receptor (beta TR) gene. Because of its ontogenic distribution in the cochlea, the beta TR may have a pivotal role in the development of auditory function. To assess the prevalence and mechanisms of hearing impairment in RTH, 82 RTH-positive (RTH+) patients and 55 unaffected relatives (RTH-) underwent systematic audiological examination, including puretone and speech reception thresholds, and tests studying middle ear (tympanometry and acoustic reflexes), cochlear (otoacoustic emissions), and retrocochlear integrity (brain stem auditory evoked potentials). Significant hearing loss was present in 21% of RTH+ patients vs. none in RTH- patients. More RTH+ patients had abnormal tympanometry (34% vs. 12%) and abnormal acoustic reflexes (39% vs. 19%). Isolated conductive deficit was found in 7 of 17 RTH+ patients with hearing loss, isolated sensorineural deficit in 7 cases, and mixed deficit in 3 cases. Cochlear dysfunction was found in 50%, of all RTH+ patients, with or without hearing loss. Retrocochlear function was normal. No morphological cochlear abnormalities were detected on computed tomography of the temporal bone. In conclusion, hearing loss is a significant problem in RTH, with an equal frequency of conductive (probably related to the frequent ear infections) and sensorineural deficits. Abnormal otoacoustic emissions suggest that the mutant beta TR has a specific negative impact on cochlear function. C1 NATL INST DEAFNESS & OTHER COMMUN DISORDERS, NIH, CLIN AUDIOL SERV DIV, BETHESDA, MD 20982 USA. NIH, CTR CLIN, DEPT RADIOL, BETHESDA, MD 20892 USA. RP BruckerDavis, F (reprint author), NIDDK, MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BLDG 10, ROOM 8D14,10 CTR DR, MSC 1758, BETHESDA, MD 20892 USA. NR 35 TC 60 Z9 61 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1996 VL 81 IS 8 BP 2768 EP 2772 DI 10.1210/jc.81.8.2768 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VC901 UT WOS:A1996VC90100003 PM 8768826 ER PT J AU Bellantoni, MF Vittone, J Campfield, AT Bass, KM Harman, SM Blackman, MR AF Bellantoni, MF Vittone, J Campfield, AT Bass, KM Harman, SM Blackman, MR TI Effects of oral versus transdermal estrogen on the growth hormone/insulin-like growth factor I axis in younger and older postmenopausal women: A clinical research center study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-SECRETION; BINDING-PROTEIN; SOMATOMEDIN-C; REPLACEMENT THERAPY; BODY-COMPOSITION; AGE; RADIOIMMUNOASSAY; ESTRADIOL; SEX; GH AB To compare the effects of oral vs. transdermal estrogens on GH secretion and levels of circulating insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) in younger vs, older postmenopausal women, we conducted a placebo-controlled, cross-over trial of 6 weeks of oral conjugated estrogen (1.25 mg daily) or transdermal estradiol (100 mu g/day) administered in random order and separated by an 8-week, treatment-free interval. Sixteen healthy postmenopausal women, ages 49-75 yr, were studied on an NIH-funded General Clinical Research Center grant. Data were analyzed for the combined group as well as in the younger (less than or equal to 62 yr, n = 8) and older women (> 62 yr, n = 8). Spontaneous GH secretion, as assessed by 12-h overnight blood sampling at 20-min intervals; GH responsiveness to iv bolus injection of GHRH; and levels of serum IGF-I and IGFBP-3, before and after GHRH stimulation, were measured at enrollment and after 6 weeks of each estrogen treatment. Before estrogen treatment, spontaneous nocturnal GH secretion and morning IGF-I levels tended to be lower, IGFBP-3 levels did not differ, and GHRH-stimulated GB levels were significantly reduced in older vs. younger postmenopausal women. Oral estrogens increased spontaneous GH secretion, decreased serum IGF-I levels, and did not alter IGFBP-3 levels, whereas transdermal estrogens did not alter nocturnal GH secretion or morning IGF-I levels and decreased IGFBP-5 levels only in the older women. GHRH-stimulated GH levels were similar before and after oral or transdermal estrogen treatment. In contrast, after GHRH administration, IGF-I levels were decreased only with oral estrogens, whereas IGFBP-3 levels were decreased with both oral (younger women only) and transdermal (younger and older women) estrogens. We conclude that, in postmenopausal women, oral and transdermal estrogens exert differing effects on the GH/IGF-I axis, but neither form of estrogen completely reverses the known age-related reductions in spontaneous or GHRH-stimulated GH and IGF-I. C1 JOHNS HOPKINS BAYVIEW MED CTR, DEPT MED, BALTIMORE, MD 21224 USA. JOHNS HOPKINS BAYVIEW MED CTR, DEPT OBSTET & GYNECOL, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, BALTIMORE, MD 21224 USA. NIA, GERONTOL RES CTR, NIH, BALTIMORE, MD 21224 USA. JOHNS HOPKINS BAYVIEW MED CTR, DIV ENDOCRINOL & METAB, BALTIMORE, MD 21224 USA. JOHNS HOPKINS BAYVIEW MED CTR, DEPT MED, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED, BALTIMORE, MD 21224 USA. RP Bellantoni, MF (reprint author), JOHNS HOPKINS BAYVIEW MED CTR, GEN CLIN RES CTR, DIV GERIATR MED & GERONTOL, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. OI Bellantoni, Michele/0000-0001-8525-2247 FU NCRR NIH HHS [M01-RR-02719] NR 31 TC 106 Z9 107 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1996 VL 81 IS 8 BP 2848 EP 2853 DI 10.1210/jc.81.8.2848 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VC901 UT WOS:A1996VC90100019 PM 8768841 ER PT J AU Friedman, TC Yanovski, JA Nieman, LK Doppman, JL Cutler, GB Oldfield, EH Gold, PM Chrousos, GP Kalogeras, KT AF Friedman, TC Yanovski, JA Nieman, LK Doppman, JL Cutler, GB Oldfield, EH Gold, PM Chrousos, GP Kalogeras, KT TI Inferior petrosal sinus arginine vasopressin concentrations in normal volunteers and patients with Cushing's disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; CEREBROSPINAL-FLUID; SECRETION; ADRENOCORTICOTROPIN; STIMULATION; ADENOMAS AB In patients with Cushing's disease (CD), basal inferior petrosal sinus arginine vasopressin (AVP) concentrations are greater than peripheral levels and are further increased by the administration of CRH. AVP has an interpetrosal sinus gradient similar to that for ACTH, leading to the hypotheses that petrosal sinus AVP might either be derived from the corticotroph adenoma or be important for adenoma formation. To determine whether petrosal sinus AVP is truly increased in patients with CD, we compared inferior petrosal sinus and peripheral venous AVP and ACTH levels in 23 patients with CD and 9 healthy volunteers before and after iv ovine CRH. In both groups, AVP and ACTH showed interpetrosal lateralization, such that greater levels of both hormones were found at each time point in a single dominant petrosal sinus. When both hormones exhibited lateralization (an intersinus gradient >1.5), ACTH and AVP always lateralized together. In patients with CD, the ACTH interpetrosal sinus lateralization correctly identified the side of the pituitary containing the tumor in 75% of evaluable patients, whereas the AVP interpetrosal sinus lateralization identified 63% (P=NS). Ovine CRH stimulated AVP in both the dominant and nondominant petrosal sinuses in patients with CD. Although basal AVP in the dominant petrosal sinus was not significantly different in patients with CD and normal volunteers (144+/-85 vs. 13.0+/-4.3 pmol/L; P= 0.058), dominant petrosal sinus AVP was significantly elevated in patients with CD compared to normal volunteers at 3 min (269+/-122 vs. 45.1+/-30.0 pmol/L; P <0.05) and 5 min (315+/-120 vs. 40.2+/-23.6 pmol/L; P <0.05) after ovine CRH administration. Peripheral venous AVP levels were similar in all groups. We conclude that lateralization of AVP secretion occurs in both patients with CD and normal volunteers, but there is greater CRH-stimulated AVP secretion in the inferior petrosal sinuses of patients with CD. C1 NINCDS, OFF DIRECTOR, WARREN GRANT MAGNUSON CLIN CTR, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. NICHHD, DEV NEUROBIOL LAB, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. UNIV MISSISSIPPI, MED CTR, SCH MED, DEPT PSYCHIAT & HUMAN BEHAV, JACKSON, MS 39216 USA. RP Friedman, TC (reprint author), UNIV CALIF LOS ANGELES, DEPT MED,DIV ENDOCRINOL,SCH MED, CEDARS SINAI MED CTR, 8700 BEVERLY BLVD, LOS ANGELES, CA 90048 USA. NR 27 TC 11 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1996 VL 81 IS 8 BP 3068 EP 3072 DI 10.1210/jc.81.8.3068 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VC901 UT WOS:A1996VC90100055 PM 8768876 ER PT J AU Pahor, M Manto, A Pedone, C Carosella, L Guralnik, JM Carbonin, P AF Pahor, M Manto, A Pedone, C Carosella, L Guralnik, JM Carbonin, P TI Age and severe adverse drug reactions caused by nifedipine and verapamil SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE adverse drug reactions; calcium antagonists; nifedipine; verapamil; age; comorbidity ID ACUTE MYOCARDIAL-INFARCTION; OLDER PERSONS; STEREOSELECTIVE PHARMACOKINETICS; ELDERLY PATIENTS; ANGINA-PECTORIS; DOUBLE-BLIND; PHARMACODYNAMICS; DISPOSITION; THERAPY; TRIAL AB The association of age with risk for severe adverse drug reactions (SADRs) was studied in 2371 and 862 hospitalized patients taking nifedipine and verapamil, respectively. Nifedipine caused hypotension (n = 22), tachycardia (n = 3), and acute renal failure (n = 1) (total SADR rate, 1.1%, 26/2371). Verapamil caused hypotension (n = 3), bradycardia (n = 9), and atrioventricular blocks (n = 2) (total SADR rate, 1.6%, 14/862). The mean age of patients with and without SADRs was for nifedipine 77.1 +/- 1.7 and 71.8 +/- 0.8 years, respectively (p < 0.05), and for verapamil 73.4 +/- 2.9 and 73.1 +/- 0.4 years, respectively. Sex, length of stay, comorbidity, polypharmacy, intake of slow-release preparations, daily dosage, and new intake of calcium antagonists were examined as potential confounders of the age-SADR association. After adjusting for potential confounders, age was signficantly and independently associated with SADRs caused by nifedipine, but not with SADRs caused by verapamil (OR = 1.69, 95% CI = 1.05-2.72 and OR = 1.06, 95% CI = 0.63-1.68 for 10-year increase, respectively). Although nifedipine and verapamil did not have significantly different rates of SADRs, an age-related gradient was found only for nifedipine. C1 CATHOLIC UNIV,DEPT INTERNAL MED & GERIATR,I-00168 ROME,ITALY. NIA,EPIDEMDIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. RI Pedone, Claudio/F-9488-2010; OI Pedone, Claudio/0000-0003-1847-9032 NR 42 TC 17 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 1996 VL 49 IS 8 BP 921 EP 928 DI 10.1016/0895-4356(96)00056-X PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VB729 UT WOS:A1996VB72900016 PM 8699214 ER PT J AU Kleinman, HK Ponce, ML AF Kleinman, HK Ponce, ML TI The good side of side effects: Captopril blocks vessel and tumor growth SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID ANGIOGENESIS; CANCER RP Kleinman, HK (reprint author), NIDR,CELL BIOL SECT,NIH,BETHESDA,MD, USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 1 PY 1996 VL 98 IS 3 BP 599 EP 599 DI 10.1172/JCI118827 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VB698 UT WOS:A1996VB69800001 PM 8698847 ER PT J AU Wei, XX McLeod, HL McMurrough, J Gonzalez, FJ FernandezSalguero, P AF Wei, XX McLeod, HL McMurrough, J Gonzalez, FJ FernandezSalguero, P TI Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE DPD deficiency; 5-FU toxicity; population genotyping; exon skipping ID SEVERE FLUOROURACIL TOXICITY; THYMINE-URACILURIA; FAMILIAL PYRIMIDINEMIA; INBORN ERROR; SPLICE SITE; EXON; METABOLISM; POLYMORPHISM; CHEMOTHERAPY; PATIENT AB Dihydropyrimidine dehydrogenase (DPD) deficiency constitutes an inborn error in pyrimidine metabolism associated with thymine-uraciluria in pediatric patients and an increased risk of toxicity in cancer patients receiving 5-fluorouracil (5-FU) treatment. The molecular basis for DPD deficiency in a British family having a cancer patient that exhibited grade IV toxicity 10 d after 5-FU treatment was analyzed. A 165-bp deletion spanning a complete exon of the DPYD gene was found in some members of the pedigree having low DPD catalytic activity. Direct sequencing of lymphocyte DNA from these subjects revealed the presence of a G to A point mutation at the 5'-splicing site consensus sequence (GT to AT) that leads to skipping of the entire exon preceding the mutation during pre-RNA transcription and processing. A PCR-based diagnostic method was developed to determine that the mutation is found in Caucasian and Asian populations. This mutation was also detected in a Dutch patient with thymine-uraciluria and completely lacking DPD activity. A genotyping test for the G to A splicing point mutation could be useful in predicting cancer patients prone to toxicity upon administration of potentially toxic 5-FU and for genetic screening of heterozygous carriers and homozygous deficient subjects. C1 NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. UNIV ABERDEEN,DEPT MED & THERAPEUT,ABERDEEN AB9 2ZD,SCOTLAND. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 FU Wellcome Trust NR 27 TC 228 Z9 241 U1 2 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 1 PY 1996 VL 98 IS 3 BP 610 EP 615 DI 10.1172/JCI118830 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VB698 UT WOS:A1996VB69800004 PM 8698850 ER PT J AU Bhardwaj, N Seder, RA Reddy, A Feldman, MV AF Bhardwaj, N Seder, RA Reddy, A Feldman, MV TI IL-12 in conjunction with dendritic cells enhances antiviral CD8+ CTL responses in vitro SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE dendritic cells; cytolytic T cells; CD8+ T cells; interleukin 12; vaccines ID CYTOLYTIC LYMPHOCYTE-RESPONSES; STIMULATORY FACTOR NKSF; NATURAL-KILLER-CELLS; T-CELLS; INFLUENZA-VIRUS; IMMUNOREGULATORY FUNCTIONS; INTERLEUKIN-12 PRODUCTION; INTERFERON-GAMMA; CYTOKINE; GENERATION AB CD8+ cytolytic T lymphocytes (CTLs) are important mediators for resistance to infections and malignant diseases. IL-12 enhances proliferative and cytolytic responses by killer cells, but its function in the generation of human antiviral CD8+ T cell responses has not been defined. We therefore evaluated the role of IL-12 in the generation of CTLs to influenza-infected dendritic cells. IL-12 was not detectable in supernatants of infected-dendritic cells, or during CTL generation. Furthermore, anti-IL-12 antibody did not block CTL generation. However, exogenous IL-12 (30-300 pg/ml) enhanced CD8+ T cell proliferative and cytolytic responses. The effect was greatest in individuals with weak reactivity to influenza virus or at antigen-presenting cell (APC):T cell ratios of 1:100 or less. IL-12 augmented interferon-gamma production during CTL generation. The CTL enhancing effects of the cytokine, however, could not be blocked by neutralizing anti-interferon-gamma antibody. Together with IL-12, antigen-pulsed dendritic cells may be a useful approach for boosting CTL responses against infectious agents and malignancies. C1 HOSP SPECIAL SURG,NEW YORK,NY 10021. NIH,BETHESDA,MD 20892. RP Bhardwaj, N (reprint author), ROCKEFELLER UNIV,1230 YORK AVE,NEW YORK,NY 10021, USA. FU NIAMS NIH HHS [AR-42557, AR-39552] NR 43 TC 74 Z9 75 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG 1 PY 1996 VL 98 IS 3 BP 715 EP 722 DI 10.1172/JCI118843 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VB698 UT WOS:A1996VB69800017 PM 8698863 ER PT J AU Policastro, PF Peacock, MG Hackstadt, T AF Policastro, PF Peacock, MG Hackstadt, T TI Improved plaque assays for Rickettsia prowazekii in Vero76 cells SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INTRACELLULAR GROWTH-CYCLE; SPOTTED-FEVER GROUP; ACTIN POLYMERIZATION; ORGANISMS; ADHESION; IDENTIFICATION; INHIBITION; INFECTION; CULTURES; INVITRO AB Typhus group rickettsiae, including Rickettsia prowazekii and R. typhi, produce visible plaques on primary chick embryo fibroblasts and low-passage mouse embryo fibroblasts but do not form reproducible plaques on continuous cell culture lines, We tested medium overlay modifications for plaque formation of typhus group rickettsiae on the continuous fibroblast cell line Vero76, A procedure involving primary overlay with medium at pH 6.8, which was followed 2 to 3 days later with secondary overlay at neutral pH containing 1 mu g of emetine per ml and 20 mu g of NaF per ml, resulted in visible plaques at 7 to 10 days postinfection, A single-step procedure involving overlay with medium containing 50 ng of dextran sulfate per ml also resulted in plaque formation within 8 days postinfection, These assays represent reproducible and inexpensive methods for evaluating the infectious titers of typhus group rickettsiae, cloning single plaque isolates, and testing the susceptibilities of rickettsiae to antibiotics. RP Policastro, PF (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. NR 34 TC 12 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 1996 VL 34 IS 8 BP 1944 EP 1948 PG 5 WC Microbiology SC Microbiology GA UW859 UT WOS:A1996UW85900016 PM 8818887 ER PT J AU Miskovsky, EP Carrella, AV Gutekunst, K Sun, CA Quinn, TC Thomas, DL AF Miskovsky, EP Carrella, AV Gutekunst, K Sun, CA Quinn, TC Thomas, DL TI Clinical characterization of a competitive PCR assay for quantitative testing of hepatitis C virus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; TERM FOLLOW-UP; CHRONIC NON-A; RNA LEVELS; INFECTION; INTERFERON; CRYOGLOBULINEMIA; TRANSFUSION; ANTIBODY AB Rational clinical application of quantitative assessments of hepatitis C virus (HCV) RNA depends on an understanding of factors affecting the assay and its intrinsic variability, The effects of three types of blood collection tubes, two storage temperatures, five processing times, and two laboratories on a commercially available quantitative reverse transcriptase PCR assay (AMPLICOR HCV MONITOR) were evaluated. HCV RNA concentrations were assessed in 356 specimens representing 178 aliquots from nine patients. In a multivariate generalized linear model, HCV RNA concentrations decreased when centrifugation was delayed more than 6 h (P = 0.005) and were marginally different between laboratories (P = 0.06), but precentrifugation storage temperature (P = 1.00) and anticoagulation (P = 0.22) had no effect. After adjusting for other factors, the HCV concentration of 95% of a subject's samples were within 0.44 log. Specimens procured for reverse transcriptase PCR-based quantitative HCV testing should be centrifuged within 6 h of collection. Serial assessments should ideally be performed in the same laboratory, and changes in HCV RNA concentration of less than 0.44 log may not be biologically important. C1 JOHNS HOPKINS UNIV,SCH MED,DIV GASTROENTEROL & HEPATOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD. ROCHE MOL SYST,BRANCHBURG,NJ. NATL DEF MED CTR,SCH PUBL HLTH,TAIPEI,TAIWAN. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. FU NIDA NIH HHS [DA023201]; NIDDK NIH HHS [DK0129810] NR 22 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 1996 VL 34 IS 8 BP 1975 EP 1979 PG 5 WC Microbiology SC Microbiology GA UW859 UT WOS:A1996UW85900022 PM 8818893 ER PT J AU Gause, BL Sznol, M Kopp, WC Janik, JE Smith, JW Steis, RG Urba, WJ Sharfman, W Fenton, RG Creekmore, SP Holmlund, J Conlon, KC VanderMolen, LA Longo, DL AF Gause, BL Sznol, M Kopp, WC Janik, JE Smith, JW Steis, RG Urba, WJ Sharfman, W Fenton, RG Creekmore, SP Holmlund, J Conlon, KC VanderMolen, LA Longo, DL TI Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; METASTATIC MALIGNANT-MELANOMA; THYROID-DYSFUNCTION; ALPHA-INTERFERON; THERAPY; IMMUNOTHERAPY; TOXICITY; ANTIGENS; GAMMA AB Purpose: Although high-dose interleukin-2 (IL-2) can produce durable remissions in a subset of responding patients with renal cell carcinoma (RCC), this occurs in the setting of significant toxicity, The purpose of this study is to define the maximum-tolerated dosage (MTD) of IL-2 and interferon alfa-2a (IFN alpha-2a) that can be administered chronically on an outpatient basis. Patients and Methods: Fifty-three patients with advanced cancer of variable histology with good prognostic features were treated in six cohorts. Patients in cohorts one through five received IL-2 (1.5 or 3.0 x 10(6) million units (mU)/m(2)) Monday through Friday and IFN alpha-2a (1.5 or 3 x 10(6) mU/m(2)) daily for a 4-week cycle. In cohort six, IFN alpha-2a was given three times a week. Immunologic monitoring, including serum levels of soluble IL-2 receptor (sIL-2R) and neopterin, flow cytometry, and natural killer cell (NK) activity, were measured. Patients were evaluated for toxicity, response, and survival. Results: Almost all patients developed grade I/II toxicities commonly associated with cytokine therapy. Symptoms were most severe with the first treatment of each week. Dose-limiting toxicities included grade III fatigue, hypotension, and creatinine elevations. The MTD was 1.5 mU/m(2) daily x 5 given subcutaneously repeated weekly for IL-2 and 1.5 mU/m(2) daily subcutaneously (dose level 3) for IFN. Six of 25 assessable patients with RCC (24%) achieved a partial response (PR), including four of eight patients who were previously untreated. There were no objective responses in patients with other tumors, including 12 melanoma patients. Conclusion: IL-2 and IFN alpha-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC. C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. NATL CANC INST,FREDERICK CANC RES & DEV CTR,CLIN SERV PROGRAM,SCI APPLICAT INT CORP,FREDERICK,MD. RP Gause, BL (reprint author), NCI,BIOL RESPONSE MODIFIERS PROGRAM,CLIN RES BRANCH,DIV CANC TREATMENT,501 W 7TH ST,SUITE 3,FREDERICK,MD 21701, USA. NR 26 TC 28 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1996 VL 14 IS 8 BP 2234 EP 2241 PG 8 WC Oncology SC Oncology GA VA767 UT WOS:A1996VA76700007 PM 8708712 ER PT J AU Fyfe, GA Fisher, RI Rosenberg, SA Sznol, M Parkinson, DR Louie, AC AF Fyfe, GA Fisher, RI Rosenberg, SA Sznol, M Parkinson, DR Louie, AC TI Long-term response data for 255 patients with metastatic renal cell carcinoma treated with high-dose recombinant interleukin-2 therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 LOYOLA UNIV,MED CTR,MAYWOOD,IL 60153. NCI,BETHESDA,MD 20892. PRONEURON CORP,ROCKVILLE,MD. RP Fyfe, GA (reprint author), CHIRON CORP,4560 HORTON ST,EMERYVILLE,CA 94608, USA. NR 1 TC 100 Z9 101 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG PY 1996 VL 14 IS 8 BP 2410 EP 2411 PG 2 WC Oncology SC Oncology GA VA767 UT WOS:A1996VA76700040 PM 8708739 ER PT J AU Devlin, CL Smith, PJS AF Devlin, CL Smith, PJS TI A non-invasive vibrating calcium selective electrode measures acetylcholine-induced calcium flux across the sarcolemma of a smooth muscle SO JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL PHYSIOLOGY LA English DT Article DE Ca2+ channel blockers; cobalt chloride; diltiazem; excitation-contraction coupling; lanthanum chloride; smooth muscle; verapamil; vibrating Ca2+-selective electrode ID PIG VENTRICULAR MYOCYTES; BUSYCON-CANALICULATUM; DILTIAZEM; FIBERS; CA; DEPENDENCE; CHANNELS; NA AB To determine possible sources of Ca2+ during excitation-contraction coupling in smooth muscle, a vibrating Ca2+-selective electrode was used to measure Ca2+ flux during the process of contraction. The smooth muscle model was the longitudinal muscle of the body wall of a sea cucumber Sclerodactyla briareus. Because acetylcholine caused slow contractions of the muscle that were inhibited by Ca2+ channel blockers diltiazem and verapamil in earlier mechanical studies, we chose a vibrating Ca2+-selective electrode as our method to test the hypothesis that acetylcholine may be stimulating Ca2+ influx across the sarcolemma, providing a Ca2+ source during excitation-contraction coupling. Acetylcholine treatment stimulated a net Ca-2+ efflux that was both dose and time dependent. We then tested two L-type Ca2+ channel blockers, diltiazem and verapamil, and two non-specific Ca2+ blockers, cobalt (Co2+) and lanthanum (La3+) on acetylcholine-induced Ca2+ flux. All four Ca2+ blockers tested potently inhibited Ca2+ efflux induced by physiological doses of acetylcholine. We propose that the acetylcholine-induced Ca2+ efflux was the result of, first, Ca2+ influx through voltage-sensitive L-type Ca2+ channels, then the rapid extrusion of Ca2+ by an outwardly directed carrier such as the Na-Ca exchanger as suggested by Li+ substitution experiments. The vibrating Ca2+ electrode has provided new insights on the active and complex role the sarcolemma plays in Ca2+ homeostasis and regulating Ca2+ redistribution during excitation-contraction coupling. C1 MARINE BIOL LAB,NIH,NATL VIBRATING PROBE FACIL,WOODS HOLE,MA 02543. RP Devlin, CL (reprint author), PENN STATE UNIV,DEPT BIOL,ABINGTON,PA 19001, USA. NR 20 TC 9 Z9 9 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0174-1578 J9 J COMP PHYSIOL B JI J. Comp. Physiol. B-Biochem. Syst. Environ. Physiol. PD AUG PY 1996 VL 166 IS 4 BP 270 EP 277 DI 10.1007/BF00262871 PG 8 WC Physiology; Zoology SC Physiology; Zoology GA VG122 UT WOS:A1996VG12200004 PM 8810067 ER PT J AU Salas, SD Bennett, JE KwonChung, KJ Perfect, JR Williamson, PR AF Salas, SD Bennett, JE KwonChung, KJ Perfect, JR Williamson, PR TI Effect of the laccase gene, CNLAC1, on virulence of Cryptococcus neoformans SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MELANIN; PHENOLOXIDASE; MUTANTS; DNA AB To assess the relationship between melanin production by Cryptococcus neoformans and virulence on a molecular basis, we asked. (a) is CNLAC1, the laccase structural gene of C. neoformans, expressed in vivo?; (b) can mouse virulence be restored to cnlac1 (Mel(-)) mutants by complementation with CNLAC1?; and (c) will targeted gene deletion of CNLAC1 decrease virulence for mice! Melanin is produced when cryptococcal laccase catalyzes the oxidation of certain aromatic compounds, including L-dopa, to quinones, which then polymerize to melanin. To assess CNLAC1 transcription, RNA was extracted from C. neoformans in cerebrospinal fluid of infected rabbits. Reverse transcriptase-polymerase chain reaction detected CNLAC1 transcript, indicating that laccase may be produced in the infected host. To assess the effect of CNLAC1 deletion on virulence, a Mel(-) mutant (10S) was obtained by disruption of the 5' end oi the gene. After multiple backcrosses with 3 parental strain to remove unintended genetic defects introduced by the transformation process, 3 Mel(-) progeny was tested and found to be much less virulent for mice than a Mel(+) progeny. Another Mel(-) strain (mel2), obtained from J.C. Edman (University of California at San Francisco, CA), produced CNLAC1 transcript but Ilo detectable melanin. Characterization of this mutant revealed a base substitution in CNLAC1 that changed a histidine to tyrosine in a putative copper-binding site. When this base change was introduced into CNLAC1 by site-directed mutagenesis, it no longer transformed mel2 to Mel(+), indicating the importance of this histidine in laccase activity. Complementation of a mel2-derived mutant with CNLAC1 restored the Mel(+) phenotype and increased virulence. These results support the concept that the CNLAC1 gene product has a role in virulence. C1 NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,MOL MICROBIOL SECT,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. UNIV ILLINOIS,MED CTR,INFECT DIS SECT,CHICAGO,IL 60612. FU NIAID NIH HHS [AI 28388] NR 24 TC 250 Z9 260 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1996 VL 184 IS 2 BP 377 EP 386 DI 10.1084/jem.184.2.377 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700009 PM 8760791 ER PT J AU AlexanderMiller, MA Leggatt, GR Sarin, A Berzofsky, JA AF AlexanderMiller, MA Leggatt, GR Sarin, A Berzofsky, JA TI Role of antigen, CD8, and cytotoxic T lymphocyte (CTL) avidity in high dose antigen induction of apoptosis of effector CTL SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYTO-TOXIC LYMPHOCYTES; PROGRAMMED CELL-DEATH; SYNTHETIC PEPTIDES; COGNATE PEPTIDES; RECEPTOR; ACTIVATION; DELETION; PROLIFERATION; TOLERANCE; INVIVO AB Experimental data suggest that negative selection of thymocytes call occur as a result of supraoptimal antigenic stimulation. It is unknown, however, whether such mechanisms are at work in mature CD8(+) T lymphocytes. Here, we show that CD8(+) effector cytotoxic T lymphocytes (CTL) are susceptible to proliferative inhibition by high dose peptide antigen, leading to apoptotic death mediated by TNF-alpha release. Such inhibition is not reflected in the cytolytic potential of the CTL, since concentrations of antigen that are inhibitory for proliferation promote efficient lysis of:target cells. Thus, although CTL have committed to the apoptotic pathway, the kinetics of this process are such that CTL function can occur before death of the CTL. The concentration of antigen required for inhibition is a function of the CTL avidity, in that concentrations of antigen capable of completely inhibiting high avidity CTL maximally stimulate low avidity CTL. Importantly, the inhibition call be detected in both activated and resting CTL. Blocking studies demonstrate that the CD8 molecule contributes significantly to the inhibitory signal as the addition of anti-CD8 antibody restores the proliferative response. Thus, our data support the model that mature CD8(+) CTL can accommodate an activation signal of restricted intensity, which, if surpassed, results in deletion of that cell. C1 NCI, MOL IMMUNOGENET & VACCINE RES SECT, METAB BRANCH, NIH, BETHESDA, MD 20892 USA. NCI, EXPT IMMUNOL BRANCH, NIH, BETHESDA, MD 20892 USA. RI Leggatt, Graham/G-1924-2010; OI Leggatt, Graham/0000-0002-4078-5653 NR 42 TC 169 Z9 174 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1996 VL 184 IS 2 BP 485 EP 492 DI 10.1084/jem.184.2.485 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700020 PM 8760802 ER PT J AU Loftus, DJ Castelli, C Clay, TM Squarcina, P Marincola, FM Nishimura, MI Parmiani, G Appella, E Rivoltini, L AF Loftus, DJ Castelli, C Clay, TM Squarcina, P Marincola, FM Nishimura, MI Parmiani, G Appella, E Rivoltini, L TI Identification of epitope mimics recognized by CTL reactive to the melanoma/melanocyte-derived peptide MART-1(27-35) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; MYELIN BASIC-PROTEIN; HUMAN-MELANOMA; MOLECULAR MIMICRY; PERIPHERAL-BLOOD; ANTIGENIC PEPTIDE; HLA-A2 MELANOMAS; MHC COMPLEXES; CELL LINES AB CTL reactivity to the epitope MART-1((27-35)), of the melanoma (self) antigen MART-1/melan A is frequently observed in Tumor-infiltrating lymphocytes and may be readily elicited from the peripheral blood of melanoma patients that express HLA-A*0201. Available data suggest that these observations contrast with those made for other HLA-A*0201-presented melanoma self antigens regarding the regularity observed CTL responses. Based on preliminary findings, we hypothesized that the CTL response to MART-1 might be augmented in part by T cell encounters with peptides derived from sources other than MART-1, which show sequence similarity to MART-1((27-35)). To test this idea, a protein database search fur potential MART-1 epitope mimics was done using criteria developed from analyses of effector recognition of singley-substituted peptide analogues of MART-1((27-35)). Synthetic peptides were made for a portion of the sequences retrieved; 12/40 peptides tested were able to sensitize target cells for lysis by one or more anti-MART-1 effectors. The peptides recognized correspond to sequences occurring in a variety of proteins of viral, bacterial, and human (self) origin. One peptide derives from glycoprotein C of the common pathogen HSV-1; cells infected with recombinant vaccinia virus encoding native glycoprotein C were lysed by anti-MART-1 effectors. Our results overall indicate that sequences conforming to the A2.1 binding motif and possessing features essential to recognition by anti-MART-1 CTL occur frequently in proteins. These findings further suggest that T cells might encounter a variety of such sequences in vivo, and chat epitope mimicry may Flay a role in modulating the CTL response to MART-1((27-35)). C1 IST NAZL TUMORI, DIV EXPT ONCOL D, I-20133 MILAN, ITALY. NCI, NIH, SURG BRANCH, BETHESDA, MD 20892 USA. RP Loftus, DJ (reprint author), NATL CANC INST, CELL BIOL LAB, I-20133 MILAN, ITALY. RI castelli, chiara/K-6899-2012; OI castelli, chiara/0000-0001-6891-8350; Rivoltini, Licia/0000-0002-2409-6225 NR 59 TC 134 Z9 135 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1996 VL 184 IS 2 BP 647 EP 657 DI 10.1084/jem.184.2.647 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700036 PM 8760818 ER PT J AU Wu, WY Harley, PH Punt, JA Sharrow, SO Kearse, KP AF Wu, WY Harley, PH Punt, JA Sharrow, SO Kearse, KP TI Identification of CD8 as a peanut agglutinin (PNA) receptor molecule on immature thymocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MOUSE THYMOCYTES; IMMUNOGLOBULIN SUPERFAMILY; POSITIVE SELECTION; BINDING LECTIN; T-CELLS; GLYCOPROTEINS; DIFFERENTIATION; GLYCANS; EVENTS; MEMBER AB Differentiation of most T lymphocytes occurs within the thymus and is characterized by variable expression of CD4/CD8 coreceptor molecules, increased surface density of T cell antigen receptor (TCR) alpha beta proteins, and decreased expression of glycan chains recognized by the galactose-specific lectin peanut agglutinin (PNA). Although appreciated for several decades that PNA agglutination is useful for the physical separation of immature and mature thymocyte subpopulations, the identity of specific PNA-binding glycoproteins expressed on immature thymocytes remains to be determined. In the cut-rent report, we studied the expression of PNA-specific glycans on immature and mature T cells and used lectin affinity chromatography and immunoprecipitation techniques to characterize PNA-binding glycoproteins on thymocytes. Our data demonstrate that PNA-specific glycans are localized on a relatively small subset of thymocyte surface proteins, several of which were specifically identified, including CD43, CD45, and surprisingly, CD8 molecules. CD8 alpha and CD8 alpha' proteins bound to PNA in the absence of CD8 beta expression showing that O-glycans on CD8 beta glycoproteins are not necessary for PNA binding and that glycosylation of CD8 alpha and CD8 alpha' proteins proceeds effectively in the absence of CD8 beta. Finally, we demonstrate that PNA binding of CD8 is developmentally regulated by sialic acid addition as CD8 proteins from mature T cells bound to PNA only after sialidase treatment. These studies identify CD8 as a PNA receptor molecule on immature thymocytes and show that PNA binding of CD8 on immature and mature T cells is developmentally regulated by sialic acid modification. C1 NCI, EXPT IMMUNOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 28 TC 45 Z9 46 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1996 VL 184 IS 2 BP 759 EP 764 DI 10.1084/jem.184.2.759 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700049 PM 8760831 ER PT J AU Segal, BM Shevach, EM AF Segal, BM Shevach, EM TI IL-12 unmasks latent autoimmune disease in resistant mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; T-CELLS; MULTIPLE-SCLEROSIS; INTERFERON-GAMMA; SJL/J MICE; TH1 CELLS; SUPPRESSION; EXPRESSION; CYTOKINES AB Inbred mice exhibit a spectrum of susceptibility to induction of experimental allergic encephalomyelitis (EAE). We have compared the immune responses of thr susceptible SJL (H-2(s)) and resistant B10.S (H-2(s)) strains to determine factors other than the MHC background which control resistance/susceptibility to EAE. The resistance of the B10.S strain was found to be secondary to an antigen-specific defect in the generation of Th1 cells that produce IFN gamma. This defect in IFN gamma production could be restored by exposure of the myelin basic protein (MBP)-reactive T cells to IL-12 with the subsequent induction of the ability to transfer EAE to naive recipients. These findings have important implications for the therapeutic use of IL-12 and IL-12 antagonists and may explain the association between relapses/exacerbation of autoimmune disease and infectious diseases. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. OI Segal, Benjamin/0000-0002-0906-6319 NR 26 TC 141 Z9 143 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1996 VL 184 IS 2 BP 771 EP 775 DI 10.1084/jem.184.2.771 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VC337 UT WOS:A1996VC33700051 PM 8786337 ER PT J AU Ruvolo, VR Berneman, Z Secchiero, P Nicholas, J AF Ruvolo, VR Berneman, Z Secchiero, P Nicholas, J TI Cloning, restriction endonuclease mapping and partial sequence analysis of the genome of human herpesvirus 7 strain JI SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TELOMERIC REPEAT SEQUENCES; HUMAN CYTOMEGALOVIRUS; EXANTHEM-SUBITUM; CODING CONTENT; DNA-SEQUENCE; CAUSAL AGENT; IDENTIFICATION; VIRUS; PROTEIN; HETEROGENEITY AB Human herpesvirus 7 (HHV-7) is a recently isolated herpesvirus that has been shown to be related to human cytomegalovirus and human herpesvirus 6 and to be a member of the betaherpesvirus subgroup, Here we report the cloning, restriction endonuclease mapping and partial sequence analysis of HHV-7 strain JI DNA. Virus particles were obtained from the supernatant of infected SupT1 cells, the DNA isolated by proteinase K treatment-phenol extraction, and full-length viral DNA was purified and isolated on a pulsed-field gel. Aliquots of this highly purified material were treated in the following ways: (i) sonicated and end-repaired to create short randomly sheared fragments for cloning into M13mp 18-Smal vector DNA; (ii) cut with EcoRI for cloning into EcoRI-cut lambda ZAPII or lambda DASHII vectors; (iii) cut with BamHI for cloning into BamHI-cut lambda ZAP-Express or lambda DASHII vectors. Partial nucleotide sequencing of the M13 clones followed by detection of open reading frames and their translation allowed the identification of homologues through PASTA searches of the database. Relevant M13 clones were used as probes to isolate corresponding lambda phage clones, which could tentatively be mapped to the genome on the basis of presumed genetic collinearity between HHV-7 and HHV-6. Genomic 'walking' between EcoRI and BamHI lambda genomic libraries enabled overlapping neighbouring clones to be identified and mapped. Each of these clones was analysed to map BamHI, EcoRI, Sail, SmaI and XhoI restriction endonuclease sites to provide complete endonuclease maps for the entire genome. C1 JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21231. UNIV ANTWERP HOSP,B-2650 EDEGEM,BELGIUM. NIH,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 FU NIAID NIH HHS [R29 AI035483] NR 31 TC 13 Z9 13 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD AUG PY 1996 VL 77 BP 1901 EP 1912 DI 10.1099/0022-1317-77-8-1901 PN 8 PG 12 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA VA537 UT WOS:A1996VA53700036 PM 8760442 ER PT J AU Lafrenie, RM Wahl, LM Epstein, JS Hewlett, IK Yamada, KM Dhawan, S AF Lafrenie, RM Wahl, LM Epstein, JS Hewlett, IK Yamada, KM Dhawan, S TI HIV-1-Tat protein promotes chemotaxis and invasive behavior by monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONONUCLEAR PHAGOCYTES; AIDS PATIENTS; TAT PROTEINS; INFECTION; CELLS; MACROPHAGES AB Monocytes are susceptible to HIV infection and to activation by a regulatory gene product of the HIV genome, HIV-Tat. Recently, we have demonstrated that treatment with HIV-Tat up-regulates monocyte adhesion to the endothelium and increases metalloproteinase production. In the present study, we have examined the ability of the HIV-Tat protein to alter the migratory and invasive behavior of monocytes. Monocytes pretreated for 24 h with 10 ng/ml HIV-Tat exhibited enhanced migratory behavior compared with untreated monocytes in chemotaxis assays, both in the absence of a chemoattractant as well as in response to FMLP. In addition, HIV-Tat itself induced the migration of both untreated and HIV-Tat pretreated monocytes. Checkerboard analysis showed that monocytes migrated in response to an HIV-Tat concentration gradient, thus confirming the chemotactic characteristics of the HIV-Tat protein, Pretreatment of monocytes with 10 ng/ml HIV-Tat for 24 h also increased their ability to invade reconstituted extracellular membrane (Matrigel)coated filters by 5-fold in the absence of chemoattractant. The presence of FMLP or HIV-Tat further enhanced invasion by both untreated and HIV-Tat-pretreated monocytes by more than 10-fold. Monocyte invasion was partially inhibited by the inclusion of anti-beta(1) integrin Ab or tissue inhibitor of metalloproteinase (TIMP). Thus, for the first time, we present evidence that HIV-Tat can enhance the chemotactic and invasive behaviors of monocytes and propose an active role for HIV-Tat in the recruitment of monocytes into extravascular tissues, a process which may contribute to the destruction of tissues and cellular architecture often seen in patients with acquired immunodeficiency syndrome. C1 NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. US FDA,IMMUNOPATHOL SECT,MOL VIROL LAB,DIV TRANSFUS TRANSMITTED DIS,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. OI Yamada, Kenneth/0000-0003-1512-6805 NR 20 TC 110 Z9 111 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1996 VL 157 IS 3 BP 974 EP 977 PG 4 WC Immunology SC Immunology GA VG999 UT WOS:A1996VG99900002 PM 8757599 ER PT J AU Kenny, JJ Fischer, RT Lustig, A Dintzis, H Katsumata, M Reed, JC Longo, DL AF Kenny, JJ Fischer, RT Lustig, A Dintzis, H Katsumata, M Reed, JC Longo, DL TI bcl-2 alters the antigen-driven selection of B cells in mu kappa but not in mu-only Xid transgenic mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID REACTIVE LYMPHOCYTES-B; IMMUNE-DEFICIENT MICE; PHOSPHATIDYL CHOLINE; AUTOIMMUNE-DISEASE; ALLELIC EXCLUSION; IMMUNOGLOBULIN-MU; GENE-EXPRESSION; BONE-MARROW; CHAIN GENE; DEATH AB A point mutation in the pleckstrin homology domain of the mouse Bruton's tyrosine kinase (btk) gene results in an X-linked immune defect, Xid, characterized by immunologic unresponsiveness to polymeric carbohydrate Ags. In Xid mice, B cells specific for phosphocholine (PC) do not develop in peripheral lymphoid tissues because they either fail to be positively selected from the marrow or they are clonally deleted via an Ag-driven, receptor-mediated process, Overexpression of the bd-2 gene allows PC-specific B cells to survive and mature in Xid mu kappa anti-PC transgenic mice, but PC-specific B cells are not rescued by bd-2 in Xid mu-only transgenic mice. The failure of bd-2 to rescue PC-specific B cells in mu-only transgenic mice suggests that either it does not correct the btk defect in the Ag-driven selection process that occurs in pre-B cells and/or in very immature B cells or that a btk-dependent proliferative phase is required for the selection and amplification of the PC-specific B cells in mu-only transgenic mice. The rescue of PC-specific B cells in mu kappa transgenic mice indicates that bd-2 can alter receptor-mediated B cell selection at late stages in B cell development, The rescued PC-specific B cells in Xid male mice do not exhibit an altered proliferation profile in response to B cell-stimulating agents compared with B cells from unmanipulated Xid mice; thus, they fail to respond to soluble anti-mu or PC-dextran hut they proliferate in response to PC, anti-mu, or anti-ld conjugated to Sepharose. C1 CTR CANC RES,LA JOLLA CANC RES FDN,LA JOLLA,CA 92037. UNIV PENN,SCH MED,DEPT PATHOL,PHILADELPHIA,PA 19104. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOPHYS,BALTIMORE,MD 21205. NCI,BIOCHEM PHYSIOL LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. SCI APPLICAT INT CORP,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD. RP Kenny, JJ (reprint author), NIA,GERONTOL RES CTR,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 58 TC 13 Z9 13 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1996 VL 157 IS 3 BP 1054 EP 1061 PG 8 WC Immunology SC Immunology GA VG999 UT WOS:A1996VG99900012 PM 8757609 ER PT J AU Tian, JH Miller, LH Kaslow, DC Ahlers, J Good, MF Alling, DW Berzofsky, JA Kumar, S AF Tian, JH Miller, LH Kaslow, DC Ahlers, J Good, MF Alling, DW Berzofsky, JA Kumar, S TI Genetic regulation of protective immune response in congenic strains of mice vaccinated with a subunit malaria vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; TUMOR-NECROSIS-FACTOR; SUPPRESSOR T-CELLS; PLASMODIUM-YOELII; MONOCLONAL-ANTIBODY; AOTUS MONKEYS; ANTIGEN; PURIFICATION; FRAGMENT; PARASITE AB The C-terminal 19-kDa, epidermal growth factor-like region of the merozoite surface protein 1 (MSP1) has been used as a vaccine to induce protective immunity to Plasmodium yoelii in mice and to Plasmodium falciparum in monkeys, To analyze the mechanisms and genetic regulation of this MSP1 vaccine-induced protection, we studied the immunologic correlates of protection in H-2 recombinant and congenic mouse strains on the B10 background, Multiple H-2-linked loci were round to contribute, each with a different mechanism. One locus mapped to the I-A region based onthe strong protection in C57BL/10 mice compared with intermediate protection in B10.A(4R) mice and the lack of a difference between B10.AKM and B10.MBR mice, Differences in efficacy of passively transferred antisera from vaccinated C57BL/10 vs B10.A(4R) mice indicated that the protection regulated by the I-A locus was at least in part Ab dependent, Two loci mapped to the right of I-A (I-E, H-2S, or H-2D) based on a correlation with the number of H-2(k) loci to the right of I-A in mice that were I-A(k). One effect was Ab independent and may correspond to a possible negative effect of the I-E(k) locus, T cells from protected and nonprotected strains differed in their production of IFN-gamma and TNF-alpha following immunization with MSP1(19), but it was unclear how the differential patterns of cytokine expression related to the level of protection, Thus, MSP1(19) vaccine-induced protection is regulated by H-2-linked loci corresponding to two different immune mechanisms, These findings may indicate the need for more than one Ag in a vaccine to protect an HLA-diverse population. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NIAID,OFF SCI DIRECTOR,NIH,BETHESDA,MD 20892. NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. QUEENSLAND INST MED RES,COOPERAT RES CTR VACCINE TECHNOL,BRISBANE,QLD 4006,AUSTRALIA. NR 30 TC 61 Z9 63 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1996 VL 157 IS 3 BP 1176 EP 1183 PG 8 WC Immunology SC Immunology GA VG999 UT WOS:A1996VG99900026 PM 8757623 ER PT J AU Fuss, IJ Neurath, M Boirivant, M Klein, JS delaMotte, C Strong, SA Fiocchi, C Strober, W AF Fuss, IJ Neurath, M Boirivant, M Klein, JS delaMotte, C Strong, SA Fiocchi, C Strober, W TI Disparate CD4(+) lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease - Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4+ T-CELLS; INTERFERON-GAMMA; FUNCTIONAL-CHARACTERIZATION; SCID MICE; LYMPHOCYTES; ACTIVATION; SUBSETS; GENE; DIFFERENTIATION; INHIBITION AB In this study, we investigate whether human inflammatory bowel disease (IBD) (ulcerative colitis and Crohn's disease) is associated with altered lymphokine secretion profiles, as recently found in various animal models oi chronic intestinal inflammation. In initial studies, we determined the proliferative responses of purified lamina propria (LP) CD4(+) T cells from patients with IBD under defined conditions of T cell stimulation. We found that IBD LP CD4(+) T cells in comparison with control LP CD4(+) T cells have diminished TCR/CD3 pathway proliferative responses, whereas CD2/CD28 accessory pathway proliferative responses are relatively preserved. In further studies centering on lymphokine production, we showed that LP T cells from inflamed Crohn's disease mucosa manifest increased IFN-gamma secretion compared with control LP T cells, particularly when stimulated via the CD2/CD28 pathway. Subsequent ELISPOT analysis indicated that this was due to an increased number of IFN-gamma-secreting CD4(+) T cells, In contrast, IL-4 and IL-5 production by Crohn's disease LP T cells was decreased compared with that of control LP T cells. Of interest, IL-2 production by Crohn's disease LP T cells was also reduced, as was IL-2 production by peripheral blood T cells. In parallel studies, LP T cells hom inflamed ulcerative colitis mucosa stimulated via either the TCR/CD3/CD28 or CD2/CD28 produced increased amounts of IL-5, again when measured either as secreted IL-5 or by ELISPOT analysis. Such increased IL-5 production was not associated with increased IL-4 secretion and, in contrast to Crohn's disease, ulcerative colitis LP T cell production of IL-2 and IFN-gamma was normal. Taken together, these studies provide strong evidence that the immunopathologic process characteristic of the two major forms of IBD is associated with very different cytokine secretion patterns, These different patterns may determine the type of inflammatory process present. C1 NIAID, MUCOSAL IMMUN SECT, CLIN INVEST LAB, NIH, BETHESDA, MD 20892 USA. CLEVELAND CLIN FDN, DEPT COLORECTAL SURG, CLEVELAND, OH 44195 USA. CLEVELAND CLIN FDN, RES INST, CLEVELAND, OH 44195 USA. RI BOIRIVANT, MONICA/B-9977-2016 NR 44 TC 859 Z9 884 U1 0 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1996 VL 157 IS 3 BP 1261 EP 1270 PG 10 WC Immunology SC Immunology GA VG999 UT WOS:A1996VG99900037 PM 8757634 ER PT J AU Goletti, D Weissman, D Jackson, RW Graham, NMH Vlahov, D Klein, RS Munsiff, SS Ortona, L Cauda, R Fauci, AS AF Goletti, D Weissman, D Jackson, RW Graham, NMH Vlahov, D Klein, RS Munsiff, SS Ortona, L Cauda, R Fauci, AS TI Effect of Mycobacterium tuberculosis on HIV replication - Role of immune activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELLS; PULMONARY TUBERCULOSIS; CLINICAL-FEATURES; INCUBATION PERIOD; LYMPHOID-TISSUE; INFECTION; LYMPHOCYTES; DISEASE; TYPE-1 AB The prevalence of Mycobacterium tuberculosis (MTB)(3) has increased worldwide, in part due to the HIV epidemic, Epidemiology data have demonstrated that HIV-infected individuals are more susceptible to MTB disease, which may lead to an acceleration in the progression of HIV disease, The purpose of this study was to determine whether MTB modulates HIV infection in vivo and to delineate the mechanisms involved by using in vitro model systems, Plasma viral load was measured in HIV-infected individuals before, during, and after the development of MTB disease; a 5- to 160-fold increase in viral replication was observed during the acute phase of MTB disease, In order to evaluate the mechanisms involved in this MTB-induced HIV replication, we used an in vitro system of primary PBMC and lymph node mononuclear cells isolated from HIV-infected individuals. The data demonstrated that MTB induced HIV replication in CD8(+) T cell-depleted lymphocytes from HIV-infected individuals with a history of purified protein derivative (PPD) positivity but not in those who were PPD negative; this induction of HIV replication correlated with the level of cellular activation. In an in vitro acute HIV infection model, MTB increased HIV replication in PBMC from healthy donors with a history of PPD positivity, but not in PBMC from PPD-negative donors and this induction of viral replication also correlated with cellular activation. In conclusion, MTB increased HIV replication in vivo and in an in vitro model. This MTB-mediated viral production likely occurs through Ag-specific activation and infection of responding T cells. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. ALBERT EINSTEIN COLL MED,MONTEFIORE MED CTR,DEPT MED,DIV INFECT DIS,BRONX,NY 10467. ALBERT EINSTEIN COLL MED,MONTEFIORE MED CTR,DEPT EPIDEMIOL & SOCIAL MED,BRONX,NY 10467. CATHOLIC UNIV,DEPT INFECT DIS,ROME,ITALY. RP Goletti, D (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,RM 6A33,10 CTR DR,MSC 1576,BETHESDA,MD 20892, USA. OI Goletti, Delia/0000-0001-8360-4376 FU NIDA NIH HHS [DA04334, DA07061]; PHS HHS [N01/A0/42701] NR 55 TC 364 Z9 371 U1 0 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1996 VL 157 IS 3 BP 1271 EP 1278 PG 8 WC Immunology SC Immunology GA VG999 UT WOS:A1996VG99900038 PM 8757635 ER PT J AU McCartneyFrancis, NL Mizel, DE Redman, RS FrazierJessen, M Panek, RB Kulkarni, AB Ward, JM McCarthy, JB Wahl, SM AF McCartneyFrancis, NL Mizel, DE Redman, RS FrazierJessen, M Panek, RB Kulkarni, AB Ward, JM McCarthy, JB Wahl, SM TI Autoimmune Sjogren's-like lesions in salivary glands of TGF-beta 1-deficient mice are inhibited by adhesion-blocking peptides SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; SYSTEMIC LUPUS-ERYTHEMATOSUS; B-CELL ACTIVATION; FIBRONECTIN PEPTIDES; KNOCKOUT MICE; MRL/LPR MICE; NULL MICE; EXPRESSION; DISEASE; PATHOGENESIS AB The targeted disruption of the TGF-beta 1 gene in mice (TGF-beta 1 -/-) leads to extensive inflammation in vital organs, cachexia, and death within 3 to 4 wk. Significant inflammatory lesions develop initially in the periductal regions of the salivary glands and escalate as the animals become symptomatic. These inflammatory shes, characterized by lymphocytic infiltration and increased proliferation, cytokine mRNA expression, and IgG-positive cells, resemble lesions of Sjogren's syndrome. Moreover, the inflammatory pathology, enhanced MHC expression, and Ab production are consistent with an autoimmune-like etiology. Glandular atrophy and loss of acini with reduced saliva production appear to contribute to the wasting syndrome characteristic of the TGF-beta 1 -/- mice, To determine whether the structural and functional defects were developmental due to the absence of TGF-beta 1 or secondary to the inflammation, TGF-beta 1 -/- mice were treated with synthetic fibronectin peptides, which block leukocyte infiltration. Daily systemic injections of RGD, CS-1, and/or peptides derived from the heparin-binding region of the A chain not only prevented leukocyte infiltration in the salivary glands of the TGF-beta 1 -/- mite, but also reversed the acinar and ductal derangements, These data suggested that salivary gland development is not jeopardized in the absence of TGF-beta 1, but that the extensive infiltration of inflammatory cells compromises glandular structure and function, The essential nature of TGF-beta 1 in controlling inflammatory and immune processes is confirmed by these studies. Moreover, these TGF-beta 1 -/- mice provide an important model of autoimmune disease that can be used in the design of therapeutic interventions. C1 NIDA, GENE TARGETING RES & CORE FACIL, NIH, BETHESDA, MD 20892 USA. DEPT VET AFFAIRS MED CTR, ORAL PATHOL RES LAB, WASHINGTON, DC 20422 USA. NCI, OFF LAB ANIM SCI, FREDERICK, MD 21702 USA. UNIV MINNESOTA, LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA. RP McCartneyFrancis, NL (reprint author), NIDA, CELLULAR IMMUNOL SECT,IMMUNOL LAB,NIH, 30 CONVENT DR, MSC 4352, BETHESDA, MD 20892 USA. NR 39 TC 47 Z9 48 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1996 VL 157 IS 3 BP 1306 EP 1312 PG 7 WC Immunology SC Immunology GA VG999 UT WOS:A1996VG99900042 PM 8757639 ER PT J AU Young, HA AF Young, HA TI Regulation of interferon-gamma gene expression SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Review ID NF-KAPPA-B; T-CELLS; PROMOTER; METHYLATION; ACTIVATION; ELEMENTS; BINDING; DNA AB Interferon-gamma (IFN-gamma), also known as type II interferon, is an important immunoregulatory gene that has multiple effects on the development, maturation, and function of the immune system, IFN-gamma mRNA and protein are expressed predominantly by T cells and large granular lymphocytes. The IFN-gamma mRNA is induced/inhibited in these cell types by a wide variety of extracellular signals, thus implicating a number of diverse, yet convergent signal transduction pathways in its transcriptional control, In this review, I describe how DNA methylation and specific DNA binding proteins may regulate transcription of the IFN-gamma gene in response to extracellular signals. RP Young, HA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,FREDERICK,MD 21702, USA. NR 26 TC 105 Z9 107 U1 3 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 1996 VL 16 IS 8 BP 563 EP 568 DI 10.1089/jir.1996.16.563 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA VE551 UT WOS:A1996VE55100001 PM 8877725 ER PT J AU Fartasch, M Sindransky, E Elias, PM Ginns, EI Holleran, WM AF Fartasch, M Sindransky, E Elias, PM Ginns, EI Holleran, WM TI Ultrastructural diagnosis of type II Gaucher disease by its unique epidermal abnormalities SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV ERLANGEN NURNBERG,DEPT DERMATOL,D-8520 ERLANGEN,GERMANY. NIMH,SEC MOL NEUROGENET,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT DERMATOL,SAN FRANCISCO,CA 94143. VET ADM MED CTR,DERMATOL SERV,SAN FRANCISCO,CA 94121. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 1996 VL 107 IS 2 BP 14 EP 14 PG 1 WC Dermatology SC Dermatology GA UY642 UT WOS:A1996UY64200038 ER PT J AU Leonard, WJ AF Leonard, WJ TI Dysfunctional cytokine receptor signaling in severe combined immunodeficiency SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article ID GAMMA-CHAIN GENE; JAK-3 JANUS KINASE; MICE LACKING JAK3; IL-2 RECEPTOR; BETA-CHAIN; LYMPHOID DEVELOPMENT; T-CELLS; INTERLEUKIN-7 RECEPTOR; FUNCTIONAL COMPONENT; CYTOPLASMIC DOMAINS RP Leonard, WJ (reprint author), NHLBI,NIH,LAB MOL IMMUNOL,BETHESDA,MD 20892, USA. NR 66 TC 22 Z9 22 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD AUG PY 1996 VL 44 IS 6 BP 304 EP 311 PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE506 UT WOS:A1996VE50600002 PM 8795294 ER PT J AU Nelson, VC AF Nelson, VC TI Synthesis of isotopically labelled DNA degradation products for use in mass spectrometric studies of cellular DNA damage SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE DNA; mass spectrometry; carcinogenesis ID QUANTITATIVE-DETERMINATION; BASES AB Thirteen substituted purines and pyrimidines bearing from three to five carbon, nitrogen and/or deuterium isotopic labels have been synthesized in yields ranging from .1 to 70%. Most of the products originate from the same small number of commercially available labelled starting materials, and in several cases one intermediate leads to two products, thus minimizing the expense and time required. The parent compounds are found in tissue as the result of DNA damage often linked with carcinogenesis and mutagenesis. The synthesized compounds serve as internal standards for the study of DNA damage using mass spectrometry. RP Nelson, VC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,POB B,FREDERICK,MD 21702, USA. NR 25 TC 24 Z9 24 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD AUG PY 1996 VL 38 IS 8 BP 713 EP 723 DI 10.1002/(SICI)1099-1344(199608)38:8<713::AID-JLCR886>3.0.CO;2-I PG 11 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA UZ480 UT WOS:A1996UZ48000002 ER PT J AU Vodovotz, Y Letterio, JJ Geiser, AG Chesler, L Roberts, AB Sparrow, J AF Vodovotz, Y Letterio, JJ Geiser, AG Chesler, L Roberts, AB Sparrow, J TI Control of nitric oxide production by endogenous TGF-beta(1) and systemic nitric oxide in retinal pigment epithelial cells and peritoneal macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE retinal pigment epithelial cells; interferon-gamma; lipopolysaccharide ID TRANSFORMING GROWTH-FACTOR; GROWTH-FACTOR-BETA-1 NULL MICE; SYNTHASE MESSENGER-RNA; SMOOTH-MUSCLE CELLS; FACTOR-BETA; MOUSE MACROPHAGES; IFN-GAMMA; TGF-BETA; MURINE MACROPHAGES; INTERFERON-GAMMA AB Both in vivo and in vitro experiments demonstrate that transforming growth factor-beta(1) (TGF-beta(1)) suppresses expression of the inducible form of nitric oxide synthase (iNOS), In this study, we examined the effects of exogenous and endogenous TGF-beta(1) on retinal pigment epithelial (RPE) cells and resident peritoneal macrophages ex vivo using cells from TGF-beta(1) null (TGF-beta(1)(-/-)) mice or age-matched wild-type (TGF-beta(1)(+/+)) or heterozygous (TGF-beta(1)(+/-)) littermates. RPE cells from both TGF-beta(1)(+/-) mice and TGF-beta(1)(+/+) littermates produced NO and were immunocytochemically positive for iNOS protein only following treatment with interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS); however, RPE cells from TGF-beta(1)(-/-) mice produced 40% more NO than cells from TGF-beta(1)(+/+) mice, In contrast, resident peritoneal macrophages from both TGF-beta(1)(+/+) and TGF-beta(1)(-/-) mice expressed iNOS protein without stimulation and in the absence of detectable production of NO, The expression of iNOS was increased by treatment with IFN-gamma, resulting in detectable levels of NO, Macrophages from TGF-beta(1)(+/+) mice appeared to produce NO in a manner inversely proportional to the serum content of NO2- and NO3- of the mice from which the cells were obtained; no such correlation existed in TGF-beta(1)(+/-) or TGF-beta(1)(-/-) mice, Treatment of RPE cells or macrophages from both TGF-beta(1)(+/+) and TGF-beta(1)(-/-) mice with exogenous TGF-beta(1) decreased both iNOS protein and NO production, These findings demonstrate a novel role of endogenous TGF-beta(1) in coupling systemic NO production to the production of NO by macrophages, and demonstrate that endogenous and exogenous TGF-beta(1) can act differently to suppress NO production. C1 NIH,CHEMOPREVENT LAB,BETHESDA,MD 20892. NEW YORK HOSP,CORNELL MED CTR,DEPT OPHTHALMOL,MARGARET M DYSON VIS RES INST,NEW YORK,NY 10021. NR 47 TC 23 Z9 23 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 1996 VL 60 IS 2 BP 261 EP 270 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA VE500 UT WOS:A1996VE50000014 PM 8773588 ER PT J AU Chen, F SLife, L Kishida, T Mulvihill, J Tisherman, SE Zbar, B AF Chen, F SLife, L Kishida, T Mulvihill, J Tisherman, SE Zbar, B TI Genotype-phenotype correlation in vonHippel-Lindau disease: Identification of a mutation associated with VHL type 2A SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE vonHippel-Lindau disease; genotype-phenotype correlation; VHL type 2A ID TUMOR-SUPPRESSOR GENE; SOMATIC MUTATIONS; PHEOCHROMOCYTOMA; CARCINOMA; ALLELE; LOCUS AB A family with von Hippel-Lindau disease (VHL) type 2A has been shown to have a T to C missense mutation at nucleotide 547 of the VHL gene. This gives further support for the proposal to associate the 547 T to C mutation with phenotype VHL 2A. C1 NCI, FREDERICK CANC RES & DEV CTR, IMMUNOBIOL LAB, FREDERICK, MD 21702 USA. SCI APPLICAT INT CORP, FREDERICK, MD 21702 USA. UNIV PITTSBURGH, SCH MED, DEPT HUMAN GENET, PITTSBURGH, PA USA. NR 14 TC 42 Z9 42 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD AUG PY 1996 VL 33 IS 8 BP 716 EP 717 DI 10.1136/jmg.33.8.716 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA VB662 UT WOS:A1996VB66200019 PM 8863170 ER PT J AU Perfetti, R Raygada, M Wang, Y Zenilman, ME Egan, JM Denno, KM Sadler, TW Shuldiner, AR AF Perfetti, R Raygada, M Wang, Y Zenilman, ME Egan, JM Denno, KM Sadler, TW Shuldiner, AR TI Regenerating (reg) and insulin genes are expressed in prepancreatic mouse embryos SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID PANCREATIC THREAD PROTEIN; STONE PROTEIN; NUCLEOTIDE-SEQUENCE; MESSENGER-RNA; ACID; AMELIORATION; TISSUES; CDNA; RATS AB The pancreatic regenerating (reg) gene is proposed to be involved in pancreatic beta-cell growth. Up- or down-regulation of reg gene expression has been shown to parallel variations in beta-cell mass and function in the adult pancreas. In several species at least two nonallelic reg genes have been identified. In this study we investigated the expression of each individual reg gene (reg-I and reg-II) during embryogenesis in the mouse. Single mouse embryos were harvested at 8.5, 9, 10, and 12 days of development, homogenized and subjected individually to reverse transcription (RT)-PCR, with a single primer pair to amplify both reg-I and -II mRNAs. Southern blot analysis of the RT-PCR products revealed the presence of reg mRNA at day 9 of embryogenesis, just before the beginning of pancreatic organogenesis. Slot-blot analysis with internal oligonucleotide probes that specifically recognize reg-I or -II sequences demonstrated that only reg-I mRNA was present in day 9 and day 10 prepancreatic embryos. Reg-II mRNA was not detected until day 12, a stage corresponding to late organogenesis. RT-PCR for insulin mRNA from the same samples used for the amplification of reg mRNA showed that the earliest insulin expression occurred at day 8.5, and coincided with the onset of reg-I expression. Hybridization with gene-specific oligonucleotide probes revealed that only insulin-II mRNA was detectable at this time. Insulin-I mRNA was not detectable until day 12 and coincided with early reg-II expression. These results suggest that the two nonallelic reg genes and the two insulin genes are expressed differentially during early embryogenesis. Differential expression of reg-I and -II suggests that they may be induced by different and independent stimuli and have distinct functions. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21224. UNIV N CAROLINA,BIRTH DEFECTS CTR,CHAPEL HILL,NC 27599. RP Perfetti, R (reprint author), NIA,GERONTOL RES CTR,LCP,NIH,DIABET UNIT,RM 2B02,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NICHD NIH HHS [HD19593] NR 30 TC 10 Z9 11 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD AUG PY 1996 VL 17 IS 1 BP 79 EP 88 DI 10.1677/jme.0.0170079 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VC652 UT WOS:A1996VC65200010 PM 8863190 ER PT J AU Shapiro, BA Kasprzak, W AF Shapiro, BA Kasprzak, W TI STRUCTURELAB: A heterogeneous bioinformatics system for RNA structure analysis SO JOURNAL OF MOLECULAR GRAPHICS & MODELLING LA English DT Article ID SECONDARY STRUCTURE PREDICTION; INFORMATION; PSEUDOKNOTS; ALGORITHM; SEQUENCE; PROTEIN AB STRUCTURELAB is a computational system that has been developed to permit the use of a broad array of approaches for the analysis of the structure of RNA. The goal of the development is to provide a large set of reals that cart be well integrated with experimental biology to aid in the process of the determination of the underlying structure of RNA sequences. The approach taken views the structure determination problem as one of dealing with a database of many computationally generated structure es and provides the capability to analyze this data set from different perspectives. Many algorithms are integrated into one system that also utilizes a heterogeneous computing approach permitting the use of several computer architectures to help solve the posed problems. These different computational platforms make it relatively easy to incorporate currently existing programs as well as newly developed algorithms and to best match these algorithms to the appropriate hardware. The system has been written in Common Lisp running on SUN ol SCI Unix workstations, and it utilizes a network of participating machines defined in reconfigurable tables. A window-based interface makes this heterogeneous environment as transparent to the user as possible. (C) 1996 by Elsevier Science Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERIC BIOMED SUPERCOMP CTR,SAIC FREDERICK,FREDERICK,MD 21702. RP Shapiro, BA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MATH BIOL LAB,IMAGE PROC SECT,DIV BASIC SCI,NIH,BLDG 469,FREDERICK,MD 21702, USA. NR 26 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1093-3263 J9 J MOL GRAPH MODEL JI J. Mol. Graph. PD AUG PY 1996 VL 14 IS 4 BP 194 EP & DI 10.1016/S0263-7855(96)00063-X PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA WN390 UT WOS:A1996WN39000002 PM 9076633 ER PT J AU Mossakowska, M Korn, ED AF Mossakowska, M Korn, ED TI Ca2+ bound to the high affinity divalent cation-binding site of actin enhances actophorin-induced depolymerization of muscle F-actin but inhibits actophorin-induced depolymerization of Acanthamoeba F-actin SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article ID STRUCTURAL DYNAMICS; CASTELLANII; POLYMERIZATION; PROTEIN AB The cation tightly bound to actin, Mg2+ or Ca2+, affects the ability of actophorin to accelerate depolymerization of filaments and bind to monomers of actin prepared from rabbit skeletal muscle and Acanthamoeba castellanii. Actophorin interacted similarly with muscle and Acanthamoeba Mg2+-F-actin but depolymerized muscle Mg2+-F-actin more efficiently. Muscle Ca2+-F-actin depolymerized about 5 times more rapidly than Mg2+-F-actin in the presence of actophorin but Acanthamoeba Ca2+-F-actin was highly resistant to actophorin. Muscle actin subunits dissociated more rapidly than Acanthamoeba actin subunits from copolymers of muscle and Acanthamoeba Ca2+-actin upon addition of actophorin although Acanthamoeba actin dissociated much more rapidly from copolymers than from its homopolymer. The Kd of the 1:1 complex between actophorin and monomeric actin was somewhat lower for muscle Mg2+-ATP-G-actin than for both Acanthamoeba Mg2+-ATP-G-actin and muscle Ca2+-ATP-G-actin. The data for the interactions of actophorin with Acanthamoeba Ca2+-ATP-G-actin or muscle and amoeba Mg2+- and Ca2+-ADP-G-actin were incompatible with the formation of 1:1 actin:actophorin complexes and, thus, Kd values could not be calculated. While it may not be surprising that actophorin would interact differently with Mg2+- and Ca2+-actin, it is unexpected that the nature of the tightly bound cation would have such dramatically opposite effects on the ability of actophorin to depolymerize muscle and Acanthamoeba F-actin. Differential severing by actophorin, with Acanthamoeba Ca2+-actin being almost totally resistant, is sufficient to explain the results but other possibilities cannot be ruled out. C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012 NR 16 TC 9 Z9 9 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD AUG PY 1996 VL 17 IS 4 BP 383 EP 389 DI 10.1007/BF00123355 PG 7 WC Cell Biology SC Cell Biology GA VH329 UT WOS:A1996VH32900001 PM 8884594 ER PT J AU Bernart, MW Cardellina, JH Balaschak, MS Alexander, MR Shoemaker, RH Boyd, MR AF Bernart, MW Cardellina, JH Balaschak, MS Alexander, MR Shoemaker, RH Boyd, MR TI Cytotoxic falcarinol oxylipins from Dendropanax arboreus SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ABSOLUTE-CONFIGURATION; PANAX-GINSENG; POLYACETYLENE COMPOUNDS; UMBELLIFEROUS PLANTS; CONSTITUENTS; STEREOCHEMISTRY; DIACETYLENE; COMPONENTS; CANCER; ROOTS AB The crude organic extract of Dendropanax arboreus was selected as a candidate for bioassay-guided fractionation on the basis of its relatively selective cytotoxicity to a subset of cell lines within the National Cancer Institute's disease-oriented in vitro tumor-screening panel. The major compound responsible for the in vitro cytotoxicity was falcarinol (1). Several other known compounds were isolated and found to be cytotoxic, including dehydrofalcarinol (2), a diynene (3), falcarindiol (4), and dehydrofalcarindiol (5). In addition, two novel polyacetylenes, dendroarboreols A (6) and B (7), were isolated and characterized by standard and inverse-detected NMR methods. Compounds were selected from this series for absolute stereochemical determination using the modified Mosher method and preliminary in vivo evaluation using a LOX melanoma mouse xenograft model. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. NR 39 TC 90 Z9 95 U1 1 U2 16 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD AUG PY 1996 VL 59 IS 8 BP 748 EP 753 DI 10.1021/np960224o PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA VE379 UT WOS:A1996VE37900007 PM 8792622 ER PT J AU McKee, TC Fuller, RW Covington, CD Cardellina, JH Gulakowski, RJ Krepps, BL McMahon, JB Boyd, MR AF McKee, TC Fuller, RW Covington, CD Cardellina, JH Gulakowski, RJ Krepps, BL McMahon, JB Boyd, MR TI New pyranocoumarins isolated from Calophyllum lanigerum and Calophyllum teysmannii SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID RAIN-FOREST TREE; NATURAL-PRODUCTS; MOSHER METHOD; COUMARINS AB During a chemotaxonomic survey of Calophyllum extracts present in the National Cancer Institute's natural product repository, four new pyranocoumarins were isolated from extracts of C. lanigerum var. austrocoriaceum and C. teysmannii var. inophylloide (King.) P. F. Stevens (Clusiaceae). The structure elucidation and anti-HIV activity of calanolide E2 (4), cordatolide E (5), pseudocordatolide C (6), and calanolide F (9), along with a simple prenylated coumarin precursor (11), are described here. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. NR 14 TC 87 Z9 92 U1 0 U2 1 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD AUG PY 1996 VL 59 IS 8 BP 754 EP 758 DI 10.1021/np9603784 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA VE379 UT WOS:A1996VE37900008 PM 8792623 ER PT J AU Jones, TH Torres, JA Snelling, RR Spande, TF AF Jones, TH Torres, JA Snelling, RR Spande, TF TI Primary tetradecenyl amines from the ant Monomorium floricola SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID VENOM CHEMISTRY AB In contrast to other ants in the genus Monomorium that produce cyclic amines, extracts of Monomorium floricola contain (Z)-7-tetradecenylamine (1) and (Z)-9-tetradecenylamine (2). The structures of these compounds were established from their spectral data and by comparison with synthetic 2. C1 UNIV PUERTO RICO,DEPT BIOL,SAN JUAN,PR 00931. US FOREST SERV,IITF,RIO PIEDRAS,PR 00928. LOS ANGLES CTY MUSEUM NAT HIST,LOS ANGELES,CA 90007. NIDDK,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. RP Jones, TH (reprint author), VIRGINIA MIL INST,DEPT CHEM,LEXINGTON,VA 24450, USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD AUG PY 1996 VL 59 IS 8 BP 801 EP 802 DI 10.1021/np960350s PG 2 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA VE379 UT WOS:A1996VE37900021 PM 8792628 ER PT J AU Liang, BC AF Liang, BC TI Effects of hypoxia on drug resistance phenotype and genotype in human glioma cell lines SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE glioblastoma; BCNU; cis-platinum; drug therapy ID HAMSTER OVARY CELLS; MULTIDRUG-RESISTANCE; BRAIN-TUMORS; GENE; EXPRESSION; ERCC1; METHYLTRANSFERASE; REOXYGENATION; AMPLIFICATION; DENITROSATION AB Recurrent gliomas are most often treated by chemotherapy. However, these tumors typically acquire resistance to most drugs administered, and patients will usually die of recurrent tumor. Factors which may play a role include overexpression of putative multidrug resistance genes, such as the multidrug resistance gene 1 (MDR1), multidrug resistance associated protein gene (MRP), 06-alkylguanine, DNA alkyltransferase gene (06MT) and excision repair cross complementing gene 1 (ERCC1). Tumor hypoxia has also been shown to be associated with drug resistance in other soft tissue tumors. Since gliomas have regions of diminished oxygenation, and have clinical resistance to chemotherapy, the relationship between phenotypic resistance to chemotherapy after hypoxic exposure and expression of drug resistance genes was investigated in glioma cell lines (U373 MG, PFAT-MT). After a 24 hour exposure to hypoxia, drugs 1, 3-bis, 2-chloroethyl-1-nitrosurea (BCNU) and cis-diammine, dichloroplatinum II (CDDP) were administered, and cell survival was determined. Hypoxic exposure was associated with increased survival of the cell lines after administration of BCNU and CDDP, with resistance to BCNU 15 to 30-fold when compared to cells which did not undergo hypoxic exposure. Both tumor cell lines also showed some degree of resistance to CDDP, although not to the extent of BCNU (2 to 3-fold increased resistance). The expression of the drug resistance genes was found to be unchanged when comparing cells which had undergone hypoxic exposure and those which had not. Thus, hypoxic exposure is associated with substantial drug resistance in brain tumor cell lines. The lack of correlation between the induced phenotype and known drug resistance genes suggests other mechanisms may be acting in these tumors in hypoxic conditions. C1 NCI,CLIN PHARMACOL BRANCH,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NR 41 TC 78 Z9 79 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD AUG PY 1996 VL 29 IS 2 BP 149 EP 155 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA VB118 UT WOS:A1996VB11800005 PM 8858520 ER PT J AU Yakovchenko, E Whalin, M Movsesyan, V Guroff, G AF Yakovchenko, E Whalin, M Movsesyan, V Guroff, G TI Insulin-like growth factor I receptor expression and function in nerve growth factor - Differentiated PC12 cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PC12; insulin-like growth factor; nerve growth factor ID PHEOCHROMOCYTOMA CELLS; BRAIN; PROLIFERATION; LINE AB Receptors for insulin-like growth factor I (IGF-I) were studied on PC12EY cells, a subclone of PC12. Differentiation of PC12EY cells with nerve growth factor (NGF) did not alter either the number of IGF-I receptors nor their affinity for IGF-I. IGF-I receptors remained fully functional during differentiation, promoting increases in thymidine incorporation, glucose uptake, amino acid uptake, and the phosphorylation of the S6 protein of the ribosomes. IGF-I also increased the proportion of differentiated cells found in S-phase. But although the addition of IGF-I to naive cells caused an increase in cell number, there was no comparable increase when IGF-I was added to differentiated cells. Thus, although the receptor for IGF-I continues to be present and functional, IGF-I fails to induce cell proliferation in differentiated PC12 cells. C1 NICHHD, GROWTH FACTORS SECT, BETHESDA, MD 20892 USA. NR 31 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1996 VL 67 IS 2 BP 540 EP 548 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UX585 UT WOS:A1996UX58500011 PM 8764578 ER PT J AU Sheu, KFR Calingasan, NY Dienel, GA Baker, H Jung, EH Kim, KS Paoletti, F Gibson, GE AF Sheu, KFR Calingasan, NY Dienel, GA Baker, H Jung, EH Kim, KS Paoletti, F Gibson, GE TI Regional reductions of transketolase in thiamine-deficient rat brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE immunocytochemistry; in situ hybridization; metabolic encephalopathy; thiamine deficiency; transketolase; thiamine pyrophosphate; Wernicke-Korsakoff syndrome ID WERNICKE-KORSAKOFF-SYNDROME; ALPHA-KETOGLUTARATE DEHYDROGENASE; 2 EXPERIMENTAL-MODELS; ALZHEIMERS-DISEASE; DEPENDENT ENZYMES; EXTRACELLULAR GLUTAMATE; ABNORMALITY; ENCEPHALOPATHY; FIBROBLASTS; PURIFICATION AB Thiamine deficiency impairs oxidative metabolism and causes metabolic encephalopathy. An early reduction in transketolase (TK) activity may be an important pathogenic event. To assess the role of TK, we have delineated the regional/cellular distribution of TK protein and mRNA in adult rat brain in pyrithiamine-induced thiamine deficiency. TK activity declined in both vulnerable and spared regions. Immunoblots showed a parallel reduction of TK protein. With a few exceptions, immunocytochemistry indicated an overall decline of TK immunoreactivity and the decrease was not specific to vulnerable areas. In contrast to the pronounced, general decline of TK protein, in situ hybridization revealed a regional decrease of 0-25% of TK mRNA in thiamine deficiency. Northern blots indicated a similar level of TK mRNA in whole brain in thiamine deficiency. These results show that the decline of TK activity results from a proportional decrease of TK protein, and the deficiency may be due to an instability of TK protein or an inhibition of TK mRNA translation. The lack of correlation of the distribution, and the absence of specific alteration, of TK in affected regions suggest that the reduced TK may not be linked directly to selective vulnerability in thiamine deficiency. C1 CORNELL UNIV,COLL MED,BURKE MED RES INST,WHITE PLAINS,NY 10605. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. UNIV FLORENCE,IST PATOL GEN,FLORENCE,ITALY. FU NIAAA NIH HHS [AA 08246]; NIMH NIH HHS [MH-48325] NR 39 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1996 VL 67 IS 2 BP 684 EP 691 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UX585 UT WOS:A1996UX58500029 PM 8764596 ER PT J AU Jones, CR Arai, T Bell, JM Rapoport, SI AF Jones, CR Arai, T Bell, JM Rapoport, SI TI Preferential in vivo incorporation of [H-3]arachidonic acid from blood into rat brain synaptosomal fractions before and after cholinergic stimulation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE arachidonic acid; cholinergic; synapse; fatty acid model; functional activity; brain; phospholipids ID RECEPTOR-MEDIATED ACTIVATION; SYNAPTIC PLASMA-MEMBRANES; ARACHIDONIC-ACID; SIGNAL TRANSDUCTION; FATTY-ACIDS; UNANESTHETIZED RATS; CEREBRAL-CORTEX; 2ND MESSENGERS; PHOSPHOLIPASE-A2; BINDING AB Awake adult male rats were infused intravenously with [H-3]arachidonic acid for 5 min, with or without prior administration of an M1 cholinergic agonist, arecoline (15 mg/kg i.p.). Methylatropine was also administered (4 mg/kg s.c.) to control and arecoline-treated animals, At 15 min postinfusion, the animals were killed, brains were removed and frozen, and subcellular fractions were obtained from homogenates of whole brain, Total radioactivity and radioactivity in various lipid classes were determined for each fraction following normalization for exposure by use of a unidirectional incorporation coefficient, k*(brain). In control animals, incorporation was greatest in synaptosomal and microsomal fractions, accounting for 50 and 30% of total label incorporated into membrane lipids, respectively, Arecoline increased incorporation in these two fractions by up to 400% but did not increase incorporation into the myelin, mitochondrial, or cytosolic fractions. Of the incorporated radioactivity, 50-80% was in phospholipid in microsomal and synaptosomal fractions, indicating that phospholipid is the major lipid affected by cholinergic stimulation, These results demonstrate that plasma [H-3]arachidonic acid is preferentially incorporated into phospholipids of synaptosomal and microsomal fractions of rat brain. Cholinergic stimulation increases incorporation into these fractions, likely by activation of phospholipase A(2) and/or C in association with acyltransferase activity. Thus, intravenously infused radiolabeled arachidonic acid can be used to examine synapse-mediated changes in brain phospholipid metabolism in vivo. RP NIA, NEUROSCI LAB,NIH,BLDG 10,ROOM 6C103,10 CTR DR, MSC 1582, BETHESDA, MD 20892 USA. NR 45 TC 48 Z9 48 U1 0 U2 0 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1996 VL 67 IS 2 BP 822 EP 829 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UX585 UT WOS:A1996UX58500045 PM 8764612 ER PT J AU Calogero, AE Scaccianoce, S Burrello, N Nicolai, R Muscolo, LAA Kling, MA Angelucci, L DAgata, R AF Calogero, AE Scaccianoce, S Burrello, N Nicolai, R Muscolo, LAA Kling, MA Angelucci, L DAgata, R TI The Kappa-opioid receptor agonist MR-2034 stimulates the rat hypothalamic-pituitary-adrenal axis: Studies in vivo and in vitro SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE kappa-opioid receptors; hypothalamic-pituitary-adrenal axis; corticotrophin-releasing hormone; ACTH; corticosterone; MR-2034; MR-1452 ID CORTICOTROPIN-RELEASING-FACTOR; HORMONE-SECRETION INVITRO; NALORPHINE-LIKE DRUGS; CHRONIC SPINAL DOG; ADRENOCORTICAL AXIS; HUMAN-BRAIN; IMMUNOREACTIVE DYNORPHIN; METHIONINE-ENKEPHALIN; SEROTONIN AGONISTS; OPIATE AGONISTS AB There is increasing evidence that opiates not only have analgesic properties, but also regulate mechanisms activated during the stress response, such as the hypothalamic-pituitary-adrenal (HPA) axis. Indeed, opioid-containing neurons innervate the paraventricular nucleus and the median eminence, thus modulating inputs to ACTH-controlling neurons. In addition, dynorphin (the endogenous ligand of the kappa-opioid receptor)-like peptides have been found co-localized with corticotrophin-releasing hormone (CRH) and are believed to be co-secreted with it in the hypophyseal portal circulation to modulate ACTH release, In this study, we evaluated the effects of the selective kappa-opioid receptor agonist MR-2034 [(-)-N-(2-tetrahydrofurfuryl)-normetazocine] on the HPA axis in vivo and in vitro. MR-2034 was given intravenously to catheterized, freely moving, male Sprague-Dawley rats and serial blood samples were collected for ACTH and corticosterone (B) measurements, We evaluated also the site of MR-2034 action on the HPA axis in vivo, after the administration of alpha-helical CRH(9-41), a CRH receptor antagonist, on hypothalamic CRH, pituitary ACTH, and B release in vitro, MR-2034 increased plasma ACTH and B levels in a dose-related fashion and this effect was antagonized by the selective kappa-opioid receptor antagonist MR-1452. In the presence of alpha-helical CRH(9-41), the responses of plasma ACTH and B to MR-2034 were blunted significantly, suggesting that this compound activates the HPA axis through a CRH-dependent mechanism. Accordingly, MR-2034 stimulated hypothalamic CRH release in vitro in a concentration-dependent fashion and this effect was antagonized dose-dependently by MR-1452. However, the stimulatory effect of MR-2034 on plasma ACTH and B in vivo was not completely abolished by alpha-helical CRH(9-41), suggesting that an additional, CRH-independent, mechanism was involved, Indeed, MR-2034 was able to stimulate basal ACTH output in a dose-dependent manner and this effect was antagonized by MR-1452 in vitro, On the other hand, MR-2034 did not have any effect on B release from adrenocortical cells or adrenal quarters in vitro. These results show that the benzomorphan MR-2034 stimulates the HPA axis in the rat by acting at the hypothalamic and the pituitary level. We hypothesize that endogenous kappa-opioid peptides not only act at the pituitary level to increase ACTH output, but may also act at the hypothalamic level to increase CRH release through an autocrine and/or ultrashort positive feedback mechanism. C1 UNIV CATANIA,SCH MED,DEPT INTERNAL MED 1,CHAIR ANDROL,CATANIA,ITALY. UNIV ROMA LA SAPIENZA,INST PHARMACOL,CHAIR 2,ROME,ITALY. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 44 TC 34 Z9 34 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD AUG PY 1996 VL 8 IS 8 BP 579 EP 585 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA VC541 UT WOS:A1996VC54100002 PM 8866244 ER PT J AU Gawne, TJ Kjaer, TW Richmond, BJ AF Gawne, TJ Kjaer, TW Richmond, BJ TI Latency: Another potential code for feature binding in striate cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VISUAL-CORTEX; CAT; ORIENTATION; CONTRAST; PRIMATE; MONKEY; OSCILLATIONS; SUMMATION; NEURONS; CELLS AB 1. We recorded the responses of 37 striate cortical complex cells in fixating monkeys while presenting a set of oriented stimuli that varied in contrast. 2. The two response parameters of strength and latency can be interpreted as a code: the strength defines the stimulus form (here the orientation), and the latency is more a function of the stimulus contrast. 3. Synchronization based on latency could make a strong contribution to the process of organizing the neural responses to different objects, i.e., binding. RP Gawne, TJ (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,RM 1B80,BETHESDA,MD 20892, USA. NR 14 TC 245 Z9 245 U1 2 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1996 VL 76 IS 2 BP 1356 EP 1360 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VD972 UT WOS:A1996VD97200055 PM 8871243 ER PT J AU Mattay, VS Berman, KF Ostrem, JL Esposito, G VanHorn, JD Bigelow, LB Weinberger, DR AF Mattay, VS Berman, KF Ostrem, JL Esposito, G VanHorn, JD Bigelow, LB Weinberger, DR TI Dextroamphetamine enhances ''neural network-specific'' physiological signals: A positron-emission tomography rCBF study SO JOURNAL OF NEUROSCIENCE LA English DT Article DE dextroamphetamine; rCBF; PET; monoamines; dopamine; working memory; hippocampus; dorsolateral prefrontal cortex ID DORSOLATERAL PREFRONTAL CORTEX; CEREBRAL BLOOD-FLOW; LOCUS COERULEUS STIMULATION; D-AMPHETAMINE; NEURONAL-ACTIVITY; RAT HIPPOCAMPUS; SCHIZOPHRENIA; DYSFUNCTION; DOPAMINE; NOREPINEPHRINE AB Previous studies in animals and humans suggest that monoamines enhance behavior-evoked neural activity relative to nonspecific background activity (i.e., increase signal-to-noise ratio). We studied the effects of dextroamphetamine, an indirect monoaminergic agonist, on cognitively evoked neural activity in eight healthy subjects using positron-emission tomography and the O-15 water intravenous bolus method to measure regional cerebral blood flow (rCBF). Dextroamphetamine (0.25 mg/kg) or placebo was administered in a double-blind, counterbalanced design 2 hr before the rCBF study in sessions separated by 1-2 weeks. rCBF was measured while subjects performed four different tasks: two abstract reasoning tasks-the Wisconsin Card Sorting Task (WCST), a neuropsychological test linked to a cortical network involving dorsolateral prefrontal cortex and other association cortices, and Ravens Progressive Matrices (RPM), a nonverbal intelligence test linked to posterior cortical systems-and two corresponding sensorimotor control tasks, There were no significant drug or task effects on pCO(2) or on global blood flow. However, the effect of dextroamphetamine (i.e., dextroamphetamine vs placebo) on task-dependent rCBF activation (i.e., task-control task) showed double dissociations with respect to task and region in the very brain areas that most distinctly differentiate the tasks, In the superior portion of the left inferior frontal gyrus, dextroamphetamine increased rCBF during WCST but decreased it during RPM (ANOVA F-(1,F-7) = 16.72, p < 0.0046). In right hippocampus, blood WOW decreased during WCST but increased during RPM (ANOVA F-(1,F-7) = 18.7, p < 0.0035), These findings illustrate that dextroamphetamine tends to ''focus'' neural activity, to highlight the neural network that is specific for a particular cognitive task. This capacity of dextroamphetamine to induce cognitively specific signal augmentation may provide a neurobiological explanation for improved cognitive efficiency with dextroamphetamine. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 72 TC 120 Z9 120 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 1996 VL 16 IS 15 BP 4816 EP 4822 PG 7 WC Neurosciences SC Neurosciences & Neurology GA UX955 UT WOS:A1996UX95500027 PM 8764668 ER PT J AU Farrer, RG Quarles, RH AF Farrer, RG Quarles, RH TI Extracellular matrix upregulates synthesis of glucosylceramide-based glycosphingolipids in primary Schwann cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE basement membrane; glycosphingolipids; matrigel; Schwann cells ID BASEMENT-MEMBRANE; BASAL LAMINA; GLYCOLIPID BIOSYNTHESIS; BIOLOGICAL-ACTIVITY; AXONAL REGULATION; MYELIN FORMATION; MELANOMA-CELLS; DIFFERENTIATION; EXPRESSION; INHIBITOR AB The formation of basement membrane around Schwann cells that are in contact with axons is necessary for Schwann cell differentiation and myelin formation in the peripheral nervous system, However, primary Schwann cells grown on basement membrane in the absence of neuronal influence show increased proliferation rather than differentiation, which implies that the signals generated by Schwann cell-basement membrane interactions are multipotential, We examined the effect of matrigel, an exogenous basement membrane preparation, and other extracellular matrix growth surfaces on primary Schwann cells to determine if the resulting interactions play a role in the control of glycosphingolipid synthesis, Isolated primary Schwann cells grown on a thin layer of matrigel rapidly adhered to the surface and exhibited a greater degree of cell spreading when compared to cells grown on the nonspecific substrate polylysine. Labeling of the cells with [H-3]galactose between 24 and 48 hr after plating revealed that the incorporation of [H-3]galactose into glucosylceramide-based glycosphingolipids increased from 1.5-3-fold on matrigel in comparison to cells grown on polylysine. The major labeled glycolipids under both conditions were GM3 ganglioside and two neutral glycolipids that comigrated with GbOse(4)Cer (GalNAc beta 1-3Gal alpha 1-4Gal beta 1-1Cer) and GbOse(5)Cer (GalNAc alpha 1-3Gal-NAc beta 1-3Gal alpha 1 -4Gal beta 1-4Glc beta 1-1Cer) standards. There was little or no increase in the incorporation of [H-3]leucine, [H-3]galactose, or [H-3]glucosamine into proteins or [H-3]palmitic acid into phospholipids, free ceramides, or sphingomyelin, suggesting that the matrigel-induced increase in the synthesis of the glycolipids was selective, In the absence of serum, there was little or no difference in the levels of glycolipid labeling between cells grown on the two substrata, demonstrating that serum factors were required for matrigel to have this effect, When cells were grown on surfaces coated with individual extracellular matrix components, those cells grown on laminin and collagen IV showed an increase in glycolipid labeling similar to that produced by matrigel, while labeling increased to a lesser degree for the other components tested, Thus, the signals generated by interactions between Schwann cells and basement membrane, particularly the laminin and collagen IV constituents, contribute to the regulation of glycolipid synthesis which in turn may affect cell morphology and proliferation. (C) 1996 Wiley-Liss, Inc.* RP Farrer, RG (reprint author), NINCDS,MYELIN & BRAIN DEV SECT,CELLULAR & MOL NEUROBIOL LAB,NIH,BLDG 49,ROOM 2A28,49 CONVENT DR,BETHESDA,MD 20892, USA. NR 46 TC 2 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 1 PY 1996 VL 45 IS 3 BP 248 EP 257 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UZ735 UT WOS:A1996UZ73500006 PM 8841985 ER PT J AU Black, RJ Rausch, DM AF Black, RJ Rausch, DM TI NeuroAIDS, current understanding and future directions SO JOURNAL OF NEUROVIROLOGY LA English DT Editorial Material C1 NIMH,OFF AIDS,NIH,ROCKVILLE,MD 20857. NIAID,NIH,ROCKVILLE,MD 20857. NR 0 TC 7 Z9 7 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 1996 VL 2 IS 4 BP 230 EP 233 DI 10.3109/13550289609146885 PG 4 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA VH076 UT WOS:A1996VH07600002 PM 8799213 ER PT J AU Agostini, HT Ryschkewitsch, CF Singer, EJ Stoner, GL AF Agostini, HT Ryschkewitsch, CF Singer, EJ Stoner, GL TI Co-infection with two JC virus genotypes in brain, cerebrospinal fluid or urinary tract detected by direct cycle sequencing of PCR products SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE AIDS; polyomavirus; progressive multifocal leukoencephalopathy; recombination; urine; viral evolution ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; BK-VIRUS; POLYOMAVIRUS; VARIANTS; EXCRETION; DISEASE; PATIENT; GENOME; AIDS AB The human polyomavirus TC (TCV), which exists in different geographically based genotypes, causes the central demyelinating disease known as progressive multifocal leukoencephalopathy (PML). A coding region recombinant ICV Type 1/Type 3 (Type 4) is excreted in the urine of some 16% of individuals in the USA. In addition, occasional 'crossovers' in viral DNA sequence at type-specific sites in the coding region occur between TCV genotypes amplified from PML brain. For recombination to occur requires the existence of two different genotypes in the same host. Here we provide evidence from direct cycle sequencing of PCR products that different genotypes of TCV can be found in a single tissue sample. After non-type-specific PCR amplification, cycle sequencing produced 'split bands' at type determining sites which were resolved into type or subtype-specific sequences by subcloning of the PCR products, PCR products with split bands at typing sites were found in two brain samples and in one cerebrospinal fluid (CSF) from AIDS patients with PML and in the urine of four immunocompetent individuals. This indicates that co-infection with two viral types does not depend on severe immunocompromise. Combinations of genotypes found were Types 1A & 1B, 1A & 2, 1B & 2 and 2 & 3. In one doubly infected patient the major TCV type excreted in the urine changed within 1 week. C1 NINCDS,EXPT NEUROPATHOL LAB,NIH,BETHESDA,MD 20892. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. NR 25 TC 27 Z9 27 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 1996 VL 2 IS 4 BP 259 EP 267 DI 10.3109/13550289609146889 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA VH076 UT WOS:A1996VH07600006 PM 8799217 ER PT J AU Chakrabarti, MC Le, N Paik, CH DeGraff, WG Carrasquillo, JA AF Chakrabarti, MC Le, N Paik, CH DeGraff, WG Carrasquillo, JA TI Prevention of radiolysis of monoclonal antibody during labeling SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE monoclonal antibody; labeling damage; immunoreactivity; yttrium-90; radioimmunotherapy; radiolysis ID B-CELL LYMPHOMA; RADIOLABELED-ANTIBODY; RADIOIMMUNOTHERAPY; AUTORADIOLYSIS; RADIONUCLIDES; ANTIGEN; Y-90 AB Monoclonal antibody may undergo loss of immunoreactivity due to radiation damage when labeled with large amounts of I-131 or Y-90 for therapy. Our aim was to develop a method to protect an antibody during the labeling procedure. Methods: As a model we used T101, a murine monoclonal antibody directed against CD5 antigen. Iodine-125-T101 (100 micrograms, 1 ml) was mixed with Y-90-DTPA (0.64MBq to 165.9MBq) for 24hr in order to deliver doses of 5Gy to 1280Gy to the solution. In separate experiments, I-125-T101 solutions were irradiated with Co-60 external beam delivering radiation doses of 40Gy to 1280Gy. The effect of radiation on T101 immunoreactivity was tested by using the CCRF-CEM cell line, and the bound T101 radioactivity was determined. In a final experiment, we directly labeled a DTPA conjugated T101 using 561MBq of Y-90 under conditions delivering approximately 640Gy to the solution. Previously used radioprotectants including human serum albumin, cysteamine and glycerol were evaluated. We focused on ascorbic acid because it is an FDA approved drug that does not interfere with the radiolabeling process. Results: The immunoreactivity of I-125-T101 was approximately 83 percent, but at 640Gy the immunoreactivity decrease to 7 percent. In contrast, in the presence of radioprotectants this decrease could be abrogated. External irradiation also showed a dose dependent decrease in immunoreactivity to as low as 0.3 percent at 1280Gy. Adding ascorbic acid (5.5mg/ml) to the solutions prior to the irradiation largely abrogated this decrease. The immunoreactivity of T101 labeled with Y-90 without protectant showed 46 percent immunoreactivity whereas, in presence of ascorbic acid (11mg/ml) full retention of immunoreactivity was observed. Conclusion: Various radioprotectants can successfully prevent the loss of immunoreactivity or breakdown as a result of radiolysis. Ascorbic acid is an effective radioprotectant that can be used to prevent loss of antibody immunoreactivity during the labeling process. C1 NCI,DEPT NUCL MED,WARREN G MAGNUSON CLIN CTR,NIH,BETHESDA,MD 20892. NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 22 TC 48 Z9 53 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1996 VL 37 IS 8 BP 1384 EP 1388 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VA931 UT WOS:A1996VA93100031 PM 8708780 ER PT J AU Aloj, L Lang, LX Jagoda, E Neumann, RD Eckelman, WC AF Aloj, L Lang, LX Jagoda, E Neumann, RD Eckelman, WC TI Evaluation of human transferrin radiolabeled with N-succinimidyl 4-[fluorine-18](fluoromethyl) benzoate SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE transferrin; fluorine-18; gallium-67; neoplasms; iron metabolism ID RECEPTOR-MEDIATED ENDOCYTOSIS; CELL-SURFACE GLYCOPROTEIN; MACROMOLECULAR TRACER; VASCULAR-PERMEABILITY; GALLIUM-TRANSFERRIN; BINDING; GA-67; ENZYME; FE-59 AB Iron metabolism plays a key role in cell proliferation and survival in rapidly growing cancer cells, Uptake is mediated by the carrier protein transferrin. The increased need for iron has been used as a method to target tumors and there is well-documented evidence that certain tumors can be imaged with tracers such as Ga-67, that mimic transferrin-mediated iron uptake, To obtain a tracer that would be better able to quantitate transferrin kinetics and indirectly evaluate iron metabolism, we have labeled human transferrin with the positron emitter, F-18, with a one-step high-specific activity method developed in our laboratory. Methods: We measured the binding affinities of [F-18]diferric (holo-) and iron-free (apo-) transferrin on two human cell lines, We also compared cellular uptake of [F-18]holo-transferrin and [Ga-67]citrate in various conditions, and washout of label incorporated into cells, Results: The binding affinity of [F-18]holo-transferrin was found to be the same as that reported for [I-125]holo-transferrin. In our hands there was no significant difference in binding affinity between diferric holo-transferrin and iron-free apo-transferrin, [F-18]holo-transferrin uptake rapidly reaches a steady-state equilibrium between the intracellular and extracellular environment, while gallium accumulation linearly increases with time, [F-18]holo-transferrin is rapidly recycled out of the cell with similar kinetics to those reported for [I-125]holo-transferrin. Conclusion: [F-18]holo-transferrin displays the properties of native transferrin and appears suitable for quantitative evaluation of transferrin kinetics in vivo. C1 NIH,PET DEPT,CTR CLIN,BETHESDA,MD 20892. NR 25 TC 19 Z9 19 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 1996 VL 37 IS 8 BP 1408 EP 1412 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VA931 UT WOS:A1996VA93100036 PM 8708785 ER PT J AU Dionne, RA AF Dionne, RA TI Propofol: An alternative general anesthetic for outpatient oral surgery - Discussion SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material RP Dionne, RA (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD AUG PY 1996 VL 54 IS 8 BP 948 EP 948 DI 10.1016/S0278-2391(96)90388-2 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VC593 UT WOS:A1996VC59300004 ER PT J AU Carlson, L Ho, P Smith, M Reisch, J Weitman, S AF Carlson, L Ho, P Smith, M Reisch, J Weitman, S TI Pediatric phase I drug tolerance: A review and comparison of recent adult and pediatric phase I trials SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Review DE phase I trials; cancer chemotherapy; maximum tolerated dose ID 24-HOUR CONTINUOUS INFUSION; DICARBOXYLATE PLATINUM-II; MALIGNANT SOLID TUMORS; INDICINE N-OXIDE; CLINICAL-TRIAL; ONCOLOGY-GROUP; TIAZOFURIN 2-BETA-D-RIBOFURANOSYLTHIAZOLE-4-CARBOXAMIDE; PHARMACOKINETIC EVALUATION; INTRAVENOUS-INFUSION; ADVANCED CANCER AB Purpose: We evaluated the ratio of pediatric to adult maximum tolerated doses (MTDs) from 70 Phase I studies conducted between 1975 and 1995. The aim of this study was to determine whether previously observed differences in drug tolerance between adult and pediatric Phase I patients have persisted over the 20-year period of this analysis. Patients and Methods: Phase I trials of pediatric and adult patients with solid tumors as the predominant diagnosis and sharing similar dosing regimens were evaluated. For consistent comparison between Phase I studies, the MTD was defined as the drug dose one level below that yielding dose-limiting toxicity in >30% of patients. The ratio of pediatric to adult MTDs was calculated and plotted chronologically by year of pediatric study closure. Statistical evaluation of MTD ratios included regression and correlation analysis. The extent of therapy before Phase I study entry was also examined. Results: Ninety-three Phase I studies were reviewed. Twenty-one drugs (70 studies) met our criteria for paired review of MTDs and analysis of the variation of ratio with time. The pediatric to adult MTD ratios ranged from 0.4 to 2.8, with a median of 1.2. Regression analysis of the ratio of MTD versus date of pediatric study closure supports a linear relationship of decreasing ratio with time (p<0.01). Analysis of the regression line predicts MTD ratios of 2.02 and 0.76 for 1974 and 1995, respectively. Of patients included in this analysis, 37.1% and 68.6% of adult and pediatric patients, respectively, were considered to have been heavily pretreated before study entry. A significant (p<0.001) downward trend with time was observed in the proportion of adult patients entering Phase I studies who had received both radiation and chemotherapy. Conclusions: The results of this review continue to show an equal or greater drug tolerance in the pediatric population when compared with adult patients for most drugs studied during Phase I trials. However, there appears to be a significant trend of decreasing differences in drug tolerance between pediatric and adult Phase I patients with time, as defined by the descent of the MTD ratio toward values <1.0. Mechanisms to explain greater drug tolerance in children and the observation of decreasing maximum tolerated dose ratios with time are discussed. Limited data suggest that changes in degree of therapy before Phase I study entry may be influencing the MTD ratio. C1 UNIV TEXAS,SW MED CTR,DEPT PEDIAT HEMATOL & ONCOL,DALLAS,TX. UNIV TEXAS,SW MED CTR,DEPT ACAD COMP SERV,DALLAS,TX. NCI,CANC THERAPY EVALUAT PROGRAM,ROCKVILLE,MD. UNIV TEXAS,HLTH SCI CTR,DEPT PEDIAT HEMATOL & ONCOL,SAN ANTONIO,TX. INST DRUG DEV,SAN ANTONIO,TX. FU NCI NIH HHS [1-T32-CA09640] NR 83 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD AUG PY 1996 VL 18 IS 3 BP 250 EP 256 DI 10.1097/00043426-199608000-00003 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA VA002 UT WOS:A1996VA00200003 PM 8689336 ER PT J AU Mueller, BU Tannenbaum, S Pizzo, PA AF Mueller, BU Tannenbaum, S Pizzo, PA TI Bone marrow aspirates and biopsies in children with human immunodeficiency virus infection SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE bone marrows; human immunodeficiency virus; dysplasia; cytomegalovirus; Mycobacterium avium complex ID IMMUNE-DEFICIENCY SYNDROME; HEMATOLOGIC ABNORMALITIES; PROGENITOR CELLS; HIV-INFECTION; AIDS; FEATURES AB Purpose: Hematopoietic abnormalities are common in patients infected with the human immunodeficiency virus (HIV). We evaluated the role of diagnostic bone marrow aspirations and biopsies in HIV-infected children. Methods: Seventy-eight bone marrow biopsies and aspirates performed during the last 8 years at the Pediatric Branch of the National Cancer Institute from 60 children with symptomatic HIV infection were reviewed retrospectively. The results were correlated with clinical stage, use of antiretroviral therapy or hematopoietic growth factors, and hematopoietic parameters. Results: Most patients (84%) showed a normal or hypercellular marrow, associated with diffuse lymphocytosis (50%) or therapy with hematopoietic growth factors (33%). Dyspoietic features were very common in all three cell lineages. Twenty-seven (44%) of the patients had decreased iron stores in the bone marrow that correlated with iron deficiency as documented by serum tests in more than one-third of our study population. Bone marrow cultures were not more helpful than peripheral cultures in establishing the diagnosis of an opportunistic infection. Conclusion: Although bone marrow abnormalities are very common in HIV-infected children, they are rarely specific. The role of diagnostic bone marrow aspirates and biopsies appears to be limited, and this invasive procedure should be reserved for specific situations (e.g., to rule out a malignancy>. C1 NIH,SERV HEMATOL,DEPT CLIN PATHOL,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD. RP Mueller, BU (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,10 CTR DR MSC 1928,BETHESDA,MD 20892, USA. NR 26 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD AUG PY 1996 VL 18 IS 3 BP 266 EP 271 DI 10.1097/00043426-199608000-00006 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA VA002 UT WOS:A1996VA00200006 PM 8689339 ER PT J AU Bremer, JW Lew, JF Cooper, E Hillyer, GV Pitt, J Handelsman, E Brambilla, D Moye, J Hoff, R AF Bremer, JW Lew, JF Cooper, E Hillyer, GV Pitt, J Handelsman, E Brambilla, D Moye, J Hoff, R TI Diagnosis of infection with human immunodeficiency virus type 1 by a DNA polymerase chain reaction assay among infants enrolled in the Women and Infants' Transmission Study SO JOURNAL OF PEDIATRICS LA English DT Article ID CULTURE; HIV-1; LIFE AB Early diagnosis of infection with human immunodeficiency virus type 1 (HIV-1) in young infants is essential to decisions on their medical and social care, Whereas studies have suggested that polymerase chain reaction (PCR) is a sensitive and timely method of diagnosing HIV infection in children, these evaluations have been limited by the number of specimens studied, Recently, Roche Molecular Systems developed a complete HIV-1 DNA PCR testing kit (from specimen preparation to detection), In this study, use of this PCR test kit was evaluated for the detection of HIV infection in infants of seropositive mothers who were enrolled in the longitudinal, multicenter Women and Infants' Transmission Study. A total of 1209 blood specimens from 483 infants were tested and analyzed, The overall sensitivity and specificity of a single PCR test in determining HIV infection status in infants more than 1 but less than 36 months of age were 95% and 97%, respectively. For infected infants 1 to 6 months of age the sensitivity of the DNA-PCR test was 90% to 100%, In a direct comparison with coculture, the Roche DNA-PCR test was significantly more sensitive than coculture in the detection of HIV-1 in infected infants and was equivalent to coculture for the diagnosis of HIV in infants when a standardized algorithm was used to define infection status. C1 UNIV PUERTO RICO, MED CTR, SAN JUAN, PR 00936 USA. COLUMBIA UNIV COLL PHYS & SURG, DEPT PEDIAT, DIV INFECT DIS, NEW YORK, NY 10032 USA. SUNY HLTH SCI CTR, BROOKLYN, NY 11203 USA. NEW ENGLAND RES CTR, WATERTOWN, MA USA. NICHHD, PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH, NIH, BETHESDA, MD USA. NIAID, DIV AIDS, NIH, BETHESDA, MD 20892 USA. BOSTON CITY HOSP, BOSTON, MA 02118 USA. RP Bremer, JW (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR, DEPT MICROBIOL & IMMUNOL, 1653 W CONGRESS PKWY, CHICAGO, IL 60612 USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [N01-AI-85005, N01-AI-82507, N01-AI-82505] NR 22 TC 46 Z9 47 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1996 VL 129 IS 2 BP 198 EP 207 DI 10.1016/S0022-3476(96)70243-3 PG 10 WC Pediatrics SC Pediatrics GA VK797 UT WOS:A1996VK79700004 PM 8765616 ER PT J AU Daniels, SR Obarzanek, E Barton, BA Kimm, SYS Similo, SL Morrison, JA AF Daniels, SR Obarzanek, E Barton, BA Kimm, SYS Similo, SL Morrison, JA TI Sexual maturation and racial differences in blood pressure in girls: The National Heart, Lung, and Blood Institute Growth and Health Study SO JOURNAL OF PEDIATRICS LA English DT Article ID YOUNG-ADULTS; CHILDREN; MENARCHE; OBESITY; FATNESS; AGE AB Objective: To evaluate racial differences in blood pressure in girls aged 9 to 10 years in the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS) and to evaluate the extent to which racial differences in blood pressure are explained by other factors, including sexual maturation and body size. Methods: The NGHS enrolled 539 black and 616 white girls aged 9 years, and 674 black and 550 white girls aged 10 years. Racial differences in blood pressure were examined. Relationships of stage of sexual maturation, height, and skinfold thickness with systolic and diastolic blood pressure were evaluated by multiple regression analysis. Results: The black girls had significantly higher systolic (102.0 +/- 8.90 vs 100.5 +/- 9.42 mm Hg, p<0.001) and diastolic (58.0 +/- 12.0 vs 56.5 +/- 12.51 mm Hg, p<0.01) blood pressures than the white girls. The black girls were also more advanced in sexual maturation and were taller (142.9 +/- 7.94 vs 139.6 +/- 7.05, p<0.001) and heavier (39.6 +/- 11.24 vs 35.3 +/- 8.73 kg, p<0.001) than the white girls. Both systolic and diastolic blood pressure were significantly correlated with level of maturation, height, weight, and sum of skinfolds, Stage of maturation was found to account for the difference in blood pressure between black girls and white girls, In a multiple regression analysis, controlling for height (for diastolic blood pressure) and for both height and sum of skinfolds (for systolic blood pressure) eliminated the effects of race and stage of maturation on blood pressure. Conclusion: Racial differences in blood pressure were observed for 9- and 10-year-old girls and are explained by the fact that black girls were more mature than white girls. The effect of sexual maturation on blood pressure appears to operate through height and body fat. The effect of obesity may be more important for systolic than for diastolic blood pressure. Continuation of racial differences in blood pressure may result in a higher prevalence of hypertension for black women. C1 MARYLAND MED RES INST, BALTIMORE, MD 21010 USA. CHILDRENS HOSP, MED CTR, DIV CARDIOL, CINCINNATI, OH 45229 USA. UNIV PITTSBURGH, DEPT CLIN EPIDEMIOL & PREVENT MED, PITTSBURGH, PA USA. NHLBI, BETHESDA, MD 20892 USA. OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [HC55023-26] NR 21 TC 43 Z9 45 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1996 VL 129 IS 2 BP 208 EP 213 DI 10.1016/S0022-3476(96)70244-5 PG 6 WC Pediatrics SC Pediatrics GA VK797 UT WOS:A1996VK79700005 PM 8765617 ER PT J AU Heidbreder, CA Thompson, AC Shippenberg, TS AF Heidbreder, CA Thompson, AC Shippenberg, TS TI Role of extracellular dopamine in the initiation and long-term expression of behavioral sensitization to cocaine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID VENTRAL TEGMENTAL AREA; DISCRIMINATIVE STIMULUS PROPERTIES; RAT NUCLEUS-ACCUMBENS; FREELY MOVING RATS; AUTOMATED MEASUREMENT; INVIVO MICRODIALYSIS; D-AMPHETAMINE; TIME COURSE; QUANTITATIVE MICRODIALYSIS; PSYCHOMOTOR STIMULANT AB Repeated intermittent administration of cocaine has been shown to sensitize animals to the locomotor-activating effects of this agent. The neurobiochemical basis of this phenomenon, however, remains only partially understood. The present study sought to characterize basal dialysate dopamine (DA) concentrations within the nucleus accumbens (NAc), 2, 12 or 22 days after the cessation of either repeated cocaine (20 mg/kg/day x 5 days) or saline (1.0 ml/kg/day x 5 days) treatment. Locomotor activity and dialysate DA levels in response to a subsequent cocaine administration (20 mg/kg i.p.) were assessed at the same time intervals. Cocaine-pretreated animals exhibited an enhanced motor response to a cocaine injection 2 days after cessation of cocaine treatment. The magnitude of this effect increased progressively over time. Basal DA overflow was elevated 2 days after termination of cocaine treatment; at this time, however, a blunted response of DA neurons to the cocaine administration was observed. As the duration of withdrawal increased, basal dialysate DA concentrations gradually declined, whereas the response of DA neurons to cocaine progressively increased. By day 22 of withdrawal, a significant enhancement of cocaine-induced DA overflow was seen. These findings demonstrate that increased DA overflow in response to cocaine cannot account for the short-term expression of behavioral sensitization to cocaine. Rather, an enhanced DA response develops during later stages of the sensitization process and, therefore, may be one of the mechanisms responsible for the long-term expression of cocaine sensitization. RP Heidbreder, CA (reprint author), NIDA, BEHAV PHARMACOL & GENET SECT, PRECLIN PHARMACOL LAB, INTRAMURAL RES PROGRAM, POB 5180, BALTIMORE, MD 21224 USA. NR 71 TC 137 Z9 137 U1 2 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1996 VL 278 IS 2 BP 490 EP 502 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VA360 UT WOS:A1996VA36000006 PM 8768696 ER PT J AU Wagstaff, JD Gibb, JW Hanson, GR AF Wagstaff, JD Gibb, JW Hanson, GR TI Microdialysis assessment of methamphetamine-induced changes in extracellular neurotensin in the striatum and nucleus accumbens SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; DOPAMINERGIC REGULATION; SCHIZOPHRENIC-PATIENTS; ANTAGONIST SR-48692; MEDIATED CHANGES; MESSENGER-RNA; RECEPTORS; PATHWAYS; LOCALIZATION AB Stimulants of abuse such as cocaine and methamphetamine (METH) have dramatic effects on tissue neurotensin (NT) levels in the striatum and nucleus accumbens. Presumably these effects are due to the ability of such drugs to increase dopamine transmission. Because changes in dopamine activity appear to influence NT systems, we examined the effects of increasing doses of METH on extracellular NT levels in the medial striatum and nucleus accumbens using in vivo microdialysis in conscious rats. At the lowest dose tested (0.5 mg/kg), METH almost doubled the extracellular concentration of NT in both regions. When the dose of METH was increased to 5.0 mg/kg, extracellular NT concentration was elevated, but only to approximately 150% of control. At the highest dose examined (15.0 mg/kg), extracellular NT was not altered compared to pretreatment control levels. The role of DA D-1 and D-2 receptors in mediating these effects was determined by combining specific antagonists with the low dose of METH. The D-1 antagonist SCH 23390 blocked the METH-induced increase in extracellular NT levels in the striatum, but not in the nucleus accumbens. Pretreatment with the D-2 antagonist, eticlopride, blocked the increase in extracellular NT in both regions. Changes in striatal NT extracellular levels after a single METH injection were compared to the alterations in tissue NT levels following multiple administrations of the same doses of METH. Tissue levels were significantly elevated with 5 or 15 mg/kg METH in the medial, but not the lateral, striatum. There was not a clear correlation observed between the METH effects on striatal NT tissue levels and extracellular NT concentration. C1 UNIV UTAH,DEPT PHARMACOL & TOXICOL,SALT LAKE CITY,UT 84112. NIMH,NEUROPHYSIOL LAB,NIH,BETHESDA,MD 20892. FU NIDA NIH HHS [DA 00869, DA 5-09407] NR 51 TC 33 Z9 33 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1996 VL 278 IS 2 BP 547 EP 554 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VA360 UT WOS:A1996VA36000013 PM 8768703 ER PT J AU Villalobos, AR Dunnick, CA Pritchard, JB AF Villalobos, AR Dunnick, CA Pritchard, JB TI Mechanism mediating basolateral transport of 2,4-dichlorophenoxyacetic acid in rat kidney SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ORGANIC ANION TRANSPORT; STIMULATES PAH UPTAKE; MEMBRANE-VESICLES; RENAL TUBULES; PROXIMAL TUBULE; DICARBOXYLIC-ACIDS; P-AMINOHIPPURATE; WINTER FLOUNDER; CHOROID-PLEXUS; NET SECRETION AB The organic anions, p-aminohippurate (PAH) and fluorescein, are transported across the basolateral membrane of the renal proximal tubule in exchange for intracellular alpha-ketoglutarate (alpha KG), a mechanism indirectly coupled to sodium via Na+/alpha KG cotransport, To determine whether this mechanism mediates the basolateral transport of other organic anions, transport of the herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), was examined in rat renal cortical slices and basolateral membrane vesicles. In slices, uptake of 2,4-D increased steadily over time, approaching steady-state tissue/medium ratios of approximately 8 after 60 min. Probenecid, PAH and chlorophenol red inhibited steady-state uptake of 2,4-D. Accumulation of 10 mu M 2,4-D was stimulated 2-fold by 60 mu M glutarate; other dicarboxylic acids failed to stimulate uptake. In the presence of sodium, the addition of 5 mM LiCl or 2 mM ouabain to the bathing medium abolished glutarate stimulation. Removal of sodium from the bathing medium reversibly inhibited uptake as much as 75%. Furthermore, PAH inhibited 2,4-D uptake by slices in a dose-dependent manner, and increasing the external 2,4-D concentration decreased the inhibitory potency of PAH. In basolateral membrane vesicles, unlabeled 2,4-D inhibited sodium glutarate-coupled uptake of H-3-labeled PAH and 2,4-D in a concentration-dependent manner. Moreover, concentrative uptake of 2,4-D into vesicles could be driven by an outwardly directed gradient of glutarate or alpha KG that was generated by lithium-sensitive Na+/dicarboxylate cotransport or imposed experimentally. An outwardly directed gradient of unlabeled 2,4-D or PAH also stimulated uptake of 2,4-D. Based on these data, basolateral accumulation of 2,4-D by the renal proximal tubule is mediated by 2,4-D/alpha KG exchange, a mechanism energetically coupled to Na+/alpha KG cotransport and shared with PAH. RP Villalobos, AR (reprint author), NIEHS,CELLULAR & MOL PHARMACOL LAB,COMPARAT MEMBRANE PHARMACOL SECT,NIH,MD 7-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 22 Z9 22 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1996 VL 278 IS 2 BP 582 EP 589 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VA360 UT WOS:A1996VA36000017 PM 8768707 ER PT J AU Lockwood, LL Silvert, LH Fleshner, MR McNeal, C Watkins, LR Laudenslager, ML Rice, KC Weber, RJ Maier, SF AF Lockwood, LL Silvert, LH Fleshner, MR McNeal, C Watkins, LR Laudenslager, ML Rice, KC Weber, RJ Maier, SF TI Morphine-induced alterations in antibody levels: Receptor and immune mechanisms SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NATURAL-KILLER ACTIVITY; OPIOID RECEPTORS; INDUCED MODULATION; CONSCIOUS RATS; SUPPRESSION; LYMPHOCYTES; RESPONSES; INVIVO; CELLS; IMMUNOSUPPRESSION AB We have previously shown that an acute administration of morphine (10 mg/kg, i.v.) decreases IgG, but not IgM, antibody levels to antigen administered before morphine. Further, decreases in IgG were blocked by previous administration of naltrexone, indicating that receptor binding is critical to the decreased antibody levels. These studies investigated potential receptor and immune mechanisms for these effects. To investigate potential receptor mechanisms, the stereoselectivity and location of receptor binding was determined. The results of these experiments suggest morphine must bind stereoselectively to central sites to decrease antibody levels after antigen administration. To investigate potential immune mechanisms for these changes, antibody secreting cells (ASC) for keyhole limpet hemocyanin-specific IgG and IgM were enumerated. Morphine decreased ASC for IgG but increased ASC for IgM. Two pathways for the genetic switch from IgM to IgG production were investigated. One pathway requires interferon-gamma to stimulate IgM-secreting cells to switch to IgG2a-secreting cells. Another pathway requires interleukin-4, to stimulate IgM-secreting cells to switch to IgG1- secreting cells. IgG1 and IgG2a levels were measured to determine if these pathways were differentially affected and only IgG2a levels were decreased. Further, these decreases were accompanied by decreased IFN-gamma levels but not by altered numbers of splenocytes. These data indicate that morphine may alter the ability of ASC to switch from IgM to IgG2a production, possibly by reducing the availability of IFN-gamma. C1 UNIV COLORADO,DEPT PSYCHOL,BOULDER,CO 80309. UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. NIMH,NIDDK,BETHESDA,MD 20892. UNIV ILLINOIS,COLL MED,DEPT BASIC SCI,PEORIA,IL 61656. RP Lockwood, LL (reprint author), METROPOLITAN STATE COLL,DEPT PSYCHOL,POB 173362,CAMPUS BOX 54,DENVER,CO 80217, USA. OI Laudenslager, Mark/0000-0002-9815-3026 FU NIMH NIH HHS [MH37373, MH45045] NR 54 TC 9 Z9 10 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1996 VL 278 IS 2 BP 689 EP 696 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VA360 UT WOS:A1996VA36000030 PM 8768720 ER PT J AU Matsuoka, N Aigner, TG AF Matsuoka, N Aigner, TG TI D-cycloserine, a partial agonist at the glycine site coupled to N-methyl-D-aspartate receptors, improves visual recognition memory in rhesus monkeys SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; XENOPUS OOCYTES; MODULATORY SITE; LEARNING-TASKS; EVOKED RELEASE; BINDING-SITES; AMINO-ACIDS; RAT-BRAIN; NMDA AB Strychnine-insensitive glycine binding sites have recently been shown to positively modulate N-methyl-D-aspartate (NMDA) receptors. In the present study, the effects on recognition memory of D-cycloserine, a partial agonist at the glycine modulatory site on the NMDA receptor, were evaluated in rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample (DNMS) with a list length of 20 trial-unique graphic symbols. Single administration of D-cycloserine (100-1000 mu g/kg i.m.) facilitated DNMS performance significantly with an inverted U-shaped dose-response curve when given 30 min before testing. To assess further the possible neural mechanisms, D-cycloserine was evaluated for its effects on the memory impairments after blockade of the glycine sites by HA-966, N-methyl-D-aspartate receptors by MK-801, or cholinergic receptors by scopolamine. D-Cycloserine completely reversed the visual recognition memory deficits produced by HA-966 (3.2 mg/kg i.m.). D-Cycloserine also dose-dependently and significantly restored the memory deficits produced by MK-801 (32 mu g/kg i.m.). In addition, D-cycloserine produced a partial, though significant: improvement on the recognition memory deficits after cholinergic blockade with scopolamine (10 mu g/kg i.m.). From these results, we propose that D-cycloserine has a cognition-enhancing property in nonhuman primates and that it may have a potential value in treating dementias. Furthermore, the present results provide new evidence for the important role for the glycine sites in the regulation of recognition memory. C1 NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. NR 52 TC 58 Z9 58 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1996 VL 278 IS 2 BP 891 EP 897 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VA360 UT WOS:A1996VA36000054 PM 8768744 ER PT J AU Tycko, R Reimer, JA AF Tycko, R Reimer, JA TI Optical pumping in solid state nuclear magnetic resonance SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID LASER-POLARIZED XE-129; GAAS QUANTUM-WELLS; HIGH-PURITY GAAS; SPIN-EXCHANGE; CROSS-POLARIZATION; GALLIUM-ARSENIDE; ELECTRONIC-PROPERTIES; ALKALI FULLERIDES; POLYMER SURFACE; PUMPED XENON AB An important current trend in solid state nuclear magnetic resonance (NMR) is the growing exploitation of optical pumping of nuclear spin polarizations as a means of enhancing and localizing NMR signals. Recent work has been concentrated in two areas, namely optically pumped NMR in semiconductors and optical pumping of noble gases. Progress in these two areas, including technical developments and new applications in physical chemistry, condensed matter physics, and biomedical sciences, is reviewed. Likely directions for future developments are suggested. C1 UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,CTR ADV MAT,BERKELEY,CA 94720. UNIV CALIF BERKELEY,DEPT CHEM ENGN,BERKELEY,CA 94720. RP Tycko, R (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892, USA. NR 74 TC 57 Z9 57 U1 4 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD AUG 1 PY 1996 VL 100 IS 31 BP 13240 EP 13250 DI 10.1021/jp953667u PG 11 WC Chemistry, Physical SC Chemistry GA VA595 UT WOS:A1996VA59500039 ER PT J AU Knox, RJ Jonas, EA Kao, LS Smith, PJS Connor, JA Kaczmarek, LK AF Knox, RJ Jonas, EA Kao, LS Smith, PJS Connor, JA Kaczmarek, LK TI Ca2+ influx and activation of a cation current are coupled to intracellular Ca2+ release in peptidergic neurons of Aplysia californica SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID RAT MAST-CELLS; CALCIUM CHANNELS; SYMPATHETIC NEURONS; ION CHANNELS; GROWTH CONES; STORES; SINGLE; ENTRY; SITES AB 1. Stimulation of inputs to bag cell neurons in the abdominal ganglion of Aplysia californica causes an increase in their intracellular Ca2+ concentration ([Ca2+](i)). We have used thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca2+ pump, to analyse the effects of Ca2+ released from intracellular stores on the electrophysiological responses of bag cell neurons. 2. Using digital imaging of fura-2-loaded isolated bag cell neurons we found that thapsigargin rapidly evoked an increase in [Ca2+](i) in somata, with smaller increases in neurites. Thapsigargin-induced elevation of [Ca2+](i) peaked at about 1 mu M within 5-10 min and then decayed to basal levels by 30 min. 3. Placement of an extracellular vibrating Ca2+-selective microelectrode to within 1 mu m of somata revealed a relatively large steady-state Ca2+ efflux. Thapsigargin produced a rapid increase in Ca2+ influx. Changes in Ca2+ flux were not detected at neurites. 4. Thapsigargin produced a small depolarization in isolated bag cell neurons in artificial sea water (ASW). Sometimes enhanced depolarizations were observed when extracellular Naf was replaced by TEA or Tris, but not N-methyl-D-glucamine (NMDG). The depolarization was not blocked by 100 mu M tetrodotoxin (TTX), removal of extracellular Ca2+ (0.5 mM EGTA) or addition of 10 mM Co2+ to the bath solution. 5. In voltage-clamp experiments, thapsigargin induced an inward current (I-Tg) that was recorded in Ca2+-free media containing TEE or Tris substituted for Na+. The apparent reversal potential of I-Tg was -16.8 +/- 1.2 mV in TEA-ASW. Induction of I-Tg was inhibited in neurons that were microinjected with the Ca2+ chelator BAPTA-Dextran(70) or treated with the membrane-permeant analogue BAPTA AM. Activation of I-TG was not observed when Na+ was replaced with NMDG. Manipulation of [Na+](0) and [K+](0) produced shifts in the reversal potential of I-Tg consistent with the underlying channels being permeable to both Na+ and K+. 6. Thapsigargin did not alter the amplitude or kinetics of voltage-activated Ba2+ currents, but in some experiments it did increase the amplitude of a component of out-ward K+ current. 7. Thapsigargin neither induced bag cell neurons within the intact ganglion to depolarize and fire spontaneously, nor did it alter the frequency or duration of firing of an electrically stimulated bag cell after-discharge. 8. We conclude that thapsigargin-sensitive Ca2+ pools are present predominantly in the somata of bag cell neurons. Ca2+ that is released from thapsigargin-sensitive Ca2+ stores activates a non-selective cation current that may help sustain depolarization of the somata, but does not by itself trigger an after-discharge. C1 ACAD SINICA,INST BIOMED SCI,TAIPEI 11529,TAIWAN. MARINE BIOL LAB,NATL VIBRATING PROBE FACIL,NIH,WOODS HOLE,MA 02543. LOVELACE BIOMED & ENVIRONM RES INST,CELL BIOL LAB,ALBUQUERQUE,NM 87108. RP Knox, RJ (reprint author), YALE UNIV,DEPT PHARMACOL,NEW HAVEN,CT 06520, USA. FU NINDS NIH HHS [NS-18492] NR 38 TC 30 Z9 31 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD AUG 1 PY 1996 VL 494 IS 3 BP 627 EP 639 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VE395 UT WOS:A1996VE39500002 PM 8865062 ER PT J AU Listwak, SJ Gold, PW Whitfield, HJ AF Listwak, SJ Gold, PW Whitfield, HJ TI The human mineralocorticoid receptor gene promoter: Its structure and expression SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENOCORTICAL SYSTEM; HUMAN GLUCOCORTICOID RECEPTOR; DNA-SEQUENCE REQUIREMENTS; MESSENGER-RNA; TYROSINE-HYDROXYLASE; CELL-LINE; THERAPEUTIC IMPLICATIONS; COMPLEMENTARY-DNA; MOLECULAR-CLONING AB The structure and expression of a clone containing the promoter region, all of exon 1, and part of the first intron of the human mineralocorticoid receptor (hMR) gene is presented. The clone has three sets of CAAT and TATA elements, one located at the very 5'-end of the clone, one located just 5'- to the start of transcription, and one set located in intron A, approximately 300 bp into the intron. The major start of transcription site by primer extension analysis and ribonuclease protection assays is located 26 bp downstream of a TATA-like box (TTTAA) and 90 and 143 bp downstream, respectively, of two CCAAT boxes. Putative cis-transcription factor binding sites are as follows: two potential AP1 sites, one potential AP2 site, two ATF/CREB sites, six potential GC boxes or SP1 sites, one potential perfect half-palindromic estrogen response element, and three potential PEA3 sites. Therefore, the hMR promoter region contains elements characteristic of both regulated genes and ''housekeeping'' genes. CAT assays of overlapping deletions of the promoter region demonstrated tissue-specific regulation in human neuroepithelioma (SK-N-MC-IXC) and non-neuronal, peripheral choriocarcinoma cell lines (JEG-3). Copyright (C) 1996 Elsevier Science Ltd. C1 UNIV ILLINOIS,DEPT PSYCHIAT MC 912,COLL MED,CHICAGO,IL 60612. UNIV ILLINOIS,DEPT BIOL CHEM,COLL MED,CHICAGO,IL 60612. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 49 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD AUG PY 1996 VL 58 IS 5-6 BP 495 EP 506 DI 10.1016/0960-0760(96)00072-6 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA VU248 UT WOS:A1996VU24800005 PM 8918975 ER PT J AU Hoagwood, K Jensen, PS Petti, T Burns, BJ AF Hoagwood, K Jensen, PS Petti, T Burns, BJ TI Outcomes of mental health care for children and adolescents .1. A comprehensive conceptual model SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE children and adolescents; outcomes; clinical efficacy; service effectiveness; managed care; health care ID DIAGNOSTIC INTERVIEW SCHEDULE; PSYCHIATRIC-ASSESSMENT CAPA; TEST-RETEST RELIABILITY; SERVICE USE; PSYCHOTHERAPY; EPIDEMIOLOGY; COMPETENCE; CULTURE AB Objective: Accountability for mental health care has become a standard of clinical practice. With the expansion of managed care as a corporate response to health reform, attention to outcomes will intensify. Assessment of clinical treatment has typically focused on symptom reduction at an individual level, whereas assessment of service effectiveness has more often targeted service-level change. Method: A dynamic and interactional model of outcomes is presented that broadens the range of intended consequences of care. The model comprises five domains: symptoms, functioning, consumer perspectives, environmental contexts, and systems. Results: The model reflects the changeable interaction between children's evolving capacities and their primary environments (home, school, and community). Conclusions: As health care practices shift, attention to improved care is likely to depend increasingly on scientifically credible evidence of its impact. Greater integration between research and standard practice will be needed. Such a partnership can be strengthened by a more comprehensive view of the impact of care. C1 INDIANA UNIV,DEPT PSYCHIAT,INDIANAPOLIS,IN 46202. NIMH,ROCKVILLE,MD 20857. DUKE UNIV,DEPT PSYCHIAT,DURHAM,NC 27706. OI Jensen, Peter/0000-0003-2387-0650 NR 65 TC 131 Z9 132 U1 7 U2 12 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 1996 VL 35 IS 8 BP 1055 EP 1063 DI 10.1097/00004583-199608000-00017 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UY926 UT WOS:A1996UY92600017 PM 8755803 ER PT J AU Jensen, PS Hoagwood, K Petti, T AF Jensen, PS Hoagwood, K Petti, T TI Outcomes of mental health care for children and adolescents .2. Literature review and application of a comprehensive model SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE outcomes efficacy; efficacy; effectiveness; mental health services; treatment; children and adolescents ID SERIOUS JUVENILE-OFFENDERS; FOLLOW-UP; AUTISTIC-CHILDREN; BEHAVIORAL TREATMENT; DEPRESSIVE DISORDER; ANTISOCIAL-BEHAVIOR; CASE-MANAGEMENT; FOSTER-CARE; THERAPY; TERM AB Objective: Using a comprehensive model of outcomes, the authors reviews the scientific literature to determine the extent of knowledge concerning the outcomes of mental health care for children and adolescents. Method: Previous research is examined to determine the degree to which it addresses live salient outcome domains: symptoms/diagnoses, functioning, consumer perspectives, environments, and systems (the SFCES model). Results: Despite numerous studies, only 38 met minimal scientific criteria. They generally fall into two categories, according either to their focus on the efficacy of treatment(s) for specific disorders or the effectiveness of a particular service or service system. Only two studies include outcome assessments across all five domains. Conclusions: As health care practices shift, improvements in mental health care will require credible evidence detailing the impact of clinical treatments and services oa ail salient outcome domains. Embedding efficacious treatments into effective service programs will likely improve care, but treatments will require modification to make them flexible, inclusive, and appropriate to multicultural populations. Furthermore, service delivery systems must be modified to meet the specific clinical needs of children with mental disorders and to embrace new efficacious treatments as they become available. C1 NIMH,ROCKVILLE,MD 20857. INDIANA UNIV,DEPT PSYCHIAT,DIV CHIL & ADOLESCENT PSYCHIAT,INDIANAPOLIS,IN 46204. OI Jensen, Peter/0000-0003-2387-0650 NR 84 TC 75 Z9 77 U1 4 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 1996 VL 35 IS 8 BP 1064 EP 1077 DI 10.1097/00004583-199608000-00018 PG 14 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UY926 UT WOS:A1996UY92600018 PM 8755804 ER PT J AU Dilsizian, V AF Dilsizian, V TI Myocardial viability: Contractile reserve or cell membrane integrity? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID LEFT-VENTRICULAR DYSFUNCTION; CORONARY-ARTERY DISEASE; POSITRON EMISSION TOMOGRAPHY; VIABLE MYOCARDIUM; F-18 FLUORODEOXYGLUCOSE; THROMBOLYTIC THERAPY; DOBUTAMINE; INFARCTION; ECHOCARDIOGRAPHY; REINJECTION RP Dilsizian, V (reprint author), NIH,10 CTR DR MSC 118,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 24 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG PY 1996 VL 28 IS 2 BP 443 EP 446 DI 10.1016/0735-1097(96)83110-X PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UZ529 UT WOS:A1996UZ52900025 PM 8800123 ER PT J AU Slavkin, HC AF Slavkin, HC TI Biomimetics: Replacing body parts is no longer science fiction SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD AUG PY 1996 VL 127 IS 8 BP 1254 EP 1257 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VB734 UT WOS:A1996VB73400029 PM 8803404 ER PT J AU Smith, CJ Nelson, RG Hardy, SA Manahan, EM Bennett, PH Knowler, WC AF Smith, CJ Nelson, RG Hardy, SA Manahan, EM Bennett, PH Knowler, WC TI Survey of the diet of Pima Indians using quantitative food frequency assessment and 24-hour recall SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID NUTRIENT DATA-BASE; STANDARD REFERENCE; REPRODUCIBILITY; HISTORY; WOMEN AB Objective A dietary survey was conducted in the Gila River Indian Community in Arizona using two methods of dietary assessment - 24-hour recall and quantitative food frequency (QFF) assessment - to determine the usual intake of the population. Design Interviews were conducted by Pima women who were trained and monitored by a research dietitian. Energy and nutrient intake were calculated using a computerized dietary database that included specific Pima foods. Subjects An age- and sex-stratified sample of 575 Pima Indians (273 men, 302 women) aged 18 to 74 years participated in the study. Statistical analyses Spearman correlations were used to compare the results of the two survey methods fur energy and each nutrient. Intraclass correlations were used to measure reproducibility. Results According to the 24-hour recall, mean reported energy intakes within decades of age were 95% to 112% of those in the US population for Pima women, and 76% to 94% of those in the US population for Pima men. Total energy intake assessed using QFF was 30% higher in men and 33% higher in women than the intake assessed using the 24-hour recall method. Conclusions A large dietary survey conducted using lay interviewers in a Native-American community was as reproducible as studies conducted in the general US population. The Pima diet was distributed among the major nutrients in a proportion similar to the US diet. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ 85014. CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,PHOENIX,AZ. RI Nelson, Robert/B-1470-2012 FU NIDDK NIH HHS [N01-DK-6-2285] NR 36 TC 51 Z9 52 U1 0 U2 2 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD AUG PY 1996 VL 96 IS 8 BP 778 EP 784 DI 10.1016/S0002-8223(96)00216-7 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VF445 UT WOS:A1996VF44500025 PM 8683009 ER PT J AU Hodes, RJ McCormick, AM Pruzan, M AF Hodes, RJ McCormick, AM Pruzan, M TI Longevity assurance genes: How do they influence aging and life span? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ELEGANS DAUER LARVA; CAENORHABDITIS-ELEGANS; DROSOPHILA-MELANOGASTER; SUPEROXIDE-DISMUTASE; OXIDATIVE DAMAGE; SELECTION; OVEREXPRESSION; SENESCENCE; APOPTOSIS; MUTATION RP Hodes, RJ (reprint author), NIA,BLDG 31,RN 5C35,CTR DR,MSC2292,BETHESDA,MD 20892, USA. NR 32 TC 5 Z9 5 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1996 VL 44 IS 8 BP 988 EP 991 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VA563 UT WOS:A1996VA56300019 PM 8708315 ER PT J AU Baum, BJ AF Baum, BJ TI Oral health for the older patient SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material RP Baum, BJ (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1996 VL 44 IS 8 BP 997 EP 998 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VA563 UT WOS:A1996VA56300022 PM 8708318 ER PT J AU Moul, DE AF Moul, DE TI Mental health services research on the aging: New opportunities and challenges for clinical researchers SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID QUALITY RP Moul, DE (reprint author), NIMH,SERV RES BRANCH,AGING MENTAL HLTH SERV SECT,ROOM 10C-06,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1996 VL 44 IS 8 BP 999 EP 1000 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VA563 UT WOS:A1996VA56300023 PM 8708319 ER PT J AU Agostino, R Sanes, JN Hallet, M AF Agostino, R Sanes, JN Hallet, M TI Motor skill learning in Parkinson's disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Parkinson's disease; basal ganglia; motor skill learning; motor adaptation ID EVOKED-POTENTIALS; IMPLICIT MEMORY; ARM MOVEMENTS; ABNORMALITIES; DYSFUNCTION; INFORMATION; PERFORMANCE; ADAPTATION; TRACKING; LESIONS AB The motor performance of patients with Parkinson's disease is degraded, but it is unclear whether their motor learning (adaptation learning and skill learning) ability is impaired. To assess the ability of these patients to learn motor tasks, we studied nine Parkinson's disease patients and eight age-matched normal (control) subjects who repetitively traced, as rapidly and accurately as possible, irregular geometric patterns with normal and mirror-reversed vision. The outcome was measured by statistical analysis and graphic plotting of values for actual and standardized performance variables and correlation of data from initial and final performance variables with indicators of disease severity. The results showed that, with normal vision, total movement time was reduced in both patients and normal subjects, but movement errors increased with repetition, apparently reflecting a speed-accuracy trade-off and adaptation learning. With mirror-reversed vision, total movement time and movement errors were reduced equally with repetition in both groups. These concomitant improvements in time and accuracy violate the rule of speed-accuracy trade-off and suggest that this behavior reflects true motor skill learning. We conclude that patients with Parkinson's disease do not differ from normal subjects in the processes of motor adaptation and motor skill learning. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. BROWN UNIV,DEPT NEUROSCI,DIV BIOL & MED,PROVIDENCE,RI 02912. NR 45 TC 49 Z9 51 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD AUG PY 1996 VL 139 IS 2 BP 218 EP 226 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VC065 UT WOS:A1996VC06500009 PM 8856656 ER PT J AU Walther, MM Linehan, WM AF Walther, MM Linehan, WM TI Nephron sparing surgery for renal cell carcinoma in von Hippel-Lindau disease SO JOURNAL OF UROLOGY LA English DT Letter RP Walther, MM (reprint author), NCI,NIH,DCT,COP,SB,UROL ONCOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2B-43,10 CTR DR,BETHESDA,MD 20898, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1996 VL 156 IS 2 BP 480 EP 481 PN 1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA UX152 UT WOS:A1996UX15200046 PM 8683709 ER PT J AU Rein, A Ott, DE Mirro, J Arthur, LO Rice, W Henderson, LE AF Rein, A Ott, DE Mirro, J Arthur, LO Rice, W Henderson, LE TI Inactivation of murine leukemia virus by compounds that react with the zinc finger in the viral nucleocapsid protein SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-ANEMIA VIRUS; CYS-HIS BOX; REVERSE TRANSCRIPTION; STRAND TRANSFER; TYPE-1; RNA; SEQUENCES; DNA; MUTATIONS AB All retroviral nucleocapsid (NC) proteins, except those of spumaretroviruses, contain one or two copies of the conserved sequence motif C-X(2)-C-X(4)-H-X(4)-C. The conserved cysteine and histidine residues coordinate a zinc ion in each such motif, Rice et al. (W. G. Rice, J. G. Supko, L. Malspeis, R. W. Buckheit, Jr., D. Clanton, M. Bu, L. Graham, C. A. Schaeffer, J. A. Turpin, J. Domagala, R. Gogliotti, J. P. Bader, S. M. Halliday, L. Coren, R. C. Sowder II, L. O. Arthur, and L. E. Henderson, Science 270:1194-1197, 1995) have described a series of compounds which inactivate human immunodeficiency virus type 1 (HIV-1) particles and oxidize the cysteine thiolates in the NC zinc finger, We have characterized the effects of three such compounds on Moloney murine leukemia virus (MuLV), We find that, as with HIV-1, the compounds inactivate cell-free MuLV particles and induce disulfide cross-linking of NC in these particles, The killed MuLV particles were found to be incapable of synthesizing full-length viral DNA upon infection of a new host cell, When MuLV particles are synthesized in the presence of one of these compounds, the normal maturational cleavage of the Gag polyprotein does not occur, The compounds have no effect on the infectivity of human foamy virus, a spumaretrovirus lacking zinc fingers in its NC protein, The resistance of foamy virus supports the hypothesis that the zinc fingers are the targets for inactivation of MuLV and HIV-1 by the compounds, The absolute conservation of the zinc finger motif among oncoretroviruses and lentiviruses and the lethality of all known mutations altering the zinc-binding residues suggest that only the normal, wild-type structure can efficiently perform all of its functions, This possibility would make the zinc finger an ideal target for antiretroviral agents. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,LAB ANTIVIRAL DRUG MECH,FREDERICK,MD 21702. RP Rein, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC,ABL BASIC RES PROGRAM,RETROVIRAL GENET SECT,POB B,FREDERICK,MD 21702, USA. NR 38 TC 31 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1996 VL 70 IS 8 BP 4966 EP 4972 PG 7 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200013 PM 8764002 ER PT J AU Samal, SK Collins, PL AF Samal, SK Collins, PL TI RNA replication by a respiratory syncytial virus RNA analog does not obey the rule of six and retains a nonviral trinucleotide extension at the leader end SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; GENOMIC RNA; SEQUENCE HETEROGENEITY; SYNTHETIC ANALOGS; SENDAI VIRUS; CLONED CDNA; RESCUE; TRANSCRIPTS; EXPRESSION; TERMINI AB Genome analogs (''minigenomes'') of Sendai and measles viruses replicate efficiently only if their nucleotide length is an even multiple of six, a requirement called the rule of six (P. Calain and L. Roux, J. Virol. 67:4822-4830, 1993; M. S. Sidhu, J. Chan, K. Kaelin, P. Spielhofer, F. Radecke, H. Schneider, M. Masurekar, P. C. Dowling, M. A. Billeter, and S. A. Udem, Virology 208:800-807, 1995). The existence of a comparable requirement was tested for respiratory syncytial virus (RSV), which also is a member of family Paramyxoviridae and whose natural genome length also is a multiple of six. An internally truncated analog of RSV positive-sense replicative intermediate RNA (antigenome) bearing the chloramphenicol acetyltransferase gene as a reporter was synthesized from cDNA in vitro. This RNA was transfected into cells which were infected with RSV as a helper. Miniantigenomic RNA was indistinguishable from previously studied negative-sense minigenome RNA in its ability to participate in transcription, RNA replication, and incorporation into transmissible particles. Sixteen miniantigenomes which were of slightly different lengths and which in aggregate represented multiples of a wide range of integers including 1 to 15 were constructed. During transfection and two serial passages, the various miniantigenomes were essentially indistinguishable with regard to the efficiency of transcription, RNA replication, and packaging into transmissible particles. Progeny minigenomes of six different mutants were recovered postpassage, copied into cDNA, cloned, and sequenced completely. The length of each of these RNAs was found to have remained unchanged during replication and passage. Thus, RSV transcription and replication appear to lack the requirement that the template length be an even multiple of an integer such as six, which for Sendai and measles viruses is obligatory for nucleocapsid function. Each of the in vitro-synthesized miniantigenomes used in transfection contained a nonviral extension of three nucleotides, GGG,,on the 5' (leader) end contributed by the T7 promoter. The termini of the recovered minigenomes were examined for five mutants by RNA circularization followed by cDNA synthesis, amplification, cloning, and sequencing. Unexpectedly, each recovered minigenome contained the complement of this nonviral extension on the 3' (leader) end, showing that it had been faithfully copied and maintained during RNA replication and passage. The nonviral trinucleotide did not appear to affect the activity of the template. C1 NIAID,NIH,INFECT DIS LAB,BETHESDA,MD 20892. UNIV MARYLAND,REG COLL VET MED,COLLEGE PK,MD 20742. NR 40 TC 65 Z9 68 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1996 VL 70 IS 8 BP 5075 EP 5082 PG 8 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200026 PM 8764015 ER PT J AU Powell, MD Levin, JG AF Powell, MD Levin, JG TI Sequence and structural determinants required for priming of plus-strand DNA synthesis by the human immunodeficiency virus type 1 polypurine tract SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; RNASE-H ACTIVITIES; HIV-1 REVERSE-TRANSCRIPTASE; ROUS-SARCOMA VIRUS; NUCLEOTIDE-SEQUENCE; AIDS VIRUS; AVIAN-MYELOBLASTOSIS; ANGSTROM RESOLUTION; FEATURES IMPORTANT; CRYSTAL-STRUCTURE AB At the 3' end of all retroviral genomes there is a short, highly conserved sequence known as the polypurine tract (PPT), which serves as the primer for plus-strand DNA synthesis. We have identified the determinants for in vitro priming by the human immunodeficiency virus type 1 (HIV-1) PPT. We show that when the PPT is removed and placed into different nucleotide contexts, new priming sites are produced at the precise 3' end of the PPT. In addition, we find that a hybrid consisting of a 15- or 20-nucleotide RNA primer annealed to a 35-nucleotide DNA template is competent for initiation of plus-strand synthesis with HIV-1 reverse transcriptase. Thus, no cis-acting elements appear to be required for priming activity. Changes at the 5' end of the PPT have no effect on primer function, whereas the identity of bases at the 3' end is crucial. A primer containing only the 6 G residues from the 3' end of the wild-type PPT sequence and 9 bases of random sequence at the 5' end functions like a wild-type PPT. A short hybrid having a similar helical structure but a primary sequence different from that of the PPT is cleaved imprecisely, resulting in initiation of synthesis at multiple sites; however, total primer extension is close to the wild-type level. We conclude that helical structure as well as the presence of particular bases at the 3' end of the PPT is essential for PPT function. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 64 TC 79 Z9 79 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1996 VL 70 IS 8 BP 5288 EP 5296 PG 9 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200050 PM 8764039 ER PT J AU Alkhatib, G Broder, CC Berger, EA AF Alkhatib, G Broder, CC Berger, EA TI Cell type-specific fusion cofactors determine human immunodeficiency virus type 1 tropism for T-cell lines versus primary macrophages SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; BACTERIOPHAGE-T7 RNA-POLYMERASE; CD26 ANTIGEN; HIV FUSION; MEMBRANE-FUSION; PRODUCTIVE INFECTION; CD4-MEDIATED FUSION; VIRAL DETERMINANTS; EXPRESSION SYSTEM; FOREIGN GENES AB Work in this laboratory previously demonstrated that the tropism of different human immunodeficiency type 1 isolates for infection of human CD4(+) continuous cell lines (e.g., T-cell lines and HeLa-CD4 transformants) versus primary macrophages is associated with parallel intrinsic fusogenic specificities of the corresponding envelope glycoproteins (Envs). For T-cell line-tropic isolates, it is well established that the target cell must also contain a human-specific fusion cofactor(s) whose identity is unknown. In this study, we tested the hypothesis that the Fm fusion specificities underlying T-cell line versus macrophage tropism are determined by distinct cell type-specific fusion cofactors. We applied a recombinant vaccinia virus-based reporter gene assay for Env-CD4-mediated cell fusion; the LAV and Ba-L Envs served as prototypes for T-cell line-tropic and macrophage-tropic isolates, respectively. We examined CD4(+) promyeloctic and monocytic cell lines that are infectible by T-cell line-tropic isolates and become susceptible to macrophage-tropic strains only after treatment with differentiating agents. We observed parallel changes in fusion specificity: untreated cells supported fusion by the LAV but not the Ba-L Env, whereas cells treated with differentiating agents acquired fusion competence for Ba-L. These results suggest that in untreated cells, the block to infection by macrophage-tropic isolates is at the level of membrane fusion; furthermore, the differential regulation of fusion permissiveness for the two classes of Envs is consistent with the existence of distinct fusion cofactors. To test this notion directly, we conducted experiments with transient cell hybrids formed between CD4-expressing nonhuman cells (murine NIH 3T3) and different human cell types. Hybrids formed with HeLa cells supported fusion by the LAV Env but not by the Ba-L Env, whereas hybrids formed with primary macrophages showed the opposite specificity; hybrids formed between HeLa cells and macrophages supported fusion by both Envs. These results suggest the existence of cell type-specific fusion cofactors selective for each type of Env, rather than fusion inhibitors for discordant Env-cell combinations. Finally, analyses based on recombinant protein expression and antibody blocking did not support the proposals by others that the CD44 or CD26 antigens are involved directly in the entry of macrophage-tropic isolates. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NR 57 TC 96 Z9 97 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1996 VL 70 IS 8 BP 5487 EP 5494 PG 8 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200071 PM 8764060 ER PT J AU Kashanchi, F Khleif, SN Duvall, JF Sadaie, MR Radonovich, MF Cho, M Martin, MA Chen, SY Weinmann, R Brady, JN AF Kashanchi, F Khleif, SN Duvall, JF Sadaie, MR Radonovich, MF Cho, M Martin, MA Chen, SY Weinmann, R Brady, JN TI Interaction of human immunodeficiency virus type 1 Tat with a unique site of TFIID inhibits negative cofactor Dr1 and stabilizes the TFIID-TFIIA complex SO JOURNAL OF VIROLOGY LA English DT Article ID RNA-POLYMERASE-II; BOX-BINDING-PROTEIN; TRANSCRIPTION FACTOR; ACTIVATES TRANSCRIPTION; ELONGATION COMPLEXES; GENE-TRANSCRIPTION; KAPOSIS-SARCOMA; IN-VITRO; INITIATION; INVITRO AB We have previously reported the direct physical interaction between the human immunodeficiency virus (HIV) type 1 Tat protein and the basal transcription factor TBP/TFIID. Affinity chromatography demonstrated that wild-type Tat, but not a transactivation mutant of Tat, was capable of depleting TBP/TFIID from cell extracts. These experiments represented the first demonstration of a basal transcription factor that binds, in an activation-dependent manner, to Tat. We now report that the Tat-TBP interaction can be detected in HIV type 1-infected cells. The domain of TBP interacting with Tat has been mapped from amino acids 163 to 196 by using deletion and site-specific mutants of TBP. This domain of TBP, which includes the H1 and S2 domains, is distinct from the H2 binding site for other activator proteins, such as E1A. The interaction of Tat with TFIID regulates the binding of accessory proteins to TFIID. Tat stabilizes the interaction of TFIID with TFIIA in a gel shift assay. In addition, Tat competes for Drl interaction with TBP. bur results suggest that the basal transcription factor TBP/TFIID represents an important regulatory molecule in HIV transcription. C1 NCI,MOLEC VIROL LAB,NIH,BETHESDA,MD 20892. NCI,NAVY MED ONCOL BRANCH,NIH,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,ROCKVILLE,MD 20859. BRISTOL MYERS SQUIBB CO,DEPT MOLEC ONCOL & DRUG DEV,PRINCETON,NJ 08543. NR 59 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1996 VL 70 IS 8 BP 5503 EP 5510 PG 8 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200073 PM 8764062 ER PT J AU Spriggs, MK Armitage, RJ Comeau, MR Strockbine, L Farrah, T Macduff, B Ulrich, D Alderson, MR Mullberg, J Cohen, JI AF Spriggs, MK Armitage, RJ Comeau, MR Strockbine, L Farrah, T Macduff, B Ulrich, D Alderson, MR Mullberg, J Cohen, JI TI The extracellular domain of the Epstein-Barr virus BZLF2 protein binds the HLA-DR beta chain and inhibits antigen presentation SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN LYMPHOCYTES-B; GLYCOPROTEIN-H; C3D RECEPTOR; MONOCLONAL-ANTIBODY; CELLS; EXPRESSION; SEQUENCE; IDENTIFICATION; MOLECULES; REGION AB The Epstein-Barr virus BZLF2 gene encodes a glycoprotein that associates with gH and gL and facilitates the infection of B lymphocytes. In order to determine whether the BZLF2 protein recognizes a B-cell-specific surface antigen, a soluble protein containing the extracellular portion of the BZLF2 protein linked to the Fc portion of human immunoglobulin G1 (BZLF2.Fc) was expressed from mammalian cells. BZLF2.Fe was used in an expression cloning system and found to bind to a beta-chain allele of the HLA-DR locus of the class II major histocompatibility complex (MHC). Analysis of amino- and carboxy-terminal deletion mutants of the BZLF2.Fc protein indicated that the first 90 amino acids of BZLF2.Fc are not required for HLA-DR beta-chain recognition. Site-directed mutagenesis of an HLA-DR beta-chain cDNA and subsequent immunoprecipitation of expressed mutant beta-chain proteins using BZLF2.Fc indicated that the beta 1 domain, which participates in the formation of peptide binding pockets, is required for BZLF2.Fc recognition. The addition of BZLF2.Fc to sensitized peripheral blood mononuclear cells in vitro abolished their proliferative response to antigen and inhibited cytokine-dependent cytotoxic T-cell generation in mixed lymphocyte cultures. Flow-cytometric analysis of Akata cells induced to express late Epstein-Barr virus antigens indicated that expression of BZLF2 did not result in reduced surface expression levels of MHC class II. The ability of BZLF2.Fe to bind to the HLA-DR beta chain suggests that the BZLF2 protein may interact with MHC class II on the surfaces of B cells. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP Spriggs, MK (reprint author), IMMUNEX RES & DEV CORP,51 UNIV ST,SEATTLE,WA 98101, USA. NR 47 TC 91 Z9 92 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1996 VL 70 IS 8 BP 5557 EP 5563 PG 7 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200080 PM 8764069 ER PT J AU Neuveut, C Jeang, KT AF Neuveut, C Jeang, KT TI Recombinant human immunodeficiency virus type 1 genomes with tat unconstrained by overlapping reading frames reveal residues in Tat important for replication in tissue culture SO JOURNAL OF VIROLOGY LA English DT Article ID NEF GENE; MUTATIONAL ANALYSIS; KAPOSIS-SARCOMA; HIV-INFECTION; T-LYMPHOCYTES; GROWTH-FACTOR; CELL-LINE; PROTEIN; EXPRESSION; AIDS AB Human immunodeficiency virus type 1 (HIV-1) Tat is essential for virus replication and is a potent trans activator of viral gene expression. Evidence suggests that Tat also influences virus infectivity and cytopathicity. Extensive structure-function studies of Tat in subgenomic settings with point mutagenesis and transient transfection readouts have been performed. These reporter assays have defined certain amino acid residues as being important for trans activation of reporter plasmids. However, they have not directly addressed functions related to virus replication. Here, we have studied Tat structure-function in the setting of replicating viruses. We characterized mutations that emerged in Tat during HIV-1 infections of T lymphocytes. To ensure that the selection pressure for change was directed toward protein function, we constructed HIV-1s in which the Tat reading frame was freed from constraints exerted by overlapping with the reading frames of vpr, rev, and env. When these recombinant viruses were passaged in T cells, 26 novel nucleotide changes in tnt were observed from sequencing of 220 independently isolated clones. Recloning of these changes into a pNL4-3 molecular background allowed for the characterization of residues in Tat important for virus replication. Interestingly, many of the changes that affected replication when they were assayed in transient trans activation of plasmid reporters were found to be relatively neutral. We conclude that the structure-function of Tat in virus replication is incompletely reflected by activity measurements based only on subgenomic transient transfections. C1 NIAID,MOLEC MICROBIOL LAB,MOL VIROL SECT,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 70 TC 63 Z9 63 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1996 VL 70 IS 8 BP 5572 EP 5581 PG 10 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200082 PM 8764071 ER PT J AU Huang, JK Kwong, J Sun, ECY Liang, TJ AF Huang, JK Kwong, J Sun, ECY Liang, TJ TI Proteasome complex as a potential cellular target of hepatitis B virus X protein SO JOURNAL OF VIROLOGY LA English DT Article ID ANTIGEN PRESENTATION; MULTICATALYTIC PROTEINASE; TRANSACTIVATION FUNCTION; TRANSCRIPTION FACTOR; SEQUENCE-ANALYSIS; DNA-BINDING; GENE; EXPRESSION; MHC; DEGRADATION AB Although the biological importance of hepatitis B virus X protein (HBX) in the life cycle of hepatitis B virus has been well established, the cellular and molecular basis of its function remains largely undefined. Despite the association of multiple activities with HEX, none of them appear to provide a unifying hypothesis regarding the true biological function of HBX. Identification and characterization of cellular targets of HBX remain an essential goal in the elucidation of the molecular mechanisms of HBX. Using the Saccharomyces cerevisiae two-hybrid system, we have identified and characterized a novel subunit of the proteasome complex (XAPC7) that interacts specifically with HBX. We also showed that HEX binds specifically to XAPC7 in vitro. Mutagenesis studies have defined the domains of interaction to be critical for the function of HBX. Furthermore, overexpression of XAPC7 appeared to activate transcription by itself and antisense expression of XAPC7 was able to block transactivation by HBX. Therefore, the proteasome complex is possibly a functional target of HBX in cells. C1 NIDDK,NIH,LIVER DIS SECT,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA54524]; NIDDK NIH HHS [P30DK-43351, DK01952] NR 58 TC 134 Z9 143 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1996 VL 70 IS 8 BP 5582 EP 5591 PG 10 WC Virology SC Virology GA UX582 UT WOS:A1996UX58200083 PM 8764072 ER PT J AU Esposito, C Liu, ZH Striker, GE Phillips, C Chen, NY Chen, WY Kopchick, JJ Striker, LJ AF Esposito, C Liu, ZH Striker, GE Phillips, C Chen, NY Chen, WY Kopchick, JJ Striker, LJ TI Inhibition of diabetic nephropathy by a GH antagonist: A molecular analysis SO KIDNEY INTERNATIONAL LA English DT Article ID GROWTH-HORMONE RECEPTOR; GENE-EXPRESSION; TRANSGENIC MICE; BINDING-PROTEIN; FACTOR-BETA; MESSENGER-RNA; RENAL GROWTH; FACTOR-I; RATS; GLOMERULI AB Streptozotocin-treated C57B1/SJL mice developed glomerular hypertrophy and light microscopic lesions mimicking human diabetic glomerulosclerosis. In contrast, there were no glomerular hypertrophy and lesions in diabetic mice transgenic (TG) for a mutated growth hormone (bGH-G119K) that competes with native endogenous GH and results in dwarfism. We examined the molecular events underlying these findings. The non-transgenic (non-TG) diabetic mouse glomeruli had an increase in mRNA coding for alpha 1IV collagen, laminin B1, TGF-beta 1, 72 kDa collagenase, and TIMP-3. In contrast, glomerular type IV collagen and laminin B1 mRNA levels were normal in diabetic TG dwarf mice. However, the 72 kDa gelatinase, TIMP-3, and TGF-beta 1 mRNAs were elevated in the diabetic dwarfs. Type IV collagen and laminin accumulated in the glomeruli of diabetic non-TG, but not of diabetic dwarf mice, by immunofluorescence, microscopy, confirming the mRNA data. GH binding protein mRNA levels wee comparable in glomeruli from dwarf and non-TG mice, both diabetic and non-diabetic. We did not detect GH receptor mRNA in glomeruli. These data suggest that diabetic glomerulosclerosis is associated with an increase in type IV collagen and laminin synthesis, and that these changes do not occur in mice transgenic for bGH119K, a functional antagonist of GH. The increase of 72 kDa gelatinase, TIMP-3, and TGF-beta 1 mRNAs, independent of GH, suggested that these changes induced by hyperglycemia were not sufficient for the induction of glomerulosclerosis. C1 NIDDKD,RENAL CELL BIOL SECT,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. OHIO UNIV,MOLEC & CELLULAR BIOL PROGRAM,DEPT BIOL SCI,ATHENS,OH 45701. OHIO UNIV,EDISON BIOTECHNOL INST,ATHENS,OH 45701. OI Phillips, Carrie/0000-0002-0256-0736 FU PHS HHS [42137-01AZ] NR 46 TC 40 Z9 42 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 1996 VL 50 IS 2 BP 506 EP 514 DI 10.1038/ki.1996.342 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA UY726 UT WOS:A1996UY72600020 PM 8840279 ER PT J AU Bloembergen, WE Stannard, DC Port, FK Wolfe, RA Pugh, JA Jones, CA Greer, JW Golper, TA Held, PJ AF Bloembergen, WE Stannard, DC Port, FK Wolfe, RA Pugh, JA Jones, CA Greer, JW Golper, TA Held, PJ TI Relationship of dose of hemodialysis and cause-specific mortality SO KIDNEY INTERNATIONAL LA English DT Article ID ISCHEMIC-HEART-DISEASE; STAGE RENAL-DISEASE; ACCELERATED ATHEROSCLEROSIS; MAINTENANCE HEMODIALYSIS; DIALYSIS; MORBIDITY; SURVIVAL; MODELS; HYPERTENSION; PROFILES AB A number of studies have found a relationship of lower all-cause mortality risk for ESRD patients treated with increasing dose of dialysis. The objective of this study was to determine the relationship of delivered dose of dialysis with cause-specific mortality. Data from the USRDS Case Mix Adequacy Study, which includes a national random sample of hemodialysis patients, were utilized. To minimize the contribution of unmeasured residual renal function, the sample used in this analysis (N = 2479) included only patients on dialysis for one year or more. Cox proportional hazards models, stratified for diabetes, were used to analyze the effect of delivered dose of dialysis (measured and reported by both Kt/V and URR) on major causes of death and withdrawal from dialysis, adjusting for other covariates including demographics, comorbid diseases present at start of study, functional status, laboratory values and other dialysis parameters. Patient follow-up for mortality was censored at the earliest of time of transplantation, 60 days after a switch to peritoneal dialysis or at the time of data abstraction. For each 0.1 higher Kt/V, the adjusted relative risk of death due to coronary artery disease was 9% lower (RR = 0.91, P < 0.05), due to other cardiac causes was 12% lower (RR = 0.88, P < 0.01), due to cerebrovascular disease (CVD) was 14% lower (RR = 0.86, P < 0.05), due to infection was 9% lower (RR = 0.91, P = 0.05), and due to other known causes was 6% lower (RR = 0.94, P < 0.05). There was no statistically significant relationship of Kt/V and risk of death among patients who died of malignancy (RR = 0.84, P = 0.10) or among patients whose death cause was missing (RR = 0.95, P = 0.41). The risk of withdrawal from dialysis prior to death due to any cause was 9% lower (RR = 0.91, P < 0.05) for each 0.1 higher Kt/V. The relationships of delivered dose of dialysis, as measured by URR, and cause specific mortality were essentially similar in relative magnitude and statistical significance as the relationships observed using Kt/V as the measurement of dialysis dose, with the exception that the relationship was less significant for cerebrovascular disease and withdrawal from dialysis. The relationship of dialysis dose with risk of death due to each cause of death category except other cardiac causes and ''other'' causes appeared to be of greater magnitude and of greater statistical significance among diabetics than non-diabetics. These results indicate that low dose of dialysis is not associated with mortality due to just one isolated cause of death, but rather is due to a number of the major causes of death in this population. This study is consistent with hypotheses that low doses of dialysis may promote atherogenesis, infection, malnutrition and failure to thrive through a variety of pathophysiologic mechanisms. Further study is necessary to confirm these results and to test hypotheses that are developed. C1 UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT EPIDEMIOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT BIOSTAT,ANN ARBOR,MI 48109. UNIV TEXAS,DEPT MED,SAN ANTONIO,TX 78285. NIDDK,NIH,BETHESDA,MD. HLTH CARE FINANCING ADM,OFF RES & DEMONSTRAT,BALTIMORE,MD. UNIV ARKANSAS,DEPT INTERNAL MED,LITTLE ROCK,AR 72204. UNIV MICHIGAN,US RENAL DATA SYST,ANN ARBOR,MI 48109. OI Pugh, Jacqueline/0000-0003-4933-141X FU NIDDK NIH HHS [N01-DK-3-2202] NR 57 TC 113 Z9 115 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 1996 VL 50 IS 2 BP 557 EP 565 DI 10.1038/ki.1996.349 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA UY726 UT WOS:A1996UY72600027 PM 8840286 ER PT J AU Hakim, RM Held, PJ Stannard, DC Wolfe, RA Port, FK Daugirdas, JT Agodoa, L AF Hakim, RM Held, PJ Stannard, DC Wolfe, RA Port, FK Daugirdas, JT Agodoa, L TI Effect of the dialysis membrane on mortality of chronic hemodialysis patients SO KIDNEY INTERNATIONAL LA English DT Article ID BIOCOMPATIBILITY; MORBIDITY; SURVIVAL; INDEX AB Mortality of prevalent chronic hemodialysis patients remains high. The potential effect of the dialysis membrane on this mortality has not been previously investigated in a large population of chronic hemodialysis patients. Using data from the United States Renal Data System (USRDS), we analyzed a random sample of 6.536 patients receiving hemodialysis on December 31, 1990. The study design was a historical prospective study. By limiting the study to patients dialyzed for at least one year with bicarbonate dialysate, in whom the dose of dialysis could be calculated, and in whom dialysis membrane and co-existing morbidities were defined, the simple size was reduced to 2,410 patients. A Cox proportional hazards model was used to estimate relative mortality risk. The types of dialysis meinbranes used were broadly classified into three categories: unsubstituted cellulose, modified cellulose (generally cellulose membranes that have been modified by substitutions of some or most of their hydroxyl moieties) and synthetic membranes that are not cellulose-based. The results of the study suggest that after adjusting for the dose of dialysis and the presence of co-morbid factors, the relative risk of mortality of patients dialyzed with modified cellulose or synthetic membranes was at least 25% less than that of patients treated with unsubstituted cellulose membranes (P < 0.001). To account for the possibility that these differences were due to regional practice patterns, we further stratified the data for nine different regions. There was still a 20% difference in relative risk of mortality between membrane groups with the mortality statistically significant less in patients treated with synthetic membranes (P < 0.045) compared to patients dialyzed with unsubstituted cellulose membranes. The results of this study suggest that the dialysis membrane plays an important role in the outcome of chronic hemodialysis patients. However, more definitive studies are needed before a cause and effect relationship can be proven. C1 UNIV MICHIGAN,USRDS COORDINATING CTR,ANN ARBOR,MI 48109. WESTSIDE VA HOSP,DIV NEPHROL,CHICAGO,IL. NIDDK,NIH,BETHESDA,MD. RP Hakim, RM (reprint author), VANDERBILT UNIV,MED CTR,DIV NEPHROL,S-3307 MCN,NASHVILLE,TN 37232, USA. FU NHLBI NIH HHS [R01-HL36015]; NIDDK NIH HHS [N01-DK-32202] NR 21 TC 192 Z9 193 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 1996 VL 50 IS 2 BP 566 EP 570 DI 10.1038/ki.1996.350 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA UY726 UT WOS:A1996UY72600028 PM 8840287 ER PT J AU Weigler, BJ Thigpen, JE Goelz, MF Babineau, CA Forsythe, DB AF Weigler, BJ Thigpen, JE Goelz, MF Babineau, CA Forsythe, DB TI Randomly amplified polymorphic DNA polymerase chain reaction assay for molecular epidemiologic investigation of Pasteurella pneumotropica in laboratory rodent colonies SO LABORATORY ANIMAL SCIENCE LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; ARBITRARY PRIMERS; STRAINS; PCR; ANTIBODIES; ELISA; MICE; RECLASSIFICATION; DIFFERENTIATION; DIVERSITY AB After an episode of clinical Pasteurella pneumotropica infection was diagnosed in a C57BL/6N mouse, a randomly amplified polymorphic DNA polymerase chain reaction assay (RAPD-PCR) was developed and used to genetically characterize and differentiate 52 field isolates and laboratory reference strains of P. pneumotropica and related bacteria. A survey of rodents in the facility recovered 36 isolates of P. pneumotropica from 30 mice, six isolates from hamsters, and three isolates from rats during the follow-up investigation. Antibiograms and routine bacteriologic evaluations for morphologic and biochemical characteristics on selective media did not substantively aid in the differentiation of these isolates, but the RAPD-PCR revealed four strains of P. pneumotropica in the colony, two of which were confined to rats and hamsters. The RAPD-PCR unambiguously differentiated Heyl and Jawetz biotypes of P. pneumotropica recovered from mice, identified two additional genetic groups for rat and hamster isolates, and clearly distinguished P. pneumotropica from related bacteria. Most field isolates were genetically consistent with the Jawetz biotype of P. pneumotropica. The RAPD-PCR is a fast, sensitive, and efficient method for identifying genetic differences between strains of the P. pneumotropica complex and can contribute substantially in addressing the epidemiology, pathogenesis, and taxonomic classification of this common opportunistic pathogen. C1 NIEHS,COMPARAT MED BRANCH,RES TRIANGLE PK,NC 27709. RP Weigler, BJ (reprint author), N CAROLINA STATE UNIV,COLL VET MED,DEPT COMPAN ANIM & SPECIAL SPECIES MED,LAB ANIM RESOURCES,RALEIGH,NC 27606, USA. NR 49 TC 19 Z9 19 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD AUG PY 1996 VL 46 IS 4 BP 386 EP 392 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA VE739 UT WOS:A1996VE73900004 PM 8872988 ER PT J AU Bellahcene, A Antoine, N Clausse, N Tagliabue, E Fisher, LW Kerr, JM Jares, P Castronovo, V AF Bellahcene, A Antoine, N Clausse, N Tagliabue, E Fisher, LW Kerr, JM Jares, P Castronovo, V TI Detection of bone sialoprotein in human breast cancer tissue and cell lines at both protein and messenger ribonucleic acid levels SO LABORATORY INVESTIGATION LA English DT Article ID MATRIX PROTEIN; RNA EXPRESSION; LOCALIZATION; OSTEOPONTIN; OSTEOBLASTS; BSP; SITES AB The recent demonstration that bone sialoprotein (BSP) can be detected in human breast cancer tissue by immunoperoxidase suggests that this phosphoprotein is ectopically expressed by malignant mammary epithelial cells. Its detection in human breast cancer cells raises questions about its potential role(s) during breast cancer progression. Because BSP is secreted and is present in the serum, the positivity of breast cancer cells for BSP could have been the result of an uptake of the circulating phosphoprotein by the cells rather than of an intrinsic expression. We examined the expression of BSP at both the protein and mRNA levels in nine human breast cancer samples as well as in three human breast cancer cell lines (MCF-7, T47-D, and MDA-MB-231) using immunohistochemistry, flow cytometric analysis, immunoblot, and reverse-transcriptase PCR. BSP was detected at both protein and mRNA levels in human breast cancer tissue and in the three human breast cancer cell lines. Using a specific polyclonal anti-BSP antibody, we showed by both fluorescence-activated cell sorter analysis and immunohistochemistry experiments that all of the human breast cancer cell lines studied express BSP. This was localized at the cell surface and in the cytosol of the estrogen receptor-positive MCF-7 and T47-D cell lines, whereas it was detected only in the cytosol of the estrogen receptor-negative MDA-MB-231 cells. Using the same polyclonal anti-BSP antibody, we were able to identify an approximately 97-kd band on total protein extracts from the three cell lines by immunoblotting. Reverse-transcriptase PCR reactions using specific oligonucleotides performed on total RNA of nine human breast cancer biopsy samples and the three cell lines demonstrated the presence of BSP mRNA in all of the samples examined. This study is the first demonstration that human malignant breast epithelial cell lines express BSP at the protein and mRNA levels. Our study identified MCF-7, T47-D, and MDA-MB-231 cells as useful models for the examination of the molecular mechanisms involved in the ectopic expression of BSP in breast malignant lesions. C1 UNIV LIEGE,METASTASIS RES LAB,B-4000 SART,BELGIUM. IST NAZL TUMORI,I-20133 MILAN,ITALY. NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. PATHOL LAB,BARCELONA,SPAIN. RI Tagliabue, Elda/B-9377-2017 OI Tagliabue, Elda/0000-0001-9877-2903 NR 31 TC 41 Z9 42 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD AUG PY 1996 VL 75 IS 2 BP 203 EP 210 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA VC435 UT WOS:A1996VC43500008 PM 8765320 ER PT J AU Otsuki, T Kumar, S Ensoli, B Kingma, DW Yano, T StetlerStevenson, M Jaffe, ES Raffeld, M AF Otsuki, T Kumar, S Ensoli, B Kingma, DW Yano, T StetlerStevenson, M Jaffe, ES Raffeld, M TI Detection of HHV-8/KSHV DNA sequences in AIDS-associated extranodal lymphoid malignancies SO LEUKEMIA LA English DT Article DE HHV-8/KSHV; AIDS; non-Hodgkin's lymphoma; extranodal lymphoma ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; CELL AB Herpesvirus-like DNA sequences have been identified in a high proportion of both AIDS-associated and classical Kaposi's sarcoma, and in a small percentage of AIDS-associated malignant lymphomas. To determine the extent of involvement of this new agent designated HHV-8 (human herpesvirus type 8) or KSHV (Kaposi's sarcoma-associated herpesvirus) in human malignant lymphomas, we analyzed 24 AIDS-associated lymphoid malignancies and 100 non-AIDS-associated lymphomas by PCR and Southern blot analysis. Three of 24 lymphoid malignancies from patients with AIDS demonstrated HHV-8 sequences by Southern blot and PCR analyses. The fourth was positive by PCR only. None of the non-AIDS-associated lymphomas contained HHV-8 sequences. All three Southern blot positive samples were derived from extranodal regions, two from pleural effusions, and one from a soft tissue mass in the thigh. This latter patient initially presented with a pleural effusion. The fourth PCR positive but Southern blot negative tumor was from a gingival lymphoma in a patient with a history of Kaposi's sarcoma. All tumors positive for HHV-8 were also positive for EBV. These results confirm a recent report that this novel herpesvirus may play a role in AIDS-associated lymphomas, especially in those with body cavity presentation. C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 17 TC 87 Z9 87 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 1996 VL 10 IS 8 BP 1358 EP 1362 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA VA644 UT WOS:A1996VA64400016 PM 8709643 ER PT J AU Worobec, AS Kirshenbaum, AS Schwartz, LB Metcalfe, DD AF Worobec, AS Kirshenbaum, AS Schwartz, LB Metcalfe, DD TI Treatment of three patients with systemic mastocytosis with interferon alpha-2b SO LEUKEMIA & LYMPHOMA LA English DT Article DE interferon alpha; treatment; mastocytosis ID ACTIVATED PROTEIN-KINASE; CHRONIC MYELOID-LEUKEMIA; CELL-PROLIFERATION; MAST-CELLS; GENES; SYNTHETASE; PROGNOSIS; DISEASE; BLOOD AB It has been reported that the administration of interferon alpha-2b is of potential benefit in the treatment of mastocytosis based on a single patient study (NEJM, Feb 27, 1992, 326(9):619-623). Following this report, we administered interferon alpha-2b at a dose of 4 to 5 million units per square meter of body surface area for at least 12 months to one patient with mastocytosis with an associated hematologic disorder (patient 1), one patient with aggressive systemic mastocytosis (patient 2), and one patient with indolent mastocytosis (patient 3). Patients were monitored with the following clinical and laboratory parameters: serial bone marrow biopsies and aspirates, patient log of histamine release attacks, medication dependency, plasma tryptase levels. serum lactate dehydrogenase (LDH) levels, white blood cell counts and differentials, extent of urticaria pigmentosa lesions, bony involvement, and extent of gastrointestinal involvement and hepatomegaly. We also examined the ability of interferon alpha-2b to inhibit recombinant human stem cell factor (rhSCF)-dependent mast cell proliferation from CD34+ bone marrow-derived cells. All patients demonstrated continued progression of disease in one or more clinical criteria at one year of therapy. Similarly, interferon alpha-2b did not inhibit the culture of mast cells from CD34+ bone marrow-derived cells in the presence of SCF. Thus, in our study of three patients with systemic mastocytosis, treatment with interferon alpha-2b was found to be ineffective in controlling progression of disease. RP Worobec, AS (reprint author), NIAID,LAB ALLERG DIS,NIH,BLDG 10,ROOM 11C210,10 CTR DR MSC 1888,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI20487] NR 40 TC 72 Z9 74 U1 0 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD AUG PY 1996 VL 22 IS 5-6 BP 501 EP 508 DI 10.3109/10428199609054789 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA VG827 UT WOS:A1996VG82700016 PM 8882964 ER PT J AU Ye, FQ Pekar, JJ Jezzard, P Duyn, T Frank, JA McLaughlin, AC AF Ye, FQ Pekar, JJ Jezzard, P Duyn, T Frank, JA McLaughlin, AC TI Perfusion imaging of the human brain at 1.5T using a single-shot EPI spin tagging approach SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cerebral blood flow; perfusion; human; brain ID CEREBRAL BLOOD-FLOW; ARTERIAL WATER; INVERSION; SATURATION AB Single-shot echo planar imaging (EPI) techniques have been applied, in conjunction with arterial spin tagging approaches, to obtain images of cerebral blood flow in a single axial slice in the human brain. Serial studies demonstrate that cerebral blood flow images acquired in 8 min are reproducible, with a statistical precision of approximately +/-10 cc/100 g/min. The average value of cerebral blood flow in the slice is 51 +/- 11 cc/100 g/min for six normal subjects. The cerebral blood flow images contain two types of artifact, probably due to arterial and venous blood volume contributions, which must be overcome before the arterial spin tagging approach can be used for routine clinical studies. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NIMH,PSYCHOL & PSYCHOPATHOL LAB,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,INST COGNIT & COMPUTAT SCI,WASHINGTON,DC 20007. NIH,LAB DIAGNOST RADIOL RES,OIR,BETHESDA,MD 20892. OI Jezzard, Peter/0000-0001-7912-2251 NR 26 TC 33 Z9 33 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD AUG PY 1996 VL 36 IS 2 BP 219 EP 224 DI 10.1002/mrm.1910360208 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VA984 UT WOS:A1996VA98400007 ER PT J AU Horska, A Spencer, RGS AF Horska, A Spencer, RGS TI Measurement of spin-lattice relaxation times and kinetic rate constants in rat muscle using progressive partial saturation and steady-state saturation transfer SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE NMR; spin-lattice relaxation time; creatine kinase; muscle ID NUCLEAR MAGNETIC-RESONANCE; P-31 NMR-SPECTRA; CREATINE-KINASE; SKELETAL-MUSCLE; CHEMICAL-EXCHANGE; HUMAN FOREARM; HUMAN BRAIN; HEART; INVIVO; SPECTROSCOPY AB P-31 spin-lattice relaxation times (T-1) of metabolites in rat calf muscle at 1.9 Tesla and the forward rate through the creatine kinase (CK) reaction have been measured using a new method based on modeling progressive saturation explicitly incorporating the effect of chemical exchange. In a separate series of experiments, we compared our method with inversion recovery both in vitro and in vivo, finding agreement between the techniques. We found that the T-1 values of phosphocreatine (PCr) (6.6 +/- 0.3 s), gamma-ATP (2.6 +/- 0.6 s), alpha-ATP (2.4 +/- 0.4 s) and beta-ATP (2.2 +/- 0.2 s) are unchanged by stimulation of sufficient intensity to induce a 32% drop in PCr level. The errors in T-1 values which arise when chemical exchange is neglected are calculated. These are found to be on the order of 20% for PCr and 30-50% for gamma-ATP under typical conditions. Use of longer repetition times results in larger errors in measured values of T-1. This source of error can be effectively eliminated by use of sufficiently short repetition times. We found that the rate constant of the forward CK reaction was increased 60% by stimulation, from 0.20 +/- 0.03 s(-1) to 0.32 +/- 0.03 s(-1), but that the phosphorus flux did not change. C1 NIA,NIH,BALTIMORE,MD 21224. INST CLIN & EXPTL MED,PRAGUE,CZECH REPUBLIC. NR 36 TC 20 Z9 20 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD AUG PY 1996 VL 36 IS 2 BP 232 EP 240 DI 10.1002/mrm.1910360210 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VA984 UT WOS:A1996VA98400009 ER PT J AU Liao, X Gilbert, DJ Dent, A Staudt, LM Jenkins, NA Copeland, NG AF Liao, X Gilbert, DJ Dent, A Staudt, LM Jenkins, NA Copeland, NG TI Mapping of the mouse Bcl6 gene to Chromosome 16 SO MAMMALIAN GENOME LA English DT Article ID FINGER ENCODING GENE; CELL LYMPHOMA; TRANSLOCATIONS C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NCI,METAB BRANCH,BETHESDA,MD 20892. NR 14 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD AUG PY 1996 VL 7 IS 8 BP 621 EP 622 DI 10.1007/s003359900185 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VB927 UT WOS:A1996VB92700017 PM 8678989 ER PT J AU Xue, J Jenkins, NA Gilbert, DJ Copeland, NG Sadler, JE AF Xue, J Jenkins, NA Gilbert, DJ Copeland, NG Sadler, JE TI Structure and localization of the thrombin receptor gene on mouse Chromosome 13 SO MAMMALIAN GENOME LA English DT Article ID PROTEINASE-ACTIVATED RECEPTOR-2; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; LINKAGE MAP; CDNA C1 WASHINGTON UNIV,SCH MED,DEPT MED,HOWARD HUGHES MED INST,DEPT BIOCHEM & MOL BIOPHYS,ST LOUIS,MO 63110. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Sadler, Evan/D-8556-2011 FU NHLBI NIH HHS [HL14147] NR 13 TC 0 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD AUG PY 1996 VL 7 IS 8 BP 625 EP 626 DI 10.1007/s003359900189 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VB927 UT WOS:A1996VB92700021 PM 8678993 ER PT J AU Taylor, BA Grieco, D Kohn, LD AF Taylor, BA Grieco, D Kohn, LD TI Localization of gene encoding the thyroid stimulating hormone receptor (Tshr) on mouse Chromosome 12 SO MAMMALIAN GENOME LA English DT Article ID HUMAN THYROTROPIN RECEPTOR; MOLECULAR-CLONING; EXPRESSION; AUTOANTIBODIES; PROTEIN; MICE C1 NIDDK,NIH,BETHESDA,MD 20892. RP Taylor, BA (reprint author), JACKSON LAB,600 MAIN ST,BAR HARBOR,ME 04609, USA. FU NIGMS NIH HHS [GM18684] NR 18 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD AUG PY 1996 VL 7 IS 8 BP 626 EP 628 DI 10.1007/s003359900190 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VB927 UT WOS:A1996VB92700022 PM 8678994 ER PT J AU Zimonjic, DB Popescu, NC Brown, PC Silverman, JA AF Zimonjic, DB Popescu, NC Brown, PC Silverman, JA TI Localization of rat Pgy3 (mdr2) to the same region as Pgy2 (mdr1b) at 4q11-12 SO MAMMALIAN GENOME LA English DT Article ID P-GLYCOPROTEIN GENE; INSITU HYBRIDIZATION; CLONING; LOCUS C1 NCI,EXPT CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,BIOL LAB,BETHESDA,MD 20892. NR 8 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD AUG PY 1996 VL 7 IS 8 BP 630 EP 631 DI 10.1007/s003359900295 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VB927 UT WOS:A1996VB92700026 PM 8679007 ER PT J AU Mock, BA Coleman, MP Huang, S AF Mock, BA Coleman, MP Huang, S TI Riz maps to distal Chromosome 4 near genes involved in tumorigenesis and nerve degeneration SO MAMMALIAN GENOME LA English DT Article ID MOUSE CHROMOSOME-4; PROTEIN C1 DEPT PHARMACOL,OXFORD OX1 3QT,ENGLAND. BURNHAM INST,BURNHAM CTR,LA JOLLA CANC RES CTR,LA JOLLA,CA 92037. RP Mock, BA (reprint author), NCI,NIH,BLDG 37,ROOM 2B08,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA57496, N01-BC-21075] NR 14 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD AUG PY 1996 VL 7 IS 8 BP 637 EP 637 DI 10.1007/s003359900195 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VB927 UT WOS:A1996VB92700032 PM 8679000 ER PT J AU Riley, GF Feuer, EJ Lubitz, JD AF Riley, GF Feuer, EJ Lubitz, JD TI Disenrollment of Medicare cancer patients from health maintenance organizations SO MEDICAL CARE LA English DT Article DE disenrollment; cancer; health maintenance organizations; access; quality; satisfaction ID GRAPHICAL REPRESENTATION; MORTALITY-RATES; SURVIVAL AB OBJECTIVES. There is concern that financial incentives in health maintenance organizations (HMOs) might result in pressures to induce sicker members to disenroll. The authors compared disenrollment rates of Medicare HMO enrollees with cancer with disenrollment rates for cancer-free enrollees, using Medicare enrollment files linked to population-based tumor registry data from the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS. The authors identified all aged Medicare beneficiaries who enrolled in an HMO located in a SEER reporting area during 1985 to 1989. Time to disenrollment was analyzed using a proportional hazards model. RESULTS. Overall, cancer patients were no more likely to disenroll than others. However, persons diagnosed with cancer after enrollment were less likely to disenroll. than other persons in Independent practice Association (IPA) model HMOs (relative risk [RR] = 0.79). Persons diagnosed with cancer after enrollment in group- and staff-model HMOs were about equally likely to disenroll as other persons (RR = 0.91). Persons diagnosed with cancer less than 18 months before enrollment were at high risk for disenrollment from both IPA and group-/staff-model HMOs (RR = 1.47 and 1.35). There was substantial variation among HMOs in overall disenrollment rates and in RRs for disenrollment by cancer patients. CONCLUSIONS. The low disenrollment rates of patients diagnosed after enrollment do not support the contention that features intrinsic to managed care make HMOs unattractive to the seriously ill. Monitoring of selective disenrollment could be used as a screen for possible access and quality problems. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP Riley, GF (reprint author), US HLTH CARE FINANCING ADM,OFF RES & DEMONSTRAT,7500 SECUR BLVD,C-3-24-07,BALTIMORE,MD 21244, USA. NR 20 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1996 VL 34 IS 8 BP 826 EP 836 DI 10.1097/00005650-199608000-00009 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VB193 UT WOS:A1996VB19300009 PM 8709663 ER PT J AU Zhang, SQ Douglas, MA Yaroslavsky, L Summers, RM Dilsizian, V Fananapazir, L Bacharach, SL AF Zhang, SQ Douglas, MA Yaroslavsky, L Summers, RM Dilsizian, V Fananapazir, L Bacharach, SL TI A Fourier based algorithm for tracking SPAMM tags in gated magnetic resonance cardiac images SO MEDICAL PHYSICS LA English DT Article ID MOTION AB A method is described for automatically tracking spatial modulation of magnetization tag lines on gated cardiac images. The method differs from previously reported methods in that it uses Fourier based spatial frequency and phase information to separately track horizontal and vertical tag lines. Use of global information from the frequency spectrum of an entire set of tag lines was hypothesized to result in a robust algorithm with decreased sensitivity to noise. The method was validated in several ways: first, actual tagged cardiac images at end diastole were deformed known amounts, and the algorithm's predictions compared to the known deformations. Second, tagged, gated images of the thigh muscle (assumed to have similar signal to noise characteristics as cardiac images, but to not deform with time) were created. Again the algorithmic predictions could be compared to the known (zero magnitude) deformations and to thigh images which had been artificially deformed. Finally, actual cardiac tagged images were acquired, and comparisons made between manual, visual, determinations of tag line locations, and those predicted by the algorithm. At 0.5 T, the mean bias of the method was <0.34 mm even at large deformations and at late (noisy) times. The standard deviation of the method, estimated from the tagged thigh images, was <0.7 mm even at late times. The method may be expected to have even lower error at higher field strengths. RP Zhang, SQ (reprint author), NIH, BLDG 10, RM 1C401, 10 CTR DR, BETHESDA, MD 20892 USA. NR 13 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 1996 VL 23 IS 8 BP 1359 EP 1369 DI 10.1118/1.597819 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VC624 UT WOS:A1996VC62400006 PM 8873033 ER PT J AU Gallagher, D Visser, M Wang, ZM Harris, T Pierson, RN Heymsfield, SB AF Gallagher, D Visser, M Wang, ZM Harris, T Pierson, RN Heymsfield, SB TI Metabolically active component of fat-free body mass: Influences of age, adiposity, and gender SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DUAL-PHOTON ABSORPTIOMETRY; RELATIVE EXPANSION; ENERGY-EXPENDITURE; SKELETAL-MUSCLE; CELL MASS; POTASSIUM; WOMEN; ADULTS; GD-153; MODEL AB Fat-free body mass (FFM) is often considered the metabolically active compartment and is widely used to adjust between-subject differences in resting energy expenditure for body composition. The use of FFM as the metabolically active portion of body weight makes the assumption that the body cell mass (BCM) component which is more difficult to measure, maintains a relatively constant relationship to FFM within and between subjects. The aim of this study was to test the hypothesis that BCM and FFM are associated independently of age, adiposity (as represented by body density), and gender in healthy white women and men. BCM and FFM were, estimated by whole-body K-40-counting and dual-energy x-ray absorptiometry (DXA), respectively. Multiple regression analysis was used to model the relationships between BCM as the dependent variable and FFM, age, body density, and gender as potential independent variables. FFM alone explained 51% and 63% of between-individual BCM differences in women (n = 269) and men (n = 204) (both P = .0001), respectively. Age contributed significantly (P = .0001) to BCM prediction after adjusting first for FFM in both women and men, Body density also added significantly (P = .004 and P = .0001) to FFM and age prediction of BCM in women and men, respectively. Lastly, gender contributed significantly to the composite model, with 91% of between-individual differences in BCM explained by FFM, age, body density, and gender. Hence, BCM does not maintain a fixed relationship to FFM, as often assumed, but varies significantly and independently of FFM with age, adiposity, and gender. These findings Rave implications for the study of metabolic indices such as resting energy expenditure. Copyright (C) 1996 by W.B. Saunders Company C1 COLUMBIA UNIV COLL PHYS & SURG, ST LUKES ROOSEVELT HOSP, OBES RES CTR, NEW YORK, NY USA. AGR UNIV WAGENINGEN, DEPT HUMAN NUTR, WAGENINGEN, NETHERLANDS. NIA, EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. OI Gallagher, Dympna/0000-0003-1769-9754 FU NIA NIH HHS [R01-AG13021] NR 35 TC 35 Z9 35 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 1996 VL 45 IS 8 BP 992 EP 997 DI 10.1016/S0026-0495(96)90269-3 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VD573 UT WOS:A1996VD57300014 PM 8769358 ER PT J AU Zhuang, ZP Gnarra, JR Dudley, CF Zbar, B Linehan, WM Lubensky, IA AF Zhuang, ZP Gnarra, JR Dudley, CF Zbar, B Linehan, WM Lubensky, IA TI Detection of von Hippel-Lindau disease gene mutations in paraffin-embedded sporadic renal cell carcinoma specimens SO MODERN PATHOLOGY LA English DT Article DE mutations; oncocytoma; paraffin embedded; renal cell carcinoma; SSCP; vonHippel-Lindau disease gene ID STRAND CONFORMATION POLYMORPHISM; TUMOR-SUPPRESSOR GENE; MOLECULAR ANALYSIS; SHORT ARM; P53 GENE; DNA; ONCOCYTOMA; CHROMOSOME-3 AB The von Hippel-Lindau (VHL) disease gene on chromosome 3p25.5 has been cloned and shown to be mutated in the germline DNA of patients with VHL disease. In addition, approximately 60% of sporadic renal cell carcinomas (RCCs) have been shown to have a VHL gene mutation in fresh frozen tumor tissue and tumor-derived cell lines, The objective of this study was to test whether VHL gene mutations could be detected in archival sporadic RCC cases. We studied three sporadic RCCs, two oncocytomas, and the corresponding adjacent normal renal parenchyma by polymerase chain reaction and single-strand conformation polymorphism analysis using paraffin-embedded, formalin-fixed material, Tumor and normal tissue were microdissected from eosin-stained 5-mu m-thick histologic sections, Mutations in exon 2 of the VHL gene were detected in all three of the sporadic RCCs but were not observed in the matched normal renal tissues or in the true oncocytomas tested. The mutations were identical to those detected in tumor cell Lines from the same patients. This report represents the first detection of VHL gene mutations in sporadic RCCs in archival, paraffin-embedded tissue. A high percentage of sporadic RCCs show VHL gene mutations in fresh frozen tissue but the availability of frozen material is limited, so the evaluation of archival tumors for similar mutations should prove useful in future RCC studies. Furthermore, the results suggest that the genetic events leading to the development of clinically benign renal oncocytoma may differ from those leading to malignant RCC. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. NR 22 TC 27 Z9 28 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD AUG PY 1996 VL 9 IS 8 BP 838 EP 842 PG 5 WC Pathology SC Pathology GA VC628 UT WOS:A1996VC62800006 PM 8871925 ER PT J AU Henson, DE AF Henson, DE TI Is the meaning of science changing in the practice of medicine? - Reply SO MODERN PATHOLOGY LA English DT Letter RP Henson, DE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD AUG PY 1996 VL 9 IS 8 BP 872 EP 872 PG 1 WC Pathology SC Pathology GA VC628 UT WOS:A1996VC62800019 ER PT J AU Ma, D Hong, XQ Raghavan, N Scott, AL McCarthy, JS Nutman, TB Williams, SA Carlow, CKS AF Ma, D Hong, XQ Raghavan, N Scott, AL McCarthy, JS Nutman, TB Williams, SA Carlow, CKS TI A cyclosporin A-sensitive small molecular weight cyclophilin of filarial parasites SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Brugia malayi; Onchocerca volvulus; Dirofilaria immitis; cyclophilin; peptidyl-prolyl cis-trans isomerase; Cyclosporin A ID NEMATODE BRUGIA-MALAYI; CIS-TRANS-ISOMERASE; TOXOPLASMA-GONDII; PROTEIN; SEQUENCE; HOMOLOG C1 NEW ENGLAND BIOLABS INC,BEVERLY,MA 01915. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. SMITH COLL,DEPT BIOL SCI,NORTHAMPTON,MA 01063. NR 35 TC 22 Z9 22 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD AUG PY 1996 VL 79 IS 2 BP 235 EP 241 DI 10.1016/0166-6851(96)02654-0 PG 7 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VA641 UT WOS:A1996VA64100011 PM 8855561 ER PT J AU Moore, TA Ramachandran, S Gam, AA Neva, FA Lu, WH Saunders, L Williams, SA Nutman, TB AF Moore, TA Ramachandran, S Gam, AA Neva, FA Lu, WH Saunders, L Williams, SA Nutman, TB TI Identification of novel sequences and codon usage in Strongyloides stercoralis SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Strongyloides stercoralis; cDNA libraries ID GENE C1 SMITH COLL, CLARK SCI CTR, DEPT BIOL SCI, NORTHAMPTON, MA 01063 USA. RP NIAID, PARASIT DIS LAB,NIH,BLDG 4,ROOM 126, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 8 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 EI 1872-9428 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD AUG PY 1996 VL 79 IS 2 BP 243 EP 248 DI 10.1016/0166-6851(96)02659-X PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VA641 UT WOS:A1996VA64100012 PM 8855562 ER PT J AU Myers, MG Zhang, YT Aldaz, GAI Grammer, T Glasheen, EM Yenush, L Wang, LM Sun, XJ Blenis, J Pierce, JH White, MF AF Myers, MG Zhang, YT Aldaz, GAI Grammer, T Glasheen, EM Yenush, L Wang, LM Sun, XJ Blenis, J Pierce, JH White, MF TI YMXM motifs and signaling by an insulin receptor substrate 1 molecule without tyrosine phosphorylation sites SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; S6 KINASE; IRS-1; ACTIVATION; STIMULATION; PHOSPHOTYROSINE; 3'-KINASE; DOMAINS; CELLS AB Tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) by the activated receptors for insulin, IGF-1, and various cytokines creates binding sites for signaling proteins with Src homology 2 domains (SH2 proteins). Determining the role of specific SH2 proteins during insulin signaling has been difficult because IRS-1 possesses as many as 18 potential tyrosine phosphorylation sites, several of which contain redundant motifs. Using 32D cells, which contain no endogenous IRS proteins, we compared the signaling ability of an IRS-1 molecule in which 18 potential tyrosine phosphorylation sites were replaced by phenylalanine (IRS-1(F18))) with two derivative molecules which retained three YMXM motifs (IRS-1(3YMXM)) or the two COOH-terminal SHP2-Fyn binding sites (IRS-1(YCT)). During insulin stimulation, IRS-1(F18) failed to undergo tyrosine phosphorylation or mediate activation of the phosphotidylinositol (PI) 3'-kinase or p70(s6k); IRS-1(YCT) was tyrosine phosphorylated but also failed to mediate these signaling events. Neither IRS-1(3YMXM) nor IRS-1(YCT) mediated activation of mitogen-activated protein kinases. IRS-1(F18) and IRS-1(YCT) partially mediated similar levels of insulin-stimulated mitogenesis at high insulin concentrations, however, suggesting that IRS-1 contains phosphotyrosine-independent elements which effect mitogenic signals, and that the sites in IRS-1(YCT) do not augment this signal. IRS-1(3YMXM) mediated the maximal mitogenic response to insulin, although the response to insulin was more sensitive with wild-type IRS-1. By contrast, the association of IRS-1(3YMXM) with PI 3'-kinase was more sensitive to insulin than the association with IRS-1. Thus, the binding of SH2 proteins (such as PI 3'-kinase) by YMXM moths in IRS-1 is an important element in the mitogenic response, but other elements are essential for full mitogenic sensitivity. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NIH,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NCI NIH HHS [CA 46595]; NIDDK NIH HHS [DK 38712, DK 43808] NR 56 TC 69 Z9 69 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1996 VL 16 IS 8 BP 4147 EP 4155 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY025 UT WOS:A1996UY02500018 PM 8754813 ER PT J AU Kim, MK LesoonWood, LA Weintraub, BD Chung, JH AF Kim, MK LesoonWood, LA Weintraub, BD Chung, JH TI A soluble transcription factor, Oct-1, is also found in the insoluble nuclear matrix and possesses silencing activity in its alanine-rich domain SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID THYROTROPIN-BETA-GENE; POU-SPECIFIC DOMAIN; SCAFFOLD-ASSOCIATED REGIONS; OCTAMER-BINDING-PROTEINS; DNA-BINDING; THYROID-HORMONE; SUBUNIT GENE; ANTERIOR-PITUITARY; ACTIVATION DOMAINS; SENSITIVE REGIONS AB Expression of the human thyrotropin beta (hTSH beta) gene is restricted to thyrotrophs, at least in part, by silencing, Using transient-transfection assays, we have localized a silencer element to a region between -128 and -480 bp upstream of the transcription initiation site. The silencing activity was overcome in a thyrotroph-specific manner by an unknown enhancer located in the sequences at -similar to 10000 to -1200 bp. The ubiquitous POU homeodomain protein Oct-1 recognized the A/T-rich silencer element at multiple sites in gel mobility shift assays and in vitro footprinting analyses. The silencing activity of Oct-1 was localized in its C-terminal alanine-rich domain, suggesting that Oct-1 plays a role in silencing of the hTSH beta promoter, Further, a significant fraction of Oct-1 was shown to be associated with the nuclear matrix, and the hTSH beta silencer region was tethered to a nuclear matrix of human cells in vivo, suggesting a possible role of the Oct-1-hTSH beta silencer region interaction in chromatin organization. C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. RP Kim, MK (reprint author), NIDDK,NIH,MOL & CELLULAR ENDOCRINOL BRANCH,BLDG 10,ROOM 8D14,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 75 TC 78 Z9 78 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1996 VL 16 IS 8 BP 4366 EP 4377 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY025 UT WOS:A1996UY02500042 PM 8754837 ER PT J AU Bennett, CB Westmoreland, TJ Snipe, JR Resnick, MA AF Bennett, CB Westmoreland, TJ Snipe, JR Resnick, MA TI A double-strand break within a yeast artificial chromosome (YAC) containing human DNA can result in YAC loss, deletion, or cell lethality SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CYCLE ARREST; RAD9 GENE; REPAIR; TRANSFORMATION; RECOMBINATION; DAMAGE; SEQUENCE; HOMOLOGY; SYSTEM AB Human chromosomal DNA contains many repeats which might provide opportunities for DNA repair. We have examined the consequences of a single double-strand break (DSB) within a 360-kb dispensable yeast artificial chromosome (YAC) containing human DNA (YAC12), An Alu-UR43-YZ sequence was targeted to several Alu sites within the YAC in strains of the yeast Saccharomyces cerevisiae; the strains contained a galactose-inducible HO endonuclease that cut the YAC at the YZ site, The presence of a DSB in most YACs led to deletion of the URA3 cassette, with retention of the telomeric markers, through recombination between surrounding Alus. For two YACs, the DSBs were not repaired and there was a G(2) delay associated with the persistent DSBs. The presence of persistent DSBs resulted in cell death even though the YACs were dispensable. Among the survivors of the persistent DSBs, most had lost the YAC. By a pullback procedure, cell death was observed to begin at least 6 h after induction of a break, For YACs in which the DSB was rapidly repaired, the breaks did not cause cell cycle delay or lead to cell death. These results are consistent with our previous Conclusion that a persistent DSB in a plasmid (YZ-CEN) also caused lethality (C. B. Bennett, A. L. Lewis, K. K. Baldwin, and M. A. Resnick, Proc. Natl, Acad. Sci. USA 90:5613-5617, 1993). However, a break in the YZ-CEN plasmid did not induce lethality in the strain (CBY) background used in the present study, The differences in survival levels appear to be due to the rapid degradation of the plasmid in the CBY strain. We, therefore, propose that for a DSB to cause cell cycle delay and death by means other than the loss of essential genetic material, it must remain unrepaired and be long-lived. RP Bennett, CB (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 39 Z9 40 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1996 VL 16 IS 8 BP 4414 EP 4425 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY025 UT WOS:A1996UY02500047 PM 8754842 ER PT J AU McGrew, MJ Bogdanova, N Hasegawa, K Hughes, SH Kitsis, RN Rosenthal, N AF McGrew, MJ Bogdanova, N Hasegawa, K Hughes, SH Kitsis, RN Rosenthal, N TI Distinct gene expression patterns in skeletal and cardiac muscle are dependent on common regulatory sequences in the MLC1/3 locus SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEAVY-CHAIN GENE; ENHANCER-BINDING FACTOR; LIGATION-MEDIATED PCR; TRANSCRIPTION FACTOR GATA-4; ALPHA-ACTIN PROMOTER; MYOSIN LIGHT CHAIN-1; TRANSGENIC MICE; CHLORAMPHENICOL ACETYLTRANSFERASE; MYOCARDIAL-CELLS; MOUSE EMBRYO AB The myosin light-chain 1/3 locus (MLC1/3) is regulated by two promoters and a downstream enhancer element which produce two protein isoforms in fast skeletal muscle at distinct stages of mouse embryogenesis. We have analyzed the expression of transcripts from the internal MLC3 promoter and determined that it is also expressed in the atria of the heart. Expression from the MLC3 promoter in these striated muscle lineages is differentially regulated during development. In transgenic mice, the MLC3 promoter is responsible for cardiac-specific reporter gene expression while the downstream enhancer augments expression in skeletal muscle. Examination of the methylation status of endogenous and transgenic promoter and enhancer elements indicates that the internal promoter is not regulated in a manner similar to that of the MLC1 promoter or the downstream enhancer. A GATA protein consensus sequence in the proximal MLC3 promoter but not the MLC1 promoter binds with high affinity to GATA-4, a cardiac muscle- and gut-specific transcription factor. Mutation of either the MEF2 or GATA motifs in the MLC3 promoter attenuates its activity in both heart and skeletal muscles, demonstrating that MLC3 expression in these two diverse muscle types is dependent on common regulatory elements. C1 MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED CARDIOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT CELL BIOL,BRONX,NY 10461. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NHLBI NIH HHS [HL02699]; NIAMS NIH HHS [R01AR41926] NR 76 TC 56 Z9 57 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1996 VL 16 IS 8 BP 4524 EP 4534 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY025 UT WOS:A1996UY02500058 PM 8754853 ER PT J AU Kitareewan, S Burka, LT Tomer, KB Parker, CE Deterding, LJ Stevens, RD Forman, BM Mais, DE Heyman, RA McMorris, T Weinberger, C AF Kitareewan, S Burka, LT Tomer, KB Parker, CE Deterding, LJ Stevens, RD Forman, BM Mais, DE Heyman, RA McMorris, T Weinberger, C TI Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID RETINOID-X-RECEPTOR; HUMAN GLUCOCORTICOID RECEPTOR; THYROID-HORMONE; ACID RECEPTOR; LIQUID-CHROMATOGRAPHY; TRANSCRIPTION FACTOR; 9-CIS-RETINOIC ACID; RESPONSE PATHWAYS; ECDYSONE RECEPTOR; FATTY-ACIDS AB RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional activity. Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 mu M. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytenic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced [H-3]-9cRA from RXR with K-i values of 4 mu M, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effecters, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signaling pathways. C1 NIEHS,ORPHAN RECEPTOR GRP,RES TRIANGLE PK,NC 27709. NIEHS,CHEM METAB & TOXICOKINET GRP,RES TRIANGLE PK,NC 27709. NIEHS,MASS SPECTROMETRY GRP,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT PEDIAT,DIV MED GENET,MASS SPECTROMETRY FACIL,DURHAM,NC 27710. SALK INST BIOL STUDIES,GENE EXPRESS LAB,LA JOLLA,CA 92037. LIGAND PHARMACEUT INC,SAN DIEGO,CA 92121. UNIV CALIF SAN DIEGO,DEPT CHEM,LA JOLLA,CA 92037. RI Tomer, Kenneth/E-8018-2013 NR 87 TC 118 Z9 123 U1 2 U2 4 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD AUG PY 1996 VL 7 IS 8 BP 1153 EP 1166 PG 14 WC Cell Biology SC Cell Biology GA VB774 UT WOS:A1996VB77400001 PM 8856661 ER PT J AU Knuckey, NW Finch, P Palm, DE PRimiano, MJ Johanson, CE Flanders, KC Thompson, NL AF Knuckey, NW Finch, P Palm, DE PRimiano, MJ Johanson, CE Flanders, KC Thompson, NL TI Differential neuronal and astrocytic expression of transforming growth factor beta isoforms in rat hippocampus following transient forebrain ischemia SO MOLECULAR BRAIN RESEARCH LA English DT Article DE growth factor; choroid plexus; brain injury; microglia; GFAP; hybridization, in-situ ID CEREBRAL-ISCHEMIA; MESSENGER-RNA; NITRIC-OXIDE; BRAIN INJURY; TGF-BETA; GLOBAL-ISCHEMIA; GENE-EXPRESSION; NERVOUS-SYSTEM; INFARCT SIZE; CELL-GROWTH AB Although transforming growth factor-beta (TGF-beta) is known to be multifunctional in many physiological systems, its role in the brain is undergoing elucidation. The situation is made more complex by the presence of multiple isoforms, which may be differentially regulated and have various activities in each particular cell type. Because neurons are dependent on neurotrophic factors for survival, we utilized a rat model of transient forebrain ischemia (TFI) to test the hypothesis that TGF-beta isoforms are important in the hippocampal response to injury. Northern blot analysis demonstrated a differential and temporal alteration in TGF-beta isoform expression following TFI. Ln-situ hybridization experiments revealed that at day 1 following TFI. there was a strong neuronal increase in the TGF beta-1 transcript but a reciprocal decrease in TGF-beta 2 and -beta 3 transcript levels, Immunohistochemical analysis of all three TGF-beta s demonstrated at day 1 following TFI a loss of the immunoreactive proteins in the vulnerable CA-1 hippocampal neurons, but protein preservation in the CA-2-4 neurons which are more resistant to the ischemic insult. At 3-5 days following TFI, significant extraneuronal changes in TGF-beta isoform expression were also detected. Double-staining experiments with antibody to glial fibrillary acidic protein (GFAP) as a marker for astrocytes, and lectin isolectin B4 Griffonia simplicifolia for microglia, demonstrated increased expression of all TGF-beta isoforms in astrocytes but not microglia. Taken together, these results suggest thar the TGF-beta peptides in neurons and astrocytes are important endogenous mediators in the CNS response to ischemic injury. C1 MT SINAI SCH MED,DERALD H RUTTENBURG CANC CTR,NEW YORK,NY. BROWN UNIV,RHODE ISL HOSP,DEPT NEUROSURG,PROVIDENCE,RI 02903. BROWN UNIV,RHODE ISL HOSP,DEPT MED ONCOL,PROVIDENCE,RI 02903. NCI,DEPT HLTH & HUMAN SERV,NIH,BETHESDA,MD. RP Knuckey, NW (reprint author), SIR CHARLES GAIRDINER HOSP,DEPT NEUROSURG,VERDON ST,NEDLANDS,WA,AUSTRALIA. NR 69 TC 82 Z9 84 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG PY 1996 VL 40 IS 1 BP 1 EP 14 PG 14 WC Neurosciences SC Neurosciences & Neurology GA UZ118 UT WOS:A1996UZ11800001 ER PT J AU Messersmith, DJ Kim, DJ Gu, J Dubner, R Iadarola, MJ AF Messersmith, DJ Kim, DJ Gu, J Dubner, R Iadarola, MJ TI C-Jun activation of the DYNCRE3 site in the prodynorphin promoter SO MOLECULAR BRAIN RESEARCH LA English DT Article DE c-Jun; prodynorphin; PC12 cell; transient transfection; gel supershift analysis; gene regulation ID SPINAL-CORD; BINDING PROTEIN; GENE-EXPRESSION; RAT STRIATUM; PHOSPHORYLATION; INFLAMMATION; DYNORPHIN; FOS; PROENKEPHALIN; HYPERALGESIA AB The DYNCRE3 site in the prodynorphin promoter is similar to both the AP-I and cAMP-responsive element (CRE) consensus sequences. Because c-Jun is known to bind to both AP-1 and CRE sequences, we evaluated the potential role of this transcription factor at the DYNCRE3 site using transient transfection and gel mobility shift analyses. In PC12 cells, co-transfections of a chloramphenicol acetyl transferase (CAT) reporter gene containing the DYNCRE3 site and a c-Jun expression vector resulted in transcriptional activity 9-fold greater than control. Co-transfections with a mutant c-Jun protein lacking the transactivation domain resulted in a concentration-dependent decrease in transcriptional activity. Gel mobility shift analysis demonstrated the formation of a multi-component protein-DNA complex between an oligonucleotide centered on the DYNCRE3 site and nuclear extract from untreated and forskolin-stimulated PC12 cells. The upper band of this complex could be completely supershifted with the addition of a c-Jun specific antibody. These convergent data suggest that c-Jun is involved in transcriptional activation through the DYNCRE3 site. RP Messersmith, DJ (reprint author), NIDR, NEUROBIOL & ANESTHESIOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 27 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG PY 1996 VL 40 IS 1 BP 15 EP 21 PG 7 WC Neurosciences SC Neurosciences & Neurology GA UZ118 UT WOS:A1996UZ11800002 ER PT J AU Safieddine, S Bartolami, S Wenthold, RJ Eybalin, M AF Safieddine, S Bartolami, S Wenthold, RJ Eybalin, M TI Pre- and postsynaptic M3 muscarinic receptor mRNAs in the rodent peripheral auditory system SO MOLECULAR BRAIN RESEARCH LA English DT Article DE acetylcholine; efferent innervation; cochlea; superior olivary complex; guinea pig; rat; hybridization, in-situ; reverse transcriptase-polymerase chain reaction ID OUTER HAIR-CELLS; INOSITOL PHOSPHATE FORMATION; GUINEA-PIG; ACETYLCHOLINE-RECEPTOR; COCHLEAR-NUCLEUS; RAT COCHLEA; OLIVOCOCHLEAR NEURONS; CHOLINE-ACETYLTRANSFERASE; IN-VITRO; RELEASE AB The medial and lateral efferent innervations originate from distinct parts of the superior olivary complex. Both use acetylcholine, respectively, to modulate the activity of outer hair cells (OHC), and spiral ganglion neurons (SGN) which are postsynaptic to the inner hair cells (IHC). Besides predominantly activating nicotinic receptors, acetylcholine recognizes muscarinic M3 receptors, whose the role(s) and cellular localization(s) are not yet firmly established. We used reverse transcription and polymerase chain reaction to amplify the M3 receptor cDNA in the rat and guinea pig organ of Corti and spiral ganglion. Then, we localized the M3 receptor mRNAs in cochleas and superior olivary complex of both species. The M3 receptor cDNA was amplified from samples of brain, organ of Corti and spiral ganglion. Indeed, its corresponding mRNA was localized in SGNs, OHCs and IHCs. However, in the apical turns, OHCs were often found unlabeled. In the superior olivary complex, M3 mRNAs were colocalized with choline acetyltransferase mRNAs in neurons of the lateral superior olive and ventral nucleus of the trapezoid body. These results suggest that the M3 receptor-induced inositol phosphate formation described in previous studies [21] takes place in both postsynaptic (SGNs, OHCs) and presynaptic components of efferent cochlear synapses, and in cells that are not contacted by efferents in the adult cochlea (IHCs). C1 INSERM U254,F-34295 MONTPELLIER 05,FRANCE. UNIV MONTPELLIER 1,CHU HOP ST CHARLES,LAB NEUROBIOL AUDIT,F-34295 MONTPELLIER 05,FRANCE. UNIV MONTPELLIER 2,F-34095 MONTPELLIER 05,FRANCE. INSERM U432,F-34095 MONTPELLIER 05,FRANCE. NIDOCD,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. RI EYBALIN, Michel/A-9895-2011 OI EYBALIN, Michel/0000-0001-9086-1856 NR 51 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG PY 1996 VL 40 IS 1 BP 127 EP 135 PG 9 WC Neurosciences SC Neurosciences & Neurology GA UZ118 UT WOS:A1996UZ11800014 ER PT J AU Romualdi, P Donatini, A Izenwasser, S Cox, BM Ferri, S AF Romualdi, P Donatini, A Izenwasser, S Cox, BM Ferri, S TI Chronic intracerebroventricular cocaine differentially affects prodynorphin gene expression in rat hypothalamus and caudate-putamen SO MOLECULAR BRAIN RESEARCH LA English DT Article DE cocaine; chronic infusion; gene expression; prodynorphin mRNA; rat; hypothalamus; caudate-putamen ID MESSENGER-RNA; PHARMACOLOGY; STRIATUM; ABUSE AB We investigated the effects of sustained administration of cocaine on the regulation of prodynorphin gene expression in rat brain. Intracerebroventricular (i.c.v.) infusion of cocaine hydrochloride (30 mu g/day) for 7 days, by means of osmotic minipumps, elicited a significant 35% decrease of prodynorphin mRNA levels in rat hypothalamus and increase (22%) in caudate-putamen. At the same time and in the same animals, no significant changes were detected in the hippocampus or in the nucleus accumbens. These results indicate that continuously infused cocaine is able to modulate expression of the prodynorphin gene in opposite directions or has no effect on prodynorphin expression, depending on the brain region analysed. Cocaine, as well as opiates, might activate specific neuronal pathways, shared by different classes of drugs of abuse, involving, at least in part, the endogenous opioid system. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,BALTIMORE,MD 21224. UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. RP Romualdi, P (reprint author), UNIV BOLOGNA,DEPT PHARMACOL,IRNERIO 48,I-40126 BOLOGNA,ITALY. RI Izenwasser, Sari/G-9193-2012 NR 20 TC 25 Z9 25 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG PY 1996 VL 40 IS 1 BP 153 EP 156 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UZ118 UT WOS:A1996UZ11800019 ER PT J AU Terry, LA Boyd, J Alcorta, D Lyon, T Solomon, G Hannon, G Berchuck, A Beach, D Barrett, JC AF Terry, LA Boyd, J Alcorta, D Lyon, T Solomon, G Hannon, G Berchuck, A Beach, D Barrett, JC TI Mutational analysis of the p21/WAF1/CIP1/SDI1 coding region in human tumor cell lines SO MOLECULAR CARCINOGENESIS LA English DT Article DE p21; cyclin-dependent kinase inhibitor; cell-cycle regulation; polymorphism; single-strand conformational analysis ID ENDOMETRIAL CARCINOMA; DNA-REPLICATION; G(1) ARREST; P53-INDEPENDENT PATHWAY; HUMAN FIBROBLASTS; NUCLEAR ANTIGEN; HUMAN BREAST; P21; EXPRESSION; INDUCTION AB p21/WAF1/CIP1/SDI1 is an important cell-cycle mediator with tumor suppressor gene capabilities, and its inactivation could potentially lead to tumor progression. Because tumor suppressor genes are commonly inactivated by somatic and germline mutations, we analyzed a variety of human tumor cell lines for p21 mutations. We used single-strand conformational analysis and direct sequencing to identify possible mutations in the p21 coding region. Two base-alterations were observed in 41 immortalized human tumor cell lines. A previously reported polymorphism that results in a serine-to-arginine amino-acid substitution at codon 31 was found in 24% (10 of 41) of the tumor cell lines but was also found in 10% (six of 62) of normal parental DNAs tested and 7% (three of 43) of normal DNAs from patients with primary endometrial tumors. Another nucleotide substitution found at codon 80 resulted in the replacement of threonine with methionine. Codon 80 changes were found in 7% (three of 41) of the tumor cell lines (all endometrial) and in 2% (one of 62) of the normal parental DNAs. This change was not found in any of the primary endometrial tumors examined. The biological activity of these base changes was analyzed by using in vitro cyclin-dependent kinase 2-cyclin A kinase assays and calcium phosphate transfections. We observed that wild-type p21 and the p21 variants had similar growth-inhibitory abilities. Thus, our results suggest that mutation of the p21 gene is not prevalent in human tumor cell lines and is not a probable mechanism of inactivation of this gene. (C) 1996 Wiley-Liss, Inc.* C1 NIEHS,NIH,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. COLD SPRING HARBOR LAB,HOWARD HUGHES MED INST,COLD SPRING HARBOR,NY 11724. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. NR 46 TC 23 Z9 23 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 1996 VL 16 IS 4 BP 221 EP 228 DI 10.1002/(SICI)1098-2744(199608)16:4<221::AID-MC6>3.0.CO;2-I PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA VF010 UT WOS:A1996VF01000006 PM 8784465 ER PT J AU Arora, KK Cheng, ZY Catt, KJ AF Arora, KK Cheng, ZY Catt, KJ TI Dependence of agonist activation on an aromatic moiety in the DPLIY motif of the gonadotropin-releasing hormone receptor SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ANGIOTENSIN-II RECEPTOR; SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; SIGNAL-TRANSDUCTION; LIGAND-BINDING; GNRH RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; CARBOXYL-TERMINUS AB In the GnRH receptor, the NPX(2-3)Y motif that is present in the seventh transmembrane helix of most G protein-coupled receptors is unusual in containing Asp instead of Asn but retains the highly conserved Tyr residue, The importance of this aromatic residue in the DPLIY sequence of the GnRH receptor function was analyzed by replacing Tyr(322) with Ala or Phe residues, The Y(322)A mutant receptor expressed in COS-7 cells had high agonist binding affinity, but its ability to interact with G protein(s) and to activate inositol phosphate production in response to GnRH was abolished. Although functionally inactive, the Y(322)A, mutant receptor was internalized at about 50% of the rate of the wild type receptor in agonist-treated cells, When Tyr(322) was replaced with Phe to preserve its aromatic nature, the (YF)-F-322 mutant receptor displayed normal G protein activation and inositol phosphate responses to GnRH and was internalized in the same manner as the wild type receptor, These findings demonstrate that the aromatic moiety of the Tyr(322) component of the DPLIY motif in the GnRH receptor is a critical determinant of agonist-induced receptor activation and signal transduction. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, NIH, BETHESDA, MD 20892 USA. NR 47 TC 47 Z9 48 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1996 VL 10 IS 8 BP 979 EP 986 DI 10.1210/me.10.8.979 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA651 UT WOS:A1996VA65100007 PM 8843414 ER PT J AU Laue, LL Wu, SM Kudo, M Bourdony, CJ Cutler, GB Hsueh, AJW Chan, WY AF Laue, LL Wu, SM Kudo, M Bourdony, CJ Cutler, GB Hsueh, AJW Chan, WY TI Compound heterozygous mutations of the luteinizing hormone receptor gene in Leydig cell hypoplasia SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID LIMITED PRECOCIOUS PUBERTY; PREGNANCY-SPECIFIC BETA-1-GLYCOPROTEIN; LUTROPIN-CHORIOGONADOTROPIN RECEPTOR; MESSENGER-RIBONUCLEIC-ACID; ACTIVATING POINT MUTATION; MALE PSEUDOHERMAPHRODITISM; GONADOTROPIN RECEPTORS; RAT; EXPRESSION; HYPOGONADISM AB The human LH receptor (hLHR) is a member of the G protein-coupled receptors characterized by the presence of seven-transmembrane (TM) helices. Inactivating mutations of the hLHR lead to Leydig cell hypoplasia (LCH), a form of male pseudohermaphroditism resulting from the failure of fetal testicular Leydig cell differentiation. We have identified three mutations of the hLHR in a patient with LCH: deletion of exon 8 (Delta Exon 8), A872G transition resulting in Asn(291)Ser substitution in the extracellular domain, and C1847A transversion resulting in Ser(616)Tyr substitution in the seventh TM helix. Nucleotide sequencing, gene dosage, and allele-specific amplification analyses revealed that exon 8 deletion and the two missense mutations are present in different alleles of the hLHR. Constructs of mutated hLHR (hLHR-Delta Exon8, hLHR-872/1847, hLHR-1847, and hLHR-872) were used to transfect 293 cells, and the properties of the hLHR expressed were examined. Ligand-binding assays failed to detect the expression of hLHR-Delta Exon8. Transfectants expressing hLHR-872/1847 demonstrated greatly reduced ligand binding and ligand-induced cAMP accumulation in comparison to those expressing wild type hLHR. Similar reduction in cAMP accumulation was observed in transfectants expressing hLHR-1847, but not hLHR-872 alone. These findings suggest that, in addition to the 7-TM helices, the polypeptide encoded by exon 8 plays an important role in LHR expression and signal transduction. On the other hand, glycosylation of Asn(291) may not be critical for these activities. These results also establish that LCH can result from impaired signal transduction due to compound heterozygous mutations. Implications of these mutations on structure-function relationship of the hLHR and the genotype-phenotype correlation in LCH are discussed. C1 GEORGETOWN UNIV, CHILDRENS CTR, DEPT PEDIAT, WASHINGTON, DC 20007 USA. GEORGETOWN UNIV, DEPT BIOCHEM & CELL BIOL, WASHINGTON, DC 20007 USA. STANFORD UNIV, DEPT OBSTET & GYNECOL, STANFORD, CA 94305 USA. SAN JUAN CITY HOSP, DEPT PEDIAT, SAN JUAN, PR 00907 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD-01109, HD-23273, HD-31553] NR 46 TC 95 Z9 98 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1996 VL 10 IS 8 BP 987 EP 997 DI 10.1210/me.10.8.987 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VA651 UT WOS:A1996VA65100008 PM 8843415 ER PT J AU Schauer, AT Cheng, SWC Zheng, CH StPierre, L Alessi, D Hidayetoglu, DL Costantino, N Court, DL Friedman, DI AF Schauer, AT Cheng, SWC Zheng, CH StPierre, L Alessi, D Hidayetoglu, DL Costantino, N Court, DL Friedman, DI TI The alpha subunit of RNA polymerase and transcription antitermination SO MOLECULAR MICROBIOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; INTEGRATION HOST FACTOR; N-GENE PRODUCT; ESCHERICHIA-COLI; PHAGE-LAMBDA; BACTERIOPHAGE-LAMBDA; COLIPHAGE-LAMBDA; SALMONELLA-TYPHIMURIUM; NUCLEOTIDE-SEQUENCE; RECOGNITION SITE AB The N gene product of coliphage lambda, with a number of host proteins (Nus factors), regulates phage gene expression by modifying RNA polymerase to a form that overrides transcription-termination signals. Mutations in host nus genes diminish this N-mediated antitermination. Here, we report the isolation and characterization of the rpoAD305E mutation, a single amino acid change in the carboxy terminal domain (CTD) of the alpha subunit of RNA polymerase, that enhances N-mediated antitermination, A deletion of the 3' terminus of rpoA, resulting in the expression of an alpha subunit missing the CTD, also enhances N-mediated antitermination and, similar to rpoAD305E, suppresses the effect of nus mutations, Thus, the N-Nus complex may be affected through contacts with the CTD of the alpha subunit of RNA polymerase, as is a group of regulatory proteins that influences initiation of transcription. What distinguishes our findings on the N-Nus complex from those of previous studies with transcription proteins is that all of the regulators characterized in those studies bind DNA and influence transcription initiation; whereas the N-Nus complex binds RNA and affects transcription elongation, A screen of some previously identified rpoA mutations that influence transcription activators revealed only one other amino acid change, L290H, in the CTD of the a subunit, that influences antitermination. Although our results provide evidence that interactions of the a subunit of RNA polymerase must be considered in forming models of transcription antitermination, they do not provide information as to whether the interactions of a that ultimately influence antitermination occur during initiation or during elongation of transcription. C1 UNIV MICHIGAN, SCH MED, DEPT MICROBIOL & IMMUNOL, ANN ARBOR, MI 48109 USA. NCI, FREDERICK CANC RES & DEV CTR, RES PROGRAM, FREDERICK, MD 21702 USA. CORNELL UNIV, COLL VET MED, DEPT PATHOL, CANC BIOL LAB, ITHACA, NY 14853 USA. RI Friedman, David/G-3198-2015 OI Friedman, David/0000-0002-2741-4671 FU NCRR NIH HHS [M01-RR0042]; NIAID NIH HHS [AI11459-10] NR 93 TC 19 Z9 19 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 1996 VL 21 IS 4 BP 839 EP 851 DI 10.1046/j.1365-2958.1996.451409.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA VE872 UT WOS:A1996VE87200017 PM 8878045 ER PT J AU Post, RM Weiss, SRB AF Post, RM Weiss, SRB TI A speculative model of affective illness cyclicity based on patterns of drug tolerance observed in amygdala-kindled seizures SO MOLECULAR NEUROBIOLOGY LA English DT Review DE manic depressive illness; gene expression; cyclicity; recurrence; time-off effect; endogenous adaptations; contingent tolerance ID TERM LITHIUM TREATMENT; TRH MESSENGER-RNA; LOW SERUM LEVELS; BIPOLAR DISORDER; CONTINGENT TOLERANCE; TARDIVE-DYSKINESIA; RECURRENT DEPRESSION; ANTI-DEPRESSANTS; MAINTENANCE THERAPIES; NEUROTROPHIC FACTOR AB In this article, we discuss molecular mechanisms involved in the evolution of amygdala kindling and the episodic loss of response to pharmacological treatments during tolerance development. These phenomena allow us to consider how similar principles (in different neurochemical systems) could account for illness progression, cyclicity, and drug tolerance in affective disorders. We describe the phenomenon of amygdala-kindled seizures episodically breaking through effective daily pharmacotherapy with carbamazepine and valproate, suggesting that these observations could reflect the balance of pathological vs compensatory illness-induced changes in gene expression. Under certain circumstances, amygdala-kindled animals that were initially drug responsive can develop highly individualized patterns of seizure breakthroughs progressing toward a complete loss of drug efficacy. This initial drug efficacy may reflect the combination of drug-related exogenous neurochemical mechanisms and illness-induced endogenous compensatory mechanisms. However, we postulate that when seizures are inhibited, the endogenous illness-induced adaptations dissipate (the ''time-off seizure'' effect), leading to the re-emergence of seizures, a re-induction of a new, but diminished, set of endogenous compensatory mechanisms, and a temporary period of renewed drug efficacy. As this pattern repeats, an intermittent or cyclic response to the anticonvulsant treatment emerges, leading toward complete drug tolerance. We also postulate that the cyclic pattern accelerates over time because of both the failure of robust illness-induced endogenous adaptations to emerge and the progression in pathophysiological mechanisms (mediated by long-lasting changes in gene expression and their downstream consequences) as a result of repeated occurrences of seizures. In this seizure model, this pattern can be inhibited and drug responsivity can be temporarily reinstated by several manipulations, including lowering illness drive (decreasing the stimulation current), increasing drug dosage, switching to a new drug that does not show crosstolerance to the original medication, or temporarily discontinuing treatment, allowing the illness to re-emerge in an unmedicated animal. Each of these variables is discussed in relation to the potential relevance to the emergence, progression, and suppression of individual patterns of episodic cyclicity in the recurrent affective disorders. A variety of clinical studies are outlined that specifically test the hypotheses derived from this formulation. Data from animal studies suggest that illness cyclicity can develop from the relative ratio between primary pathological processes and secondary endogenous adaptations (assisted by exogenous medications). If this proposition is verified, it further suggests that illness cyclicity is inherent to the neurobiological processes of episode emergence and amelioration, and one does not need to postulate a separate defect in the biological clock. The formulation predicts that early and aggressive long-term interventions may be optimal in order to prevent illness emergence and progression and its associated accumulating neurobiological vulnerability factors. RP NIMH, BIOL PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. NR 132 TC 73 Z9 74 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 EI 1559-1182 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD AUG PY 1996 VL 13 IS 1 BP 33 EP 60 DI 10.1007/BF02740751 PG 28 WC Neurosciences SC Neurosciences & Neurology GA VJ842 UT WOS:A1996VJ84200003 PM 8892335 ER PT J AU Sunderman, FW Varghese, AH Kroftova, OS GrbacIvankovic, S Kotyza, J Datta, AK Davis, M Bal, W Kasprzak, KS AF Sunderman, FW Varghese, AH Kroftova, OS GrbacIvankovic, S Kotyza, J Datta, AK Davis, M Bal, W Kasprzak, KS TI Characterization of pNiXa, a serpin of Xenopus laevis oocytes and embryos, and its histidine-rich, Ni(II)-binding domain SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Review DE 2'-deoxyguanosine oxidation; histidyl peptide interactions; developmental regulation of proteolysis; ovochymase; DNA base damage; immunohistochemical staining; serine proteinase inhibition; teratogenesis ID GLYCYLGLYCYL-L-HISTIDINE; HUMAN-SERUM-ALBUMIN; DNA-BASE DAMAGE; HYDROGEN-PEROXIDE; FETAX PROCEDURE; NICKEL(II)-TRANSPORT SITE; AFFINITY-CHROMATOGRAPHY; NI2+-BINDING PROTEIN; ESCHERICHIA-COLI; REACTIVE CENTER AB A Ni(II)-binding serpin, pNiXa, is abundant in Xenopus oocytes and embryos. Kinetic assays show that purified pNiXa strongly inhibits bovine alpha-chymotrypsin (K-i = 3 mM), weakly inhibits porcine elastase (K-i = 0.5 mu M), and does not inhibit bovine trypsin. The reversible, slow-binding inhibition of alpha-chymotrypsin by pNiXa is unaffected by Ni(II). Ovochymase in egg exudates is inhibited by pNiXa, but to a limited extent, even at high pNiXa concentrations. An octadecapeptide that models the His-rich domain (-HRHRHEQQGHHDSAKHGH-) of pNiXa forms six-coordinate, octahedral Ni(II)-complexes when the N-terminus is acetylated, and a square-planar Ni(II)-complex when the N-terminus is unblocked. Spectroscopy reveals two distinct types of octahedral Ni(II)-coordination to the N-acetylated octadecapeptide, involving, respectively, 3-4 and 5-6 imidazole nitrogens; the octadecapeptide undergoes partial, reversible precipitation in pH- and Ni(II)-dependent fashion, suggesting an insoluble, Ni(II)-coupled (Hx)(n)-dimer. Such (Hx)(n)-peptide interaction is confirmed by an enzyme-linked biotin-avidin assay with N-biotin-KHRHRHE-amide and N-acetylKHRHRHE-resin beads, which become coupled after adding Ni(II) or Zn(II). H2O2 oxidation of 2'-deoxyguanosine to mutagenic 8-hydroxy-2'-deoxyguanosine is enhanced by the octahedral Ni(II)-octadecapeptide complex, although the effect is more intense with the square-planar Ni(II)-octadecapeptide complex. Immunoperoxidase staining of whole mounts with pNiXa antibody shows that pNiXa is distributed throughout gastrula-stage embryos and is localized during organogenesis in the brain, eye, spinal cord, myotomes, craniofacial tissues, and other sites of Ni(II)induced anomalies. Patterns of pNiXa staining are similar in controls and Ni(II)-exposed embryos. Binding of Ni(II) to pNiXa may cause embryotoxicity by enhancing oxidative reactions that produce tissue injury and genotoxicity. Although the natural target proteinases for pNiXa inhibition have not been established, pNiXa may be an important regulator of proteolysis during embryonic development. (C) 1996 Wiley-Liss, Inc. C1 NCI, COMPARAT CARCINOGENESIS LAB, FREDERICK CANC RES & DEV CTR, NIH, FREDERICK, MD USA. RP UNIV CONNECTICUT, CTR HLTH, SCH MED, DEPT LAB MED, 263 FARMINGTON AVE, FARMINGTON, CT 06030 USA. FU NIEHS NIH HHS [ES-05331-06] NR 103 TC 21 Z9 21 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1040-452X EI 1098-2795 J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD AUG PY 1996 VL 44 IS 4 BP 507 EP 524 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA VA642 UT WOS:A1996VA64200011 PM 8844694 ER PT J AU Chen, R Bolton, CF AF Chen, R Bolton, CF TI Phrenic nerve conduction studies in the intensive care unit - Reply SO MUSCLE & NERVE LA English DT Letter C1 UNIV WESTERN ONTARIO,DEPT CLIN NEUROL SCI,LONDON,ON,CANADA. RP Chen, R (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,NIH BLDG 10,ROOM 5N234,10 CTR DR,MSC 1430,BETHESDA,MD 20892, USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 2 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD AUG PY 1996 VL 19 IS 8 BP 1057 EP 1058 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UZ739 UT WOS:A1996UZ73900024 ER PT J AU Peters, R Sikorski, RS AF Peters, R Sikorski, RS TI Combinatorial libraries on the Web SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 1996 VL 14 IS 8 BP 1031 EP 1031 DI 10.1038/nbt0896-1031a PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UZ199 UT WOS:A1996UZ19900040 ER PT J AU Eisenhofer, G McCarty, R Pacak, K Russ, H Schomig, E AF Eisenhofer, G McCarty, R Pacak, K Russ, H Schomig, E TI Disprocynium24, a novel inhibitor of the extraneuronal monoamine transporter, has potent effects on the inactivation of circulating noradrenaline and adrenaline in conscious rat SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE noradrenaline kinetics; adrenaline kinetics; normetanephrine kinetics; metanephrine kinetics; extraneuronal transporter; monoamine uptake; catechol-O-methyltransferase ID CATECHOL-O-METHYLTRANSFERASE; PLASMA DIHYDROXYPHENYLGLYCOL; CELL-LINE; NOREPINEPHRINE; METABOLISM; 3,4-DIHYDROXYPHENYLGLYCOL; CLEARANCE; KINETICS; OXIDASE; UPTAKE2 AB The role of extraneuronal uptake in terminating the actions of catecholamines has been difficult to evaluate in vivo, largely because of lack of suitable inhibitors. The compound, 1,1'-diisopropyl-2,4'-cyanine iodide or disprocynium24 (D24), is a novel inhibitor of extraneuronal uptake with a high degree of potency in vitro. This study examined the actions of D24 on the inactivation and metabolism of circulating noradrenaline and adrenaline in conscious rats. Animals received i.v. infusions of H-3-labelled noradrenaline and adrenaline, and their extraneuronal O-methylated metabolites, normetanephrine and metanephrine. Plasma concentrations of endogeneous and H-3-labelled catecholamines and metanephrines were measured before and after D24. D24 caused large increases in plasma concentrations of noradrenaline and adrenaline, effects due to both decreases in their plasma clearances and increases in their rates of release into plasma, Plasma concentrations of normetanephrine and metanephrine also increased due to their decreased clearance from plasma. Increased release of normetanephrine into plasma did not contribute to increased plasma concentrations of normetanephrine. In fact, the contribution of extraneuronal O-methylation to noradrenaline clearance decreased substantially after D24. The data indicate that D24 is a potent inhibitor of the extraneuronal catecholamine transporter in vivo and that this process contributes importantly to the removal of circulating catecholamines and their O-methylated amine metabolites. Increased release of noradrenaline into plasma may reflect an increase in the proportion of transmitter that escapes from sites of release into the circulation. However, increased adrenaline release indicates that the drug also causes sympathoadrenal. activation. C1 UNIV VIRGINIA,DEPT PSYCHOL,CHARLOTTESVILLE,VA 22903. UNIV REGENSBURG,NEUROL & PSYCHIAT KLIN,D-93043 REGENSBURG,GERMANY. UNIV HEIDELBERG,INST PHARMAKOL,D-69120 HEIDELBERG,GERMANY. RP Eisenhofer, G (reprint author), NINCDS,CLIN NEUROSCI BRANCH,NIH,BLDG 10,ROOM 4D18,10 CTR DR,MSC 1424,BETHESDA,MD 20892, USA. NR 31 TC 29 Z9 29 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD AUG-SEP PY 1996 VL 354 IS 3 BP 287 EP 294 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VE677 UT WOS:A1996VE67700009 PM 8878058 ER PT J AU Gentile, NT Spatz, M Brenner, M McCarron, RM Hallenbeck, JM AF Gentile, NT Spatz, M Brenner, M McCarron, RM Hallenbeck, JM TI Decreased calcium accumulation in isolated nerve endings during hibernation in ground squirrels SO NEUROCHEMICAL RESEARCH LA English DT Article DE hibernation; calcium chloride; omega-conotoxin GVIA; omega-conotoxin MVIIC; omega-agatoxin TVA; voltage-sensitive calcium channels ID RAT-BRAIN SYNAPTOSOMES; BLOCKS SYNAPTIC TRANSMISSION; OMEGA-CONOTOXIN GVIA; ACETYLCHOLINE-RELEASE; SPERMOPHILUS-RICHARDSONII; FUNCTIONAL EXPRESSION; CEREBRAL-ISCHEMIA; CHANNEL BLOCKERS; ELECTRIC ORGAN; CA2+ CHANNELS AB Resting and depolarization-induced (CaCl2)-Ca-45, accumulation was compared for synaptosomes isolated from hibernating and nonhibernating ground squirrels. Channel subtype antagonists were used to identify the active voltage-sensitive calcium channel subtypes in these preparations. There was significantly less Ca-45(2+) accumulation in synaptosomes isolated from hibernating as compared to cold-adapted nonhibernating ground squirrels in both basal (p < 0.005) and depolarizing (p, < 0.03) media over a 30 sec to 5 min incubation period. The elevation in Ca-45(2+) accumulation triggered by K+ depolarization was blocked by 50 mu M CdCl2, 1 mu M omega-conotoxin MVIIC or 1 mu M omega-agatoxin IVA. Inhibition was not observed with 1 mu M nifedipine or with 1 mu M omega-conotoxin GVIA. These results suggest that hibernation is associated with reduced presynaptic Ca-45(2+) conductance via voltage-sensitive channels with a pharmacological sensitivity that is different from the established L-, N-, and P-types in other systems but share features of the recently described Q-type calcium channel. This decrease may reflect a cellular adaptation that helps confer tolerance to the near total cerebral ischemia associated with hibernation. RP Gentile, NT (reprint author), NINCDS,STROKE BRANCH,NIH,BLDG 36,ROOM 4A04,36 CONVENT DR,MSC 4128,BETHESDA,MD 20892, USA. NR 50 TC 21 Z9 21 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD AUG PY 1996 VL 21 IS 8 BP 947 EP 954 DI 10.1007/BF02532345 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VL523 UT WOS:A1996VL52300012 PM 8895849 ER PT J AU Makrigiannakis, A Zoumakis, E Margioris, AN Stournaras, C Chrousos, GP Gravanis, A AF Makrigiannakis, A Zoumakis, E Margioris, AN Stournaras, C Chrousos, GP Gravanis, A TI Regulation of the promoter of the human corticotropin-releasing hormone gene in transfected human endometrial cells SO NEUROENDOCRINOLOGY LA English DT Article DE corticotropin-releasing hormone; clinical neuroendocrinology; molecular neuroendocrinology ID MONOPHOSPHATE-RESPONSIVE ELEMENT; MESSENGER-RIBONUCLEIC-ACID; EPIDERMAL GROWTH-FACTOR; HUMAN-PLACENTA; ADENOCARCINOMA CELLS; GLUCOCORTICOID RECEPTOR; STRESS-RESPONSE; CYCLIC-AMP; EXPRESSION; LINE AB Corticotropin-releasing hormone (CRH) is expressed in several peripheral tissues, including normal epithelial cells of the human and rodent uterus. However, the biological role of endometrial CRH is known in neither species. As a first step to clarify this role, we studied the regulation of CRH promoter in endometrial cells. We performed homologous transfection experiments in Ishikawa cells, a human endometrial cell line, using a 0.9-kb fragment of the 5'-flanking region of the human CRH gene coupled to luciferase. Transfected cells were exposed for 18 h to 8-bromo cyclic adenosine monophosphate, forskolin, epidermal growth factor, steroids (estradiol, progesterone, and the synthetic glucocorticoid dexamethasone and their antagonists), and prostaglandin E(2); then the activity of the luciferase reporter was determined in the cell lysates. We found that the activity of the 5'-flanking region of the CRH gene was stimulated by cyclic adenosine monophosphate and epidermal growth factor and inhibited in a receptor-mediated, dose-dependent fashion by estradiol and dexamethasone. The antiglucocorticoid RU 486 acted as a glucocorticoid agonist, suppressing the CRH gene activation, while progesterone was devoid of any activity. Prostaglandin E(2) stimulated the CRH activation, and the prostanoid inhibitor indomethacin suppressed it, most probably by inhibiting endogenous prostaglandins. These findings suggest that endometrial CRH gene expression may be under the negative control of estrogens and glucocorticoids and under the positive control of prostaglandin E(2). C1 UNIV CRETE,SCH MED,DEPT PHARMACOL,GR-71110 IRAKLION,GREECE. UNIV CRETE,SCH MED,DEPT CLIN CHEM,IRAKLION,GREECE. UNIV CRETE,SCH MED,DEPT BIOCHEM,IRAKLION,GREECE. NIH,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 53 TC 52 Z9 52 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD AUG PY 1996 VL 64 IS 2 BP 85 EP 92 DI 10.1159/000127103 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA VA740 UT WOS:A1996VA74000002 PM 8857602 ER PT J AU Clark, VP Keil, K Maisog, JM Courtney, S Ungerleider, LG Haxby, JV AF Clark, VP Keil, K Maisog, JM Courtney, S Ungerleider, LG Haxby, JV TI Functional magnetic resonance imaging of human visual cortex during face matching: A comparison with positron emission tomography SO NEUROIMAGE LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; INDIVIDUAL VARIABILITY; OBJECT; ORGANIZATION; TOPOGRAPHY; LOCATIONS; MACAQUE; STRIATE; MONKEY; AREAS AB Cortical areas associated with the perception of faces mere identified using functional magnetic resonance imaging (fMRI). T2*-weighted gradient echo, echo-planar MR images were obtained using a modified 1.5-T GE Signa MRI. In all nine subjects studied, performance of a face-matching task was associated with a region of significantly increased MR signal in the ventral occipitotemporal cortex, extending from the inferior occipital sulcus to the lateral occipitotemporal sulcus and fusiform gyrus. Smaller and more variable signal increases were found in dorsolateral occipitoparietal cortex near the intraparietal sulcus. Signal decreases were found in the angular gyrus and posterior cingulate cortex. Single-subject fMRI analyses revealed discrete areas of activation with well-defined borders. Group analyses of spatially smoothed fMRI data produced results that replicated most aspects of previous studies of face processing using positron emission tomography (PET). These results show that PET and fMRI identify functional areas with similar anatomical locations. In addition, fMRI reveals interindividual variation in the anatomical location of higher-level processing areas with greater anatomical precision. (C) 1996 Acdaemic Press, Inc. RP Clark, VP (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,NIH,BETHESDA,MD 20892, USA. RI Clark, Vincent/B-3343-2010 OI Clark, Vincent/0000-0002-9151-2102 NR 43 TC 184 Z9 184 U1 1 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 1996 VL 4 IS 1 BP 1 EP 15 DI 10.1006/nimg.1996.0025 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA VF844 UT WOS:A1996VF84400001 PM 9345493 ER PT J AU Dobyns, WB Andermann, E Andermann, F CzapanskyBeilman, D Dubeau, F Dulac, O Guerrini, R Hirsch, B Ledbetter, DH Lee, NS Motte, J Pinard, JM Radtke, RA Ross, ME Tampieri, D Walsh, CA Truwit, CL AF Dobyns, WB Andermann, E Andermann, F CzapanskyBeilman, D Dubeau, F Dulac, O Guerrini, R Hirsch, B Ledbetter, DH Lee, NS Motte, J Pinard, JM Radtke, RA Ross, ME Tampieri, D Walsh, CA Truwit, CL TI X-linked malformations of neuronal migration SO NEUROLOGY LA English DT Article ID DOUBLE CORTEX SYNDROME; LOWE OCULOCEREBRORENAL SYNDROME; DIFFUSE CORTICAL DYSPLASIA; FAMILIAL BAND HETEROTOPIAS; LENNOX-GASTAUT SYNDROME; NODULAR HETEROTOPIA; GRAY-MATTER; TUBEROUS SCLEROSIS; CEREBRAL-CORTEX; SYNDROME GENE AB Malformations of neuronal migration such as lissencephaly (agyria-pachygyria spectrum) are well-known causes of mental retardation and epilepsy that are often genetic. For example, isolated lissencephaly sequence and Miller-Dieker syndrome are caused by deletions involving a lissencephaly gene in chromosome 17p13.3, while many other malformation syndromes have autosomal recessive inheritance. In this paper, we review evidence suppor ting the existence of two distinct X-linked malformations of neuronal migration. X-linked lissencephaly and subcortical band heterotopia (XLIS) presents with sporadic or familial mental retardation and epilepsy, The brain malformation varies from classical lissencephaly, which is observed in males, to subcortical band heterotopia, which is observed primarily in females, The XLIS gene is located in chromosome Xq22.3 based on the breakpoint of an X-autosomal translocation. Bilateral periventricular nodular heterotopia (BPNH) usually presents with sporadic or familial epilepsy with normal intelligence, primarily in females, although we have evaluated two boys with BPNH and severe mental retardation. The gene for BPNH has been mapped to chromosome Xq28 based on linkage studies in multiplex families and observation of a subtle structural abnormality in one of the boys with BPNH and severe mental retardation. C1 UNIV MINNESOTA, SCH MED, DEPT LAB MED & PATHOL, MINNEAPOLIS, MN 55455 USA. UNIV MINNESOTA, SCH MED, DEPT RADIOL, MINNEAPOLIS, MN 55455 USA. MCGILL UNIV, DEPT HUMAN GENET, MONTREAL, PQ H3A 2T5, CANADA. MCGILL UNIV, DEPT RADIOL, MONTREAL, PQ H3A 2T5, CANADA. HOP ST VINCENT DE PAUL, DEPT NEUROPEDIAT, F-75674 PARIS, FRANCE. STELLA MARIS FDN, DIV CHILD NEUROL & PSYCHIAT, PISA, ITALY. UNIV PISA, I-56100 PISA, ITALY. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. DUKE UNIV, DEPT NEUROL, DURHAM, NC 27706 USA. BETH ISRAEL HOSP, DEPT NEUROL, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. MCGILL UNIV, DEPT NEUROL & NEUROSURG, MONTREAL, PQ H3A 2T5, CANADA. MCGILL UNIV, MONTREAL NEUROL INST, MONTREAL, PQ H3A 2T5, CANADA. AMER MEM HOSP, UNITE NEUROPEDIAT, REIMS, FRANCE. RP Dobyns, WB (reprint author), UNIV MINNESOTA, SCH MED, DEPT NEUROL, BOX 486 UMHC, 420 DELAWARE ST SE, MINNEAPOLIS, MN 55455 USA. OI Dobyns, William/0000-0002-7681-2844 NR 65 TC 182 Z9 185 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG PY 1996 VL 47 IS 2 BP 331 EP 339 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA VC634 UT WOS:A1996VC63400003 PM 8757001 ER PT J AU Karp, BI Yang, JC Khorsand, M Wood, R Merigan, TC AF Karp, BI Yang, JC Khorsand, M Wood, R Merigan, TC TI Multiple cerebral lesions complicating therapy with interleukin-2 SO NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; BLOOD-BRAIN-BARRIER; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; TRANSIENT CORTICAL BLINDNESS; VIRUS TYPE-1 INFECTION; RENAL-CELL CARCINOMA; RECOMBINANT INTERLEUKIN-2; HYPERTENSIVE ENCEPHALOPATHY; CANCER-PATIENTS AB We reviewed the records and radiologic studies of eight patients who developed new focal neurologic abnormalities while receiving interleukin-2 (IL2)-based immunotherapy for malignancy or HIV infection. Initial confusion and delirium in the patients evolved into coma, ataxia, hemiparesis, seizures, and cortical syndromes including aphasia, apraxia, and cortical blindness. Imaging studies showed multiple white and gray matter lesions with a predilection for the occipital poles, centrum semiovale, and cerebellum. After cessation of IL2 treatment, seven patients improved to normal or near-normal neurologic function paralleled by resolution of the lesions on scans. One patient improved only minimally. Possible etiologies for the lesions include an IL-induced cerebral vasculopathy, a direct toxic effect of IL2, or immunologically mediated damage. C1 NCI, NIH, BETHESDA, MD 20892 USA. UNIV WISCONSIN, CTR COMPREHENS CANC, MADISON, WI 53706 USA. STANFORD UNIV, CTR AIDS RES, STANFORD, CA 94305 USA. RP NINCDS, NIH, BLDG 10, RM 5N-226, BETHESDA, MD 20892 USA. RI Wood, Robin/G-8509-2011 NR 53 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD AUG PY 1996 VL 47 IS 2 BP 417 EP 424 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA VC634 UT WOS:A1996VC63400017 PM 8757014 ER PT J AU Blaxton, TA AF Blaxton, TA TI Distinguishing false from true in human memory SO NEURON LA English DT Review ID POSITRON EMISSION TOMOGRAPHY; EPISODIC MEMORY; HUMAN BRAIN; RETRIEVAL; RECOGNITION; HIPPOCAMPUS RP Blaxton, TA (reprint author), NINCDS,NIH,BETHESDA,MD 20892, USA. NR 17 TC 8 Z9 8 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD AUG PY 1996 VL 17 IS 2 BP 191 EP 194 DI 10.1016/S0896-6273(00)80150-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VE840 UT WOS:A1996VE84000001 PM 8780642 ER PT J AU Bhagwat, SV Bhamre, S Boyd, MR Ravindranath, V AF Bhagwat, SV Bhamre, S Boyd, MR Ravindranath, V TI Cerebral metabolism of imipramine and a purified flavin-containing monooxygenase from human brain SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE drug metabolism; psychoactive drugs; brain; flavin-containing monooxygenase (FMO); human subjects ID MEDIATED METABOLISM; POLYACRYLAMIDE GELS; CATALYTIC ACTIVITY; HUMAN LIVER; RAT; PROTEINS; LOCALIZATION; MICROSOMES; CLONING; OXIDASE AB Flavin-containing monooxygenase (FMO), previously reported both from hepatic and extrahepatic tissues, including brain, catalyze the oxidation of certain xenobiotics and drugs that contain a nucleophilic heteroatom. Psychoactive drugs, including the antidepressant imipramine, are substrates for the brain FMO. Since FMO-mediated metabolism of these drugs might contribute to local pharmacodynamic modulation within the human brain, the metabolism of imipramine by human brain FMO was studied in further detail. In the present study, the FMO activity was determined in human brain microsomes by estimating the actual amount of imipramine N-oxide formed. It was then compared with the corresponding activity measured using substrate (imipramine)-stimulated rates of nicotinamide adenine dinucleotide phosphate (NADPH) oxidation, which teas significantly higher than the activity estimated as the amount of N-oxide assayed using high-pressure liquid chromatography (HPLC). The brain FMO activity was measurable only in the presence of detergents (sodium cholate or Lubrol PX) or in microsomes that were freeze-thawed several times. The activity was inhibited by an antibody to rabbit pulmonary FMO, but an antiserum to the mt liver NADPH cytochrome P-450 reductase had no effect indicating that cytochrome P-450 was not involved in the above metabolic pathway. The optimum pH for N-oxidation of imipramine was found to be 8.5; thermolability experiments indicated that the FMO activity was completely lost only after the incubation of brain microsomes at 45 degrees C for 20 minutes. An FMO purified to apparent homogeneity from a human brain had a molecular weight of 71,000 Da. The purified enzyme cross-reacted with the antibody to rabbit pulmonary FMO and efficiently catalyzed the metabolism of imipramine to its N-oxide. The human brain clearly contains an active FMO system, and it is conceivable that such enzymes are significantly involved in the focal metabolism and modulation of pharmacological and/or toxic effects of certain xenobiotics, including psychoactive drugs. C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,BANGALORE 560029,KARNATAKA,INDIA. NCI,LAB DRUG DISCOVERY,DEV THERAPEUT PROGRAM,NIH,FREDERICK,MD. NR 22 TC 16 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1996 VL 15 IS 2 BP 133 EP 142 DI 10.1016/0893-133X(95)00175-D PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UZ824 UT WOS:A1996UZ82400004 PM 8840349 ER PT J AU Raffaele, KC Asthana, S Berardi, A Haxby, JV Morris, PP Schapiro, MB Soncrant, TT AF Raffaele, KC Asthana, S Berardi, A Haxby, JV Morris, PP Schapiro, MB Soncrant, TT TI Differential response to the cholinergic agonist arecoline among different cognitive modalities in Alzheimer's disease SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Alzheimer's disease; arecoline; acetylcholine; memory ID MUSCARINIC RECEPTORS; CONTROLLED TRIAL; SENILE DEMENTIA; BASAL FOREBRAIN; MEMORY; RAT; PHYSOSTIGMINE; ASYMMETRIES; MECHANISMS; METABOLISM AB Nine patients with possible or probable dementia of the Alzheimer type were tested on nine cognitive tests prior to (two times) and during continuous intravenous administration of five different doses of the muscarinic cholinergic agonist arecoline (1, 4, 16, 28, and 40 mg/day). The present analysis examined whether improvement on cognitive testing for each patient during arecoline treatment was most likely to occur at the same dose for all tests or whether different test scores improved at different doses of arecoline. Results indicated there were significant differences among tests in the dose at which most patients showed improved cognitive performance. These differences may have therapeutic significance, as verbal ability tended to improve at low doses of arecoline, whereas attention and visuospatial ability tended to improve at higher doses of arecoline. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 51 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1996 VL 15 IS 2 BP 163 EP 170 DI 10.1016/0893-133X(95)00179-H PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UZ824 UT WOS:A1996UZ82400007 PM 8840352 ER PT J AU Stein, MB Chen, G Potter, WZ Manji, HK AF Stein, MB Chen, G Potter, WZ Manji, HK TI G-protein level quantification in platelets and leukocytes from patients with panic disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE G protein; panic disorder; adrenergic receptors; social phobia ID SIGNAL-TRANSDUCTION PATHWAYS; BETA-ADRENERGIC RECEPTORS; ADENYLATE-CYCLASE; BINDING PROTEINS; GENE-EXPRESSION; CEREBRAL-CORTEX; DESENSITIZATION; ANTIDEPRESSANTS; MEMBRANES; ANXIETY AB The objective of our study was to investigate if there ave abnormalities in signal transducing G proteins in patients with panic disorder We utilized selective antibodies to quantitate the levels of the G protein a subunits that regulate adenylyl cyclase activity (G alpha(s) and G alpha(i2)) and phosphoinositide turnover (G alpha(q/11)) in platelet membranes (and leukocyte membranes for G(alpha s)), and also carried out pertussis toxin (PT) catalyzed [P-32]ADP-ribosylation in platelet membranes from a group of 13 untreated panic disorder patients, 10 untreated social phobia patients, and 12 healthy subjects. There were no significant differences among the three groups in the immunolabeling of G alpha(a) in platelets or leukocytes, or in the immunolabeling of G alpha(i1/2), G(alpha/11), or PT-catalyzed [P-32]ADP-ribosylation in platelets. Within the constraints imposed by using peripheral blood cells to reflect brain composition, our results do not provide support for G protein abnormalities in patients with panic disorder. These results contrast with those obtained rising identical methodology in bipolar affective disorder, where elevated G(alpha s) in leukocytes has been reported (Manji et al. 1995). C1 NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,BETHESDA,MD 20892. WAYNE STATE UNIV,SCH MED,DEPT PSYCHIAT,MOLEC PATHOPHYSIOL PROGRAM,DETROIT,MI. WAYNE STATE UNIV,SCH MED,DEPT PHARMACOL,MOLEC PATHOPHYSIOL PROGRAM,DETROIT,MI. RP Stein, MB (reprint author), UNIV CALIF SAN DIEGO,DEPT PSYCHIAT 0603,ANXIETY & TRAUMAT STRESS DISORDERS RES PROGRAM,LA JOLLA,CA 92093, USA. RI Chen, Guang/A-2570-2017 NR 44 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 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1996 VL 15 IS 2 BP 180 EP 186 DI 10.1016/0893-133X(95)00182-D PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UZ824 UT WOS:A1996UZ82400009 PM 8840354 ER PT J AU Michelson, D Altemus, M Galliven, E Hill, L Greenberg, BD Gold, P AF Michelson, D Altemus, M Galliven, E Hill, L Greenberg, BD Gold, P TI Naloxone-induced pituitary-adrenal activation does not differ in patients with depression, obsessive compulsive disorder, and healthy controls SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cortisol; ACTH; naloxone; depression; obsessive-compulsive disorder; pathophysiology ID CORTICOTROPIN-RELEASING HORMONE; SECRETION INVITRO; CORTISOL-LEVELS; AXIS FUNCTION; ACTH; ANTAGONISTS; AGONISTS AB Adrenocorticotropic hormone (ACTH) and cortisol secretion have been shown to be abnormal in approximately half of depressed patients. Information from pituitary and adrenal studies suggests that the focus of this dysregulation is at or above the level of the hypothalamus; however; direct evidence from provocative studies of the hypothalamic corticotropin releasing hormone (CRH) neuron does Mot exist. The current study teas designed to stimulate hypothalamic CRH release using the opiate antagonist naloxone in patients with depression and elevated urinary-free cortisols as well as healthy and psychiatric controls. All subjects received naloxone and placebo on separate days in a double-blinded, randomized fashion at a dose determined previously to reliably induce significant increases in ACTH and cortisol secretion. No significant differences were noted among groups. We conclude that although naloxone is an effective central stimulant of the hypothalamic CRH neuron, stimulation of the hypothalamic CRH neuron with naloxone does not provide evidence of dysregulation of the HPA axis in depression. C1 NIMH, CLIN SCI LAB, BETHESDA, MD 20892 USA. RP Michelson, D (reprint author), NIMH, CLIN NEUROENDOCRINOL BRANCH, 10-3S231 MSC 1284, 10 CTR DR, BETHESDA, MD 20892 USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1996 VL 15 IS 2 BP 207 EP 212 DI 10.1016/0893-133X(95)00210-5 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UZ824 UT WOS:A1996UZ82400012 PM 8840357 ER PT J AU Bing, G McMillian, M Kim, H Pennypacker, K Feng, Z Qi, Q Kong, LY Iadarola, M Hong, JS AF Bing, G McMillian, M Kim, H Pennypacker, K Feng, Z Qi, Q Kong, LY Iadarola, M Hong, JS TI Long-term expression of the 35,000 mol wt fos-related antigen in rat brain after kainic acid treatment SO NEUROSCIENCE LA English DT Article DE c-fos; fos-related antigens; kainic acid activator protein-1; seizure; hippocampus ID PROGRAMMED CELL-DEATH; EARLY GENE-EXPRESSION; GROWTH-FACTOR GENE; AP-1 DNA-BINDING; C-FOS; TRANSCRIPTION; PROTEINS; SEIZURE; PROENKEPHALIN; PROMOTER AB Systemic injection of kainic acid, a rigid analogue of glutamate, induces both the short-term and the long-term expression of activator protein-1 transcription factors. The short-term responses of activator protein-1 factors such as c-fos and fos-related antigens have been well studied. However, the long-term expression of activator protein-1 factor(s) induced by kainic acid is poorly understood. The present study was designed to document the long-term expression (up to seven months) of the fos-related antigens and to map their distributions in the rat brain after systemic treatment with kainic acid. A single dose of kainic acid (8 mg/kg) was injected i.p. into Fischer 344 rats and their epileptic seizure behaviour was monitored. The rats with full limbic seizures were chosen for long-term study. By using immunocytochemistry with an antibody that cross-reacts with all known fos-related antigens, western blot analysis and a gel mobility-shift assay, we have now shown that a 35,000 mel. wt fos-related antigen was induced by kainic acid treatment and expressed at high levels for up to five months. This fos-related antigen still maintains the activator protein-1 DNA binding activity in the rat brain seven months after kainic acid treatment. The fos-related antigens and activator protein-1 binding activity were continuously expressed at high levels throughout the experimental period in the dentate granule cells where messy fibre collateral sprouting occurred after kainic acid treatment. Our results suggested that long-term expression of fos-related antigen may reflect the pathophysiological changes after kainic acid administration. Published by Elsevier Science Ltd. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. RP Bing, G (reprint author), NIEHS,LAB ENVIRONM NEUROSCI,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI bing, guoying/F-7084-2012; Pennypacker, Keith/I-5092-2012; OI Bing, Guoying/0000-0003-0609-8152 NR 46 TC 37 Z9 37 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD AUG PY 1996 VL 73 IS 4 BP 1159 EP 1174 DI 10.1016/0306-4522(96)00053-X PG 16 WC Neurosciences SC Neurosciences & Neurology GA UV988 UT WOS:A1996UV98800025 PM 8809832 ER PT J AU Travis, LB Curtis, RE Boice, JD AF Travis, LB Curtis, RE Boice, JD TI Late effects of treatment for childhood Hodgkin's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Travis, LB (reprint author), NATL CANC INST,BETHESDA,MD 20892, USA. NR 3 TC 37 Z9 37 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 1 PY 1996 VL 335 IS 5 BP 352 EP 353 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UY982 UT WOS:A1996UY98200022 PM 8668223 ER PT J AU Lang, L Aloj, L Kiesewetter, DO Jagoda, E Lee, JT Paik, CH Carrasquillo, JA Eckelman, WC AF Lang, L Aloj, L Kiesewetter, DO Jagoda, E Lee, JT Paik, CH Carrasquillo, JA Eckelman, WC TI A review of new oncotropic tracers for PET imaging SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Conference on New Trends in Nuclear Oncology CY SEP 27-29, 1995 CL NAPLES, ITALY DE F-18 radiolabeling; transferrin; muscarinics; antibody fragments ID TRANSFERRIN RECEPTORS; BREAST-CANCER; CARCINOMA; TUMORS; CELLS; BINDING AB We have developed three biochemical probes to determine if they are sensitive probes of early biochemical change in a tumor. All three probes appear to have the appropriate properties for in vivo imaging, but must now be evaluated as probes for the sensitive detection of changes in early malignant disease. RP Lang, L (reprint author), NIH,CTR CLIN,BLDG 10,RM 1C401,10 CTR DR,MSC 1180,BETHESDA,MD 20892, USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 34 TC 3 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD AUG PY 1996 VL 23 IS 6 BP 669 EP 672 DI 10.1016/0969-8051(96)00064-9 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VH671 UT WOS:A1996VH67100004 PM 8940707 ER PT J AU McAfee, JG Neumann, RD AF McAfee, JG Neumann, RD TI Radiolabeled peptides and other ligands for receptors overexpressed in tumor cells for imaging neoplasms SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Conference on New Trends in Nuclear Oncology CY SEP 27-29, 1995 CL NAPLES, ITALY DE radiolabeled peptides; radiolabeled ligands; tumor cell receptors ID MALIGNANT-MELANOMA; HORMONE; INTERLEUKIN-2; BREAST; CANCER AB For better detection of neoplasms by scintigraphy, ligands that bind specifically to surface receptors overexpressed in tumor cells are being developed. These ligands must be labeled with the readily available radionuclides of iodine, [In-111] or [Tc-99m], without blocking their interaction with the specific cell membrane receptors. The promising ligands include bioactive endogenous peptides or their analogues, inhibitors of glucose transport proteins, estrogen and sigma receptor ligands, growth factors, and cytokines. RP McAfee, JG (reprint author), NIH,DEPT NUCL MED,BLDG 10,ROOM 1C497,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 51 Z9 54 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD AUG PY 1996 VL 23 IS 6 BP 673 EP 676 DI 10.1016/0969-8051(96)00068-6 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VH671 UT WOS:A1996VH67100005 PM 8940708 ER PT J AU John, CS Gulden, ME Vilner, BJ Bowen, WD AF John, CS Gulden, ME Vilner, BJ Bowen, WD TI Synthesis, in vitro validation and in vivo pharmacokinetics of [I-125]N-[2-(4-iodophenyl)ethyl]-N-methyl-2-(1-piperidinyl)ethylamine: A high-affinity ligand for imaging sigma receptor positive tumors SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE IPEMP; sigma receptor radioligand; tumor imaging ID MALIGNANT-MELANOMA; BINDING-SITES; CELL-LINES; IDENTIFICATION; SCINTIGRAPHY; CARCINOMA; CULTURE; AGENTS; BRAIN; DRUGS AB N-[2-(4-iodophenyl)ethyl]-N-methyl-2-(1-piperidinyl)ethylamine, IPEMP, and the corresponding bromo derivative, BrPEMP, have been synthesized and characterized. Both BrPEMP and IPEMP were evaluated for sigma-1 and sigma-2 subtype receptor affinities and found to possess very high affinities for both receptor subtypes. The precursor for radioiodination n-tributylstannylphenylethylpiperidinylethylamine was prepared from its bromo derivative by palladium-catalyzed stannylation reaction. Radioiodinated 4-[I-125]PEMP was readily prepared in high yields and high specific activity by oxidative iododestannylation reaction using chloramine-T as oxidizing agent. Sites labeled by 4-[I-125]PEMP in guinea pig brain membranes showed high affinity for BD1008, haloperidol, and (+)-pentazocine (Ki = 5.06 +/- 0.40, 32.6 +/- 2.75, and 48.1 +/- 8.60 nM, respectively), which is consistent with sigma receptor pharmacology. Competition binding studies of 4-[I-125]PEMP in melanoma (A375) and MCF-7 breast cancer cells showed a high affinity, dose-dependent inhibition of binding with known sigma ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl) ethylamine, BD1008 (Ki = 5, 11 nM, respectively), supporting the labeling of sigma sites in these cells. Haloperidol, however showed a weaker (Ki = 100-200 nM) affinity for the sites labeled by 4-[I-125]PEMP in these cells. Biodistribution studies of 4-[I-125]PEMP in rats showed a fast clearance of this radiopharmaceutical from blood, liver, lung, and other organs. A co-injection of 4-IPEMP with 4-[I-125]PEMP resulted in 37%, 69%, and 35% decrease in activity in liver, kidney, and brain (organs possessing sigma receptors), respectively at 1-h postinjection. These results suggest that 4-[I-125]PEMP is a promising radiopharmaceutical for pursuing further studies in animal models with tumors. C1 NIDDK,UNIT RECEPTOR BIOCHEM & PHARMACOL,MED CHEM LAB,NIH,BETHESDA,MD. RP John, CS (reprint author), GEORGE WASHINGTON UNIV,MED CTR,RADIOPHARMACEUT CHEM SECT,661 ROSS HALL,2300 I ST NW,WASHINGTON,DC 20037, USA. FU NCI NIH HHS [CA58496] NR 34 TC 27 Z9 31 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD AUG PY 1996 VL 23 IS 6 BP 761 EP 766 DI 10.1016/0969-8051(96)00070-4 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VH671 UT WOS:A1996VH67100015 PM 8940718 ER PT J AU Crespo, P Bustelo, XR Aaronson, DS Coso, OA LopezBarahona, M Barbacid, M Gutkind, JS AF Crespo, P Bustelo, XR Aaronson, DS Coso, OA LopezBarahona, M Barbacid, M Gutkind, JS TI Rac-1 dependent stimulation of the JNK/SAPK signaling pathway by Vav SO ONCOGENE LA English DT Article DE Vav; signal transduction; JNK; MAP kinases; GTP-binding proteins ID GUANINE-NUCLEOTIDE EXCHANGE; DBL-ONCOGENE PRODUCT; RECEPTOR TYROSINE KINASE; GTP-BINDING PROTEINS; PROTOONCOGENE PRODUCT; HEMATOPOIETIC-CELLS; MOLECULAR-CLONING; RAS; ACTIVATION; PHOSPHORYLATION AB The protein product of the human vav oncogene, Vav, exhibits a number of structural motifs suggestive of a role in signal transduction pathways, including a leucine-rich region, a plekstrin homology (PH) domain, a cysteine-rich domain, two SH3 regions, an SH2 domain, and a central Dbl homology (DH) domain. However, the transforming pathway(s) activated by Vav has not yet been elucidated. Interestingly, DH domains are frequently found in guanine nucleotide-exchange factors for small GTP-binding proteins of the Ras and Rho families, and it has been recently shown that, whereas Ras controls the activation of mitogen activated kinases (MAPKs), two members of the Rho family of small GTPases, Rac 1 and Cdc42, regulate activity of stress activated protein kinases (SAPKs), also termed c-jun N-terminal kinases (JNKs). The structural similarity between Vav and other guanine nucleotide exchange factors for small GTP-binding proteins, together with the recent identification of biochemical routes specific for members of the Ras and Rho family of GTPases, prompted us to explore whether MAPK or JNK are downstream components of the Vav signaling pathways. Using the COS-7 cell transient expression system, we have found that neither Vav nor the product of the I,av proto-oncogene, proto-Vav, can enhance the enzymatic activity of a coexpressed, epitope tagged MAPK. On the other hand, we have observed that, whereas proto-Vav can slightly elevate JNK/SAPK activity, oncogenic Vav potently activates JNK/SAPK to an extent comparable to that elicited by two guanine-nucleotide exchange factors for Rho family members, Dbl and Ost. We also show that point mutations in conserved residues within the cysteine rich and DH domains of Vav both prevent its ability to activate JNK/SAPK and render Vav oncogenically inactive. In addition, we found that coexpression of the Rac-1 N17 dominant inhibitory mutant dramatically diminishes JNK/SAPK stimulation by Vav, as well as reduces the focus-forming ability of Vav in NIH3T3 murine fibroblasts. Taken together, these findings provide the first evidence that Rac-1 and JNK are integral components of the Vav signaling pathway. C1 NIDR,MOL SIGNALING UNIT,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOL BIOL,PRINCETON,NJ 08543. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 41 TC 150 Z9 151 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 1 PY 1996 VL 13 IS 3 BP 455 EP 460 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VB328 UT WOS:A1996VB32800002 PM 8760286 ER PT J AU Jackers, P Minoletti, F Belotti, D Clausse, N Sozzi, G Sobel, ME Castronovo, V AF Jackers, P Minoletti, F Belotti, D Clausse, N Sozzi, G Sobel, ME Castronovo, V TI Isolation from a multigene family of the active human gene of the metastasis-associated multifunctional protein 37LRP/p40 at chromosome 3p21.3 SO ONCOGENE LA English DT Article DE 37 kD laminin receptor precursor; 3p21.3; Alu sequences; p40 ribosome-associated protein; small nuclear RNA E2 gene ID AFFINITY LAMININ RECEPTOR; SMALL NUCLEOLAR RNAS; CELL LUNG-CANCER; RIBOSOMAL-PROTEIN; MESSENGER-RNA; TRANSLATIONAL CONTROL; BINDING-PROTEIN; MAMMALIAN-CELLS; CARCINOMA-CELLS; ALU RNA AB The 37 kD precursor of the 67 kD laminin receptor (37LRP) is a polypeptide whose expression is consistently upregulated in aggressive carcinoma. Interestingly, the 37LRP appears to be a multifunctional protein involved in the translational machinery and has also been identified as p40 ribosome-associated protein. Although highly conserved cDNAs corresponding to this polypeptide have been isolated from several species including vertebrates, invertebrates, plants and prokaryotes, characterization of any of the corresponding active genes has never been reported. In this study, we have cloned an intron-containing fragment which permitted us to isolate the active 37LRP/p40 human gene. This gene contains seven exons and six introns. Ribonuclease protection experiments suggest multiple transcription start sites. The promoter area does not bear a TATA box but contains four Sp1 sites. The first intron is also GC rich containing five Sp1 sites. Intron 4 contains the full sequence of the small nuclear RNA E2 and two Alu sequences are found in intron 3. Fluorescent in situ hybridization localized the 37LRP/p40 active gene on chromosome 3 in the locus 3p21.3 which, interestingly, is a hot spot for genetic alterations in several cancers and particularly in small cell lung carcinoma. C1 IST TUMORI,MILAN,ITALY. NCI,MOL PATHOL SECT,NIH,BETHESDA,MD 20892. RI sozzi, gabriella/G-8259-2011 OI sozzi, gabriella/0000-0001-9360-6914 NR 60 TC 48 Z9 51 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 1 PY 1996 VL 13 IS 3 BP 495 EP 503 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VB328 UT WOS:A1996VB32800007 PM 8760291 ER PT J AU Carbone, M Rizzo, P Procopio, A Giuliano, M Pass, HI Gebhardt, MC Mangham, C Hansen, M Malkin, DF Bushart, G Pompetti, F Picci, P Levine, AS Bergsagel, JD Garcea, RL AF Carbone, M Rizzo, P Procopio, A Giuliano, M Pass, HI Gebhardt, MC Mangham, C Hansen, M Malkin, DF Bushart, G Pompetti, F Picci, P Levine, AS Bergsagel, JD Garcea, RL TI SV40-like sequences in human bone tumors SO ONCOGENE LA English DT Article DE SV40; human bone tumors ID HUMAN-BRAIN-TUMORS; T-DELETION MUTANTS; SIMIAN-VIRUS 40; GROWTH-FACTOR-I; SV40; ANTIGEN; SIMIAN-VIRUS-40; MICE; GENE; TRANSFORMATION AB Simian virus 40 (SV40) is a monkey virus that induces ependymomas, choroid plexus tumors, mesotheliomas, osteosarcomas, sarcomas and true histiocytic lymphomas when injected in hamsters. Recently, approximately 60% of human ependymomas, choroid plexus tumors and mesotheliomas were reported to contain and express SV40-like sequences (N. Engl. J. Med., 1992, 36, 988-993; Oncogene, 1994, 9, 1781-1790). In this study the presence of SV40-like sequences was investigated in additional types of human tumors. Initially, 200 tumor and normal tissue DNA samples were analysed by polymerase chain reaction (PCR) with primers that were analysed by with primers that amplify a 574 base pair region of SV40 large T antigen (Tag), which includes the Rb-pocket binding domain and the intron of Tag. PCR amplification and Southern blot hybridization with a probe specific for SV40 Tag revealed that 18/200 samples contained SV40-like sequences and, unexpectedly, 11/18 were from patients with osteosarcomas. Additional DNA samples from bone tumors were then analysed. In 40/126 osteosarcomas, and 14/34 other bone-related tumors, Tag sequences could be amplified. Sequence analysis of the DNA amplified from seven different tumors confirmed that the amplified sequences corresponded to SV40 Tag, with some demonstrating deletions in the intron region but not in the Rb-pocket binding domain. The extent of SV40 genome sequences present in the DNA samples was further analysed in two osteosarcomas. PCR amplification, Southern blot hybridization, and sequence analysis revealed that these samples also contained sequences for the carboxy-terminal domain of Tag, the viral regulatory region, and the VP1 capsid protein. These results indicate that SV40-like sequences are present in human bone tumors. C1 NIH,SECT DNA REPLICAT REPAIR & MUTAGENESIS,BETHESDA,MD 20892. UNIV G DANNUNZIO,EXPT CTR GENE THERAPY & DIAG,CHIETI,ITALY. NCI,THORAC ONCOL SECT,BETHESDA,MD 20892. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. BOSTON UNIV,BOSTON,MA 02215. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. UNIV ULM,D-7900 ULM,GERMANY. IST ORTOPED RIZZOLI,BOLOGNA,ITALY. SCOTTISH RITE HOSP,ATLANTA,GA. CHILDRENS HOSP,DENVER,CO 80218. RP Carbone, M (reprint author), UNIV CHICAGO,DEPT PATHOL,5841 S MARYLAND AVE,MC3083,ROOM S-342,CHICAGO,IL 60637, USA. RI Picci, Piero/J-5979-2016 OI Picci, Piero/0000-0002-8519-4101 NR 60 TC 172 Z9 176 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 1 PY 1996 VL 13 IS 3 BP 527 EP 535 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VB328 UT WOS:A1996VB32800010 PM 8760294 ER PT J AU Braverman, RH Cooper, HL Lee, HS Prasad, GL AF Braverman, RH Cooper, HL Lee, HS Prasad, GL TI Anti-oncogenic effects of tropomyosin: Isoform specificity and importance of protein coding sequences SO ONCOGENE LA English DT Article DE tropomyosin; isoforms; tumor suppressor ID STIMULATES TYROSINE PHOSPHORYLATION; CHICKEN-EMBRYO FIBROBLASTS; MAMMARY EPITHELIAL-CELLS; NON-MUSCLE TROPOMYOSINS; CARDIAC TROPONIN-T; TRANSFORMED-CELLS; ALPHA-TROPOMYOSIN; BETA-TROPOMYOSIN; GROWTH-FACTOR; HYPERTROPHIC CARDIOMYOPATHY AB Suppression of muscle type isoforms of tropomyosin (TM) is a common biochemical event in malignantly transformed cells. To evaluate the role of TM proteins and isoform specificity in cellular transformation, cDNAs that consist of coding sequences of TM1 (product of beta gene) and TM2 (product of alpha gene), but lacking untranslated regions (UTRs), have been expressed separately in DT (v-Ki-ras transformed NIH3T3) cells, and elevated levels of the corresponding proteins were detected. DT cells which over express TM2 manifest growth in soft agar. Elevated levels of TM1 protein in DT cells resulted in flattened cell morphology and complete abolition of anchorage independent growth. Tumorigenesis in athymic nude mice was observed in the absence of transduced TM1 mRNA. Thus, expression of TM1 protein is sufficient for tumor suppression: the UTRs of TM1 are not required for the tumor suppressive effects. Expression of TM2 protein, on the other hand, has no effect on the transformed phenotype of DT cells. These data indicate that isoforms 1 and 2 of TMs perform distinct physiological roles. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 66 TC 47 Z9 49 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 1 PY 1996 VL 13 IS 3 BP 537 EP 545 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VB328 UT WOS:A1996VB32800011 PM 8760295 ER PT J AU Saxena, A Robertson, JT Ali, IU AF Saxena, A Robertson, JT Ali, IU TI Abnormalities of p16, p15 and CDK4 genes in recurrent malignant astrocytomas SO ONCOGENE LA English DT Article DE malignant astrocytomas; recurrent tumors; p16; p15; CDK4 ID EPIDERMAL GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; DEPENDENT KINASES; FACTOR RECEPTOR; HUMAN CANCERS; GLIAL TUMORS; CYCLIN-D; AMPLIFICATION; EXPRESSION; INHIBITORS AB Abnormalities in the p16, p15 and CDK4 genes that regulate transition through the G1 phase of the cell cycle have been implicated in the malignant progression of astrocytomas. The results of the present study demonstrate that dysfunction of these genes also occurs during recurrence of glial tumors that were highly malignant at first presentation. Analysis of 10 matched pairs of high grade malignant astrocytomas and their subsequent recurrences identified three distinct groups. The primary and recurrent tumors in Group A did not show structural alterations in the p16, p15 or CDK4 genes, whereas homozygous codeletion of p16 and p15 was observed in both primary and recurrent tumors in Group B. The primary tumors in Group C had a normal profile of p16, p15 and CDK4 at presentation. Upon recurrence, however, the tumors sustained either deletion of p16 alone or codeletion of both p16 and p15 or amplification of CDK4. Analysis of the molecular differences between primary anaplastic astrocytomas/glioblastomas and their subsequent recurrences, which are clinically indistinguishable, may provide better therapeutic options for treatment. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIV TENNESSEE,NINDS,NIH,SURG NEUROL BRANCH,MEMPHIS,TN 38119. UNIV TENNESSEE,DEPT NEUROSURG,MEMPHIS,TN 38119. NR 32 TC 21 Z9 21 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 1 PY 1996 VL 13 IS 3 BP 661 EP 664 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VB328 UT WOS:A1996VB32800025 PM 8760309 ER PT J AU Beem, JE Hurley, CG Nesbitt, WE Croft, DF Marks, RG Cisar, JO Clark, WB AF Beem, JE Hurley, CG Nesbitt, WE Croft, DF Marks, RG Cisar, JO Clark, WB TI Fimbrial-mediated colonization of murine teeth by Actinomyces naeslundii SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Actinomyces; fimbria; implantation; teeth ID SALIVA-TREATED HYDROXYAPATITE; HUMAN EXPERIMENTAL GINGIVITIS; VISCOSUS T14V; TYPE-1 FIMBRIAE; APATITIC SURFACES; BACTERIOLOGY; ADSORPTION; COAGGREGATION; ANTIBODIES; ADHERENCE AB Groups of mice fed diets high in sucrose or glucose were orally inoculated with 10(10), 10(9) or 10(8) colony-forming units of one of the following Actinomyces naeslundii strains possessing the type 1 (T1(+))) and/or the type 2 (T2+) fimbriae: T14V-J1 (T1+, T2+), 5519 (T1+), 5951 (T2+), and 147 (non-fimbriated). Ninety-six hours after inoculation their upper jaws were cultured to look at the implantation of each of these strains on the teeth. In mice fed a sucrose diet, regardless of the presence or absence of fimbriae, each bacterial strain colonized 100% of the mice at the highest inoculation doses of the infecting organism. But at a dose of 10(8), T14V-J1 was the only strain which colonized 100% (12/12) of the mice, 5519 colonized 10/11, 5951 colonized 9/11 and 147 colonized 7/11. These differences were not statistically significant. When mice were fed a high-glucose diet, 100% infection was achieved with strains T14V-J1, 5519 and 5951 only at the highest dose of 10(10) colony-forming units. Strain 147 colonized in 8/9 of the mice at that dosage. At lower dosages, no bacterial strain implanted in 100% of the mice. In the glucose experiment at a dose of 10(8), strains expressing the T1 fimbriae implanted significantly better than strains without the T1 fimbriae. At a dose of 10(9) colony-forming units, the parent strain T14V-J1 implanted significantly better than strains without the T1 fimbriae. Similarly, strain: 5519 (T1+) implanted significantly better than 5951 and implanted better than 147, although the difference was not significant. These results suggest that while the presence of the T1 and T2 fimbriae may confer some advantage in the establishment of these organisms in vivo, even the strains without fimbriae were able tb colonize. Strains T14VJ1 and 5519 were found to bind well to hydroxyapatite treated with mouse saliva, while strains 5951 and 147 did not. Only T2 fimbriated strains T14-V-J1 and 5951 exhibited a lactose-reversible coaggreation with indigenous strains of enterococci that may contribute to the elevated levels of colonization of strain 5951 in vivo. C1 UNIV FLORIDA,COLL DENT,PERIODONTAL DIS RES CTR,DEPT ORAL BIOL,GAINESVILLE,FL 32610. UNIV FLORIDA,DEPT STAT,GAINESVILLE,FL 32610. NIDR,MICROBIAL ECOL LAB,NIH,BETHESDA,MD 20892. NR 37 TC 2 Z9 2 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD AUG PY 1996 VL 11 IS 4 BP 259 EP 265 DI 10.1111/j.1399-302X.1996.tb00179.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA UX609 UT WOS:A1996UX60900008 PM 9002879 ER PT J AU Karron, RA Makhene, M Gay, K Wilson, MH Clements, ML Murphy, BR AF Karron, RA Makhene, M Gay, K Wilson, MH Clements, ML Murphy, BR TI Evaluation of a live attenuated bovine parainfluenza type 3 vaccine in two- to six-month-old infants SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE parainfluenza vaccine; attenuated parainfluenza virus vaccine; respiratory virus vaccine; pediatric immunization; infant immunization; attenuated vaccine ID RESPIRATORY SYNCYTIAL VIRUS; CHILDREN; EPIDEMIOLOGY; INFECTION; OUTBREAK; AGE AB Background. A safe and effective parainfluenza type 3 (PIV-3) virus vaccine is needed to prevent serious PIV-3-associated illness in infants younger than 6 months of age. In previous studies a live bovine PIV-3 (BPIV-3) vaccine, which was developed to prevent human PIV-3 (HPIV-3) disease, was shown to be safe, infectious, immunogenic and phenotypically stable in 6- to 36-month-old infants and children. Methods. The safety, infectivity and immunogenicity of a single dose of the BPIV-3 vaccine was evaluated in a randomized, placebo-controlled, double blinded trial in 19 infants 2 to 5.9 months of age and in 11 additional 6- to 36-month-old subjects. Results. The BPIV-3 vaccine was well-tolerated in both age groups and infected 92% of those younger than 6 months and 89% of those older than 6 months of age. Serum hemagglutination-inhibition (HAI) antibody responses to HPIV-3 and to BPIV-3, respectively, were detected in 42 and 67% of the younger infants, compared with 70 and 85% of the older subjects, In the younger infants we analyzed the rate of antibody response by titer of maternally acquired antibodies; low titer was defined as a preimmunization serum HAI titer <1:8 and high titer was defined as a preimmunization serum HAI titer greater than or equal to 1:8. Young infants with a low titer of maternally acquired antibodies were significantly more likely to respond to the BPIV-3 vaccine than those with a high titer (89% vs. none for serum HAI response to BPIV-3; P = 0.02, Fisher's exact test). Conclusions. This study demonstrated that the BPIV-3 vaccine was safe and infectious in infants younger than 6 months of age and was also immunogenic in the majority of these young infants, Additional studies are needed to determine whether two or more doses will enhance the immunogenicity of the BPIV-3 vaccine in young infants and to assess its safety and immunogenicity when given simultaneously with routine childhood immunizations. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIAID,INFECT DIS LAB,NATL INST HLTH,BETHESDA,MD 20892. RP Karron, RA (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,CTR IMMUNIZAT RES,HAMPTON HOUSE 125,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [N01-AI-15095] NR 17 TC 72 Z9 72 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD AUG PY 1996 VL 15 IS 8 BP 650 EP 654 DI 10.1097/00006454-199608000-00003 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA VC392 UT WOS:A1996VC39200002 PM 8858666 ER PT J AU Desposito, F Cho, S Frias, JL Sherman, J Wappner, RS Wilson, MG AF Desposito, F Cho, S Frias, JL Sherman, J Wappner, RS Wilson, MG TI Health supervision for children with fragile X syndrome SO PEDIATRICS LA English DT Article ID UNSTABLE DNA; PHENOTYPE; DIAGNOSIS; GENOTYPE C1 NIH,BETHESDA,MD 20892. HLTH RESOURCES & SERV ADM,ROCKVILLE,MD. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC 20024. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. AMER ACAD PEDIAT,SECT GENET & BIRTH DEFECTS,ELK GROVE VILLAGE,IL. AMER ACAD PEDIAT,COMM GENET,ELK GROVE VILLAGE,IL 60009. NR 17 TC 14 Z9 14 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 1996 VL 98 IS 2 BP 297 EP 300 PN 1 PG 4 WC Pediatrics SC Pediatrics GA UZ850 UT WOS:A1996UZ85000025 ER PT J AU Perrin, J Erenberg, G LaCamera, R Nackashi, JA Poncher, JR Randall, V Ruppert, E Wachtel, RC Ziring, PR Berlin, CM May, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT AF Perrin, J Erenberg, G LaCamera, R Nackashi, JA Poncher, JR Randall, V Ruppert, E Wachtel, RC Ziring, PR Berlin, CM May, DG Notterman, DA Ward, RM Weismann, DN Wilson, GS Wilson, JT TI Medication for children with attentional disorders SO PEDIATRICS LA English DT Article ID DEFICIT DISORDER; SOCIAL-BEHAVIOR; HYPERACTIVITY; METHYLPHENIDATE; ADOLESCENTS; DESIPRAMINE AB Increasing numbers of children with attentional difficulties have been treated with medication, especially during the last 25 years, and now adolescents and adults are also being recognized with attentional difficulties. This policy statement provides information on the role and the pharmacology of medications used to treat children with attention deficit disorders. Indications and use of medications are discussed and recommended drugs and dose levels are outlined. Information on adverse effects and common side effects is presented. C1 AMER ACAD PHYS MED & REHABIL,CHICAGO,IL. US DEPT EDUC PROGRAMS,WASHINGTON,DC. US SOCIAL SECUR ADM,WASHINGTON,DC. CTR DIS CONTROL & PREVENT,CTR ENVIRONM HLTH & INJURY CONTROL,ATLANTA,GA 30341. MATERNAL & CHILD HLTH BUR,ROCKVILLE,MD. AMER ACAD PEDIAT,COMM DRUGS,ELK GROVE VILLAGE,IL. AMER ACAD CHILD & ADOLESCENT PSYCHIAT,WASHINGTON,DC. AMER MED ASSOC,CHICAGO,IL 60610. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. HLTH PROTECT BRANCH HSB,OTTAWA,ON,CANADA. CANADIAN PEDIAT SOC,OTTAWA,ON,CANADA. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. RP Perrin, J (reprint author), AMER ACAD PEDIAT,COMM CHILDREN DISABIL,141 NW POINT BLVD,ELK GROVE VILLAGE,IL 60009, USA. NR 24 TC 27 Z9 27 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 1996 VL 98 IS 2 BP 301 EP 304 PN 1 PG 4 WC Pediatrics SC Pediatrics GA UZ850 UT WOS:A1996UZ85000026 ER PT J AU Heyman, RB Adger, H Anglin, TM Fuller, PG Jacobs, EA Shah, RZ Tenenbein, M AF Heyman, RB Adger, H Anglin, TM Fuller, PG Jacobs, EA Shah, RZ Tenenbein, M TI Testing for drugs of abuse in children and adolescents SO PEDIATRICS LA English DT Article AB The American Academy of Pediatrics (AAP) recognizes the abuse of psychoactive drugs as one of the greatest problems facing children and adolescents and condemns all such use. Diagnostic testing for drugs of abuse is frequently an integral part of the pediatrician's evaluation and management of those suspected of such use. ''Voluntary screening'' is the term applied to many mass non-suspicion-based screening programs, yet such programs may not be truly voluntary as there are often negative consequences for those who choose not to take part. Participation in such programs should not be a prerequisite to participation in school activities. Involuntary testing is not appropriate in adolescents with decisional capacity-even with parental consent-and should be performed only if there are strong medical or legal reasons to do so. The AAP reaffirms its position that the appropriate response to the suspicion of drug abuse in a young person is the referral to a qualified health care professional for comprehensive evaluation. C1 NIAAA,BETHESDA,MD 20205. NIDA,LEXINGTON,KY 40583. RP Heyman, RB (reprint author), AMER ACAD CHILD & ADOLESCENT PSYCHIAT,WASHINGTON,DC, USA. NR 15 TC 34 Z9 34 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 1996 VL 98 IS 2 BP 305 EP 307 PN 1 PG 3 WC Pediatrics SC Pediatrics GA UZ850 UT WOS:A1996UZ85000027 ER PT J AU Buters, JTM Tang, BK Pineau, T Gelboin, HV Kimura, S Gonzalez, FJ AF Buters, JTM Tang, BK Pineau, T Gelboin, HV Kimura, S Gonzalez, FJ TI Role of CYP1A2 in caffeine pharmacokinetics and metabolism: Studies using mice deficient in CYP1A2 SO PHARMACOGENETICS LA English DT Article DE CYP1A2; caffeine; pharmacokinetics; metabolism; urine; knockout mice ID HUMAN-LIVER; MESSENGER-RNAS; EXPRESSION; SEQUENCE; MOUSE; CDNA; RAT; INDUCTION; GENE; IDENTIFICATION AB We investigated the involvement of CYP1A2 in the pharmacokinetics and metabolism of caffeine using mice lacking its expression (CYP1A2 -/-). The half-life of caffeine elimination from blood was seven times longer in the CYP1A2 -/- than wild-type mice, The clearance was concomitantly eight times slower. No parameter that could affect the pharmacokinetics differed between CPP1A2 -/- and wild-type mice such as creatinine for kidney function; alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and bilirubin for liver function; or albumin for protein binding. Other P450s CYP2A, 2B, 2C, 2E1, and 3A were also unchanged in the knockout animals. Caffeine 3-demethylated metabolites thought previously to be characteristic of CYP1A2 (especially l-methylxanthine and 1-methylurate) were also found in the urines of the CYP1A2 -/- animals, although at 40% of the level found in wild-type mice. These data indicate that the clearance of caffeine in wild-type mice is primarily det ermined by CYP1A2. C1 UNIV TORONTO,DEPT PHARMACOL,TORONTO,ON M5S 1A8,CANADA. RP Buters, JTM (reprint author), NCI,BETHESDA,MD 20892, USA. RI Buters, Jeroen/G-5070-2011 NR 29 TC 59 Z9 59 U1 1 U2 5 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD AUG PY 1996 VL 6 IS 4 BP 291 EP 296 DI 10.1097/00008571-199608000-00002 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA VE720 UT WOS:A1996VE72000002 PM 8873215 ER PT J AU JurimaRomet, M Goldstein, JA LeBelle, M Aubin, RA Foster, BC Walop, W Rode, A AF JurimaRomet, M Goldstein, JA LeBelle, M Aubin, RA Foster, BC Walop, W Rode, A TI CYP2C19 genotyping and associated mephenytoin hydroxylation polymorphism in a Canadian Inuit population SO PHARMACOGENETICS LA English DT Article DE CYP2C19; genotype; phenotype; Inuit ID S-MEPHENYTOIN; OXIDATION POLYMORPHISM; GENETIC POLYMORPHISMS; CAUCASIAN POPULATIONS; R-MEPHENYTOIN; DEBRISOQUIN; METABOLISM; DEFICIENCY; PHENOTYPE; JAPANESE AB The CYP2C19-associated oxidation polymorphism of mephenytoin was investigated in an Inuit population living in the high Arctic of Canada, Results were obtained for 152 subjects, of whom 90 were unrelated to first degree relatives. Phenotyping was based on the capillary gas chromatographic determination of the S/R enantiomeric ratio in overnight urine collected after a dose of 100 mg (R,S)-mephenytoin. The phenotype was confirmed by determining the SIR enantiomeric ratio after acid treatment of urine samples, and for some subjects, by determining urinary recovery of 4'-hydroxymephenytoin using capillary electrophoresis analysis. DNA was analysed for the mi and m2 mutations of CYP2C19. Three of 152 subjects (2.0%; 95% confidence limits: 0.0-4.2%) were phenotypically classified as poor metabolizers (PMs), Genotype analysis characterized three individuals as homozygous, and 28 individuals as heterozygous for the mi mutation, the remaining individuals being homozygous for the wild-type allele. The genotype of the three PMs was concordant with that of the phenotype. DNA fingerprinting confirmed that these three individuals were genetically unrelated. The allele frequency of the CYPZC19(m1) mutation, determined in unrelated subjects, was 0.12 (95% confidence limits: 0.07-0.17). CYP2C19(m2) was not detected in this population, Thus, the Canadian Inuit resemble Caucasian rather than Asian populations in both the incidence of PM phenotype and the molecular basis of the polymorphism. C1 NIEHS,RES TRIANGLE PK,NC 27709. DEPT HLTH & WELF,BUR DRUG POLICY & COORDINAT,DRUGS DIRECTORATE,HLTH PROTECT BRANCH,OTTAWA,ON K1A 0L2,CANADA. UNIV TORONTO,SCH PHYS & HLTH EDUC,TORONTO,ON M5S 1A8,CANADA. RP JurimaRomet, M (reprint author), DEPT HLTH & WELF,BUR DRUG RES,DRUGS DIRECTORATE,HLTH PROTECT BRANCH,BANTING RES CTR 2201C,OTTAWA,ON K1A 0L2,CANADA. RI Goldstein, Joyce/A-6681-2012 NR 46 TC 22 Z9 25 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD AUG PY 1996 VL 6 IS 4 BP 329 EP 339 DI 10.1097/00008571-199608000-00006 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA VE720 UT WOS:A1996VE72000006 PM 8873219 ER PT J AU SullivanKlose, TH Ghanayem, BI Bell, DA Zhang, ZY Kaminsky, LS Shenfield, GM Miners, JO Birkett, DJ Goldstein, JA AF SullivanKlose, TH Ghanayem, BI Bell, DA Zhang, ZY Kaminsky, LS Shenfield, GM Miners, JO Birkett, DJ Goldstein, JA TI The role of the CYP2C9-Leu(359) allelic variant in the tolbutamide polymorphism SO PHARMACOGENETICS LA English DT Article DE CYP2C9; tolbutamide; polymorphism ID CYP2C SUBFAMILY; (S)-MEPHENYTOIN 4'-HYDROXYLASE; CYTOCHROME-P-450; DEBRISOQUINE; MEPHENYTOIN; METABOLISM; GENE; 4-HYDROXYLASE; HYDROXYLATION; EXPRESSION AB Tolbutamide undergoes hydroxylation in humans via a cytochrome P450-mediated pathway, The primary P450 isozyme responsible for this metabolism is thought to be CYP2C9, Population studies have indicated the existence of slow metabolizers of tolbutamide (similar to 1 in 500) suggesting a rare polymorphism associated with 2C9, Several allelic variants of 2C9 have been identified; however, the effect of these allelic variations on metabolism in vivo is not established, In the present study, the coding regions, intron-exon junctions, and upstream region of CYP2C9 were amplified by PCR and sequenced in two slow metabolizers. One individual was homozygous for Leu(359)/Leu(359) and the other individual was heterozygous for Arg(144)/Cys(144) and for Ile(359)/Leu(359), No other genetic variations in 2C9 were detected in these individuals, PCR-RFLP tests showed that Arg(144)Tyr(358)Ile(359)Gly(417) is the principle CYP2C9 allele, Frequencies of the rarer Leu(359) and Cys(144) alleles were 0.06 and 0.08, respectively, in a Caucasian-American population and 0.005 and 0.01 respectively in African-Americans. The freqnency of the Leu(359) allele was 0.026 in Chinese-Taiwanese, but the Cys(144) allele was not detected in this population, Studies in a recombinant yeast expression system showed that the Leu(359) variant had the highest K-m and the lowest V-mac for hydroxylation of tolbutamide of all the CYP2C9 allelic variants, This allelic variant also had the highest K-m for the 7-hydroxylation of S-warfarin, The present data suggest that the incidence of the Leu(359) allelic variant of CYP2C9 may account for the occurrence of poor metabolizers of tolbutamide. C1 NIEHS,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,ALBANY,NY 12201. ROYAL N SHORE HOSP,DEPT CLIN PHARMACOL,ST LEONARDS,NSW 2065,AUSTRALIA. FLINDERS UNIV S AUSTRALIA,DEPT CLIN PHARMACOL,ADELAIDE,SA 5042,AUSTRALIA. RI Goldstein, Joyce/A-6681-2012 FU NIEHS NIH HHS [P01 ESO4238] NR 38 TC 479 Z9 505 U1 0 U2 7 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD AUG PY 1996 VL 6 IS 4 BP 341 EP 349 DI 10.1097/00008571-199608000-00007 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA VE720 UT WOS:A1996VE72000007 PM 8873220 ER PT J AU Edeki, TI Goldstein, JA deMorais, SMF Hajiloo, L Butler, M Chapdelaine, P Wilkinson, GR AF Edeki, TI Goldstein, JA deMorais, SMF Hajiloo, L Butler, M Chapdelaine, P Wilkinson, GR TI Genetic polymorphism of S-mephenytoin 4'-hydroxylation in African-Americans SO PHARMACOGENETICS LA English DT Article DE mephenytoin; African-American; genetic polymorphism; CYP2C19 ID CHINESE SUBJECTS; HYDROXYLATION; METABOLISM; POPULATION; (S)-MEPHENYTOIN; OXIDATION; FREQUENCY; 4-HYDROXYLATION; DISPOSITION; DEBRISOQUIN C1 MEHARRY MED COLL,DEPT PHARMACOL,CLIN PHARMACOL SECT,NASHVILLE,TN 37208. MEHARRY MED COLL,DEPT FAMILY & PREVENT MED,CLIN PHARMACOL SECT,NASHVILLE,TN 37208. NIEHS,RES TRIANGLE PK,NC 27709. VANDERBILT UNIV,DEPT PHARMACOL,NASHVILLE,TN 37232. RI Goldstein, Joyce/A-6681-2012 FU FDA HHS [FD-T 000888]; NIGMS NIH HHS [GM 31304] NR 28 TC 41 Z9 41 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD AUG PY 1996 VL 6 IS 4 BP 357 EP 360 DI 10.1097/00008571-199608000-00009 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA VE720 UT WOS:A1996VE72000009 PM 8873222 ER PT J AU Sills, TL Vaccarino, FJ AF Sills, TL Vaccarino, FJ TI Individual differences in sugar consumption following systemic or intraaccumbens administration of low doses of amphetamine in nondeprived rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE individual differences; feeding; sugar; nucleus accumbens; rat ID NUCLEUS ACCUMBENS AMPHETAMINE; EXTRACELLULAR DOPAMINE; LOCOMOTOR RESPONSE; NOVELTY PREDICTS; FOOD-INTAKE; FENFLURAMINE; MECHANISMS; COCAINE; ANOREXIA; REWARD AB Rats exhibit individual differences in their propensity to ingest sucrose and in their feeding response to low doses of amphetamine (AMP). Rats with high baseline sugar intake (HIGH) show a decrease in sugar consumption in response to AMP, while rats with low baseline sugar intake (LOW) show an increase in consumption (33,34). At present, it is not known whether LOW and HIGH rats would be differentially responsive to higher, anorexigenic doses of AMP. Thus. the present study was developed to further determine the dose-response curve for AMP's effects on sugar consumption in LOW and HIGH rats. One group of rats received IP injections of 0.05, 0.1, and 0.2 mg/kg AMP, while a second group was administered 0.25, 0.5, and 1.0 mg/kg AMP. A third group of rats received intranucleus accumbens (Acc) microinjections of low to moderate (2.0-8.0 mu g) doses of AMP, because evidence indicates that this may be an important site of action for AMP's effects on feeding in LOW and HIGH rats. Results showed that at low doses (less than or equal to 0.25 mg/kg), AMP stimulated sugar consumption in LOW rats and either had no effect or inhibited consumption in HIGH rats. At doses greater than 0.25 mg/kg, AMP inhibited sugar consumption in both LOW and HIGH rats. Furthermore, intra-Acc administration of AMP stimulated sugar intake in LOW rats and produced a slight, but nonsignificant, decrease in consumption in HIGH rats. Taken together, these results show that LOW and HIGH rats exhibit individual differences in their feeding response to low but not moderate to high doses of AMP. Furthermore, the evidence indicates that the Ace is an important site for AMP's facilitatory effect on sugar consumption in LOW rats. C1 NIMH,SECT BEHAV NEUROPHARMACOL,BETHESDA,MD 20892. UNIV TORONTO,DEPT PSYCHOL,TORONTO,ON M5S 1A1,CANADA. UNIV TORONTO,DEPT PSYCHIAT,TORONTO,ON,CANADA. NR 36 TC 23 Z9 23 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD AUG PY 1996 VL 54 IS 4 BP 665 EP 670 DI 10.1016/0091-3057(96)00024-X PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA VA074 UT WOS:A1996VA07400005 PM 8853187 ER PT J AU Furumura, M Sakai, C AbdelMalek, Z Barsh, GS Hearing, VJ AF Furumura, M Sakai, C AbdelMalek, Z Barsh, GS Hearing, VJ TI The interaction of agouti signal protein and melanocyte stimulating hormone to regulate melanin formation in mammals SO PIGMENT CELL RESEARCH LA English DT Review DE pigmentation; melanogenesis; MSH; agouti ID PROOPIOMELANOCORTIN-DERIVED PEPTIDES; HAIR FOLLICULAR MELANOCYTES; CULTURED HUMAN MELANOCYTES; TYROSINASE-RELATED PROTEIN; RNA DIFFERENTIAL DISPLAY; FIBROBLAST GROWTH-FACTOR; COAT-COLOR MUTANTS; MOLECULAR-CLONING; MELANOCORTIN RECEPTOR; MOUSE MELANOMA AB Important regulatory controls of melanogenesis that operate at the subcellular level to modulate the structural and/or the functional nature of the melanins and melanin granules produced in melanocytes are reviewed. Melanocyte stimulating hormone and agouti signal protein have antagonistic roles and possibly opposing mechanisms of action in the melanocyte. In the mouse, melanocyte stimulating hormone promotes melanogenic enzyme function and elicits increases in the amount of eumelanins produced, while agouti signal protein reduces total melanin production and elicits the synthesis of pheomelanin rather than eumelanin. We are now beginning to understand the complex controls involved in regulating this switch at the molecular and biochemical levels. The quality and quantity of melanins produced by melanocytes have important physiological consequences for melanocyte function and undoubtedly play important roles in the various functions of the melanins per se, including hair and skin coloration and photoprotection. C1 NIH, NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. UNIV CINCINNATI, DEPT DERMATOL, CINCINNATI, OH 45267 USA. STANFORD UNIV, HOWARD HUGHES MED INST, SCH MED, DEPT PEDIAT, STANFORD, CA 94305 USA. NR 133 TC 43 Z9 46 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD AUG PY 1996 VL 9 IS 4 BP 191 EP 203 DI 10.1111/j.1600-0749.1996.tb00109.x PG 13 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA VT668 UT WOS:A1996VT66800005 PM 8948501 ER PT J AU Hartley, RW Both, V Hebert, EJ Homerova, D Jucovic, M Nazarov, V Rybajlak, I Sevcik, J AF Hartley, RW Both, V Hebert, EJ Homerova, D Jucovic, M Nazarov, V Rybajlak, I Sevcik, J TI Barstar inhibits extracellular ribonucleases of Streptomyces and allows their production from recombinant genes SO PROTEIN AND PEPTIDE LETTERS LA English DT Article ID BARNASE; MUTAGENESIS; RECOGNITION; ENERGETICS; STABILITY AB Barstar, the intracellular protein of Bacillus amyloliquefaciens which binds to and inhibits barnase, the extracellular ribonuclease of the same organism, has been found to bind to and inhibit also the homologous ribonucleases of several Streptomyces strains. The ribonucleases of four strains of Streptomyces have been produced from recombinant or synthetic genes on plasmid vectors in E. coli. Sequence identity among these enzymes is from 49% to 69%. Sequence identities to barnase are no more than 25%. C1 NIDDKD,CELLULAR & DEV BIOL LAB,NIH,BETHESDA,MD 20892. SLOVAK ACAD SCI,INST MOL BIOL,BRATISLAVA 84251,SLOVAKIA. TEXAS A&M UNIV,DEPT MED BIOCHEM,COLLEGE STN,TX 77843. NR 19 TC 11 Z9 11 U1 0 U2 1 PU BENTHAM SCIENCE PUBL BV PI SCHIPHOL PA PO BOX 75676, 1118 ZS SCHIPHOL, NETHERLANDS SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PD AUG PY 1996 VL 3 IS 4 BP 225 EP 231 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VF757 UT WOS:A1996VF75700002 ER PT J AU Qoronfleh, MW Ho, T Banks, T Pulvino, T Brake, P Ciccarelli, R Koehn, J Huang, J Wahl, R AF Qoronfleh, MW Ho, T Banks, T Pulvino, T Brake, P Ciccarelli, R Koehn, J Huang, J Wahl, R TI Mutagenesis of recombinant human fibroblast stromelysin C-terminus reveals the autodegradation pathway SO PROTEIN AND PEPTIDE LETTERS LA English DT Article ID MATRIX METALLOPROTEINASE-3 STROMELYSIN; RHEUMATOID SYNOVIAL FIBROBLASTS; CATALYTIC DOMAIN; SUBSTRATE-SPECIFICITY; GENE FAMILY; COLLAGENASE; PURIFICATION; EXPRESSION; TISSUE; ACTIVATION AB Stromelysin as a member of the matrix metalloproteinases (MMP) family participates in connective tissue remodeling and diseases. Understanding MMPs' catalytic mechanism and designing specific inhibitors to control their activity is of great interest. A clone for mature truncated stromelysin (SL), F-83 to T-260, without the C-terminal hemopexin-like domain was constructed and expressed in E. coli. The purified, recombinant protein was active and had a specific activity and K-i values comparable to that of the native enzyme. However, protein degradation was observed which was attributed to autolysis. A specific autolytic site at S-244-L(245) was identified by N-terminal sequencing. A series of SL muteins and new truncations were engineered to evaluate their effects on autolysis. The replacement of L(245) with an R prevents the autodegradation of SL at the S-244-L(245) autolytic site. This substitution reveals the primary site initiating SL autolysis (self-catalyzed cleavage) and locates it at V-163-L(164). C1 STERLING WINTHROP RES INST,PHARMACEUT,COLLEGEVILLE,PA 19426. NCI,SAIC FREDERICK,FCRDC,FREDERICK,MD 21702. NR 34 TC 2 Z9 2 U1 0 U2 0 PU BENTHAM SCIENCE PUBL BV PI SCHIPHOL PA PO BOX 75676, 1118 ZS SCHIPHOL, NETHERLANDS SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PD AUG PY 1996 VL 3 IS 4 BP 233 EP 240 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VF757 UT WOS:A1996VF75700003 ER PT J AU Yang, LH Ahmed, SA Miles, EW AF Yang, LH Ahmed, SA Miles, EW TI PCR mutagenesis and overexpression of tryptophan synthase from Salmonella typhimurium: On the roles of beta(2) subunit Lys-382 SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID SITE-DIRECTED MUTAGENESIS; ESCHERICHIA-COLI; ALPHA-SUBUNIT; BINDING-SITE; GENE PAIR; EXPRESSION; COMPLEX; SYNTHETASE; MECHANISM; VECTORS AB We have devised convenient methods for mutagenesis and very high level expression of wild type and mutant tryptophan synthase alpha and beta(2) subunits and alpha(2) beta(2) complex from Salmonella typhimurium, The trpBA genes were modified by introduction of five new restriction sites by polymerase chain reaction (PCR) and mere then cloned into the plasmid pTrc99A under trc promoter control. The recombinant plasmid pEBA-10 and three plasmids constructed from pEBA-10 were transformed into Escherichia coli CB149, which lacks tryptophan operon genes. Optimization of growth conditions of the transformed cells resulted in 10- to 40-fold higher yields of cells (similar to 22 g/liter) than attained previously. The improved expression system gave higher yields of tryptophan synthase proteins (23-70% of the soluble protein) and led to correspondingly high yields of purified alpha and beta(2) subunits or alpha(2) beta(2) complex (200-800 mg/liter). A plasmid containing 8 copies of the trpA gene gave the highest yield of alpha subunit. The PCR-based mutagenesis method permits mutation of any base pair in the trpBA genes, between suitable pairs of restriction sites, and requires only one new primer per mutation, The method is illustrated by construction of mutant beta(2) subunits with any of five amino acid substitutions at Lys-382, the site of a previously described missense mutation. Characterization of the purified mutant alpha(2) beta(2) complexes shows that Lys-382 in the wild type alpha(2) beta(2) complex does not serve an essential catalytic role but may stabilize an active ''closed'' conformation of the enzyme by forming a salt bridge with Glu-350. C1 NIDDKD,ENZYME STRUCT & FUNCT SECT,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 30 TC 40 Z9 42 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD AUG PY 1996 VL 8 IS 1 BP 126 EP 136 DI 10.1006/prep.1996.0082 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA VB961 UT WOS:A1996VB96100015 PM 8812843 ER PT J AU Gustchina, A Kervinen, J Powell, DJ Zdanov, A Kay, J Wlodawer, A AF Gustchina, A Kervinen, J Powell, DJ Zdanov, A Kay, J Wlodawer, A TI Structure of equine infectious anemia virus proteinase complexed with an inhibitor SO PROTEIN SCIENCE LA English DT Article DE AIDS; proteinase; retroviruses; specificity; structure ID HIV-1 PROTEASE; IMMUNODEFICIENCY-VIRUS; CRYSTAL-STRUCTURE; BINDING; RESISTANCE; SPECIFICITY; VARIANTS; CLEAVAGE; SITE AB Equine infectious anemia virus (EIAV), the causative agent of infectious anemia in horses, is a member of the lentiviral family. The virus-encoded proteinase (PR) processes viral polyproteins into functional molecules during replication and it also cleaves viral nucleocapsid protein during infection. The X-ray structure of a complex of the I54G mutant of EIAV PR with the inhibitor HBY-793 was solved at 1.8 Angstrom resolution and refined to a crystallographic R-factor of 0.136. The molecule is a dimer in which the monomers are related by a crystallographic twofold axis. Although both the enzyme and the inhibitor are symmetric, the interactions between the central part of the inhibitor and the active site aspartates are asymmetric, and the inhibitor and the two flaps are partially disordered. The overall fold of EIAV PR is very similar to that of other retroviral proteinases. However, a novel feature of the EIAV PR structure is the appearance of the second cr-helix in the monomer in a position predicted by the structural template for the family of aspartic proteinases. The parts of the EIAV PR with the highest resemblance to human immunodeficiency virus type 1 PR include the substrate-binding sites; thus, the differences in the specificity of both enzymes have to be explained by enzyme-ligand interactions at the periphery of the active site as well. C1 NCI, ABL BASIC RES PROGRAM, FREDERICK CANC RES & DEV CTR, MACROMOL STRUCT LAB, FREDERICK, MD 21702 USA. UNIV WALES COLL CARDIFF, SCH MOL & MED BIOSCI, CARDIFF CF1 3US, S GLAM, WALES. NR 43 TC 36 Z9 37 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 1996 VL 5 IS 8 BP 1453 EP 1465 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VA138 UT WOS:A1996VA13800002 PM 8844837 ER PT J AU Zhu, PP Peterkofsky, A AF Zhu, PP Peterkofsky, A TI Sequence and organization of genes encoding enzymes involved in pyruvate metabolism in Mycoplasma capricolum SO PROTEIN SCIENCE LA English DT Article DE acetate kinase; dihydrolipoamide dehydrogenase; lipoate-protein ligase; NADH oxidase; PTS; phosphotransacetylase; pyruvate dehydrogenase ID ALPHA-KETOACID DEHYDROGENASE; AMINO-ACID-SEQUENCES; SUGAR PHOSPHOTRANSFERASE SYSTEM; CHAIN-OXOACID DEHYDROGENASE; SOMATIC E1-ALPHA SUBUNIT; SYRUP-URINE-DISEASE; MOLECULAR-CLONING; NUCLEOTIDE-SEQUENCE; DIHYDROLIPOAMIDE DEHYDROGENASE; LIPOAMIDE DEHYDROGENASE AB The region of the genome of Mycoplasma capricolum upstream of the portion encompassing the genes for Enzymes zymes I and IIA(glc) of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) was cloned and sequenced. Examination of the sequence revealed open reading frames corresponding to numerous genes involved with the oxidation of pyruvate. The deduced gene organization is naox (encoding NADH oxidase)-lplA (encoding lipoate-protein ligase)-odpA (encoding pyruvate dehydrogenase EI alpha)-odpB (encoding pyruvate dehydrogenase EI beta)-odp2 (encoding pyruvate dehydrogenase EII)-dldH (encoding dihydrolipoamide dehydrogenase)-pta (encoding phosphotransacetylase)-ack (encoding acetate kinase)-orfA (an unknown open reading frame)-kdtB-ptsI-crr. Analysis of the DNA sequence suggests that the naox and lplA genes are part of a single operon, odpA and odpB constitute an additional operon, odp2 and dldH a third operon, and pfa and ack an additional transcription unit. Phylogenetic analyses of the protein products of the odpA and odpB genes indicate that they are most similar to the corresponding proteins from Mycoplasma genitalium, Acholeplasma laidlawii, and Gram-positive organisms. The product of the odp2 gene contains a single lipoyl domain, as is the case with the corresponding proteins from M. genitalium and numerous other organisms. An evolutionary tree places the M. capricolum odp2 gene product in close relationship to the corresponding proteins from A. laidlawii and M. genitalium. The dldH gene encodes an unusual form of dihydrolipoamide dehydrogenase that contains an aminoterminal extension corresponding to a lipoyl domain, a property shared by the corresponding proteins from Alcaligenes eutrophus and Clostridium magnum. Aside from that feature, the protein is related phylogenetically to the corresponding proteins from A. laidlawii and M. genitalium. The phosphotransacetylase from M. capricolum is related most closely to the corresponding protein from M. genitalium and is distinguished easily from the enzymes from Escherichia coli and Haemophilus influenzae by the absence of the characteristic amino-terminal extension. The acetate kinase from M. capricolum is related evolutionarily to the homologous enzyme from M. genitalium. Map position comparisons of genes encoding proteins involved with pyruvate metabolism show that, whereas all the genes are clustered in M. capricolum, they are scattered in M. genitalium. C1 NHLBI, LAB BIOCHEM GENET, BETHESDA, MD 20892 USA. NR 84 TC 20 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD AUG PY 1996 VL 5 IS 8 BP 1719 EP 1736 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VA138 UT WOS:A1996VA13800025 PM 8844861 ER PT J AU Kaufman, S AF Kaufman, S TI Experiencing classical enzymology in its prime SO PROTEIN SCIENCE LA English DT Editorial Material RP Kaufman, S (reprint author), NIMH,NEUROCHEM LAB,NIH,BLDG 36-3D30,36 CONVENT DR,MSC 4096,BETHESDA,MD 20892, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD AUG PY 1996 VL 5 IS 8 BP 1742 EP 1746 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VA138 UT WOS:A1996VA13800027 PM 8844862 ER PT J AU Wallqvist, A Covell, DG AF Wallqvist, A Covell, DG TI Docking enzyme-inhibitor complexes using a preference-based free-energy surface SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE surface complementarity; macromolecular interactions; HIV-1 protease inhibitor binding ID PROTEIN-PROTEIN RECOGNITION; FAVORABLE BINDING-SITES; MONTE-CARLO DOCKING; COPY SIMULTANEOUS SEARCH; HYDROGEN-BOND FUNCTIONS; MOLAR HEAT-CAPACITY; LIGAND PROBE GROUPS; MOLECULAR RECOGNITION; SHAPE COMPLEMENTARITY; AUTOMATED DOCKING AB We present a docking scheme that utilizes both a surface complementarity screen as well as an energetic criterion based on surface area burial. Twenty rigid enzyme/inhibitor complexes with known coordinate sets are arbitrarily separated and reassembled to an average all-atom rms (root mean square) deviation of 1.0 Angstrom from the native complexes. Docking is accomplished by a hierarchical search of geometrically compatible triplets of surface normals on each molecule. A pruned tree of possible bound configurations is built up using successive consideration of larger and larger triplets. The best scoring configurations are then passed through a free-energy screen where the lowest energy member is selected as the predicted native state. The free energy approximation is derived from observations of surface burial by atom pairs across the interface of known enzyme/inhibitor complexes. The occurrence of specific atom-atom surface burial, for a set of complexes with well-defined secondary structure both in the bound and unbound states, is parameterized to mimic the free energy of binding. The docking procedure guides the inhibitor into its native state using orientation and distance-dependent functions that reproduce the ideal model of free energies with an average rms deviation of 0.9 kcal/mol, For all systems studied, this docking procedure identifies a single, unique minimum energy configuration that is highly compatible with the native state. (C) 1996 Wiley-Liss, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,NCI,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NR 90 TC 37 Z9 38 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD AUG PY 1996 VL 25 IS 4 BP 403 EP 419 DI 10.1002/(SICI)1097-0134(199608)25:4<403::AID-PROT1>3.0.CO;2-E PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VC586 UT WOS:A1996VC58600002 PM 8865336 ER PT J AU Bettati, S Mozzarelli, A Rossi, GL Tsuneshige, A Yonetani, T Eaton, WA Henry, ER AF Bettati, S Mozzarelli, A Rossi, GL Tsuneshige, A Yonetani, T Eaton, WA Henry, ER TI Oxygen binding by single crystals of hemoglobin: The problem of cooperativity and inequivalence of alpha and beta subunits SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE nickel-iron hybrid hemoglobins; two-state allosteric model; single crystal absorption spectra; Bohr effect; multisubunit proteins; quaternary structure ID 82-BETA-2 LYSYL RESIDUES; HUMAN ADULT HEMOGLOBIN; STATE HUMAN-HEMOGLOBIN; LIGANDED T-STATE; EQUILIBRIUM PROPERTIES; HYBRID HEMOGLOBINS; MODEL; DEOXY; STEREOCHEMISTRY; RESOLUTION AB Oxygen binding by the human hemoglobin tetramer in the T quaternary structure is apparently noncooperative in the crystalline state (Hill n=1.0), as predicted by the two-state allosteric model of Monod, Wyman, and Changeux (MWC) (Mozzarelli et al., Nature 351:416-419, 1991; Rivetti et al., Biochemistry 32:2888-2906, 1993). However, cooperativity within the tetramer can be masked by a difference in affinity between the alpha and beta subunits. Indeed, analysis of the binding curves derived from absorption of light polarized along two different crystal directions, for which the projections of the alpha and beta hemes are slightly different, revealed an inequivalence in the intrinsic oxygen affinity of the alpha and beta subunits (p50(alpha) approximate to 80 torr, p50(beta) = 370 torr at 15 degrees C) that compensates a small amount of cooperativity (Rivetti et al., Biochemistry 32:2888-2906, 1993). To further investigate this problem, we have measured oxygen binding curves of single crystals of hemoglobin (in a different lattice) in which the iron in the a subunits has been replaced by the non-oxygen-binding nickel(II). The Hill n is 0.90+/-0.06, and the p50 is slightly different for light polarized parallel to different crystal directions, indicating a very small difference in affinity between the two crystallographically inequivalent beta subunits. The average crystal p50 is 110+/-20 torr at 15 degrees C, close to the p50 of 80 torr observed in solution, but about threefold less than the p50 calculated by Rivetti et al. (Biochemistry 32:2888-2906, 1993) for the beta subunits of the unsubstituted tetramer. These results suggest that Rivetti et al., if anything, overestimated the alpha/beta inequivalence. They therefore did not underestimate the cooperativity within the T quaternary structure, when they concluded that it represents a small deviation from the perfectly noncooperative binding of an MWC allosteric model. Our conclusion of nearly perfect MWC behavior for binding to the T state of unmodified hemoglobin raises the question of the relevance of the large T-state cooperativity inferred for cyanide binding to partially oxidized hemoglobin (Ackers et al., Science 255:54-63, 1992). (C) 1996 Wiley-Liss, Inc. C1 UNIV PARMA,INST BIOCHEM SCI,I-43100 PARMA,ITALY. UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RI Mozzarelli, Andrea/C-3615-2014; Henry, Eric/J-3414-2013 OI Mozzarelli, Andrea/0000-0003-3762-0062; Henry, Eric/0000-0002-5648-8696 FU NHLBI NIH HHS [HL14508] NR 34 TC 28 Z9 28 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD AUG PY 1996 VL 25 IS 4 BP 425 EP 437 DI 10.1002/prot.3 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VC586 UT WOS:A1996VC58600004 PM 8865338 ER PT J AU Peat, TS Frank, EG Woodgate, R Hendrickson, WA AF Peat, TS Frank, EG Woodgate, R Hendrickson, WA TI Production and crystallization of a selenomethionyl variant of UmuD', an Escherichia coli SOS response protein SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE MAD phasing; mutagenesis; autodigestion; replication; dimerization; X-ray crystallography ID DNA POLYMERASE-III; RECA PROTEIN; ANOMALOUS DIFFRACTION; MUTAGENESIS PROTEINS; LEXA REPRESSOR; CLEAVAGE; UV; REPAIR; PURIFICATION; HOMOLOGY AB Crystals of both native and mutant Escherichia coli UmuD' protein were obtained using the hanging drop method, Soaking the native crystals in solutions of heavy metal ions failed to produce good isomorphous derivatives, and selenomethionine substituted wild-type protein did not crystallize under conditions that gave native crystals, Site-directed mutagenesis was used to change the penultimate residue, a methionine amino acid, to either a value or a threonine amino acid, Crystals were subsequently obtained from these mutant proteins with and without selenomethionine incorporation, Crystals of the native, the mutant, and the selenomethionine incorporated protein were all similar, crystallizing in the P4(1)2(1)2 space group. (C) 1996 Wiley-Liss, Inc. C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT BIOCHEM & MOL BIOPHYS,NEW YORK,NY 10032. COLUMBIA UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10032. NICHHD,SECT DNA REPLICAT REPAIR & MUTAGENESIS,NIH,BETHESDA,MD 20892. RI Peat, Thomas/F-9817-2010 OI Peat, Thomas/0000-0002-6488-0831 FU NIGMS NIH HHS [GM34102] NR 32 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD AUG PY 1996 VL 25 IS 4 BP 506 EP 509 DI 10.1002/(SICI)1097-0134(199608)25:4<506::AID-PROT10>3.3.CO;2-Z PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VC586 UT WOS:A1996VC58600011 PM 8865345 ER PT J AU Huffman, LC AF Huffman, LC TI Psychophysiology research and career development: Funding opportunities at NIMH SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD AUG PY 1996 VL 33 SU 1 BP S47 EP S47 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA VF577 UT WOS:A1996VF57700185 ER PT J AU Lovelace, CT Duncan, CC Kaye, WH AF Lovelace, CT Duncan, CC Kaye, WH TI Effects of clonidine on event-related potential indices of auditory and visual information processing SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. UNIV PITTSBURGH,PITTSBURGH,PA 15260. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD AUG PY 1996 VL 33 SU 1 BP S56 EP S56 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA VF577 UT WOS:A1996VF57700223 ER PT J AU Zahn, TP AF Zahn, TP TI Autonomic correlates of diagnosis and symptoms in childhood psychopathology SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD AUG PY 1996 VL 33 SU 1 BP S9 EP S9 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA VF577 UT WOS:A1996VF57700031 ER PT J AU Ronan, RS Heinz, WF Kempner, ES AF Ronan, RS Heinz, WF Kempner, ES TI High-energy electron irradiation of proteins and nucleic acids: Collisional stopping power and average energy loss SO RADIATION AND ENVIRONMENTAL BIOPHYSICS LA English DT Article ID CHARGED-PARTICLES; CROSS-SECTIONS; ATOMS; MOLECULES AB Inactivation of proteins due to the direct action of ionizing radiation and the electron energy loss spectra of organic materials indicate that an average of 60-66 eV of energy is lost from high energy electrons in each inelastic collision with target molecules. The average energy loss per inelastic collision with high energy electrons in solid, carbon-based materials, proteins and nucleic acids is calculated from mass collisional stopping powers and empirical total inelastic cross-sections. Bragg's Additivity Law is used for the calculation of the mean excitation energy of molecules. For simple organic compounds, the calculated average energy loss is close to that obtained by direct observation of the energy loss suffered by electrons as they pass through thin films of organic material. The density effect correction for the rate of energy loss, important in the more complex case of proteins irradiated with 10 MeV electrons, is determined using the comparable mass collisional stopping power of water and proteins. In this manner, a value is obtained for the average energy per inelastic collision of high energy electrons with proteins, which is similar to the average energy per inactivating event of proteins. Analogous calculations for nucleic acids are also presented. C1 NIAMSD,PHYS BIOL LAB,NIH,BETHESDA,MD 20892. NR 21 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-634X J9 RADIAT ENVIRON BIOPH JI Radiat. Environ. Biophys. PD AUG PY 1996 VL 35 IS 3 BP 159 EP 162 DI 10.1007/s004110050025 PG 4 WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging GA VF198 UT WOS:A1996VF19800005 PM 8880957 ER PT J AU Burleson, FG Simeonova, PP Germolec, DR Luster, MI AF Burleson, FG Simeonova, PP Germolec, DR Luster, MI TI Dermatotoxic chemical stimulate of c-jun and c-fos transcription and AP-1 DNA binding in human keratinocytes SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; PROTOONCOGENE EXPRESSION; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; SKIN-DISEASE; MOUSE SKIN; ACTIVATION; INDUCTION; CYTOKINE; DIFFERENTIATION AB In many organ/tissues rapid and transient increases in early-immediate gene responses, such as those that encode for the AP-1 family of transcription factors, occur in response to exogenous stimuli. Activation of AP-1, in turn, helps regulate the expression of genes involved in cell growth, inflammatory responses, and repair processes. In the present studies, we demonstrate that increases in AP-1 DNA binding activity, as well as c-jun and c-fos mRNA levels, occur in human keratinocytes in response to diverse dermatotoxic chemicals, including phenol and arsenic as well as phorbol ester, the latter employed as a positive control. The AP-1 DNA binding complex has affinity for the consensus AP-1 sequence but not the CRE2 binding sequence of the proenkephalin promoter or the NF kappa B consensus sequence indicating that the response is relatively specific. The binding complex is composed of Jun:Fos heterodimers, including Jun B and Jun D. Evidence is provided suggesting that AP-1 binding is associated with an increase in IL-1 alpha expression, an early mediator of toxic response in the skin. C1 NIOSH,TOXICOL & MOL BIOL BRANCH,MORGANTOWN,WV 26505. NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,NIH,RES TRIANGLE PK,NC 27709. NR 35 TC 27 Z9 27 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 SN 1078-0297 J9 RES COMMUN MOL PATH JI Res. Commun. Mol. Pathol. Pharmacol. PD AUG PY 1996 VL 93 IS 2 BP 131 EP 148 PG 18 WC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy GA VJ565 UT WOS:A1996VJ56500001 PM 8884985 ER PT J AU Leveck, ML Jones, CB AF Leveck, ML Jones, CB TI The nursing practice environment, staff retention, and quality of care SO RESEARCH IN NURSING & HEALTH LA English DT Article ID JOB-SATISFACTION; NURSES; OUTCOMES; CLIMATE AB The effects of key factors in the nursing practice environment-management style, group cohesion, job stress, organizational job satisfaction, and professional job satisfaction-on staff nurse retention and process aspects of quality of care were examined. Hinshaw and Atwood's (1985) anticipated turnover model was modified and expanded to include relevant antecedent and outcome variables. The four-stage theoretical model was tested using data from 50 nursing units at four acute care hospitals in the southeast. The model explained 49% of the variance in staff nurse retention and 39% of the variance in process aspects of quality of nursing care. Study findings warrant careful consideration in light of recent practice environment changes:experience on the unit and professional job satisfaction were predictors of staff nurse retention; job stress and clinical service were predictors of quality of care. The variable contributing the most to indirect, and in turn, total model effects, was that of management style. These results substantiate the belief that aspects of the practice environment affect staff nurse retention, and most importantly, the quality of care delivered on hospital nursing units. (C) 1996 John Wiley & Sons, Inc. C1 UNIV VIRGINIA,SCH NURSING,CHARLOTTESVILLE,VA 22903. NINR,NIH,BETHESDA,MD. FU NINR NIH HHS [K07 NR00008] NR 54 TC 118 Z9 124 U1 2 U2 8 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD AUG PY 1996 VL 19 IS 4 BP 331 EP 343 DI 10.1002/(SICI)1098-240X(199608)19:4<331::AID-NUR7>3.0.CO;2-J PG 13 WC Nursing SC Nursing GA UY604 UT WOS:A1996UY60400008 PM 8773556 ER PT J AU Ermentrout, GB Rinzel, J AF Ermentrout, GB Rinzel, J TI Reflected waves in an inhomogeneous excitable medium SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE echo waves; excitable media; cable equations ID REENTRANT ARRHYTHMIAS; PROPAGATION; MECHANISM; EXCITATION; EQUATIONS; IMPULSES; FIBERS; MUSCLE AB Propagation can be encumbered in an excitable cable in which intrinsic properties change abruptly. A sudden increase in diameter or a decrease in conductivity or excitability can lead to propagation block or delay in propagation with or without reflection. We study such transient phenomena from a geometric point of view. A simple two-cell caricature, with one cell enlarged to mimic diameter increase, is developed and analyzed. Our analysis indicates that reflected waves may result from the existence of an unstable periodic orbit. As the inhomogeneity parameter is varied, this unstable cycle is nearer to and then farther from the initial state that mimics an incoming wave. This fact leads to a variety of complicated reflected waves. Correspondingly, we find numerically complex sequences of reflected-transmitted waves in biophysically more realistic cable analogues. The unstable periodic orbit in the cable appears to be related to a one-dimensional spiral wave described by Kopell and Howard [Stud. Appl. Math., 64 (1981), pp. 1-56]. Finally, we argue that reflection phenomena occur more robustly when excitability is due to saddle-type threshold behavior (type I excitability in the sense of Rinzel and Ermentrout [in Methods in Neuronal Modeling: FP om Synapses to Networks, C. Koch and I. Segev, eds., MIT Press, Cambridge, MA, 1989]). C1 NIDDK, NIH, MATH RES BRANCH, BETHESDA, MD 20814 USA. RP Ermentrout, GB (reprint author), UNIV PITTSBURGH, DEPT MATH, PITTSBURGH, PA 15206 USA. NR 26 TC 36 Z9 36 U1 0 U2 1 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 EI 1095-712X J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD AUG PY 1996 VL 56 IS 4 BP 1107 EP 1128 DI 10.1137/S0036139994276793 PG 22 WC Mathematics, Applied SC Mathematics GA UY321 UT WOS:A1996UY32100007 ER PT J AU Longstreth, WT Manolio, TA Arnold, A Burke, GL Bryan, N Jungreis, CA Enright, PL OLeary, D Fried, L AF Longstreth, WT Manolio, TA Arnold, A Burke, GL Bryan, N Jungreis, CA Enright, PL OLeary, D Fried, L TI Clinical correlates of white matter findings on cranial magnetic resonance imaging of 3301 elderly people - The cardiovascular health study SO STROKE LA English DT Article DE aged; cognition; hypertension; magnetic resonance imaging; white matter ID VASCULAR RISK-FACTORS; MINI-MENTAL STATE; OLDER ADULTS; LESIONS; DISEASE; ROTTERDAM; DISEQUILIBRIUM; ABNORMALITIES; MRI AB Background and Purpose Our aim was to identify potential risk factors for and clinical manifestations of white matter findings on cranial MRI in elderly people. Methods Medicare eligibility lists were used to obtain a representative sample of 5888 community-dwelling people aged 65 years or older. Correlates of white matter findings were sought among 3301 participants who underwent MRI scanning and denied a history of stroke or transient ischemic attack. Participants underwent extensive standardized evaluations at baseline and on follow-up, including standard questionnaires, physical examination, multiple blood tests, electrocardiogram, pulmonary function tests, carotid sonography, and M-mode echocardiography. Neuroradiologists graded white matter findings from 0 (none) to 9 (maximal) without clinical information. Results Many potential risk factors were related to the white matter grade, but in the multivariate model the factors significantly (all P < .01) and independently associated with increased grade were greater age, clinically silent stroke on MRI, higher systolic blood pressure, lower forced expiratory volume in 1 second (FEV(1)), and income less than $50 000 per year. If excluded, FEV(1) was replaced in the model by female sex, history of smoking, and history of physician-diagnosed hypertension at the baseline examination, Many clinical features were correlated with the white matter grade, especially those indicating impaired cognitive and lower extremity function. Conclusions White matter findings were significantly associated with age, silent stroke, hypertension, FEV(1), and income. The white matter findings may not be considered benign because they are associated with impaired cognitive and lower extremity function. C1 UNIV WASHINGTON,DEPT NEUROL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,NEURORADIOL DIV,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. UNIV PITTSBURGH,MED CTR,DEPT RADIOL & NEUROL SURG,PITTSBURGH,PA. UNIV ARIZONA,CTR RESP SCI,TUCSON,AZ. TUFTS UNIV NEW ENGLAND MED CTR,DEPT RADIOL,BOSTON,MA 02111. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 22 TC 884 Z9 898 U1 2 U2 21 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 1996 VL 27 IS 8 BP 1274 EP 1282 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VA092 UT WOS:A1996VA09200002 PM 8711786 ER PT J AU Yang, L Thomas, ND Helke, CJ AF Yang, L Thomas, ND Helke, CJ TI Characterization of substance P release from the intermediate area of rat thoracic spinal cord SO SYNAPSE LA English DT Article DE coexistence; sympathetic function; intermediolateral cell column; tachykinins; NK1; receptor ID INTERMEDIOLATERAL CELL COLUMN; CENTRAL NERVOUS-SYSTEM; GENE-RELATED PEPTIDE; AUTORADIOGRAPHIC LOCALIZATION; DIFFERENTIAL RELEASE; NEUROKININ-A; RECEPTOR ANTAGONISTS; NEUROPEPTIDE-K; BINDING-SITES; SEROTONIN AB Substance P (SP) nerve terminals innervate the intermediolateral cell column (IML) of the thoracic spinal cord, where SP coexists with serotonin (5-HT), neurokinin A (NKA) and thyrotropin-releasing hormone (TRH). Neither the depolarization-induced release of SP nor the presence of other neurochemicals in the regulation of SP release has been directly studied in this system. In the present study, basal and K+-stimulated release of SP from the microdissected intermediate area (including the IML, intercalated nucleus and central autonomic nucleus) of the rat thoracic spinal cord, and the regulation of SP release by presynaptic autoreceptors and by coexisting neurochemicals (5-HT, NKA and TRH) were studied using an in vitro superfusion system. Potassium evoked a concentration- and extracellular Ca2+-dependent release of SP. In rats pretreated with the serotoninergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), both SP content and the absolute amount of SP released were decreased. However, the fraction of the remaining tissue content of SP released by K+ depolarization was not changed subsequent to 5,7-DHT treatment. Moreover, 5-HT, 5-HT1B agonists (CGS-12066B and RU 24969) and a 5-HT3 agonist (2-methyl-5-HT) did not alter the K+-evoked release of SP. These data demonstrate that SP is released from the intermediate area of the rat thoracic spinal cord and some of the SP released comes from serotoninergic nerve terminals. Although 5-HT coexists with SP in the IML, neither endogenous 5-HT nor 5-HT receptor ligands appear to regulate the release of SP. Other colocalized neuropeptides (NKA and TRH) are not involved in the regulation of SP release because neither NKA, a NK2 agonist (GR 64349) nor a TRH analog (MK-771) changed the K+-evoked release of SP. A neurokinin-1 (NK1) antagonist (GR 82334) dose-dependently (10(-9)-10(-7) M) increased the K+-stimulated release of SP. These data suggest the presence of presynaptic inhibitory NK1 autoreceptors. Whereas, NK(?)1 agonists, [GR 73632 (10(-9)-10(-6) M) and [Sar(9), Met (O-2)(11)]SP (10(-8)-10(-6) M)], increased the basal and K+-stimulated release of SP, the excitatory effects of GR 73632 were not blocked by the NK1 antagonist. Moreover, GR 73632 increased the efflus of SP to a greater extent in the absence of peptidase inhibitors. Thus, the effect of NK1 agonists on the release of SP may be related to an inhibition of peptide degradation rather than activation of NK1 autoreceptors. (C) 1996 Wiley-Liss, Inc. C1 UNIFORMED SERV UNIV HLTH SCI, DEPT PHARMACOL, BETHESDA, MD 20814 USA. UNIFORMED SERV UNIV HLTH SCI, PROGRAM NEUROSCI, BETHESDA, MD 20814 USA. NIMH, BIOL PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. FU NINDS NIH HHS [R01-NS24876] NR 43 TC 7 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 EI 1098-2396 J9 SYNAPSE JI Synapse PD AUG PY 1996 VL 23 IS 4 BP 265 EP 273 DI 10.1002/(SICI)1098-2396(199608)23:4<265::AID-SYN4>3.0.CO;2-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VA234 UT WOS:A1996VA23400004 PM 8855511 ER PT J AU Lillrank, SM Lipska, BK Bachus, SE Wood, GK Weinberger, DR AF Lillrank, SM Lipska, BK Bachus, SE Wood, GK Weinberger, DR TI Amphetamine-induced c-fos mRNA expression is altered in rats with neonatal ventral hippocampal damage SO SYNAPSE LA English DT Article DE hippocampus; in situ hybridization; c-fos mRNA; ibotenic acid; amphetamine ID MEDIAL PREFRONTAL CORTEX; IBOTENIC ACID LESIONS; IMMEDIATE-EARLY GENES; MESSENGER-RNA; INDUCED LOCOMOTION; DOPAMINE; HALOPERIDOL; NEURONS; STRIATUM; RECEPTOR AB To further characterize the mechanisms underlying enhanced dopamine-related behaviors expressed during adulthood in rats with neonatal excitotoxic ventral hippocampal (VH) damage, we studied the expression of c-fos mRNA in these rats after a single saline or amphetamine (AMPH) (10 mg/kg, i.p.) injection using in situ hybridization. The VH of rat pups was lesioned with ibotenic acid on postnatal day 7 (PD7). At the age of 90 days, rats were challenged with AMPH or saline, and the expression of c-fos mRNA using an oligonucleotide probe was assessed 30, 90, and 180 min later. AMPH significantly increased c-fos mRNA expression in medial prefrontal cortex, piriform cor-tex, cingulate cortex, septal region, and dorsolateral and ventromedial striatum in control and lesioned rats. However, this response to AMPH was attenuated 30 min after AMPH injection in all of these regions in the lesioned as compared to the sham-operated rats. No significant changes were seen at other time points. These results indicate that the neonatal VH lesion alters time-dependent intracellular signal transduction mechanisms measured by AMPH-induced c-fos mRNA expression in cortical and subcortical brain regions. Changes in c-fos mRNA expression in this putative animal model of schizophrenia may have implications for long-term alterations in cellular phenotype because of altered regulation of certain target genes. (C) 1996 Wiley-Liss, Inc. RP Lillrank, SM (reprint author), NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NEUROSCI CTR ST ELIZABETHS,WAW BLDG,WASHINGTON,DC 20032, USA. NR 44 TC 29 Z9 29 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD AUG PY 1996 VL 23 IS 4 BP 292 EP 301 DI 10.1002/(SICI)1098-2396(199608)23:4<292::AID-SYN7>3.3.CO;2-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VA234 UT WOS:A1996VA23400007 PM 8855514 ER PT J AU Cone, EJ AF Cone, EJ TI Mechanisms of drug incorporation into hair SO THERAPEUTIC DRUG MONITORING LA English DT Article; Proceedings Paper CT 4th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology CY SEP 04-08, 1995 CL VIENNA, AUSTRIA SP Int Assoc Therapeut Drug Monitoring & Clin Toxicol, German Soc Clin Soc, Austrian Soc Clin Chem DE hair; mechanisms; drug binding; sweat; sebum; lipids; keratin; melanin; bias ID TESTING HUMAN HAIR; DECONTAMINATION PROCEDURES; COCAINE; ABUSE; CONTAMINATION; ACCUMULATION; METABOLITES AB Hair testing for drugs of abuse is a developing technology that offers the possibility of longer detection times than is commonly obtained with urine or blood analysis. There are many uncertainties concerning how drugs enter hair and factors that affect drug deposition and residence in hair. Possible routes of drug entry include diffusion from blood, sweat, sebum, and skin and entry from the environment. Evidence is reviewed regarding the importance of each of these routes as possible contributors to drug deposition in hair. Binding to specific sites in hair may involve both electrostatic forces and weaker attractions, such as van der Waals forces. Melanin and protein constituents of hair may serve as binding sites. Recent in vitro studies suggest that the color of hair or melanin content may be the major determinant of cocaine binding and, consequently, may result in color or ethnic bias in hair testing. RP Cone, EJ (reprint author), NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,NIH,POB 5180,BALTIMORE,MD 21224, USA. NR 27 TC 75 Z9 81 U1 4 U2 34 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD AUG PY 1996 VL 18 IS 4 BP 438 EP 443 DI 10.1097/00007691-199608000-00022 PG 6 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA UZ196 UT WOS:A1996UZ19600022 PM 8857565 ER PT J AU Huestis, MA AF Huestis, MA TI Judicial acceptance of hair tests for substances of abuse in the United States courts: Scientific, forensic, and ethical aspects SO THERAPEUTIC DRUG MONITORING LA English DT Article; Proceedings Paper CT 4th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology CY SEP 04-08, 1995 CL VIENNA, AUSTRIA SP Int Assoc Therapeut Drug Monitoring & Clin Toxicol, German Soc Clin Soc, Austrian Soc Clin Chem DE hair tests; judicial acceptance; drugs in hair AB Changes in the acceptance of hair test results in the United States courts have resulted from two factors: the rapidly evolving scientific understanding of hair test data; and modification of the admissibility standards for forensic evidence in United States courts. The scientific, forensic, and ethical aspects of drug testing in hair impact the acceptance of hair test results. Our knowledge and experience with this new analytical technology have been developing rapidly, although there are many unanswered questions that influence acceptance of data. A consequence of the recent U.S. Supreme Court decision to have the Federal Rules of Evidence take precedence over the Frye standard in the admissibility of scientific evidence has enabled judges to determine if evidence will assist in obtaining a fuller understanding of a given case. A summation of the scientific, forensic, and ethical aspects of judicial acceptance of hair test results may be: If hair test results are positive, have we proven beyond a reasonable doubt and/or demonstrated that the preponderance of evidence supports a finding of drug use? In general, recent court decisions indicate that hair test results provide information that the courts should consider. However, unresolved scientific, forensic, and ethical issues may have a greater effect on the weight applied to hair test evidence rather than its admissibility in future court proceedings. RP Huestis, MA (reprint author), NIDA,LAB CHEM & DRUG METAB,ADDICT RES CTR,NIH,4940 EASTERN AVE,BLDG C,BALTIMORE,MD 21224, USA. NR 1 TC 18 Z9 18 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD AUG PY 1996 VL 18 IS 4 BP 456 EP 459 DI 10.1097/00007691-199608000-00025 PG 4 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA UZ196 UT WOS:A1996UZ19600025 PM 8857568 ER PT J AU Rouault, T Klausner, R AF Rouault, T Klausner, R TI Iron-sulfur clusters and oxidant stress responses - Reply SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter RP Rouault, T (reprint author), NICHHD,CELL BIOL & METAB BRANCH,SECT HUMAN IRON METAB,BLDG 18,ROOM 101,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1996 VL 21 IS 8 BP 283 EP 283 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB985 UT WOS:A1996VB98500003 ER PT J AU Landsman, D AF Landsman, D TI Histone H1 in Saccharomyces cerevisiae: A double mystery solved? SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID CHROMATIN STRUCTURE; TOOL; DNA RP NIH, NATL CTR BIOTECHNOL INFORMAT, NATL LIB MED, BLDG 38A, ROOM 8N-807, BETHESDA, MD 20894 USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 15 TC 55 Z9 56 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1996 VL 21 IS 8 BP 287 EP 288 DI 10.1016/S0968-0004(96)30030-3 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB985 UT WOS:A1996VB98500006 PM 8772381 ER PT J AU Werner, MH Huth, JR Gronenborn, AM Clore, GM AF Werner, MH Huth, JR Gronenborn, AM Clore, GM TI Molecular determinants of mammalian sex SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID SRY-RELATED GENE; INHIBITING SUBSTANCE GENE; MULLERIAN DUCT SYNDROME; STEROIDOGENIC FACTOR-I; DNA-BINDING; HMG BOX; CAMPOMELIC DYSPLASIA; WILMS-TUMOR; XY FEMALES; MUTATIONS AB Mammalian male sex determination is controlled by a complex hierarchy. of gene regulatory proteins and hormones, which promote male gonadal development and regression of the female primordia. At the core of this pathway lies the SRY protein, the master developmental switch for testicular differentiation and hence, the male sex, The three-dimensional structure of the SRY-DNA complex suggests a model of developmental gene regulation in which proteins that alter DNA structure and promote the assembly of higher-order nucleoprotein complexes play an essential role in the timing of cell specialization events. RP Werner, MH (reprint author), NIDDK,NIH,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 49 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1996 VL 21 IS 8 BP 302 EP 308 DI 10.1016/0968-0004(96)10032-3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB985 UT WOS:A1996VB98500009 PM 8772384 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Is your fluorometer on the blink? SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1996 VL 21 IS 8 BP 317 EP 318 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VB985 UT WOS:A1996VB98500013 PM 8772388 ER PT J AU Benton, D AF Benton, D TI Bioinformatics - Principles and potential of a new multidisciplinary tool SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID MULTIPLE SEQUENCE ALIGNMENT; DATA-BANK; STRUCTURE PREDICTION; HUMAN GENOME; DATABASES; CRYSTALLOGRAPHY; INFORMATION; LIBRARIES; FEATURES; PROTEINS AB The materials of bioinformatics are biological data, and its methods are derived from a wide variety of computational techniques. Recent years have seen an explosive growth in biological data, and the development of novel computational methods. These methods have become essential to research progress in structural biology, genomics, structure-based drug design and molecular evolution. The development and maintenance of a robust infrastructure of biological data is of equal importance if biotechnology is to take maximum advantage of research advances in a wide variety of fields. While bioinformatics has already made important contributions, it faces significant challenges as it matures. RP Benton, D (reprint author), NATL INST HLTH,NATL CTR HUMAN GENOME RES,38 LIB DR,BETHESDA,MD 20892, USA. NR 116 TC 41 Z9 51 U1 1 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD AUG PY 1996 VL 14 IS 8 BP 261 EP 272 DI 10.1016/0167-7799(96)10037-8 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VC203 UT WOS:A1996VC20300001 PM 8987456 ER PT J AU Mushegian, AR Koonin, EV AF Mushegian, AR Koonin, EV TI Gene order is not conserved in bacterial evolution SO TRENDS IN GENETICS LA English DT Letter ID PROTEINS RP Mushegian, AR (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. OI Mushegian, Arcady/0000-0002-6809-9225 NR 11 TC 133 Z9 136 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD AUG PY 1996 VL 12 IS 8 BP 289 EP 290 DI 10.1016/0168-9525(96)20006-X PG 2 WC Genetics & Heredity SC Genetics & Heredity GA VA713 UT WOS:A1996VA71300005 PM 8783936 ER PT J AU Kuzio, J AF Kuzio, J TI Genomic sequence presentation SO TRENDS IN GENETICS LA English DT Article ID MAP RP Kuzio, J (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD AUG PY 1996 VL 12 IS 8 BP 321 EP 322 DI 10.1016/0168-9525(96)60032-8 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA VA713 UT WOS:A1996VA71300012 PM 8783943 ER PT J AU Steinhauser, C Gallo, V AF Steinhauser, C Gallo, V TI News on glutamate receptors in glial cells SO TRENDS IN NEUROSCIENCES LA English DT Article ID EXCITATORY AMINO-ACIDS; RAT OPTIC-NERVE; KAINATE RECEPTORS; OLIGODENDROCYTE DEVELOPMENT; CA2+ PERMEABILITY; CORPUS-CALLOSUM; PRECURSOR CELLS; MESSENGER-RNAS; NMDA RECEPTOR; IN-SITU AB Glutamate (Glu) receptors convey most of the excitatory synaptic transmission in the mammalian CNS. Distinct Glu-receptor genes and different subtypes of glutamate-activated channels are expressed ubiquitously throughout the developing and mature brain in the two major macroglial cell types, astrocytes and oligodendrocytes. These glial receptors are found in acutely isolated cells and in brain slices, and are therefore functional in vivo. Glutamate receptors in glial cells are activated during neuronal activity, and their activation modulates gene expression in astrocytes and oligodendrocytes. The proliferation and differentiation of glial precursor cells are also regulated by activation of Glu receptors, suggesting that the excitatory transmitter might be one of the environmental signals that regulate glial-cell development. C1 NICHHD,NIH,LAB CELLULAR & MOL NEUROPHYSIOL,BETHESDA,MD 20892. RP Steinhauser, C (reprint author), UNIV JENA,INST PHYSIOL,ABT NEUORPHYSIOL,TEICHGRABEN 8,D-07740 JENA,GERMANY. NR 99 TC 277 Z9 292 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD AUG PY 1996 VL 19 IS 8 BP 339 EP 345 DI 10.1016/0166-2236(96)10043-6 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VA750 UT WOS:A1996VA75000007 PM 8843603 ER PT J AU Kostenis, E Mohr, K AF Kostenis, E Mohr, K TI Two-point kinetic experiments to quantify allosteric effects on radioligand dissociation SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; HEPTANE-1,7-BIS(DIMETHYL-3'-PHTHALIMIDOPROPYL)AMMONIUM BROMIDE; ANTAGONIST BINDING; M1; GALLAMINE; MODULATION; LIGANDS; AGENTS; SITES; M2 AB Allosteric modulation of a receptor may be proved experimentally by demonstrating an altered radioligand dissociation in the presence of the allosteric modulator. Two-point kinetic experiments provide a screening-type approach to determine the delay of radioligand dissociation caused by allosteric modulation. In this article, Evi Kostenis and Klaus Mohr describe a pitfall in the data analysis that may lead to a suboptimum determination of the allosteric potency in the case of monophasic dissociations, and suggest how this problem may be resolved. C1 UNIV BONN,INST PHARM,DEPT PHARMACOL & TOXICOL,D-53121 BONN,GERMANY. RP Kostenis, E (reprint author), NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 22 TC 74 Z9 74 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD AUG PY 1996 VL 17 IS 8 BP 280 EP 283 DI 10.1016/0165-6147(96)10034-1 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VE082 UT WOS:A1996VE08200003 PM 8810873 ER PT J AU RamseyEwing, AL Moss, B AF RamseyEwing, AL Moss, B TI Complementation of a vaccinia virus host-range K1L gene deletion by the nonhomologous CP77 gene SO VIROLOGY LA English DT Article ID HAMSTER OVARY CELLS; WHITE POCK MUTANTS; INTERMEDIATE-STAGE GENES; OPEN READING FRAME; PROTEIN-SYNTHESIS; RABBITPOX VIRUS; ECTROMELIA VIRUS; MESSENGER-RNAS; HR MUTANTS; SEQUENCE AB We investigated the host-range restriction of a vaccinia virus (VV) K1L deletion mutant in rabbit kidney RK13 cells and the ability of the nonhomologous cowpox virus CP77 gene to overcome this block. Viral early mRNAs were made by K1L(-) VV but early protein synthesis was arrested consistent with a translational block. Replication of viral DNA did not occur and neither intermediate nor late mRNAs or proteins were detected. These results indicated that host-range restriction occurs earlier in RK13 cells than in Chinese hamster ovary cells (CHO) cells infected with CP77(-) VV, where the block occurs at translation of intermediate stage mRNA. We confirmed a report (Perkus et al., Virology 179, 276-286, 1990) that the CP77 gene, which allows VV replication in CHO cells, could replace the K1L gene for plaque formation in RK13 cells. However, the size of the plaques formed by K1L(-)CP77(+) VV was smaller than those formed by K1L(+)CP77(-) VV. Single-step growth curves also showed that the CP77 gene could functionally replace the K1L gene, although formation of infectious virus was delayed and did not reach the same level as that of K1L(+) VV. Most surprisingly, the dramatic shutoff of viral and host gene expression was similar in RK13 cells infected with K1L(-)CP77(-) VV and K1L(-)CP77(+) VV and little difference was noted for the first 6 hr. Subsequently, in cells infected with the K1L(-)CP77(+) VV, viral early protein synthesis was spontaneously resurrected and the replication cycle proceeded. Despite the absence of homology, K1L and CP77 gene products appear to be acting in a common virus/cell interaction pathway. (C) 1996 Academic Press, Inc. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 40 TC 36 Z9 38 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 1996 VL 222 IS 1 BP 75 EP 86 DI 10.1006/viro.1996.0399 PG 12 WC Virology SC Virology GA VB377 UT WOS:A1996VB37700008 PM 8806489 ER PT J AU Nekhai, S Kumar, A Bottaro, DP Petryshyn, R AF Nekhai, S Kumar, A Bottaro, DP Petryshyn, R TI Peptides derived from the interferon-induced PKR prevent activation by HIV-1 TAR RNA SO VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; DEPENDENT PROTEIN-KINASE; HUMAN IMMUNODEFICIENCY VIRUS-1; ADENOVIRUS VAI RNA; NF-KAPPA-B; BINDING DOMAIN; MESSENGER-RNA; HELIX FORMATION; P68 KINASE; MECHANISM AB The double-stranded RNA-dependent protein kinase (PKR) is believed to mediate cellular antiviral responses, function as a tumor suppressor, and regulate cell growth and differentiation. Its activation is dependent on double-stranded RNA (dsRNA) structures but these interactions are not fully understood. The possibility of direct interaction between dsRNA and the arginine and lysine-rich region of PKR (residues 54-74) was examined using synthetic peptides. We found that addition of a synthetic peptide corresponding to residues 54-74 of murine PKR or residues 60-80 of human PKR inhibited the autophosphorylation and activation of the kinase by either poly(l)-poly(C) or the 82-nucleotide-long TAR RNA. Gel-shift analysis indicated that the peptides disrupted the kinase-TAR complex by binding directly to TAR RNA. These findings delineate at least one dsRNA-binding domain in PKR which may be important for its cellular activation. (C) 1996 Academic Press, Inc. C1 CHILDRENS NATL MED CTR,CTR CANC & TRANSPLANTAT BIOL,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,SCH MED,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20010. NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU NCI NIH HHS [CA42717]; PHS HHS [A125531] NR 58 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 1996 VL 222 IS 1 BP 193 EP 200 DI 10.1006/viro.1996.0410 PG 8 WC Virology SC Virology GA VB377 UT WOS:A1996VB37700019 PM 8806499 ER PT J AU Brother, MB Chang, HK Lisziewicz, J Su, D Murty, LC Ensoli, B AF Brother, MB Chang, HK Lisziewicz, J Su, D Murty, LC Ensoli, B TI Block of Tat-mediated transactivation of tumor necrosis factor beta gene expression by polymeric-TAR decoys SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; IMMUNE-DEFICIENCY SYNDROME; TRANS-ACTIVATION REQUIRES; INFECTED T-CELLS; KAPOSIS-SARCOMA; HIV-1 TAT; MESSENGER-RNA; AIDS PATIENTS; GROWTH-FACTOR AB The tat gene product (Tat) of human immunodeficiency virus type 1 (HIV-1) is an early regulatory protein which transactivates HIV-I gene expression by interacting with the trans-activation response element (TAR) present in the HIV-1 long terminal repeat (LTR). In HIV-1-infected cells Tat can also activate the expression of tumor necrosis factor (TNF). Recent results indicate that essential for this effect is the interaction of Tat with a TAR-like structure present in the TNF beta messenger RNA leader region that closely resembles the TAR of the HIV-LTR. Here we show that because of this similarity of mechanisms, the expression of an RNA species encoding polymeric-TAR sequences and known to inhibit Tat-mediated HIV-1 gene expression also blocks TNF gene expression in response to Tat, but not TNF promoter activation induced by human T cell leukemia/lymphotropic virus type I Tax protein. Since TNF is increased in HIV-1-infected individuals and can activate HIV-1 gene expression or rescue Tat-defective HIV-1 proviruses, activation of TNF by Tat may be part of a complex pathway in which HIV-1 uses its own expression to increase infectivity and to induce disease. This study shows a dual role for the polymeric-TAR construct in inhibiting HIV-1 replication and strengthens the potential use of this protective gene in gene therapy for AIDS. (C) 1996 Academic Press, Inc. C1 UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA 98195. NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 50 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 1996 VL 222 IS 1 BP 252 EP 256 DI 10.1006/viro.1996.0416 PG 5 WC Virology SC Virology GA VB377 UT WOS:A1996VB37700025 PM 8806505 ER PT J AU Leibenluft, E Albert, PS Rosenthal, NE Wehr, TA AF Leibenluft, E Albert, PS Rosenthal, NE Wehr, TA TI Relationship between sleep and mood in patients with rapid-cycling bipolar disorder SO PSYCHIATRY RESEARCH LA English DT Article DE circadian rhythms; hypomania; mania; depression; wake onset ID CIRCADIAN-RHYTHM; DEPRESSION AB The relationship between sleep and mood was examined in a longitudinal, naturalistic data set derived from out-patients with rapid-cycling bipolar disorder. Eleven patients completed daily self-ratings of mood and sleep logs for 18 months. Using logistic regression with autoregressive terms, we examined the effect of prior sleep (sleep duration, time of sleep onset, and time of wake onset) on the probability of being in a depressed, manic, or hypomanic episode on one or more subsequent days. Of the three sleep parameters, decreased sleep duration was the best predictor of mania or hypomania the next day, followed by wake onset time. The association between sleep duration and subsequent mood was less consistent for depression than for mania or hypomania. Four of the patients showed no relationship between mood and any of the sleep variables measured. These results reinforce the importance of monitoring, and perhaps controlling, sleep duration and wake onset time in at least some patients with rapid-cycling bipolar disorder. C1 NHLBI,OFF BIOSTAT RES,BETHESDA,MD 20892. RP Leibenluft, E (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,10-4S-239,10 CTR DR,MSC 1390,BETHESDA,MD 20892, USA. NR 22 TC 93 Z9 93 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 31 PY 1996 VL 63 IS 2-3 BP 161 EP 168 DI 10.1016/0165-1781(96)02854-5 PG 8 WC Psychiatry SC Psychiatry GA VF721 UT WOS:A1996VF72100007 PM 8878312 ER PT J AU Park, C Chamberlin, ME Pan, CJ Chou, JY AF Park, C Chamberlin, ME Pan, CJ Chou, JY TI Differential expression and butyrate response of human alkaline phosphatase genes are mediated by upstream DNA elements SO BIOCHEMISTRY LA English DT Article ID HUMAN CHORIOCARCINOMA CELLS; SODIUM-BUTYRATE; TRANSCRIPTIONAL ACTIVATION; BINDING; GLYCOSYLATION; TRANSFECTION; COACTIVATORS; EFFICIENCY; SEQUENCE; SEMINOMA AB Human placentas express high levels of the placental alkaline phosphatase (FLAP) gene and low levels of a highly related gene, germ cell AP (GCAP). Malignant transformation of the placenta is accompanied by a reversal of this pattern of expression. Three Spl-binding GC-rich DNA elements (sites I-III) located within the first 156 base pairs upstream of the GCAP gene have been shown to direct optimal GCAP gene expression in choriocarcinoma cells. Here we show that the first 100 base pairs upstream of the GCAP gene, which contains sites I and II, constitutes a minimal GCAP promoter. The simultaneous presence of both sites I and II is necessary for GCAP expression and its induction by sodium butyrate. The FLAP promoter directs only a very low level of gene expression in choriocarcinoma cells; the expression does not respond to butyrate. The -100/-1 DNA regions between the GCAP and FLAP promoters differ by only eight base pairs. However, the GC-rich stretches in sites I and II of the GCAP promoter are disrupted in the corresponding FLAP promoter. This disruption blocks or markedly reduces the binding of choriocarcinoma nuclear factors to the FLAP promoter, leading to a reduction in expression and a loss of butyrate response. We further demonstrate that nucleotides -75 to -58 in both AP promoters, which bind a human Y-box binding protein, appear to down-regulate GCAP expression. C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NR 31 TC 11 Z9 11 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 30 PY 1996 VL 35 IS 30 BP 9807 EP 9814 DI 10.1021/bi9602223 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VA025 UT WOS:A1996VA02500021 PM 8703954 ER PT J AU Romanova, LY Alexandrov, IA Schwab, G Hilbert, DM Mushinski, JF Nordan, RP AF Romanova, LY Alexandrov, IA Schwab, G Hilbert, DM Mushinski, JF Nordan, RP TI Mechanism of apoptosis suppression by phorbol ester in IL-6-starved murine plasmacytomas: Role of PKC modulation and cell cycle SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; MYC-INDUCED APOPTOSIS; DNA FRAGMENTATION; LYMPHOMA CELLS; LEUKEMIA-CELLS; DEATH; FIBROBLASTS; INDUCTION; PHOSPHORYLATION; ACTIVATION AB We show here that the mode of cell death in IL-6-starved T1165 and T1198 plasmacytoma cell lines is apoptosis, and that it can be suppressed by phorbol ester (PMA) treatment in a protein kinase C (PKC)-mediated process that involves alpha and/or delta isozymes. PMA-induced PKC activation, but not the depletion that follows it, participates in the suppression of apoptosis. Extended PKC activation is necessary but not sufficient for the apoptosis suppression. In addition, the cells must be in a ''competent'' state, which appears not to be determined by PKC. We observed two points of ''competence'' during the time between withdrawal of IL-6 and the start of massive cell death: one, immediately after withdrawal, and another, just before onset of apoptosis, at the time corresponding to maximal accumulation of cells in a G0/G1 black imposed by IL-6 withdrawal, Treatment with PMA and other PKC activators resulted in a shift of the cell population to S phase, Lifting the G0/G1 block, We propose a model in which cells are rescued in a certain stage of the G1 phase of cell cycle. Death suppression occurs when a transient PMA-induced PKC activation occurs when a significant number of cells are in this part of G1. allowing them to pass the restriction point safely without initiating the cell death program. C1 US FDA, CTR BIOL EVALUAT & RES, DIV MONOCLONAL ANTIBODIES, BETHESDA, MD 20892 USA. NCI, GENET LAB, NIH, BETHESDA, MD 20892 USA. NR 32 TC 32 Z9 32 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 30 PY 1996 VL 35 IS 30 BP 9900 EP 9906 DI 10.1021/bi9525886 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VA025 UT WOS:A1996VA02500031 PM 8703964 ER PT J AU Yu, KF AF Yu, KF TI Estimation of a common odds ratio under binary cluster sampling SO STATISTICS IN MEDICINE LA English DT Letter RP Yu, KF (reprint author), NICHHD,BMSB,DESPR,NIH,BLDG 6100,ROOM 7B13,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 30 PY 1996 VL 15 IS 14 BP 1595 EP 1599 PG 5 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UZ622 UT WOS:A1996UZ62200013 PM 8855486 ER PT J AU Contrera, J AF Contrera, J TI More on David Baltimore SO CHEMICAL & ENGINEERING NEWS LA English DT Letter RP Contrera, J (reprint author), NIH,OFF TECHNOL TRANSFER,ROCKVILLE,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0009-2347 J9 CHEM ENG NEWS JI Chem. Eng. News PD JUL 29 PY 1996 VL 74 IS 31 BP 61 EP 62 PG 2 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA UZ349 UT WOS:A1996UZ34900024 ER PT J AU Zimmerman, SB Murphy, LD AF Zimmerman, SB Murphy, LD TI Macromolecular crowding and the mandatory condensation of DNA in bacteria SO FEBS LETTERS LA English DT Article DE cytoplasmic macromolecule; DNA condensation; Escherichia coli; macromolecular crowding; mandatory condensation; nucleoid ID INDUCE NUCLEAR DISRUPTION; ESCHERICHIA-COLI; BACTERIOPHAGE-T4 DEFICIENT; LIGHT-MICROSCOPY; PHASE-CONTRAST; MUTANTS; ABILITY; HOST; POLYAMINES; POLYMERASE AB Cellular DNA in bacteria is localized into nucleoids enclosed by cytoplasm, The forces which cause condensation of the DNA into nucleoids are poorly understood, We suggest that direct and indirect macromolecular crowding forces from the surrounding cytoplasm are critical factors for nucleoid condensation, and that within a bacterial cell these crowding forces are always present at such high levels that the DNA is maintained in a condensed state, The DNA affected includes not only the preexisting genomic DNA but also DNA that is newly introduced by viral infection, replication or other means. RP Zimmerman, SB (reprint author), NIDDKD,MOL BIOL LAB,NIH,BLDG 5,ROOM 328W,BETHESDA,MD 20892, USA. NR 49 TC 100 Z9 102 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 29 PY 1996 VL 390 IS 3 BP 245 EP 248 DI 10.1016/0014-5793(96)00725-9 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VA112 UT WOS:A1996VA11200001 PM 8706869 ER PT J AU Persson, I Yuen, J Bergkvist, L Schairer, C AF Persson, I Yuen, J Bergkvist, L Schairer, C TI Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy - Long-term follow-up of a Swedish cohort SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BREAST-CANCER; ENDOMETRIAL CANCER; POSTMENOPAUSAL WOMEN; EXOGENOUS HORMONES; COLON-CANCER; RISK; POPULATION; LIFE AB We analyzed cancer incidence and mortality in a cohort of 22,597 Swedish women who were prescribed replacement hormones. After 13 years of follow-up in national registries, 2,330 incident cancer cases and 848 cancer deaths were observed. Overall, our results were reassuring since incidence rate ratios (SIRs) for 16 cancer sites and mortality ratios (SMRs) for all 10 examined sites were at, or lower than, unity. However, we found that exposure to an estrogen-progestin combined brand was associated with an increasing relative risk of breast cancer with follow-up time, the SIR reaching 1.4 (95% CI 1.1-1.8) after 10 years of follow-up. The relative risk of endometrial cancer was substantially increased, with the highest SIR of 5.0 (95% CI 1.6-5.9) in women prescribed estrogens alone, whereas those given an estrogen-progestin combination showed no elevation in risk. The risk estimates for liver and biliary tract cancers and for colon cancer were reduced by about 40%, notably in women prescribed the estradiol-progestin compound. Further detailed analyses revealed no evidence of adverse or protective effects on the risk of ovarian, uterine cervical, vulvar/vaginal, rectal, pancreatic, renal, lung, thyroid and other endocrine cancers, brain tumors, malignant melanoma or other skin cancers. Hormone replacement therapy was not associated with an increase in mortality for any cancer site, at this time of follow-up. For breast and endometrial cancers, SMRs were below baseline but tended to increase with follow-up time. We conclude that hormone replacement increases the endometrial-cancer risk after unopposed estrogens and the breast-cancer risk-notably after estrogen-progestin combined therapy-and tentatively suggest that it exerts a protective effect against colon and liver cancer risks. (C) 1996 Wiley-Liss, Inc. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,ROCKVILLE,MD. RP Persson, I (reprint author), UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. NR 30 TC 252 Z9 255 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 29 PY 1996 VL 67 IS 3 BP 327 EP 332 DI 10.1002/(SICI)1097-0215(19960729)67:3<327::AID-IJC4>3.0.CO;2-T PG 6 WC Oncology SC Oncology GA UZ986 UT WOS:A1996UZ98600004 PM 8707404 ER PT J AU Kolb, H Nelson, R AF Kolb, H Nelson, R TI Hyperpolarizing, small-field, amacrine cells in cone pathways of cat retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE electron microscopy; synaptic connections; intracellular recordings; HRP staining ID INNER PLEXIFORM LAYER; BETA-GANGLION-CELLS; RHESUS-MONKEY RETINA; RABBIT RETINA; MAMMALIAN RETINA; ELECTRON-MICROSCOPY; BIPOLAR CELLS; ROD PATHWAY; DOPAMINERGIC MODULATION; FUNCTIONAL ARCHITECTURE AB Intracellular recording and horseradish peroxidase (HRP) staining of amacrine cells in the isolated arterially perfused cat retina have revealed examples of small-field cells that hyperpolarize to light. Two were examined in detailed electron microscopic reconstructions to determine patterns of synaptic relationships within the inner plexiform layer (IPL). The cells were morphologically similar to A8 and A13 types as described in Golgi-impregnated material (Kolb et al. [1981] Vision Res. 21:1081-1114). Both types received ribbon synaptic input from rod and cone bipolar cells. The latter input was numerically predominant, occurred in both a and b sublaminae of the IPL, and arose from at least three cone bipolar types. Reciprocal synapses were evident between A13 cells and cone bipolar cells. Amacrine input occurred throughout the dendritic tree of both A8 and A13 types, and numerically exceeded bipolar cell input fbr A13. Gap junctions between stained, and similar-appearing unstained dendritic profiles were observed for both amacrine types. In addition, A8 engaged in gap junctions with cone bipolar profiles in sublamina b which also provided ribbon input. Synaptic output for both amacrine types occurred primarily upon amacrine and ganglion cells in sublamina a. Both cells were presynaptic upon single OFF-center beta ganglion cells running through the middle of their dendritic trees. Mixtures of rod and cone signals were found in the centrally evoked hyperpolarizations of each type. Center mechanism space constants of such types ranged from 100 to 400 mu m, with antagonistic surround in 1 of 5 cases. Dopamine (250 mu M) reduced receptive field space constants by one-third in one case. The synaptic organization and potential circuitry implications of these cone system-dominated amacrine types are compared and contrasted to the better-known AII and A17 types previously described for the rod system. (C) 1996 Wiley-Liss, Inc. C1 NINCDS,NEUROPHYSIOL LAB,NIH,BETHESDA,MD 20892. RP Kolb, H (reprint author), UNIV UTAH,HLTH SCI CTR,JOHN MORAN EYE CTR,SCH MED,50 N MED DR,SALT LAKE CITY,UT 84132, USA. FU NEI NIH HHS [EY 03323] NR 81 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 29 PY 1996 VL 371 IS 3 BP 415 EP 436 PG 22 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA UZ738 UT WOS:A1996UZ73800005 PM 8842896 ER PT J AU Feinberg, MB AF Feinberg, MB TI Changing the natural history of HIV disease SO LANCET LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLINICAL COURSE; INFECTION; PROGRESSION; DEFECTS; PLASMA; AIDS; PCR AB Our understanding of the pathogenesis of AIDS has advanced considerably since the disease was first reported 15 years ago. We now know that the primary damage inflicted by HIV-1 is mainly brought about by active virus replication. With the advent of sensitive tools for monitoring HIV replication in vivo, an individual's risk of disease progression can be assessed early in the course of the infection and the efficacy of antiviral therapies can now be determined accurately and expeditiously. When used appropriately, potent combinations of antiviral drugs seem to be able to circumvent the inherent tendency of HIV-1 to generate drug-resistant viruses, the main reason for failure of all antiviral therapies, and are significantly more effective than earlier approaches. For the first time, rational approaches to contain and perhaps eliminate HIV-1 infection can be pursued. RP Feinberg, MB (reprint author), NIH,OFF AIDS RES,BLDG 31,ROOM 4C06,31 CTR DR,BETHESDA,MD 20892, USA. NR 48 TC 94 Z9 95 U1 0 U2 6 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 27 PY 1996 VL 348 IS 9022 BP 239 EP 246 DI 10.1016/S0140-6736(96)06231-9 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UZ286 UT WOS:A1996UZ28600014 PM 8684203 ER PT J AU Ricketts, MH Goldman, D Long, JC Manowitz, P AF Ricketts, MH Goldman, D Long, JC Manowitz, P TI Arylsulfatase a pseudodeficiency-associated mutations: Population studies and identification of a novel haplotype SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE sulfatide; metachromatic leukodystrophy; polymorphism; haplotype ID DOPAMINE RECEPTOR GENOTYPE; METACHROMATIC LEUKODYSTROPHY; A PSEUDODEFICIENCY; MOLECULAR-GENETICS; DEFICIENCY; FREQUENCY; DIAGNOSIS; ALLELE; DISEASE AB Pseudodeficiency of arylsulfatase A is characterized by reduction of arylsulfatase A activity without neurodegeneration, making it an important complication when diagnosing metachromatic leukodystrophy, Two DNA substitutions are associated with arylsulfatase A pseudodeficiency. One, 1788A-->G, results in the loss of an N-glycosylated asparagine in the protein, and the second, 2723A-->G, removes the polyadenylation signal site of the mRNA, Previously, the polyadenylation signal site variant was observed only in the presence of the N-glycosylation site variant, although the latter has been reported to occur in the absence of the polyadenylation signal site variant, We investigated the frequencies of these alleles and their linkage disequilibrium in a number of populations and in psychiatric patients, While the N-glycosylation site variant had a high frequency in the Bantu-speaking people from Southern Africa (0.44), the San of Southern Africa (0.22), African Americans (0.37), and Cheyenne Indians (0.375), the polyadenylation signal site variant was absent in these groups, The mutated polyadenylation signal site was found only in the Caucasian groups surveyed. Two Caucasian sibs were identified with the pseudodeficiency polyadenylation signal site variant in the absence of the N-glycosylation site variant, indicating that linkage disequilibrium between the two polymorphisms is not perfect. (C) 1996 Wiley-Liss, Inc. C1 NIAAA,NEUROGENET LAB,BETHESDA,MD 20205. RP Ricketts, MH (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT PSYCHIAT,675 HOES LANE,PISCATAWAY,NJ 08854, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIAAA NIH HHS [R01-AA-07799] NR 30 TC 15 Z9 16 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 26 PY 1996 VL 67 IS 4 BP 387 EP 392 DI 10.1002/(SICI)1096-8628(19960726)67:4<387::AID-AJMG12>3.0.CO;2-F PG 6 WC Genetics & Heredity SC Genetics & Heredity GA UZ070 UT WOS:A1996UZ07000012 PM 8837707 ER PT J AU Altemus, M Murphy, DL Greenberg, B Lesch, KP AF Altemus, M Murphy, DL Greenberg, B Lesch, KP TI Intact coding region of the serotonin transporter gene in obsessive-compulsive disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE serotonin transporter; platelets obsessive-compulsive disorder ID IMIPRAMINE BINDING; EXPRESSION; PLATELETS; MUTATIONS; RECEPTOR; SITE; RNA AB Epidemiologic studies indicate that obsessivecompulsive disorder is genetically transmitted in some families, although no genetic abnormalities have been identified in individuals with this disorder. The selective response of obsessive-compulsive disorder to treatment with agents which block serotonin reuptake suggests the gene coding for the serotonin transporter as a candidate gene. The primary structure of the serotonin-transporter coding region was sequenced in 22 patients with obsessive-compulsive disorder, using direct PCR sequencing of cDNA synthesized from platelet serotonin-transporter mRNA, No variations in aminoacid sequence were found among the obsessive-compulsive disorder patients or healthy controls, These results do not support a role for alteration in the primary structure of the coding region of the serotonin-transporter gene in the pathogenesis of obsessive-compulsive disorder. (C) 1996 Wiley-Liss, Inc. C1 UNIV WURZBURG,DEPT PSYCHIAT,D-8700 WURZBURG,GERMANY. RP Altemus, M (reprint author), NIMH,CLIN SCI LAB,NIH,DIRP BLDG 10,ROOM 3D41,10 CTR DR,MSC 1264,BETHESDA,MD 20892, USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 27 TC 38 Z9 39 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 26 PY 1996 VL 67 IS 4 BP 409 EP 411 DI 10.1002/(SICI)1096-8628(19960726)67:4<409::AID-AJMG16>3.0.CO;2-N PG 3 WC Genetics & Heredity SC Genetics & Heredity GA UZ070 UT WOS:A1996UZ07000016 PM 8837711 ER PT J AU Whalen, R Kempner, ES Boyer, TD AF Whalen, R Kempner, ES Boyer, TD TI Structural studies of a human pi class glutathione S-transferase - Photoaffinity labeling of the active site and target size analysis SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE glutathione transferases; human; active site; affinity labels; protein structure; radiation effects ID SUBSTRATE-BINDING-SITE; 3-DIMENSIONAL STRUCTURE; RADIATION INACTIVATION; POLYACRYLAMIDE GELS; CATALYTIC ACTIVITY; ISOENZYME 3-3; PROTEINS; LIVER; S-(4-BROMO-2,3-DIOXOBUTYL)GLUTATHIONE; RESOLUTION AB The glutathione S-transferases (GSTs; EC 2.5.1.18) are a family of dimeric proteins that catalyze reactions between glutathione (GSH) and various electrophiles. A partial cDNA for human GST pi was obtained and the open reading frame completed. The completed cDNA was cloned, and GST pi protein was expressed in bacteria. Cloned enzyme was purified and had the same kinetic constants, molecular mass, pI value, and N-terminal sequence as placental GST pi except that some of the polypeptides had N-terminal methionines. A radiolabeled azido derivative of GSH, S-(p-azidophenacyl)-[H-3]glutathione, was used to photoaffinity-label the active site of the cloned enzyme. Labeled enzyme did not bind to a GSH-agarose affinity column. Labeling was prevented in the presence of S-hexylglutathione, and noncovalently-bound azido affinity label was a competitive inhibitor towards 1-chloro-2,4-dinitrobenzene and GSH. These results suggest that the azido label was binding at the active site of the enzyme. Photoaffinity-labeled enzyme was trypsinized, and two labeled peptides were purified and sequenced. One peptide corresponded to residues 183-188, whereas the other corresponded to residues 183-186. These residues appear to form part of the hydrophobic (H-site) binding region of human GST pi that has not been shown previously. Cloned enzyme was subjected to radiation inactivation to assess the importance of subunit interactions in the maintenance of catalytic activity. The target size of enzymatic activity (23 kDa) was not significantly different from that of the protein monomer (24 kDa). Therefore, each subunit of human GST pi appears to be capable of independent catalytic activity. C1 EMORY UNIV,SCH MED,DIV DIGEST DIS,ATLANTA,GA 30322. NIAMSD,PHYS BIOL LAB,NIH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM-31555] NR 36 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 26 PY 1996 VL 52 IS 2 BP 281 EP 288 DI 10.1016/0006-2952(96)00205-5 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UU383 UT WOS:A1996UU38300013 PM 8694853 ER PT J AU Kawamoto, S AF Kawamoto, S TI Neuron-specific alternative splicing of nonmuscle myosin II heavy chain-B pre-mRNA requires a cis-acting intron sequence SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; GENE; EXON; MOLECULE; CLONING; ISOFORM; ELEMENT; REGION; CELLS; SITE AB In addition to the ubiquitously expressed form of nonmuscle myosin II heavy chain-B (MHC-B), the existence of a neuron-specific MHC-B isoform, which contains a 30-nucleotide inserted sequence near the ATP binding region, has been reported (Takahashi, M,, Kawamoto, S,, and Adelstein, R, S, (1992) J. Biol, Chem, 267, 17864-17871), In this study, the genomic location of the neuron-specific inserted 30-nucleotide sequence found in the cDNA is determined to be a single cassette type exon, N30, in the human nonmuscle MHC-B gene, Inclusion or exclusion of exon N30 is cell type-specific, with inclusion being restricted to neuronal cells and being regulated during cell differentiation. Expression of a minigene construct that contains the alternative exon N30 along with the flanking introns and exons was studied in human neuronal retinoblastoma Y79 cells, Inclusion of the N30 exon in the mRNA from the transfected minigene occurs in differentiated Y79 cells that have been treated with butyrate but not in the undifferentiated Y79 cells and non-neuronal cell lines, Systematic deletion and mutation analysis of the minigene construct established that neuron-specific N30 exon recognition requires a cis-acting RNA sequence located similar to 1.5 kilobases downstream of the N30 exon. RP Kawamoto, S (reprint author), NHLBI,NIH,MOLEC CARDIOL LAB,BLDG 10,RM 8N202,10 CTR DR,MSC 1762,BETHESDA,MD 20892, USA. NR 28 TC 66 Z9 66 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 26 PY 1996 VL 271 IS 30 BP 17613 EP 17616 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY935 UT WOS:A1996UY93500006 PM 8663598 ER PT J AU Lechleider, RJ deCaestecker, MP Dehejia, A Polymeropoulos, MH Roberts, AB AF Lechleider, RJ deCaestecker, MP Dehejia, A Polymeropoulos, MH Roberts, AB TI Serine phosphorylation, chromosomal localization, and transforming growth factor-beta signal transduction by human bsp-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA; EPITHELIAL-CELLS; RECEPTOR; GENE; ACTIVATION; DROSOPHILA; PATHWAYS; HOMOLOG; PATTERN AB The transforming growth factor-beta (TGF-beta) superfamily regulates a multitude of cellular and developmental events. TGF-beta family ligands signal through transmembrane serine/threonine kinase receptors whose downstream effecters are largely unknown, Using genetic data from the fruit fly, we have identified a downstream effector of TGF-beta-induced signaling. TGF-beta signaling protein-1 (BSP-1) is rapidly phosphorylated in response to TGF-beta. Localization of bsp-l to chromosome 4q28 suggests a role in carcinogenesis. These data suggest that BSP-1 is the prototype of a new class of signaling molecules. C1 NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,GENE MAPPING UNIT,BETHESDA,MD 20892. RP Lechleider, RJ (reprint author), NCI,CHEMOPREVENT LAB,NIH,41 LIB DR,BETHESDA,MD 20892, USA. NR 36 TC 71 Z9 72 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 26 PY 1996 VL 271 IS 30 BP 17617 EP 17620 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY935 UT WOS:A1996UY93500007 PM 8663601 ER PT J AU Robey, FA HarrisKelson, T RobertGuroff, M Batinic, D Ivanov, B Lewis, MS Roller, PP AF Robey, FA HarrisKelson, T RobertGuroff, M Batinic, D Ivanov, B Lewis, MS Roller, PP TI A synthetic conformational epitope from the C4 domain of HIV Gp120 that binds CD4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; AUTOMATED SYNTHESIS; MODIFIED PEPTIDES; T4 MOLECULE; RECEPTOR; TYPE-1; PROTEIN; INFECTION; SWITCH AB The fourth conserved domain of the human immunodeficiency virus type 1 (HIV-1) envelope, the C4 region of glycoprotein 120 (gp120), is believed to be a major part of gp120 that is necessary for binding to CD4, Recently, we found that C4 in gp120 is probably an alpha-helix, because antibodies made against helical constructs of C4 react with native and recombinant gp120 but antibodies against linear C4 constructs do not. For the present study, we performed experiments to determine, first, if CD4 could bind to the helical C4 constructs and, second, if the binding was comparable with CD4 binding to gp120. Immobilized helical constructs derived from the C4s from HTV-1 and HIV-2 bound biotinylated recombinant CD4 with K-d values of 8.59 nM and 14.59 nM, respectively. Recombinant soluble CD4 inhibited the binding of biotinylated CD4 to the C4 construct from HIV-1 with a K-d of 9.88 nM, and recombinant gp120 blocked the binding of CD4 to the immobilized helical construct from C4 of HIV-1 with a K-d of 8.08 nn. The C4 peptide-(419-436) from HIV-1 (KIKQIINMWQEVGKAMYA-NH2) blocked CD4 binding to gp120 but only in a buffer con containing 0.03% Brij 35 where the peptide displayed 17 +/- 1% alpha-helix; without the Brij 35, peptide-(419-436) displayed no helical content, The K-d for the peptide-(419-436) blocking CD4 binding to gp120 in Brij 35-containing buffer was found to be 42 mu M. These results indicate that C4 constructs from HTV-1 and HIV-2 do bind CD4, but the constructs must display an alpha-helical conformation to do so. In addition, the results reported here will provide answers to key questions about structural requirements for HIV vaccines and therapeutics that hinge on under standing the molecular nature of the gp120-CD4 interaction as the first step in the HIV infection process. C1 NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,NIH,BETHESDA,MD 20892. RP Robey, FA (reprint author), NIDR,PEPTIDE & IMMUNOCHEM UNIT,NIH,BLDG 30,RM 211,BETHESDA,MD 20892, USA. NR 35 TC 26 Z9 27 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 26 PY 1996 VL 271 IS 30 BP 17990 EP 17995 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY935 UT WOS:A1996UY93500063 PM 8663408 ER PT J AU Takagi, Y Nomizu, M Gullberg, D MacKrell, AJ Keene, DR Yamada, Y Fessler, JH AF Takagi, Y Nomizu, M Gullberg, D MacKrell, AJ Keene, DR Yamada, Y Fessler, JH TI Conserved neuron promoting activity in Drosophila and vertebrate laminin alpha 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; A-CHAIN; EXTRACELLULAR-MATRIX; ADHESION MOLECULE; SYNTHETIC PEPTIDE; NEURITE OUTGROWTH; GLOBULAR DOMAIN; HEPARIN-BINDING; CELL ATTACHMENT; IKVAV SEQUENCE AB Drosophila S2 cells were transfected with constructs that code for two portions of the Drosophila laminin cu chain. Construct rec alpha L coded for domains III, I/II, and G of laminin alpha., Construct rec alpha S coded for only the COOH- most 12% of the I/II domain and the G domain, The corresponding polypeptides were isolated and characterized from the culture media. The rec alpha L chain partly formed disulfide-linked heterotrimers with the endogenously produced beta and gamma laminin chains. Like normal Drosophila laminin, a substrate coating of either rec alpha L or rec alpha S supported neuron differentiation and neurite extension of primary Drosophila embryo cell cultures. However, at the same low concentrations, only Drosophila laminin-1, but neither rec alpha L nor rec alpha S supported myogenesis in these cultures. Previously, an overlapping set of dodecapeptides that covered a region of the murine laminin alpha 1 chain similar to rec alpha S had been synthesized and tested for cell culture support properties (Nomizu, M., Rim, W. H., Yamamura, K., Utani, A., Otaka, A., Roller, P. P., Kleinman, H. K., and Yamada, Y. (1995) J. Biol. Chem. 270, 20583-20590). The Drosophila laminin cu homologues of the six most active vertebrate dodecapeptides were now synthesized and tested as substrates for differentiation of primary Drosophila embryo cells. Peptides that contained either the Drosophila sequence SIKVGV or the murine homologue, SIKVAV, provided support for neurite extension. C1 UNIV CALIF LOS ANGELES,INST MOL BIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,DEPT BIOL,LOS ANGELES,CA 90095. SHRINERS HOSP CRIPPLED CHILDRENS,PORTLAND,OR 97201. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. RI Gullberg, Donald/H-2495-2016 OI Gullberg, Donald/0000-0002-7245-4437 FU NIA NIH HHS [AG02128] NR 60 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 26 PY 1996 VL 271 IS 30 BP 18074 EP 18081 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY935 UT WOS:A1996UY93500073 PM 8663504 ER PT J AU deMora, JF Guerrero, C Mahadevan, D Coque, JJR Rojas, JM Esteban, LM Rebecchi, M Santos, E AF deMora, JF Guerrero, C Mahadevan, D Coque, JJR Rojas, JM Esteban, LM Rebecchi, M Santos, E TI Isolated Sos1 PH domain exhibits germinal vesicle breakdown-inducing activity in Xenopus oocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLECKSTRIN-HOMOLOGY DOMAIN; X-LINKED AGAMMAGLOBULINEMIA; BRUTON TYROSINE KINASE; MEIOTIC MATURATION; ONCOGENE PRODUCT; PHOSPHATIDYLINOSITOL 3-KINASE; BETA-SPECTRIN; RAS PROTEINS; INSULIN; INDUCTION AB Purified, bacterially expressed PH domains of Sos1, IRS-1, beta ARK, and PLC delta(1) were analyzed functionally by means of microinjection into full grown, stage VI Xenopus laevis oocytes, Whereas the PH domains from IRS-1, beta ARK, or PLC delta(1) did not show any effect in the oocytes, injection of the purified Sos1 PH domain resulted in induction of significant rates of germinal vesicle breakdown and meiotic maturation, Furthermore, the Sos1 PH domain exhibited also significant synergy with insulin or coinjected normal Ras protein in induction of germinal vesicle breakdown, although it did not affect the rate of progesterone-induced maturation. These results suggest that purified, isolated PH domains retain, at least in part, their functional specificity and that Xenopus oocytes may constitute a useful biological system to analyze the functional role of the Sos1 PH domain in Ras signaling pathways. C1 NCI,CELLULAR & MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. SUNY STONY BROOK,DEPT ANESTHESIOL & PHYSIOL & BIOPHYS,STONY BROOK,NY 11794. RI Guerrero, Carmen/F-1776-2010 OI Guerrero, Carmen/0000-0002-8747-6831 NR 41 TC 11 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 26 PY 1996 VL 271 IS 30 BP 18272 EP 18276 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY935 UT WOS:A1996UY93500101 ER PT J AU Chen, XY Kang, HS Shen, LX Chamorro, M Varmus, HE Tinoco, I AF Chen, XY Kang, HS Shen, LX Chamorro, M Varmus, HE Tinoco, I TI A characteristic bent conformation of RNA pseudoknots promotes -1 frameshifting during translation of retroviral RNA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RNA; pseudoknot; NMR; frameshifting; retroviruses ID IDENTIFICATION; SIGNAL; VIRUS AB The structures of four different RNA pseudoknots that provide one of the signals required for ribosomal frameshifting in mouse mammary tumor virus have been determined by NMR. The RNA pseudoknots have similar sequences and assume similar secondary structures, but show significantly different frameshifting efficiencies. The three-dimensional structures of one frameshifting and one non-frameshifting RNA pseudoknot had been determined previously by our group. Here we determine the structures of two new RNA pseudoknots, and relate the structures of all four pseudoknots to their frameshifting abilities. The two efficient frameshifting pseudoknots adopt characteristic bent conformations with stem 1 bending towards the major groove of stem 2. In contrast, the two poor frameshifting pseudoknots have structures very different from each other and from the efficient frameshifters. One has linear, coaxially stacked stems, the other has stems twisted and bent, but in the opposite direction to the efficient frameshifters. Changes in loop size that favor bending (shorter loops) increase frameshifting efficiency; longer loops that allow linear arrangement of the stems decrease frameshifting. Frameshifting pseudoknots in feline immunodeficiency virus and simian retrovirus have different loop sequences, but the sequences at their stem junctions imply the same bent conformation as in the mouse mammary tumor viral RNA. The requirement for a precise pseudoknot conformation for efficient frameshifting strongly implies that a specific interaction occurs between the viral RNA pseudoknot and the host protein-synthesizing machinery. (C) 1996 Academic Press Limited C1 UNIV CALIF BERKELEY,DEPT CHEM,BERKELEY,CA 94720. UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,DIV BIOL STRUCT,BERKELEY,CA 94720. SRI INT,DIV LIFE SCI,MENLO PK,CA 94025. UNIV CALIF SANTA CRUZ,SINSHEIMER LABS,SANTA CRUZ,CA 95064. NCI,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA12705]; NIGMS NIH HHS [GM10840] NR 14 TC 83 Z9 85 U1 0 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 26 PY 1996 VL 260 IS 4 BP 479 EP 483 DI 10.1006/jmbi.1996.0415 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY986 UT WOS:A1996UY98600001 PM 8759314 ER PT J AU Mosimann, SC Newton, DL Youle, RJ James, MNG AF Mosimann, SC Newton, DL Youle, RJ James, MNG TI X-ray crystallographic structure of recombinant eosinophil-derived neurotoxin at 1.83 angstrom resolution SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ribonuclease; sulfate; cytotoxin; eosinophil cationic protein ID CRYSTAL-STRUCTURE; RIBONUCLEASE SUPERFAMILY; CATIONIC PROTEIN; PURIFICATION; ANGIOGENIN; REFINEMENT; COMPLEX; LINKAGE; RNASE AB The X-ray crystallographic structure of recombinant eosinophil-derived neurotoxin (rEDN) has been determined by molecular replacement methods and refined at 1.83 Angstrom resolution to a conventional R-factor (=Sigma parallel to F-o\-\F-c parallel to/Sigma\F-o\) of 0.152 with excellent stereochemistry. The molecular model of rEDN contains all 1081 non-hydrogen protein atoms, two non-covalently bound sulfate anions and 121 ordered solvent molecules. The polypeptide fold of rEDN is related to those observed in the homologous structures of RNase A, Onconase and angiogenin. rEDN is one of the largest members of the pyrimidine-specific ribonuclease superfamily of vertebrates and has small insertions in four of its seven loop structures and a large insertion from Asp115 to Tyr123. The non-covalently bound SO4(A) and SO4(B) anions occupy phosphate-binding subsites of rEDN. The active site SO4(A) anion makes contacts in rEDN that are similar to those in RNase A and involve the side-chain atoms of Gln14, His15 and His129, and the NH group of Leu130. The SO4(B) anion makes contacts with the side-chain atoms of Arg36 and Asn39 and the main-chain atoms of; Asn39 and Gln40. The equivalent residues of RNase A cannot make contacts similar to those observed in rEDN, The SO4(B) binding site of rEDN likely corresponds to the P--1 subsite and may be representative of how other homologous RNases bind the P--1 phosphate. (C) 1996 Academic Press Limited C1 UNIV ALBERTA,DEPT BIOCHEM,MRC,GRP PROT STRUCT & FUNCT,EDMONTON,AB T6G 2H7,CANADA. NCI,FREDERICK CANC RES & DEV CTR,LAB BIOCHEM PHYSIOL,FREDERICK,MD 21702. NINCDS,BIOCHEM SECT,SURG NEUROL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 41 TC 78 Z9 79 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 26 PY 1996 VL 260 IS 4 BP 540 EP 552 DI 10.1006/jmbi.1996.0420 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY986 UT WOS:A1996UY98600006 PM 8759319 ER PT J AU Tsai, CJ Lin, SL Wolfson, HJ Nussinov, R AF Tsai, CJ Lin, SL Wolfson, HJ Nussinov, R TI A dataset of protein-protein interfaces generated with a sequence-order-independent comparison technique SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE dataset of subunit interfaces; hydrophobic interactions; protein folding; protein-protein recognition; protein cores ID MULTIDIMENSIONAL NMR; CRYSTAL-STRUCTURE; RECOGNITION; RESOLUTION; SURFACE; DOMAIN; EVOLUTION; SUBUNIT AB White there are a number of-structurally non-redundant datasets of protein monomers, there is none of protein-protein interfaces. Yet, the availability of such a dataset is expected to provide an added insight into a number of investigations. First and foremost among these is analyzing the interfaces to obtain their prevailing architectures, the forces that account for the protein-protein associations and their packing considerations. Their comparisons with those of the monomers are likely to shed additional light on protein-protein recognition on the one hand and on the folding of the polypeptide chain on the other. Docking simulations are also expected to benefit from the existence of such a dataset. A major stumbling block to the generation of a dataset of interfaces has been that the interface is composed of at least two chains. Furthermore, in the interfaces, each of the chains might be represented by non-contiguous pieces. Their order in the interfaces being compared might be different as well. This discontinuity stems from the definition of an interface. An interface consists of interacting residues between the chains, and those that-are in their vicinity in the supporting scaffold, within a certain distance threshold. This necessarily yields unordered fragments, as well as isolated residues. Our novel, efficient, sequence-order-independent structural comparison technique is ideally suited to handle the task of the generation of a library of structurally non-redundant protein-protein interfaces. As it is computer-vision based, it views atoms as collections of points in space, disregarding their chain connectivity. in this work, 351 interface-families are created. Comparisons of the interfaces, and separately, of the chains which contribute to them, yield some interesting cases. In one of the cases, while two interfaces are similar, the structure of only one of the two chains is similar between the two complexes. The structure of the second chain of the first complex differs from that of the second chain of the second complex. Here the structure of the cleft in the first chain dictates the specific binding interactions. Ln another case, while the interfaces in the two complexes are similar, both chains composing them differ between the complexes. Lastly, the chains composing the complexes are similar, but the interfaces are dissimilar, providing a set of data for investigations of the favorable orientations of protein-protein associations. (C) 1996 Academic Press Limited C1 TEL AVIV UNIV,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES FACIL,MATH BIOL LAB,SAIC,FREDERICK,MD 21702. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [1-CO-74102] NR 26 TC 132 Z9 134 U1 1 U2 7 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 26 PY 1996 VL 260 IS 4 BP 604 EP 620 DI 10.1006/jmbi.1996.0424 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY986 UT WOS:A1996UY98600010 PM 8759323 ER PT J AU Haynes, BF Pantaleo, G Fauci, AS AF Haynes, BF Pantaleo, G Fauci, AS TI HIV quasispecies and resampling - Response SO SCIENCE LA English DT Letter C1 NIAID,NIH,BETHESDA,MD 20892. RP Haynes, BF (reprint author), DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 26 PY 1996 VL 273 IS 5274 BP 416 EP 416 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY983 UT WOS:A1996UY98300006 ER PT J AU Schrock, E duManoir, S Veldman, T Schoell, B Wienberg, J FergusonSmith, MA Ning, Y Ledbetter, DH BarAm, I Soenksen, D Garini, Y Ried, T AF Schrock, E duManoir, S Veldman, T Schoell, B Wienberg, J FergusonSmith, MA Ning, Y Ledbetter, DH BarAm, I Soenksen, D Garini, Y Ried, T TI Multicolor spectral karyotyping of human chromosomes SO SCIENCE LA English DT Article ID HYBRIDIZATION AB The simultaneous and unequivocal discernment of all human chromosomes in different colors would be of significant clinical and biologic importance. Whole-genome scanning by spectral karyotyping allowed instantaneous visualization of defined emission spectra for each human chromosome after fluorescence in situ hybridization, By means of computer separation (classification) of spectra, spectrally overlapping chromosome-specific DNA probes could be resolved, and all human chromosomes were simultaneously identified. C1 UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,ENGLAND. TEL AVIV UNIV,DEPT CELL RES & IMMUNOL,IL-69978 TEL AVIV,ISRAEL. APPL SPECTRAL IMAGING INC,CARLSBAD,CA 92009. APPL SPECTRAL IMAGING LTD,IL-10551 MIGDAL HAEMEQ,ISRAEL. NIH,DIAGNOST DEV BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 12 TC 1227 Z9 1275 U1 6 U2 55 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 26 PY 1996 VL 273 IS 5274 BP 494 EP 497 DI 10.1126/science.273.5274.494 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY983 UT WOS:A1996UY98300039 PM 8662537 ER PT J AU VanSchaick, EA Jacobson, KA Kim, HO IJzerman, AP Danhof, M AF VanSchaick, EA Jacobson, KA Kim, HO IJzerman, AP Danhof, M TI Hemodynamic effects and histamine release elicited by the selective adenosine A(3) receptor agonist 2-Cl-IB-MECA in conscious rats SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE adenosine A(3) receptor; hemodynamics; histamine release; tachyphylaxis; 2-chloro-N-6-(3-iodobenzyl)adenosine-5-N(2-Cl-IB-MECA); rat, conscious ID MAST-CELLS; HYPOTENSION; CLONING AB The hemodynamic effects of the novel, selective adenosine A(3) receptor agonist 2-chloro-N-6-(3-iodobenzyl)adenosine-5'-N-methyl-carboxamide (2-Cl-IB-MECA) were investigated in conscious rats. Intravenous administration of 200 mu g/kg 2-Cl-IB-MECA resulted in a short-lasting hypotension, which was accompanied by a 50-100-fold increase in plasma histamine concentrations. Administration of a second dose of 2-Cl-IB-MECA did not elicit any hemodynamic effects. Also no histamine release was observed after the second dose. The observation of rapid tachyphylaxis in combination with histamine release suggests that mast cell mediator release plays a key role in the hemodynamic effects of adenosine A(3) receptor agonists. C1 LEIDEN UNIV,LEIDEN AMSTERDAM CTR DRUG RES,DIV PHARMACOL,NL-2300 RA LEIDEN,NETHERLANDS. LEIDEN UNIV,LEIDEN AMSTERDAM CTR DRUG RES,DIV MED CHEM,NL-2300 RA LEIDEN,NETHERLANDS. NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20898. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 14 TC 57 Z9 58 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 JUL 25 PY 1996 VL 308 IS 3 BP 311 EP 314 DI 10.1016/0014-2999(96)00373-1 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VB571 UT WOS:A1996VB57100014 PM 8858305 ER PT J AU MazzolaPomietto, P Aulakh, CS Murphy, DL AF MazzolaPomietto, P Aulakh, CS Murphy, DL TI NMDA receptor antagonists block development of tolerance to m-CPP-induced increases in ACTH concentrations in rats SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE 5,7-dichlorokynurenic acid; HA-966 (3-amino-1-hydroxy-2-pyrrolidone); dizocilpine; phenyclidine; ifenprodil; CPP ((+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid); 5-HT2C receptor ID D-ASPARTATE ANTAGONIST; LOCOMOTOR-ACTIVITY; 5-HT1C RECEPTORS; SEROTONIN; PHENCYCLIDINE; NEUROENDOCRINE; CORTICOSTERONE; HYPOPHAGIA; ACTIVATION; SECRETION AB We have recently demonstrated that a single administration of m-chlorophenylpiperazine (m-CPP, a preferential 5-HT2C receptor agonist) produces tolerance to its stimulatory effect on adrenocorticotropic hormone (ACTH) concentrations when challenged 24 h later with the same dose of m-CPP. In the present study, we studied the effects of pretreatment with various N-methyl-D-aspartate (NMDA) receptor antagonists on development of tolerance to m-CPP's stimulatory effect on ACTH concentrations. Pretreatment with various NMDA receptor antagonists such as 5,7-dichlorokynurenic acid (1.0 mg/kg), 3-amino-1-hydroxy-pyrrolidone (1.0 mg/kg), dizocilpine (0.1 mg/kg) and ifenprodil (1.0 mg/kg) injected 30 min before the first injection of m-CPP (2.5 mg/kg) blocked development of tolerance to m-CPP's stimulatory effect on ACTH concentrations in rats injected 24 h later with the same dose (2.5 mg/kg) of m-CPP. These findings suggest that tolerance to postsynaptic 5-HT2C receptor-mediated response is initiated though stimulation of NMDA receptor complex and, furthermore, demonstrate a functional interaction between the 5-HT and glutamate systems. RP MazzolaPomietto, P (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,10 CTR DR MSC 1264,BETHESDA,MD 20892, USA. NR 25 TC 2 Z9 2 U1 0 U2 0 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 JUL 25 PY 1996 VL 308 IS 3 BP 329 EP 333 DI 10.1016/0014-2999(96)00353-6 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VB571 UT WOS:A1996VB57100017 PM 8858308 ER PT J AU Jin, DY Lyu, MS Kozak, CA Jeang, KT AF Jin, DY Lyu, MS Kozak, CA Jeang, KT TI Function of 14-3-3 proteins SO NATURE LA English DT Letter ID GENE C1 NIAID,MOLEC MICROBIOL LAB,NIH,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008; OI Reiner, Orly/0000-0001-7560-9599 NR 14 TC 5 Z9 6 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUL 25 PY 1996 VL 382 IS 6589 BP 308 EP 308 DI 10.1038/382308a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY950 UT WOS:A1996UY95000035 PM 8684458 ER PT J AU Yang, XJ Ogryzko, VV Nishikawa, J Howard, BH Nakatani, Y AF Yang, XJ Ogryzko, VV Nishikawa, J Howard, BH Nakatani, Y TI A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A SO NATURE LA English DT Article ID NUCLEAR-PROTEIN CBP; TRANSCRIPTIONAL ADAPTERS; ACTIVATION; YEAST; CREB; DNA; NUCLEOSOME; DOMAINS; CELLS; P300 AB The adenoviral oncoprotein E1A induces progression through the cell cycle by binding to the products of the p300/CBP and retinoblastoma gene families. A new cellular p300/CBP-associated factor (P/CAF) having intrinsic histone acetylase activity has been identified that competes with E1A. Exogenous expression of P/CAF in HeLa cells inhibits cell-cycle progression and counteracts the mitogenic activity of E1A. E1A disturbs the normal cellular interaction between p300/CBP and its associated histone acetylase. C1 NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 36 TC 1220 Z9 1243 U1 5 U2 23 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUL 25 PY 1996 VL 382 IS 6589 BP 319 EP 324 DI 10.1038/382319a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY950 UT WOS:A1996UY95000041 PM 8684459 ER PT J AU Hansson, LE Nyren, O Hsing, AW Bergstrom, R Josefsson, S Chow, WH Fraumeni, JF Adami, HO AF Hansson, LE Nyren, O Hsing, AW Bergstrom, R Josefsson, S Chow, WH Fraumeni, JF Adami, HO TI The risk of stomach cancer in patients with gastric or duodenal ulcer disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HELICOBACTER-PYLORI; PEPTIC-ULCER; ASCORBIC-ACID; ASPIRIN USE; CARCINOMA; ALCOHOL; DRUGS AB Background Helicobacter pylori infection, now considered to be a cause of gastric cancer, is also strongly associated with gastric and duodenal ulcer disease. The discovery of these relations has brought the long-controversial connection between peptic ulcers and gastric cancer into focus. Methods We estimated the risk of stomach cancer in a large cohort of hospitalized patients with gastric or duodenal ulcers, as recorded in the Swedish Inpatient Register between 1965 and 1983. Altogether, 57,936 patients were followed through 1989, for an average of 9.1 years. The standardized incidence ratio - the ratio of the observed number of cancers to the number expected on the basis of the incidence in the Swedish population at large - was used as a measure of relative risk. Results After peaking in the first 3 years of followup, the standardized incidence ratio for gastric cancer among 29,287 patients with gastric ulcers leveled off at 1.8 (95 percent confidence interval, 1.6 to 2.0) and remained significantly increased throughout followup, which was as long as 24 years for some patients. Prepyloric ulcer, diagnosed in 8646 patients, was not associated with a significant excess risk (standardized incidence ratio, 1.2; 95 percent confidence interval, 0.8 to 1.6). In the cohort of patients with duodenal ulcers (24,456 patients), the incidence of gastric cancer was significantly lower than expected. After the second year of follow-up, the standardized incidence ratio was only 0.6 (95 percent confidence interval, 0.4 to 0.7) and remained stable thereafter. Conclusions Gastric ulcer disease and gastric cancer have etiologic factors in common. A likely cause of both is atrophic gastritis induced by H. pylori. By contrast, there appear to be factors associated with duodenal ulcer disease that protect against gastric cancer. (C) 1996, Massachusetts Medical Society. C1 UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. UNIV UPPSALA HOSP,DEPT STAT,S-75185 UPPSALA,SWEDEN. MORA HOSP,DEPT SURG,MORA,SWEDEN. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. INT EPIDEMIOL INST,ROCKVILLE,MD. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. FU PHS HHS [85636-05] NR 53 TC 410 Z9 423 U1 1 U2 12 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 25 PY 1996 VL 335 IS 4 BP 242 EP 249 DI 10.1056/NEJM199607253350404 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UZ532 UT WOS:A1996UZ53200004 PM 8657240 ER PT J AU Nelson, KB Dambrosia, J Grether, JK AF Nelson, KB Dambrosia, J Grether, JK TI Electronic fetal monitoring in predicting cerebral palsy - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 CALIF DEPT HLTH SERV,EMERYVILLE,CA 94608. RP Nelson, KB (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 25 PY 1996 VL 335 IS 4 BP 288 EP 288 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UZ532 UT WOS:A1996UZ53200025 ER PT J AU Richmond, J Berman, BM Docherty, JP Goldstein, LB Kaplan, G Keil, JE Krippner, S Lyne, S Mosteller, F OConnor, BB Rudy, EB Schatzberg, AF Friedman, R Altman, F Benson, H Elliott, JM Ferguson, JH Gracely, R Greene, A Haddox, JD Hall, WH Hauri, PJ Helzner, EC Kaufmann, PG Kiley, JP Leveck, MD McCutchen, CB Monjan, AA Pillemer, SR MacArthur, JD Sherman, C Spencer, J Varricchio, CG AF Richmond, J Berman, BM Docherty, JP Goldstein, LB Kaplan, G Keil, JE Krippner, S Lyne, S Mosteller, F OConnor, BB Rudy, EB Schatzberg, AF Friedman, R Altman, F Benson, H Elliott, JM Ferguson, JH Gracely, R Greene, A Haddox, JD Hall, WH Hauri, PJ Helzner, EC Kaufmann, PG Kiley, JP Leveck, MD McCutchen, CB Monjan, AA Pillemer, SR MacArthur, JD Sherman, C Spencer, J Varricchio, CG TI Integration of behavioral and relaxation approaches into the treatment of chronic pain and insomnia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Objective.-To provide physicians with a responsible assessment of the integration of behavioral and relaxation approaches into the treatment of chronic pain and insomnia. Participants.-A nonfederal, nonadvocate, 12-member panel representing the fields of family medicine, social medicine, psychiatry, psychology, public health, nursing, and epidemiology. In addition, 23 experts in behavioral medicine, pain medicine, sleep medicine, psychiatry, nursing, psychology, neurology, and behavioral and neurosciences presented data to the panel and a conference audience of 528 during a 1 1/2-day public session. Questions and statements from conference attendees were considered during the open session. Closed deliberations by the panel occurred during the remainder of the second day and the morning of the third day. Evidence.-The literature was searched through MEDLINE, and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. Assessment Process.-The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. Conclusions.-A number of well-defined behavioral and relaxation interventions now exist and are effective in the treatment of chronic pain and insomnia. The panel found strong evidence for the use of relaxation techniques in reducing chronic pain in a variety of medical conditions as well as strong evidence for the use of hypnosis in alleviating pain associated with cancer. The evidence was moderate for the effectiveness of cognitive-behavioral techniques and biofeedback in relieving chronic pain. Regarding insomnia, behavioral techniques, particularly relaxation and biofeedback, produce improvements in some aspects of sleep, but it is questionable whether the magnitude of the improvement in sleep onset and total sleep time are clinically significant. C1 UNIV MARYLAND,SCH MED,DEPT FAMILY MED,DIV COMPLEMENTARY MED,BALTIMORE,MD 21201. CORNELL UNIV,NEW YORK HOSP,WHITE PLAINS,NY 10605. CORNELL UNIV,COLL MED,DEPT PSYCHIAT,WHITE PLAINS,NY 10605. DUKE UNIV,MED CTR,DURHAM VA MED CTR,DEPT MED,DIV NEUROL,DURHAM,NC. DUKE UNIV,MED CTR,DURHAM VA MED CTR,CTR HLTH POLICY RES & EDUC,DURHAM,NC. GEORGETOWN UNIV,SCH MED,DEPT FAMILY & COMMUNITY MED,WASHINGTON,DC 20057. FAMILY PRACTICE ASSOCIATES,ARLINGTON,VA. MED UNIV S CAROLINA,DEPT BIOSTAT EPIDEMIOL & SYST SCI,CHARLESTON,SC 29425. SAYBROOK INST GRAD SCH & RES CTR,SAN FRANCISCO,CA. CHICAGO DEPT PUBL HLTH,CHICAGO,IL. HARVARD UNIV,DEPT STAT,CAMBRIDGE,MA 02138. HARVARD UNIV,DEPT HLTH POLICY & MANAGEMENT,CAMBRIDGE,MA 02138. MED COLL PENN & HAHNEMANN UNIV,SCH MED,DEPT COMMUNITY & PREVENT MED,PHILADELPHIA,PA 19102. UNIV PITTSBURGH,SCH NURSING,PITTSBURGH,PA 15261. STANFORD UNIV,SCH MED,DEPT PSYCHIAT,STANFORD,CA 94305. SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794. NIMH,MED RES BRANCH,DIV EPIDEMIOL & SERV RES,NIH,BETHESDA,MD 20892. DEACONESS HOSP,DIV BEHAV MED,BOSTON,MA. MIND BODY MED INST,BOSTON,MA. NIH,OFF MED APPLICAT RES,BETHESDA,MD 20892. NIDR,NEUROPATH & PAIN MEASUREMENT SECT,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. NIH,OFF ALTERNAT MED,BETHESDA,MD 20892. EMORY UNIV,SCH MED,ATLANTA,GA. NIH,OFF MED APPLICAT RES,BETHESDA,MD 20892. MAYO CLIN & MAYO FDN,MAYO MED SCH,ROCHESTER,MN 55905. MAYO CLIN,INSOMNIA PROGRAM,DEPT PSYCHOL,SLEEP DISORDERS CTR,ROCHESTER,MI. NHLBI,BEHAV MED SCI RES GRP,BETHESDA,MD 20892. NHLBI,NATL CTR SLEEP DISORDERS CTR,NIH,BETHESDA,MD 20892. NINR,DIV EXTRAMURAL PROGRAMS,NIH,BETHESDA,MD. NINCDS,EPILEPSY BRANCH,DIV CONVULS DEV & NEUROMUSCULAR DISORDERS,NIH,BETHESDA,MD 20892. NIA,NEUROBIOL AGING PROGRAM,NIH,BETHESDA,MD 20892. NIA,NEUROSCI & NEUROPSYCHOL AGING PROGRAM,NIH,BETHESDA,MD 20892. NIAMSD,OFF PREVENT EPIDEMIOL & CLIN APPLICAT,NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT SOCIAL MED,BOSTON,MA 02115. NIH,OFF MED APPLICAT RES,BETHESDA,MD 20892. NIH,OFF ALTERNAT MED,BETHESDA,MD 20892. NCI,COMMUNITY ONCOL & REHABIL BRANCH,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892. RP Richmond, J (reprint author), HARVARD UNIV,SCH MED,DEPT SOCIAL MED,BOSTON,MA 02115, USA. OI Bradley, Laurence/0000-0002-1206-2263 NR 0 TC 171 Z9 173 U1 5 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 24 PY 1996 VL 276 IS 4 BP 313 EP 318 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UX583 UT WOS:A1996UX58300037 ER PT J AU Tjandra, N Szabo, A Bax, A AF Tjandra, N Szabo, A Bax, A TI Protein backbone dynamics and N-15 chemical shift anisotropy from quantitative measurement of relaxation interference effects SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MAGNETIC-RESONANCE RELAXATION; MODEL-FREE APPROACH; CROSS-CORRELATION; HUMAN UBIQUITIN; SECONDARY STRUCTURE; NMR-SPECTROSCOPY; SPIN RELAXATION; DIPOLAR; MACROMOLECULES; TENSORS AB Cross-correlation between N-15-H-1 dipolar interactions and N-15 chemical shift anisotropy (CSA) gives rise to different relaxation rates of the doublet components of N-15-{H-1} peptide backbone amides. A simple scheme for quantitative measurement of this effect is described which yields information on the magnitude of the CSA from the relative intensities of H-1-N-15 correlations obtained with two slightly different pulse schemes. The method is applied to a sample of uniformly N-15-enriched ubiquitin and measurements conducted at two field strengths (8.5 and 14 T) yield identical results. The degree of relaxation interference correlates with the isotropic N-15 chemical shift and results indicate that the sum of the most shielded principal components of the CSA tensor is nearly invariant to structural differences in the polypeptide backbone. The relaxation interference is directly proportional to the generalized order parameter, S-2, of the peptide backbone amides, and this relation can be utilized to obtain approximate values for these order parameters. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Szabo, Attila/H-3867-2012 NR 40 TC 289 Z9 289 U1 1 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 24 PY 1996 VL 118 IS 29 BP 6986 EP 6991 DI 10.1021/ja960510m PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA UY871 UT WOS:A1996UY87100022 ER PT J AU Hagedorn, M Hsu, EW Pilatus, U Wildt, DE Rall, WF Blackband, SJ AF Hagedorn, M Hsu, EW Pilatus, U Wildt, DE Rall, WF Blackband, SJ TI Magnetic resonance microscopy and spectroscopy reveal kinetics of cryoprotectant permeation in a multicompartmental biological system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE zebrafish; yolk syncytial layer; conservation; cryopreservation ID YOLK SYNCYTIAL LAYER; NMR MICROSCOPY; DIFFUSION; CELLS; PERMEABILITY; FUNDULUS; ECHO AB Successful cryopreservation of most multicompartmental biological systems has not been achieved. One prerequisite for success is quantitative information on cryoprotectant permeation into and amongst the compartments, This report describes direct measurements of cryoprotectant permeation into a multicompartmental system using chemical shift selective magnetic resonance (MR) microscopy and MR spectroscopy. We used the developing zebrafish embryo as a model For studying these complex systems because these embryos are composed of two membrane-limited compartments: (i) a large yolk (surrounded by the yolk syncytial layer) and (ii) differentiating blastoderm cells (each surrounded by a plasma membrane). MR images of the spatial distribution of three cryoprotectants (dimethyl sulfoxide, propylene glycol, and methanol) demonstrated that methanol permeated the entire embryo within 15 min, In contrast, the other cryoprotectants exhibited little or no permeation over 2.5 h. MR spectroscopy and microinjections of cryoprotectants into the yolk inferred that the yolk syncytial layer plays a critical role in limiting the permeation of some cryoprotectants throughout the embryo. This study demonstrates the power of MR technology combined with micromanipulation for elucidating key physiological factors in cryobiology. C1 SMITHSONIAN INST,CONSERVAT & RES CTR,WASHINGTON,DC 20008. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOMED ENGN,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,NIH,BETHESDA,MD 20892. UNIV HULL,DEPT MED PHYS,KINGSTON HULL HU3 2JZ,N HUMBERSIDE,ENGLAND. RP Hagedorn, M (reprint author), SMITHSONIAN INST,NATL ZOOL PK,WASHINGTON,DC 20008, USA. FU NCRR NIH HHS [R29 RR08769] NR 24 TC 76 Z9 82 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 1996 VL 93 IS 15 BP 7454 EP 7459 DI 10.1073/pnas.93.15.7454 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000007 PM 8755494 ER PT J AU Chipman, PR AgbandjeMcKenna, M Kajigaya, S Brown, KE Young, NS Baker, TS Rossmann, MG AF Chipman, PR AgbandjeMcKenna, M Kajigaya, S Brown, KE Young, NS Baker, TS Rossmann, MG TI Cryo-electron microscopy studies of empty capsids of human parvovirus B19 complexed with its cellular receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; CANINE PARVOVIRUS; CRYOELECTRON MICROSCOPY; IMAGE-RECONSTRUCTION; INFECTION; ANTIBODIES; PARTICLES; FRAGMENT; VIRIONS; CELLS AB The three-dimensional structures of human parvovirus B19 VP2 capsids, alone and complexed with its cellular receptor, globoside, have been determined to 26 Angstrom resolution. The B19 capsid structure, reconstructed from cryo-electron micrographs of vitrified specimens, has depressions on the icosahedral 2-fold and 3-fold axes, as well as a canyon-like region around the 5-fold axes. Similar results had previously been found in an 8 Angstrom resolution map derived from x-ray diffraction data. Other parvoviral structures have a cylindrical channel along the 5-fold icosahedral axes, whereas density covers the 5-fold axes in B19. The glycolipid receptor molecules bind into the depressions on the 5-fold axes of the B19:globoside complex. A model of the tetrasaccharide component of globoside, organized as a trimeric fiber, fits well into the difference density representing the globoside receptor. Escape mutations to neutralizing antibodies map onto the capsid surface at regions immediately surrounding the globoside attachment sites. The proximity of the antigenic epitopes to the receptor site suggests that neutralization of virus infectivity is caused by preventing attachment of viruses to cells. C1 PURDUE UNIV,DEPT BIOL SCI,W LAFAYETTE,IN 47907. NHLBI,NIH,BETHESDA,MD 20892. FU NIAID NIH HHS [R01 AI033468, AI 11219, AI 33468, P01 AI035212]; NIGMS NIH HHS [GM 33050] NR 34 TC 71 Z9 72 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 1996 VL 93 IS 15 BP 7502 EP 7506 DI 10.1073/pnas.93.15.7502 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000016 PM 8755503 ER PT J AU Cassetti, MC Moss, B AF Cassetti, MC Moss, B TI Interaction of the 82-kDa subunit of the vaccinia virus early transcription factor heterodimer with the promoter core sequence directs downstream DNA binding of the 70-kDa subunit SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein-DNA crosslinking; DNA bending; DNA-binding specificity; aryl azide ID DEPENDENT ATPASE ACTIVITY; EARLY GENE-TRANSCRIPTION; RNA-POLYMERASE; CONTACTS; SPECIFICITY; COMPLEX AB The vaccinia virus early transcription factor (VETF), a heterodimeric protein composed of 82- and 70-kDa subunits, interacts with viral early promoters at both a sequence-specific core region upstream and a sequence-independent region downstream of the RNA start site, To determine the VETF subunit-promoter interactions, P-32-labeled DNA targets were chemically synthesized with uniquely positioned phosphorothioates to which azidophenacyl bromide moieties were coupled. After incubating the derivatized promoter with VETF and exposing the complex to 302-nm light, the protein was denatured and the individual subunits with or without covalently bound DNA were isolated with specific antiserum and analyzed by SDS/polyacrylamide gel electrophoresis. Using a set of 26 duplex probes, with uniquely positioned aryl azide moieties on the coding or template strands, we found that the 82-kDa subunit interacted primarily with the core region of the promoter, whereas the 70-kDa subunit interacted with the downstream region, Nucleotide substitutions in the core region that downregulate transcription affected the binding of both subunits: the 82-kDa subunit no longer exhibited specificity for upstream regions of the promoter but also bound to downstream regions, whereas the binding of the 70-kDa subunit was abolished even though the mutations were far upstream of its binding site, These results suggested mechanisms by which the interaction of the 82-kDa subunit with the core sequence directs binding of the 70-kDa subunit to DNA downstream. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NR 24 TC 17 Z9 17 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 1996 VL 93 IS 15 BP 7540 EP 7545 DI 10.1073/pnas.93.15.7540 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000023 PM 8755510 ER PT J AU Feng, YX Copeland, TD Henderson, LE Gorelick, RJ Bosche, WJ Levin, JG Rein, A AF Feng, YX Copeland, TD Henderson, LE Gorelick, RJ Bosche, WJ Levin, JG Rein, A TI HIV-1 nucleocapsid protein induces ''maturation'' of dimeric retroviral RNA in vitro SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HAMMERHEAD RIBOZYME CATALYSIS; MURINE LEUKEMIA-VIRUS; NUCLEIC-ACIDS; CIS ELEMENTS; ZINC FINGERS; VIRAL-RNA; BINDING; SEQUENCES; GAG AB After a retrovirus particle is released from the cell, the dimeric genomic RNA undergoes a change in conformation, We have previously proposed that this change, termed maturation of the dimer, is due to the action of nucleocapsid (NC) protein on the RNA within the virus particle. We now report that treatment of a 345-base synthetic fragment of Harvey sarcoma virus RNA with recombinant or synthetic HIV-1 NC protein converts a less stable form of dimeric RNA to a more stable form, This phenomenon thus appears to reproduce the maturation of dimeric retroviral RNA in a completely defined system in vitro. To our knowledge, maturation of dimeric RNA within a retrovirus particle is the first example of action of an ''RNA chaperone'' protein in vivo. Studies with mutant NC proteins suggest that the activity depends upon basic amino acid residues flanking the N-terminal zinc finger and upon residues within the N-terminal finger, including an aromatic amino acid, but do not require the zinc finger structures themselves. C1 NCI,FREDERICK CANC RES & DEV CTR,RETROVIRAL GENET SECT,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SPECIAL PROGRAM PROT CHEM,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE PROGRAM,SAIC,FREDERICK,MD 21702. NICHHD,MOLEC GENET LAB,NIH,BETHESDA,MD 20892. NR 30 TC 146 Z9 147 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 1996 VL 93 IS 15 BP 7577 EP 7581 DI 10.1073/pnas.93.15.7577 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000030 PM 8755517 ER PT J AU Lujan, HD Mowatt, MR Byrd, LG Nash, TE AF Lujan, HD Mowatt, MR Byrd, LG Nash, TE TI Cholesterol starvation induces differentiation of the intestinal parasite Giardia lamblia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE encystation; primitive eukaryote; protozoan; membrane fluidity; bile salts ID PRIMITIVE EUKARYOTE; ANIMAL INFECTIVITY; SIGNALING PATHWAY; SURFACE PROTEIN; CYST ANTIGENS; BILE-ACIDS; IN-VITRO; MEMBRANE; ENCYSTATION; INVITRO AB Giardia lamblia, like most human intestinal parasitic protozoa, sustains fundamental morphological and biochemical changes to survive outside the small intestine of its mammalian host by differentiating into an infective cyst. However, the stimulus that triggers this differentiation remains totally undefined. In this work, we demonstrate the induction of cyst formation in vitro when trophozoites are starved for cholesterol. Expression of cyst wall proteins was detected within encystation-specific secretory vesicles 90 min after the cells were placed in lipoprotein-deficient TYI-S-33 medium. Four cloned lines derived from two independent Giardia isolates were tested, and all formed cysts similarly. Addition of cholesterol, low density or very low density lipoproteins to the lipoprotein-deficient culture medium, inhibited the expression of cyst wall proteins, the generation of encystation-specific vesicles, and cyst wall biogenesis. In contrast, high density lipoproteins, phospholipids, bile salts, or fatty acids had little or no effect. These results indicate that cholesterol starvation is necessary and sufficient for the stimulation of Giardia encystation in vitro and, likely, in the intestine of mammalian hosts. RP Lujan, HD (reprint author), NIAID,PARASIT DIS LAB,NIH,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 59 TC 80 Z9 81 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 1996 VL 93 IS 15 BP 7628 EP 7633 DI 10.1073/pnas.93.15.7628 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000039 PM 8755526 ER PT J AU Medin, JA Tudor, M Simovitch, R Quirk, JM Jacobson, S Murray, GJ Brady, RO AF Medin, JA Tudor, M Simovitch, R Quirk, JM Jacobson, S Murray, GJ Brady, RO TI Correction in trans for Fabry disease: Expression, secretion, and uptake of alpha-galactosidase A in patient-derived cells driven by a high-titer recombinant retroviral vector SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-TRANSFER AB Fabry disease is an X-linked metabolic disorder due to a deficiency of alpha-galactosidase A (alpha-gal A; EC 3.2.1.22). Patients accumulate glycosphingolipids with terminal alpha-galactosyl residues that come from intracellular synthesis, circulating metabolites, or from the biodegradation of senescent cells. Patients eventually succumb to renal, cardio-, or cerebrovascular disease. No specific therapy exists. One possible approach to ameliorating this disorder is to target corrective gene transfer therapy to circulating hematopoietic cells. Toward this end, an amphotropic virus-producer cell line has been developed that produces a high titer (> 10(6) i.p. per ml) recombinant retrovirus constructed to transduce and correct target cells. Virus-producer cells also demonstrate expression of large amounts of both intracellular and secreted alpha-gal A. To examine the utility of this therapeutic vector, skin fibroblasts from Fabry patients were corrected for the metabolic defect by infection with this recombinant virus and secreted enzyme was observed. Furthermore, the secreted enzyme was found to be taken up by uncorrected cells in a mannose-6-phosphate receptor-dependent manner. In related experiments, immortalized B cell lines from Fabry patients, created as a hematologic delivery test system, were transduced. As with the fibroblasts, transduced patient B cell lines demonstrated both endogenous enzyme correction and a small amount of secretion together with uptake by uncorrected cells. These studies demonstrate that endogenous metabolic correction in transduced cells, combined with secretion, may provide a continuous source of corrective material in trans to unmodified patient bystander cells (metabolic cooperativity). C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Medin, JA (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,NIH,BLDG 10,ROOM 3D04,10 CTR DR,MSC 1260,BETHESDA,MD 20892, USA. NR 24 TC 52 Z9 52 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 1996 VL 93 IS 15 BP 7917 EP 7922 DI 10.1073/pnas.93.15.7917 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000091 PM 8755577 ER PT J AU Dunn, DE Yu, J Nagarajan, S Devetten, M Weichold, FF Medof, ME Young, NS Liu, JM AF Dunn, DE Yu, J Nagarajan, S Devetten, M Weichold, FF Medof, ME Young, NS Liu, JM TI A knock-out model of paroxysmal nocturnal hemoglobinuria: Pig-a(-) hematopoiesis is reconstituted following intercellular transfer of GPI-anchored proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryonic stem cells; embryoid bodies; developmental biology; bone marrow failure syndromes; paroxysmal nocturnal hemoglobinuria ID DECAY-ACCELERATING FACTOR; EMBRYONIC STEM-CELLS; PIG-A GENE; INVITRO DEVELOPMENT; SOMATIC MUTATIONS; MEMBRANE-PROTEINS; FACTOR CD55; FACTOR DAF; COMPLEMENT; RECEPTOR AB We created a ''knock-out'' embryonic stem cell via targeted disruption of the phosphatidylinositol glycan class A (Pig-a) gene, resulting in loss of expression of cell surface glycosyl phosphatidylinositol-anchored proteins and reproducing the mutant phenotype of the human disease paroxysmal nocturnal hemoglobinuria. Morphogenesis of Pig-a(-) embryoid bodies (EB) in vitro was grossly aberrant and, unlike EB derived from normal embryonic stem cells, Pig-A(-) EB produced no secondary hematopoietic colonies. Chimeric EB composed of control plus Pig-A(-) cells, however, appeared normal, and hematopoiesis from knock-out cells was reconstituted. Transfer in situ of glycosyl phosphatidylinositol-anchored proteins from normal to knock-out cells was demonstrated by two-color fluorescent analysis, suggesting a possible mechanism for these functional effects. Hematopoietic cells with mutated PIG-A genes in humans with paroxysmal nocturnal hemoglobinuria may be subject to comparable pathophysiologic processes and amenable to similar therapeutic protein transfer. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. RP Dunn, DE (reprint author), NHLBI,HEMATOL BRANCH,NIH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI 23598]; NIDDK NIH HHS [P01DK38181] NR 51 TC 79 Z9 80 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 1996 VL 93 IS 15 BP 7938 EP 7943 DI 10.1073/pnas.93.15.7938 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000095 PM 8755581 ER PT J AU Smith, SM Markham, RB Jeang, KT AF Smith, SM Markham, RB Jeang, KT TI Conditional reduction of human immunodeficiency virus type 1 replication by a gain-of-herpes simplex virus 1 thymidine kinase function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE virus replication; antiviral chemotherapy ID EXOTOXIN HYBRID PROTEIN; VACCINE DEVELOPMENT; INFECTION; CELLS; MICE; ISSUES; AIDS AB The development of an effective vaccine for human immunodeficiency virus type 1 (HIV-1) would be a major advance toward controlling the AIDS pandemic. Several disparate strategies for a safe and effective HIV vaccine have been proposed. Recent data suggest that loss-of-function live-attenuated virus could be a safe lentivirus vaccine. Here, we propose a gain-of-function approach that can complement loss-of-function in enhancing the safety profile of a live-attenuated virus. We describe an example in which ganciclovir (GCV) was used to treat effectively nef(-)HIV-1 engineered to express herpes simplex virus (HSV-1) thymidine kinase (TK). This treatment was found to be highly efficient in controlling HIV-1 spread in tissue culture and in a small animal (hu-PBL-SCID) model. We demonstrate that one distinct advantage of GCV-HSV-TK treatment is the elimination of integrated proviruses, a goal not easily achieved with other antiretrovirals. C1 NIAID,MOL VIROL SECT,MOLEC MICROBIOL LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOLEC MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. RI Jeang, Kuan-Teh/A-2424-2008 NR 36 TC 29 Z9 29 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 1996 VL 93 IS 15 BP 7955 EP 7960 DI 10.1073/pnas.93.15.7955 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000098 PM 8755584 ER PT J AU Hanner, M Moebius, FF Flandorfer, A Knaus, HG Striessnig, J Kempner, E Glossmann, H AF Hanner, M Moebius, FF Flandorfer, A Knaus, HG Striessnig, J Kempner, E Glossmann, H TI Purification, molecular cloning, and expression of the mammalian sigma(1)-binding site SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-8 STEROL ISOMERASE; GUINEA-PIG LIVER; RADIATION INACTIVATION; SIGMA-RECEPTORS; CHOLESTEROL-BIOSYNTHESIS; ENDOPLASMIC-RETICULUM; RAT-LIVER; BINDING POLYPEPTIDE; H-3 (+)-PENTAZOCINE; MICROSOMAL-ENZYMES AB Sigma-ligands comprise several chemically unrelated drugs such as haloperidol, pentazocine, and ditolylguanidine, which bind to a family of low molecular mass proteins in the endoplasmic reticulum. These so-railed sigma-receptors are believed to mediate various pharmacological effects of sigma-ligands by as yet unknown mechanisms. Based on their opposite enantioselectivity for benzomorphans and different molecular masses, two subtypes are differentiated. We purified the sigma(1)-binding site as a single 30-kDa protein from guinea pig liver employing the benzomorphan (+) [H-3]pentazocine and the arylazide (-) [H-3]azidopamil as specific probes. The purified (+) [H-3]pentazocine-binding protein retained its high affinity for haloperidol, pentazocine, and ditolylguanidine. Partial amino acid sequence obtained after trypsinolysis revealed no homolog to known proteins, Radiation inactivation of the pentazocine-labeled sigma(1)-binding site yielded a molecular mass of 24 +/- 2 kDa, The corresponding cDNA was cloned using degenerate oligonucleotides and cDNA library screening, Its open reading frame encoded a 25.3-kDa protein with at least one putative transmembrane segment. The protein expressed in yeast cells transformed with the cDNA showed the pharmacological characteristics of the brain and liver sigma(1)-binding site. The deduced amino acid sequence was structurally unrelated to known mammalian proteins but it shared homology with fungal proteins involved in sterol synthesis, Northern blots showed high densities of the sigma(1)-binding site mRNA in sterol-producing tissues, This is also in agreement with the known ability of sigma(1)-binding sites to interact with steroids, such as progesterone. C1 UNIV INNSBRUCK, INST BIOCHEM PHARMAKOL, A-6020 INNSBRUCK, AUSTRIA. NIAMSD, NIH, BETHESDA, MD 20892 USA. NR 61 TC 566 Z9 576 U1 3 U2 25 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 JUL 23 PY 1996 VL 93 IS 15 BP 8072 EP 8077 DI 10.1073/pnas.93.15.8072 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY930 UT WOS:A1996UY93000119 PM 8755605 ER PT J AU Palm, GJ Lubkowski, J Derst, C Schleper, S Rohm, KH Wlodawer, A AF Palm, GJ Lubkowski, J Derst, C Schleper, S Rohm, KH Wlodawer, A TI A covalently bound catalytic intermediate in Escherichia coli asparaginase: Crystal structure of a Thr-89-val mutant SO FEBS LETTERS LA English DT Article DE asparaginase II; acyl-enzyme intermediate; threonine amidohydrolase; enzymatic mechanism ID GLUTAMINASE-ASPARAGINASE; SITE; BINDING; ACINETOBACTER; MUTAGENESIS; REFINEMENT; THREONINE AB Escherichia coli asparaginase II catalyzes the hydrolysis of L-asparagine to L-aspartate via a threonine-bound acyl-enzyme intermediate, A nearly inactive mutant in which one of the active site threonines, Thr-89, was replaced by valine was constructed, expressed, and crystallized, Its structure, solved at 2.2 Angstrom resolution, shows high overall similarity to the wild-type enzyme, but an aspartyl moiety is covalently bound to Thr-12, resembling a reaction intermediate, Kinetic analysis confirms the deacylation deficiency, which is also explained on a structural basis, The previously identified oxyanion hole is described in more detail. C1 UNIV MARBURG, INST PHYSIOL CHEM, MARBURG, LAHN, GERMANY. RP Palm, GJ (reprint author), NCI, MACROMOL STRUCT LAB, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. NR 27 TC 69 Z9 75 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 22 PY 1996 VL 390 IS 2 BP 211 EP 216 DI 10.1016/0014-5793(96)00660-6 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UZ871 UT WOS:A1996UZ87100023 PM 8706862 ER PT J AU Ye, B Burke, TR AF Ye, B Burke, TR TI Synthesis of a difluorophosphonomethyl-containing phosphatase inhibitor designed from the X-ray structure of a PTP1B-bound ligand SO TETRAHEDRON LA English DT Article ID SOLID-PHASE SYNTHESIS; NONHYDROLYZABLE MIMETICS; O-PHOSPHOTYROSINE; DERIVATIVES; ANALOGS; ACIDS AB Protein-tyrosine phosphatase (PTP) inhibitors are potentially valuable pharmacological tools for studying cellular signal transduction and for therapeutic intervention. Small peptides containing the non-hydrolyzable phosphotyrosyl mimetic difluorophosphonomethyl phenylalanine (F(2)Pmp) have been shown to be extremely potent PTP inhibitors, with the fluorines increasing inhibitory potency 1000-foId relative to the unfluorinated species. The high PTP affinity of the phosphonodifluoromethyl pharmacophore has allowed the preparation of small molecule inhibitors containing this moiety, which lack any peptide component. The X-ray structure of one such inhibitor. 2-difluoromethylnaphthylphosphonic acid (6) complexed to the catalytic site of PTP1B has recently been solved. Computer assisted molecular modelling of this complex indicates that enhanced binding interactions may result by introduction of hydroxyl functionality onto the naphthalene ring system. Herein is reported the synthesis of one such inhibitor 1,1-difluoro-1-[2-(4-hydroxynaphthalenyl)]methyl]phosphonic acid (7), which is prepared in 12 steps from commercially available 1,3-dihydroxynaphthalene. The synthetic approach relies on selective hydroxyl protection and Pd-catalyzed carbonylation to introduce functionality which is subsequently elaborated into the difluorophosphonate structure. The techniques reported herein may be applicable to the preparation of other PTP inhibitors. C1 NCI,DIV BASIC SCI,MED CHEM LAB,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 17 TC 26 Z9 28 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JUL 22 PY 1996 VL 52 IS 30 BP 9963 EP 9970 DI 10.1016/0040-4020(96)00531-5 PG 8 WC Chemistry, Organic SC Chemistry GA UY361 UT WOS:A1996UY36100002 ER PT J AU Myagkikh, M Alipanah, S Markham, PD Tartaglia, J Paoletti, E Gallo, RC Franchini, G RobertGuroff, M AF Myagkikh, M Alipanah, S Markham, PD Tartaglia, J Paoletti, E Gallo, RC Franchini, G RobertGuroff, M TI Multiple immunizations with attenuated poxvirus HIV type 2 recombinants and subunit boosts required for protection of rhesus macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; ENVELOPE GLYCOPROTEIN GP160; TOXIC LYMPHOCYTES-T; VACCINIA VIRUS; CYTOTOXIC LYMPHOCYTES; CYNOMOLGUS MONKEYS; SIV INFECTION; CHALLENGE; ALVAC; NYVAC AB Vaccine protocols involving multiple immunizations with molecularly attenuated vaccinia virus (NYVAC) or naturally attenuated canarypox virus (ALVAC) HIV-2 recombinants and subunit boosts have conferred long-lasting protection against HIV-2 infection of macaques, Similar complex protocols using HIV-1 NYVAC and ALVAC recombinants and subunit boosts-have provided cross-protection against HIV-2 challenge, Here a simplified three-immunization regimen over 24 weeks was tested in 18 juvenile rhesus macaques, Twelve macaques were immunized twice with NYVAC or ALVAC recombinants carrying HIV-2 ear, gag, and pal genes. Subsequently, macaques in groups of three received either an additional recombinant immunization or an HIV-2 gp160 boost, Six control macaques received three immunizations of NYVAC or ALVAC vector alone and additionally alum at the third immunization, Macaques primed with ALVAC recombinant exhibited sporadic T cell proliferative activity, acid ail but one failed to develop neutralizing antibodies, In contrast, macaques primed with NYVAC recombinants had no T cell proliferative activity but exhibited neutralizing antibody titers (highest in the three recombinant group) that declined by the time of challenge, None of the macaques exhibited significant cytotoxic T lymphocyte activity, Following challenge at 32 weeks with HIV-2(SBL6669) all macaques became infected, Thus, the three-immunization regimen is not sufficient to confer protective immunity in the HIV-2 rhesus macaque model, However, delayed infection in macaques immunized with the NYVAC-HIV-2 recombinant may have been associated with the development of memory B cells capable of providing a neutralizing antibody response on challenge. C1 NCI,TUMOR CELL BIOL LAB 376A11,DBS,NIH,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. VIROGENET CORP,TROY,NY 12180. NR 40 TC 41 Z9 41 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 20 PY 1996 VL 12 IS 11 BP 985 EP 992 DI 10.1089/aid.1996.12.985 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UZ765 UT WOS:A1996UZ76500005 PM 8827214 ER PT J AU Pincus, SH Wehrly, K Cole, R Fang, H Lewis, GK McClure, J Conley, AJ Wahren, B Posner, MR Notkins, AL Tilley, SA Pinter, A Eiden, L Teintze, M Dorward, D Tolstikov, VV AF Pincus, SH Wehrly, K Cole, R Fang, H Lewis, GK McClure, J Conley, AJ Wahren, B Posner, MR Notkins, AL Tilley, SA Pinter, A Eiden, L Teintze, M Dorward, D Tolstikov, VV TI In vitro effects of anti-HIV immunotoxins directed against multiple epitopes on HIV type 1 envelope glycoprotein 160 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RICIN-A-CHAIN; HUMAN MONOCLONAL-ANTIBODY; INDUCED SYNCYTIUM FORMATION; EXOTOXIN HYBRID PROTEIN; RECOMBINANT SOLUBLE CD4; CD4-PSEUDOMONAS EXOTOXIN; INFECTED-CELLS; T-CELLS; PEPTIDE DERIVATIVES AB We have used a panel of anti-gp160 MAbs to construct anti-HIV immunotoxins by coupling antibodies to ricin A chain (RAG), The ability of the immunotoxins to kill HIV-1-infected cells and halt the spread of infection was tested in tissue culture on persistently and acutely infected cell lines and primary lymphocyte cultures stimulated with phytohemagglutinin (PHA blasts), Laboratory strains and clinical isolates of HIV both were tested, The constitution and antigen-binding capacity of the immunotoxins mere confirmed by ELISA and indirect immunofluorescence. Immunotoxins that bind epitopes exposed on the cell surface effectively killed persistently infected cells, although killing was not directly proportional to binding of immunotoxin to cell. The activity of anti-gp41, but not anti-gp120, immunotoxins was markedly enhanced in the presence of soluble CD4 or peptides corresponding to the CDR3 region of CD4, CD4-mediated enhancement of anti-gp41 immunotoxin activity was observed for laboratory strains neutralized by sCD4 and for clinical isolates that were resistant to neutralization by sCD4, Immunotoxin action was potentiated by brefeldin A, bafilomycin A1, cortisone, and an amphipathic fusion peptide, but not by cytochalasin D, nocodazol, monodansyl cadaverine, or trans-retinoic acid. Anti-HIV immunotoxins are useful tools with which to study the functional expression of gp120/gp41 antigens on the surface of HIV-infected cells, as well as potential AIDS therapeutics, Because these studies relate to the accessibility of viral antigens to antibody-mediated attack, these studies also have relevance for vaccine development. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NIAID,ROCKY MT LABS,ELECTRON MICROSCOPY BRANCH,HAMILTON,MT 59840. UNIV MARYLAND,SCH MED,BALTIMORE,MD 20201. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. MERCK SHARP & DOHME LTD,RES LABS,W POINT,PA 19486. KAROLINSKA INST,S-105 STOCKHOLM,SWEDEN. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. NIDR,NIH,BETHESDA,MD 20892. NIMH,NIH,BETHESDA,MD 20892. PUBL HLTH RES INST,NEW YORK,NY 10016. MONTANA STATE UNIV,BOZEMAN,MT 59717. RP Pincus, SH (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. OI Eiden, Lee/0000-0001-7524-944X; Tolstikov, Vladimir/0000-0002-0445-884X NR 57 TC 22 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 20 PY 1996 VL 12 IS 11 BP 1041 EP 1051 DI 10.1089/aid.1996.12.1041 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UZ765 UT WOS:A1996UZ76500011 PM 8827220 ER PT J AU Clerici, M Balotta, C Meroni, L Ferrario, E Riva, C Trabattoni, D Ridolfo, A Villa, M Shearer, GM Moroni, M Galli, M AF Clerici, M Balotta, C Meroni, L Ferrario, E Riva, C Trabattoni, D Ridolfo, A Villa, M Shearer, GM Moroni, M Galli, M TI Type 1 cytokine production and low prevalence of viral isolation correlate with long-term nonprogression in HIV infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; T-CELLS; DISEASE PROGRESSION; CHILDREN; DYSFUNCTION; DEPLETION; SURVIVAL; INDIVIDUALS; ELEVATION AB Cytokine production, prevalence of viral isolation, and surface marker expression of peripheral blood mononuclear cells (PBMCs) were analyzed in HIV+ individuals with different patterns of disease progression to establish correlations between these parameters, Thus, mitogen-stimulated in vitro production of interferon gamma (IFN-gamma) and interleukin 2 (IL-2) (type 1 cytokines), and of IL-4 and IL-10 (type 2 cytokines) as well as prevalence of viral isolation were evaluated in 26 HIV+ long-term nonprogressors (LTNPs), in 28 HIV+ patients with progressive HIV infection (PI), and in 24 HIV-seronegative controls (HCs), Surface expression of activation and nonactivation markers was also analyzed in a group of these donors, We report that (1) IL-2 and IFN-gamma production is reduced and IL-4 and IL-10 production is increased in PI patients compared to HCs and LTNPs; (2) prevalence of HN isolation is lower in; LTNPs compared to PI, and the primary viral isolates in LTNPs show a slow/low (S/L) phenotype; and (3) the elevated production of type 2 cytokines is paralleled by an increase in CD57(+)CD4(+)CD7(-) lymphocytes, Thus, whereas a high IL-2, high IFN-gamma/low IL-4, low IL-10 cytokine production pattern is present in HC and in LTNP HIV+, progression of HIV infection is associated with a low IL-2 low IFN-gamma/high IL-4, high IL-10 cytokine profile; increased prevalence of HIV isolation; and an augmented percentage of CD57(+)CD4(+)CD7(-) lymphocytes. These findings further confirm that a dominant type 1 cytokine profile together with reduced prevalence of virus isolation is associated with lack of progression in HIV infection. C1 UNIV MILAN,OSPED L SACCO,CLIN MALATTIE INFETT,PADIGLIONE LITA,I-20157 MILAN,ITALY. NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RP Clerici, M (reprint author), UNIV MILAN,OSPED L SACCO,CATTEDRA IMMUNOL,PADIGLIONE LITA,VIA GB GRASSI,I-20157 MILAN,ITALY. RI Trabattoni, Daria/G-7424-2012 NR 44 TC 82 Z9 83 U1 1 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 20 PY 1996 VL 12 IS 11 BP 1053 EP 1061 DI 10.1089/aid.1996.12.1053 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UZ765 UT WOS:A1996UZ76500012 PM 8827221 ER PT J AU Chapman, J Korczyn, AD Goldfarb, LG AF Chapman, J Korczyn, AD Goldfarb, LG TI Familial Alzheimer's disease associated with S182 codon 286 mutation (vol 346, pg 1040, 1995) SO LANCET LA English DT Correction, Addition C1 NINCDS,NEUROGENET SECT,NIH,BETHESDA,MD. RP Chapman, J (reprint author), TEL AVIV UNIV,SACKLER FAC MED,DEPT NEUROL,IL-69978 RAMAT AVIV,ISRAEL. RI Chapman, Joab/E-4598-2010; Korczyn, Amos/C-3461-2017 OI Korczyn, Amos/0000-0003-0125-2579 NR 2 TC 1 Z9 1 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 20 PY 1996 VL 348 IS 9021 BP 206 EP 206 DI 10.1016/S0140-6736(05)66162-4 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UX789 UT WOS:A1996UX78900070 PM 8691968 ER PT J AU Dunnick, JK Elwell, MR Haseman, JK AF Dunnick, JK Elwell, MR Haseman, JK TI Decreased incidence of spontaneous mammary gland neoplasms in female F344 rats treated with amphetamine, methylphenidate, or codeine (vol 102, pg 77, 1996) SO CANCER LETTERS LA English DT Correction, Addition RP Dunnick, JK (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 19 PY 1996 VL 105 IS 1 BP 121 EP 122 DI 10.1016/0304-3835(96)04335-2 PG 2 WC Oncology SC Oncology GA UV573 UT WOS:A1996UV57300016 ER PT J AU Ogawa, Y Lei, PS Kovac, P AF Ogawa, Y Lei, PS Kovac, P TI Synthesis of four glycosides of a disaccharide fragment representing the terminus of the O-polysaccharide of Vibrio cholerae O:1, serotype Inaba, bearing aglycons suitable for linking to proteins SO CARBOHYDRATE RESEARCH LA English DT Article DE Vibrio cholerae O:1; disaccharide epitope; O-antigen; neoglycoconjugate ID METHYL ALPHA-GLYCOSIDE; 2-(TRIMETHYLSILYL)ETHYL GLYCOSIDES; REPEATING UNIT; ANTIGEN; TRANSFORMATION AB Methyl 4-azido-3-O-benzyl-4,6-dideoxy-alpha-D-mannopyranoside was converted into the crystalline 2-(trimethylsilyl)ethyl 4-azido-2-O-benzoyl-3-O-benzyl-4,6-dideoxy-alpha-D-mannopyranoside. Debenzoylation of the latter, followed by glycosylation of the resulting 2-hydroxy derivative with 2-O-acetyl-4-azido-4,6-dideoxy-alpha-D-mannopyranosyl chloride, gave the 2-(trimethylsilyl)ethyl glycoside of the corresponding disaccharide (8). Deacetylation of 8, followed by reduction of the resulting 4-azido-2-hydroxy derivative with H2S, gave the corresponding amine 10. The latter was treated with 4-O-benzyl-3-deoxy-L-glycero-tetronic acid to give, after debenzylation and acetylation, the fully protected 2-(trimethylsilyl)ethyl alpha-glycoside of the disaccharide fragment of the O-PS of Vibrio cholerae O:1, serotype Inaba (13). Compound 13 was transformed into the corresponding 1-trichloroacetimidate which was treated, separately, with methyl 6-hydroxyhexanoate and 2-(2-methoxycarbonylethylthio)ethanol, to give two analogs of 13 possessing a differing linkage arm, namely the methyl esters 16 and 17, Each of 16 and 17 was treated with aqueous sodium hydroxide, followed by a cation-exchange resin, to give the two corresponding carboxylic acids (19 and 22). Alternately, treatment of 16 and 17 with hydrazine hydrate gave the acid hydrazides 20 and 23. Published by Elsevier Science Ltd. C1 NIDDK,NIH,BETHESDA,MD 20892. NR 21 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUL 19 PY 1996 VL 288 BP 85 EP 98 DI 10.1016/0008-6215(96)00089-4 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA VA459 UT WOS:A1996VA45900007 PM 8765728 ER PT J AU Brzeska, H Korn, ED AF Brzeska, H Korn, ED TI Regulation of class I and class II myosins by heavy chain phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ACTIN-ACTIVATED ATPASE; ACANTHAMOEBA MYOSIN; DICTYOSTELIUM MYOSIN; MG-2+-ATPASE ACTIVITY; SYNTHETIC PEPTIDES; PLASMA-MEMBRANES; BINDING-SITES; KINASE; CASTELLANII; LOCALIZATION C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012 NR 64 TC 77 Z9 77 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 19 PY 1996 VL 271 IS 29 BP 16983 EP 16986 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX943 UT WOS:A1996UX94300001 PM 8707782 ER PT J AU Yoo, SH Lewis, MS AF Yoo, SH Lewis, MS TI Effects of pH and Ca2+ on heterodimer and heterotetramer formation by chromogranin A and chromogranin B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE; INTRACELLULAR STORES; VESICLE MEMBRANE; COIL TRANSITION; CALCIUM RELEASE; PROTEINS; MOBILIZATION; AGGREGATION; ENDOCRINE; SEQUENCE AB The two major proteins of the secretory vesicles of neuroendocrine cells, chromogranin A (CGA) and chromogranin B (CGB), have been shown to undergo pH- and Ca2+-dependent conformational changes and aggregation and have been suggested to play essential roles during secretory vesicle biogenesis in the trans-Gels network, CGA has been shown to exist primarily in a tetrameric state at pH 5.5 and primarily in a dimeric state at pH 7.5, and CGB has been shown to exist in a monomeric state at both pH 5.5 and pH 7.5, Using purified CGA and CGB, it recently has been shown that CGA interacts with CGB at pH 5.5 (Yoo, S, H, (1996) J. Biol, Chem, 271, 1558-1565), In expanding this investigation, we have studied the temperature dependence of the pH-dependent interaction of CGA and CGB by analytical ultracentrifugation and found that two molecules of CGA bound to two molecules of CGB at pH 5.5 with Delta G(0) values of -43.6 kcal/mol in the absence of Ca2+ at 37 degrees C and -40.3 kcal/mol in the presence of 0.1 mM Ca2+, However, one molecule of CGA bound to one molecule of CGB at pH 7.5 with Delta G(0) values of -13.6 kcal/mol in the absence of Ca2+ at 37 degrees C, The magnitude of Delta G(0) values increased with increasing temperatures at both pH values, However, the values for enthalpy and entropy changes decreased with increasing temperatures in both pH levels, suggesting formation of more ordered structures, In the absence of Ca2+ at pH 5,5, the heterotetramerization reaction at 37 degrees C was entropically driven, whereas in the presence of Ca2+ (0.1 mM) the heterotetramerization was virtually an enthalpic reaction, On the other hand, the heterodimer formation in the absence of Ca2+ at pH 7.5 showed large negative enthalpy and entropy changes at 37 degrees C, indicating an enthalpic interaction compensated by entropic changes, In view of the interaction of tetrameric CGA with tetrameric inositol 1,4,5-trisphosphate (Ip(3)) receptor and the existence of heterotetrameric IP3 receptor in the cell, the heterotetramer formation by CGA and CGB not only raises the possibility of interaction between the heterotetrameric chromogranin and heterotetrameric IP3 receptor but also appears to reflect their important roles in the cell. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP Yoo, SH (reprint author), NIDCD,NEUROCHEM LAB,NIH,5 RES COURT,2A37,BETHESDA,MD 20892, USA. NR 31 TC 38 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 19 PY 1996 VL 271 IS 29 BP 17041 EP 17046 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX943 UT WOS:A1996UX94300012 PM 8663344 ER PT J AU Pisegna, JR Wank, SA AF Pisegna, JR Wank, SA TI Cloning and characterization of the signal transduction of four splice variants of the human pituitary adenylate cyclase activating polypeptide receptor - Evidence for dual coupling to adenylate cyclase and phospholipase C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; FUNCTIONAL EXPRESSION; G-PROTEINS; MOLECULAR-CLONING; BINDING-SITES; CELLS; PACAP; NEUROPEPTIDE; BRAIN; GLYCOSYLATION AB Alternative splicing of two exons of the rat pituitary adenylate cyclase activating polypeptide (PACAP) receptor gene generates four major splice variants that are differentially expressed in specific tissues and variably coupled to intracellular second messengers, To evaluate the potential implications of these findings in human physiology, the human PACAP receptor gene was cloned, Alternative splicing about two exons of the gene allowed for four major splice variants that were subsequently identified on cDNA cloning. Each of the four splice variant cDNAs (null, SV-1, SV-2, and SV-3) was stably expressed in NIH/3T3 cells at similar receptor densities. For each splice variant, PACAP (both PACAP-38 and PACAP-27) had similar affinity and potency for stimulating either adenylate cyclase or phospholipase C. However, each receptor splice variant differed in their ligand-stimulated maximal response (efficacy) for total inositol phosphate accumulation with the SV-2 showing the greatest efficacy, followed by the null, SV-1, and SV-3 splice variants. Therefore, unlike the rat, PACAP binds and stimulates signal transduction with nearly equal affinity and potency for each of the receptor splice variants although with varying efficacy for the stimulation of phospholipase C. These results suggest a novel and potentially important mechanism for a single hormone to not only couple to dual signal transduction cascades but also elicit tissue-specific differential activation of phospholipase C in humans. C1 NIDDKD,NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 49 TC 137 Z9 138 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 19 PY 1996 VL 271 IS 29 BP 17267 EP 17274 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX943 UT WOS:A1996UX94300046 PM 8663363 ER PT J AU Pennybacker, M Liessem, B Moczall, H Tifft, CJ Sandhoff, K Proia, RL AF Pennybacker, M Liessem, B Moczall, H Tifft, CJ Sandhoff, K Proia, RL TI Identification of domains in human beta-hexosaminidase that determine substrate specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TAY-SACHS DISEASE; ACTIVATOR PROTEIN; EXTENSIVE HOMOLOGY; EXPRESSION; DEGRADATION; GENES; GM2 AB The lysosomal beta-hexosaminidases are dimers composed of alpha and beta subunits, beta-Hexosaminidase A (alpha beta) is a heterodimer, whereas hexosaminidase B (beta beta) and S (alpha alpha) are homodimers, Although containing a high degree of amino acid identity, each subunit expresses a unique active site that can be distinguished by a differential ability to hydrolyze charged substrates. The site on the beta-subunit primarily degrades neutral substrates, whereas the alpha-subunit site is, in addition, active against sulfated substrates. Isozyme specificity is also exhibited with glycolipid substrates, Among human isozymes, only beta-hexosaminidase A together with the G(M2) activator protein can degrade the natural substrate, G(M2) ganglioside, at physiologically significant rates. To identify the domains of the human beta-hexosaminidase subunits that determine substrate specificity, we have generated chimeric subunits containing both alpha- and beta-subunit sequences, The chimeric constructs were expressed in HeLa cells to screen for activity and then selected constructs were produced in the baculovirus expression system to assess their ability to degrade G(M2) ganglioside in the presence of G(M2) activator protein, Generation of activity against the sulfated substrate required the substitution of two noncontinuous alpha-subunit sequences (amino acids 1-191 and 403-529) into analogous positions of the beta-subunit, Chimeric constructs containing only one of these regions linked to the beta-subunit sequence showed either neutral substrate activity only (amino acids 1-191) or lacked enzyme activity entirely (amino acids 403-529), Neither the chimeras nor the wild-type subunits displayed activator-dependent G(M2)-hydrolyzing activity when expressed alone, However, one chimeric subunit containing alpha amino acids 1-191 fused with beta amino acids 225 to 556, when co-expressed with the wild-type alpha-subunit, showed activity comparable with that of recombinant beta-hexosaminidase A formed by the co-expression of the alpha- and beta subunits. This result indicates that the beta-subunit amino acids 225-556 contribute an essential function in the G(M2)-hydrolyzing activity of beta-hexosaminidase A. C1 NIDDK,SECT BIOCHEM GENET,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. UNIV BONN,INST ORGAN CHEM & BIOCHEM,D-53121 BONN,GERMANY. RI Proia, Richard/A-7908-2012 NR 20 TC 21 Z9 22 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 19 PY 1996 VL 271 IS 29 BP 17377 EP 17382 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX943 UT WOS:A1996UX94300062 PM 8663217 ER PT J AU Kohn, EC Alessandro, R Probst, J Jacobs, W Brilley, E Felder, CC AF Kohn, EC Alessandro, R Probst, J Jacobs, W Brilley, E Felder, CC TI Identification and molecular characterization of a m5 muscarinic receptor in A2058 human melanoma cells - Coupling to inhibition of adenylyl cyclase and stimulation of phospholipase A2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARACHIDONIC-ACID RELEASE; PROTEIN-KINASE-C; A9 L-CELLS; ACETYLCHOLINE-RECEPTOR; CALCIUM INFLUX; PHOSPHOINOSITIDE TURNOVER; INTRACELLULAR CALCIUM; CEREBRAL-CORTEX; MESSENGER-RNAS; CA2+ INFLUX AB We report the identification and biochemical characterization of an endogenous m5 muscarinic acetylcholine receptor (mAChR) in the A2058 human melanoma cell line. This is the first demonstration of a m5AChR outside the central nervous system. The unusual effector coupling of this endogenous m5AChR is presented. The coding region amplified by polymerase chain reaction was identical to the known m5AChR sequence. Binding studies indicated a K-d of 99 +/- 6 pM and a B-max of 45 +/- 4 fmol/mg membrane protein. This m5AChR coupled to stimulation of arachidonic acid release and to a 50% inhibition of forskolin-stimulated cAMP accumulation. The inhibition of cAMP production was insensitive to pertussis toxin treatment, but was dependent upon extracellular calcium. In contrast to the odd mAChR pattern, no cAMP was produced in response 60 carbachol (CC) stimulation. Moreover, no release of inositol phosphates could be measured after CC treatment despite the presence of at least 2 phospholipase C isoforms in A2058 cells. CC-stimulated arachidonic acid release (EC(50) = 17.8 +/- 0.1 mu M) was dependent upon external Ca2+, with marked reduction after coincubation with EGTA, Co2+, Or high doses of verapamil (IC50 = 166 mu M) or diltiazem (IC50 = 243 mu M). Brief exposure to phorbol la-myristate 13-acetate augmented CC-stimulated arachidonic acid release, whereas prolonged phorbol 12-myristate 13-acetate treatment resulted in down-regulation of release. Activation of the m5AChR resulted in Ca2+ influx that was attenuated by muscarinic antagonism and removal of extracellular Ca2+. A2058 cells exposed to CC had no alteration of cell shape or growth potential in monolayer culture, however, a statistically significant reduction in density-independent growth was observed over the range of CC concentrations from 0.1 to 100 mu M. This endogenous m5AChR has a novel signal transduction coupling profile and receptor activation reduces clonogenic potential. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP Kohn, EC (reprint author), NCI,PATHOL LAB,SIGNAL TRANSDUCT & PREVENT UNIT,BLDG 10,RM 2A33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 44 TC 32 Z9 35 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 19 PY 1996 VL 271 IS 29 BP 17476 EP 17484 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX943 UT WOS:A1996UX94300076 PM 8663391 ER PT J AU vanRhee, AM Jiang, JL Melman, N Olah, ME Stiles, GL Jacobson, KA AF vanRhee, AM Jiang, JL Melman, N Olah, ME Stiles, GL Jacobson, KA TI Interaction of 1,4-dihydropyridine and pyridine derivatives with adenosine receptors: Selectivity for A(3) receptors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CENTRAL A(3)-ADENOSINE RECEPTORS; MOLECULAR-CLONING; CALCIUM-CHANNEL; RAT-BRAIN; ANTAGONISTS; BINDING; DIHYDROPYRIDINES; INHIBITION; AFFINITY; CELLS AB 1,4-Dihydropyridine and pyridine derivatives bound to three subtypes of adenosine receptors in the micromolar range. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA [[H-3]-(R)-N-6-(phenylisopropyl)adenosine] and [H-3]CGS 21680 [[H-3]-2-[[4-(2-carboxyethyl)phenyl]ethylamino]-5'-(N-ethylcarbamoyl)adenosine], respectively. Affinity was determined at cloned human and rat A(3) receptors using [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine]. Structure-activity analysis at adenosine receptors indicated that sterically bulky groups at the 4-, 5-, and 6-positions are tolerated. (R,S)-Nicardipine, 12, displayed K-i values of 19.6 and 63.8 mu M at rat A(1) and A(2A) receptors, respectively, and 3.25 mu M at human A(3) receptors. Similarly, (R)-niguldipine, 14, displayed K-i values of 41.3 and 1.90 mu M at A(1) and A(3) receptors, respectively, and was inactive at A(2A) receptors. A preference for the R- vs the S-enantiomer was observed for several dihydropyridines at adenosine receptors, in contrast with the selectivity at L-type Ca2+ channels. A 4-trans-beta-styryl derivative, 24, with a K-i value of 0.670 mu M at A(3) receptors, was 24-fold selective vs A(1) receptors (K-i = 16.1 mu M) and 74-fold vs A(2A) receptors (K-i = 49.3 mu M). The affinity of 24 at L-type Ca2+ channels, measured in rat brain membranes using [H-3]isradipine, indicated a K-i value of 0.694 mu M, and the compound is thus nonselective between A(3) receptors and L-type Ca2+ channels. Inclusion of a 6-phenyl group enhanced A(3) receptor selectivity: Compound 28 (MRS1097; 3,5-diethyl 2-methyl-6-phenyl-4-(trans-2-phenylvinyl)-1,4(R,S)-dihydro-pyridine-3,5-dicarboxylate) was 55-fold selective vs A(1) receptors, 44-fold selective vs A(2A) receptors, and over 1000-fold selective vs L-type Ca2+ channels. In addition, compound 28 attenuated the A(3) agonist-elicited inhibitory effect on adenylylcyclase. Furthermore, whereas nicardipine, 12, displaced radioligand from the Na+-independent adenosine transporter with an apparent affinity of 5.36 +/- 1.51 mu M, compound 28 displaced less than 10% of total binding at a concentration of 100 mu M. Pyridine derivatives, when bearing a 4-alkyl but not a 4-phenyl group, maintained affinity for adenosine receptors. These findings indicate that the dihydropyridines may provide leads for the development of novel, selective A(3) adenosine antagonists. C1 NIDDK,NIH,LBC,MOL RECOGNIT SECT,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 43 TC 81 Z9 81 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 19 PY 1996 VL 39 IS 15 BP 2980 EP 2989 DI 10.1021/jm9600205 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UY270 UT WOS:A1996UY27000014 PM 8709132 ER PT J AU Washburn, RS Jin, DJ Stitt, BL AF Washburn, RS Jin, DJ Stitt, BL TI The mechanism of early transcription termination by Rho026 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcription termination; Rho factor; RNA-binding; NusG; NusD ID CRO MESSENGER-RNA; ATP-BINDING DOMAIN; LAMBDA-PR PROMOTER; ESCHERICHIA-COLI; PHAGE-LAMBDA; DEPENDENT TERMINATION; N-PROTEIN; SITE; NUSG; ANTITERMINATION AB We previously found that nusD-type mutations in Escherichia coli transcription termination factor Rho enhance in vitro transcription termination at four points within the hero gene. Here we show that the early termination points are part of one Rho-dependent termination site, tRE, with properties like those of previously characterized Rho-dependent sites lambda tR1 and trpt'. The early termination points are all RNA polymerase pause sites, and by deletion analysis and oligonucleotide blocking experiments, a common 5' Rho entry site for the early termination points (rutE) is identified. We show that both Rho026 and Rho(+) can use rutE as an entry Feint for termination, but that Rho026 is more efficient in releasing the nascent RNA at tRE. The RNA-dependent ATPase activities of wild-type and mutant Rhos are similar, as are their abilities to bind free RNA and to use (rC)(10) oligomers for ATPase activation. We therefore suggest that Rho-RNA polymerase interactions that define the site of RNA 3' end formation are altered in NusD Rho mutants. NusD Rho mutants are less dependent on, but still responsive to, the transcription termination factor NusG. However, addition of NusG to in vitro termination assays allows Rho(+) to terminate more efficiently at tRE. These results suggest that NusG aids in the 3' end formation process, The decreased dependence on NusG for termination by the mutant Rhos in vitro provides an explanation for poorer lambda growth in rho(nusD) cells by interference with lambda N-mediated antitermination at Rho-dependent sites. (C) 1996 Academic Press Limited C1 TEMPLE UNIV,SCH MED,DEPT BIOCHEM,PHILADELPHIA,PA 19140. NCI,NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [P50-CA12227] NR 48 TC 10 Z9 10 U1 1 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 19 PY 1996 VL 260 IS 3 BP 347 EP 358 DI 10.1006/jmbi.1996.0405 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UY203 UT WOS:A1996UY20300007 PM 8757798 ER PT J AU Capasso, A Guerrini, R Balboni, G Sorrentino, L Temussi, P Lazarus, LH Bryant, SD Salvadori, S AF Capasso, A Guerrini, R Balboni, G Sorrentino, L Temussi, P Lazarus, LH Bryant, SD Salvadori, S TI DMT-TIC-OH, a highly selective and potent delta-opioid dipeptide receptor antagonist after systemic administration in the mouse SO LIFE SCIENCES LA English DT Letter DE Dmt-Tic-OH; opioid dipeptide; antagonism; opioid receptors ID BLOOD-BRAIN-BARRIER; ANALOGS; ANALGESIA; PEPTIDES; MICE AB Dmt-Tic-OH (DTOH) and Dmt-Tic-Ala-OH (DTAOH), effective antagonists in vitro, represent a new potent opioid dipeptides for the delta-opioid receptor (K-i delta of 0.022 nM and a selectivity, K-i mu/K-i delta, of 150,000 for DTOH; K-i delta of 0.285 nM and a selectivity K-i mu/K-i delta, of 20,4 for DTAOH). Ln the present study we considered the pharmacological activity of these two new delta opioid peptide receptor antagonists in vivo. Therefore, we have evaluated their possible antagonistic activity against the antinociception induced by the highly selective delta opioid receptor agonist, [D-Ala(2)]deltorphin II (DEL). Furthermore, these two delta opioid peptide receptor antagonists were injected centrally or peripherally in order to assess their ability to act also after systemic administration. Concurrent i.c.v. injection of DTOH or DTAOH (0.5-1.0-2.0 nM) with DEL (5 nmol) induced a significant reduction of DEL antinociception. By contrast, while DTOH (10-20-40 mg/kg) administered peripherally (i.p., s.c. or i.v.) was also able to reduce DEL antinociception, DTAOH failed. The present results indicate that DTOH is the first opioid dipeptide with delta antagonist activity after systemic administration and it could be important in the clinical and therapeutic applications. C1 UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. UNIV NAPLES FEDERICO II,DEPT EXPTL PHARMACOL,NAPLES,ITALY. UNIV NAPLES FEDERICO II,DEPT CHEM,NAPLES,ITALY. NIEHS,RES TRIANGLE PK,NC 27709. RP Capasso, A (reprint author), UNIV SALERNO,SCH PHARM,PIAZZA VITTORI EMANUELE 9,I-84084 PENTA DI FISCIANO,SALERNO,ITALY. NR 12 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 19 PY 1996 VL 59 IS 8 BP PL93 EP PL98 DI 10.1016/0024-3205(96)00353-0 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UY600 UT WOS:A1996UY60000012 PM 8761022 ER PT J AU Hinnebusch, BJ Perry, RD Schwan, TG AF Hinnebusch, BJ Perry, RD Schwan, TG TI Role of the Yersinia pestis hemin storage (hms) locus in the transmission of plague by fleas SO SCIENCE LA English DT Article ID AGGREGATIVE FIMBRIAE; ESCHERICHIA-COLI; SIPHONAPTERA; FIBRONECTIN; PHENOTYPE; BACILLUS; PROTEINS; DELETION; CUTICLE; BINDING AB Yersinia pestis, the cause of bubonic plague, is transmitted by the bites of infected fleas. Biological transmission of plague depends on blockage of the foregut of the flea by a mass of plague bacilli. Blockage was found to be dependent on the hemin storage (hms) locus. Yersinia pestis hms mutants established long-term infection of the flea's midgut but failed to colonize the proventriculus, the site in the foregut where blockage normally develops. Thus, the hms locus markedly alters the course of Y. pestis infection in its insect vector, leading ro a change in blood-feeding behavior and to efficient transmission of plague. C1 UNIV KENTUCKY,DEPT MICROBIOL & IMMUNOL,LEXINGTON,KY 40536. RP Hinnebusch, BJ (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,NIH,HAMILTON,MT 59840, USA. NR 28 TC 234 Z9 239 U1 0 U2 20 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 19 PY 1996 VL 273 IS 5273 BP 367 EP 370 DI 10.1126/science.273.5273.367 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UY202 UT WOS:A1996UY20200043 PM 8662526 ER PT J AU Piatigorsky, J Horwitz, J AF Piatigorsky, J Horwitz, J TI Characterization and enzyme activity of argininosuccinate lyase/delta-crystallin of the embryonic duck lens SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE delta-crystallin; enzyme activity; enzyme-crystallin; argininosuccinate lyase; (duck embryo); (eye); (lens) ID X-RAY ANALYSIS; DELTA-CRYSTALLIN; LYASE ACTIVITY; NONLENS TISSUES; CHICK LENS; GENE; EXPRESSION; SEQUENCE; RECRUITMENT; PROTEINS AB Argininosuccinate lyase (ASL)/delta-crystallin, a major soluble protein of the transparent eye lens of birds and reptiles, is a mixture of tetramers comprising all possible combinations of two similar polypeptides (delta 1 and delta 2). Only the delta 2 polypeptide has ASL activity. In the present investgation we have purified each of the 5 major isoforms (delta A to delta E, pI 5.2 to 5.8) of delta-crystallin tetramers from the embryonic duck lens by isoelectric focussing and established by peptide sequencing that the delta 1 and delta 2 polypeptides are encoded in the previously identified, linked delta 1 and delta 2 genes, respectively. The relative amounts of the different tetramers in the 14-day-old embryonic lens were consistent with equal expression of the 2 delta-crystallin genes and no preference for assembly of the 2 delta polypeptides. The relative amount of ASL activity of the tetramers was a linear function of the relative amount of their delta 2 polypeptides, with delta A (only delta 1) lacking enzymatic activity altogether. delta B (3 delta 1:1 delta 2), delta C (2 delta 1:2. delta 2), delta D (1 delta 1:3 delta 2) and delta E (4 delta 2) all gave normal Michaelis-Menten kinetics for fumarate production from argininosuccinate at 40 degrees C and had a similar K-m (average K-m for mixture was 0.15 mM). delta E had a K-m of 0.187 mM and a V-max of 9 mu mol/min per mg protein. Unlike bovine and like human ASL, both reported previously, embryonic duck ASL/delta-crystallin showed no evidence of cooperativity or activation by GTP. Each isoform had a similar far ultraviolet circular dichroism spectrum and thermal stability between 20 degrees C and 60 degrees C, with denturation occurring at 65 degrees C. Our data suggest that gene duplication, structural modifications leading to greater thermal stability of the delta 1 and delta 2 polypeptides, and selective loss of ASL activity in the delta 1 polypeptide all occurred during the recruitment of ASL for a refractive role in the duck lens, resulting in the generation of ASL isoenzymes. RP NEI, MOLEC & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 52 TC 21 Z9 21 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD JUL 18 PY 1996 VL 1295 IS 2 BP 158 EP 164 DI 10.1016/0167-4838(96)00030-1 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UY024 UT WOS:A1996UY02400005 PM 8695641 ER PT J AU Johansson, HJ Jagersten, C Shiloach, J AF Johansson, HJ Jagersten, C Shiloach, J TI Large scale recovery and purification of periplasmic recombinant protein from E-coli using expanded bed adsorption chromatography followed by new ion exchange media SO JOURNAL OF BIOTECHNOLOGY LA English DT Article DE expanded bed; exotoxin A; capture; chromatography ID AERUGINOSA EXOTOXIN-A; ESCHERICHIA-COLI AB Expanded bed chromatography was used for the recovery and purification of modified Pseudomonas aeruginosa exotoxin A. The exotoxin accumulates in the periplasmic space of E. coli BL21(lambda DE3), was released from the cells by osmotic shock and captured by applying the open cell suspension directly to an anion exchanger (STREAMLINE(TM) DEAE) using an expanded bed (STREAMLINE(R)) column. Processing of 4.5 kg of E. coli using the expanded bed process was 3 times faster and did not require clarification of the bacterial extract, in comparison with the conventional purification method. Also, the recovered protein solution was 3 times more concentrated and the yield slightly higher. C1 PHARM BIOTECH AB,S-75182 UPPSALA,SWEDEN. NIDDK,BIOTECHNOL UNIT,NIH,BETHESDA,MD 20892. NR 8 TC 57 Z9 59 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1656 J9 J BIOTECHNOL JI J. Biotechnol. PD JUL 18 PY 1996 VL 48 IS 1-2 BP 9 EP 14 DI 10.1016/0168-1656(96)01390-9 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VG927 UT WOS:A1996VG92700002 PM 8818269 ER PT J AU Hagen, SJ Hofrichter, J Eaton, WA AF Hagen, SJ Hofrichter, J Eaton, WA TI Geminate rebinding and conformational dynamics of myoglobin embedded in a glass at room temperature SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID BARRIER HEIGHT DISTRIBUTIONS; LIGAND-BINDING; HEME-PROTEINS; NEUTRON-SCATTERING; RELAXATION DYNAMICS; SOLVENT VISCOSITY; CO BINDING; HEMOGLOBIN; RECOMBINATION; SPECTROSCOPY AB Below the glycerol/water glass transition (similar to 180 K), myoglobin exhibits distributed geminate rebinding kinetics as a result of ''frozen'' conformational substates (Austin et al. Biochemistry 1975, 14, 5355). As the temperature is increased through the solvent glass transition, the apparent rate of geminate rebinding decreases. This slowing has been attributed to a protein relaxation that impedes CO rebinding at high T, but that is itself prevented at low T by energetic barriers to conformational change (Steinbach et al. Biochemistry 1991, 30, 3955). Using time-resolved spectroscopy with nanosecond lasers, we have studied ligand rebinding in sperm whale MbCO embedded in a glass at room temperature, Over a wide temperature range T = 105-297 K, the kinetics of rebinding are well characterized by the same inhomogeneous distribution g(H-BA) of enthalpy barriers H-BA, and changes in the shape of the Soret difference spectrum during rebinding can be explained by ''kinetic hole burning''. That is, at sufficiently high viscosity the multiexponential ''low temperature'' rebinding of MbCO can be observed at all T, as predicted by Ansari et al. (Science 1992, 256, 1796). Moreover, the average geminate rate predicted from the observed rate distribution is similar to 2500 times larger than the geminate rate in the completely relaxed protein in aqueous solution (Ansari et al Biochemistry 1994, 33, 5128). Thus, we have shown that high solvent viscosity prevents both interconversion of conformational substates and functionally important relaxation in the interior of the protein, independent of T. C1 NIH,CHEM PHYS LAB,BETHESDA,MD 20892. NR 62 TC 87 Z9 87 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JUL 18 PY 1996 VL 100 IS 29 BP 12008 EP 12021 DI 10.1021/jp960219t PG 14 WC Chemistry, Physical SC Chemistry GA UX961 UT WOS:A1996UX96100026 ER PT J AU Schuebel, KE Bustelo, XR Nielsen, DA Song, BJ Barbacid, M Goldman, D Lee, IJ AF Schuebel, KE Bustelo, XR Nielsen, DA Song, BJ Barbacid, M Goldman, D Lee, IJ TI Isolation and characterization of murine vav2, a member of the vav family of proto-oncogenes SO ONCOGENE LA English DT Article DE proto-oncogene; signal transduction; gene expression ID GUANINE-NUCLEOTIDE EXCHANGE; TYROSINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; T-CELL; HEMATOPOIETIC-CELLS; SIGNALING PATHWAY; SH2 DOMAIN; BINDING PROTEINS; POINT MUTATIONS; STEEL FACTOR AB We describe the isolation and characterization of a cDNA encoding murine vav2. vav2 shares 63% and 55% identity at the nucleic acid and amino acid levels, respectively, with vav, a proto-oncogene that plays an essential role in embryonic development and hematopoietic signal transduction. The 100 kDa Vav2 protein contains the characteristic array of structural motifs found in Vav. However, unlike vav, vav2 transcripts are widely distributed in both hematopoietic and nonhematopoietic tissues. In the adult, vav2 mRNA is found at high levels in the spleen, liver, testes and placenta. Northern blot analysis reveals two vav2 mRNA species (designated alpha and beta). The alpha species is expressed throughout development while the alpha and beta species are expressed tissue-specifically in adults. Transfection of NIH3T3 cells with expression vectors containing vav2 deletions demonstrate that elimination of 183 amino terminal residues of Vav2 is sufficient to activate its oncogenic potential. Vav2-induced transformation is characterized by the appearance of foci composed of cells in which cytokinesis and karyokinesis are uncoupled. This phenotype is comparable, but not identical, to morphological changes induced by Vav and other members of the Dbl family of oncoproteins. Our results suggest that Vav family members mediate functions important in the regulation of cell architecture and proliferation in most, if not all, tissues. C1 NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOL BIOL,PRINCETON,NJ 08543. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 51 TC 100 Z9 102 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 18 PY 1996 VL 13 IS 2 BP 363 EP 371 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VA252 UT WOS:A1996VA25200015 PM 8710375 ER PT J AU Wachholz, BW AF Wachholz, BW TI Thyroid cancers in children in Belarus SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP Wachholz, BW (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 17 PY 1996 VL 88 IS 14 BP 946 EP 946 DI 10.1093/jnci/88.14.946 PG 1 WC Oncology SC Oncology GA UX127 UT WOS:A1996UX12700005 ER PT J AU Wang, QZ Fan, SJ Eastman, A Worland, PJ Sausville, EA OConnor, PM AF Wang, QZ Fan, SJ Eastman, A Worland, PJ Sausville, EA OConnor, PM TI UCN-01, a potent abrogator of G(2) checkpoint function in cancer cells with disrupted p53 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROTEIN-KINASE-C; SELECTIVE INHIBITOR; ANTITUMOR-ACTIVITY; CYCLE CHECKPOINTS; NITROGEN-MUSTARD; DNA DAMAGE; BHK CELLS; STAUROSPORINE; ACTIVATION; DEPHOSPHORYLATION AB Background: Arrest of the cell cycle in G(2) phase following DNA damage helps protect cell viability by allowing time for DNA repair before entry into mitosis (M phase), Abrogation of G(2) arrest sensitizes cells to the effects of DNA-damaging agents, UCN-01 (7-hydroxystaurosporine), a protein kinase C inhibitor that may block G(2) checkpoint regulation, has been reported to enhance the cytotoxicity of mitomycin C, a known DNA-damaging agent, Purpose: We studied the effect of UCN-01 on G(2) checkpoint control in human lymphoma CA46 cells, whose sensitivity to various DNA-damaging agents and G(2) response to DNA damage have been characterized, We also assessed the ability of UCN-01 to enhance the cytotoxicity of gamma irradiation in CA46 cells and human colon carcinoma HT-29 cells, both of which are mutant for p53 function, The influence of p53 function on UCN-01-mediated abrogation of the G(2) checkpoint and enhancement of DNA-damaging agent cytotoxicity was studied in transfected human breast carcinoma MCF-7 cells that either expressed or did not express the human papillomavirus type-16 E6 protein, MCF-7 cells have normal p53 function, and the E6 protein binds p53 protein and promotes its destruction. Methods: The effect of UCN-01 on cell cycle arrest induced by gamma irradiation was studied in CA46 cells and in transfected MCF-7 cells by use of flow cytometry, A histone H1 phosphorylation assay was employed to measure cyclin B1/Cdc2 kinase activity in extracts derived from irradiated and nonirradiated CA46 cells that had been either treated or not treated with UCN-01; the phosphorylation status of Cdc2 kinase protein in the same extracts was determined by use of western blotting, The effect of UCN-01 on the cytotoxicity of gamma irradiation in CA46 and HT-29 cells was determined by use of MTT (thiazolyl blue) and clonogenic (colony-forming) assays, respectively; a clonogenic assay was also used to measure the effect of UCN-01 on the cytotoxicity of cisplatin in transfected and nontransfected MCF-7 cells, Results: G(2) arrest induced in CA46 cells by gamma irradiation was inhibited by treatment with UCN-01 in a dose-dependent manner; arrest in G(2) was completely abrogated by exposure to 300 nM UCN-01. Biochemical markers indicative of the G(2)/M transition, including the activation of cyclin B1/Cdc2 kinase and the suppression of Cdc2 threonine-14 and tyrosine-15 phosphorylation, were detected in irradiated cells treated with UCN-01, UCN-01 enhanced the cytotoxicity of gamma irradiation in CA46 and HT-29 cells, MCF-7 cells with functional p53 protein were more resistant to G(2) checkpoint abrogation by UCN-01 than MCF-7 cells with disrupted p53 function, UCN-01 markedly enhanced the cell-killing activity of cisplatin in MCF-7 cells defective for p53 function, Conclusions and Implications: UCN-01 is a potent abrogator of G(2) checkpoint control in cancer cells with disrupted p53 function, UCN-01 might be capable of enhancing the effectiveness of DNA-damaging agents in the treatment of tumors with cells lacking normal p53 function. C1 NCI,DIV BASIC SCI,MOLEC PHARMACOL LAB,NIH,BETHESDA,MD 20892. NCI,DIV BASIC SCI,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. DARTMOUTH COLL SCH MED,DEPT PHARMACOL,HANOVER,NH. NR 43 TC 335 Z9 350 U1 0 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 17 PY 1996 VL 88 IS 14 BP 956 EP 965 DI 10.1093/jnci/88.14.956 PG 10 WC Oncology SC Oncology GA UX127 UT WOS:A1996UX12700010 PM 8667426 ER PT J AU Talaska, G Cudnik, J Jaeger, M Rothman, N Hayes, R Bhatnagar, VJ Kayshup, SJ AF Talaska, G Cudnik, J Jaeger, M Rothman, N Hayes, R Bhatnagar, VJ Kayshup, SJ TI Development and application of non-invasive biomarkers for carcinogen-DNA adduct analysis in occupationally exposed populations SO TOXICOLOGY LA English DT Article; Proceedings Paper CT Conference on Risk Assessment Issues for Sensitive Human Populations CY APR 25-27, 1995 CL DAYTON, OH SP Tri Serv Toxicol, Wright Patterson Air Force Base, US EPA, Off Res & Dev, ATSDR, Div Toxicol DE non-invasive biomarkers; carcinogen-DNA adduct analysis; occupational hazards; exposure/effect assessment; monitoring technique ID POLYCYCLIC AROMATIC-HYDROCARBONS; EXFOLIATED UROTHELIAL CELLS; URINARY-BLADDER; SMOKING; MICE; SKIN; DOGS AB Biological monitoring of exposures to carcinogenic compounds in the workplace can be a valuable adjunct to environmental sampling and occupational medicine. Carcinogen-DNA adduct analysis has promise as a biomarker of effective dose if target organ samples can be obtained non-invasively. We have developed non-invasive techniques using exfoliated urothelial and bronchial cells collected in urine and sputum, respectively. First morning urine samples were collected from 33 workers exposed to benzidine or benzidine-based dyes and controls matched for age, education, and smoking status. Sufficient DNA for P-32-postlabelling analysis was obtained from every sample. Mean levels of a specific DNA adduct (which co-chromatographed with standard characterized by MS) were elevated significantly in the benzidine-exposed workers relative to controls, In addition, workers exposed to benzidine had higher adduct levels than those exposed to benzidine-based dyes. This study demonstrates the usefulness of these non-invasive techniques for exposure/effect assessment. To be useful in occupational studies, biomarkers must also be sensitive to exposure interventions. We have conducted topical application studies of used gasoline engine oils in mice and found that the levels of carcinogen-DNA adducts in skin and lung can be significantly lowered if skin cleaning is conducted in a timely manner. The combination of useful, non-invasive techniques to monitor exposure and effect and industrial hygiene interventions can be used to detect and prevent exposures to a wide range of carcinogens including those found in used gasoline engine oils and jet exhausts. C1 NCI, ENVIRONM EPIDEMIOL BRANCH, OCCUPAT STUDIES SECT, BETHESDA, MD 20892 USA. NATL INST OCCUPAT HLTH, AMEMBABAD, INDIA. RP Talaska, G (reprint author), UNIV CINCINNATI, DEPT ENVIRONM HLTH, CINCINNATI, OH 45267 USA. NR 17 TC 15 Z9 15 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 17 PY 1996 VL 111 IS 1-3 BP 207 EP 212 DI 10.1016/0300-483X(96)03377-X PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VB148 UT WOS:A1996VB14800018 PM 8711736 ER PT J AU Kruk, PA Balajee, AS Rao, KS Bohr, VA AF Kruk, PA Balajee, AS Rao, KS Bohr, VA TI Telomere reduction and telomerase inactivation during neuronal cell differentiation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN FIBROBLASTS AB Telomerase adds (TTAGGG)(n) hexanucleotide repeats to the ends of mammalian telomeres. This compensates for telomeric loss with successive rounds of cellular replication. Telomerase activity is detected in many neoplastic cells, but not in most normal somatic cells. To determine whether telomeric length and telomerase activity are associated with cellular differentiation, we measured telomeric lengths and telomerase activity in embryonic NT2 precursor cells prior to and following differentiation into post mitotic hNT neurons. This system allows for studies in a direct neuronal cell lineage and, thus, provides a unique model for studying the role of neuronal telomerase activity. Our results show that telomerase activity was present in precursor cells, but not in neuronal cells. Telomeres were consistently longer in NT2 cells than in hNT cells. These results suggest that changes in telomeric length and loss of telomerase activity play a role in neuronal cellular differentiation. (C) 1996 Academic Press, Inc. C1 UNIV HYDERABAD,DEPT BIOCHEM,HYDERABAD 500046,ANDHRA PRADESH,INDIA. RP Kruk, PA (reprint author), NIA,MOLEC GENET LAB,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Kruk, Patricia/I-6489-2012 NR 17 TC 45 Z9 47 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 16 PY 1996 VL 224 IS 2 BP 487 EP 492 DI 10.1006/bbrc.1996.1054 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UY656 UT WOS:A1996UY65600033 PM 8702416 ER PT J AU Schwab, JM Smith, JL Leesong, M Sathyanarayana, BK AF Schwab, JM Smith, JL Leesong, M Sathyanarayana, BK TI Reevaluation of the link between enzyme mechanism and reaction stereochemistry for a dehydratase-allylic isomerase. SO BIOCHEMISTRY LA English DT Meeting Abstract C1 PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. PURDUE UNIV,DEPT SCI BIOL,W LAFAYETTE,IN 47907. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 16 PY 1996 VL 35 IS 28 BP 37 EP 37 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX738 UT WOS:A1996UX73800070 ER PT J AU Klausner, RD AF Klausner, RD TI Exploring the biology of transition metals. SO BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 16 PY 1996 VL 35 IS 28 BP 94 EP 94 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX738 UT WOS:A1996UX73800126 ER PT J AU Mukhopadhyay, AK Dracheva, S Bose, S Hendler, RW AF Mukhopadhyay, AK Dracheva, S Bose, S Hendler, RW TI Control of the integral membrane proton pump, bacteriorhodopsin, by purple membrane lipids of Halobacterium halobium SO BIOCHEMISTRY LA English DT Article ID POLAR LIPIDS; PHOTOCYCLE AB Brief exposure of purple membrane (PM) to dilute Triton X-100 eliminates the actinic light effect on the relative amounts of fast M (Mf) and slow M (M,) intermediates and alters the character and kinetics of the photocycle, without destroying the native BR trimers (Mukhopadhyay et al., 1994). Particular membrane lipids are removed during the Triton treatment, and adding back an extract of membrane lipids can repair most of the affected photocycle behavior (Dracheva et al., 1996). This paper defines conditions which are important in the reconstitution procedure, using a group of quantitative parameters which measure the extents of damage and repair. Circular dichroism in both the UV and visible ranges shows that Triton can disturb both the secondary structure of BR and its ability to polymerize into trimers. Whereas the damage to protein conformation could be reversed by lipids alone, the formation of trimers and recovery of normal photocycle behavior required both lipids and a high salt concentration. C1 NHLBI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. NR 19 TC 37 Z9 37 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 16 PY 1996 VL 35 IS 28 BP 9245 EP 9252 DI 10.1021/bi960738m PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX738 UT WOS:A1996UX73800029 PM 8703930 ER PT J AU Morens, DM White, LR Davis, JW AF Morens, DM White, LR Davis, JW TI The frequency of idiopathic Parkinson's disease by age, ethnic group, and sex in northern Manhattan, 1988-1993 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 UNIV HAWAII,SCH PUBL HLTH,DEPT TROP MED,HONOLULU,HI 96822. UNIV HAWAII,SCH MED,DEPT PUBL HLTH SCI,HONOLULU,HI 96822. UNIV HAWAII,SCH MED,DEPT TROP MED,HONOLULU,HI 96822. NIA,NIH,HONOLULU,HI 96817. HAWAII OSTEOPOROSIS CTR,HONOLULU,HI 96814. RP Morens, DM (reprint author), UNIV HAWAII,SCH PUBL HLTH,DEPT PUBL HLTH SCI,HONOLULU,HI 96822, USA. NR 4 TC 1 Z9 1 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 15 PY 1996 VL 144 IS 2 BP 198 EP 198 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UW801 UT WOS:A1996UW80100013 PM 8678053 ER PT J AU Parker, CE Papac, DI Tomer, KB AF Parker, CE Papac, DI Tomer, KB TI Monitoring cleavage of fusion proteins by matrix-assisted laser desorption ionization mass spectrometry: Recombinant HIV-1 (IIIB) p26 SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; PROTEOLYSIS AB Matrix-associated laser desorption ionization/mass spectrometry (MALDI/MS) has been used to examine whole bacteria for the presence of a recombinant HIV p26 fusion protein. MALDI/MS, combined with affinity-purification techniques, is also shown to be very useful in monitoring the enzymatic cleavage of both affinity-bound fusion protein and fusion protein in solution. The combination of mass resolution, sensitivity, and speed of analysis makes MALDI/MS an attractive alternative to SDS-PAGE. (C) 1995 Academic Press, Inc. C1 NIEHS,MOL BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 21 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 15 PY 1996 VL 239 IS 1 BP 25 EP 34 DI 10.1006/abio.1996.0286 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UY648 UT WOS:A1996UY64800004 PM 8660621 ER PT J AU Masur, H Whitcup, SM Cartwright, C Polis, M Nussenblatt, R AF Masur, H Whitcup, SM Cartwright, C Polis, M Nussenblatt, R TI Advances in the management of AIDS-related cytomegalovirus retinitis SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID IMMUNE-DEFICIENCY-SYNDROME; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; POLYMERASE CHAIN-REACTION; PERIPHERAL-BLOOD LEUKOCYTES; OCULAR MANIFESTATIONS; RETINAL DETACHMENTS; VIRUS INFECTION; GANCICLOVIR; FOSCARNET; DISEASE C1 NEI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. JOHNSON & JOHNSON CLIN DIAGNOST,NUCLE ACIDS DIV,ROCHESTER,NY 14650. RP Masur, H (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,BETHESDA,MD 20892, USA. OI Polis, Michael/0000-0002-9151-2268 NR 69 TC 50 Z9 51 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 1996 VL 125 IS 2 BP 126 EP 136 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA UV921 UT WOS:A1996UV92100011 PM 8678367 ER PT J AU Conconi, M Szweda, LI Levine, RL Stadtman, ER Friguet, B AF Conconi, M Szweda, LI Levine, RL Stadtman, ER Friguet, B TI Age-related decline of rat liver multicatalytic proteinase activity and protection from oxidative inactivation by heat-shock protein 90 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE aging; multicatalytic proteinase; rat liver; oxidative inactivation; heat shock protein 90 ID GLUTAMINE-SYNTHETASE; OXIDIZED PROTEINS; COMPLEX; DEGRADATION; PROTEOLYSIS; PROTEASES; BRAIN; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; ELECTROPHORESIS; PURIFICATION AB To test whether an observed age-related increase in the level of oxidized protein in rat liver is due to a decrease in the activity of the multicatalytic proteinase (MCP), this protease was isolated from liver of young (8-month-old) and old (24-month-old) male Fischer 344 rats. Three peptidase activities of the MCP were assayed using fluorogenic peptides: trypsin-like, chymotrypsin-like, and peptidylglutamyl-peptide hydrolase, Only peptidylglutamyl-peptide hydrolase activity declined with age, with protease from old animals exhibiting approximately 50% of the activity of that from young animals, Bidimensional gel electrophoresis and thermostability studies did not reveal age-related structural modifications of the MCP subunits. Peptidylglutamyl-peptide hydrolase activity and trypsin-like activity were sensitive to metal-catalyzed oxidation. In some preparations, a 95-kDa protein that has been identified as the heat shock protein 90 copurified with the MCP, In the presence of HSP 90, trypsin-like activity is protected from oxidative inactivation and chymotrypsin-like activity is slightly activated. Peptidylglutamyl-peptide hydrolase activity remained sensitive to oxidation in protease isolated from young rats, but that from old rats was resistant to oxidative inactivation, Furthermore, addition of rat HSP 90 to rat liver MCP (purified from 8-month-old animals and free of contaminating HSP 90) was found to protect trypsin-like activity from oxidative inactivation. (C) 1996 Academic Press, Inc. C1 INST PASTEUR,UNITE BIOCHIM CELLULAIRE,F-75724 PARIS 15,FRANCE. CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,CLEVELAND,OH 44106. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RI Levine, Rodney/D-9885-2011 NR 43 TC 166 Z9 168 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 15 PY 1996 VL 331 IS 2 BP 232 EP 240 DI 10.1006/abbi.1996.0303 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UX874 UT WOS:A1996UX87400010 PM 8660703 ER PT J AU Wink, DA Cook, JA Pacelli, R DeGraff, W Gamson, J Liebmann, J Krishna, MC Mitchell, JB AF Wink, DA Cook, JA Pacelli, R DeGraff, W Gamson, J Liebmann, J Krishna, MC Mitchell, JB TI The effect of various nitric oxide-donor agents on hydrogen peroxide-mediated toxicity: A direct correlation between nitric oxide formation and protection SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID NUCLEOPHILE COMPLEXES; ISCHEMIA-REPERFUSION; MYOCARDIAL-ISCHEMIA; NITROSYL HYDRIDE; RELEASE; CELLS; NO; NITROPRUSSIDE; ACTIVATION; OXIDATION AB The role that nitric oxide (NO) plays in various degenerative and disease states has remained a mystery since its discovery as a biological messenger, prompting the question, ''NO, friend or foe?'' Some reports have suggested that NO is cytotoxic, and yet others have shown that it possesses protective properties against reactive oxygen species (ROS). Many studies have used various NO donor complexes arriving at seemingly different conclusions. This report will address the effects of various NO donor compounds on ROS-mediated toxicity. Consistent with our previous study, the NO donor compound, DEA/NO ((C2H5)(2)N[N(O)NO]Na--+), afforded protection against hydrogen peroxide-mediated cytotoxicity in V79 Chinese hamster lung fibroblasts at concentrations as low as 10 mu M DEA/NO. Furthermore, a survey of other NO donor complexes revealed that some either protected or potentiated hydrogen peroxide-mediated cytotoxicity. 3-Morpholinosynodiomine(.)HCl (SIN-1) and sodium nitroprusside (SNP) enhanced hydrogen peroxide-mediated cytotoxicity, while S-nitrosoglutathione (GSNO), and S-nitroso-N-acetylpenicillamine (SNAP) afforded protection. Electrochemical detection of NO in cell culture medium revealed that neither 1000 mu M SIN-1 nor SNP yielded appreciable NO concentrations (<0.3 mu M). In contrast, DEA/NO, SNAP, and GSNO yielded fluxes of NO >1.0 mu M. Thus, a direct correlation between inhibition of hydrogen peroxide cytotoxicity and NO production was observed: agents that release NO during hydrogen peroxide treatment afford significant protection, whereas agents that do not release NO do not protect. Similar results were observed for NO donors studied when hypoxanthine/xanthine oxidase was used as the source for ROS, although the S-nitrosothiol agents were much less protective. These results demonstrate that NO possesses properties which protect against ROS toxicity and demonstrate how the use of different NO donor compounds can lead to different conclusions about the role that NO can play in the cytotoxicity of ROS. (C) 1996 Academic Press, Inc. RP Wink, DA (reprint author), NCI,RADIAT BIOL BRANCH,TUMOR BIOL SECT,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892, USA. NR 49 TC 178 Z9 181 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 15 PY 1996 VL 331 IS 2 BP 241 EP 248 DI 10.1006/abbi.1996.0304 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UX874 UT WOS:A1996UX87400011 PM 8660704 ER PT J AU Berrettini, WH Persico, AM AF Berrettini, WH Persico, AM TI Dopamine D2 receptor gene polymorphisms and vulnerability to substance abuse in African Americans SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dopamine receptor; alcoholism; genetics ID ALLELIC ASSOCIATION; SEVERE ALCOHOLISM; AL ALLELE; RFLP; LOCUS; POPULATION; DRD2; DNA C1 THOMAS JEFFERSON UNIV,DEPT PSYCHIAT,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT PHARMACOL,PHILADELPHIA,PA 19107. NIDA,MOL NEUROBIOL BRANCH,ADDICT RES CTR,NIH,BALTIMORE,MD 21224. NR 29 TC 31 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 1996 VL 40 IS 2 BP 144 EP 147 DI 10.1016/0006-3223(96)00036-4 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UT234 UT WOS:A1996UT23400007 PM 8793046 ER PT J AU Keuler, DJ Altemus, M Michelson, D Greenberg, B Murphy, DL AF Keuler, DJ Altemus, M Michelson, D Greenberg, B Murphy, DL TI Behavioral effects of naloxone infusion in obsessive-compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE naloxone; obsessive-compulsive disorder; anxiety; behavioral effects ID PAIN C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,DIV INTRAMURAL RES PROGRAMS,BETHESDA,MD 20892. RP Keuler, DJ (reprint author), NIMH,CLIN SCI LAB,DIV INTRAMURAL RES PROGRAMS,BLDG 10,ROOM 3D41,10 CTR DR MSC 1264,BETHESDA,MD 20892, USA. NR 11 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 15 PY 1996 VL 40 IS 2 BP 154 EP 156 DI 10.1016/0006-3223(95)00632-X PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UT234 UT WOS:A1996UT23400010 PM 8793049 ER PT J AU Nelson, EL Li, XB Hsu, FJ Kwak, LW Levy, R Clayberger, C Krensky, AM AF Nelson, EL Li, XB Hsu, FJ Kwak, LW Levy, R Clayberger, C Krensky, AM TI Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin's lymphoma SO BLOOD LA English DT Article ID ACTIVE SPECIFIC IMMUNOTHERAPY; IMMUNOGLOBULIN; ANTIBODY; MELANOMA; ANTIGEN; INDUCTION; IMMUNOGENICITY; LEUKEMIA; IMMUNITY; PROTEIN AB Patients with non-Hodgkin's B-cell lymphoma who received an antitumor vaccine lg idiotypic lg protein showed humoral and proliferative immune responses. Because immunity to some antigens, including tumor antigens and human pathogenic viruses, may be better correlated with the cytolytic cellular immune response, we evaluated 16 non-Hodgkin's lymphoma patients immunized with autologous idiotypic lg molecules for changes in tumor-specific cytotoxic T-lymphocyte precursor (CTLp) frequency using limiting dilution analysis. Eleven patients had a significant increase in tumor-specific CTLp, Eight of these 11 patients remain without evidence of disease or with stable minimal disease, In contrast, all five patients who did not have a significant change in tumor-specific CTLp have developed progressive disease, Patient vaccination with tumor-associated protein antigens can increase tumor-specific CTLp frequencies. The correlation of increased tumor-specific CTLp with freedom from progression is significant at P = .002, This study indicates that measurement of CTLp frequencies are relevant to the clinical evaluation of human tumor vaccines and suggests that cell-mediated cytolytic immune responses may be an important determinant of vaccine efficacy. (C) 1996 by The American Society of Hematology. C1 NCI,CLIN RES BRANCH,FREDERICK,MD 21701. STANFORD UNIV,SCH MED,DEPT MED,DIV ONCOL,STANFORD,CA 94305. STANFORD UNIV,SCH MED,DEPT CARDIOTHORAC SURG,STANFORD,CA 94305. STANFORD UNIV,SCH MED,DEPT PEDIAT,DIV IMMUNOL & TRANSPLANTAT BIOL,STANFORD,CA 94305. NCI,CLIN RES BRANCH,FREDERICK,MD 21701. RI Krensky, Alan/F-7956-2011 FU NCI NIH HHS [CA33399, CA34233, CA34639] NR 84 TC 103 Z9 104 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1996 VL 88 IS 2 BP 580 EP 589 PG 10 WC Hematology SC Hematology GA UW488 UT WOS:A1996UW48800023 PM 8695806 ER PT J AU Greiner, TC Gascoyne, RD Anderson, ME Kingma, DW Adomat, SA Said, J Jaffe, ES AF Greiner, TC Gascoyne, RD Anderson, ME Kingma, DW Adomat, SA Said, J Jaffe, ES TI Nodular lymphocyte-predominant Hodgkin's disease associated with large-cell lymphoma: Analysis of Ig gene rearrangements by V-J polymerase chain reaction SO BLOOD LA English DT Article ID REED-STERNBERG CELLS; ANTIGEN RECEPTOR GENES; B-CELL; COMPOSITE LYMPHOMA; GERMINAL-CENTERS; AMPLIFIED DNA; IMMUNOGLOBULIN; PARAGRANULOMA; IDENTIFICATION; DIAGNOSIS AB The clonality of nodular lymphocyte-predominant Hodgkin's disease (NLPHD) and the relationship to composite or sequential large-cell lymphomas (LCLs) is poorly understood. Clonal Ig heavy-chain gene rearrangements (IgHGR) have infrequently been observed in NLPHD by Southern hybridization. The goals of this study were (1) to determine if IgHGR could be identified by polymerase chain reaction (PCR) techniques in the LCL associated with NLPHD; (2) to determine if the IgHGR identified in the LCL could also be found in the associated NLPHD; and (3) to determine if Epstein-Barr virus (EBV) played a role a role in histologic progression to LCL. Using consensus primers to conserved regions in the IgH variable (V) and joining (J) region genes, we analyzed formalin-fixed paraffin-embedded sections from the biopsies of 25 patients referred to the National Cancer Institute (NCI) registry for NLPHD and LCL using both single-step and seminested V-J PCR. The histologically aggressive component was further subclassified as frank LCL or as L&H-cell-rich, but not fulfilling criteria for LCL. Matched samples representing both NLPHD and aggressive components were available in 13 cases. In 12 cases, only one component was available (aggressive, n = 8; NLPHD, n = 4). In addition, we also amplified, with P-32 labeling, 12 cases of NLPHD without associated LCL, Two clonal IgHGR were identified in 29 cases (7%) of typical NLPHD, both of which were associated with LCL containing a similar sized band by PCR. The clonal identity of the bands in the NLPHD and associated LCL was confirmed by sequencing the products in these two cases. Eight of 10 cases (80%) of LCL associated with NLPHD contained a clonal band by this technique. By contrast, none of the cases classified as L&H-cell-rich contained an IgHGR. The single-step and seminested PCR methods produced identical results. All clonal LCLs were studied for EBV sequences by in situ hybridization using the EBER1 probe, and were negative. We conclude that the LCLs associated with NLPHD are clonal B-cell malignancies. However, by these methods, the same clone can be identified in only a minority of cases of NLPHD and LCL. EBV does not appear to play a role in histologic progression. Moreover, our results suggest that many cases suspected of being LCL may actually represent NLPHD with increased numbers of L&H cells. In histologically equivocal cases, the diagnosis of LCL should be reserved for those cases in which a clonal B-cell neoplasm can be demonstrated. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,NATL INST HLTH,BETHESDA,MD 20892. BRITISH COLUMBIA CANC AGCY,VANCOUVER,BC V5Z 4E6,CANADA. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. NR 56 TC 55 Z9 63 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1996 VL 88 IS 2 BP 657 EP 666 PG 10 WC Hematology SC Hematology GA UW488 UT WOS:A1996UW48800030 PM 8695813 ER PT J AU Chesi, M Bergsagel, PL Brents, LA Smith, CM Gerhard, DS Kuehl, WM AF Chesi, M Bergsagel, PL Brents, LA Smith, CM Gerhard, DS Kuehl, WM TI Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines SO BLOOD LA English DT Article ID POLYMERASE CHAIN-REACTION; CENTROCYTIC LYMPHOMA; CHROMOSOMAL TRANSLOCATION; BCL-1 LOCUS; GENE; BREAKPOINTS; PROTEIN; PRAD1; OVEREXPRESSION; REARRANGEMENT AB Translocations involving the IgH locus at chromosomal locus 14q32.3 are a common eventin many B-cell malignancies. The translocations, which generally occur into JH and switch regions, are mediated by errors in the two developmentally regulated, lymphocyte-specific pathways: VDJ- and switch-mediated recombination, Dysregulation of cyclin D1 by a t(11;14)(q13;q32) translocation occurs in most cases of mantle-cell lymphoma and in approximately 30% of multiple myeloma (MM) tumors in which a 14q32 translocation can be detected. We show here that in two of three myeloma lines that overexpress cyclin D1, there is an 11;14 translocation into a gamma switch region, suggesting an error in switch recombination. By contrast, 11;14 translocations in mantle-cell lymphoma are invariably into or near a JH segment, suggesting an error in VDJ recombination, This is consistent with the fact that myeloma cells have undergone IgH switch recombination, whereas mantle-cell lymphoma cells generally have not. (C) 1996 by The American Society of Hematology. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. CORNELL UNIV MED COLL,DIV HEMATOL ONCOL,NEW YORK,NY. WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NHGRI NIH HHS [HG00002] NR 46 TC 176 Z9 178 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1996 VL 88 IS 2 BP 674 EP 681 PG 8 WC Hematology SC Hematology GA UW488 UT WOS:A1996UW48800032 PM 8695815 ER PT J AU Bergan, R Hakim, F Schwartz, GN Kyle, E Cepada, R Szabo, JM Fowler, D Gress, R Neckers, L AF Bergan, R Hakim, F Schwartz, GN Kyle, E Cepada, R Szabo, JM Fowler, D Gress, R Neckers, L TI Electroporation of synthetic oligodeoxynucleotides: A novel technique for ex vivo bone marrow purging SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; C-MYC; ANTISENSE OLIGODEOXYNUCLEOTIDE; OLIGONUCLEOTIDE; TRANSPLANTATION; EXPRESSION; INHIBITION; LYMPHOMA; LEUKEMIA; GROWTH AB Recent data suggest that tumor cells contaminating reinfused bone marrow may contribute to relapse in patients undergoing autologous bone marrow transplantation. Purging strategies that are able to remove these contaminating tumor cells need to be developed. This study describes how electroporation (EP) can be used to improve intracellular delivery of synthetic antisense oligodeoxynucleotides (ODNs), thereby enhancing their ability to suppress a target protein. Antisense ODNs that were introduced into cells by EP led to immediate suppression of targeted c-myc protein; this was associated with rapid cell death in the diffuse histiocytic lymphoma, U937; Burkitt's lymphoma, ST486; breast carcinoma, MCF-7; and Ewing's sarcoma, CHP-100, cell lines. Electroporation was found to have little or no detrimental effect on cells responsible for murine hematopoietic long-term reconstitution as determined from in vivo competitive repopulation studies. Using human c-myc-directed antisense ODNs as a model for the application of this approach to bone marrow purging, selective killing of human lymphoma U937 cells relative to normal human bone marrow cells was shown in cell mixing studies, In vivo studies were performed in which a survival advantage was shown for athymic mice that were inoculated with antisense-treated U937 cells as opposed to control cells. These studies suggest that EP of bone marrow may be of use in enhancing intracellular delivery of a variety of molecular/pharmaceutical agents. Taken together, these data suggest that the use of electroporation to enhance delivery of antisense ODNs is a promising new approach towards ex vivo bone marrow purging. (C) 1996 by The American Society of Hematology. C1 NCI,MED BRANCH,NATL INST HLTH,BETHESDA,MD 20892. RP Bergan, R (reprint author), NCI,CLIN PHARMACOL BRANCH,NATL INST HLTH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 51 TC 60 Z9 60 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1996 VL 88 IS 2 BP 731 EP 741 PG 11 WC Hematology SC Hematology GA UW488 UT WOS:A1996UW48800039 PM 8695822 ER PT J AU Silberstein, LE George, A Durdik, JM Kipps, TJ AF Silberstein, LE George, A Durdik, JM Kipps, TJ TI The V4-34 encoded anti-i autoantibodies recognize a large subset of human and mouse B-cells SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE cold agglutinins; murine and human; B lymphocytes; V(H)4-34 gene ID COLD-REACTING AUTOANTIBODIES; LEUKOCYTE COMMON ANTIGEN; GENE SEGMENT; SIGNAL TRANSDUCTION; HUMAN-LYMPHOCYTES; BIOLOGIC ACTIVITY; T-CELLS; AGGLUTININS; CD45; SPECIFICITY AB Autoantibodies to the i, I and Pr-2 carbohydrate determinants bind red blood cells, preferentially at low temperature in vitro, Using multiparameter flow cytometric analyses, we demonstrate that each of these autoantibodies also react with human and mouse lymphocytes at physiologic temperatures. The anti-Pr-2 autoantibody recognizes a glycoprotein determinant(s) expressed by a subset of both T and B lymphocytes. In contrast, the binding of anti-i and anti-I antibodies each is restricted to B-lymphocytes, The anti-i autoantibody binds to over 50% of all B cells, whereas the anti-I antibody reacts with less than 10% of either tonsillar or blood B cells, Prior studies identified that the B cell isoform of CD45 (B220) has the linear poly-N-acetyllactosamine that forms the ''i'' determinant, Because anti-B220 antibodies recently have been reported to influence T-dependent B-cell. isotype switching, we tested each antibody for its ability to influence the production of secondary Ig isotypes by murine splenocytes co-cultured with a stimulator helper T cell clone, We find that addition of anti-i antibody increases the proportion of B cells secreting secondary Ig isotypes, In contrast, the anti-I antibody had no such effect, These findings imply that stimulation of B cells through the highly conserved carbohydrate determinant that forms the ''i'' antigen may be of physiologic importance in T-dependent B-cell differentiation. C1 NIDR,NIH,SECT MUCOSAL IMMUNOL,BETHESDA,MD 20892. UNIV ARKANSAS,DEPT BIOL SCI,FAYETTEVILLE,AR 72701. UNIV CALIF SAN DIEGO,DEPT MED,SAM & ROSE STEIN INST RES AGING,LA JOLLA,CA 92093. RP Silberstein, LE (reprint author), UNIV PENN,MED CTR,284 JOHN MORGAN BLDG,PHILADELPHIA,PA 19104, USA. FU NIA NIH HHS [AG04100]; NIDDK NIH HHS [DK39065]; NIGMS NIH HHS [GM48691] NR 44 TC 34 Z9 34 U1 0 U2 0 PU BLOOD CELLS FOUNDATION PI LA LOLLA PA C/O ERNEST BEUTLER SCRIPPS RES INST, DEPT MOLECULAR EXP MEDICINE, LA LOLLA, CA 92037 SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL 15 PY 1996 VL 22 IS 13 BP 126 EP 138 DI 10.1006/bcmd.1996.0020 PG 13 WC Hematology SC Hematology GA UY512 UT WOS:A1996UY51200001 PM 8931953 ER PT J AU Bernard, M Pierre, VB Klein, DC AF Bernard, M Pierre, VB Klein, DC TI Hydroxyindole-O-methyltransferase in Y-79 cells: Regulation by serum SO BRAIN RESEARCH LA English DT Article DE hydroxyindole-O-methyltransferase; melatonin; Y-79 retinoblastoma; serum; S-antigen ID HUMAN RETINOBLASTOMA CELLS; N-ACETYLTRANSFERASE; PINEAL-GLAND; MELATONIN PRODUCTION; BINDING PROTEIN; DIFFERENTIATION; RAT; CULTURE AB Hydroxyindole-O-methyltransferase (HIOMT) catalyzes the last step in the synthesis of melatonin. In the present study, the regulation of HIOMT expression was examined in the human Y-79 retinoblastoma cell line. Cells were grown in suspension culture using medium supplemented with 10% fetal calf serum (FCS). HIOMT activity and mRNA were strongly reduced when FCS was substituted with 0.1% bovine serum albumin (BSA), and were restored by addition of FCS. The effect of FCS on HIOMT expression was relatively selective, because the abundance of mRNA encoding actin, G3PDH or interphotoreceptor retinoid-binding protein did not change following serum deprivation. However, S-antigen (arrestin) mRNA was regulated by serum coordinately with HIOMT mRNA, suggesting that S-antigen expression is also controlled by a serum factor. The effect of serum on HIOMT expression was net duplicated by treatment with a series of known differentiating factors, nor was it reduced by dialysis or stripping procedures which remove steroids, growth factors and thyroid hormones. C1 NICHHD,DEV NEUROBIOL LAB,SECT NEUROENDOCRINOL,BETHESDA,MD 20892. CNRS,URA 1869,BIOL CELLULAIRE LAB,F-86022 POITIERS,FRANCE. NR 30 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 15 PY 1996 VL 727 IS 1-2 BP 118 EP 124 PG 7 WC Neurosciences SC Neurosciences & Neurology GA UZ747 UT WOS:A1996UZ74700013 PM 8842389 ER PT J AU Sakr, WA Wheeler, TM Blute, M Bodo, M CalleRodrigue, R Henson, DE Mostofi, FK Seiffert, J Wojno, K Zincke, H AF Sakr, WA Wheeler, TM Blute, M Bodo, M CalleRodrigue, R Henson, DE Mostofi, FK Seiffert, J Wojno, K Zincke, H TI Workgroup 2 - Staging and reporting of prostate cancer - Sampling of the radical prostatectomy specimen SO CANCER LA English DT Article; Proceedings Paper CT International Consultation on Prostatic Intraepithelial Neoplasia and Pathologic Staging of Prostatic Carcinoma CY NOV 03-04, 1995 CL MAYO CLIN, ROCHESTER, MN HO MAYO CLIN C1 KARMANOS CANC INST,DETROIT,MI. METHODIST HOSP,DEPT PATHOL,HOUSTON,TX 77030. MAYO CLIN,DEPT UROL,ROCHESTER,MN. POSTGRAD MED UNIV,ST JOHNS HOSP,DEPT PATHOL,BUDAPEST,HUNGARY. NCI,EARLY DETECT BRANCH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT GENITOURINARY MED,WASHINGTON,DC 20306. NATL CANC REGISTRARS ASSOC,SACRAMENTO,CA. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. RP Sakr, WA (reprint author), WAYNE STATE UNIV,HARPER HOSP,DEPT PATHOL,3990 JOHN R,DETROIT,MI 48201, USA. NR 0 TC 78 Z9 78 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUL 15 PY 1996 VL 78 IS 2 BP 366 EP 368 DI 10.1002/(SICI)1097-0142(19960715)78:2<366::AID-CNCR29>3.3.CO;2-3 PG 3 WC Oncology SC Oncology GA UV022 UT WOS:A1996UV02200029 PM 8674019 ER PT J AU Su, YA Ray, ME Lin, T Seidel, NE Bodine, DM Meltzer, PS Trent, JM AF Su, YA Ray, ME Lin, T Seidel, NE Bodine, DM Meltzer, PS Trent, JM TI Reversion of monochromosome-mediated suppression of tumorigenicity in malignant melanoma by retroviral transduction SO CANCER RESEARCH LA English DT Article ID INSERTIONAL MUTAGENESIS; IDENTIFICATION; CHROMOSOME-6; RESISTANCE; SELECTION; FRAGMENTS; CANCER; SITE AB We have developed a general strategy to reverse monochromosome suppression of the malignant phenotypes by retroviral transduction. Our approach involved the introduction of a retroviral expression vector-carried cDNA library into a chromosome 6-suppressed melanoma subline UACC-903(+6) [J. M. Trent et al., Science (Washington DC), 247: 568-571, 1990]. The cDNA library was constructed from polyadenylated RNA isolated from the suppressed UACC-903(+6) cells, packaged into high-titer amphotropic retrovirus particles, and transduced into UACC-903(+6) cells. Revertant his(R) transductants were selected by isolating colony-forming cells in soft agar. A total of 121 large (>150 mu m) colonies was picked from soft agar culture with 18 of 121 (15%) established as permanent sublines. The revertant sublines demonstrated 7-58% cloning efficiency upon plating in agar, in contrast to <0.05% for the UACC-903(+6) subline. All 18 revertant sublines, termed SRS1-SRS18 (for ''selection of revertants for suppression''), displayed a reduced population-doubling time, with 9 of 18 showing focus formation in monolayer similar to the parental (nonsuppressed) cell line. Preliminary evidence for reversion of the suppressed phenotype by injection of cells into athymic nude mice has been completed for one revertant subline. Southern analysis has demonstrated integration of the retroviral vector sequence in all 18 sublines. This approach should facilitate the identification of genes involved in the tumorigenic phenotype of malignant melanoma, and is readily adaptable to other model systems. C1 NATL CTR HUMAN GENOME RES,NIH,CANC GENET LAB,BETHESDA,MD 20892. NATL CTR HUMAN GENOME RES,NIH,LAB GENE TRANSFER,BETHESDA,MD 20892. NR 30 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1996 VL 56 IS 14 BP 3186 EP 3191 PG 6 WC Oncology SC Oncology GA UW674 UT WOS:A1996UW67400006 PM 8764103 ER PT J AU Zhuang, SM Eklund, LK Cochran, C Rao, GN Wiseman, RW Soderkvist, P AF Zhuang, SM Eklund, LK Cochran, C Rao, GN Wiseman, RW Soderkvist, P TI Allelotype analysis of 2',3'-dideoxycytidine- and 1,3-butadiene-induced lymphomas in B6C3F1 mice SO CANCER RESEARCH LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; COLORECTAL CARCINOMAS; FREQUENT LOSS; RETINOBLASTOMA; CHROMOSOME; NEOPLASIA; PROTEIN; GENE; IDENTIFICATION; HETEROZYGOSITY AB To identify potential tumor suppressor genes involved in lymphoma development, we generated allelotypes of 16 2',3'-dideoxycytidine (ddC) and 31 1,3-butadiene (BD)-induced lymphomas from C57BL/6 x C3H/He F1 (hereafter called B6C3F1) mice. Two or more anonymous simple sequence length polymorphisms per autosome were examined for loss of heterozygosity (LOH), Allelic losses throughout the genome were generally infrequent, except for markers on chromosome 2, 4, 11 and 12, The highest frequency of allelic losses was observed on chromosome 12, with 38 and 39% in ddC and ED-induced lymphomas, respectively. The most prevalent LOH was localized to the distal region hounded by markers D12Mit263 and D12Nds2. No known tumor suppressor genes have been mapped to this region, and no obvious candidates could be identified, suggesting the presence of novel suppressor gene(s), LOH on chromosome 2 was observed in 31% of ddC-induced lymphomas but in only 3% (1/31) of ED-induced lymphomas, suggesting a ddC-specific genetic effect, Detailed analysis Localized a potential tumor suppressor gene residing on the distal region of chromosome 2, between markers D2Mit147 and D2Mit148. Twenty-five % of ddC-induced and 23% of BD-induced lymphomas showed LON on chromosome 4, and two discrete regions were identified, One of the regions includes the IFN gene cluster and is syntenic to human chromosome 9p21-22, Candidate tumor suppressor genes, Mts1 (multiple tumor suppressor 1) and Mts2 have been mapped to this region, The second region is located on the distal Dart of chromosome 4, which is homologous to human chromosome 1p35-36, a region that is frequently deleted in various types of human tumors. Finally, 19% of ddC-induced and 29% of BD-induced lymphomas revealed LOH on chromosome 11 at the Acrb locus, which lies within 1 cM of p53, suggesting that the p53 tumor suppressor gene also plays a role in lymphomagenesis. These results suggest that multiple potential suppressor loci contribute to lymphoma development in B6C3F1 mice. C1 LINKOPING UNIV HOSP,FAC HLTH SCI,DEPT OCCUPAT & ENVIRONM MED,S-58185 LINKOPING,SWEDEN. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NR 51 TC 35 Z9 35 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1996 VL 56 IS 14 BP 3338 EP 3343 PG 6 WC Oncology SC Oncology GA UW674 UT WOS:A1996UW67400034 PM 8764131 ER PT J AU JohnsonThompson, M Sullivan, C Olden, K AF JohnsonThompson, M Sullivan, C Olden, K TI NIEHS/AACR Task Force on the advancement of minorities in science: Vision for a model program SO CANCER RESEARCH LA English DT Article AB The National Institute of Environmental Health Sciences/National Institutes of Health and the American Association for Cancer Research initiated the ''NIEHS/AACR Task Force on the Advancement of Minorities in Science'' to address the issues of recruitment, participation, retention, and advancement of historically underrepresented minorities in the biomedical sciences. The goal of the Task Force was to establish a model program, national in scope and significance, to increase the number of historically underrepresented minorities who earn a doctorate and excel professionally in the biomedical sciences. To this end, the model program will: seek to promote systemic change in educational institutions from precollege through graduate school; introduce effective models of diversity training for faculty and students from precollege through university; promote collaborative learning, leadership skills, and team building in science; focus on the professional development of teachers; depend on the commitment and collaboration of financial and philosophical partners for its implementation. This document represents the vision for the model program, developed by an eight-member subcommittee charged with representing and documenting the concerns and opinions of the Task Force as a whole. RP JohnsonThompson, M (reprint author), NIEHS, NIH, OFF INST DIVERSITY, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 26 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1996 VL 56 IS 14 BP 3380 EP 3386 PG 7 WC Oncology SC Oncology GA UW674 UT WOS:A1996UW67400040 ER PT J AU Gawrisch, K Holte, LL AF Gawrisch, K Holte, LL TI NMR investigations of non-lamellar phase promoters in the lamellar phase state SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article DE nuclear magnetic resonance; phospholipid; hexagonal phase; polyunsaturation; alkane; alcohol ID NUCLEAR-MAGNETIC-RESONANCE; HEXAGONAL-HII PHASE; PROTEIN-KINASE-C; ORIENTATIONAL ORDER PROFILE; CHAIN-LENGTH DEPENDENCE; LIPID BILAYER-MEMBRANES; X-RAY-DIFFRACTION; ACYL-CHAIN; L-ALPHA; PHOSPHOLIPID-BILAYERS AB A delicate balance of attractive and repulsive forces between lipid molecules determines the average area per lipid in the liquid crystalline lamellar phase. Formation of inverted non-lamellar phases is linked to an imbalance in lateral tension between lipid headgroups and chains favoring formation of curved lipid monolayers, such as in Inverse hexagonal (H-II) and cubic phases. If assembled in bilayers, non-lamellar forming lipids are under a curvature related lateral stress. This tension imbalance influences molecular cross-sectional area in the lamellar phase which is reflected in order parameter changes of a perdeuterated lipid chain. H-2 NMR order parameters are sensitive to variations as small as 0.2 Angstrom(2) in area per molecule. Curvature stress caused by a reduction of repulsive forces between headgroups, e.g. replacement of PC with PE raises chain order and reduces area per lipid by a few square angstrom. Stress caused by increased repulsive tension between lipid hydrocarbon chains, e.g. an increase in chain length, chain unsaturation or a rise in temperature, lowers chain order and increases area per molecule. Addition of alkanes, alcohols, cholesterol and other substances also changes lipid order, but interpretation of these changes in terms of tension in headgroup and chain regions does not follow simple patterns. In addition to altering tension, these additives may stabilize non-lamellar phases by lowering interstitial energies. RP Gawrisch, K (reprint author), NIAAA,NIH,LAB MEMBRANE BIOCHEM & BIOPHYS,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 92 TC 49 Z9 49 U1 1 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD JUL 15 PY 1996 VL 81 IS 2 BP 105 EP 116 DI 10.1016/0009-3084(96)02576-5 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VG156 UT WOS:A1996VG15600002 ER PT J AU Chernomordik, L AF Chernomordik, L TI Non-bilayer lipids and biological fusion intermediates SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article DE non-bilayer lipids; membrane fusion; curvature ID MEDIATED MEMBRANE-FUSION; PH-DEPENDENT FUSION; INFLUENZA-VIRUS HEMAGGLUTININ; ERYTHROCYTE GHOST MEMBRANES; PHASE-TRANSITION; PHOSPHOLIPID-VESICLES; CELL-FUSION; FATTY-ACIDS; IMMUNODEFICIENCY-VIRUS; TARGET MEMBRANE AB Disparate biological fusion reactions and fusion of purely lipid bilayers are similarly influenced by 'non-bilayer' lipids (lipids which do not form lipid bilayers in water by themselves). Lipid composition of membranes affects biological fusion at a stage downstream of activation of fusion proteins and prior to fusion pore formation. These data suggest that actual merger of membrane lipid bilayers in different fusion reactions proceeds via the same pathway. The effects of non-bilayer lipids specifically correlate with their ability to bend lipid monolayers in different directions, and appear to be consistent with the specific hypothesis of membrane fusion suggesting that fusion proceeds through highly bent intermediates - stalks, local connections between contacting monolayers of fusing membranes. RP Chernomordik, L (reprint author), NICHHD,NIH,THEORET & PHYS BIOL LAB,BLDG 10,ROOM 10D04,10 CTR DR,BETHESDA,MD 20892, USA. NR 88 TC 158 Z9 159 U1 2 U2 15 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD JUL 15 PY 1996 VL 81 IS 2 BP 203 EP 213 DI 10.1016/0009-3084(96)02583-2 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VG156 UT WOS:A1996VG15600009 PM 8810049 ER PT J AU Ooi, CE Rabinovich, E Dancis, A Bonifacino, JS Klausner, RD AF Ooi, CE Rabinovich, E Dancis, A Bonifacino, JS Klausner, RD TI Copper-dependent degradation of the Saccharomyces cerevisiae plasma membrane copper transporter Ctr1p in the apparent absence of endocytosis SO EMBO JOURNAL LA English DT Article DE copper homeostasis; copper transporter; endocytosis; plasma membrane protein turnover; protein degradation ID FACTOR PHEROMONE RECEPTOR; GENE ENCODES; ALPHA-FACTOR; PLASMINOGEN-ACTIVATOR; INTERNALIZATION STEP; PEP4 GENE; YEAST; PROTEIN; IDENTIFICATION; LIGAND AB The cell surface protein repertoire needs to be regulated in response to changes in the extracellular environment. In this study, we investigate protein turnover of the Saccharomyces cerevisiae plasma membrane copper transporter Ctr1p, in response to a change in extracellular copper levels. As Ctr1p mediates high affinity uptake of copper into the cell, modulation of its expression is expected to be involved in copper homeostasis. We demonstrate that Ctr1p is a stable protein when cells are grown in low concentrations of copper, but that exposure of cells to high concentrations of copper (10 mu M) triggers degradation of cell surface Ctr1p. This degradation appears to be specific for Ctr1p and does not occur with another yeast plasma membrane protein tested. Internalization of some Ctr1p can be seen when cells are exposed to copper. However, yeast mutant strains defective in endocytosis (end3, end4 and chc1-ts) and vacuolar degradation (pep4) exhibit copper-dependent Ctr1p degradation, indicating that internalization and delivery to the vacuole is not the principal mechanism responsible for degradation. In addition, a variant Ctr1p with a deletion in the cytosolic tail is not internalized upon exposure of cells to copper, but is nevertheless degraded. These observations indicate that proteolysis at the plasma membrane most likely explains copper-dependent turnover of Ctr1p and point to the existence of a novel pathway in yeast for plasma membrane protein turnover. C1 TEL AVIV UNIV, DEPT BIOCHEM, IL-69978 TEL AVIV, ISRAEL. RP NICHHD, NATL INST HLTH, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 54 TC 151 Z9 156 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD JUL 15 PY 1996 VL 15 IS 14 BP 3515 EP 3523 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UY922 UT WOS:A1996UY92200004 PM 8670854 ER PT J AU Murata, T Taira, M Manganiello, VC AF Murata, T Taira, M Manganiello, VC TI Differential expression of cGMP-inhibited cyclic nucleotide phosphodiesterases in human hepatoma cell lines SO FEBS LETTERS LA English DT Article DE Human hepatoma cell line; PDE3 or cGMP-inhibited cyclic nucleotide phosphodiesterase; PDE4 or cAMP-specific phosphodiesterase ID HUMAN HEPATOCELLULAR-CARCINOMA; AORTIC SMOOTH-MUSCLE; AMP PHOSPHODIESTERASE; CAMP PHOSPHODIESTERASE; SELECTIVE INHIBITORS; MOLECULAR-CLONING; RAT-LIVER; INSULIN; PURIFICATION; IV AB PDE3 or cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI PDE) activity was detected in homogenates of HepG2, Hep3B and HuH7, but not SK-Hep-1, human hepatoma cells, In HepG2 and Hep3B cells PDE3 activity was found predominantly in particulate fractions; in HuH7, in both particulate and supernatant fractions. cDNAs encoding two human PDE3s (an 'adipocyte' type, HcGIP1, and a 'cardiovascular' type, HcGIP2) have been cloned, HcGIP1 cDNA hybridized strongly with poly(A)(+) RNA species from HepG2 and Hep3B, Both HcGIP1 and HcGIP2 mRNAs were expressed in Hep3B and HuH7 cells, The nucleotide sequence of an similar to 300-bp cDNA fragment, isolated after RT-PCR cloning from HepG2 RNA, was identical to a sequence within the conserved domain of HcGIP1 cDNA, consistent with the presence of HcGIP1 mRNA in HepG2 cells. C1 NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. NR 37 TC 13 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 15 PY 1996 VL 390 IS 1 BP 29 EP 33 DI 10.1016/0014-5793(96)00410-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UY074 UT WOS:A1996UY07400007 PM 8706823 ER PT J AU Russell, MW Munroe, DJ Bric, E Housman, DE DietzBand, J Riethman, HC Collins, FS Brody, LC AF Russell, MW Munroe, DJ Bric, E Housman, DE DietzBand, J Riethman, HC Collins, FS Brody, LC TI A 500-kb physical map and contig from the Harvey ras-1 gene to the 11p telomere SO GENOMICS LA English DT Article ID SEQUENCE ORGANIZATION; HUMAN CHROMOSOME-11; SHORT ARM; REGIONS; DNA; POLYMORPHISM; MARKERS; HRAS AB A contiguous physical map was constructed from the Harvey ras-l (HRAS1) gene to the lip telomere. The contig spans approximately 500 kb and is minimally composed of a telomere-containing YAC and P1 and cosmid clones. Included in the contig are 11 sequence-tagged sites derived from P1 and cosmid ends. Three genes were placed on the contig in the following order: telomere-ribonuclease/angiogenin inhibitor (RNH)-Harvey ras-1 (HRAS1)-HRAS1-related complex (HRC). Two novel tetranucleotide repeats (heterozygosity of 66 and 68%) and a complex CA repeat (heterozygosity of 78%) were isolated and characterized. (C) 1996 Academic Press, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT PEDIAT & COMMUNICABLE DIS,ANN ARBOR,MI 48109. UNIV MICHIGAN,DIV HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. ONCOR INC,DEPT RES & DEV,GAITHERSBURG,MD 20877. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. NR 33 TC 9 Z9 9 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1996 VL 35 IS 2 BP 353 EP 360 DI 10.1006/geno.1996.0367 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UX825 UT WOS:A1996UX82500010 PM 8661149 ER PT J AU Yoshikawa, T DuPont, BR Leach, RJ DeteraWadleigh, SD AF Yoshikawa, T DuPont, BR Leach, RJ DeteraWadleigh, SD TI New variants of the human and rat nuclear hormone receptor, TR4: Expression and chromosomal localization of the human gene SO GENOMICS LA English DT Article ID CELL LUNG-CANCER; STEROID-RECEPTOR; SUPERFAMILY; DELETION; CLONING; REGION; LOCUS AB TRA is a new member of the nuclear hormone receptor family. This receptor is highly conserved in rat and human, but an in-frame insertion of 19 amino acid residues in the amino-terminal (A/B) region was found in the human homolog, which we refer to as hTR4 alpha 1. By reverse transcription-PCR (RT-PCR) we have identified a human TR4 mRNA (hTR4 alpha 2) that is analogous in size and sequence to the reported rat TRA. RT-PCR analysis using total RNA derived from various rat tissues revealed a new rat TR4 transcript, referred to as rTR4 alpha 1, which is homologous to hTR4 alpha 1 since it contains the extra 19 amino acids in the A/B region, The two rat transcripts showed a differential tissue distribution. Analysis of the exon-intron organization of the hTR4 A/B region showed that the 19-amino acid peptide insert in hTR4 alpha 1 was encoded by a separate exon, indicating that hTR4 alpha 1 and hTR4 alpha 2 transcripts were produced by the differential usage of the exon. RT-PCR analysis revealed that both hTR alpha 1 and hTR4 alpha 2 were detectable in brain, placenta, and ovary. In contrast, the human ovarian cancer cell Line, PA1, failed to express hTR4 alpha 1. By fluorescence in situ hybridization, we have mapped the hTR4 gene to 3p25, a region deleted in some forms of cancer. (C) 1996 Academic Press, Inc. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RP Yoshikawa, T (reprint author), NIMH,CLIN NEUROGENET BRANCH,UNIT GENE MAPPING & EXPRESS,BLDG 10,ROOM 3N218,BETHESDA,MD 20892, USA. FU NHGRI NIH HHS [P01 HG00470] NR 24 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1996 VL 35 IS 2 BP 361 EP 366 DI 10.1006/geno.1996.0368 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UX825 UT WOS:A1996UX82500011 PM 8661150 ER PT J AU Ohshima, T Kozak, CA Nagle, JW Pant, HC Brady, RO Kulkarni, AB AF Ohshima, T Kozak, CA Nagle, JW Pant, HC Brady, RO Kulkarni, AB TI Molecular cloning and chromosomal mapping of the mouse gene encoding cyclin-dependent kinase 5 regulatory subunit p35 SO GENOMICS LA English DT Article ID DIRECTED PROTEIN-KINASE; CDC2-LIKE KINASE; EXPRESSION AB A neural-specific activating subunit, p35, of cyclin-dependent kinase 5 (Cdk5) was recently reported to differ from other mammalian cyclins, suggesting a new type of regulatory subunit for Cdk activity. The mouse gene encoding p35, Cdk5r, was isolated from a mouse 129/SvJ genomic library, and the genomic structure of Cdk5r was characterized. The most notable features of Cdk5r are the absence of introns in the amino acid coding region and the high homology of amino acid sequence among species. The 5'-flanking region of Cdk5r contained no canonical TATA or CAAT box but had several putative promoter elements, including Spl, AP2, MRE, and NGFIA. The mouse Cdk5r transcript was detected only in the brain by Northern blot analysis, Mouse Cdk5r was mapped to a position on mouse chromosome 11. (C) 1996 Academic Press, Inc. C1 NIDR,GENE TARGETING RES & CORE FACIL,NIH,BETHESDA,MD 20892. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,NEUROGENET SECT,BETHESDA,MD 20892. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 14 TC 34 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1996 VL 35 IS 2 BP 372 EP 375 DI 10.1006/geno.1996.0370 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UX825 UT WOS:A1996UX82500013 PM 8661152 ER PT J AU Cerretti, DP Copeland, NG Gilbert, DJ Jenkins, NA Kuefer, MU Valentine, V Shapiro, DN Cui, XL Morris, SW AF Cerretti, DP Copeland, NG Gilbert, DJ Jenkins, NA Kuefer, MU Valentine, V Shapiro, DN Cui, XL Morris, SW TI The gene encoding LERK-7 (EPLG7, Epl7), a ligand for the Eph-related receptor tyrosine kinases, maps to human chromosome 5 at band q21 and to mouse chromosome 17 SO GENOMICS LA English DT Article ID PROTEIN AB The eph-related receptors are the largest subfamily of receptor tyrosine kinases. Recently, we and others have identified seven different, but related, cDNAs encoding membrane-bound ligands for this family of receptors. One member, LERK-7, is attached to the cell membrane via glycosyl-phosphatidylinositol linkage and has been found to be a ligand for the eph-family receptors hek, elk, eck, and rek. Using PCR-based screening of human x rodent somatic cell hybrid DNAs, we have assigned the gene that encodes LERK-7 (EPLG7) to human chromosome 5, Fluorescence in situ hybridization to metaphase chromosome preparations using a genomic clone from the locus refined this localization to chromosome 5, band q21. In addition, Southern blot analysis of DNAs from interspecific backcross mice indicated that the mouse homologue Ep17 maps to a homologous region on chromosome 17. (C) 1996 Academic Press, Inc. C1 IMMUNEX RES & DEV CORP, DEPT MOLEC BIOL, SEATTLE, WA 98101 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. ST JUDE CHILDRENS RES HOSP, DEPT EXPTL ONCOL, MEMPHIS, TN 38101 USA. ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38101 USA. FU NCI NIH HHS [CA 69129, CA 21765, CA 01702] NR 20 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1996 VL 35 IS 2 BP 376 EP 379 DI 10.1006/geno.1996.0371 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UX825 UT WOS:A1996UX82500014 PM 8661153 ER PT J AU McDiarmid, R Xing, X AF McDiarmid, R Xing, X TI On the energetics of the lower excited states of N-methylpyrrole SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID ABSORPTION-SPECTRUM; CYCLOPENTADIENE; PYRROLE; FURAN; TRANSITION; IONIZATION AB An absorption, fluorescence excitation, and (2+1) resonantly enhanced multiphoton ionization spectroscopic investigation was carried out on the lowest excited state of N-methylpyrrole (NMP). Transitions to and from this state were shown to give rise to the structured bands observed around 240 nm. An energy-dissipative channel was found that was only slightly higher in energy. Possible assignments of this channel in NMP and its relation to the states of pyrrole are discussed. C1 NIH,BETHESDA,MD 20892. NR 29 TC 20 Z9 20 U1 0 U2 6 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUL 15 PY 1996 VL 105 IS 3 BP 867 EP 873 DI 10.1063/1.471970 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA UW836 UT WOS:A1996UW83600001 ER PT J AU Gretz, JE Kaldjian, EP Anderson, AO Shaw, S AF Gretz, JE Kaldjian, EP Anderson, AO Shaw, S TI Commentary - Sophisticated strategies for information encounter in the lymph node - The reticular network as a conduit of soluble information and a highway for cell traffic SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HIGH ENDOTHELIAL VENULES; RAT; TISSUES; LOCALIZATION; LYMPHOCYTES; EMIGRATION; CYTOKINES; ANTIGEN; PROTEIN; VESSELS AB The lymph node is the crossroad in which soluble signals and cells carried by lymph meet lymphocytes emigrating from blood. Efficient interactions among these elements depend on the reticular network, which comprises reticular fibers, related extracellular matrix components, and associated fibroblastic reticular cells. This network provides a three-dimensional scaffold for attachment of APCs and pathways for the migration of T cells to these APCs. in addition, the network constitutes a miniature conduit system for bulk flow delivery of soluble molecules to distinct sites in the paracortex, particularly the high endothelial venule. The delivered mediators, such as chemokines, regulate the phenotype of the high endothelial venule, the recruitment of lymphocytes, and the behavior of the recruited lymphocytes. Thus, the reticular network is a multifunctional infrastructure that facilitates encounters of cells with other cells and factors necessary for effective and efficient immune surveillance. C1 NCI,HUMAN IMMUNOL SECT,EXPT IMMUNOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,DEPT RESP & MUCOSAL IMMUNOL,FT DETRICK,MD 21702. NR 55 TC 137 Z9 138 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1996 VL 157 IS 2 BP 495 EP 499 PG 5 WC Immunology SC Immunology GA UW154 UT WOS:A1996UW15400001 PM 8752893 ER PT J AU Vergelli, M Le, H vanNoort, JM DhibJalbut, S McFarland, H Martin, R AF Vergelli, M Le, H vanNoort, JM DhibJalbut, S McFarland, H Martin, R TI A novel population of CD4(+)CD56(+) myelin-reactive T cells lyses target cells expressing CD56/neural cell adhesion molecule SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; LEU-19 NKH-1 ANTIGEN; BASIC-PROTEIN; FINE SPECIFICITY; NK CELLS; LYMPHOCYTES; INVOLVEMENT; ANTIBODIES; LINES AB CD56 is a member of the neural cell adhesion molecule family expressed on cells of the central nervous system and also on NK cells. Previous studies suggest the involvement of CD56 in effector-to-target cell conjugation mediated by NK cells. It was shown recently that CD56 is also expressed by subpopulations of CD8(+) and CD4(+) T cells. The present study describes the functional characteristics of CD4(+)CD56(+) T cell lines established from blood of multiple sclerosis patients by stimulation with myelin basic protein (MBP). CD4(+)CD56(+), MBP-specific T cell lines were able to lyse MBP-pulsed target cells in an HLA class II-restricted fashion. At the same time, they mediated MHC-unrestricted lysis of CD56(+) target cells such as CD56(+) lymphoid or glial tumor cells, but not of the typical NK target, K562. A number of experimental results including separation of CD4(+)CD56(+) T cells into CD56 high and low expressing populations, cold target inhibition, as well as killing of CD56-transfected cells indicate that homotypic CD56 interactions are involved in the MHC-unrestricted lysis. CD56 interactions are not sufficient but are required for effector/target interaction. Our findings raise the possibility that CD4(+)CD56(+) T cells sharing properties of bath typical Ag-specific Th0-like T cells and NK cells might be involved in damage of tissues expressing CD56/neural cell adhesion molecule, such as the central nervous system. Thus, we provide evidence for a novel mechanism that could lead to organ-specific autoreactivity. C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. UNIV TUBINGEN,SCH MED,DEPT NEUROL,TUBINGEN,GERMANY. TNO,LEIDEN,NETHERLANDS. UNIV MARYLAND,SCH MED,DEPT NEUROL,BALTIMORE,MD 21201. OI van Noort, Johannes/0000-0002-9060-5921 NR 28 TC 53 Z9 53 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1996 VL 157 IS 2 BP 679 EP 688 PG 10 WC Immunology SC Immunology GA UW154 UT WOS:A1996UW15400025 PM 8752917 ER PT J AU Gazzinelli, RT Wysocka, M Hieny, S SchartonKersten, T Cheever, A Kuhn, R Muller, W Trinchieri, G Sher, A AF Gazzinelli, RT Wysocka, M Hieny, S SchartonKersten, T Cheever, A Kuhn, R Muller, W Trinchieri, G Sher, A TI In the absence of endogenous IL-1O, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4(+) T cells and accompanied by overproduction of IL-12, IFN-gamma, and TNF-alpha SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-10 PROTECTS MICE; INHIBITS CYTOKINE PRODUCTION; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; ACTIVATED MACROPHAGES; TRYPANOSOMA-CRUZI; ACCESSORY CELLS; LYMPHOCYTES-T; TH1 AB To examine the function of IL-10 synthesis during early infection with the intracellular protozoan Toxoplasma gondii, IL-10 knockout (KO) mice were inoculated with an avirulent parasite strain (ME-49). In contrast to control littermates that displayed 100% survival, the IL-10-deficient animals succumbed within the first 2 wk of the infection, with no evidence of enhanced parasite proliferation. The mortality in the IL-10 KO mice was associated with enhanced liver pathology characterized by increased cellular infiltration and intense necrosis. Levels of IL-12 and IFN-gamma in sera of infected IL-10-deficient animals were four- to sixfold higher than those in sera from control mice, as were mRNA levels for IFN-gamma, IL-1 beta, TNF-alpha, and IL-12 in lung tissue. Similarly, macrophages from IL-10 KO mice activated in vitro or in vivo with T. gondii produced higher levels of TNF-alpha and IL-12 than macrophages from control animals. Moreover, spleen cells from IL-10 KO mice infected with T. gondii secreted more IFN-gamma than splenocytes from nondeficient animals. In vitro depletion experiments indicated that CD4(+) lymphocytes are the major source of the latter cytokine in the spleen cell populations, and in vivo depletion with anti-CD4 Abs protected the IL-10 KO mice from parasite-induced mortality. Together the data suggest that endogenous IL-10 synthesis plays an important role in vivo in down-regulating monokine and IFN-gamma responses to acute intracellular infection, thereby preventing host immunopathology. C1 NIAID,IMMUNOBIOL SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,LAB HUMAN IMMUNOL,PHILADELPHIA,PA 19104. UNIV COLOGNE,INST GENET,W-5000 COLOGNE,GERMANY. UNIV FED MINAS GERAIS,DEPT BIOCHEM & IMMUNOL,BELO HORIZONT,MG,BRAZIL. RI Muller, Werner/B-9044-2008 OI Muller, Werner/0000-0002-1297-9725 NR 54 TC 596 Z9 609 U1 2 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1996 VL 157 IS 2 BP 798 EP 805 PG 8 WC Immunology SC Immunology GA UW154 UT WOS:A1996UW15400039 PM 8752931 ER PT J AU Jankovic, D Aslund, L Oswald, IP Caspar, P Champion, C Pearce, E Coligan, JE Strand, M Sher, A James, SL AF Jankovic, D Aslund, L Oswald, IP Caspar, P Champion, C Pearce, E Coligan, JE Strand, M Sher, A James, SL TI Calpain is the target antigen of a Th1 clone that transfers protective immunity against Schistosoma mansoni SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED NEUTRAL PROTEASE; NON-LIVING VACCINE; IRRADIATED CERCARIAE; ATTENUATED CERCARIAE; SEQUENCE-ANALYSIS; ESCHERICHIA-COLI; MICE; INDUCTION; ANTIBODY; PURIFICATION AB A CD4(+) clone (clone B), characterized as Th1 based on its selective production of IFN-gamma and IL-2, was established from C57Bl/6 mice protectively immunized against Schistosoma mansoni by intradermal vaccination with soluble worm Ags plus bacillus Calmette Guerin. In agreement with previous results demonstrating an IFN-gamma-dependent cell-mediated protective mechanism in this vaccination model, Ag-elicited peritoneal macrophages from syngeneic recipients of this clone were activated to kill schistosome larvae (schistosomula) in vitro. Moreover, recipients of clone B displayed significant resistance against cercarial challenge. By screening a battery of lambda gt11 clones from an adult worm cDNA library, one recombinant (25B) was identified that stimulated clone B specifically. Analysis of the 25B cDNA insert revealed a nucleotide sequence identical with that of the large subunit of schistosome calpain, a Ca2+-activated neutral proteinase. By expressing the products of PCR subcloning, we identified a 146-amino acid region of the 25B gene containing immunologic activity equivalent to the whole polypeptide. Overlapping peptides spanning this region were synthesized, and a core epitope was identified with the sequence EWKGAWCDGS. Since clone B responds to supernatants from cultured schistosomula, we postulate that the recognition of calpain released by invading larvae and resulting induction of Th1 cytokines accounts for the protection mediated by the adoptively transferred clone. Our findings thus implicate calpain as a target of protective immunity in schistosomes and provide the first example of a candidate vaccine Ag for this parasite identified on the basis of T cell reactivity. C1 NIAID, MOLEC STRUCT LAB, BETHESDA, MD 20892 USA. CORNELL UNIV, NEW YORK STATE COLL VET MED, DEPT MICROBIOL IMMUNOL & PARASITOL, ITHACA, NY 14853 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PHARMACOL & MOLEC SCI, BALTIMORE, MD 21205 USA. RP Jankovic, D (reprint author), NIAID, IMMUNOBIOL SECT,PARASIT DIS LAB,NIH, 9000 ROCKVILLE PIKE, BLDG 4-126, BETHESDA, MD 20892 USA. RI OSWALD, Isabelle/A-8497-2013; OI OSWALD, Isabelle/0000-0001-9918-277X NR 45 TC 47 Z9 52 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1996 VL 157 IS 2 BP 806 EP 814 PG 9 WC Immunology SC Immunology GA UW154 UT WOS:A1996UW15400040 PM 8752932 ER PT J AU Bencsics, C Wachtel, SR Milstien, S Hatakeyama, K Becker, JB Kang, UJ AF Bencsics, C Wachtel, SR Milstien, S Hatakeyama, K Becker, JB Kang, UJ TI Double transduction with GTP cyclohydrolase I and tyrosine hydroxylase is necessary for spontaneous synthesis of L-DOPA by primary fibroblasts SO JOURNAL OF NEUROSCIENCE LA English DT Article DE tetrahydrobiopterin; Parkinson's disease; gene therapy; retrovirus vector; transplantation; catecholamine ID PRODUCE L-DOPA; 6-HYDROXYDOPAMINE-TREATED RATS; BEHAVIORAL RECOVERY; BIOPTERIN COFACTOR; GENE-TRANSFER; CELLS; TETRAHYDROBIOPTERIN; BRAIN; CDNA; L-3,4-DIHYDROXYPHENYLALANINE AB Gene transfer of tyrosine hydroxylase (TH) in animal models of Parkinson's disease (PD), using either genetically modified cells or recombinant virus vectors, has produced partial restoration of behavioral and biochemical deficits. The limited success of this approach may be related to the availability of the cofactor, tetrahydrobiopterin (BH4), because neither the dopamine-depleted striatum nor the cells used for gene transfer possess a sufficient amount of BH4 to support TH activity. To determine the role of BH4 in gene therapy, fibroblast cells transduced with the gene for TH were additionally modified with the gene for GTP cyclohydrolase I, an enzyme critical for BH4 synthesis. In contrast to cells transduced with only TH, doubly transduced fibroblasts spontaneously produced both BH4 and 3,4-dihydroxy-L-phenylalanine. To examine further the importance of GTP cyclohydrolase I in gene therapy for PD, in vivo micro-dialysis was used to assess the biochemical changes in the dopamine-denervated striatum containing grafts of genetically modified fibroblasts. Only denervated striata grafted with fibroblasts possessing both TH and GTP cyclohydrolase I genes displayed biochemical restoration. However, no significant differences from controls were observed in apomorphine-induced rotation. This is partly attributable to a limited duration of gene expression in vivo. These differences between fibroblasts transduced with TH alone and those additionally modified with the GTP cyclohydrolase I gene indicate that BH4 is critical for biochemical restoration in a rat model of PD and that GTP cyclohydrolase I is sufficient for production of BH4. C1 UNIV CHICAGO,DEPT NEUROL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL SCI,CHICAGO,IL 60637. UNIV CHICAGO,COMM NEUROBIOL,CHICAGO,IL 60637. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT SURG,PITTSBURGH,PA 15261. UNIV MICHIGAN,DEPT BIOPSYCHOL,ANN ARBOR,MI 48104. FU NIDA NIH HHS [T32 DA07255]; NINDS NIH HHS [R29 NS32080, T32 NS07113] NR 48 TC 88 Z9 94 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 1996 VL 16 IS 14 BP 4449 EP 4456 PG 8 WC Neurosciences SC Neurosciences & Neurology GA UW879 UT WOS:A1996UW87900016 PM 8699255 ER PT J AU Portier, CJ KoppSchneider, A Sherman, CD AF Portier, CJ KoppSchneider, A Sherman, CD TI Calculating tumor incidence rates in stochastic models of carcinogenesis SO MATHEMATICAL BIOSCIENCES LA English DT Article ID ENZYME-ALTERED FOCI; QUANTITATIVE-ANALYSIS; CANCER; LIVER AB Multistage models of carcinogenesis are increasingly used in the estimation of risks from exposure to environmental agents. The two-stage model of carcinogenesis is routinely used because it agrees with much of the existing tumor incidence data, parallels the biological two-stage model, and has much of its mathematical details derived. However, recent findings on the mechanisms of carcinogenesis has led researchers to believe that there are a greater number of stages and a more complex structure to these models than a single pathway. In this paper, a method for readily computing tumor incidence rates for arbitrarily complex multistage models is derived. The formulas for the two-stage model with time-varying rates are given explicitly. Simple rules for more complicated models are given, and computer code able to implement these formulas are provided. C1 DEUTSCH KREBSFORSCHUNGSZENTRUM,D-6900 HEIDELBERG,GERMANY. RP Portier, CJ (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 38 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD JUL 15 PY 1996 VL 135 IS 2 BP 129 EP 146 DI 10.1016/0025-5564(96)00011-9 PG 18 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA UW168 UT WOS:A1996UW16800002 PM 8768218 ER PT J AU Davis, AF Ropp, PA Clayton, DA Copeland, WC AF Davis, AF Ropp, PA Clayton, DA Copeland, WC TI Mitochondrial DNA polymerase gamma is expressed and translated in the absence of mitochondrial DNA maintenance and replication SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ETHIDIUM-BROMIDE; TRANSCRIPTION; CELLS; BINDING; CLONING; YEAST AB Mitochondria are essential organelles in all eukaryotic cells where cellular ATP is generated through the process of oxidative phosphorylation. Protein components of the respiratory assembly are gene products of both mitochondrial and nuclear genes, The mitochondrial genome itself encodes several protein and nucleic acid components required for such oxidative phosphorylative processes, but the vast majority of genes encoding respiratory chain components are nuclear, Similarly, the processes of replication and transcription of mitochondrial DNA rely exclusively upon RNA and protein species encoded by nuclear genes, We have analyzed two key nuclear-encoded proteins involved in mitochondrial DNA replication and transcription as a function of the presence or absence of mitochondrial DNA, Mitochondrial DNA polymerase (DNA polymerase gamma), the nuclear-encoded enzyme which synthesizes mtDNA, is expressed and translated in cells devoid of mitochondrial DNA itself, In contrast, mitochondrial transcription factor A protein levels are tightly linked to the mtDNA status of the cell, These results demonstrate that the DNA polymerase gamma protein is stable in the absence of mitochondrial DNA, and that there appears to be no regulatory mechanism present in these cells to alter levels of this protein in the complete absence of mitochondrial DNA, Alternatively it is possible that this enzyme plays an additional, as yet undefined, role in the cell, thereby mandating its continued production. C1 NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709. RP Davis, AF (reprint author), STANFORD UNIV,SCH MED,BECKMAN CTR MOL & GENET MED,DEPT DEV BIOL,STANFORD,CA 94305, USA. FU NIGMS NIH HHS [GM33088-25] NR 36 TC 74 Z9 75 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 15 PY 1996 VL 24 IS 14 BP 2753 EP 2759 DI 10.1093/nar/24.14.2753 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UZ493 UT WOS:A1996UZ49300021 PM 8759007 ER PT J AU Umbach, DM Wilcox, AJ AF Umbach, DM Wilcox, AJ TI A technique for measuring epidemiologically useful features of birthweight distributions SO STATISTICS IN MEDICINE LA English DT Article ID BIRTH-WEIGHT; PERINATAL-MORTALITY; MAXIMUM-LIKELIHOOD; MODEL; RATIO AB Birthweight distributions have been conceptualized as a predominant Gaussian distribution contaminated in the tails by an unspecified 'residual' distribution. Acknowledging this idea, we propose a technique for measuring certain features of birthweight distributions useful to epidemiologists: the mean and variance of the predominant distribution; the proportions of births in the low- and high-birthweight residual distributions, and the boundaries of support for these residual distributions. Our technique, based on an underlying multinomial sampling distribution, involves estimating parameters in a mixture model for the multinomial bin probabilities after having chosen the support of the residual distribution with a model selection criterion. A modest simulation study and experience with a few actual datasets indicate that use of a Bayesian information criterion (BIG) as model selection criterion is superior to use of Akaike's information criterion (AIC) in this application. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP Umbach, DM (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 15 TC 21 Z9 21 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1996 VL 15 IS 13 BP 1333 EP 1348 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UX574 UT WOS:A1996UX57400002 PM 8841645 ER PT J AU James, KE Bloch, DA Lee, KK Kraemer, HC Fuller, RK AF James, KE Bloch, DA Lee, KK Kraemer, HC Fuller, RK TI An index for assessing blindness in a multi-centre clinical trial: Disulfiram for alcohol cessation - A VA Cooperative Study SO STATISTICS IN MEDICINE LA English DT Article ID DESIGN AB This paper considers an index to assess the success of blinding with application to a clinical trial of disulfiram. The index increases as the success of blinding increases, accounts for uncertain responses, and is scaled to an interval of 0.0 to 1.0, 0.0 being complete lack of blinding and 1.0 being complete blinding. C1 STANFORD UNIV,SCH MED,DEPT HLTH RES & POLCIY,STANFORD,CA 94305. VET ADM MED CTR,COOPERAT STUDIES PROGRAM COORDINATING CTR 151K,PALO ALTO,CA 94304. STANFORD UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,STANFORD,CA 94305. NIAAA,DEPT HLTH & HUMAN SERV,ROCKVILLE,MD 20892. RP James, KE (reprint author), OREGON HLTH SCI UNIV,VET AFFAIRS MED CTR,HLTH SERV RES & DEV 152,3710 SW US VET HOSP RD,PORTLAND,OR 97201, USA. NR 16 TC 64 Z9 66 U1 3 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1996 VL 15 IS 13 BP 1421 EP 1434 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UX574 UT WOS:A1996UX57400009 PM 8841652 ER PT J AU Hsiou, Y Ding, J Das, K Clark, AD Hughes, SH Arnold, E AF Hsiou, Y Ding, J Das, K Clark, AD Hughes, SH Arnold, E TI Structure of unliganded HIV-1 reverse transcriptase at 2.7 angstrom resolution: Implications of conformational changes for polymerization and inhibition mechanisms SO STRUCTURE LA English DT Article DE AIDS; drug design; mechanism of polymerization; non-nucleoside inhibition mechanism; polymerase structure ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONNUCLEOSIDE INHIBITORS; MUTATIONAL ANALYSIS; CRYSTAL-STRUCTURE; BINDING; COMPLEX; FINGERS; MODELS AB Background: HIV-1 reverse transcriptase (RT) is a major target for anti-HIV drugs. A considerable amount of information about the structure of RT is available, both unliganded and in complex with template-primer or nonnucleoside RT inhibitors (NNRTIs), But significant conformational differences in the p66 polymerase domain among the unliganded structures have complicated the interpretation of these data, leading to different proposals for the mechanisms of polymerization and inhibition, Results: We report the structure of an unliganded RT at 2.7 Angstrom resolution, crystallized in space group C2 with a crystal packing similar to that of the RT-NNRTI complexes. The p66 thumb subdomain is folded into the DNA-binding cleft, Comparison of the unliganded RT structures with the DNA-bound RT and the NNRTI-bound RT structures reveals that the p66 thumb subdomain can exhibit two different upright conformations. In the DNA-bound RT, the p66 thumb subdomain adopts an upright position that can be described as resulting from a rigid-body rotation of the p66 thumb along the 'thumb's knuckle' located near residues Trp239 (in strand beta 14) and Val317 (in beta 15) compared with the thumb position in the unliganded RT structure. NNRTI binding induces an additional hinge movement of the p66 thumb near the thumb's knuckle, causing the p66 thumb to adopt a configuration that is even more extended than in the DNA-bound RT structure, Conclusions: The p66 thumb subdomain is extremely flexible, NNRTI binding induces both short-range and long-range structural distortions in several domains of RT, which are expected to alter the position and conformation of the template-primer. These changes may account for the inhibition of polymerization and the alteration of the cleavage specificity of RNase H by NNRTI binding. C1 RUTGERS STATE UNIV, CTR ADV BIOTECHNOL & MED, PISCATAWAY, NJ 08854 USA. RUTGERS STATE UNIV, DEPT CHEM, PISCATAWAY, NJ 08854 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NIAID NIH HHS [AI 27690, AI 36144] NR 32 TC 237 Z9 242 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JUL 15 PY 1996 VL 4 IS 7 BP 853 EP 860 DI 10.1016/S0969-2126(96)00091-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UZ434 UT WOS:A1996UZ43400011 PM 8805568 ER PT J AU Liao, DI Silverton, E Seok, YJ Lee, BR Peterkofsky, A Davies, DR AF Liao, DI Silverton, E Seok, YJ Lee, BR Peterkofsky, A Davies, DR TI The first step in sugar transport: Crystal structure of the amino terminal domain of enzyme I of the E-coli PEP: Sugar phosphotransferase system and a model of the phosphotransfer complex with HPr SO STRUCTURE LA English DT Article DE enzyme I; HPr; phosphotransferase; sugar transport; X-ray crystallography ID BACTERIAL PHOSPHOENOLPYRUVATE; PROTEIN HPR; IDENTIFICATION; RESOLUTION AB Background: The bacterial phosphoenolpyruvate (PEP): sugar phosphotransferase system (PTS) transports exogenous hexose sugars through the membrane and tightly couples transport with phosphoryl transfer from PEP to the sugar via several phosphoprotein intermediates. The phosphate group is first transferred to enzyme I, second to the histidine-containing phosphocarrier protein HPr, and then to one of a number of sugar-specific enzymes II, The structures of several HPrs and enzymes IIA are known, Here we report the structure of the N-terminal half of enzyme I from Escherichia coli (EIN), Results: The crystal structure of EIN (MW similar to 30 kDa) has been determined and refined at 2.5 Angstrom resolution, It has two distinct structural subdomains; one contains four ex helices arranged as two hairpins in a claw-like conformation, The other consists of a beta sandwich containing a three-stranded antiparallel beta sheet and a four-stranded parallel beta sheet, together with three short alpha helices. Plausible models of complexes between EIN and HPr can be made without assuming major structural changes in either protein, Conclusions: The alpha/beta subdomain of EIN is topologically similar to the phospho-histidine domain of the enzyme pyruvate phosphate dikinase, which is phosphorylated by PEP on a histidyl residue but does not interact with HPr, It is therefore likely that features of this subdomain are important in the autophosphorylation of enzyme I. The helical subdomain of EIN is not found in pyruvate phosphate dikinase; this subdomain is therefore more likely to be involved in phosphoryl transfer to HPr. C1 NIDDK,MOL BIOL LAB,BETHESDA,MD 20892. NHLBI,LAB BIOCHEM GENET,BETHESDA,MD 20892. NR 26 TC 109 Z9 110 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD JUL 15 PY 1996 VL 4 IS 7 BP 861 EP 872 DI 10.1016/S0969-2126(96)00092-5 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UZ434 UT WOS:A1996UZ43400012 PM 8805571 ER PT J AU Lew, AM Brady, JL Silva, A Coligan, JE Georgiou, HM AF Lew, AM Brady, JL Silva, A Coligan, JE Georgiou, HM TI Secretion of CTLA4Ig by an SV40 T antigen-transformed islet cell line inhibits graft rejection against the neoantigen SO TRANSPLANTATION LA English DT Article ID INVIVO; ACTIVATION; CTLA-4; MOUSE; NOD; TRANSPLANTATION; EXPRESSION; MOLECULE; SURVIVAL; B7/BB1 AB In a model of transplantation rejection, we tested whether a graft manipulated to secrete an immunomodulator could protect itself from immune destruction, thus waiving the need for administration of exogenous immunosuppressants to the recipient, An insulinoma cell line, NIT, having the nonobese diabetic (NOD) genotype but also expressing the SV40 large T antigen, was transfected with CTLA4Ig in an attempt to block the CD28/B7 costimulatory pathway between antigen-presenting cells and T lymphocytes near the site of the graft. The SV40 T antigen is potent at inducing graft rejection, NIT.CTLA4Ig and control transfectants were transplanted subcutaneously into young NOD mice to determine whether CTLA4Ig secretion would abet the survival of the insulinoma graft, CTLA4Ig protein was secreted abundantly in vitro (3-5 mu g/ml) and this phenotype was maintained in vivo. Tumor growth was monitored visibly, by palpation, by measuring blood glucose levels, and by death of the host from hypoglycemia caused by unregulated insulin production of the growing insulinoma. Cell growth was similar for NIT.CTLA4Ig and control transfectants in immunodeficient mice (nude, irradiated, or SCID mice), indicating that there was no intrinsic growth advantage of the NIT.CTLA4Ig cells. In immunocompetent NOD mice, however, the survival/growth of the NIT.CTLA4Ig graft was significantly better than that of the controls. Histopathology was consistent with this finding, Donor-specific second-set grafts were acutely rejected, indicating that tolerance was not induced. CTLs were generated even when the graft secreted CTLA4Ig; there was no clear difference in in vitro immune responses generated by NIT.CTLA4Ig and control cells. We conclude that blockade of the B7 costimulation pathway by graft manipulation can contribute to transplantation success. C1 NIAID,NIH,MOLEC STRUCT LAB,ROCKVILLE,MD 20852. RP Lew, AM (reprint author), ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,PARKVILLE,VIC 3050,AUSTRALIA. RI Lew, Andrew/C-7248-2013; Georgiou, Harry/C-7143-2008 OI Lew, Andrew/0000-0002-2198-8164; Georgiou, Harry/0000-0003-0553-9489 NR 31 TC 19 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 1996 VL 62 IS 1 BP 83 EP 89 DI 10.1097/00007890-199607150-00017 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UX685 UT WOS:A1996UX68500017 PM 8693551 ER PT J AU Quinn, TC AF Quinn, TC TI Global burden of the HIV pandemic SO LANCET LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; PREVALENCE; AFRICA; WOMEN; AIDS; RISK AB Within the global pandemic of HIV infection there are many different epidemics, each with its own dynamics and each influenced by many factors including time of introduction of the virus, population density, and cultural and social issues. Effective management strategies depend on knowledge of all these factors. By the year 2000, WHO projections are that 26 million persons will be infected with HIV, more than 90% of whom will be in developing countries. io control AIDS, countries must not only promote changes in individual behaviour but also address social issues such as unemployment, rapid urbanisation, migration, and the status of women. C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. RP Quinn, TC (reprint author), NIAID,BALTIMORE,MD 21205, USA. RI Quinn, Thomas/A-2494-2010 NR 50 TC 217 Z9 223 U1 1 U2 10 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 13 PY 1996 VL 348 IS 9020 BP 99 EP 106 DI 10.1016/S0140-6736(96)01029-X PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UW673 UT WOS:A1996UW67300014 PM 8676726 ER PT J AU Felsenfeld, G AF Felsenfeld, G TI Chromatin unfolds SO CELL LA English DT Review ID LOCUS-CONTROL REGION; NUCLEOSOME DISRUPTION; GENE-EXPRESSION; YEAST; TRANSCRIPTION; COMPLEX; BINDING; REPRESSION; TELOMERE; DNA RP Felsenfeld, G (reprint author), NIDDK,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 52 TC 244 Z9 246 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 12 PY 1996 VL 86 IS 1 BP 13 EP 19 DI 10.1016/S0092-8674(00)80073-2 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UX934 UT WOS:A1996UX93400004 PM 8689680 ER PT J AU Porter, JA Ekker, SC Park, WJ vonKessler, DP Young, KE Chen, CH Ma, Y Woods, AS Cotter, RJ Koonin, EV Beachy, PA AF Porter, JA Ekker, SC Park, WJ vonKessler, DP Young, KE Chen, CH Ma, Y Woods, AS Cotter, RJ Koonin, EV Beachy, PA TI Hedgehog patterning activity: Role of a lipophilic modification mediated by the carboxy-terminal autoprocessing domain SO CELL LA English DT Article ID MEMBRANE-PROTEINS; DROSOPHILA-EMBRYO AB Autocatalytic processing mediated by the carboxyterminal domain of the hedgehog (hh) protein precursor (Hh) generates an amino-terminal product that accounts for all known signaling activity. The role of autoprocessing in biogenesis of the hh signal has been unclear, since a truncated unprocessed protein lacking all carboxy-terminal domain sequences retains signaling activity. Here, we present evidence that the autoprocessing reaction proceeds via an internal thioester intermediate and results in a covalent modification that increases the hydrophobic character of the signaling domain and influences its spatial and subcellular distribution. We demonstrate that truncated unprocessed amino-terminal protein causes embryonic mispatterning, even when expression is localized to cells that normally express Hh, thus suggesting a role for autoprocessing in spatial regulation of hh signaling. This type of processing also appears to operate in the biogenesis of other novel secreted proteins. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. NATL INST HLTH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP Porter, JA (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,HOWARD HUGHES MED INST,BALTIMORE,MD 21205, USA. NR 37 TC 352 Z9 363 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 12 PY 1996 VL 86 IS 1 BP 21 EP 34 DI 10.1016/S0092-8674(00)80074-4 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UX934 UT WOS:A1996UX93400005 PM 8689684 ER PT J AU Frangiskakis, JM Ewart, AK Morris, CA Mervis, CB Bertrand, J Robinson, BF Klein, BP Ensing, GJ Everett, LA Green, ED Proschel, C Gutowski, NJ Noble, M Atkinson, DL Odelberg, SJ Keating, MT AF Frangiskakis, JM Ewart, AK Morris, CA Mervis, CB Bertrand, J Robinson, BF Klein, BP Ensing, GJ Everett, LA Green, ED Proschel, C Gutowski, NJ Noble, M Atkinson, DL Odelberg, SJ Keating, MT TI LIM-kinase1 hemizygosity implicated in impaired visuospatial constructive cognition SO CELL LA English DT Article ID SUPRAVALVULAR AORTIC-STENOSIS; LONG-TERM POTENTIATION; GAMMA-MUTANT MICE; ELASTIN GENE; WILLIAMS-SYNDROME; PROTEIN; TRANSLOCATION; CHROMOSOME-7; HOMEODOMAIN; SEQUENCES AB To identify genes important for human cognitive development, we studied Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families with a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest deletion (83.6 kb) revealed two genes, elastin (ELN) and LIM-kinase-1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in impaired visuospatial constructive cognition. C1 UNIV UTAH, HLTH SCI CTR, ECCLES INST HUMAN GENET, SALT LAKE CITY, UT 84112 USA. UNIV UTAH, HLTH SCI CTR, HOWARD HUGHES MED INST, SALT LAKE CITY, UT 84112 USA. UNIV UTAH, HLTH SCI CTR, DIV CARDIOL, SALT LAKE CITY, UT 84112 USA. UNIV UTAH, HLTH SCI CTR, HUNTSMAN CANC INST, DEPT ONCOL SCI, SALT LAKE CITY, UT 84112 USA. UNIV NEVADA, SCH MED, DEPT PEDIAT, LAS VEGAS, NV 89102 USA. UNIV NEVADA, SCH MED, DEPT PATHOL, LAS VEGAS, NV 89102 USA. EMORY UNIV, DEPT PSYCHOL, ATLANTA, GA 30322 USA. INDIANA UNIV, SCH MED, DEPT PEDIAT, DIV PEDIAT CARDIOL, INDIANAPOLIS, IN 46202 USA. NATL INST HLTH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. UNIV LONDON, INST NEUROL, DEPT CLIN NEUROL, LONDON WC1N 3BG, ENGLAND. RP UNIV UTAH, HLTH SCI CTR, DEPT HUMAN GENET, SALT LAKE CITY, UT 84112 USA. RI Toland, Amanda/E-4202-2011; Robinson, Byron/G-6144-2012 OI Robinson, Byron/0000-0003-2618-5771 FU NHLBI NIH HHS [R01 HL4807]; NICHD NIH HHS [R01 HD029957, R01 HD29957]; NINDS NIH HHS [R01 NS035102, R01 NS35102]; Wellcome Trust NR 50 TC 366 Z9 374 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JUL 12 PY 1996 VL 86 IS 1 BP 59 EP 69 DI 10.1016/S0092-8674(00)80077-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UX934 UT WOS:A1996UX93400008 PM 8689688 ER PT J AU Grewal, SIS Klar, AJS AF Grewal, SIS Klar, AJS TI Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis SO CELL LA English DT Article ID MATING-TYPE REGION; SWITCHING GENE SWI6; SCHIZOSACCHAROMYCES-POMBE; TRANSCRIPTIONAL STATES; MEIOTIC RECOMBINATION; EXPRESSION; LOCI; CASSETTES; CHROMATIN; METHYLATION AB Inheritance of the active and inactive states of gene expression by individual cells is crucial for development. In fission yeast, mating-type region consists of three loci called mat1, mat2, and mat3. Transcriptionally silent mat2 and mat3 loci are separated by a 15 kb interval, designated the K-region, and serve as donors of information for transcriptionally active mat1 interconversion. In a strain carrying replacement of 7.5 kb of the K-region with the ura4 gene, we discovered that ura4 silencing and efficiency of mating-type switching were covariegated and were regulated by an epigenetic mechanism. Genetic analyses demonstrated that epigenetic states were remarkably stable not only in mitosis but also in meiosis and were linked to the mating-type region. This study indicates that different epigenetic states are heritable forms of chromatin organization at the mat region. RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, GENE REGULAT & CHROMOSOME BIOL LAB, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-46000] NR 39 TC 154 Z9 158 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JUL 12 PY 1996 VL 86 IS 1 BP 95 EP 101 DI 10.1016/S0092-8674(00)80080-X PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UX934 UT WOS:A1996UX93400011 PM 8689692 ER PT J AU Barlow, C Hirotsune, S Paylor, R Liyanage, M Eckhaus, M Collins, F Shiloh, Y Crawley, JN Ried, T Tagle, D WynshawBoris, A AF Barlow, C Hirotsune, S Paylor, R Liyanage, M Eckhaus, M Collins, F Shiloh, Y Crawley, JN Ried, T Tagle, D WynshawBoris, A TI Atm-deficient mice: A paradigm of ataxia telangiectasia SO CELL LA English DT Article ID WILD-TYPE P53; DOUBLE-STRAND BREAKS; CELL-CYCLE; P53-DEFICIENT MICE; GENE AMPLIFICATION; MOLECULAR ANALYSIS; GAMMA-IRRADIATION; DNA; RADIATION; TRANSLOCATION AB A murine model of ataxia telangiectasia was created by disrupting the Atm locus via gene targeting. Mice homozygous for the disrupted Atm allele displayed growth retardation, neurologic dysfunction, male and female infertility secondary to the absence of mature gametes, defects in T lymphocyte maturation, and extreme sensitivity to gamma-irradiation. The majority of animals developed malignant thymic lymphomas between 2 and 4 months of age. Several chromosomal anomalies were detected in one of these tumors. Fibroblasts from these mice grew slowly and exhibited abnormal radiation-induced G1 checkpoint function. Atm-disrupted mice recapitulate the ataxia telangiectasia phenotype in humans, providing a mammalian model in which to study the pathophysiology of this pleiotropic disorder. C1 NATL INST HLTH,NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,BETHESDA,MD 20892. NATL INST HLTH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. NIMH,EXPTL THERAPEUT BRANCH,SECT BEHAV NEUROPHARMACOL,NATL INST HLTH,BETHESDA,MD 20892. NATL INST HLTH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,IL-69978 RAMAT AVIV,ISRAEL. RP Barlow, C (reprint author), NATL INST HLTH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892, USA. NR 69 TC 1033 Z9 1040 U1 4 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 12 PY 1996 VL 86 IS 1 BP 159 EP 171 DI 10.1016/S0092-8674(00)80086-0 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UX934 UT WOS:A1996UX93400017 PM 8689683 ER PT J AU Feng, JF Rhee, SG Im, MJ AF Feng, JF Rhee, SG Im, MJ TI Evidence that phospholipase delta 1 is the effector in the G(h) (transglutaminase II)-mediated signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-SUBUNITS; C ISOZYMES; G-PROTEIN; ACTIVATION; PURIFICATION; RECONSTITUTION; BINDING; FAMILY; ALPHA(1)-ADRENOCEPTOR; MEDIATOR AB A new class of GTP-binding protein transglutaminase II (G(h)) couples to a 69 kDa phospholipase C (PLC). An 8-amino acid region (LeU(665)-Lys(672)) of the alpha-subunit of G(h) (G alpha(h)) is involved in interaction and activation of PLC, an observation that has now been used to characterize the 69-kDa PLC further. A 20-amino acid peptide 673 corresponding to Leu(654)-Leu(673) of G alpha(h) was used to prepare an affinity resin. On incubation with a partially purified PLC preparation from rat liver membranes, the affinity resin-bound similar to 69- and 85-kDa proteins were recognized by an antibody to the 69-kDa PLC. Both purified 69-kDa PLC and PLC-delta 1 bound to the affinity resin; moreover, antibodies to PLC-delta 1 recognized the 69-kDa PLC, and antibodies to the 69 kDa PLC recognized PLC-delta 1. A synthetic peptide corresponding to LeU(661)-Lys(672) of G alpha(h) inhibited the binding of PLC-delta 1 to the affinity resin and also stimulated PLC-delta 1. Reconstitution of PLC-delta 1 with GTP gamma S (guanosine 5'-3-O-(thio)triphosphate)-activated G(h) resulted in activation of PLC-delta 1. Antibodies to G alpha(h) also coimmunoprecipitated PLC-delta 1 upon activation of G(h). These findings indicate that PLC-delta 1 is the effector of G(h)-mediated signaling. C1 CLEVELAND CLIN FDN,RES INST,DEPT MOLEC CARDIOL FFB37,CLEVELAND,OH 44195. NHLBI,LAB CELL SIGNALING,NIH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM45985] NR 26 TC 150 Z9 152 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 12 PY 1996 VL 271 IS 28 BP 16451 EP 16454 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX126 UT WOS:A1996UX12600006 PM 8663582 ER PT J AU Gao, BC Eisenberg, E Greene, L AF Gao, BC Eisenberg, E Greene, L TI Effect of constitutive 70-kDa heat shock protein polymerization on its interaction with protein substrate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR CHAPERONE BIP; UNCOATING ATPASE; COATED VESICLES; CLATHRIN; DISSOCIATION; GRP78 AB Constitutive 70-kDa heat shock protein (hsc70) is a mixture of monomers and oligomers in ADP, while in ATP it is monomeric unless certain DnaJ homologs are present which induce hsc70 to form large polymers in an ATP-dependent reaction. A key question regarding polymerized hsc70 is whether it is able to bind protein substrates. Polymerized BiP, the hsc70 present in the endoplasmic reticulum, has been found to bind substrates in vitro although substrates appear to bind only to monomeric BiP in vivo. In this study, we investigated whether substrate binds to polymerized cytoplasmic hsc70 in vitro. Although both stoichiometric ATP and high concentrations of cytochrome c peptide monomerized hsc70, direct binding studies provided no evidence that cytochrome c peptide binds to polymerized hsc70. Furthermore, the time course of cytochrome c peptide and clathrin binding to hsc70 suggested that rather than binding to polymerized hsc70, they monomerized it by reducing free monomer, thereby shifting the monomer-polymer equilibrium toward monomer. We conclude that peptide and protein substrates bind at least an order of magnitude more weakly to polymerized hsc70 than to monomer, suggesting that polymerization of hsc70 in vivo, perhaps by DnaJ homologs, may store it in an inactive form. RP Gao, BC (reprint author), NHLBI,CELL BIOL LAB,NIH,BLDG 3,ROOM B1-22,3 CTR DR,MSC,BETHESDA,MD 20892, USA. NR 25 TC 46 Z9 46 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 12 PY 1996 VL 271 IS 28 BP 16792 EP 16797 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX126 UT WOS:A1996UX12600058 PM 8663341 ER PT J AU RamseyEwing, A Moss, B AF RamseyEwing, A Moss, B TI Recombinant protein synthesis in Chinese hamster ovary cells using a vaccinia virus/bacteriophage T7 hybrid expression system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BACTERIOPHAGE-T7 RNA-POLYMERASE; MAMMALIAN-CELLS; VIRUS; GENES AB The vaccinia virus/bacteriophage T7 expression system was adapted to Chinese hamster ovary (CHO) cells, Vaccinia virus undergoes abortive infection in CHO cells, which is characterized by a sharp reduction in protein synthesis at the stage of viral intermediate gene expression. We determined that expression of a T7 promoter-regulated chloramphenicol acetyltransferase gene was at least 20 times more efficient in permissive BS-C-1 than in CHO cells. The encephalomyocarditis virus 5'-untranslated region, which confers cap-independent translatability to mRNA, stimulated recombinant protein synthesis by 10-fold in both cell lines, maintaining the advantage of the BS-C-1 cells over CHO cells, Since the cowpox virus hr gene overcomes vaccinia virus host range restriction in CHO cells, we constructed a recombinant virus that carries an intact hr gene in addition to the T7 RNA polymerase gene, With this virus, synthesis of T7 RNA polymerase was enhanced and production of a recombinant protein occurred in CHO cells at the level observed in permissive cell lines. Extension of the vaccinia virus/bacteriophage T7 expression system to CHO cells should be of wide interest, as these cells have advantages for preparation of recombinant proteins in research and biotechnology. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NR 22 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 12 PY 1996 VL 271 IS 28 BP 16962 EP 16966 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX126 UT WOS:A1996UX12600081 PM 8663285 ER PT J AU Karp, CL Wysocka, M Wahl, LM Ahearn, JM Cuomo, PJ Sherry, B Trinchieri, G Griffin, DE AF Karp, CL Wysocka, M Wahl, LM Ahearn, JM Cuomo, PJ Sherry, B Trinchieri, G Griffin, DE TI Mechanism of suppression of cell-mediated immunity by measles virus SO SCIENCE LA English DT Article ID PERMEABILITY-INCREASING PROTEIN; HUMAN-IMMUNODEFICIENCY-VIRUS; COMPLEMENT-SYSTEM; INFECTED-CELLS; INTERFERON-GAMMA; ACTIVATION; CD46; INDUCTION; HIV-1; INTERLEUKIN-12 AB The mechanisms underlying the profound suppression of cell-mediated immunity (CMI) accompanying measles are unclear. Interleukin-12 (IL-12), derived principally from monocytes and macrophages, is critical for the generation of CMI. Measles virus (MV) infection of primary human monocytes specifically down-regulated IL-12 production. Cross-linking of CD46, a complement regulatory protein that is the cellular receptor for MV, with antibody or with the complement activation product C3b similarly inhibited monocyte IL-12 production, providing a plausible mechanism for MV-induced immunosuppression. CD46 provides a regulatory link between the complement system and cellular Immune responses. C1 WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. PICOWER INST MED RES,MANHASSET,NY 11030. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOLEC MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. RP Karp, CL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21287, USA. FU NIAID NIH HHS [AI01223, AI23047, AI35149] NR 55 TC 434 Z9 437 U1 0 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 12 PY 1996 VL 273 IS 5272 BP 228 EP 231 DI 10.1126/science.273.5272.228 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UW787 UT WOS:A1996UW78700038 PM 8662504 ER PT J AU Leshner, AI AF Leshner, AI TI Molecular mechanisms of cocaine addiction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP Leshner, AI (reprint author), NIDA,ROCKVILLE,MD 20857, USA. NR 3 TC 30 Z9 31 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 11 PY 1996 VL 335 IS 2 BP 128 EP 129 DI 10.1056/NEJM199607113350211 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UW353 UT WOS:A1996UW35300011 PM 8649475 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI Secrecy in research - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Rosenberg, SA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 11 PY 1996 VL 335 IS 2 BP 135 EP 136 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UW353 UT WOS:A1996UW35300028 ER PT J AU Taubenberger, JK Reid, AH Izon, D Boehme, SA AF Taubenberger, JK Reid, AH Izon, D Boehme, SA TI Development and characterization of v-myc/v-raf-transformed murine fetal thymocyte cell lines SO CELLULAR IMMUNOLOGY LA English DT Article ID 14-DAY MOUSE EMBRYOS; BONE-MARROW CELLS; MATURE B-CELLS; RECEPTOR GENES; CHAIN GENES; REARRANGEMENT; EXPRESSION; DIFFERENTIATION; TRANSCRIPTION; MACROPHAGES AB Transformed murine fetal thymocyte cell lines were derived by incubating fetal thymic organ cultures with a v-myc/v-raf-containing retroviral construct in order to model developmental stages within the early triple negative (CD3(-)CD4(-)CD8(-)) thymocyte population. The resulting 10 cell lines had a lymphoid morphology, were all CD44(+), CD90(+), and were triple negative by surface antigen analysis. The cell. lines, however, were distinguishable by differences in the expression of T cell-associated and T cell-specific genes, The CD3 genes were observed to be discoordinately expressed, in that CD3 gamma chain gene expression was detected in 2 cell lines in the absence of CD3 delta and epsilon expression. Expression of the CD3 gamma chain gene was observed in cell Lines without the expression of other T cell-specific genes or T cell receptor rearrangement and may be one of the earliest T cell-specific genes to be expressed. The transcription factor Ikaros was expressed in all 10 cell lines, whereas the transcription factor TCF1 alpha was expressed only in the 2 most differentiated lines. In 8 cell lines, expression of partial TCR beta and/or TCR alpha transcripts was observed by Northern blot. In several lines, expression of rearranged TCR alpha transcripts in the absence of TCR beta transcripts was demonstrated; however, TCR beta DJ rearrangements were observed by Southern blot in all but 1 of these cell lines, Thus, these cell lines, ordered based on the general pattern of additive gene expression observed, may reflect various stages of triple-negative thymocyte differentiation and provide an in vitro mechanism to elucidate some of the molecular events involved in early thymocyte development. (C) 1996 Academic Press, Inc. C1 MONASH UNIV,SCH MED,DEPT PATHOL & IMMUNOL,PRAHRAN,VIC 3181,AUSTRALIA. NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP Taubenberger, JK (reprint author), ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,MOLEC PATHOL DIV,WASHINGTON,DC 20306, USA. NR 28 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL 10 PY 1996 VL 171 IS 1 BP 41 EP 47 DI 10.1006/cimm.1996.0170 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA UY134 UT WOS:A1996UY13400007 PM 8754860 ER PT J AU Puri, RK Leland, P Obiri, NI Husain, SR Mule, J Pastan, I Kreitman, RJ AF Puri, RK Leland, P Obiri, NI Husain, SR Mule, J Pastan, I Kreitman, RJ TI An improved circularly permuted interleukin 4-toxin is highly cytotoxic to human renal cell carcinoma cells SO CELLULAR IMMUNOLOGY LA English DT Article ID RECEPTOR-GAMMA-CHAIN; AFFINITY IL-4 RECEPTORS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; FUNCTIONAL COMPONENT; TUMOR-CELLS; EXPRESSION; GROWTH; INHIBITION; BINDING AB We have previously demonstrated that a chimeric protein composed of human IL-4 and Pseudomonas exotoxin, termed IL4-PE(4E), is cytotoxic to primary cells derived from human renal cell carcinoma (RCC). To improve the cytotoxicity of IL4-toxins such as IL4-PE(4E) and IL4-PE38KDEL to IL-4 receptor (IL-4R) positive tumor cells, a circularly permutated chimeric toxin was prepared by fusing a truncated PE gene encoding PE38KDEL 3' to a circularly permutated IL-4 mutant gene encoding IL4 amino acids 38-129, the linker GGNGG, and IL4 amino acids 1-37. The resulting chimeric protein, termed IL4(38-37)-PE38KDEL, was tested on five RCC cell lines and its cytotoxicity was compared to that of the native IL4-toxins IL4-PE(4E) and IL4-PE38KDEL. IL4(38-37)-PE38KDEL was found to be 5 to 10 times more cytotoxic to all cell cultures tested compared to either native IL4-toxin. The cytotoxic activity of IL4(38-37)-PE38KDEL was competable by excess IL4 and was confirmed by clonogenic assay. IL4(38-37)-PE38KDEL bound to IL-4R on RCC cells with 6- to 12-fold higher affinity than IL4-PE38KDEL or IL4-PE(4E), RCC tumor cells were found to lack the common gamma chain (gamma(c)) of the IL-4R reported to be present on immune cells. The stable transfection of RCC cells with the gamma(c), chain gene did not significantly change their sensitivity to IL4(38-37)-PE38KDEL, Taken together, our results indicate that the CPIL4-toxin IL4(38-37)-PE38KDEL is highly cytotoxic to human RCC cells due to increased binding affinity to IL-4R while it is not cytotoxic or slightly cytotoxic to T and B cells, monocytic cell. lines, and fresh resting or activated bone marrow-derived cells. The gamma(c) does not seem to increase the internalization rate and/or processing of IL4-toxins in RCC cells, CPIL4-toxin may be a useful agent for the treatment of human RCC. (C) 1996 Academic Press, Inc. C1 UNIV MICHIGAN,DEPT SURG,ANN ARBOR,MI 48109. NCI,MOLEC BIOL LAB,DIV CANC BIOL,NIH,BETHESDA,MD 20892. RP Puri, RK (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,LAB MOLEC TUMOR BIOL,NIH,BLDG 29B,BETHESDA,MD 20892, USA. NR 36 TC 38 Z9 39 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL 10 PY 1996 VL 171 IS 1 BP 80 EP 86 DI 10.1006/cimm.1996.0176 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA UY134 UT WOS:A1996UY13400013 PM 8660841 ER PT J AU Paliogianni, F Boumpas, DT AF Paliogianni, F Boumpas, DT TI Prostaglandin E(2) inhibits the nuclear transcription of the human interleukin 2, but not the IL-4, gene in human T cells by targeting transcription factors AP-1 and NF-AT SO CELLULAR IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; ACTIVATION; RECEPTOR; CAMP; EXPRESSION; BINDING; PROTEIN; INVITRO; PROLIFERATION; SUPPRESSION AB Prostaglandin E(2) (PGE(2)) release from activated macrophages and/or stimulation of T cells is associated with cAMP formation and activation of protein kinase A (PKA). cAMP inhibits Th1- but not Th2-cytokine production and may influence the nature of the immune response to a given antigen. Using DNA transfection and electrophoretic mobility shift assays (EMSA), we have examined the mechanisms for the transcriptional regulation of human IL-2 and IL-4 genes by PGE(2). Stimulation of Jurkat cells with ionomycin and PMA in the presence of PGE(2) inhibited the IL-2- but not the IL-4-promoter activity. In EMSAs, nuclear extracts from primary human T cells stimulated with ionomycin and phorbol esters in the presence of PGE(2) demonstrated decreased binding at the AP-1 and NF-AT sites of the human IL-2 promoter; binding to the OCT-1 and NF-kappa B sites was not affected. These results suggest that cAMP regulates IL-2 production in human T cells by a transcriptional mechanism which involves discrete transactivating pathways for IL-2-promoter activation. (C) 1996 Academic Press, Inc. RP Paliogianni, F (reprint author), NIDDK,KIDNEY DIS SECT,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 40 TC 36 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL 10 PY 1996 VL 171 IS 1 BP 95 EP 101 DI 10.1006/cimm.1996.0178 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA UY134 UT WOS:A1996UY13400015 PM 8660843 ER PT J AU Wang, X Bornslaeger, EA Haub, O TomiharaNewberger, C Lonberg, N Dinulos, MB Disteche, CM Copeland, N Gilbert, DJ Jenkins, NA Lacy, E AF Wang, X Bornslaeger, EA Haub, O TomiharaNewberger, C Lonberg, N Dinulos, MB Disteche, CM Copeland, N Gilbert, DJ Jenkins, NA Lacy, E TI A candidate gene for the amnionless gastrulation stage mouse mutation encodes a TRAF-related protein SO DEVELOPMENTAL BIOLOGY LA English DT Article ID NECROSIS-FACTOR RECEPTOR; GERM LAYER FORMATION; INSERTIONAL MUTATION; EMBRYONIC LETHALITY; CYTOPLASMIC DOMAIN; TRANSGENIC MICE; ALPHA-3 DOMAIN; CD40; ORGANIZATION; SUPERFAMILY AB We report the identification of a new recessive prenatal lethal insertional mutation, amnionless (amn). amn mutant embryos first appear abnormal during the Early Streak stage, between E6.5 and E7.0, when they initiate mesoderm production. Subsequently, the amn mutants become developmentally arrested between the Mid and Late Streak stages of gastrulation and they die and are resorbed between E9.5 and E10.5. While extraembryonic structures, including the chorion, yolk sac blood islands, and allantois appear to develop normally, the small embryonic ectoderm remains undifferentiated and generates no amnion. In addition, the embryonic mesoderm that is produced does not become organized into node, notochord, and somites and there is no morphological evidence of neural induction. Interspecific backcross and fluorescence in situ hybridization analyses map the transgene insertion, and thus the amn mutation, to the distal region of mouse chromosome 12, which has synteny with human chromosome 14q32. A gene encoding a 7.5-kb transcript has been identified at a junction between the integrated transgene and host chromosome 12 sequences that meets three criteria expected of a candidate amn gene. This gene maps to the site of transgene insertion; it is transcribed during gastrulation, and its expression is disrupted in amn mutant embryos. Nucleotide sequencing studies show that the 567 amino acid protein encoded by the 7.5-kb transcript is a member of the newly defined family of putative signal transducing proteins, TRAFs, that associate with the cytoplasmic domains of members of the tumor necrosis factor (TNF) receptor superfamily. Thus, we have named the gene encoding the 7.5-kb transcript TRAFamn. TRAFamn is identical to a recently reported protein (CD40bp, CAP-1, CRAF1, LAP1) that can bind the cytoplasmic domains of CD40 and the lymphotoxin beta receptor (LT beta R), both of which are known members of the TNF receptor superfamily. The implications of these findings regarding a possible role for the TNF receptor superfamily during gastrulation are discussed. (C) 1996 Academic Press, Inc. C1 MEM SLOAN KETTERING CANC CTR,PROGRAM MOL BIOL,NEW YORK,NY 10021. CORNELL UNIV,GRAD SCH MED SCI,ITHACA,NY 14853. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NIAID NIH HHS [AI30502]; NICHD NIH HHS [HD20919]; NIGMS NIH HHS [GM 15773] NR 63 TC 23 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 10 PY 1996 VL 177 IS 1 BP 274 EP 290 DI 10.1006/dbio.1996.0162 PG 17 WC Developmental Biology SC Developmental Biology GA VA136 UT WOS:A1996VA13600023 PM 8660894 ER PT J AU Gallo, CJ Jones, TLZ Aragay, AM Jaffe, LA AF Gallo, CJ Jones, TLZ Aragay, AM Jaffe, LA TI Increased expression of alpha(q) family G-proteins during oocyte maturation and early development of Xenopus laevis SO DEVELOPMENTAL BIOLOGY LA English DT Article ID PHOSPHOLIPASE-C BETA; CALCIUM-RELEASE; EGG ACTIVATION; INOSITOL TRISPHOSPHATE; SEQUENCE DETERMINATION; MUSCARINIC RECEPTOR; PLATELET MEMBRANES; MOLECULAR-CLONING; GAMMA-SUBUNITS; MESSENGER-RNAS AB G-proteins of the alpha(q) family link extracellular stimulation of plasma membrane receptors to phospholipase C and consequently to intracellular Ca2+ release. Because they might function in initiating Ca2+ release at fertilization, we examined G alpha(q) family proteins in oocytes and eggs of Xenopus laevis. Three members of this protein family were identified by immunoblotting and antisense depletion. These proteins are barely detectable in the immature oocyte, but undergo a 6-fold increase in amount during oocyte maturation. This increase in G alpha(q) family protein expression correlates with the acquisition, during oocyte maturation, of the ability to release Ca2+ at fertilization (Schlichter and Elinson, 1981, Dev. Biol. 83, 33-41). In contrast, amounts of G alpha(s) and G alpha(i3) are constant during maturation. We also examined the amounts of G alpha(q), G alpha(s), and G alpha(i3) proteins during early development. While amounts of G alpha(s) and G alpha(i3) show little or no change, G alpha(q) family protein expression increases 27-fold between the egg and neurula stages, suggesting that these proteins may be important in initiating Ca2+ release during early development. (C) 1996 Academic Press, Inc. C1 UNIV CONNECTICUT,CTR HLTH,DEPT PHYSIOL,FARMINGTON,CT 06032. NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. CALTECH,DIV BIOL 147 75,PASADENA,CA 91125. FU NICHD NIH HHS [HD-14939] NR 47 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 10 PY 1996 VL 177 IS 1 BP 300 EP 308 DI 10.1006/dbio.1996.0164 PG 9 WC Developmental Biology SC Developmental Biology GA VA136 UT WOS:A1996VA13600025 PM 8660896 ER PT J AU Wang, MH Dlugosz, AA Sun, Y Suda, T Skeel, A Leonard, EJ AF Wang, MH Dlugosz, AA Sun, Y Suda, T Skeel, A Leonard, EJ TI Macrophage-stimulating protein induces proliferation and migration of murine keratinocytes SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; MOUSE EPIDERMAL-CELLS; AMINO-ACID-SEQUENCE; TYROSINE KINASE; MET PROTOONCOGENE; FACTOR RECEPTORS; SCATTER FACTOR; TERMINAL DIFFERENTIATION; MOLECULAR-CLONING; EPITHELIAL-CELLS AB Macrophage stimulating protein (MSP) is a chemotactic factor for murine peritoneal macrophages. The receptor for human MSP was recently identified as the ron gene product, a transmembrane protein tyrosine kinase cloned from a human keratinocyte cDNA library. Here we report that MSP induced proliferation of murine primary keratinocytes and established keratinocyte cell lines in a concentration-dependent manner. The growth efficacy of MSP was comparable to that of epidermal growth factor and keratinocyte growth factor. In three of four cell lines tested in a chemotaxis chamber, MSP also stimulated migration of keratinocytes on a collagen type IV substratum. The action of MSP was mediated by specific binding of MSP to the STK gene product, a murine homologue of the RON MSP receptor. Binding of MSP to keratinocyte STK induced phosphorylation of the 150 kDa STK beta chain. Herbimycin A, a protein tyrosine kinase inhibitor, blocked MSP-mediated phosphorylation of the STK receptor as well as proliferation of keratinocytes, suggesting the importance of tyrosine kinase activity for transduction of the message delivered by MSP. Previously, the only known target cell for MSP was the resident peritoneal macrophage. These studies establish the keratinocyte as a new target cell for MSP. The action of MSP on keratinocytes may have implications for tissue repair, wound healing, and tumor growth. (C) 1996 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FT DETRICK,MD 21702. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. KUMAMOTO UNIV,SCH MED,DEPT CELL DIFFERENTIAT,INST MOL EMBRYOL & GENET,KUMAMOTO 860,JAPAN. RP Wang, MH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FT DETRICK,MD 21702, USA. RI Suda, Toshio/H-6761-2013 OI Suda, Toshio/0000-0001-7540-1771 NR 66 TC 88 Z9 89 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 10 PY 1996 VL 226 IS 1 BP 39 EP 46 DI 10.1006/excr.1996.0200 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UX592 UT WOS:A1996UX59200005 PM 8660937 ER PT J AU Johnson, SW Shen, DW Pastan, I Gottesman, MM Hamilton, TC AF Johnson, SW Shen, DW Pastan, I Gottesman, MM Hamilton, TC TI Cross-resistance, cisplatin accumulation, and platinum-DNA adduct formation and removal in cisplatin-sensitive and -resistant human hepatoma cell lines SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN OVARIAN-CANCER; L1210 LEUKEMIA-CELLS; CARCINOMA CELLS; CIS-DIAMMINEDICHLOROPLATINUM(II) ACCUMULATION; AMPHOTERICIN-B; REPAIR; GENE; MODULATION; MECHANISM; CYTOTOXICITY AB The BEL7404 human hepatoma cell line was selected in vitro for primary cisplatin resistance. A panel of four cisplatin-resistant sublines were generated which exhibited resistance to cisplatin (up to 34-fold) but were not cross-resistant to adriamycin, taxol, etoposide, or mitomycin C. Further characterization of this panel of cell lines revealed that increased cisplatin resistance was associated with decreased cisplatin accumulation in the selected sublines (up to 14-fold) relative to the parental BEL7404 cell line. A significant reduction in platinum-DNA adduct formation (9-fold) and ribosomal RNA gene-specific interstrand crosslink formation (la-fold) were also observed in the 7404-CP20 cell line. No differences in the rate of platinum efflux from the BEL7404 and 7404-CP20 cell lines were detected following a 4-h loading period, and total platinum-DNA adduct and gene-specific interstrand crosslink removal rates were similar in both cell lines. There were approximately 3-fold more total platinum-DNA adducts present in the BEL7404 cells relative to the 7404-CP20 cells at equitoxic concentrations of cisplatin, suggesting that DNA damage tolerance also contributes to the cisplatin resistance phenotype. Overall, these results indicate that decreased cisplatin accumulation is the major cisplatin resistance mechanism present in the in vitro-selected cell lines. This model system of acquired cisplatin resistance may be valuable in determining the molecular basis for decreased cisplatin uptake and be useful for the study of potential resistance modulators. (C) 1996 Academic Press, Inc. C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. RP Johnson, SW (reprint author), FOX CHASE CANC CTR,DEPT MED ONCOL,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. FU NCI NIH HHS [CA51228] NR 46 TC 47 Z9 47 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 10 PY 1996 VL 226 IS 1 BP 133 EP 139 DI 10.1006/excr.1996.0211 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UX592 UT WOS:A1996UX59200016 PM 8660948 ER PT J AU Baudard, M Flotte, TR Aran, JM Thierry, AR Pastan, I Pang, MG Kearns, WG Gottesman, MM AF Baudard, M Flotte, TR Aran, JM Thierry, AR Pastan, I Pang, MG Kearns, WG Gottesman, MM TI Expression of the human multidrug resistance and glucocerebrosidase cDNAs from adeno-associated vectors: Efficient promoter activity of AAV sequences and in vivo delivery via liposomes SO HUMAN GENE THERAPY LA English DT Article ID ADENOASSOCIATED VIRUS VECTORS; HEMATOPOIETIC PROGENITOR CELLS; HUMAN GAMMA-GLOBIN; GENE-EXPRESSION; P-GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; TARGETED INTEGRATION; NEOMYCIN RESISTANCE; DNA INTEGRATION; MAMMALIAN-CELLS AB Recombinant adeno-associated viruses (rAAV) are attractive tools for gene therapy, We designed plasmids in which the human multidrug resistance gene (hMDR1) cDNA was placed downstream from portions of the 5' end of AAV including either a 234-bp cassette or the entire AAV p5 promoter, The drug-resistant phenotype conferred by the P-glycoprotein (Pgp) efflux pump encoded by the hMDR1 cDNA was used to select NIH-3T3 cells transfected with these plasmids, The 234-bp region alone showed promoter activity similar in strength to that of the entire p5 promoter or the retroviral Harvey murine sarcoma virus long terminal repeat (LTR); this result demonstrates that the 234-bp cassette might be used as a small and efficient promoter in rAAV designed to express large genes approaching the packaging limit of AAV particles, After transfection of AAV-MDR1 vectors, the integration of MDR1 sequences into the host cell genome was demonstrated by fluorescent in situ hybridization (FISH), In addition, Southern analysis of low-molecular-weight DNA extracted from drug-resistant cells grown under continuous selection pressure indicated the persistence of nonintegrated AAV-MDR1 plasmids, Coordinate expression of Pgp and human glucocerebrosidase (hGC) was observed in drug-selected NIH-3T3 cells transfected with a bicistronic vector in which MDR1 cDNA was linked to hGC cDNA via the encephalomyocarditis internal ribosome entry site sequence, Moreover, following a single intravenous injection of the bicistronic vector complexed to cationic liposomes into recipient mice, delivery of MDR1 and GC cDNAs was achieved in all the organs we tested. Our results demonstrate that the efficiency of liposomes as vehicles for in vitro and in vivo gene delivery, the advantages of AAV-vectors, and the use of MDR1 as a selectable marker might be successfully combined in gene therapy protocols. C1 NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,EUDOWOOD DIV PEDIAT RESP SCI,BALTIMORE,MD 21287. EASTERN VIRGINIA MED SCH,CTR PEDIAT RES,NORFOLK,VA 23510. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21287. RI thierry, alain/F-9492-2014 NR 57 TC 30 Z9 31 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 10 PY 1996 VL 7 IS 11 BP 1309 EP 1322 DI 10.1089/hum.1996.7.11-1309 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD320 UT WOS:A1996WD32000001 PM 8818718 ER PT J AU Cornetta, K Srour, EF Moore, A Davidson, A Broun, ER Hromas, R Moen, RC Morgan, RA Rubin, L Anderson, WF Hoffman, R Tricot, G AF Cornetta, K Srour, EF Moore, A Davidson, A Broun, ER Hromas, R Moen, RC Morgan, RA Rubin, L Anderson, WF Hoffman, R Tricot, G TI Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia SO HUMAN GENE THERAPY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; HEMATOPOIETIC PROGENITOR CELLS; HUMAN ADENOSINE-DEAMINASE; STEM-CELLS; MYELOGENOUS LEUKEMIA; METASTATIC MELANOMA; PERIPHERAL-BLOOD; EXPRESSION; MARKING; CONTRIBUTE AB To evaluate whether marrow contributes to relapse after autologous bone marrow transplantation (AuBMT) for acute leukemia, transplanted marrow was marked with the G1N retroviral vector (Genetic Therapy Inc.) containing the neomycin phosphotransferase gene (neo), Between April 1992 and August 1993, 4 patients were transplanted for acute myeloid leukemia (AML) in second complete remission (CR) and 1 patient for acute lymphoid leukemia in first CR, An average of 12.4% (range 5-19%) of transplanted marrow mononuclear cells were exposed to G1N vector for 4 hr, In the vector-treated portion of the marrow, 4.9% of GM-CFU and 3.6% of erythroid burst-forming units (BFU-E) were resistant to G418 in vitro, In the 5 patients, the polymerase chain reaction (PCR) detected the neo sequence on only two occasions after AuBMT, Of 4 patients surviving 1 year after transplantation, only 1 had evidence of gene marked cells by PCR, Two AML patients have relapsed, one of whom had evidence of neo sequences in the bone marrow at day 100 but not at relapse 11 months after AuBMT, The second patient relapsed 18 months after AuBMT but never had PCR evidence of neo sequences before or after relapse, Our results indicate vector-transduced autologous bone marrow from heavily pretreated adults with acute leukemia mark with low efficiency, although vector sequences have been detected in bone marrow and peripheral blood up to 1 year after transplant, Of the 2 relapsed patients, no evidence of vector-marked leukemic blasts have been detected. C1 GENET THERAPY INC,GAITHERSBURG,MD 20878. NIH,MOL HEMATOL BRANCH,BETHESDA,MD 20892. UNIV SO CALIF,GENE THERAPY LABS,LOS ANGELES,CA 90033. RP Cornetta, K (reprint author), INDIANA UNIV,HEMATOL ONCOL SECT,SCH MED,BONE MARROW TRANSPLANTAT PROGRAM,975 W WALNUT ST,INDIANAPOLIS,IN 46202, USA. NR 31 TC 29 Z9 29 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 10 PY 1996 VL 7 IS 11 BP 1323 EP 1329 DI 10.1089/hum.1996.7.11-1323 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD320 UT WOS:A1996WD32000002 PM 8818719 ER PT J AU Cole, DJ Wilson, MC Baron, PL OBrien, P Reed, C Tsang, KY Schlom, J AF Cole, DJ Wilson, MC Baron, PL OBrien, P Reed, C Tsang, KY Schlom, J TI Phase I study of recombinant CEA vaccinia virus vaccine with post vaccination CEA peptide challenge SO HUMAN GENE THERAPY LA English DT Article ID CARCINOEMBRYONIC ANTIGEN GENE; EXPRESSION; MELANOMA; IMMUNOTHERAPY; MOLECULE; SAFETY; CELLS C1 HOLLINGS CANC CTR,CHARLESTON,SC. NCI,TUMOR IMMUNOL & BIOL LAB,DBS,BETHESDA,MD 20892. RP Cole, DJ (reprint author), MUSC,DEPT SURG,ROOM 420N CSB 171 ASHLEY AVE,CHARLESTON,SC, USA. NR 41 TC 40 Z9 40 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUL 10 PY 1996 VL 7 IS 11 BP 1381 EP 1394 DI 10.1089/hum.1996.7.11-1381 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD320 UT WOS:A1996WD32000008 PM 8818725 ER PT J AU OBrien, TR Blattner, WA Waters, D Eyster, ME Hilgartner, MW Cohen, AR Luban, N Hatzakis, A Aledort, LM Rosenberg, PS Miley, WJ Kroner, BL Goedert, JJ AF OBrien, TR Blattner, WA Waters, D Eyster, ME Hilgartner, MW Cohen, AR Luban, N Hatzakis, A Aledort, LM Rosenberg, PS Miley, WJ Kroner, BL Goedert, JJ TI Serum HIV-1 RNA levels and time to development of AIDS in the multicenter hemophilia cohort study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VIRUS TYPE-1 INFECTION; CONTROLLED TRIAL; IMMUNODEFICIENCY; PROPORTIONS; ZIDOVUDINE; CELLS AB Objective.-To determine if the long-term incidence of the acquired immunodeficiency syndrome (AIDS) is related to human immunodeficiency virus type 1 (HIV-1) RNA levels measured early in HIV-1 infection. Design.-Epidemiologic cohort study. Setting.-Five hemophilia treatment centers in the United States. Subjects.-A total of 165 subjects with hemophilia and HIV-1 infection (age at HIV-1 seroconversion, 1-66 years) followed from 1979 to 1995. Methods.-The HIV-1 RNA level was measured by polymerase chain reaction over a range of 200 to 1 million or more HIV-1 RNA copies/mL. in archived serum specimens collected 12 to 36 months (median, 27 months) after the estimated date of HIV-1 seroconversion. Kaplan-Meier methods were used to examine the risk of AIDS and proportional hazards models were used to estimate relative hazards. Results.-The HIV-1 RNA values were similar in subjects younger than 17 years at seroconversion (median, 5214 copies/mL) and those 18 to 34 years old (median, 4693 copies/mL), but higher in those 35 years or older (median, 12 069 copies/mL) (P=.02 compared with each younger group). At 10 years after seroconversion, the proportions of subjects with AIDS were 72% among subjects with 100 000 or more HIV-1 RNA copies/mL measured 12 to 36 months after HIV-1 seroconversion (n=9), 52% among subjects with 10 000 to 99 999 copies/mL (n=55), 22% among subjects with 1000 to 9999 copies/mL (n=82), and 0% among subjects with fewer than 1000 copies/mL (n=19) (P<.001). The age-adjusted relative hazard for AIDS for subjects with 10 000 or more copies/mL was 14.3 (95% confidence interval, 1.9-105.6) compared with subjects with fewer than 1000 copies/mL. Conclusions.-The HIV-1 RNA level during early chronic HIV-1 infection is a strong, age-independent predictor of clinical outcome; low revels define persons with a high probability of long-term AIDS-free survival. C1 PRI,FREDERICK,MD. MILTON S HERSHEY MED CTR,HERSHEY,PA. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. CHILDRENS HOSP,NATL MED CTR,WASHINGTON,DC 20010. MT SINAI MED CTR,NEW YORK,NY 10029. UNIV ATHENS,SCH MED,GR-11527 ATHENS,GREECE. NCI,BIOSTAT BRANCH,ROCKVILLE,MD. RES TRIANGLE INST,ROCKVILLE,MD. RP OBrien, TR (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,PUBL HLTH SERV,US DEPT HHS,EPN 434,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [N01-CP-85649] NR 28 TC 266 Z9 269 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 10 PY 1996 VL 276 IS 2 BP 105 EP 110 DI 10.1001/jama.276.2.105 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UV485 UT WOS:A1996UV48500024 PM 8656501 ER PT J AU Karon, JM Rosenberg, PS McQuillan, G Khare, M Gwinn, M Petersen, LR AF Karon, JM Rosenberg, PS McQuillan, G Khare, M Gwinn, M Petersen, LR TI Prevalence of HIV infection in the United States, 1984 to 1992 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; AIDS; BACKCALCULATION AB Objective.-To estimate the number of persons infected with the human immunodeficiency virus (HIV) living in the United States and the change in HIV infection prevalence since 1984. Design.-We estimated HIV prevalence from 3 data sources. We estimated past HIV infection rates from a statistical procedure based on national acquired immunodeficiency syndrome (AIDS) case surveillance data and estimates of the time from HIV infection to AIDS diagnosis. We also analyzed HIV prevalence data from 2 national surveys, a survey of childbearing women and a household survey of current health status. We used other data sources to adjust these survey estimates to include groups not covered in the surveys. Results.-Approximately 0.3% of US residents (650 000-900 000 persons) were infected with HIV in 1992, Approximately 0.6% of men (including adolescent boys greater than or equal to 13 years of age) were infected, including approximately 2% of non-Hispanic black men and 1% of Hispanic men, Approximately 0.1% of women (including adolescent girls greater than or equal to 13 years of age) were infected, including approximately 0.6% of non-Hispanic black women. Approximately half of all infected persons were men who had sex with men, and one fourth were injecting drug users. The prevalence of HIV infection increased from 1984 to 1992, with a greater relative increase among women than men. Conclusions.-The 3 different data sources and methods are consistent in estimating that 650 000 to 900 000 persons were infected with HIV in the United States in 1992. Among adolescents and adults of both sexes, the proportion infected was substantially higher among non-Hispanic blacks and Hispanics than among non-Hispanic whites, HIV-related illness will be a major clinical and public health problem in the United States for years to come. C1 CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,ATLANTA,GA 30333. NCI,NIH,ROCKVILLE,MD. RP Karon, JM (reprint author), CTR DIS CONTROL & PREVENT,DIV HIV AIDS PREVENT,NATL CTR HIV STD & TB PREVENT,MAILSTOP E-48,ATLANTA,GA 30333, USA. NR 35 TC 177 Z9 179 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 10 PY 1996 VL 276 IS 2 BP 126 EP 131 DI 10.1001/jama.276.2.126 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UV485 UT WOS:A1996UV48500027 PM 8656504 ER PT J AU Fauci, AS AF Fauci, AS TI AIDS in 1996 - Much accomplished, much to do SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INFECTION; DISEASE; HIV RP Fauci, AS (reprint author), NIAID,NIH,BLDG 31,ROOM 7A03,MSC 2520,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 10 Z9 10 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 10 PY 1996 VL 276 IS 2 BP 155 EP 156 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UV485 UT WOS:A1996UV48500031 PM 8656508 ER PT J AU Deyton, L AF Deyton, L TI Importance of surrogate markers in evaluation of antiviral therapy for HIV infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL-TRIALS; END-POINTS; AIDS RP Deyton, L (reprint author), NIAID,DIV AIDS,HIV RES BRANCH,NIH,SOLAR BLDG ROOM 2C16,6003 EXECUT BLVD MSC 7620,BETHESDA,MD 20892, USA. NR 28 TC 13 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 10 PY 1996 VL 276 IS 2 BP 159 EP 160 DI 10.1001/jama.276.2.159 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UV485 UT WOS:A1996UV48500033 PM 8656509 ER PT J AU Li, M Dyda, F Benhar, I Pastan, I Davies, DR AF Li, M Dyda, F Benhar, I Pastan, I Davies, DR TI Crystal structure of the catalytic domain of Pseudomonas exotoxin A complexed with a nicotinamide adenine dinucleotide analog: Implications for the activation process and for ADP ribosylation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DIPHTHERIA-TOXIN; ACTIVE-SITE; GLUTAMIC ACID-553; ELONGATION-FACTOR; ASPARTIC-ACID; AERUGINOSA; RESIDUE AB The catalytic, or third domain of Pseudomonas exotoxin A (PEIII) catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, inhibiting protein synthesis. We have determined the structure of PEIII crystallized in the presence of NAD to define the site of binding and mechanism of activation. However, NAD undergoes a slow hydrolysis and the crystal structure revealed only the hydrolysis products, AMP and nicotinamide, bound to the enzyme. To better define the site of NAD binding, we have now crystallized PEIII in the presence of a less hydrolyzable NAD analog, beta-methylene-thiazole-4-carboxamide adenine dinucleotide (beta-TAD), and refined the complex structure at 2.3 Angstrom resolution. There are two independent molecules of PEIII in the crystal, and the conformations of beta-TAD show some differences in the two binding sites. The beta-TAD attached to molecule 2 appears to have been hydrolyzed between the pyrophosphate and the nicotinamide ribose. However, molecule 1 binds to an intact beta-TAD and has no crystal packing contacts in the vicinity of the binding site, so that the observed conformation and interaction with the PEIII most likely resembles that of NAD bound to PEIII in solution. We have compared this complex with the catalytic domains of diphtheria toxin, heat labile enterotoxin, and pertussis toxin, all three of which it closely resembles. C1 NIDDKD, MOLEC BIOL LAB, NIH, BETHESDA, MD 20892 USA. NCI, MOLEC BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 29 TC 84 Z9 86 U1 2 U2 6 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 JUL 9 PY 1996 VL 93 IS 14 BP 6902 EP 6906 DI 10.1073/pnas.93.14.6902 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UW792 UT WOS:A1996UW79200012 PM 8692916 ER PT J AU Choi, TS Fukasawa, K Zhou, RP Tessarollo, L Borror, K Resau, J VandeWoude, GF AF Choi, TS Fukasawa, K Zhou, RP Tessarollo, L Borror, K Resau, J VandeWoude, GF TI The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID XENOPUS-OOCYTES; MEIOTIC MATURATION; SECONDARY OOCYTES; ONCOGENE PRODUCT; STRAIN MICE; MOS; EGGS; PROTOONCOGENE; INVITRO; PHOSPHORYLATION AB Mos is an upstream activator of mitogen-activated protein kinase (MAPK) and, in mouse oocytes, is responsible for metaphase II arrest. This activity has been likened to its function in Xenopus oocytes as a component of cytostatic factor. Thus, Mos-deficient female mice (MOS(-/-)) are less fertile and oocytes derived from these animals fail to arrest at metaphase II and undergo parthenogenetic activation [Colledge, W.H., Carlton, M. B. L., Udy, G. B. & Evans, M. J. (1994) Nature (London) 370, 65-68 and Hashimoto, N., Watanabe, N., Furuta, Y., Tamemoto, H., Sagata, N., Yokoyama, M., Okazaki, K., Nagayoshi, M., Takeda, N., Ikawa, Y. & Aizawa, S. (1994) Nature (London) 370, 68-71]. Here we show that maturing MOS(-/-) oocytes fail to activate MAPK throughout meiosis, while p34(cdc2) kinase activity is normal until late metaphase II when it decreases prematurely. Phenotypically, the first meiotic division of MOS(-/-) oocytes frequently resembles mitotic cleavage or produces an abnormally large polar body. In these oocytes, the spindle shape is altered and the spindle fails to translocate to the cortex, leading to the establishment of an altered cleavage plane. Moreover, the first polar body persists instead of degrading and sometimes undergoes an additional cleavage, thereby providing conditions for parthenogenesis. These studies identify meiotic spindle formation and programmed degradation of the first polar body as new and important roles for the Mos/MAPK pathway. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RUTGERS STATE UNIV,COLL PHARM,DEPT BIOL CHEM,CANC RES LAB,PISCATAWAY,NJ 08855. NR 41 TC 164 Z9 170 U1 1 U2 6 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 JUL 9 PY 1996 VL 93 IS 14 BP 7032 EP 7035 DI 10.1073/pnas.93.14.7032 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UW792 UT WOS:A1996UW79200036 PM 8692939 ER PT J AU Fan, QR Garboczi, DN Winter, CC Wagtmann, N Long, EO Wiley, DC AF Fan, QR Garboczi, DN Winter, CC Wagtmann, N Long, EO Wiley, DC TI Direct binding of a soluble natural killer cell inhibitory receptor to a soluble human leukocyte antigen-Cw4 class I major histocompatibility complex molecule SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CLONES; LYSIS AB Natural killer (NK) cells expressing specific p58 NK receptors are inhibited from lysing target cells that express human leukocyte antigen (HLA)-C class I major histocompatibility complex molecules. To investigate the interaction between p58 NK receptors and HLA-Cw4, the extracellular domain of the p58 NK receptor specific for HLA-Cw4 was overexpressed in Escherichia coli and refolded from purified inclusion bodies. The refolded NK receptor is a monomer in solution. It interacts specifically with HLA-Cw4, blocking the binding of a p58-Ig fusion protein to HLA-Cw4-expressing cells, but does not block the binding of a p58-Ig fusion protein specific for HLA-Cw3 to HLA-Cw3-expressing cells. The bacterially expressed extracellular domain of HLA-Cw4 heavy chain and beta(2)-microglobulin were refolded in the presence of a HLA-Cw4-specific peptide. Direct binding between the soluble p58 NK receptor and the soluble HLA-Cw4-peptide complex was observed by native gel electrophoresis. Titration binding assays show that soluble monomeric receptor forms a 1:1 complex with HLA-Cw4, independent of the presence of ZN(2+). The formation of complexes between soluble, recombinant molecules indicates that HLA-Cw4 is sufficient for specific ligation by the NK receptor and that neither glycoprotein requires carbohydrate for the interaction. C1 HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 27 TC 75 Z9 75 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 JUL 9 PY 1996 VL 93 IS 14 BP 7178 EP 7183 DI 10.1073/pnas.93.14.7178 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UW792 UT WOS:A1996UW79200062 PM 8692965 ER PT J AU Davis, HL McCluskie, MJ Gerin, JL Purcell, RH AF Davis, HL McCluskie, MJ Gerin, JL Purcell, RH TI DNA vaccine for hepatitis B: Evidence for immunogenicity in chimpanzees and comparison with other vaccines SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SURFACE-ANTIGEN PARTICLES; DIRECT GENE-TRANSFER; SYNTHETIC PEPTIDE; IMMUNIZATION; INFECTION; EFFICACY; INVIVO; REGION; CELLS AB Vaccination of two chimpanzees against hepatitis B virus (HBV) by intramuscular injection of plasmid DNA encoding the major and middle HBV envelope proteins induced group-, subtype- and preS2-specific antibodies. These were initially of IgM isotype, and then they were of IgG (predominantly IgG1) isotype, The chimpanzee injected with 2 mg of DNA attained >100 milli-international units/ml of anti-HBs antibody after one injection and 14,000 milli-international units/ml after four injections. A smaller dose (400 mu g) induced lower and transient titers, but a strong anamnestic response occurred 1 year later. Comparison with responses in 23 chimpanzees receiving various antigen-based HBV vaccines suggests that the DNA approach is promising for prophylactic immunization against HBV. C1 UNIV OTTAWA,FAC HLTH SCI,PROGRAM PHYSIOTHERAPY,OTTAWA,ON K1H 8M5,CANADA. UNIV OTTAWA,FAC MED,DEPT PHYSIOL,OTTAWA,ON K1H 8M5,CANADA. GEORGETOWN UNIV,MED CTR,DIV MOL VIROL & IMMUNOL,ROCKVILLE,MD 20852. NIAID,INFECT DIS LAB,NIH,BETHESDA,MD 20892. RP Davis, HL (reprint author), OTTAWA CIVIC HOSP,LOEB MED RES INST,1053 CARLING ST,OTTAWA,ON K1Y 4E9,CANADA. FU NIAID NIH HHS [AI12387, AI26350, N01 AI 45179] NR 36 TC 185 Z9 204 U1 0 U2 2 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 JUL 9 PY 1996 VL 93 IS 14 BP 7213 EP 7218 DI 10.1073/pnas.93.14.7213 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UW792 UT WOS:A1996UW79200068 PM 8692971 ER PT J AU Mushegian, AR Fullner, KJ Koonin, EV Nester, EW AF Mushegian, AR Fullner, KJ Koonin, EV Nester, EW TI A family of lysozyme-like virulence factors in bacterial pathogens of plants and animals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Agrobacterium; virB genes; conjugative DNA transfer; invasion; glycosidase ID TUMEFACIENS TI-PLASMID; AGROBACTERIUM-TUMEFACIENS; VIRD2 PROTEIN; SEQUENCE; REGION; GENES; DNA; LOCALIZATION; CONJUGATION; MUTAGENESIS AB We describe a conserved family of bacterial gene products that includes the VirB1 virulence factor encoded by tumor-inducing plasmids of Agrobacterium spp., proteins involved in conjugative DNA transfer of broad-host-range bacterial plasmids, and gene products that may be involved in invasion by Shigella spp. and Salmonella enterica. Sequence analysis and structural modeling show that the proteins in this group are related to chicken egg white lysozyme and are likely to adopt a lysozyme-like structural fold. Based on their similarity to lysozyme, we predict that these proteins have glycosidase activity. Iterative data base searches with three conserved sequence motifs from this protein family detect a more distant relationship to bacterial and bacteriophage lytic transglycosylases, and goose egg white lysozyme. Two acidic residues in the VirB1 protein of Agrobacterium tumefaciens form a putative catalytic dyad. Each of these residues was changed into the corresponding amide by site-directed mutagenesis. Strains of A. tumefaciens that express mutated VirB1 proteins have a significantly reduced virulence. We hypothesize that many bacterial proteins involved in export of macromolecules belong to a widespread class of hydrolases and cleave beta-1,4-glycosidic bonds as part of their function. C1 UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. OI Mushegian, Arcady/0000-0002-6809-9225 FU NIGMS NIH HHS [GM32618-22A1] NR 49 TC 82 Z9 87 U1 0 U2 4 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 JUL 9 PY 1996 VL 93 IS 14 BP 7321 EP 7326 DI 10.1073/pnas.93.14.7321 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UW792 UT WOS:A1996UW79200088 PM 8692991 ER PT J AU Spatz, M Yasuma, Y Strasser, A McCarron, RM AF Spatz, M Yasuma, Y Strasser, A McCarron, RM TI Cerebral postischemic hypoperfusion is mediated by ET(A) receptors SO BRAIN RESEARCH LA English DT Article DE endothelin; nitric oxide; cerebral ischemia; cerebral blood flow; endothelin(A) receptor ID NITRIC-OXIDE; SUBARACHNOID HEMORRHAGE; IMMUNOREACTIVE ENDOTHELIN-1; CEREBROSPINAL-FLUID; ISCHEMIA; BRAIN; RAT; PHARMACOLOGY; INHIBITION; ANTAGONIST AB Effect of ET(A)-receptor antagonist, BQ123, on postischemic hypoperfusion in the presence or absence of nitric oxide synthetase inhibitor, N omega-nitro-L-arginine (NLA), was investigated in Mongolian gerbils. BQ123 given prior to ischemia reversed the early incomplete recovery of cerebral blood flow observed with NLA without affecting the late postischemic hypoperfusion. Additional postischemic administration of BQ123 also reversed (P < 0.01) the late postischemic hypoperfusion seen in NLA-, N omega-nitro-D-arginine methyl ester- or Ringer's-treated animals. RP Spatz, M (reprint author), NINCDS,STROKE BRANCH,NIH,36 CONVENT DR,MSC 4128,BETHESDA,MD 20892, USA. NR 31 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 8 PY 1996 VL 726 IS 1-2 BP 242 EP 246 DI 10.1016/S0006-8993(96)00409-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA UZ323 UT WOS:A1996UZ32300030 PM 8836568 ER PT J AU Marth, T Fredricks, D Strober, W Relman, DA AF Marth, T Fredricks, D Strober, W Relman, DA TI Limited role for PCR-based diagnosis of Whipple's disease from peripheral blood mononuclear cells SO LANCET LA English DT Letter C1 STANFORD UNIV,DEPT MED,STANFORD,CA 94305. STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. VET ADM HLTH CARE SYST,PALO ALTO,CA. RP Marth, T (reprint author), NIH,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892, USA. NR 5 TC 21 Z9 21 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 6 PY 1996 VL 348 IS 9019 BP 66 EP 67 DI 10.1016/S0140-6736(05)64400-5 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UV923 UT WOS:A1996UV92300061 PM 8691962 ER PT J AU Paolini, R Serra, A Kinet, JP AF Paolini, R Serra, A Kinet, JP TI Persistence of tyrosine-phosphorylated Fc epsilon RI in deactivated cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AFFINITY IGE RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; IMMUNOGLOBULIN-E RECEPTORS; ANTIGEN RECEPTOR; CROSS-LINKING; MAST-CELLS; SIGNAL TRANSDUCTION; RBL-2H3 CELLS; KINASES; DEPHOSPHORYLATION AB Engagement of the high affinity IgE receptor (Fc epsilon RI) with a multimeric antigen leads to immediate tyrosine phosphorylation of its beta and gamma subunits, recruitment, and activation of the tyrosine kinase Syk, and later to cell degranulation, Monovalent hapten treatment reverses these events, resulting in receptor dephosphorylation and an abrupt arrest of cell degranulation, Thus far, it has been assumed that there is a direct linkage between receptor tyrosine phosphorylation, Syk activation and phosphorylation, and cell degranulation. However, we show here that when Fc epsilon RI receptors are crosslinked for extended periods of time, hapten-mediated receptor dephosphorylation is delayed, These receptors, which remain tyrosine-phosphorylated despite the addition of hapten, are progressively targeted to a Triton X-100-insoluble fraction, suggesting their progressive association with the membrane skeleton, In contrast to Fc epsilon RI receptors, hapten-induced Syk dephosphorylation and the consequent arrest of degranulation are not affected by prolonged cross-linking, Thus, some tyrosine-phosphorylated receptors persist in deactivated cells, We propose that, with time, some tyrosine-phosphorylated receptors become unaccessible to phosphatases and, in addition, unable to activate Syk. This inactive status of tyrosine-phosphorylated Fc epsilon RI may be the result of membrane skeleton compartmentalization. However, another population of clustered receptors that includes the ones most recently formed is still immediately sensitive to hapten deactivation, This latter population is critical in maintaining Syk activity and cell degranulation. The shift from a transiently active state of phosphorylated receptors toward an inactive state could be a general mechanism of desensitization also utilized by other antigen receptors. C1 NIAID,MOLEC ALLERGY & IMMUNOL SECT,NIH,ROCKVILLE,MD 20852. NR 41 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1996 VL 271 IS 27 BP 15987 EP 15992 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UW352 UT WOS:A1996UW35200024 PM 8663241 ER PT J AU JabrilCuenod, B Zhang, C Scharenberg, AM Paolini, R Numerof, R Beaven, MA Kinet, JP AF JabrilCuenod, B Zhang, C Scharenberg, AM Paolini, R Numerof, R Beaven, MA Kinet, JP TI Syk-dependent phosphorylation of Shc - A potential link between Fc epsilon RI and the Ras/mitogen-activated protein kinase signaling pathway through Sos and Grb2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; T-CELL ACTIVATION; TYROSINE PHOSPHORYLATION; RBL-2H3 CELLS; RECEPTOR; RAS; TRANSDUCTION; DOMAIN; ASSOCIATION; ENGAGEMENT AB Antigen receptors on T- and B-cells activate has through a signaling pathway that results in the tyrosine phosphorylation of She and the formation of a complex of Shc with the Grb2 adaptor protein. The high affinity receptor for immunoglobulin E (Fc epsilon RI) in cultured mast (RBL-2H3) cells has been reported to function differently. Here we show to the contrary that engagement of Fc epsilon RI with antigen leads to increased tyrosine phosphorylation of Shc and the association of Shc with Grb2 and other proteins (p120 and p140). Like the Fc epsilon RI-mediated activation of the mitogen-activated protein kinase cascade, these responses are dependent on the tyrosine kinase Syk; they are enhanced by overexpression of Syk and are blocked by expression of dominant-negative Syk. Sos is constitutively associated with Grb2 in these cells but dissociates from Shc on stimulation with antigen. These reactions are rapid, reversible, and associated with the activation of Ras. Therefore, the Syk-dependent tyrosine phosphorylation of Shc and its association with Grb2 may provide a pathway through Sos for activation of Ras by Fc epsilon RI. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. NIAID,MOLEC ALLERGY & IMMUNOL SECT,BETHESDA,MD 20892. NR 49 TC 96 Z9 98 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1996 VL 271 IS 27 BP 16268 EP 16272 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UW352 UT WOS:A1996UW35200061 PM 8663278 ER PT J AU Kotian, P Mascarella, SW Abraham, P Lewin, AH Boja, JW Kuhar, MJ Carroll, FI AF Kotian, P Mascarella, SW Abraham, P Lewin, AH Boja, JW Kuhar, MJ Carroll, FI TI Synthesis, ligand binding, and quantitative structure-activity relationship study of 3 beta-(4'-substituted phenyl)-2 beta-heterocyclic tropanes: Evidence for an electrostatic interaction at the 2 beta-position SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACID METHYL-ESTERS; DOPAMINE TRANSPORTER; MUSCARINIC ACTIVITIES; SELECTIVE COMPOUNDS; WAVE-FUNCTIONS; HIGH-AFFINITY; COCAINE; INHIBITION; RECEPTOR; ANALOGS AB A set of 3 beta-(4'-substituted phenyl)-2 beta-heterocyclic tropanes was designed, synthesized, and characterized. We discovered that these compounds can function as bioisosteric replacements for the corresponding WIN 35,065-2 analogs which possess a 2 beta-carbomethoxy group. Several of the compounds showed high affinity and selectivity for the dopamine transporter (DAT) relative to the serotonin and norepinephrine transporters. From the structure-activity relationship study, the 3 beta-(4'-chlorophenyl)-2 beta-(3'-phenylisoxazol-5-yl)tropane (5d) emerged as the most potent and selective compound. The binding data for 2 beta-heterocyclic tropanes were found to show a high correlation with molecular electrostatic potential (MEP) minima near one of the heteroatoms in the 2 beta-substituents, In contrast, low correlations were found for other MEP minima near the 2 beta-substituent as well as for calculated log P or substituent volume. These quantitative structure-activity relationship studies are consistent with an electrostatic contribution to the binding potency of these WIN 35,065-2 analogs at the DAT. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. FU NIDA NIH HHS [DA05477] NR 31 TC 59 Z9 59 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 5 PY 1996 VL 39 IS 14 BP 2753 EP 2763 DI 10.1021/jm960160e PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UW510 UT WOS:A1996UW51000015 PM 8709106 ER PT J AU Liang, BC AF Liang, BC TI Evidence for association of mitochondrial DNA sequence amplification and nuclear localization in human low-grade gliomas SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE mitochondria; glioma; gene amplification ID HUMAN GENOME; INSERTION; TUMOR; GENE AB Gliomas are tumors which have been found to exhibit consistent genetic changes. Recent studies have shown mitochondrial DNA is also altered in these tumors, and include large deletions and gene amplification. Other studies of the mitochondrial genome in cancer have revealed a variety of different alterations, including the localization and insertion of mitochondrial DNA into the nucleus and nuclear genome in HeLa cells and diethylnitrosurea-induced hepatoma cells, Whether these changes are ontogenically early in the multistep pathway to the development of malignancy, or if this phenomenon occurs in human glial tumors is unknown. I sought to study these questions in a panel of unselected primary glial tumors of pathologically low grade, Fifteen tumors were assessed with a mitochondrial cDNA probe with homology to positions 1679-1948, and 2017-2057, All low-grade tumors revealed increases in copy number when compared to a normal brain control, Nuclear suspensions of these tumors were evaluated by fluorescent in situ hybridization (FISH): using the entire mitochondrial genome as a probe after labeling with rhodamine, All tumors showed evidence of mitochondrial sequence localization within the nuclei. A corresponding glioblastoma and two nonnal brain specimens were also evaluated which did not have amplification of the mitochondrial genome; FISH with the mitochondrial probe revealed minimal hybridization signal within the nuclei of these samples. Mitochondrial DNA nuclear localization can be found in primary low-grade brain neoplasms, and is correlated to increases in mitochondrial DNA. C1 NCI,CLIN PHARMACOL BRANCH,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NR 23 TC 31 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUL 5 PY 1996 VL 354 IS 1 BP 27 EP 33 DI 10.1016/0027-5107(96)00004-8 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA UY488 UT WOS:A1996UY48800004 PM 8692203 ER PT J AU Fukamauchi, F Mataga, N Wang, YJ Chuang, DM AF Fukamauchi, F Mataga, N Wang, YJ Chuang, DM TI Differential effects of butyrate and dibutyryl cAMP on mRNA levels of muscarinic acetylcholine receptor subtypes expressed in neurohybrid cell lines SO NEUROSCIENCE LETTERS LA English DT Article DE muscarinic acetylcholine receptor mRNA; butyrate; dibutyryl cAMP; NCB-20; NG108-15; northern blot analysis ID FAMILY AB NCB-20 cells expressed m1- and m4-muscarinic acetylcholine receptor (mAChR) mRNAs, while NG108-15 cells expressed only m4-mAChR mRNA. Butyrate induced a time-dependent increase in the level of m1-mAChR mRNA with no change in the m4-mAChR mRNA level in NCB-20 cells. Similarly, butyrate did not affect the m4-mAChR mRNA level in NG108-15 cells. In contrast, dibutyryl cAMP caused a significant time-dependent decrease in the level of m4-mAChR mRNA in NCB-20 and NG108-15 cells as well as m1-mAChR mRNA in NCB-20 cells. Our results suggest that these two differentiating agents are important physiological regulators of the transcription and/or stability of the mRNA of certain mAChR subtypes expressed in these two neurohybrid cell lines. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. TOKYO MED & DENT UNIV,MED RES INST,DEPT MOL MED SCI,CHIYODA KU,TOKYO 101,JAPAN. RI Mataga, Nobuko /N-5531-2015 OI Mataga, Nobuko /0000-0003-0991-4354 NR 13 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 5 PY 1996 VL 212 IS 1 BP 49 EP 52 DI 10.1016/0304-3940(96)12779-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UX387 UT WOS:A1996UX38700013 PM 8823760 ER PT J AU Bicout, DJ Field, MJ AF Bicout, DJ Field, MJ TI Electron transfer in proteins: A multiple scattering approach to electronic coupling - Reply SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article C1 INST BIOL STRUCT JEAN PIERRE EBEL,LAB DYNAM MOL,F-38027 GRENOBLE 01,FRANCE. NIDDK,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 6 TC 1 Z9 1 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JUL 4 PY 1996 VL 100 IS 27 BP 11505 EP 11506 DI 10.1021/jp960534f PG 2 WC Chemistry, Physical SC Chemistry GA UV312 UT WOS:A1996UV31200044 ER PT J AU Eden, GF VanMeter, JW Rumsey, JM Maisog, JM Woods, RP Zeffiro, TA AF Eden, GF VanMeter, JW Rumsey, JM Maisog, JM Woods, RP Zeffiro, TA TI Abnormal processing of visual motion In dyslexia revealed by functional brain imaging SO NATURE LA English DT Article ID DEVELOPMENTAL DYSLEXIA; CORTEX; ORGANIZATION; COLOR; CONNECTIONS; PERCEPTION; MOVEMENT; VISION AB IT is widely accepted that dyslexics have deficits in reading and phonological awareness(1,2), but there is increasing evidence that they also exhibit visual processing abnormalities that may be confined to particular portions of the visual system(3,4). In primate visual pathways, inputs from parvocellular or magnocellular layers of the lateral geniculate nucleus remain partly segregated in projections to extrastriate cortical areas specialized for processing colour and form versus motion(5-10), In studies of dyslexia, psychophysical(3) and anatomical(4) evidence indicate an anomaly in the magnocellular visual subsystem, To investigate the pathophysiology of dyslexia, we used functional magnetic resonance imaging (fMRI) to study visual motion processing in normal and dyslexic men, In all dyslexics, presentation of moving stimuli failed to produce the same task-related functional activation in area V5/MT (part of the magnocellular visual subsystem) observed in controls, In contrast, presentation of stationary patterns resulted in equivalent activations in V1/V2 and extrastriate cortex in both groups, Although previous studies have emphasized language deficits, our data reveal differences in the regional functional organization of the cortical visual system in dyslexia. C1 NIMH,CHILD PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. NIH,LAB DIAGNOST RADIOL RES,OD,BETHESDA,MD 20892. SENSOR SYST INC,STERLING,VA 20164. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90098. RP Eden, GF (reprint author), NIMH,SECT FUNCT BRAIN IMAGING,NIH,BETHESDA,MD 20892, USA. NR 29 TC 417 Z9 426 U1 6 U2 46 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUL 4 PY 1996 VL 382 IS 6586 BP 66 EP 69 DI 10.1038/382066a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UV473 UT WOS:A1996UV47300054 PM 8657305 ER PT J AU Pichel, JG Shen, LY Sheng, HZ Granholm, AC Drago, J Grinberg, A Lee, EJ Huang, SP Saarma, M Hoffer, BJ Sariola, H Westphal, H AF Pichel, JG Shen, LY Sheng, HZ Granholm, AC Drago, J Grinberg, A Lee, EJ Huang, SP Saarma, M Hoffer, BJ Sariola, H Westphal, H TI Defects in enteric innervation and kidney development in mice lacking GDNF SO NATURE LA English DT Article ID EMBRYONIC STEM-CELLS; LETHALITY; GENE AB GLIAL-CELL-LINE-DERIVED neurotrophic factor (GDNF) has been isolated as a neurotrophic factor for midbrain dopaminergic neurons(1). Because of its neurotrophic activity on a wide range of neuronal populations in vitro and in vivo(2-11), GDNF is being considered as a potential therapeutic agent for neuronal disorders(2,3,12). During mammalian development, it is expressed not only in the nervous system, but also very prominently in the metanephric kidney and the gastrointestinal tract, suggesting possible functions during organogenesis(7,11,13,14). We have investigated the role of GDNF during development by generating a null mutation in the murine GDNF locus, and found that mutant mice show kidney agenesis or dysgenesis and defective enteric innervation. We demonstrate that GDNF induces ureter bud formation and branching during metanephros development, and is essential for proper innervation of the gastrointestinal tract. C1 NIH,LAB MAMMALIAN GENET & DEV,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT BASIC DENT SCI,DENVER,CO 80262. MONASH UNIV,DEPT ANAT,CLAYTON,VIC 3168,AUSTRALIA. UNIV HELSINKI,BIOCTR 1,PROGRAM MOL NEUROBIOL,FIN-00014 HELSINKI,FINLAND. UNIV HELSINKI,BIOCTR 1,PROGRAM DEV BIOL,FIN-00014 HELSINKI,FINLAND. UNIV HELSINKI,CHILDRENS HOSP,LAB PEDIAT PATHOL,FIN-00380 HELSINKI,FINLAND. NR 30 TC 848 Z9 857 U1 0 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUL 4 PY 1996 VL 382 IS 6586 BP 73 EP 76 DI 10.1038/382073a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UV473 UT WOS:A1996UV47300056 PM 8657307 ER PT J AU Kost, RG Straus, SE AF Kost, RG Straus, SE TI Postherpetic neuralgia pathogenesis, treatment, and prevention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID POST-HERPETIC NEURALGIA; VARICELLA-ZOSTER VIRUS; ORAL ACYCLOVIR; TOPICAL CAPSAICIN; NEUROPATHIC PAIN; PSYCHOTROPIC-DRUGS; IMMUNE-RESPONSES; DOUBLE-BLIND; AMITRIPTYLINE; PLACEBO RP Kost, RG (reprint author), NIAID,CLIN INVEST LAB,NIH,MED VIROL SECT,BLDG 10,RM 11N228,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 110 TC 341 Z9 360 U1 0 U2 18 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 4 PY 1996 VL 335 IS 1 BP 32 EP 42 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA UU479 UT WOS:A1996UU47900007 PM 8637540 ER PT J AU Bardin, CW AF Bardin, CW TI The anabolic action of testosterone SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID METABOLISM RP Bardin, CW (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 7 TC 33 Z9 34 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 4 PY 1996 VL 335 IS 1 BP 52 EP 53 DI 10.1056/NEJM199607043350111 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UU479 UT WOS:A1996UU47900012 PM 8637543 ER PT J AU Rutberg, SE Saez, E Glick, A Dlugosz, AA Spiegelman, BM Yuspa, SH AF Rutberg, SE Saez, E Glick, A Dlugosz, AA Spiegelman, BM Yuspa, SH TI Differentiation of mouse keratinocytes is accompanied by PKC-dependent changes in AP-1 proteins SO ONCOGENE LA English DT Article DE AP-1; keratinocytes; protein kinase C; mouse skin; differentiation; c-fos ID TISSUE-SPECIFIC EXPRESSION; KINASE-C-DELTA; EPIDERMAL DIFFERENTIATION; SELECTIVE INHIBITOR; SKIN CARCINOGENESIS; BINDING-PROTEINS; GENE-EXPRESSION; PHORBOL ESTER; CYCLIC-AMP; FOS AB The conversion of cultured basal keratinocytes to the spinous and granular cell phenotypes seen in the skin can be stimulated by raising the levels of extracellular calcium, Here me show that AP-1 DNA binding activity is very low in primary cultures of basal keratinocytes, but that this activity is induced 24-48 h after increasing the concentration of extracellular calcium from 0.05 to 0.12 mM. As such, the induction of AP-1 DNA binding activity correlates with events occurring during the terminal stages of keratinocyte differentiation, Calcium-induced AP-1 DNA binding complexes consist of Pra-1, Fra-2, c-Jun, JunB and JunD and are independent of c-Fos, since the induction of DNA binding activity and the composition of the AP-1 binding complexes are identical in differentiating keratinocytes derived from c-fos null and wild type mice, The formation of calcium-induced AP-1 binding complexes is regulated by protein kinase C (PKC) and requires a functional PKC alpha isozyme, as determined through pharmacological down-modulation of specific PKC isozymes in differentiating keratinocytes, Moreover, PKC activation is required for the increased expression of Fra-2, JunB and JunD in the nucleus of differentiating cells in vitro. This observation provides a link between the obligate activation of PKC during keratinocyte differentiation and the nuclear response required to alter gene expression, In vivo expression patterns suggest that the predominant AP-1 heterodimer in the granular layer consists of Fra-2 and JunB while a JunD and Fra-1 complex predominates the spinous layer of mouse epidermis, These findings suggest distinct functions for different AP-1 proteins in the regulation of events related to keratinocyte maturation. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NR 67 TC 111 Z9 111 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 4 PY 1996 VL 13 IS 1 BP 167 EP 176 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UX319 UT WOS:A1996UX31900019 PM 8700543 ER PT J AU Bhatia, K Raj, A Gutierrez, MI Judde, JG Spangler, G Venkatesh, H Magrath, IT AF Bhatia, K Raj, A Gutierrez, MI Judde, JG Spangler, G Venkatesh, H Magrath, IT TI Variation in the sequence of Epstein Barr virus nuclear antigen 1 in normal peripheral blood lymphocytes and in Burkitt's lymphomas SO ONCOGENE LA English DT Article DE EBV; EBNA-1; Burkitt's lymphoma; mutations; lymphomagenesis ID CELLS; ASSOCIATION; EXPRESSION; TUMORS; EBV AB We have examined sequence variations in the EBNA-1 protein of EBV in normal peripheral blood lymphocytes (PBL) and Burkitt's lymphomas (BL), We find two EBNA-1 strains P (prototype) and V (variant) which differ by 15 amino acids, Each strain has two subtypes defined by the amino acid at position 487 (P-ala, P-thr, V-pro and V-leu), In PBLs from 32 normal individuals, up to three of these subtypes were found in each sample, but the V strain did not occur in the absence of P strain viruses, nor was the V-leu subtype ever observed in normal PBL, In BLs only a single subtype was observed in each tumor, The P-thr and V-leu subtypes were more frequently seen than the P-ala and V-pro subtypes, which occurred in only two and one of the 36 tumor samples respectively, The P-thr was the most commonly observed peripheral blood of both American and as well as in African tumors, However, in 11 of 12 American tumors, the EBNA-1 subtype was V-leu, These data indicate that some EBNA-1 subtypes are more likely to lead to oncogenesis, and one subtype, V-leu, appears only to occur in tumors. RP Bhatia, K (reprint author), NATL CANC INST,LYMPHOMA BIOL SECT,PEDIAT BRANCH,NIH,BLDG 10,ROOM 13N240,10 CTR DR MSC 1928,BETHESDA,MD 20892, USA. NR 20 TC 93 Z9 98 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 4 PY 1996 VL 13 IS 1 BP 177 EP 181 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UX319 UT WOS:A1996UX31900020 PM 8700544 ER PT J AU Stuver, SO Okayama, A Tachibana, N Tsubouchi, H Mueller, NE Tabor, E AF Stuver, SO Okayama, A Tachibana, N Tsubouchi, H Mueller, NE Tabor, E TI HCV infection and liver cancer mortality in a Japanese population with HTLV-I SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HEPATITIS-C VIRUS; HEPATOCELLULAR-CARCINOMA; RISK; CARRIERS AB In a cohort study of human T-lymphotropic virus type 1 (HTLV-1) infection in japan, 10 cases of liver cancer death occurred from 1984 through 1993. To analyze the role of hepatitis C virus (HCV), which has been associated with an increasing incidence of hepatocellular carcinoma (HCC) in Japan, a nested case-control study was performed. Five of the 10 liver cancer cases were positive for antibody to HTLV-1 (anti-HTLV-1). The possible interaction between HCV and HTLV-1 infections in the etiology of HCC was investigated, with each liver cancer case matched to 5 cohort controls by gender, age, serum sample date and anti-HTLV-1 status. Using a matched analysis, odds ratios (OR) were generated for the relationship between HCV serologic status and death from liver cancer. Based on second-generation enzyme immunoassay with confirmation by recombinant immunoblot assay, 8 of 9 cases with adequate serum available (89%) and 9 of 50 (18%) controls were found to be positive for antibody to HCV(anti-HCV). Liver cancer death war highly associated with anti-HCV (matched OR = infinity; p < 0.001). Anti-HTLV-1 seroprevalence war somewhat correlated with HCV infection. However, the high risk of liver cancer death observed for anti-HCV-positive individuals in this population did not vary with respect to whether or not the subjects were also infected with HTLV-1. (C) 1996 Wiley-Liss, Inc. C1 MIYAZAKI MED COLL, DEPT MED 2, MIYAZAKI, JAPAN. OITA PREFECTURAL INST HLTH & ENVIRONM, OITA, JAPAN. NCI, NIH, BETHESDA, MD 20892 USA. RP Stuver, SO (reprint author), HARVARD UNIV, SCH PUBL HLTH, DEPT EPIDEMIOL, 677 HUNTINGTON AVE, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA-38450] NR 17 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 3 PY 1996 VL 67 IS 1 BP 35 EP 37 DI 10.1002/(SICI)1097-0215(19960703)67:1<35::AID-IJC8>3.0.CO;2-0 PG 3 WC Oncology SC Oncology GA UU461 UT WOS:A1996UU46100008 PM 8690522 ER PT J AU Reiter, Y Wright, AF Tonge, DW Pastan, I AF Reiter, Y Wright, AF Tonge, DW Pastan, I TI Recombinant single-chain and disulfide-stabilized Fv-immunotoxins that cause complete regression of a human colon cancer xenograft in nude mice SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; MUCIN; PURIFICATION; CARCINOMA; PROTEINS; ANTIGEN; DOMAINS; TOXINS AB Monoclonal antibody (MAb) 55.1 specifically recognizes an antigen on the surface of human colon adenocarcinoma cells. We constructed recombinant immunotoxins composed of the heavy- and light-chain variable regions of MAb 55.1 fused to a recombinant form of Pseudomonas exotoxin (PE). The heavy-and light-chain variable regions are stabilized by 2 means. One is by a flexible peptide linker to form a single-chain antigen binding protein (scFv) and the second by an interchain disulfide bond engineered between structurally conserved framework regions. These are termed disulfide stabilized Fvs (dsFv). The 2 Fv forms are fused to truncated forms of PE lacking the cell binding domain. The recombinant scFv- and dsFv-immunotoxins were expressed in E. coli and purified to near homogeneity. The scFv- and dsFv-immunotoxins were shown to be specifically cytotoxic to human colon adenocarcinoma cell lines. The scFv-immunotoxin containing PE38KDEL war more active than the immunotoxin containing PE38 with the native carboxyl terminus (REDLK). However, the PE38KDEL immunotoxin is about 2-fold more toxic in mice, and therefore it doer not appreciably increase the therapeutic window in mice. Intravenous administration of the scFv- and dsFv- recombinant immunotoxins caused complete regression of a human colon carcinoma (Colo205) growing subcutaneously in immunodeficient mice. The dsFv-immunotoxin has better antitumor activity compared with its scFv-immunotoxin counterpart. (C) 1996 Wiley-Liss, Inc. C1 NCI, MOLEC BIOL LAB, DIV BASIC SCI, NIH, BETHESDA, MD 20892 USA. ZENECA PHARMACEUT, DEPT CANC RES, MACCLESFIELD SK10 4TG, CHESHIRE, ENGLAND. NR 30 TC 29 Z9 29 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD JUL 3 PY 1996 VL 67 IS 1 BP 113 EP 123 DI 10.1002/(SICI)1097-0215(19960703)67:1<113::AID-IJC19>3.3.CO;2-6 PG 11 WC Oncology SC Oncology GA UU461 UT WOS:A1996UU46100019 PM 8690511 ER PT J AU Weissinger, EM Byrd, LG Henderson, DW Mushinski, JF AF Weissinger, EM Byrd, LG Henderson, DW Mushinski, JF TI Overexpression of v-abl uniquely cooperates with c-myc dysregulation in induction of plasma cell tumors, bypassing the need for T-lymphocytic help and overcoming T-lymphocytic interference SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MURINE PLASMACYTOMA; B-CELLS; RETROVIRUS; MICE; PRISTANE; INDOMETHACIN; INVITRO; SWITCH; VIRUS; GENE AB We have investigated the effects of T lymphocytes on induction of mouse plasma cell tumors. We show that ABL-MYC, a plasmacytomagenic retrovirus that constitutively expresses v-abl and c-myc, is able to induce plasmacytomas in 100% of athymic BALB/c mice, with or without intraperitoneal pristane pretreatment. Other induction regimens are ineffective under these conditions, indicating that the combination of v-abl and c-myc oncogenes is uniquely able to transform plasma cells in mice that are deficient in T lymphocytes. Furthermore, in the absence of pristane, ABL-MYC-infected athymic congenics developed plasmacytomas in half the time required for euthymic BALB/c mice, suggesting that T lymphocytes can have a negative effect and can retard, but not totally inhibit, the outgrowth of plasmacytomas. This phenomenon could not be appreciated in other regimens of plasmacytoma induction, because only ABL-MYC is sufficient to induce plasmacytomas in athymic mice or in euthymic mice in the absence of pristane pretreatment. (C) 1996 Wiley-Liss, Inc. C1 NCI,GENET LAB,BETHESDA,MD 20892. NR 26 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 3 PY 1996 VL 67 IS 1 BP 142 EP 147 DI 10.1002/(SICI)1097-0215(19960703)67:1<142::AID-IJC23>3.3.CO;2-F PG 6 WC Oncology SC Oncology GA UU461 UT WOS:A1996UU46100023 PM 8690515 ER PT J AU Tjandra, N Grzesiek, S Bax, A AF Tjandra, N Grzesiek, S Bax, A TI Magnetic field dependence of nitrogen-proton J splittings in N-15-enriched human ubiquitin resulting from relaxation interference and residual dipolar coupling SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CHEMICAL-SHIFTS; CONSTANTS 3JHN-ALPHA; NUCLEIC-ACIDS; NMR-SPECTRA; PROTEINS; SPECTROSCOPY; RESOLUTION AB One-bond (1)J(NH) couplings have been measured in N-15-enriched human ubiquitin and range from 91.1 to 95.6 Hz. Measurements have been carried out using two different methods and at H-1 frequencies of 360, 500, and 600 MHz. The best method yields a precision of ca 0.02 Hz, and permits reliable measurement of the small changes (<0.3 Hz) in (1)J(NH) Splitting that occur when the magnetic field strength is increased from 8.5 to 14 T. The dependence of the (1)J(NH) splittings on the strength of the static magnetic field originates from two sources: a dynamic frequency shift caused by interference of the N-15 chemical shift anisotropy and the N-15-H-1 dipolar coupling relaxation mechanisms, and a dipolar contribution caused by a small degree of alignment resulting from the anisotropic magnetic susceptibility of the diamagnetic protein. Best fitting of the measured data yields an orientation-independent decrease of 0.11 Hz in the (1)J(NH) splittings at 609 MHz relative to 360 MHZ; in perfect agreement with theoretical predictions for the magnitude of the dynamic frequency shift. When fitting the measured J values to the theoretical model, containing only the dynamic frequency shift and dipolar coupling contributions, the reduced error in the statistical F-test is smaller than one, assuming a 0.02 Hz rms error in the experimental (1)J(NH) splittings. This confirms that the random error in the measured data J(NH) values does not exceed 0.02 Hz, and that effects other than the dipolar coupling and dynamic frequency shift are not detectable. Dependence of the change in (1)J(NH) On the orientation of the N-H bond vector within the molecular frame yields experimentally determined axial and rhombic magnetic shielding susceptibility anisotropies of -2.1 x 10(-28) and 0.7 x 10(-28) cm(3)/molecule, respectively. A small improvement of the fit is observed when the amide proton is positioned at a distance above or below the C-i-1'-N-i-C-i(alpha) plane which is about five times smaller than the out-of-plane distance predicted by ab initio calculations on a dipeptide analog in vacuum. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 37 TC 300 Z9 303 U1 3 U2 33 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 3 PY 1996 VL 118 IS 26 BP 6264 EP 6272 DI 10.1021/ja960106n PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA UV292 UT WOS:A1996UV29200023 ER PT J AU Etcheberrigaray, R Payne, JL Alkon, DL AF Etcheberrigaray, R Payne, JL Alkon, DL TI Soluble beta-amyloid induces Alzheimer's disease features in human fibroblasts and in neuronal tissues SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT Conference on the Current Status of the Calcium Hypothesis of Brain Aging and Alzheimers Disease CY OCT 23-25, 1995 CL HEIDELBERG, GERMANY SP Int Wissenschaftsforum Univ Heidelberg, Bayer AG, Leverkusen DE beta-amyloid; K+ channels; Alzheimer's disease ID POTASSIUM CHANNEL; PROTEIN; CALCIUM; MANIFESTATIONS; TRANSIENTS; PRECURSOR; DONORS AB It has been shown that K+ channels, Cp20 (a 20kD GTP-binding protein), and intracellular calcium release, play a key role in associative memory storage. These same elements have been shown to be altered in fibroblasts from Alzheimer's Disease (AD) patients. In addition, it has been shown that PKC, also implicated in memory storage and closely related to the above mentioned components, is also altered in AD fibroblasts. Moreover, beta-amyloid was capable of inducing an AD-like phenotype for K+ channels and Cp20 in otherwise normal fibroblasts, providing additional evidence for the potential involvement of these components in AD and suggesting a possible pathological consequence of soluble beta-amyloid elevation in AD. Preliminary evidence shows that comparable changes in potassium channel function are also present in human olfactory neuroblasts from AD patients. These results indicate that the observed changes not only occur in peripheral tissues such as fibroblasts, but also in neural tissue, the primary site of AD pathology. C1 NINCDS,NIH,LAB ADAPT SYST,BETHESDA,MD 20892. RP Etcheberrigaray, R (reprint author), GEORGETOWN UNIV,MED CTR,INST COGNIT & COMPUTAT SCI,WASHINGTON,DC 20007, USA. NR 40 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 3 PY 1996 VL 59 IS 5-6 BP 491 EP 498 DI 10.1016/0024-3205(96)00328-1 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UX037 UT WOS:A1996UX03700016 PM 8761337 ER PT J AU Hinck, AP Archer, SJ Qian, SW Roberts, AB Sporn, MB Weatherbee, JA Tsang, MLS Lucas, R Zhang, BL Wenker, J Torchia, DA AF Hinck, AP Archer, SJ Qian, SW Roberts, AB Sporn, MB Weatherbee, JA Tsang, MLS Lucas, R Zhang, BL Wenker, J Torchia, DA TI Transforming growth factor beta 1: Three-dimensional structure in solution and comparison with the X-ray structure of transforming growth factor beta 2 SO BIOCHEMISTRY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; SIDE-CHAIN RESONANCES; CARBON-J-COUPLINGS; PROTEIN STRUCTURES; CRYSTAL-STRUCTURE; SECONDARY STRUCTURE; ENDOTHELIAL-CELLS; PRACTICAL ASPECTS; LARGER PROTEINS; RECEPTOR SYSTEM AB The three-dimensional solution structure of human transforming growth factor beta 1 (TGF-beta 1) has been determined using multinuclear magnetic resonance spectroscopy and a hybrid distance geometry/simulated annealing algorithm. It represents one of the first examples of a mammalian protein structure that has been solved by isotopic labeling of the protein in a eukaryotic cell line and multinuclear NMR spectroscopy. The solution structure of the 25 kDa disulfide-linked TGF-beta 1 homodimer was calculated from over 3200 distance and dihedral angle restraints. The final ensemble of 33 accepted structures had no NOE or dihedral angle violations greater than 0.30 Angstrom and 5.0 degrees, respectively. The RMSD of backbone atoms for the ensemble of 33 structures relative to their mean structure was 1.1 Angstrom when all residues were used in the alignment and 0.7 Angstrom when loop regions were omitted. The solution structure of TGF-beta 1 follows two independently determined crystal structures of TGF-beta 2 (Daopin et al., 1992, 1993; Schlunegger & Grutter, 1992, 1993), providing the first opportunity to examine structural differences between the two isoforms at the molecular level. Although the structures are very similar, with an RMSD in backbone atom positions of 1.4 Angstrom when loop regions are omitted in the alignment and 1.9 Angstrom when all residues are considered, there are several notable differences in structure and flexibility which may be related to function. The dearest example of these is in the p-turn from residues 69-72: the turn type found in the solution structure of TGF-beta 1 falls into the category of type II, whereas that present in the X-ray crystal structure of TGF-beta 2 is more consistent with a type I turn conformation. This may be of functional significance as studies using TGF-beta chimeras and deletion mutants indicate that this portion of the molecule may be important in receptor binding. C1 NIDR,STRUCT MOLEC BIOL UNIT,NIH,BETHESDA,MD 20892. R&D SYST INC,MINNEAPOLIS,MN 55413. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 62 TC 121 Z9 125 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 2 PY 1996 VL 35 IS 26 BP 8517 EP 8534 DI 10.1021/bi9604946 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV474 UT WOS:A1996UV47400008 PM 8679613 ER PT J AU Chuaqui, R Vargas, MP Castiglioni, T Elsner, B Zhuang, ZP EmmertBuck, M Merino, MJ AF Chuaqui, R Vargas, MP Castiglioni, T Elsner, B Zhuang, ZP EmmertBuck, M Merino, MJ TI Detection of heterozygosity loss in microdissected fine needle aspiration specimens of breast carcinoma SO ACTA CYTOLOGICA LA English DT Article DE breast neoplasms; aspiration biopsy; heterozygosity ID POLYMERASE CHAIN-REACTION; FLOW-CYTOMETRY; IN-SITU; CYTOLOGY; MANAGEMENT; LESIONS; POLYMORPHISM; DIAGNOSIS; BIOPSIES; CANCERS AB OBJECTIVE: To use the polymerase chain reaction (PCR) to detect loss of heterozygosity (LOH) in microdissected cells from cytologic smears obtained by fine needle aspiration (FNA) from 20 cases of invasive breast carcinoma. STUDY DESIGN: In each case, histologic sections of the primary tumor were also available. Tumor and nontumor cells were dissected from both the cytologic smear and tissue section in all cases except in three smears that showed only tumor cells. RESULTS: LOH was identified in 10 of 19 informative cases using two polymorphic DNA markers at chromosome 11q13 (INT-2, PYGM). The same results were obtained in both the cytologic and histologic specimens, including three cases that had hypocellular cytologic smears. CONCLUSION: FNA of breast lesions provides adequate samples for direct microdissection of the cytologic smear to defect LOH using PCR amplification. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. CTR MED EDUC & CLIN INVEST,DEPT PATHOL,BUENOS AIRES,DF,ARGENTINA. NR 34 TC 15 Z9 16 U1 0 U2 2 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD JUL-AUG PY 1996 VL 40 IS 4 BP 642 EP 648 PG 7 WC Pathology SC Pathology GA VQ191 UT WOS:A1996VQ19100004 PM 8693879 ER PT J AU Oliver, G Yannelli, J Solomon, D AF Oliver, G Yannelli, J Solomon, D TI Tumor-infiltrating lymphocytes - Cytologic, phenotypic and morphometric analysis SO ACTA CYTOLOGICA LA English DT Article DE tumor-infiltrating lymphocytes ID METASTATIC MELANOMA; IMMUNOTHERAPY AB OBJECTIVE: To characterize the cytologic, phenotypic and morphometric features of tumor-infiltrating lymphocytes (TILs). STUDY DESIGN: Morphology and cell size parameters of 50 TILs and five normal donor peripheral blood lymphocyte (PBL) specimens were compared using light microscopy, manual ocular measurements and digital image processing. RESULTS: Cytologically, all TILs demonstrated similar morphologic findings regardless of the initial tumor type. Changes included large, eccentric nuclei, sometimes hyperlobated; clumped chromatin; and prominent nucleoli. The cytoplasm was abundant and basophilic. Mitotic figures were usually evident. In addition, TIL showed significant increases in cell size parameters as compared to PBLs. CONCLUSION: The activated morphology of TILs resembles the appearance of high grade lymphoma. Several cell size parameters are increased; that may help to explain differences in previously reported trafficking patterns between TILs and peripheral blood lymphocytes. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NCI,CYTOPATHOL SECT,NIH,BETHESDA,MD 20892. NR 8 TC 3 Z9 3 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD JUL-AUG PY 1996 VL 40 IS 4 BP 691 EP 694 PG 4 WC Pathology SC Pathology GA VQ191 UT WOS:A1996VQ19100013 PM 8693888 ER PT J AU Zhang, ZX Anderson, DW Mantel, N Roman, GC AF Zhang, ZX Anderson, DW Mantel, N Roman, GC TI Motor neuron disease on Guam: Geographic and familial occurrence, 1956-85 SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE case registry epidemiology; incidence; motor neuron disease ID AMYOTROPHIC-LATERAL-SCLEROSIS; PARKINSONISM-DEMENTIA COMPLEX; CYCAD FLOUR; BMAA; EPIDEMIOLOGY; NEUROTOXINS; HYPOTHESIS; ETIOLOGY AB We investigated the geographic and familial occurrence of motor neuron disease (MND) on Guam, and then considered etiologic hypotheses related to cycad use and metal intoxication. The research was based on 303 Chamorros from Guam and 3 Chamorros from other Mariana Islands, all with MND onset on Guam during 1956-85. Inarajan and Umatac, two southern districts, each had, for both sexes combined, an average incidence rate significantly higher than the corresponding overall rate for Guam. Also, for each sex, geographic patterns of incidence were significantly related to 1) socioeconomic level (men only), 2) cycasin concentrations in cycad flour samples (men and women), 3) iron concentrations in water samples (men and women), 4) silicon concentrations in water samples (men only), and 5) cobalt and nickel concentrations in soil samples (men and women). The MND risk in susceptible sibships was about 7-28 times greater than that in the general population. The cycad hypothesis conforms somewhat better than the metal intoxication hypothesis with the data presented. C1 NINCDS,NIH,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. BEIJING UNION MED COLL HOSP,DEPT NEUROL,BEIJING,PEOPLES R CHINA. AMERICAN UNIV,DEPT MATH & STAT,WASHINGTON,DC 20016. NR 54 TC 36 Z9 37 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD JUL PY 1996 VL 94 IS 1 BP 51 EP 59 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA VE001 UT WOS:A1996VE00100009 PM 8874594 ER PT J AU Schindler, CW Goldberg, SR AF Schindler, CW Goldberg, SR TI Multiple systems approach to drug abuse: Implications for research and treatment SO ADDICTION LA English DT Editorial Material ID BEHAVIOR RP Schindler, CW (reprint author), NIDA,ADDICT RES CTR,DIR,PRECLIN PHARMACOL LAB,POB 5180,BALTIMORE,MD 21224, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JUL PY 1996 VL 91 IS 7 BP 957 EP 958 DI 10.1111/j.1360-0443.1996.tb03591.x PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA UW084 UT WOS:A1996UW08400007 ER PT J AU Launer, KJ Harris, T AF Launer, KJ Harris, T TI Weight, height and body mass index distributions in geographically and ethnically diverse samples of older persons SO AGE AND AGEING LA English DT Article DE anthropometry; elderly people; screening; epidemiology AB We compared anthropometric data (height, weight and body mass index) from 19 geographically and ethnically varied samples of community-dwelling elderly people. Participants were stratified into three age groups, 60-69, 70-79 and 80 years or older. We present-age-group-specific means and standard deviations for height, weight and body mass index (BMI, weight/height(2)) and the prevalence of underweight (BMI < 20) and overweight (BMI greater than or equal to 30). Across studies there are large differences in the prevalence of overweight and underweight, but in all studies mean height and BMI decreased with age. In general, mean BMI among 70-79-year-old women is greater than that for men of a similar age, and the Mediterranean samples are heavier for height than samples from Western Europe, Asia, Africa and the United States. The comparisons suggest that the sensitivity and specificity of a fixed cut-off for underweight and overweight are likely to differ by sex, age, and geographic location in samples of older persons. C1 NIA,EPIDEMIOL DEMOG & BIOSTAT PROGRAM,NIH,BETHESDA,MD. RP Launer, KJ (reprint author), NATL INST PUBL HLTH & ENVIRONM PROTECT,RIVM CCM,POB 1,NL-3720 BA BILTHOVEN,NETHERLANDS. NR 10 TC 32 Z9 32 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0002-0729 J9 AGE AGEING JI Age Ageing PD JUL PY 1996 VL 25 IS 4 BP 300 EP 306 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA UY163 UT WOS:A1996UY16300007 ER PT J AU Alexander, NJ Alexander, V Allen, S Dorflinger, L Dommel, WF Duerr, A Elias, C Feigal, D Gollub, E Gabelnick, H Harris, M Hitchcock, PJ Karam, M Kazempour, K Lange, J Roddy, R Rowe, P Rosenberg, Z Perriens, J Stone, A Stratton, P AF Alexander, NJ Alexander, V Allen, S Dorflinger, L Dommel, WF Duerr, A Elias, C Feigal, D Gollub, E Gabelnick, H Harris, M Hitchcock, PJ Karam, M Kazempour, K Lange, J Roddy, R Rowe, P Rosenberg, Z Perriens, J Stone, A Stratton, P TI Recommendations for the development of vaginal microbicides SO AIDS LA English DT Article DE HIV prevention; sexually transmitted disease prevention; vaginal microbicides ID NONOXYNOL-9; WOMEN; HIV AB Vaginal microbicides are products for vaginal administration that can be used to prevent HIV infection and other sexually transmitted diseases (STD). We recognize two potential sources of vaginal microbicides: existing spermicides and new products (new products may or may not be spermicidal). This document is meant to serve as a general guide for development and evaluation of existing and new products. For new products preclinical studies will be required. Depending upon indication, in vitro activity against HIV, target STD, and sperm should also be assessed. Compatibility with barrier method materials should also be evaluated. The physical-chemical properties of the active agent and the clinical formulation should be assessed. Animals studies should be conducted to assess its safety and predict dosing; use of various models to assess local toxicity is indicated and microbicidal activity of the product may be evaluated if appropriate models are available. Carcinogenicity testing and segment III reproduction studies (perinatal and post-natal studies in rats) may be performed concurrently with Phase III clinical trials. All vaginal microbicides, including existing spermicides and new products, should be clinically evaluated for safety and efficacy. Safety studies are necessary because irritation of vaginal and cervical mucosae has been recently associated with spermicide use and those lesions might increase HIV transmission. Efficacy studies to assess prevention of HIV infection and/or STD, depending upon the product indication, should then be conducted with products that have been evaluated for safety and appear to be non-toxic to tissue. For spermicidal microbicides contraceptive efficacy studies will be needed. C1 NICHHD,NIH,BETHESDA,MD 20892. COMMUNITY FAMILY PLANNING COUNCIL,NEW YORK,NY. ADV HLTH TECHNOL,WASHINGTON,DC. FAMILY HLTH INT,RES TRIANGLE PK,NC 27709. NIH,OFF PROTECT RES RISKS,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,DIV REPROD HLTH,ATLANTA,GA 30341. POPULAT COUNCIL,BANGKOK,THAILAND. US FDA,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. AIDS COORDINATING OFF,PHILADELPHIA,PA. CONRAD PROGRAM,ARLINGTON,VA. SOC WOMEN & AIDS AFRICA,FREETOWN,SIERRA LEONE. NIAID,NIH,BETHESDA,MD 20892. WHO,GLOBAL PROGRAMME AIDS,CH-1211 GENEVA,SWITZERLAND. WHO,SPECIAL PROGRAMME RES DEV & RES TRAINING HUMA,CH-1211 GENEVA,SWITZERLAND. MRC,LONDON W1N 4AL,ENGLAND. RP Alexander, NJ (reprint author), UNAIDS,INT WORKING GRP VAGINAL MICROBICIDES,20 AVE APPIA,CH-1211 GENEVA 27,SWITZERLAND. NR 16 TC 0 Z9 0 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUL PY 1996 VL 10 IS 8 BP 1 EP 6 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UW089 UT WOS:A1996UW08900026 ER PT J AU Brookmeyer, R Mehendale, SM Pelz, RK Shepherd, ME Quinn, T Rodrigues, JJ Bollinger, RC AF Brookmeyer, R Mehendale, SM Pelz, RK Shepherd, ME Quinn, T Rodrigues, JJ Bollinger, RC TI Estimating the rate of occurrence of new HIV infections using serial prevalence surveys: The epidemic in India SO AIDS LA English DT Letter C1 NATL AIDS RES INST,PUNE,MAHARASHTRA,INDIA. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,NIH,BETHESDA,MD 20892. RP Brookmeyer, R (reprint author), JOHNS HOPKINS UNIV,DEPT BIOSTAT,615 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 6 TC 16 Z9 16 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUL PY 1996 VL 10 IS 8 BP 924 EP 925 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UW089 UT WOS:A1996UW08900020 PM 8828754 ER PT J AU Miller, RH Turk, SR Black, RJ Bridges, S Sarver, N AF Miller, RH Turk, SR Black, RJ Bridges, S Sarver, N TI Conference summary: Novel HIV therapies - From discovery to clinical proof of concept SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material ID INVIVO C1 NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. NR 32 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL 1 PY 1996 VL 12 IS 10 BP 859 EP 865 DI 10.1089/aid.1996.12.859 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UU506 UT WOS:A1996UU50600003 PM 8798970 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series - John Paul Jones (1747-1792) - American Naval Officer SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article RP Cohen, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JUL-AUG PY 1996 VL 17 IS 4 BP 221 EP 223 DI 10.2500/108854196778996949 PG 3 WC Allergy SC Allergy GA VC299 UT WOS:A1996VC29900009 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series - William IV (1765-1835) - King of Great Britain, Ireland and Hanover SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article RP Cohen, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JUL-AUG PY 1996 VL 17 IS 4 BP 224 EP 225 PG 2 WC Allergy SC Allergy GA VC299 UT WOS:A1996VC29900010 PM 8871743 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series - Ludwig van Beethoven (1770-1827) - German composer SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article RP Cohen, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JUL-AUG PY 1996 VL 17 IS 4 BP 226 EP 228 PG 3 WC Allergy SC Allergy GA VC299 UT WOS:A1996VC29900011 PM 8871744 ER PT J AU Brand, FN Larson, M Friedman, LM Kannel, WB Castelli, WP AF Brand, FN Larson, M Friedman, LM Kannel, WB Castelli, WP TI Epidemiologic assessment of angina before and after myocardial infarction: The Framingham Study SO AMERICAN HEART JOURNAL LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; PECTORIS C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP Brand, FN (reprint author), BOSTON UNIV,SCH MED,FRAMINGHAM HEART STUDY,PREVENT MED & EPIDEMIOL SECT,5 THURBER ST,FRAMINGHAM,MA 01701, USA. FU NHLBI NIH HHS [NIH-NO1-HV-92922, NIH-NO1-HV-52971] NR 26 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 1996 VL 132 IS 1 BP 174 EP 178 DI 10.1016/S0002-8703(96)90406-8 PN 1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UW812 UT WOS:A1996UW81200024 PM 8701860 ER PT J AU Bennett, JS Feigley, CE Underhill, DW Drane, W Payne, TA Stewart, PA Herrick, RF Utterback, DF Hayes, RB AF Bennett, JS Feigley, CE Underhill, DW Drane, W Payne, TA Stewart, PA Herrick, RF Utterback, DF Hayes, RB TI Estimating the contribution of individual work tasks to room concentration: Method applied to embalming SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Article DE embalming; emission rates; exposure; formaldehyde; mathematical model; nonlinear regression AB A new approach for estimating emission rates from continuous concentration data was developed and applied to formaldehyde measurements collected during 25 embalmings. The instantaneous emission rate was estimated from the contaminant mass balance, which set the rate of emission equal to the sum of the rate of buildup in the room and the rate of removal in the exhaust flow. The generation rate of each specific work task was modeled using an equation that considered both the buildup and decay of the generation rare. Each term of the full modeling equation corresponded to a work task or vent that occurred during the embalmings. The expected formaldehyde contribution of individual work tasks or events was then estimated by integrating each term using the gamma function. The work tasks or events with the largest formaldehyde contributions were aspiration of viscera after treatment with cavity fluid, embalming fluid spill, application of osmotic gel, and trocar cavity infusion. This analysis showed the relative importance of individual work tasks or events as contributors to the workroom formaldehyde concentration. This reconstruction of emission rates from concentration data is a general approach that may be used to proceed more effectively with control efforts in other processes where continuous data are available from reasonably well-mixed rooms. C1 UNIV S CAROLINA,SCH PUBL HLTH,DEPT ENVIRONM HLTH SCI,COLUMBIA,SC 29208. UNIV S CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,COLUMBIA,SC 29208. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20882. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA 02115. NIOSH,DIV SURVEILLANCE HAZARD EVALUAT & FIELD STUDIES,CINCINNATI,OH 45226. NR 8 TC 11 Z9 11 U1 0 U2 2 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 SN 0002-8894 J9 AM IND HYG ASSOC J JI Am. Ind. Hyg. Assoc. J. PD JUL PY 1996 VL 57 IS 7 BP 599 EP 609 DI 10.1202/0002-8894(1996)057<0599:ETCOIW>2.0.CO;2 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA UW928 UT WOS:A1996UW92800002 ER PT J AU Dorgan, JF Reichman, ME Judd, JT Brown, C Longcope, C Schatzkin, A Forman, M Campbell, WS Franz, C Kahle, L Taylor, PR AF Dorgan, JF Reichman, ME Judd, JT Brown, C Longcope, C Schatzkin, A Forman, M Campbell, WS Franz, C Kahle, L Taylor, PR TI Relation of energy, fat, and fiber intakes to plasma concentrations of estrogens and androgens in premenopausal women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE diet; intake; dietary fats; dietary fiber; diet records; estrogens; androgens ID BREAST-CANCER RISK; HORMONE-BINDING GLOBULIN; PROTEIN-BOUND ESTRADIOL; MENSTRUAL-CYCLE; DIETARY-FAT; NUTRIENT INTAKE; FOOD-INTAKE; POSTMENOPAUSAL WOMEN; CIRCULATING LEVELS; ANIMAL PROTEIN AB To evaluate whether diet may influence the incidence of hormone-dependent cancers through an effect on blood estrogen and androgen concentrations, we analyzed diet-blood hormone relations in a cross-sectional study, Dietary energy, fat, and fiber intakes were estimated from 7-d food records completed by 90 premenopausal women on days 14-20 of their menstrual cycles. Fasting blood specimens were collected on days 5-7, 12-15, and 21-23 of each participant's cycle and pooled to create follicular-, midcycle-, and luteal-phase samples, respectively, for analysis. Energy intake was associated inversely with plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS), averaged across the three menstrual cycle phases, and directly with the probability of a luteal-phase rise in progesterone. For each additional 1 MJ (239 kcal) consumed, androstenedione decreased by 6.0% (95% CI: -8.4%, -3.6%), DHEAS decreased by 5.1% (95% CI: -9.6%, -0.4%), and the probability of a progesterone rise increased by 60% (95% CI: 5%, 145%). After energy intake was adjusted for, the ratio of polyunsaturated to saturated fat (P:S) in the diet was significantly inversely associated with plasma estradiol and estrone during the luteal phase of the menstrual cycle. For each 0.1 increment in the P:S, there was a 7.6% (95% CI: -14.3%, -0.5%) decrease in estradiol and a 6.8% (95% CI: -12.7%, -0.6%) decrease in estrone. Results of this cross-sectional study support a relation between both energy and fat ingestion and plasma sex hormone concentrations in premenopausal women. C1 USDA ARS,BELTSVILLE HUMAN NUTR RES CTR,DIET & HUMAN PERFORMANCE LAB,BELTSVILLE,MD. UNIV MASSACHUSETTS,SCH MED,DEPT OBSTET & GYNECOL,WORCESTER,MA 01605. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01605. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Dorgan, JF (reprint author), NCI,DCPC,CPSB,EXECUT PLAZA N,ROOM 211,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 72 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1996 VL 64 IS 1 BP 25 EP 31 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UT904 UT WOS:A1996UT90400005 PM 8669410 ER PT J AU Graubard, BI Korn, EL AF Graubard, BI Korn, EL TI Survey inference for subpopulations SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE epidemiologic methods; statistics AB One frequently analyzes a subset of the data collected in a survey when interest focuses on individuals in a certain subpopulation of the sampled population. Although it may seem natural to eliminate from the data set all data from individuals outside the subpopulation before analysis, this procedure may yield incorrect standard errors and confidence intervals. The authors give two examples of this using data from the 1987 National Health Interview Survey and the 1986 National Mortality Followback Survey. The correct method of analysis is described, as well as a simple condition that, when satisfied, ensures that the elimination approach yields identical answers to the correct method. C1 NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP Graubard, BI (reprint author), NCI,BIOMETRY BRANCH EPN344,BETHESDA,MD 20892, USA. NR 17 TC 35 Z9 35 U1 1 U2 3 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 1996 VL 144 IS 1 BP 102 EP 106 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UT906 UT WOS:A1996UT90600012 PM 8659480 ER PT J AU Nichols, RC Rudolphi, O Ek, B Exelbert, R Plotz, PH Raben, N AF Nichols, RC Rudolphi, O Ek, B Exelbert, R Plotz, PH Raben, N TI Glycogenosis type VII (Tarui disease) in a Swedish family: Two novel mutations in muscle phosphofructokinase gene (PFK-M) resulting in intron retentions SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ASHKENAZI-JEWISH PATIENTS; DEFICIENCY; EXPRESSION; ASSIGNMENT; CLONING; REGION; SPLICE; CDNA AB Phosphofructokinase (PFK) plays a major role in glycolysis. Human PFK is composed of three isoenzyme subunits (muscle [M], liver [L], and platelet [P]), which are encoded by different genes. Deficiency of muscle isoenzyme (PFK-M), glycogenosis type VII (Tarui disease), is an autosomal recessive disorder characterized by an exertional myopathy and hemolytic syndrome. Several disease-causing mutations have been identified in the PFK-M gene in Japanese, Ashkenazi Jewish, Italian, French Canadian, and Swiss patients. We describe the genetic defect in a Swedish family with affected individuals in two generations. The patients are compound heterozygotes: two different mutations result in retention of intron 13 or intron 16 sequences into mRNA. A G1127A transition destroys the 5' donor site of intron 13, resulting in a 155-nt retention of the intronic sequence. An a-to-g base change in intron 16 creates a new acceptor splice site, resulting in a 63-nt retention of intronic sequence. Both mutations are predicted to result in premature termination of translation. Some of the transcripts generated from, the intron 16 mutated allele also contain intron 10 sequence unspliced. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. UMEA UNIV,DEPT CLIN CHEM,S-90187 UMEA,SWEDEN. UMEA UNIV,DEPT INTERNAL MED,S-90187 UMEA,SWEDEN. NR 34 TC 16 Z9 16 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1996 VL 59 IS 1 BP 59 EP 65 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA VL455 UT WOS:A1996VL45500010 PM 8659544 ER PT J AU Nobukuni, Y Watanabe, A Takeda, K Skarka, H Tachibana, M AF Nobukuni, Y Watanabe, A Takeda, K Skarka, H Tachibana, M TI Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HELIX-LOOP-HELIX; HUMAN TYROSINASE GENE; TRANSCRIPTION FACTOR; MICROPHTHALMIA GENE; MOLECULAR-BASIS; PAIRED DOMAIN; HUMAN HOMOLOG; DNA-BINDING; MOUSE; EXPRESSION AB Waardenburg syndrome type 2 (WS2) is a dominantly inherited disorder characterized by a pigmentation anomaly and hearing impairment due to lack of melanocyte. Previous work has linked a subset of families with WS2 (WS2A) to the MITF gene that encodes a transcription factor with a basic-helix-loop-helix-leucine zipper (bHLH-Zip) motif and that is involved in melanocyte differentiation. Several splice-site and missense mutations have been reported in individuals affected with WS2A. In this report, we have identified two novel point mutations in the MITF gene in affected individuals from two different families with WS2A. The two mutations (C760-->T and C895-->T) create stop codons in exons 7 and 8, respectively. Corresponding mutant alleles predict the truncated proteins lacking HLH-Zip or Zip structure. To understand how these mutations cause WS2 in heterozygotes, we generated mutant MITF cDNAs and used them for DNA-binding and luciferase reporter assays. The mutated MITF proteins lose the DNA-binding activity and fail to trans-activate the promoter of tyrosinase, a melanocyte-specific enzyme. However, these mutated proteins do not appear to inter fere with the activity of wild-type MITF protein in these assays, indicating that they do not show a dominant-negative effect. These findings suggest that the pheno types of the two families with WS2A in the present study are caused by loss-of-function mutations in one of the two alleles of the MITF gene, resulting in haploinsufficiency of the MITF protein, the protein necessary for normal development of melanocytes. C1 NIDCD,MOL GENET LAB,NIH,ROCKVILLE,MD 20850. NIMH,CLIN NEUROGENET BRANCH,NIH,BETHESDA,MD 20892. NR 37 TC 73 Z9 81 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1996 VL 59 IS 1 BP 76 EP 83 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA VL455 UT WOS:A1996VL45500012 PM 8659547 ER PT J AU Guldberg, P Levy, HL Hanley, WB Koch, R Matalon, R Rouse, BM Trefz, F delaCruz, F Henriksen, KF Guttler, F AF Guldberg, P Levy, HL Hanley, WB Koch, R Matalon, R Rouse, BM Trefz, F delaCruz, F Henriksen, KF Guttler, F TI Phenylalanine hydroxylase gene mutations in the United States: Report from the maternal PKU collaborative study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RNA SPLICE JUNCTIONS; MOLECULAR ANALYSIS; SOUTHERN EUROPE; MESSENGER-RNA; PHENYLKETONURIA; DNA; SPECTRUM; SEQUENCE; REGIONS; ALLELES AB The major cause of hyperphenylalaninemia is mutations in the gene encoding phenylalanine hydroxylase (PAH). The lino,vn mutations have been identified primarily in European patients. The purpose of this study was to determine the spectrum of mutations responsible for PAH deficiency in the United States. One hundred forty-nine patients enrolled in the Maternal PKU Collaborative Study were subjects for clinical and molecular investigations. PAH gene mutations associated with phenylketonuria (PKU) or mild hyperphenylalaninemia (MHP) were identified on 279 of 294 independent mutant chromosomes, a diagnostic efficiency of 95%. The spectrum is composed of 71 different mutations, including 47 missense mutations, 11 splice mutations, 5 nonsense mutations, and 8 microdeletions. Sixteen previously unreported mutations were identified. Among the novel mutations, five were found in patients with MHP, and the remainder were found in patients with PKU. The most common mutations were R408W, IVS12nt1g-->a, and Y414C, accounting for 18.7%, 7.8%, and 5.4% of the mutant chromosomes, respectively. Thirteen mutations had relative frequencies of 1%-5%, and 55 mutations each had frequencies less than or equal to 1%. The mutational spectrum corresponded to that observed for the European ancestry of the U.S. population. To evaluate the extent of allelic variation at the PAH locus within the United States in comparison with other populations, we used allele frequencies to calculate the homozygosity for 11 populations where >90% ascertainment of mutations has been obtained. The United States was shown to contain one of the most heterogeneous populations, with homozygosity values similar to Sicily and ethnically mixed sample populations in Europe. The extent of allelic heterogeneity must be a major determining factor in the choice of mutation-detection methodology for molecular diagnosis in PAH deficiency. C1 NICHHD,BETHESDA,MD 20892. JOHN F KENNEDY INST,DANISH CTR HUMAN GENOME RES,DK-2600 GLOSTRUP,DENMARK. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. UNIV SO CALIF,LOS ANGELES,CA 90089. CHILDRENS HOSP,DIV MED GENET,LOS ANGELES,CA 90027. UNIV TEXAS,MED BRANCH,CHILDRENS HOSP,GALVESTON,TX 77550. CHILDRENS HOSP,RES INST,MIAMI,FL. UNIV TUBINGEN,REUTLINGEN,GERMANY. FU NICHD NIH HHS [N01-HD-Z-3155] NR 47 TC 58 Z9 64 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1996 VL 59 IS 1 BP 84 EP 94 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA VL455 UT WOS:A1996VL45500013 PM 8659548 ER PT J AU Chen, CJ Yu, MW Liaw, YF Wang, LW Chiamprasert, S Matin, F Hirvonen, A Bell, DA Santella, RM AF Chen, CJ Yu, MW Liaw, YF Wang, LW Chiamprasert, S Matin, F Hirvonen, A Bell, DA Santella, RM TI Chronic hepatitis B carriers with null genotypes of glutathione S-transferase M1 and T1 polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carcinoma SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID C VIRUS-ANTIBODIES; HUMAN LIVER CANCER; DIETARY AFLATOXINS; ALBUMIN ADDUCTS; DNA ADDUCTS; ASSOCIATION; INFECTION; TAIWAN; RATS; SUSCEPTIBILITY AB This study was carried out to elucidate the effect of glutathione S-transferase (GST) M1 and T1 polymorphisms on the aflatoxin-related hepatocarcinogenesis among chronic carriers of hepatitis B surface antigen (HBsAg). A total of 32 newly diagnosed hepatocellular carcinoma (HCC) cases and 73 age-matched controls selected from a cohort of 4,841 chronic HBsAg carriers who had been followed for 5 years were studied. The level of aflatoxin B-1 (AFB(1))-albumin adducts in their serum samples collected at the recruitment was examined by competitive enzyme-linked immunosorbance assay, and genotypes of GST hll and T1 were determined by PCR. There was a dose-response relationship between serum level of AFB(1)-albumin adducts and risk of HCC. The biological gradients between serum AFB(1)-albumin adducts level and HCC risk were observed among chronic HBsAg carriers who had null genotypes of GST M1 and/or T1 but not among those who had non-null genotypes. The multivariate-adjusted odds ratios of developing HCC for those who had low and high serum levels of AFB(1)-albumin adducts compared with those who had a undetectable adduct level as the referent (odds ratio = 1.0) were 4.1 and 12.4, respectively, for HBsAg carriers with null GST M1 genotype (P < .01, on the basis of the significance test for trend); 0.7 and 1.4 for those with nonnull CST M1 genotype (P = .98); 1.8 and 10.2 for those with null GST T1 genotype (P < .05); and 1.3 and 0.8 for those with non-null GST T1 genotype (P = .93). The interaction between serum AFB(1)-albumin adduct level and polymorphisms of GST M1 and T1 was at marginal statistical significance levels (.05 < P < .10). C1 CHANG GUNG MEM HOSP, LIVER UNIT, TAIPEI 10591, TAIWAN. COLUMBIA UNIV, SCH PUBL HLTH, DIV ENVIRONM HLTH SCI, NEW YORK, NY 10027 USA. NIEHS, BIOCHEM RISK ANAL LAB, RES TRIANGLE PK, NC 27709 USA. RP Chen, CJ (reprint author), NATL TAIWAN UNIV, COLL PUBL HLTH, INST EPIDEMIOL, 1 JEN AI RD SECT 1, TAIPEI 10018, TAIWAN. RI Chen, Chien-Jen/C-6976-2008; Liaw, Yun-Fan /B-4305-2009; OI Yu, Ming-Whei/0000-0002-8371-6236 FU NIEHS NIH HHS [ES05116, R01 ES005116] NR 41 TC 98 Z9 99 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1996 VL 59 IS 1 BP 128 EP 134 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA VL455 UT WOS:A1996VL45500018 PM 8659516 ER PT J AU Zheng, CJ Byers, B AF Zheng, CJ Byers, B TI When does maternal age-dependent trisomy 21 arise relative to meiosis? SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID MITOTIC ERRORS; NONDISJUNCTION; MECHANISM C1 UNIV WASHINGTON,DEPT GENET,SEATTLE,WA 98195. RP Zheng, CJ (reprint author), NIDCD,EPIDEMIOL STAT & DATA SYST BRANCH,NIH,EPS BLDG 432,6120 EXECUT BLVD,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM18541] NR 5 TC 5 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1996 VL 59 IS 1 BP 268 EP 269 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA VL455 UT WOS:A1996VL45500039 PM 8659537 ER PT J AU Xu, ZY Pan, GW Liu, LM Brown, LM Guan, DX Xiu, Q Sheng, JH Stone, BJ Dosemeci, M Fraumeni, JF Blot, WJ AF Xu, ZY Pan, GW Liu, LM Brown, LM Guan, DX Xiu, Q Sheng, JH Stone, BJ Dosemeci, M Fraumeni, JF Blot, WJ TI Cancer risks among iron and steel workers in Anshan, China .1. Proportional mortality ratio analysis SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE accidents; asbestos; colorectal neoplasm; esophagus neoplasm; foundry workers; lung neoplasm; polycyclic aromatic hydrocarbons; respiratory disease; silica; stomach neoplasm ID LUNG-CANCER; STOMACH; COLON; DUST; DIET AB A standardized proportional mortality ratio (SPMR) study of 8,887 deaths during 1980-1989 among male workers in a large integrated iron-steel complex in Anshan, China, was conducted to provide clues to occupational risk factors. Accidents and cancer accounted for a higher proportion of deaths among the iron-steel workers than among the general male population (SPMR = 1.21; 95% CI = 1.12-1.31 and 1.14; 95% CI = 1.10-1.18, respectively). Among all workers, SPMRs were significantly elevated for stomach, lung, and colorectal cancers (SPMR = 1.37, 1.37, 1.38, respectively), but not other cancers. Risks of stomach cancer appeared to be highest among workers employed in jobs with exposure to iron and coal dust, whereas significant increases in colorectal cancer were seen for loading and other dusty jobs and for administrative and sedentary jobs without dust exposure. Risks of lung cancer appeared increased for a variety of jobs throughout the complex, especially those with probable high levels of exposure to polycyclic hydrocarbons and asbestos. Risk of esophageal cancer was significantly elevated for fire-resistant brick makers, and risk of nonmalignant respiratory disease was significantly elevated for those employed as furnace workers, foundry workers, and fire-resistant brick makers. (C) 1996 Wiley-Liss, Inc. C1 NCI,DIV CANC EPIDEMIOL & GENET,NIH,BETHESDA,MD 20892. LIAONING PUBL HLTH & ANTIEPIDEM STN,SHENYANG,PEOPLES R CHINA. ANSHAN IRON STEEL COMPLEX,PUBL HLTH & ANTIEPIDEM STN,ANSHAN,PEOPLES R CHINA. NR 20 TC 28 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 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 1996 VL 30 IS 1 BP 1 EP 6 DI 10.1002/(SICI)1097-0274(199607)30:1<1::AID-AJIM1>3.0.CO;2-5 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UZ296 UT WOS:A1996UZ29600001 PM 8837675 ER PT J AU Xu, ZY Brown, LM Pan, GW Liu, TF Gao, GS Stone, BJ Cao, RM Guan, DX Sheng, JH Yan, ZS Dosemeci, M Fraumeni, JF Blot, WJ AF Xu, ZY Brown, LM Pan, GW Liu, TF Gao, GS Stone, BJ Cao, RM Guan, DX Sheng, JH Yan, ZS Dosemeci, M Fraumeni, JF Blot, WJ TI Cancer risks among iron and steel workers in Anshan, China .2. Case-control studies of lung and stomach cancer SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE asbestos; benzo(a)pyrene; coke oven workers; foundry workers; metal dust; polynuclear aromatic hydrocarbons; silica; lung neoplasm; stomach neoplasm; interview; questionnaire ID FOUNDRY WORKERS; POTTERY WORKERS; MORTALITY; EXPOSURE; COHORT; MINE; DUST; SILICA AB Nested case-control interview studies of lung cancer (610 incident cases), stomach cancer (292 incident cases), and 959 controls were conducted to follow up leads from a proportional mortality analysis of deaths among male workers in a large integrated iron-steel complex in Anshan, China. For lung cancer, after adjusting for the significant non-occupational risk factors (smoking, other pulmonary disease, family history of lung cancer, and low consumption of fruit or tea), risks were significantly elevated for those employed for 15 or move years in smelting and rolling (OR = 1.5, CI = 1.1-2.2), in the fire-resistant brick factory (OR = 2.9, CI = 1.4-5.9), in general loading (OR = 2.5, CI = 1.0-6.1), and as coke overt workers (OR = 3.4; CI = 1.4-8.5). For stomach cancer, after adjusting for consumption of pickled vegetables, prior gastric diseases, family history of stomach cancer, low intake of fruits and vegetables, and education, risks were significantly elevated for those employed for 15 or more years in ore sintering and transportation (OR = 2.1, CI = 1.0-4.4), in the fire-resistant brick factory (OR = 2.5, CI = 1.1-5.8), in general loading (OR = 3.2, CI = 1.2-8.9), as boilerworkers and cooks (OR = 2.6, CI = 1.2-5.6), and as coke oven workers (OR = 5.4, CI = 1.8-16.0). For both lung and stomach cancers, significant dose-response gradients were observed for exposure to total dust and benzo(a)pyrene, but not for specific chemical components of dust. Overall, long-term steel workers with exposure to workplace pollutants had a 40% increased risk of both lung and stomach cancers. These case-control studies confirm many of the occupational findings reported in the proportionate mortality analysis, and suggest avenues for further work to evaluate the carcinogenicity of individual components of dust. (C) 1996 Wiley-Liss, Inc. C1 NCI,DIV CANC EPIDEMIOL & GENET,NIH,BETHESDA,MD 20892. LIAONING PUBL HLTH & ANTIEPIDEM STN,SHENYANG,PEOPLES R CHINA. ANSHAN IRON STEEL COMPLEX,PUBL HLTH & ANTIEPIDEM STN,ANSHAN,PEOPLES R CHINA. LABOR HYG RES INST ANSHAN IRON STEEL COMPLEX,ANSHAN,PEOPLES R CHINA. NR 32 TC 58 Z9 65 U1 1 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 1996 VL 30 IS 1 BP 7 EP 15 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UZ296 UT WOS:A1996UZ29600002 PM 8837676 ER PT J AU Chow, WH Ji, BT Dosemeci, M McLaughlin, JK Gao, YT Fraumeni, JF AF Chow, WH Ji, BT Dosemeci, M McLaughlin, JK Gao, YT Fraumeni, JF TI Biliary tract cancers among textile and other workers in Shanghai, China SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE biliary tract cancers; textile work; occupational risks; registry-linkage study; China ID RISK-FACTORS; GALLBLADDER CANCER; OCCUPATIONAL EXPOSURE; ESOPHAGEAL CANCER; MORTALITY; GALLSTONES; INDUSTRY; PLANT AB Using occupational data for more than 500 patients with cancers of the biliary tract (CBT) diagnosed between 1980 and 1984 in Shanghai, and employment information from the 1982 census for the Shanghai population, the associations between CBT and occupational categories were examined by standardized incidence ratios (SIR). Compared to the general population, risk was elevated by nearly 40% among textile workers (SIR for women = 137, 95% CI = 106-175 and SIR for men = 137, 95% CI = 76-217), consistent with other investigations linking CBT to textile work. Increased risk were observed also among waiters/waitresses, male sanitation personnel and chemical workers, and female janitor and similar workers. Although causal inferences cannot be firmly drawn, our findings add to the limited evidence linking CBT to occupational exposures, especially in the textile industry. (C) 1996 Wiley-Liss, Inc. C1 NCI,DIV CANC EPIDEMIOL & GENET,ROCKVILLE,MD 20852. SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. COLUMBIA UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,NEW YORK,NY. NR 28 TC 5 Z9 5 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 1996 VL 30 IS 1 BP 36 EP 40 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UZ296 UT WOS:A1996UZ29600006 PM 8837680 ER PT J AU Infante, PF Schuman, LD Huff, J AF Infante, PF Schuman, LD Huff, J TI Fibrous glass insulation and cancer: Response and rebuttal SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE fibrous glass; mineral fibers; epidemiology; lung cancer; experimental data; causation ID FIBERGLASS MANUFACTURING FACILITY; MAN-MADE FIBERS; FOLLOW-UP; HISTORICAL COHORT; WORKERS; MORTALITY; INHALATION; TOXICITY; SMOKING AB In response to our commentary on fibrous glass and cancer [Infante et al., 1994], three letters have been received by the journal. The arguments put forth in these fetters do not lead us to alter our scientific view that fibrous glass insulation is carcinogenic. No information is given in the letters that has not previously been stated. Even though these letters raise the same diaphanous arguments, we believe that to preserve occupational and public health we must respond in detail to ensure that the contentions of the fibrous glass industry do not gain further acceptance. Thus, we respond to each letter in turn: The first by Weiss questions and distorts epidemiologic findings, the second by McConnell attempts to recant his past views on the carcinogenicity of fibrous glass and on the value of rodent bioassays in general, and the third by Hesterberg and Chase impugns our analyses demonstrating a positive cancer response in. their study. Lastly, we have not debated every issue raised in these letters because of space limitations, and have centered our responses on what we consider the major incongruities and falsities in each letter. Likewise, we have been selective in citing only relevant literature, or those reports used by the industry or its consultants to support their views. (C) 1996 Wiley-Liss, Inc. C1 NIEHS, ENVIRONM CARCINOGENESIS PROGRAM, NIH, RES TRIANGLE PK, NC 27709 USA. RP Infante, PF (reprint author), US DEPT LABOR, OCCUPAT SAFETY & HLTH ADMIN, HLTH STAND PROGRAMS, WASHINGTON, DC 20210 USA. NR 36 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 1996 VL 30 IS 1 BP 113 EP 120 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UZ296 UT WOS:A1996UZ29600021 PM 16374937 ER PT J AU Mojcik, CF Klippel, JH AF Mojcik, CF Klippel, JH TI End-stage renal disease and systemic lupus erythematosus SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID SINGLE-CENTER EXPERIENCE; CLINICAL COURSE; KIDNEY-TRANSPLANTATION; PERITONEAL-DIALYSIS; FOLLOW-UP; NEPHRITIS; RECURRENCE; HEMODIALYSIS; FAILURE; GLOMERULONEPHRITIS AB OBJECTIVE: To provide an overview of the course of systemic lupus erythematosus (SLE) following the onset of end-stage lupus nephropathy, regarding clinical and serological manifestations, survival on dialysis, and renal transplant outcomes. METHODS: A review of the pertinent literature, identified by a comprehensive Grateful Med search, was performed. RESULTS: There is a tendency for decreased clinical and serological lupus activity following the onset of end-stage renal disease. The pathophysiology of this quiescence remains unclear. Survival of lupus patients on dialysis is no different from that of non-SLE dialysis patients, and is better than that of several other rheumatic diseases. Following renal transplantation, there is no difference in patient or graft survival in lupus versus nonlupus patients. Like their nonlupus counterparts, SLE transplant patients do better with living relative grafts and/or regimens containing cyclosporin A. Transplantation is not recommended within 3 months of the initiation of dialysis to allow possible recovery from the acute renal failure. Transplantation during an acute exacerbation of SLE is controversial, and may increase the risk of poor outcomes. Recurrence of lupus in transplanted allografts, often with the same histopathology as in the native kidney, occurs at a rate (2.7% to 3.8%) comparable to that for all allograft transplant failures (2% to 4%). CONCLUSIONS: End-stage lupus nephropathy patients require less medication owing to decreased disease activity. They are good candidates for dialysis and renal transplantation, with survival and recurrence rates no different from those of other patients with end-stage renal disease. C1 NIAMSD,NIH,BETHESDA,MD 20892. NIAID,NIH,BETHESDA,MD 20892. NR 59 TC 91 Z9 97 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 1996 VL 101 IS 1 BP 100 EP 107 DI 10.1016/S0002-9343(96)00074-5 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA UY647 UT WOS:A1996UY64700015 PM 8686702 ER PT J AU Colborn, AP AF Colborn, AP TI A case for case study research SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Editorial Material C1 NATL INST HLTH,DEPT REHABIL MED,OCCUPAT THERAPY SECT,BETHESDA,MD. NR 7 TC 1 Z9 1 U1 0 U2 2 PU AMER OCCUPATION THERAPY ASSN PI ROCKVILLE PA 1383 PICCARD DRIVE PO BOX ROCKVILLE, MD 20850-4375 SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD JUL-AUG PY 1996 VL 50 IS 7 BP 592 EP 594 PG 3 WC Rehabilitation SC Rehabilitation GA UY446 UT WOS:A1996UY44600015 PM 8819613 ER PT J AU Han, DP Wisniewski, SR Wilson, LA Barza, M Vine, AK Doft, BH Kelsey, SF Blodi, BA Elner, SG Johnson, MW Jessup, LM Khanderia, S Pierson, CL Willis, J McIver, F Stanley, S Sneed, SR Capone, A Aaberg, TM Lim, JI Sternberg, P Coffman, DS Moore, CN Gardner, SK Nolte, FS Fremstad, A Gibbs, D Gilman, J Swords, R Aguilar, HE Meredith, TA Lakhanpal, V Christian, FD Hood, MA Schwalbe, RS Billings, EE Buie, W Mallonee, JJ Millar, MA Verbeek, S Campochiaro, PA Palardy, CB Reynolds, L Dick, JD Cain, D DAmico, DJ Frederick, AR Morley, MG Pesavento, RD Puliafito, CA Topping, TM Finn, SM Raymond, LA Baker, AS Paton, B Evans, C Napoli, J Kiernan, C Makris, K McInnes, T Reidy, WT White, R Garfinkel, RA Pilkerton, AR Frantz, RA Abernathy, GB Barbaccia, JG Ensey, HR Ormes, CA Park, CH Caplan, J Russell, K Toma, R Packo, KH deBustros, S Flood, TP Glazer, L DeAlba, M Evanich, E Montwill, MA Rothman, JJ Ruderman, G Beard, M William, SM AF Han, DP Wisniewski, SR Wilson, LA Barza, M Vine, AK Doft, BH Kelsey, SF Blodi, BA Elner, SG Johnson, MW Jessup, LM Khanderia, S Pierson, CL Willis, J McIver, F Stanley, S Sneed, SR Capone, A Aaberg, TM Lim, JI Sternberg, P Coffman, DS Moore, CN Gardner, SK Nolte, FS Fremstad, A Gibbs, D Gilman, J Swords, R Aguilar, HE Meredith, TA Lakhanpal, V Christian, FD Hood, MA Schwalbe, RS Billings, EE Buie, W Mallonee, JJ Millar, MA Verbeek, S Campochiaro, PA Palardy, CB Reynolds, L Dick, JD Cain, D DAmico, DJ Frederick, AR Morley, MG Pesavento, RD Puliafito, CA Topping, TM Finn, SM Raymond, LA Baker, AS Paton, B Evans, C Napoli, J Kiernan, C Makris, K McInnes, T Reidy, WT White, R Garfinkel, RA Pilkerton, AR Frantz, RA Abernathy, GB Barbaccia, JG Ensey, HR Ormes, CA Park, CH Caplan, J Russell, K Toma, R Packo, KH deBustros, S Flood, TP Glazer, L DeAlba, M Evanich, E Montwill, MA Rothman, JJ Ruderman, G Beard, M William, SM TI Spectrum and susceptibilities of microbiologic isolates in the endophthalmitis vitrectomy study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID STAPHYLOCOCCUS-EPIDERMIDIS ENDOPHTHALMITIS; EXTRACAPSULAR CATARACT-EXTRACTION; ACUTE POSTOPERATIVE ENDOPHTHALMITIS; INTRAOCULAR-LENS IMPLANTATION; INFECTIOUS ENDOPHTHALMITIS; METHICILLIN-RESISTANT; PSEUDOPHAKIC ENDOPHTHALMITIS; INTRAVITREOUS CEFTAZIDIME; BACTERIAL-CONTAMINATION; AMINOGLYCOSIDE TOXICITY AB PURPOSE: To determine the microbiologic spectrum and antibiotic susceptibilities of infecting organisms in postoperative endophthalmitis and to evaluate the effects of operative factors on the microbiologic spectrum. METHODS: Patients with bacterial endophthalmitis presenting within six weeks of cataract extraction or secondary intraocular lens implantation (IOL) were evaluated. Cultures and Gram stains were performed on intraocular specimens and susceptibility tests on the isolates. RESULTS: Confirmed microbiologic growth was demonstrated from intraocular specimens from 291 of 420 patients (69.3%), Gram-positive bacteria were isolated from 274 patients (94.2%) with confirmed growth and gram-negative bacteria from 19 (6.5%). Two hundred twenty-six of the 323 isolates obtained (70.0%) were gram-positive, coagulase negative micrococci, 32 (9.9%) Staphylococcus aureus, 29 (9.0%) Streptococcus species, seven (2.2%) Enterococcus species, ten (3.1%) miscellaneous gram-positive species, and 19 (5.9%) gram-negative species, All gram-positive isolates tested were susceptible to vancomycin, Seventeen gram-negative isolates (89%) were susceptible to both amikacin and ceftazidime and two (11%) were resistant to both. Anterior chamber or secondary IOL implantations were associated with higher rates of infection with gram-positives other than coagulase-negative micrococci than were posterior chamber IOL implantations (P = .022) or primary cataract extractions (P = .024). CONCLUSIONS: Gram-positive, coagulase-negative micrococci predominated in this series, Vancomycin was active against all gram-positive isolates tested, Amikacin and ceftazidime showed equivalent activity against gram-negative isolates, Secondary or anterior chamber lens implantations were associated with a possible spectrum shift toward gram-positive organisms other than the coagulase-negative micrococci. C1 MED COLL WISCONSIN,DEPT OPHTHALMOL,MILWAUKEE,WI 53226. EMORY EYE CTR,ATLANTA,GA. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. UNIV MICHIGAN,WK KELLOGG EYE CTR,ANN ARBOR,MI 48105. RETINAL VITREOUS CONSULTANTS,PITTSBURGH,PA. UNIV MARYLAND EYE ASSOCIATES,BALTIMORE,MD. JOHNS HOPKINS UNIV,BALTIMORE,MD. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RETINA GRP WASHINGTON,CHEVY CHASE,MD. RUSH UNIV,INGALLS HOSP,CHICAGO,IL 60612. RETINA ASSOCIATES CLEVELAND INC,CLEVELAND,OH. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV MINNESOTA,EDINA,MN. RETINA VITREOUS CTR PA,EDISON,NJ. UNIV FLORIDA,GAINESVILLE,FL. PENN STATE UNIV,HERSHEY,PA. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV SO CALIF,LOS ANGELES,CA. UNIV LOUISVILLE,KENTUCKY LIONS EYE RES INST,LOUISVILLE,KY 40292. UNIV S FLORIDA,N TAMPA,FL. DEAN A MCGEE EYE INST,OKLAHOMA CITY,OK. THOMAS JEFFERSON UNIV,WILLS EYE HOSP,PHILADELPHIA,PA 19107. ASSOCIATED RETINAL CONSULTANTS PC,ROYAL OAK,MI. RETINA CONSULTANTS,SAN DIEGO,CA. UNIV S FLORIDA,S TAMPA,FL. RETINA CONSULTANTS ASSOCIATES INC,TOLEDO,OH. GEORGETOWN UNIV,WASHINGTON,DC. UNIV WISCONSIN,MADISON,WI. NEI,PROGRAM OFF,BETHESDA,MD. RP Han, DP (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,ENDOPHTHALMITIS VIRECTOMY STUDY COORDINATING CTR,PITTSBURGH,PA 15261, USA. OI Wisniewski, Stephen/0000-0002-3877-9860 FU NEI NIH HHS [EY08150, EY08151, EY08210] NR 56 TC 350 Z9 369 U1 1 U2 17 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 1996 VL 122 IS 1 BP 1 EP 17 PG 17 WC Ophthalmology SC Ophthalmology GA UX374 UT WOS:A1996UX37400001 PM 8659579 ER PT J AU Keleti, J Quezado, MM Abaza, MM Raffeld, M Tsokos, M AF Keleti, J Quezado, MM Abaza, MM Raffeld, M Tsokos, M TI The MDM2 oncoprotein is overexpressed in rhabdomyosarcoma cell lines and stabilizes wild-type p53 protein SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; TRANSFORMED-CELLS; HUMAN SARCOMAS; MUTATIONS; AMPLIFICATION; ANTIGEN; ONCOGENE; TRANSACTIVATION; EXPRESSION; IDENTIFICATION AB MDM2 gene overexpression has been implicated in the pathogenesis of human neoplasia via inhibition of the p53 tumor-suppressor function. To investigate the potential involvement of the MDM2 oncogene in the pathogenesis of childhood rhabdomyosarcoma (RMS), we studied MDM2 abnormalities in six RMS cell lines in correlation with the p53 status. Three showed overexpression of MDM2 mRNA and protein, one with concomitant MDM2 mRNA and protein, one with concomitant MDM2 gene amplification. All three lacked p53 mutation and expressed low levels of p53 mRNA but exhibited elevated p53 proteins. Double immunostaining revealed that the overexpressed MDM2 and p53 proteins were co-localized to the same cell nuclei. Furthermore, the two proteins were physically associated, as shown by co-immunoprecipitation and Western blot analysis. The half-life of the p53 protein was prolonged in the MDM2-overexpressing RMS cells. The extended half-life of the wild-type p53 protein and its complex formation with the elevated MDM2 suggest that the underlying mechanism for p53 protein accumulation in these cell lines is p53 stabilization by an overabundant MDM2 protein. The overexpressed MDM2 protein had a short half-life. The three remaining RMS cell lines exhibited low MDM2 mRNA and protein levels and carried p53 mutations. This study suggests that MDM2 overexpression represents an alternative mechanisms for p53 inactivation in a subset of childhood RMS without p53 mutations. The results further indicate that the elevated MDM2 protein is responsible for wild-type p53 protein accumulation via stabilization. C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,PEDIAT TUMOR BIOL ULTRASTRUCT PATHOL SECT,NIH,BETHESDA,MD 20892. NR 58 TC 71 Z9 72 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1996 VL 149 IS 1 BP 143 EP 151 PG 9 WC Pathology SC Pathology GA UV051 UT WOS:A1996UV05100018 PM 8686737 ER PT J AU Sherer, DM AF Sherer, DM TI Spontaneous torticollis in a breech-presenting fetus delivered by an atraumatic elective cesarean section: A case and review of the literature SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Review DE breech presentation; ultrasonography; oligohydramnios; torticollis; birth trauma ID CONGENITAL MUSCULAR TORTICOLLIS; TERM FOLLOW-UP; INFANTS AB A non-laboring patient with a breech-presenting fetus and oligohydramnios at 41 weeks' gestation underwent elective cesarean delivery. The infant was delivered atraumatically through a wide transverse incision of the lower uterine segment. Severe left-sided torticollis was noted immediately at delivery. The torticollis subsequently responded to physiotherapy with minimal residual facial asymmetry. This case and the literature suggest that torticollis itself may predispose to breech presentation Alternatively, in the case presented, oligohydramnios with subsequent; restricted posture may have contributed to the underlying pathophysiology of this phenomena, which previously has been noted as associated with and as a possible sequela of traumatic vaginal breech delivery. C1 GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,NICHD,PERINATL RES FACIL,WASHINGTON,DC 20057. NR 17 TC 5 Z9 5 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD JUL PY 1996 VL 13 IS 5 BP 305 EP 307 DI 10.1055/s-2007-994347 PG 3 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA VC691 UT WOS:A1996VC69100009 PM 8863951 ER PT J AU Kremer, R Woodworth, CD Goltzman, D AF Kremer, R Woodworth, CD Goltzman, D TI Expression and action of parathyroid hormone-related peptide in human cervical epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE calcium; retinoic acid; human papilloma virus ID SERUM-FREE MEDIUM; PAPILLOMAVIRUS TYPE-16; GENE-EXPRESSION; HUMAN KERATINOCYTES; GROWTH-FACTORS; MESSENGER-RNA; PROTEIN; CARCINOMA; DIFFERENTIATION; MALIGNANCY AB Parathyroid hormone-related peptide (PTHRP) expression and activity were analyzed in normal human ectocervical keratinocytes (HCX) and keratinocytes immortalized by transfection with human papillomavirus (HPV) types 16 and 18 DNAs. In normal cells, trans-retinoic acid (RA) and 2.0 mM Ca2+ significantly stimulated PTHRP mRNA expression and secretion and led to a significant reduction in the rate of proliferation. In contrast, the basal level of PTHRP production decreased sharply in confluent HCX, and induction by Ca2+ or exogenous growth factors was reduced or lost. After stable transfection with HPV16 and HPV18 DNAs, we observed a sharp decrease of PTHRP production in high-passage poorly differentiated HCX. Finally, addition of exogenous PTHRP(1-141) inhibited proliferation of both normal cells and low-passage well-differentiated HPV16 immortalized cells. High-passage poorly differentiated cells were refractory to PTHRP. These results demonstrate that PTHRP production varies greatly with the degree of cell proliferation and differentiation and suggest that this peptide acts as an autocrine negative growth regulator for cervical keratinocytes. C1 MCGILL UNIV, DEPT MED, MONTREAL, PQ H3A 1A1, CANADA. NCI, BIOL LAB, BETHESDA, MD 20892 USA. RP Kremer, R (reprint author), ROYAL VICTORIA HOSP, CALCIUM RES LABS, RM H467, 687 PINE AVE W, MONTREAL, PQ H3A 1A1, CANADA. NR 46 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 1996 VL 271 IS 1 BP C164 EP C171 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UX534 UT WOS:A1996UX53400017 PM 8760042 ER PT J AU Oriji, GK Keiser, HR AF Oriji, GK Keiser, HR TI Action of protein kinase C in endothelin-induced contractions in rat aortic rings SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE 1-(5-isoquinolinesulfonyl)-2-methylpiperazine; 1-(5-isoquinolinesulfonyl)-2-methylpiperazine chloride; staurosporine; phorbol 12,13-dibutyrate; denuded; intact ID SMOOTH-MUSCLE CONTRACTION; CELLS; RECEPTOR; EXPRESSION; INHIBITION; MECHANISMS; MESSENGER; CLONING AB Endothelin (ET) is a potent vasoconstrictor peptide that induces characteristically long-lasting contractions. We used both intact and endothelium-denuded rat aortic rings to investigate the role of protein kinase C (PKC) in ET-induced contractions. ET (10(-9) M) and phorbol 12,13-dibutyrate (PDBu), a PKC activator, produced a gradual and sustained contraction of greater magnitude in denuded aortic rings than in intact rings. When aortic rings were pretreated with graded concentrations of different PKC inhibitors, inhibition of ET-induced contractions began at 10(-9) M and was nearly complete at 10(-3) M, and the reduction was greater in intact than in denuded rings. Pretreatment of aortic rings with PDBu or N-G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, potentiated ET-induced contractions. PKC enzyme assay showed activation of PKC in aortic rings that were treated with either ET or PDBu, inhibition after pretreatment with PKC inhibitors, and no change with 4 alpha-phorbol 12,13-didecanoate (PDD), an inactive phorbol ester. ET significantly increased nitrate and nitrite production, which was further increased by pretreatment with PKC inhibitors. PDBu prevented ET-induced nitrate/nitrite production, and PDD had no effect. These results strongly suggest that PKC mediates, in part, ET-induced contractions in rat aortic rings and that an intact endothelium is required for maximum inhibition by PKC inhibitors because PKC stimulated by ET inhibits nitric oxide release. RP Oriji, GK (reprint author), NHLBI, HYPERTENS ENDOCRINE BRANCH,NIH,BLDG 10,RM 8C103, 10 CTR DR, MSC 1754, BETHESDA, MD 20892 USA. NR 37 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 1996 VL 271 IS 1 BP C398 EP C404 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UX534 UT WOS:A1996UX53400046 PM 8760071 ER PT J AU Sakai, T Ambudkar, IS AF Sakai, T Ambudkar, IS TI Role for protein phosphatase in the regulation of Ca2+ influx in parotid gland acinar cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE calcium entry; manganese entry; protein kinase; okadaic acid; calyculin A; pervanadate; staurosporine; K-252a; salivary acinar cells ID CAPACITATIVE CALCIUM-ENTRY; TYROSINE KINASE INHIBITORS; HUMAN PLATELETS; INOSITOL PHOSPHATE; PLASMA-MEMBRANE; CA-2+ ENTRY; THAPSIGARGIN; ACTIVATION; DEPLETION; MECHANISM AB Stimulation of Ca2+ (and Mn2+) entry in salivary epithelial cells by carbachol, or thapsigargin, is mediated by an, as yet, unknown mechanism that is dependent on the depletion of Ca2+ from intracellular Ca2+ stores. This study assesses the possible role of protein phosphorylation in the regulation of Ca2+ entry in rat parotid gland acinar cells. Treatment of cells with the protein phosphatase inhibitors okadaic acid, calyculin A, and pervanadate induced a dose-dependent inhibition of carbachol and thapsigargin stimulation of Ca2+ and Mn2+ entry. All three inhibitors decreased carbachol stimulation of internal Ca2+ release, which likely accounts for the inhibition of carbachol-stimulated Ca2+ entry. Thapsigargin-induced internal Ca2+ release was not affected by the treatments. Additionally, all three phosphatase inhibitors decreased Mn2+ entry into cells with depleted internal Ca2+ store(s) (achieved by incubation with either carbachol or thapsigargin in Ca2+-free medium). Treatment of cells with phorbol 12-myristate 13-acetate, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, or staurosporine did not affect divalent cation entry into unstimulated cells or thapsigargin-treated cells. Importantly, when cells with depleted internal Ca2+ store(s) were pretreated with staurosporine, or K-252a, the inhibition of Ca2+ entry by calyculin A and okadaic acid, but not by pervanadate, was attenuated. Although the effect of pervanadate remains to be clarified, these results demonstrate a role for protein phosphorylation in the regulation of divalent cation influx in rat parotid acinar cells. C1 NIDR, SECRETORY PHYSIOL SECT, CLIN INVEST & PATIENT CARE BRANCH, NIH, BETHESDA, MD 20892 USA. NR 35 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUL PY 1996 VL 271 IS 1 BP C284 EP C294 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UX534 UT WOS:A1996UX53400032 PM 8760057 ER PT J AU Johren, O Saavedra, JM AF Johren, O Saavedra, JM TI Expression of AT(1A) and AT(1B) angiotensin II receptor messenger RNA in forebrain of 2-wk-old rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE brain angiotensin system; AT(1) receptor subtypes; in situ hybridization; brain development ID TYPE-1 RECEPTOR; SUBFORNICAL ORGAN; HYPERTENSIVE RATS; BRAIN; SUBTYPES; LOCALIZATION; CLONING; INHIBITION; AT1 AB The gene expression of angiotensin II receptor subtypes AT(1A) and AT(1B) was localized in the forebrain of 2-wk-old rats by in situ hybridization histochemistry and compared with [I-125]Sar(1)-angiotensin II binding patterns. AT(1A) receptor mRNA was expressed in circumventricular organs, in hypothalamic nuclei like the paraventricular nucleus, in the lateral olfactory tract, in the basolateral amygdaloid and anterior olfactory nuclei, and in the piriform cortex. No AT(1B) receptor mRNA was detected in these areas. AT(1A) and AT(1B) receptor mRNA was detected in the hippocampus, cingulate cortex, and choroid plexus. No forebrain area studied expressed AT(1B) receptor mRNA exclusively. Most often, a good match for receptor mRNA and binding was found. In some areas, apparent mismatches suggested receptor formation elsewhere (median eminence) or receptor presence in local neuronal circuits (hippocampus, cingulate, and piriform cortex). Our results support the hypothesis that AT(1A) receptors are involved in the classical central functions of angiotensin II. Both AT(1A) and AT(1B) receptors may play roles in cortical and limbic system function, particularly early in development. RP Johren, O (reprint author), NIMH, CLIN SCI LAB,PHARMACOL SECT,10 CTR DR MSC,BLDG 10, RM 2D-45, BETHESDA, MD 20892 USA. RI Johren, Olaf/G-6967-2011 NR 33 TC 60 Z9 60 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 1996 VL 271 IS 1 BP E104 EP E112 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA UW456 UT WOS:A1996UW45600013 PM 8760087 ER PT J AU Mason, RJ McCormickShannon, K Rubin, JS Nakamura, T Leslie, CC AF Mason, RJ McCormickShannon, K Rubin, JS Nakamura, T Leslie, CC TI Hepatocyte growth factor is a mitogen for alveolar type II cells in rat lavage fluid SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE type II cells; acidic fibroblast growth factor; fibroblast growth factor-1 ID STIMULATE DNA-SYNTHESIS; LUNG INJURY; FACTOR RECEPTOR; TREATED RATS; EXPRESSION; PROLIFERATION; REGENERATION; TISSUES; LOCALIZATION; PNEUMOCYTES AB Proliferation of type II cells is required for maintenance of the alveolar epithelium and for restoration after lung injury, Although various known growth factors have been reported to stimulate type LI cell proliferation in vitro, there is very little knowledge on which growth factors are present in the lung in vivo. We have previously reported that rat lavage fluid contains a mitogen(s) for type II cells, and this study was designed to identify the growth factor(s) in this biological fluid for type II cells. The mitogenic activity was purified by sequential chromatography on blue Sepharose and heparin Sepharose. Hepatocyte growth factor (HGF) and acidic fibroblast growth factor were detected in the partially purified lavage fluid by Western analysis. The amount of HGF recovered by lavage was similar to 6 ng/rat. By use of neutralizing antibodies for different growth factors, HGF was found to he responsible for most of the stimulatory activity for rat type a cells in the partially purified lavage fluid. In addition to HGF, rat lavage fluid also contained potent mitogenic activity for fibroblasts. Finally, we have demonstrated that much of the mitogenic activity in salt extracts of human lung is HGF. We conclude that HGF is found in rat lavage fluid and is possibly an important mitogen for adult type II cells in vivo. C1 NATL JEWISH CTR IMMUNOL & RESP MED, DEPT PEDIAT, DENVER, CO 80206 USA. UNIV COLORADO, HLTH SCI CTR, DEPT PATHOL, DENVER, CO 80262 USA. UNIV COLORADO, HLTH SCI CTR, DEPT MED, DENVER, CO 80262 USA. NCI, CELLULAR & MOLEC BIOL LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. OSAKA UNIV, SCH MED, DEPT ONCOL, BIOMED RES CTR, OSAKA 565, JAPAN. RP Mason, RJ (reprint author), NATL JEWISH CTR IMMUNOL & RESP MED, DEPT MED, 1400 JACKSON ST, DENVER, CO 80206 USA. FU NHLBI NIH HHS [HL-29891, HL-27353] NR 30 TC 23 Z9 23 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUL PY 1996 VL 271 IS 1 BP L46 EP L53 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA UX386 UT WOS:A1996UX38600005 PM 8760131 ER PT J AU OsornioVargas, AR Lindroos, PM Coin, PG Badgett, A HernandezRodriguez, NA Bonner, JC AF OsornioVargas, AR Lindroos, PM Coin, PG Badgett, A HernandezRodriguez, NA Bonner, JC TI Maximal PDGF-induced lung fibroblast chemotaxis requires PDGF receptor-alpha SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE platelet-derived growth factor isoforms; platelet-derived growth factor receptors; neomycin; interleukin-1; pulmonary fibrosis; myofibroblasts ID IDIOPATHIC PULMONARY FIBROSIS; GROWTH-FACTOR RECEPTOR; RAT ALVEOLAR MACROPHAGES; SIGNAL TRANSDUCTION; EXPRESSION; BINDING; RELEASE; AA; PROLIFERATION; ISOFORMS AB Alteration of the platelet-derived growth factor (PDGF) receptor system could be important in enhancing the mitogenic and chemotactic potential of lung fibroblasts during pulmonary fibrogenesis. We previously reported that interleukin-1 beta (IL-1 beta) upregulates the PDGF receptor-alpha (PDGFR-alpha) gene, and in this study we sought to establish the importance of the PDGFR-alpha relative to the PDGFR-beta in mediating a chemotactic reponse to PDGF-AA, -AB, and -BB. Pretreatment of fibroblasts for 24 h with IL-1 beta increased chemotaxis to all three PDGF isoforms. IL-1 beta pretreatment markedly increased the maximal number of I-125-labeled PDGF-AA binding sites but did not change the number of I-125-PDGF-AB or PDGF-BB sites. However, IL-1 beta increased I-125-PDGF-AB affinity twofold. Neomycin (5 mM) was used as a PDGFR-alpha antagonist and completely blocked I-125-PDGF-AA binding and PDGF-AA-induced chemotaxis. The binding affinity of I-125-PDGF-AB and I-125-PDGF-BB was increased two- to threefold by neomycin, and chemotaxis to PDGF-AB and PDGF-BB was enhanced. These results define a role for the PDGFR-alpha as a regulatory receptor subtype that is necessary for PDGF isoforms to exert maximal chemotaxis. C1 NIEHS, PULM PATHOBIOL LAB, RES TRIANGLE PK, NC 27709 USA. VET ADM MED CTR, DURHAM, NC 27705 USA. NATL CANC INST, DIV BASIC INVEST, MEXICO CITY 14000, DF, MEXICO. RI Osornio Vargas, Alvaro/D-4012-2009; Osornio Vargas, Alvaro/B-4645-2010 OI Osornio Vargas, Alvaro/0000-0001-8287-7102 NR 31 TC 34 Z9 35 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUL PY 1996 VL 271 IS 1 BP L93 EP L99 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA UX386 UT WOS:A1996UX38600011 PM 8760137 ER PT J AU Devuyst, O Burrow, CR Smith, BL Agre, P Knepper, MA Wilson, PD AF Devuyst, O Burrow, CR Smith, BL Agre, P Knepper, MA Wilson, PD TI Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE water channels; fetal kidney; glycosylation; epithelial polarity; renal cystic tubules ID WATER CHANNEL; COLLECTING DUCT; RAT-KIDNEY; ARGININE VASOPRESSIN; MOLECULAR-CLONING; RENAL CYSTS; MEMBRANE; CHIP; EPITHELIA AB Aquaporin-1 (AQP1), located in proximal tubules (PT) and descending thin limbs of Henle (DTL), and aquaporin-2 (AQP2), located in collecting ducts (CD), are channels involved in water transport across renal tubule epithelia. Using antibodies against AQP1 and AQP2, we here show expression of AQP1 and AQP2 in normal human developing and adult kidneys and in autosomal dominant polycystic kidney disease (ADPKD). Unlike in rats, AQP1 and AQP2 are expressed early during human nephrogenesis (12-wk gestation). AQP1 was first seen in developing PT epithelia, predominantly in apical cell membranes, and, at 15 wk, was also detected in DTL. AQP2 was seen in apical cell membranes of the branching ureteric bud and CD system from 12 wk and throughout development. In adult normal kidneys, AQP1 was localized to apical and basolateral membrane domains of PT and DTL, whereas AQP2 was restricted to principal cells of CD. This distribution of AQP1 and AQP2 was also seen in early stage ADPKD, except that AQP1 was mostly located in the apical membrane region of expanded PT. In end-stage ADPKD, two-thirds of the cysts expressed either AQP1 or AQP2, but these two water channels were never colocalized in the same cyst. Western blot analysis showed maximal expression of AQP1 and AQP2 in normal adult kidneys, lower levels in fetal kidneys, and decreases associated with degree of cystic progression in ADPKD. These data 1) demonstrate specific, mutually exclusive localization of AQP1 and AQP2 in human fetal and adult kidneys; 2) show that both channels are expressed early during nephrogenesis; and 3) show that the mutual exclusivity of localization is maintained even into end-stage ADPKD. C1 JOHNS HOPKINS UNIV, SCH MED, DIV NEPHROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT BIOL CHEM, BALTIMORE, MD 21205 USA. NHLBI, KIDNEY & ELECTROLYTE METAB LAB, NIH, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [HL-48268]; NIDDK NIH HHS [DK-44833] NR 34 TC 86 Z9 88 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD JUL PY 1996 VL 271 IS 1 BP F169 EP F183 PG 15 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA UW458 UT WOS:A1996UW45800025 PM 8760258 ER PT J AU Kishore, BK Terris, JM Knepper, MA AF Kishore, BK Terris, JM Knepper, MA TI Quantitation of aquaporin-2 abundance in microdissected collecting ducts: Axial distribution and control by AVP SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE water channels; arginine vasopressin; enzyme-linked immunosorbent assay; Long-Evans rat; Sprague-Dawley rat ID WATER PERMEABILITY; RAT-KIDNEY; VASOPRESSIN; CHANNEL; RECONSTITUTION; OXYTOCIN; TUBULE; CHIP28 AB Aquaporin-2 (AQP-2) is the arginine vasopressin-regulated water channel of the renal collecting ducts. Using an improved version of a fluorescence-based enzyme-linked immunosorbent assay (Y. Maeda, B. L. Smith, P.Agre, and M. A. Knepper. J. Clin. Invest. 95: 422-428, 1995), we quantified AQP-P protein abundance in microdissected renal collecting ducts from normal Sprague-Dawley (SD) rats and vasopressin-deficient Brattleboro rats. Standard curves were linear in the range of 0-200 fmol/well and were highly reproducible from day to day (lower limit of detection 2.3 fmol; coefficient of variation 6-9%). In SD rats thirsted for 24 h, the measured quantities of AQP-2 were as follows (x10(9) molecules/mm): cortical collecting ducts (CCD), 4.3 +/- 0.5; outer medullary collecting ducts (OMCD), 10.1 +/- 1.7; initial one-third of inner medullary collecting duct (IMCD), 9.2 +/- 1.1; middle one-third of the IMCD (IMCD-8), 7.5 +/- 0.8; terminal one-third of the IMCD ((IMCD-3), 3.3 +/- 0.6; n = 7-12. In IMCD-2 this corresponds to 11.8 +/- 1.3 x 10(6) AQP-2 molecules per cell. Thus AQP-2 is extremely abundant in collecting duct cells. AQP-2 levels were decreased in untreated Brattleboro rats relative to the parent strain Long-Evans (LE) by 68% in IMCD-2 and 44% in CCD. Following vasopressin infusion by osmotic minipumps, AQP-2 levels in IMCD-2 of Brattleboro rats rose gradually, reaching levels equivalent to those seen in LE rats after 5 days. A similar rise was seen in the CCD, indicating that the vasopressin-induced increase was not dependent on a large increase in the interstitial tonicity. Thus a rise in circulating vasopressin concentration increases the level of AQP-2 protein expression in collecting ducts, presumably via a direct action of vasopressin. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PHYSIOL, BETHESDA, MD 20814 USA. NR 33 TC 45 Z9 47 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD JUL PY 1996 VL 271 IS 1 BP F62 EP F70 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA UW458 UT WOS:A1996UW45800011 PM 8760244 ER PT J AU Kwon, ED Dooley, JA Jung, KY Andrews, PM GarciaPerez, A Burg, MB AF Kwon, ED Dooley, JA Jung, KY Andrews, PM GarciaPerez, A Burg, MB TI Organic osmolyte distribution and levels in the mammalian urinary bladder in diuresis and antidiuresis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE glycerophosphocholine; inositol; betaine; sorbitol; urea; bladder epithelium; bladder muscle ID SPECTROSCOPY; EPITHELIUM; UREA AB Inositol, sorbitol, glycerophosphocholine (GPC), and betaine are organic osmolytes that are accumulated by renal medullary cells in response to hyperosmotic stress. Previous screening studies, using nuclear magnetic resonance spectroscopy, have shown some of these same compounds to be present in extracts of whole urinary bladder from rabbits and rats. in the present study, we used highperformance liquid chromatography to quantify levels of these compounds in the separated epithelium and muscle of bladders taken from normal rabbits as well as diuretic and thirsted rats. We find that 1) high concentrations of organic osmolytes, namely inositol, GPC, and sorbitol, are present in urinary bladder; 2) levels of these osmolytes in the bladder epithelium are higher than in the muscle; 3) increased urinary osmolality due to antidiuresis is associated with a 2.4-fold increase in total osmolyte levels in rat bladder epithelium and a lesser (1.5-fold) increase in the muscle, compared with corresponding levels in tissues from diuretic animals; and 4) these increases in total osmolyte amounts in the epithelium are due to increased levels of GPC, sorbitol, and perhaps inositol (P = 0.07), whereas only GPC increases in the bladder muscle. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. NR 13 TC 14 Z9 14 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD JUL PY 1996 VL 271 IS 1 BP F230 EP F233 PG 4 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA UW458 UT WOS:A1996UW45800033 PM 8760266 ER PT J AU Sorensen, G Thompson, B Glanz, K Feng, ZD Kinne, S DiClemente, C Emmons, K Heimendinger, J Probart, C Lichtenstein, E AF Sorensen, G Thompson, B Glanz, K Feng, ZD Kinne, S DiClemente, C Emmons, K Heimendinger, J Probart, C Lichtenstein, E TI Work site-based cancer prevention: Primary results from the Working Well Trial SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID GENERALIZED LINEAR-MODELS; SMOKING CESSATION; QUESTIONNAIRE; RECORDS; INTERVENTION; VALIDATION; WOMEN AB Objectives. This paper presents the behavioral results of the Working well Trial, the largest US work site cancer prevention and control trial to date. Methods. The Working Well Trial used a randomized, matched: pair evaluation design, with the work site as the unit of assignment and analysis. The study was conducted in 111 work sites (n = 28 000 workers). The effects of the intervention were evaluated by comparing changes in intervention and control work sites, as measured in cross-sectional surveys at baseline and follow-up. The 2-year intervention targeted both individuals and the work-site environment. Results. There occurred a net reduction in the percentage of energy obtained from fat consumption of 0.37 percentage points (P = .033), a net increase in fiber densities of 0.13 g/1000 kcal (P = .056), and an average increase in fruit and vegetable intake of 0.18 servings per day (P = .0001). Changes in tobacco use were in the desired direction but were not significant. Conclusions. Significant but small differences were observed for nutrition. Positive trends, but no significant results, were observed in trial-wide smoking outcomes. The observed net differences were small :owing to the substantial secular changes in target behaviors. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. CANC RES CTR HAWAII,HONOLULU,HI 96813. UNIV HOUSTON,HOUSTON,TX 77004. BROWN UNIV,MIRIAM HOSP,PROVIDENCE,RI 02912. NCI,ROCKVILLE,MD. PENN STATE UNIV,DEPT NUTR,UNIVERSITY PK,PA 16802. OREGON RES INST,EUGENE,OR 97403. RP Sorensen, G (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [U01 CA51686, U01 CA51687, U01 CA61771] NR 41 TC 148 Z9 151 U1 0 U2 5 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1996 VL 86 IS 7 BP 939 EP 947 DI 10.2105/AJPH.86.7.939 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UX221 UT WOS:A1996UX22100007 PM 8669517 ER PT J AU Kawachi, I Troisi, RJ Rotnitzky, AG Coakley, EH Colditz, GA AF Kawachi, I Troisi, RJ Rotnitzky, AG Coakley, EH Colditz, GA TI Can physical activity minimize weight gain in women after smoking cessation? SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CIGARETTE-SMOKING; METABOLIC-RATE; BODY-WEIGHT; WITHDRAWAL SYMPTOMS; TOBACCO WITHDRAWAL; RELATIVE WEIGHT; FOOD-INTAKE; QUESTIONNAIRE; REPRODUCIBILITY; NICOTINE AB Objectives. The purpose of this study was to examine prospectively whether exercise can modify weight gain after smoking cessationin women. Methods. Data were analyzed from a 2-year follow-up period (1986-1988) in the Nurses' Health Study, an ongoing cohort of 121 700 US women aged 40 to 75 in 1986. Results. The average weight gain over 2 years was 3.0 kg in the 1474 women who stopped smoking, and 0.6 kg among the 7832 women who continued smoking. Among women smoking 1 to 24 cigarettes per day, those who quit without changing their levels of exercise gained an average of 2.3 kg more (95% confidence interval [CI] = 1.9, 2.6) than women who continued smoking. Women who quit and increased exercise by between 8 to 16 MET-hours (the work metabolic rate divided by the resting metabolic rate) per week gained 1.8 kg (95% CI = 1.0, 2.5), and the excess weight gain was only 1.3 kg (95% CI = 0.7, 1.9) in women who increased exercise by more than 16 MET-hours per week. Conclusions. Smoking cessation is associated with a net excess weight gain of about 2.4 kg in middle-aged women. However, this weight gain is minimized if smoking cessation is accompanied by a moderate increase in the level of physical activity. C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,CHANNING LAB,CAMBRIDGE,MA 02138. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. HARVARD UNIV,DEPT BIOSTAT,CAMBRIDGE,MA 02138. HARVARD UNIV,DEPT EPIDEMIOL,CAMBRIDGE,MA 02138. RP Kawachi, I (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH & SOCIAL BEHAV,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 40356]; NIDDK NIH HHS [DK 46200] NR 37 TC 71 Z9 73 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1996 VL 86 IS 7 BP 999 EP 1004 DI 10.2105/AJPH.86.7.999 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UX221 UT WOS:A1996UX22100015 PM 8669525 ER PT J AU Weed, DL AF Weed, DL TI The future of epidemiology: A humanist response - Response SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID CESSATION; BEHAVIORS; SMOKING RP Weed, DL (reprint author), NCI,PREVENT ONCOL BRANCH,EPS T-41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1996 VL 86 IS 7 BP 1029 EP 1030 DI 10.2105/AJPH.86.7.1029-a PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UX221 UT WOS:A1996UX22100022 ER PT J AU Moss, N AF Moss, N TI Sexual attitudes and lifestyles - Johnson,AM, Wadsworth,J, Wellings,K, Field,J SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Book Review RP Moss, N (reprint author), NIA,BEHAV & SOCIAL RES PROGRAM,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1996 VL 86 IS 7 BP 1037 EP 1039 DI 10.2105/AJPH.86.7.1037 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UX221 UT WOS:A1996UX22100030 ER PT J AU Moss, N AF Moss, N TI The social organization of sexuality: Sexual practices in the United States - Laumann,EO, Gagnon,JH, Michael,RT, Michaels,S SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Book Review RP Moss, N (reprint author), NIA,BEHAV & SOCIAL RES PROGRAM,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1996 VL 86 IS 7 BP 1037 EP 1039 DI 10.2105/AJPH.86.7.1037 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UX221 UT WOS:A1996UX22100029 ER PT J AU Cain, VS AF Cain, VS TI Review: Sexual behavior and AIDS - Spira,A, Bajos,N SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Book Review RP Cain, VS (reprint author), NIH,OFF BEHAV & SOCIAL SCI RES,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1996 VL 86 IS 7 BP 1039 EP 1040 DI 10.2105/AJPH.86.7.1039 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UX221 UT WOS:A1996UX22100031 ER PT J AU Eichacker, PQ Hoffman, WD Danner, RL Banks, SM Richmond, S Fitz, Y Natanson, C AF Eichacker, PQ Hoffman, WD Danner, RL Banks, SM Richmond, S Fitz, Y Natanson, C TI Serial measures of total body oxygen consumption in an awake canine model of septic shock SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CRITICALLY ILL PATIENTS; SUPPLY DEPENDENCY; DELIVERY; SEPSIS; DYSFUNCTION; DOBUTAMINE; FAILURE; PATHOGENESIS; METABOLISM; BACTEREMIA AB We examined serial changes in total body oxygen consumption (Vo(2)) in a permanently tracheotomized canine sepsis model. On Day 0, beagles had an Escherichia coli-infected (septic) or sterile (control) clot surgically placed in the peritoneum. During the 21-d study, 10 of the 16 septic animals and none of the six control animals died (p = 0.02). After clot placement septic versus control animals had decreased mean arterial blood pressure (mm Hg; Day 1: 106 versus 128, p = 0.055; Day 2: 95 versus 125, p = 0.004, respectively) and left ventricular ejection fraction (Day 1 : 0.44 versus 0.69, p = 0.0006; Day 2: 0.33 versus 0.57, p = 0.0001, respectively). Despite significant lethality and cardiovascular dysfunction, in the septic group on Days 1 and 2, septic versus control animals had no significant differences in mean metabolic cart measured (Vo(2)DIR, ml/kg/min; Day 1: 11.9 versus 12.4, p = 0.81; Day 2: 14.2 versus 13.5, p = 0.72, respectively) and intravascular catheter calculated (Vo(2)INDIR, ml/kg/min; Day 1: 11.2 versus 11.2, p = 0.99; Day 2: 12.8 versus 15.4, p = 0.49, respectively). On Day 1 in septic and control animals, volume infusion produced increases (p < 0.001) in oxygen delivery (Do(2)). In septic and control animals these changes in Do(2) were similar and were associated with similar increases in Vo(2)DIR (p = 0.001), and Vo(2)INDIR (p = 0.001). In fact, at all time points studied (baseline, Day 1, 2, and 21), both before and after volume infusion, levels of Do(2), Vo(2)DIR, and Vo(2)INDIR did not differ between septic and control animals, nor did they differ between septic survivors and nonsurvivors. Because levels of Vo(2)DIR and Vo(2)INDIR were similar in both groups, we pooled data from septic and control animals. Throughout the study, Vo(2) showed a moderate association with Vo(2)INDIR (r = 0.55, p = 0.003), but mean Vo(2)DIR was lower at baseline (p = 0.001) and on Day 21 (p = 0.07) and greater on Day 2 (p < 0.01). In summary, our techniques, which detected small changes in both Vo(2)DIR and Vo(2)INDIR occurring with volume infusion, did not demonstrate differences in these parameters comparing control and septic animals. These results in euvolemic septic animals suggest that total body Vo(2) may not reflect pathogenetic mechanisms during sepsis and septic shock. Furthermore, these results suggest that although the level of total body Vo(2) may reflect the effects of therapeutic interventions such as volume loading, it should not itself serve as a therapeutic target. 7 C1 ARMED FORCES RADIOBIOL RES INST,DEF NUCL AGCY,BETHESDA,MD. RP Eichacker, PQ (reprint author), NIH,DEPT CRIT CARE MED,CTR CLIN,BLDG 10,ROOM 10D48,BETHESDA,MD 20892, USA. NR 37 TC 9 Z9 9 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL PY 1996 VL 154 IS 1 BP 68 EP 75 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA UW827 UT WOS:A1996UW82700013 PM 8680702 ER PT J AU Kaplan, JE Hu, DJ Holmes, KK Jaffe, HW Masur, H DeCock, KM AF Kaplan, JE Hu, DJ Holmes, KK Jaffe, HW Masur, H DeCock, KM TI Preventing opportunistic infections in human immunodeficiency virus-infected persons: Implications for the developing world SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Review ID PNEUMOCYSTIS-CARINII PNEUMONIA; PENICILLIUM-MARNEFFEI INFECTION; PLASMODIUM-FALCIPARUM MALARIA; IMMUNE-DEFICIENCY-SYNDROME; HIV-INFECTION; RANDOMIZED TRIAL; AIDS PATIENTS; AEROSOLIZED PENTAMIDINE; DEVELOPING-COUNTRIES; KAPOSIS-SARCOMA AB More than 18 million persons in the world are estimated to have been infected with human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). As immunodeficiency progresses, these persons become susceptible to a wide variety of opportunistic infections (OIs) The spectrum of OIs varies among regions of the world. Tuberculosis is the most common serious OI in sub-Saharan Africa and is also more common in Latin America and in Asia than in the United States. Bacterial and parasitic infections are prevalent in Africa; protozoal infections such as toxoplasmosis, cryptosporidiosis, and isosporiasis are also common in Latin America. Fungal infections, including cryptococcosis and Penicillium marneffei infection, appear to be prevalent in Southeast Asia. Despite limited health resources in these regions, some measures that are recommended to prevent OIs in the United States may be useful for prolonging and improving the quality of life of HIV-infected persons. These include trimethoprim-sulfamethoxazole to prevent Pneumocystis carinii pneumonia, toxoplasmosis, and bacterial infections; isoniazid to prevent tuberculosis; and 23-valent pneumococcal vaccine to prevent disease due to Streptococcus pneumoniae. Research is needed to determine the spectrum of OIs and the efficacy of various prevention measures in resource-poor nations, and health officials need to determine a minimum standard of care for HIV-infected persons. An increasing problem in the developing world, HIV/AIDS should receive attention comparable to other tropical diseases. C1 CTR DIS CONTROL & PREVENT,DIV AIDS STD & TB LAB RES,NATL CTR INFECT DIS,ATLANTA,GA 30333. UNIV WASHINGTON,CTR AIDS & STD,SEATTLE,WA 98122. NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. RP Kaplan, JE (reprint author), CTR DIS CONTROL & PREVENT,DIV HIV AIDS PREVENT,NATL CTR HIV STD & TB PREVENT,MAILSTOP G-29,ATLANTA,GA 30333, USA. NR 113 TC 73 Z9 75 U1 2 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUL PY 1996 VL 55 IS 1 BP 1 EP 11 PG 11 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA VA963 UT WOS:A1996VA96300001 PM 8702012 ER PT J AU Nozaki, T Engel, JC Dvorak, JA AF Nozaki, T Engel, JC Dvorak, JA TI Cellular and molecular biological analyses of nifurtimox resistance in Trypanosoma cruzi SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID TRYPANOTHIONE REDUCTASE; ESCHERICHIA-COLI; NITROFURAZONE RESISTANCE; PLASMODIUM-FALCIPARUM; OXIDATIVE STRESS; STRAINS; GENES; CHEMOTHERAPY; SENSITIVITY; PHENOTYPE AB We induced nifurtimox resistance in both epimastigotes and tissue culture-derived trypomastigotes of several Trypanosoma cruzi strains. The magnitude of nifurtimox resistance was strain-dependent. A variety of karyotype changes occurred in the nifurtimox-resistant (NR) strains. Chromosome-specific DNA probes identified karyotype changes common to the NR strains that were moderately resistant to nifurtimox but not the NR strains that were highly resistant to nifurtimox. A marked increase in nifurtimox resistance in one NR strain was accompanied by a 100% increase in nuclear DNA mass and a 50% increase in kinetoplast DNA mass. These data suggest that nifurtimox resistance can be accompanied by a wide spectrum of DNA changes. Both trypanothione reductase and heat-shock proteins may modulate the effects of exposure of T. cruzi to nifurtimox. However, we did not detect qualitative or quantitative differences in these genes or their transcripts between the NR strains and the sensitive strains from which they were derived. An understanding of the spectrum of diversity in nifurtimox resistance at the cellular and molecular levels demonstrated in this report is critical in the development of drug therapies against Chagas' disease. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. NR 34 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUL PY 1996 VL 55 IS 1 BP 111 EP 117 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA VA963 UT WOS:A1996VA96300019 PM 8702014 ER PT J AU Cook, JA Kim, SY Teague, D Krishna, MC Pacelli, R Mitchell, JB Vodovotz, Y Nims, RW Christodoulou, D Miles, AM Grisham, MB Wink, DA AF Cook, JA Kim, SY Teague, D Krishna, MC Pacelli, R Mitchell, JB Vodovotz, Y Nims, RW Christodoulou, D Miles, AM Grisham, MB Wink, DA TI Convenient colorimetric and fluorometric assays for S-nitrosothiols SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID NITRIC-OXIDE; RELAXING FACTOR; GUANYLATE-CYCLASE; ESCHERICHIA-COLI; NITROSATION; OXIDATION; KINETICS; NITROSYLATION; INVOLVEMENT; ACTIVATION AB S-nitrosothiols have been shown to affect a number of physiological: functions, Several techniques have been used to detect these species in biological systems, primarily by methods utilizing chemiluminescence, since the apparatus required far measurement of chemiluminescence are not readily available in mast laboratories, methods employing more conventional techniques such as uv-vis and fluorescence spectroscopy may be of greater use, Herein, we report the development of colorimetric and fluorometric methods for the reliable quantitation of S-nitrosothiols, Solutions containing sulfanilamide/N-(1-naphthyl)-ethylenediamine dihydrochloride or 2,2'-azinobis (3-ethylbenzthiazoline-6-sulfonic acid), when exposed to S-nitrosoglutathione (GSNO), S-nitrosocysteine, or S-nitrosoacteylpenicillamine, resulted in no absorbance changes in the range of 400-800 nm. Exposure to HgCl2 or Cu(acetate)(2) resulted in release of nitric oxide (NO) from the S-nitrosothiols. The liberated NO reacted subsequently with oxygen and formed a chemical species which reacted with either analysis solution, resulting in an increase in absorption between 400 and 8OO nm, A plot of RSNO versus absorbance was linear for both mercury(PI) and copper(IH) ions where the slope in the presence of mercury ion was significantly greater than that for copper ion, The Sensitivity was as low as 5 mu M RSNO using HgCl2. The fluorometric method using 2,3-diaminonaphthalene as the scavenger of the NO/O-2 products gave a sensitivity of 50 nM for GSNO. In addition, S-nitrosylated proteins were quantitated using the fluorometric technique, These methods provide accurate determination of low concentrations of S-nitro-sothiols, utilizing conventional spectroscopic techniques available in most laboratories, (C) 1996 Academic Press, Lac. C1 NCI,RADIAT BIOL BRANCH,TUMOR BIOL SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. GRAMBLING STATE UNIV,DEPT CHEM,GRAMBLING,LA 71241. LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,SHREVEPORT,LA 71130. NR 38 TC 131 Z9 137 U1 1 U2 13 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 1 PY 1996 VL 238 IS 2 BP 150 EP 158 DI 10.1006/abio.1996.0268 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UW720 UT WOS:A1996UW72000007 PM 8660604 ER PT J AU Cohen, PJ AF Cohen, PJ TI Single versus multiple sites and mechanisms of inhaled anesthetics SO ANESTHESIA AND ANALGESIA LA English DT Letter ID PRESSURE RP Cohen, PJ (reprint author), NIDA,ROCKVILLE,MD 20857, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 1996 VL 83 IS 1 BP 205 EP 205 PG 1 WC Anesthesiology SC Anesthesiology GA UT702 UT WOS:A1996UT70200068 ER PT J AU Ved, SA Walden, TL Montana, J Lea, DE Tefft, MC Kataria, BK Pudimat, MA Nicodemus, HF Milmoe, GJ AF Ved, SA Walden, TL Montana, J Lea, DE Tefft, MC Kataria, BK Pudimat, MA Nicodemus, HF Milmoe, GJ TI Vomiting and recovery after outpatient tonsillectomy and adenoidectomy in children - Comparison of four anesthetic techniques using nitrous oxide with halothane or propofol SO ANESTHESIOLOGY LA English DT Article DE anesthesia, outpatient; anesthesia, pediatric, otolaryngologic; anesthetics, intravenous, propofol; anesthetics, volatile, halothane; complications, postoperative vomiting; surgery, adenoidectomy, otolaryngologic, tonsillectomy ID STRABISMUS SURGERY; PEDIATRIC OUTPATIENTS; EMESIS AB Background: The authors' purpose in this study was to compare prospectively four different anesthetic induction and maintenance techniques using nitrous oxide with halothane and/or propofol for vomiting and recovery after outpatient tonsillectomy and adenoidectomy procedures in children. Methods: Eighty unpremedicated children, aged 3-10 yr, were assigned randomly to four groups: group H/H, 0.5-2% halothane induction/halothane maintenance; group P/P, 3-5 mg . kg(-1) propofol induction and 0.1-0.3 mg . kg(-1) . min(-1) propofol maintenance; group H/P, 0.1-0.3 mg . kg(-1) . min(-1) halothane induction/propofol maintenance; and group P/H, 3-5 mg . kg(-1) propofol induction and 0.5-2% halothane maintenance, Nitrous oxide (67%) and oxygen (33%) were administered in all the groups. Other treatments and procedures were standardized intra- and postoperatively, Results of postoperative vomiting and recovery were analyzed in the first 6 h and beyond 6 h. Results: Logistic regression showed that vomiting occurred 3.5 times as often when halothane was used for maintenance of anesthesia (groups H/H and P/H) compared with the use of propofol (groups P/P and H/P; Odds Ratio 3.5; 95% confidence interval 1.3 and 9.4, respectively; P = 0.012), A significant association between vomiting (< 6 h: yes/no) and discharge times (> 6 h: yes/no) (Odd's Ratio = 3.6; 95% confidence interval: 1.02, 12.4, respectively) (P = 0.046) was shown, However, no significant differences among the groups in the incidence of vomiting beyond 6 h, recurrent vomiting, or hospital discharge times were shown. Conclusions: After tonsillectomy and adenoidectomy procedures, despite reduced postoperative vomiting with use of propofol rather than halothane, along with nitrous oxide for anesthetic maintenance, the authors found no differences in ''true'' endpoints such as unplanned admissions or discharge times, Among the groups, the main factor that delayed hospital discharge beyond 6 h was vomiting within the first 6 h. C1 NCI,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20007. RP Ved, SA (reprint author), GEORGETOWN UNIV,MED CTR,DEPT ANESTHESIA,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 16 TC 30 Z9 31 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1996 VL 85 IS 1 BP 4 EP 10 DI 10.1097/00000542-199607000-00002 PG 7 WC Anesthesiology SC Anesthesiology GA UW186 UT WOS:A1996UW18600004 PM 8694380 ER PT J AU RealiForster, C Kolobow, T Giacomini, M Hayashi, T Horiba, K Ferrans, VJ AF RealiForster, C Kolobow, T Giacomini, M Hayashi, T Horiba, K Ferrans, VJ TI New endotracheal tube cuff recalls past efforts: Focuses on laryngeal placement - Reply SO ANESTHESIOLOGY LA English DT Letter RP RealiForster, C (reprint author), NHLBI,IR PB,NIH,BLDG 10,ROOM 5D17,10 CTR DR,MSC 1412,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 1996 VL 85 IS 1 BP 222 EP 222 DI 10.1097/00000542-199607000-00035 PG 1 WC Anesthesiology SC Anesthesiology GA UW186 UT WOS:A1996UW18600037 ER PT J AU Kimm, SYS Obarzanek, E Barton, BA Aston, CE Similo, SL Morrison, JA Sabry, ZI Schreiber, GB McMahon, RP AF Kimm, SYS Obarzanek, E Barton, BA Aston, CE Similo, SL Morrison, JA Sabry, ZI Schreiber, GB McMahon, RP TI Race, socioeconomic status, and obesity in 9- to 10 year-old girls: The NHLBI Growth and Health Study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE obesity; socioeconomic status; race; girls; poverty; African-Americans; television; caloric intake ID CHILDHOOD OBESITY; PHYSICAL-ACTIVITY; GENETIC-ASPECTS; METABOLIC-RATE; BLACK-WOMEN; CHILDREN; TELEVISION; FATNESS; EDUCATION; ETHNICITY AB The purpose of this investigation was to determine whether measures of socioeconomic status (SES) are inversely associated with obesity in 9- to 10-year-old black and white girls and their parents. Subjects were participants in the Growth and Health Study (NGHS) of the National Heart, Lung, and Blood Institute. Extensive SES, anthropometric, and dietary data were collected at baseline on 2379 NGHS participants. The prevalence of obesity was examined in the NGHS girls and parents in relation to SES and selected environmental factors. Less obesity was observed at higher levels of household income and parental education in white girls but not in black girls. Among the mothers of the NGHS participants who were seen, lower prevalence of obesity was observed with higher levels of income and education for white mothers, but no consistent patterns were seen in black mothers. Univariate logistic models indicated that the Prevalence of obesity was significantly and inversely associated with parental income and education and number of parents in the household in white girls whereas caloric intake and TV viewing were significantly and positively associated with obesity. Among black girls, only TV viewing was significantly and positively associated with the prevalence of obesity. Multivariate logistic regression models revealed that lower parental educational attainment, one-parent household, and increased caloric intake were significantly associated with the prevalence of obesity in white girls; for black girls, only increased hours of TV viewing were significant in these models. It is concluded that socioeconomic status, as measured by education and income, was related to the prevalence of obesity in girls, with racial variation in these associations. A lower prevalence of obesity was seen at higher levels of socioeconomic status in white girls, whereas no clear relationship was detected in black girls. These findings raise new questions regarding the correlates of obesity in black girls. Ann Epidemiol 1996; 266-275. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,NIH,BETHESDA,MD 20892. MARYLAND MED RES INST,BALTIMORE,MD. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT HUMAN GENET,PITTSBURGH,PA 15261. CHILDRENS HOSP,MED CTR,CINCINNATI,OH 45229. WESTAT CORP,ROCKVILLE,MD 20850. UNIV CALIF BERKELEY,BERKELEY,CA 94720. RP Kimm, SYS (reprint author), UNIV PITTSBURGH,SCH MED,DEPT FAMILY MED & CLIN EPIDEMIOL,M-200 SCAIFE HALL,PITTSBURGH,PA 15261, USA. RI McMahon, Robert/C-5462-2009; OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [N0-HC-55023-26] NR 44 TC 86 Z9 86 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 1996 VL 6 IS 4 BP 266 EP 275 DI 10.1016/S1047-2797(96)00056-7 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VF009 UT WOS:A1996VF00900003 PM 8876836 ER PT J AU Jonas, HA Kronmal, RA Psaty, BM Manolio, TA Meilahn, EN Tell, GS Tracy, RP Robbins, JA AntonCulver, H AF Jonas, HA Kronmal, RA Psaty, BM Manolio, TA Meilahn, EN Tell, GS Tracy, RP Robbins, JA AntonCulver, H TI Current estrogen-progestin and estrogen replacement therapy in elderly women: Association with carotid atherosclerosis SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE atherosclerosis; carotid arterial wall thickness; carotid stenosis; estrogen replacement therapy; combined extrogen/progestin replacement therapy; elderly women ID CORONARY-ARTERY DISEASE; POSTMENOPAUSAL WOMEN; RISK-FACTORS; CARDIOVASCULAR HEALTH; HEART-DISEASE; MYOCARDIAL-INFARCTION; ENDOMETRIAL CANCER; LIPOPROTEINS; ESTRADIOL; INHIBITION AB The cardioprotective effects of combined estrogen/progestin replacement therapy have been questioned. Therefore, we have compared carotid arterial wall thickening and the prevalence of carotid stenosis in elderly women (greater than or equal to 65 years old) currently using replacement estrogen/progestins (E+P) with arterial pathology and its prevalence in women using unopposed estrogens (E). This cross-sectional study used baseline data from all 2962 women participating in the Cardiovascular Health Study, a population-based study of coronary heart disease and stroke in elderly adults. Users of hormone replacement therapy (HRT) were categorized as never (n = 1726), past (n = 787), current E (n = 280), or current E+P (n = 73). Maximal intimal-medial thicknesses of the internal and common carotid arteries and stenosis of the internal carotid arteries were measured by ultrasonography. Current E+P users resembled current E users in most respects, although some lifestyle factors were more favorable among E+P users. Current ESP use and current E use (as compared with no use) were associated with smaller internal carotid wall thicknesses (-0.22 mm; P = 0.003; and -0.09 mm; P = 0.05, respectively) and smaller common carotid wall thicknesses (-0.05 mm; P = 0.03; and -0.02 mm; P = 0.1, respectively) and lower odds ratios (OR) for carotid stenosis (greater than or equal to 1% vs. 0%); OR = 0.61; 95% confidence interval [CI]: 0.36 to 1.01; and OR = 0.91, 95% CI: 0.67 to 1.24, respectively, after adjustment for current lifestyle and risk factors. When both groups of current HRT users were compared, there were no significant differences in carotid wall thicknesses or prevalence of carotid stenosis. For this sample of elderly women, both current E+P therapy and current E therapy were associated with decreased measures of carotid atherosclerosis. These measures did not differ significantly between the two groups of HRT users. Ann Epidemiol 1996; 6:314-323. C1 LA TROBE UNIV,CTR STUDY MOTHERS & CHILDRENS HLTH,MELBOURNE,VIC,AUSTRALIA. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV LONDON LONDON SCH HYG & TROP MED,DEPT EPIDEMIOL,LONDON WC1E 7HT,ENGLAND. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. UNIV CALIF IRVINE,DEPT MED,DIV EPIDEMIOL,IRVINE,CA 92717. UNIV CALIF DAVIS,DEPT MED,SACRAMENTO,CA 95817. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 FU PHS HHS [N01-807079, N01-807080, N01-807081] NR 52 TC 40 Z9 41 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUL PY 1996 VL 6 IS 4 BP 314 EP 323 DI 10.1016/S1047-2797(96)00048-8 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VF009 UT WOS:A1996VF00900009 PM 8876842 ER PT J AU Broxmeyer, HE Cooper, S Li, ZH Lu, L Sarris, A Wang, MH Chang, MS Donner, DB Leonard, EJ AF Broxmeyer, HE Cooper, S Li, ZH Lu, L Sarris, A Wang, MH Chang, MS Donner, DB Leonard, EJ TI Macrophage-stimulating protein, a ligand for the RON receptor protein tyrosine kinase, suppresses myeloid progenitor cell proliferation and synergizes with vascular endothelial cell growth factor and members of the chemokine family SO ANNALS OF HEMATOLOGY LA English DT Article DE macrophage-stimulating protein; vascular endothelial cell growth factor; chemokines; progenitor cells; suppressive synergism ID UMBILICAL-CORD BLOOD; INTERFERON-INDUCIBLE PROTEIN-10; HUMAN BONE-MARROW; HEMATOPOIETIC PROGENITORS; COLONY FORMATION; PEPTIDE ENA-78; GENE-PRODUCT; FLT3 LIGAND; LINE; CYTOKINES AB Macrophage-stimulating protein (MSP), originally identified as an inducer of murine resident macrophage responsiveness to chemoattractants, is a ligand for human RON/murine STK receptor protein tyrosine kinases. Since STK was cloned from populations enriched for hematopoietic stem cells, we initiated studies on the effects of MSP on colony formation by granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) myeloid progenitor cells. MSP alone had no colony stimulating activity. However, MSP caused about a 50% suppression of CFU-GM colony formation induced by synergistic combinations of SLF or Flt-L plus GM-CSF, G-CSF, or IL-3 and of BFU-E and CFU-GEMM colonies induced by SLF or Flt3-L plus Epo or Epo and IL-3. In contrast, MSP had no effect on progenitors stimulated by one growth factor. MSP also suppressed colony formation by stimulated cord blood progenitors, but only after preinduction to a rapidly cycling state. It was previously reported that several members of the chemokine family synergistically suppress myeloid progenitor proliferation. Likewise, synergistic suppression was observed when MSP was paired with VEGF, MIP-1 alpha, IL-8, PF4, MCP-1, IP-10, or ENA-78, or when VEGF was paired with the chemokines; and the required MSP concentration was more than 100-fold less than for MSP alone. Additionally, MSP or VEGF inhibited proliferation of the human myeloid growth factor-dependent cell line, M07e, but a sustained effect required multiple additions over time. At the least, some of the MSP suppressive effects on myeloid progenitors, as assessed on single isolated CD34(+++) marrow cells, appeared to be directly on the progenitors; sustained additions of MSP were required to see this effect. The suppressive action of MSP and its synergism with proteins of the chemokine family may be of relevance to regulation of blood cell production. C1 INDIANA UNIV,SCH MED,DEPT MED HEMATOL ONCOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT IMMUNOL MICROBIOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT PHYSIOL BIOPHYS,INDIANAPOLIS,IN 46202. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,LYMPHONA SECT,HOUSTON,TX. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. AMGEN CORP,THOUSAND OAKS,CA 91320. RP Broxmeyer, HE (reprint author), INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,975 W WALNUT ST,ROOM 501,INDIANAPOLIS,IN 46202, USA. FU NCI NIH HHS [R3T CA36464]; NHLBI NIH HHS [R01 HL46549, R01 HL54037] NR 35 TC 27 Z9 29 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD JUL PY 1996 VL 73 IS 1 BP 1 EP 9 DI 10.1007/s002770050192 PG 9 WC Hematology SC Hematology GA UZ292 UT WOS:A1996UZ29200001 PM 8695717 ER PT J AU Gibril, F Reynolds, JC Doppman, JL Chen, CC Venzon, DJ Termanini, B Weber, C Stewart, CA Jensen, RT AF Gibril, F Reynolds, JC Doppman, JL Chen, CC Venzon, DJ Termanini, B Weber, C Stewart, CA Jensen, RT TI Somatostatin receptor scintigraphy: Its sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas - A prospective study SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE receptors, somatostatin; neoplasm metastasis; gastrinoma; radionuclide imaging; Zollinger-Ellison syndrome ID ZOLLINGER-ELLISON SYNDROME; IN-111 OCTREOTIDE SCINTIGRAPHY; ISLET CELL TUMORS; ENDOCRINE TUMORS; GASTROENTEROPANCREATIC TUMORS; NEUROENDOCRINE TUMORS; AGGRESSIVE RESECTION; MALIGNANT GASTRINOMA; LOCALIZATION; MANAGEMENT AB Objective: To compare the sensitivity of somatostatin receptor scintigraphy done using [In-111-DTPA-DPhe(1)]octreotide with that of other imaging methods in the localization of gastrinomas in patients with the Zollinger-Ellison syndrome. Design: Prospective study. Setting: Referral-based clinical research center. Patients: 80 consecutive patients with the Zollinger-Ellison syndrome. Interventions: Conventional tumor localization studies (ultrasonography, computed tomography [CT], magnetic resonance imaging [MRI], selective angiography, and bone scanning) and somatostatin receptor scintigraphy done using [In-111-DTPA-DPhe(1)]octreotide with single-photon emission CT imaging at 4 and 24 hours. Patients with possible liver metastases had biopsies done for confirmation, and 15 patients had exploratory laparotomies done to assess primary tumor localization. Results: Extrahepatic gastrinomas or liver metastases were identified by ultrasonography in 19% of patients, by CT in 38% of patients, by MRI in 45% of patients, by angiography in 40% of patients, and by somatostatin receptor scintigraphy in 70% of patients. Somatostatin receptor scintigraphy was as sensitive as the other tests combined (59%), and when the results of all other tests were added to the somatostatin receptor scintigraphy results, tumors were localized in 75% of patients. Among patients with a possible primary tumor, the results of ultrasonography were positive in 9%, the results of CT were positive in 31%, the results of MRI were positive in 30%, the results of angiography were positive in 28%, and the results of somatostatin receptor scintigraphy were positive in 58%. Somatostatin receptor scintigraphy was as sensitive as all of the other imaging studies combined; when the results of scintigraphy were added to the results of the other studies, possible primary tumors were identified in 68% of patients. In 24 patients who had histologically proven metastatic liver disease, sensitivities for the detection of any metastatic liver lesions were 46% for ultrasonography, 42% for CT, 71% for MRI, 62% for angiography, and 92% for somatostatin receptor scintigraphy. Somatostatin receptor scintigraphy was significantly better than all of the conventional imaging methods in the identification of gastrinomas later found at surgery (P = 0.004), but it still missed 20% of gastrinomas. Conclusions: Somatostatin receptor scintigraphy is the single most sensitive method for imaging either primary or metastatic liver lesions in patients with the Zollinger-Ellison syndrome. Because of its sensitivity, simplicity, and cost-effectiveness, it should be the first imaging method used in these patients. For patients with negative results on somatostatin receptor scintigraphy, guidelines about the use of other imaging studies are proposed. C1 NIDDK,NIH,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,NIH,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 53 TC 321 Z9 326 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 1 PY 1996 VL 125 IS 1 BP 26 EP & PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA UT399 UT WOS:A1996UT39900004 PM 8644985 ER PT J AU Cervenakova, L Sivakumar, K Nagle, J Dalakas, MC Goldfarb, LG AF Cervenakova, L Sivakumar, K Nagle, J Dalakas, MC Goldfarb, LG TI Is hereditary inclusion body myopathy a ''familial prion disease''? SO ANNALS OF NEUROLOGY LA English DT Letter ID MYOSITIS; PROTEIN; MUSCLE C1 NINCDS,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. RP Cervenakova, L (reprint author), NINCDS,CNS STUDIES LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1996 VL 40 IS 1 BP 128 EP 128 DI 10.1002/ana.410400122 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UW805 UT WOS:A1996UW80500021 PM 8687183 ER PT J AU Yarboro, CH Wesley, R Amantea, MA Klippel, JH Pucino, F AF Yarboro, CH Wesley, R Amantea, MA Klippel, JH Pucino, F TI Modified oral ondansetron regimen for cyclophosphamide-induced emesis in lupus nephritis SO ANNALS OF PHARMACOTHERAPY LA English DT Article ID CHEMOTHERAPY; EFFICACY; DEXAMETHASONE; GR38032F; NAUSEA; TRIAL AB OBJECTIVE: To evaluate the antiemetic efficacy of a modified regimen of oral ondansetron and dexamethasone in patients with lupus nephritis undergoing treatment with cyclophosphamide whose conventional antiemetic regimen had failed. DESIGN: A before-after prospective observational pilot project. SETTING: A federal research hospital. PATIENTS: Fourteen outpatients with lupus nephritis receiving intravenous cyclophosphamide 0.75-1.0 g/m(2) had previously experienced chemotherapy-induced emetic events (vomiting or retching) while receiving a standard combination intravenous antiemetic regimen. The regimen consisted of four doses of thiethylperazine 10 mg and diphenhydramine 25 mg every 6 hours, and two doses of lorazepam 0.5 mg every 6 hours starting 1 hour prior to cyclophosphamide. A subset of 8 patients previously completed a blinded study in which they received the intravenous formulation of ondansetron (4 doses of 4-16 mg q4h) administered orally beginning 30 minutes prior to the cyclophosphamide infusion. MAIN OUTCOME MEASURES: The number of emetic events and cost of drug administration were assessed for the modified ondansetron intervention and compared with those of the standard antiemetic regimen. The incidence of emetic events and visual analog nausea scores for the subset of eight patients were also evaluated. aa: TO account for the delayed onset of emesis associated with cyclophosphamide, patients received both ondansetron 8 mg orally every 4 hours (3 doses) and dexamethasone 10 mg orally (1 dose) beginning 4 hours after the cyclophosphamide infusion. This is different from the manufacturer's recommended dose schedule,in which ondansetron is administered prior to chemotherapy, RESULTS: NO emetic events were observed following the administration of oral ondansetron/dexamethasone. The 95% confidence interval for the bur rate of emesis was 0% to 19.3%. There was a significant difference in efficacy between ondansetron/dexamethasone and the triple antiemetic regimen (p < 0.0002). None of the patients experienced adverse effects while receiving the ondansetron/dexamethasone regimen. Cost comparisons (including admixture and nursing administration times) for standard combination therapy and oral ondansetron/dexamethasone were $109.09 and $70.24, respectively. No difference in emetic events or nausea ratings was observed between oral ondansetron/dexamethasone tablets and oral administration of ondansetron using the intravenous formulation. CONCLUSIONS: This study suggests that a modified oral ondansetron/dexamethasone regimen is safe and efficacious, and costs less than alternative regimens to prevent cyclophosphamide-induced emesis in patients with lupus nephritis. C1 NIH,DEPT PHARM,BETHESDA,MD 20892. NIAMSD,NIH,BETHESDA,MD. NIH,MED INFORMAT SYST DEPT,BETHESDA,MD 20892. SEA QUEST PHARMACEUT,PHARMACOKINET,SAN DIEGO,CA. NR 15 TC 7 Z9 8 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 1996 VL 30 IS 7-8 BP 752 EP 755 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UX713 UT WOS:A1996UX71300008 PM 8826554 ER PT J AU Greiner, JW Guadagni, F Roselli, M Nieroda, CA AF Greiner, JW Guadagni, F Roselli, M Nieroda, CA TI Novel approaches to tumor detection and therapy using a combination of monoclonal antibody and cytokine SO ANTICANCER RESEARCH LA English DT Article DE immunodiagnosis; gamma-interferon; gamma-detecting probe; radioimmunotherapy ID SINGLE-CHAIN FV; CARCINOEMBRYONIC ANTIGEN EXPRESSION; RADIOIMMUNOGUIDED SURGERY; GAMMA-INTERFERON; COLORECTAL-CANCER; CELLS; RADIOIMMUNODETECTION; GENE AB Cytokine-based tumor antigen augmentation is one of the approaches researchers and clinicians are using to improve the effectiveness of MAb-directed tumor diagnosis and therapy. Other efforts encompass the use of dose-fractionation for multiple administrations of radioimmunoconjugates, exploitation of genetic engineering to construct antibody molecules with specific biological properties (i.e., altered pharmacokinetics, activation of cellular immune responses, etc.) and use of MAb-directed conjugates that can enhance tumor MAb uptake by altering tumor perfusion (7,19). The studies summarized here as well as those from other laboratories have served as the framework for clinical investigations designed to determine the effectiveness of the interferons and other differentiation-inducing agents to alter the tumor antigen phenotype in patients. In an earlier study, patients given IFN-alpha had improved tumor uptake of an antimelanoma MAb (20). Subsequently, we reported that i.p. IFN-gamma administration substantially upregulated TAG-72 and CEA on the surface of human tumor cells isolated from malignant ascites (21). A seminal investigation showed significant increase of TAG-72 and CEA levels in tumor biopsies from patients diagnosed with colorectal carcinoma and given systemic IFN-alpha (22). Those studies led to a clinical trial in which late stage breast cancer patients were administered interferon in combination with therapeutic doses of CC49. Some clinical responses were observed, however, the cytokine and MAb combination may have also enhanced marrow toxicity. Future studies will continue to evaluate the ability to enhance tumor antigen expression in the context of genetically engineered MAbs designed to minimize normal organ toxicity. C1 REGINA ELENA INST CANC RES,CLIN PATHOL LAB,ROME,ITALY. UNIV ROMA TOR VERGATA,DEPT SURG,SURG CLIN,ROME,ITALY. RP Greiner, JW (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BLDG 10,ROOM 8B07,BETHESDA,MD 20892, USA. RI Guadagni, Fiorella/J-4432-2013 OI Guadagni, Fiorella/0000-0003-3652-0457 NR 23 TC 13 Z9 13 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1996 VL 16 IS 4B BP 2129 EP 2133 PG 5 WC Oncology SC Oncology GA VA613 UT WOS:A1996VA61300001 PM 8694532 ER PT J AU Guadagni, F Roselli, M Cosimelli, M Ferroni, P Spila, A Cavaliere, F Arcuri, R Carlini, S Mariotti, S Gandolfo, GM Casciani, CU Greiner, JW Schlom, J AF Guadagni, F Roselli, M Cosimelli, M Ferroni, P Spila, A Cavaliere, F Arcuri, R Carlini, S Mariotti, S Gandolfo, GM Casciani, CU Greiner, JW Schlom, J TI TAG-72 expression and its role in the biological evaluation of human colorectal cancer SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT International Symposium on Tumor Markers - From Biology to Therapy CY OCT 13-15, 1995 CL KAPANDRITI, GREECE DE TAG-72; colorectal cancer; human ID MONOCLONAL-ANTIBODY B72.3; TUMOR-ASSOCIATED GLYCOPROTEIN-72; CARCINOEMBRYONIC ANTIGEN LEVELS; SEROUS EFFUSIONS; GASTROINTESTINAL CARCINOMA; CA-72-4 RADIOIMMUNOASSAY; RECOMBINANT INTERFERON; MONITORING PATIENTS; MAMMARY-TUMOR; COLON CANCER AB Immunohistochemical studies showed that TAG-72 is expressed in more than 80% of colorectal carcinomas, but is rarely expressed in normal epithelium and benign diseases. TAG-72 can also be found in the body fluids of patients with adenocarcinomas, and its direct measurement can be used in conjunction with immunocytochemical analysis to help in discriminating benign from malignant effusions. The evaluation of TAG-72 in serum of colorectal carcinoma patients showed a sensitivity of approximately 40%, comparable to that of the widely used CEA. TAG-72 serum levels correlate with the stage of disease, suggesting its utility in discriminating between early-stage versus late-stage colon carcinoma. Longitudinal studies demonstrated that TAG-72 serum levels may be used as a predictive marker of recurrences. Moreover, the simultaneous measurement of TAG-72 and CEA serum markers improves the monitoring of recurrent disease. Therefor, these data suggest that TAG-72 is a well suitable marker for colorectal cancer. C1 UNIV ROMA TOR VERGATA,DEPT SURG,ROME,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPT MED & PATHOL,ROME,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP Guadagni, F (reprint author), REGINA ELENA INST CANC RES,VIALE REGINA ELENA 291,I-00161 ROME,ITALY. RI Guadagni, Fiorella/J-4432-2013; Cavaliere, Francesco/J-7635-2016; OI Guadagni, Fiorella/0000-0003-3652-0457; Cavaliere, Francesco/0000-0001-6501-8648; Ferroni, Patrizia/0000-0002-9877-8712 NR 71 TC 7 Z9 8 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1996 VL 16 IS 4B BP 2141 EP 2148 PG 8 WC Oncology SC Oncology GA VA613 UT WOS:A1996VA61300003 PM 8694534 ER PT J AU Roselli, M Guadagni, F Buonomo, O Belardi, A Ferroni, P Diodati, A Anselmi, D Cipriani, C Casciani, CU Greiner, J Schlom, J AF Roselli, M Guadagni, F Buonomo, O Belardi, A Ferroni, P Diodati, A Anselmi, D Cipriani, C Casciani, CU Greiner, J Schlom, J TI Tumor markers as targets for selective diagnostic and therapeutic procedures SO ANTICANCER RESEARCH LA English DT Article DE monoclonal antibodies; radionuclides; biological response modifiers; human cancer; diagnosis; treatment ID MONOCLONAL-ANTIBODY B72.3; COLORECTAL-CANCER PATIENTS; GROWTH-FACTOR RECEPTOR; GLYCOPROTEIN TAG-72; COLON-CARCINOMA; ANTIGENIC HETEROGENEITY; RECOMBINANT INTERFERON; ENHANCED EXPRESSION; METASTATIC LESIONS; MAMMARY-CARCINOMA AB Monoclonal antibodies (MAbs) that are reactive with tumor associated antigens (TAAs) have led to many of the recent advances made in tumor immunology. At the present time, many of these MAbs have already been used in various aspects of patient management and in better understanding the biology of carcinoma cell populations. Because of their diversity, specificity and biological activity, these MAbs are potentially ideal agents for a variety of applications in malignant disorders such as, clinical diagnosis using serum assays, immunocytopathological analyses of effusions or fine-needle aspiration specimens, immunoscintigraphy, radioimmunoguided surgery and, with additional development, site directed immunotherapy. Nevertheless, their clinical application shows advantages and limitations. Optimization of their clinical use is actually under evaluation in several Institutions, including our Department. Many innovations have been developed over the last decade which may enhance their clinical efficacy. In this view, and optimal tumor targeting for diagnostic or therapeutic applications may require a better choice of radiotracer, generation of new molecules and the characterization of TAAs at the target level. C1 UNIV ROMA TOR VERGATA,DEPT SURG,ROME,ITALY. REGINA ELENA INST CANC RES,ROME,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPT MED & PATHOL,ROME,ITALY. S EUGENIO HOSP,DEPT NUCL MED,ROME,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. RI Buonomo, Oreste Claudio/J-4280-2012; Guadagni, Fiorella/J-4432-2013; OI Guadagni, Fiorella/0000-0003-3652-0457; Ferroni, Patrizia/0000-0002-9877-8712 NR 59 TC 10 Z9 10 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1996 VL 16 IS 4B BP 2187 EP 2192 PG 6 WC Oncology SC Oncology GA VA613 UT WOS:A1996VA61300010 PM 8694541 ER PT J AU Spila, A Roselli, M Cosimelli, M Ferroni, P Cavaliere, F Arcuri, R Tedesco, M Carlini, S DAlessandro, R Perri, P Casciani, CU Greiner, JW Schlom, J Guadagni, F AF Spila, A Roselli, M Cosimelli, M Ferroni, P Cavaliere, F Arcuri, R Tedesco, M Carlini, S DAlessandro, R Perri, P Casciani, CU Greiner, JW Schlom, J Guadagni, F TI Clinical utility of CA 72-4 serum marker in the staging and immediate post-surgical management of gastric cancer patients SO ANTICANCER RESEARCH LA English DT Article DE serum markers; CA 72-4; CEA; CA 19-9; gastric cancer; staging; surgical treatment; post-surgical monitoring; serum markers' half-life ID TUMOR-ASSOCIATED GLYCOPROTEIN-72; MONOCLONAL-ANTIBODY B72.3; CARCINOEMBRYONIC ANTIGEN; GASTROINTESTINAL CARCINOMA; MONITORING PATIENTS; COLORECTAL-CANCER; TAG-72; CA-19-9; COLON; ASSAY AB CA 72-4 is a high molecular weight, pancarcinoma human tumor mucin which may play an important role in the identification (i.e., staging) and clinical management of patients with gastric carcinoma. In the present study of 242 patients with primary or recurrent gastric cancer, a higher percentage of these patients have measurable serum CA 72-4 levels when compared with either CA 19.9 or CEA. Moreover, the presence of positive serum CA 72-4 levels correlated with the presence of lymph node involvement and with identification of patients with a poor prognosis due to the presence of an advanced stage of gastric cancer. Post-operative monitoring of serum CA 72-4 revealed that the disappearance of CA 72-4 often indicated curative surgery which correlated with a longer disease-free interval. Additional clinical studies are needed to better evaluate the role of CA 72-4 as a serum marker for human gastric carcinoma. Concomitant studies should also focus on what role CA 72-4 may play in the initiation and/or progression of the gastric carcinoma phenotype. C1 REGINA ELENA INST CANC RES,CLIN PATHOL LAB,I-00161 ROME,ITALY. UNIV ROMA TOR VERGATA,DEPT SURG,ROME,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPT MED & PATHOL,ROME,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RI Guadagni, Fiorella/J-4432-2013; Cavaliere, Francesco/J-7635-2016; OI Guadagni, Fiorella/0000-0003-3652-0457; Cavaliere, Francesco/0000-0001-6501-8648; Ferroni, Patrizia/0000-0002-9877-8712 NR 34 TC 23 Z9 26 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1996 VL 16 IS 4B BP 2241 EP 2247 PG 7 WC Oncology SC Oncology GA VA613 UT WOS:A1996VA61300019 PM 8694550 ER PT J AU Davey, RT Chaitt, DG Reed, GF Freimuth, WW Herpin, BR Metcalf, JA Eastman, PS Falloon, J Kovacs, JA Polis, MA Walker, RE Masur, H Boyle, J Coleman, S Cox, SR Wathen, L Daenzer, CL Lane, HC AF Davey, RT Chaitt, DG Reed, GF Freimuth, WW Herpin, BR Metcalf, JA Eastman, PS Falloon, J Kovacs, JA Polis, MA Walker, RE Masur, H Boyle, J Coleman, S Cox, SR Wathen, L Daenzer, CL Lane, HC TI Randomized, controlled phase I/II trial of combination therapy with delavirdine (U-90152S) and conventional nucleosides in human immunodeficiency virus type 1-infected patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID REVERSE-TRANSCRIPTASE; INHIBITORS; RESISTANCE; REPLICATION; PLASMA AB Delavirdine mesylate (DLV) is a potent nonnucleoside reverse transcriptase inhibitor with activity specific for human immunodeficiency virus type 1. In the present phase I/II study we evaluated the safety, toxicity, pharmacokinetics, and antiretroviral activities of two-drug and three-drug combinations of DLV and conventional doses of nucleoside analogs compared with those of both DLV monotherapy and two-drug nucleoside analog therapy, A total of 85 human immunodeficiency virus type 1 infected patients with CD4 counts of 100 to 300 cells per mm(3) were enrolled in two periods: in the first period, patients were randomized to receive either zidovudine (ZDV) plus didanosine (group 1) or ZDV plus didanosine plus escalating doses (400 to 1,200 mg/day) of DLV (group 2). In the second period, patients were randomized to receive either 1,200 mg of DLV alone per day (group 3) or ZDV plus 1,200 mg of DLV per day (group 4), DLV demonstrated good oral bioavailability at all five doses tested. The major toxicity was a transient mild rash which appeared in 44% of all DLV recipients, Overall, group 2 patients demonstrated more sustained improvements in CD4 counts, percent CD4 cells, branched DNA levels, p24 antigen levels, and virus titers in plasma than group 1, 3, or 4 patients, The magnitude of the response correlated with the intensity of prior nucleoside analog treatment, the non-syncytium-inducing or syncytium-inducing viral phenotype at baseline, and the presence of a wild-type codon at amino acid position 215 in the baseline reverse transcriptase genotype, Despite a transient rash, DLV therapy was web tolerated, Combination therapy with DW and nucleoside analogs appears promising, with the three-drug combination appearing to be more potent than either two-drug combinations or monotherapy. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. UPJOHN CO,KALAMAZOO,MI 49007. CHIRON CORP,EMERYVILLE,CA 94608. RP Davey, RT (reprint author), NIAID,NIH,BLDG 10,ROOM 11C103,BETHESDA,MD 20892, USA. OI Polis, Michael/0000-0002-9151-2268 NR 22 TC 52 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1996 VL 40 IS 7 BP 1657 EP 1664 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UW379 UT WOS:A1996UW37900016 PM 8807058 ER PT J AU Kan, VL Geber, A Bennett, JE AF Kan, VL Geber, A Bennett, JE TI Enhanced oxidative killing of azole-resistant Candida glabrata strains with ERG11 deletion SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL AGENTS; ALBICANS; FLUCONAZOLE; LEUKOCYTES; PHAGOCYTOSIS; AIDS AB The susceptibility of genetically defined Candida glabrata strains to killing by H2O2 and neutrophils was assessed. Fluconazole susceptible L5L and L5D strains demonstrated survival rates higher than those of two fluconazole-resistant strains lacking the ERG11 gene coding for 14 alpha-demethylase. Fluconazole resistance can occur by mechanisms which increase fungal susceptibility to oxidative killing by H2O2 and neutrophils. C1 NIAID,CLIN MYCOL SECT,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20037. RP Kan, VL (reprint author), VET AFFAIRS MED CTR,INFECT DIS SECT 151B,50 IRVING ST NW,WASHINGTON,DC 20422, USA. NR 24 TC 13 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1996 VL 40 IS 7 BP 1717 EP 1719 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UW379 UT WOS:A1996UW37900027 PM 8807069 ER PT J AU Unser, M AF Unser, M TI Quasi-orthogonality and quasi-projections SO APPLIED AND COMPUTATIONAL HARMONIC ANALYSIS LA English DT Article ID WAVELET APPROXIMATIONS; SAMPLING THEOREM; SMOOTH FUNCTIONS; MULTIRESOLUTION; OPERATORS; FORMULAS; FILTERS; ORDER AB Our main concern in this paper is the design of simplified filtering procedures for the quasi-optimal approximation of functions in subspaces of L(2) generated from the translates of a function phi(x). Examples of signal representations that fall into this framework are Schoenberg's polynomial splines of degree n, and the various multiresolution spaces associated with the wavelet transform. After a brief review of the relation between the order of approximation of the representation and the concept of quasi-interpolation (Strang-Fix conditions), we investigate the implication of these conditions on the various basis functions and their duals (vanishing moment and quasi-interpolation properties). We then introduce the notion of quasi-duality and show how to construct quasiorthogonal and quasi-dual basis functions that are much shorter than their exact counterparts. We also consider the corresponding quasi-orthogonal projection operator at sampling step h and derive asymptotic error formulas and bounds that are essentially the same as those associated with the exact least-squares solution. Finally, we use the idea of a perfect reproduction of polynomials of degree n to construct short kernel quasi-deconvolution filters that provide a well-behaved approximation of an oblique projection operator. RP Unser, M (reprint author), NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BLDG 13, ROOM 3N17, BETHESDA, MD 20892 USA. RI Unser, Michael/A-1550-2008 NR 33 TC 8 Z9 8 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 1063-5203 J9 APPL COMPUT HARMON A JI Appl. Comput. Harmon. Anal. PD JUL PY 1996 VL 3 IS 3 BP 201 EP 214 DI 10.1006/acha.1996.0016 PG 14 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA VA283 UT WOS:A1996VA28300001 ER PT J AU Costa, PT AF Costa, PT TI Work and personality: Use of the NEO-PI-R in industrial/organisational psychology SO APPLIED PSYCHOLOGY-AN INTERNATIONAL REVIEW-PSYCHOLOGIE APPLIQUEE-REVUE INTERNATIONALE LA English DT Article; Proceedings Paper CT 23rd International Congress of Applied Psychology CY JUL 17-22, 1994 CL MADRID, SPAIN SP Int Congress Appl Psychol ID PERSONNEL-SELECTION; JOB-PERFORMANCE; INVENTORY; METAANALYSIS; DIMENSIONS; VALIDITIES; NEEDS; MODEL; SCALE AB The Revised NEO Personality Inventory (NEO-PI-R) is a contemporary measure of 30 traits that define the five basic factors of normal personality. In both research and applied samples it has shown evidence of reliability and validity, and several studies suggest that it has utility in the prediction of job performance. The domain and facet features of the NEO-PI-R are discussed along with some issues in its use in industrial/organisational psychology. RP Costa, PT (reprint author), NIA,GERONTOL RES CTR,LAB PERSONAL & COGNIT,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712 NR 52 TC 49 Z9 53 U1 2 U2 17 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0269-994X J9 APPL PSYCHOL-INT REV JI Appl. Psychol.-Int. Rev.-Psychol. Appl.-Rev. Int. PD JUL PY 1996 VL 45 IS 3 BP 225 EP 241 PG 17 WC Psychology, Applied SC Psychology GA UZ004 UT WOS:A1996UZ00400003 ER PT J AU Abrams, H Anderson, H Anderson, J Ashford, N Baker, D Beaumont, P Bergeisen, G Bingham, E Castleman, B Catlin, M Christiani, D Commoner, B Colvin, M Cone, J Dement, J Demers, P Egilman, D Epstein, S Feo, O Fleming, L Frank, A FrentzelBeyme, R Frumin, E Frumkin, H Gassert, T Gochfeld, M Goldsmith, D Goldsmith, J Greenberg, M Hay, A Hirzy, W Hessl, S Howard, V Johanning, E Keogh, J Kern, D Kilburn, K Kipen, H LaDou, J Legator, M Lemen, R Levenstein, C Levy, B Mancuso, T Mehlman, M Melius, J Merchant, J Michaels, D Miller, C Mirer, F Montague, P Moses, M Moure, R Muller, R Murray, L Myers, J Needleman, H Orris, P Ozonoff, D Peters, J Plumlee, L Punnett, L Rall, D Reverent, B Richter, E Ringen, K Rinker, J Robbins, A Sekimpi, D Sherman, J Silbergeld, E Silberschmidt, M Silverstein, M Upton, A Quy, V Watterson, A Weeks, J Wegman, D Welch, D Welch, L Wong, R Ziem, G AF Abrams, H Anderson, H Anderson, J Ashford, N Baker, D Beaumont, P Bergeisen, G Bingham, E Castleman, B Catlin, M Christiani, D Commoner, B Colvin, M Cone, J Dement, J Demers, P Egilman, D Epstein, S Feo, O Fleming, L Frank, A FrentzelBeyme, R Frumin, E Frumkin, H Gassert, T Gochfeld, M Goldsmith, D Goldsmith, J Greenberg, M Hay, A Hirzy, W Hessl, S Howard, V Johanning, E Keogh, J Kern, D Kilburn, K Kipen, H LaDou, J Legator, M Lemen, R Levenstein, C Levy, B Mancuso, T Mehlman, M Melius, J Merchant, J Michaels, D Miller, C Mirer, F Montague, P Moses, M Moure, R Muller, R Murray, L Myers, J Needleman, H Orris, P Ozonoff, D Peters, J Plumlee, L Punnett, L Rall, D Reverent, B Richter, E Ringen, K Rinker, J Robbins, A Sekimpi, D Sherman, J Silbergeld, E Silberschmidt, M Silverstein, M Upton, A Quy, V Watterson, A Weeks, J Wegman, D Welch, D Welch, L Wong, R Ziem, G TI Untitled SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Letter C1 MIT, CAMBRIDGE, MA 02139 USA. UNIV CALIF IRVINE, CTR ENVIRONM & OCCUPAT HLTH, IRVINE, CA 92717 USA. PESTICIDES TRUST, LONDON, ENGLAND. UNIV CINCINNATI, KETTERING LABS, CINCINNATI, OH 45221 USA. WASHINGTON COMM OCCUPAT SAFETY & HLTH, WASHINGTON, DC USA. HARVARD UNIV, SCH PUBL HLTH, CAMBRIDGE, MA 02138 USA. CUNY, CTR BIOL NAT SYST, QUEENS COLL, NEW YORK, NY 10021 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. DUKE UNIV, MED CTR, DIV ENVIRONM & OCCUPAT MED, DURHAM, NC 27706 USA. UNIV BRITISH COLUMBIA, OCCUPAT HLTH PROGRAM, VANCOUVER, BC V5Z 1M9, CANADA. BROWN UNIV, DEPT COMMUNITY MED, PROVIDENCE, RI 02912 USA. UNIV ILLINOIS, CHICAGO, IL 60680 USA. UNIV MIAMI, SCH MED, DEPT EPIDEMIOL & PUBL HLTH, CORAL GABLES, FL 33124 USA. UNIV TEXAS, CTR HLTH, DEPT ENVIRONM & OCCUPAT MED, TYLER, TX 75710 USA. UNIV BREMEN, SECT ENVIRONM & OCCUPAT EPIDEMIOL, D-2800 BREMEN 33, GERMANY. EMORY UNIV, ROLLINS SCH PUBL HLTH, DEPT ENVIRONM & OCCUPAT MED, ATLANTA, GA 30322 USA. UNIV MED & DENT NEW JERSEY, ENVIRONM & OCCUPAT HLTH SCI INST, NEW BRUNSWICK, NJ USA. WESTERN CONSORTIUM PUBL HLTH, BERKELEY, CA USA. BEN GURION UNIV NEGEV, ENVIRONM & OCCUPAT MED SECT, IL-84105 BEER SHEVA, ISRAEL. UNIV LEEDS, SCH MED, DEPT PATHOL SCI, LEEDS LS2 9JT, W YORKSHIRE, ENGLAND. COOK CTY HOSP, DIV OCCUPAT MED, CHICAGO, IL 60612 USA. UNIV LIVERPOOL, SCH MED, DEPT FOETAL PATHOL, LIVERPOOL L69 3BX, MERSEYSIDE, ENGLAND. EASTERN NEW YORK OCCUPAT HLTH PROGRAM, NEW YORK, NY USA. UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. BROWN UNIV, SCH MED, PROGRAM OCCUPAT MED, PROVIDENCE, RI 02912 USA. UNIV SO CALIF, SCH MED, DIV OCCUPAT & ENVIRONM HLTH, LOS ANGELES, CA 90089 USA. UNIV MED & DENT NEW JERSEY, ROBERT WOOD JOHNSON MED SCH, ENVIRONM & OCCUPAT HLTH SCI INST, NEWARK, NJ 07103 USA. UNIV TEXAS, MED BRANCH, DIV ENVIRONM TOXICOL, GALVESTON, TX 77550 USA. UNIV MASSACHUSETTS, DEPT WORK ENVIRONM, LOWELL, MA USA. AMER PUBL HLTH ASSOC, WASHINGTON, DC USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, PITTSBURGH, PA USA. UNIV IOWA, ENVIRONM HLTH SCI RES CTR, IOWA CITY, IA 52242 USA. CUNY, SCH MED, DEPT COMMUNITY HLTH & SOCIAL MED, NEW YORK, NY 10031 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. UAW, HLTH & SAFETY DEPT, WASHINGTON, DC USA. ENVIRONM RES FDN, ANNAPOLIS, MD USA. PESTICIDE EDUC CTR, SAN FRANCISCO, CA USA. UNIV MASSACHUSETTS, DEPT WORK ENVIRONM, LOWELL, MA USA. UNIV BREMEN, CTR SOCIAL POLICY RES, BREMEN, GERMANY. UNIV CAPE TOWN, SCH MED, DEPT COMMUNITY HLTH, ZA-7700 RONDEBOSCH, SOUTH AFRICA. UNIV ILLINOIS, SCH PUBL HLTH, GREAT LAKES CTR OCCUPAT & ENVIRONM SAFETY & HLTH, CHICAGO, IL 60680 USA. BOSTON UNIV, SCH PUBL HLTH, ENVIRONM HLTH SECT, BOSTON, MA 02215 USA. US EPA, OFF RES & DEV, WASHINGTON, DC 20460 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. HEBREW UNIV JERUSALEM, HADASSAH SCH PUBL HLTH & COMMUNITY MED, UNIT OCCUPAT & ENVIRONM MED, JERUSALEM, ISRAEL. CTR PROTECT WORKERS RIGHTS, WASHINGTON, DC USA. OSHFA LTD, KAMPALA, UGANDA. WESTERN MICHIGAN UNIV, KALAMAZOO, MI 49008 USA. UNIV MARYLAND, SCH MED, ENVIRONM DEF FUND, BALTIMORE, MD 21201 USA. VIETNAM NATL UNIV, CTR NAT RESOURCES & ENVIRONM STUDIES, HANOI, VIETNAM. DE MONTFORT UNIV, CTR ENVIRONM & OCCUPAT HLTH, LEICESTER LE1 9BH, LEICS, ENGLAND. GEORGE WASHINGTON UNIV, MED CTR, DIV ENVIRONM & OCCUPAT MED, WASHINGTON, DC 20052 USA. SUNRAY OCCUPAT HLTH CLIN, TORONTO, ON, CANADA. CARL BRO INT, ENERGY WATER & ENVIRONM DIV, GLOSTRUP, DENMARK. NYU, NEW YORK, NY 10012 USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, BALTIMORE, MD USA. RP Abrams, H (reprint author), UNIV ARIZONA, DEPT COMMUNITY & FAMILY MED, TUCSON, AZ 85721 USA. NR 11 TC 7 Z9 7 U1 1 U2 3 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD JUL-AUG PY 1996 VL 51 IS 4 BP 338 EP 340 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA VC547 UT WOS:A1996VC54700014 ER PT J AU Goldman, LR Huggett, RJ Olden, K Medford, RL Rosenstock, L Johnson, BL Schultz, WB Hunker, JA AF Goldman, LR Huggett, RJ Olden, K Medford, RL Rosenstock, L Johnson, BL Schultz, WB Hunker, JA TI Untitled - Response 2 SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Letter C1 US EPA,OFF RES & DEV,WASHINGTON,DC. NIEHS,RES TRIANGLE PK,NC 27709. US FDA,ROCKVILLE,MD 20857. RP Goldman, LR (reprint author), US EPA,OFF PREVENT PESTICIDES & TOX SUBST,WASHINGTON,DC 20460, USA. RI Goldman, Lynn/D-5372-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD JUL-AUG PY 1996 VL 51 IS 4 BP 342 EP 342 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA VC547 UT WOS:A1996VC54700016 ER PT J AU Murphy, DGM DeCarli, C McIntosh, AR Daly, E Mentis, MJ Pietrini, P Szczepanik, J Schapiro, MB Grady, CL Horwitz, B Rapoport, SI AF Murphy, DGM DeCarli, C McIntosh, AR Daly, E Mentis, MJ Pietrini, P Szczepanik, J Schapiro, MB Grady, CL Horwitz, B Rapoport, SI TI Sex differences in human brain morphometry and metabolism: An in vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CEREBROVASCULAR RISK-FACTORS; HUMAN CORPUS-CALLOSUM; CEREBRAL BLOOD-FLOW; ALZHEIMERS-DISEASE; GENDER DIFFERENCES; INDIVIDUAL-DIFFERENCES; BIOLOGICAL MECHANISMS; CEREBROSPINAL-FLUID; DEMENTING ILLNESSES; MEMORY PERFORMANCE AB Background: There are significant age and sex effects in cognitive ability and brain disease. However, sex differences in aging of human brain areas associated with nonreproductive behavior have not been extensively studied. We hypothesized that there would be significant sex differences in aging of brain areas that subserve speech, visuospatial, and memory function. Methods: We investigated sex differences in the effect of aging on human brain morphometry by means of volumetric magnetic resonance imaging and on regional cerebral metabolism for glucose by positron emission tomography. In the magnetic resonance imaging study, we examined 69 healthy right-handed subjects (34 women and 35 men), divided into young (age range, 20 to 35 years) and old (60 to 85 years) groups. In the positron emission tomography study, we investigated 120 healthy right-handed subjects (65 women and 55 men) aged 21 to 91 years. Results: In the magnetic resonance imaging study, age-related volume loss was significantly greater in men than women in whole brain and frontal and temporal lobes, whereas it was greater in women than men in hippocampus and parietal lobes. In the positron emission tomography study, significant sex differences existed in the effect of age on regional brain metabolism, and asymmetry of metabolism, in the temporal and parietal lobes, Broca's area, thalamus, and hippocampus. Conclusions: We found significant sex differences in aging of brain areas that are essential to higher cognitive functioning. Thus, our findings may explain some of the age-sex differences in human cognition and response to brain injury and disease. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. RI DeCarli, Charles/B-5541-2009; McIntosh, Anthony/G-4955-2011; daly, eileen/B-6716-2011 NR 99 TC 346 Z9 351 U1 1 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1996 VL 53 IS 7 BP 585 EP 594 PG 10 WC Psychiatry SC Psychiatry GA UW182 UT WOS:A1996UW18200004 PM 8660125 ER PT J AU Castellanos, FX Giedd, JN Marsh, WL Hamburger, SD Vaituzis, AC Dickstein, DP Sarfatti, SE Vauss, YC Snell, JW Lange, N Kaysen, D Krain, AL Ritchie, GF Rajapakse, JC Rapoport, JL AF Castellanos, FX Giedd, JN Marsh, WL Hamburger, SD Vaituzis, AC Dickstein, DP Sarfatti, SE Vauss, YC Snell, JW Lange, N Kaysen, D Krain, AL Ritchie, GF Rajapakse, JC Rapoport, JL TI Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID BASAL GANGLIA; PSYCHIATRIC STATUS; LEARNING-DISABILITIES; TOURETTES-SYNDROME; CEREBRAL STRUCTURE; CORPUS-CALLOSUM; CAUDATE-NUCLEUS; SEX-DIFFERENCES; TEMPORAL-LOBE; CHILDREN AB Background: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. Method: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. Conclusion: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT NEUROSURG,CHARLOTTESVILLE,VA 22908. NINCDS,BETHESDA,MD 20892. BROWN UNIV,PROVIDENCE,RI 02912. UNIV PENN,PHILADELPHIA,PA 19104. RP Castellanos, FX (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR,MSC 1600,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Roy, Amy/J-7613-2013; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Dickstein, Daniel/L-3210-2016 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Dickstein, Daniel/0000-0003-1647-5329 NR 113 TC 727 Z9 742 U1 15 U2 48 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1996 VL 53 IS 7 BP 607 EP 616 PG 10 WC Psychiatry SC Psychiatry GA UW182 UT WOS:A1996UW18200006 PM 8660127 ER PT J AU Frazier, JA Giedd, JN Hamburger, SD Albus, KE Kaysen, D Vaituzis, AC Rajapakse, JC Lenane, MC McKenna, K Jacobsen, LK Gordon, CT Breier, A Rapoport, JL AF Frazier, JA Giedd, JN Hamburger, SD Albus, KE Kaysen, D Vaituzis, AC Rajapakse, JC Lenane, MC McKenna, K Jacobsen, LK Gordon, CT Breier, A Rapoport, JL TI Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID STRUCTURAL ABNORMALITIES; BASAL GANGLIA; 1ST-EPISODE SCHIZOPHRENIA; VENTRICULAR ENLARGEMENT; CORTEX; MORPHOLOGY; DISORDER; PHENOMENOLOGY; HALOPERIDOL; DOPAMINE AB Background: Early-onset schizophrenia (first psychotic symptoms by age 12 years) has been the subject of a small number of studies, and its biological continuity with later-onset disorder has not been established. In this study, quantitative anatomic brain magnetic resonance images of children and adolescents with early-onset schizophrenia were compared with those of matched controls. Brain abnormalities in childhood-onset schizophrenia were examined in relation to those reported for later-onset schizophrenics. Methods: Anatomic brain magnetic resonance imaging scans were obtained for 21 patients (mean+/-SD age, 14.6+/-2.1 years; range, 10 to 18 years) with childhood-onset schizophrenia (13 males, eight females) and 33 age-, sex-, height-, and weight-matched normal controls. Quantitative measurements were obtained for the cerebrum, anterior frontal region, lateral ventricles, thalamus, caudate, putamen, and globus pallidus. Results: Total cerebral volume and midsagittal thalamicarea were smaller in the patients (analysis of variance, P=.002, and analysis of covariance, P=.03, respectively); the caudate, putamen, and globus pallidus were larger in the patients (analysis of covariance, P=.05, P=.007, and P<.001, respectively); and the lateral ventricles tended to be larger in the patients (analysis of covariance, P=.06). Globus pallidus enlargement correlated with neuroleptic exposure and with age of onset of psychosis. The magnitude of abnormalities compared with controls was similar to that reported in adult studies, although there was a trend toward relatively smaller cerebral volumes for the childhood-onset group compared with controls. Conclusion: Brain anatomic abnormalities in childhood-onset schizophrenia are similar to those reported for adult populations, indicating overall continuity between these rare childhood cases and the adult schizophrenia populations. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20902. NORTHWESTERN UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,CHICAGO,IL 60611. UNIV MARYLAND,CHILD PSYCHIAT DIV,BALTIMORE,MD 21201. RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 89 TC 152 Z9 153 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 1996 VL 53 IS 7 BP 617 EP 624 PG 8 WC Psychiatry SC Psychiatry GA UW182 UT WOS:A1996UW18200007 PM 8660128 ER PT J AU Viticchi, C Piantanelli, L Rossano, F Spector, NH AF Viticchi, C Piantanelli, L Rossano, F Spector, NH TI Age-related regulation of mouse brain cortex adrenoceptors following camphor vapor exposition SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE adrenoceptor brain cortex; camphor vapor exposition; cognitive stress in aging mice ID BETA-ADRENOCEPTORS; DIFFERENTIAL REGULATION; RECEPTOR SUBTYPES; RECOVERY; MICE; OLD AB The paper deals with the ability of adrenergic receptors (AR) of mouse brain cortex to be differentially regulated in response to single or multiple expositions to camphor vapor, The regulation of alpha- and beta-adrenoceptors has been studied in young and old Balb/c-nu mice. Results confirm the decrease of total beta-adrenoceptor density previously observed in untreated mice with advancing age; in addition, receptor density decreases in both young and old mice after a single exposition to camphor vapor, followed by an adaptation after multiple stimuli. The beta(1), subtype is mainly responsible for density decrease in young animals, while both beta(1) and beta(2) subtypes contribute to the decrease in old mice. On the contrary, beta(2) subpopulation gives the major contribution to the adaptive recovery in both young and old mice. alpha-Adrenoceptors also show an age-related decrease in the control group; after a single exposition they show an increased density with the exception of alpha(1)-subset in the young group. Repeated expositions lead to a rather general adaptive response towards pre-stimuli conditions. The differential behaviour of receptor subtypes in response to camphor vapor exposition can be related to the differential alterations of receptor characteristics observed during aging and also suggests a possible mechanism through which these alterations may occur. C1 NIH,DIV FUNDAMENTAL NEUROSCI,BETHESDA,MD 20892. RP Viticchi, C (reprint author), INRCA ANCONA,DEPT GERONTOL RES,CTR BIOCHEM,VIA BIRARELLI 8,I-60121 ANCONA,ITALY. NR 20 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD JUL-AUG PY 1996 VL 23 IS 1 BP 39 EP 45 DI 10.1016/0167-4943(96)00706-6 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA UY442 UT WOS:A1996UY44200004 PM 18653101 ER PT J AU George, MS Parekh, PI Rosinsky, N Ketter, TA Kimbrell, TA Heilman, KM Herscovitch, P Post, RM AF George, MS Parekh, PI Rosinsky, N Ketter, TA Kimbrell, TA Heilman, KM Herscovitch, P Post, RM TI Understanding emotional prosody activates right hemisphere regions SO ARCHIVES OF NEUROLOGY LA English DT Article ID LANGUAGE; PET; COMPREHENSION; ORGANIZATION; APROSODIAS; ANATOMY; WORDS AB Background: Defects in expressing or understanding the affective or emotional tone of speech (aprosodias) have been associated with right hemisphere dysfunction, while defects of propositional language have been linked to left hemisphere disease. The brain regions involved in recognition of emotional prosody in healthy subjects is less clear. Objectives: To investigate the brain regions involved in understanding emotional prosody and to determine whether these differ from those involved in understanding emotion based on propositional content. Methods: We studied 13 healthy subjects using water labeled with radioactive oxygen 15 and positron emission tomography while they listened to 3 similar sets of spoken English sentences. In different tasks, their responses were based on the emotional propositional content, on the emotional intonation of the sentence (prosody), or on their ability to repeat the second word in the sentence (control). Results: Understanding propositional content activated the prefrontal cortex bilaterally, on the left more than on the right. In contrast, responding to the emotional prosody activated the right prefrontal cortex. Conclusion: Neurologically healthy subjects activate right hemisphere regions during emotional prosody recognition. C1 NIMH,BIOL PSYCHIAT BRANCH,DIV INTRAMURAL RES PROGRAMS,BETHESDA,MD 20892. NIH,PET DEPT,CTR CLIN,BETHESDA,MD. UNIV FLORIDA,DEPT NEUROL,GAINESVILLE,FL 32611. MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. RALPH H JOHNSON VET ADM MED CTR,CHARLESTON,SC. RP George, MS (reprint author), MED UNIV S CAROLINA,DEPT RADIOL,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 40 TC 175 Z9 178 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 1996 VL 53 IS 7 BP 665 EP 670 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA UW177 UT WOS:A1996UW17700013 PM 8929174 ER PT J AU Lewis, RA Clogston, P Fainstein, V Gross, R Samo, TC Tuttle, C Jabs, DA Apuzzo, L Bartlett, J Coleson, L Dunn, JP Eldred, L Feinberg, J Flynn, T King, R Leslie, J Barron, B Greenspan, D Heinemann, MD Polsky, B Squires, K WiseCampbell, S Friedman, AH Cheung, TW Justin, N Teich, S Sacks, H Severin, C Friedberg, DN Addessi, A Dieterich, D Frost, K Weinberg, D Jampol, L Murphy, R Naughton, K Henderly, D Holland, GN Chafey, S Fall, H Hardy, WD Kimbrell, C McArthurChang, L Freeman, WR Meinert, L Peterson, TJ Quiceno, JI Rickman, L Simanello, MA Spector, S ODonnell, J Hoffman, J Irvine, A Jacobson, M Larson, J Seiff, S Wanner, M Davis, J Chuang, E Espinal, M Mendez, P Vandenbroucke, R Cheesman, SH Gittinger, J Haubrich, R Kachadoorian, H Tolson, K Kline, JM Klemm, AC Stevens, M Webb, R BrownBellamy, J Markowitz, JA Brookmeyer, R Collins, KB Collison, BJ Dodge, J Donithan, M Fink, N Gilpin, AMK Gerczak, C Holbrook, JT Isaacson, MR Levine, CR Martin, B Min, YI Owens, RM Nowakowski, DJ Saah, A Singer, S Smith, M Sternberg, AL Tonascia, J VanNatta, ML Davies, MD AgresSegal, M Armstrong, J Brickbauer, J Brothers, R Freitag, G Hubbard, L Hurlburt, D Jensen, K Kastorff, L King, B Magli, Y Messing, S Miner, K Neider, M Onofrey, J Stoppenbach, V Thomas, S VanderhoofYoung, M Stewart, G Hughes, R Welch, L Kurinij, N Mowery, R Ellenberg, S Korvick, J Davis, MD Clark, T Clogston, PS Freeman, W Kolvick, J Mowery, R Sattler, F Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, J Smith, H Whitley, R Bowers, M Cheng, B Lambert, AG Link, D AF Lewis, RA Clogston, P Fainstein, V Gross, R Samo, TC Tuttle, C Jabs, DA Apuzzo, L Bartlett, J Coleson, L Dunn, JP Eldred, L Feinberg, J Flynn, T King, R Leslie, J Barron, B Greenspan, D Heinemann, MD Polsky, B Squires, K WiseCampbell, S Friedman, AH Cheung, TW Justin, N Teich, S Sacks, H Severin, C Friedberg, DN Addessi, A Dieterich, D Frost, K Weinberg, D Jampol, L Murphy, R Naughton, K Henderly, D Holland, GN Chafey, S Fall, H Hardy, WD Kimbrell, C McArthurChang, L Freeman, WR Meinert, L Peterson, TJ Quiceno, JI Rickman, L Simanello, MA Spector, S ODonnell, J Hoffman, J Irvine, A Jacobson, M Larson, J Seiff, S Wanner, M Davis, J Chuang, E Espinal, M Mendez, P Vandenbroucke, R Cheesman, SH Gittinger, J Haubrich, R Kachadoorian, H Tolson, K Kline, JM Klemm, AC Stevens, M Webb, R BrownBellamy, J Markowitz, JA Brookmeyer, R Collins, KB Collison, BJ Dodge, J Donithan, M Fink, N Gilpin, AMK Gerczak, C Holbrook, JT Isaacson, MR Levine, CR Martin, B Min, YI Owens, RM Nowakowski, DJ Saah, A Singer, S Smith, M Sternberg, AL Tonascia, J VanNatta, ML Davies, MD AgresSegal, M Armstrong, J Brickbauer, J Brothers, R Freitag, G Hubbard, L Hurlburt, D Jensen, K Kastorff, L King, B Magli, Y Messing, S Miner, K Neider, M Onofrey, J Stoppenbach, V Thomas, S VanderhoofYoung, M Stewart, G Hughes, R Welch, L Kurinij, N Mowery, R Ellenberg, S Korvick, J Davis, MD Clark, T Clogston, PS Freeman, W Kolvick, J Mowery, R Sattler, F Brown, BW Conway, B Grizzle, J Nussenblatt, R Phair, J Smith, H Whitley, R Bowers, M Cheng, B Lambert, AG Link, D TI Assessment of cytomegalovirus retinitis - Clinical evaluation vs centralized grading of fundus photographs SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Background: In the Foscarnet-Ganciclovir Cytomegalovirus (CMV) Retinitis Trial, time to first progression of newly diagnosed CMV retinitis was similar in the 2 treatment groups but was shorter when assessed by grading of fundus photographs at a central reading center than when assessed at the participating clinical centers. This report describes the extent and causes of this disagreement and considers the implications of the findings for clinical practice and future research. Methods: Clinical findings and photographic gradings were compared for extent and activity of retinitis at baseline and during follow-up. In selected cases of disagreement, the photographs and summaries of gradings and clinical findings were reviewed concurrently to determine the cause of disagreement. Results: Movement of the border of retinitis was observed sooner and activity of the border was considered to have increased more often at the reading center than at the clinical centers. Disagreements on time to first progression were more frequent when degree of border movement was small (odds ratios [ORs] for several comparisons ranged from 1.7 to 5.2), when border activity was judged to have decreased or remained the same since the preceding visit (OR, 2.0-193), and when retinitis at baseline did not involve zone 1 (the area within 1 disc diameter of the disc or within 2 disc diameters of the center of the macula [OR, 1.4-3.6]). There were 2 important causes of disagreement between clinical center and reading center. First, difficulty was encountered clinically in recognizing retinitis border movement in the absence of an obvious increase in border activity. Second, the reading center used a threshold for border movement small enough to be crossed by an initial expansion of retinitis borders occurring within 2 to 5 weeks of enrollment in some patients who were responding favorably to treatment (in that retinitis was becoming inactive and showed no further progression for many weeks). Conclusions: Comparisons of photographs from the current visit with those from several previous visits may increase clinicians' abilities to detect progression promptly. The use of additional outcome measures by reading centers, such as border movement of 1500 pm or more and change in area of retina involved by retinitis, may provide more accurate and useful comparisons of treatments. In making such comparisons, centralized photographic grading has the advantages of greater reproducibility and lesser risk of observer bias. C1 BAYLOR COLL MED,CULLEN EYE INST,HOUSTON,TX 77030. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NEW YORK HOSP,CORNELL MED CTR,NEW YORK,NY 10021. MT SINAI SCH MED,NEW YORK,NY. NYU,MED CTR,NEW YORK,NY. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. USN HOSP,BETHESDA,MD 20814. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV MIAMI,SCH MED,CORAL GABLES,FL 33124. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. UNIV WISCONSIN,FUNDUS PHOTOGRAPH READING CTR,MADISON,WI. ERC BIOSERV CORP,DRUG DISTRIBUT CTR,ROCKVILLE,MD. NIAID,BETHESDA,MD 20892. RP Lewis, RA (reprint author), JOHNS HOPKINS UNIV,SCH MED,WILMER OPHTHALMOL INST,550 N BROADWAY,SUITE 700,BALTIMORE,MD 21205, USA. NR 8 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1996 VL 114 IS 7 BP 791 EP 805 PG 15 WC Ophthalmology SC Ophthalmology GA UX515 UT WOS:A1996UX51500001 ER PT J AU Kupfer, C AF Kupfer, C TI General principles for AIDS research SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material RP Kupfer, C (reprint author), NEI,31 CTR DR,MSC 2510,BLDG 31,ROOM 6A03,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1996 VL 114 IS 7 BP 862 EP 862 PG 1 WC Ophthalmology SC Ophthalmology GA UX515 UT WOS:A1996UX51500012 PM 8660171 ER PT J AU Nagler, RM Baum, BJ Fox, PC AF Nagler, RM Baum, BJ Fox, PC TI A 2 week pair-fed study of early X-irradiation effects on rat major salivary gland function SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE salivary glands; irradiation; parotid gland; submandibular gland; pair-feeding ID ACINAR-CELLS; LIQUID-DIET; FLOW AB Salivary gland function is affected shortly after irradiation of the head and neck. An intense oral mucositis develops after exposure and may interfere with ingestion. The effects of restricted food and water intake on the secretory output of rat major salivary glands were examined. Parotid and submandibular salivary output and body weight were measured in rats at 4, 8, 11 and 14 days after 15 Gy X-irradiation of the head and neck. Comparisons were made with two groups: a non-irradiated group with food and water intake restricted to that of the irradiated group (pair-fed), and a non-irradiated, ad libitum-fed control group. Parotid saliva output was significantly decreased in the irradiated group at 4, 8 and 11 days compared with the control group. The pair-fed rats also had significantly decreased parotid output at these time points and their parotid function did not differ from that of the irradiated animals. At 14 days, all three groups demonstrated similar parotid function. Submandibular salivary output was not affected to the same extent. Only at a single time point (11 days) was flow significantly decreased in the irradiated group. Total body weight was less than that of control rats for both the irradiated and pair-fed animals at all time points. These results suggest that the early effects of radiation on salivary glands are due, in part, to limited intake of food and water during the immediate postirradiation period. Copyright (C) 1996 Published by Elsevier Science Ltd. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. NR 23 TC 19 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD JUL PY 1996 VL 41 IS 7 BP 713 EP 717 DI 10.1016/S0003-9969(96)00025-8 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WD108 UT WOS:A1996WD10800014 PM 9015574 ER PT J AU Paakko, P Anttila, S Sormunen, R AlaKokko, L Peura, R Ferrans, VJ Ryhanen, L AF Paakko, P Anttila, S Sormunen, R AlaKokko, L Peura, R Ferrans, VJ Ryhanen, L TI Biochemical and morphological characterization of carbon tetrachloride induced lung fibrosis in rats SO ARCHIVES OF TOXICOLOGY LA English DT Article DE carbon tetrachloride; lung injury; collagens; crystals ID INDUCED PULMONARY FIBROSIS; PROLYL HYDROXYLASE; COLLAGEN-GALACTOSYLTRANSFERASE; BASEMENT-MEMBRANES; HEPATIC INJURY; CLARA CELL; LIVER; ACCUMULATION; LAMININ; GLUCOSYLTRANSFERASE AB The short-term and long-term lung CCl4 injuries in rats were studied by i.p. CCl4 for 2 or 5 weeks, respectively, and the lung injury in the third progression group receiving i.p. CCl4 for 2 weeks followed by 3 weeks without. Acute haemorrhagic interstitial pneumonia resulted from short-term injury; chronic interstitial pneumonia from long term injury, and residua of injury or advanced chronic interstitial pneumonia in the progression group. All groups also exhibited features for diffuse alveolar damage. Connective tissue stains revealed both interstitial and intra-alveolar fibrosis in short-term injury. Hydroxyproline content and the activities of prolyl hydroxylase and galactosyl-hydroxylysyl glucosultransferase were elevated. This suggests an early onset of pulmonary fibrosis. Immunohistochemistry revealed the interstitial accumulation of BM proteins. In contrast, increased type III pN-collagen could also be found in the intra-alveolar spaces. The degrees of both interstitial and intraalveolar fibrosis, BM proteins and type III pN-collagen, and also hydroxyproline content were greater in long-term injury, while the progression group showed on average fewer fibrotic changes than did the long-term injury group, but more than the shortterm injury pointing to persistence or progression of the changes. Additionally, intra-alveolar crystallized haemoglobin was found following short-term injury. We conclude that CCl4-induced lung injury is an useful experimental model to study pulmonary fibrosis. The mechanism of CCl4 lung injury is not known but free radical-mediated lipid peroxidation is suggested. C1 UNIV OULU,DEPT INTERNAL MED,FIN-90220 OULU,FINLAND. UNIV OULU,DEPT BIOCHEM MED,FIN-90220 OULU,FINLAND. UNIV OULU,COLLAGEN RES UNIT,FIN-90220 OULU,FINLAND. UNIV OULU,BIOCTR,FIN-90220 OULU,FINLAND. UNIV OULU,INST ELECTRON OPT,FIN-90220 OULU,FINLAND. INST OCCUPAT HLTH,HELSINKI,FINLAND. NHLBI,ULTRASTRUCT SECT,PATHOL BRANCH,NIH,BETHESDA,MD 20892. RP Paakko, P (reprint author), UNIV OULU,DEPT PATHOL,KAJAANINTIE 52,FIN-90220 OULU,FINLAND. NR 42 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD JUL PY 1996 VL 70 IS 9 BP 540 EP 552 DI 10.1007/s002040050311 PG 13 WC Toxicology SC Toxicology GA UV879 UT WOS:A1996UV87900002 PM 8831904 ER PT J AU Langford, CA Sneller, MC AF Langford, CA Sneller, MC TI Finding a valid model for human Wegener's granulomatosis: Comment SO ARTHRITIS AND RHEUMATISM LA English DT Letter RP Langford, CA (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1996 VL 39 IS 7 BP 1262 EP 1262 DI 10.1002/art.1780390732 PG 1 WC Rheumatology SC Rheumatology GA UX384 UT WOS:A1996UX38400031 PM 8670343 ER PT J AU Park, JW BlanchetteMackie, EJ Scow, RO AF Park, JW BlanchetteMackie, EJ Scow, RO TI Brefeldin A enables synthesis of active lipoprotein lipase in cld/cld and castanospermine-treated mouse brown adipocytes via translocation of Golgi components to endoplasmic reticulum SO BIOCHEMICAL JOURNAL LA English DT Article ID MURINE ERYTHROLEUKEMIA-CELLS; N-LINKED OLIGOSACCHARIDES; ALPHA-D-MANNOSIDASE; DEFICIENCY CLD; INTRACELLULAR-TRANSPORT; ADIPOSE-CELLS; NEWBORN MICE; BOVINE-MILK; SECRETION; PROTEINS AB Brown adipocytes cultured from newborn combined-lipase-deficient (cld/cld) mice and castanospermine (CST)-treated 3T3-L1 adipocytes synthesize lipoprotein lipase (LPL) which is inactive and retained in the endoplasmic reticulum (ER) [Masuno, Blanchette-Mackie, Chernick and Scow (1990) J. Biol. Chem. 265, 1628-1638; Masuno, Blanchette-Mackie, Schultz, Spaeth, Scow and Okuda (1992) J. Lipid Res. 33, 1343-1349]. Brefeldin A (BFA), which is known to block protein transport from ER and translocate Golgi components to ER, was used here to study the effect of translocated Golgi enzymes on LPL retained in ER of cld/cld and CST-treated mouse brown adipocytes. Brown adipocytes cultured from newborn normal mice contained 3000-5000 m-units of LPL activity/mg of DNA and secreted 35 m-units of LPL activity/mg of DNA per h. BFA at 10 mu g/ml doubled LPL activity in normal cells within 2 h as it stopped completely secretion of active LPL. LPL in mouse cells has two N-oligosaccharide chains per subunit. Analyses with SDS/PAGE and immunoblotting showed that about one-third of LPL subunits in untreated normal cells were totally endo-beta-N-acetylglucosaminidase (endo H)-resistant, one-third were partially endo H-resistant, and one-third were totally endo H-sensitive, BFA decreased to zero the proportion of subunits which were totally endo H-resistant, while it increased the proportion which were partially endo H-resistant. Thus, BFA blocked processing of one oligosaccharide chain per subunit to endo H-resistance. Sucrose-gradient centrifugation studies showed that BFA increased the proportion of LPL subunits in normal cells which were present as active dimers. LPL activity in cld/cld adipocytes was 120 m-units/mg of DNA and that in normal adipocytes treated with CST was 430 m-units/mg of DNA. Most LPL subunits in such cells were totally endo H-sensitive and some were partially endo H-resistant, but none were totally endo H-resistant. Some of the subunits, in both cld/cld and CST-treated cells, were present as inactive LPL dimers, BFA increased LPL activity in cld/cld cells to 2100 m-units/mg of DNA and that in CST-treated cells to 2600 m-units/mg of DNA within 2 h. BFA increased in both groups the proportion of LPL subunits which were partially endo H-resistant. BFA also increased the proportion which were present as active dimers. Immunofluorescence studies in normal and cld/cld adipocytes showed that BFA caused retention of LPL in large tubular and spherical structures and in ER, but not in Golgi. When BFA was withdrawn and protein synthesis was blocked with cycloheximide, LPL in normal cells was transferred to Golgi within 30 min and disappeared within 60 min, whereas LPL in cld/cld cells was retained in large vesicles and ER. The findings indicate that BFA enabled synthesis of active LPL in cld/cld and CST-treated cells via translocation of Golgi components to ER. Also, cld/cld cells synthesized LPL which could be processed to active lipase and the enzymes needed for activation of the lipase were present in Golgi of such cells. Production of inactive LPL in cld/cld adipocytes probably results from their inability to transport LPL from ER to Golgi. C1 NIDDKD,NIH,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NR 66 TC 20 Z9 20 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 1996 VL 317 BP 125 EP 134 PN 1 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UX077 UT WOS:A1996UX07700019 PM 8694753 ER PT J AU Zorov, DB AF Zorov, DB TI Mitochondrial transport of nucleic acids. Involvement of the benzodiazepine receptor SO BIOCHEMISTRY-MOSCOW LA English DT Article DE mitochondria; nucleic acid transport; peripheral benzodiazepine receptor; ion channels; permeability transition pore; apoptosis; mitochondria diseases; mtDNA; aging; cellular proliferation ID ADENINE-NUCLEOTIDE TRANSLOCASE; RAT-HEART MITOCHONDRIA; CYCLOSPORINE-A; CYCLOPHILIN-B; IN-VITRO; INTERMITOCHONDRIAL JUNCTIONS; MEMBRANE CHANNELS; DRUG-RESISTANCE; OUTER-MEMBRANE; TRANSFER-RNA AB A hypothesis concerning the transfer of nucleic acids across the mitochondrial membrane is proposed. According to the hypothesis, mitochondria can exchange their nucleic acids by two mechanisms: through intermitochondrial fusion and fission, and through actual transmembrane transport. In the latter case an exclusive role is played by the mitochondrial benzodiazepine receptor (MBR)(3) and components regulating the activity of its participants (adenine nucleotide translocator and mitochondrial porin). The possible transport of nucleic acids through the Ca2+-dependent permeability transition pore, apparently representing one of the functional states of mitochondrial benzodiazepine receptor, is suggested. Such mechanisms could underlie both intermitochondrial and nuclear-mitochondrial genomic exchange. A number of problems such as cellular aging, proliferation, mitochondrial diseases, multidrug resistance, intracellular traffic, and mitochondrial inheritance are discussed in light of the importance of the mitochondrial benzodiazepine receptor. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP Zorov, DB (reprint author), MOSCOW MV LOMONOSOV STATE UNIV,BELOZERSKY INST PHYSICOCHIM BIOL,MOSCOW 119899,RUSSIA. NR 86 TC 6 Z9 8 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU 233 SPRING ST, NEW YORK, NY 10013 SN 0006-2979 J9 BIOCHEMISTRY-MOSCOW+ JI Biochem.-Moscow PD JUL PY 1996 VL 61 IS 7 BP 939 EP 946 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VE129 UT WOS:A1996VE12900019 ER PT J AU Weingartner, HJ Andreason, PJ Hommer, DW Sirocco, KY Rio, DE Ruttimann, UE Rawlings, RR Eckardt, MJ AF Weingartner, HJ Andreason, PJ Hommer, DW Sirocco, KY Rio, DE Ruttimann, UE Rawlings, RR Eckardt, MJ TI Monitoring the source of memory in detoxified alcoholics SO BIOLOGICAL PSYCHIATRY LA English DT Article DE reflective cognitive operations; explicit memory; source monitoring; alcoholism; positron emission tomography (PET) ID CEREBRAL GLUCOSE-METABOLISM; FRONTAL-CORTEX; IMPAIRMENTS; DEPRESSION; ACTIVATION; ATTENTION; DISORDER; IMPLICIT AB The ability, to monitor the source of remembered information and related reflective cognitive processes was examined in normal volunteers and detoxified alcoholics. Normal volunteers were very accurate judges of whether remembered events were presented as stimuli or were self-generated, even when memory was tested 2 days later. In contrast, a subgroup of otherwise cognitively unimpaired alcoholics demonstrated impairments in the ability to track the source of remembered knowledge and were also less able to inhibit intrusion errors in recalling information from memory. These findings provide preliminary evidence of art impairment in cognitive control functions in certain alcoholics. This conclusion is supported by associated findings indicating that, among alcoholics, performance on explicit memory tasks that required reflective cognitive operations were positively correlated with glucose utilization rates in left prefrontal, temporal, and posterior orbital frontal cortical regions. C1 NIAAA,CLIN STUDIES LAB,SECT BRAIN ELECTROPHYSIOL & IMAGING,BETHESDA,MD 20892. RP Weingartner, HJ (reprint author), NIAAA,CLIN STUDIES LAB,COGNIT NEUROSCI SECT,ROOM 3B19,10 CTR DR MSC-1250,BETHESDA,MD 20892, USA. NR 47 TC 24 Z9 26 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 1996 VL 40 IS 1 BP 43 EP 53 DI 10.1016/0006-3223(95)00290-1 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UQ178 UT WOS:A1996UQ17800007 PM 8780854 ER PT J AU Chaffin, CL Peterson, RE Hutz, RJ AF Chaffin, CL Peterson, RE Hutz, RJ TI In utero and lactational exposure of female Holtzman rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin: Modulation of the estrogen signal SO BIOLOGY OF REPRODUCTION LA English DT Article ID LUTEINIZING-HORMONE SECRETION; TISSUE-SPECIFIC REGULATION; BREAST-CANCER-CELLS; AH-RECEPTOR; IN-UTERO; ANDROGENIC STATUS; MCF-7 CELLS; TCDD; PITUITARY; TOXICITY AB The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) induces severe reproductive defects in male rats when exposure occurs in utero and during lactation. Yet there is currently a paucity of information regarding the effects of this exposure paradigm in females. In the current study, we examine the effects of TCDD during fetal and perinatal development on the estrogen-signaling system in peripubertal female rats. Pregnant Holtzman rats were given 1 mu g/kg TCDD or vehicle control by gavage on gestational Day 15. Body weights were reduced, though not significantly, on postnatal Day 27. While ovarian and uterine wet weights were not increased by TCDD exposure, the percentage of body weight attributed to the ovary was increased significantly. Through use of ribonuclease protection and gel-shift assays, exposed females were compared with nonexposed counterparts for estrogen receptor (ER) mRNA and DNA-binding activity in the following tissues: hypothalamus, pituitary (mRNA only), uterus, and ovary. ER mRNA levels increased in the hypothalamus, uterus, and ovary, and decreased in the pituitary. The results of the DNA-binding assays paralleled the mRNA results in the uterus, while DNA-binding activity was decreased in the hypothalamus and was unchanged in ovarian protein extracts. Circulating concentrations of estrogen were significantly lower in TCDD-exposed rats than in controls. These data suggest that the decrease in serum estrogen may be a cause of the alterations in ER mRNA; the changes in ER DNA-binding activity may indicate alterations in either translation or posttranslational receptor processing. Overall, this study shows that TCDD may act systemically in this model, and these effects should not necessarily be characterized as antiestrogenic. C1 UNIV WISCONSIN,NIEHS,BIOMED SCI CTR,DIV BIOL SCI,MILWAUKEE,WI 53211. UNIV WISCONSIN,SCH PHARM,CTR ENVIRONM TOXICOL,MADISON,WI 53706. FU NIEHS NIH HHS [ES04184, ES06807, ES01332] NR 49 TC 85 Z9 87 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 1996 VL 55 IS 1 BP 62 EP 67 DI 10.1095/biolreprod55.1.62 PG 6 WC Reproductive Biology SC Reproductive Biology GA VE873 UT WOS:A1996VE87300010 PM 8793059 ER PT J AU Caporaso, N AF Caporaso, N TI Genetic susceptibility and the common cancers SO BIOMARKERS LA English DT Editorial Material DE genetic susceptibility; cancer; gene-environment relationship; molecular epidemiology; genetics ID LUNG-CANCER; MENDELIAN INHERITANCE; CIGARETTE-SMOKING; MUTATION; PHENOTYPE; RISK RP Caporaso, N (reprint author), NCI,GENET EPIDEMIOL BRANCH,NIH,EPN 439,6130 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 25 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 1354-750X J9 BIOMARKERS JI Biomarkers PD JUL-SEP PY 1996 VL 1 IS 3 BP 174 EP 177 DI 10.3109/13547509609079353 PG 4 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA VV687 UT WOS:A1996VV68700002 PM 23902321 ER PT J AU Mathews, JM Raymer, JH Velez, GR Garner, CE Bucher, JR AF Mathews, JM Raymer, JH Velez, GR Garner, CE Bucher, JR TI The influence of cytochrome P450 enzyme activity on the composition and quantity of volatile organics in expired breath SO BIOMARKERS LA English DT Article DE cytochrome P450; breath; volatile organic compounds ID LIPID-PEROXIDATION; RATS; 1-AMINOBENZOTRIAZOLE; INACTIVATION; COLLECTION; PENTANE; SYSTEM; P-450 AB We have previously described a method to capture, identify and quantify volatile components in expired breath. The purpose of this research is to provide a non-invasive means to measure biomarkers of metabolism in vivo. In the present studies, the effect of 1-aminobenzotriazole (ABT), an inhibitor of diverse cytochrome P450 (P450) enzymes, on the composition of volatile organic chemicals (VOCs) expired in the breath of male F-344 rats was determined in parallel with the catalytic activities and total content of hepatic P450. Intraperitoneal administration of ABT (100 mg kg(-1)) to rats resulted in markedly diminished hepatic microsomal P450 content and activities. The extent of inhibition was near maximal at 4 h, at which time approximately 50% of the total P450 content, about 65% of the CYP1A2 activity, 55% of the CYP2E1 activity and about 80% of CYP2B activity were lost. inhibition was maintained to 48 h post-dosing, but P450 content and activities had largely been restored by day 7. Concomitant with the inhibition of P450 were corresponding increases (up to several hundred-fold) in the molar amount of volatiles appearing in the breath of ABT-treated animals, and the rebound of P450 levels was attended by corresponding decreases in the appearance of breath volatiles. These studies indicate that P450 plays a major role in the metabolism of VOCs appearing in breath, and that these chemicals can serve as markers on P450 activity in vivo. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Mathews, JM (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 14 Z9 15 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 1354-750X J9 BIOMARKERS JI Biomarkers PD JUL-SEP PY 1996 VL 1 IS 3 BP 196 EP 201 DI 10.3109/13547509609079357 PG 6 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA VV687 UT WOS:A1996VV68700006 PM 23902325 ER PT J AU Separovic, F Gawrisch, K AF Separovic, F Gawrisch, K TI Effect of unsaturation on the chain order of phosphatidylcholines in a dioleoylphosphatidylethanolamine matrix SO BIOPHYSICAL JOURNAL LA English DT Article ID HEXAGONAL-HII PHASE; NUCLEAR MAGNETIC-RESONANCE; L-ALPHA; PHOSPHOLIPID BILAYER; ORIENTATIONAL ORDER; HYDROCARBON CHAINS; LIPID POLYMORPHISM; DYNAMIC STRUCTURE; PHOSPHATIDYLETHANOLAMINE; NMR AB The properties of phosphatidylcholines (PCs) having a perdeuterated stearic acid, 18:0(d35) in the sn-1 position and the fatty acid 18:0, 18:1 omega 9, 18:2 omega 6, 18:3 omega 3, 20:4 omega 6, 20:5 omega 3, or 22:6 omega 3 at the sn-2 position were investigated in a matrix of dioleoylphosphatidylethanolamine (DOPE) by H-2 and P-31 NMR spectroscopy. At a mole ratio of DOPE/PC= 5:1, the lipids form liquid crystalline lamellar phases below 40 degrees C and coexisting lamellar, inverse hexagonal (H-II), and cubic phases at higher temperatures. The sn-1 chain of the PCs in a DOPE matrix is appreciably more ordered than in pure PCs, corresponding to an increase in the hydrophobic bilayer thickness of approximately 1 Angstrom Distearoylphosphatidylcholine in the DOPE matrix has a higher sn-1 chain order than the unsaturated PCs. We observed distinct differences in the lipid order of upper and lower sections of the hydrocarbon chains caused by changes of temperature, unsaturation, headgroups, and ethanol. Unsaturation lowers chain order, mostly in the lower third of the hydrocarbon chains. By contrast, the increase in chain order caused by the DOPE matrix and the decrease in order with increasing temperature have a constant magnitude for the upper two-thirds of the chain and are smaller for the lower third. Addition of 2 M ethanol reduced order parameters, in effect reversing the increase in chain order caused by the DOPE matrix. C1 NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,NIH,ROCKVILLE,MD 20852. RI Separovic, Frances/D-9698-2011 OI Separovic, Frances/0000-0002-6484-2763 NR 49 TC 50 Z9 50 U1 0 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1996 VL 71 IS 1 BP 274 EP 282 PG 9 WC Biophysics SC Biophysics GA UV908 UT WOS:A1996UV90800030 PM 8804610 ER PT J AU Bonham, MJ Danielpour, D AF Bonham, MJ Danielpour, D TI Improved purification and yields of RNA by RNeasy(R) SO BIOTECHNIQUES LA English DT Article ID PHENOL-CHLOROFORM EXTRACTION; SINGLE-STEP METHOD; GUANIDINIUM C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 4 TC 36 Z9 37 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 1996 VL 21 IS 1 BP 57 EP & PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UV793 UT WOS:A1996UV79300012 PM 8816236 ER PT J AU Apel, WS AF Apel, WS TI Gel-Pro analyzer SO BIOTECHNOLOGY SOFTWARE & INTERNET JOURNAL LA English DT Software Review C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1088-4270 J9 BIOTECHNOL SOFTW I J JI Biotechnol. Softw. Internet J. PD JUL-AUG PY 1996 VL 13 IS 4 BP 33 EP 37 PG 5 WC Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications SC Biotechnology & Applied Microbiology; Computer Science GA WL078 UT WOS:A1996WL07800007 ER PT J AU Sitnicka, E Ruscetti, FW Priestley, GV Wolf, NS Bartelmez, SH AF Sitnicka, E Ruscetti, FW Priestley, GV Wolf, NS Bartelmez, SH TI Transforming growth factor beta(1) directly and reversibly inhibits the initial cell divisions of long-term repopulating hematopoietic stem cells SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN MARROW CULTURES; TGF-BETA; CYTOKINE PRODUCTION; STROMAL CELLS; CYCLE STATUS; FACTOR-BETA-1; MOUSE; PROLIFERATION; MECHANISMS AB Hematopoiesis appears to be regulated, in part, by a balance between extracellular positive and negative growth signals, Transforming growth factor beta-1 (TGF-beta(1)) has been shown to be a negative regulator of primitive hematopoietic cells. This study examined the direct effect of TGF-beta(1) on the proliferation and differentiation of long-term repopulating hematopoietic stem cells (LTR-HSC) in vitro, We previously reported a cell fractionation approach that includes the selection of low Hoescht 33342/low Rhodamine 123 (low Ho/Rh) cell fractions that are highly enriched for long-term repopulating cells (LTR-HSC) and also clone to a very high efficiency in the presence of stem cell factor (SCF) + interleukin-3 (IL-3) + IL-6: 90% to 100% of individually cultured low Ho/Rh cells formed high proliferative potential clones, This high cloning efficiency of an LTR-HSC enriched cell population enabled proliferation inhibition studies to be more easily interpreted. In this report, we show that the continuous presence of TGF-beta(1) directly inhibits the cell division of essentially all low Ho/Rh cells (in a dose-dependent manner) during their 0 to 5th cell division in vitro. Therefore, it follows that TGF-beta(1) must directly inhibit the proliferation of LTR-HSC contained within these low Ho/Rh cells, The time required for some low Ho/Rh cells to undergo their first cell division in vitro was also prolonged in the presence of TGF-beta(1) Furthermore, when low Ho/Rh cells were exposed to TGF-beta(1) for varying lengths of time before neutralization of the TGF-beta(1) by monoclonal antibody, the ability to form macroclones was markedly decreased after similar to 4 days of TGF-beta(1) exposure, In addition, 1 to 10 ng/mL of TGF-beta(1) resulted in a maintenance of high proliferative potential-colony-forming cell (HPP-CFC) during 8 days of culture compared with loss of HPP-CFC in cultures with no added TGF-beta(1). In conclusion, this study shows that TGF-beta(1) directly inhibits the initial stages of proliferation of LTR-HSC and appears to slow the differentiation of daughter cells of low Ho/Rh cells. (C) 1996 by The American Society of Hematology. C1 UNIV WASHINGTON,SCH MED,DEPT PATHOL,SEATTLE,WA 98195. NATL CANC INST,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LAB LEUKOCYTE BIOL,FREDERICK,MD. FU NIA NIH HHS [AG 01751]; NIDDK NIH HHS [DK 48708-02] NR 44 TC 135 Z9 138 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 82 EP 88 PG 7 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700008 PM 8704205 ER PT J AU Bodine, DM Seidel, NE Orlic, D AF Bodine, DM Seidel, NE Orlic, D TI Bone marrow collected 14 days after in vivo administration of granulocyte colony-stimulating factor and stem cell factor to mice has 10-fold more repopulating ability than untreated bone marrow SO BLOOD LA English DT Article ID IN-VIVO; HEMATOPOIETIC-CELLS; PROGENITOR CELLS; BLOOD; TRANSPLANTATION; MOUSE; PURIFICATION; NUMBER; INVIVO; LIGAND AB We have examined the repopulating ability of bone marrow and peripheral blood cells collected immediately and at intervals after treatment of donor mice with the combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF). Using a competitive repopulation assay we showed that the repopulating ability of peripheral blood cells was highest immediately after cytokine treatment and declined to normal levels within 6 weeks of the termination of treatment with G-CSF and SCF. In contrast the repopulating ability of bone marrow cells was low immediately after cytokine treatment and increased to levels that were 10-fold or more greater than marrow from untreated mice by 14 days after termination of treatment with G-CSF and SCF. This high level of repopulating activity declined to normal levels by 6 weeks after termination of treatment with G-CSF and SCF. The high level of repopulating ability was confirmed by injecting cells from G-CSF- and SCF-treated donors into unconditioned recipients. Peripheral blood cells collected immediately after treatment with G-CSF and SCF engrafted into unconditioned mice sevenfold better than an equivalent number of bone marrow cells from untreated mice. Likewise, bone marrow cells collected 14 days after treatment of the donor animal with G-CSF and SCF engrafted at 10-fold higher levels than an equivalent number of bone marrow cells from untreated mice. We conclude that the treatment of donor mice with G-CSF and SCF causes a transient increase in the repopulating ability of peripheral blood and later of bone marrow. These observations may have applications to clinical hematopoietic stem cell transplantation. RP Bodine, DM (reprint author), NATL CTR HUMAN GENOME RES,LAB GENE TRANSFER,HEMATOPOIESIS SECT,49 CONVENT DR,ROOM 3A14,MSC-4470,BETHESDA,MD 20892, USA. NR 44 TC 105 Z9 107 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 89 EP 97 PG 9 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700009 PM 8704206 ER PT J AU Kaushal, S LaRussa, VF Gartner, S Kessler, S Perfetto, S Yu, Z Ritchey, DW Xu, J Perera, P Kim, J Reid, T Mayers, DL StLouis, D Mosca, JD AF Kaushal, S LaRussa, VF Gartner, S Kessler, S Perfetto, S Yu, Z Ritchey, DW Xu, J Perera, P Kim, J Reid, T Mayers, DL StLouis, D Mosca, JD TI Exposure of human CD34(+) cells to human immunodeficiency virus type 1 does not influence their expansion and proliferation of hematopoietic progenitors in vitro SO BLOOD LA English DT Article ID HUMAN-BONE-MARROW; IMMUNE-DEFICIENCY SYNDROME; PERIPHERAL-BLOOD; INVITRO GROWTH; STEM-CELLS; INFECTION; REPLICATION; HIV-1; ABNORMALITIES; INDIVIDUALS AB The susceptibility of highly purified human CD34(+) cells to monocytotropic (Ba-L) and lymphotropic (AO18-post) strains of human immunodeficiency virus-1 (HIV-1) was examined. Liquid cultures initiated with fresh immunomagnetically purified CD34(+) cells using the K6.1 CD34 monoclonal antibody (MoAb) (K6.1/CD34(+)) were positive for HIV expression 2 weeks after exposure to HIV-1 Ba-L. These cells were initially greater than 90% CD34(+) and had undetectable monocyte contamination by flow-cytometric staining and side-scatter analyses, respectively, and undetectable T-cell contamination by CD3 polymerase chain reaction (PCR) analysis. However, secondary CD34(+) liquid cultures reselected from the primary liquid cultures 24 hours after HIV exposure by panning with the ICH3 CD34 MoAb (ICH3/CD34(+)) and maintained for an additional 14 days were negative for HIV expression. The ICH3-unbound cells were positive for both spliced and unspliced HIV RNA when exposed to HIV-1 Ba-L, and were DNA PCR positive when exposed to either monocytotropic or lymphotropic HIV-1. To further test that CD34(+) cells were not infectible by HIV-1, we exposed K6.1/CD34(+) cells continuously to HIV-1 in a culture system capable of maintaining and expanding primitive CD34(+) cells. HIV-exposed K6.1/CD34(+) cells proliferated and expanded as efficiently as uninfected cultures. However, when reselected magnetically using the K6.1 CD34 MoAb after expansion for 7 days, bound K6.1/CD34(+) cells were again negative for HIV-1 expression, whereas unbound cells were positive for HIV-1 expression. These findings suggest that a sequential CD34(+) cell-selection process, in which the two selections are separated by a brief culture period, can yield a population of CD34(+) cells that are not infected with HIV-1. This process may be useful in the design of stem or progenitor cell-based transplantation therapies for HIV infection. (C) 1996 by The American Society of Hematology. C1 WALTER REED ARMY INST RES,HENRY M JACKSON FDN ADV MIL MED,WASHINGTON,DC. WALTER REED ARMY INST RES,DEPT HEMATOL & VASC BIOL,WASHINGTON,DC. MIL MED CONSORTIUM APPL RETROVIRAL RES,ROCKVILLE,MD. NIAID,NATL INST HLTH,BETHESDA,MD 20892. NR 35 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 130 EP 137 PG 8 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700014 PM 8704167 ER PT J AU Kingma, DW Weiss, WB Jaffe, ES Kumar, S Frekko, K Raffeld, M AF Kingma, DW Weiss, WB Jaffe, ES Kumar, S Frekko, K Raffeld, M TI Epstein-Barr virus latent membrane protein-1 oncogene deletions: Correlations with malignancy in Epstein-Barr virus-associated lymphoproliferative disorders and malignant lymphomas SO BLOOD LA English DT Article ID POLYMERASE CHAIN-REACTION; NASOPHARYNGEAL CARCINOMA; HODGKINS-DISEASE; INSITU HYBRIDIZATION; GENE-EXPRESSION; CELL PHENOTYPE; VIRAL LATENCY; TRANSFORMATION; DISTINCT; LYMPHOCYTES AB LMP-1, an Epstein-Barr viral (EBV) latency protein, is considered a viral oncogene because of its ability to transform rodent fibroblasts in vivo and render them tumorigenic in nude mice. In human B cells, EBV LMP-1 induces DNA synthesis and abrogates apoptosis. LMP-1 is expressed in EBV-transformed lymphoblastoid cell lines, nasopharyngeal carcinoma (NPC), a subset of Hodgkin's disease (HD), and in EBV-associated lymphoproliferative disorders (EBV-LPDs). Recently, focused deletions near the 3' end of the LMP-1 gene (del-LMP-1, amino acids 346-355), in a region functionally related to the half-life to the LMP-1 protein, have been reported frequently in human immunodeficiency virus (HIV)-associated HD (100%) and EBV(+) Malaysian and Danish peripheral T-cell lymphomas (100%, 61% respectively), but less frequently in cases of HD not associated with HIV (28%, 33%) and infectious mononucleosis (33%). To further investigate the potential relationship of del-LMP-1 to EBV-LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases). The presence of EBV within lymphoid cells was confirmed by EBV EBER1 RNA in situ hybridization or by polymerase chain reaction (PCR) analysis. EBV strain type and LMP-1 deletion status were determined by PCR. EBV strain types segregated into two distinct distributions: HIV+ (9 A; 11 B) and non-HIV (19 A, 0 B), consistent with previous reports. Overall, del-LMP-1 were found in 1 of 5 (20%) Burkitt lymphomas (BL); 17 of 24 (71%) aggressive non-Hodgkin's lymphoma (agg-NHL), and 2 of 10 (20%) reactive lymphoid proliferations. Of the agg-NHLs, del-LMP-1 were present in 4 of 4 PT-NIL (100%); 10 of 15 HIV+ ML (67%); and 3 of 5 nonimmunodeficiency malignant lymphoma (ML, 60%). A total of 2 of 7 (28%) sporadic EBV-associated lymphoid hyperplasias contained a del-LMP-1. All del-LMP-1 were identical by DNA sequence analysis. No correlation was identified between the presence of del-LMP-l and the EBV strain type observed. The high incidence of del-LMP-l observed in agg-NHLs (71%), in contrast to the relatively low incidence observed in reactive lymphoid proliferations (28%), suggests that the deleted form may be preferentially selected in lymphomatous processes. All posttransplant agg-NHLs contained a del-LMP-1, and a similar frequency of del-LMP-1 was observed in both HIV-associated ML (66%) and nonimmunodeficiency ML (60%), suggesting that impairment of immune function alone is not a requirement for the expansion of malignant cells infected by EBV stains containing the deleted LMP-1 gene. C1 UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77550. RP Kingma, DW (reprint author), NCI,NIH,HEMATOPATHOL SECT,LAB PATHOL,DIV CANC BIOL DIAG & CTR,BLDG 10,ROOM 2N110,BETHESDA,MD 20892, USA. NR 45 TC 115 Z9 121 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 242 EP 251 PG 10 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700027 PM 8704180 ER PT J AU Bessudo, A Cherepakhin, V Johnson, TA Rassenti, LZ Feigal, E Kipps, TJ AF Bessudo, A Cherepakhin, V Johnson, TA Rassenti, LZ Feigal, E Kipps, TJ TI Favored use of immunoglobulin V(H)4 genes in AIDS-associated B-cell lymphoma SO BLOOD LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VARIABLE REGION GENES; CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN MONOCLONAL-ANTIBODIES; EXTENSIVE SOMATIC MUTATION; NON-HODGKINS-LYMPHOMA; HEAVY-CHAIN; HOMOSEXUAL MEN; MOLECULAR CHARACTERIZATION; PREFERENTIAL UTILIZATION AB We examined the lg heavy chain variable region genes (lg V-H genes) expressed in biopsy specimens of 10 patients with acquired immunodeficiency syndrome (AIDS)-associated lymphoma, Eight expressed lg V-H genes of the V(H)4 group, indicating a bias toward expression of lg V-H genes of this subgroup. Sequence analyses of lg V-H genes isolated from any one lymphoma did not reveal evidence for intraclonal diversity. However, some lymphomas express lg V-H genes that apparently have undergone somatic diversification and selection. In addition, we found that the sequence encoding each examined third complementarity determining region most likely resulted from D-D fusion, a process that ordinarily contributes to the generation of a relatively small proportion of the lg heavy chain genes expressed by normal adult B cells. The noted restriction in the use of lg V-H genes by AIDS-associated B-cell lymphomas suggests that antigenic stimulation contributes to lymphomagenesis in patients with AIDS. (C) 1996 by The American Society of Hematology. C1 UNIV CALIF SAN DIEGO,DEPT MED,DIV HEMATOL ONCOL,LA JOLLA,CA 92093. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. FU NCI NIH HHS [5 RO1 CA65408-02] NR 69 TC 25 Z9 25 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 252 EP 260 PG 9 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700028 PM 8704181 ER PT J AU Humphrey, RW OBrien, TR Newcomb, FM Nishihara, H Wyvill, KM Ramos, GA Saville, MW Goedert, JJ Straus, SE Yarchoan, R AF Humphrey, RW OBrien, TR Newcomb, FM Nishihara, H Wyvill, KM Ramos, GA Saville, MW Goedert, JJ Straus, SE Yarchoan, R TI Kaposi's sarcoma (KS)-associated herpesvirus-like DNA sequences in peripheral blood mononuclear cells: Association with KS and persistence in patients receiving anti-herpesvirus drugs SO BLOOD LA English DT Article ID INFECTION; VIRUS; AIDS AB Herpesvirus-like DNA sequences (KSHV/HHV-8) have recently been described in AIDS-associated Kaposi's sarcoma (KS) lesions. Many questions remain regarding the role of this virus in KS and the therapeutic implications of this finding. In the current study, KSHV/HHV-8 DNA was detected in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus (HIV)-infected patients with KS (34/98) more often than in HIV-infected individuals without KS (12/64, P = .03). The detection of KSHV/HHV-8 DNA did not correlate with the CD4 lymphocyte count. Five patients demonstrated KSHV/HHV-8 DNA in their PBMCs during administration of intravenous foscarnet and/or ganciclovir. The continued detection of KSHV/HHV-8 DMA in the PBMCs of patients receiving these anti-herpesvirus drugs has potential implications regarding the virus-cell relationship of KSHV/HHV-8, as well as for the value of these drugs in treating or preventing KS, but additional studies are needed. C1 NCI,VIRAL EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP Humphrey, RW (reprint author), NCI,MED BRANCH,NIH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 18 TC 58 Z9 61 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1996 VL 88 IS 1 BP 297 EP 301 PG 5 WC Hematology SC Hematology GA UV297 UT WOS:A1996UV29700033 PM 8704186 ER PT J AU Agostini, HT Gullotta, F Lucas, S Wamukota, W Ryschkewitsch, CF Stoner, GL AF Agostini, HT Gullotta, F Lucas, S Wamukota, W Ryschkewitsch, CF Stoner, GL TI Two African cases of progressive multifocal leukoencephalopathy SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 NIH,LENP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 1996 VL 6 IS 3 BP 349 EP 349 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UY659 UT WOS:A1996UY65900018 ER PT J AU Qin, ZH Wang, YM Chase, TN AF Qin, ZH Wang, YM Chase, TN TI Stimulation of N-methyl-D-aspartate receptors induces apoptosis in rat brain SO BRAIN RESEARCH LA English DT Article DE N-methyl-D-aspartate; quinolinic acid; excitotoxicity; apoptosis; DNA fragmentation; neurodegeneration; Huntington's disease ID PROGRAMMED CELL-DEATH; AMYOTROPHIC-LATERAL-SCLEROSIS; INDUCED NEURONAL DEATH; CENTRAL-NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; QUINOLINIC ACID; DNA FRAGMENTATION; OXIDATIVE STRESS; NICK-TRANSLATION; NMDA RECEPTORS AB To evaluate the contribution of apoptotic mechanisms to excitotoxin-induced neurodegeneration as well as to characterize the glutamate receptor subtypes involved, biochemical and morphological effects of intrastriatally administered NMDA receptor agonist N-methyl-D-aspartate (NMDA) or quinolinic acid (QA) were studied. Receptor autoradiography showed that NMDA (75-300 nmol) caused a loss of 18-68% of striatal D-1 dopamine (DA) and 10-43% of NMDA receptors 7 days after drug administration. Treatment with QA (60-240 nmol) also led to a loss of 60-73% of D-1 DA and 37-44% of NMDA receptors in the ipsilateral striatum. Agarose gel electrophoresis revealed that both NMDA and QA induced internucleosomal DNA fragmentation in the striatum 12 to 48 h after drug administration. NMDA- and QA-induced internucleosomal DNA fragmentation was attenuated by the protein synthesis inhibitor cycloheximide in a dose-dependent manner. Terminal transferase-mediated deoxyuridine triphosphate (d-UTP)-digoxigenin nick end labeling (TUNEL)-positive nuclei were found in the ipsilateral striatum in response to NMDA or QA treatment. In addition, many fragmented nuclei were observed in the NMDA or QA-treated striatum and propidium iodide staining showed profound nuclear condensation in the NMDA or QA-treated striatum. NMDA- and QA-induced internucleosomal DNA fragmentation and TUNEL-positive nuclei as well as nuclear condensation were abolished by the NMDA receptor antagonist MK-801, but not by the AMPA/KA receptor antagonist NBQX. MK-801, but not NBQX, also prevented NMDA or QA-induced striatal cell death. These results suggest that apoptotic mechanisms are involved in excitotoxin-induced striatal cell death. The initiation of an apoptotic cascade by NMDA or QA appears to be mediated by stimulation of NMDA but not AMPA/KA receptors. C1 NINCDS,EXPTL THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NR 55 TC 79 Z9 86 U1 0 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 JUL 1 PY 1996 VL 725 IS 2 BP 166 EP 176 DI 10.1016/S0006-8993(96)00200-4 PG 11 WC Neurosciences SC Neurosciences & Neurology GA UX557 UT WOS:A1996UX55700003 PM 8836522 ER PT J AU Parshad, R Price, FM Bohr, VA Cowans, KH Zujewski, JA Sanford, KK AF Parshad, R Price, FM Bohr, VA Cowans, KH Zujewski, JA Sanford, KK TI Deficient DNA repair capacity, a predisposing factor in breast cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE DNA repair; chromatid breaks; breast cancer ID PHASE-X-IRRADIATION; PIGMENTOSUM COMPLEMENTATION GROUP; ATAXIA TELANGIECTASIA CELLS; INDUCED CHROMATID DAMAGE; LI-FRAUMENI SYNDROME; XERODERMA-PIGMENTOSUM; NEOPLASTIC TRANSFORMATION; COCKAYNES-SYNDROME; ULTRAVIOLET-LIGHT; PRONE FAMILY AB Women with breast cancer and a family history of breast cancer and some with sporadic breast cancer are deficient in the repair of radiation-induced DNA damage compared with normal donors with no family history of breast cancer. DNA repair was measured indirectly by quantifying chromatid breaks in phytohaemagglutinin (PHA)-stimulated blood lymphocytes after either X-irradiation or UV-C exposure, with or without post treatment with the DNA repair inhibitor, 1-beta-D-arabinofuranosylcytosine (ara-C). We have correlated chromatid breaks with unrepaired DNA strand breaks using responses to X-irradiation of cells from xeroderma pigmentosum patients with well-characterised DNA repair defects or responses of repair-deficient mutant Chinese hamster ovary (CHO) cells with or without transfected human DNA repair genes. Deficient DNA repair appears to be a predisposing factor in familial breast cancer and in some sporadic breast cancers. C1 NCI,NIH,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20059. NIA,NIH,GENET MOLEC LAB,BALTIMORE,MD 21224. NCI,NIH,DIV CANC TREATMENT,BETHESDA,MD 20892. NR 39 TC 160 Z9 165 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1996 VL 74 IS 1 BP 1 EP 5 DI 10.1038/bjc.1996.307 PG 5 WC Oncology SC Oncology GA UU494 UT WOS:A1996UU49400001 PM 8679441 ER PT J AU Mitchell, JB Cook, JA Krishna, MC DeGraff, W Gamson, J Fisher, J Christdodoulou, D Wink, DA AF Mitchell, JB Cook, JA Krishna, MC DeGraff, W Gamson, J Fisher, J Christdodoulou, D Wink, DA TI Radiation sensitisation by nitric oxide releasing agents SO BRITISH JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 9th International Conference on Chemical Modifiers of Cancer Treatment CY AUG 22-26, 1995 CL CHRISTCHURCH, ENGLAND SP Canc Res Campaign, Sanofi Winthrop DE nitric oxide; radiation; hypoxia; sensitisation ID MECHANISM; NO AB Previous studies have shown that nitric oxide (NO) sensitises hypoxic cells to ionising radiation. In the present study, four different nitric oxide (NO) donor agents were evaluated for both NO release and hypoxic radiosensitisation. The S-nitrosothiol NO donor agents, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), were shown to release sustained NO concentrations (mu M) and significantly radiosensitise hypoxic cells. The extent of hypoxic radiosensitisation by both of these agents at 1.0 mM concentration was similar to that obtained with molecular oxygen. In contrast, neither 3-morpholino-sydnonimine (SIN-1) nor sodium nitroprusside (SNP) released detectable NO concentrations and neither agent enhanced the hypoxic radiation response to the extent of that observed for GSNO or SNAP. NO-mediated hypoxic cell radiosensitisation by NO donor drugs may offer a new approach for clinical consideration, particularly if such agents can be selectively delivered to hypoxic cells. C1 JOHNSON MATHEY INC,BIOMED DIV,W CHESTER,PA 19380. RP Mitchell, JB (reprint author), NCI,RADIAT BIOL BRANCH,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892, USA. NR 18 TC 19 Z9 21 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1996 VL 74 SU 27 BP S181 EP S184 PG 4 WC Oncology SC Oncology GA UX775 UT WOS:A1996UX77500042 PM 8763876 ER PT J AU Okunieff, P Wu, T Huang, K Ding, I AF Okunieff, P Wu, T Huang, K Ding, I TI Differential radioprotection of three mouse strains by basic or acidic fibroblast growth factor SO BRITISH JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 9th International Conference on Chemical Modifiers of Cancer Treatment CY AUG 22-26, 1995 CL CHRISTCHURCH, ENGLAND SP Canc Res Campaign, Sanofi Winthrop DE cytokine; total body irradiation; radiation effect; bone marrow ID COLONY-STIMULATING FACTOR; ENDOTHELIAL-CELLS; PROGENITOR CELLS; RADIATION; SURVIVAL; CSF AB Recently we found that human recombinant basic fibroblast growth factor (FGF(2)) radioprotected C3H/HeNCr mice after whole body irradiation (WBI). The purpose of the present study was to compare the in vivo radioprotective effects of human recombinant acidic fibroblast growth factor (FGF(1)) or FGF(2) in three strains of mice (C3H/HeNCr, BALB/CAn, C57BL/6). In vivo administration of 6 mu g/mouse of FGF(1) or FGF(2) pre- or post- WBI significantly protected only C3H and BALB/C mice. Dose modification factor was: C3H(FGF(1/2)) 1.09 +/- 0.02/1.14 +/- 0.04; BALB/C(FGF(1/2)) 1.13 + /- 0.02/1.15 +/- 0.01. Response was minimal or absent in C57 mice (FGF(2) 1.02 +/- 0.02). Increasing the FGF dose above 12 mu g/mouse did not increase radioprotection in any strain. In single radiation dose studies, FGF(2) was more potent than FGF(1) in C3H mice; FGF(1) and FGF(2) were equipotent in BALB/C mice; and both had minimal effect in C57 mice. Significant radioprotection occurred in only two of the three strains of mice studied. We therefore suggest caution in applying mouse radioprotection data to other species. RP Okunieff, P (reprint author), NCI,NIH,RADIAT ONCOL BRANCH,BLDG 10,B3B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 19 Z9 19 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1996 VL 74 SU 27 BP S105 EP S108 PG 4 WC Oncology SC Oncology GA UX775 UT WOS:A1996UX77500025 PM 8763859 ER PT J AU Okunieff, P deBie, J Dunphy, EP Terris, DJ Hockel, M AF Okunieff, P deBie, J Dunphy, EP Terris, DJ Hockel, M TI Oxygen distributions partly explain the radiation response of human squamous cell carcinomas SO BRITISH JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 9th International Conference on Chemical Modifiers of Cancer Treatment CY AUG 22-26, 1995 CL CHRISTCHURCH, ENGLAND SP Canc Res Campaign, Sanofi Winthrop DE hypoxia; oxygenation; human tumours; tumour control probability ID UTERINE CERVIX; HYPERBARIC-OXYGEN; ADVANCED CANCER; HUMAN-TUMORS; RADIOTHERAPY; THERAPY; TENSION; RADIOCURABILITY; SURVIVAL; TRIAL AB The oxygen tension of human tumours has often been thought to alter tumour response to radiation therapy. The purpose of this analysis is to determine to what extent the observed results of radiotherapy fit predictions based on in situ human tumour pO(2) distributions. The radiation dose-response curve for patients treated with radiation alone for squamous cell cancers of the cervix and oropharynx were calculated based on published data. pO(2) histograms were obtained from 30 women with cervical cancer and 11 patients with neck nodes from head and neck cancers. An average of 76+/-35 (range 28-174) measurements were made from each patient. Hypoxia was assumed to be a purely dose-modifying factor with a maximum OER of 2.5. Assuming patients are treated with daily radiation doses of 2 Gy, the squamous cell carcinoma alpha/beta ratio is 10 Gy, and that tumours have a mean of 10(8) clonogens, it was possible to estimate tumour control probability. Tumour oxygenation was an extremely important modifier of the slope of the dose-response curve and alone was sufficient to account for the slope of the clinically observed dose-response curve for neck nodes. The response curve for uterine cervical cancers is very shallow, and the oxygen distribution did not completely account for heterogeneity of response of these tumours. The results support the conclusion that oxygen tension distribution is an important modifier of human radiation treatment response. C1 SANTA CLARA VALLEY MED CTR,DEPT RADIAT ONCOL,SAN JOSE,CA. SANTA CLARA VALLEY MED CTR,DEPT OTOLARYNGOL,SAN JOSE,CA. UNIV MAINZ,DEPT OBSTET & GYNECOL,D-55131 MAINZ,GERMANY. RP Okunieff, P (reprint author), NCI,RADIAT ONCOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10 RM B3B69,BETHESDA,MD 20892, USA. NR 32 TC 3 Z9 3 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1996 VL 74 SU 27 BP S185 EP S190 PG 6 WC Oncology SC Oncology GA UX775 UT WOS:A1996UX77500043 ER PT J AU Wang, XW Jia, L Bennett, WP Elmore, LW Harris, CC AF Wang, XW Jia, L Bennett, WP Elmore, LW Harris, CC TI p53 tumor suppressor gene: At the crossroads of molecular carcinogenesis, molecular epidemiology and cancer therapy SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. RI Wang, Xin/B-6162-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1996 VL 74 SU 28 BP SP17 EP SP17 PG 1 WC Oncology SC Oncology GA UX776 UT WOS:A1996UX77600011 ER PT J AU Thorgeirsson, SS SantoniRugiu, E AF Thorgeirsson, SS SantoniRugiu, E TI Transgenic mouse models in carcinogenesis: Interaction of c-myc with transforming growth factor alpha and hepatocyte growth factor in hepatocarcinogenesis SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Festschrift in Honour of Professor Sir Colin Dollery CY JUN 20-21, 1996 CL HAMMERSMITH HOSPITAL, ROYAL POSTGRAD MED SCH, LONDON, ENGLAND HO HAMMERSMITH HOSPITAL, ROYAL POSTGRAD MED SCH DE transgenic mouse; oncogenes; suppressor genes; carcinogenesis ID TUMOR CYTOTOXIC FACTOR; MET HGF RECEPTOR; SCATTER FACTOR; EPITHELIAL-CELLS; HEPATOCELLULAR-CARCINOMA; HEPATIC DIFFERENTIATION; HUMAN FIBROBLASTS; LIVER NEOPLASIA; MESSENGER-RNA; TGF-ALPHA AB 1 Overexpression of the c-myc oncogene is associated with a variety of both human and experimental tumours, and cooperation of other oncogenes and growth factors with the myc family are critical in the evolution of the malignant phenotype. 2 Double transgenic mice bearing fusion genes consisting of mouse albumin enhancer/promoter-mouse c-myc cDNA and mouse metallothionein 1 promoter-human transforming growth factor (TGF-alpha) cDNA were generated to investigate the interaction of these genes in hepatic oncogenesis and to provide a general paradigm for characterizing the interaction of nuclear oncogenes and growth factors in tumourigenesis. 3 Coexpression of c-myc and TGF-alpha as transgenes in the mouse liver resulted in a tremendous acceleration of neoplastic development in this organ as compared to expression of either of these transgenes alone. The two distinct cellular reactions that occurred in the liver of the double transgenic mice prior to the appearance of liver tumours were dysplastic and apoptotic changes in the existing hepatocytes followed by emergence of multiple focal lesions composed of both hyperplastic and dysplastic cell populations. 4 These observations suggest that the interaction of c-myc and TGF-alpha, during development of hepatic neoplasia contributes to the selection and expansion of the preneoplastic cell populations which consequently increases the probability of malignant conversion. 5 We have now extended these studies and examined the interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in the transgenic mouse model. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Similarly, tumour promotion by phenobarbitone was completely inhibited in the c-myc/HGF double transgenic mice whereas phenobarbitone was an effective tumour promoter in the c-myc single transgenic mice. 6 The results indicate that HGF may function as a tumour suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. Furthermore, we show for the first time that interaction of c-myc with HGF or TGF-alpha results in profoundly different outcomes of the neoplastic process in the liver. RP Thorgeirsson, SS (reprint author), NCI,EXPTL CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BLDG 37,ROOM 3C28,37 CONVENT DR MSC4255,BETHESDA,MD 20892, USA. NR 84 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD JUL PY 1996 VL 42 IS 1 BP 43 EP 52 DI 10.1046/j.1365-2125.1996.03748.x PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UU197 UT WOS:A1996UU19700008 PM 8807143 ER PT J AU Hayashi, S Chan, CC Gazzinelli, RT Pham, NH Cheung, MK Roberge, FG AF Hayashi, S Chan, CC Gazzinelli, RT Pham, NH Cheung, MK Roberge, FG TI Protective role of nitric oxide in ocular toxoplasmosis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ANTI-MICROBIAL ACTIVITY; IFN-GAMMA; TNF-ALPHA; ACTIVATED MACROPHAGES; MURINE MACROPHAGES; L-ARGININE; T-CELLS; GONDII; CYTOKINES; EXPRESSION AB Aim-To evaluate the role of nitric oxide (NO) in ocular involvement during systemic toxoplasmosis. Methods-C57B1/6 mice were infected with Toxoplasma gondii strain ME49. The synthesis of NO was Inhibited by an intraperitoneal injection of aminoguanidine every 8 hours, starting on the day of infection. Control infected mice received phosphate buffered saline vehicle alone. After 14 days, the ocular lesions were evaluated by histopathological examination. The expression of NO synthase induced in the spleen by toxoplasma infection was evaluated by immunostaining, The production of NO by the spleen cells of infected mice was measured by the colorimetric assay of Griess in the supernatant of cultures stimulated with toxoplasma antigen or concanavalin A. Results-The inhibition of NO production in T gondii infected mice resulted, in a marked increase in the symptoms of ocular inflammation, We observed a strong induction of NO synthase expression in the spleen of infected animals, in culture, the spleen cells from these mice produced high levels of NO in response to T gondii antigens. This elevation of NO synthesis was suppressed in the presence of aminoguanidine. Conclusion-This study indicates that NO plays a crucial role in the protection against T gondii infection as reflected by the severity of the ocular involvement. C1 NEI,NIH,IMMUNOL LAB,BETHESDA,MD 20892. UNIV FED MINAS GERAIS,DEPT BIOCHEM & IMMUNOL,BELO HORIZONT,MG,BRAZIL. NR 39 TC 23 Z9 25 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUL PY 1996 VL 80 IS 7 BP 644 EP 648 DI 10.1136/bjo.80.7.644 PG 5 WC Ophthalmology SC Ophthalmology GA UY152 UT WOS:A1996UY15200015 PM 8795379 ER PT J AU GuexCrosier, Y Wittwer, AJ Roberge, FG AF GuexCrosier, Y Wittwer, AJ Roberge, FG TI Intraocular production of a cytokine (CINC) responsible for neutrophil infiltration in endotoxin induced uveitis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CD11B CD18; CELL-LINE; RAT; EXPRESSION; CHEMOATTRACTANT; INTERLEUKIN-8; RECEPTOR; ANTIGEN; LIPOPOLYSACCHARIDE AB Aims/background-The subcutaneous injection of bacterial endotoxin in Lewis rats produces an acute intraocular inflammation evolving over a 24 hour period. This endotoxin induced uveitis (EIU) is characterised by a biphasic protein exudation and a cellular infiltrate composed of macrophages and polymorphonuclear neutrophils (PMNs). This model was used to study the mechanism of cellular infiltration in ocular inflammation. Methods-EIU was induced by a subcutaneous injection of lipopolysaccharide (LPS) (S typhimurium) at 350 mu g/kg. The levels of cytokine induced neutrophil chemoattractant (CINC) were measured every 2 hours in the serum and in the aqueous humour by ELISA. The intraocular inflammation was quantified by protein measurement and leucocyte counting. Results-The kinetics of CINC production in the systemic circulation showed a rapid rise, peaking 2 hours after LPS injection, followed by a progressive decline over the next 8 hours. In the eye, the CINC levels increased above the serum levels 10 hours after EIU induction corresponding to the time of cellular infiltration. When leucocyte entry in the eye was inhibited by 56% and 64% with an antiadhesion molecule antibody, there was only a slight reduction in the aqueous humour CINC levels of 9% and 16%, respectively, indicating that CINC was produced by ocular tissue cells. The specific effect of CINC in the eye was confirmed when a direct intraocular injection of 250 ng of purified CINC was followed by significant PMN infiltration, in the absence of protein exudation. Conclusion-The data indicate that the production of the CINC chemotactic factor by ocular tissue participates in the inflammatory reaction in EIU. C1 NEI,NIH,BETHESDA,MD 20892. MONSANTO CO,MONSANTO CORP RES,ST LOUIS,MO. NR 39 TC 30 Z9 30 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUL PY 1996 VL 80 IS 7 BP 649 EP 653 DI 10.1136/bjo.80.7.649 PG 5 WC Ophthalmology SC Ophthalmology GA UY152 UT WOS:A1996UY15200016 PM 8795380 ER PT J AU Sugden, D Anwar, N Klein, DC AF Sugden, D Anwar, N Klein, DC TI Rat pineal alpha(1)-adrenoceptor subtypes: Studies using radioligand binding and reverse transcription-polymerase chain reaction analysis SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE pineal; alpha(1)-adrenoceptor subtypes; mRNA expression; reverse transcription-polymerase chain reaction (RT-PCR) ID ALPHA-1-ADRENERGIC RECEPTOR SUBTYPES; ALPHA(1C)-ADRENERGIC RECEPTOR; MOLECULAR-CLONING; ADRENERGIC REGULATION; N-ACETYLTRANSFERASE; ALPHA(1A) SUBTYPE; EXPRESSION; CDNA; STIMULATION; CALCIUM AB 1 The pharmacological characteristics of alpha(1)-adrenoceptor binding sites in rat pineal gland membranes, detected by use of a selective alpha(1)-adrenoceptor antagonist ([I-125]-iodo-2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone, [I-125]-HEAT), were investigated with the alkylating agent, chloroethylclonidine (CEC), and in competition experiments with a number of adrenoceptor agonists and antagonists. 2 Chloroethylclonidine (CEC) treatment (10 mu M, 10 min) of rat pineal membranes inactivated similar to 70% of specific [I-125]-HEAT binding sites. Higher concentrations of CEC (up to 100 mu M) or longer treatment periods (upto 40 min) were no more effective. 3 Adrenoceptor agonists and antagonists competitively inhibited [I-125]-HEAT binding with Hill coefficients close to unity indicating a single alpha(1)-adrenoceptor subtype is present. The affinity (K-i) of subtype selective agonists (oxymetazoline, SDZ NVI-085) and antagonists (5-methylurapidil, WB4101, benoxathian, phentolamine) was consistent with binding to an alpha(1B)-adrenoceptor subtype. 4 The (-)- and (+)-enantiomers of niguldipine had an equal and low affinity for al-adrenoceptor binding sites both in untreated (log K-i-6.66 and -6.90 respectively) and CEC-treated membranes in which similar to 70% of sites had been inactivated (log K-i-6.41 and -6.86 respectively). This indicates that the small proportion of alpha(1)-adrenoceptors insensitive to CEC are not alpha(1A)-adrenoceptors. 5 mRNA was isolated from rat pinealocytes, cDNA was synthesized and then amplified by the polymerase chain reaction with alpha(1)-adrenoceptor subtype specific primers. These experiments identified both alpha(1A)- and alpha(1B)-adrenoceptor mRNA, but not alpha(1D)-mRNA in rat pinealocytes, although all three adrenoceptor subtypes were readily identified in rat brain cortex. 6 These data indicate that although both alpha(1A)- and alpha(1B)-adrenoceptor mRNAs are present in the pineal the major subtype of alpha(1)-adrenoceptor expressed is the alpha(1B). C1 NICHHD,SECT NEUROENDOCRINOL,LAB DEV NEUROENDOCRINOL,NIH,BETHESDA,MD 20892. RP Sugden, D (reprint author), UNIV LONDON KINGS COLL,DIV BIOMED SCI,PHYSIOL GRP,CAMPDEN HILL RD,LONDON W8 7AH,ENGLAND. NR 44 TC 8 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 1996 VL 118 IS 5 BP 1246 EP 1252 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UX111 UT WOS:A1996UX11100021 PM 8818350 ER PT J AU Stavri, PZ AF Stavri, PZ TI Medical problem attributes and information seeking questions SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID DECISION-MAKING; NEEDS; PHYSICIANS; GENERATION; KNOWLEDGE AB This study was designed to explore the relationship between certain attributes of a diagnostic problem and a particular information-seeking question. Using case vignettes under experimental conditions, fifty residents in internal medicine and family practice informed the experimenter of the most important thing they would need to know to make a preliminary diagnosis. These data were classified nominally using a preexisting taxonomy. Significant results indicated that Quantification questions tend to be asked under urgent conditions and Verification questions tend to be asked when the least amount of information is presented. While the taxonomy used to classify the questions did not prove rich enough to describe information needs fully, results did suggest some consistency in question asking, a skill that could be;developed further during medical education. RP Stavri, PZ (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 41 TC 6 Z9 6 U1 0 U2 0 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JUL PY 1996 VL 84 IS 3 BP 367 EP 374 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA VG786 UT WOS:A1996VG78600008 PM 8883985 ER PT J AU Humphreys, BL AF Humphreys, BL TI Librarians and collaborative research: Toward a better scientific base for information practice SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Editorial Material ID MEDLINE RP Humphreys, BL (reprint author), NATL LIB MED,HLTH SERV RES INFORMAT,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 8 TC 5 Z9 6 U1 0 U2 2 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JUL PY 1996 VL 84 IS 3 BP 433 EP 436 PG 4 WC Information Science & Library Science SC Information Science & Library Science GA VG786 UT WOS:A1996VG78600018 PM 8883995 ER PT J AU Hall, WH AF Hall, WH TI NIH statement on cochlear implants SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Letter RP Hall, WH (reprint author), NATL INST HLTH,OFF MED APPLICAT RES,BETHESDA,MD, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUL 1 PY 1996 VL 155 IS 1 BP 20 EP 20 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UU715 UT WOS:A1996UU71500015 PM 8673981 ER PT J AU Abati, A Liotta, LA AF Abati, A Liotta, LA TI Looking forward in diagnostic pathology - The molecular superhighway SO CANCER LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; REVERSE-TRANSCRIPTASE; CELLS; DISEASE RP Abati, A (reprint author), NCI,CYTOPATHOL SECT,NIH,PATHOL LAB,BLDG 10,ROOM 2A,BETHESDA,MD 20892, USA. NR 24 TC 39 Z9 40 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 1996 VL 78 IS 1 BP 1 EP 3 PG 3 WC Oncology SC Oncology GA UR448 UT WOS:A1996UR44800001 PM 8646703 ER PT J AU Kenney, LB Nicholson, HS Brasseux, C Mills, JL Robison, LL Zeltzer, LK Meadows, AT Reaman, GH Byrne, J AF Kenney, LB Nicholson, HS Brasseux, C Mills, JL Robison, LL Zeltzer, LK Meadows, AT Reaman, GH Byrne, J TI Birth defects in offspring of adult survivors of childhood acute lymphoblastic leukemia - A Childrens Cancer Group National Institutes of Health report SO CANCER LA English DT Article DE childhood cancer; cancer survivors; late effects; birth defects; offspring of cancer survivors; acute lymphoblastic leukemia ID ACUTE LYMPHOID LEUKEMIA; LONG-TERM SURVIVORS; ADOLESCENT CANCER; FERTILITY; CYCLOPHOSPHAMIDE; ANOMALIES; PREGNANCY; THERAPY; PROGENY AB BACKGROUND. It is not known if therapy for acute lymphoblastic leukemia (ALL) during childhood increases the risk of birth defects in the offspring of adult survivors. The Childrens Cancer Group (CCG), in collaboration with the National Institutes of Health (NIH), conducted a retrospective cohort study of adults successfully treated for childhood ALL to determine if their offspring had an increased incidence of birth defects compared with the offspring of their sibling controls. METHODS. Study subjects were patients who had been enrolled on CCG ALL protocols, who were treated for ALL prior to age 20, who survived at; least 2 years, and who were at least age 18. Survivors (N = 593) and sibling controls (N = 409) were interviewed by telephone. RESULTS. The mean age of survivors was 22.6 years; the mean age of controls was 25.2 years. Among survivors, 93 (15.7%) had given birth to or fathered a total of 140 live-born offspring, (mean age, 3.4 years), and 122 (29.8%) sibling controls had given birth to or fathered a total of 228 live-born offspring (mean age, 5.9 years). There was no difference in the rate of birth defects between offspring of survivors and offspring of controls (3.6% [5 of 140] vs. 3.5% [8 of 228]; relative risk, 1.02; 95% confidence interval, 0.34, 3.05). No specific ALL therapy was associated with an increased rare of birth defects. Only female survivors reported offspring with birth defects (P = 0.0735). CONCLUSIONS. Adult survivors of childhood ALL in our study were not at greater risk for having offspring with birth defects compared with sibling controls. Although this is the largest group of ALL survivors studied to date, the number of offspring is still not large enough to detect small but significant differences in rare events such as birth defects. Studies following this cohort into later adulthood and studies of additional ALL survivors are necessary to adequately quantify the risks. (C) 1996 American Cancer Society. C1 CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. NCI,NIH,GENET EPIDEMIOL BRANCH,BETHESDA,MD. CHILDRENS NATL MED CTR,DIV BIOSTAT,WASHINGTON,DC 20010. NICHHD,NIH,EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT PEDIAT,MINNEAPOLIS,MN 55455. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. CHILDRENS HOSP PHILADELPHIA,DIV ONCOL,PHILADELPHIA,PA 19104. NR 32 TC 31 Z9 31 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 1996 VL 78 IS 1 BP 169 EP 176 DI 10.1002/(SICI)1097-0142(19960701)78:1<169::AID-CNCR23>3.0.CO;2-X PG 8 WC Oncology SC Oncology GA UR448 UT WOS:A1996UR44800023 PM 8646713 ER PT J AU Olsen, JH Hertz, H Kjaer, SK Bautz, A Mellemkjaer, L Boice, JD AF Olsen, JH Hertz, H Kjaer, SK Bautz, A Mellemkjaer, L Boice, JD TI Childhood leukemia following phototherapy for neonatal hyperbilirubinemia (Denmark) SO CANCER CAUSES & CONTROL LA English DT Article DE childhood leukemia; Denmark; neonatal hyperbilirubinemia; phototherapy ID ACUTE LYMPHOCYTIC-LEUKEMIA; EXPOSURE; PROTOPORPHYRIN; CHILDREN; CANCER AB To test the hypothesis that exposure to high intensity lightning (around 400 nanometers) in neonatal nurseries increases the incidence of childhood leukemia, over 55,120 newborn children treated with phototherapy for hyperbilirubinemia were identified from the Danish Hospital Discharge Register for 1977-89, Linkage of the roster with the national cancer registry through 1991 revealed 87 childhood cancers, whereas 85 were expected from the rates for the general population, The incidence of leukemia in 34 children was not unusual (standardized incidence ratio [SIR] = 1.2, 95 percent confidence interval [CI] = 0.8-1.7). Subgroup analyses revealed no remarkable patterns for any category of leukemia subtype, gender, or age at diagnosis, We conclude that whole-body exposure to phototherapy (420-470 nm) shortly after birth is not a significant risk factor for childhood leukemia. C1 NATL UNIV HOSP,JULIANE MARIE CTR CHILDREN WOMEN & REPROD,COPENHAGEN,DENMARK. NCI,BIOSTAT PROGRAM,BETHESDA,MD 20892. RP Olsen, JH (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,STRANDBLVD 49,DK-2100 COPENHAGEN,DENMARK. NR 14 TC 15 Z9 17 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1996 VL 7 IS 4 BP 411 EP 414 DI 10.1007/BF00052666 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UV510 UT WOS:A1996UV51000002 PM 8813428 ER PT J AU Linet, MS Gridley, G Cnattingius, S Nicholson, HS Martinsson, U Glimelius, B Adami, HO Zack, M AF Linet, MS Gridley, G Cnattingius, S Nicholson, HS Martinsson, U Glimelius, B Adami, HO Zack, M TI Maternal and perinatal risk factors for childhood brain tumors (Sweden) SO CANCER CAUSES & CONTROL LA English DT Article DE case-control study; childhood brain neoplasms; neonatal; perinatal; prenatal; Sweden ID CANCER INCIDENCE; RECORD-LINKAGE; UNITED-STATES; BIRTH-DEFECTS; CHILDREN; SMOKING; PREGNANCY; TWINS; EPIDEMIOLOGY; EXPOSURE AB Childhood brain tumors (CBT) include a diversity of rare neoplasms of largely unknown etiology. To assess possible maternal and perinatal risk factors for CBT according to subtype, we carried out a nested (within Swedish birth-cohorts, 1973-89) case-control study utilizing data from the nationwide Birth Registry. We ascertained incident brain tumor cases through linkage of the nationwide Birth and Cancer Registries and randomly selected five living controls from the former, matching each case on gender and birthdate. There were 570 CBT cases, including 205 low grade astrocytomas, 58 high grade astrocytomas, 93 medulloblastomas, 54 ependymomas, and 160 'others.' Risks for all brain tumors combined were elevated in relation to: (i) three maternal exposures - oral contraceptives prior to conception (odds ratios [OR] = 1.6, 95 percent confidence interval [CI] = 1.0-2.8), use of narcotics (OR = 1.3, CI = 1.0-1.6), or penthrane (OR = 1.5, CI = 1.1-2.0) during delivery); (ii) characteristics of neonatal distress (a combined variable including low one-minute Apgar score, asphyxia [OR = 1.5, CI = 1.1-2.0]) or treatments for neonatal distress (use of supplemental oxygen, ventilated on mask, use of incubator, scalp vein infusion, feeding with a jejunal tube [DR = 1.6, CI = 0.9-2.6]); and (iii) neonatal infections (OR = 2.4, CI = 1.5-4.0). Higher subtype-specific risks, observed for a few risk factors, did not differ significantly from the risk estimates for all subtypes combined for the corresponding risk factors. Childhood brain tumors were not associated significantly with other maternal reproductive, lifestyle, or disease factors; perinatal pain, anesthetic medications, birth-related complications; or with birthweight,birth defects, or early neonatal diseases. These findings suggest several new leads, but only weak evidence of brain tumor subtype-specific differences. C1 UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. UNIV UPPSALA HOSP,DEPT SOCIAL MED,UPPSALA,SWEDEN. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. UNIV UPPSALA HOSP,DEPT ONCOL,UPPSALA,SWEDEN. HARVARD UNIV,DEPT EPIDEMIOL,BOSTON,MA. CTR DIS CONTROL & PREVENT,DIV CHRON DIS CONTROL & COMMUNITY INTERVENT,ATLANTA,GA. RP Linet, MS (reprint author), NCI,DIV CANC ETIOL & GENET,EPIDEMIOL & BIOSTAT PROGRAM,EPN 415,6130 EXECUT BLVD,MSC 7368,BETHESDA,MD 20892, USA. NR 66 TC 67 Z9 68 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1996 VL 7 IS 4 BP 437 EP 448 DI 10.1007/BF00052670 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UV510 UT WOS:A1996UV51000006 PM 8813432 ER PT J AU Glynn, SA Albanes, D Pietinen, P Brown, CC Rautalahti, M Tangrea, JA Gunter, EW Barrett, MJ Virtamo, J Taylor, PR AF Glynn, SA Albanes, D Pietinen, P Brown, CC Rautalahti, M Tangrea, JA Gunter, EW Barrett, MJ Virtamo, J Taylor, PR TI Colorectal cancer and folate status: A nested case-control study among male smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NEURAL-TUBE DEFECTS; FOLIC-ACID; COLON-CANCER; ULCERATIVE-COLITIS; BIASED SELECTION; PREVENTION; ALCOHOL; RISK; METHIONINE; METABOLISM AB Evidence is accumulating that folate, a B vitamin found in green leafy vegetables, may affect the development of neoplasia. We examined the relationship between folate status and colorectal cancer in a case-control study nested within the Alpha-Tocopherol Beta-Carotene Study cohort of male smokers 50-69 years old. Serum folate was measured in 144 incident cases (91 colon, 53 rectum) and 276 controls matched to cases on baseline age, clinic, and time of blood collection. Baseline dietary folate was available from a food-use questionnaire for 386 of these men (92%). Conditional logistic regression modeling was used. No statistically significant association was observed between serum folate and colon or rectal cancer. Although a 2-fold increase in rectal cancer risk was suggested for men with serum folate >2.9 ng/ml and those in the highest quartile of energy-adjusted folate intake, there was no evidence of a monotonic dose-response, and all confidence intervals included unity. For dietary folate and colon cancer, odds ratios of 0.40 [95% confidence interval (CI), 0.16-0.96], 0.34 (95% CI, 0.13-0.88), and 0.51 (95% CI, 0.20-1.31) were obtained for the second through fourth quartiles of energy-adjusted folate intake, respectively, compared to the first (P for trend = 0.15). Furthermore, men with a high-alcohol, low-folate, low-protein diet were at higher risk for colon cancer than men who consumed a low-alcohol, high-folate, high-protein diet (OR, 4.79; 95% CI, 1.36-16.93). This study suggests a possible association between low folate intake and increased risk of colon cancer (but not rectal cancer) and highlights the need for further studies that measure dietary folate and methionine, along with biochemical measures of folate (i.e., erythrocyte and serum), homocysteine, and vitamin B-12. C1 NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. NATL PUBL HLTH INST,SF-00300 HELSINKI,FINLAND. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20910. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165.] NR 58 TC 156 Z9 159 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 1996 VL 5 IS 7 BP 487 EP 494 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UW619 UT WOS:A1996UW61900001 PM 8827351 ER PT J AU Dorgan, JF Longcope, C Stephenson, HE Falk, RT Miller, R Franz, C Kahle, L Campbell, WS Tangrea, JA Schatzkin, A AF Dorgan, JF Longcope, C Stephenson, HE Falk, RT Miller, R Franz, C Kahle, L Campbell, WS Tangrea, JA Schatzkin, A TI Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HORMONE-BINDING GLOBULIN; HUMAN MAMMARY-TUMORS; POSTMENOPAUSAL WOMEN; AROMATASE-ACTIVITY; STEROID-HORMONES; DEHYDROEPIANDROSTERONE SULFATE; TESTOSTERONE; ESTRADIOL; TISSUE; ANDROSTENEDIONE AB To evaluate the relation of serum sex hormones to breast cancer risk, we conducted a prospective nested case-control study using the Breast Cancer Serum Bank (Columbia, MO), This bank included serum from 3375 postmenopausal women free of cancer and not taking replacement estrogens when they donated blood between 1977 and 1987, Of these, 71 were diagnosed subsequently with breast dancer, For each case, two women alive and free of cancer at the age of the case's diagnosis and matched to the case on age and on date and time of day of blood collection were selected as controls, The median age of subjects at blood collection was 62 years, and the time from blood collection to diagnosis ranged from less than 1 to 9.5 years, with a median of 2.9 years, Postmenopausal women with elevated serum levels of total and non-sex hormone-binding globulin-bound E2 were at an increased risk of developing breast cancer, For non-sex hormone-binding globulin-bound E2, risks were elevated 4-5-fold for women in the upper three quartiles relative to those in the lowest quartile, Although breast cancer was not related to estrone or estrone sulfate concentration, the ratio of estrone sulfate to estrone was significantly inversely associated with risk, suggesting that women who develop breast cancer may be less able to metabolize estrone to its less active form, Serum testosterone was significantly positively associated with postmenopausal breast cancer; the relative risk for women in the highest versus the lowest quartile was 6.2 (95% confidence interval, 2.0-19.0), Our results support the hypothesis that prediagnostic serum estrogens and androgens are related to the subsequent diagnosis of breast cancer in postmenopausal women. C1 UNIV MASSACHUSETTS,SCH MED,DEPT OBSTET & GYNECOL,WORCESTER,MA 01655. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01655. UNIV MISSOURI,HLTH SCI CTR,DEPT SURG,COLUMBIA,MO 65212. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. ELLIS FISCHEL CANC CTR,CANC SCREENING SERV,COLUMBIA,MO 65203. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. RP Dorgan, JF (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,ROOM 211,6130 EXECUT BLVD,MSC 7326,BETHESDA,MD 20892, USA. NR 40 TC 186 Z9 189 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 1996 VL 5 IS 7 BP 533 EP 539 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UW619 UT WOS:A1996UW61900008 PM 8827358 ER PT J AU Lanza, E Schatzkin, A BallardBarbash, R Corle, D Clifford, C Paskett, E Hayes, D Bote, E Caan, B Shike, M Weissfeld, J Slattery, M Mateski, D Daston, C AF Lanza, E Schatzkin, A BallardBarbash, R Corle, D Clifford, C Paskett, E Hayes, D Bote, E Caan, B Shike, M Weissfeld, J Slattery, M Mateski, D Daston, C TI The polyp prevention trial II: Dietary intervention program and participant baseline dietary characteristics (vol 5, pg 385, 1996) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Correction, Addition C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. SUNY BUFFALO,SCH MED & BIOMED SCI,BUFFALO,NY. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,HINES,IL 60141. KAISER FDN RES INST,OAKLAND,CA. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV UTAH,SALT LAKE CITY,UT. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. WESTAT CORP,ROCKVILLE,MD. RP Lanza, E (reprint author), NCI,BETHESDA,MD 20892, USA. NR 1 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 1996 VL 5 IS 7 BP 584 EP 584 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UW619 UT WOS:A1996UW61900015 ER PT J AU Wroblewski, JM Lay, LT VanZant, G Phillips, G Seth, P Curiel, D Meeker, TC AF Wroblewski, JM Lay, LT VanZant, G Phillips, G Seth, P Curiel, D Meeker, TC TI Selective elimination (purging) of contaminating malignant cells from hematopoietic stem cell autografts using recombinant adenovirus SO CANCER GENE THERAPY LA English DT Article DE purging; contaminating malignant cells; hematopoietic stem cell autografts; recombinant adenovirus ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; GENE-THERAPY; BREAST-CANCER; APOPTOSIS; VECTOR; CHEMOTHERAPY; ENGRAFTMENT; MARKING; RELAPSE AB In this work we have explored the use of adenoviral vectors for the purging of cancer cells from hematopoietic stem cell (HSC) autografts. We showed that a recombinant adenovirus expressing the herpes simplex-1 thymidine kinase gene (AD-tk) plus ganciclovir (GCV) killed HELA cells more effectively than did GCV alone. HELA cells were then mixed with human HSCs and exposed to AD-tk/GCV. AD-tk/GCV reduced the number of HELA colonies to 4% of control values, with no detectable reduction in the hematopoietic progenitor, colony forming unit-granulocyte/monocyte (CFU-GM). Similar studies of the JB6 non-Hodgkins lymphoma cell line showed a reduction to 5% of controls; studies of MCF-7, a breast carcinoma cell line, showed a reduction to 30% of controls, with no CFU-CM toxicity. Thus, AD-tk mediated selective killing of contaminating tumor cells. We also evaluated a recombinant adenovirus encoding the tumor suppressor gene p53 (AD-p53). AD-p53 was able to selectively kill all three cell lines (reducing tumor colonies approximately 100-fold) without any toxicity to CFU-GM. Although both AD-tk/GCV and AD-p53 were effective in these experiments,AD-p53 seemed to be more potent. Adenoviral vectors show promise for selectively targeting cancer cells that contaminate HSC autografts. C1 UNIV KENTUCKY,MARKEY CANC CTR,DIV HEMATOL ONCOL,LEXINGTON,KY 40536. UNIV KENTUCKY,DEPT MED,LEXINGTON,KY 40536. UNIV KENTUCKY,DEPT BIOCHEM,LEXINGTON,KY 40536. UNIV KENTUCKY,DEPT PATHOL,LEXINGTON,KY 40536. NCI,MED BRANCH,MED BREAST SECT,NIH,BETHESDA,MD 20892. UNIV ALABAMA,GENE THERAPY PROGRAM,BIRMINGHAM,AL. NR 26 TC 25 Z9 25 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUL-AUG PY 1996 VL 3 IS 4 BP 257 EP 264 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA VA441 UT WOS:A1996VA44100006 PM 8853551 ER PT J AU Ferguson, AW Flatow, U MacDonald, NJ Larminat, F Bohr, VA Steeg, PS AF Ferguson, AW Flatow, U MacDonald, NJ Larminat, F Bohr, VA Steeg, PS TI Increased sensitivity to cisplatin by nm23-transfected tumor cell lines SO CANCER RESEARCH LA English DT Article ID INTERSTRAND CROSS-LINKS; HUMAN BREAST-CANCER; NM23 PROTEIN EXPRESSION; GOOD PROGNOSIS; GENE; REPAIR; TRANSFECTION; ASSOCIATION; CARCINOMAS; DNA AB We report a functional link between expression of the metastasis suppressor gene nm23 and cancer cell sensitivity to the alkylating agent cisplatin. Cisplatin was 2-15-fold more inhibitory to the growth in vitro of nm23 transfectants of the K-1735 TK murine melanoma, MDA-MB-435 human breast carcinoma, and OVCAR-3 human ovarian carcinoma cell lines as compared to matched control transfectants. Administration of a single dose of cisplatin i.v. after injection of control- or nm23-1-transfected K-1735 TK melanoma cells resulted in a more pronounced inhibition of pulmonary metastatic colonization by the nm23-1 transfectants. The mechanism of nm23-dependent sensitivity to cisplatin is unknown, but was correlated with increased formation of interstrand DNA cross-links in nm23-H1 transfected breast carcinoma cells. These data suggest that elevation of tumor cell nm23 expression may be considered as a potential therapeutic strategy in combination with cisplatin treatment. C1 NCI,WOMENS CANC SECT,PATHOL LAB,BETHESDA,MD 20892. NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. NR 29 TC 35 Z9 42 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1996 VL 56 IS 13 BP 2931 EP 2935 PG 5 WC Oncology SC Oncology GA UT398 UT WOS:A1996UT39800013 PM 8674043 ER PT J AU Carlson, BA Dubay, MM Sausville, EA Brizuela, L Worland, PJ AF Carlson, BA Dubay, MM Sausville, EA Brizuela, L Worland, PJ TI Flavopiridol induces G(1) arrest with inhibition of cyclin-dependent kinase (CDK)2 and CDK4 in human breast carcinoma cells SO CANCER RESEARCH LA English DT Article ID RETINOBLASTOMA GENE; CDC2 KINASE; PROTEIN; PHOSPHORYLATION; P53; IDENTIFICATION; TYR15; P21 AB Flavopiridol (L86-8275), a N-methylpiperidinyl, chlorophenyl flavone, can inhibit cell cycle progression in either G(1), or G(2) and is a potent cyclin-dependent kinase (CDK) 1 inhibitor, In this study, we used MCF-7 breast carcinoma cells that are wild type for p53 and pRb positive and contain CDM-cyclin D1 and MDA-MB-468 breast carcinoma cells that are mutant p53, pRb negative, and lack CDK4-cyclin D1 to investigate the G(1) arrest produced by Flavopiridol. Recombinant CDK4-cyclin D1 was inhibited potently by Flavopiridol (K-iapp, 65 nM), competitive with respect to ATP. Surprisingly, CDK4 immunoprecipitates derived from Flavopiridol-treated MCF-7 cells (3 h, 300 nM Flavopiridol) had an approximately 3-fold increased kinase activity compared with untreated cells. Cyclin D and CDK4 levels were not different at 3 h, but cyclin D levels and CDK4 kinase activity decreased thereafter. The phosphorylation state of pRb was shifted from hypercoincident to hypocoincident with the development of G(1) arrest. Asynchronous MDA-MB-468 cells were inhibited in cell cycle progression at both G(1) and G(2) by Flavopiridol. Flavopiridol inhibited the in vitro kinase activity of CDK2 using an immune complex kinase assay (IC50, 100 nM at 400 mu M ATP). Immunoprecipitated CDK2 kinase activity from either MCF-7 or MDA-MB-468 cells exposed to Flavopiridol (300 nM) for increasing time showed an initial increased activity (approximately 1.5-fold at 3 h) compared with untreated cells, followed by a loss of kinase activity to immeasurable levels by 24 h. This increased immunoprecipitated kinase activity was dependent on the Flavopiridol concentration added to intact cells and was associated with a reduction of CDK2 tyrosine phosphorylation. Cyclin E and A levels were not altered to the same extent as cyclin D, and neither CDK4 nor CDK2 levels were changed in response to Flavopiridol. Inhibition of the CDK4 and/or CDK2 kinase activity by Flavopiridol can therefore account for the G(1) arrest observed after exposure to Flavopiridol. C1 MITOTIX INC,CAMBRIDGE,MA 02139. NCI,BIOL CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 62 TC 427 Z9 436 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1996 VL 56 IS 13 BP 2973 EP 2978 PG 6 WC Oncology SC Oncology GA UT398 UT WOS:A1996UT39800021 PM 8674031 ER PT J AU Shibata, MA Maroulakou, IG Jorcyk, CL Gold, LG Ward, JM Green, JE AF Shibata, MA Maroulakou, IG Jorcyk, CL Gold, LG Ward, JM Green, JE TI p53-independent apoptosis during mammary tumor progression in C3(1)/SV40 large T antigen transgenic mice: Suppression of apoptosis during the transition from preneoplasia to carcinoma SO CANCER RESEARCH LA English DT Article ID WILD-TYPE P53; GROWTH-REGULATION; PROTEIN; CELLS; MUTANT; POINT; SV40; LINE; GENE AB Alterations in apoptosis and associated mechanisms during mammary tumor progression were investigated in transgenic mice expressing the SV40 large T antigen (T-AG) driven by the rat prostatic steroid-binding protein C3(1) 5'-flanking region. Apoptosis levels, assessed by in situ end labeling, were low in normal mammary epithelial cells, highest in atypical hyperplasias (preneoplastic lesions), and less pronounced in adenocarcinomas. Preneoplastic cells maintain the ability to undergo apoptosis as a mechanism of tumor growth suppression, but this critical control of apoptosis is lost as these lesions progress to carcinomas. These alterations in apoptosis occur during mammary tumor progression in mice containing wild-type p53(+/+) genotype as well as in mice with the p53(-/-) genotype. Thus, apoptosis in this tumor model occurs through a p53-independent mechanism. Because other studies have demonstrated p53-dependent apoptosis in T-AG-induced choroid plexus tumors of transgenic mice, we propose that the role of p53 in apoptosis may be tissue-specific. In addition, bcl-2 protein was not expressed in any mammary lesions. SV40 T-AG expression, which correlated with the nuclear p53 protein at all stages of tumor progression, was low in normal mammary epithelial cells, moderately high in atypical hyperplasias, and strongly expressed in adenocarcinomas. No p53 mutations were found at any stage of mammary adenocarcinoma development, suggesting that tumor progression does not require a dominantly acting p53 mutation in this transgenic model. p21(Waf1/Cip1) a cyclin-dependent kinase inhibitor, was expressed in normal mammary tissue but was not detected in the mammary carcinomas, despite high nuclear accumulation of wild-type p53 protein, suggesting functional loss of p53 due to binding of SV40 T-AG to p53. These findings suggest that suppression of apoptosis during the transition from atypical hyperplasia to adenocarcinoma appears to be a critical event for mammary cancer development in C3(1)/T-AG transgenic mice and occurs by p53- and bcl-2-independent pathways. C1 NCI,MOLEC ONCOL LAB,NIH,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,DIV BASIC SCI,OFF LAB ANIM SCI,FREDERICK,MD 21702. NCI,TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK,MD 21702. NR 40 TC 64 Z9 65 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1996 VL 56 IS 13 BP 2998 EP 3003 PG 6 WC Oncology SC Oncology GA UT398 UT WOS:A1996UT39800025 PM 8674054 ER PT J AU Beck, WT Grogan, TM Willman, CL CordonCardo, C Parham, DM Kuttesch, JF Andreeff, M Bates, SE Berard, CW Boyett, JM Brophy, NA Broxterman, HJ Chan, HSL Dalton, WS Dietel, M Fojo, AT Gascoyne, RD Head, D Houghton, PJ Srivastava, DK Lehnert, M Leith, CP Paietta, E Pavelic, ZP Rimsza, L Roninson, IB Sikic, BI Twentyman, PR Warnke, R Weinstein, R AF Beck, WT Grogan, TM Willman, CL CordonCardo, C Parham, DM Kuttesch, JF Andreeff, M Bates, SE Berard, CW Boyett, JM Brophy, NA Broxterman, HJ Chan, HSL Dalton, WS Dietel, M Fojo, AT Gascoyne, RD Head, D Houghton, PJ Srivastava, DK Lehnert, M Leith, CP Paietta, E Pavelic, ZP Rimsza, L Roninson, IB Sikic, BI Twentyman, PR Warnke, R Weinstein, R TI Methods to detect P-glycoprotein-associated multidrug resistance in patients tumors: Consensus recommendations SO CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; MDR1 GENE-EXPRESSION; CELL-LINES; MONOCLONAL-ANTIBODIES; DRUG-RESISTANCE; CLINICAL-TRIALS; TISSUES; MODULATION; EPITOPE; RNA AB Multidrug resistance (MDR), especially that associated with overexpression of MDR1 and its product, P-glycoprotein (Pgp), is thought to play a role in the outcome of therapy for some human tumors; however, a consensus conclusion has been difficult to reach, owing to the variable results published by different laboratories. Many factors appear to influence the detection of Pgp in clinical specimens, including its low and heterogeneous expression; conflicting definitions of detection end points; differences in methods of sample preparation, fixation, and analysis; use of immunological reagents with variable Pgp specificity and avidity and with different recognition epitopes; use of secondary reagents and chromogens; and differences in clinical end points. Also, mechanisms other than Pgp overexpression may contribute to clinical MDR. The combined effect of these factors is clearly important, especially among tumors with low expression of Pgp. Thus, a workshop was organized in Memphis, Tennessee, to promote the standardization of approaches to MDR1 and Pgp detection in clinical specimens. The 15 North American and European institutions that agreed to participate conducted three preworkshop trials with well-characterized MDR myeloma and carcinoma cell lines that expressed increasing amounts of Pgp. The intent was to establish standard materials and methods for a fourth trial, assays of Pgp and MDR1 in clinical specimens. The general conclusions emerging from these efforts led to a number of recommendations for future studies: (a) although detection of Pgp and MDR1 is at present likely to be more reliable in leukemias and lymphomas than in solid tumors, accurate measurement of low levels of Pgp expression under most conditions remains an elusive goal; (b) tissue-specific controls, antibody controls, and standardized MDR cell lines are essential for calibrating any detection method and for subsequent analyses of clinical samples; (c) use of two or more vendor-standardized anti-Pgp antibody reagents that recognize different epitopes improves the reliability of immunological defection of Pgp; (d) sample fixation and antigen preservation must be carefully controlled; (e) multiparameter analysis is useful in clinical assays of MDR1/Pgp expression; (f) immunostaining data are best reported as staining intensity and the percentage of positive cells; and (g) arbitrary minimal cutoff points for analysis compromise the reliability of conclusions. The recommendations made by workshop participants should enhance the quality of research on the role of Pgp in clinical MDR development and provide a paradigm for investigations of other drug resistance-associated proteins. C1 ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. UNIV ARIZONA, COLL MED, TUCSON, AZ 85274 USA. UNIV ARIZONA, ARIZONA CANC CTR, TUCSON, AZ 85274 USA. UNIV NEW MEXICO, ALBUQUERQUE, NM 87131 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. MD ANDERSON CANC CTR, HOUSTON, TX 77030 USA. NCI, MED BRANCH, BETHESDA, MD 20892 USA. STANFORD UNIV, MED CTR, STANFORD, CA 94305 USA. FREE UNIV AMSTERDAM HOSP, NL-1081 AMSTERDAM, NETHERLANDS. HOSP SICK CHILDREN, TORONTO, ON M5G 1X8, CANADA. HUMBOLDT UNIV BERLIN, CHARITE BERLIN, D-10117 BERLIN, GERMANY. MONTEFIORE MED CTR, ALBERT EINSTEIN CANC CTR, BRONX, NY 10467 USA. UNIV CINCINNATI, COLL MED, CINCINNATI, OH 45267 USA. UNIV ILLINOIS, COLL MED, CHICAGO, IL 60612 USA. UNIV CAMBRIDGE, CTR MRC, CAMBRIDGE CB2 2QH, ENGLAND. UNIV BRITISH COLUMBIA, VANCOUVER, BC V5Z 4E6, CANADA. KANTONSSPITAL, DEPT INTERNAL MED C, CH-9007 ST GALLEN, SWITZERLAND. FU NCI NIH HHS [CA-57639, CA-30103, CA-55164] NR 66 TC 351 Z9 357 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1996 VL 56 IS 13 BP 3010 EP 3020 PG 11 WC Oncology SC Oncology GA UT398 UT WOS:A1996UT39800027 PM 8674056 ER PT J AU Bani, MR Rak, J Adachi, D Wiltshire, R Trent, JM Kerbel, RS BenDavid, Y AF Bani, MR Rak, J Adachi, D Wiltshire, R Trent, JM Kerbel, RS BenDavid, Y TI Multiple features of advanced melanoma recapitulated in tumorigenic variants of early stage (radial growth phase) human melanoma cell lines: Evidence for a dominant phenotype SO CANCER RESEARCH LA English DT Article ID MALIGNANT-MELANOMA; TUMOR PROGRESSION; HUMAN MELANOCYTES; MURINE MELANOCYTES; INTEGRATION SITE; MOLECULAR-WEIGHT; EXPRESSION; INDUCTION; CANCER; TRANSFORMATION AB The vast majority of primary human cutaneous melanomas undergo a slow and gradual progression from a clinically indolent, curable radial growth phase (RGP) to a malignant vertical growth phase. We sought to develop a way of isolating genetically related malignant variants from a benign RGP human melanoma, called WM35. The parent and variants were then used as a model system to examine to what extent the expression of clinically and biologically relevant phenotypic features characteristic of advanced melanomas are associated with (and thus perhaps causative of) such a malignant conversion. Such a model system could also be used as a means of eventually identifying genetic alterations and cellular changes involved in the malignant switch in melanoma progression. To develop such a model, we subjected WM35 cells to retrovira insertional mutagenesis, which was followed by selection for progressive growth of solid tumors in nude mice. Highly aggressive and phenotypically stable tumorigenic variants were derived which contained at least four integrated proviruses. In contrast to the parental WM35 cells, these cell lines expressed several phenotypic features characteristic of naturally derived, advanced-stage malignant melanoma cells. Thus, in addition to tumor-forming ability in nude mice, the variants were growth factor and anchorage independent, overexpressed the MUC18 adhesion molecule, and lost responsiveness to the growth-inhibitory effect of several cytokines, including interleukin 6, transforming growth factor beta, interleukin 1 beta, and tumor necrosis factor-alpha. Tumorigenicity and ''multicytokine resistance'' were dominant traits since in somatic cell hybrids between the parental cells and a tumorigenic subline no suppressive effect of the former cell population was observed. These findings suggest that one or more dominantly acting genetic alterations might be involved in this progression of RGP melanoma cells. The identity of such alterations remains to be determined. C1 SUNNYBROOK HLTH SCI CTR,DIV CANC BIOL RES,TORONTO,ON 4N 3M5,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON M5S 1A1,CANADA. NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. FU NCI NIH HHS [CA 54908, CA 41233] NR 57 TC 46 Z9 46 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1996 VL 56 IS 13 BP 3075 EP 3086 PG 12 WC Oncology SC Oncology GA UT398 UT WOS:A1996UT39800036 PM 8674065 ER PT J AU Aebi, S KurdiHaidar, B Gordon, R Cenni, B Zheng, H Fink, D Christen, RD Boland, CR Koi, M Fishel, R Howell, SB AF Aebi, S KurdiHaidar, B Gordon, R Cenni, B Zheng, H Fink, D Christen, RD Boland, CR Koi, M Fishel, R Howell, SB TI Loss of DNA mismatch repair in acquired resistance to cisplatin SO CANCER RESEARCH LA English DT Article ID HUMAN OVARIAN-CARCINOMA; MAMMALIAN-CELLS; CIS-DIAMMINEDICHLOROPLATINUM(II); 6-THIOGUANINE; TOLERANCE; GUANINE; BINDING; CANCER; DAMAGE; TUMOR AB Selection of cells for resistance to cisplatin, a well-recognized mutagen, could result in mutations in genes involved in DNA mismatch repair and thereby to resistance to DNA-alkylating agents. Parental cells of the human ovarian adenocarcinoma cell line 2008 expressed hMLH1 when analyzed with immunoblot. One subline selected for resistance to cisplatin (2008/A) expressed no hMLH1, whereas another (2008/C13*5.25) expressed parental levels. Microsatellite instability was readily demonstrated in 2008/A cells but not in 2008 and in 2008/C13*5.25 cells. In addition, the 2008/A cells were 2-fold resistant to methyl-nitro-nitrosoguanidine and had a 65-fold elevated mutation rate at the HPRT locus as compared to 2008 cells, both of which are consistent with the loss of DNA mismatch repair in these cells. To determine whether the loss of DNA mismatch repair itself contributes to cisplatin resistance, studies were carried out in isogenic pairs of cell lines proficient or defective in this function. HCT116, a human colon cancer cell line deficient in hMLH1 function, was 2-fold resistant to cisplatin when compared to a subline complemented with chromosome 3 and expressing hMLH1. Similarly, the human endometrial cancer cell fine HEC59, which expresses no hMSH2, was 2-fold resistant to cisplatin when compared to a subline complemented with chromosome 2 that expresses hMSH2. Therefore, the selection of cells for resistance to cisplatin can result in the Loss of DNA mismatch repair, and loss of DNA mismatch repair in turn contributes to resistance to cisplatin. C1 UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. UNIV VERMONT,SCH MED,DEPT MICROBIOL & MOLEC GENET,BURLINGTON,VT 05405. RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014; Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 NR 40 TC 423 Z9 429 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1996 VL 56 IS 13 BP 3087 EP 3090 PG 4 WC Oncology SC Oncology GA UT398 UT WOS:A1996UT39800037 PM 8674066 ER PT J AU Gudas, JM Nguyen, H Li, T Sadzewicz, L Robey, R Wosikowksi, K Cowan, KH AF Gudas, JM Nguyen, H Li, T Sadzewicz, L Robey, R Wosikowksi, K Cowan, KH TI Drug-resistant breast cancer cells frequently retain expression of a functional wild-type p53 protein SO CARCINOGENESIS LA English DT Article ID TUMOR-SUPPRESSOR GENE; MOUSE DIHYDROFOLATE-REDUCTASE; MAMMARY EPITHELIAL-CELLS; CYCLE CHECKPOINT PATHWAY; DNA-DAMAGE; G(1) ARREST; CONSTITUTIVE EXPRESSION; P53-REGULATED PROTEIN; MULTIDRUG RESISTANCE; INDUCED APOPTOSIS AB Abnormalities in the p53 tumor suppressor gene have been shown to affect cellular processes related to cell cycle control and gene amplification, In this study we compare the status and function of wild-type p53 in MCF-7 breast cancer cells with sublines selected for resistance to chemotherapeutic agents having different mechanisms of action. Sublines that were resistant to melphalan, pyrazafurin, mitoxantrone, etoposide and PALA all retained expression of wild-type p53, Methotrexate-resistant MCF-7 cells were unusual heterozygotes that expressed a wild-type and dominant, in-frame p53 deletion mutant and the doxorubicin-resistant cells expressed only mutant p53, Analysis of the G1 checkpoint after treatment with ionizing radiation revealed that the pyrazafurin-, melphalan- and mitoxantrone-resistant cells arrested strongly in G1, The etoposide-and PALA-resistant cells had an intermediate G1 arrest phenotype and the methotrexate- and doxorubicin-resistant cells had a minimal G1 arrest phenotype. mRNA and protein analyses of downstream effector genes, including p21(CIP1/Waf1), mdm2, Gadd 45 and the retinoblastoma protein, did not entirely differentiate sublines having a strong versus intermediate G1 arrest phenotype, Neither the p53 status nor the strength of the G1 arrest could be correlated with cell survival after ionizing radiation, When drug-sensitive MCF-7 cells were treated with the same chemotherapeutic agents, p53 and p21(CIP1/Waf1) levels increased between 2-and 14-fold. Together these data suggest that other cellular factors likely play a role in overcoming the inhibitory effects of ionizing radiation on p53 in drug-resistant breast cancer cells. C1 NCI,MED BRANCH,DIV CANC TREATMENT,MED BREAST CANC SECT,BETHESDA,MD 20892. ONCOR MED,GAITHERSBURG,MD 20877. NR 94 TC 28 Z9 28 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1996 VL 17 IS 7 BP 1417 EP 1427 DI 10.1093/carcin/17.7.1417 PG 11 WC Oncology SC Oncology GA UY144 UT WOS:A1996UY14400004 PM 8706243 ER PT J AU Rao, KVN Detrisac, CJ Steele, VE Hawk, ET Kelloff, GJ McCormick, DL AF Rao, KVN Detrisac, CJ Steele, VE Hawk, ET Kelloff, GJ McCormick, DL TI Differential activity of aspirin, ketoprofen and sulindac as cancer chemopreventive agents in the mouse urinary bladder SO CARCINOGENESIS LA English DT Article ID RAT MAMMARY CARCINOGENESIS; COLON CANCER; INHIBITION; INDOMETHACIN; RISK; METABOLISM; SYNTHETASE; PIROXICAM; TUMORS; DRUG AB In vivo studies were conducted to compare the activity of three non-steroidal anti-inflammatory drugs as inhibitors of urinary bladder carcinogenesis induced in B6D2F(1) (BDF) mice by N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN), Mice received continuous dietary exposure to nontoxic doses of aspirin, sulindac or ketoprofen beginning 1 week prior to the first of eight weekly doses of 7.5 mg OH-BBN; studies were terminated at 24 weeks after the first carcinogen dose, Both dose levels of sulindac (200 and 400 mg/kg diet) and both dose levels of ketoprofen (40 and 80 mg/kg diet) reduced the incidence of transitional cell carcinoma of the urinary bladder by >70% from that seen in dietary controls, The high dose of sulindac conferred the greatest protection against bladder cancer induction, In contrast, when administered at 400 and 800 mg/kg diet aspirin was inactive as a chemopreventive agent in the OH-BBN/BDF bladder cancer model, The significant potency of sulindac and ketoprofen as inhibitors of urinary bladder carcinogenesis, when considered with their history of safe human use, suggests that these agents merit further study as drugs for cancer chemoprevention in this target tissue. C1 IIT,RES INST,DEPT LIFE SCI,CHICAGO,IL 60616. NCI,CHEMOPREVENT INVEST STUDIES BRANCH,BETHESDA,MD 20852. FU NCI NIH HHS [N01-CN-95151-07] NR 29 TC 79 Z9 84 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1996 VL 17 IS 7 BP 1435 EP 1438 DI 10.1093/carcin/17.7.1435 PG 4 WC Oncology SC Oncology GA UY144 UT WOS:A1996UY14400006 PM 8706245 ER PT J AU Marthaler, TM OMullane, DM Vrbic, V AF Marthaler, TM OMullane, DM Vrbic, V TI The Prevalence of Dental Caries in Europe 1990-1995 - ORCA Saturday Afternoon Symposium 1995 SO CARIES RESEARCH LA English DT Article DE caries prevalence; DMFT; dmft AB Caries prevalence data from recent studies in all European countries showed a general trend towards a further decline for children and adolescents. However, in several countries with already low caries prevalence in primary teeth, there was no further decrease. Regarding the permanent dentition, further reductions were observed in the 12-year age group, these being even more evident at the ages of 15-19 years. In some Central and Eastern European countries, caries prevalence in children and adolescents was still high. Few data were available on young adults, but the benefits of prevention are becoming manifest. The available data on the use of toothbrushes, fluorides and other pertinent items provided few clues as to the causes of the decline in caries prevalence. C1 NIDR, WASHINGTON, DC USA. UCL EASTMAN DENT HOSP, LONDON, ENGLAND. SCH DENT, NIJMEGEN, NETHERLANDS. ZENTRUM ZAHN MUND & KIEFERHEILKUNDE, ERFURT, GERMANY. DENT SCH & HOSP, CORK, IRELAND. WHO, COPENHAGEN, DENMARK. UNIV OSLO, FAC DENT, OSLO, NORWAY. UNIV LJUBLJANA, FAC MED, LJUBLJANA, SLOVENIA. RP Marthaler, TM (reprint author), UNIV ZURICH, INST DENT, CH-8028 ZURICH, SWITZERLAND. NR 28 TC 240 Z9 256 U1 0 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PD JUL-AUG PY 1996 VL 30 IS 4 BP 237 EP 255 PG 19 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UN229 UT WOS:A1996UN22900001 PM 8773416 ER PT J AU Giedd, JN Snell, JW Lange, N Rajapakse, JC Casey, BJ Kozuch, PL Vaituzis, AC Vauss, YC Hamburger, SD Kaysen, D Rapoport, JL AF Giedd, JN Snell, JW Lange, N Rajapakse, JC Casey, BJ Kozuch, PL Vaituzis, AC Vauss, YC Hamburger, SD Kaysen, D Rapoport, JL TI Quantitative magnetic resonance imaging of human brain development: Ages 4-18 SO CEREBRAL CORTEX LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER; CORPUS-CALLOSUM MORPHOLOGY; BASAL GANGLIA; MORPHOMETRIC ANALYSIS; TOURETTES-SYNDROME; SYNAPTIC DENSITY; CAUDATE-NUCLEUS; VISUAL-CORTEX; DYSLEXIA; MRI AB Brain magnetic resonance images (MRI) of 104 healthy children and adolescents, aged 4-18, showed significant effects of age and gender on brain morphometry. Males had larger cerebral (9%) and cerebellar (8%) volumes (P < 0.0001 and P = 0.008, respectively), which remained significant even after correction for height and weight. After adjusting for cerebral size, the putamen and globus pallidus remained larger in males, while relative caudate size was larger in females. Neither cerebral nor cerebellar volume changed significantly across this age range. Lateral ventricular volume increased significantly in males (trend for females), with males showing an increase in slope after age 11. In males only, caudate and putamen decreased with age (P = 0.007 and 0.05, respectively). The left lateral ventricles and putamen were significantly greater than the right (P = 0.01 and 0.0001, respectively). In contrast, the cerebral hemispheres and caudate showed a highly consistent right-greater-than-left asymmetry (P < 0.0001 for both). All volumes demonstrated a high degree of variability. These findings highlight gender-specific maturational changes of the developing brain and the need for large gender-matched samples in pediatric neuropsychiatric studies. C1 UNIV VIRGINIA,DEPT NEUROSURG,CHARLOTTESVILLE,VA 22903. NINCDS,BETHESDA,MD 20892. RP Giedd, JN (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; kozuch, patricia/0000-0002-7465-9671 NR 65 TC 671 Z9 677 U1 12 U2 44 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL-AUG PY 1996 VL 6 IS 4 BP 551 EP 560 DI 10.1093/cercor/6.4.551 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VA168 UT WOS:A1996VA16800001 PM 8670681 ER PT J AU McIntosh, AR Grady, CL Haxby, JV Ungerleider, LG Horwitz, B AF McIntosh, AR Grady, CL Haxby, JV Ungerleider, LG Horwitz, B TI Changes in limbic and prefrontal functional interactions in a working memory task for faces SO CEREBRAL CORTEX LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; HUMAN EXTRASTRIATE CORTEX; RHESUS-MONKEY; NETWORK ANALYSIS; HUMAN-BRAIN; PET IMAGES; PATHWAYS; CONNECTIONS; 2-DEOXYGLUCOSE AB Regional cerebral blood flow, measured with positron emission tomography, was used to identify brain regions that play a special role(s) in a working memory task for faces. Perceptual matching (no retention interval), short-delay (average = 3.5 s retention interval), intermediate-delay (average = 12.5 a), and long-delay (21 s) tasks were considered. From the idea that brain function is the result of neural interactions, the data were analyzed using anatomically based, covariance structural equation modeling. In perceptual matching, the dominant functional interactions were observed among the ventral cortical areas, from extrastriate regions, to the anterior temporal, and into the inferior prefrontal cortex. These interactions decreased with longer delay intervals. In the short-delay functional model, interactions along this ventral stream in the right hemisphere appeared to he rerouted through limbic areas with strong interactions among the hippocampal region, the anterior and posterior cingulate, and the inferior prefrontal cortices. For the intermediate-delay model, the hippocampocingulate interactions continued, but showed a shift to more left hemisphere involvement. In the long delay network, interactions within the right limbic circuit were reduced in favor of strong bilateral inferior prefrontal and frontocingulate interactions. Effects from the prefrontal cortex, especially from the left hemisphere, to temporal and occipito temporal cortices were particularly strong in the long delay model, suggesting recruitment of some of the same circuits primarily involved in face perception. The strong corticolimbic interactions at short and intermediate delays may represent maintenance of an iconic representation of the face during the retention interval. However, at longer delays, where the image was more difficult to maintain, a frontocingulate-occipital network was used that could represent an expanded encoding strategy resulting in a more resilient memory. C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. RP McIntosh, AR (reprint author), NIA,NEUROSCI LAB,BLDG 10,BETHESDA,MD 20892, USA. RI McIntosh, Anthony/G-4955-2011 NR 67 TC 116 Z9 116 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL-AUG PY 1996 VL 6 IS 4 BP 571 EP 584 DI 10.1093/cercor/6.4.571 PG 14 WC Neurosciences SC Neurosciences & Neurology GA VA168 UT WOS:A1996VA16800003 PM 8670683 ER PT J AU Merchant, K Chen, H Gonzalez, TC Keefer, LK Shaw, BR AF Merchant, K Chen, H Gonzalez, TC Keefer, LK Shaw, BR TI Deamination of single-stranded DNA cytosine residues in aerobic nitric oxide solution at micromolar total NO exposures SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ESCHERICHIA-COLI; HUMAN-CELLS; MUTATIONS; KINETICS; REPAIR; GLYCOSYLASE; NITROSATION; OXIDATION; NITRATE; AGENTS AB Deamination of cytosine to uracil is a potential source of mutations in DNA. Here we examine the deaminating ability of aerobic nitric oxide (NO) toward single-stranded DNA at very low (micromolar and below) total exposures, using a sensitive genetic method that allows us to study a single deamination event at a specific site in a 7200-nucleotide DNA molecule within a pool of ca. 100 000 other identical DNA molecules. We incubated gapped C141 M13mp2 DNA with the NO-generating compound, Et(2)N[N(O)NO]Na (DEA/NO), in aerobic buffer for 16 h to ensure complete autoxidation at pH 7.4 and 37 degrees C. After ultrafiltration to remove small molecules, the DNA was transformed into isogenic Escherichia coli cultures that were either deficient (NR9404, ung(-)) or proficient (MC1061, ung(+)) in uracil-DNA glycosylase activity. The gapped DNA was constructed such that the target (CCC) codon was contained in a short single-stranded segment of otherwise double-stranded circular DNA, and the incubation was performed in a closed system to prevent loss of NO to the atmosphere before the reaction was complete. An increase in the reversion frequency in the ung(-) strain was noted between 0 and 1 mu M DEA/NO, and the reversion frequency leveled out between 3 and 30 mu M. However, 30 mu M ''spent'' DEA/NO (i.e., that which was similarly incubated for 4 h to complete the autoxidation of NO before the DNA was added) did not increase reversion frequency relative to control. Nearly all (42/43) of the mutations identified after 1 mu M DEA/NO treatment were C --> T transitions, and reversion frequency in the isogenic ung(+) strain was lower than in the ung(-) strain. The data are consistent with the hypothesis that total NO exposures in the mu mol/L range can lead to C --> T mutations via a mechanism most probably involving deamination of DNA cytosine residues. C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21708. RP Merchant, K (reprint author), DUKE UNIV,PM GROSS CHEM LAB,DURHAM,NC 27708, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [5RO1-CA-44709] NR 43 TC 23 Z9 23 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL-AUG PY 1996 VL 9 IS 5 BP 891 EP 896 DI 10.1021/tx950102g PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA UY227 UT WOS:A1996UY22700013 PM 8828926 ER PT J AU Chute, JP Kelley, MJ Venzon, D Williams, J Roberts, AH Johnson, BE AF Chute, JP Kelley, MJ Venzon, D Williams, J Roberts, AH Johnson, BE TI Retreatment of patients surviving cancer-free 2 or more years after initial treatment of small cell lung cancer SO CHEST LA English DT Article DE carcinoma; lung neoplasm; recurrence; small cell; survivors; treatment outcome ID SOUTHWEST-ONCOLOGY-GROUP; LONG-TERM SURVIVAL; COMBINATION CHEMOTHERAPY; BRONCHOGENIC-CARCINOMA; RADIATION-THERAPY; RADIOTHERAPY; 2ND; RELAPSE; DISEASE AB Study objective: To assess the outcome after retreatment of patients with small cell lung cancer (SCLC) who redevelop small cell cancer (SCC) 2 or more years after initial therapy. Design: Retrospective analysis. Setting: Single government institution: the National Cancer Institute. Patients: Twenty patients who redeveloped SCC among 65 patients who survived 2 or more years after starting treatment for their initial cancer. Measurements: The response rate of patients after retreatment, the survival duration from the time of redevelopment of SCC, and the toxicities of retreatment. Results: Twenty patients redeveloped SCC: 18 with a relapse and 2 with a second primary cancer, Sixteen received treatment after they redeveloped SCLC while four did not. Eleven patients were retreated with chemotherapy alone, two patients received chemotherapy plus chest radiotherapy, one patient received radiotherapy alone, one patient underwent lobectomy, and one patient was treated with a monoclonal antibody followed by chemotherapy, Nine of 16 patients (56%) treated after they redeveloped SCLC had an objective response (3 complete and 6 partial), The median survival of all 20 patients after they redeveloped SCC was 3.9 months (range, 0 to 46 months), The median survival of the patients who were retreated was 6.5 months (range, 1 to 46 months). Conclusions: Patients who suffer relapses with SCLC 2 or more years from diagnosis are candidates for retreatment. C1 NCI, NAVY MED ONCOL BRANCH, NATL NAVAL MED CTR, BETHESDA, MD 20889 USA. NCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT PATHOL, BETHESDA, MD USA. NATL NAVAL MED CTR, DEPT MED, BETHESDA, MD USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. RI Venzon, David/B-3078-2008 NR 32 TC 19 Z9 20 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1996 VL 110 IS 1 BP 165 EP 171 DI 10.1378/chest.110.1.165 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA UY854 UT WOS:A1996UY85400033 PM 8681622 ER PT J AU Owens, LM Fralix, TA Murphy, E Cascio, WE Gettes, LS AF Owens, LM Fralix, TA Murphy, E Cascio, WE Gettes, LS TI Correlation of ischemia-induced extracellular and intracellular ion changes to cell-to-cell electrical uncoupling in isolated blood-perfused rabbit hearts SO CIRCULATION LA English DT Article DE ischemia; cells; electrical stimulation ID CYTOSOLIC FREE CALCIUM; MYOCARDIAL ISCHEMIA; JUNCTIONAL CONDUCTANCE; GUINEA-PIG; RAT-HEART; F-19 NMR; K+; POTASSIUM; MUSCLE; H+ AB Background The relationships between the metabolic, ionic, and electrical changes of acute ischemia have not been determined precisely because they have been studied under different experimental conditions. We used ion-selective electrodes, nu clear magnetic resonance spectroscopy, and the four-electrode method to perform four series of experiments in the isolated blood-perfused rabbit heart loaded with 5F-BAPTA during 30 to 35 minutes of no-flow ischemia. We sought to determine the relationship between changes in phosphocreatine (PCr), adenosine triphosphate (ATP), intracellular calcium ([Ca2+](i)), intracellular pH (pH(i)), extracellular potassium ([K+](e)), extracellular pH (pH(c)), and whole-tissue resistance (r(t)). Methods and Results In the first 8 minutes of ischemia, [K+](e) rose from 4.9 to 10.8 mmol/L, PCr fell by 90%, ATP decreased by 25%, and pH(i) and pH(e), decreased by 0.5 U, while [Ca2+](i) and r(t) changed only slightly. Between 8 and 23 minutes, [K+](e) changed only slightly; pH(i), pH(e). and ATP continued to fall, and [Ca2+](i) rose. r(t) did not increase until > 20 minutes of ischemia, when pH(i) was < 6.0 and [Ca2+](i) had increased more than threefold. The increase in r(t), indicating electrical uncoupling, coincided with the third phase of the [K+](e) change. Conclusions Our study suggests that cellular uncoupling oc curs only after a significant rise in [Ca2+](i) and fall in pH(i) and that these ionic and electrical changes can be identified by the change in [K+](e). Our study underscores the importance of using a common model while attempting to formulate an integrated picture of the ionic, metabolic, and electrical events that occur during acute ischemia. C1 UNIV N CAROLINA,SCH MED,DIV CARDIOL,CHAPEL HILL,NC 27599. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. FU NHLBI NIH HHS [5-R-37-HL-38885, 5-PO1-HL-27430] NR 29 TC 45 Z9 48 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 1 PY 1996 VL 94 IS 1 BP 10 EP 13 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UU208 UT WOS:A1996UU20800003 PM 8964108 ER PT J AU Moss, MW Carella, AV Provost, V Quinn, TC AF Moss, MW Carella, AV Provost, V Quinn, TC TI Comparison of absolute CD4(+) lymphocyte counts determined by enzyme immunoassay (TRAx CD4 test kit) and flow cytometry SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID INFECTION AB Currently, CD4(+) lymphocyte counts are one of the most widely used surrogate markers for monitoring disease progression in and initiating therapy for human immunodeficiency virus-infected individuals, However, the process of obtaining lymphocyte subset counts can be complex and expensive, often rendering the test inaccessible to many patients, In contrast to standard laser-based flow cytometry, the TRAx CD4 Test Kit utilizes an enzyme-linked immunoassay format to provide CD4(+) lymphocyte counts by a simple and more cost-effective means. In order to evaluate the utility of the TRAx CD4(+) assay in comparison,vith flow cytometry, heparinized blood samples were drawn from 188 infected and uninfected adult patients and 24 infected pediatric patients and evaluated by both assays. The correlation coefficient for all adult individuals tested was 0.94, and the mean absolute counts (in cells per milliliter, +/- standard deviation) were 510 +/- 358 for TRAx and 480 +/- 361 for how cytometry, The correlation for the pediatric group was 0.93, with mean absolute counts of 956 +/- 767 for TRAx and 1,521 +/- 1,438 for flow cytometry. Overall the TRAx CD4 Test Kit performed well in comparison to flow cytometry, and its lower cost and ease of use make it an encouraging alternative for the routine determination of CD4(+) lymphocyte counts. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 10 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUL PY 1996 VL 3 IS 4 BP 371 EP 373 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UV503 UT WOS:A1996UV50300002 PM 8807198 ER PT J AU Kelley, MJ Nakagawa, K Conrad, NK LeRiche, J Murray, N Lee, JS Ro, JY Shaw, EG Tucker, MA Johnson, BE AF Kelley, MJ Nakagawa, K Conrad, NK LeRiche, J Murray, N Lee, JS Ro, JY Shaw, EG Tucker, MA Johnson, BE TI Genetic analysis of second primary lung cancers in patients surviving small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID P53; MUTATIONS AB We performed genetic analysis on 12 second primary non-small cell lung cancers in patients surviving small cell lung cancer to assess the potential contribution of smoking to the development of these tumors, Mutations of TP53 were found in three (25%) tumors, KRAS2 in three (25%) tumors, and CDKN2 in two (18%) tumors, Four (50%) mutations (one each in TP53 and CDKN2 and two in KRAS2) were G:C to T:A transversions on the coding strand, a mutation accounting for approximately one-third of mutations in smoking-related tumors but uncommonly found in lung cancers not associated with smoking, The genetic changes in these second lung cancers are more representative of smoking-associated malignancies than lung cancers arising in patients occupationally exposed to irradiation and atomic bomb survivors. C1 NCI,BETHESDA,MD 20889. BRITISH COLUMBIA CANC AGCY,VANCOUVER,BC V5Z 4E6,CANADA. MD ANDERSON CANCER CTR,HOUSTON,TX 77030. MAYO CLIN,ROCHESTER,MN 55905. RP Kelley, MJ (reprint author), NCI,NAVY MED ONCOL BRANCH,BLDG 8,ROOM 5101,8901 ROCKVILLE PIKE,BETHESDA,MD 20889, USA. RI Tucker, Margaret/B-4297-2015; OI Kelley, Michael/0000-0001-9523-6080 NR 13 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1996 VL 2 IS 7 BP 1103 EP 1105 PG 3 WC Oncology SC Oncology GA UV854 UT WOS:A1996UV85400003 PM 9816274 ER PT J AU Carter, CA Wand, WR Li, LH DeKoning, TF McGovren, JP Plowman, J AF Carter, CA Wand, WR Li, LH DeKoning, TF McGovren, JP Plowman, J TI Preclinical antitumor activity of bizelesin in mice SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA-SEQUENCE SPECIFICITY; RESISTANT P388 LEUKEMIA; CC-1065 NSC-298223; BIOLOGICAL-ACTIVITY; TUMOR XENOGRAFTS; CROSS-LINKING; CELL-LINES; ANALOGS; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; O6-BENZYLGUANINE AB Bizelesin (U-77779, NSC 615291), a synthetic analogue of the cytotoxic antibiotic CC-1065, is a bifunctional alkylating agent that produces DNA interstrand cross-links, Bizelesin was evaluated for antitumor activity against a broad spectrum of syngeneic murine tumors and human tumor xenografts in mice, Systemic drug administration produced >6.7 log(10) cell kill against i.p. implanted P388 and L1210 leukemias and 80% tumor-free survivors against s.c. implanted L1210. Against i.p. implanted B16 melanoma: i.p. drug administration produced a 158% increase in life span with 25% tumor-free survivors, whereas i.v. drug administration produced only a 67% increase in life span with no tumor-free survivors, More than 1.0 log(10) cell kill was observed at low mu g/kg doses in several human tumor models representing diverse histiotypes (CAKI-1 renal, LX-1 lung, HT-29 colon, LOX IMVI and UACC-62 melanomas, and MX-1 mammary), Less than 1.0 log(10) cell kill was exhibited in other tumor models (Lewis lung, colon 38, pancreatic 02, MCF7 mammary, and SK-MEL-3 melanoma), Bizelesin was optimally active when administered i.v. Although antitumor activity was independent of the schedule of administration, greater total doses were tolerated on the more prolonged schedules in any given experiment, Therapeutic doses of bizelesin did not produce delayed deaths, which had previously been observed for the parent compound CC-1065, However, recovery of lost weight was not attained until 16-30 days posttherapy, Bizelesin was as active against murine leukemia sublines resistant to cisplatin, melphalan, and 1,3-bis-(2-chloroethyl)-1-nitrosourea as against the parental line but was totally inactive against a doxorubicin-resistant subline, The complete cross-resistance of the doxorubicin-resistant subline to bizelesin suggests that bizelesin may be a substrate for the efflux pump that causes multidrug resistance, Due to its breadth of antitumor activity, potency, unique mechanism of action, and lack of cross-resistance with other alkylating agents, bizelesin was selected for development in clinical trials by the National Cancer Institute and the Upjohn Company, Toxicological studies and pharmaceutical development have been completed, and clinical trials are planned to start in the summer of 1996. C1 UPJOHN CO,KALAMAZOO,MI 49001. NCI,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,FREDERICK,MD 21701. RP Carter, CA (reprint author), SO RES INST,DEPT EXPTL THERAPEUT,POB 55305,BIRMINGHAM,AL 35255, USA. NR 27 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 1996 VL 2 IS 7 BP 1143 EP 1149 PG 7 WC Oncology SC Oncology GA UV854 UT WOS:A1996UV85400009 PM 9816280 ER PT J AU TreiberHeld, S Stewart, DM Barraclough, HA Kurman, CC Nelson, DL AF TreiberHeld, S Stewart, DM Barraclough, HA Kurman, CC Nelson, DL TI Release of sIL-2R alpha from and activation of native human peripheral blood mononuclear cells by recombinant IL-15 SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID INTERLEUKIN-2 RECEPTOR; ANTIBODY AB The cytokine interleukin (IL)-15 shares several activities with IL-2. Both cytokines induced expression of cell-surface IL-2R alpha (CD25) on freshly isolated human peripheral blood mononuclear cells (PBMC) in the absence of other exogenous stimuli. They also stimulated the release of soluble IL-2R alpha and induced proliferation of these cells in 1-week cultures in a time-and dose-dependent manner. Recombinant IL-7 could also induce the expression of CD25, although sIL-2R alpha was released at only low levels. In monocyte-depleted PBMC the sIL-2R alpha release was minimal. When isolated T cells or non-T cells were stimulated by rIL-15 or rIL-2, cell surface CD25 was expressed, but released sIL-2R alpha was undetectable. On stimulation with rIL-15, more than 80% of all natural killer cells expressed CD25 and more CD8(br+) lymphocytes were positive for CD25 compared to stimulation by rIL-2. These results may be clinically relevant because several diseases are associated with high serum levels of sIL-2R alpha which may be not only due to IL-2 but also due to IL-15 stimulation. (C) 1996 Academic Press, Inc. RP TreiberHeld, S (reprint author), NCI,IMMUNOPHYSIOL SECT,METAB BRANCH,NIH,BETHESDA,MD 20892, USA. NR 14 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD JUL PY 1996 VL 80 IS 1 BP 67 EP 75 DI 10.1006/clin.1996.0095 PG 9 WC Immunology; Pathology SC Immunology; Pathology GA UU007 UT WOS:A1996UU00700010 PM 8674241 ER EF